A smart process controller framework for Industry 4.0 settings

This paper presents a smart supervisory framework for a single process controller, designed for Industry 4.0 shop floors. This digitization of a full supervisory suite for a single process controller enables self-awareness, self-diagnosis, self-prognosis, and self-healing (by definition, these "self" elements are missing from other supervisory frameworks diagnosing numerous controllers in parallel). The proposed framework is aligned with the concept of a Cyber Physical System (CPS), since its implementation generates a rich cyber physical entity of the controlled process. This CPS entity can either be considered as the process digital twin, or can provide a solid basis for generating it. Finally, the framework includes the main characteristics of Industry 4.0, such as advanced use of Artificial Intelligence (AI) and big data analysis. The framework is based on four modules: (1) Control and Awareness module—performing both continuous process control and adjustments, as well as machine learning (ML) and statistical process control (SPC) for identifying abnormalities that require further diagnosis; (2) Process -diagnosis module—performing continual (recurrent) analysis of the process state and trends; (3) Prognosis and Healing module—performing prognosis and automated intervention via parameter changes, re-configurations, and automated maintenance; (4) External Interaction Platform—an interactive module for interfacing with experts, presenting them with the process analysis information and obtaining feedback from them as part of a learning process. Using an implementation showcase to illustrate the methodological framework’s applicability, we demonstrate its real-world potential. The proposed framework could serve as a guide for implementing smart process control and maintenance systems in Industry 4.0 shop floors. It could also provide a firm basis for comparison with future suggested frameworks. Future research directions could include pursuing improvements to the proposed process control framework and validating the framework by case studies of its implementation.

     

Effect of Freezer Programs on Real-Time Storage Results of Dissolution Profiles

Carstensen and Rhodes¹ have suggested that when, in stability programs, assays cannot be performed immediately after the protocol-designated storage time, then freezing them until such a time when assays can be performed would be a reasonable manner to retain the protocol schedule. They caution, however, that such a procedure may not be valid for dissolution data. The article to follow deals with real-time data showing that such a process is feasible for Nalidixic Acid tablets (and presumably for other tablets as well), and that, furthermore, the dissolution pattern would seem to be “frozen” as well.     

The band areas of proteins determined by fluorescent scanning in the commercial automated gel electrophoresis apparatus

An automated gel electrophoresis apparatus, recently available commercially, allows one to follow the band during electrophoresis in real time, and lends itself therefore to an evaluation of bandwidth as a function of migration time (the dispersion coefficient), resolution and band shape. These determinations assume the constancy of band area with migration time and at various gel concentrations. The purpose of the present study was to verify these assumptions. Representative proteins and sodium dodecyl sulfate (SDS)-proteins, either natively fluorescent or fluorescein carboxylate labeled, were found to exhibit band areas which approach constancy as a function of migration time in both agarose and polyacrylamide gel electrophoresis, provided that (i) the protein concentration under the band was low enough to obviate self-quenching of fluorescence; (ii) the separation of the protein of interest from contaminants had progressed sufficiently during the time at which band areas were measured; (iii) the baseline under the peak was sufficiently well defined. However, band areas decrease with increasing gel concentration. Protein peaks exhibited leading and trailing tails. The ratio of the combined tail area to total area appeared to be near-constant at varying migration times. However, that ratio increases with increasing gel concentration. The tail area does not appear to be an artifact of fluorometric detection since it is reproduced upon fluorimetric analysis of the protein eluted from gel slices after electrophoresis. However, it may be due to photochemical destruction under the conditions of repetitive fluorometric peak detection.     

Engagement of T cell receptor triggers its recruitment to low-density detergent-insoluble membrane domains

T-cell receptors (TCRs) upon binding to peptide-MHC ligands transduce signals in T lymphocytes. Tyrosine phosphorylations in the cytoplasmic domains of the CD3 (gammadeltaepsilon) and zeta subunits of the TCR complex by Src family kinases initiate the signaling cascades via docking and activation of ZAP-70 kinase and other signaling components. We examined the role of the low-density detergent-insoluble membranes (DIMs) in TCR signaling. Using mouse thymocytes as a model, we characterized the structural organization of DIMs in detail. We then demonstrated that TCR engagement triggered an immediate increase in the amount of TCR/CD3 present in DIMs, which directly involves the engaged receptor complexes. TCR/CD3 recruitment is accompanied by the accumulation of a series of prominent tyrosine-phosphorylated substrates and by an increase of the Lck activity in DIMs. Upon TCR stimulation, the DIM-associated receptor complexes are highly enriched in the hyperphosphorylated p23 zeta chains, contain most of the TCR/CD3-associated, phosphorylation-activated ZAP-70 kinases and seem to integrate into higher order, multiple tyrosine-phosphorylated substrate-containing protein complexes. The TCR/CD3 recruitment was found to depend on the activity of Src family kinases. We thus provide the first demonstration of recuitment of TCR/CD3 to DIMs upon receptor stimulation and propose it as a mechanism whereby TCR engagement is coupled to downstream signaling cascades.     

Modeling of precipitation hardening in Mg-based alloys

This work deals with the development of Mg-based alloys with enhanced properties at elevated temperatures. This is achieved by precipitation of binary phases such as MgZn₂ and Mg₂Sn during the aging of these alloys. The aim of the present work is to develop and calibrate a model for precipitation hardening in Mg-based alloys, as different types of precipitates form simultaneously. The modified Langer-Schwartz approach, while taking into account nucleation, growth and coarsening of the new phase precipitations, was used for the analysis of precipitates’ evolution and precipitation hardening during aging of Mg-based alloys. Two strengthening mechanisms associated with particle-dislocation interaction (shearing and bypassing) were considered to be operating simultaneously due to particle size-distribution. Parameters of the model, R _N i and k _{σ i} , were found by fitting of calculated densities and average sizes of precipitates with ones estimated from experiments. The effective diffusion coefficients of phase formation processes, which determine the strengthening kinetics, were estimated from the hardness maximum positions on the aging curves.     

High affinity presentation of an autoantigenic peptide in type I diabetes by an HLA class II protein encoded in a haplotype protecting from disease

Tissue composition and the distribution of body mass are described for four genera of East African Bovidae (Madoqua, Gazella, Damaliscus, Hippotragus) with supporting data from four others (Neotragus, Oryx, Tragelaphus, Connochaetes). These species are high in muscle mass, an adaptation convergent with other high-speed terrestrial cursors, bounders, and saltators. The segments below the elbow/cubitus and knee/stifle/genu joints in small bovids are both lighter in percent of total body mass (8.6% TBM) and less heavily muscled (10-15% of total limb musculature) than those segments in macaques (13.6% TBM, 20-25% of the limb musculature). Bovid species differ from one another in the regional distribution of muscle mass. Madoqua kirkii (4-5 kg) concentrates muscle in the lumbar extensors and hindlimbs; large species such as Damaliscus doreas (50-60 kg) and Hippotragus niger (160-220 kg) distribute it more evenly between the lumbar and cervical regions and between the hindlimbs and forelimbs. Gazella dorcas (10-20 kg) is quantitatively intermediate in those characteristics. The redistribution of muscle mass with increasing size correlates with the loss of axial bending of the vertebral column: in small, hindlimb dominant, 'dorsomobile' species such as Madoqua sagittal mobility increases stride length through 'extended' suspension; in large 'dorsostable' species such as Damaliscus and Hippotragus the vertebral column resists bending, consequently abbreviating or omitting this non-contact phase of the gait cycle. Locomotor adaptation as it is reflected in size, shape, and musculoskeletal structure is the key to habitat choice, dietary specialization, social structure, and male agonistic behavior and, therefore, central to the fabric of behavioral ecology.     

Generalization of the Gram-Charlier/Edgeworth Series and Application to Time-Frequency Analysis

We derive a general equation relating probability densities and as special cases we the obtain Gram-Charlier and Edgeworth series. This allows us to generalize these methods and clarify a number of issues pertaining to both probability theory and time-frequency analysis. In particular we show how the Gram-Charlier and Edgeworth series are related to the kernel method of time-frequency analysis. The approach allows us to construct densities that satisfy given constraints such as joint moments or conditional moments. Also, we show that the kernel has to be signal dependent and that to obtain a proper distribution it should be the ratio of two characteristic functions.     

Phase I study of mitoxantrone plus etoposide with multidrug blockade by SDZ PSC-833 in relapsed or refractory acute myelogenous leukemia

PURPOSE: Expression of the multidrug resistance gene (MDR1) p170 protein is frequent in leukemic blasts from patients with relapsed acute myelogenous leukemia (AML). A phase I study using the nonimmunosuppressive MDR1 blocker SDZ PSC-833 (PSC) in combination with mitoxantrone (MITO) and etoposide (VP) was performed. PATIENTS AND METHODS: Starting doses (LVL0) of MITO (3.25 mg/m2/d on days 1 and 3 to 6) and VP (210 mg/m2/d on days 1 and 3 to 5) were 40% of the maximal-tolerated dose (MTD) from a prior study. A 1.5-mg/kg loading dose of PSC was followed by a 120-hour continuous infusion of 10 mg/kg/d on days 2 to 6. Blood samples for PSC, MITO, and VP pharmacokinetics (PK) were taken on days 1 and 3, and samples for MDR1 expression were taken on day 0. RESULTS: Severe mucositis developed in all patients at LVL0; therefore, MITO and VP doses were reduced to 2.5 and 170 mg/m2 (LVL-1) for the next seven patients, and this dose proved to be MTD. All LVL0 and three LVL-1 patients had transient elevations in the serum bilirubin level to > or = 4 mg/dL. Serum creatinine level increased to greater than 2 mg/dL in one case. There were no other grade 3 or 4 nonhematologic toxicities observed. The peripheral blood was cleared of leukemia in three LVL0 and four LVL-1 patients. The marrow was cleared of leukemic cells in one LVL0 and five LVL-1 patients, and a significant reduction in marrow leukemic infiltrate was observed in eight of 10. No patient achieved complete remission (CR), and all died of progressive disease (n = 8) or infection (n = 2). MDR1 expression was detected by fluorescent-activated cell sorter (FACS) analysis in five of seven cases. An elevated MDR1 mRNA level was detected by quantitative polymerase chain reaction (Q-PCR) in six of eight cases studied. Clearing of leukemia cells from the marrow occurred in four of six MDR1-positive and one of three MDR1-negative patients. Despite the fact that LVL0 doses had to be reduced due to toxicity, coadministration of PSC did not produce a consistent effect on MITO PK; however, it did repeatedly lead to increased levels of VP in the serum. CONCLUSION: We conclude that PSC-MITO-VP is a tolerable regimen with antileukemic activity. Addition of PSC necessitated a 66% reduction in MITO and VP doses from a prior study without PSC.     

Managing network security — Part 6: Computer games and network security management

Over the last few years, computing has changed to an almost purely networked environment, but the technical aspects of information protection have not kept up. As a result, the success of information security programmes has increasingly become a function of our ability to make prudent management decisions about organizational activities. This series of articles takes a management view of protection and seeks to reconcile the need for security with the limitations of technology.