Industry 4.0: a supply chain innovation perspective

The Fourth Industrial Revolution – also known as Industry 4.0 (i4.0) – comprises the digitalisation of the industrial sector. This paper uses the theoretical lens of supply chain innovation (SCI) to investigate the implications of i4.0 on supply chain management. For these purposes, the method of structured content analysis is applied to more than 200 use cases of i4.0-enabled SCI introduced by both established and startup companies. i4.0-enabled SCI manifests along three dimensions: process, technology, and business architecture. The key findings of this study can be summarised as follows: first, i4.0-enabled SCI extends the initial focus on productivity improvements in SC processes towards scalability and flexibility. Second, extant i4.0 solutions rely mostly on analytics and smart things while omitting smart people technology and the human-centric approach associated with the i4.0 paradigm. Third, established companies adopt i4.0 merely to sustain their existing business architectures while startup companies radically change their operating models, relying heavily on data analytics and the platform economy. Consequently, established companies pursue a problem-driven, engineering-based approach to SCI while startup companies follow an ‘asset-light’, business-driven approach. Lastly, there are two distinct approaches to digitalising operational SC processes: platform-based crowdsourcing of standard processes and on-demand provision of customised services.     

Polymeric prodrugs of mitomycin C designed for tumour tropism and sustained activation

Prodrugs of mitomycin C (MMC) based on soluble poly-[N-(2-hydroxyethyl)-L-glutamine] (pHEG) polymers have been evaluated as tumour-targeted drugs. These materials are designed to exploit the enhanced permeability of tumour vasculature, combining a passive tumour tropism with decreased systemic liberation of free MMC. A tri- or tetrapeptide linkage (e.g. Gly-Phe-Ala-Leu) between pHEG and the aziridine nitrogen of MMC can combine good hydrolytic stability with rapid cleavage by lysosomal enzymes, releasing free MMC. The conjugates showed decreased systemic toxicity and could be administered to mice at a total MMC dose of 15 mg/kg i.v., compared with just 6 mg/kg for free MMC. Conjugates also showed better activity against animal models of established tumours, achieving up to 77% increased life span (ILS) against solid P388 leukaemia, compared with only 23% for free MMC, and up to 121% ILS against solid C26 colorectal carcinoma, compared with no activity for the free drug. Improving the therapeutic index of anticancer drugs by combining tumour tropism with decreased systemic toxicity is a versatile approach that should produce a new generation of improved anticancer agents.     

Introduction of a nonlinearity measure for principal component models

Although principal component analysis (PCA) is an important tool in standard multivariate data analysis, little interest has been devoted to assessing whether the underlying relationship within a given variable set can be described by a linear PCA model or whether nonlinear PCA must be utilized. This paper addresses this deficiency by introducing a nonlinearity measure for principal component models. The measure is based on the following two principles: (i) the range of recorded process operation is divided into smaller regions; and (ii) accuracy bounds are determined for the sum of the discarded eigenvalues. If this sum is within the accuracy bounds for each region, the process is assumed to be linear and vice versa. This procedure is automated through the use of cross-validation. Finally, the paper shows the utility of the new nonlinearity measure using two simulation studies and with data from an industrial melter process.     

Cr-Mo solid solutions forced by high-energy ball milling

Mixtures of Cr and Mo elemental powders, with the nominal compositions Cr₂₅Mo₇₅, Cr₅₀Mo₅₀, and Cr₇₅Mo₂₅, are processed by high-energy ball milling at ambient temperature. Milling is observed to force the mixing of the immiscible bcc elements Cr and Mo into solid solutions. The lattice parameter of these solid solutions, measured by X-ray diffraction (XRD), displays the expected positive deviation from Vegard’s law. These deviations are compared to the ones predicted by Eshelby’s inclusion model for dilute alloys. The conventional Williamson-Hall approach is shown to fail to determine the grain size in as-milled samples, probably due to the high density of dislocations. Annealing at 700 °C for 10 hours under argon leads to a large reduction in structural defect density, without inducing any significant decomposition. The mixing measured in Cr-Mo is discussed in the broader context of the mechanical mixing forced by ball milling in moderately immiscible systems.     

Metastasis induced by overexpression of p185neu-T after orthotopic injection into a prostatic epithelial cell line (NbE)

The effects of the composition of bacteriological growth media on the light output in a chemiluminometric assay of beta-galactosidase in Escherichia coli using 1,2-dioxetane substrates has been studied. In this assay a basic conflict exists between conditions that promote optimal bacterial growth and those conducive to maximal chemiluminescence. Common medium ingredients such as yeast or beef extract, protein hydrolysates and lactose suppress light emission and/or lead to high backgrounds. Quenching of light emission is probably partly due to light absorption by medium ingredients such as oxgall, and partly to interference with the reaction triggering the chemiluminescent process. Elevated backgrounds are caused by the presence of high concentrations of protein hydrolysates, which interact with the alkali in the accelerator solution. Only two purposely developed media, i.e. ILM and Colicult are shown to reconcile the requirements of growth support with that of optimal luminescent properties.     

Interdiffusion behavior of Hg in HgTe/CdTe superlattices grown on Cd0.96Zn0.04 Te (211)B substrates by molecular beam epitaxy

Double-crystal x-ray rocking curve (DCRC) and secondary-ion mass-spectroscopy (SIMS) measurements have been performed to investigate the effect of rapid thermal annealing on the interdiffusion behavior of Hg in HgTe/CdTe superlattices grown on Cd_0.96Zn_0.04Te (211)B substrates by molecular beam epitaxy. The sharp satellite peaks of the DCRC measurements on a 100-period HgTe/CdTe (100Å/100Å) superlattice show a periodic arrangement of the superlattice with high-quality interfaces. The negative direction of the entropy change obtained from the diffusion coefficients as a function of the reciprocal of the temperature after RTA indicates that the Hg diffusion for the annealed HgTe/CdTe superlattice is caused by an interstitial mechanism. The Cd and the Hg concentration profiles near the annealed HgTe/CdTe superlattice interfaces, as measured by SIMS, show a nonlinear behavior for Hg, originating from the interstitial diffusion mechanism of the Hg composition. These results indicate that a nonlinear interdiffusion behavior is dominant for HgTe/CdTe superlattices annealed at 190°C and that the rectangular shape of HgTe/CdTe superlattices may change to a parabolic shape because of the intermixing of Hg and Cd due to the thermal treatment.     

The spinal muscular atrophy gene region at 5q13.1 has a paralogous chromosomal region at 6p21.3

We have examined acetaminophen (paracetamol) dosing for outpatient management of posttonsillectomy pain in children. Forty children, 5-15 years of age, undergoing tonsillectomy and their parents were randomly assigned to use a scheduled administration of acetaminophen in weight appropriate doses, 60 mg.kg-1.24h-1 orally, 90 mg.kg-1.24h-1 rectally, or to use acetaminophen 'as needed' according to present standards (control group). Postoperative pain was assessed by the child using the poker chip tool for the first three days after discharge. The prevalence of pain amongst all the children was high. The second day after discharge 22%-64% of the children in the study group and 36%-73% of the children in the control group rated severe pain. Recommended dose ranges of acetaminophen do not provide sufficient pain relief in children following tonsillectomy. Further studies are required to determine, whether higher doses of acetaminophen or analgesics with different analgesic properties will lead to improved analgesia in children following tonsillectomy.     

Measurement of Energy Expenditure in Elite Athletes Using MEMS-Based Triaxial Accelerometers

Fitness development and performance assessment of elite athletes requires an understanding of many physiological factors, many of these are direct and indirect measures of athlete energy expenditure. Many methods are physiological factor assessments and require the athlete to be constrained by laboratory equipment or periodic interruption of activity to take measurements such as blood samples are required to be taken. This paper presents a method that is entirely ambulatory and noninvasive, using microelectromechanical systems (MEMS) accelerometers. The commonly used output of commercial accelerometer-based devices (known as "counts") cannot discriminate activity intensity for the activities of interest. This, in conjunction with variability in output from different systems and lack of commonality across manufacturers, limits the usefulness of commercial devices. This paper identifies anthropometric and kinematic sources of inter-athlete variability in accelerometer output, leading to an alternate energy expenditure estimator based mainly on step frequency modified by anthropometric measures. This energy expenditure estimator is more robust and not influenced by many sources of variability that affect the currently used estimator. In this system, low-power signal processing was implemented to extract both the energy estimator and other information of physiological and statistical interest     

Ultrastructure of the spermatozoa and eggs of the ocean pout (Macrozoarces americanus L.), an internally fertilizing marine fish

Ultrastructure of sperm and eggs of the ocean pout (Macrozoarces americanus L.), an internally fertilizing marine teleost, was examined by scanning and transmission electron microscopy. The results showed that the sperm do not have an acrosome but have a very long mid-piece (one to two times the sperm head length) containing numerous well-developed elongated mitochondria. The sperm also have two tails (is biflagellate) each consisting of nine peripheral and one central pair (9 +/- 2) of microtubules. This long mid-piece and the biflagellate nature of the sperm appear to be associated with the long life-span of the sperm and with sperm dispersal in the ovary to fertilize the eggs internally. The ocean pout eggs are enveloped by a porous chorionic membrane similar to that found in other teleosts but have two micropyles, a condition likely related to a mechanism of egg fertilization which increases the egg fertility in the presence of low sperm numbers. Following insemination, some biochemically undefined excretions appeared on the surface of fertilized eggs and led to the acquisition of adherent capability of the eggs which formed a tightly associated egg mass in sea water.