Inhibition of Autophagy Does Not Re-Sensitize Acute Myeloid Leukemia Cells Resistant to Cytarabine

Elevated activation of the autophagy pathway is currently thought to be one of the survival mechanisms allowing therapy-resistant cancer cells to escape elimination, including for cytarabine (AraC)-resistant acute myeloid leukemia (AML) patients. Consequently, the use of autophagy inhibitors such as chloroquine (CQ) is being explored for the re-sensitization of AraC-resistant cells. In our study, no difference in the activity of the autophagy pathway was detected when comparing AraC-Res AML cell lines to parental AraC-sensitive AML cell lines. Furthermore, treatment with autophagy inhibitors CQ, 3-Methyladenine (3-MA), and bafilomycin A1 (BafA1) did not re-sensitize AraC-Res AML cell lines to AraC treatment. However, in parental AraC-sensitive AML cells, treatment with AraC did activate autophagy and, correspondingly, combination of AraC with autophagy inhibitors strongly reduced cell viability. Notably, the combination of these drugs also yielded the highest level of cell death in a panel of patient-derived AML samples even though not being additive. Furthermore, there was no difference in the cytotoxic effect of autophagy inhibition during AraC treatment in matched de novo and relapse samples with differential sensitivity to AraC. Thus, inhibition of autophagy may improve AraC efficacy in AML patients, but does not seem warranted for the treatment of AML patients that have relapsed with AraC-resistant disease.     

Distributed ledger technology in supply chains: a transaction cost perspective

With the emergence of distributed ledger technology (DLT), numerous practitioners and researchers have proclaimed its beneficial impact on supply chain transactions in the future. However, the vast majority of DLT initiatives are discontinued after a short period. With the full potential of DLT laying far down the road, especially managers in supply chain management (SCM) seek for short-term cost-saving effects of DLT in order to achieve long-term benefits of DLT in the future. However, the extant research has bypassed grounding long-term as well as short-term effects of DLT on supply chain transaction with empirical data. We address this shortcoming, following an abductive research approach and combining empirical data from a multiple case study design with the corresponding literature. Our study reveals that the effects of DLT on supply chain transactions are two-sided. We found six effects of DLT solutions that have a cost-reducing or cost avoidance impact on supply chain transactions. In addition, we found two effects that change the power distribution between buyers and suppliers in transactions and a single effect that reduces the dependency of supply chain transactions on third parties. While cost-reducing and avoidance as well as dependency-reducing effects are positive effects, the change in power distribution might come with disadvantages. With these findings, the paper provides the first empirical evidence of the impact of DLT on supply chain transactions, which will enable managers to improve their assessment of DLT usage in supply chains.     

Effects of breed and age at slaughter on degradation of muscle lipids during processing of dry‐cured hams

Hams from Landrace, Duroc and Hampshire pigs slaughtered at ages 6, 7.5 and 9 months were processed to generate Norwegian Parma‐style hams. Lipid contents and the compositions of fatty acid classes (ΣSFA, ΣMUFA, ΣPUFA) within neutral lipids, phospholipids and free fatty acids were determined. Small differences in lipid degradation and composition of the classes were revealed. However, significant sensory differences related to lipids were observed. Breed was more important than age. Dry‐cured Hampshire hams gave a more intense mature odour that may be associated with higher overall lipid degradation. Unexpectedly, these hams also demonstrated high juiciness and tenderness, which could be related to the melting characteristics of the fat. Dry‐cured Duroc hams showed a higher susceptibility towards rancidity, presumably associated with preferential oxidation of n‐6 fatty acids relative to C18:1 n‐9. Dry‐cured Landrace hams showed the lowest juiciness and tenderness, likely due to their lower fat content (marbling).     

The Role of Test Protocols in Automated Test Generation for Embedded-Core-Based System ICs

Modular testing is an attractive approach to testing large system ICs, especially if they are built from pre-designed reusable embedded cores. This paper describes an automated modular test development approach. The basis of this approach is that a core or module test is dissected into a test protocol and a test pattern list. A test protocol describes in detail how to apply one test pattern to the core, while abstracting from the specific test pattern stimulus and response values. Subsequent automation tasks, such as the expansion from core-level tests to system-chip-level tests and test scheduling, all work on test protocols, thereby greatly reducing the amount of compute time and data involved. Finally, an SOC-level test is assembled from the expanded and scheduled test protocols and the (so far untouched) test patterns. This paper describes and formalizes the notion of test protocols and the algorithms for test protocol expansion and scheduling. A running example is featured throughout the paper. We also elaborate on the industrial usage of the concepts described.     

RanGen: A Random Network Generator for Activity-on-the-Node Networks

In this paper, we describe RanGen, a random network generator for generating activity-on-the-node networks and accompanying data for different classes of project scheduling problems. The objective is to construct random networks which satisfy preset values of the parameters used to control the hardness of a problem instance. Both parameters which are related to the network topology and resource-related parameters are implemented. The network generator meets the shortcomings of former network generators since it employs a wide range of different parameters which have been shown to serve as possible predictors of the hardness of different project scheduling problems. Some of them have been implemented in former network generators while others have not.     

Polyimide foams from powder: Experimental analysis of competitive diffusion phenomena

In the present study, various diffusive processes have been investigated during foaming of powdered precursors of polyimide. A detailed analysis of the powdered precursor's characteristics allows for an enhanced morphological understanding of the resulting microstructures and foam unit cell. Parameters that are central to the foaming process such as particle morphology, volatile concentration and sorption-desorption processes are evaluated. Isothermal and non-isothermal desorption experiments have been carried out by thermogravimetric analysis (TGA), and specific diffusive processes have been correlated to thermodynamic and kinetic transitions by means of modulated differential scanning calorimetry (MDSC) of the corresponding materials. It was found that two primary fluxes of volatiles, one out of the external surface of the particles (responsible for volatile desorption) and the other into the growing bubble (responsible for vapor supersaturation inside the bubble) compete against each other creating a competitive scenario that becomes the controlling factor for potential inflation within the precursor particles.     

Tribotronics—Towards active tribology

A constant trend towards more compact mechanical systems with higher power densities and increased thermo-mechanical loads emphasises the importance of the development of new design approaches and novel tribological systems. Ignoring this may cause a significant slow down in technological and industrial development. Tribotronics or active tribology based on adaptive performance is thought of as being critical in the implementation of smart machine concepts. Recognition of the importance of tribotronics, or active control of system loss outputs, such as those through friction and wear will have significant beneficial economic consequences as a result of the associated accelerated rate of technological progress. These smart tribotronic systems can be embedded in a great variety of machines and mechanisms. If this integration is made at the design stage, products that are more flexible, efficient and reliable can be produced. The concept of tribotronics is presented and discussed in this paper. Some illustrative examples that show the feasibility of an “active” approach are given. In addition, various possibilities already reported in literature are discussed.     

Changing our view on design evaluation meetings methodology: a study of software technical review meetings

By contrast to design meetings, design evaluation meetings (DEMs) have generally been considered as situations in which, according to DEM methodologies, design activities are quite marginal. In a study of DEMs in software development, i.e. in technical review meetings following a particular review methodology, we showed: (i) the occurrence of design activities as part of an argumentation process; (ii) the relative importance of cognitive synchronisation as a prerequisite for evaluation; (iii) the important role played in evaluation by argumentation that makes explicit the underlying design rationale (DR). On the basis of our results, we discuss the potential for using DR methodologies in this kind of meetings.     

Deactivation of V2O5-WO3-TiO2 SCR catalyst at a biomass-fired combined heat and power plant

The deactivation of a commercial type V₂O₅-WO₃-TiO₂ monolith catalyst under biomass combustion was studied at a full-scale grate-fired power plant burning straw/wood using a slip stream pilot scale reactor. The aerosols in the flue gas consisted of a mixture of potassium chloride and sulphate. Three catalyst elements were exposed at 350 °C, and one element was exposed at 250 °C for comparison. The catalyst activity was measured in the reactor at the exposure temperature by addition of NH₃ and extra NO. The activity, in terms of a first-order rate constant, dropped by 52% after about 1140 h indicating a very fast deactivation compared to coal firing. It was also found that the reactor temperature was not of importance for the deactivation rate. SEM-EDX analysis showed that particle deposition and pore blocking contributed to the deactivation by decreasing the diffusion rate of NO and NH₃ into the catalyst. However, potassium also penetrated into the catalyst wall and the resulting average K/V ratio in the catalyst structure was high enough (about 0.3–0.5) for a significant chemical deactivation. Chemisorption studies carried out in situ showed that the amount of chemisorbed NH₃ on the catalyst decreased as a function of exposure time, which reveals that Brøndsted acid sites had reacted with potassium compounds and thereby rendered inactive. When washed by 0.5 M H₂SO₄ the regenerated catalyst regains a higher activity than that of the fresh catalyst at temperatures higher than 300 °C, but even though reactivation is possible, the deactivation rate appears too high for practical use of the SCR process in straw combustion.