Hybrid make-to-stock and make-to-order systems: a taxonomic review

Production planning and control (PPC) systems that employ aspects from both make-to-order (MTO) and make-to-stock (MTS) production control are known as hybrid MTS/MTO systems. While both MTO and MTS separately have been studied extensively, their combined use has received less attention. However, the literature on this topic is growing and this paper shows that the review performed in this paper is an important addition to the field. We categorise relevant literature according to a novel taxonomy and show that hybrid MTS/MTO production control can be used in different contexts. In addition, an overview of the modelling techniques and methods used in these papers is provided. Based on the reviewed literature, relevant research questions and directions for future research are identified. Finally, it is shown that hybrid MTS/MTO production control is prevalent in practice by discussing research with industrial applications. The paper contains an overview of research on hybrid MTS/MTO production control to be used as reference for researchers active in the field, and provides managerial insights and directions for future research on this topic.     

Tetrahydroindoles as Multipurpose Screening Compounds and Novel Sirtuin Inhibitors

Indoles are privileged structures in medicinal and bioorganic chemistry that are particularly well suited to serve as platforms for diversity. Among many other therapeutic areas, the indole scaffold has been used to design aromatic compounds useful to interfere with enzymes engaged in the regulation of substrate acylation status, such as sirtuins. However, the planarity of the indole ring is not necessarily optimal for all target enzymes, especially when functionalization with aromatic side chains is required. Replacement of flat scaffolds by nonplanar molecular cores dominated by sp³ hybridization is a common strategy to avoid the disadvantages associated with poor solubility and high promiscuity, while covering less-well-explored areas of chemical space. Thus, we synthesized fragment-like tetrahydroindoles suitable for fragment-based drug discovery as well as a well-characterized small library intended as multipurpose screening compounds. For proof of principle, these compounds were screened against sirtuins 1–3, enzymes known to be addressable by indoles. We found that 2,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-1H-indole-3-carboxamides are potent and selective SIRT2 inhibitors. Compound 16 t displayed an IC₅₀ value of 0.98 μm and could serve as exquisite starting point for hit-to-lead profiling.     

The Critical Role of Passive Permeability in Designing Successful Drugs

Passive permeability is a key property in drug disposition and delivery. It is critical for gastrointestinal absorption, brain penetration, renal reabsorption, defining clearance mechanisms and drug-drug interactions. Passive diffusion rate is translatable across tissues and animal species, while the extent of absorption is dependent on drug properties, as well as in vivo physiology/pathophysiology. Design principles have been developed to guide medicinal chemistry to enhance absorption, which combine the balance of aqueous solubility, permeability and the sometimes unfavorable compound characteristic demanded by the target. Permeability assays have been implemented that enable rapid development of structure-permeability relationships for absorption improvement. Future advances in assay development to reduce nonspecific binding and improve mass balance will enable more accurately measurement of passive permeability. Design principles that integrate potency, selectivity, passive permeability and other ADMET properties facilitate rapid advancement of successful drug candidates to patients.     

Color preferences for different topics in connection to personal characteristics

Studies on color preferences are dependent on the topic and the relationships with personal characteristics, particularly personality, but these are seldom studied in one population. Therefore a questionnaire was collected from 1095 Dutch people asking for color preferences about different topics and relating them to personal characteristics. Color preferences regarding different topics show different patterns and significant differences were found between gender, age, education and personality such as being technical, being emotional or being a team player. Also, different colors were mentioned when asked for colors that stimulate to be quiet, energetic, and able to focus or creative. Probably, due to unconsciousness of contexts, many people had no color preference, a result that in the literature seldom is mentioned. Blue was the overall favorite color; however, most males chose for blue (25%) while most females had no color preference (18%). Black was the overall favorite color for clothing, mainly chosen by females (40%), while males primarily chose blue (27%). For building interiors subjects preferred white. For moods, subjects preferred white for being quiet or being able to focus, red for being energetic and had no color preference for being creative. It is concluded that color preferences are dependent upon the topic, and personal characteristics. The findings are important for architects, interior designers, fashion designers and product designers to have a basic idea of preferred colors for different objects by different types of people. © 2013 Wiley Periodicals, Inc. Col Res Appl, 40, 62–71, 2015     

On the origin of strain hardening in glassy polymers

The influence of network density on the strain hardening behaviour of amorphous polymers is studied. The network density of polystyrene is altered by blending with poly(2,6-dimethyl-1,4-phenylene-oxide) and by cross-linking during polymerisation. The network density is derived from the rubber-plateau modulus determined by dynamic mechanical thermal analysis. Subsequently uniaxial compression tests are performed to obtain the intrinsic deformation behaviour and, in particular, the strain hardening modulus. At room temperature, the strain hardening modulus proves to be proportional to the network density, irrespective of the nature of the network, i.e. physical entanglements or chemical cross-links. With increasing temperature, the strain hardening modulus is observed to decrease. This decrease appears to be related to the influence of thermal mobility of the chains, determined by the distance to the glass-transition temperature (T−T_g).     

Calibrated Free-Space Microwave Measurements With an Ultrawideband Reflectometer-Antenna System

We present a 3-12 GHz compact mixer-based reflectometer (CMR) and horn antenna system, and demonstrate its use in detecting backscatter signals with a free space calibration procedure. We evaluate the frequency-domain performance of the CMR-antenna system for measuring the complex reflection coefficient of a dielectric slab and compare it with that of a commercial vector network analyzer (VNA)-antenna setup. Time-domain responses are also investigated, and show the effectiveness of this calibration method. This low-cost, compact system eliminates the need for traditional mechanical standards and a VNA, is effective in reducing reflection artifacts, and allows for flexibility in the placement of reference planes; thus it is well suited for array-based imaging applications     

Prediction of brittle-to-ductile transitions in polystyrene

In this study it is attempted to predict brittle-to-ductile transitions (BDTs) in polystyrene blends, induced either by an increase in temperature or by a decrease in inter-particle distance. A representative, two-dimensional volume element (RVE) of a polystyrene matrix with 20% circular voids, is deformed in tension. During deformation a hydrostatic-stress based craze-nucleation criterion [1] is evaluated. The simulations demonstrate that crazes initiate at low temperatures while a transition from crazing to shear yielding (BDT) is found around 75 °C. The numerical results correlate well with tensile tests on similar heterogeneous polystyrene. The presence of an absolute length, as experimentally found, is more difficult to explain. Near a free surface a T_g-depression is measured for polystyrene and also the resistance to indentation in polystyrene is lower than expected from bulk properties. Both observations are rationalised by an enhanced segmental mobility of chains near a free surface. As a consequence of these findings, an absolute length-scale could be incorporated in the numerical simulations. For simplicity, the length-scale is modelled by taking a temperature gradient over a thin layer near the internal free surfaces of the RVE. Deformation of the RVE with different absolute length-scales shows that indeed also the experimentally found brittle-to-ductile transition can be predicted if the ligament thickness between the inclusions (‘voids’) in polystyrene is below a critical value of ca. 15 nm.     

Sigma-delta modulators operating at a limit cycle

A new type of sigma-delta modulator that operates in a special mode named limit-cycle mode (LCM) is proposed. In this mode, most of the SDM building blocks operate at a frequency that is an integer fraction of the applied sampling frequency. That brings several very attractive advantages: a reduction of the required power consumption per converted bandwidth, an immunity to excessive loop delays and to digital-analog converter waveform asymmetry and a higher tolerance to clock imperfections. The LCMs are studied via a graphical application of the describing function theory. A second-order continuous time SDM with 5 MHz conversion bandwidth, 1 GHz sampling frequency and 125 MHz limit-cycle frequency is used as a test case for the evaluation of the performance of the proposed type of modulators. High level and transistor simulations are presented and compared with the traditional SDM designs.