88 research outputs found
Using triple-loop learning to identify adaptive behaviour of resilient supply chain
The contemporary environment of supply chains is characterized by discontinuity, being the source of unpredictable changes producing effects that are difficult to determine. Underestimating and not including the discontinuity in the managerial concept makes the supply chain homomorphic with respect to reality, thus, it is reflected only approximately (Jędralska, 1992). In other words, the situation of discontinuity is caused by the unreliability of the current management model. The answer to the discontinuity may be the formation of resilient supply chains that are aimed at developing specific patterns of adaptive behaviour. The aim of the article is to recognize the adaptive behaviours of a resilient supply chain in light of the assumptions of triple-loop learning in an organization. In the first part of the paper, the issue of a resilient supply chain is discussed, highlighting its adaptive capability. Next, the mechanism of preadaptation – adaptation of the supply chain based on triple-loop learning is explained. The final part of the paper presents the basic components of a resilient supply chain determining the adaptive behaviour consistent with triple-loop learning
The Effect of Sales Planning Practices on Manufacturing Strategy. An International Comparative Study.
Proper competitive strategy is the means of survival and development for manufacturing companies. In this vein, the producers should perceive a manufacturing strategy as the issue of crucial importance for their market position. It describes the use of manufacturing as a competitive weapon, as opposed to a function that is passive with respect to its competitive environment. Manufacturing companies differ in the way they meet the demand for their products. Some deliver products to their clients from finished goods inventories as their production anticipates customers' orders; others, however, manufacture only in response to customers' orders. In this connection the emphasis of manufacturing strategies is now more to competition in terms of time and customization. Time competition requires an emphasis on time which should not be wasted and is supported by fewer and faster activities being performed. On the other hand, customization means performing some activities according to the unique requirements of an individual customer.
Competition in terms of time and customization is reflected in one of the most popular classification of manufacturing strategy, namely: make-to-stock (MTO), assembly-to-order (ATO), make-to-order (MTO) and engineer-to-order (ETO). The application of the strategy may determine the extent the producers use forecasting techniques, combine environmental and market data into forecasting process and prepare forecasts for specific purposes. The goal of the paper is to make a cross-national comparison of the effect of forecasting practices on different types of manufacturing strategies applied in 343 producers from Europe, Asia and Africa. In order to achieve an empirical aim a necessary methodology and statistical analyses have been employed. In the result of the analysis multiple regression models have been developed for specific manufacturing strategies of producers from different countries worldwide. It enabled to make cross-national comparisons of the contribution to variance in manufacturing strategy
Air-stable and eco-friendly symmetrical imine with thiadiazole moieties in neutral and protonated form for perovskite photovoltaics
This paper proposes molecular and supramolecular concepts for potential application in perovskite solar cells. New air-stable symmetrical imine, with thiadiazole moieties PPL2: (5E,6E)-N2,N5-bis(4-(diphenylamino)benzylidene)-1,3,4-thiadiazole-2,5-diamine), as a hole-transporting material was synthesised in a single-step reaction, starting with commercially available and relatively inexpensive reagents, resulting in a reduction in the cost of the final product compared to Spiro-OMeTAD. Moreover, camphorsulfonic acid (CSA) in both enantiomeric forms was used to change the HOMO-LUMO levels and electric properties of the investigated imine-forming complexes. Electric, optical, thermal, and structural studies of the imine and its complexes with CSA were carried out to characterise the new material. Imine and imine/CSA complexes were also characterised in depth by the proton Nuclear Magnetic Resonance H NMR method. The position of nitrogen in the thidiazole ring influences the basicity of donor centres, which results in protonation in the imine bond. Simple devices of ITO/imine (with or without CSA(−) or CSA(+))/Ag/ITO architecture were constructed, and a thermographic camera was used to find the defects in the created devices. Electric behaviour was also studied to demonstrate conductivity properties under the forward current. Finally, the electrical properties of imine and its protonated form with CSA were compared with Spiro-OMeTAD. In general, the analysis of thermal images showed a very similar response of the samples to the applied potential in terms of the homogeneity of the formed organic layer. The TGA analysis showed that the investigated imine exhibits good thermal stability in air and argon atmospheres
Effect of SSR504734, a selective glycine transporter type 1 inhibitor, on seizure thresholds, neurotransmitter levels, and inflammatory markers in mice
Studies have revealed that inhibition of glycine
transporter type 1 (GlyT1) may provide a balanced regulation
between excitation and inhibition in some brain structures and,
thereby, modulate seizure activity. Data on the role of GlyT1 in
epilepsy are, however, very limited. Here, we examined the effect of
SSR504734, a highly selective and reversible GlyT1 inhibitor, on
three acute seizure tests in mice. We also evaluated its impact on
neurotransmitter levels in the relevant brain structures following
seizures, possible adverse effects, and changes in the levels of
inflammatory mediators in the serum and liver. In addition, in vivo
pharmacokinetic profile and in vitro ADME-Tox properties of SSR504734 were investigated. The results show that SSR504734
significantly increased the threshold for tonic hindlimb extension in the MEST test after acute and repeated treatment but had no
influence on seizure thresholds in the 6 Hz and i.v. PTZ seizure tests. SSR504734 did not affect the levels of glutamate, GABA,
glycine, or adenosine in brain structures of mice with MES-induced seizures. However, after acute treatment, the concentration of
glutamate and adenosine in the brainstem of control animals (i.e., without seizures) decreased. Moreover, SSR504734 increased the
levels of inflammatory markers (TNF-α, Il-1β, IL-6, IL-10, and TLR4) in serum. In vivo pharmacokinetic profiling and in vitro
ADME-Tox data confirmed suitable drug-like properties of SSR504734, including its notable penetration into brain tissue. However,
possible hepatotoxicity at higher doses should be taken into account. Further studies should be considered to better characterize the
SSR504734-mediated effects as well as to validate GlyT1 as a potential new molecular target in epilepsy treatment
Comparative assessment of the new PDE7 inhibitor - GRMS-55 and lisofylline in animal models of immune-related disorders : a PK/PD modeling approach
A novel, pan-PDE inhibitor exerts anti-fibrotic effects in human lung fibroblasts via inhibition of TGF- signaling and activation of cAMP/PKA signaling
Phosphodiesterase (PDE) inhibitors are currently a widespread and extensively studied group of anti-inflammatory and anti-fibrotic compounds which may find use in the treatment of numerous lung diseases, including asthma and chronic obstructive pulmonary disease. Several PDE inhibitors are currently in clinical development, and some of them, e.g., roflumilast, are already recommended for clinical use. Due to numerous reports indicating that elevated intracellular cAMP levels may contribute to the alleviation of inflammation and airway fibrosis, new and effective PDE inhibitors are constantly being sought. Recently, a group of 7,8-disubstituted purine-2,6-dione derivatives, representing a novel and prominent pan-PDE inhibitors has been synthesized. Some of them were reported to modulate transient receptor potential ankyrin 1 (TRPA1) ion channels as well. In this study, we investigated the effect of selected derivatives (832-a pan-PDE inhibitor, 869-a TRPA1 modulator, and 145-a pan-PDE inhibitor and a weak TRPA1 modulator) on cellular responses related to airway remodeling using MRC-5 human lung fibroblasts. Compound 145 exerted the most considerable effect in limiting fibroblast to myofibroblasts transition (FMT) as well as proliferation, migration, and contraction. The effect of this compound appeared to depend mainly on its strong PDE inhibitory properties, and not on its effects on TRPA1 modulation. The strong anti-remodeling effects of 145 required activation of the cAMP/protein kinase A (PKA)/cAMP response element-binding protein (CREB) pathway leading to inhibition of transforming growth factor type β1 (TGF-β1) and Smad-dependent signaling in MRC-5 cells. These data suggest that the TGF-β pathway is a major target for PDE inhibitors leading to inhibitory effects on cell responses involved in airway remodeling. These potent, pan-PDE inhibitors from the group of 7,8-disubstituted purine-2,6-dione derivatives, thus represent promising anti-remodeling drug candidates for further research
Synthesis and in vitro evaluation of anti-inflammatory, antioxidant, and anti-fibrotic effects of new 8-aminopurine-2,6-dione-based phosphodiesterase inhibitors as promising anti-asthmatic agents
Phosphodiesterase (PDE) inhibitors are currently an extensively studied group of compounds that can bring many benefits in the treatment of various inflammatory and fibrotic diseases, including asthma. Herein, we describe a series of novel N’-phenyl- or N’-benzylbutanamide and N’-arylidenebutanehydrazide derivatives of 8-aminopurine-2,6-dione (27–43) and characterized them as prominent pan-PDE inhibitors. Most of the compounds exhibited antioxidant and anti-inflammatory activity in lipopolysaccharide (LPS)-induced murine macrophages RAW264.7. The most active compounds (32–35 and 38) were evaluated in human bronchial epithelial cells (HBECs) derived from asthmatics. To better map the bronchial microenvironment in asthma, HBECs after exposure to selected 8-aminopurine-2,6-dione derivatives were incubated in the presence of two proinflammatory and/or profibrotic factors: transforming growth factor type β (TGF-β) and interleukin 13 (IL-13). Compounds 32–35 and 38 significantly reduced both IL-13- and TGF-β-induced expression of proinflammatory and profibrotic mediators, respectively. Detailed analysis of their inhibition preferences for selected PDEs showed high affinity for isoenzymes important in the pathogenesis of asthma, including PDE1, PDE3, PDE4, PDE7, and PDE8. The presented data confirm that structural modifications within the 7 and 8 positions of the purine-2,6-dione core result in obtaining preferable pan-PDE inhibitors which in turn exert an excellent anti-inflammatory and anti-fibrotic effect in the bronchial epithelial cells derived from asthmatic patients. This dual-acting pan-PDE inhibitors constitute interesting and promising lead structures for further anti-asthmatic agent discovery
Selected electrochemical properties of 4,4’-((1E,1’E)-((1,2,4-Thiadiazole-3,5-diyl)bis(azaneylylidene))bis(methaneylylidene))bis(N,N-di-p-tolylaniline) towards perovskite solar cells with 14.4% efficiency
Planar perovskite solar cells were fabricated on F-doped SnO2 (FTO) coated glass substrates, with 4,4’-((1E,1’E)-((1,2,4-thiadiazole-3,5-diyl)bis(azaneylylidene))bis(methaneylylidene))bis(N,N-di-p-tolylaniline) (bTAThDaz) as hole transport material. This imine was synthesized in one step reaction, starting from commercially available and relatively inexpensive reagents. Electrochemical, optical, electrical, thermal and structural studies including thermal images and current-voltage measurements of the full solar cell devices characterize the imine in details. HOMO-LUMO of bTAThDaz were investigated by cyclic voltammetry (CV) and energy-resolved electrochemical impedance spectroscopy (ER-EIS) and were found at −5.19 eV and −2.52 eV (CV) and at −5.5 eV and −2.3 eV (ER-EIS). The imine exhibited 5% weight loss at 156 °C. The electrical behavior and photovoltaic performance of the perovskite solar cell was examined for FTO/TiO2/perovskite/bTAThDaz/Ag device architecture. Constructed devices exhibited good time and air stability together with quite small effect of hysteresis. The observed solar conversion efficiency was 14.4%
PK/PD studies on non-selective PDE inhibitors in rats using cAMP as a marker of pharmacological response
Using triple-loop learning to identify adaptive behaviour of resilient supply chain
The contemporary environment of supply chains is characterized by discontinuity, being the source of unpredictable changes producing effects that are difficult to determine. Underestimating and not including the discontinuity in the managerial concept makes the supply chain homomorphic with respect to reality, thus, it is reflected only approximately (Jędralska, 1992). In other words, the situation of discontinuity is caused by the unreliability of the current management model. The answer to the discontinuity may be the formation of resilient supply chains that are aimed at developing specific patterns of adaptive behaviour. The aim of the article is to recognize the adaptive behaviours of a resilient supply chain in light of the assumptions of triple-loop learning in an organization. In the first part of the paper, the issue of a resilient supply chain is discussed, highlighting its adaptive capability. Next, the mechanism of preadaptation – adaptation of the supply chain based on triple-loop learning is explained. The final part of the paper presents the basic components of a resilient supply chain determining the adaptive behaviour consistent with triple-loop learning.</jats:p
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