Nonlinear Model Predictive Control Of A Distillation Column Using Hammerstein Model And Nonlinear Autoregressive Model With Exogenous Input.

Turus penyulingan adalah unit proses penting dalam industri penapisan petroleum dan kimia. Ia perlu dikawal hampir dengan keadaan-keadaan pengendalian yang optima demi insentif- nsentif ekonomi. Distillation column is an important processing unit in petroleum refining and chemical industries, and needs to be controlled close to the optimum operating conditions because of economic incentives

Relationship Between Interpersonal Skills, Emotional Intelligence And Managerial Performance At Indah Water Konsortium Sdn Bhd.

Di era ini, para pengurus bertanggungjawab untuk mengenalpasti kekuatan mereka Every manager has that something special that makes them most effective as a manager of people and a leader in an industry

Environmental neurotoxin dieldrin induces apoptosis via caspase-3-dependent proteolytic activation of protein kinase C delta (PKCdelta): Implications for neurodegeneration in Parkinson's disease

BackgroundIn previous work, we investigated dieldrin cytotoxicity and signaling cell death mechanisms in dopaminergic PC12 cells. Dieldrin has been reported to be one of the environmental factors correlated with Parkinson's disease and may selectively destroy dopaminergic neurons.MethodsHere we further investigated dieldrin toxicity in a dopaminergic neuronal cell model of Parkinson's disease, namely N27 cells, using biochemical, immunochemical, and flow cytometric analyses.ResultsIn this study, dieldrin-treated N27 cells underwent a rapid and significant increase in reactive oxygen species followed by cytochrome c release into cytosol. The cytosolic cytochrome c activated caspase-dependent apoptotic pathway and the increased caspase-3 activity was observed following a 3 hr dieldrin exposure in a dose-dependent manner. Furthermore, dieldrin caused the caspase-dependent proteolytic cleavage of protein kinase C delta (PKCδ) into 41 kDa catalytic and 38 kDa regulatory subunits in N27 cells as well as in brain slices. PKCδ plays a critical role in executing the apoptotic process in dieldrin-treated dopaminergic neuronal cells because pretreatment with the PKCδ inhibitor rottlerin, or transfection and over-expression of catalytically inactive PKCδ(K)³⁷⁶(R), significantly attenuates dieldrin-induced DNA fragmentation and chromatin condensation.ConclusionTogether, we conclude that caspase-3-dependent proteolytic activation of PKCδ is a critical event in dieldrin-induced apoptotic cell death in dopaminergic neuronal cells

Protein kinase D1 (PKD1) activation mediates a compensatory protective response during early stages of oxidative stress-induced neuronal degeneration

<p>Abstract</p> <p>Background</p> <p>Oxidative stress is a key pathophysiological mechanism contributing to degenerative processes in many neurodegenerative diseases and therefore, unraveling molecular mechanisms underlying various stages of oxidative neuronal damage is critical to better understanding the diseases and developing new treatment modalities. We previously showed that protein kinase C delta (PKCδ) proteolytic activation during the late stages of oxidative stress is a key proapoptotic signaling mechanism that contributes to oxidative damage in Parkinson's disease (PD) models. The time course studies revealed that PKCδ activation precedes apoptotic cell death and that cells resisted early insults of oxidative damage, suggesting that some intrinsic compensatory response protects neurons from early oxidative insult. Therefore, the purpose of the present study was to characterize protective signaling pathways in dopaminergic neurons during early stages of oxidative stress.</p> <p>Results</p> <p>Herein, we identify that protein kinase D1 (PKD1) functions as a key anti-apoptotic kinase to protect neuronal cells against early stages of oxidative stress. Exposure of dopaminergic neuronal cells to H₂O₂or 6-OHDA induced PKD1 activation loop (PKD1S744/748) phosphorylation long before induction of neuronal cell death. Blockade of PKCδ cleavage, PKCδ knockdown or overexpression of a cleavage-resistant PKCδ mutant effectively attenuated PKD1 activation, indicating that PKCδ proteolytic activation regulates PKD1 phosphorylation. Furthermore, the PKCδ catalytic fragment, but not the regulatory fragment, increased PKD1 activation, confirming PKCδ activity modulates PKD1 activation. We also identified that phosphorylation of S916 at the C-terminal is a preceding event required for PKD1 activation loop phosphorylation. Importantly, negative modulation of PKD1 by the RNAi knockdown or overexpression of PKD1^S916Aphospho-defective mutants augmented oxidative stress-induced apoptosis, while positive modulation of PKD1 by the overexpression of full length PKD1 or constitutively active PKD1 plasmids attenuated oxidative stress-induced apoptosis, suggesting an anti-apoptotic role for PKD1 during oxidative neuronal injury.</p> <p>Conclusion</p> <p>Collectively, our results demonstrate that PKCδ-dependent activation of PKD1 represents a novel intrinsic protective response in counteracting early stage oxidative damage in neuronal cells. Our results suggest that positive modulation of the PKD1-mediated compensatory protective mechanism against oxidative damage in dopaminergic neurons may provide novel neuroprotective strategies for treatment of PD.</p

Acute hydrogen sulfide-induced neuropathology and neurological sequelae: challenges for translational neuroprotective research.

Hydrogen sulfide (H2 S), the gas with the odor of rotten eggs, was formally discovered in 1777, over 239 years ago. For many years, it was considered an environmental pollutant and a health concern only in occupational settings. Recently, however, it was discovered that H2 S is produced endogenously and plays critical physiological roles as a gasotransmitter. Although at low physiological concentrations it is physiologically beneficial, exposure to high concentrations of H2 S is known to cause brain damage, leading to neurodegeneration and long-term neurological sequelae or death. Neurological sequelae include motor, behavioral, and cognitive deficits, which are incapacitating. Currently, there are concerns about accidental or malicious acute mass civilian exposure to H2 S. There is a major unmet need for an ideal neuroprotective treatment, for use in the field, in the event of mass civilian exposure to high H2 S concentrations. This review focuses on the neuropathology of high acute H2 S exposure, knowledge gaps, and the challenges associated with development of effective neuroprotective therapy to counteract H2 S-induced neurodegeneration

Conductance through single biphenyl molecules: symmetric and asymmetric coupling to electrodes

The contacts and the chemical bonds formed between metallic electrodes and molecules determine to a large extent the conductive properties of single molecular junctions, which represent the smallest possible active elements in an electronic circuit. We therefore investigated in a comparative study, using the break junction technique (MCBJ), the conductive properties of [1,1'-biphenyl]-4,4'-dithiol (M1) and of 4'-mercapto-[1,1'-biphenyl]-4-carbonitrile (M2) between gold electrodes. As a function of electrode separation, characterized by the conductance close to 0 V, we found several plateaus of relative stability, with those close to 0.01G(0) being the most pronounced. The overall conductance of symmetric and asymmetric molecules were surprisingly similar, only the range of stability was smaller for M2. While M1 yielded symmetric I-V-curves, only small asymmetries were detected for M2. These are also reflected in the comparable values for coupling parameters using the single level resonance model. The high conductance for the asymmetric molecule is interpreted as a result of coherent coupling of electronic states through the whole molecule, so that the outcome cannot be predicted just by adding conductive properties of individual molecular groups

Fyn kinase regulates microglial neuroinflammatory responses in cell culture and animal models of parkinson’s disease

Sustained neuroinflammation mediated by resident microglia is recognized as a key pathophysiological contributor to many neurodegenerative diseases, including Parkinson’s disease (PD), but the key molecular signaling events regulating persistent microglial activation have yet to be clearly defined. In the present study, we examined the role of Fyn, a non-receptor tyrosine kinase, in microglial activation and neuroinflammatory mechanisms in cell culture and animal models of PD. The well-characterized inflammogens LPS and TNFɑ rapidly activated Fyn kinase in microglia. Immunocytochemical studies revealed that activated Fyn preferentially localized to the microglial plasma membrane periphery and the nucleus. Furthermore, activated Fyn phosphorylated PKCδ at tyrosine residue 311, contributing to an inflammogen-induced increase in its kinase activity. Notably, the Fyn-PKCδ signaling axis further activated the LPSand TNFɑ-induced MAP kinase phosphorylation and activation of the NFB pathway, implying that Fyn is a major upstream regulator of proinflammatory signaling. Functional studies in microglia isolated from wild-type (Fyn) and Fyn knock-out (Fyn) mice revealed that Fyn is required for proinflammatory responses, including cytokine release as well as iNOS activation. Interestingly, a prolonged inflammatory insult induced Fyn transcript and protein expression, indicating that Fyn is upregulated during chronic inflammatory conditions. Importantly, in vivo studies using MPTP, LPS, or 6-OHDA models revealed a greater attenuation of neuroinflammatory responses in Fyn and PKCδ mice compared with wild-type mice. Collectively, our data demonstrate that Fyn is a major upstream signaling mediator of microglial neuroinflammatory processes in PD

Effect of Tax Structure on Income Inequality in Sri Lanka

Growing income inequality is seen as one of the most important global concerns in this decade. Hence, the Sustainable Development Goals (SDGs) 2030 aims at reducing income inequality within and among countries. IMF emphasizes that income inequality emerged as one of the critical concerns for economic policy in both developed and developing countries. However, as shown by the UN, Sri Lanka is far lower than the South Asian regional income distribution standards owing to its high inequality. At the same time, tax revenue has become one of the major concerns in the country due to its broadened internal deficit. In this background, this study examines the short-run and long-run effects of tax structure on income inequality in Sri Lanka utilizing annual statistics from 1980 to 2019 by employing the ARDL model. Findings revealed that in the long run, value-added and excise taxes have a significant association with income inequality in Sri Lanka. However, the association between personal income tax and income inequality was positive but insignificant. In contrast, corporate income tax and import duty have a statistically significant negative association with income inequality in Sri Lanka. Further, in the short run, at the overall level taxes are not significantly associated with income inequality except the personal income tax which has a significant negative association with income inequality. &nbsp

Phytic Acid Protects against 6-Hydroxydopamine-Induced Dopaminergic Neuron Apoptosis in Normal and Iron Excess Conditions in a Cell Culture Model

Iron may play an important role in Parkinson's disease (PD) since it can induce oxidative stress-dependent neurodegeneration. The objective of this study was to determine whether the iron chelator, phytic acid (IP6) can protect against 6-hydroxydopamine- (6-OHDA-) induced apoptosis in immortalized rat mesencephalic dopaminergic cells under normal and iron-excess conditions. Caspase-3 activity was increased about 6-fold after 6-OHDA treatment (compared to control; P < .001) and 30 μmol/L IP6 pretreatment decreased it by 38% (P < .05). Similarly, a 63% protection (P < .001) against 6-OHDA induced DNA fragmentation was observed with IP6 pretreatment. Under iron-excess condition, a 6-fold increase in caspase-3 activity (P < .001) and a 42% increase in DNA fragmentation (P < .05) with 6-OHDA treatment were decreased by 41% (P < .01) and 27% (P < .05), respectively, with 30 μmol/L IP6. Together, our data suggest that IP6 protects against 6-OHDA-induced cell apoptosis in both normal and iron-excess conditions, and IP6 may offer neuroprotection in PD

EGCG Protects against 6-OHDA-Induced Neurotoxicity in a Cell Culture Model

Background. Parkinson’s disease (PD) is a progressive neurodegenerative disease that causes severe brain dopamine depletion. Disruption of iron metabolism may be involved in the PD progression. Objective. To test the protective effect of (−)-epigallocatechin-3-gallate (EGCG) against 6-hydroxydopamine- (6-OHDA-) induced neurotoxicity by regulating iron metabolism in N27 cells. Methods. Protection by EGCG in N27 cells was assessed by SYTOX green assay, MTT, and caspase-3 activity. Iron regulatory gene and protein expression were measured by RT-PCR and Western blotting. Intracellular iron uptake was measured using 55Fe. The EGCG protection was further tested in primary mesencephalic dopaminergic neurons by immunocytochemistry. Results. EGCG protected against 6-OHDA-induced cell toxicity. 6-OHDA treatment significantly () increased divalent metal transporter-1 (DMT1) and hepcidin and decreased ferroportin 1 (Fpn1) level, whereas pretreatment with EGCG counteracted the effects. The increased 55Fe (by 96%, ) cell uptake confirmed the iron burden by 6-OHDA and was reduced by EGCG by 27% (), supporting the DMT1 results. Pretreatment with EGCG and 6-OHDA significantly increased () TH+ cell count (~3-fold) and neurite length (~12-fold) compared to 6-OHDA alone in primary mesencephalic neurons. Conclusions. Pretreatment with EGCG protected against 6-OHDA-induced neurotoxicity by regulating genes and proteins involved in brain iron homeostasis, especially modulating hepcidin levels