Logisztika 4.0 - Intelligens megoldások az elosztási logisztika optimalizálására – Intelligens elosztási logisztikai rendszerek : Logistics 4.0 – Intelligent designs in distribution logistics

Industry 4.0 and as a relation Logistics 4.0 is a popular and trending topic in these days – be it researches or business aspects for companies. As distribution logistics is also one of the most important and continuously optimized process of the market players there are significant advantages to be derived of using intelligent designs in it. To be able to make the right choices and decisions about utilizing these resources and optimizing the neccessary, expectable outcome it is inevitable to have the proper and comprehensive knowledge – whether it is a market leader who has the best knowledge and resources to use the relevant tools and technologies in their daily operation or a small player who has limited capabilities and only able to follow these. This gave me the reason to take a deep look into it. Kivonat Népszerű és sok lehetőséget rejtő téma napjainkban az Ipar 4.0 és az ehhez kapcsolódó Logisztika 4.0 – mind kutatási, mind hatékonyságnövelési szempontból a vállalatok részéről. Mivel az elosztási logisztika a legtöbb piaci szereplő számára egy kulcsfontosságú és folyamatosan optimalizált folyamat, jelentős előnyök származtathatók a releváns intelligens rendszerek alkalmazásából. Ahhoz, hogy egy vállalat – legyen szó piacvezető, fenti technológiákat alkalmazó vagy kisebb, éppen csak azokkal ismerkedő piaci szereplőről – megfelelő döntést tudjon hozni ezen lehetőségek kiaknázásáról elengedhetetlen azok ismerete, a befektetett erőforrások és a várható előnyök optimalizálása. Kulcsszavak: Ipar 4.0, elosztási logisztika, digitalizáció, intelligens logisztika. &nbsp

Targeting the interface of the pathological complex of α-synuclein and TPPP/p25

AbstractThe pathological interaction of intrinsically disordered proteins, such as α-synuclein (SYN) and Tubulin Polymerization Promoting Protein (TPPP/p25), is often associated with neurodegenerative disorders. These hallmark proteins are co-enriched and co-localized in brain inclusions of Parkinson's disease and other synucleinopathies; yet, their successful targeting does not provide adequate effect due to their multiple functions. Here we characterized the interactions of the human recombinant wild type SYN, its truncated forms (SYN1–120, SYN95–140), a synthetized peptide (SYN126–140) and a proteolytic fragment (SYN103–140) with TPPP/p25 to identify the SYN segment involved in the interaction. The binding of SYN103–140 to TPPP/p25 detected by ELISA suggested the involvement of a segment within the C-terminal of SYN. The studies performed with ELISA, Microscale Thermophoresis and affinity chromatography proved that SYN95–140 and SYN126–140 – in contrast to SYN1–120 – displayed significant binding to TPPP/p25. Fluorescence assay with ANS, a molten globule indicator, showed that SYN, but not SYN1–120 abolished the zinc-induced local folding of both the full length as well as the N- and C-terminal-free (core) TPPP/p25; SYN95–140 and SYN126–140 were effective as well. The aggregation-prone properties of the SYN species with full length or core TPPP/p25 visualized by immunofluorescent microscopy demonstrated that SYN95–140 and SYN126–140, but not SYN1–120, induced co-enrichment and massive intracellular aggregation after their premixing and uptake from the medium. These data with their innovative impact could contribute to the development of anti-Parkinson drugs with unique specificity by targeting the interface of the pathological TPPP/p25-SYN complex

Construction of a Xylanase A Variant Capable of Polymerization

The aim of our work is to furnish enzymes with polymerization ability by creating fusion constructs with the polymerizable protein, flagellin, the main component of bacterial flagellar filaments. The D3 domain of flagellin, exposed on the surface of flagellar filaments, is formed by the hypervariable central portion of the polypeptide chain. D3 is not essential for filament formation. The concept in this project is to replace the D3 domain with suitable monomeric enzymes without adversely affecting polymerization ability, and to assemble these chimeric flagellins into tubular nanostructures. To test the feasibility of this approach, xylanase A (XynA) from B. subtilis was chosen as a model enzyme for insertion into the central part of flagellin. With the help of genetic engineering, a fusion construct was created in which the D3 domain was replaced by XynA. The flagellin-XynA chimera exhibited catalytic activity as well as polymerization ability. These results demonstrate that polymerization ability can be introduced into various proteins, and building blocks for rationally designed assembly of filamentous nanostructures can be created

Zinc-induced structural changes of the disordered TPPP/p25 inhibits its degradation by the proteasome

AbstractTubulin Polymerization Promoting Protein/p25 (TPPP/p25), a neomorphic moonlighting protein displaying both physiological and pathological functions, plays a crucial role in the differentiation of the zinc-rich oligodendrocytes, the major constituent of myelin sheath; and it is enriched and co-localizes with α-synuclein in brain inclusions hallmarking Parkinson's disease and other synucleinopathies. In this work we showed that the binding of Zn2+ to TPPP/p25 promotes its dimerization resulting in increased tubulin polymerization promoting activity. We also demonstrated that the Zn2+ increases the intracellular TPPP/p25 level resulting in a more decorated microtubule network in CHO10 and CG-4 cells expressing TPPP/p25 ectopically and endogenously, respectively. This stabilization effect is crucial for the differentiation and aggresome formation under physiological and pathological conditions, respectively. The Zn2+-mediated effect was similar to that produced by treatment of the cells with MG132, a proteasome inhibitor or Zn2+ plus MG132 as quantified by cellular ELISA. The enhancing effect of zinc ion on the level of TPPP/p25 was independent of the expression level of the protein produced by doxycycline induction at different levels or inhibition of the protein synthesis by cycloheximide. Thus, we suggest that the zinc as a specific divalent cation could be involved in the fine-tuning of the physiological TPPP/p25 level counteracting both the enrichment and the lack of this protein leading to distinct central nervous system diseases

A Kapcsolati Elégedettség Skála magyar változatának (RAS-H) pszichometriai jellemzői

Elméleti háttér: A Hendrick (1988) által kidolgozott Kapcsolati Elégedettség Skálát (Relationship Assessment Scale, RAS) gyakran, változatos kutatási területeken alkalmazzák a párkapcsolati elégedettség mérésére. Cél: A tanulmányban bemutatjuk a kérdőív magyar változatát (RAS-H) és értékeljük annak pszichometriai jellemzőit. Módszer: Az elemzés 270 házas-, illetve együtt élő pár (átlagéletkor férfiaknál 39,8 ± 10,5, nőknél 37,6 ± 9,9 év) keresztmetszeti, kérdőíves adatfelvételén alapul. A részletes szociodemográfiai adatok és a RAS-H felvétele mellett a válaszadó párok kitöltötték az Élettel való Elégedettség Skálát (SWLS-H), a Rosenberg Önértékelés Skálát (RSES-H), az Élet Értelme Kérdőívet (MLQ-H) és mértük a szubjektív egészségi állapotot is. Eredmények: A mérőeszköz hét tétele a konfirmatív faktorelemzés alapján mindkét nemnél egy faktorba tartozik, az így képzett skála belső konzisztenciája (Cronbach-alfa férfiaknál = 0,843, nőknél = 0,897) és teszt—reteszt megbízhatósága (r = 0,90) kiváló. A kapcsolati elégedettség mértéke nagyrészt független volt a szociodemográfiai jellemzőktől, viszont mindkét nemnél pozitívan függött össze a szexuális elégedettséggel (r = 0,425 és 0,492), illetve a lelki egészség más mutatóival, így az élettel való elégedettséggel, az élet értelmességével és az önértékeléssel (r = 0,207 és 0,470 között), nőknél pedig az élettel való elégedettség többi jellemzőktől — így az élet értelmességétől és az önértékeléstől — független prediktorának is bizonyult (béta = 0,294). Következtetések: A RAS-H az elemzések alapján a párkapcsolati elégedettség megbízható és érvényes mérőeszköze. | Background: Relationship Assessment Scale (RAS, Hendrick, 1988) is a frequently applied measure for assessing relationship satisfaction in various research areas. Aim: In the present study, we present the Hungarian version of the RAS (RAS-H) and evaluate its psychometric characteristics. Method: Analyses were based on data from a cross-sectional questionnaire study of cohabiting and married couples (N = 270 couples; age: 39.8 ± 10.5 years for male and 37.6 ± 9.9 years for female respondents). Detailed sociodemographic data as well as relationship satisfaction were assessed together with life satisfaction (SWLS), meaning in life (MLQ), self-esteem (RSES), and self-rated health. Results: Confirmatory factor analysis revealed a unidmensional structure of the seven items of RAS-H for both sexes. Internal consistency (Cronbach’s alphas of 0.843 for men and 0.897 for women) and test—retest stability (r = 0.90) estimates were excellent. Level of relationship satisfaction was independent of most of the sociodemographic characteristics, but associated positively with sexual satisfaction (r = 0.425 and 0.492) as well as with life satisfaction, self-esteem, and meaning in life (rs between 0.207 and 0.470). Moreover, relationship satisfaction predicted life satisfaction positively (beta = 0.294) and independently from presence of meaning in life and self-esteem among females but not among males. Conclusions: The results indicate that the Hungarian version of the Relationship Assessment Scale (RAS-H) is a reliable and valid measure for assessing the satisfaction with intimate relationships

Trends in route planning with the tools of intelligent distribution logistics

The basic purpose of the article is to provide a sufficiently detailed and comprehensive overview about route planning concepts, logics, trends and opportunities for the relevant companies in the sector. Lack of resources or the strategic point of view or some other certain reasons are often obstruct the small and medium-sized companies to have a deep-dive validation of these factors - causing significant competitive disadvantages in terms of strategy and planning. If we do not see through properly the to-do tasks, possibly areas for development, managed by the operation we can significantly make harder decision-making process at any level. However, in the knowledge of all these, strategy of development or a possible system introduction – including methodology and required toold - can easily be determined

Challenging drug target for Parkinson's disease: pathological complex of the chameleon TPPP/p25 and alpha-synuclein proteins

The hallmarks of Parkinson's disease and other synucleinopathies, Tubulin Polymerization Promoting Protein (TPPP/p25) and α-synuclein (SYN) have two key features: they are disordered and co-enriched/co-localized in brain inclusions. These Neomorphic Moonlighting Proteins display both physiological and pathological functions due to their interactions with distinct partners. To achieve the elective targeting of the pathological TPPP/p25-SYN but not the physiological TPPP/p25-tubulin complex, their interfaces were identified as a specific innovative strategy for the development of anti-Parkinson drugs. Therefore, the interactions of TPPP/p25 with tubulin and SYN were characterized which suggested the involvements of the 178–187 aa and 147–156 aa segments in the complexation of TPPP/p25 with tubulin and SYN, respectively. However, various truncated and deletion mutants reduced but did not abolish the interactions except one mutant; in addition synthetized fragments corresponding to the potential binding segments of TPPP/p25 failed to interact with SYN. In fact, the studies of the multiple interactions at molecular and cellular levels revealed the high conformational plasticity, chameleon feature, of TPPP/p25 that ensures exceptional functional resilience; the lack of previously identified binding segments could be replaced by other segments. The experimental results are underlined by distinct bioinformatics tools. All these data revealed that although targeting chameleon proteins is a challenging task, nevertheless, the validation of a drug target can be achieved by identifying the interface of complexes of the partner proteins existing at the given pathological conditions

Modulation of microtubule acetylation by the interplay of TPPP/p25, SIRT2 and new anticancer agents with anti-SIRT2 potency

Abstract The microtubule network exerts multifarious functions controlled by its decoration with various proteins and post-translational modifications. The disordered microtubule associated Tubulin Polymerization Promoting Protein (TPPP/p25) and the NAD+-dependent tubulin deacetylase sirtuin-2 (SIRT2) play key roles in oligodendrocyte differentiation by acting as dominant factors in the organization of myelin proteome. Herein, we show that SIRT2 impedes the TPPP/p25-promoted microtubule assembly independently of NAD+; however, the TPPP/p25-assembled tubulin ultrastructures were resistant against SIRT2 activity. TPPP/p25 counteracts the SIRT2-derived tubulin deacetylation producing enhanced microtubule acetylation. The inhibition of the SIRT2 deacetylase activity by TPPP/p25 is evolved by the assembly of these tubulin binding proteins into a ternary complex, the concentration-dependent formation of which was quantified by experimental-based mathematical modelling. Co-localization of the SIRT2-TPPP/p25 complex on the microtubule network was visualized in HeLa cells by immunofluorescence microscopy using Bimolecular Fluorescence Complementation. We also revealed that a new potent SIRT2 inhibitor (MZ242) and its proteolysis targeting chimera (SH1) acting together with TPPP/p25 provoke microtubule hyperacetylation, which is coupled with process elongation only in the case of the degrader SH1. Both the structural and the functional effects manifesting themselves by this deacetylase proteome could lead to the fine-tuning of the regulation of microtubule dynamics and stability

Identification of motives mediating alternative functions of the neomorphic moonlighting TPPP/p25

The disordered Tubulin Polymerization Promoting Protein (TPPP/p25), a prototype of neomorphic moonlighting proteins, displays physiological and pathological functions by interacting with distinct partners. Here the role of the disordered N- and C-termini straddling a middle flexible segment in the distinct functions of TPPP/p25 was established, and the binding motives responsible for its heteroassociations with tubulin and α-synuclein, its physiological and pathological interacting partner, respectively, were identified. We showed that the truncation of the disordered termini altered the folding state of the middle segment and has functional consequences concerning its physiological function. Double truncation diminished its binding to tubulin/microtubules, consequently the tubulin polymerization/microtubule bundling activities of TPPP/p25 were lost highlighting the role of the disordered termini in its physiological function. In contrast, interaction of TPPP/p25 with α-synuclein was not affected by the truncations and its α-synuclein aggregation promoting activity was preserved, showing that the α-synuclein binding motif is localized within the middle segment. The distinct tubulin and α-synuclein binding motives of TPPP/p25 were also demonstrated at the cellular level: the double truncated TPPP/p25 did not align along the microtubules in contrast to the full length form, while it induced α-synuclein aggregation. The localization of the binding motives on TPPP/p25 were established by specific ELISA experiments performed with designed and synthesized peptides: motives at the 178-187 and 147-156 segments are involved in the binding of tubulin and α-synuclein, respectively. The dissimilarity of these binding motives responsible for the neomorphic moonlighting feature of TPPP/p25 has significant innovative impact in anti-Parkinson drug research