25 research outputs found

    Tensions in the periphery: Dependence and the trajectory of a low-cost productive model in the Central and Eastern European automotive industry

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    This article analyses the productive strategy adopted by Renault for its Dacia plant in Romania. It proposes a detailed analysis of the conditions for the success of the Logan project – Renault’s radical approach to the concept of the low-cost automobile. We look into both market- and production-related aspects that have made the Logan work and highlight the tensions sparked by Renault’s drive to capitalize on its favourable market situation as well as the success achieved by Dacia’s workers in defending their interests. In particular, we emphasize the company governance compromises that have shaped industrial relations at Dacia over the past decades and show how in recent years the maintaining of such a compromise has come increasingly into question due to threats by automation and relocation in a context of constantly rising wages and improving working conditions. Finally, we discuss the strategic dilemmas facing both management and labour and their possible resolutions, as well as the relevance of the Dacia case for understanding the future of Central and Eastern Europe as a peripheral region attracting automotive foreign direct investments

    Reactions of Cre with Methylphosphonate DNA: Similarities and Contrasts with Flp and Vaccinia Topoisomerase

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    Chien-Hui Ma is with UT Austin, Aashiq H. Kachroo is with UT Austin, Anna Macieszak is with Polish Academy of Sciences, Tzu-Yang Chen is with UT Austin, Piotr Guga is with Polish Academy of Sciences, Makkuni Jayaram is with UT Austin.Background -- Reactions of vaccinia topoisomerase and the tyrosine site-specific recombinase Flp with methylphosphonate (MeP) substituted DNA substrates, have provided important insights into the electrostatic features of the strand cleavage and strand joining steps catalyzed by them. A conserved arginine residue in the catalytic pentad, Arg-223 in topoisomerase and Arg-308 in Flp, is not essential for stabilizing the MeP transition state. Topoisomerase or its R223A variant promotes cleavage of the MeP bond by the active site nucleophile Tyr-274, followed by the rapid hydrolysis of the MeP-tyrosyl intermediate. Flp(R308A), but not wild type Flp, mediates direct hydrolysis of the activated MeP bond. These findings are consistent with a potential role for phosphate electrostatics and active site electrostatics in protecting DNA relaxation and site-specific recombination, respectively, against abortive hydrolysis. Methodology/Principal Findings -- We have examined the effects of DNA containing MeP substitution in the Flp related Cre recombination system. Neutralizing the negative charge at the scissile position does not render the tyrosyl intermediate formed by Cre susceptible to rapid hydrolysis. Furthermore, combining the active site R292A mutation in Cre (equivalent to the R223A and R308A mutations in topoisomerase and Flp, respectively) with MeP substitution does not lead to direct hydrolysis of the scissile MeP bond in DNA. Whereas Cre follows the topoisomerase paradigm during the strand cleavage step, it follows the Flp paradigm during the strand joining step. Conclusions/Significance -- Collectively, the Cre, Flp and topoisomerase results highlight the contribution of conserved electrostatic complementarity between substrate and active site towards transition state stabilization during site-specific recombination and DNA relaxation. They have potential implications for how transesterification reactions in nucleic acids are protected against undesirable abortive side reactions. Such protective mechanisms are significant, given the very real threat of hydrolytic genome damage or disruption of RNA processing due to the cellular abundance and nucleophilicity of water.This work was supported by the NIH award GM035654 to M. J. Partial support was provided by the Robert F. Welch Foundation (F-1274) and a Faculty Research Award from the University of Texas at Austin. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Microbiolog

    Evaluation and motivation of human resources

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    Why do we need motivated employees? The answer is survival. Motivated employees are needed in our rapidly changing workplaces. Motivated employees help organizations survive. Motivated employees are more productive. To be effective, managers need to understand what motivates employees within the context of the roles they perform

    Breakeven calculation of the company when starting a business

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    Starting a business involves planning, making key financial decisions, completing a series of legal activities, hiring reliable employees and after all of this, the success of the new firm is determined by a few steps, which every manager must take into account. One of these steps is adopting a company name, the calling card of the business, taking into consideration the related tips regarding its selection. When talking about a company, its mission must be clear and easy to understand. Thus, the description of the main activity and the general environment must be also present in the business plan

    Research on Investment Estimation when Deciding to Start a new Business.

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    An entrepreneur has to follow several steps when deciding to start a new business. Starting a business involves planning, making key financial decisions, completing a series of legal activities, hiring reliable employees and after all of this the success of the new firm is determined by a few steps, which every manager must take into account. One of these steps is adopting a company name, the calling card of the business, taking into consideration the related tips regarding its selection. Entrepreneur must estimate the initial investment and the necessary financial resources. When talking about a company its mission must be clear and easy to understand. Thus, the description of the main activity and the general environment must be present in the business plan as well

    Binding of phosphorothioate oligodeoxynucleotides to basic fibroblast growth factor, recombinant soluble CD4, laminin and fibronectin is P-chirality independent.

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    Antisense oligodeoxynucleotides can selectively inhibit the expression of individual genes and thus have potential applications in anticancer and antiviral therapy. A critical prerequisite to their use as therapeutic agents is the understanding of their non-specific interactions with biological structures, e.g. proteins. In this study we examined the interactions of P-chiral phosphorothioate oligodeoxynucleotides with several proteins. The Rp- and Sp- diastereomers, and racemic machine-made mixtures, or M-oligodeoxynucleotides were used independently as competitors of the binding of a probe, phosphodiester oligodeoxynucleotide bearing a 5' alkylating moiety, to rsCD4, bFGF and laminin. These oligodeoxynucleotides were also used as competitors of the binding of a non-alkylating probe M-phosphorothioate oligodeoxynucleotide, 5'-32P-SdT18 to fibronectin. The average values of and quantitative estimates for the IC50 of competition and the constant of competition (Kc) of Rp-, Sp- and M-stereoisomers of several homo- and heteropolymer oligodeoxynucleotides were determined and compared. Surprisingly, in the proteins we studied, the values of IC50 and Kc for the Rp-, Sp- and M-oligodeoxynucleotides were essentially identical. Thus, the ability of the phosphorothioate oligodeoxynucleotides we employed, to bind to the proteins studied in this work, is virtually independent of P-chirality. Our results also imply that the role of the purine and pyrimidine bases in oligodeoxynucleotide-protein interactions, as well as the nature of the contact points (sulfur versus oxygen) between the oligomer and the protein, may be relatively unimportant

    Dynamic NMR Structures of [Rp]- and [Sp]-Phosphorothioated DNA-RNA Hybrids: Is Flexibility Required for RNase H Recognition?

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    Chemically modified DNA oligonucleotides have been crucial to the development of antisense therapeutics. High-resolution structural studies of pharmaceutically relevant derivatives have been limited to only a few molecules. We have used NMR to elucidate the structure in solution of two DNA-RNA hybrids with the sequence d(CCTATAATCC)·r(GGAUUAUAGG). The two hybrids contain an unmodified RNA target strand, whereas the DNA strand contains one of two different stereoregular sugar-phosphate backbone linkages at each nucleotide: 1), [Rp]-phosphorothioate or 2), [Sp]-phosphorothioate. Homonuclear two-dimensional spectroscopy afforded nearly complete nonlabile proton assignments. Distance bounds, calculated from the nuclear Overhauser effect (NOE) crosspeak intensities via a complete relaxation matrix approach with the program MARDIGRAS, were used to restrain the structure of the two hybrids during simulations of molecular dynamics. Analysis of restrained molecular dynamics trajectories suggests that both hybrids are flexible, requiring the use of molecular dynamics with time-averaged restraints (MDtar) to generate ensembles of structures capable of satisfying the NMR data. In particular, the deoxyribose sugars of the DNA strand show strong evidence of repuckering. Furthermore, deoxyribose sugar repuckering is accompanied by increased flexibility of overall helical geometry. These observations, together with the analysis of the crystal structure of a hybrid duplex in complex with ribonuclease H (RNase H), suggested that this flexibility may be required for recognition by RNase H

    Effectiveness of Quadruple Fortified Salt Compared to Double and Single Fortified Salts in Improving Haemoglobin Levels Among Moderately Anemic Women Aged 18–49 Years in Rural Low Resource Setting: Randomized Clinical Trial

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    Paschal Mdoe,1 Venkatesh Mannar,2 Museveni Justine,1 Godfrey Guga,1 Rose Gadiye,1 Vincent Assey,3 Caroline Kimathi,1 Fatma Abdallah,3 John Paschal,1 Estomih Mduma,1 Levente Diosady2 1Department of Obstetrics and Gynecology, Haydom Lutheran Hospital, Manyara, Tanzania; 2Department of Food Engineering, University of Toronto, Toronto, ON, Canada; 3Department of Food and Nutrition, Tanzania Food and Nutrition Center, Dar Es Salaam, TanzaniaCorrespondence: Paschal Mdoe, P.O. Box 9000, Manyara, Tanzania, Tel +255754429346, Email [email protected]: Micronutrients (iron, iodine, vitamin B12 and folate) deficiency is prevalent globally affecting more than two billion people majority being from low- and middle-income countries. Women of reproductive age are in an increased risk of iron deficiency. About 29.4% of women aged 15– 49 years worldwide are estimated to be affected by iron deficiency. Food fortification with micronutrients is important in addressing micronutrients deficiency.Aim: To evaluate if the quadruple fortified with iodine, iron, vitamin B12, and folic acid (QFS), will be more effective in improving the hemoglobin level of women aged 18 to 49 years compared to the double fortified with iodine and iron (DFS) and iodized salt in rural Tanzania.Methods: A double-blinded three-arm randomized controlled trial was conducted between July 2020 and December 2021 at the Haydom Lutheran Hospital catchment area. We randomized women aged 18– 49 years with haemoglobin between 8 and 12 g/dl who were neither pregnant nor lactating into three groups 55 Iodized salts (IS), 57 Double fortified salt (DFS), and 57 quadruple fortified salt (QFS). The participants used study salt for 10 months.Results: Over the ten months of use of study salts, the overall mean haemoglobin level of women was significantly higher in QFS by 0.43g/dl compared to IS. The ferritin levels were significantly higher in QFS and DFS by 9.60ng/mL and 9.09ng/mL, respectively, compared to IS. Vitamin B12 was insignificantly higher in QFS by 52.19pg/mL compared to DFS, and folate concentration were insignificantly higher in QFS by 7.57nmoL/L and 4.51nmoL/L compared to DFS and IS groups, respectively.Conclusion: Salt fortification with iron, iodine, folate, and Vitamin B12 is feasible and has the potential to increase the serum ferritin, Vitamin B12 and folate levels with subsequent improvement of haemoglobin levels of individuals with relatively low haemoglobin.ClinicalTrial.org Number: NCT04404751.Keywords: iron-deficiency anemia, iodine, iron, vitamin B12, folat

    TARPUKARIU PANEVĖŽYJE STATYTŲ ŠVIETIMO ĮSTAIGŲ ARCHITEKTŪRA / THE ARCHITECTURE OF EDUCATIONAL INSTITUTIONS BUILT DURING THE INTERWAR PERIOD IN THE CITY OF PANEVĖŽYS

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    The buildings of educational institutions built during the interwar period in Panevėžys are a unique part of the city‘s architectural heritage. Over a relatively short period in this city there where built quite a lot buildings for the educational institutions. Despite that, the architecture of these buildings is not analyzed thoroughly in the general context of lithuanian interwar architecture. The main purpose of this paper is to try to analyze the development of the architecture of educational institutions built during the interwar in Panevėžys. Santrauka Tarpukariu Panevėžyje statytų švietimo įstaigų architektūra yra išskirtinė miesto architektūrinio paveldo dalis. Per ganą trumpą tarpukario laikotarpį Panevėžyje švietimo įstaigų pastatų buvo pastatyta daugiau negu bet kurio kito visuomeninių pastatų tipo. Tačiau šis Panevėžio tarpukario architektūrinis palikimas bendrame Lietuvos architektūros istorijos kontekste kol kas nebuvo plačiau analizuotas. Straipsnio tikslas – nuosekliai atskleisti, kaip kito tarpukariu Panevėžyje statytų ar planuotų statyti švietimo įstaigų architektūrinė raiška, kokių bruožų ji įgavo. Į šį tikslą straipsnyje bandoma atsakyti analizuojant tiriamuoju laikotarpiu mieste pastatytų ar neįgyvendintų švietimo įstaigų pastatų architektūrą, taikant formaliąją ir istorinę analizes. Reikšminiai žodžiai: Panevėžys, Panevėžio architektūra, tarpukaris, tarpukario architektūra, švietimo įstaigos, mokyklos, švietimo įstaigų architektūra, mokyklų architektūra
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