The performance of the supply chain: Strategical harmonization

On this paperwork, we define the strategy of the logistic chain and we explain the way in which the creation of a strategical harmonization between the competitive strategy of the companz and the strategz of the logistic chain affects the performance of the whole company. We also analyse the importance of the extension of strategical harmonization from an operation inside the companyto all the levels of logistic chain. This paperwork propose: explaining why obtaining a strategical harmonization is critical for the succes of a whole company, the description of the way in which a company realize a strategical harmonization between the strategy of the logistic chain and it’s competitional strategy and the disscution about the importance of expanding the strategical harmonization over the logistic chain.competitional strategies, logistics, strategical harmonization, consumer’s needs, values chain.

Romania’s Pension System: The Weight of the Past

In Romania before 1989, as elsewhere in the Soviet world, retirement support was one of the few rewards that the regime offered its citizens. Retirement provisions were based exclusively transfers, through the State, from the current working population to the pensioners. Technically, the system was a Pay As You Go System. The difference was that retirement provisions, like every other facet of the economy, were planned. Workers did not choose, but were told, when to retire. Early retirment was not envisioned. Sick live was strictly controlled and limited. There was no unemployment, and the penalties for any enterprise which evaded payments to the system were prohibitive (The State Bank was simply prohibited from paying wages until wage taxes had been paid). Transfers in cash and kind to the pensioners were strictly limited to the resources available. As a consequence, before 1989, Romania.s retirement system can be considered to have been consistently in excess. In the years which followed the overthrow of Nicolae Ceausescu, the public retirement system lost the constraints imposed by a command economy, and its implicit tensions became manifest. As the dispersion of wages increased under the pressure of even proto-market forces, disparities between benefits and contributions appeared, and the pressure for tax evasion grew. Tax discipline deteriorated. Furthermore, the new Government extended the pension system it had inherited, increasing the benefits and relaxing the qualifications, in response to political pressures. The result was that the system became fiscally imbalanced, and that, paradoxically, though privileges multiplied, actual average benefits declined. By 1997, the public pension system was in deficit, and the average real benefit had fallen to 45 % of its level in 1990. In 1998, Romania began an ambitious reform of its pension system, and proceed with a plan to introduce by stages a completely new three-pillar system. The form entailed a radical change of the public pension system (including the transition to a "point" system, unification of regimes, and increases in retirement ages), and a diversion of one third of the mandatory social security tax to a new private system of Universal Pension Funds. This paper presents and analyses the weight of the past. It describes the institutional weaknesses of the pre-reform system and analyses the demographic pressures threatening it. It concludes with a calculation of the implicit debt of the pre-reform system in 1997.Romania, pension systems

Clinical evaluation of the C-MAC D-Blade videolaryngoscope in severely obese patients: a pilot study

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Lineage-specific compaction of Tcrb requires a chromatin barrier to protect the function of a long-range tethering element

Gene regulation relies on dynamic changes in three-dimensional chromatin conformation, which are shaped by composite regulatory and architectural elements. However, mechanisms that govern such conformational switches within chromosomal domains remain unknown. We identify a novel mechanism by which cis-elements promote long-range interactions, inducing conformational changes critical for diversification of the TCRβ antigen receptor locus (Tcrb). Association between distal Vβ gene segments and the highly expressed DβJβ clusters, termed the recombination center (RC), is independent of enhancer function and recruitment of V(D)J recombinase. Instead, we find that tissue-specific folding of Tcrb relies on two distinct architectural elements located upstream of the RC. The first, a CTCF-containing element, directly tethers distal portions of the Vβ array to the RC. The second element is a chromatin barrier that protects the tether from hyperactive RC chromatin. When the second element is removed, active RC chromatin spreads upstream, forcing the tether to serve as a new barrier. Acquisition of barrier function by the CTCF element disrupts contacts between distal Vβ gene segments and significantly alters Tcrb repertoires. Our findings reveal a separation of function for RC-flanking regions, in which anchors for long-range recombination must be cordoned off from hyperactive RC landscapes by chromatin barriers

Intellectual disability-associated factor Zbtb11 cooperates with NRF-2/GABP to control mitochondrial function

Zbtb11 is a conserved transcription factor mutated in families with hereditary intellectual disability. Its precise molecular and cellular functions are currently unknown, precluding our understanding of the aetiology of this disease. Using a combination of functional genomics, genetic and biochemical approaches, here we show that Zbtb11 plays essential roles in maintaining the homeostasis of mitochondrial function. Mechanistically, we find Zbtb11 facilitates the recruitment of nuclear respiratory factor 2 (NRF-2) to its target promoters, activating a subset of nuclear genes with roles in the biogenesis of respiratory complex I and the mitoribosome. Genetic inactivation of Zbtb11 resulted in a severe complex I assembly defect, impaired mitochondrial respiration, mitochondrial depolarisation, and ultimately proliferation arrest and cell death. Experimental modelling of the pathogenic human mutations showed these have a destabilising effect on the protein, resulting in reduced Zbtb11 dosage, downregulation of its target genes, and impaired complex I biogenesis. Our study establishes Zbtb11 as an essential mitochondrial regulator, improves our understanding of the transcriptional mechanisms of nuclear control over mitochondria, and may help to understand the aetiology of Zbtb11-associated intellectual disability.</p

Nuclear Genetic Regulation of the Human Mitochondrial Transcriptome

Mitochondria play important roles in cellular processes and disease, yet little is known about how the transcriptional regime of the mitochondrial genome varies across individuals and tissues. By analyzing &gt;11,000 RNA-sequencing libraries across 36 tissue/cell types, we find considerable variation in mitochondrial-encoded gene expression along the mitochondrial transcriptome, across tissues and between individuals, highlighting the importance of cell-type specific and post-transcriptional processes in shaping mitochondrial-encoded RNA levels. Using whole-genome genetic data we identify 64 nuclear loci associated with expression levels of 14 genes encoded in the mitochondrial genome, including missense variants within genes involved in mitochondrial function (TBRG4, MTPAP and LONP1), implicating genetic mechanisms that act in trans across the two genomes. We replicate ~21% of associations with independent tissue-matched datasets and find genetic variants linked to these nuclear loci that are associated with cardio-metabolic phenotypes and Vitiligo, supporting a potential role for variable mitochondrial-encoded gene expression in complex disease