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

Spatial enhancer clustering and regulation of enhancer-proximal genes by cohesin

In addition to mediating sister chromatid cohesion during the cell cycle, the cohesin complex associates with CTCF and with active gene regulatory elements to form long-range interactions between its binding sites. Genome-wide chromosome conformation capture had shown that cohesin's main role in interphase genome organization is in mediating interactions within architectural chromosome compartments, rather than specifying compartments per se. However, it remains unclear how cohesin-mediated interactions contribute to the regulation of gene expression. We have found that the binding of CTCF and cohesin is highly enriched at enhancers and in particular at enhancer arrays or “super-enhancers” in mouse thymocytes. Using local and global chromosome conformation capture, we demonstrate that enhancer elements associate not just in linear sequence, but also in 3D, and that spatial enhancer clustering is facilitated by cohesin. The conditional deletion of cohesin from noncycling thymocytes preserved enhancer position, H3K27ac, H4K4me1, and enhancer transcription, but weakened interactions between enhancers. Interestingly, ∼50% of deregulated genes reside in the vicinity of enhancer elements, suggesting that cohesin regulates gene expression through spatial clustering of enhancer elements. We propose a model for cohesin-dependent gene regulation in which spatial clustering of enhancer elements acts as a unified mechanism for both enhancer-promoter “connections” and “insulation.

Cohesin-based chromatin interactions enable regulated gene expression within pre-existing architectural compartments

Chromosome conformation capture approaches have shown that interphase chromatin is partitioned into spatially segregated Mb-sized compartments and sub-Mb-sized topological domains. This compartmentalization is thought to facilitate the matching of genes and regulatory elements, but its precise function and mechanistic basis remain unknown. Cohesin controls chromosome topology to enable DNA repair and chromosome segregation in cycling cells. In addition, cohesin associates with active enhancers and promoters and with CTCF to form long-range interactions important for gene regulation. Although these findings suggest an important role for cohesin in genome organization, this role has not been assessed on a global scale. Unexpectedly, we find that architectural compartments are maintained in non-cycling mouse thymocytes after genetic depletion of cohesin in vivo. Cohesin was however required for specific long-range interactions within compartments where cohesin-regulated genes reside. Cohesin depletion diminished interactions between cohesin-bound sites, while alternative interactions between chromatin features associated with transcriptional activation and repression became more prominent, with corresponding changes in gene expression. Our findings indicate that cohesin-mediated long-range interactions facilitate discrete gene expression states within pre-existing chromosomal compartments

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