A COMPARATIVE ANALYSIS OF AN ORIGINAL AND A POST-HOC APPLICATION OF LEAN SIX SIGMA METHODOLOGY

Current society develops faster and faster every day with customers\u27 demands increasing rapidly. Decreasing time for product development and enhancing customer satisfaction are becoming more significant. In the business world, there is no industry that could exist without an efficient supply chain. In the fierce competitive environment of today, the supply chain must address potential problems and risks that may exist and assure continuous improvement. One common supply chain management practice in many industries is to apply lean methodology to the supply chain model in order to maximize the customers\u27 value and eliminate waste. By eliminating waste, the process can be expedited, a company\u27s costs reduced and profitability improved. Today, in many industries, applying other principles to the supply chain is very popular. Information Technology software flow synchronizes the physical flow with the data flow and in order to expedite the supply chain process. Application of information technology and Six Sigma philosophy has also become a part of supply chain management. Lean Six Sigma principles utilize analytical methods to optimize each link of the supply chain to promote a winning customer/supplier model. Poor supply chain management will harm the health of any business process and could lead to high losses while a well managed and structured supply chain will support a positive direction furthering a company\u27s success. This study analyzes Lean and Six Sigma support of the Supply Chain from multiple angles and addresses certain issues that potentially exist. It is based on an original case study to reduce package Engineering Change lead time and details the revisions the author has taken to improve on that work. The corresponding data analysis from the refined project results show how the package EC process could be improved, the value add based upon the post hoc analysis and the methodology used to benefit the high technology supply chain and overall business performance

Molecular insights into pyruvate-sensing of the LytS/LytTR-type BtsS/BtsR signaling cascade of Escherichia coli

LytS/LytTR-type histidine kinase/response regulator systems regulate pathogen-specific mechanisms during infection of human or plant hosts. Escherichia coli has two LytS/LytTR systems, BtsS/BtsR and YpdA/YpdB. The histidine kinase BtsS is a high-affinity sensor for extracellular pyruvate and interacts with response regulator BtsR to activate the expression of btsT, which encodes a symporter for pyruvate and proton. This thesis describes new insights into the molecular mechanism of how pyruvate binding triggers the signal transduction process. It was experimentally shown that BtsS is a seven-helix receptor, with its N-terminus located in the periplasm. Using a screening assay based on site-directed mutagenesis, the pyruvate-binding site was identified within the membrane-spanning domains of BtsS. It is a small cavity, and pyruvate forms interactions with the side chains of arginine 72, arginine 99, cysteine 110, and serine 113, located in the transmembrane helices III, IV and V, respectively. The interactions between pyruvate and these four amino acids were further confirmed by molecular dynamics simulation studies. In addition, three other amino acids in BtsS were found to be important for structure and signal transduction. Arginine 192 (helix VII) plays a role in the interaction with BtsR. Serine 25 (helix I) is important for conformational dynamics, as BtsS variants in which Serine 25 has beenreplaced by alanine or valine maintain the signal transduction system in an ON state. Cysteine 15 is likely involved in the formation of a disulfide bridge, but this is not essential for signal transduction in vivo under the conditions tested. In previous studies, the autophosphorylation activity of BtsS was not detectable. Here, for the first time, BtsS was shown to have very low autophosphorylation activity in the presence of Mg2+-ATP, which was approximately 10-fold higher when Mn2+-ATP was used. The predicted phosphorylation site at histidine 382 was confirmed. Moreover, the autokinase activity of BtsS could be stimulated in the presence of pyruvate. Measurements of in vitro autophosphorylation activity were used as a parameter to determine the molecular effects of individual amino acid replacements in BtsS, and the effects resulted not only in massive changes in activity levels but also in pyruvate-independent activity for many variants. The elucidation of the pyruvate-binding site of BtsS opened the possibility of redesigning BtsS into a sensor of pyruvate-like ligands such as lactate, which can be used as a biosensor in medicine. The required workflow and a high-throughput screening system were established

Analysis on 85 case reports of adverse drug reactions

This study investigated the occurrence and characteristics of adverse drug reactions (ADR) in our hospital and provide references for clinical rational drug use. We collected the 85 case reports of adverse drug reactions in our hospital in 2010 and made retrospective statistical analysis on them. The varieties of anti-infective drugs used are the most used. It also had the highest proportion of adverse drug reactions; the common symptom of adverse drug reactions is skin and accessory damage. Adverse drug reactions are affected by many factors, and relevant departments should strengthen ADR monitoring, to reduce or avoid the occurrence of adverse drug reactions