61 research outputs found
Final Report of the ASCOBANS Intersessional Working Group on the Assessment of Acoustic Disturbance
Homogenous Pd-Catalyzed Asymmetric Hydrogenation of Unprotected Indoles: Scope and Mechanistic Studies
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The Director of Planning and Operation Research Department, Naval Inventory Control Point (NAVICP) Code M041, requested a study to compare the performance of two sets of inventory control procedures for managing high-cost repairable items. One of these sets is embedded in the Navy's existing wholesale inventory control system. The procedures of this set characterize a periodic review process, which calculates four decision variables in order to manage Navy inventories. These variables represent how much to order, how much to repair, when to order, and when to repair. The other set of procedures are adapted from a commercial software package called Bandwidth Management developed by Stewart- Frazier Tools Inc. Two versions of these latter procedures are modeled in this thesis. These procedures characterize a periodic review process, which calculates three decision variables. These variables represent how much to deliver, how much to repair, and when to repair. This thesis uses simulation to model the two sets of procedures and to compare their performance with respect to three formal measures of effectiveness adopted by NAVICP: Supply Material Availability (SMA), Average Delay for a Delayed Requisition (ADDR), and Average Monthly Investment Level (AMIL). The comparison results of the thesis indicate that the existing Navy inventory procedures generate better performance in all three formal measures of effectiveness.http://archive.org/details/acomparisonofnlt1094532757NAU.S. Navy (U.S.N.) author.Approved for public release; distribution is unlimited
Oral Communication : Hits identified by high-throughput screening at the non-desensitizing S15V-rP2X3 receptor
Oral Communication : Hits identified by high-throughput screening at the non-desensitizing S15V-rP2X3 receptor
The epidemiology of osteoporosis - Bone Evaluation Study (BEST): An analysis of routine health insurance data | Epidemiologie der Osteoporose: Bone Evaluation Study Eine Analyse von Krankenkassen-Routinedaten
Characterization of the melanocortin-4-receptor nonsense mutation W16X in vitro and in vivo
Characterization of the melanocortin-4-receptor nonsense mutation W16X <em>in vitro</em> and <em>in vivo</em>.
Several genetic diseases are triggered by nonsense mutations leading to the formation of truncated and defective proteins. Aminoglycosides have the capability to mediate a bypass of stop mutations during translation thus resulting in a rescue of protein expression. So far no attention has been directed to obesity-associated stop mutations as targets for nonsense suppression. Herein, we focus on the characterization of the melanocortin-4-receptor (MC4R) nonsense allele W16X identified in obese subjects. Cell culture assays revealed a loss-of-function of Mc4r(X16) characterized by impaired surface expression and defect signaling. The aminoglycoside G-418 restored Mc4r(X16) function in vitro demonstrating that Mc4r(X16) is susceptible to nonsense suppression. For the evaluation of nonsense suppression in vivo, we generated a Mc4r(X16) knock-in mouse line by gene targeting. Mc4r(X16) knock-in mice developed hyperphagia, impaired glucose tolerance, severe obesity and an increased body length demonstrating that this new mouse model resembles typical characteristics of Mc4r deficiency. In a first therapeutic trial, the aminoglycosides gentamicin and amikacin induced no amelioration of obesity. Further experiments with Mc4r(X16) knock-in mice will be instrumental to establish nonsense suppression for Mc4r as an obesity-associated target gene expressed in the central nervous system
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