Supreme Command and Strategic Purpose in Iraq; Strategic Insights: v.2, issue 2 (February 2003)

This article appeared in Strategic Insights (February 2003), v.2 no.2At a time when the talk of war against Iraq is so casually bandied about in the United States, Elliot A. Cohen's book, Supreme Command, is timely and essential reading for supporters and opponents of that war. Cohen studies four great statesmen--Abraham Lincoln, Georges Clemenceau, Winston Churchill, and David Ben Gurion. One of his major conclusions is that they succeeded in their role because they immersed themselves in the conduct of war; they mastered their military briefs as thoroughly as they did their civilian ones; and they demanded and expected from their military subordinates a candor as bruising as it was necessary. While the study of those leaders is significant for the current and future generations of leaders, it is equally important to examine how President George W. Bush conducts himself in the seemingly definite war against Iraq. He has the benefit of Cohen's sage observations, since he is reported to have read Supreme Command. Applying the preceding to the Iraqi situation Bush currently faces, the need for having a clear strategic concept--I prefer the phrase strategic purpose--is vital. We do not know what President Bush has learned from Cohen's book, and what lessons he has drawn from it for his upcoming involvement in a military campaign against Iraq. However, if Cohen's observation about the significance of having a right strategic purpose is correct, then military action against Iraq should never take place

Structural dynamics of the selectivity filter in HCN1 ion channel

Les canaux HCN (cycliques nucléotidiques) activés par hyperpolarisation appartiennent à la superfamille des canaux cationiques voltage-dépendants et sont responsables de la génération de courant drôle (If) dans les cellules cardiaques et neuronales. Malgré la similitude structurelle globale avec le potassium voltage-dépendant (Kv) et les canaux ioniques cycliques nucléotidiques (CNG), ils montrent un modèle de sélectivité distinctif pour les ions K+ et Na+. Plus précisément, leur perméabilité accrue aux ions Na+ est essentielle à son rôle dans la dépolarisation des membranes cellulaires. Ils sont également l'une des seules protéines connues à sélectionner entre les ions Na+ et Li+, faisant des HCN des canaux semi-sélectifs. Ici, nous étudions les propriétés de sélectivité uniques des canaux HCN à l'aide de simulations de dynamique moléculaire. Nos simulations suggèrent que le pore HCN1 est très flexible et dilaté par rapport aux canaux Kv et qu'il n'y a qu'un seul site de liaison ionique stable dans le filtre de sélectivité qui les distingue des canaux Kv et CNG. Nous observons également que la coordination et l'hydratation des ions diffèrent dans le filtre de sélectivité de HCN1 par rapport aux canaux Kv et CNG. De plus, la coordination des ions K+ par les groupes carbonyle du filtre de sélectivité est plus stable par rapport aux ions Na+ et Li+, ce qui peut expliquer les propriétés de sélectivité distinctes du canal.Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels belong to the voltage-gated cation channel superfamily and are responsible for the generation of funny current (If) in cardiac and neuronal cells. Despite the overall structural similarity to voltage-gated potassium (Kv) and cyclic nucleotide-gated (CNG) ion channels, they show distinctive selectivity pattern for K+ and Na+ ions. Specifically, their increased permeability to Na+ ions is critical to its role in depolarizing cellular membranes. They are also one of the only known proteins to select between Na+ and Li+ ions, making HCNs semi-selective channels. Here we investigate the unique selectivity properties of HCN channels using molecular dynamics simulations. Our simulations suggest that the HCN1 pore is very flexible and dilatated compared to Kv channels and that there is only one stable ion binding site within the selectivity filter which discriminates them from both Kv and CNG channels. We also observe that ion co-ordination and hydration differ within the selectivity filter of HCN1 compared to Kv and CNG channels. Additionally, the co-ordination of K+ ions by the carbonyl groups of the selectivity filter is more stable compared to Na+ and Li+ ions, which may explain the channel's distinct selectivity properties

A Decision Support System for Dynamic Integrated Project Scheduling and Equipment Operation Planning

Common practice in scheduling under limited resource availability is to first schedule activities with the assumption of unlimited resources, and then assign required resources to activities until available resources are exhausted. The process of matching a feasible resource plan with a feasible schedule is called resource allocation. Then, to avoid sharp fluctuations in the resource profile, further adjustments are applied to both schedule and resource allocation plan within the limits of feasibility constraints. This process is referred to as resource leveling in the literature. Combination of these three stages constitutes the standard approach of top-down scheduling. In contrast, when scarce and/or expensive resource is to be scheduled, first a feasible and economical resource usage plan is established and then activities are scheduled accordingly. This practice is referred to as bottom-up scheduling in the literature. Several algorithms are developed and implemented in various commercial scheduling software packages to schedule based on either of these approaches. However, in reality resource loaded scheduling problems are somewhere in between these two ends of the spectrum. Additionally, application of either of these conventional approaches results in just a feasible resource loaded schedule which is not necessarily the cost optimal solution. In order to find the cost optimal solution, activity scheduling and resource allocation problems should be considered jointly. In other words, these two individual problems should be formulated and solved as an integrated optimization problem. In this research, a novel integrated optimization model is proposed for solving the resource loaded scheduling problems with concentration on construction heavy equipment being the targeted resource type. Assumptions regarding this particular type of resource along with other practical assumptions are provided for the model through inputs and constraints. The objective function is to minimize the fraction of the execution cost of resource loaded schedule which varies based on the selected solution and thus, considered to be the model's decision making criterion. This fraction of cost which hereafter is referred to as operation cost, encompasses four components namely schedule delay cost, shipping, rental and ownership costs for equipment

Direct regulation of inward rectifier K+ (Kir) channel by endocannabinoids

This thesis represents the culmination of the main project I have undertaken during my master's program. It is important to note that additional data collection and analysis were conducted by intern students under my supervision, which will be integrated into a forthcoming manuscript where I will be credited as the first co-author. Due to space and focus limitations of this thesis, these additional findings have not been included here.La famille des canaux potassiques à rectification entrante (Kir), exprimée de manière ubiquitaire, repolarise et maintient le gradient de tension à travers les membranes des cellules excitables et non-excitables. Les canaux Kir sont fortement régulés par divers lipides membranaires, tels que les phosphoinositides, les phospholipides anioniques secondaires, le cholestérol, le Coenzyme A (CoA) à longue chaîne et l'acide arachidonique. Kir2.1 est fortement exprimé dans le tissu musculaire strié des cellules cardiaques auriculaires et ventriculaires. Il joue un rôle essentiel dans la régulation du potentiel de membrane au repos et de la contraction des cellules musculaires cardiaques et lisses en générant le courant K+ à rectification entrante (IK1). (IK1). Les mutations de Kir2.1 avec perte de fonction sont à l'origine du syndrome d'Andersen-Tawil (ATS). Par conséquent, l'altération de la fonction de Kir2.1 est un déterminant essentiel au bon fonctionnement du cœur. Les endocannabinoïdes sont une classe spéciale de lipides naturellement exprimés dans une variété de cellules, y compris les cellules cardiaques, neuronales et immunitaires. Le système endocannabinoïde, y compris les récepteurs cannabinoïdes (CBR), agit comme un système de réponse au stress qui s'active. Des études menées chez l'animal et chez l'homme suggèrent que la modulation pharmacologique de ce système pourrait représenter une nouvelle approche thérapeutique. Cependant, ces dernières années, il est devenu clair que si les endocannabinoïdes peuvent déclencher des changements de signalisation en aval par l'intermédiaire des CBR, ils peuvent également interagir directement avec les canaux ioniques indépendamment des CBR pour moduler la fonction cellulaire. Dans cette étude, nous avons utilisé la technique de double électrode en voltage imposé pour examiner les effets d'un panel d'endocannabinoïdes sur la fonction de Kir2.1. Nous avons montré qu'un sous-ensemble d'endocannabinoïdes, mais pas tous, peut réguler la fonction de Kir2.1 à des degrés divers, indépendamment des CBR. Nous avons également démontré que les endocannabinoïdes peuvent également réguler les protéines mutées menant à l'ATS (G144S et V302M). Nous avons également observé que l'effet des endocannabinoïdes n'est pas conservé parmi les membres de la famille Kir, avec des différences observées entre les canaux Kir2.1, Kir4.1 et Kir7.1. Ces résultats pourraient avoir des implications plus larges pour les fonctions des cellules cardiaques, neuronales et immunitaires. Mots clés : Kir2.1, Endocannabinoïdes, LQT7, Rectification entrante, G144S, Kir7.1, Kir4.1The ubiquitously expressed family of inward rectifier potassium (Kir) channels repolarizes and maintains the voltage gradient across excitable and non-excitable cell membranes. Kir channels are highly regulated by various membrane lipids, such as phosphoinositides, secondary anionic phospholipids, cholesterol, long chain acyl- Coenzyme A (CoA), and arachidonic acid. Kir2.1 is highly expressed in striated muscle tissue of atrial and ventricular heart cells. It is critically involved in regulating the resting membrane potential and contraction of cardiac and smooth muscle cells through the generation of the current IK1. Loss-of-function mutations in Kir2.1 cause Andersen-Tawil syndrome (ATS). Therefore, altered Kir2.1 function is a critical determinant of proper heart function. Endocannabinoids are a special class of lipids that are naturally expressed in a variety of cells, including cardiac, neuronal, and immune cells. The endocannabinoid system, including cannabinoid receptors (CBRs), acts as a stress response system that is activated. Studies in both animals and humans suggest that pharmacological modulation of this system might represent a novel approach to treatment. However, in recent years, it is becoming clear that while endocannabinoids can trigger downstream signaling changes through CBRs, they can also directly interact with ion channels independently of CBRs to modulate cellular function. In this study, we used the electrophysiology technique called two-electrode-voltage-clamp (TEVC) in combination with mutagenesis studies to examine the effects of a panel of endocannabinoids on the function of Kir2.1. We showed that a subset of endocannabinoids, but not all, can regulate the Kir2.1 function to varying degrees, independent of CBRs. We also demonstrated that endocannabinoids can also regulate mutants linked with ATS (G144S and V302M). We also observed that the effect of endocannabinoids is not conserved among Kir family members, with differences observed between Kir2.1, Kir4.1 and Kir7.1 channels. These findings could have broader implications for cardiac, neuronal, and immune cell functions. Key words: Kir2.1, Endocannabinoids, LQT7, Inward rectification, G144S, Kir7.1, Kir4.

The effect of surface treatment with Er:YAG laser on shear bond strength of orthodontic brackets to fi ber-reinforced composite

Objectives: This study aimed to investigate the effect of surface treatment with Er:YAG laser on shear bond streng- th (SBS) of orthodontic brackets to fi ber-reinforced composite (FRC). Study Design: Ninety human premolars were randomly divided into six groups of 15. FRC bars were bonded to the teeth with a fl owable composite (FC) and then underwent following treatments. In group 1 no further treatment was performed. In group 2 the FRC surfaces were covered by FC. An Er:YAG laser was employed to treat FRCs in groups 3 ( 200 mJ/10 Hz) and 4 (300 mJ/15 Hz). The FRC strips in groups 5 and 6 were fi rst covered by FC and then irradiated with Er:YAG laser at 200 mJ/10 Hz (group 5) or 300 mJ/15 Hz (group 6). Stainless steel brackets were bonded to FRCs using a light-cure adhesive system. After 24 hours, the samples were tested for SBS and the adhesive remnant index (ARI) scores were determined. Results: There was a signifi cant difference in SBS among the study groups (P <0.001). Pairwise comparisons in- dicated that SBS was signifi cantly lower in group 1 compared to all other groups (p<0.05) except group 2. Bond strength in group 6 was signifi cantly greater than all the study groups (p<0.05) except group 5. No signifi cant di- fference was found in ARI scores among the groups. Conclusions: Covering the FRC surface by a layer of fl owable composite and then application of Er:YAG laser at 300 mJ/15 Hz could be recommended to increase bond strength of orthodontic attachments to FRC

Structural and Morphological Changes in Human Dentin after Ablative and Subablative Er:YAG Laser Irradiation

Introduction: This study investigated the influence of Erbium-Doped Yttrium Aluminum Garnet (Er:YAG) laser on microhardness, chemical composition and subsurface morphology of dentin cavity walls.Methods: Forty sound human premolars were selected and randomly assigned into four groups. Class V cavities were prepared either with an Er:YAG laser (groups 1 and 2; 15 Hz, 250 mJ for enamel, 10 Hz, 200 mJ for dentin) or with a high speed handpiece (groups 3 and 4). The specimens in groups 1 and 3 served as the control, whereas those in groups 2 and 4 were exposed to subablative laser irradiation following cavity preparation (10 Hz, 50 mJ). After bisecting the specimens, one half was subjected to microhardness assessment and the other half was evaluated by SEM-EDS analysis.Results: Microhardness was significantly greater in the specimens prepared by both ablative and subablative laser irradiation (group 2) than that of the bur-prepared cavities (groups 3 and 4) (P&lt;0.05). The quantity of calcium ion was significantly greater in cavities prepared by the Er:YAG laser (groups 1 and 2) compared to that of the bur cavities (groups 3 and 4) (p&lt;0.05). Subablative irradiation improved microhardness and weight percentage of calcium ion in both laser and bur cavities, but the difference was not significant compared to that of the relevant control group (P&gt;0.05). Conclusion: Cavity preparation with an Er:YAG laser could be considered as an alternative to the conventional method of drilling, as it enhances the mechanical and compositional properties of lased dentin, especially when combined by subablative irradiation

Cost minimisation technique in geo-distributed data centres

Significant growth of Big Data leads to a great opportunity for data analysis. Data centres are continuously becoming more popular. At the same time data centres’ cost are increasing as the amount of data is growing. Simply as Big Data is significantly increasing, data centres are facing new challenges. Hence the idea of geo-distributed data centre is introduced. This project investigates on the main challenges that data centres face and presents an enhanced technique for cost optimisation in geographical distributed data centres. Parameters involved such as task assignment, task placement, big data processing and quality of service are analysed. Analytical evaluation results show that joint parameters technique proposed outperformed separate parameter techniques in some cases even with 20% enhancement. Academic Gurobi solver is used for the evaluation