Optimal control of single-server queueing networks

A general single-server queueing network model is considered. It is well-known that an optimal policy is determined by the largest-index policy. There is an index for each given queue and one allocates the server to a queue with largest current index. Using discounted dynamic programming we give a new and short proof of this result and derive some characterizations and bounds of the indices. Moreover, it is shown that an approximate largest-index policy yields an approximately optimal policy. These results lead to efficient methods for computing the indices. In particular, we present a general largest-remaining-index method.     

Parabolic quantitative structure-activity relationships and photodynamic therapy: application of a three-compartment model with clearance to the in vivo quantitative structure-activity relationships of a congeneric series of pyropheophorbide derivatives used as photosensitizers for photodynamic therapy

An open three-compartment pharmacokinetic model was applied to the in vivo quantitative structure-activity relationship (QSAR) data of a homologous series of pyropheophorbide photosensitizers for photodynamic therapy (PDT). The physical model was a lipid compartment sandwiched between two identical aqueous compartments. The first compartment was assumed to clear irreversibly at a rate K0. The measured octanol-water partition coefficients, P(i) (where i is the number of carbons in the alkyl chain) and the clearance rate K0 determined the clearance kinetics of the drugs. Solving the coupled differential equations of the three-compartment model produced clearance kinetics for each of the sensitizers in each of the compartments. The third compartment was found to contain the target of PDT. This series of compounds is quite lipophilic. Therefore these drugs are found mainly in the second compartment. The drug level in the third compartment represents a small fraction of the tissue level and is thus not accessible to direct measurement by extraction. The second compartment of the model accurately predicted the clearance from the serum of mice of the hexyl ether of pyropheophorbide a, one member of this series of compounds. The diffusion and clearance rate constants were those found by fitting the pharmacokinetics of the third compartment to the QSAR data. This result validated the magnitude and mechanistic significance of the rate constants used to model the QSAR data. The PDT response to dose theory was applied to the kinetic behavior of the target compartment drug concentration. This produced a pharmacokinetic-based function connecting PDT response to dose as a function of time postinjection. This mechanistic dose-response function was fitted to published, single time point QSAR data for the pheophorbides. As a result, the PDT target threshold dose together with the predicted QSAR as a function of time postinjection was found.     

Automated Solid‐Phase Synthesis of a β‐(1,3)‐Glucan Dodecasaccharide

β‐Glucans are a group of structurally heterogeneous polysaccharides found in bacteria, fungi, algae and plants. β‐(1,3)‐D ‐Glucans have been studied in most detail due to their impact on the immune system of vertebrates. The studies into the immunomodulatory properties of these glucans are typically carried out with isolates that contain a heterogeneous mixture of polysaccharides of different chain lengths and varying degrees of branching. In order to determine the structure–activity relationship of β‐(1,3)‐glucans, access to homogeneous, structurally‐defined samples of these oligosaccharides that are only available through chemical synthesis is required. The syntheses of β‐glucans reported to date rely on the classical solution‐phase approach. We describe the first automated solid‐phase synthesis of a β‐glucan oligosaccharide that was made possible by innovating and optimizing the linker and glycosylating agent combination. A β‐(1,3)‐glucan dodecasaccharide was assembled in 56 h in a stereoselective fashion with an average yield of 88 % per step. This automated approach provides means for the fast and efficient assembly of linker‐functionalized mono‐ to dodecasaccharide β‐(1,3)‐glucans required for biological studies.     

Highly Efficient Synthesis of Multiantennary Bisected N‐glycans Based on Imidates

The occurrence of N‐glycans with a bisecting GlcNAc modification on glycoproteins has many implications in developmental and immune biology. However, these particular N‐glycans are difficult to obtain either from nature or through synthesis. We have developed a flexible and general method for synthesizing bisected N‐glycans of the complex type by employing modular TFAc‐protected donors for all antennae. The TFAc‐protected N‐glycans are suitable for the late introduction of a bisecting GlcNAc. This integrated strategy permits for the first time the use of a single approach for multiantennary N‐glycans as well as their bisected derivatives via imidates, with unprecedented yields even in a one‐pot double glycosylation. With this new method, rare N‐glycans of the bisected type can be obtained readily, thereby providing defined tools to decipher the biological roles of bisecting GlcNAc modifications.     

Progress toward developing a carbohydrate-conjugate vaccine against Clostridium difficile ribotype 027: synthesis of the cell-surface polysaccharide PS-I repeating unit

Clostridium difficile strain ribotype 027 is a hypervirulent pathogen that is responsible for recent, severe outbreaks of serious nosocomial infections. As a foundation for the development of a preventative carbohydrate-based vaccine, we have synthesized a pentasaccharide cell wall repeating unit from PS-I unique to this strain, by the linear assembly of four monosaccharide building blocks.     

Numerical Simulation of Turbulent Flow and Heat Transfer in a Three-Dimensional Channel Coupled with Flow Through Porous Structures

This study investigates numerically the turbulent flow and heat transfer characteristics of a T-junction mixing, where a porous media flow is vertically discharged in a 3D fully developed channel flow. The fluid equations for the porous medium are solved in a pore structure level using an Speziale, Sarkar and Gatski turbulence model and validated with open literature data. Overall, two types of porous structures, consisted of square pores, are investigated over a wide range of Reynolds numbers: an in-line and a staggered pore structure arrangement. The flow patterns, including the reattachment length in the channel, the velocity field inside the porous medium as well as the fluctuation velocity at the interface, are found to be strongly affected by the velocity ratio between the transversely interacting flow streams. In addition, the heat transfer examination of the flow domain reveals that the temperature distribution in the porous structure is more uniform for the staggered array. The local heat transfer distributions inside the porous structure are also studied, and the general heat transfer rates are correlated in terms of area-averaged Nusselt number accounting for the effects of Reynolds number, velocity ratio as well as the geometrical arrangement of the porous structures.     

Both systemic and local application of Granulocyte-colony stimulating factor (G-CSF) is neuroprotective after retinal ganglion cell axotomy

Background  

The hematopoietic Granulocyte-Colony Stimulating Factor (G-CSF) plays a crucial role in controlling the number of neutrophil progenitor cells. Its function is mediated via the G-CSF receptor, which was recently found to be expressed also in the central nervous system. In addition, G-CSF provided neuroprotection in models of neuronal cell death. Here we used the retinal ganglion cell (RGC) axotomy model to compare effects of local and systemic application of neuroprotective molecules.     

Darstellung und Kristallstruktur von (NH4)2[V(NH3)Cl5]. Die Kristallchemie der Salze (NH4)2[V(NH3)Cl5], [Rh(NH3)5Cl]Cl2 und M2VXCl5 mit M = K,NH4, Rb,Cs und X = Cl,O

Preparation and Crystal Structure of (NH₄)₂[V(NH₃)Cl₅]. The Crystal Chemistry of the Compounds (NH₄)₂[V(NH₃)Cl₅], [Rh(NH₃)₅Cl]Cl₂, and M₂VXCl₅ with M = K, NH₄, Rb, Cs and X ? Cl, O (NH₄)₂[V(NH₃)Cl₅] crystallizes like [Rh(NH₃)₅Cl]Cl₂ in the orthorhombic space group Pnma with Z = 4. The compounds are built up by isolated NH₄⁺ or Cl^? and complex MX₅Y ions. The following distances have been observed: V? N: 213.8, V? Cl: 235.8–239.1, Rh? N: 207.1–208.5, Rh? Cl: 235.5 pm. Both structures differ from the K₂PtCl₆ type mainly in the ordering of the MX₅Y polyhedra. The compounds M₂VCl₆ and M₂VOCl₅ with M = K, NH₄, Rb, and Cs crystallize with exception of the orthorhombic K₂VOCl₅ in the K₂PtCl₆ type. The ordering of the MX₅Y polyhedra in the compounds (NH₄)₂[V(NH₃)Cl₅], [Rh(NH₃)₅Cl]Cl₂ and K₂VOCl₅ enables a closer packing.