Generation and characterization of phenylsulfanylcarbene

A photosensitive precursor (1) to phenylsulfanylcarbene 2 has been synthesized. Laser flash photolysis (308 nm) of 1 and chemical trapping studies of 2 are reported. [structure: see text]     

Composition Operators and Endomorphisms

If b is an inner function, then composition with b induces an endomorphism, β, of L^￥(mathbbT){L^infty({mathbb{T}})} that leaves H^￥(mathbbT){H^infty({mathbb{T}})} invariant. We investigate the structure of the endomorphisms of B(L²(mathbbT)){B(L^2({mathbb{T}}))} and B(H²(mathbbT)){B(H^2({mathbb{T}}))} that implement β through the representations of L^￥(mathbbT){L^infty({mathbb{T}})} and H^￥(mathbbT){H^infty({mathbb{T}})} in terms of multiplication operators on L²(mathbbT){L^2({mathbb{T}})} and H²(mathbbT){H^2({mathbb{T}})} . Our analysis, which is based on work of Rochberg and McDonald, will wind its way through the theory of composition operators on spaces of analytic functions to recent work on Cuntz families of isometries and Hilbert C*-modules.     

The multiple roles of computational chemistry in fragment-based drug design

Fragment-based drug discovery (FBDD) represents a change in strategy from the screening of molecules with higher molecular weights and physical properties more akin to fully drug-like compounds, to the screening of smaller, less complex molecules. This is because it has been recognised that fragment hit molecules can be efficiently grown and optimised into leads, particularly after the binding mode to the target protein has been first determined by 3D structural elucidation, e.g. by NMR or X-ray crystallography. Several studies have shown that medicinal chemistry optimisation of an already drug-like hit or lead compound can result in a final compound with too high molecular weight and lipophilicity. The evolution of a lower molecular weight fragment hit therefore represents an attractive alternative approach to optimisation as it allows better control of compound properties. Computational chemistry can play an important role both prior to a fragment screen, in producing a target focussed fragment library, and post-screening in the evolution of a drug-like molecule from a fragment hit, both with and without the available fragment-target co-complex structure. We will review many of the current developments in the area and illustrate with some recent examples from successful FBDD discovery projects that we have conducted.     

Convenient method of synthesizing 3-ethoxycarbonyl indoles

We have developed a convenient two-step procedure for the synthesis of 3-ethoxycarbonyl indoles from commercially available materials. The two-step procedure involves the synthesis of 2-aryl-3-hydroxypropenoic acid ester, followed by a catalytic reduction. This method is efficient, simple, and selective.     

A History of Blast Exposure May Affect the Transmission Properties of Cranial Bone

An individual who has sustained mild traumatic brain injury (mTBI) due to impact is more susceptible to a second concussion for a time, presumably due to the vulnerability of the injured brain tissue. This knowledge informed military guidelines regarding return to duty following blast-related TBI (bTBI). However, bone mechanics studies have shown that bone experiences hysteresis above certain strains as a result of microdamage, which suggests that blast exposure may also reduce the ability of the cranium itself to protect the brain from another blast. In the present study, the response of deer skull bone to blast wave exposure was measured. Oxy-acetylene driven laboratory scale shock tubes were used to produce realistic blast loading profiles. When a skull was exposed to peak blast pressures of about 600 kPa (measured with the sensor facing the direction of propagation of the blast wave) from a 41 mm diameter shock tube, the peak transmitted pressure gradually increased from 13.1 % to 40.2 % over five trials. This hysteresis was persistent and repeatable but was not observed with more localized loading. Future work could more specifically quantify blast thresholds at which persistent changes could be expected. Results from such work would further inform clinical decisions regarding return to activity following bTBI. The present results show that blast loading history of cranial bone should be understood and controlled in the design of related experiments. The results also underscore the need for accurate material properties and experimental validation of numerical models of the interaction of blast waves with the cranium.     

Role of magnetic shear on the electrostatic current driven ion-cyclotron instability in the presence of parallel electric field

Recent observation and theoretical investigations have led to the significance of electrostatic ion cyclotron (EIC) waves in the electrodynamics of acceleration process. The instability is one of the fundamental of a current carrying magnetized plasma. The EIC instability has the lowest threshold current among the current driven instabilities. On the basis of local analysis where inhomogeneities like the magnetic shear and the finite width current channel, have been ignored which is prevalent in the magnetospheric environment. On the basis of non-local analysis interesting modification has been incorporated by the inclusion of magnetic shear. In this paper we provide an analytical approach for the non-local treatment of current driven electrostatic waves in presence of parallel electric field. The growth rate is significantly influenced by the field aligned electron drift. The presence of electric field enhances the growth of EIC waves while magnetic shear stabilizes the system.     

Manipulation of microparticles using phase-controllable ultrasonic standing waves

A method of manipulating microparticles in a liquid using ultrasound is proposed and demonstrated. An ultrasonic standing wave with nodal planes whose positions are controllable by varying the relative phase of two applied sinusoidal signals is generated using a pair of acoustically matched piezoelectric transducers. The resulting acoustic radiation force is used to trap micron scale particles at a series of arbitrary positions (determined by the relative phase) and then move them in a controlled manner. This method is demonstrated experimentally and 5 μm polystyrene particles are trapped and moved in one dimension through 140 μm.     

Targeted protein oxidation using a chromophore-modified rapamycin analog

Chemically induced dimerization of FKBP and FRB using rapamycin and rapamycin analogs has been utilized in a variety of biological applications. Formation of the FKBP-rapamycin-FRB ternary complex is typically used to activate a biological process and this interaction has proven to be essentially irreversible. In many cases, it would be beneficial to also have temporal control over deactivating a biological process once it has been initiated. Thus, we developed the first reactive oxygen species-generating rapamycin analog toward this goal. The BODIPY-rapamycin analog BORap is capable of dimerizing FKBP and FRB to form a ternary complex, and upon irradiation with 530 nm light, generates singlet oxygen to oxidize and inactivate proteins of interest fused to FKBP/FRB.

Utilization of a ROS-generating chromophore for the development of reversible control of rapamycin-induced protein dimerization via targeted oxidation.     

The development of information storage materials — How microscopy can help?

The response of giant magnetoresistance (GMR) devices depends critically on the film microstructure, with parameters such as layer thickness and interfacial abruptness being crucial. This paper presents results obtained using high resolution electron microscopy (HREM), chemical mapping and atom probe microanalysis. Local variations in the magnetic properties are induced by the microstructure and also when the films are patterned to form small elements. These lead to changes in the magnetization reversal mechanism. Some results of the studies of the magnetization reversal carried out using in situ in Lorentz transmission electron microscopy (LTEM) magnetizing experiments are also included.