Deliberately Losing Control of C−H Activation Processes in the Design of Small-Molecule-Fragment Arrays Targeting Peroxisomal Metabolism

Combined photochemical arylation, “nuisance effect” (S_NAr) reaction sequences have been employed in the design of small arrays for immediate deployment in medium-throughput X-ray protein–ligand structure determination. Reactions were deliberately allowed to run “out of control” in terms of selectivity; for example the ortho-arylation of 2-phenylpyridine gave five products resulting from mono- and bisarylations combined with S_NAr processes. As a result, a number of crystallographic hits against NUDT7, a key peroxisomal CoA ester hydrolase, have been identified.     

Biocatalytic Alkylation Cascades: Recent Advances and Future Opportunities for Late-Stage Functionalization

This Concept article describes the latest developments in the emerging area of late-stage biocatalytic alkylation. Central to these developments is the ability to efficiently prepare S-adenosyl methionine (SAM) cofactor analogues and couple this with enzymatic alkyl transfer. Recent developments in the enzymatic synthesis of SAM cofactor analogues are summarized first, followed by their application as alkyl transfer agents catalyzed by methyltransferases (MTases). Second, innovative methods to regenerate SAM cofactors by enzymatic cascades is reported. Finally, future opportunities towards establishing a generalized platform for late-stage alkylation are described.     

THE EFFECT OF GEOMETRY ON THE DEVELOPMENT OF CREEP SINGULAR FIELDS FOR DEFECTS UNDER STEP-LOAD CONTROLLED LOADING

Abstract— The development of singular fields for defects in steadily loaded creeping structures is examined as a function of geometry and crack size using finite-element analyses and results from the literature. Approximations for estimating the time-development of the amplitude of the fields are examined and it is shown that simple approximations are expected to apply for a wide range of geometries. It is shown both theoretically and numerically that plasticity on initial loading produces crack tip fields closer to the steady state condition than those produced elastically.     

Structures at elevated temperatures: How long will they last?

In principle, questions about the behaviour of high-temperature structures can be answered by analysis in conjunction with material creep properties. However, because of the wide range of geometries in use, simplified methods have been developed which avoid lengthy computations yet isolate the important factors controlling component behaviour. This paper describes one approach which is to define a reference stress such that the component life is equal to the life of a simple specimen tested at the reference stress. A substantial body of work has shown that the reference stress can often be established quite simply even for complex components containing cracks. The approach then provides a simple framework for assessing structures which operate at high temperatures.     

John Bowlby (1907–1990): Obituary.

Marks the death of John Bowlby, whose Attachment Theory (AT) has had greater impact on American psychology than any theory of personality development since Freud's. Bowlby believed in the importance of real-life experiences in the etiology of mental disorders, rather than in the fantasies that then-current psychoanalytic theory emphasized. He was convinced of the importance to a child's personality development of interaction with its parents. In 1948, he established a research unit at the Tavistock Clinic to continue his work on the effects of early separation and identified 3 phases of response: protest, despair, and detachment. Inspired by the work of Konrad Lorenz, Bowlby seized on ethology and Darwinian evolutionary theory as the foundation of AT. First applied to social development in infancy, AT is now leading to research in later childhood and adulthood. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

50-nm Self-Aligned and “Standard” T-gate InP pHEMT Comparison: The Influence of Parasitics on Performance at the 50-nm Node

Continued research into the development of III-V high-electron mobility transistors (HEMTs), specifically the minimization of the device gate length, has yielded the fastest performance reported for any three terminal devices to date. In addition, more recent research has begun to focus on reducing the parasitic device elements such as access resistance and gate fringing capacitance, which become crucial for short gate length device performance maximization. Adopting a self-aligned T-gate architecture is one method used to reduce parasitic device access resistance, but at the cost of increasing parasitic gate fringing capacitances. As the device gate length is then reduced, the benefits of the self-aligned gate process come into question, as at these ultrashort-gate dimensions, the magnitude of the static fringing capacitances will have a greater impact on performance. To better understand the influence of these issues on the dc and RF performance of short gate length InP pHEMTs, the authors present a comparison between In_0.7Ga_0.3As channel 50-nm self-aligned and "standard" T-gate devices. Figures of merit for these devices include transconductance greater than 1.9 S/mm, drive current in the range 1.4 A/mm, and fT up to 490 GHz. Simulation of the parasitic capacitances associated with the self-aligned gate structure then leads a discussion concerning the realistic benefits of incorporating the self-aligned gate process into a sub-50-nm HEMT system     

Changes in the size and docosahexaenoic acid content of adipocytes during chick embryo development

The development of adipose tissue in the chick embryo was investigated using two groups of fertile eggs which differed by 1.7-fold in their initial yolk lipid levels. The triacylglycerol content of the subcutaneous adipose depot in both groups increased dramatically from day 12 of the 21-day embryonic period, attaining a maximal value just prior to hatching. During this period, the amount of triacylglycerol deposited in the adipose tissue was very highly correlated with the amount of lipid transferred from the yolk. The triacylglycerol content of the depot was also dependent on the initial yolk lipid content. During the hatching period, the amount of adipose triacylglycerol remained approximately constant in the group with the higher initial yolk lipid content but, in the case of the group with the lower initial yolk lipid levels, decreased by approximately 25%. The size distribution of adipocytes isolated from the tissue was determined by computerized image analysis microscopy. The mean adipocyte diameter increased from approximately 6 to 35 μm between days 12 and 19, irrespective of the initial yolk content, although development within the eggs with the lower initial yolk content resulted in a decrease in cell size over the hatching period. Both the triacylglycerol and phospholipid fractions of the isolated adipocytes contained substantial proportions (approximately 6%, w/w) of docosahexaenoic acid (DHA) at days 12 and 14, and lower levels of this fatty acid at the later stages. The amount (mg/depot) of DHA in adipose triacylglycerol decreased dramatically over the hatching period. The amount (mg/brain) of DHA in brain phospholipid increased by more than 5-fold between day 12 of development and hatching. A possible explanation for the data may be that DHA is preferentially mobilized from adipose tissue in order to deliver the fatty acid to the developing neural tissues in a form suitable for uptake.     

Fixed-wavelength operation of a copper-laser-pumped dye laser injection seeded by low-power He-Ne lasers

The design and operating characteristics of a dye laser pumped by a 3-W copper-vapor laser (CVL) and injection seeded by low-power (1-5 mW) He-Ne lasers at 633 nm are reported. An extremely simple optical arrangement is used wherein the output mirror of the He-Ne laser and a third mirror form the dye laser cavity. Laser efficiency in fixed-wavelength operation has been investigated for variable CVL pump power, He-Ne injection power and polarization, and cavity output coupling for a standard Rhodamine 590/Rhodamine 640 dye solution. Over 90% of free-running (unseeded) laser power is obtained in fixed-wavelength (seeded) operation at low CVL pump powers (≤1 W), dropping to approximately 60% at 3-W pump power. Maximum CVL pump to dye laser optical conversion efficiency in narrow-band, fixed-wavelength operation at 633 nm was 12%.