Alteration of the Route to Menaquinone towards Isochorismate-Derived Metabolites

Chorismate and isochorismate constitute branch-point intermediates in the biosynthesis of many aromatic metabolites in microorganisms and plants. To obtain unnatural compounds, we modified the route to menaquinone in Escherichia coli. We propose a model for the binding of isochorismate to the active site of MenD ((1R,2S, 5S,6S)-2-succinyl-5-enolpyruvyl-6-hydroxycyclohex-3-ene-1-carboxylate (SEPHCHC) synthase) that explains the outcome of the native reaction with α-ketoglutarate. We have rationally designed variants of MenD for the conversion of several isochorismate analogues. The double-variant Asn117Arg–Leu478Thr preferentially converts (5S,6S)-5,6-dihydroxycyclohexa-1,3-diene-1-carboxylate (2,3-trans-CHD), the hydrolysis product of isochorismate, with a >70-fold higher ratio than that for the wild type. The single-variant Arg107Ile uses (5S,6S)-6-amino-5-hydroxycyclohexa-1,3-diene-1-carboxylate (2,3-trans-CHA) as substrate with >6-fold conversion compared to wild-type MenD. The novel compounds have been made accessible in vivo (up to 5.3 g L⁻¹). Unexpectedly, as the identified residues such as Arg107 are highly conserved (>94 %), some of the designed variations can be found in wild-type SEPHCHC synthases from other bacteria (Arg107Lys, 0.3 %). This raises the question for the possible natural occurrence of as yet unexplored branches of the shikimate pathway.     

Scaling planar silicon devices

The generation-over-generation scaling of critical CMOS technology parameters is ultimately bound by nonscalable limitations, such as the thermal voltage and the elementary electronic charge. Sustained improvement in performance and density has required the introduction of new device structures and materials. Partially depleted SOI, a most recent MOSFET innovation, has extended VLSI performance while introducing unique idiosyncrasies. Fully depleted SOI is one logical extension of this device design direction. Gate dielectric tunneling, device self-heating, and single-event upsets present developers of these next-generation devices with new challenges. Strained silicon and high-permittivity gate dielectric are examples of new materials that will enable CMOS developers to continue to deliver device performance enhancements in the sub-100 nm regime.     

混合信号芯片设计处理关键的转折阶段

通过简单地剪切和粘贴知识产权(IP)内核可以加快无工厂半导体公司的系统级芯片(SOC)设计。 过去十年中,涌现出大量的为系统制造商提供专用芯片(ASIC)的小型IC设计公司。这些被称为无工厂企业(因为他们将IC制造过程转交给商业芯片制造工厂),需要的启动资金较少,而且如果市场接受他们的产品的话,能够获得丰厚的回报。在大量设计工具的支持下,这些无工厂设计企业在历史悠久的大型芯片制造商,如IBM、Intel、Motorola和德州仪器公司所主导的市场中赢得了一席之地。     

A three-phase model for mixed columnar-equiaxed solidification

A three-phase model for mixed columnar-equiaxed solidification is presented in this article. The three phases are the parent melt as the primary phase, as well as the solidifying columnar dendrites and globular equiaxed grains as two different secondary phases. With an Eulerian approach, the three phases are considered as spatially coupled and interpenetrating continua. The conservation equations of mass, momentum, species, and enthalpy are solved for all three phases. An additional conservation equation for the number density of the equiaxed grains is defined and solved. Nucleation of the equiaxed grains, diffusion-controlled growth of both columnar and equiaxed phases, interphase exchanges, and interactions such as mass transfer during solidification, drag force, solute partitioning at the liquid/solid interface, and release of latent heat are taken into account. Binary steel ingots (Fe-0.34 wt pct C) with two-dimensional (2-D) axis symmetrical and three-dimensional (3-D) geometries as a benchmark were simulated. It is demonstrated that the model can be used to simulate the mixed columnar-equiaxed solidification, including melt convection and grain sedimentation, macrosegregation, columnar-to-equiaxed-transition (CET), and macrostructure distribution. The model was evaluated by comparing it to classical analytical models based on limited one-dimensional (1-D) cases. Satisfactory results were obtained. It is also shown that in order to apply this model for industrial castings, further improvements are still necessary concerning some details.     

Dynamics of Interacting OH– and OD– Ions in KCl

OH^– and OD^– defects are known to form rotational tunneling systems in KCl host crystals. We have studied the complex dielectric susceptibility of KCl doped with different concentrations of OH^– and OD^– in a wide range of frequencies and temperatures. Our main result is that there is a transition from coherent single ion tunneling at low defect concentration to an incoherent tunneling motion at high defect concentrations. In addition, we have studied the thermally activated motion of pairwise coupled hydroxide ions in an attempt to obtain information on the microscopic configurations of the different pairs contributing to the dielectric loss. PACS numbers: 61.72.Ji, 77.22-d, 78.30.Ly     

Synthesis of Aminopyridazines from Aminocyclopropenylium Salts and Diazomethyl Compounds [1]

Amino-substituted cyclopropenylium salts ( 11a,b ) react with diazomethyl compounds ( 12a-i ) in dichloromethane or acetonitrile in the presence of a base (ethyldiisopropylamine, 1,5-diazabicyclo[4.3.0] non-5-ene) to form 4-aminopyridazines ( 13a-i ) specifically. The reaction is interpreted in terms of an initial electrophilic diazoalkane substitution to give diazomethylcyclopropenes ( 11 + 12 → 14 ) which undergo a [1.5]-cyclisation to form the betaines 16 which, in turn, isomerise with opening of the bridging bond to give the aminopyridazines 13 . In a similar manner, the tris[amino] cyclopropenylium salts 8a,b and 10a-c are converted to the 3,4,5-tris[amino]-pyridazines ( 21a-k ) by treatment with diazomethyl compounds ( 12a, c-f ).     

Isolation and Spectroscopic Characterization of Eu@C72

A new Eu-endohedral fullerene cage, namely, Eu@C₇₂, was synthesized, separated, and a single isomer, Eu@C₇₂-I, has been isolated by multi-step HPLC for the first time and characterized by LDI-TOF mass spectrometry, UV-Vis and EPR spectroscopy. Additionally, a second isomer, Eu@C₇₂-II, has been separated by HPLC and identified by LDI-TOF mass spectrometry.     

A Profile of Psychologists' Views of Critical Risk Factors for Completed Suicide in Older Adults.

The ability to accurately and reliably predict whether an older adult will commit suicide has eluded clinicians and researchers. A random national sample of psychologists who work with older adults was surveyed regarding their perception of 36 risk factors for completed suicide and indirect self-destructive behavior in older adults. This study produced a profile of psychologists' assessment and treatment practices when working with suicidal older adults. Determining what psychologists consider to be the most salient risk factors for completed suicide is important in identifying a minimum standard that clinicians should follow when assessing older adults. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Low-power digital filtering using approximate processing

We present an algorithmic approach to the design of low-power frequency-selective digital filters based on the concepts of adaptive filtering and approximate processing. The proposed approach uses a feedback mechanism in conjunction with well-known implementation structures for finite impulse response (FIR) and infinite impulse response (IIR) digital filters. Our algorithm is designed to reduce the total switched capacitance by dynamically varying the filter order based on signal statistics. A factor of 10 reduction in power consumption over fixed-order filters is demonstrated for the filtering of speech signals     

Introduction to the special series: HIV infection among drug abusers.

Drug users are particularly at risk for contracting the human immunodeficiency virus and serve as a major mechanism for spreading the virus to other sectors of the population. As a result drug abuse treatment and potential behavioral change strategies are primary public health issues. The purpose of this article is to review the contributions included in this special edition, which represent an effort to describe the most current thinking in the field with a blend of theoretical, review, and empirical articles. (PsycINFO Database Record (c) 2010 APA, all rights reserved)