The electronic factor in Bergman cyclization

Through-bond interactions in 1,4-dehydrobenzene preferentially stabilize the out-of-phase combination of the radical hydrids, The resultant splitting between the frontier orbitals is crucial in making Bergman cyclization a symmetry-allowed process. Orbital symmetry also inhibits the radical centers from forming a C-C bond, enabling the biradical to survive as a local minimum capable of intermolecular hydrogen abstraction, Both these factors, which are important in the design of DNA cleaving molecules, are confirmed through calculations on biradicals formed from diynes in which through-bond interactions stabilize the in-phase combination of hybrids at the radical centers.

Experimental studies of lipped channel beams subject to web crippling under two-flange load cases

Lipped channel beams (LCBs) are commonly used as flexural members such as floor joists and bearers in the construction 6 industry. These thin-walled LCBs are subjected to specific buckling and failure modes, one of them being web crippling. Despite considerable 7 research in this area, some recent studies have shown that the current web crippling design rules are unable to predict the test capacities under 8 end-two-flange (ETF) and interior-two-flange (ITF) load conditions. In many instances, web crippling predictions by the available design 9 standards such as AISI S100, AS/NZS 4600 and Eurocode 3 Part 1-3 are inconsistent, i.e., unconservative in some cases, although they 10 are conservative in other cases. Hence, experimental studies consisting of 36 tests were conducted in this research to assess the web crippling 11 behavior and capacities of high-strength LCBs under two-flange load cases (ETF and ITF). Experimental results were then compared with the 12 predictions from current design rules. Comparison of the ultimate web crippling capacities from tests showed that the design equations are 13 very unconservative for LCB sections under the ETF load case and are conservative for the ITF load case. Hence, improved equations were 14 proposed to determine the web crippling capacities of LCBs based on the experimental results from this study. Current design equations do 15 not provide the direct strength method (DSM) provisions for web crippling. Hence, suitable design rules were also developed under the DSM 16 format using the test results and buckling analyses using finite-element analyses.

Experimental studies on web crippling strength of hollow flange channels under EOF and IOF load cases

LiteSteel beam (LSB) is a hollow flange channel made from cold-formed steel using a patented manufacturing process involving simultaneous cold-forming and dual electric resistance welding. LSBs are currently used as floor joists and bearers in buildings. However, there are no appropriate design standards available due to its unique hollow flange geometry, residual stress characteristics and initial geometric imperfections arising from manufacturing processes. Recent research studies have focused on investigating the structural behaviour of LSBs under pure bending, predominant shear and combined actions. However, web crippling behaviour and strengths of LSBs still need to be examined. Therefore, an experimental study was undertaken to investigate the web crippling behaviour and strengths of LSBs under EOF (End One Flange) and IOF (Interior One Flange) load cases. A total of 23 web crippling tests were performed and the results were compared with the current AS/NZS 4600 and AISI S100 design standards, which showed that the cold-formed steel design rules predicted the web crippling capacity of LSB sections very conservatively under EOF and IOF load cases. Therefore, suitably improved design equations were proposed to determine the web crippling capacity of LSBs based on experimental results. In addition, new design equations were also developed under the Direct Strength Method format. This paper presents the details of this experimental study on the web crippling behaviour and strengths of LiteSteel beams under EOF and IOF load cases and the results.

Web crippling tests of hollow flange channel beams with flanges fastened to supports under two flange load cases

Thin-walled steel hollow flange channel beams known as LiteSteel beam (LSB) sections were developed for use as joists and bearers in various flooring systems. However, they are subjected to specific buckling and failure modes, one of them being web crippling. Despite considerable research in this area, much of the current design predictions for cold-formed steel sections are not directly applicable to LSBs. This is due to the geometry of the LSB, which consists of two closed rectangular hollow flanges, and its unique residual stress characteristics and initial geometric imperfections. Hence an experimental study was conducted to investigate the web crippling behaviour and capacities of LSBs with their flanges fastened to supports. Thirty nine web crippling tests were conducted under two flange load cases (End Two Flange (ETF) and Interior Two Flange (ITF)). Test results showed that for ETF load case the web crippling capacities increased by 50% on average while they increased by 97% for ITF load case when flanges were fastened to supports. Comparison of the ultimate web crippling capacities from tests showed that AS/NZS 4600 and AISI S100 web crippling design equations are conservative for LSB sections with flanges fastened to supports under ETF and ITF load cases. Hence new equations were proposed to determine the web crippling capacities of LSBs with flanges fastened to supports. This paper presents the details of the experimental study into the web crippling behaviour of LSB sections with their flanges fastened under ETF and ITF load cases, and the results.

Experimental and numerical studies of hollow flange channel beams subject to web crippling under ETF and ITF load cases

This paper presents the details of experimental and numerical studies on the web crippling behaviour of hollow flange channel beams, known as LiteSteel beams (LSB). The LSB has a unique shape of a channel beam with two rectangular hollow flanges, made using a unique manufacturing process. Experimental and numerical studies have been carried out to evaluate the behaviour and design of LSBs subject to pure bending actions, predominant shear actions and combined actions. To date, however, no investigation has been conducted into the web crippling behaviour and strength of LSB sections under ETF and ITF load conditions. Hence experimental studies consisting of 28 tests were first conducted in this research to assess the web crippling behaviour and strengths of LSBs under two flange load cases (ETF and ITF). Experimental web crippling capacity results were then compared with the predictions from AS/NZS 4600 and AISI S100 design rules, which showed that AS/NZS 4600 and AISI S100 design equations are very unconservative for LSBs under ETF and ITF load cases. Hence improved equations were proposed to determine the web crippling capacities of LSBs. Finite element models of the tested LSBs were then developed, and used to determine the elastic buckling loads of LSBs under ETF and ITF load cases. New equations were proposed to determine the corresponding elastic buckling coefficients of LSBs. Finally suitable design rules were also developed under the Direct Strength Method format using the test results and buckling analysis results from finite element analyses.

Web crippling tests of rivet fastened rectangular hollow flange channel beams under two-flange load cases

The rivet-fastened rectangular hollow flange channel beam (RHFCB) is a new cold-formed hollow section proposed as an alternative to welded hollow flange steel beams. To date, no investigation has been conducted on their web crippling behaviour and strengths. Hence an experimental study was conducted to investigate the web crippling behaviour and capacities of rivet fastened RHFCBs under End Two Flange (ETF) and Interior Two Flange (ITF) load cases. Experimental results showed that the current design rules are unconservative for rivet fastened RHFCB sections under ETF and ITF load cases. Hence new equations were proposed to determine the web crippling capacities of rivet fastened RHFCBs.

System integration design in MEMS - A case study of micromachined load cell

One of the critical issues in large scale commercial exploitation of MEMS technology is its system integration. In MEMS, a system design approach requires integration of varied and disparate subsystems with one of a kind interface. The physical scales as well as the magnitude of signals of various subsystems vary widely. Known and proven integration techniques often lead to considerable loss in advantages the tiny MEMS sensors have to offer. Therefore, it becomes imperative to think of the entire system at the outset, at least in terms of the concept design. Such design entails various aspects of the system ranging from selection of material, transduction mechanism, structural configuration, interface electronics, and packaging. One way of handling this problem is the system-in-package approach that uses optimized technology for each function using the concurrent hybrid engineering approach. The main strength of this design approach is the fast time to prototype development. In the present work, we pursue this approach for a MEMS load cell to complete the process of system integration for high capacity load sensing. The system includes; a micromachined sensing gauge, interface electronics and a packaging module representing a system-in-package ready for end characterization. The various subsystems are presented in a modular stacked form using hybrid technologies. The micromachined sensing subsystem works on principles of piezo-resistive sensing and is fabricated using CMOS compatible processes. The structural configuration of the sensing layer is designed to reduce the offset, temperature drift, and residual stress effects of the piezo-resistive sensor. ANSYS simulations are carried out to study the effect of substrate coupling on sensor structure and its sensitivity. The load cell system has built-in electronics for signal conditioning, processing, and communication, taking into consideration the issues associated with resolution of minimum detectable signal. The packaged system represents a compact and low cost solution for high capacity load sensing in the category of compressive type load sensor.

Stress and developmental responses in Arabidopsis thaliana: regulation through the transcription factor-interacting protein RCD1

Plants constantly face adverse environmental conditions, such as drought or extreme temperatures that threaten their survival. They demonstrate astonishing metabolic flexibility in overcoming these challenges and one of the key responses to stresses is changes in gene expression leading to alterations in cellular functions. This is brought about by an intricate network of transcription factors and associated regulatory proteins. Protein-protein interactions and post-translational modifications are important steps in this control system along with carefully regulated degradation of signaling proteins. This work concentrates on the RADICAL-INDUCED CELL DEATH1 (RCD1) protein which is an important regulator of abiotic stress-related and developmental responses in Arabidopsis thaliana. Plants lacking this protein function display pleiotropic phenotypes including sensitivity to apoplastic reactive oxygen species (ROS) and salt, ultraviolet B (UV-B) and paraquat tolerance, early flowering and senescence. Additionally, the mutant plants overproduce nitric oxide, have alterations in their responses to several plant hormones and perturbations in gene expression profiles. The RCD1 gene is transcriptionally unresponsive to environmental signals and the regulation of the protein function is likely to happen post-translationally. RCD1 belongs to a small protein family and, together with its closest homolog SRO1, contains three distinguishable domains: In the N-terminus, there is a WWE domain followed by a poly(ADP-ribose) polymerase-like domain which, despite sequence conservation, does not seem to be functional. The C-terminus of RCD1 contains a novel domain called RST. It is present in RCD1-like proteins throughout the plant kingdom and is able to mediate physical interactions with multiple transcription factors. In conclusion, RCD1 is a key point of signal integration that links ROS-mediated cues to transcriptional regulation by yet unidentified means, which are likely to include post-translational mechanisms. The identification of RCD1-interacting transcription factors, most of whose functions are still unknown, opens new avenues for studies on plant stress as well as developmental responses.

Growth factor-loaded microparticles for tissue engineering: The discrepancies of in vitro characterization assays

Efficient and effective growth factor (GF) delivery is an ongoing challenge for tissue regeneration therapies. The accurate quantification of complex molecules such as GFs, encapsulated in polymeric delivery devices, is equally critical and just as complex as achieving efficient delivery of active GFs. In this study, GFs relevant to bone tissue formation, vascular endothelial growth factor (VEGF) and bone morphogenetic protein 7 (BMP-7), were encapsulated, using the technique of electrospraying, into poly(lactic-co-glycolic acid) microparticles that contained poly(ethylene glycol) and trehalose to assist GF bioactivity. Typical quantification procedures, such as extraction and release assays using saline buffer, generated a significant degree of GF interactions, which impaired accurate assessment by enzyme-linked immunosorbent assay (ELISA). When both dry BMP-7 and VEGF were processed with chloroform, as is the case during the electrospraying process, reduced concentrations of the GFs were detected by ELISA; however, the biological effect on myoblast cells (C2C12) or endothelial cells (HUVECs) was unaffected. When electrosprayed particles containing BMP-7 were cultured with preosteoblasts (MC3T3-E1), significant cell differentiation into osteoblasts was observed up to 3 weeks in culture, as assessed by measuring alkaline phosphatase. In conclusion, this study showed how electrosprayed microparticles ensured efficient delivery of fully active GFs relevant to bone tissue engineering. Critically, it also highlights major discrepancies in quantifying GFs in polymeric microparticle systems when comparing ELISA with cell-based assays.

The fully implicit stochastic-alpha method for stiff stochastic differential equations

A fully implicit integration method for stochastic differential equations with significant multiplicative noise and stiffness in both the drift and diffusion coefficients has been constructed, analyzed and illustrated with numerical examples in this work. The method has strong order 1.0 consistency and has user-selectable parameters that allow the user to expand the stability region of the method to cover almost the entire drift-diffusion stability plane. The large stability region enables the method to take computationally efficient time steps. A system of chemical Langevin equations simulated with the method illustrates its computational efficiency.

An FETI-preconditioned conjuerate gradient method for large-scale stochastic finite element problems

In the spectral stochastic finite element method for analyzing an uncertain system. the uncertainty is represented by a set of random variables, and a quantity of Interest such as the system response is considered as a function of these random variables Consequently, the underlying Galerkin projection yields a block system of deterministic equations where the blocks are sparse but coupled. The solution of this algebraic system of equations becomes rapidly challenging when the size of the physical system and/or the level of uncertainty is increased This paper addresses this challenge by presenting a preconditioned conjugate gradient method for such block systems where the preconditioning step is based on the dual-primal finite element tearing and interconnecting method equipped with a Krylov subspace reusage technique for accelerating the iterative solution of systems with multiple and repeated right-hand sides. Preliminary performance results on a Linux Cluster suggest that the proposed Solution method is numerically scalable and demonstrate its potential for making the uncertainty quantification Of realistic systems tractable.

Role of silicon in resisting subsurface plastic deformation in tribology of aluminium-silicon alloys

Silicon particles standing proud on aluminium-silicon alloy surfaces provide protection in tribology. Permanent sinking of such particles into the matrix under load can be deleterious. The mechanical response of the alloy to nano-indentation of single silicon particles embedded in the matrix is explored. A nominal critical pressure required to plastically deform the matrix to permanently embed the particle is determined experimentally. Within a framework suggested by two-dimensional models of plastic response to indentation, a probable correlation is established between the normal mean pressure required to cause permanent sinking of silicon particles and a factor which relates the relevant particle dimensions.

Death pathways activated in the neurotrophic factor-deprived neurons

Programed cell death (PCD) is a fundamental biological process that is as essential for the development and tissue homeostasis as cell proliferation, differentiation and adaptation. The main mode of PCD - apoptosis - occurs via specifi c pathways, such as mitochondrial or death receptor pathway. In the developing nervous system, programed death broadly occurs, mainly triggered by the defi ciency of different survival-promoting neurotrophic factors, but the respective death pathways are poorly studied. In one of the best-characterized models, sympathetic neurons deprived of nerve growth factor (NGF) die via the classical mitochondrial apoptotic pathway. The main aim of this study was to describe the death programs activated in these and other neuronal populations by using neuronal cultures deprived of other neurotrophic factors. First, this study showed that the cultured sympathetic neurons deprived of glial cell line-derived neurotrophic factor (GDNF) die via a novel non-classical death pathway, in which mitochondria and death receptors are not involved. Indeed, cytochrome c was not released into the cytosol, Bax, caspase-9, and caspase-3 were not involved, and Bcl-xL overexpression did not prevent the death. This pathway involved activation of mixed lineage kinases and c-jun, and crucially requires caspase-2 and -7. Second, it was shown that deprivation of neurotrophin-3 (NT-3) from cultured sensory neurons of the dorsal root ganglia kills them via a dependence receptor pathway, including cleavage of the NT- 3 receptor TrkC and liberation of a pro-apoptotic dependence domain. Indeed, death of NT-3-deprived neurons was blocked by a dominant-negative construct interfering with TrkC cleavage. Also, the uncleavable mutant of TrkC, replacing the siRNA-silenced endogeneous TrkC, was not able to trigger death upon NT-3 removal. Such a pathway was not activated in another subpopulation of sensory neurons deprived of NGF. Third, it was shown that cultured midbrain dopaminergic neurons deprived of GDNF or brainderived neurotrophic factor (BDNF) kills them by still a different pathway, in which death receptors and caspases, but not mitochondria, are activated. Indeed, cytochrome c was not released into the cytosol, Bax was not activated, and Bcl-xL did not block the death, but caspases were necessary for the death of these neurons. Blocking the components of the death receptor pathway - caspase-8, FADD, or Fas - blocked the death, whereas activation of Fas accelerated it. The activity of Fas in the dopaminergic neurons could be controlled by the apoptosis inhibitory molecule FAIML. For these studies we developed a novel assay to study apoptosis in the transfected dopaminergic neurons. Thus, a novel death pathway, characteristic for the dopaminergic neurons was described. The study suggests death receptors as possible targets for the treatment of Parkinson s disease, which is caused by the degeneration of dopaminergic neurons.