Ruthenium(II) bis(terpyridine) electron transfer complexes with alkynyl-ferrocenyl bridges: synthesis, structures, and electrochemical and spectroscopic studies

Two novel alkynyl-bridged symmetric bis-tridentate ligands 1,2-bis(1'-[4'-(2,2':6', 2 ''-terpyridinyl)]-ferrocenyl)ethyne (3a; tpy-Fc-C C-Fc-tpy; Fc = ferrocenyl; tpy = terpyridyl) and 1,4-bis(1'-[4'-(2,2':6', 2 ''-terpyridinyl)]ferrocenyl)-1,3-butadiyne (3b; tpy-Fc-C C-C C-Fc-tpy) and their Ru2+ complexes 6a and 6b have been synthesized and characterized by cyclic voltammetry, UV-vis and luminescence spectroscopy, and in the case of 3b by single-crystal X-ray diffraction. Cyclic voltammograms of both compounds, 3a and 3b, display two severely overlapping ferrocene-based oxidative peaks with only one reductive peak. The redox behavior of 6a and 6b is dominated by the Ru2+/Ru3+ redox couple (E-1/2 from 1.33 to 1.34 V), the Fe2+/Fe3+ redox couples (E-1/2 from 0.46 to 0.80 V), and the tpy/tpy(-)/tpy(2-)redox couples (E-1/2 from -1.19 to -1.48 V). The UV-vis spectra of 6a and 6b show absorption bands assigned to the (1)[(d(pi)(Fe))(6)] -> (1)[(d(pi)(Fe))(5)(pi*(Ru)(tpy))(1)] MMLCT transition at similar to 555 nm. Complexes 6a and 6b are luminescent in H2O-CH3CN (4 : 1, v/v) solution at room temperature, and 6b exhibits the strongest luminescence intensity (lambda(em)(max): 710 nm, Phi(em): 2.28 x 10(-4), tau: 358 ns) relative to analogous ferrocene-based bis(terpyridine) Ru(II) complexes reported so far.

Kruppel-associated Box (KRAB)-associated co-repressor (KAP-1) Ser-473 phosphorylation regulates heterochromatin protein 1β (HP1-β) mobilization and DNA repair in heterochromatin

The DNA damage response encompasses a complex series of signaling pathways that function to regulate and facilitate the repair of damaged DNA. Recent studies have shown that the repair of transcriptionally inactive chromatin, named heterochromatin, is dependent upon the phosphorylation of the co-repressor, Krüppel-associated box (KRAB) domain-associated protein (KAP-1), by the ataxia telangiectasia-mutated (ATM) kinase. Co-repressors, such as KAP-1, function to regulate the rigid structure of heterochromatin by recruiting histone-modifying enzymes, such HDAC1/2, SETDB1, and nucleosome-remodeling complexes such as CHD3. Here, we have characterized a phosphorylation site in the HP1-binding domain of KAP-1, Ser-473, which is phosphorylated by the cell cycle checkpoint kinase Chk2. Expression of a nonphosphorylatable S473A mutant conferred cellular sensitivity to DNA-damaging agents and led to defective repair of DNA double-strand breaks in heterochromatin. In addition, cells expressing S473A also displayed defective mobilization of the HP1-ß chromodomain protein. The DNA repair defect observed in cells expressing S473A was alleviated by depletion of HP1-ß, suggesting that phosphorylation of KAP-1 on Ser-473 promotes the mobilization of HP1-ß from heterochromatin and subsequent DNA repair. These results suggest a novel mechanism of KAP-1-mediated chromatin restructuring via Chk2-regulated HP1-ß exchange from heterochromatin, promoting DNA repair.

Commissioning and Evaluation of a Fiber-Optic Sensor System for Bridge Monitoring

This paper describes the design, commissioning, and evaluation of a ?ber-optic strain sensor system for the structural health monitoring of a prestressed concrete posttensioned box girder railway bridge in Mumbai, India, which shows a number of well-documented structural problems. Preliminary laboratory trials to design the most appropriate sensor system that could be readily transported and used on site are described, followed by a description of load tests on the actual bridge undertaken in collaboration with Indian Railways and using locomotives of known weight. Results from the load tests using the optical system are compared with similar results obtained using electrical resistance strain gages. Conclusions are summarized concerning the integrity of the structure and for the future use of the sensor system for monitoring bridges of this type. Crack width measurements obtained during the load tests are also described.

Scalable black-box prediction models for multi-dimensional adaptation on NUMA multi-cores

This paper presents a scalable, statistical ‘black-box’ model for predicting the performance of parallel programs on multi-core non-uniform memory access (NUMA) systems. We derive a model with low overhead, by reducing data collection and model training time. The model can accurately predict the behaviour of parallel applications in response to changes in their concurrency, thread layout on NUMA nodes, and core voltage and frequency. We present a framework that applies the model to achieve significant energy and energy-delay-square (ED2) savings (9% and 25%, respectively) along with performance improvement (10% mean) on an actual 16-core NUMA system running realistic application workloads. Our prediction model proves substantially more accurate than previous efforts.

Structural damage diagnosis of steel truss bridges by outlier detection

This study discusses structural damage diagnosis of real steel truss bridges by measuring trafficinduced vibration of bridges and utilizing a damage indicator derived from linear system parameters of a time series model. On-site damage experiments were carried out on real steel truss bridges. Artificial damage was applied to the bridge by severing a truss member with a cutting machine.Vehicle-induced vibrations of the bridges before and after applying damagewere measured and used in structural damage diagnosis of the bridges. Changes in the damage indicator are detected by Mahalanobis-Taguchi system (MTS) which is one of multivariate outlier analyses. The damage indicator and outlier detection was successfully applied to detect anomalies in the steel truss bridges utilizing vehicle-induced vibrations. Observations through this study demonstrate feasibility of the proposed approach for real world applications.

Unspliced X-box-binding Protein 1 (XBP1) Protects Endothelial Cells from Oxidative Stress through Interaction with Histone Deacetylase 3

It is well-known that atherosclerosis occurs geographically at branch points where disturbed flow predisposes to the development of plaque via triggering of oxidative stress and inflammatory reactions. In this study, we found that disturbed flow activated anti-oxidative reactions via up-regulating heme oxygenase 1 (HO-1) in an X-box binding protein 1 (XBP1) and histone deacetylase 3 (HDAC3)-dependent manner. Disturbed flow concomitantly up-regulated the unspliced XBP1 (XBP1u) and HDAC3 in a vascular endothelial growth factor receptor (VEGFR) and PI3K/Akt dependent manner. The presence of XBP1 was essential for the up-regulation of HDAC3 protein. Over-expression of XBP1u and/or HDAC3 activated Akt1 phosphorylation, Nrf2 protein stabilization and nuclear translocation, and HO-1 expression. Knockdown of XBP1u decreased the basal level and disturbed flow-induced Akt1 phosphorylation, Nrf2 stabilization and HO-1 expression. Knockdown of HDAC3 ablated XBP1u-mediated effects. The mammalian target of rapamycin complex 2 (mTORC2) inhibitor, AZD2014, ablated XBP1u or HDAC3 or disturbed flow-mediated Akt1 phosphorylation, Nrf2 nuclear translocation and HO-1 expression. Neither actinomycin D nor cycloheximide affected disturbed flow-induced up-regulation of Nrf2 Protein. Knockdown of Nrf2 abolished XBP1u or HDAC3 or disturbed flow-induced HO-1 up-regulation. Co-immunoprecipitation assays demonstrated that XBP1u physically bound to HDAC3 and Akt1. The region of amino acids 201 to 323 of the HDAC3 protein was responsible for the binding to XBP1u. Double immunofluorescence staining revealed that the interactions between Akt1 and mTORC2, Akt1 and HDAC3, Akt1 and XBP1u, HDAC3 and XBP1u occurred in the cytosol. Thus, we demonstrate that XBP1u and HDAC3 exert a protective effect on disturbed flow-induced oxidative stress via up-regulation of mTORC2-dependent Akt1 phosphorylation and Nrf2-mediated HO-1 expression.

Containing the Nanometer "Pandora-Box": Cross-Layer Design Techniques for Variation Aware Low Power Systems

The demand for richer multimedia services, multifunctional portable devices and high data rates can only been visioned due to the improvement in semiconductor technology. Unfortunately, sub-90 nm process nodes uncover the nanometer Pandora-box exposing the barriers of technology scaling-parameter variations, that threaten the correct operation of circuits, and increased energy consumption, that limits the operational lifetime of today's systems. The contradictory design requirements for low-power and system robustness, is one of the most challenging design problems of today. The design efforts are further complicated due to the heterogeneous types of designs ( logic, memory, mixed-signal) that are included in today's complex systems and are characterized by different design requirements. This paper presents an overview of techniques at various levels of design abstraction that lead to low power and variation aware logic, memory and mixed-signal circuits and can potentially assist in meeting the strict power budgets and yield/quality requirements of future systems.

The hydraulics and resulting bed scour within the vicinity of Submerged Single Span Arch Bridges

As a consequence of climate change there is now a more frequent occurrence of extreme rainfall events where, with higher rates of urbanisation, the built environment has become increasingly affected by flooding.. This is of particular importance in relation to the stability of bridge structures that span rivers and canals etc. In November 2009, the UK and Ireland were subjected to extraordinarily severe weather conditions for several days. The rainfall was logged as the highest level of rainfall ever recorded within the UK, and as a direct consequence, unprecedented flooding occurred in Cumbria. This flooding led to the collapse of three road bridges which were generally 19th century masonry arch bridges, with relatively shallow foundations. In the UK, knowledge of the combined effect of bridge scouring and inundation has been not been particularly widely studied. Research carried out by Hamill et al [1] considered the hydraulic analysis of single arch bridges under flood conditions, but no consideration was given towards the likely damage to these structures due to scouring. Prior to this, Bierry and Delleur [2] produced a classic paper in predicting the discharge downstream of an inundated arch, focussing on predicting afflux as opposed to bridge scour. Further work on backwater effects was carried out by Martin-Vide & Prio [3] in semi-circular arch bridges. Both pressurized and free-surface flows at the bridge were investigated. Flows on a mobile bed in clear-water conditions were compared to those with a rigid bed, but no predictive equation for scour under pressurised conditions was considered. This paper will present initial findings from an experimental investigation into the effects of surcharged flow and subsequent scour within the vicinity of single span arch bridges. Velocities profiles will be shown within the vicinity of the arch, in addition to the depth of clear water scour, for a series of flows and model spans. The data will be presented, where results will be correlated to the most recent predictive equations that are proposed.

DEAD-box helicase DP103 defines metastatic potential of human breast cancers

Despite advancement in breast cancer treatment, 30% of patients with early breast cancers experience relapse with distant metastasis. It is a challenge to identify patients at risk for relapse; therefore, the identification of markers and therapeutic targets for metastatic breast cancers is imperative. Here, we identified DP103 as a biomarker and metastasis-driving oncogene in human breast cancers and determined that DP103 elevates matrix metallopeptidase 9 (MMP9) levels, which are associated with metastasis and invasion through activation of NF-κB. In turn, NF-κB signaling positively activated DP103 expression. Furthermore, DP103 enhanced TGF-β-activated kinase-1 (TAK1) phosphorylation of NF-κB-activating IκB kinase 2 (IKK2), leading to increased NF-κB activity. Reduction of DP103 expression in invasive breast cancer cells reduced phosphorylation of IKK2, abrogated NF-κB-mediated MMP9 expression, and impeded metastasis in a murine xenograft model. In breast cancer patient tissues, elevated levels of DP103 correlated with enhanced MMP9, reduced overall survival, and reduced survival after relapse. Together, these data indicate that a positive DP103/NF-κB feedback loop promotes constitutive NF-κB activation in invasive breast cancers and activation of this pathway is linked to cancer progression and the acquisition of chemotherapy resistance. Furthermore, our results suggest that DP103 has potential as a therapeutic target for breast cancer treatment.