High-yield bacterial expression and structural characterization of recombinant human insulin-like growth factor binding protein-2

The diverse biological activities of the insulin-like growth factors (IGF-1 and IGF-2) are mediated by the IGF-1 receptor (IGF-1R). These actions are modulated by a family of six IGF-binding proteins (ICFBP-1-6; 22-31 kDa) that via high affinity binding to the IGFs (K-D similar to 300-700 pM) both protect the IGFs in the circulation and attenuate IGF action by blocking their receptor access In recent years, IGFBPs have been implicated in a variety of cancers However, the structural basis of their interaction with IGFs and/or other proteins is not completely understood A critical challenge in the structural characterization of full-length IGFBPs has been the difficulty in expressing these proteins at levels suitable for NMR/X-ray crystallography analysis Here we describe the high-yield expression of full-length recombinant human IGFBP-2 (rhIGFBP-2) in Eschericha coli Using a single step purification protocol, rhIGFBP-2 was obtained with >95% purity and structurally characterized using NMR spectroscopy. The protein was found to exist as a monomer at the high concentrations required for structural studies and to exist in a single conformation exhibiting a unique intra-molecular disulfide-bonding pattern The protein retained full biologic activity. This study represents the first high-yield expression of wild-type recombinant human IGFBP-2 in E coli and first structural characterization of a full-length IGFBP (C) 2010 Elsevier Inc. All rights reserved

Spinodal decomposition of a Co-Ti-Nb alloy

The microstructural evolution on aging a Co-3 wt pct Ti-2 wt pct Nb alloy has been followed by transmission electron microscopy and diffraction to show that the solid solution decomposed by the spinodal mode. The strengthening observed has been correlated with the differences in lattice parameters of the coexisting phases. The several stages of coarsening have been documented to yield information about their kinetics and morphological changes.Formerly Visiting Assistant Professor, Department of Mechanical and Industrial Engineering, University of Illinois at Urbana-Champaign, 1206 West Green Street, Urbana, IL 61801, is with .

A novel supersecondary structure in globular proteins comprising the collagen-like helix and ?-turn

A structure consisting of the polyproline-II or collagen-like helix immediately succeeded by a ?-turn is seen in several synthetic peptides and has been suggested to be the conformational requirement for proline hydroxylation in nascent procollagen. Using a simple algorithm for detecting secondary structures, we have analysed crystal structure data on 40 globular proteins and have found eight examples of the collagen-helix + ?-turn supersecondary structure in 15 proteins that contain the collagen-like helical segments.

Self-assembled flower-like nanostructures of InN and GaN grown by plasma-assisted molecular beam epitaxy

Nanosized hexagonal InN flower-like structures were fabricated by droplet epitaxy on GaN/Si(111) and GaN flower-like nanostructure fabricated directly on Si(111) substrate using radio frequency plasma-assisted molecular beam epitaxy. Powder X-ray diffraction (XRD) and scanning electron microscopy (SEM) were used to study the crystallinity and morphology of the nanostructures. Moreover, X-ray photoelectron spectroscopy (XPS) and photoluminescence (PL) were used to investigate the chemical compositions and optical properties of nano-flowers, respectively. Activation energy of free exciton transitions in GaN nano-flowers was derived to be similar to 28.5 meV from the temperature dependent PL studies. The formation process of nano-flowers is investigated and a qualitative mechanism is proposed.

Defining the pathway to insulin-like growth factor system targeting in cancer

The insulin-like growth factors (IGEs; IGF-1 and IGF-2) play central roles in cell growth, differentiation, survival, transformation and metastasis. The biologic effects of the IGFs are mediated by the IGF-1 receptor (IGF-1R), a receptor tyrosine kinase with homology to the insulin receptor (IR). Dysregulation of the ICE system is well recognized as a key contributor to the progression of multiple cancers, with IGF-1R activation increasing the tumorigenic potential of breast, prostate, lung, colon and head and neck squamous cell carcinoma (HNSCC). Despite this relationship, targeting the IGF-1R has only recently undergone development as a molecular cancer therapeutic. As it has taken hold, we are witnessing a robust increase and interest in targeting the inhibition of IGF-1R signaling. This is accentuated by the list of over 30 drugs, including monoclonal antibodies (mAbs) and tyrosine kinase inhibitors (TKIs) that are under evaluation as single agents or in combination therapies 1]. The ICE-binding proteins (IGFBPs) represent the third component of the ICE system consisting of a class of six soluble secretory proteins. They represent a unique class of naturally occurring ICE-antagonists that bind to and sequester IGF-1 and IGF-2, inhibiting their access to the IGF-1R. Due to their dual targeting of the IGFs without affecting insulin action, the IGFBPs are an untapped ``third'' class of IGF-1R inhibitors. in this commentary, we highlight some of the significant aspects of and prospects for targeting the IGF-1R and describe what the future may hold. (C) 2010 Elsevier Inc. All rights reserved.

High-Temperature (1023 K to 1273 K 750 degrees C to 1000 degrees C]) Plastic Deformation Behavior of B-Modified Ti-6Al-4V Alloys: Temperature and Strain Rate Effects

A minor addition of B to the Ti-6Al-4V alloy, by similar to 0.1 wt pct, reduces its as-cast prior beta grain size by an order of magnitude, whereas higher B content leads to the presence of in situ formed TiB needles in significant amounts. An experimental investigation into the role played by these microstructural modifications on the high-temperature deformation behavior of Ti-6Al-4V-xB alloys, with x varying between 0 wt pct and 0.55 wt pct, was conducted. Uniaxial compression tests were performed in the temperature range of 1023 K to 1273 K (750 degrees C to 1000 degrees C) and in the strain rate range of 10(-3) to 10(+1) s(-1). True stress-true strain responses of all alloys exhibit flow softening at lower strain rates and oscillations at higher strain rates. The flow softening is aided by the occurrence of dynamic recrystallization through lath globularization in high temperature (1173 K to 1273 K 900 degrees C to 1000 degrees C]) and a lower strain rate (10(-2) to 10(-3) s(-1)) regime. The grain size refinement with the B addition to Ti64, despite being marked, had no significant effect on this. Oscillations in the flow curve at a higher strain rate (10(0) to 10(+1) s(-1)), however, are associated with microstructural instabilities such as bending of laths, breaking of lath boundaries, generation of cavities, and breakage of TiB needles. The presence of TiB needles affected the instability regime. Microstructural evidence suggests that the matrix cavitation is aided by the easy fracture of TiB needles.

Interdiffusion studies in bulk Au-Ti system

The performance of the contacts, where Au/Ti layers are used in the metallization scheme, largely depends on the product phases grown by interdiffusion at the interface. It is found that four intermetallic compounds grow with narrow homogeneity range and wavy interfaces in the interdiffusion zone. The presence of wavy interfaces is the indication of high anisotropy in diffusion of the product phases. This also reflects in the deviation of parabolic growth from the average. Further, we have determined the relevant diffusion parameters, such as interdiffusion coefficient in the penetrated region of the end members and integrated diffusion coefficients of the intermetallic compounds.

Comparative study of adaptive frequency hopping with power control to avoid WLAN interference in WPAN systems like Bluetooth

Presently Bluetooth(BT) is one of the widely used device for personal communication. As BT devices are operating in the unlicensed ISM band, they are often subjected to the interference from WLAN. The band width of BT (1MHz) is narrower compare to the bandwidth of WLAN (22MHz). So for coexistence purpose it is important to observe the performance of narrow band signal BT in presence of wideband interference WLAN and vice versa. As there are many work on the performance of WLAN in presence BT interference 3]4]5]6], the main focus in this paper is on performance of BT in presence of WLAN interference in AWGN, Rayleigh fading channel. Then comparison of the performance using interference avoidance technique like adaptive frequency hopping, power control for BT system is given. Finally a conclusion is drawn observing the simulation results on the technique which is more suitable for WLAN interference mitigation in BT system.

Effects of Zr and Ti doping on the dielectric response of CeO2: A comparative first-principles study

Zr doping in ceria (CeO2) results in enhanced static dielectric response compared to pure ceria. On the other hand, Ti doping in ceria keeps its dielectric constant unchanged. We use first-principles density functional theory calculations based on pseudopotentials and a plane wave basis to determine electronic properties and dielectric response of Zr/Ti-doped and oxygen-vacancy-introduced ceria. Softening of phonon modes is responsible for the enhancement in dielectric response of Zr-doped ceria compared to that of pure ceria. The ceria-zirconia mixed oxides should have potential use as high-k materials in the semiconductor industry. (c) 2010 Elsevier Ltd. All rights reserved.

Importance of meridional circulation i flux transport dynamo: the possibility of a maunder-like grand minimum

Meridional circulation is an important ingredient in flux transport dynamo models. We have studied its importance on the period, the amplitude of the solar cycle, and also in producing Maunder-like grand minima in these models. First, we model the periods of the last 23 sunspot cycles by varying the meridional circulation speed. If the dynamo is in a diffusion-dominated regime, then we find that most of the cycle amplitudes also get modeled up to some extent when we model the periods. Next, we propose that at the beginning of the Maunder minimum the amplitude of meridional circulation dropped to a low value and then after a few years it increased again. Several independent studies also favor this assumption. With this assumption, a diffusion-dominated dynamo is able to reproduce many important features of the Maunder minimum remarkably well. If the dynamo is in a diffusion-dominated regime, then a slower meridional circulation means that the poloidal field gets more time to diffuse during its transport through the convection zone, making the dynamo weaker. This consequence helps to model both the cycle amplitudes and the Maunder-like minima. We, however, fail to reproduce these results if the dynamo is in an advection-dominated regime.

Enhancement of fatigue life of Ni-Ti-Fe shape memory alloys by thermal cycling

The effect of thermal cycling on the load-controlled tension-tension fatigue behavior of a Ni-Ti-Fe shape memory alloy (SMA) at room temperature was studied. Considerable strain accumulation was observed to occur in this alloy under both quasi-static and cyclic loading conditions. Though, in all cases, steady-state is reached within the first 50-100 cycles, the accumulated steady-state strain, epsilon(p.ss), is much smaller in thermally cycled alloy. As a result, the fatigue performance of them was found to be significantly enhanced vis-a-vis the as-solutionized alloy. Furthermore, under load-controlled conditions, the fatigue life of Ni-Ti-Fe alloys was found to be exclusively dependent on epsilon(p.ss). Observations made by profilometry and differential scanning calorimetry (DSC) indicate that the 200-500% enhancement in fatigue life of thermally cycled alloy is due to the homogeneous distribution of the accumulated fatigue strain. (C) 2010 Elsevier B.V. All rights reserved.

On characterization of deformation microstructure in Boron modified Ti-6Al-4V alloy

Addition of boron in small quantities to various titanium alloys have shown significant improvement in mechanical behavior of materials. In the present study, electron back-scatter diffraction (EBSD) techniques have been applied to investigate the deformation microstructure evolution in boron modified two-phase titanium alloy Ti-6Al-4V. The alloy was hot compressed at 750 degrees C up to 50% height reduction at two different strain rates (10(-3) s(-1) and 1 s(-1)). The EBSD analyses indicated significant differences in deformed microstructure of the base alloy and the alloy containing boron. A strong subgrain formation tendency was observed along with inhomogeneous distribution of dislocations inside large a colonies of Ti64. In contrast, a colonies were relatively strain free for Ti64 + B, with more uniform dislocation density distribution. The observed difference is attributed to microstructural modifications viz, grain size refinement and presence of TiB particles at grain boundary produced due to boron addition. (C) 2010 Elsevier B.V. All rights reserved.

Fatigue in Ti-6Al-4V-B alloys

The addition of small amounts of B to Ti-6Al-4V alloy reduces the as-cast grain size by an order of magnitude and introduces TiB phase into the microstructure. The effects of these microstructural modifications on both the high cycle fatigue and cyclic stress-strain response were investigated. Experimental results show that B addition markedly enhances the fatigue strength of the alloy; however, the influence of prior-beta grain size was found to be only marginal. The presence of TiB particles in the matrix appears to be beneficial with the addition of 0.55 wt.% B to Ti-6Al-4V enhancing the fatigue strength by more than 50%. Strain-controlled fatigue experiments reveal softening in the cyclic stress-strain response, which increases with the B content in the alloy. Transmission electron microscopy of the fatigued specimens indicates that generation of dislocations during cyclic loading and creation of twins due to strain incompatibility between the matrix and the TiB phase are possible reasons for the observed softening. (c) 2010 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

A functional style of programming with CSP-like communication mechanisms

This paper introduces CSP-like communication mechanisms into Backus’ Functional Programming (FP) systems extended by nondeterministic constructs. Several new functionals are used to describe nondeterminism and communication in programs. The functionals union and restriction are introduced into FP systems to develop a simple algebra of programs with nondeterminism. The behaviour of other functionals proposed in this paper are characterized by the properties of union and restriction. The axiomatic semantics of communication constructs are presented. Examples show that it is possible to reason about a communicating program by first transforming it into a non-communicating program by using the axioms of communication, and then reasoning about the resulting non-communicating version of the program. It is also shown that communicating programs can be developed from non-communicating programs given as specifications by using a transformational approach.