Correlations between designability and various structural characteristics of protein lattice models

Using six kinds of lattice types (4×4 ,5×5 , and6×6 square lattices;3×3×3 cubic lattice; and2+3+4+3+2 and4+5+6+5+4 triangular lattices), three different size alphabets (HP ,HNUP , and 20 letters), and two energy functions, the designability of proteinstructures is calculated based on random samplings of structures and common biased sampling (CBS) of proteinsequence space. Then three quantities stability (average energy gap),foldability, and partnum of the structure, which are defined to elucidate the designability, are calculated. The authors find that whatever the type of lattice, alphabet size, and energy function used, there will be an emergence of highly designable (preferred) structure. For all cases considered, the local interactions reduce degeneracy and make the designability higher. The designability is sensitive to the lattice type, alphabet size, energy function, and sampling method of the sequence space. Compared with the random sampling method, both the CBS and the Metropolis Monte Carlo sampling methods make the designability higher. The correlation coefficients between the designability, stability, and foldability are mostly larger than 0.5, which demonstrate that they have strong correlation relationship. But the correlation relationship between the designability and the partnum is not so strong because the partnum is independent of the energy. The results are useful in practical use of the designability principle, such as to predict the proteintertiary structure.

Expression of PSA-RP2, an alternatively spliced variant from the PSA gene, is increased in prostate cancer tissues but the protein is not secreted from prostate cancer cells

PSA-RP2 is a variant transcript expressed from the PSA gene that is conserved in gorillas, chimpanzees and humans suggesting a particular relevance for this transcript in these primates. We demonstrated by qRT-PCR that PSA-RP2 is upregulated in prostate cancer compared with benign prostatic hyperplasia tissues. The PSA-RP2 protein was not detected in seminal fluid and was cytoplasmically localised but not secreted from LNCaP or transfected PC3 prostate cells, despite secretion from transfected Cos-7 and HEK293 kidney cell lines. PSA-RP2-transfected PC3 cells showed slightly decreased proliferation and increased migration towards PC3-conditioned medium that could suggest a functional role in prostate cancer.

Mechanical properties of cold-formed steels at elevated temperatures

Mechanical properties have an important role in the fire safety design of cold-formed steel structures due to the rapid reduction in mechanical properties such as yield strength and elastic modulus under fire conditions and associated reduction to the load carrying capacities. Hence there is a need to fully understand the deterioration characteristics of yield strength and elastic modulus of cold-formed steels at elevated temperatures. Although past research has produced useful experimental data on the mechanical properties of cold-formed steels at elevated temperatures, such data do not yet cover different cold-formed steel grades and thicknesses. Therefore, an experimental study was undertaken to investigate the elevated temperature mechanical properties of two low and high strength steels with two thicknesses that are commonly used in Australia. Tensile coupon tests were undertaken using a steady state test method for temperatures in the range 20–700 °C. Test results were compared with the currently available reduction factors for yield strength and elastic modulus, and stress–strain curves, based on which further improvements were made. For this purpose, test results of many other cold-formed steels were also used based on other similar studies undertaken at the Queensland University of Technology. Improved equations were developed to predict the yield strength and elastic modulus reduction factors and stress–strain curves of a range of cold-formed steel grades and thicknesses used in Australia. This paper presents the results of this experimental study, comparisons with the results of past research and steel design standards, and the new predictive equations.

Numerical modelling of light gauge cold-formed steel compression members subjected to distortional buckling at elevated temperatures

Fire safety design of building structures has received greater attention in recent times due to continuing loss of properties and lives during fires. However, fire performance of light gauge cold-formed steel structures is not well understood despite its increased usage in buildings. Cold-formed steel compression members are susceptible to various buckling modes such as local and distortional buckling and their ultimate strength behaviour is governed by these buckling modes. Therefore a research project based on experimental and numerical studies was undertaken to investigate the distortional buckling behaviour of light gauge cold-formed steel compression members under simulated fire conditions. Lipped channel sections with and without additional lips were selected with three thicknesses of 0.6, 0.8, and 0.95 mm and both low and high strength steels (G250 and G550 steels). More than 150 compression tests were undertaken first at ambient and elevated temperatures. Finite element models of the tested compression members were then developed by including the degradation of mechanical properties with increasing temperatures. Comparison of finite element analysis and experimental results showed that the developed finite element models were capable of simulating the distortional buckling and strength behaviour at ambient and elevated temperatures up to 800 °C. The validated model was used to determine the effects of mechanical properties, geometric imperfections and residual stresses on the distortional buckling behaviour and strength of cold-formed steel columns. This paper presents the details of the numerical study and the results. It demonstrated the importance of using accurate mechanical properties at elevated temperatures in order to obtain reliable strength characteristics of cold-formed steel columns under fire conditions.

Cholesteryl ester transfer protein genotypes associated with venous thrombosis and dyslipoproteinemia in males

Although numerous genetic and acquired factors are appreciated as risk factors for venous thromboembolism (VTE) [1,2], only recently have male gender [3,4], dyslipoproteinemia [5], and silent atherosclerotic vascular disease [6] been linked to VTE. We recently found that high-density lipoprotein (HDL) deficiency is a key feature of a pattern of dyslipoproteinemia that is associated with VTE in males, and we found that the common TaqI B1 variation in the cholesteryl ester transfer protein (CETP) gene is significantly linked to VTE [5]. However, the TaqI B1/B2 single nucleotide polymorphism (SNP) itself is unlikely to affect directly CETP activity, but it is linked to nonsynonymous CETP SNPs Ala373Pro and Arg451Gln [7–9]. Here, we demonstrate that these two CETP variations are associated with VTE and low plasma HDL levels in males.

Cholesterol enhances phospholipid-dependent activated protein C anticoagulant activity

The influence of cholesterol on activated protein C (APC) anticoagulant activity in plasma and on factor Va inactivation was investigated. Anticoagulant and procoagulant activities of phosphatidylcholine/phosphatidylserine (PC/PS) vesicles containing cholesterol were assessed in the presence and absence of APC using factor Xa-1-stage clotting and factor Va inactivation assays. Cholesterol at approximate physiological membrane levels (30%) in PC/PS (60%/10% w/w) vesicles prolonged the factor Xa-1-stage clotting time dose-dependently in the presence of APC but not in the absence of APC. APC-mediated cleavage of purified recombinant factor Va variants that were modified at specific APC cleavage sites (Q306/Q679-factor Va; Q506/Q679-factor Va) was studied to define the effects of cholesterol on APC cleavage at R506 and R306. When compared to control PC/PS vesicles, cholesterol in PC/PS vesicles enhanced factor Va inactivation and the rate of APC cleavage at both R506 and R306. Cholesterol also enhanced APC cleavage rates at R306 in the presence of the APC cofactor, protein S. In summary, APC anticoagulant activity in plasma and factor Va inactivation as a result of cleavages at R506 and R306 by APC is markedly enhanced by cholesterol in phospholipid vesicles. These results suggest that cholesterol in a membrane surface may selectively enhance APC activities. © 2005 International Society on Thrombosis and Haemostasis.

Partial protection against chlamydial reproductive tract infection by a recombinant major outer membrane protein/CpG/cholera toxin intranasal vaccine in the guinea pig Chlamydia cavaie model

Chlamydia trachomatis is a major cause of sexually transmitted diseases worldwide. There currently is no vaccine to protect against chlamydial infection of the female reproductive tract. Vaccine development has predominantly involved using the murine model, however infection of female guinea pigs with Chlamydia caviae more closely resembles chlamydial infection of the human female reproductive tract, and presents a better model to assess potential human chlamydial vaccines. We immunised female guinea pigs intranasally with recombinant major outer membrane protein (r-MOMP) combined with CpG-10109 and cholera toxin adjuvants. Both systemic and mucosal immune responses were elicited in immunised animals. MOMP-specific IgG and IgA were present in the vaginal mucosae, and high levels of MOMP-specific IgG were detected in the serum of immunised animals. Antibodies from the vaginal mucosae were also shown to be capable of neutralising C. caviae in vitro. Following immunisation, animals were challenged intravaginally with a live C. caviae infection of 102 inclusion forming units. We observed a decrease in duration of infection and a significant (p<0.025) reduction in infection load in r-MOMP immunised animals, compared to animals immunised with adjuvant only. Importantly, we also observed a marked reduction in upper reproductive tract (URT) pathology in r-MOMP immunised animals. Intranasal immunisation of female guinea pigs with r-MOMP was able to provide partial protection against C. caviae infection, not only by reducing chlamydial burden but also URT pathology. This data demonstrates the value of using the guinea pig model to evaluate potential chlamydial vaccines for protection against infection and disease pathology caused by C. trachomatis in the female reproductive tract.

Double-shock control bump design optimization using hybridized evolutionary algorithms

This study investigates the application of two advanced optimization methods for solving active flow control (AFC) device shape design problem and compares their optimization efficiency in terms of computational cost and design quality. The first optimization method uses hierarchical asynchronous parallel multi-objective evolutionary algorithm and the second uses hybridized evolutionary algorithm with Nash-Game strategies (Hybrid-Game). Both optimization methods are based on a canonical evolution strategy and incorporate the concepts of parallel computing and asynchronous evaluation. One type of AFC device named shock control bump (SCB) is considered and applied to a natural laminar flow (NLF) aerofoil. The concept of SCB is used to decelerate supersonic flow on suction/pressure side of transonic aerofoil that leads to a delay of shock occurrence. Such active flow technique reduces total drag at transonic speeds which is of special interest to commercial aircraft. Numerical results show that the Hybrid-Game helps an EA to accelerate optimization process. From the practical point of view, applying a SCB on the suction and pressure sides significantly reduces transonic total drag and improves lift-to-drag (L/D) value when compared to the baseline design.