Comparison of the modelled thyroxine binding site in TBG with the experimentally determined site in transthyretin

The structure of cleaved thyroxine-binding globulin (TBG) hasbeen modelled on the crystal structure of cleaved 1-antitrypsin(a member of the serine proteinase inhibitor, serpin, superfamily)based on the high sequence homology exhibited by the two proteins.Particular attention was paid to the identification and modelledcharacteristics of the thyroxine binding site. The primary aimof the study was to compare the site qualitatively with thecrystallographically determined binding site of transthyretin,the other major transporter of thyroxine, in an attempt to explainthe higher binding affinity of the site compared with the knownthyrox ine binding site in transthyretin (10¹⁰ versus 10⁸ M^–1).The proposed binding site shares some similar characteristicswith the transthyretin binding site but also includes a clusterof aromatic residues which are entirely absent in transthyretin.It is proposed that this might account for the substantial differencein binding affinities.     

MOCVD Growth of Doped GaAs/AlGaAs Quantum Heterostructures

The influences of growth techniques of AP-MOCVD GaAs/AlGaAs silicon-doped multi-quantum wells(MQWs), heterostructure bipolar transistors (HBTs), double barrier resonant tunneling diodes(DBRTDs) ontheir structures and performances were studied. Continuously grown MQWs, that is, no growth interruption atthe heterointerfaces, shown blue-shifted, narrower and stronger photoluminescence(PL) compared withinterruptedly grown ones.TEM examination of the interrupted interfaces revealed a bright line correspondingto the compositional fluctuation and impurity adsorption, and indicated noncommutative structures ofAlGaAs/GaAs and GaAs/AlGaAs interfaces. High performance HBTs and DBRTDs were obtained bycontinuously grown method while growth interruption caused performance degradation. It was concluded thatgrowth interruption may cause accumulation of residua1 impurities in the ambient as well as compositionalfluctuation while continuous growth at very low growth rates can overcome such problems.     

Subroutine based detection of APT malware

Statistical detection of mass malware has been shown to be highly successful. However, this type of malware is less interesting to cyber security officers of larger organizations, who are more concerned with detecting malware indicative of a targeted attack. Here we investigate the potential of statistically based approaches to detect such malware using a malware family associated with a large number of targeted network intrusions. Our approach is complementary to the bulk of statistical based malware classifiers, which are typically based on measures of overall similarity between executable files. One problem with this approach is that a malicious executable that shares some, but limited, functionality with known malware is likely to be misclassified as benign. Here a new approach to malware classification is introduced that classifies programs based on their similarity with known malware subroutines. It is illustrated that malware and benign programs can share a substantial amount of code, implying that classification should be based on malicious subroutines that occur infrequently, or not at all in benign programs. Various approaches to accomplishing this task are investigated, and a particularly simple approach appears the most effective. This approach simply computes the fraction of subroutines of a program that are similar to malware subroutines whose likes have not been found in a larger benign set. If this fraction exceeds around 1.5 %, the corresponding program can be classified as malicious at a 1 in 1000 false alarm rate. It is further shown that combining a local and overall similarity based approach can lead to considerably better prediction due to the relatively low correlation of their predictions.     

Quantitative mass spectrometry for colorectal cancer proteomics

This review documents the uses of quantitative MS applied to colorectal cancer (CRC) proteomics for biomarker discovery and molecular pathway profiling. Investigators are adopting various labeling and label-free MS approaches to quantitate differential protein levels in cells, tumors, and plasma/serum. We comprehensively review recent uses of this technology to examine mouse models of CRC, CRC cell lines, their secretomes and subcellular fractions, CRC tumors, CRC patient plasma/serum, and stool samples. For biomarker discovery these approaches are uncovering proteins with potential diagnostic and prognostic utility, while in vitro cell culture experiments are characterizing proteomic and phosphoproteomic responses to disrupted signaling pathways due to mutations or to inhibition of drugable enzymes.     

Slow-flow measurements and fluid dynamics analysis using the Fresnel drag effect

We have employed a Sagnac interferometer to measure small optical phase shifts induced by the Fresnel drag effect on moving media. The system detects volumetric flow rates of water as slow as 43 μL/min while maintaining a small pressure drop across the measuring pipe. Velocity profiles and turbulence measurements of flowing water are also demonstrated and discussed.     

Application of the boundary integral method to the interaction of rising two-dimensional deformable gas bubbles

The boundary integral method is applied to model the initial motion of two-dimensional or cylindrical deformable gas bubbles in an inviscid, incompressible fluid. Following the success of recent boundary integral studies to predict the qualitative behaviour of a single gas bubble, this numerical study is extended to consider the interaction of several bubbles. Surface tension, relative initial position and volume are all found to be important factors affecting the bubble interaction, jet formation, trapping of fluid between bubbles and bubble shedding. As well as computing the evolution of the bubble surfaces, consideration of the pressure fields and resulting instantaneous streamlines is given.     

Psychosexual development of women with congenital adrenal hyperplasia

Women with congenital adrenal hyperplasia (CAH) (N = 31) and their unaffected sisters or female cousins (N = 15) participated in a study of psychosexual development. All participants were > or = 18 years of age (mean age, 25 years; range, 18-40). Comparisons were also made between the CAH women with the salt-wasting (SW) form of the disorder and those with simple virilization (SV). A psychosexual assessment protocol examined six variables: (1) sex assignment at birth (probands only); (2) recalled sex-typed behavior during childhood; (3) gender identity and gender role identification in adulthood; (4) relationship status; (5) sexual orientation in fantasy; and (6) sexual orientation in behavior. Salt-wasting status and sex assignment at birth were also ascertained for the CAH women who either refused to participate in the study (N = 10) or could not be traced (N = 13). Compared to the controls, the women with CAH recalled more cross-gender role behavior and less comfort with their sense of "femininity" during childhood. The two groups did not differ in degree of gender dysphoria in adulthood, although the probands showed more cross-gender role identification. Three of the nonparticipant probands were living, as adults, in the male social role (2 reared from birth as boys and 1 who changed from the female to the male social role during adolescence). The CAH women and the controls did not differ in relationship status (married/cohabiting vs. single). The CAH women had lower rates of exclusive heterosexual fantasy and fewer sexual experiences with men than the controls; however, the CAH women did not have more sexual experiences with women than the controls. Comparisons between the SW and SV revealed several differences: the SW were less likely to be assigned to the female sex at birth, recalled more cross-gender role behavior during childhood, were less likely to be married or cohabiting, and had lower rates of sexual experiences with men. The results were discussed in relation to the effects of prenatal androgens on psychosexual differentiation.