Analysis and prediction of VH/VL packing in antibodies

The packing of VH and VL domains in antibodies can vary, influencing the topography of the antigen-combining site. However, until recently, this has largely been ignored in modelling antibody structure. We present an analysis of the degree of variability observed in known structures together with a machine-learning approach to predict the packing angle. A neural network was trained on sets of interface residues and a genetic algorithm designed to perform ‘feature selection' to define which sets of interface residues could be used most successfully to perform the prediction. While this training procedure was very computationally intensive, prediction is performed in a matter of seconds. Thus, not only do we provide a rapid method for predicting the packing angle, but also we define a set of residues that may be important in antibody humanization in order to obtain the correct binding site topograph

Novel Miniature Spectrometer for Remote Chemical Detection

A entirely new class of chemical sensors is being developed that will enable qualitative and quantitative remote, real-time, optical diagnostics of chemical species in hazardous gas, liquid, and semi-solid phases through a completely novel implementation of cavity ring-down spectroscopy. The sensor design uses a tiny, solid block (< 1cm3) of ultra-high purity optical material that is fabricated into a regular, planar polygon with a single convex facet to form a total-internal-reflection (TIR) ring minicavity. The lifetime of a light pulse that is injected into the cavity is extremely sensitive to chemical species in contact with the cavity. By using optical fiber to remotely locate the light source and detector, this new technology will permit high-sensitivity, remote chemical sensing with a rugged, cost-effective device

Association of EWS-FLI1 Type 1 Fusion with Lower Proliferative Rate in Ewing’s Sarcoma

The Ewing's sarcoma (ES) family of tumors, including peripheral neuroectodermal tumor (PNET), is defined genetically by specific chromosomal translocations resulting in fusion of the EWS gene with a member of the ETS family of transcription factors, either FLI1 (90-95%) or ERG (5-10%). A second level of molecular genetic heterogeneity stems from the variation in the location of the translocation breakpoints, resulting in the inclusion of different combinations of exons from EWS and FLI1 (or ERG) in the fusion products. The most common type of EWS-FLI1 fusion transcript, type 1, is associated with a favorable prognosis and appears to encode a functionally weaker transactivator, compared to other fusion types. We sought to determine whether the observed covariation of structure, function, and clinical course correlates with tumor cell kinetic parameters such as proliferative rate and apoptosis, and with expression of the receptor for insulin-like growth factor I (IGF-1R). In a group of 86 ES/PNET with defined EWS-ETS fusions (45 EWS-FLI1 type 1, 27 EWS-FLI1 non-type 1, 14 EWS-ERG), we assessed proliferation rate by immunostaining for Ki-67 using MIB1 antibody (n = 85), apoptosis by TUNEL assay (n = 66), and IGF-1R expression by immunostaining with antibody 1H7 (n = 78). Ki-67 proliferative index was lower in tumors with EWS-FLI1 type 1 than those with non-type 1 EWS-FLI1, whether analyzed as a continuous (P = 0.049) or categorical (P = 0.047) variable. Logistic regression analysis suggests that this association was secondary to the association of type 1 EWS-FLI1 and lower IGF-1R expression (P = 0.04). Comparing EWS-FLI1 to EWS-ERG cases, Ki-67 proliferative index was higher in the latter (P = 0.01, Mann-Whitney test; P = 0.02, Fisher's exact test), but there was no significant difference in IGF-1R. TUNEL results showed no significant differences between groups. Our results suggest that clinical and functional differences between alternative forms of EWS-FLI1 are paralleled by differences in proliferative rate, possibly mediated by differential regulation of the IGF-1R pathway

Double-magic nature of 132Sn and 208Pb through lifetime and cross-section measurements

Single-neutron states in Sn133 and Pb209, which are analogous to single-electron states outside of closed atomic shells in alkali metals, were populated by the (Be9, Be8) one-neutron transfer reaction in inverse kinematics using particle-γ coincidence s

Transient field g factor and mean-life measurements with a rare isotope beam of 126Sn

Background: The g factors and lifetimes of the 21+ states in the stable, proton-rich Sn isotopes have been measured, but there is scant information on neutron-rich Sn isotopes. Purpose: Measurement of the g factor and the lifetime of the 21+ state at 1.141 MeV in neutron-rich 126Sn (T1/2=2. 3×105y). Method: Coulomb excitation in inverse kinematics together with the transient field and the Doppler shift attenuation techniques were applied to a radioactive beam of 126Sn at the Holifield Radioactive Ion Beam Facility. Results: g(21+)=-0.25(21) and τ(21+)=1.5(2) ps were obtained. Conclusions: The data are compared to large-scale shell-model and quasiparticle random-phase calculations. Neutrons in the h11/2 and d3/2 orbitals play an important role in the structure of the 21+ state of 126Sn. Challenges, limitations, and implications for such experiments at future rare isotope beam facilities are discussed

Electromagnetic properties of the 21+ state in 134Te: Influence of core excitation on single-particle orbits beyond 132Sn

The g factor and B(E2) of the first excited 2+ state have been measured following Coulomb excitation of the neutron-rich semimagic nuclide 134Te (two protons outside 132Sn) produced as a radioactive beam. The precision achieved matches related g-factor m

Cysteine ligand vibrations are responsible for the complex resonance Raman spectrum of azurin

Biophysical Structural ChemistryMicrobial Biotechnolog

Cosmological Perturbations in a Big Crunch/Big Bang Space-time

A prescription is developed for matching general relativistic perturbations across singularities of the type encountered in the ekpyrotic and cyclic scenarios i.e. a collision between orbifold planes. We show that there exists a gauge in which the evolution of perturbations is locally identical to that in a model space-time (compactified Milne mod Z_2) where the matching of modes across the singularity can be treated using a prescription previously introduced by two of us. Using this approach, we show that long wavelength, scale-invariant, growing-mode perturbations in the incoming state pass through the collision and become scale-invariant growing-mode perturbations in the expanding hot big bang phase.Comment: 47 pages, 4 figure

Transitional experiences of post-16 sports education: Jack's story

This paper explores the layered transitional experiences of a semi-professional athlete named Jack (a pseudonym) between the fields of professional sport and further and higher education. Our analysis is framed by the quadripartite framework of structuration and focuses on Jack's 'in-situ' practices at his college and university in order to illustrate how these can operate to reproduce, transform, and challenge the habitual discourses and rituals that circulate within these institutions by generating forms of corporeal empowerment for young athletes who have valued conjunctural knowledge. The findings highlight the fragility of the transition process and raise questions regarding how the experiences of young people are shaped by the relationships between employment and post-16 education. Jack's experiences have implications for both policy and practice within further education and higher education. © 2012 © 2012 Taylor & Francis