Roles of the Bloom's syndrome helicase in the maintenance of genome stability

The RecQ family of DNA helicases is highly conserved in evolution from bacteria to humans. Of the five known human RecQ family members, three (BLM, WRN and RECQ4, which cause Bloom's syndrome, Werner's syndrome and Rothmund-Thomson syndrome respectively) are mutated in distinct clinical disorders associated with cancer predisposition and/or premature aging. BLM forms part of a multienzyme complex including topoisomerase IIIalpha, replication protein A and a newly identified factor called BLAP75. Together, these proteins play a role in the resolution of DNA structures that arise during the process of homologous recombination repair. In the absence of BLM, cells show genomic instability and a high incidence of sister-chromatid exchanges. In addition to a DNA structure-specific helicase activity, BLM also catalyses Holliday-junction branch migration and the annealing of complementary single-stranded DNA molecules

Exploring the magnetic properties of the largest single molecule magnets

The giant {Mn₇₀} and {Mn₈₄} wheels are the largest nuclearity single-molecule magnets synthesized to date, and understanding their magnetic properties poses a challenge to theory. Starting from first-principles calculations, we explore the magnetic properties and excitations in these wheels using effective spin Hamiltonians. We find that the unusual geometry of the superexchange pathways leads to weakly coupled {Mn₇} subunits carrying an effective S = 2 spin. The spectrum exhibits a hierarchy of energy scales and massive degeneracies, with the lowest-energy excitations arising from Heisenberg-ring-like excitations of the {Mn₇} subunits around the wheel. We further describe how weak longer-range couplings can select the precise spin ground-state of the Mn wheels out of the nearly degenerate ground-state band

Initial Geometrical Imperfections in Three-Storey Modular Steel Scaffolds

Modular steel scaffolds are commonly used as supporting scaffolds in building construction. They are highly susceptible to global and local instability, and traditionally, the load carrying capacities of these scaffolds are obtained from limited full-scale tests with little rational design. Structural failure of these scaffolds occurs from time to time due to inadequate design, poor installation and over-loads on sites. Initial geometrical imperfections are considered to be very important to the structural behaviour of multi-storey modular steel scaffolds. This paper presents an extensive numerical investigation on three different approaches in analyzing and designing multi-story modular steel scaffolds, namely, a) Notional Load Approach, b) Eigenmode Imperfection Approach, and c) Critical Load Approach. It should be noted that all these three approaches adopt different ways to allow for the presence of initial geometrical imperfections in the scaffolds when determining their load carrying capacities. Moreover, their suitability and accuracy in predicting the structural instability of typical modular steel scaffolds are presented and discussed in details

Finding diamonds in the rough: Targeted Sub-threshold Search for Strongly-lensed Gravitational-wave Events

Strong gravitational lensing of gravitational waves can produce duplicate signals separated in time with different amplitudes. We consider the case in which strong lensing produces identifiable gravitational-wave events and weaker sub-threshold signals hidden in the noise background. We present a search method for the sub-threshold signals using reduced template banks targeting specific confirmed gravitational-wave events. We apply the method to all events from Advanced LIGO's first and second observing run O1/O2. Using GW150914 as an example, we show that the method effectively reduces the noise background and raises the significance of (near-) sub-threshold triggers. In the case of GW150914, we can improve the sensitive distance by $2.0\% - 14.8\%$. Finally, we present the top $5$ possible lensed candidates for O1/O2 gravitational-wave events that passed our nominal significance threshold of False-Alarm-Rate $\leq 1/30$ days

Timeline mapping in qualitative interviews: a study of resilience with marginalized groups

Growing interest in visual timeline methods signals a need for critical engagement. Drawing on critical emancipatory epistemologies in our study exploring resilience among marginalized groups, we investigate how the creation of visual timelines informs verbal semistructured interviewing. We consider both how experiences of drawing timelines and how the role of the timeline in interviews varied for South Asian immigrant women who experienced domestic violence, and street-involved youth who experienced prior or recent violent victimization. Here we focus on three overarching themes developed through analysis of timelines: (a) rapport building, (b) participants as navigators, and (c) therapeutic moments and positive closure. In the discussion, we engage with the potential of visual timelines to supplement and situate semistructured interviewing, and illustrate how the framing of research is central to whether that research maintains a critical emancipatory orientation

Depleted pyrochlore antiferromagnets

I consider the class of "depleted pyrochlore" lattices of corner-sharing triangles, made by removing spins from a pyrochlore lattice such that every tetrahedron loses exactly one. Previously known examples are the "hyperkagome" and "kagome staircase". I give criteria in terms of loops for whether a given depleted lattice can order analogous to the kagome \sqrt{3} \times \sqrt{three} state, and also show how the pseudo-dipolar correlations (due to local constraints) generalize to even the random depleted case.Comment: 6pp IOP latex, 1 figure; Proc. "Highly Frustrated Magnetism 2008", Sept 2008, Braunschwei

Electrokinetic behavior of two touching inhomogeneous biological cells and colloidal particles: Effects of multipolar interactions

We present a theory to investigate electro-kinetic behavior, namely, electrorotation and dielectrophoresis under alternating current (AC) applied fields for a pair of touching inhomogeneous colloidal particles and biological cells. These inhomogeneous particles are treated as graded ones with physically motivated model dielectric and conductivity profiles. The mutual polarization interaction between the particles yields a change in their respective dipole moments, and hence in the AC electrokinetic spectra. The multipolar interactions between polarized particles are accurately captured by the multiple images method. In the point-dipole limit, our theory reproduces the known results. We find that the multipolar interactions as well as the spatial fluctuations inside the particles can affect the AC electrokinetic spectra significantly.Comment: Revised version with minor changes: References added and discussion extende

Characterization of a glucose-tolerant β-glucosidase from Anoxybacillus sp. DT3-1

Background: In general, biofuel production involves biomass pretreatment and enzymatic saccharification, followed by the subsequent sugar conversion to biofuel via fermentation. The crucial step in the production of biofuel from biomass is the enzymatic saccharification. Many of the commercial cellulase enzyme cocktails, such as Spezyme® CP (Genencor), Acellerase™ 1000 (Genencor), and Celluclast® 1.5L (Novozymes), are ineffectively to release free glucose from the pretreated biomass without additional β-glucosidase. Results: In this study, for the first time, a β-glucosidase DT-Bgl gene (1359 bp) was identified in the genome of Anoxybacillus sp. DT3-1, and cloned and heterologously expressed in Escherichia coli BL21. Phylogenetic analysis indicated that DT-Bgl belonged to glycosyl hydrolase (GH) family 1. The recombinant DT-Bgl was highly active on cello-oligosaccharides and p-nitrophenyl-β-d-glucopyranoside (pNPG). The DT-Bgl was purified using an Ni-NTA column, with molecular mass of 53 kDa using an SDS-PAGE analysis. It exhibited optimum activity at 70 °C and pH 8.5, and did not require any tested co-factors for activation. The K m and V max values for DT-Bgl were 0.22 mM and 923.7 U/mg, respectively, with pNPG as substrate. The DT-Bgl displayed high glucose tolerance, and retained 93 % activity in the presence of 10 M glucose. Conclusions: Anoxybacillus DT-Bgl is a novel thermostable β-glucosidase with low glucose inhibition, and converts long-chain cellodextrins to cellobiose, and further hydrolyse cellobiose to glucose. Results suggest that DT-Bgl could be useful in the development of a bioprocess for the efficient saccharification of lignocellulosic biomass