Conformational Dynamics of the Human Propeller Telomeric DNA Quadruplex on a Microsecond Time Scale

The human telomeric DNA sequence with four repeats can fold into a parallel-stranded propeller-type topology. NMR structures solved under molecular crowding experiments correlate with the crystal structures found with crystal-packing interactions that are effectively equivalent to molecular crowding. This topology has been used for rationalization of ligand design and occurs experimentally in a number of complexes with a diversity of ligands, at least in the crystalline state. While G-quartet stems have been well characterised, the interactions of the TTA loop with the G-quartets are much less defined. To better understand the conformational variability and structural dynamics of the propeller-type topology, we performed molecular dynamics simulations in explicit solvent up to 1.5 µs. The analysis provides a detailed atomistic account of the dynamic nature of the TTA loops highlighting their interactions with the G-quartets including formation of an A:A base pair, triad, pentad and hexad. The results present a threshold in quadruplex simulations, with regards to understanding the flexible nature of the sugar-phosphate backbone in formation of unusual architecture within the topology. Furthermore, this study stresses the importance of simulation time in sampling conformational space for this topology.

Agency Termination in Ireland: Culls and bonfires, or life after death?

The termination of state agencies has been a prominent aspect of administrative 'rationalization' programmes arising from the Global Financial Crisis. In this article, the frequency and type of agency terminations that have occurred in Ireland post-2008 are examined in longitudinal perspective. Following a consideration of agency types, the logic of agency rationalization is explored with a focus on the different ways in which agencies are terminated. Drawing on a unique dataset of Irish state agencies over a 90-year period, the article presents evidence concerning the degree to which terminations over the 2008-11 period differ, if at all, from those that have occurred previously. In concluding, the article proposes that rather than witnessing agency 'culls' and 'bonfires', there is 'life after death' for agencies and their work.

Synthesis, thermal characterization and rheological properties of a homologous series of polymethacrylate-based side-chain liquid crystal polymers

A new homologous series of side-chain liquid crystal polymers, the poly[omega-(4-cyanoazobenzene-4'-oxy)alkyl methacrylate]s, have been prepared in which the length of the flexible alkyl spacer is varied from 3 to 12 methylene units. All the polymers exhibit liquid crystalline behaviour; specifically, crystal E, smectic A and nematic phases are observed. The glass transition temperatures decrease on increasing spacer length before reaching a limiting value at ca. 30 degrees C. The clearing temperatures exhibit an odd-even effect on varying the length and parity of the spacer. This is attributed to the change in the average shape of the side chain as the parity of the spacer is varied. This rationalization also accounts for the observed alternation in the entropy change associated with the clearing transition. A weak relaxation is observed theologically for several members of this polymer series at temperatures above their respective glass transition temperatures. This is attributed either to specific motions of the smectic layers or to 180 degrees reorientational jumps of the long axis of the mesogenic unit about the polymer backbone. (C) 1997 Elsevier Science Ltd. All rights reserved.

Explanations for child sexual abuse given by convicted offenders in Malawi:no evidence for "HIV cleansing"

OBJECTIVE: A commonly cited, but unproven reason given for the rise in reported cases of child sexual abuse in Sub-Saharan Africa is the "HIV cleansing myth"-the belief that an HIV infected individual can be cured by having sex with a child virgin. The purpose of this study was to explore in Malawi the reasons given by convicted sex offenders for child sexual abuse and to determine if a desire to cure HIV infection motivated their offence.

METHODS: Offenders convicted of sexual crimes against victims under the age of 18 were interviewed in confidence in Malawi's two largest prisons. During the interview the circumstances of the crime were explored and the offenders were asked what had influenced them to commit it. Each participant was asked the closed question "Did you think that having sex with your victim would cure or cleanse you from HIV?"

RESULTS: 58 offenders agreed to participate. The median (range) age of offenders and victims was 30 (16-66) years and 14 (2-17) years, respectively. Twenty one respondents (36.2%) denied that an offence had occurred. Twenty seven (46.6%) admitted that they were motivated by a desire to satisfy their sexual desires. Six (10.3%) stated they committed the crime only because they were under the influence of drugs or alcohol. None of the participants said that a desire to cure or avoid HIV infection motivated the abuse.

CONCLUSION: This study suggests that offenders convicted of a sexual crime against children in Malawi were not motivated by a desire to be cured or "cleansed" from HIV infection. A need to fulfil their sexual urges or the disinhibiting effect of drugs or alcohol was offered by the majority of participants as excuses for their behaviour.

Reconsidering the Origins of Forsbergh Birefringence Patterns

In 1949, P. W. Forsbergh Jr. reported spontaneous spatial ordering in the birefringence patterns seen in flux-grown BaTiO3 crystals [1], under the transmission polarized light microscope [2]. Stunningly regular square-net arrays were often only found within a finite temperature window and could be induced on both heating and cooling, suggesting genuine thermodynamic stability. At the time, Forsbergh rationalized the patterns to have resulted from the impingement of ferroelastic domains, creating a complex tessellation of variously shaped domain packets. However, evidence for the intricate microstructural arrangement proposed by Forsbergh has never been found. Moreover, no robust thermodynamic argument has been presented to explain the region of thermal stability, its occurrence just below the Curie Temperature and the apparent increase in entropy associated with the loss of the Forsbergh pattern on cooling. As a result, despite decades of research on ferroelectrics, this ordering phenomenon and its thermodynamic origin have remained a mystery. In this paper, we re-examine the microstructure of flux-grown BaTiO3 crystals, which show Forsbergh birefringence patterns. Given an absence of any obvious arrays of domain polyhedra, or even regular shapes of domain packets, we suggest an alternative origin for the Forsbergh pattern, in which sheets of orthogonally oriented ferroelastic stripe domains simply overlay one another. We show explicitly that the Forsbergh birefringence pattern occurs if the periodicity of the stripe domains is above a critical value. Moreover, by considering well-established semiempirical models, we show that the significant domain coarsening needed to generate the Forsbergh birefringence is fully expected in a finite window below the Curie Temperature. We hence present a much more straightforward rationalization of the Forsbergh pattern than that originally proposed, in which exotic thermodynamic arguments are unnecessary.