Collective excitations of trapped Bose-Einstein condensates in the energy and time domains

A time-dependent method for calculating the collective excitation frequencies and densities of a trapped, inhomogeneous Bose-Einstein condensate with circulation is presented. The results are compared with time-independent solutions of the Bogoliubov-de Gennes equations. The method is based on time-dependent linear-response theory combined with spectral analysis of moments of the excitation modes of interest. The technique is straightforward to apply, extremely efficient in our implementation with parallel fast Fourier transform methods, and produces highly accurate results. For high dimensionality or low symmetry the time-dependent approach is a more practical computational scheme and produces accurate and reliable data. The method is suitable for general trap geometries, condensate flows and condensates permeated with defects and vortex structures.

A topological algorithm for identification of structural domains of proteins

Background: Identification of the structural domains of proteins is important for our understanding of the organizational principles and mechanisms of protein folding, and for insights into protein function and evolution. Algorithmic methods of dissecting protein of known structure into domains developed so far are based on an examination of multiple geometrical, physical and topological features. Successful as many of these approaches are, they employ a lot of heuristics, and it is not clear whether they illuminate any deep underlying principles of protein domain organization. Other well-performing domain dissection methods rely on comparative sequence analysis. These methods are applicable to sequences with known and unknown structure alike, and their success highlights a fundamental principle of protein modularity, but this does not directly improve our understanding of protein spatial structure.

Molecular dissection of Meis1 reveals 2 domains required for leukemia induction and a key role for Hoxa gene activation

The Hoxa9 and Meis1 genes represent important oncogenic collaborators activated in a significant proportion of human leukemias with genetic alterations in the MLL gene. In this study, we show that the transforming property of Meis1 is modulated by 3 conserved domains, namely the Pbx interaction motif (PIM), the homeodomain, and the C-terminal region recently described to possess transactivating properties. Meis1 and Pbx1 interaction domain-swapping mutants are dysfunctional separately, but restore the full oncogenic activity of Meis1 when cotransduced in primary cells engineered to overexpress Hoxa9, thus implying a modular nature for PIM in Meis1-accelerated transformation. Moreover, we show that the transactivating domain of VP16 can restore, and even enhance, the oncogenic potential of the Meis1 mutant lacking the C-terminal 49 amino acids. In contrast to Meis1, the fusion VP16-Meis1 is spontaneously oncogenic, and all leukemias harbor genetic activation of endogenous Hoxa9 and/or Hoxa7, suggesting that Hoxa gene activation represents a key event required for the oncogenic activity of VP16-Meis1.

Platinum resistant cancer cells conserve sensitivity to BH3 domains and obatoclax induced mitochondrial apoptosis

Resistance to cisplatin chemotherapy remains a major hurdle preventing effective treatment of many solid cancers. BAX and BAK are pivotal regulators of the mitochondrial apoptosis pathway, however little is known regarding their regulation in cisplatin resistant cells. Cisplatin induces DNA damage in both sensitive and resistant cells, however the latter exhibits a failure to initiate N-terminal exposure of mitochondrial BAK or mitochondrial SMAC release. Both phenotypes are highly sensitive to mitochondrial permeabilisation induced by exogenous BH3 domain peptides derived from BID, BIM, NOXA (which targets MCL-1 and A1), and there is no significant change in their prosurvival BCL2 protein expression profiles. Obatoclax, a small molecule inhibitor of pro-survival BCL-2 family proteins including MCL-1, decreases cell viability irrespective of platinum resistance status across a panel of cell lines selected for oxaliplatin resistance. In summary, selection for platinum resistance is associated with a block of mitochondrial death signalling upstream of BAX/BAK activation. Conservation of sensitivity to BH3 domain induced apoptosis can be exploited by agents such as obatoclax, which directly target the mitochondria and BCL-2 family.

Unilateral Forgiveness and the Task of Reconciliation

Although forgiveness is often taken to bear a close connection to the value
of reconciliation, there is a good deal of scepticism about its role in situations where there is no consensus on the moral complexion of the past and no admission of guilt on the part of the perpetrator. This scepticism is typically rooted in the claims that forgiveness without perpetrator acknowledgement (1) aggravates the risk of recidivism; (2) yields a substandard and morally compromised form of political accommodation; and (3) comes across as patronizing and offensive to the recipient, thereby causing further alienation. In this article, my aim is to show, firstly, that none of these arguments is decisive and, secondly, that forgiveness is a suitable object of political concern in the
absence of cross-community consensus on the rights and wrongs of a conflict. In this way, I aim to demonstrate that forgiveness deserves to be taken seriously as a means to civic reconciliation in a broader range of situations than many have allowed.

Task prioritization in aging: effects of sensory information on concurrent posture and memory performance

In older adults, cognitive resources play a key role in maintaining postural stability. In the present study, we evaluated whether increasing postural instability using sway referencing induces changes in resource allocation in dual-task performance leading older adults to prioritize the more age-salient posture task over a cognitive task. Young and older adults participated in the study which comprised two sessions. In the first session, three posture tasks (stable, sway reference visual, sway reference somatosensory) and a working memory task (n-back) were examined. In the second session, single- and dual-task performance of posture and memory were assessed. Postural stability improved with session. Participants were more unstable in the sway reference conditions, and pronounced age differences were observed in the somatosensory sway reference condition. In dual-task performance on the stable surface, older adults showed an almost 40% increase in instability compared to single-task. However, in the sway reference somatosensory condition, stability was the same in single- and dual-task performance, whereas pronounced (15%) costs emerged for cognition. These results show that during dual-tasking while standing on a stable surface, older adults have the flexibility to allow an increase in instability to accommodate cognitive task performance. However, when instability increases by means of compromising somatosensory information, levels of postural control are kept similar in single- and dual-task, by utilizing resources otherwise allocated to the cognitive task. This evidence emphasizes the flexible nature of resource allocation, developed over the life-span to compensate for age-related decline in sensorimotor and cognitive processing.

Working Memory and Postural Control: Adult Age Differences in Potential for Improvement, Task Priority, and Dual Tasking

We investigate dynamic posture control and working memory (NBack) retest practice in young and older adults, focusing on older adults' potential for improvement in the component tasks but more importantly in dual-task performance. Participants performed the 2 tasks in 11 sessions under single- and dual-task conditions. Posture improvement was observed with retest practice for both groups. Increase in cognitive load after initial practice led to greater dual-task costs in both tasks in older adults and higher costs in memory in young adults. With continued practice, costs were reduced by both groups; however, the 2 groups focused improvement on different tasks: Older adults focused on posture but young adults on cognition. These results emphasize older adults' potential for improvement in dual-task performance and their flexibility to utilize the practice gains in posture to optimize cognitive performance.

Perceiving and acting upon spaces in a VR rugby task: Expertise effects in affordance detection and task achievement

This study used a virtual simulated 3vs3 rugby task to investigate whether gaps opening in particular running channels promote different actions by the ball-carrier player and whether an effect of rugby expertise is verified. We manipulated emergent gaps in three different locations: gap1 in the participant’s own running channel, gap 2 in the 1st receiver's running channel, and gap3 in the 2nd receiver's running channel. Recreational, intermediate, professional and non-rugby players performed the task. They could i) run with the ball, ii) make a short pass, or iii) make a long pass. All actions were digitally recorded. Results revealed that the emergence of gaps in the defensive line with respect to the participant’s own position significantly influenced action selection. Namely, ‘run’ was most often the action performed in gap 1, ‘short pass’ in gap 2, and ‘long pass’ in gap 3 trials. Furthermore, a strong positive relationship between expertise and task achievement was found.

Variation among nonclinical subjects on a line-bisection task

Absence of leftward bias in a line bisection task is often used as a clinical hemispheric indicator, but the effect is not uniform in a normal population. Sex, handedness, and strategy variables affect the strength and direction of any bias.

Distinct functional domains of the Salmonella enterica WbaP transferase that is involved in the initiation reaction for synthesis of the O antigen subunit

WbaP is a membrane enzyme that initiates O antigen synthesis in Salmonella enterica by catalysing the transfer of galactose 1-phosphate (Gal-1-P) onto undecaprenyl phosphate (Und-P). WbaP possesses at least three predicted structural domains: an N-terminal region containing four transmembrane helices, a large central periplasmic loop, and a C-terminal domain containing the last transmembrane helix and a large cytoplasmic tail. In this work, we investigated the contribution of each region to WbaP function by constructing a series of mutant WbaP proteins and using them to complement O antigen synthesis in DeltawbaP mutants of S. enterica serovars Typhi and Typhimurium. Truncated forms of WbaP lacking the periplasmic loop exhibited altered chain-length distributions in O antigen polymerization, suggesting that this central domain is involved in modulating the chain-length distribution of the O polysaccharide. The N-terminal and periplasmic domains were dispensable for complementation of O antigen synthesis in vivo, suggesting that the C-terminal domain carries the sugar-phosphate transferase activity. However, despite the fact that they complemented the synthesis of O antigen in the DeltawbaP mutant in vivo, membrane extracts containing WbaP derivatives without the N-terminal domain failed to transfer radioactive Gal from UDP-Gal into a lipid-rich fraction. These results suggest that the N-terminal region of WbaP, which contains four transmembrane domains, is essential for the insertion or stability of the protein in the bacterial membrane. We propose that the domain structure of WbaP enables this protein not only to function in the transfer of Gal-1-P to Und-P but also to establish critical interactions with additional proteins required for the correct assembly of O antigen in S. enterica.