Tackling Exascale Software Challenges in Molecular Dynamics Simulations with GROMACS

GROMACS is a widely used package for biomolecular simulation, and over the last two decades it has evolved from small-scale efficiency to advanced heterogeneous acceleration and multi-level parallelism targeting some of the largest supercomputers in the world. Here, we describe some of the ways we have been able to realize this through the use of parallelization on all levels, combined with a constant focus on absolute performance. Release 4.6 of GROMACS uses SIMD acceleration on a wide range of architectures, GPU offloading acceleration, and both OpenMP and MPI parallelism within and between nodes, respectively. The recent work on acceleration made it necessary to revisit the fundamental algorithms of molecular simulation, including the concept of neighborsearching, and we discuss the present and future challenges we see for exascale simulation - in particular a very fine-grained task parallelism. We also discuss the software management, code peer review and continuous integration testing required for a project of this complexity.Comment: EASC 2014 conference proceedin

The Rho GDI Rdi1 regulates Rho GTPases by distinct mechanisms

© 2008 by The American Society for Cell Biology. Under the License and Publishing Agreement, authors grant to the general public, effective two months after publication of (i.e.,. the appearance of) the edited manuscript in an online issue of MBoC, the nonexclusive right to copy, distribute, or display the manuscript subject to the terms of the Creative Commons–Noncommercial–Share Alike 3.0 Unported license (http://creativecommons.org/licenses/by-nc-sa/3.0).The small guanosine triphosphate (GTP)-binding proteins of the Rho family are implicated in various cell functions, including establishment and maintenance of cell polarity. Activity of Rho guanosine triphosphatases (GTPases) is not only regulated by guanine nucleotide exchange factors and GTPase-activating proteins but also by guanine nucleotide dissociation inhibitors (GDIs). These proteins have the ability to extract Rho proteins from membranes and keep them in an inactive cytosolic complex. Here, we show that Rdi1, the sole Rho GDI of the yeast Saccharomyces cerevisiae, contributes to pseudohyphal growth and mitotic exit. Rdi1 interacts only with Cdc42, Rho1, and Rho4, and it regulates these Rho GTPases by distinct mechanisms. Binding between Rdi1 and Cdc42 as well as Rho1 is modulated by the Cdc42 effector and p21-activated kinase Cla4. After membrane extraction mediated by Rdi1, Rho4 is degraded by a novel mechanism, which includes the glycogen synthase kinase 3β homologue Ygk3, vacuolar proteases, and the proteasome. Together, these results indicate that Rdi1 uses distinct modes of regulation for different Rho GTPases.Deutsche Forschungsgemeinschaf

Antiferromagnetic Order Induced by an Applied Magnetic Field in a High-Temperature Superconductor

One view of the cuprate high-transition temperature (high-Tc) superconductors is that they are conventional superconductors where the pairing occurs between weakly interacting quasiparticles, which stand in one-to-one correspondence with the electrons in ordinary metals - although the theory has to be pushed to its limit. An alternative view is that the electrons organize into collective textures (e.g. charge and spin stripes) which cannot be mapped onto the electrons in ordinary metals. The phase diagram, a complex function of various parameters (temperature, doping and magnetic field), should then be approached using quantum field theories of objects such as textures and strings, rather than point-like electrons. In an external magnetic field, magnetic flux penetrates type-II superconductors via vortices, each carrying one flux quantum. The vortices form lattices of resistive material embedded in the non-resistive superconductor and can reveal the nature of the ground state - e.g. a conventional metal or an ordered, striped phase - which would have appeared had superconductivity not intervened. Knowledge of this ground state clearly provides the most appropriate starting point for a pairing theory. Here we report that for one high-Tc superconductor, the applied field which imposes the vortex lattice, also induces antiferromagnetic order. Ordinary quasiparticle pictures cannot account for the nearly field-independent antiferromagnetic transition temperature revealed by our measurements

IL-22 mediates goblet cell hyperplasia and worm expulsion in intestinal helminth infection.

Type 2 immune responses are essential in protection against intestinal helminth infections. In this study we show that IL-22, a cytokine important in defence against bacterial infections in the intestinal tract, is also a critical mediator of anti-helminth immunity. After infection with Nippostrongylus brasiliensis, a rodent hookworm, IL-22-deficient mice showed impaired worm expulsion despite normal levels of type 2 cytokine production. The impaired worm expulsion correlated with reduced goblet cell hyperplasia and reduced expression of goblet cell markers. We further confirmed our findings in a second nematode model, the murine whipworm Trichuris muris. T.muris infected IL-22-deficient mice had a similar phenotype to that seen in N.brasiliensis infection, with impaired worm expulsion and reduced goblet cell hyperplasia. Ex vivo and in vitro analysis demonstrated that IL-22 is able to directly induce the expression of several goblet cell markers, including mucins. Taken together, our findings reveal that IL-22 plays an important role in goblet cell activation, and thus, a key role in anti-helminth immunity

Aberrant iPSC-derived human astrocytes in Alzheimer's disease

The pathological potential of human astroglia in Alzheimer's disease (AD) was analysed in vitro using induced pluripotent stem cell (iPSC) technology. Here, we report development of a human iPSC-derived astrocyte model created from healthy individuals and patients with either early-onset familial AD (FAD) or the late-onset sporadic form of AD (SAD). Our chemically-defined and highly efficient model provides >95% homogeneous populations of human astrocytes within 30 days of differentiation from cortical neural progenitor cells (NPCs). All astrocytes expressed functional markers including; glial fibrillary acidic protein (GFAP), excitatory amino acid transporter 1 (EAAT1), S100B and glutamine synthetase (GS) comparable to that of adult astrocytes in vivo. However, induced astrocytes derived from both SAD and FAD patients exhibit a pronounced pathological phenotype, with a significantly less complex morphological appearance, overall atrophic profiles, and abnormal localisation of key functional astroglial markers. Furthermore, NPCs derived from identical patients did not show any differences, therefore, validating that remodelled astroglia are not as a result of defective neuronal intermediates. This work not only presents a novel model to study the mechanisms of human astrocytes in vitro, but also provides an ideal platform for further interrogation of early astroglial cell-autonomous events in AD and the possibility of identification of novel therapeutic targets for the treatment of AD

The Role of Negotiation in Privacy-Enhanced E-Commerce Transactions

Online vendors use personal information to deliver customized services efficiently to their customers. Both users and vendors value the relationship building made possible using personal data. However, the use of personally identifying data gives rise to the potential for privacy invasion. When consumers must disclose personal information, they are forced to perform a risk-benefit analysis in which the risks of disclosing one\u27s personal information are weighted against the potential benefits of the disclosure. While some researchers note that consumers maximize benefits in deciding whether to disclose personal information, others argue that consumers lack sufficient information and power to make educated, balanced decisions regarding disclosing their private information. We add to the privacy discussion by arguing that a real negotiation position for both parties can help realize the full benefits of online personalization. We propose a model for mitigating the tension between the benefits of personalization and the risks to privacy invasion. This framework informs our future work which seeks to develop rich and deep understandings of negotiated, privacy-concerned personalization

Police views of suicidal persons and the law criminalizing attempted suicide in Ghana: A qualitative study with policy implications

The penal code of Ghana condemns suicide attempt. The present study sought to explore the views of the police on persons who attempt suicide and the law criminalizing the act. Qualitative in-depth interviews were used to explore the views of 18 officers of the Ghana Police Service. Data were analyzed using thematic analysis technique. Findings showed that the police officers profiled suicide attempters as needy, enigmatic, ignorant, and blameworthy. Majority (n = 14) of them disagreed with the law and suggested a repeal, whereas only four of them agreed with the law. Regardless of their positions on criminalization, they showed an inclination to help, rather than arrest, when confronted with such persons in line of their duty. Educating the police on suicidal behavior may help to deepen their understanding and help improve the way they handle suicidal persons. This may also strengthen police suicide prevention gatekeeping obligations