Living on the edge of stability, the limits of the nuclear landscape

A first-principles description of nuclear systems along the drip lines presents a substantial theoretical and computational challenge. In this paper, we discuss the nuclear theory roadmap, some of the key theoretical approaches, and present selected results with a focus on long isotopic chains. An important conclusion, which consistently emerges from these theoretical analyses, is that three-nucleon forces are crucial for both global nuclear properties and detailed nuclear structure, and that many-body correlations due to the coupling to the particle continuum are essential as one approaches particle drip lines. In the quest for a comprehensive nuclear theory, high performance computing plays a key role.Comment: Contribution to proceedings of Nobel Symposium 152: Physics with radioactive beams, June 2012, Gothenburg, Swede

Advances in Molecular Quantum Chemistry Contained in the Q-Chem 4 Program Package

A summary of the technical advances that are incorporated in the fourth major release of the Q-Chem quantum chemistry program is provided, covering approximately the last seven years. These include developments in density functional theory methods and algorithms, nuclear magnetic resonance (NMR) property evaluation, coupled cluster and perturbation theories, methods for electronically excited and open-shell species, tools for treating extended environments, algorithms for walking on potential surfaces, analysis tools, energy and electron transfer modelling, parallel computing capabilities, and graphical user interfaces. In addition, a selection of example case studies that illustrate these capabilities is given. These include extensive benchmarks of the comparative accuracy of modern density functionals for bonded and non-bonded interactions, tests of attenuated second order Møller–Plesset (MP2) methods for intermolecular interactions, a variety of parallel performance benchmarks, and tests of the accuracy of implicit solvation models. Some specific chemical examples include calculations on the strongly correlated Cr2 dimer, exploring zeolite-catalysed ethane dehydrogenation, energy decomposition analysis of a charged ter-molecular complex arising from glycerol photoionisation, and natural transition orbitals for a Frenkel exciton state in a nine-unit model of a self-assembling nanotube

International genome-wide meta-analysis identifies new primary biliary cirrhosis risk loci and targetable pathogenic pathways.

Primary biliary cirrhosis (PBC) is a classical autoimmune liver disease for which effective immunomodulatory therapy is lacking. Here we perform meta-analyses of discovery data sets from genome-wide association studies of European subjects (n=2,764 cases and 10,475 controls) followed by validation genotyping in an independent cohort (n=3,716 cases and 4,261 controls). We discover and validate six previously unknown risk loci for PBC (Pcombined<5 × 10(-8)) and used pathway analysis to identify JAK-STAT/IL12/IL27 signalling and cytokine-cytokine pathways, for which relevant therapies exist

Cortical edema in moderate fluid percussion brain injury is attenuated by vagus nerve stimulation

Development of cerebral edema (intracellular and/or extracellular water accumulation) following traumatic brain injury contributes to mortality and morbidity that accompanies brain injury. Chronic intermittent vagus nerve stimulation (VNS) initiated at either 2 h or 24 h (VNS: 30 s train of 0.5 mA, 20 Hz, biphasic pulses every 30 min) following traumatic brain injury enhances recovery of motor and cognitive function in rats in the weeks following brain injury; however, the mechanisms of facilitated recovery are unknown. The present study examines the effects of VNS on development of acute cerebral edema following unilateral fluid percussion brain injury (FPI) in rats, concomitant with assessment of their behavioral recovery. Two hours following FPI, VNS was initiated. Behavioral testing, using both beam walk and locomotor placing tasks, was conducted at 1 and 2 days following FPI. Edema was measured 48 h post-FPI by the customary method of region-specific brain weights before and after complete dehydration. Results of this study replicated that VNS initiated at 2 h after FPI: 1) effectively facilitated the recovery of vestibulomotor function at 2 days after FPI assessed by beam walk performance (P\u3c0.01); and 2) tended to improve locomotor placing performance at the same time point (P=0.18). Most interestingly, results of this study showed that development of edema within the cerebral cortex ipsilateral to FPI was significantly attenuated at 48 h in FPI rats receiving VNS compared with non-VNS FPI rats (P\u3c0.04). Finally, a correlation analysis between beam walk performance and cerebral edema following FPI revealed a significant inverse correlation between behavior performance and cerebral edema. Together, these results suggest that VNS facilitation of motor recovery following experimental brain injury in rats is associated with VNS-mediated attenuation of cerebral edema. © 2007 IBRO

Vagus nerve stimulation may protect GABAergic neurons following traumatic brain injury in rats: An immunocytochemical study

Seizures and subclinical seizures occur following experimental brain injury in rats and may result from inhibitory neuron loss. This study numerically compares cortical and hippocampal glutamic acid decarboxylase (GAD) positive neurons between sham fluid percussion injury (FPI), FPI with sham Vagus Nerve Simulation (VNS), and FPI with chronic intermittent VNS initiated at 24 h post FPI in rats. Rats (n = 8/group) were prepared for immunocytochemistry of GAD at 15 days post FPI. Serial sections were collected and GAD immunoreactive neurons were counted in the hippocampal hilus and two levels of the cerebral cortex. Numbers of quantifiable GAD cells in the rostral cerebral cortices were different between groups, both ipsilateral and contralateral to the FPI. Post hoc analysis of cell counts rostral to the ipsilateral epicenter, revealed a significant 26% reduction in the number of GAD cells/unit area of cerebral cortex following FPI. In the FPI-VNS group, this percentage loss was attenuated to only an 8.5% reduction, a value not significantly different from the sham group. In the contralateral side of the rostral cerebral cortex, FPI induced a significant 24% reduction in GAD cells/unit area; whereas, the VNS-treated rats showed no appreciable diminution of GAD cells rostral to the contralateral epicenter. Hippocampal analysis revealed a similar reduction of GAD cells in the FPI group; however, unlike the cortex this was not statistically significant. In the FPI-VNS group, a trend towards increased numbers of hilar GAD cells was observed, even over and above that of the sham FPI group; however, this was also not statistically significant. Together, these data suggest that VNS protects cortical GAD cells from death subsequent to FPI and may increase GAD cell counts in the hippocampal hilus of the injured brain. © 2006 Elsevier B.V. All rights reserved