Diffusion on asymmetric fractal networks

We derive a renormalization method to calculate the spectral dimension $\bar{d}$ of deterministic self-similar networks with arbitrary base units and branching constants. The generality of the method allows the affect of a multitude of microstructural details to be quantitatively investigated. In addition to providing new models for physical networks, the results allow precise tests of theories of diffusive transport. For example, the properties of a class of non-recurrent trees ($\bar{d}>2$) with asymmetric elements and branching violate the Alexander Orbach scaling law

Methods development for Analysis of Partially Deglycosylated Proteins and Application to an HIV Envelope Protein Vaccine Candidate

The work presented herein describes the first comprehensive analysis of a partially deglycosylated HIV vaccine candidate envelope protein (Env). The Env, JRFL gp140 ΔCF, with 27 potential glycosylation sites, was partially deglycosylated with PNGase F as part of a strategy to generate a more immunogenic HIV vaccine, and the resulting protein’s glycosylation was characterized in a unique workflow using two different glycosidases, Endo H and Endo F3. This unique analysis protocol provided for coverage on 26 of the 27 glycosylation sites, and the data showed that the biochemical treatment with PNGase F resulted in a highly heterogeneous glycoprotein product that had been partially deglycosylated at most of the glycosylation sites. The protocols described in this work could be useful for characterizing the glycosylation site occupancy of other native or biochemically deglycosylated proteins

Bioavailability and biochemical effects of diclofenac sodium 0.1% ophthalmic solution in the domestic chicken (Gallus gallus domesticus)

Objective To determine if topical ophthalmic diclofenac sodium 0.1% solution alters renal parameters in the domestic chicken, and to determine if the drug is detectable in plasma after topical ophthalmic administration. Animals Thirty healthy domestic chickens Procedures Over seven days, 6 birds were treated unilaterally with 1 drop of artificial tear solution (group 1), 12 birds were treated unilaterally (group 2) and 12 bilaterally (group 3) with diclofenac sodium 0.1% ophthalmic solution. Treatments were provided for 7 days, every 12 hours in all groups. Pre- and post-treatment plasma samples from all birds were evaluated for changes in albumin, total protein, and uric acid. Post-treatment samples of all birds were also analyzed by HPLC-MS for detection of diclofenac sodium. Results Changes in pre- and post-treatment plasma albumin were significant (P \u3c 0.05) in groups 2 and 3, but not for group 1. Pre- and post-treatment changes in total protein and uric acid pre- and post-treatment were not significant for any group. Diclofenac sodium was not detectable (limit of detection = 0.10 ng/mL) in plasma samples from birds in group 1. Concentration of drug in group 3 was statistically greater than group 2 (P = 0.0008). Conclusions and Clinical Relevance Topical ophthalmic diclofenac sodium 0.1% administered every 12 hours in one or both eyes for 7 days is detectable in systemic circulation in the domestic chicken at 15 minutes post-administration, but did not cause overt changes in parameters used to monitor renal physiology

The UK, interrogation and Iraq, 2003-8

The UK’s interrogation operations during the conflict in Iraq (2003-8) are often portrayed by the media as involving significant amounts of mistreatment. The article demonstrates that these practices are not necessarily representative of the UK’s interrogation operations across this conflict. In doing so it contributes to the limited literature on the practice of interrogation and on the UK’s combat operations in Iraq. The UK’s interrogation capability, and therefore its intelligence-gathering capability, is shown to have rested primarily with the military’s Joint Forward Interrogation Team (JFIT). The JFIT suffered from limitations to the number, training and experience of its interrogators and interpreters. It is argued that maintaining a permanent, higher level of preparedness, for interrogation by the British armed forces is desirable

Geometry-controlled kinetics

It has long been appreciated that transport properties can control reaction kinetics. This effect can be characterized by the time it takes a diffusing molecule to reach a target -- the first-passage time (FPT). Although essential to quantify the kinetics of reactions on all time scales, determining the FPT distribution was deemed so far intractable. Here, we calculate analytically this FPT distribution and show that transport processes as various as regular diffusion, anomalous diffusion, diffusion in disordered media and in fractals fall into the same universality classes. Beyond this theoretical aspect, this result changes the views on standard reaction kinetics. More precisely, we argue that geometry can become a key parameter so far ignored in this context, and introduce the concept of "geometry-controlled kinetics". These findings could help understand the crucial role of spatial organization of genes in transcription kinetics, and more generally the impact of geometry on diffusion-limited reactions.Comment: Submitted versio

Decoding glutamate receptor activation by the Ca2+ sensor protein hippocalcin in rat hippocampal neurons

Hippocalcin is a Ca2+-binding protein that belongs to a family of neuronal Ca2+sensors and is a key mediator of many cellular functions including synaptic plasticity and learning. However, the molecular mechanisms involved in hippocalcin signalling remain illusive. Here we studied whether glutamate receptor activation induced by locally applied or synaptically released glutamate can be decoded by hippocalcin translocation. Local AMPA receptor activation resulted in fast hippocalcin-YFP translocation to specific sites within a dendritic tree mainly due to AMPA receptor-dependent depolarization and following Ca2+influx via voltage-operated calcium channels. Short local NMDA receptor activation induced fast hippocalcin-YFP translocation in a dendritic shaft at the application site due to direct Ca2+influx via NMDA receptor channels. Intrinsic network bursting produced hippocalcin-YFP translocation to a set of dendritic spines when they were subjected to several successive synaptic vesicle releases during a given burst whereas no translocation to spines was observed in response to a single synaptic vesicle release and to back-propagating action potentials. The translocation to spines required Ca2+influx via synaptic NMDA receptors in which Mg2+ block is relieved by postsynaptic depolarization. This synaptic translocation was restricted to spine heads and even closely (within 1–2 μm) located spines on the same dendritic branch signalled independently. Thus, we conclude that hippocalcin may differentially decode various spatiotemporal patterns of glutamate receptor activation into site- and time-specific translocation to its targets. Hippocalcin also possesses an ability to produce local signalling at the single synaptic level providing a molecular mechanism for homosynaptic plasticity

PIMMS: Photonic integrated multimode microspectrograph

We present the first integrated multimode photonic spectrograph, a device we call PIMMS #1. The device comprises a set of multimode fibres that convert to single-mode propagation using a matching set of photonic lanterns. These feed to a stack of cyclic array waveguides (AWGs) that illuminate a common detector. Such a device greatly reduces the size of an astronomical instrument at a fixed spectroscopic resolution. Remarkably, the PIMMS concept is largely independent of the telescope diameter, input focal ratio and entrance aperture - i.e. one size fits all! The instrument architecture can also exploit recent advances in astrophotonics (e.g. OH suppression fibres). We present a movie of the instrument's operation and discuss the advantages and disadvantages of this approach.9 page(s

A Group M Consensus Envelope Glycoprotein Induces Antibodies That Neutralize Subsets of Subtype B and C HIV-1 Primary Viruses

HIV-1 subtype C is the most common HIV-1 group M subtype in Africa and many parts of Asia. However, to date HIV-1 vaccine candidate immunogens have not induced potent and broadly neutralizing antibodies against subtype C primary isolates. We have used a centralized gene strategy to address HIV-1 diversity, and generated a group M consensus envelope gene with shortened consensus variable loops (CON-S) for comparative studies with wildtype (WT) Env immunogens. Our results indicate that the consensus HIV-1 group M CON-S Env elicited cross-subtype neutralizing antibodies of similar or greater breadth and titer than the WT Envs tested, indicating the utility of a centralized gene strategy. Our study also shows the feasibility of iterative improvements in Env immunogenicity by rational design of centralized genes