Inference of Temporally Varying Bayesian Networks

When analysing gene expression time series data an often overlooked but crucial aspect of the model is that the regulatory network structure may change over time. Whilst some approaches have addressed this problem previously in the literature, many are not well suited to the sequential nature of the data. Here we present a method that allows us to infer regulatory network structures that may vary between time points, utilising a set of hidden states that describe the network structure at a given time point. To model the distribution of the hidden states we have applied the Hierarchical Dirichlet Process Hideen Markov Model, a nonparametric extension of the traditional Hidden Markov Model, that does not require us to fix the number of hidden states in advance. We apply our method to exisiting microarray expression data as well as demonstrating is efficacy on simulated test data

Does visual flicker phase at gamma frequency modulate neural signal propagation and stimulus selection?

Oscillatory synchronization of neuronal populations has been proposed to play a role in perceptual integration and attentional processing. However, some conflicting evidence has been found with respect to its causal relevance for sensory processing, particularly when using flickering visual stimuli with the aim of driving oscillations. We tested psychophysically whether the relative phase of gamma frequency flicker (60 Hz) between stimuli modulates well-known facilitatory lateral interactions between collinear Gabor patches (Experiment 1) or crowding of a peripheral target by irrelevant distractors (Experiment 2). Experiment 1 assessed the impact of suprathreshold Gabor flankers on detection of a near-threshold central Gabor target (“Lateral interactions paradigm”). The flanking stimuli could flicker either in phase or in anti-phase with each other. The typical facilitation of target detection was found with collinear flankers, but this was unaffected by flicker phase. Experiment 2 employed a “crowding” paradigm, where orientation discrimination of a peripheral target Gabor patch is disrupted when surrounded by irrelevant distractors. We found the usual crowding effect, which declined with spatial separation, but this was unaffected by relative flicker phase between target and distractors at all separations. These results imply that externally driven manipulations of gamma frequency phase cannot modulate perceptual integration in vision

The Role of Industrialization and Renewable Energy on Environmental Quality in Oil Exporting Sub-Saharan African Countries

As countries grow, the call for achieving industrial sustainability becomes crucial for their development. As a result, this paper investigates the role of industrialization and renewable energy on environmental quality (proxied as load capacity factor) across seven (7) oil-exporting SSA countries between 1990 and 2023. Using cross-sectional dependence induced techniques such as panel-corrected standard error (PCSE) and feasible generalized least squares (FGLS), this study finds that while a unit increase in industrialization exacerbates environmental quality by 0.47 units, a unit increase in renewable energy plays an important role in improving environmental quality by 0.06 units. However, the amount of renewable energy consumption does not have the full potential to reduce the adverse environmental effects of industrialization. Further, the result indicates that while population reduces ecological quality, economic growth improves it. The study recommends that policymakers in oil-exporting countries should tailor their policies towards environmental regulation and encourage the use of eco-friendly technologies in the manufacturing sectors, through tax incentive policies, green industrial zones, and benchmarking ecological performance across these countries

Oscillatory mechanisms for controlling information flow in neural circuits

Mammalian brains generate complex, dynamic structures of oscillatory activity, in which distributed regions transiently engage in coherent oscillation, often at specific stages in behavioural or cognitive tasks. Much is now known about the dynamics underlying local circuit synchronisation and the phenomenology of where and when such activity occurs. While oscillations have been implicated in many high level processes, for most such phenomena we cannot say with confidence precisely what they are doing at an algorithmic or implementational level. This thesis presents work towards understanding the dynamics and possible function of large scale oscillatory network activity. We first address the question of how coherent oscillatory activity emerges between local networks by measuring phase response curves of an oscillating network in vitro. The network phase response curves provide mechanistic insight into inter-region synchronisation of local network oscillators. Highly simplified firing models are shown to reproduce the experimental data with remarkable accuracy. We then focus on one hypothesised computational function of network oscillations; flexibly controlling the gain of signal flow between anatomically connected networks. We investigate coding strategies and algorithmic operations that support flexible control of signal flow by oscillations, and their implementation by network dynamics. We identify two readout algorithms which selectively recover population rate coded signal with specific oscillatory modulations while ignoring other distracting inputs. By designing a spiking network model that implements one of these mechanisms, we demonstrate oscillatory control of signal flow in convergent pathways. We then investigate constraints on the structures of oscillatory activity that can be used to accurately and selectively control signal flow. Our results suggest that for inputs to be accurately distinguished from one another their oscillatory modulations must be close to orthogonal. This has implications for interpreting in vivo oscillatory activity, and may be an organising principle for the spatio-temporal structure of brain oscillations

Propagation of activity through the cortical hierarchy and perception are determined by neural variability

Brains are composed of anatomically and functionally distinct regions performing specialized tasks, but regions do not operate in isolation. Orchestration of complex behaviors requires communication between brain regions, but how neural dynamics are organized to facilitate reliable transmission is not well understood. Here we studied this process directly by generating neural activity that propagates between brain regions and drives behavior, assessing how neural populations in sensory cortex cooperate to transmit information. We achieved this by imaging two densely interconnected regions—the primary and secondary somatosensory cortex (S1 and S2)—in mice while performing two-photon photostimulation of S1 neurons and assigning behavioral salience to the photostimulation. We found that the probability of perception is determined not only by the strength of the photostimulation but also by the variability of S1 neural activity. Therefore, maximizing the signal-to-noise ratio of the stimulus representation in cortex relative to the noise or variability is critical to facilitate activity propagation and perception

Propagation of activity through the cortical hierarchy and perception are determined by neural variability

Brains are composed of anatomically and functionally distinct regions performing specialized tasks, but regions do not operate in isolation. Orchestration of complex behaviors requires communication between brain regions, but how neural dynamics are organized to facilitate reliable transmission is not well understood. Here we studied this process directly by generating neural activity that propagates between brain regions and drives behavior, assessing how neural populations in sensory cortex cooperate to transmit information. We achieved this by imaging two densely interconnected regions—the primary and secondary somatosensory cortex (S1 and S2)—in mice while performing two-photon photostimulation of S1 neurons and assigning behavioral salience to the photostimulation. We found that the probability of perception is determined not only by the strength of the photostimulation but also by the variability of S1 neural activity. Therefore, maximizing the signal-to-noise ratio of the stimulus representation in cortex relative to the noise or variability is critical to facilitate activity propagation and perception

Retention in an antiretroviral therapy programme during an era of decreasing drug cost in Limbe, Cameroon

<p>Abstract</p> <p>Background</p> <p>In 2002, Cameroon initiated scale up of antiretroviral therapy (ART); on 1 October 2004, a substantial reduction in ART cost occurred. We assessed the impact of this event and other factors on enrolment and retention in care among HIV-infected patients initiating ART from February 2002 to December 2005 at the single ART clinic serving the Southwest Region in Limbe, Cameroon.</p> <p>Methods</p> <p>We retrospectively analyzed clinical and pharmacy payment records of HIV-infected patients initiating ART according to national guidelines. We compared two cohorts of patients, enrolled before and after 1 October 2004, to determine if price reduction was associated with enhanced enrolment. We assessed factors associated with retention and survival by Cox proportional hazards models. Retention in care implied patients who had contact with the healthcare system as of 31 December 2005 (including those who were transferred to continue care in other ART centres), although these patients may have interrupted therapy at some time. A patient who was not retained in care may have dropped out (lost to follow up) or died.</p> <p>Results</p> <p>Mean enrolment rates for 2920 patients who initiated ART before and after the price reduction were 46.5 and 95.5 persons/month, respectively (p < 0.001). The probabilities of remaining alive and in care were 0.66 (95% CI 0.64-0.68) at six months, 0.58 (95% CI 0.56-0.60) at one year, 0.47 (95% CI 0.45-0.49) at two years and 0.35 (95% CI 0.32-0.38) at three years; they were not significantly different between the two cohorts of patients enrolled before and after the price reduction over the first 15 months of comparable follow up (hazard ratio 1.1; 95% CI 0.9-1.2, p = 0.27). In multivariable analysis using multiple imputations to compensate for missing values, factors associated with dropping out of care or dying were male gender (HR 1.33 [1.18-1.50], p = 0.003), treatment paid by self, family or partly by other (HR 3.05 [1.99-4.67], p < 0.001), and, compared with residents of Limbe, living more than 150 km from Limbe (HR 1.41 [1.18-1.69], p < 0.001), or being residents of Douala (HR 1.51 [1.16-1.98], p < 0.001).</p> <p>Conclusions</p> <p>Reducing the cost of ART increased enrolment of clients in the programme, but did not change retention in care. In a system where most clients pay for ART, an accessible clinic location may be more important than the cost of medication for retention in care. Decentralizing ART clinics might improve retention and survival among patients on ART.</p

The first myriapod genome sequence reveals conservative arthropod gene content and genome organisation in the centipede Strigamia maritima.

Myriapods (e.g., centipedes and millipedes) display a simple homonomous body plan relative to other arthropods. All members of the class are terrestrial, but they attained terrestriality independently of insects. Myriapoda is the only arthropod class not represented by a sequenced genome. We present an analysis of the genome of the centipede Strigamia maritima. It retains a compact genome that has undergone less gene loss and shuffling than previously sequenced arthropods, and many orthologues of genes conserved from the bilaterian ancestor that have been lost in insects. Our analysis locates many genes in conserved macro-synteny contexts, and many small-scale examples of gene clustering. We describe several examples where S. maritima shows different solutions from insects to similar problems. The insect olfactory receptor gene family is absent from S. maritima, and olfaction in air is likely effected by expansion of other receptor gene families. For some genes S. maritima has evolved paralogues to generate coding sequence diversity, where insects use alternate splicing. This is most striking for the Dscam gene, which in Drosophila generates more than 100,000 alternate splice forms, but in S. maritima is encoded by over 100 paralogues. We see an intriguing linkage between the absence of any known photosensory proteins in a blind organism and the additional absence of canonical circadian clock genes. The phylogenetic position of myriapods allows us to identify where in arthropod phylogeny several particular molecular mechanisms and traits emerged. For example, we conclude that juvenile hormone signalling evolved with the emergence of the exoskeleton in the arthropods and that RR-1 containing cuticle proteins evolved in the lineage leading to Mandibulata. We also identify when various gene expansions and losses occurred. The genome of S. maritima offers us a unique glimpse into the ancestral arthropod genome, while also displaying many adaptations to its specific life history.This work was supported by the following grants: NHGRIU54HG003273 to R.A.G; EU Marie Curie ITN #215781 “Evonet” to M.A.; a Wellcome Trust Value in People (VIP) award to C.B. and Wellcome Trust graduate studentship WT089615MA to J.E.G; Marine rhythms of Life” of the University of Vienna, an FWF (http://www.fwf.ac.at/) START award (#AY0041321) and HFSP (http://www.hfsp.org/) research grant (#RGY0082/2010) to KT-­‐R; MFPL Vienna International PostDoctoral Program for Molecular Life Sciences (funded by Austrian Ministry of Science and Research and City of Vienna, Cultural Department -­‐Science and Research to T.K; Direct Grant (4053034) of the Chinese University of Hong Kong to J.H.L.H.; NHGRI HG004164 to G.M.; Danish Research Agency (FNU), Carlsberg Foundation, and Lundbeck Foundation to C.J.P.G.; U.S. National Institutes of Health R01AI55624 to J.H.W.; Royal Society University Research fellowship to F.M.J.; P.D.E. was supported by the BBSRC via the Babraham Institute;This is the final version of the article. It first appeared from PLOS via http://dx.doi.org/10.1371/journal.pbio.100200