61 research outputs found
Atropselective syntheses of (-) and (+) rugulotrosin A utilizing point-to-axial chirality transfer
Chiral, dimeric natural products containing complex structures and interesting biological properties have inspired chemists and biologists for decades. A seven-step total synthesis of the axially chiral, dimeric tetrahydroxanthone natural product rugulotrosin A is described. The synthesis employs a one-pot Suzuki coupling/dimerization to generate the requisite 2,2'-biaryl linkage. Highly selective point-to-axial chirality transfer was achieved using palladium catalysis with achiral phosphine ligands. Single X-ray crystal diffraction data were obtained to confirm both the atropisomeric configuration and absolute stereochemistry of rugulotrosin A. Computational studies are described to rationalize the atropselectivity observed in the key dimerization step. Comparison of the crude fungal extract with synthetic rugulotrosin A and its atropisomer verified that nature generates a single atropisomer of the natural product.P50 GM067041 - NIGMS NIH HHS; R01 GM099920 - NIGMS NIH HHS; GM-067041 - NIGMS NIH HHS; GM-099920 - NIGMS NIH HH
Characterization of K-Complexes and Slow Wave Activity in a Neural Mass Model
NREM sleep is characterized by two hallmarks, namely K-complexes (KCs) during sleep stage N2 and cortical slow oscillations (SOs) during sleep stage N3. While the underlying dynamics on the neuronal level is well known and can be easily measured, the resulting behavior on the macroscopic population level remains unclear. On the basis of an extended neural mass model of the cortex, we suggest a new interpretation of the mechanisms responsible for the generation of KCs and SOs. As the cortex transitions from wake to deep sleep, in our model it approaches an oscillatory regime via a Hopf bifurcation. Importantly, there is a canard phenomenon arising from a homoclinic bifurcation, whose orbit determines the shape of large amplitude SOs. A KC corresponds to a single excursion along the homoclinic orbit, while SOs are noise-driven oscillations around a stable focus. The model generates both time series and spectra that strikingly resemble real electroencephalogram data and points out possible differences between the different stages of natural sleep
Effective Rheology of Bubbles Moving in a Capillary Tube
We calculate the average volumetric flux versus pressure drop of bubbles
moving in a single capillary tube with varying diameter, finding a square-root
relation from mapping the flow equations onto that of a driven overdamped
pendulum. The calculation is based on a derivation of the equation of motion of
a bubble train from considering the capillary forces and the entropy production
associated with the viscous flow. We also calculate the configurational
probability of the positions of the bubbles.Comment: 4 pages, 1 figur
Modeling Brain Resonance Phenomena Using a Neural Mass Model
Stimulation with rhythmic light flicker (photic driving) plays an important role in the diagnosis of schizophrenia, mood disorder, migraine, and epilepsy. In particular, the adjustment of spontaneous brain rhythms to the stimulus frequency (entrainment) is used to assess the functional flexibility of the brain. We aim to gain deeper understanding of the mechanisms underlying this technique and to predict the effects of stimulus frequency and intensity. For this purpose, a modified Jansen and Rit neural mass model (NMM) of a cortical circuit is used. This mean field model has been designed to strike a balance between mathematical simplicity and biological plausibility. We reproduced the entrainment phenomenon observed in EEG during a photic driving experiment. More generally, we demonstrate that such a single area model can already yield very complex dynamics, including chaos, for biologically plausible parameter ranges. We chart the entire parameter space by means of characteristic Lyapunov spectra and Kaplan-Yorke dimension as well as time series and power spectra. Rhythmic and chaotic brain states were found virtually next to each other, such that small parameter changes can give rise to switching from one to another. Strikingly, this characteristic pattern of unpredictability generated by the model was matched to the experimental data with reasonable accuracy. These findings confirm that the NMM is a useful model of brain dynamics during photic driving. In this context, it can be used to study the mechanisms of, for example, perception and epileptic seizure generation. In particular, it enabled us to make predictions regarding the stimulus amplitude in further experiments for improving the entrainment effect
A Thalamocortical Neural Mass Model of the EEG during NREM Sleep and Its Response to Auditory Stimulation
Few models exist that accurately reproduce the complex rhythms of the thalamocortical system that are apparent in measured scalp EEG and at the same time, are suitable for large-scale simulations of brain activity. Here, we present a neural mass model of the thalamocortical system during natural non-REM sleep, which is able to generate fast sleep spindles (12–15 Hz), slow oscillations (<1 Hz) and K-complexes, as well as their distinct temporal relations, and response to auditory stimuli. We show that with the inclusion of detailed calcium currents, the thalamic neural mass model is able to generate different firing modes, and validate the model with EEG-data from a recent sleep study in humans, where closed-loop auditory stimulation was applied. The model output relates directly to the EEG, which makes it a useful basis to develop new stimulation protocols
Body Mass Index and Diabetes in Asia: A Cross-Sectional Pooled Analysis of 900,000 Individuals in the Asia Cohort Consortium
10.1371/journal.pone.0019930PLoS ONE66
Alignment of the ALICE Inner Tracking System with cosmic-ray tracks
37 pages, 15 figures, revised version, accepted by JINSTALICE (A Large Ion Collider Experiment) is the LHC (Large Hadron Collider) experiment devoted to investigating the strongly interacting matter created in nucleus-nucleus collisions at the LHC energies. The ALICE ITS, Inner Tracking System, consists of six cylindrical layers of silicon detectors with three different technologies; in the outward direction: two layers of pixel detectors, two layers each of drift, and strip detectors. The number of parameters to be determined in the spatial alignment of the 2198 sensor modules of the ITS is about 13,000. The target alignment precision is well below 10 micron in some cases (pixels). The sources of alignment information include survey measurements, and the reconstructed tracks from cosmic rays and from proton-proton collisions. The main track-based alignment method uses the Millepede global approach. An iterative local method was developed and used as well. We present the results obtained for the ITS alignment using about 10^5 charged tracks from cosmic rays that have been collected during summer 2008, with the ALICE solenoidal magnet switched off.Peer reviewe
Estimating the burden of selected non-communicable diseases in Africa: a systematic review of the evidence
Background
The burden of non-communicable diseases (NCDs) is rapidly increasing globally, and
particularly in Africa, where the health focus, until recently, has been on infectious diseases. The
response to this growing burden of NCDs in Africa has been affected owing to a poor
understanding of the burden of NCDs, and the relative lack of data and low level of research on
NCDs in the continent. Recent estimates on the burden of NCDs in Africa have been mostly
derived from modelling based on data from other countries imputed into African countries, and
not usually based on data originating from Africa itself. In instances where few data were
available, estimates have been characterized by extrapolation and over-modelling of the scarce
data. It is therefore believed that underestimation of NCDs burden in many parts of Africa cannot
be unexpected. With a gradual increase in average life expectancy across Africa, the region now
experiencing the fastest rate of urbanization globally, and an increase adoption of unhealthy
lifestyles, the burden of NCDs is expected to rise. This thesis will, therefore, be focussing on
understanding the prevalence, and/or where there are available data, the incidence, of four major
NCDs in Africa, which have contributed highly to the burden of NCDs, not only in Africa, but
also globally.
Methods
I conducted a systematic search of the literature on three main databases (Medline, EMBASE and
Global Health) for epidemiological studies on NCDs conducted in Africa. I retained and
extracted data from original population-based (cohort or cross sectional), and/or health service
records (hospital or registry-based studies) on prevalence and/or incidence rates of four major
NCDs in Africa. These include: cardiovascular diseases (hypertension and stroke), diabetes,
major cancer types (cervical, breast, prostate, ovary, oesophagus, bladder, Kaposi, liver, stomach,
colorectal, lung and non-Hodgkin lymphoma), and chronic respiratory diseases (chronic
obstructive pulmonary disease (COPD) and asthma). From extracted crude prevalence and
incidence rates, a random effect meta-analysis was conducted and reported for each NCD. An
epidemiological model was applied on all extracted data points. The fitted curve explaining the
largest proportion of variance (best fit) from the model was further applied. The equation
generated from the fitted curve was used to determine the prevalence and cases of the specific
NCD in Africa at midpoints of the United Nations (UN) population 5-year age-group population
estimates for Africa.
Results
From the literature search, studies on hypertension had the highest publication output at 7680, 92
of which were selected, spreading across 31 African countries. Cancer had 9762 publications and
39 were selected across 20 countries; diabetes had 3701 publications and 48 were selected across
28 countries; stroke had 1227 publications and 19 were selected across 10 countries; asthma had
790 publications and 45 were selected across 24 countries; and COPD had the lowest output with
243 publications and 13 were selected across 8 countries. From studies reporting prevalence
rates, hypertension, with a total sample size of 197734, accounted for 130.2 million cases and a
prevalence of 25.9% (23.5, 34.0) in Africa in 2010. This is followed by asthma, with a sample
size of 187904, accounting for 58.2 million cases and a prevalence of 6.6% (2.4, 7.9); COPD,
with a sample size of 24747, accounting for 26.3 million cases and a prevalence of 13.4% (9.4,
22.1); diabetes, with a sample size of 102517, accounting for 24.5 million cases and a prevalence
of 4.0% (2.7, 6.4); and stroke, with a sample size of about 6.3 million, accounting for 1.94
million cases and a prevalence of 317.3 per 100000 population (314.0, 748.2). From studies
reporting incidence rates, stroke accounted for 496 thousand new cases in Africa in 2010, with a
prevalence of 81.3 per 100000 person years (13.2, 94.9). For the 12 cancer types reviewed, a total
of 775 thousand new cases were estimated in Africa in 2010 from registry-based data covering a
total population of about 33 million. Among women, cervical cancer and breast cancer had 129
thousand and 81 thousand new cases, with incidence rates of 28.2 (22.1, 34.3) and 17.7 (13.0,
22.4) per 100000 person years, respectively. Among men, prostate cancer and Kaposi sarcoma
closely follows with 75 thousand and 74 thousand new cases, with incidence rates of 14.5 (10.9,
18.0) and 14.3 (11.9, 16.7) per 100000 person years, respectively.
Conclusion
This study suggests the prevalence rates of the four major NCDs reviewed (cardiovascular
diseases (hypertension and stroke), diabetes, major cancer types, and chronic respiratory diseases
(COPD and asthma) in Africa are high relative to global estimates. Due to the lack of data on
many NCDs across the continent, there are still doubts on the true prevalence of these diseases
relative to the current African population. There is need for improvement in health information
system and overall data management, especially at country level in Africa. Governments of
African nations, international organizations, experts and other stakeholders need to invest more
on NCDs research, particularly mortality, risk factors, and health determinants to have
evidenced-based facts on the drivers of this epidemic in the continent, and prompt better,
effective and overall public health response to NCDs in Africa
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Axonal velocity distributions in neural field equations.
Contains fulltext :
88463.pdf (publisher's version ) (Open Access)By modelling the average activity of large neuronal populations, continuum mean field models (MFMs) have become an increasingly important theoretical tool for understanding the emergent activity of cortical tissue. In order to be computationally tractable, long-range propagation of activity in MFMs is often approximated with partial differential equations (PDEs). However, PDE approximations in current use correspond to underlying axonal velocity distributions incompatible with experimental measurements. In order to rectify this deficiency, we here introduce novel propagation PDEs that give rise to smooth unimodal distributions of axonal conduction velocities. We also argue that velocities estimated from fibre diameters in slice and from latency measurements, respectively, relate quite differently to such distributions, a significant point for any phenomenological description. Our PDEs are then successfully fit to fibre diameter data from human corpus callosum and rat subcortical white matter. This allows for the first time to simulate long-range conduction in the mammalian brain with realistic, convenient PDEs. Furthermore, the obtained results suggest that the propagation of activity in rat and human differs significantly beyond mere scaling. The dynamical consequences of our new formulation are investigated in the context of a well known neural field model. On the basis of Turing instability analyses, we conclude that pattern formation is more easily initiated using our more realistic propagator. By increasing characteristic conduction velocities, a smooth transition can occur from self-sustaining bulk oscillations to travelling waves of various wavelengths, which may influence axonal growth during development. Our analytic results are also corroborated numerically using simulations on a large spatial grid. Thus we provide here a comprehensive analysis of empirically constrained activity propagation in the context of MFMs, which will allow more realistic studies of mammalian brain activity in the future.1 januari 201
Complex patterns arise through spontaneous symmetry breaking in dense homogeneous networks of neural oscillators
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