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Description
Zoonotic pathogens that cause leprosy (Mycobacterium leprae) and tuberculosis (Mycobacterium tuberculosis complex, MTBC) continue to impact modern human populations. Therefore, methods able to survey mycobacterial infection in potential animal hosts are necessary for proper evaluation of human exposure threats. Here we tested for mycobacterial-specific single- and multi-copy loci using qPCR.

Zoonotic pathogens that cause leprosy (Mycobacterium leprae) and tuberculosis (Mycobacterium tuberculosis complex, MTBC) continue to impact modern human populations. Therefore, methods able to survey mycobacterial infection in potential animal hosts are necessary for proper evaluation of human exposure threats. Here we tested for mycobacterial-specific single- and multi-copy loci using qPCR. In a trial study in which armadillos were artificially infected with M. leprae, these techniques were specific and sensitive to pathogen detection, while more traditional ELISAs were only specific. These assays were then employed in a case study to detect M. leprae as well as MTBC in wild marmosets. All marmosets were negative for M. leprae DNA, but 14 were positive for the mycobacterial rpoB gene assay. Targeted capture and sequencing of rpoB and other MTBC genes validated the presence of mycobacterial DNA in these samples and revealed that qPCR is useful for identifying mycobacterial-infected animal hosts.
Created2015-11-16
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Description

Background
In 2015, the Zika arbovirus (ZIKV) began circulating in the Americas, rapidly expanding its global geographic range in explosive outbreaks. Unusual among mosquito-borne diseases, ZIKV has been shown to also be sexually transmitted, although sustained autochthonous transmission due to sexual transmission alone has not been observed, indicating the reproduction number

Background
In 2015, the Zika arbovirus (ZIKV) began circulating in the Americas, rapidly expanding its global geographic range in explosive outbreaks. Unusual among mosquito-borne diseases, ZIKV has been shown to also be sexually transmitted, although sustained autochthonous transmission due to sexual transmission alone has not been observed, indicating the reproduction number (R0) for sexual transmission alone is less than 1. Critical to the assessment of outbreak risk, estimation of the potential attack rates, and assessment of control measures, are estimates of the basic reproduction number, R0.
Methods
We estimated the R0 of the 2015 ZIKV outbreak in Barranquilla, Colombia, through an analysis of the exponential rise in clinically identified ZIKV cases (n = 359 to the end of November, 2015).
Findings
The rate of exponential rise in cases was ρ = 0.076 days[superscript −1], with 95% CI [0.066,0.087] days[superscript −1]. We used a vector-borne disease model with additional direct transmission to estimate the R0; assuming the R0 of sexual transmission alone is less than 1, we estimated the total R0 = 3.8 [2.4,5.6], and that the fraction of cases due to sexual transmission was 0.23 [0.01,0.47] with 95% confidence.
Interpretation
This is among the first estimates of R0 for a ZIKV outbreak in the Americas, and also among the first quantifications of the relative impact of sexual transmission.

Created2016-10-17
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Description
We studied left ventricular flow patterns for a range of rotational orientations of a bileaflet mechanical heart valve (MHV) implanted in the mitral position of an elastic model of a beating left ventricle (LV). The valve was rotated through 3 angular positions (0, 45, and 90 degrees) about the LV

We studied left ventricular flow patterns for a range of rotational orientations of a bileaflet mechanical heart valve (MHV) implanted in the mitral position of an elastic model of a beating left ventricle (LV). The valve was rotated through 3 angular positions (0, 45, and 90 degrees) about the LV long axis. Ultrasound scans of the elastic LV were obtained in four apical 2-dimensional (2D) imaging projections, each with 45 degrees of separation. Particle imaging velocimetry was performed during the diastolic period to quantify the in-plane velocity field obtained by computer tracking of diluted microbubbles in the acquired ultrasound projections. The resulting velocity field, vorticity, and shear stresses were statistically significantly altered by angular positioning of the mechanical valve, although the results did not show any specific trend with the valve angular position and were highly dependent on the orientation of the imaging plane with respect to the valve. We conclude that bileaflet MHV orientation influences hemodynamics of LV filling. However, determination of ‘optimal’ valve orientation cannot be made without measurement techniques that account for the highly 3-dimensional (3D) intraventricular flow.
Created2015-06-26
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Description
pH and fermentable substrates impose selective pressures on gut microbial communities and their metabolisms. We evaluated the relative contributions of pH, alkalinity, and substrate on microbial community structure, metabolism, and functional interactions using triplicate batch cultures started from fecal slurry and incubated with an initial pH of 6.0, 6.5, or

pH and fermentable substrates impose selective pressures on gut microbial communities and their metabolisms. We evaluated the relative contributions of pH, alkalinity, and substrate on microbial community structure, metabolism, and functional interactions using triplicate batch cultures started from fecal slurry and incubated with an initial pH of 6.0, 6.5, or 6.9 and 10 mM glucose, fructose, or cellobiose as the carbon substrate. We analyzed 16S rRNA gene sequences and fermentation products. Microbial diversity was driven by both pH and substrate type. Due to insufficient alkalinity, a drop in pH from 6.0 to ~4.5 clustered pH 6.0 cultures together and distant from pH 6.5 and 6.9 cultures, which experienced only small pH drops. Cellobiose yielded more acidity than alkalinity due to the amount of fermentable carbon, which moved cellobiose pH 6.5 cultures away from other pH 6.5 cultures. The impact of pH on microbial community structure was reflected by fermentative metabolism. Lactate accumulation occurred in pH 6.0 cultures, whereas propionate and acetate accumulations were observed in pH 6.5 and 6.9 cultures and independently from the type of substrate provided. Finally, pH had an impact on the interactions between lactate-producing and -consuming communities. Lactate-producing Streptococcus dominated pH 6.0 cultures, and acetate- and propionate-producing Veillonella, Bacteroides, and Escherichia dominated the cultures started at pH 6.5 and 6.9. Acid inhibition on lactate-consuming species led to lactate accumulation. Our results provide insights into pH-derived changes in fermenting microbiota and metabolisms in the human gut.
Created2017-05-03
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Description
A two-patch mathematical model of Dengue virus type 2 (DENV-2) that accounts for vectors’ vertical transmission and between patches human dispersal is introduced. Dispersal is modelled via a Lagrangian approach. A host-patch residence-times basic reproduction number is derived and conditions under which the disease dies out or persists are established.

A two-patch mathematical model of Dengue virus type 2 (DENV-2) that accounts for vectors’ vertical transmission and between patches human dispersal is introduced. Dispersal is modelled via a Lagrangian approach. A host-patch residence-times basic reproduction number is derived and conditions under which the disease dies out or persists are established. Analytical and numerical results highlight the role of hosts’ dispersal in mitigating or exacerbating disease dynamics. The framework is used to explore dengue dynamics using, as a starting point, the 2002 outbreak in the state of Colima, Mexico.
Created2016-08-05
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Description
Purpose: To evaluate a new method of measuring ocular exposure in the context of a natural blink pattern through analysis of the variables tear film breakup time (TFBUT), interblink interval (IBI), and tear film breakup area (BUA).
Methods: The traditional methodology (Forced-Stare [FS]) measures TFBUT and IBI separately. TFBUT is measured

Purpose: To evaluate a new method of measuring ocular exposure in the context of a natural blink pattern through analysis of the variables tear film breakup time (TFBUT), interblink interval (IBI), and tear film breakup area (BUA).
Methods: The traditional methodology (Forced-Stare [FS]) measures TFBUT and IBI separately. TFBUT is measured under forced-stare conditions by an examiner using a stopwatch, while IBI is measured as the subject watches television. The new methodology (video capture manual analysis [VCMA]) involves retrospective analysis of video data of fluorescein-stained eyes taken through a slit lamp while the subject watches television, and provides TFBUT and BUA for each IBI during the 1-minute video under natural blink conditions. The FS and VCMA methods were directly compared in the same set of dry-eye subjects. The VCMA method was evaluated for the ability to discriminate between dry-eye subjects and normal subjects. The VCMA method was further evaluated in the dry eye subjects for the ability to detect a treatment effect before, and 10 minutes after, bilateral instillation of an artificial tear solution.
Results: Ten normal subjects and 17 dry-eye subjects were studied. In the dry-eye subjects, the two methods differed with respect to mean TFBUTs (5.82 seconds, FS; 3.98 seconds, VCMA; P = 0.002). The FS variables alone (TFBUT, IBI) were not able to successfully distinguish between the dry-eye and normal subjects, whereas the additional VCMA variables, both derived and observed (BUA, BUA/IBI, breakup rate), were able to successfully distinguish between the dry-eye and normal subjects in a statistically significant fashion. TFBUT (P = 0.034) and BUA/IBI (P = 0.001) were able to distinguish the treatment effect of artificial tears in dry-eye subjects.
Conclusion: The VCMA methodology provides a clinically relevant analysis of tear film stability measured in the context of a natural blink pattern.
Created2011-09-21
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Description
Purpose: To investigate use of an improved ocular tear film analysis protocol (OPI 2.0) in the Controlled Adverse Environment (CAE[superscript SM]) model of dry eye disease, and to examine the utility of new metrics in the identification of subpopulations of dry eye patients.
Methods: Thirty-three dry eye subjects completed a single-center,

Purpose: To investigate use of an improved ocular tear film analysis protocol (OPI 2.0) in the Controlled Adverse Environment (CAE[superscript SM]) model of dry eye disease, and to examine the utility of new metrics in the identification of subpopulations of dry eye patients.
Methods: Thirty-three dry eye subjects completed a single-center, single-visit, pilot CAE study. The primary endpoint was mean break-up area (MBA) as assessed by the OPI 2.0 system. Secondary endpoints included corneal fluorescein staining, tear film break-up time, and OPI 2.0 system measurements. Subjects were also asked to rate their ocular discomfort throughout the CAE. Dry eye endpoints were measured at baseline, immediately following a 90-minute CAE exposure, and again 30 minutes after exposure.
Results: The post-CAE measurements of MBA showed a statistically significant decrease from the baseline measurements. The decrease was relatively specific to those patients with moderate to severe dry eye, as measured by baseline MBA. Secondary endpoints including palpebral fissure size, corneal staining, and redness, also showed significant changes when pre- and post-CAE measurements were compared. A correlation analysis identified specific associations between MBA, blink rate, and palpebral fissure size. Comparison of MBA responses allowed us to identify subpopulations of subjects who exhibited different compensatory mechanisms in response to CAE challenge. Of note, none of the measures of tear film break-up time showed statistically significant changes or correlations in pre-, versus post-CAE measures.
Conclusion: This pilot study confirms that the tear film metric MBA can detect changes in the ocular surface induced by a CAE, and that these changes are correlated with other, established measures of dry eye disease. The observed decrease in MBA following CAE exposure demonstrates that compensatory mechanisms are initiated during the CAE exposure, and that this compensation may provide the means to identify and characterize clinically relevant subpopulations of dry eye patients.
Created2012-11-12
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Description
Diamond is considered as an ideal material for high field and high power devices due to its high breakdown field, high lightly doped carrier mobility, and high thermal conductivity. The modeling and simulation of diamond devices are therefore important to predict the performances of diamond based devices. In this context,

Diamond is considered as an ideal material for high field and high power devices due to its high breakdown field, high lightly doped carrier mobility, and high thermal conductivity. The modeling and simulation of diamond devices are therefore important to predict the performances of diamond based devices. In this context, we use Silvaco[superscript ®] Atlas, a drift-diffusion based commercial software, to model diamond based power devices. The models used in Atlas were modified to account for both variable range and nearest neighbor hopping transport in the impurity bands associated with high activation energies for boron doped and phosphorus doped diamond. The models were fit to experimentally reported resistivity data over a wide range of doping concentrations and temperatures. We compare to recent data on depleted diamond Schottky PIN diodes demonstrating low turn-on voltages and high reverse breakdown voltages, which could be useful for high power rectifying applications due to the low turn-on voltage enabling high forward current densities. Three dimensional simulations of the depleted Schottky PIN diamond devices were performed and the results are verified with experimental data at different operating temperatures.
Created2016-06-08
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Description
Recent efforts have attempted to describe the population structure of common chimpanzee, focusing on four subspecies: Pan troglodytes verus, P. t. ellioti, P. t. troglodytes, and P. t. schweinfurthii. However, few studies have pursued the effects of natural selection in shaping their response to pathogens and reproduction. Whey acidic protein

Recent efforts have attempted to describe the population structure of common chimpanzee, focusing on four subspecies: Pan troglodytes verus, P. t. ellioti, P. t. troglodytes, and P. t. schweinfurthii. However, few studies have pursued the effects of natural selection in shaping their response to pathogens and reproduction. Whey acidic protein (WAP) four-disulfide core domain (WFDC) genes and neighboring semenogelin (SEMG) genes encode proteins with combined roles in immunity and fertility. They display a strikingly high rate of amino acid replacement (dN/dS), indicative of adaptive pressures during primate evolution. In human populations, three signals of selection at the WFDC locus were described, possibly influencing the proteolytic profile and antimicrobial activities of the male reproductive tract. To evaluate the patterns of genomic variation and selection at the WFDC locus in chimpanzees, we sequenced 17 WFDC genes and 47 autosomal pseudogenes in 68 chimpanzees (15 P. t. troglodytes, 22 P. t. verus, and 31 P. t. ellioti). We found a clear differentiation of P. t. verus and estimated the divergence of P. t. troglodytes and P. t. ellioti subspecies in 0.173 Myr; further, at the WFDC locus we identified a signature of strong selective constraints common to the three subspecies in WFDC6—a recent paralog of the epididymal protease inhibitor EPPIN. Overall, chimpanzees and humans do not display similar footprints of selection across the WFDC locus, possibly due to different selective pressures between the two species related to immune response and reproductive biology.
Created2013-12-19
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Description
Electricity plays a special role in our lives and life. The dynamics of electrons allow light to flow through a vacuum. The equations of electron dynamics are nearly exact and apply from nuclear particles to stars. These Maxwell equations include a special term, the displacement current (of a vacuum). The

Electricity plays a special role in our lives and life. The dynamics of electrons allow light to flow through a vacuum. The equations of electron dynamics are nearly exact and apply from nuclear particles to stars. These Maxwell equations include a special term, the displacement current (of a vacuum). The displacement current allows electrical signals to propagate through space. Displacement current guarantees that current is exactly conserved from inside atoms to between stars, as long as current is defined as the entire source of the curl of the magnetic field, as Maxwell did.We show that the Bohm formulation of quantum mechanics allows the easy definition of the total current, and its conservation, without the dificulties implicit in the orthodox quantum theory. The orthodox theory neglects the reality of magnitudes, like the currents, during times that they are not being explicitly measured.We show how conservation of current can be derived without mention of the polarization or dielectric properties of matter. We point out that displacement current is handled correctly in electrical engineering by ‘stray capacitances’, although it is rarely discussed explicitly. Matter does not behave as physicists of the 1800’s thought it did. They could only measure on a time scale of seconds and tried to explain dielectric properties and polarization with a single dielectric constant, a real positive number independent of everything. Matter and thus charge moves in enormously complicated ways that cannot be described by a single dielectric constant,when studied on time scales important today for electronic technology and molecular biology. When classical theories could not explain complex charge movements, constants in equations were allowed to vary in solutions of those equations, in a way not justified by mathematics, with predictable consequences. Life occurs in ionic solutions where charge is moved by forces not mentioned or described in the Maxwell equations, like convection and diffusion. These movements and forces produce crucial currents that cannot be described as classical conduction or classical polarization. Derivations of conservation of current involve oversimplified treatments of dielectrics and polarization in nearly every textbook. Because real dielectrics do not behave in that simple way-not even approximately-classical derivations of conservation of current are often distrusted or even ignored. We show that current is conserved inside atoms. We show that current is conserved exactly in any material no matter how complex are the properties of dielectric, polarization, or conduction currents. Electricity has a special role because conservation of current is a universal law.Most models of chemical reactions do not conserve current and need to be changed to do so. On the macroscopic scale of life, conservation of current necessarily links far spread boundaries to each other, correlating inputs and outputs, and thereby creating devices.We suspect that correlations created by displacement current link all scales and allow atoms to control the machines and organisms of life. Conservation of current has a special role in our lives and life, as well as in physics. We believe models, simulations, and computations should conserve current on all scales, as accurately as possible, because physics conserves current that way. We believe models will be much more successful if they conserve current at every level of resolution, the way physics does.We surely need successful models as we try to control macroscopic functions by atomic interventions, in technology, life, and medicine. Maxwell’s displacement current lets us see stars. We hope it will help us see how atoms control life.
Created2017-10-28