Surface plasmon resonance (SPR) biosensors prepared using optical fibers can be used as a cost-effective and relatively simple-to-implement alternative to well established biosensor platforms for ...monitoring biomolecular interactions in situ or possibly in vivo. The fiber biosensor presented in this study utilizes an in-fiber tilted Bragg grating to excite the SPR on the surface of the sensor over a large range of external medium refractive indices, with minimal cross-sensitivity to temperature and without compromising the structural integrity of the fiber. The label-free biorecognition scheme used demonstrates that the sensor relies on the functionalization of the gold-coated fiber with aptamers, synthetic DNA sequences that bind with high specificity to a given target. In addition to monitoring the functionalization of the fiber by the aptamers in real-time, the results also show how the fiber biosensor can detect the presence of the aptamer’s target, in various concentrations of thrombin in buffer and serum solutions. The findings also show how the SPR biosensor can be used to evaluate the dissociation constant (K d), as the binding constant agrees with values already reported in the literature.
Optical loss plays a significant role in optical experiments involving optical cavities such as recycling cavities and filter cavities in laser interferometer gravitational-wave detectors. For those ...cavities, modal frequency degeneracy, where the fundamental and a higher order mode resonate inside the cavity simultaneously, is a potential mechanism which may bring extra optical loss to the cavity thus degrade detection sensitivity. In this paper, we report observation of modal frequency degeneracy in a large-scale suspended Fabry-Pérot cavity. The cavity
g
-factor is tuned by a CO
2
laser heating one test mass, and the cavity finesse is obtained from a ring-down measurement of the transmitted light. We demonstrate that the modal frequency degeneracy can cause a reduction of the cavity finesse by up to ∼30%, corresponding to a ∼2-fold increase in total optical loss. To minimize optical loss in gravitational-wave detectors, the effect of modal frequency degeneracy needs to be taken into account in the design and operation of the detector.
The Origin of Lunar Mascon Basins Melosh, H. J.; Freed, Andrew M.; Johnson, Brandon C. ...
Science (American Association for the Advancement of Science),
06/2013, Letnik:
340, Številka:
6140
Journal Article
Recenzirano
Odprti dostop
High-resolution gravity data from the Gravity Recovery and Interior Laboratory spacecraft have clarified the origin of lunar mass concentrations (mascons). Free-air gravity anomalies over lunar ...impact basins display bull's-eye patterns consisting of a central positive (mascón) anomaly, a surrounding negative collar, and a positive outer annulus. We show that this pattern results from impact basin excavation and collapse followed by isostatic adjustment and cooling and contraction of a voluminous melt pool. We used a hydrocode to simulate the impact and a self-consistent finite-element model to simulate the subsequent viscoelastic relaxation and cooling. The primary parameters controlling the modeled gravity signatures of mascón basins are the impactor energy, the lunar thermal gradient at the time of impact, the crustal thickness, and the extent of volcanic fill.
Although countless highly penetrant variants have been associated with Mendelian disorders, the genetic etiologies underlying complex diseases remain largely unresolved. By mining the medical records ...of over 110 million patients, we examine the extent to which Mendelian variation contributes to complex disease risk. We detect thousands of associations between Mendelian and complex diseases, revealing a nondegenerate, phenotypic code that links each complex disorder to a unique collection of Mendelian loci. Using genome-wide association results, we demonstrate that common variants associated with complex diseases are enriched in the genes indicated by this “Mendelian code.” Finally, we detect hundreds of comorbidity associations among Mendelian disorders, and we use probabilistic genetic modeling to demonstrate that Mendelian variants likely contribute nonadditively to the risk for a subset of complex diseases. Overall, this study illustrates a complementary approach for mapping complex disease loci and provides unique predictions concerning the etiologies of specific diseases.
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•Analyzed over 100 million unique patient records from the United States and Denmark•Discovered a nondegenerate, Mendelian comorbidity code for complex diseases•Results predict genetic loci enriched with a spectrum of complex disease variants•Inferred widespread epistasis among loci that harbor deleterious Mendelian variants
By mining the medical records of over 110 million patients, thousands of previously unappreciated associations between Mendelian and complex diseases are detected.
We describe a mechanism of flagellar motor control by the bacterial signaling molecule c-di-GMP, which regulates several cellular behaviors. E. coli and Salmonella have multiple c-di-GMP cyclases and ...phosphodiesterases, yet absence of a specific phosphodiesterase YhjH impairs motility in both bacteria. yhjH mutants have elevated c-di-GMP levels and require YcgR, a c-di-GMP-binding protein, for motility inhibition. We demonstrate that YcgR interacts with the flagellar switch-complex proteins FliG and FliM, most strongly in the presence of c-di-GMP. This interaction reduces the efficiency of torque generation and induces CCW motor bias. We present a “backstop brake” model showing how both effects can result from disrupting the organization of the FliG C-terminal domain, which interacts with the stator protein MotA to generate torque. Inhibition of motility and chemotaxis may represent a strategy to prepare for sedentary existence by disfavoring migration away from a substrate on which a biofilm is to be formed.
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► c-di-GMP regulates the transition from motility to sessility in eubacteria ► In E. coli and Salmonella enterica, c-di-GMP forms a complex with YcgR ► The c-di-GMP/YcgR complex interacts with flagellar switch proteins FliM and FliG ► This interaction slows the motor and induces CCW rotation, inhibiting chemotaxis
T cell activation and function require a structured engagement of antigen-presenting cells. These cell contacts are characterized by two distinct dynamics in vivo: transient contacts resulting from ...promigratory junctions called immunological kinapses or prolonged contacts from stable junctions called immunological synapses. Kinapses operate in the steady state to allow referencing to self-peptide-MHC (pMHC) and searching for pathogen-derived pMHC. Synapses are induced by T cell receptor (TCR) interactions with agonist pMHC under specific conditions and correlate with robust immune responses that generate effector and memory T cells. High-resolution imaging has revealed that the synapse is highly coordinated, integrating cell adhesion, TCR recognition of pMHC complexes, and an array of activating and inhibitory ligands to promote or prevent T cell signaling. In this review, we examine the molecular components, geometry, and timing underlying kinapses and synapses. We integrate recent molecular and physiological data to provide a synthesis and suggest ways forward.
Clinical heterogeneity is common in Mendelian disease, but small sample sizes make it difficult to identify specific contributing factors. However, if a disease represents the severely affected ...extreme of a spectrum of phenotypic variation, then modifier effects may be apparent within a larger subset of the population. Analyses that take advantage of this full spectrum could have substantially increased power. To test this, we developed cryptic phenotype analysis, a model-based approach that infers quantitative traits that capture disease-related phenotypic variability using qualitative symptom data. By applying this approach to 50 Mendelian diseases in two cohorts, we identify traits that reliably quantify disease severity. We then conduct genome-wide association analyses for five of the inferred cryptic phenotypes, uncovering common variation that is predictive of Mendelian disease-related diagnoses and outcomes. Overall, this study highlights the utility of computationally-derived phenotypes and biobank-scale cohorts for investigating the complex genetic architecture of Mendelian diseases.
The mucopolysaccharidoses (MPSs) are a subset of lysosomal storage diseases caused by deficiencies in the enzymes required to metabolize glycosaminoglycans (GAGs), a group of extracellular ...heteropolysaccharides that play diverse roles in human physiology. As a result, GAGs accumulate in multiple tissues, and affected patients typically develop progressive, multi-systemic symptoms in early childhood. Over the last 30 years, the treatments available for the MPSs have evolved tremendously. There are now multiple therapies that delay the progression of these debilitating disorders, although their effectiveness varies according to MPS sub-type. In this review, we discuss the basic principle underlying MPS treatment (enzymatic “cross correction”), and we review the three general modalities currently available: hematopoietic stem cell transplantation, enzymatic replacement, and gene therapy. For each treatment type, we discuss its effectiveness across the MPS subtypes, its inherent risks, and future directions. Long term, we suspect that treatment for the MPSs will continue to evolve, and through a combination of early diagnosis and effective management, these patients will continue to live longer lives with improved outcomes for quality of life.
Tree ferns are an important structural component of forests in many countries. However, because their regeneration is often unrelated to major disturbances, their age is often difficult to determine. ...In addition, rates of growth may not be uniform, which further complicates attempts to determine their age. In this study, we measured 5 years of growth of Cyathea australis and Dicksonia antarctica after a large wildfire in 2009 in south-eastern Australia. We found growth rates of these two species were unaffected by aspect and elevation but slope had a minor effect with D. antarctica growing 0.3mm faster for each additional degree of slope. Geographic location influenced growth in both species by up to 12 - 14mm/yr. The most consistent factor influencing growth rate, however, was initial height at the time of the 2009 fire; a finding consistent in both species and all geographic locations. For both tree fern species, individuals that were taller at the commencement of the study had greater overall growth for the duration of the study. This effect did not decrease even among the tallest tree ferns in our study (up to 6 metres tall). Overall, Cyathea australis averaged 73 (± 22)mm/year of growth (± 1SD), with the rate increasing 5mm/yr per metre of additional height. Dicksonia antarctica averaged 33 (± 13)mm/year, increasing by 6mm/yr/m. Growth rates dependent on initial height were unexpected and we discuss possible reasons for this finding. Variable growth rates also suggest that common age estimation methods of dividing height by average growth rate are likely to underestimate the age of short tree ferns, while overestimating the age of tall tree ferns, particularly if they have been subject to a fire.
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