Transcriptome-wide analysis reveals different categories of response to a standardised immune challenge in a wild rodent

Individuals vary in their immune response and, as a result, some are more susceptible to infectious disease than others. Little is known about the nature of this individual variation in natural populations, or which components of immune pathways are most responsible, but defining this underlying landscape of variation is an essential first step to understanding the drivers of this variation and, ultimately, predicting the outcome of infection. We describe transcriptome-wide variation in response to a standardised immune challenge in wild field voles. We find that markers can be categorised into a limited number of types. For the majority of markers, the response of an individual is dependent on its baseline expression level, with significant enrichment in this category for conventional immune pathways. Another, moderately sized, category contains markers for which the responses of different individuals are also variable but independent of their baseline expression levels. This category lacks any enrichment for conventional immune pathways. We further identify markers which display particularly high individual variability in response, and could be used as markers of immune response in larger studies. Our work shows how a standardised challenge performed on a natural population can reveal the patterns of natural variation in immune response

Accurate quadratic-response approximation for the self-consistent pseudopotential of semiconductor nanostructures

Quadratic-response theory is shown to provide a conceptually simple but accurate approximation for the self-consistent one-electron potential of semiconductor nanostructures. Numerical examples are presented for GaAs/AlAs and InGaAs/InP (001) superlattices using the local-density approximation to density-functional theory and norm-conserving pseudopotentials without spin-orbit coupling. When the reference crystal is chosen to be the virtual-crystal average of the two bulk constituents, the absolute error in the quadratic-response potential for Gamma(15) valence electrons is about 2 meV for GaAs/AlAs and 5 meV for InGaAs/InP. Low-order multipole expansions of the electron density and potential response are shown to be accurate throughout a small neighborhood of each reciprocal lattice vector, thus providing a further simplification that is confirmed to be valid for slowly varying envelope functions. Although the linear response is about an order of magnitude larger than the quadratic response, the quadratic terms are important both quantitatively (if an accuracy of better than a few tens of meV is desired) and qualitatively (due to their different symmetry and long-range dipole effects).Comment: 16 pages, 20 figures; v2: new section on limitations of theor

Superoxide Signaling in Perivascular Adipose Tissue Promotes Age-Related Artery Stiffness

We tested the hypothesis that superoxide signaling within aortic perivascular adipose tissue (PVAT) contributes to large elastic artery stiffening in old mice. Young (4-6 months), old (26-28 months), and old treated with 4-Hydroxy-2,2,6,6-tetramethylpiperidine 1-oxyl (TEMPOL), a superoxide scavenger (1 mm in drinking water for 3 weeks), male C57BL6/N mice were studied. Compared with young, old had greater large artery stiffness assessed by aortic pulse wave velocity (aPWV, 436 ± 9 vs. 344 ± 5 cm s(-1)) and intrinsic mechanical testing (3821 ± 427 vs. 1925 ± 271 kPa) (both P \u3c 0.05). TEMPOL treatment in old reversed both measures of arterial stiffness. Aortic PVAT superoxide production was greater in old (P \u3c 0.05 vs. Y), which was normalized with TEMPOL. Compared with young, old controls had greater pro-inflammatory proteins in PVAT-conditioned media (P \u3c 0.05). Young recipient mice transplanted with PVAT from old compared with young donors for 8 weeks had greater aPWV (409 ± 7 vs. 342 ± 8 cm s(-1)) and intrinsic mechanical properties (3197 ± 647 vs. 1889 ± 520 kPa) (both P \u3c 0.05), which was abolished with TEMPOL supplementation in old donors. Tissue-cultured aortic segments from old in the presence of PVAT had greater mechanical stiffening compared with old cultured in the absence of PVAT and old with PVAT and TEMPOL (both, P \u3c 0.05). In addition, PVAT-derived superoxide was associated with arterial wall hypertrophy and greater adventitial collagen I expression with aging that was attenuated by TEMPOL. Aging or TEMPOL treatment did not affect blood pressure. Our findings provide evidence for greater age-related superoxide production and pro-inflammatory proteins in PVAT, and directly link superoxide signaling in PVAT to large elastic artery stiffness

A candidate tolerance gene identified in a natural population of field voles (Microtus agrestis)

The animal immune response has hitherto been viewed primarily in the context of resistance only. However, individuals, can also employ a tolerance strategy to maintain good health in the face of on-going infection. To shed light on the genetic and physiological basis of tolerance, we use a natural population of field voles, Microtus agrestis, to search for an association between the expression of the transcription factor Gata3, previously identified as a marker of tolerance in this system, and polymorphism in 84 immune and non-immune genes. Our results show clear evidence for an association between Gata3 expression and polymorphism in the Fcer1a gene, with the explanatory power of this polymorphism being comparable to that of other non-genetic variables previously identified as important predictors of Gata3 expression. We also uncover the possible mechanism behind this association using an existing protein-protein interaction network for the mouse model rodent, Mus musculus, which we validate using our own expression network for M. agrestis. Our results suggest that the polymorphism in question may be working at the transcriptional level, leading to changes in the expression of the Th2-related genes, Tyrosine-protein kinase BTK and Tyrosine-protein kinase TXK, and hence potentially altering the strength of the Th2 response, of which Gata3 is a mediator. We believe our work has implications for both treatment and control of infectious disease

The IPAC Image Subtraction and Discovery Pipeline for the intermediate Palomar Transient Factory

We describe the near real-time transient-source discovery engine for the intermediate Palomar Transient Factory (iPTF), currently in operations at the Infrared Processing and Analysis Center (IPAC), Caltech. We coin this system the IPAC/iPTF Discovery Engine (or IDE). We review the algorithms used for PSF-matching, image subtraction, detection, photometry, and machine-learned (ML) vetting of extracted transient candidates. We also review the performance of our ML classifier. For a limiting signal-to-noise ratio of 4 in relatively unconfused regions, "bogus" candidates from processing artifacts and imperfect image subtractions outnumber real transients by ~ 10:1. This can be considerably higher for image data with inaccurate astrometric and/or PSF-matching solutions. Despite this occasionally high contamination rate, the ML classifier is able to identify real transients with an efficiency (or completeness) of ~ 97% for a maximum tolerable false-positive rate of 1% when classifying raw candidates. All subtraction-image metrics, source features, ML probability-based real-bogus scores, contextual metadata from other surveys, and possible associations with known Solar System objects are stored in a relational database for retrieval by the various science working groups. We review our efforts in mitigating false-positives and our experience in optimizing the overall system in response to the multitude of science projects underway with iPTF.Comment: 66 pages, 21 figures, 7 tables, accepted by PAS

Observation of metastable states in spinor Bose-Einstein condensates

Bose-Einstein condensates have been prepared in long-lived metastable excited states. Two complementary types of metastable states were observed. The first is due to the immiscibility of multiple components in the condensate, and the second to local suppression of spin-relaxation collisions. Relaxation via re-condensation of non-condensed atoms, spin relaxation, and quantum tunneling was observed. These experiments were done with F=1 spinor Bose-Einstein condensates of sodium confined in an optical dipole trap.Comment: 3 figures included in paper, fourth figure separat

Thermodynamics of an interacting trapped Bose-Einstein gas in the classical field approximation

We present a convenient technique describing the condensate in dynamical equilibrium with the thermal cloud, at temperatures close to the critical one. We show that the whole isolated system may be viewed as a single classical field undergoing nonlinear dynamics leading to a steady state. In our procedure it is the observation process and the finite detection time that allow for splitting the system into the condensate and the thermal cloud.Comment: 4 pages, 4 eps figures, final versio