The Collaborative Cross Consortium reports here on the development of a unique genetic resource population. The Collaborative Cross (CC) is a multiparental recombinant inbred panel derived from eight laboratory mouse inbred strains. Breeding of the CC lines was initiated at multiple international sites using mice from The Jackson Laboratory. Currently, this innovative project is breeding independent CC lines at the University of North Carolina (UNC), at Tel Aviv University (TAU), and at Geniad in Western Australia (GND). These institutions aim to make publicly available the completed CC lines and their genotypes and sequence information. We genotyped, and report here, results from 458 extant lines from UNC, TAU, and GND using a custom genotyping array with 7500 SNPs designed to be maximally informative in the CC and used a novel algorithm to infer inherited haplotypes directly from hybridization intensity patterns. We identified lines with breeding errors and cousin lines generated by splitting incipient lines into two or more cousin lines at early generations of inbreeding. We then characterized the genome architecture of 350 genetically independent CC lines. Results showed that founder haplotypes are inherited at the expected frequency, although we also consistently observed highly significant transmission ratio distortion at specific loci across all three populations. On chromosome 2, there is significant overrepresentation of WSB/EiJ alleles, and on chromosome X, there is a large deficit of CC lines with CAST/EiJ alleles. Linkage disequilibrium decays as expected and we saw no evidence of gametic disequilibrium in the CC population as a whole or in random subsets of the population. Gametic equilibrium in the CC population is in marked contrast to the gametic disequilibrium present in a large panel of classical inbred strains. Finally, we discuss access to the CC population and to the associated raw data describing the genetic structure of individual lines. Integration of rich phenotypic and genomic data over time and across a wide variety of fields will be vital to delivering on one of the key attributes of the CC, a common genetic reference platform for identifying causative variants and genetic networks determining traits in mammals.
Complex human traits are influenced by variation in regulatory DNA through mechanisms that are not fully understood. Since regulatory elements are conserved between humans and mice, a thorough annotation of cis regulatory variants in mice could aid in this process. Here we provide a detailed portrait of mouse gene expression across multiple tissues in a three-way diallel. Greater than 80% of mouse genes have cis regulatory variation. These effects influence complex traits and usually extend to the human ortholog. Further, we estimate that at least one in every thousand SNPs creates a cis regulatory effect. We also observe two types of parent-of-origin effects, including classical imprinting and a novel, global allelic imbalance in favor of the paternal allele. We conclude that, as with humans, pervasive regulatory variation influences complex genetic traits in mice and provide a new resource toward understanding the genetic control of transcription in mammals.
Over the past two decades, solar- and astrophysicists and material scientists have been researching and developing new-generation semiconductor-based vacuum ultraviolet (VUV) detectors with low power consumption and small size for replacing traditional heavy and high-energy-consuming microchannel-detection systems, to study the formation and evolution of stars. However, the most desirable semiconductor-based VUV photovoltaic detector capable of achieving zero power consumption has not yet been achieved. With high-crystallinity multistep epitaxial grown AlN as a VUV-absorbing layer for photogenerated carriers and p-type graphene (with unexpected VUV transmittance >96%) as a transparent electrode to collect excited holes, we constructed a heterojunction device with photovoltaic detection for VUV light. The device exhibits an encouraging VUV photoresponse, high external quantum efficiency (EQE) and extremely fast tempera response (80 ns, 10-10 times faster than that of the currently reported VUV photoconductive devices). This work has provided an idea for developing zero power consumption and integrated VUV photovoltaic detectors with ultrafast and high-sensitivity VUV detection capability, which not only allows future spacecraft to operate with longer service time and lower launching cost but also ensures an ultrafast evolution of interstellar objects.
Vigorous sperm motility, including the transition from progressive to hyperactivated motility that occurs in the female reproductive tract, is required for normal fertilization in mammals. We developed an automated, quantitative method that objectively classifies five distinct motility patterns of mouse sperm using Support Vector Machines (SVM), a common method in supervised machine learning. This multiclass SVM model is based on more than 2000 sperm tracks that were captured by computer-assisted sperm analysis (CASA) during in vitro capacitation and visually classified as progressive, intermediate, hyperactivated, slow, or weakly motile. Parameters associated with the classified tracks were incorporated into established SVM algorithms to generate a series of equations. These equations were integrated into a binary decision tree that sequentially sorts uncharacterized tracks into distinct categories. The first equation sorts CASA tracks into vigorous and nonvigorous categories. Additional equations classify vigorous tracks as progressive, intermediate, or hyperactivated and nonvigorous tracks as slow or weakly motile. Our CASAnova software uses these SVM equations to classify individual sperm motility patterns automatically. Comparisons of motility profiles from sperm incubated with and without bicarbonate confirmed the ability of the model to distinguish hyperactivated patterns of motility that develop during in vitro capacitation. The model accurately classifies motility profiles of sperm from a mutant mouse model with severe motility defects. Application of the model to sperm from multiple inbred strains reveals strain-dependent differences in sperm motility profiles. CASAnova provides a rapid and reproducible platform for quantitative comparisons of motility in large, heterogeneous populations of mouse sperm.
Solar-blind ultraviolet (SBUV) detection has important applications in wireless secure communication, early warning, and so forth. However, the desired key device for SBUV detection and high-sensitivity and low-noise "sandwich" photodetector with large detective area is difficult to be fabricated because it is usually hard for traditional wide band gap semiconductors to boast both high conductivity and high SBUV transparency. Here, we proposed to use graphene as the transparent conductive layer to form graphene/β-GaO heterojunction. With the help of large-area graphene and hot carrier multiplication, a SBUV photodetector with large detective area, low dark current, and high sensitivity was successfully assembled. Its photoresponsivity is 1-3 orders of magnitude higher than that of the conventional SBUV photodetectors, and its response speed can rival the best device ever reported.
In the present work, we develop a highly accurate, fifteen-dimensional potential energy surface (PES) of CH4 interacting on a rigid flat Ni(111) surface with the methodology of neural network (NN) fit to a database consisted of about 194 208 ab initio density functional theory (DFT) energy points. Some careful tests of the accuracy of the fitting PES are given through the descriptions of the fitting quality, vibrational spectrum of CH4 in vacuum, transition state (TS) geometries as well as the activation barriers. Using a 25-60-60-1 NN structure, we obtain one of the best PESs with the least root mean square errors: 10.11 meV for the entrance region and 17.00 meV for the interaction and product regions. Our PES can reproduce the DFT results very well in particular for the important TS structures. Furthermore, we present the sticking probability S0 of ground state CH4 at the experimental surface temperature using some sudden approximations by Jackson's group. An in-depth explanation is given for the underestimated sticking probability.
Millimeter-sized Cs4PbBr6 bulk single crystal that has no green luminescence was successfully grown from concentrated CsBr aqueous solution for the first time. Absorption spectrum indicates an optical absorption starting from 3.6 eV and a localized absorption in the range of 3.8–4.2 eV. Photoluminescence spectrum clearly shows that the crystal has no green emission. Along with the calculated electronic band structure, it is concluded that Cs4PbBr6 has a wide bandgap of 3.6 eV. Through vacuum annealing treatment, the green luminescence of the original nongreen-luminescent Cs4PbBr6 crystal was successfully activated, which is possibly due to the formation of CsPbBr3. This work gives the method to obtain millimeter-sized Cs4PbBr6 crystals from aqueous solution and suggests a route to activate its green luminescence. The results are significant for the deep understanding of the intrinsic properties and exploring the potential applications of wide bandgap Cs4PbBr6.
The Polanyi rules, which state that vibrational energy is more efficient in promoting a late-barrier reaction than translational energy, were questioned recently by an experimental unexpected finding that the CH stretch excitation is no more effective in promoting the late-barrier Cl + CHD 3 reaction than the translational energy. However, the present quantum dynamics study on the best-available potential energy surface for the title reaction reveals that the CH stretch excitation does promote the reaction significantly, except at low collision energies. Further studies should be carried out to solve the disagreements between theory and experiment on the reaction. SECTION: Kinetics and DynamicsI n a typical chemical reaction with an energetic barrier, there is a saddle point that the reactants must surmount to reach the product side. Which form of energy initially deposited in reactants, translational or vibrational, is more efficacious in surmounting the barrier is one of the central topics in the field of reaction dynamics. In 1972, on the basis of theoretical studies of some model atom−diatom reactions, Polanyi proposed the well-known Polanyi rules, which state that vibrational energy is more efficient in promoting a late-barrier reaction (that is, a transition state resembling the products) than translational energy, whereas the reverse is true for an early barrier reaction.1 Over the past decades, the rules have enjoyed great successes not only on the atom−diatom reactions 2,3 but also on the H and Cl + H 2 O reactions and their isotope analogues. 4−9However, the generality of these rules for the Cl + CH 4 reaction was questioned recently by an unexpected experimental finding on the title reaction.10 Following the early work, carried out in the groups of Crim, 11 Zare, 12 and Orr-Ewing, 13Liu and co-workers performed crossed molecular beam experiments on the title reaction with the CH vibration in the ground and first stretch vibrational excited states and measured integral and differential cross sections for product CD 3 in the ground vibrational state (CD 3 (ν = 0)). They found that at the same total energy, the integral cross section for CD 3 (ν = 0) for the initial CH stretch excited state, σ s (ν = 0), is smaller than that at low collision energies and becomes comparable at higher collision energies to the corresponding one for the ground initial state, σ g (ν = 0). On the basis of their estimation that the CD 3 (ν = 0) product accounts for 2/3 of the total product distribution for the initial CH excited state, they concluded that the CH stretch excitation is no more effective 10 or slightly more effective 14 in promoting the late-barrier Cl + CHD 3 reaction than an equivalent amount of translational energy, in contradiction with the Polanyi rules. Equally interesting, the same group also found that the CH stretch excitation inhibits CH bond cleavage in the early-barrier F + CHD 3 reaction. 15To study the reaction theoretically, Czakóand Bowman recently developed a high-quality, full-dimensi...
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