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Some remarks on L¹ embeddings in the subelliptic setting
Get PDFIn this paper we establish an optimal Lorentz estimate for the Riesz potential in
the L¹ regime in the setting of a stratified group G: Let Q ≥ 2 be the homogeneous dimension of G and [Formula: see text] denote the Riesz potential of order α on G. Then, for every α∈(0,Q), there exists a constant C = C(α,Q) > 0 such that
[Formula: see text]
for all [Formula: see text] such that [Formula: see text], where X denotes the horizontal gradient.journal articl
Loss of β-cell identity and diabetic phenotype in mice caused by disruption of CNOT3-dependent mRNA deadenylation
Get PDFPancreatic β-cells are responsible for production and secretion of insulin in response to increasing blood glucose levels. Defects in β-cell function lead to hyperglycemia and diabetes mellitus. Here, we show that CNOT3, a CCR4-NOT deadenylase complex subunit, is dysregulated in islets in diabetic db/db mice, and that it is essential for murine β cell maturation and identity. Mice with β cell-specific Cnot3 deletion (Cnot3βKO) exhibit impaired glucose tolerance, decreased β cell mass, and they gradually develop diabetes. Cnot3βKO islets display decreased expression of key regulators of β cell maturation and function. Moreover, they show an increase of progenitor cell markers, β cell-disallowed genes, and genes relevant to altered β cell function. Cnot3βKO islets exhibit altered deadenylation and increased mRNA stability, partly accounting for the increased expression of those genes. Together, these data reveal that CNOT3-mediated mRNA deadenylation and decay constitute previously unsuspected post-transcriptional mechanisms essential for β cell identity.journal articl
Higher-spin holography in de Sitter space: horizon modes, black holes, and the boundary partition function
Get PDFOkinawa Institute of Science and Technology Graduate UniversityDoctor of PhilosophyHigher-spin holographic realizations of quantum gravity on de Sitter spacetimes is a promising model for addressing quantum gravity in an universe with positive cosmological constant. In this body of work we focus on issues related to (i) cosmological horizon modes, (ii) higher-spin black hole worldlines, and (iii) the boundary partition function. (i) We introduce a spinor-helicity formalism to encode the data of massless fields of arbitrary spin on a cosmological horizon. The evolution of free fields between past and future horizons reduces to a simple Fourier transform in terms of these variables. We show how this arises, by decomposing the problem into a pair of horizon-to-twistor problems. (ii) We decompose the boundary partition function Z in terms of spherical modes in the spinor-helicity basis. Even though the correlators agree, we observe a persistent discrepancy between the higher-spin-algebraic calculation of Z and the result of a direct CFT calculation. This suggests a failure of locality in higher-spin theory, even on the boundary. (iii) We show that the linearized version of the Didenko–Vasiliev black hole solves the Fronsdal field equations with a particle-like source. These fields are precisely the linearized bulk higher-spin fields corresponding to a bilocal source on the boundary. We show that the boundary correlator of two bilocal operators agrees with the bulk action describing the corresponding particles interacting in the bulk
Machine-driven parameter screen of biochemical reactions
Get PDFThe development of complex methods in molecular biology is a laborious, costly, iterative and often intuition-bound process where optima are sought in a multidimensional parameter space through step-by-step optimizations. The difficulty of miniaturizing reactions under the microliter volumes usually handled in multiwell plates by robots, plus the cost of the experiments, limit the number of parameters and the dynamic ranges that can be explored. Nevertheless, because of non-linearities of the response of biochemical systems to their reagent concentrations, broad dynamic ranges are necessary. Here we use a high-performance nanoliter handling platform and computer generation of liquid transfer programs to explore in quadruplicates 648 combinations of 4 parameters of a biochemical reaction, the reverse-transcription, which lead us to uncover non-linear responses, parameter interactions and novel mechanistic insights. With the increased availability of computer-driven laboratory platforms for biotechnology, our results demonstrate the feasibility and advantage of methods development based on reproducible, computer-aided exhaustive characterization of biochemical systems.journal articl
The effect of serotonin receptor 5-HT1B on lateral inhibition between spiny projection neurons in the mouse striatum
Get PDFOkinawa Institute of Science and Technology Graduate UniversityDoctor of PhilosophyStriatal spiny projection neurons (SPNs) make inhibitory synaptic connections with each other via local collaterals of their main axon, forming a local lateral inhibition network. Previous studies have shown that serotonin, acting via the 5-HT1B receptor, modulates neurotransmitter release from terminals in the target nuclei of SPN projections. Despite this established function, the role of 5-HT1B receptors in lateral inhibition among SPNs remains poorly understood. Spiny neuron activity ultimately underlies basal ganglia functions and knowledge of striatal circuit activity is critical for approaching disorders like Parkinson’s disease. In this thesis, I investigated the role of the 5-HT1B receptor in modulation of lateral inhibition in the striatum. To address this issue, whole-cell patch clamp recordings were made from SPNs in acute mouse brain slices, while optically stimulating presynaptic SPNs expressing channelrhodopsin. Inhibitory postsynaptic currents (IPSCs) mediated by GABA were measured before and after application of a 5-HT1B receptor agonist. Activation of 5-HT1B receptors significantly reduced the amplitude of IPSCs in SPNs for both, direct and indirect pathway neurons. This was blocked by application of a 5-HT1B antagonist. Further analysis suggested that the effect was due to a reduced probability of presynaptic release of GABA rather than a change in quantal size. Collectively, these results show a prominent role of serotonin in modulating lateral inhibition among striatal neurons, extending existing knowledge of its role in basal ganglia function. The 5-HT1B receptor may, therefore, be a suitable target for future behavioral experiments investigating the currently unknown role of lateral inhibition in the function of the striatum.doctoral thesi
Tree of motility – A proposed history of motility systems in the tree of life
Get PDFMotility often plays a decisive role in the survival of species. Five systems of motility have been studied in depth: those propelled by bacterial flagella, eukaryotic actin polymerization and the eukaryotic motor proteins myosin, kinesin and dynein. However, many organisms exhibit surprisingly diverse motilities, and advances in genomics, molecular biology and imaging have showed that those motilities have inherently independent mechanisms. This makes defining the breadth of motility nontrivial, because novel motilities may be driven by unknown mechanisms. Here, we classify the known motilities based on the unique classes of movement-producing protein architectures. Based on this criterion, the current total of independent motility systems stands at 18 types. In this perspective, we discuss these modes of motility relative to the latest phylogenetic Tree of Life and propose a history of motility. During the ~4 billion years since the emergence of life, motility arose in Bacteria with flagella and pili, and in Archaea with archaella. Newer modes of motility became possible in Eukarya with changes to the cell envelope. Presence or absence of a peptidoglycan layer, the acquisition of robust membrane dynamics, the enlargement of cells and environmental opportunities likely provided the context for the (co)evolution of novel types of motility.journal articl
Are you what you eat? A highly transient and prey‐influenced gut microbiome in the grey house spider Badumna longinqua
Get PDFStable core microbial communities have been described in numerous animal species and are commonly associated with fitness benefits for their hosts. Recent research, however, highlights examples of species whose microbiota are transient and environmentally derived. Here, we test the effect of diet on gut microbial community assembly in the spider Badumna longinqua. Using 16S rRNA gene amplicon sequencing combined with quantitative PCR, we analyzed diversity and abundance of the spider's gut microbes, and simultaneously characterized its prey communities using nuclear rRNA markers. We found a clear correlation between community similarity of the spider's insect prey and gut microbial DNA, suggesting that microbiome assembly is primarily diet-driven. This assumption is supported by a feeding experiment, in which two types of prey-crickets and fruit flies-both substantially altered microbial diversity and community similarity between spiders, but did so in different ways. After cricket consumption, numerous cricket-derived microbes appeared in the spider's gut, resulting in a rapid homogenization of microbial communities among spiders. In contrast, few prey-associated bacteria were detected after consumption of fruit flies; instead, the microbial community was remodelled by environmentally sourced microbes, or abundance shifts of rare taxa in the spider's gut. The reshaping of the microbiota by both prey taxa mimicked a stable core microbiome in the spiders for several weeks post feeding. Our results suggest that the spider's gut microbiome undergoes pronounced temporal fluctuations, that its assembly is dictated by the consumed prey, and that different prey taxa may remodel the microbiota in drastically different ways.journal articl
Unidirectional Charge Transport via Ripplonic Polarons in a Three-Terminal Microchannel Device
Get PDFWe study the transport of surface electrons on superfluid helium through a microchannel structure in which the charge flow splits into two branches, one flowing straight and one turned at 90°. According to Ohm’s law, an equal number of charges should flow into each branch. However, when the electrons are dressed by surface excitations (ripplons) to form polaronlike particles with sufficiently large effective mass, all the charge follows the straight path due to momentum conservation. This surface-wave induced transport is analogous to the motion of electrons coupled to surface acoustic waves in semiconductor 2DEGs.journal articl
High scale validity of the DFSZ axion model with precision
Get PDFWith the assumption of classical scale invariance at the Planck scale, the DFSZ axion model can generate the Higgs mass terms of the appropriate size through technically natural parameters and may be valid up to the Planck scale. We discuss the high scale validity of the Higgs sector, namely the absence of Landau poles and the vacuum stability. The Higgs sector is identical to that of the type-II two Higgs doublet model with a limited number of the Higgs quartic couplings. We utilize the state-of-the-art method to calculate vacuum decay rates and find that they are enhanced at most by 1010 compared with the tree level evaluation. We also discuss the constraints from flavor observables, perturbative unitarity, oblique parameters and collider searches. We find that the high scale validity tightly constrains the parameter region, but there is still a chance to observe at most about 10% deviation of the 125 GeV Higgs couplings to the fermions.journal articl
Boundary curvature effect on the wrinkling of thin suspended films
Get PDFA relation between the boundary curvature κ and the wrinkle wavelength λ of a thin suspended film under boundary confinement is demonstrated. Experiments were performed with nanocrystalline diamond films of approximate thickness 184nm grown on glass substrates. By removing portions of the substrates after growth, suspended films with circular boundaries of radius 30–811 μm were fabricated. Due to residual stresses, the portions of the film bonded to the substrate are of approximate compressive prestrain 11×10⁻⁴ and the suspended portions of the film are azimuthally wrinkled at their boundary. Measurements show that λ decreases monotonically with κ, and a simple model that is in line with this trend is proposed. The model can be applied to design devices with functional wrinkles and can be adapted to gain insight into other systems such as plant leaves. A method for measuring residual compressive strain in thin films, which complements standard strain characterization methods, is also described.journal articl