Cotunneling-mediated transport through excited states in the Coulomb blockade regime

We present finite bias transport measurements on a few-electron quantum dot. In the Coulomb blockade regime, strong signatures of inelastic cotunneling occur which can directly be assigned to excited states observed in the non-blockaded regime. In addition, we observe structures related to sequential tunneling through the dot, occuring after it has been excited by an inelastic cotunneling process. We explain our findings using transport calculations within the real-time Green's function approach, including diagrams up to fourth order in the tunneling matrix elements.Comment: 4 pages, 3 figure

Substrate-Assisted Catalysis Unifies Two Families of Chitinolytic Enzymes

Hen egg-white lysozyme has long been the paradigm for enzymatic glycosyl hydrolysis with retention of configuration, with a protonated carboxylic acid and a deprotonated carboxylate participating in general acid-base catalysis. In marked contrast, the retaining chitin degrading enzymes from glycosyl hydrolase families 18 and 20 all have a single glutamic acid as the catalytic acid but lack a nucleophile on the enzyme. Both families have a catalytic (βα)8-barrel domain in common. X-ray structures of three different chitinolytic enzymes complexed with substrates or inhibitors identify a retaining mechanism involving a protein acid and the carbonyl oxygen atom of the substrate’s C2 N-acetyl group as the nucleophile. These studies unambiguously demonstrate the distortion of the sugar ring toward a sofa conformation, long postulated as being close to that of the transition state in glycosyl hydrolysis.

Dual mechanism of brain injury and novel treatment strategy in maple syrup urine disease

Maple syrup urine disease (MSUD) is an inherited disorder of branched-chain amino acid metabolism presenting with lifethreatening cerebral oedema and dysmyelination in affected individuals. Treatment requires life-long dietary restriction and monitoring of branched-chain amino acids to avoid brain injury. Despite careful management, children commonly suffer metabolic decompensation in the context of catabolic stress associated with non-specific illness. The mechanisms underlying this decompensation and brain injury are poorly understood. Using recently developed mouse models of classic and intermediate maple syrup urine disease, we assessed biochemical, behavioural and neuropathological changes that occurred during encephalopathy in these mice. Here, we show that rapid brain leucine accumulation displaces other essential amino acids resulting in neurotransmitter depletion and disruption of normal brain growth and development. A novel approach of administering norleucine to heterozygous mothers of classic maple syrup urine disease pups reduced branched-chain amino acid accumulation in milk as well as blood and brain of these pups to enhance survival. Similarly, norleucine substantially delayed encephalopathy in intermediate maple syrup urine disease mice placed on a high protein diet that mimics the catabolic stress shown to cause encephalopathy in human maple syrup urine disease. Current findings suggest two converging mechanisms of brain injury in maple syrup urine disease including: (i) neurotransmitter deficiencies and growth restriction associated with branchedchain amino acid accumulation and (ii) energy deprivation through Krebs cycle disruption associated with branched-chain ketoacid accumulation. Both classic and intermediate models appear to be useful to study the mechanism of brain injury and potential treatment strategies for maple syrup urine disease. Norleucine should be further tested as a potential treatment to prevent encephalopathy in children with maple syrup urine disease during catabolic stress

Habitat structure: a fundamental concept and framework for urban soil ecology

Habitat structure is defined as the composition and arrangement of physical matter at a location. Although habitat structure is the physical template underlying ecological patterns and processes, the concept is relatively unappreciated and underdeveloped in ecology. However, it provides a fundamental concept for urban ecology because human activities in urban ecosystems are often targeted toward management of habitat structure. In addition, the concept emphasizes the fine-scale, on-the-ground perspective needed in the study of urban soil ecology. To illustrate this, urban soil ecology research is summarized from the perspective of habitat structure effects. Among the key conclusions emerging from the literature review are: (1) habitat structure provides a unifying theme for multivariate research about urban soil ecology; (2) heterogeneous urban habitat structures influence soil ecological variables in different ways; (3) more research is needed to understand relationships among sociological variables, habitat structure patterns and urban soil ecology. To stimulate urban soil ecology research, a conceptual framework is presented to show the direct and indirect relationships among habitat structure and ecological variables. Because habitat structure serves as a physical link between sociocultural and ecological systems, it can be used as a focus for interdisciplinary and applied research (e.g., pest management) about the multiple, interactive effects of urbanization on the ecology of soils

Dense matter with eXTP

In this White Paper we present the potential of the Enhanced X-ray Timing and Polarimetry (eXTP) mission for determining the nature of dense matter; neutron star cores host an extreme density regime which cannot be replicated in a terrestrial laboratory. The tightest statistical constraints on the dense matter equation of state will come from pulse profile modelling of accretion-powered pulsars, burst oscillation sources, and rotation-powered pulsars. Additional constraints will derive from spin measurements, burst spectra, and properties of the accretion flows in the vicinity of the neutron star. Under development by an international Consortium led by the Institute of High Energy Physics of the Chinese Academy of Science, the eXTP mission is expected to be launched in the mid 2020s.Comment: Accepted for publication on Sci. China Phys. Mech. Astron. (2019

Parameter estimation for strong phase transitions in supranuclear matter using gravitational-wave astronomy

At supranuclear densities, explored in the core of neutron stars, a strong phase transition from hadronic matter to more exotic forms of matter might be present. To test this hypothesis, binary neutron-star mergers offer a unique possibility to probe matter at densities that we can not create in any existing terrestrial experiment. In this work, we show that, if present, strong phase transitions can have a measurable imprint on the binary neutron-star coalescence and the emitted gravitational-wave signal. We construct a new parameterization of the supranuclear equation of state that allows us to test for the existence of a strong phase transition and extract its characteristic properties purely from the gravitational-wave signal of the inspiraling neutron stars. We test our approach using a Bayesian inference study simulating 600 signals with three different equations of state and find that for current gravitational-wave detector networks already twelve events might be sufficient to verify the presence of a strong phase transition. Finally, we use our methodology to analyze GW170817 and GW190425, but do not find any indication that a strong phase transition is present at densities probed during the inspiral.Comment: 17 pages, 11 figure

Back and Forth: Reverse Phase Transitions in Numerical Relativity Simulations

Multi-messenger observations of binary neutron star mergers provide a uniqueopportunity to constrain the dense-matter equation of state. Although it isknown from quantum chromodynamics that hadronic matter will undergo a phasetransition to exotic forms of matter, e.g., quark matter, the onset density ofsuch a phase transition cannot be computed from first principles. Hence, itremains an open question if such phase transitions occur inside isolatedneutron stars or during binary neutron star mergers, or if they appear at evenhigher densities that are not realized in the Cosmos. In this article, weperform numerical-relativity simulations of neutron-star mergers andinvestigate scenarios in which the onset density of such a phase transition isexceeded in at least one inspiralling binary component. Our simulations revealthat shortly before the merger it is possible that such stars undergo a"reverse phase transition", i.e., densities decrease and the quark core insidethe star disappears leaving a purely hadronic star at merger. After the merger,when densities increase once more, the phase transition occurs again and leads,in the cases considered in this work, to a rapid formation of a black hole. Wecompute the gravitational-wave signal and the mass ejection for our simulationsof such scenarios and find clear signatures that are related to the postmergerphase transition, e.g., smaller ejecta masses due to the softening of theequation of state through the quark core formation. Unfortunately, we do notfind measurable imprints of the reverse phase transition.<br

Neutrino Signatures From Young Neutron Stars

After a successful core collapse supernova (CCSN) explosion, a hot dense proto-neutron star (PNS) is left as a remnant. Over a time of 20 or so seconds, this PNS emits the majority of the neutrinos that come from the CCSN, contracts, and loses most of its lepton number. This is the process by which all neutron stars in our galaxy are likely born. The emitted neutrinos were detected from supernova (SN) 1987A, and they will be detected in much greater numbers from any future galactic CCSN. These detections can provide a direct window into the properties of the dense matter encountered inside neutron stars, and they can affect nucleosynthesis in the material ejected during the CCSN. In this chapter, we review the basic physics of PNS cooling, including the basic equations of PNS structure and neutrino diffusion in dense matter. We then discuss how the nuclear equation of state, neutrino opacities in dense matter, and convection can shape the temporal behavior of the neutrino signal. We also discuss what was learned from the late-time SN 1987A neutrinos, the prospects for detection of these neutrinos from future galactic CCSNe, and the effects these neutrinos can have on nucleosynthesis

Glucagon-Like Peptide-1 Protects Human Islets against Cytokine-Mediated β-Cell Dysfunction and Death: A Proteomic Study of the Pathways Involved

Glucagon-like peptide-1 (GLP-1) has been shown to protect pancreatic β-cells against cytokine-induced dysfunction and destruction. The mechanisms through which GLP-1 exerts its effects are complex and still poorly understood. The aim of this study was to analyze the protein expression profiles of human islets of Langerhans treated with cytokines (IL-1β and IFN-γ) in the presence or absence of GLP-1 by 2D difference gel electrophoresis and subsequent protein interaction network analysis to understand the molecular pathways involved in GLP-1-mediated β-cell protection. Co-incubation of cytokine-treated human islets with GLP-1 resulted in a marked protection of β-cells against cytokine-induced apoptosis and significantly attenuated cytokine-mediated inhibition of glucose-stimulated insulin secretion. The cytoprotective effects of GLP-1 coincided with substantial alterations in the protein expression profile of cytokine-treated human islets, illustrating a counteracting effect on proteins from different functional classes such as actin cytoskeleton, chaperones, metabolic proteins, and islet regenerating proteins. In summary, GLP-1 alters in an integrated manner protein networks in cytokine-exposed human islets while protecting them against cytokine-mediated cell death and dysfunction. These data illustrate the beneficial effects of GLP-1 on human islets under immune attack, leading to a better understanding of the underlying mechanisms involved, a prerequisite for improving therapies for diabetic patients.status: publishe

Nuclear Physics Multimessenger Astrophysics Constraints on the Neutron Star Equation of State: Adding NICER's PSR J0740+6620 Measurement

In the past few years, new observations of neutron stars (NSs) and NS mergers have provided a wealth of data that allow one to constrain the equation of state (EOS) of nuclear matter at densities above nuclear saturation density. However, most observations were based on NSs with masses of about 1.4 M⊙, probing densities up to ∼three to four times the nuclear saturation density. Even higher densities are probed inside massive NSs such as PSR J0740+6620. Very recently, new radio observations provided an update to the mass estimate for PSR J0740+6620, and X-ray observations by the NICER and XMM telescopes constrained its radius. Based on these new measurements, we revisit our previous nuclear physics multimessenger astrophysics constraints and derive updated constraints on the EOS describing the NS interior. By combining astrophysical observations of two radio pulsars, two NICER measurements, the two gravitational-wave detections GW170817 and GW190425, detailed modeling of the kilonova AT 2017gfo, and the gamma-ray burst GRB 170817A, we are able to estimate the radius of a typical 1.4 M⊙ NS to be 11.94-0.87+0.76 km at 90% confidence. Our analysis allows us to revisit the upper bound on the maximum mass of NSs and disfavors the presence of a strong first-order phase transition from nuclear matter to exotic forms of matter, such as quark matter, inside NSs