Hints towards the Emergent Nature of Gravity

A possible way out of the conundrum of quantum gravity is the proposal that general relativity (GR) is not a fundamental theory but emerges from an underlying microscopic description. Despite recent interest in the emergent gravity program within the physics as well as the philosophy community, an assessment of the theoretical evidence for this idea is lacking at the moment. We intend to fill this gap in the literature by discussing the main arguments in favour of the hypothesis that the metric field and its dynamics are emergent. First, we distinguish between microstructure inspired from GR, such as through quantization or discretization, and microstructure that is not directly motivated from GR, such as strings, quantum bits or condensed matter fields. The emergent gravity approach can then be defined as the view that the metric field and its dynamics are derivable from the latter type of microstructure. Subsequently, we assess in how far the following properties of (semi-classical) GR are suggestive of underlying microstructure: (1) the metric's universal coupling to matter fields, (2) perturbative non-renormalizability, (3) black hole thermodynamics, and (4) the holographic principle. In the conclusion we formalize the general structure of the plausibility arguments put forward.Comment: 36 pages, v2: minor additions, references added. Journal version in Studies in History and Philosophy of Modern Physic

Intra-islet GLP-1, but not CCK, is necessary for β-cell function in mouse and human islets

Glucagon-like peptide 1 (GLP-1) and cholecystokinin (CCK) are gut-derived peptide hormones known to play important roles in the regulation of gastrointestinal motility and secretion, appetite, and food intake. We have previously demonstrated that both GLP-1 and CCK are produced in the endocrine pancreas of obese mice. Interestingly, while GLP-1 is well known to stimulate insulin secretion by the pancreatic β-cells, direct evidence of CCK promoting insulin release in human islets remains to be determined. Here, we tested whether islet-derived GLP-1 or CCK is necessary for the full stimulation of insulin secretion. We confirm that mouse pancreatic islets secrete GLP-1 and CCK, but only GLP-1 acts locally within the islet to promote insulin release ex vivo. GLP-1 is exclusively produced in approximately 50% of α-cells in lean mouse islets and 70% of α-cells in human islets, suggesting a paracrine α to β-cell signaling through the β-cell GLP-1 receptor. Additionally, we provide evidence that islet CCK expression is regulated by glucose, but its receptor signaling is not required during glucose-stimulated insulin secretion (GSIS). We also see no increase in GSIS in response to CCK peptides. Importantly, all these findings were confirmed in islets from non-diabetic human donors. In summary, our data suggest no direct role for CCK in stimulating insulin secretion and highlight the critical role of intra-islet GLP-1 signaling in the regulation of human β-cell function

A Versatile, Portable Intravital Microscopy Platform for Studying Beta-cell Biology In Vivo

The pancreatic islet is a complex micro-organ containing numerous cell types, including endocrine, immune, and endothelial cells. The communication of these systems is lost upon isolation of the islets, and therefore the pathogenesis of diabetes can only be fully understood by studying this organized, multicellular environment in vivo. We have developed several adaptable tools to create a versatile platform to interrogate β-cell function in vivo. Specifically, we developed β-cell-selective virally-encoded fluorescent protein biosensors that can be rapidly and easily introduced into any mouse. We then coupled the use of these biosensors with intravital microscopy, a powerful tool that can be used to collect cellular and subcellular data from living tissues. Together, these approaches allowed the observation of in vivo β-cell-specific ROS dynamics using the Grx1-roGFP2 biosensor and calcium signaling using the GcAMP6s biosensor. Next, we utilized abdominal imaging windows (AIW) to extend our in vivo observations beyond single-point terminal measurements to collect longitudinal physiological and biosensor data through repeated imaging of the same mice over time. This platform represents a significant advancement in our ability to study β-cell structure and signaling in vivo, and its portability for use in virtually any mouse model will enable meaningful studies of β-cell physiology in the endogenous islet niche

The D0 Run IIb Luminosity Measurement

An assessment of the recorded integrated luminosity is presented for data collected with the D0 detector at the Fermilab Tevatron Collider from June 2006 to September 2011 (Run IIb). In addition, a measurement of the effective cross section for inelastic interactions, also referred to as the luminosity constant, is reported. This measurement incorporates new features that lead to a substantial improvement in the precision of the result. A luminosity constant of \sigma_{LM} = 48.3\pm1.9\pm0.6 mb is obtained, where the first uncertainty is due to the accuracy of the inelastic cross section used by both CDF and D0, and the second uncertainty is due to D0 sources. The recorded luminosity for the highest E_T jet trigger is L_rec = 9.2 \pm 0.4 fb^{-1}, with a relative uncertainty of 4.3%.Comment: 20 pages, 23 figure

Extraction methods and food uses of a natural red colorant from dye sorghum

BACKGROUND: The interest in stable natural colorants for food applications continues to grow. A red pigment extracted from the leaf sheaths of a sorghum variety (Sorghum bicolor) with a high content of apigeninidin is widely used as a biocolorant in processed foods in West Africa. This study compared the colour and anthocyanin composition from traditional extraction methods to determine options for improvement and use of the red biocolorant from dye sorghum in the food sector. RESULTS: Sorghum biocolorant was commonly applied in fermented and heated foods. Traditional extraction methods predominantly differed in two aspects, namely the use of an alkaline rock salt (locally known as kanwu) and the temperature of the extraction water. Cool extraction using the alkaline ingredient was more efficient than hot alkaline and hot aqueous extractions in extracting anthocyanins. The apigeninidin content was three times higher in the cool and hot alkaline extracts than in the aqueous extract. CONCLUSION: Cool and hot alkaline extractions at pH8-9 were the most efficient methods for extracting apigeninidin from dye sorghum leaf sheaths. Broader use of the sorghum biocolorant in foods requires further research on its effects on nutrient bioavailability and antioxidant activity

Pancreatic beta cell autophagy is impaired in type 1 diabetes

Aims/hypothesis Pancreatic beta cells are subjected to exogenous damaging factors such as proinflammatory cytokines or excess glucose that can cause accumulation of damage-inducing reactive oxygen species during the pathogenesis of diabetes. We and others have shown that beta cell autophagy can reduce reactive oxygen species to protect against apoptosis. While impaired islet autophagy has been demonstrated in human type 2 diabetes, it is unknown if islet autophagy is perturbed in the pathogenesis of type 1 diabetes. We hypothesised that beta cell autophagy is dysfunctional in type 1 diabetes, and that there is a progressive loss during early diabetes development. Methods Pancreases were collected from chloroquine-injected and non-injected non-obese diabetes-resistant (NOR) and non-obese diabetic (NOD) mice. Age- and BMI-matched pancreas tissue sections from human organ donors (N = 34) were obtained from the Network for Pancreatic Organ Donors with Diabetes (nPOD). Tissue sections were stained with antibodies against proinsulin or insulin (beta cell markers), microtubule-associated protein 1 light chain 3 A/B (LC3A/B; autophagosome marker), lysosomal-associated membrane protein 1 (LAMP1; lysosome marker) and p62 (autophagy adaptor). Images collected on a scanning laser confocal microscope were analysed with CellProfiler and ImageJ. Secondary lysosomes and telolysosomes were assessed in electron micrographs of human pancreatic tissue sections (n = 12), and energy dispersive x-ray analysis was performed to assess distribution of elements (n = 5). Results We observed increased autophagosome numbers in islets of diabetic NOD mice (p = 0.008) and increased p62 in islets of both non-diabetic and diabetic NOD mice (p < 0.001) vs NOR mice. There was also a reduction in LC3-LAMP1 colocalisation in islets of diabetic NOD mice compared with both non-diabetic NOD (p < 0.001) and NOR mice (p < 0.001). Chloroquine elicited accumulation of autophagosomes in the islets of NOR (p = 0.003) and non-diabetic NOD mice (p < 0.001), but not in islets of diabetic NOD mice; and stimulated accumulation of p62 in NOR (p < 0.001), but not in NOD mice. We observed reduced LC3-LAMP1 colocalisation (p < 0.001) in residual beta cells of human donors with type 1 diabetes vs non-diabetic participants. We also observed reduced colocalisation of proinsulin with LAMP1 in donors with type 1 diabetes (p < 0.001). Electron microscopy also revealed accumulation of telolysosomes with nitrogen-dense rings in beta cells of autoantibody-positive donors (p = 0.002). Conclusions/interpretation We provide evidence of islet macroautophagy/crinophagy impairment in human type 1 diabetes. We also document accumulation of telolysosomes with peripheral nitrogen in beta cells of autoantibody-positive donors, demonstrating altered lysosome content that may be associated with lysosome dysfunction before clinical hyperglycaemia. Similar macroautophagy impairments are present in the NOD mouse model of type 1 diabetes

Identification of mixed-symmetry states in an odd-mass nearly-spherical nucleus

The low-spin structure of 93Nb has been studied using the (n,n' gamma) reaction at neutron energies ranging from 1.5 to 3.0 MeV and the 94Zr(p,2n gamma)93Nb reaction at bombarding energies from 11.5 to 19 MeV. States at 1779.7 and 1840.6 keV, respectively, are proposed as mixed-symmetry states associated with the coupling of a proton hole in the p_1/2 orbit to the 2+_1,ms state in 94Mo. These assignments are derived from the observed M1 and E2 transition strengths to the symmetric one-phonon states, energy systematics, spins and parities, and comparison with shell model calculations.Comment: 5 pages, 3 figure

Lifetime determination of excited states in Cd-106

Two separate experiments using the Differential Decay Curve Method have been performed to extract mean lifetimes of excited states in 106 Cd. The inedium-spin states of interest were populated by the Mo-98(C-12, 4n) Cd-106 reaction performed at the Wright Nuclear Structure Lab., Yale University. From this experiment, two isomeric state mean lifetimes have been deduced. The low-lying states were populated by the Mo-96(C-13, 3n)Cd-106 reaction performed at the Institut fur Kernphysik, Universitat zu Koln. The mean lifetime of the I-pi = 2(1)(+) state was deduced, tentatively, as 16.4(9) ps. This value differs from the previously accepted literature value from Coulomb excitation of 10.43(9) ps

Currency Unions and Trade: A PPML Re-Assessment with High-Dimensional Fixed Effects

Recent work on the effects of currency unions (CUs) on trade stresses the importance of using many countries and years in order to obtain reliable estimates. However, for large samples, computational issues associated with the three-way (exporter-time, importer-time, and country-pair) fixed effects currently recommended in the gravity literature have heretofore limited the choice of estimator, leaving an important methodological gap. To address this gap, we introduce an iterative Poisson Pseudo-Maximum Likelihood (PPML) estimation procedure that facilitates the inclusion of these fixed effects for large data sets and also allows for correlated errors across countries and time. When applied to a comprehensive sample with more than 200 countries trading over 65 years, these innovations flip the conclusions of an otherwise rigorously-specified linear model. Most importantly, our estimates for both the overall CU effect and the Euro effect specifically are economically small and statistically insignificant. We also document that linear and PPML estimates of the Euro effect increasingly diverge as the sample size grows