The metabolic abnormalities of type 2 diabetes can be reversed reproducibly by bariatric surgery. By quantifying the major pathophysiological abnormalities in insulin secretion and insulin action ...after surgery, the sequence of events leading to restoration of normal metabolism can be defined. Liver fat levels fall within days and normal hepatic insulin sensitivity is restored. Simultaneously, plasma glucose levels return towards normal. Insulin sensitivity of muscle remains abnormal, at least over the weeks and months after bariatric surgery. The effect of the surgery is explicable solely in terms of energy restriction. By combining this information with prospective observation of the changes immediately preceding the onset of type 2 diabetes, a clear picture emerges. Insulin resistance in muscle, caused by inherited and environmental factors, facilitates the development of fatty liver during positive energy balance. Once established, the increased insulin secretion required to maintain plasma glucose levels will further increase liver fat deposition. Fatty liver causes resistance to insulin suppression of hepatic glucose output as well as raised plasma triacylglycerol. Exposure of beta cells to increased levels of fatty acids, derived from circulating and locally deposited triacylglycerol, suppresses glucose-mediated insulin secretion. This is reversible initially, but eventually becomes permanent. The essential time sequence of the pathogenesis of type 2 diabetes is now evident. Muscle insulin resistance determines the rate at which fatty liver progresses, and ectopic fat deposition in liver and islet underlies the related dynamic defects of hepatic insulin resistance and beta cell dysfunction. These defects are capable of dramatic reversal under hypoenergetic feeding conditions, completely in early diabetes and to a worthwhile extent in more established disease.
This paper summarizes a strategy for supplying ecosystem services in urban areas through a participatory planning process targeting multifunctional green infrastructure. We draw from the literature ...on landscape multifunctionality, which has primarily been applied to agricultural settings, and propose opportunities to develop urban green infrastructure that could contribute to the sustainable social and ecological health of the city. Thinking in terms of system resilience, strategies might focus on the potential for green infrastructure to allow for adaptation and even transformation in the face of future challenges such as climate change, food insecurity, and limited resources. Because planning for multiple functions can be difficult when many diverse stakeholders are involved, we explored decision support tools that could be applied to green infrastructure planning in the early stages, to engage the public and encourage action toward implementing a preferred solution. Several specific ecosystem services that could be relevant for evaluating current and future urban green spaces include: plant biodiversity, food production, microclimate control, soil infiltration, carbon sequestration, visual quality, recreation, and social capital. Integrating such ecosystem services into small-scale greening projects could allow for creativity and local empowerment that would inspire broader transformation of green infrastructure at the city level. Those cities committing to such an approach by supporting greening projects are likely to benefit in the long run through the value of ecosystem services for urban residents and the broader public.
It has become widely accepted that Type 2 diabetes is inevitably life‐long, with irreversible and progressive beta cell damage. However, the restoration of normal glucose metabolism within days after ...bariatric surgery in the majority of people with Type 2 diabetes disproves this concept. There is now no doubt that this reversal of diabetes depends upon the sudden and profound decrease in food intake, and does not relate to any direct surgical effect. The Counterpoint study demonstrated that normal glucose levels and normal beta cell function could be restored by a very low calorie diet alone. Novel magnetic resonance methods were applied to measure intra‐organ fat. The results showed two different time courses: a) resolution of hepatic insulin sensitivity within days along with a rapid fall in liver fat and normalisation of fasting glucose levels; and b) return of normal beta cell insulin secretion over weeks in step with a fall in pancreas fat. Now that it has been possible to observe the pathophysiological events during reversal of Type 2 diabetes, the reverse time course of events which determine the onset of the condition can be identified. The twin cycle hypothesis postulates that chronic calorie excess leads to accumulation of liver fat with eventual spill over into the pancreas. These self‐reinforcing cycles between liver and pancreas eventually cause metabolic inhibition of insulin secretion after meals and onset of hyperglycaemia. It is now clear that Type 2 diabetes is a reversible condition of intra‐organ fat excess to which some people are more susceptible than others.
A
bstract
We study tree-level celestial amplitudes in Yang-Mills theory — Mellin transforms of multi-gluon scattering amplitudes that convert them into the correlators of conformal primary fields on ...two-dimensional celestial sphere. By using purely field-theoretical methods, we show that the soft conformal limit of celestial amplitudes, in which one of the primary field operators associated to gauge bosons becomes a dimension one current, is dominated by the contributions of low-energy soft particles. This result confirms conclusions reached by using Yang-Mills theory formulated in curvilinear coordinates, as pioneered by Strominger. By using well-known collinear limits of Yang-Mills amplitudes, we derive the OPE rules for the primary fields and the holomorphic currents arising in the conformally soft limit. The Ward identities following from OPE have the same form as the identities derived by using soft theorems.
Primary fields in celestial CFT Fotopoulos, Angelos; Taylor, Tomasz R.
The journal of high energy physics,
10/2019, Letnik:
2019, Številka:
10
Journal Article
Recenzirano
Odprti dostop
A
bstract
The basic ingredient of CCFT holography is to regard four-dimensional amplitudes describing conformal wave packets as two-dimensional conformal correlation functions of the operators ...associated to external particles. By construction, these operators transform as quasi-primary fields under SL(2, ℂ) conformal symmetry group of the celestial sphere. We derive the OPE of the CCFT energy-momentum tensor with the operators representing gauge bosons and show that they transform as Virasoro primaries under diffeomorphisms of the celestial sphere.
The first and higher harmonic components of the resonant fluid response in the gap between two identical fixed rectangular boxes are experimentally investigated in a wave basin. Gap response is ...excited by transient wave groups (being based on scaled versions of the autocorrelation function of sea-state spectra, representing NewWaves, the average shape of large waves in a sea state). Several different wave groups with different maximum surface elevations, spectral peak frequencies and bandwidths are used, while the bilge shape of the boxes and approach angle of the waves are also varied. Unlike a simple regular wave, it is complicated to separate the harmonic components for a transient wave group due to nonlinear wave–wave and wave–structure interactions. A four-phase combination methodology is used to separate the first four harmonic components, and this also allows higher harmonic components to be isolated with simple digital frequency filtering. Harmonic components up to 14th order in the incident wave amplitude have been extracted. It is shown that for an incident group with appropriate frequency content, the linear gap response may be substantially smaller than the second harmonic component, which is strongly driven via quadratic coupling of the linear terms from the incident wave and occurs in the gap resonant modes. Double frequency excitation may have important practical implications for offshore operations. Fourth and zeroth (long-wave) harmonics in the gap are further driven via quadratic coupling of the second harmonic itself. Linear damping coefficients for the first few modes of the gap resonant response are derived from measured time series using a numerical fit and shown to be higher than those from linear diffraction calculations.
Liver cirrhosis is a major cause of death worldwide and is characterized by extensive fibrosis. There are currently no effective antifibrotic therapies available. To obtain a better understanding of ...the cellular and molecular mechanisms involved in disease pathogenesis and enable the discovery of therapeutic targets, here we profile the transcriptomes of more than 100,000 single human cells, yielding molecular definitions for non-parenchymal cell types that are found in healthy and cirrhotic human liver. We identify a scar-associated TREM2
CD9
subpopulation of macrophages, which expands in liver fibrosis, differentiates from circulating monocytes and is pro-fibrogenic. We also define ACKR1
and PLVAP
endothelial cells that expand in cirrhosis, are topographically restricted to the fibrotic niche and enhance the transmigration of leucocytes. Multi-lineage modelling of ligand and receptor interactions between the scar-associated macrophages, endothelial cells and PDGFRα
collagen-producing mesenchymal cells reveals intra-scar activity of several pro-fibrogenic pathways including TNFRSF12A, PDGFR and NOTCH signalling. Our work dissects unanticipated aspects of the cellular and molecular basis of human organ fibrosis at a single-cell level, and provides a conceptual framework for the discovery of rational therapeutic targets in liver cirrhosis.
•Extant research on minimalism views consumers as homogeneous and not heterogeneous.•The antecedents and motives of minimalistic consumption are identified.•The research gap is addressed through ...developing a consumer typology.•Firms can design strategies to satisfy the unique goals for each consumer segment.
Minimalistic consumption has received increased attention during the last few years with a substantial segment of consumers having adopted this notion. Minimalism highlights subjective well-being, happiness, and increased quality of life. Despite minimalism gaining significance, we know little about minimalistic consumption, its various forms, its antecedents, and its impact on consumer behavior. Extant literature does not offer a clear or concise conceptualization of minimalism in consumption or the potential strategies to identify, target, and engage minimalistic consumers. This has been a major deterrent in advancing research on minimalistic consumption. This article provides a conceptualization of minimalism and offers a typology of consumers that engage in minimalistic consumption based on two dimensions: the conditional susceptibility and goal orientation of consumers. It presents a framework of brand engagement strategies for each type of consumer and shows how firms can potentially benefit in terms of sales, profitability, and customer relationships by engaging with minimalistic consumers.
There are ~463 million diabetics worldwide, and more than half have diabetic retinopathy. Yet, treatments are still lacking for non-proliferative diabetic retinopathy. We and others previously ...provided evidence that Interleukin-17A (IL-17A) plays a pivotal role in non-proliferative diabetic retinopathy. However, all murine studies used Type I diabetes models. Hence, it was the aim of this study to determine if IL-17A induces non-proliferative diabetic retinopathy in Type II diabetic mice, as identified for Type I diabetes. While examining the efficacy of anti-IL-17A as a potential therapeutic in a short-term Type I and a long-term Type II diabetes model; using different routes of administration of anti-IL-17A treatments. Retinal inflammation was significantly decreased (p < 0.05) after Type I-diabetic mice received 1 intravitreal injection, and Type II-diabetic mice received seven intraperitoneal injections of anti-IL-17A. Further, vascular tight junction protein Zonula Occludens-1 (ZO-1) was significantly decreased in both Type I and II diabetic mice, which was significantly increased when mice received anti-IL-17A injections (p < 0.05). Similarly, tight junction protein Occludin degradation was halted in Type II diabetic mice that received anti-IL-17A treatments. Finally, retinal capillary degeneration was halted 6 months after diabetes was confirmed in Type II-diabetic mice that received weekly intraperitoneal injections of anti-IL-17A. These findings provide evidence that IL-17A plays a pivotal role in non-proliferative diabetic retinopathy in Type II diabetic mice, and suggests that anti-IL-17A could be a good therapeutic candidate for non-proliferative diabetic retinopathy.
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