Loop Model Research Articles

Pathogenic diversification of the gut commensal Providencia alcalifaciens via acquisition of a second type III secretion system.

Providencia alcalifaciens is a Gram-negative bacterium found in a wide variety of water and land environments and organisms. It has been isolated as part of the gut microbiome of animals and insects, as well as from stool samples of patients with diarrhea. Specific P. alcalifaciens strains encode gene homologs of virulence factors found in other pathogenic members of the same Enterobacterales order, such as Salmonella enterica serovar Typhimurium and Shigella flexneri. Whether these genes are also pathogenic determinants in P. alcalifaciens is not known. Here we have used P. alcalifaciens 205/92, a clinical isolate, with in vitro and in vivo infection models to investigate P. alcalifaciens -host interactions at the cellular level. Our particular focus was the role of two type III secretion systems (T3SS) belonging to the Inv-Mxi/Spa family. T3SS 1b is widespread in Providencia spp. and encoded on the chromosome. T3SS 1a is encoded on a large plasmid that is present in a subset of P. alcalifaciens strains, which are primarily isolates from diarrheal patients. Using a combination of electron and fluorescence microscopy and gentamicin protection assays we show that P. alcalifaciens 205/92 is internalized into eukaryotic cells, rapidly lyses its internalization vacuole and proliferates in the cytosol. This triggers caspase-4 dependent inflammasome responses in gut epithelial cells. The requirement for the T3SS 1a in entry, vacuole lysis and cytosolic proliferation is host-cell type specific, playing a more prominent role in human intestinal epithelial cells as compared to macrophages. In a bovine ligated intestinal loop model, P. alcalifaciens colonizes the intestinal mucosa, inducing mild epithelial damage with negligible fluid accumulation. No overt role for T3SS 1a or T3SS 1b was seen in the calf infection model. However, T3SS 1b was required for the rapid killing of Drosophila melanogaster . We propose that the acquisition of two T3SS by horizontal gene transfer has allowed P. alcalifaciens to diversify its host range, from a highly virulent pathogen of insects to an opportunistic gastrointestinal pathogen of animals.

A Products Liability Framework for AI

A products liability framework, drawing inspiration from the regulation of FDA-approved medical products—which includes federal regulation as well as products liability—holds great promise for tackling many of the challenges AI poses. Notwithstanding the new challenges that sophisticated AI technologies pose, products liability provides a conceptual framework capable of responding to the learning and iterative aspects of these technologies. Moreover, this framework provides a robust model of the feedback loop between tort liability and regulation.The regulation of medical products provides an instructive point of departure. The FDA has recognized the need to revise its traditional paradigm for medical device regulation to fit adaptive AI/ML technologies, which enable continuous improvements and modifications to devices based on information gathered during use. AI/ML technologies should hasten an even more significant regulatory paradigm shift at the FDA away from a model that puts most of its emphasis on (and resources into) ex ante premarket approval to one that highlights ongoing postmarket surveillance. As such a model takes form, products liability should continue to play a significant information-production and deterrence role, especially during the transition period before a new ex post regulatory framework is established.

Fast synchronization with enhanced switching control for grid-tied single-phase square wave inverter using FPGA

Research on grid synchronization has been conducted worldwide by researchers in conjunction with the development of innovative technologies, such as dedicated short-range communication (DSRC) and cellular vehicle-to-everything (C-V2X). However, grid-connected inverters face several challenges, mainly the mismatch in voltage amplitude, frequency, and phase angle, as well as grid voltage disturbance and grid faults. Thus, the control algorithm of this research mainly focused on a half-cycle algorithm to design an enhanced digital switching control for fast synchronization using an FPGA. The control algorithm was developed based on zero-crossing detection (ZCD) and digital phase-locked loop (PLL) modeling techniques using the hardware description language (HDL) and a combination of digital logic blocks in Quartus II software, where the proposed switching was applied using the square-wave switching technique through a 300-watt full-bridge experimental prototype. The performance of the proposed technique was studied, where the total harmonic distortion (THD) for voltage and current resulted in a percentage reduction of 89.29% and 78.05% for voltage and current, respectively, after filter implementation. Also, the resulting signal synchronized in every half cycle and matched the voltage amplitude, frequency, and phase angle of the grid signal in 10 ms.

Dynamic processes of positive/negative immune-vascular crosstalk loop via functional MRI-guided monitor

Immunotherapy holds significant promise to completely eliminate tumor, yet lack of timely evaluation of immune responses, which challenged by inherent lagging and pseudoprogression during immunotherapy. Immune-vascular crosstalk (IVC), an enhancement ring for the mutual regulation linking tumor vascular normalization with immune remodeling forms, emerging as a systematic indicator for immunotherapy outcomes, necessitates timely, non-invasive, and early detection of its status to enhance clinical benefits. Herein, positive and negative loop models of tumor IVC were established using different degree of photothermal therapy (PTT) based on NaBiF4:Gd@PDA@PEG nanoprobes. Multi-functional magnetic resonance imaging, including fast spoiled gradient-recalled (FSPGR), time-resolved imaging of contrast kinetics (TRICKs) and dynamic susceptibility contrast perfusion weighted imaging (DSC-PWI), was applied to dynamically reflect normalized/ablated tumor vasculature, well-matched increased/decreased immune response corresponding to different status of IVC, confirmed by pathology results. This study proposes a novel biological method to noninvasively detect the positive/negative IVC loop, paving the visualized way for immunotherapy assessed benefits, which is expected to be extended to clinical translation.

Highly Accurate and Efficient Deep Learning Paradigm for Full-Atom Protein Loop Modeling with KarmaLoop.

Protein loop modeling is a challenging yet highly nontrivial task in protein structure prediction. Despite recent progress, existing methods including knowledge-based, abinitio, hybrid, and deep learning (DL) methods fall substantially short of either atomic accuracy or computational efficiency. To overcome these limitations, we present KarmaLoop, a novel paradigm that distinguishes itself as the first DL method centered on full-atom (encompassing both backbone and side-chain heavy atoms) protein loop modeling. Our results demonstrate that KarmaLoop considerably outperforms conventional and DL-based methods of loop modeling in terms of both accuracy and efficiency, with the average RMSDs of 1.77 and 1.95 Å for the CASP13+14 and CASP15 benchmark datasets, respectively, and manifests at least 2 orders of magnitude speedup in general compared with other methods. Consequently, our comprehensive evaluations indicate that KarmaLoop provides a state-of-the-art DL solution for protein loop modeling, with the potential to hasten the advancement of protein engineering, antibody-antigen recognition, and drug design.

An alternate representation of the geomagnetic core field obtained using machine learning

Machine learning (ML) as a tool is rapidly emerging in various branches of contemporary geophysical research. To date, however, rarely has it been applied specifically for the study of Earth’s internal magnetic field and the geodynamo. Prevailing methods currently used in inferring the characteristic properties and the probable time evolution of the geodynamo are mostly based on reduced representations of magnetohydrodynamics (MHD). This study introduces a new inference method, referred to as Current Loop-based UNet Model Segmentation Inference (CLUMSI). Its long-term goal focuses on uncovering concentrations of electric current densities inside the core as the direct sources of the magnetic field itself, rather than computing the fluid motion using MHD. CLUMSI relies on simplified models in which equivalent current loops represent electric current systems emerging in turbulent geodynamo simulations. Various configurations of such loop models are utilized to produce synthetic magnetic field and secular variation (SV) maps computed at the core–mantle boundary (CMB). The resulting maps are then presented as training samples to an image-processing neural network designed specifically for solving image segmentation problems. This network essentially learns to infer the parameters and configuration of the loops in each model based on the corresponding CMB maps. In addition, with the help of the Domain Adversarial Training of Neural Networks (DANN) method during training, historical geomagnetic field data could also be considered alongside the synthetic samples. This implementation can increase the likelihood that a network trained primarily on synthetic data will appropriately handle real inputs. Our results focus mainly on the method's feasibility when applied to synthetic data and the quality of these inferences. A single evaluation of the trained network can recover the overall distribution of loop parameters with reasonable accuracy. To better represent conditions in the outer core, the study also proposes a computationally feasible process to account for magnetic diffusion and the corresponding induced currents in the loop models. However, the quality of the reconstruction of magnetic field properties is compromised by occasional poor inferences, and an inability to recover realistic SV.Graphical

Paediatric oncologists' perspectives on Strategic solutions to develop Integrated Cancer Palliative Care: feedback intervention theory as an explanatory Framework.

Globally, children with cancer often experience delays in palliative care referral or are infrequently referred. Therefore, we conducted a qualitative study to gain insight from paediatric oncologists into what enables or deters palliative care referral. Strategic solutions to develop integrated palliative care was a critical study theme. In this paper, we have explained and interpreted these strategic solutions through the lens of feedback intervention theory. The study findings were interpreted using Kumar's six-step approach that enabled systematic evaluation of a theory's appropriateness and alignment with the researcher's paradigm, methodology, and study findings. It also explained how theory informed analysis and elucidated challenges or the development of new models. The feedback intervention theory appraises the discrepancy between actual and desired goals and provides feedback to improve it. Strategic solutions generated from the study findings were coherent with the aspects elucidated in theory, like coping mechanisms, levels of feedback hierarchy, and factors determining the effect of the feedback intervention on performance. Paediatric oncologists suggested integrating palliative care providers in the team innocuously, improving communication between teams, relabelling palliative care as symptom control, and working with a skilled and accessible palliative care team. The paper proposes an infinite loop model developed from the study, which has the potential to foster integrated palliative care through excellent collaboration and continuous feedback. Applying feedback intervention theory can bridge the gap between actual and desired practice for integrated cancer palliative care in paediatric oncology.

Cascading supply chain disruption: impact on water industry during COVID-19

The impact of COVID-19 on the lives of people and businesses across the globe was devastating. While governments across the world had undertaken a slew of measures to control the spread of the COVID-19 virus within their geography, many of these measures had long and unintended consequences. The restrictions imposed by the governments on the movement of people and goods across the world brought supply chains to a grinding halt. This study identifies the cascading effects of supply chain disruptions on the water sector. Since these systems are closely integrated and the impact of COVID-19 needs to be analysed at a much broader level, this study uses a systems-thinking approach to study the effect of supply chain disruptions on water services. The study develops a causal loop model to gain further insight into how supply chain disruptions caused by COVID-19 affected the coping capabilities of society and how critical services were affected.

Next-Generation Dual Transceiver FSO Communication System for High-Speed Trains in Neom Smart City

Smart cities like Neom require efficient and reliable transportation systems to support their vision of sustainable and interconnected urban environments. High-speed trains (HSTs) play a crucial role in connecting different areas of the city and facilitating seamless mobility. However, to ensure uninterrupted communication along the rail lines, advanced communication systems are essential to expand the coverage range of each base station (BS) while reducing the handover frequency. This paper presents the dual transceiver free space optical (FSO) communication system as a solution to achieve these objectives in the operational environment of HSTs in Neom city. Our channel model incorporates log-normal (LN) and gamma–gamma (GG) distributions to represent channel impairments and atmospheric turbulence in the city. Furthermore, we integrated the siding loop model, providing valuable insights into the system in real-world scenarios. To assess the system’s performance, we formulated the received signal-to-noise ratio (SNR) of the network under assumed fading conditions. Additionally, we analyzed the system’s bit error rate (BER) analytically and through Monte Carlo simulation. A comparative analysis with reconfigurable intelligent surfaces (RIS) and relay-assisted FSO communications shows the superior coverage area and efficiency of the dual transceiver model. A significant reduction of up to 76% and 99% in the number of required BSs compared to RIS and relay, respectively, is observed. This reduction leads to fewer handovers and lower capital expenditure (CAPEX) costs.

SIMULATION OF TRANSIENT PROCESS ON WWER-1000 USING COUPLED APPROACH

Research and modeling of thermohydraulic processes in NPP equipment is necessary for a deep and improved justification of reliable and safe operation of nuclear installations. Taking into account the accumulated experience and the latest technologies, the study of thermohydraulic processes is developing in the direction of applying innovative approaches to conducting both experimental studies and expanding the calculation capabilities of thermohydraulic codes. The article presents an approach to the decomposition of the thermohydraulic model of the WWER-1000 reactor plant on submodels, which are calculated in coupling with separate instances of the system thermohydraulic code RELAP5/Mod 3.2. Coupling is implemented using a specially developed module. This approach allows you to "bypass" the internal limitations of RELAP5 in the number of components (hydrodynamic volumes, thermal structures, "trips" and control variables) that can be used for computational analysis. As a result, it becomes possible to achieve a higher degree of detail for the entire reactor installation. In addition, the article confirms the possibility of applying the previously developed coupling module to such a non-equilibrium model as a nuclear reactor model. At the same time, the use of the RELAP5 model as a reactor model makes it possible to avoid inaccuracies that arise when applying assumptions about the transverse profiles of the input variables of the CFX model, as well as to perform the validation of the RELAP5 model of the RU loops. Coupled calculation of stationary and transient mode of reactor installation WWER-1000 is performed. The reliability of calculation results obtained in conjugation is evaluated by comparing them with the results of autonomous calculations in RELAP5. The analysis of the results of computational modeling confirms the possibility of applying the developed coupling module to such a non-equilibrium model as a model of a nuclear reactor, and also confirms the correctness of the RELAP5 model of the loops of the reactor plant obtained on the basis of the modification of the full-fledged RELAP5 model.

Polyakov loop models in the large N limit: Correlation function and screening masses

We explore the ’t Hooft-Veneziano limit of the Polyakov loop models at finite baryon chemical potential. Using methods developed by us earlier we calculate the two- and N-point correlation functions of the Polyakov loops. This gives a possibility to compute the various potentials in the confinement phase and to derive the screening masses outside the confinement region. In particular, we establish the existence of complex masses and an oscillating decay of correlations in a certain range of parameters. Furthermore, it is shown that the calculation of the N-point correlation function in the confinement phase reduces to the geometric median problem. This leads to a large N analog of the Y law for the baryon potential. Published by the American Physical Society 2024

Resonant absorption of standing MHD waves in coronal loops in the absence of directional symmetry: the effect of weak plasma flow

ABSTRACT The oscillation properties of standing magnetohydrodynamic waves in coronal loops has been investigated. A coronal loop is modelled as a straight cylinder with purely axial magnetic field and field aligned plasma flow. The loop model includes an inhomogeneous transitional layer that causes the wave to be resonantly damped. Our aim is to obtain the solution describing a resonantly damped standing kink wave in a flowing loop with the directional symmetry of the loop being broken due to the presence of plasma flow. In the absence of damping the standing wave is a superposition of two waves propagating in the opposite directions that have the same frequency but different wavenumbers. However, the same approach cannot be used when there is damping because the decrements of the two propagating waves are different. We suggest that in the case of relatively weak flow, as is the case in coronal loops, the effect of flow on the decrements can be neglected. Then the decrements of the two waves are the same and the solution describing the damped standing kink wave is a superposition of two resonantly damped propagating waves.

In Vivo Engineering and Transplantation of Axially Vascularized and Epithelialized Flaps in Rats.

The arteriovenous loop (AVL) model allows the in vivo engineering of axially vascularized flaps, the so-called AVL flaps. Although AVL flaps can be transplanted microsurgically to cover tissue defects, they lack an epithelial layer on the surface. Therefore, the objective of this study was to engineer axially vascularized AVL flaps with an accompanying epithelial layer for local defect reconstruction. In this study, AVLs were established in 20 male Lewis rats. Minimally invasive injection of keratinocytes onto the surface of the AVL flaps was performed on postoperative day (POD) 21. AVL flaps were explanted from 12 rats on POD 24 or POD 30, then the epithelium formed by the keratinocytes on the surface of the flaps was evaluated using immunofluorescence staining. In six other rats, the AVL flap was locally transposed to cover a critical defect in the rats' leg on POD 30 and explanted for analysis on POD 40. In two control rats, sodium chloride was applied instead of keratinocytes. These control flaps were also transplanted on POD 30 and explanted on POD 40. Our results revealed that 3 days after keratinocyte application, a loose single-layered epithelium was observed histologically on the AVL flaps surface, whereas after 9 days, a multilayered and structured epithelium had grown. The epithelium on the transplanted AVL flaps showed its physiological differentiation when being exposed to an air-liquid interface. Histologically, a layered epithelium identical to the rats' regular skin was formed. In the sodium chloride control group, no epithelium had been grown. This study clearly demonstrates that axially vascularized AVL flaps can be processed in the subcutaneous chamber by minimally invasive injection of keratinocytes. Thus, AVL flaps with an intact epithelial layer were engineered and could be successfully transplanted for local defect coverage in a small animal model.

Glucose hypometabolism prompts RAN translation and exacerbates C9orf72-related ALS/FTD phenotypes.

The most prevalent genetic cause of both amyotrophic lateral sclerosis and frontotemporal dementia is a (GGGGCC)n nucleotide repeat expansion (NRE) occurring in the first intron of the C9orf72 gene (C9). Brain glucose hypometabolism is consistently observed in C9-NRE carriers, even at pre-symptomatic stages, but its role in disease pathogenesis is unknown. Here, we show alterations in glucose metabolic pathways and ATP levels in the brains of asymptomatic C9-BAC mice. We find that, through activation of the GCN2 kinase, glucose hypometabolism drives the production of dipeptide repeat proteins (DPRs), impairs the survival of C9 patient-derived neurons, and triggers motor dysfunction in C9-BAC mice. We also show that one of the arginine-rich DPRs (PR) could directly contribute to glucose metabolism and metabolic stress by inhibiting glucose uptake in neurons. Our findings provide a potential mechanistic link between energy imbalances and C9-ALS/FTD pathogenesis and suggest a feedforward loop model with potential opportunities for therapeutic intervention.

MUSE observations of small-scale heating events

ABSTRACT Constraining the processes that drive coronal heating from observations is a difficult task due to the complexity of the solar atmosphere. As upcoming missions such as the Multi-slit Solar Explorer (MUSE) will provide coronal observations with unprecedented spatial and temporal resolution, numerical simulations are becoming increasingly realistic. Despite the availability of synthetic observations from numerical models, line-of-sight effects and the complexity of the magnetic topology in a realistic set-up still complicate the prediction of signatures for specific heating processes. 3D magnetohydrodynamic (MHD) simulations have shown that a significant part of the Poynting flux injected into the solar atmosphere is carried by small-scale motions, such as vortices driven by rotational flows inside intergranular lanes. MHD waves excited by these vortices have been suggested to play an important role in the energy transfer between different atmospheric layers. Using synthetic spectroscopic data generated from a coronal loop model incorporating realistic driving by magnetoconvection, we study whether signatures of energy transport by vortices and eventual dissipation can be identified with future missions such as MUSE.

Spatial organisation of fungi in soil biocrusts of the Kalahari is related to bacterial community structure and may indicate ecological functions of fungi in drylands.

Biological soil crusts, or biocrusts, are microbial communities found in soil surfaces in drylands and in other locations where vascular plant cover is incomplete. They are functionally significant for numerous ecosystem services, most notably in the C fixation and storage due to the ubiquity of photosynthetic microbes. Whereas carbon fixation and storage have been well studied in biocrusts, the composition, function and characteristics of other organisms in the biocrust such as heterotrophic bacteria and especially fungi are considerably less studied and this limits our ability to gain a holistic understanding of biocrust ecology and function. In this research we characterised the fungal community in biocrusts developed on Kalahari Sand soils from a site in southwest Botswana, and combined these data with previously published bacterial community data from the same site. By identifying organisational patterns in the community structure of fungi and bacteria, we found fungi that were either significantly associated with biocrust or the soil beneath biocrusts, leading to the conclusion that they likely perform functions related to the spatial organisation observed. Furthermore, we showed that within biocrusts bacterial and fungal community structures are correlated with each other i.e., a change in the bacterial community is reflected by a corresponding change in the fungal community. Importantly, this correlation but that this correlation does not occur in nearby soils. We propose that different fungi engage in short-range and long-range interactions with dryland soil surface bacteria. We have identified fungi which are candidates for further studies into their potential roles in biocrust ecology at short ranges (e.g., processing of complex compounds for waste management and resource provisioning) and longer ranges (e.g., translocation of resources such as water and the fungal loop model). This research shows that fungi are likely to have a greater contribution to biocrust function and dryland ecology than has generally been recognised.

On currents in the $O(n)$ loop model

Using methods from the conformal bootstrap, we study the properties of Noether currents in the critical O(n)O(n) loop model. We confirm that they do not give rise to a Kac-Moody algebra (for n≠ 2n≠2), a result expected from the underlying lack of unitarity. By studying four-point functions in detail, we fully determine the current-current OPEs, and thus obtain several structure constants with physical meaning. We find in particular that the terms :\!J\bar{J}\!::JJ‾: in the identity and adjoint channels vanish exactly, invalidating the argument made in [Nucl. Phys. B 419, 411 (1994)] that adding orientation-dependent interactions to the model should lead to continuously varying exponents in self-avoiding walks. We also determine the residue of the identity channel in the JJJJ two-point function, finding that it coincides both with the result of a transfer-matrix computation for an orientation-dependent correlation function in the lattice model, and with an earlier Coulomb gas computation of Cardy [Nucl. Phys. B 265, 409 (1986)]. This is, to our knowledge, one of the first instances where the Coulomb gas formalism and the bootstrap can be successfully compared.

Prediction of tensile behavior of compression therapeutic biomedical materials by mesoscale laid-in loop model

Tubular laid-in weft-knitted compression (LWC) therapeutic materials have been extensively applied in medical clinic treatment and daily healthcare management. Limited studies have explored the mechanical mechanisms through the numerical analytical models for the development and performance prediction of laid-in fabrics. This study developed the three-dimensional (3D) finite element (FE) laid-in loop model to simulate and predict the tensile behaviors of LWC materials based on the determination of geometric models and investigation of yarn mechanical properties. Through the constructed FE mesoscale models with various physical-mechanical characteristics of inlay yarn materials, it was found that the ground yarns and inlay yarns played distinct roles in producing tensile stresses under the course and wale direction of stretching strains. These tensile stresses determined the selection of yarn materials for controlling the tension of laid-in knitted fabrics in end applications. Then, the interfacial pressure dosages exerted by LWC materials were quantitively obtained based on the simulated Young's moduli values and modification of Laplace's Law model. The accuracy and acceptability of proposed mechanical laid-in models (mean error: 10.22 %) and pressure prediction models (mean error: 14.70 %) were validated by the comparative studies. The simulation methods and results created a visual tool for dynamically illustrating the tensile behaviors and predicting pressure performances of the elastic therapeutic materials in functional material design of biomedical compression textiles.

Integrability of rank-two web models

We continue our work on lattice models of webs, which generalise the well-known loop models to allow for various kinds of bifurcations [1,2]. Here we define new web models corresponding to each of the rank-two spiders considered by Kuperberg [3]. These models are based on the A2, G2 and B2 Lie algebras, and their local vertex configurations are intertwiners of the corresponding q-deformed quantum algebras. In all three cases we define a corresponding model on the hexagonal lattice, and in the case of B2 also on the square lattice. For specific root-of-unity choices of q, we show the equivalence to a number of three- and four-state spin models on the dual lattice.The main result of this paper is to exhibit integrable manifolds in the parameter spaces of each web model. For q on the unit circle, these models are critical and we characterise the corresponding conformal field theories via numerical diagonalisation of the transfer matrix.In the A2 case we find two integrable regimes. The first one contains a dense and a dilute phase, for which we have analytic control via a Coulomb gas construction, while the second one is more elusive and likely conceals non-compact physics. Three particular points correspond to a three-state spin model with plaquette interactions, of which the one in the second regime appears to present a new universality class. In the G2 case we identify four regimes numerically. The B2 case is too unwieldy to be studied numerically in the general case, but it found analytically to contain a simpler sub-model based on generators of the dilute Birman-Murakami-Wenzl algebra.

Mathematical Models of the Effect of Glucagon on Glycemia in Individuals With Type 2 Diabetes Treated With Dapagliflozin.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors lower blood glucose levels by promoting urinary glucose excretion, but their overall effects on hormonal and metabolic status remain unclear. We here investigated the roles of insulin and glucagon in the regulation of glycemia in individuals treated with an SGLT2 inhibitor using mathematical model analysis. Hyperinsulinemic-euglycemic clamp and oral glucose tolerance tests were performed in 68 individuals with type 2 diabetes treated with the SGLT2 inhibitor dapagliflozin. Data previously obtained from such tests in 120 subjects with various levels of glucose tolerance and not treated with an SGLT2 inhibitor were examined as a control. Mathematical models of the feedback loops connecting glucose and insulin (GI model) or glucose, insulin, and glucagon (GIG model) were generated. Analysis with the GI model revealed that the disposition index/clearance, which is defined as the product of insulin sensitivity and insulin secretion divided by the square of insulin clearance and represents the glucose-handling ability of insulin, was significantly correlated with glycemia in subjects not taking an SGLT2 inhibitor but not in those taking dapagliflozin. Analysis with the GIG model revealed that a metric defined as the product of glucagon sensitivity and glucagon secretion divided by glucagon clearance (designated production index/clearance) was significantly correlated with blood glucose level in subjects treated with dapagliflozin. Treatment with an SGLT2 inhibitor alters the relation between insulin effect and blood glucose concentration, and glucagon effect may account for variation in glycemia among individuals treated with such drugs.