Synthetic Response Research Articles

Acute Quark Ingestion Increases Muscle Protein Synthesis Rates at Rest with a Further Increase after Exercise in Young and Older Adult Males in a Parallel-Group Intervention Trial

BackgroundIngestion of protein concentrates or isolates increases muscle protein synthesis rates in young and older adults. There is far less information available on the anabolic response following the ingestion of dairy wholefoods, which are commonly consumed in a normal diet. ObjectivesThis study investigates whether ingestion of 30 g protein provided as quark increases muscle protein synthesis rates at rest and whether muscle protein synthesis rates are further increased after resistance exercise in young and older adult males. MethodsIn this parallel-group intervention trial, 14 young (18–35 y) and 15 older (65–85 y) adult males ingested 30 g protein provided as quark after a single-legged bout of resistance exercise on leg press and leg extension machines. Primed, continuous intravenous L-[ring-13C6]-phenylalanine infusions were combined with the collection of blood and muscle tissue samples to assess postabsorptive and 4-h postprandial muscle protein synthesis rates at rest and during recovery from exercise. Data represent means ± SDs; η2 was used to measure the effect size. ResultsPlasma total amino acid and leucine concentrations increased after quark ingestion in both groups (both time: P < 0.001; η2 > 0.8), with no differences between groups (time × group: P = 0.127 and P = 0.172, respectively; η2<0.1). Muscle protein synthesis rates increased following quark ingestion at rest in both young (from 0.030 ± 0.011 to 0.051 ± 0.011 %·h−1) and older adult males (from 0.036 ± 0.011 to 0.062 ± 0.013 %·h−1), with a further increase in the exercised leg (to 0.071 ± 0.023 %·h−1 and to 0.078 ± 0.019 %·h−1, respectively; condition: P < 0.001; η2 = 0.716), with no differences between groups (condition × group: P = 0.747; η2 = 0.011). ConclusionsQuark ingestion increases muscle protein synthesis rates at rest with a further increase following exercise in both young and older adult males. The postprandial muscle protein synthetic response following quark ingestion does not differ between healthy young and older adult males when an ample amount of protein is ingested.This trial was registered at the Dutch Trial register, which is accessible via trialsearch.who.int www.trialregister.nl as NL8403.

Oral supplementation with yeast β-glucans improves the resolution of Escherichia coli-associated inflammatory responses independently of monocyte/macrophage immune training.

Confronted with the emerging threat of antimicrobial resistance, the development of alternative strategies to limit the use of antibiotics or potentiate their effect through synergy with the immune system is urgently needed. Many natural or synthetic biological response modifiers have been investigated in this context. Among them, β-glucans, a type of soluble or insoluble polysaccharide composed of a linear or branched string of glucose molecules produced by various cereals, bacteria, algae, and inferior (yeast) and superior fungi (mushrooms) have garnered interest in the scientific community, with not less than 10,000 publications over the last two decades. Various biological activities of β-glucans have been reported, such as anticancer, antidiabetic and immune-modulating effects. In vitro, yeast β-glucans are known to markedly increase cytokine secretion of monocytes/macrophages during a secondary challenge, a phenomenon called immune training. Here, we orally delivered β-glucans derived from the yeast S. cerevisiae to mice that were further challenged with Escherichia coli. β-glucan supplementation protected the mice from E. coli intraperitoneal and intra-mammary infections, as shown by a lower bacterial burden and greatly diminished tissue damage. Surprisingly, this was not associated with an increased local immune response. In addition, granulocyte recruitment was transient and limited, as well as local cytokine secretion, arguing for faster resolution of the inflammatory response. Furthermore, ex-vivo evaluation of monocytes/macrophages isolated or differentiated from β-glucan-supplemented mice showed these cells to lack a trained response versus those from control mice. In conclusion, dietary β-glucans can improve the outcome of Escherichia coli infections and dampen tissue damages associated to excessive inflammatory response. The mechanisms associated with such protection are not necessarily linked to immune system hyper-activation or immune training.

The Muscle Protein Synthetic Response to the Ingestion of a Plant-Derived Protein Blend Does Not Differ from an Equivalent Amount of Milk Protein in Healthy Young Males

Plant-derived proteins are considered to have lesser anabolic properties when compared with animal-derived proteins. The attenuated rise in muscle protein synthesis rates following ingestion of plant-derived compared with animal-derived protein has been, at least partly, attributed to deficiencies in specific amino acids such as leucine, lysine, and/or methionine. Combining different plant-derived proteins could provide plant-derived protein blends with a more balanced amino acid profile. This study aimed to compare postprandial muscle protein synthesis rates following the ingestion of 30g milk protein with a 30 g blend combining wheat, corn, and pea protein in healthy young men. In a randomized, double-blind, parallel-group design, 24 young males (aged 24±4 y) received a primed continuous l-[ring-13C6]-phenylalanine infusion after which they ingested 30g milk protein (MILK) or a 30 g plant-derived protein blend combining 15g wheat, 7.5g corn, and 7.5g pea protein (PLANT-BLEND). Blood and muscle biopsies were collected frequently for 5h to assess postprandial plasma amino acid profiles (secondary outcome) and subsequent muscle protein synthesis rates (primary outcome). Data were analyzed by 2-factor repeated measures ANOVA and 2-samples t tests. MILK increased plasma essential amino acid concentrations more than PLANT-BLEND over the 5 h postprandial period (incremental AUC = 151 ± 31compared with 79±12 mmol·300 min·L-1, respectively; P<0.001). Ingestion of both MILK and PLANT-BLEND increased myofibrillar protein synthesis rates (P<0.001), with no significant differences between treatments (0.053±0.013%/h and 0.064±0.016%/h, respectively; P=0.08). Ingestion of 30g plant-derived protein blend combining wheat-, corn-, and pea-derived protein increases muscle protein synthesis rates in healthy young males. The muscle protein synthetic response to the ingestion of 30g of this plant-derived protein blend does not differ from the ingestion of an equivalent amount of a high-quality animal-derived protein.Clinical trial registry number for Nederlands Trial Register: NTR6548 (https://trialsearch.who.int/Trial2.aspx?TrialID=NTR6548).

Flow of Casson Nanofluid Past a Permeable Surface: Effects of Brownian Motion, Thermophoretic Diffusion and Lorenz force

This study is aimed at testing the significance of Brownian movement and thermophoresis dispersion on MHD Casson nano liquid limit layer stream past a nonlinear slanted permeable extending surface, with the impact of convective limits and warm radiation with a synthetic response. Nonlinear ODEs are gotten from overseeing nonlinear PDEs by utilizing good comparability changes. The amounts related to building angles, for example, skin grating, Nusselt and Sherwood numbers alongside different effects of factors from the material on the speed and temperature, are outlined. Numerical consequences of the current investigation are acquired through the Runge-Kutta Fehlberg strategy alongside the shooting procedure and in a constraining sense are diminished to the distributed outcomes for a precision reason.

Data-Driven Direct Diagnosis of PV Connected Batteries

Photovoltaic systems are providing a growing share of power to the electric grid worldwide. As more and more of these systems are tied with battery energy storage to balance their intermittency, being able to ensure long and safe operation of these batteries will become critical. Because of their sporadic usage, far from the typical constant current or constant power, diagnosability without having to perform lengthy maintenance cycles will be a key factor to accelerate deployment.This work proposes a new methodology to enable the training of machine learning algorithms so they could be applied directly to photovoltaic (PV) battery charging data for opportunistic diagnosis. This is done by training the algorithms on synthetic voltage data under different degradations calculated from clear-sky model irradiance data. Validation was performed on synthetic voltage responses calculated from plane of array irradiance observations for a PV system located in Maui, HI, USA.Herein, we will present the result of our proof-of-concept study where we investigated the diagnosability of the voltage response of PV charged batteries under 18 different cloud coverages scenarios and for more than 10,000 different degradations. We also evaluated the effect of training conditions on clear-sky irradiance data by analyzing the resulting differences from training on 700,000 different voltage curves for a single day vs. 45,000 different voltage curves for of each of the 18 days used for cloud coverage estimation. In addition, we considered and quantified the effect of cell-to-cell variations. Training was performed on five state-of-the-art machine learning algorithms for battery diagnosis which included decision tree ensemble methods and neural networks. Finally, because the diagnosis was done outside of constant current, the capacity- and time-based information were decorrelated and compared. While time-base diagnosis is the most interesting for deployed systems, it was shown to be less accurate than its capacity counterpart for the tested algorithms. Yet, the accuracy of the diagnosis is still satisfactory for days where cloud effect is limited (average RMSE of 2.5% compared to 1.3% for capacity based if 50% or more clear skies).Summarizing, we will show that the degradation of PV-connected batteries could be diagnosed opportunistically without the need for maintenance cycles using well-trained state-of-art machine learning algorithms. Calculated RMSEs were below 2% for days with 50% or more clear skies considering more than 10,000 different degradation paths with 25% or less of the three thermodynamic degradation modes. In addition to the results themselves, and before real PV battery degradation data becomes available, this work is showing the significant benefits of using synthetic data to understand the expected variations and to start preparing adapted tools for when data become available.

Electromagnetic mixed convective flow and melting heat process of Sisko nanomaterial through non-linear expanding surface with thick dissemination and convective constrains: thermal case investigatory

This work explores the possessions of a condensed Sisko nanofluid’s MHD limit layer stream above a non-direct extended sheet, including the impact of liquefying heat move, synthetic response, thick dissemination, slip, and convective limit situation. Employing the shooting routine in conjunction with the Runge–Kutta-Fehlberg process, the intermediate differential conditions and limit circumstances that are administered are changed into a non-straight standard differential conditions procedure. The outcomes presume that the mass exchange rates increment, though heat move rates decline with thick dispersal for non-Newtonian liquids. Notwithstanding, the hotness move rates support radiation and dissolving boundaries.

Advanced adjustable sensor for multi-signal analysis via construction of co-continuous dual-sensing networks

Multifunctional sensors (MFS) have broad prospects in fields such as healthcare and environmental monitoring, which should integrate multi-signal detection. But the signal crosstalk problem limits the functional expansion of sensors, which is an urgent problem that few people have completely solved. We firstly propose to combine two matrices with different sensing function in a co-continuous network as a composite of ‘‘water channel’’ and elastic skeleton, to achieve the non-interfering integration of different sensing capabilities in multifunctional sensor. Then, through the study of multi-response law, a mathematical model is innovatively proposed to analyze the synthetic response signals and solve for monitoring signals. From the results, the MFS can maintain excellent mechanical properties while producing superior responses to the triple factors of temperature, humidity and mechanical stimuli. The mathematical model can accurately describe the synergistic effects of temperature and humidity, and the theoretical results are in good agreement with the actual results, which demonstrates the effectiveness of this strategy for discriminating multi-signal responses. Thus, the simple and effective fabricating concept and method for sensors are proposed with the construction of “water channel”, which can effectively distinguish temperature and humidity responses through two-phase co-continuous networks with different independent function and a mathematical model.

AVO study on a known geothermal reservoir located in the fractured carbonate formations of the pre-Cenozoic basement, Northwest Hungary

Amplitude Versus Offset (AVO) analysis has been successfully applied in the hydrocarbon industry for more than three decades. This effective tool of the joint seismic and well-log data processing enables to predict and analyze fluid saturated porous geological formations. AVO methodology is based on the anomalous behavior of the pre-stack reflected amplitudes observed from fluid bearing rocks. However, the potential of AVO methodology is still unexploited in geothermal exploration, although the lithology and rock physical properties are very similar. In this study, we summarize the theoretical backgrounds and calculate synthetic AVO responses of a known geothermal reservoir located in the fractured carbonates of the Mesozoic basement. We demonstrate that the AVO response of a deep geothermal reservoir can be quite different from the amplitude response observed from a hydrocarbon bearing clastic formation. AVO attributes of the investigated geothermal reservoir are presented, and the potential of its detection by seismic amplitude data are discussed.

Power System Inertia Dispatch Modelling in Future German Power Systems: A System Cost Evaluation

Increasing the share of grid frequency converter-connected renewables reduces power system inertia, which is crucial for grid frequency stability. However, this development is insufficiently covered by energy system modelling and analysis as well as related scientific literature. Additionally, only synchronous inertia from fossil fuel-emitting power plants is represented, although renewable generators are a source of synthetic inertia, thus resulting in increased must-run capacities, CO2 emissions and system costs. The work at hands adds an analysis of the future German power system considering sufficient inertia to the literature. Therefore, results of an novel open-source energy system model are analysed. The model depicts minimum system inertia constraints as well as wind turbines and battery storage systems as a carbon-dioxide-free source for a synthetic inertial response. Results indicate that integrating system inertia constraints in energy system models has a high impact on indicators such as system costs. Especially when investments in additional storage units providing an inertial response are necessary. With respect to researched scenarios, system cost increases range from 1% up to 23%. The incremental costs for providing additional inertia varies between 0.002 EURO/kg·m2 and 0.61 EURO/kg·m2.

Recalibration of low seismic excitations in Brazil through probabilistic and deterministic analyses: Application for shear buildings structures

AbstractBrazil has a low level of seismicity compared to several other regions in the world; however, some significant earthquakes occurred. In this article, four techniques have been used to define new seismic inputs: probabilistic seismic hazard, elastic spectra, synthetic spectra, and artificial accelerograms. To carry out the probabilistic analysis, new seismogenic zones for southeast Brazil established in 2018 have been implemented. Elastic response spectra follow the Brazilian code, whereas the synthetic response spectra have been defined by using attenuation equations. Finally, the artificial accelerograms have been developed using analytical models. Modified Brazilian elastic response spectra by considering the results of the probabilistic seismic hazard analyses are proposed. Artificial accelerations, consistent to the non‐modified and modified elastic response spectra, show that for non‐modified spectra the structural response increases of ~2.50 times. Data for seismogenic zones and specific analytical equations to obtain the probability of non‐exceedance of the spectral accelerations have been adapted for this study. An application for shear buildings was analyzed.

Tailored meshing for parallel 3D electromagnetic modeling using high-order edge elements

We present numerical experiments for geophysics electromagnetic (EM) modeling based upon high-order edge elements and supervised h+p refinement approaches on massively parallel computers. Our high-order h+p refinement strategy is based on and extends the PETGEM code. We focus on the performance study in terms of accuracy, convergence rate, and computational effort to solve real-life 3D setups based on synthetic and experimental data for energy reservoir characterization. These test cases show variable resolution discretization needs and realistic physical parameters. In general, our numerical results are consistent theoretically. The use of h-adapted meshes was efficient to achieve a certain accuracy level in the synthetic EM responses. Regarding global p-refinement, p=2 exhibits the best accuracy/performance trade-off. Selective p-refinement might offer a better compromise between accuracy and computational cost. However, for p-refinement at different entities, the best refinement scheme consists of using p=3 at the volume level with p=1 at faces and edges. Thus, p-refinement can be competitive if applied hierarchically. Nevertheless, we acknowledge that the performance of our supervised h+p refinement strategy depends on the input model (e.g., conductivity, frequency, domain decomposition strategy, among others). Whatever the chosen configuration, our numerical results provide an in-depth understanding of EM modeling’s pros and cons when supervised h+p refinement schemes are applied.

Brace yourself! Why managers should adopt a synthetic media incident response playbook in an age of falsity and synthetic media

Synthetic media presents looming threats to managers in a business setting. To address this issue, we first offer a short overview of the evolution of media manipulation to contextualize the new era of synthetic media. Then, we present the problems associated with synthetic media via veridicality and heuristics to illustrate how consumers have little choice but to believe what they see, read, and hear online. We outline the most likely and impactful types of synthetic media threats and attacks and present a synthetic media incident response playbook. Our aim is to inform managers about six specific phases so they can prepare, assess, detect, analyze, and recover from synthetic media incidents and coordinate their lessons learned.

Effects of PGC-1α overexpression on the myogenic response during skeletal muscle regeneration

The ability of skeletal muscle to regenerate from injury is crucial for locomotion, metabolic health, and quality of life. Peroxisome proliferator-activated receptor-γ coactivator-1α (PGC1A) is a transcriptional coactivator required for mitochondrial biogenesis. Increased mitochondrial biogenesis is associated with improved muscle cell differentiation, however PGC1A's role in skeletal muscle regeneration following damage requires further investigation. The purpose of this study was to investigate the role of skeletal muscle-specific PGC1A overexpression during regeneration following damage. 22 C57BL/6J (WT) and 26 PGC1A muscle transgenic (A1) mice were injected with either phosphate-buffered saline (PBS, uninjured control) or Bupivacaine (MAR, injured) into their tibialis anterior (TA) muscle to induce skeletal muscle damage. TA muscles were extracted 3- or 28-days post-injury and analyzed for markers of regenerative myogenesis and protein turnover. Pgc1a mRNA was ∼10–20 fold greater in A1 mice. Markers of protein synthesis, AKT and 4EBP1, displayed decreases in A1 mice compared to WT at both timepoints indicating a decreased protein synthetic response. Myod mRNA was ∼75% lower compared to WT 3 days post-injection. WT mice exhibited decreased cross-sectional area of the TA muscle at 28 days post-injection with bupivacaine compared to all other groups. PGC1A overexpression modifies the myogenic response during regeneration.

The Buongiorno model with Brownian and thermophoretic diffusion for MHD casson nanofluid over an inclined porous surface

The key goal of the study under concern is to test the effects of Brownian movement and thermophoresis dispersion on MHD Casson nanofluid limit layer stream over a nonlinear slanted permeable extending surface, with the impact of convective limits and warm radiation with synthetic response. Nonlinear ODEs are gotten from overseeing nonlinear PDEs by utilizing good comparability changes. The amounts related with building angles, for example, skin grating, Nusselt number and Sherwood number alongside different effects of material factors on the speed, temperature, and focus, are explained and explained with outlines. The numerical consequences of the current investigation are acquired through the Runge-Kutta Fehlberg strategy alongside shooting procedure and in constraining sense are diminished to the distributed outcomes for precision reason.&#x0D;

Mass transfer effects on mucus fluid in the presence of chemical reaction

The mucus fluid vehicle is impacted by the synthetic response that changes the physical science of liquid due to the thickness of the bodily fluid. Additionally, various issues in the respiratory system might happen because of bodily fluid adequacy. A central point of transportation of immunizations to forestall COVID-19 is the concentration level expected during movement, stockpiling, and dispersion. The current review stated that mucus fluid transportation is restrained through magnetic force originating due to heat variation. Permeable channel over respiratory disease and chemicals due to mass reaction–diffusion variation. The bodily fluid development is surveyed by the force, energy, and diffusion condition influence of body powers because of attractive field, source of heat cause of thermal conduction, resistance due to disease chemical reaction cause of concentration profile. The nonlinear arrangement of incomplete differential conditions is addressed by the Laplace transform technique, and MATLAB programming outcomes are initiated for momentum, temperature, and diffusion fields and inferred that the bodily fluid stream decelerates due to magnetic force. The skin friction, Nusselt number, Sherwood number, and the microorganism’s thickness are assessed and explained exhaustively. Furthermore, microorganisms are occupied in different elements to survey the mucus fluid mechanism.

Drone-mounted ground-penetrating radar surveying: Flight-height considerations for diffraction-based velocity analysis

Recent studies highlight the potential of the drone platform for ground-penetrating radar (GPR) surveying. Most guidance for optimizing drone flight heights is based on maximizing the image quality of target responses, but no study yet considers the impact on diffraction traveltimes. Strong GPR velocity contrasts across the air-ground interface introduce significant refraction effects that distort diffraction hyperbolas and introduce errors into diffraction-based velocity analysis. The severity of these errors is explored with synthetic GPR responses, using ray- and finite-difference approaches, and a field GPR data set acquired over a sequence of diffracting features buried up to 1 m depth. Throughout, GPR antennas with 1000 MHz center frequency are raised from the ground to heights &lt;0.9 m (i.e., 0–3 times the wavelength in air). Velocity estimates are within +10% of modeled values (spanning from 0.07 to 0.13 m/ns) if the antenna height is within 1/2 wavelength in air above the ground surface. Greater heights reduce diffraction curvature, damaging velocity precision, and masking diffractions against a background of subhorizontal reflectivity. Field data highlight further problems of the drone-based platform, with data dominated by reverberations in the air gap and reduced spatial resolution of wavelets at target depth. We suggest that a drone-based platform is unsuitable for diffraction-based velocity analysis, and any future drone surveys are benchmarked against ground-coupled data sets.

Abstract 5588: PD-1 blockade synergizes with IMiDs to enhance bispecific T cell engager immune responses to Vk*MYChCRBN multiple myeloma by preventing T cell exhaustion

Abstract Bispecific T cell engagers (TCE) are novel immunotherapies for cancer that redirect a synthetic immune response against tumors. Early clinical trial data show that BCMA-targeting TCEs are highly effective immunotherapies for treating relapsed and refractory multiple myeloma (MM). Thus, it is important to define combinatorial approaches that increase the efficacy and durability of TCE. We recently investigated a murine anti-BCMA TCE in the immunocompetent IMiD-sensitive Vk*MYChCRBN model of MM. Our data show that anti-BCMA TCE was safe and efficacious in most mice, but failed in those with high-tumor burden, consistent with clinical reports of TCE in leukemia. We tested the combination of anti-BCMA TCE and IMiDs to provide an additive anti-tumor effect and stimulatory cytokines, such as IL-2 in the tumor environment. This combination expanded cytolytic T cells and improved activity even in IMiD-resistant high-tumor burden cases. Yet, survival was only marginally extended due to T cell exhaustion. We hypothesized that blockade of the inhibitory immune checkpoint PD-1 would synergize with TCE and IMiDs to potentiate the response directed by the TCE by reinvigorating exhausted T cells. We evaluated the efficacy of the triple therapy combination in Vk*MYChCRBN: the anti-BCMA TCE, pomalidomide, and anti-PD1. Checkpoint blockade alone, or in combination with TCE did not improve tumor control or survival compared to control treatments. The triple combination proved most effective at controlling tumor growth, inducing a complete response after 2 weeks of treatment, and was curative in 40% of the mice. Longitudinal analysis of the immune response showed that the addition of anti-PD1 to TCE-IMiDs rescued T cell expansion at tumor sites and sustained expression of activation markers after repeated doses. Longitudinal analysis of blood and bone marrow (BM) cytokines showed the typical profile associated with cytokine release syndrome (CRS) during T cell immunotherapy. Of note, we observed IL-2, IFN-γ, and GM-CSF production was sustained in the BM tumor environment in the triple combination. We suspect that these cytokines, especially IL-2, are key to sustaining non-exhausted effector T cell proliferation in response to TCE therapy. Expectedly, we observed toxicity with the elevated cytokine release in the triple combination. that we anticipate could be controlled with step-up dosing or CRS mitigation treatment. We conclude that combination of PD1 blockade, IMiDs and TCE provides superior efficacy in the immunocompetent preclinical model of MM, Vk*MYChCRBN, while increasing inflammatory pathways that can lead to CRS. Finally, as we found this combination to be curative in some mice, we will investigate whether this combination immunotherapy also enhanced an endogenous anti-tumor immune response leading to protective immunosurveillance. Citation Format: Erin W. Meermeier, Seth J. Welsh, Meaghen Sharik, Megan T. Du, Chang-Xin Shi, Bryant Chau, Feng Wang, Matthew Wheeler, Natalie Bezman, Pavel Strop, P. Leif Bergsagel, Marta Chesi. PD-1 blockade synergizes with IMiDs to enhance bispecific T cell engager immune responses to Vk*MYChCRBN multiple myeloma by preventing T cell exhaustion [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5588.

Abstract 2593: Combined ATR+PARP inhibition exhibits potent synergy in colorectal and pancreatic cancer cytotoxicity

Abstract Precision medicine continues to expand treatment options for patients tailored to tumor phenotype. In homologous recombination (HR) deficient cancers like those with BRCA1/2-mutations, inhibition of poly (ADP-ribose) polymerase (PARP) has shown improved mortality compared to older gold standard therapies like DNA damaging agents. Unfortunately estimates upward of 40% of patients develop resistance to PARP inhibitor monotherapy during the course of their treatment. We explored potential synergistic drug combinations to re-sensitize tumors with acquired PARP inhibitor resistance in pancreatic and colorectal cancer. We hypothesized that dual inhibition of the DDR pathway through PARP and Ataxia telangiectasia and Rad3 related (ATR) inhibition would combine synergistically especially in cell lines with existing HR deficiencies through a synthetic lethality-mediated response. The ATR inhibitor Ceralasertib was selected for its potent antagonism of the DDR pathway, a key pathway associated with cell survival through DNA repair. Pancreatic and colorectal cell lines were carefully selected based on their varying mutational profiles to study differences in response to dual treatment. CellTiter-Glo® (CTG) was used after drug treatment to quantify IC-50. CTG synergy and combination indices were used to study drug combinations, and western blotting identified changes in protein expression among key mediators of cell survival and apoptosis. Colony forming assays and cytokine profiling using Luminex technology (and single cell cytokine profiling) were performed to study changes within the tumor microenvironment. We observed strong synergy and cytotoxicity in addition to increased apoptosis and cellular disassembly following treatment with dual ATR+PARP inhibition compared to monotherapy alone. Western Blot showed upregulation of cleaved PARP and cleaved Caspase 8 with combination therapy, and cytokine profiles provided insights into immune-suppressive versus stimulatory TME after drug treatment. There is potent synergy when ATR inhibitors are added to PARPi therapy in the context of pancreatic and colorectal cancers. Ongoing research efforts are further characterizing the mechanisms underlying these observed synergies in the same and additional tumor types such as prostate and ovarian cancer. Citation Format: Anna M. Ochsner, Kelsey E. Huntington, Lanlan Zhou, Benedito Carneiro, Wafik El-Deiry. Combined ATR+PARP inhibition exhibits potent synergy in colorectal and pancreatic cancer cytotoxicity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2593.

Investigation of functional near-infrared spectroscopy signal quality and development of the hemodynamic phase correlation signal.

.Significance: There is a longstanding recommendation within the field of fNIRS to use oxygenated () and deoxygenated (HHb) hemoglobin when analyzing and interpreting results. Despite this, many fNIRS studies do focus on only. Previous work has shown that on its own is susceptible to systemic interference and results may mostly reflect that rather than functional activation. Studies using both and HHb to draw their conclusions do so with varying methods and can lead to discrepancies between studies. The combination of and HHb has been recommended as a method to utilize both signals in analysis.Aim: We present the development of the hemodynamic phase correlation (HPC) signal to combine and HHb as recommended to utilize both signals in the analysis. We use synthetic and experimental data to evaluate how the HPC and current signals used for fNIRS analysis compare.Approach: About 18 synthetic datasets were formed using resting-state fNIRS data acquired from 16 channels over the frontal lobe. To simulate fNIRS data for a block-design task, we superimposed a synthetic task-related hemodynamic response to the resting state data. This data was used to develop an HPC-general linear model (GLM) framework. Experiments were conducted to investigate the performance of each signal at different SNR and to investigate the effect of false positives on the data. Performance was based on each signal’s mean -value across channels. Experimental data recorded from 128 participants across 134 channels during a finger-tapping task were used to investigate the performance of multiple signals [, HHb, HbT, HbD, correlation-based signal improvement (CBSI), and HPC] on real data. Signal performance was evaluated on its ability to localize activation to a specific region of interest.Results: Results from varying the SNR show that the HPC signal has the highest performance for high SNRs. The CBSI performed the best for medium-low SNR. The next analysis evaluated how false positives affect the signals. The analyses evaluating the effect of false positives showed that the HPC and CBSI signals reflect the effect of false positives on and HHb. The analysis of real experimental data revealed that the HPC and HHb signals provide localization to the primary motor cortex with the highest accuracy.Conclusions: We developed a new hemodynamic signal (HPC) with the potential to overcome the current limitations of using and HHb separately. Our results suggest that the HPC signal provides comparable accuracy to HHb to localize functional activation while at the same time being more robust against false positives.

Potato Protein Ingestion Increases Muscle Protein Synthesis Rates at Rest and during Recovery from Exercise in Humans.

ABSTRACTIntroductionPlant-derived proteins have received considerable attention as an alternative to animal-based proteins and are now frequently used in both plant-based diets and sports nutrition products. However, little information is available on the anabolic properties of potato-derived protein. This study compares muscle protein synthesis rates after the ingestion of 30 g potato protein versus 30 g milk protein at rest and during recovery from a single bout of resistance exercise in healthy, young males.MethodsIn a randomized, double-blind, parallel-group design, 24 healthy young males (24 ± 4 yr) received primed continuous l-[ring-13C6]-phenylalanine infusions while ingesting 30 g potato-derived protein or 30 g milk protein after a single bout of unilateral resistance exercise. Blood and muscle biopsies were collected for 5 h after protein ingestion to assess postprandial plasma amino acid profiles and mixed muscle protein synthesis rates at rest and during recovery from exercise.ResultsIngestion of both potato and milk protein increased mixed muscle protein synthesis rates when compared with basal postabsorptive values (from 0.020% ± 0.011% to 0.053% ± 0.017%·h−1 and from 0.021% ± 0.014% to 0.050% ± 0.012%·h−1, respectively; P < 0.001), with no differences between treatments (P = 0.54). In the exercised leg, mixed muscle protein synthesis rates increased to 0.069% ± 0.019% and 0.064% ± 0.015%·h−1 after ingesting potato and milk protein, respectively (P < 0.001), with no differences between treatments (P = 0.52). The muscle protein synthetic response was greater in the exercised compared with the resting leg (P < 0.05).ConclusionsIngestion of 30 g potato protein concentrate increases muscle protein synthesis rates at rest and during recovery from exercise in healthy, young males. Muscle protein synthesis rates after the ingestion of 30 g potato protein do not differ from rates observed after ingesting an equivalent amount of milk protein.