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Stochastic optimization of a district energy system (DES) is investigated with renewable energy systems integration and uncertainty analysis to meet all three major types of energy consumption: electricity, heating, and cooling. A district of buildings on the campus of the University of Utah is used as a case study for the analysis. The proposed DES incorporates solar photovoltaics (PV) and wind turbines for power generation along with using the existing electrical grid. A combined heat and power (CHP) system provides the DES with power generation and thermal energy for heating. Natural gas boilers supply the remaining heating demand and electricity is used to run all of the cooling equipment. A Monte Carlo study is used to analyze the stochastic power generation from the renewable energy resources in the DES. The optimization of the DES is performed with the Particle Swarm Optimization (PSO) algorithm based on a day-ahead model. The objective of the optimization is to minimize the operating cost of the DES. The results of the study suggest that the proposed DES can achieve operating cost reductions (approximately 10% reduction with respect to the current system). The uncertainty of energy loads and power generation from renewable energy resources heavily affects the operating cost. The statistical approach shows the potential to identify probable operating costs at different time periods, which can be useful for facility managers to evaluate the operating costs of their DES.

Simultaneous achievement of lightweight, ultrahigh strength, large fracture strain, and high damping capability is challenging because some of these mechanical properties are mutually exclusive. Here, we utilize self-assembled polymeric carbon precursor materials in combination with scalable nano-imprinting lithography to produce nanoporous carbon nanopillars. Remarkably, nanoporosity induced via sacrificial template significantly reduces the mass density of amorphous carbon to 0.66 ~ 0.82 g cm −3 while the yield and fracture strengths of nanoporous carbon nanopillars are higher than those of most engineering materials with the similar mass density. Moreover, these nanopillars display both elastic and plastic behavior with large fracture strain. A reversible part of the sp 2 -to-sp 3 transition produces large elastic strain and a high loss factor (up to 0.033) comparable to Ni-Ti shape memory alloys. The irreversible part of the sp 2 -to-sp 3 transition enables plastic deformation, leading to a large fracture strain of up to 35%. These findings are substantiated using simulation studies. None of the existing structural materials exhibit a comparable combination of mass density, strength, deformability, and damping capability. Hence, the results of this study illustrate the potential of both dense and nanoporous amorphous carbon materials as superior structural nanomaterials. Simultaneous achievement of lightweight and high strength is challenging. Here, authors combine self-assembly of nanoscale block copolymer and carbonization to create nanoporous amorphous carbon materials, which have the density of elastomers or plastic but the strength of metals or alloys.

The steroidal neurotoxin (-)-batrachotoxin functions as a potent agonist of voltagegated sodium ion channels (Navs). Here we report concise asymmetric syntheses of the natural (-) and non-natural (+) antipodes of batrachotoxin, as well both enantiomers of a C-20 benzoate-modified derivative. Electrophysiological characterization of these molecules against Nav subtypes establishes the non-natural toxin enantiomer as a reversible antagonist of channel function, markedly different in activity from (-)-batrachotoxin. Protein mutagenesis experiments implicate a shared binding side for the enantiomers in the inner pore cavity of Nav. These findings motivate and enable subsequent studies aimed at revealing how small molecules that target the channel inner pore modulate Nav dynamics.

A thorough knowledge and understanding of the structure–property relationship between thermal conductivity and C-fiber morphology is important to estimate the behavior of carbon fiber components, especially under thermal loading. In this paper, the thermal conductivities of different carbon fibers with varying tensile modulus were analyzed perpendicular and parallel to the fiber direction. Besides the measurement of carbon fiber reinforced polymers, we also measured the thermal conductivity of single carbon fibers directly. The measurements clearly proved that the thermal conductivity increased with the tensile modulus both in fiber and perpendicular direction. The increase is most pronounced in fiber direction. We ascribed the increase in tensile modules and thermal conductivity to increasing anisotropy resulting from the orientation of graphitic domains and microvoids. Graphical abstract

The efficacy of an antibody-drug conjugate (ADC) is dependent on the properties of its linker-payload which must remain stable while in systemic circulation but undergo efficient processing upon internalization into target cells. Here, we examine the stability of a non-cleavable Amino-PEG6-based linker bearing the monomethyl auristatin D (MMAD) payload site-specifically conjugated at multiple positions on an antibody. Enzymatic conjugation with transglutaminase allows us to create a stable amide linkage that remains intact across all tested conjugation sites on the antibody, and provides us with an opportunity to examine the stability of the auristatin payload itself. We report a position-dependent degradation of the C terminus of MMAD in rodent plasma that has a detrimental effect on its potency. The MMAD cleavage can be eliminated by either modifying the C terminus of the toxin, or by selection of conjugation site. Both approaches result in improved stability and potency in vitro and in vivo. Furthermore, we show that the MMAD metabolism in mouse plasma is likely mediated by a serine-based hydrolase, appears much less pronounced in rat, and was not detected in cynomolgus monkey or human plasma. Clarifying these species differences and controlling toxin degradation to optimize ADC stability in rodents is essential to make the best ADC selection from preclinical models. The data presented here demonstrate that site selection and toxin susceptibility to mouse plasma degradation are important considerations in the design of non-cleavable ADCs, and further highlight the benefits of site-specific conjugation methods.

Background Glucagon-like peptide-1 (GLP-1) receptor agonists have metabolic and hepatic benefits in metabolic dysfunction–associated steatotic liver disease (MASLD), but their additive benefit compared to lifestyle modification only in real-world settings remains uncertain. This study compared the effects of GLP-1 agonist therapy and physical activity on body mass index (BMI) and noninvasive liver metrics in a predominantly Hispanic clinical population with MASLD. Methods This is a retrospective longitudinal study of 202 adults with MASLD evaluated at an outpatient gastroenterology clinic. BMI, controlled attenuation parameter (CAP), liver stiffness (kPa), and Fibrosis-4 (FIB-4) indices were analyzed at baseline and follow-up (1–2 years). Primary analyses compared follow up outcomes between GLP-1 therapy and an unmonitored physical activity comparator group; exploratory analyses assessed whether effects differed by sex or ethnicity. Results Among 193 patients with complete BMI data and 131 with liver metrics, GLP-1 agonist therapy was associated with a greater reduction in BMI (–1.47 kg/m²; 95% CI, − 2.54 to − 0.41; p  = 0.007) and in FIB-4 indices (–0.29; 95% CI, − 0.56 to − 0.03; p  = 0.029) compared with physical activity only. Adjusted differences in CAP (–3.31 dB/m) and liver stiffness (+ 0.01 kPa) were not statistically significant. Conclusion In this real-world MASLD cohort, GLP-1 therapy was associated with greater baseline-adjusted improvements in BMI and FIB-4 compared with physical activity alone, while CAP and liver stiffness were not statistically significant. These findings provide supportive real-world evidence for GLP-1 associated metabolic benefit and warrant confirmation of hepatic effects in larger prospective studies, including cohorts with substantial Hispanic representation.

Abstract Background Waning measles immunity among vaccinated individuals may result in an attenuated illness. This study compares the epidemiological, clinical, and laboratory profile of measles cases with waning immunity with other measles cases. Methods Polymerase chain reaction–positive (+) measles cases notified to Victoria’s Department of Health and Human Services from 2008 to 2017 with immunoglobulin (Ig) M and IgG tested at diagnosis were classified according to serology at diagnosis: IgG negative (−) (nonimmune), IgM+/IgG+ (indeterminate), or IgM−/IgG+ (waning immunity). Results Between 2008 and 2017, 297 measles cases were notified, of whom 190 (64%) were included; 151 of 190 (79%) were nonimmune at diagnosis, 26 (14%) were indeterminate, and 13 (7%) had waning immunity. Between 2008–2013 and 2014–2017, the proportion of cases with waning immunity increased from 0 of 87 (0%) to 13 of 103 (13%) (P < .001) and the diagnostic sensitivity of initial IgM fell from 93% to 81% (P = .012), respectively. Seven (54%) waning immunity cases reported receiving measles-containing vaccines; 1 case had 2 documented doses. Compared with nonimmune and indeterminate cases, waning immunity cases were more likely to be male; less likely to report fever, coryza, and cough; and had lower burden of virus (higher cycle threshold values). Waning immunity cases had higher IgG titers than indeterminate cases (mean optical density values, 1.96 vs 0.71; P = .004). Onward transmission from 1 waning immunity case was documented. Conclusions Waning immunity among measles cases, associated with secondary vaccine failure and modified clinical illness, is emerging in Victoria with transmission potential. Between 2008 and 2018 an increase in IgM−/IgG+ measles cases was observed in Victoria, Australia. The 13 cases identified were commonly vaccinated men with attenuated illnesses, low viral loads, and high IgG titers. Onward transmission was documented from 1 case.

Smart, responsive materials are required in various advanced applications ranging from anti‐counterfeiting to autonomous sensing. Colloidal crystals are a versatile material class for optically based sensing applications owing to their photonic stopband. A careful combination of materials synthesis and colloidal mesostructure rendered such systems helpful in responding to stimuli such as gases, humidity, or temperature. Here, an approach is demonstrated to simultaneously and independently measure the time and temperature solely based on the inherent material properties of complex colloidal crystal mixtures. An array of colloidal crystals, each featuring unique film formation kinetics, is fabricated. Combined with machine learning‐enabled image analysis, the colloidal crystal arrays can autonomously record isothermal heating events — readout proceeds by acquiring photographs of the applied sensor using a standard smartphone camera. The concept shows how the progressing use of machine learning in materials science has the potential to allow non‐classical forms of data acquisition and evaluation. This can provide novel insights into multiparameter systems and simplify applications of novel materials. The optical response of multicomponent photonic crystals contains intricate information regarding a sample's thermal history. In this work, a reproducible sensor fabrication method coupled with fast data acquisition via digital photography is presented. Machine learning assisted evaluation allows smartphone‐based sensing of thermal events. Time and temperature can thereby be obtained independently and without specialized equipment.

The epidemiology of gastrointestinal stromal tumor has not been well examined, and prior studies often provide conflicting results. We conducted the first population-based study to evaluate the incidence and survival of malignant gastrointestinal stromal tumor in the United States. We utilized the Surveillance, Epidemiology, and End Results registry from the National Cancer Institute to identify all cases of malignant gastrointestinal stromal tumor diagnosed from 1992 to 2000. The age-adjusted incidence rates and the survival rates were calculated. Cox proportional hazards models were used to examine the risk of mortality. Between 1992 and 2000, there were 1,458 cases of diagnosed gastrointestinal stromal tumor. The age-adjusted yearly incidence rate was 0.68/100,000. The mean age at diagnosis was 63 yr. Fifty-four percent were men and 46% were women. The incidence rate was higher among men and among Blacks. Fifty-one percent of cases were in the stomach, 36% small intestine, 7% colon, 5% rectum, and 1% in the esophagus. Fifty-three percent of cases were staged as localized, 19% regional, 23% distant, and 5% unstaged. The 1- and 5-yr relative survival rates were 80% and 45%, respectively. The Cox analysis showed that older age, Black race, advanced stage, and receipt of therapy were independent predictors of mortality. Malignant gastrointestinal stromal tumors rare, but are more common in the older population, men, and Blacks. Risk factors for mortality include older age, Black race, advanced stage, and no surgical intervention.