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Redox potential is a solution property that influences specific yeast and bacterial activities and the rate of fermentation completion. There is a need to control it if reproducible fermentation outcomes are to be achieved and reliable conclusions are drawn at both the research and commercial scale of wine fermentation. Desirable outcomes that have been observed so far in wine fermentation include the prevention of sluggish and incomplete fermentations, an enhancement in cell viability, increases in the maintenance rate of non-growing cells, and the avoidance of hydrogen sulfide formation when elemental sulfur is present. Other expected fermentation outcomes include changes in the ratios of glycerol and succinate to ethanol, certain aroma and flavor components, and sulfite formation from sulfate in the juice. The juice composition determines the redox potential’s initial value, and the yeast strain’s interaction with the changing juice composition determines the pattern of the potential during fermentation. This interaction also establishes the dynamic response of the prevailing redox buffer to disturbances and the ability to control the potential during fermentation. The chemical reaction sequence, entities, and speciation thought to be responsible for establishing the redox potential in juices and wine are described. A quantitative model for control purposes remains elusive. Examples of the role of added iron in juice, different yeast strains, ambient light, and the addition of external hydrogen peroxide on the response of the potential are presented. Recent examples of controlling the redox potential during white wine and red wine fermentation at a commercial scale are presented, and areas for future research are identified.

The adoption of sensors to monitor wine fermentation enables the collection of large datasets that relate the initial juice chemistry, density and temperature patterns during fermentation to fermentation outcomes. Wine kinetic models are now being applied to commercial fermentations in real time to identify abnormal or sluggish fermentations. In this work, 222 red wine fermentations from five harvests at two commercial wineries were evaluated by a wine fermentation model. The model parameters, initial juice chemistries and fermentation outcomes were analyzed for trends and relationships between them. While the fermentations with higher initial assimilable nitrogen concentrations had higher maximum fermentation rates, this did not guarantee successful fermentation outcomes in the tailing stage of the fermentation. Neither the initial, final, minimum and maximum temperatures, nor the initial pH, titratable acidity, measured yeast-assimilable nitrogen and primary amino nitrogen concentrations had any significant correlation with the maximum fermentation rate or successful completion of the fermentation. These results suggest that the initial juice-assimilable nitrogen measurements for these juices are of limited use in predicting slower and incomplete fermentation outcomes.

The estimation of parameters in a wine fermentation model provides the opportunity to predict the rate and concentration outcomes, to strategically intervene to change the conditions, and to forecast the rates of heat and carbon dioxide release. The chosen parameters of the fermentation model are the initial assimilable nitrogen concentration and yeast properties (lag time, viability constant, and specific maintenance rate). This work evaluates six methods for parameter estimation: Bard, Bayesian Optimization, Particle Swarm Optimization, Differential Evolution, Genetic Evolution, and a modified Direct Grid Search technique. The benefits and drawbacks of the parameter computational methods are discussed, as well as a comparison of numerical integration methods (Euler, Runge–Kutta, backward differential formula (BDF), and Adams/BDF). A test set of density-time data for five white and five red commercial wine fermentations across vintage, grape cultivar, fermentation temperature, inoculated yeast strain, and fermentor size was used to evaluate the parameter estimation methods. A Canonical Variate Analysis shows that the estimation methods are not significantly different from each other while, in the parameter space, each of the fermentations were significantly different from each other.

This work develops microgrid dispatch algorithms with a unified approach to model predictive control (MPC) to (a) operate in grid-connected mode to minimize total operational cost, (b) operate in islanded mode to maximize resilience during a utility outage, and (c) utilize weighting factors in the grid-connected objective function to preserve islanded capability (on-site fuel reserves, battery state of charge) to enhance resilience in the potential event of an unplanned grid outage. Resilience is defined using microgrid survivability (probability to serve 100% of critical load), autonomy (duration of time to serve 100% of critical load), and unserved energy (curtailed critical load) for a target of 7 days during a grid outage. The developed methods are applied to a military microgrid with 2,250 kW of diesel generation, 3,450 kW/13,800 kWh battery storage, and 16,479 kW of solar photovoltaics. Sensitivity analysis is conducted to determine the selection of weighting factors to have the best impact on three developed objectives: grid-connected economics, islanded resilience, and carbon intensity. Optimal weighting factors reduce operating costs by 0.1%, increase survivability by 3.9%, increase autonomy by 16.7%, reduce unserved energy by 94.1%, and increase carbon intensity by 2.5%.

The ability to model the kinetics of wine fermentation enables the early detection of abnormal, sluggish or stuck fermentations, and the prediction of present and future rates of energy, CO2 and ethanol vapor release. While several wine fermentation models have been published, there are only a few that have been successfully adopted for commercial practice. In this work, the mathematical descriptions of wine fermentation are reviewed and compared. The common features of these include descriptions for the kinetics of yeast growth; substrate and nutrient consumption; product formation; and total and viable cell mass. Additional features include the inhibition of growth by ethanol; competitive inhibition of glucose and fructose uptake; glycerol formation; and the calculation of density from solution composition and solute properties. Three models were selected to compare their ability to describe the sugar, ethanol, biomass and nitrogen of benchtop fermentations at four temperatures, previously published. The models are assessed for their goodness of fit to the data in synthetic-medium fermentations and their suitability for analyzing and predicting commercial wine fermentations.

B cells contribute to multiple aspects of autoimmune disorders, and B cell–targeting therapies, including B cell depletion, have been proven to be efficacious in treatment of multiple autoimmune diseases. However, the development of novel therapies targeting B cells with higher efficacy and a nondepleting mechanism of action is highly desirable. Here we describe a nondepleting, high-affinity anti–human CD19 antibody LY3541860 that exhibits potent B cell inhibitory activities. LY3541860 inhibits B cell activation, proliferation, and differentiation of primary human B cells with high potency. LY3541860 also inhibits human B cell activities in vivo in humanized mice. Similarly, our potent anti-mCD19 antibody also demonstrates improved efficacy over CD20 B cell depletion therapy in multiple B cell–dependent autoimmune disease models. Our data indicate that anti-CD19 antibody is a highly potent B cell inhibitor that may have potential to demonstrate improved efficacy over currently available B cell–targeting therapies in treatment of autoimmune conditions without causing B cell depletion.

Most wine fermentations are completed in successive batches during a 2 month harvest period. Red wine fermentations are usually completed in 10 to 14 days, while white wine fermentations are completed in 21 to 24 days. The demand for resources—equipment, water, energy, labor, etc.—in a short time motivates the precise, automated control of the fermentation process. While the effects of temperature on wine chemistry are well studied, few advanced control strategies have been developed for the precise control of temperature for wine chemistry research. In this study, a nonlinear model predictive controller (NMPC) was developed to determine the temperature to achieve the desired fermentation rate. The controller was combined with a pulse cooling and heating strategy to improve the energy efficiency of temperature control. The feasibility of this approach is demonstrated by simulations and experiments in 15 L fermentations.

Energy conservation in microorganisms is classically categorized into respiration and fermentation; however, recent work shows some species can use mixed or alternative bioenergetic strategies. We explored the use of extracellular electron transfer for energy conservation in diverse lactic acid bacteria (LAB), microorganisms that mainly rely on fermentative metabolism and are important in food fermentations. The LAB Lactiplantibacillus plantarum uses extracellular electron transfer to increase its NAD+/NADH ratio, generate more ATP through substrate-level phosphorylation, and accumulate biomass more rapidly. This novel, hybrid metabolism is dependent on a type-II NADH dehydrogenase (Ndh2) and conditionally requires a flavin-binding extracellular lipoprotein (PplA) under laboratory conditions. It confers increased fermentation product yield, metabolic flux, and environmental acidification in laboratory media and during kale juice fermentation. The discovery of a single pathway that simultaneously blends features of fermentation and respiration in a primarily fermentative microorganism expands our knowledge of energy conservation and provides immediate biotechnology applications.

Combined with real-time monitoring of density and temperature, the control of the redox potential provides a new approach to influencing cell metabolism during growth, cell viability and non-growing yeast activity in wine fermentations. Prior research indicates that the problem of sluggish and incomplete fermentation can be alleviated by maintaining a constant redox potential during the ethanol fermentation. A secondary trait of hydrogen sulfide formation from elemental sulfur also seems to be associated with the development of low redox potentials during fermentation and this might be prevented by the deliberate control of redox potentials in a certain range. While the control of the redox potential during wine fermentations has been demonstrated previously at the research scale (100 L), the ability to control it in larger volumes typically seen in commercial conditions remained unanswered. Wine fermentations from the same load of Cabernet Sauvignon grapes from the 2021 harvest were conducted at three volumes: 100 L and 1500 L in a research winery and 10,000 L in a commercial winery. Using only pulses of air delivery, the redox potential was successfully controlled to −40 mV referenced to a silver/silver chloride electrode throughout the fermentations, at all scales. This appears to be the first published result of a controlled fermentation trial that includes the commercial scale and demonstrates the scalability of control of redox potential in wine fermentations.

Abstract Bergmann's rule predicts that organisms at higher latitudes are larger than ones at lower latitudes. Here, we examine the body size pattern of the Atlantic marsh fiddler crab, Minuca pugnax (formerly Uca pugnax), from salt marshes on the east coast of the United States across 12 degrees of latitude. We found that M. pugnax followed Bergmann's rule and that, on average, crab carapace width increased by 0.5 mm per degree of latitude. Minuca pugnax body size also followed the temperature–size rule with body size inversely related to mean water temperature. Because an organism's size influences its impact on an ecosystem, and M. pugnax is an ecosystem engineer that affects marsh functioning, the larger crabs at higher latitudes may have greater per‐capita impacts on salt marshes than the smaller crabs at lower latitudes.

Canagliflozin (Cana) is an FDA-approved diabetes drug that protects against cardiovascular and kidney diseases. It also inhibits the sodium glucose transporter 2 by blocking renal reuptake and intestinal absorption of glucose. In the context of the mouse Interventions Testing Program, genetically heterogeneous mice were given chow containing Cana at 180 ppm at 7 months of age until their death. Cana extended median survival of male mice by 14%. Cana also increased by 9% the age for 90th percentile survival, with parallel effects seen at each of 3 test sites. Neither the distribution of inferred cause of death nor incidental pathology findings at end-of-life necropsies were altered by Cana. Moreover, although no life span benefits were seen in female mice, Cana led to lower fasting glucose and improved glucose tolerance in both sexes, diminishing fat mass in females only. Therefore, the life span benefit of Cana is likely to reflect blunting of peak glucose levels, because similar longevity effects are seen in male mice given acarbose, a diabetes drug that blocks glucose surges through a distinct mechanism, i.e., slowing breakdown of carbohydrate in the intestine. Interventions that control daily peak glucose levels deserve attention as possible preventive medicines to protect from a wide range of late-life neoplastic and degenerative diseases.

Impacts of a warming climate are amplified in the Arctic. One notorious impact is recent and record-breaking summertime sea-ice loss. Expanding areas of open water and a prolonged ice-free season create opportunity for some industries but challenge indigenous peoples relying on sea ice for transportation and access to food. The observed and projected increase of Arctic maritime activity requires accurate sea-ice forecasts to protect life, environment, and property. Motivated by emerging prediction needs on the operational timescale (≤10 days), this study explores where local indigenous knowledge (LIK) fits into the forecaster toolbox and how it can be woven into useful sea-ice information products. The 2011 spring ice retreat season in the Bering Sea is presented as a forecasting case study. LIK, housed in a database of community-based ice and weather logs, and an ice-ocean forecast model developed by the US Navy are analyzed for their ability to provide information relevant to stakeholder needs. Additionally, metrics for verifying numerical sea-ice forecasts on multiple scales are derived. The model exhibits skill relative to persistence and climatology on the regional scale. At the community scale, we discuss how LIK and new model guidance can enhance public sea-ice information resources.

Real-time process metrics are standard for the majority of fermentation-based industries but have not been widely adopted by the wine industry. In this study, replicate fermentations were conducted with temperature as the main process parameter and assessed via in-line Oxidation Reduction Potential (ORP) probes and at-line profiling of phenolics compounds by UV-Vis spectroscopy. The California and Oregon vineyards used in this study displayed consistent vinification outcomes over five vintages and are representative of sites producing faster- and slower-fermenting musts. The selected sites have been previously characterized by fermentation kinetics, elemental profile, phenolics, and sensory analysis. ORP probes were integrated into individual fermentors to record how ORP changed throughout the fermentation process. The ORP profiles generally followed expected trends with deviations revealing previously undetectable process differences between sites and replicates. Site-specific differences were also observed in phenolic and anthocyanin extraction. Elemental composition was also analyzed for each vineyard, revealing distinctive profiles that correlated with the fermentation kinetics and may influence the redox status of these wines. The rapid ORP responses observed related to winemaking decisions and yeast activity suggest ORP is a useful process parameter that should be tracked in addition to Brix, temperature, and phenolics extraction for monitoring fermentations.

OBJECTIVE:The aim of the present study is to determine if CEACAM6 can be detected in the bile of patients with biliary cancer and can serve as a diagnostic biomarker for cholangiocarcinoma. SUMMARY BACKGROUND DATA:Distinguishing bile duct carcinoma from other diagnoses is often difficult using endoscopic or percutaneous techniques. The cell surface protein CEACAM6 is over-expressed in many gastrointestinal cancers and may be selectively elevated in biliary adenocarcinoma. METHODS:Bile from patients with benign biliary disease and cholangiocarcinoma (hilar, intrahepatic and distal) was collected at the time of index operation. The concentration of CEACAM6 was quantified by sandwich enzyme-linked immunosorbent assay (ELISA) and correlated to pathologic diagnosis. Diagnostic capability of CEACAM6 was evaluated by Wilcoxon rank-sum, linear regression, multiple regression, and receiver operating characteristic (ROC) curve analysis. RESULTS:Bile from 83 patients was analyzed: 42 with benign disease and 41 with cholangiocarcinoma. Patients in the benign cohort were younger, predominantly female, and had lower median biliary CEACAM6 levels than patients in the malignant cohort (7.5 ng/ml vs. 40 ng/ml; p = 14 ng/ml associated with 87.5% sensitivity, 69.1% specificity, and a likelihood ratio of 2.8 (AUC 0.74). Multiple regression analysis suggested elevated alkaline phosphatase and the presence of biliary endoprostheses may influence CEACAM6 levels. CONCLUSION:Biliary CEACAM6 can identify patients with extrahepatic cholangiocarcinoma with a high degree of sensitivity and should be investigated further as a potential screening tool.

El artículo se ocupa de una traducción castellana de los Dialoghi d'amore de Yehudah Abarbanel o León Hebreo, el ms. Or. Gaster 10688, en castellano aljamiado, que se halla en la British Library. Este texto es puesto en relación con las demás traducciones realizadas a lo largo del siglo XVI y con la tradición manuscrita italiana. El objetivo es demostrar que la traducción fue realizada a partir de una edición italiana de la obra y que no constituye, como algunos estudiosos habían supuesto, una obra original, pues coincide con la primera traducción castellana impresa, publicada en Venecia en 1568. Así mismo, se sitúa el manuscrito en el contexto de la producción literaria de las comunidades sefardíes radicadas en Levante en el siglo XVI.

The article deals with lists of objects which belonged to an important Portuguese banker in Rome, Antonio da Fonseca. The inventories, compiled some months before his death in February 1588, reveal a man of refined tastes and interests. In particular they indicate an abundance of objects of oriental provenance which can be deemed exotic, bezoar stones and some supposedly made from unicorn horns. The items contained in his home reflect his interests and activities as a prominent Portuguese merchant banker, linked to an empire which extended itself to the orient, to Africa, and the Indian Ocean.

Cost-effective energy storage is a critical enabler for the large-scale deployment of renewable electricity. Significant resources have been directed toward developing cost-effective energy storage, with research and development efforts dominated by work on lithium ion (Li-ion) battery technology. Though Li-ion batteries have many attractive qualities, it is not clear whether they can provide an affordable levelized cost of storage (LCOS) for certain applications, such as buildings. Buildings consume most of the world's electricity, and as much as 50% of their consumption goes toward meeting thermal loads. Thermal energy storage (TES) can provide a cost-effective alternative to Li-ion batteries for buildings; however, two questions remain to be answered. First, how much of total building energy storage requirements can be met via thermal storage for building loads? Second, can the LCOS for TES be favorable compared with Li-ion batteries? In this perspective, using the United States as a case study, we show that the total requirement for TES in buildings is in the range of ∼1200-4500 electrical GW h, depending on the fraction of solar versus wind in the generation mix. Furthermore, we show that with at least 25% wind generation, all of the storage needed by buildings to support the grid can be met by TES. We also introduce a framework to calculate LCOS for on-site TES in buildings to enable a direct comparison with electrical storage technologies such as Li-ion batteries. This is not trivial, because the input energy type for TES (electricity) differs from the output energy type (thermal energy), and the efficiency can depend on ambient conditions. Our LCOS analysis shows that in many situations, TES can be more cost-effective for buildings than Li-ion batteries. We conclude our perspective by discussing future research and development opportunities that can significantly advance the deployment of TES for buildings to help enable a renewable electricity-dependent grid.