Mutagenesis provides insight into proteins, but only recently have assays that couple genotype to phenotype been used to assess the activities of as many as 1 million mutant versions of a protein in ...a single experiment. This approach-'deep mutational scanning'-yields large-scale data sets that can reveal intrinsic protein properties, protein behavior within cells and the consequences of human genetic variation. Deep mutational scanning is transforming the study of proteins, but many challenges must be tackled for it to fulfill its promise.
•Designed and developed the battery thermal testing system.•Developed ECT model using ANSYS Fluent.•Studied the temperature and voltage profile at different discharge rates.•Validated the model with ...the experimental data.
Study of thermal performance in lithium-ion battery cell is crucial which directly affects the safety. Even though the operation of a lithium-ion battery cell is transient phenomena in most cases, most available thermal models for lithium-ion battery cell predicts only steady-state temperature fields. This paper presents a mathematical model to predict the transient temperature and voltage distributions of 18650 cylindrical lithium-ion battery at different discharge rates. For this, the 18650 cylindrical lithium-ion battery cell is tested inside the lab with an air-cooling method by four thermocouples mounted on the battery surface under four constant current discharge rates of 1 C, 2 C, 3 C, and 4 C in order to provide quantitative data regarding thermal behavior of lithium-ion batteries. Later, the numerical model is developed using ANSYS CFD software and it is found that the model predictions are in good agreement with experimental data for temperature and voltage profiles. The highest temperature is 46.86 °C at 4 C discharge rate as obtained from simulation. The results also show that the increased C-rates results in increased temperature on the principle surface of the battery.
Cytoskeletal structures characterized by actin filaments with uniform lengths, including the thin filaments of striated muscles and the spectrin-based membrane skeleton, use barbed and pointed-end ...capping proteins to control subunit addition/dissociation at filament ends. While several proteins cap the barbed end, tropomodulins (Tmods), a family of four closely related isoforms in vertebrates, are the only proteins known to specifically cap the pointed end. Tmods are ∼350 amino acids in length, and comprise alternating tropomyosin- and actin-binding sites (TMBS1, ABS1, TMBS2, and ABS2). Leiomodins (Lmods) are related in sequence to Tmods, but display important differences, including most notably the lack of TMBS2 and the presence of a C-terminal extension featuring a proline-rich domain and an actin-binding WASP-Homology 2 domain. The Lmod subfamily comprises three somewhat divergent isoforms expressed predominantly in muscle cells. Biochemically, Lmods differ from Tmods, acting as powerful nucleators of actin polymerization, not capping proteins. Structurally, Lmods and Tmods display crucial differences that correlate well with their different biochemical activities. Physiologically, loss of Lmods in striated muscle results in cardiomyopathy or nemaline myopathy, whereas complete loss of Tmods leads to failure of myofibril assembly and developmental defects. Yet, interpretation of some of the in vivo data has led to the idea that Tmods and Lmods are interchangeable or, at best, different variants of two subfamilies of pointed-end capping proteins. Here, we review and contrast the existing literature on Tmods and Lmods, and propose a model of Lmod function that attempts to reconcile the in vitro and in vivo data, whereby Lmods nucleate actin filaments that are subsequently capped by Tmods during sarcomere assembly, turnover, and repair.
Administration of substances directly into the cerebrospinal fluid (CSF) that surrounds the brain and spinal cord is one approach that can circumvent the blood-brain barrier to enable drug delivery ...to the central nervous system (CNS). However, molecules that have been administered by intrathecal injection, which includes intraventricular, intracisternal, or lumbar locations, encounter new barriers within the subarachnoid space. These barriers include relatively high rates of turnover as CSF clears and potentially inadequate delivery to tissue or cellular targets. Nanomedicine could offer a solution. In contrast to the fate of freely administered drugs, nanomedicine systems can navigate the subarachnoid space to sustain delivery of therapeutic molecules, genes, and imaging agents within the CNS. Some evidence suggests that certain nanomedicine agents can reach the parenchyma following intrathecal administration. Here, we will address the preclinical and clinical use of intrathecal nanomedicine, including nanoparticles, microparticles, dendrimers, micelles, liposomes, polyplexes, and other colloidalal materials that function to alter the distribution of molecules in tissue. Our review forms a foundational understanding of drug delivery to the CSF that can be built upon to better engineer nanomedicine for intrathecal treatment of disease.
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A pack level passive thermal management system has been designed, developed and experimentally investigated using a phase change composite material. Three 20Ah capacity LiFePO4 prismatic cells ...connected in series are used to form the battery pack and phase change composite material of different thicknesses are tested. The battery pack has been charged at 1C and discharged at 1C, 2C, 3C and 4C. A total of 18 thermocouples are used to measure the temperature at the principal surface of all three cells. The results obtained with the phase change composite material are compared with no cooling and liquid cooling options. The results show that, with the use of 6mm thick phase change composite material plates, the battery surface temperature reduces from 56.5°C at no cooling to 36.5°C at a 4C discharge rate. Even at a 1C discharge rate, the temperature of the battery pack drops from 33.5°C with no cooling to 29.1°C with phase change material plates. It is also observed that the effect of an increase in phase change material thickness on the battery pack temperature is insignificant beyond a 6mm thick plate. The results show that the temperature gradient is significantly lower with phase change composite material compared to no cooling and liquid cooling.
•Design of battery thermal management system with water cooling for LFP battery.•Design of mini-channel cold plates in NX and meshing in ICEM-CFD.•ANSYS CFD modeling of mini channel cold ...plates.•Temperature and velocity contours are obtained at different discharge rates and boundary conditions.•Results may contribute towards thermal safety of Lithium-ion batteries.
This paper has presented a comparative study of the temperature and velocity distributions within the mini-channel cold plates placed on a prismatic lithium-ion battery cell using experimental and numerical techniques. The study was conducted for water cooling methods at 1C and 2C discharge rates and different operating temperatures of 5°C, 15°C, and 25°C. A total of nineteen thermocouples were used for this experimental work, and were purposefully placed at different locations. Out of nineteen, ten T-type thermocouples were placed on the principal surface of the battery, and four K-type thermocouples were used to measure water inlet and outlet temperature. Computationally, the k-ε model in ANSYS Fluent was used to simulate the flow in a mini-channel cold plate, and the data was validated with the experimental data for temperature profiles. The present results show that increased discharge rates and increased operating temperature results in increased temperature of the cold plates. Furthermore, the thermocouple sensors nearest the electrodes (anode and cathode) measured the higher temperatures than the sensors located at the center of the battery surface.
Battery management system (BMS) requires an accurate prediction the remaining energy level or state of charge (SOC) of the cell or battery pack. However, in electric vehicles, batteries experience a ...dynamic operational environment whereby the simple algorithms employed in the portable devices to predict SOC, such as coulomb counting, are insufficient for this purpose. To address this problem, a Kalman filtering method is used to estimate the state of the charge of two different commercial lithium-ion batteries, with new physical insight being provided through an analysis of the Kalman filter covariance noise parameters. For example, the effect of geometry of the battery on value of these parameters is discussed. Different models are developed, tested and incorporated in the filter design. Subsequently, two types of Kalman filters including the extended Kalman filter and dual extended Kalman filter are implemented in order to predict the state of charge of the batteries. It is shown that the Kalman filtering can predict state of the charge of the battery with maximum 4% error.
•We model the dynamical behavior of the Li-ion batteries.•We use two types of Kalman filtering include extended and dual extended.•Two different geometries (cylindrical and prismatic) for batteries are considered.•The SOC of the batteries in a dynamical environment is accurately predicted.•New physical insights are provided through analysis of the Kalman filter parameters.
Multiplex assays of variant effect (MAVEs), such as deep mutational scans and massively parallel reporter assays, test thousands of sequence variants in a single experiment. Despite the importance of ...MAVE data for basic and clinical research, there is no standard resource for their discovery and distribution. Here, we present MaveDB ( https://www.mavedb.org ), a public repository for large-scale measurements of sequence variant impact, designed for interoperability with applications to interpret these datasets. We also describe the first such application, MaveVis, which retrieves, visualizes, and contextualizes variant effect maps. Together, the database and applications will empower the community to mine these powerful datasets.
Mutagenesis is a widely used method for identifying protein positions that are important for function or ligand binding. Advances in high-throughput DNA sequencing and mutagenesis techniques have ...enabled measurement of the effects of nearly all possible amino acid substitutions in many proteins. The resulting large-scale mutagenesis data sets offer a unique opportunity to draw general conclusions about the effects of different amino acid substitutions. Thus, we analyzed 34,373 mutations in 14 proteins whose effects were measured using large-scale mutagenesis approaches. Methionine was the most tolerated substitution, while proline was the least tolerated. We found that several substitutions, including histidine and asparagine, best recapitulated the effects of other substitutions, even when the identity of the wild-type amino acid was considered. The effects of histidine and asparagine substitutions also correlated best with the effects of other substitutions in different structural contexts. Furthermore, highly disruptive substitutions like aspartic and glutamic acid had the most discriminatory power for detecting ligand interface positions. Our work highlights the utility of large-scale mutagenesis data, and our conclusions can help guide future single substitution mutational scans.
•Presents experimental method for heat generation measurement in Li-ion battery.•Method is based on temperature and heat flux measurement.•Experimental data agrees with well-established theoretical ...models.•Results may contribute towards thermal safety of Li-ion cells.
Understanding the rate of heat generation in a lithium-ion cell is critical for its safety and performance behavior. This paper presents in situ measurements of the heat generation rate for a prismatic Lithium-ion battery at 1C, 2C, 3C and 4C discharge rates and 5°C, 15°C, 25°C, and 35°C boundary conditions (BCs). For this work, an aluminum-laminated battery consisting of LiFePO4 cathode material with 20Ah capacity was adopted to investigate the variation of the rate of heat generation as a function of the discharge capacity. Ten thermocouples and three heat flux sensors were applied to the battery surface at distributed locations. The results of this study show that the highest rate of heat generation was found to be 91W for 4C discharge rate and 5°C BC while the minimum value was 13W measured at 1C discharge rate and 35°C BC. It was also found that the increase in discharge rate and thus the discharge current caused consistent increase in the heat generation rate for equal depth of discharge points. A model is later developed using the neural network approach and validated. The heat generation rate predicted by the model demonstrates an identical behavior with experimental results.
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