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The ε4-allele variant of apolipoprotein E (ApoE4) is the strongest genetic risk factor for Alzheimer’s disease, although it only differs from its neutral counterpart ApoE3 by a single amino acid substitution. While ApoE4 influences the formation of plaques and neurofibrillary tangles, the structural determinants of pathogenicity remain undetermined due to limited structural information. Previous studies have led to conflicting models of the C-terminal region positioning with respect to the N-terminal domain across isoforms largely because the data are potentially confounded by the presence of heterogeneous oligomers. Here, we apply a combination of single-molecule spectroscopy and molecular dynamics simulations to construct an atomically detailed model of monomeric ApoE4 and probe the effect of lipid association. Importantly, our approach overcomes previous limitations by allowing us to work at picomolar concentrations where only the monomer is present. Our data reveal that ApoE4 is far more disordered and extended than previously thought and retains significant conformational heterogeneity after binding lipids. Comparing the proximity of the N- and C-terminal domains across the three major isoforms (ApoE4, ApoE3, and ApoE2) suggests that all maintain heterogeneous conformations in their monomeric form, with ApoE2 adopting a slightly more compact ensemble. Overall, these data provide a foundation for understanding how ApoE4 differs from nonpathogenic and protective variants of the protein.

Self-assembly of nanoparticles leading to the formation of colloidal clusters often serves as the representative analogue for understanding molecular assembly. Unravelling the in situ structure and dynamics of such clusters in liquid suspensions is highly challenging. Presently colloidal clusters are first isolated from their generating environment and then their structures are probed by light scattering methods. In order to measure the in situ structure and dynamics of colloidal clusters, we have generated them using the high-repetition-rate femtosecond laser pulse optical tweezer. Since the constituent of our dimer, trimer or tetramer clusters are 250 nm radius two-photon resonant fluorophore coated nanospheres under the optical trap, they inherently produce Two-Photon Fluorescence, which undergo intra-nanosphere Fluorescence Energy Transfer. This unique energy transfer signature, in turn, enables us to visualize structures and orientations of these colloidal clusters during the process of their formation and subsequent dynamics in a liquid suspension. We also show that due to shape-birefringence, orientation and structural control of these colloidal clusters are possible as the polarization of the trapping laser is changed from linear to circular. We thus report important progress in sampling the smallest possible aggregates of nanoparticles, dimers, trimers or tetramers, formed early in the self-assembly process.

Robotic handling systems are increasingly applied in distribution centers. They require little space, provide flexibility in managing varying demand requirements, and are able to work 24/7. This makes them particularly fit for e-commerce operations. This paper reviews new categories of automated and robotic handling systems, such as shuttle-based storage and retrieval systems, shuttle-based compact storage systems, and robotic mobile fulfillment systems. For each system, we categorize the literature in three groups: system analysis, design optimization, and operations planning and control. Our focus is to identify the research issue and operations research modeling methodology adopted to analyze the problem. We find that many new robotic systems and applications have hardly been studied in academic literature, despite their increasing use in practice. Because of unique system features (such as autonomous control, flexible layout, networked and dynamic operation), new models and methods are needed to address the design and operational control challenges for such systems, in particular, for the integration of subsystems. Integrated robotic warehouse systems will form the next category of warehouses. All vital warehouse design, planning, and control logic, such as methods to design layout, storage and order-picking system selection, storage slotting, order batching, picker routing, and picker to order assignment, will have to be revisited for new robotized warehouses.

Bulk-service multi-server queues with heterogeneous server capacity and thresholds are commonly seen in several situations such as passenger transport or package delivery services. In this paper, we develop a novel decomposition-based solution approach for such queues using arguments from renewal theory. We then obtain the distribution of the waiting time measure for multi-type server systems. We also obtain other useful performance measures such as utilization, expected throughput time, and expected queue lengths.

Predicting surface runoff and flooding in seasonally frozen areas such as the Red River of the North Basin (RRB) in USA is a challenging task. It depends on the knowledge of the complex process of infiltration in frozen soil, such as phase changes of water, ice content and distribution in the infiltration zone (the top 0–30 cm of the soil profile), soil pore size distribution, soil temperature and freeze–thaw cycles. In this study, the infiltration rates into frozen soil (Colvin silty clay loam according to the United States Department of Agriculture (USDA) Classification, and Chernozem according to Food and Agriculture Organization of the United Nations (FAO) international soil Classification) were measured at three different initial water contents: permanent wilting point (PWP), θpwp; field capacity (FC), θfc; and between FC and PWP, θmid. Laboratory infiltration experiments were conducted using a Cornell sprinkle infiltrometer with three replications for each initial water content. Volumetric soil water content (θv) and soil temperature at three depths were also continuously monitored using sensors. The average infiltration rates were 0.66, 0.38, and 0.59 cm/min for three initial water contents (θpwp, θmid, and θfc, respectively). Initial infiltration into frozen soil occurred quickly in the soil with θpwp because the soil was dry. Melted ice water contributed to the total soil water content over time, so it made the initial infiltration comparatively slower in the soil with θmid. Initial infiltration was also slower in the soil with θfc because the wet soil had very small pore space, so the soil rapidly reached its saturation after the infiltration started. The Horton infiltration equation was fitted with the observed infiltration rates for the soils with three initial water contents, and the goodness of fit was evaluated by using the coefficient of determination (R2) and the root-mean-square error (RMSE). The final infiltration rates from the fitted Horton equations were 0.060, 0.010, and 0.027 cm/min for the initial water contents (θpwp, θmid, and θfc, respectively). The soil water content along the soil profile changed with the amount of infiltrating water over time. However, the initial soil water content and melt water from ice resulting from soil temperature rise regulated the change in soil water content. The amount of ice melt water contribution to soil water content change varied among the soils with different initial water contents (θpwp, θmid, and θfc, respectively). The θv changed gradually in the θpwp soil, rapidly at 0 °C in the θmid soil, and less in the θfc soil. The change in pore distribution due to freeze–thaw cycles and soil packing altered the soil hydraulic properties and the infiltration into the soil. This study can provide critical information for flood forecasting model and subsurface drainage design in the RRB.

BackgroundRainfall is the key contributor to provide soil moisture for wet season rice (T. Aman) cultivation. Erratic rainfall often causes water shortage resulting negative impact on plant growth and grain yield. The study aimed to determine suitable transplanting window that utilize maximum rainfall for T. Aman rice. Firstly, three years field experiment were conducted in Kushtia, Bangladesh from T. Aman, 2013 to 2015, and then the findings were implemented for another two adjacent locations, Panba and Rajshahi. The field experiment considered six transplanting dates of popular cultivar BR11 (growth duration 145 days) at 7 days interval starting from 10 July to 14 August. The CROPWAT 8.0 model was used to calculate crop water requirement (CWR), effective rainfall and irrigation demand (ID) from collected weather data in each growth phase of rice.ResultsIn all locations T. Aman rice received enormous rainfall up to vegetative phase resulting no irrigation demand in all three tested years. The early transplanting received more rainfall in reproductive phase than late planting. Thus, Irrigation demand increased at reproductive phase with delay transplanting in moderate drought prone Kushtia, Pabna and Rajshahi. A significant relationship (R2 = 0.71) observed between reproductive phase ID and grain yield, while grain yield responded weakly with the ID at ripening phase. Based on yield performance 10–24 July found suitable transplanting window for BR11 in Kushtia. Considering the relationship between ID and grain yield, 10–17 July and 10–24 July considered the best transplanting window in Pabna and Rajshahi, respectively.ConclusionsLocation specific suitable transplanting windows were selected considering minimum ID at reproductive phase and the maximum grain yield. Delay in transplanting demanded more irrigation and reduced grain yield. Whereas, early transplanting utilized maximum rainfall, reduced ID in reproductive stage and ensured desired grain yield.

In the changing climatic condition, temperature is the most vulnerable parameter and is projecting a trend of increase in the future. Crop growth and development process depend largely on air temperature. This study aims to determine the role of increasing air temperature in yield, crop water requirement (CWR), and other agronomic parameters of irrigated rice. Ceres-rice model associated in the Decision Support System for Agrotechnology Transfer (DSSAT) was used in 15 different locations of Bangladesh. Grain yield, growth duration, and crop water requirement of widely cultivated irrigated rice (Boro rice) variety BRRI dhan28 were analysed in normal temperature and elevated air temperature by 1°C, 2°C, 3°C, and 4°C. The result revealed detrimental effect of elevated temperature on growth duration and grain yield. The estimated highest growth duration reduction of 30 days was found in Moulvibazar for 4°C temperature rise. The grain yield reduction was projected by 0–17%, 16–35%, 31–49%, and 39–61% from the normal condition if the seasonal mean temperature increased by 1°C, 2°C, 3°C, and 4°C, respectively. The country average crop water requirement was found to be 405 mm of which the highest 445 mm and the lowest 358 mm were recorded in Moulvibazar and Chandpur, respectively. The study revealed that the country average rice CWR reduced by 5%, 8%, 12%, and 17% over the normal condition for 1°C, 2°C, 3°C, and 4°C rising temperature, respectively. For 1°C temperature rise, BRRI dhan28 life span shortened by 6.4 days, grain yield reduced by 695 kg, and estimated CWR decreased by 14 mm. The projected declining CWR indicated that irrigated rice will require less irrigation water, but it will cause considerable yield loss under elevated temperature. Though elevated temperature will save huge irrigation water used in country-wide Boro rice cultivation, the crop developers need to introduce new heat-tolerant cultivar to minimize yield loss.

Water productivity improvement is getting the prime concern to sustain irrigated rice production in the water-scarce areas of Bangladesh under changing climate. Besides, profitable cropping pattern selection is one of the major indicators of commercial agriculture. The study was conducted at Mithapukur and Pirganj Upazilas of Rangpur district during 2018–2020 to evaluate the water saving and profitability of three crop cropping patterns over two crops pattern. The experiment involved two improved patterns, T. Aman-Mustard-Boro (CP1) and T. Aman-Potato-Boro (CP2), and one locally popular pattern, T. Aman-Fallow-Boro (CP3). Irrigation management involved supplemental irrigation for T. Aman rice, irrigation application after disappearing standing water for Boro rice, and two irrigations at critical stages of potato and mustard. Both CP1 and CP2 received higher rainfall than CP3 because the delayed transplanting of Boro rice captured more rainfall. The improved patterns of CP1 and CP2 saved 22–40% of irrigation water compared with CP3. Among the patterns, CP2 achieved the highest rice equivalent yield (REY) of 21.1–33.6 t·ha−1 due to excellent potato production. Similarly, CP2 provided the highest irrigation water productivity because of higher REY as well as less irrigation requirement. Both CP1 and CP2 patterns returned a higher gross margin than CP3. The findings indicated that the inclusion of potato and mustard in the T. Aman-Fallow-Boro cropping pattern saved irrigation water as well as increased production and economic benefit. Adoption of these water-efficient cropping patterns may reduce groundwater irrigation in the water-scarce areas of Bangladesh.

Shuttle-based compact systems are new automated multideep unit-load storage systems with lifts that can potentially achieve both low operational cost and large volume flexibility. In this paper, we develop novel queuing network models to estimate the performance of both single-tier and multitier shuttle-based compact systems. Each tier is modeled as a multiclass semi-open queuing network, whereas the vertical transfer is modeled using an open queue. For a multitier system, the models corresponding to tiers and vertical transfer are linked together using the first and second moment information of the queue departure processes. The models can handle both specialized and generic shuttles and both continuous and discrete lifts. The accuracy of the models is validated through both simulation and a real case. Errors are acceptable for conceptualizing initial designs. Numerical studies provide new design insights. Results show that the best way to minimize expected throughput time in single-tier systems is to have a depth/width ratio around 1.25. Moreover, specialized shuttles are recommended for multitier systems because the higher cost of generic shuttles is not balanced by savings in reduced throughput time and equipment needs.

Autonomous vehicle-based storage and retrieval systems are commonly used in many fulfillment centers (e.g., e-commerce warehouses), because they allow a high- and flexible-throughput capacity. In these systems, roaming robots transport loads between a storage location and a workstation. Two main variants exist: horizontal , where the robots only move horizontally and use lifts for vertical transport, and a new variant vertical , where the robots can also travel vertically in the rack. This paper builds a framework to analyze the performance of the vertical system and compare its throughput capacity with the horizontal system. We build closed queueing network models for this that, in turn, are used to optimize the design. The results show that the optimal height-to-width ratio of a vertical system is around one. Because a large number of system robots may lead to blocking and delays, we compare the effects of different robot blocking protocols on the system throughput: robot Recirculation and Wait-on-Spot. The Wait-on-Spot policy produces a higher system throughput when the number of robots in the system is small. However, for a large number of robots in the system, the Recirculation policy dominates the Wait-on-Spot policy. Finally, we compare the operational costs of the vertical and horizontal transport systems. For systems with one load/unload (L/U) point, the vertical system always produces a similar or higher system throughput with a lower operating cost compared with the horizontal system with a discrete lift. It also outperforms the horizontal system with a continuous lift in systems with two L/U points.