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This work models a last-mile network design problem for an e-retailer with a capacitated two-echelon distribution structure - typical in e-retail last-mile distribution, catering to a market with a stochastic and dynamic daily customer demand requesting delivery within time-windows. Considering the distribution evnironment, this work formulates last-mile network design problem for this e-retailer as a dynamic-stochastic two capacitated location routing problem with time-windows. In doing so, this work splits the last-mile network design problem into its constituent strategic, tactical, and operational decisions. Here, the strategic decisions undertake long-term planning to develop a distribution structure with appropriate distribution facilities and a suitable delivery fleet to service the expected customer demand in the planning horizon. The tactical decisions pertain to medium-term day-to-day planning of last-mile delivery operations to establish efficient goods flow in this distribution structure to service the daily stochastic customer demand. And finally, operational decisions involve immediate short-term planning to fine-tune this last-mile delivery to service the requests arriving dynamically through the day. Note, the last-mile network design problem formulated as a location routing problem constitutes three subproblems encompassing facility location problem, customer allocation problem, and vehicle routing problem, each of which are NP-hard combinatorial optimization problems. To this end, this work develops an adaptive large neighborhood search meta-heuristic algorithm that searches through the neighborhood by destroying and consequently repairing the solution thereby reconfiguring large portions of the solution with specific operators that are chosen adaptively in each iteration of the algorithm, hence the name adaptive large neighborhood search. Further, considering the stochastic and dynamic nature of the delivery environment, this work develops a Monte-Carlo framework simulating each day in the planning horizon, with each day divided into 1-hr timeslots, and with each time-slot accepting customer requests for service by the end of the day. In particular, the framework assumes the e-retailer will delay route commitments until the last-feasible time-slot to accumulate customer requests and consequently assign them to an uncommitted delivery route. Note, a delivery route is committed once the e-retailer starts loading packages assigned to this delivery route onto the delivery vehicle assigned for this delivery route. At the end of every time-slot then, this framework assumes the e-retailer integrates the new customer requests by inserting these customer nodes into such uncommitted delivery routes in a manner that results in the least increase in distribution cost keeping the customer-distribution facility allocation fixed. Thus, the framework iterates through the time-slots with the e-retailer processing route commitments, accumulating customer requests, and subsequently integrating them into the delivery operations for the day. E-commerce has the potential to make urban goods flow economically viable, environmentally efficient, and socially equitable. However, as e-retailers compete with increasingly consumer-focused services, urban freight witnesses a significant increase in associated distribution costs and negative externalities particularly affecting those living close to logistics clusters. Hence, to remain competitive, e-retailers deploy alternate last-mile distribution strategies. These alternate strategies, such as those that include use of electric delivery trucks for last-mile operations, a fleet of crowdsourced drivers for last-mile delivery, consolidation facilities coupled with light-duty delivery vehicles for a multi-echelon distribution, or collection points for customer pickup, can restore sustainable urban goods flow. Thus, in this study, the authors investigate the opportunities and challenges associated with such alternate last-mile distribution strategies for an e-retailer offering expedited service with rush delivery within strict timeframes. To this end, the authors formulate a last-mile network design (LMND) problem as a dynamic-stochastic two-echelon capacitated location routing problem with time-windows (DS-2E-C-LRP-TW) addressed with an adaptive large neighborhood search (ALNS) metaheuristic.

Project: Coupled Model Intercomparison Project Phase 6 (CMIP6) datasets - These data have been generated as part of the internationally-coordinated Coupled Model Intercomparison Project Phase 6 (CMIP6; see also GMD Special Issue: http://www.geosci-model-dev.net/special_issue590.html). The simulation data provides a basis for climate research designed to answer fundamental science questions and serves as resource for authors of the Sixth Assessment Report of the Intergovernmental Panel on Climate Change (IPCC-AR6). CMIP6 is a project coordinated by the Working Group on Coupled Modelling (WGCM) as part of the World Climate Research Programme (WCRP). Phase 6 builds on previous phases executed under the leadership of the Program for Climate Model Diagnosis and Intercomparison (PCMDI) and relies on the Earth System Grid Federation (ESGF) and the Centre for Environmental Data Analysis (CEDA) along with numerous related activities for implementation. The original data is hosted and partially replicated on a federated collection of data nodes, and most of the data relied on by the IPCC is being archived for long-term preservation at the IPCC Data Distribution Centre (IPCC DDC) hosted by the German Climate Computing Center (DKRZ). The project includes simulations from about 120 global climate models and around 45 institutions and organizations worldwide. Summary: These data include the subset used by IPCC AR6 WGI authors of the datasets originally published in ESGF for 'CMIP6.ScenarioMIP.NOAA-GFDL.GFDL-ESM4.ssp245' with the full Data Reference Syntax following the template 'mip_era.activity_id.institution_id.source_id.experiment_id.member_id.table_id.variable_id.grid_label.version'. The GFDL-ESM4 climate model, released in 2018, includes the following components: aerosol: interactive, atmos: GFDL-AM4.1 (Cubed-sphere (c96) - 1 degree nominal horizontal resolution; 360 x 180 longitude/latitude; 49 levels; top level 1 Pa), atmosChem: GFDL-ATMCHEM4.1 (full atmospheric chemistry), land: GFDL-LM4.1, landIce: GFDL-LM4.1, ocean: GFDL-OM4p5 (GFDL-MOM6, tripolar - nominal 0.5 deg; 720 x 576 longitude/latitude; 75 levels; top grid cell 0-2 m), ocnBgchem: GFDL-COBALTv2, seaIce: GFDL-SIM4p5 (GFDL-SIS2.0, tripolar - nominal 0.5 deg; 720 x 576 longitude/latitude; 5 layers; 5 thickness categories). The model was run by the National Oceanic and Atmospheric Administration, Geophysical Fluid Dynamics Laboratory, Princeton, NJ 08540, USA (NOAA-GFDL) in native nominal resolutions: aerosol: 100 km, atmos: 100 km, atmosChem: 100 km, land: 100 km, landIce: 100 km, ocean: 50 km, ocnBgchem: 50 km, seaIce: 50 km.

The purpose of this study is to evaluate the safety and tolerability of the JAK2 inhibitor XL019 administered orally in adults with Polycythemia Vera.

For this manuscript, there were three types of methods performed to make our main conclusions: genetic diversity and structure analyses, downloading and mapping butternut fossil pollen during the last 20,000 years, and modeling and hindcasting butternut's (Juglans cinerea) distribution 20,000 years ago to present. Genetic analyses and species distribution modeling were performed in Emily Schumacher’s Github repository (https://github.com/ekschumacher/butternut) and pollen analyses and mapping were performed in Alissa Brown’s repository (https://github.com/alissab/juglans). Here is information detailing the Genetic data Data collection description: To perform genetic diversity and structure analyses on butternut, we used genetic data from the publication Hoban et al. (2010) and genetic data from newer sampling efforts on butternut from 2011 - 2015. Individuals were collected by Jeanne Romero-Severson, Sean Hoban, and Martin Williams over the course of ~ten years with a major sampling effort closer to 2009 followed up by another round of sampling 2012 - 2015. The initial 1,004 butternut individuals that were collected were genotyped by Sean Hoban and then the subsequent 757 individuals were genotyped in the Romero-Severson lab at Notre Dame non-consecutively. Genotyping was performed according to Hoban et al. (2008); DNA was extracted from fresh cut twigs using DNeasy Plant Mini kits (QIAGEN). PCR was performed by using 1.5 mM MgCl2, 1x PCR buffer [50 mm KCl, 10 mm Tris-HCl (pH 9.0), 0.1% Triton-X-100 (Fisher BioTech)], 0.2 mm dNTPs, 4 pm each forward and reverse primer, 4% Bovine Serum Albumin, 0.25 U TaKaRa Ex Taq Polymerase (Panvera), and 20 ng DNA template (10 μL total volume). The PCR temperature profile was as follows: 2 min at 94 °C; 30 cycles of 94 °C for 30 s, Ta for 30 s, and 72 °C for 30 s; 45 min at 60 °C; and 10 min at 72 °C on a PTC-225 Peltier Thermal Cycler (MJ Research). The process of assessing loci and rebinning for differences in years is detailed in the Schumacher et al. (2022) manuscript. Data files butternut_44pop.gen: Genepop file of original 1,761 butternut individuals, sampling described above, separated into original 44 sampling populations. butternut_24pop_nomd.gen: Genepop file of 1,635 butternut individuals, following rebinning based on researcher binning, reduced based on geographic isolation and missing data, organized into 24 populations. Used to generate all genetic diversity results. butternut_24pop_relate_red.gen: Genepop file of 993 butternut individuals, reduced for 25% relatedness, used to generate all clustering analyses. butternut_26pop_nomd.gen: Genepop file of 1,662 butternut individuals, reduced based on geographic isolation and missing data, including Quebec individuals, organized into 26 populations. Used to generate genetic diversity results with Quebec individuals. butternut_26pop_relate_red.gen: Genepop file of 1,015 butternut individuals, including Quebec individuals, reduced for 25% relatedness, used to generate clustering analyses with Quebec individuals. Fossil Pollen Data collection description: Pollen records for butternut were downloaded from Neotoma Paleoecology Database in 500-year time increments and visualized in 1,000 year-time increments 20,000 years ago to present. Data files butternut_pollen_data.csv: CSV of pollen records used for analyses and mapping. Includes original coordinates for each record (“og_long”, “og_lat”), the count of Juglans cinerea pollen at each site (“Juglans_cinerea_count”), and the age of the record (“Age”). To create the final maps, the coordinates were projected into Albers for each record (“Proj_Long,” “Proj_Lat”). Species Distribution Modeling and Hindcast Modeling Data collection description: We wanted to identify butternut's ecological preferences using boosted regression trees (BRT) and then hindcast distribution models into the past to identify migration pathways and locations of glacial refugia. Species distribution modeling was performed using boosted regression trees according to Elith et al. (2008). To run BRT, we needed to: 1. Reduce occurrence records to account for spatial autocorrelation, 2. Generate pseudo-absence points to identify the habitat where butternut is not found, 3. Obtain and extract the 19 bioclimatic variables at all points, 4. Select ecological variables least correlated with each other and most correlated with butternut presence. The BRT model that predicted butternut's ecological niche was then used to hypothesize butternut's suitable habitat and range shifts in the past. We downloaded occurrence records according to Beckman et al. (2019) as described here: https://github.com/MortonArb-ForestEcology/IMLS_CollectionsValue. The habitat suitability map generated from the BRT were projected into the past 20,000 years using Paleoclim variables (Brown et al., 2018). Data files butternut_BRT_var.csv: A CSV of the butternut presence and pseudoabsence points and extracted Bioclim variables (Fick & Hijman, 2017) used to run BRT in the final manuscript. Longitude and latitude coordinates are projected into Albers Equal Area Conic project, same with all of the ecological variables. Presence points are indicated with a 1 in the “PA” column and pseudo-absence points are indicated with a “0.” The variables most correlated with presence and least correlated with each other in this analysis were precipitation of the wettest month (“PwetM”), mean diurnal range (“MDR”), mean temperature of the driest quarter (“MTDQ”), mean temperature of the wettest quarter (“MTwetQ”), and seasonal precipitation (“precip_season”). References Brown, J. L., Hill, D. J., Dolan, A. M., Carnaval, A. C., & Haywood, A. M. (2018). PaleoClim, high spatial resolution paleoclimate surfaces for global land areas. Scientific Data, 5, 1-9 Elith, J., Leathwick, J. R., & Hastie, T. (2008). A working guide to boosted regression trees. Journal of Animal Ecology, 77, 802-813. Fick, S. E., & Hijmans, R. J. (2017). WorldClim 2: new 1‐km spatial resolution climate surfaces for global land areas. International Journal of Climatology, 37, 4302-4315. Hoban, S., Anderson, R., McCleary, T., Schlarbaum, S., and Romero-Severson, J. (2008). Thirteen nuclear microsatellite loci for butternut (Juglans cinerea L.). Molecular Ecology Resources, 8, 643-646. Hoban, S. M., Borkowski, D. S., Brosi, S. L., McCleary, T. S., Thompson, L. M., McLachlan, J. S., ... Romero-Severson, J. (2010). Range‐wide distribution of genetic diversity in the North American tree Juglans cinerea: A product of range shifts, not ecological marginality or recent population decline. Molecular Ecology, 19, 4876-4891. Aim: Range shifts are a key process that determine species distributions and genetic patterns. A previous investigation reported that Juglans cinerea (butternut) has lower genetic diversity at higher latitudes, hypothesized to be the result of range shifts following the last glacial period. However, genetic patterns can also be impacted by modern ecogeographic conditions. Therefore, we re-investigate genetic patterns of butternut with additional northern population sampling, hindcasted species distribution models, and fossil pollen records to clarify the impact of glaciation on butternut. Location: Eastern North America Taxon: Juglans cinerea (L., Juglandaceae) (butternut) Methods: Using 11 microsatellites, we examined range-wide spatial patterns of genetic diversity metrics (allelic richness, heterozygosity, FST) for previously studied butternut individuals and an additional 757 samples. We constructed hindcast species distribution models and mapped fossil pollen records to evaluate habitat suitability and evidence of species’ presence throughout space and time. Results: Contrary to previous work on butternut, we found that genetic diversity increased with distance to range edge, and previous latitudinal clines in diversity were likely due to a few outlier populations. Populations in New Brunswick, Canada were genetically distinct from other populations. At the Last Glacial Maximum, pollen records demonstrate butternut likely persisted near the glacial margin, and hindcast species distribution models identified suitable habitat in the southern United States and near Nova Scotia. Main conclusions: Genetic patterns in butternut may be shaped by both glaciation and modern environmental conditions. Pollen records and hindcast species distribution models combined with genetic distinctiveness in New Brunswick suggest that butternut may have persisted in cryptic northern refugia. We suggest that thorough sampling across a species range and evaluating multiple lines of evidence are essential to understanding past species movements. Data was cleaned and processed in R - genetic data cleaning and analyses and species distribution modeling methods were performed in Emily Schumacher's butternut repository and fossil pollen data cleaning and modeling was performed in Alissa Brown's juglans repository. Steps for performing data cleanining, analyses, and generating figures for the manuscript are described within each repo.

A lack of adequate high resolution climate proxy records for the Last Glacial Maximum (LGM) has prevented the extrapolation of climate–solar linkages on centennial time scales prior of the Holocene. Therefore, it is still unknown whether centennial climate variations of the last ten thousand years convey a universal climate change or merely represent a characteristic of the Holocene. Recently published high resolution climate proxy records for the LGM allowed us to extrapolate climate–solar linkages on centennial time scales ahead of the Holocene. Here we present the analysis of a high resolution pollen concentration record from Lake Kotokel in southern Siberia, Russia, during the LGM. The record reflects the dynamics of vegetation zones and temperature change with a resolution of ~ 40 years in the continental climate of north-eastern Asia. We demonstrate that our pollen concentration record, the oxygen isotope δ18O record from the Greenland ice core project NGRIP (NorthGRIP), the dust-fall contributions in Lake Qinghai, China, grain size in the Gulang and Jingyuan loess deposits, China, and the composite oxygen isotope δ18O record from the Alpine cave system 7H reveal cooler to warmer climate fluctuations between ~ 20.6 and 26 ka. Such fluctuations correspond to the ~ 1000-yr, 500-600-yr and 210-250-yr cycles possibly linked to the solar activity variations and recognized in high resolution Holocene proxies all over the world. We further show that climate fluctuations in the LGM and Holocene are spectrally similar suggesting that linkages between climate proxies and solar activity at the centennial time scale in the Holocene can be extended to the LGM. {"references": ["Vadim A. Kravchinsky, Rui Zhang, Ryan Borowiecki, Pavel E. Tarasov, Mirko van der Baan, Taslima Anwar, Avto Goguitchaichvili, Stefanie M\u00fcller, 2021. Centennial scale climate oscillations from southern Siberia in the Last Glacial Maximum. Quaternary Science Reviews, in press."]}

Physical and biogeochemical variables from the NOAA-GFDL Earth System Model 2M experiments, and previously published observation-based datasets, used for the study 'Hydrological cycle amplification reshapes warming-driven oxygen loss in Atlantic Ocean'.

Project: Coupled Model Intercomparison Project Phase 6 (CMIP6) datasets - These data have been generated as part of the internationally-coordinated Coupled Model Intercomparison Project Phase 6 (CMIP6; see also GMD Special Issue: http://www.geosci-model-dev.net/special_issue590.html). The simulation data provides a basis for climate research designed to answer fundamental science questions and serves as resource for authors of the Sixth Assessment Report of the Intergovernmental Panel on Climate Change (IPCC-AR6). CMIP6 is a project coordinated by the Working Group on Coupled Modelling (WGCM) as part of the World Climate Research Programme (WCRP). Phase 6 builds on previous phases executed under the leadership of the Program for Climate Model Diagnosis and Intercomparison (PCMDI) and relies on the Earth System Grid Federation (ESGF) and the Centre for Environmental Data Analysis (CEDA) along with numerous related activities for implementation. The original data is hosted and partially replicated on a federated collection of data nodes, and most of the data relied on by the IPCC is being archived for long-term preservation at the IPCC Data Distribution Centre (IPCC DDC) hosted by the German Climate Computing Center (DKRZ). The project includes simulations from about 120 global climate models and around 45 institutions and organizations worldwide. Summary: These data include the subset used by IPCC AR6 WGI authors of the datasets originally published in ESGF for 'CMIP6.ScenarioMIP.CAMS.CAMS-CSM1-0.ssp119' with the full Data Reference Syntax following the template 'mip_era.activity_id.institution_id.source_id.experiment_id.member_id.table_id.variable_id.grid_label.version'. The CAMS-CSM 1.0 climate model, released in 2016, includes the following components: atmos: ECHAM5_CAMS (T106; 320 x 160 longitude/latitude; 31 levels; top level 10 mb), land: CoLM 1.0, ocean: MOM4 (tripolar; 360 x 200 longitude/latitude, primarily 1deg latitude/longitude, down to 1/3deg within 30deg of the equatorial tropics; 50 levels; top grid cell 0-10 m), seaIce: SIS 1.0. The model was run by the Chinese Academy of Meteorological Sciences, Beijing 100081, China (CAMS) in native nominal resolutions: atmos: 100 km, land: 100 km, ocean: 100 km, seaIce: 100 km.

As part of global efforts to reduce dependence on carbon-based energy sources there has been a rapid increase in the installation of renewable energy devices. The installation and operation of these devices can result in conflicts with wildlife. In the marine environment, mammals may avoid wind farms that are under construction or operating. Such avoidance may lead to more time spent travelling or displacement from key habitats. A paucity of data on at-sea movements of marine mammals around wind farms limits our understanding of the nature of their potential impacts. Here, we present the results of a telemetry study on harbour seals Phoca vitulina in The Wash, south-east England, an area where wind farms are being constructed using impact pile driving. We investigated whether seals avoid wind farms during operation, construction in its entirety, or during piling activity. The study was carried out using historical telemetry data collected prior to any wind farm development and telemetry data collected in 2012 during the construction of one wind farm and the operation of another. Within an operational wind farm, there was a close-to-significant increase in seal usage compared to prior to wind farm development. However, the wind farm was at the edge of a large area of increased usage, so the presence of the wind farm was unlikely to be the cause. There was no significant displacement during construction as a whole. However, during piling, seal usage (abundance) was significantly reduced up to 25 km from the piling activity; within 25 km of the centre of the wind farm, there was a 19 to 83% (95% confidence intervals) decrease in usage compared to during breaks in piling, equating to a mean estimated displacement of 440 individuals. This amounts to significant displacement starting from predicted received levels of between 166 and 178 dB re 1 μPa(p-p). Displacement was limited to piling activity; within 2 h of cessation of pile driving, seals were distributed as per the non-piling scenario. Synthesis and applications. Our spatial and temporal quantification of avoidance of wind farms by harbour seals is critical to reduce uncertainty and increase robustness in environmental impact assessments of future developments. Specifically, the results will allow policymakers to produce industry guidance on the likelihood of displacement of seals in response to pile driving; the relationship between sound levels and avoidance rates; and the duration of any avoidance, thus allowing far more accurate environmental assessments to be carried out during the consenting process. Further, our results can be used to inform mitigation strategies in terms of both the sound levels likely to cause displacement and what temporal patterns of piling would minimize the magnitude of the energetic impacts of displacement. Wash_diagWash_diag.xlsx is the historic location data (pre windfarm construction) for the 19 individuals used in the analysis described in Russell et al.

Here, we investigate how stochasticity and age-dependence in energy dynamics influence maternal allocation in iteroparous females. We develop a state-dependent model to calculate the optimal maternal allocation strategy with respect to maternal age and energy reserves, focusing on allocation in a single offspring at a time. We introduce stochasticity in energetic costs– in terms of the amount of energy required to forage successfully and individual differences in metabolism – and in feeding success. We systematically assess how allocation is influenced by age-dependence in energetic costs, feeding success, energy intake per successful feeding attempt, and environmentally-driven mortality. First, using stochastic dynamic programming, we calculate the optimal amount of reserves M that mothers allocate to each offspring depending on their own reserves R and age A. The optimal life history strategy is then the set of allocation decisions M(R, A) over the whole lifespan which maximizes the total reproductive success of distant descendants. Second, we simulated the life histories of 1000 mothers following the optimisation strategy and the reserves at the start of adulthood R1, the distribution of which was determined, the distribution of which was determined using an iterative procedure as described . For each individual, we calculated maternal allocation Mt, maternal reserves Rt, and relative allocation Mt⁄Rt at each time period t. The relative allocation helps us to understand how resources are partitioned between mother and offspring. Third, we consider how the optimal strategy varies when there is age-dependence in resource acquisition, energetic costs and survival. Specifically, we include varying scenarios with an age-dependent increase or a decrease with age in energetic costs (c_t), feeding success (q_t), energy intake per successful feeding attempt (y_t), and environmentally-driven extrinsic mortality rate (d_t) (Table 2). We consider the age-dependence of parameters one at a time or in pairs, altering the slope, intercept, or asymptote of the age-dependence (linear or asymptotic function). Our aim is to identify whether the observed reproductive senescence can arise from optimal maternal allocation. As such, we do not impose a decline in selection in later life as all offspring are equally valuable at all ages (for a given maternal allocation), and there are no mutations. For each scenario, we run the backward iteration process with these age-dependent functions, obtain the allocation strategy, and simulate the life history of 1000 individuals based on the novel strategy. We then fit quadratic and linear models to the reproduction of these 1000 individuals using the lme function, nlme package in R. For these models, the response variable is the maternal allocation Mt and explanatory variables are the time period t and t2 (for the quadratic fit only), with individual identity as a random term. We use likelihood ratio tests to compare linear and quadratic models using the anova function (package nlme) with the maximum-likelihood method. If the comparison is significant (p-value <0.05), we considered the quadratic model to have a better fit, otherwise the linear model is considered more parsimonious. We were particularly interested in identifying scenarios where the fit was quadratic with a negative quadratic term. For each scenario, the pseudo R2 conditional value (proportion of variance explained by the fixed and random terms, accounting for individual identity) is calculated to assess the goodness-of-fit of the lme model, on a scale from 0 to 1, using the “r.squared” function, package gabtool. All calculations and coding are done in R. Iteroparous parents face a trade-off between allocating current resources to reproduction versus maximizing survival to produce further offspring. Optimal allocation varies across age, and follows a hump-shaped pattern across diverse taxa, including mammals, birds and invertebrates. This non-linear allocation pattern lacks a general theoretical explanation, potentially because most studies focus on offspring number rather than quality and do not incorporate uncertainty or age-dependence in energy intake or costs. Here, we develop a life history model of maternal allocation in iteroparous animals. We identify the optimal allocation strategy in response to stochasticity when energetic costs, feeding success, energy intake, and environmentally-driven mortality risk are age-dependent. As a case study, we use tsetse, a viviparous insect that produces one offspring per reproductive attempt and relies on an uncertain food supply of vertebrate blood. Diverse scenarios generate a hump-shaped allocation: when energetic costs and energy intake increase with age; and also when energy intake decreases, and energetic costs increase or decrease. Feeding success and mortality risk have little influence on age-dependence in allocation. We conclude that ubiquitous evidence for age-dependence in these influential traits can explain the prevalence of non-linear maternal allocation across diverse taxonomic groups.