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Changes in gray whale ( Eschrichtius robustus ) phenology and distribution are related to observed and hypothesized prey availability, bottom water temperature, salinity, sea ice persistence, integrated water column and sediment chlorophyll a , and patterns of wind-driven biophysical forcing in the northern Bering and eastern Chukchi seas. This portion of the Pacific Arctic includes four Distributed Biological Observatory (DBO) sampling regions. In the Bering Strait area, passive acoustic data showed marked declines in gray whale calling activity coincident with unprecedented wintertime sea ice loss there in 2017–2019, although some whales were seen there during DBO cruises in those years. In the northern Bering Sea, sightings during DBO cruises show changes in gray whale distribution coincident with a shrinking field of infaunal amphipods, with a significant decrease in prey abundance (r = -0.314, p<0.05) observed in the DBO 2 region over the 2010–2019 period. In the eastern Chukchi Sea, sightings during broad scale aerial surveys show that gray whale distribution is associated with localized areas of high infaunal crustacean abundance. Although infaunal crustacean prey abundance was unchanged in DBO regions 3, 4 and 5, a mid-decade shift in gray whale distribution corresponded to both: (i) a localized increase in infaunal prey abundance in DBO regions 4 and 5, and (ii) a correlation of whale relative abundance with wind patterns that can influence epi-benthic and pelagic prey availability. Specifically, in the northeastern Chukchi Sea, increased sighting rates (whales/km) associated with an ~110 km (60 nm) offshore shift in distribution was positively correlated with large scale and local wind patterns conducive to increased availability of krill. In the southern Chukchi Sea, gray whale distribution clustered in all years near an amphipod-krill ‘hotspot’ associated with a 50-60m deep trough. We discuss potential impacts of observed and inferred prey shifts on gray whale nutrition in the context of an ongoing unusual gray whale mortality event. To conclude, we use the conceptual Arctic Marine Pulses (AMP) model to frame hypotheses that may guide future research on whales in the Pacific Arctic marine ecosystem.

Imagery and sighting data on bowhead whale (Balaena mysticetus) carcasses documented from 2009 to 2018 during aerial surveys in the eastern Chukchi and western Beaufort seas have provided evidence for killer whale (Orcinus orca) predation on bowhead whales of the Bering–Chukchi–Beaufort Seas stock. The Aerial Surveys of Arctic Marine Mammals (ASAMM) project provides information on distribution, behavior, and relative density of marine mammals. ASAMM surveys large areas of bowhead whale and killer whale summer and autumn habitat and offers consistent information on bowhead whale carcasses. Thirty-three bowhead whale carcasses were documented in July–October, from 2009 to 2018. Carcasses were distributed across the eastern Chukchi and western Beaufort seas from 141.6° W to 168.1° W and 68.9° N to 72.0° N. Carcass sighting rates (carcasses/1000 km) varied by month, year, and region. Statistical results suggest an alternating series of high and low annual carcass sighting rates. Eighteen bowhead whale carcasses having injuries consistent with probable killer whale predation were photo-documented: four each in 2016 and 2018, three each in 2013 and 2015, two in 2012, and one each in 2010 and 2017. Four carcasses, two in 2015 and one each in 2013 and 2018, were likely whales struck and lost during aboriginal subsistence hunting. Cause of death could not be determined for 11 carcasses. This study is the first systematic inquiry into non-harvest related mortality of bowhead whales in the U.S. Pacific Arctic and provides multi-year evidence for killer whale predation on bowhead whales in this portion of their range.

Cetacean occurrence in the Chukchi Sea is seasonal and primarily driven by annual sea ice retreat and prey occurrence in spring through fall. Humpback whales (Megaptera novaeangliae), fin whales (Balaenoptera physalus), and minke whales (Balaenoptera acutorostrata), although often found in polar waters elsewhere, are not common in the eastern Chukchi Sea, and here are referred to as “subArctic” species. Increasing numbers of these subArctic cetacean species were documented during aerial surveys in the eastern Chukchi Sea (67°–72°N, 157°–169°W) in July–October 2008–2016. The majority (78%) of these sightings occurred on the continental shelf in the south-central Chukchi Sea (67°–69°N, 166°–169°W) in August and September. During similar aerial surveys in 1982–1991, there was a complete lack of sightings of subArctic species. The disparity in sightings between the two time periods could be due to increased marine mammal survey effort in recent years during the months when subArctic cetacean species would be expected to occur, population recoveries from commercial whaling, climate change, or, most likely, a combination of all three.

Examining Eastern North Pacific gray whale (Eschrichtius robustus) carcasses and tracking mortality and morbidity are essential for assessing the health of this stock. In the eastern Chukchi Sea, the expansive coastline relative to few coastal communities makes monitoring for and physical examination of gray whale carcasses difficult. The Aerial Surveys of Arctic Marine Mammals (ASAMM) project offers an unparalleled dataset of gray whale carcasses, documented and photographed from July to October 2009–2019, providing a unique opportunity to investigate imaged gray whale carcasses for possible cause of death. Surveys covered expanses of gray whale and killer whale (Orcinus orca) summer and autumn habitat. ASAMM documented a total of 59 gray whale carcasses, distributed across the eastern Chukchi Sea (67.5° N–72.0° N, 155.5° W–169.0° W). Carcass sighting rates ([CPUE] carcasses per 1000-km of effort) varied by month and year. The highest numbers of carcasses were observed in 2012 (13) and 2019 (8). August had the highest number of gray whale carcass sightings (22) and the highest carcass sighting rate (0.231 CPUE). Images were obtained for 56 gray whale carcasses. The majority (41) of imaged gray whale carcasses had injuries consistent with probable killer whale predation, and were photo-documented every year except 2010 (when no carcasses were seen) and 2011. Eight carcasses were suspect killer whale predation, and cause of death could not be determined for seven carcasses. These results will be valuable for evaluating mortality, concurrent with rapid oceanographic changes, and increases in anthropogenic activities.

We delineated and scored Biologically Important Areas (BIAs) in the Arctic region. The Arctic region extends from the Bering Strait to the Chukchi Sea, Beaufort Sea, Amundsen Gulf, and Viscount Melville Sound. This NOAA-led effort uses structured elicitation principles to build upon the first version of NOAA BIAs (BIA I) for cetaceans. In addition to narratives, maps, and metadata tables, BIA II products incorporated a scoring and labeling system to improve their utility and interpretability. BIAs are compilations of the best available science and have no inherent regulatory authority. They have been used by NOAA, other federal agencies, and the public to support marine spatial planning and marine mammal impact assessments, and to inform the development of conservation measures for cetaceans. Supporting evidence for Arctic BIA II came from data derived from aerial-, land-, and vessel-based surveys; satellite telemetry; passive acoustic monitoring; Indigenous knowledge; photo-identification; aboriginal subsistence harvests, including catch and sighting locations and stomach contents; and prey studies. BIAs were identified for bowhead ( Balaena mysticetus ), gray ( Eschrichtius robustus ), humpback ( Megaptera novaeangliae ), fin ( Balaenoptera physalus ), and beluga ( Delphinapterus leucas ) whales. In total, 44 BIAs were delineated and scored for the Arctic, including 12 reproduction, 24 feeding, and 8 migration BIAs. BIAs were identified in all months except January-March. Fifteen candidate areas did not have sufficient information to delineate as BIAs and were added to a watch list for future consideration in the BIA process. Some BIAs were transboundary between the Arctic region and the Aleutian Islands-Bering Sea region. Several BIAs were transnational, extending into territorial waters of Russia (in the Chukchi Sea) and Canada (in the Beaufort Sea), and a few BIAs were delineated in international waters.

We delineated and scored Biologically Important Areas (BIAs) for cetaceans in the Aleutian Islands and Bering Sea region. BIAs represent areas and times in which cetaceans are known to concentrate for activities related to reproduction, feeding, and migration, and also the known ranges of small and resident populations. This effort, the second led by the National Oceanic and Atmospheric Administration (NOAA), uses structured elicitation principles to build upon the first version of NOAA’s BIAs (BIA I) for cetaceans. Supporting evidence for BIA II came from aerial-, land-, and vessel-based surveys; satellite-tagging data; passive acoustic monitoring; Indigenous knowledge; photo-identification data; whaling data, including stomach and fecal contents; prey studies; and genetics. In addition to narratives, maps, and metadata tables, the BIA II products incorporate a scoring and labeling system, which will improve their utility and interpretability. BIAs are compilations of the best available science and have no inherent regulatory authority. They have been used by NOAA, other federal agencies, and the public to support planning and marine mammal impact assessments, and to inform the development of conservation measures for cetaceans. In the Aleutian Islands and Bering Sea region, a total of 19 BIAs were identified, delineated, and scored for seven species, including bowhead, North Pacific right, gray, humpback, fin, and sperm whales, and belugas. These include one hierarchical BIA for belugas that consists of one localized “child” BIA within an overarching “parent” BIA. There were 15 feeding, 3 migratory, and 1 small and resident population BIAs; no reproductive BIAs were identified. In some instances, information existed about a species’ use of a particular area and time, but the information was insufficient to confidently delineate the candidate BIA; in those cases, the candidate BIA was added to a watch list. A total of 22 watch list areas were identified and delineated for 10 species, including all species mentioned above and minke whales, harbor porpoises, and Dall’s porpoises. There were 15 feeding, 4 migratory, 2 reproductive, and 1 small and resident population watch list areas. Some BIAs and watch list areas were transboundary between the Aleutian Islands and Bering Sea region and the Arctic region.

Aerial line transect surveys were conducted during 19 July – 20 August in each of the years 2012 – 17, with onshore–offshore transects covering a study area of approximately 110 000 km², from 140˚ W to 157˚ W longitude and from shore to 72˚ N latitude. These data were used to estimate abundance of the eastern Chukchi Sea (ECS) stock of beluga whales. The data were stratified based on bathymetry to reflect strong large-scale gradients in beluga density. A half-normal key function was used to model detection from a dataset of 999 sightings of 2465 belugas. The detection function was found to depend significantly on sky condition and ice coverage. For the years 2012 through 2017, respectively, the estimated numbers of ECS belugas in the study area during the study period were 7355 (CV = 0.17), 6813 (CV = 0.18), 16 598 (CV = 0.21), 6456 (CV = 0.21), 6965 (CV = 0.23) and 13 305 (CV = 0.27). There is no statistically significant trend. These estimates do not correct for belugas outside the study region. Indeed, diverse data indicate that belugas venture far outside the study region and their distribution varies interannually due to prey availability and other factors. Recently reviewed tagging data suggest that correcting for whales outside the study area would approximately double our abundance estimates. These results provide no indication that the stock has substantially declined during these six years due to the impact of subsistence hunting, industrial activity or climate change, although interannual variation and estimated CVs are both large, thereby potentially masking small-scale impacts. Des levés aériens de transects en ligne ont été effectués entre le 19 juillet et le 20 août des années 2012 à 2017, les transects côtiers et extracôtiers couvrant une aire d’étude d’environ 110 000 km², de 140˚ à 157˚ de longitude ouest, et de la côte jusqu’à 72˚ de latitude nord. Ces données ont été utilisées pour estimer l’abondance du stock de bélugas de l’est de la mer des Tchouktches (ECS). Les données ont été stratifiées en fonction de la bathymétrie afin de tenir compte des gradients prononcés à grande échelle en matière de densité de bélugas. Une fonction clé demi-normale a été employée pour modéliser la détection à partir d’un ensemble de données de 999 observations de 2 465 bélugas. Il s’est avéré que la fonction de détection dépendait énormément de l’état du ciel et de la couverture de glace. Pour les années 2012 à 2017, respectivement, les nombres estimés de bélugas de l’ECS dans l’aire et la période étudiées s’élevaient à 7 355 (CV = 0,17), 6 813 (CV = 0,18), 16 598 (CV = 0,21), 6 456 (CV = 0,21), 6 965 (CV = 0,23) et 13 305 (CV = 0,27). Il n’y a pas de tendance statistiquement significative. Ces estimations ne comprennent pas de corrections pour les bélugas à l’extérieur de l’aire étudiée. En effet, diverses données indiquent que les bélugas s’aventurent loin en dehors de l’aire étudiée et que leur distribution varie d’une année à l’autre en fonction de la disponibilité des proies et d’autres facteurs. Selon des données de marquage examinées récemment, une correction visant à tenir compte des baleines en dehors de l’aire étudiée aurait pour effet de doubler approximativement nos estimations d’abondance. Ces résultats ne fournissent aucune indication selon laquelle le stock de bélugas a diminué considérablement pendant ces six années en raison des incidences de la chasse de subsistance, de l’activité industrielle ou du changement climatique, bien que la variation interannuelle et les estimations de CV soient toutes deux considérables, ce qui risque de dissimuler les incidences à petite échelle.

We analyzed data from line-transect aerial surveys for marine mammals conducted in the western Beaufort Sea (shore to 72˚ N, 140˚ – 157˚ W) from July to October of 2009 – 16 to investigate the distribution, behaviors, sighting rates, and habitat use preferences of bowhead and beluga whales. The habitat use data allowed for direct comparison with data collected in the same area from 1982 to 1991. Both species are ice-adapted, migrating through leads in sea ice in spring, and are seasonal inhabitants of the western Beaufort Sea during summer and fall. From 2009 to 2016, bowhead whales were seen in all survey months, with the highest overall sighting rate (whales per km) in August. Bowhead sighting rates were highest in the whales' preferred habitats: outer shelf habitat (51 – 200 m depth) in July and inner shelf-shallow habitat (≤ 20 m depth) in August, September, and October. Beluga whales were also seen in all survey months, with highest overall sighting rate in July. Beluga whales were overwhelmingly associated with continental slope habitat (201 – 2000 m depth) in all months. Bowhead whale distribution and depth preferences in summer months of 2009 – 16 differed from those observed in 1982 – 91, when bowheads were not seen during limited survey effort in July and preferred outer continental shelf habitat in August. These differences indicate that bowhead whale preference for shallow shelf habitat now occurs earlier in summer than it used to. Beluga whale distribution and depth preference remained similar between 1982 – 91 and 2009 – 16, with strong preference for continental slope during both periods. Differences in sea ice cover habitat association for both species are likely due more to the relative lack of sea ice in recent years compared to the earlier period than to shifts in habitat preference. Habitat partitioning between bowhead and beluga whales in the western Beaufort Sea remained evident except in July, when both species used continental slope habitat. In July – October 2009 – 16, the distribution, sighting rates, and behavior of both bowheads and belugas in the western Beaufort showed considerable interannual variation, which underscores the importance of annual sampling to accurate records of the complex western Beaufort Sea ecosystem. Nous avons analysé les données découlant de levés aériens de transects linéaires pour mammifères marins, levés effectués dans l'ouest de la mer de Beaufort (de la rive jusqu'à 72˚ N, et de 140˚ jusqu'à 157˚ O) de juillet à octobre 2009 à 2016. Ces levés avaient pour but d'étudier la distribution, les comportements, les taux d'observation ainsi que les préférences d'utilisation de l'habitat des baleines boréales et des bélugas. Les données relatives à l'utilisation de l'habitat ont permis d'établir des comparaisons directes avec les données recueillies dans le même secteur de 1982 à 1991. Ces deux espèces sont adaptées à la glace, migrent par des chenaux formés dans la glace de mer au printemps et sont des habitants saisonniers de l'ouest de la mer de Beaufort pendant l'été et l'automne. Entre 2009 et 2016, des baleines boréales ont été aperçues pendant tous les mois visés par les levés, le taux d'observation général le plus élevé (nombre de baleines par km) ayant été enregistré au mois d'août. Les taux d'observation des baleines boréales étaient les plus élevés dans les habitats préférés de ces baleines, soit l'habitat de la plateforme externe (de 51 m à 200 m de profondeur) en juillet et l'habitat de la plateforme interne peu profonde (≤ 20 m de profondeur) en août, en septembre et en octobre. Des bélugas ont également été aperçus pendant tous les mois visés par les levés, le taux d'observation général le plus élevé ayant été enregistré en juillet. Les bélugas étaient massivement associés à l'habitat de la pente continentale (de 201 m à 2 000 m de profondeur) pendant tous les mois. La distribution et les préférences de profondeur des baleines boréales pendant les mois d'été 2009 à 2016 différaient de celles observées de 1982 à 1991, lorsque les baleines boréales n'ont pas été aperçues dans le cadre des quelques levés qui ont été effectués en juillet et préféraient leur habitat de la plateforme continentale externe en août. Ces différences indiquent que la préférence des baleines boréales pour l'habitat de la plateforme peu profonde se manifeste maintenant plus tôt l'été qu'auparavant. De 1982 à 1991 et de 2009 à 2016, la distribution des bélugas et leur préférence de profondeur sont restées semblables, avec une préférence marquée pour la pente continentale pendant les deux périodes. Pour les deux espèces, les différences sur le plan de l'association de la couverture de glace marine sont vraisemblablement davantage attribuables au manque relatif de glace de mer ces dernières années comparativement à la période précédente plutôt qu'à une variation de la préférence de l'habitat. Dans l'ouest de la mer de Beaufort, la séparation de l'habitat entre les baleines boréales et les bélugas demeurait évidente, sauf en juillet, quand les deux espèces utilisaient l'habitat de la pente continentale. De juillet à octobre 2009 à 2016, la distribution, les taux d'observation et le comportement des baleines boréales et des bélugas dans l'ouest de la mer de Beaufort ont affiché une variation considérable d'une année à l'autre, ce qui fait ressortir l'importance de faire des échantillonnages annuels afin d'obtenir des données précises au sujet de l'écosystème complexe de l'ouest de la mer de Beaufort.

Dimerization is essential for activity of human epidermal growth factor receptors (HER1/EGFR, HER2/ErbB2, HER3/ErbB3, and ErbB4) and mediates intracellular signaling events leading to cancer cell proliferation, survival, and resistance to therapy. HER2 is the preferred dimerization partner. Activation of HER signaling pathways may be blocked by inhibition of dimer formation using a monoclonal antibody (MAb) directed against the dimerization domain of HER2. The murine MAb 2C4 that specifically binds the HER2 dimerization domain was cloned as a chimeric antibody, humanized using a computer-generated model to guide framework substitutions, and variants were tested as Fabs. Pharmacokinetics and toxicology were evaluated in rodents and cynomolgus monkeys. Cloning the variable domains of MAb 2C4 into a vector containing human kappa and CH1 domains allowed construction of a mouse-human chimeric Fab. DNA sequencing of the chimeric clone permitted identification of CDR residues. The full-length IgG1 of variant F-10 was equivalent in binding to chimeric IgG1 and was designated pertuzumab (rhuMAb 2C4; Omnitarg). Pertuzumab pharmacokinetics was best described by a two-compartment model with a distribution phase of <1 day, terminal half-life of approximately 10 days, and volume of distribution of approximately 40 mL/kg that approximates serum volume. With the exception of diarrhea, pertuzumab was generally well tolerated in cynomolgus monkeys. Pertuzumab, a recombinant humanized IgG1 MAb, is the first of a new class of agents known as HER dimerization inhibitors. Inhibition of HER dimerization may be an effective anticancer strategy in tumors with either normal or elevated expression of HER2.

The southern Chukchi Sea is one of the most productive areas in the world ocean. Over the past decade, there have been dramatic changes in this region in sea ice cover and in Bering Strait inflow, and it is now in the path of transpolar shipping and destinational ship traffic, including vessels supporting Arctic offshore oil and gas development and tourism, all of which are anticipated to increase with decreasing seasonal sea ice cover. Little research on cetaceans has been conducted in the southern Chukchi Sea, and most information on the occurrence of subarctic species (humpback whaleMegaptera novaeangliae, fin whaleBalaenoptera physalus, minke whaleB. acutorostrata, and killer whaleOrcinus orca) comes from the ships' logs of commercial whalers in the mid to late twentieth century and from observers stationed along the Chukotka Peninsula. Information on cetacean seasonal occurrence east of the International Date Line (IDL) in US waters is particularly scarce. To address this information gap, we compiled visual sightings and acoustic detections of subarctic cetaceans in the southern Chukchi Sea during summer and early autumn from 2009 to 2012. Humpback whales were common on both sides of the IDL in August and September. Fin and minke whales were widely distributed east of the IDL from July to September, and killer whales were seen sporadically but were the most widely dispersed of the four species. Comparisons of our results with historical records indicate that the incidence of subarctic cetaceans may be increasing in the southern Chukchi Sea. An increase in occurrence may simply be a post-commercial whaling recovery of whale numbers and seasonal range by each species, or it may reflect responses to ongoing climate change. Understanding current stock identity, spatial and temporal distribution, habitat preference, relative abundance, and potential impacts of climate change on these species will require cetacean-focused research in this region of the Arctic.