Depositional Setting and Quaternary Stratigraphy of the Sheepscot Estuary, Maine: A Preliminary Report

The Sheepscot River estuary in west-central coastal Maine is a typical example of a long linear embayment sculpted by glacial ice flowing nearly parallel to bedrock strike. After initial déglaciation 13,500 yrs. BP it was covered by glaciomarine mud, the Presumpscot Formation. Isostatic rebound resulted in a rapid sea-level fall and the channeling, winnowing, and consolidation of the Presumpscot Formation, until sea-level reached a lowstand about 65 m below present, 9500 yrs. BP. Subsequent sea-level rise caused flooding of the paleovalley of the Sheepscot, with reworking of the Pleistocene. High resolution seismic reflection profiling, vibracoring, and surficial mapping has allowed reconstruction of the Quaternary stratigraphy and the generation of an evolutionary model of sedimentary environments. At present the estuary exhibits three zones : an outer zone stripped of sediment, a middle zone undergoing erosion by tidal currents and slumping on bluffs and channel margins, and an inner zone of sediment accumulation on flats and in marshes, with redistribution of sediments by tidal currents. This three-fold division held throughout the Holocene transgression, with sediments being temporarily stored in the upper regions of the estuary, and reworked as sea-level rise continued.L'estuaire de la rivière Sheepscot, au centre-ouest de la région côtière du Maine, est un bel exemple de baie allongée, sculptée par un glacier qui s'écoulait parallèlement à la direction du substratum rocheux. Après le début de la déglaciation, vers 13 500 BP, l'estuaire a été recouvert d'une boue glaciomarine, la Formation de Presumpscot. Le relèvement isostatique a eu pour conséquence la baisse rapide du niveau marin ainsi que la formation de chenaux, le triage des sédiments et la consolidation de la Formation de Presumpscot, jusqu'à 9500 BP, alors que le niveau marin était à 65 m sous le niveau actuel. La hausse subséquente du niveau marin a entraîné l'ennoiement de la paléo-vallée du Sheepscot, puis remaniement des sédiments au Pléistocène. Les sondages sismiques par réflexion, les vibro-carottages et la cartographie des formations superficielles ont permis de reconstituer la stratigraphie du Quaternaire et de créer un modèle de l'évolution des milieux de sédimentation. Actuellement, l'estuaire se divise en trois zones: une zone externe, décapée; une zone centrale en voie d'érosion par les courants de marée et affectée par des glissements dans les falaises et sur les bords des chenaux; une zone interne d'accumulation sur les hauts-fonds et dans les marais et de redistribution des sédiments par les courants de marée. Cette division zonale s'est maintenue tout au long de la transgression survenue à l'Holocène, avec accumulation des sédiments en amont de l'estuaire et remaniement au fur et à mesure de la hausse du niveau marin.Das Sheepscot-FlufJmùndungsbecken an der zentralen Westkùste von Maine ist ein Typisches Beispiel einer langen linearen Bucht, die durch glaziales EisflieBen fast parallel zur Fels-Streichrichtung geformt wurde. Nach dem Beginn der Enteisung 13,500 Jahre v.u.Z. war das Mùndungsbecken mit glazialmarinem Schlamm bedeckt, der Presumpscot Formation. Die isostatische Hebung fùhrte zu einem schnellen Sinken des Meeresniveaus und zur Bildung von Kanâlen, Sortierung und Konsolidierung der Presumpscot Formation, bis das Meeresniveau 9500 Jahre v.u.Z. einen Niedrigstand von ungefàhr 65 m unter dem heutigen Niveau erreichte. Das anschliepende Ansteigen des Meeresniveaus fùhrte zur Ùberschwemmung des Paleo-Tals von Sheepscot und zur Neuorganisation der Sedimente im Pleistozàn. Mittels seismischer Reflexionsprofile, Vibra-Karottage und Kartographie der Oberflâchen konnte die Stratigraphie des Quaternàrs rekonstruiert werden und ein Modell der Entwicklung der Sediment-Umgebungen geschaffen werden. Gegenwàrtig hat das Mùndungsbecken drei Zonen: eine àupere, von Sedimenten befreite Zone; eine mittlere Zone, die wegen der Gezeiten-Strômungen und der Erdrutsche an den Steilufern und den Ufern der Kanàle der Erosion ausgesetzt ist; eine innere Zone von Sediment-AbIagerungen in den Niederungen und Mârschen mit Neuverteilung der Sedimente durch die Gezeiten-Strômungen. Dièse dreiteilige Aufteilung hielt sich wàhrend der ganzen Transgression im Holozàn, mit Sedimenten, die zeitweise in den oberen Regionen der Mùndungsbucht abgelagert wurden und die, als das Steigen des Meeresniveaus weiterging, neu organisiert wurden

Phase II Study of the Efficacy and Safety of Pembrolizumab for Relapsed/Refractory Classic Hodgkin Lymphoma

Hodgkin, 9p24Purpose Hodgkin Reed-Sternberg cells harbor alterations in chromosome 9p24.1, leading to overexpression of programmed death-ligand 1 (PD-L1) and PD-L2. Pembrolizumab, a programmed death 1-blocking antibody, demonstrated a high overall response rate (ORR) in patients with relapsed or refractory classic Hodgkin lymphoma (rrHL) in phase I testing. Methods KEYNOTE-087 ( ClinicalTrials.gov identifier, NCT02453594) was a single-arm phase II study of pembrolizumab in three cohorts of patients with rrHL, defined on the basis of lymphoma progression after (1) autologous stem cell transplantation (ASCT) and subsequent brentuximab vedotin (BV); (2) salvage chemotherapy and BV, and thus, ineligible for ASCT because of chemoresistant disease; and (3) ASCT, but without BV after transplantation. Patients received pembrolizumab 200 mg once every 3 weeks. Response was assessed every 12 weeks. The primary end points were ORR by central review and safety. Results A total of 210 patients were enrolled and treated (69 in cohort 1, 81 in cohort 2, and 60 in cohort 3). At the time of analysis, patients received a median of 13 treatment cycles. Per central review, the ORR was 69.0% (95% CI, 62.3% to 75.2%), and the complete response rate was 22.4% (95% CI, 16.9% to 28.6%). By cohort, ORRs were 73.9% for cohort 1, 64.2% for cohort 2, and 70.0% for cohort 3. Thirty-one patients had a response 65 6 months. The safety profile was largely consistent with previous pembrolizumab studies. Conclusion Pembrolizumab was associated with high response rates and an acceptable safety profile in patients with rrHL, offering a new treatment paradigm for this disease

Methane Hydrates in Nature - Current Knowledge and Challenges

Recognizing the importance of methane hydrate research and the need for a coordinated effort, the United States Congress enacted the Methane Hydrate Research and Development Act of 2000. At the same time, the Ministry of International Trade and Industry in Japan launched a research program to develop plans for a methane hydrate exploratory drilling project in the Nankai Trough. India, China, the Republic of Korea, and other nations also have established large methane hydrate research and development programs. Government-funded scientific research drilling expeditions and production test studies have provided a wealth of information on the occurrence of methane hydrates in nature. Numerous studies have shown that the amount of gas stored as methane hydrates in the world may exceed the volume of known organic carbon sources. However, methane hydrates represent both a scientific and technical challenge, and much remains to be learned about their characteristics and occurrence in nature. Methane hydrate research in recent years has mostly focused on: (1) documenting the geologic parameters that control the occurrence and stability of methane hydrates in nature, (2) assessing the volume of natural gas stored within various methane hydrate accumulations, (3) analyzing the production response and characteristics of methane hydrates, (4) identifying and predicting natural and induced environmental and climate impacts of natural methane hydrates, (5) analyzing the methane hydrate role as a geohazard, (6) establishing the means to detect and characterize methane hydrate accumulations using geologic and geophysical data, and (7) establishing the thermodynamic phase equilibrium properties of methane hydrates as a function of temperature, pressure, and gas composition. The U.S. Department of Energy (DOE) and the Consortium for Ocean Leadership (COL) combined their efforts in 2012 to assess the contributions that scientific drilling has made and could continue to make to advance our understanding of methane hydrates in nature. COL assembled a Methane Hydrate Project Science Team with members from academia, industry, and government. This Science Team worked with COL and DOE to develop and host the Methane Hydrate Community Workshop, which surveyed a substantial cross section of the methane hydrate research community for input on the most important research developments in our understanding of methane hydrates in nature and their potential role as an energy resource, a geohazard, and/or as an agent of global climate change. Our understanding of how methane hydrates occur in nature is still growing and evolving, and it is known with certainty that field, laboratory, and modeling studies have contributed greatly to our understanding of hydrates in nature and will continue to be a critical source of the information needed to advance our understanding of methane hydrates.This is the publisher’s final pdf. The published article is copyrighted by the American Chemical Society and can be found at: http://pubs.acs.org/journal/jceaa

The neurobiology of interoception in health and disease

Interoception is the sensing of internal bodily sensations. Interoception is an umbrella term that encompasses (1) the afferent (body‐to‐brain) signaling through distinct neural and humoral (including immune and endocrine) channels; (2) the neural encoding, representation, and integration of this information concerning internal bodily state; (3) the influence of such information on other perceptions, cognitions, and behaviors; (4) and the psychological expression of these representations as consciously accessible physical sensations and feelings. Interoceptive mechanisms ensure physiological health through the cerebral coordination of homeostatic reflexes and allostatic responses that include motivational behaviors and associated affective and emotional feelings. Furthermore, the conscious, unitary sense of self in time and space may be grounded in the primacy and lifelong continuity of interoception. Body‐to‐brain interactions influence physical and mental well‐being. Consequently, we show that systematic investigation of how individual differences, and within‐individual changes, in interoceptive processing can contribute to the mechanistic understanding of physical and psychological disorders. We present a neurobiological overview of interoception and describe how interoceptive impairments at different levels relate to specific physical and mental health conditions, including sickness behaviors and fatigue, depression, eating disorders, autism, and anxiety. We frame these findings in an interoceptive predictive processing framework and highlight potential new avenues for treatments

Subjecting Elite Athletes to Inspiratory Breathing Load Reveals Behavioral and Neural Signatures of Optimal Performers in Extreme Environments

Background: It is unclear whether and how elite athletes process physiological or psychological challenges differently than healthy comparison subjects. In general, individuals optimize exercise level as it relates to differences between expected and experienced exertion, which can be conceptualized as a body prediction error. The process of computing a body prediction error involves the insular cortex, which is important for interoception, i.e. the sense of the physiological condition of the body. Thus, optimal performance may be related to efficient minimization of the body prediction error. We examined the hypothesis that elite athletes, compared to control subjects, show attenuated insular cortex activation during an aversive interoceptive challenge. Methodology/Principal Findings: Elite adventure racers (n = 10) and healthy volunteers (n = 11) performed a continuous performance task with varying degrees of a non-hypercapnic breathing load while undergoing functional magnetic resonance imaging. The results indicate that (1) non-hypercapnic inspiratory breathing load is an aversive experience associated with a profound activation of a distributed set of brain areas including bilateral insula, dorsolateral prefrontal cortex and anterior cingulated; (2) adventure racers relative to comparison subjects show greater accuracy on the continuous performance task during the aversive interoceptive condition; and (3) adventure racers show an attenuated right insula cortex response during and following the aversive interoceptive condition of non-hypercapnic inspirator

Active Inference, homeostatic regulation and adaptive behavioural control

We review a theory of homeostatic regulation and adaptive behavioural control within the Active Inference framework. Our aim is to connect two research streams that are usually considered independently; namely, Active Inference and associative learning theories of animal behaviour. The former uses a probabilistic (Bayesian) formulation of perception and action, while the latter calls on multiple (Pavlovian, habitual, goal-directed) processes for homeostatic and behavioural control. We offer a synthesis these classical processes and cast them as successive hierarchical contextualisations of sensorimotor constructs, using the generative models that underpin Active Inference. This dissolves any apparent mechanistic distinction between the optimization processes that mediate classical control or learning. Furthermore, we generalize the scope of Active Inference by emphasizing interoceptive inference and homeostatic regulation. The ensuing homeostatic (or allostatic) perspective provides an intuitive explanation for how priors act as drives or goals to enslave action, and emphasises the embodied nature of inference

Interoception in anxiety and depression

We review the literature on interoception as it relates to depression and anxiety, with a focus on belief, and alliesthesia. The connection between increased but noisy afferent interoceptive input, self-referential and belief-based states, and top-down modulation of poorly predictive signals is integrated into a neuroanatomical and processing model for depression and anxiety. The advantage of this conceptualization is the ability to specifically examine the interface between basic interoception, self-referential belief-based states, and enhanced top-down modulation to attenuate poor predictability. We conclude that depression and anxiety are not simply interoceptive disorders but are altered interoceptive states as a consequence of noisily amplified self-referential interoceptive predictive belief states

Suppression of Mcl-1 via RNA interference sensitizes human hepatocellular carcinoma cells towards apoptosis induction

BACKGROUND: Hepatocelluar carcinoma (HCC) is one of the most common cancers worldwide and a major cause of cancer-related mortality. HCC is highly resistant to currently available chemotherapeutic drugs. Defects in apoptosis signaling contribute to this resistance. Myeloid cell leukemia-1 (Mcl-1) is an anti-apoptotic member of the Bcl-2 protein family which interferes with mitochondrial activation. In a previous study we have shown that Mcl-1 is highly expressed in tissues of human HCC. In this study, we manipulated expression of the Mcl-1 protein in HCC cells by RNA interference and analyzed its impact on apoptosis sensitivity of HCC cells in vitro. METHODS: RNA interference was performed by transfecting siRNA to specifically knock down Mcl-1 expression in HCC cells. Mcl-1 expression was measured by quantitative real-time PCR and Western blot. Induction of apoptosis and caspase activity after treatment with chemotherapeutic drugs and different targeted therapies were measured by flow cytometry and fluorometric analysis, respectively. RESULTS: Here we demonstrate that Mcl-1 expressing HCC cell lines show low sensitivity towards treatment with a panel of chemotherapeutic drugs. However, treatment with the anthracycline derivative epirubicin resulted in comparatively high apoptosis rates in HCC cells. Inhibition of the kinase PI3K significantly increased apoptosis induction by chemotherapy. RNA interference efficiently downregulated Mcl-1 expression in HCC cells. Mcl-1 downregulation sensitized HCC cells to different chemotherapeutic agents. Sensitization was accompanied by profound activation of caspase-3 and -9. In addition, Mcl-1 downregulation also increased apoptosis rates after treatment with PI3K inhibitors and, to a lower extent, after treatment with mTOR, Raf I and VEGF/PDGF kinase inhibitors. TRAIL-induced apoptosis did not markedly respond to Mcl-1 knockdown. Additionally, knockdown of Mcl-1 efficiently enhanced apoptosis sensitivity towards combined treatment modalities: Mcl-1 knockdown significantly augmented apoptosis sensitivity of HCC cells towards chemotherapy combined with PI3K inhibition. CONCLUSION: Our data suggest that specific downregulation of Mcl-1 by RNA interference is a promising approach to sensitize HCC cells towards chemotherapy and molecularly targeted therapies