Erosion of the cliffs of Outer Cape Cod : tables and graphs

Originally issued as Reference No. 64-21, series later renamed WHOI-.The following tables and graphs place in convenient storage the results of several years of careful surveying and at the same time provide rudimentary interpretation of resuIts by comparing erosion rates. The reader will find listed in the bibliography pertinent published papers which analyze these coastal erosion data in great detail.This work has been supported by the Geography Branch of the Office of Naval Research, Contract Number Nonr 1254 (00), (NR-388-018), and by Nonr 2196 (00)

Development, characteristics, and effects of the new Chatham Harbor inlet

A new tidal inlet into Chatham Harbor, Massachusetts, has developed from a breach in the barrier beach, Nauset Beach, that forms the outer shoreline of southeastern Cape Cod. Increased tidal range and wave energy resulting from the new inlet produced acute coastal erosion and channel shoaling within Chatham Harbor, with significant impacts on the fishing and boating industries, and on private and public propeny and interests. Study results are consistent with the hypothesis that the Nauset-Monomoy barrier beach system undergoes a long-term cycle of geomorphological change, and that a new cycle was initiated with the formation of this new inlet. Based on this new understanding, future changes in the system can be foreseen and provided to coastal resource managers.Funding was provided by the Commonwealth of Massachusetts, Department of Environmental Management, Division of Waterways; the Town of Chatham; Woods Hole Sea Grant Program; Massachusetts Office of Coastal Zone Management; U.S. Army Corps of Engineers (New England Division and Coastal Engineering Research Center); Town of Orleans; and Friends of Pleasant Bay

Hydrodynamical Modeling of a Multiple‐Inlet Estuary/Barrier System: Insight Into Tidal Inlet Formation and Stability

Two specific questions are addressed concerning the role of tidal hydrodynamics in determining the long‐term morphologic evolution of the Nauset Beach‐Monomoy Island barrier system and the Chatham Harbor‐Pleasant Bay tidal estuary, Massachusetts: (1) why do the barrier and estuary exhibit a long‐term (∼150 yr) cycle of new inlet formation, and (2) once a new inlet forms, why is the resulting multiple inlet system unstable? To address these questions, a branched 1‐d numerical model is used to recreate the basic flow patterns in the tidal estuary at ten‐year intervals during the last half century and also to recreate flow conditions shortly before and shortly after the formation of the new inlet. Results suggest that an inlet will form through Nauset Beach once southerly elongation of the barrier has led to a critical head across the barrier at high tide. If this critical head (enhanced by storm surge and wave set‐up) exists at high tide during consecutive tidal cycles, flood currents can deepen the overwash channel sufficiently to enable the stronger ebb currents to complete the formation process. Once a new inlet has formed, the surface gradient and tidal discharge are drastically reduced along the pre‐existing channel to the south of the inlet. This reduction eliminates the tidal scouring action needed to keep the channel open. Rapid shoaling within the channel to the south of the new inlet completes the hydrodynamic decoupling of the northern and southern sections of the estuary.https://scholarworks.wm.edu/vimsbooks/1037/thumbnail.jp

Tables and graphs of measurements made across four Cape Cod beaches 1957-1958

Originally issued as Reference No. 61-4, series later renamed WHOI-.The primary purpose of this report is to present tables of measurements made across four Cape Cod beaches.The field work was supported entirely by the Geography Branch of the Office of Naval Research under contract number Nonr-1254 (00) (NR-388 - 018)

Hurricane impacts on the Caribbean coastal/marine environment : using scientific assessment to plan for the future

The passage of Hurricane Hugo through the eastern Caribbean provided a unique opportunity for multidisciplinary study of (1) the effects of severe storms on tropical coastal and marine ecosystems, and (2) the physical and biological responses of those ecosystems to intense storm-induced changes. In addition to its direct value as basic science, this study can be used to facilitate development of improved coastal and marine resource management capabilities.Funding was provided by the Andrew W. Mellon Foundation to the Coastal Research Center of the Woods Hole Oceanographic Institution (WHOI) and the NOAA National Sea Grant College Program Offce, Department of Commerce, under Grant No. NA86-AA-D-90

The intellectual disability risk gene Kdm5b regulates long term memory consolidation in the hippocampus

The histone lysine demethylase KDM5B is implicated in recessive intellectual disability disorders and heterozygous, protein truncating variants in KDM5B are associated with reduced cognitive function in the population. The KDM5 family of lysine demethylases has developmental and homeostatic functions in the brain, some of which appear to be independent of lysine demethylase activity. To determine the functions of KDM5B in hippocampus-dependent learning and memory, we first studied male and female mice homozygous for a Kdm5bΔARID allele that lacks demethylase activity. Kdm5bΔARID/ΔARID mice exhibited hyperactivity and long-term memory deficits in hippocampus-dependent learning tasks. The expression of immediate early, activity-dependent genes was downregulated in these mice and hyperactivated upon learning stimulus compared to wildtype mice. A number of other learning-associated genes was also significantly dysregulated in the Kdm5bΔARID/ΔARID hippocampus. Next, we knocked down Kdm5b specifically in the adult, wildtype mouse hippocampus with shRNA. Kdm5b knockdown resulted in spontaneous seizures, hyperactivity and hippocampus-dependent long-term memory and long-term potentiation deficits. These findings identify KDM5B as a critical regulator of gene expression and synaptic plasticity in the adult hippocampus and suggest that at least some of the cognitive phenotypes associated with KDM5B gene variants are caused by direct effects on memory consolidation mechanisms. Significance statement The histone lysine demethylase KDM5B has been implicated in cognitive performance and intellectual disability conditions in the human population. In the present manuscript we show that mice expressing a demethylase-deficient KDM5B and mice with a specific knockdown of KDM5B in the adult hippocampus exhibit hippocampus-dependent learning and memory phenotypes. Molecular analyses suggest a key role for KDM5B in regulating the dynamic expression of activity-regulated genes during memory consolidation. Deficits in LTP are present in mice with KDM5B knockdown. Together, these findings provide the first evidence for a direct function for KDM5B in memory consolidation in the hippocampus

The intellectual disability risk gene Kdm5b regulates long term memory consolidation in the hippocampus

This is the author accepted manuscript. the final version is available from the Society for Neuroscience via the DOI in this recordData availability: RNAseq data (fastq files) were deposited at the Gene Expression Omnibus (GEO) archive under the accession number GSE240887 and made freely available upon publicationThe histone lysine demethylase KDM5B is implicated in recessive intellectual disability disorders and heterozygous, protein truncating variants in KDM5B are associated with reduced cognitive function in the population. The KDM5 family of lysine demethylases has developmental and homeostatic functions in the brain, some of which appear to be independent of lysine demethylase activity. To determine the functions of KDM5B in hippocampus-dependent learning and memory, we first studied male and female mice homozygous for a Kdm5b ΔARID allele that lacks demethylase activity. Kdm5b ΔARID/ΔARID mice exhibited hyperactivity and long-term memory deficits in hippocampus-dependent learning tasks. The expression of immediate early, activity-dependent genes was downregulated in these mice and hyperactivated upon learning stimulus compared to wildtype mice. A number of other learning-associated genes was also significantly dysregulated in the Kdm5b ΔARID/ΔARID hippocampus. Next, we knocked down Kdm5b specifically in the adult, wildtype mouse hippocampus with shRNA. Kdm5b knockdown resulted in spontaneous seizures, hyperactivity and hippocampus-dependent long-term memory and long-term potentiation deficits. These findings identify KDM5B as a critical regulator of gene expression and synaptic plasticity in the adult hippocampus and suggest that at least some of the cognitive phenotypes associated with KDM5B gene variants are caused by direct effects on memory consolidation mechanisms. Significance statement The histone lysine demethylase KDM5B has been implicated in cognitive performance and intellectual disability conditions in the human population. In the present manuscript we show that mice expressing a demethylase-deficient KDM5B and mice with a specific knockdown of KDM5B in the adult hippocampus exhibit hippocampus-dependent learning and memory phenotypes. Molecular analyses suggest a key role for KDM5B in regulating the dynamic expression of activity-regulated genes during memory consolidation. Deficits in LTP are present in mice with KDM5B knockdown. Together, these findings provide the first evidence for a direct function for KDM5B in memory consolidation in the hippocampus.Medical Research Council (MRC)National Institute of AgingWellcome Trus

Shared and Distinct Functions of the Transcription Factors IRF4 and IRF8 in Myeloid Cell Development

Interferon regulatory factor (IRF) 8 and IRF4 are structurally-related, hematopoietic cell-specific transcription factors that cooperatively regulate the differentiation of dendritic cells and B cells. Whilst in myeloid cells IRF8 is known to modulate growth and differentiation, the role of IRF4 is poorly understood. In this study, we show that IRF4 has activities similar to IRF8 in regulating myeloid cell development. The ectopic expression of IRF4 in myeloid progenitor cells in vitro inhibits cell growth, promotes macrophages, but hinders granulocytic cell differentiation. We also show that IRF4 binds to and activates transcription through the IRF-Ets composite sequence (IECS). Furthermore, we demonstrate that Irf8-/-Irf4-/- mice exhibit a more severe chronic myeloid leukemia (CML)-like disease than Irf8-/- mice, involving a disproportionate expansion of granulocytes at the expense of monocytes/macrophages. Irf4-/- mice, however, display no obvious abnormality in myeloid cell development, presumably because IRF4 is expressed at a much lower level than IRF8 in granulocyte-macrophage progenitors. Our results also suggest that IRF8 and IRF4 have not only common but also specific activities in myeloid cells. Since the expression of both the IRF8 and IRF4 genes is downregulated in CML patients, these results may add to our understanding of CML pathogenesis

Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.