Coastal oceanography and sedimentology in New Zealand, 1967-91.

This paper reviews research that has taken place on physical oceanography and sedimentology on New Zealand's estuaries and the inner shelf since c. 1967. It includes estuarine sedimentation, tidal inlets, beach morphodynamics, nearshore and inner shelf sedimentation, tides and coastal currents, numerical modelling, short-period waves, tsunamis, and storm surges. An extensive reference list covering both published and unpublished material is included. Formal teaching and research programmes dealing with coastal landforms and the processes that shape them were only introduced to New Zealand universities in 1964; the history of the New Zealand Journal of Marine and Freshwater Research parallels and chronicles the development of physical coastal science in New Zealand, most of which has been accomplished in last 25 years

Development of the circadian system in early life: maternal and environmental factors

In humans, an adaptable internal biological system generates circadian rhythms that maintain synchronicity of behavior and physiology with the changing demands of the 24-h environment. Development of the circadian system begins in utero and continues throughout the first few years of life. Maturation of the clock can be measured through sleep/wake patterns and hormone secretion. Circadian rhythms, by definition, can persist in the absence of environmental input; however, their ability to adjust to external time cues is vital for adaptation and entrainment to the environment. The significance of these external factors that influence the emergence of a stable circadian clock in the first years of life remain poorly understood. Infants raised in our post-modern world face adverse external circadian signals, such as artificial light and mistimed hormonal cues via breast milk, which may increase interference with the physiological mechanisms that promote circadian synchronization. This review describes the very early developmental stages of the clock and common circadian misalignment scenarios that make the developing circadian system more susceptible to conflicting time cues and temporal disorder between the maternal, fetal, infant, and peripheral clocks

DESIGN, DEVELOPMENT AND FIELD DEPLOYMENT OF A TELEOPERATED SAMPLING SYSTEM

A teleoperated sampling system for the identification, collection and retrieval of samples following the detonation of an Improvised Nuclear Device (IND) or Radiological Dispersion Devise (RDD) has been developed and tested in numerous field exercises. The system has been developed as part of the Defense Threat Reduction Agency's (DTRA) National Technical Nuclear Forensic (NTNF) Program. The system is based on a Remotec ANDROS Mark V-A1 platform. Extensive modifications and additions have been incorporated into the platform to enable it to meet the mission requirements. The Defense Science Board Task Force on Unconventional Nuclear Warfare Defense, 2000 Summer Study Volume III report recommended the Department of Defense (DOD) improve nuclear forensics capabilities to achieve accurate and fast identification and attribution. One of the strongest elements of protection is deterrence through the threat of reprisal, but to accomplish this objective a more rapid and authoritative attribution system is needed. The NTNF program provides the capability for attribution. Early on in the NTNF program, it was recognized that there would be a desire to collect debris samples for analysis as soon as possible after a nuclear event. Based on nuclear test experience, it was recognized that mean radiation fields associated with even low yield events could be several thousand R/Hr near the detonation point for some time after the detonation. In anticipation of pressures to rapidly sample debris near the crater, considerable effort is being devoted to developing a remotely controlled vehicle that could enter the high radiation field area and collect one or more samples for subsequent analysis

The Effector Domain of MARCKS Is a Nuclear Localization Signal that Regulates Cellular PIP2 Levels and Nuclear PIP2 Localization

Translocation to the nucleus of diacylglycerol kinase (DGK)– ζ is dependent on a sequence homologous to the effector domain of Myristoylated Alanine Rich C-Kinase Substrate (MARCKS). These data would suggest that MARCKS could also localize to the nucleus. A single report demonstrated immunofluorescence staining of MARCKS in the nucleus; however, further experimental evidence confirming the specific domain responsible for this localization has not been reported. Here, we report that MARCKS is present in the nucleus in GBM cell lines. We then over-expressed wild-type MARCKS (WT) and MARCKS with the effector domain deleted (ΔED), both tagged with V5-epitope in a GBM cell line with low endogenous MARCKS expression (U87). We found that MARCKS-WT localized to the nucleus, while the MARCKS construct without the effector domain remained in the cytoplasm. We also found that over-expression of MARCKS-WT resulted in a significant increase in total cellular phosphatidyl-inositol (4,5) bisphosphate (PIP2) levels, consistent with prior evidence that MARCKS can regulate PIP2 levels. We also found increased staining for PIP2 in the nucleus with MARCKS-WT over-expression compared to MARCKS ΔED by immunofluorescence. Interestingly, we observed MARCKS and PIP2 co-localization in the nucleus. Lastly, we found changes in gene expression when MARCKS was not present in the nucleus (MARCKS ΔED). These data indicate that the MARCKS effector domain can function as a nuclear localization signal and that this sequence is critical for the ability of MARCKS to regulate PIP2 levels, nuclear localization, and gene expression. These data suggests a novel role for MARCKS in regulating nuclear functions such as gene expression

MARCKS phosphorylation is modulated by a peptide mimetic of MARCKS effector domain leading to increased radiation sensitivity in lung cancer cell lines

Lung cancer is the leading cause of cancer-associated mortality in the United States. Kinase hyperactivation is a known mechanism of tumorigenesis. The phosphorylation status of the plasma membrane-associated protein myristoylated alanine rich C-kinase substrate (MARCKS) effector domain (ED) was previously established as being important in the sensitivity of lung cancer to radiation. Specifically, when MARCKS ED was in a non-phosphorylated state, lung cancer cells were more susceptible to ionizing radiation and experienced prolonged double-strand DNA breaks. Additional studies demonstrated that the phosphorylation status of MARCKS ED is important for gene expression and in vivo tumor growth. The present study used a peptide mimetic of MARCKS ED as a therapeutic intervention to modulate MARCKS phosphorylation. Culturing A549, H1792 and H1975 lung cancer cell lines with the MARCKS ED peptide led to reduced levels of phosphorylated MARCKS and phosphorylated Akt serine/threonine kinase 1. Further investigation demonstrated that the peptide therapy was able to reduce lung cancer cell proliferation and increase radiation sensitivity. In addition, the MARCKS peptide therapy was able to prolong double-strand DNA breaks following ionizing radiation exposure. The results of the present study demonstrate that a peptide mimetic of MARCKS ED is able to modulate MARCKS phosphorylation, leading to an increase in sensitivity to radiation. Keywords: lung cancer, myristoylated alanine rich C-kinase substrate, radiation sensitivity, effector domain, peptide mimeti

Discovery of an intermediate-luminosity red transient in M51 and its likely dust-obscured, infrared-variable progenitor

We present the discovery of an optical transient (OT) in Messier 51, designated M51 OT2019-1 (also ZTF19aadyppr, AT 2019abn, ATLAS19bzl), by the Zwicky Transient Facility (ZTF). The OT rose over 15 days to an observed luminosity of $M_r=-13$ (${\nu}L_{\nu}=9\times10^6~L_{\odot}$), in the luminosity gap between novae and typical supernovae (SNe). Spectra during the outburst show a red continuum, Balmer emission with a velocity width of $\approx400$ km s$^{-1}$, Ca II and [Ca II] emission, and absorption features characteristic of an F-type supergiant. The spectra and multiband light curves are similar to the so-called "SN impostors" and intermediate-luminosity red transients (ILRTs). We directly identify the likely progenitor in archival Spitzer Space Telescope imaging with a $4.5~\mu$m luminosity of $M_{[4.5]}\approx-12.2$ and a $[3.6]-[4.5]$ color redder than 0.74 mag, similar to those of the prototype ILRTs SN 2008S and NGC 300 OT2008-1. Intensive monitoring of M51 with Spitzer further reveals evidence for variability of the progenitor candidate at [4.5] in the years before the OT. The progenitor is not detected in pre-outburst Hubble Space Telescope optical and near-IR images. The optical colors during outburst combined with spectroscopic temperature constraints imply a higher reddening of $E(B-V)\approx0.7$ mag and higher intrinsic luminosity of $M_r\approx-14.9$ (${\nu}L_{\nu}=5.3\times10^7~L_{\odot}$) near peak than seen in previous ILRT candidates. Moreover, the extinction estimate is higher on the rise than on the plateau, suggestive of an extended phase of circumstellar dust destruction. These results, enabled by the early discovery of M51 OT2019-1 and extensive pre-outburst archival coverage, offer new clues about the debated origins of ILRTs and may challenge the hypothesis that they arise from the electron-capture induced collapse of extreme asymptotic giant branch stars.Comment: 21 pages, 5 figures, published in ApJ

Experience With the Cardiac Surgery Simulation Curriculum: Results of the Resident and Faculty Survey

BACKGROUND: The Cardiac Surgery Simulation Curriculum was developed at 8 institutions from 2010 to 2013. A total of 27 residents were trained by 18 faculty members. A survey was conducted to gain insight into the initial experience. METHODS: Residents and faculty were sent a 72- and 68-question survey, respectively. In addition to demographic information, participants reported their view of the overall impact of the curriculum. Focused investigation into each of the 6 modules was obtained. Participants evaluated the value of the specific simulators used. Institutional biases regarding implementation of the curriculum were evaluated. RESULTS: Twenty (74%) residents and 14 (78%) faculty responded. The majority (70%) of residents completed this training in their first and second year of traditional-track programs. The modules were well regarded with no respondents having an unfavorable view. Both residents and faculty found low, moderate, and high fidelity simulators to be extremely useful, with particular emphasis on utility of high fidelity components. The vast majority of residents (85%) and faculty (100%) felt more comfortable in the resident skill set and performance in the operating room. Simulation of rare adverse events allowed for development of multidisciplinary teams to address them. At most institutions, the conduct of this curriculum took precedence over clinical obligations (64%). CONCLUSIONS: The Cardiac Surgery Simulation Curriculum was implemented with robust adoption among the investigating centers. Both residents and faculty viewed the modules favorably. Using this curriculum, participants indicated an improvement in resident technical skills and were enthusiastic about training in adverse events and crisis management

Human intestinal tissue tropism of intimin epsilon O103 Escherichia coli

Human intestinal in vitro organ culture was used to assess the tissue tropism of human isolates of Escherichia coli O103:H2 and O103:H- that express intimin F. Both strains showed tropism for follicle associated epithelium and limited adhesion to other regions of the small and large intestine. This is similar to the tissue tropism shown by intimin gamma enterohaemorrhagic (EHEC) O157:H7, but distinct from that of intimin a enteropathogenic (EPEC) O127:H6. (C) 2002 Federation of European Microbiological Societies. Published by Elsevier Science B.V. All rights reserve

Targeting the effector domain of the myristoylated alanine rich C-kinase substrate enhances lung cancer radiation sensitivity

Lung cancer is the leading cause of cancer related deaths. Common molecular drivers of lung cancer are mutations in receptor tyrosine kinases (RTKs) leading to activation of the phosphatidylinositol 3-kinase (PI3K)/Akt pro-growth, pro-survival signaling pathways. Myristoylated alanine rich C-kinase substrate (MARCKS) is a protein that has the ability to mitigate this signaling cascade by sequestering the target of PI3K, phosphatidylinositol (4,5)-bisphosphate (PIP2). As such, MARCKS has been implicated as a tumor suppressor, though there is some evidence that MARCKS may be tumor promoting in certain cancer types. Since the MARCKS function depends on its phosphorylation status, which impacts its subcellular location, MARCKS role in cancer may depend highly on the signaling context. Currently, the importance of MARCKS in lung cancer biology is limited. Thus, we investigated MARCKS in both clinical specimens and cell culture models. Immunohistochemistry scoring of MARCKS protein expression in a diverse lung tumor tissue array revealed that the majority of squamous cell carcinomas stained positive for MARCKS while other histologies, such as adenocarcinomas, had lower levels. To study the importance of MARCKS in lung cancer biology, we used inducible overexpression of wild-type (WT) and non-phosphorylatable (NP)-MARCKS in A549 lung cancer cells that had a low level of endogenous MARCKS. We found that NP-MARCKS expression, but not WT-MARCKS, enhanced the radiosensitivity of A549 cells in part by inhibiting DNA repair as evidenced by prolonged radiation-induced DNA double strand breaks. We confirmed the importance of MARCKS phosphorylation status by treating several lung cancer cell lines with a peptide mimetic of the phosphorylation domain, the effector domain (ED), which effectively attenuated cell growth as measured by cell index. Thus, the MARCKS ED appears to be an important target for lung cancer therapeutic development

'Tough'-constructions and their derivation

This article addresses the syntax of the notorious 'tough' (-movement) construction (TC) in English. TCs exhibit a range of apparently contradictory empirical properties suggesting that their derivation involves the application of both A-movement and A'-movement operations. Given that within previous Principles and Parameters models TCs have remained “unexplained and in principle unexplainable” (Holmberg 2000: 839) due to incompatibility with constraints on theta-assignment, locality, and Case, this article argues that the phase-based implementation of the Minimalist program (Chomsky 2000, 2001, 2004) permits a reanalysis of null wh-operators capable of circumventing the previous theoretical difficulties. Essentially, 'tough'-movement consists of A-moving a constituent out of a “complex” null operator which has already undergone A'-movement, a “smuggling” construction in the terms of Collins (2005a,b