Ships in Distress,Environmental Threats to Coastal States,and Places of Refuge: New Directions for an Ancien Regime ?

Places of refuge for ships in distress is a topic before the International Maritime Organization as a result of several recent well-publicized refusals by maritime authorities of coastal states to allow such ships to enter sheltered waters within national jurisdiction. The traditional right of refuge of the crew, ship, and cargo is pitted against threat perceptions held by coastal states resulting in a "not in my backyard" syndrome. Instances of modern state practice seem to restrict the right of refuge to a purely humanitarian dimension. There is a need to reevaluate the right of refuge and to establish a system of places of refuge on the basis of regional cooperation to counter the potential threat of stricken ships that are unable to effect necessary repairs in sheltered areas within national jurisdiction.     

The nostalgic construction of community: Memory and social identity in Urban Malta

This paper examines local people's memories of a Maltese urban community that was demolished in the 1970s. The memories create an idealised, nostalgic picture of community harmony and solidarity prior to the demolition, but also apportion blame for its subsequent destruction. The paper argues that in such situations of physical displacement and/or social dislocation, this nostalgic process serves as a strategic resource that not only produces order and identity, but also creates legitimate moral claims against the state. The paper thereby contributes to ongoing debates about the relationship between local identity and wider political and economic processes.     

Observer-based tracking control of abnormal oscillations in demyelination symptom

Fast axonal conduction of action potentials in mammals relies on myelin insulation. Demyelination can cause slowed, blocked, desynchronized, or paradoxically excessive spiking that underlies the symptoms observed in demyelination diseases. Feedback control via functional electrical stimulation (FES) seems to be a promising treatment modality in such diseases. However, there are challenges to implementing such method for neurons: high nonlinearity, biological tissue constrains and unobservable ion channel states. To address this problem, we propose an estimating and tracking control strategy for systems based on Kalman filter, in order to enhance the action potential propagation reliability of demyelinated neuron via FES. Unscented Kalman filter (UKF) is employed to estimate the unobservable states and parameters in the demyelination neuron model from membrane potential dynamics. Our method could promote the design of new closed-loop electrical stimulation systems for patients suffering from different nerve system dysfunctions.     

Focus: The Aging Brain: The Significance of the Default Mode Network (DMN) in Neurological and Neuropsychiatric Disorders: A Review

The relationship of cortical structure and specific neuronal circuitry to global brain function, particularly its perturbations related to the development and progression of neuropathology, is an area of great interest in neurobehavioral science. Disruption of these neural networks can be associated with a wide range of neurological and neuropsychiatric disorders. Herein we review activity of the Default Mode Network (DMN) in neurological and neuropsychiatric disorders, including Alzheimer’s disease, Parkinson’s disease, Epilepsy (Temporal Lobe Epilepsy - TLE), attention deficit hyperactivity disorder (ADHD), and mood disorders. We discuss the implications of DMN disruptions and their relationship to the neurocognitive model of each disease entity, the utility of DMN assessment in clinical evaluation, and the changes of the DMN following treatment.     

Stability,sensitivity and uncertainty rates in the flow equations of ecological models

In previous work by the authors about dynamic system modeling, basic ecosystems concepts and their application to ecological modeling theory were formalized. Measuring how a variable effects certain processes leads to improvements in dynamic systems modelling and facilitates the author’s study of system diversity in which model sensitivity is a key theme. Initially, some variables and their numeric data are used for modeling. Predictions from the constructed models depend on these data. Generic study of sensitivity aims to show to what degree model behavior is altered by modification of some specific data. If small variations cause important modifications in the model’s global behavior then the model is very sensitive in relation to the variables used. If uncertain systems are considered, then it is important to submit the system to extreme situations and analyze its behavior. In this article, some indexes of uncertainty will be defined in order to determine the variables' influence in the case of extreme changes. This will permit analysis of the system’s sensitivity in relation to several simulations.     

Synthesis and evaluation of 1,3,5-triazine derivatives as sunscreens useful to prevent skin cancer

The incidence of skin cancers such as non-melanoma skin cancer and malignant melanoma has increased in the last few years mainly because of chronic exposure to ultraviolet (UV) radiation. Sunscreens protect the skin against harmful UV radiations; however, some limitations of these products justify the discovery of new UV filters. Novel 1,3,5-triazine derivatives (12a-h) obtained by the optimization of prototype resveratrol were synthesized and characterized. All compounds exhibited sun protection factor (SPF) and UVA protection factor (UVAPF) in the range of 3–17 and 3–13, respectively. These values were superior to resveratrol and the UV filter ethylhexyl triazone (EHT) currently available on the market. In addition, all compounds demonstrated in vitro antioxidant activity and thermal stability with the decomposition at temperatures above 236 °C. In conclusion, the novel 1,3,5-triazine derivatives have emerged as new UV filters with antioxidant effect useful to prevent skin cancer.     

Synthesis and biological evaluation of PSMA-targeting paclitaxel conjugates

Prostate cancer (PC) is the second most commonly occurring cancer in men. Conventional chemotherapy has wide variety of disadvantages such as high systemic toxicity and low selectivity. Targeted drug delivery is a promising approach to decrease side effects of therapy. Prostate specific membrane antigen (PSMA) is overexpressed in prostate cancer cells while low level of expression is observed in normal cells. In this study we describe the development of Glu-urea-Lys based PSMA-targeting conjugates with paclitaxel. A series of new PSMA targeting conjugates with paclitaxel was designed and synthesized. The cytotoxicity of conjugates was evaluated against prostate (LNCaP, 22Rv1 and PC-3) and non-prostate (Hek293T, VA13, A549 and MCF-7) cell lines. The most promising conjugate 21 was examined in vivo using 22Rv1 xenograft mice model. It demonstrated good efficiency comparable with paclitaxel, while reduced toxicity. 3D molecular docking study was also performed to understand underlying mechanism of binding and further optimization of the linker substructure and conjugates structure for improving the target affinity. These conjugates may be useful for further design of novel PSMA targeting delivery systems for PC.     

Factors associated with black bear density and implications for management

Wildlife density estimates are important to accurately formulate population management objectives and understand the relationship between habitat characteristics and a species’ abundance. Despite advances in density and abundance estimation methods, management of common game species continues to be challenged by a lack of reliable population estimates. In Washington, USA, statewide American black bear (Ursus americanus) abundance estimates are predicated on density estimates derived from research in the 1970s and are hypothesized to be a function of precipitation and vegetation, with higher densities in western Washington. To evaluate current black bear density and landscape relationships in Washington, we conducted a 4-year capture-recapture study in 2 areas of the North Cascade Mountains using 2 detection methods, non-invasive DNA collection and physical capture and deployment of global positioning system (GPS) collars. We integrated GPS telemetry from collared bears with spatial capture-recapture (SCR) data and created a SCR-resource selection model to estimate density as a function of spatial covariates and test the hypothesis that density is higher in areas with greater vegetative food resources. We captured and collared 118 bears 132 times and collected 7,863 hair samples at hair traps where we identified 537 bears from 1,237 detections via DNA. The most-supported model in the western North Cascades depicted a negative relationship between black bear density and an index of human development. We estimated bear density at 20.1 bears/100 km², but density varied from 13.5/100 km² to 27.8 bears/100 km² depending on degree of human development. The model best supported by the data in the eastern North Cascades estimated an average density of 19.2 bears/100 km², which was positively correlated with primary productivity, with resulting density estimates ranging from 7.1/100 km² to 33.6 bears/100 km². The hypothesis that greater precipitation and associated vegetative production in western Washington supports greater bear density compared to eastern Washington was not supported by our data. In western Washington, empirically derived average density estimates (including cubs) were nearly 50% lower than managers expected prior to our research. In eastern Washington average black bear density was predominantly as expected, but localized areas of high primary productivity supported greater than anticipated bear densities. Our findings underscore the importance that black bear density is not likely uniform and management risk may be increased if an average density is applied at too large a scale. Disparities between expected and empirically derived bear density illustrate the need for more rigorous monitoring to understand processes that affect population numbers throughout the jurisdiction, and suggest that management plans may need to be reevaluated to determine if current harvest strategies are achieving population objectives. © 2019 The Wildlife Society.     

Small-angle neutron and X-ray scattering analysis of the supramolecular organization of rhodopsin in photoreceptor membrane

The supramolecular organization of the visual pigment rhodopsin in the photoreceptor membrane remains contentious. Specifically, whether this G protein-coupled receptor functions as a monomer or dimer remains unknown, as does the presence or absence of ordered packing of rhodopsin molecules in the photoreceptor membrane. Completely opposite opinions have been expressed on both issues. Herein, using small-angle neutron and X-ray scattering approaches, we performed a comparative analysis of the structural characteristics of the photoreceptor membrane samples in buffer, both in the outer segment of photoreceptor cells, and in the free photoreceptor disks. The average distance between the centers of two neighboring rhodopsin molecules was found to be ~5.8 nm in both cases. The results indicate an unusually high packing density of rhodopsin molecules in the photoreceptor membrane, but molecules appear to be randomly distributed in the membrane without any regular ordering.     

Potential roles and targeted therapy of the CXCLs/CXCR2 axis in cancer and inflammatory diseases

The chemokine receptor CXCR2 and its ligands are implicated in the progression of tumours and various inflammatory diseases. Activation of the CXCLs/CXCR2 axis activates multiple signalling pathways, including the PI3K, p38/ERK, and JAK pathways, and regulates cell survival and migration. The CXCLs/CXCR2 axis plays a vital role in the tumour microenvironment and in recruiting neutrophils to inflammatory sites. Extensive infiltration of neutrophils during chronic inflammation is one of the most important pathogenic factors in various inflammatory diseases. Chronic inflammation is considered to be closely correlated with initiation of cancer. In addition, immunosuppressive effects of myeloid-derived suppressor cells (MDSCs) against T cells attenuate the anti-tumour effects of T cells and promote tumour invasion and metastasis. Over the last several decades, many therapeutic strategies targeting CXCR2 have shown promising results and entered clinical trials. In this review, we focus on the features and functions of the CXCLs/CXCR2 axis and highlight its role in cancer and inflammatory diseases. We also discuss its potential use in targeted therapies.