Taming Troubled Waters: Joint Development of Oil and Mineral Resources in Overlapping Claim Areas

This Article examines the issues surrounding the joint development of resources in overlapping claim areas. The author reviews the precedents for joint development of offshore areas and seeks to define the elements that frequently appear in these precedents, namely the extent of the area, the contract type, the financial arrangements, the process of selection of concessionaires or operators, the length of the agreement, and the nature and functions of the joint management body. The author also examines the joint development efforts of various countries which share common claimed resources. The author argues that the success of joint development agreements depends on the given knowledge of actual deposits, good political relations, practical mindedness, and cooperative private companies

A Marine Security Regime for Northeast Asia

The Article describes a regional security mechanism in Northeast Asia. This mechanism should originally focus on maritime security. The rationale includes the region’s geography, competing maritime and island claims, the resultant maritime military buildup and changing priorities, increasing frequency of dangerous incidents, and the existence of a foundation for conflict avoidance and resource sharing. The Declaration on the Conduct of Parties in the South China Sea could serve as a model for a similar Declaration for Northeast Asian Seas that may ultimately include guidelines for activities in others’ Exclusive Economic Zones

BUMPER v1.0: a Bayesian user-friendly model for palaeo-environmental reconstruction

We describe the Bayesian user-friendly model for palaeo-environmental reconstruction (BUMPER), a Bayesian transfer function for inferring past climate and other environmental variables from microfossil assemblages. BUMPER is fully self-calibrating, straightforward to apply, and computationally fast, requiring ~2 s to build a 100-taxon model from a 100-site training set on a standard personal computer. We apply the model’s probabilistic framework to generate thousands of artificial training sets under ideal assumptions.We then use these to demonstrate the sensitivity of reconstructions to the characteristics of the training set, considering assemblage richness, taxon tolerances, and the number of training sites. We find that a useful guideline for the size of a training set is to provide, on average, at least 10 samples of each taxon. We demonstrate general applicability to real data, considering three different organism types (chironomids, diatoms, pollen) and different reconstructed variables. An identically configured model is used in each application, the only change being the input files that provide the training-set environment and taxon-count data. The performance of BUMPER is shown to be comparable with weighted average partial least squares (WAPLS) in each case. Additional artificial datasets are constructed with similar characteristics to the real data, and these are used to explore the reasons for the differing performances of the different training sets

Effects of Ascent to High Altitude on Human Antimycobacterial Immunity

Backgroun

Lorcaserin improves glycemic control via a melanocortin neurocircuit.

OBJECTIVE: The increasing prevalence of type 2 diabetes (T2D) and associated morbidity and mortality emphasizes the need for a more complete understanding of the mechanisms mediating glucose homeostasis to accelerate the identification of new medications. Recent reports indicate that the obesity medication lorcaserin, a 5-hydroxytryptamine (5-HT, serotonin) 2C receptor (5-HT2CR) agonist, improves glycemic control in association with weight loss in obese patients with T2D. Here we evaluate whether lorcaserin has an effect on glycemia without body weight loss and how this effect is achieved. METHODS: Murine models of common and genetic T2D were utilized to probe the direct effect of lorcaserin on glycemic control. RESULTS: Lorcaserin dose-dependently improves glycemic control in mouse models of T2D in the absence of reductions in food intake or body weight. Examining the mechanism of this effect, we reveal a necessary and sufficient neurochemical mediator of lorcaserin's glucoregulatory effects, brain pro-opiomelanocortin (POMC) peptides. To clarify further lorcaserin's therapeutic brain circuit, we examined the receptor target of POMC peptides. We demonstrate that lorcaserin requires functional melanocortin4 receptors on cholinergic preganglionic neurons (MC4RChAT) to exert its effects on glucose homeostasis. In contrast, MC4RChAT signaling did not impact lorcaserin's effects on feeding, indicating a divergence in the neurocircuitry underpinning lorcaserin's therapeutic glycemic and anorectic effects. Hyperinsulinemic-euglycemic clamp studies reveal that lorcaserin reduces hepatic glucose production, increases glucose disposal and improves insulin sensitivity. CONCLUSIONS: These data suggest that lorcaserin's action within the brain represents a mechanistically novel treatment for T2D: findings of significance to a prevalent global disease

DNA Methylation Profiles and Their Relationship with Cytogenetic Status in Adult Acute Myeloid Leukemia

Background: Aberrant promoter DNA methylation has been shown to play a role in acute myeloid leukemia (AML) pathophysiology. However, further studies to discuss the prognostic value and the relationship of the epigenetic signatures with defined genomic rearrangements in acute myeloid leukemia are required. Methodology/Principal Findings: We carried out high-throughput methylation profiling on 116 de novo AML cases and we validated the significant biomarkers in an independent cohort of 244 AML cases. Methylation signatures were associated with the presence of a specific cytogenetic status. In normal karyotype cases, aberrant methylation of the promoter of DBC1 was validated as a predictor of the disease-free and overall survival. Furthermore, DBC1 expression was significantly silenced in the aberrantly methylated samples. Patients with chromosome rearrangements showed distinct methylation signatures. To establish the role of fusion proteins in the epigenetic profiles, 20 additional samples of human hematopoietic stem/ progenitor cells (HSPC) transduced with common fusion genes were studied and compared with patient samples carrying the same rearrangements. The presence of MLL rearrangements in HSPC induced the methylation profile observed in the MLL-positive primary samples. In contrast, fusion genes such as AML1/ETO or CBFB/MYH11 failed to reproduce the epigenetic signature observed in the patients. Conclusions/Significance: Our study provides a comprehensive epigenetic profiling of AML, identifies new clinical markers for cases with a normal karyotype, and reveals relevant biological information related to the role of fusion proteins on the methylation signatur

Keys of a Mission to Uranus or Neptune, the Closest Ice Giants

Uranus and Neptune are the archetypes of "ice giants", a class of planets that may be among the most common in the Galaxy. They are the last unexplored planets of the Solar System, yet they hold the keys to understand the atmospheric dynamics and structure of planets with hydrogen atmospheres inside and outside the solar system