North Korea Presents Only Bad Options

For more about the East-West Center, see http://www.eastwestcenter.org/</a

Why North Korea's Kim Jong-un is in peace mode

For more about the East-West Center, see http://www.eastwestcenter.org/</a

Australian defence planning: five views from policy makers

The essays in this book were originally presented as speeches to the SDSC/IISS conference on The New Security Agenda in the Asia-Pacific Region, May 1996. They assess Australia's position, interests and available courses of action in the post-Cold War strategic environment. Several interesting themes emerge, including the difficulty of deciding the proper balance between various possible uses of tightly constrained defence funds; the tension between Australia's stated interest in implementing the principle of self-reliance and the country's continued dependence on its security relationship with the United States; the struggle Australia faces maintaining the Australian Defence Force's relative military capabilities in a region filled mostly with countries that are exhibiting rapid economic development and comparatively rapid upgrading of their armed forces; and Australia's interest in a stable region, even if its own capacity to bring about this outcome is limited and several potential crises are already visible on the horizon. Contributors include Australia's Minister for Defence, Minister for Foreign Affairs, Leader of the Opposition and Shadow Minister for Defence, and a senior Defence public servant. The analyses in their papers provide insights into the assumptions and attitudes within the country's policy-making circles today, perhaps foreshadowing critical decisions that will affect Australian security well into the future of this uncertain era

Direct correction of haemoglobin E β-thalassaemia using base editors

Haemoglobin E (HbE) β-thalassaemia causes approximately 50% of all severe thalassaemia worldwide; equating to around 30,000 births per year. HbE β-thalassaemia is due to a point mutation in codon 26 of the human HBB gene on one allele (GAG; glutamatic acid → AAG; lysine, E26K), and any mutation causing severe β-thalassaemia on the other. When inherited together in compound heterozygosity these mutations can cause a severe thalassaemic phenotype. However, if only one allele is mutated individuals are carriers for the respective mutation and have an asymptomatic phenotype (β-thalassaemia trait). Here we describe a base editing strategy which corrects the HbE mutation either to wildtype (WT) or a normal variant haemoglobin (E26G) known as Hb Aubenas and thereby recreates the asymptomatic trait phenotype. We have achieved editing efficiencies in excess of 90% in primary human CD34 + cells. We demonstrate editing of long-term repopulating haematopoietic stem cells (LT-HSCs) using serial xenotransplantation in NSG mice. We have profiled the off-target effects using a combination of circularization for in vitro reporting of cleavage effects by sequencing (CIRCLE-seq) and deep targeted capture and have developed machine-learning based methods to predict functional effects of candidate off-target mutations

IVOA Recommendation: Sky Event Reporting Metadata Version 2.0

VOEvent defines the content and meaning of a standard information packet for representing, transmitting, publishing and archiving information about a transient celestial event, with the implication that timely follow-up is of interest. The objective is to motivate the observation of targets-of-opportunity, to drive robotic telescopes, to trigger archive searches, and to alert the community. VOEvent is focused on the reporting of photon events, but events mediated by disparate phenomena such as neutrinos, gravitational waves, and solar or atmospheric particle bursts may also be reported. Structured data is used, rather than natural language, so that automated systems can effectively interpret VOEvent packets. Each packet may contain zero or more of the "who, what, where, when & how" of a detected event, but in addition, may contain a hypothesis (a "why") regarding the nature of the underlying physical cause of the event. Citations to previous VOEvents may be used to place each event in its correct context. Proper curation is encouraged throughout each event's life cycle from discovery through successive follow-ups. VOEvent packets gain persistent identifiers and are typically stored in databases reached via registries. VOEvent packets may therefore reference other packets in various ways. Packets are encouraged to be small and to be processed quickly. This standard does not define a transport layer or the design of clients, repositories, publishers or brokers; it does not cover policy issues such as who can publish, who can build a registry of events, who can subscribe to a particular registry, nor the intellectual property issues

Photoactivated chemotherapy (PACT) : the potential of excited-state d-block metals in medicine

The fields of phototherapy and of inorganic chemotherapy both have long histories. Inorganic photoactivated chemotherapy (PACT) offers both temporal and spatial control over drug activation and has remarkable potential for the treatment of cancer. Following photoexcitation, a number of different decay pathways (both photophysical and photochemical) are available to a metal complex. These pathways can result in radiative energy release, loss of ligands or transfer of energy to another species, such as triplet oxygen. We discuss the features which need to be considered when developing a metal-based anticancer drug, and the common mechanisms by which the current complexes are believed to operate. We then provide a comprehensive overview of PACT developments for complexes of the different d-block metals for the treatment of cancer, detailing the more established areas concerning Ti, V, Cr, Mn, Re, Fe, Ru, Os, Co, Rh, Pt, and Cu and also highlighting areas where there is potential for greater exploration. Nanoparticles (Ag, Au) and quantum dots (Cd) are also discussed for their photothermal destructive potential. We also discuss the potential held in particular by mixed-metal systems and Ru complexes

A Mediterranean Diet and Walking Intervention to Reduce Cognitive Decline and Dementia Risk in Independently Living Older Australians:The MedWalk Randomized Controlled Trial Experimental Protocol, Including COVID-19 Related Modifications and Baseline Characteristics.

Background:Several clinical trials have examined diet and physical activity lifestyle changes as mitigation strategies for risk factors linked to cognitive decline and dementias such as Alzheimer’s disease. However, the ability to modify these behaviors longer term, to impact cognitive health has remained elusive.Objective:The MedWalk trial’s primary aim is to investigate whether longer-term adherence to a Mediterranean-style diet and regular walking, delivered through motivational interviewing and cognitive-behavioral therapy (MI-CBT), can reduce age-associated cognitive decline and other dementia risk factors in older, independently living individuals without cognitive impairment.Methods:MedWalk, a one-year cluster-randomized controlled trial across two Australian states, recruited 60–90-year-old people from independent living retirement villages and the wider community. Participants were assigned to either the MedWalk intervention or a control group (maintaining their usual diet and physical activity). The primary outcome is 12-month change in visual memory and learning assessed from errors on the Paired Associates Learning Task of the Cambridge Neuropsychological Test Automated Battery. Secondary outcomes include cognition, mood, cardiovascular function, biomarkers related to nutrient status and cognitive decline, MI-CBT effectiveness, Mediterranean diet adherence, physical activity, quality of life, cost-effectiveness, and health economic evaluation.Progress and Discussion:Although COVID-19 impacts over two years necessitated a reduced timeline and sample size, MedWalk retains sufficient power to address its aims and hypotheses. Baseline testing has been completed with 157 participants, who will be followed over 12 months. If successful, MedWalk will inform interventions that could substantially reduce dementia incidence and ameliorate cognitive decline in the community.<br/

The relationships between health information behavior and neural processing in african americans with prehypertension

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/150533/1/asi24098_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/150533/2/asi24098.pd

Acyl-Protein Thioesterase 2 Catalizes the Deacylation of Peripheral Membrane-Associated GAP-43

An acylation/deacylation cycle is necessary to maintain the steady-state subcellular distribution and biological activity of S-acylated peripheral proteins. Despite the progress that has been made in identifying and characterizing palmitoyltransferases (PATs), much less is known about the thioesterases involved in protein deacylation. In this work, we investigated the deacylation of growth-associated protein-43 (GAP-43), a dually acylated protein at cysteine residues 3 and 4. Using fluorescent fusion constructs, we measured in vivo the rate of deacylation of GAP-43 and its single acylated mutants in Chinese hamster ovary (CHO)-K1 and human HeLa cells. Biochemical and live cell imaging experiments demonstrated that single acylated mutants were completely deacylated with similar kinetic in both cell types. By RT-PCR we observed that acyl-protein thioesterase 1 (APT-1), the only bona fide thioesterase shown to mediate deacylation in vivo, is expressed in HeLa cells, but not in CHO-K1 cells. However, APT-1 overexpression neither increased the deacylation rate of single acylated GAP-43 nor affected the steady-state subcellular distribution of dually acylated GAP-43 both in CHO-K1 and HeLa cells, indicating that GAP-43 deacylation is not mediated by APT-1. Accordingly, we performed a bioinformatic search to identify putative candidates with acyl-protein thioesterase activity. Among several candidates, we found that APT-2 is expressed both in CHO-K1 and HeLa cells and its overexpression increased the deacylation rate of single acylated GAP-43 and affected the steady-state localization of diacylated GAP-43 and H-Ras. Thus, the results demonstrate that APT-2 is the protein thioesterase involved in the acylation/deacylation cycle operating in GAP-43 subcellular distribution

Skeletal evidence for variable patterns of handedness in chimpanzees, human hunter–gatherers, and recent British populations

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/98285/1/nyas12067.pd