Location Analysis of Lifestyle Centers: Uncovering Patterns and Potential Driving Factors behind Site Selection

The shopping center has held an important place in the American economy for decades. However, the concept has seen multiple revolution in terms of format. The most recent shopping center concept to gain rapid popularity is the lifestyle center – an outdoor shopping mall made to resemble a pleasant main street setting, with a tenant mix emphasizing dining and entertainment. In other words, the lifestyle center concept is geared toward selling consumers things to do, versus things to buy. This thesis studies the geography of lifestyle centers in the United States in both the large-scale and small-scale view. Results show that lifestyle centers are concentrated into larger urban areas, often with a population of over 1 million. An analysis of spatial agglomeration revealed that lifestyle centers are often several miles away from the nearest traditional mall, indicating that developers do not feel the need to build near established shopping districts where traditional malls lie. Finally, results concerning trade area characteristics show the characteristics of consumers in areas where lifestyle centers have been built. Findings in this study indicate that developers are utilizing a unique approach when selecting sites for lifestyle centers compared to traditional indoor malls

Histone H3K36 methylation regulates pre-mRNA splicing in Saccharomyces cerevisiae

Co-transcriptional splicing takes place in the context of a highly dynamic chromatin architecture, yet the role of chromatin restructuring in coordinating transcription with RNA splicing has not been fully resolved. To further define the contribution of histone modifications to pre-mRNA splicing in Saccharomyces cerevisiae, we probed a library of histone point mutants using a reporter to monitor pre-mRNA splicing. We found that mutation of H3 lysine 36 (H3K36) – a residue methylated by Set2 during transcription elongation – exhibited phenotypes similar to those of pre-mRNA splicing mutants. We identified genetic interactions between genes encoding RNA splicing factors and genes encoding the H3K36 methyltransferase Set2 and the demethylase Jhd1 as well as point mutations of H3K36 that block methylation. Consistent with the genetic interactions, deletion of SET2, mutations modifying the catalytic activity of Set2 or H3K36 point mutations significantly altered expression of our reporter and reduced splicing of endogenous introns. These effects were dependent on the association of Set2 with RNA polymerase II and H3K36 dimethylation. Additionally, we found that deletion of SET2 reduces the association of the U2 and U5 snRNPs with chromatin. Thus, our study provides the first evidence that H3K36 methylation plays a role in co-transcriptional RNA splicing in yeast

Discriminación por razón de género y negociación colectiva tras la ley 3/2012

Este artículo describe y analiza la configuración jurídica del convenio colectivo como fuente reguladora y ga-rantista del derecho de igualdad y no dis-criminación por razón de género, tanto con carácter general como en el ámbito específico del acceso al empleo, formación y promoción en el trabajo y en las más relevantes condiciones en las relaciones laborales. A tal fin, y a partir de la doctrina establecida por la jurisprudencia constitucional, se estudian las causas de la desigualdad y las categorías que permiten una fundamentación razonable y objetiva para lograr la igualdad material. También se aportan datos cuantitativos acerca de la influencia de la Ley Orgánica 3/2007 en el régimen de los convenios convenios colectivos en esta materia.This paper work de-scribes and analyses the collective agree-ments legal configuration as regulating and guarantor source of the equality's right and no discrimination because of the sex, as much in general terms as in the specific field of accessing to a job, training and advance-ment in the job and in the main conditions in the labour relationships. According the established doctrine by the constitutional sentences, we study the inequality causes and the categories which give a reasonable and factual basis to reach a material equality. In addition, this work also provides quanti-tative facts about the influence of Organic Law 3/2007 in the collective agreements regime in this matte

Defective cancellous bone structure and abnormal response to PTH in cortical bone of mice lacking Cx43 cytoplasmic C-terminus domain

Connexin 43 (Cx43) forms gap junction channels and hemichannels that allow the communication among osteocytes, osteoblasts, and osteoclasts. Cx43 carboxy-terminal (CT) domain regulates channel opening and intracellular signaling by acting as a scaffold for structural and signaling proteins. To determine the role of Cx43 CT domain in bone, mice in which one allele of full length Cx43 was replaced by a mutant lacking the CT domain (Cx43(ΔCT/fl)) were studied. Cx43(ΔCT/fl) mice exhibit lower cancellous bone volume but higher cortical thickness than Cx43(fl/fl) controls, indicating that the CT domain is involved in normal cancellous bone gain but opposes cortical bone acquisition. Further, Cx43(ΔCT) is able to exert the functions of full length osteocytic Cx43 on cortical bone geometry and mechanical properties, demonstrating that domains other than the CT are responsible for Cx43 function in cortical bone. In addition, parathyroid hormone (PTH) failed to increase endocortical bone formation or energy to failure, a mechanical property that indicates resistance to fracture, in cortical bone in Cx43(ΔCT) mice with or without osteocytic full length Cx43. On the other hand, bone mass and bone formation markers were increased by the hormone in all mouse models, regardless of whether full length or Cx43(ΔCT) were or not expressed. We conclude that Cx43 CT domain is involved in proper bone acquisition; and that Cx43 expression in osteocytes is dispensable for some but not all PTH anabolic actions

Critical animal and media studies: Expanding the understanding of oppression in communication research

Critical and communication studies have traditionally neglected the oppression conducted by humans towards other animals. However, our (mis)treatment of other animals is the result of public consent supported by a morally speciesist-anthropocentric system of values. Speciesism or anthroparchy, as much as any other mainstream ideologies, feeds the media and at the same time is perpetuated by them. The goal of this article is to remedy this neglect by introducing the subdiscipline of Critical Animal and Media Studies. Critical Animal and Media Studies takes inspiration both from critical animal studies – which is so far the most consolidated critical field of research in the social sciences addressing our exploitation of other animals – and from the normative-moral stance rooted in the cornerstones of traditional critical media studies. The authors argue that the Critical Animal and Media Studies approach is an unavoidable step forward for critical media and communication studies to engage with the expanded circle of concerns of contemporary ethical thinking

LOGISTICS IN CONTESTED ENVIRONMENTS

This report examines the transport and delivery of logistics in contested environments within the context of great-power competition (GPC). Across the Department of Defense (DOD), it is believed that GPC will strain our current supply lines beyond their capacity to maintain required warfighting capability. Current DOD efforts are underway to determine an appropriate range of platforms, platform quantities, and delivery tactics to meet the projected logistics demand in future conflicts. This report explores the effectiveness of various platforms and delivery methods through analysis in developed survivability, circulation, and network optimization models. Among other factors, platforms are discriminated by their radar cross-section (RCS), noise level, speed, cargo capacity, and self-defense capability. To maximize supply delivered and minimize the cost of losses, the results of this analysis indicate preference for utilization of well-defended convoys on supply routes where bulk supply is appropriate and smaller, and widely dispersed assets on shorter, more contested routes with less demand. Sensitivity analysis on these results indicates system survivability can be improved by applying RCS and noise-reduction measures to logistics assets.Director, Warfare Integration (OPNAV N9I)Major, Israel Defence ForcesCivilian, Singapore Technologies Engineering Ltd, SingaporeCommander, Republic of Singapore NavyCommander, United States NavyCaptain, Singapore ArmyLieutenant, United States NavyLieutenant, United States NavyMajor, Republic of Singapore Air ForceCaptain, United States Marine CorpsLieutenant, United States NavyLieutenant, United States NavyLieutenant, United States NavyLieutenant, United States NavyLieutenant, United States NavyCaptain, Singapore ArmyLieutenant Junior Grade, United States NavyCaptain, Singapore ArmyLieutenant Colonel, Republic of Singapore Air ForceApproved for public release. distribution is unlimite

Spatiotemporal Patterns and Risk Factors for Lead Exposure in Endangered California Condors during 15 Years of Reintroduction

Large-scale poisoning events are common to scavenging bird species that forage communally, many of which are in decline. To reduce the threat of poisoning and compensate for other persistent threats, management, including supplemental feeding, is ongoing for many reintroduced and endangered vulture populations. Through a longitudinal study of lead exposure in California condors (Gymnogyps californianus), we illustrate the conservation challenges inherent in reintroduction of an endangered species to the wild when pervasive threats have not been eliminated. We evaluated population-wide patterns in blood lead levels from 1997 to 2011 and assessed a broad range of putative demographic, behavioral, and environmental risk factors for elevated lead exposure among reintroduced California condors in California (United States). We also assessed the effectiveness of lead ammunition regulations within the condor’s range in California by comparing condor blood lead levels before and after implementation of the regulations. Lead exposure was a pervasive threat to California condors despite recent regulations limiting lead ammunition use. In addition, condor lead levels significantly increased as age and independence from intensive management increased, including increasing time spent away from managed release sites, and decreasing reliance on food provisions. Greater independence among an increasing number of reintroduced condors has therefore elevated the population’s risk of lead exposure and limited the effectiveness of lead reduction efforts to date. Our findings highlight the challenges of restoring endangered vulture populations as they mature and become less reliant on management actions necessary to compensate for persistent threats.Keywords: Gymnogyps californianus, Vulture, Scavenger, Ecotoxicology, Epidemiology, Wildlife diseaseKeywords: Gymnogyps californianus, Vulture, Scavenger, Ecotoxicology, Epidemiology, Wildlife diseas

Rare variant analyses validate known ALS genes in a multi-ethnic population and identifies ANTXR2 as a candidate in PLS

BackgroundAmyotrophic lateral sclerosis (ALS) is a neurodegenerative disease affecting over 300,000 people worldwide. It is characterized by the progressive decline of the nervous system that leads to the weakening of muscles which impacts physical function. Approximately, 15% of individuals diagnosed with ALS have a known genetic variant that contributes to their disease. As therapies that slow or prevent symptoms continue to develop, such as antisense oligonucleotides, it is important to discover novel genes that could be targets for treatment. Additionally, as cohorts continue to grow, performing analyses in ALS subtypes, such as primary lateral sclerosis (PLS), becomes possible due to an increase in power. These analyses could highlight novel pathways in disease manifestation.MethodsBuilding on our previous discoveries using rare variant association analyses, we conducted rare variant burden testing on a substantially larger multi-ethnic cohort of 6,970 ALS patients, 166 PLS patients, and 22,524 controls. We used intolerant domain percentiles based on sub-region Residual Variation Intolerance Score (subRVIS) that have been described previously in conjunction with gene based collapsing approaches to conduct burden testing to identify genes that associate with ALS and PLS.ResultsA gene based collapsing model showed significant associations with SOD1, TARDBP, and TBK1 (OR = 19.18, p = 3.67 × 10–39; OR = 4.73, p = 2 × 10–10; OR = 2.3, p = 7.49 × 10–9, respectively). These genes have been previously associated with ALS. Additionally, a significant novel control enriched gene, ALKBH3 (p = 4.88 × 10–7), was protective for ALS in this model. An intolerant domain-based collapsing model showed a significant improvement in identifying regions in TARDBP that associated with ALS (OR = 10.08, p = 3.62 × 10–16). Our PLS protein truncating variant collapsing analysis demonstrated significant case enrichment in ANTXR2 (p = 8.38 × 10–6).ConclusionsIn a large multi-ethnic cohort of 6,970 ALS patients, collapsing analyses validated known ALS genes and identified a novel potentially protective gene, ALKBH3. A first-ever analysis in 166 patients with PLS found a candidate association with loss-of-function mutations in ANTXR2

An international effort towards developing standards for best practices in analysis, interpretation and reporting of clinical genome sequencing results in the CLARITY Challenge

There is tremendous potential for genome sequencing to improve clinical diagnosis and care once it becomes routinely accessible, but this will require formalizing research methods into clinical best practices in the areas of sequence data generation, analysis, interpretation and reporting. The CLARITY Challenge was designed to spur convergence in methods for diagnosing genetic disease starting from clinical case history and genome sequencing data. DNA samples were obtained from three families with heritable genetic disorders and genomic sequence data were donated by sequencing platform vendors. The challenge was to analyze and interpret these data with the goals of identifying disease-causing variants and reporting the findings in a clinically useful format. Participating contestant groups were solicited broadly, and an independent panel of judges evaluated their performance. RESULTS: A total of 30 international groups were engaged. The entries reveal a general convergence of practices on most elements of the analysis and interpretation process. However, even given this commonality of approach, only two groups identified the consensus candidate variants in all disease cases, demonstrating a need for consistent fine-tuning of the generally accepted methods. There was greater diversity of the final clinical report content and in the patient consenting process, demonstrating that these areas require additional exploration and standardization. CONCLUSIONS: The CLARITY Challenge provides a comprehensive assessment of current practices for using genome sequencing to diagnose and report genetic diseases. There is remarkable convergence in bioinformatic techniques, but medical interpretation and reporting are areas that require further development by many groups

AI is a viable alternative to high throughput screening: a 318-target study

: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery