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"Anderson, Collin"
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DP architects on Marina Bay : Evolution of a civic downtown
This book chronicles the history of DP Architects and its involvement in the creation of Singapore's Marina Bay over a period spanning 50 years. It discusses the relationship between land reclamation and the conception of architecture and public space in Singapore through projects that represent a diverse range of building types, including hotels, malls and offices, as well as cultural and performance spaces. Each project has a vital public component that contributes to the connectivity of Marina Bay and its success as the nation's civic core.
Book
Prefrontal allopregnanolone mediates the adverse effects of acute stress in a mouse model of tic pathophysiology
Ample evidence suggests that acute stress can worsen symptom severity in Tourette syndrome (TS); however, the neurobiological underpinnings of this phenomenon remain poorly understood. We previously showed that acute stress exacerbates tic-like and other TS-associated responses via the neurosteroid allopregnanolone (AP) in an animal model of repetitive behavioral pathology. To verify the relevance of this mechanism to tic pathophysiology, here we tested the effects of AP in a mouse model recapitulating the partial depletion of dorsolateral cholinergic interneurons (CINs) seen in post-mortem studies of TS. Mice underwent targeted depletion of striatal CINs during adolescence and were tested in young adulthood. Compared with controls, partially CIN-depleted male mice exhibited several TS-relevant abnormalities, including deficient prepulse inhibition (PPI) and increased grooming stereotypies after a 30-min session of spatial confinement - a mild acute stressor that increases AP levels in the prefrontal cortex (PFC). These effects were not seen in females. Systemic and intra-PFC AP administration dose-dependently worsened grooming stereotypies and PPI deficits in partially CIN-depleted males. Conversely, both AP synthesis inhibition and pharmacological antagonism reduced the effects of stress. These results further suggest that AP in the PFC mediates the adverse effects of stress on the severity of tics and other TS-related manifestations. Future studies will be necessary to confirm these mechanisms in patients and define the circuitry responsible for the effects of AP on tics.
Journal Article
Evolution of a retail streetscape : DP Architects on Orchard Road
Singapore's Orchard Road sits alongside New York's Fifth Avenue and Paris' Champs Elysees in the pantheon of prestigious retail districts. For more than 40 years, DP Architects has contributed to the development of Orchard Road's architectural typography, the regionalism of which is flavoured with a uniqueness born of inventiveness and an accommodation of contextual forces. 'The Orchard Road Experience' is much more than simply a lush visual and textual narrative showcasing DP Architects' extensive contribution to the character, growth and personality of the famous Singapore shopping and entertainment precinct. It also explores the concept of retail architectural typology generally, provides a brief contextual history of Singapore from British colonisation onwards, outlines the development and evolution of Orchard Road in particular, and explores some of the world's other famous shopping streets.
Book
Telomere Length Is a Determinant of Emphysema Susceptibility
Germline mutations in the enzyme telomerase cause telomere shortening, and have their most common clinical manifestation in age-related lung disease that manifests as idiopathic pulmonary fibrosis. Short telomeres are also a unique heritable trait that is acquired with age.
We sought to understand the mechanisms by which telomerase deficiency contributes to lung disease.
We studied telomerase null mice with short telomeres.
Although they have no baseline histologic defects, when mice with short telomeres are exposed to chronic cigarette smoke, in contrast with controls, they develop emphysematous air space enlargement. The emphysema susceptibility did not depend on circulating cell genotype, because mice with short telomeres developed emphysema even when transplanted with wild-type bone marrow. In lung epithelium, cigarette smoke exposure caused additive DNA damage to telomere dysfunction, which limited their proliferative recovery, and coincided with a failure to down-regulate p21, a mediator of cellular senescence, and we show here, a determinant of alveolar epithelial cell cycle progression. We also report early onset of emphysema, in addition to pulmonary fibrosis, in a family with a germline deletion in the Box H domain of the RNA component of telomerase.
Our data indicate that short telomeres lower the threshold of cigarette smoke-induced damage, and implicate telomere length as a genetic susceptibility factor in emphysema, potentially contributing to its age-related onset in humans.
Journal Article
Ancestral Mutation in Telomerase Causes Defects in Repeat Addition Processivity and Manifests As Familial Pulmonary Fibrosis
The telomerase reverse transcriptase synthesizes new telomeres onto chromosome ends by copying from a short template within its integral RNA component. During telomere synthesis, telomerase adds multiple short DNA repeats successively, a property known as repeat addition processivity. However, the consequences of defects in processivity on telomere length maintenance are not fully known. Germline mutations in telomerase cause haploinsufficiency in syndromes of telomere shortening, which most commonly manifest in the age-related disease idiopathic pulmonary fibrosis. We identified two pulmonary fibrosis families that share two non-synonymous substitutions in the catalytic domain of the telomerase reverse transcriptase gene hTERT: V791I and V867M. The two variants fell on the same hTERT allele and were associated with telomere shortening. Genealogy suggested that the pedigrees shared a single ancestor from the nineteenth century, and genetic studies confirmed the two families had a common founder. Functional studies indicated that, although the double mutant did not dramatically affect first repeat addition, hTERT V791I-V867M showed severe defects in telomere repeat addition processivity in vitro. Our data identify an ancestral mutation in telomerase with a novel loss-of-function mechanism. They indicate that telomere repeat addition processivity is a critical determinant of telomere length and telomere-mediated disease.
Journal Article
Suitability of Data-Collection Methods, Tools, and Metrics for Evaluating Market Food Environments in Low- and Middle-Income Countries
Globalization is transforming food environments in low- and middle-income countries (LMICs) with implications for diets and nutrition. However, most food-environment assessments were developed for use in high-income countries. We evaluated the suitability of 113 data-collection assessments (i.e., methods, tools, and metrics) for eight dimensions of informal and formal market food environments for diverse contexts of LMICs. We used a scoring exercise and a survey of experts (n = 27). According to the scoring exercise, 10 assessments (8 methods, 1 tool, and 1 metric) were suitable without modification for informal markets. Suitability for formal markets was markedly higher, with 41 assessments (21 methods, 14 tools, and 6 metrics) found suitable without modification. Experts considered availability, accessibility, price, and affordability the most important dimensions of market food environments to evaluate in LMICs. Market-basket analysis and vendor audits (which include inventories) were ranked as the most suitable methods to assess multiple dimensions of market food environments, including availability, price, affordability, vendor and product characteristics, marketing, and regulation. Gaps in relevant assessments were found for convenience and desirability. Results demonstrate the need for the development, adaptation, and validation of assessments relevant for informal markets in a diverse range of LMIC contexts to support diets, nutrition, and health globally.
Journal Article
Retrospective single center comparison of transcatheter aortic valve replacement cost per minute using general anesthesia versus sedation
•Mode of anesthesia delivery (sedation vs. general) impacts TAVR time but not cost.•Overall cost per minute with sedation is not reduced due to fixed procedural costs.•Fixed costs include wages, benefits, and supplies; TAVR valve is most expensive.
Journal Article
Subthalamic deep brain stimulation reduces pathological information transmission to the thalamus in a rat model of parkinsonism
The degeneration of dopaminergic neurons in the substantia nigra pars compacta leads to parkinsonian motor symptoms via changes in electrophysiological activity throughout the basal ganglia. High-frequency deep brain stimulation (DBS) partially treats these symptoms, but the mechanisms are unclear. We hypothesize that motor symptoms of Parkinson's disease (PD) are associated with increased information transmission from basal ganglia output neurons to motor thalamus input neurons and that therapeutic DBS of the subthalamic nucleus (STN) treats these symptoms by reducing this extraneous information transmission. We tested these hypotheses in a unilateral, 6-hydroxydopamine-lesioned rodent model of hemiparkinsonism. Information transfer between basal ganglia output neurons and motor thalamus input neurons increased in both the orthodromic and antidromic directions with hemiparkinsonian (hPD) onset, and these changes were reversed by behaviorally therapeutic STN-DBS. Omnidirectional information increases in the parkinsonian state underscore the detrimental nature of that pathological information and suggest a loss of information channel independence. Therapeutic STN-DBS reduced that pathological information, suggesting an effective increase in the number of independent information channels. We interpret these data with a model in which pathological information and fewer information channels diminishes the scope of possible motor activities, driving parkinsonian symptoms. In this model, STN-DBS restores information-channel independence by eliminating or masking the parkinsonism-associated information, and thus enlarges the scope of possible motor activities, alleviating parkinsonian symptoms.
Journal Article
Current Opinions and Consensus for Studying Tremor in Animal Models
Tremor is the most common movement disorder; however, we are just beginning to understand the brain circuitry that generates tremor. Various neuroimaging, neuropathological, and physiological studies in human tremor disorders have been performed to further our knowledge of tremor. But, the causal relationship between these observations and tremor is usually difficult to establish and detailed mechanisms are not sufficiently studied. To overcome these obstacles, animal models can provide an important means to look into human tremor disorders. In this manuscript, we will discuss the use of different species of animals (mice, rats, fruit flies, pigs, and monkeys) to model human tremor disorders. Several ways to manipulate the brain circuitry and physiology in these animal models (pharmacology, genetics, and lesioning) will also be discussed. Finally, we will discuss how these animal models can help us to gain knowledge of the pathophysiology of human tremor disorders, which could serve as a platform towards developing novel therapies for tremor.
Journal Article
Stability of Fentanyl Citrate, Hydromorphone Hydrochloride, Ketamine Hydrochloride, Midazolam, Morphine Sulfate, and Pentobarbital Sodium in Polypropylene Syringes
Purpose: Determine the stability of fentanyl 10 mcg/mL in 0.9% sodium chloride, fentanyl 10 mcg/mL in 5% dextrose, fentanyl 50 mcg/mL, hydromorphone 100 mcg/mL in 0.9% sodium chloride, ketamine 10 mg/mL, midazolam 0.4 mg/mL in 5% dextrose, midazolam 5 mg/mL, morphine 1 mg/mL in 0.9% sodium chloride, morphine 1 mg/mL in 5% dextrose, and pentobarbital 50 mg/mL when stored as single drug entities at room temperature in polypropylene syringes. Methods: Four 5 mL samples of each drug and concentration were prepared in 10 mL polypropylene syringes. The samples were stored at ambient room temperature in a locked cabinet. Triplicate determinations of drug concentration for each sample were performed initially, on day 50 or 51, and on day 100 using high-performance liquid chromatography with diode-array detection. Results: With the exception of the hydromorphone 100 mcg/mL dilution, all compounds were found to contain greater than 95% of their initial concentration remaining at 100 days. Each sample remained clear and colorless when visually inspected.
Journal Article