2,929 research outputs found
Current-Traditional Rhetoric and the Hodges Harbrace Handbook: A Study in the Disconnect Between Theory and Practice
In the 1980s and 1990s, current-traditional rhetoric (CTR) was a popular topic in rhetoric and composition scholarship as the field justified its move away from CTR in an attempt to offer more authentic and process-based forms of writing instruction. Since that time, however, scholarship on the topic has decreased, likely because scholarship has dismissed CTR as a viable composition pedagogy. Though CTR is no longer a popular topic in scholarship, it should still be addressed in scholarship because there are still writing instructors who utilize it to teach writing as a prescriptive, form-first endeavor that minimizes the role of audience and purpose.
This dissertation argues that CTR still exists, and as such, should receive more attention in composition scholarship. One of the reasons that CTR still exists is because the conditions that gave rise to it still exist, but most important here is that CTR still exists because it is perpetuated through textbooks, particularly the purported best-selling textbook of all time, the Hodges Harbrace Handbook. This dissertation traces the origins of the Hodges Harbrace Handbook as well as the history of John C. Hodges, the text’s initial author, as a means of illustrating the ways that a pedagogical theory, CTR, which has been dismissed in scholarship, continues to make its way into composition classrooms. This dissertation also discusses the problematic implications of the text’s continued use in college composition classrooms and proposes public pedagogy as one possible alternative to CTR because of its ability to reintroduce the components of writing that are removed in CTR
A microfluidic processor for gene expression profiling of single human embryonic stem cells
The gene expression of human embryonic stem cells (hESC) is a critical aspect for understanding the normal and pathological development of human cells and tissues. Current bulk gene expression assays rely on RNA extracted from cell and tissue samples with various degree of cellular heterogeneity. These cell population averaging data are difficult to interpret, especially for the purpose of understanding the regulatory relationship of genes in the earliest phases of development and differentiation of individual cells. Here, we report a microfluidic approach that can extract total mRNA from individual single-cells and synthesize cDNA on the same device with high mRNA-to-cDNA efficiency. This feature makes large-scale single-cell gene expression profiling possible. Using this microfluidic device, we measured the absolute numbers of mRNA molecules of three genes (B2M, Nodal and Fzd4) in a single hESC. Our results indicate that gene expression data measured from cDNA of a cell population is not a good representation of the expression levels in individual single cells. Within the G0/G1 phase pluripotent hESC population, some individual cells did not express all of the 3 interrogated genes in detectable levels. Consequently, the relative expression levels, which are broadly used in gene expression studies, are very different between measurements from population cDNA and single-cell cDNA. The results underscore the importance of discrete single-cell analysis, and the advantages of a microfluidic approach in stem cell gene expression studies
Impaired Competence for Pretense in Children with Autism: Exploring Potential Cognitive Predictors.
Lack of pretense in children with autism has been explained by a number of theoretical explanations, including impaired mentalising, impaired response inhibition, and weak central coherence. This study aimed to empirically test each of these theories. Children with autism (n=60) were significantly impaired relative to controls (n=65) when interpreting pretense, thereby supporting a competence deficit hypothesis. They also showed impaired mentalising and response inhibition, but superior local processing indicating weak central coherence. Regression analyses revealed that mentalising significantly and independently predicted pretense. The results are interpreted as supporting the impaired mentalising theory and evidence against competing theories invoking impaired response inhibition or a local processing bias. The results of this study have important implications for treatment and intervention
Within-trial cost and 1-year cost-effectiveness of the DiRECT/Counterweight-Plus weight-management programme to achieve remission of type 2 diabetes
No abstract available
The Diabetes Remission Clinical Trial (DiRECT): protocol for a cluster randomised trial
Background:
Despite improving evidence-based practice following clinical guidelines to optimise drug therapy, Type 2 diabetes (T2DM) still exerts a devastating toll from vascular complications and premature death. Biochemical remission of T2DM has been demonstrated with weight loss around 15kg following bariatric surgery and in several small studies of non-surgical energy-restriction treatments. The non-surgical Counterweight-Plus programme, running in Primary Care where obesity and T2DM are routinely managed, produces >15 kg weight loss in 33 % of all enrolled patients. The Diabetes UK-funded Counterpoint study suggested that this should be sufficient to reverse T2DM by removing ectopic fat in liver and pancreas, restoring first-phase insulin secretion.
The Diabetes Remission Clinical Trial (DiRECT) was designed to determine whether a structured, intensive, weight management programme, delivered in a routine Primary Care setting, is a viable treatment for achieving durable normoglycaemia. Other aims are to understand the mechanistic basis of remission and to identify psychological predictors of response.
Methods/Design:
Cluster-randomised design with GP practice as the unit of randomisation: 280 participants from around 30 practices in Scotland and England will be allocated either to continue usual guideline-based care or to add the Counterweight-Plus weight management programme, which includes primary care nurse or dietitian delivery of 12-20weeks low calorie diet replacement, food reintroduction, and long-term weight loss maintenance. Main inclusion criteria: men and women aged 20-65years, all ethnicities, T2DM 0-6years duration, BMI 27-45 kg/m2. Tyneside participants will undergo Magnetic Resonance (MR) studies of pancreatic and hepatic fat, and metabolic studies to determine mechanisms underlying T2DM remission. Co-primary endpoints: weight reduction ≥ 15 kg and HbA1c <48 mmol/mol at one year. Further follow-up at 2 years.
Discussion:
This study will establish whether a structured weight management programme, delivered in Primary Care by practice nurses or dietitians, is a viable treatment to achieve T2DM remission. Results, available from 2018 onwards, will inform future service strategy
Body size data collected non-invasively from drone images indicate a morphologically distinct Chilean blue whale (Blaenoptera musculus) taxon
© The Author(s), 2020. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Leslie, M. S., Perkins-Taylor, C. M., Durban, J. W., Moore, M. J., Miller, C. A., Chanarat, P., Bahamonde, P., Chiang, G., & Apprill, A. Body size data collected non-invasively from drone images indicate a morphologically distinct Chilean blue whale (Blaenoptera musculus) taxon. Endangered Species Research, 43, (2020): 291-304, https://doi.org/10.3354/esr01066.The blue whale Balaenoptera musculus (Linnaeus, 1758) was the target of intense commercial whaling in the 20th century, and current populations remain drastically below pre-whaling abundances. Reducing uncertainty in subspecific taxonomy would enable targeted conservation strategies for the recovery of unique intraspecific diversity. Currently, there are 2 named blue whale subspecies in the temperate to polar Southern Hemisphere: the Antarctic blue whale B. m. intermedia and the pygmy blue whale B. m. brevicauda. These subspecies have distinct morphologies, genetics, and acoustics. In 2019, the Society for Marine Mammalogy’s Committee on Taxonomy agreed that evidence supports a third (and presently unnamed) subspecies of Southern Hemisphere blue whale subspecies, the Chilean blue whale. Whaling data indicate that the Chilean blue whale is intermediate in body length between pygmy and Antarctic blue whales. We collected body size data from blue whales in the Gulfo Corcovado, Chile, during the austral summers of 2015 and 2017 using aerial photogrammetry from a remotely controlled drone to test the hypothesis that the Chilean blue whale is morphologically distinct from other Southern Hemisphere blue whale subspecies. We found the Chilean whale to be morphologically intermediate in both overall body length and relative tail length, thereby joining other diverse data in supporting the Chilean blue whale as a unique subspecific taxon. Additional photogrammetry studies of Antarctic, pygmy, and Chilean blue whales will help examine unique morphological variation within this species of conservation concern. To our knowledge, this is the first non-invasive small drone study to test a hypothesis for systematic biology.We are thankful to Foundation MERI (Melimoyu Ecosystem Research Institute) for logistical and funding support. Cruise support in 2017 was provided by the Dalio Foundation (now ‘OceanX’)
Redox linked flavin sites in extracellular decaheme proteins involved in microbe-mineral electron transfer
Extracellular microbe-mineral electron transfer is a major driving force for the oxidation of organic carbon in many subsurface environments. Extracellular multi-heme cytochromes of the Shewenella genus play a major role in this process but the mechanism of electron exchange at the interface between cytochrome and acceptor is widely debated. The 1.8 Å x-ray crystal structure of the decaheme MtrC revealed a highly conserved CX8C disulfide that, when substituted for AX8A, severely compromised the ability of S. oneidensis to grow under aerobic conditions. Reductive cleavage of the disulfide in the presence of flavin mononucleotide (FMN) resulted in the reversible formation of a stable flavocytochrome. Similar results were also observed with other decaheme cytochromes, OmcA, MtrF and UndA. The data suggest that these decaheme cytochromes can transition between highly reactive flavocytochromes or less reactive cytochromes, and that this transition is controlled by a redox active disulfide that responds to the presence of oxygen
Small molecule induced reactivation of mutant p53 in cancer cells
The p53 cancer mutant Y220C is an excellent paradigm for rescuing the function of conformationally unstable p53 mutants because it has a unique surface crevice that can be targeted by small-molecule stabilizers. Here, we have identified a compound, PK7088, which is active in vitro: PK7088 bound to the mutant with a dissociation constant of 140 μM and raised its melting temperature, and we have determined the binding mode of a close structural analogue by X-ray crystallography. We showed that PK7088 is biologically active in cancer cells carrying the Y220C mutant by a battery of tests. PK7088 increased the amount of folded mutant protein with wild-type conformation, as monitored by immunofluorescence, and restored its transcriptional functions. It induced p53-Y220C-dependent growth inhibition, cell-cycle arrest and apoptosis. Most notably, PK7088 increased the expression levels of p21 and the proapoptotic NOXA protein. PK7088 worked synergistically with Nutlin-3 on up-regulating p21 expression, whereas Nutlin-3 on its own had no effect, consistent with its mechanism of action. PK7088 also restored non-transcriptional apoptotic functions of p53 by triggering nuclear export of BAX to the mitochondria. We suggest a set of criteria for assigning activation of p53
Cladoceran birth and death rates estimates
I. Birth and death rates of natural cladoceran populations cannot be measured directly. Estimates of these population parameters must be calculated using methods that make assumptions about the form of population growth. These methods generally assume that the population has a stable age distribution.
2. To assess the effect of variable age distributions, we tested six egg ratio methods for estimating birth and death rates with data from thirty-seven laboratory populations of Daphnia pulicaria. The populations were grown under constant conditions, but the initial age distributions and egg ratios of the populations varied. Actual death rates were virtually zero, so the difference between the estimated and actual death rates measured the error in both birth and death rate estimates.
3. The results demonstrate that unstable population structures may produce large errors in the birth and death rates estimated by any of these methods. Among the methods tested, Taylor and Slatkin's formula and Paloheimo's formula were most reliable for the experimental data.
4. Further analyses of three of the methods were made using computer simulations of growth of age-structured populations with initially unstable age distributions. These analyses show that the time interval between sampling strongly influences the reliability of birth and death rate estimates. At a sampling interval of 2.5 days (equal to the duration of the egg stage), Paloheimo's formula was most accurate. At longer intervals (7.5–10 days), Taylor and Slatkin's formula which includes information on population structure was most accurate
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Leveraging population admixture to characterize the heritability of complex traits.
Despite recent progress on estimating the heritability explained by genotyped SNPs (h(2)g), a large gap between h(2)g and estimates of total narrow-sense heritability (h(2)) remains. Explanations for this gap include rare variants or upward bias in family-based estimates of h(2) due to shared environment or epistasis. We estimate h(2) from unrelated individuals in admixed populations by first estimating the heritability explained by local ancestry (h(2)γ). We show that h(2)γ = 2FSTCθ(1 - θ)h(2), where FSTC measures frequency differences between populations at causal loci and θ is the genome-wide ancestry proportion. Our approach is not susceptible to biases caused by epistasis or shared environment. We applied this approach to the analysis of 13 phenotypes in 21,497 African-American individuals from 3 cohorts. For height and body mass index (BMI), we obtained h(2) estimates of 0.55 ± 0.09 and 0.23 ± 0.06, respectively, which are larger than estimates of h(2)g in these and other data but smaller than family-based estimates of h(2)
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