An Exploration of Public Misconceptions of Municipal Water Fluoridation Relating to Oral and Public Health

Municipal water fluoridation began in 1945, and in the past 70 years, it appears to have decreased the rate of dental caries nationwide. Despite being deemed one of the top ten innovations of the 20th century, there continues to be misconceptions with this controversial practice. The intent of this thesis is to address some of the misconceptions with water fluoridation, and what possible solutions could be provided to alleviate the concerns. This was accomplished through a literature review of current research articles. Two main topics were explored: the public health and oral health concerns and how they contribute to the controversy. Results from the literature show that there was an increasing campaign from anti-fluoridators that use misleading information to advocate for ceasing water fluoridation. There was also a common concern about fluoridated water causing dental fluorosis. Furthermore, there was a trend with the lack of education and knowledge about water fluoridation, predominately in rural and low-income communities. Overall, it was reasoned that the best way to reduce the misconceptions of water fluoridation is to increase educational opportunities through medical professionals creating inter-department relationships and redirecting various government programs to target different populations

Influences of Friends and Friendships on Adjustment to Junior High School

To explore influences of friends and friendships on adjustment to junior high school, 101 students were interviewed about their friendships in the spring of sixth grade and again in the fall and spring of seventh grade. Adjustment was judged from self-reports, peer nominations, teacher ratings, and school records. Sociability and leadership increased across the transition if students had high-quality friendships in 6th grade that were mostly stable across the transition. Behavior problems increased if students had stable friendships with sixth-grade friends high in behavioral problems. Sensitivity-isolation of students with sensitive-isolated friends increased across the transition unless they had high-quality, stable friendships. Separate and interactive effects of friendships and friends\u27 characteristics were discussed

The semantic effects of verb raising and its consequences in second language grammars

This article considers whether highly proficient second language speakers of English can distinguish meaning contrasts associated with constructions where there is a raising be, and constructions where there is a non-raising thematic verb, as illustrated in the difference between (1a) and (1b): 1a. Kim is reading a novel (`event-in-progress/existential ? interpretation

Testing and Failure Mechanisms of Ice Phase Change Material Heat Exchangers

Phase change materials (PCM) may be useful for thermal control systems that involve cyclical heat loads or cyclical thermal environments such as Low Earth Orbit (LEO) and Low Lunar Orbit (LLO). Thermal energy can be stored in the PCM during peak heat loads or in adverse thermal environments. The stored thermal energy can then be released later during minimum heat loads or in more favorable thermal environments. One advantage that PCM s have over evaporators in this scenario is that they do not use a consumable. The use of water as a PCM rather than the more traditional paraffin wax has the potential for significant mass reduction since the latent heat of formation of water is approximately 70% greater than that of wax. One of the potential drawbacks of using ice as a PCM is its potential to rupture its container as water expands upon freezing. In order to develop a space qualified ice PCM heat exchanger, failure mechanisms must first be understood. Therefore, a methodical experimental investigation has been undertaken to demonstrate and document specific failure mechanisms due to ice expansion in the PCM. A number of ice PCM heat exchangers were fabricated and tested. Additionally, methods for controlling void location in order to reduce the risk of damage due to ice expansion were investigated. This paper presents the results of testing that occurred from March through September of 2010 and builds on testing that occurred during the previous year

The small molecule Mek1/2 inhibitor U0126 disrupts the chordamesoderm to notochord transition in zebrafish

<p>Abstract</p> <p>Background</p> <p>Key molecules involved in notochord differentiation and function have been identified through genetic analysis in zebrafish and mice, but MEK1 and 2 have so far not been implicated in this process due to early lethality (<it>Mek1-/-</it>) and functional redundancy (<it>Mek2-/-</it>) in the knockout animals.</p> <p>Results</p> <p>Here, we reveal a potential role for Mek1/2 during notochord development by using the small molecule Mek1/2 inhibitor U0126 which blocks phosphorylation of the Mek1/2 target gene Erk1/2 <it>in vivo</it>. Applying the inhibitor from early gastrulation until the 18-somite stage produces a specific and consistent phenotype with lack of dark pigmentation, shorter tail and an abnormal, undulated notochord. Using morphological analysis, in situ hybridization, immunhistochemistry, TUNEL staining and electron microscopy, we demonstrate that in treated embryos the chordamesoderm to notochord transition is disrupted and identify disorganization in the medial layer of the perinotochordal basement mebrane as the probable cause of the undulations and bulges in the notochord. We also examined and excluded FGF as the upstream signal during this process.</p> <p>Conclusion</p> <p>Using the small chemical U0126, we have established a novel link between MAPK-signaling and notochord differentiation. Our phenotypic analysis suggests a potential connection between the MAPK-pathway, the COPI-mediated intracellular transport and/or the copper-dependent posttranslational regulatory processes during notochord differentiation.</p

NRF2 Mediates Therapeutic Resistance to Chemoradiation in Colorectal Cancer through a Metabolic Switch

Radiation resistance is a significant clinical problem in rectal cancer treatment, the mechanisms of which are poorly understood. NRF2 signalling is known to contribute to chemo/radioresistance in some cancers, but its role in therapeutic resistance in colorectal cancer (CRC) is unexplored. Using siRNA and CRiSPR/Cas9 isogenic CRC cell lines, we investigated the effect of the knockdown and upregulation of the NRF2 pathway on chemo-radiosensitivity. Poly (A) enriched RNA sequencing and geneset enrichment analysis (GSEA) were carried out on both sensitive and resistant cell models for mechanistic insights. Finally, a cohort of rectal patient samples was profiled to understand the clinical relevance of NRF2 signalling. Radioresistant cell lines were significantly radiosensitised by siRNA knockdown (SW1463, SER10 1.22, ANOVA p < 0.0001; HT55, SER10 1.17, ANOVA p < 0.01), but not the (already) radiosensitive HCT116. The constitutive activation of NRF2 via a CRISPR Cas9 NFE2L2 mutation, E79K, induced radioresistance in HCT116 (SER10 0.71, ANOVA, p < 0.0001). GSEA demonstrated significant opposing metabolic dependencies in NRF2 signalling, specifically, the downregulation of amino acid and protein synthesis with low levels of NRF2 and upregulation with over expression. In a clinical cohort of 127 rectal patients, using a validated mRNA signature, higher baseline NRF2 signalling was associated with incomplete responses to radiation higher final neoadjuvant rectal (NAR) score (OR 1.34, 95% C.I. 1.01–1.80, LRT p-value = 0.023), where high NAR indicates poor radiation response and poor long-term prognosis. This is the first demonstration of NRF2-mediated radiation resistance in colorectal cancer. NRF2 appears to regulate crucial metabolic pathways, which could be exploited for therapeutic interventions

Systematic human/zebrafish comparative identification of cis-regulatory activity around vertebrate developmental transcription factor genes

AbstractPan-vertebrate developmental cis-regulatory elements are discernible as highly conserved noncoding elements (HCNEs) and are often dispersed over large areas around the pleiotropic genes whose expression they control. On the loci of two developmental transcription factor genes, SOX3 and PAX6, we demonstrate that HCNEs conserved between human and zebrafish can be systematically and reliably tested for their regulatory function in multiple stable transgenes in zebrafish, and their genomic reach estimated with confidence using synteny conservation and HCNE density along these loci. HCNEs of both human and zebrafish function as specific developmental enhancers in zebrafish. We show that human HCNEs result in expression patterns in zebrafish equivalent to those in mouse, establishing zebrafish as a suitable model for large-scale testing of human developmental enhancers. Orthologous human and zebrafish enhancers underwent functional evolution within their sequence and often directed related but non-identical expression patterns. Despite an evolutionary distance of 450 million years, one pax6 HCNE drove expression in identical areas when comparing zebrafish vs. human HCNEs. HCNEs from the same area often drive overlapping patterns, suggesting that multiple regulatory inputs are required to achieve robust and precise complex expression patterns exhibited by developmental genes

Testing asteroseismology with Gaia DR2: Hierarchical models of the Red Clump

Asteroseismology provides fundamental stellar parameters independent of distance, but subject to systematics under calibration. Gaia DR2 has provided parallaxes for a billion stars, which are offset by a parallax zero-point. Red Clump (RC) stars have a narrow spread in luminosity, thus functioning as standard candles to calibrate these systematics. This work measures how the magnitude and spread of the RC in the Kepler field are affected by changes to temperature and scaling relations for seismology, and changes to the parallax zero-point for Gaia. We use a sample of 5576 RC stars classified through asteroseismology. We apply hierarchical Bayesian latent variable models, finding the population level properties of the RC with seismology, and use those as priors on Gaia parallaxes to find the parallax zero-point offset. We then find the position of the RC using published values for the zero-point. We find a seismic temperature insensitive spread of the RC of ~0.03 mag in the 2MASS K band and a larger and slightly temperature-dependent spread of ~0.13 mag in the Gaia G band. This intrinsic dispersion in the K band provides a distance precision of ~1% for RC stars. Using Gaia data alone, we find a mean zero-point of -41 $\pm$ 10 $\mu$as. This offset yields RC absolute magnitudes of -1.634 $\pm$ 0.018 in K and 0.546 $\pm$ 0.016 in G. Obtaining these same values through seismology would require a global temperature shift of ~-70 K, which is compatible with known systematics in spectroscopy.Comment: Accepted for publication in MNRA

Estradiol effects on the dopamine transporter – protein levels, subcellular location, and function

BACKGROUND: The effects of estrogens on dopamine (DA) transport may have important implications for the increased incidence of neurological disorders in women during life stages when hormonal fluctuations are prevalent, e.g. during menarche, reproductive cycling, pregnancy, and peri-menopause. RESULTS: The activity of the DA transporter (DAT) was measured by the specific uptake of (3)H-DA. We found that low concentrations (10(-14 )to 10(-8 )M) of 17β-estradiol (E(2)) inhibit uptake via the DAT in PC12 cells over 30 minutes, with significant inhibition taking place due to E(2 )exposure during only the last five minutes of the uptake period. Such rapid action suggests a non-genomic, membrane-initiated estrogenic response mechanism. DAT and estrogen receptor-α (ERα) were elevated in cell extracts by a 20 ng/ml 2 day NGFβ treatment, while ERβ was not. DAT, ERα and ERβ were also detectable on the plasma membrane of unpermeabilized cells by immunocytochemical staining and by a fixed cell, quantitative antibody (Ab)-based plate assay. In addition, PC12 cells contained RNA coding for the alternative membrane ER GPR30; therefore, all 3 ER subtypes are candidates for mediating the rapid nongenomic actions of E(2). At cell densities above 15,000 cells per well, the E(2)-induced inhibition of transport was reversed. Uptake activity oscillated with time after a 10 nM E(2 )treatment; in a slower room temperature assay, inhibition peaked at 9 min, while uptake activity increased at 3 and 20–30 min. Using an Ab recognizing the second extracellular loop of DAT (accessible only on the outside of unpermeabilized cells), our immunoassay measured membrane vs. intracellular/nonvesicular DAT; both were found to decline over a 5–60 min E(2 )treatment, though immunoblot analyses demonstrated no total cellular loss of protein. CONCLUSION: Our results suggest that physiological levels of E(2 )may act to sequester DAT in intracellular compartments where the transporter's second extramembrane loop is inaccessible (inside vesicles) and that rapid estrogenic actions on this differentiated neuronal cell type may be regulated via membrane ERs of several types

Patient needs in advanced Renal Cell Carcinoma: What are patients’ priorities and how well are we meeting them?

Treatment options and duration of therapy for patients with metastatic renal cell carcinoma (mRCC) have increased. Many patients now spend in excess of 2 years on active therapy. These patients’ needs, and the ability of health services to respond to them, are poorly understood. Ten patients living with mRCC for more than 2 years and treated with at least one targeted agent were selected at random from three hospitals in the United Kingdom (UK). One interviewer who was not involved in their care conducted in-depth interviews. Interview transcripts were analysed using Interpretative Phenomenological Analysis (IPA) to identify issues of greatest importance to patients, and to understand how well patients felt their needs were being addressed. Perceived delay in initial diagnosis was a major theme. Being told the truth about treatment side effects upfront was important, but was often at odds with perceived delivery. ‘Dealing with side effects’, understanding dose and its effects and not letting ‘negative thoughts get in’ were highlighted as important, but were highly personal to patients and areas where patients struggled. Concordance was observed with delivery of ‘a clear next step’ for treatment, timely access to drugs and guidance on a drug ‘holiday’. Patient experience of mRCC and its treatment requires a tailored approach. This research suggests there are key opportunities for service improvement and improved communication throughout the pathway to better meet the needs of patients, including non-clinical support to build personal resilience