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Search Results: 1 - 10 of 158389 matches for " William B. Hamilton "
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ERK2 Suppresses Self-Renewal Capacity of Embryonic Stem Cells, but Is Not Required for Multi-Lineage Commitment
William B. Hamilton, Keisuke Kaji, Tilo Kunath
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0060907
Abstract: Activation of the FGF-ERK pathway is necessary for na?ve mouse embryonic stem (ES) cells to exit self-renewal and commit to early differentiated lineages. Here we show that genetic ablation of Erk2, the predominant ERK isozyme expressed in ES cells, results in hyper-phosphorylation of ERK1, but an overall decrease in total ERK activity as judged by substrate phosphorylation and immediate-early gene (IEG) induction. Normal induction of this subset of canonical ERK targets, as well as p90RSK phosphorylation, was rescued by transgenic expression of either ERK1 or ERK2 indicating a degree of functional redundancy. In contrast to previously published work, Erk2-null ES cells exhibited no detectable defect in lineage specification to any of the three germ layers when induced to differentiate in either embryoid bodies or in defined neural induction conditions. However, under self-renewing conditions Erk2-null ES cells express increased levels of the pluripotency-associated transcripts, Nanog and Tbx3, a decrease in Nanog-GFP heterogeneity, and exhibit enhanced self-renewal in colony forming assays. Transgenic add-back of ERK2 is capable of restoring normal pluripotent gene expression and self-renewal capacity. We show that ERK2 contributes to the destabilization of ES cell self-renewal by reducing expression of pluripotency genes, such as Nanog, but is not specifically required for the early stages of germ layer specification.
Design, assembly, and validation of a nose-only inhalation exposure system for studies of aerosolized viable influenza H5N1 virus in ferrets
Richard S Tuttle, William A Sosna, Deirdre E Daniels, Sara B Hamilton, John A Lednicky
Virology Journal , 2010, DOI: 10.1186/1743-422x-7-135
Abstract: An aerosol generation and delivery system, referred to as a Nose-Only Bioaerosol Exposure System (NBIES), was assembled and function tested. The NBIES passed all safety tests, met expected engineering parameters, required relatively small quantities of material to obtain the desired aerosol concentrations of influenza virus, and delivered doses with high-efficacy. Ferrets withstood a mock exposure trial without signs of stress.The NBIES delivers doses of aerosolized influenza viruses with high efficacy, and uses less starting material than other similar designs. Influenza H5N1 and H3N2 viruses remain stable under the conditions used for aerosol generation and sample collection. The NBIES is qualified for studies of aerosolized H5N1 virus.Human infections caused by highly pathogenic avian influenza H5N1 viruses (H5N1) that arose from 2003-onwards have been rare (495 cases confirmed through April 21, 2010) but have a fatality rate of about 59% [1]. There is limited knowledge about the potential routes and determinants required for H5N1 transmission to and between humans. Human-to-human transmissions have rarely been reported, and have been limited, inefficient and un-sustained. In ferret transmission models, H5N1 are inconsistent in transmission by direct or indirect contact exposure, but direct intranasal exposure causes morbidity and sometimes, mortality (2, 3, and J. Lednicky, unpublished). In contrast, the 1918 pandemic influenza virus was easily transmissible human-to-human, and caused the deaths of between 20 - 40 million people worldwide for a lethality rate of 2.5%. Whereas the differences in transmissibility and lethality between the two viruses are not fully understood, performing well-controlled inhalation exposure studies of aerosolized viable H5N1 in appropriate animal models may improve our understanding of factors responsible for -the acquisition of H5N1 infections by humans and the virulence/lethality relative to route of transmission.Four modes are mo
Ferrets develop fatal influenza after inhaling small particle aerosols of highly pathogenic avian influenza virus A/Vietnam/1203/2004 (H5N1)
John A Lednicky, Sara B Hamilton, Richard S Tuttle, William A Sosna, Deirdre E Daniels, David E Swayne
Virology Journal , 2010, DOI: 10.1186/1743-422x-7-231
Abstract: Ferrets were successfully infected through intranasal instillation or through inhalation of small particle aerosols with four different doses of Influenza virus A/Vietnam/1203/2004 (H5N1). The animals developed severe influenza encephalomyelitis following intranasal or inhalation exposure to 101, 102, 103, or 104 infectious virus particles per ferret.Aerosolized Influenza virus A/Vietnam/1203/2004 (H5N1) is highly infectious and lethal in ferrets. Clinical signs appeared earlier in animals infected through inhalation of aerosolized virus compared to those infected through intranasal instillation.Human infections caused by H5N1 highly pathogenic avian influenza viruses (H5N1) that arose from 2003-onwards have been rare as evident by only 500 cases confirmed through 5 July, 2010. However, H5N1 have a fatality rate of about 59% [1]. In ferret transmission models, the H5N1 viruses were inconsistent in transmission by direct or indirect contact exposure including respiratory droplets, but direct intranasal exposure caused morbidity and sometimes, mortality [2,3]. In contrast, the 1918 pandemic influenza virus was easily transmissible, especially human-to-human, and caused the deaths of between 20 - 40 million people worldwide for a lethality rate of 2.5%, and experimental studies demonstrated efficient transmission ferret-to-ferret by respiratory droplets [4]. The differences in transmissibility and lethality between the two viruses is not fully understood, but the use of aerosol challenge may improve our understanding of factors responsible for transmission and lethality of the H5N1 viruses.There is limited knowledge about the potential routes and determinants required for H5N1 influenza virus transmission to and between humans, and it is not clear whether humans can be infected through inhalation of aerosolized contemporary H5N1 virus particles. Receptor distribution in the human airway is proposed to restrict efficient inter-human transmission of H5N1 influenza virus
Pathways to the diagnosis of lung cancer in the UK: a cohort study
Jacqueline Barrett, William Hamilton
BMC Family Practice , 2008, DOI: 10.1186/1471-2296-9-31
Abstract: Three main routes to diagnosis emerged. The first was the expected route of outpatient referral; 150 (61% of the cohort) of patients took this route, although only 110 (45% of the whole cohort, 73% of those referred to outpatients) were referred to a respiratory department. 56 (23%) were admitted as an emergency, having previously described a lung cancer symptom to their doctor. 26 patients (11%) had no symptom of lung cancer reported before their diagnosis. The interval from first symptom to referral was similar across the different pathways. However, the referral to diagnosis interval was longer in patients misdirected to other outpatient departments (66 days, interquartile range 37,110) than those sent to respiratory clinics (29 days, 17,61) or admitted as an emergency (16 days 8,40); p < 0.001.Only a minority of lung cancer patients follow the traditional route to diagnosis. Clinical and research efforts need to consider the alternative routes if they are to maximise their impact on speed of diagnosis.Over 37,000 new lung cancers are diagnosed each year in the UK [1]. Mortality is very high, with lung cancer the leading cause of cancer deaths in the UK [1]. The poor survival reflects the intrinsically aggressive nature of the tumour, with the shortest doubling time of the common cancers, plus the fact that symptoms occur relatively late in the growth of the cancer [2]. Many patients also delay presenting their symptoms to their doctor, and the duration of symptoms is now recognised to be longer than previously thought [3,4]. Thus few patients are diagnosed at a stage when they could be offered curative surgery [5]. Furthermore, no screening test has been found to be effective, and none is near to implementation, though trials are in progress using spiral CT [5]. Most lung cancers present with symptoms, and in the UK, most of these patients present initially to their general practitioner (GP) [6].Unlike for most other common cancers, there exists a primary care i
Roadless Wilderness Area Determines Forest Elephant Movements in the Congo Basin
Stephen Blake, Sharon L. Deem, Samantha Strindberg, Fiona Maisels, Ludovic Momont, Inogwabini-Bila Isia, Iain Douglas-Hamilton, William B. Karesh, Michael D. Kock
PLOS ONE , 2008, DOI: 10.1371/journal.pone.0003546
Abstract: A dramatic expansion of road building is underway in the Congo Basin fuelled by private enterprise, international aid, and government aspirations. Among the great wilderness areas on earth, the Congo Basin is outstanding for its high biodiversity, particularly mobile megafauna including forest elephants (Loxodonta africana cyclotis). The abundance of many mammal species in the Basin increases with distance from roads due to hunting pressure, but the impacts of road proliferation on the movements of individuals are unknown. We investigated the ranging behaviour of forest elephants in relation to roads and roadless wilderness by fitting GPS telemetry collars onto a sample of 28 forest elephants living in six priority conservation areas. We show that the size of roadless wilderness is a strong determinant of home range size in this species. Though our study sites included the largest wilderness areas in central African forests, none of 4 home range metrics we calculated, including core area, tended toward an asymptote with increasing wilderness size, suggesting that uninhibited ranging in forest elephants no longer exists. Furthermore we show that roads outside protected areas which are not protected from hunting are a formidable barrier to movement while roads inside protected areas are not. Only 1 elephant from our sample crossed an unprotected road. During crossings her mean speed increased 14-fold compared to normal movements. Forest elephants are increasingly confined and constrained by roads across the Congo Basin which is reducing effective habitat availability and isolating populations, significantly threatening long term conservation efforts. If the current road development trajectory continues, forest wildernesses and the forest elephants they contain will collapse.
Gas-permeable ethylene bags for the small scale cultivation of highly pathogenic avian influenza H5N1 and other viruses in embryonated chicken eggs
Sara B Hamilton, Deirdre E Daniels, William A Sosna, Eric R Jeppesen, Julie M Owells, Micah D Halpern, Kimberly S McCurdy, Jonathan O Rayner, John A Lednicky
Virology Journal , 2010, DOI: 10.1186/1743-422x-7-23
Abstract: Virus yields acceptable for many applications were attained when influenza-, alpha-, flavi-, canine distemper-, and mousepox viruses were propagated in ECE sealed within ethylene breather bags.For many small-scale applications, ethylene breather bags can be used to encase ECE inoculated with various viruses.Embryonated (embryonating) chicken eggs (ECE) have long been used for isolating or propagating influenza and other viruses and certain bacteria such as Rickettsia [1-5]. Alpha-, corona-, flavi-, paramyxo-, and poxviruses are among the non-influenza viruses sometimes grown in ECE. For small-scale work with pathogens that must be worked with in BSL3 facilities, inoculated ECE are sometimes housed in small egg incubators kept within a BSC [such a practice is not practical for medium-to-large diagnostic operations, wherein ECE are placed in incubators within a bioBubble (Ft. Collins, CO) or similar barrier and containment enclosure]. Since ECE are fragile, accidental egg breakage is possible. Furthermore, diagnostic specimens inoculated into ECE may contain contaminating flora that form enough gas to break the egg shell. We sought a simple method to contain spillage from a broken ECE inoculated with dangerous pathogens, and explored the feasibility of using ethylene breather bags for that purpose. Ethylene breather bags are permeable to oxygen and carbon dioxide but retain water, and are used in the aquarium industry to transport live fish. Chicken embryo survival was examined and the yield of various influenza and other viruses in bagged eggs was determined.No differences were detected in the survival of chicken embryos in bagged vs non-bagged 7 - 12 day old ECE after five days of incubation without rotation as performed for virus-inoculated ECE. Noteworthy, especially during summer months, up to 20% attrition (death of non-inoculated ECE) occurred with some batches, regardless of whether the ECE were bagged or not bagged. Since the ECE are checked and culled if dea
Linear frictional forces cause orbits to neither circularize nor precess
B. Hamilton,M. Crescimanno
Physics , 2007, DOI: 10.1088/1751-8113/41/23/235205
Abstract: For the undamped Kepler potential the lack of precession has historically been understood in terms of the Runge-Lenz symmetry. For the damped Kepler problem this result may be understood in terms of the generalization of Poisson structure to damped systems suggested recently by Tarasov[1]. In this generalized algebraic structure the orbit-averaged Runge-Lenz vector remains a constant in the linearly damped Kepler problem to leading order in the damping coe
Recent Results in Semileptonic B Decays With BaBar
B. K. Hamilton
Statistics , 2011,
Abstract: In this note, recent results of studies of semileptonic B meson decays from \babar\ are discussed and preliminary results given. In particular, a recent measurement of $\mathcal{B}(B \to D^{(*)}\tau \nu)$ and the ratio $\mathcal{B}(B \to D^{(*)}\tau \nu)/\mathcal{B}(B \to D^{(*)}\ell \nu)$ is presented. For the $D^*$ mode, a branching fraction of $1.79\pm0.13\stat\pm0.17\syst$ is found, with a ratio of $0.325\pm0.023\stat\pm0.027\syst$. For the $D$ mode, the results are $1.04\pm0.12\stat\pm0.14\syst$ and $0.456\pm0.053\stat\pm0.056\syst$, respectively. In addition, a study of $B_s$ production and semileptonic decays using data collected in a center-of-mass energy region above the \Y4S resonance is discussed. The semileptonic branching fraction $\mathcal{B}(B_s \to \ell \nu X)$ is measured to be $9.9{}^{+2.6}_{-2.1}\stat{}^{+1.3}_{-2.0}\syst$.
Creating Student Engagement? HMM: Teaching and Learning with Humor, Music, and Movement  [PDF]
William B Strean
Creative Education (CE) , 2011, DOI: 10.4236/ce.2011.23026
Abstract: With growing concerns about student engagement, the theme of creative teaching and learning provides an excellent catalyst to consider methods that enhance students’ classroom experiences. Good teaching is akin to weaving a fabric of connectedness between student, teacher, and subject (Palmer, 2007). Teacher-student connection and student engagement are the two most important ingredients in teaching (Lowman, 1995). This paper explores three effective methods of weaving the fabric and engaging students in higher education. Examples of how to use humor, music, and movement to deepen learning while adding energy, engagement, and interaction are offered. A review of research supporting the methods explored in this paper is included.
Within-Subject Interlaboratory Variability of QuantiFERON-TB Gold In-Tube Tests
William C. Whitworth, Lanette R. Hamilton, Donald J. Goodwin, Carlos Barrera, Kevin B. West, Laura Racster, Laura J. Daniels, Stella O. Chuke, Brandon H. Campbell, Jamaria Bohanon, Atheer T. Jaffar, Wanzer Drane, David Maserang, Gerald H. Mazurek
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0043790
Abstract: Background The QuantiFERON?-TB Gold In-Tube test (QFT-GIT) is a viable alternative to the tuberculin skin test (TST) for detecting Mycobacterium tuberculosis infection. However, within-subject variability may limit test utility. To assess variability, we compared results from the same subjects when QFT-GIT enzyme-linked immunosorbent assays (ELISAs) were performed in different laboratories. Methods Subjects were recruited at two sites and blood was tested in three labs. Two labs used the same type of automated ELISA workstation, 8-point calibration curves, and electronic data transfer. The third lab used a different automated ELISA workstation, 4-point calibration curves, and manual data entry. Variability was assessed by interpretation agreement and comparison of interferon-γ (IFN-γ) measurements. Data for subjects with discordant interpretations or discrepancies in TB Response >0.05 IU/mL were verified or corrected, and variability was reassessed using a reconciled dataset. Results Ninety-seven subjects had results from three labs. Eleven (11.3%) had discordant interpretations and 72 (74.2%) had discrepancies >0.05 IU/mL using unreconciled results. After correction of manual data entry errors for 9 subjects, and exclusion of 6 subjects due to methodological errors, 7 (7.7%) subjects were discordant. Of these, 6 (85.7%) had all TB Responses within 0.25 IU/mL of the manufacturer's recommended cutoff. Non-uniform error of measurement was observed, with greater variation in higher IFN-γ measurements. Within-subject standard deviation for TB Response was as high as 0.16 IU/mL, and limits of agreement ranged from ?0.46 to 0.43 IU/mL for subjects with mean TB Response within 0.25 IU/mL of the cutoff. Conclusion Greater interlaboratory variability was associated with manual data entry and higher IFN-γ measurements. Manual data entry should be avoided. Because variability in measuring TB Response may affect interpretation, especially near the cutoff, consideration should be given to developing a range of values near the cutoff to be interpreted as “borderline,” rather than negative or positive.
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