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Search Results: 1 - 10 of 253043 matches for " Daniel C. Williams "
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Analysis of SEC9 Suppression Reveals a Relationship of SNARE Function to Cell Physiology
Daniel C. Williams, Peter J. Novick
PLOS ONE , 2009, DOI: 10.1371/journal.pone.0005449
Abstract: Background Growth and division of Saccharomyces cerevisiae is dependent on the action of SNARE proteins that are required for membrane fusion. SNAREs are regulated, through a poorly understood mechanism, to ensure membrane fusion at the correct time and place within a cell. Although fusion of secretory vesicles with the plasma membrane is important for yeast cell growth, the relationship between exocytic SNAREs and cell physiology has not been established. Methodology/Principal Findings Using genetic analysis, we identified several influences on the function of exocytic SNAREs. Genetic disruption of the V-ATPase, but not vacuolar proteolysis, can suppress two different temperature-sensitive mutations in SEC9. Suppression is unlikely due to increased SNARE complex formation because increasing SNARE complex formation, through overexpression of SRO7, does not result in suppression. We also observed suppression of sec9 mutations by growth on alkaline media or on a non-fermentable carbon source, conditions associated with a reduced growth rate of wild-type cells and decreased SNARE complex formation. Conclusions/Significance Three main conclusions arise from our results. First, there is a genetic interaction between SEC9 and the V-ATPase, although it is unlikely that this interaction has functional significance with respect to membrane fusion or SNAREs. Second, Sro7p acts to promote SNARE complex formation. Finally, Sec9p function and SNARE complex formation are tightly coupled to the physiological state of the cell.
Effects of the Orientation of the Mountainside, Altitude and Varieties on the Quality of the Coffee Beverage from the “Matas de Minas” Region, Brazilian Southeast  [PDF]
Williams P. M. Ferreira, Daniel M. Queiroz, Samuel A. Silvac, Rafael Sim?es Tomaz, Paulo C. Corrêa
American Journal of Plant Sciences (AJPS) , 2016, DOI: 10.4236/ajps.2016.78124
Abstract: Based upon qualitative parameters experiments, this study aims to investigate how the elements of the environment, where the coffee is produced, contribute to the final quality of the product. For the analyses, it was used approximately one kilogram of coffee cherry samples collected in 14 municipalities previously chosen on the East side of the Minas Gerais State, Brazil. The coffee cherry samples were collected and analyzed for each of the two varieties in four levels of altitude for each exposure side of the mountain in relation to the Sun. The quality of the coffee was evaluated through the analysis of its physical characteristics and sensory analysis, popularly known as \"Test of drink or Cupping\" carried out by three tasters that belonging to the group of Q-Graders, according to the rules of national and international competitions of the Brazilian Association of Special Coffees (BSCA). Were performed analysis by means descriptive statistics, analysis of variance and multivariate analysis, all of them aiming to study the individual sensory characteristics of quality of the coffee beverage from the “Matas de Minas” region. Path coefficient analysis also was carried out for the partition of the phenotypic correlation coefficients into measures of direct and indirect effects, in order to determine the individual sensory characteristics that played a major role in the beverage final score. The results demonstrate that it is not possible to conclusively establish the differences among coffees evaluated with basis on varieties and environmental factors previously cited. It can be concluded that it is not recommended to associate the quality of coffee only to a specific factor whether from the environment or being it a specific of the culture of coffee. However, the cafes that were evaluated had intrinsic quality, which were derived from the specific characteristics of the “Matas de Minas” region where they were grown.
Elastic Energy Storage and Radial Forces in the Myofilament Lattice Depend on Sarcomere Length
C. David Williams ,Michael Regnier,Thomas L. Daniel
PLOS Computational Biology , 2012, DOI: 10.1371/journal.pcbi.1002770
Abstract: We most often consider muscle as a motor generating force in the direction of shortening, but less often consider its roles as a spring or a brake. Here we develop a fully three-dimensional spatially explicit model of muscle to isolate the locations of forces and energies that are difficult to separate experimentally. We show the strain energy in the thick and thin filaments is less than one third the strain energy in attached cross-bridges. This result suggests the cross-bridges act as springs, storing energy within muscle in addition to generating the force which powers muscle. Comparing model estimates of energy consumed to elastic energy stored, we show that the ratio of these two properties changes with sarcomere length. The model predicts storage of a greater fraction of energy at short sarcomere lengths, suggesting a mechanism by which muscle function shifts as force production declines, from motor to spring. Additionally, we investigate the force that muscle produces in the radial or transverse direction, orthogonal to the direction of shortening. We confirm prior experimental estimates that place radial forces on the same order of magnitude as axial forces, although we find that radial forces and axial forces vary differently with changes in sarcomere length.
Axial and Radial Forces of Cross-Bridges Depend on Lattice Spacing
C. David Williams ,Michael Regnier,Thomas L. Daniel
PLOS Computational Biology , 2010, DOI: 10.1371/journal.pcbi.1001018
Abstract: Nearly all mechanochemical models of the cross-bridge treat myosin as a simple linear spring arranged parallel to the contractile filaments. These single-spring models cannot account for the radial force that muscle generates (orthogonal to the long axis of the myofilaments) or the effects of changes in filament lattice spacing. We describe a more complex myosin cross-bridge model that uses multiple springs to replicate myosin's force-generating power stroke and account for the effects of lattice spacing and radial force. The four springs which comprise this model (the 4sXB) correspond to the mechanically relevant portions of myosin's structure. As occurs in vivo, the 4sXB's state-transition kinetics and force-production dynamics vary with lattice spacing. Additionally, we describe a simpler two-spring cross-bridge (2sXB) model which produces results similar to those of the 4sXB model. Unlike the 4sXB model, the 2sXB model requires no iterative techniques, making it more computationally efficient. The rate at which both multi-spring cross-bridges bind and generate force decreases as lattice spacing grows. The axial force generated by each cross-bridge as it undergoes a power stroke increases as lattice spacing grows. The radial force that a cross-bridge produces as it undergoes a power stroke varies from expansive to compressive as lattice spacing increases. Importantly, these results mirror those for intact, contracting muscle force production.
Recognition of allergic conjunctivitis in patients with allergic rhinitis
Daniel C Williams, Gabrielle Edney, Bianca Maiden, Peter K Smith
World Allergy Organization Journal , 2013, DOI: 10.1186/1939-4551-6-4
Abstract: One hundred and eighty seven consecutive patients with allergic rhinitis (AR) were directly questioned if they have allergic conjunctivitis (AC) and this was clarified using standard screening questions relating to red, itchy and watery eyes recorded through a total ocular symptom score (TOSS). Patients were also asked about further symptoms that may be attributable to AC: eyelid dermatitis, frequent blinking; eye sensitivity and frontal headache from squinting or. blinking. All patients were given a drop of olopatadine hydrochloride 0.1% in each eye to help identify “silent” disease. 20 healthy non-atopic controls were also treated with olopatadine drops and questioned on ocular symptoms.Fifty five percent of patients with AR were identified as having AC by direct questioning and the use of the TOSS questionaire. A further 41% were identifiable by asking additional questions and performing therapeutic challenge with olopadatine.AC is a frequent comorbid condition occurring in 95% of our patients with AR. Only 55% of patients were able to identify that they had AC based on standard screening questions. Additional specific questioning and a therapeutic challenge in suspected patients can help identify patients who may benefit from treatment of AC.Allergic conjunctivitis (AC) commonly manifests as itchy, watering or red eyes, which comprise the symptoms of the total ocular symptom scores (TOSS) [1-3].The incidence of AC in developed countries is 20% [4-6] with a high co-morbidity of allergic rhinitis (AR) [5,6]. Recognition of AC is unreported even in patients with recognised AR [6,7]. Under-recognition of AR is common, with the proportion of undiagnosed AR patients ranging from 25–60% [8].Clinically, it is apparent that AC patients have heightened sensitivity, tending to blink and squint more, contributing to frontal tension headaches. Rubbing of eyelids can contribute to dermatitis, with patients focusing more on the dermatitis than conjunctival symptoms.Olopatadine
The Framework of a Novel Approach for the Analysis of Human Movement for Clinical Purposes  [PDF]
Mark E. Williams, John C. C. Williams
Open Journal of Social Sciences (JSS) , 2017, DOI: 10.4236/jss.2017.56002
Recent technological advances have led to the development of small wearable microelectronic sensors (accelerometers) that detect motion, gravitational acceleration, and velocity with six degrees of freedom (forward-backward, updown, and side-to-side plus rotational vectors). We have used these motion sensors to create new analytical tools called biokinetographs (BKGs). BKGs allow for more precise screening, diagnosing, monitoring, assessment and predicting of function of elderly people as they ambulate using sophisticated analysis of the unique electronic motion signature of each person. Remarkable visual differences in “functional walking signatures” are evident on the BKGs between fallers and non-fallers. This presentation will summarize our current efforts to translate this new technology into novel clinical and research tools for improving function, reducing injurious falls, and diagnosing orthopedic and neurological conditions for elderly people.
Virginia Woolf’s History of Sexual Victimization: A Case Study in Light of Current Research  [PDF]
Lucia C. A. Williams
Psychology (PSYCH) , 2014, DOI: 10.4236/psych.2014.510128

Virginia Woolf’s history of sexual victimization is presented in a case study format, and reviewed in light of the present literature on the impact of child sexual abuse (CSA) to human development. The methodology to compose the case study involved reviewing the works of Woolf’s main biographers, the author’s memoirs, and the groundbreaking work of Louise DeSalvo, presenting data from Woolf’s diaries and letters, in which sexual abuse is disclosed. Woolf was sexually abused by her two older half-brothers. The abuse was extremely traumatic, and lasted several years. The various mental health symptoms that Woolf experienced are consistent with the literature of CSA. Woolf also presented some adequate coping skills by disclosing the CSA publicly, keeping records of her depressive episodes, and seeking help. Like many incest survivors, Woolf’s sexual abuse was minimized and questioned by biographers. In addition to Woolf’s enormous literary legacy, her knowledge of psychology was impressive. She was a feminist, as well as a visionary in exploring the effects of CSA before other incest survivors. Understanding her life influences is advantageous, not only to literary scholars but to most readers, and mainly clinicians and researchers are interested in the dynamics of sexual abuse.

Dissection of a QTL Hotspot on Mouse Distal Chromosome 1 that Modulates Neurobehavioral Phenotypes and Gene Expression
Khyobeni Mozhui,Daniel C. Ciobanu,Thomas Schikorski,Xusheng Wang,Lu Lu,Robert W. Williams
PLOS Genetics , 2008, DOI: 10.1371/journal.pgen.1000260
Abstract: A remarkably diverse set of traits maps to a region on mouse distal chromosome 1 (Chr 1) that corresponds to human Chr 1q21–q23. This region is highly enriched in quantitative trait loci (QTLs) that control neural and behavioral phenotypes, including motor behavior, escape latency, emotionality, seizure susceptibility (Szs1), and responses to ethanol, caffeine, pentobarbital, and haloperidol. This region also controls the expression of a remarkably large number of genes, including genes that are associated with some of the classical traits that map to distal Chr 1 (e.g., seizure susceptibility). Here, we ask whether this QTL-rich region on Chr 1 (Qrr1) consists of a single master locus or a mixture of linked, but functionally unrelated, QTLs. To answer this question and to evaluate candidate genes, we generated and analyzed several gene expression, haplotype, and sequence datasets. We exploited six complementary mouse crosses, and combed through 18 expression datasets to determine class membership of genes modulated by Qrr1. Qrr1 can be broadly divided into a proximal part (Qrr1p) and a distal part (Qrr1d), each associated with the expression of distinct subsets of genes. Qrr1d controls RNA metabolism and protein synthesis, including the expression of ~20 aminoacyl-tRNA synthetases. Qrr1d contains a tRNA cluster, and this is a functionally pertinent candidate for the tRNA synthetases. Rgs7 and Fmn2 are other strong candidates in Qrr1d. FMN2 protein has pronounced expression in neurons, including in the dendrites, and deletion of Fmn2 had a strong effect on the expression of few genes modulated by Qrr1d. Our analysis revealed a highly complex gene expression regulatory interval in Qrr1, composed of multiple loci modulating the expression of functionally cognate sets of genes.
The value of the pragmatic-explanatory continuum indicator summary wheel in an ongoing study: the bullous pemphigoid steroids and tetracyclines study
Daniel J Bratton, Andrew J Nunn, Fenella Wojnarowska, Gudula Kirtschig, Anna Sandell, Hywel C Williams
Trials , 2012, DOI: 10.1186/1745-6215-13-50
Abstract: Each of the six members of the BLISTER trial team was sent a blank PRECIS wheel to independently complete. The results obtained were averaged and plotted on a single PRECIS wheel to illustrate the degree of pragmatism of the trial.The trial team found that the design of the trial was closest to the pragmatic end of the pragmatic-explanatory continuum. The strongest consensus was found on the ‘flexibility of the comparison intervention’ and ‘practitioner adherence’ domains (SD?=?13). The trial team appeared to disagree most on the ‘eligibility criteria’ (SD?=?35) and ‘participant compliance’ (SD?=?31) domains, although the large standard deviations were a result of a single outlier in the two domains.The PRECIS tool can be used to retrospectively determine the pragmatism of a trial provided enough expertise and information on the trial is available. Illustrating the design of a trial on the PRECIS wheel can help research users more easily identify studies of interest. We hope our recommendations for applying this useful tool will encourage others to consider using it when designing, conducting and reporting studies.Current Controlled Trials http://www.controlled-trials.com/ISRCTN13704604 webcite
OSTEOPAThic Health outcomes In Chronic low back pain: The OSTEOPATHIC Trial
Licciardone John C,King Hollis H,Hensel Kendi L,Williams Daniel G
Osteopathic Medicine and Primary Care , 2008, DOI: 10.1186/1750-4732-2-5
Abstract: Background Osteopathic manipulative treatment (OMT) and ultrasound physical therapy (UPT) are commonly used for chronic low back pain. Although there is evidence from a systematic review and meta-analysis that OMT generally reduces low back pain, there are no large clinical trials that specifically assess OMT efficacy in chronic low back pain. Similarly, there is a lack of evidence involving UPT for chronic low back pain. Methods The OSTEOPAThic Health outcomes In Chronic low back pain (OSTEOPATHIC) Trial is a Phase III randomized controlled trial that seeks to study 488 subjects between August 2006 and June 2010. It uses a 2 × 2 factorial design to independently assess the efficacy of OMT and UPT for chronic low back pain. The primary outcome is a visual analogue scale score for pain. Secondary outcomes include back-specific functioning, generic health, work disability, and satisfaction with back care. Conclusion This randomized controlled trial will potentially be the largest involving OMT. It will provide long awaited data on the efficacy of OMT and UPT for chronic low back pain. Trial registration http://www.clinicaltrials.gov, NCT00315120
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