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Search Results: 1 - 10 of 223864 matches for " Jaclyn R. Stonebraker "
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Mucin Variable Number Tandem Repeat Polymorphisms and Severity of Cystic Fibrosis Lung Disease: Significant Association with MUC5AC
XueLiang Guo, Rhonda G. Pace, Jaclyn R. Stonebraker, Clayton W. Commander, Anthony T. Dang, Mitchell L. Drumm, Ann Harris, Fei Zou, Dallas M. Swallow, Fred A. Wright, Wanda K. O'Neal, Michael R. Knowles
PLOS ONE , 2011, DOI: 10.1371/journal.pone.0025452
Abstract: Variability in cystic fibrosis (CF) lung disease is partially due to non-CFTR genetic modifiers. Mucin genes are very polymorphic, and mucins play a key role in the pathogenesis of CF lung disease; therefore, mucin genes are strong candidates as genetic modifiers. DNA from CF patients recruited for extremes of lung phenotype was analyzed by Southern blot or PCR to define variable number tandem repeat (VNTR) length polymorphisms for MUC1, MUC2, MUC5AC, and MUC7. VNTR length polymorphisms were tested for association with lung disease severity and for linkage disequilibrium (LD) with flanking single nucleotide polymorphisms (SNPs). No strong associations were found for MUC1, MUC2, or MUC7. A significant association was found between the overall distribution of MUC5AC VNTR length and CF lung disease severity (p = 0.025; n = 468 patients); plus, there was robust association of the specific 6.4 kb HinfI VNTR fragment with severity of lung disease (p = 6.2×10?4 after Bonferroni correction). There was strong LD between MUC5AC VNTR length modes and flanking SNPs. The severity-associated 6.4 kb VNTR allele of MUC5AC was confirmed to be genetically distinct from the 6.3 kb allele, as it showed significantly stronger association with nearby SNPs. These data provide detailed respiratory mucin gene VNTR allele distributions in CF patients. Our data also show a novel link between the MUC5AC 6.4 kb VNTR allele and severity of CF lung disease. The LD pattern with surrounding SNPs suggests that the 6.4 kb allele contains, or is linked to, important functional genetic variation.
Recent Advances in Arctic Ocean Studies Employing Models from the Arctic Ocean Model Intercomparison Project
Andrey Proshutinsky,Yevgeny Aksenov |,Jaclyn Clement Kinney,Rüdiger Gerdes
Oceanography , 2011,
Abstract: Observational data show that the Arctic Ocean has significantly and rapidly changed over the last few decades, which is unprecedented in the observational record. Air and water temperatures have increased, sea ice volume and extent have decreased, permafrost has thawed, storminess has increased, sea level has risen, coastal erosion has progressed, and biological processes have become more complex and diverse. In addition, there are socio-economic impacts of Arctic environmental change on Arctic residents and the world, associated with tourism, oil and gas exploration, navigation, military operations, trade, and industry. This paper discusses important results of the Arctic Ocean Model Intercomparison Project, which is advancing the role of numerical modeling in Arctic Ocean and sea ice research by stimulating national and international synergies for high-latitude research.
On the image of the Galois representation associated to a non-CM Hida family
Jaclyn Lang
Mathematics , 2014,
Abstract: Fix a prime $p > 2$. Let $\rho : \text{Gal}(\overline{\mathbb{Q}}/\mathbb{Q}) \to \text{GL}_2(\mathbb{I})$ be the Galois representation coming from a non-CM irreducible component $\mathbb{I}$ of Hida's $p$-ordinary Hecke algebra. Assume the residual representation $\bar{\rho}$ is absolutely irreducible. Under a minor technical condition we identify a subring $\mathbb{I}_0$ of $\mathbb{I}$ containing $\mathbb{Z}_p[[T]]$ such that the image of $\rho$ is large with respect to $\mathbb{I}_0$. That is, $\text{Im} \rho$ contains $\text{ker}(\text{SL}_2(\mathbb{I}_0) \to \text{SL}_2(\mathbb{I}_0/\mathfrak{a}))$ for some non-zero $\mathbb{I}_0$-ideal $\mathfrak{a}$. This paper builds on recent work of Hida who showed that the image of such a Galois representation is large with respect to $\mathbb{Z}_p[[T]]$. Our result is an $\mathbb{I}$-adic analogue of the description of the image of the Galois representation attached to a non-CM classical modular form obtained by Ribet and Momose in the 1980s.
High-fat diet accelerates progression of osteoarthritis after meniscal/ligamentous injury
Robert A Mooney, Erik R Sampson, Jaclyn Lerea, Randy N Rosier, Michael J Zuscik
Arthritis Research & Therapy , 2011, DOI: 10.1186/ar3529
Abstract: Five-week-old C57BL/6 mice were placed on HF (60% kcal) or low-fat (lean, 10% kcal) diets for 8 or 12 weeks before transecting the medial collateral ligament and excising a segment of the medial meniscus of the knee to initiate OA. One group was switched from lean to HF diet at the time of surgery.Body weight of mice on the HF diet peaked at 45.9 ± 2.1 g compared with 29.9 ± 1.8 g for lean diets, with only those on the HF becoming diabetic. Severity of OA was greater in HF mice, evidenced by the Osteoarthritis Research Society International (OARSI) histopathology initiative scoring method for mice and articular cartilage thickness and area. To assess the importance of weight gain, short- and long-term HF diets were compared with the lean diet. Short- and long-term HF groups outweighed lean controls by 6.2 g and 20.5 g, respectively. Both HF groups became diabetic, and OA progression, evidenced by increased OARSI score, decreased cartilage thickness, and increased osteophyte diameter, was comparably accelerated relative to those of lean controls.These results demonstrate that the HF diet accelerates progression of OA in a type 2 diabetic mouse model without correlation to weight gain, suggesting that metabolic dysregulation is a comorbid factor in OA-related cartilage degeneration.Decreased physical activity and the consumption of a high-fat Western diet have contributed to a worldwide epidemic of obesity and associated type 2 diabetes [1]. As a result, the incidence of cardiovascular disease, hypertension, cancer, nonalcoholic fatty liver disease, stroke, and other secondary complications is anticipated to be negatively affected [2,3]. One additional consequence of this epidemic is an increased incidence of osteoarthritis (OA) in both weight-bearing and non-weight-bearing joints [4,5], with more than 50% of those with diabetes having some form of arthritis [4]. In the United States, 52.1% of patients receiving knee replacements in 2005 were obese [6]. In Canada, 87%
Inhaled nitric oxide reverses cell-free hemoglobin-induced pulmonary hypertension and decreased lung compliance. Preliminary results
Luiz F Poli de Figueiredo, Mali Mathru, Jaclyn R Jones, Daneshvari Solanki, George C Kramer
Critical Care , 1998, DOI: 10.1186/cc114
Abstract: ααHb caused pulmonary arterial pressure (PAP) to increase from 27 ± 1.7 to 40 ± 3.0 mmHg (P<0.05) and dynamic lung compliance to decrease from 29± 1.5 to 23± 1.6 ml/cmH2O (P < 0.05). After both doses of inhaled NO, but particularly 10 ppm, PAP was reduced (P < 0.05) and lung compliance increased (P < 0.05) from the ααHb levels. When inhaled NO was discontinued PAP again increased and lung compliance decreased to levels significantly different from baseline (P < 0.05).We conclude that cell-free hemoglobin-induced pulmonary hypertension and decreased lung compliance can be selectively counteracted by inhaled NO.Cell-free hemoglobin oxygen-carrying solutions are now undergoing clinical trials. Such solutions may overcome the limitations of homologous blood transfusion. Preservation of cardiovascular function and oxygen transport has been demonstrated after partial and complete exchange transfusion with cell-free hemoglobin solutions [1,2,3,4]. Hemoglobin solutions may have potential particularly as a resuscitative fluid due to their pharmacological actions, which cause increases in arterial pressure and blood flow even in small doses [5,6].However, it has been demonstrated that pulmonary hypertension, leading to hypoxemia and hemodynamic instability, may offset the benefits of cell-free hemoglobin blood substitutes [7,8,9,10,11]. The main mechanism by which these solutions produce vasoconstriction is by binding and inactivating nitric oxide (NO) [12,13,14], a key mediator responsible for the physiological regulation of the vasodilatory tone.Selective pulmonary vasodilation with inhaled NO administration has been widely demonstrated in animal models and in patients with pulmonary hypertension [15,16,17].Selective pulmonary vasodilation occurs because inhaled NO is rapidly inactivated by hemoglobin as it enters the circulation; hemoglobin's affinity for NO is many thousand times greater than for either oxygen or carbon monoxide [18,19,20]. It has also been shown that inh
Embracing Pharmacy E-Learning: Models of Success
Jaclyn A. Jeffries,Pamela R. Jeffries,John B. Hertig,Kyle E. Hultgren
Pharmacy , 2013, DOI: 10.3390/pharmacy1010043
Abstract: Traditionally, education has revolved around the idea of a learner being taught in a physical classroom setting. With recent technological developments and the “immediate results” world we now live in, elearning has become much more common. Students and professionals are now able to access and acquire lectures, tests, certifications and degrees online. The Purdue University College of Pharmacy’s Center for Medication Safety Advancement has developed three eresources to enhance medication safety: The Veterans Affairs Yellow Belt Lean Certification Course, the Medication Safety Essentials Continuing Education Modules, and the Virtual Clean Room Simulation Certificate. These three modalities offer valuable content for additional knowledge, training and certification at a convenient location—your computer.
UK DRAFFT - A randomised controlled trial of percutaneous fixation with kirschner wires versus volar locking-plate fixation in the treatment of adult patients with a dorsally displaced fracture of the distal radius
Matthew L Costa, Juul Achten, Nick R Parsons, Amar Rangan, Richard P Edlin, Jaclyn Brown, Sarah E Lamb
BMC Musculoskeletal Disorders , 2011, DOI: 10.1186/1471-2474-12-201
Abstract: All adult patients with an acute, dorsally-displaced fracture of the distal radius, requiring operative fixation are potentially eligible to take part in this study. A total of 390 consenting patients will be randomly allocated to either K-wire fixation or locking-plate fixation. The surgery will be performed in trauma units across the UK using the preferred technique of the treating surgeon. Data regarding wrist function, quality of life, complications and costs will be collected at six weeks and three, six and twelve months following the injury. The primary outcome measure will be wrist function with a parallel economic analysis.This pragmatic, multi-centre trial is due to deliver results in December 2013.Current Controlled Trials ISRCTN31379280UKCRN portfolio ID 8956Fractures of the distal radius are extremely common injuries. In the Western World, 6% of women will have sustained such a fracture by the age of 80 and 9% by the age of 90 [1]. The optimal management of fractures of the distal radius in adults remains controversial. There is a bimodal distribution in terms of age. Younger patients frequently sustain complicated, high-energy injuries involving the wrist joint. However, fractures of the distal radius are also common in older patients who are more likely to sustain low-energy fractures, often related to osteoporosis [2] This study is designed to address both groups of patients as the key management issues pertain to all patients with a fracture of the distal radius.In general, fractures of the distal radius are treated non-operatively if the bone fragments are undisplaced or the fragments can be held in anatomical alignment (reduction) by a plaster cast or orthotic. However, if this is not possible then operative fixation is required. This carries inherent risks for the patient and considerable cost implications for the NHS; much of this cost is related to the choice of fixation [3].There are several operative options but the two most common in the UK,
Assessing the Role of STAT3 in DC Differentiation and Autologous DC Immunotherapy in Mouse Models of GBM
Hikmat Assi, Jaclyn Espinosa, Sarah Suprise, Michael Sofroniew, Robert Doherty, Daniel Zamler, Pedro R. Lowenstein, Maria G. Castro
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0096318
Abstract: Cellular microenvironments, particularly those found in tumors, elicit a tolerogenic DC phenotype which can attenuate immune responses. Central to this process is the STAT3-mediated signaling cascade. As a transcription factor and oncogene, STAT3 promotes the expression of genes which allow tumor cells to proliferate, migrate and evade apoptosis. More importantly, activation of STAT3 in tumor infiltrating immune cells has been shown to be responsible, in part, for their immune-suppressed phenotype. The ability of STAT3 to orchestrate a diverse set of immunosuppressive instructions has made it an attractive target for cancer vaccines. Using a conditional hematopoietic knockout mouse model of STAT3, we evaluated the impact of STAT3 gene ablation on the differentiation of dendritic cells from bone marrow precursors. We also assessed the impact of STAT3 deletion on phagocytosis, maturation, cytokine secretion and antigen presentation by GM-CSF derived DCs in vitro. In addition to in vitro studies, we compared the therapeutic efficacy of DC vaccination using STAT3 deficient DCs to wild type counterparts in an intracranial mouse model of GBM. Our results indicated the following pleiotropic functions of STAT3: hematopoietic cells which lacked STAT3 were unresponsive to Flt3L and failed to differentiate as DCs. In contrast, STAT3 was not required for GM-CSF induced DC differentiation as both wild type and STAT3 null bone marrow cells gave rise to similar number of DCs. STAT3 also appeared to regulate the response of GM-CSF derived DCs to CpG. STAT3 null DCs expressed high levels of MHC-II, secreted more IL-12p70, IL-10, and TNFα were better antigen presenters in vitro. Although STAT3 deficient DCs displayed an enhanced activated phenotype in culture, they elicited comparable therapeutic efficacy in vivo compared to their wild type counterparts when utilized in vaccination paradigms in mice bearing intracranial glioma tumors.
The Chemical Synthesis of Tetrodoxin: An Ongoing Quest
Jaclyn Chau,Marco A. Ciufolini
Marine Drugs , 2011, DOI: 10.3390/md9102046
Abstract: This contribution reviews all the synthetic work on tetrodotoxin that has appeared in the literature through June 2011.
Abundance and home ranges of feral cats in an urban conservancy where there is supplemental feeding: a case study from South Africa
Jaclyn Tennent,Colleen T. Downs
African Zoology , 2011,
Abstract: There is much debate surrounding the impact of feral cats (Felis catus) on wildlife. Conservancies are usually areas where indigenous flora and fauna are protected and aliens excluded or managed. The University of KwaZulu-Natal’s Howard College campus (HCC) is an urban conservancy containing feral cats that are presently not managed, and little is known about their ecology and behaviour. Consequently a feral cat population census was conducted, and their home range investigated. Estimates of the overall campus feral cat population numbers ranged between 23.4–40.0 cats/km2 with a minimum of 55 identified as resident. They were not randomly distributed in the study area, with spacing patterns being related to resource availability. Home range area and core distribution of eight radio-collared cats were determined over 13 months. Total home range areas were relatively small, with considerable overlap between them. Home ranges were clustered in areas with permanent feeding stations and these were also within the cats’ core ranges. Supp
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