Showing papers by "University of Kentucky published in 2008"
TL;DR: Regression and mediation analyses showed that several of the facets of the Five Facet Mindfulness Questionnaire contributed independently to the prediction of well-being and significantly mediated the relationship between meditation experience andWell-being.
Abstract: Previous research on assessment of mindfulness by self-report suggests that it may include five component skills: observing, describing, acting with awareness, nonjudging of inner experience, and nonreactivity to inner experience. These elements of mindfulness can be measured with the Five Facet Mindfulness Questionnaire (FFMQ). The authors investigated several aspects of the construct validity of the FFMQ in experienced meditators and nonmeditating comparison groups. Consistent with predictions, most mindfulness facets were significantly related to meditation experience and to psychological symptoms and well-being. As expected, relationships between the observing facet and psychological adjustment varied with meditation experience. Regression and mediation analyses showed that several of the facets contributed independently to the prediction of well-being and significantly mediated the relationship between meditation experience and well-being. Findings support the construct validity of the FFMQ in a combination of samples not previously investigated.
2,294 citations
TL;DR: New approaches to add functionality were developed to improve the processability of these materials in solution, allowing the synthesis of acenes larger than pentacene, which have hitherto been largely unavailable and poorly studied.
Abstract: Acenes have long been the subject of intense study because of the unique electronic properties associated with their pi-bond topology. Recent reports of impressive semiconductor properties of larger homologues have reinvigorated research in this field, leading to new methods for their synthesis, functionalization, and purification, as well as for fabricating organic electronic components. Studies performed on high-purity acene single crystals revealed their intrinsic electronic properties and provide useful benchmarks for thin film device research. New approaches to add functionality were developed to improve the processability of these materials in solution. These new functionalization strategies have recently allowed the synthesis of acenes larger than pentacene, which have hitherto been largely unavailable and poorly studied, as well as investigation of their associated structure/property relationships.
1,741 citations
TL;DR: Increases in mindfulness were found to mediate the relationships between formal mindfulness practice and improvements in psychological functioning, suggesting that the practice of mindfulness meditation leads to increases in mindfulness, which in turn leads to symptom reduction and improved well-being.
Abstract: Relationships were investigated between home practice of mindfulness meditation exercises and levels of mindfulness, medical and psychological symptoms, perceived stress, and psychological well-being in a sample of 174 adults in a clinical Mindfulness-Based Stress Reduction (MBSR) program. This is an 8- session group program for individuals dealing with stress-related problems, illness, anxiety, and chronic pain. Participants completed measures of mindfulness, perceived stress, symptoms, and well-being at pre- and post-MBSR, and monitored their home practice time throughout the intervention. Results showed increases in mindfulness and well-being, and decreases in stress and symptoms, from pre- to post-MBSR. Time spent engaging in home practice of formal meditation exercises (body scan, yoga, sitting meditation) was significantly related to extent of improvement in most facets of mindfulness and several measures of symptoms and well-being. Increases in mindfulness were found to mediate the relationships between formal mindfulness practice and improvements in psychological functioning, suggesting that the practice of mindfulness meditation leads to increases in mindfulness, which in turn leads to symptom reduction and improved well-being.
1,641 citations
TL;DR: Defects in MMR are associated with genome-wide instability, predisposition to certain types of cancer including hereditary non-polyposis colorectal cancer, resistance to certain chemotherapeutic agents, and abnormalities in meiosis and sterility in mammalian systems.
Abstract: DNA mismatch repair (MMR) is a highly conserved biological pathway that plays a key role in maintaining genomic stability. The specificity of MMR is primarily for base-base mismatches and insertion/deletion mispairs generated during DNA replication and recombination. MMR also suppresses homeologous recombination and was recently shown to play a role in DNA damage signaling in eukaryotic cells. Escherichia coli MutS and MutL and their eukaryotic homologs, MutSalpha and MutLalpha, respectively, are key players in MMR-associated genome maintenance. Many other protein components that participate in various DNA metabolic pathways, such as PCNA and RPA, are also essential for MMR. Defects in MMR are associated with genome-wide instability, predisposition to certain types of cancer including hereditary non-polyposis colorectal cancer, resistance to certain chemotherapeutic agents, and abnormalities in meiosis and sterility in mammalian systems.
1,188 citations
TL;DR: The electronic structure of 5d transition-metal oxide Sr2IrO4 is investigated using angle-resolved photoemission, optical conductivity, x-ray absorption measurements, and first-principles band calculations, suggesting a new class of Jeff quantum spin driven correlated-electron phenomena.
Abstract: We investigated the electronic structure of 5d transition-metal oxide Sr2IrO4 using angle-resolved photoemission, optical conductivity, x-ray absorption measurements, and first-principles band calculations. The system was found to be well described by novel effective total angular momentum Jeff states, in which the relativistic spin-orbit coupling is fully taken into account under a large crystal field. Despite delocalized Ir 5d states, the Jeff states form such narrow bands that even a small correlation energy leads to the Jeff=1/2 Mott ground state with unique electronic and magnetic behaviors, suggesting a new class of Jeff quantum spin driven correlated-electron phenomena.
1,110 citations
TL;DR: In this paper, a review of the theorized sources of self-efficacy beliefs proposed by A. Bandura (1986) are described and explained, including how they are typically assessed and analyzed, and problems and oversights in current research and in conceptualizations of the sources.
Abstract: The purpose of this review was threefold. First, the theorized sources of self-efficacy beliefs proposed by A. Bandura (1986) are described and explained, including how they are typically assessed and analyzed. Second, findings from investigations of these sources in academic contexts are reviewed and critiqued, and problems and oversights in current research and in conceptualizations of the sources are identified. Although mastery experience is typically the most influential source of self-efficacy, the strength and influence of the sources differ as a function of contextual factors such as gender, ethnicity, academic ability, and academic domain. Finally, suggestions are offered to help guide researchers investigating the psychological mechanisms at work in the formation of self-efficacy beliefs in academic contexts.
1,087 citations
TL;DR: Subjects with GOLD stage 3 or 4 COPD had a higher prevalence of diabetes, which contributes to a higher risk of adverse outcomes of mortality and hospitalisations, and subjects with impaired lung function had more comorbid disease.
Abstract: Chronic obstructive pulmonary disease (COPD) is associated with important chronic comorbid diseases, including cardiovascular disease, diabetes and hypertension. The present study analysed data from 20,296 subjects aged > or =45 yrs at baseline in the Atherosclerosis Risk in Communities Study (ARIC) and the Cardiovascular Health Study (CHS). The sample was stratified based on baseline lung function data, according to modified Global Initiative for Obstructive Lung Disease (GOLD) criteria. Comorbid disease at baseline and death and hospitalisations over a 5-yr follow-up were then searched for. Lung function impairment was found to be associated with more comorbid disease. In logistic regression models adjusting for age, sex, race, smoking, body mass index and education, subjects with GOLD stage 3 or 4 COPD had a higher prevalence of diabetes (odds ratio (OR) 1.5, 95% confidence interval (CI) 1.1-1.9), hypertension (OR 1.6, 95% CI 1.3-1.9) and cardiovascular disease (OR 2.4, 95% CI 1.9-3.0). Comorbid disease was associated with a higher risk of hospitalisation and mortality that was worse in people with impaired lung function. Lung function impairment is associated with a higher risk of comorbid disease, which contributes to a higher risk of adverse outcomes of mortality and hospitalisations.
982 citations
TL;DR: A new, multidimensional classification system should be developed for TBI clinical trials and it was agreed that preclinical models were vital in establishing pathophysiologic mechanisms relevant to specific pathoanatomic types of TBI and verifying that a given therapeutic approach improves outcome in these targeted TBI types.
Abstract: The heterogeneity of traumatic brain injury (TBI) is considered one of the most significant barriers to finding effective therapeutic interventions. In October, 2007, the National Institute of Neurological Disorders and Stroke, with support from the Brain Injury Association of America, the Defense and Veterans Brain Injury Center, and the National Institute of Disability and Rehabilitation Research, convened a workshop to outline the steps needed to develop a reliable, efficient and valid classification system for TBI that could be used to link specific patterns of brain and neurovascular injury with appropriate therapeutic interventions. Currently, the Glasgow Coma Scale (GCS) is the primary selection criterion for inclusion in most TBI clinical trials. While the GCS is extremely useful in the clinical management and prognosis of TBI, it does not provide specific information about the pathophysiologic mechanisms which are responsible for neurological deficits and targeted by interventions. On th...
948 citations
TL;DR: It is shown that generic siRNAs might treat angiogenic disorders that affect 8% of the world’s population, and that si RNAs might induce unanticipated vascular or immune effects.
Abstract: Clinical trials of small interfering RNA (siRNA) targeting vascular endothelial growth factor-A (VEGFA) or its receptor VEGFR1 (also called FLT1), in patients with blinding choroidal neovascularization (CNV) from age-related macular degeneration, are premised on gene silencing by means of intracellular RNA interference (RNAi). We show instead that CNV inhibition is a siRNA-class effect: 21-nucleotide or longer siRNAs targeting non-mammalian genes, non-expressed genes, non-genomic sequences, pro- and anti-angiogenic genes, and RNAi-incompetent siRNAs all suppressed CNV in mice comparably to siRNAs targeting Vegfa or Vegfr1 without off-target RNAi or interferon-α/β activation. Non-targeted (against non-mammalian genes) and targeted (against Vegfa or Vegfr1) siRNA suppressed CNV via cell-surface toll-like receptor 3 (TLR3), its adaptor TRIF, and induction of interferon-γ and interleukin-12. Non-targeted siRNA suppressed dermal neovascularization in mice as effectively as Vegfa siRNA. siRNA-induced inhibition of neovascularization required a minimum length of 21 nucleotides, a bridging necessity in a modelled 2:1 TLR3–RNA complex. Choroidal endothelial cells from people expressing the TLR3 coding variant 412FF were refractory to extracellular siRNA-induced cytotoxicity, facilitating individualized pharmacogenetic therapy. Multiple human endothelial cell types expressed surface TLR3, indicating that generic siRNAs might treat angiogenic disorders that affect 8% of the world’s population, and that siRNAs might induce unanticipated vascular or immune effects.
895 citations
TL;DR: This paper surveys the state of art in securing wireless sensor networks, with an emphasis on authentication, key management and distribution, secure routing, and methods for intrusion detection.
Abstract: With sensor networks on the verge of deployment, security issues pertaining to the sensor networks are in the limelight. Though the security in sensor networks share many characteristics with wireless ad hoc networks, the two fields are rapidly diverging due to the fundamental differences between the make-up and goals of the two types of networks. Perhaps the greatest dividing difference is the energy and computational abilities. Sensor nodes are typically smaller, less powerful, and more prone to failure than nodes in an ad hoc network. These differences indicate that protocols that are valid in the context of ad-hoc networks may not be directly applicable for sensor networks. In this paper, we survey the state of art in securing wireless sensor networks. We review several protocols that provide security in sensor networks, with an emphasis on authentication, key management and distribution, secure routing, and methods for intrusion detection. Copyright © 2006 John Wiley & Sons, Ltd.
879 citations
TL;DR: In this article, the authors review advances in sensor technology, particularly emerging geophysical methods and distributed sensors, aimed at bridging this gap and offer a vision for future research, listing many of the current scientific and technical challenges.
Abstract: At the watershed scale, soil moisture is the major control for rainfall–runoff response, especially where saturation excess runoff processes dominate. From the ecological point of view, the pools of soil moisture are fundamental ecosystem resources providing the transpirable water for plants. In drylands particularly, soil moisture is one of the major controls on the structure, function, and diversity in ecosystems. In terms of the global hydrological cycle, the overall quantity of soil moisture is small, ∼0.05%; however, its importance to the global energy balance and the distribution of precipitation far outweighs its physical amount. In soils it governs microbial activity that affects important biogeochemical processes such as nitrification and CO2 production via respiration. During the past 20 years, technology has advanced considerably, with the development of different electrical sensors for determining soil moisture at a point. However, modeling of watersheds requires areal averages. As a result, point measurements and modeling grid cell data requirements are generally incommensurate. We review advances in sensor technology, particularly emerging geophysical methods and distributed sensors, aimed at bridging this gap. We consider some of the data analysis methods for upscaling from a point to give an areal average. Finally, we conclude by offering a vision for future research, listing many of the current scientific and technical challenges.
TL;DR: The empirical FFM profiles generated for each personality disorder were generally congruent at the facet level with hypothesized FFM translations of the DSM-IV-TR personality disorders, but notable exceptions to the hypotheses did occur and even some findings that were consistent with FFM theory could be said to be instrument specific.
TL;DR: Evidence is presented for the existence of 2 related traits called positive andnegative urgency, which refer to individual differences in the disposition to engage in rash action when experiencing extreme positive and negative affect, respectively.
Abstract: Under heightened emotional states, individuals are more inclined to engage in ill-considered or rash actions than at other times. The authors present evidence for the existence of 2 related traits called positive and negative urgency. The traits refer to individual differences in the disposition to engage in rash action when experiencing extreme positive and negative affect, respectively. The authors provide evidence that these traits are distinct from other dispositions toward rash action and that they play distinct roles in predicting problem levels of involvement in behaviors such as alcohol consumption, binge eating, drug use, and risky sexual behavior. The authors identify facilitative conditions for the emergence of the urgency traits from neuroscience. Certain gene polymorphisms are associated with low levels of serotonin and high levels of dopamine; that pattern of neurotransmitter activity in a brain system linking the orbitofrontal cortex and the amygdala appears to facilitate the development of positive and negative urgency. The authors discuss the implications of this theory.
TL;DR: A system for automatic, geo-registered, real-time 3D reconstruction from video of urban scenes that extends existing algorithms to meet the robustness and variability necessary to operate out of the lab and shows results on real video sequences comprising hundreds of thousands of frames.
Abstract: The paper presents a system for automatic, geo-registered, real-time 3D reconstruction from video of urban scenes. The system collects video streams, as well as GPS and inertia measurements in order to place the reconstructed models in geo-registered coordinates. It is designed using current state of the art real-time modules for all processing steps. It employs commodity graphics hardware and standard CPU's to achieve real-time performance. We present the main considerations in designing the system and the steps of the processing pipeline. Our system extends existing algorithms to meet the robustness and variability necessary to operate out of the lab. To account for the large dynamic range of outdoor videos the processing pipeline estimates global camera gain changes in the feature tracking stage and efficiently compensates for these in stereo estimation without impacting the real-time performance. The required accuracy for many applications is achieved with a two-step stereo reconstruction process exploiting the redundancy across frames. We show results on real video sequences comprising hundreds of thousands of frames.
TL;DR: In this article, a clumpy torus model with N{sub 0} {approx} 5-15 dusty clouds along radial equatorial rays successfully explain AGN infrared observations.
Abstract: Clumpy torus models with N{sub 0} {approx} 5-15 dusty clouds along radial equatorial rays successfully explain AGN infrared observations. The dust has standard Galactic composition, with individual cloud optical depth {tau}{sub V} {approx} 30-100 at visual. The models naturally explain the observed behavior of the 10 {mu}m silicate feature, in particular the lack of deep absorption features in AGNs of any type, and can reproduce the weak emission feature tentatively detected in type 2 QSOs. The clouds' angular distribution must have a soft edge, e.g., Gaussian, and the radial distribution should decrease as 1/r or 1/r{sup 2}. In line with recent interferometry, the ratio of the torus outer to inner radius can be as small as {approx}5-10. The models can produce nearly isotropic IR emission together with highly anisotropic obscuration, as required by observations. Clumpiness implies that the viewing angle determines an AGN classification only probabilistically; a source can display type 1 properties even from directions close to the equatorial plane. The fraction of obscured sources depends not only on the torus angular thickness but also on the cloud number N{sub 0}, and this fraction's observed decrease with luminosity can be explained with a decrease of either parameter. X-ray obscuration,more » too, is probabilistic; resulting from both dusty and dust-free clouds, it might be dominated by the latter, giving rise to the observed QSOs that are X-ray obscured. Observations indicate that the torus and broad-line-emitting clouds form a seamless distribution, with the transition between the two caused by dust sublimation. Torus clouds may have been detected in the outflow component of H{sub 2}O maser emission from two AGNs. Proper-motion measurements of outflow masers, especially in Circinus, are a promising method for probing the morphology and kinematics of torus clouds.« less
TL;DR: Together, the coordinated application of miRNA profiling, Affymetrix microarrays, new bioinformatics predictions, in situ hybridization, and biochemical validation indicate that miR-107 may be involved in accelerated disease progression through regulation of BACE1.
Abstract: MicroRNAs (miRNAs) are small regulatory RNAs that participate in posttranscriptional gene regulation in a sequence-specific manner. However, little is understood about the role(s) of miRNAs in Alzheimer's disease (AD). We used miRNA expression microarrays on RNA extracted from human brain tissue from the University of Kentucky Alzheimer's Disease Center Brain Bank with near-optimal clinicopathological correlation. Cases were separated into four groups: elderly nondemented with negligible AD-type pathology, nondemented with incipient AD pathology, mild cognitive impairment (MCI) with moderate AD pathology, and AD. Among the AD-related miRNA expression changes, miR-107 was exceptional because miR-107 levels decreased significantly even in patients with the earliest stages of pathology. In situ hybridization with cross-comparison to neuropathology demonstrated that particular cerebral cortical laminas involved by AD pathology exhibit diminished neuronal miR-107 expression. Computational analysis predicted that the 3′-untranslated region (UTR) of β-site amyloid precursor protein-cleaving enzyme 1 (BACE1) mRNA is targeted multiply by miR-107. From the same RNA material analyzed on miRNA microarrays, mRNA expression profiling was performed using Affymetrix Exon Array microarrays on nondemented, MCI, and AD patients. BACE1 mRNA levels tended to increase as miR-107 levels decreased in the progression of AD. Cell culture reporter assays performed with a subset of the predicted miR-107 binding sites indicate the presence of at least one physiological miR-107 miRNA recognition sequence in the 3′-UTR of BACE1 mRNA. Together, the coordinated application of miRNA profiling, Affymetrix microarrays, new bioinformatics predictions, in situ hybridization, and biochemical validation indicate that miR-107 may be involved in accelerated disease progression through regulation of BACE1.
TL;DR: The addition of gemcitabine to adjuvant fluorouracil-based chemoradiation was associated with a survival benefit for patients with resected pancreatic cancer, although this improvement was not statistically significant.
Abstract: Context Among patients with locally advanced metastatic pancreatic adenocarcinoma,
gemcitabine has been shown to improve outcomes compared with fluorouracil. Objective To determine if the addition of gemcitabine to adjuvant fluorouracil chemoradiation (chemotherapy plus radiation) improves survival for patients with resected pancreatic adenocarcinoma. Design, Setting, and Participants Randomized controlled phase 3 trial of patients with complete gross total resection of pancreatic adenocarcinoma and no prior radiation or chemotherapy enrolled between July 1998 and July 2002 with follow-up through August 18, 2006, at 164 US and Canadian institutions. Intervention Chemotherapy with either fluorouracil (continuous infusion of 250 mg/m 2 per day; n = 230) or gemcitabine (30-minute infusion of 1000 mg/m 2 once per week; n = 221)
for 3 weeks prior to chemoradiation therapy and for 12 weeks after chemoradiation therapy. Chemoradiation with a continuous infusion of fluorouracil (250 mg/m 2 per day) was the same for all patients (50.4 Gy). Main Outcome Measures Survival for all patients and survival for patients with pancreatic head tumors were the primary end points. Secondary end points included toxicity. Results A total of 451 patients were randomized, eligible, and analyzable.
Patients with pancreatic head tumors (n = 388) had a median survival of 20.5 months and a 3-year survival of 31% in the gemcitabine group vs a median survival of 16.9 months and a 3-year survival of 22% in the fluorouracil group (hazard ratio, 0.82 [95% confidence interval, 0.65-1.03]; P = .09).
The treatment effect was strengthened on multivariate analysis (hazard ratio, 0.80 [95% confidence interval, 0.63-1.00]; P = .05). Grade 4 hematologic toxicity was 1% in the fluorouracil group and 14% in the gemcitabine group (P 85%). Conclusions The addition of gemcitabine to adjuvant fluorouracil-based chemoradiation was associated with a survival benefit for patients with resected pancreatic cancer, although this improvement was not statistically significant. Trial Registration clinicaltrials.gov Identifier: NCT00003216
TL;DR: The newly discovered role of p53 in regulating cellular ROS generation and how ROS modulate selective transactivation of certain p53 target genes are examined, with a focus on interlinks between ROS and p53.
TL;DR: This study suggests that neuro-inflammatory reaction could contribute to AD pathology, and anti-inflammatory agent could be useful for the prevention of AD.
Abstract: Alzheimer's disease (AD) is characterized by extensive loss of neurons in the brain of AD patients. Intracellular accumulation of beta-amyloid peptide (Aβ) has also shown to occur in AD. Neuro-inflammation has been known to play a role in the pathogenesis of AD. In this study, we investigated neuro-inflammation and amyloidogenesis and memory impairment following the systemic inflammation generated by lipopolysaccharide (LPS) using immunohistochemistry, ELISA, behavioral tests and Western blotting. Intraperitoneal injection of LPS, (250 μg/kg) induced memory impairment determined by passive avoidance and water maze tests in mice. Repeated injection of LPS (250 μg/kg, 3 or 7 times) resulted in an accumulation of Aβ1–42 in the hippocampus and cerebralcortex of mice brains through increased β- and γ-secretase activities accompanied with the increased expression of amyloid precursor protein (APP), 99-residue carboxy-terminal fragment of APP (C99) and generation of Aβ1–42 as well as activation of astrocytes in vivo. 3 weeks of pretreatment of sulindac sulfide (3.75 and 7.5 mg/kg, orally), an anti-inflammatory agent, suppressed the LPS-induced amyloidogenesis, memory dysfunction as well as neuronal cell death in vivo. Sulindac sulfide (12.5–50 μM) also suppressed LPS (1 μg/ml)-induced amyloidogenesis in cultured neurons and astrocytes in vitro. This study suggests that neuro-inflammatory reaction could contribute to AD pathology, and anti-inflammatory agent could be useful for the prevention of AD.
TL;DR: In this paper, it was shown that in a clumpy medium, a large range of dust temperatures coexist at the same distance from the radiation central source, which explains the low dust temperatures found close to the nucleus of NGC 1068 in 10� m interferometric observations.
Abstract: Accordingtounifiedschemesof activegalactic nuclei(AGNs), thecentralengine issurroundedbydusty,optically thickcloudsinatoroidalstructure.Wehaverecentlydevelopedaformalismthatforthefirsttimetakesproperaccount of the clumpy nature of the AGN torus. We now provide a detailed report of our findings in a two-paper series. Here wepresentourgeneralformalismforradiativetransferinclumpymediaandconstructitsbuildingblocksfortheAGN problem—the source functions of individual dusty clouds heated by the AGN radiation field. We show that a fundamental difference from smooth density distributions is that in a clumpy medium, a large range of dust temperatures coexist at the same distance from the radiation central source. This distinct property explains the low dust temperatures found close to the nucleus of NGC 1068 in 10� m interferometric observations. Wefind that, irrespective of the overallgeometry,aclumpydustdistributionshowsonlymoderate variationinitsspectralenergydistribution, andthe 10� mabsorptionfeatureisneverdeep.Furthermore,theX-rayattenuatingcolumndensityiswidelyscatteredaround the column density that characterizes the IR emission. All of these properties are characteristic of AGN observations. The assembly of clouds into AGN tori and comparison with observations are presented in the companion paper. Subject headingg dust, extinction — galaxies: active — galaxies: Seyfert — infrared: general — quasars: general — radiative transfer
TL;DR: The physical and psychological long‐term and late effects among adult survivors of pediatric and adult cancers are described and the emergence of public health initiatives and large‐scale research activities that address the issues of long-term cancer survivorship are discussed.
Abstract: The number of long-term cancer survivors (> or =5 years after diagnosis) in the U.S. continues to rise, with more than 10 million Americans now living with a history of cancer. Along with such growth has come increasing attention to the continued health problems and needs of this population. Many cancer survivors return to normal functioning after the completion of treatment and are able to live relatively symptom-free lives. However, cancer and its treatment can also result in a wide range of physical and psychological problems that do not recede with time. Some of these problems emerge during or after cancer treatment and persist in a chronic, long-term manner. Other problems may not appear until months or even years later. Regardless of when they present, long-term and late effects of cancer can have a negative effect on cancer survivors' quality of life. This article describes the physical and psychological long-term and late effects among adult survivors of pediatric and adult cancers. The focus is on the prevalence and correlates of long-term and late effects as well as the associated deficits in physical and emotional functioning. In addition, the emergence of public health initiatives and large-scale research activities that address the issues of long-term cancer survivorship are discussed. Although additional research is needed to fully understand and document the long-term and late effects of cancer, important lessons can be learned from existing knowledge. Increased awareness of these issues is a key component in the development of follow-up care plans that may allow for adequate surveillance, prevention, and the management of long-term and late effects of cancer.
TL;DR: It is proposed that N. benthamiana is well situated to become a premier plant cell biology model, particularly for the virology community, who as a group were the first to recognize the potential of this unique Australian native.
Abstract: Nicotiana benthamiana is the most widely used experimental host in plant virology, due mainly to the large number of diverse plant viruses that can successfully infect it. Additionally, N. benthamiana is susceptible to a wide variety of other plant-pathogenic agents (such as bacteria, oomycetes, fungi, and so on), making this species a cornerstone of host-pathogen research, particularly in the context of innate immunity and defense signaling. Moreover, because it can be genetically transformed and regenerated with good efficiency and is amenable to facile methods for virus-induced gene silencing or transient protein expression, N. benthamiana is rapidly gaining popularity in plant biology, particularly in studies requiring protein localization, interaction, or plant-based systems for protein expression and purification. Paradoxically, despite being an indispensable research model, little is known about the origins, genetic variation, or ecology of the N. benthamiana accessions currently used by the research community. In addition to addressing these latter topics, the purpose of this review is to provide information regarding sources for tools and reagents that can be used to support research in N. benthamiana. Finally, we propose that N. benthamiana is well situated to become a premier plant cell biology model, particularly for the virology community, who as a group were the first to recognize the potential of this unique Australian native.
TL;DR: Clinical trials have confirmed that certain lipoproteins and the renin–angiotensin–aldosterone system are important in the pathogenesis of atherosclerotic cardiovascular disease, and that interventions targeted towards these are beneficial.
Abstract: Atherosclerosis is characterized by the thickening of the arterial wall and is the primary cause of coronary artery disease and cerebrovascular disease, two of the most common causes of illness and death worldwide. Clinical trials have confirmed that certain lipoproteins and the renin-angiotensin-aldosterone system are important in the pathogenesis of atherosclerotic cardiovascular disease, and that interventions targeted towards these are beneficial. Furthermore, efforts to understand how risk factors such as high blood pressure, dysregulated blood lipids and diabetes contribute to atherosclerotic disease, as well as to understand the molecular pathogenesis of atherosclerotic plaques, are leading to new targets for therapy.
TL;DR: In this article, the authors investigated the asymptotic properties of quasi-maximum likelihood estimators for spatial dynamic panel data with the same number of individuals and the number of time periods.
TL;DR: Remote controlled pulsatile drug release was characterized for different drugs as well as for different ON-OFF durations of the AMF.
TL;DR: A comprehensive assessment of the multiple symptoms domains associated with fibromyalgia and the impact of Fibromyalgia on multidimensional aspects of function should be a routine part of the care of fibromyalgic patients.
TL;DR: By connecting device fabrication to molecular design, it is demonstrated that rapid film processing under ambient room conditions and high performance are not mutually exclusive.
Abstract: The use of organic materials presents a tremendous opportunity to significantly impact the functionality and pervasiveness of large-area electronics. Commercialization of this technology requires reduction in manufacturing costs by exploiting inexpensive low-temperature deposition and patterning techniques, which typically lead to lower device performance. We report a low-cost approach to control the microstructure of solution-cast acene-based organic thin films through modification of interfacial chemistry. Chemically and selectively tailoring the source/drain contact interface is a novel route to initiating the crystallization of soluble organic semiconductors, leading to the growth on opposing contacts of crystalline films that extend into the transistor channel. This selective crystallization enables us to fabricate high-performance organic thin-film transistors and circuits, and to deterministically study the influence of the microstructure on the device characteristics. By connecting device fabrication to molecular design, we demonstrate that rapid film processing under ambient room conditions and high performance are not mutually exclusive.
TL;DR: EGFR/HER2 may mediate tamoxifen resistance in ER-positive breast cancer despite continued suppression of ER genomic function by tamox ifen, providing a rationale to combine HER inhibitors with tamoxIFen in clinical studies, even in tumors that do not initially overexpress EGFR/ HER2.
Abstract: Not all breast cancers respond to tamoxifen, and many develop resistance despite initial benefit. We used an in vivo model of estrogen receptor (ER)-positive breast cancer (MCF-7 xenografts) to investigate mechanisms of this resistance and develop strategies to circumvent it. Epidermal growth factor receptor (EGFR) and HER2, which were barely detected in control estrogen-treated tumors, increased slightly with tamoxifen and were markedly increased when tumors became resistant. Gefitinib, which inhibits EGFR/HER2, improved the antitumor effect of tamoxifen and delayed acquired resistance, but had no effect on estrogen-stimulated growth. Phosphorylated levels of p42/44 and p38 mitogen-activated protein kinases (both downstream of EGFR/HER2) were increased in the tamoxifen-resistant tumors and were suppressed by gefitinib. There was no apparent increase in phosphorylated AKT (also downstream of EGFR/HER2) in resistant tumors, but it was nonetheless suppressed by gefitinib. Phosphorylated insulin-like growth factor-IR (IGF-IR), which can interact with both EGFR and membrane ER, was elevated in the tamoxifen-resistant tumors compared with the sensitive group. However, ER-regulated gene products, including total IGF-IR itself and progesterone receptor, remained suppressed even at the time of acquired resistance. Tamoxifen's antagonism of classic ER genomic function was retained in these resistant tumors and even in tumors that overexpress HER2 (MCF-7 HER2/18) and are de novo tamoxifen-resistant. In conclusion, EGFR/HER2 may mediate tamoxifen resistance in ER-positive breast cancer despite continued suppression of ER genomic function by tamoxifen. IGF-IR expression remains dependent on ER but is activated in the tamoxifen-resistant tumors. This study provides a rationale to combine HER inhibitors with tamoxifen in clinical studies, even in tumors that do not initially overexpress EGFR/HER2.
TL;DR: In healthy older adults, 10 days of bed rest results in a substantial loss of lower extremity strength, power, and aerobic capacity, and a reduction in physical activity, but has no effect on physical performance.
Abstract: Background. Many older individuals decline functionally during hospitalization, and the deleterious consequences of bed rest may be one cause. This study reports on the effect of 10 days of bed rest on multiple functional parameters in healthy older adults. Methods. Healthy older men and women (n ¼ 11, 67 6 5 years old) remained on bed rest for 10 days continuously, and consumed a eucaloric diet providing the Recommended Dietary Allowance for protein. Measures of lower extremity strength and power, aerobic capacity and physical performance, as well as physical activity were performed before and after bed rest. Results. All measures of lower extremity strength were significantly lower after bed rest including isotonic knee extensor strength (� 13.2 6 4.1%, p ¼ .004) and stair-climbing power (� 14 6 4.1%, p ¼ .01). Maximal aerobic capacity was 12% lower after bed rest (p ¼ .04), whereas measures of physical performance (Short Physical Performance Battery, and a five-item physical performance test) were not significantly different. Voluntary physical activity decreased after bed rest, and the percentage of time spent inactive increased (7.6 6 1.8%, p ¼ .004). There were no medical complications. Conclusions. In healthy older adults, 10 days of bed rest results in a substantial loss of lower extremity strength, power, and aerobic capacity, and a reduction in physical activity, but has no effect on physical performance. Identification of interventions to maintain muscle function during hospitalization or periods of bed rest in older adults should be a high priority.
TL;DR: In vivo characterization of differentially-expressed products in gonads demonstrates that Angiotensin Converting Enzyme varies between Wolbachia infected and uninfected flies and that the variation occurs in a sex-specific manner, which supports the use of Wolbachian infected cell cultures as an appropriate model for predicting in vivo host/Wolbachia interactions.
Abstract: Intracellular Wolbachia bacteria are obligate, maternally-inherited, endosymbionts found frequently in insects and other invertebrates. The success of Wolbachia can be attributed in part to an ability to alter host reproduction via mechanisms including cytoplasmic incompatibility (CI), parthenogenesis, feminization and male killing. Despite substantial scientific effort, the molecular mechanisms underlying the Wolbachia/host interaction are unknown. Here, an in vitro Wolbachia infection was generated in the Drosophila S2 cell line, and transcription profiles of infected and uninfected cells were compared by microarray. Differentially-expressed patterns related to reproduction, immune response and heat stress response are observed, including multiple genes that have been previously reported to be involved in the Wolbachia/host interaction. Subsequent in vivo characterization of differentially-expressed products in gonads demonstrates that Angiotensin Converting Enzyme (Ance) varies between Wolbachia infected and uninfected flies and that the variation occurs in a sex-specific manner. Consistent with expectations for the conserved CI mechanism, the observed Ance expression pattern is repeatable in different Drosophila species and with different Wolbachia types. To examine Ance involvement in the CI phenotype, compatible and incompatible crosses of Ance mutant flies were conducted. Significant differences are observed in the egg hatch rate resulting from incompatible crosses, providing support for additional experiments examining for an interaction of Ance with the CI mechanism. Wolbachia infection is shown to affect the expression of multiple host genes, including Ance. Evidence for potential Ance involvement in the CI mechanism is described, including the prior report of Ance in spermatid differentiation, Wolbachia-induced sex-specific effects on Ance expression and an Ance mutation effect on CI levels. The results support the use of Wolbachia infected cell cultures as an appropriate model for predicting in vivo host/Wolbachia interactions.