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Find video protocols related to scientific articles indexed in Pubmed.
Training and certification in dialysis access.
J Vasc Access
PUBLISHED: 10-09-2014
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Decreasing and eliminating the gaps in knowledge, skills, and effective communication are the mainstays for a successful dialysis access training program curriculum and at the core of the human factors training philosophy. Many of these skills can be learned in the simulation environment. Education and training will reduce gaps in knowledge and technical skills, before exposing patients to procedure-related risk. For dialysis access, a reliable workplace environment depends upon a culture where safety and accountability are balanced to recognize the human contribution to success or failure in the complex care of patients with end-stage renal disease. Rigorous testing and certification adds value to the participants and validates the training program.
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The clinical use of a P63/cytokeratin7/18/cytokeratin5/14 antibody cocktail in diagnostic breast pathology.
Ann Diagn Pathol
PUBLISHED: 07-17-2014
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An antibody cocktail directed against p63, cytokeratin (CK)5/14, and CK7/18 is reported to be useful in distinguishing noninvasive from invasive breast lesions and for the characterization of intraductal epithelial proliferations. However, limited studies evaluate its use in clinical practice. A retrospective review of breast material at a university medical center identified cases that were immunostained with the above antibody cocktail. Additional p63 immunostaining alone was performed to further determine the utility of the antibody cocktail in the evaluation of invasion. Of 50 breast cases identified, the antibody cocktail was used to confirm or exclude invasion in 44 (88%). Twenty-two (50%) of these had easily identifiable p63/CK5/14-positive myoepithelial cells, whereas the remainder lacked such staining, confirming the diagnosis of invasive carcinoma. In 27 cases with available diagnostic material for additional p63 immunostaining, the cocktail better highlighted myoepithelial cells by staining nuclei and cytoplasm. Easier identification of invasion was also facilitated by CK7/18 expression in invasive foci, especially those composed of single cells. Ten cases were immunostained to help determine the nature of an intraductal proliferation. The cocktail demonstrated a mosaic staining pattern of both CK7/18- and CK5/14-positive epithelial cells in 3 (30%) cases consistent with usual hyperplasia; homogenous CK7/18 expression in the remaining cases supported the diagnosis of atypical ductal hyperplasia or carcinoma in situ. In summary, the p63/CK7/18/CK5/14 cocktail stain appears to be a useful tool in diagnostic breast pathology, in the evaluation of possible invasion, particularly in the setting of minute foci of invasion as well as in epithelial proliferations.
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Saturation diving; physiology and pathophysiology.
Compr Physiol
PUBLISHED: 06-20-2014
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In saturation diving, divers stay under pressure until most of their tissues are saturated with breathing gas. Divers spend a long time in isolation exposed to increased partial pressure of oxygen, potentially toxic gases, bacteria, and bubble formation during decompression combined with shift work and long periods of relative inactivity. Hyperoxia may lead to the production of reactive oxygen species (ROS) that interact with cell structures, causing damage to proteins, lipids, and nucleic acid. Vascular gas-bubble formation and hyperoxia may lead to dysfunction of the endothelium. The antioxidant status of the diver is an important mechanism in the protection against injury and is influenced both by diet and genetic factors. The factors mentioned above may lead to production of heat shock proteins (HSP) that also may have a negative effect on endothelial function. On the other hand, there is a great deal of evidence that HSPs may also have a "conditioning" effect, thus protecting against injury. As people age, their ability to produce antioxidants decreases. We do not currently know the capacity for antioxidant defense, but it is reasonable to assume that it has a limit. Many studies have linked ROS to disease states such as cancer, insulin resistance, diabetes mellitus, cardiovascular diseases, and atherosclerosis as well as to old age. However, ROS are also involved in a number of protective mechanisms, for instance immune defense, antibacterial action, vascular tone, and signal transduction. Low-grade oxidative stress can increase antioxidant production. While under pressure, divers change depth frequently. After such changes and at the end of the dive, divers must follow procedures to decompress safely. Decompression sickness (DCS) used to be one of the major causes of injury in saturation diving. Improved decompression procedures have significantly reduced the number of reported incidents; however, data indicate considerable underreporting of injuries. Furthermore, divers who are required to return to the surface quickly are under higher risk of serious injury as no adequate decompression procedures for such situations are available. Decompression also leads to the production of endothelial microparticles that may reduce endothelial function. As good endothelial function is a documented indicator of health that can be influenced by regular exercise, regular physical exercise is recommended for saturation divers. Nowadays, saturation diving is a reasonably safe and well controlled method for working under water. Until now, no long-term impact on health due to diving has been documented. However, we still have limited knowledge about the pathophysiologic mechanisms involved. In particular we know little about the effect of long exposure to hyperoxia and microparticles on the endothelium.
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Measurement of the temporal transferability of indoxacarb to cotton gloves from spot-on treated dogs.
J. Toxicol. Environ. Health Part A
PUBLISHED: 05-03-2014
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The objectives of the studies reported herein were to (1) determine the minimum number of petting simulations required to load the maximum amount of test substance (indoxacarb) residue onto cotton gloves (the sampling medium) from spot-on treated dogs; and (2) using the number of petting simulations that resulted in maximal transfer, to conduct a second study that measured amount of residue dislodged via petting a dog as a function of the time interval after application. Maximal percent transfer of indoxacarb from spot-on treated dogs occurred after 10 repetitive petting simulations (consisting of 3 directional pet strokes each) and was approximately 1-2% of amount applied. Temporal measurements of mean indoxacarb transferability followed an exponential decay function, beginning at approximately 2% transfer on the day of application, and declining to 0.08% by d 30 post treatment.
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EARLY FLOWERING3 Regulates Flowering in Spring Barley by Mediating Gibberellin Production and FLOWERING LOCUS T Expression.
Plant Cell
PUBLISHED: 04-29-2014
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EARLY FLOWERING3 (ELF3) is a circadian clock gene that contributes to photoperiod-dependent flowering in plants, with loss-of-function mutants in barley (Hordeum vulgare), legumes, and Arabidopsis thaliana flowering early under noninductive short-day (SD) photoperiods. The barley elf3 mutant displays increased expression of FLOWERING LOCUS T1 (FT1); however, it remains unclear whether this is the only factor responsible for the early flowering phenotype. We show that the early flowering and vegetative growth phenotypes of the barley elf3 mutant are strongly dependent on gibberellin (GA) biosynthesis. Expression of the central GA biosynthesis gene, GA20oxidase2, and production of the bioactive GA, GA1, were significantly increased in elf3 leaves under SDs, relative to the wild type. Inhibition of GA biosynthesis suppressed the early flowering of elf3 under SDs independently of FT1 and was associated with altered expression of floral identity genes at the developing apex. GA is also required for normal flowering of spring barley under inductive photoperiods, with chemical and genetic attenuation of the GA biosynthesis and signaling pathways suppressing inflorescence development under long-day conditions. These findings illustrate that GA is an important floral promoting signal in barley and that ELF3 suppresses flowering under noninductive photoperiods by blocking GA production and FT1 expression.
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Sugar demand, not auxin, is the initial regulator of apical dominance.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 04-07-2014
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For almost a century the plant hormone auxin has been central to theories on apical dominance, whereby the growing shoot tip suppresses the growth of the axillary buds below. According to the classic model, the auxin indole-3-acetic acid is produced in the shoot tip and transported down the stem, where it inhibits bud growth. We report here that the initiation of bud growth after shoot tip loss cannot be dependent on apical auxin supply because we observe bud release up to 24 h before changes in auxin content in the adjacent stem. After the loss of the shoot tip, sugars are rapidly redistributed over large distances and accumulate in axillary buds within a timeframe that correlates with bud release. Moreover, artificially increasing sucrose levels in plants represses the expression of BRANCHED1 (BRC1), the key transcriptional regulator responsible for maintaining bud dormancy, and results in rapid bud release. An enhancement in sugar supply is both necessary and sufficient for suppressed buds to be released from apical dominance. Our data support a theory of apical dominance whereby the shoot tip's strong demand for sugars inhibits axillary bud outgrowth by limiting the amount of sugar translocated to those buds.
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TRACKING CHANGES IN STATES OF CONTRACEPTIVE USE OVER TIME IN SUB-SAHARAN AFRICA THROUGH COHORT AND PERIOD ANALYSES.
J Biosoc Sci
PUBLISHED: 03-29-2014
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Summary It is difficult to gauge the success of programmatic efforts to reduce unmet need for contraception without knowing whether individual women have had their need met and adopted contraception. However, the number of true longitudinal datasets tracking the transition of panels of individual women in and out of states of contraceptive use is limited. This study analyses changes in contraceptive use states using Demographic and Health Survey data for 22 sub-Saharan African countries. A cohort approach, tracking representative samples of five-year age groups longitudinally across surveys, as well as period-based techniques, are applied to indicate whether new users of contraception have been drawn from women who previously had no need and/or those who had unmet need for family planning. The results suggest that a greater proportion of increases in contraceptive use in recent years can be attributed to decreases in the percentage of women with no need, especially among younger women, than to decreases in the proportion with unmet need.
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Queen Anne (1665-1714) and her health.
J Med Biogr
PUBLISHED: 03-25-2014
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The contemporary records of Queen Anne's health and disease are reviewed, including the strange diagnoses made and the treatments prescribed. A correct diagnosis is suggested.
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Evaluation of the interpretation of serial ultrasound examinations in the diagnosis of deep venous thrombosis in children: a retrospective cohort study.
Can Assoc Radiol J
PUBLISHED: 03-17-2014
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To assess ultrasound intrascan variability and the potential error rate of serial ultrasounds in the diagnosis of deep venous thrombosis in children.
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The shifting paradigms of auxin biosynthesis.
Trends Plant Sci.
PUBLISHED: 02-14-2014
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Auxins are an important group of hormones found in all land plants and several soil-dwelling microbes. Although auxin was the first phytohormone identified, its biosynthesis remained unclear until recently. In the past few years, our understanding of auxin biosynthesis has im-proved dramatically, to the stage where many believe there is a single predominant pathway in Arabidopsis (Arabidopsis thaliana L.). However, there is still uncertainty over the applicability of these findings to other plant species. Indeed, it appears that in certain organs of some species, other pathways can operate. Here we review the key advances that have led to our current understanding of auxin biosynthesis and its many pro-posed pathways.
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MIDER: network inference with mutual information distance and entropy reduction.
PLoS ONE
PUBLISHED: 01-01-2014
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The prediction of links among variables from a given dataset is a task referred to as network inference or reverse engineering. It is an open problem in bioinformatics and systems biology, as well as in other areas of science. Information theory, which uses concepts such as mutual information, provides a rigorous framework for addressing it. While a number of information-theoretic methods are already available, most of them focus on a particular type of problem, introducing assumptions that limit their generality. Furthermore, many of these methods lack a publicly available implementation. Here we present MIDER, a method for inferring network structures with information theoretic concepts. It consists of two steps: first, it provides a representation of the network in which the distance among nodes indicates their statistical closeness. Second, it refines the prediction of the existing links to distinguish between direct and indirect interactions and to assign directionality. The method accepts as input time-series data related to some quantitative features of the network nodes (such as e.g. concentrations, if the nodes are chemical species). It takes into account time delays between variables, and allows choosing among several definitions and normalizations of mutual information. It is general purpose: it may be applied to any type of network, cellular or otherwise. A Matlab implementation including source code and data is freely available (http://www.iim.csic.es/~gingproc/mider.html). The performance of MIDER has been evaluated on seven different benchmark problems that cover the main types of cellular networks, including metabolic, gene regulatory, and signaling. Comparisons with state of the art information-theoretic methods have demonstrated the competitive performance of MIDER, as well as its versatility. Its use does not demand any a priori knowledge from the user; the default settings and the adaptive nature of the method provide good results for a wide range of problems without requiring tuning.
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Strigolactones stimulate internode elongation independently of gibberellins.
Plant Physiol.
PUBLISHED: 08-13-2013
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Strigolactone (SL) mutants in diverse species show reduced stature in addition to their extensive branching. Here, we show that this dwarfism in pea (Pisum sativum) is not attributable to the strong branching of the mutants. The continuous supply of the synthetic SL GR24 via the root system using hydroponics can restore internode length of the SL-deficient rms1 mutant but not of the SL-response rms4 mutant, indicating that SLs stimulate internode elongation via RMS4. Cytological analysis of internode epidermal cells indicates that SLs control cell number but not cell length, suggesting that SL may affect stem elongation by stimulating cell division. Consequently, SLs can repress (in axillary buds) or promote (in the stem) cell division in a tissue-dependent manner. Because gibberellins (GAs) increase internode length by affecting both cell division and cell length, we tested if SLs stimulate internode elongation by affecting GA metabolism or signaling. Genetic analyses using SL-deficient and GA-deficient or DELLA-deficient double mutants, together with molecular and physiological approaches, suggest that SLs act independently from GAs to stimulate internode elongation.
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Post-traumatic basal ganglia haemorrhage in a child with primary central nervous system lymphoma.
BMJ Case Rep
PUBLISHED: 08-02-2013
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Primary central nervous system lymphoma (PCNSL) is a rare tumour of childhood with 15-20 cases reported yearly in North America. We present a case of a 13-year-old boy diagnosed with PCNSL who presented more than one-and-a-half years post-treatment with high dose cytosine arabinoside and methotrexate with a right-sided basal ganglia haemorrhage on MRI following a concussion while playing organised football against medical advice. There was no evidence of an underlying vascular malformation or recurrent disease by MRI, cerebrospinal fluid analysis or positron emission tomography computed tomography (PET-CT). However, 6 months post-injury he presented with asymptomatic disease recurrence of the frontal lobe. Our case reports an unusual MRI pattern of post-traumatic injury in a child previously treated for PCNSL that would support a recommendation for the avoidance of contact sports in this population.
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Revised methods for estimating potential reentry exposure associated with indoor crack and crevice and perimeter application.
J. Toxicol. Environ. Health Part A
PUBLISHED: 06-12-2013
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Surface deposition of insecticides applied as indoor residential foggers, baseboard or perimeter sprays, spot sprays, and crack-and-crevice (C&C) sprays represent pathways of unintentional, postapplication exposure for children and adults. Estimation of the magnitude of this exposure following an application event is associated with uncertainty due to many factors, including (1) surface residue deposition and distribution, (2) access to and the nature of contact with treated surfaces based on time-activity patterns of residents, and (3) the role of residue removal mechanisms such as cleaning treated surfaces, pesticide degradation or redistribution, and hand washing and bathing following contact. A comparative spatial deposition study was conducted involving broadcast, perimeter, and C&C application methods. Residues measured using a spatial grid of deposition dosimeters on floor surfaces demonstrated significantly lower residue concentrations in readily accessible areas following C&C and perimeter applications, versus broadcast treatment. Analyses of other monitoring studies support this finding. The implications of these findings are discussed for both screening-level and higher tier probabilistic postapplication, residential exposure assessment. The U.S. Environmental Protection Agency (EPA) current guidance on interpretation of deposition following C&C application is supported by data in this study and others that indicate a ratio of 10:1 for deposition for broadcast versus C&C application. However, the perimeter deposition data are quite similar to C&C deposition and do not support a 70/30 default relative to broadcast recommended by the U.S. EPA (2012).
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Vitamin B12 deficiency presenting as acute ataxia.
BMJ Case Rep
PUBLISHED: 03-29-2013
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A previously healthy 7-year-old Caucasian boy was hospitalised for evaluation of acute ataxia and failure to thrive, initially suspicious for an intracranial mass. Weight and body mass index were below the third percentile and he demonstrated loss of joint position and vibratory sense on examination. Laboratory studies revealed megaloblastic anaemia while an initial MRI of the brain showed no evidence of mass lesions or other abnormalities. A dietary history revealed the child subscribed to a restrictive vegan diet with little to no intake of animal products or other fortified foods. The child was diagnosed with presumed vitamin B12 deficiency and was treated with intramuscular B12 injections. Neurological symptoms resolved promptly within several days after starting therapy. This case underlines the importance of assessing nutritional status in the evaluation of neurological dysfunction in the pediatric patient.
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Plant hormones in arbuscular mycorrhizal symbioses: an emerging role for gibberellins.
Ann. Bot.
PUBLISHED: 03-18-2013
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Arbuscular mycorrhizal symbioses are important for nutrient acquisition in >80 % of terrestrial plants. Recently there have been major breakthroughs in understanding the signals that regulate colonization by the fungus, but the roles of the known plant hormones are still emerging. Here our understanding of the roles of abscisic acid, ethylene, auxin, strigolactones, salicylic acid and jasmonic acid is discussed, and the roles of gibberellins and brassinosteroids examined.
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Effects of tyrosine kinase inhibitors on rat isolated heart function and protein biomarkers indicative of toxicity.
J Pharmacol Toxicol Methods
PUBLISHED: 02-15-2013
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Cardiac toxicity, manifested as diminished contractility, ischemic heart disease, and heart failure is a major issue in drug safety. Concerns revolve around targeted drugs (TKIs) where contractility effects were not anticipated. The ability to predict cardiac toxicity early would help to de-risk drugs in development and prepare physicians to manage risk in the clinic. Issues with current preclinical studies include insufficient testing with informative, translatable models, and predictive biomarkers. The isolated heart model is amenable to multiple assessments which can be combined with current technologies to assess toxicity on a multi-scale level.
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Role of carbamazepine in the symptomatic treatment of subacute sclerosing panencephalitis: a case report and review of the literature.
Case Rep Neurol Med
PUBLISHED: 01-22-2013
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We describe the clinical presentation and clinical course of subacute sclerosing panencephalitis in a 13-year-old previously healthy boy who recently immigrated to the United States from Iraq. He presented with macular retinopathy, followed by progressive myoclonus and encephalopathy. After extensive workup, a diagnosis of subacute sclerosing panencephalitis was suspected by the presence of period epileptiform discharges on electroencephalogram and confirmed by elevated measles titers in the cerebrospinal fluid. Combination immunomodulatory therapy with isoprinosine, ribavirin, and intra-Ommaya interferon alpha did not result in clinical improvement. Within days following the administration of carbamazepine, there was remarkable improvement in the myoclonus and he was able to ambulate independently for a period of 4 months at which time he unfortunately progressed to a vegetative state. This case highlights the importance of carbamazepine as a potential first line symptomatic treatment of subacute sclerosing panencephalitis and provides a review of the literature on the subject.
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SEPALLATA1/2-suppressed mature apples have low ethylene, high auxin and reduced transcription of ripening-related genes.
AoB Plants
PUBLISHED: 01-17-2013
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Fruit ripening is an important developmental trait in fleshy fruits, making the fruit palatable for seed dispersers. In some fruit species, there is a strong association between auxin concentrations and fruit ripening. We investigated the relationship between auxin concentrations and the onset of ethylene-related ripening in Malus × domestica (apples) at both the hormone and transcriptome levels.
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Psychological and physical correlates of musculoskeletal symptoms in male professional divers and offshore workers.
Extrem Physiol Med
PUBLISHED: 01-07-2013
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Underwater divers are more likely to complain of musculoskeletal symptoms than a control population. Accordingly, we conducted a study to determine whether musculoskeletal symptoms reflected observable physical disorder, to ascertain the relationship between symptoms and measures of mood, memory and executive function and to assess any need for future screening.
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New findings for maternal mortality age patterns: aggregated results for 38 countries.
PLoS ONE
PUBLISHED: 01-01-2013
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With recent results showing a global decline in overall maternal mortality during the last two decades and with the target date for achieving the Millennium Development Goals only four years away, the question of how to continue or even accelerate the decline has become more pressing. By knowing where the risk is highest as well as where the numbers of deaths are greatest, it may be possible to re-direct resources and fine-tune strategies for greater effectiveness in efforts to reduce maternal mortality.
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Trends in national family planning programs, 1999, 2004 and 2009.
Int Perspect Sex Reprod Health
PUBLISHED: 10-13-2011
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National family planning programs in the developing world vary greatly in strength and coverage, and in the nature of their outreach. Periodic measures of their types and levels of effort have been conducted since 1972.
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Mendels genes: toward a full molecular characterization.
Genetics
PUBLISHED: 09-13-2011
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The discipline of classical genetics is founded on the hereditary behavior of the seven genes studied by Gregor Mendel. The advent of molecular techniques has unveiled much about the identity of these genes. To date, four genes have been sequenced: A (flower color), LE (stem length), I (cotyledon color), and R (seed shape). Two of the other three genes, GP (pod color) and FA (fasciation), are amenable to candidate gene approaches on the basis of their function, linkage relationships, and synteny between the pea and Medicago genomes. However, even the gene (locus) identity is not known for certain for the seventh character, the pod form, although it is probably V. While the nature of the mutations used by Mendel cannot be determined with certainty, on the basis of the varieties available in Europe in the 1850s, we can speculate on their nature. It turns out that these mutations are attributable to a range of causes-from simple base substitutions and changes to splice sites to the insertion of a transposon-like element. These findings provide a fascinating connection between Mendelian genetics and molecular biology that can be used very effectively in teaching new generations of geneticists. Mendels characters also provide novel insights into the nature of the genes responsible for characteristics of agronomic and consumer importance.
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Use of a generalized fisher equation for global optimization in chemical kinetics.
J Phys Chem A
PUBLISHED: 07-14-2011
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A new approach for parameter estimation in chemical kinetics has been recently proposed (Ross et al. Proc. Natl. Acad. Sci. U.S.A. 2010, 107, 12777). It makes use of an optimization criterion based on a Generalized Fisher Equation (GFE). Its utility has been demonstrated with two reaction mechanisms, the chlorite-iodide and Oregonator, which are computationally stiff systems. In this Article, the performance of the GFE-based algorithm is compared to that obtained from minimization of the squared distances between the observed and predicted concentrations obtained by solving the corresponding initial value problem (we call this latter approach "traditional" for simplicity). Comparison of the proposed GFE-based optimization method with the "traditional" one has revealed their differences in performance. This difference can be seen as a trade-off between speed (which favors GFE) and accuracy (which favors the traditional method). The chlorite-iodide and Oregonator systems are again chosen as case studies. An identifiability analysis is performed for both of them, followed by an optimal experimental design based on the Fisher Information Matrix (FIM). This allows to identify and overcome most of the previously encountered identifiability issues, improving the estimation accuracy. With the new data, obtained from optimally designed experiments, it is now possible to estimate effectively more parameters than with the previous data. This result, which holds for both GFE-based and traditional methods, stresses the importance of an appropriate experimental design. Finally, a new hybrid method that combines advantages from the GFE and traditional approaches is presented.
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D-amino acid oxidase activity is inhibited by an interaction with bassoon protein at the presynaptic active zone.
J. Biol. Chem.
PUBLISHED: 06-23-2011
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Schizophrenia is a highly heritable neuropsychiatric disorder affecting ?1% of the worlds population. Linkage and association studies have identified multiple candidate schizophrenia susceptibility genes whose functions converge on the glutamatergic neurotransmitter system. One such susceptibility gene encoding D-amino acid oxidase (DAO), an enzyme that metabolizes the NMDA receptor (NMDAR) co-agonist D-serine, has the potential to modulate NMDAR function in the context of schizophrenia. To further investigate its cellular regulation, we sought to identify DAO-interacting proteins that participate in its functional regulation in rat cerebellum, where DAO expression is especially high. Immunoprecipitation with DAO-specific antibodies and subsequent mass spectrometric analysis of co-precipitated proteins yielded 24 putative DAO-interacting proteins. The most robust interactions occurred with known components of the presynaptic active zone, such as bassoon (BSN) and piccolo (PCLO). The interaction of DAO with BSN was confirmed through co-immunoprecipitation assays using DAO- and BSN-specific antibodies. Moreover, DAO and BSN colocalized with one another in cultured cerebellar granule cells and in synaptic junction membrane protein fractions derived from rat cerebellum. The functional consequences of this interaction were studied through enzyme assay experiments, where DAO enzymatic activity was significantly inhibited as a result of its interaction with BSN. Taking these results together, we hypothesize that synaptic D-serine concentrations may be under tight regulation by a BSN-DAO complex. We therefore predict that this mechanism plays a role in the modulation of glutamatergic signaling through NMDARs. It also furthers our understanding of the biology underlying this potential therapeutic entry point for schizophrenia and other psychiatric disorders.
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Concurrent 2,4-D and triclopyr biomonitoring of backpack applicators, mixer/loader and field supervisor in forestry.
J Environ Sci Health B
PUBLISHED: 04-19-2011
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Two herbicides, 2,4-D and triclopyr esters (application ratio 1.6:1 acid equivalents) were applied as a tank mix by a crew of 8 backpack sprayer applicators, a mixer/loader, and a field supervisor. The crew was employed in a conifer release program in northern California during the summer of 2002. Biomonitoring (urine, 24 h) utilized 2,4-D and triclopyr (a.e.) as rapidly excreted exposure biomarkers. The absorbed dosages of 2,4-D and triclopyr were calculated based upon cotton whole body suits and biomonitoring. Dosages based upon accumulation of the herbicides on body suits averaged 42.6 ?g (a.e.) 2,4-D/kg-d and 8.0 ?g (a.e.) triclopyr/kg-d. Six consecutive days of concurrent urine collections showed that backpack applicators excreted an average of 11.0 ?g (a.e.) 2,4-D/kg-d and 18.9 ?g (a.e.) triclopyr/kg-d. Estimates based upon curve fitting were 17.1 and 29.3 ?g (a.e.)/kg-d, respectively. Results suggest that passive dosimetry for 2,4-D consistently overestimated the dosage measured using biomonitoring by a factor of 2-3 fold, while for triclopyr, passive dosimetry underestimated the absorbed dose based on biomonitoring by a factor of 2-4 fold.
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Group I mGluR-regulated translation of the neuronal glutamate transporter, excitatory amino acid carrier 1.
J. Neurochem.
PUBLISHED: 04-11-2011
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Recently, we demonstrated that mRNA for the neuronal glutamate transporter, excitatory amino acid carrier 1 (EAAC1), is found in dendrites of hippocampal neurons in culture and in dendrites of hippocampal pyramidal cells after pilocarpine-induced status epilepticus (SE). We also showed that SE increased the levels of EAAC1 mRNA ~15-fold in synaptoneurosomes. In this study, the effects of SE on the distribution EAAC1 protein in hippocampus were examined. In addition, the effects of Group 1 mGluR receptor activation on the levels of EAAC1 protein were examined in synaptoneurosomes prepared from sham control animals and from animals that experience pilocarpine-induced SE. We find that EAAC1 immunoreactivity increases in pyramidal cells of the hippocampus after 3 h of SE. In addition, the group I mGluR agonist, (S)-3,5-dihydroxyphenylglycine (DHPG), caused an increase in EAAC1 protein levels in hippocampal synaptoneurosomes; this effect of DHPG was much larger (~3- to 5-fold) after 3 h of SE. The DHPG-induced increases in EAAC1 protein were blocked by two different inhibitors of translation but not by inhibitors of transcription. mGluR1 or mGluR5 antagonists completely blocked the DHPG-induced increases in EAAC1 protein. DHPG also increased the levels of glutamate receptor 2/3 protein, but this effect was not altered by SE. The DHPG-induced increase in EAAC1 protein was blocked by an inhibitor of the mammalian target of rapamycin or an inhibitor of extracellular signal-regulated kinase. These studies provide the first evidence EAAC1 translation can be regulated, and they show that regulated translation of EAAC1 is up-regulated after SE.
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Canalization effect in the coagulation cascade and the interindividual variability of oral anticoagulant response. A simulation study.
Theor Biol Med Model
PUBLISHED: 03-21-2011
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Increasing the predictability and reducing the rate of side effects of oral anticoagulant treatment (OAT) requires further clarification of the cause of about 50% of the interindividual variability of OAT response that is currently unaccounted for. We explore numerically the hypothesis that the effect of the interindividual expression variability of coagulation proteins, which does not usually result in a variability of the coagulation times in untreated subjects, is unmasked by OAT.
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Reassessing the role of YUCCAs in auxin biosynthesis.
Plant Signal Behav
PUBLISHED: 03-01-2011
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It is remarkable that although auxin was the first growth-promoting plant hormone to be discovered, and although more researchers work on this hormone than on any other, we cannot be definitive about the pathways of auxin synthesis in plants. In 2001, there appeared to be a dramatic development in this field, with the announcement of a new gene, and a new intermediate, purportedly from the tryptamine pathway for converting tryptophan to the main endogenous auxin, indole-3-acetic acid (IAA). Recently, however, we presented evidence challenging the original and subsequent identifications of the intermediate concerned.
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Auxin acts independently of DELLA proteins in regulating gibberellin levels.
Plant Signal Behav
PUBLISHED: 03-01-2011
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Shoot elongation is a vital process for plant development and productivity, in both ecological and economic contexts. Auxin and bioactive gibberellins (GAs), such as GA1, play critical roles in the control of elongation, along with environmental and endogenous factors, including other hormones such as the brassinosteroids. The effect of auxins, such as indole-3-acetic acid (IAA), is at least in part mediated by its effect on GA metabolism, since auxin up-regulates biosynthesis genes such as GA 3-oxidase and GA 20-oxidase and down regulates GA catabolism genes such as GA 2-oxidases, leading to elevated levels of bioactive GA 1. In our recent paper, we have provided evidence that this action of IAA is largely independent of DELLA proteins, the negative regulators of GA action, since the auxin effects are still present in the DELLA-deficient la cry-s genotype of pea. This was a crucial issue to resolve, since like auxin, the DELLAs also promote GA 1 synthesis and inhibit its deactivation. DELLAs are deactivated by GA, and thereby mediate a feedback system by which bioactive GA regulates its own level. However, our recent results, in themselves, do not show the generality of the auxin-GA relationship across species and phylogenetic groups or across different tissue types and responses. Further, they do not touch on the ecological benefits of the auxin-GA interaction. These issues are discussed below as well as the need for the development of suitable experimental systems to allow this process to be examined.
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Complex pharmacokinetics of a humanized antibody against human amyloid beta peptide, anti-abeta Ab2, in nonclinical species.
Pharm. Res.
PUBLISHED: 02-21-2011
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Anti-A? Ab2 (Ab2) is a humanized monoclonal antibody against amino acids 3-6 of primate (but not rodent) amyloid ? (A?) and is being evaluated for the treatment of Alzheimers disease (AD). This study was conducted to predict the human pharmacokinetics of Ab2.
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Plant hormone interactions: how complex are they?
Physiol Plant
PUBLISHED: 02-06-2011
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Models describing plant hormone interactions are often complex and web-like. Here we assess several suggested interactions within one experimental system, elongating pea internodes. Results from this system indicate that at least some suggested interactions between auxin, gibberellins (GAs), brassinosteroids (BRs), abscisic acid (ABA) and ethylene do not occur in this system or occur in the reverse direction to that suggested. Furthermore, some of the interactions are relatively weak and may be of little physiological relevance. This is especially true if plant hormones are assumed to show a log-linear response curve as many empirical results suggest. Although there is strong evidence to support some interactions between hormones (e.g. auxin stimulating ethylene and bioactive GA levels), at least some of the web-like complexities do not appear to be justified or are overstated. Simpler and more targeted models may be developed by dissecting out key interactions with major physiological effects.
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Estimation of the percutaneous absorption of permethrin in humans using the parallelogram method.
J. Toxicol. Environ. Health Part A
PUBLISHED: 01-29-2011
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The objective of this study was to develop an estimate of the percent dermal absorption of permethrin in humans to provide more accurate estimates of potential systemically absorbed dose associated with dermal exposure scenarios. Piperonyl butoxide (PBO) was used as a reference compound. The human percutaneous absorption estimate was based on the assumption that the ratio of in vivo dermal absorption (expressed as a percentage during a given time period) of permethrin through rat skin to in vitro dermal absorption through rat skin was the same as the ratio of in vivo dermal absorption in humans to in vitro dermal absorption with human skin, known as the parallelogram method. The ratio of dermal absorption by in vitro rat skin to absorption by in vitro human skin ranged from 6.7 to 15.4 (for a 24-h exposure period) with an average of 11. Data suggest in vivo human dermal absorption values for permethrin ranging from 1.4 to 3.3% when estimated based on 24-h in vivo rat values, and 2.5 to 5.7% based on 5-d in vivo rat values. The parallelogram method used to estimate dermal absorption of permethrin and PBO is supported by results from several other compounds for which in vivo and in vitro rat and human dermal absorption data exist. Collectively, these data indicate that estimating human dermal absorption from in vitro human and rat plus in vivo rat data are typically accurate within ±3-fold of the values measured in human subjects.
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Experimental methods for determining permethrin dermal absorption.
J. Toxicol. Environ. Health Part A
PUBLISHED: 01-18-2011
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The objectives of this study were to (1) determine the percutaneous absorption of radiolabeled permethrin and piperonyl butoxide (PBO) in vivo in rats and in vitro to permit a calculation of the ratio of in vitro to in vivo values, and (2) test a method of estimating in vivo human absorption. Carbon-14 labeled permethrin in ethanol solution was applied to the clipped skin of rats in vivo at doses of 2.25, 20, or 200 ?g/cm2. As a reference compound, 14C-labeled PBO in isopropanol solution was applied to rat skin in vivo at a dose of 100 ?g/cm2. All applications were washed at 24 h postapplication, and rats were sacrificed either at 24 h for permethrin or 5 d for both compounds. The radiolabel recovered from carcass, urine including cage wash, and feces was summed to determine percent absorption. For the 24-h time point, at doses of 2.25, 20, and 200 ?g/cm2 of permethrin, values of 22, 22, and 28%, respectively, were obtained for in vivo rat percutaneous absorption (n=6 per dose). For the 5-d time point, at doses of 2.25, 20, and 200 ?g/cm2 of permethrin, values of 38, 38, and 30%, respectively, were obtained for in vivo rat percutaneous absorption (n=6 per dose). The 5-d percutaneous absorption of 14C-PBO at 100 ?g/cm2 was determined to be 42% (n=6). Dose and test duration did not exert a statistically significant effect on percutaneous absorption of permethrin in the rat in vivo. For in vitro absorption determination, 14C-permethrin in ethanol solution was applied to freshly excised human skin in an in vitro test system predictive of skin absorption in humans. Twenty-four hours after application, the radiolabel recovered from dermis and receptor fluid was summed to determine percent absorption. At doses of approximately 2.25, 20, and 200 ?g/cm2 permethrin, values of 1, 3, and 2%, respectively, were obtained for percutaneous absorption (n=9 per dose). Excised human skin absorption of 14C-PBO at 100 ?g/cm2 was determined to be 7% (n=9). Excised rat skin absorptions of permethrin at 2.25, 20, and 200 ?g/cm2 were found to be 20, 18, and 24%, respectively (n=6 per dose), approximately 10-fold higher than human skin absorption. Excised rat skin absorption of PBO was also higher (35%) than the value obtained for human skin by a factor of about 5.
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Consistency between kinetics and thermodynamics: general scaling conditions for reaction rates of nonlinear chemical systems without constraints far from equilibrium.
J Phys Chem A
PUBLISHED: 12-23-2010
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We examine the problem of consistency between the kinetic and thermodynamic descriptions of reaction networks. We focus on reaction networks with linearly dependent (but generally kinetically independent) reactions for which only some of the stoichiometric vectors attached to the different reactions are linearly independent. We show that for elementary reactions without constraints preventing the system from approaching equilibrium there are general scaling relations for nonequilibrium rates, one for each linearly dependent reaction. These scaling relations express the ratios of the forward and backward rates of the linearly dependent reactions in terms of products of the ratios of the forward and backward rates of the linearly independent reactions raised to different scaling powers; the scaling powers are elements of the transformation matrix, which relates the linearly dependent stoichiometric vectors to the linearly independent stoichiometric vectors. These relations are valid for any network of elementary reactions without constraints, linear or nonlinear kinetics, far from equilibrium or close to equilibrium. We show that similar scaling relations for the reaction routes exist for networks of nonelementary reactions described by the Horiuti-Temkin theory of reaction routes where the linear dependence of the mechanistic (elementary) reactions is transferred to the overall (route) reactions. However, in this case, the scaling conditions are valid only at the steady state. General relationships between reaction rates of the two levels of description are presented. These relationships are illustrated for a specific complex reaction: radical chlorination of ethylene.
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Relationship between gibberellin, ethylene and nodulation in Pisum sativum.
New Phytol.
PUBLISHED: 11-18-2010
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• Gibberellin (GA) deficiency resulting from the na mutation in pea (Pisum sativum) causes a reduction in nodulation. Nodules that do form are aberrant, having poorly developed meristems and a lack of enlarged cells. Studies using additional GA-biosynthesis double mutants indicate that this results from severe GA deficiency of the roots rather than simply dwarf shoot stature. • Double mutants isolated from crosses between na and three supernodulating pea mutants exhibit a supernodulation phenotype, but the nodule structures are aberrant. This suggests that severely reduced GA concentrations are not entirely inhibitory to nodule initiation, but that higher GA concentrations are required for proper nodule development. • na mutants evolve more than double the amount of ethylene produced by wild-type plants, indicating that low GA concentrations can promote ethylene production. The excess ethylene may contribute to the reduced nodulation of na plants, as application of an ethylene biosynthesis inhibitor increased na nodule numbers. However, these nodules were still aberrant in structure. • Constitutive GA signalling mutants also form significantly fewer nodules than wild-type plants. This suggests that there is an optimum degree of GA signalling required for nodule formation and that the GA signal, and not the concentration of bioactive GA per se, is important for nodulation.
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Delta-sarcoglycan gene therapy halts progression of cardiac dysfunction, improves respiratory failure, and prolongs life in myopathic hamsters.
Circ Heart Fail
PUBLISHED: 10-29-2010
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The BIO14.6 hamster provides a useful model of hereditary cardiomyopathies and muscular dystrophy. Previous ?-sarcoglycan (?SG) gene therapy (GT) studies were limited to neonatal and young adult animals and prevented the development of cardiac and skeletal muscle dysfunction. GT of a pseudophosphorylated mutant of phospholamban (S16EPLN) moderately alleviated the progression of cardiomyopathy.
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Reassessing the role of N-hydroxytryptamine in auxin biosynthesis.
Plant Physiol.
PUBLISHED: 10-25-2010
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The tryptamine pathway is one of five proposed pathways for the biosynthesis of indole-3-acetic acid (IAA), the primary auxin in plants. The enzymes AtYUC1 (Arabidopsis thaliana), FZY (Solanum lycopersicum), and ZmYUC (Zea mays) are reported to catalyze the conversion of tryptamine to N-hydroxytryptamine, putatively a rate-limiting step of the tryptamine pathway for IAA biosynthesis. This conclusion was based on in vitro assays followed by mass spectrometry or HPLC analyses. However, there are major inconsistencies between the mass spectra reported for the reaction products. Here, we present mass spectral data for authentic N-hydroxytryptamine, 5-hydroxytryptamine (serotonin), and tryptamine to demonstrate that at least some of the published mass spectral data for the YUC in vitro product are not consistent with N-hydroxytryptamine. We also show that tryptamine is not metabolized to IAA in pea (Pisum sativum) seeds, even though a PsYUC-like gene is strongly expressed in these organs. Combining these findings, we propose that at present there is insufficient evidence to consider N-hydroxytryptamine an intermediate for IAA biosynthesis.
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mRNA for the EAAC1 subtype of glutamate transporter is present in neuronal dendrites in vitro and dramatically increases in vivo after a seizure.
Neurochem. Int.
PUBLISHED: 09-22-2010
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The neuronal Na(+)-dependent glutamate transporter, excitatory amino acid carrier 1 (EAAC1, also called EAAT3), has been implicated in the control of synaptic spillover of glutamate, synaptic plasticity, and the import of cysteine for neuronal synthesis of glutathione. EAAC1 protein is observed in both perisynaptic regions of the synapse and in neuronal cell bodies. Although amino acid residues in the carboxyl terminal tail have been implicated in the dendritic targeting of EAAC1 protein, it is not known if mRNA for EAAC1 may also be targeted to dendrites. Sorting of mRNA to specific cellular domains provides a mechanism by which signals can rapidly increase translation in a local environment; this form of regulated translation has been linked to diverse biological phenomena ranging from establishment of polarity during embryogenesis to synapse development and synaptic plasticity. In the present study, EAAC1 mRNA sequences were amplified from dendritic samples that were mechanically harvested from low-density hippocampal neuronal cultures. In parallel analyses, mRNA for histone deacetylase 2 (HDAC-2) and glial fibrillary acidic protein (GFAP) was not detected, suggesting that these samples are not contaminated with cell body or glial mRNAs. EAAC1 mRNA also co-localized with Map2a (a marker of dendrites) but not Tau1 (a marker of axons) in hippocampal neuronal cultures by in situ hybridization. In control rats, EAAC1 mRNA was observed in soma and proximal dendrites of hippocampal pyramidal neurons. Following pilocarpine- or kainate-induced seizures, EAAC1 mRNA was present in CA1 pyramidal cell dendrites up to 200?m from the soma. These studies provide the first evidence that EAAC1 mRNA localizes to dendrites and suggest that dendritic targeting of EAAC1 mRNA is increased by seizure activity and may be regulated by neuronal activity/depolarization.
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Augmentation of abscisic acid (ABA) levels by drought does not induce short-term stomatal sensitivity to CO2 in two divergent conifer species.
J. Exp. Bot.
PUBLISHED: 08-25-2010
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The stomata of conifers display very little short-term response to changes in atmospheric CO(2) concentration (C(a)), whereas the stomatal responses of angiosperms to C(a) increase in response to water stress. This behaviour of angiosperm stomata appears to be dependent on foliar levels of abscisic acid (ABA(f)). Here two alternative explanations for the stomatal insensitivity of conifers to C(a) are tested: that conifers have either low ABA(f) or a higher or absent threshold for ABA-induced sensitivity. The responsiveness of stomatal conductance (g(s)) to a sequence of transitions in C(a) (386, 100, and 600??mol mol(-1)) was recorded over a range of ABA(f) in an angiosperm and two divergent conifer species. The different ABA levels were induced by a mild drought cycle. Although the angiosperm and conifer species showed similar proportional increases in ABA(f) following drought, conifer stomata remained insensitive to changes in C(a) whereas angiosperm stomata showed enhanced sensitivity with increasing ABA(f). The conifers, however, had much higher ABA(f) prior to drought than the angiosperm species, suggesting that non-sensitivity to C(a) in these conifers was due to an absent or inactive response/signalling pathway rather than insufficient ABA(f).
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Underestimation of perceived number at the time of saccades.
Vision Res.
PUBLISHED: 08-24-2010
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Saccadic eye movements produce transient distortions in both space and time. Mounting evidence suggests that space and time perception are linked, and associated with the perception of another important perceptual attribute, numerosity. Here we investigate the effect of saccades on the perceived numerosity of briefly presented arrays of visual elements. We report a systematic underestimation of numerosity for stimuli flashed just before or during saccades, of about 35% of the reference numerosity. The bias is observed only for relatively large arrays of visual elements, in line with the notion that a distinct perceptual mechanism is involved with enumeration of small numerosities in the subitizing range. This study provides further evidence for the notion that space, time and number share common neural representations, all affected by saccades.
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Changes in foetal liver T2* measurements by MRI in response to maternal oxygen breathing: application to diagnosing foetal growth restriction.
Physiol Meas
PUBLISHED: 07-23-2010
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The motivation of the project was to investigate the use of oxygen-challenge magnetic resonance imaging (OC-MRI) as a method of diagnosing foetal growth restriction. Foetal growth restriction is associated with restricted foetal oxygen supply and is also associated with increased risks of perinatal mortality and morbidity, and a number of serious and chronic health problems. Measurements of T2* relaxation time, an MRI parameter which increases with blood oxygenation, were made in the right lobe of the foetal liver in 80 singleton pregnancies, before and after the mother breathed oxygen. The groups consisted of 41 foetuses with normal growth and 39 with apparent growth restriction. The mean +/- SD gestational age at scanning was 35 +/- 3 weeks. Changes in foetal liver T2* on maternal oxygen breathing showed no significant difference between the groups therefore the OC-MRI protocol used in this study has no value in the diagnosis of foetal growth restriction. A secondary finding was that a significant positive correlation of T2* change with gestational age was observed. Future studies on the use of oxygen-challenge MRI to investigate foetal growth restriction may therefore need to control for gestational age at the time of MR scanning in order to observe any underlying foetal growth-related effects.
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Saccades compress space, time and number.
Trends Cogn. Sci. (Regul. Ed.)
PUBLISHED: 07-18-2010
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It has been suggested that space, time and number are represented on a common subjective scale. Saccadic eye movements provide a fascinating test. Saccades compress the perceived magnitude of spatial separations and temporal intervals to approximately half of their true value. The question arises as to whether saccades also compress number. They do, and compression follows a very similar time course for all three attributes: it is maximal at saccadic onset and decreases to veridicality within a window of approximately 50ms. These results reinforce the suggestion of a common perceptual metric, which is probably mediated by the intraparietal cortex; they further suggest that before each saccade the common metric for all three is reset, possibly to pave the way for a fresh analysis of the post-saccadic situation.
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Purification of a recombinant heavy chain fragment C vaccine candidate against botulinum serotype C neurotoxin [rBoNTC(H(c))] expressed in Pichia pastoris.
Protein Expr. Purif.
PUBLISHED: 07-15-2010
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A purification process for the manufacture of a recombinant C-terminus heavy chain fragment from botulinum neurotoxin serotype C [rBoNTC(H(c))], a potential vaccine candidate, has been defined and successfully scaled-up. The rBoNTC(H(c)) was produced intracellularly in Pichia pastoris X-33 using a three step fermentation process, i.e., glycerol batch phase, a glycerol fed-batch phase to achieve high cell densities, followed by a methanol induction phase. The rBoNTC(H(c)) was captured from the soluble protein fraction of cell lysate using hydrophobic charge induction chromatography (HCIC; MEP HyperCel™), and then further purified using a CM 650M ion exchange chromatography step followed by a polishing step using HCIC once again. Method development at the bench scale was achieved using 5-100mL columns and the process was performed at the pilot scale using 0.6-1.6L columns in preparation for technology transfer to cGMP manufacturing. The process yielded approximately 2.5 g of rBoNTC(H(c))/kg wet cell weight (WCW) at the bench scale and 1.6 g rBoNTC(H(c))/kg WCW at the pilot scale. The purified rBoNTC(H(c)) was stable for at least 3 months at 5 and -80°C as determined by reverse phase-HPLC and SDS-PAGE and was stable for 24 months at -80 °C based on mouse potency bioassay. N-Terminal amino acid sequencing confirmed that the N-terminus of the purified rBoNTC(H(c)) was intact.
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A generalized Fisher equation and its utility in chemical kinetics.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 07-06-2010
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A generalized Fisher equation (GFE) relates the time derivative of the average of the intrinsic rate of growth to its variance. The GFE is an exact mathematical result that has been widely used in population dynamics and genetics, where it originated. Here we demonstrate that the GFE can also be useful in other fields, specifically in chemistry, with models of two chemical reaction systems for which the mechanisms and rate coefficients correspond reasonably well to experiments. A bad fit of the GFE can be a sign of high levels of measurement noise; for low or moderate levels of noise, fulfillment of the GFE is not degraded. Hence, the GFE presents a noise threshold that may be used to test the validity of experimental measurements without requiring any additional information. In a different approach information about the system (model) is included in the calculations. In that case, the discrepancy with the GFE can be used as an optimization criterion for the determination of rate coefficients in a given reaction mechanism.
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Regulation of the gibberellin pathway by auxin and DELLA proteins.
Planta
PUBLISHED: 05-19-2010
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The synthesis and deactivation of bioactive gibberellins (GA) are regulated by auxin and by GA signalling. The effect of GA on its own pathway is mediated by DELLA proteins. Like auxin, the DELLAs promote GA synthesis and inhibit its deactivation. Here, we investigate the relationships between auxin and DELLA regulation of the GA pathway in stems, using a pea double mutant that is deficient in DELLA proteins. In general terms our results demonstrate that auxin and DELLAs independently regulate the GA pathway, contrary to some previous suggestions. The extent to which DELLA regulation was able to counteract the effects of auxin regulation varied from gene to gene. For Mendels LE gene (PsGA3ox1) no counteraction was observed. However, for another synthesis gene, a GA 20-oxidase, the effect of auxin was weak and in WT plants appeared to be completely over-ridden by DELLA regulation. For a key GA deactivation (2-oxidase) gene, PsGA2ox1, the up-regulation induced by auxin deficiency was reduced to some extent by DELLA regulation. A second pea 2-oxidase gene, PsGA2ox2, was up-regulated by auxin, in a DELLA-independent manner. In Arabidopsis also, one 2-oxidase gene was down-regulated by auxin while another was up-regulated. Monitoring the metabolism pattern of GA(20) showed that in Arabidopsis, as in pea, auxin can promote the accumulation of bioactive GA.
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European survey of the level of satisfaction of patients and physicians in the management of epilepsy in general practice.
Epilepsy Behav
PUBLISHED: 04-30-2010
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Many people with epilepsy report treatment-emergent adverse effects (AEs) while on drug therapy despite optimized treatment. We explored the level of treatment satisfaction with current management among people with epilepsy and treating physicians from seven different European countries. There was discordance between patients and physicians: patients would like greater involvement in discussions regarding treatment options and, although generally satisfied with their current medication, saw the need for a more effective balance between seizure control and AEs. Conversely, physicians were less satisfied with current treatments, but were less concerned with AEs. People with epilepsy also wanted to be better educated about epilepsy and its management. Key challenges for the future include improvement in the self-management of epilepsy by patients and more proactive patient-physician interactions. An additional aim is to improve the publics perception of epilepsy so as to remove any associated stigma.
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Deposition and spatial distribution of insecticides following fogger, perimeter sprays, spot sprays, and crack-and-crevice applications for treatment and control of indoor pests.
Regul. Toxicol. Pharmacol.
PUBLISHED: 04-19-2010
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The indoor surface deposition and distribution of insecticides applied as foggers, baseboard or perimeter sprays, spot sprays and crack-and-crevice sprays represent distinct pathways of potential unintentional and unavoidable residential pesticide exposure of children and adults. Fogger, perimeter spray, crack-and-crevice, and spot sprays using registered commercial products were studied using three 5-part deposition plates positioned in unoccupied residences in Riverside, CA. Pesticide active ingredients included permethrin, chlorpyrifos, cyfluthrin, cypermethrin, and deltamethrin. Horizontal distribution factors of 100% (total release fogger in a small room), 50% (perimeter spray), 15% (crack-and-crevice), and 2% (spot spray) were assigned based upon application of selected commercial products by a licensed pest control operator and investigators who participated in these studies. This research reduces uncertainties associated with assessing human exposure following different application methods.
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Pharmacy cost sharing, antiplatelet therapy utilization, and health outcomes for patients with acute coronary syndrome.
Am J Manag Care
PUBLISHED: 04-17-2010
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To examine how cost sharing for prescription drugs affects compliance with antiplatelet therapy and subsequent health outcomes among patients with acute coronary syndrome (ACS).
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Hydrogen/deuterium exchange on aromatic rings during atmospheric pressure chemical ionization mass spectrometry.
Rapid Commun. Mass Spectrom.
PUBLISHED: 03-10-2010
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It has been demonstrated that substituted indoles fully labelled with deuterium on the aromatic ring can undergo substantial exchange back to partial and even fully protonated forms during atmospheric pressure chemical ionisation (APCI) liquid chromatography/mass spectrometry (LC/MS). The degree of this exchange was strongly dependent on the absolute quantity of analyte, the APCI desolvation temperature, the nature of the mobile phase, the mobile phase flow rate and the instrument used. Hydrogen/deuterium (H/D) exchange on several other aromatic ring systems during APCI LC/MS was either undetectable (nitrobenzene, aniline) or extremely small (acetanilide) compared to the effect observed for substituted indoles. This observation has major implications for quantitative assays using deuterium-labelled internal standards and for the detection of deuterium-labelled products from isotopically labelled feeding experiments where there is a risk of back exchange to the protonated form during the analysis.
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Stent graft versus balloon angioplasty for failing dialysis-access grafts.
N. Engl. J. Med.
PUBLISHED: 02-12-2010
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The leading cause of failure of a prosthetic arteriovenous hemodialysis-access graft is venous anastomotic stenosis. Balloon angioplasty, the first-line therapy, has a tendency to lead to subsequent recoil and restenosis; however, no other therapies have yet proved to be more effective. This study was designed to compare conventional balloon angioplasty with an expanded polytetrafluoroethylene endovascular stent graft for revision of venous anastomotic stenosis in failing hemodialysis grafts.
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Vision senses number directly.
J Vis
PUBLISHED: 01-13-2010
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We have recently suggested that numerosity is a primary sensory attribute, and shown that it is strongly susceptible to adaptation. Here we use the Method of Single Stimuli to show that observers can extract a running average of numerosity of a succession of stimuli to use as a standard of comparison for subsequent stimuli. On separate sessions observers judged whether the perceived numerosity or density of a particular trial was greater or less than the average of previous stimuli. Thresholds were as precise for this task as for explicit comparisons of test with standard stimuli. Importantly, we found no evidence that numerosity judgments are mediated by density. Under all conditions, judgements of numerosity were as precise as those of density. Thresholds in intermingled conditions, where numerosity varied unpredictably with density, were as precise as the blocked thresholds. Judgments in constant-density conditions were more precise thresholds than those in variable-density conditions, and numerosity judgements in conditions of constant-numerosity showed no tendency to follow density. We further report the novel finding that perceived numerosity increases with decreasing luminance, whereas texture density does not, further evidence for independent processing of the two attributes. All these measurements suggest that numerosity judgments can be, and are, made independently of judgments of the density of texture.
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Gene expression profiling identifies two regulatory genes controlling dormancy and ABA sensitivity in Arabidopsis seeds.
Plant J.
PUBLISHED: 11-26-2009
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Seed dormancy is a very important trait that maximizes the survival of seed in nature, the control of which can have important repercussions on the yield of many crop species. We have used gene expression profiling to identify genes that are involved in dormancy regulation in Arabidopsis thaliana. RNA was isolated from imbibed dormant (D) and after-ripened (AR) ecotype C24 seeds, and then screened by quantitative RT-PCR (qRT-PCR) for differentially expressed transcription factors (TFs) and other regulatory genes. Out of 2207 genes screened, we have identified 39 that were differentially expressed during the first few hours of imbibition. After analyzing T-DNA insertion mutants for 22 of these genes, two displayed altered dormancy compared with the wild type. These mutants are affected in genes that encode a RING finger and an HDZip protein. The first, named DESPIERTO, is involved in ABA sensitivity during seed development, regulates the expression of ABI3, and produces a complete loss of dormancy when mutated. The second, the HDZip (ATHB20), is expressed during seed germination in the micropylar endosperm and in the root cap, and increases ABA sensitivity and seed dormancy when mutated.
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Hearing symptoms and audiometry in professional divers and offshore workers.
Occup Med (Lond)
PUBLISHED: 11-13-2009
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The aims are to compare hearing loss between professional divers and offshore workers and to study whether hearing loss symptoms reflected physical disorder. A secondary objective was to study total threshold shift assessment as a method of detecting noise-induced hearing loss (NIHL).
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Auxin biosynthesis in pea: characterization of the tryptamine pathway.
Plant Physiol.
PUBLISHED: 08-26-2009
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One pathway leading to the bioactive auxin, indole-3-acetic acid (IAA), is known as the tryptamine pathway, which is suggested to proceed in the sequence: tryptophan (Trp), tryptamine, N-hydroxytryptamine, indole-3-acetaldoxime, indole-3-acetaldehyde (IAAld), IAA. Recently, this pathway has been characterized by the YUCCA genes in Arabidopsis (Arabidopsis thaliana) and their homologs in other species. YUCCA is thought to be responsible for the conversion of tryptamine to N-hydroxytryptamine. Here we complement the genetic findings with a compound-based approach in pea (Pisum sativum), detecting potential precursors by gas chromatography/tandem-mass spectrometry. In addition, we have synthesized deuterated forms of many of the intermediates involved, and have used them to quantify the endogenous compounds, and to investigate their metabolic fates. Trp, tryptamine, IAAld, indole-3-ethanol, and IAA were detected as endogenous constituents, whereas indole-3-acetaldoxime and one of its products, indole-3-acetonitrile, were not detected. Metabolism experiments indicated that the tryptamine pathway to IAA in pea roots proceeds in the sequence: Trp, tryptamine, IAAld, IAA, with indole-3-ethanol as a side-branch product of IAAld. N-hydroxytryptamine was not detected, but we cannot exclude that it is an intermediate between tryptamine and IAAld, nor can we rule out the possibility of a Trp-independent pathway operating in pea roots.
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Assessing exposure to allied ground troops in the Vietnam War: a comparison of AgDRIFT and Exposure Opportunity Index models.
J Expo Sci Environ Epidemiol
PUBLISHED: 06-16-2009
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The AgDRIFT aerial dispersion model is well validated and closely related to the AGDISP model developed by the USDA Forest Service to determine on- and off-target deposition and penetration of aerially applied pesticide through foliage of trees. The Exposure Opportunity Index (EOI) model was developed to estimate relative exposure of ground troops in Vietnam to aerially applied herbicides. We compared the output of the two models to determine whether their predictions were in substantial agreement, but found a total lack of concordance. While the AgDRIFT model estimated that ground-level deposition through foliage was reduced more than 20 orders of magnitude at less than 1 km from the flight line, the EOI model predicted deposition declines less than one order of magnitude 4 km from the flight line. Interestingly the EOI model predicts a four-fold variability in EOI on the flight line, where exposure should be essentially invariant because the spray apparatus is designed to apply herbicide at a constant rate. We believe that the EOI model cannot be used to provide individual exposure estimates for the purpose of conducting epidemiologic studies. Moreover, evaluation of the position data for both herbicide spray swaths and troop locations, together with the actual patterns of spray deposition predicted by the AgDRIFT model, suggests that precise individual-level exposure assessments for ground troops in Vietnam are impossible. However, we suggest that well-validated tools like AgDRIFT can be used to estimate exposure to groups of individuals.
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Saturation treatment in shore-based chambers for divers with deteriorating cerebro-spinal decompression sickness.
Diving Hyperb Med
PUBLISHED: 04-30-2009
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Nearly 4% of all primary recompression treatments in Scotland employ saturation tables (helium/oxygen-oxygen/air or oxygen/air alone). These cases usually involve divers presenting at the surface who then develop deteriorating spinal cord injury with varying degrees of cerebral involvement. Treatment is delivered either through immediate saturation therapy or through conversion of failing or failed primary treatment. The basic principles and delivery protocols of saturation treatment are outlined. A case study from both types of treatment is presented to illustrate the forms of decompression sickness that may require saturation treatment and how the treatments are initiated and evolve.
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A 50-year research journey. From laboratory to clinic.
Circ. J.
PUBLISHED: 04-22-2009
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Prior important research is not always cited, exemplified by Oswald Averys pioneering discovery that DNA is the genetic transforming factor; it was not cited by Watson and Crick 10 years later. My first laboratory research (National Institutes of Health 1950s) resulted in the clinical development of transseptal left heart catheterization. Laboratory studies on cardiac muscle mechanics in normal and failing hearts led to the concept of afterload mismatch with limited preload reserve. At the University of California, San Diego in La Jolla (1968) laboratory experiments on coronary artery reperfusion after sustained coronary occlusion showed salvage of myocardial tissue, a potential treatment for acute myocardial infarction proven in clinical trials of thrombolysis 14 years later. Among 60 trainees who worked with me in La Jolla, one-third were Japanese and some of their important laboratory experiments are briefly recounted, beginning with Sasayama, Tomoike and Shirato in the 1970 s. Recently, we developed a method for cardiac gene transfer, and subsequently we showed that gene therapy for the defect in cardiomyopathic hamsters halted the progression of advanced disease. Cardiovascular research and medicine are producing continuing advances in technologies for gene transfer and embryonic stem cell transplantation, targeting of small molecules, and tissue and organ engineering.
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Analyses of treatment for divers with actual or suspected decompression illness.
Diving Hyperb Med
PUBLISHED: 04-16-2009
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We examined national and single-centre datasets in Scotland to determine any trends in the treatment of diving-related disease and to assess how the choice of first treatment may be linked to the divers condition on referral and on discharge.
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Relationship of infantile periocular hemangioma depth to growth and regression pattern.
J AAPOS
PUBLISHED: 04-13-2009
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Most infantile periocular hemangiomas undergo rapid growth in the first year of life, followed by gradual resolution over years. Treatment is indicated if vision is compromised and is usually continued through the growth phase. The objective of this study was to determine which clinical characteristics might aid in the prediction of growth and/or regression patterns of periocular hemangiomas.
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Kinetic laws, phase-phase expansions, renormalization group, and INR calibration.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 04-06-2009
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We introduce systematic approaches to chemical kinetics based on the use of phase-phase (log-log) representations of the rate equations. For slow processes, we obtain a corrected form of the mass-action law, where the concentrations are replaced by kinetic activities. For fast reactions, delay expressions are derived. The phase-phase expansion is, in general, applicable to kinetic and transport processes. A mechanism is introduced for the occurrence of a generalized mass-action law as a result of self-similar recycling. We show that our self-similar recycling model applied to prothrombin assays reproduces the empirical equations for the International Normalized Ratio calibration (INR), as well as the Watala, Golanski, and Kardas relation (WGK) for the dependence of the INR on the concentrations of coagulation factors. Conversely, the experimental calibration equation for the INR, combined with the experimental WGK relation, without the use of theoretical models, leads to a generalized mass-action type kinetic law.
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Light regulation of gibberellin biosynthesis in pea is mediated through the COP1/HY5 pathway.
Plant Cell
PUBLISHED: 03-27-2009
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Light regulation of gibberellin (GA) biosynthesis occurs in several species, but the signaling pathway through which this occurs has not been clearly established. We have isolated a new pea (Pisum sativum) mutant, long1, with a light-dependent elongated phenotype that is particularly pronounced in the epicotyl and first internode. The long1 mutation impairs signaling from phytochrome and cryptochrome photoreceptors and interacts genetically with a mutation in LIP1, the pea ortholog of Arabidopsis thaliana COP1. Mutant long1 seedlings show a dramatic impairment in the light regulation of active GA levels and the expression of several GA biosynthetic genes, most notably the GA catabolism gene GA2ox2. The long1 mutant carries a nonsense mutation in a gene orthologous to the ASTRAY gene from Lotus japonicus, a divergent ortholog of the Arabidopsis bZIP transcription factor gene HY5. Our results show that LONG1 has a central role in mediating the effects of light on GA biosynthesis in pea and demonstrate the importance of this regulation for appropriate photomorphogenic development. By contrast, LONG1 has no effect on GA responsiveness, implying that interactions between LONG1 and GA signaling are not a significant component of the molecular framework for light-GA interactions in pea.
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Angiographic and clinical outcomes of drug-eluting versus bare metal stent deployment in the Occluded Artery Trial.
Catheter Cardiovasc Interv
PUBLISHED: 03-25-2009
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The majority of patients randomized to percutaneous coronary intervention (PCI) in the Occluded Artery Trial (OAT) and its angiographic substudy, the Total Occlusion Study of Canada 2 (TOSCA-2) were treated with bare metal stents (BMS). We aimed to determine if stenting of the target occlusion in OAT with drug-eluting stents (DES) was associated with more favorable angiographic results and clinical outcome when compared with treatment with BMS.
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Initial experience and outcome of a new hemodialysis access device for catheter-dependent patients.
J. Vasc. Surg.
PUBLISHED: 03-16-2009
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The effects of a new long-term subcutaneous vascular access device were studied in access-challenged patients who were poor candidates for fistulas or grafts due to venous obstruction. Bacteremia rates, patency, and function of the Hemodialysis Reliable Outflow (HeRO) Vascular Access Device (Hemosphere Inc, Minneapolis, Minn) were evaluated.
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How increased contraceptive use has reduced maternal mortality.
Matern Child Health J
PUBLISHED: 03-14-2009
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It is widely recognized that family planning contributes to reducing maternal mortality by reducing the number of births and, thus, the number of times a woman is exposed to the risk of mortality. Here we show evidence that it also lowers the risk per birth, the maternal mortality ratio (MMR), by preventing high-risk, high-parity births. This study seeks to quantify these contributions to lower maternal mortality as the use of family planning rose over the period from 1990 to 2005. We use estimates from United Nations organizations of MMRs and the total fertility rate (TFR) to estimate the number of births averted-and, consequently, the number of maternal deaths directly averted-as the TFR in the developing world dropped. We use data from 146 Demographic and Health Surveys on contraceptive use and the distribution of births by risk factor, as well as special country data sets on the MMR by parity and age, to explore the impacts of contraceptive use on high-risk births and, thus, on the MMR. Over 1 million maternal deaths were averted between 1990 and 2005 because the fertility rate in developing countries declined. Furthermore, by reducing demographically high-risk births in particular, especially high-parity births, family planning reduced the MMR and thus averted additional maternal deaths indirectly. This indirect effect can reduce a countys MMR by an estimated 450 points during the transition from low to high levels of contraceptive use. Increases in the use of modern contraceptives have made and can continue to make an important contribution to reducing maternal mortality in the developing world.
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Emergency recompression: clinical audit of service delivery at a national level.
Diving Hyperb Med
PUBLISHED: 03-01-2009
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Clinical audit is an essential element to the maintenance or improvement of delivery of any medical service. During the development phase of a National Recompression Registration Service for Scotland, clinical audit was initiated to provide a standardised tool to monitor the quality of outcome with respect to the severity of presentation. A functional audit process was an essential consideration for planned future measurement of treatment efficacy at local (single hyperbaric unit) and national (multiple hyperbaric units) scales. The audit process was designed to be undemanding, robust and informative, irrespective of the experience of treatment centre and of the clinician in charge of treatment. The clinical records from 104 cases of divers with decompression illness were used to derive and evaluate measures of severity and clinical outcome that could be used for audit and quality assurance. The various measures of disease severity were examined against clinical outcome and days spent in care after admission to a hyperbaric unit. An initial version of the clinical audit format that was developed from this process is presented.
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Impact of stress testing before percutaneous coronary intervention or medical management on outcomes of patients with persistent total occlusion after myocardial infarction: analysis from the occluded artery trial.
Am. Heart J.
PUBLISHED: 02-23-2009
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In the Occluded Artery Trial (OAT), 2,201 stable patients with an occluded infarct-related artery (IRA) were randomized to percutaneous coronary intervention (PCI) or optimal medical treatment alone (MED). There was no difference in the primary end point of death, reinfarction, or congestive heart failure (CHF). We examined the prognostic impact of prerandomization stress testing.
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Quality of life after late invasive therapy for occluded arteries.
N. Engl. J. Med.
PUBLISHED: 02-21-2009
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The open-artery hypothesis postulates that late opening of an infarct-related artery after myocardial infarction will improve clinical outcomes. We evaluated the quality-of-life and economic outcomes associated with the use of this strategy.
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Contemporary management of pregnancy-related coronary artery dissection: A single-centre experience and literature review.
Exp Clin Cardiol
PUBLISHED: 02-17-2009
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Spontaneous coronary artery dissection (SCAD) is an infrequent event that is most commonly associated with pregnant women or those in the postpartum period. Because of its rarity, the literature describing this condition is confined to sporadic case reports, with few reporting long-term follow-up, and no clear consensus exists on the optimal treatment strategy for these patients. The present article reports a single-centre experience with SCAD, highlighting the issues surrounding its management with a brief description of five cases of pregnancy-associated coronary dissection. The treatment used in these cases ranged from a conservative medical approach to surgical and percutaneous intervention, with one patient proceeding to transplantation. Four of the cases have long-term angiographic follow-up.In addition, a comprehensive review of all previously published cases is presented, and temporal trends in the management strategy are highlighted. Possible pathophysiological mechanisms pertaining to this condition, and the complex diagnostic and therapeutic issues involved, which may affect both patient and fetus, are discussed. Finally, an optimal approach to patients with SCAD, informed by our experience and literature review, is described.
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What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

Video X seems to be unrelated to Abstract Y...

In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.