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Search Results: 1 - 10 of 189894 matches for " G. Mackin "
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Tracking Differential Gene Expression in MRL/MpJ Versus C57BL/6 Anergic B Cells: Molecular Markers of Autoimmunity
Amy G. Clark,Katherine M. Mackin,Mary H. Foster
Biomarker Insights , 2008,
Abstract: Background: Anergy is a key mechanism controlling expression of autoreactive B cells and a major site for failed regulation in autoimmune diseases. Yet the molecular basis for this differentiated cell state remains poorly understood. The current lack of well-characterized surface or molecular markers hinders the isolation of anergic cells for further study. Global gene profiling recently identified transcripts whose expression differentiates anergic from na ve B cells in model mouse systems. The objective of the current study was to evaluate the molecular and cellular processes that differentiate anergic cells that develop in the healthy C57BL/6 (B6) milieu from those that develop in the autoimmune-prone MRL/MpJ (MRL) background. This approach takes advantage of B6 and MRL mice bearing an anti-laminin Ig transgene with a well characterized anergic B cell phenotype.Results: Global gene expression was evaluated in purified transgenic B cells using Operon version 3.0 oligonucleotide microarray assaying 31,000 oligoprobes. Genes with a 2-fold expression difference in B6 as compared to MRL anergic B cells were identified. Expression of selected genes was confirmed using quantitative RT-PCR. This approach identified 43 probes corresponding to 37 characterized genes, including Ptpn22, CD74, Birc1f/Naip, and Ctla4, as differentially expressed in anergic B cells in the two strains. Gene Ontology classification identified differentiation, cell cycle, proliferation, development, apoptosis, and cell death as prominently represented ontology groups. Ingenuity Pathway Analysis identified two major networks incorporating 27 qualifying genes. Network 1 centers on beta-estradiol and TP53, and Network 2 encompasses RB1, p38 MAPK, and NFkB cell growth, proliferation, and cell cycle signaling pathways.Conclusion: Using microarray analysis we identified 37 characterized genes and two functional pathways engaged in maintenance of B cell anergy for which expression is distorted by underlying autoimmune genetic susceptibility. This approach identifies a new biological role for multiple genes and potential new therapeutic targets in autoimmunity.
Influence of basin connectivity on sediment source, transport, and storage within the Mkabela Basin, South Africa
J. R. Miller,G. Mackin,P. Lechler,M. Lord
Hydrology and Earth System Sciences Discussions , 2012, DOI: 10.5194/hessd-9-10151-2012
Abstract: The management of sediment and other non-point source (NPS) pollution has proven difficult, and requires a sound understanding of particle movement through the drainage system. The primary objective of this investigation was to obtain an understanding of NPS sediment source(s), transport, and storage within the Mkabela basin, a representative agricultural catchment within the KwaZulu-Natal Midlands of southeastern South Africa, by combining geomorphic, hydrologic and geochemical fingerprinting analyses. The Mkabela Basin can be subdivided into three distinct subcatchments that differ in their ability to transport and store sediment along the axial valley. Headwater (upper catchment) areas are characterized by extensive wetlands that act as significant sediment sinks. Mid-catchment areas, characterized by higher relief and valley gradients, exhibit few wetlands, but rather are dominated by a combination of alluvial and bedrock channels that are conducive to sediment transport. The lower catchment exhibits a low-gradient alluvial channel that is boarded by extensive riparian wetlands that accumulate large quantities of sediment (and NPS pollutants). Fingerprinting studies suggest that silt- and clay-rich layers found within wetland and reservoir deposits are derived from the erosion of fine-grained, valley bottom soils frequently utilized as vegetable fields. Coarser-grained deposits within both wetlands and reservoirs result from the erosion of sandier hillslope soils extensively utilized for sugar cane, during relatively high magnitude runoff events that are capable of transporting sand-sized sediment off the slopes. Thus, the source of sediment to the axial valley varies as a function of sediment size and runoff magnitude. Sediment export from the basin was limited until the early 1990s, in part because the upper catchment wetlands were hydrologically disconnected from lower parts of the watershed during low- to moderate flood events. The construction of a drainage ditch through a previously unchanneled wetland altered the hydrologic connectivity of the catchment, allowing sediment to be transported from the headwaters to the lower basin where much of it was deposited within the riparian wetlands. The axial drainage system is now geomorphically and hydrologically connected during most events throughout the study basin. The study indicates that increased valley connectivity partly negated the positive benefits of controlling sediment/nutrient exports from the catchment by means of upland based, best management practices.
Influence of basin connectivity on sediment source, transport, and storage within the Mkabela Basin, South Africa
J. R. Miller, G. Mackin, P. Lechler, M. Lord,S. Lorentz
Hydrology and Earth System Sciences (HESS) & Discussions (HESSD) , 2013,
Abstract: The management of sediment and other non-point source (NPS) pollution has proven difficult, and requires a sound understanding of particle movement through the drainage system. The primary objective of this investigation was to obtain an understanding of NPS sediment source(s), transport, and storage within the Mkabela Basin, a representative agricultural catchment within the KwaZulu–Natal Midlands of eastern South Africa, by combining geomorphic, hydrologic and geochemical fingerprinting analyses. The Mkabela Basin can be subdivided into three distinct subcatchments that differ in their ability to transport and store sediment along the axial valley. Headwater (upper catchment) areas are characterized by extensive wetlands that act as significant sediment sinks. Mid-catchment areas, characterized by higher relief and valley gradients, exhibit few wetlands, but rather are dominated by a combination of alluvial and bedrock channels that are conducive to sediment transport. The lower catchment exhibits a low-gradient alluvial channel that is boarded by extensive riparian wetlands that accumulate large quantities of sediment (and NPS pollutants). Fingerprinting studies suggest that silt- and clay-rich layers found within wetland and reservoir deposits of the upper and upper-mid subcatchments are derived from the erosion of fine-grained, valley bottom soils frequently utilized as vegetable fields. Coarser-grained deposits within these wetlands and reservoirs result from the erosion of sandier hillslope soils extensively utilized for sugar cane, during relatively high magnitude runoff events that are capable of transporting sand-sized sediment off the slopes. Thus, the source of sediment to the axial valley varies as a function of sediment size and runoff magnitude. Sediment export from upper to lower catchment areas was limited until the early 1990s, in part because the upper catchment wetlands were hydrologically disconnected from lower parts of the watershed during low to moderate flood events. The construction of a drainage ditch through a previously unchanneled wetland altered the hydrologic connectivity of the catchment, allowing sediment to be transported from the headwaters to the lower basin where much of it was deposited within riparian wetlands. The axial drainage system is now geomorphically and hydrologically connected during events capable of overflowing dams located throughout the study basin. The study indicates that increased valley connectivity partly negated the positive benefits of controlling sediment/nutrient exports from the catchment by means of upland based, best management practices.
Allocating Indivisible Items in Categorized Domains
Erika Mackin,Lirong Xia
Computer Science , 2015,
Abstract: We formulate a general class of allocation problems called categorized domain allocation problems (CDAPs), where indivisible items from multiple categories are allocated to agents without monetary transfer and each agent gets at least one item per category. We focus on basic CDAPs, where the number of items in each category is equal to the number of agents. We characterize serial dictatorships for basic CDAPs by a minimal set of three axiomatic properties: strategy-proofness, non-bossiness, and category-wise neutrality. Then, we propose a natural extension of serial dictatorships called categorial sequential allocation mechanisms (CSAMs), which allocate the items in multiple rounds: in each round, the active agent chooses an item from a designated category. We fully characterize the worst-case rank efficiency of CSAMs for optimistic and pessimistic agents, and provide a bound for strategic agents. We also conduct experiments to compare expected rank efficiency of various CSAMs w.r.t. random generated data.
Market Simulation Displaying Multifractality
Kazuko Yamasaki,Kenneth J. Mackin
Quantitative Finance , 2003,
Abstract: We proposed a market simulation model (micro model) which displays multifractality and reproduces many important stylized facts of speculative markets. From this model we analytically extracted the MMAR model (Multifractal Model of Asset Returns) for the macroscopic limit.
Island Activities Detected by VIIRS and Validation with AIS  [PDF]
Ichio Asanuma, Daisuke Hasegawa, Takashi Yamaguchi, Jong Geol Park, Kenneth James Mackin
Advances in Remote Sensing (ARS) , 2018, DOI: 10.4236/ars.2018.73012
Abstract: A possibility to monitor the reclamation activities by remote sensing was discussed. The lights observed in the night time by Day Night Band (DNB) of Visible Infrared Imaging Radiometer Suite (VIIRS), ocean color observed in the day time by visible bands of VIIRS were the tools to monitor the surface activities, and the Automated Information System (AIS) was used to verify the types and number of vessels associated with the reclamation activities. The lights as the radiance from the surface were monitored by the object based analysis, where the object was defined as a radius of 5 km from the center of the Mischief Reef in the South China Sea (SCS). The time history of surface lights exhibited the increase of the radiance from January to May 2015 and the radiance was kept in the certain level to December 2016 with some variations. The ocean color, chlorophyll-a concentration as a proxy of sediments, showed an increase from February to June 2015 and returned to a low concentration in August 2015. According to the historical data of AIS, the number of dredgers has increased from February to August 2015 and the maximum number of dredgers was recorded in June 2015. The timing of increase of lights from surface, increase of chlorophyll-a concentration, and increase of number of vessels are consistent.
A prospective study of monitoring practices for metabolic disease in antipsychotic-treated community psychiatric patients
Paul Mackin, David R Bishop, Helen MO Watkinson
BMC Psychiatry , 2007, DOI: 10.1186/1471-244x-7-28
Abstract: We conducted a prospective cohort study of 106 community-treated psychiatric patients from across the diagnostic spectrum from the Northeast of England to investigate changes in metabolic status and monitoring practices for metabolic and cardiovascular disease. We undertook detailed anthropometric and metabolic assessment at baseline and follow-up, and examined clinical notes and hospital laboratory records to ascertain monitoring practices.A high prevalence of undiagnosed and untreated metabolic disease was present at baseline assessment. Mean follow-up time was 599.3 (SD ± 235.4) days. Body mass index (p < 0.005) and waist circumference (p < 0.05) had significantly increased at follow-up, as had the number of individuals who were either overweight or obese. Fifty-three per cent of individuals had hypertriglyceridemia, and 31% had hypercholesterolemia, but only 7% were receiving lipid-lowering therapy. Monitoring practices were poor. Recording of measures of adiposity occurred in 0% of individuals, and > 50% of subjects had neither blood glucose nor lipids monitored during the follow-up period.This cohort has a high prevalence of metabolic disease and heightened cardiovascular risk. Despite the publication of a number of recommendations regarding physical health screening in this population, monitoring rates are poor, and physical health worsened during the follow-up period.Severe mental illness (SMI) is associated with a significant excess of physical co-morbidity and mortality [1,2], and as such represents a major public health concern. Previous studies have reported a high prevalence of undiagnosed and untreated metabolic disorders and cardiovascular risk factors in patients with SMI [3-7]. Consensus statements from the US [8] and UK [9] have recommended stringent monitoring of metabolic status and cardiovascular risk factors in psychiatric patients receiving antipsychotic drugs, and recently published UK guidelines from the National Institute for Health and Cli
Different associations of white matter lesions with depression and cognition
Lee Jun-Young,Insel Philip,Mackin R,Schuff Norbert
BMC Neurology , 2012, DOI: 10.1186/1471-2377-12-83
Abstract: Background To test the hypothesis that white matter lesions (WML) are primarily associated with regional frontal cortical volumes, and to determine the mediating effects of these regional frontal cortices on the associations of WML with depressive symptoms and cognitive dysfunction. Methods Structural brains MRIs were performed on 161 participants: cognitively normal, cognitive impaired but not demented, and demented participants. Lobar WML volumes, regional frontal cortical volumes, depressive symptom severity, and cognitive abilities were measured. Multiple linear regression analyses were used to identify WML volume effects on frontal cortical volume. Structural equation modeling was used to determine the MRI-depression and the MRI-cognition path relationships. Results WML predicted frontal cortical volume, particularly in medial orbirtofrontal cortex, irrespective of age, gender, education, and group status. WML directly predicted depressive score, and this relationship was not mediated by regional frontal cortices. In contrast, the association between WML and cognitive function was indirect and mediated by regional frontal cortices. Conclusions These findings suggest that the neurobiological mechanisms underpinning depressive symptoms and cognitive dysfunction in older adults may differ.
Sleep disordered breathing in community psychiatric patients
Anderson,Kirstie N.; Waton,Tony; Armstrong,Daniel; Watkinson,Helen M.; Mackin,Paul;
The European Journal of Psychiatry , 2012, DOI: 10.4321/S0213-61632012000200002
Abstract: background and objectives: sleep disturbance is prominent in many neuropsychiatric disorders and may precipitate or exacerbate a range of psychiatric conditions. few studies have investigated sleep disordered breathing and in particular obstructive sleep apnoea in community psychiatric patients and the commonly used screening instruments have not been evaluated in patients with psychiatric disorders. the objective is to evaluate the prevalence of sleep disordered breathing in a community cohort with chronic mental illness on long term psychotropic medication, and to assess the effectiveness of commonly used screening instruments to detect abnormal sleep. methods: 52 patients completed sleep questionnaires and 50 undertook overnight oximetry. results: 52% (n = 26) had sleep-disordered breathing; 20% (n = 10) had moderate/severe sleep apnoea. the epworth sleepiness score and the pittsburgh sleep quality inventory did not predict sleep disordered breathing. conclusions: patients with psychiatric disorders in the community have a high rate of undiagnosed sleep disordered breathing, which is not reliably detected by established sleep disorder screening questionnaires.
Spo0A Differentially Regulates Toxin Production in Evolutionarily Diverse Strains of Clostridium difficile
Kate E. Mackin, Glen P. Carter, Pauline Howarth, Julian I. Rood, Dena Lyras
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0079666
Abstract: Clostridium difficile is an important pathogen of humans and animals, representing a significant global healthcare problem. The last decade has seen the emergence of epidemic BI/NAP1/027 and ribotype 078 isolates, associated with the onset of more severe disease and higher rates of morbidity and mortality. However, little is known about these isolates at the molecular level, partly due to difficulties in the genetic manipulation of these strains. Here we report the development of an optimised Tn916-mediated plasmid transfer system, and the use of this system to construct and complement spo0A mutants in a number of different C. difficile strain backgrounds. Spo0A is a global regulator known to control sporulation, but may also be involved in the regulation of potential virulence factors and other phenotypes. Recent studies have failed to elucidate the role of Spo0A in toxin A and toxin B production by C. difficile, with conflicting data published to date. In this study, we aimed to clarify the role of Spo0A in production of the major toxins by C. difficile. Through the construction and complementation of spo0A mutants in two ribotype 027 isolates, we demonstrate that Spo0A acts as a negative regulator of toxin A and toxin B production in this strain background. In addition, spo0A was disrupted and subsequently complemented in strain 630Δerm and, for the first time, in a ribotype 078 isolate, JGS6133. In contrast to the ribotype 027 strains, Spo0A does not appear to regulate toxin production in strain 630Δerm. In strain JGS6133, Spo0A appears to negatively regulate toxin production during early stationary phase, but has little effect on toxin expression during late stationary phase. These data suggest that Spo0A may differentially regulate toxin production in phylogenetically distinct C. difficile strain types. In addition, Spo0A may be involved in regulating some aspects of C. difficile motility.
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