Characterising the KMP-11 and HSP-70 recombinant antigens' humoral immune response profile in chagasic patients.

PubMed

Flechas, Ivonne D; Cuellar, Adriana; Cucunubá, Zulma M; Rosas, Fernando; Velasco, Víctor; Steindel, Mario; Thomas, María del Carmen; López, Manuel Carlos; González, John Mario; Puerta, Concepción Judith

2009-11-25

Antigen specificity and IgG subclass could be significant in the natural history of Chagas' disease. The relationship between the different stages of human Chagas' disease and the profiles of total IgG and its subclasses were thus analysed here; they were directed against a crude T. cruzi extract and three recombinant antigens: the T. cruzi kinetoplastid membrane protein-11 (rKMP-11), an internal fragment of the T. cruzi HSP-70 protein 192-433, and the entire Trypanosoma rangeli HSP-70 protein. Seventeen Brazilian acute chagasic patients, 50 Colombian chronic chagasic patients (21 indeterminate and 29 cardiopathic patients) and 30 healthy individuals were included. Total IgG and its subtypes directed against the above-mentioned recombinant antigens were determined by ELISA tests. The T. cruzi KMP-11 and T. rangeli HSP-70 recombinant proteins were able to distinguish both acute from chronic chagasic patients and infected people from healthy individuals. Specific antibodies to T. cruzi crude antigen in acute patients came from IgG3 and IgG4 subclasses whereas IgG1 and IgG3 were the prevalent isotypes in indeterminate and chronic chagasic patients. By contrast, the specific prominent antibodies in all disease stages against T. cruzi KMP-11 and T. rangeli HSP-70 recombinant antigens were the IgG1 subclass. T. cruzi KMP-11 and the T. rangeli HSP-70 recombinant proteins may be explored together in the immunodiagnosis of Chagas' disease. Polarising the IgG1 subclass of the IgG response to T. cruzi KMP-11 and T. rangeli HSP-70 recombinant proteins could have important biological effects, taking into account that this is a complement fixing antibody.

Probing Pre-Supernova Mass Loss With Circumstellar Dust Shells

NASA Astrophysics Data System (ADS)

Fox, Ori; Filippenko, Alex; Skrutskie, Mike; van Dyk, Schuyler; Kelly, Pat

2014-12-01

Late-time (>100 day) mid-infrared (mid-IR) observations of supernovae (SNe) offer a valuable probe of the progenitor system's mass-loss. Already, this technique has been demonstrated with the Type IIn subclass, which often have large, dusty, pre-existing shells formed in pre-SN eruptions. While other SN subclasses are thought of having relatively low density circumstellar environments, a growing number of objects in other subclasses now show evidence for significant pre-SN mass loss and similar mid-IR characteristics. Long after the SN radioactive tail fades, warm dust can stay bright at mid-IR wavelengths due to alternative heating mechanisms, such as shocks. Here we propose a SNAPSHOT survey of a well-studied and high-profile SN sample, extending over a range of subclasses, including both recent and historical events with evidence of a dense CSM and/or dust. This program will (a) discover new SNe with warm dust and (b) monitor the evolution of warm dust in previously detected SNe. Harnessing the success of our previous Spitzer programs, these observations will expand upon that work by probing the similarities in and differences between the subclasses' circumstellar environments, pre-SN mass-loss, and ultimately, the progenitors themselves.

Biophysical and Functional Characterization of Rhesus Macaque IgG Subclasses

PubMed Central

Boesch, Austin W.; Osei-Owusu, Nana Yaw; Crowley, Andrew R.; Chu, Thach H.; Chan, Ying N.; Weiner, Joshua A.; Bharadwaj, Pranay; Hards, Rufus; Adamo, Mark E.; Gerber, Scott A.; Cocklin, Sarah L.; Schmitz, Joern E.; Miles, Adam R.; Eckman, Joshua W.; Belli, Aaron J.; Reimann, Keith A.; Ackerman, Margaret E.

2016-01-01

Antibodies raised in Indian rhesus macaques [Macaca mulatta (MM)] in many preclinical vaccine studies are often evaluated in vitro for titer, antigen-recognition breadth, neutralization potency, and/or effector function, and in vivo for potential associations with protection. However, despite reliance on this key animal model in translation of promising candidate vaccines for evaluation in first in man studies, little is known about the properties of MM immunoglobulin G (IgG) subclasses and how they may compare to human IgG subclasses. Here, we evaluate the binding of MM IgG1, IgG2, IgG3, and IgG4 to human Fc gamma receptors (FcγR) and their ability to elicit the effector functions of human FcγR-bearing cells, and unlike in humans, find a notable absence of subclasses with dramatically silent Fc regions. Biophysical, in vitro, and in vivo characterization revealed MM IgG1 exhibited the greatest effector function activity followed by IgG2 and then IgG3/4. These findings in rhesus are in contrast with the canonical understanding that IgG1 and IgG3 dominate effector function in humans, indicating that subclass-switching profiles observed in rhesus studies may not strictly recapitulate those observed in human vaccine studies. PMID:28018355

Ligand Recognition by A-Class Eph Receptors: Crystal Structures of the EphA2 Ligand-Binding Domain and the EphA2/ephrin-A1 Complex

DOE Office of Scientific and Technical Information (OSTI.GOV)

Himanen, J.; Goldgur, Y; Miao, H

2009-01-01

Ephrin (Eph) receptor tyrosine kinases fall into two subclasses (A and B) according to preferences for their ephrin ligands. All published structural studies of Eph receptor/ephrin complexes involve B-class receptors. Here, we present the crystal structures of an A-class complex between EphA2 and ephrin-A1 and of unbound EphA2. Although these structures are similar overall to their B-class counterparts, they reveal important differences that define subclass specificity. The structures suggest that the A-class Eph receptor/ephrin interactions involve smaller rearrangements in the interacting partners, better described by a 'lock-and-key'-type binding mechanism, in contrast to the 'induced fit' mechanism defining the B-class molecules.more » This model is supported by structure-based mutagenesis and by differential requirements for ligand oligomerization by the two subclasses in cell-based Eph receptor activation assays. Finally, the structure of the unligated receptor reveals a homodimer assembly that might represent EphA2-specific homotypic cell adhesion interactions.« less

A quantitative ELISA for antigen-specific IgG subclasses using equivalence dilutions of anti-kappa and anti-subclass specific secondary reagents. Application to the study of the murine immune response against the capsular polysaccharide of Neisseria meningitidis serogroup B.

PubMed

Colino, J; Diez, M; Outschoorn, I

1996-04-19

We have developed an enzyme-linked immunosorbent assay (ELISA) to measure murine antigen-specific IgG antibodies of defined subclass using precalibrated equivalence dilutions of anti-kappa (in the standard) and each anti-IgG subclass-specific polyclonal secondary antibody (in the test sample). The calibration of secondary reagents could be carried out easily with a set of monoclonal antibodies (MoAbs) specific for all IgG subclasses. These MoAbs do not require purification or standardization. In addition the MoAbs can be of different antigenic specificity. Once the equivalence dilutions have been determined, they can be applied in a quantitative ELISA using the same antigen in the standard and sample, and using only one IgG subclass standard for the determination of all the IgG subclasses. The method is easy to standardize for many antigenic systems. It is particularly useful when the only standard available is one standardized MoAb of the appropriate specificity, and it could be adapted to use with standard polyclonal antibodies having a known content of total antigen-specific IgG bearing kappa chains but unknown IgG subclass composition. The use of this method to quantitate IgG specific for the capsular polysaccharide of Neisseria meningitidis serogroup B (CpsB) gave highly reproducible measures with an interbatch CV of 5-6% similar for all IgG subclasses and low detection limits ranging from 0.3 ng/well for IgG3 to 0.8 ng/well for IgG2a. The IgG subclass response observed after immunization with live meningococci was mainly IgG2a (74%) and IgG2b (18%). Hyperimmunization modified this IgG distribution to one of mainly IgG3 (62%) and IgG1 (28%) which was maintained in the response to a single immunization 4 weeks later, possibly indicating the generation of resting B cells during continuous stimulation.

FINAL ECOSYSTEM GOODS AND SERVICES CLASSIFICATION SYSTEM (FEGS-CS)

EPA Science Inventory

This document defines and classifies 338 Final Ecosystem Goods and Services (FEGS), each defined and uniquely numbered by a combination of environmental class or sub-class and a beneficiary category or sub-category. The introductory section provides the rationale and conceptual ...

Structural characterization of the Man5 glycoform of human IgG3 Fc

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shah, Ishan S.; Lovell, Scott; Mehzabeen, Nurjahan

Immunoglobulin G (IgG) consists of four subclasses in humans: IgG1, IgG2, IgG3 and IgG4, which are highly conserved but have unique differences that result in subclass-specific effector functions. Though IgG1 is the most extensively studied IgG subclass, study of other subclasses is important to understand overall immune function and for development of new therapeutics. When compared to IgG1, IgG3 exhibits a similar binding profile to Fcγ receptors and stronger activation of complement. All IgG subclasses are glycosylated at N297, which is required for Fcγ receptor and C1q complement binding as well as maintaining optimal Fc conformation. We have determined themore » crystal structure of homogenously glycosylated human IgG3 Fc with a GlcNAc2Man5 (Man5) high mannose glycoform at 1.8 Å resolution and compared its structural features with published structures from the other IgG subclasses. Although the overall structure of IgG3 Fc is similar to that of other subclasses, some structural perturbations based on sequence differences were revealed. For instance, the presence of R435 in IgG3 (and H435 in the other IgG subclasses) has been implicated to result in IgG3-specific properties related to binding to protein A, protein G and the neonatal Fc receptor (FcRn). The IgG3 Fc structure helps to explain some of these differences. Additionally, protein-glycan contacts observed in the crystal structure appear to correlate with IgG3 affinity for Fcγ receptors as shown by binding studies with IgG3 Fc glycoforms. Finally, this IgG3 Fc structure provides a template for further studies aimed at engineering the Fc for specific gain of function.« less

GE-29EXPRESSION SUBCLASS PROFILE IN PSEUDOPROGRESSION AND TRUE PROGRESSION IN NEWLY DIAGNOSED GBM

PubMed Central

Robin, Adam; Raghunathan, Aditya; Leung, Denise; Burmeister, Charlotte; Poisson, Laila; Scarpace, Lisa; Walbert, Tobias; Mikkelsen, Tom; Lee, Ian

2014-01-01

INTRODUCTION: The hallmark of glioblastoma multiforme (GBM) is its penchant for relentless progression. Pseudoprogression describes a post-treatment reaction demonstrating increased edema and contrast enhancement similar to typical tumor progression except that on subsequent imaging without escalation of antitumor therapy these changes stabilize or revert [1]. Accurate identification of pseudoprogression has important implications for therapy and research and potentially prognosis as well. Increased cellular proliferation (Ki-67 indices) and the presence of a methylated O-6-methylguanine-DNA methyltransferase (MGMT) promoter have been associated with higher rates of pseudoprogression [2,3]. However, more sensitive and specific biomarkers of pseudoprogression are needed. This study seeks to identify novel indicators of pseudoprogression. METHODS: Patients were identified using the Hermelin Brain Tumor Center database at Henry Ford Hospital. Tissues from 52 patients with newly diagnosed GBM between 1992 and 2011 were gathered and whole genome sequencing and subtyping was performed by The Cancer Genome Atlas researchers. Retrospective chart review was carried out. Patients were assigned to either pseudoprogression (PP) or true progression (TP) groups based on whether changes suggestive of disease progression on MRI within 2 months of post-operative therapy initiation regressed without additional antitumor therapy during the ensuing 4 months. The incidence of pseudoprogression and GBM subclass were correlated using Fisher's Exact Test. RESULTS: Forty-one of 52 (79%) cases were identified as TP while 11/52 (21%) were found to have PP. In our study population, PP was associated with significantly increased median survival compared with TP (735 versus 313 days, respectively, p < 0.0012). The molecular subclass profile for both groups included a predominance of Mesenchymal and Neural subtypes, revealing no correlation between GBM subclass and the risk of pseudoprogression (p < 0.8069). CONCLUSIONS: Pseudoprogression correlated with improved survival. Interestingly, Mesenchymal and Neural GBM subclasses predominated in our PP group, suggesting a factor independent of molecular subclassification may predict pseudoprogression.

Effects of Wheat and Oat-Based Whole Grain Foods on Serum Lipoprotein Size and Distribution in Overweight Middle Aged People: A Randomised Controlled Trial

PubMed Central

Tighe, Paula; Duthie, Garry; Brittenden, Julie; Vaughan, Nicholas; Mutch, William; Simpson, William G.; Duthie, Susan; Horgan, Graham W.; Thies, Frank

2013-01-01

Introduction Epidemiological studies suggest three daily servings of whole-grain foods (WGF) might lower cardiovascular disease risk, at least partly by lowering serum lipid levels. We have assessed the effects of consuming three daily portions of wholegrain food (provided as wheat or a mixture of wheat and oats) on lipoprotein subclass size and concentration in a dietary randomised controlled trial involving middle aged healthy individuals. Methods After a 4-week run-in period on a refined diet, volunteers were randomly allocated to a control (refined diet), wheat, or wheat + oats group for 12 weeks. Our servings were determined in order to significantly increase the intakes of non starch polysaccharides to the UK Dietary Reference Value of 18 g per day in the whole grain groups (18.5 g and 16.8 g per day in the wheat and wheat + oats groups respectively in comparison with 11.3 g per day in the control group). Outcome measures were serum lipoprotein subclasses' size and concentration. Habitual dietary intake was assessed prior and during the intervention. Of the 233 volunteers recruited, 24 withdrew and 3 were excluded. Results At baseline, significant associations were found between lipoprotein size and subclasses' concentrations and some markers of cardiovascular risk such as insulin resistance, blood pressure and serum Inter cellular adhesion molecule 1 concentration. Furthermore, alcohol and vitamin C intake were positively associated with an anti-atherogenic lipoprotein profile, with regards to lipoprotein size and subclasses' distribution. However, none of the interventions with whole grain affected lipoprotein size and profile. Conclusion Our results indicate that three portions of wholegrain foods, irrelevant of the type (wheat or oat-based) do not reduce cardiovascular risk by beneficially altering the size and distribution of lipoprotein subclasses. Trial Registration www.Controlled-Trials.com ISRCTN 27657880. PMID:23940575

High-density lipoprotein particle subclass heterogeneity and incident coronary heart disease.

PubMed

Akinkuolie, Akintunde O; Paynter, Nina P; Padmanabhan, Latha; Mora, Samia

2014-01-01

Raising the cholesterol of high-density lipoprotein (HDL) particles is targeted as a cardiovascular disease prevention strategy. However, HDL particles are heterogeneous in composition and structure, which may relate to differences in antiatherogenic potential. We prospectively evaluated the association of HDL subclasses, defined by a recently proposed nomenclature, with incident coronary heart disease (CHD). Baseline HDL particle concentrations were measured by nuclear magnetic resonance spectroscopy and categorized into 5 subclasses (very large, large, medium, small, and very small) among 26 332 initially healthy women. During a median follow-up of 17 years, 969 cases of incident CHD (myocardial infarction, revascularization, and CHD death) were ascertained. In Cox models that adjusted for age, race/ethnicity, blood pressure, smoking, postmenopausal status, and hormone therapy, associations with incident CHD were inverse (P trend<0.0001) for concentrations of very large (hazard ratio for top versus bottom quartile, 0.49; 95% confidence interval, 0.41-0.60), large (0.54; 0.45-0.64), and medium (0.69; 0.58-0.83) HDL subclasses. Conversely, hazard ratios (95% confidence intervals) for small and very small HDL were 1.22 (1.01-1.46; P trend=0.08) and 1.67 (1.39-2.02; P trend<0.0001), respectively. However, after additionally adjusting for metabolic and lipoprotein variables, associations for the spectrum of large, medium, and small HDL subclasses were inverse (P trend<0.05 for large and small and 0.07 for medium), whereas subclasses at either end of the spectrum were not associated with CHD (P trend=0.97 for very large and 0.21 for very small HDL). In this prospective study, associations with incident CHD differed by HDL particle subclass, which may be relevant for developing HDL-modulating therapies. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00000479.

Comparative expression analysis reveals lineage relationships between human and murine gliomas and a dominance of glial signatures during tumor propagation in vitro.

PubMed

Henriquez, Nico V; Forshew, Tim; Tatevossian, Ruth; Ellis, Matthew; Richard-Loendt, Angela; Rogers, Hazel; Jacques, Thomas S; Reitboeck, Pablo Garcia; Pearce, Kerra; Sheer, Denise; Grundy, Richard G; Brandner, Sebastian

2013-09-15

Brain tumors are thought to originate from stem/progenitor cell populations that acquire specific genetic mutations. Although current preclinical models have relevance to human pathogenesis, most do not recapitulate the histogenesis of the human disease. Recently, a large series of human gliomas and medulloblastomas were analyzed for genetic signatures of prognosis and therapeutic response. Using a mouse model system that generates three distinct types of intrinsic brain tumors, we correlated RNA and protein expression levels with human brain tumors. A combination of genetic mutations and cellular environment during tumor propagation defined the incidence and phenotype of intrinsic murine tumors. Importantly, in vitro passage of cancer stem cells uniformly promoted a glial expression profile in culture and in brain tumors. Gene expression profiling revealed that experimental gliomas corresponded to distinct subclasses of human glioblastoma, whereas experimental supratentorial primitive neuroectodermal tumors (sPNET) correspond to atypical teratoid/rhabdoid tumor (AT/RT), a rare childhood tumor. ©2013 AACR.

Site-Specific Expression of Polycomb-Group Genes Encoding the HPC-HPH/PRC1 Complex in Clinically Defined Primary Nodal and Cutaneous Large B-Cell Lymphomas

PubMed Central

Raaphorst, Frank M.; Vermeer, Maarten; Fieret, Elly; Blokzijl, Tjasso; Dukers, Danny; Sewalt, Richard G.A.B.; Otte, Arie P.; Willemze, Rein; Meijer, Chris J.L.M.

2004-01-01

Polycomb-group (PcG) genes preserve cell identity by gene silencing, and contribute to regulation of lymphopoiesis and malignant transformation. We show that primary nodal large B-cell lymphomas (LBCLs), and secondary cutaneous deposits from such lymphomas, abnormally express the BMI-1, RING1, and HPH1 PcG genes in cycling neoplastic cells. By contrast, tumor cells in primary cutaneous LBCLs lacked BMI-1 expression, whereas RING1 was variably detected. Lack of BMI-1 expression was characteristic for primary cutaneous LBCLs, because other primary extranodal LBCLs originating from brain, testes, and stomach were BMI-1-positive. Expression of HPH1 was rarely detected in primary cutaneous LBCLs of the head or trunk and abundant in primary cutaneous LBCLs of the legs, which fits well with its earlier recognition as a distinct clinical pathological entity with different clinical behavior. We conclude that clinically defined subclasses of primary LBCLs display site-specific abnormal expression patterns of PcG genes of the HPC-HPH/PRC1 PcG complex. Some of these patterns (such as the expression profile of BMI-1) may be diagnostically relevant. We propose that distinct expression profiles of PcG genes results in abnormal formation of HPC-HPH/PRC1 PcG complexes, and that this contributes to lymphomagenesis and different clinical behavior of clinically defined LBCLs. PMID:14742259

Integrated genetic and epigenetic analysis identifies three different subclasses of colon cancer

PubMed Central

Shen, Lanlan; Toyota, Minoru; Kondo, Yutaka; Lin, E; Zhang, Li; Guo, Yi; Hernandez, Natalie Supunpong; Chen, Xinli; Ahmed, Saira; Konishi, Kazuo; Hamilton, Stanley R.; Issa, Jean-Pierre J.

2007-01-01

Colon cancer has been viewed as the result of progressive accumulation of genetic and epigenetic abnormalities. However, this view does not fully reflect the molecular heterogeneity of the disease. We have analyzed both genetic (mutations of BRAF, KRAS, and p53 and microsatellite instability) and epigenetic alterations (DNA methylation of 27 CpG island promoter regions) in 97 primary colorectal cancer patients. Two clustering analyses on the basis of either epigenetic profiling or a combination of genetic and epigenetic profiling were performed to identify subclasses with distinct molecular signatures. Unsupervised hierarchical clustering of the DNA methylation data identified three distinct groups of colon cancers named CpG island methylator phenotype (CIMP) 1, CIMP2, and CIMP negative. Genetically, these three groups correspond to very distinct profiles. CIMP1 are characterized by MSI (80%) and BRAF mutations (53%) and rare KRAS and p53 mutations (16% and 11%, respectively). CIMP2 is associated with 92% KRAS mutations and rare MSI, BRAF, or p53 mutations (0, 4, and 31% respectively). CIMP-negative cases have a high rate of p53 mutations (71%) and lower rates of MSI (12%) or mutations of BRAF (2%) or KRAS (33%). Clustering based on both genetic and epigenetic parameters also identifies three distinct (and homogeneous) groups that largely overlap with the previous classification. The three groups are independent of age, gender, or stage, but CIMP1 and 2 are more common in proximal tumors. Together, our integrated genetic and epigenetic analysis reveals that colon cancers correspond to three molecularly distinct subclasses of disease. PMID:18003927

Subgroup-Elimination Transcriptomics Identifies Signaling Proteins that Define Subclasses of TRPV1-Positive Neurons and a Novel Paracrine Circuit

PubMed Central

Isensee, Jörg; Wenzel, Carsten; Buschow, Rene; Weissmann, Robert; Kuss, Andreas W.; Hucho, Tim

2014-01-01

Normal and painful stimuli are detected by specialized subgroups of peripheral sensory neurons. The understanding of the functional differences of each neuronal subgroup would be strongly enhanced by knowledge of the respective subgroup transcriptome. The separation of the subgroup of interest, however, has proven challenging as they can hardly be enriched. Instead of enriching, we now rapidly eliminated the subgroup of neurons expressing the heat-gated cation channel TRPV1 from dissociated rat sensory ganglia. Elimination was accomplished by brief treatment with TRPV1 agonists followed by the removal of compromised TRPV1(+) neurons using density centrifugation. By differential microarray and sequencing (RNA-Seq) based expression profiling we compared the transcriptome of all cells within sensory ganglia versus the same cells lacking TRPV1 expressing neurons, which revealed 240 differentially expressed genes (adj. p<0.05, fold-change>1.5). Corroborating the specificity of the approach, many of these genes have been reported to be involved in noxious heat or pain sensitization. Beyond the expected enrichment of ion channels, we found the TRPV1 transcriptome to be enriched for GPCRs and other signaling proteins involved in adenosine, calcium, and phosphatidylinositol signaling. Quantitative population analysis using a recent High Content Screening (HCS) microscopy approach identified substantial heterogeneity of expressed target proteins even within TRPV1-positive neurons. Signaling components defined distinct further subgroups within the population of TRPV1-positive neurons. Analysis of one such signaling system showed that the pain sensitizing prostaglandin PGD2 activates DP1 receptors expressed predominantly on TRPV1(+) neurons. In contrast, we found the PGD2 producing prostaglandin D synthase to be expressed exclusively in myelinated large-diameter neurons lacking TRPV1, which suggests a novel paracrine neuron-neuron communication. Thus, subgroup analysis based on the elimination rather than enrichment of the subgroup of interest revealed proteins that define subclasses of TRPV1-positive neurons and suggests a novel paracrine circuit. PMID:25551770

Whole-cell or acellular pertussis vaccination in infancy determines IgG subclass profiles to DTaP booster vaccination.

PubMed

van der Lee, Saskia; Sanders, Elisabeth A M; Berbers, Guy A M; Buisman, Anne-Marie

2018-01-04

Duration of protection against pertussis is shorter in adolescents who have been immunized with acellular pertussis (aP) in infancy compared with adolescents who received whole-cell pertussis (wP) vaccines in infancy, which is related to immune responses elicited by these priming vaccines. To better understand differences in vaccine induced immunity, we determined pertussis, diphtheria, and tetanus (DTaP) vaccine antigen-specific IgG subclass responses in wP- and aP-primed children before and after two successive DTaP booster vaccinations. Blood samples were collected in a cross-sectional study from wP- or aP-primed children before and 1 month after the pre-school DTaP booster vaccination at age 4 years. Blood samples were collected from two different wP- and aP-primed groups of children before, 1 month and 1 year after an additional pre-adolescent Tdap booster at age 9 years. IgG subclass levels against the antigens included in the DTaP vaccine have been determined with fluorescent-bead-based multiplex immunoassays. At 4 years of age, the IgG4 proportion and concentration for pertussis, diphtheria and tetanus vaccine antigens were significantly higher in aP-primed children compared with wP-primed children. IgG4 concentrations further increased upon the two successive booster vaccinations at 4 and 9 years of age in both wP- and aP-primed children, but remained significantly higher in aP-primed children. The pertussis vaccinations administered in the primary series at infancy determine the vaccine antigen-specific IgG subclass profiles, not only against the pertussis vaccine antigens, but also against the co-administered diphtheria and tetanus vaccine antigens. These profiles did not change after DTaP booster vaccinations later in childhood. The different immune response with high proportions of specific IgG4 in some aP-primed children may contribute to a reduced protection against pertussis. ISRCTN65428640; ISRCTN64117538; NTR4089. Copyright © 2017 Elsevier Ltd. All rights reserved.

Reliability of nine programs of topological predictions and their application to integral membrane channel and carrier proteins.

PubMed

Reddy, Abhinay; Cho, Jaehoon; Ling, Sam; Reddy, Vamsee; Shlykov, Maksim; Saier, Milton H

2014-01-01

We evaluated topological predictions for nine different programs, HMMTOP, TMHMM, SVMTOP, DAS, SOSUI, TOPCONS, PHOBIUS, MEMSAT-SVM (hereinafter referred to as MEMSAT), and SPOCTOPUS. These programs were first evaluated using four large topologically well-defined families of secondary transporters, and the three best programs were further evaluated using topologically more diverse families of channels and carriers. In the initial studies, the order of accuracy was: SPOCTOPUS > MEMSAT > HMMTOP > TOPCONS > PHOBIUS > TMHMM > SVMTOP > DAS > SOSUI. Some families, such as the Sugar Porter Family (2.A.1.1) of the Major Facilitator Superfamily (MFS; TC #2.A.1) and the Amino Acid/Polyamine/Organocation (APC) Family (TC #2.A.3), were correctly predicted with high accuracy while others, such as the Mitochondrial Carrier (MC) (TC #2.A.29) and the K(+) transporter (Trk) families (TC #2.A.38), were predicted with much lower accuracy. For small, topologically homogeneous families, SPOCTOPUS and MEMSAT were generally most reliable, while with large, more diverse superfamilies, HMMTOP often proved to have the greatest prediction accuracy. We next developed a novel program, TM-STATS, that tabulates HMMTOP, SPOCTOPUS or MEMSAT-based topological predictions for any subdivision (class, subclass, superfamily, family, subfamily, or any combination of these) of the Transporter Classification Database (TCDB; www.tcdb.org) and examined the following subclasses: α-type channel proteins (TC subclasses 1.A and 1.E), secreted pore-forming toxins (TC subclass 1.C) and secondary carriers (subclass 2.A). Histograms were generated for each of these subclasses, and the results were analyzed according to subclass, family and protein. The results provide an update of topological predictions for integral membrane transport proteins as well as guides for the development of more reliable topological prediction programs, taking family-specific characteristics into account. © 2014 S. Karger AG, Basel.

Variable beam dose rate and DMLC IMRT to moving body anatomy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Papiez, Lech; Abolfath, Ramin M.

2008-11-15

Derivation of formulas relating leaf speeds and beam dose rates for delivering planned intensity profiles to static and moving targets in dynamic multileaf collimator (DMLC) intensity modulated radiation therapy (IMRT) is presented. The analysis of equations determining algorithms for DMLC IMRT delivery under a variable beam dose rate reveals a multitude of possible delivery strategies for a given intensity map and for any given target motion patterns. From among all equivalent delivery strategies for DMLC IMRT treatments specific subclasses of strategies can be selected to provide deliveries that are particularly suitable for clinical applications providing existing delivery devices are used.more » Special attention is devoted to the subclass of beam dose rate variable DMLC delivery strategies to moving body anatomy that generalize existing techniques of such deliveries in Varian DMLC irradiation methodology to static body anatomy. Few examples of deliveries from this subclass of DMLC IMRT irradiations are investigated to illustrate the principle and show practical benefits of proposed techniques.« less

Antibody Profile of Colostrum and the Effect of Processing in Human Milk Banks: Implications in Immunoregulatory Properties.

PubMed

Rodríguez-Camejo, Claudio; Puyol, Arturo; Fazio, Laura; Rodríguez, Analía; Villamil, Emilia; Andina, Eliana; Cordobez, Vanira; Díaz, Hernán; Lemos, Mary; Siré, Gabriela; Carroscia, Lilián; Castro, Mara; Panizzolo, Luis; Hernández, Ana

2018-02-01

When feeding preterm infants, donor milk is preferred if the mother's own milk is unavailable. Pasteurization may have detrimental effects on bioactivity, but more information is needed about its effects on the immunological compounds. Research aim: This work has two main aims: evaluate the antibody profile of colostrum and study the quantitative variations in the antibodies' level and specific reactivity after undergoing Holder pasteurization. The authors focused on immunoregulatory components of colostrum (antidietary antibodies and TGF-β2) in the neonatal gut. This is a descriptive cross-sectional study of a convenience sample of 67 donated colostrum samples at different days after delivery, both raw and pasteurized. Antibody profiles were analyzed at different times during breastfeeding, and total and specific antibodies (IgM, IgA, and IgG subclasses) were compared with tetanus toxoid and ovalbumin using enzyme-linked immunosorbent assay. The processing effect on total and specific antibodies, as well as TGF-β2, was evaluated by paired analyses. No variations in immunological compounds were observed throughout the colostrum stage. The TGF-β2, antibodies' concentrations, and antibodies' specific reactivity after pasteurization did not vary significantly as days of lactation varied. Changes in antibody levels were dependent on isotype and IgG subclass, and IgG4 showed remarkable resistance to heating. Moreover, the effect of the pasteurization on specific reactivity was antigen dependent. The supply of relevant immunological components is stable throughout the colostrum stage. The effects of pasteurization on antibodies depend on isotype, subclass, and specificity. This information is relevant to improving the immunological quality of colostrum, especially for preterm newborns.

Gathering Real World Evidence with Cluster Analysis for Clinical Decision Support.

PubMed

Xia, Eryu; Liu, Haifeng; Li, Jing; Mei, Jing; Li, Xuejun; Xu, Enliang; Li, Xiang; Hu, Gang; Xie, Guotong; Xu, Meilin

2017-01-01

Clinical decision support systems are information technology systems that assist clinical decision-making tasks, which have been shown to enhance clinical performance. Cluster analysis, which groups similar patients together, aims to separate patient cases into phenotypically heterogenous groups and defining therapeutically homogeneous patient subclasses. Useful as it is, the application of cluster analysis in clinical decision support systems is less reported. Here, we describe the usage of cluster analysis in clinical decision support systems, by first dividing patient cases into similar groups and then providing diagnosis or treatment suggestions based on the group profiles. This integration provides data for clinical decisions and compiles a wide range of clinical practices to inform the performance of individual clinicians. We also include an example usage of the system under the scenario of blood lipid management in type 2 diabetes. These efforts represent a step toward promoting patient-centered care and enabling precision medicine.

Vaccine-Induced Env V1–V2 IgG3 Correlates with Lower HIV-1 Infection Risk and Declines Soon After Vaccination

PubMed Central

Yates, Nicole L.; Liao, Hua-Xin; Fong, Youyi; deCamp, Allan; Vandergrift, Nathan A.; Williams, William T.; Alam, S. Munir; Ferrari, Guido; Yang, Zhi-yong; Seaton, Kelly E.; Berman, Phillip W.; Alpert, Michael D.; Evans, David T.; O’Connell, Robert J.; Francis, Donald; Sinangil, Faruk; Lee, Carter; Nitayaphan, Sorachai; Rerks-Ngarm, Supachai; Kaewkungwal, Jaranit; Pitisuttithum, Punnee; Tartaglia, James; Pinter, Abraham; Zolla-Pazner, Susan; Gilbert, Peter B.; Nabel, Gary J.; Michael, Nelson L.; Kim, Jerome H.; Montefiori, David C.; Haynes, Barton F.; Tomaras, Georgia D.

2014-01-01

HIV-1–specific immunoglobulin G (IgG) subclass antibodies bind to distinct cellular Fc receptors. Antibodies of the same epitope specificity but of a different subclass therefore can have different antibody effector functions. The study of IgG subclass profiles between different vaccine regimens used in clinical trials with divergent efficacy outcomes can provide information on the quality of the vaccine-induced B cell response. We show that HIV-1–specific IgG3 distinguished two HIV-1 vaccine efficacy studies (RV144 and VAX003 clinical trials) and correlated with decreased risk of HIV-1 infection in a blinded follow-up case-control study with the RV144 vaccine. HIV-1–specific IgG3 responses were not long-lived, which was consistent with the waning efficacy of the RV144 vaccine. These data suggest that specific vaccine-induced HIV-1 IgG3 should be tested in future studies of immune correlates in HIV-1 vaccine efficacy trials. PMID:24648342

Phenotypic diversity of anthocyanins in sorghum accessions with various pericarp pigments

USDA-ARS?s Scientific Manuscript database

Anthocyanins, a sub-class of flavonoids, are natural pigments known to have functional health benefits. Sorghum is a rich source of various phytochemicals including anthocyanins. This study was to identify and quantify the profiles of anthocyanins by HPLC-DAD in the selected 25 sorghum accessions wi...

Why women use makeup: implication of psychological traits in makeup functions.

PubMed

Korichi, Rodolphe; Pelle-de-Queral, Delphine; Gazano, Germaine; Aubert, Arnaud

2008-01-01

Makeup acts and stimulates three of our senses: touch (which encompasses all sensations from the body surface), smell (fragrance), and sight (the process of becoming and looking beautiful). The positive stimulation of these senses by makeup can induce sensory as well as psychological pleasure. In order to understand the relationship of women to their makeup, we interviewed different groups of women on their quality of life and makeup habits. Then, through four standard well-validated psychometric self-questionnaires, we examined the possible relation between the need to make up oneself and specific psychological features. Our first results clearly showed that makeup could support two opposite "up" functions, i.e., "camouflage" vs "seduction." Concerning their psychological profiles, results showed that women of the functional class "camouflage" are more anxious, defensive, and emotionally unstable compared to those of the functional class "seduction," who appear to be more sociable, assertive, and extroverted. Further analyses revealed a division of the two classes into subclasses of volunteers with opposed personality and psychological profiles. This new classification allowed us to define more precisely the relations existing within the subjective experience of women during the makeup process. In conclusion, our study revealed that beyond the simple application of colorful products on the face, makeup has two major functional implications depending on specific psychological profiles of women.

Anti-food and anti-microbial IgG subclass antibodies in inflammatory bowel disease.

PubMed

Jansen, Anke; Mandić, Ana D; Bennek, Eveline; Frehn, Lisa; Verdier, Julien; Tebrügge, Irene; Lutz, Holger; Streetz, Konrad; Trautwein, Christian; Sellge, Gernot

2016-12-01

Inflammatory bowel disease (IBD), particularly Crohn's disease (CD), is associated with increased microbial-specific IgG and IgA antibodies, whereas alterations of anti-food antibodies are still disputed. The knowledge about IgG subclass antibodies in IBD is limited. In this study we analysed IgG subclass antibodies specific for nutritional and commensal antigens in IBD patients and controls. Serum IgG1, IgG2, IgG3 and IgG4 specific for wheat and milk extracts, purified ovalbumin, Escherichia coli and Bacteroides fragilis lysates and mannan from Saccharomyces cerevisiae were analysed by ELISA in patients with CD (n = 56), ulcerative colitis (UC; n = 29), acute gastroenteritis/colitis (n = 12) as well as non-inflammatory controls (n = 62). Anti-Saccharomyces cerevisiae antibodies (ASCA) of all IgG subclasses and anti-B. fragilis IgG1 levels were increased in CD patients compared to UC patients and controls. The discriminant validity of ASCA IgG2 and IgG4 was comparable with that of ASCA pan-IgG and IgA, whereas it was inferior for ASCA IgG1/IgG3 and anti-B. fragilis IgG1. Complicated CD defined by the presence of perianal, stricturing or penetrating disease phenotypes was associated with increased ASCA IgG1/IgG3/IgG4, anti-B. fragilis IgG1 and anti-E. coli IgG1 levels. Anti-food IgG subclass levels were not different between IBD patients and controls and did not correlate with food intolerance. In contrast to anti-microbial Abs, food-specific IgG responses were predominately of the IgG4 isotype and all food-specific IgG subclass levels correlated negatively with age. Our study supports the notion that the adaptive immune recognition of food and commensal antigens are differentially regulated.

Thyra Abstract Interface Package

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bartlett, Roscoe A.

2005-09-01

Thrya primarily defines a set of abstract C++ class interfaces needed for the development of abstract numerical atgorithms (ANAs) such as iterative linear solvers, transient solvers all the way up to optimization. At the foundation of these interfaces are abstract C++ classes for vectors, vector spaces, linear operators and multi-vectors. Also included in the Thyra package is C++ code for creating concrete vector, vector space, linear operator, and multi-vector subclasses as well as other utilities to aid in the development of ANAs. Currently, very general and efficient concrete subclass implementations exist for serial and SPMD in-core vectors and multi-vectors. Codemore » also currently exists for testing objects and providing composite objects such as product vectors.« less

Effects of Differing Response-Force Requirements on Food-Maintained Responding in C57BL/6J Mice

ERIC Educational Resources Information Center

Zarcone, Troy J.; Chen, Rong; Fowler, Stephen C.

2009-01-01

The effect of force requirements on response effort was examined using inbred C57BL/6J mice trained to press a disk with their snout. Lateral peak forces greater than 2 g were defined as responses (i.e., all responses above the measurement threshold). Different, higher force requirements were used to define criterion responses (a subclass of all…

Some properties for integro-differential operator defined by a fractional formal.

PubMed

Abdulnaby, Zainab E; Ibrahim, Rabha W; Kılıçman, Adem

2016-01-01

Recently, the study of the fractional formal (operators, polynomials and classes of special functions) has been increased. This study not only in mathematics but extended to another topics. In this effort, we investigate a generalized integro-differential operator [Formula: see text] defined by a fractional formal (fractional differential operator) and study some its geometric properties by employing it in new subclasses of analytic univalent functions.

A comparative study of the N-linked oligosaccharide structures of human IgG subclass proteins.

PubMed Central

Jefferis, R; Lund, J; Mizutani, H; Nakagawa, H; Kawazoe, Y; Arata, Y; Takahashi, N

1990-01-01

Quantitative oligosaccharide profiles were determined for each of 18 human IgG paraproteins representing the four subclasses. Each paraprotein exhibits a unique profile that may be substantially different from that observed for polyclonal IgG. The IgG2 and some IgG3 proteins analysed exhibit a predominance of oligosaccharide moieties having galactose on the Man(alpha 1----3) arm rather than the Man(alpha 1----6) arm; it was previously held that galactosylation of the Man(alpha 1----6) arm is preferred, as observed for IgG1, IgG4 and polyclonal IgG. An IgG4 protein is reported that has galactosylated Man(alpha 1----3) and Man(alpha 1----6) arms on both Fc-localized carbohydrate moieties; previous findings suggested that such fully glycosylated structures could not be accommodated within the internal space of the C gamma 2 domains. Unusual monoantennary oligosaccharides present in IgG2 and IgG3 proteins were isolated and their structures determined. Images Fig. 1. PMID:2363690

Defamation Issues in Higher Education.

ERIC Educational Resources Information Center

Bazluke, Francine Tilewick

This monograph reviews the law applying to defamation issues, cites various judicial decisions that affect colleges and universities, and offers guidance for minimizing the risk of defamation liability. It defines the two subclasses of defamatory statements: first, libel, which is a recorded or printed statement, and second, slander, which is…

48 CFR 211.275-2 - Policy.

Code of Federal Regulations, 2010 CFR

2010-10-01

... that— (1) Contain items in any of the following classes of supply, as defined in DoD 4140.1-R, DoD Supply Chain Materiel Management Regulation, AP1.1.11: (i) Subclass of Class I—Packaged operational... administrative and housekeeping supplies and equipment. (iii) Class IIIP—Packaged petroleum, lubricants, oils...

Frameshift Suppression in SACCHAROMYCES CEREVISIAE. IV. New Suppressors among Spontaneous Co-Revertants of the Group II HIS4-206 and LEU2-3 Frameshift Mutations

PubMed Central

Gaber, Richard F.; Culbertson, Michael R.

1982-01-01

ICR-induced frameshift mutations at the his4 locus in Saccharomyces cerevisiae have been classified into several groups on the basis of their reversion and suppression properties. One group of externally suppressible his4 mutations, designated Group II, have been shown to contain +1 G:C insertions in glycine codons and are suppressed by any one of five suppressor mutations described previously (SUF1, SUF3, SUF4, SUF5, and SUF6). The suppressor genes are believed to encode glycine tRNAs containing four base anticodons.—An analysis of spontaneous co-revertants of the Group II frameshift mutations his4-206 and leu2-3 has revealed the existence of eleven new Group II-specific suppressor genes (SUF15 through SUF25). The locations of the new suppressor loci on the yeast genetic map have been determined.—By comparing the ability or inability of Group II-specific suppressors mapping at 16 different loci to suppress different Group II his4 mutations, two subclasses of suppressors have been defined. One subclass suppresses his4-38 and his4-519, which contain the altered four base mRNA codons 5'-GGGU-3' and 5'-GGGG-3', respectively. The other subclass suppresses his4-38, but fails to suppress his4-519. The mechanism of tRNA-mediated frameshift suppression and the molecular basis for this division of the suppressors into two subclasses is discussed. PMID:6757051

Characterization and expression profiling of glutathione S-transferases in the diamondback moth, Plutella xylostella (L.).

PubMed

You, Yanchun; Xie, Miao; Ren, Nana; Cheng, Xuemin; Li, Jianyu; Ma, Xiaoli; Zou, Minming; Vasseur, Liette; Gurr, Geoff M; You, Minsheng

2015-03-05

Glutathione S-transferases (GSTs) are multifunctional detoxification enzymes that play important roles in insects. The completion of several insect genome projects has enabled the identification and characterization of GST genes over recent years. This study presents a genome-wide investigation of the diamondback moth (DBM), Plutella xylostella, a species in which the GSTs are of special importance because this pest is highly resistant to many insecticides. A total of 22 putative cytosolic GSTs were identified from a published P. xylostella genome and grouped into 6 subclasses (with two unclassified). Delta, Epsilon and Omega GSTs were numerically superior with 5 genes for each of the subclasses. The resulting phylogenetic tree showed that the P. xylostella GSTs were all clustered into Lepidoptera-specific branches. Intron sites and phases as well as GSH binding sites were strongly conserved within each of the subclasses in the GSTs of P. xylostella. Transcriptome-, RNA-seq- and qRT-PCR-based analyses showed that the GST genes were developmental stage- and strain-specifically expressed. Most of the highly expressed genes in insecticide resistant strains were also predominantly expressed in the Malpighian tubules, midgut or epidermis. To date, this is the most comprehensive study on genome-wide identification, characterization and expression profiling of the GST family in P. xylostella. The diversified features and expression patterns of the GSTs are inferred to be associated with the capacity of this species to develop resistance to a wide range of pesticides and biological toxins. Our findings provide a base for functional research on specific GST genes, a better understanding of the evolution of insecticide resistance, and strategies for more sustainable management of the pest.

Homographs: Classification and Identification.

ERIC Educational Resources Information Center

Pacak, M.; Henisz, Bozena

1968-01-01

Homographs are defined in this study as sets of word forms which are spelled alike but which have entirely or partially different meanings and which may have different syntactic functions (that is, they belong to more than one form class or to more than one subclass of a form class). This report deals with the classification and identification of…

Some classes of analytic functions involving Noor integral operator

NASA Astrophysics Data System (ADS)

Patel, J.; Cho, N. E.

2005-12-01

The object of the present paper is to investigate some inclusion properties of certain subclasses of analytic functions defined by using the Noor integral operator. The integral preserving properties in connection with the operator are also considered. Relevant connections of the results presented here with those obtained in earlier works are pointed out.

COLD CO GAS IN THE DISK OF THE YOUNG ERUPTIVE STAR EX LUP

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kóspál, Á.; Ábrahám, P.; Moór, A.

EX Lupi-type objects (EXors) form a sub-class of T Tauri stars, defined by sudden sporadic flare-ups of 1–5 mag at optical wavelengths. These eruptions are attributed to enhanced mass accretion from the circumstellar disk to the star, and may constitute important events in shaping the structure of the inner disk and the forming planetary system. Although disk properties must play a fundamental role in driving the outbursts, they are surprisingly poorly known. In order to characterize the dust and gas components of EXor disks, here we report on observations of the {sup 12}CO J = 3−2 and 4–3 lines, and themore » {sup 13}CO 3–2 line in EX Lup, the prototype of the EXor class. We reproduce the observed line fluxes and profiles with a line radiative transfer model and compare the obtained parameters with corresponding ones of other T Tauri disks.« less

The impact of chocolate on cardiovascular health.

PubMed

Fernández-Murga, L; Tarín, J J; García-Perez, M A; Cano, A

2011-08-01

Cardiovascular disease is the leading determinant of mortality and morbidity in women. Functional foods are attracting interest as potential regulators of the susceptibility to disease. Supported by epidemiological evidence, chocolate has emerged as a possible modulator of cardiovascular risk. Chocolate, or cocoa as the natural source, contains flavanols, a subclass of flavonoids. The latter years have witnessed an increasing number of experimental and clinical studies that suggest a protective effect of chocolate against atherogenesis. Oxidative stress, inflammation, and endothelial function define three biological mechanisms that have shown sensitivity to chocolate. Moreover, the consumption of chocolate has been involved in the protective modulation of blood pressure, the lipid profile, the activation of platelets, and the sensitivity to insulin. Dark chocolate seems more protective than milk or white chocolate. Despite this array of benefits, there is a lack of well designed clinical studies demonstrating cardiovascular benefit of chocolate. The high caloric content of chocolate, particularly of some less pure forms, imposes caution before recommending uncontrolled consumption. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Effect of Theobromine Consumption on Serum Lipoprotein Profiles in Apparently Healthy Humans with Low HDL-Cholesterol Concentrations

PubMed Central

Jacobs, Doris M.; Smolders, Lotte; Lin, Yuguang; de Roo, Niels; Trautwein, Elke A.; van Duynhoven, John; Mensink, Ronald P.; Plat, Jogchum; Mihaleva, Velitchka V.

2017-01-01

Scope: Theobromine is a major active compound in cocoa with allegedly beneficial effect on high-density-lipoprotein-cholesterol (HDL-CH). We have investigated the effect of theobromine (TB) consumption on the concentrations of triglyceride (TG) and cholesterol (CH) in various lipoprotein (LP) subclasses. Methods: In a randomized, double-blind, placebo-controlled, cross-over study, 44 apparently healthy women and men (age: 60 ± 6 years, BMI: 29 ± 3 kg/m2) with low baseline HDL-CH concentrations consumed a drink supplemented with 500 mg/d theobromine for 4 weeks. TG and CH concentrations in 15 LP subclasses were predicted from diffusion-edited 1H NMR spectra of fasting serum. Results: The LP phenotype of the subjects was characterized by low CH concentrations in the large HDL particles and high TG concentrations in large VLDL and chylomicron (CM) particles, which clearly differed from a LP phenotype of subjects with normal HDL-CH. TB only reduced CH concentrations in the LDL particles by 3.64 and 6.79%, but had no effect on TG and CH in any of the HDL, VLDL and CM subclasses. Conclusion: TB was not effective on HDL-CH in subjects with a LP phenotype characterized by low HDL-CH and high TG in VLDL. PMID:28971099

Does Kiitricha (Protista, Ciliophora, Spirotrichea) belong to Euplotida or represent a primordial spirotrichous taxon? With suggestion to establish a new subclass Protohypotrichia.

PubMed

Li, Lifang; Shao, Chen; Song, Weibo; Lynn, Denis H; Chen, Zigui; Shin, Mann Kyoon

2009-02-01

The genus Kiitricha was long assumed to be the most primordial taxon in the Stichotrichia [hypotrichs sensu lato (s. l.)] based on its morphological features and was considered to be an intermediate between heterotrichs and the traditional hypotrichous assemblage. In order to evaluate the phylogenetic position of Kiitricha within the Hypotrichia, we sequenced the small-subunit rRNA gene and the alpha-tubulin gene for a Qingdao population of Kiitricha marina. Phylogenetic trees were constructed and compared to morphological and morphogenetic data. The results show that (i) Kiitricha is positioned near Phacodinium, both of which always form a sister clade to the assemblage including Stichotrichia, Hypotrichia, Oligotrichia and Choreotrichia, (ii) Kiitricha, which may represent an intermediate between heterotrichs (s. l.) and the Stichotrichia-Hypotrichia complex, is probably an ancestor-like form of the latter group and (iii) in contrast to morphological characters, both molecular and ontogenetic data support the separation of Kiitricha from the hypotrichs (s. l.). Thus, Kiitricha might be placed in the class Spirotrichea at about subclass level, next to Phaconidiidia, Hypotrichia and Stichotrichia, which supports the establishment of a new subclass Protohypotrichia n. subclass within the class Spirotrichea, with characterizations including slightly differentiated somatic ciliature (i.e. cirri on the ventral side generally uniform and non-grouped, no clearly defined marginal cirral rows, ciliature on the dorsal side mixed with cirri and dikinetids, no clearly differentiated dorsal kineties) and a unique but intermediate morphogenetic pattern of cortical structures between Hypotrichia and Stichotrichia.

The floral biology of the Magnoliaceae

Treesearch

Leonard B. Thien; Shoichi Kawano; Hiroshi Azuma; Shane Latimer; Margaret S. Devall; Sam Rosso; Stella Elakovich; Victor Rico Gray; David Jobes

1996-01-01

The family Magnoliaceae, a well defined group of trees or shrubs, is a component of the order Magnoliales (subclass Magnoliidae) distributed in temperate (four-fifths of the species) and tropical Asia from the Himalayas eastward to Japan and southeastward through the Malay Archipelago to the New Guinea area (see map, Takhtajan 1969; Law 1984). The remainder of the...

The dependence on morphology of the gas content in galactic disks

NASA Technical Reports Server (NTRS)

Hogg, D. E.; Roberts, M. S.

1993-01-01

The classification S0 was introduced by Hubble to serve as a description of galaxies whose morphological characteristics seemed to lie between the disk-dominated spirals and the spheroidal elliptical systems. Since then there has been extensive discussion as to whether this classification sequence is also an evolutionary sequence. Many studies have focussed on a particular feature such as the luminosity profile, the bulge-to-disk ratio, or the nature of the interstellar matter, but the question of the evolution remains contentious. Equally contentious is the question of the classification itself. For systems with well-developed disks there usually is no problem. Many spheroidal systems also are unambiguously classified as ellipticals in most catalogs. However, there are a number of early systems which have been reclassified following review using improved optical material. For example, Eder et al. (AJ, 102, 572, 1991) found that many of the S0 galaxies which are rich in neutral hydrogen have faint spiral features. The confusion about classification propagates into the discussion of the properties of early-type systems. Attempts to put the classification system on a quantitative basis have in general been unsuccessful. Recently Sandage (private communication) has reviewed the classification of early systems and has defined a set of sub-classes for these objects. The S0 galaxies are divided into three groups, depending on the prominence of the disk. There are six subdivisions of Sa galaxies, depending upon the relative prominence of knots and other arm-like characteristics. We have explored the total gas content in these objects to see if there is a dependence on the galaxy morphology, as denoted by these new subclasses.

Molecular characterization and expression analysis of three subclasses of IgT in rainbow trout (Oncorhynchus mykiss)

PubMed Central

Zhang, Nu; Zhang, Xu-Jie; Chen, Dan-Dan; Sunyer, J. Oriol; Zhang, Yong-An

2017-01-01

As the teleost specific immunoglobulin, IgT plays important roles in systemic and mucosal immunity. In the current study, in rainbow trout, we have cloned the heavy chain (Igτ) genes of a secretory form of IgT2 as well as the membrane and secretory forms of a third IgT subclass, termed IgT3. Conserved cysteine and tryptophan residues that are crucial for the folding of the immunoglobulin domain as well as hydrophobic and hydrophilic residues within CART motif were identified in all IgT subclasses. Through analysis of the rainbow trout genome assembly, Igτ3 gene was found localized upstream of Igτ1 gene, while Igτ2 gene situated on another scaffold. At the transcriptional level, Igτ1 was mainly expressed in both systemic and mucosal lymphoid tissues, while Igτ2 was largely expressed in systemic lymphoid organs. After LPS and poly (I:C) treatment, Igτ1 and Igτ2 genes exhibited different expression profiles. Interestingly the transcriptional level of Igτ3 was negligible, although its protein product could be identified in trout serum. Importantly, a previously reported monoclonal antibody directed against trout IgT1 was able to recognize IgT2 and IgT3. These data demonstrate that there exist three subclasses of IgT in rainbow trout, and that their heavy chain genes display different expression patterns during stimulation. Overall, our data reflect the diversity and complexity of immunoglobulin in trout, thus provide a better understanding of the IgT system in the immune response of teleost fish. PMID:28062226

Ecology of southeastern shrub bogs (pocosins) and Carolina bays: a community profile

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sharitz, R.R.; Gibbons, J.W.

1982-11-01

Shrub bogs of the Southeast occur in areas of poorly developed internal drainage that typically but not always have highly developed organic or peat soils. Pocosins and Carolina bays are types or subclasses of shrub bogs on the coastal plains of the Carolinas and Georgia. They share roughly the same distribution patterns, soil types, floral and faunal species composition and other community attributes, but differ in geological formation. Carolina bays may contain pocosin as well as other communities, but are defined more by their unique elliptical shape and geomorphometry. The pocosin community is largely defined by its vegetation, a combinationmore » of a dense shrub understory and a sparser canopy. The community is part of a complex successional sequence of communities (sedge bogs, savannas, cedar bogs, and bay forests) that may be controlled by such factors as fire, hydroperiod, soil type, and peat depth. Pocosins and Carolina bays harbor a number of animal groups and may be locally important in their ecology. Although few species are endemic to these habitats, they may provide important refuges for a number of species. These communities are simultaneously among the least understood and most rapidly disappearing habitats of the Southeast. Forestry and agricultural clearage are current impacts.« less

Prediction and explanation in the multiverse

DOE Office of Scientific and Technical Information (OSTI.GOV)

Garriga, J.; Vilenkin, A.

2008-02-15

Probabilities in the multiverse can be calculated by assuming that we are typical representatives in a given reference class. But is this class well defined? What should be included in the ensemble in which we are supposed to be typical? There is a widespread belief that this question is inherently vague, and that there are various possible choices for the types of reference objects which should be counted in. Here we argue that the 'ideal' reference class (for the purpose of making predictions) can be defined unambiguously in a rather precise way, as the set of all observers with identicalmore » information content. When the observers in a given class perform an experiment, the class branches into subclasses who learn different information from the outcome of that experiment. The probabilities for the different outcomes are defined as the relative numbers of observers in each subclass. For practical purposes, wider reference classes can be used, where we trace over all information which is uncorrelated to the outcome of the experiment, or whose correlation with it is beyond our current understanding. We argue that, once we have gathered all practically available evidence, the optimal strategy for making predictions is to consider ourselves typical in any reference class we belong to, unless we have evidence to the contrary. In the latter case, the class must be correspondingly narrowed.« less

Effects of allergic diseases and age on the composition of serum IgG glycome in children

PubMed Central

Pezer, Marija; Stambuk, Jerko; Perica, Marija; Razdorov, Genadij; Banic, Ivana; Vuckovic, Frano; Gospic, Adrijana Miletic; Ugrina, Ivo; Vecenaj, Ana; Bakovic, Maja Pucic; Lokas, Sandra Bulat; Zivkovic, Jelena; Plavec, Davor; Devereux, Graham; Turkalj, Mirjana; Lauc, Gordan

2016-01-01

It is speculated that immunoglobulin G (IgG) plays a regulatory role in allergic reactions. The glycans on the Fc region are known to affect IgG effector functions, thereby possibly having a role in IgG modulation of allergic response. This is the first study investigating patients’ IgG glycosylation profile in allergic diseases. Subclass specific IgG glycosylation profile was analyzed in two cohorts of allergen sensitized and non-sensitized 3- to 11-year-old children (conducted at University of Aberdeen, UK and Children’s Hospital Srebrnjak, Zagreb, Croatia) with 893 subjects in total. IgG was isolated from serum/plasma by affinity chromatography on Protein G. IgG tryptic glycopeptides were analyzed by liquid chromatography electrospray ionization mass spectrometry. In the Zagreb cohort IgG glycome composition changed with age across all IgG subclasses. In both cohorts, IgG glycome composition did not differ in allergen sensitized subjects, nor children sensitized to individual allergens, single allergen mean wheal diameter or positive wheal sum values. In the Zagreb study the results were also replicated for high total serum IgE and in children with self-reported manifest allergic disease. In conclusion, our findings demonstrate no association between serum IgG glycome composition and allergic diseases in children. PMID:27616597

Land cover mapping of the National Park Service northwest Alaska management area using Landsat multispectral and thematic mapper satellite data

USGS Publications Warehouse

Markon, C.J.; Wesser, Sara

1998-01-01

A land cover map of the National Park Service northwest Alaska management area was produced using digitally processed Landsat data. These and other environmental data were incorporated into a geographic information system to provide baseline information about the nature and extent of resources present in this northwest Alaskan environment.This report details the methodology, depicts vegetation profiles of the surrounding landscape, and describes the different vegetation types mapped. Portions of nine Landsat satellite (multispectral scanner and thematic mapper) scenes were used to produce a land cover map of the Cape Krusenstern National Monument and Noatak National Preserve and to update an existing land cover map of Kobuk Valley National Park Valley National Park. A Bayesian multivariate classifier was applied to the multispectral data sets, followed by the application of ancillary data (elevation, slope, aspect, soils, watersheds, and geology) to enhance the spectral separation of classes into more meaningful vegetation types. The resulting land cover map contains six major land cover categories (forest, shrub, herbaceous, sparse/barren, water, other) and 19 subclasses encompassing 7 million hectares. General narratives of the distribution of the subclasses throughout the project area are given along with vegetation profiles showing common relationships between topographic gradients and vegetation communities.

Investigation of trophic ecology in Newfoundland cold-water deep-sea corals using lipid class and fatty acid analyses

NASA Astrophysics Data System (ADS)

Salvo, Flora; Hamoutene, Dounia; Hayes, Vonda E. Wareham; Edinger, Evan N.; Parrish, Christopher C.

2018-03-01

The trophic behavior of some deep-sea Newfoundland cold-water corals was explored using fatty acid (FA) and lipid profiles. No significant effect of geographic location and/or depth was identified in lipid or FA composition. However, differences were detected between and within taxon groups in hexa- or octocoral subclasses. Phospholipids constituted the main lipid class in all groups except black-thorny corals which had less structural lipids likely due to their morphology (stiff axes) and slower growth rates. Within each subclass, major differences in the identity of dominant FAs were detected at the order level, whereas differences between species and taxon groups of the same order were mainly driven by a variation in proportions of the dominant FA. Soft corals and gorgonians (Order Alcyonacea) were close in composition and are likely relying on phytodetritus resulting from algae, macrophytes and/or foraminifera, while sea pens (Order Pennatulacea) seem to consume more diatoms and/or herbivorous zooplankton with the exception of Pennatula sp. In the hexacoral subclass, black-thorny corals ( Stauropathes arctica) differed significantly from the stony-cup corals ( Flabellum alabastrum); S. arctica was seemingly more carnivorous (zooplankton markers) than F. alabastrum, which appears omnivorous (phyto- and zooplankton markers). Our results suggest that deep-sea corals are not as opportunistic as expected but have some selective feeding associated with taxonomy.

Quantitative measurement of human thyroglobulin-specific antibodies by use of a sensitive enzyme-linked immunoassay.

PubMed

Kuppers, R C; Outschoorn, I M; Hamilton, R G; Burek, C L; Rose, N R

1993-04-01

A quantitative enzyme-linked immunoassay that measures in absolute terms the subclass concentration of human thyroglobulin (huTg)-specific IgG autoantibody was developed. Unique to this study was the use of an affinity-purified anti-huTg standard with a known concentration of the four IgG subclasses. The sensitivity of the ELISA assay was 1-5 ng/ml depending on the IgG subclass being measured. We examined 22 sera of patients with autoimmune thyroid disease. The total huTg-specific antibody concentrations in serum ranged from 0 to nearly 3000 micrograms/ml of IgG. The IgG subclass distribution in individuals with low huTg-specific IgG (< 10 micrograms/ml) was primarily IgG1 and IgG3 Ab. Patients with intermediate levels of huTg IgG (10-600 micrograms/ml) expressed all four subclasses; however, no particular subclass was dominant. Individuals with > 1000 micrograms/ml also showed huTg-Ab in all four subclasses, however, IgG1 and IgG2 were dominant. All four IgG subclasses were used in the response to huTg, although the pattern of usage varied between individuals. There was no dominant subclass usage seen in this patient population.

StrateGene: object-oriented programming in molecular biology.

PubMed

Carhart, R E; Cash, H D; Moore, J F

1988-03-01

This paper describes some of the ways that object-oriented programming methodologies have been used to represent and manipulate biological information in a working application. When running on a Xerox 1100 series computer, StrateGene functions as a genetic engineering workstation for the management of information about cloning experiments. It represents biological molecules, enzymes, fragments, and methods as classes, subclasses, and members in a hierarchy of objects. These objects may have various attributes, which themselves can be defined and classified. The attributes and their values can be passed from the classes of objects down to the subclasses and members. The user can modify the objects and their attributes while using them. New knowledge and changes to the system can be incorporated relatively easily. The operations on the biological objects are associated with the objects themselves. This makes it easier to invoke them correctly and allows generic operations to be customized for the particular object.

On Maximal Hard-Core Thinnings of Stationary Particle Processes

NASA Astrophysics Data System (ADS)

Hirsch, Christian; Last, Günter

2018-02-01

The present paper studies existence and distributional uniqueness of subclasses of stationary hard-core particle systems arising as thinnings of stationary particle processes. These subclasses are defined by natural maximality criteria. We investigate two specific criteria, one related to the intensity of the hard-core particle process, the other one being a local optimality criterion on the level of realizations. In fact, the criteria are equivalent under suitable moment conditions. We show that stationary hard-core thinnings satisfying such criteria exist and are frequently distributionally unique. More precisely, distributional uniqueness holds in subcritical and barely supercritical regimes of continuum percolation. Additionally, based on the analysis of a specific example, we argue that fluctuations in grain sizes can play an important role for establishing distributional uniqueness at high intensities. Finally, we provide a family of algorithmically constructible approximations whose volume fractions are arbitrarily close to the maximum.

NKL homeobox gene activities in hematopoietic stem cells, T-cell development and T-cell leukemia.

PubMed

Nagel, Stefan; Pommerenke, Claudia; Scherr, Michaela; Meyer, Corinna; Kaufmann, Maren; Battmer, Karin; MacLeod, Roderick A F; Drexler, Hans G

2017-01-01

T-cell acute lymphoblastic leukemia (T-ALL) cells represent developmentally arrested T-cell progenitors, subsets of which aberrantly express homeobox genes of the NKL subclass, including TLX1, TLX3, NKX2-1, NKX2-5, NKX3-1 and MSX1. Here, we analyzed the transcriptional landscape of all 48 members of the NKL homeobox gene subclass in CD34+ hematopoietic stem and progenitor cells (HSPCs) and during lymphopoiesis, identifying activities of nine particular genes. Four of these were expressed in HSPCs (HHEX, HLX1, NKX2-3 and NKX3-1) and three in common lymphoid progenitors (HHEX, HLX1 and MSX1). Interestingly, our data indicated downregulation of NKL homeobox gene transcripts in late progenitors and mature T-cells, a phenomenon which might explain the oncogenic impact of this group of genes in T-ALL. Using MSX1-expressing T-ALL cell lines as models, we showed that HHEX activates while HLX1, NKX2-3 and NKX3-1 repress MSX1 transcription, demonstrating the mutual regulation and differential activities of these homeobox genes. Analysis of a public T-ALL expression profiling data set comprising 117 patient samples identified 20 aberrantly activated members of the NKL subclass, extending the number of known NKL homeobox oncogene candidates. While 7/20 genes were also active during hematopoiesis, the remaining 13 showed ectopic expression. Finally, comparative analyses of T-ALL patient and cell line profiling data of NKL-positive and NKL-negative samples indicated absence of shared target genes but instead highlighted deregulation of apoptosis as common oncogenic effect. Taken together, we present a comprehensive survey of NKL homeobox genes in early hematopoiesis, T-cell development and T-ALL, showing that these genes generate an NKL-code for the diverse stages of lymphoid development which might be fundamental for regular differentiation.

NKL homeobox gene activities in hematopoietic stem cells, T-cell development and T-cell leukemia

PubMed Central

Pommerenke, Claudia; Scherr, Michaela; Meyer, Corinna; Kaufmann, Maren; Battmer, Karin; MacLeod, Roderick A. F.; Drexler, Hans G.

2017-01-01

T-cell acute lymphoblastic leukemia (T-ALL) cells represent developmentally arrested T-cell progenitors, subsets of which aberrantly express homeobox genes of the NKL subclass, including TLX1, TLX3, NKX2-1, NKX2-5, NKX3-1 and MSX1. Here, we analyzed the transcriptional landscape of all 48 members of the NKL homeobox gene subclass in CD34+ hematopoietic stem and progenitor cells (HSPCs) and during lymphopoiesis, identifying activities of nine particular genes. Four of these were expressed in HSPCs (HHEX, HLX1, NKX2-3 and NKX3-1) and three in common lymphoid progenitors (HHEX, HLX1 and MSX1). Interestingly, our data indicated downregulation of NKL homeobox gene transcripts in late progenitors and mature T-cells, a phenomenon which might explain the oncogenic impact of this group of genes in T-ALL. Using MSX1-expressing T-ALL cell lines as models, we showed that HHEX activates while HLX1, NKX2-3 and NKX3-1 repress MSX1 transcription, demonstrating the mutual regulation and differential activities of these homeobox genes. Analysis of a public T-ALL expression profiling data set comprising 117 patient samples identified 20 aberrantly activated members of the NKL subclass, extending the number of known NKL homeobox oncogene candidates. While 7/20 genes were also active during hematopoiesis, the remaining 13 showed ectopic expression. Finally, comparative analyses of T-ALL patient and cell line profiling data of NKL-positive and NKL-negative samples indicated absence of shared target genes but instead highlighted deregulation of apoptosis as common oncogenic effect. Taken together, we present a comprehensive survey of NKL homeobox genes in early hematopoiesis, T-cell development and T-ALL, showing that these genes generate an NKL-code for the diverse stages of lymphoid development which might be fundamental for regular differentiation. PMID:28151996

Wood particleboard and flakeboard : types, grades, and uses

Treesearch

C. G. Carll

1986-01-01

This report is for those who use or may want to use wood particleboard. The term bparticleboardc is used as defined in the American Society for Testing and Materials (ASTM) Standard D 1554, which includes flakeboards as a subclass of particleboards, and not as used in the lumber trade where the term is usually reserved for panels made of fine wood particles such as...

Change-in-ratio estimators for populations with more than two subclasses

USGS Publications Warehouse

Udevitz, Mark S.; Pollock, Kenneth H.

1991-01-01

Change-in-ratio methods have been developed to estimate the size of populations with two or three population subclasses. Most of these methods require the often unreasonable assumption of equal sampling probabilities for individuals in all subclasses. This paper presents new models based on the weaker assumption that ratios of sampling probabilities are constant over time for populations with three or more subclasses. Estimation under these models requires that a value be assumed for one of these ratios when there are two samples. Explicit expressions are given for the maximum likelihood estimators under models for two samples with three or more subclasses and for three samples with two subclasses. A numerical method using readily available statistical software is described for obtaining the estimators and their standard errors under all of the models. Likelihood ratio tests that can be used in model selection are discussed. Emphasis is on the two-sample, three-subclass models for which Monte-Carlo simulation results and an illustrative example are presented.

A scheme for a flexible classification of dietary and health biomarkers.

PubMed

Gao, Qian; Praticò, Giulia; Scalbert, Augustin; Vergères, Guy; Kolehmainen, Marjukka; Manach, Claudine; Brennan, Lorraine; Afman, Lydia A; Wishart, David S; Andres-Lacueva, Cristina; Garcia-Aloy, Mar; Verhagen, Hans; Feskens, Edith J M; Dragsted, Lars O

2017-01-01

Biomarkers are an efficient means to examine intakes or exposures and their biological effects and to assess system susceptibility. Aided by novel profiling technologies, the biomarker research field is undergoing rapid development and new putative biomarkers are continuously emerging in the scientific literature. However, the existing concepts for classification of biomarkers in the dietary and health area may be ambiguous, leading to uncertainty about their application. In order to better understand the potential of biomarkers and to communicate their use and application, it is imperative to have a solid scheme for biomarker classification that will provide a well-defined ontology for the field. In this manuscript, we provide an improved scheme for biomarker classification based on their intended use rather than the technology or outcomes (six subclasses are suggested: food compound intake biomarkers (FCIBs), food or food component intake biomarkers (FIBs), dietary pattern biomarkers (DPBs), food compound status biomarkers (FCSBs), effect biomarkers, physiological or health state biomarkers). The application of this scheme is described in detail for the dietary and health area and is compared with previous biomarker classification for this field of research.

Gene expression profiling at birth characterizing the preterm infant with early onset infection.

PubMed

Hilgendorff, Anne; Windhorst, Anita; Klein, Manuel; Tchatalbachev, Svetlin; Windemuth-Kieselbach, Christine; Kreuder, Joachim; Heckmann, Matthias; Gkatzoflia, Anna; Ehrhardt, Harald; Mysliwietz, Josef; Maier, Michael; Izar, Benjamin; Billion, Andre; Gortner, Ludwig; Chakraborty, Trinad; Hossain, Hamid

2017-02-01

Early onset infection (EOI) in preterm infants <32 weeks gestational age (GA) is associated with a high mortality rate and the development of severe acute and long-term complications. The pathophysiology of EOI is not fully understood and clinical and laboratory signs of early onset infections in this patient cohort are often not conclusive. Thus, the aim of this study was to identify signatures characterizing preterm infants with EOI by using genome-wide gene expression (GWGE) analyses from umbilical arterial blood of preterm infants. This prospective cohort study was conducted in preterm infants <32 weeks GA. GWGE analyses using CodeLink human microarrays were performed from umbilical arterial blood of preterm infants with and without EOI. GWGE analyses revealed differential expression of 292 genes in preterm infants with EOI as compared to infants without EOI. Infants with EOI could be further differentiated into two subclasses and were distinguished by the magnitude of the expression of genes involved in both neutrophil and T cell activation. A hallmark activity for both subclasses of EOI was a common suppression of genes involved in natural killer (NK) cell function, which was independent from NK cell numbers. Significant results were recapitulated in an independent validation cohort. Gene expression profiling may enable early and more precise diagnosis of EOI in preterm infants. Gene expression (GE) profiling at birth characterizes preterm infants with EOI. GE analysis indicates dysregulation of NK cell activity. NK cell activity at birth may be a useful marker to improve early diagnosis of EOI.

Analysing grouping of nucleotides in DNA sequences using lumped processes constructed from Markov chains.

PubMed

Guédon, Yann; d'Aubenton-Carafa, Yves; Thermes, Claude

2006-03-01

The most commonly used models for analysing local dependencies in DNA sequences are (high-order) Markov chains. Incorporating knowledge relative to the possible grouping of the nucleotides enables to define dedicated sub-classes of Markov chains. The problem of formulating lumpability hypotheses for a Markov chain is therefore addressed. In the classical approach to lumpability, this problem can be formulated as the determination of an appropriate state space (smaller than the original state space) such that the lumped chain defined on this state space retains the Markov property. We propose a different perspective on lumpability where the state space is fixed and the partitioning of this state space is represented by a one-to-many probabilistic function within a two-level stochastic process. Three nested classes of lumped processes can be defined in this way as sub-classes of first-order Markov chains. These lumped processes enable parsimonious reparameterizations of Markov chains that help to reveal relevant partitions of the state space. Characterizations of the lumped processes on the original transition probability matrix are derived. Different model selection methods relying either on hypothesis testing or on penalized log-likelihood criteria are presented as well as extensions to lumped processes constructed from high-order Markov chains. The relevance of the proposed approach to lumpability is illustrated by the analysis of DNA sequences. In particular, the use of lumped processes enables to highlight differences between intronic sequences and gene untranslated region sequences.

Natural and technical factors in faecal contamination incidents of drinking water in small distribution networks, France, 2003-2004: a geographical study.

PubMed

Beaudeau, Pascal; Valdes, Danièle; Mouly, Damien; Stempfelet, Morgane; Seux, René

2010-03-01

This geographical study aimed to show natural or water-processing-related factors of faecal contamination incidents (FCIs) of drinking water in continental France. We defined a FCI as the occurrence of at least 20 colony-forming Escherichia coli or enterococci among all the 100 mL samples collected for regulatory purpose within one day from a given drinking water supply zone (SZ). We explored correlations between the standardized number of FCIs per département (N_Pols) and various indicators related to weather, land cover, topography, geology and water management for three SZ size sub-classes. In 2003-2004, 2,739 FCIs occurred in SZs supplying fewer than 2,000 people, mainly with simply disinfected groundwater. N_Pols correlates with four covariates: (1) precipitation; (2) the extension of the karst outcrops; (3) the extent of disinfection; and (4) catchment protection. One hundred millimetres of yearly excess in precipitation increases the pollution risk by 28-37%, depending on the sub-class. A 10% extension of the karst areas, a 10% increase of unprotected resources, or of SZs with no disinfection, could entail a higher risk of FCI by about 10%. The correlations are reproducible over the three sub-classes and corroborate expert appraisals. These results encourage the ongoing effort to generalize disinfection and catchment protection.

Fox gene loci in Takifugu rubripes and Tetraodon nigroviridis genomes and comparison with those of medaka and zebrafish genomes.

PubMed

Shen, Xueyan; Cui, Jianzhou; Gong, Qingli

2011-12-01

Members of the Fox gene family of transcriptional regulators are essential for animal development and have been extensively studied in vertebrates. The mouse and human genomes contain at least 40 FOX genes which are divided into 19 subclasses based on the sequence similarity of the highly conserved forkhead domain. Using the genome sequence of the Takifugu rubripes and Tetraodon nigroviridis , we examined the genomic complement of fox genes in these organisms to gain insight into the evolutionary relationship of this gene family. We identified 53 fox genes in Tetraodon nigroviridis and Takifugu rubripes genome by searching the forkhead domain. These genes are divided into 18 subclasses as follows: 8 fox genes in subclass O; 6 in subclass P ; 4 in subclasses D, J, and N; 3 in subclasses A, B, C, E, F, and I; 2 in subclasses K, L, and Q; and 1 in subclasses G, H, M, and R. Together with the forkhead domain sequences of human, chicken, frog, zebrafish, medaka, and Caenorhabditis elegans, the phylogenetic relationship of the fox genes in Takifugu rubripes and Tetraodon nigroviridis were analyzed and compared. The genes structure, general features, and the three-dimensional model of these genes were also discussed.

Association of branched-chain amino acids and other circulating metabolites with risk of incident dementia and Alzheimer's disease: A prospective study in eight cohorts.

PubMed

Tynkkynen, Juho; Chouraki, Vincent; van der Lee, Sven J; Hernesniemi, Jussi; Yang, Qiong; Li, Shuo; Beiser, Alexa; Larson, Martin G; Sääksjärvi, Katri; Shipley, Martin J; Singh-Manoux, Archana; Gerszten, Robert E; Wang, Thomas J; Havulinna, Aki S; Würtz, Peter; Fischer, Krista; Demirkan, Ayse; Ikram, M Arfan; Amin, Najaf; Lehtimäki, Terho; Kähönen, Mika; Perola, Markus; Metspalu, Andres; Kangas, Antti J; Soininen, Pasi; Ala-Korpela, Mika; Vasan, Ramachandran S; Kivimäki, Mika; van Duijn, Cornelia M; Seshadri, Sudha; Salomaa, Veikko

2018-06-01

Metabolite, lipid, and lipoprotein lipid profiling can provide novel insights into mechanisms underlying incident dementia and Alzheimer's disease. We studied eight prospective cohorts with 22,623 participants profiled by nuclear magnetic resonance or mass spectrometry metabolomics. Four cohorts were used for discovery with replication undertaken in the other four to avoid false positives. For metabolites that survived replication, combined association results are presented. Over 246,698 person-years, 995 and 745 cases of incident dementia and Alzheimer's disease were detected, respectively. Three branched-chain amino acids (isoleucine, leucine, and valine), creatinine and two very low density lipoprotein (VLDL)-specific lipoprotein lipid subclasses were associated with lower dementia risk. One high density lipoprotein (HDL; the concentration of cholesterol esters relative to total lipids in large HDL) and one VLDL (total cholesterol to total lipids ratio in very large VLDL) lipoprotein lipid subclass was associated with increased dementia risk. Branched-chain amino acids were also associated with decreased Alzheimer's disease risk and the concentration of cholesterol esters relative to total lipids in large HDL with increased Alzheimer's disease risk. Further studies can clarify whether these molecules play a causal role in dementia pathogenesis or are merely markers of early pathology. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Glioma IL13Rα2 Is Associated with Mesenchymal Signature Gene Expression and Poor Patient Prognosis

PubMed Central

Starr, Renate; Deng, Xutao; Badie, Behnam; Yuan, Yate-Ching; Forman, Stephen J.; Barish, Michael E.

2013-01-01

A major challenge for successful immunotherapy against glioma is the identification and characterization of validated targets. We have taken a bioinformatics approach towards understanding the biological context of IL-13 receptor α2 (IL13Rα2) expression in brain tumors, and its functional significance for patient survival. Querying multiple gene expression databases, we show that IL13Rα2 expression increases with glioma malignancy grade, and expression for high-grade tumors is bimodal, with approximately 58% of WHO grade IV gliomas over-expressing this receptor. By several measures, IL13Rα2 expression in patient samples and low-passage primary glioma lines most consistently correlates with the expression of signature genes defining mesenchymal subclass tumors and negatively correlates with proneural signature genes as defined by two studies. Positive associations were also noted with proliferative signature genes, whereas no consistent associations were found with either classical or neural signature genes. Probing the potential functional consequences of this mesenchymal association through IPA analysis suggests that IL13Rα2 expression is associated with activation of proinflammatory and immune pathways characteristic of mesenchymal subclass tumors. In addition, survival analyses indicate that IL13Rα2 over-expression is associated with poor patient prognosis, a single gene correlation ranking IL13Rα2 in the top ~1% of total gene expression probes with regard to survival association with WHO IV gliomas. This study better defines the functional consequences of IL13Rα2 expression by demonstrating association with mesenchymal signature gene expression and poor patient prognosis. It thus highlights the utility of IL13Rα2 as a therapeutic target, and helps define patient populations most likely to respond to immunotherapy in present and future clinical trials. PMID:24204956

Glioma IL13Rα2 is associated with mesenchymal signature gene expression and poor patient prognosis.

PubMed

Brown, Christine E; Warden, Charles D; Starr, Renate; Deng, Xutao; Badie, Behnam; Yuan, Yate-Ching; Forman, Stephen J; Barish, Michael E

2013-01-01

A major challenge for successful immunotherapy against glioma is the identification and characterization of validated targets. We have taken a bioinformatics approach towards understanding the biological context of IL-13 receptor α2 (IL13Rα2) expression in brain tumors, and its functional significance for patient survival. Querying multiple gene expression databases, we show that IL13Rα2 expression increases with glioma malignancy grade, and expression for high-grade tumors is bimodal, with approximately 58% of WHO grade IV gliomas over-expressing this receptor. By several measures, IL13Rα2 expression in patient samples and low-passage primary glioma lines most consistently correlates with the expression of signature genes defining mesenchymal subclass tumors and negatively correlates with proneural signature genes as defined by two studies. Positive associations were also noted with proliferative signature genes, whereas no consistent associations were found with either classical or neural signature genes. Probing the potential functional consequences of this mesenchymal association through IPA analysis suggests that IL13Rα2 expression is associated with activation of proinflammatory and immune pathways characteristic of mesenchymal subclass tumors. In addition, survival analyses indicate that IL13Rα2 over-expression is associated with poor patient prognosis, a single gene correlation ranking IL13Rα2 in the top ~1% of total gene expression probes with regard to survival association with WHO IV gliomas. This study better defines the functional consequences of IL13Rα2 expression by demonstrating association with mesenchymal signature gene expression and poor patient prognosis. It thus highlights the utility of IL13Rα2 as a therapeutic target, and helps define patient populations most likely to respond to immunotherapy in present and future clinical trials.

Automated cell-type classification in intact tissues by single-cell molecular profiling

PubMed Central

2018-01-01

A major challenge in biology is identifying distinct cell classes and mapping their interactions in vivo. Tissue-dissociative technologies enable deep single cell molecular profiling but do not provide spatial information. We developed a proximity ligation in situ hybridization technology (PLISH) with exceptional signal strength, specificity, and sensitivity in tissue. Multiplexed data sets can be acquired using barcoded probes and rapid label-image-erase cycles, with automated calculation of single cell profiles, enabling clustering and anatomical re-mapping of cells. We apply PLISH to expression profile ~2900 cells in intact mouse lung, which identifies and localizes known cell types, including rare ones. Unsupervised classification of the cells indicates differential expression of ‘housekeeping’ genes between cell types, and re-mapping of two sub-classes of Club cells highlights their segregated spatial domains in terminal airways. By enabling single cell profiling of various RNA species in situ, PLISH can impact many areas of basic and medical research. PMID:29319504

On subclasses of opioid analgesics.

PubMed

Raffa, Robert B

2014-12-01

The history of discovery of analgesic drugs has followed a trajectory from original serendipitous discovery of plant-derived substances to laboratory creation of customized molecules that are intentionally designed to interact with specific receptors of neurotransmitters involved in either the transmission of the pain signal or the attenuation of such a signal. The drugs most recently developed have been designed to provide incremental greater separation between pain relief and adverse effects. The result has been drugs that have individualized pharmacodynamic and pharmacokinetic characteristics that represent specific advances in basic science and translate into unique clinical profiles. Several of the drugs include non-opioid components. They retain some of the features of opioids, but have distinct clinical characteristics that differentiate them from traditional opioids. Thus they defy simple classification as opioids. A summary is provided of the development of the modern view of multi-mechanistic pain and its treatment using analgesics that have multi-mechanisms of action (consisting of both opioid and non-opioid components). Descriptions of examples of such current analgesics and of those that have pharmacokinetic characteristics that result in atypical opioid clinical profiles are given. By serendipity or design, several current strong analgesics have opioid components of action, but have an additional non-opioid mechanism of action or some pharmacokinetic feature that gives them an atypical opioid clinical profile and renders them not easily classified as classical opioids. An appreciation that there are now opioid analgesics that differentiate from classical opioids in ways that defy their simplistic classification as opioids suggests that recognition of subclasses of opioid analgesics would be more accurate scientifically and would be more informative for healthcare providers and regulators. This would likely lead to positive outcomes for the clinical use and regulatory control of the current drugs, and provide direction/strategy for the discovery of new drugs.

Isotypes and antigenic profiles of pemphigus foliaceus and pemphigus vulgaris autoantibodies.

PubMed

Hacker, Mary K; Janson, Marleen; Fairley, Janet A; Lin, Mong-Shang

2002-10-01

In this study we systematically characterized isotype profiles and antigenic and tissue specificity of antidesmoglein autoantibodies from patients with pemphigus foliaceus (PF) and pemphigus vulgaris (PV) using enzyme-linked immunoabsorbent assays (ELISA), indirect immunofluorescence (IIF) staining, and immunoblotting (IB). In PF, we found that IgG1 antidesmoglein-1 (Dsg1) reacts with a linear epitope(s) on the ectodomain of Dsg1, while its IgG4 counterpart recognizes a conformational epitope(s). These two subclasses of anti-Dsg1 are both capable of recognizing tissues from monkey esophagus and adult human skin, but IgG1 is not able to react with mouse skin, which may explain why this isotype of anti-Dsg1 failed to induce PF-like lesions in the passive transfer animal model. In mucosal PV patients, we found that both IgG1 and IgG4 only recognized monkey esophagus tissue by IIF, except in one patient, indicating that these antibodies react with a unique conformational epitope(s) that is present in mucosal but not skin tissue. In generalized PV, IgG1 anti-Dsg3 autoantibodies appeared to recognize a linear epitope(s) on the Dsg3 ectodomain. In contrast, IgG4 anti-Dsg3 antibodies recognized both linear and conformational epitopes on the Dsg3 molecule. Interestingly, the IgG1 anti-Dsg3 antibodies failed to react with human and mouse skin tissues, suggesting that this subclass of autoantibodies may not play an essential role in the development of PV suprabasilar lesions. In summary, we conclude that this study further elucidates the pathological mechanisms of PF and PV autoantibodies by revealing their distinct isotype and antigenic profiles. This information may help us to better understand the autoimmune mechanisms underlying the development of pemphigus.

Transcriptional Networks in Single Perivascular Cells Sorted from Human Adipose Tissue Reveal a Hierarchy of Mesenchymal Stem Cells.

PubMed

Hardy, W Reef; Moldovan, Nicanor I; Moldovan, Leni; Livak, Kenneth J; Datta, Krishna; Goswami, Chirayu; Corselli, Mirko; Traktuev, Dmitry O; Murray, Iain R; Péault, Bruno; March, Keith

2017-05-01

Adipose tissue is a rich source of multipotent mesenchymal stem-like cells, located in the perivascular niche. Based on their surface markers, these have been assigned to two main categories: CD31 - /CD45 - /CD34 + /CD146 - cells (adventitial stromal/stem cells [ASCs]) and CD31 - /CD45 - /CD34 - /CD146 + cells (pericytes [PCs]). These populations display heterogeneity of unknown significance. We hypothesized that aldehyde dehydrogenase (ALDH) activity, a functional marker of primitivity, could help to better define ASC and PC subclasses. To this end, the stromal vascular fraction from a human lipoaspirate was simultaneously stained with fluorescent antibodies to CD31, CD45, CD34, and CD146 antigens and the ALDH substrate Aldefluor, then sorted by fluorescence-activated cell sorting. Individual ASCs (n = 67) and PCs (n = 73) selected from the extremities of the ALDH-staining spectrum were transcriptionally profiled by Fluidigm single-cell quantitative polymerase chain reaction for a predefined set (n = 429) of marker genes. To these single-cell data, we applied differential expression and principal component and clustering analysis, as well as an original gene coexpression network reconstruction algorithm. Despite the stochasticity at the single-cell level, covariation of gene expression analysis yielded multiple network connectivity parameters suggesting that these perivascular progenitor cell subclasses possess the following order of maturity: (a) ALDH br ASC (most primitive); (b) ALDH dim ASC; (c) ALDH br PC; (d) ALDH dim PC (least primitive). This order was independently supported by specific combinations of class-specific expressed genes and further confirmed by the analysis of associated signaling pathways. In conclusion, single-cell transcriptional analysis of four populations isolated from fat by surface markers and enzyme activity suggests a developmental hierarchy among perivascular mesenchymal stem cells supported by markers and coexpression networks. Stem Cells 2017;35:1273-1289. © 2017 AlphaMed Press.

Effect of transmission intensity and age on subclass antibody responses to Plasmodium falciparum pre-erythrocytic and blood-stage antigens.

PubMed

Noland, Gregory S; Jansen, Paul; Vulule, John M; Park, Gregory S; Ondigo, Bartholomew N; Kazura, James W; Moormann, Ann M; John, Chandy C

2015-02-01

Cytophilic immunoglobulin (IgG) subclass responses (IgG1 and IgG3) to Plasmodium falciparum antigens have been associated with protection from malaria, yet the relative importance of transmission intensity and age in generation of subclass responses to pre-erythrocytic and blood-stage antigens have not been clearly defined. We analyzed IgG subclass responses to the pre-erythrocytic antigens CSP, LSA-1, and TRAP and the blood-stage antigens AMA-1, EBA-175, and MSP-1 in asymptomatic residents age 2 years or older in stable (n=116) and unstable (n=96) transmission areas in Western Kenya. In the area of stable malaria transmission, a high prevalence of cytophilic (IgG1 and IgG3) antibodies to each antigen was seen in all age groups. Prevalence and levels of cytophilic antibodies to pre-erythrocytic and blood-stage P. falciparum antigens increased with age in the unstable transmission area, yet IgG1 and IgG3 responses to most antigens for all ages in the unstable transmission area were less prevalent and lower in magnitude than even the youngest age group from the stable transmission area. The dominance of cytophilic responses over non-cytophilic (IgG2 and IgG4) was more pronounced in the stable transmission area, and the ratio of IgG3 over IgG1 generally increased with age. In the unstable transmission area, the ratio of cytophilic to non-cytophilic antibodies did not increase with age, and tended to be IgG3-biased for pre-erythrocytic antigens yet IgG1-biased for blood-stage antigens. The differences between areas could not be attributed to active parasitemia status, as there were minimal differences in antibody responses between those positive and negative for Plasmodium infection by microscopy in the stable transmission area. Individuals in areas of unstable transmission have low cytophilic to non-cytophilic IgG subclass ratios and low IgG3:IgG1 ratios to P. falciparum antigens. These imbalances could contribute to the persistent risk of clinical malaria in these areas and serve as population-level, age-specific biomarkers of transmission. Copyright © 2014 Elsevier B.V. All rights reserved.

Genetic risk scores associated with baseline lipoprotein subfraction concentrations do not associate with their responses to fenofibrate

USDA-ARS?s Scientific Manuscript database

Lipoprotein subclass concentrations are modifiable markers of cardiovascular disease risk. Fenofibrate is known to show beneficial effects on lipoprotein subclasses, but little is known about the role of genetics in mediating the responses of lipoprotein subclasses to fenofibrate. A recent genomewid...

Alterations in IgG subclasses in acquired immune deficiency syndrome.

PubMed

Outschoorn, I M; Lluberes, R; Natta, C L

1989-01-01

Decreased IgG subclass levels in pyogenic infections and immunocompromised situations have been described. A study was made to determine IgG subclass levels in four groups of 68 Hispanic patients. The first group consisted of 25 terminal patients with AIDS, the second group of 20 i.v. drug abusers, and the third group of eight hospital patients with neither a diagnosis of AIDS/ARC nor a history of i.v. drug abuse. IgG subclass levels of these 53 cases were compared with those of a fourth group of 15 normal controls. The total IgG, IgA, and IgM levels as well as the four IgG subclass concentrations were measured by radial immunodiffusion using appropriate standards and specific antisera. The first two groups had similar values, with an average IgG level of 10.37 g/liter; IgA, 2.68; and IgM, 1.78; subclass levels were IgG1, 6.68 g/liter; IgG2, 2.77; IgG3, 0.34; and IgG4, 0.68. These were significantly lower than those of controls, except for IgG4. Determination of minor subclasses may offer some possibilities for immunomodulation and therapy and could be useful in terms of prognosis.

Comprehensive Profiling of Ethylene Response Factor Expression Identifies Ripening-Associated ERF Genes and Their Link to Key Regulators of Fruit Ripening in Tomato1[OPEN

PubMed Central

Gomes, Bruna Lima; Mila, Isabelle; Frasse, Pierre; Zouine, Mohamed; Bouzayen, Mondher

2016-01-01

Our knowledge of the factors mediating ethylene-dependent ripening of climacteric fruit remains limited. The transcription of ethylene-regulated genes is mediated by ethylene response factors (ERFs), but mutants providing information on the specific role of the ERFs in fruit ripening are still lacking, likely due to functional redundancy among this large multigene family of transcription factors. We present here a comprehensive expression profiling of tomato (Solanum lycopersicum) ERFs in wild-type and tomato ripening-impaired tomato mutants (Never-ripe [Nr], ripening-inhibitor [rin], and non-ripening [nor]), indicating that out of the 77 ERFs present in the tomato genome, 27 show enhanced expression at the onset of ripening while 28 display a ripening-associated decrease in expression, suggesting that different ERFs may have contrasting roles in fruit ripening. Among the 19 ERFs exhibiting the most consistent up-regulation during ripening, the expression of 11 ERFs is strongly down-regulated in rin, nor, and Nr tomato ripening mutants, while only three are consistently up-regulated. Members of subclass E, SlERF.E1, SlERF.E2, and SlERF.E4, show dramatic down-regulation in the ripening mutants, suggesting that their expression might be instrumental in fruit ripening. This study illustrates the high complexity of the regulatory network connecting RIN and ERFs and identifies subclass E members as the most active ERFs in ethylene- and RIN/NOR-dependent ripening. PMID:26739234

[Antiviral activity of IgG subclasses of immunoglobulin preparations for intravenous use].

PubMed

Litwińska, B; Bucholc, B; Biesiadecka, A; Kańtoch, M

1993-01-01

Preparations of human immunoglobulins for intravenous use (IVIG) should contain proper percentage of IgG subclasses, responding to physiological preparations with preserved activity of antibodies. The study was aimed at establishment of activity against measles, CMV and HSV viruses in individual subclasses of Bioglobulin (Biomed, Warszawa) and a comparison with preparation Polygam (Baxter, USA). Indirect immunofluorescence test was used. The results revealed presence of antiviral activity mostly in subclass IgG1 and also in IgG3, which is in keeping with results obtained by other authors. We have found an anti-HSV activity in a subclass IgG2 and IgG4 in IVIG preparations which was not yet described in the literature; it is confirmed, however, in investigations with application of sera of HSV-positive persons. These discrepancies may be caused by different methods of detection. Viral antigens in ELISA and IF tests may differ among themselves by content of individual epitopes. Basing on obtained results it can be stated that Polish preparation Bioglobulin (in which for the first time antiviral activity was determined in subclasses) is comparable with Polygam.

Autoantibody heritability in thyroiditis: IgG subclass contributions.

PubMed

Outschoorn, Ingrid M; Talor, Monica V; Hoffman, William H; Rowley, Merrill J; Mackay, Ian R; Rose, Noel R; Burek, C Lynne

2011-05-01

Using a simple screening technique called regression of offspring on mid-parent (ROMP) to examine the role of IgG subclasses in affected and unaffected siblings of children and adolescents with autoimmune thyroid disease and their parents, both total-restricted and subclass-restricted autoantibodies to thyroglobulin (Tg) were assayed quantitatively for each of the IgG subclasses. There was a significant correlation of anti-Tg titer of probands with parental titers in thyrotoxicosis (TT), (R(2) = 0.569, p = 0.001), but not in chronic lymphocytic thyroiditis. The most striking correlation was in TT patients of African-American ancestry, (R(2) = 0.9863, p = 0.0007). Additional insight is provided by examining the contributions of the IgG subclasses individually, particularly those whose concentrations appear not to have direct influence on the total IgG titers. Thus, using small numbers of patients, and assaying the IgG subclass distributions, as well as any other immunoglobulin isotypes that are significantly altered in autoantibody assays, ROMP can be performed rapidly to ascertain which quantifiable parameters may be usefully extended to predict disease onset and progression.

Quantitative analysis of immunoglobulin subclasses and subclass specific glycosylation by LC-MS-MRM in liver disease.

PubMed

Yuan, Wei; Sanda, Miloslav; Wu, Jing; Koomen, John; Goldman, Radoslav

2015-02-26

Aberrant glycosylation of IgGs has been linked to human diseases, including liver disease. In this study, we have quantified plasma immunoglobulins in cirrhosis (CIR) and hepatocellular carcinoma (HCC) and employed a novel LC-MS-MRM assay to quantify glycoforms of IgG subclasses 1-4. Glycan oxonium ions and peptide-GlcNAc fragment ions were utilized to quantify the IgG glycoforms purified by affinity chromatography with normalization to the unique peptide for each IgG subclass. Our results indicate that HCC patients have increased circulating IgG1, IgG3, IgA1, and IgM compared to healthy controls; comparison of HCC and CIR patients shows that HCC patients have significantly higher concentration of IgG1 and IgM but lower concentration of IgG2. An increase in galactose-deficient core fucosylated glycoforms was consistently observed in CIR and HCC patients. The FA2G0 and FA2BG0 glycoforms increase approximately 2-fold in all IgG subclasses accompanied by a decrease in the FA2G2 glycoform. Fucosylation changes are less pronounced but we have detected increased degree of fucosylation in the IgG1 and IgG3 glycoforms. In conclusion, we have optimized a sensitive and selective LC-MS-MRM method for the quantification of immunoglobulin subclasses and their site specific glycoforms, demonstrating that both quantities and glycoforms of immunoglobulins change significantly in liver disease progression to HCC. We have demonstrated that both quantities and glycoforms of immunoglobulin subclasses change significantly in liver disease progression to HCC through quantitative study of immunoglobulin subclasses and their site specific glycoforms using a sensitive and selective LC-MS-MRM method. Redistribution of the glycoforms of specific immunoglobulin subclasses could have important implications for receptor mediated responses affecting the progression of liver disease. Copyright © 2015 Elsevier B.V. All rights reserved.

Change-in-ratio methods for estimating population size

USGS Publications Warehouse

Udevitz, Mark S.; Pollock, Kenneth H.; McCullough, Dale R.; Barrett, Reginald H.

2002-01-01

Change-in-ratio (CIR) methods can provide an effective, low cost approach for estimating the size of wildlife populations. They rely on being able to observe changes in proportions of population subclasses that result from the removal of a known number of individuals from the population. These methods were first introduced in the 1940’s to estimate the size of populations with 2 subclasses under the assumption of equal subclass encounter probabilities. Over the next 40 years, closed population CIR models were developed to consider additional subclasses and use additional sampling periods. Models with assumptions about how encounter probabilities vary over time, rather than between subclasses, also received some attention. Recently, all of these CIR models have been shown to be special cases of a more general model. Under the general model, information from additional samples can be used to test assumptions about the encounter probabilities and to provide estimates of subclass sizes under relaxations of these assumptions. These developments have greatly extended the applicability of the methods. CIR methods are attractive because they do not require the marking of individuals, and subclass proportions often can be estimated with relatively simple sampling procedures. However, CIR methods require a carefully monitored removal of individuals from the population, and the estimates will be of poor quality unless the removals induce substantial changes in subclass proportions. In this paper, we review the state of the art for closed population estimation with CIR methods. Our emphasis is on the assumptions of CIR methods and on identifying situations where these methods are likely to be effective. We also identify some important areas for future CIR research.

Distribution of immunoglobulin G (IgG) and A (IgA) subclasses following Q fever vaccination with soluble phase I Coxiella burnetii extract.

PubMed

Camacho, M T; Outschoorn, I; Kovácová, E; Téllez, A

2000-03-06

High levels of IgG1, IgG3 and IgA2 antibodies have been observed in patients with Q fever following Coxiella burnetii infection. This IgG subclass distribution is more typical of viral and autoimmune diseases than of bacterial infections. It seemed, therefore, of interest to carry out a prospective study of the distribution of immunoglobulin subclasses after vaccination with phase I C. burnetii tricloroacetic soluble extracts to detect possible differences with respect to natural infection. The antibody response found in vaccinees was mainly restricted to the IgG1, IgG2 and IgA1 subclasses. These findings confirm differences in isotype distribution when compared to those of patients with acute or chronic Coxiella infections and opens an area of interest with respect to the role of IgA subclasses.

Department of Defense: Electronic Biometric Transmission Specification. Version 2.0

DTIC Science & Technology

2009-03-27

Abstractions = ABSTRACT Insignias & Symbols = SYMBOL Other Images = OTHER Information Item Number: 3 Tattoo Subclass Description: This information item...Tattoo Subclasses: American Flag = USA State Flag = STATE Nazi Flag = NAZI Confederate Flag = CONFED British Flag = BRIT Miscellaneous Flags = MFLAG...Vegetables = MPLANT Flag Tattoo Subclasses: American Flag = USA State Flag = STATE Nazi Flag = NAZI Confederate Flag = CONFED British Flag = BRIT

Notation for human immunogobulin subclasses.

PubMed

Kunkel, H G; Fahey, J L; Franklin, E C; Osserman, E F; Terry, W D

1966-01-01

After consultation between immunologists from a number of countries a nomenclature for human immunoglobulins was proposed in 1964 and was published in the Bulletin of the World Health Organization.(1) However, that proposed scheme of notation, which has already gained wide acceptance, left several specialized areas of nomenclature still to be resolved; one of these was the subclasses of immunoglobulins. Some of the research workers most closely concerned with the problem have now agreed upon a unified scheme for the notation of the human immunoglobulin subclasses, and, in particular, of the immunoglobulin G subclass, for which two different nomenclatorial schemes have been followed in recent years. Their proposals are given below.

Serum lipoproteins are not associated with the severity of asthma.

PubMed

Scaduto, Federica; Giglio, Rosaria Vincenza; Benfante, Alida; Nikolic, Dragana; Montalto, Giuseppe; Rizzo, Manfredi; Scichilone, Nicola

2018-06-01

Asthma is a chronic inflammatory disorder of the bronchi with a complicated and largely unknown pathogenesis. In this context, an emerging role is attributed to the apolipoproteins which serve as structural components of plasma lipoproteins. Low density lipoproteins (LDL) may be involved in the inflammatory pathways of the asthmatic airways; in particular, small dense LDL (sdLDL) particles were associated with increased oxidative susceptibility compared to medium and large sized LDL. In our previous study, we found a positive correlation between forced expiratory volume 1 s (FEV 1 ) % predicted and larger LDL particles (LDL-1), and an inverse correlation between FEV 1 % predicted and sdLDL (LDL-3) in mild, untreated asthmatics. Although LDL appear to be important modulators of inflammation, data on their clinical implications are still lacking. The aim of the study is to investigate whether LDL subclasses correlate with the severity of asthma, assuming that the atherogenic and most pro-inflammatory LDL contribute to ignite and perpetuate the airway inflammatory processes. The study was conducted in one visit, and included clinical and lung functional assessments, as well as measurements of serum concentrations of the LDL subclasses. Non-denaturing, linear polyacrylamide gel electrophoresis was used to separate and measure LDL subclasses, with the LipoPrint © System (Quantimetrix Corporation, Redondo Beach, CA, USA). LDL subclasses were distributed as seven bands (LDL-1 to LDL-7), LDL-1 and -2 being defined as large LDL (least pro-inflammatory), and LDL-3 to 7 defined as sdLDL (most pro-inflammatory). 70 asthmatics under inhaled treatment (M/F: 35/35) were enrolled; 10 healthy subjects (M/F: 3/7) served as controls. In the asthmatic group, FEV 1 % predicted was 81 ± 22% (mean ± SD), vital capacity (VC) % predicted was 97 ± 18%, and FEV 1 /FVC was 0.68 ± 0.1. The mean asthma control test (ACT) score was 18 ± 5. LDL-1 were significantly lower in asthmatics as compared to controls (18 ± 4% vs. 22 ± 4%, p = 0.008). On the contrary, LDL-2 (12 ± 4% vs. 12 ± 5%) and LDL-3 (3 ± 3% vs. 2 ± 2%) were not statistically different between the two groups; smaller subclasses were undetectable. To comply with the design of the study, subjects were classified according to their degree of severity into the 5 Global Initiative for Asthma (GINA) steps: Step 1 (M/F: 4/3, 44 ± 12 yrs), Step 2 (M/F: 1/2, 37 ± 11 yrs), Step 3 (M/F: 12/7, 47 ± 12 yrs), Step 4 (M/F: 8/15, 54 ± 12 yrs), and Step 5 (M/F: 7/9, 56 ± 9 yrs). None of the LDL subclasses showed significant differences between classes of severity: LDL-1 were 16.1 ± 5.6% in Step 1, 18 ± 2.8% in Step 2, 16.7 ± 3.7% in Step 3, 18 ± 3.3% in Step 4, and 19.5 ± 3.2% in Step 5 (p = NS); LDL2 were 14 ± 3.6%, 15 ± 3.4%, 12.4 ± 5.3%, 12.7 ± 4.4% and 11.3 ± 4.2%, respectively (p = NS); LDL3 were 5 ± 5.2%, 4.4 ± 2.6%, 3.3 ± 3.6%, 3.2 ± 2.6% and 2.4 ± 1.8%, p = NS. Finally, no relationship was detected between LDL subclasses and lung function parameters as well as the ACT scores. The current findings confirm a role of LDL as a potential biomarker in the diagnostic process for asthma, and suggest that LDL cannot be used as marker of severity of the disease. Copyright © 2018. Published by Elsevier Ltd.

The effect of exercise on plasma lipids and LDL subclass metabolism in miniature swine.

PubMed

Stucchi, A F; Terpstra, A H; Foxall, T L; Nicolosi, R J; Smith, S C

1991-05-01

The effects of exercise on plasma lipids and lipoproteins, high density lipoprotein (HDL) subclass cholesterol levels, and low density lipoprotein (LDL) subclass composition and metabolism were studied in Yucatan miniature swine following 2 yr of training. The exercise protocol produced significant training effects. Post-heparin lipolytic activity was also significantly increased. Although plasma cholesterol and triglycerides did not differ significantly (P = 0.08) between the exercised and control groups, multivariate analysis indicated a strong association between lipoprotein lipase (LPL) and HDL2-C (P less than 0.0001). Although HDL-C levels rose only slightly (P less than 0.09) with exercise, a significant shift was noted in the distribution of cholesterol from the HDL3 to the HDL2 fractions, perhaps mediated by the substantial increase in LPL activity. Exercise had little effect on the chemical composition of the major lipoprotein classes; however, the triglyceride content of the lighter LDL1 subclass was significantly reduced. In the more dense LDL2 subclass, exercise resulted in a significant decrease in triglycerides concomitant with a significant increase in free cholesterol levels. In contrast with the small reductions in fractional catabolic rates (FCR) in either subclass, production rates of the exercised group were reduced, which accounted for the reduction in LDL subclass pool size. These data indicate that exercise produces subtle but significant changes in lipoprotein metabolism that have been previously associated with reduced risk of atherosclerosis.

Indices of anti-dengue immunoglobulin G subclasses in adult Mexican patients with febrile and hemorrhagic dengue in the acute phase.

PubMed

Posadas-Mondragón, Araceli; Aguilar-Faisal, José Leopoldo; Chávez-Negrete, Adolfo; Guillén-Salomón, Edith; Alcántara-Farfán, Verónica; Luna-Rojas, Lucero; Ávila-Trejo, Amanda Marineth; Del Carmen Pacheco-Yépez, Judith

2017-10-01

Heterologous secondary infections are at increased risk of developing dengue hemorrhagic fever (DHF) because of antibody-dependent enhancement (ADE). IgG subclasses can fix and activate complement and bind to Fcɣ receptors. These factors may also play an important role in the development of ADE and thus in the pathogenesis of DHF. The aim of this study was to analyze the indices of anti-dengue IgG subclasses in adult patients with febrile and hemorrhagic dengue in the acute phase. In 2013, 129 patients with dengue fever (DF) and 57 with DHF in Veracruz, Mexico were recruited for this study and anti-dengue IgM and IgG determined by capture ELISA. Anti-dengue IgG subclasses were detected by indirect ELISA. Anti-dengue IgG2 and IgG3 subclasses were detected in patients with dengue. IgG1 increased significantly in the sera of patients with both primary and secondary infections and DHF, but was higher in patients with secondary infections. The IgG4 subclass index was significantly higher in the sera of patients with DHF than in that of those with DF, who were in the early and late acute phase of both primary and secondary infection. In conclusion, indices of subclasses IgG1 and IgG4 were higher in patients with DHF. © 2017 The Societies and John Wiley & Sons Australia, Ltd.

Area-specific development of distinct projection neuron subclasses is regulated by postnatal epigenetic modifications

PubMed Central

Harb, Kawssar; Magrinelli, Elia; Nicolas, Céline S; Lukianets, Nikita; Frangeul, Laura; Pietri, Mariel; Sun, Tao; Sandoz, Guillaume; Grammont, Franck; Jabaudon, Denis; Studer, Michèle; Alfano, Christian

2016-01-01

During cortical development, the identity of major classes of long-distance projection neurons is established by the expression of molecular determinants, which become gradually restricted and mutually exclusive. However, the mechanisms by which projection neurons acquire their final properties during postnatal stages are still poorly understood. In this study, we show that the number of neurons co-expressing Ctip2 and Satb2, respectively involved in the early specification of subcerebral and callosal projection neurons, progressively increases after birth in the somatosensory cortex. Ctip2/Satb2 postnatal co-localization defines two distinct neuronal subclasses projecting either to the contralateral cortex or to the brainstem suggesting that Ctip2/Satb2 co-expression may refine their properties rather than determine their identity. Gain- and loss-of-function approaches reveal that the transcriptional adaptor Lmo4 drives this maturation program through modulation of epigenetic mechanisms in a time- and area-specific manner, thereby indicating that a previously unknown genetic program postnatally promotes the acquisition of final subtype-specific features. DOI: http://dx.doi.org/10.7554/eLife.09531.001 PMID:26814051

Neutron stars: Observational diversity and evolution

NASA Astrophysics Data System (ADS)

Safi-Harb, S.

2017-12-01

Ever since the discovery of the Crab and Vela pulsars in their respective Supernova Remnants, our understanding of how neutron stars manifest themselves observationally has been dramatically shaped by the surge of discoveries and dedicated studies across the electromagnetic spectrum, particularly in the high-energy band. The growing diversity of neutron stars includes the highly magnetized neutron stars (magnetars) and the Central Compact Objects shining in X-rays and mostly lacking pulsar wind nebulae. These two subclasses of high-energy objects, however, seem to be characterized by anomalously high or anomalously low surface magnetic fields (thus dubbed as ‘magnetars’ and ‘anti-magnetars’, respectively), and have pulsar characteristic ages that are often much offset from their associated SNRs’ ages. In addition, some neutron stars act ‘schizophrenic’ in that they occasionally display properties that seem common to more than one of the defined subclasses. I review the growing diversity of neutron stars from an observational perspective, then highlight recent and on-going theoretical and observational work attempting to address this diversity, particularly in light of their magnetic field evolution, energy loss mechanisms, and supernova progenitors’ studies.

The Infection of Cucumber (Cucumis sativus L.) Roots by Meloidogyne incognita Alters the Expression of Actin-Depolymerizing Factor (ADF) Genes, Particularly in Association with Giant Cell Formation

PubMed Central

Liu, Bin; Liu, Xingwang; Liu, Ying; Xue, Shudan; Cai, Yanling; Yang, Sen; Dong, Mingming; Zhang, Yaqi; Liu, Huiling; Zhao, Binyu; Qi, Changhong; Zhu, Ning; Ren, Huazhong

2016-01-01

Cucumber (Cucumis sativus L.) is threatened by substantial yield losses due to the south root-knot nematode (Meloidogyne incognita). However, understanding of the molecular mechanisms underlying the process of nematode infection is still limited. In this study, we found that M. incognita infection affected the structure of cells in cucumber roots and treatment of the cytoskeleton inhibitor (cytochalasin D) reduced root-knot nematode (RKN) parasitism. It is known that Actin-Depolymerizing Factor (ADF) affects cell structure, as well as the organization of the cytoskeleton. To address the hypothesis that nematode-induced abnormal cell structures and cytoskeletal rearrangements might be mediated by the ADF genes, we identified and characterized eight cucumber ADF (CsADF) genes. Phylogenetic analysis showed that the cucumber ADF gene family is grouped into four ancient subclasses. Expression analysis revealed that CsADF1, CsADF2-1, CsADF2-2, CsADF2-3 (Subclass I), and CsADF6 (Subclass III) have higher transcript levels than CsADF7-1, CsADF7-2 (Subclass II genes), and CsADF5 (Subclass IV) in roots. Members of subclass I genes (CsADF1, CsADF2-1, CsADF2-2, and CsADF2-3), with the exception of CsADF2-1, exhibited a induction of expression in roots 14 days after their inoculation (DAI) with nematodes. However, the expression of subclass II genes (CsADF7-1 and CsADF7-2) showed no significant change after inoculation. The transcript levels of CsADF6 (Subclass III) showed a specific induction at 21 DAI, while CsADF5 (Subclass IV) was weakly expressed in roots, but was strongly up-regulated as early as 7 DAI. In addition, treatment of roots with cytochalasin D caused an approximately 2-fold down-regulation of the CsADF genes in the treated plants. These results suggest that CsADF gene mediated actin dynamics are associated with structural changes in roots as a consequence of M. incognita infection. PMID:27695469

Ruminant-produced trans-fatty acids raise plasma HDL particle concentrations in intact and ovariectomized female Hartley guinea pigs.

PubMed

Rice, Beth H; Kraft, Jana; Destaillats, Frédéric; Bauman, Dale E; Lock, Adam L

2012-09-01

Cardiovascular disease (CVD) is the leading cause of death among women worldwide, and risk for developing CVD increases postmenopause. Consumption of trans-fatty acids (tFA) has been positively associated with CVD incidence and mortality. The current study was designed to assess the effects of diets high in industrially produced (IP)-tFA, from partially hydrogenated vegetable oils (PHVO), and ruminant-produced (RP)-tFA, from butter oil (BO), on risk factors for CVD. Thirty-two female Hartley guinea pigs, one-half of which were ovariectomized (OVX) to mimic the postmenopausal condition, were fed hypercholesterolemic diets containing 9% by weight PHVO or BO (n = 8/diet and ovariectomy) for 8 wk. The plasma and hepatic lipids did not differ between IP- and RP-tFA groups or between intact and OVX guinea pigs. The BO diet resulted in higher concentrations of plasma total and small HDL particle subclass concentrations than the PHVO diet regardless of ovariectomy status. The intact BO group had higher concentrations of large HDL particles than the intact PHVO group. HDL mean particle size tended to be larger (P = 0.07) in the PHVO groups compared with the BO groups regardless of ovariectomy status. There was a trend toward an interaction between diet and ovariectomy status for LDL mean particle size, which tended to be larger in OVX guinea pigs fed PHVO (P = 0.07). In summary, consumption of IP- and RP-tFA resulted in differential effects on HDL particle subclass profiles in female guinea pigs. The effect of tFA consumption and hormonal status on HDL particle subclass metabolism and the subsequent impact on CVD in females warrants further investigation.

Genome-Wide Identification of TCP Family Transcription Factors in Medicago truncatula Reveals Significant Roles of miR319-Targeted TCPs in Nodule Development

PubMed Central

Wang, Hongfeng; Wang, Hongwei; Liu, Rong; Xu, Yiteng; Lu, Zhichao; Zhou, Chuanen

2018-01-01

TCP proteins, the plant-specific transcription factors, are involved in the regulation of multiple aspects of plant development among different species, such as leaf development, branching, and flower symmetry. However, thus far, the roles of TCPs in legume, especially in nodulation are still not clear. In this study, a genome-wide analysis of TCP genes was carried out to discover their evolution and function in Medicago truncatula. In total, 21 MtTCPs were identified and classified into class I and class II, and the class II MtTCPs were further divided into two subclasses, CIN and CYC/TB1. The expression profiles of MtTCPs are dramatically different. The universal expression of class I MtTCPs was detected in all organs. However, the MtTCPs in CIN subclass were highly expressed in leaf and most of the members in CYC/TB1 subclass were highly expressed in flower. Such organ-specific expression patterns of MtTCPs suggest their different roles in plant development. In addition, most MtTCPs were down-regulated during the nodule development, except for the putative MtmiR319 targets, MtTCP3, MtTCP4, and MtTCP10A. Overexpression of MtmiR319A significantly reduced the expression level of MtTCP3/4/10A/10B and resulted in the decreased nodule number, indicating the important roles of MtmiR319-targeted MtTCPs in nodulation. Taken together, this study systematically analyzes the MtTCP gene family at a genome-wide level and their possible functions in nodulation, which lay the basis for further explorations of MtmiR319/MtTCPs module in association with nodule development in M. truncatula.

Induction of a Th-1-biased IgG subclass response against equine herpesvirus type 1 in horses previously infected with type 4 virus.

PubMed

Bannai, Hiroshi; Tsujimura, Koji; Kondo, Takashi; Nemoto, Manabu; Yamanaka, Takashi; Sugiura, Takeo; Maeda, Ken; Matsumura, Tomio

2011-04-01

An immunoglobulin G (IgG) subclass response against equine herpesvirus type 1 (EHV-1) infection was investigated in horses that were naïve to EHV-1/4 and those that had previously been exposed to EHV-4. The IgG subclass response was determined by an ELISA using EHV-1-specific recombinant gG protein as an antigen. In most horses naïve to EHV-1/4, IgGa, IgGb, and IgG(T) were induced after experimental infection with EHV-1. In contrast, a subclass response dominated by IgGa and IgGb, with no apparent increase in IgG(T), was observed after EHV-1 infection in horses previously infected with EHV-4. Horses naturally infected with EHV-1 in the field showed similar responses. These results indicated that pre-infection with EHV-4 induced a Th-1-biased IgG subclass response against subsequent EHV-1 infection.

Carotenoid metabolic profiling and transcriptome-genome mining reveal functional equivalence among blue-pigmented copepods and appendicularia.

PubMed

Mojib, Nazia; Amad, Maan; Thimma, Manjula; Aldanondo, Naroa; Kumaran, Mande; Irigoien, Xabier

2014-06-01

The tropical oligotrophic oceanic areas are characterized by high water transparency and annual solar radiation. Under these conditions, a large number of phylogenetically diverse mesozooplankton species living in the surface waters (neuston) are found to be blue pigmented. In the present study, we focused on understanding the metabolic and genetic basis of the observed blue phenotype functional equivalence between the blue-pigmented organisms from the phylum Arthropoda, subclass Copepoda (Acartia fossae) and the phylum Chordata, class Appendicularia (Oikopleura dioica) in the Red Sea. Previous studies have shown that carotenoid-protein complexes are responsible for blue coloration in crustaceans. Therefore, we performed carotenoid metabolic profiling using both targeted and nontargeted (high-resolution mass spectrometry) approaches in four different blue-pigmented genera of copepods and one blue-pigmented species of appendicularia. Astaxanthin was found to be the principal carotenoid in all the species. The pathway analysis showed that all the species can synthesize astaxanthin from β-carotene, ingested from dietary sources, via 3-hydroxyechinenone, canthaxanthin, zeaxanthin, adonirubin or adonixanthin. Further, using de novo assembled transcriptome of blue A. fossae (subclass Copepoda), we identified highly expressed homologous β-carotene hydroxylase enzymes and putative carotenoid-binding proteins responsible for astaxanthin formation and the blue phenotype. In blue O. dioica (class Appendicularia), corresponding putative genes were identified from the reference genome. Collectively, our data provide molecular evidences for the bioconversion and accumulation of blue astaxanthin-protein complexes underpinning the observed ecological functional equivalence and adaptive convergence among neustonic mesozooplankton. © 2014 The Authors. Molecular Ecology Published by John Wiley & Sons Ltd.

Linkage-specific sialic acid derivatization for MALDI-TOF-MS profiling of IgG glycopeptides.

PubMed

de Haan, Noortje; Reiding, Karli R; Haberger, Markus; Reusch, Dietmar; Falck, David; Wuhrer, Manfred

2015-08-18

Glycosylation is a common co- and post-translational protein modification, having a large influence on protein properties like conformation and solubility. Furthermore, glycosylation is an important determinant of efficacy and clearance of biopharmaceuticals such as immunoglobulin G (IgG). Matrix-assisted laser desorption/ionization (MALDI)-time-of-flight (TOF)-mass spectrometry (MS) shows potential for the site-specific glycosylation analysis of IgG at the glycopeptide level. With this approach, however, important information about glycopeptide sialylation is not duly covered because of in-source and metastable decay of the sialylated species. Here, we present a highly repeatable sialic acid derivatization method to allow subclass-specific MALDI-TOF-MS analysis of tryptic IgG glycopeptides. The method, employing dimethylamidation with the carboxylic acid activator 1-ethyl-3-(3-dimethylamino)propyl)carbodiimide (EDC) and the catalyst 1-hydroxybenzotriazole (HOBt), results in different masses for the functionally divergent α2,3- and α2,6-linked sialic acids. Respective lactonization and dimethylamidation leads to their direct discrimination in MS and importantly, both glycan and peptide moieties reacted in a controlled manner. In addition, stabilization allowed the acquisition of fragmentation spectra informative with respect to glycosylation and peptide sequence. This was in contrast to fragmentation spectra of underivatized samples, which were dominated by sialic acid loss. The method allowed the facile discrimination and relative quantitation of IgG Fc sialylation in therapeutic IgG samples. The method has considerable potential for future site- and sialic acid linkage-specific glycosylation profiling of therapeutic antibodies, as well as for subclass-specific biomarker discovery in clinical IgG samples derived from plasma.

Role of immunoglobulin G subclasses in Q fever.

PubMed

Camacho, M T; Outschoorn, I; Tellez, A

1995-12-01

The progression of Q fever to either acute or chronic disease has been attributed both to biological characteristics of the bacteria and to the host immune response. In order to determine whether a specific immunoglobulin G (IgG) subclass distribution could play a diagnostic or prognostic role in Q fever, IgG subclass levels were measured in patients with acute or chronic disease. It was observed that (i) IgG1 and IgG3 levels were elevated in patients with chronic Q fever compared to patients with acute disease or normal controls; (ii) variations over time reflected inverse complementary relationships of subclass levels, such as between IgG1 and IgG3 compared with IgG2 and IgG4, or an inverse relationship between IgG1 and IgG2; (iii) variations in IgG2 and IgG3 total subclass levels during follow-up of patients with chronic Q fever showed a decrease in IgG2 with a concomitant increase in IgG3 two years from disease onset. These findings indicate that measurements of IgG subclasses may be a simple, additional tool useful in the diagnosis of Q fever. This data raises the question of an unusual immunoregulatory mechanism in Q fever that is implicated in the presentation of the clinical disease.

Efficacies of roadway safety improvements across functional subclasses of rural two-lane highways.

PubMed

Labi, Samuel

2011-08-01

Highway crash occurrence is a leading cause of unnatural deaths, and highway agencies continually seek to identify engineering measures to reduce crashes and to assess the efficacy of such measures. Most past studies on the effectiveness of roadway improvements in terms of crash reduction considered all rural two-lane sections as a single category of roads. However, it may be hypothesized that the differences in the mobility and accessibility characteristics that are reflected in (and due to) the different design standards between different functional subclasses in the rural two-lane highway system can lead to differences in efficacies of safety improvements at these subclasses. This paper investigates the efficacy of roadway improvements, in terms of crash reduction, at the various subclasses of rural two-lane highways. An empirical analysis of safety performance at each of the three subclasses of rural two-lane highways was carried out using the negative binomial modeling technique. For each subclass, crash prediction models were developed separately for the three levels of crash severity: property-damage only, injury, and fatal/injury. The crash factors that were considered include lane width, shoulder width, pavement surface friction, pavement condition, and horizontal and vertical alignments. After having developed the safety performance functions, the effectiveness (in terms of the extent of crash reduction, for different levels of crash severity) of highway safety enhancements at each highway subclass were determined using the theoretical concepts established in past literature. These enhancements include widening lanes, widening shoulders, enhancing pavement surface friction, and improving the vertical or horizontal alignment. The study found that there is empirical evidence to justify the decomposition of the family of rural two-lane roads into its constituent subclasses for purposes of analyzing the effectiveness of safety enhancement projects and thus to avoid underestimation or overestimation of benefits of safety improvements at this class of highways. Copyright © 2011 Elsevier Ltd. All rights reserved.

Quantitative Serum Nuclear Magnetic Resonance Metabolomics in Large-Scale Epidemiology: A Primer on -Omic Technologies

PubMed Central

Kangas, Antti J; Soininen, Pasi; Lawlor, Debbie A; Davey Smith, George; Ala-Korpela, Mika

2017-01-01

Abstract Detailed metabolic profiling in large-scale epidemiologic studies has uncovered novel biomarkers for cardiometabolic diseases and clarified the molecular associations of established risk factors. A quantitative metabolomics platform based on nuclear magnetic resonance spectroscopy has found widespread use, already profiling over 400,000 blood samples. Over 200 metabolic measures are quantified per sample; in addition to many biomarkers routinely used in epidemiology, the method simultaneously provides fine-grained lipoprotein subclass profiling and quantification of circulating fatty acids, amino acids, gluconeogenesis-related metabolites, and many other molecules from multiple metabolic pathways. Here we focus on applications of magnetic resonance metabolomics for quantifying circulating biomarkers in large-scale epidemiology. We highlight the molecular characterization of risk factors, use of Mendelian randomization, and the key issues of study design and analyses of metabolic profiling for epidemiology. We also detail how integration of metabolic profiling data with genetics can enhance drug development. We discuss why quantitative metabolic profiling is becoming widespread in epidemiology and biobanking. Although large-scale applications of metabolic profiling are still novel, it seems likely that comprehensive biomarker data will contribute to etiologic understanding of various diseases and abilities to predict disease risks, with the potential to translate into multiple clinical settings. PMID:29106475

Comprehensive analysis of mycolic acid subclass and molecular species composition of Mycobacterium bovis BCG Tokyo 172 cell wall skeleton (SMP-105).

PubMed

Uenishi, Yuko; Fujita, Yukiko; Kusunose, Naoto; Yano, Ikuya; Sunagawa, Makoto

2008-02-01

The mycobacterial cell envelope consists of a characteristic cell wall skeleton (CWS), a mycoloyl arabinogalactan peptidoglycan complex, and related hydrophobic components that contribute to the cell surface properties. Since mycolic acids have recently been reported to play crucial roles in host immune response, detailed molecular characterization of mycolic acid subclasses and sub-subclasses of CWS from Mycobacterium bovis BCG Tokyo 172 (SMP-105) was performed. Mycolic acids were liberated by alkali hydrolysis from SMP-105, and their methyl esters were separated by silica gel TLC into three subclasses: alpha-, methoxy-, and keto-mycolates. Each mycolate subclass was further separated by silver nitrate (AgNO(3))-coated silica gel TLC into sub-subclasses. Molecular weights of individual mycolic acid were determined by MALDI-TOF mass spectrometry. alpha-Mycolates were sub-grouped into cis, cis-dicyclopropanoic (alpha1), and cis-monocyclopropanoic-cis-monoenoic (alpha2) series; methoxy-mycolates were sub-grouped into cis-monocyclopropanoic (m1), trans-monocyclopropanoic (m2), trans-monoenoic (m3), cis-monocyclopropanoic-trans-monoenoic (m4), cis-monoenoic (m5), and cis-monocyclopropanoic-cis-monoenoic (m6) series; and keto-mycolates were sub-grouped into cis-monocyclopropanoic (k1), trans-monocyclopropanoic (k2), trans-monoenoic (k3), cis-monoenoic (k4), and cis-monocyclopropanoic-cis-monoenoic (k5) series. The position of each functional group, including cyclopropane rings and methoxy and keto groups, was determined by analysis of the meromycolates with fast atom bombardment (FAB) mass spectrometry and FAB mass-mass spectrometry, and the cis/trans ratio of cyclopropane rings and double bonds were determined by NMR analysis of methyl mycolates. Mycolic acid subclass and molecular species composition of SMP-105 showed characteristic features including newly-identified cis-monocyclopropanoic-trans-monoenoic mycolic acid (m4).

Use of OM-85 BV in children suffering from recurrent respiratory tract infections and subnormal IgG subclass levels.

PubMed

Del-Río-Navarro, B E; Luis Sienra-Monge, J J; Berber, A; Torres-Alcántara, S; Avila-Castañón, L; Gómez-Barreto, D

2003-01-01

Recurrent acute respiratory tract infections (RARTIs) in children are related to IgG subclass deficiencies. The aim of the trial was to evaluate the effect of OM-85 BV in the number of RARTIs as well as in the IgG subclass levels. This was a randomized, double-blind, placebo-controlled clinical trial. Patients of ages three to six years, having three or more documented ARTIs during the last six months with subnormal IgG subclass levels were included. Patients took either one capsule of OM-85 BV (3.5 mg) or placebo orally every day for ten consecutive days per month during three consecutive months. Patients were followed three further months without drug intake. IgG subclass levels were determined before and after treatment. IgG4 levels diminished after the OM-85 BV treatment (-3 [-8.0, -1.0] median difference [95 % CI] p < 0.05 by Wilcoxon test). No other significant changes in IgG subclasses were observed. After six months the patients in the OM-85 BV group (n = 20) experienced 2.8 1.4 (mean SD) ARTIs, while the patients in the placebo group (n = 20) suffered 5.2 1.5 ARTIs (-2.4 [3.3, -1.5] mean difference [95 % CI] p < 0.001 by Student's t test). Three patients with OM-85 BV had gastrointestinal events related to drug administration, as well as three placebo patients. This study demonstrated the clinical benefit of OM-85 BV in patients suffering from RARTIs and subnormal levels of IgG subclasses. This trial opens new perspectives in the research of the mechanism of action of OM-85 BV.

Dietary fatty acids were not independently associated with lipoprotein subclasses in elderly women.

PubMed

Alaghehband, Fatemeh Ramezan; Lankinen, Maria; Värri, Miika; Sirola, Joonas; Kröger, Heikki; Erkkilä, Arja T

2017-07-01

Dietary fatty acids are known to affect serum lipoproteins; however, little is known about the associations between consumption of dietary fatty acids and lipoprotein subclasses. In this study, we hypothesized that there is an association between dietary fatty acids and lipoprotein subclasses and investigated the cross-sectional association of dietary fat intake with subclasses of lipoproteins in elderly women. Altogether, 547 women (aged ≥65 years) who were part of OSTPRE cohort participated. Dietary intake was assessed by 3-day food records, lifestyle, and health information obtained through self-administrated questionnaires, and lipoprotein subclasses were determined by nuclear magnetic resonance spectroscopy. To analyze the associations between fatty acids and lipoprotein subclasses, we used Pearson and Spearman correlation coefficients and the analysis of covariance (ANCOVA) test with, adjustment for physical activity, body mass index, age, smoking status, and intake of lipid-lowering drugs. There were significant correlations between saturated fatty acids (SFA; % of energy) and concentrations of large, medium, and small low-density lipoproteins (LDL); total cholesterol in large, medium, and small LDL; and phospholipids in large, medium, and small LDL, after correction for multiple testing. After adjustment for covariates, the higher intake of SFA was associated with smaller size of LDL particles (P = .04, ANCOVA) and lower amount of triglycerides in small very low-density lipoproteins (P = .046, ANCOVA). However, these associations did not remain significant after correction for multiple testing. In conclusion, high intake of SFA may be associated with the size of LDL particles, but the results do not support significant, independent associations between dietary fatty acids and lipoprotein subclasses. Copyright © 2017 Elsevier Inc. All rights reserved.

An Eocene orthocone from Antarctica shows convergent evolution of internally shelled cephalopods

PubMed Central

Bengtson, Stefan; Reguero, Marcelo A.; Mörs, Thomas

2017-01-01

Background The Subclass Coleoidea (Class Cephalopoda) accommodates the diverse present-day internally shelled cephalopod mollusks (Spirula, Sepia and octopuses, squids, Vampyroteuthis) and also extinct internally shelled cephalopods. Recent Spirula represents a unique coleoid retaining shell structures, a narrow marginal siphuncle and globular protoconch that signify the ancestry of the subclass Coleoidea from the Paleozoic subclass Bactritoidea. This hypothesis has been recently supported by newly recorded diverse bactritoid-like coleoids from the Carboniferous of the USA, but prior to this study no fossil cephalopod indicative of an endochochleate branch with an origin independent from subclass Bactritoidea has been reported. Methodology/Principal findings Two orthoconic conchs were recovered from the Early Eocene of Seymour Island at the tip of the Antarctic Peninsula, Antarctica. They have loosely mineralized organic-rich chitin-compatible microlaminated shell walls and broadly expanded central siphuncles. The morphological, ultrustructural and chemical data were determined and characterized through comparisons with extant and extinct taxa using Scanning Electron Microscopy/Energy Dispersive Spectrometry (SEM/EDS). Conclusions/Significance Our study presents the first evidence for an evolutionary lineage of internally shelled cephalopods with independent origin from Bactritoidea/Coleoidea, indicating convergent evolution with the subclass Coleoidea. A new subclass Paracoleoidea Doguzhaeva n. subcl. is established for accommodation of orthoconic cephalopods with the internal shell associated with a broadly expanded central siphuncle. Antarcticerida Doguzhaeva n. ord., Antarcticeratidae Doguzhaeva n. fam., Antarcticeras nordenskjoeldi Doguzhaeva n. gen., n. sp. are described within the subclass Paracoleoidea. The analysis of organic-rich shell preservation of A. nordenskjoeldi by use of SEM/EDS techniques revealed fossilization of hyposeptal cameral soft tissues. This suggests that a depositional environment favoring soft-tissue preservation was the factor enabling conservation of the weakly mineralized shell of A. nordenskjoeldi. PMID:28248970

A family study of IgG subclasses in sickle cell anemia.

PubMed

Outschoorn, I M; Natta, C

1983-01-01

Three siblings with sickle cell anemia were studied immunologically and hematologically. Their patterns of Protein A-Sepharose chromatography distribution showed considerable heterogeneity, particularly with respect to the IgG2 and IgG3 subclasses, even though their hematological make up was similar. An attempt was made to correlate their IgG2: IgG1 subclass ratios with their clinical history of recurrent bacterial infections, as well as a possible compensatory IgG3 heterogeneity.

Serum IgG subclass levels and risk of exacerbations and hospitalizations in patients with COPD.

PubMed

Leitao Filho, Fernando Sergio; Ra, Seung Won; Mattman, Andre; Schellenberg, Robert S; Criner, Gerard J; Woodruff, Prescott G; Lazarus, Stephen C; Albert, Richard; Connett, John E; Han, Meilan K; Martinez, Fernando J; Leung, Janice M; Paul Man, S F; Aaron, Shawn D; Reed, Robert M; Sin, Don D

2018-02-14

The literature is scarce regarding the prevalence and clinical impact of IgG subclass deficiency in COPD. We investigated the prevalence of IgG subclass deficiencies and their association with exacerbations and hospitalizations using subjects from two COPD cohorts. We measured IgG subclass levels using immunonephelometry in serum samples from participants enrolled in two previous COPD trials: Macrolide Azithromycin for Prevention of Exacerbations of COPD (MACRO; n = 976) and Simvastatin for the Prevention of Exacerbations in Moderate-to-Severe COPD (STATCOPE; n = 653). All samples were collected from clinically stable participants upon entry into both studies. IgG subclass deficiency was diagnosed when IgG subclass levels were below their respective lower limit of normal: IgG1 < 2.8 g/L; IgG2 < 1.15 g/L; IgG3 < 0.24 g/L; and IgG4 < 0.052 g/L. To investigate the impact of IgG subclass levels on time to first exacerbation or hospitalization, we log-transformed IgG levels and performed Cox regression models, with adjustments for confounders. One or more IgG subclass deficiencies were found in 173 (17.7%) and 133 (20.4%) participants in MACRO and STATCOPE, respectively. Lower IgG1 or IgG2 levels resulted in increased risk of exacerbations with adjusted hazard ratios (HR) of 1.30 (95% CI, 1.10-1.54, p < 0.01) and 1.19 (95% CI, 1.05-1.35, p < 0.01), respectively in the MACRO study, with STATCOPE yielding similar results. Reduced IgG1 or IgG2 levels were also associated with increased risk of hospitalizations: the adjusted HR for IgG1 and IgG2 was 1.52 (95% CI: 1.15-2.02, p < 0.01) and 1.33 (95% CI, 1.08-1.64, p < 0.01), respectively for the MACRO study; in STATCOPE, only IgG2 was an independent predictor of hospitalization. In our multivariate Cox models, IgG3 and IgG4 levels did not result in significant associations for both outcomes in either MACRO or STATCOPE cohorts. Approximately 1 in 5 COPD patients had one or more IgG subclass deficiencies. Reduced IgG subclass levels were independent risk factors for both COPD exacerbations (IgG1 and IgG2) and hospitalizations (IgG2) in two COPD cohorts. This study used serum samples from participants of the MACRO ( NCT00325897 ) and STATCOPE ( NCT01061671 ) trials.

NAVAIR Portable Source Initiative (NPSI) Standard for Material Properties Reference Database (MPRD) V2.2

DTIC Science & Technology

2012-09-26

format; however, the collective identity and structure of the object are lost. In contrast, XML preserves the structure of the object by using custom...2.1.1 Classes  ROCK  SOIL  MINERAL  VEGETATION  COATING  LIQUID  METAL  CONSTRUCTION  PLASTIC  WOOD  GLASS  FABRIC...2.1.2 Subclasses Subclasses are created using relevant taxonomy from the authority in a particular class. Some examples of subclasses nomenclature in

IgG Donor-Specific Anti-Human HLA Antibody Subclasses and Kidney Allograft Antibody-Mediated Injury.

PubMed

Lefaucheur, Carmen; Viglietti, Denis; Bentlejewski, Carol; Duong van Huyen, Jean-Paul; Vernerey, Dewi; Aubert, Olivier; Verine, Jérôme; Jouven, Xavier; Legendre, Christophe; Glotz, Denis; Loupy, Alexandre; Zeevi, Adriana

2016-01-01

Antibodies may have different pathogenicities according to IgG subclass. We investigated the association between IgG subclasses of circulating anti-human HLA antibodies and antibody-mediated kidney allograft injury. Among 635 consecutive kidney transplantations performed between 2008 and 2010, we enrolled 125 patients with donor-specific anti-human HLA antibodies (DSA) detected in the first year post-transplant. We assessed DSA characteristics, including specificity, HLA class specificity, mean fluorescence intensity (MFI), C1q-binding, and IgG subclass, and graft injury phenotype at the time of sera evaluation. Overall, 51 (40.8%) patients had acute antibody-mediated rejection (aABMR), 36 (28.8%) patients had subclinical ABMR (sABMR), and 38 (30.4%) patients were ABMR-free. The MFI of the immunodominant DSA (iDSA, the DSA with the highest MFI level) was 6724±464, and 41.6% of patients had iDSA showing C1q positivity. The distribution of iDSA IgG1-4 subclasses among the population was 75.2%, 44.0%, 28.0%, and 26.4%, respectively. An unsupervised principal component analysis integrating iDSA IgG subclasses revealed aABMR was mainly driven by IgG3 iDSA, whereas sABMR was driven by IgG4 iDSA. IgG3 iDSA was associated with a shorter time to rejection (P<0.001), increased microcirculation injury (P=0.002), and C4d capillary deposition (P<0.001). IgG4 iDSA was associated with later allograft injury with increased allograft glomerulopathy and interstitial fibrosis/tubular atrophy lesions (P<0.001 for all comparisons). Integrating iDSA HLA class specificity, MFI level, C1q-binding status, and IgG subclasses in a Cox survival model revealed IgG3 iDSA and C1q-binding iDSA were strongly and independently associated with allograft failure. These results suggest IgG iDSA subclasses identify distinct phenotypes of kidney allograft antibody-mediated injury. Copyright © 2016 by the American Society of Nephrology.

SUPPRESSION OF THE EPITHELIAL-MESENCHYMAL TRANSITION BY GRAINYHEAD-LIKE-2

PubMed Central

Cieply, Benjamin; Riley, Philip; Pifer, Phillip M.; Widmeyer, Joseph; Addison, Joseph B.; Ivanov, Alexey V.; Denvir, James; Frisch, Steven M.

2012-01-01

Grainyhead genes are involved in wound healing and developmental neural tube closure. In light of the high degree of similarity between the epithelial-mesenchymal transitions (EMT) occurring in wound healing processes and the cancer stem cell-like compartment of tumors, including TGF-β-dependence, we investigated the role of the Grainyhead gene, Grainyhead-Like-2 (GRHL2) in oncogenic EMT. GRHL2 was down-regulated specifically in the claudin-low subclass breast tumors and in basal-B subclass breast cancer cell lines. GRHL2 suppressed TGF-β-induced, Twist-induced or spontaneous EMT, enhanced anoikis-sensitivity, and suppressed mammosphere generation in mammary epithelial cells. These effects were mediated in part by suppression of ZEB1 expression via direct repression of the ZEB1 promoter. GRHL2 also inhibited Smad-mediated transcription and it upregulated mir200b/c as well as the TGF-β receptor antagonist, BMP2. Lastly, ectopic expression of GRHL2 in MDA-MB-231 breast cancer cells triggered a mesenchymal-to-epithelial transition and restored sensitivity to anoikis. Taken together, our findings define a major role for GRHL2 in the suppression of oncogenic EMT in breast cancer cells. PMID:22379025

Diversity of fatty acid composition of symbiotic dinoflagellates in corals: evidence for the transfer of host PUFAs to the symbionts.

PubMed

Imbs, Andrey B; Yakovleva, Irina M; Dautova, Tatiana N; Bui, Long H; Jones, Paul

2014-05-01

High diversity of fatty acid (FA) composition of endosymbiotic dinoflagellates of the Symbiodinium group (zooxanthellae) isolated from different cnidarian groups has been found. To explain this diversity, FA composition of the total lipids of pure symbiont fractions (SF) and host cell tissue fractions (HF) isolated from one hydrocoral, two soft coral, and seven hard coral species inhabiting the shallow waters of the South China Sea (Vietnam) were compared. Symbiodinium phylogenetic clade designation for each SF was also determined, however, the relationship between the clade designation and FA composition of Symbiodinium was not found. The profiles of marker polyunsaturated FAs (PUFAs) of symbionts (18:4n-3, 18:5n-3, 20:5n-3) did not depend on taxonomic designation of the host and reflected only a specimen-specific diversity of the SF lipids. Several FAs such as 20:0, C24 PUFAs, 22:5n-6, and 18:2n-7 concentrated in HF lipids but were also found in SF lipids. For ten cnidarian species studied, the principal components analysis of total FAs (27 variables) of the symbiotic fractions was performed. The clear division of the symbiotic dinoflagellates according to the host systematic identity was found on a subclass level. This division was mainly caused by the FAs specific for the host lipids of each cnidarian subclasses such as hard corals, soft corals, and hydrocorals. Thus, the coral hosts affect the FA profile of their symbionts and cause the diversity of FA composition of Symbiodinium. The transfer of FAs from the coral host to their symbiotic dinoflagellates and modulation of PUFA biosynthesis in symbionts by the host are considered as possible reasons of the diversity studied. Copyright © 2014 Elsevier Ltd. All rights reserved.

Insights into plant cell wall structure, architecture, and integrity using glycome profiling of native and AFEXTM-pre-treated biomass

PubMed Central

Pattathil, Sivakumar; Hahn, Michael G.; Dale, Bruce E.; Chundawat, Shishir P. S.

2015-01-01

Cell walls, which constitute the bulk of plant biomass, vary considerably in their structure, composition, and architecture. Studies on plant cell walls can be conducted on both native and pre-treated plant biomass samples, allowing an enhanced understanding of these structural and compositional variations. Here glycome profiling was employed to determine the relative abundance of matrix polysaccharides in several phylogenetically distinct native and pre-treated plant biomasses. Eight distinct biomass types belonging to four different subgroups (i.e. monocot grasses, woody dicots, herbaceous dicots, and softwoods) were subjected to various regimes of AFEX™ (ammonia fiber expansion) pre-treatment [AFEX is a trademark of MBI, Lansing (http://www.mbi.org]. This approach allowed detailed analysis of close to 200 cell wall glycan epitopes and their relative extractability using a high-throughput platform. In general, irrespective of the phylogenetic origin, AFEX™ pre-treatment appeared to cause loosening and improved accessibility of various xylan epitope subclasses in most plant biomass materials studied. For most biomass types analysed, such loosening was also evident for other major non-cellulosic components including subclasses of pectin and xyloglucan epitopes. The studies also demonstrate that AFEX™ pre-treatment significantly reduced cell wall recalcitrance among diverse phylogenies (except softwoods) by inducing structural modifications to polysaccharides that were not detectable by conventional gross composition analyses. It was found that monitoring changes in cell wall glycan compositions and their relative extractability for untreated and pre-treated plant biomass can provide an improved understanding of variations in structure and composition of plant cell walls and delineate the role(s) of matrix polysaccharides in cell wall recalcitrance. PMID:25911738

Insights into plant cell wall structure, architecture, and integrity using glycome profiling of native and AFEX TM -pre-treated biomass

DOE PAGES

Pattathil, Sivakumar; Hahn, Michael G.; Dale, Bruce E.; ...

2015-04-23

We report that cell walls, which constitute the bulk of plant biomass, vary considerably in their structure, composition, and architecture. Studies on plant cell walls can be conducted on both native and pre-treated plant biomass samples, allowing an enhanced understanding of these structural and compositional variations. Here glycome profiling was employed to determine the relative abundance of matrix polysaccharides in several phylogenetically distinct native and pre-treated plant biomasses. Eight distinct biomass types belonging to four different subgroups (i.e. monocot grasses, woody dicots, herbaceous dicots, and softwoods) were subjected to various regimes of AFEX™ (ammonia fiber expansion) pre-treatment [AFEX is amore » trademark of MBI, Lansing (http://www.mbi.org]. This approach allowed detailed analysis of close to 200 cell wall glycan epitopes and their relative extractability using a high-throughput platform. In general, irrespective of the phylogenetic origin, AFEX™ pre-treatment appeared to cause loosening and improved accessibility of various xylan epitope subclasses in most plant biomass materials studied. For most biomass types analysed, such loosening was also evident for other major non-cellulosic components including subclasses of pectin and xyloglucan epitopes. The studies also demonstrate that AFEX™ pre-treatment significantly reduced cell wall recalcitrance among diverse phylogenies (except softwoods) by inducing structural modifications to polysaccharides that were not detectable by conventional gross composition analyses. Lastly, we found that monitoring changes in cell wall glycan compositions and their relative extractability for untreated and pre-treated plant biomass can provide an improved understanding of variations in structure and composition of plant cell walls and delineate the role(s) of matrix polysaccharides in cell wall recalcitrance.« less

Identification and Expression Analysis of Polygalacturonase Family Members during Peach Fruit Softening.

PubMed

Qian, Ming; Zhang, Yike; Yan, Xiangyan; Han, Mingyu; Li, Jinjin; Li, Fang; Li, Furui; Zhang, Dong; Zhao, Caiping

2016-11-18

Polygalacturonase (PG) is an important hydrolytic enzyme involved in pectin degradation during fruit softening. However, the roles of PG family members in fruit softening remain unclear. We identified 45 PpPG genes in the peach genome which are clustered into six subclasses. PpPGs consist of four to nine exons and three to eight introns, and the exon/intron structure is basically conserved in all but subclass E. Only 16 PpPG genes were expressed in ripening fruit, and their expression profiles were analyzed during storage in two peach cultivars with different softening characteristics. Eight PGs ( PpPG1 , - 10 , - 12 , - 13 , - 15 , - 23 , - 21 , and - 22 ) in fast-softening "Qian Jian Bai" (QJB) fruit and three PGs ( PpPG15 , - 21 , and - 22 ) in slow-softening "Qin Wang" (QW) fruit exhibited softening-associated patterns; which also were affected by ethylene treatment. Our results suggest that the different softening characters in QW and QJB fruit is related to the amount of PG members. While keeping relatively lower levels during QW fruit softening, the expression of six PGs ( PpPG1 , - 10 , - 12 , - 11 , - 14 , and - 35 ) rapidly induced by ethylene. PpPG24 , - 25 and - 38 may not be involved in softening of peach fruit.

Influence of IgG Subclass on Human Antimannan Antibody-Mediated Resistance to Hematogenously Disseminated Candidiasis in Mice

PubMed Central

Nishiya, Casey T.; Boxx, Gayle M.; Robison, Kerry; Itatani, Carol; Kozel, Thomas R.

2015-01-01

Candida albicans is a yeast-like pathogen and can cause life-threatening systemic candidiasis. Its cell surface is enriched with mannan that is resistant to complement activation. Previously, we developed the recombinant human IgG1 antimannan antibody M1g1. M1g1 was found to promote complement activation and phagocytosis and protect mice from systemic candidiasis. Here, we evaluate the influence of IgG subclass on antimannan antibody-mediated protection. Three IgG subclass variants of M1g1 were constructed: M1g2, M1g3, and M1g4. The IgG subclass identity for each variant was confirmed with DNA sequence and subclass-specific antibodies. These variants contain identical M1 Fabs and exhibited similar binding affinities for C. albicans yeast and purified mannan. Yeast cells and hyphae recovered from the kidney of antibody-treated mice with systemic candidiasis showed uniform binding of each variant, indicating constitutive expression of the M1 epitope and antibody opsonization in the kidney. All variants promoted deposition of both murine and human C3 onto the yeast cell surface, with M1g4 showing delayed activation, as determined by flow cytometry and immunofluorescence microscopy. M1g4-mediated complement activation was found to be associated with its M1 Fab that activates the alternative pathway in an Fc-independent manner. Treatment with each subclass variant extended the survival of mice with systemic candidiasis (P < 0.001). However, treatment with M1g1, M1g3, or M1g4, but not with M1g2, also reduced the kidney fungal burden (P < 0.001). Thus, the role of human antimannan antibody in host resistance to systemic candidiasis is influenced by its IgG subclass. PMID:26573736

Measurement of food flavonoids by high-performance liquid chromatography: A review.

PubMed

Merken, H M; Beecher, G R

2000-03-01

The flavonoids are plant polyphenols found frequently in fruits, vegetables, and grains. Divided into several subclasses, they include the anthocyanidins, pigments chiefly responsible for the red and blue colors in fruits, fruit juices, wines, and flowers; the catechins, concentrated in tea; the flavanones and flavanone glycosides, found in citrus and honey; and the flavones, flavonols, and flavonol glycosides, found in tea, fruits, vegetables, and honey. Known for their hydrogen-donating antioxidant activity as well as their ability to complex divalent transition metal cations, flavonoids are propitious to human health. Computer-controlled high-performance liquid chromatography (HPLC) has become the analytical method of choice. Many systems have been developed for the detection and quantification of flavonoids across one, two, or three subclasses. A summary of the various HPLC and sample preparation methods that have been employed to quantify individual flavonoids within a subclass or across several subclasses are tabulated in this review.

Comprehensive Lipidome-Wide Profiling Reveals Dynamic Changes of Tea Lipids during Manufacturing Process of Black Tea.

PubMed

Li, Jia; Hua, Jinjie; Zhou, Qinghua; Dong, Chunwang; Wang, Jinjin; Deng, Yuliang; Yuan, Haibo; Jiang, Yongwen

2017-11-22

As important biomolecules in Camellia sinensis L., lipids undergo substantial changes during black tea manufacture, which is considered to contribute to tea sensory quality. However, limited by analytical capacity, detailed lipid composition and its dynamic changes during black tea manufacture remain unclear. Herein, we performed tea lipidome profiling using high resolution liquid chromatography coupled to mass spectrometry (LC-MS), which allows simultaneous and robust analysis of 192 individual lipid species in black tea, covering 17 (sub)classes. Furthermore, dynamic changes of tea lipids during black tea manufacture were investigated. Significant alterations of lipid pattern were revealed, involved with chlorophyll degradation, metabolic pathways of glycoglycerolipids, and other extraplastidial membrane lipids. To our knowledge, this report presented most comprehensive coverage of lipid species in black tea. This study provides a global and in-depth metabolic map of tea lipidome during black tea manufacture.

Profiling the Phenolic Compounds of the Four Major Seed Coat Types and Their Relation to Color Genes in Lentil.

PubMed

Mirali, Mahla; Purves, Randy W; Vandenberg, Albert

2017-05-26

Phenolic compounds can provide antioxidant health benefits for humans, and foods such as lentils can be valuable dietary sources of different subclasses of these secondary metabolites. This study used LC-MS analyses to compare the phenolic profiles of lentil genotypes with four seed coat background colors (green, gray, tan, and brown) and two cotyledon colors (red and yellow) grown at two locations. The mean area ratio per mg sample (MARS) values of various phenolic compounds in lentil seeds varied with the different seed coat colors conferred by specific genotypes. Seed coats of lentil genotypes with the homozygous recessive tgc allele (green and gray seed coats) had higher MARS values of flavan-3-ols, proanthocyanidins, and some flavonols. This suggests lentils featuring green and gray seed coats might be more promising as health-promoting foods.

Age related IgG subclass concentrations in asthma.

PubMed

Hoeger, P H; Niggemann, B; Haeuser, G

1994-03-01

The prevalence of IgG subclass deficiency in asthma is still controversial. Earlier studies often included patients receiving treatment with systemic steroids which can induce hypogammaglobulinaemia. Concentrations of IgG subclasses were studies in 200 children (aged 2-17 years) with asthma (mean asthma severity score (ASS) 2, range 1-4) who had not received systemic steroids for at least six weeks before investigation, and in 226 healthy age matched controls. The mean concentrations of IgG subclasses in children with asthma were within the 1SD range of those of the control group. In the group with asthma there was a trend towards higher levels of IgG1 and IgG4, whereas the number of children with low concentrations of IgG2 (< 2 SD of control serum samples; absolute concentrations 0.08-1.25 g/l) was slightly greater than in the group who did not have asthma (4.5 v 2.2%). Patients with subnormal concentrations of IgG2 could not be distinguished clinically or on the basis of case history and additional immunological studies did not show further abnormalities. Patients with severe asthma (ASS 3-4) had significantly higher concentrations of IgG4 (mean (SE) 0.53 (0.09) v 0.26 (0.04) g/l) than patients with mild asthma (ASS 1). No significant difference in subclass concentration was found between patients with atopic and those with non-atopic asthma. It is concluded that in an unselected group of children with asthma the mean IgG subclass concentrations do not differ significantly from a group of healthy age matched controls.

An overview of the kinetic parameters of class B beta-lactamases.

PubMed Central

Felici, A; Amicosante, G; Oratore, A; Strom, R; Ledent, P; Joris, B; Fanuel, L; Frère, J M

1993-01-01

The catalytic properties of three class B beta-lactamases (from Pseudomonas maltophilia, Aeromonas hydrophila and Bacillus cereus) were studied and compared with those of the Bacteroides fragilis enzyme. The A. hydrophila beta-lactamase exhibited a unique specificity profile and could be considered as a rather specific 'carbapenemase'. No relationships were found between sequence similarities and catalytic properties. The problem of the repartition of class B beta-lactamases into sub-classes is discussed. Improved purification methods were devised for the P. maltophilia and A. hydrophila beta-lactamases including, for the latter enzyme, a very efficient affinity chromatography step on a Zn(2+)-chelate column. Images Figure 1 PMID:8471035

A flexible and rapid frequency selective scheme for SRS microscopy

NASA Astrophysics Data System (ADS)

Li, Jingting; Yue, Yuankai; Shih, Wei-Chuan

2017-02-01

Stimulated Raman scattering (SRS) is a label-free imaging technique suitable for studying biological systems. Due to stimulated nature by ultrafast laser pulses, SRS microscopy has the advantage of significantly higher sensitivity but often reduced spectroscopic information. In this paper, we present a newly constructed femtosecond SRS microscope with a high-speed dynamic micromirror device based pulse shaper to achieve flexible and rapid frequency selection within the C-H stretch region near 2800 to 3100 cm-1 with spectral width of 30 cm-1. This technique is applicable to lipid profiling such as cell activity mapping, lipid distribution mapping and distinction among subclasses.

A prominent large high-density lipoprotein at birth enriched in apolipoprotein C-I identifies a new group of infancts of lower birth weight and younger gestational age

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kwiterovich Jr., Peter O.; Cockrill, Steven L.; Virgil, Donna G.

2003-10-01

Because low birth weight is associated with adverse cardiovascular risk and death in adults, lipoprotein heterogeneity at birth was studied. A prominent, large high-density lipoprotein (HDL) subclass enriched in apolipoprotein C-I (apoC-I) was found in 19 percent of infants, who had significantly lower birth weights and younger gestational ages and distinctly different lipoprotein profiles than infants with undetectable, possible or probable amounts of apoC-I-enriched HDL. An elevated amount of an apoC-I-enriched HDL identifies a new group of low birth weight infants.

Genetics of non-conventional lipoprotein fractions

USDA-ARS?s Scientific Manuscript database

Lipoprotein subclass measures associate with cardiometabolic disease risk. Currently the information that lipoproteins convey on disease risk over that of traditional demographic and lipid measures is minimal, and so their use is clinics is limited. However, lipoprotein subclass perturbations repres...

Characterization of ROS1 cDNA from a human glioblastoma cell line

DOE Office of Scientific and Technical Information (OSTI.GOV)

Birchmeier, C.; O'Neill, K.; Riggs, M.

1990-06-01

The authors have isolated and characterized a human ROS1 cDNA from the glioblastoma cell line SW-1088. The cDNA, 8.3 kilobases long, has the potential to encode a transmembrane tyrosine-specific protein kinase with a predicted molecular mass of 259 kDa. The putative extracellular domain of ROS1 is homologous to the extracellular domain of the sevenless gene product from Drosophila. No comparable similarities in the extracellular domains were found between ROS1 and other receptor-type tyrosine kinases. Together, ROS1 and sevenless gene products define a distinct subclass of transmember tyrosine kinases.

“Quantumness” versus “classicality” of quantum states and quantum protocols

NASA Astrophysics Data System (ADS)

Brodutch, Aharon; Groisman, Berry; Kenigsberg, Dan; Mor, Tal

Entanglement is one of the pillars of quantum mechanics and quantum information processing, and as a result, the quantumness of nonentangled states has typically been overlooked and unrecognized until the last decade. We give a robust definition for the classicality versus quantumness of a single multipartite quantum state, a set of states, and a protocol using quantum states. We show a variety of nonentangled (separable) states that exhibit interesting quantum properties, and we explore the “zoo” of separable states; several interesting subclasses are defined based on the diagonalizing bases of the states, and their nonclassical behavior is investigated.

Subclass distribution of IgG antibodies to the rat oesophagus stratum corneum (so-called anti-keratin antibodies) in rheumatoid arthritis.

PubMed Central

Vincent, C; Serre, G; Basile, J P; Lestra, H C; Girbal, E; Sebbag, M; Soleilhavoup, J P

1990-01-01

Serum IgG, labelling the stratum corneum of the rat oesophagus epithelium, so-called anti-keratin antibodies (AKA) constitute the most specific marker for the diagnosis of rheumatoid arthritis. In this study, we investigated 31 IgG AKA-positive rheumatoid sera and 21 control sera from patients with non-rheumatoid inflammatory rheumatic diseases. The serum level of IgG1,2,3 and 4 was determined by radial immunodiffusion and the subclass distribution of IgG AKA by a three-step semi-quantitative immunofluorescence assay using standard monoclonal antibodies specific for each of the four human IgG subclasses. In the rheumatoid sera, the serum level of IgG1 was found to be significantly increased and the level of IgG2 significantly decreased with regard to the control sera, while the levels of IgG3 and 4 as well as total IgG were in the normal range. IgG1,2,3, and 4 AKA were detected in 27 (87%), 6 (19%), 4 (13%) and 11 (35%) of the 31 rheumatoid sera, respectively, and were found to be independent of the clinical and biological indices of the disease. In spite of inter-individual heterogeneity, two predominant profiles were distinguished: IgG1 (alone) and IgG(1 + 4), which together represented 18 sera (58%). The large predominance of IgG1 AKA and the quasi-absence of IgG2 AKA suggest that the recognized antigen may be partly comprised of protein. Moreover, the high frequency of occurrence of IgG4 AKA might result from chronic exposure to the eliciting antigen, which could be a genuine autoantigen since we demonstrated that it is also present in the stratum corneum of human epidermis. Images Fig. 1 PMID:1696185

Tumour-associated glial host cells display a stem-like phenotype with a distinct gene expression profile and promote growth of GBM xenografts.

PubMed

Leiss, Lina; Mutlu, Ercan; Øyan, Anne; Yan, Tao; Tsinkalovsky, Oleg; Sleire, Linda; Petersen, Kjell; Rahman, Mohummad Aminur; Johannessen, Mireille; Mitra, Sidhartha S; Jacobsen, Hege K; Talasila, Krishna M; Miletic, Hrvoje; Jonassen, Inge; Li, Xingang; Brons, Nicolaas H; Kalland, Karl-Henning; Wang, Jian; Enger, Per Øyvind

2017-02-07

Little is known about the role of glial host cells in brain tumours. However, supporting stromal cells have been shown to foster tumour growth in other cancers. We isolated stromal cells from patient-derived glioblastoma (GBM) xenografts established in GFP-NOD/scid mice. With simultaneous removal of CD11b + immune and CD31 + endothelial cells by fluorescence activated cell sorting (FACS), we obtained a population of tumour-associated glial cells, TAGs, expressing markers of terminally differentiaed glial cell types or glial progenitors. This cell population was subsequently characterised using gene expression analyses and immunocytochemistry. Furthermore, sphere formation was assessed in vitro and their glioma growth-promoting ability was examined in vivo. Finally, the expression of TAG related markers was validated in human GBMs. TAGs were highly enriched for the expression of glial cell proteins including GFAP and myelin basic protein (MBP), and immature markers such as Nestin and O4. A fraction of TAGs displayed sphere formation in stem cell medium. Moreover, TAGs promoted brain tumour growth in vivo when co-implanted with glioma cells, compared to implanting only glioma cells, or glioma cells and unconditioned glial cells from mice without tumours. Genome-wide microarray analysis of TAGs showed an expression profile distinct from glial cells from healthy mice brains. Notably, TAGs upregulated genes associated with immature cell types and self-renewal, including Pou3f2 and Sox2. In addition, TAGs from highly angiogenic tumours showed upregulation of angiogenic factors, including Vegf and Angiopoietin 2. Immunohistochemistry of three GBMs, two patient biopsies and one GBM xenograft, confirmed that the expression of these genes was mainly confined to TAGs in the tumour bed. Furthermore, their expression profiles displayed a significant overlap with gene clusters defining prognostic subclasses of human GBMs. Our data demonstrate that glial host cells in brain tumours are functionally distinct from glial cells of healthy mice brains. Furthermore, TAGs display a gene expression profile with enrichment for genes related to stem cells, immature cell types and developmental processes. Future studies are needed to delineate the biological mechanisms regulating the brain tumour-host interplay.

16 CFR 1025.18 - Class actions.

Code of Federal Regulations, 2014 CFR

2014-01-01

... Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION GENERAL RULES OF PRACTICE FOR ADJUDICATIVE..., regulation, or consumer product safety rule, or (3) Manufacturers, distributors, or retailers, or a... consumer product safety rule. When appropriate, a class may be divided into subclasses and each subclass...

16 CFR § 1025.18 - Class actions.

Code of Federal Regulations, 2013 CFR

2013-01-01

... Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION GENERAL RULES OF PRACTICE FOR ADJUDICATIVE..., regulation, or consumer product safety rule, or (3) Manufacturers, distributors, or retailers, or a... consumer product safety rule. When appropriate, a class may be divided into subclasses and each subclass...

16 CFR 1025.18 - Class actions.

Code of Federal Regulations, 2012 CFR

2012-01-01

... Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION GENERAL RULES OF PRACTICE FOR ADJUDICATIVE..., regulation, or consumer product safety rule, or (3) Manufacturers, distributors, or retailers, or a... consumer product safety rule. When appropriate, a class may be divided into subclasses and each subclass...

An Object-oriented Taxonomy of Medical Data Presentations

PubMed Central

Starren, Justin; Johnson, Stephen B.

2000-01-01

A variety of methods have been proposed for presenting medical data visually on computers. Discussion of and comparison among these methods have been hindered by a lack of consistent terminology. A taxonomy of medical data presentations based on object-oriented user interface principles is presented. Presentations are divided into five major classes—list, table, graph, icon, and generated text. These are subdivided into eight subclasses with simple inheritance and four subclasses with multiple inheritance. The various subclasses are reviewed and examples are provided. Issues critical to the development and evaluation of presentations are also discussed. PMID:10641959

Metabolic signatures of adiposity in young adults: Mendelian randomization analysis and effects of weight change.

PubMed

Würtz, Peter; Wang, Qin; Kangas, Antti J; Richmond, Rebecca C; Skarp, Joni; Tiainen, Mika; Tynkkynen, Tuulia; Soininen, Pasi; Havulinna, Aki S; Kaakinen, Marika; Viikari, Jorma S; Savolainen, Markku J; Kähönen, Mika; Lehtimäki, Terho; Männistö, Satu; Blankenberg, Stefan; Zeller, Tanja; Laitinen, Jaana; Pouta, Anneli; Mäntyselkä, Pekka; Vanhala, Mauno; Elliott, Paul; Pietiläinen, Kirsi H; Ripatti, Samuli; Salomaa, Veikko; Raitakari, Olli T; Järvelin, Marjo-Riitta; Smith, George Davey; Ala-Korpela, Mika

2014-12-01

Increased adiposity is linked with higher risk for cardiometabolic diseases. We aimed to determine to what extent elevated body mass index (BMI) within the normal weight range has causal effects on the detailed systemic metabolite profile in early adulthood. We used Mendelian randomization to estimate causal effects of BMI on 82 metabolic measures in 12,664 adolescents and young adults from four population-based cohorts in Finland (mean age 26 y, range 16-39 y; 51% women; mean ± standard deviation BMI 24 ± 4 kg/m(2)). Circulating metabolites were quantified by high-throughput nuclear magnetic resonance metabolomics and biochemical assays. In cross-sectional analyses, elevated BMI was adversely associated with cardiometabolic risk markers throughout the systemic metabolite profile, including lipoprotein subclasses, fatty acid composition, amino acids, inflammatory markers, and various hormones (p<0.0005 for 68 measures). Metabolite associations with BMI were generally stronger for men than for women (median 136%, interquartile range 125%-183%). A gene score for predisposition to elevated BMI, composed of 32 established genetic correlates, was used as the instrument to assess causality. Causal effects of elevated BMI closely matched observational estimates (correspondence 87% ± 3%; R(2)= 0.89), suggesting causative influences of adiposity on the levels of numerous metabolites (p<0.0005 for 24 measures), including lipoprotein lipid subclasses and particle size, branched-chain and aromatic amino acids, and inflammation-related glycoprotein acetyls. Causal analyses of certain metabolites and potential sex differences warrant stronger statistical power. Metabolite changes associated with change in BMI during 6 y of follow-up were examined for 1,488 individuals. Change in BMI was accompanied by widespread metabolite changes, which had an association pattern similar to that of the cross-sectional observations, yet with greater metabolic effects (correspondence 160% ± 2%; R(2) = 0.92). Mendelian randomization indicates causal adverse effects of increased adiposity with multiple cardiometabolic risk markers across the metabolite profile in adolescents and young adults within the non-obese weight range. Consistent with the causal influences of adiposity, weight changes were paralleled by extensive metabolic changes, suggesting a broadly modifiable systemic metabolite profile in early adulthood. Please see later in the article for the Editors' Summary.

Soil profile of Yellow-brown Earth overlying Red Clay in southern Anhui Province: A pedogenic response to the Last Glacial - Interglacial cycle in mid-subtropical China

NASA Astrophysics Data System (ADS)

Hu, Xue-Feng; Du, Yan

2013-04-01

Soil profile of Yellow-brown Earth (YBE) overlying Red Clay (RC) is commonly seen along the Yangtze River in mid-subtropical China. To study its paleoclimatic implications, one YBE - RC profile in Langxi county, southern Anhui Province, were dated with the optically stimulated luminescence (OSL) method in detail. The results indicated that the dual - layered profile is actually a pedogenic response to a great climatic change during the Last Glacial - Last Interglacial cycle: The YBE is homogenous to the aeolian Xiashu Loess widely distributed along the Yangtze River and was dated from 12.2 ka to 57.1 ka; and the underlying RC approximately from 60 ka to 132.8 ka, which fully suggests that the YBE is really the Last Glacial loess, correlated with the Malan Loess in the Chinese Loess Plateau, Northwest China, and the RC was mainly formed during the Last Interglacial. Two sub-class events of the Last Glacial, the Last Glacial Maximum (LGM) and the Last Glacial Optimum (LGO), correlated with the marine oxygen isotopic stage (MIS) 2 and 3, can be separated and identified in the YBE. Likewise, the RC can be divided into the Uniform Red Clay (URC) and Reticulate Red Clay (RRC). The URC was formed during the transitional time from the Last Interglacial to the Last Glacial, and the RRC mainly during the Last Interglacial, MIS 5. The RC is highly weathered but still shows aeolian-dust characteristics. The duplicate information implies that the paleoclimate during the Last Interglacial is instable and might also oscillate between warm and cold, but sub-class paleoclimatic events, potential correlated with MIS 5 a - 5 e, cannot be identified in the RRC possibly due to the overlapped paleoclimatic information caused by highly chemical weathering. A great climatic transfer during the Last Glacial - Interglacial cycle left soil parent materials diversified in the study areas and hence caused the parallel distribution of different zonal soils in a small scale. Two surface soils, Yellow-brown Soils (Acrisols), derived from the YBE, and Red Soils (Plinthosols), derived from the RC, often coexist in the areas. The Red Soils are really relict and not correlated with the current soil-forming conditions. Sometimes, the influence of climatic change on the pedogenesis is so significant that it should never be neglected.

Application of Ontology Technology in Health Statistic Data Analysis.

PubMed

Guo, Minjiang; Hu, Hongpu; Lei, Xingyun

2017-01-01

Research Purpose: establish health management ontology for analysis of health statistic data. Proposed Methods: this paper established health management ontology based on the analysis of the concepts in China Health Statistics Yearbook, and used protégé to define the syntactic and semantic structure of health statistical data. six classes of top-level ontology concepts and their subclasses had been extracted and the object properties and data properties were defined to establish the construction of these classes. By ontology instantiation, we can integrate multi-source heterogeneous data and enable administrators to have an overall understanding and analysis of the health statistic data. ontology technology provides a comprehensive and unified information integration structure of the health management domain and lays a foundation for the efficient analysis of multi-source and heterogeneous health system management data and enhancement of the management efficiency.

Guiding Chiral Self-Propellers in a Periodic Potential

NASA Astrophysics Data System (ADS)

Nourhani, Amir; Crespi, Vincent H.; Lammert, Paul E.

2015-09-01

Ingenious suggestions continue to be made for separation of racemic mixtures according to the inert structural chirality of the constituents. Recently discovered self-motile micro- or nanoparticles express dynamical chirality, i.e., that which originates in motion, not structure. Here, we predict how dynamically chiral objects, with overdamped dynamics in a soft periodic two-dimensional potential, can display not only separation into well-defined dynamical subclasses defined by motility characteristics, but also the ability to be steered to arbitrary locations in the plane by simply changing the amplitude of the external potential. Orientational and translational diffusion produce new types of drift absent in the noise-free case. As practical implementation seems feasible with acoustic or optical fields, these phenomena can be useful for laboratory microscales manipulations, possibly including reconfigurable microfluidic circuits with complex networks of unidirectional channels.

Particle numbers of lipoprotein subclasses and arterial stiffness among middle-aged men from the ERA JUMP study.

PubMed

Vishnu, A; Choo, J; Masaki, K H; Mackey, R H; Barinas-Mitchell, E; Shin, C; Willcox, B J; El-Saed, A; Seto, T B; Fujiyoshi, A; Miura, K; Lee, S; Sutton-Tyrrell, K; Kuller, L H; Ueshima, H; Sekikawa, A

2014-02-01

We examined the association between serum lipoprotein subclasses and the three measures of arterial stiffness, that is, (i) carotid-femoral pulse wave velocity (cfPWV), which is a gold standard measure of central arterial stiffness, (ii) brachial-ankle PWV (baPWV), which is emerging as a combined measure of central and peripheral arterial stiffness and (iii) femoral-ankle PWV (faPWV), which is a measure of peripheral arterial stiffness. Among a population-based sample of 701 apparently healthy Caucasian, Japanese American and Korean men aged 40-49 years, concentrations of lipoprotein particles were assessed by nuclear magnetic resonance (NMR) spectroscopy, and the PWV was assessed with an automated waveform analyzer (VP2000, Omron, Japan). Multiple linear regressions were performed to analyse the association between each NMR lipoprotein subclasses and PWV measures, after adjusting for cardiovascular risk factors and other confounders. A cutoff of P<0.01 was used for determining significance. All PWV measures had significant correlations with total and small low-density lipoprotein particle number (LDL-P) (all P<0.0001) but not LDL cholesterol (LDL-C) (all P>0.1), independent of race and age. In multivariate regression analysis, no NMR lipoprotein subclass was significantly associated with cfPWV (all P>0.01). However, most NMR lipoprotein subclasses had significant associations with both baPWV and faPWV (P<0.01). In this study of healthy middle-aged men, as compared with cfPWV, both baPWV and faPWV had stronger associations with particle numbers of lipoprotein subclasses. Our results may suggest that both baPWV and faPWV are related to arterial stiffness and atherosclerosis, whereas cfPWV may represent arterial stiffness alone.

Differential Decline in Leishmania Membrane Antigen-Specific Immunoglobulin G (IgG), IgM, IgE, and IgG Subclass Antibodies in Indian Kala-Azar Patients after Chemotherapy

PubMed Central

Anam, Khairul; Afrin, Farhat; Banerjee, Dwijadas; Pramanik, Netai; Guha, Subhasis K.; Goswami, Rama P.; Saha, Shiben K.; Ali, Nahid

1999-01-01

Pathogenesis in kala-azar is associated with depressed cellular immunity and significant elevation of antileishmanial antibodies. Since these antibodies are present even after cure, analysis of the parasite-specific isotypes and immunoglobulin G (IgG) subclasses in kala-azar patients may shed new light on the immune responses during progression and resolution of infection. Using leishmanial membrane antigenic extracts, we investigated the relative levels of specific IgG, IgM, IgA, IgE, and IgG subclasses in Indian kala-azar patient sera during disease, drug resistance, and cure. Acute-phase sera showed strong stimulation of IgG, followed by IgE and IgM and lastly by IgA antibodies. IgG subclass analysis revealed expression of all of the subclasses, with a predominance of IgG1 during disease. Following sodium stibogluconate (SAG) resistance, the levels of IgG, IgM, IgE, and IgG4 remained constant, while there was a decrease in the titers of IgG2 and IgG3. In contrast, a significant (2.2-fold) increase in IgG1 was observed in these individuals. Cure, in both SAG-responsive and unresponsive patients, correlated with a decline in the levels of IgG, IgM, IgE, and all of the IgG subclasses. The stimulation of IgG1 and the persistence, most importantly, of IgE and IgG4 following drug resistance, along with a decline in IgE, IgG4, and IgG1 with cure, demonstrate the potential of these isotypes as possible markers for monitoring effective treatment in kala-azar. PMID:10569788

Habitual intake of flavonoid subclasses and risk of colorectal cancer in 2 large prospective cohorts.

PubMed

Nimptsch, Katharina; Zhang, Xuehong; Cassidy, Aedín; Song, Mingyang; O'Reilly, Éilis J; Lin, Jennifer H; Pischon, Tobias; Rimm, Eric B; Willett, Walter C; Fuchs, Charles S; Ogino, Shuji; Chan, Andrew T; Giovannucci, Edward L; Wu, Kana

2016-01-01

Flavonoids inhibit the growth of colon cancer cells in vitro. In a secondary analysis of a randomized controlled trial, the Polyp Prevention Trial, a higher intake of one subclass, flavonols, was statistically significantly associated with a reduced risk of recurrent advanced adenoma. Most previous prospective studies on colorectal cancer evaluated only a limited number of flavonoid subclasses and intake ranges, yielding inconsistent results. In this study, we examined whether higher habitual dietary intakes of flavonoid subclasses (flavonols, flavones, flavanones, flavan-3-ols, and anthocyanins) were associated with a lower risk of colorectal cancer. Using data from validated food-frequency questionnaires administered every 4 y and an updated flavonoid food composition database, we calculated flavonoid intakes for 42,478 male participants from the Health Professionals Follow-Up Study and for 76,364 female participants from the Nurses' Health Study. During up to 26 y of follow-up, 2519 colorectal cancer cases (1061 in men, 1458 in women) were documented. Intakes of flavonoid subclasses were not associated with risk of colorectal cancer in either cohort. Pooled multivariable adjusted RRs (95% CIs) comparing the highest with the lowest quintiles were 1.04 (0.91, 1.18) for flavonols, 1.01 (0.89, 1.15) for flavones, 0.96 (0.84, 1.10) for flavanones, 1.07 (0.95, 1.21) for flavan-3-ols, and 0.98 (0.81, 1.19) for anthocyanins (all P values for heterogeneity by sex >0.19). In subsite analyses, flavonoid intake was also not associated with colon or rectal cancer risk. Our findings do not support the hypothesis that a higher habitual intake of any flavonoid subclass decreases the risk of colorectal cancer.

Specific DNA binding activity of T antigen subclasses varies among different SV40-transformed cell lines.

PubMed

Burger, C; Fanning, E

1983-04-15

Large tumor antigen (T antigen) occurs in at least three different oligomeric subclasses in cells infected or transformed by simian virus 40 (SV40): 5-7 S, 14-16 S, and 23-25 S. The 23-25 S form is complexed with a host phosphoprotein (p53). The DNA binding properties of these three subclasses of T antigen from nine different cell lines and free p53 protein were compared using an immunoprecipitation assay. All three subclasses of T antigen bound specifically to SV40 DNA sequences near the origin of replication. However, the DNA binding activity varied between different cell lines over a 40- to 50-fold range. The 23-25 S and 14-16 S forms from most of the cell lines tested bound much less SV40 origin DNA than 5-7 S T antigen. The free p53 phosphoprotein did not bind specifically to any SV40 DNA sequences.

Increased sensitivity and high specificity of indirect immunofluorescence in detecting IgG subclasses for diagnosis of bullous pemphigoid.

PubMed

Jankásková, J; Horváth, O N; Varga, R; Arenberger, P; Schmidt, E; Ruzicka, T; Sárdy, M

2018-04-01

Indirect immunofluorescence (IIF) microscopy on monkey oesophagus is an important assay for the diagnosis of bullous pemphigoid (BP). Its relatively low sensitivity (60-80%) may be partly due to insufficient detection of minor IgG subclasses. To determine the operating characteristics of an IgG subclass in IIF. We designed a retrospective, dual-centre, controlled cohort study on sera from 64 BP sera that had been rated as false negatives by traditional IIF microscopy, and assessed circulating IgG 1 , IgG 3 and IgG 4 autoantibodies. The sensitivities of IIF in detecting IgG 1 , IgG 3 , IgG 4 and all three in combination were 45.3%, 18.8%, 32.8% and 48.4%, respectively. Specificities were > 97%. Detection of IgG subclass (especially IgG 1 and IgG 4 ) autoantibodies by IIF on monkey oesophagus can significantly improve diagnostic performance of IIF microscopy for diagnosis of BP. © 2018 British Association of Dermatologists.

Testing the basic assumption of the hydrogeomorphic approach to assessing wetland functions.

PubMed

Hruby, T

2001-05-01

The hydrogeomorphic (HGM) approach for developing "rapid" wetland function assessment methods stipulates that the variables used are to be scaled based on data collected at sites judged to be the best at performing the wetland functions (reference standard sites). A critical step in the process is to choose the least altered wetlands in a hydrogeomorphic subclass to use as a reference standard against which other wetlands are compared. The basic assumption made in this approach is that wetlands judged to have had the least human impact have the highest level of sustainable performance for all functions. The levels at which functions are performed in these least altered wetlands are assumed to be "characteristic" for the subclass and "sustainable." Results from data collected in wetlands in the lowlands of western Washington suggest that the assumption may not be appropriate for this region. Teams developing methods for assessing wetland functions did not find that the least altered wetlands in a subclass had a range of performance levels that could be identified as "characteristic" or "sustainable." Forty-four wetlands in four hydrogeomorphic subclasses (two depressional subclasses and two riverine subclasses) were rated by teams of experts on the severity of their human alterations and on the level of performance of 15 wetland functions. An ordinal scale of 1-5 was used to quantify alterations in water regime, soils, vegetation, buffers, and contributing basin. Performance of functions was judged on an ordinal scale of 1-7. Relatively unaltered wetlands were judged to perform individual functions at levels that spanned all of the seven possible ratings in all four subclasses. The basic assumption of the HGM approach, that the least altered wetlands represent "characteristic" and "sustainable" levels of functioning that are different from those found in altered wetlands, was not confirmed. Although the intent of the HGM approach is to use level of functioning as a metric to assess the ecological integrity or "health" of the wetland ecosystem, the metric does not seem to work in western Washington for that purpose.

Thyroglobulin autoantibodies switch to immunoglobulin (Ig)G1 and IgG3 subclasses and preserve their restricted epitope pattern after 131I treatment for Graves' hyperthyroidism: the activity of autoimmune disease influences subclass distribution but not epitope pattern of autoantibodies

PubMed Central

Latrofa, F; Ricci, D; Montanelli, L; Piaggi, P; Mazzi, B; Bianchi, F; Brozzi, F; Santini, P; Fiore, E; Marinò, M; Tonacchera, M; Vitti, P

2014-01-01

The subclass distribution of thyroglobulin autoantibodies (TgAb) is debated, whereas their epitope pattern is restricted. Radioidine (131I) treatment for Graves' disease (GD) induces a rise in TgAb levels, but it is unknown whether it modifies subclass distribution and epitope pattern of TgAb as well. We collected sera from GD patients before 131I treatment and 3 and 6 months thereafter. We measured total TgAb, TgAb light chains and TgAb subclasses by enzyme-linked immunosorbent assay (ELISA) in 25 patients. We characterized the TgAb epitope pattern in 30 patients by inhibiting their binding to 125-ITg by a pool of four TgAb-Fab (recognizing Tg epitope regions A, B, C and D) and to Tg in ELISA by each TgAb-Fab. Total TgAb immunoglobulin (Ig)G rose significantly (P = 0·024). TgAb κ chains did not change (P = 0·052), whereas TgAb λ chains increased significantly (P = 0·001) and persistently. We observed a significant rise in IgG1 and IgG3 levels after 131I (P = 0·008 and P = 0·006, respectively), while IgG2 and IgG4 levels did not change. The rise of IgG1 was persistent, that of IgG3 transient. The levels of inhibition of TgAb binding to Tg by the TgAb-Fab pool were comparable. A slight, non-significant reduction of the inhibition by the immune-dominant TgAb-Fab A was observed 3 and 6 months after 131I. We conclude that 131I treatment for GD increases the levels of the complement-activating IgG1 and IgG3 subclasses and does not influence significantly the epitope pattern of TgAb. In autoimmune thyroid disease subclass distribution of autoantibodies is dynamic in spite of a stable epitope pattern. PMID:25134846

Two-stage neural-network-based technique for Urdu character two-dimensional shape representation, classification, and recognition

NASA Astrophysics Data System (ADS)

Megherbi, Dalila B.; Lodhi, S. M.; Boulenouar, A. J.

2001-03-01

This work is in the field of automated document processing. This work addresses the problem of representation and recognition of Urdu characters using Fourier representation and a Neural Network architecture. In particular, we show that a two-stage Neural Network scheme is used here to make classification of 36 Urdu characters into seven sub-classes namely subclasses characterized by seven proposed and defined fuzzy features specifically related to Urdu characters. We show that here Fourier Descriptors and Neural Network provide a remarkably simple way to draw definite conclusions from vague, ambiguous, noisy or imprecise information. In particular, we illustrate the concept of interest regions and describe a framing method that provides a way to make the proposed technique for Urdu characters recognition robust and invariant to scaling and translation. We also show that a given character rotation is dealt with by using the Hotelling transform. This transform is based upon the eigenvalue decomposition of the covariance matrix of an image, providing a method of determining the orientation of the major axis of an object within an image. Finally experimental results are presented to show the power and robustness of the proposed two-stage Neural Network based technique for Urdu character recognition, its fault tolerance, and high recognition accuracy.

Deciding the liveness for a subclass of weighted Petri nets based on structurally circular wait

NASA Astrophysics Data System (ADS)

Liu, GuanJun; Chen, LiJing

2016-05-01

Weighted Petri nets as a kind of formal language are widely used to model and verify discrete event systems related to resource allocation like flexible manufacturing systems. System of Simple Sequential Processes with Multi-Resources (S3PMR, a subclass of weighted Petri nets and an important extension to the well-known System of Simple Sequential Processes with Resources, can model many discrete event systems in which (1) multiple processes may run in parallel and (2) each execution step of each process may use multiple units from multiple resource types. This paper gives a necessary and sufficient condition for the liveness of S3PMR. A new structural concept called Structurally Circular Wait (SCW) is proposed for S3PMR. Blocking Marking (BM) associated with an SCW is defined. It is proven that a marked S3PMR is live if and only if each SCW has no BM. We use an example of multi-processor system-on-chip to show that SCW and BM can precisely characterise the (partial) deadlocks for S3PMR. Simultaneously, two examples are used to show the advantages of SCW in preventing deadlocks of S3PMR. These results are significant for the further research on dealing with the deadlock problem.

Binding affinity of pro-apoptotic BH3 peptides for the anti-apoptotic Mcl-1 and A1 proteins: Molecular dynamics simulations of Mcl-1 and A1 in complex with six different BH3 peptides.

PubMed

Modi, Vivek; Sankararamakrishnan, Ramasubbu

2017-05-01

The anti-apoptotic members of Bcl-2 family of proteins bind to their pro-apoptotic counterparts to induce or prevent cell death.Based on the distinct binding profiles for specific pro-apoptotic BH3 peptides, the anti-apoptotic Bcl-2 proteins can be divided into at least two subclasses. The subclass that includes Bcl-X L binds strongly to Bad BH3 peptide while it has weak binding affinity for the second subclass of Bcl-2 proteins such as Mcl-1 and A1. Anti-apoptotic Bcl-2 proteins are considered to be attractive drug targets for anti-cancer drugs. BH3-mimetic inhibitors such as ABT-737 have been shown to be specific to Bcl-X L subclass while Mcl-1 and A1 show resistance to the same drug. An efficacious inhibitor should target all the anti-apoptotic Bcl-2 proteins. Hence, development of inhibitors selective to Mcl-1 and A1 is of prime importance for targeted cancer therapeutics. The first step to achieve this goal is to understand the molecular basis of high binding affinities of specific pro-apoptotic BH3 peptides for Mcl-1 and A1. To understand the interactions between the BH3 peptides and Mcl-1/A1, we performed multi-nanosecond molecular dynamics (MD) simulations of six complex structures of Mcl-1 and A1. With the exception of Bad, all complex structures were experimentally determined. Bad complex structures were modeled. Our simulation studies identified specific pattern of polar interactions between Mcl-1/A1 and high-affinity binding BH3 peptides. The lack of such polar interactions in Bad peptide complex is attributed to specific basic residues present before and after the highly conserved Leu residue. The close approach of basic residues in Bad and Mcl-1/A1 is hypothesized to be the cause of weak binding affinity. To test this hypothesis, we generated in silico mutants of these basic residues in Bad peptide and Mcl-1/A1 proteins. MD simulations of the mutant systems established the pattern of stable polar interactions observed in high-affinity binding BH3 peptides. We have thus identified specific residue positions in Bad and Mcl-1/A1 responsible for the weak binding affinity. Results from these simulation studies will aid in the development of inhibitors specific to Mcl-1 and A1 proteins. Copyright © 2017 Elsevier Inc. All rights reserved.

Functional Differentiation of SWI/SNF Remodelers in Transcription and Cell Cycle Control▿ †

PubMed Central

Moshkin, Yuri M.; Mohrmann, Lisette; van Ijcken, Wilfred F. J.; Verrijzer, C. Peter

2007-01-01

Drosophila BAP and PBAP represent two evolutionarily conserved subclasses of SWI/SNF chromatin remodelers. The two complexes share the same core subunits, including the BRM ATPase, but differ in a few signature subunits: OSA defines BAP, whereas Polybromo (PB) and BAP170 specify PBAP. Here, we present a comprehensive structure-function analysis of BAP and PBAP. An RNA interference knockdown survey revealed that the core subunits BRM and MOR are critical for the structural integrity of both complexes. Whole-genome expression profiling suggested that the SWI/SNF core complex is largely dysfunctional in cells. Regulation of the majority of target genes required the signature subunit OSA, PB, or BAP170, suggesting that SWI/SNF remodelers function mostly as holoenzymes. BAP and PBAP execute similar, independent, or antagonistic functions in transcription control and appear to direct mostly distinct biological processes. BAP, but not PBAP, is required for cell cycle progression through mitosis. Because in yeast the PBAP-homologous complex, RSC, controls cell cycle progression, our finding reveals a functional switch during evolution. BAP mediates G2/M transition through direct regulation of string/cdc25. Its signature subunit, OSA, is required for directing BAP to the string/cdc25 promoter. Our results suggest that the core subunits play architectural and enzymatic roles but that the signature subunits determine most of the functional specificity of SWI/SNF holoenzymes in general gene control. PMID:17101803

Global Mapping of Traditional Chinese Medicine into Bioactivity Space and Pathways Annotation Improves Mechanistic Understanding and Discovers Relationships between Therapeutic Action (Sub)classes

PubMed Central

Mohamad Zobir, Siti Zuraidah; Mohd Fauzi, Fazlin; Liggi, Sonia; Drakakis, Georgios; Fu, Xianjun; Fan, Tai-Ping; Bender, Andreas

2016-01-01

Traditional Chinese medicine (TCM) still needs more scientific rationale to be proven for it to be accepted further in the West. We are now in the position to propose computational hypotheses for the mode-of-actions (MOAs) of 45 TCM therapeutic action (sub)classes from in silico target prediction algorithms, whose target was later annotated with Kyoto Encyclopedia of Genes and Genomes pathway, and to discover the relationship between them by generating a hierarchical clustering. The results of 10,749 TCM compounds showed 183 enriched targets and 99 enriched pathways from Estimation Score ≤ 0 and ≥ 5% of compounds/targets in a (sub)class. The MOA of a (sub)class was established from supporting literature. Overall, the most frequent top three enriched targets/pathways were immune-related targets such as tyrosine-protein phosphatase nonreceptor type 2 (PTPN2) and digestive system such as mineral absorption. We found two major protein families, G-protein coupled receptor (GPCR), and protein kinase family contributed to the diversity of the bioactivity space, while digestive system was consistently annotated pathway motif, which agreed with the important treatment principle of TCM, “the foundation of acquired constitution” that includes spleen and stomach. In short, the TCM (sub)classes, in many cases share similar targets/pathways despite having different indications. PMID:26989424

Large scale aggregate microarray analysis reveals three distinct molecular subclasses of human preeclampsia.

PubMed

Leavey, Katherine; Bainbridge, Shannon A; Cox, Brian J

2015-01-01

Preeclampsia (PE) is a life-threatening hypertensive pathology of pregnancy affecting 3-5% of all pregnancies. To date, PE has no cure, early detection markers, or effective treatments short of the removal of what is thought to be the causative organ, the placenta, which may necessitate a preterm delivery. Additionally, numerous small placental microarray studies attempting to identify "PE-specific" genes have yielded inconsistent results. We therefore hypothesize that preeclampsia is a multifactorial disease encompassing several pathology subclasses, and that large cohort placental gene expression analysis will reveal these groups. To address our hypothesis, we utilized known bioinformatic methods to aggregate 7 microarray data sets across multiple platforms in order to generate a large data set of 173 patient samples, including 77 with preeclampsia. Unsupervised clustering of these patient samples revealed three distinct molecular subclasses of PE. This included a "canonical" PE subclass demonstrating elevated expression of known PE markers and genes associated with poor oxygenation and increased secretion, as well as two other subclasses potentially representing a poor maternal response to pregnancy and an immunological presentation of preeclampsia. Our analysis sheds new light on the heterogeneity of PE patients, and offers up additional avenues for future investigation. Hopefully, our subclassification of preeclampsia based on molecular diversity will finally lead to the development of robust diagnostics and patient-based treatments for this disorder.

Prostate extracellular vesicles in patient plasma as a liquid biopsy platform for prostate cancer using nanoscale flow cytometry.

PubMed

Biggs, Colleen N; Siddiqui, Khurram M; Al-Zahrani, Ali A; Pardhan, Siddika; Brett, Sabine I; Guo, Qiu Q; Yang, Jun; Wolf, Philipp; Power, Nicholas E; Durfee, Paul N; MacMillan, Connor D; Townson, Jason L; Brinker, Jeffrey C; Fleshner, Neil E; Izawa, Jonathan I; Chambers, Ann F; Chin, Joseph L; Leong, Hon S

2016-02-23

Extracellular vesicles released by prostate cancer present in seminal fluid, urine, and blood may represent a non-invasive means to identify and prioritize patients with intermediate risk and high risk of prostate cancer. We hypothesize that enumeration of circulating prostate microparticles (PMPs), a type of extracellular vesicle (EV), can identify patients with Gleason Score≥4+4 prostate cancer (PCa) in a manner independent of PSA. Plasmas from healthy volunteers, benign prostatic hyperplasia patients, and PCa patients with various Gleason score patterns were analyzed for PMPs. We used nanoscale flow cytometry to enumerate PMPs which were defined as submicron events (100-1000nm) immunoreactive to anti-PSMA mAb when compared to isotype control labeled samples. Levels of PMPs (counts/µL of plasma) were also compared to CellSearch CTC Subclasses in various PCa metastatic disease subtypes (treatment naïve, castration resistant prostate cancer) and in serially collected plasma sets from patients undergoing radical prostatectomy. PMP levels in plasma as enumerated by nanoscale flow cytometry are effective in distinguishing PCa patients with Gleason Score≥8 disease, a high-risk prognostic factor, from patients with Gleason Score≤7 PCa, which carries an intermediate risk of PCa recurrence. PMP levels were independent of PSA and significantly decreased after surgical resection of the prostate, demonstrating its prognostic potential for clinical follow-up. CTC subclasses did not decrease after prostatectomy and were not effective in distinguishing localized PCa patients from metastatic PCa patients. PMP enumeration was able to identify patients with Gleason Score ≥8 PCa but not patients with Gleason Score 4+3 PCa, but offers greater confidence than CTC counts in identifying patients with metastatic prostate cancer. CTC Subclass analysis was also not effective for post-prostatectomy follow up and for distinguishing metastatic PCa and localized PCa patients. Nanoscale flow cytometry of PMPs presents an emerging biomarker platform for various stages of prostate cancer.

Prostate extracellular vesicles in patient plasma as a liquid biopsy platform for prostate cancer using nanoscale flow cytometry

PubMed Central

Al-Zahrani, Ali A.; Pardhan, Siddika; Brett, Sabine I.; Guo, Qiu Q.; Yang, Jun; Wolf, Philipp; Power, Nicholas E.; Durfee, Paul N.; MacMillan, Connor D.; Townson, Jason L.; Brinker, Jeffrey C.; Fleshner, Neil E.; Izawa, Jonathan I.; Chambers, Ann F.; Chin, Joseph L.; Leong, Hon S.

2016-01-01

Background Extracellular vesicles released by prostate cancer present in seminal fluid, urine, and blood may represent a non-invasive means to identify and prioritize patients with intermediate risk and high risk of prostate cancer. We hypothesize that enumeration of circulating prostate microparticles (PMPs), a type of extracellular vesicle (EV), can identify patients with Gleason Score≥4+4 prostate cancer (PCa) in a manner independent of PSA. Patients and Methods Plasmas from healthy volunteers, benign prostatic hyperplasia patients, and PCa patients with various Gleason score patterns were analyzed for PMPs. We used nanoscale flow cytometry to enumerate PMPs which were defined as submicron events (100-1000nm) immunoreactive to anti-PSMA mAb when compared to isotype control labeled samples. Levels of PMPs (counts/μL of plasma) were also compared to CellSearch CTC Subclasses in various PCa metastatic disease subtypes (treatment naïve, castration resistant prostate cancer) and in serially collected plasma sets from patients undergoing radical prostatectomy. Results PMP levels in plasma as enumerated by nanoscale flow cytometry are effective in distinguishing PCa patients with Gleason Score≥8 disease, a high-risk prognostic factor, from patients with Gleason Score≤7 PCa, which carries an intermediate risk of PCa recurrence. PMP levels were independent of PSA and significantly decreased after surgical resection of the prostate, demonstrating its prognostic potential for clinical follow-up. CTC subclasses did not decrease after prostatectomy and were not effective in distinguishing localized PCa patients from metastatic PCa patients. Conclusions PMP enumeration was able to identify patients with Gleason Score ≥8 PCa but not patients with Gleason Score 4+3 PCa, but offers greater confidence than CTC counts in identifying patients with metastatic prostate cancer. CTC Subclass analysis was also not effective for post-prostatectomy follow up and for distinguishing metastatic PCa and localized PCa patients. Nanoscale flow cytometry of PMPs presents an emerging biomarker platform for various stages of prostate cancer. PMID:26814433

Exact analytical modeling of lightwave propagation in planar media with arbitrarily graded index profiles

NASA Astrophysics Data System (ADS)

Krapez, J.-C.

2018-02-01

Applying the Darboux transformation in the optical-depth space allows building infinite chains of exact analytical solutions of the electromagnetic (EM) fields in planar 1D-graded dielectrics. As a matter of fact, infinite chains of solvable admittance profiles (e.g. refractive-index profiles, in the case of non-magnetic materials), together with the related EM fields are simultaneously and recursively obtained. The whole procedure has received the name "PROFIDT method" for PROperty and FIeld Darboux Transformation method. By repeating the Darboux transformations we can find out progressively more complex profiles and their EM solutions. An alternative is to stop after the first step and settle for a particular class of four-parameter admittance profiles that were dubbed of "sech(ξ)-type". These profiles are highly flexible. For this reason, they can be used as elementary bricks for building and modeling profiles of arbitrary shape. In addition, the corresponding transfer matrix involves only elementary functions. The sub-class of "sech(ξ)-type" profiles with horizontal end-slopes (S-shaped function) is particularly interesting: these can be used for high-level modeling of piecewise-sigmoidal refractive-index profiles encountered in various photonic devices such as matchinglayers, antireflection layers, rugate filters, chirped mirrors and photonic crystals. These simple analytical tools also allow exploring the fascinating properties of a new kind of structure, namely smooth quasicrystals. They can also be applied to model propagation of other types of waves in graded media such as acoustic waves and electric waves in tapered transmission lines.

Lipoprotein Subfractions in Metabolic Syndrome and Obesity: Clinical Significance and Therapeutic Approaches

PubMed Central

Nikolic, Dragana; Katsiki, Niki; Montalto, Giuseppe; Isenovic, Esma R.; Mikhailidis, Dimitri P.; Rizzo, Manfredi

2013-01-01

Small, dense low density lipoprotein (sdLDL) represents an emerging cardiovascular risk factor, since these particles can be associated with cardiovascular disease (CVD) independently of established risk factors, including plasma lipids. Obese subjects frequently have atherogenic dyslipidaemia, including elevated sdLDL levels, in addition to elevated triglycerides (TG), very low density lipoprotein (VLDL) and apolipoprotein-B, as well as decreased high density lipoprotein cholesterol (HDL-C) levels. Obesity-related co-morbidities, such as metabolic syndrome (MetS) are also characterized by dyslipidaemia. Therefore, agents that favourably modulate LDL subclasses may be of clinical value in these subjects. Statins are the lipid-lowering drug of choice. Also, anti-obesity and lipid lowering drugs other than statins could be useful in these patients. However, the effects of anti-obesity drugs on CVD risk factors remain unclear. We review the clinical significance of sdLDL in being overweight and obesity, as well as the efficacy of anti-obesity drugs on LDL subfractions in these individuals; a short comment on HDL subclasses is also included. Our literature search was based on PubMed and Scopus listings. Further research is required to fully explore both the significance of sdLDL and the efficacy of anti-obesity drugs on LDL subfractions in being overweight, obesity and MetS. Improving the lipoprotein profile in these patients may represent an efficient approach for reducing cardiovascular risk. PMID:23507795

New wideband radar target classification method based on neural learning and modified Euclidean metric

NASA Astrophysics Data System (ADS)

Jiang, Yicheng; Cheng, Ping; Ou, Yangkui

2001-09-01

A new method for target classification of high-range resolution radar is proposed. It tries to use neural learning to obtain invariant subclass features of training range profiles. A modified Euclidean metric based on the Box-Cox transformation technique is investigated for Nearest Neighbor target classification improvement. The classification experiments using real radar data of three different aircraft have demonstrated that classification error can reduce 8% if this method proposed in this paper is chosen instead of the conventional method. The results of this paper have shown that by choosing an optimized metric, it is indeed possible to reduce the classification error without increasing the number of samples.

Antibody-Mediated Internalization of Infectious HIV-1 Virions Differs among Antibody Isotypes and Subclasses.

PubMed

Tay, Matthew Zirui; Liu, Pinghuang; Williams, LaTonya D; McRaven, Michael D; Sawant, Sheetal; Gurley, Thaddeus C; Xu, Thomas T; Dennison, S Moses; Liao, Hua-Xin; Chenine, Agnès-Laurence; Alam, S Munir; Moody, M Anthony; Hope, Thomas J; Haynes, Barton F; Tomaras, Georgia D

2016-08-01

Emerging data support a role for antibody Fc-mediated antiviral activity in vaccine efficacy and in the control of HIV-1 replication by broadly neutralizing antibodies. Antibody-mediated virus internalization is an Fc-mediated function that may act at the portal of entry whereby effector cells may be triggered by pre-existing antibodies to prevent HIV-1 acquisition. Understanding the capacity of HIV-1 antibodies in mediating internalization of HIV-1 virions by primary monocytes is critical to understanding their full antiviral potency. Antibody isotypes/subclasses differ in functional profile, with consequences for their antiviral activity. For instance, in the RV144 vaccine trial that achieved partial efficacy, Env IgA correlated with increased risk of HIV-1 infection (i.e. decreased vaccine efficacy), whereas V1-V2 IgG3 correlated with decreased risk of HIV-1 infection (i.e. increased vaccine efficacy). Thus, understanding the different functional attributes of HIV-1 specific IgG1, IgG3 and IgA antibodies will help define the mechanisms of immune protection. Here, we utilized an in vitro flow cytometric method utilizing primary monocytes as phagocytes and infectious HIV-1 virions as targets to determine the capacity of Env IgA (IgA1, IgA2), IgG1 and IgG3 antibodies to mediate HIV-1 infectious virion internalization. Importantly, both broadly neutralizing antibodies (i.e. PG9, 2G12, CH31, VRC01 IgG) and non-broadly neutralizing antibodies (i.e. 7B2 mAb, mucosal HIV-1+ IgG) mediated internalization of HIV-1 virions. Furthermore, we found that Env IgG3 of multiple specificities (i.e. CD4bs, V1-V2 and gp41) mediated increased infectious virion internalization over Env IgG1 of the same specificity, while Env IgA mediated decreased infectious virion internalization compared to IgG1. These data demonstrate that antibody-mediated internalization of HIV-1 virions depends on antibody specificity and isotype. Evaluation of the phagocytic potency of vaccine-induced antibodies and therapeutic antibodies will enable a better understanding of their capacity to prevent and/or control HIV-1 infection in vivo.

Antibody-Mediated Internalization of Infectious HIV-1 Virions Differs among Antibody Isotypes and Subclasses

PubMed Central

McRaven, Michael D; Sawant, Sheetal; Gurley, Thaddeus C; Xu, Thomas T.; Dennison, S. Moses; Liao, Hua-Xin; Chenine, Agnès-Laurence; Alam, S. Munir; Haynes, Barton F.; Tomaras, Georgia D.

2016-01-01

Emerging data support a role for antibody Fc-mediated antiviral activity in vaccine efficacy and in the control of HIV-1 replication by broadly neutralizing antibodies. Antibody-mediated virus internalization is an Fc-mediated function that may act at the portal of entry whereby effector cells may be triggered by pre-existing antibodies to prevent HIV-1 acquisition. Understanding the capacity of HIV-1 antibodies in mediating internalization of HIV-1 virions by primary monocytes is critical to understanding their full antiviral potency. Antibody isotypes/subclasses differ in functional profile, with consequences for their antiviral activity. For instance, in the RV144 vaccine trial that achieved partial efficacy, Env IgA correlated with increased risk of HIV-1 infection (i.e. decreased vaccine efficacy), whereas V1-V2 IgG3 correlated with decreased risk of HIV-1 infection (i.e. increased vaccine efficacy). Thus, understanding the different functional attributes of HIV-1 specific IgG1, IgG3 and IgA antibodies will help define the mechanisms of immune protection. Here, we utilized an in vitro flow cytometric method utilizing primary monocytes as phagocytes and infectious HIV-1 virions as targets to determine the capacity of Env IgA (IgA1, IgA2), IgG1 and IgG3 antibodies to mediate HIV-1 infectious virion internalization. Importantly, both broadly neutralizing antibodies (i.e. PG9, 2G12, CH31, VRC01 IgG) and non-broadly neutralizing antibodies (i.e. 7B2 mAb, mucosal HIV-1+ IgG) mediated internalization of HIV-1 virions. Furthermore, we found that Env IgG3 of multiple specificities (i.e. CD4bs, V1-V2 and gp41) mediated increased infectious virion internalization over Env IgG1 of the same specificity, while Env IgA mediated decreased infectious virion internalization compared to IgG1. These data demonstrate that antibody-mediated internalization of HIV-1 virions depends on antibody specificity and isotype. Evaluation of the phagocytic potency of vaccine-induced antibodies and therapeutic antibodies will enable a better understanding of their capacity to prevent and/or control HIV-1 infection in vivo. PMID:27579713

IgG subclass alterations in adult asthma.

PubMed

Outschoorn, I M; Natta, C L

1992-01-01

Immunoglobulin levels were measured in serum samples of 12 black adult non-smoking asthmatic patients, 11 females and 1 male, and compared with 15 age-, sex-matched normal controls. Their total IgG, IgA and IgM levels were within the normal range. However, on quantitation of subclasses, IgG1 levels were significantly above normal, while IgG2 and IgG3 levels were significantly lower than those of controls. No significant differences were found between the two groups when IgG4 levels were compared. These studies as well as those of others suggest that immunoglobulin administration, particularly of individual subclasses, might prove to be a beneficial addition in the management of this condition.

Serodiagnosis of parasitic diseases.

PubMed Central

Maddison, S E

1991-01-01

In this review on serodiagnosis of parasitic diseases, antibody detection, antigen detection, use of monoclonal antibodies in parasitic serodiagnosis, molecular biological technology, and skin tests are discussed. The focus at the Centers for Disease Control on developing improved antigens, a truly quantitative FAST-enzyme-linked immunosorbent assay, and the very specific immunoblot assays for antibody detection is highlighted. The last two assays are suitable for field studies. Identification of patient response in terms of immunoglobulin class or immunoglobulin G subclass isotypes or both is discussed. Immunoglobulin isotypes may asist in defining the stage of some diseases. In other instances, use of a particular anti-isotype conjugate may increase the specificity of the assay. Monoclonal antibodies have played important roles in antigen purification and identification, in competitive antibody assays with increased sensitivity and specificity, and in assays for antigen detection in serum, body fluids, or excreta. Molecular biological technology has allowed significant advances in the production of defined parasitic serodiagnostic antigens. PMID:1747862

Limits of Generalization between Categories and Implications for Theories of Category Specificity

PubMed Central

Bukach, Cindy M.; Phillips, W. Stewart; Gauthier, Isabel

2010-01-01

Both domain-specific and expertise accounts of category specialization assume that generalization occurs within a domain but not between domains. Yet it is often difficult to define the boundaries and critical features of object domains. Differences in how categories are defined make it difficult to adjudicate between accounts of category specificity and may lead to contradictory results. For example, evidence for whether car experts recruit the fusiform face area is mixed and this inconsistency may be due to the inclusion of antique cars in one of the studies. The current study tested the generalization of expertise from modern to antique cars and found that modern car experts showed expert discrimination and holistic processing of modern cars, but not antique cars. These findings suggest that the neural specialization underlying perceptual expertise is highly specific and may not generalize to distinct subclasses, even when they share some degree of perceptual and conceptual features. PMID:20952784

Object-oriented analysis and design of a health care management information system.

PubMed

Krol, M; Reich, D L

1999-04-01

We have created a prototype for a universal object-oriented model of a health care system compatible with the object-oriented approach used in version 3.0 of the HL7 standard for communication messages. A set of three models has been developed: (1) the Object Model describes the hierarchical structure of objects in a system--their identity, relationships, attributes, and operations; (2) the Dynamic Model represents the sequence of operations in time as a collection of state diagrams for object classes in the system; and (3) functional Diagram represents the transformation of data within a system by means of data flow diagrams. Within these models, we have defined major object classes of health care participants and their subclasses, associations, attributes and operators, states, and behavioral scenarios. We have also defined the major processes and subprocesses. The top-down design approach allows use, reuse, and cloning of standard components.

Sudan ebolavirus long recovered survivors produce GP-specific Abs that are of the IgG1 subclass and preferentially bind FcγRI.

PubMed

Radinsky, Olga; Edri, Avishay; Brusilovsky, Michael; Fedida-Metula, Shlomit; Sobarzo, Ariel; Gershoni-Yahalom, Orly; Lutwama, Julius; Dye, John; Lobel, Leslie; Porgador, Angel

2017-07-20

Ebolavirus is a highly lethal pathogen, causing a severe hemorrhagic disease with a high fatality rate. To better understand immune correlates of protection by virus specific IgG, we investigated the evolution of the Fcγ receptors (FcγRs)-activating capabilities of antiviral IgG in serum samples of long recovered survivors. To this end, longitudinal serum samples from survivors of Sudan ebolavirus (SUDV) infection, studied over years, were examined for the presence of Ebola-GP specific IgG subclasses, and for their binding to FcγRs. We developed a cell-based reporter system to quantitate pathogen-specific antibody binding to FcγRIIIA, FcγRIIA, FcγRIIB and FcγRI. With this system, we demonstrate that anti-GP-specific stimulation of the FcγRI reporter by survivors' sera was substantially high one year after acute infection, with a slight reduction in activity over a decade post infection. We further demonstrate that GP-specific IgG1 is by far the seroprevalent subclass that retained and even enhanced its presence in the sera, over ten years post infection; the prevalence of other GP-specific IgG subclasses was considerably reduced over time. In accordance, GP-specific FcγRI reporter response and GP-specific total IgG1 subclass correlated in the studied group of Ebola survivors. These observations are important for further informing Ebola vaccine and therapeutic development.

Bovine IgG subclasses and fertility of Echinococcus granulosus hydatid cysts.

PubMed

Riesle, Silke; García, María Pía; Hidalgo, Christian; Galanti, Norbel; Saenz, Leonardo; Paredes, Rodolfo

2014-09-15

Hydatidosis is an important zoonotic disease of worldwide distribution, causing important health problems to humans and major economical losses in infected livestock. Echinococcus granulosus, the etiological agent of hydatid disease, induces a humoral immune response in the intermediate host (human and herbivorous) against hydatid cyst antigens. Specifically, IgGs are found in the laminar and germinal layers and inside the lumen of fertile and infertile hydatid cysts. In the germinal layer of infertile cysts IgGs are found in an order of magnitude greater than in the germinal layer of fertile cysts; a fraction of those IgGs are associated with high affinity to germinal layer proteins, suggesting their binding to specific parasite antigens. We have previously shown that those immunoglobulins, bound with high affinity to the germinal layer of hydatid cysts, induce apoptosis leading to cyst infertility. In the present work the presence of IgG1 and IgG2 subclasses in the germinal layer of both fertile and infertile hydatid cysts is reported. IgG1 is the most relevant immunoglobulin subclass present in the germinal layer of infertile cysts and bound with high affinity to that parasite structure. Contrarily, though the IgG2 subclass was also found in the germinal and adventitial layers, those immunoglobulins show low affinity to parasite antigens. We propose that the binding of an IgG1 subclass to parasite antigens present in the germinal layer is involved in the mechanism of cyst infertility. Copyright © 2014 Elsevier B.V. All rights reserved.

A New Classification System for IgG4 Autoantibodies

PubMed Central

Koneczny, Inga

2018-01-01

IgG4 autoimmune diseases are characterized by the presence of antigen-specific autoantibodies of the IgG4 subclass and contain well-characterized diseases such as muscle-specific kinase myasthenia gravis, pemphigus, and thrombotic thrombocytopenic purpura. In recent years, several new diseases were identified, and by now 14 antigens targeted by IgG4 autoantibodies have been described. The IgG4 subclass is considered immunologically inert and functionally monovalent due to structural differences compared to other IgG subclasses. IgG4 usually arises after chronic exposure to antigen and competes with other antibody species, thus “blocking” their pathogenic effector mechanisms. Accordingly, in the context of IgG4 autoimmunity, the pathogenicity of IgG4 is associated with blocking of enzymatic activity or protein–protein interactions of the target antigen. Pathogenicity of IgG4 autoantibodies has not yet been systematically analyzed in IgG4 autoimmune diseases. Here, we establish a modified classification system based on Witebsky’s postulates to determine IgG4 pathogenicity in IgG4 autoimmune diseases, review characteristics and pathogenic mechanisms of IgG4 in these disorders, and also investigate the contribution of other antibody entities to pathophysiology by additional mechanisms. As a result, three classes of IgG4 autoimmune diseases emerge: class I where IgG4 pathogenicity is validated by the use of subclass-specific autoantibodies in animal models and/or in vitro models of pathogenicity; class II where IgG4 pathogenicity is highly suspected but lack validation by the use of subclass specific antibodies in in vitro models of pathogenicity or animal models; and class III with insufficient data or a pathogenic mechanism associated with multivalent antigen binding. Five out of the 14 IgG4 antigens were validated as class I, five as class II, and four as class III. Antibodies of other IgG subclasses or immunoglobulin classes were present in several diseases and could contribute additional pathogenic mechanisms. PMID:29483905

Effects of weak/non-complement-binding HLA antibodies on C1q-binding.

PubMed

Hönger, G; Amico, P; Arnold, M-L; Spriewald, B M; Schaub, S

2017-08-01

It is unknown under what conditions and to what extent weak/non-complement (C)-binding IgG subclasses (IgG2/IgG4) can block C1q-binding triggered by C-binding IgG subclasses (IgG1/IgG3). Therefore, we investigated in vitro C1q-binding induced by IgG subclass mixtures targeting the same HLA epitope. Various mixtures of HLA class II specific monoclonal antibodies of different IgG subclasses but identical V-region were incubated with HLA DRB1*07:01 beads and monitored for C1q-binding. The lowest concentration to achieve maximum C1q-binding was measured for IgG3, followed by IgG1, while IgG2 and IgG4 did not show appreciable C1q-binding. C1q-binding occurred only after a critical amount of IgG1/3 has bound and sharply increased thereafter. When both, C-binding and weak/non-C-binding IgG subclasses were mixed, C1q-binding was diminished proportionally to the fraction of IgG2/4. A 2- to 4-fold excess of IgG2/4 inhibited C1q-binding by 50%. Very high levels (10-fold excess) almost completely abrogated C1q-binding even in the presence of significant IgG1/3 levels that would usually lead to strong C1q-binding. In sensitized renal allograft recipients, IgG subclass constellations with ≥ 2-fold excess of IgG2/4 over IgG1/3 were present in 23/66 patients (34.8%) and overall revealed slightly decreased C1q signals. However, spiking of patient sera with IgG2 targeting a different epitope than the patient's IgG1/3 synergistically increased C1q-binding. In conclusion, if targeting the same epitope, an excess of IgG2/4 is repressing the extent of IgG1/3 triggered C1q-binding in vitro. Such IgG subclass constellations are present in about a third of sensitized patients and their net effect on C1q-binding is slightly inhibitory. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Toward Exosome-Based Therapeutics: Isolation, Heterogeneity, and Fit-for-Purpose Potency

PubMed Central

Willis, Gareth R.; Kourembanas, Stella; Mitsialis, S. Alex

2017-01-01

Exosomes are defined as submicron (30–150 nm), lipid bilayer-enclosed extracellular vesicles (EVs), specifically generated by the late endosomal compartment through fusion of multivesicular bodies with the plasma membrane. Produced by almost all cells, exosomes were originally considered to represent just a mechanism for jettisoning unwanted cellular moieties. Although this may be a major function in most cells, evolution has recruited the endosomal membrane-sorting pathway to duties beyond mere garbage disposal, one of the most notable examples being its cooption by retroviruses for the generation of Trojan virions. It is, therefore, tempting to speculate that certain cell types have evolved an exosome subclass active in intracellular communication. We term this EV subclass “signalosomes” and define them as exosomes that are produced by the “signaling” cells upon specific physiological or environmental cues and harbor cargo capable of modulating the programming of recipient cells. Our recent studies have established that signalosomes released by mesenchymal stem/stromal cells (MSCs) represent the main vector of MSC immunomodulation and therapeutic action in animal models of lung disease. The efficacy of MSC-exosome treatments in a number of preclinical models of cardiovascular and pulmonary disease supports the promise of application of exosome-based therapeutics across a wide range of pathologies within the near future. However, the full realization of exosome therapeutic potential has been hampered by the absence of standardization in EV isolation, and procedures for purification of signalosomes from the main exosome population. This is mainly due to immature methodologies for exosome isolation and characterization and our incomplete understanding of the specific characteristics and molecular composition of signalosomes. In addition, difficulties in defining metrics for potency of exosome preparations and the challenges of industrial scale-up and good manufacturing practice compliance have complicated smooth and timely transition to clinical development. In this manuscript, we focus on cell culture conditions, exosome harvesting, dosage, and exosome potency, providing some empirical guidance and perspectives on the challenges in bringing exosome-based therapies to clinic. PMID:29062835

The triglyceride to high-density lipoprotein-cholesterol ratio in adolescence and subsequent weight gain predict nuclear magnetic resonance-measured lipoprotein subclasses in adulthood.

PubMed

Weiss, Ram; Otvos, James D; Sinnreich, Ronit; Miserez, Andre R; Kark, Jeremy D

2011-01-01

To assess whether the fasting triglyceride-to-high-density lipoprotein (HDL)-cholesterol (TG/HDL) ratio in adolescence is predictive of a proatherogenic lipid profile in adulthood. A longitudinal follow-up of 770 Israeli adolescents 16 to 17 years of age who participated in the Jerusalem Lipid Research Clinic study and were reevaluated 13 years later. Lipoprotein particle size was assessed at the follow-up with proton nuclear magnetic resonance. The TG/HDL ratio measured in adolescence was strongly associated with low-density lipoprotein, very low-density lipoprotein (VLDL), and HDL mean particle size in young adulthood in both sexes, even after adjustment for baseline body mass index and body mass index change. The TG/HDL ratio measured in adolescence and subsequent weight gain independently predicted atherogenic small low-density lipoprotein and large VLDL particle concentrations (P < .001 in both sexes). Baseline TG/HDL and weight gain interacted to increase large VLDL concentration in men (P < .001). Adolescents with an elevated TG/HDL ratio are prone to express a proatherogenic lipid profile in adulthood. This profile is additionally worsened by weight gain. Copyright © 2011 Mosby, Inc. All rights reserved.

New perspectives on CKD-induced dyslipidemia.

PubMed

Bermúdez-López, Marcelino; Arroyo, David; Betriu, Àngels; Masana, Luis; Fernández, Elvira; Valdivielso, Jose M

2017-10-01

Chronic kidney disease (CKD) is a world-wide health concern associated with a significantly higher cardiovascular morbidity and mortality. One of the principal cardiovascular risk factors is the lipid profile. CKD patients have a more frequent and progressive atheromatous disease that cannot be explained by the classical lipid parameters used in the daily clinical practice. Areas covered: The current review summarizes prevailing knowledge on the role of lipids in atheromathosis in CKD patients, including an overview of lipoprotein metabolism highlighting the CKD-induced alterations. Moreover, to obtain information beyond traditional lipid parameters, new state-of-the-art technologies such as lipoprotein subfraction profiling and lipidomics are also reviewed. Finally, we analyse the potential of new lipoprotein subclasses as therapeutic targets in CKD. Expert opinion: The CKD-induced lipid profile has specific features distinct from the general population. Besides quantitative alterations, renal patients have a plethora of qualitative lipid alterations that cannot be detected by routine determinations and are responsible for the excess of cardiovascular risk. New parameters, such as lipoprotein particle number and size, together with new biomarkers obtained by lipidomics will personalize the management of these patients. Therefore, nephrologists need to be aware of new insights into lipoprotein metabolism to improve cardiovascular risk assessment.

Classification of Automated Search Traffic

NASA Astrophysics Data System (ADS)

Buehrer, Greg; Stokes, Jack W.; Chellapilla, Kumar; Platt, John C.

As web search providers seek to improve both relevance and response times, they are challenged by the ever-increasing tax of automated search query traffic. Third party systems interact with search engines for a variety of reasons, such as monitoring a web site’s rank, augmenting online games, or possibly to maliciously alter click-through rates. In this paper, we investigate automated traffic (sometimes referred to as bot traffic) in the query stream of a large search engine provider. We define automated traffic as any search query not generated by a human in real time. We first provide examples of different categories of query logs generated by automated means. We then develop many different features that distinguish between queries generated by people searching for information, and those generated by automated processes. We categorize these features into two classes, either an interpretation of the physical model of human interactions, or as behavioral patterns of automated interactions. Using the these detection features, we next classify the query stream using multiple binary classifiers. In addition, a multiclass classifier is then developed to identify subclasses of both normal and automated traffic. An active learning algorithm is used to suggest which user sessions to label to improve the accuracy of the multiclass classifier, while also seeking to discover new classes of automated traffic. Performance analysis are then provided. Finally, the multiclass classifier is used to predict the subclass distribution for the search query stream.

Palmprint and Face Multi-Modal Biometric Recognition Based on SDA-GSVD and Its Kernelization

PubMed Central

Jing, Xiao-Yuan; Li, Sheng; Li, Wen-Qian; Yao, Yong-Fang; Lan, Chao; Lu, Jia-Sen; Yang, Jing-Yu

2012-01-01

When extracting discriminative features from multimodal data, current methods rarely concern themselves with the data distribution. In this paper, we present an assumption that is consistent with the viewpoint of discrimination, that is, a person's overall biometric data should be regarded as one class in the input space, and his different biometric data can form different Gaussians distributions, i.e., different subclasses. Hence, we propose a novel multimodal feature extraction and recognition approach based on subclass discriminant analysis (SDA). Specifically, one person's different bio-data are treated as different subclasses of one class, and a transformed space is calculated, where the difference among subclasses belonging to different persons is maximized, and the difference within each subclass is minimized. Then, the obtained multimodal features are used for classification. Two solutions are presented to overcome the singularity problem encountered in calculation, which are using PCA preprocessing, and employing the generalized singular value decomposition (GSVD) technique, respectively. Further, we provide nonlinear extensions of SDA based multimodal feature extraction, that is, the feature fusion based on KPCA-SDA and KSDA-GSVD. In KPCA-SDA, we first apply Kernel PCA on each single modal before performing SDA. While in KSDA-GSVD, we directly perform Kernel SDA to fuse multimodal data by applying GSVD to avoid the singular problem. For simplicity two typical types of biometric data are considered in this paper, i.e., palmprint data and face data. Compared with several representative multimodal biometrics recognition methods, experimental results show that our approaches outperform related multimodal recognition methods and KSDA-GSVD achieves the best recognition performance. PMID:22778600

Absolute Quantitation of Glycoforms of Two Human IgG Subclasses Using Synthetic Fc Peptides and Glycopeptides

NASA Astrophysics Data System (ADS)

Roy, Rini; Ang, Evelyn; Komatsu, Emy; Domalaon, Ronald; Bosseboeuf, Adrien; Harb, Jean; Hermouet, Sylvie; Krokhin, Oleg; Schweizer, Frank; Perreault, Hélène

2018-05-01

Immunoglobulins, such as immunoglobulin G (IgG), are of prime importance in the immune system. Polyclonal human IgG comprises four subclasses, of which IgG1 and IgG2 are the most abundant in healthy individuals. In an effort to develop an absolute MALDI-ToF-MS quantitative method for these subclasses and their Fc N-glycoforms, (glyco)peptides were synthesized using a solid-phase approach and used as internal standards. Tryptic digest glycopeptides from monoclonal IgG1 and IgG2 samples were first quantified using EEQYN(GlcNAc)STYR and EEQFN(GlcNAc)STFR standards, respectively. For IgG1, a similar glycopeptide where tyrosine (Y) was isotopically labelled was used to quantify monoclonal IgG1 that had been treated with the enzyme Endo-F2, i.e., yielding tryptic glycopeptide EEQYN(GlcNAc)STYR. The next step was to quantify single subclasses within polyclonal human IgG samples. Although ion abundances in the MALDI spectra often showed higher signals for IgG2 than IgG1, depending on the spotting solvent used, determination of amounts using the newly developed quantitative method allowed to obtain accurate concentrations where IgG1 species were predominant. It was observed that simultaneous analysis of IgG1 and IgG2 yielded non-quantitative results and that more success was obtained when subclasses were quantified one by one. More experiments served to assess the respective extraction and ionization efficiencies of EEQYNSTYR/EEQFNSTFR and EEQYN(GlcNAc)STYR/EEQFN(GlcNAc)STFR mixtures under different solvent and concentration conditions.

Palmprint and face multi-modal biometric recognition based on SDA-GSVD and its kernelization.

PubMed

Jing, Xiao-Yuan; Li, Sheng; Li, Wen-Qian; Yao, Yong-Fang; Lan, Chao; Lu, Jia-Sen; Yang, Jing-Yu

2012-01-01

When extracting discriminative features from multimodal data, current methods rarely concern themselves with the data distribution. In this paper, we present an assumption that is consistent with the viewpoint of discrimination, that is, a person's overall biometric data should be regarded as one class in the input space, and his different biometric data can form different Gaussians distributions, i.e., different subclasses. Hence, we propose a novel multimodal feature extraction and recognition approach based on subclass discriminant analysis (SDA). Specifically, one person's different bio-data are treated as different subclasses of one class, and a transformed space is calculated, where the difference among subclasses belonging to different persons is maximized, and the difference within each subclass is minimized. Then, the obtained multimodal features are used for classification. Two solutions are presented to overcome the singularity problem encountered in calculation, which are using PCA preprocessing, and employing the generalized singular value decomposition (GSVD) technique, respectively. Further, we provide nonlinear extensions of SDA based multimodal feature extraction, that is, the feature fusion based on KPCA-SDA and KSDA-GSVD. In KPCA-SDA, we first apply Kernel PCA on each single modal before performing SDA. While in KSDA-GSVD, we directly perform Kernel SDA to fuse multimodal data by applying GSVD to avoid the singular problem. For simplicity two typical types of biometric data are considered in this paper, i.e., palmprint data and face data. Compared with several representative multimodal biometrics recognition methods, experimental results show that our approaches outperform related multimodal recognition methods and KSDA-GSVD achieves the best recognition performance.

The relative contributions of psychiatric symptoms and psychotropic medications on the sleep-wake profile of young persons with anxiety, depression and bipolar disorders.

PubMed

Robillard, Rébecca; Oxley, Cristal; Hermens, Daniel F; White, Django; Wallis, Ryan; Naismith, Sharon L; Whitwell, Bradley; Southan, James; Scott, Elizabeth M; Hickie, Ian B

2016-09-30

This study investigated the relative contribution of psychiatric symptoms and psychotropic medications on the sleep-wake cycle. Actigraphy and clinical assessments (Brief Psychiatric Rating Scale) were conducted in 146 youths with anxiety, depression or bipolar disorders. Independently of medications, mania symptoms were predictive of lower circadian amplitude and rhythmicity. Independently of diagnosis and symptoms severity: i) antipsychotics were related to longer sleep period and duration, ii) serotonin-norepinephrine reuptake inhibitors to longer sleep period, and iii) agomelatine to earlier sleep onset. Manic symptoms and different subclasses of medications may have independent influences on the sleep-wake cycle of young people with mental disorders. Copyright © 2016. Published by Elsevier Ireland Ltd.

Salivary IgG subclasses in individuals with and without homozygous IGHG gene deletions.

PubMed Central

Engström, P E; Norhagen, G; Osipova, L; Helal, A; Wiebe, V; Brusco, A; Carbonara, A O; Lefranc, G; Lefranc, M P

1996-01-01

In this study, the levels of salivary IgG1, IgG2, IgG3 and IgG4 from individuals with and without homozygous immunoglobulin heavy chain constant gene deletions were quantified by enzyme-linked immunosorbent assay (ELISA). To analyse the restriction of salivary IgG subclasses, we used unstimulated whole saliva and sera collected at the same time from individuals with homozygous gene deletions, two with G1 deletion, one with G4 deletion, six with both G2 and G4 deletions and from eight individuals without IGHG gene deletions and expressing all four IgG subclasses. The median values of salivary IgG from individuals with homozygous G1, or G4, or both G2 and G4 deletions, and from individuals expressing all four subclasses were 24.2 mg/l and 23.4 mg/l, respectively. The median values of serum IgG were 13.7 g/l and 15.9 g/l, respectively. Our results show that the salivary and serum IgG levels were both within the normal range in individuals with homozygous gene deletions of either G1, or G4, or both G2 and G4. PMID:8943711

Cap-shaped gastropods from Upper Jurassic and Lower Cretaceous deposits of northern East Siberia

NASA Astrophysics Data System (ADS)

Guzhov, A. V.; Zakharov, V. A.

2015-09-01

Cap-shaped gastropods are first identified in Upper Jurassic and Lower Cretaceous sections of northern East Siberia. They belong to three new genera of the subclass Pectinibranchia ( Boreioconus gen. nov., Nixepileolus gen. nov., and Taimyroconus gen. nov.), which are identified at the species level ( B. bojarkensis sp. nov., N. depressus sp. nov., T. zakharovi sp. nov.), and several species with the open nomenclature. The genus Taimyroconus attributed to the family Calyptraeidae is considered as an ancestral form of the genus Crepidula. The stratigraphic position of each taxon is determined for several sections. The facies confinement, habitat conditions, and ethology of defined genera are considered with the analysis of their geographic distribution.

[Human IgG subclass study. II. The levels of the individual IgG subclasses in paired sera from mothers and newborn infants as well as in the blood sera of inhabitants of an isolated northern village].

PubMed

Basova, E N; Stefani, D V; Kazantseva, L Z

1979-07-01

The levels of the first 3 subclasses of IgG, as determined by the radial immunodiffusion test, proved to be similar in the blood sera obtained from mothers and newborns in Moscow. The concentration of IgG4 was 0.64 +/- 0.02 g/l iently indicative of a limited passage of IgG4 molecules through the placenta. The inhabitants of an isolated northern village were found to have the inheritable combined deficit of IfG2 and IgG3 synthesis in their blood sera, which was probably due to the prolonged processes of inbreeding and the progenitor effect.

HIV-specific Fc effector function early in infection predicts the development of broadly neutralizing antibodies.

PubMed

Richardson, Simone I; Chung, Amy W; Natarajan, Harini; Mabvakure, Batsirai; Mkhize, Nonhlanhla N; Garrett, Nigel; Abdool Karim, Salim; Moore, Penny L; Ackerman, Margaret E; Alter, Galit; Morris, Lynn

2018-04-01

While the induction of broadly neutralizing antibodies (bNAbs) is a major goal of HIV vaccination strategies, there is mounting evidence to suggest that antibodies with Fc effector function also contribute to protection against HIV infection. Here we investigated Fc effector functionality of HIV-specific IgG plasma antibodies over 3 years of infection in 23 individuals, 13 of whom developed bNAbs. Antibody-dependent cellular phagocytosis (ADCP), complement deposition (ADCD), cellular cytotoxicity (ADCC) and cellular trogocytosis (ADCT) were detected in almost all individuals with levels of activity increasing over time. At 6 months post-infection, individuals with bNAbs had significantly higher levels of ADCD and ADCT that correlated with antibody binding to C1q and FcγRIIa respectively. In addition, antibodies from individuals with bNAbs showed more IgG subclass diversity to multiple HIV antigens which also correlated with Fc polyfunctionality. Germinal center activity represented by CXCL13 levels and expression of activation-induced cytidine deaminase (AID) was found to be associated with neutralization breadth, Fc polyfunctionality and IgG subclass diversity. Overall, multivariate analysis by random forest classification was able to group bNAb individuals with 85% sensitivity and 80% specificity based on the properties of their antibody Fc early in HIV infection. Thus, the Fc effector function profile predicted the development of neutralization breadth in this cohort, suggesting that intrinsic immune factors within the germinal center provide a mechanistic link between the Fc and Fab of HIV-specific antibodies.

HIV-specific Fc effector function early in infection predicts the development of broadly neutralizing antibodies

PubMed Central

Richardson, Simone I.; Mabvakure, Batsirai; Mkhize, Nonhlanhla N.; Moore, Penny L.; Alter, Galit

2018-01-01

While the induction of broadly neutralizing antibodies (bNAbs) is a major goal of HIV vaccination strategies, there is mounting evidence to suggest that antibodies with Fc effector function also contribute to protection against HIV infection. Here we investigated Fc effector functionality of HIV-specific IgG plasma antibodies over 3 years of infection in 23 individuals, 13 of whom developed bNAbs. Antibody-dependent cellular phagocytosis (ADCP), complement deposition (ADCD), cellular cytotoxicity (ADCC) and cellular trogocytosis (ADCT) were detected in almost all individuals with levels of activity increasing over time. At 6 months post-infection, individuals with bNAbs had significantly higher levels of ADCD and ADCT that correlated with antibody binding to C1q and FcγRIIa respectively. In addition, antibodies from individuals with bNAbs showed more IgG subclass diversity to multiple HIV antigens which also correlated with Fc polyfunctionality. Germinal center activity represented by CXCL13 levels and expression of activation-induced cytidine deaminase (AID) was found to be associated with neutralization breadth, Fc polyfunctionality and IgG subclass diversity. Overall, multivariate analysis by random forest classification was able to group bNAb individuals with 85% sensitivity and 80% specificity based on the properties of their antibody Fc early in HIV infection. Thus, the Fc effector function profile predicted the development of neutralization breadth in this cohort, suggesting that intrinsic immune factors within the germinal center provide a mechanistic link between the Fc and Fab of HIV-specific antibodies. PMID:29630668

Low density lipoprotein subclasses in Asian and Caucasian adolescent boys.

PubMed

Raschke, Verena; Elmadfa, Ibrahim; Bermingham, Margaret A; Steinbeck, Kate

2006-01-01

South Asian adults are known to have very high rates of Coronary heart disease (CHD) and insulin resistance and, even as adolescents, may show higher risk factors for CHD. The aim of this study was to investigate the prevalence of small, dense low density lipoprotein (sdLDL) subclasses in a cohort of adolescent boys. The specific objective was to investigate the relationship between measures of fatness, ethnicity and LDL diameter in this cohort. Preformed native (non-denaturing) polyacrylamide 3-13% gradient gels and a multipurpose vertical electrophoresis system were used for the separation of LDL sub-fractions in a single school year cohort of boys aged 15-16 years (n=135). Latex beads and thyroglobulin standards were used to construct a calibration curve in order to calculate LDL particle diameters by regression (Total Lab Software v1.11). ANOVA was used to compare LDL size among different ethnic groups (SPSS and Stat View). The study sample was comprised of 45.2% Caucasians, 41.5% East Asians and 13.3% from the Indian subcontinent (South Asians). There was a non-significant trend for South Asians to have a lower LDL diameter than either Caucasians or East Asian boys which was independent of % total body fat (%TBF) and body mass index (BMI). This is the first adolescent cohort to examine sdLDL which included Caucasians, East and South Asians. It appears that the higher risk profile for CHD and diabetes noted in South Asian adults may be evident even during adolescence.

Effect of dark, hard, and vitreous kernel content on protein molecular weight distribution and on milling and breadmaking quality characteristics for hard spring wheat samples from diverse growing regions

USDA-ARS?s Scientific Manuscript database

Kernel vitreousness is an important grading characteristic for segregation of sub-classes of hard red spring (HRS) wheat in the U.S. This research investigated the protein molecular weight distribution (MWD), and flour and baking quality characteristics of different HRS wheat market sub-classes. T...

Serum IgG subclass antibodies to a variety of food antigens in patients with coeliac disease.

PubMed Central

Hvatum, M; Scott, H; Brandtzaeg, P

1992-01-01

Levels of serum IgA, IgG, and IgG subclass antibodies to a variety of dietary antigens were determined by enzyme linked immunosorbent assays in 14 adults with untreated coeliac disease and in 10 disease controls selected because of raised total IgG activities. The untreated coeliacs showed somewhat higher total IgG activity (p approximately 0.05) and significantly raised IgA and IgG1 + IgG3 activities to gliadin but reduced IgG4 activity (p less than 0.02) compared with the controls. High IgA and IgG1 + IgG3 activities were positively correlated (r = 0.67, p less than 0.01), and so were IgG and IgG4 activities (r = 0.64, p less than 0.02). Conversely, a high IgG2 response to gliadin appeared related to a low IgA response (r = 0.55, p less than 0.05). The IgG2 response was most prominent to oat flour antigens, followed by IgG1; and the main response to soy antigens resided in IgG1, followed by IgG2 in both disease groups. There was no difference in antibody activities to oat and soy between the two groups, and raised activity to bovine serum albumin was seldom encountered. The IgA activity to alpha-lactalbumin and ovalbumin tended to be increased in the coeliacs compared with the controls. The IgG4 subclass dominated the IgG response to beta-lactoglobulin and ovalbumin and was often raised to alpha-lactalbumin, especially in the disease controls. The IgG subclass pattern to casein parallelled that to gliadin with dominance of the IgG1- and IgG3-subclass activities, especially in the coeliacs. The phlogistic potential of a response in these two subclasses might be relevant to the pathogenesis of coeliac disease and could contribute to a raised IgA gliadin response by increasing mucosal permeability. IgA activity seemed to be highest against antigens usually involved in IgE mediated food allergy. PMID:1612478

Bacterial community dynamics during start-up of a trickle-bed bioreactor degrading aromatic compounds.

PubMed

Stoffels, M; Amann, R; Ludwig, W; Hekmat, D; Schleifer, K H

1998-03-01

This study was performed with a laboratory-scale fixed-bed bioreactor degrading a mixture of aromatic compounds (Solvesso100). The starter culture for the bioreactor was prepared in a fermentor with a wastewater sample of a care painting facility as the inoculum and Solvesso100 as the sole carbon source. The bacterial community dynamics in the fermentor and the bioreactor were examined by a conventional isolation procedure and in situ hybridization with fluorescently labeled rRNA-targeted oligonucleotides. Two significant shifts in the bacterial community structure could be demonstrated. The original inoculum from the wastewater of the car factory was rich in proteobacteria of the alpha and beta subclasses, while the final fermentor enrichment was dominated by bacteria closely related to Pseudomonas putida or Pseudomonas mendocina, which both belong to the gamma subclass of the class Proteobacteria. A second significant shift was observed when the fermentor culture was transferred as inoculum to the trickle-bed bioreactor. The community structure in the bioreactor gradually returned to a higher complexity, with the dominance of beta and alpha subclass proteobacteria, whereas the gamma subclass proteobacteria sharply declined. Obviously, the preceded pollutant adaptant did not lead to a significant enrichment of bacteria that finally dominated in the trickle-bed bioreactor. In the course of experiments, three new 16S as well as 23S rRNA-targeted probes for beta subclass proteobacteria were designed, probe SUBU1237 for the genera Burkholderia and Sutterella, probe ALBO34a for the genera Alcaligenes and Bordetella, and probe Bcv13b for Burkholderia cepacia and Burkholderia vietnamiensis. Bacteria hybridizing with the probe Bcv13b represented the main Solvesso100-degrading population in the reactor.

Bacterial Community Dynamics during Start-Up of a Trickle-Bed Bioreactor Degrading Aromatic Compounds

PubMed Central

Stoffels, Marion; Amann, Rudolf; Ludwig, Wolfgang; Hekmat, Dariusch; Schleifer, Karl-Heinz

1998-01-01

This study was performed with a laboratory-scale fixed-bed bioreactor degrading a mixture of aromatic compounds (Solvesso100). The starter culture for the bioreactor was prepared in a fermentor with a wastewater sample of a car painting facility as the inoculum and Solvesso100 as the sole carbon source. The bacterial community dynamics in the fermentor and the bioreactor were examined by a conventional isolation procedure and in situ hybridization with fluorescently labeled rRNA-targeted oligonucleotides. Two significant shifts in the bacterial community structure could be demonstrated. The original inoculum from the wastewater of the car factory was rich in proteobacteria of the alpha and beta subclasses, while the final fermentor enrichment was dominated by bacteria closely related to Pseudomonas putida or Pseudomonas mendocina, which both belong to the gamma subclass of the class Proteobacteria. A second significant shift was observed when the fermentor culture was transferred as inoculum to the trickle-bed bioreactor. The community structure in the bioreactor gradually returned to a higher complexity, with the dominance of beta and alpha subclass proteobacteria, whereas the gamma subclass proteobacteria sharply declined. Obviously, the preceded pollutant adaptant did not lead to a significant enrichment of bacteria that finally dominated in the trickle-bed bioreactor. In the course of experiments, three new 16S as well as 23S rRNA-targeted probes for beta subclass proteobacteria were designed, probe SUBU1237 for the genera Burkholderia and Sutterella, probe ALBO34a for the genera Alcaligenes and Bordetella, and probe Bcv13b for Burkholderia cepacia and Burkholderia vietnamiensis. Bacteria hybridizing with the probe Bcv13b represented the main Solvesso100-degrading population in the reactor. PMID:9501433

Comparison of a reduced carbohydrate and reduced fat diet for LDL, HDL, and VLDL subclasses during 9-months of weight maintenance subsequent to weight loss.

PubMed

LeCheminant, James D; Smith, Bryan K; Westman, Eric C; Vernon, Mary C; Donnelly, Joseph E

2010-06-01

This study compared LDL, HDL, and VLDL subclasses in overweight or obese adults consuming either a reduced carbohydrate (RC) or reduced fat (RF) weight maintenance diet for 9 months following significant weight loss. Thirty-five (21 RC; 14 RF) overweight or obese middle-aged adults completed a 1-year weight management clinic. Participants met weekly for the first six months and bi-weekly thereafter. Meetings included instruction for diet, physical activity, and behavior change related to weight management. Additionally, participants followed a liquid very low-energy diet of approximately 2092 kJ per day for the first three months of the study. Subsequently, participants followed a dietary plan for nine months that targeted a reduced percentage of carbohydrate (approximately 20%) or fat (approximately 30%) intake and an energy intake level calculated to maintain weight loss. Lipid subclasses using NMR spectroscopy were analyzed prior to weight loss and at multiple intervals during weight maintenance. Body weight change was not significantly different within or between groups during weight maintenance (p>0.05). The RC group showed significant increases in mean LDL size, large LDL, total HDL, large and small HDL, mean VLDL size, and large VLDL during weight maintenance while the RF group showed increases in total HDL, large and small HDL, total VLDL, and large, medium, and small VLDL (p<0.05). Group*time interactions were significant for large and medium VLDL (p>0.05). Some individual lipid subclasses improved in both dietary groups. Large and medium VLDL subclasses increased to a greater extent across weight maintenance in the RF group.

Comparative functional expression of nAChR subtypes in rodent DRG neurons.

PubMed

Smith, Nathan J; Hone, Arik J; Memon, Tosifa; Bossi, Simon; Smith, Thomas E; McIntosh, J Michael; Olivera, Baldomero M; Teichert, Russell W

2013-01-01

We investigated the functional expression of nicotinic acetylcholine receptors (nAChRs) in heterogeneous populations of dissociated rat and mouse lumbar dorsal root ganglion (DRG) neurons by calcium imaging. By this experimental approach, it is possible to investigate the functional expression of multiple receptor and ion-channel subtypes across more than 100 neuronal and glial cells simultaneously. Based on nAChR expression, DRG neurons could be divided into four subclasses: (1) neurons that express predominantly α3β4 and α6β4 nAChRs; (2) neurons that express predominantly α7 nAChRs; (3) neurons that express a combination of α3β4/α6β4 and α7 nAChRs; and (4) neurons that do not express nAChRs. In this comparative study, the same four neuronal subclasses were observed in mouse and rat DRG. However, the expression frequency differed between species: substantially more rat DRG neurons were in the first three subclasses than mouse DRG neurons, at all developmental time points tested in our study. Approximately 70-80% of rat DRG neurons expressed functional nAChRs, in contrast to only ~15-30% of mouse DRG neurons. Our study also demonstrated functional coupling between nAChRs, voltage-gated calcium channels, and mitochondrial Ca(2) (+) transport in discrete subsets of DRG neurons. In contrast to the expression of nAChRs in DRG neurons, we demonstrated that a subset of non-neuronal DRG cells expressed muscarinic acetylcholine receptors and not nAChRs. The general approach to comparative cellular neurobiology outlined in this paper has the potential to better integrate molecular and systems neuroscience by uncovering the spectrum of neuronal subclasses present in a given cell population and the functionally integrated signaling components expressed in each subclass.

Association between ethnicity and obesity with high-density lipoprotein (HDL) function and subclass distribution.

PubMed

Woudberg, Nicholas J; Goedecke, Julia H; Blackhurst, Dee; Frias, Miguel; James, Richard; Opie, Lionel H; Lecour, Sandrine

2016-05-11

Obesity and low high-density lipoprotein-cholesterol (HDL-C) levels are associated with cardiovascular risk. Surprisingly, despite a greater prevalence of obesity and lower HDL concentrations than white women, black South African women are relatively protected against ischaemic heart disease. We investigated whether this apparent discrepancy may be related to different HDL function and subclass distribution in black and white, normal-weight and obese South African women (n = 40). HDL functionality was assessed by measuring paraoxonase (PON) activity, platelet activating factor acetylhydrolase (PAF-AH) activity, Oxygen Radical Absorbance Capacity (ORAC) and quantification of the expression of vascular cell adhesion molecule in endothelial cells. PON-1 and PAF-AH expression was determined in isolated HDL and serum using Western blotting. Levels of large, intermediate and small HDL subclasses were measured using the Lipoprint® system. PON activity was lower in white compared to black women (0.49 ± 0.09 U/L vs 0.78 ± 0.10 U/L, p < 0.05), regardless of PON-1 protein levels. Obese black women had lower PAF-AH activity (9.34 ± 1.15 U/L vs 13.89 ± 1.21 U/L, p <0.05) and HDL-associated PAF-AH expression compared to obese white women. Compared to normal-weight women, obese women had lower large HDL, greater intermediate and small HDL; an effect that was more pronounced in white women than black women. There were no differences in antioxidant capacity or anti-inflammatory function across groups. Our data show that both obesity and ethnicity are associated with differences in HDL functionality, while obesity was associated with decreases in large HDL subclass distribution. Measuring HDL functionality and subclass may, therefore, be important factors to consider when assessing cardiovascular risk.

Glycemic control and high-density lipoprotein characteristics in adolescents with type 1 diabetes.

PubMed

Medina-Bravo, Patricia; Medina-Urrutia, Aída; Juárez-Rojas, Juan Gabriel; Cardoso-Saldaña, Guillermo; Jorge-Galarza, Esteban; Posadas-Sánchez, Rosalinda; Coyote-Estrada, Ninel; Nishimura-Meguro, Elisa; Posadas-Romero, Carlos

2013-09-01

Recent evidence suggests that high-density lipoprotein (HDL) physicochemical characteristics and functional capacity may be more important that HDL-C levels in predicting coronary heart disease. There is little data regarding HDL subclasses distribution in youth with type 1 diabetes. To assess the relationships between glycemic control and HDL subclasses distribution, composition, and function in adolescents with type 1 diabetes. This cross-sectional study included 52 adolescents with type 1 diabetes aged 12-16 years and 43 age-matched non-diabetic controls. Patients were divided into two groups: one in fair control [hemoglobin A1c (HbA1c) < 9.6%] and the second group with poor glycemic control (HbA1c ≥ 9.6%). In all participants, we determined HDL subclasses distribution, composition, and the ability of plasma and of isolated HDL to promote cellular cholesterol efflux. Levels of soluble adhesion molecules were also measured. Although both groups of patients and the control group had similar HDL-C levels, linear regression analyses showed that compared with non-diabetic subjects, the poor control group had a lower proportion of HDL2b subclass (p = 0.029), triglyceride enriched (p = 0.045), and cholesteryl ester depleted (p = 0.028) HDL particles. Despite these HDL changes, cholesterol efflux was comparable among the three groups. The poor control group also had significantly higher intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 plasma concentrations. In adolescents with type 1 diabetes, poor glycemic control is associated with abnormalities in HDL subclasses distribution and HDL lipid composition, however, in spite of these HDL changes, the ability of HDL to promote cholesterol efflux remains comparable to that of healthy subjects. © 2012 John Wiley & Sons A/S.

Complement deposition induced by binding of anti-contactin-1 auto-antibodies is modified by immunoglobulins.

PubMed

Appeltshauser, Luise; Weishaupt, Andreas; Sommer, Claudia; Doppler, Kathrin

2017-01-01

Inflammatory neuropathies associated with auto-antibodies against paranodal proteins like contactin-1 are reported to respond poorly to treatment with intravenous immunoglobulins (IVIG). A reason might be that IVIG interacts with the complement pathway and these auto-antibodies often belong to the IgG4 subclass that does not activate complement. However, some patients do show a response to IVIG, especially at the beginning of the disease. This corresponds with the finding of coexisting IgG subclasses IgG1, IgG2 and IgG3. We therefore aimed to investigate complement deposition and activation by samples of three patients with anti-contactin-1 IgG auto-antibodies of different subclasses as a potential predictor for response to IVIG. Complement deposition and activation was measured by cell binding and ELISA based assays, and the effect of IVIG on complement deposition was assessed by addition of different concentrations of IVIG. Binding of anti-contactin-1 auto-antibodies of all three patients induced complement deposition and activation with the strongest effect shown by the serum of a patient with predominance of IgG3 auto-antibodies. IVIG led to a reduction of complement deposition in a dose-dependent manner, but did not reduce binding of auto-antibodies to contactin-1. We conclude that complement deposition may contribute to the pathophysiology of anti-contactin-1 associated neuropathy, particularly in patients with predominance of the IgG3 subclass. The proportion of different auto-antibody subclasses may be a predictor for the response to IVIG in patients with auto-antibodies against paranodal proteins. Copyright © 2016 Elsevier Inc. All rights reserved.

[EFFICACY OF IVIG TREATMENT IN BRONCHIECTASIS ASSOCIATED WITH IGG SUBCLASS DEFICIENCY].

PubMed

Shostak, Yael; Kramer, Mordechai R

2017-11-01

Bronchiectasis is characterized by an abnormal dilatation of the bronchi leading to a chronic inflammatory process, airway blockage and impaired clearance of secretions. The damage to the airways is usually progressive and is the result of several pathogenic processes. In the past, healing of infections (especially pulmonary tuberculosis) was the main cause of airway dilatation and progression of chronic inflammation. Today, congenital illnesses, anatomical defects and immune deficiency play an important role in the pathogenesis of bronchiectasis formation. The immunoglobulin repertoire is vital for effective host protection against a wide variety of pathogens. Primary antibody deficiency diseases are defects of the humoral arm of the immune system and involve an absence/reduced levels of one or more immunoglobulin classes/subclasses or defects of specific antibody formation. Immunoglobulin G (IGG) subclass deficiency can occur in a healthy person and could be without clinical significance. However, in recent years there is emerging evidence that in patients with recurrent infections, early diagnosis of antibody deficiency affects the prognosis and prevention of ongoing lung damage. The use of IVIG has contributed significantly to the survival rate in primary antibody deficiencies. There is limited literature on the treatment of IVIG for patients with IGG subclass deficiency. However, all studies presented so far demonstrated that immunoglobulin therapy reduced the rate of bacterial infections, days of antibiotic usage, hospital admissions and significantly increased patients' quality of life. Therefore, in the appropriate clinical setting, ie: a patient with bronchiectasis and recurrent infections, it is justified to test whether there are humoral immune defects such as IGG subclass deficiency. In a patient with proven deficiency, we should recommend to start IVIG treatment until clinical benefit is achieved.

Metabolic characterization of isocitrate dehydrogenase (IDH) mutant and IDH wildtype gliomaspheres uncovers cell type-specific vulnerabilities.

PubMed

Garrett, Matthew; Sperry, Jantzen; Braas, Daniel; Yan, Weihong; Le, Thuc M; Mottahedeh, Jack; Ludwig, Kirsten; Eskin, Ascia; Qin, Yue; Levy, Rachelle; Breunig, Joshua J; Pajonk, Frank; Graeber, Thomas G; Radu, Caius G; Christofk, Heather; Prins, Robert M; Lai, Albert; Liau, Linda M; Coppola, Giovanni; Kornblum, Harley I

2018-01-01

There is considerable interest in defining the metabolic abnormalities of IDH mutant tumors to exploit for therapy. While most studies have attempted to discern function by using cell lines transduced with exogenous IDH mutant enzyme, in this study, we perform unbiased metabolomics to discover metabolic differences between a cohort of patient-derived IDH1 mutant and IDH wildtype gliomaspheres. Using both our own microarray and the TCGA datasets, we performed KEGG analysis to define pathways differentially enriched in IDH1 mutant and IDH wildtype cells and tumors. Liquid chromatography coupled to mass spectrometry analysis with labeled glucose and deoxycytidine tracers was used to determine differences in overall cellular metabolism and nucleotide synthesis. Radiation-induced DNA damage and repair capacity was assessed using a comet assay. Differences between endogenous IDH1 mutant metabolism and that of IDH wildtype cells transduced with the IDH1 (R132H) mutation were also investigated. Our KEGG analysis revealed that IDH wildtype cells were enriched for pathways involved in de novo nucleotide synthesis, while IDH1 mutant cells were enriched for pathways involved in DNA repair. LC-MS analysis with fully labeled 13 C-glucose revealed distinct labeling patterns between IDH1 mutant and wildtype cells. Additional LC-MS tracing experiments confirmed increased de novo nucleotide synthesis in IDH wildtype cells relative to IDH1 mutant cells. Endogenous IDH1 mutant cultures incurred less DNA damage than IDH wildtype cultures and sustained better overall growth following X-ray radiation. Overexpression of mutant IDH1 in a wildtype line did not reproduce the range of metabolic differences observed in lines expressing endogenous mutations, but resulted in depletion of glutamine and TCA cycle intermediates, an increase in DNA damage following radiation, and a rise in intracellular ROS. These results demonstrate that IDH1 mutant and IDH wildtype cells are easily distinguishable metabolically by analyzing expression profiles and glucose consumption. Our results also highlight important differences in nucleotide synthesis utilization and DNA repair capacity that could be exploited for therapy. Altogether, this study demonstrates that IDH1 mutant gliomas are a distinct subclass of glioma with a less malignant, but also therapy-resistant, metabolic profile that will likely require distinct modes of therapy.

On certain subclasses of multivalent functions associated with an extended fractional differintegral operator

NASA Astrophysics Data System (ADS)

Patel, J.; Mishra, A. K.

2007-08-01

In the present paper an extended fractional differintegral operator , suitable for the study of multivalent functions is introduced. Various mapping properties and inclusion relationships between certain subclasses of multivalent functions are investigated by applying the techniques of differential subordination. Relevant connections of the definitions and results presented in this paper with those obtained in several earlier works on the subject are also pointed out.

Some distinguishing characteristics of contour and texture phenomena in images

NASA Technical Reports Server (NTRS)

Jobson, Daniel J.

1992-01-01

The development of generalized contour/texture discrimination techniques is a central element necessary for machine vision recognition and interpretation of arbitrary images. Here, the visual perception of texture, selected studies of texture analysis in machine vision, and diverse small samples of contour and texture are all used to provide insights into the fundamental characteristics of contour and texture. From these, an experimental discrimination scheme is developed and tested on a battery of natural images. The visual perception of texture defined fine texture as a subclass which is interpreted as shading and is distinct from coarse figural similarity textures. Also, perception defined the smallest scale for contour/texture discrimination as eight to nine visual acuity units. Three contour/texture discrimination parameters were found to be moderately successful for this scale discrimination: (1) lightness change in a blurred version of the image, (2) change in lightness change in the original image, and (3) percent change in edge counts relative to local maximum.

News from the proton - recent DIS results from HERA

DOE Office of Scientific and Technical Information (OSTI.GOV)

Meier, K.

1997-01-01

Recent results from the two large general-purpose detectors H1 and ZEUS at HERA (DESY, Hamburg, Germany) are presented. Emphasis is given to the analysis of deep inelastic scattering defined by the observation of the scattered electron or positron in the main calorimeters. Results on purely inclusive cross sections lead to a determination of the charged (quarks) parton distribution F{sub 2}(x, Q{sup 2}). Access to the electrically neutral parton content (gluons) is obtained indirectly by an analysis of the expected scaling violation behavior of F{sub 2} or directly from multijet rates originating from well-defined initial parton configurations. Finally, the recently uncoveredmore » subclass of large rapidity gap (LRG) events has been analyzed in terms of F{sub 2}. The result supports the concept of a color neutral object (Pomeron IP) being probed by a hard scattering electron. Evidence for factorization of the Pomeron radiation process as well as for scaling in the inclusive IP structure functions has been found.« less

[Distribution of IgG subclasses of TgAb and TPOAb in sera from patients with Graves' disease, Graves' disease plus Hashimoto's thyroiditis and Hashimoto's thyrotoxicosis].

PubMed

Yuan, Shanshan; Yu, Nan; Gao, Ying; Huang, Wei; He, Yifan; Dong, Bin; Lu, Guizhi; Li, Maorong; Cai, Xiaopin; Peng, Dingqiong; Wang, Yunhong; Li, Ting; Huang, Youyuan; Gao, Yanming; Guo, Xiaohui; Shi, Bingyin

2014-01-14

To evaluate the distribution of IgG subclasses of TgAb and TPOAb in sera from patients with Graves' disease (GD), Graves' disease plus Hashimoto's thyroiditis (GH) and Hashimoto's thyrotoxicosis. Patients with GD (n = 33), GH (n = 31) or Hashimoto's thyrotoxicosis (n = 18) diagnosed by fine needle aspiration cytology at Department of Endocrinology of Peking University First Hospital, Beijing Haidian Hospital, China-Japan Friendship Hospital and Civil Aviation General Hospital during the period from January 2010 to May 2013 were enrolled. All of them had TgAb and TPOAb. The total serum IgG and IgG subclasses of TgAb and TPOAb were detected by antigen-specific enzyme-linked immunosorbent assay (ELISA). The prevalence and relative amount of IgG subclasses were calculated and compared among three groups. The levels of TRAb in GD group (21.80(7.53, 40) U/L) were significantly higher than those in GH (7.30(3.10, 25.40) U/L) (P = 0.000) and Hashimoto's thyrotoxicosis groups (4.90(1.69, 16.43) U/L) (P = 0.003). And no significant differences were found in the levels of TgAb and TPOAb. The prevalence of TgAb IgG3 subclass in Hashimoto's thyrotoxicosis group (66.7%) was higher than GD group (35.5%) and GH group (36.4%) and the difference was close to significance (P = 0.066). There were significant differences of relative amount of TgAb IgG2 and TgAb IgG4 among three groups (P = 0.039 and 0.013), and GD patients had higher relative amounts of TgAb IgG2 (0.59(0.34, 0.94)) and TgAb IgG4 (0.57(0.28, 0.97)) than GH patients (TgAb IgG2, 0.31(0.23, 0.34); TgAb IgG4, 0.26(0.09, 0.48)) or patients with Hashimoto's thyrotoxicosis (TgAb IgG2, 0.32(0.24, 0.83); TgAb IgG4, 0.33(0.10, 0.65)) (for TgAb IgG2, P = 0.009 and 0.167; for TgAb IgG4, P = 0.005 and 0.041 respectively). No significant difference was found in the prevalence of each TPOAb IgG subclass. The difference of relative amount of TPOAb IgG2 among three groups was close to significance (P = 0.069). And the relative amount was higher in sera from GD patients (0.39 ± 0.04) than that in GH patients (0.29 ± 0.13) or patients with Hashimoto's thyrotoxicosis (0.26 ± 0.02) (P = 0.104 and 0.002 respectively). The patients with high levels of TgAb IgG2, TgAb IgG4 and TPOAb IgG2 subclasses have a greater risk of GD. The IgG subclass distribution of TgAb and TPOAb might help to differentiate the causes of thyrotoxicosis in autoimmune thyroid diseases.

LDL electronegativity index: a potential novel index for predicting cardiovascular disease.

PubMed

Ivanova, Ekaterina A; Bobryshev, Yuri V; Orekhov, Alexander N

2015-01-01

High cardiovascular risk conditions are frequently associated with altered plasma lipoprotein profile, such as elevated low-density lipoprotein (LDL) and LDL cholesterol and decreased high-density lipoprotein. There is, however, accumulating evidence that specific subclasses of LDL may play an important role in cardiovascular disease development, and their relative concentration can be regarded as a more relevant risk factor. LDL particles undergo multiple modifications in plasma that can lead to the increase of their negative charge. The resulting electronegative LDL [LDL(-)] subfraction has been demonstrated to be especially atherogenic, and became a subject of numerous recent studies. In this review, we discuss the physicochemical properties of LDL(-), methods of its detection, atherogenic activity, and relevance of the LDL electronegativity index as a potential independent predictor of cardiovascular risk.

LDL electronegativity index: a potential novel index for predicting cardiovascular disease

PubMed Central

Ivanova, Ekaterina A; Bobryshev, Yuri V; Orekhov, Alexander N

2015-01-01

High cardiovascular risk conditions are frequently associated with altered plasma lipoprotein profile, such as elevated low-density lipoprotein (LDL) and LDL cholesterol and decreased high-density lipoprotein. There is, however, accumulating evidence that specific subclasses of LDL may play an important role in cardiovascular disease development, and their relative concentration can be regarded as a more relevant risk factor. LDL particles undergo multiple modifications in plasma that can lead to the increase of their negative charge. The resulting electronegative LDL [LDL(–)] subfraction has been demonstrated to be especially atherogenic, and became a subject of numerous recent studies. In this review, we discuss the physicochemical properties of LDL(–), methods of its detection, atherogenic activity, and relevance of the LDL electronegativity index as a potential independent predictor of cardiovascular risk. PMID:26357481

(Epi)genotype–phenotype correlations in Beckwith–Wiedemann syndrome

PubMed Central

Mussa, Alessandro; Russo, Silvia; De Crescenzo, Agostina; Freschi, Andrea; Calzari, Luciano; Maitz, Silvia; Macchiaiolo, Marina; Molinatto, Cristina; Baldassarre, Giuseppina; Mariani, Milena; Tarani, Luigi; Bedeschi, Maria Francesca; Milani, Donatella; Melis, Daniela; Bartuli, Andrea; Cubellis, Maria Vittoria; Selicorni, Angelo; Cirillo Silengo, Margherita; Larizza, Lidia; Riccio, Andrea; Ferrero, Giovanni Battista

2016-01-01

Beckwith–Wiedemann syndrome (BWS) is characterized by cancer predisposition, overgrowth and highly variable association of macroglossia, abdominal wall defects, nephrourological anomalies, nevus flammeus, ear malformations, hypoglycemia, hemihyperplasia, and organomegaly. BWS molecular defects, causing alteration of expression or activity of the genes regulated by two imprinting centres (IC) in the 11p15 chromosomal region, are also heterogeneous. In this paper we define (epi)genotype–phenotype correlations in molecularly confirmed BWS patients. The characteristics of 318 BWS patients with proven molecular defect were compared among the main four molecular subclasses: IC2 loss of methylation (IC2-LoM, n=190), IC1 gain of methylation (IC1-GoM, n=31), chromosome 11p15 paternal uniparental disomy (UPD, n=87), and cyclin-dependent kinase inhibitor 1C gene (CDKN1C) variants (n=10). A characteristic growth pattern was found in each group; neonatal macrosomia was almost constant in IC1-GoM, postnatal overgrowth in IC2-LoM, and hemihyperplasia more common in UPD (P<0.001). Exomphalos was more common in IC2/CDKN1C patients (P<0.001). Renal defects were typical of UPD/IC1 patients, uretheral malformations of IC1-GoM cases (P<0.001). Ear anomalies and nevus flammeus were associated with IC2/CDKN1C genotype (P<0.001). Macroglossia was less common among UPD patients (P<0.001). Wilms' tumor was associated with IC1-GoM or UPD and never observed in IC2-LoM patients (P<0.001). Hepatoblastoma occurred only in UPD cases. Cancer risk was lower in IC2/CDKN1C, intermediate in UPD, and very high in IC1 cases (P=0.009). In conclusion, (epi)genotype–phenotype correlations define four different phenotypic BWS profiles with some degree of clinical overlap. These observations impact clinical care allowing to move toward (epi) genotype-based follow-up and cancer screening. PMID:25898929

Influence of formulation and processing on absorption and metabolism of flavan-3-ols from tea and cocoa.

PubMed

Neilson, Andrew P; Ferruzzi, Mario G

2011-01-01

Flavan-3-ols are a major subclass of the class of plant phytochemicals known as flavonoids. Flavan-3-ols are commonly found in fruit, vegetable, and botanical products, including tea, cocoa, grapes, and apples. Both monomeric catechins and polymeric procyanidins are common in the diet, along with several derivatives produced by degradation of these species during processing. Both epidemiological and biological evidence suggests a health-protective role for dietary flavan-3-ols, leading to increased interest in the bioavailability of these compounds from foods. Flavan-3-ol bioavailability depends on numerous factors, including digestive release, absorption, metabolism, and elimination. In addition to these in vivo factors, the complexity of whole-food systems (physical form, flavan-3-ol form and dose, macronutrient and micronutrient profile, processing, etc.) influences the absorption efficiency and circulating profile of flavan-3-ols. An understanding of how food matrices may influence flavan-3-ol absorption will provide a framework to design and develop functional products that positively affect flavan-3-ol absorption and, by extension, potential bioactivity.

Optical/Infrared properties of Be stars in X-ray Binary systems

NASA Astrophysics Data System (ADS)

Naik, Sachindra

2018-04-01

Be/X-ray binaries, consisting of a Be star and a compact object (neutron star), form the largest subclass of High Mass X-ray Binaries. The orbit of the compact object around the Be star is wide and highly eccentric. Neutron stars in the Be/X-ray binaries are generally quiescent in X-ray emission. Transient X-ray outbursts seen in these objects are thought to be due to the interaction between the compact object and the circumstellar disk of the Be star at the periastron passage. Optical/infrared observations of the companion Be star during these outbursts show that the increase in the X-ray intensity of the neutron star is coupled with the decrease in the optical/infrared flux of the companion star. Apart from the change in optical/infrared flux, dramatic changes in the Be star emission line profiles are also seen during X-ray outbursts. Observational evidences of changes in the emission line profiles and optical/infrared continuum flux along with associated X-ray outbursts from the neutron stars in several Be/X-ray binaries are presented in this paper.

Regulation of low-density lipoprotein subfractions by carbohydrates.

PubMed

Gerber, Philipp A; Berneis, Kaspar

2012-07-01

This article aims at reviewing the recent findings that have been made concerning the crosstalk of carbohydrate metabolism with the generation of small, dense low-density lipoprotein (LDL) particles, which are known to be associated with an adverse cardiovascular risk profile. Studies conducted during the past few years have quite unanimously shown that the quantity of carbohydrates ingested is associated with a decrease of LDL particle size and an increase in its density. Conversely, diets that aim at a reduction of carbohydrate intake are able to improve LDL quality. Furthermore, a reduction of the glycaemic index without changing the amount of carbohydrates ingested has similar effects. Diseases with altered carbohydrate metabolism, for example, type 2 diabetes, are associated with small, dense LDL particles. Finally, even the kind of monosaccharide the carbohydrate intake consists of is important concerning LDL particle size: fructose has been shown to alter the LDL particle subclass profile more adversely than glucose in many recent studies. LDL particle quality, rather than its quantity, is affected by carbohydrate metabolism, which is of clinical importance, in particular, in the light of increased carbohydrate consumption in today's world.

Genome-wide expression profiling in pediatric septic shock

PubMed Central

Wong, Hector R.

2013-01-01

For nearly a decade, our research group has had the privilege of developing and mining a multi-center, microarray-based, genome-wide expression database of critically ill children (≤ 10 years of age) with septic shock. Using bioinformatic and systems biology approaches, the expression data generated through this discovery-oriented, exploratory approach have been leveraged for a variety of objectives, which will be reviewed. Fundamental observations include wide spread repression of gene programs corresponding to the adaptive immune system, and biologically significant differential patterns of gene expression across developmental age groups. The data have also identified gene expression-based subclasses of pediatric septic shock having clinically relevant phenotypic differences. The data have also been leveraged for the discovery of novel therapeutic targets, and for the discovery and development of novel stratification and diagnostic biomarkers. Almost a decade of genome-wide expression profiling in pediatric septic shock is now demonstrating tangible results. The studies have progressed from an initial discovery-oriented and exploratory phase, to a new phase where the data are being translated and applied to address several areas of clinical need. PMID:23329198

Genomic analysis of diffuse pediatric low-grade gliomas identifies recurrent oncogenic truncating rearrangements in the transcription factor MYBL1

PubMed Central

Ramkissoon, Lori A.; Horowitz, Peleg M.; Craig, Justin M.; Ramkissoon, Shakti H.; Rich, Benjamin E.; Schumacher, Steven E.; McKenna, Aaron; Lawrence, Michael S.; Bergthold, Guillaume; Brastianos, Priscilla K.; Tabak, Barbara; Ducar, Matthew D.; Van Hummelen, Paul; MacConaill, Laura E.; Pouissant-Young, Tina; Cho, Yoon-Jae; Taha, Hala; Mahmoud, Madeha; Bowers, Daniel C.; Margraf, Linda; Tabori, Uri; Hawkins, Cynthia; Packer, Roger J.; Hill, D. Ashley; Pomeroy, Scott L.; Eberhart, Charles G.; Dunn, Ian F.; Goumnerova, Liliana; Getz, Gad; Chan, Jennifer A.; Santagata, Sandro; Hahn, William C.; Stiles, Charles D.; Ligon, Azra H.; Kieran, Mark W.; Beroukhim, Rameen; Ligon, Keith L.

2013-01-01

Pediatric low-grade gliomas (PLGGs) are among the most common solid tumors in children but, apart from BRAF kinase mutations or duplications in specific subclasses, few genetic driver events are known. Diffuse PLGGs comprise a set of uncommon subtypes that exhibit invasive growth and are therefore especially challenging clinically. We performed high-resolution copy-number analysis on 44 formalin-fixed, paraffin-embedded diffuse PLGGs to identify recurrent alterations. Diffuse PLGGs exhibited fewer such alterations than adult low-grade gliomas, but we identified several significantly recurrent events. The most significant event, 8q13.1 gain, was observed in 28% of diffuse astrocytoma grade IIs and resulted in partial duplication of the transcription factor MYBL1 with truncation of its C-terminal negative-regulatory domain. A similar recurrent deletion-truncation breakpoint was identified in two angiocentric gliomas in the related gene v-myb avian myeloblastosis viral oncogene homolog (MYB) on 6q23.3. Whole-genome sequencing of a MYBL1-rearranged diffuse astrocytoma grade II demonstrated MYBL1 tandem duplication and few other events. Truncated MYBL1 transcripts identified in this tumor induced anchorage-independent growth in 3T3 cells and tumor formation in nude mice. Truncated transcripts were also expressed in two additional tumors with MYBL1 partial duplication. Our results define clinically relevant molecular subclasses of diffuse PLGGs and highlight a potential role for the MYB family in the biology of low-grade gliomas. PMID:23633565

The somatic POLE P286R mutation defines a unique subclass of colorectal cancer featuring hypermutation, representing a potential genomic biomarker for immunotherapy

PubMed Central

Kim, Jihun; Kim, Deokhoon; Chun, Sung-Min; Kim, Jiyun; Kim, Tae Won; Park, Inja; Yu, Chang-Sik; Jang, Se Jin

2016-01-01

Early-onset colorectal cancers (EOCRCs) may have biological or genomic features distinct from late-onset CRCs (LOCRCs). Previous studies have mostly focused on the germline predisposition conditions of EOCRCs, but we hypothesized that EOCRCs may have distinct somatic aberrations that accelerate cancer development. To identify the somatic aberrations that accelerate cancer development at an early age, we conducted whole exome sequencing for 28 polyposis-unrelated, microsatellite stable (MSS) EOCRCs with no known germline predisposition conditions. Surprisingly, we found two distinct groups in the context of mutational burden: 6 hypermutated cases with 2325 to 10973 mutations and 22 nonhypermutated cases with 47 to 154 mutations. Further analysis revealed that four of the six hypermutated cases had the same POLE P286R mutation. We validated this finding in 83 MSS EOCRCs and 27 MSS LOCRCs, which revealed that 7.2% of EOCRCs (6/83) had the POLE P286R mutation, which was not found in LOCRCs. Clinicopathologically, EOCRCs with POLE mutations occurred far more frequently in the right colon than in the left colon, affecting men more frequently than women. In summary, we have identified a unique subclass of colon cancer characterized by a hypermutation associated with the POLE mutation. The acquisition of the POLE mutation leading to hypermutation can accelerate cancer development. Clinically, this subset with hypermutation may be susceptible to immune checkpoint blockade. PMID:27612425

The Incredibly Long-Lived SN 2005ip

NASA Astrophysics Data System (ADS)

Fox, Ori

2016-10-01

Type IIn supernovae (SNe IIn) are defined by their relatively narrow spectral line features associated with a dense circumstellar medium (CSM) formed by the progenitor star. The nature of the progenitor and mass loss remains relatively unknown. Shock interaction with the dense CSM can often result in significant UV emission for several years post-explosion, thereby probing the CSM characteristics, progenitor mass loss history and, ultimately, the progenitor itself. The Type IIn SN 2005ip proves to be one of the most interesting and well-studied targets within this subclass. Compared to all other supernovae, SN 2005ip is the most luminous for its age. Now more than 11 years post-explosion, the SN has released >10^51 erg throughout its lifetime as the forward shock continues to collide with a dense CSM. Here we propose HST/STIS-MAMA UV observations of SN 2005ip to investigate the massive CSM. When accounting for the shock travel time, these observations will probe material lost from the progenitor more than 1000 years prior to the explosion. We already have a single HST/STIS spectrum of SN 2005ip from 2014, which was obtained while the shock was still within a higher mass regime. With just 5 orbits, a second spectrum will allow us to directly trace the evolution of the CSM and produce new constraints on the pre-SN mass-loss history. Coinciding with Cycle 24's UV Initiative, this program offers new insight regarding both the progenitor and explosion characteristics of the SN IIn subclass.

IGG Subclass and Isotype Specific Immunoglobulin Responses to Lassa Fever and Venezuelan Equine Encephalomyelitis: Natural Infection and Immunization

DTIC Science & Technology

1991-12-30

AD-A246 912 AD ARMY PROJECT ORDER 88PP8804 TITLE: IGG SUBCLASS AND ISOTYPE SPECIFIC IMMUNOGLOBULIN RESPONSES TO LASSA FEVER AND VENEZUELAN EQUINE ...and Isotype Specific Immunoglobulin responses Army Project Order to Lassa Fever and Venezuelan Equine Encephalitis: 88PP8804 Natual...unlimited 13. ABSTRACT (Maximum 200 words) Venezuelan Equine Encephalitis (VEE) specific inimunoglobulin responses to the two vaccines, TC-83 (A live

IgG2 deficiency in sickle cell anaemia.

PubMed

Natta, C L; Outschoorn, I M

1984-08-01

8 patients with known sickle cell anaemia were studied immunologically. The concentrations of the main immunoglobulin classes, IgG and IgA, were significantly higher than the levels in 11 normal age- and sex-matched black subjects (P less than 0.01). IgM levels were not significantly different in the two groups. There was a heterogeneity in the interaction of the IgG subclasses with Protein A, with low levels of IgG2. The IgG2:IgG1 ratios varied from 1:3.8 to 1:6 (normals 1:3). In 4 patients the absolute levels of IgG2 as measured by radial immunodiffusion were lower than normal, thus confirming the chromatographic ratios. Since specific antibody is often restricted to a single subclass, the levels of IgG subclasses may be related to recurrent bacterial infections in these patients.

Immunoglobulin patterns in humans over 95 years of age.

PubMed Central

Radl, J; Sepers, J M; Skvaril, F; Morell, A; Hijmans, W

1975-01-01

Immunoglobulin patterns were investigated in seventy-three volunteers older than 95 years. An idiopathic paraproteinaemia was found in 19% of the cases. A restriction of heterogeneity and an imbalance in the kappa/lambda ratio of the immunoglobulins was seen in a number of other sera. Determinations of immunoglobulin levels in sera of individuals without paraproteinaemia showed an increase in IgA and IgG. The quantitations of the IgG subclasses demonstrated that an increase in the IgG1 and IgG3 subclasses is responsible for the elevated level of the IgG. The variation in the immunoglobulin levels increased significantly with age of IgM and for the three major IgG subclasses. No abnormalities were found in the urine or in the mixed saliva. These results indicate that selective changes in the extent of the antibody-immunoglobulin repertoire characterize the immunoglobulin pattern of ageing man. PMID:1212818

Competitive Inhibitors of the CphA Metallo-β-Lactamase from Aeromonas hydrophila▿

PubMed Central

Horsfall, L. E.; Garau, G.; Liénard, B. M. R.; Dideberg, O.; Schofield, C. J.; Frère, J. M.; Galleni, M.

2007-01-01

Various inhibitors of metallo-β-lactamases have been reported; however, none are effective for all subgroups. Those that have been found to inhibit the enzymes of subclass B2 (catalytically active with one zinc) either contain a thiol (and show less inhibition towards this subgroup than towards the dizinc members of B1 and B3) or are inactivators behaving as substrates for the dizinc family members. The present work reveals that certain pyridine carboxylates are competitive inhibitors of CphA, a subclass B2 enzyme. X-ray crystallographic analyses demonstrate that pyridine-2,4-dicarboxylic acid chelates the zinc ion in a bidentate manner within the active site. Salts of these compounds are already available and undergoing biomedical testing for various nonrelated purposes. Pyridine carboxylates appear to be useful templates for the development of more-complex, selective, nontoxic inhibitors of subclass B2 metallo-β-lactamases. PMID:17307979

A distinctive type of ascending prominence - 'Fountain'

NASA Technical Reports Server (NTRS)

Tandberg-Hanssen, E.; Hansen, R. T.; Riddle, A. C.

1975-01-01

Cinematographic observations of solar prominences made at Mauna Loa, Hawaii, during the past few years suggest that there is a well-defined subclass of ascending prominences characterized by closed-system transference of chromospheric material along an arch or loop (up one leg and down the other). While this occurs, the entire prominence envelope steadily rises upward and expands through the corona. These prominences are denoted as 'fountains'. Several examples are described. Fountains appear to be well contained by coronal magnetic fields. Their total kinetic energy is of the order of 10 to the 30th power erg, but dissipation is typically quite slow (over time periods of 100 min or so), so that the correlative disturbances (radio bursts, coronal transients, chromospheric brightenings) are generally not spectacular or nonexistent.

[Serum immunoglobulin IgG subclass distribution of antibody responses to pertussis toxin and filamentous hemagglutinin of Bordetella pertussis in patients with whooping cough].

PubMed

Rastawicki, Waldemar; Smietańska, Karolina; Rokosz-Chudziak, Natalia; Jagielski, Marek

2013-01-01

The present study was aimed at determining the IgG subclass distribution against pertussis toxin (PT) and filamentous hemagglutinin (FHA) of Bordetella pertussis in patients with whooping cough. The total number of 222 serum samples obtained from patients suspected in clinical investigation for pertussis were tested separately by in-house ELISA for the presence of IgG antibodies to pertussis toxin and filamentous hemagglutinin. The percentage distribution of specific anti-PT and anti-FHA IgG subclass response was calculated only on the basis of group of sera confirmed in the present study as positive for total IgG antibodies (183 sera to PT antigen and 129 to FHA antigen). Paired serum specimens were obtained from 36 patients. Based on the results of determining the level of antibodies in the sera of 40 blood donors, the cut-off limit of serum antibodies for each subclass was set at arithmetic mean plus two standard deviations. Antibodies of IgG1 to pertussis toxin and filamentous hemagglutinin were diagnosed in 151 (82.5%) and 99 (76.7%), IgG2 in 72 (39.0%) and 50 (38.8%), IgG3 in 17 (9.3%) and 43 (33.3%), IgG4 in 55 (30.1%) and 53 (41.1%) serum samples, respectively. There were no significant differences in percentage of sera with IgG1, IgG2 and IgG3 in relation to age of the patients. However, the frequency of occurrence of IgG4 antibodies was highest in the group of the youngest children to the age of 6 years old (61.8% for PT and 68.0% for FHA), and decrease with age, reaching the minimum in the group of patients above 40 years old (13.2% and 4.2% for PT and FHA, respectively). We also found significantly higher frequency of IgG4 to PT and FHA antigens in men than in women. Statistically significant, essential changes in the pattern of IgG subclass during the course of infection were not found. In conclusion, this study showed that all four subclasses of IgG antibodies to pertussis toxin and filamentous hemagglutinin are produced during whooping cough.

Antigen-Specific Antibody Glycosylation Is Regulated via Vaccination.

PubMed

Mahan, Alison E; Jennewein, Madeleine F; Suscovich, Todd; Dionne, Kendall; Tedesco, Jacquelynne; Chung, Amy W; Streeck, Hendrik; Pau, Maria; Schuitemaker, Hanneke; Francis, Don; Fast, Patricia; Laufer, Dagna; Walker, Bruce D; Baden, Lindsey; Barouch, Dan H; Alter, Galit

2016-03-01

Antibody effector functions, such as antibody-dependent cellular cytotoxicity, complement deposition, and antibody-dependent phagocytosis, play a critical role in immunity against multiple pathogens, particularly in the absence of neutralizing activity. Two modifications to the IgG constant domain (Fc domain) regulate antibody functionality: changes in antibody subclass and changes in a single N-linked glycan located in the CH2 domain of the IgG Fc. Together, these modifications provide a specific set of instructions to the innate immune system to direct the elimination of antibody-bound antigens. While it is clear that subclass selection is actively regulated during the course of natural infection, it is unclear whether antibody glycosylation can be tuned, in a signal-specific or pathogen-specific manner. Here, we show that antibody glycosylation is determined in an antigen- and pathogen-specific manner during HIV infection. Moreover, while dramatic differences exist in bulk IgG glycosylation among individuals in distinct geographical locations, immunization is able to overcome these differences and elicit antigen-specific antibodies with similar antibody glycosylation patterns. Additionally, distinct vaccine regimens induced different antigen-specific IgG glycosylation profiles, suggesting that antibody glycosylation is not only programmable but can be manipulated via the delivery of distinct inflammatory signals during B cell priming. These data strongly suggest that the immune system naturally drives antibody glycosylation in an antigen-specific manner and highlights a promising means by which next-generation therapeutics and vaccines can harness the antiviral activity of the innate immune system via directed alterations in antibody glycosylation in vivo.  .

Estimation of divergence times in litostomatean ciliates (Ciliophora: Intramacronucleata), using Bayesian relaxed clock and 18S rRNA gene.

PubMed

Vďačný, Peter

2015-08-01

The class Litostomatea comprises a diverse assemblage of free-living and endosymbiotic ciliates. To understand diversification dynamic of litostomateans, divergence times of their main groups were estimated with the Bayesian molecular dating, a technique allowing relaxation of molecular clock and incorporation of flexible calibration points. The class Litostomatea very likely emerged during the Cryogenian around 680 Mya. The origin of the subclass Rhynchostomatia is dated to about 415 Mya, while that of the subclass Haptoria to about 654 Mya. The order Pleurostomatida, emerging about 556 Mya, was recognized as the oldest group within the subclass Haptoria. The order Spathidiida appeared in the Paleozoic about 442 Mya. The three remaining haptorian orders evolved in the Paleozoic/Mesozoic periods: Didiniida about 419 Mya, Lacrymariida about 269 Mya, and Haptorida about 194 Mya. The subclass Trichostomatia originated from a spathidiid ancestor in the Mesozoic about 260 Mya. A further goal of this study was to investigate the impact of various settings on posterior divergence time estimates. The root placement and tree topology as well as the priors of the rate-drift model, birth-death process and nucleotide substitution rate, had no significant effect on calculation of posterior divergence time estimates. However, removal of calibration points could significantly change time estimates at some nodes. Copyright © 2015 Elsevier GmbH. All rights reserved.

What do anti-Toxoplasma gondii IgA and IgG subclasses in human saliva indicate?

PubMed

Cañedo-Solares, I; Gómez-Chávez, F; Luna-Pastén, H; Ortiz-Alegría, L B; Flores-García, Y; Figueroa-Damián, R; Macedo-Romero, C A; Correa, D

2018-05-01

Diagnostic tests for toxoplasmosis are based on serological techniques due to their high sensitivity. Some IgG subclasses are related to clinical outcome in the congenital form. In this work, we determined the levels of IgG, IgA, IgG1, IgG2, IgG3 and IgG4 anti-Toxoplasma gondii antibodies in paired saliva and serum samples from 91 women by indirect ELISA using a crude extract of the RH strain. The levels of IgA, IgG2, IgG3 and IgG4 antibodies and, to a lesser extent, IgG1 did not correlate between saliva and serum, that is, most cases that were positive for one Ig class in a sample were negative or very low in the other, and vice versa. We also observed that most samples of saliva that were positive for one IgG subclass were also positive for at least 2 of the other 3; this contrasted with findings in serum, wherein each person was positive almost exclusively for one subclass, as demonstrated before by us and other researchers. Although these findings are disappointing for the use in diagnosis, the richer response in saliva might indicate local exposure to T. gondii antigens without systemic infection; thus, saliva might be reflecting a local (protective?) response against this protozoan. © 2018 John Wiley & Sons Ltd.

The isotype repertoire of antibodies against novel UH-RA peptides in rheumatoid arthritis.

PubMed

De Winter, Liesbeth M; Geusens, Piet; Lenaerts, Jan; Vanhoof, Johan; Stinissen, Piet; Somers, Veerle

2016-06-07

Recently, autoantibodies against novel UH-RA peptides (UH-RA.1 and UH-RA.21) were identified as candidate biomarkers for patients with rheumatoid arthritis (RA) who are seronegative for the current diagnostic markers rheumatoid factor and anticitrullinated protein antibodies. Previously, screening for anti-UH-RA autoantibodies was based on measuring the immunoglobulin (Ig) G response. We aimed to investigate whether measurement of other isotypes could improve the performance of diagnostic testing. In addition, assigning the isotype profile might provide valuable information on effector functions of the antibodies. The isotype profile of antibodies against UH-RA.1 and UH-RA.21 was studied. The IgG, IgM, and IgA classes, together with the 4 different IgG subclasses, were determined in 285 patients with RA, 88 rheumatic control subjects, and 90 healthy control subjects. Anti-UH-RA.1 antibodies were primarily of the IgM isotype and twice as prevalent as IgG (IgG3-dominated) and IgA. RA sensitivity when testing for anti-UH-RA.1 IgM was shown to be higher than when testing for the IgG isotype: 18 % versus 9 % sensitivity when RA specificity was set to 90 %. Within antibodies against UH-RA.21, IgG and IgA were more common than IgM. Different anti-UH-RA.21 IgG subclasses were found, with the highest prevalence found for IgG2. Combined testing for IgG and IgA slightly increased RA sensitivity of UH-RA.21-specific antibody testing to 27 % compared with solely testing for IgG (23 %). Notably, a higher number of anti-UH-RA.21 antibody isotypes was related to increased levels of erythrocyte sedimentation rate. Finally, for both antibody responses, the full antibody isotype use was demonstrated in early and seronegative disease. The isotype distribution of anti-UH-RA.1 and anti-UH-RA.21 antibodies was successfully outlined, and, for antibodies against UH-RA.1, we found that isotype-specific testing might have implications for diagnostic testing. The exact mechanisms by which the different antibody isotypes act still have to be unraveled.

Simultaneous profiling of activity patterns in multiple neuronal subclasses.

PubMed

Parrish, R Ryley; Grady, John; Codadu, Neela K; Trevelyan, Andrew J; Racca, Claudia

2018-06-01

Neuronal networks typically comprise heterogeneous populations of neurons. A core objective when seeking to understand such networks, therefore, is to identify what roles these different neuronal classes play. Acquiring single cell electrophysiology data for multiple cell classes can prove to be a large and daunting task. Alternatively, Ca 2+ network imaging provides activity profiles of large numbers of neurons simultaneously, but without distinguishing between cell classes. We therefore developed a strategy for combining cellular electrophysiology, Ca 2+ network imaging, and immunohistochemistry to provide activity profiles for multiple cell classes at once. This involves cross-referencing easily identifiable landmarks between imaging of the live and fixed tissue, and then using custom MATLAB functions to realign the two imaging data sets, to correct for distortions of the tissue introduced by the fixation or immunohistochemical processing. We illustrate the methodology for analyses of activity profiles during epileptiform events recorded in mouse brain slices. We further demonstrate the activity profile of a population of parvalbumin-positive interneurons prior, during, and following a seizure-like event. Current approaches to Ca 2+ network imaging analyses are severely limited in their ability to subclassify neurons, and often rely on transgenic approaches to identify cell classes. In contrast, our methodology is a generic, affordable, and flexible technique to characterize neuronal behaviour with respect to classification based on morphological and neurochemical identity. We present a new approach for analysing Ca 2+ network imaging datasets, and use this to explore the parvalbumin-positive interneuron activity during epileptiform events. Copyright © 2018 Elsevier B.V. All rights reserved.

Sex differences in lipid profiles and treatment utilization among young adults with acute myocardial infarction: Results from the VIRGO study.

PubMed

Lu, Yuan; Zhou, Shengfan; Dreyer, Rachel P; Caulfield, Michael; Spatz, Erica S; Geda, Mary; Lorenze, Nancy P; Herbert, Peter; D'Onofrio, Gail; Jackson, Elizabeth A; Lichtman, Judith H; Bueno, Héctor; Spertus, John A; Krumholz, Harlan M

2017-01-01

Young women with acute myocardial infarction (AMI) have higher mortality risk than similarly aged men. An adverse lipid profile is an important risk factor for cardiovascular outcomes after AMI, but little is known about whether young women with AMI have a higher-risk lipid pattern than men. We characterized sex differences in lipid profiles and treatment utilization among young adults with AMI. A total of 2,219 adults with AMI (1,494 women) aged 18-55 years were enrolled from 103 hospitals in the United States (2008-2012). Serum lipids and lipoprotein subclasses were measured 1 month after discharge. More than 90% of adults were discharged on a statin, but less than half received a high-intensity dose and 12% stopped taking treatments by 1 month. For both men and women, the median of low-density lipoprotein (LDL) cholesterol was reduced to <100 mg/dL 1 month after discharge for AMI, but high-density lipoprotein (HDL) cholesterol remained <40 mg/dL. Multivariate regression analyses showed that young women had favorable lipoprotein profiles compared with men: women had higher HDL cholesterol and HDL large particle, but lower total cholesterol-to-HDL cholesterol ratio and LDL small particle. Young women with AMI had slightly favorable lipid and lipoprotein profiles compared with men, suggesting that difference in lipid and lipoprotein may not be a major contributor to sex differences in outcomes after AMI. In both men and women, statin remained inadequately used, and low HDL cholesterol level was a major lipid abnormality. Copyright © 2016 Elsevier Inc. All rights reserved.

Population density of red langurs in Sabangau tropical peat-swamp forest, Central Kalimantan, Indonesia.

PubMed

Ehlers Smith, David A; Ehlers Smith, Yvette C

2013-08-01

Because of the large-scale destruction of Borneo's rainforests on mineral soils, tropical peat-swamp forests (TPSFs) are increasingly essential for conserving remnant biodiversity, particularly in the lowlands where the majority of habitat conversion has occurred. Consequently, effective strategies for biodiversity conservation are required, which rely on accurate population density and distribution estimates as a baseline. We sought to establish the first population density estimates of the endemic red langur (Presbytis rubicunda) in Sabangau TPSF, the largest remaining contiguous lowland forest-block on Borneo. Using Distance sampling principles, we conducted line transect surveys in two of Sabangau's three principle habitat sub-classes and calculated group density at 2.52 groups km⁻² (95% CI 1.56-4.08) in the mixed-swamp forest sub-class. Based on an average recorded group size of 6.95 individuals, population density was 17.51 ind km⁻², the second highest density recorded in this species. The accessible area of the tall-interior forest, however, was too disturbed to yield density estimates representative of the entire sub-class, and P. rubicunda was absent from the low-pole forest, likely as a result of the low availability of the species' preferred foods. This absence in 30% of Sabangau's total area indicates the importance of in situ population surveys at the habitat-specific level for accurately informing conservation strategies. We highlight the conservation value of TPSFs for P. rubicunda given the high population density and large areas remaining, and recommend 1) quantifying the response of P. rubicunda to the logging and burning of its habitats; 2) surveying degraded TPSFs for viable populations, and 3) effectively delineating TPSF sub-class boundaries from remote imagery to facilitate population estimates across the wider peat landscape, given the stark contrast in densities found across the habitat sub-classes of Sabangau. © 2013 Wiley Periodicals, Inc.

The different effector function capabilities of the seven equine IgG subclasses have implications for vaccine strategies

PubMed Central

Lewis, Melanie J.; Wagner, Bettina; Woof, Jenny M.

2008-01-01

Recombinant versions of the seven equine IgG subclasses were expressed in CHO cells. All assembled into intact immunoglobulins stabilised by disulphide bridges, although, reminiscent of human IgG4, a small proportion of equine IgG4 and IgG7 were held together by non-covalent bonds alone. All seven IgGs were N-glycosylated. In addition IgG3 appeared to be O-glycosylated and could bind the lectin jacalin. Staphylococcal protein A displayed weak binding for the equine IgGs in the order: IgG1 > IgG3 > IgG4 > IgG7 > IgG2 = IgG5 > IgG6. Streptococcal protein G bound strongly to IgG1, IgG4 and IgG7, moderately to IgG3, weakly to IgG2 and IgG6, and not at all to IgG5. Analysis of antibody effector functions revealed that IgG1, IgG3, IgG4, IgG5 and IgG7, but not IgG2 and IgG6, were able to elicit a strong respiratory burst from equine peripheral blood leukocytes, predicting that the former five IgG subclasses are able to interact with Fc receptors on effector cells. IgG1, IgG3, IgG4 and IgG7, but not IgG2, IgG5 and IgG6, were able to bind complement C1q and activate complement via the classical pathway. The differential effector function capabilities of the subclasses suggest that, for maximum efficacy, equine vaccine strategies should seek to elicit antibody responses of the IgG1, IgG3, IgG4, and IgG7 subclasses. PMID:17669496

Validation of the All Patient Refined Diagnosis Related Group (APR-DRG) Risk of Mortality and Severity of Illness Modifiers as a Measure of Perioperative Risk.

PubMed

McCormick, Patrick J; Lin, Hung-Mo; Deiner, Stacie G; Levin, Matthew A

2018-03-22

The All Patient Refined Diagnosis Related Group (APR-DRG) is an inpatient visit classification system that assigns a diagnostic related group, a Risk of Mortality (ROM) subclass and a Severity of Illness (SOI) subclass. While extensively used for cost adjustment, no study has compared the APR-DRG subclass modifiers to the popular Charlson Comorbidity Index as a measure of comorbidity severity in models for perioperative in-hospital mortality. In this study we attempt to validate the use of these subclasses to predict mortality in a cohort of surgical patients. We analyzed all adult (age over 18 years) inpatient non-cardiac surgery at our institution between December 2005 and July 2013. After exclusions, we split the cohort into training and validation sets. We created prediction models of inpatient mortality using the Charlson Comorbidity Index, ROM only, SOI only, and ROM with SOI. Models were compared by receiver-operator characteristic (ROC) curve, area under the ROC curve (AUC), and Brier score. After exclusions, we analyzed 63,681 patient-visits. Overall in-hospital mortality was 1.3%. The median number of ICD-9-CM diagnosis codes was 6 (Q1-Q3 4-10). The median Charlson Comorbidity Index was 0 (Q1-Q3 0-2). When the model was applied to the validation set, the c-statistic for Charlson was 0.865, c-statistic for ROM was 0.975, and for ROM and SOI combined the c-statistic was 0.977. The scaled Brier score for Charlson was 0.044, Brier for ROM only was 0.230, and Brier for ROM and SOI was 0.257. The APR-DRG ROM or SOI subclasses are better predictors than the Charlson Comorbidity Index of in-hospital mortality among surgical patients.

New Perspectives on Acetate and One-Carbon Metabolism in the Methanoarchaea

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ferry, James

Carbonic anhydrases catalyze the reversible hydration of carbon dioxide to bicarbonate. Although widespread in prokaryotes of the domains Bacteria and Archaea, few have been investigated and the physiological functions are largely unknown. Carbonic anhydrases are of biotechnological interest for carbon dioxide capture and sequestration at point sources. Prokaryotes encode three independently evolved classes. The alpha-class is restricted to a few pathogens and the other two are uniformly distributed in phylogenetically and physiologically diverse species. Although wide-spread in prokaryotes, only three gamma-class enzymes have been biochemically characterized and the physiological functions have not been investigated. The gamma-class is prominent in anaerobicmore » acetate-utilizing methane-producing species of the genus Methanosarcina that encode three subclasses. Enzymes from two of the subclasses, Cam and CamH from Methanosarcina thermophila, have been characterized and found to utilize iron in the active site which is the first example of an iron-containing carbonic anhydrase. No representative of the third subclass has been isolated, although this subclass constitutes the great majority of the β-class. This grant application proposed to characterize gamma-class carbonic anhydrases from diverse anaerobic prokaryotes from the domains Bacteria and Archaea to broaden the understanding of this enzyme. In particular, the three subclasses present the genetically tractable acetate-utilizing methanogen Methanosarcina acetivorans will be investigated to extend studies of acetate and one-carbon metabolism in this species. A genetic approach will be taken to ascertain the physiological functions. It is also proposed to delve deeper into the mechanism of Cam from M. thermophila, the archetype of the gamma-class, via a high resolution neutron structure and kinetic analysis of site-specific amino acid replacement variants. In the course of the investigation, goals were added to take advantage of discoveries on enzymes responding to oxidative stress.« less

Effects of sea buckthorn and bilberry on serum metabolites differ according to baseline metabolic profiles in overweight women: a randomized crossover trial.

PubMed

Larmo, Petra S; Kangas, Antti J; Soininen, Pasi; Lehtonen, Henna-Maria; Suomela, Jukka-Pekka; Yang, Baoru; Viikari, Jorma; Ala-Korpela, Mika; Kallio, Heikki P

2013-10-01

Berries are associated with health benefits. Little is known about the effect of baseline metabolome on the overall metabolic responses to berry intake. We studied the effects of berries on serum metabolome. Eighty overweight women completed this randomized crossover study. During the interventions of 30 d, subjects consumed dried sea buckthorn berries (SBs), sea buckthorn oil (SBo), sea buckthorn phenolics ethanol extract mixed with maltodextrin (SBe+MD) (1:1), or frozen bilberries. Metabolic profiles were quantified from serum samples by using (1)H nuclear magnetic resonance spectroscopy. All interventions induced a significant (P < 0.001-0.003) effect on the overall metabolic profiles. The effect was observed both in participants who had a metabolic profile that reflected higher cardiometabolic risk at baseline (group B: P = 0.001-0.008) and in participants who had a lower-risk profile (group A: P < 0.001-0.009). Although most of the changes in individual metabolites were not statistically significant after correction for multiplicity, clear trends were observed. SB-induced effects were mainly on serum triglycerides and very-low-density lipoprotein (VLDL) and its subclasses, which decreased in metabolic group B. SBo induced a decreasing trend in serum total, intermediate-density lipoprotein (IDL), and low-density lipoprotein (LDL) cholesterol and subfractions of IDL and LDL in group B. During the SBe+MD treatment, VLDL fractions and serum triglycerides increased. Bilberries caused beneficial changes in serum lipids and lipoproteins in group B, whereas the opposite was true in group A. Berry intake has overall metabolic effects, which depend on the cardiometabolic risk profile at baseline. This trial was registered at clinicaltrials.gov as NCT01860547.

Effects of sea buckthorn and bilberry on serum metabolites differ according to baseline metabolic profiles in overweight women: a randomized crossover trial1234

PubMed Central

Larmo, Petra S; Kangas, Antti J; Soininen, Pasi; Lehtonen, Henna-Maria; Suomela, Jukka-Pekka; Yang, Baoru; Viikari, Jorma; Ala-Korpela, Mika; Kallio, Heikki P

2013-01-01

Background: Berries are associated with health benefits. Little is known about the effect of baseline metabolome on the overall metabolic responses to berry intake. Objective: We studied the effects of berries on serum metabolome. Design: Eighty overweight women completed this randomized crossover study. During the interventions of 30 d, subjects consumed dried sea buckthorn berries (SBs), sea buckthorn oil (SBo), sea buckthorn phenolics ethanol extract mixed with maltodextrin (SBe+MD) (1:1), or frozen bilberries. Metabolic profiles were quantified from serum samples by using 1H nuclear magnetic resonance spectroscopy. Results: All interventions induced a significant (P < 0.001–0.003) effect on the overall metabolic profiles. The effect was observed both in participants who had a metabolic profile that reflected higher cardiometabolic risk at baseline (group B: P = 0.001–0.008) and in participants who had a lower-risk profile (group A: P < 0.001–0.009). Although most of the changes in individual metabolites were not statistically significant after correction for multiplicity, clear trends were observed. SB-induced effects were mainly on serum triglycerides and very-low-density lipoprotein (VLDL) and its subclasses, which decreased in metabolic group B. SBo induced a decreasing trend in serum total, intermediate-density lipoprotein (IDL), and low-density lipoprotein (LDL) cholesterol and subfractions of IDL and LDL in group B. During the SBe+MD treatment, VLDL fractions and serum triglycerides increased. Bilberries caused beneficial changes in serum lipids and lipoproteins in group B, whereas the opposite was true in group A. Conclusion: Berry intake has overall metabolic effects, which depend on the cardiometabolic risk profile at baseline. This trial was registered at clinicaltrials.gov as NCT01860547. PMID:23945716

[Isolation and characteristics of IgA1 and its use for detecting bacterial IgA1 proteases].

PubMed

Amelina, I P; Zakharova, N A

1984-12-01

Sufficiently purified IgA, subclass I, has been isolated from the defibrinated plasma of a myeloma patient by chromatography on columns packed with DEAE-Sephadex A-50 or Sephadex G-200, and rabbit antiserum to this immunoglobulin has been obtained. These preparations have been used for detecting specific protease in Bordetella pertussis. The tested B. pertussis strains have been shown to induce, as revealed by immunoelectrophoretic methods, the proteolysis of human IgA, subclass I.

Two peculiar subclasses of cool DB stars - The DBA's and the DBZ's

NASA Technical Reports Server (NTRS)

Shipman, Harry L.

1987-01-01

This paper reviews several recent observational investigations which have demonstrated that a significant number of white dwarfs with He-dominated photospheres contain trace hydrogen. In addition, follow-up work on the Case Blue Star survey has uncovered an analog of GD 40 - another DBZ star. Various scenarios for their origin are discussed. The paper concludes with a brief synopsis of a discussion of how many more subclasses of white dwarf stars might exist and what it would take to discover them.

Exploring the Variability of the Fermi LAT Blazar Population

NASA Astrophysics Data System (ADS)

Macomb, Daryl J.; Shrader, C. R.

2014-01-01

The flux variability of the approximately 2000 point sources cataloged by the Fermi Gamma-Ray Space Telescope provide important clues to population characteristics. This is particularly true of the more than 1100 source that are likely AGN. By characterizing the intrinsic flux variability and distinguishing this variability from flaring behavior, we can better address questions of flare amplitudes, durations, recurrence times, and temporal profiles. A better understanding of the responsible physical environments, such as the scale and location of jet structures responsible for the high-energy emission, may emerge from such studies. Assessing these characteristics as a function of blazar sub-class is a further goal in order to address questions about the fundamentals of blazar AGN physics. Here we report on progress made in categorizing blazar flare behavior, and correlate these behaviors with blazar sub-type and other source parameters.

Parkinson’s disease and pesticides: a toxicological perspective

PubMed Central

Hatcher, Jaime M.; Pennell, Kurt D.; Miller, Gary W.

2017-01-01

Environmental factors have been shown to contribute to the incidence of Parkinson’s disease (PD). Pesticides, which represent one of the primary classes of environmental agents associated with PD, share the common feature of being intentionally released into the environment to control or eliminate pests. Pesticides consist of multiple classes and subclasses of insecticides, herbicides, rodenticides, fungicides, fumigants and others and exhibit a vast array of chemically diverse structures. In this review we examine the evidence regarding the ability of each of the major pesticide subclasses to increase the incidence of PD. We propose that, from a toxicological perspective, it would be beneficial to identify specific subclasses, common structural features and the propensity for widespread human exposure when considering the potential role in PD, rather than using the overly broad term of ‘pesticides’ to describe this diverse group of chemicals. Furthermore, these chemicals and their environmentally relevant combinations should be evaluated for their ability to promote or accelerate PD and not merely for being singular causative agents. PMID:18453001

Distribution of IgA subclass response to Coxiella burnetii in patients with acute and chronic Q fever.

PubMed

Camacho, M T; Outschoorn, I; Echevarría, C; Kovácová, E; Yebra, M; Maté, I; Auffray, P; Téllez, A

1998-07-01

The progression of Coxiella burnetii infection to acute or chronic Q fever has been attributed to biological characteristics of the bacterium and to the host immune response. We measured whether serum levels of total and specific subclasses IgA1 and IgA2 could be correlated with the course of disease in acute and chronic Q fever infections, and with the occurrence of endocarditis. In patients with chronic infection, total IgA2 levels were significantly increased. Q-fever-specific IgA1 antibodies were detectable in both acute and chronic infections, but only patients with endocarditis had IgA2 antibodies to C. burnetii phase II antigens. These findings indicate that the measurement of IgA subclasses may be a useful aid in the serological diagnosis of Q fever. Our results reinforce the idea that immunologically mediated host factors are important in the pathogenesis of Q fever and in the disease outcome of this infection. Copyright 1998 Academic Press.

Skin-transmitted pathogens and the heebie jeebies: evidence for a subclass of disgust stimuli that evoke a qualitatively unique emotional response.

PubMed

Blake, Khandis R; Yih, Jennifer; Zhao, Kun; Sung, Billy; Harmon-Jones, Cindy

2017-09-01

Skin-transmitted pathogens have threatened humans since ancient times. We investigated whether skin-transmitted pathogens were a subclass of disgust stimuli that evoked an emotional response that was related to, but distinct from, disgust and fear. We labelled this response "the heebie jeebies". In Study 1, coding of 76 participants' experiences of disgust, fear, and the heebie jeebies showed that the heebie jeebies was elicited by unique stimuli which produced skin-crawling sensations and an urge to protect the skin. In Experiment 2,350 participants' responses to skin-transmitted pathogen, fear-inducing, and disgust-inducing vignettes showed that the vignettes elicited sensations and urges which loaded onto heebie jeebies, fear, and disgust factors, respectively. Experiment 3 largely replicated findings from Experiment 2 using video stimuli (178 participants). Results are consistent with the notion that skin-transmitted pathogens are a subclass of disgust stimuli which motivate behaviours that are functionally consistent with disgust yet qualitatively distinct.

Nonrecurrence and Bell-like inequalities

NASA Astrophysics Data System (ADS)

Danforth, Douglas G.

2017-12-01

The general class, Λ, of Bell hidden variables is composed of two subclasses ΛR and ΛN such that ΛR⋃ΛN = Λ and ΛR∩ ΛN = {}. The class ΛN is very large and contains random variables whose domain is the continuum, the reals. There are an uncountable infinite number of reals. Every instance of a real random variable is unique. The probability of two instances being equal is zero, exactly zero. ΛN induces sample independence. All correlations are context dependent but not in the usual sense. There is no "spooky action at a distance". Random variables, belonging to ΛN, are independent from one experiment to the next. The existence of the class ΛN makes it impossible to derive any of the standard Bell inequalities used to define quantum entanglement.

Strategies for Global Optimization of Temporal Preferences

NASA Technical Reports Server (NTRS)

Morris, Paul; Morris, Robert; Khatib, Lina; Ramakrishnan, Sailesh

2004-01-01

A temporal reasoning problem can often be naturally characterized as a collection of constraints with associated local preferences for times that make up the admissible values for those constraints. Globally preferred solutions to such problems emerge as a result of well-defined operations that compose and order temporal assignments. The overall objective of this work is a characterization of different notions of global preference, and to identify tractable sub-classes of temporal reasoning problems incorporating these notions. This paper extends previous results by refining the class of useful notions of global temporal preference that are associated with problems that admit of tractable solution techniques. This paper also answers the hitherto open question of whether problems that seek solutions that are globally preferred from a Utilitarian criterion for global preference can be found tractably.

Cell-of-Origin DNA Methylation Signatures Are Maintained during Colorectal Carcinogenesis.

PubMed

Bormann, Felix; Rodríguez-Paredes, Manuel; Lasitschka, Felix; Edelmann, Dominic; Musch, Tanja; Benner, Axel; Bergman, Yehudit; Dieter, Sebastian M; Ball, Claudia R; Glimm, Hanno; Linhart, Heinz G; Lyko, Frank

2018-06-12

Colorectal adenomas are precursor lesions of colorectal cancers and represent clonal amplifications of single cells from colonic crypts. DNA methylation patterns specify cell-type identity during cellular differentiation and, therefore, provide opportunities for the molecular analysis of tumors. We have now analyzed DNA methylation patterns in colorectal adenomas and identified three biologically defined subclasses that describe different intestinal crypt differentiation stages. Importantly, colorectal carcinomas could be classified into the same methylation subtypes, reflecting their shared cell types of origin with adenomas. Further data analysis also revealed significantly reduced overall survival for one of the subtypes. Our results provide a concept for understanding the methylation patterns observed in colorectal cancer and provide opportunities for tumor subclassification and patient stratification. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

Microcrustaceans (Branchipoda and Copepoda) of Wetland Impoundments on the Savannah River Site, Aiken, South Carolina

DOE Office of Scientific and Technical Information (OSTI.GOV)

DeBiase, Adrienne E; Taylor, Barbara E

2005-09-21

The United States Department of Energy’s Savannah River Site (SRS) in Aiken, Allendale, and Barnwell Counties, South Carolina, contains an abundance of freshwater wetlands and impoundments. Four large impoundments, as well as several small, abandoned farm and mill ponds, and about 400 Carolina bays and other small, isolated depression wetland ponds are located within the 893 km2 area of the SRS. Crustaceans of the orders Branchiopoda and Copepoda are nearly ubiquitous in these water bodies. Although small in size, these organisms are often very abundant. They consequently play an important trophic role in freshwater food webs supporting fish, larval salamanders,more » larval insects, and numerous other animals, aquatic and terrestrial. This report provides an introduction to the free-living microcrustaceans of lentic water bodies on the SRS and a comprehensive list of species known to occur there. Occurrence patterns are summarized from three extensive survey studies, supplemented with other published and unpublished records. In lieu of a key, we provide a guide to taxonomic resources and notes on undescribed species. Taxa covered include the orders Cladocera, Anostraca, Laevicaudata, and Spinicaudata of the Subclass Branchiopoda and the Superorders Calanoida and Cyclopoida of Subclass Copepoda. Microcrustaceans of the Superorder Harpacticoida of the Subclass Copepoda and Subclass Ostracoda are also often present in lentic water bodies. They are excluded from this report because they have not received much study at the species level on the SRS.« less

Microcrustaceans (Branchiopoda and Copepoda) of Wetland Ponds and Impoundments on the Savannah River Site, Aiken, South Carolina

DOE Office of Scientific and Technical Information (OSTI.GOV)

Adrienne E. DeBiase; Barbara E. Taylor

2005-09-21

The United States Department of Energy's Savannah River Site (SRS) in Aiken, Allendale, and Barnwell Counties, South Carolina, contains an abundance of freshwater wetlands and impoundments. Four large impoundments, as well as several small, abandoned farm and mill ponds, and about 400 Carolina bays and other small, isolated depression wetland ponds are located within the 893 km2 area of the SRS. Crustaceans of the orders Branchiopoda and Copepoda are nearly ubiquitous in these water bodies. Although small in size, these organisms are often very abundant. They consequently play an important trophic role in freshwater food webs supporting fish, larval salamanders,more » larval insects, and numerous other animals, aquatic and terrestrial. This report provides an introduction to the free-living microcrustaceans of lentic water bodies on the SRS and a comprehensive list of species known to occur there. Occurrence patterns are summarized from three extensive survey studies, supplemented with other published and unpublished records. In lieu of a key, we provide a guide to taxonomic resources and notes on undescribed species. Taxa covered include the orders Cladocera, Anostraca, Laevicaudata, and Spinicaudata of the Subclass Branchiopoda and the Superorders Calanoida and Cyclopoida of Subclass Copepoda. Microcrustaceans of the Superorder Harpacticoida of the Subclass Copepoda and Subclass Ostracoda are also often present in lentic water bodies. They are excluded from this report because they have not received much study at the species level on the SRS.« less

Insecticidal properties of a crystal protein gene product isolated from Bacillus thuringiensis subsp. kenyae.

PubMed

Masson, L; Moar, W J; van Frankenhuyzen, K; Bossé, M; Brousseau, R

1992-02-01

A protoxin gene, localized to a high-molecular-weight plasmid from Bacillus thuringiensis subsp. kenyae, was cloned on a 19-kb BamHI DNA fragment into Escherichia coli. Characterization of the gene revealed it to be a member of the CryIE toxin subclass which has been reported to be as toxic as the CryIC subclass to larvae from Spodoptera exigua in assays with crude E. coli extracts. To directly test the purified recombinant gene product, the gene was subcloned as a 4.8-kb fragment into an expression vector resulting in the overexpression of a 134-kDa protein in the form of phase-bright inclusions in E. coli. Treatment of solubilized inclusion bodies with either trypsin or gut juice from the silkworm Bombyx mori resulted in the appearance of a protease-resistant 65-kDa protein. In force-feeding bioassays, the purified activated protein was highly toxic to larvae of B. mori but not to larvae of Choristoneura fumiferana. In diet bioassays with larvae from S. exigua, the purified protoxin was nontoxic. However, prior activation of the protoxin by tryptic digestion resulted in the appearance of some toxic activity. These results demonstrate that this new subclass of protein toxin may not be useful for the control of Spodoptera species as previously reported. Hierarchical clustering of the nine known lepidopteran-specific CryI toxin subclasses through multiple sequence alignment suggests that the toxins fall into four possible subgroups or clusters.

Dietary flavonoid intake and colorectal cancer risk in the European prospective investigation into cancer and nutrition (EPIC) cohort.

PubMed

Zamora-Ros, Raul; Barupal, Dinesh K; Rothwell, Joseph A; Jenab, Mazda; Fedirko, Veronika; Romieu, Isabelle; Aleksandrova, Krasimira; Overvad, Kim; Kyrø, Cecilie; Tjønneland, Anne; Affret, Aurélie; His, Mathilde; Boutron-Ruault, Marie-Christine; Katzke, Verena; Kühn, Tilman; Boeing, Heiner; Trichopoulou, Antonia; Naska, Androniki; Kritikou, Maria; Saieva, Calogero; Agnoli, Claudia; Santucci de Magistris, Maria; Tumino, Rosario; Fasanelli, Francesca; Weiderpass, Elisabete; Skeie, Guri; Merino, Susana; Jakszyn, Paula; Sánchez, Maria-José; Dorronsoro, Miren; Navarro, Carmen; Ardanaz, Eva; Sonestedt, Emily; Ericson, Ulrika; Maria Nilsson, Lena; Bodén, Stina; Bueno-de-Mesquita, H B As; Peeters, Petra H; Perez-Cornago, Aurora; Wareham, Nicholas J; Khaw, Kay-Thee; Freisling, Heinz; Cross, Amanda J; Riboli, Elio; Scalbert, Augustin

2017-04-15

Flavonoids have been shown to inhibit colon cancer cell proliferation in vitro and protect against colorectal carcinogenesis in animal models. However, epidemiological evidence on the potential role of flavonoid intake in colorectal cancer (CRC) development remains sparse and inconsistent. We evaluated the association between dietary intakes of total flavonoids and their subclasses and risk of development of CRC, within the European Prospective Investigation into Cancer and Nutrition (EPIC) study. A cohort of 477,312 adult men and women were recruited in 10 European countries. At baseline, dietary intakes of total flavonoids and individual subclasses were estimated using centre-specific validated dietary questionnaires and composition data from the Phenol-Explorer database. During an average of 11 years of follow-up, 4,517 new cases of primary CRC were identified, of which 2,869 were colon (proximal = 1,298 and distal = 1,266) and 1,648 rectal tumours. No association was found between total flavonoid intake and the risk of overall CRC (HR for comparison of extreme quintiles 1.05, 95% CI 0.93-1.18; p-trend = 0.58) or any CRC subtype. No association was also observed with any intake of individual flavonoid subclasses. Similar results were observed for flavonoid intake expressed as glycosides or aglycone equivalents. Intake of total flavonoids and flavonoid subclasses, as estimated from dietary questionnaires, did not show any association with risk of CRC development. © 2016 UIC.

Embryonic staging and external features of development of the Chimaeroid fish, Callorhinchus milii (Holocephali, Callorhinchidae).

PubMed

Didier, Dominique A; LeClair, Elizabeth E; Vanbuskirk, Dana R

1998-04-01

The development of Callorhinchus milii, a primitive chondrichthyan fish (Subclass Holocephali) is described in detail based on a complete series of embryos from stage 17 to hatching. The external features of these specimens, in comparison with other chondrichthyan embryos, are used to establish the first staging table for any chimaeroid species. Each stage of C. milii is defined by a suite of morphological characters in addition to total length, including the number of somites, extent of external pigmentation, eye size and shape, head flexure, heart morphology, and size and shape of paired and unpaired fins. Particular attention is given to features of the gill arches and associated structures, including external gill filaments and the opercular flap. Embryos of this species also possess a transient rostral bulb, a feature unique to chimaeroids. Embryological development of Callorhinchus milii is similar to that previously described for sharks and batoids (Subclass Elasmobranchii), including the spiny dogfish, Squalus acanthias, the Japanese bullshark, Heterodontus japonicus, the lesser spotted dogfish, Scyliorhinus canicula, the frill shark, Chlamydoselachus anguineus, the guitarfish, Rhinobatus halavi, and the skate, Raja brachyura. Callorhinchus milii is also similar in overall development to another holocephalan, Hydrolagus colliei. A review of previous staging schemes confirms that early morphological development in all three major chondrichthyan lineages (sharks, batoids, and chimaeras) can be correlated using a common set of stages. A uniform staging system is provided that should prove useful in continuing ontogenetic and phylogenetic studies of this entire clade of fishes. J. Morphol. 236:25-47, 1998. © 1998 Wiley-Liss, Inc. Copyright © 1998 Wiley-Liss, Inc.

Demonstration of IgG Subclass (IgG1 and IgG3) in Immuno-Related Hemocytopenia.

PubMed

Shao, Yuanyuan; Qi, Xiao; Fu, Rong; Liu, Hui; Wang, Yihao; Ding, Shaoxue; Wang, Huaquan; Li, Lijuan; Shao, Zonghong

2018-06-01

Immuno-related hemocytopenia (IRH) is defined as idiopathic cytopenia of undetermined significance (ICUS) patients with autoantibodies. In our previous studies, we found that IgG1 levels were increased in IRH patients and might cause the destruction of hematopoietic cells. In this study, we analyzed IgG subclasses in 30 IRH patients (male:female = 13:17, median age 32 years, range 18 - 56), 15 IRH remission patients (IRH-R) (male:female = 6:9, median age 34, range 20 - 52) and 20 normal controls (male:female = 8:12, median age 27, range 24 - 36) by Cytometric Bead Array, Flow Cytometry and Immunohistochemical staining. Levels of IgG1/IgG3 in the bone marrow supernatant of IRH patents, as well as the proportion of CD5+ B lymphocytes and Th2 cells (CD3+CD8-IL-4+) were higher than those of IRH-R patients and normal controls, and IgG1 levels had a positive correlation with the proportion of Th2 cells. In IRH patients, IgG1 and IgG3 were positive on nucleated erythrocytes and granulocytes, which were negative in IRH-R patients and healthy controls and had inverse correlations with hematopoietic function. Using immunohistochemical staining, IgG1 were also detected on bone marrow biopsies of IRH patients. The results indicated that IgG1 and IgG3 autoantibodies in IRH patients might play a key role in the IRH pathogenesis and in the abnormal immune function of IRH patients.

Development, validation and reproducibility of a food frequency questionnaire to measure flavonoid intake in older Australian adults.

PubMed

Kent, Katherine; Charlton, Karen E

2018-02-01

To develop and assess the validity and reproducibility of a food frequency questionnaire (FFQ) to measure total flavonoid intake, and individual flavonoid subclasses, in older adults. Retrospective analysis of flavonoid intake in older adults informed the development of a FFQ to measure flavonoid intake and determine the flavonoid subclasses consumed (anthocyanins, flavan-3-ols, flavones, flavonols and flavanones). Older adults (n = 42, mean age 75.3 ± 8.6 years) attended two interviews 1 month apart where anthropometrics (height and weight), blood pressure (BP), demographic data and a 93-item self-administered FFQ were collected. A 4-day food record (FR) was randomly administered between the two interview dates, and each food item was assigned a flavonoid and flavonoid subclass content using the United States Department of Agriculture flavonoid database. The criterion validity and reproducibility of the FFQ was assessed against a 4-day FR using the Wilcoxon signed-rank sum test, Spearman's correlation coefficient (r), Bland-Altman Plots and Cohen's kappa. Total flavonoid intake was determined (median intake FFQ = 919.3 mg/day, FR = 781.4 mg/day). Tests of validity indicated that the FFQ consistently overestimated total flavonoid intake compared with the 4-day FR. There was a significant difference in estimates between the FFQ and the 4-day FR for total flavonoid intake (Wilcoxon signed-rank sum P < 0.001; Bland-Altman plots indicated large bias and wide limits of agreement), but they were well correlated (Spearman's r 0.93, P < 0.001; Cohen's kappa κ = 0.619, P < 0.001). For individual flavonoid subclasses, the tests of validity indicated greater discrepancy compared with 4-day FR. The FFQ showed high reproducibility for estimating total flavonoid intake (FFQ1vsFFQ2: Wilcoxon signed-rank sum test, P > 0.05; Spearman's r 0.91, P < 0.001; Bland-Altman plots visually showed small, non-significant bias and wide limits of agreement; and Cohen's kappa κ = 0.619, P < 0.001), with a small mean percentage difference (6.7%). For individual flavonoid subclasses, the tests of reproducibility between FFQ1 and FFQ2 showed similarly high reproducibility. The developed FFQ appears suitable for satisfactorily ranking individuals according to total flavonoid intake. The FFQ shows limitations for estimating absolute total flavonoid intake and intake of flavonoid subclasses in comparison to a 4-day FR in terms of overestimating intake. Refinement and further validation of this tool may be required. © 2017 The Authors. Nutrition & Dietetics published by John Wiley & Sons Australia, Ltd on behalf of Dietitians Association of Australia.

Human immunoglobulin allotypes

PubMed Central

Lefranc, Marie-Paule

2009-01-01

More than twenty recombinant monoclonal antibodies are approved as therapeutics. Almost all of these are based on the whole IgG isotype format, but vary in the origin of the variable regions between mouse (chimeric), humanized mouse and fully human sequences; all of those with whole IgG format employ human constant region sequences. Currently, the opposing merits of the four IgG subclasses are considered with respect to the in vivo biological activities considered to be appropriate to the disease indication being treated. Human heavy chain genes also exhibit extensive structural polymorphism(s) and, being closely linked, are inherited as a haplotype. Polymorphisms (allotypes) within the IgG isotype were originally discovered and described using serological reagents derived from humans; demonstrating that allotypic variants can be immunogenic and provoke antibody responses as a result of allo-immunization. The serologically defined allotypes differ widely within and between population groups; therefore, a mAb of a given allotype will, inevitably, be delivered to a cohort of patients homozygous for the alternative allotype. This publication reviews the serologically defined human IgG allotypes and considers the potential for allotype differences to contribute to or potentiate immunogenicity. PMID:20073133

Optimal design of focused experiments and surveys

NASA Astrophysics Data System (ADS)

Curtis, Andrew

1999-10-01

Experiments and surveys are often performed to obtain data that constrain some previously underconstrained model. Often, constraints are most desired in a particular subspace of model space. Experiment design optimization requires that the quality of any particular design can be both quantified and then maximized. This study shows how the quality can be defined such that it depends on the amount of information that is focused in the particular subspace of interest. In addition, algorithms are presented which allow one particular focused quality measure (from the class of focused measures) to be evaluated efficiently. A subclass of focused quality measures is also related to the standard variance and resolution measures from linearized inverse theory. The theory presented here requires that the relationship between model parameters and data can be linearized around a reference model without significant loss of information. Physical and financial constraints define the space of possible experiment designs. Cross-well tomographic examples are presented, plus a strategy for survey design to maximize information about linear combinations of parameters such as bulk modulus, κ =λ+ 2μ/3.

Brain synaptosomes display a diadenosine tetraphosphate (Ap4A)-mediated Ca2+ influx distinct from ATP-mediated influx.

PubMed

Pivorun, E B; Nordone, A

1996-06-01

Studies undertaken to compare the effects of Ap4A and ATP on altering intrasynaptosomal Ca2+ levels from deermouse brain reveal that both ligands induce a rapid influx of extracellular Ca2+. The Ca2+ profile elicited by 167 microM Ap4A is "spike-like" (half-time for decline to baseline, 19.1 +/- 1.2 sec), in contrast to the gradual decline observed with ATP (104.0 +/- 7.4 sec). DIDS (4-4'-diisothiocyano-2,2'-disulfonic acid stilbene) and suramin preincubation alter only the ATP-induced Ca2+ profile. Cross-desensitization studies indicate that prior application of ATP does not significantly affect the Ca2+ influx elicited by Ap4A, and that prior application of Ap4A does not affect the Ca2+ influx elicited by ATP. These results demonstrate that extracellular Ap4A and ATP elicit distinct intrasynaptosomal Ca2+ influx profiles, and suggest that these two nucleotides may be interacting with distinct purinoceptor subclasses or purinoceptor-effector complexes. Subjecting the synaptosomes simultaneously to depolarization and Ap4A, or to depolarization and ATP, induces an additive effect on Ca2+ influx. Preincubation with verapamil negates the effects of depolarization without modifying the ligand-elicited Ca2+ fluxes. These results indicate the presence of Ap4A and ATP ligand-gated channels that may function as modulators of neuronal activity.

Location matters: distinct DNA methylation patterns in GABAergic interneuronal populations from separate microcircuits within the human hippocampus.

PubMed

Ruzicka, W Brad; Subburaju, Sivan; Coyle, Joseph T; Benes, Francine M

2018-01-15

Recent studies describe distinct DNA methylomes among phenotypic subclasses of neurons in the human brain, but variation in DNA methylation between common neuronal phenotypes distinguished by their function within distinct neural circuits remains an unexplored concept. Studies able to resolve epigenetic profiles at the level of microcircuits are needed to illuminate chromatin dynamics in the regulation of specific neuronal populations and circuits mediating normal and abnormal behaviors. The Illumina HumanMethylation450 BeadChip was used to assess genome-wide DNA methylation in stratum oriens GABAergic interneurons sampled by laser-microdissection from two discrete microcircuits along the trisynaptic pathway in postmortem human hippocampus from eight control, eight schizophrenia, and eight bipolar disorder subjects. Data were analysed using the minfi Bioconductor package in R software version 3.3.2. We identified 11 highly significant differentially methylated regions associated with a group of genes with high construct-validity, including multiple zinc finger of the cerebellum gene family members and WNT signaling factors. Genomic locations of differentially methylated regions were highly similar between diagnostic categories, with a greater number of differentially methylated individual cytosine residues between circuit locations in bipolar disorder cases than in schizophrenia or control (42, 7, and 7 differentially methylated positions, respectively). These findings identify distinct DNA methylomes among phenotypically similar populations of GABAergic interneurons functioning within separate hippocampal subfields. These data compliment recent studies describing diverse epigenotypes among separate neuronal subclasses, extending this concept to distinct epigenotypes within similar neuronal phenotypes from separate microcircuits within the human brain. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Lovelock vacua with a recurrent null vector field

NASA Astrophysics Data System (ADS)

Ortaggio, Marcello

2018-02-01

Vacuum solutions of Lovelock gravity in the presence of a recurrent null vector field (a subset of Kundt spacetimes) are studied. We first discuss the general field equations, which constrain both the base space and the profile functions. While choosing a "generic" base space puts stronger constraints on the profile, in special cases there also exist solutions containing arbitrary functions (at least for certain values of the coupling constants). These and other properties (such as the p p - waves subclass and the overlap with VSI, CSI and universal spacetimes) are subsequently analyzed in more detail in lower dimensions n =5 , 6 as well as for particular choices of the base manifold. The obtained solutions describe various classes of nonexpanding gravitational waves propagating, e.g., in Nariai-like backgrounds M2×Σn -2. An Appendix contains some results about general (i.e., not necessarily Kundt) Lovelock vacua of Riemann type III/N and of Weyl and traceless-Ricci type III/N. For example, it is pointed out that for theories admitting a triply degenerate maximally symmetric vacuum, all the (reduced) field equations are satisfied identically, giving rise to large classes of exact solutions.

Management of diffuse low-grade gliomas in adults - use of molecular diagnostics.

PubMed

Buckner, Jan; Giannini, Caterina; Eckel-Passow, Jeanette; Lachance, Daniel; Parney, Ian; Laack, Nadia; Jenkins, Robert

2017-06-01

Diffuse WHO grade II gliomas are histologically and genetically heterogeneous. The 2016 WHO classification redefines grade II gliomas with respect to morphological and molecular tumour alterations: grade II oligodendrogliomas are defined by the presence of whole-arm codeletion in chromosomal arms 1p/19q, whereas isocitrate dehydrogenase (IDH) mutations define subclasses of astrocytoma. Although histological grade remains useful, the prognoses of patients with glioma are more tightly associated with molecular alterations than with grade, and chromosomal and gene array technologies are becoming increasingly beneficial in understanding tumour genetic heterogeneity. The indolent nature of the disease often creates subtle neurological symptoms that can be overlooked or misunderstood, resulting in delayed diagnosis. Seizures often herald the diagnosis, especially in patients who have IDH mutations, which are associated with an increased production of 2-hydroxyglutarate. Treatment paradigms have shifted, owing to new diagnostic criteria and new clinical trial evidence. Patients benefit more from chemoradiation than radiation alone, especially those with tumour IDH1 Arg132His mutations; gross total resection of the tumour, including tumours with IDH mutations, is associated with prolonged survival. Initial observation remains appropriate in patients whose rate of disease growth is not yet completely defined; such patients could include those with completely resected disease and those with 1p/19q codeleted tumours.

Flavonoids, flavonoid subclasses and breast cancer risk: a meta-analysis of epidemiologic studies.

PubMed

Hui, Chang; Qi, Xie; Qianyong, Zhang; Xiaoli, Peng; Jundong, Zhu; Mantian, Mi

2013-01-01

Studies have suggested the chemopreventive effects of flavonoids on carcinogenesis. Yet numbers of epidemiologic studies assessing dietary flavonoids and breast cancer risk have yielded inconsistent results. The association between flavonoids, flavonoid subclasses (flavonols, flavan-3-ols, etc.) and the risk of breast cancer lacks systematic analysis. We aimed to examine the association between flavonoids, each flavonoid subclass (except isoflavones) and the risk of breast cancer by conducting a meta-analysis. We searched for all relevant studies with a prospective cohort or case-control study design published before July 1(st), 2012, using Cochrane library, MEDLINE, EMBASE and PUBMED. Summary relative risks (RR) were calculated using fixed- or random-effects models. All analyses were performed using STATA version 10.0. Twelve studies were included, involving 9 513 cases and 181 906 controls, six of which were prospective cohort studies, and six were case-control studies. We calculated the summary RRs of breast cancer risk for the highest vs lowest categories of each flavonoid subclass respectively. The risk of breast cancer significantly decreased in women with high intake of flavonols (RR=0.88, 95% CI 0.80-0.98) and flavones (RR=0.83, 95% CI: 0.76-0.91) compared with that in those with low intake of flavonols and flavones. However, no significant association of flavan-3-ols (RR=0.93, 95% CI: 0.84-1.02), flavanones (summary RR=0.95, 95% CI: 0.88-1.03), anthocyanins (summary RR=0.97, 95% CI: 0.87-1.08) or total flavonoids (summary RR=0.98, 95% CI: 0.86-1.12) intake with breast cancer risk was observed. Furthermore, summary RRs of 3 case-control studies stratified by menopausal status suggested flavonols, flavones or flavan-3-ols intake is associated with a significant reduced risk of breast cancer in post-menopausal while not in pre-menopausal women. The present study suggests the intake of flavonols and flavones, but not other flavonoid subclasses or total flavonoids, is associated with a decreased risk of breast cancer, especially among post-menopausal women.

Effect of a combination of extract from several plants on cell-mediated and humoral immunity of patients with advanced ovarian cancer.

PubMed

Kormosh, N; Laktionov, K; Antoshechkina, M

2006-05-01

The influence of a plant preparation AdMax (Nulab Inc., Clearwater, FL, USA) on immunity in ovarian cancer patients was studied. The preparation is a combination of dried ethanol/water extracts from roots of Leuzea carthamoides, Rhodiola rosea, Eleutherococcus senticosus and fruits of Schizandra chinensis. Twenty eight patients with stage III-IV epithelial ovarian cancer were treated once with 75 mg/m(2) cisplatin and 600 mg/m(2) cyclophosphamide. Peripheral blood was collected 4 weeks after the chemotherapy. Subclasses of T, B and NK lymphocytes were tested for in the blood samples: CD3, CD4, CD5, CD7, CD8, CD11B, CD16, CD20, CD25, CD38, CD45RA, CD50, CD71 and CD95. Immunoglobulin G, A and M concentrations were also determined. Changes were observed in the following T cell subclasses: CD3, CD4, CD5 and CD8. In patients who took AdMax (270 mg a day) for 4 weeks following the chemotherapy, the mean numbers of the four T cell subclasses were increased in comparison with the mean numbers of the T cell subclasses in patients who did not take AdMax. In patients who took AdMax, the mean amounts of IgG and IgM were also increased. The obtained results suggest that the combination of extracts from adaptogenic plants may boost the suppressed immunity in ovarian cancer patients who are subject to chemotherapy. Copyright 2006 John Wiley & Sons, Ltd.

Nature's starships. I. Observed abundances and relative frequencies of amino acids in meteorites

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cobb, Alyssa K.; Pudritz, Ralph E., E-mail: cobbak@mcmaster.ca, E-mail: pudritz@physics.mcmaster.ca

The class of meteorites called carbonaceous chondrites are examples of material from the solar system which have been relatively unchanged from the time of their initial formation. These meteorites have been classified according to the temperatures and physical conditions of their parent planetesimals. We collate available data on amino acid abundance in these meteorites and plot the concentrations of different amino acids for each meteorite within various meteorite subclasses. We plot average concentrations for various amino acids across meteorites separated by subclass and petrologic type. We see a predominance in the abundance and variety of amino acids in CM2 andmore » CR2 meteorites. The range in temperature corresponding to these subclasses indicates high degrees of aqueous alteration, suggesting aqueous synthesis of amino acids. Within the CM2 and CR2 subclasses, we identify trends in relative frequencies of amino acids to investigate how common amino acids are as a function of their chemical complexity. These two trends (total abundance and relative frequencies) can be used to constrain formation parameters of amino acids within planetesimals. Our organization of the data supports an onion shell model for the temperature structure of planetesimals. The least altered meteorites (type 3) and their amino acids originated near cooler surface regions. The most active amino acid synthesis likely took place at intermediate depths (type 2). The most altered materials (type 1) originated furthest toward parent body cores. This region is likely too hot to either favor amino acid synthesis or for amino acids to be retained after synthesis.« less

Nuclear Function of Subclass I Actin-Depolymerizing Factor Contributes to Susceptibility in Arabidopsis to an Adapted Powdery Mildew Fungus1[OPEN

PubMed Central

Inada, Noriko; Higaki, Takumi; Hasezawa, Seiichiro

2016-01-01

Actin-depolymerizing factors (ADFs) are conserved proteins that function in regulating the structure and dynamics of actin microfilaments in eukaryotes. In this study, we present evidence that Arabidopsis (Arabidopsis thaliana) subclass I ADFs, particularly ADF4, functions as a susceptibility factor for an adapted powdery mildew fungus. The null mutant of ADF4 significantly increased resistance against the adapted powdery mildew fungus Golovinomyces orontii. The degree of resistance was further enhanced in transgenic plants in which the expression of all subclass I ADFs (i.e. ADF1–ADF4) was suppressed. Microscopic observations revealed that the enhanced resistance of adf4 and ADF1-4 knockdown plants (ADF1-4Ri) was associated with the accumulation of hydrogen peroxide and cell death specific to G. orontii-infected cells. The increased resistance and accumulation of hydrogen peroxide in ADF1-4Ri were suppressed by the introduction of mutations in the salicylic acid- and jasmonic acid-signaling pathways but not by a mutation in the ethylene-signaling pathway. Quantification by microscopic images detected an increase in the level of actin microfilament bundling in ADF1-4Ri but not in adf4 at early G. orontii infection time points. Interestingly, complementation analysis revealed that nuclear localization of ADF4 was crucial for susceptibility to G. orontii. Based on its G. orontii-infected-cell-specific phenotype, we suggest that subclass I ADFs are susceptibility factors that function in a direct interaction between the host plant and the powdery mildew fungus. PMID:26747284

Angular Distribution of Gamma-Ray Bursts: An Observational Probe of Cosmological Principle

NASA Astrophysics Data System (ADS)

Mészáros, A.; Balázs, L. G.; Vavrek, R.; Horváth, I.; Bagoly, Z.

The test of the isotropy in the angular distribution of the gamma-ray bursts collected in BATSE Catalog (Meegan C. A. et al., http://www.batse.msfc.nasa.gov/data, 2000) is a test of cosmological principle itself, because the gamma-ray bursts are at cosmological distances. Several articles of the authors study this question (Balázs L. G., Mészáros A., & Horváth I., Astron. Astrophys., 339, 1, 1998; Balázs L. G., Mészáros A., Horváth I., & Vavrek R., Astron. Astrophys. Suppl., 138, 417, 1999; Mészáros A., Bagoly Z., & Vavrek R. Astron. Astrophys., in press, 2000). The final conclusion concerning the validity of isotropy is complicated both by instrumental effects and by the fact that there are three subgroups of gamma-ray bursts ("short", "intermediate", "long"; separation is done with respect to the duration of bursts). The long bursts are surely up to z ≃ 4 (z is the redshift); for the remaining two subclasses the redshifts are unknown. The done tests of isotropy suggest (after the elimination of instrumental effects) the existence of anisotropy for the intermediate subclass on the confidence level > 95%. On the other hand, for the remaining two subclasses the situation is unclear; there is no unambiguous rejection of isotropy for them yet on the higher than 95% confidence level. If the bursts of intermediate subclass are at high z-s (say, at, z > 0.1), then the validity of cosmological principle would be at a serious doubt.

OBSERVATIONS OF ROTATING RADIO TRANSIENTS WITH THE FIRST STATION OF THE LONG WAVELENGTH ARRAY

DOE Office of Scientific and Technical Information (OSTI.GOV)

Taylor, G. B.; Stovall, K.; McCrackan, M.

2016-11-10

Rotating radio transients (RRATs) are a subclass of pulsars first identified in 2006 that are detected only in searches for single pulses and not through their time averaged emission. Here, we present the results of observations of 19 RRATs using the first station of the Long Wavelength Array (LWA1) at frequencies between 30 and 88 MHz. The RRATs observed here were first detected in higher frequency pulsar surveys. Of the 19 RRATs observed, two sources were detected and their dispersion measures, periods, pulse profiles, and flux densities are reported and compared to previous higher frequency measurements. We find a lowmore » detection rate (11%), which could be a combination of the lower sensitivity of LWA1 compared to higher frequency telescopes, and the result of scattering by the interstellar medium or a spectral turnover.« less

Stacking Searches for Greater Than 100 MeV Gamma Ray Emission from Radio Galaxies and Seyfert Galaxies

NASA Technical Reports Server (NTRS)

Cillis, A. N.; Hartman, R. C.; Bertsch, D. L.

2003-01-01

The EGRET telescope on CGRO detected more than sixty sources of high-energy gamma radiation associated with active galactic nuclei (AGN). All but one of those belong to the blazar subclass; the only exception is the nearby radio galaxy Centaurus A. Since there is no obvious reason other than proximity to expect Cen A to be the only non-blazar AGN emitting in high-energy gamma rays, we have utilized the "stacking" technique to search for $>100$-MeV emission from two non-blazar AGN subclasses, radio galaxies and Seyfert galaxies. Maps of gamma-ray counts, exposure, and diffuse background have been created, then co-added in varying numbers based on sorts by redshift, 5-GHZ flux density, and optical brightness, and finally tested for gamma-ray emission. No detection significance greater than $2\\sigma$ has been found for any subclass, sorting parameter, or number of objects co-added. Monte Carlo simulations have also been performed, to validate the technique and estimate the significance of the results.

Di-codon Usage for Gene Classification

NASA Astrophysics Data System (ADS)

Nguyen, Minh N.; Ma, Jianmin; Fogel, Gary B.; Rajapakse, Jagath C.

Classification of genes into biologically related groups facilitates inference of their functions. Codon usage bias has been described previously as a potential feature for gene classification. In this paper, we demonstrate that di-codon usage can further improve classification of genes. By using both codon and di-codon features, we achieve near perfect accuracies for the classification of HLA molecules into major classes and sub-classes. The method is illustrated on 1,841 HLA sequences which are classified into two major classes, HLA-I and HLA-II. Major classes are further classified into sub-groups. A binary SVM using di-codon usage patterns achieved 99.95% accuracy in the classification of HLA genes into major HLA classes; and multi-class SVM achieved accuracy rates of 99.82% and 99.03% for sub-class classification of HLA-I and HLA-II genes, respectively. Furthermore, by combining codon and di-codon usages, the prediction accuracies reached 100%, 99.82%, and 99.84% for HLA major class classification, and for sub-class classification of HLA-I and HLA-II genes, respectively.

Genome-wide identification and expression analysis of the ClTCP transcription factors in Citrullus lanatus.

PubMed

Shi, Pibiao; Guy, Kateta Malangisha; Wu, Weifang; Fang, Bingsheng; Yang, Jinghua; Zhang, Mingfang; Hu, Zhongyuan

2016-04-12

The plant-specific TCP transcription factor family, which is involved in the regulation of cell growth and proliferation, performs diverse functions in multiple aspects of plant growth and development. However, no comprehensive analysis of the TCP family in watermelon (Citrullus lanatus) has been undertaken previously. A total of 27 watermelon TCP encoding genes distributed on nine chromosomes were identified. Phylogenetic analysis clustered the genes into 11 distinct subgroups. Furthermore, phylogenetic and structural analyses distinguished two homology classes within the ClTCP family, designated Class I and Class II. The Class II genes were differentiated into two subclasses, the CIN subclass and the CYC/TB1 subclass. The expression patterns of all members were determined by semi-quantitative PCR. The functions of two ClTCP genes, ClTCP14a and ClTCP15, in regulating plant height were confirmed by ectopic expression in Arabidopsis wild-type and ortholog mutants. This study represents the first genome-wide analysis of the watermelon TCP gene family, which provides valuable information for understanding the classification and functions of the TCP genes in watermelon.

Phylogenetic relationships of the Fox (Forkhead) gene family in the Bilateria

NASA Technical Reports Server (NTRS)

Mazet, Francoise; Yu, Jr Kai; Liberles, David A.; Holland, Linda Z.; Shimeld, Sebastian M.

2003-01-01

The Forkhead or Fox gene family encodes putative transcription factors. There are at least four Fox genes in yeast, 16 in Drosophila melanogaster (Dm) and 42 in humans. Recently, vertebrate Fox genes have been classified into 17 groups named FoxA to FoxQ. Here, we extend this analysis to invertebrates, using available sequences from D. melanogaster, Anopheles gambiae (Ag), Caenorhabditis elegans (Ce), the sea squirt Ciona intestinalis (Ci) and amphioxus Branchiostoma floridae (Bf), from which we also cloned several Fox genes. Phylogenetic analyses lend support to the previous overall subclassification of vertebrate genes, but suggest that four subclasses (FoxJ, L, N and Q) could be further subdivided to reflect their relationships to invertebrate genes. We were unable to identify orthologs of Fox subclasses E, H, I, J, M and Q1 in D. melanogaster, A. gambiae or C. elegans, suggesting either considerable loss in ecdysozoans or the evolution of these subclasses in the deuterostome lineage. Our analyses suggest that the common ancestor of protostomes and deuterostomes had a minimum complement of 14 Fox genes.

A subclass of plant heat shock cognate 70 chaperones carries a motif that facilitates trafficking through plasmodesmata

PubMed Central

Aoki, Koh; Kragler, Friedrich; Xoconostle-Cázares, Beatriz; Lucas, William J.

2002-01-01

Plasmodesmata establish a pathway for the trafficking of non-cell-autonomously acting proteins and ribonucleoprotein complexes. Plasmodesmal enriched cell fractions and the contents of enucleate sieve elements, in the form of phloem sap, were used to isolate and characterize heat shock cognate 70 (Hsc70) chaperones associated with this cell-to-cell transport pathway. Three Cucurbita maxima Hsc70 chaperones were cloned and functional and sequence analysis led to the identification of a previously uncharacterized subclass of non-cell-autonomous chaperones. The highly conserved nature of the heat shock protein 70 (Hsp70) family, in conjunction with mutant analysis, permitted the characterization of a motif that allows these Hsc70 chaperones to engage the plasmodesmal non-cell-autonomous translocation machinery. Proof of concept that this motif is necessary for Hsp70 gain-of-movement function was obtained through the engineering of a human Hsp70 that acquired the capacity to traffic through plasmodesmata. These results are discussed in terms of the roles likely played by this subclass of Hsc70 chaperones in the trafficking of non-cell-autonomous proteins. PMID:12456884

Intervention Trials with the Mediterranean Diet in Cardiovascular Prevention: Understanding Potential Mechanisms through Metabolomic Profiling.

PubMed

Martínez-González, Miguel Á; Ruiz-Canela, Miguel; Hruby, Adela; Liang, Liming; Trichopoulou, Antonia; Hu, Frank B

2016-03-09

Large observational epidemiologic studies and randomized trials support the benefits of a Mediterranean dietary pattern on cardiovascular disease (CVD). Mechanisms postulated to mediate these benefits include the reduction of low-grade inflammation, increased adiponectin concentrations, decreased blood coagulation, enhanced endothelial function, lower oxidative stress, lower concentrations of oxidized LDL, and improved apolipoprotein profiles. However, the metabolic pathways through which the Mediterranean diet influences CVD risk remain largely unknown. Investigating specific mechanisms in the context of a large intervention trial with the use of high-throughput metabolomic profiling will provide more solid public health messages and may help to identify key molecular targets for more effective prevention and management of CVD. Although metabolomics is not without its limitations, the techniques allow for an assessment of thousands of metabolites, providing wide-ranging profiling of small molecules related to biological status. Specific candidate plasma metabolites that may be associated with CVD include branched-chain and aromatic amino acids; the glutamine-to-glutamate ratio; some short- to medium-chain acylcarnitines; gut flora metabolites (choline, betaine, and trimethylamine N-oxide); urea cycle metabolites (citrulline and ornithine); and specific lipid subclasses. In addition to targeted metabolites, the role of a large number of untargeted metabolites should also be assessed. Large intervention trials with the use of food patterns for the prevention of CVD provide an unparalleled opportunity to examine the effects of these interventions on plasma concentrations of specific metabolites and determine whether such changes mediate the benefits of the dietary interventions on CVD risk. © 2016 American Society for Nutrition.

A review on interleukins: The key manipulators in rheumatoid arthritis.

PubMed

Sharma, Jatin; Bhar, Sutonuka; Devi, C Subathra

2017-09-01

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease associated with weakening of bones and joint pain. It primarily involves autoimmunity, matrix destruction, osteoclastogenesis, inflammation, and angiogenesis. Numerous cellular and humoral components of the immune system are involved in the etiology of diseases; however, the cardinal part is played by the inter-cellular signaling messengers called cytokines. Interleukins is a vaguely defined sub-class of cytokines that are abundantly found in the RA patients. The multifariousness and diversity in the function of the interleukins make them very likely to be associated with the pathogenesis in multiple ways. Nonetheless, the variety in opinions of researchers globally has led to contentious inferences. Ergo, in this review we have amalgamated the views of researchers from the past two decades till date to provide a comprehensive report about the role of interleukins in rheumatoid arthritis.

Study for standardization of the lighting system in fruit sorting

NASA Astrophysics Data System (ADS)

Gomes, J. F. S.; Baldner, F. O.; Costa, P. B.; Guedes, M. B.; Oliveira, I. A. A.; Leta, F. R.

2016-07-01

Sorting is a very important step in the fruit processing. The attributes definition and characterization are important for both marketing and end user, making it necessary to establish regulations for classification and standardization in order to unify the language of the market and enabling a more efficient market and also increase consumer awareness. For this end, it is necessary to standardize the technical criteria that can change the perception of the product. Studies have been developed in order to standardize a methodology to determine the subclass of fruit ripening, evaluating the influence of different light sources in the subclass evaluation.

Marginal and joint distributions of S100, HMB-45, and Melan-A across a large series of cutaneous melanomas.

PubMed

Viray, Hollis; Bradley, William R; Schalper, Kurt A; Rimm, David L; Gould Rothberg, Bonnie E

2013-08-01

The distribution of the standard melanoma antibodies S100, HMB-45, and Melan-A has been extensively studied. Yet, the overlap in their expression is less well characterized. To determine the joint distributions of the classic melanoma markers and to determine if classification according to joint antigen expression has prognostic relevance. S100, HMB-45, and Melan-A were assayed by immunofluorescence-based immunohistochemistry on a large tissue microarray of 212 cutaneous melanoma primary tumors and 341 metastases. Positive expression for each antigen required display of immunoreactivity for at least 25% of melanoma cells. Marginal and joint distributions were determined across all markers. Bivariate associations with established clinicopathologic covariates and melanoma-specific survival analyses were conducted. Of 322 assayable melanomas, 295 (91.6%), 203 (63.0%), and 236 (73.3%) stained with S100, HMB-45, and Melan-A, respectively. Twenty-seven melanomas, representing a diverse set of histopathologic profiles, were S100 negative. Coexpression of all 3 antibodies was observed in 160 melanomas (49.7%). Intensity of endogenous melanin pigment did not confound immunolabeling. Among primary tumors, associations with clinicopathologic parameters revealed a significant relationship only between HMB-45 and microsatellitosis (P = .02). No significant differences among clinicopathologic criteria were observed across the HMB-45/Melan-A joint distribution categories. Neither marginal HMB-45 (P = .56) nor Melan-A (P = .81), or their joint distributions (P = .88), was associated with melanoma-specific survival. Comprehensive characterization of the marginal and joint distributions for S100, HMB-45, and Melan-A across a large series of cutaneous melanomas revealed diversity of expression across this group of antigens. However, these immunohistochemically defined subclasses of melanomas do not significantly differ according to clinicopathologic correlates or outcome.

Perfluoroalkyl sulfonic and carboxylic acids: a critical review of physicochemical properties, levels and patterns in waters and wastewaters, and treatment methods.

PubMed

Rayne, Sierra; Forest, Kaya

2009-10-01

Perfluorinated acids (PFAs) are an emerging class of environmental contaminants present in various environmental and biological matrices. Two major PFA subclasses are the perfluorinated sulfonic acids (PFSAs) and carboxylic acids (PFCAs). The physicochemical properties and partitioning behavior for the linear PFA members are poorly understood and widely debated. Even less is known about the numerous branched congeners with varying perfluoroalkyl chain lengths, leading to confounding issues around attempts to constrain the properties of PFAs. Current computational methods are not adequate for reliable multimedia modeling efforts and risk assessments. These compounds are widely present in surface, ground, marine, and drinking waters at concentrations that vary from pg L(-1) to microg L(-1). Concentration gradients of up to several orders of magnitude are observed in all types of aquatic systems and reflect proximity to known industrial sources concentrated near populated regions. Some wastewaters contain PFAs at mg L(-1) to low g L(-1) levels, or up to 10 orders of magnitude higher than present in more pristine receiving waters. With the exception of trifluoroacetic acid, which is thought to have both significant natural and anthropogenic sources, all PFSAs and PFCAs are believed to arise from human activities. Filtration and sorption technologies offer the most promising existing removal methods for PFAs in aqueous waste streams, although sonochemical approaches hold promise. Additional studies need to be conducted to better define opportunities from evaporative, extractive, thermal, advanced oxidative, direct and catalyzed photochemical, reductive, and biodegradation methods. Most PFA treatment methods exhibit slow kinetic profiles, hindering their direct application in conventional low hydraulic residence time systems.

Distinct subclassification of DRG neurons innervating the distal colon and glans penis/distal urethra based on the electrophysiological current signature

PubMed Central

Petruska, Jeffrey C.; Cooper, Brian Y.; Johnson, Richard D.

2014-01-01

Spinal sensory neurons innervating visceral and mucocutaneous tissues have unique microanatomic distribution, peripheral modality, and physiological, pharmacological, and biophysical characteristics compared with those neurons that innervate muscle and cutaneous tissues. In previous patch-clamp electrophysiological studies, we have demonstrated that small- and medium-diameter dorsal root ganglion (DRG) neurons can be subclassified on the basis of their patterns of voltage-activated currents (VAC). These VAC-based subclasses were highly consistent in their action potential characteristics, responses to algesic compounds, immunocytochemical expression patterns, and responses to thermal stimuli. For this study, we examined the VAC of neurons retrogradely traced from the distal colon and the glans penis/distal urethra in the adult male rat. The afferent population from the distal colon contained at least two previously characterized cell types observed in somatic tissues (types 5 and 8), as well as four novel cell types (types 15, 16, 17, and 18). In the glans penis/distal urethra, two previously described cell types (types 6 and 8) and three novel cell types (types 7, 14, and 15) were identified. Other characteristics, including action potential profiles, responses to algesic compounds (acetylcholine, capsaicin, ATP, and pH 5.0 solution), and neurochemistry (expression of substance P, CGRP, neurofilament, TRPV1, TRPV2, and isolectin B4 binding) were consistent for each VAC-defined subgroup. With identification of distinct DRG cell types that innervate the distal colon and glans penis/distal urethra, future in vitro studies related to the gastrointestinal and urogenital sensory function in normal as well as abnormal/pathological conditions may be benefitted. PMID:24872531

Distinct subclassification of DRG neurons innervating the distal colon and glans penis/distal urethra based on the electrophysiological current signature.

PubMed

Rau, Kristofer K; Petruska, Jeffrey C; Cooper, Brian Y; Johnson, Richard D

2014-09-15

Spinal sensory neurons innervating visceral and mucocutaneous tissues have unique microanatomic distribution, peripheral modality, and physiological, pharmacological, and biophysical characteristics compared with those neurons that innervate muscle and cutaneous tissues. In previous patch-clamp electrophysiological studies, we have demonstrated that small- and medium-diameter dorsal root ganglion (DRG) neurons can be subclassified on the basis of their patterns of voltage-activated currents (VAC). These VAC-based subclasses were highly consistent in their action potential characteristics, responses to algesic compounds, immunocytochemical expression patterns, and responses to thermal stimuli. For this study, we examined the VAC of neurons retrogradely traced from the distal colon and the glans penis/distal urethra in the adult male rat. The afferent population from the distal colon contained at least two previously characterized cell types observed in somatic tissues (types 5 and 8), as well as four novel cell types (types 15, 16, 17, and 18). In the glans penis/distal urethra, two previously described cell types (types 6 and 8) and three novel cell types (types 7, 14, and 15) were identified. Other characteristics, including action potential profiles, responses to algesic compounds (acetylcholine, capsaicin, ATP, and pH 5.0 solution), and neurochemistry (expression of substance P, CGRP, neurofilament, TRPV1, TRPV2, and isolectin B4 binding) were consistent for each VAC-defined subgroup. With identification of distinct DRG cell types that innervate the distal colon and glans penis/distal urethra, future in vitro studies related to the gastrointestinal and urogenital sensory function in normal as well as abnormal/pathological conditions may be benefitted. Copyright © 2014 the American Physiological Society.

National Soil Information System in Turkey

NASA Astrophysics Data System (ADS)

Emrah Erdogan, Hakki; Sahin, Mehmet; Sahin, Yuksel

2013-04-01

Land consolidation (LC) represents complexity if management, legal, economic and technical procedures realized in order to adjust the land structure according to actual human preferences and needs. It includes changes in ownership rights to land and other real estate property, exchange of parcels among owners, changes in parcel borders, parcel size and shape, joining and dividing of parcels, changes in land use, construction works as roads, bridges, water changes etc.. Since the subject of LC is agricultural lands, the quality of consolidation depends on the quality of soil data. General Directorate of Agrarian Reform (GDAR) is the responsible institution on land consolidation whole of Turkey. Under GDAR, National Soil Information System (NSIS) has been build up with base soil data in relevant scale (1:5000). NSIS contain detailed information on soil chemical and physical properties, current land use, parent material, land capability class, Storie Index Values. SI were used on land consolidation, land use planning and farm development services. LCC was used for land distribution, rental land; define of village settlement, consolidation, expropriation, reconstruction, reclamation, non-agricultural usage. LCC were also specified to subclasses in four different limited factors as i) flow and erosion risk ii) requirement of drainage and soil moisture iii) Limits of soil tillage and root (shallow soils, low water retention capacity, stony, salty .etc) iv) climatic limits. In this study, digital soil survey and mapping project located in Yumurtalik, Adana is presented as an example of NSIS data structure. The project cover an area of 45709 ha that include crop lands as an area of 28528 ha and other land use (urban, roads..etc) as an area of 17181 ha. Soil profiles were described in 45 different points and totally 1279 soil samples were collected in field study and the check bore hole were made in 3170 points.

Optimization of incubation conditions of Plasmodium falciparum antibody multiplex assays to measure IgG, IgG1-4, IgM and IgE using standard and customized reference pools for sero-epidemiological and vaccine studies.

PubMed

Ubillos, Itziar; Jiménez, Alfons; Vidal, Marta; Bowyer, Paul W; Gaur, Deepak; Dutta, Sheetij; Gamain, Benoit; Coppel, Ross; Chauhan, Virander; Lanar, David; Chitnis, Chetan; Angov, Evelina; Beeson, James; Cavanagh, David; Campo, Joseph J; Aguilar, Ruth; Dobaño, Carlota

2018-06-01

The quantitative suspension array technology (qSAT) is a useful platform for malaria immune marker discovery. However, a major challenge for large sero-epidemiological and malaria vaccine studies is the comparability across laboratories, which requires the access to standardized control reagents for assay optimization, to monitor performance and improve reproducibility. Here, the Plasmodium falciparum antibody reactivities of the newly available WHO reference reagent for anti-malaria human plasma (10/198) and of additional customized positive controls were examined with seven in-house qSAT multiplex assays measuring IgG, IgG 1-4 subclasses, IgM and IgE against a panel of 40 antigens. The different positive controls were tested at different incubation times and temperatures (4 °C overnight, 37 °C 2 h, room temperature 1 h) to select the optimal conditions. Overall, the WHO reference reagent had low IgG2, IgG4, IgM and IgE, and also low anti-CSP antibody levels, thus this reagent was enriched with plasmas from RTS,S-vaccinated volunteers to be used as standard for CSP-based vaccine studies. For the IgM assay, another customized plasma pool prepared with samples from malaria primo-infected adults with adequate IgM levels proved to be more adequate as a positive control. The range and magnitude of IgG and IgG 1-4 responses were highest when the WHO reference reagent was incubated with antigen-coupled beads at 4 °C overnight. IgG levels measured in the negative control did not vary between incubations at 37 °C 2 h and 4 °C overnight, indicating no difference in unspecific binding. With this study, the immunogenicity profile of the WHO reference reagent, including seven immunoglobulin isotypes and subclasses, and more P. falciparum antigens, also those included in the leading RTS,S malaria vaccine, was better characterized. Overall, incubation of samples at 4 °C overnight rendered the best performance for antibody measurements against the antigens tested. Although the WHO reference reagent performed well to measure IgG to the majority of the common P. falciparum blood stage antigens tested, customized pools may need to be used as positive controls depending on the antigens (e.g. pre-erythrocytic proteins of low natural immunogenicity) and isotypes/subclasses (e.g. IgM) under study.

Short-term isocaloric fructose restriction lowers apoC-III levels and yields less atherogenic lipoprotein profiles in children with obesity and metabolic syndrome.

PubMed

Gugliucci, Alejandro; Lustig, Robert H; Caccavello, Russell; Erkin-Cakmak, Ayca; Noworolski, Susan M; Tai, Viva W; Wen, Michael J; Mulligan, Kathleen; Schwarz, Jean-Marc

2016-10-01

Dietary fructose may play a role in the pathogenesis of metabolic syndrome (MetS). In a recently published study of obese children with MetS, we showed that isocaloric fructose restriction reduced fasting triglyceride (TG) and LDL-cholesterol (LDL-C). In these ancillary analyses, we tested the hypothesis that these effects were also accompanied by improved quantitative and qualitative changes in LDL and HDL subclasses and their apolipoproteins; as well as change in VLDL, particularly apoC-III. Obese children with MetS (n = 37) consumed a diet that matched self-reported macronutrient composition for nine days, with the exception that dietary fructose was reduced from 11.7 ± 4.0% to 3.8 ± 0.5% of daily calories and substituted with glucose (in starch). Participants underwent fasting biochemical analyses on Days 0 and 10. HDL and LDL subclasses were analyzed using the Lipoprint HDL and LDL subfraction analysis systems from Quantimetrix. Significant reductions in apoB (78 ± 24 vs. 66 ± 24 mg/dl) apoC-III (8.7 ± 3.5 vs. 6.5 ± 2.6 mg/dl) and apoE (4.6 ± 2.3 vs. 3.6 ± 1.1 mg/dl), all p < 0.001) were observed. LDL size increased by 0.87 Å (p = 0.008). Small dense LDL was present in 25% of our cohort and decreased by 68% (p = 0.04). Small HDL decreased by 2.7% (p < 0.001) and large HDL increased by 2.4% (p = 0.04). The TG/HDL-C ratio decreased from 3.1 ± 2.5 to 2.4 ± 1.4 (p = 0.02). These changes in fasting lipid profiles correlated with changes in insulin sensitivity. Isocaloric fructose restriction for 9 days improved lipoprotein markers of CVD risk in children with obesity and MetS. The most dramatic reduction was seen for apoC-III, which has been associated with atherogenic hypertriglyceridemia. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Recognition of handwritten similar Chinese characters by self-growing probabilistic decision-based neural network.

PubMed

Fu, H C; Xu, Y Y; Chang, H Y

1999-12-01

Recognition of similar (confusion) characters is a difficult problem in optical character recognition (OCR). In this paper, we introduce a neural network solution that is capable of modeling minor differences among similar characters, and is robust to various personal handwriting styles. The Self-growing Probabilistic Decision-based Neural Network (SPDNN) is a probabilistic type neural network, which adopts a hierarchical network structure with nonlinear basis functions and a competitive credit-assignment scheme. Based on the SPDNN model, we have constructed a three-stage recognition system. First, a coarse classifier determines a character to be input to one of the pre-defined subclasses partitioned from a large character set, such as Chinese mixed with alphanumerics. Then a character recognizer determines the input image which best matches the reference character in the subclass. Lastly, the third module is a similar character recognizer, which can further enhance the recognition accuracy among similar or confusing characters. The prototype system has demonstrated a successful application of SPDNN to similar handwritten Chinese recognition for the public database CCL/HCCR1 (5401 characters x200 samples). Regarding performance, experiments on the CCL/HCCR1 database produced 90.12% recognition accuracy with no rejection, and 94.11% accuracy with 6.7% rejection, respectively. This recognition accuracy represents about 4% improvement on the previously announced performance. As to processing speed, processing before recognition (including image preprocessing, segmentation, and feature extraction) requires about one second for an A4 size character image, and recognition consumes approximately 0.27 second per character on a Pentium-100 based personal computer, without use of any hardware accelerator or co-processor.

Pan-cancer stratification of solid human epithelial tumors and cancer cell lines reveals commonalities and tissue-specific features of the CpG island methylator phenotype.

PubMed

Sánchez-Vega, Francisco; Gotea, Valer; Margolin, Gennady; Elnitski, Laura

2015-01-01

The term CpG island methylator phenotype (CIMP) has been used to describe widespread DNA hypermethylation at CpG-rich genomic regions affecting clinically distinct subsets of cancer patients. Even though there have been numerous studies of CIMP in individual cancer types, a uniform analysis across tissues is still lacking. We analyze genome-wide patterns of CpG island hypermethylation in 5,253 solid epithelial tumors from 15 cancer types from TCGA and 23 cancer cell lines from ENCODE. We identify differentially methylated loci that define CIMP+ and CIMP- samples, and we use unsupervised clustering to provide a robust molecular stratification of tumor methylomes for 12 cancer types and all cancer cell lines. With a minimal set of 89 discriminative loci, we demonstrate accurate pan-cancer separation of the 12 CIMP+/- subpopulations, based on their average levels of methylation. Tumor samples in different CIMP subclasses show distinctive correlations with gene expression profiles and recurrence of somatic mutations, copy number variations, and epigenetic silencing. Enrichment analyses indicate shared canonical pathways and upstream regulators for CIMP-targeted regions across cancer types. Furthermore, genomic alterations showing consistent associations with CIMP+/- status include genes involved in DNA repair, chromatin remodeling genes, and several histone methyltransferases. Associations of CIMP status with specific clinical features, including overall survival in several cancer types, highlight the importance of the CIMP+/- designation for individual tumor evaluation and personalized medicine. We present a comprehensive computational study of CIMP that reveals pan-cancer commonalities and tissue-specific differences underlying concurrent hypermethylation of CpG islands across tumors. Our stratification of solid tumors and cancer cell lines based on CIMP status is data-driven and agnostic to tumor type by design, which protects against known biases that have hindered classic methods previously used to define CIMP. The results that we provide can be used to refine existing molecular subtypes of cancer into more homogeneously behaving subgroups, potentially leading to more uniform responses in clinical trials.

Autoimmune thyroiditis in children and adolescents with type 1 diabetes mellitus is associated with elevated IgG4 but not with low vitamin D.

PubMed

Demir, Korcan; Keskin, Mehmet; Kör, Yilmaz; Karaoğlan, Murat; Bülbül, Özlem Gümüştekin

2014-01-01

To assess levels of vitamin D and of immunoglobulin G subclasses in children and adolescents with type 1 Diabetes Mellitus with or without autoimmune thyroiditis. Among 213 patients with type 1 diabetes, the cases with thyroid-specific autoantibodies formed Group 1 [n=19, M/F: 7/12, median age 13 years (10.1-14.7)]. Nineteen age-, gender-, and diabetes duration-matched cases with type 1 diabetes without any other systemic disease were designated as controls [Group 2, M/F: 7/12, median age 12.9 years (10.5-14.9)]. Levels of thyroid hormones, vitamin D, total IgG and IgG subclasses, as well as IgG subclasses/total IgG ratios were similar between the groups. Five cases (26%) in Group 1 had IgG4 levels > + 2 SDS, whereas there were no such cases in Group 2 (p=0.046). These five patients had similar clinical features but higher median IgG4 levels and IgG4/Total IgG ratios compared to the subjects with IgG4 levels < + 2 SDS in Group 1 and Group 2. There was no difference of vitamin D levels between the groups. Only a small percentage of patients with type 1 diabetes also having autoimmune thyroiditis had elevated serum IgG4 levels, revealing the heterogeneity of autoimmune thyroiditis and existence of IgG4 thyroiditis in the pediatric age group. Total IgG, the other IgG subclasses, and vitamin D levels did not differ in patients with autoimmune thyroiditis and type 1 diabetes compared to those suffering only from type 1 diabetes.

Properties of Polycyclic Aromatic Hydrocarbons in the Northwest Photon Dominated Region of NGC 7023. I. PAH Size, Charge, Composition, and Structure Distribution

NASA Technical Reports Server (NTRS)

Boersma, C.; Bregman, Jesse; Allamandola, L. J

2013-01-01

Polycyclic aromatic hydrocarbon (PAH) emission in the Spitzer Infrared Spectrograph spectral map of the northwest photon dominated region (PDR) in NGC 7023 was analyzed exclusively using PAH spectra from the NASA Ames PAH IR Spectroscopic Database (www.astrochem.org/pahdb). The 5-15 micron spectrum at each pixel is fitted using a non-negative-least-squares fitting approach. The fits are of good quality, allowing decomposition of the PAH emission into four subclasses: size, charge, composition, and hydrogen adjacency (structure). Maps tracing PAH subclass distributions across the region paint a coherent astrophysical picture. Once past some 20 seconds of arc from HD 200775, the emission is dominated by the more stable, large, symmetric, compact PAH cations with smaller, neutral PAHs taking over along the lines-of-sight toward the more distant molecular cloud. The boundary between the PDR and the denser cloud material shows up as a distinct discontinuity in the breakdown maps. Noteworthy is the requirement for PANH cations to fit the bulk of the 6.2 and 11.0 micron features and the indication of PAH photo-dehydrogenation and fragmentation close to HD 200775. Decomposition of the spectral maps into "principal" subclass template spectra provides additional insight into the behavior of each subclass. However, the general applicability of this computationally more efficient approach is presently undetermined. This is the first time the spectra of individual PAHs are exclusively used to fit the 5-15 micron region and analyze the spatial behavior of the aromatic infrared bands, providing fundamental, new information about astronomical PAH subpopulations including their dependence on, and response to, changes in local conditions.

FAMILY ANALYSIS OF IMMUNOGLOBULIN CLASSES AND SUBCLASSES IN CHILDREN WITH AUTISTIC DISORDER

PubMed Central

Spiroski, Mirko; Trajkovski, Vladimir; Trajkov, Dejan; Petlichkovski, Aleksandar; Efinska-Mladenovska, Olivija; Hristomanova, Slavica; Djulejic, Eli; Paneva, Meri; Bozhikov, Jadranka

2009-01-01

Autistic disorder is a severe neurodevelopment disorder characterized by a triad of impairments in reciprocal social interaction, verbal and nonverbal communication, and a pattern of repetitive stereotyped activities, behaviours and interests. There are strong lines of evidence to suggest that the immune system plays an important role in the pathogenesis of autistic disorder. The aim of this study was to analyze quantitative plasma concentration of immunoglobulin classes, and subclasses in autistic patients and their families. The investigation was performed retrospectively in 50 persons with autistic disorder in the Republic of Macedonia. Infantile autistic disorder was diagnosed by DSM-IV and ICD-10 criteria. Plasma immunoglobulin classes (IgM, IgA, and IgG) and subclasses (IgG1, IgG2, IgG3, and IgG4) were determined using Nephelometer Analyzer BN-100. Multiple comparisons for the IgA variable have shown statistically significant differences between three pairs: male autistic from the fathers (p = 0,001), female autistic from the mothers (p = 0,008), as well as healthy sisters from the fathers (p = 0,011). Statistically significant differences found between three groups regarding autistic disorder (person with autistic disorder, father/mother of a person with autistic disorder, and brother/sister) independent of sex belongs to IgA, IgG2, and IgG3 variables. Multiple comparisons for the IgA variable have shown statistically significant differences between children with autistic disorder from the fathers and mothers (p < 0,001), and healthy brothers and sisters from the fathers and mothers (p < 0,001). Comparison between healthy children and children with autistic disorder from the same family should be tested for immunoglobulin classes and subclasses in order to avoid differences between generations. PMID:20001993

Family analysis of immunoglobulin classes and subclasses in children with autistic disorder.

PubMed

Spiroski, Mirko; Trajkovski, Vladimir; Trajkov, Dejan; Petlichkovski, Aleksandar; Efinska-Mladenovska, Olivija; Hristomanova, Slavica; Djulejic, Eli; Paneva, Meri; Bozhikov, Jadranka

2009-11-01

Autistic disorder is a severe neurodevelopment disorder characterized by a triad of impairments in reciprocal social interaction, verbal and nonverbal communication, and a pattern of repetitive stereotyped activities, behaviours and interests. There are strong lines of evidence to suggest that the immune system plays an important role in the pathogenesis of autistic disorder. The aim of this study was to analyze quantitative plasma concentration of immunoglobulin classes, and subclasses in autistic patients and their families. The investigation was performed retrospectively in 50 persons with autistic disorder in the Republic of Macedonia. Infantile autistic disorder was diagnosed by DSM-IV and ICD-10 criteria. Plasma immunoglobulin classes (IgM, IgA, and IgG) and subclasses (IgG1, IgG2, IgG3, and IgG4) were determined using Nephelometer Analyzer BN-100. Multiple comparisons for the IgA variable have shown statistically significant differences between three pairs: male autistic from the fathers (p = 0,001), female autistic from the mothers (p = 0,008), as well as healthy sisters from the fathers (p = 0,011). Statistically significant differences found between three groups regarding autistic disorder (person with autistic disorder, father/mother of a person with autistic disorder, and brother/sister) independent of sex belongs to IgA, IgG2, and IgG3 variables. Multiple comparisons for the IgA variable have shown statistically significant differences between children with autistic disorder from the fathers and mothers (p < 0,001), and healthy brothers and sisters from the fathers and mothers (p < 0,001). Comparison between healthy children and children with autistic disorder from the same family should be tested for immunoglobulin classes and subclasses in order to avoid differences between generations.

Spectral characterization of V-type asteroids - I. Space weathering effects and implications for V-type NEAs

NASA Astrophysics Data System (ADS)

Fulvio, Daniele; Perna, Davide; Ieva, Simone; Brunetto, Rosario; Kanuchova, Zuzana; Blanco, Carlo; Strazzulla, Giovanni; Dotto, Elisabetta

2016-01-01

Among main belt asteroids, V-types belonging to Vesta's dynamical family are known as `Vestoids' while those lying outside Vesta's family as `non-Vestoids'. V-types have also been found within the population of Near Earth Asteroids (NEAs). Several questions on Vesta, the V-types, and the Howardite-Eucrite-Diogenite meteorites are still unsolved, such as the genesis of each class/subclass, their evolution and mutual relationship, and the existence of other basaltic parent bodies. We present new NIR (0.8-2.4 μm) spectroscopic observations of seven non-Vestoids, carried out at the Telescopio Nazionale Galileo (TNG - INAF). We derived a number of spectral parameters (BI and BII centres, band separations, and BI slopes) and compared them with available spectra of V-types belonging to different subclasses (102 V-types in total), to highlight possible spectral differences useful to shed light on the questions mentioned above. We also considered the data from ion irradiation experiments performed on different samples of eucrites, simulating space weathering effects. Net discrepancies are seen for the BI slope distributions: NEAs show a distribution strongly different from all other V-type subclasses. Ion irradiation experiments induce strong effects on BI slope values and, as irradiation proceeds, the BI slope of eucrites quickly increases, changing the overall aspect of their VIS-NIR spectra (0.4-2.5 μm). Space weathering may explain the whole range of spectral slopes observed for all V-type subclasses. An exception is represented by NEAs, where moderate space weathering effects are evidenced. We propose that this is due to tidal perturbations exposing `fresh' unweathered surface grains during close encounters with the Earth, as previously found for Q-type NEAs.

Small high-density lipoprotein (HDL) subclasses are increased with decreased activity of HDL-associated phospholipase A₂ in subjects with prediabetes.

PubMed

Filippatos, Theodosios D; Rizos, Evangelos C; Tsimihodimos, Vasilios; Gazi, Irene F; Tselepis, Alexandros D; Elisaf, Moses S

2013-06-01

Alterations in high-density lipoprotein (HDL) subclass distribution, as well as in the activities of HDL-associated enzymes, have been associated with increased cardiovascular disease (CVD) risk. HDL subclass distribution and the activities of HDL-associated enzymes remain unknown in prediabetic patients, a condition also associated with increased CVD risk. The aim of the present study was to assess any differences in HDL subclass distribution (using polyacrylamide gel electrophoresis) and in activities of HDL-associated enzymes between prediabetic (impaired fasting glucose, IFG, n = 80) and non-prediabetic subjects (n = 105). Subjects with prediabetes had significantly increased waist circumference, blood pressure and triacylglycerol (TAG) levels compared with subjects with fasting glucose levels <100 mg/dL (all p < 0.05). The proportion of small HDL3 over HDL cholesterol (HDL-C) was significantly increased in prediabetic subjects compared with their controls (p < 0.05). The activity of the anti-atherogenic HDL-associated lipoprotein-associated phospholipase A₂ (HDL-LpPLA₂) was significantly lower in subjects with prediabetes (p < 0.05), whereas the activity of paraoxonase 1 (using both paraoxon and phenyl acetate as substrates) did not significantly differ between subjects with or without prediabetes. In a stepwise linear regression analysis, the proportion of small HDL3 over HDL-C concentration was independently associated with the presence of prediabetes and with total cholesterol and TAG concentration (positively), as well as with HDL-C levels (negatively). We also observed a trend of increased small dense low-density lipoprotein cholesterol levels in prediabetic subjects compared with their controls. Subjects with IFG exhibit increased proportion of small HDL3 particles combined with decreased activity of the anti-atherogenic HDL-LpPLA₂.

Human IgG subclass cross-species reactivity to mouse and cynomolgus monkey Fcγ receptors.

PubMed

Derebe, Mehabaw G; Nanjunda, Rupesh K; Gilliland, Gary L; Lacy, Eilyn R; Chiu, Mark L

2018-05-01

In therapeutic antibody discovery and early development, mice and cynomolgus monkey are used as animal models to assess toxicity, efficacy and other properties of candidate molecules. As more candidate antibodies are based on human immunoglobulin (IgG) subclasses, many strategies are pursued to simulate the human system in the test animal. However, translation rate from a successful preclinical trial to an approved drug is extremely low. This may partly be due to differences in interaction of human IgG based candidate molecules to endogenous Fcγ receptors of model animals in comparison to those of human Fcγ receptors. In this study, we compare binding characteristics of human IgG subclasses commonly used in drug development (IgG1, IgG2, IgG4) and their respective Fc silent versions (IgG1σ, IgG2σ, IgG4 PAA) to human, mouse, and cynomolgus monkey Fcγ receptors. To control interactions between Fab and Fc domains, the test IgGs all have the same variable region sequences. We found distinct variations of interaction of human IgG subclasses to model animal Fcγ receptors in comparison to their human counterparts. Particularly, cynomolgus monkey Fcγ receptors showed consistently tighter binding to human IgGs than human Fcγ receptors. Moreover, the presumably Fc silent human IgG4 PAA framework bound to cynomolgus monkey FcγRI with nanomolar affinity while only very weak binding was observed for the human FcγRI. Our results highlighted the need for a thorough in vitro affinity characterization of candidate IgGs against model animal Fcγ receptors and careful design of preclinical studies. Copyright © 2018. Published by Elsevier B.V.

Bacterial Community Structure and Physiological State within an Industrial Phenol Bioremediation System

PubMed Central

Whiteley, Andrew S.; Bailey, Mark J.

2000-01-01

The structure of bacterial populations in specific compartments of an operational industrial phenol remediation system was assessed to examine bacterial community diversity, distribution, and physiological state with respect to the remediation of phenolic polluted wastewater. Rapid community fingerprinting by PCR-based denaturing gradient gel electrophoresis (DGGE) of 16S rDNA indicated highly structured bacterial communities residing in all nine compartments of the treatment plant and not exclusively within the Vitox biological reactor. Whole-cell targeting by fluorescent in situ hybridization with specific oligonucleotides (directed to the α, β and γ subclasses of the class Proteobacteria [α-, β-, and γ-Proteobacteria, respectively], the Cytophaga-Flavobacterium group, and the Pseudomonas group) tended to mirror gross changes in bacterial community composition when compared with DGGE community fingerprinting. At the whole-cell level, the treatment compartments were numerically dominated by cells assigned to the Cytophaga-Flavobacterium group and to the γ-Proteobacteria. The α subclass Proteobacteria were of low relative abundance throughout the treatment system whilst the β subclass of the Proteobacteria exhibited local dominance in several of the processing compartments. Quantitative image analyses of cellular fluorescence was used as an indicator of physiological state within the populations probed with rDNA. For cells hybridized with EUB338, the mean fluorescence per cell decreased with increasing phenolic concentration, indicating the strong influence of the primary pollutant upon cellular rRNA content. The γ subclass of the Proteobacteria had a ribosome content which correlated positively with total phenolics and thiocyanate. While members of the Cytophaga-Flavobacterium group were numerically dominant in the processing system, their abundance and ribosome content data for individual populations did not correlate with any of the measured chemical parameters. The potential importance of the γ-Proteobacteria and the Cytophaga-Flavobacteria during this bioremediation process was highlighted. PMID:10831417

Impact of liver fat on the differential partitioning of hepatic triacylglycerol into VLDL subclasses on high and low sugar diets.

PubMed

Umpleby, A Margot; Shojaee-Moradie, Fariba; Fielding, Barbara; Li, Xuefei; Marino, Andrea; Alsini, Najlaa; Isherwood, Cheryl; Jackson, Nicola; Ahmad, Aryati; Stolinski, Michael; Lovegrove, Julie A; Johnsen, Sigurd; Jeewaka R Mendis, A S; Wright, John; Wilinska, Malgorzata E; Hovorka, Roman; Bell, Jimmy D; Thomas, E Louise; Frost, Gary S; Griffin, Bruce A

2017-11-01

Dietary sugars are linked to the development of non-alcoholic fatty liver disease (NAFLD) and dyslipidaemia, but it is unknown if NAFLD itself influences the effects of sugars on plasma lipoproteins. To study this further, men with NAFLD ( n = 11) and low liver fat 'controls' ( n = 14) were fed two iso-energetic diets, high or low in sugars (26% or 6% total energy) for 12 weeks, in a randomised, cross-over design. Fasting plasma lipid and lipoprotein kinetics were measured after each diet by stable isotope trace-labelling.There were significant differences in the production and catabolic rates of VLDL subclasses between men with NAFLD and controls, in response to the high and low sugar diets. Men with NAFLD had higher plasma concentrations of VLDL 1 -triacylglycerol (TAG) after the high ( P <0.02) and low sugar ( P <0.0002) diets, a lower VLDL 1 -TAG fractional catabolic rate after the high sugar diet ( P <0.01), and a higher VLDL 1 -TAG production rate after the low sugar diet ( P <0.01), relative to controls. An effect of the high sugar diet, was to channel hepatic TAG into a higher production of VLDL 1 -TAG ( P <0.02) in the controls, but in contrast, a higher production of VLDL 2 -TAG ( P <0.05) in NAFLD. These dietary effects on VLDL subclass kinetics could be explained, in part, by differences in the contribution of fatty acids from intra-hepatic stores, and de novo lipogenesis. The present study provides new evidence that liver fat accumulation leads to a differential partitioning of hepatic TAG into large and small VLDL subclasses, in response to high and low intakes of sugars. © 2017 The Author(s).

Association among Dietary Flavonoids, Flavonoid Subclasses and Ovarian Cancer Risk: A Meta-Analysis.

PubMed

Hua, Xiaoli; Yu, Lili; You, Ruxu; Yang, Yu; Liao, Jing; Chen, Dongsheng; Yu, Lixiu

2016-01-01

Previous studies have indicated that intake of dietary flavonoids or flavonoid subclasses is associated with the ovarian cancer risk, but presented controversial results. Therefore, we conducted a meta-analysis to derive a more precise estimation of these associations. We performed a search in PubMed, Google Scholar and ISI Web of Science from their inception to April 25, 2015 to select studies on the association among dietary flavonoids, flavonoid subclasses and ovarian cancer risk. The information was extracted by two independent authors. We assessed the heterogeneity, sensitivity, publication bias and quality of the articles. A random-effects model was used to calculate the pooled risk estimates. Five cohort studies and seven case-control studies were included in the final meta-analysis. We observed that intake of dietary flavonoids can decrease ovarian cancer risk, which was demonstrated by pooled RR (RR = 0.82, 95% CI = 0.68-0.98). In a subgroup analysis by flavonoid subtypes, the ovarian cancer risk was also decreased for isoflavones (RR = 0.67, 95% CI = 0.50-0.92) and flavonols (RR = 0.68, 95% CI = 0.58-0.80). While there was no compelling evidence that consumption of flavones (RR = 0.86, 95% CI = 0.71-1.03) could decrease ovarian cancer risk, which revealed part sources of heterogeneity. The sensitivity analysis indicated stable results, and no publication bias was observed based on the results of Funnel plot analysis and Egger's test (p = 0.26). This meta-analysis suggested that consumption of dietary flavonoids and subtypes (isoflavones, flavonols) has a protective effect against ovarian cancer with a reduced risk of ovarian cancer except for flavones consumption. Nevertheless, further investigations on a larger population covering more flavonoid subclasses are warranted.

Association among Dietary Flavonoids, Flavonoid Subclasses and Ovarian Cancer Risk: A Meta-Analysis

PubMed Central

You, Ruxu; Yang, Yu; Liao, Jing; Chen, Dongsheng; Yu, Lixiu

2016-01-01

Background Previous studies have indicated that intake of dietary flavonoids or flavonoid subclasses is associated with the ovarian cancer risk, but presented controversial results. Therefore, we conducted a meta-analysis to derive a more precise estimation of these associations. Methods We performed a search in PubMed, Google Scholar and ISI Web of Science from their inception to April 25, 2015 to select studies on the association among dietary flavonoids, flavonoid subclasses and ovarian cancer risk. The information was extracted by two independent authors. We assessed the heterogeneity, sensitivity, publication bias and quality of the articles. A random-effects model was used to calculate the pooled risk estimates. Results Five cohort studies and seven case-control studies were included in the final meta-analysis. We observed that intake of dietary flavonoids can decrease ovarian cancer risk, which was demonstrated by pooled RR (RR = 0.82, 95% CI = 0.68–0.98). In a subgroup analysis by flavonoid subtypes, the ovarian cancer risk was also decreased for isoflavones (RR = 0.67, 95% CI = 0.50–0.92) and flavonols (RR = 0.68, 95% CI = 0.58–0.80). While there was no compelling evidence that consumption of flavones (RR = 0.86, 95% CI = 0.71–1.03) could decrease ovarian cancer risk, which revealed part sources of heterogeneity. The sensitivity analysis indicated stable results, and no publication bias was observed based on the results of Funnel plot analysis and Egger’s test (p = 0.26). Conclusions This meta-analysis suggested that consumption of dietary flavonoids and subtypes (isoflavones, flavonols) has a protective effect against ovarian cancer with a reduced risk of ovarian cancer except for flavones consumption. Nevertheless, further investigations on a larger population covering more flavonoid subclasses are warranted. PMID:26960146

Properties of Polycyclic Aromatic Hydrocarbons in the Northwest Photon Dominated Region of NGC 7023. I. PAH Size, Charge, Composition, and Structure Distribution

NASA Astrophysics Data System (ADS)

Boersma, C.; Bregman, J. D.; Allamandola, L. J.

2013-06-01

Polycyclic aromatic hydrocarbon (PAH) emission in the Spitzer Infrared Spectrograph spectral map of the northwest photon dominated region (PDR) in NGC 7023 was analyzed exclusively using PAH spectra from the NASA Ames PAH IR Spectroscopic Database (www.astrochem.org/pahdb). The 5-15 μm spectrum at each pixel is fitted using a non-negative-least-squares fitting approach. The fits are of good quality, allowing decomposition of the PAH emission into four subclasses: size, charge, composition, and hydrogen adjacency (structure). Maps tracing PAH subclass distributions across the region paint a coherent astrophysical picture. Once past some 20 seconds of arc from HD 200775, the emission is dominated by the more stable, large, symmetric, compact PAH cations with smaller, neutral PAHs taking over along the lines-of-sight toward the more distant molecular cloud. The boundary between the PDR and the denser cloud material shows up as a distinct discontinuity in the breakdown maps. Noteworthy is the requirement for PANH cations to fit the bulk of the 6.2 and 11.0 μm features and the indication of PAH photo-dehydrogenation and fragmentation close to HD 200775. Decomposition of the spectral maps into "principal" subclass template spectra provides additional insight into the behavior of each subclass. However, the general applicability of this computationally more efficient approach is presently undetermined. This is the first time the spectra of individual PAHs are exclusively used to fit the 5-15 μm region and analyze the spatial behavior of the aromatic infrared bands, providing fundamental, new information about astronomical PAH subpopulations including their dependence on, and response to, changes in local conditions.

Dietary flavonoid intake and smoking-related cancer risk: a meta-analysis.

PubMed

Woo, Hae Dong; Kim, Jeongseon

2013-01-01

To systematically investigate the effects of dietary flavonoids and flavonoid subclasses on the risk of smoking-related cancer in observational studies. Summary estimates and corresponding standard errors were calculated using the multivariate-adjusted odds ratio (OR) or relative risk (RR) and 95% CI of selected studies and weighted by the inverse variance. A total of 35 studies, including 19 case-controls (9,525 cases and 15,835 controls) and 15 cohort studies (988,082 subjects and 8,161 cases), were retrieved for the meta-analysis. Total dietary flavonoids and most of the flavonoid subclasses were inversely associated with smoking-related cancer risk (OR: 0.82, 95% CI: 0.72-0.93). In subgroup analyses by cancer site, significant associations were observed in aerodigestive tract and lung cancers. Total dietary flavonoid intake was significantly associated with aerodigestive tract cancer risk (OR: 0.67, 95% CI: 0.54-0.83) marginally associated with lung cancer risk (OR: 0.84, 95% CI: 0.71-1.00). Subgroup analyses by smoking status showed significantly different results. The intake of total flavonoids, flavonols, flavones, and flavanones, as well as the flavonols quercetin and kaempferol was significantly associated with decreased risk of smoking-related cancer in smokers, whereas no association was observed in non-smokers, except for flavanones. In meta-analysis for the effect of subclasses of dietary flavonoids by cancer type, aerodigestive tract cancer was inversely associated with most flavonoid subclasses. The protective effects of flavonoids on smoking-related cancer risk varied across studies, but the overall results indicated that intake of dietary flavonoids, especially flavonols, was inversely associated with smoking-related cancer risk. The protective effects of flavonoids on smoking-related cancer risk were more prominent in smokers.

Dietary Flavonoid Intake and Smoking-Related Cancer Risk: A Meta-Analysis

PubMed Central

Woo, Hae Dong; Kim, Jeongseon

2013-01-01

Purpose To systematically investigate the effects of dietary flavonoids and flavonoid subclasses on the risk of smoking-related cancer in observational studies. Methods Summary estimates and corresponding standard errors were calculated using the multivariate-adjusted odds ratio (OR) or relative risk (RR) and 95% CI of selected studies and weighted by the inverse variance. Results A total of 35 studies, including 19 case-controls (9,525 cases and 15,835 controls) and 15 cohort studies (988,082 subjects and 8,161 cases), were retrieved for the meta-analysis. Total dietary flavonoids and most of the flavonoid subclasses were inversely associated with smoking-related cancer risk (OR: 0.82, 95% CI: 0.72-0.93). In subgroup analyses by cancer site, significant associations were observed in aerodigestive tract and lung cancers. Total dietary flavonoid intake was significantly associated with aerodigestive tract cancer risk (OR: 0.67, 95% CI: 0.54-0.83) marginally associated with lung cancer risk (OR: 0.84, 95% CI: 0.71-1.00). Subgroup analyses by smoking status showed significantly different results. The intake of total flavonoids, flavonols, flavones, and flavanones, as well as the flavonols quercetin and kaempferol was significantly associated with decreased risk of smoking-related cancer in smokers, whereas no association was observed in non-smokers, except for flavanones. In meta-analysis for the effect of subclasses of dietary flavonoids by cancer type, aerodigestive tract cancer was inversely associated with most flavonoid subclasses. Conclusion The protective effects of flavonoids on smoking-related cancer risk varied across studies, but the overall results indicated that intake of dietary flavonoids, especially flavonols, was inversely associated with smoking-related cancer risk. The protective effects of flavonoids on smoking-related cancer risk were more prominent in smokers. PMID:24069431

Effect of Pioglitazone on Cardio-Metabolic Risk in Patients with Obstructive Sleep Apnea

PubMed Central

Liu, Alice; Abbasi, Fahim; Kim, Sun H.; Ariel, Danit; Lamendola, Cindy; Cardell, James; Xu, Shiming; Patel, Shailja; Tomasso, Vanessa; Mojaddidi, Hafasa; Grove, Kaylene; Tsao, Philip S.; Kushida, Clete A.; Reaven, Gerald M.

2017-01-01

Prevalence of insulin resistance is increased in patients with obstructive sleep apnea (OSA). Since insulin resistance is an independent predictor of cardiovascular disease (CVD), this study was initiated to see if pioglitazone administration would improve insulin sensitivity, and thereby decrease risk of CVD in overweight/obese, nondiabetic, insulin-resistant patients with untreated OSA. Patients (n=30) were administered pioglitazone (45 mg/day) for 8 weeks, and measurements were made before and after intervention of insulin action (insulin-mediated glucose uptake by the insulin suppression test), C-reactive protein, lipid/lipoprotein profile, and gene expression profile of peri-umbilical subcutaneous fat tissue. Insulin sensitivity increased 31% (p<0.001) among pioglitazone-treated individuals, associated with a decrease in C-reactive protein concentration (p≤ 0.001), a decrease in plasma triglyceride and increase in high-density lipoprotein cholesterol concentrations (p≤ 0.001), accompanied by significant changes in apolipoprotein A1 and B concentrations and lipoprotein subclasses known to decrease CVD risk. In addition, subcutaneous adipose tissue gene expression profile showed a 1.6-fold (p<0.01) increase in GLUT4 expression, as well as decreased expression in 5 of 9 inflammatory genes (p<0.05). In conclusion, enhanced insulin sensitivity can significantly decrease multiple cardio-metabolic risk factors in patients with untreated OSA, consistent with the view that coexisting insulin resistance plays an important role in the association between OSA and increased risk of CVD. PMID:28219664

Numeric invariants from multidimensional persistence

DOE Office of Scientific and Technical Information (OSTI.GOV)

Skryzalin, Jacek; Carlsson, Gunnar

2017-05-19

In this paper, we analyze the space of multidimensional persistence modules from the perspectives of algebraic geometry. We first build a moduli space of a certain subclass of easily analyzed multidimensional persistence modules, which we construct specifically to capture much of the information which can be gained by using multidimensional persistence over one-dimensional persistence. We argue that the global sections of this space provide interesting numeric invariants when evaluated against our subclass of multidimensional persistence modules. Lastly, we extend these global sections to the space of all multidimensional persistence modules and discuss how the resulting numeric invariants might be usedmore » to study data.« less

Psychotropic polypharmacy in Australia, 2006 to 2015: a descriptive cohort study.

PubMed

Brett, Jonathan; Daniels, Benjamin; Karanges, Emily A; Buckley, Nicholas A; Schneider, Carl; Nassir, Atheer; McLachlan, Andrew J; Pearson, Sallie-Anne

2017-11-01

To describe psychotropic polypharmacy in Australia between 2006 and 2015. We used pharmaceutical claims from a national 10% sample of people with complete dispensing histories to estimate the annual prevalence of the combined use (overlap of >60 days exposure) of ≥2 psychotropics overall and within the same class or subclass (class and subclass polypharmacy). We also estimated the proportion of polypharmacy episodes involving one, two, three and four or more unique prescribers. The prevalence of class polypharmacy between 2006 and 2015 in people dispensed specific psychotropic classes was 5.9-7.3% for antipsychotics, 2.1-3.7% for antidepressants and 4.3-2.9% for benzodiazepines. The prevalence of antipsychotic polypharmacy was higher than expected given the prevalence of antipsychotic exposure and combinations of sedating agents were notably common. Overall, 26.7% of polypharmacy episodes involved multiple prescribers but having multiple prescribers occurred more frequently for class and subclass polypharmacy and people with four or more concomitant psychotropics. Psychotropic polypharmacy is common, despite limited evidence of risks and benefits. Increases in polypharmacy with multiple prescribers may be due to poor communication with patients and between health care professionals. © 2017 The British Pharmacological Society.

Abnormal serum IgG subclass pattern in children with Down's syndrome.

PubMed

Annerén, G; Magnusson, C G; Lilja, G; Nordvall, S L

1992-05-01

Susceptibility to infections is a well known feature of Down's syndrome. The possible relation between this predisposition and the serum concentrations of the IgG subclasses was studied in 38 children with Down's syndrome aged 1-12 years. An age matched group of 50 healthy children served as controls. The serum concentrations of IgG1 and IgG3 were significantly raised among children with Down's syndrome in all three age groups studied (that is 1-2.5, 4-8, and 9-12 years). The serum concentrations of IgG2 were normal in the first two groups but significantly reduced in the third age group. In contrast, the concentrations of IgG4 among children with Down's syndrome were significantly reduced in all three age groups. Moreover, among the children with Down's syndrome aged 4-12 years 68% (15/22) had IgG4 concentrations below 2 SDs of the geometrical mean of the controls. The results may partially explain the proneness of children with Down's syndrome to infections with encapsulated bacteria. Although the underlying cause of these abnormalities is unknown, IgG subclass determination seems relevant in the clinical evaluation of children with Down's syndrome.

Abnormal serum IgG subclass pattern in children with Down's syndrome.

PubMed Central

Annerén, G; Magnusson, C G; Lilja, G; Nordvall, S L

1992-01-01

Susceptibility to infections is a well known feature of Down's syndrome. The possible relation between this predisposition and the serum concentrations of the IgG subclasses was studied in 38 children with Down's syndrome aged 1-12 years. An age matched group of 50 healthy children served as controls. The serum concentrations of IgG1 and IgG3 were significantly raised among children with Down's syndrome in all three age groups studied (that is 1-2.5, 4-8, and 9-12 years). The serum concentrations of IgG2 were normal in the first two groups but significantly reduced in the third age group. In contrast, the concentrations of IgG4 among children with Down's syndrome were significantly reduced in all three age groups. Moreover, among the children with Down's syndrome aged 4-12 years 68% (15/22) had IgG4 concentrations below 2 SDs of the geometrical mean of the controls. The results may partially explain the proneness of children with Down's syndrome to infections with encapsulated bacteria. Although the underlying cause of these abnormalities is unknown, IgG subclass determination seems relevant in the clinical evaluation of children with Down's syndrome. PMID:1534650

Seroconversion to filarial antigens in Australian defence force personnel in Timor-Leste.

PubMed

Frances, Stephen P; Baade, Lisa M; Kubofcik, Joseph; Nutman, Thomas B; Melrose, Wayne D; McCarthy, James S; Nissen, Michael D

2008-04-01

To investigate whether Australian soldiers were exposed to filarial parasites that cause lymphatic filariasis during a 6-month deployment to Timor-Leste, antifilarial antibody levels were measured in 907 soldiers using an enzyme linked immunosorbent assay (ELISA). Initial testing using Dirofilaria immitis antigen demonstrated that 49 of 907 (5.4%) soldiers developed antifilarial antibodies of the IgG1 subclass after deployment, whereas 1 of 944 (0.1%) seroconverted to the IgG4 subclass. When a sub sample of 88 D. immitis-reactive sera was subject to testing with an antifilarial antibody test using Brugia malayi antigen, 46 had elevated IgG antibodies, whereas 5 had elevated antibodies of the IgG4 subclass. A total of 24 soldiers seroconverted to B. malayi, as measured by parasite-specific IgG, whereas 1 seroconverted to IgG4. The relatively low number of seroconversions indicates a low but measurable risk of exposure to human filarial parasites among Australian soldiers deployed to Timor-Leste. However, to reduce the risk of exposure to these parasites, soldiers deploying to endemic areas should practice strict adherence to personal protective measures against mosquito bites.

Nesting in an Object Oriented Language is NOT for the Birds

NASA Astrophysics Data System (ADS)

Buhr, P. A.; Zarnke, C. R.

The notion of nested blocks has come into disfavour or has been ignored in recent program language design. Many of the current object oriented programming languages use subclassing as the sole mechanism to establish relationships between classes and have no general notion of nesting. We argue that nesting (and, more generally, hierarchical organization) is a powerful mechanism that provides facilities that are not otherwise possible in a class based programming language. We agree that traditional block structure and its associated nesting have severe problems, and we suggest several extensions to the notion of blocks and block structure that indirectly make nesting a useful and powerful mechanism, particularly in an object oriented programming system. The main extension is to allow references to definitions from outside of the containing block, thereby making the contained definitions available in a larger scope. References are made using either the name of the containing entity or an instance of the containing entity. The extensions suggest a way to organize the programming environment for a large, multi-user system. These facilities are not available with subclassing, and subclassing provides facilities not available by nesting; hence, an object oriented language can benefit by providing nesting as well.

A natural human monoclonal antibody targeting Staphylococcus Protein A protects against Staphylococcus aureus bacteremia

PubMed Central

Varshney, Avanish K.; Sunley, Kevin M.; Bowling, Rodney A.; Kwan, Tzu-Yu; Mays, Heather R.; Rambhadran, Anu; Zhang, Yanfeng; Martin, Rebecca L.; Cavalier, Michael C.; Simard, John

2018-01-01

Staphylococcus aureus can cause devastating and life-threatening infections. With the increase in multidrug resistant strains, novel therapies are needed. Limited success with active and passive immunization strategies have been attributed to S. aureus immune evasion. Here, we report on a monoclonal antibody, 514G3, that circumvents a key S. aureus evasion mechanism by targeting the cell wall moiety Protein A (SpA). SpA tightly binds most subclasses of immunoglobulins via their Fc region, neutralizing effector function. The organism can thus shield itself with a protective coat of serum antibodies and render humoral immunity ineffective. The present antibody reactivity was derived from an individual with natural anti-SpA antibody titers. The monoclonal antibody is of an IgG3 subclass, which differs critically from other immunoglobulin subclasses since its Fc is not bound by SpA. Moreover, it targets a unique epitope on SpA that allows it to bind in the presence of serum antibodies. Consequently, the antibody opsonizes S. aureus and maintains effector function to enable natural immune mediated clearance. The data presented here provide evidence that 514G3 antibody is able to successfully rescue mice from S. aureus mediated bacteremia. PMID:29364906

Influence of pH on heat-induced aggregation and degradation of therapeutic monoclonal antibodies.

PubMed

Ishikawa, Tomoyoshi; Ito, Takahiko; Endo, Ryosuke; Nakagawa, Keiko; Sawa, Eiji; Wakamatsu, Kaori

2010-01-01

Monoclonal antibodies are widely used for the treatment of various diseases, and because therapeutic monoclonal antibodies are stored in an aqueous solution or in a lyophilized state, the preparation of a stabilizing formulation that prevents their deterioration (degradation and aggregation) is crucial. Given the structural similarities of the immunoglobulin G (IgG) framework regions and a diversity of only four subclasses, we aimed to find common conditions that stabilize many different antibodies. In this study, we analyzed the effect of pH (the most critical factor in establishing a stable formulation) on human monoclonal antibodies from subclasses IgG1, IgG2, and IgG4, all of which have been utilized in antibody therapeutics. We found that human IgGs are stable with minimal heat-induced degradation and aggregation at pH 5.0-5.5 irrespective of their subclass. We also found that IgG1 is more susceptible to fragmentation, whereas IgG4 is more susceptible to aggregation. This basic information emphasizing the influence of pH on IgG stability should facilitate the optimization of formulation conditions tailored to individual antibodies for specific uses.

Global stability of an age-structure epidemic model with imperfect vaccination and relapse

NASA Astrophysics Data System (ADS)

Cao, Bin; Huo, Hai-Feng; Xiang, Hong

2017-11-01

A new age-structured epidemic model with imperfect vaccination and relapse is proposed. The total population of our model is partitioned into five subclasses: susceptible class S, vaccinated class V, exposed class E, infectious class I and removed class R. Age-structures are equipped with in exposed and recovered classes. Furthermore, imperfect vaccination is also introduced in our model. The basic reproduction number R0 is defined and proved as a threshold parameter of the model. Asymptotic smoothness of solutions and uniform persistence of the system are showed via reformulating the system as a system of Volterra integral equation. Furthermore, by constructing proper Volterra-type Lyapunov functional we get when R0 < 1, the disease-free equilibrium is globally asymptotically stable. When R0 > 1, the endemic equilibrium is globally stable. Our results show that to increase the efficiency of vaccination and reduce influence of relapse are vital essential for controlling epidemic.

Mass loss from interacting close binary systems

NASA Technical Reports Server (NTRS)

Plavec, M. J.

1981-01-01

The three well-defined classes of evolved binary systems that show evidence of present and/or past mass loss are the cataclysmic variables, the Algols, and Wolf-Rayet stars. It is thought that the transformation of supergiant binary systems into the very short-period cataclysmic variables must have been a complex process. The new evidence that has recently been obtained from the far ultraviolet spectra that a certain subclass of the Algols (the Serpentids) are undergoing fairly rapid evolution is discussed. It is thought probable that the remarkable mass outflow observed in them is connected with a strong wind powered by accretion. The origin of the circumbinary clouds or flat disks that probably surround many strongly interacting binaries is not clear. Attention is also given to binary systems with hot white dwarf or subdwarf components, such as the symbiotic objects and the BQ stars; it is noted that in them both components may be prone to an enhanced stellar wind.

The rise and fall of a human recombination hot spot.

PubMed

Jeffreys, Alec J; Neumann, Rita

2009-05-01

Human meiotic crossovers mainly cluster into narrow hot spots that profoundly influence patterns of haplotype diversity and that may also affect genome instability and sequence evolution. Hot spots also seem to be ephemeral, but processes of hot-spot activation and their subsequent evolutionary dynamics remain unknown. We now analyze the life cycle of a recombination hot spot. Sperm typing revealed a polymorphic hot spot that was activated in cis by a single base change, providing evidence for a primary sequence determinant necessary, though not sufficient, to activate recombination. This activating mutation occurred roughly 70,000 y ago and has persisted to the present, most likely fortuitously through genetic drift despite its systematic elimination by biased gene conversion. Nonetheless, this self-destructive conversion will eventually lead to hot-spot extinction. These findings define a subclass of highly transient hot spots and highlight the importance of understanding hot-spot turnover and how it influences haplotype diversity.

Identification of distinct telencephalic progenitor pools for neuronal diversity in the amygdala

PubMed Central

Hirata, Tsutomu; Li, Peijun; Lanuza, Guillermo M.; Cocas, Laura A.; Huntsman, Molly M.; Corbin, Joshua G.

2009-01-01

Development of the amygdala, a central structure of the limbic system, remains poorly understood. Using mouse as a model, our studies reveal that two spatially distinct and early specified telencephalic progenitor pools marked by the homeodomain transcription factor Dbx1 are major sources of neuronal cell diversity in the mature amygdala. We find that Dbx1+ cells of the ventral pallium (VP) generate excitatory neurons of the basolateral complex and cortical amygdala nuclei. Moreover, Dbx1-derived cells comprise a novel migratory stream that emanates from the preoptic area (POA), a ventral telencephalic domain adjacent to the diencephalic border. The Dbx1+ POA-derived population migrates specifically to the amygdala, and as defined by both immunochemical and electrophysiological criteria, generates a unique subclass of inhibitory neurons in the medial amygdala nucleus. Thus, this POA-derived population represents a novel progenitor pool dedicated to the limbic system. PMID:19136974

Identification of distinct telencephalic progenitor pools for neuronal diversity in the amygdala.

PubMed

Hirata, Tsutomu; Li, Peijun; Lanuza, Guillermo M; Cocas, Laura A; Huntsman, Molly M; Corbin, Joshua G

2009-02-01

The development of the amygdala, a central structure of the limbic system, remains poorly understood. We found that two spatially distinct and early-specified telencephalic progenitor pools marked by the homeodomain transcription factor Dbx1 are major sources of neuronal cell diversity in the mature mouse amygdala. We found that Dbx1-positive cells of the ventral pallium generate the excitatory neurons of the basolateral complex and cortical amygdala nuclei. Moreover, Dbx1-derived cells comprise a previously unknown migratory stream that emanates from the preoptic area (POA), a ventral telencephalic domain adjacent to the diencephalic border. The Dbx1-positive, POA-derived population migrated specifically to the amygdala and, as defined by both immunochemical and electrophysiological criteria, generated a unique subclass of inhibitory neurons in the medial amygdala nucleus. Thus, this POA-derived population represents a previously unknown progenitor pool dedicated to the limbic system.

Tractable Pareto Optimization of Temporal Preferences

NASA Technical Reports Server (NTRS)

Morris, Robert; Morris, Paul; Khatib, Lina; Venable, Brent

2003-01-01

This paper focuses on temporal constraint problems where the objective is to optimize a set of local preferences for when events occur. In previous work, a subclass of these problems has been formalized as a generalization of Temporal CSPs, and a tractable strategy for optimization has been proposed, where global optimality is defined as maximizing the minimum of the component preference values. This criterion for optimality, which we call 'Weakest Link Optimization' (WLO), is known to have limited practical usefulness because solutions are compared only on the basis of their worst value; thus, there is no requirement to improve the other values. To address this limitation, we introduce a new algorithm that re-applies WLO iteratively in a way that leads to improvement of all the values. We show the value of this strategy by proving that, with suitable preference functions, the resulting solutions are Pareto Optimal.

Searching for chemical classes among metal-poor stars using medium-resolution spectroscopy

NASA Astrophysics Data System (ADS)

Cruz, Monique A.; Cogo-Moreira, Hugo; Rossi, Silvia

2018-04-01

Astronomy is in the era of large spectroscopy surveys, with the spectra of hundreds of thousands of stars in the Galaxy being collected. Although most of these surveys have low or medium resolution, which makes precise abundance measurements not possible, there is still important information to be extracted from the available data. Our aim is to identify chemically distinct classes among metal-poor stars, observed by the Sloan Digital Sky Survey, using line indices. The present work focused on carbon-enhanced metal-poor (CEMP) stars and their subclasses. We applied the latent profile analysis technique to line indices for carbon, barium, iron and europium, in order to separate the sample into classes with similar chemical signatures. This technique provides not only the number of possible groups but also the probability of each object to belong to each class. The method was able to distinguish at least two classes among the observed sample, with one of them being probable CEMP stars enriched in s-process elements. However, it was not able to separate CEMP-no stars from the rest of the sample. Latent profile analysis is a powerful model-based tool to be used in the identification of patterns in astrophysics. Our tests show the potential of the technique for the attainment of additional chemical information from `poor' data.

Prevalence of dyslipidemia among Iranian patients with idiopathic tinnitus

PubMed Central

M-Shirazi, Minoo; Farhadi, Mohammad; Jalessi, Maryam; Kamrava, Seyyed-Kamran; Behzadi, Ashkan Heshmatzade; Arami, Behin

2011-01-01

BACKGROUND: Tinnitus is a sense of sound perception in absence of an external source which can affect life quality. Different conditions may lead to tinnitus including metabolic disorders such as dyslipidemia. The aim of this study was to investigate the prevalence of dyslipidemia among Iranian patients with idiopathic tinnitus. METHODS: This was a cross-sectional study in which prevalence of dyslipidemia in fasting state and its subclasses were assessed in 1043 tinnitus patients aged 12-90 years who referred to Rasool Akram Hospital, Tehran, Iran, 2006-2009. Data was summarized by SPSS software version 17 and one sample t-test and Chi-Square test were applied to analyze the results. P less than 0.05 were considered significant. RESULTS: The most prevalent type of dyslipidemia was hypercholesterolemia with the frequency of 14.4% followed by low HDL-C with the frequency of 12.8%. Mean of total cholesterol, HDL-C, LDL-C and triglyceride levels in all patients were not greater than general population. CONCLUSIONS: Based on the results of the present study, there might be no need to check the serum lipid profile in tinnitus patients. We recommend further studies to assess both fasting and postprandial serum lipid profile in patients with idiopathic tinnitus. Simultaneous investigation of their dietary intake is also suggested. PMID:22279456

Prevalence of dyslipidemia among Iranian patients with idiopathic tinnitus.

PubMed

M-Shirazi, Minoo; Farhadi, Mohammad; Jalessi, Maryam; Kamrava, Seyyed-Kamran; Behzadi, Ashkan Heshmatzade; Arami, Behin

2011-07-01

Tinnitus is a sense of sound perception in absence of an external source which can affect life quality. Different conditions may lead to tinnitus including metabolic disorders such as dyslipidemia. The aim of this study was to investigate the prevalence of dyslipidemia among Iranian patients with idiopathic tinnitus. This was a cross-sectional study in which prevalence of dyslipidemia in fasting state and its subclasses were assessed in 1043 tinnitus patients aged 12-90 years who referred to Rasool Akram Hospital, Tehran, Iran, 2006-2009. Data was summarized by SPSS software version 17 and one sample t-test and Chi-Square test were applied to analyze the results. P less than 0.05 were considered significant. The most prevalent type of dyslipidemia was hypercholesterolemia with the frequency of 14.4% followed by low HDL-C with the frequency of 12.8%. Mean of total cholesterol, HDL-C, LDL-C and triglyceride levels in all patients were not greater than general population. Based on the results of the present study, there might be no need to check the serum lipid profile in tinnitus patients. We recommend further studies to assess both fasting and postprandial serum lipid profile in patients with idiopathic tinnitus. Simultaneous investigation of their dietary intake is also suggested.

Alkaloids Profiling of Fumaria capreolata by Analytical Platforms Based on the Hyphenation of Gas Chromatography and Liquid Chromatography with Quadrupole-Time-of-Flight Mass Spectrometry.

PubMed

Contreras, María Del Mar; Bribi, Noureddine; Gómez-Caravaca, Ana María; Gálvez, Julio; Segura-Carretero, Antonio

2017-01-01

Two analytical platforms, gas chromatography (GC) coupled to quadrupole-time-of-flight (QTOF) mass spectrometry (MS) and reversed-phase ultrahigh performance liquid chromatography (UHPLC) coupled to diode array (DAD) and QTOF detection, were applied in order to study the alkaloid profile of Fumaria capreolata . The use of these mass analyzers enabled tentatively identifying the alkaloids by matching their accurate mass signals and suggested molecular formulae with those previously reported in libraries and databases. Moreover, the proposed structures were corroborated by studying their fragmentation pattern obtained by both platforms. In this way, 8 and 26 isoquinoline alkaloids were characterized using GC-QTOF-MS and RP-UHPLC-DAD-QTOF-MS, respectively, and they belonged to the following subclasses: protoberberine, protopine, aporphine, benzophenanthridine, spirobenzylisoquinoline, morphinandienone, and benzylisoquinoline. Moreover, the latter analytical method was selected to determine at 280 nm the concentration of protopine (9.6 ± 0.7 mg/g), a potential active compound of the extract. In conclusion, although GC-MS has been commonly used for the analysis of this type of phytochemicals, RP-UHPLC-DAD-QTOF-MS provided essential complementary information. This analytical method can be applied for the quality control of phytopharmaceuticals containing Fumaria extracts currently found in the market.

Alkaloids Profiling of Fumaria capreolata by Analytical Platforms Based on the Hyphenation of Gas Chromatography and Liquid Chromatography with Quadrupole-Time-of-Flight Mass Spectrometry

PubMed Central

Bribi, Noureddine; Gómez-Caravaca, Ana María

2017-01-01

Two analytical platforms, gas chromatography (GC) coupled to quadrupole-time-of-flight (QTOF) mass spectrometry (MS) and reversed-phase ultrahigh performance liquid chromatography (UHPLC) coupled to diode array (DAD) and QTOF detection, were applied in order to study the alkaloid profile of Fumaria capreolata. The use of these mass analyzers enabled tentatively identifying the alkaloids by matching their accurate mass signals and suggested molecular formulae with those previously reported in libraries and databases. Moreover, the proposed structures were corroborated by studying their fragmentation pattern obtained by both platforms. In this way, 8 and 26 isoquinoline alkaloids were characterized using GC-QTOF-MS and RP-UHPLC-DAD-QTOF-MS, respectively, and they belonged to the following subclasses: protoberberine, protopine, aporphine, benzophenanthridine, spirobenzylisoquinoline, morphinandienone, and benzylisoquinoline. Moreover, the latter analytical method was selected to determine at 280 nm the concentration of protopine (9.6 ± 0.7 mg/g), a potential active compound of the extract. In conclusion, although GC-MS has been commonly used for the analysis of this type of phytochemicals, RP-UHPLC-DAD-QTOF-MS provided essential complementary information. This analytical method can be applied for the quality control of phytopharmaceuticals containing Fumaria extracts currently found in the market. PMID:29348751

Metabolic signatures of birthweight in 18 288 adolescents and adults

PubMed Central

Würtz, Peter; Wang, Qin; Niironen, Marjo; Tynkkynen, Tuulia; Tiainen, Mika; Drenos, Fotios; Kangas, Antti J; Soininen, Pasi; Skilton, Michael R; Heikkilä, Kauko; Pouta, Anneli; Kähönen, Mika; Lehtimäki, Terho; Rose, Richard J; Kajantie, Eero; Perola, Markus; Kaprio, Jaakko; Eriksson, Johan G; Raitakari, Olli T; Lawlor, Debbie A; Davey Smith, George; Järvelin, Marjo-Riitta; Ala-Korpela, Mika; Auro, Kirsi

2016-01-01

Background: Lower birthweight is associated with increased susceptibility to cardiometabolic diseases in adulthood, but the underlying molecular pathways are incompletely understood. We examined associations of birthweight with a comprehensive metabolic profile measured in adolescents and adults. Methods: High-throughput nuclear magnetic resonance metabolomics and biochemical assays were used to quantify 87 circulating metabolic measures in seven cohorts from Finland and the UK, comprising altogether 18 288 individuals (mean age 26 years, range 15–75). Metabolic associations with birthweight were assessed by linear regression models adjusted for sex, gestational age and age at blood sampling. The metabolic associations with birthweight were compared with the corresponding associations with adult body mass index (BMI). Results: Lower birthweight adjusted for gestational age was adversely associated with cardiometabolic biomarkers, including lipoprotein subclasses, fatty acids, amino acids and markers of inflammation and impaired liver function (P < 0.0015 for 46 measures). Associations were consistent across cohorts with different ages at metabolic profiling, but the magnitudes were weak. The pattern of metabolic deviations associated with lower birthweight resembled the metabolic signature of higher adult BMI (R2 = 0.77) assessed at the same time as the metabolic profiling. The resemblance indicated that 1 kg lower birthweight is associated with similar metabolic aberrations as caused by 0.92 units higher BMI in adulthood. Conclusions: Lower birthweight adjusted for gestational age is associated with adverse biomarker aberrations across multiple metabolic pathways. Coherent metabolic signatures between lower birthweight and higher adult adiposity suggest that shared molecular pathways may potentially underpin the metabolic deviations. However, the magnitudes of metabolic associations with birthweight are modest in comparison to the effects of adiposity, implying that birthweight is only a weak indicator of the metabolic risk profile in adulthood. PMID:27892411

Metabolic profiling of gestational diabetes in obese women during pregnancy.

PubMed

White, Sara L; Pasupathy, Dharmintra; Sattar, Naveed; Nelson, Scott M; Lawlor, Debbie A; Briley, Annette L; Seed, Paul T; Welsh, Paul; Poston, Lucilla

2017-10-01

Antenatal obesity and associated gestational diabetes (GDM) are increasing worldwide. While pre-existing insulin resistance is implicated in GDM in obese women, the responsible metabolic pathways remain poorly described. Our aim was to compare metabolic profiles in blood of obese pregnant women with and without GDM 10 weeks prior to and at the time of diagnosis by OGTT. We investigated 646 women, of whom 198 developed GDM, in this prospective cohort study, a secondary analysis of UK Pregnancies Better Eating and Activity Trial (UPBEAT), a multicentre randomised controlled trial of a complex lifestyle intervention in obese pregnant women. Multivariate regression analyses adjusted for multiple testing, and accounting for appropriate confounders including study intervention, were performed to compare obese women with GDM with obese non-GDM women. We measured 163 analytes in serum, plasma or whole blood, including 147 from a targeted NMR metabolome, at time point 1 (mean gestational age 17 weeks 0 days) and time point 2 (mean gestational age 27 weeks 5 days, at time of OGTT) and compared them between groups. Multiple significant differences were observed in women who developed GDM compared with women without GDM (false discovery rate corrected p values <0.05). Most were evident prior to diagnosis. Women with GDM demonstrated raised lipids and lipoprotein constituents in VLDL subclasses, greater triacylglycerol enrichment across lipoprotein particles, higher branched-chain and aromatic amino acids and different fatty acid, ketone body, adipokine, liver and inflammatory marker profiles compared with those without GDM. Among obese pregnant women, differences in metabolic profile, including exaggerated dyslipidaemia, are evident at least 10 weeks prior to a diagnosis of GDM in the late second trimester.

High-Energy Spectral and Temporal Characteristics of GRO J1008-57

NASA Astrophysics Data System (ADS)

Shrader, C. R.; Sutaria, F. K.; Singh, K. P.; Macomb, D. J.

1999-02-01

A transient X-ray source, GRO J1008-57, was discovered by the Burst and Transient Source Experiment (BATSE) on board the Compton Gamma Ray Observatory (CGRO) in 1993 July. It reached a maximum intensity of about 1.4 times that of the Crab, in the 20-60 keV energy band. Pulsations in the X-ray intensity were detected at a period of 93.5 s. It has subsequently been determined to be a member of the Be star subclass of X-ray transients. In addition to BATSE, GRO J1008-57 was observed during its outburst by several pointed high-energy experiments: ROSAT, ASCA, and CGRO/OSSE. These nonsimultaneous but contemporaneous observations took place near and shortly after the peak of the outburst light curve. We report for the first time on a combined analysis of the CGRO and ASCA data sets. We have attempted to model the broadband high-energy continuum distribution and phase-resolved spectra. The broadband, phase-averaged continuum is well approximated by a power law with an exponential cutoff. Evidence for 6.4 keV line emission due to Fe is presented based on our spectral analysis. The energy dependence of the pulse profiles is examined in order to determine the energy at which the low-energy double-peaked profile detected by ASCA evolves into single-peaked pulse profile detected by BATSE. We discuss the implications of this pulse profile for the magnetic field and beam distribution for GRO J1008-57. Analysis of the BATSE and Rossi X-Ray Timing Explorer/ASM flux histories suggests that Porbital~135 days. We further suggest that a transient disk is likely to form during episodes of outbursts.

Diagnosis and classification of hematologic malignancies on the basis of genetics

PubMed Central

2017-01-01

Genomic analysis has greatly influenced the diagnosis and clinical management of patients affected by diverse forms of hematologic malignancies. Here, we review how genetic alterations define subclasses of patients with acute leukemias, myelodysplastic syndromes (MDS), myeloproliferative neoplasms (MPNs), non-Hodgkin lymphomas, and classical Hodgkin lymphoma. These include new subtypes of acute myeloid leukemia defined by mutations in RUNX1 or BCR-ABL1 translocations as well as a constellation of somatic structural DNA alterations in acute lymphoblastic leukemia. Among patients with MDS, detection of mutations in SF3B1 define a subgroup of patients with the ring sideroblast form of MDS and a favorable prognosis. For patients with MPNs, detection of the BCR-ABL1 fusion delineates chronic myeloid leukemia from classic BCR-ABL1− MPNs, which are largely defined by mutations in JAK2, CALR, or MPL. In the B-cell lymphomas, detection of characteristic rearrangements involving MYC in Burkitt lymphoma, BCL2 in follicular lymphoma, and MYC/BCL2/BCL6 in high-grade B-cell lymphomas are essential for diagnosis. In T-cell lymphomas, anaplastic large-cell lymphoma is defined by mutually exclusive rearrangements of ALK, DUSP22/IRF4, and TP63. Genetic alterations affecting TP53 and the mutational status of the immunoglobulin heavy-chain variable region are important in clinical management of chronic lymphocytic leukemia. Additionally, detection of BRAFV600E mutations is helpful in the diagnosis of classical hairy cell leukemia and a number of histiocytic neoplasms. Numerous additional examples provided here demonstrate how clinical evaluation of genomic alterations have refined classification of myeloid neoplasms and major forms of lymphomas arising from B, T, or natural killer cells. PMID:28600336

Integration of the social environment in a mobility ontology for people with motor disabilities.

PubMed

Gharebaghi, Amin; Mostafavi, Mir-Abolfazl; Edwards, Geoffrey; Fougeyrollas, Patrick; Gamache, Stéphanie; Grenier, Yan

2017-07-07

Our contemporary understanding of disability is rooted in the idea that disability is the product of human-environment interaction processes. People may be functionally limited, but this becomes a disability only when they engage with their immediate social and physical environments. Any attempt to address issues of mobility in relation to people with disabilities should be grounded in an ontology that encompasses this understanding. The objective of this study is to provide a methodology to integrate the social and physical environments in the development of a mobility ontology for people with motor disabilities (PWMD). We propose to create subclasses of concepts based on a Nature-Development distinction rather than creating separate social and physical subclasses. This allows the relationships between social and physical elements to be modelled in a more compact and efficient way by specifying them locally within each entity, and better accommodates the complexities of the human-environment interaction as well. Based on this approach, an ontology for mobility of PWMD considering four main elements - the social and physical environmental factors, human factors, life habits related to mobility and possible goals of mobility - is presented. We demonstrate that employing the Nature-Development perspective facilitates the process of developing useful ontologies, especially for defining the relationships between the social and physical parts of the environment. This is a fundamental issue for modelling the interaction between humans and their social and physical environments for a broad range of applications, including the development of geospatial assistive technologies for navigation of PWMD. Implications for rehabilitation The proposed perspective may actually have much broader interests beyond the issue of disability - much of the interesting dynamics in city development arises from the interaction between human-developed components - the built environment and its associated entities - and natural or organic components. The proposed approach facilitates the process of developing useful ontologies, especially for defining the relationships between the social and physical parts of the environment. This is a fundamental issue for modeling the interaction between human -specially people with disabilities -and his social and physical environments in a broad range of domains and applications, such as Geographic Information Systems and the development of geospatial assistive technologies for navigation of people with disabilities, respectively.

Accumulate-Repeat-Accumulate-Accumulate Codes

NASA Technical Reports Server (NTRS)

Divsalar, Dariush; Dolinar, Samuel; Thorpe, Jeremy

2007-01-01

Accumulate-repeat-accumulate-accumulate (ARAA) codes have been proposed, inspired by the recently proposed accumulate-repeat-accumulate (ARA) codes. These are error-correcting codes suitable for use in a variety of wireless data-communication systems that include noisy channels. ARAA codes can be regarded as serial turbolike codes or as a subclass of low-density parity-check (LDPC) codes, and, like ARA codes they have projected graph or protograph representations; these characteristics make it possible to design high-speed iterative decoders that utilize belief-propagation algorithms. The objective in proposing ARAA codes as a subclass of ARA codes was to enhance the error-floor performance of ARA codes while maintaining simple encoding structures and low maximum variable node degree.

The binding of human and guinea-pig IgG subclasses to homologous macrophage and monocyte Fc receptors.

PubMed Central

Alexander, M D; Andrews, J A; Leslie, R G; Wood, N J

1978-01-01

Guinea-pig IgG2 and IgT1 bind to contiguous Fc receptors on homologous peritoneal macrophages. Equilibrium association constants determined for the binding of human IgG subclasses to homologous peripheral blood monocytes show that the order of binding is IgG1 greater than IgG3 greater than IgG4 greater than IgG2. Direct binding and rosette assay techniques independently established that both guinea-pig IgG2 and human IgG bind to homologous macrophage-monocyte Fc receptors through a site present in whole Fc (CH2. CH3)2, but absent in pFc' subfragments (CH3)2. PMID:680795

Superbounce and loop quantum ekpyrotic cosmologies from modified gravity: F(R) , F(G) and F(T) theories

NASA Astrophysics Data System (ADS)

Odintsov, S. D.; Oikonomou, V. K.; Saridakis, Emmanuel N.

2015-12-01

We investigate the realization of two bouncing paradigms, namely of the superbounce and the loop quantum cosmological ekpyrosis, in the framework of various modified gravities. In particular, we focus on the F(R) , F(G) and F(T) gravities, and we reconstruct their specific subclasses which lead to such universe evolutions. These subclasses constitute from power laws, polynomials, or hypergeometric ansatzes, which can be approximated by power laws. The qualitative similarity of the different effective gravities which realize the above two bouncing cosmologies, indicates that a universality might be lying behind the bounce. Finally, performing a linear perturbation analysis, we show that the obtained solutions are conditionally or fully stable.

A novel structural tree for wrap-proteins, a subclass of (α+β)-proteins.

PubMed

Boshkova, Eugenia A; Gordeev, Alexey B; Efimov, Alexander V

2014-01-01

In this paper, a novel structural subclass of (α+β)-proteins is presented. A characteristic feature of these proteins and domains is that they consist of strongly twisted and coiled β-sheets wrapped around one or two α-helices, so they are referred to here as wrap-proteins. It is shown that overall folds of the wrap-proteins can be obtained by stepwise addition of α-helices and/or β-strands to the strongly twisted and coiled β-hairpin taken as the starting structure in modeling. As a result of modeling, a structural tree for the wrap-proteins was constructed that includes 201 folds of which 49 occur in known nonhomologous proteins.

Chemical identification of the mammalian oxytocin in a holocephalian fish, the ratfish (Hydrolagus colliei).

PubMed

Michel, G; Chauvet, J; Chauvet, M T; Clarke, C; Bern, H; Acher, R

1993-11-01

The neurohypophysial hormones of the ratfish (Hydrolagus colliei), a species belonging to the subclass Holocephali of cartilaginous fishes, have been investigated. An oxytocin-like hormone has been isolated from acetone-desiccated pituitary glands by using successively molecular sieving and high-pressure liquid chromatography. The peptide has been identified as oxytocin by coelution with synthetic oxytocin in HPLC, amino acid sequencing, mass spectrometry, and C-terminal sequencing through carboxypeptidase Y. Vasotocin may be present in a very small amount. Cartilaginous fishes appear to display a great diversity in their oxytocin-like hormones since five different peptides have been identified in rays and sharks that belong to the second subclass Selachii.

Subclass specificities of rabbit antibodies to human antidextran.

PubMed

Outschoorn, I M

1983-03-01

Rabbits were immunized with purified antidextran containing IgG2. Half of the animals were treated with commercial human IgG intravenously to induce tolerance. The antisera were absorbed and/or eluted from IgG-Sepharose columns and the antibodies tested with a panel of at least eight human myeloma proteins of the four IgG subclasses, both kappa and lambda types. All animals produced mainly anti-IgG2 or IgG4, sometimes intechanged between these maxima or between kappa and lambda types over a series of bleedings. Absorption with IgG2 and/or IgG4 myeloma proteins resulted in sera or antibody preparations specific for the IgG1 or IgG3 subclasses, and the amount of those antibodies also varied between bleedings from the same animal. It may be concluded that anti-IgG2 and anti-IgG4 syntheses are related in a complementary manner or are equally likely to be produced in a response to IgG2; while IgG1 and IgG3 are also interrelated, but with an inverse relationship to IgG2 and IgG4. Alternatively anti-IgG2 and anti-IgG4 antibodies could be highly cross-reactive, and so could anti-IgG1 and anti-IgG3 antibodies.

Subclass specificities of rabbit antibodies to human antidextran.

PubMed Central

Outschoorn, I M

1983-01-01

Rabbits were immunized with purified antidextran containing IgG2. Half of the animals were treated with commercial human IgG intravenously to induce tolerance. The antisera were absorbed and/or eluted from IgG-Sepharose columns and the antibodies tested with a panel of at least eight human myeloma proteins of the four IgG subclasses, both kappa and lambda types. All animals produced mainly anti-IgG2 or IgG4, sometimes intechanged between these maxima or between kappa and lambda types over a series of bleedings. Absorption with IgG2 and/or IgG4 myeloma proteins resulted in sera or antibody preparations specific for the IgG1 or IgG3 subclasses, and the amount of those antibodies also varied between bleedings from the same animal. It may be concluded that anti-IgG2 and anti-IgG4 syntheses are related in a complementary manner or are equally likely to be produced in a response to IgG2; while IgG1 and IgG3 are also interrelated, but with an inverse relationship to IgG2 and IgG4. Alternatively anti-IgG2 and anti-IgG4 antibodies could be highly cross-reactive, and so could anti-IgG1 and anti-IgG3 antibodies. PMID:6186599

Flavonoids, Flavonoid Subclasses, and Esophageal Cancer Risk: A Meta-Analysis of Epidemiologic Studies.

PubMed

Cui, Lingling; Liu, Xinxin; Tian, Yalan; Xie, Chen; Li, Qianwen; Cui, Han; Sun, Changqing

2016-06-08

Flavonoids have been suggested to play a chemopreventive role in carcinogenesis. However, the epidemiologic studies assessing dietary intake of flavonoids and esophageal cancer risk have yielded inconsistent results. This study was designed to examine the association between flavonoids, each flavonoid subclass, and the risk of esophageal cancer with a meta-analysis approach. We searched for all relevant studies with a prospective cohort or case-control study design published from January 1990 to April 2016, using PUBMED, EMBASE, and Web of Science. Pooled odds ratios (ORs) were calculated using fixed or random-effect models. In total, seven articles including 2629 cases and 481,193 non-cases were selected for the meta-analysis. Comparing the highest-intake patients with the lowest-intake patients for total flavonoids and for each flavonoid subclass, we found that anthocyanidins (OR = 0.60, 95% CI: 0.49-0.74), flavanones (OR = 0.65, 95% CI: 0.49-0.86), and flavones (OR = 0.78, 95% CI 0.64-0.95) were inversely associated with the risk of esophageal cancer. However, total flavonoids showed marginal association with esophageal cancer risk (OR = 0.78, 95% CI: 0.59-1.04). In conclusion, our study suggested that dietary intake of total flavonoids, anthocyanidins, flavanones, and flavones might reduce the risk of esophageal cancer.

Natural Language Processing Based Instrument for Classification of Free Text Medical Records

PubMed Central

2016-01-01

According to the Ministry of Labor, Health and Social Affairs of Georgia a new health management system has to be introduced in the nearest future. In this context arises the problem of structuring and classifying documents containing all the history of medical services provided. The present work introduces the instrument for classification of medical records based on the Georgian language. It is the first attempt of such classification of the Georgian language based medical records. On the whole 24.855 examination records have been studied. The documents were classified into three main groups (ultrasonography, endoscopy, and X-ray) and 13 subgroups using two well-known methods: Support Vector Machine (SVM) and K-Nearest Neighbor (KNN). The results obtained demonstrated that both machine learning methods performed successfully, with a little supremacy of SVM. In the process of classification a “shrink” method, based on features selection, was introduced and applied. At the first stage of classification the results of the “shrink” case were better; however, on the second stage of classification into subclasses 23% of all documents could not be linked to only one definite individual subclass (liver or binary system) due to common features characterizing these subclasses. The overall results of the study were successful. PMID:27668260

Innate Lymphoid Cells (ILCs) as Mediators of Inflammation, Release of Cytokines and Lytic Molecules

PubMed Central

Elemam, Noha Mousaad

2017-01-01

Innate lymphoid cells (ILCs) are an emerging group of immune cells that provide the first line of defense against various pathogens as well as contributing to tissue repair and inflammation. ILCs have been classically divided into three subgroups based on their cytokine secretion and transcription factor profiles. ILC nomenclature is analogous to that of T helper cells. Group 1 ILCs composed of natural killer (NK) cells as well as IFN-γ secreting ILC1s. ILC2s have the capability to produce TH2 cytokines while ILC3s and lymphoid tissue inducer (LTis) are subsets of cells that are able to secrete IL-17 and/or IL-22. A recent subset of ILC known as ILC4 was discovered, and the cells of this subset were designated as NK17/NK1 due to their release of IL-17 and IFN-γ. In this review, we sought to explain the subclasses of ILCs and their roles as mediators of lytic enzymes and inflammation. PMID:29232860

Innate Lymphoid Cells (ILCs) as Mediators of Inflammation, Release of Cytokines and Lytic Molecules.

PubMed

Elemam, Noha Mousaad; Hannawi, Suad; Maghazachi, Azzam A

2017-12-10

Innate lymphoid cells (ILCs) are an emerging group of immune cells that provide the first line of defense against various pathogens as well as contributing to tissue repair and inflammation. ILCs have been classically divided into three subgroups based on their cytokine secretion and transcription factor profiles. ILC nomenclature is analogous to that of T helper cells. Group 1 ILCs composed of natural killer (NK) cells as well as IFN-γ secreting ILC1s. ILC2s have the capability to produce T H 2 cytokines while ILC3s and lymphoid tissue inducer (LTis) are subsets of cells that are able to secrete IL-17 and/or IL-22. A recent subset of ILC known as ILC4 was discovered, and the cells of this subset were designated as NK17/NK1 due to their release of IL-17 and IFN-γ. In this review, we sought to explain the subclasses of ILCs and their roles as mediators of lytic enzymes and inflammation.

A spectrophotometric study of RW Trianguli

NASA Astrophysics Data System (ADS)

Groot, P. J.; Rutten, R. G. M.; van Paradijs, J.

2004-04-01

On the basis of spectrophotometric observations we reconstruct the accretion disk of the eclipsing novalike cataclysmic variable RW Tri in the wavelength region 3600-7000 Å. We find a radial temperature profile that is, on average, consistent with that expected on the basis of the theory of optically thick, steady state accretion disks and infer a mass-accretion rate in RW Tri of ˜10-8 M⊙ yr-1. The line emission is dominated by two areas: one around the hot-spot region and one near the white dwarf. Both emission regions have appreciable vertical extension, and seem to be decoupled from the velocity field in the disk. In our observations RW Tri shows a number of features that are characteristic of the SW Sex sub-class of novalike stars. The appearance of a novalike system as a UX UMa/RW Tri or SW Sex star seems to be mainly governed by the mass-transfer rate from the secondary at the time of observation.

Role of dihydropyridinic calcium channel blockers in the management of hypertension.

PubMed

Coca, Antonio; Mazón, Pilar; Aranda, Pedro; Redón, Josep; Divisón, Juan Antonio; Martínez, Javier; Calvo, Carlos; Galcerán, Josep María; Barrios, Vivencio; Roca-Cusachs I Coll, Alexandre

2013-01-01

Dihydropyridinic calcium channel blockers are a subclass of antihypertensive drugs with growing significance in the therapeutic armamentarium. Early studies in the 1990s had aroused certain fears with regard to the safety of the first drugs from this class, since they had a fast onset of action and a short half-life, and thus they were associated with reflex adrenergic activation. New molecules with long half-lives and high lipophilia have shown safety and efficacy in the control of blood pressure, as well as in the reduction of several end points related to hypertension. Moreover, these new molecules, which block special subtypes of calcium channel receptors, provide drugs not only with an action profile that goes beyond the antihypertensive effect, but also with a lower rate of side effects. Therefore, in the light of new studies that include calcium channel blockers alone or in combination, these agents will probably be used even more extensively for the management of hypertension in the following years.

Aberrant activity of NKL homeobox gene NKX3-2 in a T-ALL subset

PubMed Central

Meyer, Corinna; Kaufmann, Maren; Zaborski, Margarete; MacLeod, Roderick A. F.; Drexler, Hans G.

2018-01-01

T-cell acute lymphoblastic leukemia (T-ALL) is a hematopoietic malignancy originating from T-cell progenitors in which differentiation is blocked at early stages. Physiological expression of specific NKL homeobox genes obeys a hematopoietic NKL-code implicated in the process of lymphopoiesis while in differentiated T-cells these genes are silenced. We propose that this developmental expression pattern underlies the observation that NKL homeobox genes are the most ubiquitous group of transcription factors deregulated in T-ALL, including TLX1, TLX3, NKX2-5 and NKX3-1. Here, we describe a novel member of the NKL homeobox gene subclass, NKX3-2 (BAPX1), which is aberrantly activated in 18% of pediatric T-ALL patients analyzed while being normally expressed in developing spleen. Identification of NKX3-2 expression in T-ALL cell line CCRF-CEM qualified these cells to model its deregulation and function in a leukemic context. Genomic and chromosomal analyses demonstrated normal configuration of the NKX3-2 locus at chromosome 4p15, thus excluding cytogenetic dysregulation. Comparative expression profiling analysis of NKX3-2 patient data revealed deregulated activity of BMP- and MAPK-signalling. These candidate pathways were experimentally confirmed to mediate aberrant NKX3-2 expression. We also show that homeobox gene SIX6, plus MIR17HG and GATA3 are downstream targets of NKX3-2 and plausibly contribute to the pathogenesis of this malignancy by suppressing T-cell differentiation. Finally, NKL homeobox gene NKX2-5 was activated by NKX3-2 in CCRF-CEM and by FOXG1 in PEER, representing mutually inhibitory activators of this translocated oncogene. Together, our findings reveal a novel oncogenic NKL homeobox gene subclass member which is aberrantly expressed in a large subset of T-ALL patients and participates in a deregulated gene network likely to arise in developing spleen. PMID:29746601

Non-amidated and amidated members of the C-type allatostatin (AST-C) family are differentially distributed in the stomatogastric nervous system of the American lobster, Homarus americanus.

PubMed

Christie, Andrew E; Miller, Alexandra; Fernandez, Rebecca; Dickinson, Evyn S; Jordan, Audrey; Kohn, Jessica; Youn, Mina C; Dickinson, Patsy S

2018-01-13

The crustacean stomatogastric nervous system (STNS) is a well-known model for investigating neuropeptidergic control of rhythmic behavior. Among the peptides known to modulate the STNS are the C-type allatostatins (AST-Cs). In the lobster, Homarus americanus, three AST-Cs are known. Two of these, pQIRYHQCYFNPISCF (AST-C I) and GNGDGRLYWRCYFNAVSCF (AST-C III), have non-amidated C-termini, while the third, SYWKQCAFNAVSCFamide (AST-C II), is C-terminally amidated. Here, antibodies were generated against one of the non-amidated peptides (AST-C I) and against the amidated isoform (AST-C II). Specificity tests show that the AST-C I antibody cross-reacts with both AST-C I and AST-C III, but not AST-C II; the AST-C II antibody does not cross-react with either non-amidated peptide. Wholemount immunohistochemistry shows that both subclasses (non-amidated and amidated) of AST-C are distributed throughout the lobster STNS. Specifically, the antibody that cross-reacts with the two non-amidated peptides labels neuropil in the CoGs and the stomatogastric ganglion (STG), axons in the superior esophageal (son) and stomatogastric (stn) nerves, and ~ 14 somata in each commissural ganglion (CoG). The AST-C II-specific antibody labels neuropil in the CoGs, STG and at the junction of the sons and stn, axons in the sons and stn, ~ 42 somata in each CoG, and two somata in the STG. Double immunolabeling shows that, except for one soma in each CoG, the non-amidated and amidated peptides are present in distinct sets of neuronal profiles. The differential distributions of the two AST-C subclasses suggest that the two peptide groups are likely to serve different modulatory roles in the lobster STNS.

Aberrant activity of NKL homeobox gene NKX3-2 in a T-ALL subset.

PubMed

Nagel, Stefan; Meyer, Corinna; Kaufmann, Maren; Zaborski, Margarete; MacLeod, Roderick A F; Drexler, Hans G

2018-01-01

T-cell acute lymphoblastic leukemia (T-ALL) is a hematopoietic malignancy originating from T-cell progenitors in which differentiation is blocked at early stages. Physiological expression of specific NKL homeobox genes obeys a hematopoietic NKL-code implicated in the process of lymphopoiesis while in differentiated T-cells these genes are silenced. We propose that this developmental expression pattern underlies the observation that NKL homeobox genes are the most ubiquitous group of transcription factors deregulated in T-ALL, including TLX1, TLX3, NKX2-5 and NKX3-1. Here, we describe a novel member of the NKL homeobox gene subclass, NKX3-2 (BAPX1), which is aberrantly activated in 18% of pediatric T-ALL patients analyzed while being normally expressed in developing spleen. Identification of NKX3-2 expression in T-ALL cell line CCRF-CEM qualified these cells to model its deregulation and function in a leukemic context. Genomic and chromosomal analyses demonstrated normal configuration of the NKX3-2 locus at chromosome 4p15, thus excluding cytogenetic dysregulation. Comparative expression profiling analysis of NKX3-2 patient data revealed deregulated activity of BMP- and MAPK-signalling. These candidate pathways were experimentally confirmed to mediate aberrant NKX3-2 expression. We also show that homeobox gene SIX6, plus MIR17HG and GATA3 are downstream targets of NKX3-2 and plausibly contribute to the pathogenesis of this malignancy by suppressing T-cell differentiation. Finally, NKL homeobox gene NKX2-5 was activated by NKX3-2 in CCRF-CEM and by FOXG1 in PEER, representing mutually inhibitory activators of this translocated oncogene. Together, our findings reveal a novel oncogenic NKL homeobox gene subclass member which is aberrantly expressed in a large subset of T-ALL patients and participates in a deregulated gene network likely to arise in developing spleen.

IgG abnormality in narcolepsy and idiopathic hypersomnia.

PubMed

Tanaka, Susumu; Honda, Makoto

2010-03-05

A close association between narcolepsy and the Human Leukocyte Antigen (HLA)-DQB1*0602 allele suggests the involvement of the immune system, or possibly an autoimmune process. We investigated serum IgG levels in narcolepsy. We measured the serum total IgG levels in 159 Japanese narcolepsy-cataplexy patients positive for the HLA-DQB1*0602 allele, 28 idiopathic hypersomnia patients with long sleep time, and 123 healthy controls (the HLA-DQB1*0602 allele present in 45 subjects). The serum levels of each IgG subclass were subsequently measured. The distribution of serum IgG was significantly different among healthy controls negative for the HLA-DQB1*0602 allele (11.66+/-3.55 mg/ml), healthy controls positive for the HLA-DQB1*0602 allele (11.45+/-3.43), narcolepsy patients (9.67+/-3.38), and idiopathic hypersomnia patients (13.81+/-3.80). None of the following clinical variables, age, disease duration, Epworth Sleepiness Scale, smoking habit and BMI at the time of blood sampling, were associated with IgG levels in narcolepsy or idiopathic hypersomnia. Furthermore we found the decrease in IgG1 and IgG2 levels, stable expression of IgG3, and the increase in the proportion of IgG4 in narcolepsy patients with abnormally low IgG levels. The increase in the proportion of IgG4 levels was also found in narcolepsy patients with normal serum total IgG levels. Idiopathic hypersomnia patients showed a different pattern of IgG subclass distribution with high IgG3 and IgG4 level, low IgG2 level, and IgG1/IgG2 imbalance. Our study is the first to determine IgG abnormalities in narcolepsy and idiopathic hypersomnia by measuring the serum IgG levels in a large number of hypersomnia patients. The observed IgG abnormalities indicate humoral immune alterations in narcolepsy and idiopathic hypersomnia. Different IgG profiles suggest immunological differences between narcolepsy and idiopathic hypersomnia.

Treatment with exenatide once weekly or twice daily for 30 weeks is associated with changes in several cardiovascular risk markers

PubMed Central

Chiquette, Elaine; Toth, Peter P; Ramirez, Gilbert; Cobble, Michael; Chilton, Robert

2012-01-01

Background Dyslipidemia and type 2 diabetes are two of the most significant risk factors for the development of cardiovascular disease. Measurement of lipoprotein subclasses provides important information about derangements in lipid metabolism and helps refine cardiovascular risk assessment. Exenatide, a glucagon-like peptide 1 receptor agonist, improved glycemic control, obesity, hypertension, and dyslipidemia in patients with type 2 diabetes in clinical trials. Methods In the DURATION-1 trial, patients with type 2 diabetes were treated with exenatide once weekly or twice daily for 30 weeks. This post hoc analysis evaluated the impact of exenatide on lipoprotein subclasses in 211 DURATION-1 patients using vertical auto profile methodology and the Statistical Package for the Social Sciences general linear model adjusted for glycosylated hemoglobin (HbA1c) and weight. Results Baseline lipids and high sensitivity C-reactive protein were normal overall based on the standard lipid panel. Once-weekly exenatide reduced apolipoprotein B and the apolipoprotein B to apolipoprotein A1 ratio (P < 0.05), independent of glycemic improvement and weight loss. A significant shift in lipoprotein pattern away from small, dense low-density lipoprotein-4 cholesterol was also observed (P < 0.05). Exenatide once weekly increased high-density lipoprotein-2 cholesterol, even after adjustment for changes in HbA1c and weight (P < 0.05). Triglycerides, very low-density lipoprotein cholesterol, and high sensitivity C-reactive protein were reduced with both the once-weekly and twice-daily exenatide regimens (P < 0.05). Conclusion In this post hoc analysis, exenatide significantly improved a number of cardiovascular risk markers. Continuous exenatide exposure with exenatide once weekly elicited a greater response than did immediate-release exenatide twice daily, generally independent of glycemic improvement and weight loss. Thus, in addition to improving glycemic control, exenatide induced favorable changes in lipid and lipoprotein metabolism and decreased systemic inflammation. PMID:23166441

Molecular Mechanisms of Aldehyde Toxicity: A Chemical Perspective

PubMed Central

2015-01-01

Aldehydes are electrophilic compounds to which humans are pervasively exposed. Despite a significant health risk due to exposure, the mechanisms of aldehyde toxicity are poorly understood. This ambiguity is likely due to the structural diversity of aldehyde derivatives and corresponding differences in chemical reactions and biological targets. To gain mechanistic insight, we have used parameters based on the hard and soft, acids and bases (HSAB) theory to profile the different aldehyde subclasses with respect to electronic character (softness, hardness), electrophilic reactivity (electrophilic index), and biological nucleophilic targets. Our analyses indicate that short chain aldehydes and longer chain saturated alkanals are hard electrophiles that cause toxicity by forming adducts with hard biological nucleophiles, e.g., primary nitrogen groups on lysine residues. In contrast, α,β-unsaturated carbonyl derivatives, alkenals, and the α-oxoaldehydes are soft electrophiles that preferentially react with soft nucleophilic thiolate groups on cysteine residues. The aldehydes can therefore be grouped into subclasses according to common electronic characteristics (softness/hardness) and molecular mechanisms of toxicity. As we will discuss, the toxic potencies of these subgroups are generally related to corresponding electrophilicities. For some aldehydes, however, predictions of toxicity based on electrophilicity are less accurate due to inherent physicochemical variables that limit target accessibility, e.g., steric hindrance and solubility. The unsaturated aldehydes are also members of the conjugated type-2 alkene chemical class that includes α,β-unsaturated amide, ketone, and ester derivatives. Type-2 alkenes are electrophiles of varying softness and electrophilicity that share a common mechanism of toxicity. Therefore, exposure to an environmental mixture of unsaturated carbonyl derivatives could cause “type-2 alkene toxicity” through additive interactions. Finally, we propose that environmentally derived aldehydes can accelerate diseases by interacting with endogenous aldehydes generated during oxidative stress. This review provides a basis for understanding aldehyde mechanisms and environmental toxicity through the context of electronic structure, electrophilicity, and nucleophile target selectivity. PMID:24911545

Molecular diversity of mesophilic and thermophilic bacteria in a membrane bioreactor determined by fluorescent in situ hybridization with mxaF- and rRNA-targeted probes.

PubMed

Dias, João Carlos T; Silva, Cláudio M; Mounteer, Ann H; Passos, Flavia M L; Linardi, Valter R

2003-01-01

An evaluation of the efficiency of treatment of kraft mill foul condensates in a membrane bioreactor was carried out in the laboratory. Efficiency and rate of methanol removal were quantified at operating temperatures of 35, 45 and 55 degrees C. The structure of the bacterial community present in the reactor biomass at the different operating temperatures was evaluated by in situ hybridization of the biomass samples with fluorescently-labelled probes (FISH) targeting the Eubacteria, the alpha, beta and gamma subclasses of the Proteobacteria, the low G + C content Gram-positive bacteria (Bacillus spp.), while community function was evaluated by in situ hybridization with a methanol dehydrogenase gene (mxaF) probe. Methanol removal efficiency decreased from 99.4 to 92%, and removal rate from 2.69 mg MeOH/l x min to 2.49 mg MeOH/l x min when the operating temperature was increased from 35 to 55 degrees C. This decrease in methanol removal was accompanied by a decrease (from 58% to 42%) in the relative proportion of cells that hybridized with the mxaF probe. The relative proportion of Bacillus spp. increased from 5 to 20% while the proportion of members of the alpha subclass of Proteobacteria decreased from 16% to 6% when the bioreactor operating temperature was raised from 35 to 55 degrees C. The relative proportions of bacteria belonging to the beta (22-25%) and gamma (18-20%) subclasses of the Proteobacteria remained relatively constant regardless of operating temperature. Proteobacteria (alpha, beta and gamma subclasses) and Bacillus spp. represented 61, 67 and 71% of the Eubacteria in the biomass sampled at 35, 45 and 55 degrees C, respectively. The FISH technique was shown to be an efficient method for detection of both structural and functional changes in the bacterial communities that could be related to efficiency of methanol removal in a membrane bioreactor operating at different temperatures.

Advantages and Disadvantages of Adult Spinal Deformity Surgery and Its Impact on Health-Related Quality of Life.

PubMed

Yoshida, Go; Boissiere, Louis; Larrieu, Daniel; Bourghli, Anouar; Vital, Jean Marc; Gille, Olivier; Pointillart, Vincent; Challier, Vincent; Mariey, Remi; Pellisé, Ferran; Vila-Casademunt, Alba; Perez-Grueso, Francisco Javier Sánchez; Alanay, Ahmet; Acaroglu, Emre; Kleinstück, Frank; Obeid, Ibrahim

2017-03-15

Prospective multicenter study of adult spinal deformity (ASD) surgery. To clarify the effect of ASD surgery on each health-related quality of life (HRQOL) subclass/domain. For patients with ASD, surgery offers superior radiological and HRQOL outcomes compared with nonoperative care. HRQOL may, however, be affected by surgical advantages related to corrective effects, yielding adequate spinopelvic alignment and stability or disadvantages because of long segment fusion. The study included 170 consecutive patients with ASD from a multicenter database with more than 2-year follow-up period. We analyzed each HRQOL domain/subclass (short form-36 items, Oswestry Disability Index, Scoliosis Research Society-22 [SRS-22] questionnaire), and radiographic parameters preoperatively and at 1 and 2 years postoperatively. We divided the patients into two groups each based on lowest instrumented vertebra (LIV; above L5 or S1 to ilium) or surgeon-determined preoperative pathology (idiopathic or degenerative). Improvement rate (%) was calculated as follows: 100 × |pre.-post.|/preoperative points (%) (+, advantages; -, disadvantages). The scores of all short form-36 items and SRS-22 subclasses improved at 1 and 2 years after surgery, regardless of LIV location and preoperative pathology. Personal care and lifting in Oswestry Disability Index were, however, not improved after 1 year. These disadvantages were correlated to sagittal modifiers of SRS-Schwab classification similar to other HRQOL. The degree of personal care disadvantage mainly depended on LIV location and preoperative pathology. Although personal care improved after 2 years postoperatively, no noticeable improvements in lifting were recorded. HRQOL subclass analysis indicated two disadvantages of ASD surgery, which were correlated to sagittal radiographic measures. Fusion to the sacrum or ilium greatly restricted the ability to stretch or bend, leading to limited daily activities for at least 1 year postoperatively, although this effect may subside after another year. Consequently, spinal surgeons should note the effect of surgical treatment on each HRQOL domain and counsel patients about the implications of surgery. 4.

HLA class I antibodies trigger increased adherence of monocytes to endothelial cells by eliciting an increase in endothelial P-selectin and, depending on subclass, by engaging FcγRs1

PubMed Central

Valenzuela, Nicole M; Mulder, Arend; Reed, Elaine F

2013-01-01

Antibody-mediated rejection of solid organ transplants is characterized by intragraft macrophages. It is incompletely understood how donor specific antibody binding to graft endothelium promotes monocyte adhesion, and what, if any, contribution is made by the Fc region of the antibody. We investigated the mechanisms underlying monocyte recruitment by HLA class I antibody-activated endothelium. We used a panel of murine monoclonal antibodies of different subclasses to crosslink HLA I on human aortic, venous and microvascular endothelial cells, and measured the binding of human monocytic cell lines and peripheral blood monocytes. Both anti-HLA I murine IgG1 and mIgG2a induced endothelial P-selectin, which was required for monocyte adhesion to endothelium irrespective of subclass. Mouse IgG2a but not mIgG1 could bind human FcγRs. Accordingly, HLA I mIgG2a but not mIgG1 treatment of endothelial cells significantly augmented recruitment, predominantly through FcγRI, and, to a lesser extent, FcγRIIa. Moreover, HLA I mIgG2a promoted firm adhesion of monocytes to ICAM-1 through Mac-1, which may explain the prominence of monocytes during antibody mediated rejection. We confirmed these observations using human HLA allele specific monoclonal antibodies and IgG purified from transplant patient sera. HLA I antibodies universally elicit endothelial exocytosis leading to monocyte adherence, implying that P-selectin is a putative therapeutic target to prevent macrophage infiltration during antibody-mediated rejection. Importantly, the subclass of donor specific antibody may influence its pathogenesis. These results imply that hIgG1 and hIgG3 should have a greater capacity to trigger monocyte infiltration into the graft than IgG2 or IgG4 due to enhancement by FcγR interactions. PMID:23690477

HLA class I antibodies trigger increased adherence of monocytes to endothelial cells by eliciting an increase in endothelial P-selectin and, depending on subclass, by engaging FcγRs.

PubMed

Valenzuela, Nicole M; Mulder, Arend; Reed, Elaine F

2013-06-15

Ab-mediated rejection (AMR) of solid organ transplants is characterized by intragraft macrophages. It is incompletely understood how donor-specific Ab binding to graft endothelium promotes monocyte adhesion, and what, if any, contribution is made by the Fc region of the Ab. We investigated the mechanisms underlying monocyte recruitment by HLA class I (HLA I) Ab-activated endothelium. We used a panel of murine mAbs of different subclasses to crosslink HLA I on human aortic, venous, and microvascular endothelial cells and measured the binding of human monocytic cell lines and peripheral blood monocytes. Both anti-HLA I murine (m)IgG1 and mIgG2a induced endothelial P-selectin, which was required for monocyte adhesion to endothelium irrespective of subclass. mIgG2a but not mIgG1 could bind human FcγRs. Accordingly, HLA I mIgG2a but not mIgG1 treatment of endothelial cells significantly augmented recruitment, predominantly through FcγRI, and, to a lesser extent, FcγRIIa. Moreover, HLA I mIgG2a promoted firm adhesion of monocytes to ICAM-1 through Mac-1, which may explain the prominence of monocytes during AMR. We confirmed these observations using human HLA allele-specific mAbs and IgG purified from transplant patient sera. HLA I Abs universally elicit endothelial exocytosis leading to monocyte adherence, implying that P-selectin is a putative therapeutic target to prevent macrophage infiltration during AMR. Importantly, the subclass of donor-specific Ab may influence its pathogenesis. These results imply that human IgG1 and human IgG3 should have a greater capacity to trigger monocyte infiltration into the graft than IgG2 or IgG4 due to enhancement by FcγR interactions.

Korean indigenous bacterial species with valid names belonging to the phylum Actinobacteria.

PubMed

Bae, Kyung Sook; Kim, Mi Sun; Lee, Ji Hee; Kang, Joo Won; Kim, Dae In; Lee, Ji Hee; Seong, Chi Nam

2016-12-01

To understand the isolation and classification state of actinobacterial species with valid names for Korean indigenous isolates, isolation source, regional origin, and taxonomic affiliation of the isolates were studied. At the time of this writing, the phylum Actinobacteria consisted of only one class, Actinobacteria, including five subclasses, 10 orders, 56 families, and 330 genera. Moreover, new taxa of this phylum continue to be discovered. Korean actinobacterial species with a valid name has been reported from 1995 as Tsukamurella inchonensis isolated from a clinical specimen. In 1997, Streptomyces seoulensis was validated with the isolate from the natural Korean environment. Until Feb. 2016, 256 actinobacterial species with valid names originated from Korean territory were listed on LPSN. The species were affiliated with three subclasses (Acidimicrobidae, Actinobacteridae, and Rubrobacteridae), four orders (Acidimicrobiales, Actinomycetales, Bifidobacteriales, and Solirubrobacterales), 12 suborders, 36 families, and 93 genera. Most of the species belonged to the subclass Actinobacteridae, and almost of the members of this subclass were affiliated with the order Actinomycetales. A number of novel isolates belonged to the families Nocardioidaceae, Microbacteriaceae, Intrasporangiaceae, and Streptomycetaceae as well as the genera Nocardioides, Streptomyces, and Microbacterium. Twenty-six novel genera and one novel family, Motilibacteraceae, were created first with Korean indigenous isolates. Most of the Korean indigenous actionobacterial species were isolated from natural environments such as soil, seawater, tidal flat sediment, and fresh-water. A considerable number of species were isolated from artificial resources such as fermented foods, wastewater, compost, biofilm, and water-cooling systems or clinical specimens. Korean indigenous actinobacterial species were isolated from whole territory of Korea, and especially a large number of species were from Jeju, Gyeonggi, Jeonnam, Daejeon, and Chungnam. A large number of novel actinobacterial species continue to be discovered since the Korean government is encouraging the search for new bacterial species and researchers are endeavoring to find out novel strains from extreme or untapped environments.

Genetic profile based upon 15 microsatellites of four caste groups of the eastern Indian state, Bihar.

PubMed

Ashma, R; Kashyap, V K

2003-01-01

The formation of caste groups among the Hindu community and the practice of endogamy exert a great impact on the genetic structure and diversity of the Indian population. Allele frequency data of 15 microsatellite loci clearly portray the genetic diversity and relatedness among four socio-culturally advanced caste groups: Brahmin, Bhumihar, Rajput and Kayasth of Caucasoid ethnicity of Bihar. The study seeks to understand the impact of the man-made caste system on the genetic profile of the four major caste groups of Bihar. Computation of average heterozygosity, most frequent allele, allele diversity and coefficient of gene differentiation (Gst), along with genetic distance (DA)and principal coordinate analysis were performed to assess intra-population and inter-population diversity. The average Gst value for all the loci was 0.012 +/- 0.0033, and the level of average heterozygosity was approximately 75.5%, indicating genetic similarity and intra-population diversity. Genetic distance (DA) values and the phylogenetic tree along with other higher caste groups of India indicate the relative distance between them. The present study clearly depicts the genetic profile of these caste groups, their inherent closeness in the past, and the impact of the imposed caste system that later restricted the gene flow. The study highlights the status of Bhumihar and Kayasth in the Hindu caste system. The former was found clustering with the Brahmin group (as expected, since Bhumihar is known to be a subclass of Brahmin), whereas the distance between the Brahmin and Kayasth caste groups was found to be large. North-eastern Indian Mongoloids form a separate cluster.

Improvement of the omega 3 index of healthy subjects does not alter the effects of dietary saturated fats or n-6PUFA on LDL profiles.

PubMed

Dias, Cintia B; Amigó, Núria; Wood, Lisa G; Mallol, Roger; Correig, Xavier; Garg, Manohar L

2017-03-01

Dietary fat composition is known to modulate circulating lipid and lipoprotein levels. Although supplementation with long chain omega-3 polyunsaturated fatty acids (LCn-3PUFA) has been shown to reduce plasma triglyceride levels, the effect of the interactions between LCn-3PUFA and the major dietary fats consumed has not been previously investigated. In a randomized controlled parallel design clinical intervention, we examined the effect of diets rich in either saturated fatty acids (SFA) or omega-6 polyunsaturated fatty acids (n-6PUFA) on plasma lipid levels and lipoprotein profiles (lipoprotein size, concentration and distribution in subclasses) in subjects with an adequate omega 3 index. Twenty six healthy subjects went through a four-week pre-supplementation period with LCn-3PUFA and were then randomized to diets rich in either n-6PUFA or SFA both supplemented with LCn-3PUFA. The diet rich in n-6PUFA decreased low density lipoprotein (LDL) particle concentration (-8%, p=0.013) and LDL cholesterol (LDL-C) level (-8%, p=0.021), while the saturated fat rich diet did not affect LDL particle concentration or LDL-C levels significantly. Nevertheless, dietary saturated fatty acids increased LCn-3PUFA in plasma and tissue lipids compared with n-6PUFA, potentially reducing other cardiovascular risk factors such as inflammation and clotting tendency. Improvement on the omega 3 index of healthy subjects did not alter the known effects of dietary saturated fats and n-6PUFA on LDL profiles. Copyright © 2016 Elsevier Inc. All rights reserved.

Gene integrated set profile analysis: a context-based approach for inferring biological endpoints

PubMed Central

Kowalski, Jeanne; Dwivedi, Bhakti; Newman, Scott; Switchenko, Jeffery M.; Pauly, Rini; Gutman, David A.; Arora, Jyoti; Gandhi, Khanjan; Ainslie, Kylie; Doho, Gregory; Qin, Zhaohui; Moreno, Carlos S.; Rossi, Michael R.; Vertino, Paula M.; Lonial, Sagar; Bernal-Mizrachi, Leon; Boise, Lawrence H.

2016-01-01

The identification of genes with specific patterns of change (e.g. down-regulated and methylated) as phenotype drivers or samples with similar profiles for a given gene set as drivers of clinical outcome, requires the integration of several genomic data types for which an ‘integrate by intersection’ (IBI) approach is often applied. In this approach, results from separate analyses of each data type are intersected, which has the limitation of a smaller intersection with more data types. We introduce a new method, GISPA (Gene Integrated Set Profile Analysis) for integrated genomic analysis and its variation, SISPA (Sample Integrated Set Profile Analysis) for defining respective genes and samples with the context of similar, a priori specified molecular profiles. With GISPA, the user defines a molecular profile that is compared among several classes and obtains ranked gene sets that satisfy the profile as drivers of each class. With SISPA, the user defines a gene set that satisfies a profile and obtains sample groups of profile activity. Our results from applying GISPA to human multiple myeloma (MM) cell lines contained genes of known profiles and importance, along with several novel targets, and their further SISPA application to MM coMMpass trial data showed clinical relevance. PMID:26826710

Experimental verification, and domain definition, of structural alerts for protein binding: epoxides, lactones, nitroso, nitros, aldehydes and ketones.

PubMed

Nelms, M D; Cronin, M T D; Schultz, T W; Enoch, S J

2013-01-01

This study outlines how a combination of in chemico and Tetrahymena pyriformis data can be used to define the applicability domain of selected structural alerts within the profilers of the OECD QSAR Toolbox. Thirty-three chemicals were profiled using the OECD and OASIS profilers, enabling the applicability domain of six structural alerts to be defined, the alerts being: epoxides, lactones, nitrosos, nitros, aldehydes and ketones. Analysis of the experimental data showed the applicability domains for the epoxide, nitroso, aldehyde and ketone structural alerts to be well defined. In contrast, the data showed the applicability domains for the lactone and nitro structural alerts needed modifying. The accurate definition of the applicability domain for structural alerts within in silico profilers is important due to their use in the chemical category in predictive and regulatory toxicology. This study highlights the importance of utilizing multiple profilers in category formation.

Caring for the Patient With Limited Systemic Scleroderma.

PubMed

Lachner, Kelly Denise

2016-01-01

Systemic scleroderma (systemic sclerosis) is a rare, autoimmune, collagen-vascular disease of unknown etiology that affects the connective tissues of the skin, internal organs, as well as the small blood vessels. There are 3 subclasses of systemic scleroderma: limited cutaneous, diffuse cutaneous, and sine scleroderma. Prognosis depends on the extent of organ involvement. Complications of systemic scleroderma can involve the cardiovascular, pulmonary, gastrointestinal, renal, integumentary, and the skeletal-muscular systems. Because systemic scleroderma is not common, many orthopaedic nurses may be unfamiliar with how to best provide care. This article provides information about the complexity of the different types of this disease and the basic nursing care of the patient with the most common subclass of systemic scleroderma, limited cutaneous systemic scleroderma.

Shaping electrocatalysis through tailored nanomaterials

DOE PAGES

Kang, Yijin; Yang, Peidong; Markovic, Nenad M.; ...

2016-09-21

Electrocatalysis is a subclass of heterogeneous catalysis that is aimed towards increase of the electrochemical reaction rates that are taking place at the surface of electrodes. Real-world electrocatalysts are usually based on precious metals in the form of nanoparticles due to their high surface-to-volume ratio, which enables better utilization of employed materials. Ability to tailor nanostructure of an electrocatalyst is critical in order to tune their electrocatalytic properties. Over the last decade, that has mainly been achieved through implementation of fundamental studies performed on well-defined extended surfaces with distinct single crystalline and polycrystalline structures. Based on these studies, it hasmore » been demonstrated that performance of an electrocatalyst could be significantly changed through the control of size, composition, morphology and architecture of employed nanomaterials. Here, this review outlines the following steps in the process of rational development of an efficient electrocatalyst: 1) electrochemical properties of well-defined surfaces, 2) synthesis and characterization of different classes of electrocatalysts, and 3) correlation between physical properties (size, shape, composition and morphology) and electrochemical behavior (adsorption, electrocatalytic activity and durability) of electrocatalyst. In addition, this is a brief summary of the novel research platforms in the development of functional nano materials for energy conversion and storage applications such as fuel cells electrolyzers and batteries.« less

The assessment of UV resources over Northern Eurasia

NASA Astrophysics Data System (ADS)

Chubarova, Natalia; Zhdanova, Yekaterina

2013-05-01

The spatial and temporal distribution of UV resources was assessed over Northern Eurasia by using RT modeling (8 stream DISORT RT code) with 1×1 degree grid and month resolution. For this purpose a special dataset of main input geophysical parameters (total ozone content, aerosol characteristics, surface UV albedo, and UV cloud modification factor) has been developed. To define the UV resources both erythemally-weighted and vitamin D irradiances were used. In order to better quantify vitamin D irradiance threshold we accounted for a body exposure fraction S as a function of surface effective temperature. The UV resources are defined by using several classes and subclasses: UV deficiency, UV optimum, and UV excess. They were evaluated for clear and typical cloudy conditions for different skin types. We show that for typical cloudy conditions in winter (January) there are only few regions in Europe at the south of Spain (southward 43°N) with conditions of UV optimum for people with skin type 2 and no such conditions for people with skin type 4. In summer (July) UV optimum for skin 2 is observed northward 63°N with a boundary biased towards higher latitudes at the east, while for skin type 4 these conditions are observed over the most territory of Northern Eurasia.

Soybean TCP transcription factors: Evolution, classification, protein interaction and stress and hormone responsiveness.

PubMed

Feng, Zhi-Juan; Xu, Sheng-Chun; Liu, Na; Zhang, Gu-Wen; Hu, Qi-Zan; Gong, Ya-Ming

2018-06-01

TEOSINTE-BRANCHED1/CYCLOIDEA/PCF (TCP) transcription factors, a family of plant-specific proteins, play crucial roles in plant growth and development and stress response. However, systematical information is unknown regarding the TCP gene family in soybean. In the present study, a total of 54 GmTCPs were identified in soybean, which were grouped into 11 groups with the typical TCP conserved domains. Phylogenetic relationship, protein motif and gene structure analyses distinguished the GmTCPs into two homology classes: Class I and Class II. Class II was then differentiated into two subclasses: CIN and CYC/TB1. Unique cis-element number and composition existed in the promoter regions which might be involved in the gene transcriptional regulation of different GmTCPs. Tissue expression analysis demonstrated the diverse spatiotemporal expression profiles of GmTCPs. Furthermore, the interaction protein of one previously functionally unknown TCP protein-GmTCP8 was investigated. Yeast two-hybrid assay showed the interaction between GmTCP8 and an abscisic acid receptor (GmPYL10). QRT-PCR assays indicated the distinct expression profiles of GmTCPs in response to abiotic stresses (heat, drought and salt) and stress-related signals (abscisic acid, brassinolide, salicylicacid and methyl jasmonate). These results will facilitate to uncover the possible roles of GmTCPs under abiotic stress and hormone signal responses in soybean. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

A Significantly off-center 56Ni Distribution for the Low-Luminosity Type Ia Supernova SN 2016brx from the 100IAS survey

NASA Astrophysics Data System (ADS)

Dong, Subo; Katz, Boaz; Kollmeier, Juna A.; Kushnir, Doron; Elias-Rosa, N.; Bose, Subhash; Morrell, Nidia; Prieto, J. L.; Chen, Ping; Kochanek, C. S.; Brandt, G. M.; Holoien, T. W.-S.; Gal-Yam, Avishay; Morales-Garoffolo, Antonia; Parker, Stuart; Phillips, M. M.; Piro, Anthony L.; Shappee, B. J.; Simon, Joshua D.; Stanek, K. Z.

2018-06-01

We present nebular-phase spectra of the Type Ia supernova (SN Ia) 2016brx, a member of the 1991bg-like subclass that lies at the faint end of the SN Ia luminosity function. Nebular spectra are available for only three other 1991bg-like SNe, and their Co line centers are all within ≲ 500 km/s of each other. In contrast, the nebular Co line center of SN 2016brx is blue-shifted by >1500 km/s compared to them and by ≈1200 km/s compared to the rest frame. This is a significant shift relative to the narrow nebular line velocity dispersion of ≲ 2000 km/s of these SNe. The large range of nebular line shifts implies that the 56Ni in the ejecta of SN 1991bg-like events is off-center by ˜1000 km/s rather than universally centrally confined as previously suggested. With the addition of SN 2016brx, the Co nebular line shapes of 1991bg-like objects appear to connect with the brighter SNe Ia that show double-peaked profiles, hinting at a continuous distribution of line profiles among SNe Ia. One class of models to produce both off-center and bi-modal 56Ni distributions is collisions of white dwarfs with unequal and equal masses.

47 CFR 32.2321 - Customer premises wiring.

Code of Federal Regulations, 2012 CFR

2012-10-01

... SYSTEM OF ACCOUNTS FOR TELECOMMUNICATIONS COMPANIES Instructions for Balance Sheet Accounts § 32.2321... 232, Station Connections, inside wiring subclass. (b) Embedded Customer Premises Wiring is that...

47 CFR 32.2321 - Customer premises wiring.

Code of Federal Regulations, 2011 CFR

2011-10-01

... SYSTEM OF ACCOUNTS FOR TELECOMMUNICATIONS COMPANIES Instructions for Balance Sheet Accounts § 32.2321... 232, Station Connections, inside wiring subclass. (b) Embedded Customer Premises Wiring is that...

Data reduction and calibration for LAMOST survey

NASA Astrophysics Data System (ADS)

Luo, Ali; Zhang, Jiannan; Chen, Jianjun; Song, Yihan; Wu, Yue; Bai, Zhongrui; Wang, Fengfei; Du, Bing; Zhang, Haotong

2014-01-01

There are three data pipelines for LAMOST survey. The raw data is reduced to one dimension spectra by the data reduction pipeline(2D pipeline), the extracted spectra are classified and measured by the spectral analysis pipeline(1D pipeline), while stellar parameters are measured by LASP pipeline. (a) The data reduction pipeline. The main tasks of the data reduction pipeline include bias calibration, flat field, spectra extraction, sky subtraction, wavelength calibration, exposure merging and wavelength band connection. (b) The spectra analysis pipeline. This pipeline is designed to classify and identify objects from the extracted spectra and to measure their redshift (or radial velocity). The PCAZ (Glazebrook et al. 1998) method is applied to do the classification and redshift measurement. (c) Stellar parameters LASP. Stellar parameters pipeline (LASP) is to estimate stellar atmospheric parameters, e.g. effective temperature Teff, surface gravity log g, and metallicity [Fe/H], for F, G and K type stars. To effectively determine those fundamental stellar measurements, three steps with different methods are employed. The first step utilizes the line indices to approximately define the effective temperature range of the analyzed star. Secondly, a set of the initial approximate values of the three parameters are given based on template fitting method. Finally, we exploit ULySS (Koleva et al. 2009) to give the final values of parameters through minimizing the χ 2 value between the observed spectrum and a multidimensional grid of model spectra which is generated by an interpolating of ELODIE library. There are two other classification for A type star and M type star. For A type star, standard MK system is employed (Gray et al. 2009) to give each object temperature class and luminosity type. For M type star, they are classified into subclasses by an improved Hammer method, and metallicity of each objects is also given. During the pilot survey, algorithms were improved and the pipelines were tested. The products of LAMOST survey will include extracted and calibrated spectra in FITS format, a catalog of FGK stars with stellar parameters, a catalog of M dwarf with subclass and metallicity, and a catalog of A type star with MK classification. A part of the pilot survey data, including about 319 000 high quality spectra with SNR > 10, a catalog of stellar parameters of FGK stars and another catalog of a subclass of M type stars have been released to the public in August 2012 (Luo et al. 2012). The general survey started from October 2012, and completed the first year survey. The formal data release one (DR1) is being prepared, which will include both pilot survey and first year general survey, and planed to be released under the LAMOST data policy.

[The impact of a 14- day regular physical exercise regime on the concentration of the classes and subclasses of lipoprotein particles in young subjects with a sedentary lifestyle].

PubMed

Sabaka, P; Dukát, A; Oravec, S; Mistríková, L; Baláž, D; Bendžala, M; Gašpar, L

2013-10-01

Recommendations from the cardiological professional companies working in the area of primary prevention of cardiovascular diseases put an emphasis on regular aerobic physical activity. Its positive effect on both cardiovascular and overall mortality has repea-tedly been proven by the observations of prospective and cross sectional epidemiological studies. One of the possible explanations of this positive effect is a change in the concentration of lipoprotein classes and their subclasses, which is expressed as a change in their average size. In a group of young healthy men and women with a sedentary lifestyle we observed the effect of medium intensive physical exercise in the form of a 30- minute slow run per day lasting for 14 days. The concentration of lipoprotein classes and subclasses were determined through the method of a linear electrophoresis in polyacrylamide gel. In the observed group we found a statistically significant decrease of VLDL, large IDL particles, medium sized LDL, small dense LDL, and medium sized HDL particles. In the light of current knowledge all these lipoprotein particles are deemed as atherogenic. Thus, as little as 14 days of regular exercising has a positive effect on the concentration of plasmatic lipoproteins, and emphasises the role of regular physical activity in the primary prevention of cardiovascular diseases.

An unbalanced spectra classification method based on entropy

NASA Astrophysics Data System (ADS)

Liu, Zhong-bao; Zhao, Wen-juan

2017-05-01

How to solve the problem of distinguishing the minority spectra from the majority of the spectra is quite important in astronomy. In view of this, an unbalanced spectra classification method based on entropy (USCM) is proposed in this paper to deal with the unbalanced spectra classification problem. USCM greatly improves the performances of the traditional classifiers on distinguishing the minority spectra as it takes the data distribution into consideration in the process of classification. However, its time complexity is exponential with the training size, and therefore, it can only deal with the problem of small- and medium-scale classification. How to solve the large-scale classification problem is quite important to USCM. It can be easily obtained by mathematical computation that the dual form of USCM is equivalent to the minimum enclosing ball (MEB), and core vector machine (CVM) is introduced, USCM based on CVM is proposed to deal with the large-scale classification problem. Several comparative experiments on the 4 subclasses of K-type spectra, 3 subclasses of F-type spectra and 3 subclasses of G-type spectra from Sloan Digital Sky Survey (SDSS) verify USCM and USCM based on CVM perform better than kNN (k nearest neighbor) and SVM (support vector machine) in dealing with the problem of rare spectra mining respectively on the small- and medium-scale datasets and the large-scale datasets.

Flavonoids, Flavonoid Subclasses, and Esophageal Cancer Risk: A Meta-Analysis of Epidemiologic Studies

PubMed Central

Cui, Lingling; Liu, Xinxin; Tian, Yalan; Xie, Chen; Li, Qianwen; Cui, Han; Sun, Changqing

2016-01-01

Flavonoids have been suggested to play a chemopreventive role in carcinogenesis. However, the epidemiologic studies assessing dietary intake of flavonoids and esophageal cancer risk have yielded inconsistent results. This study was designed to examine the association between flavonoids, each flavonoid subclass, and the risk of esophageal cancer with a meta-analysis approach. We searched for all relevant studies with a prospective cohort or case-control study design published from January 1990 to April 2016, using PUBMED, EMBASE, and Web of Science. Pooled odds ratios (ORs) were calculated using fixed or random-effect models. In total, seven articles including 2629 cases and 481,193 non-cases were selected for the meta-analysis. Comparing the highest-intake patients with the lowest-intake patients for total flavonoids and for each flavonoid subclass, we found that anthocyanidins (OR = 0.60, 95% CI: 0.49–0.74), flavanones (OR = 0.65, 95% CI: 0.49–0.86), and flavones (OR = 0.78, 95% CI 0.64–0.95) were inversely associated with the risk of esophageal cancer. However, total flavonoids showed marginal association with esophageal cancer risk (OR = 0.78, 95% CI: 0.59–1.04). In conclusion, our study suggested that dietary intake of total flavonoids, anthocyanidins, flavanones, and flavones might reduce the risk of esophageal cancer. PMID:27338463

Recombinant C-terminal 311 amino acids of HapS adhesin as a vaccine candidate for nontypeable Haemophilus influenzae: A study on immunoreactivity in Balb/C mouse.

PubMed

Tabatabaee Bafroee, Akram Sadat; Siadat, Seyed Davar; Mousavi, Seyed Fazlollah; Aghasadeghi, Mohammad Reza; Khorsand, Hashem; Nejati, Mehdi; Sadat, Seyed Mehdi; Mahdavi, Mehdi

2016-09-01

Hap, an auto-transporter protein, is an antigenically conserved adhesion protein which is present on both typeable and nontypeable Haemophilus influenzae. This protein has central role in bacterial attachment to respiratory tract epithelial cells. A 1000bp C-terminal fragment of Hap passenger domain (HapS) from nontypeable Haemophilus influenzae was cloned into a prokaryotic expression vector, pET-24a. BALB/c mice were immunized subcutaneously with purified rC-HapS. Serum IgG responses to purified rC-HapS, serum IgG subclasses were determined by ELISA and functional activity of antibodies was examined by Serum Bactericidal Assay. The output of rC-HapS was approximately 62% of the total bacterial proteins. Serum IgG responses were significantly increased in immunized group with rC-HapS mixed with Freund's adjuvant in comparison with control groups. Analysis of the serum IgG subclasses showed that the IgG1 subclass was predominant after subcutaneous immunization in BALB/c mice (IgG2a/IgG1 < 1). The sera from rC-HapS immunized animals were strongly bactericidal against nontypeable Haemophilus influenzae. These results suggest that rC-HapS may be a potential vaccine candidate for nontypeable Haemophilus influenzae. Copyright © 2016 Elsevier Ltd. All rights reserved.

From speech to thought: the neuronal basis of cognitive units in non-experimental, real-life communication investigated using ECoG

PubMed Central

Derix, Johanna; Iljina, Olga; Weiske, Johanna; Schulze-Bonhage, Andreas; Aertsen, Ad; Ball, Tonio

2014-01-01

Exchange of thoughts by means of expressive speech is fundamental to human communication. However, the neuronal basis of real-life communication in general, and of verbal exchange of ideas in particular, has rarely been studied until now. Here, our aim was to establish an approach for exploring the neuronal processes related to cognitive “idea” units (IUs) in conditions of non-experimental speech production. We investigated whether such units corresponding to single, coherent chunks of speech with syntactically-defined borders, are useful to unravel the neuronal mechanisms underlying real-world human cognition. To this aim, we employed simultaneous electrocorticography (ECoG) and video recordings obtained in pre-neurosurgical diagnostics of epilepsy patients. We transcribed non-experimental, daily hospital conversations, identified IUs in transcriptions of the patients' speech, classified the obtained IUs according to a previously-proposed taxonomy focusing on memory content, and investigated the underlying neuronal activity. In each of our three subjects, we were able to collect a large number of IUs which could be assigned to different functional IU subclasses with a high inter-rater agreement. Robust IU-onset-related changes in spectral magnitude could be observed in high gamma frequencies (70–150 Hz) on the inferior lateral convexity and in the superior temporal cortex regardless of the IU content. A comparison of the topography of these responses with mouth motor and speech areas identified by electrocortical stimulation showed that IUs might be of use for extraoperative mapping of eloquent cortex (average sensitivity: 44.4%, average specificity: 91.1%). High gamma responses specific to memory-related IU subclasses were observed in the inferior parietal and prefrontal regions. IU-based analysis of ECoG recordings during non-experimental communication thus elicits topographically- and functionally-specific effects. We conclude that segmentation of spontaneous real-world speech in linguistically-motivated units is a promising strategy for elucidating the neuronal basis of mental processing during non-experimental communication. PMID:24982625

Effect of liposomal formulations and immunostimulating peptidoglycan monomer (PGM) on the immune reaction to ovalbumin in mice.

PubMed

Habjanec, Lidija; Frkanec, Ruza; Halassy, Beata; Tomasić, Jelka

2006-01-01

The adjuvant activity of liposomes and immunostimulating peptidoglycan monomer (PGM) in different formulations has been studied in mice model using ovalbumin (OVA) as an antigen. PGM is a natural compound of bacterial origin with well-defined chemical structure: GlcNAc-MurNAc-L-Ala-D-isoGln-mesoDpm(epsilonNH2)-D-Ala-D-Ala. It is a non-toxic, non-pyrogenic, and water-soluble immunostimulator. The aim of this study was to investigate the influence of different liposomal formulations of OVA, with or without PGM, on the production of total IgG, as well as of IgG1 and IgG2a subclasses of OVA-specific antibodies (as indicators of Th2 and Th1 type of immune response, respectively). CBA mice were immunized s.c. with OVA mixed with liposomes, OVA with PGM mixed with liposomes, OVA encapsulated into liposomes and OVA with PGM encapsulated into liposomes. Control groups were OVA in saline, OVA with PGM in saline, and OVA in CFA/IFA adjuvant formulation. The entrapment efficacy of OVA was monitored by HPLC method. The adjuvant activity of the mixture of OVA and empty liposomes, the mixture of OVA, PGM, and liposomes and PGM encapsulated with OVA into liposomes on production of total anti-OVA IgG was demonstrated. The mixture of PGM and liposomes exhibited additive immunostimulating effect on the production of antigen-specific IgGs. The analysis of IgG subclasses revealed that encapsulation of OVA into liposomes favors the stimulation of IgG2a antibodies, indicating the switch toward the Th1 type of immune response. When encapsulated into liposomes or mixed with liposomes, PGM induced a switch from Th1 to Th2 type of immune response. It could be concluded that appropriate formulations of antigen, PGM, and liposomes differently affect the humoral immune response and direct the switch in the type of immune response (Th1/Th2).

IgA Fc receptors.

PubMed

Monteiro, Renato C; Van De Winkel, Jan G J

2003-01-01

The IgA receptor family comprises a number of surface receptors including the polymeric Ig receptor involved in epithelial transport of IgA/IgM, the myeloid specific IgA Fc receptor (FcalphaRI or CD89), the Fcalpha/muR, and at least two alternative IgA receptors. These are the asialoglycoprotein receptor and the transferrin receptor, which have been implicated in IgA catabolism, and tissue IgA deposition. In this review we focus on the biology of FcalphaRI (CD89). FcalphaRI is expressed on neutrophils, eosinophils, monocytes/macrophages, dendritic cells, and Kupffer cells. This receptor represents a heterogeneously glycosylated transmembrane protein that binds both IgA subclasses with low affinity. A single gene encoding FcalphaRI has been isolated, which is located within the leukocyte receptor cluster on chromosome 19. The FcalphaRI alpha chain lacks canonical signal transduction domains but can associate with the FcR gamma-chain that bears an activation motif (ITAM) in the cytoplasmic domain, allowing activatory functions. FcalphaRI expressed alone mediates endocytosis and recyling of IgA. No FcalphaRI homologue has been defined in the mouse, and progress in defining the in vivo role of FcalphaRI has been made using human FcalphaRI transgenic (Tg) mice. FcalphaRI-Tg mice demonstrated FcalphaRI expression on Kupffer cells and so defined a key role for the receptor in mucosal defense. The receptor functions as a second line of antibacterial defense involving serum IgA rather than secretory IgA. Studies in FcalphaRI-Tg mice, furthermore, defined an essential role for soluble FcalphaRI in the development of IgA nephropathy by formation of circulating IgA-FcalphaRI complexes. Finally, recent work points out a role for human IgA in treatment of infectious and neoplastic diseases.

The IgG2a antibody response to thyroglobulin is linked to the Igh locus in mouse.

PubMed

Kuppers, R C; Epstein, L D; Outschoorn, I M; Rose, N R

1994-01-01

The IgG-subclass usage by several strains of mice in the response to immunization with mouse thyroglobulin (mTg) was examined in the experimental autoimmune thyroiditis model. While the subclass usage by most mouse strains was similar, the Ighb allotype-bearing mice consistently produced lower IgG2a levels to mTg. Using CBA-Ighb congenic and recombinant inbred strains of mice, the lower level of IgG2a in the Ighb mouse was mapped to the Igh locus. The regulation of IgG2a appeared to be cis controlled, as the CBA x C57BL/6F1 mouse also produced reduced IgG2a of the Ighb (B6) allotype but not of the Ighj (CBA) allotype.

Understanding the tumor immune microenvironment (TIME) for effective therapy

PubMed Central

Binnewies, Mikhail; Roberts, Edward W.; Kersten, Kelly; Chan, Vincent; Fearon, Douglas F.; Merad, Miriam; Coussens, Lisa M.; Gabrilovich, Dmitry I.; Ostrand-Rosenberg, Suzanne; Hedrick, Catherine C.; Vonderheide, Robert H.; Pittet, Mikael J.; Jain, Rakesh K.; Zou, Weiping; Howcroft, T. Kevin; Woodhouse, Elisa C.; Weinberg, Robert A.; Krummel, Matthew F.

2018-01-01

The clinical successes in immunotherapy have been both astounding and at the same time unsatisfactory. Countless patients with varied tumor types have seen pronounced clinical response with immunotherapeutic intervention; however, many more patients have experienced minimal or no clinical benefit when provided the same treatment. As technology has advanced, so has the understanding of the complexity and diversity of the immune context of the tumor microenvironment and its influence on response to therapy. It has been possible to identify different subclasses of immune environment that have an influence on tumor initiation and response and therapy; by parsing the unique classes and subclasses of tumor immune microenvironment (TIME) that exist within a patient’s tumor, the ability to predict and guide immunotherapeutic responsiveness will improve, and new therapeutic targets will be revealed. PMID:29686425

Flaring activity of the SFXT IGR J16418-4532

NASA Astrophysics Data System (ADS)

Poliakov, D.; Aitov, V.; Ikhsanov, N.

2017-12-01

Supergiant fast X-ray transients (SFXTs) are a sub-class of wind-fed High Mass X-ray Binaries (HMXB) in which the normal companion is a supergiant. These systems were collected in a sub-class because of short flares (a few hours duration) in which the X-ray luminosity increases by a few orders of magnitude. One of the members of SFXTs is the X-ray 1212 s pulsar IGR J16418-4532, which is characterized by a high quiescent X-ray luminosity and flaring on a short timescale. We show that the degenerate component of the system is either a magnetar which accretes matter from a Keplerian disk of quasi-spherical flow, or a regularly magnetized neutron star which rotates near spin equilibrium and accretes matter from a non-Keplerian magnetic disk.

Manipulating Environmental Time Series in Python/Numpy: the Scikits.Timeseries Package and its Applications.

NASA Astrophysics Data System (ADS)

Gerard-Marchant, P. G.

2008-12-01

Numpy is a free, open source C/Python interface designed for the fast and convenient manipulation of multidimensional numerical arrays. The base object, ndarray, can also be easily be extended to define new objects meeting specific needs. Thanks to its simplicity, efficiency and modularity, numpy and its companion library Scipy have become increasingly popular in the scientific community over the last few years, with application ranging from astronomy and engineering to finances and statistics. Its capacity to handle missing values is particularly appealing when analyzing environmental time series, where irregular data sampling might be an issue. After reviewing the main characteristics of numpy objects and the mechanism of subclassing, we will present the scikits.timeseries package, developed to manipulate single- and multi-variable arrays indexed in time. We will illustrate some typical applications of this package by introducing climpy, a set of extensions designed to help analyzing the impacts of climate variability on environmental data such as precipitations or streamflows.

Coordinated temporal and spatial control of motor neuron and serotonergic neuron generation from a common pool of CNS progenitors.

PubMed

Pattyn, Alexandre; Vallstedt, Anna; Dias, José M; Samad, Omar Abdel; Krumlauf, Robb; Rijli, Filippo M; Brunet, Jean-Francois; Ericson, Johan

2003-03-15

Neural progenitor cells often produce distinct types of neurons in a specific order, but the determinants that control the sequential generation of distinct neuronal subclasses in the vertebrate CNS remain poorly defined. We examined the sequential generation of visceral motor neurons and serotonergic neurons from a common pool of neural progenitors located in the ventral hindbrain. We found that the temporal specification of these neurons varies along the anterior-posterior axis of the hindbrain, and that the timing of their generation critically depends on the integrated activities of Nkx- and Hox-class homeodomain proteins. A primary function of these proteins is to coordinate the spatial and temporal activation of the homeodomain protein Phox2b, which in turn acts as a binary switch in the selection of motor neuron or serotonergic neuronal fate. These findings assign new roles for Nkx, Hox, and Phox2 proteins in the control of temporal neuronal fate determination, and link spatial and temporal patterning of CNS neuronal fates.

Making the Impossible Possible: Strategies for Fast POMDP Monitoring

NASA Technical Reports Server (NTRS)

Washington, Richard; Lau, Sonie (Technical Monitor)

1998-01-01

Systems modeled as partially observable Markov decision processes (POMDPs) can be tracked quickly with three restrictions: all actions are grouped together, the out-degree of each system state is bounded by a constant, and the number of non-zero elements in the belief state is bounded by a (different) constant. With these restrictions, the tracking algorithm operates in constant time and linear space. The first restriction assumes that the action itself is unobservable. The second restriction defines a subclass of POMDPs that covers however a wide range of problems. The third restriction is an approximation technique that can lead to a potentially vexing problem: an observation may be received that has probability according to the restricted belief state. This problem of impossibility will cause the belief state to collapse. In this paper we discuss the tradeoffs between the constant bound on the belief state and the quality of the solution. We concentrate on strategies for overcoming the impossibility problem and demonstrate initial experimental results that indicate promising directions.

Encoding of Fundamental Chemical Entities of Organic Reactivity Interest using chemical ontology and XML.

PubMed

Durairaj, Vijayasarathi; Punnaivanam, Sankar

2015-09-01

Fundamental chemical entities are identified in the context of organic reactivity and classified as appropriate concept classes namely ElectronEntity, AtomEntity, AtomGroupEntity, FunctionalGroupEntity and MolecularEntity. The entity classes and their subclasses are organized into a chemical ontology named "ChemEnt" for the purpose of assertion, restriction and modification of properties through entity relations. Individual instances of entity classes are defined and encoded as a library of chemical entities in XML. The instances of entity classes are distinguished with a unique notation and identification values in order to map them with the ontology definitions. A model GUI named Entity Table is created to view graphical representations of all the entity instances. The detection of chemical entities in chemical structures is achieved through suitable algorithms. The possibility of asserting properties to the entities at different levels and the mechanism of property flow within the hierarchical entity levels is outlined. Copyright © 2015 Elsevier Inc. All rights reserved.

Comparison of visible and near-infrared reflectance spectra of CM2 carbonaceous chondrites and primitive asteroids

NASA Technical Reports Server (NTRS)

Vilas, F.; Hiroi, T.; Zolensky, M. E.

1993-01-01

Spectra of primitive asteroids (defined as C, P, and D classes and associated subclasses) were compared to the limited number of spectra of CM2 carbonaceous chondrites. An absorption feature located at 0.7 microns attributed to an Fe(+2) - Fe(+3) charge transfer absorption in iron oxides in phyllosilicates is apparent in some of the CM2 carbonaceous chondrite spectra and many of the asteroid spectra. Sawyer found a correlation between the area of the 0.7 micron feature and the mean semimajor axis of the asteroids. Spectra of a larger sample of carbonaceous chondrites, including 7 CM2 chondrites, covering a spectral interval of 0.30-2.5 microns were recently obtained using the Relab instrument at Brown University. These spectra were compared with spectrophotometric asteroid observations in a separate abstract. Those spectra of CM2 chondrites were isolated into the UV, visible and near-infrared spectral regions in order to compare them with high-quality narrowband reflectance spectra.

The spectral theorem for quaternionic unbounded normal operators based on the S-spectrum

DOE Office of Scientific and Technical Information (OSTI.GOV)

Alpay, Daniel, E-mail: dany@math.bgu.ac.il; Kimsey, David P., E-mail: dpkimsey@gmail.com; Colombo, Fabrizio, E-mail: fabrizio.colombo@polimi.it

In this paper we prove the spectral theorem for quaternionic unbounded normal operators using the notion of S-spectrum. The proof technique consists of first establishing a spectral theorem for quaternionic bounded normal operators and then using a transformation which maps a quaternionic unbounded normal operator to a quaternionic bounded normal operator. With this paper we complete the foundation of spectral analysis of quaternionic operators. The S-spectrum has been introduced to define the quaternionic functional calculus but it turns out to be the correct object also for the spectral theorem for quaternionic normal operators. The lack of a suitable notion ofmore » spectrum was a major obstruction to fully understand the spectral theorem for quaternionic normal operators. A prime motivation for studying the spectral theorem for quaternionic unbounded normal operators is given by the subclass of unbounded anti-self adjoint quaternionic operators which play a crucial role in the quaternionic quantum mechanics.« less

Divergent Hox Coding and Evasion of Retinoid Signaling Specifies Motor Neurons Innervating Digit Muscles

PubMed Central

Mendelsohn, Alana I.; Dasen, Jeremy S.; Jessell, Thomas M.

2017-01-01

Summary The establishment of spinal motor neuron subclass diversity is achieved through developmental programs that are aligned with the organization of muscle targets in the limb. The evolutionary emergence of digits represents a specialized adaptation of limb morphology, yet it remains unclear how the specification of digit-innervating motor neuron subtypes parallels the elaboration of digits. We show that digit-innervating motor neurons can be defined by selective gene markers and distinguished from other LMC neurons by the expression of a variant Hox gene repertoire and by the failure to express a key enzyme involved in retinoic acid synthesis. This divergent developmental program is sufficient to induce the specification of digit-innervating motor neurons, emphasizing the specialized status of digit control in the evolution of skilled motor behaviors. Our findings suggest that the emergence of digits in the limb is matched by distinct mechanisms for specifying motor neurons that innervate digit muscles. PMID:28190640

[The process of defining the competence profile of the healthcare professions manager in the Veneto Region].

PubMed

Costa, Claudio; Roncoroni, Elisabetta; Saiani, Luisa; Stevanin, Simone; Fanton, Elena; Mantoan, Domenico

2018-01-01

Presented here is the approach used by a multidisciplinary working group fo the drafting of the "core" competence profile of the healthcare professions manager in the Veneto Region. Defining a competence profile allows for specifying a standard for measuring the skills acquired by a professional and the gap level from what is expected by the organization, as well as orienting the preparatory education to carry out the related role.

Automatic genetic optimization approach to two-dimensional blade profile design for steam turbines

DOE Office of Scientific and Technical Information (OSTI.GOV)

Trigg, M.A.; Tubby, G.R.; Sheard, A.G.

1999-01-01

In this paper a systematic approach to the optimization of two-dimensional blade profiles is presented. A genetic optimizer has been developed that modifies the blade profile and calculates its profile loss. This process is automatic, producing profile designs significantly faster and with significantly lower loss than has previously been possible. The optimizer developed uses a genetic algorithm to optimize a two-dimensional profile, defined using 17 parameters, for minimum loss with a given flow condition. The optimizer works with a population of two-dimensional profiles with varied parameters. A CFD mesh is generated for each profile, and the result is analyzed usingmore » a two-dimensional blade-to-blade solver, written for steady viscous compressible flow, to determine profile loss. The loss is used as the measure of a profile`s fitness. The optimizer uses this information to select the members of the next population, applying crossovers, mutations, and elitism in the process. Using this method, the optimizer tends toward the best values for the parameters defining the profile with minimum loss.« less

The effects of treatment on lipoprotein subfractions evaluated by polyacrylamide gel electrophoresis in patients with autoimmune hypothyroidism and hyperthyroidism.

PubMed

Minarikova, Zuzana; Gaspar, Ludovit; Kruzliak, Peter; Celecová, Zuzana; Oravec, Stanislav

2014-10-10

Atherogenic dyslipoproteinemia is one of the most important risk factor for atherosclerotic changes development. Hypothyroidism is one of the most common causes of secondary dyslipidemias which results from reduced LDL clearance and therefore raised levels of LDL and apoB. Association between small dense LDL (sdLDL) presentation and thyroid status has been examinated using polyacrylamide gel electrophoresis for lipoprotein subfractions evaluation. 40 patients with diagnosed autoimmune hypothyroidism and 30 patients with autoimmune hyperthyroidism were treated with thyroxine replacement or thyreo-suppressive treatment. In both groups lipid profiles, LDL subractions, apolipoproteins (apoA1, apoB), apoA1/apoB ratio and atherogenic index of plazma (AIP) were examined before treatment and in state of euthyreosis. Thyroxine replacement therapy significantly reduced levels of total cholesterol (TC), LDL, triglycerides (TG) and also decreased levels of sdLDL (8,55±11,671 vs 0,83±1,693mg/dl; p<0,001), apoB and AIP. For estimation of atherogenic lipoprotein profile existence an AIP evaluation seems to be better than apoB measurement because of the more evident relationship with sdLDL (r=0,538; p<0,01). Thyreo-suppressive therapy significantly increased levels of TC, LDL, TG and apoB. The sdLDL was not found in hyperthyroid patients. Atherogenic lipoprotein profile was present in 52.5% of hypothyroid subjects, which is higher prevalence than in normal, age-related population. Substitution treatment leads to an improvement of the lipid levels, TG, apoB, AIP and LDL subclasses. It significantly changed the presentation of sdLDL - we noticed shift to large, less atherogenic LDL particles. Significantly positive correlation between sdLDL and TAG; sdLDL and VLDL alerts to hypertriglyceridemia as a major cardiovascular risk factor.

Short-term changes in lipoprotein subclasses and C-reactive protein levels of hypertriglyceridemic adults on low-carbohydrate and low-fat diets.

PubMed

Stoernell, Colene K; Tangney, Christy C; Rockway, Susie W

2008-07-01

Diets designed to promote weight loss and improve atherogenic lipid profiles traditionally include a reduction in total fat and, in particular, saturated fats. This study was designed to test the efficacy of a low-fat diet vs a carbohydrate (CHO)-restricted (low-CHO) diet in hypertriglyceridemic patients on lipid profile, weight loss, high-sensitivity C-reactive protein (hs-CRP), and satiety. Twenty-eight hypertriglyceridemic subjects (based on fasting triacylglycerol [TG] levels exceeding 1.69 mmol/L) were randomized to either the low-CHO or low-fat diet for 8 weeks. Fasting bloods were acquired at weeks 0 and 8 and analyzed for lipids and hs-CRP. Body weight and other anthropometric measures were also obtained. Three random 24-hour food recalls were used to assess compliance during the trial and 2 recalls before randomization to permit individualized dietary education. A significant time-by-treatment interaction was observed (P = .045), wherein the small low-density lipoprotein cholesterol concentrations were reduced by 46% in the low-CHO-assigned subjects and increased by 36% for those assigned the low-fat plan. The observed decrease in TG (18%) among low-CHO subjects, in contrast to the 4% increase for low-fat group, was not significant, nor were there significant differences in hs-CRP, overall dietary compliance, satiety, or the magnitude of body weight loss between groups (low-CHO group, -3.8% vs low-fat group, -1.6%). Favorable reductions in small low-density lipoprotein concentrations after 8 weeks suggest that a moderately restricted carbohydrate diet (20% CHO as energy) can promote a less atherogenic lipid profile when compared to the low-fat diet.

Effect of Therapeutic Plasma Exchange on Immunoglobulins in Myasthenia Gravis

PubMed Central

Guptill, Jeffrey T.; Juel, Vern C.; Massey, Janice M.; Anderson, Amanda C.; Chopra, Manisha; Yi, John S.; Esfandiari, Ehsanollah; Buchanan, Tim; Smith, Bryan; Atherfold, Paul; Jones, Emma; Howard, James F.

2017-01-01

An integrated understanding of therapeutic plasma exchange (TPE) effects on immunoglobulins, autoantibodies, and natural or acquired (vaccine) protective antibodies in patients with autoimmune myasthenia gravis (MG) is lacking. Prior studies measured TPE effects in healthy volunteers or heterogeneous autoimmune diseases populations. We prospectively profiled plasma IgA, IgM, IgG, IgG subclasses (IgG1-4), acetylcholine receptor autoantibodies (AChR+), and protective antibodies in patients with AChR+ MG receiving TPE for an exacerbation. TPE was performed according to institutional practice and patients were profiled for up to 12 weeks. Ten patients were enrolled (median age=72.9 years; baseline MG-Composite=21; median TPE treatments=6 during their first course) and all improved. The maximum decrease in all immunoglobulins, including AChR autoantibodies, was achieved on the final day of the first TPE course (approximately 60–70% reduction). Three weeks post-TPE mean AChR autoantibody, total IgG, IgG1 and IgG2 titers were below the reference range and had not recovered to within 20% of baseline, whereas other measured immunoglobulins approached baseline values. We did not generally observe an “overshoot” of immunoglobulins above pre-TPE levels or accelerated recovery of pathologic AChR autoantibodies. Protective antibody profiles showed similar patterns as other IgGs and were detectable at levels associated with protection from infection. A slow return to baseline for IgGs (except IgG3) was observed, and we did not observe any obvious effect of concomitant medications on this recovery. Collectively, these findings enhance our understanding of the immunological effects of TPE and further supports the concept of rapid immunoglobulin depletion for the treatment of patients with MG. PMID:27684107

Effect of therapeutic plasma exchange on immunoglobulins in myasthenia gravis.

PubMed

Guptill, Jeffrey T; Juel, Vern C; Massey, Janice M; Anderson, Amanda C; Chopra, Manisha; Yi, John S; Esfandiari, Ehsanollah; Buchanan, Tim; Smith, Bryan; Atherfold, Paul; Jones, Emma; Howard, James F

2016-11-01

An integrated understanding of therapeutic plasma exchange (TPE) effects on immunoglobulins, autoantibodies, and natural or acquired (vaccine) protective antibodies in patients with autoimmune myasthenia gravis (MG) is lacking. Prior studies measured TPE effects in healthy volunteers or heterogeneous autoimmune disease populations. We prospectively profiled plasma IgA, IgM, IgG, IgG subclasses (IgG1-4), acetylcholine receptor autoantibodies (AChR+), and protective antibodies in patients with AChR + MG receiving TPE for an exacerbation. TPE was performed according to institutional practice and patients were profiled for up to 12 weeks. Ten patients were enrolled (median age = 72.9 years; baseline MG-Composite = 21; median TPE treatments = 6 during their first course) and all improved. The maximum decrease in all immunoglobulins, including AChR autoantibodies, was achieved on the final day of the first TPE course (∼60-70% reduction). Three weeks post-TPE, mean AChR autoantibody, total IgG, IgG1, and IgG2 titers were below the reference range and had not recovered within 20% of baseline, whereas other measured immunoglobulins approached baseline values. We did not generally observe an "overshoot" of immunoglobulins above pre-TPE levels or accelerated recovery of pathologic AChR autoantibodies. Protective antibody profiles showed similar patterns as other IgGs and were detectable at levels associated with protection from infection. A slow return to baseline for IgGs (except IgG3) was observed, and we did not observe any obvious effect of concomitant medications on this recovery. Collectively, these findings enhance our understanding of the immunological effects of TPE and further support the concept of rapid immunoglobulin depletion for the treatment of patients with MG.

7 CFR 810.2203 - Basis of determination.

Code of Federal Regulations, 2010 CFR

2010-01-01

... GRAIN United States Standards for Wheat Principles Governing the Application of Standards § 810.2203..., wheat of other classes, contrasting classes, and subclasses is made on the basis of the grain when free...

Importance of IgG subclasses of anti-Rh antibodies for the detection of Fc-receptor-bearing human lymphocytes.

PubMed

Zupańska, B; Maślanka, K; van Loghem, E

1982-11-01

13 anti-Rh sera were compared for their usefulness in the detection of Fc-receptor-bearing lymphocytes (EAhum test). IgG subclasses of anti-Rh antibodies were determined by the antiglobulin test with monospecific sera and by the detection of Gm allotypic markers in the haemagglutination inhibition test. Six sera with IgG1 + IgG3 or IgG1 + IgG2 + IgG3 antibodies and one with pure IgG3 antibodies were found to be useful, whereas six other sera with only IgG1 were unsuitable for the EAhum test. G3m markers were detected only on the anti-Rh antibodies which were capable of forming rosettes with lymphocytes. The data show that human peripheral lymphocytes possess Fc receptors for IgG3 immunoglobulins.

Classifying bilinear differential equations by linear superposition principle

NASA Astrophysics Data System (ADS)

Zhang, Lijun; Khalique, Chaudry Masood; Ma, Wen-Xiu

2016-09-01

In this paper, we investigate the linear superposition principle of exponential traveling waves to construct a sub-class of N-wave solutions of Hirota bilinear equations. A necessary and sufficient condition for Hirota bilinear equations possessing this specific sub-class of N-wave solutions is presented. We apply this result to find N-wave solutions to the (2+1)-dimensional KP equation, a (3+1)-dimensional generalized Kadomtsev-Petviashvili (KP) equation, a (3+1)-dimensional generalized BKP equation and the (2+1)-dimensional BKP equation. The inverse question, i.e., constructing Hirota Bilinear equations possessing N-wave solutions, is considered and a refined 3-step algorithm is proposed. As examples, we construct two very general kinds of Hirota bilinear equations of order 4 possessing N-wave solutions among which one satisfies dispersion relation and another does not satisfy dispersion relation.

Parameterization of the shape of intracranial saccular aneurysms using Legendre polynomials.

PubMed

Banatwala, M; Farley, C; Feinberg, D; Humphrey, J D

2005-04-01

Our recent studies of the nonlinear mechanics of saccular aneurysms suggest that it is unlikely that these lesions enlarge or rupture via material (limit point) or dynamic (resonance) instabilities. Rather, there is a growing body of evidence from both vascular biology and biomechanical analyses that implicate mechanosensitive growth and remodeling processes. There is, therefore, a pressing need to quantify regional multiaxial wall stresses which, because of the membrane-like behavior of many aneurysms, necessitates better information on the applied loads and regional surface curvatures. Herein, we present and illustrate a method whereby regional curvatures can be estimated easily for sub-classes of human aneurysms based on clinically available data from magnetic resonance angiography (MRA). Whereas Legendre polynomials are used to illustrate this approach, different functions may prove useful for different sub-classes of lesions.

Representations for implicit constitutive relations describing non-dissipative response of isotropic materials

NASA Astrophysics Data System (ADS)

Gokulnath, C.; Saravanan, U.; Rajagopal, K. R.

2017-12-01

A methodology for obtaining implicit constitutive representations involving the Cauchy stress and the Hencky strain for isotropic materials undergoing a non-dissipative process is developed. Using this methodology, a general constitutive representation for a subclass of implicit models relating the Cauchy stress and the Hencky strain is obtained for an isotropic material with no internal constraints. It is shown that even for this subclass, unlike classical Green elasticity, one has to specify three potentials to relate the Cauchy stress and the Hencky strain. Then, a procedure to obtain implicit constitutive representations for isotropic materials with internal constraints is presented. As an illustration, it is shown that for incompressible materials the Cauchy stress and the Hencky strain could be related through a single potential. Finally, constitutive approximations are obtained when the displacement gradient is small.

Isoelectric focusing-affinity immunoblot analysis of mouse monoclonal antibodies to the four human IgG subclasses

NASA Technical Reports Server (NTRS)

Hamilton, Robert G.; Roebber, Marianne; Rodkey, L. Scott; Reimer, Charles B.

1987-01-01

Isoelectric focusing (IEF)/affinity immunoblotting and enzyme-linked immunosorbent assay (ELISA) were used for parallel analysis of murine monoclonal antihuman IgG-subclass antisera (MoAbs). Coomassie Blue-stained protein bands in the pH region 5.5-8.0 were shown to be murine IgG by direct blotting onto nitrocellulose followed by detection with conjugated antimouse IgG. Use of IgG myeloma antigen-coated nitrocellulose in the IEF-affinity immunoblot allowed detection of the charge microheterogeneity of MoAbs. The MoAb group contained one to five major dense bands flanked by up to four minor fainter bands, all with pIs ranging from 6.1 to 7.8. Semiquantitative estimates of binding specificity in the IEF-affinity blot compared well with cross-reactivity data obtained from a quantitative ELISA.

[Modern polyurethanes in cardiovascular surgery].

PubMed

Gostev, A A; Laktionov, P P; Karpenko, A A

Currently, there is great clinical demand for synthetic tissue-engineered cardiovascular prostheses with good long-term patency. Polyurethanes belong to the class of polymers with excellent bio- and hemocompatibility. They are known to possess good mechanical properties, but are prone to processes of degradation in conditions of functioning in living organisms. Attempts at solving this problem have resulted in the development of various new subclasses of polyurethanes such as thermoplastic polyether polyurethanes, polyurethanes with a silicone segment, polycarbonate polyurethanes and nanocomposite polyurethanes. This was accompanied and followed by offering a series of new technologies of production of implantable medical devices such as vascular grafts, heart valves and others. In the presented review, we discuss biological and mechanical properties of modern subclasses of polyurethanes, as well as modern methods of manufacturing implantable medical devices made of polyurethanes, especially small-diameter vascular prostheses.

Using effort information with change-in-ratio data for population estimation

USGS Publications Warehouse

Udevitz, Mark S.; Pollock, Kenneth H.

1995-01-01

Most change-in-ratio (CIR) methods for estimating fish and wildlife population sizes have been based only on assumptions about how encounter probabilities vary among population subclasses. When information on sampling effort is available, it is also possible to derive CIR estimators based on assumptions about how encounter probabilities vary over time. This paper presents a generalization of previous CIR models that allows explicit consideration of a range of assumptions about the variation of encounter probabilities among subclasses and over time. Explicit estimators are derived under this model for specific sets of assumptions about the encounter probabilities. Numerical methods are presented for obtaining estimators under the full range of possible assumptions. Likelihood ratio tests for these assumptions are described. Emphasis is on obtaining estimators based on assumptions about variation of encounter probabilities over time.

Role of CYP2E1 immunoglobulin G4 subclass antibodies and complement in pathogenesis of idiosyncratic drug-induced hepatitis.

PubMed

Njoku, Dolores B; Mellerson, Jenelle L; Talor, Monica V; Kerr, Douglas R; Faraday, Nauder R; Outschoorn, Ingrid; Rose, Noel R

2006-02-01

Idiosyncratic drug-induced hepatitis (IDDIH) is the third most common cause for acute liver failure in the United States. Previous studies have attempted to identify susceptible patients or early stages of disease with various degrees of success. To determine if total serum immunoglobulin subclasses, CYP2E1-specific subclass autoantibodies, complement components, or immune complexes could distinguish persons with IDDIH from others exposed to drugs, we studied persons exposed to halogenated volatile anesthetics, which have been associated with IDDIH and CYP2E1 autoantibodies. We found that patients with anesthetic-induced IDDIH had significantly elevated levels of CYP2E1-specific immunoglobulin G4 (IgG4) autoantibodies, while anesthetic-exposed healthy persons had significantly elevated levels of CYP2E1-specific IgG1 autoantibodies. Anesthetic IDDIH patients had significantly lower levels of C4a, C3a, and C5a compared to anesthetic-exposed healthy persons. C1q- and C3d-containing immune complexes were significantly elevated in anesthetic-exposed persons. In conclusion, our data suggest that anesthetic-exposed persons develop CYP2E1-specific IgG1 autoantibodies which may form detectable circulating immune complexes subsequently cleared by classical pathway activation of the complement system. Persons susceptible to anesthetic-induced IDDIH develop CYP2E1-specific IgG4 autoantibodies which form small, nonprecipitating immune complexes that escape clearance because of their size or by direct inhibition of complement activation.

Spermiogenesis and Taxonomical Values of Sperm Ultrastructures in Male Crassostrea ariakensis (Fujita & Wakiya, 1929) (Pteroirmorphia: Ostreidae) in the Estuary of the Seomjin River, Korea

PubMed Central

Son, Pal Won; Chung, Jae Seung; Kim, Jin Hee; Kim, Sung Han; Chung, Ee-Yung

2014-01-01

Characteristics of the developmental stages of spermatids during spermiogenesis and phylogenetic classicfication of the species using sperm ultrastructures in male Crassostrea ariakensis were investigated by transmission electron microscope observations. The morphology of the spermatozoon of this species has a primitive type and is similar to those of Ostreidae. Ultrastructures of mature sperms are composed of broad, modified cap-shaped acrosomal vesicle and an axial rod in subacrosomal materials on an oval nucleus, four spherical mitochondria in the sperm midpiece, and satellite fibres which appear near the distal centriole. The axoneme of the sperm tail shows a 9+2 structure. Accordingly, the ultrastructural characteristics of mature sperm of C. ariakensis resemble to those of other investigated ostreids in Ostreidae in the subclass Pteriomorphia. In this study, particularly, two transverse bands (stripes) appear at the anterior region of the acrosomal vesicle of this species, unlike two or three transverse bands (stripes) in C. gigas. It is assumed that differences in this acrosomal substructure are associated with the inability of fertilization between the genus Crassostrea and other genus species in Ostreidae. Therefore, we can use sperm ultrastructures and morphologies in the resolution of taxonomic relationships within the Ostreidae in the subclass Pteriomorphia. These spermatozoa, which contain several ultrastructures such as acrosomal vesicle, an axial rod in the sperm head part and four mitochondria and satellite fibres in the sperm midpiece, belong to the family Ostreidae in the subclass Pteriomorphia. PMID:25949188

Molecular and functional evolution of class I chitinases for plant carnivory in the caryophyllales.

PubMed

Renner, Tanya; Specht, Chelsea D

2012-10-01

Proteins produced by the large and diverse chitinase gene family are involved in the hydrolyzation of glycosidic bonds in chitin, a polymer of N-acetylglucosamines. In flowering plants, class I chitinases are important pathogenesis-related proteins, functioning in the determent of herbivory and pathogen attack by acting on insect exoskeletons and fungal cell walls. Within the carnivorous plants, two subclasses of class I chitinases have been identified to play a role in the digestion of prey. Members of these two subclasses, depending on the presence or absence of a C-terminal extension, can be secreted from specialized digestive glands found within the morphologically diverse traps that develop from carnivorous plant leaves. The degree of homology among carnivorous plant class I chitinases and the method by which these enzymes have been adapted for the carnivorous habit has yet to be elucidated. This study focuses on understanding the evolution of carnivory and chitinase genes in one of the major groups of plants that has evolved the carnivorous habit: the Caryophyllales. We recover novel class I chitinase homologs from species of genera Ancistrocladus, Dionaea, Drosera, Nepenthes, and Triphyophyllum, while also confirming the presence of two subclasses of class I chitinases based upon sequence homology and phylogenetic affinity to class I chitinases available from sequenced angiosperm genomes. We further detect residues under positive selection and reveal substitutions specific to carnivorous plant class I chitinases. These substitutions may confer functional differences as indicated by protein structure homology modeling.

Analysis of glycerophosphocholine molecular species as derivatives of 7-[(chlorocarbonyl)-methoxy]-4-methylcoumarin.

PubMed

Wheelan, P; Zirrolli, J A; Clay, K L

1992-01-01

A method has been developed for the analysis of derivatized diradylglycerols obtained from glycerophosphocholine (GPC) of transformed murine bone marrow-derived mast cells that provided high performance liquid chromatography (HPLC) separation of GPC subclasses and molecular species separation with on-line quantitation using UV detection. In addition, the derivatized diradylglycerol species were unequivocably identified by continuous flow fast-atom bombardment mass spectrometry. GPC was initially isolated by thin-layer chromatography (TLC), the phosphocholine group was hydrolyzed, and the resultant diradylglycerol was derivatized with 7-[(chlorocarbonyl)-methoxy]-4-methylcoumarin (CMMC). After separation of the derivatized subclasses by normal phase HPLC, the individual molecular species of the alkylacyl and diacyl subclasses were quantitated and collected during a subsequent reverse phase HPLC step. With an extinction coefficient of 14,700 l mol-1 cm-1 at a wavelength detection of 320 nm, the CMMC derivatives afforded sensitive UV detection (100 pmol) and quantitation of the molecular species. Continuous flow fast-atom bombardment mass spectrometry of the alkylacyl CMMC derivatives yielded abundant [MH]+ ions and a single fragment ion formed by loss of alkylketene from the sn-2 acyl group, [MH-(R = C = O)]+. No fragmentation of the sn-1 alkyl chain was observed. Diacyl derivatives also produced abundant [MH]+ ions plus two fragment ions arising from loss of RCOOH from each of the acyl substituents and two fragment ions from the loss of alkyketene from each acyl group. Individual molecular species substituents were assigned from these ions.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ramsland, Paul A.; Farrugia, William; Bradford, Tessa M.

The interaction of Abs with their specific FcRs is of primary importance in host immune effector systems involved in infection and inflammation, and are the target for immune evasion by pathogens. Fc{gamma}RIIa is a unique and the most widespread activating FcR in humans that through avid binding of immune complexes potently triggers inflammation. Polymorphisms of Fc{gamma}RIIa (high responder/low responder [HR/LR]) are linked to susceptibility to infections, autoimmune diseases, and the efficacy of therapeutic Abs. In this article, we define the three-dimensional structure of the complex between the HR (arginine, R134) allele of Fc{gamma}RIIa (Fc{gamma}RIIa-HR) and the Fc region of amore » humanized IgG1 Ab, hu3S193. The structure suggests how the HR/LR polymorphism may influence Fc{gamma}RIIa interactions with different IgG subclasses and glycoforms. In addition, mutagenesis defined the basis of the epitopes detected by FcR blocking mAbs specific for Fc{gamma}RIIa (IV.3), Fc{gamma}RIIb (X63-21), and a pan Fc{gamma}RII Ab (8.7). The epitopes detected by these Abs are distinct, but all overlap with residues defined by crystallography to contact IgG. Finally, crystal structures of LR (histidine, H134) allele of Fc{gamma}RIIa and Fc{gamma}RIIa-HR reveal two distinct receptor dimers that may represent quaternary states on the cell surface. A model is presented whereby a dimer of Fc{gamma}RIIa-HR binds Ag-Ab complexes in an arrangement that possibly occurs on the cell membrane as part of a larger signaling assembly.« less

Phenotypic and genetic diversity of chlorine-resistant Methylobacterium strains isolated from various environments.

PubMed Central

Hiraishi, A; Furuhata, K; Matsumoto, A; Koike, K A; Fukuyama, M; Tabuchi, K

1995-01-01

Strains of pink-pigmented facultative methylotrophs which were isolated previously from various environments and assigned tentatively to the genus Methylobacterium were characterized in comparison with authentic strains of previously known species of this genus. Most of the isolates derived from chlorinated water supplies exhibited resistance to chlorine, whereas 29 to 40% of the isolates from air, natural aquatic environments, and clinical materials were chlorine resistant. None of the tested authentic strains of Methylobacterium species obtained from culture collections exhibited chlorine resistance. Numerical analysis of phenotypic profiles showed that the test organisms tested were separated from each other except M. organophilum and M. rhodesianum. The chlorine-resistant isolates were randomly distributed among all clusters. The 16S ribosomal DNA (rDNA) sequence-based phylogenetic analyses showed that representatives of the isolates together with known Methylobacterium species formed a line of descent distinct from that of members of related genera in the alpha-2 subclass of the Proteobacteria and were divided into three subclusters within the Methylobacterium group. These results demonstrate that there is phenotypic and genetic diversity among chlorine-resistant Methylobacterium strains within the genus. PMID:7793931

Comprehensive characterization of phenolic and other polar compounds in the seed and seed coat of avocado by HPLC-DAD-ESI-QTOF-MS.

PubMed

Figueroa, Jorge G; Borrás-Linares, Isabel; Lozano-Sánchez, Jesús; Segura-Carretero, Antonio

2018-03-01

Avocado seed and seed coat are important by-products from avocado industrialization, with important functional properties. The aim of the present study was to determine the phenolic profile and other polar compounds of avocado seed and seed coat using accelerated solvent extraction (ASE) and liquid chromatography coupled to Ultra-High-Definition Accurate-Mass Q-TOF. In this research 84 compounds were identified, within eight subclass group, among these 45 phenolic compounds were identified for first time in avocado seed. Condensed tannins, phenolic acids and flavonoids were the most representative groups in both samples. As far as we are concerned, this is the first time that avocado seed coat has been studied regarding its phenolic compounds using such a powerful instrumental technique. In addition, the radical-scavenging activities were analysed in order to estimate the antioxidant potential of extracts. These results point out that avocado seed and seed coat constitute a source of bioactive ingredients for its use in the food, cosmetic or pharmaceutical sector. Copyright © 2017 Elsevier Ltd. All rights reserved.

Population diversity of ammonium oxidizers investigated by specific PCR amplification

USGS Publications Warehouse

Ward, B.B.; Voytek, M.A.; Witzel, K.-P.

1997-01-01

The species composition of ammonia-oxidizing bacteria in aquatic environments was investigated using PCR primers for 16S rRNA genes to amplify specific subsets of the total ammonia-oxidizer population. The specificity of the amplification reactions was determined using total genomic DNA from known nitrifying strains and non-nitrifying strains identified as having similar rDNA sequences. Specificity of amplification was determined both for direct amplification, using the nitrifier specific primers, and with nested amplification, in which the nitrifier primers were used to reamplify a fragment obtained from direct amplification with Eubacterial universal primers. The present level of specificity allows the distinction between Nitrosomonas europaea, Nitrosomonas sp. (marine) and the other known ammonia-oxidizers in the beta subclass of the Proteobacteria. Using total DNA extracted from natural samples, we used direct amplification to determine presence/absence of different species groups. Species composition was found to differ among depths in vertical profiles of lake samples and among samples and enrichments from various other aquatic environments. Nested PCR yielded several more positive reactions, which implies that nitrifier DNA was present in most samples, but often at very low levels.

Evaluation of post-surgical cognitive function and protein fingerprints in the cerebro-spinal fluid utilizing surface-enhanced laser Desorption/Ionization time-of-flight mass-spectrometry (SELDI-TOF MS) after coronary artery bypass grafting: review of proteomic analytic tools and introducing a new syndrome.

PubMed

Reis, H J; Wang, L; Verano-Braga, T; Pimenta, A M C; Kálmán, J; Bogáts, G; Babik, B; Vieira, L B; Teixeira, A L; Mukhamedyarov, M A; Zefirov, A L; Kiyasov, A P; Rizvanov, A A; Matin, K; Palotás, M; Guimarães, M M; Ferreira, C N; Yalvaç, M E; Janka, Z; Palotás, A

2011-01-01

Cognitive dysfunction following surgery is a common complication, which increases the incidence of other co-morbid conditions, hospital and health-care costs. The reported rate of the occurrence of post-operative cognitive decline varies with different studies, depending on population profile, type of surgery, definition of cognitive disorder and detection methods, design of study, etc. It remains unclear whether these psychiatric signs and symptoms are direct results of the effects of surgery or general anesthesia. Nonetheless they are more frequent after cardiac surgery and are likely to be multi-factorial, but the patho-mechanisms are not yet fully characterized. This communication provides a synopsis of proteomics tools and delineates novel SELDI-TOF results to evaluate biomarkers in this regard. Presented for the first time is a classification of the clinically relevant forms of post-operative cognitive decline with the advent of a novel subclass.

The effect of various zinc binding groups on inhibition of histone deacetylases 1-11.

PubMed

Madsen, Andreas S; Kristensen, Helle M E; Lanz, Gyrithe; Olsen, Christian A

2014-03-01

Histone deacetylases (HDACs) have the ability to cleave the acetyl groups of ε-N-acetylated lysine residues in a variety of proteins. Given that human cells contain thousands of different acetylated lysine residues, HDACS may regulate a wide variety of processes including some implicated in conditions such as cancer and neurodegenerative disorders. Herein we report the synthesis and in vitro biochemical profiling of a series of compounds, including known inhibitors as well as novel chemotypes, that incorporate putative new zinc binding domains. By evaluating the compound collection against all 11 recombinant human HDACs, we found that the trifluoromethyl ketone functionality provides potent inhibition of all four subclasses of the Zn(2+) -dependent HDACs. Potent inhibition was observed with two different scaffolds, demonstrating the efficiency of the trifluoromethyl ketone moiety as a zinc binding motif. Interestingly, we also identified silanediol as a zinc binding group with potential for future development of non-hydroxamate class I and class IIb HDAC inhibitors. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Phenotypic and genetic diversity of chlorine-resistant Methylobacterium strains isolated from various environments.

PubMed

Hiraishi, A; Furuhata, K; Matsumoto, A; Koike, K A; Fukuyama, M; Tabuchi, K

1995-06-01

Strains of pink-pigmented facultative methylotrophs which were isolated previously from various environments and assigned tentatively to the genus Methylobacterium were characterized in comparison with authentic strains of previously known species of this genus. Most of the isolates derived from chlorinated water supplies exhibited resistance to chlorine, whereas 29 to 40% of the isolates from air, natural aquatic environments, and clinical materials were chlorine resistant. None of the tested authentic strains of Methylobacterium species obtained from culture collections exhibited chlorine resistance. Numerical analysis of phenotypic profiles showed that the test organisms tested were separated from each other except M. organophilum and M. rhodesianum. The chlorine-resistant isolates were randomly distributed among all clusters. The 16S ribosomal DNA (rDNA) sequence-based phylogenetic analyses showed that representatives of the isolates together with known Methylobacterium species formed a line of descent distinct from that of members of related genera in the alpha-2 subclass of the Proteobacteria and were divided into three subclusters within the Methylobacterium group. These results demonstrate that there is phenotypic and genetic diversity among chlorine-resistant Methylobacterium strains within the genus.

21 CFR 866.5220 - Cohn fraction II immunolog-ical test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... of plasma containing protein gamma globulins, predominantly of the IgG class. The device may be used... subclasses, and to reduce nonspecific adsorption of plasma proteins in immunoassay techniques. Measurement of...

21 CFR 866.5220 - Cohn fraction II immunolog-ical test system.

Code of Federal Regulations, 2012 CFR

2012-04-01

... of plasma containing protein gamma globulins, predominantly of the IgG class. The device may be used... subclasses, and to reduce nonspecific adsorption of plasma proteins in immunoassay techniques. Measurement of...

21 CFR 866.5220 - Cohn fraction II immunolog-ical test system.

Code of Federal Regulations, 2011 CFR

2011-04-01

... of plasma containing protein gamma globulins, predominantly of the IgG class. The device may be used... subclasses, and to reduce nonspecific adsorption of plasma proteins in immunoassay techniques. Measurement of...

21 CFR 866.5220 - Cohn fraction II immunolog-ical test system.

Code of Federal Regulations, 2013 CFR

2013-04-01

... of plasma containing protein gamma globulins, predominantly of the IgG class. The device may be used... subclasses, and to reduce nonspecific adsorption of plasma proteins in immunoassay techniques. Measurement of...

21 CFR 866.5220 - Cohn fraction II immunolog-ical test system.

Code of Federal Regulations, 2014 CFR

2014-04-01

... of plasma containing protein gamma globulins, predominantly of the IgG class. The device may be used... subclasses, and to reduce nonspecific adsorption of plasma proteins in immunoassay techniques. Measurement of...

40 CFR 86.1103-87 - Criteria for availability of nonconformance penalties.

Code of Federal Regulations, 2010 CFR

2010-07-01

... (CONTINUED) Nonconformance Penalties for Gasoline-Fueled and Diesel Heavy-Duty Engines and Heavy-Duty.... (a) EPA shall establish for each subclass of heavy-duty engines and heavy-duty vehicles (other than...

40 CFR 86.1104-91 - Determination of upper limits.

Code of Federal Regulations, 2010 CFR

2010-07-01

...) Nonconformance Penalties for Gasoline-Fueled and Diesel Heavy-Duty Engines and Heavy-Duty Vehicles, Including... pollutant emission standard for a subclass of heavy-duty engines or heavy-duty vehicles for which an NCP is...

Annelida, Euhirudinea (leeches)

EPA Science Inventory

Worldwide, there are over 600 species of leeches described which occur in freshwater, marine, estuarine, and moist-terrestrial ecosystems. Leeches are included in the Class Clitellata, Subclass Hirudinida, and Superorder Euhirudinea. Seven of the ten families of leeches occur in...

GRB070610: A Curious Galactic Transient

NASA Technical Reports Server (NTRS)

Kasliwal, M. M.; Kulkrarni. S. R.; Cameron, P. B.; Nakar, E.; Ofek, E. O.; Rau, A.; Soderberg, A. M.; Campana, S.; Bloom, J. S.; Perley, D. A.;

GRB 070610: A Curious Galactic Transient

NASA Astrophysics Data System (ADS)

Kasliwal, M. M.; Cenko, S. B.; Kulkarni, S. R.; Cameron, P. B.; Nakar, E.; Ofek, E. O.; Rau, A.; Soderberg, A. M.; Campana, S.; Bloom, J. S.; Perley, D. A.; Pollack, L. K.; Barthelmy, S.; Cummings, J.; Gehrels, N.; Krimm, H. A.; Markwardt, C. B.; Sato, G.; Chandra, P.; Frail, D.; Fox, D. B.; Price, P. A.; Berger, E.; Grebenev, S. A.; Krivonos, R. A.; Sunyaev, R. A.

2008-05-01

GRB 070610 is a typical high-energy event with a duration of 5 s. Yet within the burst localization we detect a highly unusual X-ray and optical transient, Swift J195509.6+261406. We see high-amplitude X-ray and optical variability on very short timescales even at late times. Using near-infrared imaging assisted by a laser guide star and adaptive optics, we identified the counterpart of Swift J195509.6+261406. Late-time optical and near-infrared imaging constrain the spectral type of the counterpart to be fainter than a K-dwarf, assuming it is of Galactic origin. It is possible that GRB 070610 and Swift J195509.6+261406 are unrelated sources. However, the absence of a typical X-ray afterglow from GRB 070610 in conjunction with the spatial and temporal coincidence of the two motivate us to suggest that the sources are related. The closest (imperfect) analog to Swift J195509.6+261406 is V4641 Sgr, an unusual black hole binary. We suggest that Swift J195509.6+261406 along with V4641 Sgr define a subclass of stellar black hole binaries—the fast X-ray novae. We further suggest that fast X-ray novae are associated with bursts of gamma rays. If so, GRB 070610 defines a new class of celestial gamma-ray bursts and these bursts dominate the long-duration GRB demographics.

Profiling Instructional Effectiveness to Reveal Its Relationship to Learning

ERIC Educational Resources Information Center

Kalender, Ilker

2014-01-01

The purpose of the present study is to define instructional profiles and investigate the relationship between these profiles and learning indicators such as end-of-semester grades and self-reported amount of learning. Instructional profiles were obtained using a segmentation method. Student ratings were used as indicators of instructional…

Spectral emission measurement of igneous rocks using a spectroradiometer

NASA Technical Reports Server (NTRS)

Hunton, W. D.

1970-01-01

Spectroradiometer is used for either close or remote identification of rocks not heated to high temperatures. Instrument yields reproducible data spectra with excellent signal-to-noise ratios and readily identifiable spectral details, including differences in subclasses.

Pathway-based personalized analysis of cancer

PubMed Central

Drier, Yotam; Sheffer, Michal; Domany, Eytan

2013-01-01

We introduce Pathifier, an algorithm that infers pathway deregulation scores for each tumor sample on the basis of expression data. This score is determined, in a context-specific manner, for every particular dataset and type of cancer that is being investigated. The algorithm transforms gene-level information into pathway-level information, generating a compact and biologically relevant representation of each sample. We demonstrate the algorithm’s performance on three colorectal cancer datasets and two glioblastoma multiforme datasets and show that our multipathway-based representation is reproducible, preserves much of the original information, and allows inference of complex biologically significant information. We discovered several pathways that were significantly associated with survival of glioblastoma patients and two whose scores are predictive of survival in colorectal cancer: CXCR3-mediated signaling and oxidative phosphorylation. We also identified a subclass of proneural and neural glioblastoma with significantly better survival, and an EGF receptor-deregulated subclass of colon cancers. PMID:23547110

Subnanomolar indazole-5-carboxamide inhibitors of monoamine oxidase B (MAO-B) continued: indications of iron binding, experimental evidence for optimised solubility and brain penetration.

PubMed

Tzvetkov, Nikolay T; Antonov, Liudmil

2017-12-01

Pharmacological and physicochemical studies of N-unsubstituted indazole-5-carboxamides (subclass I) and their structurally optimised N1-methylated analogues (subclass II), initially developed as drug and radioligand candidates for the treatment and diagnosis of Parkinson's disease (PD), are presented. The compounds are highly brain permeable, selective, reversible, and competitive monoamine oxidase B (MAO-B) inhibitors with improved water-solubility and subnanomolar potency (pIC 50  >8.8). Using a well-validated, combined X-ray/modelling technology platform, we performed a semi-quantitative analysis of the binding modes of all compounds and investigated the role of the indazole N1 position for their MAO-B inhibitory activity. Moreover, compounds NTZ-1006, 1032, and 1441 were investigated for their ability to bind Fe 2+ and Fe 3+ ions using UV-visible spectroscopy.

Multiple subclasses of Purkinje cells in the primate floccular complex provide similar signals to guide learning in the vestibulo-ocular reflex

NASA Technical Reports Server (NTRS)

Raymond, J. L.; Lisberger, S. G.

1997-01-01

The neural "learning rules" governing the induction of plasticity in the cerebellum were analyzed by recording the patterns of neural activity in awake, behaving animals during stimuli that induce a form of cerebellum-dependent learning. We recorded the simple- and complex-spike responses of a broad sample of Purkinje cells in the floccular complex during a number of stimulus conditions that induce motor learning in the vestibulo-ocular reflex (VOR). Each subclass of Purkinje cells carried essentially the same information about required changes in the gain of the VOR. The correlation of simple-spike activity in Purkinje cells with activity in vestibular pathways could guide learning during low-frequency but not high-frequency stimuli. Climbing fiber activity could guide learning during all stimuli tested but only if compared with the activity present approximately 100 msec earlier in either vestibular pathways or Purkinje cells.

[Cholesterol of the high-density lipoprotein subclasses in the native inhabitants of the Chukchi National Autonomous Okrug].

PubMed

Polesskiĭ, V A; Chepurnenko, N V; Koshechkin, V A; Morozov, V V; Gerasimova, E N

1980-12-01

The authors studied the content of total cholesterol (Ch), triglycerides (TG), CS of high density lipoprotein (HDL2 and HDL3) subclasses and testosterone in blood plasma of 30-59-year-old males, natives or newcomers of Chukotsk, and compared the results with the corresponding values determined in the male population of Moscow. It was established that the mean HDL Ch concentration in blood plasma was higher and the content of TG and to a lesser degree that of total CS, was lower in the Chukchi males than in the male Moscow population and in the newcomers who were examined. It was also shown that in hypo- and hyper-alphalipoproteinemia in all groups examined, the content of HDL2 Ch changed for the most part (decreased or increased, respectively) while the level of HDL3 Ch remained relatively stable.

Mammalian diversity: gametes, embryos and reproduction.

PubMed

Behringer, Richard R; Eakin, Guy S; Renfree, Marilyn B

2006-01-01

The class Mammalia is composed of approximately 4800 extant species. These mammalian species are divided into three subclasses that include the monotremes, marsupials and eutherians. Monotremes are remarkable because these mammals are born from eggs laid outside of the mother's body. Marsupial mammals have relatively short gestation periods and give birth to highly altricial young that continue a significant amount of 'fetal' development after birth, supported by a highly sophisticated lactation. Less than 10% of mammalian species are monotremes or marsupials, so the great majority of mammals are grouped into the subclass Eutheria, including mouse and human. Mammals exhibit great variety in morphology, physiology and reproduction. In the present article, we highlight some of this remarkable diversity relative to the mouse, one of the most widely used mammalian model organisms, and human. This diversity creates challenges and opportunities for gamete and embryo collection, culture and transfer technologies.

Accidental inflation from Kähler uplifting

NASA Astrophysics Data System (ADS)

Ben-Dayan, Ido; Jing, Shenglin; Westphal, Alexander; Wieck, Clemens

2014-03-01

We analyze the possibility of realizing inflation with a subsequent dS vacuum in the Käahler uplifting scenario. The inclusion of several quantum corrections to the 4d effective action evades previous no-go theorems and allows for construction of simple and successful models of string inflation. The predictions of several benchmark models are in accord with current observations, i.e., a red spectral index, negligible non-gaussianity, and spectral distortions similar to the simplest models of inflation. A particularly interesting subclass of models are ``left-rolling" ones, where the overall volume of the compactified dimensions shrinks during inflation. We call this phenomenon ``inflation by deflation" (IBD), where deflation refers to the internal manifold. This subclass has the appealing features of being insensitive to initial conditions, avoiding the overshooting problem, and allowing for observable running α ~ 0.012 and enhanced tensor-to-scalar ratio r ~ 10-5. The latter results differ significantly from many string inflation models.

A CATALOG OF SOLAR X-RAY PLASMA EJECTIONS OBSERVED BY THE SOFT X-RAY TELESCOPE ON BOARD YOHKOH

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tomczak, M.; Chmielewska, E., E-mail: tomczak@astro.uni.wroc.pl, E-mail: chmielewska@astro.uni.wroc.pl

2012-03-01

A catalog of X-ray plasma ejections (XPEs) observed by the Soft X-ray Telescope on board the Yohkoh satellite has been recently developed in the Astronomical Institute of University of Wroclaw. The catalog contains records of 368 events observed in years 1991-2001 including movies and cross-references to associated events like flares and coronal mass ejections (CMEs). One hundred sixty-three XPEs out of 368 in the catalog were not reported until now. A new classification scheme of XPEs is proposed in which morphology, kinematics, and recurrence are considered. The relation between individual subclasses of XPEs and the associated events was investigated. Themore » results confirm that XPEs are strongly inhomogeneous, responding to different processes that occur in the solar corona. A subclass of erupting loop-like XPEs is a promising candidate to be a high-temperature precursor of CMEs.« less

B1-Metallo-beta-Lactamases: Where do we stand?

PubMed Central

Mojica, Maria F.; Bonomo, Robert A.; Fast, Walter

2015-01-01

Metallo-beta-Lactamases (MBLs) are class B β-lactamases that hydrolyze almost all clinically-available β-lactam antibiotics. MBLs feature the distinctive αβ/βα sandwich fold of the metallo-hydrolase / oxidoreductase superfamily and possess a shallow active-site groove containing one or two divalent zinc ions, flanked by flexible loops. According to sequence identity and zinc ion dependence, MBLs are classified into three subclasses (B1, B2 and B3), of which the B1 subclass enzymes have emerged as the most clinically significant. Differences among the active site architectures, the nature of zinc ligands, and the catalytic mechanisms have limited the development of a common inhibitor. In this review, we will describe the molecular epidemiology and structural studies of the most prominent representatives of class B1 MBLs (NDM-1, IMP-1 and VIM-2) and describe the implications for inhibitor design to counter this growing clinical threat. PMID:26424398

Mercaptoheterocyclic ligands grafted on a poly(ethylene vinyl alcohol) membrane for the purification of immunoglobulin G in a salt independent thiophilic chromatography.

PubMed

Coffinier, Yannick; Vijayalakshmi, Mookambeswaran A

2004-08-25

In this study, we attempted a limited combinatorial approach for designing affinity ligands based on mercaptoheterocyclic components. The template, divinyl sulfone structure (DVS), which was grafted on poly(ethylene vinyl alcohol) (PEVA) hollow fiber membrane, has served for the tethering of different heterocyclic compounds as pyridine, imidazole, purine and pyrimidine rings. Their ability to adsorb specifically IgG in a salt independent manner out of pure IgG solution, mixture of IgG/albumin and human plasma was demonstrated. Mercapto methyl imidazole (MMI) has shown the best adsorption of IgG in terms of binding capacity. No subclass discrimination was observed on all tested ligands except for mercapto methyl pyrimidine where the major IgG subclass adsorbed was IgG3. MMI gave an IgG binding capacity of 100 microg/cm2 of hollow fiber membrane surface area.

Biochemical Characterization, Action on Macrophages, and Superoxide Anion Production of Four Basic Phospholipases A2 from Panamanian Bothrops asper Snake Venom

PubMed Central

Rueda, Aristides Quintero; Rodríguez, Isela González; Arantes, Eliane C.; Setúbal, Sulamita S.; Calderon, Leonardo de A.; Zuliani, Juliana P.; Stábeli, Rodrigo G.; Soares, Andreimar M.

2013-01-01

Bothrops asper (Squamata: Viperidae) is the most important venomous snake in Central America, being responsible for the majority of snakebite accidents. Four basic PLA2s (pMTX-I to -IV) were purified from crude venom by a single-step chromatography using a CM-Sepharose ion-exchange column (1.5 × 15 cm). Analysis of the N-terminal sequence demonstrated that pMTX-I and III belong to the catalytically active Asp49 phospholipase A2 subclass, whereas pMTX-II and IV belong to the enzymatically inactive Lys49 PLA2s-like subclass. The PLA2s isolated from Panama Bothrops asper venom (pMTX-I, II, III, and IV) are able to induce myotoxic activity, inflammatory reaction mainly leukocyte migration to the muscle, and induce J774A.1 macrophages activation to start phagocytic activity and superoxide production. PMID:23509779

Lovelock branes

NASA Astrophysics Data System (ADS)

Kastor, David; Ray, Sourya; Traschen, Jennie

2017-10-01

We study the problem of finding brane-like solutions to Lovelock gravity, adopting a general approach to establish conditions that a lower dimensional base metric must satisfy in order that a solution to a given Lovelock theory can be constructed in one higher dimension. We find that for Lovelock theories with generic values of the coupling constants, the Lovelock tensors (higher curvature generalizations of the Einstein tensor) of the base metric must all be proportional to the metric. Hence, allowed base metrics form a subclass of Einstein metrics. This subclass includes so-called ‘universal metrics’, which have been previously investigated as solutions to quantum-corrected field equations. For specially tuned values of the Lovelock couplings, we find that the Lovelock tensors of the base metric need to satisfy fewer constraints. For example, for Lovelock theories with a unique vacuum there is only a single such constraint, a case previously identified in the literature, and brane solutions can be straightforwardly constructed.

[The taxonomic rank and place of Colpodellida in the system of the Protista].

PubMed

Myl'nikov, A P; Krylov, M V; Frolov, A O

2000-01-01

The analysis of ultrastructure organisation and divergent processes in Colpodellida, Perkinsida, Gregarinea and Coccidea has confirmed the presence of unique basic structures in all of these organisms and the necessity to combine them into the single phylum Sporozoa. A taxonomic rank and place of Colpodellida in the system of living organisms is represented as follows: phylum Sporozoa Leuckart, 1879; em. Krylov, Mylnikov, 1986. (Syn.: Apicomplexa Levine, 1970). Predators or parasites. Common basic structure: pellicular membranes, subpellicular microtubules, micropores, conoid, rhoptries and micronemes, tubular mitochondrial cristae. Class Perkinsea Levine, 1978. Predators or parasites, vegetative stages with two heterodynamic flagella. Subclass 1. Colpodellia nom. nov. (Syn.: Spiromonadia Krylov, Mylnikov, 1986). Predators, two heterodynamic flagella with string-like mastigonemes (if present), division is exclusively within a cyst, with 2-4 daughter cells being produced, extrusomes are trichocyst-like. Subclass 2. Perkinsia Levine, 1978. Parasites, zoospores with two heterodynamic flagella, mastigonemes (if present) bristle-like or string-like.

Differential expression of poplar sucrose nonfermenting1-related protein kinase 2 genes in response to abiotic stress and abscisic acid.

PubMed

Yu, Xiang; Takebayashi, Arika; Demura, Taku; Ohtani, Misato

2017-09-01

Knowledge on the responses of woody plants to abiotic stress can inform strategies to breed improved tree varieties and to manage tree species for environmental conservation and the production of lignocellulosic biomass. In this study, we examined the expression patterns of poplar (Populus trichocarpa) genes encoding members of the sucrose nonfermenting1-related protein kinase 2 (SnRK2) family, which are core components of the abiotic stress response. The P. trichocarpa genome contains twelve SnRK2 genes (PtSnRK2.1- PtSnRK2.12) that can be divided into three subclasses (I-III) based on the structures of their encoded kinase domains. We found that PtSnRK2s are differentially expressed in various organs. In MS medium-grown plants, all of the PtSnRK2 genes were significantly upregulated in response to abscisic acid (ABA) treatment, whereas osmotic and salt stress treatments induced only some (four and seven, respectively) of the PtSnRK2 genes. By contrast, soil-grown plants showed increased expression of most PtSnRK2 genes under drought and salt treatments, but not under ABA treatment. In soil-grown plants, drought stress induced SnRK2 subclass II genes in all tested organs (leaves, stems, and roots), whereas subclass III genes tended to be upregulated in leaves only. These results suggest that the PtSnRK2 genes are involved in abiotic stress responses, are at least partially activated by ABA, and show organ-specific responses.

Carbon-enhanced metal-poor stars: CEMP-s and CEMP-no subclasses in the halo system of the Milky Way

DOE Office of Scientific and Technical Information (OSTI.GOV)

Carollo, Daniela; Freeman, Ken; Beers, Timothy C.

2014-06-20

We explore the kinematics and orbital properties of a sample of 323 very metal-poor stars in the halo system of the Milky Way, selected from the high-resolution spectroscopic follow-up studies of Aoki et al. and Yong et al. The combined sample contains a significant fraction of carbon-enhanced metal-poor (CEMP) stars (22% or 29%, depending on whether a strict or relaxed criterion is applied for this definition). Barium abundances (or upper limits) are available for the great majority of the CEMP stars, allowing for their separation into the CEMP-s and CEMP-no subclasses. A new method to assign membership to the inner-more » and outer-halo populations of the Milky Way is developed, making use of the integrals of motion, and applied to determine the relative fractions of CEMP stars in these two subclasses for each halo component. Although limited by small-number statistics, the data suggest that the inner halo of the Milky Way exhibits a somewhat higher relative number of CEMP-s stars than CEMP-no stars (57% versus 43%), while the outer halo possesses a clearly higher fraction of CEMP-no stars than CEMP-s stars (70% versus 30%). Although larger samples of CEMP stars with known Ba abundances are required, this result suggests that the dominant progenitors of CEMP stars in the two halo components were different; massive stars for the outer halo, and intermediate-mass stars in the case of the inner halo.« less

Anti-desmoglein 1 antibodies in Tunisian healthy subjects: arguments for the role of environmental factors in the occurrence of Tunisian pemphigus foliaceus

PubMed Central

KALLEL SELLAMI, M; BEN AYED, M; MOUQUET, H; DROUOT, L; ZITOUNI, M; MOKNI, M; CERRUTI, M; TURKI, H; FEZZA, B; MOKHTAR, I; BEN OSMAN, A; ZAHAF, A; KAMOUN, M R; JOLY, P; MASMOUDI, H; MAKNI, S; TRON, F; GILBERT, D

2004-01-01

Pemphigus foliaceus is an autoimmune blistering skin disease mediated by autoantibodies directed against desmoglein 1 and occurs as a sporadic form throughout the world, or as an endemic form called fogo selvagem in Brazil. Healthy subjects living in Brazilian endemic areas produce antidesmoglein 1 antibodies, suggesting the role of environmental factors in the initiation of the autoimmune response. Tunisia was described recently as an endemic area where the disease is characterized by its high rate among young people, especially women. An enzyme-linked immunosorbent assay using recombinant desmoglein 1 as antigen was used to detect antibodies against desmoglein 1 and calibrated with sera from 67 French healthy blood donors, 20 French pemphigus foliaceus patients and patients with other bullous skin diseases. When sera from 179 healthy Tunisian blood donors were tested, 31 (17%) were found positive. The desmoglein 1 binding activity of these 31 sera was confirmed in 10 cases by indirect immunofluorescence analysis and/or immunoblotting using human epidermal extract. Subclass analysis of antidesmoglein 1 antibodies showed that they were almost exclusively of the IgG2 subclass in positive normal sera and of IgG4 subclass in patients with PF. Thus, antibodies against desmoglein 1 are prevalent in normal subjects living in Tunisia which, along with their IgG2 isotype, suggests the role of the environment in the pathogenesis of this endemic type of pemphigus foliaceus and the need for additional factors to switch from a subclinical to a clinical form of the disease. PMID:15196262

Hypogammaglobulinemia associated with accelerated catabolism of IgG secondary to its interaction with an IgG-reactive monoclonal IgM

PubMed Central

Waldmann, Thomas A.; Johnson, John S.; Talal, Norman

1971-01-01

Hypogammaglobulinemia due to a new pathophysiological mechanism was studied in a patient with Sjögren's syndrome, a monoclonal IgM and a mixed (IgM-IgG) cryoglobulinemia. The IgM (IgMdk) component of the cryogel possessed light chains of λ-type with highly restricted electrophoretic mobility analagous to those of a Waldenström's macroglobulin. IgMdk reacted specifically with native IgG, with IgG subclasses 1, 2, and 4, and with the Fc piece of IgG to form a cryogel. Serum concentrations of IgG 1, 2, and 4 were 10% of normal, whereas the IgG3 level was slightly increased and the IgM level was markedly increased. Viscosity and analytical ultracentrifugation studies with the purified mixed cryogel (IgM-LgG) indicated soluble complex formation over a temperature range (36-38°C) attainable in vivo. Immunoglobulin turnover studies revealed a markedly elevated rate of IgM synthesis with a normal survival of IgM, IgA, and IgE. IgG3, which failed to form complexes with IgMdk at body temperature, had a normal synthetic rate and survival. In contrast, the other IgG subclasses showed reduced synthesis and shortened survival. These studies are the first indicating a short survival of some IgG subclasses with a normal survival of another. The hypogammaglobulinemia appears to be due in part to a new mechanism of accelerated protein catabolism: The rapid elimination of IgG due to its interaction with an IgG-reactive monoclonal IgM. PMID:4993860

A Structure-Based Classification of Class A β-Lactamases, a Broadly Diverse Family of Enzymes

PubMed Central

Slama, Patrick; Dény, Paul; Labia, Roger

2015-01-01

SUMMARY For medical biologists, sequencing has become a commonplace technique to support diagnosis. Rapid changes in this field have led to the generation of large amounts of data, which are not always correctly listed in databases. This is particularly true for data concerning class A β-lactamases, a group of key antibiotic resistance enzymes produced by bacteria. Many genomes have been reported to contain putative β-lactamase genes, which can be compared with representative types. We analyzed several hundred amino acid sequences of class A β-lactamase enzymes for phylogenic relationships, the presence of specific residues, and cluster patterns. A clear distinction was first made between dd-peptidases and class A enzymes based on a small number of residues (S70, K73, P107, 130SDN132, G144, E166, 234K/R, 235T/S, and 236G [Ambler numbering]). Other residues clearly separated two main branches, which we named subclasses A1 and A2. Various clusters were identified on the major branch (subclass A1) on the basis of signature residues associated with catalytic properties (e.g., limited-spectrum β-lactamases, extended-spectrum β-lactamases, and carbapenemases). For subclass A2 enzymes (e.g., CfxA, CIA-1, CME-1, PER-1, and VEB-1), 43 conserved residues were characterized, and several significant insertions were detected. This diversity in the amino acid sequences of β-lactamases must be taken into account to ensure that new enzymes are accurately identified. However, with the exception of PER types, this diversity is poorly represented in existing X-ray crystallographic data. PMID:26511485

Multigene-based analyses on evolutionary phylogeny of two controversial ciliate orders: Pleuronematida and Loxocephalida (Protista, Ciliophora, Oligohymenophorea).

PubMed

Gao, Feng; Katz, Laura A; Song, Weibo

2013-07-01

Relationships among members of the ciliate subclass Scuticociliatia (Ciliophora, Oligohymenophorea) are largely unresolved. Phylogenetic studies of its orders Pleuronematida and Loxocephalida were initially based on small subunit ribosomal RNA gene (SSU-rDNA) analyses of a limited number of taxa. Here we characterized 37 sequences (SSU-rDNA, ITS-5.8S and LSU-rDNA) from 21 taxonomically controversial members of these orders. Phylogenetic trees constructed to assess the inter- and intra-generic relationships of pleuronematids and loxocephalids reveal the following: (1) the order Loxocephalida and its two families Loxocephalidae and Cinetochilidae are not monophyletic when more taxa are added; (2) the core pleuronematids are divided into two fully supported clades, however, the order Pleuronematida is not monophyletic because Cyclidium glaucoma is closer to Thigmotrichida; (3) the family Pleuronematidae and the genus Schizocalyptra are monophyletic, though rDNA sequences of Pleuronema species are highly variable; (4) Pseudoplatynematum and Sathrophilus are closely related to the subclass Astomatia, while Cinetochilum forms a monophyletic group with the subclass Apostomatia; and (5) Hippocomos falls in the order Pleuronematida and is closely related to Eurystomatellidae and Cyclidium plouneouri. Further, in an effort to provide a better resolution of evolutionary relationships, the secondary structures of ITS2 transcripts and the variable region 4 (V4) of the small subunit ribosomal RNA (SSU-rRNA) are predicted, revealing that ITS2 structures are conserved at the order level while V4 region structures are more variable than ITS2 structures. Copyright © 2013 Elsevier Inc. All rights reserved.

Growth of chitinolytic dune soil beta-subclass Proteobacteria in response to invading fungal hyphae.

PubMed

De Boer, W; Klein Gunnewiek, P J; Kowalchuk, G A; Van Veen, J A

2001-08-01

It has frequently been reported that chitinolytic soil bacteria, in particular biocontrol strains, can lyse living fungal hyphae, thereby releasing potential growth substrate. However, the conditions used in such assays (high bacterial density, rich media, fragmented hyphae) make it difficult to determine whether mycolytic activity is actually of importance for the growth and survival of chitinolytic bacteria in soils. An unidentified group of beta-subclass Proteobacteria (CbetaPs) was most dominant among the culturable nonfilamentous chitinolytic bacteria isolated from Dutch sand dune soils. Here we demonstrate that the CbetaPs grew at the expense of extending fungal mycelium of three dune soil fungi (Chaetomium globosum, Fusarium culmorum, and Mucor hiemalis) under nutrient-limiting, soil-like conditions. Aggregates of CbetaPs were also often found attached to fungal hyphae. The growth of a control group of dominant nonchitinolytic dune soil bacteria (beta- and gamma-subclass Proteobacteria) was not stimulated in the mycelial zone, indicating that growth-supporting materials were not independently released in appreciable amounts by the extending hyphae. Therefore, mycolytic activities of CbetaPs have apparently been involved in allowing them to grow after exposure to living hyphae. The chitinase inhibitor allosamidin did not, in the case of Mucor, or only partially, in the cases of Chaetomium and Fusarium, repress mycolytic growth of the CbetaPs, indicating that chitinase activity alone could not explain the extent of bacterial proliferation. Chitinolytic Stenotrophomonas-like and Cytophaga-like bacteria, isolated from the same dune soils, were only slightly stimulated by exposure to fungal hyphae.

Role of CYP2E1 Immunoglobulin G4 Subclass Antibodies and Complement in Pathogenesis of Idiosyncratic Drug-Induced Hepatitis

PubMed Central

Njoku, Dolores B.; Mellerson, Jenelle L.; Talor, Monica V.; Kerr, Douglas R.; Faraday, Nauder R.; Outschoorn, Ingrid; Rose, Noel R.

2006-01-01

Idiosyncratic drug-induced hepatitis (IDDIH) is the third most common cause for acute liver failure in the United States. Previous studies have attempted to identify susceptible patients or early stages of disease with various degrees of success. To determine if total serum immunoglobulin subclasses, CYP2E1-specific subclass autoantibodies, complement components, or immune complexes could distinguish persons with IDDIH from others exposed to drugs, we studied persons exposed to halogenated volatile anesthetics, which have been associated with IDDIH and CYP2E1 autoantibodies. We found that patients with anesthetic-induced IDDIH had significantly elevated levels of CYP2E1-specific immunoglobulin G4 (IgG4) autoantibodies, while anesthetic-exposed healthy persons had significantly elevated levels of CYP2E1-specific IgG1 autoantibodies. Anesthetic IDDIH patients had significantly lower levels of C4a, C3a, and C5a compared to anesthetic-exposed healthy persons. C1q- and C3d-containing immune complexes were significantly elevated in anesthetic-exposed persons. In conclusion, our data suggest that anesthetic-exposed persons develop CYP2E1-specific IgG1 autoantibodies which may form detectable circulating immune complexes subsequently cleared by classical pathway activation of the complement system. Persons susceptible to anesthetic-induced IDDIH develop CYP2E1-specific IgG4 autoantibodies which form small, nonprecipitating immune complexes that escape clearance because of their size or by direct inhibition of complement activation. PMID:16467335

Conceptual design of high speed supersonic aircraft: A brief review on SR-71 (Blackbird) aircraft

NASA Astrophysics Data System (ADS)

Xue, Hui; Khawaja, H.; Moatamedi, M.

2014-12-01

The paper presents the conceptual design of high-speed supersonic aircraft. The study focuses on SR-71 (Blackbird) aircraft. The input to the conceptual design is a mission profile. Mission profile is a flight profile of the aircraft defined by the customer. This paper gives the SR-71 aircraft mission profile specified by US air force. Mission profile helps in defining the attributes the aircraft such as wing profile, vertical tail configuration, propulsion system, etc. Wing profile and vertical tail configurations have direct impact on lift, drag, stability, performance and maneuverability of the aircraft. A propulsion system directly influences the performance of the aircraft. By combining the wing profile and the propulsion system, two important parameters, known as wing loading and thrust to weight ratio can be calculated. In this work, conceptual design procedure given by D. P. Raymer (AIAA Educational Series) is applied to calculate wing loading and thrust to weight ratio. The calculated values are compared against the actual values of the SR-71 aircraft. Results indicates that the values are in agreement with the trend of developments in aviation.

Site-specific photoconjugation of antibodies using chemically synthesized IgG-binding domains.

PubMed

Perols, Anna; Karlström, Amelie Eriksson

2014-03-19

Site-specific labeling of antibodies can be performed using the immunoglobulin-binding Z domain, derived from staphylococcal protein A (SpA), which has a well-characterized binding site in the Fc region of antibodies. By introducing a photoactivable probe in the Z domain, a covalent bond can be formed between the Z domain and the antibody by irradiation with UV light. The aim of this study was to improve the conjugation yield for labeling of different subclasses of IgG having different sequence composition, using a photoactivated Z domain variant. Four different variants of the Z domain (Z5BPA, Z5BBA, Z32BPA, and Z32BBA) were synthesized to investigate the influence of the position of the photoactivable probe and the presence of a flexible linker between the probe and the protein. For two of the variants, the photoreactive benzophenone group was introduced as part of an amino acid side chain by incorporation of the unnatural amino acid benzoylphenylalanine (BPA) during peptide synthesis. For the other two variants, the photoreactive benzophenone group was attached via a flexible linker by coupling of benzoylbenzoic acid (BBA) to the ε-amino group of a selectively deprotected lysine residue. Photoconjugation experiments using human IgG1, mouse IgG1, and mouse IgG2A demonstrated efficient conjugation for all antibodies. It was shown that differences in linker length had a large impact on the conjugation efficiency for labeling of mouse IgG1, whereas the positioning of the photoactivable probe in the sequence of the protein had a larger effect for mouse IgG2A. Conjugation to human IgG1 was only to a minor extent affected by position or linker length. For each subclass of antibody, the best variant tested using a standard conjugation protocol resulted in conjugation efficiencies of 41-66%, which corresponds to on average approximately one Z domain attached to each antibody. As a combination of the two best performing variants, Z5BBA and Z32BPA, a Z domain variant with two photoactivable probes (Z5BBA32BPA) was also synthesized with the aim of targeting a wider panel of antibody subclasses and species. This new reagent could efficiently couple to all antibody subclasses that were targeted by the single benzophenone-labeled Z domain variants, with conjugation efficiencies of 26-41%.

Precision medicine in allergic disease-food allergy, drug allergy, and anaphylaxis-PRACTALL document of the European Academy of Allergy and Clinical Immunology and the American Academy of Allergy, Asthma and Immunology.

PubMed

Muraro, A; Lemanske, R F; Castells, M; Torres, M J; Khan, D; Simon, H-U; Bindslev-Jensen, C; Burks, W; Poulsen, L K; Sampson, H A; Worm, M; Nadeau, K C

2017-07-01

This consensus document summarizes the current knowledge on the potential for precision medicine in food allergy, drug allergy, and anaphylaxis under the auspices of the PRACTALL collaboration platform. PRACTALL is a joint effort of the European Academy of Allergy and Clinical Immunology and the American Academy of Allergy, Asthma and Immunology, which aims to synchronize the European and American approaches to allergy care. Precision medicine is an emerging approach for disease treatment based on disease endotypes, which are phenotypic subclasses associated with specific mechanisms underlying the disease. Although significant progress has been made in defining endotypes for asthma, definitions of endotypes for food and drug allergy or for anaphylaxis lag behind. Progress has been made in discovery of biomarkers to guide a precision medicine approach to treatment of food and drug allergy, but further validation and quantification of these biomarkers are needed to allow their translation into practice in the clinical management of allergic disease. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Is Mitochondrial Donation Germ-Line Gene Therapy? Classifications and Ethical Implications.

PubMed

Newson, Ainsley J; Wrigley, Anthony

2017-01-01

The classification of techniques used in mitochondrial donation, including their role as purported germ-line gene therapies, is far from clear. These techniques exhibit characteristics typical of a variety of classifications that have been used in both scientific and bioethics scholarship. This raises two connected questions, which we address in this paper: (i) how should we classify mitochondrial donation techniques?; and (ii) what ethical implications surround such a classification? First, we outline how methods of genetic intervention, such as germ-line gene therapy, are typically defined or classified. We then consider whether techniques of mitochondrial donation fit into these, whether they might do so with some refinement of these categories, or whether they require some other approach to classification. To answer the second question, we discuss the relationship between classification and several key ethical issues arising from mitochondrial donation. We conclude that the properties characteristic of mitochondrial inheritance mean that most mitochondrial donation techniques belong to a new sub-class of genetic modification, which we call 'conditionally inheritable genomic modification' (CIGM). © 2017 John Wiley & Sons Ltd.

Implementation of a frame-based representation in CLIPS

NASA Technical Reports Server (NTRS)

Assal, Hisham; Myers, Leonard

1990-01-01

Knowledge representation is one of the major concerns in expert systems. The representation of domain-specific knowledge should agree with the nature of the domain entities and their use in the real world. For example, architectural applications deal with objects and entities such as spaces, walls, and windows. A natural way of representing these architectural entities is provided by frames. This research explores the potential of using the expert system shell CLIPS, developed by NASA, to implement a frame-based representation that can accommodate architectural knowledge. These frames are similar but quite different from the 'template' construct in version 4.3 of CLIPS. Templates support only the grouping of related information and the assignment of default values to template fields. In addition to these features frames provide other capabilities including definition of classes, inheritance between classes and subclasses, relation of objects of different classes with 'has-a', association of methods (demons) of different types (standard and user-defined) to fields (slots), and creation of new fields at run-time. This frame-based representation is implemented completely in CLIPS. No change to the source code is necessary.

Coordinated temporal and spatial control of motor neuron and serotonergic neuron generation from a common pool of CNS progenitors

PubMed Central

Pattyn, Alexandre; Vallstedt, Anna; Dias, José M.; Samad, Omar Abdel; Krumlauf, Robb; Rijli, Filippo M.; Brunet, Jean-Francois; Ericson, Johan

2003-01-01

Neural progenitor cells often produce distinct types of neurons in a specific order, but the determinants that control the sequential generation of distinct neuronal subclasses in the vertebrate CNS remain poorly defined. We examined the sequential generation of visceral motor neurons and serotonergic neurons from a common pool of neural progenitors located in the ventral hindbrain. We found that the temporal specification of these neurons varies along the anterior-posterior axis of the hindbrain, and that the timing of their generation critically depends on the integrated activities of Nkx- and Hox-class homeodomain proteins. A primary function of these proteins is to coordinate the spatial and temporal activation of the homeodomain protein Phox2b, which in turn acts as a binary switch in the selection of motor neuron or serotonergic neuronal fate. These findings assign new roles for Nkx, Hox, and Phox2 proteins in the control of temporal neuronal fate determination, and link spatial and temporal patterning of CNS neuronal fates. PMID:12651891

Forensic analysis of anthraquinone, azo, and metal complex acid dyes from nylon fibers by micro-extraction and capillary electrophoresis.

PubMed

Stefan, Amy R; Dockery, Christopher R; Nieuwland, Alexander A; Roberson, Samantha N; Baguley, Brittany M; Hendrix, James E; Morgan, Stephen L

2009-08-01

The extraction and separation of dyes present on textile fibers offers the possibility of enhanced discrimination between forensic trace fiber evidence. An automated liquid sample handling workstation was programmed to deliver varying solvent combinations to acid-dyed nylon samples, and the resulting extracts were analyzed by an ultraviolet/visible microplate reader to evaluate extraction efficiencies at different experimental conditions. Combinatorial experiments using three-component mixture designs varied three solvents (water, pyridine, and aqueous ammonia) and were employed at different extraction temperatures for various extraction durations. The extraction efficiency as a function of the three solvents (pyridine/ammonia/water) was modeled and used to define optimum conditions for the extraction of three subclasses of acid dyes (anthraquinone, azo, and metal complex) from nylon fibers. The capillary electrophoresis analysis of acid dye extracts is demonstrated using an electrolyte solution of 15 mM ammonium acetate in acetonitrile/water (40:60, v/v) at pH 9.3. Excellent separations and discriminating diode array spectra are obtained even for dyes of similar color.

Naturally Occurring Structural Isomers in Serum IgA1 O-Glycosylation

PubMed Central

Takahashi, Kazuo; Smith, Archer D.; Poulsen, Knud; Kilian, Mogens; Julian, Bruce A.; Mestecky, Jiri; Novak, Jan; Renfrow, Matthew B.

2013-01-01

IgA is the most abundantly produced antibody and plays an important role in the mucosal immune system. Human IgA is represented by two isotypes, IgA1 and IgA2. The major structural difference between these two subclasses is the presence of nine potential sites of O-glycosylation in the hinge region between the first and second constant region domains of the heavy chain. Thr225, Thr228, Ser230, Ser232 and Thr236 have been identified as the predominant sites of O-glycan attachment. The range and distribution of O-glycan chains at each site within the context of adjacent sites in this clustered region create a complex heterogeneity of surface epitopes that is incompletely defined. We previously described the analysis of IgA1 O-glycan heterogeneity by use of high resolution LC/MS and electron capture dissociation tandem MS to unambiguously localize all amino acid attachment sites in IgA1 (Ale) myeloma protein. Here, we report the identification and elucidation of IgA1 O-glycopeptide structural isomers that occur based on amino acid position of the attached glycans (positional isomers) and the structure of the O-glycan chains at individual sites (glycan isomers). These isomers are present in a model IgA1 (Mce1) myeloma protein and occur naturally in normal human serum IgA1. Variable O-glycan chains attached to Ser230, Thr233 or Thr236 produce the predominant positional isomers, including O-glycans composed of a single GalNAc residue. These findings represent the first definitive identification of structural isomeric IgA1 O-glycoforms, define the single-site heterogeneity for all O-glycan sites in a single sample, and have implications for defining epitopes based on clustered O-glycan variability. PMID:22067045

Structural Basis for FcγRIIa Recognition of Human IgG and Formation of Inflammatory Signaling Complexes

PubMed Central

Ramsland, Paul A.; Farrugia, William; Bradford, Tessa M.; Tan Sardjono, Caroline; Esparon, Sandra; Trist, Halina M.; Powell, Maree S.; Szee Tan, Peck; Cendron, Angela C.; Wines, Bruce D.; Scott, Andrew M.; Hogarth, P. Mark

2012-01-01

The interaction of Abs with their specific FcRs is of primary importance in host immune effector systems involved in infection and inflammation, and are the target for immune evasion by pathogens. FcγRIIa is a unique and the most widespread activating FcR in humans that through avid binding of immune complexes potently triggers inflammation. Polymorphisms of FcγRIIa (high responder/low responder [HR/LR]) are linked to susceptibility to infections, autoimmune diseases, and the efficacy of therapeutic Abs. In this article, we define the three-dimensional structure of the complex between the HR (arginine, R134) allele of FcγRIIa (FcγRIIa-HR) and the Fc region of a humanized IgG1 Ab, hu3S193. The structure suggests how the HR/LR polymorphism may influence FcγRIIa interactions with different IgG subclasses and glycoforms. In addition, mutagenesis defined the basis of the epitopes detected by FcR blocking mAbs specific for FcγRIIa (IV.3), FcγRIIb (X63-21), and a pan FcγRII Ab (8.7). The epitopes detected by these Abs are distinct, but all overlap with residues defined by crystallography to contact IgG. Finally, crystal structures of LR (histidine, H134) allele of FcγRIIa and FcγRIIa-HR reveal two distinct receptor dimers that may represent quaternary states on the cell surface. A model is presented whereby a dimer of FcγRIIa-HR binds Ag–Ab complexes in an arrangement that possibly occurs on the cell membrane as part of a larger signaling assembly. PMID:21856937

Semantique et psychologie (Semantics and Psychology)

ERIC Educational Resources Information Center

Le Ny, Jean-Francois

1975-01-01

Semantic activities constitute a sub-class of psychological activities; from this point of departure the article discusses such topics as: idiosyncrasies, meaning and causality, internal determinants, neo-associationism, componential theories, noun- and verb-formation, sentences and propositions, semantics and cognition, mnemesic compontents, and…

Dietary flavonoid intake at midlife and healthy aging in women.

PubMed

Samieri, Cécilia; Sun, Qi; Townsend, Mary K; Rimm, Eric B; Grodstein, Francine

2014-12-01

Dietary flavonoids have been related to lower risks of various chronic diseases, but it is unclear whether flavonoid intake in midlife helps to maintain good health and wellbeing in aging. We examined the relation of flavonoid intake in midlife with the prevalence of healthy aging. We included 13,818 women from the Nurses' Health Study with dietary data and no major chronic diseases in 1984-1986 when they were aged in their late 50s (median age: 59 y); all women provided information on multiple aspects of aging an average of 15 y later. Intakes of 6 major flavonoid subclasses in midlife were ascertained on the basis of averaged intakes of flavonoid-rich foods from 2 food-frequency questionnaires (1984-1986). We defined healthy compared with usual aging as of age 70 y; healthy aging was based on survival to ≥70 y with maintenance of 4 health domains (no major chronic diseases or major impairments in cognitive or physical function or mental health). Of women who survived until ≥70 y of age, 1517 women (11.0%) met our criteria for healthy aging. Compared with women in the lowest quintile of intake, women in the highest quintile of intake of several flavonoid subclasses at midlife had greater odds of healthy aging. After multivariable adjustment, ORs were as follows: flavones, 1.32 (95% CI: 1.10, 1.58); flavanone, 1.28 (95% CI: 1.08, 1.53); anthocyanin, 1.25 (95% CI: 1.04, 1.50); and flavonol, 1.18 (95% CI: 0.98, 1.42) (all P-trend ≤ 0.02). Consistently, greater intakes of major sources of these flavonoids (i.e., oranges, berries, onions, and apples) were associated with increased odds of healthy aging. We showed no association with flavan-3-ol monomers (P-trend = 0.80) or polymers (P-trend = 0.63). Higher intake of flavonoids at midlife, specifically flavones, flavanones, anthocyanins, and flavonols, is associated with greater likelihood of health and wellbeing in individuals surviving to older ages. © 2014 American Society for Nutrition.

Dietary flavonoid intake and risk of incident depression in midlife and older women123

PubMed Central

Rimm, Eric B; O’Reilly, Eilis J; Okereke, Olivia I

2016-01-01

Background: The impact of dietary flavonoid intakes on risk of depression is unclear. Objective: We prospectively examined associations between estimated habitual intakes of dietary flavonoids and depression risk. Design: We followed 82,643 women without a previous history of depression at baseline from the Nurses’ Health Study [(NHS) aged 53–80 y] and the Nurses’ Health Study II [(NHSII) aged 36–55 y]. Intakes of total flavonoids and subclasses (flavonols, flavones, flavanones, anthocyanins, flavan-3-ols, polymeric flavonoids, and proanthocyanidins) were calculated from validated food-frequency questionnaires collected every 2–4 y. Depression was defined as physician- or clinician-diagnosed depression or antidepressant use and was self-reported in response to periodic questionnaires. Cox proportional hazards models were performed to examine associations. Results: A total of 10,752 incident depression cases occurred during a 10-y follow-up. Inverse associations between flavonol, flavone, and flavanone intakes and depression risk were observed. Pooled multivariable-adjusted HRs (95% CIs) were 0.93 (0.88, 0.99), 0.92 (0.86, 0.98), and 0.90 (0.85, 0.96) when comparing the highest (quintile 5) with the lowest (quintile 1) quintiles, respectively, with evidence of linear trends across quintiles (P-trend = 0.0004–0.08). In flavonoid-rich food-based analyses, the HR was 0.82 (95% CI: 0.74, 0.91) among participants who consumed ≥2 servings citrus fruit or juices/d compared with <1 serving/wk. In the NHS only, total flavonoids, polymers, and proanthocyanidin intakes showed significantly (9–12%) lower depression risks. In analyses among late-life NHS participants (aged ≥65 y at baseline or during follow-up), for whom we were able to incorporate depressive symptoms into the outcome definition, higher intakes of all flavonoid subclasses except for flavan-3-ols were associated with significantly lower depression risk; flavones and proanthocyanidins showed the strongest associations (HR for both: 0.83; 95% CI: 0.77, 0.90). Conclusions: Higher flavonoid intakes may be associated with lower depression risk, particularly among older women. Further studies are needed to confirm these associations. PMID:27413131

Dietary flavonoid intake and risk of incident depression in midlife and older women.

PubMed

Chang, Shun-Chiao; Cassidy, Aedin; Willett, Walter C; Rimm, Eric B; O'Reilly, Eilis J; Okereke, Olivia I

2016-09-01

The impact of dietary flavonoid intakes on risk of depression is unclear. We prospectively examined associations between estimated habitual intakes of dietary flavonoids and depression risk. We followed 82,643 women without a previous history of depression at baseline from the Nurses' Health Study [(NHS) aged 53-80 y] and the Nurses' Health Study II [(NHSII) aged 36-55 y]. Intakes of total flavonoids and subclasses (flavonols, flavones, flavanones, anthocyanins, flavan-3-ols, polymeric flavonoids, and proanthocyanidins) were calculated from validated food-frequency questionnaires collected every 2-4 y. Depression was defined as physician- or clinician-diagnosed depression or antidepressant use and was self-reported in response to periodic questionnaires. Cox proportional hazards models were performed to examine associations. A total of 10,752 incident depression cases occurred during a 10-y follow-up. Inverse associations between flavonol, flavone, and flavanone intakes and depression risk were observed. Pooled multivariable-adjusted HRs (95% CIs) were 0.93 (0.88, 0.99), 0.92 (0.86, 0.98), and 0.90 (0.85, 0.96) when comparing the highest (quintile 5) with the lowest (quintile 1) quintiles, respectively, with evidence of linear trends across quintiles (P-trend = 0.0004-0.08). In flavonoid-rich food-based analyses, the HR was 0.82 (95% CI: 0.74, 0.91) among participants who consumed ≥2 servings citrus fruit or juices/d compared with <1 serving/wk. In the NHS only, total flavonoids, polymers, and proanthocyanidin intakes showed significantly (9-12%) lower depression risks. In analyses among late-life NHS participants (aged ≥65 y at baseline or during follow-up), for whom we were able to incorporate depressive symptoms into the outcome definition, higher intakes of all flavonoid subclasses except for flavan-3-ols were associated with significantly lower depression risk; flavones and proanthocyanidins showed the strongest associations (HR for both: 0.83; 95% CI: 0.77, 0.90). Higher flavonoid intakes may be associated with lower depression risk, particularly among older women. Further studies are needed to confirm these associations.

Features versus context: An approach for precise and detailed detection and delineation of faces and facial features.

PubMed

Ding, Liya; Martinez, Aleix M

2010-11-01

The appearance-based approach to face detection has seen great advances in the last several years. In this approach, we learn the image statistics describing the texture pattern (appearance) of the object class we want to detect, e.g., the face. However, this approach has had limited success in providing an accurate and detailed description of the internal facial features, i.e., eyes, brows, nose, and mouth. In general, this is due to the limited information carried by the learned statistical model. While the face template is relatively rich in texture, facial features (e.g., eyes, nose, and mouth) do not carry enough discriminative information to tell them apart from all possible background images. We resolve this problem by adding the context information of each facial feature in the design of the statistical model. In the proposed approach, the context information defines the image statistics most correlated with the surroundings of each facial component. This means that when we search for a face or facial feature, we look for those locations which most resemble the feature yet are most dissimilar to its context. This dissimilarity with the context features forces the detector to gravitate toward an accurate estimate of the position of the facial feature. Learning to discriminate between feature and context templates is difficult, however, because the context and the texture of the facial features vary widely under changing expression, pose, and illumination, and may even resemble one another. We address this problem with the use of subclass divisions. We derive two algorithms to automatically divide the training samples of each facial feature into a set of subclasses, each representing a distinct construction of the same facial component (e.g., closed versus open eyes) or its context (e.g., different hairstyles). The first algorithm is based on a discriminant analysis formulation. The second algorithm is an extension of the AdaBoost approach. We provide extensive experimental results using still images and video sequences for a total of 3,930 images. We show that the results are almost as good as those obtained with manual detection.

Prairie basin wetlands of the Dakotas: a community profile

USGS Publications Warehouse

Kantrud, H.A.; Krapu, G.L.; Swanson, G.A.

1989-01-01

This description of prairie basin wetlands of the Dakotas is part of a series of community profiles on ecologically important wetlands of national significance. The shallow wetlands of the Dakotas form the bulk of the portion of the Prairie Pothole Region lying within the United States. This region is famous as the producer of at least half of North America's waterfowl and an unknown, but large, proportion of other prairie-dwelling marsh and aquatic birds.The wetlands described here lie in relatively small, shallow basins that vary greatly in their ability to maintain surface water, and in their water chemistry, which varies from fresh to hypersaline. These wetlands occur in a wide variety of hydrological settings, in an area where annual and seasonal precipitation varies greatly in form and amount. Thus the presence of surface water in these wetlands is largely unpredictable. Superimposed on these phenomena are the effects of a variety of land uses, including pasture, cultivation, mechanical forage removal, idle conditions and burning. All those factors greatly affect the plant and animal communities found in these basins.This profile covers lacustrine and palustrine basins with temporarily flooded, seasonally flooded, and semipermanently flooded water regimes. Basins with these water regimes compose about 90% of the basins in the Prairie Pothole Region of the Dakotas. This profile outlines the wetland subsystems, classes and subclasses that occur in these basins, and provides a useful reference to their geologic, climatic, hydrologic, and pedologic setting.Detailed information on the biotic environment of the wetlands dealt with in this profile will be useful to scientists and resource managers. Special recognition is paid to the macrophyte and invertebrate communities, which have dynamic qualities found in few other of the world's wetland ecosystems.The most noteworthy animal inhabitants of these basins are waterfowl, which are a resource of international concern. Because of the importance of this resource, much research on the habitat use and feeding ecology of breeding waterfowl has been conducted in the region. These topics receive special attention in this profile.The Prairie Pothole Region is a major world supplier of cereal grains. Consequently, wetlands in the region are often drained for crop production or otherwise cropped when water conditions permit. These practices degrade the value of wetlands for most species of wildlife and conflict with the aims of conservationists. The subject of human uses and impacts to prairie wetlands is thus an important part of this profile.

An iterative approach to optimize change classification in SAR time series data

NASA Astrophysics Data System (ADS)

Boldt, Markus; Thiele, Antje; Schulz, Karsten; Hinz, Stefan

2016-10-01

The detection of changes using remote sensing imagery has become a broad field of research with many approaches for many different applications. Besides the simple detection of changes between at least two images acquired at different times, analyses which aim on the change type or category are at least equally important. In this study, an approach for a semi-automatic classification of change segments is presented. A sparse dataset is considered to ensure the fast and simple applicability for practical issues. The dataset is given by 15 high resolution (HR) TerraSAR-X (TSX) amplitude images acquired over a time period of one year (11/2013 to 11/2014). The scenery contains the airport of Stuttgart (GER) and its surroundings, including urban, rural, and suburban areas. Time series imagery offers the advantage of analyzing the change frequency of selected areas. In this study, the focus is set on the analysis of small-sized high frequently changing regions like parking areas, construction sites and collecting points consisting of high activity (HA) change objects. For each HA change object, suitable features are extracted and a k-means clustering is applied as the categorization step. Resulting clusters are finally compared to a previously introduced knowledge-based class catalogue, which is modified until an optimal class description results. In other words, the subjective understanding of the scenery semantics is optimized by the data given reality. Doing so, an even sparsely dataset containing only amplitude imagery can be evaluated without requiring comprehensive training datasets. Falsely defined classes might be rejected. Furthermore, classes which were defined too coarsely might be divided into sub-classes. Consequently, classes which were initially defined too narrowly might be merged. An optimal classification results when the combination of previously defined key indicators (e.g., number of clusters per class) reaches an optimum.

The Profile-Query Relationship.

ERIC Educational Resources Information Center

Shepherd, Michael A.; Phillips, W. J.

1986-01-01

Defines relationship between user profile and user query in terms of relationship between clusters of documents retrieved by each, and explores the expression of cluster similarity and cluster overlap as linear functions of similarity existing between original pairs of profiles and queries, given the desired retrieval threshold. (23 references)…

IgG subclass antibodies to human and bacterial HSP60 are not associated with disease activity and progression over time in axial spondyloarthritis

PubMed Central

2013-01-01

Introduction Spondyloarthritis (SpA), an interrelated group of rheumatic diseases, has been suggested to be triggered by bacterial infections prior to the development of an autoimmune response that causes inflammation of the spinal and peripheral joints. Because human heat shock protein 60 (HSP60), recently renamed HSPD1, and bacterial HSP60 are highly homologous, immunological cross-reactivity has been proposed as a mechanism of disease initiation. However, previous investigations of the humoral immune response to HSP60 in SpA patients have lacked determination of immunoglobulin G (IgG) subclasses and patient follow-up. In this study, we have focused on these parameters in a cohort of axial SpA patients with a well-established set of clinical characteristics, including MRI changes and human leukocyte antigen B27. Methods IgG subclass antibodies (IgG1, IgG2, IgG3 and IgG4) against recombinant HSP60 of three reactive arthritis-related bacteria; human HSP60; and the microorganisms Chlamydia trachomatis and C. pneumoniae were determined by ELISA. Serum samples collected from 2004 to 2006 and in 2010 and 2011 from 39 axial SpA patients were analyzed and compared with samples from 39 healthy controls. The Mann-Whitney U test and Wilcoxon matched pairs test were used to compare the antibody levels in different and paired groups, respectively. P < 0.01 was considered significant. The Spearman nonparametric correlation was used to determine correlation between antibody levels and between antibody levels and the disease parameters. Results Elevated levels of IgG1 and IgG3 to human HSP60 and IgG1 to HSP60 of Salmonella enterica Enteritidis were observed in SpA patients compared with healthy controls at both time points. The antibody levels were almost constant over time for IgG1, whereas high levels of IgG3 to human HSP60 tended to decrease over time. The antibody response to human HSP60 was predominantly of the IgG3 subclass, and patients with high levels of IgG3 to this antigen had low levels of IgG1, indicating an inverse association. Different IgG subclasses were produced against bacterial and human HSP60 in the same serum sample, IgG1 and IgG3, respectively, indicating that there was no cross-reaction. Conclusions A significant association was observed between axial SpA and the presence of IgG1/IgG3 antibodies to human HSP60 and of IgG1 to S. enterica Enteritidis and C. trachomatis. Generation of antibodies to human HSP60 was independent of the presence of antibodies to bacterial HSP60. No association was observed between clinical and MRI changes with antibodies over time. Altogether, such antibodies do not reflect the disease activity in these patients. This study has been approved by the Regional Research Ethics Committee of Central Jutland, Denmark. Trial registration numbers: 20050046 and 20100083 PMID:23705835

37 CFR 1.76 - Application data sheet.

Code of Federal Regulations, 2011 CFR

2011-07-01

... Section 1.76 Patents, Trademarks, and Copyrights UNITED STATES PATENT AND TRADEMARK OFFICE, DEPARTMENT OF... title of the invention, a suggested classification, by class and subclass, the Technology Center to... and Technology Center information should be supplied for provisional applications whether or not...

Development of USDA's expanded flavonoid database: A Tool for Epidemiological Research

USDA-ARS?s Scientific Manuscript database

The scientific community continues to be interested in potential links between flavonoid intakes and beneficial health effects associated with certain chronic diseases such as cardiovascular diseases, some cancers and type 2 diabetes. Three separate flavonoid databases (Flavonoids (5 subclasses: fl...

Distribution of C22-, C24- and C26-alpha-unit-containing mycolic acid homologues in mycobacteria.

PubMed

Kaneda, K; Imaizumi, S; Yano, I

1995-01-01

There are three mycolic acid homologues with C22-, C24- and C26-alpha-units in Mycobacterium. In order to reveal the composition and distribution of these homologues in each subclass and molecular species of mycolic acids and to compare them with the composition of constitutive non-polar fatty acids (free and bound forms), we have separated non-polar fatty acids and each subclass of mycolic acids from 21 mycobacterial species by thin-layer chromatography, and analyzed non-polar fatty acid methyl esters by gas chromatography (GC) and the cleavage products of methyl mycolate by pyrolysis GC. We further performed mass chromatographic analysis of trimethylsilyl (TMS) ether derivatives of mycolic acid methyl esters by monitoring [B-29]+ ions (loss of CHO from the alpha-branched-chain structure of mycolic acids) of m/z 426, 454 and 482 which are attributed to C22-, C24- and C26-alpha-units of TMS ether derivatives of methyl mycolates, respectively, (Kaneda, K. et al, J. Clin. Microbiol. 24: 1060-1070, 1986). By pyrolysis GC, C22:0, C24:0 and C26:0 fatty acid methyl esters generated by the C2-C3 cleavage of C22-, C24- and C26-alpha-unit-containing mycolic acid methyl esters, respectively, were detected. Their proportion was almost the same among subclasses of mycolic acids in every Mycobacterium and also similar to the proportion of constitutive non-polar C22:0, C24:0 and C26:0 fatty acids. By mass chromatography, the composition and distribution of C22- and C24-alpha-unit-containing homologues were revealed to be similar between alpha- and alpha'-mycolic acids in every Mycobacterium.(ABSTRACT TRUNCATED AT 250 WORDS)

Human IgG2- and IgG4-expressing memory B cells display enhanced molecular and phenotypic signs of maturity and accumulate with age.

PubMed

de Jong, Britt G; IJspeert, Hanna; Marques, Lemelinda; van der Burg, Mirjam; van Dongen, Jacques Jm; Loos, Bruno G; van Zelm, Menno C

2017-10-01

The mechanisms involved in sequential immunoglobulin G (IgG) class switching are still largely unknown. Sequential IG class switching is linked to higher levels of somatic hypermutation (SHM) in vivo, but it remains unclear if these are generated temporally during an immune response or upon activation in a secondary response. We here aimed to uncouple these processes and to distinguish memory B cells from primary and secondary immune responses. SHM levels and IgG subclasses were studied with 454 pyrosequencing on blood mononuclear cells from young children and adults as models for primary and secondary immunological memory. Additional sequencing and detailed immunophenotyping with IgG subclass-specific antibodies was performed on purified IgG + memory B-cell subsets. In both children and adults, SHM levels were higher in transcripts involving more downstream-located IGHG genes (esp. IGHG2 and IGHG4). In adults, SHM levels were significantly higher than in children, and downstream IGHG genes were more frequently utilized. This was associated with increased frequencies of CD27 + IgG + memory B cells, which contained higher levels of SHM, more IGHG2 usage, and higher expression levels of activation markers than CD27 - IgG + memory B cells. We conclude that secondary immunological memory accumulates with age and these memory B cells express CD27, high levels of activation markers, and carry high SHM levels and frequent usage of IGHG2. These new insights contribute to our understanding of sequential IgG subclass switching and show a potential relevance of using serum IgG2 levels or numbers of IgG2-expressing B cells as markers for efficient generation of memory responses.

HDL2-cholesterol/HDL3-cholesterol ratio was associated with insulin resistance, high-molecular-weight adiponectin, and components for metabolic syndrome in Japanese.

PubMed

Moriyama, Kengo; Negami, Masako; Takahashi, Eiko

2014-11-01

Recent data have suggested a relationship between the high-density lipoprotein (HDL) subclass ratio and metabolic syndrome (MetS). However, limited information is available regarding the relationships between the HDL subclass ratio and insulin resistance, associated adipocytokine levels, and MetS components. The associations of the high-density lipoprotein 2 cholesterol (HDL2-C) to high-density lipoprotein 3 cholesterol (HDL3-C) ratio with the homeostasis model assessment of insulin resistance (HOMA-IR) index, high-molecular-weight adiponectin (HMW-Ad) levels, and MetS components were examined. The study included 1155 Japanese subjects who met our inclusion criteria and underwent an annual health examination that included an HDL subclass analysis. The HDL2-C/HDL3-C ratio and the HMW-Ad level gradually decreased as the number of MetS components increased. In contrast, HOMA-IR gradually increased as the number of MetS components increased. The HDL2-C/HDL3-C ratio correlated inversely with HOMA-IR and positively with the HMW-Ad level. A strong positive correlation was observed between the HDL2-C/HDL3-C ratio and the HDL-C level. The HDL2-C/HDL3-C ratio exhibited moderate negative correlations with the body mass index, waist circumference, and triglyceride level. Weak negative correlations were observed for the HDL2-C/HDL3-C ratio with the systolic and diastolic blood pressure and fasting plasma glucose levels. Our data indicated that the HDL2-C/HDL3-C ratio was associated with insulin resistance, the HMW-Ad level, and MetS components, and it was useful for evaluating MetS in Japanese individuals. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

COMMON PATTERNS IN THE EVOLUTION BETWEEN THE LUMINOUS NEUTRON STAR LOW-MASS X-RAY BINARY SUBCLASSES

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fridriksson, Joel K.; Homan, Jeroen; Remillard, Ronald A., E-mail: J.K.Fridriksson@uva.nl

2015-08-10

The X-ray transient XTE J1701–462 was the first source observed to evolve through all known subclasses of low-magnetic-field neutron star low-mass X-ray binaries (NS-LMXBs), as a result of large changes in its mass accretion rate. To investigate to what extent similar evolution is seen in other NS-LMXBs we have performed a detailed study of the color–color and hardness–intensity diagrams (CDs and HIDs) of Cyg X-2, Cir X-1, and GX 13+1—three luminous X-ray binaries, containing weakly magnetized neutron stars, known to exhibit strong secular changes in their CD/HID tracks. Using the full set of Rossi X-ray Timing Explorer Proportional Counter Arraymore » data collected for the sources over the 16 year duration of the mission, we show that Cyg X-2 and Cir X-1 display CD/HID evolution with close similarities to XTE J1701–462. Although GX 13+1 shows behavior that is in some ways unique, it also exhibits similarities to XTE J1701–462, and we conclude that its overall CD/HID properties strongly indicate that it should be classified as a Z source, rather than as an atoll source. We conjecture that the secular evolution of Cyg X-2, Cir X-1, and GX 13+1—illustrated by sequences of CD/HID tracks we construct—arises from changes in the mass accretion rate. Our results strengthen previous suggestions that within single sources Cyg-like Z source behavior takes place at higher luminosities and mass accretion rates than Sco-like Z behavior, and lend support to the notion that the mass accretion rate is the primary physical parameter distinguishing the various NS-LMXB subclasses.« less

Distinct Immunoglobulin Class and Immunoglobulin G Subclass Patterns against Ganglioside GQ1b in Miller Fisher Syndrome following Different Types of Infection

PubMed Central

Schwerer, Beatrix; Neisser, Andrea; Bernheimer, Hanno

1999-01-01

We studied serum antibodies against gangliosides GQ1b and GM1 in 13 patients with Miller Fisher syndrome (MFS) and in 18 patients with Guillain-Barré syndrome (GBS) with cranial nerve involvement. Anti-GQ1b titers were elevated in all patients with MFS cases (immunoglobulin G [IgG] > IgA, IgM), and in 8 of the 18 with GBS. Lower frequencies of increased anti-GM1 titers were observed in MFS patients (3 of 13), as well as in GBS patients (5 of 18). During the course of MFS, anti-GQ1b titers of all Ig classes decreased within 3 weeks after onset. By contrast, anti-GM1 titers (mainly IgM) transiently increased during the course of MFS in five of six patients, suggesting a nonspecific secondary immune response. In patients with MFS following respiratory infections, IgG was the major anti-GQ1b Ig class (six of six patients) and IgG3 was the major subclass (five of six). In contrast, four of five patients with MFS following gastrointestinal infections showed predominance of anti-GQ1b IgA or IgM over IgG and predominance of the IgG2 subclass; anti-GQ1b IgG (IgG3) prevailed in one patient only. These distinct Ig patterns strongly suggest that different infections may trigger different mechanisms of anti-GQ1b production, such as via T-cell-dependent as opposed to T-cell-independent pathways. Thus, the origin of antibodies against GQ1b in MFS may be determined by the type of infectious agent that precipitates the disease. PMID:10225903

Can non-cholesterol sterols and lipoprotein subclasses distribution predict different patterns of cholesterol metabolism and statin therapy response?

PubMed

Gojkovic, Tamara; Vladimirov, Sandra; Spasojevic-Kalimanovska, Vesna; Zeljkovic, Aleksandra; Vekic, Jelena; Kalimanovska-Ostric, Dimitra; Djuricic, Ivana; Sobajic, Sladjana; Jelic-Ivanovic, Zorana

2017-03-01

Cholesterol homeostasis disorders may cause dyslipidemia, atherosclerosis progression and coronary artery disease (CAD) development. Evaluation of non-cholesterol sterols (NCSs) as synthesis and absorption markers, and lipoprotein particles quality may indicate the dyslipidemia early development. This study investigates associations of different cholesterol homeostasis patterns with low-density (LDL) and high-density lipoproteins (HDL) subclasses distribution in statin-treated and statin-untreated CAD patients, and potential use of aforementioned markers for CAD treatment optimization. The study included 78 CAD patients (47 statin-untreated and 31 statin-treated) and 31 controls (CG). NCSs concentrations were quantified using gas chromatography- flame ionization detection (GC-FID). Lipoprotein subclasses were separated by gradient gel electrophoresis. In patients, cholesterol-synthesis markers were significantly higher comparing to CG. Cholesterol-synthesis markers were inversely associated with LDL size in all groups. For cholesterol homeostasis estimation, each group was divided to good and/or poor synthetizers and/or absorbers according to desmosterol and β-sitosterol median values. In CG, participants with reduced cholesterol absorption, the relative proportion of small, dense LDL was higher in those with increased cholesterol synthesis compared to those with reduced synthesis (p<0.01). LDL I fraction was significantly higher in poor synthetizers/poor absorbers subgroup compared to poor synthetizers/good absorbers (p<0.01), and good synthetizers/poor absorbers (p<0.01). Statin-treated patients with increased cholesterol absorption had increased proportion of LDL IVB (p<0.05). The results suggest the existence of different lipoprotein abnormalities according to various patterns of cholesterol homeostasis. Desmosterol/β-sitosterol ratio could be used for estimating individual propensity toward dyslipidemia development and direct the future treatment.

Antibody repertoire development in fetal and neonatal piglets. XVII. IgG subclass transcription revisited with emphasis on new IgG3.

PubMed

Butler, John E; Wertz, Nancy

2006-10-15

Fetal piglets offer an in vivo model for determining whether Ag-independent IgG subclass transcription proceeds in a manner that differs from subclass transcription in pigs exposed to environmental Ags and TLR ligands. Our data from approximately 12,000 Cgamma clones from > 60 piglets provide the first report on the relative usage of all known porcine Cgamma genes in fetal and young pigs. Studies revealed that among the six Cgamma genes, allelic variants of IgG1 comprised 50-80% of the repertoire, and IgG2 alleles comprised < 10% in nearly all tissues. However, relative transcription of allelic variants of IgG1 randomly deviate from the 1:1 ratio expected in heterozygotes. Most surprising was the finding that IgG3 accounted for half of all Cgamma transcripts in the ileal Peyer's patches (IPPs) and mesenteric lymph nodes but on average only approximately 5% of the clones from the thymus, tonsil, spleen, peripheral blood, and bone marrow of newborns. Lymphoid tissues from late term fetuses revealed a similar expression pattern. Except for IgG3 in the IPPs and mesenteric lymph nodes, no stochastic pattern of Cgamma expression during development was seen in animals from mid-gestation through 5 mo. The age and tissue dependence of IgG3 transcription paralleled the developmental persistence of the IPP, and its near disappearance corresponds to the diversification of the preimmune VDJ repertoire in young piglets. We hypothesize that long-hinged porcine IgG3 may be important in preadaptive responses to T cell-independent Ags similar to those described for its murine namesake.

Bundling Post-Acute Care Services into MS-DRG Payments

PubMed Central

Vertrees, James C.; Averill, Richard F.; Eisenhandler, Jon; Quain, Anthony; Switalski, James

2013-01-01

Objective A bundled hospital payment system that encompasses both acute and post-acute care has been proposed as a means of creating financial incentives in the Medicare fee-for-service system to foster care coordination and to improve the current disorganized system of post care. The objective of this study was to evaluate the statistical stability of alternative designs of a hospital payment system that includes post-acute care services to determine the feasibility of using a combined hospital and post-acute care bundle as a unit of payment. Methods The Medicare Severity-Diagnosis Related Groups (MS-DRGs) were subdivided into clinical subclasses that measured a patient's chronic illness burden to test whether a patient's chronic illness burden had a substantial impact on post-acute care expenditures. Using Medicare data the statistical performance of the MS-DRGs with and without the chronic illness subclasses was evaluated across a wide range of post-acute care windows and combinations of post-acute care service bundles using both submitted charges and Medicare payments. Results The statistical performance of the MS-DRGs as measured by R2 was consistently better when the chronic illness subclasses are included indicating that MS-DRGs by themselves are an inadequate unit of payment for post-acute care payment bundles. In general, R2 values increased as the post-acute care window length increased and decreased as more services were added to the post-acute care bundle. Discussion The study results suggest that it is feasible to develop a payment system that incorporates significant post-acute care services into the MS-DRG inpatient payment bundle. This expansion of the basic DRG payment approach can provide a strong financial incentive for providers to better coordinate care potentially leading to improved efficiency and outcome quality. PMID:24753970

Flavonoids, flavonoid-rich foods, and cardiovascular risk: a meta-analysis of randomized controlled trials.

PubMed

Hooper, Lee; Kroon, Paul A; Rimm, Eric B; Cohn, Jeffrey S; Harvey, Ian; Le Cornu, Kathryn A; Ryder, Jonathan J; Hall, Wendy L; Cassidy, Aedín

2008-07-01

The beneficial effects of flavonoid consumption on cardiovascular risk are supported by mechanistic and epidemiologic evidence. We aimed to systematically review the effectiveness of different flavonoid subclasses and flavonoid-rich food sources on cardiovascular disease (CVD) and risk factors--ie, lipoproteins, blood pressure, and flow-mediated dilatation (FMD). Methods included a structured search strategy on MEDLINE, EMBASE, and Cochrane databases; formal inclusion or exclusion, data extraction, and validity assessment; and meta-analysis. One hundred thirty-three trials were included. No randomized controlled trial studied effects on CVD morbidity or mortality. Significant heterogeneity confirmed differential effects between flavonoid subclasses and foods. Chocolate increased FMD after acute (3.99%; 95% CI: 2.86, 5.12; 6 studies) and chronic (1.45%; 0.62, 2.28; 2 studies) intake and reduced systolic (-5.88 mm Hg; -9.55, -2.21; 5 studies) and diastolic (-3.30 mm Hg; -5.77, -0.83; 4 studies) blood pressure. Soy protein isolate (but not other soy products or components) significantly reduced diastolic blood pressure (-1.99 mm Hg; -2.86, -1.12; 9 studies) and LDL cholesterol (-0.19 mmol/L; -0.24, -0.14; 39 studies). Acute black tea consumption increased systolic (5.69 mm Hg; 1.52, 9.86; 4 studies) and diastolic (2.56 mm Hg; 1.03, 4.10; 4 studies) blood pressure. Green tea reduced LDL (-0.23 mmol/L; -0.34, -0.12; 4 studies). For many of the other flavonoids, there was insufficient evidence to draw conclusions about efficacy. To date, the effects of flavonoids from soy and cocoa have been the main focus of attention. Future studies should focus on other commonly consumed subclasses (eg, anthocyanins and flavanones), examine dose-response effects, and be of long enough duration to allow assessment of clinically relevant endpoints.

Measurement of the IgG2 response to Pneumococcal capsular polysaccharides may identify an antibody deficiency in individuals referred for immunological investigation.

PubMed

Parker, Antony; Irure Ventura, Juan; Sims, Dawn; Echeverría de Carlos, Ainara; Gómez de la Torre, Ricardo; Tricas Aizpún, Lourdes; Ocejo-Vinyals, J Gonzalo; López-Hoyos, Marcos; Wallis, Gregg; Harding, Stephen

2017-01-01

IgG2 is the most efficient subclass for providing protection against pneumococcal pathogens. We hypothesised that some individuals may be unable to mount an effective pneumococcal capsular polysaccharide (PCP) IgG2 response despite having a normal PCP IgG concentration (PCP IgG2 deficient). The median pre-vaccination PCP IgG2 concentration was significantly lower in individuals referred for immunological investigation compared to healthy controls (2.8 mg/L range, 95% CI 1.1-88 vs. 29.5mg/L, 95% CI 13.5-90, p = 0.0002). PCP IgG:IgG2 ratios were significantly higher for the referral population than for healthy controls suggesting the increased production of PCP specific subclasses other than IgG2. The percentage of individuals with PCP IgG2 deficiency was significantly higher in referral groups compared to controls (31% vs. 5%; p = 0.0009) and in an individual with PCP IgG2 deficiency, the balance of PCP specific IgG subclass antibodies post vaccination changed from IgG2>IgG1>IgG3>IgG4 to IgG1>IgG3>IgG2>IgG4. The median PCP IgG2 concentration in those with PCP IgG2 deficiency was significantly lower in the referral groups compared to controls (7.8 mg/L, 95% CI 1.1-12 vs. 12.7 mg/L, 95% CI 11.8-13.1; p = 0.006). The data suggests a defect in the production PCP IgG2 may be present in individuals with normal PCP IgG referred for immunological investigation.

Genetic and biochemical characterization of HMB-1, a novel subclass B1 metallo-β-lactamase found in a Pseudomonas aeruginosa clinical isolate.

PubMed

Pfennigwerth, Niels; Lange, Felix; Belmar Campos, Cristina; Hentschke, Moritz; Gatermann, Sören G; Kaase, Martin

2017-04-01

To characterize a novel subclass B1 metallo-β-lactamase (MBL) found in an MDR Pseudomonas aeruginosa clinical isolate. The isolate P. aeruginosa NRZ-03096 was recovered in 2012 from an anal swab from a patient hospitalized in Northern Germany and showed high MICs of carbapenems. MBL production was analysed by several phenotypic tests. Genetic characterization of the novel bla gene and MLST was performed by WGS. The novel bla gene was expressed in Escherichia coli TOP10 and the enzyme was subjected to biochemical characterization to determine the kinetic parameters K m and k cat . P. aeruginosa NRZ-03096 was resistant to all tested β-lactams and showed an MBL phenotype. Shotgun cloning experiments yielded a clone producing a novel subclass B1 enzyme with only 74.3% identity to the next nearest relative, KHM-1. The novel MBL was named HMB-1 (for Hamburg MBL). Analysis of WGS data showed that the bla HMB-1 gene was chromosomally located as part of a Tn 3 family transposon that was named Tn 6345 . Expression of bla HMB-1 in E. coli TOP10 led to increased resistance to β-lactams. Determination of K m and k cat revealed that HMB-1 had different hydrolytic characteristics compared with KHM-1, with lower hydrolytic rates for cephalosporins and a higher rate for imipenem. The identification of HMB-1 further underlines the ongoing spread and diversification of carbapenemases in Gram-negative human pathogens and especially in P. aeruginosa . © The Author 2017. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

The RINGO2 and DIPOL optical polarization catalogue of blazars

NASA Astrophysics Data System (ADS)

Jermak, H.; Steele, I. A.; Lindfors, E.; Hovatta, T.; Nilsson, K.; Lamb, G. P.; Mundell, C.; Barres de Almeida, U.; Berdyugin, A.; Kadenius, V.; Reinthal, R.; Takalo, L.

2016-11-01

We present ˜2000 polarimetric and ˜3000 photometric observations of 15 γ-ray bright blazars over a period of 936 days (2008-10-11 to 2012-10-26) using data from the Tuorla blazar monitoring program (KVA DIPOL) and Liverpool Telescope (LT) RINGO2 polarimeters (supplemented with data from SkyCamZ (LT) and Fermi-LAT γ-ray data). In 11 out of 15 sources we identify a total of 19 electric vector position angle (EVPA) rotations and 95 flaring episodes. We group the sources into subclasses based on their broad-band spectral characteristics and compare their observed optical and γ-ray properties. We find that (1) the optical magnitude and γ-ray flux are positively correlated, (2) EVPA rotations can occur in any blazar subclass, four sources show rotations that go in one direction and immediately rotate back, (3) we see no difference in the γ-ray flaring rates in the sample; flares can occur during and outside of rotations with no preference for this behaviour, (4) the average degree of polarization (DoP), optical magnitude and γ-ray flux are lower during an EVPA rotation compared with during non-rotation and the distribution of the DoP during EVPA rotations is not drawn from the same parent sample as the distribution outside rotations, (5) the number of observed flaring events and optical polarization rotations are correlated, however we find no strong evidence for a temporal association between individual flares and rotations and (6) the maximum observed DoP increases from ˜10 per cent to ˜30 per cent to ˜40 per cent for subclasses with synchrotron peaks at high, intermediate and low frequencies, respectively.

Student Competency Profile Chart: A Competency Based Vocational Education Instrument.

ERIC Educational Resources Information Center

Martell, John L.

This document defines, describes usage of, and provides samples of student competency profiles being used in 17 vocational programs at Rutland Area Vocational-Technical Center in Rutland, Vermont. The profiles cover the following programs: auto body, auto mechanics, business/data processing, cabinetmaking, carpentry/masonry, culinary arts,…

Hepatic metabolite profiles in mice with a suboptimal selenium status.

PubMed

Geillinger, Kerstin E; Rathmann, Daniel; Köhrle, Josef; Fiamoncini, Jarlei; Daniel, Hannelore; Kipp, Anna P

2014-09-01

Selenium is an essential trace element and mediates its functions via various selenoproteins such as glutathione peroxidases or thioredoxin reductases. A suboptimal selenium supply causes metabolic disturbances and is associated with an increased risk to develop different disorders, including cancer or cardiovascular diseases. This study aimed to assess the impact of a suboptimal selenium status on the hepatic metabolome of male mice analyzed by a targeted liquid chromatography/tandem mass spectrometry and a method based on non-targeted gas chromatography hyphenated with mass spectrometry. Feeding animals a diet with about half of the recommended selenium content supplied as selenomethionine caused liver glutathione peroxidase and thioredoxin reductase activities to decline and lipid peroxidation to increase. Serum T3 thyroid hormone concentration also declined via a reduced hepatic deiodinase activity. Metabolite profiling revealed predominantly changes in cysteine and carbon-1 metabolism as well as in selected lipid subclasses. In particular the concentrations of palmitoylcarnitines and oleoylcarnitines (C18:1 and C16:1) and various phosphatidylcholine species containing saturated fatty acids were elevated. Increased taurine levels suggested an enhanced cysteine flux through the salvage pathway whereas increased homocysteine levels appeared to be a consequence of a massive down-regulation of cystathionine β lyase (cystathionine β synthase) and a reduced flux through the transsulfuration pathway. The findings demonstrate that a suboptimal selenium status causes alterations in lipid and carbon-1 metabolism in mouse liver. These changes may contribute to the development of diseases associated with a suboptimal selenium status. Copyright © 2014 Elsevier Inc. All rights reserved.

Use of Length Heterogeneity PCR and Fatty Acid Methyl Ester Profiles To Characterize Microbial Communities in Soil†

PubMed Central

Ritchie, Nancy J.; Schutter, Mary E.; Dick, Richard P.; Myrold, David D.

2000-01-01

In length heterogeneity PCR (LH-PCR) a fluorescently labeled primer is used to determine the relative amounts of amplified sequences originating from different microorganisms. Labeled fragments are separated by gel electrophoresis and detected by laser-induced fluorescence with an automated gene sequencer. We used LH-PCR to evaluate the composition of the soil microbial community. Four soils, which differed in terms of soil type and/or crop management practice, were studied. Previous data for microbial biomass, nitrogen and carbon contents, and nitrogen mineralization rates suggested that the microbial characteristics of these soils were different. One site received two different treatments: no-till and conventional till perennial ryegrass. The other sites were no-till continuous grass plots at separate locations with different soil types. Community composition was characterized by assessing the natural length heterogeneity in eubacterial sequences amplified from the 5′ domain of the 16S rRNA gene and by determining fatty acid methyl ester (FAME) profiles. We found that LH-PCR results were reproducible. Both methods distinguished the three sites. The most abundant bacterial community members, based on cloned LH-PCR products, were members of the β subclass of the class Proteobacteria, the Cytophaga-Flexibacter-Bacteriodes group, and the high-G+C-content gram-positive bacterial group. Strong correlations were found between LH-PCR results and FAME results. We found that the LH-PCR method is an efficient, reliable, and highly reproducible method that should be a useful tool in future assessments of microbial community composition. PMID:10742258

Circulating metabolomic profile can predict dyslipidemia in HIV patients undergoing antiretroviral therapy.

PubMed

Rodríguez-Gallego, Esther; Gómez, Josep; Domingo, Pere; Ferrando-Martínez, Sara; Peraire, Joaquim; Viladés, Consuelo; Veloso, Sergi; López-Dupla, Miguel; Beltrán-Debón, Raúl; Alba, Verónica; Vargas, Montserrat; Castellano, Alfonso J; Leal, Manuel; Pacheco, Yolanda María; Ruiz-Mateos, Ezequiel; Gutiérrez, Félix; Vidal, Francesc; Rull, Anna

2018-06-01

Dyslipidemia in HIV-infected patients is unique and pathophysiologically associated with host factors, HIV itself and the use of antiretroviral therapy (ART). The use of nuclear magnetic resonance spectroscopy (NMR) provides additional data to conventional lipid measurements concerning the number of lipoprotein subclasses and particle sizes. To investigate the ability of lipoprotein profile, we used a circulating metabolomic approach in a cohort of 103 ART-naive HIV-infected patients, who were initiating non-nucleoside analogue transcriptase inhibitor (NNRTI)-based ART, and we subsequently followed up these patients for 36 months. Univariate and multivariate analyses were performed to evaluate the predictive power of NMR spectroscopy. VLDL-metabolism (including VLDL lipid concentrations, sizes, and particle numbers), total triglycerides and lactate levels resulted in good classifiers of dyslipidemia (AUC 0.903). Total particles/HDL-P ratio was significantly higher in ART-associated dyslipidemia compared to ART-normolipidemia (p = 0.001). Large VLDL-Ps were positively associated with both LDL-triglycerides (ρ 0.682, p < 0.001) and lactate concentrations (ρ 0.416, p < 0.001), the last one a marker of mitochondrial low oxidative capacity. Our data suggest that circulating metabolites have better predictive values for HIV/ART-related dyslipidemia onset than do the biochemical markers associated with conventional lipid measurements. NMR identifies changes in VLDL-P, lactate and LDL-TG as potential clinical markers of baseline HIV-dyslipidemia predisposition. Differences in circulating metabolomics, especially differences in particle size, are indicators of important derangements of mitochondrial function that are linked to ART-related dyslipidemia. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

The succession of microbial community in the organic rich fish-farm sediment during bioremediation by introducing artificially mass-cultured colonies of a small polychaete, Capitella sp. I.

PubMed

Kunihiro, Tadao; Miyazaki, Tomoaki; Uramoto, Yuuta; Kinoshita, Kyoko; Inoue, Akihiro; Tamaki, Sayaka; Hama, Daigo; Tsutsumi, Hiroaki; Ohwada, Kouichi

2008-01-01

We monitored seasonal changes of the abundance and composition of microorganisms in the fish-farm sediment in Kusuura Bay, Amakusa, Japan, using the quinone profiling technique, during bioremediation by introducing cultured colonies of polychaete, Capitella sp. I. In November 2004, approximately 9.2 million cultured worms were transferred to the fish-farm sediment, which increased rapidly, and reached 458.5 gWW/m(2) (528,000 indiv./m(2)) in March 2005. During this fast-increasing period of Capitella, the microbial quinone content of the surface sediment (0-2 cm) also increased markedly, and reached 237 micromol/m(2) in January 2005, although the water temperature decreased to the lowest levels in the year. Particularly, the mole fraction of ubiquinone-10 in total quinones in the sediment, indicating the presence of alpha subclass of Proteobacteria, increased by 9.3%. These facts suggest that the bacterial growth was enhanced markedly by the biological activities of worms in the sediment, and the bacteria played an important role in the decomposition of the organic matter in the sediment.

Epigenetic Regulation of ZBTB18 Promotes Glioblastoma Progression

PubMed Central

Fedele, Vita; Dai, Fangping; Masilamani, Anie Priscilla; Heiland, Dieter Henrik; Kling, Eva; Gätjens-Sanchez, Ana Maria; Ferrarese, Roberto; Platania, Leonardo; Soroush, Doostkam; Kim, Hyunsoo; Nelander, Sven; Weyerbrock, Astrid; Prinz, Marco; Califano, Andrea; Iavarone, Antonio; Bredel, Markus; Carro, Maria Stella

2018-01-01

Glioblastoma (GBM) is comprised of distinct subtypes characterized by their molecular profile. Mesenchymal identity in GBM has been associated with a comparatively unfavorable prognosis, primarily due to inherent resistance of these tumors to current therapies. The identification of molecular determinants of mesenchymal transformation could potentially allow for the discovery of new therapeutic targets. Zinc Finger and BTB Domain Containing 18 (ZBTB18/ZNF238/RP58) is a zinc finger transcriptional repressor with a crucial role in brain development and neuronal differentiation. Here, ZBTB18 is primarily silenced in the mesenchymal subtype of GBM through aberrant promoter methylation. Loss of ZBTB18 contributes to the aggressive phenotype of glioblastoma through regulation of poor prognosis-associated signatures. Restitution of ZBTB18 expression reverses the phenotype and impairs tumor-forming ability. These results indicate that ZBTB18 functions as a tumor suppressor in GBM through the regulation of genes associated with phenotypically aggressive properties. Implications This study characterizes the role of the putative tumor suppressor ZBTB18 and its regulation by promoter hypermethylation, which appears to be a common mechanism to silence ZBTB18 in the mesenchymal subtype of GBM and provides a new mechanistic opportunity to specifically target this tumor subclass. PMID:28512252

Nondestructive identification for red ink entries of seals by Raman and Fourier transform infrared spectrometry.

PubMed

Wang, Xiang-Feng; Yu, Jing; Zhang, Ai-Lan; Zhou, Dai-Wei; Xie, Meng-Xia

2012-11-01

Determination of the red ink entries of seals on documents can provide valuable evidences for solving related crimes, distinguishing the truth of artworks, and so establishment of nondestructive approaches would play a key role in forensic analysis and related aspects. Raman and FT-IR spectroscopy have been applied for analyzing 105 kinds of red ink entries on documents. The dye components of the ink entries were identified by FT-Raman and confocal Raman microspectroscopy, and then the ink entries were classified into four groups based on these dye components. The ink entries were further discriminated by their FT-IR spectra according to adsorption peaks of the main components, the relative intensities of the characteristic bands and the profiles of the spectra. The results showed that 70 ink entries out of 105 have been individually identified and the remaining 35 ink entries can be divided into 13 subclasses. Combination of Raman and FT-IR spectroscopic methods can provide a powerful nondestructive discriminating tool for identification of the red ink entries of seals on papers. These approaches would have potential application in archeology, art and forensic science. Copyright © 2012 Elsevier B.V. All rights reserved.

A lineage CLOUD for neoblasts.

PubMed

Tran, Thao Anh; Gentile, Luca

2018-05-10

In planarians, pluripotency can be studied in vivo in the adult animal, making these animals a unique model system where pluripotency-based regeneration (PBR)-and its therapeutic potential-can be investigated. This review focuses on recent findings to build a cloud model of fate restriction likelihood for planarian stem and progenitor cells. Recently, a computational approach based on functional and molecular profiling at the single cell level was proposed for human hematopoietic stem cells. Based on data generated both in vivo and ex vivo, we hypothesized that planarian stem cells could acquire multiple direction lineage biases, following a "badlands" landscape. Instead of a discrete tree-like hierarchy, where the potency of stem/progenitor cells reduces stepwise, we propose a Continuum of LOw-primed UnDifferentiated Planarian Stem/Progenitor Cells (CLOUD-PSPCs). Every subclass of neoblast/progenitor cells is a cloud of likelihood, as the single cell transcriptomics data indicate. The CLOUD-HSPCs concept was substantiated by in vitro data from cell culture; therefore, to confirm the CLOUD-PSPCs model, the planarian community needs to develop new tools, like live cell tracking. Future studies will allow a deeper understanding of PBR in planarian, and the possible implications for regenerative therapies in human. Copyright © 2018 Elsevier Ltd. All rights reserved.

The barrier function of organotypic non-melanoma skin cancer models.

PubMed

Zoschke, Christian; Ulrich, Martina; Sochorová, Michaela; Wolff, Christopher; Vávrová, Kateřina; Ma, Nan; Ulrich, Claas; Brandner, Johanna M; Schäfer-Korting, Monika

2016-07-10

Non-melanoma skin cancer (NMSC) is the most frequent human cancer with continuously rising incidences worldwide. Herein, we investigated the molecular basis for the impaired skin barrier function of organotypic NMSC models. We unraveled disturbed epidermal differentiation by reflectance confocal microscopy and histopathological evaluation. While the presence of claudin-4 and occludin were distinctly reduced, zonula occludens protein-1 was more wide-spread, and claudin-1 was heterogeneously distributed within the NMSC models compared with normal reconstructed human skin. Moreover, the cancer altered stratum corneum lipid packing and profile with decreased cholesterol content, increased phospholipid amount, and altered ceramide subclasses. These alterations contributed to increased surface pH and to 1.5 to 2.6-fold enhanced caffeine permeability of the NMSC models. Three topical applications of ingenol mebutate gel (0.015%) caused abundant epidermal cell necrosis, decreased Ki-67 indices, and increased lactate dehydrogenase activity. Taken together, our study provides new biological insights into the microenvironment of organotypic NMSC models, improves the understanding of the disease model by revealing causes for impaired skin barrier function in NMSC models at the molecular level, and fosters human cell-based approaches in preclinical drug evaluation. Copyright © 2016 Elsevier B.V. All rights reserved.

Rogue waves in the multicomponent Mel'nikov system and multicomponent Schrödinger-Boussinesq system

NASA Astrophysics Data System (ADS)

Sun, Baonan; Lian, Zhan

2018-02-01

By virtue of the bilinear method and the KP hierarchy reduction technique, exact explicit rational solutions of the multicomponent Mel'nikov equation and the multicomponent Schrödinger-Boussinesq equation are constructed, which contain multicomponent short waves and single-component long wave. For the multicomponent Mel'nikov equation, the fundamental rational solutions possess two different behaviours: lump and rogue wave. It is shown that the fundamental (simplest) rogue waves are line localised waves which arise from the constant background with a line profile and then disappear into the constant background again. The fundamental line rogue waves can be classified into three: bright, intermediate and dark line rogue waves. Two subclasses of non-fundamental rogue waves, i.e., multirogue waves and higher-order rogue waves are discussed. The multirogue waves describe interaction of several fundamental line rogue waves, in which interesting wave patterns appear in the intermediate time. Higher-order rogue waves exhibit dynamic behaviours that the wave structures start from lump and then retreat back to it. Moreover, by taking the parameter constraints further, general higher-order rogue wave solutions for the multicomponent Schrödinger-Boussinesq system are generated.

An ultracentrifugation analysis of two hundred fish genomes.

PubMed

Bucciarelli, Giuseppe; Bernardi, Giacomo; Bernardi, Giorgio

2002-08-07

The goal of this study was to provide a comprehensive view of the compositional characteristics of fish genomes. We therefore expanded the number of fish species that we had explored so far in their DNAs by analytical ultracentrifugation in CsCl density gradient from 122 to 201. This study included representatives from three out of nine orders of Elasmobranchs (sharks and rays), both orders of dipnoan lungfishes, and both orders of chondrosteans (sturgeons and bichirs). We also studied 19 out of 38 teleostean orders, which represent all but four (minor) superorders of the subdivision Teleostei, a group comprising about 23,600 species (96% of all extant fishes). This leaves for further studies two subclasses, Holocephali (chimaeras), and Coelacanthimorpha (gombessas). In spite of this substantial increase in the number of species and orders analysed, all average properties (the modal buoyant density, rho(0), the average buoyant density, , the CsCl profile asymmetry, A, and the compositional heterogeneity, H), and all their ranges were unchanged compared to a previous study [J. Mol. Evol. 31 (1990) 265]. This suggests that, in all likelihood, the properties reported in the present paper can be considered as generally valid for all fish genomes.

Methylopila capsulata gen. nov., sp. nov., a novel non-pigmented aerobic facultatively methylotrophic bacterium.

PubMed

Doronina, N V; Trotsenko, Y A; Krausova, V I; Boulygina, E S; Tourova, T P

1998-10-01

A new genus, Methylopila, and one new species are described for a group of seven strains of facultatively methylotrophic bacteria with the serine pathway of C1 assimilation. These bacteria are aerobic, Gram-negative, non-spore--forming, motile, colourless rods that multiply by binary fission. Their DNA base content ranges from 66 to 70 mol % G + C. Their cellular fatty acid profile consists primarily of C18:1 omega 7 cis-vaccenic and C19:0 cyclopropane acids. The major hydroxy acid is 3-OH C14:0. The main ubiquinone is Q-10. The dominant cellular phospholipids are phosphatidylethanolamine and phosphatidylcholine. The new isolates have a low level of DNA-DNA homology (5-10%) with the type strains of the serine pathway methylobacteria belonging to the genera Methylobacterium, Aminobacter, Hyphomicrobium and Methylorhabdus. Another approach, involving 16S rRNA gene sequence analysis of strain IM1T, has shown that the new isolates represent a separate branch within the alpha-2 subclass of the Proteobacteria. The type species of the new genus is Methylopila capsulata sp. nov., with the type strain IM1T (= VKM B-1606T).

Manipulating the sleep-wake cycle and circadian rhythms to improve clinical management of major depression

PubMed Central

2013-01-01

Background Clinical psychiatry has always been limited by the lack of objective tests to substantiate diagnoses and a lack of specific treatments that target underlying pathophysiology. One area in which these twin failures has been most frustrating is major depression. Due to very considerable progress in the basic and clinical neurosciences of sleep-wake cycles and underlying circadian systems this situation is now rapidly changing. Discussion The development of specific behavioral or pharmacological strategies that target these basic regulatory systems is driving renewed clinical interest. Here, we explore the extent to which objective tests of sleep-wake cycles and circadian function - namely, those that measure timing or synchrony of circadian-dependent physiology as well as daytime activity and nighttime sleep patterns - can be used to identify a sub-class of patients with major depression who have disturbed circadian profiles. Summary Once this unique pathophysiology is characterized, a highly personalized treatment plan can be proposed and monitored. New treatments will now be designed and old treatments re-evaluated on the basis of their effects on objective measures of sleep-wake cycles, circadian rhythms and related metabolic systems. PMID:23521808

Procyanidin content and variation in some commonly consumed foods.

PubMed

Hammerstone, J F; Lazarus, S A; Schmitz, H H

2000-08-01

Procyanidins are a subclass of flavonoids found in commonly consumed foods that have attracted increasing attention due to their potential health benefits. However, little is known regarding their dietary intake levels because detailed quantitative information on the procyanidin profiles present in many food products is lacking. Therefore, the procyanidin content of red wine, chocolate, cranberry juice and four varieties of apples has been determined. On average, chocolate and apples contained the largest procyanidin content per serving (164.7 and 147.1 mg, respectively) compared with red wine and cranberry juice (22.0 and 31.9 mg, respectively). However, the procyanidin content varied greatly between apple samples (12.3-252.4 mg/serving) with the highest amounts on average observed for the Red Delicious (207.7 mg/serving) and Granny Smith (183.3 mg/serving) varieties and the lowest amounts in the Golden Delicious (92.5 mg/serving) and McIntosh (105.0 mg/serving) varieties. The compositional data reported herein are important for the initial understanding of which foods contribute most to the dietary intake of procyanidins and may be used to compile a database necessary to infer epidemiological relationships to health and disease.

Isolation and Properties of Floral Defensins from Ornamental Tobacco and Petunia1

PubMed Central

Lay, Fung T.; Brugliera, Filippa; Anderson, Marilyn A.

2003-01-01

The flowers of the solanaceous plants ornamental tobacco (Nicotiana alata) and petunia (Petunia hybrida) produce high levels of defensins during the early stages of development. In contrast to the well-described seed defensins, these floral defensins are produced as precursors with C-terminal prodomains of 27 to 33 amino acids in addition to a typical secretion signal peptide and central defensin domain of 47 or 49 amino acids. Defensins isolated from N. alata and petunia flowers lack the C-terminal domain, suggesting that it is removed during or after transit through the secretory pathway. Immunogold electron microscopy has been used to demonstrate that the N. alata defensin is deposited in the vacuole. In addition to the eight canonical cysteine residues that define the plant defensin family, the two petunia defensins have an extra pair of cysteines that form a fifth disulfide bond and hence define a new subclass of this family of proteins. Expression of the N. alata defensin NaD1 is predominantly flower specific and is most active during the early stages of flower development. NaD1 transcripts accumulate in the outermost cell layers of petals, sepals, anthers, and styles, consistent with a role in protection of the reproductive organs against potential pathogens. The floral defensins inhibit the growth of Botrytis cinerea and Fusarium oxysporum in vitro, providing further support for a role in protection of floral tissues against pathogen invasion. PMID:12644678

The hydrologic implications of alternative prioritizations of landscape-scale geographically isolated wetlands conservation

NASA Astrophysics Data System (ADS)

Evenson, G. R.; Golden, H. E.; Lane, C.; Mclaughlin, D. L.; D'Amico, E.

2016-12-01

Geographically isolated wetlands (GIWs), defined as upland embedded wetlands, provide an array of ecosystem goods and services. Wetland conservation efforts aim to protect GIWs in the face of continued threats from anthropogenic activities. Given limited conservation resources, there is a critical need for methods capable of evaluating the watershed-scale hydrologic implications of alternative approaches to GIW conservation. Further, there is a need for methods that quantify the watershed-scale aggregate effects of GIWs to determine their regulatory status within the United States. We applied the Soil and Water Assessment Tool (SWAT), a popular watershed-scale hydrologic model, to represent the 1,700 km2 Pipestem Creek watershed in North Dakota, USA. We modified the model to incorporate an improved representation of GIW hydrologic processes via hydrologic response unit (HRU) redefinition and modifications to the model source code. We then used the model to evaluate the hydrologic effects of alternative approaches to GIW conservation prioritization by simulating the destruction/removal of GIWs by sub-classes defined by their relative position within the simulated fill-spill GIW network and their surface area characteristics. We evaluated the alternative conservation approaches as impacting (1) simulated streamflow at the Pipestem Creek watershed outlet; (2) simulated water-levels within the GIWs; and (3) simulated hydrologic connections between the GIWs. Our approach to modifying SWAT and evaluating alternative GIW conservation strategies may be replicated in different watersheds and physiographic regions to aid the development of GIW conservation priorities.

47 CFR 32.2321 - Customer premises wiring.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 47 Telecommunication 2 2010-10-01 2010-10-01 false Customer premises wiring. 32.2321 Section 32... Customer premises wiring. (a) This account shall include all amounts transferred from the former Account 232, Station Connections, inside wiring subclass. (b) Embedded Customer Premises Wiring is that...

Damage Detection and Mitigation in Open Collaboration Applications

ERIC Educational Resources Information Center

West, Andrew G.

2013-01-01

Collaborative functionality is changing the way information is amassed, refined, and disseminated in online environments. A subclass of these systems characterized by "open collaboration" uniquely allow participants to "modify" content with low barriers-to-entry. A prominent example and our case study, English Wikipedia,…

37 CFR 1.76 - Application data sheet.

Code of Federal Regulations, 2010 CFR

2010-07-01

... includes the correspondence address, which may be indicated by reference to a customer number, to which... title of the invention, a suggested classification, by class and subclass, the Technology Center to... application, the type of application (e.g., utility, plant, design, reissue, provisional), whether the...

Assignment of EC Numbers to Enzymatic Reactions with Reaction Difference Fingerprints

PubMed Central

Hu, Qian-Nan; Zhu, Hui; Li, Xiaobing; Zhang, Manman; Deng, Zhe; Yang, Xiaoyan; Deng, Zixin

2012-01-01

The EC numbers represent enzymes and enzyme genes (genomic information), but they are also utilized as identifiers of enzymatic reactions (chemical information). In the present work (ECAssigner), our newly proposed reaction difference fingerprints (RDF) are applied to assign EC numbers to enzymatic reactions. The fingerprints of reactant molecules minus the fingerprints of product molecules will generate reaction difference fingerprints, which are then used to calculate reaction Euclidean distance, a reaction similarity measurement, of two reactions. The EC number of the most similar training reaction will be assigned to an input reaction. For 5120 balanced enzymatic reactions, the RDF with a fingerprint length at 3 obtained at the sub-subclass, subclass, and main class level with cross-validation accuracies of 83.1%, 86.7%, and 92.6% respectively. Compared with three published methods, ECAssigner is the first fully automatic server for EC number assignment. The EC assignment system (ECAssigner) is freely available via: http://cadd.whu.edu.cn/ecassigner/. PMID:23285222

Editing of mouse and human immunoglobulin genes by CRISPR-Cas9 system.

PubMed

Cheong, Taek-Chin; Compagno, Mara; Chiarle, Roberto

2016-03-09

Applications of the CRISPR-Cas9 system to edit the genome have widely expanded to include DNA gene knock-out, deletions, chromosomal rearrangements, RNA editing and genome-wide screenings. Here we show the application of CRISPR-Cas9 technology to edit the mouse and human immunoglobulin (Ig) genes. By delivering Cas9 and guide-RNA (gRNA) with retro- or lenti-virus to IgM(+) mouse B cells and hybridomas, we induce class-switch recombination (CSR) of the IgH chain to the desired subclass. Similarly, we induce CSR in all human B cell lines tested with high efficiency to targeted IgH subclass. Finally, we engineer mouse hybridomas to secrete Fab' fragments instead of the whole Ig. Our results indicate that Ig genes in mouse and human cells can be edited to obtain any desired IgH switching helpful to study the biology of normal and lymphoma B cells. We also propose applications that could transform the technology of antibody production.

Plasmid-mediated resistance to protein biosynthesis inhibitors in staphylococci.

PubMed

Schwarz, Stefan; Fessler, Andrea T; Hauschild, Tomasz; Kehrenberg, Corinna; Kadlec, Kristina

2011-12-01

Protein biosynthesis inhibitors (PBIs) represent powerful antimicrobial agents for the control of bacterial infections. In staphylococci, numerous resistance genes are known to be involved in resistance to PBIs, most of which mediate resistance to a specific class/subclass of PBIs, though a few genes do confer a multidrug resistance phenotype-up to five classes/subclasses of PBIs. Plasmids play a key role in the dissemination of PBI resistance among staphylococci, as they primarily carry plasmid-borne PBI resistance genes; however, plasmids also can be vectors for transposon-borne PBI resistance genes. Small plasmids that carry single PBI resistance genes are widespread among staphylococci of human and animal origin. Various mechanisms exist by which they can recombine, form cointegrates, or integrate into chromosomal DNA or larger plasmids. We provide an overview of the current knowledge of plasmid-mediated PBI resistance in staphylococci, with particular reference to the currently known PBI resistance genes, their association with mobile genetic elements, and the recombination/integration processes that control their mobility. © 2011 New York Academy of Sciences.

Search for Type Ia supernova NUV-optical subclasses

NASA Astrophysics Data System (ADS)

Cinabro, David; Scolnic, Daniel; Kessler, Richard; Li, Ashley; Miller, Jake

2017-04-01

In response to a recently reported observation of evidence for two classes of Type Ia supernovae (SNe Ia) distinguished by their brightness in the rest-frame near-ultraviolet (NUV), we search for the phenomenon in publicly available light-curve data. We use the SNANA supernova analysis package to simulate SN Ia light curves in the Sloan Digital Sky Survey (SDSS) Supernova Search and the Supernova Legacy Survey (SNLS) with a model of two distinct ultraviolet classes of SNe Ia and a conventional model with a single broad distribution of SN-Ia ultraviolet brightnesses. We compare simulated distributions of rest-frame colours with these two models to those observed in 158 SNe Ia in the SDSS and SNLS data. The SNLS sample of 99 SNe Ia is in clearly better agreement with a model with one class of SN Ia light curves and shows no evidence for distinct NUV sub-classes. The SDSS sample of 59 SNe Ia with poorer colour resolution does not distinguish between the two models.

Heterogeneity of humoral immune abnormalities in children with Nijmegen breakage syndrome: an 8-year follow-up study in a single centre

PubMed Central

Gregorek, H; Chrzanowska, K H; Michałkiewicz, J; Syczewska, M; Madaliński, K

2002-01-01

During an 8-year period of observation, defects of immune responses were characterized and monitored in 40 of 50 Polish children with Nijmegen breakage syndrome referred to the Children's Memorial Health Institute in Warsaw. The following parameters were determined at diagnosis: (1) concentrations of serum IgM, IgG, IgA; (2) concentrations of IgG subclasses; and (3) lymphocyte subpopulations. In addition, naturally acquired specific antibodies against Streptococcus pneumoniae were determined in 20 patients with a history of recurrent respiratory infections. During follow-up, total serum immunoglobulins and IgG subclasses were monitored systematically in 17 patients who did not receive immunomodulatory therapy. Moreover, anti-HBs antibody response was measured after vaccination of 20 children against HBV. We found that the immune deficiency in NBS is profound, highly variable, with a tendency to progress over time. Systematic monitoring of the humoral response, despite good clinical condition, is essential for early medical intervention. PMID:12390322

VizieR Online Data Catalog: Abundances of 8 RR Lyrae subclass C variable stars (Govea+, 2014)

NASA Astrophysics Data System (ADS)

Govea, J.; Gomez, T.; Preston, G. W.; Sneden, C.

2016-02-01

We chose 10 candidate RR Lyrae variable stars of subclass c (RRc) stars for spectroscopic observation. Many of these stars were first identified as RRc variables by the All Sky Automated Survey (ASAS) of Pojmanski 2003 (cat. II/264). The target star list included ASAS 144154-0324.7 and ASAS 204440-2402.7. But our spectroscopic study suggest that these two stars are probably W UMa binaries instead of RR Lyrae stars Our spectra were obtained with the echelle spectrograph of the du Pont 2.5m telescope at the Las Campanas Observatory. Four observing runs during 2009-2010 were partly devoted to this project. The spectrograph was used with the 1.5*4'' entrance slit, which translates to a resolving power of R=λ/Δλ~27000 at the MgI b lines near 5180Å. The total continuous wavelength coverage of the spectra was 3500-9000Å. (6 data files).

Discrimination and supervised classification of volcanic flows of the Puna-Altiplano, Central Andes Mountains using Landsat TM data

NASA Technical Reports Server (NTRS)

Mcbride, J. H.; Fielding, E. J.; Isacks, B. L.

1987-01-01

Landsat Thematic Mapper (TM) images of portions of the Central Andean Puna-Altiplano volcanic belt have been tested for the feasibility of discriminating individual volcanic flows using supervised classifications. This technique distinguishes volcanic rock classes as well as individual phases (i.e., relative age groups) within each class. The spectral signature of a volcanic rock class appears to depend on original texture and composition and on the degree of erosion, weathering, and chemical alteration. Basalts and basaltic andesite stand out as a clearly distinguishable class. The age dependent degree of weathering of these generally dark volcanic rocks can be correlated with reflectance: older rocks have a higher reflectance. On the basis of this relationship, basaltaic lava flows can be separated into several subclasses. These individual subclasses would correspond to mappable geologic units on the ground at a reconnaissance scale. The supervised classification maps are therefore useful for establishing a general stratigraphic framework for later detailed surface mapping of volcanic sequences.

Accidental inflation from Kähler uplifting

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ben-Dayan, Ido; Westphal, Alexander; Wieck, Clemens

2014-03-01

We analyze the possibility of realizing inflation with a subsequent dS vacuum in the Käahler uplifting scenario. The inclusion of several quantum corrections to the 4d effective action evades previous no-go theorems and allows for construction of simple and successful models of string inflation. The predictions of several benchmark models are in accord with current observations, i.e., a red spectral index, negligible non-gaussianity, and spectral distortions similar to the simplest models of inflation. A particularly interesting subclass of models are ''left-rolling'' ones, where the overall volume of the compactified dimensions shrinks during inflation. We call this phenomenon ''inflation by deflation''more » (IBD), where deflation refers to the internal manifold. This subclass has the appealing features of being insensitive to initial conditions, avoiding the overshooting problem, and allowing for observable running α ∼ 0.012 and enhanced tensor-to-scalar ratio r ∼ 10{sup −5}. The latter results differ significantly from many string inflation models.« less

Aerogenic vaccination with a Burkholderia mallei auxotroph protects against aerosol-initiated glanders in mice.

PubMed

Ulrich, Ricky L; Amemiya, Kei; Waag, David M; Roy, Chad J; DeShazer, David

2005-03-14

Burkholderia mallei is an obligate mammalian pathogen that causes the zoonotic disease glanders. Two live attenuated B. mallei strains, a capsule mutant and a branched-chain amino acid auxotroph, were evaluated for use as vaccines against aerosol-initiated glanders in mice. Animals were aerogenically vaccinated and serum samples were obtained before aerosol challenge with a high-dose (>300 times the LD50) of B. mallei ATCC 23344. Mice vaccinated with the capsule mutant developed a Th2-like Ig subclass antibody response and none survived beyond 5 days. In comparison, the auxotrophic mutant elicited a Th1-like Ig subclass antibody response and 25% of the animals survived for 1 month postchallenge. After a low-dose (5 times the LD50) aerosol challenge, the survival rates of auxotroph-vaccinated and unvaccinated animals were 50 and 0%, respectively. Thus, live attenuated strains that promote a Th1-like Ig response may serve as promising vaccine candidates against aerosol infection with B. mallei.

Insights into the history of the legume-betaproteobacterial symbiosis.

PubMed

Angus, Annette A; Hirsch, Ann M

2010-01-01

The interaction between legumes and rhizobia has been well studied in the context of a mutualistic, nitrogen-fixing symbiosis. The fitness of legumes, including important agricultural crops, is enhanced by the plants' ability to develop symbiotic associations with certain soil bacteria that fix atmospheric nitrogen into a utilizable form, namely, ammonia, via a chemical reaction that only bacteria and archaea can perform. Of the bacteria, members of the alpha subclass of the protebacteria are the best-known nitrogen-fixing symbionts of legumes. Recently, members of the beta subclass of the proteobacteria that induce nitrogen-fixing nodules on legume roots in a species-specific manner have been identified. In this issue, Bontemps et al. reveal that not only are these newly identified rhizobia novel in shifting the paradigm of our understanding of legume symbiosis, but also, based on symbiotic gene phylogenies, have a history that is both ancient and stable. Expanding our understanding of novel plant growth promoting rhizobia will be a valuable resource for incorporating alternative strategies of nitrogen fixation for enhancing plant growth.

Immunological studies on bee-keepers: specific IgG and subclass typing IgG against bee venom and bee venom components.

PubMed

Urbanek, R; Forster, J; Ziupa, J; Karitzky, D

1980-11-17

Specific IgE antibodies against bee venom and its components were studied in 23 bee-keepers. The highest IgG serum levels were observed for whole bee venom followed by phospholipase A. The serum levels of specific IgG antibodies against melittin and MCD-peptide were lower, the lowest serum levels being observed for apamin. After a 5 month absence from bee-keeping a fall in the serum levels of IgG antibodies was observed in all the bee-keepers studied. The investigation of the IgG subclass antibodies 1-4 against bee venom and phospholipase A demonstrated the highest serum levels for IgG 4 and IgG 2, the lowest levels were observed for IgG 1. The lowest IgG serum levels were associated with the least effective protection to bee stings. These findings support the concept that specific IgG antibodies prevent the development of allergic symptoms after bee sting.

A Spectroscopic Catalog of Nearby, High Proper Motion M subdwarfs

NASA Astrophysics Data System (ADS)

Hejazi, Neda; Lepine, Sebastien; Homeier, Derek

2018-01-01

We present a catalog of 350 metal-poor M subdwarfs, most of them likely from the local Galactic halo population, assembled from medium-resolution observations made at the MDM observatory. All objects are high proper motion stars, with 257 of them having proper motions > 0.4"/yr. We have identified the brightest prototypes for each bin of a grid of 14 spectral subtypes (M0, M0.5, M1, … M6.5) and 9 metallicity bins that go from the moderately metal-poor subdwarfs (sdM), to the more metal-poor extreme subdwarfs (esdM), to the most metal-poor ultra subdwarfs (usdM), each of which is subdivided into three finer metallicity subclasses. The spectral classification by subtype and metallicity class has been determined by a template-fit method, and confirmed by synthetic-model fitting using the BT-Settl spectral grid. We provide the list of the brightest prototypes for each subtype/subclass, as a guide for future high-resolution surveys of low-mass, metal-poor stars.

Mass Spectrometric Characterization of Benzoxazinoid Glycosides from Rhizopus-Elicited Wheat (Triticum aestivum) Seedlings.

PubMed

de Bruijn, Wouter J C; Vincken, Jean-Paul; Duran, Katharina; Gruppen, Harry

2016-08-17

Benzoxazinoids function as defense compounds and have been suggested to possess health-promoting effects. In this work, the mass spectrometric behavior of benzoxazinoids from the classes benzoxazin-3-ones (with subclasses lactams, hydroxamic acids, and methyl derivatives) and benzoxazolinones was studied. Wheat seeds were germinated with simultaneous elicitation by Rhizopus. The seedling extract was screened for the presence of benzoxazinoid (glycosides) using reversed-phase ultra-high-performance liquid chromatography with photodiode array detection coupled in line to multiple-stage mass spectrometry (RP-UHPLC-PDA-MS(n)). Benzoxazin-3-ones from the different subclasses showed distinctly different ionization and fragmentation behaviors. These features were incorporated into a newly proposed decision guideline to aid the classification of benzoxazinoids. Glycosides of the methyl derivative 2-hydroxy-4-methoxy-1,4-benzoxazin-3-one were tentatively identified for the first time in wheat. We conclude that wheat seedlings germinated with simultaneous fungal elicitation contain a diverse array of benzoxazinoids, mainly constituted by benzoxazin-3-one glycosides.

Systematic profiling and comparison of the lipidomes from Panax ginseng, P. quinquefolius, and P. notoginseng by ultrahigh performance supercritical fluid chromatography/high-resolution mass spectrometry and ion mobility-derived collision cross section measurement.

PubMed

Shi, Xiaojian; Yang, Wenzhi; Qiu, Shi; Hou, Jinjun; Wu, Wanying; Guo, Dean

2018-05-04

Lipidomics currently is still confronted with challenges from chromatographic separation and lipids identification. Here we report a lipidomics platform by integrating ultrahigh performance supercritical fluid chromatography/quadrupole time-of-flight mass spectrometry (UHPSFC/QTOF-MS) and collision cross section (CCS) measurement using ion mobility spectroscopy/time-of-flight mass spectrometry (IMS/QTOF-MS), aiming to enhance the profiling performance and identification reliability of lipids. The lipidomes extracted from three congeneric Panax species (P. ginseng, P. quinquefolius, and P. notoginseng) by methyl tert-butyl ether are comprehensively profiled and compared by use of this platform. A potent UHPSFC/QTOF-MS approach was developed on a 1.7-μm particles packed Torus 2-PIC column using CH 3 OH (in CO 2 ) as a modifier and CH 3 OH/0.2 mM ammonium acetate as the makeup liquid, enabling well resolution of six lipid subclasses by both positive and negative MS E modes. In contrast to the reversed-phase chromatography, "normal-phase" like elution order and better resolution of polar lipids and some lipid isomers were achieved by UHPSFC separation. Pattern recognition chemometric analysis of 60 batches of Ginseng samples ultimately unveiled 24 lipid markers, of which triacylglycerols were the most important. Aside from the automated MS database searching against HMDB and LIPID MAPS, the application of CCS retrieval or CCS prediction improved lipid identification by reducing the possible hits. In conclusion, this integral platform can significantly improve the chromatographic separation and the reliability of lipids identification in lipidomics studies. It is the first report that systematically compares the lipidomic difference of three reputable Panax species, providing useful information for their quality control in addition to ginsenoside analysis. Copyright © 2018 Elsevier B.V. All rights reserved.

Whole genome sequencing in support of wellness and health maintenance.

PubMed

Patel, Chirag J; Sivadas, Ambily; Tabassum, Rubina; Preeprem, Thanawadee; Zhao, Jing; Arafat, Dalia; Chen, Rong; Morgan, Alexander A; Martin, Gregory S; Brigham, Kenneth L; Butte, Atul J; Gibson, Greg

2013-01-01

Whole genome sequencing is poised to revolutionize personalized medicine, providing the capacity to classify individuals into risk categories for a wide range of diseases. Here we begin to explore how whole genome sequencing (WGS) might be incorporated alongside traditional clinical evaluation as a part of preventive medicine. The present study illustrates novel approaches for integrating genotypic and clinical information for assessment of generalized health risks and to assist individuals in the promotion of wellness and maintenance of good health. Whole genome sequences and longitudinal clinical profiles are described for eight middle-aged Caucasian participants (four men and four women) from the Center for Health Discovery and Well Being (CHDWB) at Emory University in Atlanta. We report multivariate genotypic risk assessments derived from common variants reported by genome-wide association studies (GWAS), as well as clinical measures in the domains of immune, metabolic, cardiovascular, musculoskeletal, respiratory, and mental health. Polygenic risk is assessed for each participant for over 100 diseases and reported relative to baseline population prevalence. Two approaches for combining clinical and genetic profiles for the purposes of health assessment are then presented. First we propose conditioning individual disease risk assessments on observed clinical status for type 2 diabetes, coronary artery disease, hypertriglyceridemia and hypertension, and obesity. An approximate 2:1 ratio of concordance between genetic prediction and observed sub-clinical disease is observed. Subsequently, we show how more holistic combination of genetic, clinical and family history data can be achieved by visualizing risk in eight sub-classes of disease. Having identified where their profiles are broadly concordant or discordant, an individual can focus on individual clinical results or genotypes as they develop personalized health action plans in consultation with a health partner or coach. The CHDWB will facilitate longitudinal evaluation of wellness-focused medical care based on comprehensive self-knowledge of medical risks.

Whole genome sequencing in support of wellness and health maintenance

PubMed Central

2013-01-01

Background Whole genome sequencing is poised to revolutionize personalized medicine, providing the capacity to classify individuals into risk categories for a wide range of diseases. Here we begin to explore how whole genome sequencing (WGS) might be incorporated alongside traditional clinical evaluation as a part of preventive medicine. The present study illustrates novel approaches for integrating genotypic and clinical information for assessment of generalized health risks and to assist individuals in the promotion of wellness and maintenance of good health. Methods Whole genome sequences and longitudinal clinical profiles are described for eight middle-aged Caucasian participants (four men and four women) from the Center for Health Discovery and Well Being (CHDWB) at Emory University in Atlanta. We report multivariate genotypic risk assessments derived from common variants reported by genome-wide association studies (GWAS), as well as clinical measures in the domains of immune, metabolic, cardiovascular, musculoskeletal, respiratory, and mental health. Results Polygenic risk is assessed for each participant for over 100 diseases and reported relative to baseline population prevalence. Two approaches for combining clinical and genetic profiles for the purposes of health assessment are then presented. First we propose conditioning individual disease risk assessments on observed clinical status for type 2 diabetes, coronary artery disease, hypertriglyceridemia and hypertension, and obesity. An approximate 2:1 ratio of concordance between genetic prediction and observed sub-clinical disease is observed. Subsequently, we show how more holistic combination of genetic, clinical and family history data can be achieved by visualizing risk in eight sub-classes of disease. Having identified where their profiles are broadly concordant or discordant, an individual can focus on individual clinical results or genotypes as they develop personalized health action plans in consultation with a health partner or coach. Conclusion The CHDWB will facilitate longitudinal evaluation of wellness-focused medical care based on comprehensive self-knowledge of medical risks. PMID:23806097

Humoral and Cell-Mediated Immune Responses to Alternate Booster Schedules of Anthrax Vaccine Adsorbed in Humans

PubMed Central

Sabourin, Carol L.; Schiffer, Jarad M.; Niemuth, Nancy A.; Semenova, Vera A.; Li, Han; Rudge, Thomas L.; Brys, April M.; Mittler, Robert S.; Ibegbu, Chris C.; Wrammert, Jens; Ahmed, Rafi; Parker, Scott D.; Babcock, Janiine; Keitel, Wendy; Poland, Gregory A.; Keyserling, Harry L.; El Sahly, Hana; Jacobson, Robert M.; Marano, Nina; Plikaytis, Brian D.; Wright, Jennifer G.

2016-01-01

Protective antigen (PA)-specific antibody and cell-mediated immune (CMI) responses to annual and alternate booster schedules of anthrax vaccine adsorbed (AVA; BioThrax) were characterized in humans over 43 months. Study participants received 1 of 6 vaccination schedules: a 3-dose intramuscular (IM) priming series (0, 1, and 6 months) with a single booster at 42 months (4-IM); 3-dose IM priming with boosters at 18 and 42 months (5-IM); 3-dose IM priming with boosters at 12, 18, 30, and 42 months (7-IM); the 1970 licensed priming series of 6 doses (0, 0.5, 1, 6, 12, and 18 months) and two annual boosters (30 and 42 months) administered either subcutaneously (SQ) (8-SQ) or IM (8-IM); or saline placebo control at all eight time points. Antibody response profiles included serum anti-PA IgG levels, subclass distributions, avidity, and lethal toxin neutralization activity (TNA). CMI profiles included frequencies of gamma interferon (IFN-γ)- and interleukin 4 (IL-4)-secreting cells and memory B cells (MBCs), lymphocyte stimulation indices (SI), and induction of IFN-γ, IL-2, IL-4, IL-6, IL-1β, and tumor necrosis factor alpha (TNF-α) mRNA. All active schedules elicited high-avidity PA-specific IgG, TNA, MBCs, and T cell responses with a mixed Th1-Th2 profile and Th2 dominance. Anti-PA IgG and TNA were highly correlated (e.g., month 7, r2 = 0.86, P < 0.0001, log10 transformed) and declined in the absence of boosters. Boosters administered IM generated the highest antibody responses. Increasing time intervals between boosters generated antibody responses that were faster than and superior to those obtained with the final month 42 vaccination. CMI responses to the 3-dose IM priming remained elevated up to 43 months. (This study has been registered at ClinicalTrials.gov under registration no. NCT00119067.) PMID:26865594

Metabolomic Profiling of Statin Use and Genetic Inhibition of HMG-CoA Reductase.

PubMed

Würtz, Peter; Wang, Qin; Soininen, Pasi; Kangas, Antti J; Fatemifar, Ghazaleh; Tynkkynen, Tuulia; Tiainen, Mika; Perola, Markus; Tillin, Therese; Hughes, Alun D; Mäntyselkä, Pekka; Kähönen, Mika; Lehtimäki, Terho; Sattar, Naveed; Hingorani, Aroon D; Casas, Juan-Pablo; Salomaa, Veikko; Kivimäki, Mika; Järvelin, Marjo-Riitta; Davey Smith, George; Vanhala, Mauno; Lawlor, Debbie A; Raitakari, Olli T; Chaturvedi, Nish; Kettunen, Johannes; Ala-Korpela, Mika

2016-03-15

Statins are first-line therapy for cardiovascular disease prevention, but their systemic effects across lipoprotein subclasses, fatty acids, and circulating metabolites remain incompletely characterized. This study sought to determine the molecular effects of statin therapy on multiple metabolic pathways. Metabolic profiles based on serum nuclear magnetic resonance metabolomics were quantified at 2 time points in 4 population-based cohorts from the United Kingdom and Finland (N = 5,590; 2.5 to 23.0 years of follow-up). Concentration changes in 80 lipid and metabolite measures during follow-up were compared between 716 individuals who started statin therapy and 4,874 persistent nonusers. To further understand the pharmacological effects of statins, we used Mendelian randomization to assess associations of a genetic variant known to mimic inhibition of HMG-CoA reductase (the intended drug target) with the same lipids and metabolites for 27,914 individuals from 8 population-based cohorts. Starting statin therapy was associated with numerous lipoprotein and fatty acid changes, including substantial lowering of remnant cholesterol (80% relative to low-density lipoprotein cholesterol [LDL-C]), but only modest lowering of triglycerides (25% relative to LDL-C). Among fatty acids, omega-6 levels decreased the most (68% relative to LDL-C); other fatty acids were only modestly affected. No robust changes were observed for circulating amino acids, ketones, or glycolysis-related metabolites. The intricate metabolic changes associated with statin use closely matched the association pattern with rs12916 in the HMGCR gene (R(2) = 0.94, slope 1.00 ± 0.03). Statin use leads to extensive lipid changes beyond LDL-C and appears efficacious for lowering remnant cholesterol. Metabolomic profiling, however, suggested minimal effects on amino acids. The results exemplify how detailed metabolic characterization of genetic proxies for drug targets can inform indications, pleiotropic effects, and pharmacological mechanisms. Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

NICU Network Neurobehavioral Profiles Predict Developmental Outcomes in a Low Risk Sample

PubMed Central

Sucharew, Heidi; Khoury, Jane C.; Xu, Yingying; Succop, Paul; Yolton, Kimberly

2012-01-01

Summary Latent profile analysis (LPA) has been used previously to classify neurobehavioral responses of infants prenatally exposed to cocaine and other drugs of abuse. The objective of this study was to define NICU Network Neurobehavioral Scale (NNNS) profile response patterns in a cohort of infants with no known cocaine exposure or other risks for neurobehavior deficits, and determine whether these profiles predict neurobehavioral outcomes in these low-risk infants. NNNS exams were performed on 355 low-risk infants at approximately 5 weeks after birth. LPA was used to define discrete profiles based on the standard NNNS summary scales. Associations between the infant profiles and neurobehavioral outcomes at one to three years of age were examined. Twelve of the 13 summary scales were used and three discrete NNNS profiles identified: social/easy going infants (44%), hypotonic infants (24%), and high arousal/difficult infants (32%). Statistically significant associations between NNNS profiles and later neurobehavioral outcomes were found for psychomotor development and externalizing behaviors. Hypotonic infants had both lower psychomotor development and lower externalizing scores compared to the other two profiles. In conclusion, three distinct profiles of the NNNS summary scores were identifiable using LPA among infants with no known cocaine exposure. These profile patterns were associated with early childhood neurobehavioral outcome, similar to findings reported in a study of infants with substantial cocaine exposure, demonstrating the utility of this profiling technique in both exposed and unexposed populations. PMID:22686386

User Profiles in Organizational Environments

ERIC Educational Resources Information Center

Teixeira, Claudio; Pinto, Joaquim Sousa; Martins, Joaquim Arnaldo

2008-01-01

Purpose: The aim of this paper is to describe a project to provide an online web portal that can be used as a front-end for all university users--students, teachers, staff--and services, library, administration, e-learning, and e-mail. Design/methodology/approach: The profile model proposed is mainly inheritable, defined by profile components with…

40 CFR 79.57 - Emission generation.

Code of Federal Regulations, 2010 CFR

2010-07-01

... recirculation, and feedback type. (4) Within the applicable subclass, the five highest selling vehicle/engine... emission generation vehicle/engine of the identical model, to ensure the availability of back-up emission... the filter in a sealed container, or the soluble organic fraction may be extracted and stored in a...

Macrolide drug interactions: an update.

PubMed

Pai, M P; Graci, D M; Amsden, G W

2000-04-01

To describe the current drug interaction profiles for the commonly used macrolides in the US and Europe, and to comment on the clinical impact of these interactions. A MEDLINE search (1975-1998) was performed to identify all pertinent studies, review articles, and case reports. When appropriate information was not available in the literature, data were obtained from the product manufacturers. All available data were reviewed to provide an unbiased account of possible drug interactions. Data for some of the interactions were not available from the literature, but were available from abstracts or company-supplied materials. Although the data were not always explicit, the best attempt was made to deliver pertinent information that clinical practitioners would need to formulate practice opinions. When more in-depth information was supplied in the form of a review or study report, a thorough explanation of pertinent methodology was supplied. Several clinically significant drug interactions have been identified since the approval of erythromycin. These interactions usually were related to the inhibition of the cytochrome P450 enzyme systems, which are responsible for the metabolism of many drugs. The decreased metabolism by the macrolides has in some instances resulted in potentially severe adverse events. The development and marketing of newer macrolides are hoped to improve the drug interaction profile associated with this class. However, this has produced variable success. Some of the newer macrolides demonstrated an interaction profile similar to that of erythromycin; others have improved profiles. The most success in avoiding drug interactions related to the inhibition of cytochrome P450 has been through the development of the azalide subclass, of which azithromycin is the first and only to be marketed. Azithromycin has not been demonstrated to inhibit the cytochrome P450 system in studies using a human liver microsome model, and to date has produced none of the classic drug interactions characteristic of the macrolides. Most of the available data regarding macrolide drug interactions are from studies in healthy volunteers and case reports. These data suggest that clarithromycin appears to have an interaction profile similar to that of erythromycin. Given this similarity, it is important to consider the interaction profile of clarithromycin when using erythromycin. This is especially necessary as funds for further studies of a medication available in generic form (e.g., erythromycin) are limited. Azithromycin has produced few clinically significant interactions with any agent cleared through the cytochrome P450 enzyme system. Although the available data are promising, the final test should come from studies conducted in patients who are taking potentially interacting compounds on a chronic basis.

Influence of in vivo growth on human glioma cell line gene expression: Convergent profiles under orthotopic conditions

PubMed Central

Camphausen, Kevin; Purow, Benjamin; Sproull, Mary; Scott, Tamalee; Ozawa, Tomoko; Deen, Dennis F.; Tofilon, Philip J.

2005-01-01

Defining the molecules that regulate tumor cell survival is an essential prerequisite for the development of targeted approaches to cancer treatment. Whereas many studies aimed at identifying such targets use human tumor cells grown in vitro or as s.c. xenografts, it is unclear whether such experimental models replicate the phenotype of the in situ tumor cell. To begin addressing this issue, we have used microarray analysis to define the gene expression profile of two human glioma cell lines (U251 and U87) when grown in vitro and in vivo as s.c. or as intracerebral (i.c.) xenografts. For each cell line, the gene expression profile generated from tissue culture was significantly different from that generated from the s.c. tumor, which was significantly different from those grown i.c. The disparity between the i.c gene expression profiles and those generated from s.c. xenografts suggests that whereas an in vivo growth environment modulates gene expression, orthotopic growth conditions induce a different set of modifications. In this study the U251 and U87 gene expression profiles generated under the three growth conditions were also compared. As expected, the profiles of the two glioma cell lines were significantly different when grown as monolayer cultures. However, the glioma cell lines had similar gene expression profiles when grown i.c. These results suggest that tumor cell gene expression, and thus phenotype, as defined in vitro is affected not only by in vivo growth but also by orthotopic growth, which may have implications regarding the identification of relevant targets for cancer therapy. PMID:15928080

Ethnic Differences in Lipid Profiles of Overweight, Obese, and Severely Obese Children and Adolescents 6-19 Years of Age.

PubMed

Dhuper, Sarita; Bayoumi, Nagla S; Shah, Yash D; Mehta, Shilpa

2017-06-01

Ethnic differences in lipid profiles exist in children and adolescents. This study assessed whether variations in lipid profiles present in overweight and obese youth were also observed in severely obese youth. Variations could explain the lower prevalence of the metabolic syndrome in certain ethnic groups at even severe levels of obesity. Data were obtained from the National Health and Nutrition Examination Survey for the years of 2001 through 2012. Subjects were divided into groups according to BMI classification. Normal weight was defined as a BMI less than the 85th percentile. Overweight was defined as a BMI between the 85th and 95th percentile. Class 1 obesity was defined as a BMI greater than the 95th percentile up to 120% of the 95th percentile. A BMI between 120% and 140% of the 95th percentile was defined as Class 2 obesity. Class 3 was defined as a BMI above 140% of the 95th percentile. Primary outcomes were mean total cholesterol, triglyceride, low-density lipoprotein, and high-density lipoprotein levels (HDL). The sample included 14,481 non-Hispanic black (NHB) (N = 4710), non-Hispanic white (N = 4910), and Mexican American (N = 4861) subjects. Across all BMI categories, the NHB group had significantly lower mean TG and higher mean HDL levels (p < 0.0001). Ethnic variations in lipid profiles were found in severely obese youth. These findings could explain the lower prevalence of the metabolic syndrome in NHB youth. Ethnic-specific guidelines are necessary for improved identification of those at risk at all levels of obesity.

Forensic trace DNA: a review

PubMed Central

2010-01-01

DNA analysis is frequently used to acquire information from biological material to aid enquiries associated with criminal offences, disaster victim identification and missing persons investigations. As the relevance and value of DNA profiling to forensic investigations has increased, so too has the desire to generate this information from smaller amounts of DNA. Trace DNA samples may be defined as any sample which falls below recommended thresholds at any stage of the analysis, from sample detection through to profile interpretation, and can not be defined by a precise picogram amount. Here we review aspects associated with the collection, DNA extraction, amplification, profiling and interpretation of trace DNA samples. Contamination and transfer issues are also briefly discussed within the context of trace DNA analysis. Whilst several methodological changes have facilitated profiling from trace samples in recent years it is also clear that many opportunities exist for further improvements. PMID:21122102

Gmz: a Gml Compression Model for Webgis

NASA Astrophysics Data System (ADS)

Khandelwal, A.; Rajan, K. S.

2017-09-01

Geography markup language (GML) is an XML specification for expressing geographical features. Defined by Open Geospatial Consortium (OGC), it is widely used for storage and transmission of maps over the Internet. XML schemas provide the convenience to define custom features profiles in GML for specific needs as seen in widely popular cityGML, simple features profile, coverage, etc. Simple features profile (SFP) is a simpler subset of GML profile with support for point, line and polygon geometries. SFP has been constructed to make sure it covers most commonly used GML geometries. Web Feature Service (WFS) serves query results in SFP by default. But it falls short of being an ideal choice due to its high verbosity and size-heavy nature, which provides immense scope for compression. GMZ is a lossless compression model developed to work for SFP compliant GML files. Our experiments indicate GMZ achieves reasonably good compression ratios and can be useful in WebGIS based applications.

Biotechnology and genetic engineering in the new drug development. Part III. Biocatalysis, metabolic engineering and molecular modelling.

PubMed

Stryjewska, Agnieszka; Kiepura, Katarzyna; Librowski, Tadeusz; Lochyński, Stanisław

2013-01-01

Industrial biotechnology has been defined as the use and application of biotechnology for the sustainable processing and production of chemicals, materials and fuels. It makes use of biocatalysts such as microbial communities, whole-cell microorganisms or purified enzymes. In the review these processes are described. Drug design is an iterative process which begins when a chemist identifies a compound that displays an interesting biological profile and ends when both the activity profile and the chemical synthesis of the new chemical entity are optimized. Traditional approaches to drug discovery rely on a stepwise synthesis and screening program for large numbers of compounds to optimize activity profiles. Over the past ten to twenty years, scientists have used computer models of new chemical entities to help define activity profiles, geometries and relativities. This article introduces inter alia the concepts of molecular modelling and contains references for further reading.