Motifs, modules and games in bacteria.

PubMed

Wolf, Denise M; Arkin, Adam P

2003-04-01

Global explorations of regulatory network dynamics, organization and evolution have become tractable thanks to high-throughput sequencing and molecular measurement of bacterial physiology. From these, a nascent conceptual framework is developing, that views the principles of regulation in term of motifs, modules and games. Motifs are small, repeated, and conserved biological units ranging from molecular domains to small reaction networks. They are arranged into functional modules, genetically dissectible cellular functions such as the cell cycle, or different stress responses. The dynamical functioning of modules defines the organism's strategy to survive in a game, pitting cell against cell, and cell against environment. Placing pathway structure and dynamics into an evolutionary context begins to allow discrimination between those physical and molecular features that particularize a species to its surroundings, and those that provide core physiological function. This approach promises to generate a higher level understanding of cellular design, pathway evolution and cellular bioengineering.

Motifs, modules and games in bacteria

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

Wolf, Denise M.; Arkin, Adam P.

2003-04-01

Global explorations of regulatory network dynamics, organization and evolution have become tractable thanks to high-throughput sequencing and molecular measurement of bacterial physiology. From these, a nascent conceptual framework is developing, that views the principles of regulation in term of motifs, modules and games. Motifs are small, repeated, and conserved biological units ranging from molecular domains to small reaction networks. They are arranged into functional modules, genetically dissectible cellular functions such as the cell cycle, or different stress responses. The dynamical functioning of modules defines the organism's strategy to survive in a game, pitting cell against cell, and cell against environment.more » Placing pathway structure and dynamics into an evolutionary context begins to allow discrimination between those physical and molecular features that particularize a species to its surroundings, and those that provide core physiological function. This approach promises to generate a higher level understanding of cellular design, pathway evolution and cellular bioengineering.« less

Contribution of different taste cells and signaling pathways to the discrimination of "bitter" taste stimuli by an insect.

PubMed

Glendinning, John I; Davis, Adrienne; Ramaswamy, Sudha

2002-08-15

Animals can discriminate among many different types of foods. This discrimination process involves multiple sensory systems, but the sense of taste is known to play a central role. We asked how the taste system contributes to the discrimination of different "bitter" taste stimuli in Manduca sexta caterpillars. This insect has approximately eight bilateral pairs of taste cells that respond selectively to bitter taste stimuli. Each bilateral pair of bitter-sensitive taste cells has a different molecular receptive range (MRR); some of these taste cells also contain two signaling pathways with distinctive MRRs and temporal patterns of spiking. To test for discrimination, we habituated the caterpillar's taste-mediated aversive response to one bitter taste stimulus (salicin) and then asked whether this habituation phenomenon generalized to four other bitter taste stimuli (caffeine, aristolochic acid, Grindelia extract, and Canna extract). We inferred that the two compounds were discriminable if the habituation phenomenon failed to generalize (e.g., from salicin to aristolochic acid). We found that M. sexta could discriminate between salicin and those bitter taste stimuli that activate (1) different populations of bitter-sensitive taste cells (Grindelia extract and Canna extract) or (2) different signaling pathways within the same bitter-sensitive taste cell (aristolochic acid). M. sexta could not discriminate between salicin and a bitter taste stimulus that activates the same signaling pathway within the same bitter-sensitive taste cell (caffeine). We propose that the heterogeneous population of bitter-sensitive taste cells and signaling pathways within this insect facilitates the discrimination of bitter taste stimuli.

Calcium Imaging of Basal Forebrain Activity during Innate and Learned Behaviors

PubMed Central

Harrison, Thomas C.; Pinto, Lucas; Brock, Julien R.; Dan, Yang

2016-01-01

The basal forebrain (BF) plays crucial roles in arousal, attention, and memory, and its impairment is associated with a variety of cognitive deficits. The BF consists of cholinergic, GABAergic, and glutamatergic neurons. Electrical or optogenetic stimulation of BF cholinergic neurons enhances cortical processing and behavioral performance, but the natural activity of these cells during behavior is only beginning to be characterized. Even less is known about GABAergic and glutamatergic neurons. Here, we performed microendoscopic calcium imaging of BF neurons as mice engaged in spontaneous behaviors in their home cages (innate) or performed a go/no-go auditory discrimination task (learned). Cholinergic neurons were consistently excited during movement, including running and licking, but GABAergic and glutamatergic neurons exhibited diverse responses. All cell types were activated by overt punishment, either inside or outside of the discrimination task. These findings reveal functional similarities and distinctions between BF cell types during both spontaneous and task-related behaviors. PMID:27242444

Two models for evaluating landslide hazards

USGS Publications Warehouse

Davis, J.C.; Chung, C.-J.; Ohlmacher, G.C.

2006-01-01

Two alternative procedures for estimating landslide hazards were evaluated using data on topographic digital elevation models (DEMs) and bedrock lithologies in an area adjacent to the Missouri River in Atchison County, Kansas, USA. The two procedures are based on the likelihood ratio model but utilize different assumptions. The empirical likelihood ratio model is based on non-parametric empirical univariate frequency distribution functions under an assumption of conditional independence while the multivariate logistic discriminant model assumes that likelihood ratios can be expressed in terms of logistic functions. The relative hazards of occurrence of landslides were estimated by an empirical likelihood ratio model and by multivariate logistic discriminant analysis. Predictor variables consisted of grids containing topographic elevations, slope angles, and slope aspects calculated from a 30-m DEM. An integer grid of coded bedrock lithologies taken from digitized geologic maps was also used as a predictor variable. Both statistical models yield relative estimates in the form of the proportion of total map area predicted to already contain or to be the site of future landslides. The stabilities of estimates were checked by cross-validation of results from random subsamples, using each of the two procedures. Cell-by-cell comparisons of hazard maps made by the two models show that the two sets of estimates are virtually identical. This suggests that the empirical likelihood ratio and the logistic discriminant analysis models are robust with respect to the conditional independent assumption and the logistic function assumption, respectively, and that either model can be used successfully to evaluate landslide hazards. ?? 2006.

Identification of two immortalized cell lines, ECV304 and bEnd3, for in vitro permeability studies of blood-brain barrier

PubMed Central

Mei, Shenghui; Jin, Hong; Zhu, Bin; Tian, Yue; Huo, Jiping; Cui, Xu; Guo, Anchen; Zhao, Zhigang

2017-01-01

To identify suitable cell lines for a mimetic system of in vivo blood-brain barrier (BBB) for drug permeability assessment, we characterized two immortalized cell lines, ECV304 and bEnd3 in the respect of the tightness, tight junction proteins, P-glycoprotein (P-gp) function and discriminative brain penetration. The ECV304 monoculture achieved higher transendothelial electrical resistance (TEER) and lower permeability to Lucifer yellow than bEnd3. However, co-culture with rat glioma C6 cells impaired the integrity of ECV304 and bEnd3 cell layers perhaps due to the heterogeneity among C6 cells in inducing BBB characteristics. The immunostaining of ZO-1 delivered distinct bands along cell borders on both cell lines while those of occludin and claudin-5 were diffused and weak. P-gp functionality was only proved in bEnd3 by Rhodamine 123 (R123) uptake assay. A permeability test of reference compounds displayed a similar rank order (digoxin < R123 < quinidine, verapamil < propranolol) in ECV304 and bEnd3 cells. In comparison with bEnd3, ECV304 developed tighter barrier for the passage of reference compounds and higher discrimination between transcellular and paracellular transport. However, the monoculture models of ECV304 and bEnd3 fail to achieve the sufficient tightness of in vitro BBB permeability models with high TEER and evident immunostaining of tight junction proteins. Further strategies to enhance the paracellular tightness of both cell lines to mimic in vivo BBB tight barrier deserve to be conducted. PMID:29059256

Identification of two immortalized cell lines, ECV304 and bEnd3, for in vitro permeability studies of blood-brain barrier.

PubMed

Yang, Shu; Mei, Shenghui; Jin, Hong; Zhu, Bin; Tian, Yue; Huo, Jiping; Cui, Xu; Guo, Anchen; Zhao, Zhigang

2017-01-01

To identify suitable cell lines for a mimetic system of in vivo blood-brain barrier (BBB) for drug permeability assessment, we characterized two immortalized cell lines, ECV304 and bEnd3 in the respect of the tightness, tight junction proteins, P-glycoprotein (P-gp) function and discriminative brain penetration. The ECV304 monoculture achieved higher transendothelial electrical resistance (TEER) and lower permeability to Lucifer yellow than bEnd3. However, co-culture with rat glioma C6 cells impaired the integrity of ECV304 and bEnd3 cell layers perhaps due to the heterogeneity among C6 cells in inducing BBB characteristics. The immunostaining of ZO-1 delivered distinct bands along cell borders on both cell lines while those of occludin and claudin-5 were diffused and weak. P-gp functionality was only proved in bEnd3 by Rhodamine 123 (R123) uptake assay. A permeability test of reference compounds displayed a similar rank order (digoxin < R123 < quinidine, verapamil < propranolol) in ECV304 and bEnd3 cells. In comparison with bEnd3, ECV304 developed tighter barrier for the passage of reference compounds and higher discrimination between transcellular and paracellular transport. However, the monoculture models of ECV304 and bEnd3 fail to achieve the sufficient tightness of in vitro BBB permeability models with high TEER and evident immunostaining of tight junction proteins. Further strategies to enhance the paracellular tightness of both cell lines to mimic in vivo BBB tight barrier deserve to be conducted.

Robust and Accurate Discrimination of Self/Non-Self Antigen Presentations by Regulatory T Cell Suppression.

PubMed

Furusawa, Chikara; Yamaguchi, Tomoyuki

The immune response by T cells usually discriminates self and non-self antigens, even though the negative selection of self-reactive T cells is imperfect and a certain fraction of T cells can respond to self-antigens. In this study, we construct a simple mathematical model of T cell populations to analyze how such self/non-self discrimination is possible. The results demonstrate that the control of the immune response by regulatory T cells enables a robust and accurate discrimination of self and non-self antigens, even when there is a significant overlap between the affinity distribution of T cells to self and non-self antigens. Here, the number of regulatory T cells in the system acts as a global variable controlling the T cell population dynamics. The present study provides a basis for the development of a quantitative theory for self and non-self discrimination in the immune system and a possible strategy for its experimental verification.

Robust and Accurate Discrimination of Self/Non-Self Antigen Presentations by Regulatory T Cell Suppression

PubMed Central

Furusawa, Chikara; Yamaguchi, Tomoyuki

2016-01-01

The immune response by T cells usually discriminates self and non-self antigens, even though the negative selection of self-reactive T cells is imperfect and a certain fraction of T cells can respond to self-antigens. In this study, we construct a simple mathematical model of T cell populations to analyze how such self/non-self discrimination is possible. The results demonstrate that the control of the immune response by regulatory T cells enables a robust and accurate discrimination of self and non-self antigens, even when there is a significant overlap between the affinity distribution of T cells to self and non-self antigens. Here, the number of regulatory T cells in the system acts as a global variable controlling the T cell population dynamics. The present study provides a basis for the development of a quantitative theory for self and non-self discrimination in the immune system and a possible strategy for its experimental verification. PMID:27668873

Neuron analysis of visual perception

NASA Technical Reports Server (NTRS)

Chow, K. L.

1980-01-01

The receptive fields of single cells in the visual system of cat and squirrel monkey were studied investigating the vestibular input affecting the cells, and the cell's responses during visual discrimination learning process. The receptive field characteristics of the rabbit visual system, its normal development, its abnormal development following visual deprivation, and on the structural and functional re-organization of the visual system following neo-natal and prenatal surgery were also studied. The results of each individual part of each investigation are detailed.

Photoreceptor Cells With Profound Structural Deficits Can Support Useful Vision in Mice

PubMed Central

Thompson, Stewart; Blodi, Frederick R.; Lee, Swan; Welder, Chris R.; Mullins, Robert F.; Tucker, Budd A.; Stasheff, Steven F.; Stone, Edwin M.

2014-01-01

Purpose. In animal models of degenerative photoreceptor disease, there has been some success in restoring photoreception by transplanting stem cell–derived photoreceptor cells into the subretinal space. However, only a small proportion of transplanted cells develop extended outer segments, considered critical for photoreceptor cell function. The purpose of this study was to determine whether photoreceptor cells that lack a fully formed outer segment could usefully contribute to vision. Methods. Retinal and visual function was tested in wild-type and Rds mice at 90 days of age (RdsP90). Photoreceptor cells of mice homozygous for the Rds mutation in peripherin 2 never develop a fully formed outer segment. The electroretinogram and multielectrode recording of retinal ganglion cells were used to test retinal responses to light. Three distinct visual behaviors were used to assess visual capabilities: the optokinetic tracking response, the discrimination-based visual water task, and a measure of the effect of vision on wheel running. Results. RdsP90 mice had reduced but measurable electroretinogram responses to light, and exhibited light-evoked responses in multiple types of retinal ganglion cells, the output neurons of the retina. In optokinetic and discrimination-based tests, acuity was measurable but reduced, most notably when contrast was decreased. The wheel running test showed that RdsP90 mice needed 3 log units brighter luminance than wild type to support useful vision (10 cd/m2). Conclusions. Photoreceptors that lack fully formed outer segments can support useful vision. This challenges the idea that normal cellular structure needs to be completely reproduced for transplanted cells to contribute to useful vision. PMID:24569582

Cell-cell recognition and social networking in bacteria

PubMed Central

Troselj, Vera; Cao, Pengbo; Wall, Daniel

2018-01-01

SUMMARY The ability to recognize self and to recognize partnering cells allows microorganisms to build social networks that perform functions beyond the capabilities of the individual. In bacteria, recognition typically involves genetic determinants that provide cell surface receptors or diffusible signaling chemicals to identify proximal cells at the molecular level that can participate in cooperative processes. Social networks also rely on discriminating mechanisms to exclude competing cells from joining and exploiting their groups. In addition to their appropriate genotypes, cell-cell recognition also requires compatible phenotypes, which vary according to environmental cues or exposures as well as stochastic processes that leads to heterogeneity and potential disharmony in the population. Understanding how bacteria identify their social partners and how they synchronize their behaviors to conduct multicellular functions is an expanding field of research. Here we review recent progress in the field and contrast the various strategies used in recognition and behavioral networking. PMID:29194914

Evaluation of the udder health status in subclinical mastitis affected dairy cows through bacteriological culture, somatic cell count and thermographic imaging.

PubMed

Bortolami, A; Fiore, E; Gianesella, M; Corrò, M; Catania, S; Morgante, M

2015-01-01

Subclinical mastitis in dairy cows is a big economic loss for farmers. The monitoring of subclinical mastitis is usually performed through Somatic Cell Count (SCC) in farm but there is the need of new diagnostic systems able to quickly identify cows affected by subclinical infections of the udder. The aim of this study was to evaluate the potential application of thermographic imaging compared to SCC and bacteriological culture for infection detection in cow affected by subclinical mastitis and possibly to discriminate between different pathogens. In this study we evaluated the udder health status of 98 Holstein Friesian dairy cows with high SCC in 4 farms. From each cow a sample of milk was collected from all the functional quarters and submitted to bacteriological culture, SCC and Mycoplasma spp. culture. A thermographic image was taken from each functional udder quarter and nipple. Pearson's correlations and Analysis of Variance were performed in order to evaluate the different diagnostic techniques. The most frequent pathogen isolated was Staphylococcus aureus followed by Coagulase Negative Staphylococci (CNS), Streptococcus uberis, Streptococcus agalactiae and others. The Somatic Cell Score (SCS) was able to discriminate (p<0.05) cows positive for a pathogen from cows negative at the bacteriological culture except for cows with infection caused by CNS. Infrared thermography was correlated to SCS (p<0.05) but was not able to discriminate between positive and negative cows. Thermographic imaging seems to be promising in evaluating the inflammation status of cows affected by subclinical mastitis but seems to have a poor diagnostic value.

Detection of single-copy functional genes in prokaryotic cells by two-pass TSA-FISH with polynucleotide probes.

PubMed

Kawakami, Shuji; Hasegawa, Takuya; Imachi, Hiroyuki; Yamaguchi, Takashi; Harada, Hideki; Ohashi, Akiyoshi; Kubota, Kengo

2012-02-01

In situ detection of functional genes with single-cell resolution is currently of interest to microbiologists. Here, we developed a two-pass tyramide signal amplification (TSA)-fluorescence in situ hybridization (FISH) protocol with PCR-derived polynucleotide probes for the detection of single-copy genes in prokaryotic cells. The mcrA gene and the apsA gene in methanogens and sulfate-reducing bacteria, respectively, were targeted. The protocol showed bright fluorescence with a good signal-to-noise ratio and achieved a high efficiency of detection (>98%). The discrimination threshold was approximately 82-89% sequence identity. Microorganisms possessing the mcrA or apsA gene in anaerobic sludge samples were successfully detected by two-pass TSA-FISH with polynucleotide probes. The developed protocol is useful for identifying single microbial cells based on functional gene sequences. Copyright © 2011 Elsevier B.V. All rights reserved.

Fetal alcohol exposure leads to abnormal olfactory bulb development and impaired odor discrimination in adult mice.

PubMed

Akers, Katherine G; Kushner, Steven A; Leslie, Ana T; Clarke, Laura; van der Kooy, Derek; Lerch, Jason P; Frankland, Paul W

2011-07-07

Children whose mothers consumed alcohol during pregnancy exhibit widespread brain abnormalities and a complex array of behavioral disturbances. Here, we used a mouse model of fetal alcohol exposure to investigate relationships between brain abnormalities and specific behavioral alterations during adulthood. Mice drank a 10% ethanol solution throughout pregnancy. When fetal alcohol-exposed offspring reached adulthood, we used high resolution MRI to conduct a brain-wide screen for structural changes and found that the largest reduction in volume occurred in the olfactory bulbs. Next, we tested adult mice in an associative olfactory task and found that fetal alcohol exposure impaired discrimination between similar odors but left odor memory intact. Finally, we investigated olfactory bulb neurogenesis as a potential mechanism by performing an in vitro neurosphere assay, in vivo labeling of new cells using BrdU, and in vivo labeling of new cells using a transgenic reporter system. We found that fetal alcohol exposure decreased the number of neural precursor cells in the subependymal zone and the number of new cells in the olfactory bulbs during the first few postnatal weeks. Using a combination of techniques, including structural brain imaging, in vitro and in vivo cell detection methods, and behavioral testing, we found that fetal alcohol exposure results in smaller olfactory bulbs and impairments in odor discrimination that persist into adulthood. Furthermore, we found that these abnormalities in olfactory bulb structure and function may arise from deficits in the generation of new olfactory bulb neurons during early postnatal development.

Crimpy enables discrimination of presynaptic and postsynaptic pools of a BMP at the Drosophila neuromuscular junction.

PubMed

James, Rebecca E; Hoover, Kendall M; Bulgari, Dinara; McLaughlin, Colleen N; Wilson, Christopher G; Wharton, Kristi A; Levitan, Edwin S; Broihier, Heather T

2014-12-08

Distinct pools of the bone morphogenetic protein (BMP) Glass bottom boat (Gbb) control structure and function of the Drosophila neuromuscular junction. Specifically, motoneuron-derived Gbb regulates baseline neurotransmitter release, whereas muscle-derived Gbb regulates neuromuscular junction growth. Yet how cells differentiate between these ligand pools is not known. Here we present evidence that the neuronal Gbb-binding protein Crimpy (Cmpy) permits discrimination of pre- and postsynaptic ligand by serving sequential functions in Gbb signaling. Cmpy first delivers Gbb to dense core vesicles (DCVs) for activity-dependent release from presynaptic terminals. In the absence of Cmpy, Gbb is no longer associated with DCVs and is not released by activity. Electrophysiological analyses demonstrate that Cmpy promotes Gbb's proneurotransmission function. Surprisingly, the Cmpy ectodomain is itself released upon DCV exocytosis, arguing that Cmpy serves a second function in BMP signaling. In addition to trafficking Gbb to DCVs, we propose that Gbb/Cmpy corelease from presynaptic terminals defines a neuronal protransmission signal. Copyright © 2014 Elsevier Inc. All rights reserved.

Crimpy enables discrimination of pre and postsynaptic pools of a BMP at the Drosophila NMJ

PubMed Central

James, Rebecca E.; Hoover, Kendall M.; Bulgari, Dinara; McLaughlin, Colleen N.; Wilson, Christopher G.; Wharton, Kristi A.; Levitan, Edwin S.; Broihier, Heather T.

2014-01-01

Summary Distinct pools of the BMP Glass bottom boat (Gbb) control structure and function of the Drosophila neuromuscular junction. Specifically, motoneuron-derived Gbb regulates baseline neurotransmitter release, while muscle-derived Gbb regulates NMJ growth. Yet how cells differentiate between these ligand pools is not known. Here we present evidence that the neuronal Gbb-binding protein Crimpy (Cmpy) permits discrimination of pre and postsynaptic ligand by serving sequential functions in Gbb signaling. Cmpy first delivers Gbb to dense core vesicles (DCVs) for activity-dependent release from presynaptic terminals. In the absence of Cmpy, Gbb is no longer associated with DCVs and is not released by activity. Electrophysiological analyses demonstrate that Cmpy promotes Gbb's pro-neurotransmission function. Surprisingly, the Cmpy ectodomain is itself released upon DCV exocytosis, arguing that Cmpy serves a second function in BMP signaling. In addition to trafficking Gbb to DCVs, we propose that Gbb/Cmpy co-release from presynaptic terminals defines a neuronal pro-transmission signal. PMID:25453556

Tropomyosins as discriminators of myosin function.

PubMed

Ostap, E Michael

2008-01-01

Vertebrate nonmuscle cells express multiple tropomyosin isoforms that are sorted to subcellular compartments that have distinct morphological and dynamic properties. The creation of these compartments has a role in controlling cell morphology, cell migration and polarization of cellular components. There is increasing evidence that nonmuscle myosins are regulated by tropomyosin in these compartments via the regulation of actin attachment, ATPase kinetics, or by stabilization of cytoskeletal tracks for myosin-based transport. In this chapter, I review the literature describing the regulation of various myosins by tropomyosins and consider the mechanisms for this regulation.

Discriminative Ability of Plasma Branched-Chain Amino Acid Levels for Glucose Intolerance in Families At Risk for Type 2 Diabetes.

PubMed

Jainandunsing, Sjaam; Wattimena, J L Darcos; Verhoeven, Adrie J M; Langendonk, Janneke G; Rietveld, Trinet; Isaacs, Aaron J; Sijbrands, Eric J G; de Rooij, Felix W M

2016-04-01

Insulin resistance and glucose intolerance have been associated with increased plasma levels of branched-chain amino acids (BCAA). BCAA levels do not predict T2DM in the population. We determined the discriminative ability of fasting BCAA levels for glucose intolerance in nondiabetic relatives of patients with T2DM of two different ethnicities. Based on oral glucose tolerance test (OGTT), first-degree relatives of patients with T2DM were categorized as normal glucose tolerance, prediabetes, or T2DM. Included were 34, 12, and 18 Caucasian and 22, 12, and 23 Asian Indian participants, respectively. BCAA levels were measured in fasting plasma together with alanine, phenylalanine, and tyrosine. Insulin sensitivity and beta-cell function were assessed by indices derived from an extended OGTT and their relationship with plasma BCAA levels was assessed in multivariate regression analysis. The value of the amino acids for discriminating prediabetes among nondiabetic family members was determined with the area under the curve of receiver-operated characteristics (c-index). BCAA levels were higher in diabetic than in normoglycemic family members in the Caucasians (P = 0.001) but not in the Asian Indians. In both groups, BCAA levels were associated with waist-hip ratio (β = 0.31; P = 0.03 and β = 0.42; P = 0.001, respectively) but not with indices of insulin sensitivity or beta-cell function. The c-index of BCAA for discriminating prediabetes among nondiabetic participants was 0.83 and 0.74 in Caucasians and Asian Indians, respectively, which increased to 0.84 and 0.79 by also including the other amino acids. The c-index of fasting glucose for discriminating prediabetes increased from 0.91 to 0.92 in Caucasians and 0.85 to 0.97 (P = 0.04) in Asian Indians by inclusion of BCAA+alanine, phenylalanine, and tyrosine. Adding fasting plasma BCAA levels, combined with phenylalanine, tyrosine and alanine to fasting glucose improved discriminative ability for the prediabetic state within Asian Indian families at risk for T2DM. BCAA levels may serve as biomarkers for early development of glucose intolerance in these families.

Theoretical aspects of color vision

NASA Technical Reports Server (NTRS)

Wolbarsht, M. L.

1972-01-01

The three color receptors of Young-Helmholtz and the opponent colors type of information processing postulated by Hering are both present in the human visual system. This mixture accounts for both the phenomena of color matching or hue discrimination and such perceptual qualities of color as the division of the spectrum into color bands. The functioning of the cells in the visual system, especially within the retina, and the relation of this function to color perception are discussed.

Immunohistochemical detection of active transforming growth factor-beta in situ using engineered tissue

NASA Technical Reports Server (NTRS)

Barcellos-Hoff, M. H.; Ehrhart, E. J.; Kalia, M.; Jirtle, R.; Flanders, K.; Tsang, M. L.; Chatterjee, A. (Principal Investigator)

1995-01-01

The biological activity of transforming growth factor-beta 1 (TGF-beta) is governed by dissociation from its latent complex. Immunohistochemical discrimination of active and latent TGF-beta could provide insight into TGF-beta activation in physiological and pathological processes. However, evaluation of immunoreactivity specificity in situ has been hindered by the lack of tissue in which TGF-beta status is known. To provide in situ analysis of antibodies to differentiate between these functional forms, we used xenografts of human tumor cells modified by transfection to overexpress latent TGF-beta or constitutively active TGF-beta. This comparison revealed that, whereas most antibodies did not differentiate between TGF-beta activation status, the immunoreactivity of some antibodies was activation dependent. Two widely used peptide antibodies to the amino-terminus of TGF-beta, LC(1-30) and CC(1-30) showed marked preferential immunoreactivity with active TGF-beta versus latent TGF-beta in cryosections. However, in formalin-fixed, paraffin-embedded tissue, discrimination of active TGF-beta by CC(1-30) was lost and immunoreactivity was distinctly extracellular, as previously reported for this antibody. Similar processing-dependent extracellular localization was found with a neutralizing antibody raised to recombinant TGF-beta. Antigen retrieval recovered cell-associated immunoreactivity of both antibodies. Two antibodies to peptides 78-109 showed mild to moderate preferential immunoreactivity with active TGF-beta only in paraffin sections. LC(1-30) was the only antibody tested that discriminated active from latent TGF-beta in both frozen and paraffin-embedded tissue. Thus, in situ discrimination of active versus latent TGF-beta depends on both the antibody and tissue preparation. We propose that tissues engineered to express a specific form of a given protein provide a physiological setting in which to evaluate antibody reactivity with specific functional forms of a protein.

A tissue microarray study of toll-like receptor 4, decoy receptor 3, and external signal regulated kinase 1/2 expressions in astrocytoma.

PubMed

Lin, Chih-Kung; Ting, Chun-Chieh; Tsai, Wen-Chiuan; Chen, Yuan-Wu; Hueng, Dueng-Yuan

2016-01-01

Decoy receptor 3 (DcR3) functions as a death decoy inhibiting apoptosis mediated by the tumor necrosis factor receptor family. It is highly expressed in many tumors and its expression can be regulated by the MAPK/ERK signaling pathway and ERK is a vital member of this pathway. Toll-like receptor 4 (TLR4) is expressed on immune cells. Increased TLR4 expression has been associated with various types of cancers. The study was conducted to investigate the expression of DcR3, ERK1/2, and TLR4 in astrocytomas and evaluate if they are validating markers for discriminating glioblastoma from anaplastic astrocytoma in limited surgical specimen. Expression of DcR3, ERK1/2, and TLR4 was determined by immunohistochemical staining of tissue microarray from 48 paraffin-embedded tissues. A binary logistic regression method was used to generate functions that discriminate between anaplastic astrocytomas and glioblastomas. The expression of TLR4 and DcR3 was significantly higher in glioblastomas than in anaplastic astrocytomas. DcR3 could discriminate anaplastic astrocytomas from glioblastomas with high sensitivity (93.8%), specificity (90%), and accuracy (92.3%). Our results suggest that DcR3 may be a useful marker for discriminating anaplastic astrocytomas from glioblastomas.

The Case for Absolute Ligand Discrimination: Modeling Information Processing and Decision by Immune T Cells

NASA Astrophysics Data System (ADS)

François, Paul; Altan-Bonnet, Grégoire

2016-03-01

Some cells have to take decision based on the quality of surroundings ligands, almost irrespective of their quantity, a problem we name "absolute discrimination". An example of absolute discrimination is recognition of not-self by immune T Cells. We show how the problem of absolute discrimination can be solved by a process called "adaptive sorting". We review several implementations of adaptive sorting, as well as its generic properties such as antagonism. We show how kinetic proofreading with negative feedback implement an approximate version of adaptive sorting in the immune context. Finally, we revisit the decision problem at the cell population level, showing how phenotypic variability and feedbacks between population and single cells are crucial for proper decision.

Trauma exposure, discrimination, and romantic relationship functioning: A longitudinal investigation among LGB young adults

PubMed Central

Sullivan, Timothy J.; Feinstein, Brian A.; Marshall, Amy D.; Mustanski, Brian

2017-01-01

Sexual orientation-related discrimination is common among sexual minority individuals, but its influence on romantic relationship functioning remains unclear. Further, exposure to potentially traumatic events may influence the association between discrimination and relationship functioning, but this has not been tested among sexual minority couples to date. The current study examines breadth of lifetime trauma exposure as a moderator of the associations between recent discrimination and changes in relationship functioning (satisfaction, commitment, and trust) over twelve months among 86 racially/ethnically diverse sexual minority young adults in relationships. For those with low trauma exposure, discrimination was associated with increases in satisfaction and commitment, but not trust. In contrast, for those with high trauma exposure, discrimination was not associated with changes in relationship functioning. Thus, some partnered sexual minority young adults may experience resilience in the face of discrimination, such that discrimination may promote positive relationship functioning. However, this does not appear to extend to those with more extensive trauma exposure histories. With an eye toward informing interventions, these findings call for additional research on individual differences in responses to discrimination, such as support seeking and dyadic coping. PMID:29527540

Different thresholds for detection and discrimination of odors in the honey bee (Apis mellifera).

PubMed

Wright, Geraldine A; Smith, Brian H

2004-02-01

Naturally occurring odors used by animals for mate recognition, food identification and other purposes must be detected at concentrations that vary across several orders of magnitude. Olfactory systems must therefore have the capacity to represent odors over a large range of concentrations regardless of dramatic changes in the salience, or perceived intensity, of a stimulus. The stability of the representation of an odor relative to other odors across concentration has not been extensively evaluated. We tested the ability of honey bees to discriminate pure odorants across a range of concentrations at and above their detection threshold. Our study showed that pure odorant compounds became progressively easier for honey bees to discriminate with increasing concentration. Discrimination is, therefore, a function of odorant concentration. We hypothesize that the recruitment of sensory cell populations across a range of concentrations may be important for odor coding, perhaps by changing its perceptual qualities or by increasing its salience against background stimuli, and that this mechanism is a general property of olfactory systems.

iPHLoc-ES: Identification of bacteriophage protein locations using evolutionary and structural features.

PubMed

Shatabda, Swakkhar; Saha, Sanjay; Sharma, Alok; Dehzangi, Abdollah

2017-12-21

Bacteriophage proteins are viruses that can significantly impact on the functioning of bacteria and can be used in phage based therapy. The functioning of Bacteriophage in the host bacteria depends on its location in those host cells. It is very important to know the subcellular location of the phage proteins in a host cell in order to understand their working mechanism. In this paper, we propose iPHLoc-ES, a prediction method for subcellular localization of bacteriophage proteins. We aim to solve two problems: discriminating between host located and non-host located phage proteins and discriminating between the locations of host located protein in a host cell (membrane or cytoplasm). To do this, we extract sets of evolutionary and structural features of phage protein and employ Support Vector Machine (SVM) as our classifier. We also use recursive feature elimination (RFE) to reduce the number of features for effective prediction. On standard dataset using standard evaluation criteria, our method significantly outperforms the state-of-the-art predictor. iPHLoc-ES is readily available to use as a standalone tool from: https://github.com/swakkhar/iPHLoc-ES/ and as a web application from: http://brl.uiu.ac.bd/iPHLoc-ES/. Copyright © 2017 Elsevier Ltd. All rights reserved.

Different TCR-induced T lymphocyte responses are potentiated by stiffness with variable sensitivity

PubMed Central

Saitakis, Michael; Dogniaux, Stéphanie; Goudot, Christel; Bufi, Nathalie; Asnacios, Sophie; Maurin, Mathieu; Randriamampita, Clotilde; Asnacios, Atef; Hivroz, Claire

2017-01-01

T cells are mechanosensitive but the effect of stiffness on their functions is still debated. We characterize herein how human primary CD4+ T cell functions are affected by stiffness within the physiological Young’s modulus range of 0.5 kPa to 100 kPa. Stiffness modulates T lymphocyte migration and morphological changes induced by TCR/CD3 triggering. Stiffness also increases TCR-induced immune system, metabolism and cell-cycle-related genes. Yet, upon TCR/CD3 stimulation, while cytokine production increases within a wide range of stiffness, from hundreds of Pa to hundreds of kPa, T cell metabolic properties and cell cycle progression are only increased by the highest stiffness tested (100 kPa). Finally, mechanical properties of adherent antigen-presenting cells modulate cytokine production by T cells. Together, these results reveal that T cells discriminate between the wide range of stiffness values found in the body and adapt their responses accordingly. DOI: http://dx.doi.org/10.7554/eLife.23190.001 PMID:28594327

Assay based on electrical impedance spectroscopy to discriminate between normal and cancerous mammalian cells

NASA Astrophysics Data System (ADS)

Giana, Fabián Eduardo; Bonetto, Fabián José; Bellotti, Mariela Inés

2018-03-01

In this work we present an assay to discriminate between normal and cancerous cells. The method is based on the measurement of electrical impedance spectra of in vitro cell cultures. We developed a protocol consisting on four consecutive measurement phases, each of them designed to obtain different information about the cell cultures. Through the analysis of the measured data, 26 characteristic features were obtained for both cell types. From the complete set of features, we selected the most relevant in terms of their discriminant capacity by means of conventional statistical tests. A linear discriminant analysis was then carried out on the selected features, allowing the classification of the samples in normal or cancerous with 4.5% of false positives and no false negatives.

Assay based on electrical impedance spectroscopy to discriminate between normal and cancerous mammalian cells.

PubMed

Giana, Fabián Eduardo; Bonetto, Fabián José; Bellotti, Mariela Inés

2018-03-01

In this work we present an assay to discriminate between normal and cancerous cells. The method is based on the measurement of electrical impedance spectra of in vitro cell cultures. We developed a protocol consisting on four consecutive measurement phases, each of them designed to obtain different information about the cell cultures. Through the analysis of the measured data, 26 characteristic features were obtained for both cell types. From the complete set of features, we selected the most relevant in terms of their discriminant capacity by means of conventional statistical tests. A linear discriminant analysis was then carried out on the selected features, allowing the classification of the samples in normal or cancerous with 4.5% of false positives and no false negatives.

Fetal alcohol exposure leads to abnormal olfactory bulb development and impaired odor discrimination in adult mice

PubMed Central

2011-01-01

Background Children whose mothers consumed alcohol during pregnancy exhibit widespread brain abnormalities and a complex array of behavioral disturbances. Here, we used a mouse model of fetal alcohol exposure to investigate relationships between brain abnormalities and specific behavioral alterations during adulthood. Results Mice drank a 10% ethanol solution throughout pregnancy. When fetal alcohol-exposed offspring reached adulthood, we used high resolution MRI to conduct a brain-wide screen for structural changes and found that the largest reduction in volume occurred in the olfactory bulbs. Next, we tested adult mice in an associative olfactory task and found that fetal alcohol exposure impaired discrimination between similar odors but left odor memory intact. Finally, we investigated olfactory bulb neurogenesis as a potential mechanism by performing an in vitro neurosphere assay, in vivo labeling of new cells using BrdU, and in vivo labeling of new cells using a transgenic reporter system. We found that fetal alcohol exposure decreased the number of neural precursor cells in the subependymal zone and the number of new cells in the olfactory bulbs during the first few postnatal weeks. Conclusions Using a combination of techniques, including structural brain imaging, in vitro and in vivo cell detection methods, and behavioral testing, we found that fetal alcohol exposure results in smaller olfactory bulbs and impairments in odor discrimination that persist into adulthood. Furthermore, we found that these abnormalities in olfactory bulb structure and function may arise from deficits in the generation of new olfactory bulb neurons during early postnatal development. PMID:21736737

Specific cesium transport via the Escherichia coli Kup (TrkD) K+ uptake system.

PubMed Central

Bossemeyer, D; Schlösser, A; Bakker, E P

1989-01-01

Escherichia coli cells which contain a functional Kup (formerly TrkD) system took up Cs+ with a moderate rate and affinity. Kup is a separate K+ uptake system with relatively little discrimination in the transport of the cations K+, Rb+, and Cs+. Regardless of the presence or absence of Kup, K+-replete cells took up Cs+ primarily by a very low affinity mode, proportional to the ratio of the Cs+ and K+ concentrations in the medium. PMID:2649491

MALDI imaging mass spectrometry: discrimination of pathophysiological regions in traumatized skeletal muscle by characteristic peptide signatures.

PubMed

Klein, Oliver; Strohschein, Kristin; Nebrich, Grit; Oetjen, Janina; Trede, Dennis; Thiele, Herbert; Alexandrov, Theodore; Giavalisco, Patrick; Duda, Georg N; von Roth, Philipp; Geissler, Sven; Klose, Joachim; Winkler, Tobias

2014-10-01

Due to formation of fibrosis and the loss of contractile muscle tissue, severe muscle injuries often result in insufficient healing marked by a significant reduction of muscle force and motor activity. Our previous studies demonstrated that the local transplantation of mesenchymal stromal cells into an injured skeletal muscle of the rat improves the functional outcome of the healing process. Since, due to the lack of sufficient markers, the accurate discrimination of pathophysiological regions in injured skeletal muscle is inadequate, underlying mechanisms of the beneficial effects of mesenchymal stromal cell transplantation on primary trauma and trauma adjacent muscle area remain elusive. For discrimination of these pathophysiological regions, formalin-fixed injured skeletal muscle tissue was analyzed by MALDI imaging MS. By using two computational evaluation strategies, a supervised approach (ClinProTools) and unsupervised segmentation (SCiLS Lab), characteristic m/z species could be assigned to primary trauma and trauma adjacent muscle regions. Using "bottom-up" MS for protein identification and validation of results by immunohistochemistry, we could identify two proteins, skeletal muscle alpha actin and carbonic anhydrase III, which discriminate between the secondary damage on adjacent tissue and the primary traumatized muscle area. Our results underscore the high potential of MALDI imaging MS to describe the spatial characteristics of pathophysiological changes in muscle. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Combining Raman spectroscopy and digital holographic microscopy for label-free classification of human immune cells (Conference Presentation)

NASA Astrophysics Data System (ADS)

McReynolds, Naomi; Cooke, Fiona G. M.; Chen, Mingzhou; Powis, Simon J.; Dholakia, Kishan

2017-02-01

Moving towards label-free techniques for cell identification is essential for many clinical and research applications. Raman spectroscopy and digital holographic microscopy (DHM) are both label-free, non-destructive optical techniques capable of providing complimentary information. We demonstrate a multi-modal system which may simultaneously take Raman spectra and DHM images to provide both a molecular and a morphological description of our sample. In this study we use Raman spectroscopy and DHM to discriminate between three immune cell populations CD4+ T cells, B cells, and monocytes, which together comprise key functional immune cell subsets in immune responses to invading pathogens. Various parameters that may be used to describe the phase images are also examined such as pixel value histograms or texture analysis. Using our system it is possible to consider each technique individually or in combination. Principal component analysis is used on the data set to discriminate between cell types and leave-one-out cross-validation is used to estimate the efficiency of our method. Raman spectroscopy provides specific chemical information but requires relatively long acquisition times, combining this with a faster modality such as DHM could help achieve faster throughput rates. The combination of these two complimentary optical techniques provides a wealth of information for cell characterisation which is a step towards achieving label free technology for the identification of human immune cells.

An ancillary method in urine cytology: Nucleolar/nuclear volume ratio for discrimination between benign and malignant urothelial cells.

PubMed

Tone, Kiyoshi; Kojima, Keiko; Hoshiai, Keita; Kumagai, Naoya; Kijima, Hiroshi; Kurose, Akira

2016-06-01

The essential of urine cytology for the diagnosis and the follow-up of urothelial neoplasia has been widely recognized. However, there are some cases in which a definitive diagnosis cannot be made due to difficulty in discriminating between benign and malignant. This study evaluated the practicality of nucleolar/nuclear volume ratio (%) for the discrimination. Using Papanicolaou-stained slides, 253 benign urothelial cells and 282 malignant urothelial cells were selected and divided into a benign urothelial cell and an urothelial carcinoma (UC) cell groups. Three suspicious cases and four cases in which discrimination between benign and malignant was difficult were prepared for verification test. Subject cells were decolorized and stained with 4',6-diamidino-2-phenylindole for detection of the nuclei and the nucleoli. Z-stack method was performed to analyze. When the cutoff point of 1.514% discriminating benign urothelial cells and UC cells from nucleolar/nuclear volume ratio (%) was utilized, the sensitivity was 56.0%, the specificity was 88.5%, the positive predictive value was 84.5%, and the negative predictive value was 64.4%. Nuclear and nucleolar volume, number of the nucleoli, and nucleolar/nuclear volume ratio (%) were significantly higher in the UC cell group than in the benign urothelial cell group (P <0.001). In the verification test using the nucleolar/nuclear ratio (%), four of the seven cases were concordant with the final diagnosis. This study analyzed the nuclear and nucleolar volume to establish an index for discrimination of benign and malignant urothelial cells, providing possible additional information in urine cytology. Diagn. Cytopathol. 2016;44:483-491. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Subpopulations of Ig-secreting cells induced by peroxidase immunization: discrimination according to antibody storage and secretion.

PubMed Central

Bernard, J; Jeannesson, P; Thiernesse, N; Zagury, D; Ternynck, T; Avrameas, S

1979-01-01

Mice were injected in their hind footpads with peroxidase (PO) emulsified in Freund's complete adjuvant. The development of cells secreting anti-peroxidase antibody (Ab) and cells secreting immunoglobulins (Ig) were detected in the draining popliteal lymph nodes in the subsequent 35 days, using local haemolysis plaque assay with sheep red cell blood cells coated with either PO or anti-mouse Ig antibody. Plaque-forming cells (PFC) were isolated from the centre of plaques by micromanipulation and after appropriate treatment, were examined by electron microscopy for their intracellular Ab content and in corporation of [3H]-thymidine. Four subpopulations of Ig secreting cells were distinguished: (1) cells secreting Ig without Ab function and not containing intracellular Ab detectable between days 5 and 20; (2) cells secreting Ig without Ab function but containing Ab appearing on day 6 and present throughout the immune response; (3) cells secreting Ab and containing Ab; (4) cells secreting Ab, but without detectable intracellular Ab. These last subpopulations appeared on day 7 and were found in all subsequent assays. The analysis of the kinetics of these subpopulations suggest that cells secreting Ig without Ab function might be precursors of Ab secreting cells. Images Figure 2a Figure 2b Figure 4 PMID:374259

Cooperative synchronized assemblies enhance orientation discrimination.

PubMed

Samonds, Jason M; Allison, John D; Brown, Heather A; Bonds, A B

2004-04-27

There is no clear link between the broad tuning of single neurons and the fine behavioral capabilities of orientation discrimination. We recorded from populations of cells in the cat visual cortex (area 17) to examine whether the joint activity of cells can support finer discrimination than found in individual responses. Analysis of joint firing yields a substantial advantage (i.e., cooperation) in fine-angle discrimination. This cooperation increases to more considerable levels as the population of an assembly is increased. The cooperation in a population of six cells provides encoding of orientation with an information advantage that is at least 2-fold in terms of requiring either fewer cells or less time than independent coding. This cooperation suggests that correlated or synchronized activity can increase information.

Perceived discrimination, family functioning, and depressive symptoms among immigrant women in Taiwan.

PubMed

Yang, Hao-Jan; Wu, Jyun-Yi; Huang, Sheng-Shiung; Lien, Mei-Huei; Lee, Tony Szu-Hsien

2014-10-01

This study examined the moderating effect of family functioning on the relationship between perceived discrimination and depressive symptoms in immigrant women. A total of 239 immigrant women were selected from four administrative regions in Central Taiwan. Questionnaires concerning perceived discrimination, family functioning (including family cohesion and family adaptability), depressive symptoms, and demographic characteristics were completed by either women themselves (N = 120) or their husbands (N = 119). The moderating effect of family functioning on the relationship between perceived discrimination and depression symptoms was analyzed using multiple regression analysis. Findings showed that a higher level of perceived discrimination among immigrant women is associated with more severe depressive symptoms. Family functioning serves as a moderator between the relationship of perceived discrimination and depressive symptoms, but the moderating effect of family adaptability was evident only in data reported by immigrant women. The results indicate that perceived discrimination has negative mental health implications, and also point to the importance of family functioning for depression. Findings suggest that providers should consider addressing immigrant women's mental health needs through declining their psychosocial distress at multiple ecological levels.

Racial discrimination and relationship functioning among African American couples.

PubMed

Lavner, Justin A; Barton, Allen W; Bryant, Chalandra M; Beach, Steven R H

2018-05-21

Racial discrimination is a common stressor for African Americans, with negative consequences for mental and physical well-being. It is likely that these effects extend into the family, but little research has examined the association between racial discrimination and couple functioning. This study used dyadic data from 344 rural, predominantly low-income heterosexual African American couples with an early adolescent child to examine associations between self-reported racial discrimination, psychological and physical aggression, and relationship satisfaction and instability. Experiences of discrimination were common among men and women and were negatively associated with relationship functioning. Specifically, men reported higher levels of psychological aggression and relationship instability if they experienced higher levels of racial discrimination, and women reported higher levels of physical aggression if they experienced higher levels of racial discrimination. All results replicated when controlling for financial hardship, indicating unique effects for discrimination. Findings suggest that racial discrimination may be negatively associated with relationship functioning among African Americans and call for further research on the processes underlying these associations and their long-term consequences. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Presence of FoxP3+ regulatory T Cells predicts outcome of subclinical rejection of renal allografts.

PubMed

Bestard, Oriol; Cruzado, Josep M; Rama, Inés; Torras, Joan; Gomà, Montse; Serón, Daniel; Moreso, Francesc; Gil-Vernet, Salvador; Grinyó, Josep M

2008-10-01

Subclinical rejection (SCR) of renal allografts refers to histologic patterns of acute rejection despite stable renal function. The clinical approach to SCR is controversial; it would be helpful to identify biomarkers that could determine whether the identified cellular infiltrates were detrimental. For investigation of whether the presence of FoxP3+ regulatory T cells (Treg) could help determine the functional importance of tubulointerstitial infiltrates observed in 6-mo protocol biopsies, 37 cases of SCR were evaluated. The presence of FoxP3+ Treg discriminated harmless from injurious infiltrates, evidenced by independently predicting better graft function 2 and 3 yr after transplantation. Furthermore, the FoxP3+ Treg/CD3+ T cell ratio positively correlated with graft function at 2 yr after transplantation, suggesting that an increasing proportion of Treg within the global T cell infiltrate may facilitate renal engraftment; therefore, immunostaining for FoxP3+ Treg in patients with SCR on protocol biopsies may ultimately be useful to identify patients who may require alterations in their immunosuppressive regimens.

Presence of FoxP3+ Regulatory T Cells Predicts Outcome of Subclinical Rejection of Renal Allografts

PubMed Central

Bestard, Oriol; Cruzado, Josep M.; Rama, Inés; Torras, Joan; Gomà, Montse; Serón, Daniel; Moreso, Francesc; Gil-Vernet, Salvador; Grinyó, Josep M.

2008-01-01

Subclinical rejection (SCR) of renal allografts refers to histologic patterns of acute rejection despite stable renal function. The clinical approach to SCR is controversial; it would be helpful to identify biomarkers that could determine whether the identified cellular infiltrates were detrimental. For investigation of whether the presence of FoxP3+ regulatory T cells (Treg) could help determine the functional importance of tubulointerstitial infiltrates observed in 6-mo protocol biopsies, 37 cases of SCR were evaluated. The presence of FoxP3+ Treg discriminated harmless from injurious infiltrates, evidenced by independently predicting better graft function 2 and 3 yr after transplantation. Furthermore, the FoxP3+ Treg/CD3+ T cell ratio positively correlated with graft function at 2 yr after transplantation, suggesting that an increasing proportion of Treg within the global T cell infiltrate may facilitate renal engraftment; therefore, immunostaining for FoxP3+ Treg in patients with SCR on protocol biopsies may ultimately be useful to identify patients who may require alterations in their immunosuppressive regimens. PMID:18495961

Human skin is protected by four functionally and phenotypically discrete populations of resident and recirculating memory T cells.

PubMed

Watanabe, Rei; Gehad, Ahmed; Yang, Chao; Scott, Laura L; Teague, Jessica E; Schlapbach, Christoph; Elco, Christopher P; Huang, Victor; Matos, Tiago R; Kupper, Thomas S; Clark, Rachael A

2015-03-18

The skin of an adult human contains about 20 billion memory T cells. Epithelial barrier tissues are infiltrated by a combination of resident and recirculating T cells in mice, but the relative proportions and functional activities of resident versus recirculating T cells have not been evaluated in human skin. We discriminated resident from recirculating T cells in human-engrafted mice and lymphoma patients using alemtuzumab, a medication that depletes recirculating T cells from skin, and then analyzed these T cell populations in healthy human skin. All nonrecirculating resident memory T cells (TRM) expressed CD69, but most were CD4(+), CD103(-), and located in the dermis, in contrast to studies in mice. Both CD4(+) and CD8(+) CD103(+) TRM were enriched in the epidermis, had potent effector functions, and had a limited proliferative capacity compared to CD103(-) TRM. TRM of both types had more potent effector functions than recirculating T cells. We observed two distinct populations of recirculating T cells, CCR7(+)/L-selectin(+) central memory T cells (TCM) and CCR7(+)/L-selectin(-) T cells, which we term migratory memory T cells (TMM). Circulating skin-tropic TMM were intermediate in cytokine production between TCM and effector memory T cells. In patients with cutaneous T cell lymphoma, malignant TCM and TMM induced distinct inflammatory skin lesions, and TMM were depleted more slowly from skin after alemtuzumab, suggesting that TMM may recirculate more slowly. In summary, human skin is protected by four functionally distinct populations of T cells, two resident and two recirculating, with differing territories of migration and distinct functional activities. Copyright © 2015, American Association for the Advancement of Science.

Hox2 Genes Are Required for Tonotopic Map Precision and Sound Discrimination in the Mouse Auditory Brainstem.

PubMed

Karmakar, Kajari; Narita, Yuichi; Fadok, Jonathan; Ducret, Sebastien; Loche, Alberto; Kitazawa, Taro; Genoud, Christel; Di Meglio, Thomas; Thierry, Raphael; Bacelo, Joao; Lüthi, Andreas; Rijli, Filippo M

2017-01-03

Tonotopy is a hallmark of auditory pathways and provides the basis for sound discrimination. Little is known about the involvement of transcription factors in brainstem cochlear neurons orchestrating the tonotopic precision of pre-synaptic input. We found that in the absence of Hoxa2 and Hoxb2 function in Atoh1-derived glutamatergic bushy cells of the anterior ventral cochlear nucleus, broad input topography and sound transmission were largely preserved. However, fine-scale synaptic refinement and sharpening of isofrequency bands of cochlear neuron activation upon pure tone stimulation were impaired in Hox2 mutants, resulting in defective sound-frequency discrimination in behavioral tests. These results establish a role for Hox factors in tonotopic refinement of connectivity and in ensuring the precision of sound transmission in the mammalian auditory circuit. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Light collection and pulse-shape discrimination in elongated scintillator cells for the PROSPECT reactor antineutrino experiment

NASA Astrophysics Data System (ADS)

Ashenfelter, J.; Balantekin, B.; Band, H. R.; Barclay, G.; Bass, C. D.; Berish, D.; Bowden, N. S.; Bowes, A.; Brodsky, J. P.; Bryan, C. D.; Cherwinka, J. J.; Chu, R.; Classen, T.; Commeford, K.; Davee, D.; Dean, D.; Deichert, G.; Diwan, M. V.; Dolinski, M. J.; Dolph, J.; Dwyer, D. A.; Gaison, J. K.; Galindo-Uribarri, A.; Gilje, K.; Glenn, A.; Goddard, B. W.; Green, M.; Han, K.; Hans, S.; Heeger, K. M.; Heffron, B.; Jaffe, D. E.; Langford, T. J.; Littlejohn, B. R.; Martinez Caicedo, D. A.; McKeown, R. D.; Mendenhall, M. P.; Mueller, P.; Mumm, H. P.; Napolitano, J.; Neilson, R.; Norcini, D.; Pushin, D.; Qian, X.; Romero, E.; Rosero, R.; Saldana, L.; Seilhan, B. S.; Sharma, R.; Sheets, S.; Stemen, N. T.; Surukuchi, P. T.; Varner, R. L.; Viren, B.; Wang, W.; White, B.; White, C.; Wilhelmi, J.; Williams, C.; Wise, T.; Yao, H.; Yeh, M.; Yen, Y. R.; Zangakis, G.; Zhang, C.; Zhang, X.

2015-11-01

A meter-long, 23-liter EJ-309 liquid scintillator detector has been constructed to study the light collection and pulse-shape discrimination performance of elongated scintillator cells for the PROSPECT reactor antineutrino experiment. The magnitude and uniformity of light collection and neutron-gamma discrimination power in the energy range of antineutrino inverse beta decay products have been studied using gamma and spontaneous fission calibration sources deployed along the cell axis. We also study neutron-gamma discrimination and light collection abilities for differing PMT and reflector configurations. Key design features for optimizing MeV-scale response and background rejection capabilities are identified.

All-In-One: Advanced preparation of Human Parenchymal and Non-Parenchymal Liver Cells.

PubMed

Werner, Melanie; Driftmann, Sabrina; Kleinehr, Kathrin; Kaiser, Gernot M; Mathé, Zotlan; Treckmann, Juergen-Walter; Paul, Andreas; Skibbe, Kathrin; Timm, Joerg; Canbay, Ali; Gerken, Guido; Schlaak, Joerg F; Broering, Ruth

2015-01-01

Liver cells are key players in innate immunity. Thus, studying primary isolated liver cells is necessary for determining their role in liver physiology and pathophysiology. In particular, the quantity and quality of isolated cells are crucial to their function. Our aim was to isolate a large quantity of high-quality human parenchymal and non-parenchymal cells from a single liver specimen. Hepatocytes, Kupffer cells, liver sinusoidal endothelial cells, and stellate cells were isolated from liver tissues by collagenase perfusion in combination with low-speed centrifugation, density gradient centrifugation, and magnetic-activated cell sorting. The purity and functionality of cultured cell populations were controlled by determining their morphology, discriminative cell marker expression, and functional activity. Cell preparation yielded the following cell counts per gram of liver tissue: 2.0 ± 0.4 × 10(7) hepatocytes, 1.8 ± 0.5 × 10(6 )Kupffer cells, 4.3 ± 1.9 × 10(5) liver sinusoidal endothelial cells, and 3.2 ± 0.5 × 10(5) stellate cells. Hepatocytes were identified by albumin (95.5 ± 1.7%) and exhibited time-dependent activity of cytochrome P450 enzymes. Kupffer cells expressed CD68 (94.5 ± 1.2%) and exhibited phagocytic activity, as determined with 1 μm latex beads. Endothelial cells were CD146(+) (97.8 ± 1.1%) and exhibited efficient uptake of acetylated low-density lipoprotein. Hepatic stellate cells were identified by the expression of α-smooth muscle actin (97.1 ± 1.5%). These cells further exhibited retinol (vitamin A)-mediated autofluorescence. Our isolation procedure for primary parenchymal and non-parenchymal liver cells resulted in cell populations of high purity and quality, with retained physiological functionality in vitro. Thus, this system may provide a valuable tool for determining liver function and disease.

Biophotonics sensor acclimatization to stem cells environment

NASA Astrophysics Data System (ADS)

Mohamad Shahimin, Mukhzeer

2017-11-01

The ability to discriminate, characterise and purify biological cells from heterogeneous population of cells is fundamental to numerous prognosis and diagnosis applications; often forming the basis for current and emerging clinical protocols in stem cell therapy. Current sorting approaches exploit differences in cell density, specific immunologic targets, or receptor-ligand interactions to isolate particular cells. Identification of novel properties by which different cell types may be discerned and of new ways for their selective manipulation are clearly fundamental components for improving sorting methodologies. Biophotonics sensor developed by our team are potentially capable of discriminating cells according to their refractive index (which is highly dependable on the organelles inside the cell), size (indicator to cell stage) and shape (in certain cases as an indicator to cell type). The sensor, which already discriminate particles efficiently, is modified to acclimatize into biological environment, especially for stem cell applications.

Label-free screening of niche-to-niche variation in satellite stem cells using functionalized pores

NASA Astrophysics Data System (ADS)

Chapman, Matthew R.; Balakrishnan, Karthik; Conboy, Michael J.; Mohanty, Swomitra; Jabart, Eric; Huang, Haiyan; Hack, James; Conboy, Irina M.; Sohn, Lydia L.

2012-02-01

Combinations of surface markers are currently used to identify muscle satellite cells. Using pores functionalized with specific antibodies and measuring the transit time of cells passing through these pores, we discovered remarkable heterogeneity in the expression of these markers in muscle (satellite) stem cells that reside in different single myofibers. Microniche-specific variation in stem cells of the same organ has not been previously described, as bulk analysis does not discriminate between separate myofibers or even separate hind-leg muscle groups. We found a significant population of Sca-1+ satellite cells that form myotubes, thereby demonstrating the myogenic potential of Sca-1+ cells, which are currently excluded in bulk sorting. Finally, using our label-free pore screening technique, we have been able to quantify directly surface expression of Notch1 without activation of the Notch pathway. We show for the first time Notch1-expression heterogeneity in unactivated satellite cells. The discovery of fiber-to-fiber variations prompts new research into the reasons for such diversity in muscle stem cells.

Return of Function after Hair Cell Regeneration

PubMed Central

Ryals, Brenda M.; Dent, Micheal L.; Dooling, Robert J.

2012-01-01

The ultimate goal of hair cell regeneration is to restore functional hearing. Because birds begin perceiving and producing song early in life, they provide a propitious model for studying not only whether regeneration of lost hair cells can return auditory sensitivity but also whether this regenerated periphery can restore complex auditory perception and production. They are the only animal where hair cell regeneration occurs naturally after hair cell loss and where the ability to correctly perceive and produce complex acoustic signals is critical to procreation and survival. The purpose of this review article is to survey the most recent literature on behavioral measures of auditory functional return in adult birds after hair cell regeneration. The first portion of the review summarizes the effect of ototoxic drug induced hair cell loss and regeneration on hearing loss and recovery for pure tones. The second portion reviews studies of complex, species-specific vocalization discrimination and recognition after hair cell regeneration. Finally, we discuss the relevance of temporary hearing loss and recovery through hair cell regeneration on complex call and song production. Hearing sensitivity is restored, except for the highest frequencies, after hair cell regeneration in birds, but there are enduring changes to complex auditory perception. These changes do not appear to provide any obstacle to future auditory or vocal learning. PMID:23202051

Joint Entropy for Space and Spatial Frequency Domains Estimated from Psychometric Functions of Achromatic Discrimination

PubMed Central

Silveira, Vladímir de Aquino; Souza, Givago da Silva; Gomes, Bruno Duarte; Rodrigues, Anderson Raiol; Silveira, Luiz Carlos de Lima

2014-01-01

We used psychometric functions to estimate the joint entropy for space discrimination and spatial frequency discrimination. Space discrimination was taken as discrimination of spatial extent. Seven subjects were tested. Gábor functions comprising unidimensionalsinusoidal gratings (0.4, 2, and 10 cpd) and bidimensionalGaussian envelopes (1°) were used as reference stimuli. The experiment comprised the comparison between reference and test stimulithat differed in grating's spatial frequency or envelope's standard deviation. We tested 21 different envelope's standard deviations around the reference standard deviation to study spatial extent discrimination and 19 different grating's spatial frequencies around the reference spatial frequency to study spatial frequency discrimination. Two series of psychometric functions were obtained for 2%, 5%, 10%, and 100% stimulus contrast. The psychometric function data points for spatial extent discrimination or spatial frequency discrimination were fitted with Gaussian functions using the least square method, and the spatial extent and spatial frequency entropies were estimated from the standard deviation of these Gaussian functions. Then, joint entropy was obtained by multiplying the square root of space extent entropy times the spatial frequency entropy. We compared our results to the theoretical minimum for unidimensional Gábor functions, 1/4π or 0.0796. At low and intermediate spatial frequencies and high contrasts, joint entropy reached levels below the theoretical minimum, suggesting non-linear interactions between two or more visual mechanisms. We concluded that non-linear interactions of visual pathways, such as the M and P pathways, could explain joint entropy values below the theoretical minimum at low and intermediate spatial frequencies and high contrasts. These non-linear interactions might be at work at intermediate and high contrasts at all spatial frequencies once there was a substantial decrease in joint entropy for these stimulus conditions when contrast was raised. PMID:24466158

Joint entropy for space and spatial frequency domains estimated from psychometric functions of achromatic discrimination.

PubMed

Silveira, Vladímir de Aquino; Souza, Givago da Silva; Gomes, Bruno Duarte; Rodrigues, Anderson Raiol; Silveira, Luiz Carlos de Lima

2014-01-01

We used psychometric functions to estimate the joint entropy for space discrimination and spatial frequency discrimination. Space discrimination was taken as discrimination of spatial extent. Seven subjects were tested. Gábor functions comprising unidimensionalsinusoidal gratings (0.4, 2, and 10 cpd) and bidimensionalGaussian envelopes (1°) were used as reference stimuli. The experiment comprised the comparison between reference and test stimulithat differed in grating's spatial frequency or envelope's standard deviation. We tested 21 different envelope's standard deviations around the reference standard deviation to study spatial extent discrimination and 19 different grating's spatial frequencies around the reference spatial frequency to study spatial frequency discrimination. Two series of psychometric functions were obtained for 2%, 5%, 10%, and 100% stimulus contrast. The psychometric function data points for spatial extent discrimination or spatial frequency discrimination were fitted with Gaussian functions using the least square method, and the spatial extent and spatial frequency entropies were estimated from the standard deviation of these Gaussian functions. Then, joint entropy was obtained by multiplying the square root of space extent entropy times the spatial frequency entropy. We compared our results to the theoretical minimum for unidimensional Gábor functions, 1/4π or 0.0796. At low and intermediate spatial frequencies and high contrasts, joint entropy reached levels below the theoretical minimum, suggesting non-linear interactions between two or more visual mechanisms. We concluded that non-linear interactions of visual pathways, such as the M and P pathways, could explain joint entropy values below the theoretical minimum at low and intermediate spatial frequencies and high contrasts. These non-linear interactions might be at work at intermediate and high contrasts at all spatial frequencies once there was a substantial decrease in joint entropy for these stimulus conditions when contrast was raised.

Illuminating cellular structure and function in the early secretory pathway by multispectral 3D imaging in living cells

NASA Astrophysics Data System (ADS)

Rietdorf, Jens; Stephens, David J.; Squire, Anthony; Simpson, Jeremy; Shima, David T.; Paccaud, Jean-Pierre; Bastiaens, Philippe I.; Pepperkok, Rainer

2000-04-01

Membrane traffic between the endoplasmic reticulum (ER) and the Golgi complex is regulated by two vesicular coat complexes, COPII and COPI. COPII has been implicated in selective packaging of anterograde cargo into coated transport vesicles budding from the ER. COPI-coated vesicles are proposed to mediate recycling of proteins from the Golgi complex to the ER. We have used multi spectral 3D imaging to visualize COPI and COPII behavior simultaneously with various GFP-tagged secretory markers in living cells. This shows that COPII and COPI act sequentially whereby COPI association with anterograde transport complexes is involved in microtubule-based transport and the en route segregation of ER recycling molecules from secretory cargo within TCS in transit to the Golgi complex. We have also investigated the possibility to discriminate spectrally GFP fusion proteins by fluorescence lifetime imaging. This shows that at least two, and possibly up to three GFP fusion proteins can be discriminated and localized in living cells using a single excitation wavelength and a single broad band emission filter.

Racial Identity Matters: The Relationship between Racial Discrimination and Psychological Functioning in African American Adolescents

ERIC Educational Resources Information Center

Sellers, Robert M.; Copeland-Linder, Nikeea; Martin, Pamela P.; Lewis, R. L'Heureux

2006-01-01

This study examines the interrelationships among racial discrimination, racial identity, and psychological functioning in a sample of 314 African American adolescents. Racial discrimination was associated with lower levels of psychological functioning as measured by perceived stress, depressive symptomatology, and psychological well-being.…

Light collection and pulse-shape discrimination in elongated scintillator cells for the PROSPECT reactor antineutrino experiment

DOE PAGES

Ashenfelter, J.; Jaffe, D.; Diwan, M. V.; ...

2015-11-06

A meter-long, 23-liter EJ-309 liquid scintillator detector has been constructed to study the light collection and pulse-shape discrimination performance of elongated scintillator cells for the PROSPECT reactor antineutrino experiment. The magnitude and uniformity of light collection and neutron-gamma discrimination power in the energy range of antineutrino inverse beta decay products have been studied using gamma and spontaneous fission calibration sources deployed along the cell axis. We also study neutron-gamma discrimination and light collection abilities for differing PMT and reflector configurations. As a result, key design features for optimizing MeV-scale response and background rejection capabilities are identified.

Assessment of contrast gain signature in inferred magnocellular and parvocellular pathways in patients with glaucoma

PubMed Central

Sun, Hao; Swanson, William H.; Arvidson, Brian; Dul, Mitchell W.

2010-01-01

PURPOSE Contrast gain signatures of inferred magnocellular and parvocellular postreceptoral pathways were assessed for patients with glaucoma using a contrast discrimination paradigm developed by Pokorny and Smith. The potential causes for changes in contrast gain signature were investigated using model simulations of ganglion cell contrast responses. METHODS Foveal contrast discrimination thresholds were measured with a pedestal-Δ-pedestal paradigm developed by Pokorny and Smith (1997). Stimuli were 27 msec luminance increments superimposed on 227 msec pulsed Δ-pedestals. Contrast thresholds and contrast gain signatures mediated by the inferred magnocellular (MC) and parvocellular (PC) pathways were assessed using linear fits to contrast discrimination thresholds at either lower or higher Δ-pedestal contrasts, respectively. Twenty-seven patients with glaucoma were tested, as well as 16 age-similar control subjects free of eye disease. RESULTS Contrast sensitivity and contrast gain signature mediated by the inferred MC pathway were lower for the glaucoma group, and reduced contrast gain signature was correlated with reduced contrast sensitivity (r2=45%, p<0.0005). These two parameters mediated by the inferred PC pathway were little affected for the glaucoma group. Model simulations suggest that the reduced contrast sensitivity and contrast gain signature were consistent with the hypothesis that reduced MC ganglion cell dendritic complexity can lead to reduced effective retinal illuminance, and hence increased semi-saturation contrast of the ganglion cell contrast response functions. CONCLUSIONS The contrast sensitivity and contrast gain signature of the inferred MC pathway were reduced in patients with glaucoma. The results were consistent with a model of ganglion cell dysfunction due to reduced synaptic density. PMID:18501947

Characterizing cellular mechanical phenotypes with mechano-node-pore sensing

PubMed Central

Kim, Junghyun; Han, Sewoon; Lei, Andy; Miyano, Masaru; Bloom, Jessica; Srivastava, Vasudha; Stampfer, Martha M.; Gartner, Zev J.; LaBarge, Mark A.; Sohn, Lydia L.

2018-01-01

The mechanical properties of cells change with their differentiation, chronological age, and malignant progression. Consequently, these properties may be useful label-free biomarkers of various functional or clinically relevant cell states. Here, we demonstrate mechano-node-pore sensing (mechano-NPS), a multi-parametric single-cell-analysis method that utilizes a four-terminal measurement of the current across a microfluidic channel to quantify simultaneously cell diameter, resistance to compressive deformation, transverse deformation under constant strain, and recovery time after deformation. We define a new parameter, the whole-cell deformability index (wCDI), which provides a quantitative mechanical metric of the resistance to compressive deformation that can be used to discriminate among different cell types. The wCDI and the transverse deformation under constant strain show malignant MCF-7 and A549 cell lines are mechanically distinct from non-malignant, MCF-10A and BEAS-2B cell lines, and distinguishes between cells treated or untreated with cytoskeleton-perturbing small molecules. We categorize cell recovery time, ΔTr, as instantaneous (ΔTr ~ 0 ms), transient (ΔTr ≤ 40ms), or prolonged (ΔTr > 40ms), and show that the composition of recovery types, which is a consequence of changes in cytoskeletal organization, correlates with cellular transformation. Through the wCDI and cell-recovery time, mechano-NPS discriminates between sub-lineages of normal primary human mammary epithelial cells with accuracy comparable to flow cytometry, but without antibody labeling. Mechano-NPS identifies mechanical phenotypes that distinguishes lineage, chronological age, and stage of malignant progression in human epithelial cells. PMID:29780657

Computer-assisted sperm morphometry fluorescence-based analysis has potential to determine progeny sex.

PubMed

Santolaria, Pilar; Pauciullo, Alfredo; Silvestre, Miguel A; Vicente-Fiel, Sandra; Villanova, Leyre; Pinton, Alain; Viruel, Juan; Sales, Ester; Yániz, Jesús L

2016-01-01

This study was designed to determine the ability of computer-assisted sperm morphometry analysis (CASA-Morph) with fluorescence to discriminate between spermatozoa carrying different sex chromosomes from the nuclear morphometrics generated and different statistical procedures in the bovine species. The study was divided into two experiments. The first was to study the morphometric differences between X- and Y-chromosome-bearing spermatozoa (SX and SY, respectively). Spermatozoa from eight bulls were processed to assess simultaneously the sex chromosome by FISH and sperm morphometry by fluorescence-based CASA-Morph. SX cells were larger than SY cells on average (P < 0.001) although with important differences between bulls. A simultaneous evaluation of all the measured features by discriminant analysis revealed that nuclear area and average fluorescence intensity were the variables selected by stepwise discriminant function analysis as the best discriminators between SX and SY. In the second experiment, the sperm nuclear morphometric results from CASA-Morph in nonsexed (mixed SX and SY) and sexed (SX) semen samples from four bulls were compared. FISH allowed a successful classification of spermatozoa according to their sex chromosome content. X-sexed spermatozoa displayed a larger size and fluorescence intensity than nonsexed spermatozoa (P < 0.05). We conclude that the CASA-Morph fluorescence-based method has the potential to find differences between X- and Y-chromosome-bearing spermatozoa in bovine species although more studies are needed to increase the precision of sex determination by this technique.

The self-nonself discrimination and the nature and acquisition of the antibody repertoire.

PubMed

Coutinho, A

1980-01-01

Network ideas are confronted with current hypotheses for the origin of antibody diversity and self-nonself discrimination. The difficulties of reconciling the promethean evolution of the antibody system with "germ line" theories are discussed, as well as the problems of "somatic" hypotheses to explain the completeness of the antibody repertoire. The formal incompatibility of the network theory with ideas basing self-nonself discrimination on the elimination of self-reactive cells is demonstrated, as well as the difficulties of these and other environment-dependent hypotheses for lymphocyte activation, to encompass the internal activity in the immune system. It is argued, on the other hand, that the limitations of the network theory in providing a functional basis for the idiotypic network and in accounting for self-nonself discrimination, can be solved by finding in a complete repertoire of antibody-combining sites the complementary structures to growth receptors on B lymphocytes, and by using these as internal mitogens in the expansion of the precursor cell pools and in the maintenance of the mature steady states. Letting self-nonself discrimination be accounted for by such growth receptors, both the integrity of the antibody repertoire and the internal activity in the system can also be ensured. Moreover, by postulating a germ line origin for the antireceptor antibodies and by accepting idiotypic cross-reactivity between growth receptors and other germ line antibodies, the possibilities are set for a phylogenetically and ontogenically autonomous immune system embodied with the capabilities for self-expansion, diversification and selection of available repertoires. Its promethean characteristics are explained by its completeness, and this is achieved by idiotypic interactions between growth receptors and a limited number of complementary or cross-reactive germ line antibodies, naturally selected on the basis of their structural relationships with growth receptors.

Tissue adaptation: Implications for gut immunity and tolerance

PubMed Central

2017-01-01

Tissue adaptation is an intrinsic component of immune cell development, influencing both resistance to pathogens and tolerance. Chronically stimulated surfaces of the body, in particular the gut mucosa, are the major sites where immune cells traffic and reside. Their adaptation to these environments requires constant discrimination between natural stimulation coming from harmless microbiota and food, and pathogens that need to be cleared. This review will focus on the adaptation of lymphocytes to the gut mucosa, a highly specialized environment that can help us understand the plasticity of leukocytes arriving at various tissue sites and how tissue-related factors operate to shape immune cell fate and function. PMID:28432200

Functionalized nanopipettes: toward label-free, single cell biosensors.

PubMed

Actis, Paolo; Mak, Andy C; Pourmand, Nader

2010-08-01

Nanopipette technology has been proven to be a label-free biosensor capable of identifying DNA and proteins. The nanopipette can include specific recognition elements for analyte discrimination based on size, shape, and charge density. The fully electrical read-out and the ease and low-cost fabrication are unique features that give this technology an enormous potential. Unlike other biosensing platforms, nanopipettes can be precisely manipulated with submicron accuracy and used to study single cell dynamics. This review is focused on creative applications of nanopipette technology for biosensing. We highlight the potential of this technology with a particular attention to integration of this biosensor with single cell manipulation platforms.

Functionalized nanopipettes: toward label-free, single cell biosensors

PubMed Central

Actis, Paolo; Mak, Andy C.

2010-01-01

Nanopipette technology has been proven to be a label-free biosensor capable of identifying DNA and proteins. The nanopipette can include specific recognition elements for analyte discrimination based on size, shape, and charge density. The fully electrical read-out and the ease and low-cost fabrication are unique features that give this technology an enormous potential. Unlike other biosensing platforms, nanopipettes can be precisely manipulated with submicron accuracy and used to study single cell dynamics. This review is focused on creative applications of nanopipette technology for biosensing. We highlight the potential of this technology with a particular attention to integration of this biosensor with single cell manipulation platforms. PMID:20730113

Discriminant analysis of resting-state functional connectivity patterns on the Grassmann manifold

NASA Astrophysics Data System (ADS)

Fan, Yong; Liu, Yong; Jiang, Tianzi; Liu, Zhening; Hao, Yihui; Liu, Haihong

2010-03-01

The functional networks, extracted from fMRI images using independent component analysis, have been demonstrated informative for distinguishing brain states of cognitive functions and neurological diseases. In this paper, we propose a novel algorithm for discriminant analysis of functional networks encoded by spatial independent components. The functional networks of each individual are used as bases for a linear subspace, referred to as a functional connectivity pattern, which facilitates a comprehensive characterization of temporal signals of fMRI data. The functional connectivity patterns of different individuals are analyzed on the Grassmann manifold by adopting a principal angle based subspace distance. In conjunction with a support vector machine classifier, a forward component selection technique is proposed to select independent components for constructing the most discriminative functional connectivity pattern. The discriminant analysis method has been applied to an fMRI based schizophrenia study with 31 schizophrenia patients and 31 healthy individuals. The experimental results demonstrate that the proposed method not only achieves a promising classification performance for distinguishing schizophrenia patients from healthy controls, but also identifies discriminative functional networks that are informative for schizophrenia diagnosis.

Characterizing differences between MSCs and TM cells: Toward autologous stem cell therapies for the glaucomatous trabecular meshwork.

PubMed

Snider, Eric J; Vannatta, R Taylor; Schildmeyer, Lisa; Stamer, W Daniel; Ethier, C Ross

2018-03-01

Glaucoma, a leading cause of blindness, is characterized by an increase in intraocular pressure, which is largely determined by resistance to aqueous humour outflow through the trabecular meshwork (TM). In glaucoma, the cellularity of the TM is decreased, and, as a result, stem cell therapies for the TM represent a potential therapeutic option for restoring TM function and treating glaucoma patients. We here focus on adipose derived mesenchymal stem cells (MSCs) as a potential autologous cell source for TM regenerative medicine applications and describe characterization techniques at the messenger (reverse transcription-quantitative polymerase chain reaction), protein (western blotting, flow cytometry), and functional (contractility, phagocytosis) levels to distinguish MSCs from TM cells. We present a panel of 12 transcripts to allow: (a) suitable normalization of reverse transcription-quantitative polymerase chain reaction results across cell types and after exposure to potential differentiation stimuli; (b) distinguishing MSCs from TM cells; (c) distinguishing subtypes of TM cells; and (d) distinguishing TM cells from those in neighbouring tissue. At the protein level, dexamethasone induction of myocilin was a robust discriminating factor between MSCs and TM cells and was complemented by other protein markers. Finally, we show that contractility and phagocytosis differ between MSCs and TM cells. These methods are recommended for use in future differentiation studies to fully define if a functional TM-like phenotype is being achieved. Copyright © 2017 John Wiley & Sons, Ltd.

Coding of auditory temporal and pitch information by hippocampal individual cells and cell assemblies in the rat.

PubMed

Sakurai, Y

2002-01-01

This study reports how hippocampal individual cells and cell assemblies cooperate for neural coding of pitch and temporal information in memory processes for auditory stimuli. Each rat performed two tasks, one requiring discrimination of auditory pitch (high or low) and the other requiring discrimination of their duration (long or short). Some CA1 and CA3 complex-spike neurons showed task-related differential activity between the high and low tones in only the pitch-discrimination task. However, without exception, neurons which showed task-related differential activity between the long and short tones in the duration-discrimination task were always task-related neurons in the pitch-discrimination task. These results suggest that temporal information (long or short), in contrast to pitch information (high or low), cannot be coded independently by specific neurons. The results also indicate that the two different behavioral tasks cannot be fully differentiated by the task-related single neurons alone and suggest a model of cell-assembly coding of the tasks. Cross-correlation analysis among activities of simultaneously recorded multiple neurons supported the suggested cell-assembly model.Considering those results, this study concludes that dual coding by hippocampal single neurons and cell assemblies is working in memory processing of pitch and temporal information of auditory stimuli. The single neurons encode both auditory pitches and their temporal lengths and the cell assemblies encode types of tasks (contexts or situations) in which the pitch and the temporal information are processed.

A discriminant function model as an alternative method to spirometry for COPD screening in primary care settings in China.

PubMed

Cui, Jiangyu; Zhou, Yumin; Tian, Jia; Wang, Xinwang; Zheng, Jingping; Zhong, Nanshan; Ran, Pixin

2012-12-01

COPD is often underdiagnosed in a primary care setting where the spirometry is unavailable. This study was aimed to develop a simple, economical and applicable model for COPD screening in those settings. First we established a discriminant function model based on Bayes' Rule by stepwise discriminant analysis, using the data from 243 COPD patients and 112 non-COPD subjects from our COPD survey in urban and rural communities and local primary care settings in Guangdong Province, China. We then used this model to discriminate COPD in additional 150 subjects (50 non-COPD and 100 COPD ones) who had been recruited by the same methods as used to have established the model. All participants completed pre- and post-bronchodilator spirometry and questionnaires. COPD was diagnosed according to the Global Initiative for Chronic Obstructive Lung Disease criteria. The sensitivity and specificity of the discriminant function model was assessed. THE ESTABLISHED DISCRIMINANT FUNCTION MODEL INCLUDED NINE VARIABLES: age, gender, smoking index, body mass index, occupational exposure, living environment, wheezing, cough and dyspnoea. The sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, accuracy and error rate of the function model to discriminate COPD were 89.00%, 82.00%, 4.94, 0.13, 86.66% and 13.34%, respectively. The accuracy and Kappa value of the function model to predict COPD stages were 70% and 0.61 (95% CI, 0.50 to 0.71). This discriminant function model may be used for COPD screening in primary care settings in China as an alternative option instead of spirometry.

The association of optimism and perceived discrimination with health care utilization in adults with sickle cell disease.

PubMed

Stanton, Michael V; Jonassaint, Charles R; Bartholomew, Frederick B; Edwards, Christopher; Richman, Laura; DeCastro, Laura; Williams, Redford

2010-11-01

We evaluated the effect of perceived discrimination, optimism, and their interaction on health care utilization among African American adults with sickle cell disease (SCD). Measures of optimism and perceived discrimination were obtained in 49 African American SCD patients. Multiple regression analyses controlling for sex and age tested effects of optimism and perceived discrimination on the number of emergency department visits (ED) and number and duration of hospitalizations over the past year. A perceived discrimination-optimism interaction was associated with number of emergency departments visits (b = .29, p = .052), number of hospitalizations (b = .36, p = .019), and duration of hospitalizations (b = .30, p = .045) such that those with high perceived discrimination/high optimism had the greatest health care utilization. African American SCD patients with high perceived discrimination/high optimism had greater health care utilization than patients who reported either low perceived discrimination or low optimism. This study suggests that patient personality and coping styles should be considered when evaluating the effects of stress on SCD-related outcomes.

Functional Analysis of Corn Husk Photosynthesis[W][OA

PubMed Central

Pengelly, Jasper J.L.; Kwasny, Scott; Bala, Soumi; Evans, John R.; Voznesenskaya, Elena V.; Koteyeva, Nuria K.; Edwards, Gerald E.; Furbank, Robert T.; von Caemmerer, Susanne

2011-01-01

The husk surrounding the ear of corn/maize (Zea mays) has widely spaced veins with a number of interveinal mesophyll (M) cells and has been described as operating a partial C3 photosynthetic pathway, in contrast to its leaves, which use the C4 photosynthetic pathway. Here, we characterized photosynthesis in maize husk and leaf by measuring combined gas exchange and carbon isotope discrimination, the oxygen dependence of the CO2 compensation point, and photosynthetic enzyme activity and localization together with anatomy. The CO2 assimilation rate in the husk was less than that in the leaves and did not saturate at high CO2, indicating CO2 diffusion limitations. However, maximal photosynthetic rates were similar between the leaf and husk when expressed on a chlorophyll basis. The CO2 compensation points of the husk were high compared with the leaf but did not vary with oxygen concentration. This and the low carbon isotope discrimination measured concurrently with gas exchange in the husk and leaf suggested C4-like photosynthesis in the husk. However, both Rubisco activity and the ratio of phosphoenolpyruvate carboxylase to Rubisco activity were reduced in the husk. Immunolocalization studies showed that phosphoenolpyruvate carboxylase is specifically localized in the layer of M cells surrounding the bundle sheath cells, while Rubisco and glycine decarboxylase were enriched in bundle sheath cells but also present in M cells. We conclude that maize husk operates C4 photosynthesis dispersed around the widely spaced veins (analogous to leaves) in a diffusion-limited manner due to low M surface area exposed to intercellular air space, with the functional role of Rubisco and glycine decarboxylase in distant M yet to be explained. PMID:21511990

Human skin is protected by four functionally and phenotypically discrete populations of resident and recirculating memory T cells

PubMed Central

Watanabe, Rei; Gehad, Ahmed; Yang, Chao; Campbell, Laura; Teague, Jessica E.; Schlapbach, Christoph; Elco, Christopher; Huang, Victor; Matos, Tiago R.; Kupper, Thomas S.; Clark, Rachael A.

2015-01-01

The skin of an adult human contains approximately 20 billion memory T cells. Epithelial barrier tissues are infiltrated by a combination of resident and recirculating T cells in mice but the relative proportions and functional activities of resident versus recirculating T cells have not been evaluated in human skin. We discriminated resident from recirculating T cells in human engrafted mice and lymphoma patients using alemtuzumab, a medication that depletes recirculating T cells from skin, and then analyzed these T cell populations in healthy human skin. All non-recirculating resident memory T cells (TRM) expressed CD69, but the majority were CD4+, CD103− and located in the dermis, in contrast to studies in mice. Both CD4+ and CD8+ CD103+ TRM were enriched in the epidermis, had potent effector functions and had a limited proliferative capacity compared to CD103− TRM. TRM of both types had more potent effector functions than recirculating T cells. Induction of CD103 on human T cells was enhanced by keratinocyte contact, depended on TGFβ and was independent of T cell keratinocyte adhesive interactions. We observed two distinct populations of recirculating T cells, CCR7+/L-selectin+ central memory T cells (TCM) and CCR7+/L-selectin− T cells, which we term migratory memory T cells (TMM). Circulating skin-tropic TMM were intermediate in cytokine production between TCM and effector memory T cells. In patients with cutaneous T cell lymphoma, malignant TCM and TMM induced distinct inflammatory skin lesions and TMM were depleted more slowly from skin after alemtuzumab, suggesting TMM may recirculate more slowly. In summary, human skin is protected by four functionally distinct populations of T cells, two resident and two recirculating, with differing territories of migration and distinct functional activities. PMID:25787765

Neural correlates of target selection for reaching movements in superior colliculus

PubMed Central

McPeek, Robert M.

2014-01-01

We recently demonstrated that inactivation of the primate superior colliculus (SC) causes a deficit in target selection for arm-reaching movements when the reach target is located in the inactivated field (Song JH, Rafal RD, McPeek RM. Proc Natl Acad Sci USA 108: E1433–E1440, 2011). This is consistent with the notion that the SC is part of a general-purpose target selection network beyond eye movements. To understand better the role of SC activity in reach target selection, we examined how individual SC neurons in the intermediate layers discriminate a reach target from distractors. Monkeys reached to touch a color oddball target among distractors while maintaining fixation. We found that many SC neurons robustly discriminate the goal of the reaching movement before the onset of the reach even though no saccade is made. To identify these cells in the context of conventional SC cell classification schemes, we also recorded visual, delay-period, and saccade-related responses in a delayed saccade task. On average, SC cells that discriminated the reach target from distractors showed significantly higher visual and delay-period activity than nondiscriminating cells, but there was no significant difference in saccade-related activity. Whereas a majority of SC neurons that discriminated the reach target showed significant delay-period activity, all nondiscriminating cells lacked such activity. We also found that some cells without delay-period activity did discriminate the reach target from distractors. We conclude that the majority of intermediate-layer SC cells discriminate a reach target from distractors, consistent with the idea that the SC contains a priority map used for effector-independent target selection. PMID:25505107

Pretransplantation recipient regulatory T cell suppressive function predicts delayed and slow graft function after kidney transplantation.

PubMed

Nguyen, Minh-Tri J P; Fryml, Elise; Sahakian, Sossy K; Liu, Shuqing; Michel, Rene P; Lipman, Mark L; Mucsi, Istvan; Cantarovich, Marcelo; Tchervenkov, Jean I; Paraskevas, Steven

2014-10-15

Delayed graft function (DGF) and slow graft function (SGF) are a continuous spectrum of ischemia-reperfusion-related acute kidney injury (AKI) that increases the risk for acute rejection and graft loss after kidney transplantation. Regulatory T cells (Tregs) are critical in transplant tolerance and attenuate murine AKI. In this prospective observational cohort study, we evaluated whether pretransplantation peripheral blood recipient Treg frequency and suppressive function are predictors of DGF and SGF after kidney transplantation. Deceased donor kidney transplant recipients (n=53) were divided into AKI (n=37; DGF, n=10; SGF, n=27) and immediate graft function (n=16) groups. Pretransplantation peripheral blood CD4CD25FoxP3 Treg frequency was quantified by flow cytometry. Regulatory T-cell suppressive function was measured by suppression of autologous effector T-cell proliferation by Treg in co-culture. Pretransplantation Treg suppressive function, but not frequency, was decreased in AKI recipients (P<0.01). In univariate and multivariate analyses accounting for the effects of cold ischemic time and donor age, Treg suppressive function discriminated DGF from immediate graft function recipients in multinomial logistic regression (odds ratio, 0.77; P<0.01), accurately predicted AKI in receiver operating characteristic curve (area under the curve, 0.82; P<0.01), and predicted 14-day estimated glomerular filtration rate in linear regression (P<0.01). Our results indicate that recipient peripheral blood Treg suppressive function is a potential independent pretransplantation predictor of DGF and SGF.

Changes in neural network homeostasis trigger neuropsychiatric symptoms.

PubMed

Winkelmann, Aline; Maggio, Nicola; Eller, Joanna; Caliskan, Gürsel; Semtner, Marcus; Häussler, Ute; Jüttner, René; Dugladze, Tamar; Smolinsky, Birthe; Kowalczyk, Sarah; Chronowska, Ewa; Schwarz, Günter; Rathjen, Fritz G; Rechavi, Gideon; Haas, Carola A; Kulik, Akos; Gloveli, Tengis; Heinemann, Uwe; Meier, Jochen C

2014-02-01

The mechanisms that regulate the strength of synaptic transmission and intrinsic neuronal excitability are well characterized; however, the mechanisms that promote disease-causing neural network dysfunction are poorly defined. We generated mice with targeted neuron type-specific expression of a gain-of-function variant of the neurotransmitter receptor for glycine (GlyR) that is found in hippocampectomies from patients with temporal lobe epilepsy. In this mouse model, targeted expression of gain-of-function GlyR in terminals of glutamatergic cells or in parvalbumin-positive interneurons persistently altered neural network excitability. The increased network excitability associated with gain-of-function GlyR expression in glutamatergic neurons resulted in recurrent epileptiform discharge, which provoked cognitive dysfunction and memory deficits without affecting bidirectional synaptic plasticity. In contrast, decreased network excitability due to gain-of-function GlyR expression in parvalbumin-positive interneurons resulted in an anxiety phenotype, but did not affect cognitive performance or discriminative associative memory. Our animal model unveils neuron type-specific effects on cognition, formation of discriminative associative memory, and emotional behavior in vivo. Furthermore, our data identify a presynaptic disease-causing molecular mechanism that impairs homeostatic regulation of neural network excitability and triggers neuropsychiatric symptoms.

Unique volatolomic signatures of TP53 and KRAS in lung cells

PubMed Central

Davies, M P A; Barash, O; Jeries, R; Peled, N; Ilouze, M; Hyde, R; Marcus, M W; Field, J K; Haick, H

2014-01-01

Background: Volatile organic compounds (VOCs) are potential biomarkers for cancer detection in breath, but it is unclear if they reflect specific mutations. To test this, we have compared human bronchial epithelial cell (HBEC) cell lines carrying the KRASV12 mutation, knockdown of TP53 or both with parental HBEC cells. Methods: VOC from headspace above cultured cells were collected by passive sampling and analysed by thermal desorption gas chromatography mass spectrometry (TD-GC–MS) or sensor array with discriminant factor analysis (DFA). Results: In TD-GC–MS analysis, individual compounds had limited ability to discriminate between cell lines, but by applying DFA analysis combinations of 20 VOCs successfully discriminated between all cell types (accuracies 80–100%, with leave-one-out cross validation). Sensor array detection DFA demonstrated the ability to discriminate samples based on their cell type for all comparisons with accuracies varying between 77% and 93%. Conclusions: Our results demonstrate that minimal genetic changes in bronchial airway cells lead to detectable differences in levels of specific VOCs identified by TD-GC–MS or of patterns of VOCs identified by sensor array output. From the clinical aspect, these results suggest the possibility of breath analysis for detection of minimal genetic changes for earlier diagnosis or for genetic typing of lung cancers. PMID:25051409

The tyrosine phosphatase PTPN22 discriminates weak self peptides from strong agonist TCR signals.

PubMed

Salmond, Robert J; Brownlie, Rebecca J; Morrison, Vicky L; Zamoyska, Rose

2014-09-01

T cells must be tolerant of self antigens to avoid autoimmunity but responsive to foreign antigens to provide protection against infection. We found that in both naive T cells and effector T cells, the tyrosine phosphatase PTPN22 limited signaling via the T cell antigen receptor (TCR) by weak agonists and self antigens while not impeding responses to strong agonist antigens. T cells lacking PTPN22 showed enhanced formation of conjugates with antigen-presenting cells pulsed with weak peptides, which led to activation of the T cells and their production of inflammatory cytokines. This effect was exacerbated under conditions of lymphopenia, with the formation of potent memory T cells in the absence of PTPN22. Our data address how loss-of-function PTPN22 alleles can lead to the population expansion of effector and/or memory T cells and a predisposition to human autoimmunity.

How do biological systems discriminate among physically similar ions?

PubMed

Diamond, J M

1975-10-01

This paper reviews the history of understanding how biological systems can discriminate so strikingly among physically similar ions, especially alkali cations. Appreciation of qualitative regularities ("permitted sequences") and quantitative regularities ("selectivity isotherms") in ion selectivity grew first from studies of ion exchangers and glass electrodes, then of biological systems such as enzymes and cell membranes, and most recently of lipid bilayers doped with model pores and carriers. Discrimination of ions depends on both electrostatic and steric forces. "Black-box" studies on intact biological membranes have in some cases yielded molecular clues to the structure of the actual biological pores and carriers. Major current problems involve the extraction of these molecules; how to do it, what to do when it is achieved, and how (and if) it is relevant to the central problems of membrane function. Further advances are expected soon from studies of rate barriers within membranes, of voltage-dependent ("excitable") conducting channels, and of increasingly complex model systems and biological membranes.

Molecular basis of ancestral vertebrate electroreception

PubMed Central

Bellono, Nicholas W.; Leitch, Duncan B.; Julius, David

2017-01-01

Elasmobranch fishes, including sharks, rays, and skates, use specialized electrosensory organs called Ampullae of Lorenzini to detect extremely small changes in environmental electric fields. Electrosensory cells within these ampullae are able to discriminate and respond to minute changes in environmental voltage gradients through an as-yet unknown mechanism. Here we show that the voltage-gated calcium channel CaV1.3 and big conductance calcium-activated potassium (BK) channel are preferentially expressed by electrosensory cells in little skate (Leucoraja erinacea) and functionally couple to mediate electrosensory cell membrane voltage oscillations, which are important in the detection of specific, weak electrical signals. Both channels exhibit unique properties compared with their mammalian orthologues to support electrosensory functions: structural adaptations in CaV1.3 mediate a low voltage threshold for activation, while alterations in BK support specifically tuned voltage oscillations. These findings reveal a molecular basis of electroreception and demonstrate how discrete evolutionary changes in ion channel structure facilitate sensory adaptation. PMID:28264196

Clathrin-independent pathways do not contribute significantly to endocytic flux.

PubMed

Bitsikas, Vassilis; Corrêa, Ivan R; Nichols, Benjamin J

2014-09-17

Several different endocytic pathways have been proposed to function in mammalian cells. Clathrin-coated pits are well defined, but the identity, mechanism and function of alternative pathways have been controversial. Here we apply universal chemical labelling of plasma membrane proteins to define all primary endocytic vesicles, and labelling of specific proteins with a reducible SNAP-tag substrate. These approaches provide high temporal resolution and stringent discrimination between surface-connected and intracellular membranes. We find that at least 95% of the earliest detectable endocytic vesicles arise from clathrin-coated pits. GPI-anchored proteins, candidate cargoes for alternate pathways, are also found to enter the cell predominantly via coated pits. Experiments employing a mutated clathrin adaptor reveal distinct mechanisms for sorting into coated pits, and thereby explain differential effects on the uptake of transferrin and GPI-anchored proteins. These data call for a revision of models for the activity and diversity of endocytic pathways in mammalian cells.

Differential gene expression profiles of peripheral blood mononuclear cells in childhood asthma.

PubMed

Kong, Qian; Li, Wen-Jing; Huang, Hua-Rong; Zhong, Ying-Qiang; Fang, Jian-Pei

2015-05-01

Asthma is a common childhood disease with strong genetic components. This study compared whole-genome expression differences between asthmatic young children and healthy controls to identify gene signatures of childhood asthma. Total RNA extracted from peripheral blood mononuclear cells (PBMC) was subjected to microarray analysis. QRT-PCR was performed to verify the microarray results. Classification and functional characterization of differential genes were illustrated by hierarchical clustering and gene ontology analysis. Multiple logistic regression (MLR) analysis, receiver operating characteristic (ROC) curve analysis, and discriminate power were used to scan asthma-specific diagnostic markers. For fold-change>2 and p < 0.05, there were 758 named differential genes. The results of QRT-PCR confirmed successfully the array data. Hierarchical clustering divided 29 highly possible genes into seven categories and the genes in the same cluster were likely to possess similar expression patterns or functions. Gene ontology analysis presented that differential genes primarily enriched in immune response, response to stress or stimulus, and regulation of apoptosis in biological process. MLR and ROC curve analysis revealed that the combination of ADAM33, Smad7, and LIGHT possessed excellent discriminating power. The combination of ADAM33, Smad7, and LIGHT would be a reliable and useful childhood asthma model for prediction and diagnosis.

Seasonal Plasticity of Precise Spike Timing in the Avian Auditory System

PubMed Central

Sen, Kamal; Rubel, Edwin W; Brenowitz, Eliot A.

2015-01-01

Vertebrate audition is a dynamic process, capable of exhibiting both short- and long-term adaptations to varying listening conditions. Precise spike timing has long been known to play an important role in auditory encoding, but its role in sensory plasticity remains largely unexplored. We addressed this issue in Gambel's white-crowned sparrow (Zonotrichia leucophrys gambelii), a songbird that shows pronounced seasonal fluctuations in circulating levels of sex-steroid hormones, which are known to be potent neuromodulators of auditory function. We recorded extracellular single-unit activity in the auditory forebrain of males and females under different breeding conditions and used a computational approach to explore two potential strategies for the neural discrimination of sound level: one based on spike counts and one based on spike timing reliability. We report that breeding condition has robust sex-specific effects on spike timing. Specifically, in females, breeding condition increases the proportion of cells that rely solely on spike timing information and increases the temporal resolution required for optimal intensity encoding. Furthermore, in a functionally distinct subset of cells that are particularly well suited for amplitude encoding, female breeding condition enhances spike timing-based discrimination accuracy. No effects of breeding condition were observed in males. Our results suggest that high-resolution temporal discharge patterns may provide a plastic neural substrate for sensory coding. PMID:25716843

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

Brousseau, P.; Fugere, N.; Coderre, D.

Immunotoxic effects of environmental exposure to chemical contaminants can be evaluated by monitoring cellular and functional parameters of the immune system of sentinel species. In this scope, the earthworm may represent a relevant sentinel species to determine the level of toxicity linked to soil contaminants or to test the efficacy of remediation protocols. In this work, coelomocytes were incubated in vitro for 18 hours with mercury, cadmium, zinc or lead at concentrations ranging from 10{sup {minus}9} to 10{sup {minus}4}M. The analysis of phagocytosis by flow cytometry revealed that this natural response was impaired at non cytotoxic concentrations of mercury, cadmiummore » and zinc. Moreover, the analysis of cells obtained from coelomic fluid, based on the combination of low angle forward scatter (FSC) and side scatter (SSC) allowed to discriminate between two distinct populations of coelomocytes. With the use of fluorescent probes, such as carboxyfluorescin diacetate (CFDA), dichlorofluorescin diacetate (DCFDA) and chloromethyl fluorescin diacetate (CFDA), to study the esterase activity and Fluo-3 to measure free cytoplasmic calcium, the results showed that the first discrimination between the two populations of cells based on size and complexity could be further accentuated on the basis of their metabolic activities. In summary, the data make very attractive the use of flow cytometry to study cellular and functional parameters of the earthworm.« less

All-In-One: Advanced preparation of Human Parenchymal and Non-Parenchymal Liver Cells

PubMed Central

Werner, Melanie; Driftmann, Sabrina; Kleinehr, Kathrin; Kaiser, Gernot M.; Mathé, Zotlan; Treckmann, Juergen-Walter; Paul, Andreas; Skibbe, Kathrin; Timm, Joerg; Canbay, Ali; Gerken, Guido; Schlaak, Joerg F.; Broering, Ruth

2015-01-01

Background & Aims Liver cells are key players in innate immunity. Thus, studying primary isolated liver cells is necessary for determining their role in liver physiology and pathophysiology. In particular, the quantity and quality of isolated cells are crucial to their function. Our aim was to isolate a large quantity of high-quality human parenchymal and non-parenchymal cells from a single liver specimen. Methods Hepatocytes, Kupffer cells, liver sinusoidal endothelial cells, and stellate cells were isolated from liver tissues by collagenase perfusion in combination with low-speed centrifugation, density gradient centrifugation, and magnetic-activated cell sorting. The purity and functionality of cultured cell populations were controlled by determining their morphology, discriminative cell marker expression, and functional activity. Results Cell preparation yielded the following cell counts per gram of liver tissue: 2.0±0.4×107 hepatocytes, 1.8±0.5×106 Kupffer cells, 4.3±1.9×105 liver sinusoidal endothelial cells, and 3.2±0.5×105 stellate cells. Hepatocytes were identified by albumin (95.5±1.7%) and exhibited time-dependent activity of cytochrome P450 enzymes. Kupffer cells expressed CD68 (94.5±1.2%) and exhibited phagocytic activity, as determined with 1μm latex beads. Endothelial cells were CD146+ (97.8±1.1%) and exhibited efficient uptake of acetylated low-density lipoprotein. Hepatic stellate cells were identified by the expression of α-smooth muscle actin (97.1±1.5%). These cells further exhibited retinol (vitamin A)-mediated autofluorescence. Conclusions Our isolation procedure for primary parenchymal and non-parenchymal liver cells resulted in cell populations of high purity and quality, with retained physiological functionality in vitro. Thus, this system may provide a valuable tool for determining liver function and disease. PMID:26407160

Assessment of contrast gain signature in inferred magnocellular and parvocellular pathways in patients with glaucoma.

PubMed

Sun, Hao; Swanson, William H; Arvidson, Brian; Dul, Mitchell W

2008-11-01

Contrast gain signatures of inferred magnocellular and parvocellular postreceptoral pathways were assessed for patients with glaucoma using a contrast discrimination paradigm developed by Pokorny and Smith. The potential causes for changes in contrast gain signature were investigated using model simulations of ganglion cell contrast responses. Foveal contrast discrimination thresholds were measured with a pedestal-Delta-pedestal paradigm developed by Pokorny and Smith [Pokorny, J., & Smith, V. C. (1997). Psychophysical signatures associated with magnocellular and parvocellular pathway contrast gain. Journal of the Optical Society of America A, 14(9), 2477-2486]. Stimuli were 27 ms luminance increments superimposed on 227 ms pulsed Delta-pedestals. Contrast thresholds and contrast gain signatures mediated by the inferred magnocellular (MC) and parvocellular (PC) pathways were assessed using linear fits to contrast discrimination thresholds at either lower or higher Delta-pedestal contrasts, respectively. Twenty-seven patients with glaucoma were tested, as well as 16 age-similar control subjects free of eye disease. Contrast sensitivity and contrast gain signature mediated by the inferred MC pathway were lower for the glaucoma group, and reduced contrast gain signature was correlated with reduced contrast sensitivity (r(2)=45%, p<.0005). These two parameters mediated by the inferred PC pathway were little affected for the glaucoma group. Model simulations suggest that the reduced contrast sensitivity and contrast gain signature were consistent with the hypothesis that reduced MC ganglion cell dendritic complexity can lead to reduced effective retinal illuminance, and hence increased semi-saturation contrast of the ganglion cell contrast response functions. The contrast sensitivity and contrast gain signature of the inferred MC pathway were reduced in patients with glaucoma. The results were consistent with a model of ganglion cell dysfunction due to reduced synaptic density.

Aberrant functional connectivity for diagnosis of major depressive disorder: a discriminant analysis.

PubMed

Cao, Longlong; Guo, Shuixia; Xue, Zhimin; Hu, Yong; Liu, Haihong; Mwansisya, Tumbwene E; Pu, Weidan; Yang, Bo; Liu, Chang; Feng, Jianfeng; Chen, Eric Y H; Liu, Zhening

2014-02-01

Aberrant brain functional connectivity patterns have been reported in major depressive disorder (MDD). It is unknown whether they can be used in discriminant analysis for diagnosis of MDD. In the present study we examined the efficiency of discriminant analysis of MDD by individualized computer-assisted diagnosis. Based on resting-state functional magnetic resonance imaging data, a new approach was adopted to investigate functional connectivity changes in 39 MDD patients and 37 well-matched healthy controls. By using the proposed feature selection method, we identified significant altered functional connections in patients. They were subsequently applied to our analysis as discriminant features using a support vector machine classification method. Furthermore, the relative contribution of functional connectivity was estimated. After subset selection of high-dimension features, the support vector machine classifier reached up to approximately 84% with leave-one-out training during the discrimination process. Through summarizing the classification contribution of functional connectivities, we obtained four obvious contribution modules: inferior orbitofrontal module, supramarginal gyrus module, inferior parietal lobule-posterior cingulated gyrus module and middle temporal gyrus-inferior temporal gyrus module. The experimental results demonstrated that the proposed method is effective in discriminating MDD patients from healthy controls. Functional connectivities might be useful as new biomarkers to assist clinicians in computer auxiliary diagnosis of MDD. © 2013 The Authors. Psychiatry and Clinical Neurosciences © 2013 Japanese Society of Psychiatry and Neurology.

Label-free separation of human embryonic stem cells and their differentiating progenies by phasor fluorescence lifetime microscopy

NASA Astrophysics Data System (ADS)

Stringari, Chiara; Sierra, Robert; Donovan, Peter J.; Gratton, Enrico

2012-04-01

We develop a label-free optical technique to image and discriminate undifferentiated human embryonic stem cells (hESCs) from their differentiating progenies in vitro. Using intrinsic cellular fluorophores, we perform fluorescence lifetime microscopy (FLIM) and phasor analysis to obtain hESC metabolic signatures. We identify two optical biomarkers to define the differentiation status of hESCs: Nicotinamide adenine dinucleotide (NADH) and lipid droplet-associated granules (LDAGs). These granules have a unique lifetime signature and could be formed by the interaction of reactive oxygen species and unsaturated metabolic precursor that are known to be abundant in hESC. Changes in the relative concentrations of these two intrinsic biomarkers allow for the discrimination of undifferentiated hESCs from differentiating hESCs. During early hESC differentiation we show that NADH concentrations increase, while the concentration of LDAGs decrease. These results are in agreement with a decrease in oxidative phosphorylation rate. Single-cell phasor FLIM signatures reveal an increased heterogeneity in the metabolic states of differentiating H9 and H1 hESC colonies. This technique is a promising noninvasive tool to monitor hESC metabolism during differentiation, which can have applications in high throughput analysis, drug screening, functional metabolomics and induced pluripotent stem cell generation.

Melanopsin-based brightness discrimination in mice and humans.

PubMed

Brown, Timothy M; Tsujimura, Sei-Ichi; Allen, Annette E; Wynne, Jonathan; Bedford, Robert; Vickery, Graham; Vugler, Anthony; Lucas, Robert J

2012-06-19

Photoreception in the mammalian retina is not restricted to rods and cones but extends to a small number of intrinsically photoreceptive retinal ganglion cells (ipRGCs), expressing the photopigment melanopsin. ipRGCs are known to support various accessory visual functions including circadian photoentrainment and pupillary reflexes. However, despite anatomical and physiological evidence that they contribute to the thalamocortical visual projection, no aspect of visual discrimination has been shown to rely upon ipRGCs. Based on their currently known roles, we hypothesized that ipRGCs may contribute to distinguishing brightness. This percept is related to an object's luminance-a photometric measure of light intensity relevant for cone photoreceptors. However, the perceived brightness of different sources is not always predicted by their respective luminance. Here, we used parallel behavioral and electrophysiological experiments to first show that melanopsin contributes to brightness discrimination in both retinally degenerate and fully sighted mice. We continued to use comparable paradigms in psychophysical experiments to provide evidence for a similar role in healthy human subjects. These data represent the first direct evidence that an aspect of visual discrimination in normally sighted subjects can be supported by inner retinal photoreceptors. Copyright © 2012 Elsevier Ltd. All rights reserved.

Heparan Sulfates Support Pyramidal Cell Excitability, Synaptic Plasticity, and Context Discrimination

PubMed Central

Minge, Daniel; Senkov, Oleg; Kaushik, Rahul; Herde, Michel K.; Tikhobrazova, Olga; Wulff, Andreas B.; Mironov, Andrey; van Kuppevelt, Toin H.; Oosterhof, Arie; Kochlamazashvili, Gaga

2017-01-01

Abstract Heparan sulfate (HS) proteoglycans represent a major component of the extracellular matrix and are critical for brain development. However, their function in the mature brain remains to be characterized. Here, acute enzymatic digestion of HS side chains was used to uncover how HSs support hippocampal function in vitro and in vivo. We found that long-term potentiation (LTP) of synaptic transmission at CA3–CA1 Schaffer collateral synapses was impaired after removal of highly sulfated HSs with heparinase 1. This reduction was associated with decreased Ca2+ influx during LTP induction, which was the consequence of a reduced excitability of CA1 pyramidal neurons. At the subcellular level, heparinase treatment resulted in reorganization of the distal axon initial segment, as detected by a reduction in ankyrin G expression. In vivo, digestion of HSs impaired context discrimination in a fear conditioning paradigm and oscillatory network activity in the low theta band after fear conditioning. Thus, HSs maintain neuronal excitability and, as a consequence, support synaptic plasticity and learning. PMID:28119345

Separability of stimulus parameter encoding by on-off directionally selective rabbit retinal ganglion cells

PubMed Central

Nowak, Przemyslaw; Dobbins, Allan C.; Gawne, Timothy J.; Grzywacz, Norberto M.

2011-01-01

The ganglion cell output of the retina constitutes a bottleneck in sensory processing in that ganglion cells must encode multiple stimulus parameters in their responses. Here we investigate encoding strategies of On-Off directionally selective retinal ganglion cells (On-Off DS RGCs) in rabbits, a class of cells dedicated to representing motion. The exquisite axial discrimination of these cells to preferred vs. null direction motion is well documented: it is invariant with respect to speed, contrast, spatial configuration, spatial frequency, and motion extent. However, these cells have broad direction tuning curves and their responses also vary as a function of other parameters such as speed and contrast. In this study, we examined whether the variation in responses across multiple stimulus parameters is systematic, that is the same for all cells, and separable, such that the response to a stimulus is a product of the effects of each stimulus parameter alone. We extracellularly recorded single On-Off DS RGCs in a superfused eyecup preparation while stimulating them with moving bars. We found that spike count responses of these cells scaled as independent functions of direction, speed, and luminance. Moreover, the speed and luminance functions were common across the whole sample of cells. Based on these findings, we developed a model that accurately predicted responses of On-Off DS RGCs as products of separable functions of direction, speed, and luminance (r = 0.98; P < 0.0001). Such a multiplicatively separable encoding strategy may simplify the decoding of these cells' outputs by the higher visual centers. PMID:21325684

Discrimination of Isomers of Released N- and O-Glycans Using Diagnostic Product Ions in Negative Ion PGC-LC-ESI-MS/MS

NASA Astrophysics Data System (ADS)

Ashwood, Christopher; Lin, Chi-Hung; Thaysen-Andersen, Morten; Packer, Nicolle H.

2018-03-01

Profiling cellular protein glycosylation is challenging due to the presence of highly similar glycan structures that play diverse roles in cellular physiology. As the anomericity and the exact linkage type of a single glycosidic bond can influence glycan function, there is a demand for improved and automated methods to confirm detailed structural features and to discriminate between structurally similar isomers, overcoming a significant bottleneck in the analysis of data generated by glycomics experiments. We used porous graphitized carbon-LC-ESI-MS/MS to separate and detect released N- and O-glycan isomers from mammalian model glycoproteins using negative mode resonance activation CID-MS/MS. By interrogating similar fragment spectra from closely related glycan isomers that differ only in arm position and sialyl linkage, product fragment ions for discrimination between these features were discovered. Using the Skyline software, at least two diagnostic fragment ions of high specificity were validated for automated discrimination of sialylation and arm position in N-glycan structures, and sialylation in O-glycan structures, complementing existing structural diagnostic ions. These diagnostic ions were shown to be useful for isomer discrimination using both linear and 3D ion trap mass spectrometers when analyzing complex glycan mixtures from cell lysates. Skyline was found to serve as a useful tool for automated assessment of glycan isomer discrimination. This platform-independent workflow can potentially be extended to automate the characterization and quantitation of other challenging glycan isomers. [Figure not available: see fulltext.

Multimodal discrimination of immune cells using a combination of Raman spectroscopy and digital holographic microscopy

NASA Astrophysics Data System (ADS)

McReynolds, Naomi; Cooke, Fiona G. M.; Chen, Mingzhou; Powis, Simon J.; Dholakia, Kishan

2017-03-01

The ability to identify and characterise individual cells of the immune system under label-free conditions would be a significant advantage in biomedical and clinical studies where untouched and unmodified cells are required. We present a multi-modal system capable of simultaneously acquiring both single point Raman spectra and digital holographic images of single cells. We use this combined approach to identify and discriminate between immune cell populations CD4+ T cells, B cells and monocytes. We investigate several approaches to interpret the phase images including signal intensity histograms and texture analysis. Both modalities are independently able to discriminate between cell subsets and dual-modality may therefore be used a means for validation. We demonstrate here sensitivities achieved in the range of 86.8% to 100%, and specificities in the range of 85.4% to 100%. Additionally each modality provides information not available from the other providing both a molecular and a morphological signature of each cell.

Bacterial accumulation in viscosity gradients

NASA Astrophysics Data System (ADS)

Waisbord, Nicolas; Guasto, Jeffrey

2016-11-01

Cell motility is greatly modified by fluid rheology. In particular, the physical environments in which cells function, are often characterized by gradients of viscous biopolymers, such as mucus and extracellular matrix, which impact processes ranging from reproduction to digestion to biofilm formation. To understand how spatial heterogeneity of fluid rheology affects the motility and transport of swimming cells, we use hydrogel microfluidic devices to generate viscosity gradients in a simple, polymeric, Newtonian fluid. Using video microscopy, we characterize the random walk motility patterns of model bacteria (Bacillus subtilis), showing that both wild-type ('run-and-tumble') cells and smooth-swimming mutants accumulate in the viscous region of the fluid. Through statistical analysis of individual cell trajectories and body kinematics in both homogeneous and heterogeneous viscous environments, we discriminate passive, physical effects from active sensing processes to explain the observed cell accumulation at the ensemble level.

Tuberculin-Specific T Cells Are Reduced in Active Pulmonary Tuberculosis Compared to LTBI or Status Post BCG Vaccination

PubMed Central

Streitz, Mathias; Fuhrmann, Stephan; Powell, Fiona; Quassem, Ali; Nomura, Laurel; Maecker, Holden; Martus, Peter; Volk, Hans-Dieter

2011-01-01

Functional characteristics of tuberculosis (TB)–specific CD4 T cells were studied in clinically active pulmonary TB (n = 21) and high TB exposure including LTBI (n = 17). Following tuberculin stimulation, activated CD4 T cells were identified by flow-cytometry (CD154 up-regulation, degranulation, interferon γ [IFN-γ], tumor necrosis factor α [TNF-α], and interleukin 2 [IL-2\\ production). Interestingly, CD154 up-regulation accounted for ∼80% of activated CD4 T cells in the active TB group but just 40% in the controls, whereas IFN-γ accounted for only ∼50% of activated cells in each group. The frequencies of CD4 T cells displaying at least 1 activation marker discriminated better between the groups than those displaying degranulation or IFN-γ production alone. PMID:21186260

Laser scanning cytometry (LCS) allows detailed analysis of the cell cycle in PI stained human fibroblasts (TIG-7).

PubMed

Kawasaki, M; Sasaki, K; Satoh, T; Kurose, A; Kamada, T; Furuya, T; Murakami, T; Todoroki, T

1997-01-01

We have demonstrated a method for the in situ determination of the cell cycle phases of TIG-7 fibroblasts using a laser scanning cytometer (LSC) which has not only a function equivalent to flow cytometry (FCM) but also has a capability unique in itself. LSC allows a more detailed analysis of the cell cycle in cells stained with propidium iodide (PI) than FCM. With LSC it is possible to discriminate between mitotic cells and G2 cells, between post-mitotic cells and G1 cells, and between quiescent cells and cycling cells in a PI fluorescence peak (chromatin condensation) vs. fluorescence value (DNA content) cytogram for cells stained with PI. These were amply confirmed by experiments using colcemid and adriamycin. We were able to identify at least six cell subpopulations for PI stained cells using LSC; namely G1, S, G2, M, postmitotic and quiescent cell populations. LSC analysis facilitates the monitoring of effects of drugs on the cell cycle.

Label-free haemogram using wavelength modulated Raman spectroscopy for identifying immune-cell subset

NASA Astrophysics Data System (ADS)

Ashok, Praveen C.; Praveen, Bavishna B.; Campbell, Elaine C.; Dholakia, Kishan; Powis, Simon J.

2014-03-01

Leucocytes in the blood of mammals form a powerful protective system against a wide range of dangerous pathogens. There are several types of immune cells that has specific role in the whole immune system. The number and type of immune cells alter in the disease state and identifying the type of immune cell provides information about a person's state of health. There are several immune cell subsets that are essentially morphologically identical and require external labeling to enable discrimination. Here we demonstrate the feasibility of using Wavelength Modulated Raman Spectroscopy (WMRS) with suitable machine learning algorithms as a label-free method to distinguish between different closely lying immune cell subset. Principal Component Analysis (PCA) was performed on WMRS data from single cells, obtained using confocal Raman microscopy for feature reduction, followed by Support Vector Machine (SVM) for binary discrimination of various cell subset, which yielded an accuracy >85%. The method was successful in discriminating between untouched and unfixed purified populations of CD4+CD3+ and CD8+CD3+ T lymphocyte subsets, and CD56+CD3- natural killer cells with a high degree of specificity. It was also proved sensitive enough to identify unique Raman signatures that allow clear discrimination between dendritic cell subsets, comprising CD303+CD45+ plasmacytoid and CD1c+CD141+ myeloid dendritic cells. The results of this study clearly show that WMRS is highly sensitive and can distinguish between cell types that are morphologically identical.

Caregiver Experiences of Discrimination and African American Adolescents' Psychological Health over Time

ERIC Educational Resources Information Center

Ford, Kahlil R.; Hurd, Noelle M.; Jagers, Robert J.; Sellers, Robert M.

2013-01-01

The present study examined the effect of caregivers' experiences of racial discrimination on their adolescent children's psychological functioning among a sample of 264 African American dyads. Potential relations between caregiver discrimination experiences and a number of indicators of adolescents' (aged 12-17) psychological functioning over time…

Discriminating Among Probability Weighting Functions Using Adaptive Design Optimization

PubMed Central

Cavagnaro, Daniel R.; Pitt, Mark A.; Gonzalez, Richard; Myung, Jay I.

2014-01-01

Probability weighting functions relate objective probabilities and their subjective weights, and play a central role in modeling choices under risk within cumulative prospect theory. While several different parametric forms have been proposed, their qualitative similarities make it challenging to discriminate among them empirically. In this paper, we use both simulation and choice experiments to investigate the extent to which different parametric forms of the probability weighting function can be discriminated using adaptive design optimization, a computer-based methodology that identifies and exploits model differences for the purpose of model discrimination. The simulation experiments show that the correct (data-generating) form can be conclusively discriminated from its competitors. The results of an empirical experiment reveal heterogeneity between participants in terms of the functional form, with two models (Prelec-2, Linear in Log Odds) emerging as the most common best-fitting models. The findings shed light on assumptions underlying these models. PMID:24453406

Statistical classification techniques for engineering and climatic data samples

NASA Technical Reports Server (NTRS)

Temple, E. C.; Shipman, J. R.

1981-01-01

Fisher's sample linear discriminant function is modified through an appropriate alteration of the common sample variance-covariance matrix. The alteration consists of adding nonnegative values to the eigenvalues of the sample variance covariance matrix. The desired results of this modification is to increase the number of correct classifications by the new linear discriminant function over Fisher's function. This study is limited to the two-group discriminant problem.

FUNCTIONAL LIMITATION AND DEPRESSIVE SYMPTOMATOLOGY: CONSIDERING PERCEIVED STIGMA AND DISCRIMINATION WITHIN A STRESS AND COPING FRAMEWORK

PubMed Central

Brown, Robyn Lewis

2016-01-01

This study examines whether perceived stigma and discrimination moderate the associations between functional limitation, psychosocial coping resources, and depressive symptoms among people with physical disabilities. Using two waves of data from a large community study including a representative sample of persons with physical disabilities (N=417), an SEM-based moderated mediation analysis was performed. Mediation tests demonstrate that mastery significantly mediates the association between functional limitation and depressive symptoms over the study period. Moderated mediation tests reveal that the linkage between functional limitation and mastery varies as a function of perceived stigma and experiences of major discrimination and day-to-day discrimination, however. The implications of these findings are discussed in the context of the stress and coping literature. PMID:28497112

Classification of debtor credit status and determination amount of credit risk by using linier discriminant function

NASA Astrophysics Data System (ADS)

Aidi, Muhammad Nur; Sari, Resty Indah

2012-05-01

A decision of credit that given by bank or another creditur must have a risk and it called credit risk. Credit risk is an investor's risk of loss arising from a borrower who does not make payments as promised. The substantial of credit risk can lead to losses for the banks and the debtor. To minimize this problem need a further study to identify a potential new customer before the decision given. Identification of debtor can using various approaches analysis, one of them is by using discriminant analysis. Discriminant analysis in this study are used to classify whether belonging to the debtor's good credit or bad credit. The result of this study are two discriminant functions that can identify new debtor. Before step built the discriminant function, selection of explanatory variables should be done. Purpose of selection independent variable is to choose the variable that can discriminate the group maximally. Selection variables in this study using different test, for categoric variable selection of variable using proportion chi-square test, and stepwise discriminant for numeric variable. The result of this study are two discriminant functions that can identify new debtor. The selected variables that can discriminating two groups of debtor maximally are status of existing checking account, credit history, credit amount, installment rate in percentage of disposable income, sex, age in year, other installment plans, and number of people being liable to provide maintenance. This classification produce a classification accuracy rate is good enough, that is equal to 74,70%. Debtor classification using discriminant analysis has risk level that is small enough, and it ranged beetwen 14,992% and 17,608%. Based on that credit risk rate, using discriminant analysis on the classification of credit status can be used effectively.

Trained Musical Performers' and Musically Untrained College Students' Ability to Discriminate Music Instrument Timbre as a Function of Duration.

NASA Astrophysics Data System (ADS)

Johnston, Dennis Alan

The purpose of this study was to investigate the ability of trained musicians and musically untrained college students to discriminate music instrument timbre as a function of duration. Specific factors investigated were the thresholds for timbre discrimination as a function of duration, musical ensemble participation as training, and the relative discrimination abilities of vocalists and instrumentalists. The subjects (N = 126) were volunteer college students from intact classes from various disciplines separated into musically untrained college students (N = 43) who had not participated in musical ensembles and trained musicians (N = 83) who had. The musicians were further divided into instrumentalists (N = 51) and vocalists (N = 32). The Method of Constant Stimuli, using a same-different response procedure with 120 randomized, counterbalanced timbre pairs comprised of trumpet, clarinet, or violin, presented in durations of 20 to 100 milliseconds in a sequence of pitches, in two blocks was used for data collection. Complete, complex musical timbres were recorded digitally and presented in a sequence of changing pitches to more closely approximate an actual music listening experience. Under the conditions of this study, it can be concluded that the threshold for timbre discrimination as a function of duration is at or below 20 ms. Even though trained musicians tended to discriminate timbre better than musically untrained college students, musicians cannot discriminate timbre significantly better then those subjects who have not participated in musical ensembles. Additionally, instrumentalists tended to discriminate timbre better than vocalists, but the discrimination is not significantly different. Recommendations for further research include suggestions for a timbre discrimination measurement tool that takes into consideration the multidimensionality of timbre and the relationship of timbre discrimination to timbre source, duration, pitch, and loudness.

Characterizing populations and searching for diagnostics via elastic registration of MRI images

NASA Astrophysics Data System (ADS)

Pettey, David; Gee, James C.

2001-07-01

Given image data from two distinct populations and a family of functions, we find the scalar discriminant function which best discriminates between the populations. The goals are two-fold: first, to construct a discriminant function which can accurately and reliably classify subjects via the image data. Second, the best discriminant allows us to see which features in the images distinguish between the populations; these features can guide us to finding characteristic differences between the two groups even if these differences are not sufficient to perform classification. We apply our method to mid-sagittal MRI sections of the corpus callosum from 34 males and 52 females. While we are not certain of the ability of the derived discriminant function to perform sex classification, we find that regions in the anterior of the corpus callosum do appear to be more important for the discriminant function than other regions. This indicates there may be significant differences in the relative size of the splenium in males and females, as has been reported elsewhere. More notably, we applied previous methods which support this view on our larger data set, but found that these methods no longer show statistically significant differences between the male and female splenium.

Substrate stiffness governs the initiation of B cell activation by the concerted signaling of PKCβ and focal adhesion kinase

PubMed Central

Shaheen, Samina; Wan, Zhengpeng; Li, Zongyu; Chau, Alicia; Li, Xinxin; Zhang, Shaosen; Liu, Yang; Yi, Junyang; Zeng, Yingyue; Wang, Jing; Chen, Xiangjun; Xu, Liling; Chen, Wei; Wang, Fei; Lu, Yun; Zheng, Wenjie; Shi, Yan; Sun, Xiaolin; Li, Zhanguo; Xiong, Chunyang; Liu, Wanli

2017-01-01

The mechanosensing ability of lymphocytes regulates their activation in response to antigen stimulation, but the underlying mechanism remains unexplored. Here, we report that B cell mechanosensing-governed activation requires BCR signaling molecules. PMA-induced activation of PKCβ can bypass the Btk and PLC-γ2 signaling molecules that are usually required for B cells to discriminate substrate stiffness. Instead, PKCβ-dependent activation of FAK is required, leading to FAK-mediated potentiation of B cell spreading and adhesion responses. FAK inactivation or deficiency impaired B cell discrimination of substrate stiffness. Conversely, adhesion molecules greatly enhanced this capability of B cells. Lastly, B cells derived from rheumatoid arthritis (RA) patients exhibited an altered BCR response to substrate stiffness in comparison with healthy controls. These results provide a molecular explanation of how initiation of B cell activation discriminates substrate stiffness through a PKCβ-mediated FAK activation dependent manner. DOI: http://dx.doi.org/10.7554/eLife.23060.001 PMID:28755662

Heuristics to Facilitate Understanding of Discriminant Analysis.

ERIC Educational Resources Information Center

Van Epps, Pamela D.

This paper discusses the principles underlying discriminant analysis and constructs a simulated data set to illustrate its methods. Discriminant analysis is a multivariate technique for identifying the best combination of variables to maximally discriminate between groups. Discriminant functions are established on existing groups and used to…

Toward improving fine needle aspiration cytology by applying Raman microspectroscopy

NASA Astrophysics Data System (ADS)

Becker-Putsche, Melanie; Bocklitz, Thomas; Clement, Joachim; Rösch, Petra; Popp, Jürgen

2013-04-01

Medical diagnosis of biopsies performed by fine needle aspiration has to be very reliable. Therefore, pathologists/cytologists need additional biochemical information on single cancer cells for an accurate diagnosis. Accordingly, we applied three different classification models for discriminating various features of six breast cancer cell lines by analyzing Raman microspectroscopic data. The statistical evaluations are implemented by linear discriminant analysis (LDA) and support vector machines (SVM). For the first model, a total of 61,580 Raman spectra from 110 single cells are discriminated at the cell-line level with an accuracy of 99.52% using an SVM. The LDA classification based on Raman data achieved an accuracy of 94.04% by discriminating cell lines by their origin (solid tumor versus pleural effusion). In the third model, Raman cell spectra are classified by their cancer subtypes. LDA results show an accuracy of 97.45% and specificities of 97.78%, 99.11%, and 98.97% for the subtypes basal-like, HER2+/ER-, and luminal, respectively. These subtypes are confirmed by gene expression patterns, which are important prognostic features in diagnosis. This work shows the applicability of Raman spectroscopy and statistical data handling in analyzing cancer-relevant biochemical information for advanced medical diagnosis on the single-cell level.

Frequency discriminator/phase detector

NASA Technical Reports Server (NTRS)

Crow, R. B.

1974-01-01

Circuit provides dual function of frequency discriminator/phase detector which reduces frequency acquisition time without adding to circuit complexity. Both frequency discriminators, in evaluated frequency discriminator/phase detector circuits, are effective two decades above and below center frequency.

Quantifying small molecule phenotypic effects using mitochondrial morpho-functional fingerprinting and machine learning.

PubMed

Blanchet, Lionel; Smeitink, Jan A M; van Emst-de Vries, Sjenet E; Vogels, Caroline; Pellegrini, Mina; Jonckheere, An I; Rodenburg, Richard J T; Buydens, Lutgarde M C; Beyrath, Julien; Willems, Peter H G M; Koopman, Werner J H

2015-01-26

In primary fibroblasts from Leigh Syndrome (LS) patients, isolated mitochondrial complex I deficiency is associated with increased reactive oxygen species levels and mitochondrial morpho-functional changes. Empirical evidence suggests these aberrations constitute linked therapeutic targets for small chemical molecules. However, the latter generally induce multiple subtle effects, meaning that in vitro potency analysis or single-parameter high-throughput cell screening are of limited use to identify these molecules. We combine automated image quantification and artificial intelligence to discriminate between primary fibroblasts of a healthy individual and a LS patient based upon their mitochondrial morpho-functional phenotype. We then evaluate the effects of newly developed Trolox variants in LS patient cells. This revealed that Trolox ornithylamide hydrochloride best counterbalanced mitochondrial morpho-functional aberrations, effectively scavenged ROS and increased the maximal activity of mitochondrial complexes I, IV and citrate synthase. Our results suggest that Trolox-derived antioxidants are promising candidates in therapy development for human mitochondrial disorders.

Quantifying small molecule phenotypic effects using mitochondrial morpho-functional fingerprinting and machine learning

NASA Astrophysics Data System (ADS)

Blanchet, Lionel; Smeitink, Jan A. M.; van Emst-de Vries, Sjenet E.; Vogels, Caroline; Pellegrini, Mina; Jonckheere, An I.; Rodenburg, Richard J. T.; Buydens, Lutgarde M. C.; Beyrath, Julien; Willems, Peter H. G. M.; Koopman, Werner J. H.

2015-01-01

In primary fibroblasts from Leigh Syndrome (LS) patients, isolated mitochondrial complex I deficiency is associated with increased reactive oxygen species levels and mitochondrial morpho-functional changes. Empirical evidence suggests these aberrations constitute linked therapeutic targets for small chemical molecules. However, the latter generally induce multiple subtle effects, meaning that in vitro potency analysis or single-parameter high-throughput cell screening are of limited use to identify these molecules. We combine automated image quantification and artificial intelligence to discriminate between primary fibroblasts of a healthy individual and a LS patient based upon their mitochondrial morpho-functional phenotype. We then evaluate the effects of newly developed Trolox variants in LS patient cells. This revealed that Trolox ornithylamide hydrochloride best counterbalanced mitochondrial morpho-functional aberrations, effectively scavenged ROS and increased the maximal activity of mitochondrial complexes I, IV and citrate synthase. Our results suggest that Trolox-derived antioxidants are promising candidates in therapy development for human mitochondrial disorders.

Establishing Pragmatic Discriminations among the Communicative Functions of Requesting, Rejecting, and Commenting in an Adolescent.

ERIC Educational Resources Information Center

Reichle, Joe; And Others

1984-01-01

A 15-year-old with severe handicaps who exhibited minimal intentional communicative behavior was taught to discriminately encode three classes of communicative functions. Results suggest that pragmatic discriminations can be established early in a sequence of communication intervention. The S used requesting and rejecting spontaneously in other…

Genomic profiling of host responses to Lassa virus: therapeutic potential from primate to man

PubMed Central

Zapata, Juan C; Salvato, Maria S

2015-01-01

Lassa virus infection elicits distinctive changes in host gene expression and metabolism. We focus on changes in host gene expression that may be biomarkers that discriminate individual pathogens or may help to provide a prognosis for disease. In addition to assessing mRNA changes, functional studies are also needed to discriminate causes of disease from mechanisms of host resistance. Host responses that drive pathogenesis are likely to be targets for prevention or therapy. Host responses to Lassa or its related arenaviruses have been monitored in cell culture, in animal models of hemorrhagic fever, in Lassa-infected nonhuman primates and, to a limited extent, in infected human beings. Here, we describe results from those studies and discuss potential targets for reducing virus replication and mitigating disease. PMID:25844088

A Theory of Self- Nonself Discrimination

ERIC Educational Resources Information Center

Bretscher, Peter; Cohn, Melvin

1970-01-01

Theoretical model suggests antigen-sensitive cells produce antibodies only when two antigenic determinants are recognized, and explains self-nonself discrimination by antibody system. Specific antigen-sensitive cells accumulate in absence of foreign antigens and co-operate to induce antibodies if antigen enter the body; but antigen-sensitive cells…

Novel Acoustic Scattering Processes for Target Discrimination

DTIC Science & Technology

2014-12-31

Woods Hole Oceanographic Institution. WORK COMPLETED During FY10, in addition to La Follett’s thesis [6] a publication appeared based primarily on...function of tilt angle is very similar to the case in which the cylinder is hung adjacent to a flat floating platform of closed-cell extruded ...departed during FY10 who are currently employed at NSWC-PCD and remain involved in related research. Dr. Baik [5] is currently a postdoc at Woods Hole

Expression of NK cell receptors on decidual T cells in human pregnancy.

PubMed

Tilburgs, Tamara; van der Mast, Barbara J; Nagtzaam, Nicole M A; Roelen, Dave L; Scherjon, Sicco A; Claas, Frans H J

2009-06-01

Specific receptors enable NK cells to discriminate between cells with normal expression of MHC class I and cells that have low or absent expression of MHC class I molecules. In addition to NK cells, these receptors can be expressed on T cell subsets, mainly on CD8+ T cells but also on gammadeltaTCR+ T cells and CD4+ T cells. Although the function of NK cell receptor expression on T cells is not completely understood, various studies have shown that they are involved in down regulation of T cell receptor (TCR)-mediated activation and influence effector functions, like cytotoxicity and cytokine production. The aim of this study was to analyze expression of NK cell receptors on peripheral blood and decidual T cells during human pregnancy using flow cytometry. We demonstrate that a proportion of decidual T cells express HLA-C specific killer immunoglobulin-like receptors (KIRs). Furthermore, a small proportion of decidual T cells express the HLA-E specific CD94-NKG2A inhibitory and CD94-NKG2C activating receptors. Decidual KIR+ and CD94-NKG2+ T cells mainly display a CD3+CD4-CD8- phenotype. However, decidual tissue also contains higher percentages of KIR and CD94-NKG2 expressing CD4+ and CD8+ T cells compared to peripheral blood. So far, the functional capacities of decidual T cells expressing the NK cell receptors are unknown but NK cell receptor expression on decidual T cells may provide an alternative means by which decidual T cells distinguish self (maternal) cells from allogeneic fetal cells, and act to modulate the decidual immune response.

A dual-channel fluorescent chemosensor for discriminative detection of glutathione based on functionalized carbon quantum dots.

PubMed

Huang, Yuanyuan; Zhou, Jin; Feng, Hui; Zheng, Jieyu; Ma, Hui-Min; Liu, Weidong; Tang, Cong; Ao, Hang; Zhao, Meizhi; Qian, Zhaosheng

2016-12-15

A convenient, fluorescent dual-channel chemosensor on the basis of bis(3-pyridylmethyl)amine-functionalized carbon quantum dots (BPMA-CQDs) nanoprobe was constructed, and it can discriminatively detect glutathione from its analogues cysteine and homocysteine based on two distinctive strategies. Two distinct fluorescence responses of BPMA-CQDs probe to Cu(II) and Ag(I) were identified and further employed to achieve selective detection of Cu(II) and Ag(I) respectively. Based on the BPMA-CQDs/Cu(II) conjugate, discriminative detection of GSH was achieved in terms of correlation between the amounts of GSH and fluorescence recovery. The addition of GSH into BPMA-CQDs/Cu(II) system induces the reduction of Cu(II) to Cu(I), which could efficiently block PET process resulting in the following fluorescence recovery. Based on the BPMA-CQDs/Ag(I) conjugate, GSH assay could also be established on the basis of fluorescence response to GSH. The introduction of GSH into the preceding system triggers the competitive coordination to Ag(I) between BPMA and GSH, and silver ions are finally taken away by GSH from the probe, where the fluorescence is restored to its original weak state. Both of the detection strategies can achieve discriminative detection of GSH from Cys and Hcy. The assays showed good stability and repeatability, and covered a broad linear range of up to 13.3μM with a lowest detection limit of 42.0nM. Moreover, both of them were utilized to monitor GSH level in live cells. Copyright © 2016 Elsevier B.V. All rights reserved.

The Use of Raman Tweezers and Chemometric Analysis to Discriminate the Urological Cell Lines, PC-3, LNCaP, BPH and MGH-U1

NASA Astrophysics Data System (ADS)

Harvey, T. J.; Hughes, C.; Ward, A. D.; Gazi, E.; Faria, E. Correia; Clarke, N. W.; Brown, M.; Snook, R.; Gardner, P.

2008-11-01

Here we report on investigations into using Raman optical tweezers to analyse both live and chemically fixed prostate and bladder cells. Spectra were subjected to chemometric analysis to discriminate and classify the cell types based on their spectra. Subsequent results revealed the potential of Raman tweezers as a potential clinical diagnostic tool.

Two distinct HLA-A0201-presented epitopes of the Wilms tumor antigen 1 can function as targets for leukemia-reactive CTL.

PubMed

Bellantuono, Ilaria; Gao, Liquan; Parry, Suzanne; Marley, Steve; Dazzi, Francesco; Apperley, Jane; Goldman, John M; Stauss, Hans J

2002-11-15

Using the allo-restricted T-cell approach to circumvent tolerance, we have previously identified a cytotoxic T-lymphocyte (CTL) epitope in the transcription factor Wilms tumor antigen 1 (WT1) presented by HLA-A0201 (A2) class I molecules. Here we describe an additional A2-presented epitope and show that CTLs against both epitopes kill WT1-expressing leukemia cell lines. Colony-forming assays demonstrated that both types of CTL killed CD34(+) progenitor cells from A2(+) leukemia patients, but not from A2(+) healthy individuals. The long-term culture-initiating cell (LTC-IC) assay was used to analyze the killing activity of WT1-specific CTLs against the more immature fraction of CD34(+) cells. The CTLs killed LTC-ICs of patients with chronic myelogenous leukemia (CML), whereas the function of normal CD34(+) progenitor/stem cells was not inhibited. Together, the data show that CTLs specific for 2 distinct peptide epitopes of WT1 can discriminate between normal and leukemia LTC-ICs, suggesting that such CTLs have the potential to selectively kill CML progenitor/stem cells.

Sex estimation standards for medieval and contemporary Croats

PubMed Central

Bašić, Željana; Kružić, Ivana; Jerković, Ivan; Anđelinović, Deny; Anđelinović, Šimun

2017-01-01

Aim To develop discriminant functions for sex estimation on medieval Croatian population and test their application on contemporary Croatian population. Methods From a total of 519 skeletons, we chose 84 adult excellently preserved skeletons free of antemortem and postmortem changes and took all standard measurements. Sex was estimated/determined using standard anthropological procedures and ancient DNA (amelogenin analysis) where pelvis was insufficiently preserved or where sex morphological indicators were not consistent. We explored which measurements showed sexual dimorphism and used them for developing univariate and multivariate discriminant functions for sex estimation. We included only those functions that reached accuracy rate ≥80%. We tested the applicability of developed functions on modern Croatian sample (n = 37). Results From 69 standard skeletal measurements used in this study, 56 of them showed statistically significant sexual dimorphism (74.7%). We developed five univariate discriminant functions with classification rate 80.6%-85.2% and seven multivariate discriminant functions with an accuracy rate of 81.8%-93.0%. When tested on the modern population functions showed classification rates 74.1%-100%, and ten of them reached aimed accuracy rate. Females showed higher classification rates in the medieval populations, whereas males were better classified in the modern populations. Conclusion Developed discriminant functions are sufficiently accurate for reliable sex estimation in both medieval Croatian population and modern Croatian samples and may be used in forensic settings. The methodological issues that emerged regarding the importance of considering external factors in development and application of discriminant functions for sex estimation should be further explored. PMID:28613039

Altered intestinal microbiota and blood T cell phenotype are shared by patients with Crohn's disease and their unaffected siblings.

PubMed

Hedin, Charlotte R; McCarthy, Neil E; Louis, Petra; Farquharson, Freda M; McCartney, Sara; Taylor, Kirstin; Prescott, Natalie J; Murrells, Trevor; Stagg, Andrew J; Whelan, Kevin; Lindsay, James O

2014-10-01

Crohn's disease (CD) is associated with intestinal dysbiosis, altered blood T cell populations, elevated faecal calprotectin (FC) and increased intestinal permeability (IP). CD-associated features present in siblings (increased risk of CD) but not in healthy controls, provide insight into early CD pathogenesis. We aimed to (1) Delineate the genetic, immune and microbiological profile of patients with CD, their siblings and controls and (2) Determine which factors discriminate between groups. Faecal microbiology was analysed by quantitative PCR targeting 16S ribosomal RNA, FC by ELISA, blood T cell phenotype by flow cytometry and IP by differential lactulose-rhamnose absorption in 22 patients with inactive CD, 21 of their healthy siblings and 25 controls. Subject's genotype relative risk was determined by Illumina Immuno BeadChip. Strikingly, siblings shared aspects of intestinal dysbiosis with patients with CD (lower concentrations of Faecalibacterium prausnitzii (p=0.048), Clostridia cluster IV (p=0.003) and Roseburia spp. (p=0.09) compared with controls). As in CD, siblings demonstrated a predominance of memory T cells (p=0.002) and elevated naïve CD4 T cell β7 integrin expression (p=0.01) compared with controls. FC was elevated (>50 μg/g) in 8/21 (38%) siblings compared with 2/25 (8%) controls (p=0.028); whereas IP did not differ between siblings and controls. Discriminant function analysis determined that combinations of these factors significantly discriminated between groups (χ(2)=80.4, df=20, p<0.001). Siblings were separated from controls by immunological and microbiological variables. Healthy siblings of patients with CD manifest immune and microbiological abnormalities associated with CD distinct from their genotype-related risk and provide an excellent model in which to investigate early CD pathogenesis. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Hilar Mossy Cell Degeneration Causes Transient Dentate Granule Cell Hyperexcitability and Impaired Pattern Separation

PubMed Central

Jinde, Seiichiro; Zsiros, Veronika; Jiang, Zhihong; Nakao, Kazuhito; Pickel, James; Kohno, Kenji; Belforte, Juan E.; Nakazawa, Kazu

2012-01-01

Summary Although excitatory mossy cells of the hippocampal hilar region are known to project both to dentate granule cells and to interneurons, it is as yet unclear whether mossy cell activity’s net effect on granule cells is excitatory or inhibitory. To explore their influence on dentate excitability and hippocampal function, we generated a conditional transgenic mouse line, using the Cre/loxP system, in which diphtheria toxin receptor was selectively expressed in mossy cells. One week after injecting toxin into this line, mossy cells throughout the longitudinal axis were degenerated extensively, theta wave power of dentate local field potentials increased during exploration, and deficits occurred in contextual discrimination. By contrast, we detected no epileptiform activity, spontaneous behavioral seizures, or mossy-fiber sprouting 5–6 weeks after mossy cell degeneration. These results indicate that the net effect of mossy cell excitation is to inhibit granule cell activity and enable dentate pattern separation. PMID:23259953

Perceived Discrimination and Longitudinal Change in Kidney Function Among Urban Adults.

PubMed

Beydoun, May A; Poggi-Burke, Angedith; Zonderman, Alan B; Rostant, Ola S; Evans, Michele K; Crews, Deidra C

2017-09-01

Perceived discrimination has been associated with psychosocial distress and adverse health outcomes. We examined associations of perceived discrimination measures with changes in kidney function in a prospective cohort study, the Healthy Aging in Neighborhoods of Diversity across the Life Span. Our study included 1620 participants with preserved baseline kidney function (estimated glomerular filtration rate [eGFR] ≥ 60 mL/min/1.73 m) (662 whites and 958 African Americans, aged 30-64 years). Self-reported perceived racial discrimination and perceived gender discrimination (PGD) and a general measure of experience of discrimination (EOD) ("medium versus low," "high versus low") were examined in relation to baseline, follow-up, and annual rate of change in eGFR using multiple mixed-effects regression (γbase, γrate) and ordinary least square models (γfollow). Perceived gender discrimination "high versus low PGD" was associated with a lower baseline eGFR in all models (γbase = -3.51 (1.34), p = .009 for total sample). Among white women, high EOD was associated with lower baseline eGFR, an effect that was strengthened in the full model (γbase = -5.86 [2.52], p = .020). Overall, "high versus low" PGD was associated with lower follow-up eGFR (γfollow = -3.03 [1.45], p = .036). Among African American women, both perceived racial discrimination and PGD were linked to lower follow-up kidney function, an effect that was attenuated with covariate adjustment, indicating mediation through health-related, psychosocial, and lifestyle factors. In contrast, EOD was not linked to follow-up eGFR in any of the sex by race groups. Perceived racial and gender discrimination are associated with lower kidney function assessed by glomerular filtration rate and the strength of associations differ by sex and race groups. Perceived discrimination deserves further investigation as a psychosocial risk factors for kidney disease.

Functional sensibility of the hand in leprosy patients.

PubMed

van Brakel, W H; Kets, C M; van Leerdam, M E; Khawas, I B; Gurung, K S

1997-03-01

The aims of this cross-sectional comparative study was to compare the results of Semmes-Weinstein monofilament testing (SWM) and moving 2-point discrimination (M2PD) with four tests of functional sensibility: recognition of objects, discrimination of size and texture and detection of dots. Ninety-eight leprosy in- and outpatients at Green Pastures Hospital in Pokhara, Nepal were tested with each of the above tests and the results were compared to see how well they agreed. Using the tests of functional sensibility as reference points, we examined the validity of the SWM and M2PD as predictors of functional sensibility. There was definite, but only moderate correlation between thresholds of monofilaments and M2PD and functional sensibility of the hand. A normal result with the SWM and/or M2PD had a good predictive value for normal functional sensibility. Sensitivity was reasonable against recognition of objects and discrimination of textures as reference tests (80-90% and 88-93%), but poor against discrimination of size and detection of dots (50-75% and 43-65%). Specificity was high for most combinations of SWM or M2PD with any of the tests of functional sensibility (85-99%). Above a monofilament threshold of 2 g, the predictive value of an abnormal test was 100% for dot detection and 83-92% for textural discrimination. This indicates that impairment of touch sensibility at this level correlates well with loss of dot detection and textural discrimination in patients with leprous neuropathy. For M2PD the pattern was very similar. Above a threshold of 5 mm, 95-100% of affected hands had loss of dot detection and 73-80% had loss of textural discrimination. Monofilament testing and M2PD did not seem suitable as proxy measures of functional sensibility of the hand in leprosy patients. However, a normal threshold with monofilaments and/or M2PD had a good predictive value for normal functional sensibility. Above a monofilament threshold of 2 g and/or a M2PD threshold of 5 mm, textural discrimination was abnormal in most hands.

How discriminating are discriminative instruments?

PubMed

Hankins, Matthew

2008-05-27

The McMaster framework introduced by Kirshner & Guyatt is the dominant paradigm for the development of measures of health status and health-related quality of life (HRQL). The framework defines the functions of such instruments as evaluative, predictive or discriminative. Evaluative instruments are required to be sensitive to change (responsiveness), but there is no corresponding index of the degree to which discriminative instruments are sensitive to cross-sectional differences. This paper argues that indices of validity and reliability are not sufficient to demonstrate that a discriminative instrument performs its function of discriminating between individuals, and that the McMaster framework would be augmented by the addition of a separate index of discrimination. The coefficient proposed by Ferguson (Delta) is easily adapted to HRQL instruments and is a direct, non-parametric index of the degree to which an instrument distinguishes between individuals. While Delta should prove useful in the development and evaluation of discriminative instruments, further research is required to elucidate the relationship between the measurement properties of discrimination, reliability and responsiveness.

Determination of sex from the hyoid bone in a contemporary White population.

PubMed

Logar, Ciara J; Peckmann, Tanya R; Meek, Susan; Walls, Stephen G

2016-04-01

Six discriminant functions, developed from an historic White population, were tested on a contemporary White population for determination of sex from the hyoid. One hundred and thirty four fused and unfused hyoids from a contemporary White population were used. Individuals ranged between 20 and 49 years old. Six historic White discriminant functions were applied to the fused and unfused hyoids of the pooled contemporary White population, i.e. all males and females and all age ranges combined. The overall accuracy rates were between 72.1% and 92.3%. Correct sex determination for contemporary White males ranged between 88.2% and 96.3%, while correct sex determination for contemporary White females ranged between 31.3% and 92.0%. Discriminant functions were created for the contemporary White population with overall mean accuracy rates between 67.0% and 93.0%. The multivariate discriminant function overall accuracy rates were between 89.0% and 93.0% and the univariate discriminant function overall accuracy rates were between 67.0% and 86.8%. The contemporary White population data were compared to other populations and showed significant differences between many of the variables measured. This study illustrated the need for population-specific and temporally-specific discriminant functions for determination of sex from the hyoid bone. Copyright © 2016 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.

Understanding disease mechanisms with models of signaling pathway activities.

PubMed

Sebastian-Leon, Patricia; Vidal, Enrique; Minguez, Pablo; Conesa, Ana; Tarazona, Sonia; Amadoz, Alicia; Armero, Carmen; Salavert, Francisco; Vidal-Puig, Antonio; Montaner, David; Dopazo, Joaquín

2014-10-25

Understanding the aspects of the cell functionality that account for disease or drug action mechanisms is one of the main challenges in the analysis of genomic data and is on the basis of the future implementation of precision medicine. Here we propose a simple probabilistic model in which signaling pathways are separated into elementary sub-pathways or signal transmission circuits (which ultimately trigger cell functions) and then transforms gene expression measurements into probabilities of activation of such signal transmission circuits. Using this model, differential activation of such circuits between biological conditions can be estimated. Thus, circuit activation statuses can be interpreted as biomarkers that discriminate among the compared conditions. This type of mechanism-based biomarkers accounts for cell functional activities and can easily be associated to disease or drug action mechanisms. The accuracy of the proposed model is demonstrated with simulations and real datasets. The proposed model provides detailed information that enables the interpretation disease mechanisms as a consequence of the complex combinations of altered gene expression values. Moreover, it offers a framework for suggesting possible ways of therapeutic intervention in a pathologically perturbed system.

Tailoring a psychophysical discrimination experiment upon assessment of the psychometric function: Predictions and results

NASA Astrophysics Data System (ADS)

Vilardi, Andrea; Tabarelli, Davide; Ricci, Leonardo

2015-02-01

Decision making is a widespread research topic and plays a crucial role in neuroscience as well as in other research and application fields of, for example, biology, medicine and economics. The most basic implementation of decision making, namely binary discrimination, is successfully interpreted by means of signal detection theory (SDT), a statistical model that is deeply linked to physics. An additional, widespread tool to investigate discrimination ability is the psychometric function, which measures the probability of a given response as a function of the magnitude of a physical quantity underlying the stimulus. However, the link between psychometric functions and binary discrimination experiments is often neglected or misinterpreted. Aim of the present paper is to provide a detailed description of an experimental investigation on a prototypical discrimination task and to discuss the results in terms of SDT. To this purpose, we provide an outline of the theory and describe the implementation of two behavioural experiments in the visual modality: upon the assessment of the so-called psychometric function, we show how to tailor a binary discrimination experiment on performance and decisional bias, and to measure these quantities on a statistical base. Attention is devoted to the evaluation of uncertainties, an aspect which is also often overlooked in the scientific literature.

Multiple Levels of Suffering: Discrimination in Health-Care Settings is Associated With Enhanced Laboratory Pain Sensitivity in Sickle Cell Disease.

PubMed

Mathur, Vani A; Kiley, Kasey B; Haywood, Carlton; Bediako, Shawn M; Lanzkron, Sophie; Carroll, C Patrick; Buenaver, Luis F; Pejsa, Megan; Edwards, Robert R; Haythornthwaite, Jennifer A; Campbell, Claudia M

2016-12-01

People living with sickle cell disease (SCD) experience severe episodic and chronic pain and frequently report poor interpersonal treatment within health-care settings. In this particularly relevant context, we examined the relationship between perceived discrimination and both clinical and laboratory pain. Seventy-one individuals with SCD provided self-reports of experiences with discrimination in health-care settings and clinical pain severity, and completed a psychophysical pain testing battery in the laboratory. Discrimination in health-care settings was correlated with greater clinical pain severity and enhanced sensitivity to multiple laboratory-induced pain measures, as well as stress, depression, and sleep. After controlling for relevant covariates, discrimination remained a significant predictor of mechanical temporal summation (a marker of central pain facilitation), but not clinical pain severity or suprathreshold heat pain response. Furthermore, a significant interaction between experience with discrimination and clinical pain severity was associated with mechanical temporal summation; increased experience with discrimination was associated with an increased correlation between clinical pain severity and temporal summation of pain. Perceived discrimination within health-care settings was associated with pain facilitation. These findings suggest that discrimination may be related to increased central sensitization among SCD patients, and more broadly that health-care social environments may interact with pain pathophysiology.

Soft X-ray astronomy proportional counter electronics

NASA Technical Reports Server (NTRS)

Gardner, W. R.

1971-01-01

The X-ray multiwire proportional counter is designed to measure cosmic X-ray fluxes at sounding rocket altitudes in the energy range of 0.1 to 10 keV. Four instruments will be launched in a Black Brant 4 rocket employing different combinations of detector windows and gas. The detector is constructed with two layers of twelve cells. A columnator is mounted on the face of one layer whose cells are wired together alternately to form two main detector sections. The electronics and gas regulation systems are mounted on the face of the second layer whose cells are wired together to form one anticoincidence detector section. Normally X-rays will have short ionization paths in only one of the main detector cells at a time and won't enter the anticoincidence detector cells. To distinguish between X-rays and charged particles, the instrument includes a coincidence discriminator, an anticoincidence discriminator, and a pulse rise time discriminator.

Prediction of cognitive outcome based on the progression of auditory discrimination during coma.

PubMed

Juan, Elsa; De Lucia, Marzia; Tzovara, Athina; Beaud, Valérie; Oddo, Mauro; Clarke, Stephanie; Rossetti, Andrea O

2016-09-01

To date, no clinical test is able to predict cognitive and functional outcome of cardiac arrest survivors. Improvement of auditory discrimination in acute coma indicates survival with high specificity. Whether the degree of this improvement is indicative of recovery remains unknown. Here we investigated if progression of auditory discrimination can predict cognitive and functional outcome. We prospectively recorded electroencephalography responses to auditory stimuli of post-anoxic comatose patients on the first and second day after admission. For each recording, auditory discrimination was quantified and its evolution over the two recordings was used to classify survivors as "predicted" when it increased vs. "other" if not. Cognitive functions were tested on awakening and functional outcome was assessed at 3 months using the Cerebral Performance Categories (CPC) scale. Thirty-two patients were included, 14 "predicted survivors" and 18 "other survivors". "Predicted survivors" were more likely to recover basic cognitive functions shortly after awakening (ability to follow a standardized neuropsychological battery: 86% vs. 44%; p=0.03 (Fisher)) and to show a very good functional outcome at 3 months (CPC 1: 86% vs. 33%; p=0.004 (Fisher)). Moreover, progression of auditory discrimination during coma was strongly correlated with cognitive performance on awakening (phonemic verbal fluency: rs=0.48; p=0.009 (Spearman)). Progression of auditory discrimination during coma provides early indication of future recovery of cognitive functions. The degree of improvement is informative of the degree of functional impairment. If confirmed in a larger cohort, this test would be the first to predict detailed outcome at the single-patient level. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Protein social behavior makes a stronger signal for partner identification than surface geometry.

PubMed

Laine, Elodie; Carbone, Alessandra

2017-01-01

Cells are interactive living systems where proteins movements, interactions and regulation are substantially free from centralized management. How protein physico-chemical and geometrical properties determine who interact with whom remains far from fully understood. We show that characterizing how a protein behaves with many potential interactors in a complete cross-docking study leads to a sharp identification of its cellular/true/native partner(s). We define a sociability index, or S-index, reflecting whether a protein likes or not to pair with other proteins. Formally, we propose a suitable normalization function that accounts for protein sociability and we combine it with a simple interface-based (ranking) score to discriminate partners from non-interactors. We show that sociability is an important factor and that the normalization permits to reach a much higher discriminative power than shape complementarity docking scores. The social effect is also observed with more sophisticated docking algorithms. Docking conformations are evaluated using experimental binding sites. These latter approximate in the best possible way binding sites predictions, which have reached high accuracy in recent years. This makes our analysis helpful for a global understanding of partner identification and for suggesting discriminating strategies. These results contradict previous findings claiming the partner identification problem being solvable solely with geometrical docking. Proteins 2016; 85:137-154. © 2016 Wiley Periodicals, Inc. © 2016 The Authors Proteins: Structure, Function, and Bioinformatics Published by Wiley Periodicals, Inc.

Detection and discrimination of colour, a comparison of physiological and psychophysical data

NASA Astrophysics Data System (ADS)

Valberg, A.; Lee, B. B.

1989-01-01

Whereas the physiological basis of colorimetry (colour matches) is well understood in terms of the trireceptor theory of colour vision, colour discrimination and scaling still lack a comparable foundation. We present here experimental data that demonstrate how sensitivity and responsiveness of different types of cone-opponent and non-opponent cells of the macaque monkey correlate with human threshold sensitivity on the one hand, and how they in combination can be used to construct a suprathreshold equidistant colour space. Psychophysical thresholds correlate well with the threshold envelope of the most sensitive cells when stimuli are projected upon a steady white background. Detection thresholds for stimuli of differing wavelength and purity (saturation) generally indicate a transition from a phasic non-opponent system to a tonic opponent system of on-centre cells as purity increases. Detection and chromatic discrimination thresholds coincide only for long and short wavelengths of high purity, whereas they differ for mid-spectral lights. Different cell types may thus support detection and discrimination with different stimuli. With chromatic scaling of surface colours on the other hand, when stimuli are darker than an adaptation field still other cell types are needed. We demonstrate that it is possible, from a combination of on- and off-opponent cells, to reconstruct a uniform colour space, using summed outputs of cells with the same cone combination and vector addition for cells with different combinations. Different hues are represented by opponent cells with inputs from different cone types, the hue percept being related to the ratio of the activities of these cell systems.

The glycosphingolipid P₁ is an ovarian cancer-associated carbohydrate antigen involved in migration.

PubMed

Jacob, F; Anugraham, M; Pochechueva, T; Tse, B W C; Alam, S; Guertler, R; Bovin, N V; Fedier, A; Hacker, N F; Huflejt, M E; Packer, N; Heinzelmann-Schwarz, V A

2014-10-14

The level of plasma-derived naturally circulating anti-glycan antibodies (AGA) to P1 trisaccharide has previously been shown to significantly discriminate between ovarian cancer patients and healthy women. Here we aim to identify the Ig class that causes this discrimination, to identify on cancer cells the corresponding P1 antigen recognised by circulating anti-P1 antibodies and to shed light into the possible function of this glycosphingolipid. An independent Australian cohort was assessed for the presence of anti-P1 IgG and IgM class antibodies using suspension array. Monoclonal and human derived anti-glycan antibodies were verified using three independent glycan-based immunoassays and flow cytometry-based inhibition assay. The P1 antigen was detected by LC-MS/MS and flow cytometry. FACS-sorted cell lines were studied on the cellular migration by colorimetric assay and real-time measurement using xCELLigence system. Here we show in a second independent cohort (n=155) that the discrimination of cancer patients is mediated by the IgM class of anti-P1 antibodies (P=0.0002). The presence of corresponding antigen P1 and structurally related epitopes in fresh tissue specimens and cultured cancer cells is demonstrated. We further link the antibody and antigen (P1) by showing that human naturally circulating and affinity-purified anti-P1 IgM isolated from patients ascites can bind to naturally expressed P1 on the cell surface of ovarian cancer cells. Cell-sorted IGROV1 was used to obtain two study subpopulations (P1-high, 66.1%; and P1-low, 33.3%) and observed that cells expressing high P1-levels migrate significantly faster than those with low P1-levels. This is the first report showing that P1 antigen, known to be expressed on erythrocytes only, is also present on ovarian cancer cells. This suggests that P1 is a novel tumour-associated carbohydrate antigen recognised by the immune system in patients and may have a role in cell migration. The clinical value of our data may be both diagnostic and prognostic; patients with low anti-P1 IgM antibodies present with a more aggressive phenotype and earlier relapse.

Novel single-cell functional analysis of red blood cells using laser tweezers Raman spectroscopy: application for sickle cell disease.

PubMed

Liu, Rui; Mao, Ziliang; Matthews, Dennis L; Li, Chin-Shang; Chan, James W; Satake, Noriko

2013-07-01

Laser tweezers Raman spectroscopy was used to characterize the oxygenation response of single normal adult, sickle, and cord blood red blood cells (RBCs) to an applied mechanical force. Individual cells were subjected to different forces by varying the laser power of a single-beam optical trap, and the intensities of several oxygenation-specific Raman spectral peaks were monitored to determine the oxygenation state of the cells. For all three cell types, an increase in laser power (or mechanical force) induced a greater deoxygenation of the cell. However, sickle RBCs deoxygenated more readily than normal RBCs when subjected to the same optical forces. Conversely, cord blood RBCs were able to maintain their oxygenation better than normal RBCs. These results suggest that differences in the chemical or mechanical properties of fetal, normal, and sickle cells affect the degree to which applied mechanical forces can deoxygenate the cell. Populations of normal, sickle, and cord RBCs were identified and discriminated based on this mechanochemical phenomenon. This study demonstrates the potential application of laser tweezers Raman spectroscopy as a single-cell, label-free analytical tool to characterize the functional (e.g., mechanical deformability, oxygen binding) properties of normal and diseased RBCs. Copyright © 2013 ISEH - Society for Hematology and Stem Cells. Published by Elsevier Inc. All rights reserved.

Assessment Tools for Identifying Functional Limitations Associated With Functional Ankle Instability

PubMed Central

Ross, Scott E; Guskiewicz, Kevin M; Gross, Michael T; Yu, Bing

2008-01-01

Context: Assessment tools should identify functional limitations associated with functional ankle instability (FAI) by discriminating unstable from stable ankles. Objective: To identify assessment tools that discriminated FAI from stable ankles and determine the most accurate assessment tool for discriminating between FAI and stable ankles. Design: Case-control study. Setting: Research laboratory. Patients or Other Participants: Fifteen individuals with FAI and 15 healthy individuals; participants with unilateral FAI reported “giving-way” sensations and ankle sprains, whereas healthy participants did not. Intervention(s): Participants answered 12 questions on the Ankle Joint Functional Assessment Tool (AJFAT). They also performed a single-leg jump landing, which required them to jump to half their maximum jump height, land on a single leg, and stabilize quickly on a force plate. Main Outcome Measure(s): Receiver operating characteristic curves determined cutoff scores for discriminating between ankle groups for AJFAT total score and resultant vector (RV) time to stabilization. Accuracy values for discriminating between groups were determined by calculating the area under the receiver operating characteristic curves. Results: The cutoff score for discriminating between FAI and stable ankles was ≥26 (sensitivity  =  1, specificity  =  1) and ≥1.58 seconds (sensitivity  =  0.67, specificity  =  0.73) for the AJFAT total score and RV time to stabilization, respectively. The area under the curve for the AJFAT was 1.0 (asymptotic significance <.05), whereas the RV time to stabilization had an area under the curve of 0.72 (asymptotic significance <.05). Conclusions: The AJFAT was an excellent assessment tool for discriminating between ankle groups, whereas RV time to stabilization was a fair assessment tool. Although both assessments discriminated between ankle groups, the AJFAT more accurately discriminated between groups than the RV time to stabilization did. Future researchers should confirm these findings using a prospective research design. PMID:18335012

Stimulus function in simultaneous discrimination1

PubMed Central

Biederman, Gerald B.

1968-01-01

In discrimination learning, the negativity of the stimulus correlated with nonreinforcement (S−) declines after 100 training trials while the stimulus correlated with reinforcement (S+) is paradoxically more positive with lesser amounts of discrimination training. Training subjects on two simultaneous discrimination tasks revealed a within-subjects overlearning reversal effect, where a more-frequently presented discrimination problem was better learned in reversal than was a discrimination problem presented less frequently during training. PMID:5672254

Chemoselective detection and discrimination of carbonyl-containing compounds in metabolite mixtures by 1H-detected 15N NMR

PubMed Central

Lane, Andrew N.; Arumugam, Sengodagounder; Lorkiewicz, Pawel K.; Higashi, Richard M.; Laulhé, Sébastien; Nantz, Michael H.; Moseley, Hunter N.B.; Fan, Teresa W.-M.

2015-01-01

NMR spectra of mixtures of metabolites extracted from cells or tissues are extremely complex, reflecting the large number of compounds that are present over a wide range of concentrations. Although multidimensional NMR can greatly improve resolution as well as improve reliability of compound assignments, lower abundance metabolites often remain hidden. We have developed a carbonyl selective aminooxy probe that specifically reacts with free keto and aldehyde functions, but not carboxylates. By incorporating 15N in the aminooxy functional group, 15N-edited NMR was used to select exclusively those metabolites that contain a free carbonyl function while all other metabolites are rejected. Here we demonstrate that the chemical shifts of the aminooxy adducts of ketones and aldehydes are very different, which can be used to discriminate between aldoses and ketoses for example. Utilizing the 2 or 3 bond 15N-1H couplings, the 15N-edited NMR analysis was optimized first with authentic standards and then applied to an extract of the lung adenocarcinoma cell line A549. More than 30 carbonyl containing compounds at NMR detectable levels, 6 of which we have assigned by reference to our database. As the aminooxy probe contains a permanently charged quaternary ammonium group, the adducts are also optimized for detection by mass spectrometry. Thus, this sample preparation technique provides a better link between the two structural determination tools, thereby paving the way to faster and more reliable identification of both known and unknown metabolites directly in crude biological extracts. PMID:25616249

Cortical actin nanodynamics determines nitric oxide release in vascular endothelium.

PubMed

Fels, Johannes; Jeggle, Pia; Kusche-Vihrog, Kristina; Oberleithner, Hans

2012-01-01

The release of the main vasodilator nitric oxide (NO) by the endothelial NO synthase (eNOS) is a hallmark of endothelial function. We aim at elucidating the underlying mechanism how eNOS activity depends on cortical stiffness (К(cortex)) of living endothelial cells. It is hypothesized that cortical actin dynamics determines К(cortex) and directly influences eNOS activity. By combined atomic force microscopy and fluorescence imaging we generated mechanical and optical sections of single living cells. This approach allows the discrimination between К(cortex) and bulk cell stiffness (К(bulk)) and, additionally, the simultaneous analysis of submembranous actin web dynamics. We show that К(cortex) softens when cortical F-actin depolymerizes and that this shift from a gel-like stiff cortex to a soft G-actin rich layer, triggers the stiffness-sensitive eNOS activity. The results implicate that stiffness changes in the ∼100 nm phase of the submembranous actin web, without affecting К(bulk), regulate NO release and thus determines endothelial function.

Clathrin-independent pathways do not contribute significantly to endocytic flux

PubMed Central

Bitsikas, Vassilis; Corrêa, Ivan R; Nichols, Benjamin J

2014-01-01

Several different endocytic pathways have been proposed to function in mammalian cells. Clathrin-coated pits are well defined, but the identity, mechanism and function of alternative pathways have been controversial. Here we apply universal chemical labelling of plasma membrane proteins to define all primary endocytic vesicles, and labelling of specific proteins with a reducible SNAP-tag substrate. These approaches provide high temporal resolution and stringent discrimination between surface-connected and intracellular membranes. We find that at least 95% of the earliest detectable endocytic vesicles arise from clathrin-coated pits. GPI-anchored proteins, candidate cargoes for alternate pathways, are also found to enter the cell predominantly via coated pits. Experiments employing a mutated clathrin adaptor reveal distinct mechanisms for sorting into coated pits, and thereby explain differential effects on the uptake of transferrin and GPI-anchored proteins. These data call for a revision of models for the activity and diversity of endocytic pathways in mammalian cells. DOI: http://dx.doi.org/10.7554/eLife.03970.001 PMID:25232658

Differentiating sex and species of Western Grebes (Aechmophorus occidentalis) and Clark's Grebes (Aechmophorus clarkii) and their eggs using external morphometrics and discriminant function analysis

USGS Publications Warehouse

Hartman, C. Alex; Ackerman, Joshua T.; Eagles-Smith, Collin A.; Herzog, Mark

2016-01-01

In birds where males and females are similar in size and plumage, sex determination by alternative means is necessary. Discriminant function analysis based on external morphometrics was used to distinguish males from females in two closely related species: Western Grebe (Aechmophorus occidentalis) and Clark's Grebe (A. clarkii). Additionally, discriminant function analysis was used to evaluate morphometric divergence between Western and Clark's grebe adults and eggs. Aechmophorus grebe adults (n = 576) and eggs (n = 130) were sampled across 29 lakes and reservoirs throughout California, USA, and adult sex was determined using molecular analysis. Both Western and Clark's grebes exhibited considerable sexual size dimorphism. Males averaged 6–26% larger than females among seven morphological measurements, with the greatest sexual size dimorphism occurring for bill morphometrics. Discriminant functions based on bill length, bill depth, and short tarsus length correctly assigned sex to 98% of Western Grebes, and a function based on bill length and bill depth correctly assigned sex to 99% of Clark's Grebes. Further, a simplified discriminant function based only on bill depth correctly assigned sex to 96% of Western Grebes and 98% of Clark's Grebes. In contrast, external morphometrics were not suitable for differentiating between Western and Clark's grebe adults or their eggs, with correct classification rates of discriminant functions of only 60%, 63%, and 61% for adult males, adult females, and eggs, respectively. Our results indicate little divergence in external morphology between species of Aechmophorus grebes, and instead separation is much greater between males and females.

Nanosurface design of dental implants for improved cell growth and function

NASA Astrophysics Data System (ADS)

Pan, Hsu-An; Hung, Yao-Ching; Chiou, Jin-Chern; Tai, Shih-Ming; Chen, Hsin-Hung; Huang, G. Steven

2012-08-01

A strategy was proposed for the topological design of dental implants based on an in vitro survey of optimized nanodot structures. An in vitro survey was performed using nanodot arrays with dot diameters ranging from 10 to 200 nm. MG63 osteoblasts were seeded on nanodot arrays and cultured for 3 days. Cell number, percentage undergoing apoptotic-like cell death, cell adhesion and cytoskeletal organization were evaluated. Nanodots with a diameter of approximately 50 nm enhanced cell number by 44%, minimized apoptotic-like cell death to 2.7%, promoted a 30% increase in microfilament bundles and maximized cell adhesion with a 73% increase in focal adhesions. An enhancement of about 50% in mineralization was observed, determined by von Kossa staining and by Alizarin Red S staining. Therefore, we provide a complete range of nanosurfaces for growing osteoblasts to discriminate their nanoscale environment. Nanodot arrays present an opportunity to positively and negatively modulate cell behavior and maturation. Our results suggest a topological approach which is beneficial for the design of dental implants.

Pavlovian Extinction of the Discriminative Stimulus Effects of Nicotine and Ethanol in Rats Varies as a Function of Context

ERIC Educational Resources Information Center

Troisi, Joseph R., II

2011-01-01

Operant extinction contingencies can undermine the discriminative stimulus effects of drugs. Here, nicotine (0.4 mg/kg) and ethanol (0.8 g/kg) first functioned as either an S[superscript D] or S[superscript Delta], in a counterbalanced one-lever go/no-go (across sessions) operant drug discrimination procedure. Pavlovian extinction in the training…

Distinct lateral inhibitory circuits drive parallel processing of sensory information in the mammalian olfactory bulb

PubMed Central

Geramita, Matthew A; Burton, Shawn D; Urban, Nathan N

2016-01-01

Splitting sensory information into parallel pathways is a common strategy in sensory systems. Yet, how circuits in these parallel pathways are composed to maintain or even enhance the encoding of specific stimulus features is poorly understood. Here, we have investigated the parallel pathways formed by mitral and tufted cells of the olfactory system in mice and characterized the emergence of feature selectivity in these cell types via distinct lateral inhibitory circuits. We find differences in activity-dependent lateral inhibition between mitral and tufted cells that likely reflect newly described differences in the activation of deep and superficial granule cells. Simulations show that these circuit-level differences allow mitral and tufted cells to best discriminate odors in separate concentration ranges, indicating that segregating information about different ranges of stimulus intensity may be an important function of these parallel sensory pathways. DOI: http://dx.doi.org/10.7554/eLife.16039.001 PMID:27351103

Heparan Sulfates Support Pyramidal Cell Excitability, Synaptic Plasticity, and Context Discrimination.

PubMed

Minge, Daniel; Senkov, Oleg; Kaushik, Rahul; Herde, Michel K; Tikhobrazova, Olga; Wulff, Andreas B; Mironov, Andrey; van Kuppevelt, Toin H; Oosterhof, Arie; Kochlamazashvili, Gaga; Dityatev, Alexander; Henneberger, Christian

2017-02-01

Heparan sulfate (HS) proteoglycans represent a major component of the extracellular matrix and are critical for brain development. However, their function in the mature brain remains to be characterized. Here, acute enzymatic digestion of HS side chains was used to uncover how HSs support hippocampal function in vitro and in vivo. We found that long-term potentiation (LTP) of synaptic transmission at CA3-CA1 Schaffer collateral synapses was impaired after removal of highly sulfated HSs with heparinase 1. This reduction was associated with decreased Ca2+ influx during LTP induction, which was the consequence of a reduced excitability of CA1 pyramidal neurons. At the subcellular level, heparinase treatment resulted in reorganization of the distal axon initial segment, as detected by a reduction in ankyrin G expression. In vivo, digestion of HSs impaired context discrimination in a fear conditioning paradigm and oscillatory network activity in the low theta band after fear conditioning. Thus, HSs maintain neuronal excitability and, as a consequence, support synaptic plasticity and learning. © The Author 2017. Published by Oxford University Press.

An electroglottographical analysis-based discriminant function model differentiating multiple sclerosis patients from healthy controls.

PubMed

Vavougios, George D; Doskas, Triantafyllos; Konstantopoulos, Kostas

2018-05-01

Dysarthrophonia is a predominant symptom in many neurological diseases, affecting the quality of life of the patients. In this study, we produced a discriminant function equation that can differentiate MS patients from healthy controls, using electroglottographic variables not analyzed in a previous study. We applied stepwise linear discriminant function analysis in order to produce a function and score derived from electroglottographic variables extracted from a previous study. The derived discriminant function's statistical significance was determined via Wilk's λ test (and the associated p value). Finally, a 2 × 2 confusion matrix was used to determine the function's predictive accuracy, whereas the cross-validated predictive accuracy is estimated via the "leave-one-out" classification process. Discriminant function analysis (DFA) was used to create a linear function of continuous predictors. DFA produced the following model (Wilk's λ = 0.043, χ2 = 388.588, p < 0.0001, Tables 3 and 4): D (MS vs controls) = 0.728*DQx1 mean monologue + 0.325*CQx monologue + 0.298*DFx1 90% range monologue + 0.443*DQx1 90% range reading - 1.490*DQx1 90% range monologue. The derived discriminant score (S1) was used subsequently in order to form the coordinates of a ROC curve. Thus, a cutoff score of - 0.788 for S1 corresponded to a perfect classification (100% sensitivity and 100% specificity, p = 1.67e -22 ). Consistent with previous findings, electroglottographic evaluation represents an easy to implement and potentially important assessment in MS patients, achieving adequate classification accuracy. Further evaluation is needed to determine its use as a biomarker.

Two sides of the same coin? Unraveling subtle differences between human embryonic and induced pluripotent stem cells by Raman spectroscopy.

PubMed

Parrotta, Elvira; De Angelis, Maria Teresa; Scalise, Stefania; Candeloro, Patrizio; Santamaria, Gianluca; Paonessa, Mariagrazia; Coluccio, Maria Laura; Perozziello, Gerardo; De Vitis, Stefania; Sgura, Antonella; Coluzzi, Elisa; Mollace, Vincenzo; Di Fabrizio, Enzo Mario; Cuda, Giovanni

2017-11-28

Human pluripotent stem cells, including embryonic stem cells and induced pluripotent stem cells, hold enormous promise for many biomedical applications, such as regenerative medicine, drug testing, and disease modeling. Although induced pluripotent stem cells resemble embryonic stem cells both morphologically and functionally, the extent to which these cell lines are truly equivalent, from a molecular point of view, remains controversial. Principal component analysis and K-means cluster analysis of collected Raman spectroscopy data were used for a comparative study of the biochemical fingerprint of human induced pluripotent stem cells and human embryonic stem cells. The Raman spectra analysis results were further validated by conventional biological assays. Raman spectra analysis revealed that the major difference between human embryonic stem cells and induced pluripotent stem cells is due to the nucleic acid content, as shown by the strong positive peaks at 785, 1098, 1334, 1371, 1484, and 1575 cm -1 , which is enriched in human induced pluripotent stem cells. Here, we report a nonbiological approach to discriminate human induced pluripotent stem cells from their native embryonic stem cell counterparts.

GFP-complementation assay to detect functional CPP and protein delivery into living cells

PubMed Central

Milech, Nadia; Longville, Brooke AC; Cunningham, Paula T; Scobie, Marie N; Bogdawa, Heique M; Winslow, Scott; Anastasas, Mark; Connor, Theresa; Ong, Ferrer; Stone, Shane R; Kerfoot, Maria; Heinrich, Tatjana; Kroeger, Karen M; Tan, Yew-Foon; Hoffmann, Katrin; Thomas, Wayne R; Watt, Paul M; Hopkins, Richard M

2015-01-01

Efficient cargo uptake is essential for cell-penetrating peptide (CPP) therapeutics, which deliver widely diverse cargoes by exploiting natural cell processes to penetrate the cell’s membranes. Yet most current CPP activity assays are hampered by limitations in assessing uptake, including confounding effects of conjugated fluorophores or ligands, indirect read-outs requiring secondary processing, and difficulty in discriminating internalization from endosomally trapped cargo. Split-complementation Endosomal Escape (SEE) provides the first direct assay visualizing true cytoplasmic-delivery of proteins at biologically relevant concentrations. The SEE assay has minimal background, is amenable to high-throughput processes, and adaptable to different transient and stable cell lines. This split-GFP-based platform can be useful to study transduction mechanisms, cellular imaging, and characterizing novel CPPs as pharmaceutical delivery agents in the treatment of disease. PMID:26671759

Optimal observation network design for conceptual model discrimination and uncertainty reduction

NASA Astrophysics Data System (ADS)

Pham, Hai V.; Tsai, Frank T.-C.

2016-02-01

This study expands the Box-Hill discrimination function to design an optimal observation network to discriminate conceptual models and, in turn, identify a most favored model. The Box-Hill discrimination function measures the expected decrease in Shannon entropy (for model identification) before and after the optimal design for one additional observation. This study modifies the discrimination function to account for multiple future observations that are assumed spatiotemporally independent and Gaussian-distributed. Bayesian model averaging (BMA) is used to incorporate existing observation data and quantify future observation uncertainty arising from conceptual and parametric uncertainties in the discrimination function. In addition, the BMA method is adopted to predict future observation data in a statistical sense. The design goal is to find optimal locations and least data via maximizing the Box-Hill discrimination function value subject to a posterior model probability threshold. The optimal observation network design is illustrated using a groundwater study in Baton Rouge, Louisiana, to collect additional groundwater heads from USGS wells. The sources of uncertainty creating multiple groundwater models are geological architecture, boundary condition, and fault permeability architecture. Impacts of considering homoscedastic and heteroscedastic future observation data and the sources of uncertainties on potential observation areas are analyzed. Results show that heteroscedasticity should be considered in the design procedure to account for various sources of future observation uncertainty. After the optimal design is obtained and the corresponding data are collected for model updating, total variances of head predictions can be significantly reduced by identifying a model with a superior posterior model probability.

The interaction between hippocampal GABA-B and cannabinoid receptors upon spatial change and object novelty discrimination memory function.

PubMed

Nasehi, Mohammad; Alaghmandan-Motlagh, Niyousha; Ebrahimi-Ghiri, Mohaddeseh; Nami, Mohammad; Zarrindast, Mohammad-Reza

2017-10-01

Previous studies have postulated functional links between GABA and cannabinoid systems in the hippocampus. The aim of the present study was to investigate any possible interaction between these systems in spatial change and object novelty discrimination memory consolidation in the dorsal hippocampus (CA1 region) of NMRI mice. Assessment of the spatial change and object novelty discrimination memory function was carried out in a non-associative task. The experiment comprised mice exposure to an open field containing five objects followed by the examination of their reactivity to object displacement (spatial change) and object substitution (object novelty) after three sessions of habituation. Our results showed that the post-training intraperitoneal administration of the higher dose of ACPA (0.02 mg/kg) impaired both spatial change and novelty discrimination memory functions. Meanwhile, the higher dose of GABA-B receptor agonist, baclofen, impaired the spatial change memory by itself. Moreover, the post-training intra-CA1 microinjection of a subthreshold dose of baclofen increased the ACPA effect on spatial change and novelty discrimination memory at a lower and higher dose, respectively. On the other hand, the lower and higher but not mid-level doses of GABA-B receptor antagonist, phaclofen, could reverse memory deficits induced by ACPA. However, phaclofen at its mid-level dose impaired the novelty discrimination memory and whereas the higher dose impaired the spatial change memory. Based on our findings, GABA-B receptors in the CA1 region appear to modulate the ACPA-induced cannabinoid CB1 signaling upon spatial change and novelty discrimination memory functions.

Discriminant functions for sex estimation of modern Japanese skulls.

PubMed

Ogawa, Yoshinori; Imaizumi, Kazuhiko; Miyasaka, Sachio; Yoshino, Mineo

2013-05-01

The purpose of this study is to generate a set of discriminant functions in order to estimate the sex of modern Japanese skulls. To conduct the analysis, the anthropological measurement data of 113 individuals (73 males and 40 females) were collected from recent forensic anthropological test records at the National Research Institute of Police Science, Japan. Birth years of the individuals ranged from 1926 to 1979, and age at death was over 19 years for all individuals. A total of 10 anthropological measurements were used in the discriminant function analysis: maximum cranial length, cranial base length, maximum cranial breadth, maximum frontal breadth, basion-bregmatic height, upper facial breadth, bizygomatic breadth, bicondylar breadth, bigonial breadth, and ramal height. As a result, nine discriminant functions were established. The classification accuracy ranged from 79.0 to 89.9% when the measurements of the 113 individuals were substituted into the established functions, from 77.8 to 88.1% when a leave-one-out cross-validation procedure was applied to the data, and from 86.7 to 93.0% when the measurements of 50 new individuals (25 males and 25 females), unrelated to the establishment of the discriminant functions, were used. Copyright © 2012 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.

Two Methods for Teaching Simple Visual Discriminations to Learners with Severe Disabilities

ERIC Educational Resources Information Center

Graff, Richard B.; Green, Gina

2004-01-01

Simple discriminations are involved in many functional skills; additionally, they are components of conditional discriminations (identity and arbitrary matching-to-sample), which are involved in a wide array of other important performances. Many individuals with severe disabilities have difficulty acquiring simple discriminations with standard…

Activation of Premotor Vocal Areas during Musical Discrimination

ERIC Educational Resources Information Center

Brown, Steven; Martinez, Michael J.

2007-01-01

Two same/different discrimination tasks were performed by amateur-musician subjects in this functional magnetic resonance imaging study: Melody Discrimination and Harmony Discrimination. Both tasks led to activations not only in classic working memory areas--such as the cingulate gyrus and dorsolateral prefrontal cortex--but in a series of…

Deficits in recognition, identification, and discrimination of facial emotions in patients with bipolar disorder.

PubMed

Benito, Adolfo; Lahera, Guillermo; Herrera, Sara; Muncharaz, Ramón; Benito, Guillermo; Fernández-Liria, Alberto; Montes, José Manuel

2013-01-01

To analyze the recognition, identification, and discrimination of facial emotions in a sample of outpatients with bipolar disorder (BD). Forty-four outpatients with diagnosis of BD and 48 matched control subjects were selected. Both groups were assessed with tests for recognition (Emotion Recognition-40 - ER40), identification (Facial Emotion Identification Test - FEIT), and discrimination (Facial Emotion Discrimination Test - FEDT) of facial emotions, as well as a theory of mind (ToM) verbal test (Hinting Task). Differences between groups were analyzed, controlling the influence of mild depressive and manic symptoms. Patients with BD scored significantly lower than controls on recognition (ER40), identification (FEIT), and discrimination (FEDT) of emotions. Regarding the verbal measure of ToM, a lower score was also observed in patients compared to controls. Patients with mild syndromal depressive symptoms obtained outcomes similar to patients in euthymia. A significant correlation between FEDT scores and global functioning (measured by the Functioning Assessment Short Test, FAST) was found. These results suggest that, even in euthymia, patients with BD experience deficits in recognition, identification, and discrimination of facial emotions, with potential functional implications.

Assessment of Differential Item Functioning in the Experiences of Discrimination Index

PubMed Central

Cunningham, Timothy J.; Berkman, Lisa F.; Gortmaker, Steven L.; Kiefe, Catarina I.; Jacobs, David R.; Seeman, Teresa E.; Kawachi, Ichiro

2011-01-01

The psychometric properties of instruments used to measure self-reported experiences of discrimination in epidemiologic studies are rarely assessed, especially regarding construct validity. The authors used 2000–2001 data from the Coronary Artery Risk Development in Young Adults (CARDIA) Study to examine differential item functioning (DIF) in 2 versions of the Experiences of Discrimination (EOD) Index, an index measuring self-reported experiences of racial/ethnic and gender discrimination. DIF may confound interpretation of subgroup differences. Large DIF was observed for 2 of 7 racial/ethnic discrimination items: White participants reported more racial/ethnic discrimination for the “at school” item, and black participants reported more racial/ethnic discrimination for the “getting housing” item. The large DIF by race/ethnicity in the index for racial/ethnic discrimination probably reflects item impact and is the result of valid group differences between blacks and whites regarding their respective experiences of discrimination. The authors also observed large DIF by race/ethnicity for 3 of 7 gender discrimination items. This is more likely to have been due to item bias. Users of the EOD Index must consider the advantages and disadvantages of DIF adjustment (omitting items, constructing separate measures, and retaining items). The EOD Index has substantial usefulness as an instrument that can assess self-reported experiences of discrimination. PMID:22038104

The prediction of human exons by oligonucleotide composition and discriminant analysis of spliceable open reading frames

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

Solovyev, V.V.; Salamov, A.A.; Lawrence, C.B.

1994-12-31

Discriminant analysis is applied to the problem of recognition 5`-, internal and 3`-exons in human DNA sequences. Specific recognition functions were developed for revealing exons of particular types. The method based on a splice site prediction algorithm that uses the linear Fisher discriminant to combine the information about significant triplet frequencies of various functional parts of splice site regions and preferences of oligonucleotide in protein coding and nation regions. The accuracy of our splice site recognition function is about 97%. A discriminant function for 5`-exon prediction includes hexanucleotide composition of upstream region, triplet composition around the ATG codon, ORF codingmore » potential, donor splice site potential and composition of downstream introit region. For internal exon prediction, we combine in a discriminant function the characteristics describing the 5`- intron region, donor splice site, coding region, acceptor splice site and Y-intron region for each open reading frame flanked by GT and AG base pairs. The accuracy of precise internal exon recognition on a test set of 451 exon and 246693 pseudoexon sequences is 77% with a specificity of 79% and a level of pseudoexon ORF prediction of 99.96%. The recognition quality computed at the level of individual nucleotides is 89%, for exon sequences and 98% for intron sequences. A discriminant function for 3`-exon prediction includes octanucleolide composition of upstream nation region, triplet composition around the stop codon, ORF coding potential, acceptor splice site potential and hexanucleotide composition of downstream region. We unite these three discriminant functions in exon predicting program FEX (find exons). FEX exactly predicts 70% of 1016 exons from the test of 181 complete genes with specificity 73%, and 89% exons are exactly or partially predicted. On the average, 85% of nucleotides were predicted accurately with specificity 91%.« less

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

Ashenfelter, J.; Jaffe, D.; Diwan, M. V.

A meter-long, 23-liter EJ-309 liquid scintillator detector has been constructed to study the light collection and pulse-shape discrimination performance of elongated scintillator cells for the PROSPECT reactor antineutrino experiment. The magnitude and uniformity of light collection and neutron-gamma discrimination power in the energy range of antineutrino inverse beta decay products have been studied using gamma and spontaneous fission calibration sources deployed along the cell axis. We also study neutron-gamma discrimination and light collection abilities for differing PMT and reflector configurations. As a result, key design features for optimizing MeV-scale response and background rejection capabilities are identified.

Does the high nucleic acid content of individual bacterial cells allow us to discriminate between active cells and inactive cells in aquatic systems?

PubMed

Lebaron, P; Servais, P; Agogué, H; Courties, C; Joux, F

2001-04-01

The nucleic acid contents of individual bacterial cells as determined with three different nucleic acid-specific fluorescent dyes (SYBR I, SYBR II, and SYTO 13) and flow cytometry were compared for different seawater samples. Similar fluorescence patterns were observed, and bacteria with high apparent nucleic acid contents (HNA) could be discriminated from bacteria with low nucleic acid contents (LNA). The best discrimination between HNA and LNA cells was found when cells were stained with SYBR II. Bacteria in different water samples collected from seven freshwater, brackish water, and seawater ecosystems were prelabeled with tritiated leucine and then stained with SYBR II. After labeling and staining, HNA, LNA, and total cells were sorted by flow cytometry, and the specific activity of each cellular category was determined from leucine incorporation rates. The HNA cells were responsible for most of the total bacterial production, and the specific activities of cells in the HNA population varied between samples by a factor of seven. We suggest that nucleic acid content alone can be a better indicator of the fraction of growing cells than total counts and that this approach should be combined with other fluorescent physiological probes to improve detection of the most active cells in aquatic systems.

Does the High Nucleic Acid Content of Individual Bacterial Cells Allow Us To Discriminate between Active Cells and Inactive Cells in Aquatic Systems?

PubMed Central

Lebaron, Philippe; Servais, Pierre; Agogué, Helene; Courties, Claude; Joux, Fabien

2001-01-01

The nucleic acid contents of individual bacterial cells as determined with three different nucleic acid-specific fluorescent dyes (SYBR I, SYBR II, and SYTO 13) and flow cytometry were compared for different seawater samples. Similar fluorescence patterns were observed, and bacteria with high apparent nucleic acid contents (HNA) could be discriminated from bacteria with low nucleic acid contents (LNA). The best discrimination between HNA and LNA cells was found when cells were stained with SYBR II. Bacteria in different water samples collected from seven freshwater, brackish water, and seawater ecosystems were prelabeled with tritiated leucine and then stained with SYBR II. After labeling and staining, HNA, LNA, and total cells were sorted by flow cytometry, and the specific activity of each cellular category was determined from leucine incorporation rates. The HNA cells were responsible for most of the total bacterial production, and the specific activities of cells in the HNA population varied between samples by a factor of seven. We suggest that nucleic acid content alone can be a better indicator of the fraction of growing cells than total counts and that this approach should be combined with other fluorescent physiological probes to improve detection of the most active cells in aquatic systems. PMID:11282632

Characterization of Microbiota in Children with Chronic Functional Constipation.

PubMed

de Meij, Tim G J; de Groot, Evelien F J; Eck, Anat; Budding, Andries E; Kneepkens, C M Frank; Benninga, Marc A; van Bodegraven, Adriaan A; Savelkoul, Paul H M

2016-01-01

Disruption of the intestinal microbiota is considered an etiological factor in pediatric functional constipation. Scientifically based selection of potential beneficial probiotic strains in functional constipation therapy is not feasible due to insufficient knowledge of microbiota composition in affected subjects. The aim of this study was to describe microbial composition and diversity in children with functional constipation, compared to healthy controls. Fecal samples from 76 children diagnosed with functional constipation according to the Rome III criteria (median age 8.0 years; range 4.2-17.8) were analyzed by IS-pro, a PCR-based microbiota profiling method. Outcome was compared with intestinal microbiota profiles of 61 healthy children (median 8.6 years; range 4.1-17.9). Microbiota dissimilarity was depicted by principal coordinate analysis (PCoA), diversity was calculated by Shannon diversity index. To determine the most discriminative species, cross validated logistic ridge regression was performed. Applying total microbiota profiles (all phyla together) or per phylum analysis, no disease-specific separation was observed by PCoA and by calculation of diversity indices. By ridge regression, however, functional constipation and controls could be discriminated with 82% accuracy. Most discriminative species were Bacteroides fragilis, Bacteroides ovatus, Bifidobacterium longum, Parabacteroides species (increased in functional constipation) and Alistipes finegoldii (decreased in functional constipation). None of the commonly used unsupervised statistical methods allowed for microbiota-based discrimination of children with functional constipation and controls. By ridge regression, however, both groups could be discriminated with 82% accuracy. Optimization of microbiota-based interventions in constipated children warrants further characterization of microbial signatures linked to clinical subgroups of functional constipation.

Caspase Activity Is Required for Engulfment of Apoptotic Cells

PubMed Central

Shklyar, Boris; Levy-Adam, Flonia; Mishnaevski, Ketty

2013-01-01

Clearance of apoptotic cells by phagocytic neighbors is crucial for normal development of multicellular organisms. However, how phagocytes discriminate between healthy and dying cells remains poorly understood. We focus on glial phagocytosis of apoptotic neurons during development of the Drosophila central nervous system. We identified phosphatidylserine (PS) as a ligand on apoptotic cells for the phagocytic receptor Six Microns Under (SIMU) and report that PS alone is not sufficient for engulfment. Our data reveal that, additionally to PS exposure, caspase activity is required for clearance of apoptotic cells by phagocytes. Here we demonstrate that SIMU recognizes and binds PS on apoptotic cells through its N-terminal EMILIN (EMI), Nimrod 1 (NIM1), and NIM2 repeats, whereas the C-terminal NIM3 and NIM4 repeats control SIMU affinity to PS. Based on the structure-function analysis of SIMU, we discovered a novel mechanism of internal inhibition responsible for differential affinities of SIMU to its ligand which might prevent elimination of living cells exposing PS on their surfaces. PMID:23754750

Infectious polymorphic toxins delivered by outer membrane exchange discriminate kin in myxobacteria.

PubMed

Vassallo, Christopher N; Cao, Pengbo; Conklin, Austin; Finkelstein, Hayley; Hayes, Christopher S; Wall, Daniel

2017-08-18

Myxobacteria are known for complex social behaviors including outer membrane exchange (OME), in which cells exchange large amounts of outer membrane lipids and proteins upon contact. The TraA cell surface receptor selects OME partners based on a variable domain. However, traA polymorphism alone is not sufficient to precisely discriminate kin. Here, we report a novel family of OME-delivered toxins that promote kin discrimination of OME partners. These SitA lipoprotein toxins are polymorphic and widespread in myxobacteria. Each sitA is associated with a cognate sitI immunity gene, and in some cases a sitB accessory gene. Remarkably, we show that SitA is transferred serially between target cells, allowing the toxins to move cell-to-cell like an infectious agent. Consequently, SitA toxins define strong identity barriers between strains and likely contribute to population structure, maintenance of cooperation, and strain diversification. Moreover, these results highlight the diversity of systems evolved to deliver toxins between bacteria.

Sexing California Clapper Rails using morphological measurements

USGS Publications Warehouse

Overton, Cory T.; Casazza, Michael L.; Takekawa, John Y.; Rohmer, Tobias M.

2009-01-01

California Clapper Rails (Rallus longirostris obsoletus) have monomorphic plumage, a trait that makes identification of sex difficult without extensive behavioral observation or genetic testing. Using 31 Clapper Rails (22 females, 9 males), caught in south San Francisco Bay, CA, and using easily measurable morphological characteristics, we developed a discriminant function to distinguish sex. We then validated this function on 33 additional rails. Seven morphological measurements were considered, resulting in three which were selected in the discriminate function: culmen length, tarsometatarsus length, and flat wing length. We had no classification errors for the development or testing datasets either with resubstitution or cross-validation procedures. Male California Clapper Rails were 6-22% larger than females for individual morphological traits, and the largest difference was in body mass.  Variables in our discriminant function closely match variables developed for sexing Clapper Rails of Gulf Coast populations. However, a universal discriminant function to sex all Clapper Rail subspecies is not likely because of large and inconsistent differences in morphological traits among subspecies. 

Expression of GARP selectively identifies activated human FOXP3+ regulatory T cells.

PubMed

Wang, Rui; Kozhaya, Lina; Mercer, Frances; Khaitan, Alka; Fujii, Hodaka; Unutmaz, Derya

2009-08-11

The molecules that define human regulatory T cells (Tregs) phenotypically and functionally remain to be fully characterized. We recently showed that activated human Tregs express mRNA for a transmembrane protein called glycoprotein A repetitions predominant (GARP, or LRRC32). Here, using a GARP-specific mAb, we demonstrate that expression of GARP on activated Tregs correlates with their suppressive capacity. However, GARP was not induced on T cells activated in the presence of TGFbeta, which expressed high levels of FOXP3 and lacked suppressive function. Ectopic expression of FOXP3 in conventional T cells was also insufficient for induction of GARP expression in most donors. Functionally, silencing GARP in Tregs only moderately attenuated their suppressive activity. CD25+ T cells sorted for high GARP expression displayed more potent suppressive activity compared with CD25+GARP- cells. Remarkably, CD25+GARP- T cells expanded in culture contained 3-5 fold higher IL-17-secreting cells compared with either CD25+GARP+ or CD25-GARP- cells, suggesting that high GARP expression can potentially discriminate Tregs from those that have switched to Th17 lineage. We also determined whether GARP expression correlates with FOXP3-expressing T cells in human immunodeficiency virus (HIV) -infected subjects. A subset of HIV+ individuals with high percentages of FOXP3+ T cells did not show proportionate increase in GARP+ T cells. This finding suggests that higher FOXP3 levels observed in these HIV+ individuals is possibly due to immune activation rather than to an increase in Tregs. Our findings highlight the significance of GARP both in dissecting duality of Treg/Th17 cell differentiation and as a marker to identify bona fide Tregs during diseases with chronic immune activation.

Expression of GARP selectively identifies activated human FOXP3+ regulatory T cells

PubMed Central

Wang, Rui; Kozhaya, Lina; Mercer, Frances; Khaitan, Alka; Fujii, Hodaka; Unutmaz, Derya

2009-01-01

The molecules that define human regulatory T cells (Tregs) phenotypically and functionally remain to be fully characterized. We recently showed that activated human Tregs express mRNA for a transmembrane protein called glycoprotein A repetitions predominant (GARP, or LRRC32). Here, using a GARP-specific mAb, we demonstrate that expression of GARP on activated Tregs correlates with their suppressive capacity. However, GARP was not induced on T cells activated in the presence of TGFβ, which expressed high levels of FOXP3 and lacked suppressive function. Ectopic expression of FOXP3 in conventional T cells was also insufficient for induction of GARP expression in most donors. Functionally, silencing GARP in Tregs only moderately attenuated their suppressive activity. CD25+ T cells sorted for high GARP expression displayed more potent suppressive activity compared with CD25+GARP− cells. Remarkably, CD25+GARP− T cells expanded in culture contained 3–5 fold higher IL-17-secreting cells compared with either CD25+GARP+ or CD25−GARP− cells, suggesting that high GARP expression can potentially discriminate Tregs from those that have switched to Th17 lineage. We also determined whether GARP expression correlates with FOXP3-expressing T cells in human immunodeficiency virus (HIV) −infected subjects. A subset of HIV+ individuals with high percentages of FOXP3+ T cells did not show proportionate increase in GARP+ T cells. This finding suggests that higher FOXP3 levels observed in these HIV+ individuals is possibly due to immune activation rather than to an increase in Tregs. Our findings highlight the significance of GARP both in dissecting duality of Treg/Th17 cell differentiation and as a marker to identify bona fide Tregs during diseases with chronic immune activation. PMID:19666573

Variation of facial features among three African populations: Body height match analyses.

PubMed

Taura, M G; Adamu, L H; Gudaji, A

2017-01-01

Body height is one of the variables that show a correlation with facial craniometry. Here we seek to discriminate the three populations (Nigerians, Ugandans and Kenyans) using facial craniometry based on different categories of body height of adult males. A total of 513 individuals comprising 234 Nigerians, 169 Ugandans and 110 Kenyans with mean age of 25.27, s=5.13 (18-40 years) participated. Paired and unpaired facial features were measured using direct craniometry. Multivariate and stepwise discriminate function analyses were used for differentiation of the three populations. The result showed significant overall facial differences among the three populations in all the body height categories. Skull height, total facial height, outer canthal distance, exophthalmometry, right ear width and nasal length were significantly different among the three different populations irrespective of body height categories. Other variables were sensitive to body height. Stepwise discriminant function analyses included maximum of six variables for better discrimination between the three populations. The single best discriminator of the groups was total facial height, however, for body height >1.70m the single best discriminator was nasal length. Most of the variables were better used with function 1, hence, better discrimination than function 2. In conclusion, adult body height in addition to other factors such as age, sex, and ethnicity should be considered in making decision on facial craniometry. However, not all the facial linear dimensions were sensitive to body height. Copyright © 2016 Elsevier GmbH. All rights reserved.

A Preliminary Discriminant and Convergent Validity Study of the Teacher Functional Behavioral Assessment Checklist.

ERIC Educational Resources Information Center

Stage, Scott A.; Cheney, Douglas; Walker, Bridget; LaRocque, Michelle

2002-01-01

Examines discriminant and convergent validity of the Teacher Functional Behavior Assessment Checklist (TFBAC) using 89 first- through third-grade students. Results are discussed in terms of increasing the convergent validity of the TFBAC, teacher training in concepts about functional behavioral assessment and the possibility of concurrent…

Item Information and Discrimination Functions for Trinary PCM Items.

ERIC Educational Resources Information Center

Akkermans, Wies; Muraki, Eiji

1997-01-01

For trinary partial credit items, the shape of the item information and item discrimination functions is examined in relation to the item parameters. Conditions under which these functions are unimodal and bimodal are discussed, and the locations and values of maxima are derived. Practical relevance of the results is discussed. (SLD)

Lateral interactions in the outer retina

PubMed Central

Thoreson, Wallace B.; Mangel, Stuart C.

2012-01-01

Lateral interactions in the outer retina, particularly negative feedback from horizontal cells to cones and direct feed-forward input from horizontal cells to bipolar cells, play a number of important roles in early visual processing, such as generating center-surround receptive fields that enhance spatial discrimination. These circuits may also contribute to post-receptoral light adaptation and the generation of color opponency. In this review, we examine the contributions of horizontal cell feedback and feed-forward pathways to early visual processing. We begin by reviewing the properties of bipolar cell receptive fields, especially with respect to modulation of the bipolar receptive field surround by the ambient light level and to the contribution of horizontal cells to the surround. We then review evidence for and against three proposed mechanisms for negative feedback from horizontal cells to cones: 1) GABA release by horizontal cells, 2) ephaptic modulation of the cone pedicle membrane potential generated by currents flowing through hemigap junctions in horizontal cell dendrites, and 3) modulation of cone calcium currents (ICa) by changes in synaptic cleft proton levels. We also consider evidence for the presence of direct horizontal cell feed-forward input to bipolar cells and discuss a possible role for GABA at this synapse. We summarize proposed functions of horizontal cell feedback and feed-forward pathways. Finally, we examine the mechanisms and functions of two other forms of lateral interaction in the outer retina: negative feedback from horizontal cells to rods and positive feedback from horizontal cells to cones. PMID:22580106

Functionalization of nanotextured substrates for enhanced identification of metastatic breast cancer cells

NASA Astrophysics Data System (ADS)

Mansur, Nuzhat; Raziul Hasan, Mohammad; Kim, Young-tae; Iqbal, Samir M.

2017-09-01

Metastasis is the major cause of low survival rates among cancer patients. Once cancer cells metastasize, it is extremely difficult to contain the disease. We report on a nanotextured platform for enhanced detection of metastatic cells. We captured metastatic (MDA-MDB-231) and non-metastatic (MCF-7) breast cancer cells on anti-EGFR aptamer modified plane and nanotextured substrates. Metastatic cells were seen to change their morphology at higher rates when captured on nanotextured substrates than on plane substrates. Analysis showed statistically different morphological behaviors of metastatic cells that were very pronounced on the nanotextured substrates. Several distance matrices were calculated to quantify the dissimilarity of cell shape change. Nanotexturing increased the dissimilarity of the metastatic cells and as a result the contrast between metastatic and non-metastatic cells increased. Jaccard distance measurements found that the shape change ratio of the non-metastatic and metastatic cells was enhanced from 1:1.01 to 1:1.81, going from plane to nanotextured substrates. The shape change ratio of the non-metastatic to metastatic cells improved from 1:1.48 to 1:2.19 for the Hausdorff distance and from 1:1.87 to 1:4.69 for the Mahalanobis distance after introducing nanotexture. Distance matrix analysis showed that nanotexture increased the shape change ratios of non-metastatic and metastatic cells. Hence, the detectability of metastatic cells increased. These calculated matrices provided clear and explicit measures to discriminate single cells for their metastatic state on functional nanotextured substrates.

Simulation of synthetic discriminant function optical implementation

NASA Astrophysics Data System (ADS)

Riggins, J.; Butler, S.

1984-12-01

The optical implementation of geometrical shape and synthetic discriminant function matched filters is computer modeled. The filter implementation utilizes the Allebach-Keegan computer-generated hologram algorithm. Signal-to-noise and efficiency measurements were made on the resultant correlation planes.

Assessing Visuospatial Skills in Parkinson's: Comparison of Neuropsychological Assessment Battery Visual Discrimination to the Judgment of Line Orientation.

PubMed

Renfroe, Jenna B; Turner, Travis H; Hinson, Vanessa K

2017-02-01

Judgment of Line Orientation (JOLO) test is widely used in assessing visuospatial deficits in Parkinson's disease (PD). The neuropsychological assessment battery (NAB) offers the Visual Discrimination test, with age and education correction, parallel forms, and co-normed standardization sample for comparisons within and between domains. However, NAB Visual Discrimination has not been validated in PD, and may not measure the same construct as JOLO. A heterogeneous sample of 47 PD patients completed the JOLO and NAB Visual Discrimination within a broader neuropsychological evaluation. Pearson correlations assessed relationships between JOLO and NAB Visual Discrimination performances. Raw and demographically corrected scores from JOLO and Visual Discrimination were only weakly correlated. NAB Visual Discrimination subtest was moderately correlated with overall cognitive functioning, whereas the JOLO was not. Despite apparent virtues, results do not support NAB Visual Discrimination as an alternative to JOLO in assessing visuospatial functioning in PD. © The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Optimisation of wavelength modulated Raman spectroscopy: towards high throughput cell screening.

PubMed

Praveen, Bavishna B; Mazilu, Michael; Marchington, Robert F; Herrington, C Simon; Riches, Andrew; Dholakia, Kishan

2013-01-01

In the field of biomedicine, Raman spectroscopy is a powerful technique to discriminate between normal and cancerous cells. However the strong background signal from the sample and the instrumentation affects the efficiency of this discrimination technique. Wavelength Modulated Raman spectroscopy (WMRS) may suppress the background from the Raman spectra. In this study we demonstrate a systematic approach for optimizing the various parameters of WMRS to achieve a reduction in the acquisition time for potential applications such as higher throughput cell screening. The Signal to Noise Ratio (SNR) of the Raman bands depends on the modulation amplitude, time constant and total acquisition time. It was observed that the sampling rate does not influence the signal to noise ratio of the Raman bands if three or more wavelengths are sampled. With these optimised WMRS parameters, we increased the throughput in the binary classification of normal human urothelial cells and bladder cancer cells by reducing the total acquisition time to 6 s which is significantly lower in comparison to previous acquisition times required for the discrimination between similar cell types.

Phonological experience modulates voice discrimination: Evidence from functional brain networks analysis.

PubMed

Hu, Xueping; Wang, Xiangpeng; Gu, Yan; Luo, Pei; Yin, Shouhang; Wang, Lijun; Fu, Chao; Qiao, Lei; Du, Yi; Chen, Antao

2017-10-01

Numerous behavioral studies have found a modulation effect of phonological experience on voice discrimination. However, the neural substrates underpinning this phenomenon are poorly understood. Here we manipulated language familiarity to test the hypothesis that phonological experience affects voice discrimination via mediating the engagement of multiple perceptual and cognitive resources. The results showed that during voice discrimination, the activation of several prefrontal regions was modulated by language familiarity. More importantly, the same effect was observed concerning the functional connectivity from the fronto-parietal network to the voice-identity network (VIN), and from the default mode network to the VIN. Our findings indicate that phonological experience could bias the recruitment of cognitive control and information retrieval/comparison processes during voice discrimination. Therefore, the study unravels the neural substrates subserving the modulation effect of phonological experience on voice discrimination, and provides new insights into studying voice discrimination from the perspective of network interactions. Copyright © 2017. Published by Elsevier Inc.

Disruption of centrifugal inhibition to olfactory bulb granule cells impairs olfactory discrimination.

PubMed

Nunez-Parra, Alexia; Maurer, Robert K; Krahe, Krista; Smith, Richard S; Araneda, Ricardo C

2013-09-03

Granule cells (GCs) are the most abundant inhibitory neuronal type in the olfactory bulb and play a critical role in olfactory processing. GCs regulate the activity of principal neurons, the mitral cells, through dendrodendritic synapses, shaping the olfactory bulb output to other brain regions. GC excitability is regulated precisely by intrinsic and extrinsic inputs, and this regulation is fundamental for odor discrimination. Here, we used channelrhodopsin to stimulate GABAergic axons from the basal forebrain selectively and show that this stimulation generates reliable inhibitory responses in GCs. Furthermore, selective in vivo inhibition of GABAergic neurons in the basal forebrain by targeted expression of designer receptors exclusively activated by designer drugs produced a reversible impairment in the discrimination of structurally similar odors, indicating an important role of these inhibitory afferents in olfactory processing.

Community-based comprehensive intervention for people with schizophrenia in Guangzhou, China: Effects on clinical symptoms, social functioning, internalized stigma and discrimination.

PubMed

Li, Jie; Huang, Yuan-Guang; Ran, Mao-Sheng; Fan, Yu; Chen, Wen; Evans-Lacko, Sara; Thornicroft, Graham

2018-04-01

Comprehensive interventions including components of stigma and discrimination reduction in schizophrenia in low- and middle-income countries (LMICs) are lacking. We developed a community-based comprehensive intervention to evaluate its effects on clinical symptoms, social functioning, internalized stigma and discrimination among patients with schizophrenia. A randomized controlled trial including an intervention group (n = 169) and a control group (n = 158) was performed. The intervention group received comprehensive intervention (strategies against stigma and discrimination, psycho-education, social skills training and cognitive behavioral therapy) and the control group received face to face interview. Both lasted for nine months. Participants were measured at baseline, 6 months and 9 months using the Internalized Stigma of Mental Illness scale (ISMI), Discrimination and Stigma Scale (DISC-12), Global Assessment of Functioning (GAF), Schizophrenia Quality of Life Scale (SQLS), Self-Esteem Scale (SES), Brief Psychiatric Rating Scale (BPRS) and PANSS negative scale (PANSS-N). Insight and medication compliance were evaluated by senior psychiatrists. Data were analyzed by descriptive statistics, t-test, chi-square test or Fisher's exact test. Linear Mixed Models were used to show intervention effectiveness on scales. General Linear Mixed Models with multinomial logistic link function were used to assess the effectiveness on medication compliance and insight. We found a significant reduction on anticipated discrimination, BPRS and PANSS-N total scores, and an elevation on overcoming stigma and GAF in the intervention group after 9 months. These suggested the intervention may be effective in reducing anticipated discrimination, increasing skills overcoming stigma as well as improving clinical symptoms and social functioning in Chinese patients with schizophrenia. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

The lipid phenotype of breast cancer cells characterized by Raman microspectroscopy: towards a stratification of malignancy.

PubMed

Nieva, Claudia; Marro, Monica; Santana-Codina, Naiara; Rao, Satish; Petrov, Dmitri; Sierra, Angels

2012-01-01

Although molecular classification brings interesting insights into breast cancer taxonomy, its implementation in daily clinical care is questionable because of its expense and the information supplied in a single sample allocation is not sufficiently reliable. New approaches, based on a panel of small molecules derived from the global or targeted analysis of metabolic profiles of cells, have found a correlation between activation of de novo lipogenesis and poorer prognosis and shorter disease-free survival for many tumors. We hypothesized that the lipid content of breast cancer cells might be a useful indirect measure of a variety of functions coupled to breast cancer progression. Raman microspectroscopy was used to characterize metabolism of breast cancer cells with different degrees of malignancy. Raman spectra from MDA-MB-435, MDA-MB-468, MDA-MB-231, SKBR3, MCF7 and MCF10A cells were acquired with an InVia Raman microscope (Renishaw) with a backscattered configuration. We used Principal Component Analysis and Partial Least Squares Discriminant Analyses to assess the different profiling of the lipid composition of breast cancer cells. Characteristic bands related to lipid content were found at 3014, 2935, 2890 and 2845 cm(-1), and related to lipid and protein content at 2940 cm(-1). A classificatory model was generated which segregated metastatic cells and non-metastatic cells without basal-like phenotype with a sensitivity of 90% and a specificity of 82.1%. Moreover, expression of SREBP-1c and ABCA1 genes validated the assignation of the lipid phenotype of breast cancer cells. Indeed, changes in fatty acid unsaturation were related with the epithelial-to-mesenchymal transition phenotype. Raman microspectroscopy is a promising technique for characterizing and classifying the malignant phenotype of breast cancer cells on the basis of their lipid profiling. The algorithm for the discrimination of metastatic ability is a first step towards stratifying breast cancer cells using this rapid and reagent-free tool.

Enlightening discriminative network functional modules behind Principal Component Analysis separation in differential-omic science studies

PubMed Central

Ciucci, Sara; Ge, Yan; Durán, Claudio; Palladini, Alessandra; Jiménez-Jiménez, Víctor; Martínez-Sánchez, Luisa María; Wang, Yuting; Sales, Susanne; Shevchenko, Andrej; Poser, Steven W.; Herbig, Maik; Otto, Oliver; Androutsellis-Theotokis, Andreas; Guck, Jochen; Gerl, Mathias J.; Cannistraci, Carlo Vittorio

2017-01-01

Omic science is rapidly growing and one of the most employed techniques to explore differential patterns in omic datasets is principal component analysis (PCA). However, a method to enlighten the network of omic features that mostly contribute to the sample separation obtained by PCA is missing. An alternative is to build correlation networks between univariately-selected significant omic features, but this neglects the multivariate unsupervised feature compression responsible for the PCA sample segregation. Biologists and medical researchers often prefer effective methods that offer an immediate interpretation to complicated algorithms that in principle promise an improvement but in practice are difficult to be applied and interpreted. Here we present PC-corr: a simple algorithm that associates to any PCA segregation a discriminative network of features. Such network can be inspected in search of functional modules useful in the definition of combinatorial and multiscale biomarkers from multifaceted omic data in systems and precision biomedicine. We offer proofs of PC-corr efficacy on lipidomic, metagenomic, developmental genomic, population genetic, cancer promoteromic and cancer stem-cell mechanomic data. Finally, PC-corr is a general functional network inference approach that can be easily adopted for big data exploration in computer science and analysis of complex systems in physics. PMID:28287094

Supportive Family Environments Ameliorate the Link Between Racial Discrimination and Epigenetic Aging: A Replication Across Two Longitudinal Cohorts.

PubMed

Brody, Gene H; Miller, Gregory E; Yu, Tianyi; Beach, Steven R H; Chen, Edith

2016-04-01

This study tested the hypothesis that supportive family environments during adolescence buffer exposure to racial discrimination, reducing its impact on biological weathering and its manifestation in cellular aging. Perceived racial discrimination, support in the family environment, and confounder variables were assessed for 3 consecutive years across adolescence in two independent cohorts of African American youth from rural Georgia. DNA was extracted from peripheral blood mononuclear cells collected during young adulthood. Patterns of methylation were used to index the epigenetic ages of these cells and the extent to which they differed from participants' chronological ages. Among youth in supportive family environments, exposure to higher levels of racial discrimination did not forecast greater epigenetic aging. Among youth in less supportive family environments, exposure to higher levels of racial discrimination did forecast greater epigenetic aging. The associations emerged independently of confounder variables, and the results were replicated across the two cohorts. © The Author(s) 2016.

Supportive Family Environments Ameliorate the Link Between Racial Discrimination and Epigenetic Aging: A Replication Across Two Longitudinal Cohorts

PubMed Central

Brody, Gene H.; Miller, Gregory E.; Yu, Tianyi; Beach, Steven R. H.; Chen, Edith

2015-01-01

This study tested the hypothesis that supportive family environments during adolescence will buffer exposure to racial discrimination, reducing its impact on biological weathering and its manifestation in cellular aging. Indicators of racial discrimination, supportive family environments, and covariates were collected for 3 consecutive years across adolescence from 2 independent cohorts of African American youth from rural Georgia. DNA was extracted from peripheral blood mononuclear cells collected during young adulthood. Patterns of methylation were used to index epigenetic ages of these cells and the extent to which they differed from participants’ chronological ages. Among youth in supportive family environments, exposure to high levels of racial discrimination did not forecast epigenetic aging. Among youth in less supportive family environments, exposure to high levels of racial discrimination forecast faster epigenetic aging. The results did not change when confounder variables were included in the data analyses, and the results were replicated across cohorts. PMID:26917213

Enhancement of equivalence class formation by pretraining discriminative functions.

PubMed

Nartey, Richard K; Arntzen, Erik; Fields, Lanny

2015-03-01

The present experiment showed that a simple discriminative function acquired by an abstract stimulus through simultaneous and/or successive discrimination training enhanced the formation of an equivalence class of which that stimulus was a member. College students attempted to form three equivalence classes composed of three nodes and five members (A→B→C→D→E), using the simultaneous protocol. In the PIC group, the C stimuli were pictures and the A, B, D, and E stimuli were abstract shapes. In the ABS group, all of the stimuli were abstract shapes. In the SIM + SUCC (simultaneous and successive) group, simple discriminations were formed with the C stimuli through both simultaneous and successive discrimination training before class formation. Finally, in the SIM-only and SUCC-only groups, prior to class formation, simple discriminations were established for the C stimuli with a simultaneous procedure and a successive procedure, respectively. Equivalence classes were formed by 80% and 70% of the participants in the PIC and SIM + SUCC groups respectively, by 30% in the SUCC-only group, and by 10% apiece in the ABS and SIM-only groups. Thus, pretraining of combined simultaneous and successive discriminations enhanced class formation, as did the inclusion of a meaningful stimulus in a class. The isolated effect of forming successive discriminations was more influential than that of forming simultaneous discriminations. The establishment of both discriminations together produced an enhancement greater than the sum of the two procedures alone. Finally, a sorting test documented the maintenance of the classes formed during the simultaneous protocol. These results also provide a stimulus control-function account of the class-enhancing effects of meaningful stimuli.

New Bedform Phase Diagrams and Discriminant Functions for Formative Conditions of Bedforms in Open-Channel Flows

NASA Astrophysics Data System (ADS)

Ohata, Koji; Naruse, Hajime; Yokokawa, Miwa; Viparelli, Enrica

2017-11-01

Understanding of the formative conditions of fluvial bedforms is significant for both river management and geological studies. Diagrams showing bedform stability conditions have been widely used for the analyses of sedimentary structures. However, the use of discriminants to determine the boundaries of different bedforms regimes has not yet been explored. In this study, we use discriminant functions to describe formative conditions for a range of fluvial bedforms in a 3-D dimensionless parametric space. We do this by means of discriminant analysis using the Mahalanobis distance. We analyzed 3,793 available laboratory and field data and used these to produce new bedform phase diagrams. These diagrams employ three dimensionless parameters representing properties of flow hydraulics and sediment particles as their axes. The discriminant functions for bedform regimes proposed herein are quadratic functions of three dimensionless parameters and are expressed as curved surfaces in 3-D space. These empirical functions can be used to estimate paleoflow velocities from sedimentary structures. As an example of the reconstruction of hydraulic conditions, we calculated the paleoflow velocity of the 2011 Tohoku-Oki tsunami backwash flow from the sedimentary structures of the tsunami deposit. In so doing, we successfully reconstructed reasonable values of the paleoflow velocities.

Cyberbullying: The Discriminant Factors Among Cyberbullies, Cybervictims, and Cyberbully-Victims in a Czech Adolescent Sample.

PubMed

Bayraktar, Fatih; Machackova, Hana; Dedkova, Lenka; Cerna, Alena; Ševčíková, Anna

2015-11-01

Although the research on cyberbullying has increased dramatically in recent years, still little is known about how cyberbullying participant groups (i.e., cyberbullies, cybervictims, and cyberbully-victims) differ from one another. This study aims to discriminate between these groups at an individual and relational level by controlling for age and gender. Self-control, offline aggression, and self-esteem are analyzed as individual-level variables. Parental attachment and peer rejection are involved as relational-level variables. A total of 2,092 Czech adolescents aged 12 to 18 were enrolled from a random sample of 34 primary and secondary schools located in the South Moravian region of the Czech Republic. Discriminant function analyses indicated that the participant groups are discriminated by two functions. The first function increases the separation between cyberbullies and cyberbully-victims from cybervictims, indicating that cyberbullies and cyberbully-victims are similar to each other in terms of low self-control, offline aggression, and gender, and have higher scores on measures of low self-esteem and offline aggression. However, cyberbully-victims had the highest scores on these measures. The second function discriminates between all three groups, which indicates that those variables included in the second function (i.e., parental attachment, peer rejection, self-esteem, and age) distinguish all three involved groups. © The Author(s) 2014.

Discrimination and classification of acute lymphoblastic leukemia cells by Raman spectroscopy

NASA Astrophysics Data System (ADS)

Managò, Stefano; Valente, Carmen; Mirabelli, Peppino; De Luca, Anna Chiara

2015-05-01

Currently, a combination of technologies is typically required to identify and classify leukemia cells. These methods often lack the specificity and sensitivity necessary for early and accurate diagnosis. Here, we demonstrate the use of Raman spectroscopy to identify normal B cells, collected from healthy patients, and three ALL cell lines (RS4;11, REH and MN60 at different differentiation level, respectively). Raman markers associated with DNA and protein vibrational modes have been identified that exhibit excellent discriminating power for leukemia cell identification. Principal Component Analysis was finally used to confirm the significance of these markers for identify leukemia cells and classifying the data. The obtained results indicate a sorting accuracy of 96% between the three leukemia cell lines.

Retinal specialization through spatially varying cell densities and opsin coexpression in cichlid fish.

PubMed

Dalton, Brian E; de Busserolles, Fanny; Marshall, N Justin; Carleton, Karen L

2017-01-15

The distinct behaviours of animals and the varied habitats in which animals live place different requirements on their visual systems. A trade-off exists between resolution and sensitivity, with these properties varying across the retina. Spectral sensitivity, which affects both achromatic and chromatic (colour) vision, also varies across the retina, though the function of this inhomogeneity is less clear. We previously demonstrated spatially varying spectral sensitivity of double cones in the cichlid fish Metriaclima zebra owing to coexpression of different opsins. Here, we map the distributions of ganglion cells and cone cells and quantify opsin coexpression in single cones to show these also vary across the retina. We identify an area centralis with peak acuity and infrequent coexpression, which may be suited for tasks such as foraging and detecting male signals. The peripheral retina has reduced ganglion cell densities and increased opsin coexpression. Modeling of cichlid visual tasks indicates that coexpression might hinder colour discrimination of foraging targets and some fish colours. But, coexpression might improve contrast detection of dark objects against bright backgrounds, which might be useful for detecting predators or zooplankton. This suggests a trade-off between acuity and colour discrimination in the central retina versus lower resolution but more sensitive contrast detection in the peripheral retina. Significant variation in the pattern of coexpression among individuals, however, raises interesting questions about the selective forces at work. © 2017. Published by The Company of Biologists Ltd.

Body Composition of Elite Female Players in Five Different Sports Games

PubMed Central

Mala, Lucia; Maly, Tomas; Zahalka, František; Bunc, Vaclav; Kaplan, Ales; Jebavy, Radim; Tuma, Martin

2015-01-01

The goal of this study was to identify and compare body composition (BC) variables in elite female athletes (age ± years): volleyball (27.4 ± 4.1), softball (23.6 ± 4.9), basketball (25.9 ± 4.2), soccer (23.2 ± 4.2) and handball (24.0 ± 3.5) players. Fat-free mass (FFM), fat mass, percentage of fat mass (FMP), body cell mass (BCM), extracellular mass (ECM), their ratio, the percentage of BCM in FFM, the phase angle (α), and total body water, with a distinction between extracellular (ECW) and intracellular water, were measured using bioimpedance analysis. MANOVA showed significant differences in BC variables for athletes in different sports (F60.256 = 2.93, p < 0.01, η2 = 0.407). The results did not indicate any significant differences in FMP or α among the tested groups (p > 0.05). Significant changes in other BC variables were found in analyses when sport was used as an independent variable. Soccer players exhibited the most distinct BC, differing from players of other sports in 8 out of 10 variables. In contrast, the athletes with the most similar BC were volleyball and basketball players, who did not differ in any of the compared variables. Discriminant analysis revealed two significant functions (p < 0.01). The first discriminant function primarily represented differences based on the FFM proportion (volleyball, basketball vs. softball, soccer). The second discriminant function represented differences based on the ECW proportion (softball vs. soccer). Although all of the members of the studied groups competed at elite professional levels, significant differences in the selected BC variables were found. The results of the present study may serve as normative values for comparison or target values for training purposes. PMID:25964823

Body composition of elite female players in five different sports games.

PubMed

Mala, Lucia; Maly, Tomas; Zahalka, František; Bunc, Vaclav; Kaplan, Ales; Jebavy, Radim; Tuma, Martin

2015-03-29

The goal of this study was to identify and compare body composition (BC) variables in elite female athletes (age ± years): volleyball (27.4 ± 4.1), softball (23.6 ± 4.9), basketball (25.9 ± 4.2), soccer (23.2 ± 4.2) and handball (24.0 ± 3.5) players. Fat-free mass (FFM), fat mass, percentage of fat mass (FMP), body cell mass (BCM), extracellular mass (ECM), their ratio, the percentage of BCM in FFM, the phase angle (α), and total body water, with a distinction between extracellular (ECW) and intracellular water, were measured using bioimpedance analysis. MANOVA showed significant differences in BC variables for athletes in different sports (F60.256 = 2.93, p < 0.01, η2 = 0.407). The results did not indicate any significant differences in FMP or α among the tested groups (p > 0.05). Significant changes in other BC variables were found in analyses when sport was used as an independent variable. Soccer players exhibited the most distinct BC, differing from players of other sports in 8 out of 10 variables. In contrast, the athletes with the most similar BC were volleyball and basketball players, who did not differ in any of the compared variables. Discriminant analysis revealed two significant functions (p < 0.01). The first discriminant function primarily represented differences based on the FFM proportion (volleyball, basketball vs. softball, soccer). The second discriminant function represented differences based on the ECW proportion (softball vs. soccer). Although all of the members of the studied groups competed at elite professional levels, significant differences in the selected BC variables were found. The results of the present study may serve as normative values for comparison or target values for training purposes.

Merkel cells transduce and encode tactile stimuli to drive Aβ-afferent impulses

PubMed Central

Ikeda, Ryo; Cha, Myeounghoon; Ling, Jennifer; Jia, Zhanfeng; Coyle, Dennis; Gu, Jianguo G.

2014-01-01

SUMMARY Sensory systems for detecting tactile stimuli have evolved from touch-sensing nerves in invertebrates to complicated tactile end-organs in mammals. Merkel discs are tactile end-organs consisting of Merkel cells and Aβ-afferent nerve endings, and are localized in fingertips, whisker hair follicles and other touch-sensitive spots. Merkel discs transduce touch into slowly adapting impulses to enable tactile discrimination, but their transduction and encoding mechanisms remain unknown. Using rat whisker hair follicles, we show that Merkel cells rather than Aβ-afferent nerve endings are primary sites of tactile transduction, and identify the Piezo2 ion channel as the Merkel cell mechanical transducer. Piezo2 transduces tactile stimuli into Ca2+-action potentials in Merkel cells, which drive Aβ-afferent nerve endings to fire slowly adapting impulses. We further demonstrate that Piezo2 and Ca2+-action potentials in Merkel cells are required for behavioral tactile responses. Our findings provide insights into how tactile end-organs function and have clinical implications for tactile dysfunctions. PMID:24746027

Magnetic fingerprints of rolling cells for quantitative flow cytometry in whole blood

NASA Astrophysics Data System (ADS)

Reisbeck, Mathias; Helou, Michael Johannes; Richter, Lukas; Kappes, Barbara; Friedrich, Oliver; Hayden, Oliver

2016-09-01

Over the past 50 years, flow cytometry has had a profound impact on preclinical and clinical applications requiring single cell function information for counting, sub-typing and quantification of epitope expression. At the same time, the workflow complexity and high costs of such optical systems still limit flow cytometry applications to specialized laboratories. Here, we present a quantitative magnetic flow cytometer that incorporates in situ magnetophoretic cell focusing for highly accurate and reproducible rolling of the cellular targets over giant magnetoresistance sensing elements. Time-of-flight analysis is used to unveil quantitative single cell information contained in its magnetic fingerprint. Furthermore, we used erythrocytes as a biological model to validate our methodology with respect to precise analysis of the hydrodynamic cell diameter, quantification of binding capacity of immunomagnetic labels, and discrimination of cell morphology. The extracted time-of-flight information should enable point-of-care quantitative flow cytometry in whole blood for clinical applications, such as immunology and primary hemostasis.

Discrimination and quantification of autofluorescence spectra of human lung cells

NASA Astrophysics Data System (ADS)

Rahmani, Mahya; Khani, Mohammad Mehdi; Khazaei Koohpar, Zeinab; Molik, Paria

2016-10-01

To study laser-induced autofluorescence spectroscopy of the human lung cell line, we evaluated the native fluorescence properties of cancer QU-DB and normal MRC-5 human lung cells during continuous exposure to 405 nm laser light. Two emission bands centered at ~470 nm and ~560 nm were observed. These peaks are most likely attributable to mitochondrial fluorescent reduced nicotinamide adenine dinucleotide and riboflavin fluorophores, respectively. This article highlights lung cell autofluorescence characterization and signal discrimination by collective investigation of different spectral features. The absolute intensity, the spectral shape factor or redox ratio, the full width of half-maximum and the full width of quarter maximum was evaluated. Moreover, the intensity ratio, the area under the peak and the area ratio as a contrast factor for normal and cancerous cells were also calculated. Among all these features it seems that the contrast factor precisely and significantly discriminates the spectral differences of normal and cancerous lung cells. On the other hand, the relative quantum yield for both cell types were found by comparing the quantum yield of an unknown compound with known fluorescein sodium as a reference solution.

Perspectives for the treatment of sensorineural hearing loss by cellular regeneration of the inner ear.

PubMed

Almeida-Branco, Mario S; Cabrera, Sonia; Lopez-Escamez, Jose A

2015-01-01

Sensorineural hearing loss is a caused by the loss of the cochlear hair cells with the consequent deafferentation of spiral ganglion neurons. Humans do not show endogenous cellular regeneration in the inner ear and there is no exogenous therapy that allows the replacement of the damaged hair cells. Currently, treatment is based on the use of hearing aids and cochlear implants that present different outcomes, some difficulties in auditory discrimination and a limited useful life. More advanced technology is hindered by the functional capacity of the remaining spiral ganglion neurons. The latest advances with stem cell therapy and cellular reprogramming have developed several possibilities to induce endogenous regeneration or stem cell transplantation to replace damaged inner ear hair cells and restore hearing function. With further knowledge of the cellular and molecular biology of the inner ear and its embryonic development, it will be possible to use induced stem cells as in vitro models of disease and as replacement cellular therapy. Investigation in this area is focused on generating cellular therapy with clinical use for the treatment of profound sensorineural hearing loss. Copyright © 2014 Elsevier España, S.L.U. and Sociedad Española de Otorrinolaringología y Patología Cérvico-Facial. All rights reserved.

Characterization of Microbiota in Children with Chronic Functional Constipation

PubMed Central

de Meij, Tim G. J.; de Groot, Evelien F. J.; Eck, Anat; Budding, Andries E.; Kneepkens, C. M. Frank; Benninga, Marc A.; van Bodegraven, Adriaan A.; Savelkoul, Paul H. M.

2016-01-01

Objectives Disruption of the intestinal microbiota is considered an etiological factor in pediatric functional constipation. Scientifically based selection of potential beneficial probiotic strains in functional constipation therapy is not feasible due to insufficient knowledge of microbiota composition in affected subjects. The aim of this study was to describe microbial composition and diversity in children with functional constipation, compared to healthy controls. Study Design Fecal samples from 76 children diagnosed with functional constipation according to the Rome III criteria (median age 8.0 years; range 4.2–17.8) were analyzed by IS-pro, a PCR-based microbiota profiling method. Outcome was compared with intestinal microbiota profiles of 61 healthy children (median 8.6 years; range 4.1–17.9). Microbiota dissimilarity was depicted by principal coordinate analysis (PCoA), diversity was calculated by Shannon diversity index. To determine the most discriminative species, cross validated logistic ridge regression was performed. Results Applying total microbiota profiles (all phyla together) or per phylum analysis, no disease-specific separation was observed by PCoA and by calculation of diversity indices. By ridge regression, however, functional constipation and controls could be discriminated with 82% accuracy. Most discriminative species were Bacteroides fragilis, Bacteroides ovatus, Bifidobacterium longum, Parabacteroides species (increased in functional constipation) and Alistipes finegoldii (decreased in functional constipation). Conclusions None of the commonly used unsupervised statistical methods allowed for microbiota-based discrimination of children with functional constipation and controls. By ridge regression, however, both groups could be discriminated with 82% accuracy. Optimization of microbiota-based interventions in constipated children warrants further characterization of microbial signatures linked to clinical subgroups of functional constipation. PMID:27760208

Raman spectroscopic analysis of oral squamous cell carcinoma and oral dysplasia in the high-wavenumber region

NASA Astrophysics Data System (ADS)

Carvalho, Luis Felipe C. S.; Bonnier, Franck; O'Callaghan, Kate; O'Sullivan, Jeff; Flint, Stephen; Neto, Lazaro P. M.; Soto, Cláudio A. T.; dos Santos, Laurita; Martin, Airton A.; Byrne, Hugh J.; Lyng, Fiona M.

2015-06-01

Raman spectroscopy can provide a molecular-level signature of the biochemical composition and structure of cells with excellent spatial resolution and could be useful to monitor changes in composition for early stage and non-invasive cancer diagnosis, both ex-vivo and in vivo. In particular, the fingerprint spectral region (400-1,800 cm-1) has been shown to be very promising for optical biopsy purposes. However, limitations to discrimination of dysplastic and inflammatory processes based on the fingerprint region still persist. In addition, the Raman spectral signal of dysplastic cells is one important source of misdiagnosis of normal versus pathological tissues. The high wavenumber region (2,800-3,600 cm-1) provides more specific information based on N-H, O-H and C-H vibrations and can be used to identify the subtle changes which could be important for discrimination of samples. In this study, we demonstrate the potential of the highwavenumber spectral region by collecting Raman spectra of nucleoli, nucleus and cytoplasm from oral epithelial cancer (SCC-4) and dysplastic (DOK) cell lines and from normal oral epithelial primary cells, in vitro, which were then analyzed by area under the curve as a method to discriminate the spectra. In this region, we will show the discriminatory potential of the CH vibrational modes of nucleic acids, proteins and lipids. This technique demonstrated more efficient discrimination than the fingerprint region when we compared the cell cultures.

Deconstructing autofluorescence: non-invasive detection and monitoring of biochemistry in cells and tissues (Conference Presentation)

NASA Astrophysics Data System (ADS)

Goldys, Ewa M.; Gosnell, Martin E.; Anwer, Ayad G.; Cassano, Juan C.; Sue, Carolyn M.; Mahbub, Saabah B.; Pernichery, Sandeep M.; Inglis, David W.; Adhikary, Partho P.; Jazayeri, Jalal A.; Cahill, Michael A.; Saad, Sonia; Pollock, Carol; Sutton-Mcdowall, Melanie L.; Thompson, Jeremy G.

2016-03-01

Automated and unbiased methods of non-invasive cell monitoring able to deal with complex biological heterogeneity are fundamentally important for biology and medicine. Label-free cell imaging provides information about endogenous fluorescent metabolites, enzymes and cofactors in cells. However extracting high content information from imaging of native fluorescence has been hitherto impossible. Here, we quantitatively characterise cell populations in different tissue types, live or fixed, by using novel image processing and a simple multispectral upgrade of a wide-field fluorescence microscope. Multispectral intrinsic fluorescence imaging was applied to patient olfactory neurosphere-derived cells, cell model of a human metabolic disease MELAS (mitochondrial myopathy, encephalomyopathy, lactic acidosis, stroke-like syndrome). By using an endogenous source of contrast, subtle metabolic variations have been detected between living cells in their full morphological context which made it possible to distinguish healthy from diseased cells before and after therapy. Cellular maps of native fluorophores, flavins, bound and free NADH and retinoids unveiled subtle metabolic signatures and helped uncover significant cell subpopulations, in particular a subpopulation with compromised mitochondrial function. The versatility of our method is further illustrated by detecting genetic mutations in cancer, non-invasive monitoring of CD90 expression, label-free tracking of stem cell differentiation, identifying stem cell subpopulations with varying functional characteristics, tissue diagnostics in diabetes, and assessing the condition of preimplantation embryos. Our optimal discrimination approach enables statistical hypothesis testing and intuitive visualisations where previously undetectable differences become clearly apparent.

Diagnosing basal cell carcinoma in vivo by near-infrared Raman spectroscopy: a Principal Components Analysis discrimination algorithm

NASA Astrophysics Data System (ADS)

Silveira, Landulfo, Jr.; Silveira, Fabrício L.; Bodanese, Benito; Pacheco, Marcos Tadeu T.; Zângaro, Renato A.

2012-02-01

This work demonstrated the discrimination among basal cell carcinoma (BCC) and normal human skin in vivo using near-infrared Raman spectroscopy. Spectra were obtained in the suspected lesion prior resectional surgery. After tissue withdrawn, biopsy fragments were submitted to histopathology. Spectra were also obtained in the adjacent, clinically normal skin. Raman spectra were measured using a Raman spectrometer (830 nm) with a fiber Raman probe. By comparing the mean spectra of BCC with the normal skin, it has been found important differences in the 800-1000 cm-1 and 1250-1350 cm-1 (vibrations of C-C and amide III, respectively, from lipids and proteins). A discrimination algorithm based on Principal Components Analysis and Mahalanobis distance (PCA/MD) could discriminate the spectra of both tissues with high sensitivity and specificity.

Visual discrimination in the pigeon (Columba livia): effects of selective lesions of the nucleus rotundus

NASA Technical Reports Server (NTRS)

Laverghetta, A. V.; Shimizu, T.

1999-01-01

The nucleus rotundus is a large thalamic nucleus in birds and plays a critical role in many visual discrimination tasks. In order to test the hypothesis that there are functionally distinct subdivisions in the nucleus rotundus, effects of selective lesions of the nucleus were studied in pigeons. The birds were trained to discriminate between different types of stationary objects and between different directions of moving objects. Multiple regression analyses revealed that lesions in the anterior, but not posterior, division caused deficits in discrimination of small stationary stimuli. Lesions in neither the anterior nor posterior divisions predicted effects in discrimination of moving stimuli. These results are consistent with a prediction led from the hypothesis that the nucleus is composed of functional subdivisions.

[Discriminating power of socio-demographic and psychological variables on addictive use of cellular phones among middle school students].

PubMed

Lee, Haejung; Kim, Myoung Soo; Son, Hyun Kyung; Ahn, Sukhee; Kim, Jung Soon; Kim, Young Hae

2007-10-01

The purpose of this study was to examine the degrees of cellular phone usage among middle school students and to identify discriminating factors of addictive use of cellular phones among sociodemographic and psychological variables. From 123 middle schools in Busan, potential participants were identified through stratified random sampling and 747 middle school students participated in the study. The data was collected from December 1, 2004 to December 30, 2004. Descriptive and discriminant analyses were used. Fifty seven percent of the participants were male and 89.7% used cellular phones at school. The participants were grouped into three groups depending on the levels of the cellular phone usage: addicted (n=117), dependent (n=418), non-addicted (n=212). Within the three groups, two functions were produced and only one function was significant, discriminating the addiction group from non-addiction group. Additional discriminant analysis with only two groups produced one function that classified 81.2% of the participants correctly into the two groups. Impulsiveness, anxiety, and stress were significant discriminating factors. Based on the findings of this study, developing intervention programs focusing on impulsiveness, anxiety and stress to reduce the possible addictive use of cellular phones is suggested.

Low-dose sevoflurane promotes hippocampal neurogenesis and facilitates the development of dentate gyrus-dependent learning in neonatal rats.

PubMed

Chen, Chong; Shen, Feng-Yan; Zhao, Xuan; Zhou, Tao; Xu, Dao-Jie; Wang, Zhi-Ru; Wang, Ying-Wei

2015-01-01

Huge body of evidences demonstrated that volatile anesthetics affect the hippocampal neurogenesis and neurocognitive functions, and most of them showed impairment at anesthetic dose. Here, we investigated the effect of low dose (1.8%) sevoflurane on hippocampal neurogenesis and dentate gyrus-dependent learning. Neonatal rats at postnatal day 4 to 6 (P4-6) were treated with 1.8% sevoflurane for 6 hours. Neurogenesis was quantified by bromodeoxyuridine labeling and electrophysiology recording. Four and seven weeks after treatment, the Morris water maze and contextual-fear discrimination learning tests were performed to determine the influence on spatial learning and pattern separation. A 6-hour treatment with 1.8% sevoflurane promoted hippocampal neurogenesis and increased the survival of newborn cells and the proportion of immature granular cells in the dentate gyrus of neonatal rats. Sevoflurane-treated rats performed better during the training days of the Morris water maze test and in contextual-fear discrimination learning test. These results suggest that a subanesthetic dose of sevoflurane promotes hippocampal neurogenesis in neonatal rats and facilitates their performance in dentate gyrus-dependent learning tasks. © The Author(s) 2015.

Plasma-assisted quadruple-channel optosensing of proteins and cells with Mn-doped ZnS quantum dots.

PubMed

Li, Chenghui; Wu, Peng; Hou, Xiandeng

2016-02-21

Information extraction from nano-bio-systems is crucial for understanding their inner molecular level interactions and can help in the development of multidimensional/multimodal sensing devices to realize novel or expanded functionalities. The intrinsic fluorescence (IF) of proteins has long been considered as an effective tool for studying protein structures and dynamics, but not for protein recognition analysis partially because it generally contributes to the fluorescence background in bioanalysis. Here we explored the use of IF as the fourth channel optical input for a multidimensional optosensing device, together with the triple-channel optical output of Mn-doped ZnS QDs (fluorescence from ZnS host, phosphorescence from Mn(2+) dopant, and Rayleigh light scattering from the QDs), to dramatically improve the protein recognition and discrimination resolution. To further increase the cross-reactivity of the multidimensional optosensing device, plasma modification of proteins was explored to enhance the IF difference as well as their interactions with Mn-doped ZnS QDs. Such a sensor device was demonstrated for highly discriminative and precise identification of proteins in human serum and urine samples, and for cancer and normal cells as well.

HLA-E–restricted regulatory CD8+ T cells are involved in development and control of human autoimmune type 1 diabetes

PubMed Central

Jiang, Hong; Canfield, Steve M.; Gallagher, Mary P.; Jiang, Hong H.; Jiang, Yihua; Zheng, Zongyu; Chess, Leonard

2010-01-01

A key feature of the immune system is its ability to discriminate self from nonself. Breakdown in any of the mechanisms that maintain unresponsiveness to self (a state known as self-tolerance) contributes to the development of autoimmune conditions. Recent studies in mice show that CD8+ T cells specific for the unconventional MHC class I molecule Qa-1 bound to peptides derived from the signal sequence of Hsp60 (Hsp60sp) contribute to self/nonself discrimination. However, it is unclear whether they exist in humans and play a role in human autoimmune diseases. Here we have shown that CD8+ T cells specific for Hsp60sp bound to HLA-E (the human homolog of Qa-1) exist and play an important role in maintaining peripheral self-tolerance by discriminating self from nonself in humans. Furthermore, in the majority of type 1 diabetes (T1D) patients tested, there was a specific defect in CD8+ T cell recognition of HLA-E/Hsp60sp, which was associated with failure of self/nonself discrimination. However, the defect in the CD8+ T cells from most of the T1D patients tested could be corrected in vitro by exposure to autologous immature DCs loaded with the Hsp60sp peptide. These data suggest that HLA-E–restricted CD8+ T cells may play an important role in keeping self-reactive T cells in check. Thus, correction of this defect could be a potentially effective and safe approach in the therapy of T1D. PMID:20877010

[Discrimination of Rice Syrup Adulterant of Acacia Honey Based Using Near-Infrared Spectroscopy].

PubMed

Zhang, Yan-nan; Chen, Lan-zhen; Xue, Xiao-feng; Wu, Li-ming; Li, Yi; Yang, Juan

2015-09-01

At present, the rice syrup as a low price of the sweeteners was often adulterated into acacia honey and the adulterated honeys were sold in honey markets, while there is no suitable and fast method to identify honey adulterated with rice syrup. In this study, Near infrared spectroscopy (NIR) combined with chemometric methods were used to discriminate authenticity of honey. 20 unprocessed acacia honey samples from the different honey producing areas, mixed? with different proportion of rice syrup, were prepared of seven different concentration gradient? including 121 samples. The near infrared spectrum (NIR) instrument and spectrum processing software have been applied in the? spectrum? scanning and data conversion on adulterant samples, respectively. Then it was analyzed by Principal component analysis (PCA) and canonical discriminant analysis methods in order to discriminating adulterated honey. The results showed that after principal components analysis, the first two principal components accounted for 97.23% of total variation, but the regionalism of the score plot of the first two PCs was not obvious, so the canonical discriminant analysis was used to make the further discrimination, all samples had been discriminated correctly, the first two discriminant functions accounted for 91.6% among the six canonical discriminant functions, Then the different concentration of adulterant samples can be discriminated correctly, it illustrate that canonical discriminant analysis method combined with NIR spectroscopy is not only feasible but also practical for rapid and effective discriminate of the rice syrup adulterant of acacia honey.

Dendro-dendritic interactions between motion-sensitive large-field neurons in the fly.

PubMed

Haag, Juergen; Borst, Alexander

2002-04-15

For visual course control, flies rely on a set of motion-sensitive neurons called lobula plate tangential cells (LPTCs). Among these cells, the so-called CH (centrifugal horizontal) cells shape by their inhibitory action the receptive field properties of other LPTCs called FD (figure detection) cells specialized for figure-ground discrimination based on relative motion. Studying the ipsilateral input circuitry of CH cells by means of dual-electrode and combined electrical-optical recordings, we find that CH cells receive graded input from HS (large-field horizontal system) cells via dendro-dendritic electrical synapses. This particular wiring scheme leads to a spatial blur of the motion image on the CH cell dendrite, and, after inhibiting FD cells, to an enhancement of motion contrast. This could be crucial for enabling FD cells to discriminate object from self motion.

The quantal theory of how the immune system discriminates between "self and non-self"

PubMed

Smith, Kendall A

2004-12-17

In the past 50 years, immunologists have accumulated an amazing amount of information as to how the immune system functions. However, one of the most fundamental aspects of immunity, how the immune system discriminates between self vs. non-self, still remains an enigma. Any attempt to explain this most intriguing and fundamental characteristic must account for this decision at the level of the whole immune system, but as well, at the level of the individual cells making up the immune system. Moreover, it must provide for a molecular explanation as to how and why the cells behave as they do. The "Quantal Theory", proposed herein, is based upon the "Clonal Selection Theory", first proposed by Sir McFarland Burnet in 1955, in which he explained the remarkable specificity as well as diversity of recognition of everything foreign in the environment. The "Quantal Theory" is built upon Burnet's premise that after antigen selection of cell clones, a proliferative expansion of the selected cells ensues. Furthermore, it is derived from experiments which indicate that the proliferation of antigen-selected cell clones is determined by a quantal, "all-or-none", decision promulgated by a critical number of cellular receptors triggered by the T Cell Growth Factor (TCGF), interleukin 2 (IL2). An extraordinary number of experiments reported especially in the past 20 years, and detailed herein, indicate that the T cell Antigen Receptor (TCR) behaves similarly, and also that there are several critical numbers of triggered TCRs that determine different fates of the T cells. Moreover, the fates of the cells appear ultimately to be determined by the TCR triggering of the IL2 and IL2 receptor (IL2R) genes, which are also expressed in a very quantal fashion. The "Quantal Theory" states that the fundamental decisions of the T cell immune system are dependent upon the cells receiving a critical number of triggered TCRs and IL2Rs and that the cells respond in an all-or-none fashion. The "Quantal Theory" accounts fully for the development of T cells in the thymus, and such fundamental cellular fates as both "positive" and "negative" selection, as well as the decision to differentiate into a "Regulatory T cell" (T-Reg). In the periphery, the "Quantal Theory" accounts for the decision to proliferate or not in response to the presence of an antigen, either non-self or self, or to differentiate into a T-Reg. Since the immune system discriminates between self and non-self antigens by the accumulated number of triggered TCRs and IL2Rs, therapeutic manipulation of the determinants of these quantal decisions should permit new approaches to either enhance or dampen antigen-specific immune responses.

Discriminative functions and over-training as class-enhancing determinants of meaningful stimuli.

PubMed

Travis, Robert W; Fields, Lanny; Arntzen, Erik

2014-07-01

Likelihood of equivalence class formation (yield) was influenced by pre-class formation of simultaneous and successive discriminations, their mastery criteria, and overtraining of the successive discriminations. Each undergraduate in seven groups attempted to form two 3-node, 5-member equivalence classes (ABCDE). In the pictorial (PIC) group, meaningless nonsense syllables were used as the A, B, D, and E stimuli and meaningful pictures as the C stimuli. Nonsense syllables only were used in the other groups. The abstract (ABS) or 0-0-0 group involved no pre-class training. In the 84-0-0, 84-5-0 and 84-20-0 groups, simultaneous discriminations were trained among C stimuli to a mastery criterion of 84 trials, followed by successive discriminations trained to mastery criteria of 0, 5, and 20 trials, respectively. In the 84-20-0, 84-20-100, and 84-20-500 groups, simultaneous and successive discriminations were trained as noted, followed by overtraining with 0, 100, 500 successive-discrimination trials, respectively. The ABS group produced a 6% yield with the 84-0-0, 84-5-0, and 84-20-0 groups producing further modest increments. Overtraining produced a linear increase in yield, reaching 85% after 500 overtraining trials, a yield matching that produced by classes containing pictures as C stimuli (PIC). Thus, acquired discriminative functions and the overtraining of at least one function can account for class enhancement by meaningful stimuli. © Society for the Experimental Analysis of Behavior.

Discriminating the reaction types of plant type III polyketide synthases

PubMed Central

Shimizu, Yugo; Ogata, Hiroyuki; Goto, Susumu

2017-01-01

Abstract Motivation: Functional prediction of paralogs is challenging in bioinformatics because of rapid functional diversification after gene duplication events combined with parallel acquisitions of similar functions by different paralogs. Plant type III polyketide synthases (PKSs), producing various secondary metabolites, represent a paralogous family that has undergone gene duplication and functional alteration. Currently, there is no computational method available for the functional prediction of type III PKSs. Results: We developed a plant type III PKS reaction predictor, pPAP, based on the recently proposed classification of type III PKSs. pPAP combines two kinds of similarity measures: one calculated by profile hidden Markov models (pHMMs) built from functionally and structurally important partial sequence regions, and the other based on mutual information between residue positions. pPAP targets PKSs acting on ring-type starter substrates, and classifies their functions into four reaction types. The pHMM approach discriminated two reaction types with high accuracy (97.5%, 39/40), but its accuracy decreased when discriminating three reaction types (87.8%, 43/49). When combined with a correlation-based approach, all 49 PKSs were correctly discriminated, and pPAP was still highly accurate (91.4%, 64/70) even after adding other reaction types. These results suggest pPAP, which is based on linear discriminant analyses of similarity measures, is effective for plant type III PKS function prediction. Availability and Implementation: pPAP is freely available at ftp://ftp.genome.jp/pub/tools/ppap/ Contact: goto@kuicr.kyoto-u.ac.jp Supplementary information: Supplementary data are available at Bioinformatics online. PMID:28334262

REVERSAL LEARNING SET AND FUNCTIONAL EQUIVALENCE IN CHILDREN WITH AND WITHOUT AUTISM

PubMed Central

Lionello-DeNolf, Karen M.; McIlvane, William J.; Canovas, Daniela S.; de Souza, Deisy G.; Barros, Romariz S.

2009-01-01

To evaluate whether children with and without autism could exhibit (a) functional equivalence in the course of yoked repeated-reversal training and (b) reversal learning set, 6 children, in each of two experiments, were exposed to simple discrimination contingencies with three sets of stimuli. The discriminative functions of the set members were yoked and repeatedly reversed. In Experiment 1, all the children (of preschool age) showed gains in the efficiency of reversal learning across reversal problems and behavior that suggested formation of functional equivalence. In Experiment 2, 3 nonverbal children with autism exhibited strong evidence of reversal learning set and 2 showed evidence of functional equivalence. The data suggest a possible relationship between efficiency of reversal learning and functional equivalence test outcomes. Procedural variables may prove important in assessing the potential of young or nonverbal children to classify stimuli on the basis of shared discriminative functions. PMID:20186287

A micro-Raman spectroscopic investigation of leukemic U-937 cells in aged cultures

NASA Astrophysics Data System (ADS)

Fazio, Enza; Trusso, Sebastiano; Franco, Domenico; Nicolò, Marco Sebastiano; Allegra, Alessandro; Neri, Fortunato; Musolino, Caterina; Guglielmino, Salvatore P. P.

2016-04-01

Recently it has been shown that micro-Raman spectroscopy combined with multivariate analysis is able to discriminate among different types of tissues and tumoral cells by the detection of significant alterations and/or reorganizations of complex biological molecules, such as nucleic acids, lipids and proteins. Moreover, its use, being in principle a non-invasive technique, appears an interesting clinical tool for the evaluation of the therapeutical effects and of the disease progression. In this work we analyzed molecular changes in aged cultures of leukemia model U937 cells with respect to fresh cultures of the same cell line. In fact, structural variations of individual neoplastic cells on aging may lead to a heterogeneous data set, therefore falsifying confidence intervals, increasing error levels of analysis and consequently limiting the use of Raman spectroscopy analysis. We found that the observed morphological changes of U937 cells corresponded to well defined modifications of the Raman contributions in selected spectral regions, where markers of specific functional groups, useful to characterize the cell state, are present. A detailed subcellular analysis showed a change in cellular organization as a function of time, and correlated to a significant increase of apoptosis levels. Besides the aforementioned study, Raman spectra were used as input for principal component analysis (PCA) in order to detect and classify spectral changes among U937 cells.

Identification of microbes from the surfaces of food-processing lines based on the flow cytometric evaluation of cellular metabolic activity combined with cell sorting.

PubMed

Juzwa, W; Duber, A; Myszka, K; Białas, W; Czaczyk, K

2016-09-01

In this study the design of a flow cytometry-based procedure to facilitate the detection of adherent bacteria from food-processing surfaces was evaluated. The measurement of the cellular redox potential (CRP) of microbial cells was combined with cell sorting for the identification of microorganisms. The procedure enhanced live/dead cell discrimination owing to the measurement of the cell physiology. The microbial contamination of the surface of a stainless steel conveyor used to process button mushrooms was evaluated in three independent experiments. The flow cytometry procedure provided a step towards monitoring of contamination and enabled the assessment of microbial food safety hazards by the discrimination of active, mid-active and non-active bacterial sub-populations based on determination of their cellular vitality and subsequently single cell sorting to isolate microbial strains from discriminated sub-populations. There was a significant correlation (r = 0.97; p < 0.05) between the bacterial cell count estimated by the pour plate method and flow cytometry, despite there being differences in the absolute number of cells detected. The combined approach of flow cytometric CRP measurement and cell sorting allowed an in situ analysis of microbial cell vitality and the identification of species from defined sub-populations, although the identified microbes were limited to culturable cells.

Precise Quantitation of MicroRNA in a Single Cell with Droplet Digital PCR Based on Ligation Reaction.

PubMed

Tian, Hui; Sun, Yuanyuan; Liu, Chenghui; Duan, Xinrui; Tang, Wei; Li, Zhengping

2016-12-06

MicroRNA (miRNA) analysis in a single cell is extremely important because it allows deep understanding of the exact correlation between the miRNAs and cell functions. Herein, we wish to report a highly sensitive and precisely quantitative assay for miRNA detection based on ligation-based droplet digital polymerase chain reaction (ddPCR), which permits the quantitation of miRNA in a single cell. In this ligation-based ddPCR assay, two target-specific oligonucleotide probes can be simply designed to be complementary to the half-sequence of the target miRNA, respectively, which avoids the sophisticated design of reverse transcription and provides high specificity to discriminate a single-base difference among miRNAs with simple operations. After the miRNA-templated ligation, the ddPCR partitions individual ligated products into a water-in-oil droplet and digitally counts the fluorescence-positive and negative droplets after PCR amplification for quantification of the target molecules, which possesses the power of precise quantitation and robustness to variation in PCR efficiency. By integrating the advantages of the precise quantification of ddPCR and the simplicity of the ligation-based PCR, the proposed method can sensitively measure let-7a miRNA with a detection limit of 20 aM (12 copies per microliter), and even a single-base difference can be discriminated in let-7 family members. More importantly, due to its high selectivity and sensitivity, the proposed method can achieve precise quantitation of miRNAs in single-cell lysate. Therefore, the ligation-based ddPCR assay may serve as a useful tool to exactly reveal the miRNAs' actions in a single cell, which is of great importance for the study of miRNAs' biofunction as well as for the related biomedical studies.

Estimating a Logistic Discrimination Functions When One of the Training Samples Is Subject to Misclassification: A Maximum Likelihood Approach.

PubMed

Nagelkerke, Nico; Fidler, Vaclav

2015-01-01

The problem of discrimination and classification is central to much of epidemiology. Here we consider the estimation of a logistic regression/discrimination function from training samples, when one of the training samples is subject to misclassification or mislabeling, e.g. diseased individuals are incorrectly classified/labeled as healthy controls. We show that this leads to zero-inflated binomial model with a defective logistic regression or discrimination function, whose parameters can be estimated using standard statistical methods such as maximum likelihood. These parameters can be used to estimate the probability of true group membership among those, possibly erroneously, classified as controls. Two examples are analyzed and discussed. A simulation study explores properties of the maximum likelihood parameter estimates and the estimates of the number of mislabeled observations.

Cell-Based Odorant Sensor Array for Odor Discrimination Based on Insect Odorant Receptors.

PubMed

Termtanasombat, Maneerat; Mitsuno, Hidefumi; Misawa, Nobuo; Yamahira, Shinya; Sakurai, Takeshi; Yamaguchi, Satoshi; Nagamune, Teruyuki; Kanzaki, Ryohei

2016-07-01

The olfactory system of living organisms can accurately discriminate numerous odors by recognizing the pattern of activation of several odorant receptors (ORs). Thus, development of an odorant sensor array based on multiple ORs presents the possibility of mimicking biological odor discrimination mechanisms. Recently, we developed novel odorant sensor elements with high sensitivity and selectivity based on insect OR-expressing Sf21 cells that respond to target odorants by displaying increased fluorescence intensity. Here we introduce the development of an odorant sensor array composed of several Sf21 cell lines expressing different ORs. In this study, an array pattern of four cell lines expressing Or13a, Or56a, BmOR1, and BmOR3 was successfully created using a patterned polydimethylsiloxane film template and cell-immobilizing reagents, termed biocompatible anchor for membrane (BAM). We demonstrated that BAM could create a clear pattern of Sf21 sensor cells without impacting their odorant-sensing performance. Our sensor array showed odorant-specific response patterns toward both odorant mixtures and single odorant stimuli, allowing us to visualize the presence of 1-octen-3-ol, geosmin, bombykol, and bombykal as an increased fluorescence intensity in the region of Or13a, Or56a, BmOR1, and BmOR3 cell lines, respectively. Therefore, we successfully developed a new methodology for creating a cell-based odorant sensor array that enables us to discriminate multiple target odorants. Our method might be expanded into the development of an odorant sensor capable of detecting a large range of environmental odorants that might become a promising tool used in various applications including the study of insect semiochemicals and food contamination.

Mammalian Odor Information Recognition by Implanted Microsensor Array in vivo

NASA Astrophysics Data System (ADS)

Zhou, Jun; Dong, Qi; Zhuang, Liujing; Liu, Qingjun; Wang, Ping

2011-09-01

The mammalian olfactory system has an exquisite capacity to rapidly recognize and discriminate thousands of distinct odors in our environment. Our research group focus on reading information from olfactory bulb circuit of anethetized Sprague-Dawley rat and utilize artificial recognition system for odor discrimination. After being stimulated by three odors with concentration of 10 μM to rat nose, the response of mitral cells in olfactory bulb is recorded by eight channel microwire sensor array. In 20 sessions with 3 animals, we obtained 30 discriminated individual cells recordings. The average firing rates of the cells are Isoamyl acetate 26 Hz, Methoxybenzene 16 Hz, and Rose essential oil 11 Hz. By spike sorting, we detect peaks and analyze the interspike interval distribution. Further more, principal component analysis is applied to reduce the dimensionality of the data sets and classify the response.

Balancing specificity, sensitivity, and speed of ligand discrimination by zero-order ultraspecificity

NASA Astrophysics Data System (ADS)

Kajita, Masashi K.; Aihara, Kazuyuki; Kobayashi, Tetsuya J.

2017-07-01

Specific interactions between receptors and their target ligands in the presence of nontarget ligands are crucial for biological processes such as T cell ligand discrimination. To discriminate between the target and nontarget ligands, cells have to increase specificity to the target ligands by amplifying the small differences in affinity among ligands. In addition, sensitivity to the ligand concentration and quick discrimination are also important to detect low amounts of target ligands and facilitate fast cellular decision making after ligand recognition. In this work we propose a mechanism for nonlinear specificity amplification (ultraspecificity) based on zero-order saturating reactions, which was originally proposed to explain nonlinear sensitivity amplification (ultrasensitivity) to the ligand concentration. In contrast to the previously proposed proofreading mechanisms that amplify the specificity by a multistep reaction, our model can produce an optimal balance of specificity, sensitivity, and quick discrimination. Furthermore, we show that a model for insensitivity to a large number of nontarget ligands can be naturally derived from a model with the zero-order ultraspecificity. The zero-order ultraspecificity, therefore, may provide an alternative way to understand ligand discrimination from the viewpoint of nonlinear properties in biochemical reactions.

Sex determination from the talus and calcaneus measurements.

PubMed

Gualdi-Russo, Emanuela

2007-09-13

Several studies have demonstrated that discriminant function equations used to determine the sex of a skeleton are population-specific. The purpose of the present research was to develop discriminant function equations for sex determination on the basis of 18 variables on the right and left talus and calcaneus in a modern northern Italian sample. The sample consisted of 118 skeletons (62 males and 56 females) from the Frassetto Collection (University of Bologna). The ages of the individuals ranged from 19 to 70 years. The results indicated that metric traits of the talus (in particular) and calcaneus are good indicators of sexual dimorphism. The percentage of correct classification was high (87.9-95.7%). In view of the differences among current Italian populations, we tested the validity of the discriminant function equations in an independent sample of individuals of different origin (northern and southern Italy). The accuracy of classification was high only for the northern Italians. Most southern Italian males were misclassified as females, confirming the population-specificity of discriminant function equations.

When Is an Alveolar Type 2 Cell an Alveolar Type 2 Cell? A Conundrum for Lung Stem Cell Biology and Regenerative Medicine.

PubMed

Beers, Michael F; Moodley, Yuben

2017-07-01

Generating mature, differentiated, adult lung cells from pluripotent cells, such as induced pluripotent stem cells and embryonic stem cells, offers the hope of both generating disease-specific in vitro models and creating definitive and personalized therapies for a host of debilitating lung parenchymal and airway diseases. With the goal of advancing lung-regenerative medicine, several groups have developed and reported on protocols using defined media, coculture with mesenchymal components, or sequential treatments mimicking lung development, to obtain distal lung epithelial cells from stem cell precursors. However, there remains significant controversy about the degree of differentiation of these cells compared with their primary counterparts, coupled with a lack of consistency or uniformity in assessing the resultant phenotypes. Given the inevitable, exponential expansion of these approaches and the probable, but yet-to-emerge second and higher generation techniques to create such assets, we were prompted to pose the question, what makes a lung epithelial cell a lung epithelial cell? More specifically for this Perspective, we also posed the question, what are the minimum features that constitute an alveolar type (AT) 2 epithelial cell? In addressing this, we summarize a body of work spanning nearly five decades, amassed by a series of "lung epithelial cell biology pioneers," which carefully describes well characterized molecular, functional, and morphological features critical for discriminately assessing an AT2 phenotype. Armed with this, we propose a series of core criteria to assist the field in confirming that cells obtained following a differentiation protocol are indeed mature and functional AT2 epithelial cells.

Psychobiological impact of ethnic discrimination in Turkish immigrants living in Germany.

PubMed

Fischer, Susanne; Nater, Urs M; Strahler, Jana; Skoluda, Nadine; Dieterich, Leander; Oezcan, Orgun; Mewes, Ricarda

2017-03-01

Perceived ethnic discrimination has a negative impact on health. One of the key mechanisms may be a dysregulation of stress-responsive systems. Our aims were to investigate whether (1) acute face-to-face ethnic discrimination induces a stress response, and (2) to compare long-term endocrine functioning between immigrants and nonimmigrants. 30 male Turkish immigrants living in Germany underwent an ethnic discrimination condition and a control condition in the laboratory. Perceived ethnic discrimination, stress, salivary alpha-amylase and cortisol were measured four times. Heart rate and electrodermal activity were measured continuously. In addition, hair samples were collected from immigrants and 25 male nonimmigrants to determine long-term cortisol concentrations. Immigrants showed increases in perceived ethnic discrimination, stress, heart rate, alpha-amylase and cortisol during the ethnic discrimination condition. Immigrants had significantly lower hair cortisol concentrations than nonimmigrants. These findings suggest that acute ethnic discrimination elicits a psychobiological stress response. Abnormalities in long-term endocrine functioning in ethnic minorities may set the stage for the development of stress-related illnesses. Lay summary The present study found that racial discrimination of Turkish immigrants induced both psychological and physiological stress responses in the laboratory. Immigrants showed lower hair cortisol concentrations than nonimmigrants, indicating a dysregulated biological stress system.

Discrimination Power of Polynomial-Based Descriptors for Graphs by Using Functional Matrices.

PubMed

Dehmer, Matthias; Emmert-Streib, Frank; Shi, Yongtang; Stefu, Monica; Tripathi, Shailesh

2015-01-01

In this paper, we study the discrimination power of graph measures that are based on graph-theoretical matrices. The paper generalizes the work of [M. Dehmer, M. Moosbrugger. Y. Shi, Encoding structural information uniquely with polynomial-based descriptors by employing the Randić matrix, Applied Mathematics and Computation, 268(2015), 164-168]. We demonstrate that by using the new functional matrix approach, exhaustively generated graphs can be discriminated more uniquely than shown in the mentioned previous work.

Discrimination Power of Polynomial-Based Descriptors for Graphs by Using Functional Matrices

PubMed Central

Dehmer, Matthias; Emmert-Streib, Frank; Shi, Yongtang; Stefu, Monica; Tripathi, Shailesh

2015-01-01

In this paper, we study the discrimination power of graph measures that are based on graph-theoretical matrices. The paper generalizes the work of [M. Dehmer, M. Moosbrugger. Y. Shi, Encoding structural information uniquely with polynomial-based descriptors by employing the Randić matrix, Applied Mathematics and Computation, 268(2015), 164–168]. We demonstrate that by using the new functional matrix approach, exhaustively generated graphs can be discriminated more uniquely than shown in the mentioned previous work. PMID:26479495

Direct discriminant locality preserving projection with Hammerstein polynomial expansion.

PubMed

Chen, Xi; Zhang, Jiashu; Li, Defang

2012-12-01

Discriminant locality preserving projection (DLPP) is a linear approach that encodes discriminant information into the objective of locality preserving projection and improves its classification ability. To enhance the nonlinear description ability of DLPP, we can optimize the objective function of DLPP in reproducing kernel Hilbert space to form a kernel-based discriminant locality preserving projection (KDLPP). However, KDLPP suffers the following problems: 1) larger computational burden; 2) no explicit mapping functions in KDLPP, which results in more computational burden when projecting a new sample into the low-dimensional subspace; and 3) KDLPP cannot obtain optimal discriminant vectors, which exceedingly optimize the objective of DLPP. To overcome the weaknesses of KDLPP, in this paper, a direct discriminant locality preserving projection with Hammerstein polynomial expansion (HPDDLPP) is proposed. The proposed HPDDLPP directly implements the objective of DLPP in high-dimensional second-order Hammerstein polynomial space without matrix inverse, which extracts the optimal discriminant vectors for DLPP without larger computational burden. Compared with some other related classical methods, experimental results for face and palmprint recognition problems indicate the effectiveness of the proposed HPDDLPP.

Identification of Cell Cycle-Regulated Genes by Convolutional Neural Network.

PubMed

Liu, Chenglin; Cui, Peng; Huang, Tao

2017-01-01

The cell cycle-regulated genes express periodically with the cell cycle stages, and the identification and study of these genes can provide a deep understanding of the cell cycle process. Large false positives and low overlaps are big problems in cell cycle-regulated gene detection. Here, a computational framework called DLGene was proposed for cell cycle-regulated gene detection. It is based on the convolutional neural network, a deep learning algorithm representing raw form of data pattern without assumption of their distribution. First, the expression data was transformed to categorical state data to denote the changing state of gene expression, and four different expression patterns were revealed for the reported cell cycle-regulated genes. Then, DLGene was applied to discriminate the non-cell cycle gene and the four subtypes of cell cycle genes. Its performances were compared with six traditional machine learning methods. At last, the biological functions of representative cell cycle genes for each subtype are analyzed. Our method showed better and more balanced performance of sensitivity and specificity comparing to other machine learning algorithms. The cell cycle genes had very different expression pattern with non-cell cycle genes and among the cell-cycle genes, there were four subtypes. Our method not only detects the cell cycle genes, but also describes its expression pattern, such as when its highest expression level is reached and how it changes with time. For each type, we analyzed the biological functions of the representative genes and such results provided novel insight to the cell cycle mechanisms. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Segregation of Form, Color, Movement, and Depth: Anatomy, Physiology, and Perception

NASA Astrophysics Data System (ADS)

Livingstone, Margaret; Hubel, David

1988-05-01

Anatomical and physiological observations in monkeys indicate that the primate visual system consists of several separate and independent subdivisions that analyze different aspects of the same retinal image: cells in cortical visual areas 1 and 2 and higher visual areas are segregated into three interdigitating subdivisions that differ in their selectivity for color, stereopsis, movement, and orientation. The pathways selective for form and color seem to be derived mainly from the parvocellular geniculate subdivisions, the depth- and movement-selective components from the magnocellular. At lower levels, in the retina and in the geniculate, cells in these two subdivisions differ in their color selectivity, contrast sensitivity, temporal properties, and spatial resolution. These major differences in the properties of cells at lower levels in each of the subdivisions led to the prediction that different visual functions, such as color, depth, movement, and form perception, should exhibit corresponding differences. Human perceptual experiments are remarkably consistent with these predictions. Moreover, perceptual experiments can be designed to ask which subdivisions of the system are responsible for particular visual abilities, such as figure/ground discrimination or perception of depth from perspective or relative movement--functions that might be difficult to deduce from single-cell response properties.

Determining object orientation with a hierarchical database of binary synthetic discriminant function filters

NASA Technical Reports Server (NTRS)

Reid, Max B.; Ma, Paul W.; Downie, John D.

1990-01-01

An optical correlation-based system is demonstrated which recognizes an object and determines its angular orientation by traversing a hierarchical data base of binary filters. The data-base architecture is made possible by the development of binary synthetic discriminant function filters.

Motion coherence and direction discrimination in healthy aging.

PubMed

Pilz, Karin S; Miller, Louisa; Agnew, Hannah C

2017-01-01

Perceptual functions change with age, particularly motion perception. With regard to healthy aging, previous studies mostly measured motion coherence thresholds for coarse motion direction discrimination along cardinal axes of motion. Here, we investigated age-related changes in the ability to discriminate between small angular differences in motion directions, which allows for a more specific assessment of age-related decline and its underlying mechanisms. We first assessed older (>60 years) and younger (<30 years) participants' ability to discriminate coarse horizontal (left/right) and vertical (up/down) motion at 100% coherence and a stimulus duration of 400 ms. In a second step, we determined participants' motion coherence thresholds for vertical and horizontal coarse motion direction discrimination. In a third step, we used the individually determined motion coherence thresholds and tested fine motion direction discrimination for motion clockwise away from horizontal and vertical motion. Older adults performed as well as younger adults for discriminating motion away from vertical. Surprisingly, performance for discriminating motion away from horizontal was strongly decreased. Further analyses, however, showed a relationship between motion coherence thresholds for horizontal coarse motion direction discrimination and fine motion direction discrimination performance in older adults. In a control experiment, using motion coherence above threshold for all conditions, the difference in performance for horizontal and vertical fine motion direction discrimination for older adults disappeared. These results clearly contradict the notion of an overall age-related decline in motion perception, and, most importantly, highlight the importance of taking into account individual differences when assessing age-related changes in perceptual functions.

Energy metabolism of synaptosomes from different neuronal systems of rat cerebellum during aging: a functional proteomic characterization.

PubMed

Ferrari, Federica; Gorini, Antonella; Villa, Roberto Federico

2015-01-01

Functional proteomics was used to characterize age-related changes in energy metabolism of different neuronal pathways within the cerebellar cortex of Wistar rats aged 2, 6, 12, 18, and 24 months. The "large" synaptosomes, derived from the glutamatergic mossy fibre endings which make synaptic contact with the granule cells of the granular layer, and the "small" synaptosomes, derived from the pre-synaptic terminals of granule cells making synaptic contact with the dendrites of Purkinje cells, were isolated by a combined differential/gradient centrifugation technique. Because most brain disorders are associated with bioenergetic changes, the maximum rate (Vmax) of selected enzymes of glycolysis, Krebs' cycle, glutamate and amino acids metabolism, and acetylcholine catabolism were evaluated. The results show that "large" and "small" synaptosomes possess specific and independent metabolic features. This study represents a reliable model to study in vivo (1) the physiopathological molecular mechanisms of some brain diseases dependent on energy metabolism, (2) the responsiveness to noxious stimuli, and (3) the effects of drugs, discriminating their action sites at subcellular level on specific neuronal pathways.

Design of a highly selective quenched activity-based probe and its application in dual color imaging studies of cathepsin S activity localization.

PubMed

Oresic Bender, Kristina; Ofori, Leslie; van der Linden, Wouter A; Mock, Elliot D; Datta, Gopal K; Chowdhury, Somenath; Li, Hao; Segal, Ehud; Sanchez Lopez, Mateo; Ellman, Jonathan A; Figdor, Carl G; Bogyo, Matthew; Verdoes, Martijn

2015-04-15

The cysteine cathepsins are a group of 11 proteases whose function was originally believed to be the degradation of endocytosed material with a high degree of redundancy. However, it has become clear that these enzymes are also important regulators of both health and disease. Thus, selective tools that can discriminate between members of this highly related class of enzymes will be critical to further delineate the unique biological functions of individual cathepsins. Here we present the design and synthesis of a near-infrared quenched activity-based probe (qABP) that selectively targets cathepsin S which is highly expressed in immune cells. Importantly, this high degree of selectivity is retained both in vitro and in vivo. In combination with a new green-fluorescent pan-reactive cysteine cathepsin qABP we performed dual color labeling studies in bone marrow-derived immune cells and identified vesicles containing exclusively cathepsin S activity. This observation demonstrates the value of our complementary cathepsin probes and provides evidence for the existence of specific localization of cathepsin S activity in dendritic cells.

The tRNA methyltransferase Dnmt2 is required for accurate polypeptide synthesis during haematopoiesis.

PubMed

Tuorto, Francesca; Herbst, Friederike; Alerasool, Nader; Bender, Sebastian; Popp, Oliver; Federico, Giuseppina; Reitter, Sonja; Liebers, Reinhard; Stoecklin, Georg; Gröne, Hermann-Josef; Dittmar, Gunnar; Glimm, Hanno; Lyko, Frank

2015-09-14

The Dnmt2 enzyme utilizes the catalytic mechanism of eukaryotic DNA methyltransferases to methylate several tRNAs at cytosine 38. Dnmt2 mutant mice, flies, and plants were reported to be viable and fertile, and the biological function of Dnmt2 has remained elusive. Here, we show that endochondral ossification is delayed in newborn Dnmt2-deficient mice, which is accompanied by a reduction of the haematopoietic stem and progenitor cell population and a cell-autonomous defect in their differentiation. RNA bisulfite sequencing revealed that Dnmt2 methylates C38 of tRNA Asp(GTC), Gly(GCC), and Val(AAC), thus preventing tRNA fragmentation. Proteomic analyses from primary bone marrow cells uncovered systematic differences in protein expression that are due to specific codon mistranslation by tRNAs lacking Dnmt2-dependent methylation. Our observations demonstrate that Dnmt2 plays an important role in haematopoiesis and define a novel function of C38 tRNA methylation in the discrimination of near-cognate codons, thereby ensuring accurate polypeptide synthesis. © 2015 The Authors. Published under the terms of the CC BY NC ND 4.0 license.

A Differential Item Functional Analysis by Age of Perceived Interpersonal Discrimination in a Multi-racial/ethnic Sample of Adults.

PubMed

Owens, Sherry; Kristjansson, Alfgeir L; Hunte, Haslyn E R

2015-11-05

We investigated whether individual items on the nine item William's Perceived Everyday Discrimination Scale (EDS) functioned differently by age (<45 vs ≥ 45) within five racial groups in the United States: Asians (n=2,017); Hispanics (n=2,688); Black Caribbeans (n=1,377); African Americans (n=3,434); and Whites (n=854). We used data from the 2001-2003 National Survey of American Lives and the 2001-2003 National Latino and Asian Studies. Multiple-indicator, multiple-cause models (MIMIC) were used to examine differential item functioning (DIF) on the EDS by age within each racial/ethnic group. Overall, Asian and Hispanic respondents reported less discrimination than Whites; on the other hand, African Americans and Black Caribbeans reported more discrimination than Whites. Regardless of race/ethnicity, the younger respondents (aged <45 years) reported less discrimination than the older respondents (aged ≥ 45 years). In terms of age by race/ethnicity, the results were mixed for 19 out of 45 tests of DIF (40%). No differences in item function were observed among Black Caribbeans. "Being called names or insulted" and others acting as "if they are afraid" of the respondents were the only two items that did not exhibit differential item functioning by age across all racial/ethnic groups. Overall, our findings suggest that the EDS scale should be used with caution in multi-age multi-racial/ethnic samples.

Preoperative Beta Cell Function Is Predictive of Diabetes Remission After Bariatric Surgery.

PubMed

Souteiro, Pedro; Belo, Sandra; Neves, João Sérgio; Magalhães, Daniela; Silva, Rita Bettencourt; Oliveira, Sofia Castro; Costa, Maria Manuel; Saavedra, Ana; Oliveira, Joana; Cunha, Filipe; Lau, Eva; Esteves, César; Freitas, Paula; Varela, Ana; Queirós, Joana; Carvalho, Davide

2017-02-01

Bariatric surgery can improve glucose metabolism in obese patients with diabetes, but the factors that can predict diabetes remission are still under discussion. The present study aims to examine the impact of preoperative beta cell function on diabetes remission following surgery. We investigated a cohort of 363 obese diabetic patients who underwent bariatric surgery. The impact of several preoperative beta cell function indexes on diabetes remission was explored through bivariate logistic regression models. Postoperative diabetes remission was achieved in 39.9 % of patients. Younger patients (p < 0.001) and those with lower HbA1c (p = 0.001) at the baseline evaluation had higher odds of diabetes remission. Use of oral anti-diabetics and insulin therapy did not reach statistical significance when they were adjusted for age and HbA1c. Among the evaluated indexes of beta cell function, higher values of insulinogenix index, Stumvoll first- and second-phase indexes, fasting C-peptide, C-peptide area under the curve (AUC), C-peptide/glucose AUC, ISR (insulin secretion rate) AUC, and ISR/glucose AUC predicted diabetes remission even after adjustment for age and HbA1c. Among them, C-peptide AUC had the higher discriminative power (AUC 0.76; p < 0.001). Patients' age and preoperative HbA1c can forecast diabetes remission following surgery. Unlike other studies, our group found that the use of oral anti-diabetics and insulin therapy were not independent predictors of postoperative diabetes status. Preoperative beta cell function, mainly C-peptide AUC, is useful in predicting diabetes remission, and it should be assessed in all obese diabetic patients before bariatric or metabolic surgery.

Life satisfaction and trauma in clinical and non-clinical children living in a war-torn environment: A discriminant analysis.

PubMed

Veronese, Guido; Pepe, Alessandro

2017-07-01

The aim of this work was to discriminate between healthy children and children at risk of developing mental impairments by evaluating the impact on contextual and individual factors of a context characterized by war. We tested the hypothesis that a linear discriminant function composed of trauma, life satisfaction, and affect balance has the power to classify the children as community or clinical referred. Membership of the clinical-referred group was associated with poorer life satisfaction and higher levels of trauma. Community-referred profiles were associated with lesser trauma. Perceived life satisfaction regarding family and school was the main contributor to the discriminant function.

A novel gene expression-based prognostic scoring system to predict survival in gastric cancer

DOE PAGES

Wang, Pin; Wang, Yunshan; Hang, Bo; ...

2016-07-11

Analysis of gene expression patterns in gastric cancer (GC) can help to identify a comprehensive panel of gene biomarkers for predicting clinical outcomes and to discover potential new therapeutic targets. Here, a multi-step bioinformatics analytic approach was developed to establish a novel prognostic scoring system for GC. We first identified 276 genes that were robustly differentially expressed between normal and GC tissues, of which, 249 were found to be significantly associated with overall survival (OS) by univariate Cox regression analysis. The biological functions of 249 genes are related to cell cycle, RNA/ncRNA process, acetylation and extracellular matrix organization. A networkmore » was generated for view of the gene expression architecture of 249 genes in 265 GCs. Finally, we applied a canonical discriminant analysis approach to identify a 53-gene signature and a prognostic scoring system was established based on a canonical discriminant function of 53 genes. The prognostic scores strongly predicted patients with GC to have either a poor or good OS. Our study raises the prospect that the practicality of GC patient prognosis can be assessed by this prognostic scoring system.« less

A novel gene expression-based prognostic scoring system to predict survival in gastric cancer

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

Wang, Pin; Wang, Yunshan; Hang, Bo

Analysis of gene expression patterns in gastric cancer (GC) can help to identify a comprehensive panel of gene biomarkers for predicting clinical outcomes and to discover potential new therapeutic targets. Here, a multi-step bioinformatics analytic approach was developed to establish a novel prognostic scoring system for GC. We first identified 276 genes that were robustly differentially expressed between normal and GC tissues, of which, 249 were found to be significantly associated with overall survival (OS) by univariate Cox regression analysis. The biological functions of 249 genes are related to cell cycle, RNA/ncRNA process, acetylation and extracellular matrix organization. A networkmore » was generated for view of the gene expression architecture of 249 genes in 265 GCs. Finally, we applied a canonical discriminant analysis approach to identify a 53-gene signature and a prognostic scoring system was established based on a canonical discriminant function of 53 genes. The prognostic scores strongly predicted patients with GC to have either a poor or good OS. Our study raises the prospect that the practicality of GC patient prognosis can be assessed by this prognostic scoring system.« less

Dynamic functional brain networks involved in simple visual discrimination learning.

PubMed

Fidalgo, Camino; Conejo, Nélida María; González-Pardo, Héctor; Arias, Jorge Luis

2014-10-01

Visual discrimination tasks have been widely used to evaluate many types of learning and memory processes. However, little is known about the brain regions involved at different stages of visual discrimination learning. We used cytochrome c oxidase histochemistry to evaluate changes in regional brain oxidative metabolism during visual discrimination learning in a water-T maze at different time points during training. As compared with control groups, the results of the present study reveal the gradual activation of cortical (prefrontal and temporal cortices) and subcortical brain regions (including the striatum and the hippocampus) associated to the mastery of a simple visual discrimination task. On the other hand, the brain regions involved and their functional interactions changed progressively over days of training. Regions associated with novelty, emotion, visuo-spatial orientation and motor aspects of the behavioral task seem to be relevant during the earlier phase of training, whereas a brain network comprising the prefrontal cortex was found along the whole learning process. This study highlights the relevance of functional interactions among brain regions to investigate learning and memory processes. Copyright © 2014 Elsevier Inc. All rights reserved.

Shifts in color discrimination during early pregnancy.

PubMed

Orbán, Levente L; Dastur, Farhad N

2012-05-25

The present study explores two hypotheses: a) women during early pregnancy should experience increased color discrimination ability, and b) women during early pregnancy should experience shifts in subjective preference away from images of foods that appear either unripe or spoiled. Both of these hypotheses derive from an adaptive view of pregnancy sickness that proposes the function of pregnancy sickness is to decrease the likelihood of ingestion of foods with toxins or teratogens. Changes to color discrimination could be part of a network of perceptual and physiological defenses (e.g., changes to olfaction, nausea, vomiting) that support such a function. Participants included 13 pregnant women and 18 non-pregnant women. Pregnant women scored significantly higher than non-pregnant controls on the Farnsworth-Munsell (FM) 100 Hue Test, an objective test of color discrimination, although no difference was found between groups in preferences for food images at different stages of ripeness or spoilage. These results are the first indication that changes to color discrimination may occur during early pregnancy, and is consistent with the view that pregnancy sickness may function as an adaptive defense mechanism.

A Series of Zn(II) Terpyridine-Based Nitrate Complexes as Two-Photon Fluorescent Probe for Identifying Apoptotic and Living Cells via Subcellular Immigration.

PubMed

Liu, Dandan; Zhang, Mingzhu; Du, Wei; Hu, Lei; Li, Fei; Tian, Xiaohe; Wang, Aidong; Zhang, Qiong; Zhang, Zhongping; Wu, Jieying; Tian, Yupeng

2018-06-19

Two-photon active probe to label apoptotic cells plays a significant role in biological systems. However, discrimination of live/apoptotic cells at subcellular level under microscopy remains unachieved. Here, three novel Zn(II) terpyridine-based nitrate complexes (C1-C3) containing different pull/push units were designed. The structures of the ligands and their corresponding Zn(II) complexes were confirmed by single-crystal X-ray diffraction analysis. On the basis of the comprehensive comparison, C3 had a suitable two-photon absorption cross section in the near-infrared wavelength and good biocompatibility. Under two-photon confocal microscopy and transmission electron microscopy, it is found that C3 could target mitochondria in living cells but immigrate into the nucleolus during the apoptotic process. This dual-functional probe (C3) not only offers a valuable image tool but also acts as an indicator for cell mortality at subcellular level in a real-time manner.

Demonstration of the lack of cytotoxicity of unmodified and folic acid modified graphene oxide quantum dots, and their application to fluorescence lifetime imaging of HaCaT cells.

PubMed

Goreham, Renee V; Schroeder, Kathryn L; Holmes, Amy; Bradley, Siobhan J; Nann, Thomas

2018-01-24

The authors describe the synthesis of water-soluble and fluorescent graphene oxide quantum dots via acid exfoliation of graphite nanoparticles. The resultant graphene oxide quantum dots (GoQDs) were then modified with folic acid. Folic acid receptors are overexpressed in cancer cells and hence can bind to functionalized graphene oxide quantum dots. On excitation at 305 nm, the GoQDs display green fluorescence with a peak wavelength at ~520 nm. The modified GoQDs are non-toxic to macrophage cells even after prolonged exposure and high concentrations. Fluorescence lifetime imaging and multiphoton microscopy was used (in combination) to image HeCaT cells exposed to GoQDs, resulting in a superior method for bioimaging. Graphical abstract Schematic representation of graphene oxide quantum dots, folic acid modified graphene oxide quantum dots (red), and the use of fluorescence lifetime to discriminate against green auto-fluorescence of HeCaT cells.

Discrimination of bladder cancer cells from normal urothelial cells with high specificity and sensitivity: combined application of atomic force microscopy and modulated Raman spectroscopy.

PubMed

Canetta, Elisabetta; Riches, Andrew; Borger, Eva; Herrington, Simon; Dholakia, Kishan; Adya, Ashok K

2014-05-01

Atomic force microscopy (AFM) and modulated Raman spectroscopy (MRS) were used to discriminate between living normal human urothelial cells (SV-HUC-1) and bladder tumour cells (MGH-U1) with high specificity and sensitivity. MGH-U1 cells were 1.5-fold smaller, 1.7-fold thicker and 1.4-fold rougher than normal SV-HUC-1 cells. The adhesion energy was 2.6-fold higher in the MGH-U1 cells compared to normal SV-HUC-1 cells, which possibly indicates that bladder tumour cells are more deformable than normal cells. The elastic modulus of MGH-U1 cells was 12-fold lower than SV-HUC-1 cells, suggesting a higher elasticity of the bladder cancer cell membranes. The biochemical fingerprints of cancer cells displayed a higher DNA and lipid content, probably due to an increase in the nuclear to cytoplasm ratio. Normal cells were characterized by higher protein contents. AFM studies revealed a decrease in the lateral dimensions and an increase in thickness of cancer cells compared to normal cells; these studies authenticate the observations from MRS. Nanostructural, nanomechanical and biochemical profiles of bladder cells provide qualitative and quantitative markers to differentiate between normal and cancerous cells at the single cellular level. AFM and MRS allow discrimination between adhesion energy, elasticity and Raman spectra of SV-HUC-1 and MGH-U1 cells with high specificity (83, 98 and 95%) and sensitivity (97, 93 and 98%). Such single-cell-level studies could have a pivotal impact on the development of AFM-Raman combined methodologies for cancer profiling and screening with translational significance. Copyright © 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Passive microrheology of normal and cancer cells after ML7 treatment by atomic force microscopy

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

Lyapunova, Elena, E-mail: lyapunova@icmm.ru; Ural Federal University, Kuibyishev Str. 48, Ekaterinburg, 620000; Nikituk, Alexander, E-mail: nas@icmm.ru

Mechanical properties of living cancer and normal thyroidal cells were investigated by atomic force microscopy (AFM). Cell mechanics was compared before and after treatment with ML7, which is known to reduce myosin activity and induce softening of cell structures. We recorded force curves with extended dwell time of 6 seconds in contact at maximum forces from 500 pN to 1 nN. Data were analyzed within different frameworks: Hertz fit was applied in order to evaluate differences in Young’s moduli among cell types and conditions, while the fluctuations of the cantilever in contact with cells were analyzed with both conventional algorithmsmore » (probability density function and power spectral density) and multifractal detrended fluctuation analysis (MF-DFA). We found that cancer cells were softer than normal cells and ML7 had a substantial softening effect on normal cells, but only a marginal one on cancer cells. Moreover, we observed that all recorded signals for normal and cancer cells were monofractal with small differences between their scaling parameters. Finally, the applicability of wavelet-based methods of data analysis for the discrimination of different cell types is discussed.« less

A knowledge-based potential with an accurate description of local interactions improves discrimination between native and near-native protein conformations.

PubMed

Ferrada, Evandro; Vergara, Ismael A; Melo, Francisco

2007-01-01

The correct discrimination between native and near-native protein conformations is essential for achieving accurate computer-based protein structure prediction. However, this has proven to be a difficult task, since currently available physical energy functions, empirical potentials and statistical scoring functions are still limited in achieving this goal consistently. In this work, we assess and compare the ability of different full atom knowledge-based potentials to discriminate between native protein structures and near-native protein conformations generated by comparative modeling. Using a benchmark of 152 near-native protein models and their corresponding native structures that encompass several different folds, we demonstrate that the incorporation of close non-bonded pairwise atom terms improves the discriminating power of the empirical potentials. Since the direct and unbiased derivation of close non-bonded terms from current experimental data is not possible, we obtained and used those terms from the corresponding pseudo-energy functions of a non-local knowledge-based potential. It is shown that this methodology significantly improves the discrimination between native and near-native protein conformations, suggesting that a proper description of close non-bonded terms is important to achieve a more complete and accurate description of native protein conformations. Some external knowledge-based energy functions that are widely used in model assessment performed poorly, indicating that the benchmark of models and the specific discrimination task tested in this work constitutes a difficult challenge.

Suppression of Lymphocyte Functions by Plasma Exosomes Correlates with Disease Activity in Patients with Head and Neck Cancer.

PubMed

Ludwig, Sonja; Floros, Theofanis; Theodoraki, Marie-Nicole; Hong, Chang-Sook; Jackson, Edwin K; Lang, Stephan; Whiteside, Theresa L

2017-08-15

Purpose: Head and neck cancers (HNCs) often induce profound immunosuppression, which contributes to disease progression and interferes with immune-based therapies. Body fluids of patients with HNC are enriched in exosomes potentially engaged in negative regulation of antitumor immune responses. The presence and content of exosomes derived from plasma of patients with HNC are evaluated for the ability to induce immune dysfunction and influence disease activity. Experimental Design: Exosomes were isolated by size-exclusion chromatography from plasma of 38 patients with HNC and 14 healthy donors. Morphology, size, numbers, and protein and molecular contents of the recovered exosomes were determined. Coculture assays were performed to measure exosome-mediated effects on functions of normal human lymphocyte subsets and natural killer (NK) cells. The results were correlated with disease stage and activity. Results: The presence, quantity, and molecular content of isolated, plasma-derived exosomes discriminated patients with HNC with active disease (AD) from those with no evident disease (NED) after oncologic therapies. Exosomes of patients with AD were significantly more effective than exosomes of patients with NED in inducing apoptosis of CD8 + T cells, suppression of CD4 + T-cell proliferation, and upregulation of regulatory T-cell (Treg) suppressor functions (all at P < 0.05). Exosomes of patients with AD also downregulated NKG2D expression levels in NK cells. Conclusions: Exosomes in plasma of patients with HNC carry immunosuppressive molecules and interfere with functions of immune cells. Exosome-induced immune suppression correlates with disease activity in HNC, suggesting that plasma exosomes could be useful as biomarkers of HNC progression. Clin Cancer Res; 23(16); 4843-54. ©2017 AACR . ©2017 American Association for Cancer Research.

[Study on the classification of dominant pathogens related to febrile respiratory syndrome, based on the method of Bayes discriminant analysis].

PubMed

Li, X C; Li, J S; Meng, L; Bai, Y N; Yu, D S; Liu, X N; Liu, X F; Jiang, X J; Ren, X W; Yang, X T; Shen, X P; Zhang, J W

2017-08-10

Objective: To understand the dominant pathogens of febrile respiratory syndrome (FRS) patients in Gansu province and to establish the Bayes discriminant function in order to identify the patients infected with the dominant pathogens. Methods: FRS patients were collected in various sentinel hospitals of Gansu province from 2009 to 2015 and the dominant pathogens were determined by describing the composition of pathogenic profile. Significant clinical variables were selected by stepwise discriminant analysis to establish the Bayes discriminant function. Results: In the detection of pathogens for FRS, both influenza virus and rhinovirus showed higher positive rates than those caused by other viruses (13.79%, 8.63%), that accounting for 54.38%, 13.73% of total viral positive patients. Most frequently detected bacteria would include Streptococcus pneumoniae , and haemophilus influenza (44.41%, 18.07%) that accounting for 66.21% and 24.55% among the bacterial positive patients. The original-validated rate of discriminant function, established by 11 clinical variables, was 73.1%, with the cross-validated rate as 70.6%. Conclusion: Influenza virus, Rhinovirus, Streptococcus pneumoniae and Haemophilus influenzae were the dominant pathogens of FRS in Gansu province. Results from the Bayes discriminant analysis showed both higher accuracy in the classification of dominant pathogens, and applicative value for FRS.

SChloro: directing Viridiplantae proteins to six chloroplastic sub-compartments.

PubMed

Savojardo, Castrense; Martelli, Pier Luigi; Fariselli, Piero; Casadio, Rita

2017-02-01

Chloroplasts are organelles found in plants and involved in several important cell processes. Similarly to other compartments in the cell, chloroplasts have an internal structure comprising several sub-compartments, where different proteins are targeted to perform their functions. Given the relation between protein function and localization, the availability of effective computational tools to predict protein sub-organelle localizations is crucial for large-scale functional studies. In this paper we present SChloro, a novel machine-learning approach to predict protein sub-chloroplastic localization, based on targeting signal detection and membrane protein information. The proposed approach performs multi-label predictions discriminating six chloroplastic sub-compartments that include inner membrane, outer membrane, stroma, thylakoid lumen, plastoglobule and thylakoid membrane. In comparative benchmarks, the proposed method outperforms current state-of-the-art methods in both single- and multi-compartment predictions, with an overall multi-label accuracy of 74%. The results demonstrate the relevance of the approach that is eligible as a good candidate for integration into more general large-scale annotation pipelines of protein subcellular localization. The method is available as web server at http://schloro.biocomp.unibo.it gigi@biocomp.unibo.it.

Targeted sorting of single virus-infected cells of the coccolithophore Emiliania huxleyi.

PubMed

Martínez Martínez, Joaquín; Poulton, Nicole J; Stepanauskas, Ramunas; Sieracki, Michael E; Wilson, William H

2011-01-01

Discriminating infected from healthy cells is the first step to understanding the mechanisms and ecological implications of viral infection. We have developed a method for detecting, sorting, and performing molecular analysis of individual, infected cells of the important microalga Emiliania huxleyi, based on known physiological responses to viral infection. Of three fluorescent dyes tested, FM 1-43 (for detecting membrane blebbing) gave the most unequivocal and earliest separation of cells. Furthermore, we were able to amplify the genomes of single infected cells using Multiple Displacement Amplification. This novel method to reliably discriminate infected from healthy cells in cultures will allow researchers to answer numerous questions regarding the mechanisms and implications of viral infection of E. huxleyi. The method may be transferable to other virus-host systems.

Mining for class-specific motifs in protein sequence classification

PubMed Central

2013-01-01

Background In protein sequence classification, identification of the sequence motifs or n-grams that can precisely discriminate between classes is a more interesting scientific question than the classification itself. A number of classification methods aim at accurate classification but fail to explain which sequence features indeed contribute to the accuracy. We hypothesize that sequences in lower denominations (n-grams) can be used to explore the sequence landscape and to identify class-specific motifs that discriminate between classes during classification. Discriminative n-grams are short peptide sequences that are highly frequent in one class but are either minimally present or absent in other classes. In this study, we present a new substitution-based scoring function for identifying discriminative n-grams that are highly specific to a class. Results We present a scoring function based on discriminative n-grams that can effectively discriminate between classes. The scoring function, initially, harvests the entire set of 4- to 8-grams from the protein sequences of different classes in the dataset. Similar n-grams of the same size are combined to form new n-grams, where the similarity is defined by positive amino acid substitution scores in the BLOSUM62 matrix. Substitution has resulted in a large increase in the number of discriminatory n-grams harvested. Due to the unbalanced nature of the dataset, the frequencies of the n-grams are normalized using a dampening factor, which gives more weightage to the n-grams that appear in fewer classes and vice-versa. After the n-grams are normalized, the scoring function identifies discriminative 4- to 8-grams for each class that are frequent enough to be above a selection threshold. By mapping these discriminative n-grams back to the protein sequences, we obtained contiguous n-grams that represent short class-specific motifs in protein sequences. Our method fared well compared to an existing motif finding method known as Wordspy. We have validated our enriched set of class-specific motifs against the functionally important motifs obtained from the NLSdb, Prosite and ELM databases. We demonstrate that this method is very generic; thus can be widely applied to detect class-specific motifs in many protein sequence classification tasks. Conclusion The proposed scoring function and methodology is able to identify class-specific motifs using discriminative n-grams derived from the protein sequences. The implementation of amino acid substitution scores for similarity detection, and the dampening factor to normalize the unbalanced datasets have significant effect on the performance of the scoring function. Our multipronged validation tests demonstrate that this method can detect class-specific motifs from a wide variety of protein sequence classes with a potential application to detecting proteome-specific motifs of different organisms. PMID:23496846

A Functional and Regulatory Network Associated with PIP Expression in Human Breast Cancer

PubMed Central

Debily, Marie-Anne; Marhomy, Sandrine El; Boulanger, Virginie; Eveno, Eric; Mariage-Samson, Régine; Camarca, Alessandra; Auffray, Charles; Piatier-Tonneau, Dominique; Imbeaud, Sandrine

2009-01-01

Background The PIP (prolactin-inducible protein) gene has been shown to be expressed in breast cancers, with contradictory results concerning its implication. As both the physiological role and the molecular pathways in which PIP is involved are poorly understood, we conducted combined gene expression profiling and network analysis studies on selected breast cancer cell lines presenting distinct PIP expression levels and hormonal receptor status, to explore the functional and regulatory network of PIP co-modulated genes. Principal Findings Microarray analysis allowed identification of genes co-modulated with PIP independently of modulations resulting from hormonal treatment or cell line heterogeneity. Relevant clusters of genes that can discriminate between [PIP+] and [PIP−] cells were identified. Functional and regulatory network analyses based on a knowledge database revealed a master network of PIP co-modulated genes, including many interconnecting oncogenes and tumor suppressor genes, half of which were detected as differentially expressed through high-precision measurements. The network identified appears associated with an inhibition of proliferation coupled with an increase of apoptosis and an enhancement of cell adhesion in breast cancer cell lines, and contains many genes with a STAT5 regulatory motif in their promoters. Conclusions Our global exploratory approach identified biological pathways modulated along with PIP expression, providing further support for its good prognostic value of disease-free survival in breast cancer. Moreover, our data pointed to the importance of a regulatory subnetwork associated with PIP expression in which STAT5 appears as a potential transcriptional regulator. PMID:19262752

The microRNA Expression Profile in Donation after Cardiac Death (DCD) Livers and Its Ability to Identify Primary Non Function.

PubMed

Khorsandi, Shirin Elizabeth; Quaglia, Alberto; Salehi, Siamak; Jassem, Wayel; Vilca-Melendez, Hector; Prachalias, Andreas; Srinivasan, Parthi; Heaton, Nigel

2015-01-01

Donation after cardiac death (DCD) livers are marginal organs for transplant and their use is associated with a higher risk of primary non function (PNF) or early graft dysfunction (EGD). The aim was to determine if microRNA (miRNA) was able to discriminate between DCD livers of varying clinical outcome. DCD groups were categorized as PNF retransplanted within a week (n=7), good functional outcome (n=7) peak aspartate transaminase (AST) ≤ 1000 IU/L and EGD (n=9) peak AST ≥ 2500 IU/L. miRNA was extracted from archival formalin fixed post-perfusion tru-cut liver biopsies. High throughput expression analysis was performed using miRNA arrays. Bioinformatics for expression data analysis was performed and validated with real time quantitative PCR (RT-qPCR). The function of miRNA of interest was investigated using computational biology prediction algorithms. From the array analysis 16 miRNAs were identified as significantly different (p<0.05). On RT-qPCR miR-155 and miR-940 had the highest expression across all three DCD clinical groups. Only one miRNA, miR-22, was validated with marginal significance, to have differential expression between the three groups (p=0.049). From computational biology miR-22 was predicted to affect signalling pathways that impact protein turnover, metabolism and apoptosis/cell cycle. In conclusion, microRNA expression patterns have a low diagnostic potential clinically in discriminating DCD liver quality and outcome.

Ensemble-Based Computational Approach Discriminates Functional Activity of p53 Cancer and Rescue Mutants

PubMed Central

Demir, Özlem; Baronio, Roberta; Salehi, Faezeh; Wassman, Christopher D.; Hall, Linda; Hatfield, G. Wesley; Chamberlin, Richard; Kaiser, Peter; Lathrop, Richard H.; Amaro, Rommie E.

2011-01-01

The tumor suppressor protein p53 can lose its function upon single-point missense mutations in the core DNA-binding domain (“cancer mutants”). Activity can be restored by second-site suppressor mutations (“rescue mutants”). This paper relates the functional activity of p53 cancer and rescue mutants to their overall molecular dynamics (MD), without focusing on local structural details. A novel global measure of protein flexibility for the p53 core DNA-binding domain, the number of clusters at a certain RMSD cutoff, was computed by clustering over 0.7 µs of explicitly solvated all-atom MD simulations. For wild-type p53 and a sample of p53 cancer or rescue mutants, the number of clusters was a good predictor of in vivo p53 functional activity in cell-based assays. This number-of-clusters (NOC) metric was strongly correlated (r2 = 0.77) with reported values of experimentally measured ΔΔG protein thermodynamic stability. Interpreting the number of clusters as a measure of protein flexibility: (i) p53 cancer mutants were more flexible than wild-type protein, (ii) second-site rescue mutations decreased the flexibility of cancer mutants, and (iii) negative controls of non-rescue second-site mutants did not. This new method reflects the overall stability of the p53 core domain and can discriminate which second-site mutations restore activity to p53 cancer mutants. PMID:22028641

Cell nuclei segmentation in fluorescence microscopy images using inter- and intra-region discriminative information.

PubMed

Song, Yang; Cai, Weidong; Feng, David Dagan; Chen, Mei

2013-01-01

Automated segmentation of cell nuclei in microscopic images is critical to high throughput analysis of the ever increasing amount of data. Although cell nuclei are generally visually distinguishable for human, automated segmentation faces challenges when there is significant intensity inhomogeneity among cell nuclei or in the background. In this paper, we propose an effective method for automated cell nucleus segmentation using a three-step approach. It first obtains an initial segmentation by extracting salient regions in the image, then reduces false positives using inter-region feature discrimination, and finally refines the boundary of the cell nuclei using intra-region contrast information. This method has been evaluated on two publicly available datasets of fluorescence microscopic images with 4009 cells, and has achieved superior performance compared to popular state of the art methods using established metrics.

Mining HIV protease cleavage data using genetic programming with a sum-product function.

PubMed

Yang, Zheng Rong; Dalby, Andrew R; Qiu, Jing

2004-12-12

In order to design effective HIV inhibitors, studying and understanding the mechanism of HIV protease cleavage specification is critical. Various methods have been developed to explore the specificity of HIV protease cleavage activity. However, success in both extracting discriminant rules and maintaining high prediction accuracy is still challenging. The earlier study had employed genetic programming with a min-max scoring function to extract discriminant rules with success. However, the decision will finally be degenerated to one residue making further improvement of the prediction accuracy difficult. The challenge of revising the min-max scoring function so as to improve the prediction accuracy motivated this study. This paper has designed a new scoring function called a sum-product function for extracting HIV protease cleavage discriminant rules using genetic programming methods. The experiments show that the new scoring function is superior to the min-max scoring function. The software package can be obtained by request to Dr Zheng Rong Yang.

Constant versus variable response signal delays in speed--accuracy trade-offs: effects of advance preparation for processing time.

PubMed

Miller, Jeff; Sproesser, Gudrun; Ulrich, Rolf

2008-07-01

In two experiments, we used response signals (RSs) to control processing time and trace out speed--accuracy trade-off(SAT) functions in a difficult perceptual discrimination task. Each experiment compared performance in blocks of trials with constant and, hence, temporally predictable RS lags against performance in blocks with variable, unpredictable RS lags. In both experiments, essentially equivalent SAT functions were observed with constant and variable RS lags. We conclude that there is little effect of advance preparation for a given processing time, suggesting that the discrimination mechanisms underlying SAT functions are driven solely by bottom-up information processing in perceptual discrimination tasks.

The Discriminating Power of Items that Measure More than One Dimension.

ERIC Educational Resources Information Center

Reckase, Mark D.

The work presented in this paper defined conceptually the concepts of multidimensional discrimination and information, derived mathematical expressions for the concepts for a particular multidimensional item response theory (IRT) model, and applied the concepts to actual test data. Multidimensional discrimination was defined as a function of the…

Neural Correlates of Infant Accent Discrimination: An fNIRS Study

ERIC Educational Resources Information Center

Cristia, Alejandrina; Minagawa-Kawai, Yasuyo; Egorova, Natalia; Gervain, Judit; Filippin, Luca; Cabrol, Dominique; Dupoux, Emmanuel

2014-01-01

The present study investigated the neural correlates of infant discrimination of very similar linguistic varieties (Quebecois and Parisian French) using functional Near InfraRed Spectroscopy. In line with previous behavioral and electrophysiological data, there was no evidence that 3-month-olds discriminated the two regional accents, whereas…

Computer vision approach to morphometric feature analysis of basal cell nuclei for evaluating malignant potentiality of oral submucous fibrosis.

PubMed

Muthu Rama Krishnan, M; Pal, Mousumi; Paul, Ranjan Rashmi; Chakraborty, Chandan; Chatterjee, Jyotirmoy; Ray, Ajoy K

2012-06-01

This research work presents a quantitative approach for analysis of histomorphometric features of the basal cell nuclei in respect to their size, shape and intensity of staining, from surface epithelium of Oral Submucous Fibrosis showing dysplasia (OSFD) to that of the Normal Oral Mucosa (NOM). For all biological activity, the basal cells of the surface epithelium form the proliferative compartment and therefore their morphometric changes will spell the intricate biological behavior pertaining to normal cellular functions as well as in premalignant and malignant status. In view of this, the changes in shape, size and intensity of staining of the nuclei in the basal cell layer of the NOM and OSFD have been studied. Geometric, Zernike moments and Fourier descriptor (FD) based as well as intensity based features are extracted for histomorphometric pattern analysis of the nuclei. All these features are statistically analyzed along with 3D visualization in order to discriminate the groups. Results showed increase in the dimensions (area and perimeter), shape parameters and decreasing mean nuclei intensity of the nuclei in OSFD in respect to NOM. Further, the selected features are fed to the Bayesian classifier to discriminate normal and OSFD. The morphometric and intensity features provide a good sensitivity of 100%, specificity of 98.53% and positive predicative accuracy of 97.35%. This comparative quantitative characterization of basal cell nuclei will be of immense help for oral onco-pathologists, researchers and clinicians to assess the biological behavior of OSFD, specially relating to their premalignant and malignant potentiality. As a future direction more extensive study involving more number of disease subjects is observed.

Differentiation of different mixed Listeria strains and also acid-injured, heat-injured, and repaired cells of Listeria monocytogenes using fourier transform infrared spectroscopy.

PubMed

Nyarko, Esmond; Donnelly, Catherine

2015-03-01

Fourier transform infrared (FT-IR) spectroscopy was used to differentiate mixed strains of Listeria monocytogenes and mixed strains of L. monocytogenes and Listeria innocua. FT-IR spectroscopy was also applied to investigate the hypothesis that heat-injured and acid-injured cells would return to their original physiological integrity following repair. Thin smears of cells on infrared slides were prepared from cultures for mixed strains of L. monocytogenes, mixed strains of L. monocytogenes and L. innocua, and each individual strain. Heat-injured and acid-injured cells were prepared by exposing harvested cells of L. monocytogenes strain R2-764 to a temperature of 56 ± 0.2°C for 10 min or lactic acid at pH 3 for 60 min, respectively. Cellular repair involved incubating aliquots of acid-injured and heat-injured cells separately in Trypticase soy broth supplemented with 0.6% yeast extract for 22 to 24 h; bacterial thin smears on infrared slides were prepared for each treatment. Spectral collection was done using 250 scans at a resolution of 4 cm(-1) in the mid-infrared wavelength region. Application of multivariate discriminant analysis to the wavelength region from 1,800 to 900 cm(-1) separated the individual L. monocytogenes strains. Mixed strains of L. monocytogenes and L. monocytogenes cocultured with L. innocua were successfully differentiated from the individual strains when the discriminant analysis was applied. Different mixed strains of L. monocytogenes were also successfully separated when the discriminant analysis was applied. A data set for injury and repair analysis resulted in the separation of acid-injured, heat-injured, and intact cells; repaired cells clustered closer to intact cells when the discriminant analysis (1,800 to 600 cm(-1)) was applied. FT-IR spectroscopy can be used for the rapid source tracking of L. monocytogenes strains because it can differentiate between different mixed strains and individual strains of the pathogen.

Olfactory discrimination ability of CD-1 mice for a large array of enantiomers.

PubMed

Laska, M; Shepherd, G M

2007-01-05

With use of a conditioning paradigm, the ability of eight CD-1 mice to distinguish between 15 enantiomeric odor pairs was investigated. The results demonstrate a) that CD-1 mice are capable of discriminating between all odor pairs tested, b) that the enantiomeric odor pairs clearly differed in their degree of discriminability and thus in their perceptual similarity, and c) that pre-training with the rewarded stimuli led to improved initial but not terminal or overall performance. A comparison between the proportion of discriminated enantiomeric odor pairs of the CD-1 mice and those of other species tested in earlier studies on the same discrimination tasks (or on subsets thereof) shows a significant positive correlation between discrimination performance and the number of functional olfactory receptor genes. These findings provide the first evidence of a highly developed ability of CD-1 mice to discriminate between an array of non-pheromonal chiral odorants. Further, they suggest that a species' olfactory discrimination capabilities for these odorants may be correlated with its number of functional olfactory receptor genes. The data presented here may provide useful information for the interpretation of findings from electrophysiological or imaging studies in the mouse and the elucidation of odor structure-activity relationships.

Olfactory discrimination ability of CD-1 mice for a large array of enantiomers

PubMed Central

Laska, Matthias; Shepherd, Gordon M.

2006-01-01

With use of a conditioning paradigm, the ability of eight CD-1 mice to distinguish between 15 enantiomeric odor pairs was investigated. The results demonstrate a) that CD-1 mice are capable of discriminating between all odor pairs tested, b) that the enantiomeric odor pairs clearly differed in their degree of discriminability and thus in their perceptual similarity, and c) that pre-training with the rewarded stimuli led to improved initial but not terminal or overall performance. A comparison between the proportion of discriminated enantiomeric odor pairs of the CD-1 mice and those of other species tested in earlier studies on the same discrimination tasks (or on subsets thereof) shows a significant positive correlation between discrimination performance and the number of functional olfactory receptor genes. These findings provide the first evidence of a highly developed ability of CD-1 mice to discriminate between an array of non-pheromonal chiral odorants. Further, they suggest that a species′ olfactory discrimination capabilities for these odorants may be correlated with its number of functional olfactory receptor genes. The data presented here may provide useful information for the interpretation of findings from electrophysiological or imaging studies in the mouse and the elucidation of odor structure-activity relationships. PMID:17045753

Human red blood cell recognition enhancement with three-dimensional morphological features obtained by digital holographic imaging

NASA Astrophysics Data System (ADS)

Jaferzadeh, Keyvan; Moon, Inkyu

2016-12-01

The classification of erythrocytes plays an important role in the field of hematological diagnosis, specifically blood disorders. Since the biconcave shape of red blood cell (RBC) is altered during the different stages of hematological disorders, we believe that the three-dimensional (3-D) morphological features of erythrocyte provide better classification results than conventional two-dimensional (2-D) features. Therefore, we introduce a set of 3-D features related to the morphological and chemical properties of RBC profile and try to evaluate the discrimination power of these features against 2-D features with a neural network classifier. The 3-D features include erythrocyte surface area, volume, average cell thickness, sphericity index, sphericity coefficient and functionality factor, MCH and MCHSD, and two newly introduced features extracted from the ring section of RBC at the single-cell level. In contrast, the 2-D features are RBC projected surface area, perimeter, radius, elongation, and projected surface area to perimeter ratio. All features are obtained from images visualized by off-axis digital holographic microscopy with a numerical reconstruction algorithm, and four categories of biconcave (doughnut shape), flat-disc, stomatocyte, and echinospherocyte RBCs are interested. Our experimental results demonstrate that the 3-D features can be more useful in RBC classification than the 2-D features. Finally, we choose the best feature set of the 2-D and 3-D features by sequential forward feature selection technique, which yields better discrimination results. We believe that the final feature set evaluated with a neural network classification strategy can improve the RBC classification accuracy.

Analysis of the discriminative methods for diagnosis of benign and malignant solitary pulmonary nodules based on serum markers.

PubMed

Wang, Wanping; Liu, Mingyue; Wang, Jing; Tian, Rui; Dong, Junqiang; Liu, Qi; Zhao, Xianping; Wang, Yuanfang

2014-01-01

Screening indexes of tumor serum markers for benign and malignant solitary pulmonary nodules (SPNs) were analyzed to find the optimum method for diagnosis. Enzyme-linked immunosorbent assays, an automatic immune analyzer and radioimmunoassay methods were used to examine the levels of 8 serum markers in 164 SPN patients, and the sensitivity for differential diagnosis of malignant or benign SPN was compared for detection using a single plasma marker or a combination of markers. The results for serological indicators that closely relate to benign and malignant SPNs were screened using the Fisher discriminant analysis and a non-conditional logistic regression analysis method, respectively. The results were then verified by the k-means clustering analysis method. The sensitivity when using a combination of serum markers to detect SPN was higher than that using a single marker. By Fisher discriminant analysis, cytokeratin 19 fragments (CYFRA21-1), carbohydrate antigen 125 (CA125), squamous cell carcinoma antigen (SCC) and breast cancer antigen (CA153), which relate to the benign and malignant SPNs, were screened. Through non-conditional logistic regression analysis, CYFRA21-1, SCC and CA153 were obtained. Using the k-means clustering analysis, the cophenetic correlation coefficient (0.940) obtained by the Fisher discriminant analysis was higher than that obtained with logistic regression analysis (0.875). This study indicated that the Fisher discriminant analysis functioned better in screening out serum markers to recognize the benign and malignant SPN. The combined detection of CYFRA21-1, CA125, SCC and CA153 is an effective way to distinguish benign and malignant SPN, and will find an important clinical application in the early diagnosis of SPN. © 2014 S. Karger GmbH, Freiburg.

Evaluation of a pilot workload metric for simulated VTOL landing tasks

NASA Technical Reports Server (NTRS)

North, R. A.; Graffunder, K.

1979-01-01

A methodological approach to measuring workload was investigated for evaluation of new concepts in VTOL aircraft displays. Multivariate discriminant functions were formed from conventional flight performance and/or visual response variables to maximize detection of experimental differences. The flight performance variable discriminant showed maximum differentiation between crosswind conditions. The visual response measure discriminant maximized differences between fixed vs. motion base conditions and experimental displays. Physiological variables were used to attempt to predict the discriminant function values for each subject/condition/trial. The weights of the physiological variables in these equations showed agreement with previous studies. High muscle tension, light but irregular breathing patterns, and higher heart rate with low amplitude all produced higher scores on this scale and thus, represented higher workload levels.

Clinical Use of an Optical Coherence Tomography Linear Discriminant Function for Differentiating Glaucoma From Normal Eyes.

PubMed

Choi, Yun Jeong; Jeoung, Jin Wook; Park, Ki Ho; Kim, Dong Myung

2016-03-01

To determine and validate the diagnostic ability of a linear discriminant function (LDF) based on retinal nerve fiber layer (RNFL) and ganglion cell-inner plexiform layer (GCIPL) thickness obtained using high-definition optical coherence tomography (Cirrus HD-OCT) for discriminating between healthy controls and early glaucoma subjects. We prospectively selected 214 healthy controls and 152 glaucoma subjects (teaching set) and another independent sample of 86 healthy controls and 71 glaucoma subjects (validating set). Two scans, including 1 macular and 1 peripapillary RNFL scan, were obtained. After calculating the LDF in the teaching set using the binary logistic regression analysis, receiver operating characteristic curves were plotted and compared between the OCT-provided parameters and LDF in the validating set. The proposed LDF was 16.529-(0.132×superior RNFL)-(0.064×inferior RNFL)+(0.039×12 o'clock RNFL)+(0.038×1 o'clock RNFL)+(0.084×superior GCIPL)-(0.144×minimum GCIPL). The highest area under the receiver operating characteristic (AUROC) curve was obtained for LDF in both sets (AUROC=0.95 and 0.96). In the validating set, the LDF showed significantly higher AUROC than the best RNFL (inferior RNFL=0.91) and GCIPL parameter (minimum GCIPL=0.88). The LDF yielded a sensitivity of 93.0% at a fixed specificity of 85.0%. The LDF showed better diagnostic ability for differentiating between healthy and early glaucoma subjects than individual OCT parameters. A classification algorithm based on the LDF can be used in the OCT analysis for glaucoma diagnosis.

Sex and race determination of crania by calipers and computer : a test of the Giles and Elliot discriminant functions in 52 forensic cases.

DOT National Transportation Integrated Search

1979-01-01

The Giles and Elliot discriminant functions diagnosing sex and race from cranial measurements were tested on a series of forensically examined crania of known sex and race. Of 52 crania of known sex, 46 (88%) were correctly diagnosed. Racial diagnose...

Optical Implementation Of The Synthetic Discrimination Function

NASA Astrophysics Data System (ADS)

Butler, Steve; Riggins, James

1985-01-01

Computer-generated holograms of geometrical shape and synthetic discriminant function (SDF) matched filters are modeled and produced. The models include ideal correlations and Allebach-Keegan binary holograms. A distinction between Phase-Only-Information and Phase-Only-Material Filters is demonstrated. Signal-to-noise and efficiency measurements were made on the resultant correlation planes.

A new method for fingerprinting sediments source contributions using distances from discriminant function analysis

USDA-ARS?s Scientific Manuscript database

Mixing models have been used to predict sediment source contributions. The inherent problem of the mixing models limited the number of sediment sources. The objective of this study is to develop and evaluate a new method using Discriminant Function Analysis (DFA) to fingerprint sediment source contr...

Gender identification of Caspian Terns using external morphology and discriminant function analysis

USGS Publications Warehouse

Ackerman, Joshua T.; Takekawa, John Y.; Bluso, J.D.; Yee, J.L.; Eagles-Smith, Collin A.

2008-01-01

Caspian Tern (Sterna caspia) plumage characteristics are sexually monochromatic and gender cannot easily be distinguished in the field without extensive behavioral observations. We assessed sexual size dimorphism and developed a discriminant function to assign gender in Caspian Terns based on external morphology. We collected and measured Caspian Terns in San Francisco Bay, California, and confirmed their gender based on necropsy and genetic analysis. Of the eight morphological measurements we examined, only bill depth at the gonys and head plus bill length differed between males and females with males being larger than females. A discriminant function using both bill depth at the gonys and head plus bill length accurately assigned gender of 83% of terns for which gender was known. We improved the accuracy of our discriminant function to 90% by excluding individuals that had less than a 75% posterior probability of correctly being assigned to gender. Caspian Terns showed little sexual size dimorphism in many morphometries, but our results indicate they can be reliably assigned to gender in the field using two morphological measurements.

Immunological discrimination of Atlantic striped bass stocks

USGS Publications Warehouse

Schill, W.B.; Dorazio, R.M.

1990-01-01

Stocks of Atlantic striped bass Morone saxatilis that were assumed to be geographically isolated during spawning showed strong antigenic differences in blood serum albumin. A discriminant function was estimated from the immunologic responses of northern (Canadian and Hudson River) and southern (Chesapeake Bay and Roanoke River) stocks to two reference antisera. The function correctly classified 92% of the northern and 95% of the southern fish in the training set. Cross-validation revealed similar percentages of correct classification for fish that were of known origin but not used to estimate the discriminant function. Monte Carlo experiments were used to evaluate the ability of the discriminant function to predict the relative contribution of northern fish in samples of various size and stock composition. Averages of predicted proportions of northern fish in the samples agreed well with actual proportions. Coefficients of variation (100 × SD/mean) in the predicted proportions ranged from 1.5 to 36% for samples of 50–400 fish that contained at least 10% northern stock. In samples that contained only 2% northern stock, however, at least 1,600 fish were required to achieve similar levels of precision.

Managing uncertainty: a grounded theory of stigma in transgender health care encounters.

PubMed

Poteat, Tonia; German, Danielle; Kerrigan, Deanna

2013-05-01

A growing body of literature supports stigma and discrimination as fundamental causes of health disparities. Stigma and discrimination experienced by transgender people have been associated with increased risk for depression, suicide, and HIV. Transgender stigma and discrimination experienced in health care influence transgender people's health care access and utilization. Thus, understanding how stigma and discrimination manifest and function in health care encounters is critical to addressing health disparities for transgender people. A qualitative, grounded theory approach was taken to this study of stigma in health care interactions. Between January and July 2011, fifty-five transgender people and twelve medical providers participated in one-time in-depth interviews about stigma, discrimination, and health care interactions between providers and transgender patients. Due to the social and institutional stigma against transgender people, their care is excluded from medical training. Therefore, providers approach medical encounters with transgender patients with ambivalence and uncertainty. Transgender people anticipate that providers will not know how to meet their needs. This uncertainty and ambivalence in the medical encounter upsets the normal balance of power in provider-patient relationships. Interpersonal stigma functions to reinforce the power and authority of the medical provider during these interactions. Functional theories of stigma posit that we hold stigmatizing attitudes because they serve specific psychological functions. However, these theories ignore how hierarchies of power in social relationships serve to maintain and reinforce inequalities. The findings of this study suggest that interpersonal stigma also functions to reinforce medical power and authority in the face of provider uncertainty. Within functional theories of stigma, it is important to acknowledge the role of power and to understand how stigmatizing attitudes function to maintain systems of inequality that contribute to health disparities. Published by Elsevier Ltd.

Sexuality-related work discrimination and its association with the health of sexual minority emerging and young adult men in the Detroit Metro Area

PubMed Central

Bauermeister, José A.; Meanley, Steven; Hickok, Andrew; Pingel, Emily; VanHemert, William; Loveluck, Jimena

2013-01-01

Discrimination has been linked to negative health outcomes among minority populations. The increasing evidence regarding health disparities among sexual minorities has underscored the importance of addressing sexuality discrimination as a public health issue. We conducted a web-based survey between May and September of 2012 in order to obtain a diverse sample of young men who have sex with men (ages 18–29; N = 397; 83% gay; 49% Black, 27% White, 15% Latino) living in the Detroit Metro Area (Michigan, USA). Using multivariate regression models, we examined the association between overall health (self-rated health, days in prior month when their physical or mental health was not good, limited functionality) and experiences of sexuality-based work discrimination. Fifteen percent reported at least one experience of sexuality-based work discrimination in the prior year. Recent workplace discrimination was associated with poorer self-rated health, a greater number of days when health was not good, and more functional limitation. We discuss the importance of addressing sexuality-related discrimination as a public health problem and propose multilevel intervention strategies to address these discriminatory practices. PMID:24659928

Giant pandas use odor cues to discriminate kin from nonkin.

PubMed

Gilad, Oranit; Swaisgood, Ronald R; Owen, Megan A; Zhou, Xiaoping

2016-08-01

Sociality is an important factor in both the mechanism and function of kin recognition, yet it is little explored in solitary species. While there may be future opportunities for nepotistic functions of kin discrimination among solitary species, the ability to discriminate kin from nonkin may still have important roles in social regulation. The solitary giant panda Ailuropoda melanoleuca offers a good model system to explore kin discrimination in a solitary mammal. As kin discrimination in many other mammals is olfactorily mediated, we investigated whether giant pandas are able to discriminate odor cues from daughters even after months and years of separation. Our results indicate that giant pandas are capable of discriminating between kin and nonkin using odor cues available in urine and body odor. Daughters preferentially investigated the odors of unrelated adult female pandas over the odors of their mothers, and mothers spent more time investigating the odors of unrelated age-matched female pandas over those from their daughters. Because these studies were conducted months or years after the mother-daughter period of dependency ended, it is still unclear what mechanism is used for recognition. Long-term olfactory memories and phenotype matching should both be considered, and further studies are required for such determination.

Sexuality-related work discrimination and its association with the health of sexual minority emerging and young adult men in the Detroit Metro Area.

PubMed

Bauermeister, José A; Meanley, Steven; Hickok, Andrew; Pingel, Emily; Vanhemert, William; Loveluck, Jimena

2014-03-01

Discrimination has been linked to negative health outcomes among minority populations. The increasing evidence regarding health disparities among sexual minorities has underscored the importance of addressing sexuality discrimination as a public health issue. We conducted a web-based survey between May and September of 2012 in order to obtain a diverse sample of young men who have sex with men (ages 18-29; N = 397; 83% gay; 49% Black, 27% White, 15% Latino) living in the Detroit Metro Area (Michigan, USA). Using multivariate regression models, we examined the association between overall health (self-rated health, days in prior month when their physical or mental health was not good, limited functionality) and experiences of sexuality-based work discrimination. Fifteen percent reported at least one experience of sexuality-based work discrimination in the prior year. Recent workplace discrimination was associated with poorer self-rated health, a greater number of days when health was not good, and more functional limitation. We discuss the importance of addressing sexuality-related discrimination as a public health problem and propose multilevel intervention strategies to address these discriminatory practices.

Superiority of a functional leukocyte adhesiveness/aggregation test over the white blood cell count to discriminate between mild and significant inflammatory response in patients with acute bacterial infections.

PubMed

Rogowski, Ori; Rotstein, Rivka; Zeltzer, David; Misgav, Sarit; Justo, Daniel; Avitzour, Daniel; Mardi, Tamar; Serov, Jacob; Arber, Nadir; Berliner, Shlomo; Shapira, Itzhak

2002-01-01

Electronic cell counters may underestimate the white blood cell count (WBCC) in the presence of aggregated leukocytes. In the present study we focused on the possibility of using a functional, as opposed to an anatomic, count to circumvent this eventual underestimation. A model of bacterial infection was used because of the importance of leukocytosis in the physician's clinical decision-making process. There were 35 patients with low C-reactive protein (CRP) concentrations (0.5-4.9 mg/dL), 45 with intermediate (5-9.9 mg/dL), and 120 with relatively high (>10 mg/dL) CRP concentrations. A significant (P=0.008) difference was noted between the state of leukocyte adhesiveness/aggregation in the peripheral blood of individuals with low CRP concentrations (3.5%+/-4.3%) and those with high CRP concentrations (7.4%+/-8%), while there was no significant difference in the respective number of WBCs per cubic millimeter (cmm) (11,600 +/- 5,500 and 14,000 +/- 7,200, respectively). We raise the possibility that a functional test might be superior over an anatomic count in patients with acute bacterial infection and a significant acute phase response. Copyright 2002 Wiley-Liss, Inc.

A DCM study of spectral asymmetries in feedforward and feedback connections between visual areas V1 and V4 in the monkey.

PubMed

Bastos, A M; Litvak, V; Moran, R; Bosman, C A; Fries, P; Friston, K J

2015-03-01

This paper reports a dynamic causal modeling study of electrocorticographic (ECoG) data that addresses functional asymmetries between forward and backward connections in the visual cortical hierarchy. Specifically, we ask whether forward connections employ gamma-band frequencies, while backward connections preferentially use lower (beta-band) frequencies. We addressed this question by modeling empirical cross spectra using a neural mass model equipped with superficial and deep pyramidal cell populations-that model the source of forward and backward connections, respectively. This enabled us to reconstruct the transfer functions and associated spectra of specific subpopulations within cortical sources. We first established that Bayesian model comparison was able to discriminate between forward and backward connections, defined in terms of their cells of origin. We then confirmed that model selection was able to identify extrastriate (V4) sources as being hierarchically higher than early visual (V1) sources. Finally, an examination of the auto spectra and transfer functions associated with superficial and deep pyramidal cells confirmed that forward connections employed predominantly higher (gamma) frequencies, while backward connections were mediated by lower (alpha/beta) frequencies. We discuss these findings in relation to current views about alpha, beta, and gamma oscillations and predictive coding in the brain. Copyright © 2015. Published by Elsevier Inc.

Towards a needle-free diagnosis of malaria: in vivo identification and classification of red and white blood cells containing haemozoin.

PubMed

Burnett, Jennifer L; Carns, Jennifer L; Richards-Kortum, Rebecca

2017-11-07

Optical detection of circulating haemozoin has been suggested as a needle free method to diagnose malaria using in vivo microscopy. Haemozoin is generated within infected red blood cells by the malaria parasite, serving as a highly specific, endogenous biomarker of malaria. However, phagocytosis of haemozoin by white blood cells which persist after the infection is resolved presents the potential for false positive diagnosis; therefore, the focus of this work is to identify a feature of the haemozoin signal to discriminate between infected red blood cells and haemozoin-containing white blood cells. Conventional brightfield microscopy of thin film blood smears was used to analyse haemozoin absorbance signal in vitro. Cell type and parasite maturity were morphologically determined using colocalized DAPI staining. The ability of features to discriminate between infected red blood cells and haemozoin-containing white blood cells was evaluated using images of smears from subjects infected with two species of Plasmodium, Plasmodium yoelii and Plasmodium falciparum. Discriminating features identified by blood smear microscopy were characterized in vivo in P. yoelii-infected mice. Two features of the haemozoin signal, haemozoin diameter and normalized intensity difference, were identified as potential parameters to differentiate infected red blood cells and haemozoin-containing white blood cells. Classification performance was evaluated using the area under the receiver operating characteristic curve, with area under the curve values of 0.89 for the diameter parameter and 0.85 for the intensity parameter when assessed in P. yoelii samples. Similar results were obtained from P. falciparum blood smears, showing an AUC of 0.93 or greater for both classification features. For in vivo investigations, the intensity-based metric was the best classifier, with an AUC of 0.91. This work demonstrates that size and intensity features of haemozoin absorbance signal collected by in vivo microscopy are effective classification metrics to discriminate infected red blood cells from haemozoin-containing white blood cells. This reduces the potential for false positive results associated with optical imaging strategies for in vivo diagnosis of malaria based on the endogenous biomarker haemozoin.

Near-field photothermal microspectroscopy for adult stem-cell identification and characterization.

PubMed

Grude, Olaug; Hammiche, Azzedine; Pollock, Hubert; Bentley, Adam J; Walsh, Michael J; Martin, Francis L; Fullwood, Nigel J

2007-12-01

The identification of stem cells in adult tissue is a challenging problem in biomedicine. Currently, stem cells are identified by individual epitopes, which are generally tissue specific. The discovery of a stem-cell marker common to other adult tissue types could open avenues in the development of therapeutic stem-cell strategies. We report the use of the novel technique of Fourier transform infrared near-field photothermal microspectroscopy (FTIR-PTMS) for the characterization of stem cells, transit amplifying (TA) cells and terminally differentiated (TD) cells in the corneal epithelium. Principal component analysis (PCA) data demonstrate excellent discrimination of cell type by spectra. PCA in combination with linear discriminant analysis (PCA-LDA) shows that FTIR-PTMS very effectively discriminates between the three cell populations. Statistically significant differences above the 99% confidence level between IR spectra from stem cells and TA cells suggest that nucleic acid conformational changes are an important component of the differences between spectral data from the two cell types. FTIR-PTMS is a new addition to existing spectroscopy methods based on the concept of interfacing a conventional FTIR spectrometer with an atomic force microscope equipped with a near-field thermal sensing probe. FTIR-PTMS spectroscopy currently has spatial resolution that is similar to that of diffraction-limited optical detection FTIR spectroscopy techniques, but as a near-field probing technique has considerable potential for further improvement. Our work also suggests that FTIR-PTMS is potentially more sensitive than synchrotron radiation FTIR spectroscopy for some applications. Microspectroscopy techniques like FTIR-PTMS provide information about the entire molecular composition of cells, in contrast to epitope recognition that only considers the presence or absence of individual molecules. Our results with FTIR-PTMS on corneal stem cells are promising for the potential development of an IR spectral fingerprint for stem cells.

Odor-Induced Neuronal Rhythms in the Olfactory Bulb Are Profoundly Modified in ob/ob Obese Mice

PubMed Central

Chelminski, Yan; Magnan, Christophe; Luquet, Serge H.; Everard, Amandine; Meunier, Nicolas; Gurden, Hirac; Martin, Claire

2017-01-01

Leptin, the product of the Ob(Lep) gene, is a peptide hormone that plays a major role in maintaining the balance between food intake and energy expenditure. In the brain, leptin receptors are expressed by hypothalamic cells but also in the olfactory bulb, the first central structure coding for odors, suggesting a precise function of this hormone in odor-evoked activities. Although olfaction plays a key role in feeding behavior, the ability of the olfactory bulb to integrate the energy-related signal leptin is still missing. Therefore, we studied the fate of odor-induced activity in the olfactory bulb in the genetic context of leptin deficiency using the obese ob/ob mice. By means of an odor discrimination task with concomitant local field potential recordings, we showed that ob/ob mice perform better than wild-type (WT) mice in the early stage of the task. This behavioral gain of function was associated in parallel with profound changes in neuronal oscillations in the olfactory bulb. The distribution of the peaks in the gamma frequency range was shifted toward higher frequencies in ob/ob mice compared to WT mice before learning. More notably, beta oscillatory activity, which has been shown previously to be correlated with olfactory discrimination learning, was longer and stronger in expert ob/ob mice after learning. Since oscillations in the olfactory bulb emerge from mitral to granule cell interactions, our results suggest that cellular dynamics in the olfactory bulb are deeply modified in ob/ob mice in the context of olfactory learning. PMID:28154537

[Pancreatic acinar neoplasms : Comparative molecular characterization].

PubMed

Bergmann, F

2016-11-01

Pancreatic acinar cell carcinomas are biologically aggressive neoplasms for which treatment options are very limited. The molecular mechanisms of tumor initiation and progression are largely not understood and precursor lesions have not yet been identified. In this study, pancreatic acinar cell carcinomas were cytogenetically characterized as well as by molecular and immunohistochemical analyses. Corresponding investigations were carried out on pancreatic ductal adenocarcinomas and pancreatic neuroendocrine neoplasms augmented by functional analyses. We show that pancreatic acinar cell carcinomas display a microsatellite stable, chromosomal unstable genotype, characterized by recurrent chromosomal imbalances that clearly discriminate them from pancreatic ductal adenocarcinomas and neuroendocrine neoplasms. Based on findings obtained from comparative genomic hybridization, candidate genes could be identified, such as deleted in colorectal cancer (DCC) and c-MYC. Furthermore, several therapeutic targets were identified in acinar cell carcinomas and other pancreatic neoplasms, including epidermal growth factor receptor (EGFR), L1 cell adhesion molecule (L1CAM) and heat shock protein 90 (HSP90). Moreover, L1CAM was shown to play a significant role in the tumorigenesis of pancreatic ductal adenocarcinoma. Functional analyses in cell lines derived from pancreatic neuroendocrine neoplasms revealed promising anti-tumorigenic effects using EGFR and HSP90 inhibitors affecting the cell cycle and in the case of HSP90, regulating several other oncogenes. Finally, based on mutational analyses of mitochondrial DNA, molecular evidence is provided that acinar cell cystadenomas (or better cystic acinar transformation) represent non-clonal lesions, suggesting an inflammatory reactive non-neoplastic nature.

The discriminative stimulus effects of a nicotine-ethanol compound in rats: Extinction with the parts differs from the whole.

PubMed

Troisi, Joseph R; Dooley, Thomas F; Craig, Elizabeth M

2013-12-01

Nicotine and ethyl alcohol (EtOH) interact neurophysiologically and induce internal sensory states that contribute to their coabuse. Evaluating the combined internal sensory effects of nicotine and alcohol may be important for understanding this nexus. With rats, this investigation used an operant drug discrimination procedure to establish discriminative stimulus control with a mixture of nicotine plus EtOH (NE) at doses of nicotine (0.3 mg/kg) and EtOH (1.0 g/kg) that have previously been shown to be equally salient (Gauvin & Holloway, 1993). In Experiment (Exp) 1 the NE compound mixture continued to evoke responding despite extinction of responding with nicotine and EtOH alone. In Exp 2 the NE mixture was reliably discriminated from the nicotine and EtOH elements. Experiment 3 showed that the discriminative functions of the NE mixture emerged when the nicotine and EtOH elements were combined following their initial establishment as separate discriminative stimuli; however, nicotine evoked more control than EtOH. Extinction of responding with the NE mixture impacted rates of responding with nicotine and EtOH alone. The results of the all three studies parallel findings with exteroceptive Pavlovian literature in showing that extinction of responding with the elemental parts does not appear to impact the whole-but, extinction with the whole appears to affect its parts. The multielement discriminative function of a NE mixture appears to be a "unique cue" that differs qualitatively from nicotine or EtOH alone. Associative factors related to compound conditioning (i.e., configural learning) play an important role in mediating the discriminative functions of drug mixtures.

Cell Chauvinism

ERIC Educational Resources Information Center

Keller, Dolores Elaine

1972-01-01

Indicates that biological terminology, such as mother cell'' and labels of sex factors in bacteria, reflect discrimination against females by reinforcing perpetuation of stereotyped gender roles. (AL)

Functional reprogramming of polyploidization in megakaryocytes.

PubMed

Trakala, Marianna; Rodríguez-Acebes, Sara; Maroto, María; Symonds, Catherine E; Santamaría, David; Ortega, Sagrario; Barbacid, Mariano; Méndez, Juan; Malumbres, Marcos

2015-01-26

Polyploidization is a natural process that frequently accompanies differentiation; its deregulation is linked to genomic instability and cancer. Despite its relevance, why cells select different polyploidization mechanisms is unknown. Here we report a systematic genetic analysis of endomitosis, a process in which megakaryocytes become polyploid by entering mitosis but aborting anaphase. Whereas ablation of the APC/C cofactor Cdc20 results in mitotic arrest and severe thrombocytopenia, lack of the kinases Aurora-B, Cdk1, or Cdk2 does not affect megakaryocyte polyploidization or platelet levels. Ablation of Cdk1 forces a switch to endocycles without mitosis, whereas polyploidization in the absence of Cdk1 and Cdk2 occurs in the presence of aberrant re-replication events. Importantly, ablation of these kinases rescues the defects in Cdc20 null megakaryocytes. These findings suggest that endomitosis can be functionally replaced by alternative polyploidization mechanisms in vivo and provide the cellular basis for therapeutic approaches aimed to discriminate mitotic and polyploid cells. Copyright © 2015 Elsevier Inc. All rights reserved.

Proteomic Analysis of the Mediator Complex Interactome in Saccharomyces cerevisiae.

PubMed

Uthe, Henriette; Vanselow, Jens T; Schlosser, Andreas

2017-02-27

Here we present the most comprehensive analysis of the yeast Mediator complex interactome to date. Particularly gentle cell lysis and co-immunopurification conditions allowed us to preserve even transient protein-protein interactions and to comprehensively probe the molecular environment of the Mediator complex in the cell. Metabolic 15 N-labeling thereby enabled stringent discrimination between bona fide interaction partners and nonspecifically captured proteins. Our data indicates a functional role for Mediator beyond transcription initiation. We identified a large number of Mediator-interacting proteins and protein complexes, such as RNA polymerase II, general transcription factors, a large number of transcriptional activators, the SAGA complex, chromatin remodeling complexes, histone chaperones, highly acetylated histones, as well as proteins playing a role in co-transcriptional processes, such as splicing, mRNA decapping and mRNA decay. Moreover, our data provides clear evidence, that the Mediator complex interacts not only with RNA polymerase II, but also with RNA polymerases I and III, and indicates a functional role of the Mediator complex in rRNA processing and ribosome biogenesis.

Assessment of craniometric traits in South Indian dry skulls for sex determination.

PubMed

Ramamoorthy, Balakrishnan; Pai, Mangala M; Prabhu, Latha V; Muralimanju, B V; Rai, Rajalakshmi

2016-01-01

The skeleton plays an important role in sex determination in forensic anthropology. The skull bone is considered as the second best after the pelvic bone in sex determination due to its better retention of morphological features. Different populations have varying skeletal characteristics, making population specific analysis for sex determination essential. Hence the objective of this investigation is to obtain the accuracy of sex determination using cranial parameters of adult skulls to the highest percentage in South Indian population and to provide a baseline data for sex determination in South India. Seventy adult preserved human skulls were taken and based on the morphological traits were classified into 43 male skulls and 27 female skulls. A total of 26 craniometric parameters were studied. The data were analyzed by using the SPSS discriminant function. The analysis of stepwise, multivariate, and univariate discriminant function gave an accuracy of 77.1%, 85.7%, and 72.9% respectively. Multivariate direct discriminant function analysis classified skull bones into male and female with highest levels of accuracy. Using stepwise discriminant function analysis, the most dimorphic variable to determine sex of the skull, was biauricular breadth followed by weight. Subjecting the best dimorphic variables to univariate discriminant analysis, high levels of accuracy of sexual dimorphism was obtained. Percentage classification of high accuracies were obtained in this study indicating high level of sexual dimorphism in the crania, setting specific discriminant equations for the gender determination in South Indian people. Copyright © 2015 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.

Expression profiling and functional analysis of Toll-like receptors in primary healthy human nasal epithelial cells shows no correlation and a refractory LPS response.

PubMed

van Tongeren, J; Röschmann, K I L; Reinartz, S M; Luiten, S; Fokkens, W J; de Jong, E C; van Drunen, C M

2015-01-01

Innate immune recognition via Toll-like receptors (TLRs) on barrier cells like epithelial cells has been shown to influence the regulation of local immune responses. Here we determine expression level variations and functionality of TLRs in nasal epithelial cells from healthy donors. Expression levels of the different TLRs on primary nasal epithelial cells from healthy donors derived from inferior turbinates was determined by RT-PCR. Functionality of the TLRs was determined by stimulation with the respective ligand and evaluation of released mediators by Luminex ELISA. Primary nasal epithelial cells express different levels of TLR1-6 and TLR9. We were unable to detect mRNA of TLR7, TLR8 and TLR10. Stimulation with Poly(I:C) resulted in a significant increased secretion of IL-4, IL-6, RANTES, IP-10, MIP-1β, VEGF, FGF, IL-1RA, IL-2R and G-CSF. Stimulation with PGN only resulted in significant increased production of IL-6, VEGF and IL-1RA. Although the expression of TLR4 and co-stimulatory molecules could be confirmed, primary nasal epithelial cells appeared to be unresponsive to stimulation with LPS. Furthermore, we observed huge individual differences in TLR agonist-induced mediator release, which did not correlate with the respective expression of TLRs. Our data suggest that nasal epithelium seems to have developed a delicate system of discrimination and recognition of microbial patterns. Hypo-responsiveness to LPS could provide a mechanism to dampen the inflammatory response in the nasal mucosa in order to avoid a chronic inflammatory response. Individual, differential expression of TLRs on epithelial cells and functionality in terms of released mediators might be a crucial factor in explaining why some people develop allergies to common inhaled antigens, and others do not.

Electrophoretic cell separation using microspheres. [purification of lymphocytes

NASA Technical Reports Server (NTRS)

Smolka, A.; Sachs, G.

1980-01-01

Methods of cell separation based on the electrokinetic properties of the cell membrane offer a degree of discrimination among cell populations which is not available with methods based on cell size or density alone. Studies aimed at extending red cell separations using microspheres to purification of lymphocytes.

Noninvasive Detection and Imaging of Molecular Markers in Live Cardiomyocytes Derived from Human Embryonic Stem Cells

PubMed Central

Pascut, Flavius C.; Goh, Huey T.; Welch, Nathan; Buttery, Lee D.; Denning, Chris; Notingher, Ioan

2011-01-01

Raman microspectroscopy (RMS) was used to detect and image molecular markers specific to cardiomyocytes (CMs) derived from human embryonic stem cells (hESCs). This technique is noninvasive and thus can be used to discriminate individual live CMs within highly heterogeneous cell populations. Principal component analysis (PCA) of the Raman spectra was used to build a classification model for identification of individual CMs. Retrospective immunostaining imaging was used as the gold standard for phenotypic identification of each cell. We were able to discriminate CMs from other phenotypes with >97% specificity and >96% sensitivity, as calculated with the use of cross-validation algorithms (target 100% specificity). A comparison between Raman spectral images corresponding to selected Raman bands identified by the PCA model and immunostaining of the same cells allowed assignment of the Raman spectral markers. We conclude that glycogen is responsible for the discrimination of CMs, whereas myofibril proteins have a lesser contribution. This study demonstrates the potential of RMS for allowing the noninvasive phenotypic identification of hESC progeny. With further development, such label-free optical techniques may enable the separation of high-purity cell populations with mature phenotypes, and provide repeated measurements to monitor time-dependent molecular changes in live hESCs during differentiation in vitro. PMID:21190678

Identifying the molecular functions of electron transport proteins using radial basis function networks and biochemical properties.

PubMed

Le, Nguyen-Quoc-Khanh; Nguyen, Trinh-Trung-Duong; Ou, Yu-Yen

2017-05-01

The electron transport proteins have an important role in storing and transferring electrons in cellular respiration, which is the most proficient process through which cells gather energy from consumed food. According to the molecular functions, the electron transport chain components could be formed with five complexes with several different electron carriers and functions. Therefore, identifying the molecular functions in the electron transport chain is vital for helping biologists understand the electron transport chain process and energy production in cells. This work includes two phases for discriminating electron transport proteins from transport proteins and classifying categories of five complexes in electron transport proteins. In the first phase, the performances from PSSM with AAIndex feature set were successful in identifying electron transport proteins in transport proteins with achieved sensitivity of 73.2%, specificity of 94.1%, and accuracy of 91.3%, with MCC of 0.64 for independent data set. With the second phase, our method can approach a precise model for identifying of five complexes with different molecular functions in electron transport proteins. The PSSM with AAIndex properties in five complexes achieved MCC of 0.51, 0.47, 0.42, 0.74, and 1.00 for independent data set, respectively. We suggest that our study could be a power model for determining new proteins that belongs into which molecular function of electron transport proteins. Copyright © 2017 Elsevier Inc. All rights reserved.

Correlations between the Dielectric Properties and Exterior Morphology of Cells Revealed by Dielectrophoretic Field-Flow Fractionation

PubMed Central

Gascoyne, Peter R. C.; Shim, Sangjo; Noshari, Jamileh; Becker, Frederick F.; Stemke-Hale, Katherine

2013-01-01

Although dielectrophoresis (DEP) has great potential for addressing clinical cell isolation problems based on cell dielectric differences, a biological basis for predicting the DEP behavior of cells has been lacking. Here, the dielectric properties of the NCI-60 panel of tumor cell types have been measured by dielectrophoretic (DEP) field-flow fractionation, correlated with the exterior morphologies of the cells during growth, and compared with the dielectric and morphological characteristics of the subpopulations of peripheral blood. In agreement with earlier findings, cell total capacitance varied with both cell size and plasma membrane folding and the dielectric properties of the NCI-60 cell types in suspension reflected the plasma membrane area and volume of the cells at their growth sites. Therefore, the behavior of cells in DEP-based manipulations is largely determined by their exterior morphological characteristics prior to release into suspension. As a consequence, DEP is able to discriminate between cells of similar size having different morphological origins, offering a significant advantage over size-based filtering for isolating circulating tumor cells, for example. The findings provide a framework for anticipating cell dielectric behavior on the basis of structure-function relationships and suggest that DEP should be widely applicable as a surface marker-independent method for sorting cells. PMID:23172680

Multivariate geomorphic analysis of forest streams: Implications for assessment of land use impacts on channel condition

Treesearch

Richard. D. Wood-Smith; John M. Buffington

1996-01-01

Multivariate statistical analyses of geomorphic variables from 23 forest stream reaches in southeast Alaska result in successful discrimination between pristine streams and those disturbed by land management, specifically timber harvesting and associated road building. Results of discriminant function analysis indicate that a three-variable model discriminates 10...

Six-Month-Old Infants Use Analog Magnitudes to Represent Duration

ERIC Educational Resources Information Center

vanMarle, Kristy; Wynn, Karen

2006-01-01

While many studies have investigated duration discrimination in human adults and in nonhuman animals, few have investigated this ability in infants. Here, we report findings that 6-month-old infants are able to discriminate brief durations, and, as with other animal species, their discrimination function is characterized by Weber's Law:…

African American Male Adolescents' Hostile Responses to Perceived Racial Discrimination.

ERIC Educational Resources Information Center

Wakefield, William D.; Hudley, Cynthia

This study examined the hostile responses of adolescent African American males to acts of racial discrimination as a function of audience presence, noting attributions of personal control. Participants were 250 male African American students in grades 9-12 in an urban multiethnic high school who completed the Discrimination Response Index (DRI).…

Racial discrimination: a continuum of violence exposure for children of color.

PubMed

Sanders-Phillips, Kathy

2009-06-01

This article reviews and examines findings on the impact of racial discrimination on the development and functioning of children of color in the US. Based on current definitions of violence and child maltreatment, exposure to racial discrimination should be considered as a form of violence that can significantly impact child outcomes and limit the ability of parents and communities to provide support that promotes resiliency and optimal child development. In this article, a conceptual model of the effects of racial discrimination in children of color is presented. The model posits that exposure to racial discrimination may be a chronic source of trauma in the lives of many children of color that negatively influences mental and physical outcomes as well as parent and community support and functioning. Concurrent exposure to other forms of violence, including domestic, interpersonal and/or community violence, may exacerbate these effects. The impact of a potential continuum of violence exposure for children of color in the US and the need for future research and theoretical models on children's exposure to violence that attend to the impact of racial discrimination on child outcomes are discussed.

EphA2 is an epithelial cell pattern recognition receptor for fungal β-glucans

PubMed Central

Swidergall, Marc; Solis, Norma V.; Lionakis, Michail S.; Filler, Scott G.

2017-01-01

Oral epithelial cells discriminate between pathogenic and non-pathogenic stimuli, and only induce an inflammatory response when they are exposed to high levels of a potentially harmful microorganism. The pattern recognition receptors (PRRs) in epithelial cells that mediate this differential response are poorly understood. Here, we demonstrate that the ephrin type-A receptor 2 (EphA2) is an oral epithelial cell PRR that binds to exposed β-glucans on the surface of the fungal pathogen Candida albicans. Binding of C. albicans to EphA2 on oral epithelial cells activates signal transducer and activator of transcription 3 (Stat3) and mitogen-activated protein kinase signaling in an inoculum-dependent manner, and is required for induction of a pro-inflammatory and antifungal response. EphA2−/− mice have impaired inflammatory responses and reduced IL-17 signaling during oropharyngeal candidiasis, resulting in more severe disease. Our study reveals that EphA2 functions as PRR for β-glucans that senses epithelial cell fungal burden and is required for the maximal mucosal inflammatory response to C. albicans. PMID:29133884

Bacillus subtilis Protects Public Goods by Extending Kin Discrimination to Closely Related Species

PubMed Central

2017-01-01

ABSTRACT Kin discrimination systems are found in numerous communal contexts like multicellularity and are theorized to prevent exploitation of cooperative behaviors. The kin discrimination system in Bacillus subtilis differs from most other such systems because it excludes nonkin cells rather than including kin cells. Because nonkin are the target of the system, B. subtilis can potentially distinguish degrees of nonkin relatedness, not just kin versus nonkin. We examined this by testing a large strain collection of diverse Bacillus species against B. subtilis in different multicellular contexts. The effects of kin discrimination extend to nearby species, as the other subtilis clade species were treated with the same antagonism as nonkin. Species in the less-related pumilus clade started to display varied phenotypes but were mostly still discriminated against, while cereus clade members and beyond were no longer subject to kin discrimination. Seeking a reason why other species are perceived as antagonistic nonkin, we tested the ability of B. subtilis to steal communally produced surfactant from these species. We found that the species treated as nonkin were the only ones that made a surfactant that B. subtilis could utilize and that nonkin antagonism prevented such stealing when the two strains were mixed. The nonkin exclusion kin discrimination method thus allows effective protection of the cooperative behaviors prevalent in multicellularity while still permitting interactions with more distant species that are not a threat. PMID:28679746

Generation of high-yield insulin producing cells from human bone marrow mesenchymal stem cells.

PubMed

Jafarian, Arefeh; Taghikhani, Mohammad; Abroun, Saeid; Pourpak, Zahra; Allahverdi, Amir; Soleimani, Masoud

2014-07-01

Allogenic islet transplantation is a most efficient approach for treatment of diabetes mellitus. However, the scarcity of islets and long term need for an immunosuppressant limits its application. Recently, cell replacement therapies that generate of unlimited sources of β cells have been developed to overcome these limitations. In this study we have described a stage specific differentiation protocol for the generation of insulin producing islet-like clusters from human bone marrow mesenchymal stem cells (hBM-MSCs). This specific stepwise protocol induced differentiation of hMSCs into definitive endoderm, pancreatic endoderm and pancreatic endocrine cells that expressed of sox17, foxa2, pdx1, ngn3, nkx2.2, insulin, glucagon, somatostatin, pancreatic polypeptide, and glut2 transcripts respectively. In addition, immunocytochemical analysis confirmed protein expression of the above mentioned genes. Western blot analysis discriminated insulin from proinsulin in the final differentiated cells. In derived insulin producing cells (IPCs), secreted insulin and C-peptide was in a glucose dependent manner. We have developed a protocol that generates effective high-yield human IPCs from hBM-MSCs in vitro. These finding suggest that functional IPCs generated by this procedure can be used as a cell-based approach for insulin dependent diabetes mellitus.

Exploring Raman spectroscopy for the evaluation of glaucomatous retinal changes

NASA Astrophysics Data System (ADS)

Wang, Qi; Grozdanic, Sinisa D.; Harper, Matthew M.; Hamouche, Nicolas; Kecova, Helga; Lazic, Tatjana; Yu, Chenxu

2011-10-01

Glaucoma is a chronic neurodegenerative disease characterized by apoptosis of retinal ganglion cells and subsequent loss of visual function. Early detection of glaucoma is critical for the prevention of permanent structural damage and irreversible vision loss. Raman spectroscopy is a technique that provides rapid biochemical characterization of tissues in a nondestructive and noninvasive fashion. In this study, we explored the potential of using Raman spectroscopy for detection of glaucomatous changes in vitro. Raman spectroscopic imaging was conducted on retinal tissues of dogs with hereditary glaucoma and healthy control dogs. The Raman spectra were subjected to multivariate discriminant analysis with a support vector machine algorithm, and a classification model was developed to differentiate disease tissues versus healthy tissues. Spectroscopic analysis of 105 retinal ganglion cells (RGCs) from glaucomatous dogs and 267 RGCs from healthy dogs revealed spectroscopic markers that differentiated glaucomatous specimens from healthy controls. Furthermore, the multivariate discriminant model differentiated healthy samples and glaucomatous samples with good accuracy [healthy 89.5% and glaucomatous 97.6% for the same breed (Basset Hounds); and healthy 85.0% and glaucomatous 85.5% for different breeds (Beagles versus Basset Hounds)]. Raman spectroscopic screening can be used for in vitro detection of glaucomatous changes in retinal tissue with a high specificity.

Exploring Raman spectroscopy for the evaluation of glaucomatous retinal changes.

PubMed

Wang, Qi; Grozdanic, Sinisa D; Harper, Matthew M; Hamouche, Nicolas; Kecova, Helga; Lazic, Tatjana; Yu, Chenxu

2011-10-01

Glaucoma is a chronic neurodegenerative disease characterized by apoptosis of retinal ganglion cells and subsequent loss of visual function. Early detection of glaucoma is critical for the prevention of permanent structural damage and irreversible vision loss. Raman spectroscopy is a technique that provides rapid biochemical characterization of tissues in a nondestructive and noninvasive fashion. In this study, we explored the potential of using Raman spectroscopy for detection of glaucomatous changes in vitro. Raman spectroscopic imaging was conducted on retinal tissues of dogs with hereditary glaucoma and healthy control dogs. The Raman spectra were subjected to multivariate discriminant analysis with a support vector machine algorithm, and a classification model was developed to differentiate disease tissues versus healthy tissues. Spectroscopic analysis of 105 retinal ganglion cells (RGCs) from glaucomatous dogs and 267 RGCs from healthy dogs revealed spectroscopic markers that differentiated glaucomatous specimens from healthy controls. Furthermore, the multivariate discriminant model differentiated healthy samples and glaucomatous samples with good accuracy [healthy 89.5% and glaucomatous 97.6% for the same breed (Basset Hounds); and healthy 85.0% and glaucomatous 85.5% for different breeds (Beagles versus Basset Hounds)]. Raman spectroscopic screening can be used for in vitro detection of glaucomatous changes in retinal tissue with a high specificity.

Learning Discriminative Binary Codes for Large-scale Cross-modal Retrieval.

PubMed

Xu, Xing; Shen, Fumin; Yang, Yang; Shen, Heng Tao; Li, Xuelong

2017-05-01

Hashing based methods have attracted considerable attention for efficient cross-modal retrieval on large-scale multimedia data. The core problem of cross-modal hashing is how to learn compact binary codes that construct the underlying correlations between heterogeneous features from different modalities. A majority of recent approaches aim at learning hash functions to preserve the pairwise similarities defined by given class labels. However, these methods fail to explicitly explore the discriminative property of class labels during hash function learning. In addition, they usually discard the discrete constraints imposed on the to-be-learned binary codes, and compromise to solve a relaxed problem with quantization to obtain the approximate binary solution. Therefore, the binary codes generated by these methods are suboptimal and less discriminative to different classes. To overcome these drawbacks, we propose a novel cross-modal hashing method, termed discrete cross-modal hashing (DCH), which directly learns discriminative binary codes while retaining the discrete constraints. Specifically, DCH learns modality-specific hash functions for generating unified binary codes, and these binary codes are viewed as representative features for discriminative classification with class labels. An effective discrete optimization algorithm is developed for DCH to jointly learn the modality-specific hash function and the unified binary codes. Extensive experiments on three benchmark data sets highlight the superiority of DCH under various cross-modal scenarios and show its state-of-the-art performance.

The Utility of the MMPI-2 Malingering Discriminant Function Index in the Detection of Malingering: A Study of Criminal Defendants

ERIC Educational Resources Information Center

Toomey, Joseph A.; Kucharski, L. Thomas; Duncan, Scott

2009-01-01

This study examined the utility of the Minnesota Multiphasic Personality Inventory-2's (MMPI-2) malingering discriminant function index (M-DFI), recently developed by Bacchiochi and Bagby, in the detection of malingering in a forensic sample. Criminal defendants were divided into "malingering" and "not malingering" groups using…

Reduced Activation in Right Lateral Prefrontal Cortex and Anterior Cingulate Gyrus in Medication-Naive Adolescents with Attention Deficit Hyperactivity Disorder during Time Discrimination

ERIC Educational Resources Information Center

Smith, Anna B.; Taylor, Eric; Brammer, Michael; Halari, Rozmin; Rubia, Katya

2008-01-01

Background: Patients with attention deficit hyperactivity disorder (ADHD) under-perform when discriminating between durations differing by several hundred milliseconds. This function involves right prefrontal and anterior cingulate (AC) brain regions, which are structurally and functionally compromised in this patient group during executive tasks.…

Targeted Deletion of ERK5 MAP Kinase in the Developing Nervous System Impairs Development of GABAergic Interneurons in the Main Olfactory Bulb and Behavioral Discrimination between Structurally Similar Odorants

PubMed Central

Zou, Junhui; Pan, Yung-Wei; Wang, Zhenshan; Chang, Shih-Yu; Wang, Wenbin; Wang, Xin; Tournier, Cathy; Storm, Daniel R.; Xia, Zhengui

2012-01-01

ERK5 MAP kinase is highly expressed in the developing nervous system and has been implicated in promoting the survival of immature neurons in culture. However, its role in the development and function of the mammalian nervous system has not been established in vivo. Here, we report that conditional deletion of the erk5 gene in mouse neural stem cells during development reduces the number of GABAergic interneurons in the main olfactory bulb (OB). Our data suggest that this is due to a decrease in proliferation and an increase in apoptosis in the subventricular zone (SVZ) and rostral migratory stream (RMS) of ERK5 mutant mice. Interestingly, ERK5 mutant mice have smaller OB and are impaired in odor discrimination between structurally similar odorants. We conclude that ERK5 is a novel signaling pathway regulating developmental OB neurogenesis and olfactory behavior. PMID:22442076

Minimal functional β-cell mass in intraportal implants that reduces glycemic variability in type 1 diabetic recipients.

PubMed

Gillard, Pieter; Hilbrands, Robert; Van de Velde, Ursule; Ling, Zhidong; Lee, Da Hae; Weets, Ilse; Gorus, Frans; De Block, Christophe; Kaufman, Leonard; Mathieu, Chantal; Pipeleers, Daniel; Keymeulen, Bart

2013-11-01

Previous work has shown a correlation between β-cell number in cultured islet cell grafts and their ability to induce C-peptide secretion after intraportal implantation in C-peptide-negative type1 diabetic patients. In this cross-sectional study, we examined the minimal functional β-cell mass (FBM) in the implant that induces metabolic improvement. Glucose clamps assessed FBM in 42 recipients with established implants. C-peptide release during each phase was expressed as percentage of healthy control values. Its relative magnitude during a second hyperglycemic phase was most discriminative and therefore selected as a parameter to be correlated with metabolic effects. Recipients with functioning β-cell implants exhibited average FBM corresponding to 18% of that in normal control subjects (interquartile range 10-33%). Its relative magnitude negatively correlated with HbA1c levels (r = -0.47), daily insulin dose (r = -0.75), and coefficient of variation of fasting glycemia (CVfg) (r = -0.78, retained in multivariate analysis). A correlation between FBM and CVfg <25% appeared from the receiver operating characteristic curve (0.97 [95% CI 0.93-1.00]). All patients with FBM >37% exhibited CVfg <25% and a >50% reduction of their pretransplant CVfg; this occurred in none with FBM <5%. Implants with FBM >18% reduced CVfg from a median pretransplant value of 46 to <25%. Glucose clamping assesses the degree of restoration in FBM achieved by islet cell implants. Values >37% of normal control subjects appear needed to reduce glycemic variability in type 1 diabetic recipients. Further studies should examine whether the test can help guide decisions on additional islet cell transplants and on adjusting or stopping immunotherapy.

Discrimination of organic coffee via Fourier transform infrared-photoacoustic spectroscopy.

PubMed

Gordillo-Delgado, Fernando; Marín, Ernesto; Cortés-Hernández, Diego Mauricio; Mejía-Morales, Claudia; García-Salcedo, Angela Janet

2012-08-30

Procedures for the evaluation of the origin and quality of ground and roasted coffee are constantly needed for the associated industry due to complexity of the related market. Conventional Fourier transform infrared (FTIR) spectroscopy can be used for detecting changes in functional groups of compounds, such as coffee. However, dispersion, reflection and non-homogeneity of the sample matrix can cause problems resulting in low spectral quality. On the other hand, sample preparation frequently takes place in a destructive way. To overcome these difficulties, in this work a photoacoustic cell has been adapted as a detector in a FTIR spectrophotometer to perform a study of roasted and ground coffee from three varieties of Coffea arabica grown by organic and conventional methods. Comparison between spectra of coffee recorded by FTIR-photoacoustic spectrometry (PAS) and by FTIR spectrophotometry showed a better resolution of the former method, which, aided by principal components analysis, allowed the identification of some absorption bands that allow the discrimination between organic and conventional coffee. The results obtained provide information about the spectral behavior of coffee powder which can be useful for establishing discrimination criteria. It has been demonstrated that FTIR-PAS can be a useful experimental tool for the characterization of coffee. Copyright © 2012 Society of Chemical Industry.

The Activation and Inactivation of Mature CD4 T cells: A Case for Peripheral Self–Nonself Discrimination

PubMed Central

Bretscher, P A

2014-01-01

The establishment of central tolerance to most self-antigens results in a repertoire of mature peripheral lymphocytes specific for foreign and peripheral self-antigens. The framework that single, mature lymphocytes are inactivated by antigen, whereas their activation requires lymphocyte cooperation, accounts for diverse observations and incorporates a mechanism of peripheral tolerance. This framework accounts for the generalizations that the sustained activation by antigen of most B cells and CD8 T cells requires CD4 T helper cells; in the absence of CD4 T cells, antigen can inactivate these B cells and CD8 T cells. In this sense, CD4 T cells are the guardians of the fate of most B cells and CD8 T cells when they encounter antigen. I argue here that the single-lymphocyte/multiple-lymphocyte framework for the inactivation/activation of lymphocytes also applies to CD4 T cells. I consider within this framework a model for the activation/inactivation of CD4 T cells that is consistent with the large majority of contemporary observations, including significant clinical observations. I outline the grounds why I feel this model is more plausible than the contemporary and predominant pathogen-associated molecular pattern (PAMP) and Danger Models for CD4 T cell activation. These models are based upon what I consider the radical premise that self–nonself discrimination does not exist at the level of mature CD4 T cells. I explain why I feel this feature renders the PAMP and Danger Models somewhat implausible. The model I propose, in contrast, is conservative in that it embodies such a process of self–nonself discrimination. PMID:24684567

Dissociable processes for orientation discrimination learning and contextual illusion magnitude.

PubMed

Wilks, Charlotte Elizabeth Holmes; Rees, Geraint; Schwarzkopf, Dietrich Samuel

2014-01-01

Previous research suggests an inverse relationship between human orientation discrimination sensitivity and tilt illusion magnitude. To test whether these perceptual functions are inherently linked, we measured both orientation discrimination sensitivity and the magnitude of the tilt illusion before and after participants had been trained for three days on an orientation discrimination task. Discrimination sensitivity improved with training and this improvement remained one month after the initial learning. However, tilt illusion magnitude remained unchanged before and after orientation training, at either trained or untrained orientations. Our results suggest that orientation discrimination sensitivity and illusion magnitude are not inherently linked. They also provide further evidence that, at least for the training periods we employed, perceptual learning of orientation discrimination may involve high-level processes.

Dissociable Processes for Orientation Discrimination Learning and Contextual Illusion Magnitude

PubMed Central

Wilks, Charlotte Elizabeth Holmes; Rees, Geraint; Schwarzkopf, Dietrich Samuel

2014-01-01

Previous research suggests an inverse relationship between human orientation discrimination sensitivity and tilt illusion magnitude. To test whether these perceptual functions are inherently linked, we measured both orientation discrimination sensitivity and the magnitude of the tilt illusion before and after participants had been trained for three days on an orientation discrimination task. Discrimination sensitivity improved with training and this improvement remained one month after the initial learning. However, tilt illusion magnitude remained unchanged before and after orientation training, at either trained or untrained orientations. Our results suggest that orientation discrimination sensitivity and illusion magnitude are not inherently linked. They also provide further evidence that, at least for the training periods we employed, perceptual learning of orientation discrimination may involve high-level processes. PMID:25061816

Evidence of Taxa-, Clone-, and Kin-discrimination in Protists: Ecological and Evolutionary Implications.

PubMed

Espinosa, Avelina; Paz-Y-Miño-C, Guillermo

2014-11-01

Unicellular eukaryotes, or protists, are among the most ancient organisms on Earth. Protists belong to multiple taxonomic groups; they are widely distributed geographically and in all environments. Their ability to discriminate among con- and heterospecifics has been documented during the past decade. Here we discuss exemplar cases of taxa-, clone-, and possible kin-discrimination in five major lineages: Mycetozoa ( Dictyostelium , Polysphondylium ), Dikarya ( Saccharomyces ), Ciliophora ( Tetrahymena ), Apicomplexa ( Plasmodium ) and Archamoebae ( Entamoeba ). We summarize the proposed genetic mechanisms involved in discrimination-mediated aggregation (self versus different), including the csA , FLO and trg (formerly lag ) genes, and the Proliferation Activation Factors (PAFs), which facilitate clustering in some protistan taxa. We caution about the experimental challenges intrinsic to studying recognition in protists, and highlight the opportunities for exploring the ecology and evolution of complex forms of cell-cell communication, including social behavior, in a polyphyletic, still superficially understood group of organisms. Because unicellular eukaryotes are the evolutionary precursors of multicellular life, we infer that their mechanisms of taxa-, clone-, and possible kin-discrimination gave origin to the complex diversification and sophistication of traits associated with species and kin recognition in plants, fungi, invertebrates and vertebrates.

Evidence of Taxa-, Clone-, and Kin-discrimination in Protists: Ecological and Evolutionary Implications

PubMed Central

Espinosa, Avelina; Paz-y-Miño-C, Guillermo

2014-01-01

Unicellular eukaryotes, or protists, are among the most ancient organisms on Earth. Protists belong to multiple taxonomic groups; they are widely distributed geographically and in all environments. Their ability to discriminate among con- and heterospecifics has been documented during the past decade. Here we discuss exemplar cases of taxa-, clone-, and possible kin-discrimination in five major lineages: Mycetozoa (Dictyostelium, Polysphondylium), Dikarya (Saccharomyces), Ciliophora (Tetrahymena), Apicomplexa (Plasmodium) and Archamoebae (Entamoeba). We summarize the proposed genetic mechanisms involved in discrimination-mediated aggregation (self versus different), including the csA, FLO and trg (formerly lag) genes, and the Proliferation Activation Factors (PAFs), which facilitate clustering in some protistan taxa. We caution about the experimental challenges intrinsic to studying recognition in protists, and highlight the opportunities for exploring the ecology and evolution of complex forms of cell-cell communication, including social behavior, in a polyphyletic, still superficially understood group of organisms. Because unicellular eukaryotes are the evolutionary precursors of multicellular life, we infer that their mechanisms of taxa-, clone-, and possible kin-discrimination gave origin to the complex diversification and sophistication of traits associated with species and kin recognition in plants, fungi, invertebrates and vertebrates. PMID:25400313

Prediction of hospital failure: a post-PPS analysis.

PubMed

Gardiner, L R; Oswald, S L; Jahera, J S

1996-01-01

This study investigates the ability of discriminant analysis to provide accurate predictions of hospital failure. Using data from the period following the introduction of the Prospective Payment System, we developed discriminant functions for each of two hospital ownership categories: not-for-profit and proprietary. The resulting discriminant models contain six and seven variables, respectively. For each ownership category, the variables represent four major aspects of financial health (liquidity, leverage, profitability, and efficiency) plus county marketshare and length of stay. The proportion of closed hospitals misclassified as open one year before closure does not exceed 0.05 for either ownership type. Our results show that discriminant functions based on a small set of financial and nonfinancial variables provide the capability to predict hospital failure reliably for both not-for-profit and proprietary hospitals.

Persistence and withdrawal by students in a preservice science and mathematics teacher education course

NASA Astrophysics Data System (ADS)

Tulip, David F.; Lucas, Keith B.

1991-12-01

At a time when recruitment into preservice teacher education courses in mathematics and science is difficult, one strategy to increase the number of graduates is to minimise the number of students who fail to complete their university courses. This study sought to determine factors which distinguish withdrawers from persisters in the first semester of a B.Ed course. Discriminant analysis was employed; a discriminant function employing seven factors resulted in correct classification in 81% of cases. Further analysis distinguishing between dropouts and transferees resulted in two discriminant functions with some common variables.

Associations between race-based and sex-based discrimination, health, and functioning: a longitudinal study of Marines.

PubMed

Foynes, Melissa M; Smith, Brian N; Shipherd, Jillian C

2015-04-01

Only a few studies have examined race-based discrimination (RBD) and sex-based discrimination (SBD) in military samples and all are cross-sectional. The current study examined associations between both RBD and SBD experienced during Marine recruit training and several health and functioning outcomes 11 years later in a racially/ethnically diverse sample of men and women. Linear multiple regression models were used to examine associations between sex, race/ethnicity, RBD and SBD, and later outcomes (physical health, self-esteem, and occupational/vocational functioning), accounting for baseline levels and covariates. Data were drawn from a larger longitudinal investigation of US Marine Corps recruits. The sample (N=471) was comprised of white men (34.6%), white women (37.6%), racial/ethnic minority men (12.7%), and racial/ethnic minority women (15.1%). Self-report measures of sex and race (T1), RBD and SBD (T2), social support (T2), mental health (T2), physical health (T2 and T5), self-esteem (T2 and T5), and occupational/vocational functioning (T5) were included. Over a decade later, experiences of RBD were negatively associated with physical health and self-esteem. Social support was the strongest predictor of occupational/vocational functioning. Effects of sex, SBD, and minority status were not significant in regressions after accounting for other variables. Health care providers can play a key role in tailoring care to the needs of these important subpopulations of veterans by assessing and acknowledging experiences of discrimination and remaining aware of the potential negative associations between discrimination and health and functioning above and beyond the contributions of sex and race/ethnicity.

Spatiotemporal dynamics of neocortical excitation and inhibition during human sleep.

PubMed

Peyrache, Adrien; Dehghani, Nima; Eskandar, Emad N; Madsen, Joseph R; Anderson, William S; Donoghue, Jacob A; Hochberg, Leigh R; Halgren, Eric; Cash, Sydney S; Destexhe, Alain

2012-01-31

Intracranial recording is an important diagnostic method routinely used in a number of neurological monitoring scenarios. In recent years, advancements in such recordings have been extended to include unit activity of an ensemble of neurons. However, a detailed functional characterization of excitatory and inhibitory cells has not been attempted in human neocortex, particularly during the sleep state. Here, we report that such feature discrimination is possible from high-density recordings in the neocortex by using 2D multielectrode arrays. Successful separation of regular-spiking neurons (or bursting cells) from fast-spiking cells resulted in well-defined clusters that each showed unique intrinsic firing properties. The high density of the array, which allowed recording from a large number of cells (up to 90), helped us to identify apparent monosynaptic connections, confirming the excitatory and inhibitory nature of regular-spiking and fast-spiking cells, thus categorized as putative pyramidal cells and interneurons, respectively. Finally, we investigated the dynamics of correlations within each class. A marked exponential decay with distance was observed in the case of excitatory but not for inhibitory cells. Although the amplitude of that decline depended on the timescale at which the correlations were computed, the spatial constant did not. Furthermore, this spatial constant is compatible with the typical size of human columnar organization. These findings provide a detailed characterization of neuronal activity, functional connectivity at the microcircuit level, and the interplay of excitation and inhibition in the human neocortex.

Personal discrimination and satisfaction with life: Exploring perceived functional effects of Asian American race/ethnicity as a moderator.

PubMed

Tran, Alisia G T T; Sangalang, Cindy C

2016-01-01

This study aims to understand the relations between experiences of racial/ethnic discrimination, perceptions of the harmful or helpful effects of one's Asian American race/ethnicity within educational and occupational contexts (perceived functional effects), and well-being (i.e., satisfaction with life). A primary focus was to evaluate whether the association between racial/ethnic discrimination and satisfaction with life varied based on the degree to which Asian Americans believe that their race or ethnicity is helpful or harmful to educational and occupational functioning. This study draws on nationally representative data from ethnically diverse Asian American adults (N = 3,335) and utilizes weighted descriptive, correlational, and logistic regression moderation analyses. Ethnic variations emerged across analyses. Logistic regression analyses revealed a significant moderation effect for Chinese and Filipino Americans. Follow-up analyses revealed a protective effect of perceiving more positive or helpful functional effects in nullifying the link between discrimination and dissatisfaction with life for Chinese Americans. By contrast, viewing more harmful functional effects had a buffering effect for Filipino Americans. Results have implications for conceptualizing the potential impact of perspectives that imply Asian American advantage or disadvantage. Opportunities to apply and extend these initial findings are discussed. (c) 2016 APA, all rights reserved).

Racial Discrimination: A Continuum of Violence Exposure for Children of Color

ERIC Educational Resources Information Center

Sanders-Phillips, Kathy

2009-01-01

This article reviews and examines findings on the impact of racial discrimination on the development and functioning of children of color in the US. Based on current definitions of violence and child maltreatment, exposure to racial discrimination should be considered as a form of violence that can significantly impact child outcomes and limit the…

Intact Visual Discrimination of Complex and Feature-Ambiguous Stimuli in the Absence of Perirhinal Cortex

ERIC Educational Resources Information Center

Squire, Larry R.; Levy, Daniel A.; Shrager, Yael

2005-01-01

The perirhinal cortex is known to be important for memory, but there has recently been interest in the possibility that it might also be involved in visual perceptual functions. In four experiments, we assessed visual discrimination ability and visual discrimination learning in severely amnesic patients with large medial temporal lobe lesions that…

Perceived Racial/Ethnic Discrimination and Adjustment among Ethnically Diverse College Students: Family and Peer Support as Protective Factors

ERIC Educational Resources Information Center

Juang, Linda; Ittel, Angela; Hoferichter, Frances; Gallarin, Miriam

2016-01-01

Adopting a risk and resilience perspective, the current study examined whether family cohesion and peer support functioned as protective factors against the negative effects of racial/ethnic discrimination by peers. The sample included 142 ethnically diverse college students. The results showed that while greater perceived discrimination was…

A Functional Near-Infrared Spectroscopy Study of Sustained Attention to Local and Global Target Features

ERIC Educational Resources Information Center

De Joux, Neil; Russell, Paul N.; Helton, William S.

2013-01-01

Despite a long history of vigilance research, the role of global and local feature discrimination in vigilance tasks has been relatively neglected. In this experiment participants performed a sustained attention task requiring either global or local shape stimuli discrimination. Reaction time to local feature discriminations was characterized by a…

Sensory Discrimination, Working Memory and Intelligence in 9-Year-Old and 11-Year-Old Children

ERIC Educational Resources Information Center

Voelke, Annik E.; Troche, Stefan J.; Rammsayer, Thomas H.; Wagner, Felicitas L.; Roebers, Claudia M.

2013-01-01

More than a century ago, Galton and Spearman suggested that there was a functional relationship between sensory discrimination ability and intelligence. Studies have since been able to confirm a close relationship between general discrimination ability (GDA) and IQ. The aim of the present study was to assess whether this strong relationship…

School-Based Racial and Gender Discrimination among African American Adolescents: Exploring Gender Variation in Frequency and Implications for Adjustment

PubMed Central

Chavous, Tabbye M.; Griffin, Tiffany M.

2012-01-01

The present study examined school-based racial and gender discrimination experiences among African American adolescents in Grade 8 (n = 204 girls; n = 209 boys). A primary goal was exploring gender variation in frequency of both types of discrimination and associations of discrimination with academic and psychological functioning among girls and boys. Girls and boys did not vary in reported racial discrimination frequency, but boys reported more gender discrimination experiences. Multiple regression analyses within gender groups indicated that among girls and boys, racial discrimination and gender discrimination predicted higher depressive symptoms and school importance and racial discrimination predicted self-esteem. Racial and gender discrimination were also negatively associated with grade point average among boys but were not significantly associated in girls’ analyses. Significant gender discrimination X racial discrimination interactions resulted in the girls’ models predicting psychological outcomes and in boys’ models predicting academic achievement. Taken together, findings suggest the importance of considering gender- and race-related experiences in understanding academic and psychological adjustment among African American adolescents. PMID:22837794

School-Based Racial and Gender Discrimination among African American Adolescents: Exploring Gender Variation in Frequency and Implications for Adjustment.

PubMed

Cogburn, Courtney D; Chavous, Tabbye M; Griffin, Tiffany M

2011-01-03

The present study examined school-based racial and gender discrimination experiences among African American adolescents in Grade 8 (n = 204 girls; n = 209 boys). A primary goal was exploring gender variation in frequency of both types of discrimination and associations of discrimination with academic and psychological functioning among girls and boys. Girls and boys did not vary in reported racial discrimination frequency, but boys reported more gender discrimination experiences. Multiple regression analyses within gender groups indicated that among girls and boys, racial discrimination and gender discrimination predicted higher depressive symptoms and school importance and racial discrimination predicted self-esteem. Racial and gender discrimination were also negatively associated with grade point average among boys but were not significantly associated in girls' analyses. Significant gender discrimination X racial discrimination interactions resulted in the girls' models predicting psychological outcomes and in boys' models predicting academic achievement. Taken together, findings suggest the importance of considering gender- and race-related experiences in understanding academic and psychological adjustment among African American adolescents.

Gene stage-specific expression in the microenvironment of pediatric myelodysplastic syndromes.

PubMed

Roela, Rosimeire A; Carraro, Dirce M; Brentani, Helena P; Kaiano, Jane H L; Simão, Daniel F; Guarnieiro, Roberto; Lopes, Luiz Fernando; Borojevic, Radovan; Brentani, M Mitzi

2007-05-01

Using cDNA microarray assays we have observed a clear difference in the gene expression pattern between bone marrow stromal cells obtained from healthy children (CT) and from pediatric patients with either myelodysplastic syndromes (MDS) or acute myeloid leukemia (AML) associated with MDS (MDS-AML). The global gene function profiling analysis indicated that in the pediatric MDS microenvironment the disease stages may be characterized mainly by underexpression of genes associated with biological processes such as transport. Furthermore, a subset of downregulated genes related to endocytosis and protein secretion was able to discriminate MDS from MDS-AML.

The number of functional olfactory receptor genes and the relative size of olfactory brain structures are poor predictors of olfactory discrimination performance with enantiomers.

PubMed

Laska, Matthias; Genzel, Daria; Wieser, Alexandra

2005-02-01

The ability of four squirrel monkeys and three pigtail macaques to distinguish between nine enantiomeric odor pairs sharing an isopropenyl group at the chiral center was investigated in terms of a conditioning paradigm. All animals from both species were able to discriminate between the optical isomers of limonene, carvone, dihydrocarvone, dihydrocarveole and dihydrocarvyl acetate, whereas they failed to distinguish between the (+)- and (-)-forms of perillaaldehyde and limonene oxide. The pigtail macaques, but not the squirrel monkeys, also discriminated between the antipodes of perillaalcohol and isopulegol. A comparison of the across-task patterns of discrimination performance shows a high degree of similarity among the two primate species and also between these nonhuman primates and human subjects tested in an earlier study on the same tasks. These findings suggest that between-species comparisons of the relative size of olfactory brain structures or of the number of functional olfactory receptor genes are poor predictors of olfactory discrimination performance with enantiomers.

Local kernel nonparametric discriminant analysis for adaptive extraction of complex structures

NASA Astrophysics Data System (ADS)

Li, Quanbao; Wei, Fajie; Zhou, Shenghan

2017-05-01

The linear discriminant analysis (LDA) is one of popular means for linear feature extraction. It usually performs well when the global data structure is consistent with the local data structure. Other frequently-used approaches of feature extraction usually require linear, independence, or large sample condition. However, in real world applications, these assumptions are not always satisfied or cannot be tested. In this paper, we introduce an adaptive method, local kernel nonparametric discriminant analysis (LKNDA), which integrates conventional discriminant analysis with nonparametric statistics. LKNDA is adept in identifying both complex nonlinear structures and the ad hoc rule. Six simulation cases demonstrate that LKNDA have both parametric and nonparametric algorithm advantages and higher classification accuracy. Quartic unilateral kernel function may provide better robustness of prediction than other functions. LKNDA gives an alternative solution for discriminant cases of complex nonlinear feature extraction or unknown feature extraction. At last, the application of LKNDA in the complex feature extraction of financial market activities is proposed.

Influence of sensitization on the discriminative stimulus effects of methylphenidate in mice.

PubMed

McGovern, Robin; Luderman, Lauryn; Knecht, Kelly; Griffin, William C

2014-12-01

Methylphenidate (MPH) remains an important therapy for attention-deficit hyperactivity disorder, but aspects of its pharmacology remain unclear. In the present study, we used a regimen of MPH (8 mg/kg daily×14 days) in C57BL/6J mice to determine whether establishing locomotor sensitization to MPH influenced the acquisition and the dose-response function of MPH in a classic drug discrimination procedure. MPH-sensitized mice (SENS group) showed enhanced locomotor activity to the 8 mg/kg exposure dose as well as a 2 mg/kg dose before discrimination training. However, the SENS mice did not acquire discrimination of either a low dose (2 mg/kg) or a higher dose (4 mg/kg) of MPH any more rapidly than the CTRL mice. Further, during generalization testing, the dose-response functions for the SENS and CTRL mice were identical. Therefore, we did not find that previous exposure to MPH, which produced a sensitized locomotor response, facilitated MPH discrimination.

The discrimination of fish egg quality and viability by using Raman spectroscopy

NASA Astrophysics Data System (ADS)

Ishigaki, Mika; Sato, Hidetoshi

2014-03-01

Sexual reproductive body can be produced from a fertilized ovum. Once the ovum is fertilized with sperm, it runs through the cell division, differentiates to all kinds of cells, and goes to make a complete body. However, not all of them are viable and some of them stop to ontogenesis showing the developmental abnormality. In order to discriminate the egg quality, we apply Raman spectroscopy for fish egg. After the measurement, these Raman data are checked up with the information about the eggs can survive or not, and we examine what factors are important in egg components to distinguish between "good quality" and "not good quality". We present the results of assessment of egg quality, and investigate whether Raman spectroscopy can be used to a discriminate of egg quality.

Multi-Site Diagnostic Classification of Schizophrenia Using Discriminant Deep Learning with Functional Connectivity MRI.

PubMed

Zeng, Ling-Li; Wang, Huaning; Hu, Panpan; Yang, Bo; Pu, Weidan; Shen, Hui; Chen, Xingui; Liu, Zhening; Yin, Hong; Tan, Qingrong; Wang, Kai; Hu, Dewen

2018-04-01

A lack of a sufficiently large sample at single sites causes poor generalizability in automatic diagnosis classification of heterogeneous psychiatric disorders such as schizophrenia based on brain imaging scans. Advanced deep learning methods may be capable of learning subtle hidden patterns from high dimensional imaging data, overcome potential site-related variation, and achieve reproducible cross-site classification. However, deep learning-based cross-site transfer classification, despite less imaging site-specificity and more generalizability of diagnostic models, has not been investigated in schizophrenia. A large multi-site functional MRI sample (n = 734, including 357 schizophrenic patients from seven imaging resources) was collected, and a deep discriminant autoencoder network, aimed at learning imaging site-shared functional connectivity features, was developed to discriminate schizophrenic individuals from healthy controls. Accuracies of approximately 85·0% and 81·0% were obtained in multi-site pooling classification and leave-site-out transfer classification, respectively. The learned functional connectivity features revealed dysregulation of the cortical-striatal-cerebellar circuit in schizophrenia, and the most discriminating functional connections were primarily located within and across the default, salience, and control networks. The findings imply that dysfunctional integration of the cortical-striatal-cerebellar circuit across the default, salience, and control networks may play an important role in the "disconnectivity" model underlying the pathophysiology of schizophrenia. The proposed discriminant deep learning method may be capable of learning reliable connectome patterns and help in understanding the pathophysiology and achieving accurate prediction of schizophrenia across multiple independent imaging sites. Copyright © 2018 German Center for Neurodegenerative Diseases (DZNE). Published by Elsevier B.V. All rights reserved.

Osmophobia and olfactory functions in patients with migraine.

PubMed

Kayabaşoglu, Gürkan; Altundag, Aytug; Kotan, Dilcan; Dizdar, Denizhan; Kaymaz, Recep

2017-02-01

Olfactory dysfunction and migraine has been associated for a long time. In this study, we planned to compare olfactory functions in patients with migraine and osmophobia with patients having migraine but no osmophobia, in addition with a normal control group using "Sniffin' Sticks" test. The main distinction of this study is that all qualitative and quantitative properties of olfactory functions; threshold, discrimination and identification, are evaluated separately and jointly. Thirty healthy person aged between 16 and 56 (18 women, 12 men) and 60 migraine patients aged between 15 and 54 (39 women, 21 man) were included in the study. All patients have been inquired about osmophobia and have been assessed with Hedonic tone assessment. Osmophobia has been tested for perfume, cigarette smoke, leather, stale food, soy sauce, fish, spices and coffee smells. Olfactory functions has been assessed with "Sniffin' Sticks" smell test. Thresholds, discrimination and identification have been determined for each patient. In migraine patients with osmophobia, threshold was 7.75 ± 2.3, in migraine patients without osmophobia threshold was 8.25 ± 1.5 and threshold was 10.75 ± 1.3 for the control group. Discrimination score was 6 ± 1.2 in migraine patients with osmophobia, 9 ± 0.8 in patients without osmophobia and was 12 ± 1.4 in the control group. In migraine patient with or without osmophobia Threshold/Discrimination/Identification (TDI) scores were lower than the control group. The most important parameter in our study is that discrimination scores were especially lower in patients with osmophobia. We believe that this decrease in discrimination in migraine patients with osmophobia; who claim that they smell everything and they are sensitive to all smells, is significant. Further studies about smell discrimination will help better understand some conditions; especially anosmia and hyposmia after upper respiratory tract infections and parosmia.

Can performance of daily activities discriminate between older adults with normal cognitive function and those with Mild Cognitive Impairment?

PubMed Central

Rodakowski, Juleen; Skidmore, Elizabeth R.; Reynolds, Charles F.; Dew, Mary Amanda; Butters, Meryl A.; Holm, Margo B.; Lopez, Oscar L.; Rogers, Joan C.

2014-01-01

OBJECTIVES Our primary aim was to examine whether preclinical disability in performance of cognitively-focused instrumental activities of daily living (C-IADL) tasks can discriminate between older adults with normal cognitive function and those with Mild Cognitive Impairment (MCI). The secondary purpose was to determine the two tasks with the strongest psychometric properties and assess their discriminative ability. Our goal was to generate diagnosis-relevant information about cognitive changes associated with MCI and DSM-5 Mild Neurocognitive Disorder. DESIGN Secondary analyses of cross-sectional data from a cohort of individuals diagnosed with normal cognitive function or MCI. SETTING Private home locations in Pittsburgh, PA. PARTICIPANTS Older adults with remitted major depression (N=157). MEASUREMENTS Diagnosis of cognitive status was made by the Alzheimer’s Disease Research Center at the University of Pittsburgh. Performance of 8 C-IADL was measured using the criterion-referenced, observation-based Performance Assessment of Self-Care Skills (PASS). RESULTS A total of 96 older adults with normal cognitive function (mean age=72.5, SD=5.9) and 61 older adults with MCI (mean age=75.5, SD=6.3) participated. The 8 C-IADL demonstrated 81% accuracy in discriminating cognitive status (area under curve 0.81, p<0.001). Two tasks (shopping and checkbook balancing) were the most discriminating (area under curve 0.80, p<0.001); they demonstrated similar ability, as the 8 C-IADL, to discriminate cognitive status. Assessing performance on these two C-IADL takes 10–15 minutes. CONCLUSION This is the first demonstration of the discriminative ability of preclinical disability in distinguishing MCI from cognitively normal older adults. These findings highlight potential tasks, when measured with the observation-based PASS, which demonstrate increased effort for individuals with MCI. These tasks may be considered when attempting to diagnose MCI or Mild Neurocognitive Disorder in clinical practice and research. PMID:24890517

Ring-Shaped Microlanes and Chemical Barriers as a Platform for Probing Single-Cell Migration.

PubMed

Schreiber, Christoph; Segerer, Felix J; Wagner, Ernst; Roidl, Andreas; Rädler, Joachim O

2016-05-31

Quantification and discrimination of pharmaceutical and disease-related effects on cell migration requires detailed characterization of single-cell motility. In this context, micropatterned substrates that constrain cells within defined geometries facilitate quantitative readout of locomotion. Here, we study quasi-one-dimensional cell migration in ring-shaped microlanes. We observe bimodal behavior in form of alternating states of directional migration (run state) and reorientation (rest state). Both states show exponential lifetime distributions with characteristic persistence times, which, together with the cell velocity in the run state, provide a set of parameters that succinctly describe cell motion. By introducing PEGylated barriers of different widths into the lane, we extend this description by quantifying the effects of abrupt changes in substrate chemistry on migrating cells. The transit probability decreases exponentially as a function of barrier width, thus specifying a characteristic penetration depth of the leading lamellipodia. Applying this fingerprint-like characterization of cell motion, we compare different cell lines, and demonstrate that the cancer drug candidate salinomycin affects transit probability and resting time, but not run time or run velocity. Hence, the presented assay allows to assess multiple migration-related parameters, permits detailed characterization of cell motility, and has potential applications in cell biology and advanced drug screening.

Novel methods of time-resolved fluorescence data analysis for in-vivo tissue characterization: application to atherosclerosis.

PubMed

Jo, J A; Fang, Q; Papaioannou, T; Qiao, J H; Fishbein, M C; Dorafshar, A; Reil, T; Baker, D; Freischlag, J; Marcu, L

2004-01-01

This study investigates the ability of new analytical methods of time-resolved laser-induced fluorescence spectroscopy (TR-LIFS) data to characterize tissue in-vivo, such as the composition of atherosclerotic vulnerable plaques. A total of 73 TR-LIFS measurements were taken in-vivo from the aorta of 8 rabbits, and subsequently analyzed using the Laguerre deconvolution technique. The investigated spots were classified as normal aorta, thin or thick lesions, and lesions rich in either collagen or macrophages/foam-cells. Different linear and nonlinear classification algorithms (linear discriminant analysis, stepwise linear discriminant analysis, principal component analysis, and feedforward neural networks) were developed using spectral and TR features (ratios of intensity values and Laguerre expansion coefficients, respectively). Normal intima and thin lesions were discriminated from thick lesions (sensitivity >90%, specificity 100%) using only spectral features. However, both spectral and time-resolved features were necessary to discriminate thick lesions rich in collagen from thick lesions rich in foam cells (sensitivity >85%, specificity >93%), and thin lesions rich in foam cells from normal aorta and thin lesions rich in collagen (sensitivity >85%, specificity >94%). Based on these findings, we believe that TR-LIFS information derived from the Laguerre expansion coefficients can provide a valuable additional dimension for in-vivo tissue characterization.

Age-related functional changes in domain-specific medial temporal lobe pathways.

PubMed

Berron, David; Neumann, Katja; Maass, Anne; Schütze, Hartmut; Fliessbach, Klaus; Kiven, Verena; Jessen, Frank; Sauvage, Magdalena; Kumaran, Dharshan; Düzel, Emrah

2018-05-01

There is now converging evidence from studies in animals and humans that the medial temporal lobes (MTLs) harbor anatomically distinct processing pathways for object and scene information. Recent functional magnetic resonance imaging studies in humans suggest that this domain-specific organization may be associated with a functional preference of the anterior-lateral part of the entorhinal cortex (alErC) for objects and the posterior-medial entorhinal cortex (pmErC) for scenes. As MTL subregions are differentially affected by aging and neurodegenerative diseases, the question was raised whether aging may affect the 2 pathways differentially. To address this possibility, we developed a paradigm that allows the investigation of object memory and scene memory in a mnemonic discrimination task. A group of young (n = 43) and healthy older subjects (n = 44) underwent functional magnetic resonance imaging recordings during this novel task, while they were asked to discriminate exact repetitions of object and scene stimuli from novel stimuli that were similar but modified versions of the original stimuli ("lures"). We used structural magnetic resonance images to manually segment anatomical components of the MTL including alErC and pmErC and used these segmented regions to analyze domain specificity of functional activity. Across the entire sample, object processing was associated with activation of the perirhinal cortex (PrC) and alErC, whereas for scene processing, activation was more predominant in the parahippocampal cortex and pmErC. Functional activity related to mnemonic discrimination of object and scene lures from exact repetitions was found to overlap between processing pathways and suggests that while the PrC-alErC pathway was more involved in object discrimination, both pathways were involved in the discrimination of similar scenes. Older adults were behaviorally less accurate than young adults in discriminating similar lures from exact repetitions, but this reduction was equivalent in both domains. However, this was accompanied by significantly reduced domain-specific activity in PrC in older adults compared to what was observed in the young. Furthermore, this reduced domain-specific activity was associated to worse performance in object mnemonic discrimination in older adults. Taken together, we show the fine-grained functional organization of the MTL into domain-specific pathways for objects and scenes and their mnemonic discrimination and further provide evidence that aging might affect these pathways in a differential fashion. Future experiments will elucidate whether the 2 pathways are differentially affected in early stages of Alzheimer's disease in relation to amyloid or tau pathology. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

Further studies of crania from ancient northern Africa: an analysis of crania from first dynasty Egyptian tombs, using discriminant functions.

PubMed

Keita, S O

1992-03-01

An analysis of First Dynasty crania from Abydos was undertaken using multiple discriminant functions. The results demonstrate greater affinity with Upper Nile Valley patterns, but also suggest change from earlier craniometric trends. Gene flow and movement of northern officials to the important southern city may explain the findings.

AFRRI (Armed Forces Radiobiology Research Institute) reports, October, January-March 1989. Technical report

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

Not Available

1989-01-01

Contents include: effects of ethiofos (WR-2721) and radiation on monkey visual discrimination performance; gamma radiolysis of RNA: an ESR and spin-trapping study; phospholipid storage in the secretory granule of the mast cell; physiological localization of an agonist-sensitive pool of Ca{sup 2+} in parotid acinar cells; changes in canine neutrophil function(s) following cellular isolation by percoll gradient centrifugation or isotoniclysis; impaired repair of uvc-induced DNA damage in l5178Y-R cells: sedimentation studies with the use of 5'-bromodeoxyuridine photolysis; comparative behavioral toxicity of four sulfhydryl radioprotective compounds in mice: WR-2721, cysteamine, diethyldithiocarbamate, and n-acetylcysteine; measurement of the radiosensitivity of rat marrow by flowmore » cytometry; radioprotection by biological response modifiers alone and in combination with WR-2721; postirradiation glucan administration enhances the radioprotective effects of WR-2721; attenuation and cross-attenuation in taste aversion learning in the rat: studies with ionizing radiation, lithium chloride, and ethanol; a low-energy x-ray irradiator for electrophysiological studies; thermospray liquid chromatography mass spectrometry of thiol radioprotective agents: characteristic spectra; radioprotection by leukotrienes: is there a receptor mechanism and a low-energy x-ray irradiator for electrophysiological studies.« less

Classification of lung cancer histology by gold nanoparticle sensors

PubMed Central

Barash, Orna; Peled, Nir; Tisch, Ulrike; Bunn, Paul A.; Hirsch, Fred R.; Haick, Hossam

2016-01-01

We propose a nanomedical device for the classification of lung cancer (LC) histology. The device profiles volatile organic compounds (VOCs) in the headspace of (subtypes of) LC cells, using gold nanoparticle (GNP) sensors that are suitable for detecting LC-specific patterns of VOC profiles, as determined by gas chromatography–mass spectrometry analysis. Analyzing the GNP sensing signals by support vector machine allowed significant discrimination between (i) LC and healthy cells; (ii) small cell LC and non–small cell LC; and between (iii) two subtypes of non–small cell LC: adenocarcinoma and squamous cell carcinoma. The discriminative power of the GNP sensors was then linked with the chemical nature and composition of the headspace VOCs of each LC state. These proof-of-concept findings could totally revolutionize LC screening and diagnosis, and might eventually allow early and differential diagnosis of LC subtypes with detectable or unreachable lung nodules. PMID:22033081

Chromatin interaction networks revealed unique connectivity patterns of broad H3K4me3 domains and super enhancers in 3D chromatin.

PubMed

Thibodeau, Asa; Márquez, Eladio J; Shin, Dong-Guk; Vera-Licona, Paola; Ucar, Duygu

2017-10-31

Broad domain promoters and super enhancers are regulatory elements that govern cell-specific functions and harbor disease-associated sequence variants. These elements are characterized by distinct epigenomic profiles, such as expanded deposition of histone marks H3K27ac for super enhancers and H3K4me3 for broad domains, however little is known about how they interact with each other and the rest of the genome in three-dimensional chromatin space. Using network theory methods, we studied chromatin interactions between broad domains and super enhancers in three ENCODE cell lines (K562, MCF7, GM12878) obtained via ChIA-PET, Hi-C, and Hi-CHIP assays. In these networks, broad domains and super enhancers interact more frequently with each other compared to their typical counterparts. Network measures and graphlets revealed distinct connectivity patterns associated with these regulatory elements that are robust across cell types and alternative assays. Machine learning models showed that these connectivity patterns could effectively discriminate broad domains from typical promoters and super enhancers from typical enhancers. Finally, targets of broad domains in these networks were enriched in disease-causing SNPs of cognate cell types. Taken together these results suggest a robust and unique organization of the chromatin around broad domains and super enhancers: loci critical for pathologies and cell-specific functions.

Evaluation of Vitality in the Experimental Hanging Model of Rats by Using Immunohistochemical IL-1β Antibody Staining.

PubMed

Balandiz, Hüseyin; Pehlivan, Sultan; Çiçek, Ali Fuat; Tuğcu, Harun

2015-12-01

Hanging is the most common suicide method in the world, and the discrimination of antemortem-postmortem hanging must be done at autopsy. The aim of this experimental study was to examine the immunohistochemical expression of IL-1β antibody at the hanging mark skin samples of rats to discriminate antemortem and postmortem hangings. A total of 20 Wistar albino rats were used for this study. The groups were as follows: A-1, antemortem control group; A-2, antemortem second-hour hanging mark skin samples; A-3, antemortem 24th-hour hanging mark skin samples; A-4, antemortem 72nd-hour hanging mark skin samples; B-1, postmortem control group; and B-2, postmortem second-hour hanging mark skin samples. Interleukin-1β immunostaining was performed to all tissue samples. For epidermal cells, group A-1 samples did not show IL-1β immunostaining, group A-2 samples were severely immunostained, and groups A-3 and A-4 samples' staining were slightly decreased. There was no IL-1β antibody staining in groups B-1 and B-2 samples. For adnexal cells, groups A-1 and B-1 samples did not show IL-1β immunostaining, staining of group A-2 samples was mild to severe, and groups A-3 and A-4 samples' staining were slightly decreased. Half of the group B-2 samples did not show IL-1β immunostaining. For subepidermal cells, most of the samples of groups A-1 and B-1 showed slight immunostaining, groups A-2 and B-2 samples' staining were mild to severe, and there were slight immunostaining in groups A-3 and A-4 samples. The majority of vascular structure cells did not show IL-1β immunostaining. Interleukin-1β immunostaining of epidermal cells can discriminate antemortem-postmortem hangings, but vascular structure cells and subepidermal cells cannot discriminate vital hangings.

Strength in numbers? Cognitive reappraisal tendencies and psychological functioning among Latinos in the context of oppression.

PubMed

Soto, José A; Armenta, Brian E; Perez, Christopher R; Zamboanga, Byron L; Umaña-Taylor, Adriana J; Lee, Richard M; Schwartz, Seth J; Park, Irene J K; Huynh, Que-Lam; Whitbourne, Susan Krauss; Le, Thao N; Ham, Lindsay S

2012-10-01

The typically positive relationship between cognitive reappraisal and psychological functioning may be nullified for Latinos embedded within multiple contexts of oppression (Perez & Soto, 2011). Multiply oppressive contexts are characterized by exposure to oppression at a societal level (distal oppression), in the immediate environment (proximal oppression), and at an individual level (personal oppression). We replicated and extended Perez and Soto's (2011) findings by examining whether the reappraisal-psychological functioning association was moderated by (a) relative numerical representation of Latinos within the environment (proximal oppression) and (b) personal perceptions of discrimination (personal oppression) among 425 Latino college students throughout the United States. For Latinos in high-Latino counties, greater use of reappraisal was associated with better psychological functioning, regardless of perceived discrimination; this relationship was absent for Latinos in low-Latino counties who perceived greater discrimination. Findings highlight the importance of considering how contextual factors can alter the adaptive functions of emotion regulation strategies.

Effects of onboard insecticide use on airline flight attendants.

PubMed

Kilburn, Kaye H

2004-06-01

Flight attendants (FAs) exposed to insecticide spray in an aircraft were compared with unexposed subjects for neurobehavioral function, pulmonary function, mood states, and symptoms. The 33 symptomatic FAs were self-selected, and 5 had retired for disability. Testing procedures included balance, reaction time, color discrimination, visual fields, grip strength, verbal recall, problem solving, attention and discrimination functions, and long-term memory functions. Measurements were expressed as a percentage of their predicted values (derived from unexposed controls), and the author compared the means of the percentage predicted values by analysis of variance. Symptom frequencies and Profile of Mood States (POMS) scores were assessed. FAs were significantly more impaired than controls with respect to balance with eyes closed, grip strength, and color discrimination. Nearly half had 3 or more abnormal neurobehavioral functions, after adjustment was made for age, sex, and education level. Neither elevated POMS scores nor frequencies of average symptoms correlated with their numbers of abnormal measurements. Occupational exposure to synthetic pyrethrin insecticides on airliners was associated with neurobehavioral impairment and disability retirement.

Radar detection with the Neyman-Pearson criterion using supervised-learning-machines trained with the cross-entropy error

NASA Astrophysics Data System (ADS)

Jarabo-Amores, María-Pilar; la Mata-Moya, David de; Gil-Pita, Roberto; Rosa-Zurera, Manuel

2013-12-01

The application of supervised learning machines trained to minimize the Cross-Entropy error to radar detection is explored in this article. The detector is implemented with a learning machine that implements a discriminant function, which output is compared to a threshold selected to fix a desired probability of false alarm. The study is based on the calculation of the function the learning machine approximates to during training, and the application of a sufficient condition for a discriminant function to be used to approximate the optimum Neyman-Pearson (NP) detector. In this article, the function a supervised learning machine approximates to after being trained to minimize the Cross-Entropy error is obtained. This discriminant function can be used to implement the NP detector, which maximizes the probability of detection, maintaining the probability of false alarm below or equal to a predefined value. Some experiments about signal detection using neural networks are also presented to test the validity of the study.

Bromovinyl-deoxyuridine: A selective substrate for mitochondrial thymidine kinase in cell extracts.

PubMed

Franzolin, Elisa; Rampazzo, Chiara; Pérez-Pérez, María-Jesús; Hernández, Ana-Isabel; Balzarini, Jan; Bianchi, Vera

2006-05-26

Cellular models of mitochondrial thymidine kinase (TK2) deficiency require a reliable method to measure TK2 activity in whole cell extracts containing two interfering deoxyribonucleoside kinases, thymidine kinase 1 (TK1) and deoxycytidine kinase. We tested the value of the thymidine analog (E)-5-(2-bromovinyl)-2'-deoxyuridine (BVDU) as a TK2-specific substrate. With extracts of OSTTK1- cells containing TK2 as the only thymidine kinase and a highly specific TK2 inhibitor we established conditions to detect the low TK2 activity commonly present in cells. With extracts of TK1-proficient osteosarcoma cells and normal human fibroblasts we showed that BVDU, but not 1-(beta-d-arabinofuranosyl)thymine (Ara-T), discriminates TK2 activity even in the presence of 100-fold excess TK1. A comparison with current procedures based on TK2 inhibition demonstrated the better performance of the new TK2 assay. When cultured human fibroblasts passed from proliferation to quiescence TK2 activity increased by 3-fold, stressing the importance of TK2 function in the absence of TK1.

Discrimination learning and attentional set formation in a mouse model of Fragile X.

PubMed

Casten, Kimberly S; Gray, Annette C; Burwell, Rebecca D

2011-06-01

Fragile X Syndrome is the most prevalent genetic cause of mental retardation. Selective deficits in executive function, including inhibitory control and attention, are core features of the disorder. In humans, Fragile X results from a trinucleotide repeat in the Fmr1 gene that renders it functionally silent and has been modeled in mice by targeted deletion of the Fmr1 gene. Fmr1 knockout (KO) mice recapitulate many features of Fragile X syndrome, but evidence for deficits in executive function is inconsistent. To address this issue, we trained wild-type and Fmr1 KO mice on an experimental paradigm that assesses attentional set-shifting. Mice learned to discriminate between stimuli differing in two of three perceptual dimensions. Successful discrimination required attending only to the relevant dimension, while ignoring irrelevant dimensions. Mice were trained on three discriminations in the same perceptual dimension, each followed by a reversal. This procedure normally results in the formation of an attentional set to the relevant dimension. Mice were then required to shift attention and discriminate based on a previously irrelevant perceptual dimension. Wild-type mice exhibited the increase in trials to criterion expected when shifting attention from one perceptual dimension to another. In contrast, the Fmr1 KO group failed to show the expected increase, suggesting impairment in forming an attentional set. Fmr1 KO mice also exhibited a general impairment in learning discriminations and reversals. This is the first demonstration that Fmr1 KO mice show a deficit in attentional set formation.

Isolation of Circulating Tumor Cells by Dielectrophoresis

PubMed Central

Gascoyne, Peter R. C.; Shim, Sangjo

2014-01-01

Dielectrophoresis (DEP) is an electrokinetic method that allows intrinsic dielectric properties of suspended cells to be exploited for discrimination and separation. It has emerged as a promising method for isolating circulation tumor cells (CTCs) from blood. DEP-isolation of CTCs is independent of cell surface markers. Furthermore, isolated CTCs are viable and can be maintained in culture, suggesting that DEP methods should be more generally applicable than antibody-based approaches. The aim of this article is to review and synthesize for both oncologists and biomedical engineers interested in CTC isolation the pertinent characteristics of DEP and CTCs. The aim is to promote an understanding of the factors involved in realizing DEP-based instruments having both sufficient discrimination and throughput to allow routine analysis of CTCs in clinical practice. The article brings together: (a) the principles of DEP; (b) the biological basis for the dielectric differences between CTCs and blood cells; (c) why such differences are expected to be present for all types of tumors; and (d) instrumentation requirements to process 10 mL blood specimens in less than 1 h to enable routine clinical analysis. The force equilibrium method of dielectrophoretic field-flow fractionation (DEP-FFF) is shown to offer higher discrimination and throughput than earlier DEP trapping methods and to be applicable to clinical studies. PMID:24662940

Construct validity of the PROMIS® sexual function and satisfaction measures in patients with cancer

PubMed Central

2013-01-01

Background With data from a diverse sample of patients either in treatment for cancer or post-treatment for cancer, we examine inter-domain and cross-domain correlations among the core domains of the Patient-Reported Outcomes Measurement Information System Sexual Function and Satisfaction measures (PROMIS® SexFS) and the corresponding domains from conceptually-similar measures of sexual function, the International Index of Erectile Function and the Female Sexual Function Index. Findings Men (N=389) and women (N=430) were recruited from a tumor registry, oncology clinics, and an internet panel. The PROMIS SexFS, International Index of Erectile Function, and Female Sexual Function Index were used to collect participants’ self-reported sexual function. The domains shared among the measures include desire/interest in sexual activity, lubrication and vaginal discomfort/pain (women), erectile function (men), orgasm, and satisfaction. We examined correlations among different domains within the same instrument (discriminant validity) and correlations among similar domains measured by different instruments (convergent validity). Correlations demonstrating discriminant validity ranged from 0.38 to 0.73 for men and 0.48 to 0.74 for women, while correlations demonstrating convergent validity ranged from 0.62 to 0.83 for men and 0.71 to 0.92 for women. As expected, correlations demonstrating convergent validity were higher than correlations demonstrating discriminant validity, with one exception (orgasm for men). Conclusions Construct validity was supported by convergent and discriminant validity in a diverse sample of patients with cancer. For patients with cancer who may or may not have sexual dysfunction, the PROMIS SexFS measures provide a comprehensive assessment of key domains of sexual function and satisfaction. PMID:23497200

Protein subcellular location pattern classification in cellular images using latent discriminative models.

PubMed

Li, Jieyue; Xiong, Liang; Schneider, Jeff; Murphy, Robert F

2012-06-15

Knowledge of the subcellular location of a protein is crucial for understanding its functions. The subcellular pattern of a protein is typically represented as the set of cellular components in which it is located, and an important task is to determine this set from microscope images. In this article, we address this classification problem using confocal immunofluorescence images from the Human Protein Atlas (HPA) project. The HPA contains images of cells stained for many proteins; each is also stained for three reference components, but there are many other components that are invisible. Given one such cell, the task is to classify the pattern type of the stained protein. We first randomly select local image regions within the cells, and then extract various carefully designed features from these regions. This region-based approach enables us to explicitly study the relationship between proteins and different cell components, as well as the interactions between these components. To achieve these two goals, we propose two discriminative models that extend logistic regression with structured latent variables. The first model allows the same protein pattern class to be expressed differently according to the underlying components in different regions. The second model further captures the spatial dependencies between the components within the same cell so that we can better infer these components. To learn these models, we propose a fast approximate algorithm for inference, and then use gradient-based methods to maximize the data likelihood. In the experiments, we show that the proposed models help improve the classification accuracies on synthetic data and real cellular images. The best overall accuracy we report in this article for classifying 942 proteins into 13 classes of patterns is about 84.6%, which to our knowledge is the best so far. In addition, the dependencies learned are consistent with prior knowledge of cell organization. http://murphylab.web.cmu.edu/software/.

Germ cell transplantation in an azoospermic Klinefelter bull.

PubMed

Joerg, Hannes; Janett, Fredi; Schlatt, Stefan; Mueller, Simone; Graphodatskaya, Daria; Suwattana, Duangsmorn; Asai, Mika; Stranzinger, Gerald

2003-12-01

Germ cell transplantation is a technique that transfers donor testicular cells into recipient testes. A population of germ cells can colonize the recipient testis, initiate spermatogenesis, and produce sperm capable of fertilization. In the present study, a nonmosaic Klinefelter bull was used as a germ cell recipient. The donor cell suspension was introduced into the rete testis using ultrasound-guided puncture. A pulsatile administration of GnRH was performed to stimulate spermatogenesis. The molecular approach to detect donor cells was done by a quantitative polymerase chain reaction with allele discrimination based on a genetic mutation between donor and recipient. Therefore, a known genetic mutation, associated with coat-color phenotype, was used to calculate the ratio of donor to recipient cells in the biopsy specimens and ejaculates for 10 mo. After slaughtering, meiotic preparations were performed. The injected germ cells did not undergo spermatogenesis. Six months after germ cell transplantation, the donor cells were rejected, which indicates that the donor cells could not incorporate in the testis. The hormone stimulation showed that the testosterone-producing Leydig cells were functionally intact. Despite subfertility therapy, neither the recipient nor the donor cells underwent spermatogenesis. Therefore, nonmosaic Klinefelter bulls are not suitable as germ cell recipients. Future germ cell recipients in cattle could be mosaic Klinefelters, interspecies hybrids, bulls with Sertoli cell-only syndrome, or bulls with disrupted germ cell migration caused by RNA interference.

SU-F-R-39: Effects of Radiation Dose Reduction On Renal Cell Carcinoma Discrimination Using Multi-Phasic CT Imaging

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

Wahi-Anwar, M; Young, S; Lo, P

Purpose: A method to discriminate different types of renal cell carcinoma (RCC) was developed using attenuation values observed in multiphasic contrast-enhanced CT. This work evaluates the sensitivity of this RCC discrimination task at different CT radiation dose levels. Methods: We selected 5 cases of kidney lesion patients who had undergone four-phase CT scans covering the abdomen to the lilac crest. Through an IRB-approved study, the scans were conducted on 64-slice CT scanners (Definition AS/Definition Flash, Siemens Healthcare) using automatic tube-current modulation (TCM). The protocol included an initial baseline unenhanced scan, followed by three post-contrast injection phases. CTDIvol (32 cm phantom)more » measured between 9 to 35 mGy for any given phase. As a preliminary study, we limited the scope to the cortico-medullary phase—shown previously to be the most discriminative phase. A previously validated method was used to simulate a reduced dose acquisition via adding noise to raw CT sinogram data, emulating corresponding images at simulated doses of 50%, 25%, and 10%. To discriminate the lesion subtype, ROIs were placed in the most enhancing region of the lesion. The mean HU value of an ROI was extracted and used to discriminate to the worst-case RCC subtype, ranked in the order of clear cell, papillary, chromophobe and the benign oncocytoma. Results: Two patients exhibited a change of worst case RCC subtype between original and simulated scans, at 25% and 10% doses. In one case, the worst-case RCC subtype changed from oncocytoma to chromophobe at 10% and 25% doses, while the other case changed from oncocytoma to clear cell at 10% dose. Conclusion: Based on preliminary results from an initial cohort of 5 patients, worst-case RCC subtypes remained constant at all simulated dose levels except for 2 patients. Further study conducted on more patients will be needed to confirm our findings. Institutional research agreement, Siemens Healthcare; Past recipient, research grant support, Siemens Healthcare; Consultant, Toshiba America Medical Systems; Consultant, Samsung Electronics; NIH Grant Support from: U01 CA181156.« less

Factors influencing the turnover and net isotopic discrimination of hydrogen isotopes in proteinaceous tissue: experimental results using Japanese quail.

PubMed

Storm-Suke, Andrea; Norris, D Ryan; Wassenaar, Leonard I; Chin, Eunice; Nol, Erica

2012-01-01

Stable hydrogen isotopes (δ(2)H) are commonly used in studies of animal movement. Tissue that is metabolically inactive after growth (e.g., feathers) provides spatial or dietary information that reflects only the period of tissue growth, whereas tissues that are metabolically active (e.g., red blood cells) provide a moving window of forensic information. However, using δ(2)H for studies of animal movement relies on the assumption that tissue δ(2)H values reflect dietary δ(2)H values, plus or minus a net diet-tissue discrimination value, and that the turnover rate is known for metabolically active tissue. The metabolic rate of an animal may influence both diet-tissue discrimination values and isotopic tissue turnover rate, but this hypothesis has not been tested experimentally. To examine the metabolic hypothesis, an experimental group of 12 male and 15 female captive Japanese quail (Coturnix japonica) was housed at 8.9°C for 90 d to elevate their metabolic rates (mL CO(2) min(-1)), and a control group of 12 male and 13 female quail was housed at room temperature during the same period. For both experimental and control birds, diet-tissue discrimination values were estimated for red blood cells and feathers. To determine turnover rate, experimental and control birds were switched from a (2)H-enriched diet to a (2)H-depleted diet, with red blood cells sampled before and after diet switch. Metabolic rate did not influence red blood cell hydrogen isotope turnover rate (η(2)(p) = 0.24)) or diet-feather isotope discrimination values (η(2)(p) = 0.86). Diet-feather hydrogen isotopic discrimination had a significant sex plus treatment interaction effect; female feathers were depleted in (2)H relative to food regardless of treatment, whereas male feathers were enriched in (2)H. The effect of sex suggested that experimental studies should examine whether coeval males and females differ in blood δ(2)H levels during certain periods of the annual cycle.

Finding genes discriminating smokers from non-smokers by applying a growing self-organizing clustering method to large airway epithelium cell microarray data.

PubMed

Shahdoust, Maryam; Hajizadeh, Ebrahim; Mozdarani, Hossein; Chehrei, Ali

2013-01-01

Cigarette smoking is the major risk factor for development of lung cancer. Identification of effects of tobacco on airway gene expression may provide insight into the causes. This research aimed to compare gene expression of large airway epithelium cells in normal smokers (n=13) and non-smokers (n=9) in order to find genes which discriminate the two groups and assess cigarette smoking effects on large airway epithelium cells. Genes discriminating smokers from non-smokers were identified by applying a neural network clustering method, growing self-organizing maps (GSOM), to microarray data according to class discrimination scores. An index was computed based on differentiation between each mean of gene expression in the two groups. This clustering approach provided the possibility of comparing thousands of genes simultaneously. The applied approach compared the mean of 7,129 genes in smokers and non-smokers simultaneously and classified the genes of large airway epithelium cells which had differently expressed in smokers comparing with non-smokers. Seven genes were identified which had the highest different expression in smokers compared with the non-smokers group: NQO1, H19, ALDH3A1, AKR1C1, ABHD2, GPX2 and ADH7. Most (NQO1, ALDH3A1, AKR1C1, H19 and GPX2) are known to be clinically notable in lung cancer studies. Furthermore, statistical discriminate analysis showed that these genes could classify samples in smokers and non-smokers correctly with 100% accuracy. With the performed GSOM map, other nodes with high average discriminate scores included genes with alterations strongly related to the lung cancer such as AKR1C3, CYP1B1, UCHL1 and AKR1B10. This clustering by comparing expression of thousands of genes at the same time revealed alteration in normal smokers. Most of the identified genes were strongly relevant to lung cancer in the existing literature. The genes may be utilized to identify smokers with increased risk for lung cancer. A large sample study is now recommended to determine relations between the genes ABHD2 and ADH7 and smoking.

Discriminant analysis of functional optical topography for schizophrenia diagnosis

NASA Astrophysics Data System (ADS)

Chuang, Ching-Cheng; Nakagome, Kazuyuki; Pu, Shenghong; Lan, Tsuo-Hung; Lee, Chia-Yen; Sun, Chia-Wei

2014-01-01

Abnormal prefrontal function plays a central role in the cognition deficits of schizophrenic patients; however, the character of the relationship between discriminant analysis and prefrontal activation remains undetermined. Recently, evidence of low prefrontal cortex (PFC) activation in individuals with schizophrenia has also been found during verbal fluency tests (VFT) and other cognitive tests with several neuroimaging methods. The purpose of this study is to assess the hemodynamic changes of the PFC and discriminant analysis between schizophrenia patients and healthy controls during VFT task by utilizing functional optical topography. A total of 99 subjects including 53 schizophrenic patients and 46 age- and gender-matched healthy controls were studied. The results showed that the healthy group had larger activation in the right and left PFC than in the middle PFC. Besides, the schizophrenic group showed weaker task performance and lower activation in the whole PFC than the healthy group. The result of the discriminant analysis showed a significant difference with P value <0.001 in six channels (CH 23, 29, 31, 40, 42, 52) between the schizophrenic and healthy groups. Finally, 68.69% and 71.72% of subjects are correctly classified as being schizophrenic or healthy with all 52 channels and six significantly different channels, respectively. Our findings suggest that the left PFC can be a feature region for discriminant analysis of schizophrenic diagnosis.

Comparative evaluation of the oral tactile function by means of teeth or implant-supported prostheses.

PubMed

Jacobs, R; van Steenberghe, D

1991-01-01

To clarify more of the tactile function of oral implants, both an interocclusal thickness detection and discrimination task were carried out in 4 different test conditions on 37 patients: t (tooth)/t, i (implant)/t, i/i and d (denture)/o (overdenture supported by implants). For the interocclusal detection of steel foils, the 50% detection threshold level (RL) in the 4 conditions was 20, 48, 64 and 108 microns, respectively, which indicates significant differences. The ability to discriminate interdental thickness differences was tested with a 0.2 and 1.0 mm standard. It was evaluated as the 75% discrimination level (DL). In the 0.2 mm discrimination task, corresponding DL-values for the t/t, i/t, i/i and d/o condition were 25, 55, 66 and 134 microns, whereas the 1.0 mm standard gave values of 193, 293, 336 and 348 microns, respectively. All results differed significantly from each other (p less than 0.05) except for the i/i-d/o comparison of the 1.0 mm discrimination task where the difference was negligible. The present findings indicate that the tactile sensibility of implants is reduced with regard to natural teeth. Remaining receptors of the peri-implant tissues might play a compensatory role in the decreased exteroceptive function.

"More than skin deep": stress neurobiology and mental health consequences of racial discrimination.

PubMed

Berger, Maximus; Sarnyai, Zoltán

2015-01-01

Ethnic minority groups across the world face a complex set of adverse social and psychological challenges linked to their minority status, often involving racial discrimination. Racial discrimination is increasingly recognized as an important contributing factor to health disparities among non-dominant ethnic minorities. A growing body of literature has recognized these health disparities and has investigated the relationship between racial discrimination and poor health outcomes. Chronically elevated cortisol levels and a dysregulated hypothalamic-pituitary-adrenal (HPA) axis appear to mediate effects of racial discrimination on allostatic load and disease. Racial discrimination seems to converge on the anterior cingulate cortex (ACC) and may impair the function of the prefrontal cortex (PFC), hence showing substantial similarities to chronic social stress. This review provides a summary of recent literature on hormonal and neural effects of racial discrimination and a synthesis of potential neurobiological pathways by which discrimination affects mental health.

EXTRACTING PRINCIPLE COMPONENTS FOR DISCRIMINANT ANALYSIS OF FMRI IMAGES

PubMed Central

Liu, Jingyu; Xu, Lai; Caprihan, Arvind; Calhoun, Vince D.

2009-01-01

This paper presents an approach for selecting optimal components for discriminant analysis. Such an approach is useful when further detailed analyses for discrimination or characterization requires dimensionality reduction. Our approach can accommodate a categorical variable such as diagnosis (e.g. schizophrenic patient or healthy control), or a continuous variable like severity of the disorder. This information is utilized as a reference for measuring a component’s discriminant power after principle component decomposition. After sorting each component according to its discriminant power, we extract the best components for discriminant analysis. An application of our reference selection approach is shown using a functional magnetic resonance imaging data set in which the sample size is much less than the dimensionality. The results show that the reference selection approach provides an improved discriminant component set as compared to other approaches. Our approach is general and provides a solid foundation for further discrimination and classification studies. PMID:20582334

EXTRACTING PRINCIPLE COMPONENTS FOR DISCRIMINANT ANALYSIS OF FMRI IMAGES.

PubMed

Liu, Jingyu; Xu, Lai; Caprihan, Arvind; Calhoun, Vince D

2008-05-12

This paper presents an approach for selecting optimal components for discriminant analysis. Such an approach is useful when further detailed analyses for discrimination or characterization requires dimensionality reduction. Our approach can accommodate a categorical variable such as diagnosis (e.g. schizophrenic patient or healthy control), or a continuous variable like severity of the disorder. This information is utilized as a reference for measuring a component's discriminant power after principle component decomposition. After sorting each component according to its discriminant power, we extract the best components for discriminant analysis. An application of our reference selection approach is shown using a functional magnetic resonance imaging data set in which the sample size is much less than the dimensionality. The results show that the reference selection approach provides an improved discriminant component set as compared to other approaches. Our approach is general and provides a solid foundation for further discrimination and classification studies.

Discrimination among populations of sockeye salmon fry with Fourier analysis of otolith banding patterns formed during incubation

USGS Publications Warehouse

Finn, James E.; Burger, Carl V.; Holland-Bartels, Leslie E.

1997-01-01

We used otolith banding patterns formed during incubation to discriminate among hatchery- and wild-incubated fry of sockeye salmon Oncorhynchus nerka from Tustumena Lake, Alaska. Fourier analysis of otolith luminance profiles was used to describe banding patterns: the amplitudes of individual Fourier harmonics were discriminant variables. Correct classification of otoliths to either hatchery or wild origin was 83.1% (cross-validation) and 72.7% (test data) with the use of quadratic discriminant function analysts on 10 Fourier amplitudes. Overall classification rates among the six test groups (one hatchery and five wild groups) were 46.5% (cross-validation) and 39.3% (test data) with the use of linear discriminant function analysis on 16 Fourier amplitudes. Although classification rates for wild-incubated fry from any one site never exceeded 67% (cross-validation) or 60% (test data), location-specific information was evident for all groups because the probability of classifying an individual to its true incubation location was significantly greater than chance. Results indicate phenotypic differences in otolith microstructure among incubation sites separated by less than 10 km. Analysis of otolith luminance profiles is a potentially useful technique for discriminating among and between various populations of hatchery and wild fish.

Comparing success levels of different neural network structures in extracting discriminative information from the response patterns of a temperature-modulated resistive gas sensor

NASA Astrophysics Data System (ADS)

Hosseini-Golgoo, S. M.; Bozorgi, H.; Saberkari, A.

2015-06-01

Performances of three neural networks, consisting of a multi-layer perceptron, a radial basis function, and a neuro-fuzzy network with local linear model tree training algorithm, in modeling and extracting discriminative features from the response patterns of a temperature-modulated resistive gas sensor are quantitatively compared. For response pattern recording, a voltage staircase containing five steps each with a 20 s plateau is applied to the micro-heater of the sensor, when 12 different target gases, each at 11 concentration levels, are present. In each test, the hidden layer neuron weights are taken as the discriminatory feature vector of the target gas. These vectors are then mapped to a 3D feature space using linear discriminant analysis. The discriminative information content of the feature vectors are determined by the calculation of the Fisher’s discriminant ratio, affording quantitative comparison among the success rates achieved by the different neural network structures. The results demonstrate a superior discrimination ratio for features extracted from local linear neuro-fuzzy and radial-basis-function networks with recognition rates of 96.27% and 90.74%, respectively.

Structured Kernel Dictionary Learning with Correlation Constraint for Object Recognition.

PubMed

Wang, Zhengjue; Wang, Yinghua; Liu, Hongwei; Zhang, Hao

2017-06-21

In this paper, we propose a new discriminative non-linear dictionary learning approach, called correlation constrained structured kernel KSVD, for object recognition. The objective function for dictionary learning contains a reconstructive term and a discriminative term. In the reconstructive term, signals are implicitly non-linearly mapped into a space, where a structured kernel dictionary, each sub-dictionary of which lies in the span of the mapped signals from the corresponding class, is established. In the discriminative term, by analyzing the classification mechanism, the correlation constraint is proposed in kernel form, constraining the correlations between different discriminative codes, and restricting the coefficient vectors to be transformed into a feature space, where the features are highly correlated inner-class and nearly independent between-classes. The objective function is optimized by the proposed structured kernel KSVD. During the classification stage, the specific form of the discriminative feature is needless to be known, while the inner product of the discriminative feature with kernel matrix embedded is available, and is suitable for a linear SVM classifier. Experimental results demonstrate that the proposed approach outperforms many state-of-the-art dictionary learning approaches for face, scene and synthetic aperture radar (SAR) vehicle target recognition.

Discriminant function analysis as tool for subsurface geologist

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

Chesser, K.

1987-05-01

Sedimentary structures such as cross-bedding control porosity, permeability, and other petrophysical properties in sandstone reservoirs. Understanding the distribution of such structures in the subsurface not only aids in the prediction of reservoir properties but also provides information about depositional environments. Discriminant function analysis (DFA) is a simple yet powerful method incorporating petrophysical data from wireline logs, core analyses, or other sources into groups that have been previously defined through direct observation of sedimentary structures in cores. Once data have been classified into meaningful groups, the geologist can predict the distribution of specific sedimentary structures or important reservoir properties in areasmore » where cores are unavailable. DFA is efficient. Given several variables, DFA will choose the best combination to discriminate among groups. The initial classification function can be computed from relatively few observations, and additional data may be included as necessary. Furthermore, DFA provides quantitative goodness-of-fit estimates for each observation. Such estimates can be used as mapping parameters or to assess risk in petroleum ventures. Petrophysical data from the Skinner sandstone of Strauss field in southeastern Kansas tested the ability of DFA to discriminate between cross-bedded and ripple-bedded sandstones. Petroleum production in Strauss field is largely restricted to the more permeable cross-bedded sandstones. DFA based on permeability correctly placed 80% of samples into cross-bedded or ripple-bedded groups. Addition of formation factor to the discriminant function increased correct classifications to 83% - a small but statistically significant gain.« less

RNA recognition by a human antibody against brain cytoplasmic 200 RNA

PubMed Central

Jung, Euihan; Lee, Jungmin; Hong, Hyo Jeong; Park, Insoo; Lee, Younghoon

2014-01-01

Diverse functional RNAs participate in a wide range of cellular processes. The RNA structure is critical for function, either on its own or as a complex form with proteins and other ligands. Therefore, analysis of the RNA conformation in cells is essential for understanding their functional mechanisms. However, no appropriate methods have been established as yet. Here, we developed an efficient strategy for panning and affinity maturation of anti-RNA human monoclonal antibodies from a naïve antigen binding fragment (Fab) combinatorial phage library. Brain cytoplasmic 200 (BC200) RNA, which is also highly expressed in some tumors, was used as an RNA antigen. We identified MabBC200-A3 as the optimal binding antibody. Mutagenesis and SELEX experiments showed that the antibody recognized a domain of BC200 in a structure- and sequence-dependent manner. Various breast cancer cell lines were further examined for BC200 RNA expression using conventional hybridization and immunoanalysis with MabBC200-A3 to see whether the antibody specifically recognizes BC200 RNA among the total purified RNAs. The amounts of antibody-recognizable BC200 RNA were consistent with hybridization signals among the cell lines. Furthermore, the antibody was able to discriminate BC200 RNA from other RNAs, supporting the utility of this antibody as a specific RNA structure-recognizing probe. Intriguingly, however, when permeabilized cells were subjected to immunoanalysis instead of purified total RNA, the amount of antibody-recognizable RNA was not correlated with the cellular level of BC200 RNA, indicating that BC200 RNA exists as two distinct forms (antibody-recognizable and nonrecognizable) in breast cancer cells and that their distribution depends on the cell type. Our results clearly demonstrate that anti-RNA antibodies provide an effective novel tool for detecting and analyzing RNA conformation. PMID:24759090

Dissociable contributions of the orbitofrontal and infralimbic cortex to pavlovian autoshaping and discrimination reversal learning: further evidence for the functional heterogeneity of the rodent frontal cortex.

PubMed

Chudasama, Y; Robbins, Trevor W

2003-09-24

To examine possible heterogeneity of function within the ventral regions of the rodent frontal cortex, the present study compared the effects of excitotoxic lesions of the orbitofrontal cortex (OFC) and the infralimbic cortex (ILC) on pavlovian autoshaping and discrimination reversal learning. During the pavlovian autoshaping task, in which rats learn to approach a stimulus predictive of reward [conditional stimulus (CS+)], only the OFC group failed to acquire discriminated approach but was unimpaired when preoperatively trained. In the visual discrimination learning and reversal task, rats were initially required to discriminate a stimulus positively associated with reward. There was no effect of either OFC or ILC lesions on discrimination learning. When the stimulus-reward contingencies were reversed, both groups of animals committed more errors, but only the OFC-lesioned animals were unable to suppress the previously rewarded stimulus-reward association, committing more "stimulus perseverative" errors. In contrast, the ILC group showed a pattern of errors that was more attributable to "learning" than perseveration. These findings suggest two types of dissociation between the effects of OFC and ILC lesions: (1) OFC lesions impaired the learning processes implicated in pavlovian autoshaping but not instrumental simultaneous discrimination learning, whereas ILC lesions were unimpaired at autoshaping and their reversal learning deficit did not reflect perseveration, and (2) OFC lesions induced perseverative responding in reversal learning but did not disinhibit responses to pavlovian CS-. In contrast, the ILC lesion had no effect on response inhibitory control in either of these settings. The findings are discussed in the context of dissociable executive functions in ventral sectors of the rat prefrontal cortex.

Investigating the Predictive Value of Functional MRI to Appetitive and Aversive Stimuli: A Pattern Classification Approach.

PubMed

McCabe, Ciara; Rocha-Rego, Vanessa

2016-01-01

Dysfunctional neural responses to appetitive and aversive stimuli have been investigated as possible biomarkers for psychiatric disorders. However it is not clear to what degree these are separate processes across the brain or in fact overlapping systems. To help clarify this issue we used Gaussian process classifier (GPC) analysis to examine appetitive and aversive processing in the brain. 25 healthy controls underwent functional MRI whilst seeing pictures and receiving tastes of pleasant and unpleasant food. We applied GPCs to discriminate between the appetitive and aversive sights and tastes using functional activity patterns. The diagnostic accuracy of the GPC for the accuracy to discriminate appetitive taste from neutral condition was 86.5% (specificity = 81%, sensitivity = 92%, p = 0.001). If a participant experienced neutral taste stimuli the probability of correct classification was 92. The accuracy to discriminate aversive from neutral taste stimuli was 82.5% (specificity = 73%, sensitivity = 92%, p = 0.001) and appetitive from aversive taste stimuli was 73% (specificity = 77%, sensitivity = 69%, p = 0.001). In the sight modality, the accuracy to discriminate appetitive from neutral condition was 88.5% (specificity = 85%, sensitivity = 92%, p = 0.001), to discriminate aversive from neutral sight stimuli was 92% (specificity = 92%, sensitivity = 92%, p = 0.001), and to discriminate aversive from appetitive sight stimuli was 63.5% (specificity = 73%, sensitivity = 54%, p = 0.009). Our results demonstrate the predictive value of neurofunctional data in discriminating emotional and neutral networks of activity in the healthy human brain. It would be of interest to use pattern recognition techniques and fMRI to examine network dysfunction in the processing of appetitive, aversive and neutral stimuli in psychiatric disorders. Especially where problems with reward and punishment processing have been implicated in the pathophysiology of the disorder.

Paradox of pattern separation and adult neurogenesis: A dual role for new neurons balancing memory resolution and robustness.

PubMed

Johnston, Stephen T; Shtrahman, Matthew; Parylak, Sarah; Gonçalves, J Tiago; Gage, Fred H

2016-03-01

Hippocampal adult neurogenesis is thought to subserve pattern separation, the process by which similar patterns of neuronal inputs are transformed into distinct neuronal representations, permitting the discrimination of highly similar stimuli in hippocampus-dependent tasks. However, the mechanism by which immature adult-born dentate granule neurons cells (abDGCs) perform this function remains unknown. Two theories of abDGC function, one by which abDGCs modulate and sparsify activity in the dentate gyrus and one by which abDGCs act as autonomous coding units, are generally suggested to be mutually exclusive. This review suggests that these two mechanisms work in tandem to dynamically regulate memory resolution while avoiding memory interference and maintaining memory robustness. Copyright © 2015 Elsevier Inc. All rights reserved.

Perceptual consequences of disrupted auditory nerve activity.

PubMed

Zeng, Fan-Gang; Kong, Ying-Yee; Michalewski, Henry J; Starr, Arnold

2005-06-01

Perceptual consequences of disrupted auditory nerve activity were systematically studied in 21 subjects who had been clinically diagnosed with auditory neuropathy (AN), a recently defined disorder characterized by normal outer hair cell function but disrupted auditory nerve function. Neurological and electrophysical evidence suggests that disrupted auditory nerve activity is due to desynchronized or reduced neural activity or both. Psychophysical measures showed that the disrupted neural activity has minimal effects on intensity-related perception, such as loudness discrimination, pitch discrimination at high frequencies, and sound localization using interaural level differences. In contrast, the disrupted neural activity significantly impairs timing related perception, such as pitch discrimination at low frequencies, temporal integration, gap detection, temporal modulation detection, backward and forward masking, signal detection in noise, binaural beats, and sound localization using interaural time differences. These perceptual consequences are the opposite of what is typically observed in cochlear-impaired subjects who have impaired intensity perception but relatively normal temporal processing after taking their impaired intensity perception into account. These differences in perceptual consequences between auditory neuropathy and cochlear damage suggest the use of different neural codes in auditory perception: a suboptimal spike count code for intensity processing, a synchronized spike code for temporal processing, and a duplex code for frequency processing. We also proposed two underlying physiological models based on desynchronized and reduced discharge in the auditory nerve to successfully account for the observed neurological and behavioral data. These methods and measures cannot differentiate between these two AN models, but future studies using electric stimulation of the auditory nerve via a cochlear implant might. These results not only show the unique contribution of neural synchrony to sensory perception but also provide guidance for translational research in terms of better diagnosis and management of human communication disorders.

The self and the nonself: immunorecognition and immunologic functions.

PubMed

del Guercio, P

1993-01-01

For almost a century self-nonself discrimination has been considered the driving force of the immune system and the dogma of self-tolerance (horror autotoxicus) the essential issue for understanding protective immunity and pathologic autoreactivity. This classical picture has been recently challenged by the discovery that the immune system is influenced by internal activation (amor autocognitus) and autoreactive clones are both present and activated in healthy individuals. Central to the concepts of reactivity and tolerance, in other terms, to physiology and pathology, is the analysis of structures involved in immunorecognition and as they contribute to the outcome of the immune response. The capacity of the immune system to recognize nonself structures and eventually react to them developed during evolution probably before the generation of clonally distributed antigen receptors. The high level of autoreactivity that characterizes the immune system seems to suggest that immunocompetent cells never learned to ignore the self, but rather that, sometime during evolution, they specialized in the function of self-identification, one of the most basic activities of all living cells. Autoimmune diseases would result from a pathologic deviation of a physiologic function, just as many other diseases do.

Dry-eye screening by using a functional visual acuity measurement system: the Osaka Study.

PubMed

Kaido, Minako; Uchino, Miki; Yokoi, Norihiko; Uchino, Yuichi; Dogru, Murat; Kawashima, Motoko; Komuro, Aoi; Sonomura, Yukiko; Kato, Hiroaki; Kinoshita, Shigeru; Tsubota, Kazuo

2014-05-06

We determined whether functional visual acuity (VA) parameters and a dry eyes (DEs) symptoms questionnaire could predict DEs in a population of visual terminal display (VDT) users. This prospective study included 491 VDT users from the Osaka Study. Subjects with definite DE, diagnosed with the presence of DE symptoms, tear abnormality (Schirmer test ≤ 5 mm or tear breakup time [TBUT] ≤ 5 seconds), and conjunctivocorneal epithelial damage (total staining score of ≥3 points), or probable DE, diagnosed with the presence of two of them, were assigned to a DE group, and the remainder to a non-DE group. Functional VA was assessed, and DE questionnaires were administered. We assessed whether univariate and discriminant analyses could determine to which group a subject belonged. Sensitivity and specificity were assessed. Of 491 subjects, 320 and 171 were assigned to the DE and non-DE groups, respectively. No significant differences were observed between DE and non-DE groups in Schirmer test value and epithelial damage, but TBUT value (3.1 ± 1.5 vs. 5.9 ± 3.0 seconds). The sensitivity and specificity of single test using functional VA parameters were 59% and 49% in functional VA, 60% and 50% in visual maintenance ratio, and 83% and 30% in frequency of blinking, respectively. According to a discriminant analysis using a combination of functional VA parameters and a DE questionnaire, six variables were selected for the discriminant equation, of which area under the curve (AUC) was 0.735. Sensitivity and specificity of diagnoses predicted by the discriminant equation were 85.9% and 45.6%, respectively. The discriminant equation obtained using functional VA measurement combined with a symptoms questionnaire may suggest the possibility for the first step screening of DE with unstable tear film. Since the questionnaire has an overall poor sensitivity and specificity, further amelioration may be necessary for the actual utilization of this screening tool. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.

Dependence on nuclear factor of activated T-cells (NFAT) levels discriminates conventional T cells from Foxp3+ regulatory T cells

PubMed Central

Vaeth, Martin; Schliesser, Ulrike; Müller, Gerd; Reissig, Sonja; Satoh, Kazuki; Tuettenberg, Andrea; Jonuleit, Helmut; Waisman, Ari; Müller, Martin R.; Serfling, Edgar; Sawitzki, Birgit S.; Berberich-Siebelt, Friederike

2012-01-01

Several lines of evidence suggest nuclear factor of activated T-cells (NFAT) to control regulatory T cells: thymus-derived naturally occurring regulatory T cells (nTreg) depend on calcium signals, the Foxp3 gene harbors several NFAT binding sites, and the Foxp3 (Fork head box P3) protein interacts with NFAT. Therefore, we investigated the impact of NFAT on Foxp3 expression. Indeed, the generation of peripherally induced Treg (iTreg) by TGF-β was highly dependent on NFAT expression because the ability of CD4+ T cells to differentiate into iTreg diminished markedly with the number of NFAT family members missing. It can be concluded that the expression of Foxp3 in TGF-β–induced iTreg depends on the threshold value of NFAT rather than on an individual member present. This is specific for iTreg development, because frequency of nTreg remained unaltered in mice lacking NFAT1, NFAT2, or NFAT4 alone or in combination. Different from expectation, however, the function of both nTreg and iTreg was independent on robust NFAT levels, reflected by less nuclear NFAT in nTreg and iTreg. Accordingly, absence of one or two NFAT members did not alter suppressor activity in vitro or during colitis and transplantation in vivo. This scenario emphasizes an inhibition of high NFAT activity as treatment for autoimmune diseases and in transplantation, selectively targeting the proinflammatory conventional T cells, while keeping Treg functional. PMID:22991461

A risk analysis approach for using discriminant functions to manage logging-related landslides on granitic terrain

Treesearch

Raymond M. Rice; Norman H. Pillsbury; Kurt W. Schmidt

1985-01-01

Abstract - A linear discriminant function, developed to predict debris avalanches after clearcut logging on a granitic batholith in northwestern California, was tested on data from two batholiths. The equation was inaccurate in predicting slope stability on one of them. A new equation based on slope, crown cover, and distance from a stream (retained from the original...

Identification of a new gene regulatory circuit involving B cell receptor activated signaling using a combined analysis of experimental, clinical and global gene expression data

PubMed Central

Schrader, Alexandra; Meyer, Katharina; Walther, Neele; Stolz, Ailine; Feist, Maren; Hand, Elisabeth; von Bonin, Frederike; Evers, Maurits; Kohler, Christian; Shirneshan, Katayoon; Vockerodt, Martina; Klapper, Wolfram; Szczepanowski, Monika; Murray, Paul G.; Bastians, Holger; Trümper, Lorenz; Spang, Rainer; Kube, Dieter

2016-01-01

To discover new regulatory pathways in B lymphoma cells, we performed a combined analysis of experimental, clinical and global gene expression data. We identified a specific cluster of genes that was coherently expressed in primary lymphoma samples and suppressed by activation of the B cell receptor (BCR) through αIgM treatment of lymphoma cells in vitro. This gene cluster, which we called BCR.1, includes numerous cell cycle regulators. A reduced expression of BCR.1 genes after BCR activation was observed in different cell lines and also in CD10+ germinal center B cells. We found that BCR activation led to a delayed entry to and progression of mitosis and defects in metaphase. Cytogenetic changes were detected upon long-term αIgM treatment. Furthermore, an inverse correlation of BCR.1 genes with c-Myc co-regulated genes in distinct groups of lymphoma patients was observed. Finally, we showed that the BCR.1 index discriminates activated B cell-like and germinal centre B cell-like diffuse large B cell lymphoma supporting the functional relevance of this new regulatory circuit and the power of guided clustering for biomarker discovery. PMID:27166259

Postnatal Ablation of Synaptic Retinoic Acid Signaling Impairs Cortical Information Processing and Sensory Discrimination in Mice.

PubMed

Park, Esther; Tjia, Michelle; Zuo, Yi; Chen, Lu

2018-06-06

Retinoic acid (RA) and its receptors (RARs) are well established essential transcriptional regulators during embryonic development. Recent findings in cultured neurons identified an independent and critical post-transcriptional role of RA and RARα in the homeostatic regulation of excitatory and inhibitory synaptic transmission in mature neurons. However, the functional relevance of synaptic RA signaling in vivo has not been established. Here, using somatosensory cortex as a model system and the RARα conditional knock-out mouse as a tool, we applied multiple genetic manipulations to delete RARα postnatally in specific populations of cortical neurons, and asked whether synaptic RA signaling observed in cultured neurons is involved in cortical information processing in vivo Indeed, conditional ablation of RARα in mice via a CaMKIIα-Cre or a layer 5-Cre driver line or via somatosensory cortex-specific viral expression of Cre-recombinase impaired whisker-dependent texture discrimination, suggesting a critical requirement of RARα expression in L5 pyramidal neurons of somatosensory cortex for normal tactile sensory processing. Transcranial two-photon imaging revealed a significant increase in dendritic spine elimination on apical dendrites of somatosensory cortical layer 5 pyramidal neurons in these mice. Interestingly, the enhancement of spine elimination is whisker experience-dependent as whisker trimming rescued the spine elimination phenotype. Additionally, experiencing an enriched environment improved texture discrimination in RARα-deficient mice and reduced excessive spine pruning. Thus, RA signaling is essential for normal experience-dependent cortical circuit remodeling and sensory processing. SIGNIFICANCE STATEMENT The importance of synaptic RA signaling has been demonstrated in in vitro studies. However, whether RA signaling mediated by RARα contributes to neural circuit functions in vivo remains largely unknown. In this study, using a RARα conditional knock-out mouse, we performed multiple regional/cell-type-specific manipulation of RARα expression in the postnatal brain, and show that RARα signaling contributes to normal whisker-dependent texture discrimination as well as regulating spine dynamics of apical dendrites from layer (L5) pyramidal neurons in S1. Deletion of RARα in excitatory neurons in the forebrain induces elevated spine elimination and impaired sensory discrimination. Our study provides novel insights into the role of RARα signaling in cortical processing and experience-dependent spine maturation. Copyright © 2018 the authors 0270-6474/18/385277-12$15.00/0.

The impact of racial discrimination and coping strategies on internalizing symptoms in African American youth.

PubMed

Gaylord-Harden, Noni K; Cunningham, Jamila A

2009-04-01

The current study examined the impact of racial discrimination stress on internalizing symptoms and coping strategies in a sample of 268 African American early adolescents (mean age = 12.90; 56% female) from low-income communities. Information about discrimination stress, coping, and internalizing symptoms was obtained via adolescents' self-report. It was predicted that discrimination stress would be positively associated with depression and anxiety, as well as culturally-specific coping. Finally, culturally-relevant coping and mainstream coping were examined as moderators of the association between discrimination stress and internalizing symptoms. Hierarchical regression analyses indicated that discrimination stress was positively associated with depression and anxiety and predicted culturally-relevant coping while controlling for mainstream coping. Communalistic coping moderated the association between discrimination and anxiety, but demonstrated a vulnerability function by increasing anxiety at high levels of discrimination. The results highlight the salience of racial discrimination for African American adolescents and the importance of considering culturally-specific coping behaviors.

Enrichment rescues contextual discrimination deficit associated with immediate shock.

PubMed

Clemenson, Gregory D; Lee, Star W; Deng, Wei; Barrera, Vanessa R; Iwamoto, Kei S; Fanselow, Michael S; Gage, Fred H

2015-03-01

Adult animals continue to modify their behavior throughout life, a process that is highly influenced by past experiences. To shape behavior, specific mechanisms of neural plasticity to learn, remember, and recall information are required. One of the most robust examples of adult plasticity in the brain occurs in the dentate gyrus (DG) of the hippocampus, through the process of adult neurogenesis. Adult neurogenesis is strongly upregulated by external factors such as voluntary wheel running (RUN) and environmental enrichment (EE); however, the functional differences between these two factors remain unclear. Although both manipulations result in increased neurogenesis, RUN dramatically increases the proliferation of newborn cells and EE promotes their survival. We hypothesize that the method by which these newborn neurons are induced influences their functional role. Furthermore, we examine how EE-induced neurons may be primed to encode and recognize features of novel environments due to their previous enrichment experience. Here, we gave mice a challenging contextual fear-conditioning (FC) procedure to tease out the behavioral differences between RUN-induced neurogenesis and EE-induced neurogenesis. Despite the robust increases in neurogenesis seen in the RUN mice, we found that only EE mice were able to discriminate between similar contexts in this task, indicating that EE mice might use a different cognitive strategy when processing contextual information. Furthermore, we showed that this improvement was dependent on EE-induced neurogenesis, suggesting a fundamental functional difference between RUN-induced neurogenesis and EE-induced neurogenesis. © 2014 Wiley Periodicals, Inc.

Enrichment Rescues Contextual Discrimination Deficit Associated With Immediate Shock

PubMed Central

Clemenson, Gregory D.; Lee, Star W.; Deng, Wei; Barrera, Vanessa R.; Iwamoto, Kei S.; Fanselow, Michael S.; Gage, Fred H.

2015-01-01

Adult animals continue to modify their behavior throughout life, a process that is highly influenced by past experiences. To shape behavior, specific mechanisms of neural plasticity to learn, remember, and recall information are required. One of the most robust examples of adult plasticity in the brain occurs in the dentate gyrus (DG) of the hippocampus, through the process of adult neurogenesis. Adult neurogenesis is strongly upregulated by external factors such as voluntary wheel running (RUN) and environmental enrichment (EE); however, the functional differences between these two factors remain unclear. Although both manipulations result in increased neurogenesis, RUN dramatically increases the proliferation of newborn cells and EE promotes their survival. We hypothesize that the method by which these newborn neurons are induced influences their functional role. Furthermore, we examine how EE-induced neurons may be primed to encode and recognize features of novel environments due to their previous enrichment experience. Here, we gave mice a challenging contextual fear-conditioning (FC) procedure to tease out the behavioral differences between RUN-induced neurogenesis and EE-induced neurogenesis. Despite the robust increases in neurogenesis seen in the RUN mice, we found that only EE mice were able to discriminate between similar contexts in this task, indicating that EE mice might use a different cognitive strategy when processing contextual information. Furthermore, we showed that this improvement was dependent on EE-induced neurogenesis, suggesting a fundamental functional difference between RUN-induced neurogenesis and EE-induced neurogenesis. PMID:25330953

H3.Y discriminates between HIRA and DAXX chaperone complexes and reveals unexpected insights into human DAXX-H3.3-H4 binding and deposition requirements

PubMed Central

Zink, Lisa-Maria; Delbarre, Erwan; Eberl, H. Christian; Keilhauer, Eva C.; Bönisch, Clemens; Pünzeler, Sebastian; Bartkuhn, Marek; Collas, Philippe; Mann, Matthias

2017-01-01

Abstract Histone chaperones prevent promiscuous histone interactions before chromatin assembly. They guarantee faithful deposition of canonical histones and functionally specialized histone variants into chromatin in a spatial- and temporally-restricted manner. Here, we identify the binding partners of the primate-specific and H3.3-related histone variant H3.Y using several quantitative mass spectrometry approaches, and biochemical and cell biological assays. We find the HIRA, but not the DAXX/ATRX, complex to recognize H3.Y, explaining its presence in transcriptionally active euchromatic regions. Accordingly, H3.Y nucleosomes are enriched in the transcription-promoting FACT complex and depleted of repressive post-translational histone modifications. H3.Y mutational gain-of-function screens reveal an unexpected combinatorial amino acid sequence requirement for histone H3.3 interaction with DAXX but not HIRA, and for H3.3 recruitment to PML nuclear bodies. We demonstrate the importance and necessity of specific H3.3 core and C-terminal amino acids in discriminating between distinct chaperone complexes. Further, chromatin immunoprecipitation sequencing experiments reveal that in contrast to euchromatic HIRA-dependent deposition sites, human DAXX/ATRX-dependent regions of histone H3 variant incorporation are enriched in heterochromatic H3K9me3 and simple repeat sequences. These data demonstrate that H3.Y's unique amino acids allow a functional distinction between HIRA and DAXX binding and its consequent deposition into open chromatin. PMID:28334823

Supreme Court rules on disability discrimination.

PubMed

Elliott, R

2000-01-01

On 3 May 2000, the Supreme Court of Canada released a unanimous decision involving the interpretation of the term "handicap" in Québec's anti-discrimination legislation in three complaints filed with the province's human rights commission. While none of the cases involved HIV-related discrimination, the Court's strong decision is of definite benefit in protecting and promoting the rights of people with HIV/AIDS, particularly for those living in Québec. The decision recognizes that people are protected against discrimination based on disability even if their condition does not give rise to any functional limitation and the discrimination is based on the perception that they are disabled.

Role of the middle ear muscle apparatus in mechanisms of speech signal discrimination

NASA Technical Reports Server (NTRS)

Moroz, B. S.; Bazarov, V. G.; Sachenko, S. V.

1980-01-01

A method of impedance reflexometry was used to examine 101 students with hearing impairment in order to clarify the interrelation between speech discrimination and the state of the middle ear muscles. Ability to discriminate speech signals depends to some extent on the functional state of intraaural muscles. Speech discrimination was greatly impaired in the absence of stapedial muscle acoustic reflex, in the presence of low thresholds of stimulation and in very small values of reflex amplitude increase. Discrimination was not impeded in positive AR, high values of relative thresholds and normal increase of reflex amplitude in response to speech signals with augmenting intensity.

Neighborhood Discriminant Hashing for Large-Scale Image Retrieval.

PubMed

Tang, Jinhui; Li, Zechao; Wang, Meng; Zhao, Ruizhen

2015-09-01

With the proliferation of large-scale community-contributed images, hashing-based approximate nearest neighbor search in huge databases has aroused considerable interest from the fields of computer vision and multimedia in recent years because of its computational and memory efficiency. In this paper, we propose a novel hashing method named neighborhood discriminant hashing (NDH) (for short) to implement approximate similarity search. Different from the previous work, we propose to learn a discriminant hashing function by exploiting local discriminative information, i.e., the labels of a sample can be inherited from the neighbor samples it selects. The hashing function is expected to be orthogonal to avoid redundancy in the learned hashing bits as much as possible, while an information theoretic regularization is jointly exploited using maximum entropy principle. As a consequence, the learned hashing function is compact and nonredundant among bits, while each bit is highly informative. Extensive experiments are carried out on four publicly available data sets and the comparison results demonstrate the outperforming performance of the proposed NDH method over state-of-the-art hashing techniques.

Predictor of increase in caregiver burden for disabled elderly at home.

PubMed

Okamoto, Kazushi; Harasawa, Yuko

2009-01-01

In order to classify the caregivers at high risk of increase in their burden early, linear discriminant analysis was performed to obtain an effective discriminant model for differentiation of the presence or absence of increase in caregiver burden. The data obtained by self-administered questionnaire from 193 caregivers of frail elderly from January to February of 2005 were used. The discriminant analysis yielded a statistically significant function explaining 35.0% (Rc=0.59; d.f.=6; p=0.0001). The configuration indicated that the psychological predictors of change in caregiver burden with much perceived stress (1.47), high caregiver burden at baseline (1.28), emotional control (0.75), effort to achieve (-0.28), symptomatic depression (0.20) and "ikigai" (purpose in life) (0.18) made statistically significant contributions to the differentiation between no increase and increase in caregiver burden. The discriminant function showed a sensitivity of 86% and specificity of 81%, and successfully classified 83% of the caregivers. The function at baseline is a simple and useful method for screening of an increase in caregiver burden among caregivers for the frail elderly at home.

Four Theorems on the Psychometric Function

PubMed Central

May, Keith A.; Solomon, Joshua A.

2013-01-01

In a 2-alternative forced-choice (2AFC) discrimination task, observers choose which of two stimuli has the higher value. The psychometric function for this task gives the probability of a correct response for a given stimulus difference, . This paper proves four theorems about the psychometric function. Assuming the observer applies a transducer and adds noise, Theorem 1 derives a convenient general expression for the psychometric function. Discrimination data are often fitted with a Weibull function. Theorem 2 proves that the Weibull “slope” parameter, , can be approximated by , where is the of the Weibull function that fits best to the cumulative noise distribution, and depends on the transducer. We derive general expressions for and , from which we derive expressions for specific cases. One case that follows naturally from our general analysis is Pelli's finding that, when , . We also consider two limiting cases. Theorem 3 proves that, as sensitivity improves, 2AFC performance will usually approach that for a linear transducer, whatever the actual transducer; we show that this does not apply at signal levels where the transducer gradient is zero, which explains why it does not apply to contrast detection. Theorem 4 proves that, when the exponent of a power-function transducer approaches zero, 2AFC performance approaches that of a logarithmic transducer. We show that the power-function exponents of 0.4–0.5 fitted to suprathreshold contrast discrimination data are close enough to zero for the fitted psychometric function to be practically indistinguishable from that of a log transducer. Finally, Weibull reflects the shape of the noise distribution, and we used our results to assess the recent claim that internal noise has higher kurtosis than a Gaussian. Our analysis of for contrast discrimination suggests that, if internal noise is stimulus-independent, it has lower kurtosis than a Gaussian. PMID:24124456

Different cognitive functions discriminate gait performance in younger and older women: A pilot study.

PubMed

Gonzales, Joaquin U; James, C Roger; Yang, Hyung Suk; Jensen, Daniel; Atkins, Lee; Thompson, Brennan J; Al-Khalil, Kareem; O'Boyle, Michael

2016-10-01

Cognitive dysfunction is associated with slower gait speed in older women, but whether cognitive function affects gait performance earlier in life has yet to be investigated. Thus, the objective of this study was to test the hypothesis that cognitive function will discriminate gait performance in healthy younger women. Fast-pace and dual-task gait speed were measured in 30 young to middle-aged (30-45y) and 26 older (61-80y) women without mild cognitive impairment. Visuoperceptual ability, working memory, executive function, and learning ability were assessed using neuropsychological tests. Within each age group, women were divided by the median into lower and higher cognitive function groups to compare gait performance. Younger women with higher visuoperceptual ability had faster fast-pace (2.25±0.30 vs. 1.98±0.18m/s, p≤0.01) and dual-task gait speed (2.02±0.27 vs. 1.69±0.25m/s, p≤0.01) than women with lower visuoperceptual ability. The difference in dual-task gait speed remained significant (p=0.02) after adjusting for age, years of education, and other covariates. Dividing younger women based on other cognitive domains showed no difference in gait performance. In contrast, working memory and executive function discriminated dual-task gait speed (p<0.05) in older women after adjusting for age and education. To our knowledge, this is the first study to show that poorer cognitive function even at a relatively young age can negatively impact mobility. Different cognitive functions discriminated gait performance based on age, highlighting a possible influence of aging in the relationship between cognitive function and mobility in women. Copyright © 2016 Elsevier B.V. All rights reserved.

Sparse, decorrelated odor coding in the mushroom body enhances learned odor discrimination.

PubMed

Lin, Andrew C; Bygrave, Alexei M; de Calignon, Alix; Lee, Tzumin; Miesenböck, Gero

2014-04-01

Sparse coding may be a general strategy of neural systems for augmenting memory capacity. In Drosophila melanogaster, sparse odor coding by the Kenyon cells of the mushroom body is thought to generate a large number of precisely addressable locations for the storage of odor-specific memories. However, it remains untested how sparse coding relates to behavioral performance. Here we demonstrate that sparseness is controlled by a negative feedback circuit between Kenyon cells and the GABAergic anterior paired lateral (APL) neuron. Systematic activation and blockade of each leg of this feedback circuit showed that Kenyon cells activated APL and APL inhibited Kenyon cells. Disrupting the Kenyon cell-APL feedback loop decreased the sparseness of Kenyon cell odor responses, increased inter-odor correlations and prevented flies from learning to discriminate similar, but not dissimilar, odors. These results suggest that feedback inhibition suppresses Kenyon cell activity to maintain sparse, decorrelated odor coding and thus the odor specificity of memories.

Neural dynamics of motion processing and speed discrimination.

PubMed

Chey, J; Grossberg, S; Mingolla, E

1998-09-01

A neural network model of visual motion perception and speed discrimination is presented. The model shows how a distributed population code of speed tuning, that realizes a size-speed correlation, can be derived from the simplest mechanisms whereby activations of multiple spatially short-range filters of different size are transformed into speed-turned cell responses. These mechanisms use transient cell responses to moving stimuli, output thresholds that covary with filter size, and competition. These mechanisms are proposed to occur in the V1-->MT cortical processing stream. The model reproduces empirically derived speed discrimination curves and simulates data showing how visual speed perception and discrimination can be affected by stimulus contrast, duration, dot density and spatial frequency. Model motion mechanisms are analogous to mechanisms that have been used to model 3-D form and figure-ground perception. The model forms the front end of a larger motion processing system that has been used to simulate how global motion capture occurs, and how spatial attention is drawn to moving forms. It provides a computational foundation for an emerging neural theory of 3-D form and motion perception.

Measuring Work Functioning: Validity of a Weighted Composite Work Functioning Approach.

PubMed

Boezeman, Edwin J; Sluiter, Judith K; Nieuwenhuijsen, Karen

2015-09-01

To examine the construct validity of a weighted composite work functioning measurement approach. Workers (health-impaired/healthy) (n = 117) completed a composite measure survey that recorded four central work functioning aspects with existing scales: capacity to work, quality of work performance, quantity of work, and recovery from work. Previous derived weights reflecting the relative importance of these aspects of work functioning were used to calculate the composite weighted work functioning score of the workers. Work role functioning, productivity, and quality of life were used for validation. Correlations were calculated and norms applied to examine convergent and divergent construct validity. A t test was conducted and a norm applied to examine discriminative construct validity. Overall the weighted composite work functioning measure demonstrated construct validity. As predicted, the weighted composite score correlated (p < .001) strongly (r > .60) with work role functioning and productivity (convergent construct validity), and moderately (.30 < r < .60) with physical quality of life and less strongly than work role functioning and productivity with mental quality of life (divergent validity). Further, the weighted composite measure detected that health-impaired workers show with a large effect size (Cohen's d > .80) significantly worse work functioning than healthy workers (discriminative validity). The weighted composite work functioning measurement approach takes into account the relative importance of the different work functioning aspects and demonstrated good convergent, fair divergent, and good discriminative construct validity.

Classifying Failing States

DTIC Science & Technology

2007-03-01

state failure, and Discriminant Analysis to classify states as Stable, Borderline, or Failing based on these indicators. Furthermore, each...nation’s discriminant function scores are used to determine their degree of instability. The methodology is applied to 200 countries for which open source...and go for a long walk. Finally, to my wonderful wife, who now knows more about Discriminant Analysis than any Legal Assistant on the planet, thank

Neural correlates of abnormal sensory discrimination in laryngeal dystonia.

PubMed

Termsarasab, Pichet; Ramdhani, Ritesh A; Battistella, Giovanni; Rubien-Thomas, Estee; Choy, Melissa; Farwell, Ian M; Velickovic, Miodrag; Blitzer, Andrew; Frucht, Steven J; Reilly, Richard B; Hutchinson, Michael; Ozelius, Laurie J; Simonyan, Kristina

2016-01-01

Aberrant sensory processing plays a fundamental role in the pathophysiology of dystonia; however, its underpinning neural mechanisms in relation to dystonia phenotype and genotype remain unclear. We examined temporal and spatial discrimination thresholds in patients with isolated laryngeal form of dystonia (LD), who exhibited different clinical phenotypes (adductor vs. abductor forms) and potentially different genotypes (sporadic vs. familial forms). We correlated our behavioral findings with the brain gray matter volume and functional activity during resting and symptomatic speech production. We found that temporal but not spatial discrimination was significantly altered across all forms of LD, with higher frequency of abnormalities seen in familial than sporadic patients. Common neural correlates of abnormal temporal discrimination across all forms were found with structural and functional changes in the middle frontal and primary somatosensory cortices. In addition, patients with familial LD had greater cerebellar involvement in processing of altered temporal discrimination, whereas sporadic LD patients had greater recruitment of the putamen and sensorimotor cortex. Based on the clinical phenotype, adductor form-specific correlations between abnormal discrimination and brain changes were found in the frontal cortex, whereas abductor form-specific correlations were observed in the cerebellum and putamen. Our behavioral and neuroimaging findings outline the relationship of abnormal sensory discrimination with the phenotype and genotype of isolated LD, suggesting the presence of potentially divergent pathophysiological pathways underlying different manifestations of this disorder.

The effect of convection on infrared detection by antennal warm cells in the bloodsucking bug Rhodnius prolixus

PubMed Central

Tichy, Harald

2015-01-01

Previous work revealed that bloodsucking bugs can discriminate between oscillating changes in infrared (IR) radiation and air temperature (T) using two types of warm cells located in peg-in-pit sensilla and tapered hairs (Zopf LM, Lazzari CR, Tichy H. J Neurophysiol 111: 1341–1349, 2014). These two stimuli are encoded and discriminated by the response quotient of the two warm cell types. IR radiation stimulates the warm cell in the peg-in-pit sensillum more strongly than that in the tapered hair. T stimuli evoke the reverse responses; they stimulate the latter more strongly than the former. In nature, IR and T cues are always present with certain radiation intensities and air temperatures, here referred to as background IR radiation and background T. In this article, we found that the response quotient permits the discrimination of IR and T oscillations even in the presence of different backgrounds. We show that the two warm cells respond well to IR oscillations if the background T operates by natural convection but poorly at forced convection, even if the background T is higher than at natural convection. Background IR radiation strongly affects the responses to T oscillations: the discharge rates of both warm cells are higher the higher the power of the IR background. We compared the warm cell responses with the T measured inside small model objects shaped like a cylinder, a cone, or a disc. The experiments indicate that passive thermal effects of the sense organs rather than intrinsic properties of the sensory cells are responsible for the observed results. PMID:25609113

Multiple degree of freedom object recognition using optical relational graph decision nets

NASA Technical Reports Server (NTRS)

Casasent, David P.; Lee, Andrew J.

1988-01-01

Multiple-degree-of-freedom object recognition concerns objects with no stable rest position with all scale, rotation, and aspect distortions possible. It is assumed that the objects are in a fairly benign background, so that feature extractors are usable. In-plane distortion invariance is provided by use of a polar-log coordinate transform feature space, and out-of-plane distortion invariance is provided by linear discriminant function design. Relational graph decision nets are considered for multiple-degree-of-freedom pattern recognition. The design of Fisher (1936) linear discriminant functions and synthetic discriminant function for use at the nodes of binary and multidecision nets is discussed. Case studies are detailed for two-class and multiclass problems. Simulation results demonstrate the robustness of the processors to quantization of the filter coefficients and to noise.

Understanding the cellular and molecular mechanisms of dominant and recessive inheritance in genetics course.

PubMed

Wanjin, Xing; Morigen, Morigen

2015-01-01

In Mendellian genetics, the dominance and recessiveness are used to describe the functional relationship between two alleles of one gene in a heterozygote. The allele which constitutes a phenotypical character over the other is named dominant and the one functionally masked is called recessive. The definitions thereby led to the creation of Mendel's laws on segregation and independent assortment and subsequent classic genetics. The discrimination of dominance and recessiveness originally is a requirement for Mendel's logical reasoning, but now it should be explained by cellular and molecular principles in the modern genetics. To answer the question raised by students of how the dominance and recessiveness are controlled, we reviewed the recent articles and tried to summarize the cellular and molecular basis of dominant and recessive inheritance. Clearly, understanding the essences of dominant and recessive inheritance requires us to know the dissimilarity of the alleles and their products (RNA and/or proteins), and the way of their function in cells. The alleles spatio-temporally play different roles on offering cells, tissues or organs with discernible phenotypes, namely dominant or recessive. Here, we discuss the changes of allele dominance and recessiveness at the cellular and molecular levels based on the variation of gene structure, gene regulation, function and types of gene products, in order to make students understand gene mutation and function more comprehensively and concretely.

Predictive Compensator Optimization for Head Tracking Lag in Virtual Environments

NASA Technical Reports Server (NTRS)

Adelstein, Barnard D.; Jung, Jae Y.; Ellis, Stephen R.

2001-01-01

We examined the perceptual impact of plant noise parameterization for Kalman Filter predictive compensation of time delays intrinsic to head tracked virtual environments (VEs). Subjects were tested in their ability to discriminate between the VE system's minimum latency and conditions in which artificially added latency was then predictively compensated back to the system minimum. Two head tracking predictors were parameterized off-line according to cost functions that minimized prediction errors in (1) rotation, and (2) rotation projected into translational displacement with emphasis on higher frequency human operator noise. These predictors were compared with a parameterization obtained from the VE literature for cost function (1). Results from 12 subjects showed that both parameterization type and amount of compensated latency affected discrimination. Analysis of the head motion used in the parameterizations and the subsequent discriminability results suggest that higher frequency predictor artifacts are contributory cues for discriminating the presence of predictive compensation.

Race, Race-Based Discrimination, and Health Outcomes Among African Americans

PubMed Central

Mays, Vickie M.; Cochran, Susan D.; Barnes, Namdi W.

2014-01-01

Persistent and vexing health disadvantages accrue to African Americans despite decades of work to erase the effects of race discrimination in this country. Participating in these efforts, psychologists and other social scientists have hypothesized that African Americans’ continuing experiences with racism and discrimination may lie at the root of the many well-documented race-based physical health disparities that affect this population. With newly emerging methodologies in both measurement of contextual factors and functional neuroscience, an opportunity now exists to cleave together a comprehensive understanding of the ways in which discrimination has harmful effects on health. In this article, we review emerging work that locates the cause of race-based health disparities in the external effects of the contextual social space on the internal world of brain functioning and physiologic response. These approaches reflect the growing interdisciplinary nature of psychology in general, and the field of race relations in particular. PMID:16953796

Race, race-based discrimination, and health outcomes among African Americans.

PubMed

Mays, Vickie M; Cochran, Susan D; Barnes, Namdi W

2007-01-01

Persistent and vexing health disadvantages accrue to African Americans despite decades of work to erase the effects of race discrimination in this country. Participating in these efforts, psychologists and other social scientists have hypothesized that African Americans' continuing experiences with racism and discrimination may lie at the root of the many well-documented race-based physical health disparities that affect this population. With newly emerging methodologies in both measurement of contextual factors and functional neuroscience, an opportunity now exists to cleave together a comprehensive understanding of the ways in which discrimination has harmful effects on health. In this article, we review emerging work that locates the cause of race-based health disparities in the external effects of the contextual social space on the internal world of brain functioning and physiologic response. These approaches reflect the growing interdisciplinary nature of psychology in general, and the field of race relations in particular.

Risk factors for eating disorders in Greek- and Anglo-Australian adolescent girls.

PubMed

Mildred, H; Paxton, S J; Wertheim, E H

1995-01-01

Past research indicates ethnicity may be related to eating disorder and related risk factors. The present study examines risk factors for eating disorders in 50 Anglo- and 50 Greek-Australian girls (mean age = 13.5 years). The variables assessed included bulimic tendencies, body dissatisfaction, use of extreme weight loss behaviors (EWLBs), self-esteem, depression and family cohesion and adaptability. Cultural eating patterns were also explored. A stepwise discriminant function analysis to examine whether the two groups could be discriminated on these variables was significant and correctly classified 73.9% of the sample, the chief discriminating variables being Pressure to Eat, EWLBs, and Family Adaptability. Univariate analyses indicated differences between the groups on Pressure to Eat, Family Adaptability, and Mother's Shape. Although the groups were discriminable, a number of variables generally associated with eating disorder did not contribute to the function. These data are discussed in terms of cultural assimilation.

Fingerprinting Breast Cancer vs. Normal Mammary Cells by Mass Spectrometric Analysis of Volatiles

NASA Astrophysics Data System (ADS)

He, Jingjing; Sinues, Pablo Martinez-Lozano; Hollmén, Maija; Li, Xue; Detmar, Michael; Zenobi, Renato

2014-06-01

There is increasing interest in the development of noninvasive diagnostic methods for early cancer detection, to improve the survival rate and quality of life of cancer patients. Identification of volatile metabolic compounds may provide an approach for noninvasive early diagnosis of malignant diseases. Here we analyzed the volatile metabolic signature of human breast cancer cell lines versus normal human mammary cells. Volatile compounds in the headspace of conditioned culture medium were directly fingerprinted by secondary electrospray ionization-mass spectrometry. The mass spectra were subsequently treated statistically to identify discriminating features between normal vs. cancerous cell types. We were able to classify different samples by using feature selection followed by principal component analysis (PCA). Additionally, high-resolution mass spectrometry allowed us to propose their chemical structures for some of the most discriminating molecules. We conclude that cancerous cells can release a characteristic odor whose constituents may be used as disease markers.

Applications of Raman micro-spectroscopy to stem cell technology: label-free molecular discrimination and monitoring cell differentiation.

PubMed

Ghita, Adrian; Pascut, Flavius C; Sottile, Virginie; Denning, Chris; Notingher, Ioan

Stem cell therapy is widely acknowledged as a key medical technology of the 21st century which may provide treatments for many currently incurable diseases. These cells have an enormous potential for cell replacement therapies to cure diseases such as Parkinson's disease, diabetes and cardiovascular disorders, as well as in tissue engineering as a reliable cell source for providing grafts to replace and repair diseased tissues. Nevertheless, the progress in this field has been difficult in part because of lack of techniques that can measure non-invasively the molecular properties of cells. Such repeated measurements can be used to evaluate the culture conditions during differentiation, cell quality and phenotype heterogeneity of stem cell progeny. Raman spectroscopy is an optical technique based on inelastic scattering of laser photons by molecular vibrations of cellular molecules and can be used to provide chemical fingerprints of cells or organelles without fixation, lysis or use of labels and other contrast enhancing chemicals. Because differentiated cells are specialized to perform specific functions, these cells produce specific biochemicals that can be detected by Raman micro-spectroscopy. This mini-review paper describes applications of Raman micro-scpectroscopy to measure moleculare properties of stem cells during differentiation in-vitro. The paper focuses on time- and spatially-resolved Raman spectral measurements that allow repeated investigation of live stem cells in-vitro.

Predicting bacteriophage proteins located in host cell with feature selection technique.

PubMed

Ding, Hui; Liang, Zhi-Yong; Guo, Feng-Biao; Huang, Jian; Chen, Wei; Lin, Hao

2016-04-01

A bacteriophage is a virus that can infect a bacterium. The fate of an infected bacterium is determined by the bacteriophage proteins located in the host cell. Thus, reliably identifying bacteriophage proteins located in the host cell is extremely important to understand their functions and discover potential anti-bacterial drugs. Thus, in this paper, a computational method was developed to recognize bacteriophage proteins located in host cells based only on their amino acid sequences. The analysis of variance (ANOVA) combined with incremental feature selection (IFS) was proposed to optimize the feature set. Using a jackknife cross-validation, our method can discriminate between bacteriophage proteins located in a host cell and the bacteriophage proteins not located in a host cell with a maximum overall accuracy of 84.2%, and can further classify bacteriophage proteins located in host cell cytoplasm and in host cell membranes with a maximum overall accuracy of 92.4%. To enhance the value of the practical applications of the method, we built a web server called PHPred (〈http://lin.uestc.edu.cn/server/PHPred〉). We believe that the PHPred will become a powerful tool to study bacteriophage proteins located in host cells and to guide related drug discovery. Copyright © 2016 Elsevier Ltd. All rights reserved.

Synthesis and analysis of discriminators under influence of broadband non-Gaussian noise

NASA Astrophysics Data System (ADS)

Artyushenko, V. M.; Volovach, V. I.

2018-01-01

We considered the problems of the synthesis and analysis of discriminators, when the useful signal is exposed to non-Gaussian additive broadband noise. It is shown that in this case, the discriminator of the tracking meter should contain the nonlinear transformation unit, the characteristics of which are determined by the Fisher information relative to the probability density function of the mixture of non-Gaussian broadband noise and mismatch errors. The parameters of the discriminatory and phase characteristics of the discriminators working under the above conditions are obtained. It is shown that the efficiency of non-linear processing depends on the ratio of power of FM noise to the power of Gaussian noise. The analysis of the information loss of signal transformation caused by the linear section of discriminatory characteristics of the unit of nonlinear transformations of the discriminator is carried out. It is shown that the average slope of the nonlinear transformation characteristic is determined by the Fisher information relative to the probability density function of the mixture of non-Gaussian noise and mismatch errors.

A Derived Transfer of Simple Discrimination and Self-Reported Arousal Functions in Spider Fearful and Non-Spider-Fearful Participants

ERIC Educational Resources Information Center

Smyth, Sinead; Barnes-Holmes, Dermot; Forsyth, John P.

2006-01-01

Two experiments investigated the derived transfer of functions through equivalence relations established using a stimulus pairing observation procedure. In Experiment 1, participants were trained on a simple discrimination (A1+/A2-) and then a stimulus pairing observation procedure was used to establish 4 stimulus pairings (A1-B1, A2-B2, B1-C1,…

determination of sex in south african blacks by discriminant function analysis of mandibular linear dimensions : A preliminary investigation using the zulu local population.

PubMed

Franklin, Daniel; O'Higgins, Paul; Oxnard, Charles E; Dadour, Ian

2006-12-01

The determination of sex is a critical component in forensic anthropological investigation. The literature attests to numerous metrical standards, each utilizing diffetent skeletal elements, for sex determination in South A frican Blacks. Metrical standards are popular because they provide a high degree of expected accuracy and are less error-prone than subjective nonmetric visual techniques. We note, however, that there appears to be no established metric mandible discriminant function standards for sex determination in this population.We report here on a preliminary investigation designed to evaluate whether the mandible is a practical element for sex determination in South African Blacks. The sample analyzed comprises 40 nonpathological Zulu individuals drawn from the R.A. Dart Collection. Ten linear measurements, obtained from mathematically trans-formed three-dimensional landmark data, are analyzed using basic univariate statistics and discriminant function analyses. Seven of the 10 measurements examined are found to be sexually dimorphic; the dimensions of the ramus are most dimorphic. The sex classification accuracy of the discriminant functions ranged from 72.5 to 87.5% for the univariate method, 92.5% for the stepwise method, and 57.5 to 95% for the direct method. We conclude that the mandible is an extremely useful element for sex determination in this population.

Studies of neutron-γ pulse shape discrimination in EJ-309 liquid scintillator using charge integration method

NASA Astrophysics Data System (ADS)

Pawełczak, I. A.; Ouedraogo, S. A.; Glenn, A. M.; Wurtz, R. E.; Nakae, L. F.

2013-05-01

Pulse shape discrimination capability based on the charge integration has been investigated for liquid scintillator EJ-309. The effectiveness of neutron-γ discrimination in 4-in. diameter and 3-in. thick EJ-309 cells coupled with 3-in. photomultiplier tubes has been carefully studied in the laboratory environment and compared to the commonly used EJ-301 liquid scintillator formulation. Influences of distortions in pulse shape caused by 13.7-m long cables necessary for some remote operations have been examined. The parameter space for an effective neutron-γ discrimination for these assays, such as position and width of a gate used for integration of the delayed light, has been explored.

Olfactory abnormalities in Huntington's disease: decreased plasticity in the primary olfactory cortex of R6/1 transgenic mice and reduced olfactory discrimination in patients.

PubMed

Lazic, Stanley E; Goodman, Anna O G; Grote, Helen E; Blakemore, Colin; Morton, A Jennifer; Hannan, Anthony J; van Dellen, Anton; Barker, Roger A

2007-06-02

Reduced neuronal plasticity in the striatum, hippocampus, and neocortex is a common feature of transgenic mouse models of Huntington's disease (HD). Doublecortin (DCX) and polysialylated neural cell adhesion molecule (PSA-NCAM) are associated with structural plasticity in the adult mammalian brain, are markers of newly formed neurons in the dentate gyrus of the adult hippocampus, and are highly expressed in primary olfactory (piriform) cortex. Animal studies have demonstrated that a reduction in plasticity in the piriform cortex is associated with a selective impairment in odour discrimination. Therefore, the number of DCX and PSA-NCAM immunoreactive cells in the piriform cortex were quantified as measures of plasticity in early stage (fifteen week old) R6/1 transgenic HD mice. The transgenic mice had a large reduction in the number of DCX and PSA-NCAM immunoreactive cells in the piriform cortex, similar to that previously reported in the R6/2 mice. We also tested whether odour discrimination, as well as identification and detection, were impaired in HD patients and found that patients (at a similar disease stage as the mice) had an impairment in odour discrimination and identification, but not odour detection. These results suggest that olfactory impairments observed in HD patients may be the result of reduced plasticity in the primary olfactory cortex.

Clustering effects on postprandial insulin secretion and sensitivity in response to meals with different fatty acid compositions.

PubMed

Bermudez, Beatriz; Ortega-Gomez, Almudena; Varela, Lourdes M; Villar, Jose; Abia, Rocio; Muriana, Francisco J G; Lopez, Sergio

2014-07-25

Dietary fatty acids play a role in glucose homeostasis. The aim of this study was to assess the individual relationship between dietary saturated (SFA), monounsaturated (MUFA) and polyunsaturated (PUFA) fatty acids with postprandial β-cell function and insulin sensitivity in subjects with normal and high fasting triglycerides. We assessed postprandial β-cell function (by the insulinogenic index and the ratio of the insulin to glucose areas under the time-concentration curve) and insulin sensitivity (by the oral glucose and the minimal model insulin sensitivity indices) over four nonconsecutive, randomly assigned, high-fat meals containing a panel of SFA (palmitic and stearic acids), MUFA (palmitoleic and oleic acids) and PUFA (linoleic and α-linolenic acids) in 14 subjects with normal and in 14 subjects with high fasting triglycerides. The proportions of each fatty acid in the meals and the values for surrogate measures of postprandial β-cell function and insulin sensitivity were subjected to a Pearson correlation and hierarchical cluster analysis, which revealed two classes of dietary fatty acids for regulating postprandial glucose homeostasis. We successfully discriminated the adverse effects of SFA palmitic acid from the beneficial effects of MUFA oleic acid on postprandial β-cell function (r ≥ 0.84 for SFA palmitic acid and r ≥ -0.71 for MUFA oleic acid; P < 0.05) and insulin sensitivity (r ≥ -0.92 for SFA palmitic acid and r ≥ 0.89 for MUFA oleic acid; P < 0.001) both in subjects with normal and high fasting triglycerides. In conclusion, dietary MUFA oleic acid, in contrast to SFA palmitic acid, favours the tuning towards better postprandial glycaemic control in subjects with normal and high fasting triglycerides.

Extracellular Vesicle Heterogeneity: Subpopulations, Isolation Techniques, and Diverse Functions in Cancer Progression.

PubMed

Willms, Eduard; Cabañas, Carlos; Mäger, Imre; Wood, Matthew J A; Vader, Pieter

2018-01-01

Cells release membrane enclosed nano-sized vesicles termed extracellular vesicles (EVs) that function as mediators of intercellular communication by transferring biological information between cells. Tumor-derived EVs have emerged as important mediators in cancer development and progression, mainly through transfer of their bioactive content which can include oncoproteins, oncogenes, chemokine receptors, as well as soluble factors, transcripts of proteins and miRNAs involved in angiogenesis or inflammation. This transfer has been shown to influence the metastatic behavior of primary tumors. Moreover, tumor-derived EVs have been shown to influence distant cellular niches, establishing favorable microenvironments that support growth of disseminated cancer cells upon their arrival at these pre-metastatic niches. It is generally accepted that cells release a number of major EV populations with distinct biophysical properties and biological functions. Exosomes, microvesicles, and apoptotic bodies are EV populations most widely studied and characterized. They are discriminated based primarily on their intracellular origin. However, increasing evidence suggests that even within these EV populations various subpopulations may exist. This heterogeneity introduces an extra level of complexity in the study of EV biology and function. For example, EV subpopulations could have unique roles in the intricate biological processes underlying cancer biology. Here, we discuss current knowledge regarding the role of subpopulations of EVs in cancer development and progression and highlight the relevance of EV heterogeneity. The position of tetraspanins and integrins therein will be highlighted. Since addressing EV heterogeneity has become essential for the EV field, current and novel techniques for isolating EV subpopulations will also be discussed. Further dissection of EV heterogeneity will advance our understanding of the critical roles of EVs in health and disease.

The natural defense system and the normative self model

PubMed Central

Kourilsky, Philippe

2016-01-01

Infectious agents are not the only agressors, and the immune system is not the sole defender of the organism. In an enlarged perspective, the ‘normative self model’ postulates that a ‘natural defense system’ protects man and other complex organisms against the environmental and internal hazards of life, including infections and cancers. It involves multiple error detection and correction mechanisms that confer robustness to the body at all levels of its organization. According to the model, the self relies on a set of physiological norms, and NONself (meaning : Non Obedient to the Norms of the self) is anything ‘off-norms’. The natural defense system comprises a set of ‘civil defenses’ (to which all cells in organs and tissues contribute), and a ‘professional army ‘, made of a smaller set of mobile cells. Mobile and non mobile cells differ in their tuning abilities. Tuning extends the recognition capabilities of NONself by the mobile cells, which increase their defensive function. To prevent them to drift, which would compromise self/NONself discrimination, the more plastic mobile cells need to periodically refer to the more stable non mobile cells to keep within physiological standards. PMID:27303629

Techniques to improve the direct ex vivo detection of low frequency antigen-specific CD8+ T cells with peptide-major histocompatibility complex class I tetramers

PubMed Central

Chattopadhyay, Pratip K.; Melenhorst, J. Joseph; Ladell, Kristin; Gostick, Emma; Scheinberg, Philip; Barrett, A. John; Wooldridge, Linda; Roederer, Mario; Sewell, Andrew K.; Price, David A.

2008-01-01

The ability to quantify and characterize antigen-specific CD8+ T cells irrespective of functional readouts using fluorochrome-conjugated tetrameric peptide-MHC class I (pMHCI) complexes in conjunction with flow cytometry has transformed our understanding of cellular immune responses over the past decade. In the case of prevalent CD8+ T cell populations that engage cognate pMHCI tetramers with high avidities, direct ex vivo identification and subsequent data interpretation is relatively straightforward. However, the accurate identification of low frequency antigen-specific CD8+ T cell populations can be complicated, especially in situations where TCR-mediated tetramer binding occurs at low avidities. Here, we highlight a few simple techniques that can be employed to improve the visual resolution, and hence the accurate quantification, of tetramer-binding CD8+ T cell populations by flow cytometry. These methodological modifications enhance signal intensity, especially in the case of specific CD8+ T cell populations that bind cognate antigen with low avidity, minimize background noise and enable improved discrimination of true pMHCI tetramer binding events from nonspecific uptake. PMID:18836993

Application of cluster and discriminant analyses to diagnose lithological heterogeneity of the parent material according to its particle-size distribution

NASA Astrophysics Data System (ADS)

Giniyatullin, K. G.; Valeeva, A. A.; Smirnova, E. V.

2017-08-01

Particle-size distribution in soddy-podzolic and light gray forest soils of the Botanical Garden of Kazan Federal University has been studied. The cluster analysis of data on the samples from genetic soil horizons attests to the lithological heterogeneity of the profiles of all the studied soils. It is probable that they are developed from the two-layered sediments with the upper colluvial layer underlain by the alluvial layer. According to the discriminant analysis, the major contribution to the discrimination of colluvial and alluvial layers is that of the fraction >0.25 mm. The results of canonical analysis show that there is only one significant discriminant function that separates alluvial and colluvial sediments on the investigated territory. The discriminant function correlates with the contents of fractions 0.05-0.01, 0.25-0.05, and >0.25 mm. Classification functions making it possible to distinguish between alluvial and colluvial sediments have been calculated. Statistical assessment of particle-size distribution data obtained for the plow horizons on ten plowed fields within the garden indicates that this horizon is formed from colluvial sediments. We conclude that the contents of separate fractions and their ratios cannot be used as a universal criterion of the lithological heterogeneity. However, adequate combination of the cluster and discriminant analyses makes it possible to give a comprehensive assessment of the lithology of soil samples from data on the contents of sand and silt fractions, which considerably increases the information value and reliability of the results.

Neural discriminability in rat lateral extrastriate cortex and deep but not superficial primary visual cortex correlates with shape discriminability.

PubMed

Vermaercke, Ben; Van den Bergh, Gert; Gerich, Florian; Op de Beeck, Hans

2015-01-01

Recent studies have revealed a surprising degree of functional specialization in rodent visual cortex. It is unknown to what degree this functional organization is related to the well-known hierarchical organization of the visual system in primates. We designed a study in rats that targets one of the hallmarks of the hierarchical object vision pathway in primates: selectivity for behaviorally relevant dimensions. We compared behavioral performance in a visual water maze with neural discriminability in five visual cortical areas. We tested behavioral discrimination in two independent batches of six rats using six pairs of shapes used previously to probe shape selectivity in monkey cortex (Lehky and Sereno, 2007). The relative difficulty (error rate) of shape pairs was strongly correlated between the two batches, indicating that some shape pairs were more difficult to discriminate than others. Then, we recorded in naive rats from five visual areas from primary visual cortex (V1) over areas LM, LI, LL, up to lateral occipito-temporal cortex (TO). Shape selectivity in the upper layers of V1, where the information enters cortex, correlated mostly with physical stimulus dissimilarity and not with behavioral performance. In contrast, neural discriminability in lower layers of all areas was strongly correlated with behavioral performance. These findings, in combination with the results from Vermaercke et al. (2014b), suggest that the functional specialization in rodent lateral visual cortex reflects a processing hierarchy resulting in the emergence of complex selectivity that is related to behaviorally relevant stimulus differences.

Drosophila Uri, a PP1α binding protein, is essential for viability, maintenance of DNA integrity and normal transcriptional activity

PubMed Central

Kirchner, Jasmin; Vissi, Emese; Gross, Sascha; Szoor, Balazs; Rudenko, Andrey; Alphey, Luke; White-Cooper, Helen

2008-01-01

Background Protein phosphatase 1 (PP1) is involved in diverse cellular processes, and is targeted to substrates via interaction with many different protein binding partners. PP1 catalytic subunits (PP1c) fall into PP1α and PP1β subfamilies based on sequence analysis, however very few PP1c binding proteins have been demonstrated to discriminate between PP1α and PP1β. Results URI (unconventional prefoldin RPB5 interactor) is a conserved molecular chaperone implicated in a variety of cellular processes, including the transcriptional response to nutrient signalling and maintenance of DNA integrity. We show that Drosophila Uri binds PP1α with much higher affinity than PP1β, and that this ability to discriminate between PP1c forms is conserved to humans. Most Uri is cytoplasmic, however we found some protein associated with active RNAPII on chromatin. We generated a uri loss of function allele, and show that uri is essential for viability in Drosophila. uri mutants have transcriptional defects, reduced cell viability and differentiation in the germline, and accumulate DNA damage in their nuclei. Conclusion Uri is the first PP1α specific binding protein to be described in Drosophila. Uri protein plays a role in transcriptional regulation. Activity of uri is required to maintain DNA integrity and cell survival in normal development. PMID:18412953

Merkel cells and Meissner's corpuscles in human digital skin display Piezo2 immunoreactivity.

PubMed

García-Mesa, Y; García-Piqueras, J; García, B; Feito, J; Cabo, R; Cobo, J; Vega, J A; García-Suárez, O

2017-12-01

The transformation of mechanical energy into electrical signals is the first step in mechanotransduction in the peripheral sensory nervous system and relies on the presence of mechanically gated ion channels within specialized sensory organs called mechanoreceptors. Piezo2 is a vertebrate stretch-gated ion channel necessary for mechanosensitive channels in mammalian cells. Functionally, it is related to light touch, which has been detected in murine cutaneous Merkel cell-neurite complexes, Meissner-like corpuscles and lanceolate nerve endings. To the best of our knowledge, the occurrence of Piezo2 in human cutaneous mechanoreceptors has never been investigated. Here, we used simple and double immunohistochemistry to investigate the occurrence of Piezo2 in human digital glabrous skin. Piezo2 immunoreactivity was detected in approximately 80% of morphologically and immunohistochemically characterized (cytokeratin 20 + , chromogranin A + and synaptophisin + ) Merkel cells. Most of them were in close contact with Piezo2 - nerve fibre profiles. Moreover, the axon, but not the lamellar cells, of Meissner's corpuscles was also Piezo2 + , but other mechanoreceptors, i.e. Pacinian or Ruffini's corpuscles, were devoid of immunoreactivity. Piezo2 was also observed in non-nervous tissue, especially the basal keratinocytes, endothelial cells and sweat glands. The present results demonstrate the occurrence of Piezo2 in cutaneous sensory nerve formations that functionally work as slowly adapting (Merkel cells) and rapidly adapting (Meissner's corpuscles) low-threshold mechanoreceptors and are related to fine and discriminative touch but not to vibration or hard touch. These data offer additional insight into the molecular basis of mechanosensing in humans. © 2017 Anatomical Society.

Protein social behavior makes a stronger signal for partner identification than surface geometry

PubMed Central

Laine, Elodie

2016-01-01

ABSTRACT Cells are interactive living systems where proteins movements, interactions and regulation are substantially free from centralized management. How protein physico‐chemical and geometrical properties determine who interact with whom remains far from fully understood. We show that characterizing how a protein behaves with many potential interactors in a complete cross‐docking study leads to a sharp identification of its cellular/true/native partner(s). We define a sociability index, or S‐index, reflecting whether a protein likes or not to pair with other proteins. Formally, we propose a suitable normalization function that accounts for protein sociability and we combine it with a simple interface‐based (ranking) score to discriminate partners from non‐interactors. We show that sociability is an important factor and that the normalization permits to reach a much higher discriminative power than shape complementarity docking scores. The social effect is also observed with more sophisticated docking algorithms. Docking conformations are evaluated using experimental binding sites. These latter approximate in the best possible way binding sites predictions, which have reached high accuracy in recent years. This makes our analysis helpful for a global understanding of partner identification and for suggesting discriminating strategies. These results contradict previous findings claiming the partner identification problem being solvable solely with geometrical docking. Proteins 2016; 85:137–154. © 2016 Wiley Periodicals, Inc. PMID:27802579

Characteristics of cesium iodide for use as a particle discriminator for high energy cosmic rays

NASA Technical Reports Server (NTRS)

Crannell, C. J.; Kurz, R. J.; Viehmann, W.

1973-01-01

The possible use of CsI to discriminate between high energy cosmic ray electrons and interacting protons has been investigated. The pulse-shape properties as a function of ionization density, temperature, and spectral response are presented for thallium-activated CsI and as a function of ionization density for sodium-activated CsI. The results are based on previously published data and on corroborative measurements from the present work. Experimental results on the response of CsI to electron-induced electromagnetic cascades and to interacting hadrons are described. Bibliographies of publications dealing with the properties of CsI and with pulse-shape discrimination techniques are presented.

A discrimination method for the detection of pneumonia using chest radiograph.

PubMed

Noor, Norliza Mohd; Rijal, Omar Mohd; Yunus, Ashari; Abu-Bakar, S A R

2010-03-01

This paper presents a statistical method for the detection of lobar pneumonia when using digitized chest X-ray films. Each region of interest was represented by a vector of wavelet texture measures which is then multiplied by the orthogonal matrix Q(2). The first two elements of the transformed vectors were shown to have a bivariate normal distribution. Misclassification probabilities were estimated using probability ellipsoids and discriminant functions. The result of this study recommends the detection of pneumonia by constructing probability ellipsoids or discriminant function using maximum energy and maximum column sum energy texture measures where misclassification probabilities were less than 0.15. 2009 Elsevier Ltd. All rights reserved.

Identification of immune cell infiltration in hematoxylin-eosin stained breast cancer samples: texture-based classification of tissue morphologies

NASA Astrophysics Data System (ADS)

Turkki, Riku; Linder, Nina; Kovanen, Panu E.; Pellinen, Teijo; Lundin, Johan

2016-03-01

The characteristics of immune cells in the tumor microenvironment of breast cancer capture clinically important information. Despite the heterogeneity of tumor-infiltrating immune cells, it has been shown that the degree of infiltration assessed by visual evaluation of hematoxylin-eosin (H and E) stained samples has prognostic and possibly predictive value. However, quantification of the infiltration in H and E-stained tissue samples is currently dependent on visual scoring by an expert. Computer vision enables automated characterization of the components of the tumor microenvironment, and texture-based methods have successfully been used to discriminate between different tissue morphologies and cell phenotypes. In this study, we evaluate whether local binary pattern texture features with superpixel segmentation and classification with support vector machine can be utilized to identify immune cell infiltration in H and E-stained breast cancer samples. Guided with the pan-leukocyte CD45 marker, we annotated training and test sets from 20 primary breast cancer samples. In the training set of arbitrary sized image regions (n=1,116) a 3-fold cross-validation resulted in 98% accuracy and an area under the receiver-operating characteristic curve (AUC) of 0.98 to discriminate between immune cell -rich and - poor areas. In the test set (n=204), we achieved an accuracy of 96% and AUC of 0.99 to label cropped tissue regions correctly into immune cell -rich and -poor categories. The obtained results demonstrate strong discrimination between immune cell -rich and -poor tissue morphologies. The proposed method can provide a quantitative measurement of the degree of immune cell infiltration and applied to digitally scanned H and E-stained breast cancer samples for diagnostic purposes.

Speech Discrimination Difficulties in High-Functioning Autism Spectrum Disorder Are Likely Independent of Auditory Hypersensitivity

PubMed Central

Dunlop, William A.; Enticott, Peter G.; Rajan, Ramesh

2016-01-01

Autism Spectrum Disorder (ASD), characterized by impaired communication skills and repetitive behaviors, can also result in differences in sensory perception. Individuals with ASD often perform normally in simple auditory tasks but poorly compared to typically developed (TD) individuals on complex auditory tasks like discriminating speech from complex background noise. A common trait of individuals with ASD is hypersensitivity to auditory stimulation. No studies to our knowledge consider whether hypersensitivity to sounds is related to differences in speech-in-noise discrimination. We provide novel evidence that individuals with high-functioning ASD show poor performance compared to TD individuals in a speech-in-noise discrimination task with an attentionally demanding background noise, but not in a purely energetic noise. Further, we demonstrate in our small sample that speech-hypersensitivity does not appear to predict performance in the speech-in-noise task. The findings support the argument that an attentional deficit, rather than a perceptual deficit, affects the ability of individuals with ASD to discriminate speech from background noise. Finally, we piloted a novel questionnaire that measures difficulty hearing in noisy environments, and sensitivity to non-verbal and verbal sounds. Psychometric analysis using 128 TD participants provided novel evidence for a difference in sensitivity to non-verbal and verbal sounds, and these findings were reinforced by participants with ASD who also completed the questionnaire. The study was limited by a small and high-functioning sample of participants with ASD. Future work could test larger sample sizes and include lower-functioning ASD participants. PMID:27555814

Dimensional feature weighting utilizing multiple kernel learning for single-channel talker location discrimination using the acoustic transfer function.

PubMed

Takashima, Ryoichi; Takiguchi, Tetsuya; Ariki, Yasuo

2013-02-01

This paper presents a method for discriminating the location of the sound source (talker) using only a single microphone. In a previous work, the single-channel approach for discriminating the location of the sound source was discussed, where the acoustic transfer function from a user's position is estimated by using a hidden Markov model of clean speech in the cepstral domain. In this paper, each cepstral dimension of the acoustic transfer function is newly weighted, in order to obtain the cepstral dimensions having information that is useful for classifying the user's position. Then, this paper proposes a feature-weighting method for the cepstral parameter using multiple kernel learning, defining the base kernels for each cepstral dimension of the acoustic transfer function. The user's position is trained and classified by support vector machine. The effectiveness of this method has been confirmed by sound source (talker) localization experiments performed in different room environments.

An on-chip imaging droplet-sorting system: a real-time shape recognition method to screen target cells in droplets with single cell resolution

NASA Astrophysics Data System (ADS)

Girault, Mathias; Kim, Hyonchol; Arakawa, Hisayuki; Matsuura, Kenji; Odaka, Masao; Hattori, Akihiro; Terazono, Hideyuki; Yasuda, Kenji

2017-01-01

A microfluidic on-chip imaging cell sorter has several advantages over conventional cell sorting methods, especially to identify cells with complex morphologies such as clusters. One of the remaining problems is how to efficiently discriminate targets at the species level without labelling. Hence, we developed a label-free microfluidic droplet-sorting system based on image recognition of cells in droplets. To test the applicability of this method, a mixture of two plankton species with different morphologies (Dunaliella tertiolecta and Phaeodactylum tricornutum) were successfully identified and discriminated at a rate of 10 Hz. We also examined the ability to detect the number of objects encapsulated in a droplet. Single cell droplets sorted into collection channels showed 91 ± 4.5% and 90 ± 3.8% accuracy for D. tertiolecta and P. tricornutum, respectively. Because we used image recognition to confirm single cell droplets, we achieved highly accurate single cell sorting. The results indicate that the integrated method of droplet imaging cell sorting can provide a complementary sorting approach capable of isolating single target cells from a mixture of cells with high accuracy without any staining.

An on-chip imaging droplet-sorting system: a real-time shape recognition method to screen target cells in droplets with single cell resolution.

PubMed

Girault, Mathias; Kim, Hyonchol; Arakawa, Hisayuki; Matsuura, Kenji; Odaka, Masao; Hattori, Akihiro; Terazono, Hideyuki; Yasuda, Kenji

2017-01-06

A microfluidic on-chip imaging cell sorter has several advantages over conventional cell sorting methods, especially to identify cells with complex morphologies such as clusters. One of the remaining problems is how to efficiently discriminate targets at the species level without labelling. Hence, we developed a label-free microfluidic droplet-sorting system based on image recognition of cells in droplets. To test the applicability of this method, a mixture of two plankton species with different morphologies (Dunaliella tertiolecta and Phaeodactylum tricornutum) were successfully identified and discriminated at a rate of 10 Hz. We also examined the ability to detect the number of objects encapsulated in a droplet. Single cell droplets sorted into collection channels showed 91 ± 4.5% and 90 ± 3.8% accuracy for D. tertiolecta and P. tricornutum, respectively. Because we used image recognition to confirm single cell droplets, we achieved highly accurate single cell sorting. The results indicate that the integrated method of droplet imaging cell sorting can provide a complementary sorting approach capable of isolating single target cells from a mixture of cells with high accuracy without any staining.

An on-chip imaging droplet-sorting system: a real-time shape recognition method to screen target cells in droplets with single cell resolution

PubMed Central

Girault, Mathias; Kim, Hyonchol; Arakawa, Hisayuki; Matsuura, Kenji; Odaka, Masao; Hattori, Akihiro; Terazono, Hideyuki; Yasuda, Kenji

2017-01-01

A microfluidic on-chip imaging cell sorter has several advantages over conventional cell sorting methods, especially to identify cells with complex morphologies such as clusters. One of the remaining problems is how to efficiently discriminate targets at the species level without labelling. Hence, we developed a label-free microfluidic droplet-sorting system based on image recognition of cells in droplets. To test the applicability of this method, a mixture of two plankton species with different morphologies (Dunaliella tertiolecta and Phaeodactylum tricornutum) were successfully identified and discriminated at a rate of 10 Hz. We also examined the ability to detect the number of objects encapsulated in a droplet. Single cell droplets sorted into collection channels showed 91 ± 4.5% and 90 ± 3.8% accuracy for D. tertiolecta and P. tricornutum, respectively. Because we used image recognition to confirm single cell droplets, we achieved highly accurate single cell sorting. The results indicate that the integrated method of droplet imaging cell sorting can provide a complementary sorting approach capable of isolating single target cells from a mixture of cells with high accuracy without any staining. PMID:28059147

Growth control of the eukaryote cell: a systems biology study in yeast.

PubMed

Castrillo, Juan I; Zeef, Leo A; Hoyle, David C; Zhang, Nianshu; Hayes, Andrew; Gardner, David Cj; Cornell, Michael J; Petty, June; Hakes, Luke; Wardleworth, Leanne; Rash, Bharat; Brown, Marie; Dunn, Warwick B; Broadhurst, David; O'Donoghue, Kerry; Hester, Svenja S; Dunkley, Tom Pj; Hart, Sarah R; Swainston, Neil; Li, Peter; Gaskell, Simon J; Paton, Norman W; Lilley, Kathryn S; Kell, Douglas B; Oliver, Stephen G

2007-01-01

Cell growth underlies many key cellular and developmental processes, yet a limited number of studies have been carried out on cell-growth regulation. Comprehensive studies at the transcriptional, proteomic and metabolic levels under defined controlled conditions are currently lacking. Metabolic control analysis is being exploited in a systems biology study of the eukaryotic cell. Using chemostat culture, we have measured the impact of changes in flux (growth rate) on the transcriptome, proteome, endometabolome and exometabolome of the yeast Saccharomyces cerevisiae. Each functional genomic level shows clear growth-rate-associated trends and discriminates between carbon-sufficient and carbon-limited conditions. Genes consistently and significantly upregulated with increasing growth rate are frequently essential and encode evolutionarily conserved proteins of known function that participate in many protein-protein interactions. In contrast, more unknown, and fewer essential, genes are downregulated with increasing growth rate; their protein products rarely interact with one another. A large proportion of yeast genes under positive growth-rate control share orthologs with other eukaryotes, including humans. Significantly, transcription of genes encoding components of the TOR complex (a major controller of eukaryotic cell growth) is not subject to growth-rate regulation. Moreover, integrative studies reveal the extent and importance of post-transcriptional control, patterns of control of metabolic fluxes at the level of enzyme synthesis, and the relevance of specific enzymatic reactions in the control of metabolic fluxes during cell growth. This work constitutes a first comprehensive systems biology study on growth-rate control in the eukaryotic cell. The results have direct implications for advanced studies on cell growth, in vivo regulation of metabolic fluxes for comprehensive metabolic engineering, and for the design of genome-scale systems biology models of the eukaryotic cell.

Antigen Potency and Maximal Efficacy Reveal a Mechanism of Efficient T Cell Activation

PubMed Central

Wheeler, Richard J.; Zhang, Hao; Cordoba, Shaun-Paul; Peng, Yan-Chun; Chen, Ji-Li; Cerundolo, Vincenzo; Dong, Tao; Coombs, Daniel; van der Merwe, P. Anton

2014-01-01

T cell activation, a critical event in adaptive immune responses, follows productive interactions between T cell receptors (TCRs) and antigens, in the form of peptide-bound major histocompatibility complexes (pMHCs) on the surfaces of antigen-presenting-cells. Upon activation, T cells can lyse infected cells, secrete cytokines, such as interferon-γ (IFN-γ), and perform other effector functions with various efficiencies that directly depend on the binding parameters of the TCR-pMHC complex. The mechanism that relates binding parameters to the efficiency of activation of the T cell remains controversial; some studies suggest that the dissociation constant (KD) determines the response (the “affinity model”), whereas others suggest that the off-rate (koff) is critical (the “productive hit rate model”). Here, we used mathematical modeling to show that antigen potency, as determined by the EC50, the functional correlate that is used to support KD-based models, could not be used to discriminate between the affinity and productive hit rate models. Our theoretical work showed that both models predicted a correlation between antigen potency and KD, but only the productive hit rate model predicted a correlation between maximal efficacy (Emax) and koff. We confirmed the predictions made by the productive hit rate model in experiments with cytotoxic T cell clones and a panel of pMHC variants. Therefore, we suggest that the activity of an antigen is determined by both its potency and maximal efficacy. We discuss the implications of our findings to the practical evaluation of T cell activation, for example in adoptive immunotherapies, and relate our work to the pharmacological theory of dose-response. PMID:21653229

Growth control of the eukaryote cell: a systems biology study in yeast

PubMed Central

Castrillo, Juan I; Zeef, Leo A; Hoyle, David C; Zhang, Nianshu; Hayes, Andrew; Gardner, David CJ; Cornell, Michael J; Petty, June; Hakes, Luke; Wardleworth, Leanne; Rash, Bharat; Brown, Marie; Dunn, Warwick B; Broadhurst, David; O'Donoghue, Kerry; Hester, Svenja S; Dunkley, Tom PJ; Hart, Sarah R; Swainston, Neil; Li, Peter; Gaskell, Simon J; Paton, Norman W; Lilley, Kathryn S; Kell, Douglas B; Oliver, Stephen G

2007-01-01

Background Cell growth underlies many key cellular and developmental processes, yet a limited number of studies have been carried out on cell-growth regulation. Comprehensive studies at the transcriptional, proteomic and metabolic levels under defined controlled conditions are currently lacking. Results Metabolic control analysis is being exploited in a systems biology study of the eukaryotic cell. Using chemostat culture, we have measured the impact of changes in flux (growth rate) on the transcriptome, proteome, endometabolome and exometabolome of the yeast Saccharomyces cerevisiae. Each functional genomic level shows clear growth-rate-associated trends and discriminates between carbon-sufficient and carbon-limited conditions. Genes consistently and significantly upregulated with increasing growth rate are frequently essential and encode evolutionarily conserved proteins of known function that participate in many protein-protein interactions. In contrast, more unknown, and fewer essential, genes are downregulated with increasing growth rate; their protein products rarely interact with one another. A large proportion of yeast genes under positive growth-rate control share orthologs with other eukaryotes, including humans. Significantly, transcription of genes encoding components of the TOR complex (a major controller of eukaryotic cell growth) is not subject to growth-rate regulation. Moreover, integrative studies reveal the extent and importance of post-transcriptional control, patterns of control of metabolic fluxes at the level of enzyme synthesis, and the relevance of specific enzymatic reactions in the control of metabolic fluxes during cell growth. Conclusion This work constitutes a first comprehensive systems biology study on growth-rate control in the eukaryotic cell. The results have direct implications for advanced studies on cell growth, in vivo regulation of metabolic fluxes for comprehensive metabolic engineering, and for the design of genome-scale systems biology models of the eukaryotic cell. PMID:17439666

Systematic Cell-Based Phenotyping of Missense Alleles Empowers Rare Variant Association Studies: A Case for LDLR and Myocardial Infarction

PubMed Central

Schuberth, Christian; Won, Hong-Hee; Blattmann, Peter; Joggerst-Thomalla, Brigitte; Theiss, Susanne; Asselta, Rosanna; Duga, Stefano; Merlini, Pier Angelica; Ardissino, Diego; Lander, Eric S.; Gabriel, Stacey; Rader, Daniel J.; Peloso, Gina M.; Kathiresan, Sekar; Runz, Heiko

2015-01-01

A fundamental challenge to contemporary genetics is to distinguish rare missense alleles that disrupt protein functions from the majority of alleles neutral on protein activities. High-throughput experimental tools to securely discriminate between disruptive and non-disruptive missense alleles are currently missing. Here we establish a scalable cell-based strategy to profile the biological effects and likely disease relevance of rare missense variants in vitro. We apply this strategy to systematically characterize missense alleles in the low-density lipoprotein receptor (LDLR) gene identified through exome sequencing of 3,235 individuals and exome-chip profiling of 39,186 individuals. Our strategy reliably identifies disruptive missense alleles, and disruptive-allele carriers have higher plasma LDL-cholesterol (LDL-C). Importantly, considering experimental data refined the risk of rare LDLR allele carriers from 4.5- to 25.3-fold for high LDL-C, and from 2.1- to 20-fold for early-onset myocardial infarction. Our study generates proof-of-concept that systematic functional variant profiling may empower rare variant-association studies by orders of magnitude. PMID:25647241

Proteomic Analysis of the Mediator Complex Interactome in Saccharomyces cerevisiae

PubMed Central

Uthe, Henriette; Vanselow, Jens T.; Schlosser, Andreas

2017-01-01

Here we present the most comprehensive analysis of the yeast Mediator complex interactome to date. Particularly gentle cell lysis and co-immunopurification conditions allowed us to preserve even transient protein-protein interactions and to comprehensively probe the molecular environment of the Mediator complex in the cell. Metabolic 15N-labeling thereby enabled stringent discrimination between bona fide interaction partners and nonspecifically captured proteins. Our data indicates a functional role for Mediator beyond transcription initiation. We identified a large number of Mediator-interacting proteins and protein complexes, such as RNA polymerase II, general transcription factors, a large number of transcriptional activators, the SAGA complex, chromatin remodeling complexes, histone chaperones, highly acetylated histones, as well as proteins playing a role in co-transcriptional processes, such as splicing, mRNA decapping and mRNA decay. Moreover, our data provides clear evidence, that the Mediator complex interacts not only with RNA polymerase II, but also with RNA polymerases I and III, and indicates a functional role of the Mediator complex in rRNA processing and ribosome biogenesis. PMID:28240253

Evaluation of several two-step scoring functions based on linear interaction energy, effective ligand size, and empirical pair potentials for prediction of protein-ligand binding geometry and free energy.

PubMed

Rahaman, Obaidur; Estrada, Trilce P; Doren, Douglas J; Taufer, Michela; Brooks, Charles L; Armen, Roger S

2011-09-26

The performances of several two-step scoring approaches for molecular docking were assessed for their ability to predict binding geometries and free energies. Two new scoring functions designed for "step 2 discrimination" were proposed and compared to our CHARMM implementation of the linear interaction energy (LIE) approach using the Generalized-Born with Molecular Volume (GBMV) implicit solvation model. A scoring function S1 was proposed by considering only "interacting" ligand atoms as the "effective size" of the ligand and extended to an empirical regression-based pair potential S2. The S1 and S2 scoring schemes were trained and 5-fold cross-validated on a diverse set of 259 protein-ligand complexes from the Ligand Protein Database (LPDB). The regression-based parameters for S1 and S2 also demonstrated reasonable transferability in the CSARdock 2010 benchmark using a new data set (NRC HiQ) of diverse protein-ligand complexes. The ability of the scoring functions to accurately predict ligand geometry was evaluated by calculating the discriminative power (DP) of the scoring functions to identify native poses. The parameters for the LIE scoring function with the optimal discriminative power (DP) for geometry (step 1 discrimination) were found to be very similar to the best-fit parameters for binding free energy over a large number of protein-ligand complexes (step 2 discrimination). Reasonable performance of the scoring functions in enrichment of active compounds in four different protein target classes established that the parameters for S1 and S2 provided reasonable accuracy and transferability. Additional analysis was performed to definitively separate scoring function performance from molecular weight effects. This analysis included the prediction of ligand binding efficiencies for a subset of the CSARdock NRC HiQ data set where the number of ligand heavy atoms ranged from 17 to 35. This range of ligand heavy atoms is where improved accuracy of predicted ligand efficiencies is most relevant to real-world drug design efforts.

Training on Movement Figure-Ground Discrimination Remediates Low-Level Visual Timing Deficits in the Dorsal Stream, Improving High-Level Cognitive Functioning, Including Attention, Reading Fluency, and Working Memory.

PubMed

Lawton, Teri; Shelley-Tremblay, John

2017-01-01

The purpose of this study was to determine whether neurotraining to discriminate a moving test pattern relative to a stationary background, figure-ground discrimination, improves vision and cognitive functioning in dyslexics, as well as typically-developing normal students. We predict that improving the speed and sensitivity of figure-ground movement discrimination ( PATH to Reading neurotraining) acts to remediate visual timing deficits in the dorsal stream, thereby improving processing speed, reading fluency, and the executive control functions of attention and working memory in both dyslexic and normal students who had PATH neurotraining more than in those students who had no neurotraining. This prediction was evaluated by measuring whether dyslexic and normal students improved on standardized tests of cognitive skills following neurotraining exercises, more than following computer-based guided reading ( Raz-Kids ( RK )). The neurotraining used in this study was visually-based training designed to improve magnocellular function at both low and high levels in the dorsal stream: the input to the executive control networks coding working memory and attention. This approach represents a paradigm shift from the phonologically-based treatment for dyslexia, which concentrates on high-level speech and reading areas. This randomized controlled-validation study was conducted by training the entire second and third grade classrooms (42 students) for 30 min twice a week before guided reading. Standardized tests were administered at the beginning and end of 12-weeks of intervention training to evaluate improvements in academic skills. Only movement-discrimination training remediated both low-level visual timing deficits and high-level cognitive functioning, including selective and sustained attention, reading fluency and working memory for both dyslexic and normal students. Remediating visual timing deficits in the dorsal stream revealed the causal role of visual movement discrimination training in improving high-level cognitive functions such as attention, reading acquisition and working memory. This study supports the hypothesis that faulty timing in synchronizing the activity of magnocellular with parvocellular visual pathways in the dorsal stream is a fundamental cause of dyslexia and being at-risk for reading problems in normal students, and argues against the assumption that reading deficiencies in dyslexia are caused by phonological or language deficits, requiring a paradigm shift from phonologically-based treatment of dyslexia to a visually-based treatment. This study shows that visual movement-discrimination can be used not only to diagnose dyslexia early, but also for its successful treatment, so that reading problems do not prevent children from readily learning.

Training on Movement Figure-Ground Discrimination Remediates Low-Level Visual Timing Deficits in the Dorsal Stream, Improving High-Level Cognitive Functioning, Including Attention, Reading Fluency, and Working Memory

PubMed Central

Lawton, Teri; Shelley-Tremblay, John

2017-01-01

The purpose of this study was to determine whether neurotraining to discriminate a moving test pattern relative to a stationary background, figure-ground discrimination, improves vision and cognitive functioning in dyslexics, as well as typically-developing normal students. We predict that improving the speed and sensitivity of figure-ground movement discrimination (PATH to Reading neurotraining) acts to remediate visual timing deficits in the dorsal stream, thereby improving processing speed, reading fluency, and the executive control functions of attention and working memory in both dyslexic and normal students who had PATH neurotraining more than in those students who had no neurotraining. This prediction was evaluated by measuring whether dyslexic and normal students improved on standardized tests of cognitive skills following neurotraining exercises, more than following computer-based guided reading (Raz-Kids (RK)). The neurotraining used in this study was visually-based training designed to improve magnocellular function at both low and high levels in the dorsal stream: the input to the executive control networks coding working memory and attention. This approach represents a paradigm shift from the phonologically-based treatment for dyslexia, which concentrates on high-level speech and reading areas. This randomized controlled-validation study was conducted by training the entire second and third grade classrooms (42 students) for 30 min twice a week before guided reading. Standardized tests were administered at the beginning and end of 12-weeks of intervention training to evaluate improvements in academic skills. Only movement-discrimination training remediated both low-level visual timing deficits and high-level cognitive functioning, including selective and sustained attention, reading fluency and working memory for both dyslexic and normal students. Remediating visual timing deficits in the dorsal stream revealed the causal role of visual movement discrimination training in improving high-level cognitive functions such as attention, reading acquisition and working memory. This study supports the hypothesis that faulty timing in synchronizing the activity of magnocellular with parvocellular visual pathways in the dorsal stream is a fundamental cause of dyslexia and being at-risk for reading problems in normal students, and argues against the assumption that reading deficiencies in dyslexia are caused by phonological or language deficits, requiring a paradigm shift from phonologically-based treatment of dyslexia to a visually-based treatment. This study shows that visual movement-discrimination can be used not only to diagnose dyslexia early, but also for its successful treatment, so that reading problems do not prevent children from readily learning. PMID:28555097

Plausibility assessment of a 2-state self-paced mental task-based BCI using the no-control performance analysis.

PubMed

Faradji, Farhad; Ward, Rabab K; Birch, Gary E

2009-06-15

The feasibility of having a self-paced brain-computer interface (BCI) based on mental tasks is investigated. The EEG signals of four subjects performing five mental tasks each are used in the design of a 2-state self-paced BCI. The output of the BCI should only be activated when the subject performs a specific mental task and should remain inactive otherwise. For each subject and each task, the feature coefficient and the classifier that yield the best performance are selected, using the autoregressive coefficients as the features. The classifier with a zero false positive rate and the highest true positive rate is selected as the best classifier. The classifiers tested include: linear discriminant analysis, quadratic discriminant analysis, Mahalanobis discriminant analysis, support vector machine, and radial basis function neural network. The results show that: (1) some classifiers obtained the desired zero false positive rate; (2) the linear discriminant analysis classifier does not yield acceptable performance; (3) the quadratic discriminant analysis classifier outperforms the Mahalanobis discriminant analysis classifier and performs almost as well as the radial basis function neural network; and (4) the support vector machine classifier has the highest true positive rates but unfortunately has nonzero false positive rates in most cases.

Color Discrimination Is Affected by Modulation of Luminance Noise in Pseudoisochromatic Stimuli

PubMed Central

Cormenzana Méndez, Iñaki; Martín, Andrés; Charmichael, Teaire L.; Jacob, Mellina M.; Lacerda, Eliza M. C. B.; Gomes, Bruno D.; Fitzgerald, Malinda E. C.; Ventura, Dora F.; Silveira, Luiz C. L.; O'Donell, Beatriz M.; Souza, Givago S.

2016-01-01

Pseudoisochromatic stimuli have been widely used to evaluate color discrimination and to identify color vision deficits. Luminance noise is one of the stimulus parameters used to ensure that subject's response is due to their ability to discriminate target stimulus from the background based solely on the hue between the colors that compose such stimuli. We studied the influence of contrast modulation of the stimulus luminance noise on threshold and reaction time color discrimination. We evaluated color discrimination thresholds using the Cambridge Color Test (CCT) at six different stimulus mean luminances. Each mean luminance condition was tested using two protocols: constant absolute difference between maximum and minimum luminance of the luminance noise (constant delta protocol, CDP), and constant contrast modulation of the luminance noise (constant contrast protocol, CCP). MacAdam ellipses were fitted to the color discrimination thresholds in the CIE 1976 color space to quantify the color discrimination ellipses at threshold level. The same CDP and CCP protocols were applied in the experiment measuring RTs at three levels of stimulus mean luminance. The color threshold measurements show that for the CDP, ellipse areas decreased as a function of the mean luminance and they were significantly larger at the two lowest mean luminances, 10 cd/m2 and 13 cd/m2, compared to the highest one, 25 cd/m2. For the CCP, the ellipses areas also decreased as a function of the mean luminance, but there was no significant difference between ellipses areas estimated at six stimulus mean luminances. The exponent of the decrease of ellipse areas as a function of stimulus mean luminance was steeper in the CDP than CCP. Further, reaction time increased linearly with the reciprocal of the length of the chromatic vectors varying along the four chromatic half-axes. It decreased as a function of stimulus mean luminance in the CDP but not in the CCP. The findings indicated that visual performance using pseudoisochromatic stimuli was dependent on the Weber's contrast of the luminance noise. Low Weber's contrast in the luminance noise is suggested to have a reduced effect on chromatic information and, hence, facilitate desegregation of the hue-defined target from the background. PMID:27458404

Auditory phase and frequency discrimination: a comparison of nine procedures.

PubMed

Creelman, C D; Macmillan, N A

1979-02-01

Two auditory discrimination tasks were thoroughly investigated: discrimination of frequency differences from a sinusoidal signal of 200 Hz and discrimination of differences in relative phase of mixed sinusoids of 200 Hz and 400 Hz. For each task psychometric functions were constructed for three observers, using nine different psychophysical measurement procedures. These procedures included yes-no, two-interval forced-choice, and various fixed- and variable-standard designs that investigators have used in recent years. The data showed wide ranges of apparent sensitivity. For frequency discrimination, models derived from signal detection theory for each psychophysical procedure seem to account for the performance differences. For phase discrimination the models do not account for the data. We conclude that for some discriminative continua the assumptions of signal detection theory are appropriate, and underlying sensitivity may be derived from raw data by appropriate transformations. For other continua the models of signal detection theory are probably inappropriate; we speculate that phase might be discriminable only on the basis of comparison or change and suggest some tests of our hypothesis.

Discrimination of osteoarthritic and rheumatoid human synovial cells in culture by nuclear image analysis.

PubMed

Delage, B; Giroud, F; Monet, J D; Ekindjian, O G; Cals, M J

1999-06-01

Rheumatoid arthritic (RA) and osteoarthritic (OA) synovial cells in culture differ in their metabolic and proliferative behaviour. To assess links between these properties and nuclear changes, we used image analysis to study chromatin texture, together with nuclear morphometry and densitometry of OA and RA cells in primary culture. Chromatin pattern at the third day (D3) was heterogeneous and granular with chromatin clumps whereas at the final stage (D11) of culture a homogeneous and finely granular chromatin texture was observed. This evolution indicates global chromatin decondensation. These characteristics were more marked for RA than for OA nuclei. At each culture time, RA nuclei could be discriminated with high confidence from OA ones from parameters evaluating the organization of the chromatine texture. Nuclear image analysis is thus a useful tool for investigating synovial cell biology.

Application of Fourier transform infrared spectroscopy and chemometrics for differentiation of Salmonella enterica serovar Enteritidis phage types.

PubMed

Preisner, Ornella; Guiomar, Raquel; Machado, Jorge; Menezes, José Cardoso; Lopes, João Almeida

2010-06-01

Fourier transform infrared (FT-IR) spectroscopy and chemometric techniques were used to discriminate five closely related Salmonella enterica serotype Enteritidis phage types, phage type 1 (PT1), PT1b, PT4b, PT6, and PT6a. Intact cells and outer membrane protein (OMP) extracts from bacterial cell membranes were subjected to FT-IR analysis in transmittance mode. Spectra were collected over a wavenumber range from 4,000 to 600 cm(-1). Partial least-squares discriminant analysis (PLS-DA) was used to develop calibration models based on preprocessed FT-IR spectra. The analysis based on OMP extracts provided greater separation between the Salmonella Enteritidis PT1-PT1b, PT4b, and PT6-PT6a groups than the intact cell analysis. When these three phage type groups were considered, the method based on OMP extract FT-IR spectra was 100% accurate. Moreover, complementary local models that considered only the PT1-PT1b and PT6-PT6a groups were developed, and the level of discrimination increased. PT1 and PT1b isolates were differentiated successfully with the local model using the entire OMP extract spectrum (98.3% correct predictions), whereas the accuracy of discrimination between PT6 and PT6a isolates was 86.0%. Isolates belonging to different phage types (PT19, PT20, and PT21) were used with the model to test its robustness. For the first time it was demonstrated that FT-IR analysis of OMP extracts can be used for construction of robust models that allow fast and accurate discrimination of different Salmonella Enteritidis phage types.

The machinery of Nod-like receptors: refining the paths to immunity and cell death.

PubMed

Saleh, Maya

2011-09-01

One of the fundamental aspects of the innate immune system is its capacity to discriminate between self and non-self or altered self, and to quickly respond by eliciting effector mechanisms that act in concert to restore normalcy. This capacity is determined by a set of evolutionarily conserved pattern recognition receptors (PRRs) that sense the presence of microbial motifs or endogenous danger signals, including tissue damage, cellular transformation or metabolic perturbation, and orchestrate the nature, duration and intensity of the innate immune response. Nod-like receptors (NLRs), a group of intracellular PRRs, are particularly essential as evident by the high incidence of genetic variations in their genes in various diseases of homeostasis. Here, I overview the signaling mechanisms of NLRs and discuss the mounting evidence of evolutionary conservation between their pathways and the cell death machinery. I also describe their effector functions that link the sensing of danger to the induction of inflammation, autophagy or cell death. © 2011 John Wiley & Sons A/S.

Behavioral and neurochemical pharmacology of six psychoactive substituted phenethylamines: mouse locomotion, rat drug discrimination and in vitro receptor and transporter binding and function.

PubMed

Eshleman, Amy J; Forster, Michael J; Wolfrum, Katherine M; Johnson, Robert A; Janowsky, Aaron; Gatch, Michael B

2014-03-01

Psychoactive-substituted phenethylamines 2,5-dimethoxy-4-chlorophenethylamine (2C-C); 2,5-dimethoxy-4-methylphenethylamine (2C-D); 2,5-dimethoxy-4-ethylphenethylamine (2C-E); 2,5-dimethoxy-4-iodophenethylamine (2C-I); 2,5-dimethoxy-4-ethylthiophenethylamine (2C-T-2); and 2,5-dimethoxy-4-chloroamphetamine (DOC) are used recreationally and may have deleterious side effects. This study compares the behavioral effects and the mechanisms of action of these substituted phenethylamines with those of hallucinogens and a stimulant. The effects of these compounds on mouse locomotor activity and in rats trained to discriminate dimethyltryptamine, (-)-DOM, (+)-LSD, (±)-MDMA, and S(+)-methamphetamine were assessed. Binding and functional activity of the phenethylamines at 5-HT1A, 5-HT2A, 5-HT2C receptors and monoamine transporters were assessed using cells heterologously expressing these proteins. The phenethylamines depressed mouse locomotor activity, although 2C-D and 2C-E stimulated activity at low doses. The phenethylamines except 2C-T-2 fully substituted for at least one hallucinogenic training compound, but none fully substituted for (+)-methamphetamine. At 5-HT1A receptors, only 2C-T-2 and 2C-I were partial-to-full very low potency agonists. In 5-HT2A arachidonic acid release assays, the phenethylamines were partial to full agonists except 2C-I which was an antagonist. All compounds were full agonists at 5-HT2A and 5-HT2C receptor inositol phosphate assays. Only 2C-I had moderate affinity for, and very low potency at, the serotonin transporter. The discriminative stimulus effects of 2C-C, 2C-D, 2C-E, 2C-I, and DOC were similar to those of several hallucinogens, but not methamphetamine. Additionally, the substituted phenethylamines were full agonists at 5-HT2A and 5-HT2C receptors, but for 2C-T-2, this was not sufficient to produce hallucinogen-like discriminative stimulus effects. Additionally, the 5-HT2A inositol phosphate pathway may be important in 2C-I's psychoactive properties.

Behavioral and neurochemical pharmacology of six psychoactive substituted phenethylamines: Mouse locomotion, rat drug discrimination and in vitro receptor and transporter binding and function

PubMed Central

Eshleman, Amy J.; Forster, Michael J.; Wolfrum, Katherine M.; Johnson, Robert A.; Janowsky, Aaron; Gatch, Michael B.

2014-01-01

Rationale Psychoactive substituted phenethylamines 2,5-dimethoxy-4-chlorophenethylamine (2C-C); 2,5-dimethoxy-4-methylphenethylamine (2C-D); 2,5-dimethoxy-4-ethylphenethylamine (2C-E); 2,5-dimethoxy-4-iodophenethylamine (2C-I); 2,5-dimethoxy-4-ethylthiophenethylamine (2C-T-2) and 2,5-dimethoxy-4-chloroamphetamine (DOC) are used recreationally and may have deleterious side effects. Objectives This study compares behavioral effects and mechanisms of action of these substituted phenethylamines with those of hallucinogens and a stimulant. Methods The effects of these compounds on mouse locomotor activity and in rats trained to discriminate dimethyltryptamine, (−)DOM, (+)LSD, (±)MDMA and (S+)methamphetamine were assessed. Binding and functional activity of the phenethylamines at 5-HT1A, 5-HT2A, 5-HT2C receptors and monoamine transporters were assessed using cells heterologously expressing these proteins. Results The phenethylamines depressed mouse locomotor activity, although 2C-D and 2C-E stimulated activity at low doses. The phenethylamines except 2C-T-2 fully substituted for at least one hallucinogenic training compound but none fully substituted for (+)-methamphetamine. At 5-HT1A receptors, only 2C-T-2 and 2C-I were partial-to-full very low potency agonists. In 5-HT2A arachidonic acid release assays, the phenethylamines were partial to full agonists except 2C-I which was an antagonist. All compounds were full agonists at 5-HT2A and 5-HT2C receptor inositol phosphate assays. Only 2C-I had moderate affinity for, and very low potency at, the serotonin transporter. Conclusions The discriminative stimulus effects of 2C-C, 2C-D, 2C-E, 2C-I and DOC were similar to those of several hallucinogens but not methamphetamine. Additionally, the substituted phenethylamines were full agonists at 5-HT2A and 5-HT2C receptors, but for 2C-T-2, this was not sufficient to produce hallucinogenlike discriminative stimulus effects. Additionally, the 5-HT2A inositol phosphate pathway may be important in 2C-I’s psychoactive properties. PMID:24142203

AII amacrine cells discriminate between heterocellular and homocellular locations when assembling connexin36-containing gap junctions

PubMed Central

Meyer, Arndt; Hilgen, Gerrit; Dorgau, Birthe; Sammler, Esther M.; Weiler, Reto; Monyer, Hannah; Dedek, Karin; Hormuzdi, Sheriar G.

2014-01-01

ABSTRACT Electrical synapses (gap junctions) rapidly transmit signals between neurons and are composed of connexins. In neurons, connexin36 (Cx36) is the most abundant isoform; however, the mechanisms underlying formation of Cx36-containing electrical synapses are unknown. We focus on homocellular and heterocellular gap junctions formed by an AII amacrine cell, a key interneuron found in all mammalian retinas. In mice lacking native Cx36 but expressing a variant tagged with enhanced green fluorescent protein at the C-terminus (KO-Cx36-EGFP), heterocellular gap junctions formed between AII cells and ON cone bipolar cells are fully functional, whereas homocellular gap junctions between two AII cells are not formed. A tracer injected into an AII amacrine cell spreads into ON cone bipolar cells but is excluded from other AII cells. Reconstruction of Cx36–EGFP clusters on an AII cell in the KO-Cx36-EGFP genotype confirmed that the number, but not average size, of the clusters is reduced – as expected for AII cells lacking a subset of electrical synapses. Our studies indicate that some neurons exhibit at least two discriminatory mechanisms for assembling Cx36. We suggest that employing different gap-junction-forming mechanisms could provide the means for a cell to regulate its gap junctions in a target-cell-specific manner, even if these junctions contain the same connexin. PMID:24463820

Multiple Levels of Suffering

PubMed Central

Kiley, Kasey B.; Haywood, Carlton; Bediako, Shawn M.; Lanzkron, Sophie; Carroll, C. Patrick; Buenaver, Luis F.; Pejsa, Megan; Edwards, Robert R.; Haythornthwaite, Jennifer A.; Campbell, Claudia M.

2016-01-01

Objective: People living with sickle cell disease (SCD) experience severe episodic and chronic pain and frequently report poor interpersonal treatment within health-care settings. In this particularly relevant context, we examined the relationship between perceived discrimination and both clinical and laboratory pain. Methods: Seventy-one individuals with SCD provided self-reports of experiences with discrimination in health-care settings and clinical pain severity, and completed a psychophysical pain testing battery in the laboratory. Results: Discrimination in health-care settings was correlated with greater clinical pain severity and enhanced sensitivity to multiple laboratory-induced pain measures, as well as stress, depression, and sleep. After controlling for relevant covariates, discrimination remained a significant predictor of mechanical temporal summation (a marker of central pain facilitation), but not clinical pain severity or suprathreshold heat pain response. Furthermore, a significant interaction between experience with discrimination and clinical pain severity was associated with mechanical temporal summation; increased experience with discrimination was associated with an increased correlation between clinical pain severity and temporal summation of pain. Discussion: Perceived discrimination within health-care settings was associated with pain facilitation. These findings suggest that discrimination may be related to increased central sensitization among SCD patients, and more broadly that health-care social environments may interact with pain pathophysiology. PMID:26889615

Discriminating cellular heterogeneity using microwell-based RNA cytometry

PubMed Central

Dimov, Ivan K.; Lu, Rong; Lee, Eric P.; Seita, Jun; Sahoo, Debashis; Park, Seung-min; Weissman, Irving L.; Lee, Luke P.

2014-01-01

Discriminating cellular heterogeneity is important for understanding cellular physiology. However, it is limited by the technical difficulties of single-cell measurements. Here, we develop a two-stage system to determine cellular heterogeneity. In the first stage, we perform multiplex single-cell RNA-cytometry in a microwell array containing over 60,000 reaction chambers. In the second stage, we use the RNA-cytometry data to determine cellular heterogeneity by providing a heterogeneity likelihood score. Moreover, we use Monte-Carlo simulation and RNA-cytometry data to calculate the minimum number of cells required for detecting heterogeneity. We applied this system to characterize the RNA distributions of aging related genes in a highly purified mouse hematopoietic stem cell population. We identified genes that reveal novel heterogeneity of these cells. We also show that changes in expression of genes such as Birc6 during aging can be attributed to the shift of relative portions of cells in the high-expressing subgroup versus low-expressing subgroup. PMID:24667995

ELISPOTs Produced by CD8 and CD4 Cells Follow Log Normal Size Distribution Permitting Objective Counting

PubMed Central

Karulin, Alexey Y.; Karacsony, Kinga; Zhang, Wenji; Targoni, Oleg S.; Moldovan, Ioana; Dittrich, Marcus; Sundararaman, Srividya; Lehmann, Paul V.

2015-01-01

Each positive well in ELISPOT assays contains spots of variable sizes that can range from tens of micrometers up to a millimeter in diameter. Therefore, when it comes to counting these spots the decision on setting the lower and the upper spot size thresholds to discriminate between non-specific background noise, spots produced by individual T cells, and spots formed by T cell clusters is critical. If the spot sizes follow a known statistical distribution, precise predictions on minimal and maximal spot sizes, belonging to a given T cell population, can be made. We studied the size distributional properties of IFN-γ, IL-2, IL-4, IL-5 and IL-17 spots elicited in ELISPOT assays with PBMC from 172 healthy donors, upon stimulation with 32 individual viral peptides representing defined HLA Class I-restricted epitopes for CD8 cells, and with protein antigens of CMV and EBV activating CD4 cells. A total of 334 CD8 and 80 CD4 positive T cell responses were analyzed. In 99.7% of the test cases, spot size distributions followed Log Normal function. These data formally demonstrate that it is possible to establish objective, statistically validated parameters for counting T cell ELISPOTs. PMID:25612115

Do mechanical forces contribute to nanoscale membrane organisation in T cells?

PubMed

Klotzsch, Enrico; Stiegler, Johannes; Ben-Ishay, Eldad; Gaus, Katharina

2015-04-01

Mechanotransduction describes how a cell senses and interacts with its environment. The concept originated in adhesion biology where adhesion receptors, integrins, facilitate force transmission between the extracellular matrix and the intracellular actin cytoskeleton. Indeed, during any adhesive contacts, cells do exert mechanical force. Hence, the probing of the local environment by cells results in mechanical cues that contribute to cellular functions and cell fate decisions such as migration, proliferation, differentiation and apoptosis. On the molecular level, mechanical forces can rearrange proteins laterally within the membrane, regulate their activity by inducing conformational changes and probe the mechanical properties and bond strength of receptor-ligands. From this point of view, it appears surprising that molecular forces have been largely overlooked in membrane organisation and ligand discrimination processes in lymphocytes. During T cell activation, the T cell receptor recognises and distinguishes antigenic from benign endogenous peptides to initiate the reorganisation of membrane proteins into signalling clusters within the immunological synapse. In this review, we asked whether characteristics of fibroblast force sensing could be applied to immune cell antigen recognition and signalling, and outline state-of-the-art experimental strategies for studying forces in the context of membrane organisation. This article is part of a Special Issue entitled: Nanoscale membrane orgainisation and signalling. Copyright © 2014 Elsevier B.V. All rights reserved.

The predictive value of mean platelet volume, plateletcrit and red cell distribution width in the differentiation of autoimmune gastritis patients with and without type I gastric carcinoid tumors.

PubMed

Tüzün, Ali; Keskin, Onur; Yakut, Mustafa; Kalkan, Cagdas; Soykan, Irfan

2014-01-01

Autoimmune gastritis is an autoimmune and inflammatory condition that may predispose to gastric carcinoid tumors or adenocarcinomas. The early diagnosis of these tumors is important in order to decrease morbidity and mortality. Platelet indices such as mean platelet volume and plateletcrit levels increase in inflammatory, infectious and malign conditions. The primary aim of this study was to explore wheter platelet indices and red cell distribution width have any predictive role in the discrimination of autoimmune gastritis patients with and without gastric carcinoid tumors. Also secondary aim of this study was to investigate whether any changes exist betwenn autoimmune gastritis and functional dyspepsia patients by means of platelet indices. Plateletcrit (0.22 ± 0.06 vs. 0.20 ± 0.03%, p < 0.001) and red cell distribution width (16.11 ± 3.04 vs. 13.41 ± 0.95%, p < 0.001) were significantly higher in autoimmune gastritis patients compared to control group. Receiver operating curve analysis suggested that optimum plateletcrit cut-off point was 0.20% (AUC: 0.646), and 13.95% as the cut off value for red cell distribution width (AUC: 0.860). Although plateletcrit (0.22 ± 0.06 vs. 0.21 ± 0.04%, p = 0.220) and mean platelet volume (8.94 ± 1.44 vs. 8.68 ± 0.89 fl, p = 0.265) were higher in autoimmune gastritis patients without carcinoid tumor compared to patients with carcinoid tumors, these parameters were not statistically significant. Changes in plateletcrit and red cell distribution width values may be used as a marker in the discrimination of autoimmune gastritis and fucntional dyspepsia patients but not useful in patients with gastric carcinoid tumor type I.

Localisation of the Putative Magnetoreceptive Protein Cryptochrome 1b in the Retinae of Migratory Birds and Homing Pigeons.

PubMed

Bolte, Petra; Bleibaum, Florian; Einwich, Angelika; Günther, Anja; Liedvogel, Miriam; Heyers, Dominik; Depping, Anne; Wöhlbrand, Lars; Rabus, Ralf; Janssen-Bienhold, Ulrike; Mouritsen, Henrik

2016-01-01

Cryptochromes are ubiquitously expressed in various animal tissues including the retina. Some cryptochromes are involved in regulating circadian activity. Cryptochrome proteins have also been suggested to mediate the primary mechanism in light-dependent magnetic compass orientation in birds. Cryptochrome 1b (Cry1b) exhibits a unique carboxy terminus exclusively found in birds so far, which might be indicative for a specialised function. Cryptochrome 1a (Cry1a) is so far the only cryptochrome protein that has been localised to specific cell types within the retina of migratory birds. Here we show that Cry1b, an alternative splice variant of Cry1a, is also expressed in the retina of migratory birds, but it is primarily located in other cell types than Cry1a. This could suggest different functions for the two splice products. Using diagnostic bird-specific antibodies (that allow for a precise discrimination between both proteins), we show that Cry1b protein is found in the retinae of migratory European robins (Erithacus rubecula), migratory Northern Wheatears (Oenanthe oenanthe) and pigeons (Columba livia). In all three species, retinal Cry1b is localised in cell types which have been discussed as potentially well suited locations for magnetoreception: Cry1b is observed in the cytosol of ganglion cells, displaced ganglion cells, and in photoreceptor inner segments. The cytosolic rather than nucleic location of Cry1b in the retina reported here speaks against a circadian clock regulatory function of Cry1b and it allows for the possible involvement of Cry1b in a radical-pair-based magnetoreception mechanism.

Distinctions between organic brain syndrome and functional psychiatric disorders: based on the geriatric mental state interview.

PubMed

Fleiss, J; Gurland, B; Roche, P D

1976-01-01

Discriminant function analysis was employed to study the ability of the Geriatric Mental Status interview to distinguish between patients diagnosed by the project as having an organic brain syndrome or a functional psychiatric disorder. In both New York and London, patients with organic brain syndrome scored significantly higher (p less than 0.05) than those with functional disorders on the factors of impaired memory, disorientation and incomprehensibility and significantly lower on the factors of depression and somatic concerns. Discriminant functions calculated from data on the New York and London patients separately significantly distinguished not only the patients on whom the functions were based but the patients in the other sample as well.

Mutation that blocks ATP binding creates a pseudokinase stabilizing the scaffolding function of kinase suppressor of Ras, CRAF and BRAF.

PubMed

Hu, Jiancheng; Yu, Haiyang; Kornev, Alexandr P; Zhao, Jianping; Filbert, Erin L; Taylor, Susan S; Shaw, Andrey S

2011-04-12

Because mutations in RAS and BRAF represent the most common mutations found in human tumors, identification of inhibitors has been a major goal. Surprisingly, new oncogenic BRAF specific inhibitors inhibit cells transformed with mutated BRAF but paradoxically stimulate the growth of cells transformed with RAS. Here, we show that the mechanism for activation is via drug-induced dimer formation between CRAF and kinase suppressor of Ras (KSR)1. To understand the function of KSR1, we generated a KSR1 mutant that cannot bind ATP but stabilizes the closed, active conformation of KSR1. Molecular modeling suggested that the mutant stabilizes the two hydrophobic spines critical for the closed active conformation. We, therefore, could use the mutant to discriminate between the scaffold versus kinase functions of KSR1. The KSR1 mutant bound constitutively to RAF and mitogen-activated protein kinase kinase (MEK) but could not reconstitute activity suggesting that the catalytic activity of KSR1 is required for its function. Analogous mutations in BRAF and CRAF allowed us to test the generality of the model. The mutation induced changes consistent with the active, closed conformation of both kinases and confirmed that BRAF functions distinctly from CRAF in the MAP kinase pathway. Not only does this work suggest that KSR1 may function as a kinase, we anticipate that the mutation that we generated may be broadly applicable to stabilize the closed conformation of other kinases many of which may also form dimers.

Nascent RNA kinetics: Transient and steady state behavior of models of transcription

NASA Astrophysics Data System (ADS)

Choubey, Sandeep

2018-02-01

Regulation of transcription is a vital process in cells, but mechanistic details of this regulation still remain elusive. The dominant approach to unravel the dynamics of transcriptional regulation is to first develop mathematical models of transcription and then experimentally test the predictions these models make for the distribution of mRNA and protein molecules at the individual cell level. However, these measurements are affected by a multitude of downstream processes which make it difficult to interpret the measurements. Recent experimental advancements allow for counting the nascent mRNA number of a gene as a function of time at the single-inglr cell level. These measurements closely reflect the dynamics of transcription. In this paper, we consider a general mechanism of transcription with stochastic initiation and deterministic elongation and probe its impact on the temporal behavior of nascent RNA levels. Using techniques from queueing theory, we derive exact analytical expressions for the mean and variance of the nascent RNA distribution as functions of time. We apply these analytical results to obtain the mean and variance of nascent RNA distribution for specific models of transcription. These models of initiation exhibit qualitatively distinct transient behaviors for both the mean and variance which further allows us to discriminate between them. Stochastic simulations confirm these results. Overall the analytical results presented here provide the necessary tools to connect mechanisms of transcription initiation to single-cell measurements of nascent RNA.

Surface-Enhanced Raman Scattering (SERS) in Microbiology: Illumination and Enhancement of the Microbial World.

PubMed

Chisanga, Malama; Muhamadali, Howbeer; Ellis, David I; Goodacre, Royston

2018-01-01

The microbial world forms a huge family of organisms that exhibit the greatest phylogenetic diversity on Earth and thus colonize virtually our entire planet. Due to this diversity and subsequent complex interactions, the vast majority of microorganisms are involved in innumerable natural bioprocesses and contribute an absolutely vital role toward the maintenance of life on Earth, whilst a small minority cause various infectious diseases. The ever-increasing demand for environmental monitoring, sustainable ecosystems, food security, and improved healthcare systems drives the continuous search for inexpensive but reproducible, automated and portable techniques for detection of microbial isolates and understanding their interactions for clinical, environmental, and industrial applications and benefits. Surface-enhanced Raman scattering (SERS) is attracting significant attention for the accurate identification, discrimination and characterization and functional assessment of microbial cells at the single cell level. In this review, we briefly discuss the technological advances in Raman and Fourier transform infrared (FT-IR) instrumentation and their application for the analysis of clinically and industrially relevant microorganisms, biofilms, and biological warfare agents. In addition, we summarize the current trends and future prospects of integrating Raman/SERS-isotopic labeling and cell sorting technologies in parallel, to link genotype-to-phenotype in order to define community function of unculturable microbial cells in mixed microbial communities which possess admirable traits such as detoxification of pollutants and recycling of essential metals.

Corona discharge radical emission spectroscopy: a multi-channel detector with nose-type function for discrimination analysis.

PubMed

Tian, Yunfei; Wu, Peng; Wu, Xi; Jiang, Xiaoming; Xu, Kailai; Hou, Xiandeng

2013-04-21

A simple and economical multi-channel optical sensor using corona discharge radical emission spectroscopy is developed and explored as an optical nose for discrimination analysis of volatile organic compounds, wines, and even isomers.

3D Texture Analysis in Renal Cell Carcinoma Tissue Image Grading

PubMed Central

Cho, Nam-Hoon; Choi, Heung-Kook

2014-01-01

One of the most significant processes in cancer cell and tissue image analysis is the efficient extraction of features for grading purposes. This research applied two types of three-dimensional texture analysis methods to the extraction of feature values from renal cell carcinoma tissue images, and then evaluated the validity of the methods statistically through grade classification. First, we used a confocal laser scanning microscope to obtain image slices of four grades of renal cell carcinoma, which were then reconstructed into 3D volumes. Next, we extracted quantitative values using a 3D gray level cooccurrence matrix (GLCM) and a 3D wavelet based on two types of basis functions. To evaluate their validity, we predefined 6 different statistical classifiers and applied these to the extracted feature sets. In the grade classification results, 3D Haar wavelet texture features combined with principal component analysis showed the best discrimination results. Classification using 3D wavelet texture features was significantly better than 3D GLCM, suggesting that the former has potential for use in a computer-based grading system. PMID:25371701

[The research of establishing discriminant function for patients with angina pectoris by stepwise analysis based on serum inflammatory factors].

PubMed

Chen, Zhi-bin; Liang, Yan-bing; Tang, Hao; Wang, Zhong-hua; Zeng, Li-jin; Wu, Jing-guo; Li, Zhen-yu; Ma, Zhong-fu

2012-12-01

To improve cost-efficiency, discriminant functions in stepwise method was founded for the differential diagnosis of angina pectoris by detecting the serum level of high-sensitivity C-reactive protein (hs-CRP), macrophage migration inhibitory factor (MIF), interleukin-4 (IL-4) and interleukin-10 (IL-10) in patients with stable angina pectoris (SAP) and unstable angina pectoris (UAP). Thirty-nine SAP patients and 47 UAP patients were enrolled into the study, while 39 healthy volunteers were enrolled into the controlled group forming the entire set of training samples. The serum levels of hs-CRP, MIF, IL-4 and IL-10 were measured by enzyme linked immunosorbent assay (ELISA). Data was analyzed by software to define discriminant functions in the ways of "entering" and "stepwise". Both functions were evaluated by the results of validation. By the way of "enter independent together", the following discriminant functions were defined based on the data of training samples' age, hs-CRP, MIF, IL-4, IL-10: healthy control group =-129.858 + 2.869×age -2.451×hs-CRP + 1.393×MIF + 6.001×IL-4 + 4.848×IL-10; SAP group=-161.037 + 2.896×age-2.022×hs-CRP + 1.662×MIF + 6.703×IL-4 + 6.287×IL-10; UAP group=-199.087 + 2.468×age-1.440×hs-CRP + 3.404×MIF-13.875×IL-4 + 7.752×IL-10. Retrospective validation showed 4.8% of total miss-grouping, while cross-validation showed 5.6% of total miss-grouping. By the way of "stepwise", the above data was screened by software and training samples' age, MIF and IL-10 were suggested to define the following functions: healthy control group = - 125.218 + 2.659 × age + 0.599×MIF + 5.040 × IL-10; SAP group=-157.864 + 2.721×age + 1.008×MIF + 6.468×IL-10; UAP group=- 197.327 + 2.360×age + 2.932×MIF + 7.640×IL-10. Both retrospective and cross validation showed 6.4% of total miss-grouping. Both sets of discriminant functions had the same efficiency (100%) for differential diagnosis of SAP and UAP. The discriminant functions based on samples' age, MIF and IL-10, which were screened and suggested by stepwise method, may contribute to the differential diagnosis of atypical SAP and UAP, and therefore demonstrate better cost-efficiency.

Symptom Discrimination and Habituation: A Case Study of Behavioral Treatment for Postural Orthostatic Tachycardia Syndrome (POTS).

PubMed

Ralston, Timothy E; Kanzler, Kathryn E

2016-01-01

Postural orthostatic tachycardia syndrome (POTS) is a multifaceted disorder of the autonomic nervous system that profoundly impacts physical functioning. In addition to physical consequences, many patients develop situational anxiety that causes reduced activity level, which may impede functional recovery from POTS. Despite links with anxiety, to date there have been no reports of psychological intervention for POTS. Here we report a case study of POTS in a 40-year-old female serving on active duty in the US military. Because there are no established guidelines for the psychological treatment of POTS, intervention techniques were adapted for use with the patient. Elements of cognitive behavioral therapy, including in-vivo exposure and symptom discrimination, were used to target avoidance of feared situations. Over the course of treatment, the patient learned to discriminate her POTS symptoms from anxiety and displayed a significant decrease in POTS-related functional impairment. Implications for future care are discussed.

[Visual perception and its disorders].

PubMed

Ruf-Bächtiger, L

1989-11-21

It's the brain and not the eye that decides what is perceived. In spite of this fact, quite a lot is known about the functioning of the eye and the first sections of the optic tract, but little about the actual process of perception. Examination of visual perception and its malfunctions relies therefore on certain hypotheses. Proceeding from the model of functional brain systems, variant functional domains of visual perception can be distinguished. Among the more important of these domains are: digit span, visual discrimination and figure-ground discrimination. Evaluation of these functional domains allows us to understand those children with disorders of visual perception better and to develop more effective treatment methods.

Transcriptional profiles discriminate patients with pulmonary tuberculosis from non-tuberculous individuals depending on the presence of non-insulin diabetes mellitus.

PubMed

Serrano, Carmen J; Cuevas-Córdoba, Betzaida; Macías-Segura, Noé; González-Curiel, Rosa Angélica; Martínez-Balderas, Víctor Yordani; Enciso-Moreno, Leonor; Small, Peter; Hernández-Pando, Rogelio; Enciso-Moreno, José Antonio

2016-01-01

Our objective was to identify transcriptional biomarkers in peripheral blood mononuclear cells (PBMC) that discriminate individuals with latent tuberculosis infection (LTBI) from those with pulmonary tuberculosis (PTB) in subjects with non-insulin-dependent diabetes mellitus (NIDDM) and in individuals without NIDDM. Using gene expression microarrays we identified differentially expressed genes from lungs of mice infected with Mycobacterium tuberculosis (Mtb) or a mutant (ΔsigH) representing a non-inflammatory model. Genes expressed in blood, with inflammatory related functions were evaluated in humans by RT-qPCR. NCF1 and ORM transcripts have the better discriminatory capacity to identify PTB subjects from LTBI and non-infected controls (NICs) independently of the presence of NIDDM. The sequential evaluation of the mRNA levels of NCF1 and ORM as multiple diagnostic tests showed 95% Sensitivity (Se) and 80% Specificity (Sp). In addition, FPR2 promises to be a good biomarker for the PTB detection in subjects with NIDDM (Se=100%; Sp=90%). Copyright © 2015 Elsevier Inc. All rights reserved.

From innervation density to tactile acuity: 1. Spatial representation.

PubMed

Brown, Paul B; Koerber, H Richard; Millecchia, Ronald

2004-06-11

We tested the hypothesis that the population receptive field representation (a superposition of the excitatory receptive field areas of cells responding to a tactile stimulus) provides spatial information sufficient to mediate one measure of static tactile acuity. In psychophysical tests, two-point discrimination thresholds on the hindlimbs of adult cats varied as a function of stimulus location and orientation, as they do in humans. A statistical model of the excitatory low threshold mechanoreceptive fields of spinocervical, postsynaptic dorsal column and spinothalamic tract neurons was used to simulate the population receptive field representations in this neural population of the one- and two-point stimuli used in the psychophysical experiments. The simulated and observed thresholds were highly correlated. Simulated and observed thresholds' relations to physiological and anatomical variables such as stimulus location and orientation, receptive field size and shape, map scale, and innervation density were strikingly similar. Simulated and observed threshold variations with receptive field size and map scale obeyed simple relationships predicted by the signal detection model, and were statistically indistinguishable from each other. The population receptive field representation therefore contains information sufficient for this discrimination.

Chapter 6: cubic membranes the missing dimension of cell membrane organization.

PubMed

Almsherqi, Zakaria A; Landh, Tomas; Kohlwein, Sepp D; Deng, Yuru

2009-01-01

Biological membranes are among the most fascinating assemblies of biomolecules: a bilayer less than 10 nm thick, composed of rather small lipid molecules that are held together simply by noncovalent forces, defines the cell and discriminates between "inside" and "outside", survival, and death. Intracellular compartmentalization-governed by biomembranes as well-is a characteristic feature of eukaryotic cells, which allows them to fulfill multiple and highly specialized anabolic and catabolic functions in strictly controlled environments. Although cellular membranes are generally visualized as flat sheets or closely folded isolated objects, multiple observations also demonstrate that membranes may fold into "unusual", highly organized structures with 2D or 3D periodicity. The obvious correlation of highly convoluted membrane organizations with pathological cellular states, for example, as a consequence of viral infection, deserves close consideration. However, knowledge about formation and function of these highly organized 3D periodic membrane structures is scarce, primarily due to the lack of appropriate techniques for their analysis in vivo. Currently, the only direct way to characterize cellular membrane architecture is by transmission electron microscopy (TEM). However, deciphering the spatial architecture solely based on two-dimensionally projected TEM images is a challenging task and prone to artifacts. In this review, we will provide an update on the current progress in identifying and analyzing 3D membrane architectures in biological systems, with a special focus on membranes with cubic symmetry, and their potential role in physiological and pathophysiological conditions. Proteomics and lipidomics approaches in defined experimental cell systems may prove instrumental to understand formation and function of 3D membrane morphologies.

The role of the inhibitors of interleukin-6 signal transduction SHP2 and SOCS3 for desensitization of interleukin-6 signalling.

PubMed Central

Fischer, Patrick; Lehmann, Ute; Sobota, Radoslaw M; Schmitz, Jochen; Niemand, Claudia; Linnemann, Sonja; Haan, Serge; Behrmann, Iris; Yoshimura, Akihiko; Johnston, James A; Müller-Newen, Gerhard; Heinrich, Peter C; Schaper, Fred

2004-01-01

The immediate early response of cells treated with IL-6 (interleukin-6) is the activation of the signal transducer and activator of transcription (STAT)3. The Src homology domain 2 (SH2)-containing protein tyrosine phosphatase SHP2 and the feedback inhibitor SOCS3 (suppressor of cytokine signalling) are potent inhibitors of IL-6 signal transduction. Impaired function of SOCS3 or SHP2 leads to enhanced and prolonged IL-6 signalling. The inhibitory function of both proteins depends on their recruitment to the tyrosine motif 759 within glycoprotein gp130. In contrast to inactivation, desensitization of signal transduction is regarded as impaired responsiveness due to prestimulation. Usually, after activation the sensing receptor becomes inactivated by modifications such as phosphorylation, internalization or degradation. We designed an experimental approach which allows discrimination between desensitization and inactivation of IL-6 signal transduction. We observed that pre-stimulation with IL-6 renders cells less sensitive to further stimulation with IL-6. After several hours, the cells become sensitive again. We show that not only signal transduction through previously activated receptors is affected by desensitization but signalling through receptors which were not targeted by the first stimulation was also attenuated ( trans -desensitization). Interestingly, in contrast to inhibition, desensitization does not depend on the presence of functional SHP2. Furthermore, cells lacking SOCS3 show constitutive STAT3 activation which is not affected by pre-stimulation with IL-6. All these observations suggest that desensitization and inhibition of signalling are mechanistically distinct. PMID:14611646

Comparative characterization of stromal vascular cells derived from three types of vascular wall and adipose tissue.

PubMed

Yang, Santsun; Eto, Hitomi; Kato, Harunosuke; Doi, Kentaro; Kuno, Shinichiro; Kinoshita, Kahori; Ma, Hsu; Tsai, Chi-Han; Chou, Wan-Ting; Yoshimura, Kotaro

2013-12-01

Multipotent stem/progenitor cells localize perivascularly in many organs and vessel walls. These tissue-resident stem/progenitor cells differentiate into vascular endothelial cells, pericytes, and other mesenchymal lineages, and participate in physiological maintenance and repair of vasculatures. In this study, we characterized stromal vascular cells obtained through the explant culture method from three different vessel walls in humans: arterial wall (ART; >500 μm in diameter), venous wall (VN; >500 μm in diameter), and small vessels in adipose tissue (SV; arterioles and venules, <100 μm in diameter). These were examined for functionality and compared with adipose-derived stem/stromal cells (ASCs). All stromal vascular cells of different origins presented fibroblast-like morphology and we could not visually discriminate one population from another. Flow cytometry showed that the cultured population heterogeneously expressed a variety of surface antigens associated with stem/progenitor cells, but CD105 was expressed by most cells in all groups, suggesting that the cells generally shared the characteristics of mesenchymal stem cells. Our histological and flow cytometric data suggested that the main population of vessel wall-derived stromal vascular cells were CD34(+)/CD31(-) and came from the tunica adventitia and areola tissue surrounding the adventitia. CD271 (p75NTR) was expressed by the vasa vasorum in the VN adventitia and by a limited population in the adventitia of SV. All three populations differentiated into multiple lineages as did ASCs. ART cells induced the largest quantity of calcium formation in the osteogenic medium, whereas ASCs showed the greatest adipogenic differentiation. SV and VN stromal cells had greater potency for network formation than did ART stromal cells. In conclusion, the three stromal vascular populations exhibited differential functional properties. Our results have clinical implications for vascular diseases such as arterial wall calcification and possible applications to regenerative therapies involving each vessel wall-resident stromal population.

Discrimination of lichen genera and species using element concentrations

USGS Publications Warehouse

Bennett, James P.

2008-01-01

The importance of organic chemistry in the classification of lichens is well established, but inorganic chemistry has been largely overlooked. Six lichen species were studied over a period of 23 years that were growing in 11 protected areas of the northern Great Lakes ecoregion, which were not greatly influenced by anthropogenic particulates or gaseous air pollutants. The elemental data from these studies were aggregated in order to test the hypothesis that differences among species in tissue element concentrations were large enough to discriminate between taxa faithfully. Concentrations of 16 chemical elements that were found in tissue samples from Cladonia rangiferina, Evernia mesomorpha, Flavopunctelia flaventior, Hypogymnia physodes, Parmelia sulcata, and Punctelia rudecta were analyzed statistically using multivariate discriminant functions and CART analyses, as well as t-tests. Genera and species were clearly separated in element space, and elemental discriminant functions were able to classify 91-100 of the samples correctly into species. At the broadest level, a Zn concentration of 51 ppm in tissues of four of the lichen species effectively discriminated foliose from fruticose species. Similarly, a S concentration of 680 ppm discriminated C. rangiferina and E. mesomorpha, and a Ca concentration of 10 436 ppm discriminated H. physodes from P. sulcata. For the three parmelioid species, a Ca concentration >32 837 ppm discriminated Punctelia rudecta from the other two species, while a Zn concentration of 56 ppm discriminated Parmelia sulcata from F. flaventior. Foliose species also had higher concentrations than did fruticose species of all elements except Na. Elemental signatures for each of the six species were developed using standardized means. Twenty-four mechanisms explaining the differences among species are summarized. Finally, the relationships of four species based on element concentrations, using additive-trees clustering of a Euclidean-distance matrix, produced identical relationships as did analyses based on secondary product chemistry that used additive-trees clustering of a Jaccard similarity matrix. At least for these six species, element composition has taxonomic significance, and may be useful for discriminating other taxa.

Effects of nutritional status and cognitive ability on olfactory function in geriatric patients.

PubMed

Jin, Sung-Yong; Jeong, Hye Seon; Lee, Jin Woo; Kwon, Ki Ryun; Rha, Ki-Sang; Kim, Yong Min

2016-02-01

The aim of this study was to investigate the prevalence of olfactory dysfunction and evaluate the relationship between olfactory function and nutritional status, comorbidity, and the results of a neurocognitive test in geriatric patients who do not suffer from neurodegenerative disease. A total of 45 patients who visited the Geriatric Health Center of Chungnam National University Hospital were enrolled in this study. Olfactory function was assessed using a Korean Version of Sniffin' Stick Test II. Cognitive status of all participants was assessed with the MMSE-K (Korean version of the Mini-Mental State Examination). Nutritional status was assessed with body mass index, Mini-Nutritional Assessment (MNA), and serum total protein and albumin. A total of 45 participants were enrolled in this study. Of these subjects, 28 were men and 17 were women, with a mean age of 71.7±5.16 years. Nine (20%) were normosmia, 13 (28.9%) were hyposmia, and 23 (51.1%) were anosmia. Thirty-six patients (80%) suffered from olfactory dysfunction (anosmia or hyposmia). MMSE score showed significant correlation with MNA score. There were significant negative correlations between age and total TDI (threshold, discrimination, and identification) score, discrimination score, identification score, and MMSE score. MMSE score showed significant correlation with discrimination score and identification score. However, MNA score did not show any significant correlation with olfactory function test results. Although olfactory function was not influenced by nutritional status, abilities of discrimination and identification of odors were associated with cognitive function in geriatric patients. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Sensitive detection of point mutation using exponential strand displacement amplification-based surface enhanced Raman spectroscopy.

PubMed

Huang, Si-Qiang; Hu, Juan; Zhu, Guichi; Zhang, Chun-Yang

2015-03-15

Accurate identification of point mutation is particularly imperative in the field of biomedical research and clinical diagnosis. Here, we develop a sensitive and specific method for point mutation assay using exponential strand displacement amplification (SDA)-based surface enhanced Raman spectroscopy (SERS). In this method, a discriminating probe and a hairpin probe are designed to specifically recognize the sequence of human K-ras gene. In the presence of K-ras mutant target (C→T), the 3'-terminal of discriminating probe and the 5'-terminal of hairpin probe can be ligated to form a SDA template. Subsequently, the 3'-terminal of hairpin probe can function as a primer to initiate the SDA reaction, producing a large amount of triggers. The resultant triggers can further hybridize with the discriminating probes to initiate new rounds of SDA reaction, leading to an exponential amplification reaction. With the addition of capture probe-modified gold nanoparticles (AuNPs) and the Rox-labeled reporter probes, the amplified triggers can be assembled on the surface of AuNPs through the formation of sandwich hybrids of capture probe-trigger-reporter probe, generating a strong Raman signal. While in the presence of K-ras wild-type target (C), neither ligation nor SDA reaction can be initiated and no Raman signal is observed. The proposed method exhibits high sensitivity with a detection limit of 1.4pM and can accurately discriminate as low as 1% variant frequency from the mixture of mutant target and wild-type target. Importantly, this method can be further applied to analyze the mutant target in the spiked HEK293T cell lysate, holding great potential for genetic analysis and disease prognosis. Copyright © 2014 Elsevier B.V. All rights reserved.

Effects of X-ray radiation on complex visual discrimination learning and social recognition memory in rats.

PubMed

Davis, Catherine M; Roma, Peter G; Armour, Elwood; Gooden, Virginia L; Brady, Joseph V; Weed, Michael R; Hienz, Robert D

2014-01-01

The present report describes an animal model for examining the effects of radiation on a range of neurocognitive functions in rodents that are similar to a number of basic human cognitive functions. Fourteen male Long-Evans rats were trained to perform an automated intra-dimensional set shifting task that consisted of their learning a basic discrimination between two stimulus shapes followed by more complex discrimination stages (e.g., a discrimination reversal, a compound discrimination, a compound reversal, a new shape discrimination, and an intra-dimensional stimulus discrimination reversal). One group of rats was exposed to head-only X-ray radiation (2.3 Gy at a dose rate of 1.9 Gy/min), while a second group received a sham-radiation exposure using the same anesthesia protocol. The irradiated group responded less, had elevated numbers of omitted trials, increased errors, and greater response latencies compared to the sham-irradiated control group. Additionally, social odor recognition memory was tested after radiation exposure by assessing the degree to which rats explored wooden beads impregnated with either their own odors or with the odors of novel, unfamiliar rats; however, no significant effects of radiation on social odor recognition memory were observed. These data suggest that rodent tasks assessing higher-level human cognitive domains are useful in examining the effects of radiation on the CNS, and may be applicable in approximating CNS risks from radiation exposure in clinical populations receiving whole brain irradiation.

Effects of X-Ray Radiation on Complex Visual Discrimination Learning and Social Recognition Memory in Rats

PubMed Central

Davis, Catherine M.; Roma, Peter G.; Armour, Elwood; Gooden, Virginia L.; Brady, Joseph V.; Weed, Michael R.; Hienz, Robert D.

2014-01-01

The present report describes an animal model for examining the effects of radiation on a range of neurocognitive functions in rodents that are similar to a number of basic human cognitive functions. Fourteen male Long-Evans rats were trained to perform an automated intra-dimensional set shifting task that consisted of their learning a basic discrimination between two stimulus shapes followed by more complex discrimination stages (e.g., a discrimination reversal, a compound discrimination, a compound reversal, a new shape discrimination, and an intra-dimensional stimulus discrimination reversal). One group of rats was exposed to head-only X-ray radiation (2.3 Gy at a dose rate of 1.9 Gy/min), while a second group received a sham-radiation exposure using the same anesthesia protocol. The irradiated group responded less, had elevated numbers of omitted trials, increased errors, and greater response latencies compared to the sham-irradiated control group. Additionally, social odor recognition memory was tested after radiation exposure by assessing the degree to which rats explored wooden beads impregnated with either their own odors or with the odors of novel, unfamiliar rats; however, no significant effects of radiation on social odor recognition memory were observed. These data suggest that rodent tasks assessing higher-level human cognitive domains are useful in examining the effects of radiation on the CNS, and may be applicable in approximating CNS risks from radiation exposure in clinical populations receiving whole brain irradiation. PMID:25099152

MR1 antigen presentation to mucosal-associated invariant T cells was highly conserved in evolution

PubMed Central

Huang, Shouxiong; Martin, Emmanuel; Kim, Sojung; Yu, Lawrence; Soudais, Claire; Fremont, Daved H.; Lantz, Olivier; Hansen, Ted H.

2009-01-01

Several nonclassical major histocompatibilty antigens (class Ib molecules) have emerged as key players in the early immune response to pathogens or stress. Class Ib molecules activate subsets of T cells that mount effector responses before the adaptive immune system, and thus are called innate T cells. MR1 is a novel class Ib molecule with properties highly suggestive of its regulation of mucosal immunity. The Mr1 gene is evolutionarily conserved, is non-Mhc linked, and controls the development of mucosal-associated invariant T (MAIT) cells. MAIT cells preferentially reside in the gut, and their development is dependent on commensal microbiota. Although these properties suggest that MAIT cells function as innate T cells in the mucosa, this has been difficult to test, due to the (i) paucity of MAIT cells that display MR1-specific activation in vitro and (ii) lack of knowledge of whether or not MR1 presents antigen. Here we show that both mouse and human MAIT cells display a high level of cross-reactivity on mammalian MR1 orthologs, but with differences consistent with limited ligand discrimination. Furthermore, acid eluates from recombinant or cellular MR1 proteins enhance MAIT cell activation in an MR1-specific and cross-species manner. Our findings demonstrate that the presentation pathway of MR1 to MAIT cells is highly evolutionarily conserved. PMID:19416870

Sex determination of the Acadian Flycatcher using discriminant analysis

USGS Publications Warehouse

Wilson, R.R.

1999-01-01

I used five morphometric variables from 114 individuals captured in Arkansas to develop a discriminant model to predict the sex of Acadian Flycatchers (Empidonax virescens). Stepwise discriminant function analyses selected wing chord and tail length as the most parsimonious subset of variables for discriminating sex. This two-variable model correctly classified 80% of females and 97% of males used to develop the model. Validation of the model using 19 individuals from Louisiana and Virginia resulted in 100% correct classification of males and females. This model provides criteria for sexing monomorphic Acadian Flycatchers during the breeding season and possibly during the winter.

Escherichia coli identification and strain discrimination using nanosecond laser-induced breakdown spectroscopy

NASA Astrophysics Data System (ADS)

Diedrich, Jonathan; Rehse, Steven J.; Palchaudhuri, Sunil

2007-04-01

Three strains of Escherichia coli, one strain of environmental mold, and one strain of Candida albicans yeast have been analyzed by laser-induced breakdown spectroscopy using nanosecond laser pulses. All microorganisms were analyzed while still alive and with no sample preparation. Nineteen atomic and ionic emission lines have been identified in the spectrum, which is dominated by calcium, magnesium, and sodium. A discriminant function analysis has been used to discriminate between the biotypes and E. coli strains. This analysis showed efficient discrimination between laser-induced breakdown spectroscopy spectra from different strains of a single bacteria species.

Renal cell carcinoma primary cultures maintain genomic and phenotypic profile of parental tumor tissues.

PubMed

Cifola, Ingrid; Bianchi, Cristina; Mangano, Eleonora; Bombelli, Silvia; Frascati, Fabio; Fasoli, Ester; Ferrero, Stefano; Di Stefano, Vitalba; Zipeto, Maria A; Magni, Fulvio; Signorini, Stefano; Battaglia, Cristina; Perego, Roberto A

2011-06-13

Clear cell renal cell carcinoma (ccRCC) is characterized by recurrent copy number alterations (CNAs) and loss of heterozygosity (LOH), which may have potential diagnostic and prognostic applications. Here, we explored whether ccRCC primary cultures, established from surgical tumor specimens, maintain the DNA profile of parental tumor tissues allowing a more confident CNAs and LOH discrimination with respect to the original tissues. We established a collection of 9 phenotypically well-characterized ccRCC primary cell cultures. Using the Affymetrix SNP array technology, we performed the genome-wide copy number (CN) profiling of both cultures and corresponding tumor tissues. Global concordance for each culture/tissue pair was assayed evaluating the correlations between whole-genome CN profiles and SNP allelic calls. CN analysis was performed using the two CNAG v3.0 and Partek software, and comparing results returned by two different algorithms (Hidden Markov Model and Genomic Segmentation). A very good overlap between the CNAs of each culture and corresponding tissue was observed. The finding, reinforced by high whole-genome CN correlations and SNP call concordances, provided evidence that each culture was derived from its corresponding tissue and maintained the genomic alterations of parental tumor. In addition, primary culture DNA profile remained stable for at least 3 weeks, till to third passage. These cultures showed a greater cell homogeneity and enrichment in tumor component than original tissues, thus enabling a better discrimination of CNAs and LOH. Especially for hemizygous deletions, primary cultures presented more evident CN losses, typically accompanied by LOH; differently, in original tissues the intensity of these deletions was weaken by normal cell contamination and LOH calls were missed. ccRCC primary cultures are a reliable in vitro model, well-reproducing original tumor genetics and phenotype, potentially useful for future functional approaches aimed to study genes or pathways involved in ccRCC etiopathogenesis and to identify novel clinical markers or therapeutic targets. Moreover, SNP array technology proved to be a powerful tool to better define the cell composition and homogeneity of RCC primary cultures. © 2011 Cifola et al; licensee BioMed Central Ltd.

Executive function deficits in team sport athletes with a history of concussion revealed by a visual-auditory dual task paradigm.

PubMed

Tapper, Anthony; Gonzalez, Dave; Roy, Eric; Niechwiej-Szwedo, Ewa

2017-02-01

The purpose of this study was to examine executive functions in team sport athletes with and without a history of concussion. Executive functions comprise many cognitive processes including, working memory, attention and multi-tasking. Past research has shown that concussions cause difficulties in vestibular-visual and vestibular-auditory dual-tasking, however, visual-auditory tasks have been examined rarely. Twenty-nine intercollegiate varsity ice hockey athletes (age = 19.13, SD = 1.56; 15 females) performed an experimental dual-task paradigm that required simultaneously processing visual and auditory information. A brief interview, event description and self-report questionnaires were used to assign participants to each group (concussion, no-concussion). Eighteen athletes had a history of concussion and 11 had no concussion history. The two tests involved visuospatial working memory (i.e., Corsi block test) and auditory tone discrimination. Participants completed both tasks individually, then simultaneously. Two outcome variables were measured, Corsi block memory span and auditory tone discrimination accuracy. No differences were shown when each task was performed alone; however, athletes with a history of concussion had a significantly worse performance on the tone discrimination task in the dual-task condition. In conclusion, long-term deficits in executive functions were associated with a prior history of concussion when cognitive resources were stressed. Evaluations of executive functions and divided attention appear to be helpful in discriminating participants with and without a history concussion.

Olfactory discrimination predicts cognitive decline among community-dwelling older adults

PubMed Central

Sohrabi, H R; Bates, K A; Weinborn, M G; Johnston, A N B; Bahramian, A; Taddei, K; Laws, S M; Rodrigues, M; Morici, M; Howard, M; Martins, G; Mackay-Sim, A; Gandy, S E; Martins, R N

2012-01-01

The presence of olfactory dysfunction in individuals at higher risk of Alzheimer's disease has significant diagnostic and screening implications for preventive and ameliorative drug trials. Olfactory threshold, discrimination and identification can be reliably recorded in the early stages of neurodegenerative diseases. The current study has examined the ability of various olfactory functions in predicting cognitive decline in a community-dwelling sample. A group of 308 participants, aged 46–86 years old, were recruited for this study. After 3 years of follow-up, participants were divided into cognitively declined and non-declined groups based on their performance on a neuropsychological battery. Assessment of olfactory functions using the Sniffin' Sticks battery indicated that, contrary to previous findings, olfactory discrimination, but not olfactory identification, significantly predicted subsequent cognitive decline (odds ratio=0.869; P<0.05; 95% confidence interval=0.764−0.988). The current study findings confirm previously reported associations between olfactory and cognitive functions, and indicate that impairment in olfactory discrimination can predict future cognitive decline. These findings further our current understanding of the association between cognition and olfaction, and support olfactory assessment in screening those at higher risk of dementia. PMID:22832962

Olfactory discrimination predicts cognitive decline among community-dwelling older adults.

PubMed

Sohrabi, H R; Bates, K A; Weinborn, M G; Johnston, A N B; Bahramian, A; Taddei, K; Laws, S M; Rodrigues, M; Morici, M; Howard, M; Martins, G; Mackay-Sim, A; Gandy, S E; Martins, R N

2012-05-22

The presence of olfactory dysfunction in individuals at higher risk of Alzheimer's disease has significant diagnostic and screening implications for preventive and ameliorative drug trials. Olfactory threshold, discrimination and identification can be reliably recorded in the early stages of neurodegenerative diseases. The current study has examined the ability of various olfactory functions in predicting cognitive decline in a community-dwelling sample. A group of 308 participants, aged 46-86 years old, were recruited for this study. After 3 years of follow-up, participants were divided into cognitively declined and non-declined groups based on their performance on a neuropsychological battery. Assessment of olfactory functions using the Sniffin' Sticks battery indicated that, contrary to previous findings, olfactory discrimination, but not olfactory identification, significantly predicted subsequent cognitive decline (odds ratio = 0.869; P<0.05; 95% confidence interval = 0.764-0.988). The current study findings confirm previously reported associations between olfactory and cognitive functions, and indicate that impairment in olfactory discrimination can predict future cognitive decline. These findings further our current understanding of the association between cognition and olfaction, and support olfactory assessment in screening those at higher risk of dementia.

Splicing fidelity: DEAD/H-box ATPases as molecular clocks.

PubMed

Koodathingal, Prakash; Staley, Jonathan P

2013-07-01

The spliceosome discriminates against suboptimal substrates, both during assembly and catalysis, thereby enhancing specificity during pre-mRNA splicing. Central to such fidelity mechanisms are a conserved subset of the DEAD- and DEAH-box ATPases, which belong to a superfamily of proteins that mediate RNP rearrangements in almost all RNA-dependent processes in the cell. Through an investigation of the mechanisms contributing to the specificity of 5' splice site cleavage, two related reports, one from our lab and the other from the Cheng lab, have provided insights into fidelity mechanisms utilized by the spliceosome. In our work, we found evidence for a kinetic proofreading mechanism in splicing in which the DEAH-box ATPase Prp16 discriminates against substrates undergoing slow 5' splice site cleavage. Additionally, our study revealed that discriminated substrates are discarded through a general spliceosome disassembly pathway, mediated by another DEAH-box ATPase Prp43. In their work, Tseng et al. described the underlying molecular events through which Prp16 discriminates against a splicing substrate during 5' splice site cleavage. Here, we present a synthesis of these two studies and, additionally, provide the first biochemical evidence for discrimination of a suboptimal splicing substrate just prior to 5' splice site cleavage. Together, these findings support a general mechanism for a ubiquitous superfamily of ATPases in enhancing specificity during RNA-dependent processes in the cell.

The effect of convection on infrared detection by antennal warm cells in the bloodsucking bug Rhodnius prolixus.

PubMed

Tichy, Harald; Zopf, Lydia M

2015-04-01

Previous work revealed that bloodsucking bugs can discriminate between oscillating changes in infrared (IR) radiation and air temperature (T) using two types of warm cells located in peg-in-pit sensilla and tapered hairs (Zopf LM, Lazzari CR, Tichy H. J Neurophysiol 111: 1341-1349, 2014). These two stimuli are encoded and discriminated by the response quotient of the two warm cell types. IR radiation stimulates the warm cell in the peg-in-pit sensillum more strongly than that in the tapered hair. T stimuli evoke the reverse responses; they stimulate the latter more strongly than the former. In nature, IR and T cues are always present with certain radiation intensities and air temperatures, here referred to as background IR radiation and background T. In this article, we found that the response quotient permits the discrimination of IR and T oscillations even in the presence of different backgrounds. We show that the two warm cells respond well to IR oscillations if the background T operates by natural convection but poorly at forced convection, even if the background T is higher than at natural convection. Background IR radiation strongly affects the responses to T oscillations: the discharge rates of both warm cells are higher the higher the power of the IR background. We compared the warm cell responses with the T measured inside small model objects shaped like a cylinder, a cone, or a disc. The experiments indicate that passive thermal effects of the sense organs rather than intrinsic properties of the sensory cells are responsible for the observed results. Copyright © 2015 the American Physiological Society.

Joint recognition and discrimination in nonlinear feature space

NASA Astrophysics Data System (ADS)

Talukder, Ashit; Casasent, David P.

1997-09-01

A new general method for linear and nonlinear feature extraction is presented. It is novel since it provides both representation and discrimination while most other methods are concerned with only one of these issues. We call this approach the maximum representation and discrimination feature (MRDF) method and show that the Bayes classifier and the Karhunen- Loeve transform are special cases of it. We refer to our nonlinear feature extraction technique as nonlinear eigen- feature extraction. It is new since it has a closed-form solution and produces nonlinear decision surfaces with higher rank than do iterative methods. Results on synthetic databases are shown and compared with results from standard Fukunaga- Koontz transform and Fisher discriminant function methods. The method is also applied to an automated product inspection problem (discrimination) and to the classification and pose estimation of two similar objects (representation and discrimination).

Further Examination of Discriminated Functional Communication

ERIC Educational Resources Information Center

Leon, Yanerys; Hausman, Nicole L.; Kahng, SungWoo; Becraft, Jessica L.

2010-01-01

One child with developmental disabilities was taught to mand for attention by saying "excuse me." Treatment effects were extended to multiple training contexts by teaching the participant to attend to naturally occurring discriminative stimuli through differential reinforcement of communication during periods of the experimenter's nonbusy…

Genome-wide RNAi screening identifies protein damage as a regulator of osmoprotective gene expression.

PubMed

Lamitina, Todd; Huang, Chunyi George; Strange, Kevin

2006-08-08

The detection, stabilization, and repair of stress-induced damage are essential requirements for cellular life. All cells respond to osmotic stress-induced water loss with increased expression of genes that mediate accumulation of organic osmolytes, solutes that function as chemical chaperones and restore osmotic homeostasis. The signals and signaling mechanisms that regulate osmoprotective gene expression in animal cells are poorly understood. Here, we show that gpdh-1 and gpdh-2, genes that mediate the accumulation of the organic osmolyte glycerol, are essential for survival of the nematode Caenorhabditis elegans during osmotic stress. Expression of GFP driven by the gpdh-1 promoter (P(gpdh-1)::GFP) is detected only during hypertonic stress but is not induced by other stressors. Using P(gpdh-1)::GFP expression as a phenotype, we screened approximately 16,000 genes by RNAi feeding and identified 122 that cause constitutive activation of gpdh-1 expression and glycerol accumulation. Many of these genes function to regulate protein translation and cotranslational protein folding and to target and degrade denatured proteins, suggesting that the accumulation of misfolded proteins functions as a signal to activate osmoprotective gene expression and organic osmolyte accumulation in animal cells. Consistent with this hypothesis, 73% of these protein-homeostasis genes have been shown to slow age-dependent protein aggregation in C. elegans. Because diverse environmental stressors and numerous disease states result in protein misfolding, mechanisms must exist that discriminate between osmotically induced and other forms of stress-induced protein damage. Our findings provide a foundation for understanding how these damage-selectivity mechanisms function.

Genome-wide RNAi screening identifies protein damage as a regulator of osmoprotective gene expression

PubMed Central

Lamitina, Todd; Huang, Chunyi George; Strange, Kevin

2006-01-01

The detection, stabilization, and repair of stress-induced damage are essential requirements for cellular life. All cells respond to osmotic stress-induced water loss with increased expression of genes that mediate accumulation of organic osmolytes, solutes that function as chemical chaperones and restore osmotic homeostasis. The signals and signaling mechanisms that regulate osmoprotective gene expression in animal cells are poorly understood. Here, we show that gpdh-1 and gpdh-2, genes that mediate the accumulation of the organic osmolyte glycerol, are essential for survival of the nematode Caenorhabditis elegans during osmotic stress. Expression of GFP driven by the gpdh-1 promoter (Pgpdh-1::GFP) is detected only during hypertonic stress but is not induced by other stressors. Using Pgpdh-1::GFP expression as a phenotype, we screened ≈16,000 genes by RNAi feeding and identified 122 that cause constitutive activation of gpdh-1 expression and glycerol accumulation. Many of these genes function to regulate protein translation and cotranslational protein folding and to target and degrade denatured proteins, suggesting that the accumulation of misfolded proteins functions as a signal to activate osmoprotective gene expression and organic osmolyte accumulation in animal cells. Consistent with this hypothesis, 73% of these protein-homeostasis genes have been shown to slow age-dependent protein aggregation in C. elegans. Because diverse environmental stressors and numerous disease states result in protein misfolding, mechanisms must exist that discriminate between osmotically induced and other forms of stress-induced protein damage. Our findings provide a foundation for understanding how these damage-selectivity mechanisms function. PMID:16880390

Metabolic Profile of Oral Squamous Carcinoma Cell Lines Relies on a Higher Demand of Lipid Metabolism in Metastatic Cells

PubMed Central

Sant’Anna-Silva, Ana Carolina B.; Santos, Gilson C.; Campos, Samir P. Costa; Oliveira Gomes, André Marco; Pérez-Valencia, Juan Alberto; Rumjanek, Franklin David

2018-01-01

Tumor cells are subjected to a broad range of selective pressures. As a result of the imposed stress, subpopulations of surviving cells exhibit individual biochemical phenotypes that reflect metabolic reprograming. The present work aimed at investigating metabolic parameters of cells displaying increasing degrees of metastatic potential. The metabolites present in cell extracts fraction of tongue fibroblasts and of cell lines derived from human tongue squamous cell carcinoma lineages displaying increasing metastatic potential (SCC9 ZsG, LN1 and LN2) were analyzed by 1H NMR (nuclear magnetic resonance) spectroscopy. Living, intact cells were also examined by the non-invasive method of fluorescence lifetime imaging microscopy (FLIM) based on the auto fluorescence of endogenous NADH. The cell lines reproducibly exhibited distinct metabolic profiles confirmed by Partial Least-Square Discriminant Analysis (PLS-DA) of the spectra. Measurement of endogenous free and bound NAD(P)H relative concentrations in the intact cell lines showed that ZsG and LN1 cells displayed high heterogeneity in the energy metabolism, indicating that the cells would oscillate between glycolysis and oxidative metabolism depending on the microenvironment’s composition. However, LN2 cells appeared to have more contributions to the oxidative status, displaying a lower NAD(P)H free/bound ratio. Functional experiments of energy metabolism, mitochondrial physiology, and proliferation assays revealed that all lineages exhibited similar energy features, although resorting to different bioenergetics strategies to face metabolic demands. These differentiated functions may also promote metastasis. We propose that lipid metabolism is related to the increased invasiveness as a result of the accumulation of malonate, methyl malonic acid, n-acetyl and unsaturated fatty acids (CH2)n in parallel with the metastatic potential progression, thus suggesting that the NAD(P)H reflected the lipid catabolic/anabolic pathways. PMID:29456966

Investigating the Predictive Value of Functional MRI to Appetitive and Aversive Stimuli: A Pattern Classification Approach

PubMed Central

McCabe, Ciara; Rocha-Rego, Vanessa

2016-01-01

Background Dysfunctional neural responses to appetitive and aversive stimuli have been investigated as possible biomarkers for psychiatric disorders. However it is not clear to what degree these are separate processes across the brain or in fact overlapping systems. To help clarify this issue we used Gaussian process classifier (GPC) analysis to examine appetitive and aversive processing in the brain. Method 25 healthy controls underwent functional MRI whilst seeing pictures and receiving tastes of pleasant and unpleasant food. We applied GPCs to discriminate between the appetitive and aversive sights and tastes using functional activity patterns. Results The diagnostic accuracy of the GPC for the accuracy to discriminate appetitive taste from neutral condition was 86.5% (specificity = 81%, sensitivity = 92%, p = 0.001). If a participant experienced neutral taste stimuli the probability of correct classification was 92. The accuracy to discriminate aversive from neutral taste stimuli was 82.5% (specificity = 73%, sensitivity = 92%, p = 0.001) and appetitive from aversive taste stimuli was 73% (specificity = 77%, sensitivity = 69%, p = 0.001). In the sight modality, the accuracy to discriminate appetitive from neutral condition was 88.5% (specificity = 85%, sensitivity = 92%, p = 0.001), to discriminate aversive from neutral sight stimuli was 92% (specificity = 92%, sensitivity = 92%, p = 0.001), and to discriminate aversive from appetitive sight stimuli was 63.5% (specificity = 73%, sensitivity = 54%, p = 0.009). Conclusions Our results demonstrate the predictive value of neurofunctional data in discriminating emotional and neutral networks of activity in the healthy human brain. It would be of interest to use pattern recognition techniques and fMRI to examine network dysfunction in the processing of appetitive, aversive and neutral stimuli in psychiatric disorders. Especially where problems with reward and punishment processing have been implicated in the pathophysiology of the disorder. PMID:27870866

[Social exclusion and discrimination of chronically mentally ill people in the Lodz region].

PubMed

Rasmus, Paweł; Nowaczyńska, Ewa; Stetkiewicz-Lewandowicz, Agnieszka; Rasmus, Alicja; Sobów, Tomasz

2013-11-01

Mental crisis exerts a negative effect on somatic, psychological and social functioning of a mentally ill person. Mental disease is often accompanied by factors increasing the social exclusion and discrimination of patients. Another problem is deeply rooted stereotypes and prejudices functioning in the public opinion, according to which people who suffer from mental disorder are considered insane and often dangerous for society. In Poland, thanks to, amongst others, the ESF (The European Social Fund) funds, it is possible to finance and implement research concerning social exclusion and discrimination of people who have experienced a mental crisis. The aim of the study was to evaluate the level of social exclusion and discrimination of people suffering from mental disorders from the Lodz region on the basis of seven points scale assessing their personal, occupational, and social functioning. MATERIAL AND METHODS; The study included a group of 101 patients with mental disorders. Participants were selected randomly from mental health institutions from the region of Lodz. To evaluate the problem of social exclusion in the group of patients a interview questionnaire was used. Social exclusion concerned people suffering from schizophrenia and psychosis, more than six years of illness, those with allocated disability pension, non-working and non-learning, with the lowest levels of education and maintaining a one-person household or living with one parent. Those who experienced the lowest degree of social exclusion were mainly people suffering from mood disorders, people with higher education, learning and working, living with both parents. Groups experiencing discrimination were mostly people with schizophrenia, disorders due to psychoactive substances, those with secondary and professional education, patients having a certificate of disability and maintaining a one-person household. Social exclusion of mentally ill people was mainly related to their low education, civic, social and economic activity. The problem of discrimination concerned 17% of the tested group. Half of participants of the study did not experience the discrimination effect.

Unperturbed Cytotoxic Lymphocyte Phenotype and Function in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Patients

PubMed Central

Theorell, Jakob; Bileviciute-Ljungar, Indre; Tesi, Bianca; Schlums, Heinrich; Johnsgaard, Mette Sophie; Asadi-Azarbaijani, Babak; Bolle Strand, Elin; Bryceson, Yenan T.

2017-01-01

Myalgic encephalomyelitis or chronic fatigue syndrome (ME/CFS) is a debilitating disorder linked to diverse intracellular infections as well as physiological stress. Cytotoxic lymphocytes combat intracellular infections. Their function is attenuated by stress. Despite numerous studies, the role of cytotoxic lymphocytes in ME/CFS remains unclear. Prompted by advances in the understanding of defects in lymphocyte cytotoxicity, the discovery of adaptive natural killer (NK) cell subsets associated with certain viral infections, and compelling links between stress, adrenaline, and cytotoxic lymphocyte function, we reassessed the role of cytotoxic lymphocytes in ME/CFS. Forty-eight patients from two independent cohorts fulfilling the Canada 2003 criteria for ME/CFS were evaluated with respect to cytotoxic lymphocyte phenotype and function. Results were compared to values from matched healthy controls. Reproducible differences between patients and controls were not found in cytotoxic lymphocyte numbers, cytotoxic granule content, activation status, exocytotic capacity, target cell killing, or cytokine production. One patient expressed low levels of perforin, explained by homozygosity for the PRF1 p.A91V variant. However, overall, this variant was present in a heterozygous state at the expected population frequency among ME/CFS patients. No single patient displayed any pathological patterns of cellular responses. Increased expansions of adaptive NK cells or deviant cytotoxic lymphocyte adrenaline-mediated inhibition were not observed. In addition, supervised dimensionality reduction analyses of the full, multidimensional datasets did not reveal any reproducible patient/control discriminators. In summary, employing sensitive assays and analyses for quantification of cytotoxic lymphocyte differentiation and function, cytotoxicity lymphocyte aberrances were not found among ME/CFS patients. These assessments of cytotoxic lymphocytes therefore do not provide useful biomarkers for the diagnosis of ME/CFS. PMID:28694809

Ras and relatives--job sharing and networking keep an old family together.

PubMed

Ehrhardt, Annette; Ehrhardt, Götz R A; Guo, Xuecui; Schrader, John W

2002-10-01

Many members of the Ras superfamily of GTPases have been implicated in the regulation of hematopoietic cells, with roles in growth, survival, differentiation, cytokine production, chemotaxis, vesicle-trafficking, and phagocytosis. The well-known p21 Ras proteins H-Ras, N-Ras, K-Ras 4A, and K-Ras 4B are also frequently mutated in human cancer and leukemia. Besides the four p21 Ras proteins, the Ras subfamily of the Ras superfamily includes R-Ras, TC21 (R-Ras2), M-Ras (R-Ras3), Rap1A, Rap1B, Rap2A, Rap2B, RalA, and RalB. They exhibit remarkable overall amino acid identities, especially in the regions interacting with the guanine nucleotide exchange factors that catalyze their activation. In addition, there is considerable sharing of various downstream effectors through which they transmit signals and of GTPase activating proteins that downregulate their activity, resulting in overlap in their regulation and effector function. Relatively little is known about the physiological functions of individual Ras family members, although the presence of well-conserved orthologs in Caenorhabditis elegans suggests that their individual roles are both specific and vital. The structural and functional similarities have meant that commonly used research tools fail to discriminate between the different family members, and functions previously attributed to one family member may be shared with other members of the Ras family. Here we discuss similarities and differences in activation, effector usage, and functions of different members of the Ras subfamily. We also review the possibility that the differential localization of Ras proteins in different parts of the cell membrane may govern their responses to activation of cell surface receptors.

Two microRNA panels to discriminate three subtypes of lung carcinoma in bronchial brushing specimens.

PubMed

Huang, Wei; Hu, Jie; Yang, Da-wei; Fan, Xin-ting; Jin, Yi; Hou, Ying-yong; Wang, Ji-ping; Yuan, Yun-feng; Tan, Yun-shan; Zhu, Xiong-Zeng; Bai, Chun-xue; Wu, Ying; Zhu, Hong-guang; Lu, Shao-hua

2012-12-01

Effective treatment for lung cancer requires accuracy in subclassification of carcinoma subtypes. To identify microRNAs in bronchial brushing specimens for discriminating small cell lung cancer (SCLC) from non-small cell lung cancer (NSCLC) and for further differentiating squamous cell carcinoma (SQ) from adenocarcinoma (AC). Microarrays were used to screen 723 microRNAs in laser-captured, microdissected cancer cells from 82 snap-frozen surgical lung specimens. Quantitative reverse-transcriptase polymerase chain reaction was performed on 153 macrodissected formalin-fixed, paraffin-embedded (FFPE) surgical lung specimens to evaluate seven microRNA candidates discovered from microarrays. Two microRNA panels were constructed on the basis of a training cohort (n = 85) and validated using an independent cohort (n = 68). The microRNA panels were applied as differentiators of SCLC from NSCLC and of SQ from AC in 207 bronchial brushing specimens. Two microRNA panels yielded high diagnostic accuracy in discriminating SCLC from NSCLC (miR-29a and miR-375; area under the curve [AUC], 0.991 and 0.982 for training and validation data set, respectively) and in differentiating SQ from AC (miR-205 and miR-34a; AUC, 0.977 and 0.982 for training and validation data set, respectively) in FFPE surgical lung specimens. Moreover, the microRNA panels accurately differentiated SCLC from NSCLC (AUC, 0.947) and SQ from AC (AUC, 0.962) in bronchial brushing specimens. We found two microRNA panels that accurately discriminated between the three subtypes of lung carcinoma in bronchial brushing specimens. The identified microRNA panels may have considerable clinical value in differential diagnosis and optimizing treatment strategies based on lung cancer subtypes.

Neural mechanisms of coarse-to-fine discrimination in the visual cortex.

PubMed

Purushothaman, Gopathy; Chen, Xin; Yampolsky, Dmitry; Casagrande, Vivien A

2014-12-01

Vision is a dynamic process that refines the spatial scale of analysis over time, as evidenced by a progressive improvement in the ability to detect and discriminate finer details. To understand coarse-to-fine discrimination, we studied the dynamics of spatial frequency (SF) response using reverse correlation in the primary visual cortex (V1) of the primate. In a majority of V1 cells studied, preferred SF either increased monotonically with time (group 1) or changed nonmonotonically, with an initial increase followed by a decrease (group 2). Monotonic shift in preferred SF occurred with or without an early suppression at low SFs. Late suppression at high SFs always accompanied nonmonotonic SF dynamics. Bayesian analysis showed that SF discrimination performance and best discriminable SF frequencies changed with time in different ways in the two groups of neurons. In group 1 neurons, SF discrimination performance peaked on both left and right flanks of the SF tuning curve at about the same time. In group 2 neurons, peak discrimination occurred on the right flank (high SFs) later than on the left flank (low SFs). Group 2 neurons were also better discriminators of high SFs. We examined the relationship between the time at which SF discrimination performance peaked on either flank of the SF tuning curve and the corresponding best discriminable SFs in both neuronal groups. This analysis showed that the population best discriminable SF increased with time in V1. These results suggest neural mechanisms for coarse-to-fine discrimination behavior and that this process originates in V1 or earlier. Copyright © 2014 the American Physiological Society.

Parent Discrimination Predicts Mexican-American Adolescent Psychological Adjustment One Year Later

PubMed Central

Gonzales, Nancy A.; Fuligni, Andrew J.

2016-01-01

This study examined whether Mexican-American parent’s experiences with discrimination are related to adolescent psychological adjustment over time. The extent to which associations between parent discrimination and adolescent adjustment vary as a function of parent’s ethnic socialization of their children was also examined. Participants included 344 high school students from Mexican or Mexican-American backgrounds (primarily second generation; ages 14 – 16 at Wave 1) and their primary caregivers who completed surveys in a two-year longitudinal study. Results revealed that parent discrimination predicted internalizing symptoms and self-esteem among adolescents, one year later. Additionally, adolescents were more likely to report low self-esteem in relation to parents’ increased experiences of discrimination when parents conveyed ethnic socialization messages to them. PMID:27224903

Everyday Discrimination and Mood and Substance Use Disorders: A Latent Profile Analysis with African Americans and Caribbean Blacks

PubMed Central

Clark, Trenette T.; Salas-Wright, Christopher P.; Vaughn, Michael G.; Whitfield, Keith E.

2016-01-01

Perceived discrimination is a major source of health-related stress. The purpose of this study was to model the heterogeneity of everyday-discrimination experiences among African American and Caribbean Blacks and to identify differences in the prevalence of mood and substance use outcomes, including generalized anxiety disorder, major depressive disorder, alcohol-use disorder, and illicit drug-use disorder among the identified subgroups. The study uses data from the National Survey of American Life obtained from a sample of African American and Caribbean Black respondents (N = 4,462) between 18 and 65 years. We used latent profile analysis and multinomial regression analyses to identify and validate latent subgroups and test hypotheses, yielding 4 classes of perceived everyday discrimination: Low Discrimination, Disrespect and Condescension, General Discrimination, and Chronic Discrimination. Findings show significant differences exist between the Low Discrimination and General Discrimination classes for major depressive disorder, alcohol-use disorder, and illicit drug-use disorder. Moreover, we find significant differences exist between the Low Discrimination and Chronic Discrimination classes for the four disorders examined. Compared with the Chronic Discrimination class, members of the other classes were significantly less likely to meet criteria for generalized anxiety disorder, major depressive disorder, alcohol-use disorder, and illicit drug-use disorder. Findings suggest elevated levels of discrimination increase risk for mood and substance-use disorders. Importantly, results suggest the prevalence of mood and substance-use disorders is a function of the type and frequency of discrimination that individuals experience. PMID:25254321

Squamous epithelium formation in the respiratory intestine of the bronze Corydoras Corydoras aeneus (Callichthyidae Teleostei).

PubMed

Satora, Leszek; Kozioł, Katarzyna; Zebrowski, Jacek

2017-06-01

Accessory respiratory organs in fish exhibit great diversity but share the presence of numerous capillaries covered by a simple squamous epithelium. The adoption of the intestine for respiratory function needs certain special modifications. In this study, we explored immunohistochemical and metabolic fingerprint features that could underlay this adaptation in bronze corydoras Corydoras aeneus. Immunohistochemical localization of the cytoplasmic domain of epidermal growth factor receptor (EGFR) in the respiratory part of intestine demonstrated a strong positive immunoreaction in epithelial cells and connective tissue. Fourier Transfer Infrared (FTIR) spectroscopy coupled with chemometrics discriminated between anterior and posterior region of intestine in terms of secondary structure of proteins and the abundance of p-cresol and other phenolics. The latter were reduced in the posterior part of intestine, indicating the cessation of digestive function in this region. It has been suggested that aquatic hypoxia via endocrine cells (hypoxia-sensitive) activate EGFR, which induce proliferation of squamous epithelial cells, thereby enabling gas diffusion in the posterior part of intestine. It seems that hypoxia and normoxia are opposed conditions adjusting the production of squamous epithelial cells in this intestine. The physiological role of EGFR in the respiratory intestine of bronze corydoras is of interest not only from an evolutionary aspect but also in terms of a potential model for observations process proliferation squamous epithelial cells. Future investigations on the molecular responses to different water oxygen levels in air-breathing bronze corydoras fish are required to clarify the mechanism responsible for squamous cell proliferation. Copyright © 2017 Elsevier GmbH. All rights reserved.

Side population purified from hepatocellular carcinoma cells harbors cancer stem cell-like properties.

PubMed

Chiba, Tetsuhiro; Kita, Kaoru; Zheng, Yun-Wen; Yokosuka, Osamu; Saisho, Hiromitsu; Iwama, Atsushi; Nakauchi, Hiromitsu; Taniguchi, Hideki

2006-07-01

Recent advances in stem cell biology enable us to identify cancer stem cells in solid tumors as well as putative stem cells in normal solid organs. In this study, we applied side population (SP) cell analysis and sorting to established hepatocellular carcinoma (HCC) cell lines to detect subpopulations that function as cancer stem cells and to elucidate their roles in tumorigenesis. Among four cell lines analyzed, SP cells were detected in Huh7 (0.25%) and PLC/PRF/5 cells (0.80%), but not in HepG2 and Huh6 cells. SP cells demonstrated high proliferative potential and anti-apoptotic properties compared with those of non-SP cells. Immunocytochemistry examination showed that SP fractions contain a large number of cells presenting characteristics of both hepatocyte and cholangiocyte lineages. Non-obese diabetic/severe combined immunodeficiency (NOD/SCID) xenograft transplant experiments showed that only 1 x 10(3) SP cells were sufficient for tumor formation, whereas an injection of 1 x 10(6) non-SP cells did not initiate tumors. Re-analysis of SP cell-derived tumors showed that SP cells generated both SP and non-SP cells and tumor-initiating potential was maintained only in SP cells in serial transplantation. Microarray analysis discriminated a differential gene expression profile between SP and non-SP cells, and several so-called "stemness genes" were upregulated in SP cells in HCC cells. In conclusion, we propose that a minority population, detected as SP cells in HCC cells, possess extreme tumorigenic potential and provide heterogeneity to the cancer stem cell system characterized by distinct hierarchy.

Investigation of discriminant metabolites in tamoxifen-resistant and choline kinase-alpha-downregulated breast cancer cells using 1H-nuclear magnetic resonance spectroscopy.

PubMed

Kim, Hoe Suk; Tian, Lianji; Kim, Hyeonjin; Moon, Woo Kyung

2017-01-01

Metabolites linked to changes in choline kinase-α (CK-α) expression and drug resistance, which contribute to survival and autophagy mechanisms, are attractive targets for breast cancer therapies. We previously reported that autophagy played a causative role in driving tamoxifen (TAM) resistance of breast cancer cells (BCCs) and was also promoted by CK-α knockdown, resulting in the survival of TAM-resistant BCCs. There is no comparative study yet about the metabolites resulting from BCCs with TAM-resistance and CK-α knockdown. Therefore, the aim of this study was to explore the discriminant metabolic biomarkers responsible for TAM resistance as well as CK-α expression, which might be linked with autophagy through a protective role. A total of 33 intracellular metabolites, including a range of amino acids, energy metabolism-related molecules and others from cell extracts of the parental cells (MCF-7), TAM-resistant cells (MCF-7/TAM) and CK-α knockdown cells (MCF-7/shCK-α, MCF-7/TAM/shCK-α) were analyzed by proton nuclear magnetic resonance spectroscopy (1H-NMRS). Principal component analysis (PCA) and partial least square discriminant analysis (PLS-DA) revealed the existence of differences in the intracellular metabolites to separate the 4 groups: MCF-7 cells, MCF-7/TAM cells, MCF-7-shCK-α cells, and MCF-7/TAM/shCK-α cells. The metabolites with VIP>1 contributed most to the differentiation of the cell groups, and they included fumarate, UA (unknown A), lactate, myo-inositol, glycine, phosphocholine, UE (unknown E), glutamine, formate, and AXP (AMP/ADP/ATP). Our results suggest that these altered metabolites would be promising metabolic biomarkers for a targeted therapeutic strategy in BCCs that exhibit TAM-resistance and aberrant CK-α expression, which triggers a survival and drug resistance mechanism.

Sex estimation from the patella in an African American population.

PubMed

Peckmann, Tanya R; Fisher, Brooke

2018-02-01

The skull and pelvis have been used for the estimation of sex for unknown human remains. However, in forensic cases where skeletal remains often exhibit postmortem damage and taphonomic changes the patella may be used for the estimation of sex as it is a preservationally favoured bone. The goal of the present research was to derive discriminant function equations from the patella for estimation of sex from an historic African American population. Six parameters were measured on 200 individuals (100 males and 100 females), ranging in age from 20 to 80 years old, from the Robert J. Terry Anatomical Skeleton Collection. The statistical analyses showed that all variables were sexually dimorphic. Discriminant function score equations were generated for use in sex estimation. The overall accuracy of sex classification ranged from 80.0% to 85.0% for the direct method and 80.0%-84.5% for the stepwise method. Overall, when the Spanish and Black South African discriminant functions were applied to the African American population they showed low accuracy rates for sexing the African American sample. However, when the White South African discriminant functions were applied to the African American sample they displayed high accuracy rates for sexing the African American population. The patella was shown to be accurate for sex estimation in the historic African American population. Copyright © 2017 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.

Psychometric functions for pure-tone frequency discrimination.

PubMed

Dai, Huanping; Micheyl, Christophe

2011-07-01

The form of the psychometric function (PF) for auditory frequency discrimination is of theoretical interest and practical importance. In this study, PFs for pure-tone frequency discrimination were measured for several standard frequencies (200-8000 Hz) and levels [35-85 dB sound pressure level (SPL)] in normal-hearing listeners. The proportion-correct data were fitted using a cumulative-Gaussian function of the sensitivity index, d', computed as a power transformation of the frequency difference, Δf. The exponent of the power function corresponded to the slope of the PF on log(d')-log(Δf) coordinates. The influence of attentional lapses on PF-slope estimates was investigated. When attentional lapses were not taken into account, the estimated PF slopes on log(d')-log(Δf) coordinates were found to be significantly lower than 1, suggesting a nonlinear relationship between d' and Δf. However, when lapse rate was included as a free parameter in the fits, PF slopes were found not to differ significantly from 1, consistent with a linear relationship between d' and Δf. This was the case across the wide ranges of frequencies and levels tested in this study. Therefore, spectral and temporal models of frequency discrimination must account for a linear relationship between d' and Δf across a wide range of frequencies and levels. © 2011 Acoustical Society of America

The triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio as a predictor of β-cell function in African American women.

PubMed

Maturu, Amita; DeWitt, Peter; Kern, Philip A; Rasouli, Neda

2015-05-01

The TG/HDL-C ratio is used as a marker of insulin resistance (IR) in Caucasians. However, there are conflicting data on TG/HDL-C ratio as a predictor of IR in African Americans. Compared to Caucasians, African Americans have lower TG levels and increased insulin levels despite a greater risk for diabetes. We hypothesized that the TG/HDL-C ratio is predictive of IR and/or β-cell function in African American (AA) women. Non-diabetic AA women (n = 41) with a BMI > 25 kg/m(2) underwent frequently sampled intravenous glucose tolerance test (FSIGTT). Insulin sensitivity (SI) and the acute insulin response to glucose (AIRg) were measured using minimal model and β-cell function was determined by disposition index (DI = S I*AIRg). IR was defined as the lowest tertile of SI (<1.8 × 10(-4)min(-1)/μU/ml) and inadequate β cell compensation was defined as the lowest tertile of DI (< 900). Data were analyzed using logistic regression models and area under the receiver operating characteristic curve (AUC-ROC). An AUC-ROC > 0.70 was defined as significant discrimination. The mean (± SD) age was 38.5 ± 11.3 years, with BMI of 33.5 ± 6.7 kg/m(2) and fasting glucose of 86.5 ± 10.5 mg/dL. The AUC-ROC for the prediction of DI < 900 was 0.74 indicating that a higher TG/HDL-C ratio was associated with decreased DI. However, the AUC-ROC for prediction of IR or low AIRg (<335 μU/ml) was not significant. This study confirmed that the TG/HDL-C ratio is a poor predictor of IR in AA women. However, we did show an inverse association between the TG/HDL-C ratio and β-cell function, suggesting that this simple tool may effectively identify AA women at risk for DM2. Copyright © 2015 Elsevier Inc. All rights reserved.

Kin discrimination increases with genetic distance in a social amoeba.

PubMed

Ostrowski, Elizabeth A; Katoh, Mariko; Shaulsky, Gad; Queller, David C; Strassmann, Joan E

2008-11-25

In the social amoeba Dictyostelium discoideum, thousands of cells aggregate upon starvation to form a multicellular fruiting body, and approximately 20% of them die to form a stalk that benefits the others. The aggregative nature of multicellular development makes the cells vulnerable to exploitation by cheaters, and the potential for cheating is indeed high. Cells might avoid being victimized if they can discriminate among individuals and avoid those that are genetically different. We tested how widely social amoebae cooperate by mixing isolates from different localities that cover most of their natural range. We show here that different isolates partially exclude one another during aggregation, and there is a positive relationship between the extent of this exclusion and the genetic distance between strains. Our findings demonstrate that D. discoideum cells co-aggregate more with genetically similar than dissimilar individuals, suggesting the existence of a mechanism that discerns the degree of genetic similarity between individuals in this social microorganism.

Flow cytometry as a tool for analyzing changes in Plasmodium falciparum cell cycle following treatment with indol compounds.

PubMed

Schuck, Desirée Cigaran; Ribeiro, Ramira Yuri; Nery, Arthur A; Ulrich, Henning; Garcia, Célia R S

2011-11-01

Melatonin and its derivatives modulate the Plasmodium falciparum and Plasmodium chabaudi cell cycle. Flow cytometry was employed together with the nucleic acid dye YOYO-1 allowing precise discrimination between mono- and multinucleated forms of P. falciparum-infected red blood cell. The use of YOYO-1 permitted excellent discrimination between uninfected and infected red blood cells as well as between early and late parasite stages. Fluorescence intensities of schizont-stage parasites were about 10-fold greater than those of ring-trophozoite form parasites. Melatonin and related indolic compounds including serotonin, N-acetyl-serotonin and tryptamine induced an increase in the percentage of multinucleated forms compared to non-treated control cultures. YOYO-1 staining of infected erythrocyte and subsequent flow cytometry analysis provides a powerful tool in malaria research for screening of bioactive compounds. Copyright © 2011 International Society for Advancement of Cytometry.

Random search optimization based on genetic algorithm and discriminant function

NASA Technical Reports Server (NTRS)

Kiciman, M. O.; Akgul, M.; Erarslanoglu, G.

1990-01-01

The general problem of optimization with arbitrary merit and constraint functions, which could be convex, concave, monotonic, or non-monotonic, is treated using stochastic methods. To improve the efficiency of the random search methods, a genetic algorithm for the search phase and a discriminant function for the constraint-control phase were utilized. The validity of the technique is demonstrated by comparing the results to published test problem results. Numerical experimentation indicated that for cases where a quick near optimum solution is desired, a general, user-friendly optimization code can be developed without serious penalties in both total computer time and accuracy.

A model for food and stimulus changes that signal time-based contingency changes.

PubMed

Cowie, Sarah; Davison, Michael; Elliffe, Douglas

2014-11-01

When the availability of reinforcers depends on time since an event, time functions as a discriminative stimulus. Behavioral control by elapsed time is generally weak, but may be enhanced by added stimuli that act as additional time markers. The present paper assessed the effect of brief and continuous added stimuli on control by time-based changes in the reinforcer differential, using a procedure in which the local reinforcer ratio reversed at a fixed time after the most recent reinforcer delivery. Local choice was enhanced by the presentation of the brief stimuli, even when the stimulus change signalled only elapsed time, but not the local reinforcer ratio. The effect of the brief stimulus presentations on choice decreased as a function of time since the most recent stimulus change. We compared the ability of several versions of a model of local choice to describe these data. The data were best described by a model which assumed that error in discriminating the local reinforcer ratio arose from imprecise discrimination of reinforcers in both time and space, suggesting that timing behavior is controlled not only by discrimination elapsed time, but by discrimination of the reinforcer differential in time. © Society for the Experimental Analysis of Behavior.

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

Shumway, R.H.; McQuarrie, A.D.

Robust statistical approaches to the problem of discriminating between regional earthquakes and explosions are developed. We compare linear discriminant analysis using descriptive features like amplitude and spectral ratios with signal discrimination techniques using the original signal waveforms and spectral approximations to the log likelihood function. Robust information theoretic techniques are proposed and all methods are applied to 8 earthquakes and 8 mining explosions in Scandinavia and to an event from Novaya Zemlya of unknown origin. It is noted that signal discrimination approaches based on discrimination information and Renyi entropy perform better in the test sample than conventional methods based onmore » spectral ratios involving the P and S phases. Two techniques for identifying the ripple-firing pattern for typical mining explosions are proposed and shown to work well on simulated data and on several Scandinavian earthquakes and explosions. We use both cepstral analysis in the frequency domain and a time domain method based on the autocorrelation and partial autocorrelation functions. The proposed approach strips off underlying smooth spectral and seasonal spectral components corresponding to the echo pattern induced by two simple ripple-fired models. For two mining explosions, a pattern is identified whereas for two earthquakes, no pattern is evident.« less

Perceived discrimination, humiliation, and mental health: a mixed-methods study among Haitian migrants in the Dominican Republic.

PubMed

Keys, Hunter M; Kaiser, Bonnie N; Foster, Jennifer W; Burgos Minaya, Rosa Y; Kohrt, Brandon A

2015-01-01

Many Haitian migrants live and work as undocumented laborers in the Dominican Republic. This study examines the legacy of anti-Haitian discrimination in the Dominican Republic and association of discrimination with mental health among Haitian migrants. This study used mixed methods to generate hypotheses for associations between discrimination and mental health of Haitian migrants in the Dominican Republic. In-depth interviews were conducted with 21 Haitian and 18 Dominican community members and clinicians. One hundred and twenty-seven Haitian migrants participated in a pilot cross-sectional community survey. Instruments included culturally adapted Kreyòl versions of the Beck Depression Inventory (BDI) and Beck Anxiety Inventory (BAI) and a locally developed function impairment scale. Haitian migrants described humiliation (imilyasyon) as a reason for mental distress and barrier to health care. Dominicans reported that discrimination (discriminación) was not a current social problem and attributed negative social interactions to sociocultural, behavioral, and biological differences between Dominicans and Haitians. These qualitative findings were supported in the quantitative analyses. Perceived discrimination was significantly associated with depression severity and functional impairment. Perceived mistreatment by Dominicans was associated with a 6.6-point increase in BDI score (90% confidence interval [CI]: 3.29, 9.9). Knowing someone who was interrogated or deported was associated with a 3.4-point increase in BAI score (90% CI: 0.22, 6.64). Both qualitative and quantitative methods suggest that perceived discrimination and the experience of humiliation contribute to Haitian migrant mental ill-health and limit access to health care. Future research should evaluate these associations and identify intervention pathways for both improved treatment access and reduction of discrimination-related health risk factors.

Temporal discrimination, a cervical dystonia endophenotype: penetrance and functional correlates.

PubMed

Kimmich, Okka; Molloy, Anna; Whelan, Robert; Williams, Laura; Bradley, David; Balsters, Joshua; Molloy, Fiona; Lynch, Tim; Healy, Daniel G; Walsh, Cathal; O'Riordan, Seán; Reilly, Richard B; Hutchinson, Michael

2014-05-01

The pathogenesis of adult-onset primary dystonia remains poorly understood. There is variable age-related and gender-related expression of the phenotype, the commonest of which is cervical dystonia. Endophenotypes may provide insight into underlying genetic and pathophysiological mechanisms of dystonia. The temporal discrimination threshold (TDT)-the shortest time interval at which two separate stimuli can be detected as being asynchronous-is abnormal both in patients with cervical dystonia and in their unaffected first-degree relatives. Functional magnetic resonance imaging (fMRI) studies have shown that putaminal activation positively correlates with the ease of temporal discrimination between two stimuli in healthy individuals. We hypothesized that abnormal temporal discrimination would exhibit similar age-related and gender-related penetrance as cervical dystonia and that unaffected relatives with an abnormal TDT would have reduced putaminal activation during a temporal discrimination task. TDTs were examined in a group of 192 healthy controls and in 158 unaffected first-degree relatives of 84 patients with cervical dystonia. In 24 unaffected first-degree relatives, fMRI scanning was performed during a temporal discrimination task. The prevalence of abnormal TDTs in unaffected female relatives reached 50% after age 48 years; whereas, in male relatives, penetrance of the endophenotype was reduced. By fMRI, relatives who had abnormal TDTs, compared with relatives who had normal TDTs, had significantly less activation in the putamina and in the middle frontal and precentral gyri. Only the degree of reduction of putaminal activity correlated significantly with worsening of temporal discrimination. These findings further support abnormal temporal discrimination as an endophenotype of cervical dystonia involving disordered basal ganglia circuits. © 2014 International Parkinson and Movement Disorder Society.