Abnormal Facial Emotion Recognition in Depression: Serial Testing in an Ultra-Rapid-Cycling Patient.

ERIC Educational Resources Information Center

George, Mark S.; Huggins, Teresa; McDermut, Wilson; Parekh, Priti I.; Rubinow, David; Post, Robert M.

1998-01-01

Mood disorder subjects have a selective deficit in recognizing human facial emotion. Whether the facial emotion recognition errors persist during normal mood states (i.e., are state vs. trait dependent) was studied in one male bipolar II patient. Results of five sessions are presented and discussed. (Author/EMK)

Elements of Gender-Related Variability in the Selection of School Advisors in Greece

ERIC Educational Resources Information Center

Anastasiou, Sophia; Papakonstantinou, Georgios

2011-01-01

Purpose: In many countries, including Greece, women are underrepresented in school management positions. Modern societies recognize sex inequalities in management as a significant social problem and implement human resource policies intended to reduce such problems. The purpose of this paper is to assess the level of gender inequality in the…

Recognition of Naegleriae ameba surface protein epitopes by anti-human CD45 antibodies.

PubMed

Ravine, Terrence J; Polski, Jacek M; Jenkins, James

2010-04-01

Phagocytosis is a highly conserved mechanism exhibited by both free-living amebas and mammalian blood cells. Similarities demonstrated by either cell type during engulfment of the same bacterial species may imply analogous surface proteins involved in receptor-mediated endocytosis. The increased availability of anti-human leukocyte antibodies or clusters of differentiation (CD) markers used in conjunction with flow cytometric (FCM) and/or immunohistochemical (IHC) analysis provides investigators with a relatively easy method to screen different cell populations for comparable plasma membrane proteins. In this study, we incubated Naegleria and Acanthamoeba amebas with several directly conjugated anti-human leukocyte monoclonal antibodies (mAb) for similarly recognized amebic epitopes. CD marker selection was based upon a recognized role of each mAb in phagocyte activation and/or uptake of bacteria. These included CD14, CD45, and CD206. In FCM, only one CD45 antibody demonstrated strong reactivity with both Naegleria fowleri and Naegleria gruberi that was not expressed in similarly tested Acanthamoeba species. Additional testing of N. gruberi by IHC demonstrated reactivity to a different CD45 antibody. Our results suggest a possible utility of using anti-human leukocyte antibodies to screen amebic cells for similarly expressed protein epitopes. In doing so, several important items must be considered when selecting potential mAbs for testing to increase the probability of a positive result.

Digital Charge Coupled Device (CCD) Camera System Architecture

NASA Astrophysics Data System (ADS)

Babey, S. K.; Anger, C. D.; Green, B. D.

1987-03-01

We propose a modeling system for generic objects in order to recognize different objects from the same category with only one generic model. The representation consists of a prototype, represented by parts and their configuration. Parts are modeled by superquadric volumetric primitives which are combined via Boolean operations to form objects. Variations between objects within a category are described by allowable changes in structure and shape deformations of prototypical parts. Each prototypical part and relation has a set of associated features that can be recognized in the images. These features are used for selecting models from the model data base. The selected hypothetical models are then verified on the geometric level by deforming the prototype in allowable ways to match the data. We base our design of the modeling system upon the current psychological theories of categorization and of human visual perception.

Sexual orientation data collection and progress toward Healthy People 2010.

PubMed

Sell, R L; Becker, J B

2001-06-01

Without scientifically obtained data and published reports, it is difficult to raise awareness and acquire adequate resources to address the health concerns of lesbian, gay, and bisexual Americans. The Department of Health and Human Services must recognize gaps in its information systems regarding sexual orientation data and take immediate steps to monitor and eliminate health disparities as delineated in Healthy People 2010. A paper supported by funding from the Office of the Assistant Secretary for Planning and Evaluation explores these concerns and suggests that the department (1) create work groups to examine the collection of sexual orientation data; (2) create a set of guiding principles to govern the process of selecting standard definitions and measures; (3) recognize that racial/ethnic, immigrant-status, age, socioeconomic, and geographic differences must be taken into account when standard measures of sexual orientation are selected; (4) select a minimum set of standard sexual orientation measures; and (5) develop a long-range strategic plan for the collection of sexual orientation data.

Sexual orientation data collection and progress toward Healthy People 2010.

PubMed Central

Sell, R L; Becker, J B

2001-01-01

Without scientifically obtained data and published reports, it is difficult to raise awareness and acquire adequate resources to address the health concerns of lesbian, gay, and bisexual Americans. The Department of Health and Human Services must recognize gaps in its information systems regarding sexual orientation data and take immediate steps to monitor and eliminate health disparities as delineated in Healthy People 2010. A paper supported by funding from the Office of the Assistant Secretary for Planning and Evaluation explores these concerns and suggests that the department (1) create work groups to examine the collection of sexual orientation data; (2) create a set of guiding principles to govern the process of selecting standard definitions and measures; (3) recognize that racial/ethnic, immigrant-status, age, socioeconomic, and geographic differences must be taken into account when standard measures of sexual orientation are selected; (4) select a minimum set of standard sexual orientation measures; and (5) develop a long-range strategic plan for the collection of sexual orientation data. PMID:11392926

Influence of time and length size feature selections for human activity sequences recognition.

PubMed

Fang, Hongqing; Chen, Long; Srinivasan, Raghavendiran

2014-01-01

In this paper, Viterbi algorithm based on a hidden Markov model is applied to recognize activity sequences from observed sensors events. Alternative features selections of time feature values of sensors events and activity length size feature values are tested, respectively, and then the results of activity sequences recognition performances of Viterbi algorithm are evaluated. The results show that the selection of larger time feature values of sensor events and/or smaller activity length size feature values will generate relatively better results on the activity sequences recognition performances. © 2013 ISA Published by ISA All rights reserved.

Isolation of a human anti-epidermal growth factor receptor Fab antibody, EG-19-11, with subnanomolar affinity from naïve immunoglobulin repertoires using a hierarchical antibody library system.

PubMed

Hur, Byung-ung; Yoon, Jae-bong; Liu, Li-Kun; Cha, Sang-hoon

2010-11-30

Specific antibodies that possess a subnanomolar affinity are very difficult to obtain from human naïve immunoglobulin repertoires without the use of lengthy affinity optimization procedures. Here, we designed a hierarchical phage-displayed antibody library system to generate an enormous diversity of combinatorial Fab fragments (6×10(17)) and attempted to isolate high-affinity Fabs against the human epidermal growth factor receptor (EGFR). A primary antibody library, designated HuDVFab-8L, comprising 4.5×10(9) human naïve heavy chains and eight unspecified human naïve light chains was selected against the EGFR-Fc protein by biopanning, and four anti-EGFR Fab clones were isolated. Because one of the Fab clones, denoted EG-L2-11, recognized a native EGFR expressed on A431 cells, the heavy chain of the Fab was shuffled with a human naïve light chain repertoire with a diversity of 1.4×10(8) and selected a second time against the EGFR-Fc protein again. One EG-L2-11 variant, denoted EG-19-11, recognized an EGFR epitope that was almost the same as that bound by cetuximab and had a K(D) of approximately 540 pM for soluble EGFR, which is about 7-fold higher than that of the FabC225 derived from cetuximab. This variant was also internalized by A431 cells, likely via receptor-mediated endocytosis, and it efficiently inhibited EGF-mediated tyrosine phosphorylation of the EGFR. These results demonstrate that the use of our hierarchical antibody library system is advantageous in generating fully human antibodies especially with a therapeutic purpose. Copyright © 2010 Elsevier B.V. All rights reserved.

Phage display antibodies against ectromelia virus that neutralize variola virus: Selection and implementation for p35 neutralizing epitope mapping.

PubMed

Khlusevich, Yana; Matveev, Andrey; Baykov, Ivan; Bulychev, Leonid; Bormotov, Nikolai; Ilyichev, Ivan; Shevelev, Georgiy; Morozova, Vera; Pyshnyi, Dmitrii; Tikunova, Nina

2018-04-01

In this study, five phage display antibodies (pdAbs) against ectromelia virus (ECTV) were selected from vaccinia virus (VACV)-immune phage-display library of human single chain variable fragments (scFv). ELISA demonstrated that selected pdAbs could recognize ECTV, VACV, and cowpox virus (CPXV). Atomic force microscopy visualized binding of the pdAbs to VACV. Three of the selected pdAbs neutralized variola virus (VARV) in the plaque reduction neutralization test. Western blot analysis of ECTV, VARV, VACV, and CPXV proteins indicated that neutralizing pdAbs bound orthopoxvirus 35 kDa proteins, which are encoded by the open reading frames orthologous to the ORF H3L in VACV. The fully human antibody fh1A was constructed on the base of the VH and VL domains of pdAb, which demonstrated a dose-dependent inhibition of plaque formation after infection with VARV, VACV, and CPXV. To determine the p35 region responsible for binding to neutralizing pdAbs, a panel of truncated p35 proteins was designed and expressed in Escherichia coli cells, and a minimal p35 fragment recognized by selected neutralizing pdAbs was identified. In addition, peptide phage-display combinatorial libraries were applied to localize the epitope. The obtained data indicated that the epitope responsible for recognition by the neutralizing pdAbs is discontinuous and amino acid residues located within two p35 regions, 15-19 aa and 232-237 aa, are involved in binding with neutralizing anti-p35 antibodies. Copyright © 2018. Published by Elsevier B.V.

The sight of the peacock's tail makes me sick: the early arguments on sexual selection.

PubMed

Hiraiwa-Hasegawa, M

2000-03-01

Why does a peacock have a beautiful train, while a peahen is sober without such flamboyance? Darwin proposed the theory of sexual selection to explain the differences between the sexes of the same species. Recently the study of sexual selection has been one of the most flourishing areas in evolutionary biology. However, the theory met with great resistance from biologists since the publication of the idea and the history of the theory included a lot of misunderstanding and confusion. There are several reasons for this. First, classical Darwinism failed to recognize social competition as an important selective force. Second, the good-for-the-species argument, which persisted in the days after Darwin, made the sexual selection argument more difficult to under-stand. Compared to the discussions on animals, Darwin's argument on human sex differences is not satisfactory. The reason probably lies in the debate over human racial differences which prevailed in the 19th century.

CARbodies: Human Antibodies Against Cell Surface Tumor Antigens Selected From Repertoires Displayed on T Cell Chimeric Antigen Receptors

PubMed Central

Alonso-Camino, Vanesa; Sánchez-Martín, David; Compte, Marta; Nuñez-Prado, Natalia; Diaz, Rosa M; Vile, Richard; Alvarez-Vallina, Luis

2013-01-01

A human single-chain variable fragment (scFv) antibody library was expressed on the surface of human T cells after transduction with lentiviral vectors (LVs). The repertoire was fused to a first-generation T cell receptor ζ (TCRζ)-based chimeric antigen receptor (CAR). We used this library to isolate antibodies termed CARbodies that recognize antigens expressed on the tumor cell surface in a proof-of-principle system. After three rounds of activation-selection there was a clear repertoire restriction, with the emergence dominant clones. The CARbodies were purified from bacterial cultures as soluble and active proteins. Furthermore, to validate its potential application for adoptive cell therapy, human T cells were transduced with a LV encoding a second-generation costimulatory CAR (CARv2) bearing the selected CARbodies. Transduced human primary T cells expressed significant levels of the CARbodies-based CARv2 fusion protein on the cell surface, and importantly could be specifically activated, after stimulation with tumor cells. This approach is a promising tool for the generation of antibodies fully adapted to the display format (CAR) and the selection context (cell synapse), which could extend the scope of current adoptive cell therapy strategies with CAR-redirected T cells. PMID:23695536

"Orphan" retrogenes in the human genome.

PubMed

Ciomborowska, Joanna; Rosikiewicz, Wojciech; Szklarczyk, Damian; Makałowski, Wojciech; Makałowska, Izabela

2013-02-01

Gene duplicates generated via retroposition were long thought to be pseudogenized and consequently decayed. However, a significant number of these genes escaped their evolutionary destiny and evolved into functional genes. Despite multiple studies, the number of functional retrogenes in human and other genomes remains unclear. We performed a comparative analysis of human, chicken, and worm genomes to identify "orphan" retrogenes, that is, retrogenes that have replaced their progenitors. We located 25 such candidates in the human genome. All of these genes were previously known, and the majority has been intensively studied. Despite this, they have never been recognized as retrogenes. Analysis revealed that the phenomenon of replacing parental genes with their retrocopies has been taking place over the entire span of animal evolution. This process was often species specific and contributed to interspecies differences. Surprisingly, these retrogenes, which should evolve in a more relaxed mode, are subject to a very strong purifying selection, which is, on average, two and a half times stronger than other human genes. Also, for retrogenes, they do not show a typical overall tendency for a testis-specific expression. Notably, seven of them are associated with human diseases. Recognizing them as "orphan" retrocopies, which have different regulatory machinery than their parents, is important for any disease studies in model organisms, especially when discoveries made in one species are transferred to humans.

Marked differences in the antigenic structure of human respiratory syncytial virus F and G glycoproteins.

PubMed Central

García-Barreno, B; Palomo, C; Peñas, C; Delgado, T; Perez-Breña, P; Melero, J A

1989-01-01

Monoclonal antibodies directed against the glycoproteins of human respiratory syncytial virus were used in competitive enzyme-linked immunosorbent assays for topological mapping of epitopes. Whereas epitopes of the F glycoprotein could be ascribed to five nonoverlapping antigenic sites, anti-G antibodies recognized unique epitopes, many of whose competition profiles overlapped extensively. Variant viruses selected with a neutralizing (47F) anti-F antibody lost the binding for only 47F and 49F antibodies, which mapped in the same antigenic area. In contrast, viruses selected with an anti-G antibody lost the capacity to bind most of the anti-G antibodies, and their G protein was not recognized by an anti-virus antiserum, indicating major changes in the antigenic structure of the G molecule. Finally, we found great antigenic variation of the G protein among viral isolates. This occurred even within viruses of the same subtype with only limited divergence of amino acid sequence between strains. All of these data indicate marked differences in the antigenic organization of the G and F glycoproteins of respiratory syncytial virus; we discuss these differences in terms of the chemical structure of the glycoproteins. Images PMID:2463385

The Human Splicing Factor ASF/SF2 can Specifically Recognize Pre-mRNA 5' Splice Sites

NASA Astrophysics Data System (ADS)

Zuo, Ping; Manley, James L.

1994-04-01

ASF/SF2 is a human protein previously shown to function in in vitro pre-mRNA splicing as an essential factor necessary for all splices and also as an alternative splicing factor, capable of switching selection of 5' splice sites. To begin to study the protein's mechanism of action, we have investigated the RNA binding properties of purified recombinant ASF/SF2. Using UV crosslinking and gel shift assays, we demonstrate that the RNA binding region of ASF/SF2 can interact with RNA in a sequence-specific manner, recognizing the 5' splice site in each of two different pre-mRNAs. Point mutations in the 5' splice site consensus can reduce binding by as much as a factor of 100, with the largest effects observed in competition assays. These findings support a model in which ASF/SF2 aids in the recognition of pre-mRNA 5' splice sites.

Human Immunodeficiency Virus Proteins Mimic Human T Cell Receptors Inducing Cross-Reactive Antibodies

PubMed Central

2017-01-01

Human immunodeficiency virus (HIV) hides from the immune system in part by mimicking host antigens, including human leukocyte antigens. It is demonstrated here that HIV also mimics the V-β-D-J-β of approximately seventy percent of about 600 randomly selected human T cell receptors (TCR). This degree of mimicry is greater than any other human pathogen, commensal or symbiotic organism studied. These data suggest that HIV may be evolving into a commensal organism just as simian immunodeficiency virus has done in some types of monkeys. The gp120 envelope protein, Nef protein and Pol protein are particularly similar to host TCR, camouflaging HIV from the immune system and creating serious barriers to the development of safe HIV vaccines. One consequence of HIV mimicry of host TCR is that antibodies against HIV proteins have a significant probability of recognizing the corresponding TCR as antigenic targets, explaining the widespread observation of lymphocytotoxic autoantibodies in acquired immunodeficiency syndrome (AIDS). Quantitative enzyme-linked immunoadsorption assays (ELISA) demonstrated that every HIV antibody tested recognized at least one of twelve TCR, and as many as seven, with a binding constant in the 10−8 to 10−9 m range. HIV immunity also affects microbiome tolerance in ways that correlate with susceptibility to specific opportunistic infections. PMID:28972547

Identification of conformational epitopes for human IgG on Chemotaxis inhibitory protein of Staphylococcus aureus

PubMed Central

Gustafsson, Erika; Haas, Pieter-Jan; Walse, Björn; Hijnen, Marcel; Furebring, Christina; Ohlin, Mats; van Strijp, Jos AG; van Kessel, Kok PM

2009-01-01

Background The Chemotaxis inhibitory protein of Staphylococcus aureus (CHIPS) blocks the Complement fragment C5a receptor (C5aR) and formylated peptide receptor (FPR) and is thereby a potent inhibitor of neutrophil chemotaxis and activation of inflammatory responses. The majority of the healthy human population has antibodies against CHIPS that have been shown to interfere with its function in vitro. The aim of this study was to define potential epitopes for human antibodies on the CHIPS surface. We also initiate the process to identify a mutated CHIPS molecule that is not efficiently recognized by preformed anti-CHIPS antibodies and retains anti-inflammatory activity. Results In this paper, we panned peptide displaying phage libraries against a pool of CHIPS specific affinity-purified polyclonal human IgG. The selected peptides could be divided into two groups of sequences. The first group was the most dominant with 36 of the 48 sequenced clones represented. Binding to human affinity-purified IgG was verified by ELISA for a selection of peptide sequences in phage format. For further analysis, one peptide was chemically synthesized and antibodies affinity-purified on this peptide were found to bind the CHIPS molecule as studied by ELISA and Surface Plasmon Resonance. Furthermore, seven potential conformational epitopes responsible for antibody recognition were identified by mapping phage selected peptide sequences on the CHIPS surface as defined in the NMR structure of the recombinant CHIPS31–121 protein. Mapped epitopes were verified by in vitro mutational analysis of the CHIPS molecule. Single mutations introduced in the proposed antibody epitopes were shown to decrease antibody binding to CHIPS. The biological function in terms of C5aR signaling was studied by flow cytometry. A few mutations were shown to affect this biological function as well as the antibody binding. Conclusion Conformational epitopes recognized by human antibodies have been mapped on the CHIPS surface and amino acid residues involved in both antibody and C5aR interaction could be defined. This information has implications for the development of an effective anti-inflammatory agent based on a functional CHIPS molecule with low interaction with human IgG. PMID:19284584

Tetanus Neurotoxin Neutralizing Antibodies Screened from a Human Immune scFv Antibody Phage Display Library.

PubMed

Wang, Han; Yu, Rui; Fang, Ting; Yu, Ting; Chi, Xiangyang; Zhang, Xiaopeng; Liu, Shuling; Fu, Ling; Yu, Changming; Chen, Wei

2016-09-11

Tetanus neurotoxin (TeNT) produced by Clostridium tetani is one of the most poisonous protein substances. Neutralizing antibodies against TeNT can effectively prevent and cure toxicosis. Using purified Hc fragments of TeNT (TeNT-Hc) as an antigen, three specific neutralizing antibody clones recognizing different epitopes were selected from a human immune scFv antibody phage display library. The three antibodies (2-7G, 2-2D, and S-4-7H) can effectively inhibit the binding between TeNT-Hc and differentiated PC-12 cells in vitro. Moreover, 2-7G inhibited TeNT-Hc binding to the receptor via carbohydrate-binding sites of the W pocket while 2-2D and S-4-7H inhibited binding of the R pocket. Although no single mAb completely protected mice from the toxin, they could both prolong survival when challenged with 20 LD50s (50% of the lethal dose) of TeNT. When used together, the mAbs completely neutralized 1000 LD50s/mg Ab, indicating their high neutralizing potency in vivo. Antibodies recognizing different carbohydrate-binding pockets could have higher synergistic toxin neutralization activities than those that recognize the same pockets. These results could lead to further production of neutralizing antibody drugs against TeNT and indicate that using TeNT-Hc as an antigen for screening human antibodies for TeNT intoxication therapy from human immune antibody library was convenient and effective.

Heat shock protein 90-mediated peptide-selective presentation of cytosolic tumor antigen for direct recognition of tumors by CD4(+) T cells.

PubMed

Tsuji, Takemasa; Matsuzaki, Junko; Caballero, Otavia L; Jungbluth, Achim A; Ritter, Gerd; Odunsi, Kunle; Old, Lloyd J; Gnjatic, Sacha

2012-04-15

Tumor Ag-specific CD4(+) T cells play important functions in tumor immunosurveillance, and in certain cases they can directly recognize HLA class II-expressing tumor cells. However, the underlying mechanism of intracellular Ag presentation to CD4(+) T cells by tumor cells has not yet been well characterized. We analyzed two naturally occurring human CD4(+) T cell lines specific for different peptides from cytosolic tumor Ag NY-ESO-1. Whereas both lines had the same HLA restriction and a similar ability to recognize exogenous NY-ESO-1 protein, only one CD4(+) T cell line recognized NY-ESO-1(+) HLA class II-expressing melanoma cells. Modulation of Ag processing in melanoma cells using specific molecular inhibitors and small interfering RNA revealed a previously undescribed peptide-selective Ag-presentation pathway by HLA class II(+) melanoma cells. The presentation required both proteasome and endosomal protease-dependent processing mechanisms, as well as cytosolic heat shock protein 90-mediated chaperoning. Such tumor-specific pathway of endogenous HLA class II Ag presentation is expected to play an important role in immunosurveillance or immunosuppression mediated by various subsets of CD4(+) T cells at the tumor local site. Furthermore, targeted activation of tumor-recognizing CD4(+) T cells by vaccination or adoptive transfer could be a suitable strategy for enhancing the efficacy of tumor immunotherapy.

A rapid, generally applicable method to engineer zinc fingers illustrated by targeting the HIV-1 promoter.

PubMed

Isalan, M; Klug, A; Choo, Y

2001-07-01

DNA-binding domains with predetermined sequence specificity are engineered by selection of zinc finger modules using phage display, allowing the construction of customized transcription factors. Despite remarkable progress in this field, the available protein-engineering methods are deficient in many respects, thus hampering the applicability of the technique. Here we present a rapid and convenient method that can be used to design zinc finger proteins against a variety of DNA-binding sites. This is based on a pair of pre-made zinc finger phage-display libraries, which are used in parallel to select two DNA-binding domains each of which recognizes given 5 base pair sequences, and whose products are recombined to produce a single protein that recognizes a composite (9 base pair) site of predefined sequence. Engineering using this system can be completed in less than two weeks and yields proteins that bind sequence-specifically to DNA with Kd values in the nanomolar range. To illustrate the technique, we have selected seven different proteins to bind various regions of the human immunodeficiency virus 1 (HIV-1) promoter.

When does social learning become cultural learning?

PubMed

Heyes, Cecilia

2017-03-01

Developmental research on selective social learning, or 'social learning strategies', is currently a rich source of information about when children copy behaviour, and who they prefer to copy. It also has the potential to tell us when and how human social learning becomes cultural learning; i.e. mediated by psychological mechanisms that are specialized, genetically or culturally, to promote cultural inheritance. However, this review article argues that, to realize its potential, research on the development of selective social learning needs more clearly to distinguish functional from mechanistic explanation; to achieve integration with research on attention and learning in adult humans and 'dumb' animals; and to recognize that psychological mechanisms can be specialized, not only by genetic evolution, but also by associative learning and cultural evolution. © 2015 John Wiley & Sons Ltd.

High-throughput analysis of peptide binding modules

PubMed Central

Liu, Bernard A.; Engelmann, Brett; Nash, Piers D.

2014-01-01

Modular protein interaction domains that recognize linear peptide motifs are found in hundreds of proteins within the human genome. Some protein interaction domains such as SH2, 14-3-3, Chromo and Bromo domains serve to recognize post-translational modification of amino acids (such as phosphorylation, acetylation, methylation etc.) and translate these into discrete cellular responses. Other modules such as SH3 and PDZ domains recognize linear peptide epitopes and serve to organize protein complexes based on localization and regions of elevated concentration. In both cases, the ability to nucleate specific signaling complexes is in large part dependent on the selectivity of a given protein module for its cognate peptide ligand. High throughput analysis of peptide-binding domains by peptide or protein arrays, phage display, mass spectrometry or other HTP techniques provides new insight into the potential protein-protein interactions prescribed by individual or even whole families of modules. Systems level analyses have also promoted a deeper understanding of the underlying principles that govern selective protein-protein interactions and how selectivity evolves. Lastly, there is a growing appreciation for the limitations and potential pitfalls of high-throughput analysis of protein-peptide interactomes. This review will examine some of the common approaches utilized for large-scale studies of protein interaction domains and suggest a set of standards for the analysis and validation of datasets from large-scale studies of peptide-binding modules. We will also highlight how data from large-scale studies of modular interaction domain families can provide insight into systems level properties such as the linguistics of selective interactions. PMID:22610655

Software for Partly Automated Recognition of Targets

NASA Technical Reports Server (NTRS)

Opitz, David; Blundell, Stuart; Bain, William; Morris, Matthew; Carlson, Ian; Mangrich, Mark; Selinsky, T.

2002-01-01

The Feature Analyst is a computer program for assisted (partially automated) recognition of targets in images. This program was developed to accelerate the processing of high-resolution satellite image data for incorporation into geographic information systems (GIS). This program creates an advanced user interface that embeds proprietary machine-learning algorithms in commercial image-processing and GIS software. A human analyst provides samples of target features from multiple sets of data, then the software develops a data-fusion model that automatically extracts the remaining features from selected sets of data. The program thus leverages the natural ability of humans to recognize objects in complex scenes, without requiring the user to explain the human visual recognition process by means of lengthy software. Two major subprograms are the reactive agent and the thinking agent. The reactive agent strives to quickly learn the user's tendencies while the user is selecting targets and to increase the user's productivity by immediately suggesting the next set of pixels that the user may wish to select. The thinking agent utilizes all available resources, taking as much time as needed, to produce the most accurate autonomous feature-extraction model possible.

Discovery of tumor-specific irreversible inhibitors of stearoyl CoA desaturase | Office of Cancer Genomics

Cancer.gov

A hallmark of targeted cancer therapies is selective toxicity among cancer cell lines. We evaluated results from a viability screen of over 200,000 small molecules to identify two chemical series, oxalamides and benzothiazoles, that were selectively toxic at low nanomolar concentrations to the same 4 of 12 human lung cancer cell lines. Sensitive cell lines expressed cytochrome P450 (CYP) 4F11, which metabolized the compounds into irreversible inhibitors of stearoyl CoA desaturase (SCD). SCD is recognized as a promising biological target in cancer and metabolic disease.

Triple Helical Recognition of Pyrimidine Inversions in Polypurine Tracts of RNA by Nucleobase-modified PNA

PubMed Central

Gupta, Pankaj; Zengeya, Thomas; Rozners, Eriks

2013-01-01

Peptide nucleic acids containing 2-pyrimidinone (P) and 3-oxo-2,3-dihydropyridazine (E) heterocycles recognized C-G and U-A inversions in a polypurine tract of double helical RNA with high affinity and sequence selectivity at pH 6.25. E-modified PNA bound strongly to bacterial A-site RNA, while no binding was observed to the human A-site RNA. PMID:21909545

Odor source identification by grounding linguistic descriptions in an artificial nose

NASA Astrophysics Data System (ADS)

Loutfi, Amy; Coradeschi, Silvia; Duckett, Tom; Wide, Peter

2001-03-01

This paper addresses the problem of enabling autonomous agents (e.g., robots) to carry out human oriented tasks using an electronic nose. The nose consists of a combination of passive gas sensors with different selectivity, the outputs of which are fused together with an artificial neural network in order to recognize various human-determined odors. The basic idea is to ground human-provided linguistic descriptions of these odors in the actual sensory perceptions of the nose through a process of supervised learning. Analogous to the human nose, the paper explains a method by which an electronic nose can be used for substance identification. First, the receptors of the nose are exposed to a substance by means of inhalation with an electric pump. Then a chemical reaction takes place in the gas sensors over a period of time and an artificial neural network processes the resulting sensor patterns. This network was trained to recognize a basic set of pure substances such as vanilla, lavender and yogurt under controlled laboratory conditions. The complete system was then validated through a series of experiments on various combinations of the basic substances. First, we showed that the nose was able to consistently recognize unseen samples of the same substances on which it had been trained. In addition, we presented some first results where the nose was tested on novel combinations of substances on which it had not been trained by combining the learned descriptions - for example, it could distinguish lavender yogurt as a combination of lavender and yogurt.

[Brachycephaly in dog and cat: a "human induced" obstruction of the upper airways].

PubMed

Oechtering, G U; Schlüter, C; Lippert, J P

2010-07-01

Selective breeding for exaggerated features caused in many brachycephalic dog and cat breeds virtually a loss of the nose, with serious anatomical and functional consequences. In addition to respiratory and olfactory tasks, in dogs the nose is of vital importance for thermoregulation. As obligatory nose breathers, dogs suffer far more than humans when their nasal ventilation is restricted. An open discussion in the broad public has to motivate authorities and kennel clubs to recognize extreme brachycephalic breeding as seriously affecting animal health and welfare. Copyright Georg Thieme Verlag KG Stuttgart . New York.

Human resources and access to maternal health care.

PubMed

ten Hoope-Bender, P; Liljestrand, J; MacDonagh, S

2006-09-01

The lack of human resources is one of the main bottlenecks to achieving the Millennium Development Goals on maternal and child health. A coherent national policy, recognized across government, needs to be in place to overcome this especially in countries severely affected by HIV/AIDS. Such a policy should cover selection of pre-service students, the qualifications of trainers and training sites, supportive supervision, career path development, a package of carefully thought-out incentives for the retention of staff, strategies for interaction with communities, and an agreed-upon health staff HIV/AIDS policy. Without such coherent human resource planning, a large number of countries will fail to reduce maternal and newborn mortality.

Selection of suitable hand gestures for reliable myoelectric human computer interface.

PubMed

Castro, Maria Claudia F; Arjunan, Sridhar P; Kumar, Dinesh K

2015-04-09

Myoelectric controlled prosthetic hand requires machine based identification of hand gestures using surface electromyogram (sEMG) recorded from the forearm muscles. This study has observed that a sub-set of the hand gestures have to be selected for an accurate automated hand gesture recognition, and reports a method to select these gestures to maximize the sensitivity and specificity. Experiments were conducted where sEMG was recorded from the muscles of the forearm while subjects performed hand gestures and then was classified off-line. The performances of ten gestures were ranked using the proposed Positive-Negative Performance Measurement Index (PNM), generated by a series of confusion matrices. When using all the ten gestures, the sensitivity and specificity was 80.0% and 97.8%. After ranking the gestures using the PNM, six gestures were selected and these gave sensitivity and specificity greater than 95% (96.5% and 99.3%); Hand open, Hand close, Little finger flexion, Ring finger flexion, Middle finger flexion and Thumb flexion. This work has shown that reliable myoelectric based human computer interface systems require careful selection of the gestures that have to be recognized and without such selection, the reliability is poor.

Towards automated assistance for operating home medical devices.

PubMed

Gao, Zan; Detyniecki, Marcin; Chen, Ming-Yu; Wu, Wen; Hauptmann, Alexander G; Wactlar, Howard D

2010-01-01

To detect errors when subjects operate a home medical device, we observe them with multiple cameras. We then perform action recognition with a robust approach to recognize action information based on explicitly encoding motion information. This algorithm detects interest points and encodes not only their local appearance but also explicitly models local motion. Our goal is to recognize individual human actions in the operations of a home medical device to see if the patient has correctly performed the required actions in the prescribed sequence. Using a specific infusion pump as a test case, requiring 22 operation steps from 6 action classes, our best classifier selects high likelihood action estimates from 4 available cameras, to obtain an average class recognition rate of 69%.

An amorphous silicon photodiode microfluidic chip to detect nanomolar quantities of HIV-1 virion infectivity factor.

PubMed

Vistas, Cláudia R; Soares, Sandra S; Rodrigues, Rogério M M; Chu, Virginia; Conde, João P; Ferreira, Guilherme N M

2014-08-07

A hydrogenated amorphous silicon (a-Si:H) photosensor was explored for the quantitative detection of a HIV-1 virion infectivity factor (Vif) at a detection limit in the single nanomolar range. The a-Si:H photosensor was coupled with a microfluidic channel that was functionalized with a recombinant single chain variable fragment antibody. The biosensor selectively recognizes HIV-1 Vif from human cell extracts.

Oral streptococci utilize a Siglec-like domain of serine-rich repeat adhesins to preferentially target platelet sialoglycans in human blood.

PubMed

Deng, Lingquan; Bensing, Barbara A; Thamadilok, Supaporn; Yu, Hai; Lau, Kam; Chen, Xi; Ruhl, Stefan; Sullam, Paul M; Varki, Ajit

2014-12-01

Damaged cardiac valves attract blood-borne bacteria, and infective endocarditis is often caused by viridans group streptococci. While such bacteria use multiple adhesins to maintain their normal oral commensal state, recognition of platelet sialoglycans provides an intermediary for binding to damaged valvular endocardium. We use a customized sialoglycan microarray to explore the varied binding properties of phylogenetically related serine-rich repeat adhesins, the GspB, Hsa, and SrpA homologs from Streptococcus gordonii and Streptococcus sanguinis species, which belong to a highly conserved family of glycoproteins that contribute to virulence for a broad range of Gram-positive pathogens. Binding profiles of recombinant soluble homologs containing novel sialic acid-recognizing Siglec-like domains correlate well with binding of corresponding whole bacteria to arrays. These bacteria show multiple modes of glycan, protein, or divalent cation-dependent binding to synthetic glycoconjugates and isolated glycoproteins in vitro. However, endogenous asialoglycan-recognizing clearance receptors are known to ensure that only fully sialylated glycans dominate in the endovascular system, wherein we find these particular streptococci become primarily dependent on their Siglec-like adhesins for glycan-mediated recognition events. Remarkably, despite an excess of alternate sialoglycan ligands in cellular and soluble blood components, these adhesins selectively target intact bacteria to sialylated ligands on platelets, within human whole blood. These preferred interactions are inhibited by corresponding recombinant soluble adhesins, which also preferentially recognize platelets. Our data indicate that circulating platelets may act as inadvertent Trojan horse carriers of oral streptococci to the site of damaged endocardium, and provide an explanation why it is that among innumerable microbes that gain occasional access to the bloodstream, certain viridans group streptococci have a selective advantage in colonizing damaged cardiac valves and cause infective endocarditis.

Ensemble cryoEM elucidates the mechanism of insulin capture and degradation by human insulin degrading enzyme

PubMed Central

Bailey, Lucas J; Tan, Yong Zi; Wei, Hui; Wang, Andrew; Farcasanu, Mara; Woods, Virgil A; McCord, Lauren A; Lee, David; Shang, Weifeng; Deprez-Poulain, Rebecca; Deprez, Benoit; Liu, David R; Koide, Akiko; Koide, Shohei; Kossiakoff, Anthony A

2018-01-01

Insulin degrading enzyme (IDE) plays key roles in degrading peptides vital in type two diabetes, Alzheimer's, inflammation, and other human diseases. However, the process through which IDE recognizes peptides that tend to form amyloid fibrils remained unsolved. We used cryoEM to understand both the apo- and insulin-bound dimeric IDE states, revealing that IDE displays a large opening between the homologous ~55 kDa N- and C-terminal halves to allow selective substrate capture based on size and charge complementarity. We also used cryoEM, X-ray crystallography, SAXS, and HDX-MS to elucidate the molecular basis of how amyloidogenic peptides stabilize the disordered IDE catalytic cleft, thereby inducing selective degradation by substrate-assisted catalysis. Furthermore, our insulin-bound IDE structures explain how IDE processively degrades insulin by stochastically cutting either chain without breaking disulfide bonds. Together, our studies provide a mechanism for how IDE selectively degrades amyloidogenic peptides and offers structural insights for developing IDE-based therapies. PMID:29596046

Optimized Periocular Template Selection for Human Recognition

PubMed Central

Sa, Pankaj K.; Majhi, Banshidhar

2013-01-01

A novel approach for selecting a rectangular template around periocular region optimally potential for human recognition is proposed. A comparatively larger template of periocular image than the optimal one can be slightly more potent for recognition, but the larger template heavily slows down the biometric system by making feature extraction computationally intensive and increasing the database size. A smaller template, on the contrary, cannot yield desirable recognition though the smaller template performs faster due to low computation for feature extraction. These two contradictory objectives (namely, (a) to minimize the size of periocular template and (b) to maximize the recognition through the template) are aimed to be optimized through the proposed research. This paper proposes four different approaches for dynamic optimal template selection from periocular region. The proposed methods are tested on publicly available unconstrained UBIRISv2 and FERET databases and satisfactory results have been achieved. Thus obtained template can be used for recognition of individuals in an organization and can be generalized to recognize every citizen of a nation. PMID:23984370

Robust Indoor Human Activity Recognition Using Wireless Signals.

PubMed

Wang, Yi; Jiang, Xinli; Cao, Rongyu; Wang, Xiyang

2015-07-15

Wireless signals-based activity detection and recognition technology may be complementary to the existing vision-based methods, especially under the circumstance of occlusions, viewpoint change, complex background, lighting condition change, and so on. This paper explores the properties of the channel state information (CSI) of Wi-Fi signals, and presents a robust indoor daily human activity recognition framework with only one pair of transmission points (TP) and access points (AP). First of all, some indoor human actions are selected as primitive actions forming a training set. Then, an online filtering method is designed to make actions' CSI curves smooth and allow them to contain enough pattern information. Each primitive action pattern can be segmented from the outliers of its multi-input multi-output (MIMO) signals by a proposed segmentation method. Lastly, in online activities recognition, by selecting proper features and Support Vector Machine (SVM) based multi-classification, activities constituted by primitive actions can be recognized insensitive to the locations, orientations, and speeds.

Covariation between human pelvis shape, stature, and head size alleviates the obstetric dilemma

PubMed Central

Fischer, Barbara; Mitteroecker, Philipp

2015-01-01

Compared with other primates, childbirth is remarkably difficult in humans because the head of a human neonate is large relative to the birth-relevant dimensions of the maternal pelvis. It seems puzzling that females have not evolved wider pelvises despite the high maternal mortality and morbidity risk connected to childbirth. Despite this seeming lack of change in average pelvic morphology, we show that humans have evolved a complex link between pelvis shape, stature, and head circumference that was not recognized before. The identified covariance patterns contribute to ameliorate the “obstetric dilemma.” Females with a large head, who are likely to give birth to neonates with a large head, possess birth canals that are shaped to better accommodate large-headed neonates. Short females with an increased risk of cephalopelvic mismatch possess a rounder inlet, which is beneficial for obstetrics. We suggest that these covariances have evolved by the strong correlational selection resulting from childbirth. Although males are not subject to obstetric selection, they also show part of these association patterns, indicating a genetic–developmental origin of integration. PMID:25902498

Covariation between human pelvis shape, stature, and head size alleviates the obstetric dilemma.

PubMed

Fischer, Barbara; Mitteroecker, Philipp

2015-05-05

Compared with other primates, childbirth is remarkably difficult in humans because the head of a human neonate is large relative to the birth-relevant dimensions of the maternal pelvis. It seems puzzling that females have not evolved wider pelvises despite the high maternal mortality and morbidity risk connected to childbirth. Despite this seeming lack of change in average pelvic morphology, we show that humans have evolved a complex link between pelvis shape, stature, and head circumference that was not recognized before. The identified covariance patterns contribute to ameliorate the "obstetric dilemma." Females with a large head, who are likely to give birth to neonates with a large head, possess birth canals that are shaped to better accommodate large-headed neonates. Short females with an increased risk of cephalopelvic mismatch possess a rounder inlet, which is beneficial for obstetrics. We suggest that these covariances have evolved by the strong correlational selection resulting from childbirth. Although males are not subject to obstetric selection, they also show part of these association patterns, indicating a genetic-developmental origin of integration.

Explicit Encoding of Multimodal Percepts by Single Neurons in the Human Brain

PubMed Central

Quiroga, Rodrigo Quian; Kraskov, Alexander; Koch, Christof; Fried, Itzhak

2010-01-01

Summary Different pictures of Marilyn Monroe can evoke the same percept, even if greatly modified as in Andy Warhol’s famous portraits. But how does the brain recognize highly variable pictures as the same percept? Various studies have provided insights into how visual information is processed along the “ventral pathway,” via both single-cell recordings in monkeys [1, 2] and functional imaging in humans [3, 4]. Interestingly, in humans, the same “concept” of Marilyn Monroe can be evoked with other stimulus modalities, for instance by hearing or reading her name. Brain imaging studies have identified cortical areas selective to voices [5, 6] and visual word forms [7, 8]. However, how visual, text, and sound information can elicit a unique percept is still largely unknown. By using presentations of pictures and of spoken and written names, we show that (1) single neurons in the human medial temporal lobe (MTL) respond selectively to representations of the same individual across different sensory modalities; (2) the degree of multimodal invariance increases along the hierarchical structure within the MTL; and (3) such neuronal representations can be generated within less than a day or two. These results demonstrate that single neurons can encode percepts in an explicit, selective, and invariant manner, even if evoked by different sensory modalities. PMID:19631538

Weighted fusion of depth and inertial data to improve view invariance for real-time human action recognition

NASA Astrophysics Data System (ADS)

Chen, Chen; Hao, Huiyan; Jafari, Roozbeh; Kehtarnavaz, Nasser

2017-05-01

This paper presents an extension to our previously developed fusion framework [10] involving a depth camera and an inertial sensor in order to improve its view invariance aspect for real-time human action recognition applications. A computationally efficient view estimation based on skeleton joints is considered in order to select the most relevant depth training data when recognizing test samples. Two collaborative representation classifiers, one for depth features and one for inertial features, are appropriately weighted to generate a decision making probability. The experimental results applied to a multi-view human action dataset show that this weighted extension improves the recognition performance by about 5% over equally weighted fusion deployed in our previous fusion framework.

Neural Mechanisms of Recognizing Camouflaged Objects: A Human fMRI Study

DTIC Science & Technology

2015-07-30

Unlimited Final Report: Neural Mechanisms of Recognizing Camouflaged Objects: A Human fMRI Study The views, opinions and/or findings contained in this...27709-2211 Visual search, Camouflage, Functional magnetic resonance imaging ( fMRI ), Perceptual learning REPORT DOCUMENTATION PAGE 11. SPONSOR...ABSTRACT Number of Papers published in peer-reviewed journals: Final Report: Neural Mechanisms of Recognizing Camouflaged Objects: A Human fMRI Study

Integration trumps selection in object recognition.

PubMed

Saarela, Toni P; Landy, Michael S

2015-03-30

Finding and recognizing objects is a fundamental task of vision. Objects can be defined by several "cues" (color, luminance, texture, etc.), and humans can integrate sensory cues to improve detection and recognition [1-3]. Cortical mechanisms fuse information from multiple cues [4], and shape-selective neural mechanisms can display cue invariance by responding to a given shape independent of the visual cue defining it [5-8]. Selective attention, in contrast, improves recognition by isolating a subset of the visual information [9]. Humans can select single features (red or vertical) within a perceptual dimension (color or orientation), giving faster and more accurate responses to items having the attended feature [10, 11]. Attention elevates neural responses and sharpens neural tuning to the attended feature, as shown by studies in psychophysics and modeling [11, 12], imaging [13-16], and single-cell and neural population recordings [17, 18]. Besides single features, attention can select whole objects [19-21]. Objects are among the suggested "units" of attention because attention to a single feature of an object causes the selection of all of its features [19-21]. Here, we pit integration against attentional selection in object recognition. We find, first, that humans can integrate information near optimally from several perceptual dimensions (color, texture, luminance) to improve recognition. They cannot, however, isolate a single dimension even when the other dimensions provide task-irrelevant, potentially conflicting information. For object recognition, it appears that there is mandatory integration of information from multiple dimensions of visual experience. The advantage afforded by this integration, however, comes at the expense of attentional selection. Copyright © 2015 Elsevier Ltd. All rights reserved.

Selection on the human bitter taste gene, TAS2R16, in Eurasian populations.

PubMed

Li, Hui; Pakstis, Andrew J; Kidd, Judith R; Kidd, Kenneth K

2011-06-01

Bitter taste is one of the most important senses alerting humans to noxious foods. In gatherer communities, sensitivity to bitterness is presumably advantageous because of various noxious plants. TAS2R16 is the gene coding the taste receptor molecules for some of the most common toxins in plants. A previous study of this gene indicated selection has increased the frequency of a derived allele in this gene that arose before the human expansion out of Africa. We have applied a different methodology for detecting selection, the Long Range Haplotype (LRH) analysis, to TAS2R16 in a larger sampling of populations from around the world. The haplotype with the derived alleles at both the functional polymorphism and a polymorphism in the regulatory region of TAS2R16 showed evidence for recent positive selection in most of the Eurasian populations, though the highest selection signal occurs in Mbuti Pygmies, an African hunter-gatherer group. In Eurasia, only populations of Mesopotamia and the southeast coast of China have no signals of selection. The evidence of recent selection found in most Eurasian populations differs from the geographic pattern seen in the earlier study of selection. One can speculate that the difference may result from a gathering lifestyle extending into the most recent 10,000 yrs and the need to recognize newly encountered bitter natural toxins as populations expanded into new environments and the biota changes with the ending of the most recent ice age. Alternatively, the promoter region variant may be a marker for altered function beyond what the derived amino acid allele conferred.

Integration trumps selection in object recognition

PubMed Central

Saarela, Toni P.; Landy, Michael S.

2015-01-01

Summary Finding and recognizing objects is a fundamental task of vision. Objects can be defined by several “cues” (color, luminance, texture etc.), and humans can integrate sensory cues to improve detection and recognition [1–3]. Cortical mechanisms fuse information from multiple cues [4], and shape-selective neural mechanisms can display cue-invariance by responding to a given shape independent of the visual cue defining it [5–8]. Selective attention, in contrast, improves recognition by isolating a subset of the visual information [9]. Humans can select single features (red or vertical) within a perceptual dimension (color or orientation), giving faster and more accurate responses to items having the attended feature [10,11]. Attention elevates neural responses and sharpens neural tuning to the attended feature, as shown by studies in psychophysics and modeling [11,12], imaging [13–16], and single-cell and neural population recordings [17,18]. Besides single features, attention can select whole objects [19–21]. Objects are among the suggested “units” of attention because attention to a single feature of an object causes the selection of all of its features [19–21]. Here, we pit integration against attentional selection in object recognition. We find, first, that humans can integrate information near-optimally from several perceptual dimensions (color, texture, luminance) to improve recognition. They cannot, however, isolate a single dimension even when the other dimensions provide task-irrelevant, potentially conflicting information. For object recognition, it appears that there is mandatory integration of information from multiple dimensions of visual experience. The advantage afforded by this integration, however, comes at the expense of attentional selection. PMID:25802154

New Developments in Human Neurocognition: Clinical, Genetic and Brain Imaging Correlates of Impulsivity and Compulsivity

PubMed Central

Fineberg, Naomi A.; Chamberlain, Samuel R.; Goudriaan, Anna E.; Stein, Dan J.; Vanderschuren, Louk J.M.J.; Gillan, Claire M.; Shekar, Sameer; Gorwood, Philip A.P.M.; Voon, Valerie; Morein-Zamir, Sharon; Denys, Damiaan; Sahakian, Barbara J.; Moeller, F. Gerard; Robbins, Trevor W.; Potenza, Marc N.

2014-01-01

Impulsivity and compulsivity represent useful conceptualizations that involve dissociable cognitive functions, mediated by neuroanatomically and neurochemically distinct components of cortico-subcortical circuitry. The constructs were historically viewed as diametrically opposed, with impulsivity being associated with risk-seeking and compulsivity with harm-avoidance. However, they are increasingly recognized to be linked by shared neuropsychological mechanisms involving dysfunctional inhibition of thoughts and behaviors. In this paper, we selectively review new developments in the investigation of the neurocognition of impulsivity and compulsivity in humans, in order to advance our understanding of the pathophysiology of impulsive, compulsive and addictive disorders and indicate new directions for research. PMID:24512640

New developments in human neurocognition: clinical, genetic, and brain imaging correlates of impulsivity and compulsivity.

PubMed

Fineberg, Naomi A; Chamberlain, Samuel R; Goudriaan, Anna E; Stein, Dan J; Vanderschuren, Louk J M J; Gillan, Claire M; Shekar, Sameer; Gorwood, Philip A P M; Voon, Valerie; Morein-Zamir, Sharon; Denys, Damiaan; Sahakian, Barbara J; Moeller, F Gerard; Robbins, Trevor W; Potenza, Marc N

2014-02-01

Impulsivity and compulsivity represent useful conceptualizations that involve dissociable cognitive functions, which are mediated by neuroanatomically and neurochemically distinct components of cortico-subcortical circuitry. The constructs were historically viewed as diametrically opposed, with impulsivity being associated with risk-seeking and compulsivity with harm-avoidance. However, they are increasingly recognized to be linked by shared neuropsychological mechanisms involving dysfunctional inhibition of thoughts and behaviors. In this article, we selectively review new developments in the investigation of the neurocognition of impulsivity and compulsivity in humans, in order to advance our understanding of the pathophysiology of impulsive, compulsive, and addictive disorders and indicate new directions for research.

Software for Partly Automated Recognition of Targets

NASA Technical Reports Server (NTRS)

Opitz, David; Blundell, Stuart; Bain, William; Morris, Matthew; Carlson, Ian; Mangrich, Mark

2003-01-01

The Feature Analyst is a computer program for assisted (partially automated) recognition of targets in images. This program was developed to accelerate the processing of high-resolution satellite image data for incorporation into geographic information systems (GIS). This program creates an advanced user interface that embeds proprietary machine-learning algorithms in commercial image-processing and GIS software. A human analyst provides samples of target features from multiple sets of data, then the software develops a data-fusion model that automatically extracts the remaining features from selected sets of data. The program thus leverages the natural ability of humans to recognize objects in complex scenes, without requiring the user to explain the human visual recognition process by means of lengthy software. Two major subprograms are the reactive agent and the thinking agent. The reactive agent strives to quickly learn the user s tendencies while the user is selecting targets and to increase the user s productivity by immediately suggesting the next set of pixels that the user may wish to select. The thinking agent utilizes all available resources, taking as much time as needed, to produce the most accurate autonomous feature-extraction model possible.

Plants and geographical names in Croatia.

PubMed

Cargonja, Hrvoje; Daković, Branko; Alegro, Antun

2008-09-01

The main purpose of this paper is to present some general observations, regularities and insights into a complex relationship between plants and people through symbolic systems like geographical names on the territory of Croatia. The basic sources of data for this research were maps from atlas of Croatia of the scale 1:100000. Five groups of maps or areas were selected in order to represent main Croatian phytogeographic regions. A selection of toponyms from each of the map was made in which the name for a plant in Croatian language was recognized (phytotoponyms). Results showed that of all plant names recognized in geographical names the most represented are trees, and among them birch and oak the most. Furthermore, an attempt was made to explain the presence of the most represented plant species in the phytotoponyms in the light of general phytogeographical and sociocultural differences and similarities of comparing areas. The findings confirm an expectation that the genera of climazonal vegetation of particular area are the most represented among the phytotoponyms. Nevertheless, there are ample examples where representation of a plant name in the names of human environment can only be ascribed to ethno-linguistic and socio-cultural motives. Despite the reductionist character of applied methodology, this research also points out some advantages of this approach for ethnobotanic and ethnolinguistic studies of greater areas of human environment.

Neural network system and methods for analysis of organic materials and structures using spectral data

DOEpatents

Meyer, Bernd J.; Sellers, Jeffrey P.; Thomsen, Jan U.

1993-01-01

Apparatus and processes for recognizing and identifying materials. Characteristic spectra are obtained for the materials via spectroscopy techniques including nuclear magnetic resonance spectroscopy, infrared absorption analysis, x-ray analysis, mass spectroscopy and gas chromatography. Desired portions of the spectra may be selected and then placed in proper form and format for presentation to a number of input layer neurons in an offline neural network. The network is first trained according to a predetermined training process; it may then be employed to identify particular materials. Such apparatus and processes are particularly useful for recognizing and identifying organic compounds such as complex carbohydrates, whose spectra conventionally require a high level of training and many hours of hard work to identify, and are frequently indistinguishable from one another by human interpretation.

Invited commentary: Physical activity, mortality, and genetics.

PubMed

Rankinen, Tuomo; Bouchard, Claude

2007-08-01

The importance of regular physical activity to human health has been recognized for a long time, and a physically active lifestyle is now defined as a major component of public health policies. The independent contribution of regular physical activity to lower morbidity and mortality rates is generally accepted, and the biologic mechanisms mediating these health effects are actively investigated. A few years ago, data from the Finnish Twin Registry suggested that genetic selection may account for some of the physical-activity-related benefits on mortality rates. However, results from the Swedish Twin Registry study reported by Carlsson et al. in the current issue of the Journal (Am J Epidemiol 2007;166:255-259) do not support the genetic selection hypothesis. In this commentary, the authors review the nature of the associations among physical activity level, fitness, and longevity, with special reference to the role of human genetic variation, and discuss potential reasons for different outcomes of these large twin studies.

Mouse Regenerating Myofibers Detected as False-Positive Donor Myofibers with Anti-Human Spectrin

PubMed Central

Rozkalne, Anete; Adkin, Carl; Meng, Jinhong; Lapan, Ariya; Morgan, Jennifer E.

2014-01-01

Abstract Stem cell transplantation is being tested as a potential therapy for a number of diseases. Stem cells isolated directly from tissue specimens or generated via reprogramming of differentiated cells require rigorous testing for both safety and efficacy in preclinical models. The availability of mice with immune-deficient background that carry additional mutations in specific genes facilitates testing the efficacy of cell transplantation in disease models. The muscular dystrophies are a heterogeneous group of disorders, of which Duchenne muscular dystrophy is the most severe and common type. Cell-based therapy for muscular dystrophy has been under investigation for several decades, with a wide selection of cell types being studied, including tissue-specific stem cells and reprogrammed stem cells. Several immune-deficient mouse models of muscular dystrophy have been generated, in which human cells obtained from various sources are injected to assess their preclinical potential. After transplantation, the presence of engrafted human cells is detected via immunofluorescence staining, using antibodies that recognize human, but not mouse, proteins. Here we show that one antibody specific to human spectrin, which is commonly used to evaluate the efficacy of transplanted human cells in mouse muscle, detects myofibers in muscles of NOD/Rag1nullmdx5cv, NOD/LtSz-scid IL2Rγnull mice, or mdx nude mice, irrespective of whether they were injected with human cells. These “reactive” clusters are regenerating myofibers, which are normally present in dystrophic tissue and the spectrin antibody is likely recognizing utrophin, which contains spectrin-like repeats. Therefore, caution should be used in interpreting data based on detection of single human-specific proteins, and evaluation of human stem cell engraftment should be performed using multiple human-specific labeling strategies. PMID:24152287

Facial detection using deep learning

NASA Astrophysics Data System (ADS)

Sharma, Manik; Anuradha, J.; Manne, H. K.; Kashyap, G. S. C.

2017-11-01

In the recent past, we have observed that Facebook has developed an uncanny ability to recognize people in photographs. Previously, we had to tag people in photos by clicking on them and typing their name. Now as soon as we upload a photo, Facebook tags everyone on its own. Facebook can recognize faces with 98% accuracy which is pretty much as good as humans can do. This technology is called Face Detection. Face detection is a popular topic in biometrics. We have surveillance cameras in public places for video capture as well as security purposes. The main advantages of this algorithm over other are uniqueness and approval. We need speed and accuracy to identify. But face detection is really a series of several related problems: First, look at a picture and find all the faces in it. Second, focus on each face and understand that even if a face is turned in a weird direction or in bad lighting, it is still the same person. Third select features which can be used to identify each face uniquely like size of the eyes, face etc. Finally, compare these features to data we have to find the person name. As a human, your brain is wired to do all of this automatically and instantly. In fact, humans are too good at recognizing faces. Computers are not capable of this kind of high-level generalization, so we must teach them how to do each step in this process separately. The growth of face detection is largely driven by growing applications such as credit card verification, surveillance video images, authentication for banking and security system access.

HIV-1 Vaccines Based on Antibody Identification, B Cell Ontogeny, and Epitope Structure.

PubMed

Kwong, Peter D; Mascola, John R

2018-05-15

HIV-1 vaccine development has been stymied by an inability to induce broadly reactive neutralizing antibodies to the envelope (Env) trimer, the sole viral antigen on the virion surface. Antibodies isolated from HIV-1-infected donors, however, have been shown to recognize all major exposed regions of the prefusion-closed Env trimer, and an emerging understanding of the immunological and structural characteristics of these antibodies and the epitopes they recognize is enabling new approaches to vaccine design. Antibody lineage-based design creates immunogens that activate the naive ancestor-B cell of a target antibody lineage and that mature intermediate-B cells toward effective neutralization, with proof of principle achieved with select HIV-1-neutralizing antibody lineages in human-gene knock-in mouse models. Epitope-based vaccine design involves the engineering of sites of Env vulnerability as defined by the recognition of broadly neutralizing antibodies, with cross-reactive neutralizing antibodies elicited in animal models. Both epitope-based and antibody lineage-based HIV-1 vaccine approaches are being readied for human clinical trials. Published by Elsevier Inc.

The selective recognition of antibody IgY for digestive system cancers.

PubMed

Yang, J; Jin, Z; Yu, Q; Yang, T; Wang, H; Liu, L

1997-01-01

Biological methods for cancer therapies are very important. A small and efficient target carrier is the key component for anti-cancer drugs. In our laboratory, the antibody IgY was extracted from egg yolk of a SPF hen. The SPF hen was immunized with an antigene of P110 protein which was purified from human stomach cancer MGC-803 cells. Results indicated that the antibody IgY can specifically recognize gastrointestinal system cancers. It may become an important carrier for antitumorigenic drugs.

Schistosoma mansoni Infection of Mice, Rats and Humans Elicits a Strong Antibody Response to a Limited Number of Reduction-Sensitive Epitopes on Five Major Tegumental Membrane Proteins

PubMed Central

Tremblay, Jacqueline M.; Oliveira, Sergio C.; Da’dara, Akram A.; Skelly, Patrick J.

2017-01-01

Schistosomiasis is a major disease of the developing world for which no vaccine has been successfully commercialized. While numerous Schistosoma mansoni worm antigens have been identified that elicit antibody responses during natural infections, little is known as to the identities of the schistosome antigens that are most prominently recognized by antibodies generated through natural infection. Non-reducing western blots probed with serum from schistosome-infected mice, rats and humans on total extracts of larval or adult schistosomes revealed that a small number of antigen bands predominate in all cases. Recognition of each of these major bands was lost when the blots were run under reducing condition. We expressed a rationally selected group of schistosome tegumental membrane antigens in insect host cells, and used the membrane extracts of these cells to unambiguously identify the major antigens recognized by S. mansoni infected mouse, rat and human serum. These results revealed that a limited number of dominant, reduction-sensitive conformational epitopes on five major tegumental surface membrane proteins: SmTsp2, Sm23, Sm29, SmLy6B and SmLy6F, are primary targets of mouse, rat and human S. mansoni infection sera antibodies. We conclude that, Schistosoma mansoni infection of both permissive (mouse) and non-permissive (rat) rodent models, as well as humans, elicit a dominant antibody response recognizing a limited number of conformational epitopes on the same five tegumental membrane proteins. Thus it appears that neither infecting schistosomula nor mature adult schistosomes are substantively impacted by the robust circulating anti-tegumental antibody response they elicit to these antigens. Importantly, our data suggest a need to re-evaluate host immune responses to many schistosome antigens and has important implications regarding schistosome immune evasion mechanisms and schistosomiasis vaccine development. PMID:28095417

Image statistics underlying natural texture selectivity of neurons in macaque V4

PubMed Central

Okazawa, Gouki; Tajima, Satohiro; Komatsu, Hidehiko

2015-01-01

Our daily visual experiences are inevitably linked to recognizing the rich variety of textures. However, how the brain encodes and differentiates a plethora of natural textures remains poorly understood. Here, we show that many neurons in macaque V4 selectively encode sparse combinations of higher-order image statistics to represent natural textures. We systematically explored neural selectivity in a high-dimensional texture space by combining texture synthesis and efficient-sampling techniques. This yielded parameterized models for individual texture-selective neurons. The models provided parsimonious but powerful predictors for each neuron’s preferred textures using a sparse combination of image statistics. As a whole population, the neuronal tuning was distributed in a way suitable for categorizing textures and quantitatively predicts human ability to discriminate textures. Together, we suggest that the collective representation of visual image statistics in V4 plays a key role in organizing the natural texture perception. PMID:25535362

In vitro selection of DNA elements highly responsive to the human T-cell lymphotropic virus type I transcriptional activator, Tax.

PubMed

Paca-Uccaralertkun, S; Zhao, L J; Adya, N; Cross, J V; Cullen, B R; Boros, I M; Giam, C Z

1994-01-01

The human T-cell lymphotropic virus type I (HTLV-I) transactivator, Tax, the ubiquitous transcriptional factor cyclic AMP (cAMP) response element-binding protein (CREB protein), and the 21-bp repeats in the HTLV-I transcriptional enhancer form a ternary nucleoprotein complex (L. J. Zhao and C. Z. Giam, Proc. Natl. Acad. Sci. USA 89:7070-7074, 1992). Using an antibody directed against the COOH-terminal region of Tax along with purified Tax and CREB proteins, we selected DNA elements bound specifically by the Tax-CREB complex in vitro. Two distinct but related groups of sequences containing the cAMP response element (CRE) flanked by long runs of G and C residues in the 5' and 3' regions, respectively, were preferentially recognized by Tax-CREB. In contrast, CREB alone binds only to CRE motifs (GNTGACG[T/C]) without neighboring G- or C-rich sequences. The Tax-CREB-selected sequences bear a striking resemblance to the 5' or 3' two-thirds of the HTLV-I 21-bp repeats and are highly inducible by Tax. Gel electrophoretic mobility shift assays, DNA transfection, and DNase I footprinting analyses indicated that the G- and C-rich sequences flanking the CRE motif are crucial for Tax-CREB-DNA ternary complex assembly and Tax transactivation but are not in direct contact with the Tax-CREB complex. These data show that Tax recruits CREB to form a multiprotein complex that specifically recognizes the viral 21-bp repeats. The expanded DNA binding specificity of Tax-CREB and the obligatory role the ternary Tax-CREB-DNA complex plays in transactivation reveal a novel mechanism for regulating the transcriptional activity of leucine zipper proteins like CREB.

Neural network system and methods for analysis of organic materials and structures using spectral data

DOEpatents

Meyer, B.J.; Sellers, J.P.; Thomsen, J.U.

1993-06-08

Apparatus and processes are described for recognizing and identifying materials. Characteristic spectra are obtained for the materials via spectroscopy techniques including nuclear magnetic resonance spectroscopy, infrared absorption analysis, x-ray analysis, mass spectroscopy and gas chromatography. Desired portions of the spectra may be selected and then placed in proper form and format for presentation to a number of input layer neurons in an offline neural network. The network is first trained according to a predetermined training process; it may then be employed to identify particular materials. Such apparatus and processes are particularly useful for recognizing and identifying organic compounds such as complex carbohydrates, whose spectra conventionally require a high level of training and many hours of hard work to identify, and are frequently indistinguishable from one another by human interpretation.

An evolutionary perspective on human physical activity: implications for health.

PubMed

Eaton, S Boyd; Eaton, Stanley B

2003-09-01

At present, human genes and human lives are incongruent, especially in affluent Western nations. When our current genome was originally selected, daily physical exertion was obligatory; our biochemistry and physiology are designed to function optimally in such circumstances. However, today's mechanized, technologically oriented conditions allow and even promote an unprecedentedly sedentary lifestyle. Many important health problems are affected by this imbalance, including atherosclerosis, obesity, age-related fractures and diabetes, among others. Most physicians recognize that regular exercise is a critical component of effective health promotion regimens, but there is substantial disagreement about details, most importantly volume: how much daily caloric expenditure, as physical activity, is desirable. Because epidemiology-based recommendations vary, often confusing and alienating the health-conscious public, an independent estimate, arising from a separate scientific discipline, is desirable, at least for purposes of triangulation. The retrojected level of ancestral physical activity might meet this need. The best available such reconstruction suggests that the World Health Organization's recommendation, a physical activity level of 1.75 ( approximately 2.1 MJ (490 kcal)/d), most closely approximates the Paleolithic standard, that for which our genetic makeup was originally selected.

Cross-continental differences in patterns of predation: will naive moose in Scandinavia ever learn?

PubMed Central

Sand, Håkan; Wikenros, Camilla; Wabakken, Petter; Liberg, Olof

2006-01-01

Predation has been recognized as a major selective force in the evolution of behavioural characteristics of mammals. As a consequence of local predator extinction, prey may lose knowledge about natural predators but usually express behavioural adjustments after return of predators. Human harvest may replace natural predation but prey selection may differ from that of natural predators leading to a change in the behavioural response of prey. We show that hunting success (HS) of re-colonizing wolves (Canis lupus) on moose (Alces alces) in Scandinavia was higher than reported in North America, where moose have been continuously exposed to wolves and grizzly bears. We found no evidence that moose expressed behavioural adjustments that lowered the HS of wolves in territories that had been occupied by wolves for up to 21 years. Moose behaviour towards wolves and humans typically differs in Scandinavia compared to North America. We explain the differences found to be caused by variation in predation pressure by large carnivores and the rate, and mode, of human harvest during the twentieth century. PMID:16777732

Structural basis for viral 5'-PPP-RNA recognition by human IFIT proteins.

PubMed

Abbas, Yazan M; Pichlmair, Andreas; Górna, Maria W; Superti-Furga, Giulio; Nagar, Bhushan

2013-02-07

Interferon-induced proteins with tetratricopeptide repeats (IFITs) are innate immune effector molecules that are thought to confer antiviral defence through disruption of protein-protein interactions in the host translation-initiation machinery. However, it was recently discovered that IFITs can directly recognize viral RNA bearing a 5'-triphosphate group (PPP-RNA), which is a molecular signature that distinguishes it from host RNA. Here we report crystal structures of human IFIT5, its complex with PPP-RNAs, and an amino-terminal fragment of IFIT1. The structures reveal a new helical domain that houses a positively charged cavity designed to specifically engage only single-stranded PPP-RNA, thus distinguishing it from the canonical cytosolic sensor of double-stranded viral PPP-RNA, retinoic acid-inducible gene I (RIG-I, also known as DDX58). Mutational analysis, proteolysis and gel-shift assays reveal that PPP-RNA is bound in a non-sequence-specific manner and requires a 5'-overhang of approximately three nucleotides. Abrogation of PPP-RNA binding in IFIT1 and IFIT5 was found to cause a defect in the antiviral response by human embryonic kidney cells. These results demonstrate the mechanism by which IFIT proteins selectively recognize viral RNA, and lend insight into their downstream effector function.

Are Africans, Europeans, and Asians Different "Races"? A Guided-Inquiry Lab for Introducing Undergraduate Students to Genetic Diversity and Preparing Them to Study Natural Selection

ERIC Educational Resources Information Center

Kalinowski, Steven T.; Andrews, Tessa M.; Leonard, Mary J.; Snodgrass, Meagan

2012-01-01

Many students do not recognize that individual organisms within populations vary, and this may make it difficult for them to recognize the essential role variation plays in natural selection. Also, many students have weak scientific reasoning skills, and this makes it difficult for them to recognize misconceptions they might have. This paper…

Characterization of 7A7, an anti-mouse EGFR monoclonal antibody proposed to be the mouse equivalent of cetuximab.

PubMed

He, Xuzhi; Cruz, Jazmina L; Joseph, Shannon; Pett, Nicola; Chew, Hui Yi; Tuong, Zewen K; Okano, Satomi; Kelly, Gabrielle; Veitch, Margaret; Simpson, Fiona; Wells, James W

2018-02-23

The Epidermal Growth Factor Receptor (EGFR) is selectively expressed on the surface of numerous tumours, such as non-small cell lung, ovarian, colorectal and head and neck carcinomas. EGFR has therefore become a target for cancer therapy. Cetuximab is a chimeric human/mouse monoclonal antibody (mAb) that binds to EGFR, where it both inhibits signaling and induces cell death by antibody-dependent cell mediated cytotoxicity (ADCC). Cetuximab has been approved for clinical use in patients with head and neck squamous cell carcinoma (HNSCC) and colorectal cancer. However, only 15-20% patients benefit from this drug, thus new strategies to improve cetuximab efficiency are required. We aimed to develop a reliable and easy preclinical mouse model to evaluate the efficacy of EGFR-targeted antibodies and examine the immune mechanisms involved in tumour regression. We selected an anti-mouse EGFR mAb, 7A7, which has been reported to be "mouse cetuximab" and to exhibit similar properties to its human counterpart. Unfortunately, we were unable to reproduce previous results obtained with the 7A7 mAb. In our hands, 7A7 failed to recognize mouse EGFR, both in native and reducing conditions. Moreover, in vivo administration of 7A7 in an EGFR-expressing HPV38 tumour model did not have any impact on tumour regression or animal survival. We conclude that 7A7 does not recognize mouse EGFR and therefore cannot be used as the mouse equivalent of cetuximab use in humans. As a number of groups have spent effort and resources with similar issues we feel that publication is a responsible approach.

Variable NK cell receptors and their MHC class I ligands in immunity, reproduction and human evolution.

PubMed

Parham, Peter; Moffett, Ashley

2013-02-01

Natural killer (NK) cells have roles in immunity and reproduction that are controlled by variable receptors that recognize MHC class I molecules. The variable NK cell receptors found in humans are specific to simian primates, in which they have progressively co-evolved with MHC class I molecules. The emergence of the MHC-C gene in hominids drove the evolution of a system of NK cell receptors for MHC-C molecules that is most elaborate in chimpanzees. By contrast, the human system of MHC-C receptors seems to have been subject to different selection pressures that have acted in competition on the immunological and reproductive functions of MHC class I molecules. We suggest that this compromise facilitated the development of the bigger brains that enabled archaic and modern humans to migrate out of Africa and populate other continents.

The yeast Holliday junction resolvase, CCE1, can restore wild-type mitochondrial DNA to human cells carrying rearranged mitochondrial DNA.

PubMed

Sembongi, Hiroshi; Di Re, Miriam; Bokori-Brown, Monika; Holt, Ian J

2007-10-01

Rearrangements of mitochondrial DNA (mtDNA) are a well-recognized cause of human disease; deletions are more frequent, but duplications are more readily transmitted to offspring. In theory, partial duplications of mtDNA can be resolved to partially deleted and wild-type (WT) molecules, via homologous recombination. Therefore, the yeast CCE1 gene, encoding a Holliday junction resolvase, was introduced into cells carrying partially duplicated or partially triplicated mtDNA. Some cell lines carrying the CCE1 gene had substantial amounts of WT mtDNA suggesting that the enzyme can mediate intramolecular recombination in human mitochondria. However, high levels of expression of CCE1 frequently led to mtDNA loss, and so it is necessary to strictly regulate the expression of CCE1 in human cells to ensure the selection and maintenance of WT mtDNA.

I-motif DNA structures are formed in the nuclei of human cells

NASA Astrophysics Data System (ADS)

Zeraati, Mahdi; Langley, David B.; Schofield, Peter; Moye, Aaron L.; Rouet, Romain; Hughes, William E.; Bryan, Tracy M.; Dinger, Marcel E.; Christ, Daniel

2018-06-01

Human genome function is underpinned by the primary storage of genetic information in canonical B-form DNA, with a second layer of DNA structure providing regulatory control. I-motif structures are thought to form in cytosine-rich regions of the genome and to have regulatory functions; however, in vivo evidence for the existence of such structures has so far remained elusive. Here we report the generation and characterization of an antibody fragment (iMab) that recognizes i-motif structures with high selectivity and affinity, enabling the detection of i-motifs in the nuclei of human cells. We demonstrate that the in vivo formation of such structures is cell-cycle and pH dependent. Furthermore, we provide evidence that i-motif structures are formed in regulatory regions of the human genome, including promoters and telomeric regions. Our results support the notion that i-motif structures provide key regulatory roles in the genome.

[Influenza virus receptors in the human airway].

PubMed

Shinya, Kyoko; Kawaoka, Yoshihiro

2006-06-01

Avian influenza A (H5N1) virus infections have resulted in more than 100 human deaths; yet, human-to-human transmission is rare. We demonstrated that the epithelial cells in the upper respiratory tract of humans mainly possess sialic acid linked to galactose by alpha 2,6 linkages (SA alpha 2,6Gal), a molecule preferentially recognized by human viruses. However, many cells in the respiratory bronchioles and alveoli possess SA alpha 2,3Gal, which is preferentially recognized by avian viruses. These facts are consistent with the observation that H5N1 viruses can be directly transmitted from birds to humans and cause serious lower respiratory tract damage in humans. Furthermore, this anatomical difference in receptor prevalence may explain why the spread of H5N1 viruses among humans is limited. However, since some H5N1 viruses isolated from humans recognize human virus receptors, additional changes must be required for these viruses to acquire the ability for efficient human-to-human transmission.

Designed Ankyrin Repeat Proteins: A New Approach to Mimic Complex Antigens for Diagnostic Purposes?

PubMed Central

Hausammann, Stefanie; Vogel, Monique; Kremer Hovinga, Johanna A.; Lacroix-Desmazes, Sebastien; Stadler, Beda M.; Horn, Michael P.

2013-01-01

Inhibitory antibodies directed against coagulation factor VIII (FVIII) can be found in patients with acquired and congenital hemophilia A. Such FVIII-inhibiting antibodies are routinely detected by the functional Bethesda Assay. However, this assay has a low sensitivity and shows a high inter-laboratory variability. Another method to detect antibodies recognizing FVIII is ELISA, but this test does not allow the distinction between inhibitory and non-inhibitory antibodies. Therefore, we aimed at replacing the intricate antigen FVIII by Designed Ankyrin Repeat Proteins (DARPins) mimicking the epitopes of FVIII inhibitors. As a model we used the well-described inhibitory human monoclonal anti-FVIII antibody, Bo2C11, for the selection on DARPin libraries. Two DARPins were selected binding to the antigen-binding site of Bo2C11, which mimic thus a functional epitope on FVIII. These DARPins inhibited the binding of the antibody to its antigen and restored FVIII activity as determined in the Bethesda assay. Furthermore, the specific DARPins were able to recognize the target antibody in human plasma and could therefore be used to test for the presence of Bo2C11-like antibodies in a large set of hemophilia A patients. These data suggest, that our approach might be used to isolate epitopes from different sets of anti-FVIII antibodies in order to develop an ELISA-based screening assay allowing the distinction of inhibitory and non-inhibitory anti-FVIII antibodies according to their antibody signatures. PMID:23626669

Bioelectronic tongue using heterodimeric human taste receptor for the discrimination of sweeteners with human-like performance.

PubMed

Song, Hyun Seok; Jin, Hye Jun; Ahn, Sae Ryun; Kim, Daesan; Lee, Sang Hun; Kim, Un-Kyung; Simons, Christopher T; Hong, Seunghun; Park, Tai Hyun

2014-10-28

The sense of taste helps humans to obtain information and form a picture of the world by recognizing chemicals in their environments. Over the past decade, large advances have been made in understanding the mechanisms of taste detection and mimicking its capability using artificial sensor devices. However, the detection capability of previous artificial taste sensors has been far inferior to that of animal tongues, in terms of its sensitivity and selectivity. Herein, we developed a bioelectronic tongue using heterodimeric human sweet taste receptors for the detection and discrimination of sweeteners with human-like performance, where single-walled carbon nanotube field-effect transistors were functionalized with nanovesicles containing human sweet taste receptors and used to detect the binding of sweeteners to the taste receptors. The receptors are heterodimeric G-protein-coupled receptors (GPCRs) composed of human taste receptor type 1 member 2 (hTAS1R2) and human taste receptor type 1 member 3 (hTAS1R3), which have multiple binding sites and allow a human tongue-like broad selectivity for the detection of sweeteners. This nanovesicle-based bioelectronic tongue can be a powerful tool for the detection of sweeteners as an alternative to labor-intensive and time-consuming cell-based assays and the sensory evaluation panels used in the food and beverage industry. Furthermore, this study also allows the artificial sensor to exam the functional activity of dimeric GPCRs.

Individual differences in cortical face selectivity predict behavioral performance in face recognition

PubMed Central

Huang, Lijie; Song, Yiying; Li, Jingguang; Zhen, Zonglei; Yang, Zetian; Liu, Jia

2014-01-01

In functional magnetic resonance imaging studies, object selectivity is defined as a higher neural response to an object category than other object categories. Importantly, object selectivity is widely considered as a neural signature of a functionally-specialized area in processing its preferred object category in the human brain. However, the behavioral significance of the object selectivity remains unclear. In the present study, we used the individual differences approach to correlate participants' face selectivity in the face-selective regions with their behavioral performance in face recognition measured outside the scanner in a large sample of healthy adults. Face selectivity was defined as the z score of activation with the contrast of faces vs. non-face objects, and the face recognition ability was indexed as the normalized residual of the accuracy in recognizing previously-learned faces after regressing out that for non-face objects in an old/new memory task. We found that the participants with higher face selectivity in the fusiform face area (FFA) and the occipital face area (OFA), but not in the posterior part of the superior temporal sulcus (pSTS), possessed higher face recognition ability. Importantly, the association of face selectivity in the FFA and face recognition ability cannot be accounted for by FFA response to objects or behavioral performance in object recognition, suggesting that the association is domain-specific. Finally, the association is reliable, confirmed by the replication from another independent participant group. In sum, our finding provides empirical evidence on the validity of using object selectivity as a neural signature in defining object-selective regions in the human brain. PMID:25071513

Amino acid signature enables proteins to recognize modified tRNA.

PubMed

Spears, Jessica L; Xiao, Xingqing; Hall, Carol K; Agris, Paul F

2014-02-25

Human tRNA(Lys3)UUU is the primer for HIV replication. The HIV-1 nucleocapsid protein, NCp7, facilitates htRNA(Lys3)UUU recruitment from the host cell by binding to and remodeling the tRNA structure. Human tRNA(Lys3)UUU is post-transcriptionally modified, but until recently, the importance of those modifications in tRNA recognition by NCp7 was unknown. Modifications such as the 5-methoxycarbonylmethyl-2-thiouridine at anticodon wobble position-34 and 2-methylthio-N(6)-threonylcarbamoyladenosine, adjacent to the anticodon at position-37, are important to the recognition of htRNA(Lys3)UUU by NCp7. Several short peptides selected from phage display libraries were found to also preferentially recognize these modifications. Evolutionary algorithms (Monte Carlo and self-consistent mean field) and assisted model building with energy refinement were used to optimize the peptide sequence in silico, while fluorescence assays were developed and conducted to verify the in silico results and elucidate a 15-amino acid signature sequence (R-W-Q/N-H-X2-F-Pho-X-G/A-W-R-X2-G, where X can be most amino acids, and Pho is hydrophobic) that recognized the tRNA's fully modified anticodon stem and loop domain, hASL(Lys3)UUU. Peptides of this sequence specifically recognized and bound modified htRNA(Lys3)UUU with an affinity 10-fold higher than that of the starting sequence. Thus, this approach provides an effective means of predicting sequences of RNA binding peptides that have better binding properties. Such peptides can be used in cell and molecular biology as well as biochemistry to explore RNA binding proteins and to inhibit those protein functions.

Affinity selection of Nipah and Hendra virus-related vaccine candidates from a complex random peptide library displayed on bacteriophage virus-like particles

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

Peabody, David S.; Chackerian, Bryce; Ashley, Carlee

The invention relates to virus-like particles of bacteriophage MS2 (MS2 VLPs) displaying peptide epitopes or peptide mimics of epitopes of Nipah Virus envelope glycoprotein that elicit an immune response against Nipah Virus upon vaccination of humans or animals. Affinity selection on Nipah Virus-neutralizing monoclonal antibodies using random sequence peptide libraries on MS2 VLPs selected peptides with sequence similarity to peptide sequences found within the envelope glycoprotein of Nipah itself, thus identifying the epitopes the antibodies recognize. The selected peptide sequences themselves are not necessarily identical in all respects to a sequence within Nipah Virus glycoprotein, and therefore may be referredmore » to as epitope mimics VLPs displaying these epitope mimics can serve as vaccine. On the other hand, display of the corresponding wild-type sequence derived from Nipah Virus and corresponding to the epitope mapped by affinity selection, may also be used as a vaccine.« less

Intercultural crew issues in long-duration spaceflight

NASA Technical Reports Server (NTRS)

Kraft, Norbert O.; Lyons, Terence J.; Binder, Heidi

2003-01-01

Before long-duration flights with international crews can be safely undertaken, potential interpersonal difficulties will need to be addressed. Crew performance breakdown has been recognized by the American Institute of Medicine, in scientific literature, and in popular culture. However, few studies of human interaction and performance in confined, isolated environments exist, and the data pertaining to those studies are mostly anecdotal. Many incidents involving crew interpersonal dynamics, those among flight crews, as well as between flight crews and ground controllers, are reported only in non-peer reviewed books and newspapers. Consequently, due to this lack of concrete knowledge, the selection of astronauts and cosmonauts has focused on individual rather than group selection. Additional selection criteria such as interpersonal and communication competence, along with intercultural training, will have a decisive impact on future mission success. Furthermore, industrial psychological research has demonstrated the ability to select a group based on compatibility. With all this in mind, it is essential to conduct further research on heterogeneous, multi-national crews including selection and training for long-duration space missions.

Antisense oligonucleotide inhibition of apolipoprotein C-III reduces plasma triglycerides in rodents, nonhuman primates, and humans.

PubMed

Graham, Mark J; Lee, Richard G; Bell, Thomas A; Fu, Wuxia; Mullick, Adam E; Alexander, Veronica J; Singleton, Walter; Viney, Nick; Geary, Richard; Su, John; Baker, Brenda F; Burkey, Jennifer; Crooke, Stanley T; Crooke, Rosanne M

2013-05-24

Elevated plasma triglyceride levels have been recognized as a risk factor for the development of coronary heart disease. Apolipoprotein C-III (apoC-III) represents both an independent risk factor and a key regulatory factor of plasma triglyceride concentrations. Furthermore, elevated apoC-III levels have been associated with metabolic syndrome and type 2 diabetes mellitus. To date, no selective apoC-III therapeutic agent has been evaluated in the clinic. To test the hypothesis that selective inhibition of apoC-III with antisense drugs in preclinical models and in healthy volunteers would reduce plasma apoC-III and triglyceride levels. Rodent- and human-specific second-generation antisense oligonucleotides were identified and evaluated in preclinical models, including rats, mice, human apoC-III transgenic mice, and nonhuman primates. We demonstrated the selective reduction of both apoC-III and triglyceride in all preclinical pharmacological evaluations. We also showed that inhibition of apoC-III was well tolerated and not associated with increased liver triglyceride deposition or hepatotoxicity. A double-blind, placebo-controlled, phase I clinical study was performed in healthy subjects. Administration of the human apoC-III antisense drug resulted in dose-dependent reductions in plasma apoC-III, concomitant lowering of triglyceride levels, and produced no clinically meaningful signals in the safety evaluations. Antisense inhibition of apoC-III in preclinical models and in a phase I clinical trial with healthy subjects produced potent, selective reductions in plasma apoC-III and triglyceride, 2 known risk factors for cardiovascular disease. This compelling pharmacological profile supports further clinical investigations in hypertriglyceridemic subjects.

Assortative mating and fragmentation within dog breeds.

PubMed

Björnerfeldt, Susanne; Hailer, Frank; Nord, Maria; Vilà, Carles

2008-01-28

There are around 400 internationally recognized dog breeds in the world today, with a remarkable diversity in size, shape, color and behavior. Breeds are considered to be uniform groups with similar physical characteristics, shaped by selection rooted in human preferences. This has led to a large genetic difference between breeds and a large extent of linkage disequilibrium within breeds. These characteristics are important for association mapping of candidate genes for diseases and therefore make dogs ideal models for gene mapping of human disorders. However, genetic uniformity within breeds may not always be the case. We studied patterns of genetic diversity within 164 poodles and compared it to 133 dogs from eight other breeds. Our analyses revealed strong population structure within poodles, with differences among some poodle groups as pronounced as those among other well-recognized breeds. Pedigree analysis going three generations back in time confirmed that subgroups within poodles result from assortative mating imposed by breed standards as well as breeder preferences. Matings have not taken place at random or within traditionally identified size classes in poodles. Instead, a novel set of five poodle groups was identified, defined by combinations of size and color, which is not officially recognized by the kennel clubs. Patterns of genetic diversity in other breeds suggest that assortative mating leading to fragmentation may be a common feature within many dog breeds. The genetic structure observed in poodles is the result of local mating patterns, implying that breed fragmentation may be different in different countries. Such pronounced structuring within dog breeds can increase the power of association mapping studies, but also represents a serious problem if ignored. In dog breeding, individuals are selected on the basis of morphology, behaviour, working or show purposes, as well as geographic population structure. The same processes which have historically created dog breeds are still ongoing, and create further subdivision within current dog breeds.

Assortative mating and fragmentation within dog breeds

PubMed Central

2008-01-01

Background There are around 400 internationally recognized dog breeds in the world today, with a remarkable diversity in size, shape, color and behavior. Breeds are considered to be uniform groups with similar physical characteristics, shaped by selection rooted in human preferences. This has led to a large genetic difference between breeds and a large extent of linkage disequilibrium within breeds. These characteristics are important for association mapping of candidate genes for diseases and therefore make dogs ideal models for gene mapping of human disorders. However, genetic uniformity within breeds may not always be the case. We studied patterns of genetic diversity within 164 poodles and compared it to 133 dogs from eight other breeds. Results Our analyses revealed strong population structure within poodles, with differences among some poodle groups as pronounced as those among other well-recognized breeds. Pedigree analysis going three generations back in time confirmed that subgroups within poodles result from assortative mating imposed by breed standards as well as breeder preferences. Matings have not taken place at random or within traditionally identified size classes in poodles. Instead, a novel set of five poodle groups was identified, defined by combinations of size and color, which is not officially recognized by the kennel clubs. Patterns of genetic diversity in other breeds suggest that assortative mating leading to fragmentation may be a common feature within many dog breeds. Conclusion The genetic structure observed in poodles is the result of local mating patterns, implying that breed fragmentation may be different in different countries. Such pronounced structuring within dog breeds can increase the power of association mapping studies, but also represents a serious problem if ignored. In dog breeding, individuals are selected on the basis of morphology, behaviour, working or show purposes, as well as geographic population structure. The same processes which have historically created dog breeds are still ongoing, and create further subdivision within current dog breeds. PMID:18226210

Lifespan development of attentiveness in domestic dogs: drawing parallels with humans

PubMed Central

Wallis, Lisa J.; Range, Friederike; Müller, Corsin A.; Serisier, Samuel; Huber, Ludwig; Zsó, Virányi

2014-01-01

Attention is pivotal to consciousness, perception, cognition, and working memory in all mammals, and therefore changes in attention over the lifespan are likely to influence development and aging of all of these functions. Due to their evolutionary and developmental history, the dog is being recognized as an important species for modeling human healthspan, aging and associated diseases. In this study, we investigated the normal lifespan development of attentiveness of pet dogs in naturalistic situations, and compared the resulting cross-sectional developmental trajectories with data from previous studies in humans. We tested a sample of 145 Border collies (6 months to 14 years) with humans and objects or food as attention attractors, in order to assess their attentional capture, sustained and selective attention, and sensorimotor abilities. Our results reveal differences in task relevance in sustained attentional performance when watching a human or a moving object, which may be explained by life-long learning processes involving such stimuli. During task switching we found that dogs’ selective attention and sensorimotor abilities showed differences between age groups, with performance peaking at middle age. Dogs’ sensorimotor abilities showed a quadratic distribution with age and were correlated with selective attention performance. Our results support the hypothesis that the development and senescence of sensorimotor and attentional control may be fundamentally interrelated. Additionally, attentional capture, sustained attention, and sensorimotor control developmental trajectories paralleled those found in humans. Given that the development of attention is similar across humans and dogs, we propose that the same regulatory mechanisms are likely to be present in both species. Finally, this cross-sectional study provides the first description of age group changes in attention over the lifespan of pet dogs. PMID:24570668

Body movement selectively shapes the neural representation of musical rhythms.

PubMed

Chemin, Baptiste; Mouraux, André; Nozaradan, Sylvie

2014-12-01

It is increasingly recognized that motor routines dynamically shape the processing of sensory inflow (e.g., when hand movements are used to feel a texture or identify an object). In the present research, we captured the shaping of auditory perception by movement in humans by taking advantage of a specific context: music. Participants listened to a repeated rhythmical sequence before and after moving their bodies to this rhythm in a specific meter. We found that the brain responses to the rhythm (as recorded with electroencephalography) after body movement were significantly enhanced at frequencies related to the meter to which the participants had moved. These results provide evidence that body movement can selectively shape the subsequent internal representation of auditory rhythms. © The Author(s) 2014.

Development of Amidine-Based Sphingosine Kinase 1 Nanomolar Inhibitors and Reduction of Sphingosine 1-Phosphate in Human Leukemia Cells

PubMed Central

Kennedy, Andrew J.; Mathews, Thomas P.; Kharel, Yugesh; Field, Saundra D.; Moyer, Morgan L.; East, James E.; Houck, Joseph D.; Lynch, Kevin R.; Macdonald, Timothy L.

2011-01-01

Sphingosine 1-phosphate (S1P) is a bioactive lipid that has been identified as an accelerant of cancer progression. The sphingosine kinases (SphKs) are the sole producers of S1P and thus SphK inhibitors may prove effective in cancer mitigation and chemosensitization. Of the two SphKs, SphK1 overexpression has been observed in a myriad of cancer cell lines and tissues, and has been recognized as the presumptive target over that of the poorly characterized SphK2. Herein, we present the design and synthesis of amidine-based nanomolar SphK1 subtype-selective inhibitors. A homology model of SphK1, trained with this library of amidine inhibitors, was then used to predict the activity of additional, more potent, inhibitors. Lastly, select amidine inhibitors were validated in human leukemia U937 cells, where they significantly reduced endogenous S1P levels at nanomolar concentrations. PMID:21495716

Concepts, requirements, and design approaches for building successful planning and scheduling systems

NASA Technical Reports Server (NTRS)

Hornstein, Rhoda Shaller; Willoughby, John K.

1991-01-01

Traditional practice of systems engineering management assumes requirements can be precisely determined and unambiguously defined prior to system design and implementation; practice further assumes requirements are held static during implementation. Human-computer decision support systems for service planning and scheduling applications do not conform well to these assumptions. Adaptation to the traditional practice of systems engineering management are required. Basic technology exists to support these adaptations. Additional innovations must be encouraged and nutured. Continued partnership between the programmatic and technical perspective assures proper balance of the impossible with the possible. Past problems have the following origins: not recognizing the unusual and perverse nature of the requirements for planning and scheduling; not recognizing the best starting point assumptions for the design; not understanding the type of system that being built; and not understanding the design consequences of the operations concept selected.

Selective cytotoxicity of an oxygen-radical-generating enzyme conjugated to a monoclonal antibody.

PubMed

Battelli, M G; Abbondanza, A; Tazzari, P L; Dinota, A; Rizzi, S; Grassi, G; Gobbi, M; Stirpe, F

1988-07-01

The monoclonal antibody 8A, which recognizes a human plasma cell-associated antigen, was covalently linked to xanthine oxidase in a conjugate maintaining both immunological and enzymatic properties. A significant degree of target cell lysis was obtained at an enzyme concentration that was ineffective on non-target cells and on myeloid staminal cells (CFU-GM). The cytotoxic activity was abolished by an excess of antibody, by allopurinol and by superoxide dismutase and catalase. A possible use of the conjugate for bone marrow purging in multiple myeloma patients is suggested.

Noise-robust speech recognition through auditory feature detection and spike sequence decoding.

PubMed

Schafer, Phillip B; Jin, Dezhe Z

2014-03-01

Speech recognition in noisy conditions is a major challenge for computer systems, but the human brain performs it routinely and accurately. Automatic speech recognition (ASR) systems that are inspired by neuroscience can potentially bridge the performance gap between humans and machines. We present a system for noise-robust isolated word recognition that works by decoding sequences of spikes from a population of simulated auditory feature-detecting neurons. Each neuron is trained to respond selectively to a brief spectrotemporal pattern, or feature, drawn from the simulated auditory nerve response to speech. The neural population conveys the time-dependent structure of a sound by its sequence of spikes. We compare two methods for decoding the spike sequences--one using a hidden Markov model-based recognizer, the other using a novel template-based recognition scheme. In the latter case, words are recognized by comparing their spike sequences to template sequences obtained from clean training data, using a similarity measure based on the length of the longest common sub-sequence. Using isolated spoken digits from the AURORA-2 database, we show that our combined system outperforms a state-of-the-art robust speech recognizer at low signal-to-noise ratios. Both the spike-based encoding scheme and the template-based decoding offer gains in noise robustness over traditional speech recognition methods. Our system highlights potential advantages of spike-based acoustic coding and provides a biologically motivated framework for robust ASR development.

Potent neutralization of botulinum neurotoxin/B by synergistic action of antibodies recognizing protein and ganglioside receptor binding domain.

PubMed

Chen, Changchun; Wang, Shuhui; Wang, Huajing; Mao, Xiaoyan; Zhang, Tiancheng; Ji, Guanghui; Shi, Xin; Xia, Tian; Lu, Weijia; Zhang, Dapeng; Dai, Jianxin; Guo, Yajun

2012-01-01

Botulinum neurotoxins (BoNTs), the causative agents for life-threatening human disease botulism, have been recognized as biological warfare agents. Monoclonal antibody (mAb) therapeutics hold considerable promise as BoNT therapeutics, but the potencies of mAbs against BoNTs are usually less than that of polyclonal antibodies (or oligoclonal antibodies). The confirmation of key epitopes with development of effective mAb is urgently needed. We selected 3 neutralizing mAbs which recognize different non-overlapping epitopes of BoNT/B from a panel of neutralizing antibodies against BoNT/B. By comparing the neutralizing effects among different combination groups, we found that 8E10, response to ganglioside receptor binding site, could synergy with 5G10 and 2F4, recognizing non-overlapping epitopes within Syt II binding sites. However, the combination of 5G10 with 2F4 blocking protein receptor binding sites did not achieve synergistical effects. Moreover, we found that the binding epitope of 8E10 was conserved among BoNT A, B, E, and F, which might cross-protect the challenge of different serotypes of BoNTs in vivo. The combination of two mAbs recognizing different receptors' binding domain in BoNTs has a synergistic effect. 8E10 is a potential universal partner for the synergistical combination with other mAb against protein receptor binding domain in BoNTs of other serotypes.

Executive summary and conclusions from the European Hydration Institute Expert Conference on human hydration, health, and performance.

PubMed

Benton, D; Braun, H; Cobo, J C; Edmonds, C; Elmadfa, I; El-Sharkawy, A; Feehally, J; Gellert, R; Holdsworth, J; Kapsokefalou, M; Kenney, W L; Leiper, J B; Macdonald, I A; Maffeis, C; Maughan, R J; Shirreffs, S M; Toth-Heyn, P; Watson, P

2015-09-01

On April 7-8, 2014, the European Hydration Institute hosted a small group of experts at Castle Combe Manor House, United Kingdom, to discuss a range of issues related to human hydration, health, and performance. The meeting included 18 recognized experts who brought a wealth of experience and knowledge to the topics under review. Eight selected topics were addressed, with the key issues being briefly presented before an in-depth discussion. Presented here is the executive summary and conclusions from this meeting. © The Author(s) 2015. Published by Oxford University Press on behalf of the International Life Sciences Institute. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Recognition of voice commands using adaptation of foreign language speech recognizer via selection of phonetic transcriptions

NASA Astrophysics Data System (ADS)

Maskeliunas, Rytis; Rudzionis, Vytautas

2011-06-01

In recent years various commercial speech recognizers have become available. These recognizers provide the possibility to develop applications incorporating various speech recognition techniques easily and quickly. All of these commercial recognizers are typically targeted to widely spoken languages having large market potential; however, it may be possible to adapt available commercial recognizers for use in environments where less widely spoken languages are used. Since most commercial recognition engines are closed systems the single avenue for the adaptation is to try set ways for the selection of proper phonetic transcription methods between the two languages. This paper deals with the methods to find the phonetic transcriptions for Lithuanian voice commands to be recognized using English speech engines. The experimental evaluation showed that it is possible to find phonetic transcriptions that will enable the recognition of Lithuanian voice commands with recognition accuracy of over 90%.

Understanding the abstract role of speech in communication at 12 months.

PubMed

Martin, Alia; Onishi, Kristine H; Vouloumanos, Athena

2012-04-01

Adult humans recognize that even unfamiliar speech can communicate information between third parties, demonstrating an ability to separate communicative function from linguistic content. We examined whether 12-month-old infants understand that speech can communicate before they understand the meanings of specific words. Specifically, we test the understanding that speech permits the transfer of information about a Communicator's target object to a Recipient. Initially, the Communicator selectively grasped one of two objects. In test, the Communicator could no longer reach the objects. She then turned to the Recipient and produced speech (a nonsense word) or non-speech (coughing). Infants looked longer when the Recipient selected the non-target than the target object when the Communicator had produced speech but not coughing (Experiment 1). Looking time patterns differed from the speech condition when the Recipient rather than the Communicator produced the speech (Experiment 2), and when the Communicator produced a positive emotional vocalization (Experiment 3), but did not differ when the Recipient had previously received information about the target by watching the Communicator's selective grasping (Experiment 4). Thus infants understand the information-transferring properties of speech and recognize some of the conditions under which others' information states can be updated. These results suggest that infants possess an abstract understanding of the communicative function of speech, providing an important potential mechanism for language and knowledge acquisition. Copyright © 2011 Elsevier B.V. All rights reserved.

Structural basis for viral 5′-PPP-RNA recognition by human IFIT proteins

PubMed Central

Abbas, Yazan M.; Pichlmair, Andreas; Górna, Maria W.; Superti-Furga, Giulio; Nagar, Bhushan

2016-01-01

IFIT proteins are interferon-inducible, innate immune effector molecules that are thought to confer antiviral defence through disruption of protein-protein interactions in the host translation initiation machinery. However, recently it was discovered that IFITs could directly recognize viral RNA bearing a 5′-triphosphate group (PPP-RNA), which is a molecular signature that distinguishes it from host RNA. Here, we report crystal structures of human IFIT5, its complex with PPP-RNAs, and an N-terminal fragment of IFIT1. The structures reveal a new helical domain that houses a positively charged cavity designed to specifically engage only single stranded PPP-RNA, thus distinguishing it from the canonical cytosolic sensor of double stranded viral PPP-RNA, RIG-I. Mutational analysis, proteolysis and gel-shift assays reveal that PPP-RNA is bound in a non-sequence specific manner and requires approximately a 3-nucleotide 5′-overhang. Abrogation of PPP-RNA binding in IFIT1 and IFIT5 were found to cause a defect in the anti-viral response by HEK cells. These results demonstrate the mechanism by which IFIT proteins selectively recognize viral RNA and lend insight into their downstream effector function. PMID:23334420

The neural code for face orientation in the human fusiform face area.

PubMed

Ramírez, Fernando M; Cichy, Radoslaw M; Allefeld, Carsten; Haynes, John-Dylan

2014-09-03

Humans recognize faces and objects with high speed and accuracy regardless of their orientation. Recent studies have proposed that orientation invariance in face recognition involves an intermediate representation where neural responses are similar for mirror-symmetric views. Here, we used fMRI, multivariate pattern analysis, and computational modeling to investigate the neural encoding of faces and vehicles at different rotational angles. Corroborating previous studies, we demonstrate a representation of face orientation in the fusiform face-selective area (FFA). We go beyond these studies by showing that this representation is category-selective and tolerant to retinal translation. Critically, by controlling for low-level confounds, we found the representation of orientation in FFA to be compatible with a linear angle code. Aspects of mirror-symmetric coding cannot be ruled out when FFA mean activity levels are considered as a dimension of coding. Finally, we used a parametric family of computational models, involving a biased sampling of view-tuned neuronal clusters, to compare different face angle encoding models. The best fitting model exhibited a predominance of neuronal clusters tuned to frontal views of faces. In sum, our findings suggest a category-selective and monotonic code of face orientation in the human FFA, in line with primate electrophysiology studies that observed mirror-symmetric tuning of neural responses at higher stages of the visual system, beyond the putative homolog of human FFA. Copyright © 2014 the authors 0270-6474/14/3412155-13$15.00/0.

Targeting endogenous proteins for degradation through the affinity-directed protein missile system.

PubMed

Fulcher, Luke J; Hutchinson, Luke D; Macartney, Thomas J; Turnbull, Craig; Sapkota, Gopal P

2017-05-01

Targeted proteolysis of endogenous proteins is desirable as a research toolkit and in therapeutics. CRISPR/Cas9-mediated gene knockouts are irreversible and often not feasible for many genes. Similarly, RNA interference approaches necessitate prolonged treatments, can lead to incomplete knockdowns and are often associated with off-target effects. Targeted proteolysis can overcome these limitations. In this report, we describe an affinity-directed protein missile (AdPROM) system that harbours the von Hippel-Lindau (VHL) protein, the substrate receptor of the Cullin2 (CUL2) E3 ligase complex, tethered to polypeptide binders that selectively bind and recruit endogenous target proteins to the CUL2-E3 ligase complex for ubiquitination and proteasomal degradation. By using synthetic monobodies that selectively bind the protein tyrosine phosphatase SHP2 and a camelid-derived VHH nanobody that selectively binds the human ASC protein, we demonstrate highly efficient AdPROM-mediated degradation of endogenous SHP2 and ASC in human cell lines. We show that AdPROM-mediated loss of SHP2 in cells impacts SHP2 biology. This study demonstrates for the first time that small polypeptide binders that selectively recognize endogenous target proteins can be exploited for AdPROM-mediated destruction of the target proteins. © 2017 The Authors.

Targeting endogenous proteins for degradation through the affinity-directed protein missile system

PubMed Central

Fulcher, Luke J.; Hutchinson, Luke D.; Macartney, Thomas J.; Turnbull, Craig

2017-01-01

Targeted proteolysis of endogenous proteins is desirable as a research toolkit and in therapeutics. CRISPR/Cas9-mediated gene knockouts are irreversible and often not feasible for many genes. Similarly, RNA interference approaches necessitate prolonged treatments, can lead to incomplete knockdowns and are often associated with off-target effects. Targeted proteolysis can overcome these limitations. In this report, we describe an affinity-directed protein missile (AdPROM) system that harbours the von Hippel–Lindau (VHL) protein, the substrate receptor of the Cullin2 (CUL2) E3 ligase complex, tethered to polypeptide binders that selectively bind and recruit endogenous target proteins to the CUL2-E3 ligase complex for ubiquitination and proteasomal degradation. By using synthetic monobodies that selectively bind the protein tyrosine phosphatase SHP2 and a camelid-derived VHH nanobody that selectively binds the human ASC protein, we demonstrate highly efficient AdPROM-mediated degradation of endogenous SHP2 and ASC in human cell lines. We show that AdPROM-mediated loss of SHP2 in cells impacts SHP2 biology. This study demonstrates for the first time that small polypeptide binders that selectively recognize endogenous target proteins can be exploited for AdPROM-mediated destruction of the target proteins. PMID:28490657

5 CFR 5501.103 - Gifts from federally recognized Indian tribes or Alaska Native villages or regional or village...

Code of Federal Regulations, 2010 CFR

2010-01-01

... Administrative Personnel DEPARTMENT OF HEALTH AND HUMAN SERVICES SUPPLEMENTAL STANDARDS OF ETHICAL CONDUCT FOR EMPLOYEES OF THE DEPARTMENT OF HEALTH AND HUMAN SERVICES § 5501.103 Gifts from federally recognized Indian...

5 CFR 5501.103 - Gifts from federally recognized Indian tribes or Alaska Native villages or regional or village...

Code of Federal Regulations, 2011 CFR

2011-01-01

... Administrative Personnel DEPARTMENT OF HEALTH AND HUMAN SERVICES SUPPLEMENTAL STANDARDS OF ETHICAL CONDUCT FOR EMPLOYEES OF THE DEPARTMENT OF HEALTH AND HUMAN SERVICES § 5501.103 Gifts from federally recognized Indian...

5 CFR 5501.103 - Gifts from federally recognized Indian tribes or Alaska Native villages or regional or village...

Code of Federal Regulations, 2013 CFR

2013-01-01

... Administrative Personnel DEPARTMENT OF HEALTH AND HUMAN SERVICES SUPPLEMENTAL STANDARDS OF ETHICAL CONDUCT FOR EMPLOYEES OF THE DEPARTMENT OF HEALTH AND HUMAN SERVICES § 5501.103 Gifts from federally recognized Indian...

5 CFR 5501.103 - Gifts from federally recognized Indian tribes or Alaska Native villages or regional or village...

Code of Federal Regulations, 2012 CFR

2012-01-01

... Administrative Personnel DEPARTMENT OF HEALTH AND HUMAN SERVICES SUPPLEMENTAL STANDARDS OF ETHICAL CONDUCT FOR EMPLOYEES OF THE DEPARTMENT OF HEALTH AND HUMAN SERVICES § 5501.103 Gifts from federally recognized Indian...

5 CFR 5501.103 - Gifts from federally recognized Indian tribes or Alaska Native villages or regional or village...

Code of Federal Regulations, 2014 CFR

2014-01-01

... Administrative Personnel DEPARTMENT OF HEALTH AND HUMAN SERVICES SUPPLEMENTAL STANDARDS OF ETHICAL CONDUCT FOR EMPLOYEES OF THE DEPARTMENT OF HEALTH AND HUMAN SERVICES § 5501.103 Gifts from federally recognized Indian...

Adding words to the brain's visual dictionary: novel word learning selectively sharpens orthographic representations in the VWFA.

PubMed

Glezer, Laurie S; Kim, Judy; Rule, Josh; Jiang, Xiong; Riesenhuber, Maximilian

2015-03-25

The nature of orthographic representations in the human brain is still subject of much debate. Recent reports have claimed that the visual word form area (VWFA) in left occipitotemporal cortex contains an orthographic lexicon based on neuronal representations highly selective for individual written real words (RWs). This theory predicts that learning novel words should selectively increase neural specificity for these words in the VWFA. We trained subjects to recognize novel pseudowords (PWs) and used fMRI rapid adaptation to compare neural selectivity with RWs, untrained PWs (UTPWs), and trained PWs (TPWs). Before training, PWs elicited broadly tuned responses, whereas responses to RWs indicated tight tuning. After training, TPW responses resembled those of RWs, whereas UTPWs continued to show broad tuning. This change in selectivity was specific to the VWFA. Therefore, word learning appears to selectively increase neuronal specificity for the new words in the VWFA, thereby adding these words to the brain's visual dictionary. Copyright © 2015 the authors 0270-6474/15/354965-08$15.00/0.

Method development for comprehensive extraction and analysis of marine toxins: Liquid-liquid extraction and tandem liquid chromatography separations coupled to electrospray tandem mass spectrometry

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

Wunschel, David S.; Valenzuela, Blandina R.; Kaiser, Brooke L. Deatherage

Toxins from biological sources are recognized as potential chemical weapon threats, with saxitoxin and ricin listed by the chemical weapons convention (CWC) as schedule one agents (CWC reference). These two toxins represent a metabolite (saxitoxin) and protein (ricin) from algal and plant sources, respectively. An array of toxins have been listed as "select agents" by the Health and Human Services (HHS) select agent program, including ricin, abrin, saxitoxin, tetrodotoxin, specific paralytic alpha conotoxin peptides, T-2 toxin, diacetoxyscirpenols, botulinum toxins, and staphylococcal enterotoxins [1]. The quantities of these toxins dictate whether they are considered select agents with federal oversight of theirmore » storage and use. While this list captures some of the naturally occurring toxins that may pose a threat to the public, there are a number of other naturally occurring toxins that may also be a concern.« less

Selenium- and tellurium-containing multifunctional redox agents as biochemical redox modulators with selective cytotoxicity.

PubMed

Jamier, Vincent; Ba, Lalla A; Jacob, Claus

2010-09-24

Various human diseases, including different types of cancer, are associated with a disturbed intracellular redox balance and oxidative stress (OS). The past decade has witnessed the emergence of redox-modulating compounds able to utilize such pre-existing disturbances in the redox state of sick cells for therapeutic advantage. Selenium- and tellurium-based agents turn the oxidizing redox environment present in certain cancer cells into a lethal cocktail of reactive species that push these cells over a critical redox threshold and ultimately kill them through apoptosis. This kind of toxicity is highly selective: normal, healthy cells remain largely unaffected, since changes to their naturally low levels of oxidizing species produce little effect. To further improve selectivity, multifunctional sensor/effector agents are now required that recognize the biochemical signature of OS in target cells. The synthesis of such compounds provides interesting challenges for chemistry in the future.

Genomic Microbial Epidemiology Is Needed to Comprehend the Global Problem of Antibiotic Resistance and to Improve Pathogen Diagnosis.

PubMed

Wyrsch, Ethan R; Roy Chowdhury, Piklu; Chapman, Toni A; Charles, Ian G; Hammond, Jeffrey M; Djordjevic, Steven P

2016-01-01

Contamination of waste effluent from hospitals and intensive food animal production with antimicrobial residues is an immense global problem. Antimicrobial residues exert selection pressures that influence the acquisition of antimicrobial resistance and virulence genes in diverse microbial populations. Despite these concerns there is only a limited understanding of how antimicrobial residues contribute to the global problem of antimicrobial resistance. Furthermore, rapid detection of emerging bacterial pathogens and strains with resistance to more than one antibiotic class remains a challenge. A comprehensive, sequence-based genomic epidemiological surveillance model that captures essential microbial metadata is needed, both to improve surveillance for antimicrobial resistance and to monitor pathogen evolution. Escherichia coli is an important pathogen causing both intestinal [intestinal pathogenic E. coli (IPEC)] and extraintestinal [extraintestinal pathogenic E. coli (ExPEC)] disease in humans and food animals. ExPEC are the most frequently isolated Gram negative pathogen affecting human health, linked to food production practices and are often resistant to multiple antibiotics. Cattle are a known reservoir of IPEC but they are not recognized as a source of ExPEC that impact human or animal health. In contrast, poultry are a recognized source of multiple antibiotic resistant ExPEC, while swine have received comparatively less attention in this regard. Here, we review what is known about ExPEC in swine and how pig production contributes to the problem of antibiotic resistance.

Spatiotemporal dynamics underlying object completion in human ventral visual cortex.

PubMed

Tang, Hanlin; Buia, Calin; Madhavan, Radhika; Crone, Nathan E; Madsen, Joseph R; Anderson, William S; Kreiman, Gabriel

2014-08-06

Natural vision often involves recognizing objects from partial information. Recognition of objects from parts presents a significant challenge for theories of vision because it requires spatial integration and extrapolation from prior knowledge. Here we recorded intracranial field potentials of 113 visually selective electrodes from epilepsy patients in response to whole and partial objects. Responses along the ventral visual stream, particularly the inferior occipital and fusiform gyri, remained selective despite showing only 9%-25% of the object areas. However, these visually selective signals emerged ∼100 ms later for partial versus whole objects. These processing delays were particularly pronounced in higher visual areas within the ventral stream. This latency difference persisted when controlling for changes in contrast, signal amplitude, and the strength of selectivity. These results argue against a purely feedforward explanation of recognition from partial information, and provide spatiotemporal constraints on theories of object recognition that involve recurrent processing. Copyright © 2014 Elsevier Inc. All rights reserved.

Validation of a new classifier for the automated analysis of the human epidermal growth factor receptor 2 (HER2) gene amplification in breast cancer specimens

PubMed Central

2013-01-01

Amplification of the human epidermal growth factor receptor 2 (HER2) is a prognostic marker for poor clinical outcome and a predictive marker for therapeutic response to targeted therapies in breast cancer patients. With the introduction of anti-HER2 therapies, accurate assessment of HER2 status has become essential. Fluorescence in situ hybridization (FISH) is a widely used technique for the determination of HER2 status in breast cancer. However, the manual signal enumeration is time-consuming. Therefore, several companies like MetaSystem have developed automated image analysis software. Some of these signal enumeration software employ the so called “tile-sampling classifier”, a programming algorithm through which the software quantifies fluorescent signals in images on the basis of square tiles of fixed dimensions. Considering that the size of tile does not always correspond to the size of a single tumor cell nucleus, some users argue that this analysis method might not completely reflect the biology of cells. For that reason, MetaSystems has developed a new classifier which is able to recognize nuclei within tissue sections in order to determine the HER2 amplification status on nuclei basis. We call this new programming algorithm “nuclei-sampling classifier”. In this study, we evaluated the accuracy of the “nuclei-sampling classifier” in determining HER2 gene amplification by FISH in nuclei of breast cancer cells. To this aim, we randomly selected from our cohort 64 breast cancer specimens (32 nonamplified and 32 amplified) and we compared results obtained through manual scoring and through this new classifier. The new classifier automatically recognized individual nuclei. The automated analysis was followed by an optional human correction, during which the user interacted with the software in order to improve the selection of cell nuclei automatically selected. Overall concordance between manual scoring and automated nuclei-sampling analysis was 98.4% (100% for nonamplified cases and 96.9% for amplified cases). However, after human correction, concordance between the two methods was 100%. We conclude that the nuclei-based classifier is a new available tool for automated quantitative HER2 FISH signals analysis in nuclei in breast cancer specimen and it can be used for clinical purposes. PMID:23379971

A human cytochrome P-450 is recognized by anti-liver/kidney microsome antibodies in autoimmune chronic hepatitis.

PubMed

Kiffel, L; Loeper, J; Homberg, J C; Leroux, J P

1989-02-28

1- Anti-liver/kidney microsome autoantibodies type 1 (anti-LKM1), observed in some children with chronic active hepatitis, were used to isolate their antigen in human liver microsomes. A protein, called P-LKM1 was thus purified. This protein was recognized by a rabbit antiserum directed against the related human cytochromes P-450 bufI and P-450 bufII. 2- A human liver microsomal protein immunoprecipitated with anti-LKM1 sera was also recognized by anti cytochromes P-450 bufI/II antibodies. 3- Anti-LKM1 antibodies potently inhibited microsomal bufuralol 1'-hydroxylation. These results displayed the possible identity between cytochrome P-450 bufI/II and LKM1 antigen.

Repair of DNA-polypeptide crosslinks by human excision nuclease

NASA Astrophysics Data System (ADS)

Reardon, Joyce T.; Sancar, Aziz

2006-03-01

DNA-protein crosslinks are relatively common DNA lesions that form during the physiological processing of DNA by replication and recombination proteins, by side reactions of base excision repair enzymes, and by cellular exposure to bifunctional DNA-damaging agents such as platinum compounds. The mechanism by which pathological DNA-protein crosslinks are repaired in humans is not known. In this study, we investigated the mechanism of recognition and repair of protein-DNA and oligopeptide-DNA crosslinks by the human excision nuclease. Under our assay conditions, the human nucleotide excision repair system did not remove a 16-kDa protein crosslinked to DNA at a detectable level. However, 4- and 12-aa-long oligopeptides crosslinked to the DNA backbone were recognized by some of the damage recognition factors of the human excision nuclease with moderate selectivity and were excised from DNA at relatively efficient rates. Our data suggest that, if coupled with proteolytic degradation of the crosslinked protein, the human excision nuclease may be the major enzyme system for eliminating protein-DNA crosslinks from the genome. damage recognition | nucleotide excision repair

B-Lymphocytes Expressing an Ig Specificity Recognizing the Pancreatic β-Cell Autoantigen Peripherin Are Potent Contributors to Type 1 Diabetes Development in NOD Mice

PubMed Central

Leeth, Caroline M.; Racine, Jeremy; Chapman, Harold D.; Arpa, Berta; Carrillo, Jorge; Carrascal, Jorge; Wang, Qiming; Ratiu, Jeremy; Egia-Mendikute, Leire; Rosell-Mases, Estela; Stratmann, Thomas

2016-01-01

Although the autoimmune destruction of pancreatic β-cells underlying type 1 diabetes (T1D) development is ultimately mediated by T cells in NOD mice and also likely in humans, B cells play an additional key pathogenic role. It appears that the expression of plasma membrane–bound Ig molecules that efficiently capture β-cell antigens allows autoreactive B cells that bypass normal tolerance induction processes to be the subset of antigen-presenting cells most efficiently activating diabetogenic T cells. NOD mice transgenically expressing Ig molecules recognizing antigens that are (insulin) or are not (hen egg lysozyme [HEL]) expressed by β-cells have proven useful in dissecting the developmental basis of diabetogenic B cells. However, these transgenic Ig specificities were originally selected for their ability to recognize insulin or HEL as foreign, rather than autoantigens. Thus, we generated and characterized NOD mice transgenically expressing an Ig molecule representative of a large proportion of naturally occurring islet-infiltrating B cells in NOD mice recognizing the neuronal antigen peripherin. Transgenic peripherin-autoreactive B cells infiltrate NOD pancreatic islets, acquire an activated proliferative phenotype, and potently support accelerated T1D development. These results support the concept of neuronal autoimmunity as a pathogenic feature of T1D, and targeting such responses could ultimately provide an effective disease intervention approach. PMID:26961115

Speech Recognition Using Multiple Features and Multiple Recognizers

DTIC Science & Technology

1991-12-03

6 2.1 Introduction ............................................... 6 2.2 Human Speech Communication Process...119 How to Setup ASRT.......................................... 119 How to Use Interactive Menus .................................. 120...recognize a word from an acoustic signal. The human ear and brain perform this type of recognition with incredible speed and precision. Even though

Evidence that a synthetic amyloid-ß oligomer-binding peptide (ABP) targets amyloid-ß deposits in transgenic mouse brain and human Alzheimer's disease brain.

PubMed

Chakravarthy, Balu; Ito, Shingo; Atkinson, Trevor; Gaudet, Chantal; Ménard, Michel; Brown, Leslie; Whitfield, James

2014-03-14

The synthetic ~5 kDa ABP (amyloid-ß binding peptide) consists of a region of the 228 kDa human pericentrioloar material-1 (PCM-1) protein that selectively and avidly binds in vitro Aβ1-42 oligomers, believed to be key co-drivers of Alzheimer's disease (AD), but not monomers (Chakravarthy et al., (2013) [3]). ABP also prevents Aß1-42 from triggering the apoptotic death of cultured human SHSY5Y neuroblasts, likely by sequestering Aß oligomers, suggesting that it might be a potential AD therapeutic. Here we support this possibility by showing that ABP also recognizes and binds Aβ1-42 aggregates in sections of cortices and hippocampi from brains of AD transgenic mice and human AD patients. More importantly, ABP targets Aβ1-42 aggregates when microinjected into the hippocampi of the brains of live AD transgenic mice. Crown Copyright © 2014. Published by Elsevier Inc. All rights reserved.

Bioelectronic Device Mimicking Human Sensory System based on Nanovesicle-Carbon Nanotube Hybrid Structure

NASA Astrophysics Data System (ADS)

Kim, Daesan; Jin, Hye; Lee, San; Kim, Tae; Park, Juhun; Song, Hyun; Park, Tai; Hong, Seunghun

2013-03-01

We have developed a nanovesicle-based bioelectronic nose (NBN) that could mimic the receptor-mediated signal transmission of human olfactory systems and recognize a specific odorant. The NBN was comprised of a single-walled carbon nanotube (CNT)-based field effect transistor and cell-derived nanovesicles containing human olfactory receptors and calcium ion signal pathways. Importantly, the NBN took advantages of cell signal pathways for sensing signal amplification. It enabled ~100 times higher sensitivity than that of previous bioelectronic noses based on only olfactory receptor protein and CNT transistors. The NBN sensors exhibited a high sensitivity of 1 fM detection limit and a human-like selectivity with single-carbon-atomic resolution. Furthermore, these sensors could mimic a receptor-mediated cellular signal transmission in live cells. This versatile sensor platform should be useful for the study of molecular recognition and biological processes on cell membranes and also for various practical applications such as food conditioning and medical diagnostics.

Nanovesicle-based bioelectronic nose platform mimicking human olfactory signal transduction.

PubMed

Jin, Hye Jun; Lee, Sang Hun; Kim, Tae Hyun; Park, Juhun; Song, Hyun Seok; Park, Tai Hyun; Hong, Seunghun

2012-05-15

We developed a nanovesicle-based bioelectronic nose (NBN) that could recognize a specific odorant and mimic the receptor-mediated signal transmission of human olfactory systems. To build an NBN, we combined a single-walled carbon nanotube-based field effect transistor with cell-derived nanovesicles containing human olfactory receptors and calcium ion signal pathways. Importantly, the NBN took advantages of cell signal pathways for sensing signal amplification, enabling ≈ 100 times better sensitivity than that of previous bioelectronic noses based on only olfactory receptor protein and carbon nanotube transistors. The NBN sensors exhibited a human-like selectivity with single-carbon-atomic resolution and a high sensitivity of 1 fM detection limit. Moreover, this sensor platform could mimic a receptor-meditated cellular signal transmission in live cells. This sensor platform can be utilized for the study of molecular recognition and biological processes occurring at cell membranes and also for various practical applications such as food screening and medical diagnostics. Copyright © 2012 Elsevier B.V. All rights reserved.

Recognizing the Effects of Comprehension Language Barriers and Adaptability Cultural Barriers on Selected First-Generation Undergraduate Vietnamese Students

ERIC Educational Resources Information Center

Phan, Christian Phuoc-Lanh

2009-01-01

This investigation is about recognizing the effects of comprehension language barriers and adaptability cultural barriers on selected first-generation Vietnamese undergraduate students in the Puget Sound region of Washington State. Most Vietnamese students know little or no English before immigrating to the United States; as such, language and…

The human RNA-binding protein and E3 ligase MEX-3C binds the MEX-3-recognition element (MRE) motif with high affinity.

PubMed

Yang, Lingna; Wang, Chongyuan; Li, Fudong; Zhang, Jiahai; Nayab, Anam; Wu, Jihui; Shi, Yunyu; Gong, Qingguo

2017-09-29

MEX-3 is a K-homology (KH) domain-containing RNA-binding protein first identified as a translational repressor in Caenorhabditis elegans , and its four orthologs (MEX-3A-D) in human and mouse were subsequently found to have E3 ubiquitin ligase activity mediated by a RING domain and critical for RNA degradation. Current evidence implicates human MEX-3C in many essential biological processes and suggests a strong connection with immune diseases and carcinogenesis. The highly conserved dual KH domains in MEX-3 proteins enable RNA binding and are essential for the recognition of the 3'-UTR and post-transcriptional regulation of MEX-3 target transcripts. However, the molecular mechanisms of translational repression and the consensus RNA sequence recognized by the MEX-3C KH domain are unknown. Here, using X-ray crystallography and isothermal titration calorimetry, we investigated the RNA-binding activity and selectivity of human MEX-3C dual KH domains. Our high-resolution crystal structures of individual KH domains complexed with a noncanonical U-rich and a GA-rich RNA sequence revealed that the KH1/2 domains of human MEX-3C bound MRE10, a 10-mer RNA (5'-CAGAGUUUAG-3') consisting of an eight-nucleotide MEX-3-recognition element (MRE) motif, with high affinity. Of note, we also identified a consensus RNA motif recognized by human MEX-3C. The potential RNA-binding sites in the 3'-UTR of the human leukocyte antigen serotype ( HLA-A2 ) mRNA were mapped with this RNA-binding motif and further confirmed by fluorescence polarization. The binding motif identified here will provide valuable information for future investigations of the functional pathways controlled by human MEX-3C and for predicting potential mRNAs regulated by this enzyme. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Personal relevance and the human right hemisphere.

PubMed

Van Lancker, D

1991-09-01

Brain damage can selectively disrupt or distort information and ability across the range of human behaviors. One domain that has not been considered as an independent attribute consists of acquisition and maintenance of personal relevant entities such as "familiar" faces, persons, voices, names, linguistic expressions, handwriting, topography, and so on. In experimental studies of normal mentation, personal relevance is revealed in studies of emotion, arousal, affect, preference and familiarity judgments, and memory. Following focal brain damage, deficits and distortions in the experience of personal relevance, as well as in recognizing formerly personally relevant phenomena, are well known to occur. A review and interpretation of these data lead to a proposal that the right hemisphere has a special role in establishing, maintaining, and processing personally relevant aspects of the individual's world.

Man-machine interactive imaging and data processing using high-speed digital mass storage

NASA Technical Reports Server (NTRS)

Alsberg, H.; Nathan, R.

1975-01-01

The role of vision in teleoperation has been recognized as an important element in the man-machine control loop. In most applications of remote manipulation, direct vision cannot be used. To overcome this handicap, the human operator's control capabilities are augmented by a television system. This medium provides a practical and useful link between workspace and the control station from which the operator perform his tasks. Human performance deteriorates when the images are degraded as a result of instrumental and transmission limitations. Image enhancement is used to bring out selected qualities in a picture to increase the perception of the observer. A general purpose digital computer, an extensive special purpose software system is used to perform an almost unlimited repertoire of processing operations.

Anti-liver-kidney microsome antibody type 1 recognizes human cytochrome P450 db1.

PubMed

Gueguen, M; Yamamoto, A M; Bernard, O; Alvarez, F

1989-03-15

Anti-liver-kidney microsome antibody type 1 (LKM1), present in the sera of a group of children with autoimmune hepatitis, was recently shown to recognize a 50 kDa protein identified as rat liver cytochromes P450 db1 and db2. High homology between these two members of the rat P450 IID subfamily and human P450 db1 suggested that anti-LKM1 antibody is directed against this human protein. To test this hypothesis, a human liver cDNA expression library in phage lambda GT-11 was screened using rat P450 db1 cDNA as a probe. Two human cDNA clones were found to be identical to human P450 db1 by restriction mapping. Immunoblot analysis using as antigen, the purified fusion protein from one of the human cDNA clones showed that only anti-LKM1 with anti-50 kDa reactivity recognized the fusion protein. This fusion protein was further used to develop an ELISA test that was shown to be specific for sera of children with this disease. These results: 1) identify the human liver antigen recognized by anti-LKM1 auto-antibodies as cytochrome P450 db1, 2) allow to speculate that mutation on the human P450 db1 gene could alter its expression in the hepatocyte and make it auto-antigenic, 3) provide a simple and specific diagnostic test for this disease.

Creating a monomeric endonuclease TALE-I-SceI with high specificity and low genotoxicity in human cells.

PubMed

Lin, Jianfei; Chen, He; Luo, Ling; Lai, Yongrong; Xie, Wei; Kee, Kehkooi

2015-01-01

To correct a DNA mutation in the human genome for gene therapy, homology-directed repair (HDR) needs to be specific and have the lowest off-target effects to protect the human genome from deleterious mutations. Zinc finger nucleases, transcription activator-like effector nuclease (TALEN) and CRISPR-CAS9 systems have been engineered and used extensively to recognize and modify specific DNA sequences. Although TALEN and CRISPR/CAS9 could induce high levels of HDR in human cells, their genotoxicity was significantly higher. Here, we report the creation of a monomeric endonuclease that can recognize at least 33 bp by fusing the DNA-recognizing domain of TALEN (TALE) to a re-engineered homing endonuclease I-SceI. After sequentially re-engineering I-SceI to recognize 18 bp of the human β-globin sequence, the re-engineered I-SceI induced HDR in human cells. When the re-engineered I-SceI was fused to TALE (TALE-ISVB2), the chimeric endonuclease induced the same HDR rate at the human β-globin gene locus as that induced by TALEN, but significantly reduced genotoxicity. We further demonstrated that TALE-ISVB2 specifically targeted at the β-globin sequence in human hematopoietic stem cells. Therefore, this monomeric endonuclease has the potential to be used in therapeutic gene targeting in human cells. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

Selective cytotoxicity of an oxygen-radical-generating enzyme conjugated to a monoclonal antibody.

PubMed Central

Battelli, M G; Abbondanza, A; Tazzari, P L; Dinota, A; Rizzi, S; Grassi, G; Gobbi, M; Stirpe, F

1988-01-01

The monoclonal antibody 8A, which recognizes a human plasma cell-associated antigen, was covalently linked to xanthine oxidase in a conjugate maintaining both immunological and enzymatic properties. A significant degree of target cell lysis was obtained at an enzyme concentration that was ineffective on non-target cells and on myeloid staminal cells (CFU-GM). The cytotoxic activity was abolished by an excess of antibody, by allopurinol and by superoxide dismutase and catalase. A possible use of the conjugate for bone marrow purging in multiple myeloma patients is suggested. PMID:3262464

Mine Water Treatment in Hongai Coal Mines

NASA Astrophysics Data System (ADS)

Dang, Phuong Thao; Dang, Vu Chi

2018-03-01

Acid mine drainage (AMD) is recognized as one of the most serious environmental problem associated with mining industry. Acid water, also known as acid mine drainage forms when iron sulfide minerals found in the rock of coal seams are exposed to oxidizing conditions in coal mining. Until 2009, mine drainage in Hongai coal mines was not treated, leading to harmful effects on humans, animals and aquatic ecosystem. This report has examined acid mine drainage problem and techniques for acid mine drainage treatment in Hongai coal mines. In addition, selection and criteria for the design of the treatment systems have been presented.

Implausibility of the vibrational theory of olfaction

DOE PAGES

Block, Eric; Ertem, Mehmed Z.; Jang, Seogjoo; ...

2015-04-21

The vibrational theory of olfaction assumes that electron transfer occurs across odorants at the active sites of odorant receptors (ORs), serving as a sensitive measure of odorant vibrational frequencies, ultimately leading to olfactory perception. A previous study reported that human subjects differentiated hydrogen/deuterium isotopomers (isomers with isotopic atoms) of the musk compound cyclopentadecanone as evidence supporting the theory. Here, we find no evidence for such differentiation at the molecular level. In fact, we find that the human musk-recognizing receptor, OR5AN1, identified using a heterologous OR expression system and robustly responding to cyclopentadecanone and muscone, fails to distinguish isotopomers of thesemore » compounds in vitro. Furthermore, the mouse (methylthio)methanethiol (MTMT)-recognizing receptor, MOR244-3, and other selected human and mouse ORs, responded similarly to normal, deuterated, and ¹³C isotopomers of their respective ligands, paralleling our results with the musk receptor OR5AN1. These findings suggest that the proposed vibration theory does not apply to the human musk receptor OR5AN1, mouse thiol receptor MOR244-3, or other ORs examined. Also, contrary to the vibration theory predictions, muscone-d₃₀ lacks the 1,380-1,550 cm⁻¹ IR bands claimed to be essential for musk odor. Furthermore, our theoretical analysis shows that the proposed electron transfer mechanism of the vibrational frequencies of odorants could be easily suppressed by quantum effects of non-odorant molecular vibrational modes. As a result, these and other concerns about electron transfer at ORs, together with our extensive experimental data, argue against the plausibility of the vibration theory.« less

Implausibility of the vibrational theory of olfaction

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

Block, Eric; Ertem, Mehmed Z.; Jang, Seogjoo

The vibrational theory of olfaction assumes that electron transfer occurs across odorants at the active sites of odorant receptors (ORs), serving as a sensitive measure of odorant vibrational frequencies, ultimately leading to olfactory perception. A previous study reported that human subjects differentiated hydrogen/deuterium isotopomers (isomers with isotopic atoms) of the musk compound cyclopentadecanone as evidence supporting the theory. Here, we find no evidence for such differentiation at the molecular level. In fact, we find that the human musk-recognizing receptor, OR5AN1, identified using a heterologous OR expression system and robustly responding to cyclopentadecanone and muscone, fails to distinguish isotopomers of thesemore » compounds in vitro. Furthermore, the mouse (methylthio)methanethiol (MTMT)-recognizing receptor, MOR244-3, and other selected human and mouse ORs, responded similarly to normal, deuterated, and ¹³C isotopomers of their respective ligands, paralleling our results with the musk receptor OR5AN1. These findings suggest that the proposed vibration theory does not apply to the human musk receptor OR5AN1, mouse thiol receptor MOR244-3, or other ORs examined. Also, contrary to the vibration theory predictions, muscone-d₃₀ lacks the 1,380-1,550 cm⁻¹ IR bands claimed to be essential for musk odor. Furthermore, our theoretical analysis shows that the proposed electron transfer mechanism of the vibrational frequencies of odorants could be easily suppressed by quantum effects of non-odorant molecular vibrational modes. As a result, these and other concerns about electron transfer at ORs, together with our extensive experimental data, argue against the plausibility of the vibration theory.« less

How should a speech recognizer work?

PubMed

Scharenborg, Odette; Norris, Dennis; Bosch, Louis; McQueen, James M

2005-11-12

Although researchers studying human speech recognition (HSR) and automatic speech recognition (ASR) share a common interest in how information processing systems (human or machine) recognize spoken language, there is little communication between the two disciplines. We suggest that this lack of communication follows largely from the fact that research in these related fields has focused on the mechanics of how speech can be recognized. In Marr's (1982) terms, emphasis has been on the algorithmic and implementational levels rather than on the computational level. In this article, we provide a computational-level analysis of the task of speech recognition, which reveals the close parallels between research concerned with HSR and ASR. We illustrate this relation by presenting a new computational model of human spoken-word recognition, built using techniques from the field of ASR that, in contrast to current existing models of HSR, recognizes words from real speech input. 2005 Lawrence Erlbaum Associates, Inc.

Communication Aid with Human Eyes Only

NASA Astrophysics Data System (ADS)

Arai, Kohei; Yajima, Kenro

A communication aid with human eyes only is proposed. A set of candidate character is displayed onto computer screen of relatively small and light Head Mount Display: HMD that is mounted on glasses of which user wears on. When user looks at a candidate character with his/hers left eye while right eye picture is taken with small and light web camera that also is mounted on the glasses. The proposed system can selects 81 characters with two layers of 9 by 9 character candidate image. Other than these there is another selective image including control keys and frequently use of sentences. By using image matching between previously acquired template image for each candidate character and the currently acquired image, the proposed system realizes that which character in the candidates is selected. By using blinking and fix one's eye on combine together, the proposed system recognizes that user determines the selected key from the candidates. The blinking detection method employs a morphologic filter to avoid misunderstanding of dark eye detection due to eyebrows and shadows. Thus user can input sentences. User also may edit the sentences and then the sentences are read with Text to Speech: TTS software tool. Thus the system allows support conversations between handicapped and disabled persons without voice and the others peoples because only the function required for conversation is human eyes. Also the proposed system can be used as an input system for wearable computing systems. Test results by the 6 different able persons show that the proposed system does work with acceptable speed, around 1.5 second / character.

A human monoclonal antibody drug and target discovery platform for B-cell chronic lymphocytic leukemia based on allogeneic hematopoietic stem cell transplantation and phage display.

PubMed

Baskar, Sivasubramanian; Suschak, Jessica M; Samija, Ivan; Srinivasan, Ramaprasad; Childs, Richard W; Pavletic, Steven Z; Bishop, Michael R; Rader, Christoph

2009-11-12

Allogeneic hematopoietic stem cell transplantation (alloHSCT) is the only potentially curative treatment available for patients with B-cell chronic lymphocytic leukemia (B-CLL). Here, we show that post-alloHSCT antibody repertoires can be mined for the discovery of fully human monoclonal antibodies to B-CLL cell-surface antigens. Sera collected from B-CLL patients at defined times after alloHSCT showed selective binding to primary B-CLL cells. Pre-alloHSCT sera, donor sera, and control sera were negative. To identify post-alloHSCT serum antibodies and subsequently B-CLL cell-surface antigens they recognize, we generated a human antibody-binding fragment (Fab) library from post-alloHSCT peripheral blood mononuclear cells and selected it on primary B-CLL cells by phage display. A panel of Fab with B-CLL cell-surface reactivity was strongly enriched. Selection was dominated by highly homologous Fab predicted to bind the same antigen. One Fab was converted to immunoglobulin G1 and analyzed for reactivity with peripheral blood mononuclear cells from B-CLL patients and healthy volunteers. Cell-surface antigen expression was restricted to primary B cells and up-regulated in primary B-CLL cells. Mining post-alloHSCT antibody repertoires offers a novel route to discover fully human monoclonal antibodies and identify antigens of potential therapeutic relevance to B-CLL and possibly other cancers. Trials described herein were registered at www.clinicaltrials.gov as nos. NCT00055744 and NCT00003838.

Identification of malaria parasite-infected red blood cell surface aptamers by inertial microfluidic SELEX (I-SELEX)

NASA Astrophysics Data System (ADS)

Birch, Christina M.; Hou, Han Wei; Han, Jongyoon; Niles, Jacquin C.

2015-07-01

Plasmodium falciparum malaria parasites invade and remodel human red blood cells (RBCs) by trafficking parasite-synthesized proteins to the RBC surface. While these proteins mediate interactions with host cells that contribute to disease pathogenesis, the infected RBC surface proteome remains poorly characterized. Here we use a novel strategy (I-SELEX) to discover high affinity aptamers that selectively recognize distinct epitopes uniquely present on parasite-infected RBCs. Based on inertial focusing in spiral microfluidic channels, I-SELEX enables stringent partitioning of cells (efficiency ≥ 106) from unbound oligonucleotides at high volume throughput (~2 × 106 cells min-1). Using an RBC model displaying a single, non-native antigen and live malaria parasite-infected RBCs as targets, we establish suitability of this strategy for de novo aptamer selections. We demonstrate recovery of a diverse set of aptamers that recognize distinct, surface-displayed epitopes on parasite-infected RBCs with nanomolar affinity, including an aptamer against the protein responsible for placental sequestration, var2CSA. These findings validate I-SELEX as a broadly applicable aptamer discovery platform that enables identification of new reagents for mapping the parasite-infected RBC surface proteome at higher molecular resolution to potentially contribute to malaria diagnostics, therapeutics and vaccine efforts.

Health Impacts of Environmental Mycobacteria†

PubMed Central

Primm, Todd P.; Lucero, Christie A.; Falkinham, Joseph O.

2004-01-01

Environmental mycobacteria are emerging pathogens causing opportunistic infections in humans and animals. The health impacts of human-mycobacterial interactions are complex and likely much broader than currently recognized. Environmental mycobacteria preferentially survive chlorination in municipal water, using it as a vector to infect humans. Widespread chlorination of water has likely selected more resistant environmental mycobacteria species and potentially explains the shift from M. scrofulaceum to M. avium as a cause of cervical lymphadenitis in children. Thus, human activities have affected mycobacterial ecology. While the slow growth and hydrophobicity of environmental mycobacteria appear to be disadvantages, the unique cell wall architecture also grants high biocide and antibiotic resistance, while hydrophobicity facilitates nutrient acquisition, biofilm formation, and spread by aerosolization. The remarkable stress tolerance of environmental mycobacteria is the major reason they are human pathogens. Environmental mycobacteria invade protozoans, exhibiting parasitic and symbiotic relationships. The molecular mechanisms of mycobacterial intracellular pathogenesis in animals likely evolved from similar mechanisms facilitating survival in protozoans. In addition to outright infection, environmental mycobacteria may also play a role in chronic bowl diseases, allergies, immunity to other pulmonary infections, and the efficacy of bacillus Calmette-Guerin vaccination. PMID:14726457

Health impacts of environmental mycobacteria.

PubMed

Primm, Todd P; Lucero, Christie A; Falkinham, Joseph O

2004-01-01

Environmental mycobacteria are emerging pathogens causing opportunistic infections in humans and animals. The health impacts of human-mycobacterial interactions are complex and likely much broader than currently recognized. Environmental mycobacteria preferentially survive chlorination in municipal water, using it as a vector to infect humans. Widespread chlorination of water has likely selected more resistant environmental mycobacteria species and potentially explains the shift from M. scrofulaceum to M. avium as a cause of cervical lymphadenitis in children. Thus, human activities have affected mycobacterial ecology. While the slow growth and hydrophobicity of environmental mycobacteria appear to be disadvantages, the unique cell wall architecture also grants high biocide and antibiotic resistance, while hydrophobicity facilitates nutrient acquisition, biofilm formation, and spread by aerosolization. The remarkable stress tolerance of environmental mycobacteria is the major reason they are human pathogens. Environmental mycobacteria invade protozoans, exhibiting parasitic and symbiotic relationships. The molecular mechanisms of mycobacterial intracellular pathogenesis in animals likely evolved from similar mechanisms facilitating survival in protozoans. In addition to outright infection, environmental mycobacteria may also play a role in chronic bowl diseases, allergies, immunity to other pulmonary infections, and the efficacy of bacillus Calmette-Guerin vaccination.

beta. -Adrenoceptors in human tracheal smooth muscle: characteristics of binding and relaxation

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

van Koppen, C.J.; Hermanussen, M.W.; Verrijp, K.N.

1987-06-29

Specific binding of (/sup 125/I)-(-)-cyanopindolol to human tracheal smooth muscle membranes was saturable, stereo-selective and of high affinity (K/sub d/ = 5.3 +/- 0.9 pmol/l and R/sub T/ = 78 +/- 7 fmol/g tissue). The ..beta../sub 1/-selective antagonists atenolol and LK 203-030 inhibited specific (/sup 125/I)-(-)-cyanopindolol binding according to a one binding site model with low affinity in nearly all subjects, pointing to a homogeneous BETA/sub 2/-adrenoceptor population. In one subject using LK 203-030 a small ..beta../sub 1/-adrenoceptor subpopulation could be demonstrated. The beta-mimetics isoprenaline, fenoterol, salbutamol and terbutaline recognized high and low affinity agonist binding sites. Isoprenaline's pK/sub H/-more » and pK/sub L/-values for the high and low affinity sites were 8.0 +/- 0.2 and 5.9 +/- 0.3 respectively. In functional experiments isoprenaline relaxed tracheal smooth muscle strips having intrinsic tone with a pD/sub 2/-value of 6.63 +/- 0.19. 32 references, 4 figures, 2 tables.« less

[Biological and neural bases of partner preferences in rodents: models to understand human pair bonds].

PubMed

Coria-Avila, G A; Hernández-Aguilar, M E; Toledo-Cárdenas, R; García-Hernández, L I; Manzo, J; Pacheco, P; Miquel, M; Pfaus, J G

To analyse the biological and neural bases of partner preference formation in rodents as models to understand human pair bonding. Rodents are social individuals, capable of forming short- or long-lasting partner preferences that develop slowly by stimuli like cohabitation, or rapidly by stimuli like sex and stress. Dopamine, corticosteroids, oxytocin, vasopressin, and opioids form the neurochemical substrate for pair bonding in areas like the nucleus accumbens, the prefrontal cortex, the piriform cortex, the medial preoptic area, the ventral tegmental area and the medial amygdala, among others. Additional areas may participate depending on the nature of the conditioned stimuli by which and individual recognizes a preferred partner. Animal models help us understand that the capacity of an individual to display long-lasting and selective preferences depends on neural bases, selected throughout evolution. The challenge in neuroscience is to use this knowledge to create new solutions for mental problems associated with the incapacity of an individual to display a social bond, keep one, or cope with the disruption of a consolidated one.

Selective suppression of endothelial cytokine production by progesterone receptor.

PubMed

Goddard, Lauren M; Ton, Amy N; Org, Tõnis; Mikkola, Hanna K A; Iruela-Arispe, M Luisa

2013-01-01

Steroid hormones are well-recognized suppressors of the inflammatory response, however, their cell- and tissue-specific effects in the regulation of inflammation are far less understood, particularly for the sex-related steroids. To determine the contribution of progesterone in the endothelium, we have characterized and validated an in vitro culture system in which human umbilical vein endothelial cells constitutively express human progesterone receptor (PR). Using next generation RNA-sequencing, we identified a selective group of cytokines that are suppressed by progesterone both under physiological conditions and during pathological activation by lipopolysaccharide. In particular, IL-6, IL-8, CXCL2/3, and CXCL1 were found to be direct targets of PR, as determined by ChIP-sequencing. Regulation of these cytokines by progesterone was also confirmed by bead-based multiplex cytokine assays and quantitative PCR. These findings provide a novel role for PR in the direct regulation of cytokine levels secreted by the endothelium. They also suggest that progesterone-PR signaling in the endothelium directly impacts leukocyte trafficking in PR-expressing tissues. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

Cloning the Antibody Response in Humans with Chronic Inflammatory Disease: Immunopanning of Subacute Sclerosing Panencephalitis (SSPE) Brain Sections with Antibody Phage Libraries Prepared from SSPE Brain Enriches for Antibody Recognizing Measles Virus Antigens In Situ

PubMed Central

Owens, Gregory P.; Williamson, R. Anthony; Burgoon, Mark P.; Ghausi, Omar; Burton, Dennis R.; Gilden, Donald H.

2000-01-01

In central nervous system (CNS) infectious and inflammatory diseases of known cause, oligoclonal bands represent antibody directed against the causative agent. To determine whether disease-relevant antibodies can be cloned from diseased brain, we prepared an antibody phage display library from the brain of a human with subacute sclerosing panencephalitis (SSPE), a chronic encephalitis caused by measles virus, and selected the library against SSPE brain sections. Antibodies that were retrieved reacted strongly with measles virus cell extracts by enzyme-linked immunosorbent assay and were specific for the measles virus nucleocapsid protein. These antibodies immunostained cells in different SSPE brains but not in control brain. Our data provide the first demonstration that diseased brain can be used to select in situ for antibodies directed against the causative agent of disease and point to the potential usefulness of this approach in identifying relevant antibodies in chronic CNS or systemic inflammatory diseases of unknown cause. PMID:10627565

Application of M13 phage display for identifying immunogenic proteins from tick (Ixodes scapularis) saliva.

PubMed

Becker, Martin; Felsberger, André; Frenzel, André; Shattuck, Wendy M C; Dyer, Megan; Kügler, Jonas; Zantow, Jonas; Mather, Thomas N; Hust, Michael

2015-05-30

Ticks act as vectors for a large number of different pathogens, perhaps most notably Borrelia burgdorferi, the causative agent of Lyme disease. The most prominent tick vector in the United States is the blacklegged tick, Ixodes scapularis. Tick bites are of special public health concern since there are no vaccines available against most tick-transmitted pathogens. Based on the observation that certain non-natural host animals such as guinea pigs or humans can develop adaptive immune responses to tick bites, anti-tick vaccination is a potential approach to tackle health risks associated with tick bites. The aim of this study was to use an oligopeptide phage display strategy to identify immunogenic salivary gland proteins from I. scapularis that are recognized by human immune sera. Oligopeptide libraries were generated from salivary gland mRNA of 18 h fed nymphal I. scapularis. Eight immunogenic oligopeptides were selected using human immune sera. Three selected immunogenic oligopeptides were cloned and produced as recombinant proteins. The immunogenic character of an identified metalloprotease (MP1) was validated with human sera. This enzyme has been described previously and was hypothesized as immunogenic which was confirmed in this study. Interestingly, it also has close homologs in other Ixodes species. An immunogenic protein of I. scapularis was identified by oligopeptide phage display. MP1 is a potential candidate for vaccine development.

Genomic Microbial Epidemiology Is Needed to Comprehend the Global Problem of Antibiotic Resistance and to Improve Pathogen Diagnosis

PubMed Central

Wyrsch, Ethan R.; Roy Chowdhury, Piklu; Chapman, Toni A.; Charles, Ian G.; Hammond, Jeffrey M.; Djordjevic, Steven P.

2016-01-01

Contamination of waste effluent from hospitals and intensive food animal production with antimicrobial residues is an immense global problem. Antimicrobial residues exert selection pressures that influence the acquisition of antimicrobial resistance and virulence genes in diverse microbial populations. Despite these concerns there is only a limited understanding of how antimicrobial residues contribute to the global problem of antimicrobial resistance. Furthermore, rapid detection of emerging bacterial pathogens and strains with resistance to more than one antibiotic class remains a challenge. A comprehensive, sequence-based genomic epidemiological surveillance model that captures essential microbial metadata is needed, both to improve surveillance for antimicrobial resistance and to monitor pathogen evolution. Escherichia coli is an important pathogen causing both intestinal [intestinal pathogenic E. coli (IPEC)] and extraintestinal [extraintestinal pathogenic E. coli (ExPEC)] disease in humans and food animals. ExPEC are the most frequently isolated Gram negative pathogen affecting human health, linked to food production practices and are often resistant to multiple antibiotics. Cattle are a known reservoir of IPEC but they are not recognized as a source of ExPEC that impact human or animal health. In contrast, poultry are a recognized source of multiple antibiotic resistant ExPEC, while swine have received comparatively less attention in this regard. Here, we review what is known about ExPEC in swine and how pig production contributes to the problem of antibiotic resistance. PMID:27379026

Small-Molecule-Based Self-Assembled Ligands for G-Quadruplex DNA Surface Recognition.

PubMed

Rivera-Sánchez, María Del C; García-Arriaga, Marilyn; Hobley, Gerard; Morales-de-Echegaray, Ana V; Rivera, José M

2017-10-31

Most drugs are small molecules because of their attractive pharmacokinetics, manageable development and manufacturing, and effective binding into the concave crevices of bio-macromolecules. Despite these features, they often fall short when it comes to effectively recognizing the surfaces of bio-macromolecules. One way to overcome the challenge of biomolecular surface recognition is to develop small molecules that become self-assembled ligands (SALs) prior to binding. Herein, we report SALs made from 8-aryl-2'-deoxyguanosine derivatives forming precise hydrophilic supramolecular G-quadruplexes (SGQs) with excellent size, shape, and charge complementarity to G-quadruplex DNA (QDNA). We show that only those compounds forming SGQs act as SALs, which in turn differentially stabilize QDNAs from selected oncogene promoters and the human telomeric regions. Fluorescence resonance energy-transfer melting assays are consistent with spectroscopic, calorimetric, and light scattering studies, showing the formation of a "sandwichlike" complex QDNA·SGQ·QDNA. These results open the door for the advent of SALs that recognize QDNAs and potentially the surfaces of other bio-macromolecules such as proteins.

Involvement of HDAC1 and HDAC3 in the Pathology of Polyglutamine Disorders: Therapeutic Implications for Selective HDAC1/HDAC3 Inhibitors

PubMed Central

Thomas, Elizabeth A.

2014-01-01

Histone deacetylases (HDACs) enzymes, which affect the acetylation status of histones and other important cellular proteins, have been recognized as potentially useful therapeutic targets for a broad range of human disorders. Emerging studies have demonstrated that different types of HDAC inhibitors show beneficial effects in various experimental models of neurological disorders. HDAC enzymes comprise a large family of proteins, with18 HDAC enzymes currently identified in humans. Hence, an important question for HDAC inhibitor therapeutics is which HDAC enzyme(s) is/are important for the amelioration of disease phenotypes, as it has become clear that individual HDAC enzymes play different biological roles in the brain. This review will discuss evidence supporting the involvement of HDAC1 and HDAC3 in polyglutamine disorders, including Huntington’s disease, and the use of HDAC1- and HDAC3-selective HDAC inhibitors as therapeutic intervention for these disorders. Further, while HDAC inhibitors are known alter chromatin structure resulting in changes in gene transcription, understanding the exact mechanisms responsible for the preclinical efficacy of these compounds remains a challenge. The potential chromatin-related and non-chromatin-related mechanisms of action of selective HDAC inhibitors will also be discussed. PMID:24865773

Markov State Models Reveal a Two-Step Mechanism of miRNA Loading into the Human Argonaute Protein: Selective Binding followed by Structural Re-arrangement.

PubMed

Jiang, Hanlun; Sheong, Fu Kit; Zhu, Lizhe; Gao, Xin; Bernauer, Julie; Huang, Xuhui

2015-07-01

Argonaute (Ago) proteins and microRNAs (miRNAs) are central components in RNA interference, which is a key cellular mechanism for sequence-specific gene silencing. Despite intensive studies, molecular mechanisms of how Ago recognizes miRNA remain largely elusive. In this study, we propose a two-step mechanism for this molecular recognition: selective binding followed by structural re-arrangement. Our model is based on the results of a combination of Markov State Models (MSMs), large-scale protein-RNA docking, and molecular dynamics (MD) simulations. Using MSMs, we identify an open state of apo human Ago-2 in fast equilibrium with partially open and closed states. Conformations in this open state are distinguished by their largely exposed binding grooves that can geometrically accommodate miRNA as indicated in our protein-RNA docking studies. miRNA may then selectively bind to these open conformations. Upon the initial binding, the complex may perform further structural re-arrangement as shown in our MD simulations and eventually reach the stable binary complex structure. Our results provide novel insights in Ago-miRNA recognition mechanisms and our methodology holds great potential to be widely applied in the studies of other important molecular recognition systems.

Transgenic Parasites Stably Expressing Full-Length Plasmodium falciparum Circumsporozoite Protein as a Model for Vaccine Down-Selection in Mice Using Sterile Protection as an Endpoint

PubMed Central

Porter, Michael D.; Nicki, Jennifer; Pool, Christopher D.; DeBot, Margot; Illam, Ratish M.; Brando, Clara; Bozick, Brooke; De La Vega, Patricia; Angra, Divya; Spaccapelo, Roberta; Crisanti, Andrea; Murphy, Jittawadee R.; Bennett, Jason W.; Schwenk, Robert J.; Ockenhouse, Christian F.

2013-01-01

Circumsporozoite protein (CSP) of Plasmodium falciparum is a protective human malaria vaccine candidate. There is an urgent need for models that can rapidly down-select novel CSP-based vaccine candidates. In the present study, the mouse-mosquito transmission cycle of a transgenic Plasmodium berghei malaria parasite stably expressing a functional full-length P. falciparum CSP was optimized to consistently produce infective sporozoites for protection studies. A minimal sporozoite challenge dose was established, and protection was defined as the absence of blood-stage parasites 14 days after intravenous challenge. The specificity of protection was confirmed by vaccinating mice with multiple CSP constructs of differing lengths and compositions. Constructs that induced high NANP repeat-specific antibody titers in enzyme-linked immunosorbent assays were protective, and the degree of protection was dependent on the antigen dose. There was a positive correlation between antibody avidity and protection. The antibodies in the protected mice recognized the native CSP on the parasites and showed sporozoite invasion inhibitory activity. Passive transfer of anti-CSP antibodies into naive mice also induced protection. Thus, we have demonstrated the utility of a mouse efficacy model to down-select human CSP-based vaccine formulations. PMID:23536694

Rapid electrochemical assessment of tumor suppressor gene methylations in raw human serum, and tumor cells and tissues using immuno-magnetic beads and selective DNA hybridization.

PubMed

Povedano, Eloy; Valverde, Alejandro; Ruiz-Valdepeñas Montiel, Víctor; Pedrero, María; Yáñez-Sedeño, Paloma; Barderas, Rodrigo; San Segundo-Acosta, Pablo; Peláez-García, Alberto; Mendiola, Marta; Hardisson, David; Campuzano, Susana; Pingarron, José Manuel

2018-05-09

We report a rapid and sensitive electrochemical strategy for the detection of gene-specific 5-methylcytosine DNA methylation. Magnetic beads (MBs) modified with an antibody specific for 5-methylcytosines (5-mC) are employed for the selective capture of any 5-mC methylated single-stranded (ss)DNA sequence. A flanking region next to the 5-mCs of the captured methylated ssDNA is recognized by selective hybridization with a synthetic biotinylated DNA sequence, further labeled with an HRP streptavidin conjugate. Amperometric transduction at disposable screen-printed carbon electrodes (SPCEs) is employed. The developed biosensor exhibits a dynamic range from 3.9 to 500 pM and a detection limit of 1.2 pM for the methylated synthetic sequence of the tumor suppressor gene O-6-methylguanine-DNA methyltransferase (MGMT) promoter region. The applicability of this strategy is demonstrated through the 45 min-analysis of specific methylation in the MGMT promoter region directly in raw spiked human serum samples and in genomic DNA extracted from U-87 glioblastoma cells and paraffin-embedded brain tumor tissues without any amplification and pretreatment step. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Connotative Meaning of Military Chat Communications

DTIC Science & Technology

2009-09-01

humans recognize connotative cues expressing uncertainty, perception of personal threat, and urgency; formulate linguistic and non-linguistic means for...built a matrix of speech “cues” representative of uncertainty, perception of personal threat, and urgency, but also applied maximum entropy analysis...results. This project proposed to: (1) conduct a study of how humans recognize connotative cues expressing uncertainty, perception of personal

Hybrid Synthetic Receptors on MOSFET Devices for Detection of Prostate Specific Antigen in Human Plasma.

PubMed

Tamboli, Vibha K; Bhalla, Nikhil; Jolly, Pawan; Bowen, Chris R; Taylor, John T; Bowen, Jenna L; Allender, Chris J; Estrela, Pedro

2016-12-06

The study reports the use of extended gate field-effect transistors (FET) for the label-free and sensitive detection of prostate cancer (PCa) biomarkers in human plasma. The approach integrates for the first time hybrid synthetic receptors comprising of highly selective aptamer-lined pockets (apta-MIP) with FETs for sensitive detection of prostate specific antigen (PSA) at clinically relevant concentrations. The hybrid synthetic receptors were constructed by immobilizing an aptamer-PSA complex on gold and subjecting it to 13 cycles of dopamine electropolymerization. The polymerization resulted in the creation of highly selective polymeric cavities that retained the ability to recognize PSA post removal of the protein. The hybrid synthetic receptors were subsequently used in an extended gate FET setup for electrochemical detection of PSA. The sensor was reported to have a limit of detection of 0.1 pg/mL with a linear detection range from 0.1 pg/mL to 1 ng/mL PSA. Detection of 1-10 pg/mL PSA was also achieved in diluted human plasma. The present apta-MIP sensor developed in conjunction with FET devices demonstrates the potential for clinical application of synthetic hybrid receptors for the detection of clinically relevant biomarkers in complex samples.

Olfactory cues associated with the major histocompatibility complex.

PubMed

Eggert, F; Müller-Ruchholtz, W; Ferstl, R

Besides its immunological function of self/non-self discrimination the major histocompatibility complex (MHC) has been recognized as a possible source of individual specific body odors. Dating back to speculations on the role of the extraordinary polymorphism of the MHC as background of an individual chemosensory identity and to early observations of MHC-dependent mate choice in inbred strains of mice, systematic experimental studies revealed a first evidence for H-2 related body odors in this species. Meanwhile a large number of animal studies with rodents and a series of field studies and experiments with humans have extended our knowledge of MHC-related odor signals and substantiated the hypothesis of immunogenetic associated odor types. These results suggest that the most prominent feature of the MHC, its extraordinary genetic diversity, seems in part to be selectively maintained by behavioral mechanisms which operate in contemporary natural populations. The high degree of heterozygosity found in natural populations of most species seems to be promoted by non-disease-based selection such as mating preferences and selective block of pregnancy.

Selection of a novel CD19 aptamer for targeted delivery of doxorubicin to lymphoma cells.

PubMed

Hu, Yan; Li, Xiaoou; An, Yacong; Duan, Jinhong; Yang, Xian-Da

2018-06-01

CD19 is overexpressed in most human B cell malignancies and considered an important tumor marker for diagnosis and treatment. Aptamers are oligonucleotides that may potentially serve as tumor-homing ligand for targeted cancer therapy with excellent affinity and specificity. In this study, we selected a novel CD19 aptamer (LC1) that was a 59-nucleotide single strand DNA. The aptamer could bind to recombinant CD19 protein with a K d of 85.4 nM, and had minimal cross reactivity to bovine serum albumin (BSA) or ovalbumin (OVA). Moreover, the aptamer was found capable of binding with the CD19-positive lymphoma cells (Ramos and Raji), but not the CD19-negative cell lines (Jurkat and NB4). An aptamer-doxorubicin complex (Apt-Dox) was also formulated, and selectively delivered doxorubicin to CD19-positive lymphoma cells in vitro . The results indicate that aptamer LC1 can recognize CD19-positive tumor cells and may potentially function as a CD19-targeting ligand.

ABCG2 Is a Selectable Marker for Enhanced Multilineage Differentiation Potential in Periodontal Ligament Stem Cells

PubMed Central

Szepesi, Áron; Matula, Zsolt; Szigeti, Anna; Várady, György; Szabó, Gyula; Uher, Ferenc; Sarkadi, Balázs

2015-01-01

Periodontal ligament stem cells (PDLSCs) provide an important source for tissue regeneration and may become especially useful in the formation of osteogenic seeds. PDLSCs can be cultured, expanded, and differentiated in vitro; thus, they may be applied in the long-term treatment of the defects in the dental regions. Here we studied numerous potential markers allowing the selection of human PDLSCs with a maximum differentiation potential. We followed the expression of the ATP-binding cassette subfamily G member 2 (ABCG2) membrane transporter protein and isolated ABCG2-expressing cells by using a monoclonal antibody, recognizing the transporter at the cell surface in intact cells. The expression of the ABCG2 protein, corresponding to the so-called side-population phenotype in various tissue-derived stem cells, was found to be a useful marker for the selection of PDLSCs with enhanced osteogenic, chondrogenic, and adipogenic differentiation. These findings may have important applications in achieving efficient dental tissue regeneration by using stem cells from extracted teeth. PMID:25101689

Mathematical algorithm for the automatic recognition of intestinal parasites.

PubMed

Alva, Alicia; Cangalaya, Carla; Quiliano, Miguel; Krebs, Casey; Gilman, Robert H; Sheen, Patricia; Zimic, Mirko

2017-01-01

Parasitic infections are generally diagnosed by professionals trained to recognize the morphological characteristics of the eggs in microscopic images of fecal smears. However, this laboratory diagnosis requires medical specialists which are lacking in many of the areas where these infections are most prevalent. In response to this public health issue, we developed a software based on pattern recognition analysis from microscopi digital images of fecal smears, capable of automatically recognizing and diagnosing common human intestinal parasites. To this end, we selected 229, 124, 217, and 229 objects from microscopic images of fecal smears positive for Taenia sp., Trichuris trichiura, Diphyllobothrium latum, and Fasciola hepatica, respectively. Representative photographs were selected by a parasitologist. We then implemented our algorithm in the open source program SCILAB. The algorithm processes the image by first converting to gray-scale, then applies a fourteen step filtering process, and produces a skeletonized and tri-colored image. The features extracted fall into two general categories: geometric characteristics and brightness descriptions. Individual characteristics were quantified and evaluated with a logistic regression to model their ability to correctly identify each parasite separately. Subsequently, all algorithms were evaluated for false positive cross reactivity with the other parasites studied, excepting Taenia sp. which shares very few morphological characteristics with the others. The principal result showed that our algorithm reached sensitivities between 99.10%-100% and specificities between 98.13%- 98.38% to detect each parasite separately. We did not find any cross-positivity in the algorithms for the three parasites evaluated. In conclusion, the results demonstrated the capacity of our computer algorithm to automatically recognize and diagnose Taenia sp., Trichuris trichiura, Diphyllobothrium latum, and Fasciola hepatica with a high sensitivity and specificity.

Mathematical algorithm for the automatic recognition of intestinal parasites

PubMed Central

Alva, Alicia; Cangalaya, Carla; Quiliano, Miguel; Krebs, Casey; Gilman, Robert H.; Sheen, Patricia; Zimic, Mirko

2017-01-01

Parasitic infections are generally diagnosed by professionals trained to recognize the morphological characteristics of the eggs in microscopic images of fecal smears. However, this laboratory diagnosis requires medical specialists which are lacking in many of the areas where these infections are most prevalent. In response to this public health issue, we developed a software based on pattern recognition analysis from microscopi digital images of fecal smears, capable of automatically recognizing and diagnosing common human intestinal parasites. To this end, we selected 229, 124, 217, and 229 objects from microscopic images of fecal smears positive for Taenia sp., Trichuris trichiura, Diphyllobothrium latum, and Fasciola hepatica, respectively. Representative photographs were selected by a parasitologist. We then implemented our algorithm in the open source program SCILAB. The algorithm processes the image by first converting to gray-scale, then applies a fourteen step filtering process, and produces a skeletonized and tri-colored image. The features extracted fall into two general categories: geometric characteristics and brightness descriptions. Individual characteristics were quantified and evaluated with a logistic regression to model their ability to correctly identify each parasite separately. Subsequently, all algorithms were evaluated for false positive cross reactivity with the other parasites studied, excepting Taenia sp. which shares very few morphological characteristics with the others. The principal result showed that our algorithm reached sensitivities between 99.10%-100% and specificities between 98.13%- 98.38% to detect each parasite separately. We did not find any cross-positivity in the algorithms for the three parasites evaluated. In conclusion, the results demonstrated the capacity of our computer algorithm to automatically recognize and diagnose Taenia sp., Trichuris trichiura, Diphyllobothrium latum, and Fasciola hepatica with a high sensitivity and specificity. PMID:28410387

Preserved Haptic Shape Processing after Bilateral LOC Lesions.

PubMed

Snow, Jacqueline C; Goodale, Melvyn A; Culham, Jody C

2015-10-07

The visual and haptic perceptual systems are understood to share a common neural representation of object shape. A region thought to be critical for recognizing visual and haptic shape information is the lateral occipital complex (LOC). We investigated whether LOC is essential for haptic shape recognition in humans by studying behavioral responses and brain activation for haptically explored objects in a patient (M.C.) with bilateral lesions of the occipitotemporal cortex, including LOC. Despite severe deficits in recognizing objects using vision, M.C. was able to accurately recognize objects via touch. M.C.'s psychophysical response profile to haptically explored shapes was also indistinguishable from controls. Using fMRI, M.C. showed no object-selective visual or haptic responses in LOC, but her pattern of haptic activation in other brain regions was remarkably similar to healthy controls. Although LOC is routinely active during visual and haptic shape recognition tasks, it is not essential for haptic recognition of object shape. The lateral occipital complex (LOC) is a brain region regarded to be critical for recognizing object shape, both in vision and in touch. However, causal evidence linking LOC with haptic shape processing is lacking. We studied recognition performance, psychophysical sensitivity, and brain response to touched objects, in a patient (M.C.) with extensive lesions involving LOC bilaterally. Despite being severely impaired in visual shape recognition, M.C. was able to identify objects via touch and she showed normal sensitivity to a haptic shape illusion. M.C.'s brain response to touched objects in areas of undamaged cortex was also very similar to that observed in neurologically healthy controls. These results demonstrate that LOC is not necessary for recognizing objects via touch. Copyright © 2015 the authors 0270-6474/15/3513745-16$15.00/0.

Ghost-in-the-Machine reveals human social signals for human-robot interaction.

PubMed

Loth, Sebastian; Jettka, Katharina; Giuliani, Manuel; de Ruiter, Jan P

2015-01-01

We used a new method called "Ghost-in-the-Machine" (GiM) to investigate social interactions with a robotic bartender taking orders for drinks and serving them. Using the GiM paradigm allowed us to identify how human participants recognize the intentions of customers on the basis of the output of the robotic recognizers. Specifically, we measured which recognizer modalities (e.g., speech, the distance to the bar) were relevant at different stages of the interaction. This provided insights into human social behavior necessary for the development of socially competent robots. When initiating the drink-order interaction, the most important recognizers were those based on computer vision. When drink orders were being placed, however, the most important information source was the speech recognition. Interestingly, the participants used only a subset of the available information, focussing only on a few relevant recognizers while ignoring others. This reduced the risk of acting on erroneous sensor data and enabled them to complete service interactions more swiftly than a robot using all available sensor data. We also investigated socially appropriate response strategies. In their responses, the participants preferred to use the same modality as the customer's requests, e.g., they tended to respond verbally to verbal requests. Also, they added redundancy to their responses, for instance by using echo questions. We argue that incorporating the social strategies discovered with the GiM paradigm in multimodal grammars of human-robot interactions improves the robustness and the ease-of-use of these interactions, and therefore provides a smoother user experience.

An immunoglobulin M monoclonal antibody, recognizing a subset of acetylcholinesterase molecules from electric organs of Electrophorus and Torpedo, belongs to the HNK-1 anti-carbohydrate family.

PubMed

Bon, S; Méflah, K; Musset, F; Grassi, J; Massoulié, J

1987-12-01

An immunoglobulin M (IgM) monoclonal antibody (mAb Elec-39), obtained against asymmetric acetylcholinesterase (AChE) from Electrophorus electric organs, also reacts with a fraction of globular AChE (amphiphilic G2 form) from Torpedo electric organs. This antibody does not react with asymmetric AChE from Torpedo electric organs or with the enzyme from other tissues of Electrophorus or Torpedo. The corresponding epitope is removed by endoglycosidase F, showing that it is a carbohydrate. The subsets of Torpedo G2 that react or do not react with Elec-39 (Elec-39+ and Elec-39-) differ in their electrophoretic mobility under nondenaturing conditions; the Elec-39+ component also binds the lectins from Pisum sativum and Lens culinaris. Whereas the Elec-39- component is present at the earliest developmental stages examined, an Elec-39+ component becomes distinguishable only around the 70-mm stage. Its proportion increases progressively, but later than the rapid accumulation of the total G2 form. In immunoblots, mAb Elec-39 recognizes a number of proteins other than AChE from various tissues of several species. The specificity of Elec-39 resembles that of a family of anti-carbohydrate antibodies that includes HNK-1, L2, NC-1, NSP-4, as well as IgMs that occur in human neuropathies. Although some human neuropathy IgMs that recognize the myelin-associated glycoprotein did not react with Elec-39+ AChE, mAbs HNK-1, NC-1, and NSP-4 showed the same selectivity as Elec-39 for Torpedo G2 AChE, but differed in the formation of immune complexes.

Human recombinant Fab fragment from combinatorial libraries of a B-cell lymphoma patient recognizes core protein of chondroitin sulphate proteoglycan 4.

PubMed

Egami, Yoko; Narushima, Yuta; Ohshima, Motohiro; Yoshida, Akira; Yoneta, Naruki; Masaki, Yasufumi; Itoh, Kunihiko

2018-01-01

CD antigens are well known as therapeutic targets of B-cell lymphoma. To isolate therapeutic antibodies that recognize novel targets other than CD antigens, we constructed a phage display combinatorial antibody Fab library from bone marrow lymphocytes of B-cell lymphoma patient. To eliminate antibodies reactive with known B-cell lymphoma antigen, non-hematopoietic and patient's sera reactive HeLaS3 cells was selected as a target of whole cell panning. Five rounds of panning against live HeLaS3 cells retrieved single Fab clone, termed AHSA (Antibody to HeLa Surface Antigen). Using phage display random peptide library, LSYLEP was identified as an epitope sequence of AHSA. LC-MS/MS analysis of AHSA-precipitated HeLaS3 cell lysates detected several fragments corresponding to the sequence of chondroitin sulphate proteoglycan 4 (CSPG4) core protein. Since LSYLEP sequence was at the position of 313-318 of CSPG4, we considered that CSPG4 was AHSA-associated antigen. Double staining of CSPG4-postive MDA-MB-435S cells with AHSA and anti-CSPG4 rabbit antibody showed identical staining position, and reduced AHSA reactivity was observed in CSPG4-siRNA treated MDA-MB-435S cells. In conclusion, we retrieved a human Fab from antibody library of B-cell lymphoma patient, and identified CSPG4 as a recognizing antigen. AHSA may have potential benefits for development of CSPG4-targeting theranostics for B-cell lymphoma. © The Authors 2017. Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved.

Allergy prevention by breastfeeding: possible mechanisms and evidence from human cohorts.

PubMed

Munblit, Daniel; Verhasselt, Valérie

2016-10-01

Allergy is a modern disease which does not seem to benefit from breast milk preventive effects. We propose that maternal milk composition has not adapted to the needs of allergy prevention because of the recent and rapid increase of allergy. Modulation of breast milk composition may be the best strategy to counteract allergy development. We will review recent advances in understanding of allergy physiopathology and how breast milk factors may be specifically appropriate to interfere with allergy development in early life. There is strong evidence both from rodent and human studies that breast milk factors may impact on parameters which are now recognized to be essential for allergy physiopathology: infant gut barrier function, microbiota metabolites production, and oral tolerance induction. Data from human cohorts support the possibility to modify breast milk composition by selected interventions and to impact health outcomes in offspring. Nutritional intervention in lactating mothers should endow breast milk with the capacity to combat allergy epidemics in addition to infectious disease.

Differentiation and Glucocorticoid Regulated Apopto-Phagocytic Gene Expression Patterns in Human Macrophages. Role of Mertk in Enhanced Phagocytosis

PubMed Central

Zahuczky, Gábor; Kristóf, Endre; Majai, Gyöngyike; Fésüs, László

2011-01-01

The daily clearance of physiologically dying cells is performed safely mainly by cells in the mononuclear phagocyte system. They can recognize and engulf dying cells utilizing several cooperative mechanisms. In our study we show that the expression of a broad range of apopto-phagocytic genes is strongly up-regulated during differentiation of human monocytes to macrophages with different donor variability. The glucocorticoid dexamethasone has a profound effect on this process by selectively up-regulating six genes and down-regulating several others. The key role of the up-regulated mer tyrosine kinase (Mertk) in dexamethasone induced enhancement of phagocytosis could be demonstrated in human monocyte derived macrophages by gene silencing as well as blocking antibodies, and also in a monocyte-macrophage like cell line. However, the additional role of other glucocorticoid induced elements must be also considered since the presence of autologous serum during phagocytosis could almost completely compensate for the blocked function of Mertk. PMID:21731712

European bats as carriers of viruses with zoonotic potential.

PubMed

Kohl, Claudia; Kurth, Andreas

2014-08-13

Bats are being increasingly recognized as reservoir hosts of highly pathogenic and zoonotic emerging viruses (Marburg virus, Nipah virus, Hendra virus, Rabies virus, and coronaviruses). While numerous studies have focused on the mentioned highly human-pathogenic bat viruses in tropical regions, little is known on similar human-pathogenic viruses that may be present in European bats. Although novel viruses are being detected, their zoonotic potential remains unclear unless further studies are conducted. At present, it is assumed that the risk posed by bats to the general public is rather low. In this review, selected viruses detected and isolated in Europe are discussed from our point of view in regard to their human-pathogenic potential. All European bat species and their roosts are legally protected and some European species are even endangered. Nevertheless, the increasing public fear of bats and their viruses is an obstacle to their protection. Educating the public regarding bat lyssaviruses might result in reduced threats to both the public and the bats.

FLB1, a human protein of epididymal origin that is involved in the sperm-oocyte recognition process.

PubMed

Boué, F; Duquenne, C; Lassalle, B; Lefèvre, A; Finaz, C

1995-02-01

CA6 antibody was selected out of a monoclonal antibody library raised against human sperm proteins primarily for its ability to recognize an epididymal antigen and to modify sperm adhesion to zona-free hamster oocytes. In the present study, CA6 was shown to decrease sperm binding to zona-free hamster and human oocytes by 40-92% and 38-48%, respectively. The corresponding protein, which was referred to as FLB1, was found to be secreted by the epididymis and to bind specifically to a human, macaque, and rodent subacrosomal sperm region. Western blotting revealed a molecular mass of 94 kDa in human epididymal extracts and of 100 kDa in human, macaque, mouse, rat, and hamster sperm, suggesting further modifications after its binding to sperm. An equivalent protein was not observed in human liver, ovary, testis, plasma, or epidermis. Two-dimensional electrophoresis showed that FLB1 is formed of two subunits with the same 47-kDa molecular mass and slightly different pI (5.8, 5.9). Microsequencing of the protein revealed a partial homology with human cytokeratins 1 and 10. These results suggest that FLB1 is an epididymis-specific cytokeratin-like protein that is involved in the sperm-oocyte recognition process.

Engineering of Bispecific Affinity Proteins with High Affinity for ERBB2 and Adaptable Binding to Albumin

PubMed Central

Nilvebrant, Johan; Åstrand, Mikael; Georgieva-Kotseva, Maria; Björnmalm, Mattias; Löfblom, John; Hober, Sophia

2014-01-01

The epidermal growth factor receptor 2, ERBB2, is a well-validated target for cancer diagnostics and therapy. Recent studies suggest that the over-expression of this receptor in various cancers might also be exploited for antibody-based payload delivery, e.g. antibody drug conjugates. In such strategies, the full-length antibody format is probably not required for therapeutic effect and smaller tumor-specific affinity proteins might be an alternative. However, small proteins and peptides generally suffer from fast excretion through the kidneys, and thereby require frequent administration in order to maintain a therapeutic concentration. In an attempt aimed at combining ERBB2-targeting with antibody-like pharmacokinetic properties in a small protein format, we have engineered bispecific ERBB2-binding proteins that are based on a small albumin-binding domain. Phage display selection against ERBB2 was used for identification of a lead candidate, followed by affinity maturation using second-generation libraries. Cell surface display and flow-cytometric sorting allowed stringent selection of top candidates from pools pre-enriched by phage display. Several affinity-matured molecules were shown to bind human ERBB2 with sub-nanomolar affinity while retaining the interaction with human serum albumin. Moreover, parallel selections against ERBB2 in the presence of human serum albumin identified several amino acid substitutions that dramatically modulate the albumin affinity, which could provide a convenient means to control the pharmacokinetics. The new affinity proteins competed for ERBB2-binding with the monoclonal antibody trastuzumab and recognized the native receptor on a human cancer cell line. Hence, high affinity tumor targeting and tunable albumin binding were combined in one small adaptable protein. PMID:25089830

NREL Scientist Selected for Major Award by the American Chemical Society

Science.gov Websites

Chemistry. The award recognizes his many research, teaching, writing and administrative accomplishments recognized surface scientist, Czanderna has educated thousands through his teaching and writing. He is an

Definition of the Cattle Killer Cell Ig–like Receptor Gene Family: Comparison with Aurochs and Human Counterparts

PubMed Central

Sanderson, Nicholas D.; Norman, Paul J.; Guethlein, Lisbeth A.; Ellis, Shirley A.; Williams, Christina; Breen, Matthew; Park, Steven D. E.; Magee, David A.; Babrzadeh, Farbod; Warry, Andrew; Watson, Mick; Bradley, Daniel G.; MacHugh, David E.; Parham, Peter

2014-01-01

Under selection pressure from pathogens, variable NK cell receptors that recognize polymorphic MHC class I evolved convergently in different species of placental mammal. Unexpectedly, diversified killer cell Ig–like receptors (KIRs) are shared by simian primates, including humans, and cattle, but not by other species. Whereas much is known of human KIR genetics and genomics, knowledge of cattle KIR is limited to nine cDNA sequences. To facilitate comparison of the cattle and human KIR gene families, we determined the genomic location, structure, and sequence of two cattle KIR haplotypes and defined KIR sequences of aurochs, the extinct wild ancestor of domestic cattle. Larger than its human counterpart, the cattle KIR locus evolved through successive duplications of a block containing ancestral KIR3DL and KIR3DX genes that existed before placental mammals. Comparison of two cattle KIR haplotypes and aurochs KIR show the KIR are polymorphic and the gene organization and content appear conserved. Of 18 genes, 8 are functional and 10 were inactivated by point mutation. Selective inactivation of KIR3DL and activating receptor genes leaves a functional cohort of one inhibitory KIR3DL, one activating KIR3DX, and six inhibitory KIR3DX. Functional KIR diversity evolved from KIR3DX in cattle and from KIR3DL in simian primates. Although independently evolved, cattle and human KIR gene families share important function-related properties, indicating that cattle KIR are NK cell receptors for cattle MHC class I. Combinations of KIR and MHC class I are the major genetic factors associated with human disease and merit investigation in cattle. PMID:25398326

Factors Shaping the Human Exposome in the Built Environment: Opportunities for Engineering Control.

PubMed

Dai, Dongjuan; Prussin, Aaron J; Marr, Linsey C; Vikesland, Peter J; Edwards, Marc A; Pruden, Amy

2017-07-18

The "exposome" is a term describing the summation of one's lifetime exposure to microbes and chemicals. Such exposures are now recognized as major drivers of human health and disease. Because humans spend ∼90% of their time indoors, the built environment exposome merits particular attention. Herein we utilize an engineering perspective to advance understanding of the factors that shape the built environment exposome and its influence on human wellness and disease, while simultaneously informing development of a framework for intentionally controlling the exposome to protect public health. Historically, engineers have been focused on controlling chemical and physical contaminants and on eradicating microbes; however, there is a growing awareness of the role of "beneficial" microbes. Here we consider the potential to selectively control the materials and chemistry of the built environment to positively influence the microbial and chemical components of the indoor exposome. Finally, we discuss research gaps that must be addressed to enable intentional engineering design, including the need to define a "healthy" built environment exposome and how to control it.

Taking the social origins of human nature seriously: toward a more imperialist social psychology.

PubMed

Brewer, Marilynn B

2004-01-01

To recognize that human beings are adapted for social living is fundamental to the science of human psychology. I argue that the development of broad social psychological theory would benefit from taking this basic premise more seriously. We need to pay more attention to the implications for personality and social psychology of recognizing that all of the building blocks of human psychology--cognition, emotion, motivation--have been shaped by the demands of social interdependence. In this article I illustrate the generative potential of this basic premise for development of more expansive social theory.

Does medical student membership in the gold humanism honor society influence selection for residency?

PubMed

Rosenthal, Susan; Howard, Brian; Schlussel, Yvette R; Lazarus, Cathy J; Wong, Jeffrey G; Moutier, Christine; Savoia, Maria; Trooskin, Stanley; Wagoner, Norma

2009-01-01

With the creation of the Gold Humanism Honor Society (GHHS) in 2002, the Arnold P. Gold Foundation established a mechanism for recognizing medical students who demonstrate exemplary humanism/professionalism/communication skills. Currently, 80 medical schools have GHHS chapters. Selection is based on peer nomination using a validated tool. The objective of this survey was to assess the percentage of residency program directors (PDs) who are aware of and are using GHHS membership as a residency selection tool. Surgery (SURG) and internal medicine (IM) PDs in 4 United States regions were surveyed for familiarity with GHHS and perceived rank of GHHS membership relative to Alpha Omega Alpha (AOA) membership, class rank, medical student performance evaluation (MSPE), clerkship grade, and United States Medical Licensing Examination (USMLE) score, in evaluating an applicant's humanism/professionalism, service orientation, and fit with their program. Program demographics and familiarity with GHHS were also surveyed. The response rate was 56% (149 respondents). IM PDs rated GHHS membership higher than did SURG PDs when evaluating professionalism/humanism and service orientation. PDs familiar with GHHS ranked membership higher when considering professionalism/humanism (4.1 vs 3.2; p < 0.05) and service orientation (4.1 vs 2.9; p < 0.01). Familiarity with GHHS correlated with being an IM PD, residency based at teaching hospital, large residency program, knowledge of residents who were GHHS members, and having a GHHS chapter at their school (p < 0.01). Familiarity with GHHS was related to rankings of GHHS (professionalism/humanism F = 3.36; p < 0.05; service orientation F = 3.86; p < 0.05) more than the PDs' specialty was. In all, 157 GHHS students (from all 4 United States regions) were also surveyed about the 1197 interviews they had with residency PDs. They reported that although a few PDs were aware of GHHS, PDs of core medical specialties were more aware of GHHS than SURG PDs. IM PDs were more aware of GHHS (70%) than SURG PDs (30%). Awareness was related to the favorable ranking of GHHS as a selection criterion for humanism/professionalism/service orientation. PDs familiar with GHHS were from larger programs, were likely to know residents who were members, and were likely to think that GHHS membership predicted humanistic care. Membership in GHHS may set candidates apart from their peers and allow PDs to distinguish objectively the candidates who demonstrate compassionate medical care. Increased knowledge about the GHHS may therefore serve to be a useful adjunct for PDs when selecting medical students for their residency programs.

Characterization of antibodies that selectively detect alpha-synuclein in pathological inclusions.

PubMed

Waxman, Elisa A; Duda, John E; Giasson, Benoit I

2008-07-01

Sensitive detection of alpha-synuclein (alpha-syn) pathology is important in the diagnosis of disorders like Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy and in providing better insights into the etiology of these diseases. Several monoclonal antibodies that selectively react with aggregated alpha-syn in pathological inclusions and reveal extensive and underappreciated alpha-syn pathology in the brains of diseased patients were previously reported by Duda et al. (Ann Neurol 52:205-210, 2002). We sought to characterize the specificity of some of these antibodies (Syn 505, Syn 506 and Syn 514); using C-terminal and N-terminal truncations of alpha-syn, all three antibodies were determined to require N-terminal epitopes that minimally comprise amino acids 2-4, but possibly extend to amino acid 12 of alpha-syn. The selectivity of these antibodies was further assessed using biochemical analysis of human brains and reactivity to altered recombinant alpha-syn proteins with duplication variants of amino acids 1-12. In addition, by expressing wild-type or a double mutant (E46K/A53T) of alpha-syn in cultured cells and by comparing their immunoreactivities to another antibody (SNL-4), which has a similar primary epitope, it was determined that Syn 505, Syn 506 and Syn 514 recognize conformational variants of alpha-syn that is enhanced by the presence of the double mutations. These studies indicate that antibodies Syn 505, Syn 506 and Syn 514 preferentially recognize N-terminal epitopes in complex conformations, consistent with the dramatic conformational change associated with the polymerization of alpha-synuclein into amyloid fibrils that form pathological inclusions.

Enzyme-linked immunosorbent assay for detection of organophosphorylated butyrylcholinesterase: A biomarker of exposure to organophosphate agents

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

Wang, Liming; Du, Dan; Lu, Donglai

2011-05-05

A sandwich enzyme-linked immunosorbent assay (sELISA) is developed for detection of organophosphorylated butyrylcholinesterase (OP-BChE), a potential biomarker for human exposure to organophosphate insecticides and nerve agents. A pair of antibodies specific to OP-BChE adduct were identified through systematic screening of several anti BChE antibodies (anti-BChE) and anti-phosphoserine antibodies (anti-Pser) from different sources. The selected anti-BChE (set as capture antibody) antibodies recognize both phosphorylated and nonphosphorylated BChE. These antibodies can therefore be used to capture both BChE and OP-BChE from the sample matrices. The anti- Pser (set as detecting antibody) was used to recognize the OP moiety of OP-BChE adducts. Withmore » the combination of the selected antibody pair, several key parameters (such as the concentration of anti-BChE and anti-Pser, and the blocking agent) were optimized to enhance the sensitivity and selectivity of the sELISA. Under the optimal conditions, the sELISA has shown a wide linear range from 0.03 nM to 30 nM, with a detection limit of 0.03 nM. Furthermore, the sELISA was successfully applied to detect OP-BChE using in-vitro biological samples such as rat plasma spiked with OP-BChE with excellent adduct recovery (z>99 %). These results demonstrate that this novel approach holds great promise to develop an ELISA kit and offers a simple and cost-effective tool for screening/evaluating exposure to organophosphate insecticides and nerve agents.« less

Three human chromosomal autoantigens are recognized by sera from patients with anti-centromere antibodies.

PubMed Central

Earnshaw, W; Bordwell, B; Marino, C; Rothfield, N

1986-01-01

We have identified 39 individuals with anti-centromere antibodies (ACA) in our patient population, all of whom have Raynaud's syndrome or disease. We have used sera from the ACA-positive patients and from 123 controls (22 normal individuals and 101 additional patients with either Raynaud's disease or Raynaud's syndrome plus an associated connective tissue disease) to screen the proteins of highly purified human (HeLa) mitotic chromosomes by sodium dodecyl sulfate polyacrylamide gel electrophoresis and immunoblotting. Three antigens were recognized by the sera from the ACA-positive patients. These were centromere protein (CENP)-B (80,000 mol wt--recognized by all ACA-positive sera), CENP-A (17,000 mol wt--recognized by 38 of 39 ACA-positive sera), and CENP-C (140,000 mol wt--recognized by 37 of 39 ACA-positive sera). None of these antigens were recognized by any of the 123 control sera, although binding was occasionally seen to other chromosomal antigens. Therefore the ACA response is highly uniform in our patient population. Antibody to CENP-B shows a 100% correlation with anti-centromere staining by indirect immunofluorescence. Images PMID:3511098

Three human chromosomal autoantigens are recognized by sera from patients with anti-centromere antibodies.

PubMed

Earnshaw, W; Bordwell, B; Marino, C; Rothfield, N

1986-02-01

We have identified 39 individuals with anti-centromere antibodies (ACA) in our patient population, all of whom have Raynaud's syndrome or disease. We have used sera from the ACA-positive patients and from 123 controls (22 normal individuals and 101 additional patients with either Raynaud's disease or Raynaud's syndrome plus an associated connective tissue disease) to screen the proteins of highly purified human (HeLa) mitotic chromosomes by sodium dodecyl sulfate polyacrylamide gel electrophoresis and immunoblotting. Three antigens were recognized by the sera from the ACA-positive patients. These were centromere protein (CENP)-B (80,000 mol wt--recognized by all ACA-positive sera), CENP-A (17,000 mol wt--recognized by 38 of 39 ACA-positive sera), and CENP-C (140,000 mol wt--recognized by 37 of 39 ACA-positive sera). None of these antigens were recognized by any of the 123 control sera, although binding was occasionally seen to other chromosomal antigens. Therefore the ACA response is highly uniform in our patient population. Antibody to CENP-B shows a 100% correlation with anti-centromere staining by indirect immunofluorescence.

In vitro selection of RNA aptamer specific to Salmonella typhimurium.

PubMed

Han, Seung Ryul; Lee, Seong-Wook

2013-06-28

Salmonella is a major foodborne pathogen that causes a variety of human diseases. Development of ligands directly and specifically binding to the Salmonella will be crucial for the rapid detection of, and thus for efficient protection from, the virulent bacteria. In this study, we identified a RNA aptamer-based ligand that can specifically recognize Salmonella Typhimurium through SELEX technology. To this end, we isolated and characterized an RNase-resistant RNA aptamer that bound to the OmpC protein of Salmonella Typhimurium with high specificity and affinity (Kd ~ 20 nM). Of note, the selected aptamer was found to specifically bind to Salmonella Typhimurium, but neither to Gram-positive bacteria (Staphylococcus aureus) nor to other Gram-negative bacteria (Escherichia coli O157:H7). This was evinced by aptamer-immobilized ELISA and aptamer-linked precipitation experiments. This Salmonella species-specific aptamer could be useful as a diagnostic ligand against pathogen-caused foodborne sickness.

Utilizing the algicidal activity of aminoclay as a practical treatment for toxic red tides

PubMed Central

Lee, Young-Chul; Jin, EonSeon; Jung, Seung Won; Kim, Yeon-Mi; Chang, Kwang Suk; Yang, Ji-Won; Kim, Si-Wouk; Kim, Young-Ok; Shin, Hyun-Jae

2013-01-01

In recent decades, harmful algal blooms (HABs) – commonly known as red tides – have increasingly impacted human health, caused significant economic losses to fisheries and damaged coastal environments and ecosystems. Here, we demonstrate a method to control and suppress HABs through selective algal lysis. The approach harnesses the algicidal effects of aminoclays, which are comprised of a high density of primary amine groups covalently bonded by metal cation backbones. Positively charged colloidals of aminoclays induce cell lysis in HABs within several minutes exposure but have negligible impact on non-harmful phytoplankton, zooplankton and farmed fish. This selective lysis is due to the ammonium characteristics of the aminoclay and the electrostatic attraction between the clay nanoparticles and the algal cells. In contrast, yellow loess clay, a recognized treatment for HABs, causes algal flocs with little cell lysis. Thus, the aminoclay loading can be effective for the mitigation of HABs. PMID:23416422

Utilizing the algicidal activity of aminoclay as a practical treatment for toxic red tides.

PubMed

Lee, Young-Chul; Jin, EonSeon; Jung, Seung Won; Kim, Yeon-Mi; Chang, Kwang Suk; Yang, Ji-Won; Kim, Si-Wouk; Kim, Young-Ok; Shin, Hyun-Jae

2013-01-01

In recent decades, harmful algal blooms (HABs) - commonly known as red tides - have increasingly impacted human health, caused significant economic losses to fisheries and damaged coastal environments and ecosystems. Here, we demonstrate a method to control and suppress HABs through selective algal lysis. The approach harnesses the algicidal effects of aminoclays, which are comprised of a high density of primary amine groups covalently bonded by metal cation backbones. Positively charged colloidals of aminoclays induce cell lysis in HABs within several minutes exposure but have negligible impact on non-harmful phytoplankton, zooplankton and farmed fish. This selective lysis is due to the ammonium characteristics of the aminoclay and the electrostatic attraction between the clay nanoparticles and the algal cells. In contrast, yellow loess clay, a recognized treatment for HABs, causes algal flocs with little cell lysis. Thus, the aminoclay loading can be effective for the mitigation of HABs.

Human Behavior and Cognition in Evolutionary Economics.

PubMed

Nelson, Richard R

2011-12-01

My brand of evolutionary economics recognizes, highlights, that modern economies are always in the process of changing, never fully at rest, with much of the energy coming from innovation. This perspective obviously draws a lot from Schumpeter. Continuing innovation, and the creative destruction that innovation engenders, is driving the system. There are winners and losers in the process, but generally the changes can be regarded as progress. The processes through which economic activity and performance evolve has a lot in common with evolution in biology. In particular, at any time the economy is marked by considerable variety, there are selection forces winnowing on that variety, but also continuing emergence of new ways of doing things and often economic actors. But there also are important differences from biological evolution. In particular, both innovation and selection are to a considerable degree purposive activities, often undertaken on the basis of relatively strong knowledge.

Protozoacidal Trojan-Horse: use of a ligand-lytic peptide for selective destruction of symbiotic protozoa within termite guts.

PubMed

Sethi, Amit; Delatte, Jennifer; Foil, Lane; Husseneder, Claudia

2014-01-01

For novel biotechnology-based termite control, we developed a cellulose bait containing freeze-dried genetically engineered yeast which expresses a protozoacidal lytic peptide attached to a protozoa-recognizing ligand. The yeast acts as a 'Trojan-Horse' that kills the cellulose-digesting protozoa in the termite gut, which leads to the death of termites, presumably due to inefficient cellulose digestion. The ligand targets the lytic peptide specifically to protozoa, thereby increasing its protozoacidal efficiency while protecting non-target organisms. After ingestion of the bait, the yeast propagates in the termite's gut and is spread throughout the termite colony via social interactions. This novel paratransgenesis-based strategy could be a good supplement for current termite control using fortified biological control agents in addition to chemical insecticides. Moreover, this ligand-lytic peptide system could be used for drug development to selectively target disease-causing protozoa in humans or other vertebrates.

Blocking TRPA1 in Respiratory Disorders: Does It Hold a Promise?

PubMed Central

Mukhopadhyay, Indranil; Kulkarni, Abhay; Khairatkar-Joshi, Neelima

2016-01-01

Transient Receptor Potential Ankyrin 1 (TRPA1) ion channel is expressed abundantly on the C fibers that innervate almost entire respiratory tract starting from oral cavity and oropharynx, conducting airways in the trachea, bronchi, terminal bronchioles, respiratory bronchioles and upto alveolar ducts and alveoli. Functional presence of TRPA1 on non-neuronal cells got recognized recently. TRPA1 plays a well-recognized role of “chemosensor”, detecting presence of exogenous irritants and endogenous pro-inflammatory mediators that are implicated in airway inflammation and sensory symptoms like chronic cough, asthma, chronic obstructive pulmonary disease (COPD), allergic rhinitis and cystic fibrosis. TRPA1 can remain activated chronically due to elevated levels and continued presence of such endogenous ligands and pro-inflammatory mediators. Several selective TRPA1 antagonists have been tested in animal models of respiratory disease and their performance is very promising. Although there is no TRPA1 antagonist in advanced clinical trials or approved on market yet to treat respiratory diseases, however, limited but promising evidences available so far indicate likelihood that targeting TRPA1 may present a new therapy in treatment of respiratory diseases in near future. This review will focus on in vitro, animal and human evidences that strengthen the proposed role of TRPA1 in modulation of specific airway sensory responses and also on preclinical and clinical progress of selected TRPA1 antagonists. PMID:27827953

How do infants and adults process communicative events in real time?

PubMed

Yamashiro, Amy; Vouloumanos, Athena

2018-09-01

Speech allows humans to communicate and to navigate the social world. By 12 months, infants recognize that speech elicits appropriate responses from others. However, it is unclear how infants process dynamic communicative scenes and how their processing abilities compare with those of adults. Do infants, like adults, process communicative events while the event is occurring or only after being presented with the outcome? We examined 12-month-olds' and adults' eye movements as they watched a Communicator grasp one (target) of two objects. During the test event, the Communicator could no longer reach the objects, so she spoke or coughed to a Listener, who selected either object. Infants' and adults' patterns of looking to the actors and objects revealed that both groups immediately evaluated the Communicator's speech, but not her cough, as communicative and recognized that the Listener should select the target object only when the Communicator spoke. Furthermore, infants and adults shifted their attention between the actors and the objects in very similar ways. This suggests that 12-month-olds can quickly process communicative events as they occur with adult-like accuracy. However, differences in looking reveal that 12-month-olds process slower than adults. This early developing processing ability may allow infants to learn language and acquire knowledge from communicative interactions. Copyright © 2018 Elsevier Inc. All rights reserved.

Recognizing Materials using Perceptually Inspired Features

PubMed Central

Sharan, Lavanya; Liu, Ce; Rosenholtz, Ruth; Adelson, Edward H.

2013-01-01

Our world consists not only of objects and scenes but also of materials of various kinds. Being able to recognize the materials that surround us (e.g., plastic, glass, concrete) is important for humans as well as for computer vision systems. Unfortunately, materials have received little attention in the visual recognition literature, and very few computer vision systems have been designed specifically to recognize materials. In this paper, we present a system for recognizing material categories from single images. We propose a set of low and mid-level image features that are based on studies of human material recognition, and we combine these features using an SVM classifier. Our system outperforms a state-of-the-art system [Varma and Zisserman, 2009] on a challenging database of real-world material categories [Sharan et al., 2009]. When the performance of our system is compared directly to that of human observers, humans outperform our system quite easily. However, when we account for the local nature of our image features and the surface properties they measure (e.g., color, texture, local shape), our system rivals human performance. We suggest that future progress in material recognition will come from: (1) a deeper understanding of the role of non-local surface properties (e.g., extended highlights, object identity); and (2) efforts to model such non-local surface properties in images. PMID:23914070

Shared resource control between human and computer

NASA Technical Reports Server (NTRS)

Hendler, James; Wilson, Reid

1989-01-01

The advantages of an AI system of actively monitoring human control of a shared resource (such as a telerobotic manipulator) are presented. A system is described in which a simple AI planning program gains efficiency by monitoring human actions and recognizing when the actions cause a change in the system's assumed state of the world. This enables the planner to recognize when an interaction occurs between human actions and system goals, and allows maintenance of an up-to-date knowledge of the state of the world and thus informs the operator when human action would undo a goal achieved by the system, when an action would render a system goal unachievable, and efficiently replans the establishment of goals after human intervention.

Dengue virus infection induces broadly cross-reactive human IgM antibodies that recognize intact virions in humanized BLT-NSG mice.

PubMed

Jaiswal, Smita; Smith, Kenneth; Ramirez, Alejandro; Woda, Marcia; Pazoles, Pamela; Shultz, Leonard D; Greiner, Dale L; Brehm, Michael A; Mathew, Anuja

2015-01-01

The development of small animal models that elicit human immune responses to dengue virus (DENV) is important since prior immunity is a major risk factor for developing severe dengue disease. This study evaluated anti-DENV human antibody (hAb) responses generated from immortalized B cells after DENV-2 infection in NOD-scid IL2rγ(null) mice that were co-transplanted with human fetal thymus and liver tissues (BLT-NSG mice). DENV-specific human antibodies predominantly of the IgM isotype were isolated during acute infection and in convalescence. We found that while a few hAbs recognized the envelope protein produced as a soluble recombinant, a number of hAbs only recognized epitopes on intact virions. The majority of the hAbs isolated during acute infection and in immune mice were serotype-cross-reactive and poorly neutralizing. Viral titers in immune BLT-NSG mice were significantly decreased after challenge with a clinical strain of dengue. DENV-specific hAbs generated in BLT-NSG mice share some of the characteristics of Abs isolated in humans with natural infection. Humanized BLT-NSG mice provide an attractive preclinical platform to assess the immunogenicity of candidate dengue vaccines. © 2014 by the Society for Experimental Biology and Medicine.

Dengue virus infection induces broadly cross-reactive human IgM antibodies that recognize intact virions in humanized BLT-NSG mice

PubMed Central

Jaiswal, Smita; Smith, Kenneth; Ramirez, Alejandro; Woda, Marcia; Pazoles, Pamela; Shultz, Leonard D; Greiner, Dale L; Brehm, Michael A

2015-01-01

The development of small animal models that elicit human immune responses to dengue virus (DENV) is important since prior immunity is a major risk factor for developing severe dengue disease. This study evaluated anti-DENV human antibody (hAb) responses generated from immortalized B cells after DENV-2 infection in NOD-scid IL2rγnull mice that were co-transplanted with human fetal thymus and liver tissues (BLT-NSG mice). DENV-specific human antibodies predominantly of the IgM isotype were isolated during acute infection and in convalescence. We found that while a few hAbs recognized the envelope protein produced as a soluble recombinant, a number of hAbs only recognized epitopes on intact virions. The majority of the hAbs isolated during acute infection and in immune mice were serotype-cross-reactive and poorly neutralizing. Viral titers in immune BLT-NSG mice were significantly decreased after challenge with a clinical strain of dengue. DENV-specific hAbs generated in BLT-NSG mice share some of the characteristics of Abs isolated in humans with natural infection. Humanized BLT-NSG mice provide an attractive preclinical platform to assess the immunogenicity of candidate dengue vaccines. PMID:25125497

Stanford/NASA-Ames Center of Excellence in model-based human performance

NASA Technical Reports Server (NTRS)

Wandell, Brian A.

1990-01-01

The human operator plays a critical role in many aeronautic and astronautic missions. The Stanford/NASA-Ames Center of Excellence in Model-Based Human Performance (COE) was initiated in 1985 to further our understanding of the performance capabilities and performance limits of the human component of aeronautic and astronautic projects. Support from the COE is devoted to those areas of experimental and theoretical work designed to summarize and explain human performance by developing computable performance models. The ultimate goal is to make these computable models available to other scientists for use in design and evaluation of aeronautic and astronautic instrumentation. Within vision science, two topics have received particular attention. First, researchers did extensive work analyzing the human ability to recognize object color relatively independent of the spectral power distribution of the ambient lighting (color constancy). The COE has supported a number of research papers in this area, as well as the development of a substantial data base of surface reflectance functions, ambient illumination functions, and an associated software package for rendering and analyzing image data with respect to these spectral functions. Second, the COE supported new empirical studies on the problem of selecting colors for visual display equipment to enhance human performance in discrimination and recognition tasks.

Chimpanzee-Human Monoclonal Antibodies for Treatment of Chronic Poliovirus Excretors and Emergency Postexposure Prophylaxis▿‡

PubMed Central

Chen, Zhaochun; Chumakov, Konstantin; Dragunsky, Eugenia; Kouiavskaia, Diana; Makiya, Michelle; Neverov, Alexander; Rezapkin, Gennady; Sebrell, Andrew; Purcell, Robert

2011-01-01

Six poliovirus-neutralizing Fabs were recovered from a combinatorial Fab phage display library constructed from bone marrow-derived lymphocytes of immunized chimpanzees. The chimeric chimpanzee-human full-length IgGs (hereinafter called monoclonal antibodies [MAbs]) were generated by combining a chimpanzee IgG light chain and a variable domain of heavy chain with a human constant Fc region. The six MAbs neutralized vaccine strains and virulent strains of poliovirus. Five MAbs were serotype specific, while one MAb cross-neutralized serotypes 1 and 2. Epitope mapping performed by selecting and sequencing antibody-resistant viral variants indicated that the cross-neutralizing MAb bound between antigenic sites 1 and 2, thereby covering the canyon region containing the receptor-binding site. Another serotype 1-specific MAb recognized a region located between antigenic sites 2 and 3 that included parts of capsid proteins VP1 and VP3. Both serotype 2-specific antibodies recognized antigenic site 1. No escape mutants to serotype 3-specific MAbs could be generated. The administration of a serotype 1-specific MAb to transgenic mice susceptible to poliovirus at a dose of 5 μg/mouse completely protected them from paralysis after challenge with a lethal dose of wild-type poliovirus. Moreover, MAb injection 6 or 12 h after virus infection provided significant protection. The MAbs described here could be tested in clinical trials to determine whether they might be useful for treatment of immunocompromised chronic virus excretors and for emergency protection of contacts of a paralytic poliomyelitis case. PMID:21345966

Adaptation of human skin color in various populations.

PubMed

Deng, Lian; Xu, Shuhua

2018-01-01

Skin color is a well-recognized adaptive trait and has been studied extensively in humans. Understanding the genetic basis of adaptation of skin color in various populations has many implications in human evolution and medicine. Impressive progress has been made recently to identify genes associated with skin color variation in a wide range of geographical and temporal populations. In this review, we discuss what is currently known about the genetics of skin color variation. We enumerated several cases of skin color adaptation in global modern humans and archaic hominins, and illustrated why, when, and how skin color adaptation occurred in different populations. Finally, we provided a summary of the candidate loci associated with pigmentation, which could be a valuable reference for further evolutionary and medical studies. Previous studies generally indicated a complex genetic mechanism underlying the skin color variation, expanding our understanding of the role of population demographic history and natural selection in shaping genetic and phenotypic diversity in humans. Future work is needed to dissect the genetic architecture of skin color adaptation in numerous ethnic minority groups around the world, which remains relatively obscure compared with that of major continental groups, and to unravel the exact genetic basis of skin color adaptation.

Speech Emotion Feature Selection Method Based on Contribution Analysis Algorithm of Neural Network

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

Wang Xiaojia; Mao Qirong; Zhan Yongzhao

There are many emotion features. If all these features are employed to recognize emotions, redundant features may be existed. Furthermore, recognition result is unsatisfying and the cost of feature extraction is high. In this paper, a method to select speech emotion features based on contribution analysis algorithm of NN is presented. The emotion features are selected by using contribution analysis algorithm of NN from the 95 extracted features. Cluster analysis is applied to analyze the effectiveness for the features selected, and the time of feature extraction is evaluated. Finally, 24 emotion features selected are used to recognize six speech emotions.more » The experiments show that this method can improve the recognition rate and the time of feature extraction.« less

An active learning approach for rapid characterization of endothelial cells in human tumors.

PubMed

Padmanabhan, Raghav K; Somasundar, Vinay H; Griffith, Sandra D; Zhu, Jianliang; Samoyedny, Drew; Tan, Kay See; Hu, Jiahao; Liao, Xuejun; Carin, Lawrence; Yoon, Sam S; Flaherty, Keith T; Dipaola, Robert S; Heitjan, Daniel F; Lal, Priti; Feldman, Michael D; Roysam, Badrinath; Lee, William M F

2014-01-01

Currently, no available pathological or molecular measures of tumor angiogenesis predict response to antiangiogenic therapies used in clinical practice. Recognizing that tumor endothelial cells (EC) and EC activation and survival signaling are the direct targets of these therapies, we sought to develop an automated platform for quantifying activity of critical signaling pathways and other biological events in EC of patient tumors by histopathology. Computer image analysis of EC in highly heterogeneous human tumors by a statistical classifier trained using examples selected by human experts performed poorly due to subjectivity and selection bias. We hypothesized that the analysis can be optimized by a more active process to aid experts in identifying informative training examples. To test this hypothesis, we incorporated a novel active learning (AL) algorithm into FARSIGHT image analysis software that aids the expert by seeking out informative examples for the operator to label. The resulting FARSIGHT-AL system identified EC with specificity and sensitivity consistently greater than 0.9 and outperformed traditional supervised classification algorithms. The system modeled individual operator preferences and generated reproducible results. Using the results of EC classification, we also quantified proliferation (Ki67) and activity in important signal transduction pathways (MAP kinase, STAT3) in immunostained human clear cell renal cell carcinoma and other tumors. FARSIGHT-AL enables characterization of EC in conventionally preserved human tumors in a more automated process suitable for testing and validating in clinical trials. The results of our study support a unique opportunity for quantifying angiogenesis in a manner that can now be tested for its ability to identify novel predictive and response biomarkers.

The importance of physical strength to human males.

PubMed

Sell, Aaron; Hone, Liana S E; Pound, Nicholas

2012-03-01

Fighting ability, although recognized as fundamental to intrasexual competition in many nonhuman species, has received little attention as an explanatory variable in the social sciences. Multiple lines of evidence from archaeology, criminology, anthropology, physiology, and psychology suggest that fighting ability was a crucial aspect of intrasexual competition for ancestral human males, and this has contributed to the evolution of numerous physical and psychological sex differences. Because fighting ability was relevant to many domains of interaction, male psychology should have evolved such that a man's attitudes and behavioral responses are calibrated according to his formidability. Data are reviewed showing that better fighters feel entitled to better outcomes, set lower thresholds for anger/aggression, have self-favoring political attitudes, and believe more in the utility of warfare. New data are presented showing that among Hollywood actors, those selected for their physical strength (i.e., action stars) are more likely to believe in the utility of warfare.

In vitro susceptibility of Scedosporium isolates to N-acetyl-L-cysteine alone and in combination with conventional antifungal agents.

PubMed

Homa, Mónika; Galgóczy, László; Tóth, Eszter; Virágh, Máté; Chandrasekaran, Muthusamy; Vágvölgyi, Csaba; Papp, Tamás

2016-10-01

In recent years, Scedosporium species have been more commonly recognized from severe, difficult-to-treat human infections, such as upper respiratory tract and pulmonary infections. To select an appropriate therapeutic approach for these infections is challenging, because of the commonly observed resistance of the causative agents to several antifungal drugs. Therefore, to find a novel strategy for the treatment of pulmonary Scedosporium infections the in vitro antifungal effect of a mucolytic agent, N-acetyl-L-cysteine and its in vitro combinations with conventional antifungals were investigated. Synergistic and indifferent interactions were registered in 23 and 13 cases, respectively. Antagonism was not revealed between the compounds. © The Author 2016. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Mechanisms of attention

PubMed Central

Lu, Zhong-Lin

2009-01-01

Sensory physiologists and psychologists have recognized the importance of attention on human performance for more than 100 years. Since the 1970s, controlled and extensive experiments have examined effects of selective attention to a location in space or to an object. In addition to behavioral studies, cognitive neuroscientists have investigated the neural bases of attention. In this paper, I briefly review some classical attention paradigms, recent advances on the theory of attention, and some new insights from psychophysics and cognitive neuroscience. The focus is on the mechanisms of attention, that is, how attention improves human performance. Situations in which the perception of objects is unchanged, but performance may differ due to different decision structures, are distinguished from those in which attention changes the perceptual processes. The perceptual template model is introduced as a theoretical framework for analyzing mechanisms of attention. I also present empirical evidence for two attention mechanisms, stimulus enhancement and external noise exclusion, from psychophysics, neurophysiology and brain imaging. PMID:20523762

Highly sensitive chemiluminescent point mutation detection by circular strand-displacement amplification reaction.

PubMed

Shi, Chao; Ge, Yujie; Gu, Hongxi; Ma, Cuiping

2011-08-15

Single nucleotide polymorphism (SNP) genotyping is attracting extensive attentions owing to its direct connections with human diseases including cancers. Here, we have developed a highly sensitive chemiluminescence biosensor based on circular strand-displacement amplification and the separation by magnetic beads reducing the background signal for point mutation detection at room temperature. This method took advantage of both the T4 DNA ligase recognizing single-base mismatch with high selectivity and the strand-displacement reaction of polymerase to perform signal amplification. The detection limit of this method was 1.3 × 10(-16)M, which showed better sensitivity than that of most of those reported detection methods of SNP. Additionally, the magnetic beads as carrier of immobility was not only to reduce the background signal, but also may have potential apply in high through-put screening of SNP detection in human genome. Copyright © 2011 Elsevier B.V. All rights reserved.

The birth of tragedy in pediatrics: a phronetic conception of bioethics.

PubMed

Carnevale, Franco A

2007-09-01

Accepted standards of parental decisional autonomy and child best interests do not address adequately the complex moral problems involved in the care of critically ill children. A growing body of moral discourse is calling for the recognition of ;tragedy' in selected human problems. A tragic dilemma is an irresolvable dilemma with forced terrible alternatives, where even the virtuous agent inescapably emerges with ;dirty hands'. The shift in moral framework described here recognizes that the form of conduct called for by tragic dilemmas is the practice of phronesis. The phronetic agent has acquired a capacity to discern good agency in tragic circumstances. This discernment is practiced through the artful creation of moral narratives: stories that convey that which is morally meaningful in a particular situation; that is, stories that are ;meaning making'. The phronetic agent addresses tragic dilemmas involving children as a narrator of contextualized temporal embodied human (counter)stories.

Mineral Element Contents in Commercially Valuable Fish Species in Spain

PubMed Central

Peña-Rivas, Luis; Ortega, Eduardo; López-Martínez, Concepción; Olea-Serrano, Fátima; Lorenzo, Maria Luisa

2014-01-01

The aim of this study was to measure selected metal concentrations in Trachurus trachurus, Trachurus picturatus, and Trachurus mediterraneus, which are widely consumed in Spain. Principal component analysis suggested that the variable Cr was the main responsible variable for the identification of T. trachurus, the variables As and Sn for T. mediterraneus, and the rest of variables for T. picturatus. This well-defined discrimination between fish species provided by mineral element allows us to distinguish them on the basis of their metal content. Based on the samples collected, and recognizing the inferential limitation of the sample size of this study, the metal concentrations found are below the proposed limit values for human consumption. However, it should be taken into consideration that there are other dietary sources of these metals. In conclusion, metal contents in the fish species analyzed are acceptable for human consumption from a nutritional and toxicity point of view. PMID:24895678

The Impact of the Milk Glycobiome on the Neonate Gut Microbiota

PubMed Central

Pacheco, Alline R.; Barile, Daniela; Underwood, Mark A.; Mills, David A.

2015-01-01

Human milk is a complete source of nourishment for the infant. Exclusive breastfeeding not only sustains the infant’s development but also guides the proliferation of a protective intestinal microbiota. Among the many components of milk that modulate the infant gut microbiota, the milk glycans, which comprise free oligosaccharides, glycoproteins, and glycolipids, are increasingly recognized as drivers of microbiota development and overall gut health. These glycans may display pleiotropic functions, conferring protection against infectious diseases and also acting as prebiotics, selecting for the growth of beneficial intestinal bacteria. The prebiotic effect of milk glycans has direct application to prevention of diseases such as necrotizing enterocolitis, a common and devastating disease of preterm infants. In this article, we review the impact of the human (and bovine) milk glycome on gut health through establishment of a milk-oriented microbiota in the neonate. PMID:25387230

Oral antibodies to human intestinal alkaline phosphatase reduce dietary phytate phosphate bioavailability in the presence of dietary 1α-hydroxycholecalciferol.

PubMed

Bobeck, Elizabeth A; Hellestad, Erica M; Helvig, Christian F; Petkovich, P Martin; Cook, Mark E

2016-03-01

While it is well established that active vitamin D treatment increases dietary phytate phosphate utilization, the mechanism by which intestinal alkaline phosphatase (IAP) participates in phytate phosphate use is less clear. The ability of human IAP (hIAP) oral antibodies to prevent dietary phytate phosphate utilization in the presence of 1α-hydroxycholecalciferol (1α-(OH) D3) in a chick model was investigated. hIAP specific chicken immunoglobulin Y (IgY) antibodies were generated by inoculating laying hens with 17 synthetic peptides derived from the human IAP amino acid sequence and harvesting egg yolk. Western blot analysis showed all antibodies recognized hIAP and 6 of the 8 antibodies selected showed modest inhibition of hIAP activity in vitro (6 to 33% inhibition). In chicks where dietary phosphate was primarily in the form of phytate, 4 selected hIAP antibodies inhibited 1α-(OH) D3-induced increases in blood phosphate, one of which, generated against selected peptide (MFPMGTPD), was as effective as sevelamer hydrochloride in preventing the 1α-(OH) D3-induced increase in blood phosphate, but ineffective in preventing an increase in body weight gain and bone ash induced by 1α-(OH) D3. These studies demonstrated that orally-delivered antibodies to IAP limit dietary phytate-phosphate utilization in chicks treated with 1α-(OH) D3, and implicate IAP as an important host enzyme in increasing phytate phosphate bioavailability in 1α-(OH) D3 fed chicks. © 2015 Poultry Science Association Inc.

Functionalization of Tactile Sensation for Robot Based on Haptograph and Modal Decomposition

NASA Astrophysics Data System (ADS)

Yokokura, Yuki; Katsura, Seiichiro; Ohishi, Kiyoshi

In the real world, robots should be able to recognize the environment in order to be of help to humans. A video camera and a laser range finder are devices that can help robots recognize the environment. However, these devices cannot obtain tactile information from environments. Future human-assisting-robots should have the ability to recognize haptic signals, and a disturbance observer can possibly be used to provide the robot with this ability. In this study, a disturbance observer is employed in a mobile robot to functionalize the tactile sensation. This paper proposes a method that involves the use of haptograph and modal decomposition for the haptic recognition of road environments. The haptograph presents a graphic view of the tactile information. It is possible to classify road conditions intuitively. The robot controller is designed by considering the decoupled modal coordinate system, which consists of translational and rotational modes. Modal decomposition is performed by using a quarry matrix. Once the robot is provided with the ability to recognize tactile sensations, its usefulness to humans will increase.

Selective attention reduces physiological noise in the external ear canals of humans. II: Visual attention

PubMed Central

Walsh, Kyle P.; Pasanen, Edward G.; McFadden, Dennis

2014-01-01

Human subjects performed in several behavioral conditions requiring, or not requiring, selective attention to visual stimuli. Specifically, the attentional task was to recognize strings of digits that had been presented visually. A nonlinear version of the stimulus-frequency otoacoustic emission (SFOAE), called the nSFOAE, was collected during the visual presentation of the digits. The segment of the physiological response discussed here occurred during brief silent periods immediately following the SFOAE-evoking stimuli. For all subjects tested, the physiological-noise magnitudes were substantially weaker (less noisy) during the tasks requiring the most visual attention. Effect sizes for the differences were >2.0. Our interpretation is that cortico-olivo influences adjusted the magnitude of efferent activation during the SFOAE-evoking stimulation depending upon the attention task in effect, and then that magnitude of efferent activation persisted throughout the silent period where it also modulated the physiological noise present. Because the results were highly similar to those obtained when the behavioral conditions involved auditory attention, similar mechanisms appear to operate both across modalities and within modalities. Supplementary measurements revealed that the efferent activation was spectrally global, as it was for auditory attention. PMID:24732070

Switching on fluorescence for selective visual recognition of naringenin and morin with a metal-organic coordination polymer of Zn(bix) [bix = 1,4-bis(imidazol-1-ylmethyl)benzene

NASA Astrophysics Data System (ADS)

Zhao, Xi Juan; Wang, Hui Juan; Liang, Li Jiao; Li, Yuan Fang

2013-02-01

Flavonoids such as naringenin and morin are ubiquitous in a wide range of foods isolated from plants, and have diverse effects on plants even on human health. Here, we establish a selective visual method for recognition of aringenin and morin based on the "switched on" fluorescence induced by a metal-organic coordination polymer of Zn(bix) [bix = 1,4-bis(imidazol-1-ylmethyl)benzene]. Owing to the coordination interaction of aringenin and morin with Zn(II) from the polymeric structure of Zn(bix), the conformational free rotation of naringenin and morin is restricted leading to relatively rigid structures. And as a consequence, the fluorescence is switched on. While luteolin and quercetin, holding a very similar structure with naringenin and morin, have no such fluorescence enhancement most likely owing to the 3'-hydroxy substitution in the B ring. Under 365 nm UV lamp light, we can visually recognize and discriminate naringenin and morin from them each other and luteolin as well as quercetin based on the colors of their emission. With this recognition system, the detection of naringenin and morin in human urine was made with satisfactory results.

Physiological IgM Class Catalytic Antibodies Selective for Transthyretin Amyloid*

PubMed Central

Planque, Stephanie A.; Nishiyama, Yasuhiro; Hara, Mariko; Sonoda, Sari; Murphy, Sarah K.; Watanabe, Kenji; Mitsuda, Yukie; Brown, Eric L.; Massey, Richard J.; Primmer, Stanley R.; O'Nuallain, Brian; Paul, Sudhir

2014-01-01

Peptide bond-hydrolyzing catalytic antibodies (catabodies) could degrade toxic proteins, but acquired immunity principles have not provided evidence for beneficial catabodies. Transthyretin (TTR) forms misfolded β-sheet aggregates responsible for age-associated amyloidosis. We describe nucleophilic catabodies from healthy humans without amyloidosis that degraded misfolded TTR (misTTR) without reactivity to the physiological tetrameric TTR (phyTTR). IgM class B cell receptors specifically recognized the electrophilic analog of misTTR but not phyTTR. IgM but not IgG class antibodies hydrolyzed the particulate and soluble misTTR species. No misTTR-IgM binding was detected. The IgMs accounted for essentially all of the misTTR hydrolytic activity of unfractionated human serum. The IgMs did not degrade non-amyloidogenic, non-superantigenic proteins. Individual monoclonal IgMs (mIgMs) expressed variable misTTR hydrolytic rates and differing oligoreactivity directed to amyloid β peptide and microbial superantigen proteins. A subset of the mIgMs was monoreactive for misTTR. Excess misTTR was dissolved by a hydrolytic mIgM. The studies reveal a novel antibody property, the innate ability of IgMs to selectively degrade and dissolve toxic misTTR species as a first line immune function. PMID:24648510

Development of a Guide-Dog Robot: Leading and Recognizing a Visually-Handicapped Person using a LRF

NASA Astrophysics Data System (ADS)

Saegusa, Shozo; Yasuda, Yuya; Uratani, Yoshitaka; Tanaka, Eiichirou; Makino, Toshiaki; Chang, Jen-Yuan (James

A conceptual Guide-Dog Robot prototype to lead and to recognize a visually-handicapped person is developed and discussed in this paper. Key design features of the robot include a movable platform, human-machine interface, and capability of avoiding obstacles. A novel algorithm enabling the robot to recognize its follower's locomotion as well to detect the center of corridor is proposed and implemented in the robot's human-machine interface. It is demonstrated that using the proposed novel leading and detecting algorithm along with a rapid scanning laser range finder (LRF) sensor, the robot is able to successfully and effectively lead a human walking in corridor without running into obstacles such as trash boxes or adjacent walking persons. Position and trajectory of the robot leading a human maneuvering in common corridor environment are measured by an independent LRF observer. The measured data suggest that the proposed algorithms are effective to enable the robot to detect center of the corridor and position of its follower correctly.

An efficient method for automatic morphological abnormality detection from human sperm images.

PubMed

Ghasemian, Fatemeh; Mirroshandel, Seyed Abolghasem; Monji-Azad, Sara; Azarnia, Mahnaz; Zahiri, Ziba

2015-12-01

Sperm morphology analysis (SMA) is an important factor in the diagnosis of human male infertility. This study presents an automatic algorithm for sperm morphology analysis (to detect malformation) using images of human sperm cells. The SMA method was used to detect and analyze different parts of the human sperm. First of all, SMA removes the image noises and enhances the contrast of the image to a great extent. Then it recognizes the different parts of sperm (e.g., head, tail) and analyzes the size and shape of each part. Finally, the algorithm classifies each sperm as normal or abnormal. Malformations in the head, midpiece, and tail of a sperm, can be detected by the SMA method. In contrast to other similar methods, the SMA method can work with low resolution and non-stained images. Furthermore, an image collection created for the SMA, has also been described in this study. This benchmark consists of 1457 sperm images from 235 patients, and is known as human sperm morphology analysis dataset (HSMA-DS). The proposed algorithm was tested on HSMA-DS. The experimental results show the high ability of SMA to detect morphological deformities from sperm images. In this study, the SMA algorithm produced above 90% accuracy in sperm abnormality detection task. Another advantage of the proposed method is its low computation time (that is, less than 9s), as such, the expert can quickly decide to choose the analyzed sperm or select another one. Automatic and fast analysis of human sperm morphology can be useful during intracytoplasmic sperm injection for helping embryologists to select the best sperm in real time. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Generation of novel covalent RNA-protein complexes in cells by ultraviolet B irradiation: implications for autoimmunity.

PubMed

Andrade, Felipe; Casciola-Rosen, Livia A; Rosen, Antony

2005-04-01

To determine whether ultraviolet B (UVB) irradiation induces novel modifications in autoantigens targeted during experimental photoinduced epidermal damage. To search for novel UVB-induced autoantigen modifications, lysates made from UVB-irradiated human keratinocytes or HeLa cells were immunoblotted using human autoantibodies that recognize ribonucleoprotein autoantigens. Novel autoantigen structures identified were further characterized using nucleases and RNA hybridization. Human sera that recognize U1-70 kd (U1-70K) and La by immunoblotting also recognized multiple novel species when they were used to immunoblot lysates of UVB-irradiated keratinocytes or HeLa cells. These species were not present in control cells and were not observed when apoptosis was induced by Fas ligation or cytotoxic lymphocyte granule contents. Biochemical analysis using multiple assays revealed that these novel UVB-induced molecular species result from the covalent crosslinking between the U1 RNA and the hYRNA molecules with their associated proteins, including U1-70K, La, and likely components of the Sm particle. These data demonstrate that UVB irradiation of live cells can directly induce covalent RNA-protein complexes, which are recognized by human autoantibodies. As previously described for other autoantigens, these covalent complexes of RNA and proteins may have important consequences in terms of antigen capture and processing.

(−)-Xanthatin Selectively Induces GADD45γ and Stimulates Caspase-Independent Cell Death in Human Breast Cancer MDA-MB-231 Cells

PubMed Central

Takeda, Shuso; Matsuo, Kazumasa; Yaji, Kentaro; Okajima-Miyazaki, Shunsuke; Harada, Mari; Miyoshi, Hiroko; Okamoto, Yoshiko; Amamoto, Toshiaki; Shindo, Mitsuru; Omiecinski, Curtis J.; Aramaki, Hironori

2014-01-01

exo-Methylene lactone group-containing compounds, such as (−)-xanthatin, are present in a large variety of biologically active natural products, including extracts of Xanthium strumarium (Cocklebur). These substances are reported to possess diverse functional activities, exhibiting anti-inflammatory, antimalarial, and anticancer potential. In this study, we synthesized six structurally related xanthanolides containing exo-methylene lactone moieties, including (−)-xanthatin and (+)-8-epi-xanthatin, and examined the effects of these chemically defined substances on the highly aggressive and farnesyltransferase inhibitor (FTI)-resistant MDA-MB-231 cancer cell line. The results obtained demonstrate that (−)-xanthatin was a highly effective inhibitor of MDA-MB-231 cell growth, inducing caspase-independent cell death, and that these effects were independent of FTase inhibition. Further, our results show that among the GADD45 isoforms, GADD45γ was selectively induced by (−)-xanthatin and that GADD45γ-primed JNK and p38 signaling pathways are, at least in part, involved in mediating the growth inhibition and potential anticancer activities of this agent. Given that GADD45γ is becoming increasingly recognized for its tumor suppressor function, the results presented here suggest the novel possibility that (−)-xanthatin may have therapeutic value as a selective inducer of GADD45γ in human cancer cells, in particular in FTI-resistant aggressive breast cancers. PMID:21568272

Feature Selection Method Based on Neighborhood Relationships: Applications in EEG Signal Identification and Chinese Character Recognition

PubMed Central

Zhao, Yu-Xiang; Chou, Chien-Hsing

2016-01-01

In this study, a new feature selection algorithm, the neighborhood-relationship feature selection (NRFS) algorithm, is proposed for identifying rat electroencephalogram signals and recognizing Chinese characters. In these two applications, dependent relationships exist among the feature vectors and their neighboring feature vectors. Therefore, the proposed NRFS algorithm was designed for solving this problem. By applying the NRFS algorithm, unselected feature vectors have a high priority of being added into the feature subset if the neighboring feature vectors have been selected. In addition, selected feature vectors have a high priority of being eliminated if the neighboring feature vectors are not selected. In the experiments conducted in this study, the NRFS algorithm was compared with two feature algorithms. The experimental results indicated that the NRFS algorithm can extract the crucial frequency bands for identifying rat vigilance states and identifying crucial character regions for recognizing Chinese characters. PMID:27314346

Genome-Scale Protein Microarray Comparison of Human Antibody Responses in Plasmodium vivax Relapse and Reinfection

PubMed Central

Chuquiyauri, Raul; Molina, Douglas M.; Moss, Eli L.; Wang, Ruobing; Gardner, Malcolm J.; Brouwer, Kimberly C.; Torres, Sonia; Gilman, Robert H.; Llanos-Cuentas, Alejandro; Neafsey, Daniel E.; Felgner, Philip; Liang, Xiaowu; Vinetz, Joseph M.

2015-01-01

Large scale antibody responses in Plasmodium vivax malaria remains unexplored in the endemic setting. Protein microarray analysis of asexual-stage P. vivax was used to identify antigens recognized in sera from residents of hypoendemic Peruvian Amazon. Over 24 months, of 106 participants, 91 had two symptomatic P. vivax malaria episodes, 11 had three episodes, 3 had four episodes, and 1 had five episodes. Plasmodium vivax relapse was distinguished from reinfection by a merozoite surface protein-3α restriction fragment length polymorphism polymerase chain reaction (MSP3α PCR-RFLP) assay. Notably, P. vivax reinfection subjects did not have higher reactivity to the entire set of recognized P. vivax blood-stage antigens than relapse subjects, regardless of the number of malaria episodes. The most highly recognized P. vivax proteins were MSP 4, 7, 8, and 10 (PVX_003775, PVX_082650, PVX_097625, and PVX_114145); sexual-stage antigen s16 (PVX_000930); early transcribed membrane protein (PVX_090230); tryptophan-rich antigen (Pv-fam-a) (PVX_092995); apical merozoite antigen 1 (PVX_092275); and proteins of unknown function (PVX_081830, PVX_117680, PVX_118705, PVX_121935, PVX_097730, PVX_110935, PVX_115450, and PVX_082475). Genes encoding reactive proteins exhibited a significant enrichment of non-synonymous nucleotide variation, an observation suggesting immune selection. These data identify candidates for seroepidemiological tools to support malaria elimination efforts in P. vivax-endemic regions. PMID:26149860

Recognition and classification of colon cells applying the ensemble of classifiers.

PubMed

Kruk, M; Osowski, S; Koktysz, R

2009-02-01

The paper presents the application of an ensemble of classifiers for the recognition of colon cells on the basis of the microscope colon image. The solved task include: segmentation of the individual cells from the image using the morphological operations, the preprocessing stages, leading to the extraction of features, selection of the most important features, and the classification stage applying the classifiers arranged in the form of ensemble. The paper presents and discusses the results concerning the recognition of four most important colon cell types: eosinophylic granulocyte, neutrophilic granulocyte, lymphocyte and plasmocyte. The proposed system is able to recognize the cells with the accuracy comparable to the human expert (around 5% of discrepancy of both results).

Animal models for microbicide safety and efficacy testing.

PubMed

Veazey, Ronald S

2013-07-01

Early studies have cast doubt on the utility of animal models for predicting success or failure of HIV-prevention strategies, but results of multiple human phase 3 microbicide trials, and interrogations into the discrepancies between human and animal model trials, indicate that animal models were, and are, predictive of safety and efficacy of microbicide candidates. Recent studies have shown that topically applied vaginal gels, and oral prophylaxis using single or combination antiretrovirals are indeed effective in preventing sexual HIV transmission in humans, and all of these successes were predicted in animal models. Further, prior discrepancies between animal and human results are finally being deciphered as inadequacies in study design in the model, or quite often, noncompliance in human trials, the latter being increasingly recognized as a major problem in human microbicide trials. Successful microbicide studies in humans have validated results in animal models, and several ongoing studies are further investigating questions of tissue distribution, duration of efficacy, and continued safety with repeated application of these, and other promising microbicide candidates in both murine and nonhuman primate models. Now that we finally have positive correlations with prevention strategies and protection from HIV transmission, we can retrospectively validate animal models for their ability to predict these results, and more importantly, prospectively use these models to select and advance even safer, more effective, and importantly, more durable microbicide candidates into human trials.

An engineered high affinity Fbs1 carbohydrate binding protein for selective capture of N-glycans and N-glycopeptides

PubMed Central

Chen, Minyong; Shi, Xiaofeng; Duke, Rebecca M.; Ruse, Cristian I.; Dai, Nan; Taron, Christopher H.; Samuelson, James C.

2017-01-01

A method for selective and comprehensive enrichment of N-linked glycopeptides was developed to facilitate detection of micro-heterogeneity of N-glycosylation. The method takes advantage of the inherent properties of Fbs1, which functions within the ubiquitin-mediated degradation system to recognize the common core pentasaccharide motif (Man3GlcNAc2) of N-linked glycoproteins. We show that Fbs1 is able to bind diverse types of N-linked glycomolecules; however, wild-type Fbs1 preferentially binds high-mannose-containing glycans. We identified Fbs1 variants through mutagenesis and plasmid display selection, which possess higher affinity and improved recovery of complex N-glycomolecules. In particular, we demonstrate that the Fbs1 GYR variant may be employed for substantially unbiased enrichment of N-linked glycopeptides from human serum. Most importantly, this highly efficient N-glycopeptide enrichment method enables the simultaneous determination of N-glycan composition and N-glycosites with a deeper coverage (compared to lectin enrichment) and improves large-scale N-glycoproteomics studies due to greatly reduced sample complexity. PMID:28534482

Robotic situational awareness of actions in human teaming

NASA Astrophysics Data System (ADS)

Tahmoush, Dave

2015-06-01

When robots can sense and interpret the activities of the people they are working with, they become more of a team member and less of just a piece of equipment. This has motivated work on recognizing human actions using existing robotic sensors like short-range ladar imagers. These produce three-dimensional point cloud movies which can be analyzed for structure and motion information. We skeletonize the human point cloud and apply a physics-based velocity correlation scheme to the resulting joint motions. The twenty actions are then recognized using a nearest-neighbors classifier that achieves good accuracy.

RecceMan: an interactive recognition assistance for image-based reconnaissance: synergistic effects of human perception and computational methods for object recognition, identification, and infrastructure analysis

NASA Astrophysics Data System (ADS)

El Bekri, Nadia; Angele, Susanne; Ruckhäberle, Martin; Peinsipp-Byma, Elisabeth; Haelke, Bruno

2015-10-01

This paper introduces an interactive recognition assistance system for imaging reconnaissance. This system supports aerial image analysts on missions during two main tasks: Object recognition and infrastructure analysis. Object recognition concentrates on the classification of one single object. Infrastructure analysis deals with the description of the components of an infrastructure and the recognition of the infrastructure type (e.g. military airfield). Based on satellite or aerial images, aerial image analysts are able to extract single object features and thereby recognize different object types. It is one of the most challenging tasks in the imaging reconnaissance. Currently, there are no high potential ATR (automatic target recognition) applications available, as consequence the human observer cannot be replaced entirely. State-of-the-art ATR applications cannot assume in equal measure human perception and interpretation. Why is this still such a critical issue? First, cluttered and noisy images make it difficult to automatically extract, classify and identify object types. Second, due to the changed warfare and the rise of asymmetric threats it is nearly impossible to create an underlying data set containing all features, objects or infrastructure types. Many other reasons like environmental parameters or aspect angles compound the application of ATR supplementary. Due to the lack of suitable ATR procedures, the human factor is still important and so far irreplaceable. In order to use the potential benefits of the human perception and computational methods in a synergistic way, both are unified in an interactive assistance system. RecceMan® (Reconnaissance Manual) offers two different modes for aerial image analysts on missions: the object recognition mode and the infrastructure analysis mode. The aim of the object recognition mode is to recognize a certain object type based on the object features that originated from the image signatures. The infrastructure analysis mode pursues the goal to analyze the function of the infrastructure. The image analyst extracts visually certain target object signatures, assigns them to corresponding object features and is finally able to recognize the object type. The system offers him the possibility to assign the image signatures to features given by sample images. The underlying data set contains a wide range of objects features and object types for different domains like ships or land vehicles. Each domain has its own feature tree developed by aerial image analyst experts. By selecting the corresponding features, the possible solution set of objects is automatically reduced and matches only the objects that contain the selected features. Moreover, we give an outlook of current research in the field of ground target analysis in which we deal with partly automated methods to extract image signatures and assign them to the corresponding features. This research includes methods for automatically determining the orientation of an object and geometric features like width and length of the object. This step enables to reduce automatically the possible object types offered to the image analyst by the interactive recognition assistance system.

Immune recognition of botulinum neurotoxin B: antibody-binding regions on the heavy chain of the toxin.

PubMed

Dolimbek, Behzod Z; Steward, Lance E; Aoki, K Roger; Atassi, M Zouhair

2008-02-01

The purpose of this work was to map the continuous regions recognized by human, horse and mouse anti-botulinum neurotoxin B (BoNT/B) antibodies (Abs). We synthesized a panel of sixty 19-residue peptides (peptide C31 was 24 residues) that overlapped consecutively by 5 residues and together encompassed the entire heavy chain of BoNT/B (H/B, residues 442-1291). Abs from the three host species recognized similar, but not identical, peptides. There were also peptides recognized by two or only by one host species. Where a peptide was recognized by Abs of more than one host species, these Abs were at different levels among the species. Human, horse and mouse Abs bound, although in different amounts, to regions within peptides 736-754, 778-796, 848-866, 932-950, 974-992, 1058-1076 and 1128-1146. Human and horse Abs bound to peptides 890-908 and 1170-1188. Human and mouse Abs recognized peptides 470-488/484-502 overlap, 638-656, 722-740, 862-880, 1030-1048, 1072-1090, 1240-1258 and 1268-1291. We concluded that the antigenic regions localized with the three antisera are quite similar, exhibiting in some cases a small shift to the left or to the right. This is consistent with what is known about protein immune recognition. In the three-dimensional structure, the regions recognized on H/B by anti-BoNT/B Abs occupied surface locations and analysis revealed no correlation between these surface locations and surface electrostatic potential, hydrophilicity, hydrophobicity, or temperature factor. A region that bound mouse Abs overlapped with a recently defined site on BoNT/B that binds to mouse and rat synaptotagmin II, thus providing a molecular explanation for the blocking (protecting) activity of these Abs. The regions thus localized afford candidates for incorporation into a synthetic vaccine design.

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

D'Aiuto, L.; Marzella, R.; Archidiacono, N.

The authors have isolated and characterized two human alphoid DNA clones: p4n1/4 and pZ4.1. Clone p4n1/4 identifies specifically the centromeric region of chromosome 4; pZ4.1 recognizes a subset of alphoid DNA shared by chromosomes 4 and 9. The specificity was determined using fluorescence in situ hybridization experiments on metaphase spreads and Southern blotting analysis of human-hamster somatic cell hybrids. The genomic organization of both subsets was also investigated. Comparative mapping on chimpanzee and gorilla chromosomes was performed. p4n1/4 hybridizes to chimpanzee chromosomes 11 and 13, homologs of human chromosomes 9 and 2q, respectively. On gorilla metaphase spreads, p4n1/4 hybridizes exclusivelymore » to the centromeric region of chromosome 19, partially homologous to human chromosome 17. No hybridization signal was detected on chromosome 3 of both chimpanzee and gorilla, in both species homolog of human chromosome 4. Identical comparative mapping results were obtained using pZ4.1 probe, although the latter recognizes an alphoid subset distinct from the one recognized by p4n1/4. The implications of these results in the evolution of centromeric regions of primate chromosomes are discussed. 33 refs., 4 figs.« less

The Human Right to Leisure in Old Age: Reinforcement of the Rights of an Aging Population.

PubMed

Karev, Iris; Doron, Israel Issi

2017-01-01

The right to leisure is recognized as a human right under the 1948 United Nations Universal Declaration of Human Rights. The actual meaning and material content of this human right is subject to debate. The aim of this study is to examine the extent and the context to which this human right is specifically recognized with regard to older persons. Methodologically, this study textually analyzed 17 different international older persons' human rights documents. The findings reveal that in the majority of these documents there is no reference to the right to leisure. In the remaining documents, the right to leisure is mostly referred to indirectly or in a narrow legal construction. These findings support the notion that despite the growing body of knowledge regarding the importance of meaningful leisure in old age-and its empowering and anti-ageist nature-this knowledge has not transformed into a legal human rights discourse.

A monoclonal antibody, DL10, which recognizes a sugar moiety of MHC class I antigens expressed on NK cells, NK+ T cells, and granulocytes in humans.

PubMed

Shirai, K; Watanabe, H; Weerasinghe, A; Sakai, T; Sekikawa, H; Abo, T

1997-11-01

One mAb, DL10, was established from mice injected with dolphin lymphocytes. In addition to its reactivity against all dolphin lymphocytes, it reacted with some human leukocytes, including NK cells, NK+ T cells, and granulocytes. When its reactivity was examined in various animals, bovine, ovine, and equine leukocytes were DL10+. Murine, rat, and canine leukocytes were DL10-. Although the reactivity of DL10+ was similar to those of CD56 and CD57 antigens in humans, the actual molecules it recognized were different. Thus, all reactivity of DL10 disappeared after treatment of cells with glycopeptidase or after culture of cells with tunicamycin. Furthermore, the immunoprecipitation method revealed that DL10 indirectly recognized the heavy chain (45kD) of MHC class I antigen in humans and animals. Considering data from analysis of the N-terminal amino acid sequence of the DL10 molecule and the HLA typing of reactive cells, DL10 recognized a sugar moiety of some monomorphic MHC antigens and polymorphic MHC antigens such as HLA-B60 and -B61. If the donors are HLA-B60- and -B61 (> 80% in Japan and > 95% in the United States), DL10 would appear to be a very useful agent for the detection of pan-NK+ T cells.

Charles Darwin and Evolution: Illustrating Human Aspects of Science

NASA Astrophysics Data System (ADS)

Kampourakis, Kostas; McComas, William F.

2010-06-01

Recently, the nature of science (NOS) has become recognized as an important element within the K-12 science curriculum. Despite differences in the ultimate lists of recommended aspects, a consensus is emerging on what specific NOS elements should be the focus of science instruction and inform textbook writers and curriculum developers. In this article, we suggest a contextualized, explicit approach addressing one core NOS aspect: the human aspects of science that include the domains of creativity, social influences and subjectivity. To illustrate these ideas, we have focused on Charles Darwin, a scientist whose life, work and thought processes were particularly well recorded at the time and analyzed by scholars in the succeeding years. Historical facts are discussed and linked to core NOS ideas. Creativity is illustrated through the analogies between the struggle for existence in human societies and in nature, between artificial and natural selection, and between the division of labor in human societies and in nature. Social influences are represented by Darwin’s aversion of criticism of various kinds and by his response to the methodological requirements of the science of that time. Finally, subjectivity is discussed through Darwin’s development of a unique but incorrect source for the origin of variations within species.

Programming by early nutrition: an experimental approach.

PubMed

Lucas, A

1998-02-01

That events during critical or sensitive periods of development may "program" long-term or life-time structure or function of the organism is well recognized. Evidence for programming by nutrition is established in animals, in whom brief pre- or postnatal nutritional manipulations may program adult size, metabolism, blood lipids, diabetes, blood pressure, obesity, atherosclerosis, learning, behavior and life span. Human epidemiological data link potential markers of early nutrition (size at birth or in infancy) to cardiovascular disease and its risk factors in adulthood. However, these retrospective data cannot prove nutritional cause or underpin health policies. After 16 y, however, of ethical, randomized intervention studies of early nutrition in humans with long-term follow-up to test experimentally the nutritional programming hypothesis, we find that humans, like other species, have sensitive windows for nutrition in terms of later outcomes; for instance, perinatal diet influences neurodevelopment and bone mineralization into mid-childhood. Possible biological mechanisms for storing throughout life the "memory" of early nutritional experience and its expression in adulthood include adaptive changes in gene expression, preferential clonal selection of adapted cells in programmed tissues and programmed differential proliferation of tissue cell types. Animal and human evidence supporting nutritional programming has major potential biological and medical significance.

Shining Light on Skin Pigmentation: The Darker and the Brighter Side of Effects of UV Radiation†

PubMed Central

Maddodi, Nityanand; Jayanthy, Ashika; Setaluri, Vijayasaradhi

2012-01-01

The term barrier function as applied to human skin often connotes the physical properties of this organ that provide protection from its surrounding environment. This term does not generally include skin pigmentation. However, skin pigmentation, which is the result of melanin produced in melanocytes residing the basal layer of the skin and exported to the keratinocytes in the upper layers, serves equally important protective function. Indeed, changes in skin pigmentation are often the most readily recognized indicators of exposure of skin to damaging agents, especially to natural and artificial radiation in the environment. Several recent studies have shed new light on a) the mechanisms of involved in selective effects of subcomponents of UV radiation on human skin pigmentation and b) the interactive influences between keratinocytes and melanocytes, acting as ‘epidermal melanin unit’, that manifest as changes in skin pigmentation in response to exposure to various forms of radiation. This article provides a concise review of our current understanding of the effects of the non-ionizing solar radiation, at cellular and molecular levels, on human skin pigmentation. PMID:22404235

Structural basis of O-GlcNAc recognition by mammalian 14-3-3 proteins.

PubMed

Toleman, Clifford A; Schumacher, Maria A; Yu, Seok-Ho; Zeng, Wenjie; Cox, Nathan J; Smith, Timothy J; Soderblom, Erik J; Wands, Amberlyn M; Kohler, Jennifer J; Boyce, Michael

2018-06-05

O-GlcNAc is an intracellular posttranslational modification that governs myriad cell biological processes and is dysregulated in human diseases. Despite this broad pathophysiological significance, the biochemical effects of most O-GlcNAcylation events remain uncharacterized. One prevalent hypothesis is that O-GlcNAc moieties may be recognized by "reader" proteins to effect downstream signaling. However, no general O-GlcNAc readers have been identified, leaving a considerable gap in the field. To elucidate O-GlcNAc signaling mechanisms, we devised a biochemical screen for candidate O-GlcNAc reader proteins. We identified several human proteins, including 14-3-3 isoforms, that bind O-GlcNAc directly and selectively. We demonstrate that 14-3-3 proteins bind O-GlcNAc moieties in human cells, and we present the structures of 14-3-3β/α and γ bound to glycopeptides, providing biophysical insights into O-GlcNAc-mediated protein-protein interactions. Because 14-3-3 proteins also bind to phospho-serine and phospho-threonine, they may integrate information from O-GlcNAc and O-phosphate signaling pathways to regulate numerous physiological functions.

Odor from a chemical perspective

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

Wray, T.K.

1995-06-01

Early odor-detection measurements categorized chemicals according to odor quality. Recent methods focus on the odor threshold, or the quantitative amount of a chemical in air that can be detected by the human sense of smell. Researchers characterize and quantify odor using an array of sensory and analytical procedures. Humans possess one of the dullest mammalian senses of smell; however, they can recognize about 10,000 distinct odors at concentrations ranging from less than 1 part per billion to several hundred thousand parts per million. Each time humans inhale, they chemically analyze microscopic pieces of the environment that make physical contact withmore » the nerves in their noses. Individual molecules travel up the nose to a sheet of moist, mucus-bathed tissue that consists of about 5 million smell-sensing, olfactory neurons. After dissolving in the mucus, odor molecules ``float`` into appropriately shaped receptor pockets. A series of cellular reactions then transmit impulses to the limbic system, hippocampus and, finally, the neocortex. Odor detection is an important defense mechanism. The author presents the odor thresholds for selected organic compounds, and other hazardous chemicals.« less

Phylogenetic and phylodynamic analyses of human metapneumovirus in Buenos Aires (Argentina) for a three-year period (2009-2011).

PubMed

Velez Rueda, Ana Julia; Mistchenko, Alicia Susana; Viegas, Mariana

2013-01-01

Human metapneumovirus, which belongs to the Paramyxoviridae family and has been classified as a member of the Pneumovirus genus, is genetically and clinically similar to other family members such as human respiratory syncytial virus. A total of 1146 nasopharyngeal aspirates from pediatric patients with moderate and severe acute lower respiratory tract infections, hospitalized at the Ricardo Gutierrez Childreńs Hospital (Buenos Aires, Argentina), were tested by real time RT-PCR for human metapneumovirus. Results showed that 168 (14.65%) were positive. Thirty-six of these 168 samples were randomly selected to characterize positive cases molecularly. The phylogenetic analysis of the sequences of the G and F genes showed that genotypes A2 and B2 cocirculated during 2009 and 2010 and that only genotype A2 circulated in 2011 in Argentina. Genotype A2 prevailed during the study period, a fact supported by a higher effective population size (Neτ) and higher diversity as compared to that of genotype B2 (10.9% (SE 1.3%) vs. 1.7% (SE 0.4%), respectively). The phylogeographic analysis of the G protein gene sequences showed that this virus has no geographical restrictions and can travel globally harbored in hosts. The selection pressure analysis of the F protein showed that although this protein has regions with polymorphisms, it has vast structural and functional constraints. In addition, the predicted B-linear epitopes and the sites recognized by previously described monoclonal antibodies were conserved in all Argentine sequences. This points out this protein as a potential candidate to be the target of future humanized antibodies or vaccines.

Molecular Mechanism of MART-1+/A*0201+ Human Melanoma Resistance to Specific CTL-Killing Despite Functional Tumor-CTL Interaction

PubMed Central

Jazirehi, Ali R.; Baritaki, Stavroula; Koya, Richard C.; Bonavida, Benjamin; Economou, James S.

2014-01-01

Durable responses in metastatic melanoma patients remain generally difficult to achieve. Adoptive cell therapy with ex vivo engineered lymphocytes expressing high affinity T cell receptors TCRα/β for the melanoma antigen MART-127-35/HLA A*0201 (recognized by F5 cytotoxic T lymphocytes [F5 CTLs]) has been found to benefit certain patients. However, many other patients are inherently unresponsive and/or relapse for unknown reasons. To analyze the basis for the acquired-resistance and strategies to reverse it, we established F5 CTLresistant (R) human melanoma clones from relatively sensitive parental lines under selective F5 CTL pressure. Surface MART-127-35/HLA-A*0201 in these clones was unaltered and F5 CTLs recognized and interacted with them similarly to the parental lines. Nevertheless, the R clones were resistant to F5 CTL killing, exhibited hyperactivation of the NF-κB survival pathway, and overexpression of the anti-apoptotic genes Bcl-2, Bcl-xL and Mcl-1. Sensitivity to F5 CTL-killing could be increased by pharmacological inhibition of the NF-κB pathway, Bcl-2 family members, or the proteasome, the latter of which reduced NF-κB activity and diminished anti-apoptotic gene expression. Specific gene-silencing (by siRNA) confirmed the protective role of anti-apoptotic factors by reversing R clone resistance. Together, our findings suggest that long-term immunotherapy may impose a selection for the development of resistant cells that are unresponsive to highly avid and specific melanoma-reactive CTLs, despite maintaining expression of functional peptide:MHC complexes, due to activation of anti-apoptotic signaling pathways. Though unresponsive to CTL, our results argue that resistant cells can be re-sensitized to immunotherapy with co-administration of targeted inhibitors to anti-apoptotic survival pathways. PMID:21159666

Oxygen toxicity.

PubMed

Stogner, S W; Payne, D K

1992-12-01

The objective of this article is to provide an overview of the biochemistry of oxygen metabolism, including the formation of free radicals and the role of endogenous antioxidants. Pathophysiologic correlates underlying the clinical manifestations of oxygen toxicity are reviewed and management strategies are outlined. References from basic science and clinical journals were selected from the authors' files and from a search of a computerized database of the biomedical literature. Articles selected for review included both historical and current literature concerning the biochemistry and pathophysiology of oxygen toxicity in animals and humans. The benefits of oxygen therapy have been known for many years; however, its potential toxicity has not been recognized until the last two decades. The lungs, the eyes, and, under certain conditions, the central nervous system are the organs most affected by prolonged exposure to hyperoxic environments. Free radical formation during cellular metabolism under hyperoxic conditions is recognized as the biochemical basis of oxygen injury to cells and organs. Endogenous antioxidants are a primary means of detoxifying reactive oxygen species and preventing hyperoxia-induced cellular damage. When this defense fails or is overwhelmed by the excessive production of hyperoxia-induced free-radical species, distinctive morphologic changes occur at the cellular level. The amount of hyperoxia required to cause cellular damage and the time course of these changes vary from species to species and from individual to individual within the same species. Age, nutritional status, presence of underlying diseases, and certain drugs may influence the development of oxygen toxicity. There is currently no reliably effective drug for preventing or delaying the development of oxygen toxicity in humans. Use of the lowest effective oxygen concentration, the avoidance of certain drugs, and attention to nutritional and metabolic factors remain the best means currently available to avoid or minimize oxygen toxicity. Research is continuing into more effective ways to prevent, diagnose, and treat this disorder.

The Digestive Tract and Derived Primordia Differentiate by Following a Precise Timeline in Human Embryos Between Carnegie Stages 11 and 13.

PubMed

Ueno, Saki; Yamada, Shigehito; Uwabe, Chigako; Männer, Jörg; Shiraki, Naoto; Takakuwa, Tetsuya

2016-04-01

The precise mechanisms through which the digestive tract develops during the somite stage remain undefined. In this study, we examined the morphology and precise timeline of differentiation of digestive tract-derived primordia in human somite-stage embryos. We selected 37 human embryos at Carnegie Stage (CS) 11-CS13 (28-33 days after fertilization) and three-dimensionally analyzed the morphology and positioning of the digestive tract and derived primordia in all samples, using images reconstructed from histological serial sections. The digestive tract was initially formed by a narrowing of the yolk sac, and then several derived primordia such as the pharynx, lung, stomach, liver, and dorsal pancreas primordia differentiated during CS12 (21-29 somites) and CS13 (≥ 30 somites). The differentiation of four pairs of pharyngeal pouches was complete in all CS13 embryos. The respiratory primordium was recognized in ≥ 26-somite embryos and it flattened and then branched at CS13. The trachea formed and then elongated in ≥ 35-somite embryos. The stomach adopted a spindle shape in all ≥ 34-somite embryos, and the liver bud was recognized in ≥ 27-somite embryos. The dorsal pancreas appeared as definitive buddings in all but three CS13 embryos, and around these buddings, the small intestine bent in ≥ 33-somite embryos. In ≥ 35-somite embryos, the small intestine rotated around the cranial-caudal axis and had begun to form a primitive intestinal loop, which led to umbilical herniation. These data indicate that the digestive tract and derived primordia differentiate by following a precise timeline and exhibit limited individual variations. © 2016 Wiley Periodicals, Inc.

Evaluation of speech recognizers for use in advanced combat helicopter crew station research and development

NASA Technical Reports Server (NTRS)

Simpson, Carol A.

1990-01-01

The U.S. Army Crew Station Research and Development Facility uses vintage 1984 speech recognizers. An evaluation was performed of newer off-the-shelf speech recognition devices to determine whether newer technology performance and capabilities are substantially better than that of the Army's current speech recognizers. The Phonetic Discrimination (PD-100) Test was used to compare recognizer performance in two ambient noise conditions: quiet office and helicopter noise. Test tokens were spoken by males and females and in isolated-word and connected-work mode. Better overall recognition accuracy was obtained from the newer recognizers. Recognizer capabilities needed to support the development of human factors design requirements for speech command systems in advanced combat helicopters are listed.

Selection to outsmart the germs: The evolution of disease recognition and social cognition.

PubMed

Kessler, Sharon E; Bonnell, Tyler R; Byrne, Richard W; Chapman, Colin A

2017-07-01

The emergence of providing care to diseased conspecifics must have been a turning point during the evolution of hominin sociality. On a population level, care may have minimized the costs of socially transmitted diseases at a time of increasing social complexity, although individual care-givers probably incurred increased transmission risks. We propose that care-giving likely originated within kin networks, where the costs may have been balanced by fitness increases obtained through caring for ill kin. We test a novel hypothesis of hominin cognitive evolution in which disease may have selected for the cognitive ability to recognize when a conspecific is infected. Because diseases may produce symptoms that are likely detectable via the perceptual-cognitive pathways integral to social cognition, we suggest that disease recognition and social cognition may have evolved together. Using agent-based modeling, we test 1) under what conditions disease can select for increasing disease recognition and care-giving among kin, 2) whether providing care produces greater selection for cognition than an avoidance strategy, and 3) whether care-giving alters the progression of the disease through the population. The greatest selection was produced by diseases with lower risks to the care-giver and prevalences low enough not to disrupt the kin networks. When care-giving and avoidance strategies were compared, only care-giving reduced the severity of the disease outbreaks and subsequent population crashes. The greatest selection for increased cognitive abilities occurred early in the model runs when the outbreaks and population crashes were most severe. Therefore, over the course of human evolution, repeated introductions of novel diseases into naïve populations could have produced sustained selection for increased disease recognition and care-giving behavior, leading to the evolution of increased cognition, social complexity, and, eventually, medical care in humans. Finally, we lay out predictions derived from our disease recognition hypothesis that we encourage paleoanthropologists, bioarchaeologists, primatologists, and paleogeneticists to test. Copyright © 2017 Elsevier Ltd. All rights reserved.

Nucleic acid constructs containing orthogonal site selective recombinases (OSSRs)

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

Gilmore, Joshua M.; Anderson, J. Christopher; Dueber, John E.

The present invention provides for a recombinant nucleic acid comprising a nucleotide sequence comprising a plurality of constructs, wherein each construct independently comprises a nucleotide sequence of interest flanked by a pair of recombinase recognition sequences. Each pair of recombinase recognition sequences is recognized by a distinct recombinase. Optionally, each construct can, independently, further comprise one or more genes encoding a recombinase capable of recognizing the pair of recombinase recognition sequences of the construct. The recombinase can be an orthogonal (non-cross reacting), site-selective recombinase (OSSR).

Haptic perception and body representation in lateral and medial occipito-temporal cortices.

PubMed

Costantini, Marcello; Urgesi, Cosimo; Galati, Gaspare; Romani, Gian Luca; Aglioti, Salvatore M

2011-04-01

Although vision is the primary sensory modality that humans and other primates use to identify objects in the environment, we can recognize crucial object features (e.g., shape, size) using the somatic modality. Previous studies have shown that the occipito-temporal areas dedicated to the visual processing of object forms, faces and bodies also show category-selective responses when the preferred stimuli are haptically explored out of view. Visual processing of human bodies engages specific areas in lateral (extrastriate body area, EBA) and medial (fusiform body area, FBA) occipito-temporal cortex. This study aimed at exploring the relative involvement of EBA and FBA in the haptic exploration of body parts. During fMRI scanning, participants were asked to haptically explore either real-size fake body parts or objects. We found a selective activation of right and left EBA, but not of right FBA, while participants haptically explored body parts as compared to real objects. This suggests that EBA may integrate visual body representations with somatosensory information regarding body parts and form a multimodal representation of the body. Furthermore, both left and right EBA showed a comparable level of body selectivity during haptic perception and visual imagery. However, right but not left EBA was more activated during haptic exploration than visual imagery of body parts, ruling out that the response to haptic body exploration was entirely due to the use of visual imagery. Overall, the results point to the existence of different multimodal body representations in the occipito-temporal cortex which are activated during perception and imagery of human body parts. Copyright © 2011 Elsevier Ltd. All rights reserved.

Gently does it: Humans outperform a software classifier in recognizing subtle, nonstereotypical facial expressions.

PubMed

Yitzhak, Neta; Giladi, Nir; Gurevich, Tanya; Messinger, Daniel S; Prince, Emily B; Martin, Katherine; Aviezer, Hillel

2017-12-01

According to dominant theories of affect, humans innately and universally express a set of emotions using specific configurations of prototypical facial activity. Accordingly, thousands of studies have tested emotion recognition using sets of highly intense and stereotypical facial expressions, yet their incidence in real life is virtually unknown. In fact, a commonplace experience is that emotions are expressed in subtle and nonprototypical forms. Such facial expressions are at the focus of the current study. In Experiment 1, we present the development and validation of a novel stimulus set consisting of dynamic and subtle emotional facial displays conveyed without constraining expressers to using prototypical configurations. Although these subtle expressions were more challenging to recognize than prototypical dynamic expressions, they were still well recognized by human raters, and perhaps most importantly, they were rated as more ecological and naturalistic than the prototypical expressions. In Experiment 2, we examined the characteristics of subtle versus prototypical expressions by subjecting them to a software classifier, which used prototypical basic emotion criteria. Although the software was highly successful at classifying prototypical expressions, it performed very poorly at classifying the subtle expressions. Further validation was obtained from human expert face coders: Subtle stimuli did not contain many of the key facial movements present in prototypical expressions. Together, these findings suggest that emotions may be successfully conveyed to human viewers using subtle nonprototypical expressions. Although classic prototypical facial expressions are well recognized, they appear less naturalistic and may not capture the richness of everyday emotional communication. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Identification of antigenic Sarcoptes scabiei proteins for use in a diagnostic test and of non-antigenic proteins that may be immunomodulatory

PubMed Central

Morgan, Marjorie S.; Rider, S. Dean; Arlian, Larry G.

2017-01-01

Background Scabies, caused by the mite, Sarcoptes scabiei, infects millions of humans, and many wild and domestic mammals. Scabies mites burrow in the lower stratum corneum of the epidermis of the skin and are the source of substances that are antigenic or modulate aspects of the protective response of the host. Ordinary scabies is a difficult disease to diagnose. Objective The goal of this project was to identify S. scabiei proteins that may be candidate antigens for use in a diagnostic test or may be used by the mite to modulate the host’s protective response. Methods An aqueous extract of S. scabiei was separated by 2-dimensional electrophoresis and proteins were identified by mass spectrometry. A parallel immunoblot was probed with serum from patients with ordinary scabies to identify IgM and/or IgG-binding antigens. The genes coding for 23 selected proteins were cloned into E. coli and the expressed recombinant proteins were screened with serum from patients with confirmed ordinary scabies. Results We identified 50 different proteins produced by S. scabiei, 34 of which were not previously identified, and determined that 66% were recognized by patient IgM and/or IgG. Fourteen proteins were screened for use in a diagnostic test but none possessed enough sensitivity and specificity to be useful. Six of the 9 proteins selected for the possibility that they may be immunomodulatory were not recognized by antibodies in patient serum. Conclusions Thirty-three proteins that bound IgM and/or IgG from the serum of patients with ordinary scabies were identified. None of the 14 tested were useful for inclusion in a diagnostic test. The identities of 16 proteins that are not recognized as antigens by infected patients were also determined. These could be among the molecules that are responsible for this mite’s ability to modulate its host’s innate and adaptive immune responses. PMID:28604804

STK-1, the human homolog of Flk-2/Flt-3, is selectively expressed in CD34+ human bone marrow cells and is involved in the proliferation of early progenitor/stem cells.

PubMed Central

Small, D; Levenstein, M; Kim, E; Carow, C; Amin, S; Rockwell, P; Witte, L; Burrow, C; Ratajczak, M Z; Gewirtz, A M

1994-01-01

We cloned the cDNA for stem cell tyrosine kinase 1 (STK-1), the human homolog of murine Flk-2/Flt-3, from a CD34+ hematopoietic stem cell-enriched library and investigated its expression in subsets of normal human bone marrow. The cDNA encodes a protein of 993 aa with 85% identity and 92% similarity to Flk-2/Flt-3. STK-1 is a member of the type III receptor tyrosine kinase family that includes KIT (steel factor receptor), FMS (colony-stimulating factor 1R), and platelet-derived growth factor receptor. STK-1 expression in human blood and marrow is restricted to CD34+ cells, a population greatly enriched for stem/progenitor cells. Anti-STK-1 antiserum recognizes polypeptides of 160 and 130 kDa in several STK-1-expressing cell lines and in 3T3 cells transfected with a STK-1 expression vector. Antisense oligonucleotides directed against STK-1 sequences inhibited hematopoietic colony formation, most strongly in long-term bone marrow cultures. These data suggest that STK-1 may function as a growth factor receptor on hematopoietic stem and/or progenitor cells. Images Fig. 2 Fig. 3 Fig. 4 PMID:7507245

Production and characterization of a high-affinity nanobody against human endoglin.

PubMed

Ahmadvand, Davoud; Rasaee, Mohammad J; Rahbarizadeh, Fatemeh; Mohammadi, Mohammad

2008-10-01

Abstract Antibodies or antibody fragments are almost exclusively applied in human therapy and diagnosis. The high affinity and specificity of antibodies makes them suitable for these applications. Nanobody, the variable domain of Camelidae heavy chain antibodies, have superior properties compared with conventional antibodies in that they are small, non-immunogenic, very stable, highly soluble, and easy to produce in large quantities. In the present study, we report the isolation and characterization of a high-affinity binder against human endoglin retrieved from camels' nanobody gene library. Endoglin (CD105), an accessory protein of the transforming growth factor beta receptor complex, has become an attractive molecule for the targeting of the tumor vasculature. Upregulation of endoglin on proliferating endothelial cells is associated with tumor neovascularization. Here, we generated two nanobody gene libraries displayed on phage particles. Some single-domain antibody fragments have been isolated that specifically recognize the recombinant extracellular domain of human endoglin. The other selected anti-endoglin nanobody (AR1-86) showed strong binding to human endoglin expressing endothelial cells (HUVECs), while no binding was observed with the endoglin-negative cell line (HEK293). This high-affinity single-domain antibody could be a good candidate for the generation of vascular or tumor targeting agents in cancer therapy.

Anxiety disorders in adolescence are associated with impaired facial expression recognition to negative valence.

PubMed

Jarros, Rafaela Behs; Salum, Giovanni Abrahão; Belem da Silva, Cristiano Tschiedel; Toazza, Rudineia; de Abreu Costa, Marianna; Fumagalli de Salles, Jerusa; Manfro, Gisele Gus

2012-02-01

The aim of the present study was to test the ability of adolescents with a current anxiety diagnosis to recognize facial affective expressions, compared to those without an anxiety disorder. Forty cases and 27 controls were selected from a larger cross sectional community sample of adolescents, aged from 10 to 17 years old. Adolescent's facial recognition of six human emotions (sadness, anger, disgust, happy, surprise and fear) and neutral faces was assessed through a facial labeling test using Ekman's Pictures of Facial Affect (POFA). Adolescents with anxiety disorders had a higher mean number of errors in angry faces as compared to controls: 3.1 (SD=1.13) vs. 2.5 (SD=2.5), OR=1.72 (CI95% 1.02 to 2.89; p=0.040). However, they named neutral faces more accurately than adolescents without anxiety diagnosis: 15% of cases vs. 37.1% of controls presented at least one error in neutral faces, OR=3.46 (CI95% 1.02 to 11.7; p=0.047). No differences were found considering other human emotions or on the distribution of errors in each emotional face between the groups. Our findings support an anxiety-mediated influence on the recognition of facial expressions in adolescence. These difficulty in recognizing angry faces and more accuracy in naming neutral faces may lead to misinterpretation of social clues and can explain some aspects of the impairment in social interactions in adolescents with anxiety disorders. Copyright © 2011 Elsevier Ltd. All rights reserved.

THE DELICATE BALANCE BETWEEN SECRETED PROTEIN FOLDING AND ENDOPLASMIC RETICULUM-ASSOCIATED DEGRADATION IN HUMAN PHYSIOLOGY

PubMed Central

Guerriero, Christopher J.; Brodsky, Jeffrey L.

2014-01-01

Protein folding is a complex, error-prone process that often results in an irreparable protein by-product. These by-products can be recognized by cellular quality control machineries and targeted for proteasome-dependent degradation. The folding of proteins in the secretory pathway adds another layer to the protein folding “problem,” as the endoplasmic reticulum maintains a unique chemical environment within the cell. In fact, a growing number of diseases are attributed to defects in secretory protein folding, and many of these by-products are targeted for a process known as endoplasmic reticulum-associated degradation (ERAD). Since its discovery, research on the mechanisms underlying the ERAD pathway has provided new insights into how ERAD contributes to human health during both normal and diseases states. Links between ERAD and disease are evidenced from the loss of protein function as a result of degradation, chronic cellular stress when ERAD fails to keep up with misfolded protein production, and the ability of some pathogens to coopt the ERAD pathway. The growing number of ERAD substrates has also illuminated the differences in the machineries used to recognize and degrade a vast array of potential clients for this pathway. Despite all that is known about ERAD, many questions remain, and new paradigms will likely emerge. Clearly, the key to successful disease treatment lies within defining the molecular details of the ERAD pathway and in understanding how this conserved pathway selects and degrades an innumerable cast of substrates. PMID:22535891

Two types of aggression in human evolution.

PubMed

Wrangham, Richard W

2018-01-09

Two major types of aggression, proactive and reactive, are associated with contrasting expression, eliciting factors, neural pathways, development, and function. The distinction is useful for understanding the nature and evolution of human aggression. Compared with many primates, humans have a high propensity for proactive aggression, a trait shared with chimpanzees but not bonobos. By contrast, humans have a low propensity for reactive aggression compared with chimpanzees, and in this respect humans are more bonobo-like. The bimodal classification of human aggression helps solve two important puzzles. First, a long-standing debate about the significance of aggression in human nature is misconceived, because both positions are partly correct. The Hobbes-Huxley position rightly recognizes the high potential for proactive violence, while the Rousseau-Kropotkin position correctly notes the low frequency of reactive aggression. Second, the occurrence of two major types of human aggression solves the execution paradox, concerned with the hypothesized effects of capital punishment on self-domestication in the Pleistocene. The puzzle is that the propensity for aggressive behavior was supposedly reduced as a result of being selected against by capital punishment, but capital punishment is itself an aggressive behavior. Since the aggression used by executioners is proactive, the execution paradox is solved to the extent that the aggressive behavior of which victims were accused was frequently reactive, as has been reported. Both types of killing are important in humans, although proactive killing appears to be typically more frequent in war. The biology of proactive aggression is less well known and merits increased attention.

Real-time Human Activity Recognition

NASA Astrophysics Data System (ADS)

Albukhary, N.; Mustafah, Y. M.

2017-11-01

The traditional Closed-circuit Television (CCTV) system requires human to monitor the CCTV for 24/7 which is inefficient and costly. Therefore, there’s a need for a system which can recognize human activity effectively in real-time. This paper concentrates on recognizing simple activity such as walking, running, sitting, standing and landing by using image processing techniques. Firstly, object detection is done by using background subtraction to detect moving object. Then, object tracking and object classification are constructed so that different person can be differentiated by using feature detection. Geometrical attributes of tracked object, which are centroid and aspect ratio of identified tracked are manipulated so that simple activity can be detected.

Human XPA and RPA DNA repair proteins participate in specific recognition of triplex-induced helical distortions

NASA Astrophysics Data System (ADS)

Vasquez, Karen M.; Christensen, Jesper; Li, Lei; Finch, Rick A.; Glazer, Peter M.

2002-04-01

Nucleotide excision repair (NER) plays a central role in maintaining genomic integrity by detecting and repairing a wide variety of DNA lesions. Xeroderma pigmentosum complementation group A protein (XPA) is an essential component of the repair machinery, and it is thought to be involved in the initial step as a DNA damage recognition and/or confirmation factor. Human replication protein A (RPA) and XPA have been reported to interact to form a DNA damage recognition complex with greater specificity for damaged DNA than XPA alone. The mechanism by which these two proteins recognize such a wide array of structures resulting from different types of DNA damage is not known. One possibility is that they recognize a common feature of the lesions, such as distortions of the helical backbone. We have tested this idea by determining whether human XPA and RPA proteins can recognize the helical distortions induced by a DNA triple helix, a noncanonical DNA structure that has been shown to induce DNA repair, mutagenesis, and recombination. We measured binding of XPA and RPA, together or separately, to substrates containing triplexes with three, two, or no strands covalently linked by psoralen conjugation and photoaddition. We found that RPA alone recognizes all covalent triplex structures, but also forms multivalent nonspecific DNA aggregates at higher concentrations. XPA by itself does not recognize the substrates, but it binds them in the presence of RPA. Addition of XPA decreases the nonspecific DNA aggregate formation. These results support the hypothesis that the NER machinery is targeted to helical distortions and demonstrate that RPA can recognize damaged DNA even without XPA.

Episodic Reasoning for Vision-Based Human Action Recognition

PubMed Central

Martinez-del-Rincon, Jesus

2014-01-01

Smart Spaces, Ambient Intelligence, and Ambient Assisted Living are environmental paradigms that strongly depend on their capability to recognize human actions. While most solutions rest on sensor value interpretations and video analysis applications, few have realized the importance of incorporating common-sense capabilities to support the recognition process. Unfortunately, human action recognition cannot be successfully accomplished by only analyzing body postures. On the contrary, this task should be supported by profound knowledge of human agency nature and its tight connection to the reasons and motivations that explain it. The combination of this knowledge and the knowledge about how the world works is essential for recognizing and understanding human actions without committing common-senseless mistakes. This work demonstrates the impact that episodic reasoning has in improving the accuracy of a computer vision system for human action recognition. This work also presents formalization, implementation, and evaluation details of the knowledge model that supports the episodic reasoning. PMID:24959602

The heritage of pathogen pressures and ancient demography in the human innate-immunity CD209/CD209L region.

PubMed

Barreiro, Luis B; Patin, Etienne; Neyrolles, Olivier; Cann, Howard M; Gicquel, Brigitte; Quintana-Murci, Lluís

2005-11-01

The innate immunity system constitutes the first line of host defense against pathogens. Two closely related innate immunity genes, CD209 and CD209L, are particularly interesting because they directly recognize a plethora of pathogens, including bacteria, viruses, and parasites. Both genes, which result from an ancient duplication, possess a neck region, made up of seven repeats of 23 amino acids each, known to play a major role in the pathogen-binding properties of these proteins. To explore the extent to which pathogens have exerted selective pressures on these innate immunity genes, we resequenced them in a group of samples from sub-Saharan Africa, Europe, and East Asia. Moreover, variation in the number of repeats of the neck region was defined in the entire Human Genome Diversity Panel for both genes. Our results, which are based on diversity levels, neutrality tests, population genetic distances, and neck-region length variation, provide genetic evidence that CD209 has been under a strong selective constraint that prevents accumulation of any amino acid changes, whereas CD209L variability has most likely been shaped by the action of balancing selection in non-African populations. In addition, our data point to the neck region as the functional target of such selective pressures: CD209 presents a constant size in the neck region populationwide, whereas CD209L presents an excess of length variation, particularly in non-African populations. An additional interesting observation came from the coalescent-based CD209 gene tree, whose binary topology and time depth (approximately 2.8 million years ago) are compatible with an ancestral population structure in Africa. Altogether, our study has revealed that even a short segment of the human genome can uncover an extraordinarily complex evolutionary history, including different pathogen pressures on host genes as well as traces of admixture among archaic hominid populations.

A reverse-translational study of dysfunctional exploration in psychiatric disorders: from mice to men.

PubMed

Perry, William; Minassian, Arpi; Paulus, Martin P; Young, Jared W; Kincaid, Meegin J; Ferguson, Eliza J; Henry, Brook L; Zhuang, Xiaoxi; Masten, Virginia L; Sharp, Richard F; Geyer, Mark A

2009-10-01

Bipolar mania and schizophrenia are recognized as separate disorders but share many commonalities, which raises the question of whether they are the same disorder on different ends of a continuum. The lack of distinct endophenotypes of bipolar mania and schizophrenia has complicated the development of animal models that are specific to these disorders. Exploration is fundamental to survival and is dysregulated in these 2 disorders. Although exploratory behavior in rodents has been widely studied, surprisingly little work has examined this critical function in humans. To quantify the exploratory behavior of individuals with bipolar mania and schizophrenia and to identify distinctive phenotypes of these illnesses. Static group comparison by the use of a novel human open field paradigm, the human Behavioral Pattern Monitor (BPM). Psychiatric hospital. Fifteen patients with bipolar mania and 16 patients with schizophrenia were compared with 26 healthy volunteers in the human BPM. The effects of amphetamine sulfate, the selective dopamine transporter inhibitor GBR12909, and the genetic knockdown of the dopamine transporter were compared with controls in the mouse BPM. The amount of motor activity, spatial patterns of activity, and exploration of novel stimuli were quantified in both the human and mouse BPMs. Patients with bipolar mania demonstrated a unique exploratory pattern, characterized by high motor activity and increased object exploration. Patients with schizophrenia did not show the expected habituation of motor activity. Selective genetic or pharmacologic inhibition of the dopamine transporter matched the mania phenotype better than the effects of amphetamine, which has been the criterion standard for animal models of mania. These findings validate the human open field paradigm and identify defining characteristics of bipolar mania that are distinct from those of schizophrenia. This cross-species study of exploration calls into question an accepted animal model of mania and should help to develop more accurate human and animal models, which are essential to the identification of the neurobiological underpinnings of neuropsychiatric disorders.

A reverse translational study of dysfunctional exploration in psychiatric disorders: from mice to men

PubMed Central

Perry, William; Minassian, Arpi; Paulus, Martin P.; Young, Jared W.; Kincaid, Meegin J.; Ferguson, Eliza J.; Henry, Brook L.; Zhuang, Xiaoxi; Masten, Virginia L.; Sharp, Richard F.; Geyer, Mark A.

2009-01-01

Context Bipolar mania and schizophrenia are recognized as separate disorders but share many commonalities, raising the question of whether they are in fact the same disorder on different ends of a continuum. The lack of distinct endophenotypes of bipolar mania and schizophrenia has complicated the development of animal models that are specific to these disorders. Exploration is fundamental to survival and is dysregulated in these two disorders. Although exploratory behavior in rodents has been widely studied, surprisingly little work has examined this critical function in humans. Objective We used a novel human open field paradigm, the human Behavioral Pattern Monitor (BPM), to quantify exploratory behavior of individuals with bipolar mania and schizophrenia and to identify distinctive phenotypes of these illnesses. Design Static group comparison. Setting Psychiatric hospital. Participants 15 bipolar mania and 16 schizophrenia subjects were compared to 26 healthy volunteers in the human BPM. The effects of amphetamine, the selective dopamine transporter (DAT) inhibitor GBR12909, and genetic knockdown of the DAT were compared to controls in the mouse BPM. Measures The amount of motor activity, spatial patterns of activity, and exploration of novel stimuli were quantified in both the human and mouse BPMs. Results Bipolar manic subjects demonstrated a unique exploratory pattern, characterized by high motor activity and increased object exploration. Schizophrenia subjects did not show the expected habituation of motor activity. Selective genetic or pharmacological inhibition of the DAT matched the mania phenotype better than the “gold standard” model of mania (amphetamine). Conclusion These findings validate the human open field paradigm and identify defining characteristics of bipolar mania that are distinct from schizophrenia. This cross-species study of exploration calls into question an accepted animal model of mania and should help to develop more accurate human and animal models, which are essential to identify neurobiological underpinnings of neuropsychiatric disorders. PMID:19805697

Discrimination of Complex Human Behavior by Pigeons (Columba livia) and Humans

PubMed Central

Qadri, Muhammad A. J.; Sayde, Justin M.; Cook, Robert G.

2014-01-01

The cognitive and neural mechanisms for recognizing and categorizing behavior are not well understood in non-human animals. In the current experiments, pigeons and humans learned to categorize two non-repeating, complex human behaviors (“martial arts” vs. “Indian dance”). Using multiple video exemplars of a digital human model, pigeons discriminated these behaviors in a go/no-go task and humans in a choice task. Experiment 1 found that pigeons already experienced with discriminating the locomotive actions of digital animals acquired the discrimination more rapidly when action information was available than when only pose information was available. Experiments 2 and 3 found this same dynamic superiority effect with naïve pigeons and human participants. Both species used the same combination of immediately available static pose information and more slowly perceived dynamic action cues to discriminate the behavioral categories. Theories based on generalized visual mechanisms, as opposed to embodied, species-specific action networks, offer a parsimonious account of how these different animals recognize behavior across and within species. PMID:25379777

The Isolation of Novel Phage Display-Derived Human Recombinant Antibodies Against CCR5, the Major Co-Receptor of HIV

PubMed Central

Shimoni, Moria; Herschhorn, Alon; Britan-Rosich, Yelena; Kotler, Moshe; Benhar, Itai

2013-01-01

Abstract Selecting for antibodies against specific cell-surface proteins is a difficult task due to many unrelated proteins that are expressed on the cell surface. Here, we describe a method to screen antibody-presenting phage libraries against native cell-surface proteins. We applied this method to isolate antibodies that selectively recognize CCR5, which is the major co-receptor for HIV entry (consequently, playing a pivotal role in HIV transmission and pathogenesis). We employed a phage screening strategy by using cells that co-express GFP and CCR5, along with an excess of control cells that do not express these proteins (and are otherwise identical to the CCR5-expressing cells). These control cells are intended to remove most of the phages that bind the cells nonspecifically; thus leading to an enrichment of the phages presenting anti-CCR5-specific antibodies. Subsequently, the CCR5-presenting cells were quantitatively sorted by flow cytometry, and the bound phages were eluted, amplified, and used for further successive selection rounds. Several different clones of human single-chain Fv antibodies that interact with CCR5-expressing cells were identified. The most specific monoclonal antibody was converted to a full-length IgG and bound the second extracellular loop of CCR5. The experimental approach presented herein for screening for CCR5-specific antibodies can be applicable to screen antibody-presenting phage libraries against any cell-surface expressed protein of interest. PMID:23941674

Genotoxicity assessment of a selected cytostatic drug mixture in human lymphocytes: A study based on concentrations relevant for occupational exposure.

PubMed

Gajski, Goran; Ladeira, Carina; Gerić, Marko; Garaj-Vrhovac, Vera; Viegas, Susana

2018-02-01

Cytostatic drugs are highly cytotoxic agents used in cancer treatment and although their benefit is unquestionable, they have been recognized as hazardous to healthcare professionals in occupational settings. In a working environment, simultaneous exposure to cytostatics may occur creating a higher risk than that of a single substance. Hence, the present study evaluated the combined cyto/genotoxicity of a mixture of selected cytostatics with different mechanisms of action (MoA; 5-fluorouracil, cyclophosphamide and paclitaxel) towards human lymphocytes in vitro at a concentration range relevant for occupational as well as environmental exposure. The results suggest that the selected cytostatic drug mixture is potentially cyto/genotoxic and that it can induce cell and genome damage even at low concentrations. This indicates not only that such mixture may pose a risk to cell and genome integrity, but also that single compound toxicity data are not sufficient for the prediction of toxicity in a complex working environment. The presence of drugs in different amounts and with different MoA suggests the need to study the relationship between the presence of genotoxic components in the mixture and the resulting effects, taking into account the MoA of each component by itself. Therefore, this study provides new data sets necessary for scientifically-based risk assessments of cytostatic drug mixtures in occupational as well as environmental settings. Copyright © 2017 Elsevier Inc. All rights reserved.

Improving The Discipline of Cost Estimation and Analysis

NASA Technical Reports Server (NTRS)

Piland, William M.; Pine, David J.; Wilson, Delano M.

2000-01-01

The need to improve the quality and accuracy of cost estimates of proposed new aerospace systems has been widely recognized. The industry has done the best job of maintaining related capability with improvements in estimation methods and giving appropriate priority to the hiring and training of qualified analysts. Some parts of Government, and National Aeronautics and Space Administration (NASA) in particular, continue to need major improvements in this area. Recently, NASA recognized that its cost estimation and analysis capabilities had eroded to the point that the ability to provide timely, reliable estimates was impacting the confidence in planning many program activities. As a result, this year the Agency established a lead role for cost estimation and analysis. The Independent Program Assessment Office located at the Langley Research Center was given this responsibility. This paper presents the plans for the newly established role. Described is how the Independent Program Assessment Office, working with all NASA Centers, NASA Headquarters, other Government agencies, and industry, is focused on creating cost estimation and analysis as a professional discipline that will be recognized equally with the technical disciplines needed to design new space and aeronautics activities. Investments in selected, new analysis tools, creating advanced training opportunities for analysts, and developing career paths for future analysts engaged in the discipline are all elements of the plan. Plans also include increasing the human resources available to conduct independent cost analysis of Agency programs during their formulation, to improve near-term capability to conduct economic cost-benefit assessments, to support NASA management's decision process, and to provide cost analysis results emphasizing "full-cost" and "full-life cycle" considerations. The Agency cost analysis improvement plan has been approved for implementation starting this calendar year. Adequate financial and human resources are being made available to accomplish the goals of this important effort, and all indications are that NASA's cost estimation and analysis core competencies will be substantially improved within the foreseeable future.

Development of a Mouse Monoclonal Antibody Cocktail for Post-exposure Rabies Prophylaxis in Humans

PubMed Central

Müller, Thomas; Dietzschold, Bernhard; Ertl, Hildegund; Fooks, Anthony R.; Freuling, Conrad; Fehlner-Gardiner, Christine; Kliemt, Jeannette; Meslin, Francois X.; Rupprecht, Charles E.; Tordo, Noël; Wanderler, Alexander I.; Kieny, Marie Paule

2009-01-01

As the demand for rabies post-exposure prophylaxis (PEP) treatments has increased exponentially in recent years, the limited supply of human and equine rabies immunoglobulin (HRIG and ERIG) has failed to provide the required passive immune component in PEP in countries where canine rabies is endemic. Replacement of HRIG and ERIG with a potentially cheaper and efficacious alternative biological for treatment of rabies in humans, therefore, remains a high priority. In this study, we set out to assess a mouse monoclonal antibody (MoMAb) cocktail with the ultimate goal to develop a product at the lowest possible cost that can be used in developing countries as a replacement for RIG in PEP. Five MoMAbs, E559.9.14, 1112-1, 62-71-3, M727-5-1, and M777-16-3, were selected from available panels based on stringent criteria, such as biological activity, neutralizing potency, binding specificity, spectrum of neutralization of lyssaviruses, and history of each hybridoma. Four of these MoMAbs recognize epitopes in antigenic site II and one recognizes an epitope in antigenic site III on the rabies virus (RABV) glycoprotein, as determined by nucleotide sequence analysis of the glycoprotein gene of unique MoMAb neutralization-escape mutants. The MoMAbs were produced under Good Laboratory Practice (GLP) conditions. Unique combinations (cocktails) were prepared, using different concentrations of the MoMAbs that were capable of targeting non-overlapping epitopes of antigenic sites II and III. Blind in vitro efficacy studies showed the MoMab cocktails neutralized a broad spectrum of lyssaviruses except for lyssaviruses belonging to phylogroups II and III. In vivo, MoMAb cocktails resulted in protection as a component of PEP that was comparable to HRIG. In conclusion, all three novel combinations of MoMAbs were shown to have equal efficacy to HRIG and therefore could be considered a potentially less expensive alternative biological agent for use in PEP and prevention of rabies in humans. PMID:19888334

Bioelectronic nose and its application to smell visualization.

PubMed

Ko, Hwi Jin; Park, Tai Hyun

2016-01-01

There have been many trials to visualize smell using various techniques in order to objectively express the smell because information obtained from the sense of smell in human is very subjective. So far, well-trained experts such as a perfumer, complex and large-scale equipment such as GC-MS, and an electronic nose have played major roles in objectively detecting and recognizing odors. Recently, an optoelectronic nose was developed to achieve this purpose, but some limitations regarding the sensitivity and the number of smells that can be visualized still persist. Since the elucidation of the olfactory mechanism, numerous researches have been accomplished for the development of a sensing device by mimicking human olfactory system. Engineered olfactory cells were constructed to mimic the human olfactory system, and the use of engineered olfactory cells for smell visualization has been attempted with the use of various methods such as calcium imaging, CRE reporter assay, BRET, and membrane potential assay; however, it is not easy to consistently control the condition of cells and it is impossible to detect low odorant concentration. Recently, the bioelectronic nose was developed, and much improved along with the improvement of nano-biotechnology. The bioelectronic nose consists of the following two parts: primary transducer and secondary transducer. Biological materials as a primary transducer improved the selectivity of the sensor, and nanomaterials as a secondary transducer increased the sensitivity. Especially, the bioelectronic noses using various nanomaterials combined with human olfactory receptors or nanovesicles derived from engineered olfactory cells have a potential which can detect almost all of the smells recognized by human because an engineered olfactory cell might be able to express any human olfactory receptor as well as can mimic human olfactory system. Therefore, bioelectronic nose will be a potent tool for smell visualization, but only if two technologies are completed. First, a multi-channel array-sensing system has to be applied for the integration of all of the olfactory receptors into a single chip for mimicking the performance of human nose. Second, the processing technique of the multi-channel system signals should be simultaneously established with the conversion of the signals to visual images. With the use of this latest sensing technology, the realization of a proper smell-visualization technology is expected in the near future.

Comparing human pancreatic cell secretomes by in vitro aptamer selection identifies cyclophilin B as a candidate pancreatic cancer biomarker

PubMed Central

Ray, Partha; Rialon-Guevara, Kristy L.; Veras, Emanuela; Sullenger, Bruce A.; White, Rebekah R.

2012-01-01

Most cases of pancreatic cancer are not diagnosed until they are no longer curable with surgery. Therefore, it is critical to develop a sensitive, preferably noninvasive, method for detecting the disease at an earlier stage. In order to identify biomarkers for pancreatic cancer, we devised an in vitro positive/negative selection strategy to identify RNA ligands (aptamers) that could detect structural differences between the secretomes of pancreatic cancer and non-cancerous cells. Using this molecular recognition approach, we identified an aptamer (M9-5) that differentially bound conditioned media from cancerous and non-cancerous human pancreatic cell lines. This aptamer further discriminated between the sera of pancreatic cancer patients and healthy volunteers with high sensitivity and specificity. We utilized biochemical purification methods and mass-spectrometric analysis to identify the M9-5 target as cyclophilin B (CypB). This molecular recognition–based strategy simultaneously identified CypB as a serum biomarker and generated a new reagent to recognize it in body fluids. Moreover, this approach should be generalizable to other diseases and complementary to traditional approaches that focus on differences in expression level between samples. Finally, we suggest that the aptamer we identified has the potential to serve as a tool for the early detection of pancreatic cancer. PMID:22484812

Comparing human pancreatic cell secretomes by in vitro aptamer selection identifies cyclophilin B as a candidate pancreatic cancer biomarker.

PubMed

Ray, Partha; Rialon-Guevara, Kristy L; Veras, Emanuela; Sullenger, Bruce A; White, Rebekah R

2012-05-01

Most cases of pancreatic cancer are not diagnosed until they are no longer curable with surgery. Therefore, it is critical to develop a sensitive, preferably noninvasive, method for detecting the disease at an earlier stage. In order to identify biomarkers for pancreatic cancer, we devised an in vitro positive/negative selection strategy to identify RNA ligands (aptamers) that could detect structural differences between the secretomes of pancreatic cancer and non-cancerous cells. Using this molecular recognition approach, we identified an aptamer (M9-5) that differentially bound conditioned media from cancerous and non-cancerous human pancreatic cell lines. This aptamer further discriminated between the sera of pancreatic cancer patients and healthy volunteers with high sensitivity and specificity. We utilized biochemical purification methods and mass-spectrometric analysis to identify the M9-5 target as cyclophilin B (CypB). This molecular recognition-based strategy simultaneously identified CypB as a serum biomarker and generated a new reagent to recognize it in body fluids. Moreover, this approach should be generalizable to other diseases and complementary to traditional approaches that focus on differences in expression level between samples. Finally, we suggest that the aptamer we identified has the potential to serve as a tool for the early detection of pancreatic cancer.

Character complexity and redundancy in writing systems over human history.

PubMed

Changizi, Mark A; Shimojo, Shinsuke

2005-02-07

A writing system is a visual notation system wherein a repertoire of marks, or strokes, is used to build a repertoire of characters. Are there any commonalities across writing systems concerning the rules governing how strokes combine into characters; commonalities that might help us identify selection pressures on the development of written language? In an effort to answer this question we examined how strokes combine to make characters in more than 100 writing systems over human history, ranging from about 10 to 200 characters,and including numerals, abjads, abugidas, alphabets and syllabaries from five major taxa: Ancient Near-Eastern, European, Middle Eastern, South Asian, Southeast Asian. We discovered underlying similarities in two fundamental respects. (i) The number of strokes per characters is approximately three, independent of the number of characters in the writing system; numeral systems are the exception, having on average only two strokes per character. (ii) Characters are ca. 50% redundant, independent of writing system size; intuitively, this means that acharacter's identity can be determined even when half of its strokes are removed. Because writing systems are under selective pressure to have characters that are easy for the visual system to recognize and for the motor system to write, these fundamental commonalities may be a fingerprint of mechanisms underlying the visuo-motor system.

Character complexity and redundancy in writing systems over human history

PubMed Central

Changizi, Mark A.; Shimojo, Shinsuke

2005-01-01

A writing system is a visual notation system wherein a repertoire of marks, or strokes, is used to build a repertoire of characters. Are there any commonalities across writing systems concerning the rules governing how strokes combine into characters; commonalities that might help us identify selection pressures on the development of written language? In an effort to answer this question we examined how strokes combine to make characters in more than 100 writing systems over human history, ranging from about 10 to 200 characters, and including numerals, abjads, abugidas, alphabets and syllabaries from five major taxa: Ancient Near-Eastern, European, Middle Eastern, South Asian, Southeast Asian. We discovered underlying similarities in two fundamental respects.The number of strokes per characters is approximately three, independent of the number of characters in the writing system; numeral systems are the exception, having on average only two strokes per character.Characters are ca. 50% redundant, independent of writing system size; intuitively, this means that a character’s identity can be determined even when half of its strokes are removed.Because writing systems are under selective pressure to have characters that are easy for the visual system to recognize and for the motor system to write, these fundamental commonalities may be a fingerprint of mechanisms underlying the visuo–motor system. PMID:15705551

Impact of HLA diversity on donor selection in organ and stem cell transplantation.

PubMed

Tiercy, Jean-Marie; Claas, Frans

2013-01-01

The human major histocompatibility complex is a multigene system encoding polymorphic human leucocyte antigens (HLA) that present peptides derived from pathogens to the immune system. The high diversity of HLA alleles and haplotypes in the worldwide populations represents a major barrier to organ and allogeneic hematopoietic stem cell transplantation, because HLA incompatibilities are efficiently recognized by T and B lymphocytes. In organ transplantation, pre-transplant anti-HLA antibodies need to be taken into account for organ allocation. Although HLA-incompatible transplants can be performed thanks to immunosuppressive drugs, the de novo production of anti-HLA antibodies still represents a major cause of graft failure. The HLAMatchmaker computer algorithm determines the immunogenicity of HLA mismatches and allows to define HLA antigens that will not induce an antibody response. Because of the much higher stringency of HLA compatibility criteria in stem cell transplantation, the best donor is a HLA genotypically identical sibling. However, more than 50% of the transplants are now performed with hematopoietic stem cells from volunteer donors selected from the international registry. The development of European national registries covering populations with different HLA haplotype frequencies is essential for optimizing donor search algorithms and providing the best chance for European patients to find a fully compatible donor.

21 CFR 182.8223 - Calcium pyrophosphate.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Calcium pyrophosphate. 182.8223 Section 182.8223... FOR HUMAN CONSUMPTION (CONTINUED) SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients § 182.8223 Calcium pyrophosphate. (a) Product. Calcium pyrophosphate. (b) Conditions of use. This substance is generally recognized...

21 CFR 182.8223 - Calcium pyrophosphate.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Calcium pyrophosphate. 182.8223 Section 182.8223... FOR HUMAN CONSUMPTION (CONTINUED) SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients § 182.8223 Calcium pyrophosphate. (a) Product. Calcium pyrophosphate. (b) Conditions of use. This substance is generally recognized...

A triaxial accelerometer-based physical-activity recognition via augmented-signal features and a hierarchical recognizer.

PubMed

Khan, Adil Mehmood; Lee, Young-Koo; Lee, Sungyoung Y; Kim, Tae-Seong

2010-09-01

Physical-activity recognition via wearable sensors can provide valuable information regarding an individual's degree of functional ability and lifestyle. In this paper, we present an accelerometer sensor-based approach for human-activity recognition. Our proposed recognition method uses a hierarchical scheme. At the lower level, the state to which an activity belongs, i.e., static, transition, or dynamic, is recognized by means of statistical signal features and artificial-neural nets (ANNs). The upper level recognition uses the autoregressive (AR) modeling of the acceleration signals, thus, incorporating the derived AR-coefficients along with the signal-magnitude area and tilt angle to form an augmented-feature vector. The resulting feature vector is further processed by the linear-discriminant analysis and ANNs to recognize a particular human activity. Our proposed activity-recognition method recognizes three states and 15 activities with an average accuracy of 97.9% using only a single triaxial accelerometer attached to the subject's chest.

Autonomous learning in gesture recognition by using lobe component analysis

NASA Astrophysics Data System (ADS)

Lu, Jian; Weng, Juyang

2007-02-01

Gesture recognition is a new human-machine interface method implemented by pattern recognition(PR).In order to assure robot safety when gesture is used in robot control, it is required to implement the interface reliably and accurately. Similar with other PR applications, 1) feature selection (or model establishment) and 2) training from samples, affect the performance of gesture recognition largely. For 1), a simple model with 6 feature points at shoulders, elbows, and hands, is established. The gestures to be recognized are restricted to still arm gestures, and the movement of arms is not considered. These restrictions are to reduce the misrecognition, but are not so unreasonable. For 2), a new biological network method, called lobe component analysis(LCA), is used in unsupervised learning. Lobe components, corresponding to high-concentrations in probability of the neuronal input, are orientation selective cells follow Hebbian rule and lateral inhibition. Due to the advantage of LCA method for balanced learning between global and local features, large amount of samples can be used in learning efficiently.

Development of a carbazole-based fluorescence probe for G-quadruplex DNA: The importance of side-group effect on binding specificity

NASA Astrophysics Data System (ADS)

Wang, Ming-Qi; Ren, Gui-Ying; Zhao, Shuang; Lian, Guang-Chang; Chen, Ting-Ting; Ci, Yang; Li, Hong-Yao

2018-06-01

G-quadruplex DNAs are highly prevalent in the human genome and involved in many important biological processes. However, many aspects of their biological mechanism and significance still need to be elucidated. Therefore, the development of fluorescent probes for G-quadruplex detection is important for the basic research. We report here on the development of small molecular dyes designed on the basis of carbazole scaffold by introducing styrene-like substituents at its 9-position, for the purpose of G-quadruplex recognition. Results revealed that the side group on the carbazole scaffold was very important for their ability to selectively recognize G-quadruplex DNA structures. 1a with the pyridine side group displayed excellent fluorescence signal turn-on property for the specific discrimination of G-quadruplex DNAs against other nucleic acids. The characteristics of 1a were further investigated with UV-vis spectrophotometry, fluorescence, circular dichroism, FID assay and molecular docking to validate the selectivity, sensitivity and detailed binding mode toward G-quadruplex DNAs.

[Screening specific recognition motif of RNA-binding proteins by SELEX in combination with next-generation sequencing technique].

PubMed

Zhang, Lu; Xu, Jinhao; Ma, Jinbiao

2016-07-25

RNA-binding protein exerts important biological function by specifically recognizing RNA motif. SELEX (Systematic evolution of ligands by exponential enrichment), an in vitro selection method, can obtain consensus motif with high-affinity and specificity for many target molecules from DNA or RNA libraries. Here, we combined SELEX with next-generation sequencing to study the protein-RNA interaction in vitro. A pool of RNAs with 20 bp random sequences were transcribed by T7 promoter, and target protein was inserted into plasmid containing SBP-tag, which can be captured by streptavidin beads. Through only one cycle, the specific RNA motif can be obtained, which dramatically improved the selection efficiency. Using this method, we found that human hnRNP A1 RRMs domain (UP1 domain) bound RNA motifs containing AGG and AG sequences. The EMSA experiment indicated that hnRNP A1 RRMs could bind the obtained RNA motif. Taken together, this method provides a rapid and effective method to study the RNA binding specificity of proteins.

[Peptide phage display in biotechnology and biomedicine].

PubMed

Kuzmicheva, G A; Belyavskaya, V A

2016-07-01

To date peptide phage display is one of the most common combinatorial methods used for identifying specific peptide ligands. Phage display peptide libraries containing billions different clones successfully used for selection of ligands with high affinity and selectivity toward wide range of targets including individual proteins, bacteria, viruses, spores, different kind of cancer cells and variety of nonorganic targets (metals, alloys, semiconductors etc.) Success of using filamentous phage in phage display technologies relays on the robustness of phage particles and a possibility to genetically modify its DNA to construct new phage variants with novel properties. In this review we are discussing characteristics of the most known non-commercial peptide phage display libraries of different formats (landscape libraries in particular) and their successful applications in several fields of biotechnology and biomedicine: discovery of peptides with diagnostic values against different pathogens, discovery and using of peptides recognizing cancer cells, trends in using of phage display technologies in human interactome studies, application of phage display technologies in construction of novel nano materials.

Allosteric ligands for the pharmacologically dark receptors GPR68 and GPR65

PubMed Central

Huang, Xi-Ping; Karpiak, Joel; Kroeze, Wesley K.; Zhu, Hu; Chen, Xin; Moy, Sheryl S.; Saddoris, Kara A.; Nikolova, Viktoriya; Farrell, Martilias S.; Wang, Sheng; Mangano, Thomas J.; Deshpande, Deepak A.; Jiang, Alice; Penn, Raymond B.; Jin, Jian; Koller, Beverly H.; Kenakin, Terry; Shoichet, Brian K.; Roth, Bryan L.

2016-01-01

At least 120 non-olfactory G protein-coupled receptors in the human genome are ”orphans” for which endogenous ligands are unknown, and many have no selective ligands, hindering elucidation of their biological functions and clinical relevance. Among these is GPR68, a proton receptor that lacks small molecule modulators for probing its biology. Yeast-based screens against GPR68 identified the benzodiazepine drug lorazepam as a non-selective GPR68 positive allosteric modulator. Over 3000 GPR68 homology models were refined to recognize lorazepam in a putative allosteric site. Docking 3.1 million molecules predicted new GPR68 modulators many of which were confirmed in functional assays. One potent GPR68 modulator—ogerin– suppressed recall in fear conditioning in wild-type, but not in GPR68 knockout mice. The same approach led to the discovery of allosteric agonists and negative allosteric modulators for GPR65. Combining physical and structure-based screening may be broadly useful for ligand discovery for understudied and orphan GPCRs. PMID:26550826

Effects of space flight exposure on cell growth, tumorigenicity and gene expression in cancer cells

NASA Astrophysics Data System (ADS)

Yang, Cheng; Li, Yuehui; Zhang, Zhijie; Luo, Chen; Tong, Yongqing; Zhou, Guohua; Xie, Pingli; Hu, Jinyue; Li, Guancheng

2008-12-01

It is well recognized that harsh outer space environment, consisting of microgravity and radiation, poses significant health risks for human cells. To investigate potential effects of the space environment exposure on cancer cells we examined the biological changes in Caski cells carried by the "Shen Zhou IV" spaceship. After exposure for 7 days in spaceflight, 1440 survival subclonal cell lines were established and 4 cell lines were screened. 44F10 and 17E3 were selected because of their increased cell proliferation and tumorigenesis, while 48A9 and 31F2 had slower cytological events. Experiments with cell proliferation assay, flow cytometry, soft agar assay, tumorigenesis assay and DNA microarray analysis have shown that selected cell lines presented multiple biological changes in cell morphology, cell growth, tumorigenicity and gene expression. These results suggest that space environment exposure can make significant biological impact on cancer cells and provide an entry point to find the immunological target of tumorigenesis.

Protozoacidal Trojan-Horse: Use of a Ligand-Lytic Peptide for Selective Destruction of Symbiotic Protozoa within Termite Guts

PubMed Central

Sethi, Amit; Delatte, Jennifer; Foil, Lane; Husseneder, Claudia

2014-01-01

For novel biotechnology-based termite control, we developed a cellulose bait containing freeze-dried genetically engineered yeast which expresses a protozoacidal lytic peptide attached to a protozoa-recognizing ligand. The yeast acts as a ‘Trojan-Horse’ that kills the cellulose-digesting protozoa in the termite gut, which leads to the death of termites, presumably due to inefficient cellulose digestion. The ligand targets the lytic peptide specifically to protozoa, thereby increasing its protozoacidal efficiency while protecting non-target organisms. After ingestion of the bait, the yeast propagates in the termite's gut and is spread throughout the termite colony via social interactions. This novel paratransgenesis-based strategy could be a good supplement for current termite control using fortified biological control agents in addition to chemical insecticides. Moreover, this ligand-lytic peptide system could be used for drug development to selectively target disease-causing protozoa in humans or other vertebrates. PMID:25198727

Foundations to the unified psycho-cognitive engine.

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

Bernard, Michael Lewis; Bier, Asmeret Brooke; Backus, George A.

This document outlines the key features of the SNL psychological engine. The engine is designed to be a generic presentation of cognitive entities interacting among themselves and with the external world. The engine combines the most accepted theories of behavioral psychology with those of behavioral economics to produce a unified simulation of human response from stimuli through executed behavior. The engine explicitly recognizes emotive and reasoned contributions to behavior and simulates the dynamics associated with cue processing, learning, and choice selection. Most importantly, the model parameterization can come from available media or survey information, as well subject-matter-expert information. The frameworkmore » design allows the use of uncertainty quantification and sensitivity analysis to manage confidence in using the analysis results for intervention decisions.« less

An Interactive Astronaut-Robot System with Gesture Control

PubMed Central

Liu, Jinguo; Luo, Yifan; Ju, Zhaojie

2016-01-01

Human-robot interaction (HRI) plays an important role in future planetary exploration mission, where astronauts with extravehicular activities (EVA) have to communicate with robot assistants by speech-type or gesture-type user interfaces embedded in their space suits. This paper presents an interactive astronaut-robot system integrating a data-glove with a space suit for the astronaut to use hand gestures to control a snake-like robot. Support vector machine (SVM) is employed to recognize hand gestures and particle swarm optimization (PSO) algorithm is used to optimize the parameters of SVM to further improve its recognition accuracy. Various hand gestures from American Sign Language (ASL) have been selected and used to test and validate the performance of the proposed system. PMID:27190503

Metabolic traits of pathogenic streptococci.

PubMed

Willenborg, Jörg; Goethe, Ralph

2016-11-01

Invasive and noninvasive diseases caused by facultative pathogenic streptococci depend on their equipment with virulence factors and on their ability to sense and adapt to changing nutrients in different host environments. The knowledge of the principal metabolic mechanisms which allow these bacteria to recognize and utilize nutrients in host habitats is a prerequisite for our understanding of streptococcal pathogenicity and the development of novel control strategies. This review aims to summarize and compare the central carbohydrate metabolic and amino acid biosynthetic pathways of a selected group of streptococcal species, all belonging to the naso-oropharyngeal microbiome in humans and/or animals. We also discuss the urgent need of comprehensive metabolomics approaches for a better understanding of the streptococcal metabolism during host-pathogen interaction. © 2016 Federation of European Biochemical Societies.

Acute and chronic systemic chromium toxicity.

PubMed

Gad, S C

1989-10-01

Although chromium and compounds containing it have been recognized as having potential severe adverse effects on health for more than 160 years, understanding of the systemic toxicology and true hazard of these compounds is still not complete. A review of the current state of knowledge is attempted in this paper, with appropriate attention given to the complications of multiple valence states and solubility. Selected chromium compounds, particularly hexavalent ones, are carcinogens, corrosives, delayed contact sensitizers, and have the kidney as their primary target organ. But chromium is also an essential element for humans. The body clearly possesses some effective detoxification mechanisms for some degree of exposure to hexavalent chrome compounds. The significant features of acute and chronic chromium toxicity are presented in view of these considerations.

A high affinity monoclonal antibody recognizing the light chain of human coagulating factor VII.

PubMed

Sarial, Sheila; Asadi, Farzad; Jeddi-Tehrani, Mahmood; Hadavi, Reza; Bayat, Ali Ahmad; Mahmoudian, Jafar; Taghizadeh-Jahed, Masoud; Shokri, Fazel; Rabbani, Hodjattallah

2012-12-01

Factor VII (FVII) is a serine protease-coagulating element responsible for the initiation of an extrinsic pathway of clot formation. Here we generated and characterized a high affinity monoclonal antibody that specifically recognizes human FVII. Recombinant human FVII (rh-FVII) was used for the production of a monoclonal antibody using BALB/c mice. The specificity of the antibody was determined by Western blot using plasma samples from human, mouse, sheep, goat, bovine, rabbit, and rat. Furthermore, the antibody was used to detect transiently expressed rh-FVII in BHK21 cell line using Western blot and sandwich ELISA. A mouse IgG1 (kappa chain) monoclonal antibody clone 1F1-B11 was produced against rh-FVII. The affinity constant (K(aff)) of the antibody was calculated to be 6.4×10(10) M(-1). The antibody could specifically recognize an epitope on the light chain of hFVII, with no reactivity with factor VII from several other animals. In addition, transiently expressed rh-FVII in BHK21 cells was recognized by 1F1-B11. The high affinity as well as the specificity of 1F1-B11 for hFVII will facilitate the affinity purification of hFVII and also production of FVII deficient plasma and minimizes the risk of bovine FVII contamination when fetal bovine serum-supplemented media are used for production and subsequent purification of rh-FVII.

Methods for Selecting Phage Display Antibody Libraries.

PubMed

Jara-Acevedo, Ricardo; Diez, Paula; Gonzalez-Gonzalez, Maria; Degano, Rosa Maria; Ibarrola, Nieves; Gongora, Rafael; Orfao, Alberto; Fuentes, Manuel

2016-01-01

The selection process aims sequential enrichment of phage antibody display library in clones that recognize the target of interest or antigen as the library undergoes successive rounds of selection. In this review, selection methods most commonly used for phage display antibody libraries have been comprehensively described. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Genome-Scale Protein Microarray Comparison of Human Antibody Responses in Plasmodium vivax Relapse and Reinfection.

PubMed

Chuquiyauri, Raul; Molina, Douglas M; Moss, Eli L; Wang, Ruobing; Gardner, Malcolm J; Brouwer, Kimberly C; Torres, Sonia; Gilman, Robert H; Llanos-Cuentas, Alejandro; Neafsey, Daniel E; Felgner, Philip; Liang, Xiaowu; Vinetz, Joseph M

2015-10-01

Large scale antibody responses in Plasmodium vivax malaria remains unexplored in the endemic setting. Protein microarray analysis of asexual-stage P. vivax was used to identify antigens recognized in sera from residents of hypoendemic Peruvian Amazon. Over 24 months, of 106 participants, 91 had two symptomatic P. vivax malaria episodes, 11 had three episodes, 3 had four episodes, and 1 had five episodes. Plasmodium vivax relapse was distinguished from reinfection by a merozoite surface protein-3α restriction fragment length polymorphism polymerase chain reaction (MSP3α PCR-RFLP) assay. Notably, P. vivax reinfection subjects did not have higher reactivity to the entire set of recognized P. vivax blood-stage antigens than relapse subjects, regardless of the number of malaria episodes. The most highly recognized P. vivax proteins were MSP 4, 7, 8, and 10 (PVX_003775, PVX_082650, PVX_097625, and PVX_114145); sexual-stage antigen s16 (PVX_000930); early transcribed membrane protein (PVX_090230); tryptophan-rich antigen (Pv-fam-a) (PVX_092995); apical merozoite antigen 1 (PVX_092275); and proteins of unknown function (PVX_081830, PVX_117680, PVX_118705, PVX_121935, PVX_097730, PVX_110935, PVX_115450, and PVX_082475). Genes encoding reactive proteins exhibited a significant enrichment of non-synonymous nucleotide variation, an observation suggesting immune selection. These data identify candidates for seroepidemiological tools to support malaria elimination efforts in P. vivax-endemic regions. © The American Society of Tropical Medicine and Hygiene.

Rethinking the area of protection "natural resources" in life cycle assessment.

PubMed

Dewulf, Jo; Benini, Lorenzo; Mancini, Lucia; Sala, Serenella; Blengini, Gian Andrea; Ardente, Fulvio; Recchioni, Marco; Maes, Joachim; Pant, Rana; Pennington, David

2015-05-05

Life cycle impact assessment (LCIA) in classical life cycle assessment (LCA) aims at analyzing potential impacts of products and services typically on three so-called areas of protection (AoPs): Natural Environment, Human Health, and Natural Resources. This paper proposes an elaboration of the AoP Natural Resources. It starts with analyzing different perspectives on Natural Resources as they are somehow sandwiched in between the Natural Environment (their cradle) and the human-industrial environment (their application). Reflecting different viewpoints, five perspectives are developed with the suggestion to select three in function of classical LCA. They result in three safeguard subjects: the Asset of Natural Resources, their Provisioning Capacity, and their role in Global Functions. Whereas the Provisioning Capacity is fully in function of humans, the global functions go beyond provisioning as they include nonprovisioning functions for humans and regulating and maintenance services for the globe as a whole, following the ecosystem services framework. A fourth and fifth safeguard subject has been identified: recognizing the role Natural Resources for human welfare, either specifically as building block in supply chains of products and services as such, either with or without their functions beyond provisioning. But as these are far broader as they in principle should include characterization of mechanisms within the human industrial society, they are considered as subjects for an integrated sustainability assessment (LCSA: life cycle sustainability assessment), that is, incorporating social, economic and environmental issues.

Duplex Bioelectronic Tongue for Sensing Umami and Sweet Tastes Based on Human Taste Receptor Nanovesicles.

PubMed

Ahn, Sae Ryun; An, Ji Hyun; Song, Hyun Seok; Park, Jin Wook; Lee, Sang Hun; Kim, Jae Hyun; Jang, Jyongsik; Park, Tai Hyun

2016-08-23

For several decades, significant efforts have been made in developing artificial taste sensors to recognize the five basic tastes. So far, the well-established taste sensor is an E-tongue, which is constructed with polymer and lipid membranes. However, the previous artificial taste sensors have limitations in various food, beverage, and cosmetic industries because of their failure to mimic human taste reception. There are many interactions between tastants. Therefore, detecting the interactions in a multiplexing system is required. Herein, we developed a duplex bioelectronic tongue (DBT) based on graphene field-effect transistors that were functionalized with heterodimeric human umami taste and sweet taste receptor nanovesicles. Two types of nanovesicles, which have human T1R1/T1R3 for the umami taste and human T1R2/T1R3 for the sweet taste on their membranes, immobilized on micropatterned graphene surfaces were used for the simultaneous detection of the umami and sweet tastants. The DBT platform led to highly sensitive and selective recognition of target tastants at low concentrations (ca. 100 nM). Moreover, our DBT was able to detect the enhancing effect of taste enhancers as in a human taste sensory system. This technique can be a useful tool for the detection of tastes instead of sensory evaluation and development of new artificial tastants in the food and beverage industry.

The surprisingly high human efficiency at learning to recognize faces

PubMed Central

Peterson, Matthew F.; Abbey, Craig K.; Eckstein, Miguel P.

2009-01-01

We investigated the ability of humans to optimize face recognition performance through rapid learning of individual relevant features. We created artificial faces with discriminating visual information heavily concentrated in single features (nose, eyes, chin or mouth). In each of 2500 learning blocks a feature was randomly selected and retained over the course of four trials, during which observers identified randomly sampled, noisy face images. Observers learned the discriminating feature through indirect feedback, leading to large performance gains. Performance was compared to a learning Bayesian ideal observer, resulting in unexpectedly high learning compared to previous studies with simpler stimuli. We explore various explanations and conclude that the higher learning measured with faces cannot be driven by adaptive eye movement strategies but can be mostly accounted for by suboptimalities in human face discrimination when observers are uncertain about the discriminating feature. We show that an initial bias of humans to use specific features to perform the task even though they are informed that each of four features is equally likely to be the discriminatory feature would lead to seemingly supra-optimal learning. We also examine the possibility of inefficient human integration of visual information across the spatially distributed facial features. Together, the results suggest that humans can show large performance improvement effects in discriminating faces as they learn to identify the feature containing the discriminatory information. PMID:19000918

Cross-cultural recognition of basic emotions through nonverbal emotional vocalizations

PubMed Central

Sauter, Disa A.; Eisner, Frank; Ekman, Paul; Scott, Sophie K.

2010-01-01

Emotional signals are crucial for sharing important information, with conspecifics, for example, to warn humans of danger. Humans use a range of different cues to communicate to others how they feel, including facial, vocal, and gestural signals. We examined the recognition of nonverbal emotional vocalizations, such as screams and laughs, across two dramatically different cultural groups. Western participants were compared to individuals from remote, culturally isolated Namibian villages. Vocalizations communicating the so-called “basic emotions” (anger, disgust, fear, joy, sadness, and surprise) were bidirectionally recognized. In contrast, a set of additional emotions was only recognized within, but not across, cultural boundaries. Our findings indicate that a number of primarily negative emotions have vocalizations that can be recognized across cultures, while most positive emotions are communicated with culture-specific signals. PMID:20133790

The discovery of the enteroviruses and the classification of poliovirus among them.

PubMed

Melnick, J L

1993-12-01

The history of the enteroviruses is described, and how poliovirus came to be recognized as the prototype species of the genus, a subdivision of the family Picornaviridae. Albert Sabin was one of the main contributors. He isolated several enterovirus types and established them as causative agents of human disease. The enteroviruses were discovered only after new methods were introduced for working with viruses. They are now recognized as constituting one of the genera of the picornavirus family. Pico-rna-virus stands for viruses which are small (pico), and have an RNA genome. The enterovirus genus includes the polioviruses, the coxsackieviruses and the echoviruses of humans, plus a number of enteroviruses of lower animals (e.g., monkeys, cattle, pigs, mice). Over 100 serotypes are now recognized, the first having been the polioviruses.

Anti-Semaphorin 3A neutralization monoclonal antibody prevents sepsis development in lipopolysaccharide-treated mice.

PubMed

Yamashita, Naoya; Jitsuki-Takahashi, Aoi; Ogawara, Miyuki; Ohkubo, Wataru; Araki, Tomomi; Hotta, Chie; Tamura, Tomohiko; Hashimoto, Shu-ichi; Yabuki, Takashi; Tsuji, Toru; Sasakura, Yukie; Okumura, Hiromi; Takaiwa, Aki; Koyama, Chika; Murakami, Koji; Goshima, Yoshio

2015-09-01

Semaphorin 3A (Sema3A), originally identified as a potent growth cone collapsing factor in developing sensory neurons, is now recognized as a key player in immune, cardiovascular, bone metabolism and neurological systems. Here we established an anti-Sema3A monoclonal antibody that neutralizes the effects of Sema3A both in vitro and in vivo. The anti-Sema3A neutralization chick IgM antibodies were screened by combining an autonomously diversifying library selection system and an in vitro growth cone collapse assay. We further developed function-blocking chick-mouse chimeric and humanized anti-Sema3A antibodies. We found that our anti-Sema3A antibodies were effective for improving the survival rate in lipopolysaccharide-induced sepsis in mice. Our antibody is a potential therapeutic agent that may prevent the onset of or alleviate symptoms of human diseases associated with Sema3A. © The Japanese Society for Immunology. 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Towards identification of an epilepsy gene in a large family with idiopathic generalized epilepsy

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

Roussear, M.; Lopes-Cendes, I.; Berkovic, S.F.

1994-09-01

To identify the disease gene in a large, multiplex family segregating an autosomal dominant form of idiopathic generalized epilepsy (IGE). The IGEs have been recognized for several decades as being genetically determined. However, large pedigrees with a clear Mendelian inheritance are not commonly available. This, and the presence of locus heterogeneity have been obstacles to the identification of linkage in several IGE syndromes. We have identified a large IGE kindred with fifty-eight living individuals, including 26 affecteds, showing a clear autosomal dominant inheritance with incomplete penetrance. Forty-fur informative individuals, including 23 affecteds, were selected for the linkage studies. We havemore » chosen 200 polymorphic microsatellite markers, about 20 cM apart, throughout the human autosomes as a genome-search linkage strategy. To date, 47 markers, representing 30% of the human genome, have been excluded for linkage in the Australian kindred. As our study progresses, we will report up-to-date results.« less

Current trends in small vocabulary speech recognition for equipment control

NASA Astrophysics Data System (ADS)

Doukas, Nikolaos; Bardis, Nikolaos G.

2017-09-01

Speech recognition systems allow human - machine communication to acquire an intuitive nature that approaches the simplicity of inter - human communication. Small vocabulary speech recognition is a subset of the overall speech recognition problem, where only a small number of words need to be recognized. Speaker independent small vocabulary recognition can find significant applications in field equipment used by military personnel. Such equipment may typically be controlled by a small number of commands that need to be given quickly and accurately, under conditions where delicate manual operations are difficult to achieve. This type of application could hence significantly benefit by the use of robust voice operated control components, as they would facilitate the interaction with their users and render it much more reliable in times of crisis. This paper presents current challenges involved in attaining efficient and robust small vocabulary speech recognition. These challenges concern feature selection, classification techniques, speaker diversity and noise effects. A state machine approach is presented that facilitates the voice guidance of different equipment in a variety of situations.

A recombinant dromedary antibody fragment (VHH or nanobody) directed against human Duffy antigen receptor for chemokines.

PubMed

Smolarek, Dorota; Hattab, Claude; Hassanzadeh-Ghassabeh, Gholamreza; Cochet, Sylvie; Gutiérrez, Carlos; de Brevern, Alexandre G; Udomsangpetch, Rachanee; Picot, Julien; Grodecka, Magdalena; Wasniowska, Kazimiera; Muyldermans, Serge; Colin, Yves; Le Van Kim, Caroline; Czerwinski, Marcin; Bertrand, Olivier

2010-10-01

Fy blood group antigens are carried by the Duffy antigen receptor for chemokines (DARC), a red cells receptor for Plasmodium vivax broadly implicated in human health and diseases. Recombinant VHHs, or nanobodies, the smallest intact antigen binding fragment derivative from the heavy chain-only antibodies present in camelids, were prepared from a dromedary immunized against DARC N-terminal extracellular domain and selected for DARC binding. A described VHH, CA52, does recognize native DARC on cells. It inhibits P. vivax invasion of erythrocytes and displaces interleukin-8 bound to DARC. The targeted epitope overlaps the well-defined DARC Fy6 epitope. K (D) of CA52-DARC equilibrium is sub-nanomolar, hence ideal to develop diagnostic or therapeutic compounds. Immunocapture by immobilized CA52 yielded highly purified DARC from engineered K562 cells. This first report on a VHH with specificity for a red blood cell protein exemplifies VHHs' potentialities to target, to purify, and to modulate the function of cellular markers.

Oncogene-like induction of cellular invasion from centrosome amplification

PubMed Central

Godinho, Susana A.; Picone, Remigio; Burute, Mithila; Dagher, Regina; Su, Ying; Leung, Cheuk T.; Polyak, Kornelia; Brugge, Joan S.; Thery, Manuel; Pellman, David

2014-01-01

Centrosome amplification has long been recognized as a feature of human tumors, however its role in tumorigenesis remains unclear1. Centrosome amplification is poorly tolerated by non-transformed cells, and, in the absence of selection, extra centrosomes are spontaneously lost2. Thus, the high frequency of centrosome amplification, particularly in more aggressive tumors3, raises the possibility that extra centrosomes could, in some contexts, confer advantageous characteristics that promote tumor progression. Using a three-dimensional model system and other approaches to culture human mammary epithelial cells, we find that centrosome amplification triggers cell invasion. This invasive behavior is similar to that induced by overexpression of the breast cancer oncogene ErbB24 and indeed enhances invasiveness triggered by ErbB2. We show that, through increased centrosomal microtubule nucleation, centrosome amplification increases Rac1 activity, which disrupts normal cell-cell adhesion and promotes invasion. These findings demonstrate that centrosome amplification, a structural alteration of the cytoskeleton, can promote features of malignant transformation. PMID:24739973

Carbohydrate Microarrays Identify Blood Group Precursor Cryptic Epitopes as Potential Immunological Targets of Breast Cancer

PubMed Central

Wang, Denong; Tang, Jin; Liu, Shaoyi

2015-01-01

Using carbohydrate microarrays, we explored potential natural ligands of antitumor monoclonal antibody HAE3. This antibody was raised against a murine mammary tumor antigen but was found to cross-react with a number of human epithelial tumors in tissues. Our carbohydrate microarray analysis reveals that HAE3 is specific for an O-glycan cryptic epitope that is normally hidden in the cores of blood group substances. Using HAE3 to screen tumor cell surface markers by flow cytometry, we found that the HAE3 glycoepitope, gpHAE3, was highly expressed by a number of human breast cancer cell lines, including some triple-negative cancers that lack the estrogen, progesterone, and Her2/neu receptors. Taken together, we demonstrate that HAE3 recognizes a conserved cryptic glycoepitope of blood group precursors, which is nevertheless selectively expressed and surface-exposed in certain breast tumor cells. The potential of this class of O-glycan cryptic antigens in breast cancer subtyping and targeted immunotherapy warrants further investigation. PMID:26539555

A computationally designed inhibitor of an Epstein-Barr viral Bcl-2 protein induces apoptosis in infected cells

PubMed Central

Shen, Betty W.; Song, Yifan; Frayo, Shani; Convertine, Anthony J.; Margineantu, Daciana; Booth, Garrett; Correia, Bruno E.; Cheng, Yuanhua; Schief, William R.; Hockenbery, David M.; Press, Oliver W.; Stoddard, Barry L.; Stayton, Patrick S.; Baker, David

2014-01-01

SUMMARY Since apoptosis of infected cells can limit virus production and spread, some viruses have co-opted prosurvival genes from the host. This includes the Epstein-Barr virus (EBV) gene BHRF1, a homologue of human Bcl-2 proteins that block apoptosis and are associated with cancer. Computational design and experimental optimization were used to generate a novel protein called BINDI that binds BHRF1 with picomolar affinity. BINDI recognizes the hydrophobic cleft of BHRF1 in a manner similar to other Bcl-2 protein interactions, but makes many additional contacts to achieve exceptional affinity and specificity. BINDI induces apoptosis in EBV-infected cancer lines, and when delivered with an antibody-targeted intracellular delivery carrier, BINDI suppressed tumor growth and extended survival in a xenograft disease model of EBV-positive human lymphoma. High specificity designed proteins that selectively kill target cells may provide an advantage over the toxic compounds used in current generation antibody-drug conjugates. PMID:24949974

77 FR 70163 - Recognition of Entities for the Accreditation of Qualified Health Plans

Federal Register 2010, 2011, 2012, 2013, 2014

2012-11-23

... DEPARTMENT OF HEALTH AND HUMAN SERVICES [CMS-9961-N] Recognition of Entities for the Accreditation... as recognized accrediting entities for the purposes of fulfilling the accreditation requirement as... a recognized accrediting entity on a uniform timeline established by the applicable Exchange. On...

21 CFR 182.8252 - Choline chloride.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 3 2012-04-01 2012-04-01 false Choline chloride. 182.8252 Section 182.8252 Food... HUMAN CONSUMPTION (CONTINUED) SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients § 182.8252 Choline chloride. (a) Product. Choline chloride. (b) Conditions of use. This substance is generally recognized as...

21 CFR 182.8252 - Choline chloride.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 3 2013-04-01 2013-04-01 false Choline chloride. 182.8252 Section 182.8252 Food... HUMAN CONSUMPTION (CONTINUED) SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients § 182.8252 Choline chloride. (a) Product. Choline chloride. (b) Conditions of use. This substance is generally recognized as...

21 CFR 182.8250 - Choline bitartrate.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 3 2013-04-01 2013-04-01 false Choline bitartrate. 182.8250 Section 182.8250 Food... HUMAN CONSUMPTION (CONTINUED) SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients § 182.8250 Choline bitartrate. (a) Product. Choline bitartrate. (b) Conditions of use. This substance is generally recognized as...

21 CFR 182.8250 - Choline bitartrate.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Choline bitartrate. 182.8250 Section 182.8250 Food... HUMAN CONSUMPTION (CONTINUED) SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients § 182.8250 Choline bitartrate. (a) Product. Choline bitartrate. (b) Conditions of use. This substance is generally recognized as...

21 CFR 182.8252 - Choline chloride.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Choline chloride. 182.8252 Section 182.8252 Food... HUMAN CONSUMPTION (CONTINUED) SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients § 182.8252 Choline chloride. (a) Product. Choline chloride. (b) Conditions of use. This substance is generally recognized as...

21 CFR 182.8250 - Choline bitartrate.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Choline bitartrate. 182.8250 Section 182.8250 Food... HUMAN CONSUMPTION (CONTINUED) SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients § 182.8250 Choline bitartrate. (a) Product. Choline bitartrate. (b) Conditions of use. This substance is generally recognized as...

21 CFR 182.8250 - Choline bitartrate.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 3 2012-04-01 2012-04-01 false Choline bitartrate. 182.8250 Section 182.8250 Food... HUMAN CONSUMPTION (CONTINUED) SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients § 182.8250 Choline bitartrate. (a) Product. Choline bitartrate. (b) Conditions of use. This substance is generally recognized as...

21 CFR 182.6197 - Calcium diacetate.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Calcium diacetate. 182.6197 Section 182.6197 Food... HUMAN CONSUMPTION (CONTINUED) SUBSTANCES GENERALLY RECOGNIZED AS SAFE Sequestrants 1 § 182.6197 Calcium diacetate. (a) Product. Calcium diacetate. (b) Conditions of use. This substance is generally recognized as...

21 CFR 182.6197 - Calcium diacetate.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Calcium diacetate. 182.6197 Section 182.6197 Food... HUMAN CONSUMPTION (CONTINUED) SUBSTANCES GENERALLY RECOGNIZED AS SAFE Sequestrants 1 § 182.6197 Calcium diacetate. (a) Product. Calcium diacetate. (b) Conditions of use. This substance is generally recognized as...

21 CFR 182.6757 - Sodium gluconate.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Sodium gluconate. 182.6757 Section 182.6757 Food... HUMAN CONSUMPTION (CONTINUED) SUBSTANCES GENERALLY RECOGNIZED AS SAFE Sequestrants 1 § 182.6757 Sodium gluconate. (a) Product. Sodium gluconate. (b) Conditions of use. This substance is generally recognized as...

21 CFR 182.6757 - Sodium gluconate.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 3 2013-04-01 2013-04-01 false Sodium gluconate. 182.6757 Section 182.6757 Food... HUMAN CONSUMPTION (CONTINUED) SUBSTANCES GENERALLY RECOGNIZED AS SAFE Sequestrants 1 § 182.6757 Sodium gluconate. (a) Product. Sodium gluconate. (b) Conditions of use. This substance is generally recognized as...

21 CFR 182.6757 - Sodium gluconate.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 3 2012-04-01 2012-04-01 false Sodium gluconate. 182.6757 Section 182.6757 Food... HUMAN CONSUMPTION (CONTINUED) SUBSTANCES GENERALLY RECOGNIZED AS SAFE Sequestrants 1 § 182.6757 Sodium gluconate. (a) Product. Sodium gluconate. (b) Conditions of use. This substance is generally recognized as...

21 CFR 182.6757 - Sodium gluconate.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Sodium gluconate. 182.6757 Section 182.6757 Food... HUMAN CONSUMPTION (CONTINUED) SUBSTANCES GENERALLY RECOGNIZED AS SAFE Sequestrants 1 § 182.6757 Sodium gluconate. (a) Product. Sodium gluconate. (b) Conditions of use. This substance is generally recognized as...

21 CFR 182.6197 - Calcium diacetate.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 3 2012-04-01 2012-04-01 false Calcium diacetate. 182.6197 Section 182.6197 Food... HUMAN CONSUMPTION (CONTINUED) SUBSTANCES GENERALLY RECOGNIZED AS SAFE Sequestrants 1 § 182.6197 Calcium diacetate. (a) Product. Calcium diacetate. (b) Conditions of use. This substance is generally recognized as...

21 CFR 182.6197 - Calcium diacetate.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 3 2013-04-01 2013-04-01 false Calcium diacetate. 182.6197 Section 182.6197 Food... HUMAN CONSUMPTION (CONTINUED) SUBSTANCES GENERALLY RECOGNIZED AS SAFE Sequestrants 1 § 182.6197 Calcium diacetate. (a) Product. Calcium diacetate. (b) Conditions of use. This substance is generally recognized as...

Consciousness Counseling: New Roles and New Goals.

ERIC Educational Resources Information Center

Roberts, Thomas Bradford

1979-01-01

Presents a systematic attempt to help counselors operate within the areas of transcendence and states of consciousness. Consciousness counseling recognizes that human experience includes the person and that it also goes beyond the self to include transpersonal experiences. Consciousness counseling recognizes that people experience many states of…

Drug Dependence and Abuse: A Selected Bibliography.

ERIC Educational Resources Information Center

National Inst. on Drug Abuse (DHEW/PHS), Rockville, MD. National Clearinghouse for Drug Abuse Information.

This selected list of references is designed to provide an introduction to both scientific and popular drug abuse literature. Criteria for selection are presented and include: (1) 1969 or 1970 books by recognized and authoritative writers, (2) current and responsible research, (3) classic books, articles and studies, and (4) factual popular…

TRIM-directed selective autophagy regulates immune activation.

PubMed

Kimura, Tomonori; Jain, Ashish; Choi, Seong Won; Mandell, Michael A; Johansen, Terje; Deretic, Vojo

2017-05-04

Selectivity of autophagy is achieved by target recognition; however, the number of autophagy receptors identified so far is limited. In this study we demonstrate that a subset of tripartite motif (TRIM) proteins mediate selective autophagy of key regulators of inflammatory signaling. MEFV/TRIM20, and TRIM21 act as autophagic receptors recognizing their cognate targets and delivering them for autophagic degradation. MEFV recognizes the inflammasome components NLRP3, CASP1 and NLRP1, whereas TRIM21 specifically recognizes the activated, dimeric from of IRF3 inducing type I interferon gene expression. MEFV and TRIM21 have a second activity, whereby they act not only as receptors but also recruit and organize key components of autophagic machinery consisting of ULK1, BECN1, ATG16L1, and mammalian homologs of Atg8, with a preference for GABARAP. MEFV capacity to organize the autophagy apparatus is affected by common mutations causing familial Mediterranean fever. These findings reveal a general mode of action of TRIMs as autophagic receptor-regulators performing a highly-selective type of autophagy (precision autophagy), with MEFV specializing in the suppression of inflammasome and CASP1 activation engendering IL1B/interleukin-1β production and implicated in the form of cell death termed pyroptosis, whereas TRIM21 dampens type I interferon responses.

The past, present, and future of soils and human health studies

NASA Astrophysics Data System (ADS)

Brevik, E. C.; Sauer, T. J.

2015-01-01

The idea that human health is tied to the soil is not a new one. As far back as circa 1400 BC the Bible depicts Moses as understanding that fertile soil was essential to the well-being of his people. In 400 BC the Greek philosopher Hippocrates provided a list of things that should be considered in a proper medical evaluation, including the properties of the local ground. By the late 1700s and early 1800s, American farmers had recognized that soil properties had some connection to human health. In the modern world, we recognize that soils have a distinct influence on human health. We recognize that soils influence (1) food availability and quality (food security), (2) human contact with various chemicals, and (3) human contact with various pathogens. Soils and human health studies include investigations into nutrient supply through the food chain and routes of exposure to chemicals and pathogens. However, making strong, scientific connections between soils and human health can be difficult. There are multiple variables to consider in the soil environment, meaning traditional scientific studies that seek to isolate and manipulate a single variable often do not provide meaningful data. The complete study of soils and human health also involves many different specialties such as soil scientists, toxicologists, medical professionals, anthropologists, etc. These groups do not traditionally work together on research projects, and do not always effectively communicate with one another. Climate change and how it will affect the soil environment/ecosystem going into the future is another variable affecting the relationship between soils and health. Future successes in soils and human health research will require effectively addressing difficult issues such as these.

The Human Side of Library Automation.

ERIC Educational Resources Information Center

Morris, Anne; Barnacle, Stephen

1989-01-01

Discusses the importance of recognizing the human component in library automation systems to ensure the smooth and efficient operation of the system. Human factors considerations are discussed in terms of health and safety aspects, ergonomics, workplace design, and job organization. (41 references) (CLB)

The ER stress sensor PERK luminal domain functions as a molecular chaperone to interact with misfolded proteins

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

Wang, Peng; Li, Jingzhi; Sha, Bingdong

2016-11-29

PERK is one of the major sensor proteins which can detect the protein-folding imbalance generated by endoplasmic reticulum (ER) stress. It remains unclear how the sensor protein PERK is activated by ER stress. It has been demonstrated that the PERK luminal domain can recognize and selectively interact with misfolded proteins but not native proteins. Moreover, the PERK luminal domain may function as a molecular chaperone to directly bind to and suppress the aggregation of a number of misfolded model proteins. The data strongly support the hypothesis that the PERK luminal domain can interact directly with misfolded proteins to induce ERmore » stress signaling. To illustrate the mechanism by which the PERK luminal domain interacts with misfolded proteins, the crystal structure of the human PERK luminal domain was determined to 3.2 Å resolution. Two dimers of the PERK luminal domain constitute a tetramer in the asymmetric unit. Superimposition of the PERK luminal domain molecules indicated that the β-sandwich domain could adopt multiple conformations. It is hypothesized that the PERK luminal domain may utilize its flexible β-sandwich domain to recognize and interact with a broad range of misfolded proteins.« less

The ER stress sensor PERK luminal domain functions as a molecular chaperone to interact with misfolded proteins.

PubMed

Wang, Peng; Li, Jingzhi; Sha, Bingdong

2016-12-01

PERK is one of the major sensor proteins which can detect the protein-folding imbalance generated by endoplasmic reticulum (ER) stress. It remains unclear how the sensor protein PERK is activated by ER stress. It has been demonstrated that the PERK luminal domain can recognize and selectively interact with misfolded proteins but not native proteins. Moreover, the PERK luminal domain may function as a molecular chaperone to directly bind to and suppress the aggregation of a number of misfolded model proteins. The data strongly support the hypothesis that the PERK luminal domain can interact directly with misfolded proteins to induce ER stress signaling. To illustrate the mechanism by which the PERK luminal domain interacts with misfolded proteins, the crystal structure of the human PERK luminal domain was determined to 3.2 Å resolution. Two dimers of the PERK luminal domain constitute a tetramer in the asymmetric unit. Superimposition of the PERK luminal domain molecules indicated that the β-sandwich domain could adopt multiple conformations. It is hypothesized that the PERK luminal domain may utilize its flexible β-sandwich domain to recognize and interact with a broad range of misfolded proteins.

Survivors Remorse: antibody-mediated protection against HIV-1.

PubMed

Lewis, George K; Pazgier, Marzena; DeVico, Anthony L

2017-01-01

It is clear that antibodies can play a pivotal role in preventing the transmission of HIV-1 and large efforts to identify an effective antibody-based vaccine to quell the epidemic. Shortly after HIV-1 was discovered as the cause of AIDS, the search for epitopes recognized by neutralizing antibodies became the driving strategy for an antibody-based vaccine. Neutralization escape variants were discovered shortly thereafter, and, after almost three decades of investigation, it is now known that autologous neutralizing antibody responses and their selection of neutralization resistant HIV-1 variants can lead to broadly neutralizing antibodies in some infected individuals. This observation drives an intensive effort to identify a vaccine to elicit broadly neutralizing antibodies. In contrast, there has been less systematic study of antibody specificities that must rely mainly or exclusively on other protective mechanisms, although non-human primate (NHP) studies as well as the RV144 vaccine trial indicate that non-neutralizing antibodies can contribute to protection. Here we propose a novel strategy to identify new epitope targets recognized by these antibodies for which viral escape is unlikely or impossible. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Recognizing human activities using appearance metric feature and kinematics feature

NASA Astrophysics Data System (ADS)

Qian, Huimin; Zhou, Jun; Lu, Xinbiao; Wu, Xinye

2017-05-01

The problem of automatically recognizing human activities from videos through the fusion of the two most important cues, appearance metric feature and kinematics feature, is considered. And a system of two-dimensional (2-D) Poisson equations is introduced to extract the more discriminative appearance metric feature. Specifically, the moving human blobs are first detected out from the video by background subtraction technique to form a binary image sequence, from which the appearance feature designated as the motion accumulation image and the kinematics feature termed as centroid instantaneous velocity are extracted. Second, 2-D discrete Poisson equations are employed to reinterpret the motion accumulation image to produce a more differentiated Poisson silhouette image, from which the appearance feature vector is created through the dimension reduction technique called bidirectional 2-D principal component analysis, considering the balance between classification accuracy and time consumption. Finally, a cascaded classifier based on the nearest neighbor classifier and two directed acyclic graph support vector machine classifiers, integrated with the fusion of the appearance feature vector and centroid instantaneous velocity vector, is applied to recognize the human activities. Experimental results on the open databases and a homemade one confirm the recognition performance of the proposed algorithm.

Molecular mechanisms of retroviral integration site selection

PubMed Central

Kvaratskhelia, Mamuka; Sharma, Amit; Larue, Ross C.; Serrao, Erik; Engelman, Alan

2014-01-01

Retroviral replication proceeds through an obligate integrated DNA provirus, making retroviral vectors attractive vehicles for human gene-therapy. Though most of the host cell genome is available for integration, the process of integration site selection is not random. Retroviruses differ in their choice of chromatin-associated features and also prefer particular nucleotide sequences at the point of insertion. Lentiviruses including HIV-1 preferentially integrate within the bodies of active genes, whereas the prototypical gammaretrovirus Moloney murine leukemia virus (MoMLV) favors strong enhancers and active gene promoter regions. Integration is catalyzed by the viral integrase protein, and recent research has demonstrated that HIV-1 and MoMLV targeting preferences are in large part guided by integrase-interacting host factors (LEDGF/p75 for HIV-1 and BET proteins for MoMLV) that tether viral intasomes to chromatin. In each case, the selectivity of epigenetic marks on histones recognized by the protein tether helps to determine the integration distribution. In contrast, nucleotide preferences at integration sites seem to be governed by the ability for the integrase protein to locally bend the DNA duplex for pairwise insertion of the viral DNA ends. We discuss approaches to alter integration site selection that could potentially improve the safety of retroviral vectors in the clinic. PMID:25147212

The role of selective estrogen receptor modulators in the treatment of schizophrenia.

PubMed

Bratek, Agnieszka; Krysta, Krzysztof; Drzyzga, Karolina; Barańska, Justyna; Kucia, Krzysztof

2016-09-01

Gender differences in schizophrenia have been recognized for a long time and it has been widely accepted that sex steroid hormones, especially estradiol, are strongly attributed to this fact. Two hypotheses regarding estradiol action in psychoses gained special research attention - the estrogen protection hypothesis and hypoestrogenism hypothesis. A growing number of studies have shown benefits in augmenting antipsychotic treatment with estrogens or selective estrogen receptor modulators (SERM). This review is focused on the role of selective estrogen receptor modulators in the treatment of schizophrenic patients. In order to achieve this result PubMed was searched using the following terms: schizophrenia, raloxifene, humans. We reviewed only randomized, placebo-controlled studies. Raloxifene, a selective estrogen receptor modulator was identified as useful to improve negative, positive, and general psychopathological symptoms, and also cognitive functions. All reviewed studies indicated improvement in at least one studied domain. Augmentation with raloxifene was found to be a beneficial treatment strategy for chronic schizophrenia both in female and male patients, however potential side effects (a small increase in the risk of venous thromboembolism and endometrial cancer) should be carefully considered. SERMs could be an effective augmentation strategy in the treatment of both men women with schizophrenia, although further research efforts are needed to study potential long-term side effects.

Obligate multivalent recognition of cell surface tomoregulin following selection from a multivalent phage antibody library.

PubMed

Heitner, Tara; Satozawa, Noboru; McLean, Kirk; Vogel, David; Cobb, Ronald R; Liu, Bing; Mahmoudi, Mithra; Finster, Silke; Larsen, Brent; Zhu, Ying; Zhou, Hongxing; Müller-Tiemann, Beate; Monteclaro, Felipe; Zhao, Xiao-Yan; Light, David R

2006-12-01

A therapeutic antibody candidate (AT-19) isolated using multivalent phage display binds native tomoregulin (TR) as a mul-timer not as a monomer. This report raises the importance of screening and selecting phage antibodies on native antigen and reemphasizes the possibility that potentially valuable antibodies are discarded when a monomeric phage display system is used for screening. A detailed live cell panning selection and screening method to isolate multivalently active antibodies is described. AT-19 is a fully human antibody recognizing the cell surface protein TR, a proposed prostate cancer target for therapeutic antibody internalization. AT-19 was isolated from a multivalent single-chain variable fragment (scFv) antibody library rescued with hyperphage. The required multivalency for isolation of AT-19 is supported by fluorescence activated cell sorting data demonstrating binding of the multivalent AT-19 phage particles at high phage concentrations and failure of monovalent particles to bind. Pure monomeric scFv AT-19 does not bind native receptor on cells, whereas dimeric scFv or immunoglobulin G binds with nanomolar affinity. The isolation of AT-19 antibody with obligate bivalent binding activity to native TR is attributed to the use of a multivalent display of scFv on phage and the method for selecting and screening by alternate use of 2 recombinant cell lines.

Easy Ergonomics: A Guide to Selecting Non-Powered Hand Tools

MedlinePlus

... identifying the presence or absence of basic ergonomic design features (Dababneh et al.*). The right tool will ... Cal/OSHA). Both agencies recognize the importance of design and selection of hand tools in strategies to ...

Ethics in medical technologies: the Roman Catholic viewpoint.

PubMed

Zyciński, Joseph

2006-06-01

New medical techniques and novel scientific discoveries bring many basic questions concerning the role of human dignity in medical research as well as in the society of the future. This paper presents the Roman Catholic approach to the use of new technologies, the research of human embryos, the ethical aspects of studies on the human genome. The concept of "human ecology", as proposed by John Paul II, is introduced to reconcile the academic freedom of research with insurmountable ethical barriers which must be recognized to defend human dignity. In critical appraisal of Peter Singer's concept of the quality of life the author points out that it is irrational to try to reduce this quality to the level of biological parameters. Human dignity as well as the sanctity of life express also a quality of life so important for the cultural growth of Homo sapiens. To protect human ecology it is our moral duty to defend human dignity and to recognize the importance of those values that are fundamental in the process of development of the human species.

Great Apes' Capacities to Recognize Relational Similarity

ERIC Educational Resources Information Center

Haun, Daniel B. M.; Call, Josep

2009-01-01

Recognizing relational similarity relies on the ability to understand that defining object properties might not lie in the objects individually, but in the relations of the properties of various object to each other. This aptitude is highly relevant for many important human skills such as language, reasoning, categorization and understanding…

Comparison of printed glycan array, suspension array and ELISA in the detection of human anti-glycan antibodies.

PubMed

Pochechueva, Tatiana; Jacob, Francis; Goldstein, Darlene R; Huflejt, Margaret E; Chinarev, Alexander; Caduff, Rosemarie; Fink, Daniel; Hacker, Neville; Bovin, Nicolai V; Heinzelmann-Schwarz, Viola

2011-12-01

Anti-glycan antibodies represent a vast and yet insufficiently investigated subpopulation of naturally occurring and adaptive antibodies in humans. Recently, a variety of glycan-based microarrays emerged, allowing high-throughput profiling of a large repertoire of antibodies. As there are no direct approaches for comparison and evaluation of multi-glycan assays we compared three glycan-based immunoassays, namely printed glycan array (PGA), fluorescent microsphere-based suspension array (SA) and ELISA for their efficacy and selectivity in profiling anti-glycan antibodies in a cohort of 48 patients with and without ovarian cancer. The ABO blood group glycan antigens were selected as well recognized ligands for sensitivity and specificity assessments. As another ligand we selected P(1), a member of the P blood group system recently identified by PGA as a potential ovarian cancer biomarker. All three glyco-immunoassays reflected the known ABO blood groups with high performance. In contrast, anti-P(1) antibody binding profiles displayed much lower concordance. Whilst anti-P(1) antibody levels between benign controls and ovarian cancer patients were significantly discriminated using PGA (p=0.004), we got only similar results using SA (p=0.03) but not for ELISA. Our findings demonstrate that whilst assays were largely positively correlated, each presents unique characteristic features and should be validated by an independent patient cohort rather than another array technique. The variety between methods presumably reflects the differences in glycan presentation and the antigen/antibody ratio, assay conditions and detection technique. This indicates that the glycan-antibody interaction of interest has to guide the assay selection. © The Author(s) 2011. This article is published with open access at Springerlink.com

Antibodies against Escherichia coli O24 and O56 O-Specific Polysaccharides Recognize Epitopes in Human Glandular Epithelium and Nervous Tissue

PubMed Central

Korzeniowska-Kowal, Agnieszka; Kochman, Agata; Gamian, Elżbieta; Lis-Nawara, Anna; Lipiński, Tomasz; Seweryn, Ewa; Ziółkowski, Piotr; Gamian, Andrzej

2015-01-01

Lipopolysaccharide (LPS), the major component of the outer membrane of Gram-negative bacteria, contains the O-polysaccharide, which is important to classify bacteria into different O-serological types within species. The O-polysaccharides of serotypes O24 and O56 of E. coli contain sialic acid in their structures, already established in our previous studies. Here, we report the isolation of specific antibodies with affinity chromatography using immobilized lipopolysaccharides. Next, we evaluated the reactivity of anti-O24 and anti-O56 antibody on human tissues histologically. The study was conducted under the assumption that the sialic acid based molecular identity of bacterial and tissue structures provides not only an understanding of the mimicry-based bacterial pathogenicity. Cross-reacting antibodies could be used to recognize specific human tissues depending on their histogenesis and differentiation, which might be useful for diagnostic purposes. The results indicate that various human tissues are recognized by anti-O24 and anti-O56 antibodies. Interestingly, only a single specific reactivity could be found in the anti-O56 antibody preparation. Several tissues studied were not reactive with either antibody, thus proving that the presence of cross-reactive antigens was tissue specific. In general, O56 antibody performed better than O24 in staining epithelial and nervous tissues. Positive staining was observed for both normal (ganglia) and tumor tissue (ganglioneuroma). Epithelial tissue showed positive staining, but an epitope recognized by O56 antibody should be considered as a marker of glandular epithelium. The reason is that malignant glandular tumor and its metastasis are stained, and also epithelium of renal tubules and glandular structures of the thyroid gland are stained. Stratified epithelium such as that of skin is definitely not stained. Therefore, the most relevant observation is that the epitope recognized by anti-O56 antibodies is a new marker specific for glandular epithelium and nervous tissue. Further studies should be performed to determine the structure of the tissue epitope recognized. PMID:26086646

Octopuses (Enteroctopus dofleini) recognize individual humans.

PubMed

Anderson, Roland C; Mather, Jennifer A; Monette, Mathieu Q; Zimsen, Stephanie R M

2010-01-01

This study exposed 8 Enteroctopus dofleini separately to 2 unfamiliar individual humans over a 2-week period under differing circumstances. One person consistently fed the octopuses and the other touched them with a bristly stick. Each human recorded octopus body patterns, behaviors, and respiration rates directly after each treatment. At the end of 2 weeks, a body pattern (a dark Eyebar) and 2 behaviors (reaching arms toward or away from the tester and funnel direction) were significantly different in response to the 2 humans. The respiration rate of the 4 larger octopuses changed significantly in response to the 2 treatments; however, there was no significant difference in the 4 smaller octopuses' respiration. Octopuses' ability to recognize humans enlarges our knowledge of the perceptual ability of this nonhuman animal, which depends heavily on learning in response to visual information. Any training paradigm should take such individual recognition into consideration as it could significantly alter the octopuses' responses.

Genotype by environment interaction and breeding for robustness in livestock

PubMed Central

Rauw, Wendy M.; Gomez-Raya, Luis

2015-01-01

The increasing size of the human population is projected to result in an increase in meat consumption. However, at the same time, the dominant position of meat as the center of meals is on the decline. Modern objections to the consumption of meat include public concerns with animal welfare in livestock production systems. Animal breeding practices have become part of the debate since it became recognized that animals in a population that have been selected for high production efficiency are more at risk for behavioral, physiological and immunological problems. As a solution, animal breeding practices need to include selection for robustness traits, which can be implemented through the use of reaction norms analysis, or though the direct inclusion of robustness traits in the breeding objective and in the selection index. This review gives an overview of genotype × environment interactions (the influence of the environment, reaction norms, phenotypic plasticity, canalization, and genetic homeostasis), reaction norms analysis in livestock production, options for selection for increased levels of production and against environmental sensitivity, and direct inclusion of robustness traits in the selection index. Ethical considerations of breeding for improved animal welfare are discussed. The discussion on animal breeding practices has been initiated and is very alive today. This positive trend is part of the sustainable food production movement that aims at feeding 9.15 billion people not just in the near future but also beyond. PMID:26539207

Elongation as a factor in artefacts of humans and other animals: an Acheulean example in comparative context.

PubMed

Gowlett, J A J

2013-11-19

Elongation is a commonly found feature in artefacts made and used by humans and other animals and can be analysed in comparative study. Whether made for use in hand or beak, the artefacts have some common properties of length, breadth, thickness and balance point, and elongation can be studied as a factor relating to construction or use of a long axis. In human artefacts, elongation can be traced through the archaeological record, for example in stone blades of the Upper Palaeolithic (traditionally regarded as more sophisticated than earlier artefacts), and in earlier blades of the Middle Palaeolithic. It is now recognized that elongation extends to earlier Palaeolithic artefacts, being found in the repertoire of both Neanderthals and more archaic humans. Artefacts used by non-human animals, including chimpanzees, capuchin monkeys and New Caledonian crows show selection for diameter and length, and consistent interventions of modification. Both chimpanzees and capuchins trim side branches from stems, and appropriate lengths of stave are selected or cut. In human artefacts, occasional organic finds show elongation back to about 0.5 million years. A record of elongation achieved in stone tools survives to at least 1.75 Ma (million years ago) in the Acheulean tradition. Throughout this tradition, some Acheulean handaxes are highly elongated, usually found with others that are less elongated. Finds from the million-year-old site of Kilombe and Kenya are given as an example. These findings argue that the elongation need not be integral to a design, but that artefacts may be the outcome of adjustments to individual variables. Such individual adjustments are seen in animal artefacts. In the case of a handaxe, the maker must balance the adjustments to achieve a satisfactory outcome in the artefact as a whole. It is argued that the need to make decisions about individual variables within multivariate objects provides an essential continuity across artefacts made by different species.

NREL: News - Scientific American' Recognizes Solar Cell Research

Science.gov Websites

Scientific American' Recognizes Solar Cell Research Monday November 11, 2002 Magazine Names NREL to . NREL's research into multi-junction solar cells for more than a decade has led the way to ever more photovoltaic research can be found at www.nrel.gov/ncpv/. Selected by the magazine's Board of Editors, the

Ghost-in-the-Machine reveals human social signals for human–robot interaction

PubMed Central

Loth, Sebastian; Jettka, Katharina; Giuliani, Manuel; de Ruiter, Jan P.

2015-01-01

We used a new method called “Ghost-in-the-Machine” (GiM) to investigate social interactions with a robotic bartender taking orders for drinks and serving them. Using the GiM paradigm allowed us to identify how human participants recognize the intentions of customers on the basis of the output of the robotic recognizers. Specifically, we measured which recognizer modalities (e.g., speech, the distance to the bar) were relevant at different stages of the interaction. This provided insights into human social behavior necessary for the development of socially competent robots. When initiating the drink-order interaction, the most important recognizers were those based on computer vision. When drink orders were being placed, however, the most important information source was the speech recognition. Interestingly, the participants used only a subset of the available information, focussing only on a few relevant recognizers while ignoring others. This reduced the risk of acting on erroneous sensor data and enabled them to complete service interactions more swiftly than a robot using all available sensor data. We also investigated socially appropriate response strategies. In their responses, the participants preferred to use the same modality as the customer’s requests, e.g., they tended to respond verbally to verbal requests. Also, they added redundancy to their responses, for instance by using echo questions. We argue that incorporating the social strategies discovered with the GiM paradigm in multimodal grammars of human–robot interactions improves the robustness and the ease-of-use of these interactions, and therefore provides a smoother user experience. PMID:26582998

How can we tackle energy efficiency in IoT based smart buildings?

PubMed

Moreno, M Victoria; Úbeda, Benito; Skarmeta, Antonio F; Zamora, Miguel A

2014-05-30

Nowadays, buildings are increasingly expected to meet higher and more complex performance requirements. Among these requirements, energy efficiency is recognized as an international goal to promote energy sustainability of the planet. Different approaches have been adopted to address this goal, the most recent relating consumption patterns with human occupancy. In this work, we analyze what are the main parameters that should be considered to be included in any building energy management. The goal of this analysis is to help designers to select the most relevant parameters to control the energy consumption of buildings according to their context, selecting them as input data of the management system. Following this approach, we select three reference smart buildings with different contexts, and where our automation platform for energy monitoring is deployed. We carry out some experiments in these buildings to demonstrate the influence of the parameters identified as relevant in the energy consumption of the buildings. Then, in two of these buildings are applied different control strategies to save electrical energy. We describe the experiments performed and analyze the results. The first stages of this evaluation have already resulted in energy savings of about 23% in a real scenario.

α-Amino Acid Derived Benzimidazole-Linked Rhodamines: A Case of Substitution Effect at the Amino Acid Site toward Spiro Ring Opening for Selective Sensing of Al3+ Ions.

PubMed

Majumdar, Anupam; Mondal, Subhendu; Daniliuc, Constantin G; Sahu, Debashis; Ganguly, Bishwajit; Ghosh, Sourav; Ghosh, Utpal; Ghosh, Kumaresh

2017-08-07

α-Amino acid derived benzimidazole-linked rhodamines have been synthesized, and their metal ion sensing properties have been evaluated. Experimentally, l-valine- and l-phenylglycine-derived benzimidazole-based rhodamines 1 and 2 selectively recognize Al 3+ ion in aqueous CH 3 CN (CH 3 CN/H 2 O 4/1 v/v, 10 mM tris HCl buffer, pH 7.0) over the other cations by exhibiting color and "turn-on" emission changes. In contrast, glycine-derived benzimidazole 3 remains silent in the recognition event and emphasizes the role of α-substitution of amino acid undertaken in the design. The fact has been addressed on the basis of the single-crystal X-ray structures and theoretical calculations. Moreover, pink 1·Al 3+ and 2·Al 3+ ensembles selectively sensed F - ions over other halides through a discharge of color. Importantly, compounds 1 and 2 are cell permeable and have been used as imaging reagents for the detection of Al 3+ uptake in human lung carcinoma cell line A549.

Applying a feminist analysis model to selected nursing studies of women with HIV.

PubMed

Bunting, S M

1997-01-01

Women's mental health has been linked to oppression and to oppressive practices in health care. Feminist approaches to health care delivery and research have been suggested as a remedy for the subtle and overt oppression faced by women, and many nurses have used feminist principles to conduct and report their research and to critique existing studies. Though nursing authors have identified useful feminist guides for conducting and reporting research, few examples of the practice of feminist critiques of research are available in the nursing literature. This analysis synthesizes and adapts feminist principles from nursing literature and presents a feminist model to review selected nursing research reports of women with human immunodeficiency virus (HIV). A convenience sample of eight articles from nursing journals was examined for statements or implications that the author(s) (a) perceived the purposes of the study as benefiting women, (b) demonstrated an awareness of the structures and policies that oppress women, (c) were sensitive to issues of diversity, (d) were committed to social change, and (e) recognized the female participants' strengths. The selected articles were found to meet many of the feminist criteria, although these principles were not always explicitly addressed in the articles.

How can We Tackle Energy Efficiency in IoT Based Smart Buildings?

PubMed Central

Moreno, M. Victoria; Úbeda, Benito; Skarmeta, Antonio F.; Zamora, Miguel A.

2014-01-01

Nowadays, buildings are increasingly expected to meet higher and more complex performance requirements. Among these requirements, energy efficiency is recognized as an international goal to promote energy sustainability of the planet. Different approaches have been adopted to address this goal, the most recent relating consumption patterns with human occupancy. In this work, we analyze what are the main parameters that should be considered to be included in any building energy management. The goal of this analysis is to help designers to select the most relevant parameters to control the energy consumption of buildings according to their context, selecting them as input data of the management system. Following this approach, we select three reference smart buildings with different contexts, and where our automation platform for energy monitoring is deployed. We carry out some experiments in these buildings to demonstrate the influence of the parameters identified as relevant in the energy consumption of the buildings. Then, in two of these buildings are applied different control strategies to save electrical energy. We describe the experiments performed and analyze the results. The first stages of this evaluation have already resulted in energy savings of about 23% in a real scenario. PMID:24887040

'Order from disorder sprung': recognition and regulation in the immune system

NASA Astrophysics Data System (ADS)

Mak, Tak W.

2003-06-01

Milton's epic poem Paradise lost supplies a colourful metaphor for the immune system and its responses to pathogens. With the role of Satan played by pathogens seeking to destroy the paradise of human health, GOD intervenes and imposes order out of chaos. In this context, GOD means 'generation of diversity': the capacity of the innate and specific immune responses to recognize and eliminate a universe of pathogens. Thus, the immune system can be thought of as an entity that self-assembles the elements required to combat bodily invasion and injury. In so doing, it brings to bear the power of specific recognition: the ability to distinguish self from non-self, and the threatening from the benign. This ability to define and protect self is evolutionarily very old. Self-recognition and biochemical and barrier defences can be detected in primitive organisms, and elements of these mechanisms are built upon in an orderly way to establish the mammalian immune system. Innate immune responses depend on the use of a limited number of germline-encoded receptors to recognize conserved molecular patterns that occur on the surfaces of a broad range of pathogens. The B and T lymphocytes of the specific immune response use complex gene-rearrangement machinery to generate a diversity of antigen receptors capable of recognizing any pathogen in the universe. Binding to receptors on both innate and specific immune-system cells triggers intricate intracellular signalling pathways that lead to new gene transcription and effector-cell activation. And yet, regulation is imposed on these responses so that Paradise is not lost to the turning of the immune system onto self-tissues, the spectre of autoimmunity. Lymphocyte activation requires multiple signals and intercellular interactions. Mechanisms exist to establish tolerance to self by the selection and elimination of cells recognizing self-antigens. Immune system cell populations are reduced by programmed cell death once the pathogen threat is resolved. Once Paradise has been regained, memory cells remain in the body to sharply reduce the impact of a second exposure to a pathogen. Vaccination programs take advantage of this capacity of the human immune system for immunological memory, sparing millions the suffering associated with disease scourges. Thus does the order of the immune response spring from the disorder of pathogen attacks, and thus is Paradise preserved.

'Order from disorder sprung': recognition and regulation in the immune system.

PubMed

Mak, Tak W

2003-06-15

Milton's epic poem Paradise lost supplies a colourful metaphor for the immune system and its responses to pathogens. With the role of Satan played by pathogens seeking to destroy the paradise of human health, GOD intervenes and imposes order out of chaos. In this context, GOD means 'generation of diversity': the capacity of the innate and specific immune responses to recognize and eliminate a universe of pathogens. Thus, the immune system can be thought of as an entity that self-assembles the elements required to combat bodily invasion and injury. In so doing, it brings to bear the power of specific recognition: the ability to distinguish self from non-self, and the threatening from the benign. This ability to define and protect self is evolutionarily very old. Self-recognition and biochemical and barrier defences can be detected in primitive organisms, and elements of these mechanisms are built upon in an orderly way to establish the mammalian immune system. Innate immune responses depend on the use of a limited number of germline-encoded receptors to recognize conserved molecular patterns that occur on the surfaces of a broad range of pathogens. The B and T lymphocytes of the specific immune response use complex gene-rearrangement machinery to generate a diversity of antigen receptors capable of recognizing any pathogen in the universe. Binding to receptors on both innate and specific immune-system cells triggers intricate intracellular signalling pathways that lead to new gene transcription and effector-cell activation. And yet, regulation is imposed on these responses so that Paradise is not lost to the turning of the immune system onto self-tissues, the spectre of autoimmunity. Lymphocyte activation requires multiple signals and intercellular interactions. Mechanisms exist to establish tolerance to self by the selection and elimination of cells recognizing self-antigens. Immune system cell populations are reduced by programmed cell death once the pathogen threat is resolved. Once Paradise has been regained, memory cells remain in the body to sharply reduce the impact of a second exposure to a pathogen. Vaccination programs take advantage of this capacity of the human immune system for immunological memory, sparing millions the suffering associated with disease scourges. Thus does the order of the immune response spring from the disorder of pathogen attacks, and thus is Paradise preserved.

Promiscuity and selectivity of bitter molecules and their receptors.

PubMed

Di Pizio, Antonella; Niv, Masha Y

2015-07-15

Bitter taste is essential for survival, as it protects against consuming poisonous compounds, which are often bitter. Bitter taste perception is mediated by bitter taste receptors (TAS2Rs), a subfamily of G-protein coupled receptors (GPCRs). The number of TAS2R subtypes is species-dependent, and varies from 3 in chicken to 50 in frog. TAS2Rs present an intriguing case for studying promiscuity: some of the receptors are still orphan, or have few known agonists, while others can be activated by numerous, structurally dissimilar compounds. The ligands also vary in the repertoire of TAS2Rs that they activate: some bitter compounds are selective toward a single TAS2R, while others activate multiple TAS2Rs. Selectivity/promiscuity profile of bitter taste receptors and their compounds was explored by a chemoinformatic approach. TAS2R-promiscuous and TAS2R-selective bitter molecules were found to differ in chemical features, such as AlogP, E-state, total charge, number of rings, globularity, and heavy atom count. This allowed the prediction of bitter ligand selectivity toward TAS2Rs. Interestingly, while promiscuous TAS2Rs are activated by both TAS2R-promiscuous and TAS2R-selective compounds, almost all selective TAS2Rs in human are activated by promiscuous compounds, which are recognized by other TAS2Rs anyway. Thus, unique ligands, that may have been the evolutionary driving force for development of selective TAS2Rs, still need to be unraveled. Copyright © 2015 Elsevier Ltd. All rights reserved.

Human Immune Response to Dengue Infections

DTIC Science & Technology

1990-07-31

flavivirus-crossreactive clone recognized dengue-l, -2, -3, and -4 virus and West Nile virus (WNV), but did not recognize yellow fever virus ( YFV ), while...three flavivirus-crossreactive clones recognized dengue-1, -2, -3 and -4 virus, WNV and YFV . We also examined the recognition of purified NS3 proteins of...dengue-l, YFV or WNV Ag. JK44 lysed target cells cultured with dengue-1, -2, and -3, but did not lyse target cells cultured with dengue-4, YFV or WNV Ag

Targeting malignant B cells with an immunotoxin against ROR1

PubMed Central

Baskar, Sivasubramanian; Wiestner, Adrian; Wilson, Wyndham H.; Pastan, Ira; Rader, Christoph

2012-01-01

The selective cell surface expression of receptor tyrosine kinase-like orphan receptor 1 (ROR1) in chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL) has made ROR1 a novel and promising target for therapeutic monoclonal antibodies (mAbs). Four mouse mAbs generated by hybridoma technology exhibited specific binding to human ROR1. Epitope mapping studies showed that two mAbs (2A2 and 2D11) recognized N-terminal epitopes in the extracellular region of ROR1 and the other two (1A1 and 1A7) recognized C-terminal epitopes. A ROR1- immunotoxin (BT-1) consisting of truncated Pseudomonas exotoxin A (PE38) and the VH and VL fragments of 2A2-IgG was made recombinantly. Both 2A2-IgG and BT-1 showed dose-dependent and selective binding to primary CLL and MCL cells and MCL cell lines. Kinetic analyses revealed 0.12-nM (2A2-IgG) to 65-nM (BT-1) avidity/affinity to hROR1, depicting bivalent and monovalent interactions, respectively. After binding to cell surface ROR1, 2A2-IgG and BT-1 were partially internalized by primary CLL cells and MCL cell lines, and BT-1 induced profound apoptosis of ROR1-expressing MCL cell lines in vitro (EC50 = 16 pM–16 nM), but did not affect ROR1-negative cell lines. Our data suggest that ROR1-immunotoxins such as BT-1 could serve as targeted therapeutic agents for ROR1-expressing B cell malignancies and other cancers. PMID:22531447

Evolution, revolution and heresy in the genetics of infectious disease susceptibility

PubMed Central

Hill, Adrian V. S.

2012-01-01

Infectious pathogens have long been recognized as potentially powerful agents impacting on the evolution of human genetic diversity. Analysis of large-scale case–control studies provides one of the most direct means of identifying human genetic variants that currently impact on susceptibility to particular infectious diseases. For over 50 years candidate gene studies have been used to identify loci for many major causes of human infectious mortality, including malaria, tuberculosis, human immunodeficiency virus/acquired immunodeficiency syndrome, bacterial pneumonia and hepatitis. But with the advent of genome-wide approaches, many new loci have been identified in diverse populations. Genome-wide linkage studies identified a few loci, but genome-wide association studies are proving more successful, and both exome and whole-genome sequencing now offer a revolutionary increase in power. Opinions differ on the extent to which the genetic component to common disease susceptibility is encoded by multiple high frequency or rare variants, and the heretical view that most infectious diseases might even be monogenic has been advocated recently. Review of findings to date suggests that the genetic architecture of infectious disease susceptibility may be importantly different from that of non-infectious diseases, and it is suggested that natural selection may be the driving force underlying this difference. PMID:22312051

Discovery of human scFvs that cross-neutralize the toxic effects of B. jararacussu and C. d. terrificus venoms.

PubMed

Silva, Luciano C; Pucca, Manuela B; Pessenda, Gabriela; Campos, Lucas B; Martinez, Edson Z; Cerni, Felipe A; Barbosa, José E

2018-01-01

Accidents involving venomous snakes are a public health problem worldwide, causing a large number of deaths per year. In Brazil, the majority of accidents are caused by the Bothrops and Crotalus genera, which are responsible for approximately 80% of severe envenoming cases. The cross-neutralization of snake venoms by antibodies is an important issue for development of more effective treatments. Our group has previously reported the construction of human monoclonal antibody fragments towards Bothrops jararacussu and Crotalus durissus terrificus' venoms. This study aimed to select human single-chain variable fragments (scFvs) that recognize both bothropic and crotalic crude venoms following venoms neutralizing capacity in vitro and in vivo. The cross-reactivity of Cro-Bothrumabs were demonstrated by ELISA and in vitro and in vivo experiments showed that a combination of scFvs neutralizes in vitro toxic activities (e.g. indirect hemolysis and plasma-clotting) of crotalic and bothropic venoms as well as prolonged survival time of envenomed animals. Our results may contribute to the development of the first human polyvalent antivenom against Bothrops jararacussu and Crotalus durissus terrificus venoms, overcoming some undesirable effects caused by conventional serotherapy. Copyright © 2017 Elsevier B.V. All rights reserved.

Integrating human health and ecological concerns in risk assessments.

PubMed

Cirone, P A; Bruce Duncan, P

2000-11-03

The interconnections between ecosystems, human health and welfare have been increasingly recognized by the US government, academia, and the public. This paper continues this theme by addressing the use of risk assessment to integrate people into a single assessment. In a broad overview of the risk assessment process we stress the need to build a conceptual model of the whole system including multiple species (humans and other ecological entities), stressors, and cumulative effects. We also propose converging landscape ecology and evaluation of ecosystem services with risk assessment to address these cumulative responses. We first look at how this integration can occur within the problem formulation step in risk assessment where the system is defined, a conceptual model created, a subset of components and functions selected, and the analytical framework decided in a context that includes the management decisions. A variety of examples of problem formulations (salmon, wild insects, hyporheic ecosystems, ultraviolet (UV) radiation, nitrogen fertilization, toxic chemicals, and oil spills) are presented to illustrate how treating humans as components of the landscape can add value to risk assessments. We conclude that the risk assessment process should help address the urgent needs of society in proportion to importance, to provide a format to communicate knowledge and understanding, and to inform policy and management decisions.

Human Rights: The Struggle for Freedom, Dignity and Equality. Resource Guide.

ERIC Educational Resources Information Center

Connecticut State Dept. of Education, Hartford.

Every human being deserves the right to live in freedom and dignity. Yet human rights violations dominate the headlines. In addition to becoming sensitive to human pain and suffering, young adults must also begin the lifelong process of creating, recognizing, and exercising options. This resource guide contains suggested questions and projects…

"The Path of Social Justice": A Human Rights History of Social Justice Education

ERIC Educational Resources Information Center

Grant, Carl A.; Gibson, Melissa Leigh

2013-01-01

Although not often recognized, social justice education in the U.S. is historically and philosophically tied to the twentieth century's human rights initiatives. The efforts of human rights pioneers, such as those who authored the Universal Declaration of Human Rights, have indelibly shaped social justice efforts, including within education, in…

The Role of International Human Rights Norms in the Liberalization of Abortion Laws Globally.

PubMed

Fine, Johanna B; Mayall, Katherine; Sepúlveda, Lilian

2017-06-01

International and regional human rights norms have evolved significantly to recognize that the denial of abortion care in a range of circumstances violates women's and girls' fundamental human rights. These increasingly progressive standards have played a critical role in transforming national-level abortion laws by both influencing domestic high court decisions on abortion and serving as a critical resource in advancing law and policy reform. Courts in countries such as Argentina, Bolivia, Brazil, Colombia, and Nepal have directly incorporated these standards into groundbreaking cases liberalizing abortion laws and increasing women's access to safe abortion services, demonstrating the influence of these human rights standards in advancing women's reproductive freedom. These norms have also underpinned national-level abortion law and policy reform, including in countries such as Spain, Rwanda, Uruguay, and Peru. As these human rights norms further evolve and increasingly recognize abortion as a human rights imperative, these standards have the potential to bolster transformative jurisprudence and law and policy reform advancing women's and girls' full reproductive autonomy.

Using a social robot to teach gestural recognition and production in children with autism spectrum disorders.

PubMed

So, Wing-Chee; Wong, Miranda Kit-Yi; Lam, Carrie Ka-Yee; Lam, Wan-Yi; Chui, Anthony Tsz-Fung; Lee, Tsz-Lok; Ng, Hoi-Man; Chan, Chun-Hung; Fok, Daniel Chun-Wing

2017-07-04

While it has been argued that children with autism spectrum disorders are responsive to robot-like toys, very little research has examined the impact of robot-based intervention on gesture use. These children have delayed gestural development. We used a social robot in two phases to teach them to recognize and produce eight pantomime gestures that expressed feelings and needs. Compared to the children in the wait-list control group (N = 6), those in the intervention group (N = 7) were more likely to recognize gestures and to gesture accurately in trained and untrained scenarios. They also generalized the acquired recognition (but not production) skills to human-to-human interaction. The benefits and limitations of robot-based intervention for gestural learning were highlighted. Implications for Rehabilitation Compared to typically-developing children, children with autism spectrum disorders have delayed development of gesture comprehension and production. Robot-based intervention program was developed to teach children with autism spectrum disorders recognition (Phase I) and production (Phase II) of eight pantomime gestures that expressed feelings and needs. Children in the intervention group (but not in the wait-list control group) were able to recognize more gestures in both trained and untrained scenarios and generalize the acquired gestural recognition skills to human-to-human interaction. Similar findings were reported for gestural production except that there was no strong evidence showing children in the intervention group could produce gestures accurately in human-to-human interaction.

Millions of missing girls: from fetal sexing to high technology sex selection in India.

PubMed

George, Sabu M

2006-07-01

The morality and acceptability of using prenatal diagnosis for sex selection is being extensively debated around the world as advances in assisted reproductive technologies (ART) and embryology have enabled selective implantation of embryos of the desired sex (George and Dahiya, 1998; Savulescu, 1999; Raphael, 2002; Harris, 2005; Robertson, 2005; Snider, 2005). Sophisticated methods of separation of semen, originally developed for cattle breeding, are being used for human sex selection. Recently, non-invasive methods of fetal sex determination in the first trimester (from 6 weeks) of pregnancy have also emerged (Hahn and Chitty, 2005). Market forces that promote sex selection along with libertarian ideologues have assisted in blurring the ethical limits (Paul, 2001; President's Council on Bioethics, 2003). The widespread misuse of sex selection for eliminating girls before birth in India and among the Indian diaspora needs to be brought into the global 'intellectual discourse'. It is imperative that Western ethicists recognize the genocidal nature of sex selection taking place in certain Asian countries. Even if they believe that these trends will not affect mainstream Western societies, the promotion or tolerance of sex selection amounts to a 'crime of silence' against this ongoing genocide in China and India. I have been concerned with issues of the girl child in India for over two decades and sex selection among Asian Indians in North America (George et al., 1992; George et al., 1993; George and Dahiya, 1998). This article examines the missing millions of girls, but will not consider the 1980s campaign against fetal sex determination, Indian feminists' recognition of sex selection as violence against women (unlike several Western feminists, Moazam, 2004), or the Government's response to regulate prenatal diagnostic techniques in 1994 (George and Dahiya, 1998; George, 2002). Copyright 2006 John Wiley & Sons, Ltd.

Mother Knows Best: Epigenetic Inheritance, Maternal Effects, and the Evolution of Human Intelligence

ERIC Educational Resources Information Center

Bjorklund, David F.

2006-01-01

Contemporary evolution biology has recognized the role of development in evolution. Evolutionarily oriented psychologists have similarly recognized the role that behavioral plasticity, particularly early in development, may have had on the evolution of species, harking back to the ideas of Baldwin (the Baldwin effect). Epigenetic theories of…

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

Wu, Kailang; Li, Weikai; Peng, Guiqing

NL63 coronavirus (NL63-CoV), a prevalent human respiratory virus, is the only group I coronavirus known to use angiotensin-converting enzyme 2 (ACE2) as its receptor. Incidentally, ACE2 is also used by group II SARS coronavirus (SARS-CoV). We investigated how different groups of coronaviruses recognize the same receptor, whereas homologous group I coronaviruses recognize different receptors. We determined the crystal structure of NL63-CoV spike protein receptor-binding domain (RBD) complexed with human ACE2. NL63-CoV RBD has a novel {beta}-sandwich core structure consisting of 2 layers of {beta}-sheets, presenting 3 discontinuous receptor-binding motifs (RBMs) to bind ACE2. NL63-CoV and SARS-CoV have no structural homologymore » in RBD cores or RBMs; yet the 2 viruses recognize common ACE2 regions, largely because of a 'virus-binding hotspot' on ACE2. Among group I coronaviruses, RBD cores are conserved but RBMs are variable, explaining how these viruses recognize different receptors. These results provide a structural basis for understanding viral evolution and virus-receptor interactions.« less

Application of bacteriophages in post-harvest control of human pathogenic and food spoiling bacteria.

PubMed

Pérez Pulido, Rubén; Grande Burgos, Maria José; Gálvez, Antonio; Lucas López, Rosario

2016-10-01

Bacteriophages have attracted great attention for application in food biopreservation. Lytic bacteriophages specific for human pathogenic bacteria can be isolated from natural sources such as animal feces or industrial wastes where the target bacteria inhabit. Lytic bacteriophages have been tested in different food systems for inactivation of main food-borne pathogens including Listeria monocytogenes, Staphylococcus aureus, Escherichia coli O157:H7, Salmonella enterica, Shigella spp., Campylobacter jejuni and Cronobacter sakazkii, and also for control of spoilage bacteria. Application of lytic bacteriophages could selectively control host populations of concern without interfering with the remaining food microbiota. Bacteriophages could also be applied for inactivation of bacteria attached to food contact surfaces or grown as biofilms. Bacteriophages may receive a generally recognized as safe status based on their lack of toxicity and other detrimental effects to human health. Phage preparations specific for L. monocytogenes, E. coli O157:H7 and S. enterica serotypes have been commercialized and approved for application in foods or as part of surface decontamination protocols. Phage endolysins have a broader host specificity compared to lytic bacteriophages. Cloned endolysins could be used as natural preservatives, singly or in combination with other antimicrobials such as bacteriocins.

Modeling activity recognition of multi resident using label combination of multi label classification in smart home

NASA Astrophysics Data System (ADS)

Mohamed, Raihani; Perumal, Thinagaran; Sulaiman, Md Nasir; Mustapha, Norwati; Zainudin, M. N. Shah

2017-10-01

Pertaining to the human centric concern and non-obtrusive way, the ambient sensor type technology has been selected, accepted and embedded in the environment in resilient style. Human activities, everyday are gradually becoming complex and thus complicate the inferences of activities when it involving the multi resident in the same smart environment. Current works solutions focus on separate model between the resident, activities and interactions. Some study use data association and extra auxiliary of graphical nodes to model human tracking information in an environment and some produce separate framework to incorporate the auxiliary for interaction feature model. Thus, recognizing the activities and which resident perform the activity at the same time in the smart home are vital for the smart home development and future applications. This paper will cater the above issue by considering the simplification and efficient method using the multi label classification framework. This effort eliminates time consuming and simplifies a lot of pre-processing tasks comparing with previous approach. Applications to the multi resident multi label learning in smart home problems shows the LC (Label Combination) using Decision Tree (DT) as base classifier can tackle the above problems.

Shining light on skin pigmentation: the darker and the brighter side of effects of UV radiation.

PubMed

Maddodi, Nityanand; Jayanthy, Ashika; Setaluri, Vijayasaradhi

2012-01-01

The term barrier function as applied to human skin often connotes the physical properties of this organ that provides protection from its surrounding environment. This term does not generally include skin pigmentation. However, skin pigmentation, which is the result of melanin produced in melanocytes residing in the basal layer of the skin and exported to the keratinocytes in the upper layers, serves equally important protective function. Indeed, changes in skin pigmentation are often the most readily recognized indicators of exposure of skin to damaging agents, especially to natural and artificial radiation in the environment. Several recent studies have shed new light on (1) the mechanisms involved in selective effects of subcomponents of UV radiation on human skin pigmentation and (2) the interactive influences between keratinocytes and melanocytes, acting as "epidermal melanin unit," that manifest as changes in skin pigmentation in response to exposure to various forms of radiation. This article provides a concise review of our current understanding of the effects of the nonionizing solar radiation, at cellular and molecular levels, on human skin pigmentation. © 2012 Wiley Periodicals, Inc. Photochemistry and Photobiology © 2012 The American Society of Photobiology.

If exposure to aluminium in antiperspirants presents health risks, its content should be reduced.

PubMed

Pineau, Alain; Fauconneau, Bernard; Sappino, André-Pascal; Deloncle, Roger; Guillard, Olivier

2014-04-01

Since aluminium (Al) pervades our environment, the scientific community has for many years raised concerns regarding its safety in humans. Al is present in numerous cosmetics such as antiperspirants, lipsticks and sunscreens. Al chlorohydrate is the active antiperspirant agent in underarm cosmetics and may constitute for Al a key exposure route to the human body and a potential source of damage. An in vitro study has demonstrated that Al from antiperspirant can be absorbed through viable human stripped skin. The potential toxicity of Al has been clearly shown and recent works convincingly argue that Al could be involved in cancerogenic processes. Nowadays, for example, Al is suspected of being involved in breast cancer. Recent work in cells in culture has lent credence to the hypothesis that this metal could accumulate in the mammary gland and selectively interfere with the biological properties of breast epithelial cells, thereby promoting a cascade of alterations reminiscent of the early phases of malignant transformation. In addition, several studies suggest that the presence of Al in human breast could influence metastatic process. As a consequence, given that the toxicity of Al has been widely recognized and that it is not a physiological component in human tissues, reducing the concentration of this metal in antiperspirants is a matter of urgency. Copyright © 2013 Elsevier GmbH. All rights reserved.

Quantitative Risk Assessment of Human Trichinellosis Caused by Consumption of Pork Meat Sausages in Argentina.

PubMed

Sequeira, G J; Zbrun, M V; Soto, L P; Astesana, D M; Blajman, J E; Rosmini, M R; Frizzo, L S; Signorini, M L

2016-03-01

In Argentina, there are three known species of genus Trichinella; however, Trichinella spiralis is most commonly associated with domestic pigs and it is recognized as the main cause of human trichinellosis by the consumption of products made with raw or insufficiently cooked pork meat. In some areas of Argentina, this disease is endemic and it is thus necessary to develop a more effective programme of prevention and control. Here, we developed a quantitative risk assessment of human trichinellosis following pork meat sausage consumption, which may be used to identify the stages with greater impact on the probability of acquiring the disease. The quantitative model was designed to describe the conditions in which the meat is produced, processed, transported, stored, sold and consumed in Argentina. The model predicted a risk of human trichinellosis of 4.88 × 10(-6) and an estimated annual number of trichinellosis cases of 109. The risk of human trichinellosis was sensitive to the number of Trichinella larvae that effectively survived the storage period (r = 0.89), the average probability of infection (PPinf ) (r = 0.44) and the storage time (Storage) (r = 0.08). This model allowed assessing the impact of different factors influencing the risk of acquiring trichinellosis. The model may thus help to select possible strategies to reduce the risk in the chain of by-products of pork production. © 2015 Blackwell Verlag GmbH.

Human CD8 T lymphocytes recognize Mycobacterium tuberculosis antigens presented by HLA-E during active tuberculosis and express type 2 cytokines.

PubMed

Caccamo, Nadia; Pietra, Gabriella; Sullivan, Lucy C; Brooks, Andrew G; Prezzemolo, Teresa; La Manna, Marco P; Di Liberto, Diana; Joosten, Simone A; van Meijgaarden, Krista E; Di Carlo, Paola; Titone, Lucina; Moretta, Lorenzo; Mingari, Maria C; Ottenhoff, Tom H M; Dieli, Francesco

2015-04-01

CD8 T cells contribute to protective immunity against Mycobacterium tuberculosis. In humans, M. tuberculosis reactive CD8 T cells typically recognize peptides associated to classical MHC class Ia molecules, but little information is available on CD8 T cells recognizing M. tuberculosis Ags presented by nonclassical MHC class Ib molecules. We show here that CD8 T cells from tuberculosis (TB) patients recognize HLA-E-binding M. tuberculosis peptides in a CD3/TCR αβ mediated and CD8-dependent manner, and represent an additional type of effector cells playing a role in immune response to M. tuberculosis during active infection. HLA-E-restricted recognition of M. tuberculosis peptides is detectable by a significant enhanced ex vivo frequency of tetramer-specific circulating CD8 T cells during active TB. These CD8 T cells produce type 2 cytokines upon antigenic in vitro stimulation, help B cells for Ab production, and mediate limited TRAIL-dependent cytolytic and microbicidal activity toward M. tuberculosis infected target cells. Our results, together with the finding that HLA-E/M. tuberculosis peptide specific CD8 T cells are detected in TB patients with or without HIV coinfection, suggest that this is a new human T-cell population that participates in immune response in TB. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Production of a germline-humanized cetuximab scFv and evaluation of its activity in recognizing EGFR- overexpressing cancer cells.

PubMed

Banisadr, Arsham; Safdari, Yaghoub; Kianmehr, Anvarsadat; Pourafshar, Mahdieh

2018-04-03

The aim of this study was to produce a humanized single chain antibody (scFv) as a potential improved product design to target EGFR (Epidermal Growth Factor Receptor) overexpressing cancer cells. To this end, CDR loops of cetuximab (an FDA-approved anti-EGFR antibody) were grafted on framework regions derived from type 3 (VH3 and VL3 kappa) human germline sequences to obtain recombinant VH and VL domainslinked together with a flexible linker [(Gly 4 Ser) 3 ] to form a scFv. Codon optimized synthetic gene encoding the scFv (with NH2-VH-linker-VL-COOH orientation) was expressed in E. coli Origami™ 2(DE3) cells and the resultant scFv purified by using Ni-NTA affinity chromatography. The scFv, called cet.Hum scFv, was evaluated in ELISA and immunoblot to determine whether it can recognize EGFR. The scFv was able to recognize EGFR over-expressing cancer cells (A-431) but failed to detect cancer cells with low levels of EGFR (MCF-7 cells). Although the affinity of the scFv forA-431 cells was 9 fold lower than that of cetuximab, it was strong enough to recognize these cells. Considering its ability to bind EGFR molecules, the scFv may exhibit a potential application for the detection of EGFR-overexpressing cancer cells.

Study of recognizing multiple persons' complicated hand gestures from the video sequence acquired by a moving camera

NASA Astrophysics Data System (ADS)

Dan, Luo; Ohya, Jun

2010-02-01

Recognizing hand gestures from the video sequence acquired by a dynamic camera could be a useful interface between humans and mobile robots. We develop a state based approach to extract and recognize hand gestures from moving camera images. We improved Human-Following Local Coordinate (HFLC) System, a very simple and stable method for extracting hand motion trajectories, which is obtained from the located human face, body part and hand blob changing factor. Condensation algorithm and PCA-based algorithm was performed to recognize extracted hand trajectories. In last research, this Condensation Algorithm based method only applied for one person's hand gestures. In this paper, we propose a principal component analysis (PCA) based approach to improve the recognition accuracy. For further improvement, temporal changes in the observed hand area changing factor are utilized as new image features to be stored in the database after being analyzed by PCA. Every hand gesture trajectory in the database is classified into either one hand gesture categories, two hand gesture categories, or temporal changes in hand blob changes. We demonstrate the effectiveness of the proposed method by conducting experiments on 45 kinds of sign language based Japanese and American Sign Language gestures obtained from 5 people. Our experimental recognition results show better performance is obtained by PCA based approach than the Condensation algorithm based method.

The historical Latin and etymology of selected anatomical terms of the larynx.

PubMed

Lydiatt, Daniel D; Bucher, Gregory S

2010-03-01

The etymological evolution of the anatomical terms larynx, cricoid, glottis, epiglottis, and thyroid (cartilage) dates to antiquity. Human dissection replaced animal in the 16th and 17th centuries and terms evolved. This evolution was recorded in the literature largely in Latin. We translated key studies of laryngeal anatomy from the 16th century to better understand this evolution. We present the Latin with our translations, and historical commentary as essential to this understanding. Vesalius favored the Latin scutiform (shield) for the thyroid cartilage, but recognized peltalis (shield). The Basle Nomina Anatomica (BNA) chose the Greek thyroid (theta upsilon rho epsilon omicron epsilon iota delta eta) for modern convention. Vesalius used the name "innominate" for the cricoid cartilage, but described its resemblance to a ring, drawn in the margin of the Fabrica. Krikoid, the Greek for ring shaped, was adopted by the BNA. Although the term arytenoid was used for centuries, Vesalius argued the Greek name referred to the spout of a cup or ladle. He recognized the human arytenoids as two separate cartilages as opposed to single in certain animals. The glottis was defined by Vesalius as the vocal fold or rima glottidis of today, and he advanced its function by understanding the paired, mobile arytenoid cartilages. He defined the function of the epiglottis and first described the pre-epiglottic space. Vesalius' student at Padua, Italy, Columbo contributed to anatomical knowledge, but animosity between them clouded the record. Harvey, working 75 years later in England, offers an evolutionary window from Vesalius. Harvey's laryngeal studies preceded by a decade his groundbreaking studies on the circulation of blood.

The Humanities Are Not a Luxury: A Manifesto for the Twenty-First Century

ERIC Educational Resources Information Center

Smith, Martha Nell

2011-01-01

The humanities are at the heart of knowing about the human condition; they are not a luxury. The erosion of support for the humanities and the perennial anxiety about the state of the humanities are systemic. The author contends that until people acknowledge this fact, they will keep lurching from one point to another, unable to recognize the…

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

Yu, Zongchao; Wang, Fengqin, E-mail: wangfengqin@tjpu.edu.cn; Lin, Xiangyi

Metal-organic frameworks (MOFs) are porous crystalline materials with high potential for applications in fluorescence sensors. In this work, two solvent-induced Zn(II)–based metal-organic frameworks, Zn{sub 3}L{sub 3}(DMF){sub 2} (1) and Zn{sub 3}L{sub 3}(DMA){sub 2}(H{sub 2}O){sub 3} (2) (L=4,4′-stilbenedicarboxylic acid), were investigated as selective sensing materials for detection of nitroaromatic compounds and metal ions. The sensing experiments show that 1 and 2 both exhibit selective fluorescence quenching toward nitroaniline with a low detection limit. In addition, 1 exhibits high selectivity for detection of Fe{sup 3+} and Al{sup 3+} by significant fluorescence quenching or enhancement effect. While for 2, it only exhibits significantmore » fluorescence quenching effect for Fe{sup 3+}. The results indicate that 1 and 2 are both promising fluorescence sensors for detecting and recognizing nitroaniline and metal ions with high sensitivity and selectivity. - Graphical abstract: Two MOFs have been selected as the fluorescence sensing materials for selectively sensing mitroaromatic compounds and metal ions. The high selectivity makes them promising fluorescence sensors for detecting and recognizing nitroaniline and Fe{sup 3+} or Al{sup 3+}.« less

Landfill gas control at military installations. Final report

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

Shafer, R.A.; Renta-Babb, A.; Bandy, J.T.

1984-01-01

This report provides information useful to Army personnel responsible for recognizing and solving potential problems from gas generated by landfills. Information is provided on recognizing and gauging the magnitude of landfill gas problems; selecting appropriate gas control strategies, procedures, and equipment; use of computer modeling to predict gas production and migration and the success of gas control devices; and safety considerations.

Research Experiences and Mentoring Practices in Selected East Asian Graduate Programs: Predictors of Research Productivity among Doctoral Students in Molecular Biology

ERIC Educational Resources Information Center

Ynalvez, Ruby; Garza-Gongora, Claudia; Ynalvez, Marcus Antonius; Hara, Noriko

2014-01-01

Although doctoral mentors recognize the benefits of providing quality advisement and close guidance, those of sharing project management responsibilities with mentees are still not well recognized. We observed that mentees, who have the opportunity to co-manage projects, generate more written output. Here we examine the link between research…

Recognizing the 65th anniversary of the Universal Declaration of Human Rights and the celebration of "Human Rights Day".

THOMAS, 113th Congress

Rep. Lowenthal, Alan S. [D-CA-47

2013-12-10

House - 01/10/2014 Referred to the Subcommittee on Africa, Global Health, Global Human Rights and International Organizations. (All Actions) Tracker: This bill has the status IntroducedHere are the steps for Status of Legislation:

Development of Monoclonal Antibodies Recognizing Linear Epitope: Illustration by Three Bacillus thuringiensis Crystal Proteins of Genetically Modified Cotton, Maize, and Tobacco.

PubMed

Cao, Zhen; Zhang, Wei; Ning, Xiangxue; Wang, Baomin; Liu, Yunjun; Li, Qing X

2017-11-22

Bacillus thuringiensis Cry1Ac, Cry1Ia1, and Cry1Ie are δ-endotoxin insecticidal proteins widely implemented in genetically modified organisms (GMO), such as cotton, maize, and potato. Western blot assay integrates electrophoresis separation power and antibody high specificity for monitoring specific exogenous proteins expressed in GMO. Procedures for evoking monoclonal antibody (mAb) for Western blot were poorly documented. In the present study, Cry1Ac partially denatured at 100 °C for 5 min was used as an immunogen to develop mAbs selectively recognizing a linear epitope of Cry1Ac for Western blot. mAb 5E9C6 and 3E6E2 selected with sandwich ELISA strongly recognized the heat semidenatured Cry1Ac. Particularly, 3E6E2 recognized both E. coli and cotton seed expressed Cry1Ac in Western blot. Such strategy of using partially denatured proteins as immunogens and using sandwich ELISA for mAb screening was also successfully demonstrated with production of mAbs against Cry1Ie for Western blot assay in maize.

Award for Distinguished Senior Career Contributions to Psychology in the Public Interest: José Toro-Alfonso.

PubMed

2016-11-01

The APA Awards for Distinguished Contributions to Psychology in the Public Interest recognize persons who have advanced psychology as a science and/or profession by a single extraordinary achievement or a lifetime of outstanding contributions in the public interest. The 2016 corecipient of the Award for Distinguished Senior Career Contributions to Psychology in the Public Interest is José Toro-Alfonso, who was posthumously given this award for his commitment to "issues of inequity, diversity, and to the alleviation of human suffering particularly among Latino/Latina and LGBTQ communities." He "pioneered HIV/AIDS-related services for youth, women, gay, and transgender populations," and Toro-Alfonso's award citation, biography, and a selected bibliography are presented here. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

New approaches for Helicobacter vaccine development--difficulties and progress.

PubMed

Jagusztyn-Krynicka, Elzbieta K; Godlewska, Renata

2008-01-01

Despite the enormous progress in understanding the process of bacterial pathogenesis and interactions of pathogens with eucaryotic cells the infectious diseases still remain the main cause of human premature deaths. It is now recognized that Helicobacter pylori infects about half of the world's population. Based on results of clinical studies the World Health Organization has assigned H. pylori as a class I carcinogen. The review presents new achievements aimed at construction efficient and safe anti-Helicobacter vaccine. We discuss the new global technologies such as immunoproteomics employed for selecting new candidates for vaccine construction as well as new vaccine delivery systems. The review presents also our knowledge concerning H. pylori interaction with immune system which might facilitate modulation of the host immune system by specific adjuvant included into vaccine.

Knowledge based systems: A preliminary survey of selected issues and techniques

NASA Technical Reports Server (NTRS)

Dominick, Wayne D. (Editor); Kavi, Srinu

1984-01-01

It is only recently that research in Artificial Intelligence (AI) is accomplishing practical results. Most of these results can be attributed to the design and use of expert systems (or Knowledge-Based Systems, KBS) - problem-solving computer programs that can reach a level of performance comparable to that of a human expert in some specialized problem domain. But many computer systems designed to see images, hear sounds, and recognize speech are still in a fairly early stage of development. In this report, a preliminary survey of recent work in the KBS is reported, explaining KBS concepts and issues and techniques used to construct them. Application considerations to construct the KBS and potential KBS research areas are identified. A case study (MYCIN) of a KBS is also provided.

Murphy's law-if anything can go wrong, it will: Problems in phage electron microscopy.

PubMed

Ackermann, Hans-W; Tiekotter, Kenneth L

2012-04-01

The quality of bacteriophage electron microscopy appears to be on a downward course since the 1980s. This coincides with the introduction of digital electron microscopes and a general lowering of standards, possibly due to the disappearance of several world-class electron microscopists The most important problem seems to be poor contrast. Positive staining is frequently not recognized as an undesirable artifact. Phage parts, bacterial debris, and aberrant or damaged phage particles may be misdiagnosed as bacterial viruses. Digital electron microscopes often seem to be operated without magnification control because this is difficult and inconvenient. In summary, most phage electron microscopy problems may be attributed to human failure. Journals are a last-ditch defense and have a heavy responsibility in selecting competent reviewers and rejecting, or not, unsatisfactory articles.

Modeling the Blood-Brain Barrier in a 3D triple co-culture microfluidic system.

PubMed

Adriani, G; Ma, D; Pavesi, A; Goh, E L K; Kamm, R D

2015-01-01

The need for a blood-brain barrier (BBB) model that accurately mimics the physiological characteristics of the in-vivo situation is well-recognized by researchers in academia and industry. However, there is currently no in-vitro model allowing studies of neuronal growth and/or function influenced by factors from the blood that cross through the BBB. Therefore, we established a 3D triple co-culture microfluidic system using human umbilical vein endothelial cells (HUVEC) together with primary rat astrocytes and neurons. Immunostaining confirmed the successful triple co-culture system consisting of an intact BBB with tight intercellular junctions in the endothelial monolayer. The BBB selective permeability was determined by a fluorescent-based assay using dextrans of different molecular weights. Finally, neuron functionality was demonstrated by calcium imaging.

Genetic analysis and antigenic characterization of swine origin influenza viruses isolated from humans in the United States, 1990-2010.

PubMed

Shu, Bo; Garten, Rebecca; Emery, Shannon; Balish, Amanda; Cooper, Lynn; Sessions, Wendy; Deyde, Varough; Smith, Catherine; Berman, LaShondra; Klimov, Alexander; Lindstrom, Stephen; Xu, Xiyan

2012-01-05

Swine influenza viruses (SIV) have been recognized as important pathogens for pigs and occasional human infections with swine origin influenza viruses (SOIV) have been reported. Between 1990 and 2010, a total of twenty seven human cases of SOIV infections have been identified in the United States. Six viruses isolated from 1990 to 1995 were recognized as classical SOIV (cSOIV) A(H1N1). After 1998, twenty-one SOIV recovered from human cases were characterized as triple reassortant (tr_SOIV) inheriting genes from classical swine, avian and human influenza viruses. Of those twenty-one tr_SOIV, thirteen were of A(H1N1), one of A(H1N2), and seven of A(H3N2) subtype. SOIV characterized were antigenically and genetically closely related to the subtypes of influenza viruses circulating in pigs but distinct from contemporary influenza viruses circulating in humans. The diversity of subtypes and genetic lineages in SOIV cases highlights the importance of continued surveillance at the animal-human interface. Copyright © 2011. Published by Elsevier Inc.

Is vitronectin the velcro that binds the gametes together?

PubMed

Fusi, F M; Bernocchi, N; Ferrari, A; Bronson, R A

1996-11-01

Evidence has been presented that the adhesion of human spermatozoa to the oolemma is mediated by integrins recognizing the Arg-Gly-Asp sequence (RGD). Fibronectin and vitronectin, glycoproteins that contain functional RGD sequences, are both present on human spermatozoa, and integrins that recognize these ligands have been detected on spermatozoa and eggs. In this work, we studied the effects of oligopeptides specifically designed to block fibronectin or vitronectin receptors on the interaction of human spermatozoa with zona-free hamster oocytes. GRGDdSP, a peptide blocking cell attachment to fibronectin, was without effect, while GdRGDSP, which blocks both fibronectin and vitronectin receptors, significantly inhibited the binding of human spermatozoa to the oolemma of zona-free hamster eggs, in a concentration-dependent manner, over a range 1-100 microM. As these experiments suggested that a vitronectin receptor plays a role in sperm-oolemmal adhesion, we performed a series of experiments studying the effects of exogenous vitronectin, when added to spermatozoa and oocytes, on gamete interactions. Sperm-oolemmal adherence, as well as sperm aggregation, was promoted by vitronectin, over range of 2.2 nM to 1 microM, but only in the presence of calcium ions. We propose that vitronectin released during the sperm acrosome reaction is recognized by both gametes and plays a role in their adhesion.

29 CFR 30.5 - Selection of apprentices.

Code of Federal Regulations, 2013 CFR

2013-07-01

... the general education development tests recognized by the State or local public instruction authority shall be evidence of educational achievement. Education requirements shall be applied uniformly to all... establish goals and timetables for the selection of minority and female apprentices, unless the sponsor...

29 CFR 30.5 - Selection of apprentices.

Code of Federal Regulations, 2014 CFR

2014-07-01

... the general education development tests recognized by the State or local public instruction authority shall be evidence of educational achievement. Education requirements shall be applied uniformly to all... establish goals and timetables for the selection of minority and female apprentices, unless the sponsor...

29 CFR 30.5 - Selection of apprentices.

Code of Federal Regulations, 2012 CFR

2012-07-01

... the general education development tests recognized by the State or local public instruction authority shall be evidence of educational achievement. Education requirements shall be applied uniformly to all... establish goals and timetables for the selection of minority and female apprentices, unless the sponsor...

Characterization of preferential flow pathways in a siliciclastic aquifer system using human enteric viruses and groundwater geochemistry

USDA-ARS?s Scientific Manuscript database

Human enteric viruses have been recognized as an emerging groundwater contaminant and are found only in human waste. In urban environments the most likely source of human waste is from sanitary sewers. Determining the travel time for near-surface contaminants to reach deep public supply wells is i...

Influenza virus resistance to human neutralizing antibodies.

PubMed

Crowe, James E

2012-01-01

The human antibody repertoire has an exceptionally large capacity to recognize new or changing antigens through combinatorial and junctional diversity established at the time of V(D)J recombination and through somatic hypermutation. Influenza viruses exhibit a relentless capacity to escape the human antibody response by altering the amino acids of their surface proteins in hypervariable domains that exhibit a high level of structural plasticity. Both parties in this high-stakes game of shape shifting drive structural evolution of their functional proteins (the B cell receptor/antibody on one side and the viral hemagglutinin and neuraminidase proteins on the other) using error-prone polymerase systems. It is likely that most of the genetic mutations that occur in these systems are deleterious, resulting in the failure of the B cell or virus with mutations to propagate in the immune repertoire or viral quasispecies. A subset of mutations is tolerated in functional surface proteins that enter the B cell or virus progeny pool. In both cases, selection occurs in the population of mutated and unmutated species. In cases where the functional avidity of the B cell receptor is increased significantly, that clone may be selected for preferential expansion. In contrast, an influenza virus that "escapes" the inhibitory effect of secreted antibodies may represent a high proportion of the progeny virus in that host. The recent paper by O'Donnell et al. [C. D. O'Donnell et al., mBio 3(3):e00120-12, 2012] identifies a mechanism for antibody resistance that does not require escape from binding but rather achieves a greater efficiency in replication.

Novelty-seeking DRD4 polymorphisms are associated with human migration distance out-of-Africa after controlling for neutral population gene structure.

PubMed

Matthews, Luke J; Butler, Paul M

2011-07-01

Numerous lines of evidence suggest that Homo sapiens evolved as a distinct species in Africa by 150,000 years before the present (BP) and began major migrations out-of-Africa ∼50,000 BP. By 20,000 BP, our species had effectively colonized the entire Old World, and by 12,000 BP H. sapiens had a global distribution. We propose that this rapid migration into new habitats selected for individuals with low reactivity to novel stressors. Certain dopamine receptor D4 (DRD4) polymorphisms are associated with low neuronal reactivity and increased exploratory behavior, novelty seeking, and risk taking, collectively considered novelty-seeking trait (NS). One previous report (Chen et al.: Evol Hum Behav 20 (1999) 309-324) demonstrated a correlation between migratory distance and the seven-repeat (7R) VNTR DRD4 allele at exon 3 for human populations. This study, however, failed to account for neutral genetic processes (drift and admixture) that might create such a correlation in the absence of natural selection. Furthermore, additional loci surrounding DRD4 are now recognized to influence NS. Herein we account for neutral genetic structure by modeling the nonindependence of neutral allele frequencies between human populations. We retest the DRD4 exon 3 alleles, and also test two other loci near DRD4 that are associated with NS. We conclude there is an association between migratory distance and DRD4 exon 3 2R and 7R alleles that cannot be accounted for by neutral genetic processes alone. Copyright © 2011 Wiley-Liss, Inc.

Metabolic remodeling of human skeletal myocytes by cocultured adipocytes depends on the lipolytic state of the system.

PubMed

Kovalik, Jean-Paul; Slentz, Dorothy; Stevens, Robert D; Kraus, William E; Houmard, Joseph A; Nicoll, James B; Lea-Currie, Y Renee; Everingham, Karen; Kien, C Lawrence; Buehrer, Benjamin M; Muoio, Deborah M

2011-07-01

Adipocyte infiltration of the musculoskeletal system is well recognized as a hallmark of aging, obesity, and type 2 diabetes. Intermuscular adipocytes might serve as a benign storage site for surplus lipid or play a role in disrupting energy homeostasis as a result of dysregulated lipolysis or secretion of proinflammatory cytokines. This investigation sought to understand the net impact of local adipocytes on skeletal myocyte metabolism. Interactions between these two tissues were modeled using a coculture system composed of primary human adipocytes and human skeletal myotubes derived from lean or obese donors. Metabolic analysis of myocytes was performed after coculture with lipolytically silent or activated adipocytes and included transcript and metabolite profiling along with assessment of substrate selection and insulin action. Cocultured adipocytes increased myotube mRNA expression of genes involved in oxidative metabolism, regardless of the donor and degree of lipolytic activity. Adipocytes in the basal state sequestered free fatty acids, thereby forcing neighboring myotubes to rely more heavily on glucose fuel. Under this condition, insulin action was enhanced in myotubes from lean but not obese donors. In contrast, when exposed to lipolytically active adipocytes, cocultured myotubes shifted substrate use in favor of fatty acids, which was accompanied by intracellular accumulation of triacylglycerol and even-chain acylcarnitines, decreased glucose oxidation, and modest attenuation of insulin signaling. The effects of cocultured adipocytes on myocyte substrate selection and insulin action depended on the metabolic state of the system. These findings are relevant to understanding the metabolic consequences of intermuscular adipogenesis. © 2011 by the American Diabetes Association.

Metabolic Remodeling of Human Skeletal Myocytes by Cocultured Adipocytes Depends on the Lipolytic State of the System

PubMed Central

Kovalik, Jean-Paul; Slentz, Dorothy; Stevens, Robert D.; Kraus, William E.; Houmard, Joseph A.; Nicoll, James B.; Lea-Currie, Y. Renee; Everingham, Karen; Kien, C. Lawrence; Buehrer, Benjamin M.; Muoio, Deborah M.

2011-01-01

OBJECTIVE Adipocyte infiltration of the musculoskeletal system is well recognized as a hallmark of aging, obesity, and type 2 diabetes. Intermuscular adipocytes might serve as a benign storage site for surplus lipid or play a role in disrupting energy homeostasis as a result of dysregulated lipolysis or secretion of proinflammatory cytokines. This investigation sought to understand the net impact of local adipocytes on skeletal myocyte metabolism. RESEARCH DESIGN AND METHODS Interactions between these two tissues were modeled using a coculture system composed of primary human adipocytes and human skeletal myotubes derived from lean or obese donors. Metabolic analysis of myocytes was performed after coculture with lipolytically silent or activated adipocytes and included transcript and metabolite profiling along with assessment of substrate selection and insulin action. RESULTS Cocultured adipocytes increased myotube mRNA expression of genes involved in oxidative metabolism, regardless of the donor and degree of lipolytic activity. Adipocytes in the basal state sequestered free fatty acids, thereby forcing neighboring myotubes to rely more heavily on glucose fuel. Under this condition, insulin action was enhanced in myotubes from lean but not obese donors. In contrast, when exposed to lipolytically active adipocytes, cocultured myotubes shifted substrate use in favor of fatty acids, which was accompanied by intracellular accumulation of triacylglycerol and even-chain acylcarnitines, decreased glucose oxidation, and modest attenuation of insulin signaling. CONCLUSIONS The effects of cocultured adipocytes on myocyte substrate selection and insulin action depended on the metabolic state of the system. These findings are relevant to understanding the metabolic consequences of intermuscular adipogenesis. PMID:21602515

Revisiting the Serotonin-Aggression Relation in Humans: A Meta-analysis

PubMed Central

Duke, Aaron A.; Bègue, Laurent; Bell, Rob; Eisenlohr-Moul, Tory

2013-01-01

The inverse relation between serotonin and human aggression is often portrayed as “reliable,” “strong,” and “well-established” despite decades of conflicting reports and widely recognized methodological limitations. In this systematic review and meta-analysis we evaluate the evidence for and against the serotonin deficiency hypothesis of human aggression across four methods of assessing serotonin: (a) cerebrospinal fluid levels of 5-hydroxyindoleacetic acid (CSF 5-HIAA), (b) acute tryptophan depletion, (c) pharmacological challenge, and (d) endocrine challenge. Results across 175 independent samples and over 6,500 total participants were heterogeneous, but, in aggregate, revealed a small, inverse correlation between central serotonin functioning and aggression, anger, and hostility, r = −.12. Pharmacological challenge studies had the largest mean weighted effect size, r = −.21, and CSF 5-HIAA studies had the smallest, r = −.06, p = .21. Potential methodological and demographic moderators largely failed to account for variability in study outcomes. Notable exceptions included year of publication (effect sizes tended to diminish with time) and self-versus other-reported aggression (other-reported aggression was positively correlated to serotonin functioning). We discuss four possible explanations for the pattern of findings: unreliable measures, ambient correlational noise, an unidentified higher-order interaction, and a selective serotonergic effect. Finally, we provide four recommendations for bringing much needed clarity to this important area of research: acknowledge contradictory findings and avoid selective reporting practices; focus on improving the reliability and validity of serotonin and aggression measures; test for interactions involving personality and/or environmental moderators; and revise the serotonin deficiency hypothesis to account for serotonin’s functional complexity. PMID:23379963

21 CFR 330.5 - Drug categories.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 5 2014-04-01 2014-04-01 false Drug categories. 330.5 Section 330.5 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE OVER-THE-COUNTER (OTC) HUMAN DRUGS WHICH ARE GENERALLY RECOGNIZED AS SAFE AND EFFECTIVE AND NOT...

21 CFR 330.5 - Drug categories.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 5 2012-04-01 2012-04-01 false Drug categories. 330.5 Section 330.5 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE OVER-THE-COUNTER (OTC) HUMAN DRUGS WHICH ARE GENERALLY RECOGNIZED AS SAFE AND EFFECTIVE AND NOT...

21 CFR 330.5 - Drug categories.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 5 2013-04-01 2013-04-01 false Drug categories. 330.5 Section 330.5 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE OVER-THE-COUNTER (OTC) HUMAN DRUGS WHICH ARE GENERALLY RECOGNIZED AS SAFE AND EFFECTIVE AND NOT...

21 CFR 330.5 - Drug categories.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 5 2011-04-01 2011-04-01 false Drug categories. 330.5 Section 330.5 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE OVER-THE-COUNTER (OTC) HUMAN DRUGS WHICH ARE GENERALLY RECOGNIZED AS SAFE AND EFFECTIVE AND NOT...

21 CFR 330.5 - Drug categories.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Drug categories. 330.5 Section 330.5 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE OVER-THE-COUNTER (OTC) HUMAN DRUGS WHICH ARE GENERALLY RECOGNIZED AS SAFE AND EFFECTIVE AND NOT...

Human Dignity Through History.

ERIC Educational Resources Information Center

Satterlie, Arthur L.

A major educational need, as assessed by a committee of teachers, students, and community members, is to recognize acceptance of human dignity as the ultimate value in decision making. This concept provides a basis for the elementary and secondary social studies program. Although the concept of human dignity was promoted with the signing of the…

Stimulus-Dependent Flexibility in Non-Human Auditory Pitch Processing

ERIC Educational Resources Information Center

Bregman, Micah R.; Patel, Aniruddh D.; Gentner, Timothy Q.

2012-01-01

Songbirds and humans share many parallels in vocal learning and auditory sequence processing. However, the two groups differ notably in their abilities to recognize acoustic sequences shifted in absolute pitch (pitch height). Whereas humans maintain accurate recognition of words or melodies over large pitch height changes, songbirds are…

Linking Career Development and Human Resource Planning.

ERIC Educational Resources Information Center

Gutteridge, Thomas G.

When organizations integrate their career development and human resources planning activities into a comprehensive whole, it is the exception rather than the rule. One reason for the frequent dichotomy between career development and human resource planning is the failure to recognize that they are complements rather than synonyms or substitutes.…

Mapping of cat albumin using monoclonal antibodies: identification of determinants common to cat and dog.

PubMed Central

Boutin, Y; Hébert, J; Vrancken, E R; Mourad, W

1989-01-01

Cat and dog albumins from commercial extracts were used to produce monoclonal antibodies (MoAb). Anti-cat albumin MoAb recognized both cat and dog albumin equally, as did anti-dog albumin MoAb; this confirms cross-reactivity between cat and dog. The MoAb were separated into two groups according to their epitopic specificity; they recognized two overlapping epitopes of cat albumin. Furthermore, by competitive inhibition of radio-allergosorbent test (RAST), it was shown that one MoAb group inhibited significantly the binding of human IgE antibodies (from a pool of 13 patients allergic to both cats and dogs) to insolubilized cat or dog extracts. These observations suggest that murine anti-cat or anti-dog MoAb and human IgE antibodies recognize identical or closely related determinants on cat and dog albumin. Images Fig. 1 Fig. 2 PMID:2478325

Using Noninvasive Wearable Computers to Recognize Human Emotions from Physiological Signals

NASA Astrophysics Data System (ADS)

Lisetti, Christine Lætitia; Nasoz, Fatma

2004-12-01

We discuss the strong relationship between affect and cognition and the importance of emotions in multimodal human computer interaction (HCI) and user modeling. We introduce the overall paradigm for our multimodal system that aims at recognizing its users' emotions and at responding to them accordingly depending upon the current context or application. We then describe the design of the emotion elicitation experiment we conducted by collecting, via wearable computers, physiological signals from the autonomic nervous system (galvanic skin response, heart rate, temperature) and mapping them to certain emotions (sadness, anger, fear, surprise, frustration, and amusement). We show the results of three different supervised learning algorithms that categorize these collected signals in terms of emotions, and generalize their learning to recognize emotions from new collections of signals. We finally discuss possible broader impact and potential applications of emotion recognition for multimodal intelligent systems.

Robust selectivity to two-object images in human visual cortex

PubMed Central

Agam, Yigal; Liu, Hesheng; Papanastassiou, Alexander; Buia, Calin; Golby, Alexandra J.; Madsen, Joseph R.; Kreiman, Gabriel

2010-01-01

SUMMARY We can recognize objects in a fraction of a second in spite of the presence of other objects [1–3]. The responses in macaque areas V4 and inferior temporal cortex [4–15] to a neuron’s preferred stimuli are typically suppressed by the addition of a second object within the receptive field (see however [16, 17]). How can this suppression be reconciled with rapid visual recognition in complex scenes? One option is that certain “special categories” are unaffected by other objects [18] but this leaves the problem unsolved for other categories. Another possibility is that serial attentional shifts help ameliorate the problem of distractor objects [19–21]. Yet, psychophysical studies [1–3], scalp recordings [1] and neurophysiological recordings [14, 16, 22–24], suggest that the initial sweep of visual processing contains a significant amount of information. We recorded intracranial field potentials in human visual cortex during presentation of flashes of two-object images. Visual selectivity from temporal cortex during the initial ~200 ms was largely robust to the presence of other objects. We could train linear decoders on the responses to isolated objects and decode information in two-object images. These observations are compatible with parallel, hierarchical and feed-forward theories of rapid visual recognition [25] and may provide a neural substrate to begin to unravel rapid recognition in natural scenes. PMID:20417105

Sol-gel-graphene-based fabric-phase sorptive extraction for cow and human breast milk sample cleanup for screening bisphenol A and residual dental restorative material before analysis by HPLC with diode array detection.

PubMed

Samanidou, Victoria; Filippou, Olga; Marinou, Eirini; Kabir, Abuzar; Furton, Kenneth G

2017-06-01

Fabric-phase sorptive extraction has already been recognized as a simple and green alternative to the conventional sorbent-based sorptive microextraction techniques, using hybrid organic-inorganic sorbent coatings chemically bonded to a flexible fabric surface. Herein, we have investigated the synergistic combination of the advanced material properties offered by sol-gel graphene sorbent and the simplicity of Fabric phase sorptive extraction approach in selectively extracting bisphenol A and residual monomers including bisphenol A glycerolatedimethacrylate, urethane dimethacrylate, and triethylene glycol dimethacrylate derived dental restorative materials from cow and human breast milk samples. Different coatings were evaluated. Final method development employed sol-gel graphene coated media. The main experimental parameters influencing extraction of the compounds, such as sorbent chemistry used, sample loading conditions, elution solvent, sorption stirring time, elution time, impact of protein precipitation, amount of sample, and matrix effect, were investigated and optimized. Absolute recovery values from standard solutions were 50% for bisphenol A, 78% for T triethylene glycol dimethacrylate, 110% for urethane dimethacrylate, and 103% for bisphenol A glycerolatedimethacrylate, while respective absolute recovery values from milk were 30, 52, 104, and 42%. Method validation was performed according to European Decision 657/2002/EC in terms of selectivity, sensitivity, linearity, accuracy, and precision. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Differential interaction of Escherichia coli heat-labile toxin and cholera toxin with pig intestinal brush border glycoproteins depending on their ABH and related blood group antigenic determinants.

PubMed

Balanzino, L E; Barra, J L; Monferran, C G; Cumar, F A

1994-04-01

The ability of glycoproteins from pig intestinal brush border membranes (BBM) to bind cholera toxin (CT) or heat-labile toxins from strains of Escherichia coli isolated from human (LTh) or pig (LTp) intestines was studied. Glycoproteins capable of binding the toxins are also recognized by antibodies or lectins specific for ABO(H) blood group and related antigens. Pigs expressing A, H, or I antigenic determinants were used for comparison. The toxin-binding capacity of a glycoprotein depends on the toxin type and the blood group epitope borne by the glycoprotein. LTh and LTp preferably bound to several blood group A-active glycoproteins rather than H-active glycoproteins. By contrast, CT practically did not recognize either blood group A- or blood group H-active glycoproteins, while glycoproteins from pigs expressing I antigenic determinants were able to interact with LTh, LTp, and CT. LTh, LTp, or CT glycoprotein binding was selectively inhibited by specific lectins or monosaccharides. Affinity purification of the toxin binding brush border glycoproteins on the basis of their blood group reactivity suggests that such glycoproteins are hydrolytic enzymes. BBM from A+ pigs contain about 27 times more LTh binding sites, in addition to those recognized by CT, than an equivalent membrane preparation from H+ pigs. The present findings may help clarify some previous unclear results on LTh binding to intestinal BBM glycoproteins obtained by use of animals not typed by their ABO(H) blood group phenotype.

The Story of Mangrove Depletion: Using Socioscientific Cases to Promote Ocean Literacy

ERIC Educational Resources Information Center

Luther, Rachel A.; Tippins, Deborah J.; Bilbao, Purita P.; Tan, Andrew; Gelvezon, Ruth L.

2013-01-01

The value of mangroves and mangrove ecosystems has not always been recognized. In fact, mangroves were historically regarded largely as wastelands with little or no value. Over time, humans began to recognize the multiple ways in which they could be used, particularly through development, making the mangrove ecosystem vulnerable to destruction and…

Overview of the HFM-181 Symposium Programme, Medical Technology Repurposed to Enhance Human Performance

DTIC Science & Technology

2009-10-01

BIO -INSPIRED HUMAN PERFORMANCE ENHANCEMENT 3.1 Biological performance currently outside of the bounds of the human species HPE opportunities may...strategies to preferentially burn fat in weight reduction (85). 3.2 Bio -inspired opportunities for human performance There are many interesting...solutions to assist human performance Nonmedical applications of bio -inspired engineering and computing technologies are a recognized priority in

Perspectives on global change theory

USDA-ARS?s Scientific Manuscript database

Human-caused global changes in ecological drivers, such as carbon dioxide concentrations, climate, and nitrogen deposition, as well as direct human impacts (land use change, species movements and extinctions, etc.) are increasingly recognized as key to understanding contemporary ecosystem dynamics, ...

5 CFR 9701.501 - Purpose.

Code of Federal Regulations, 2011 CFR

2011-01-01

... Administrative Personnel DEPARTMENT OF HOMELAND SECURITY HUMAN RESOURCES MANAGEMENT SYSTEM (DEPARTMENT OF HOMELAND SECURITY-OFFICE OF PERSONNEL MANAGEMENT) DEPARTMENT OF HOMELAND SECURITY HUMAN RESOURCES... Department's mission foremost in mind. The regulations also recognize the rights of DHS employees to organize...

Parallel structures in human and computer memory

NASA Astrophysics Data System (ADS)

Kanerva, Pentti

1986-08-01

If we think of our experiences as being recorded continuously on film, then human memory can be compared to a film library that is indexed by the contents of the film strips stored in it. Moreover, approximate retrieval cues suffice to retrieve information stored in this library: We recognize a familiar person in a fuzzy photograph or a familiar tune played on a strange instrument. This paper is about how to construct a computer memory that would allow a computer to recognize patterns and to recall sequences the way humans do. Such a memory is remarkably similar in structure to a conventional computer memory and also to the neural circuits in the cortex of the cerebellum of the human brain. The paper concludes that the frame problem of artificial intelligence could be solved by the use of such a memory if we were able to encode information about the world properly.

Unrecognized "AIDS" in Monkeys, 1969-1980: Explanations and Implications.

PubMed

Hammett, Theodore M; Bronson, Roderick T

2016-06-01

AIDS was recognized in humans in 1981 and a simian form was described in the years 1983 to 1985. However, beginning in the late 1960s, outbreaks of opportunistic infections of AIDS were seen in monkeys in the United States. This apparent syndrome went unrecognized at the time. We have assembled those early cases in monkeys and offer reasons why they did not result in earlier recognition of simian or human AIDS, including weaknesses in understanding disease mechanisms, absence of evidence of human retroviruses, and a climate of opinion that devalued investigation of infectious disease and immunologic origins of disease. The "epistemological obstacle" explains important elements of this history in that misconceptions blocked understanding of the dependent relationship among viral infection, immunodeficiency, and opportunistic diseases. Had clearer understanding of the evidence from monkeys allowed human AIDS to be recognized earlier, life-saving prevention and treatment interventions might have been implemented sooner.

A voice region in the monkey brain.

PubMed

Petkov, Christopher I; Kayser, Christoph; Steudel, Thomas; Whittingstall, Kevin; Augath, Mark; Logothetis, Nikos K

2008-03-01

For vocal animals, recognizing species-specific vocalizations is important for survival and social interactions. In humans, a voice region has been identified that is sensitive to human voices and vocalizations. As this region also strongly responds to speech, it is unclear whether it is tightly associated with linguistic processing and is thus unique to humans. Using functional magnetic resonance imaging of macaque monkeys (Old World primates, Macaca mulatta) we discovered a high-level auditory region that prefers species-specific vocalizations over other vocalizations and sounds. This region not only showed sensitivity to the 'voice' of the species, but also to the vocal identify of conspecific individuals. The monkey voice region is located on the superior-temporal plane and belongs to an anterior auditory 'what' pathway. These results establish functional relationships with the human voice region and support the notion that, for different primate species, the anterior temporal regions of the brain are adapted for recognizing communication signals from conspecifics.

Parallel structures in human and computer memory

NASA Technical Reports Server (NTRS)

Kanerva, P.

1986-01-01

If one thinks of our experiences as being recorded continuously on film, then human memory can be compared to a film library that is indexed by the contents of the film strips stored in it. Moreover, approximate retrieval cues suffice to retrieve information stored in this library. One recognizes a familiar person in a fuzzy photograph or a familiar tune played on a strange instrument. A computer memory that would allow a computer to recognize patterns and to recall sequences the way humans do is constructed. Such a memory is remarkably similiar in structure to a conventional computer memory and also to the neural circuits in the cortex of the cerebellum of the human brain. It is concluded that the frame problem of artificial intelligence could be solved by the use of such a memory if one were able to encode information about the world properly.

Unrecognized “AIDS” in Monkeys, 1969–1980: Explanations and Implications

PubMed Central

Bronson, Roderick T.

2016-01-01

AIDS was recognized in humans in 1981 and a simian form was described in the years 1983 to 1985. However, beginning in the late 1960s, outbreaks of opportunistic infections of AIDS were seen in monkeys in the United States. This apparent syndrome went unrecognized at the time. We have assembled those early cases in monkeys and offer reasons why they did not result in earlier recognition of simian or human AIDS, including weaknesses in understanding disease mechanisms, absence of evidence of human retroviruses, and a climate of opinion that devalued investigation of infectious disease and immunologic origins of disease. The “epistemological obstacle” explains important elements of this history in that misconceptions blocked understanding of the dependent relationship among viral infection, immunodeficiency, and opportunistic diseases. Had clearer understanding of the evidence from monkeys allowed human AIDS to be recognized earlier, life-saving prevention and treatment interventions might have been implemented sooner. PMID:27077355

The Intervention Selection Bias: An Underrecognized Confound in Intervention Research

ERIC Educational Resources Information Center

Larzelere, Robert E.; Kuhn, Brett R.; Johnson, Byron

2004-01-01

Selection bias can be the most important threat to internal validity in intervention research, but is often insufficiently recognized and controlled. The bias is illustrated in research on parental interventions (punishment, homework assistance); medical interventions (hospitalization); and psychological interventions for suicide risk, sex…

Cell Context Dependent p53 Genome-Wide Binding Patterns and Enrichment at Repeats

DOE PAGES

Botcheva, Krassimira; McCorkle, Sean R.

2014-11-21

The p53 ability to elicit stress specific and cell type specific responses is well recognized, but how that specificity is established remains to be defined. Whether upon activation p53 binds to its genomic targets in a cell type and stress type dependent manner is still an open question. Here we show that the p53 binding to the human genome is selective and cell context-dependent. We mapped the genomic binding sites for the endogenous wild type p53 protein in the human cancer cell line HCT116 and compared them to those we previously determined in the normal cell line IMR90. We reportmore » distinct p53 genome-wide binding landscapes in two different cell lines, analyzed under the same treatment and experimental conditions, using the same ChIP-seq approach. This is evidence for cell context dependent p53 genomic binding. The observed differences affect the p53 binding sites distribution with respect to major genomic and epigenomic elements (promoter regions, CpG islands and repeats). We correlated the high-confidence p53 ChIP-seq peaks positions with the annotated human repeats (UCSC Human Genome Browser) and observed both common and cell line specific trends. In HCT116, the p53 binding was specifically enriched at LINE repeats, compared to IMR90 cells. The p53 genome-wide binding patterns in HCT116 and IMR90 likely reflect the different epigenetic landscapes in these two cell lines, resulting from cancer-associated changes (accumulated in HCT116) superimposed on tissue specific differences (HCT116 has epithelial, while IMR90 has mesenchymal origin). In conclusion, our data support the model for p53 binding to the human genome in a highly selective manner, mobilizing distinct sets of genes, contributing to distinct pathways.« less

Fate and transport of some selected PhACs in a river receiving a high load of treated sewage

NASA Astrophysics Data System (ADS)

Bendz, D.; Ginn, T. R.; Paxeus, N.

2003-04-01

Pharmaceutical active compounds (PhACs) have lately been acknowledged to constitute a risk for humans and for the terrestrial and aquatic environment. Human and veterinary applications are the main sources of PhACs in the environment and the major pathway are excretion and discharge to the environment. Sewage treatment plants (STPs) play a crucial role for the introduction of the human PhACs in the environment through its removal efficiency and by separating these compounds into two exposure pathways associated with the aquatic and the solid (sludge) phase, respectively. Actually, STPs are recognized as being the main point discharge sources of human PhACs to the aquatic environment. In this study the fate and transport of a selected human PhACs belonging to different therapeutic classes (NSAIDs- non-steroidal antiinflamatory drugs, lipid regulators, antiepileptics, antibiotics and &beta-blockers) are investigated in a small river in the very south of Sweden receiving a high load of treated wastewater. In addition to the PhACs, triclosan (commonly used biocide) was included in this study. Water samples were taken of incoming and outgoing wastewater from the treatment plant, at the effluent in the river, and along the river up to 8 kilometers downstream were the river flows into the sea. After enrichment by solid-phase extraction the compounds were analyzed using GC-MS (methylated derivatives) or LC-MS/MS. In addition to the target compounds a screening analysis of the extracts revealed the presence of other wastewater related pollutants (caffeine, flame retardants, antioxidants). Several of the investigated substances demonstrate a surprising persistence in the aquatic environment. This emphasizes the need for a broader view on the concept of persistence by taking into account the recharge/loading rate in addition to removal mechanisms; transformation, volatility and physical sequestration by solids and the influence of different environmental media (Soil organic matter, mineralogy, macroscopic physical properties etc) in various hydrological systems.

Phenotype diffusion and one health: A proposed framework for investigating the plurality of obesity epidemics across many species.

PubMed

Voss, J D; Goodson, M S; Leon, J C

2018-05-01

We propose the idea of "phenotype diffusion," which is a rapid convergence of an observed trait in some human and animal populations. The words phenotype and diffusion both imply observations independent of mechanism as phenotypes are observed traits with multiple possible genetic mechanisms and diffusion is an observed state of being widely distributed. Recognizing shared changes in phenotype in multiple species does not by itself reveal a particular mechanism such as a shared exposure, shared adaptive need, particular stochastic process or a transmission pathway. Instead, identifying phenotype diffusion suggests the mechanism should be explored to help illuminate the ways human and animal health are connected and new opportunities for optimizing these links. Using the plurality of obesity epidemics across multiple species as a prototype for shared changes in phenotype, the goal of this review was to explore eco-evolutionary theories that could inform further investigation. First, evolutionary changes described by hologenome evolution, pawnobe evolution, transposable element (TE) thrust and the drifty gene hypothesis will be discussed within the context of the selection asymmetries among human and animal populations. Secondly, the ecology of common source exposures (bovine milk, xenohormesis and "obesogens"), niche evolution and the hygiene hypothesis will be summarized. Finally, we synthesize these considerations. For example, many agricultural breeds have been aggressively selected for weight gain, microbiota (e.g., adenovirus 36, toxoplasmosis) associated with (or infecting) these breeds cause experimental weight gain in other animals, and these same microbes are associated with human obesity. We propose applications of phenotype diffusion could include zoonotic biosurveillance, biocontainment, antibiotic stewardship and environmental priorities. The One Health field is focused on the connections between the health of humans, animals and the environment, and so identification of phenotype diffusion is highly relevant for practitioners (public health officials, physicians and veterinarians) in this field. Published 2018. This article is a U.S. Government work and is in the public domain in the USA.

Selective bispecific T cell recruiting antibody and antitumor activity of adoptive T cell transfer.

PubMed

Kobold, Sebastian; Steffen, Julius; Chaloupka, Michael; Grassmann, Simon; Henkel, Jonas; Castoldi, Raffaella; Zeng, Yi; Chmielewski, Markus; Schmollinger, Jan C; Schnurr, Max; Rothenfußer, Simon; Schendel, Dolores J; Abken, Hinrich; Sustmann, Claudio; Niederfellner, Gerhard; Klein, Christian; Bourquin, Carole; Endres, Stefan

2015-01-01

One bottleneck for adoptive T cell therapy (ACT) is recruitment of T cells into tumors. We hypothesized that combining tumor-specific T cells, modified with a marker antigen and a bispecific antibody (BiAb) that selectively recognizes transduced T cells and tumor cells would improve T cell recruitment to tumors and enhance therapeutic efficacy. SV40 T antigen-specific T cells from T cell receptor (TCR)-I-transgenic mice were transduced with a truncated human epidermal growth factor receptor (EGFR) as a marker protein. Targeting and killing by combined ACT and anti-EGFR-anti-EpCAM BiAb therapy was analyzed in C57Bl/6 mice (n = six to 12 per group) carrying subcutaneous tumors of the murine gastric cancer cell line GC8 (SV40(+) and EpCAM(+)). Anti-EGFR x anti-c-Met BiAb was used for targeting of human tumor-specific T cells to c-Met(+) human tumor cell lines. Differences between experimental conditions were analyzed using the Student's t test, and differences in tumor growth with two-way analysis of variance. Overall survival was analyzed by log-rank test. All statistical tests were two-sided. The BiAb linked EGFR-transduced T cells to tumor cells and enhanced tumor cell lysis. In vivo, the combination of ACT and Biab produced increased T cell infiltration of tumors, retarded tumor growth, and prolonged survival compared with ACT with a control antibody (median survival 95 vs 75 days, P < .001). In human cells, this strategy enhanced recruitment of human EGFR-transduced T cells to immobilized c-Met and recognition of tyrosinase(+) melanoma cells by TCR-, as well as of CEA(+) colon cancer cells by chimeric antigen receptor (CAR)-modified T cells. BiAb recruitment of tumor-specific T cells transduced with a marker antigen to tumor cells may enhance efficacy of ACT. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

The natural antibody repertoire of sharks and humans recognizes the potential universe of antigens.

PubMed

Adelman, Miranda K; Schluter, Samuel F; Marchalonis, John J

2004-02-01

In ancestral sharks, a rapid emergence in the evolution of the immune system occurred, giving jawed-vertebrates the necessary components for the combinatorial immune response (CIR). To compare the natural antibody (NAb) repertoires of the most divergent vertebrates with the capacity to produce antibodies, we isolated NAbs to the same set of antigens by affinity chromatography from two species of Carcharhine sharks and from human polyclonal IgG and IgM antibody preparations. The activities of the affinity-purified anti-T-cell receptor (anti-TCR) NAbs were compared with those of monoclonal anti-TCR NAbs that were generated from a systemic lupus erythematosus patient. We report that sharks and humans, representing the evolutionary extremes of vertebrate species sharing the CIR, have NAbs to human TCRs, Igs, the human senescent cell antigen, and to numerous retroviral antigens, indicating that essential features of the combinatorial repertoire and the capacity to recognize the potential universe of antigens is shared among all jawed-vertebrates.

Analysis of Receptor for Vibrio cholerae El Tor Hemolysin with a Monoclonal Antibody That Recognizes Glycophorin B of Human Erythrocyte Membrane

PubMed Central

Zhang, Dongyan; Takahashi, Junko; Seno, Taiko; Tani, Yoshihiko; Honda, Takeshi

1999-01-01

El Tor hemolysin (ETH), a pore-forming toxin secreted by Vibrio cholerae O1 biotype El Tor and most Vibrio cholerae non-O1 isolates, is able to lyse erythrocytes and other mammalian cells. To study the receptor for this toxin or the related molecule(s) on erythrocyte, we first isolated a monoclonal antibody, B1, against human erythrocyte membrane, which not only blocks the binding of ETH to human erythrocyte but also inhibits the hemolytic activity of ETH. Biochemical characterization and immunoblotting revealed that this antibody recognized an epitope on the extracellular domain of glycophorin B, a sialoglycoprotein of erythrocyte membrane. Erythrocytes lacking glycophorin B but not glycophorin A were less sensitive to the toxin than were normal human erythrocytes. These results indicate that glycophorin B is a receptor for ETH or at least an associated molecule of the receptor for ETH on human erythrocytes. PMID:10496913

Dogs recognize dog and human emotions.

PubMed

Albuquerque, Natalia; Guo, Kun; Wilkinson, Anna; Savalli, Carine; Otta, Emma; Mills, Daniel

2016-01-01

The perception of emotional expressions allows animals to evaluate the social intentions and motivations of each other. This usually takes place within species; however, in the case of domestic dogs, it might be advantageous to recognize the emotions of humans as well as other dogs. In this sense, the combination of visual and auditory cues to categorize others' emotions facilitates the information processing and indicates high-level cognitive representations. Using a cross-modal preferential looking paradigm, we presented dogs with either human or dog faces with different emotional valences (happy/playful versus angry/aggressive) paired with a single vocalization from the same individual with either a positive or negative valence or Brownian noise. Dogs looked significantly longer at the face whose expression was congruent to the valence of vocalization, for both conspecifics and heterospecifics, an ability previously known only in humans. These results demonstrate that dogs can extract and integrate bimodal sensory emotional information, and discriminate between positive and negative emotions from both humans and dogs. © 2016 The Author(s).

Research of Daily Conversation Transmitting System Based on Mouth Part Pattern Recognition

NASA Astrophysics Data System (ADS)

Watanabe, Mutsumi; Nishi, Natsuko

The authors are developing a vision-based intension transfer technique by recognizing user’s face expressions and movements, to help free and convenient communications with aged or disabled persons who find difficulties in talking, discriminating small character prints and operating keyboards by hands and fingers. In this paper we report a prototype system, where layered daily conversations are successively selected by recognizing the transition in shape of user’s mouth parts using camera image sequences settled in front of the user. Four mouth part patterns are used in the system. A method that automatically recognizes these patterns by analyzing the intensity histogram data around the mouth region is newly developed. The confirmation of a selection on the way is executed by detecting the open and shut movements of mouth through the temporal change in intensity histogram data. The method has been installed in a desktop PC by VC++ programs. Experimental results of mouth shape pattern recognition by twenty-five persons have shown the effectiveness of the method.

Monoclonal antibodies with group specificity toward sulfonamides: selection of hapten and antibody selectivity.

PubMed

Wang, Zhanhui; Beier, Ross C; Sheng, Yajie; Zhang, Suxia; Jiang, Wenxiao; Wang, Zhaopeng; Wang, Jin; Shen, Jianzhong

2013-05-01

Immunoassays based on the current available antibodies for large multi-sulfonamide screening programs have suffered from high selectivity for individual sulfonamides and a wide range of selectivities for different sulfonamides. In this study, five synthesized haptens, HS, BS, CS, SA10, and TS and two sulfonamides, SG and SMX were used as haptens, which may or may not contain a ring structure at the N1 position of the sulfonamides, were selected to evaluate the effectiveness for producing group-specific monoclonal antibodies (MAbs). Mice immunized with three different two-ring haptens were used for hybridoma production, which resulted in three unique MAbs recognizing 10, 13, and 15 sulfonamides showing 50 % inhibition (IC50) at concentrations below 100 ng mL(-1). MAb 4D11 derived from one novel immunizing hapten could recognize 12 sulfonamides with IC50 values ranging from 1.2 to 12.4 ng mL(-1), almost within 1 order of magnitude. These produced MAbs show lower IC50 values in addition to significantly improved group specificity compared with previously generated MAbs. This study clearly indicates that the careful selection of the immunizing hapten has an important effect on the specificity of the generated antibodies.

4F2 monoclonal antibody recognizes a surface antigen on spread human fibroblasts of embryonic but not of adult origin

PubMed Central

1984-01-01

The 4F2 monoclonal antibody (mAb) has been shown to recognize a 120- kilodalton glycoprotein expressed on the cell surface of human peripheral blood monocytes, activated (but not resting) T or B cells, and T and B lymphoblastoid cell lines. In this report we show that 4F2 mAb specifically binds to the surface of adherent human embryonic fibroblasts but fails to bind to normal adult fibroblasts. Moreover, 4F2 antigen was expressed on sarcoma-derived or SV40-transformed adult fibroblastic cells. Finally, addition of 4F2 mAb inhibited the growth of cultured HT-1080 fibrosarcoma cell line, but had no inhibitory effect on various embryonic and adult normal or transformed fibroblasts. PMID:6538202

Finding aroma clues in the human breath to diagnose diseases

Treesearch

A. Dan Wilson

2016-01-01

History of human odor analysis in disease diagnosis The use of the sense of smell as an indicator of human disease probably originated with Hippocrates (circa 400 BC). Early medical practitioners recognized that the presence of human diseases changed the odors released from the body and breath. Physicians once relied heavily on their sense of smell to provide useful...

Selection of Norway spruce somatic embryos by computer vision

NASA Astrophysics Data System (ADS)

Hamalainen, Jari J.; Jokinen, Kari J.

1993-05-01

A computer vision system was developed for the classification of plant somatic embryos. The embryos are in a Petri dish that is transferred with constant speed and they are recognized as they pass a line scan camera. A classification algorithm needs to be installed for every plant species. This paper describes an algorithm for the recognition of Norway spruce (Picea abies) embryos. A short review of conifer micropropagation by somatic embryogenesis is also given. The recognition algorithm is based on features calculated from the boundary of the object. Only part of the boundary corresponding to the developing cotyledons (2 - 15) and the straight sides of the embryo are used for recognition. An index of the length of the cotyledons describes the developmental stage of the embryo. The testing set for classifier performance consisted of 118 embryos and 478 nonembryos. With the classification tolerances chosen 69% of the objects classified as embryos by a human classifier were selected and 31$% rejected. Less than 1% of the nonembryos were classified as embryos. The basic features developed can probably be easily adapted for the recognition of other conifer somatic embryos.

Development of a carbazole-based fluorescence probe for G-quadruplex DNA: The importance of side-group effect on binding specificity.

PubMed

Wang, Ming-Qi; Ren, Gui-Ying; Zhao, Shuang; Lian, Guang-Chang; Chen, Ting-Ting; Ci, Yang; Li, Hong-Yao

2018-06-15

G-quadruplex DNAs are highly prevalent in the human genome and involved in many important biological processes. However, many aspects of their biological mechanism and significance still need to be elucidated. Therefore, the development of fluorescent probes for G-quadruplex detection is important for the basic research. We report here on the development of small molecular dyes designed on the basis of carbazole scaffold by introducing styrene-like substituents at its 9-position, for the purpose of G-quadruplex recognition. Results revealed that the side group on the carbazole scaffold was very important for their ability to selectively recognize G-quadruplex DNA structures. 1a with the pyridine side group displayed excellent fluorescence signal turn-on property for the specific discrimination of G-quadruplex DNAs against other nucleic acids. The characteristics of 1a were further investigated with UV-vis spectrophotometry, fluorescence, circular dichroism, FID assay and molecular docking to validate the selectivity, sensitivity and detailed binding mode toward G-quadruplex DNAs. Copyright © 2018 Elsevier B.V. All rights reserved.

A simple rule for the evolution of cooperation on graphs and social networks.

PubMed

Ohtsuki, Hisashi; Hauert, Christoph; Lieberman, Erez; Nowak, Martin A

2006-05-25

A fundamental aspect of all biological systems is cooperation. Cooperative interactions are required for many levels of biological organization ranging from single cells to groups of animals. Human society is based to a large extent on mechanisms that promote cooperation. It is well known that in unstructured populations, natural selection favours defectors over cooperators. There is much current interest, however, in studying evolutionary games in structured populations and on graphs. These efforts recognize the fact that who-meets-whom is not random, but determined by spatial relationships or social networks. Here we describe a surprisingly simple rule that is a good approximation for all graphs that we have analysed, including cycles, spatial lattices, random regular graphs, random graphs and scale-free networks: natural selection favours cooperation, if the benefit of the altruistic act, b, divided by the cost, c, exceeds the average number of neighbours, k, which means b/c > k. In this case, cooperation can evolve as a consequence of 'social viscosity' even in the absence of reputation effects or strategic complexity.

Effect of (E)-5-(2-bromovinyl)-2'-deoxyuridine on several parameters of Epstein-Barr virus infection.

PubMed

Zhang, Z X; Liu, Y X; Chen, H C; Allaudeen, H S; De Clercq, E

1984-01-01

The selective and potent anti-herpesvirus drug, (E)-5-(2-bromovinyl)-2'-deoxyuridine (BVdU), has been examined for its inhibitory effects on several parameters of Epstein-Barr virus (EBV) infection in the lymphoblastoid cell lines Raji, P3HR-1, B-95-8 and P3 hybrid cells (a human embryo oropharyngeal cell line fused with a nasopharyngeal carcinoma cell line). At a dosage of 0.03 to 0.1 mM, BVdU caused a marked inhibition of (i) spontaneous viral capsid antigen (VCA) expression in B-95-8 and P3 hybrid cells, (ii) VCA expression and DNA synthesis in B-95-8 cells induced with croton oil and n-butyrate, (iii) early antigen (EA) expression and DNA synthesis in Raji cells superinfected with EBV, and (iv) VCA expression and DNA synthesis in B-95-8 cells superinfected with EBV. In its inhibitory effects on these various parameters of EBV infection, BVdU appears to be comparable to acyclovir [9-(2-hydroxyethoxymethyl)guanine], another selective anti-herpesvirus drug which has been previously recognized as an effective inhibitor of EBV replication.

Perception of animacy in dogs and humans.

PubMed

Abdai, Judit; Ferdinandy, Bence; Terencio, Cristina Baño; Pogány, Ákos; Miklósi, Ádám

2017-06-01

Humans have a tendency to perceive inanimate objects as animate based on simple motion cues. Although animacy is considered as a complex cognitive property, this recognition seems to be spontaneous. Researchers have found that young human infants discriminate between dependent and independent movement patterns. However, quick visual perception of animate entities may be crucial to non-human species as well. Based on general mammalian homology, dogs may possess similar skills to humans. Here, we investigated whether dogs and humans discriminate similarly between dependent and independent motion patterns performed by geometric shapes. We projected a side-by-side video display of the two patterns and measured looking times towards each side, in two trials. We found that in Trial 1, both dogs and humans were equally interested in the two patterns, but in Trial 2 of both species, looking times towards the dependent pattern decreased, whereas they increased towards the independent pattern. We argue that dogs and humans spontaneously recognized the specific pattern and habituated to it rapidly, but continued to show interest in the 'puzzling' pattern. This suggests that both species tend to recognize inanimate agents as animate relying solely on their motions. © 2017 The Author(s).

Face-selective neurons maintain consistent visual responses across months

PubMed Central

McMahon, David B. T.; Jones, Adam P.; Bondar, Igor V.; Leopold, David A.

2014-01-01

Face perception in both humans and monkeys is thought to depend on neurons clustered in discrete, specialized brain regions. Because primates are frequently called upon to recognize and remember new individuals, the neuronal representation of faces in the brain might be expected to change over time. The functional properties of neurons in behaving animals are typically assessed over time periods ranging from minutes to hours, which amounts to a snapshot compared to a lifespan of a neuron. It therefore remains unclear how neuronal properties observed on a given day predict that same neuron's activity months or years later. Here we show that the macaque inferotemporal cortex contains face-selective cells that show virtually no change in their patterns of visual responses over time periods as long as one year. Using chronically implanted microwire electrodes guided by functional MRI targeting, we obtained distinct profiles of selectivity for face and nonface stimuli that served as fingerprints for individual neurons in the anterior fundus (AF) face patch within the superior temporal sulcus. Longitudinal tracking over a series of daily recording sessions revealed that face-selective neurons maintain consistent visual response profiles across months-long time spans despite the influence of ongoing daily experience. We propose that neurons in the AF face patch are specialized for aspects of face perception that demand stability as opposed to plasticity. PMID:24799679

Face-selective neurons maintain consistent visual responses across months.

PubMed

McMahon, David B T; Jones, Adam P; Bondar, Igor V; Leopold, David A

2014-06-03

Face perception in both humans and monkeys is thought to depend on neurons clustered in discrete, specialized brain regions. Because primates are frequently called upon to recognize and remember new individuals, the neuronal representation of faces in the brain might be expected to change over time. The functional properties of neurons in behaving animals are typically assessed over time periods ranging from minutes to hours, which amounts to a snapshot compared to a lifespan of a neuron. It therefore remains unclear how neuronal properties observed on a given day predict that same neuron's activity months or years later. Here we show that the macaque inferotemporal cortex contains face-selective cells that show virtually no change in their patterns of visual responses over time periods as long as one year. Using chronically implanted microwire electrodes guided by functional MRI targeting, we obtained distinct profiles of selectivity for face and nonface stimuli that served as fingerprints for individual neurons in the anterior fundus (AF) face patch within the superior temporal sulcus. Longitudinal tracking over a series of daily recording sessions revealed that face-selective neurons maintain consistent visual response profiles across months-long time spans despite the influence of ongoing daily experience. We propose that neurons in the AF face patch are specialized for aspects of face perception that demand stability as opposed to plasticity.

Molecular Analysis of the Human Autoantibody Response to α-Fodrin in Sjögren’s Syndrome Reveals Novel Apoptosis-Induced Specificity

PubMed Central

Maruyama, Toshiaki; Saito, Ichiro; Hayashi, Yoshio; Kompfner, Elizabeth; Fox, Robert I.; Burton, Dennis R.; Ditzel, Henrik J.

2004-01-01

Lymphocyte infiltration of salivary and lacrimal glands leading to diminished secretion and gland destruction as a result of apoptosis is thought to be pivotal in the pathogenesis of Sjögren’s syndrome (SS). The cytoskeletal protein α-fodrin is cleaved during this apoptotic process, and a strong antibody (Ab) response is elicited to a 120-kd fragment of cleaved α-fodrin in the majority of SS patients, but generally not in other diseases in which apoptosis also occurs. Little is known about the anti-α-fodrin autoantibody response on a molecular level. To address this issue, IgG phage display libraries were generated from the bone marrow of two SS donors and a panel of anti-α-fodrin IgGs was isolated by selection on α-fodrin immunoblots. All of the human monoclonal Abs (hmAbs) reacted with a 150-kd fragment and not with the 120-kd fragment or intact α-fodrin, indicating that the epitope recognized became exposed after α-fodrin cleavage. Analysis of a large panel of SS patients (defined by the strict San Diego diagnostic criteria) showed that 25% of SS sera exhibited this 150-kd α-fodrin specificity. The hmAbs stained human cultured salivary acinar cells and the staining was redistributed to surface blebs during apoptosis. They also stained inflamed acinar/ductal epithelial cells in SS salivary tissue biopsies, and only partially co-localized with monoclonal Abs recognizing the full-length α-fodrin. Our study shows that in SS patients, neoepitopes on the 150-kd cleaved product of α-fodrin become exposed to the immune system, frequently eliciting anti-150-kd α-fodrin Abs in addition to the previously reported anti-120-kd Abs. The anti-150-kd α-fodrin hmAbs may serve as valuable reagents for the study of SS pathogenesis and diagnostic analyses of SS salivary gland tissue. PMID:15215161

Unpacking rights in indigenous African societies: indigenous culture and the question of sexual and reproductive rights in Africa

PubMed Central

2011-01-01

Background Modern declarations on human rights have often proceeded without reference to the cultural content of rights, the existence of rights in African indigenous backgrounds, and the embodiment of certain key rights in the community itself. This paper is an attempt at developing an ‘inventory’ of rights in African cultures as a prelude to the generation both of a holistic theory of rights as well as a research agenda that can recognize the multifaceted nature of rights. Methods We use an interpretive ethnographic approach built on three sources of data: 1) our continuing ethnographic work among two distinct ethnic groups in southeastern Nigeria – the Ubang and the Igbo; 2) informal conversational interviews with individuals from a range of African countries; and 3) a review of relevant literature based on African cultures which provides a context for some of the issues we raise. Results An examination of selected indigenous rights, entitlements, or privileges among the Ubang and Igbo illustrates indigenous culture as a key, but often neglected, axis of rights, as a critical framework for understanding human relationships with rights, and as a resource for, and challenge to, contemporary programmatic efforts focusing on universalized notions of rights. Understanding or interpreting rights in African settings within the framework defined by contemporary human rights discourse poses steep challenges to making progress in the realization of sexual and reproductive rights. Conclusions Despite the potential dangers of privileging group rights over individual rights, when important rights are vested in the community; rights, entitlements, and privileges can also be recognized through community experiences, and realized through engagement with communities. Building on communal conceptualizations of rights in order to realize an even wider range of rights remains a largely unexplored strategy which holds promise for the achievement of sexual and reproductive health rights. PMID:22375959

Fat, demented and stupid: An unrecognized legacy of pediatric urology?

PubMed

Cooper, Christopher S

2017-08-01

The human body is an unfathomably intricate structure consisting of many connected and intertwined systems. This makes it impossible for therapeutic interventions to selectively target only one physiologic system without some impact or side effects on all the other systems. The resiliency of the human body modifies and disguises side effects, some of which may be undetectable for years and not apparent without scientific investigation. Pediatric urologists employ relatively few medications for the common conditions they treat and in general these consist of antibiotics, anticholinergics, and anesthetics. Although harm from early side effects is well recognized, recent medical literature suggests there may be other side effects of these common interventions that aren't as well recognized. Antibiotics have been added to livestock feed as growth promoters for three-quarters of a century. Antibiotics alter the microbiota of the intestinal tract and these alterations have been demonstrated to impact growth, metabolism, and the risk of obesity in animals and humans. To date, the long-term impact of daily antibiotic prophylaxis in children with such pediatric urology conditions as vesicoureteral reflux or prenatal hydronephrosis have not been published. Similarly, there are no studies assessing long-term effects of anticholinergic use on cognition in children despite research demonstrating an increased risk of dementia in adults using anticholinergics. Research in animals and children recently led the FDA to issue a warning regarding the risk of lengthy use of general anesthesia on cognitive development in children. This review raises the possibility that antibiotics in children may alter growth, anticholinergics may increase their risk of dementia later in life, and anesthetics may impair their cognitive development. The possibility of such an unrecognized legacy from current therapeutic interventions should give all physicians, including pediatric urologists, pause for consideration before electing any intervention, no matter how routine or currently well accepted. Copyright © 2017 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.

Perceptual learning and human expertise

NASA Astrophysics Data System (ADS)

Kellman, Philip J.; Garrigan, Patrick

2009-06-01

We consider perceptual learning: experience-induced changes in the way perceivers extract information. Often neglected in scientific accounts of learning and in instruction, perceptual learning is a fundamental contributor to human expertise and is crucial in domains where humans show remarkable levels of attainment, such as language, chess, music, and mathematics. In Section 2, we give a brief history and discuss the relation of perceptual learning to other forms of learning. We consider in Section 3 several specific phenomena, illustrating the scope and characteristics of perceptual learning, including both discovery and fluency effects. We describe abstract perceptual learning, in which structural relationships are discovered and recognized in novel instances that do not share constituent elements or basic features. In Section 4, we consider primary concepts that have been used to explain and model perceptual learning, including receptive field change, selection, and relational recoding. In Section 5, we consider the scope of perceptual learning, contrasting recent research, focused on simple sensory discriminations, with earlier work that emphasized extraction of invariance from varied instances in more complex tasks. Contrary to some recent views, we argue that perceptual learning should not be confined to changes in early sensory analyzers. Phenomena at various levels, we suggest, can be unified by models that emphasize discovery and selection of relevant information. In a final section, we consider the potential role of perceptual learning in educational settings. Most instruction emphasizes facts and procedures that can be verbalized, whereas expertise depends heavily on implicit pattern recognition and selective extraction skills acquired through perceptual learning. We consider reasons why perceptual learning has not been systematically addressed in traditional instruction, and we describe recent successful efforts to create a technology of perceptual learning in areas such as aviation, mathematics, and medicine. Research in perceptual learning promises to advance scientific accounts of learning, and perceptual learning technology may offer similar promise in improving education.

Highly sensitive and selective lateral flow immunoassay based on magnetic nanoparticles for quantitative detection of carcinoembryonic antigen.

PubMed

Liu, Fangming; Zhang, Honglian; Wu, Zhenhua; Dong, Haidao; Zhou, Lin; Yang, Dawei; Ge, Yuqing; Jia, Chunping; Liu, Huiying; Jin, Qinghui; Zhao, Jianlong; Zhang, Qiqing; Mao, Hongju

2016-12-01

Carcinoembryonic antigen (CEA) is an important biomarker in cancer diagnosis. Here, we present an efficient, selective lateral-flow immunoassay (LFIA) based on magnetic nanoparticles (MNPs) for in situ sensitive and accurate point-of-care detection of CEA. Signal amplification mechanism involved linking of detection MNPs with signal MNPs through biotin-modified single-stranded DNA (ssDNA) and streptavidin. To verify the effectiveness of this modified LFIA system, the sensitivity and specificity were evaluated. Sensitivity evaluation showed a broad detection range of 0.25-1000ng/ml for CEA protein by the modified LFIA, and the limit of detection (LOD) of the modified LFIA was 0.25ng/ml, thus producing significant increase in detection threshold compared with the traditional LFIA. The modified LFIA could selectively recognize CEA in presence of several interfering proteins. In addition, this newly developed assay was applied for quantitative detection of CEA in human serum specimens collected from 10 randomly selected patients. The modified LFIA system detected minimum 0.27ng/ml of CEA concentration in serum samples. The results were consistent with the clinical data obtained using commercial electrochemiluminescence immunoassay (ECLIA) (p<0.01). In conclusion, the MNPs based LFIA system not only demonstrated enhanced signal to noise ratio, it also detected CEA with higher sensitivity and selectivity, and thus has great potential to be commercially applied as a sensitive tumor marker filtration system. Copyright © 2016 Elsevier B.V. All rights reserved.

Applying a deep learning based CAD scheme to segment and quantify visceral and subcutaneous fat areas from CT images

NASA Astrophysics Data System (ADS)

Wang, Yunzhi; Qiu, Yuchen; Thai, Theresa; Moore, Kathleen; Liu, Hong; Zheng, Bin

2017-03-01

Abdominal obesity is strongly associated with a number of diseases and accurately assessment of subtypes of adipose tissue volume plays a significant role in predicting disease risk, diagnosis and prognosis. The objective of this study is to develop and evaluate a new computer-aided detection (CAD) scheme based on deep learning models to automatically segment subcutaneous fat areas (SFA) and visceral (VFA) fat areas depicting on CT images. A dataset involving CT images from 40 patients were retrospectively collected and equally divided into two independent groups (i.e. training and testing group). The new CAD scheme consisted of two sequential convolutional neural networks (CNNs) namely, Selection-CNN and Segmentation-CNN. Selection-CNN was trained using 2,240 CT slices to automatically select CT slices belonging to abdomen areas and SegmentationCNN was trained using 84,000 fat-pixel patches to classify fat-pixels as belonging to SFA or VFA. Then, data from the testing group was used to evaluate the performance of the optimized CAD scheme. Comparing to manually labelled results, the classification accuracy of CT slices selection generated by Selection-CNN yielded 95.8%, while the accuracy of fat pixel segmentation using Segmentation-CNN yielded 96.8%. Therefore, this study demonstrated the feasibility of using deep learning based CAD scheme to recognize human abdominal section from CT scans and segment SFA and VFA from CT slices with high agreement compared with subjective segmentation results.

Trade-off between curvature tuning and position invariance in visual area V4

PubMed Central

Sharpee, Tatyana O.; Kouh, Minjoon; Reynolds, John H.

2013-01-01

Humans can rapidly recognize a multitude of objects despite differences in their appearance. The neural mechanisms that endow high-level sensory neurons with both selectivity to complex stimulus features and “tolerance” or invariance to identity-preserving transformations, such as spatial translation, remain poorly understood. Previous studies have demonstrated that both tolerance and selectivity to conjunctions of features are increased at successive stages of the ventral visual stream that mediates visual recognition. Within a given area, such as visual area V4 or the inferotemporal cortex, tolerance has been found to be inversely related to the sparseness of neural responses, which in turn was positively correlated with conjunction selectivity. However, the direct relationship between tolerance and conjunction selectivity has been difficult to establish, with different studies reporting either an inverse or no significant relationship. To resolve this, we measured V4 responses to natural scenes, and using recently developed statistical techniques, we estimated both the relevant stimulus features and the range of translation invariance for each neuron. Focusing the analysis on tuning to curvature, a tractable example of conjunction selectivity, we found that neurons that were tuned to more curved contours had smaller ranges of position invariance and produced sparser responses to natural stimuli. These trade-offs provide empirical support for recent theories of how the visual system estimates 3D shapes from shading and texture flows, as well as the tiling hypothesis of the visual space for different curvature values. PMID:23798444

Functional Glycomic Analysis of Human Milk Glycans Reveals the Presence of Virus Receptors and Embryonic Stem Cell Biomarkers*

PubMed Central

Yu, Ying; Mishra, Shreya; Song, Xuezheng; Lasanajak, Yi; Bradley, Konrad C.; Tappert, Mary M.; Air, Gillian M.; Steinhauer, David A.; Halder, Sujata; Cotmore, Susan; Tattersall, Peter; Agbandje-McKenna, Mavis; Cummings, Richard D.; Smith, David F.

2012-01-01

Human milk contains a large diversity of free glycans beyond lactose, but their functions are not well understood. To explore their functional recognition, here we describe a shotgun glycan microarray prepared from isolated human milk glycans (HMGs), and our studies on their recognition by viruses, antibodies, and glycan-binding proteins (GBPs), including lectins. The total neutral and sialylated HMGs were derivatized with a bifunctional fluorescent tag, separated by multidimensional HPLC, and archived in a tagged glycan library, which was then used to print a shotgun glycan microarray (SGM). This SGM was first interrogated with well defined GBPs and antibodies. These data demonstrated both the utility of the array and provided preliminary structural information (metadata) about this complex glycome. Anti-TRA-1 antibodies that recognize human pluripotent stem cells specifically recognized several HMGs that were then further structurally defined as novel epitopes for these antibodies. Human influenza viruses and Parvovirus Minute Viruses of Mice also specifically recognized several HMGs. For glycan sequencing, we used a novel approach termed metadata-assisted glycan sequencing (MAGS), in which we combine information from analyses of glycans by mass spectrometry with glycan interactions with defined GBPs and antibodies before and after exoglycosidase treatments on the microarray. Together, these results provide novel insights into diverse recognition functions of HMGs and show the utility of the SGM approach and MAGS as resources for defining novel glycan recognition by GBPs, antibodies, and pathogens. PMID:23115247

Artificial-epitope mapping for CK-MB assay.

PubMed

Tai, Dar-Fu; Ho, Yi-Fang; Wu, Cheng-Hsin; Lin, Tzu-Chieh; Lu, Kuo-Hao; Lin, Kun-Shian

2011-06-07

A quantitative method using artificial antibody to detect creatine kinases was developed. Linear epitope sequences were selected based on an artificial-epitope mapping strategy. Nine different MIPs corresponding to the selected peptides were then fabricated on QCM chips. The subtle conformational changes were also recognized by these chips.

Gay and Lesbian Youth Research: An East Asian Perspective

ERIC Educational Resources Information Center

Sugiyama, Takashi

2006-01-01

As globalization proceeded, the rights of sexual minority groups have become one of the human rights that cannot be ignored. However, recognizing sexuality as a human right and promoting educational practices which affect human rights policies, have been implemented mainly in the United States, Australia, New Zealand, and Europe. For example, the…

The Role of International Human Rights Norms in the Liberalization of Abortion Laws Globally

PubMed Central

Fine, Johanna B.; Mayall, Katherine; Sepúlveda, Lilian

2017-01-01

Abstract International and regional human rights norms have evolved significantly to recognize that the denial of abortion care in a range of circumstances violates women’s and girls’ fundamental human rights. These increasingly progressive standards have played a critical role in transforming national-level abortion laws by both influencing domestic high court decisions on abortion and serving as a critical resource in advancing law and policy reform. Courts in countries such as Argentina, Bolivia, Brazil, Colombia, and Nepal have directly incorporated these standards into groundbreaking cases liberalizing abortion laws and increasing women’s access to safe abortion services, demonstrating the influence of these human rights standards in advancing women’s reproductive freedom. These norms have also underpinned national-level abortion law and policy reform, including in countries such as Spain, Rwanda, Uruguay, and Peru. As these human rights norms further evolve and increasingly recognize abortion as a human rights imperative, these standards have the potential to bolster transformative jurisprudence and law and policy reform advancing women’s and girls’ full reproductive autonomy. PMID:28630542

Antigen-specific T cell therapies for cancer

PubMed Central

Manzo, Teresa; Heslop, Helen E.; Rooney, Cliona M.

2015-01-01

Adoptively transferred antigen-specific T cells that recognize tumor antigens through their native receptors have many potential benefits as treatment for virus-associated diseases and malignancies, due to their ability to selectively recognize tumor antigens, expand and persist to provide long-term protection. Infusions of T cells targeting Epstein–Barr virus (EBV) antigens have shown encouraging response rates in patients with post-transplant lymphoproliferative disease as well as EBV-positive lymphomas and nasopharyngeal cancer, although a recent study also showed that human papilloma virus-reactive T cells can induce complete regression of metastatic cervical cancer. This strategy is also being evaluated to target non-viral tumor-associated antigens. Targeting these less immunogenic antigens is more challenging, as tumor antigens are generally weak, and high avidity T cells specific for self-antigens are deleted in the thymus, but tumor responses have been reported. Current research focusses on defining factors that promote in vivo persistence of transferred cells and ameliorate the immunosuppressive microenvironment. To this end, investigators are evaluating the effects of combining adoptive transfer of antigen-specific T cells with other immunotherapy moieties such as checkpoint inhibitors. Genetic modification of infused T cells may also be used to overcome tumor evasion mechanisms, and vaccines may be used to promote in vivo proliferation. PMID:26160910

Uniformed Services University of the Health Sciences Journal. 2004/5 Edition

DTIC Science & Technology

2005-10-30

Goal 5: STEWARDSHIP: We will protect and enhance the human and physical resources of the University, optimize productivity , promote a...Other OSD- Recognized, Significant Areas of Support and Products Are Provided by USU for the MHS ...... 46-47 - Clinical Support for the Military...Comprehensive Annual Faculty Listing Report ......................................... 51-52 Two Significant OSD Awards Recognize the Multiple Products of USU

JPRS Report, Science & Technology, China

DTIC Science & Technology

1991-01-04

B27 Recognizes an Allospecific Determinant of HLA - B27 Lymphoblastoid Cell Lines [Shi Bingiun, et al.; ZHONGHUA WEISHENGWUXUE HE MIANYIXUE ZAZHI, No 5...Antibody Produced by industrialization of bioengineering. Immunization With the Synthetic Peptide From HLA - B27 Recognizes an Allospecific Determinant...Direct Detection of Human Immunodeficiency of HLA - B27 Lymphoblastoid Cell Lines Virus (HIV) Gene by the Polymerase Chain 40091003C Beijing ZHONGHUA

Nanoparticle Vaccines Adopting Virus-like Features for Enhanced Immune Potentiation

PubMed Central

Chattopadhyay, Saborni; Chen, Jui-Yi; Chen, Hui-Wen; Hu, Che-Ming Jack

2017-01-01

Synthetic nanoparticles play an increasingly significant role in vaccine design and development as many nanoparticle vaccines show improved safety and efficacy over conventional formulations. These nanoformulations are structurally similar to viruses, which are nanoscale pathogenic organisms that have served as a key selective pressure driving the evolution of our immune system. As a result, mechanisms behind the benefits of nanoparticle vaccines can often find analogue to the interaction dynamics between the immune system and viruses. This review covers the advances in vaccine nanotechnology with a perspective on the advantages of virus mimicry towards immune potentiation. It provides an overview to the different types of nanomaterials utilized for nanoparticle vaccine development, including functionalization strategies that bestow nanoparticles with virus-like features. As understanding of human immunity and vaccine mechanisms continue to evolve, recognizing the fundamental semblance between synthetic nanoparticles and viruses may offer an explanation for the superiority of nanoparticle vaccines over conventional vaccines and may spur new design rationales for future vaccine research. These nanoformulations are poised to provide solutions towards pressing and emerging human diseases. PMID:29071191

"The role of oxytocin in psychiatric disorders: A review of biological and therapeutic research findings"

PubMed Central

Cochran, David; Fallon, Daniel; Hill, Michael; Frazier, Jean A.

2014-01-01

Oxytocin is a peptide hormone integral in parturition, milk let-down, and maternal behaviors that has been demonstrated in animal studies to be important in the formation of pair bonds and in social behaviors. This hormone is increasingly recognized as an important regulator of human social behaviors, including social decision making, evaluating and responding to social stimuli, mediating social interactions, and forming social memories. In addition, oxytocin is intricately involved in a broad array of neuropsychiatric functions, and may be a common factor important in multiple psychiatric disorders such as autism, schizophrenia, mood and anxiety disorders. This review article examines the extant literature on the evidence for oxytocin dysfunction in a variety of psychiatric disorders and highlights the need for further research to understand the complex role of the oxytocin system in psychiatric disease to pave the way for developing new therapeutic modalities. Articles were selected that involved human participants with various psychiatric disorders, either comparing oxytocin biology to healthy controls or examining the effects of exogenous oxytocin administration. PMID:24651556

Evaluation of selected antiprotozoal drugs in the Babesia microti-hamster model.

PubMed Central

Marley, S E; Eberhard, M L; Steurer, F J; Ellis, W L; McGreevy, P B; Ruebush, T K

1997-01-01

The presently used therapy for Babesia microti infections, a combination of quinine and clindamycin, does not always result in parasitologic cures. To identify possible alternative chemotherapeutic agents for such infections, we screened, in the hamster-B. microti system, 12 antiprotozoal drugs that have either recently been released for human use or were in experimental stages of development at the Walter Reed Army Institute of Research for the treatment of malaria and leishmaniasis. Several well-recognized antimalarial drugs, such as mefloquine, halofantrine, artesunate, and artelenic acid, exhibited little or no effect on parasitemia. Two 8-aminoquinolines, WR006026 [8-(6-diethylaminohexylamino)-6-methoxy-4-methylquinoline dihydrochloride] and WR238605 [8-[(4-amino-1-methylbutyl)amino]-2,6-dimethoxy-4-methyl-5 -(3-trifluoromethylphenoxy-7) quinoline succinate], produced clearance of patent parasitemia. Furthermore, blood from infected hamsters treated with WR238605 via an intramuscular injection failed to infect naive hamsters on subpassage, thus producing a parasitologic cure. These two compounds merit further screening in other systems and may prove useful in treating human babesiosis. PMID:8980761

Strength Is in Numbers: Can Concordant Artificial Listeners Improve Prediction of Emotion from Speech?

PubMed

Martinelli, Eugenio; Mencattini, Arianna; Daprati, Elena; Di Natale, Corrado

2016-01-01

Humans can communicate their emotions by modulating facial expressions or the tone of their voice. Albeit numerous applications exist that enable machines to read facial emotions and recognize the content of verbal messages, methods for speech emotion recognition are still in their infancy. Yet, fast and reliable applications for emotion recognition are the obvious advancement of present 'intelligent personal assistants', and may have countless applications in diagnostics, rehabilitation and research. Taking inspiration from the dynamics of human group decision-making, we devised a novel speech emotion recognition system that applies, for the first time, a semi-supervised prediction model based on consensus. Three tests were carried out to compare this algorithm with traditional approaches. Labeling performances relative to a public database of spontaneous speeches are reported. The novel system appears to be fast, robust and less computationally demanding than traditional methods, allowing for easier implementation in portable voice-analyzers (as used in rehabilitation, research, industry, etc.) and for applications in the research domain (such as real-time pairing of stimuli to participants' emotional state, selective/differential data collection based on emotional content, etc.).

Germline-encoded neutralization of a Staphylococcus aureus virulence factor by the human antibody repertoire.

PubMed

Yeung, Yik Andy; Foletti, Davide; Deng, Xiaodi; Abdiche, Yasmina; Strop, Pavel; Glanville, Jacob; Pitts, Steven; Lindquist, Kevin; Sundar, Purnima D; Sirota, Marina; Hasa-Moreno, Adela; Pham, Amber; Melton Witt, Jody; Ni, Irene; Pons, Jaume; Shelton, David; Rajpal, Arvind; Chaparro-Riggers, Javier

2016-11-18

Staphylococcus aureus is both an important pathogen and a human commensal. To explore this ambivalent relationship between host and microbe, we analysed the memory humoral response against IsdB, a protein involved in iron acquisition, in four healthy donors. Here we show that in all donors a heavily biased use of two immunoglobulin heavy chain germlines generated high affinity (pM) antibodies that neutralize the two IsdB NEAT domains, IGHV4-39 for NEAT1 and IGHV1-69 for NEAT2. In contrast to the typical antibody/antigen interactions, the binding is primarily driven by the germline-encoded hydrophobic CDRH-2 motifs of IGHV1-69 and IGHV4-39, with a binding mechanism nearly identical for each antibody derived from different donors. Our results suggest that IGHV1-69 and IGHV4-39, while part of the adaptive immune system, may have evolved under selection pressure to encode a binding motif innately capable of recognizing and neutralizing a structurally conserved protein domain involved in pathogen iron acquisition.

Habitat selection by marine larvae in changing chemical environments.

PubMed

Lecchini, D; Dixson, D L; Lecellier, G; Roux, N; Frédérich, B; Besson, M; Tanaka, Y; Banaigs, B; Nakamura, Y

2017-01-15

The replenishment and persistence of marine species is contingent on dispersing larvae locating suitable habitat and surviving to a reproductive stage. Pelagic larvae rely on environmental cues to make behavioural decisions with chemical information being important for habitat selection at settlement. We explored the sensory world of crustaceans and fishes focusing on the impact anthropogenic alterations (ocean acidification, red soil, pesticide) have on conspecific chemical signals used by larvae for habitat selection. Crustacean (Stenopus hispidus) and fish (Chromis viridis) larvae recognized their conspecifics via chemical signals under control conditions. In the presence of acidified water, red soil or pesticide, the ability of larvae to chemically recognize conspecific cues was altered. Our study highlights that recruitment potential on coral reefs may decrease due to anthropogenic stressors. If so, populations of fishes and crustaceans will continue their rapid decline; larval recruitment will not replace and sustain the adult populations on degraded reefs. Copyright © 2016 Elsevier Ltd. All rights reserved.

Continuous Human Action Recognition Using Depth-MHI-HOG and a Spotter Model

PubMed Central

Eum, Hyukmin; Yoon, Changyong; Lee, Heejin; Park, Mignon

2015-01-01

In this paper, we propose a new method for spotting and recognizing continuous human actions using a vision sensor. The method is comprised of depth-MHI-HOG (DMH), action modeling, action spotting, and recognition. First, to effectively separate the foreground from background, we propose a method called DMH. It includes a standard structure for segmenting images and extracting features by using depth information, MHI, and HOG. Second, action modeling is performed to model various actions using extracted features. The modeling of actions is performed by creating sequences of actions through k-means clustering; these sequences constitute HMM input. Third, a method of action spotting is proposed to filter meaningless actions from continuous actions and to identify precise start and end points of actions. By employing the spotter model, the proposed method improves action recognition performance. Finally, the proposed method recognizes actions based on start and end points. We evaluate recognition performance by employing the proposed method to obtain and compare probabilities by applying input sequences in action models and the spotter model. Through various experiments, we demonstrate that the proposed method is efficient for recognizing continuous human actions in real environments. PMID:25742172

Abeta targets of the biosimilar antibodies of Bapineuzumab, Crenezumab, Solanezumab in comparison to an antibody against N‑truncated Abeta in sporadic Alzheimer disease cases and mouse models.

PubMed

Bouter, Yvonne; Lopez Noguerola, Jose Socrates; Tucholla, Petra; Crespi, Gabriela A N; Parker, Michael W; Wiltfang, Jens; Miles, Luke A; Bayer, Thomas A

2015-11-01

Solanezumab and Crenezumab are two humanized antibodies targeting Amyloid-β (Aβ) which are currently tested in multiple clinical trials for the prevention of Alzheimer's disease. However, there is a scientific discussion ongoing about the target engagement of these antibodies. Here, we report the immunohistochemical staining profiles of biosimilar antibodies of Solanezumab, Crenezumab and Bapineuzumab in human formalin-fixed, paraffin-embedded tissue and human fresh frozen tissue. Furthermore, we performed a direct comparative immunohistochemistry analysis of the biosimilar versions of the humanized antibodies in different mouse models including 5XFAD, Tg4-42, TBA42, APP/PS1KI, 3xTg. The staining pattern with these humanized antibodies revealed a surprisingly similar profile. All three antibodies detected plaques, cerebral amyloid angiopathy and intraneuronal Aβ in a similar fashion. Remarkably, Solanezumab showed a strong binding affinity to plaques. We also reaffirmed that Bapineuzumab does not recognize N-truncated or modified Aβ, while Solanezumab and Crenezumab do detect N-terminally modified Aβ peptides Aβ4-42 and pyroglutamate Aβ3-42. In addition, we compared the results with the staining pattern of the mouse NT4X antibody that recognizes specifically Aβ4-42 and pyroglutamate Aβ3-42, but not full-length Aβ1-42. In contrast to the biosimilar antibodies of Solanezumab, Crenezumab and Bapineuzumab, the murine NT4X antibody shows a unique target engagement. NT4X does barely cross-react with amyloid plaques in human tissue. It does, however, detect cerebral amyloid angiopathy in human tissue. In Alzheimer mouse models, NT4X detects intraneuronal Aβ and plaques comparable to the humanized antibodies. In conclusion, the biosimilar antibodies Solanezumab, Crenezumab and Bapineuzumab strongly react with amyloid plaques, which are in contrast to the NT4X antibody that hardly recognizes plaques in human tissue. Therefore, NT4X is the first of a new class of therapeutic antibodies.

Targeting gene expression selectively in cancer cells by using the progression-elevated gene-3 promoter.

PubMed

Su, Zhao-Zhong; Sarkar, Devanand; Emdad, Luni; Duigou, Gregory J; Young, Charles S H; Ware, Joy; Randolph, Aaron; Valerie, Kristoffer; Fisher, Paul B

2005-01-25

One impediment to effective cancer-specific gene therapy is the rarity of regulatory sequences targeting gene expression selectively in tumor cells. Although many tissue-specific promoters are recognized, few cancer-selective gene promoters are available. Progression-elevated gene-3 (PEG-3) is a rodent gene identified by subtraction hybridization that displays elevated expression as a function of transformation by diversely acting oncogenes, DNA damage, and cancer cell progression. The promoter of PEG-3, PEG-Prom, displays robust expression in a broad spectrum of human cancer cell lines with marginal expression in normal cellular counterparts. Whereas GFP expression, when under the control of a CMV promoter, is detected in both normal and cancer cells, when GFP is expressed under the control of the PEG-Prom, cancer-selective expression is evident. Mutational analysis identifies the AP-1 and PEA-3 transcription factors as primary mediators of selective, cancer-specific expression of the PEG-Prom. Synthesis of apoptosis-inducing genes, under the control of the CMV promoter, inhibits the growth of both normal and cancer cells, whereas PEG-Prom-mediated expression of these genes kills only cancer cells and spares normal cells. The efficacy of the PEG-Prom as part of a cancer gene therapeutic regimen is further documented by in vivo experiments in which PEG-Prom-controlled expression of an apoptosis-inducing gene completely inhibited prostate cancer xenograft growth in nude mice. These compelling observations indicate that the PEG-Prom, with its cancer-specific expression, provides a means of selectively delivering genes to cancer cells, thereby providing a crucial component in developing effective cancer gene therapies.

Presentations of Shape in Object Recognition and Long-Term Visual Memory

DTIC Science & Technology

1994-04-05

theory of human image understanding . Psychological Review, 94, 115-147. Biederman, I., & Gerhardstein, P. C. (1993). Recognizing depth-rotated...Kybemetik. Submitted to Journal of Experimental Psychology: Human Perception and Performance. REFERENCES Biederman, I. (1987). Recognition-by-components: A

Tracking the pathway of arsenic metabolism

EPA Science Inventory

Although the toxic and carcinogenic properties of arsenic have been recognized for centuries, only in the past few decades has research focused on understanding the metabolic fate of arsenic in humans and relating metabolism to adverse health effects. In humans, conversion of in...

Chromosomal duplications in bacteria, fruit flies, and humans

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

Lupski, J.R.; Weinstock, G.M.; Roth, J.R.

1996-01-01

Tandem duplication of chromosomal segments has been recognized as a frequent mutational mechanism in several genetic model systems. In bacteria, fruit flies, and humans, duplications form by similar molecular mechanisms and appear to be important in genome evolution. 80 refs.

Marker-assisted selection for recognizing wheat mutant genotypes carrying HMW glutenin alleles related to baking quality.

PubMed

Zamani, Mohammad Javad; Bihamta, Mohammad Reza; Naserian Khiabani, Behnam; Tahernezhad, Zahra; Hallajian, Mohammad Taher; Shamsi, Marzieh Varasteh

2014-01-01

Allelic diversity of HMW glutenin loci in several studies revealed that allelic combinations affect dough quality. Dx5 + Dy10 subunits are related to good baking quality and Dx2 + Dy12 are related to undesirable baking quality. One of the most regular methods to evaluate the baking quality is SDS-PAGE which is used to improve baking quality labs. Marker-assisted selection is the method which can recognize the alleles related to baking quality and this method is based on polymerase chain reaction. 10 pairs of specific primers related to Dx2, Dx2.1, Dx5, Dy10, and Dy12 subunits were used for recognizing baking quality of some wheat varieties and some mutant genotypes. Only 5 pairs of them could show the specific bands. All subunits were recognized by the primers except Dx2.1. Some of the primers were extracted from previous studies and the others were designed based on D genome subunits of wheat. SDS-PAGE method accomplished having confidence in these marker's results. To realize the effect of mutation, seed storage proteins were measured. It showed that mutation had effect on the amount of seed storage protein on the mutant seeds (which showed polymorphism).

Are Africans, Europeans, and Asians different "races"? A guided-inquiry lab for introducing undergraduate students to genetic diversity and preparing them to study natural selection.

PubMed

Kalinowski, Steven T; Andrews, Tessa M; Leonard, Mary J; Snodgrass, Meagan

2012-01-01

Many students do not recognize that individual organisms within populations vary, and this may make it difficult for them to recognize the essential role variation plays in natural selection. Also, many students have weak scientific reasoning skills, and this makes it difficult for them to recognize misconceptions they might have. This paper describes a 2-h laboratory for college students that introduces them to genetic diversity and gives them practice using hypothetico-deductive reasoning. In brief, the lab presents students with DNA sequences from Africans, Europeans, and Asians, and asks students to determine whether people from each continent qualify as distinct "races." Comparison of the DNA sequences shows that people on each continent are not more similar to one another than to people on other continents, and therefore do not qualify as distinct races. Ninety-four percent of our students reported that the laboratory was interesting, and 79% reported that it was a valuable learning experience. We developed and used a survey to measure the extent to which students recognized variation and its significance within populations and showed that the lab increased student awareness of variation. We also showed that the lab improved the ability of students to construct hypothetico-deductive arguments.

Activity of the hypoxia-activated pro-drug TH-302 in hypoxic and perivascular regions of solid tumors and its potential to enhance therapeutic effects of chemotherapy.

PubMed

Saggar, Jasdeep K; Tannock, Ian F

2014-06-01

Many chemotherapy drugs have poor therapeutic activity in regions distant from tumor blood vessels because of poor tissue penetration and low cytotoxic activity against slowly-proliferating cells. The hypoxia-activated pro-drug TH-302 may have selective toxicity for hypoxic and neighboring cells in tumors. Here we characterize the spatial distribution and ability of TH-302 to selectively target hypoxic regions and complement the effect of doxorubicin and docetaxel by modifying biomarker distribution. Athymic nude mice bearing human breast MCF-7 or prostate PC-3 tumors were treated with doxorubicin or docetaxel respectively and TH-302 alone or in combination. Biomarkers of drug effect including γH2aX (a marker of DNA damage), cleaved caspase-3 or -6 (markers of apoptosis) and reduction in Ki-67 (a marker of cell proliferation) were quantified in tumor sections in relation to functional blood vessels (recognized by DiOC7) and hypoxia (recognized by EF5) using immunohistochemistry. γH2aX expression at 10 min and cleaved caspase-3 or -6 at 24 hr after doxorubicin or docetaxel decreased with increasing distance from tumor blood vessels, with minimal expression in hypoxic regions; maximum reduction in Ki67 levels was observed in regions closest to vasculature at 24 hr. TH-302 induced maximal cell damage in hypoxic and neighboring regions, but was also active in tumor regions closer to blood vessels. TH-302 given 4 hr before doxorubicin or docetaxel increased DNA damage and apoptosis throughout the tumor compared to chemotherapy alone. When given with doxorubicin or docetaxel, TH-302 complements and enhances anticancer effects in both perivascular and hypoxic regions but also increases toxicity. © 2013 UICC.

Adaptive Learning Resources Sequencing in Educational Hypermedia Systems

ERIC Educational Resources Information Center

Karampiperis, Pythagoras; Sampson, Demetrios

2005-01-01

Adaptive learning resources selection and sequencing is recognized as among the most interesting research questions in adaptive educational hypermedia systems (AEHS). In order to adaptively select and sequence learning resources in AEHS, the definition of adaptation rules contained in the Adaptation Model, is required. Although, some efforts have…

Getting Good Advice. How and When to Use Consultants.

ERIC Educational Resources Information Center

Radock, Michael

1981-01-01

Suggestions on when to seek a consultant and how to select the one best suited to collegiate needs are discussed. Reliance on recognized firms, professional organizations, and selective free-lance consultants is recommended. Being well-prepared, planning the consultant's time schedule carefully, clarifying arrangements, and setting the terms are…

Perceptions Regarding Selected Educational Strategies Used by Extension Educators

ERIC Educational Resources Information Center

Kwaw-Mensah, David; Martin, Robert A.

2013-01-01

Purpose: The purpose of this study was to identify the perceptions that extension educators in the North Central region of the United States hold regarding selected educational strategies pertaining to livestock waste management education. Livestock waste management education has been recognized as one of extension's major initiatives in the…

Trichinella spiralis newborn larvae: characterization of a stage specific serine proteinase expression, NBL1, using monoclonal antibodies.

PubMed

Yang, Yong; Lacour, Sandrine A; Lainé-Prade, Véronique; Versillé, Nicolas; Grasset-Chevillot, Aurélie; Feng, Shuang; Liu, Ming Yuan; Boireau, Pascal; Vallée, Isabelle

2015-05-01

Trichinella spiralis is an intracellular parasitic nematode of mammalian skeletal muscle, causing a serious zoonotic disease in humans and showing a high economic impact mainly in pig breeding. Serine proteinases of T. spiralis play important roles in the host-parasite interactions mediating host invasion. In this study, we have focused on newborn larvae (NBL-1), the first identified serine proteinase from the NBL stage of T. spiralis. Five monoclonal antibodies (mAbs) directed against the C-terminal part of NBL1, were produced. These mAbs were IgG1κ isotype and specifically recognized as a common motif of 10 amino acids (PSSGSRPTYP). Selected mAbs were further characterized using antigens from various developmental stages of T. spiralis. Western blot revealed that selected mAbs reacted with the native NBL1 at Mr 50 kDa in the adult and NBL mixed antigens and NBL stage alone. Indirect immunofluorescence analysis revealed that selected mAbs intensely stained only the embryos within the gravid females and the NBL. Thus, the produced mAbs are useful tools for the characterization of NBL1 as a major antigen of Trichinella involved in the invasion of the host but also for the development of new serological tests with an early detection of T. spiralis infection.

The law of cooperation: Comment on "Universal scaling for the dilemma strength in evolutionary games" by Z. Wang et al.

NASA Astrophysics Data System (ADS)

Ichinose, Genki

2015-09-01

Cooperation is a behavior that benefits others while incurring costs to the actor. Thus, natural selection favors defection (non-cooperation), which unilaterally takes the benefits without paying any costs, rather than cooperation. Despite this logical consequence, reality is the opposite: Cooperation is ubiquitous at any level from genomes to human societies. This contradiction is known as the puzzle of the evolution of cooperation. For a long time, evolutionary game theorists have used the prisoner's dilemma game (PD) and the chicken game (CH) as the standard models to solve this puzzle. For these researchers, it is recognized that a specific mechanism is needed for the evolution of cooperation [1]. Five mechanisms are proposed: kin selection, direct reciprocity, indirect reciprocity, network reciprocity, and group selection. By using the donor and recipient game (D&R), which is one of the particular forms of PD, Nowak theoretically showed that once benefit (b), cost (c), and the other one or two parameters for each mechanism are given, we (evolutionary game theorists) can immediately know whether cooperation evolves [1]. The point here is that he included those unique parameters for each mechanism into PD and then reformulated the payoff matrix. Therefore, we can use this extended PD as the first scaling parameters.

Phosphoglycerate kinase and fructose bisphosphate aldolase of Candida albicans as new antigens recognized by human salivary IgA.

PubMed

Calcedo, Roberto; Ramirez-Garcia, Andoni; Abad, Ana; Rementeria, Aitor; Pontón, José; Hernando, Fernando Luis

2012-01-01

Candida albicans is an opportunistic dimorphic fungus commonly present in the human oral cavity that causes infections in immunocompromised patients. The antigen variability, influenced by growth conditions, is a pathogenicity factor. To determine the effect of nutritional and heat stress on the antigen expression of C. albicans, and to identify major antigens recognized by human salivary secretory immunoglobulin A (sIgA). Under various different nutritional conditions, heat shock was induced in C. albicans cells in stationary and exponential growth phases. The expression of protein determinants of C. albicans was assessed by Western blot analysis against human saliva. The antigens were purified and characterized by two-dimensional electrophoresis and identified by protein microsequencing. Five antigens recognized by salivary IgA were characterized as mannoproteins due to their reactivity with concanavalin A. They did not show reactivity with anti-heat shock protein monoclonal antibodies. Two of them (42 and 36 kDa) were found to be regulated by heat shock and by nutritional stress and they were identified as phosphoglycerate kinase and fructose bisphosphate aldolase, respectively. These glycolytic enzymes are major antigens of C. albicans, and their differential expression and recognition by the mucosal immune response system could be involved in protection against oral infection. Copyright © 2011 Revista Iberoamericana de Micología. Published by Elsevier Espana. All rights reserved.

Facial Expressions and Ability to Recognize Emotions From Eyes or Mouth in Children

PubMed Central

Guarnera, Maria; Hichy, Zira; Cascio, Maura I.; Carrubba, Stefano

2015-01-01

This research aims to contribute to the literature on the ability to recognize anger, happiness, fear, surprise, sadness, disgust and neutral emotions from facial information. By investigating children’s performance in detecting these emotions from a specific face region, we were interested to know whether children would show differences in recognizing these expressions from the upper or lower face, and if any difference between specific facial regions depended on the emotion in question. For this purpose, a group of 6-7 year-old children was selected. Participants were asked to recognize emotions by using a labeling task with three stimulus types (region of the eyes, of the mouth, and full face). The findings seem to indicate that children correctly recognize basic facial expressions when pictures represent the whole face, except for a neutral expression, which was recognized from the mouth, and sadness, which was recognized from the eyes. Children are also able to identify anger from the eyes as well as from the whole face. With respect to gender differences, there is no female advantage in emotional recognition. The results indicate a significant interaction ‘gender x face region’ only for anger and neutral emotions. PMID:27247651

Oligonucleotide aptamers against tyrosine kinase receptors: Prospect for anticancer applications.

PubMed

Camorani, Simona; Crescenzi, Elvira; Fedele, Monica; Cerchia, Laura

2018-04-01

Transmembrane receptor tyrosine kinases (RTKs) play crucial roles in cancer cell proliferation, survival, migration and differentiation. Area of intense research is searching for effective anticancer therapies targeting these receptors and, to date, several monoclonal antibodies and small-molecule tyrosine kinase inhibitors have entered the clinic. However, some of these drugs show limited efficacy and give rise to acquired resistance. Emerging highly selective compounds for anticancer therapy are oligonucleotide aptamers that interact with their targets by recognizing a specific three-dimensional structure. Because of their nucleic acid nature, the rational design of advanced strategies to manipulate aptamers for both diagnostic and therapeutic applications is greatly simplified over antibodies. In this manuscript, we will provide a comprehensive overview of oligonucleotide aptamers as next generation strategies to efficiently target RTKs in human cancers. Copyright © 2018 Elsevier B.V. All rights reserved.

AP1 Keeps Chromatin Poised for Action | Center for Cancer Research

Cancer.gov

The human genome harbors gene-encoding DNA, the blueprint for building proteins that regulate cellular function. Embedded across the genome, in non-coding regions, are DNA elements to which regulatory factors bind. The interaction of regulatory factors with DNA at these sites modifies gene expression to modulate cell activity. In cells, DNA exists in a complex with proteins called chromatin that compacts the DNA in the nucleus, strongly restricting access to DNA sequences. As a result, regulatory factors only interact with a small subset of their potential binding elements in a given cell to regulate genes. How factors recognize and select sites in chromatin across the genome is not well understood -- but several discoveries in CCR’s Laboratory of Receptor Biology and Gene Expression (LRBGE) have shed light on the mechanisms that direct factors to DNA.

Antibodies against human cytochrome P-450db1 in autoimmune hepatitis type II.

PubMed

Zanger, U M; Hauri, H P; Loeper, J; Homberg, J C; Meyer, U A

1988-11-01

In a subgroup of children with chronic active hepatitis, circulating autoantibodies occur that bind to liver and kidney endoplasmic reticulum (anti-liver/kidney microsome antibody type I or anti-LKM1). Anti-LKM1 titers follow the severity of the disease and the presence of these antibodies serves as a diagnostic marker for this autoimmune hepatitis type II. We demonstrate that anti-LKM1 IgGs specifically inhibit the hydroxylation of bufuralol in human liver microsomes. Using two assay systems with different selectivity for the two cytochrome P-450 isozymes catalyzing bufuralol metabolism in human liver, we show that anti-LKM1 exclusively recognizes cytochrome P-450db1. Immunopurification of the LKM1 antigen from solubilized human liver microsomes resulted in an electrophoretically homogenous protein that had the same molecular mass (50 kDa) as purified P-450db1 and an identical N-terminal amino acid sequence. Recognition of both purified P-450db1 and the immunoisolated protein on western blots by several monoclonal antibodies confirmed the identity of the LKM1 antigen with cytochrome P-450db1. Cytochrome P-450db1 has been identified as the target of a common genetic polymorphism of drug oxidation. However, the relationship between the polymorphic cytochrome P-450db1 and the appearance of anti-LKM1 autoantibodies as well as their role in the pathogenesis of chronic active hepatitis remains speculative.

Smart unattended sensor networks with scene understanding capabilities

NASA Astrophysics Data System (ADS)

Kuvich, Gary

2006-05-01

Unattended sensor systems are new technologies that are supposed to provide enhanced situation awareness to military and law enforcement agencies. A network of such sensors cannot be very effective in field conditions only if it can transmit visual information to human operators or alert them on motion. In the real field conditions, events may happen in many nodes of a network simultaneously. But the real number of control personnel is always limited, and attention of human operators can be simply attracted to particular network nodes, while more dangerous threat may be unnoticed at the same time in the other nodes. Sensor networks would be more effective if equipped with a system that is similar to human vision in its abilities to understand visual information. Human vision uses for that a rough but wide peripheral system that tracks motions and regions of interests, narrow but precise foveal vision that analyzes and recognizes objects in the center of selected region of interest, and visual intelligence that provides scene and object contexts and resolves ambiguity and uncertainty in the visual information. Biologically-inspired Network-Symbolic models convert image information into an 'understandable' Network-Symbolic format, which is similar to relational knowledge models. The equivalent of interaction between peripheral and foveal systems in the network-symbolic system is achieved via interaction between Visual and Object Buffers and the top-level knowledge system.

T cell receptor αβ diversity inversely correlates with pathogen-specific antibody levels in human cytomegalovirus infection.

PubMed

Wang, George C; Dash, Pradyot; McCullers, Jonathan A; Doherty, Peter C; Thomas, Paul G

2012-04-04

A diverse T cell receptor (TCR) repertoire capable of recognizing a broad range of antigenic peptides is thought to be central to effective pathogen-specific immunity by counteracting escape mutations, selecting high-avidity T cells, and providing T cell specificities with comprehensive functional characteristics. However, evidence that TCR diversity is important for the successful control of human infections is limited. A single-cell strategy for the clonotypic analysis of human CD8⁺ TCRαβ repertoires was used to probe the diversity and magnitude of individual human cytomegalovirus (CMV)-specific CD8⁺ T cells recovered directly ex vivo. We found that CD8⁺ TCRαβ repertoire diversity, but not the size of the CD8⁺ T cell response, was inversely related to circulating CMV-specific antibody levels, a measure that has been correlated epidemiologically with differential mortality risks and found here to be higher in persons with detectable (versus undetectable) CMV viral loads. Overall, our findings indicate that CD8⁺ T cell diversity may be more important than T cell abundance in limiting the negative consequences of CMV persistence, demonstrate high prevalence of both TCRα and TCRβ public motif usage, and suggest that a highly diverse TCRαβ repertoire may be an important benchmark and target in the success of immunotherapeutic strategies.

Recognition of Propionibacterium acnes by human TLR2 heterodimers.

PubMed

Su, Qi; Grabowski, Maria; Weindl, Günther

2017-02-01

Propionibacterium acnes has been considered as a crucial contributor to the pathogenesis of acne vulgaris. The interaction between P. acnes and the host is mainly mediated by Toll like receptor (TLR) 2 recognition. TLR2 homodimers recognize P. acnes in mice, but here we describe the prerequisite of TLR2/1 and TLR2/6 heterodimers in human cells for P. acnes recognition. P. acnes-induced NF-κB and AP-1activation observed in HEK hTLR2-transfected but not control cells confirmed the specificity of TLR2 recognition. The activation was blocked by neutralizing antibodies against TLR2, TLR1 and TLR6, as well as the TLR2 antagonist CU-CPT22, which showed no selectivity towards human TLR2 heterodimers. The combination of anti-TLR1 and anti-TLR6 antibodies completely abrogated activation by P. acnes. In primary human keratinocytes, P. acnes-increased NF-κB phosphorylation was inhibited by anti-TLR6 and anti-TLR2 antibodies. Furthermore, P. acnes-induced inflammatory responses were impaired by anti-TLR2 neutralizing antibodies and fully blocked by CU-CPT22. Our study suggests species-specific recognition of P. acnes by TLR2 heterodimers which can be exploited therapeutically by small molecules targeting TLR2 for the control of inflammatory responses. Copyright © 2016 Elsevier GmbH. All rights reserved.

A repeatable assembling and disassembling electrochemical aptamer cytosensor for ultrasensitive and highly selective detection of human liver cancer cells.

PubMed

Sun, Duanping; Lu, Jing; Chen, Zuanguang; Yu, Yanyan; Mo, Manni

2015-07-23

In this work, a repeatable assembling and disassembling electrochemical aptamer cytosensor was proposed for the sensitive detection of human liver hepatocellular carcinoma cells (HepG2) based on a dual recognition and signal amplification strategy. A high-affinity thiolated TLS11a aptamer, covalently attached to a gold electrode through Au-thiol interactions, was adopted to recognize and capture the target HepG2 cells. Meanwhile, the G-quadruplex/hemin/aptamer and horseradish peroxidase (HRP) modified gold nanoparticles (G-quadruplex/hemin/aptamer-AuNPs-HRP) nanoprobe was designed. It could be used for electrochemical cytosensing with specific recognition and enzymatic signal amplification of HRP and G-quadruplex/hemin HRP-mimicking DNAzyme. With the nanoprobes as recognizing probes, the HepG2 cancer cells were captured to fabricate an aptamer-cell-nanoprobes sandwich-like superstructure on a gold electrode surface. The proposed electrochemical cytosensor delivered a wide detection range from 1×10(2) to 1×10(7) cells mL(-1) and high sensitivity with a low detection limit of 30 cells mL(-1). Furthermore, after the electrochemical detection, the activation potential of -0.9 to -1.7V was performed to break Au-thiol bond and regenerate a bare gold electrode surface, while maintaining the good characteristic of being used repeatedly. The changes of gold electrode behavior after assembling and desorption processes were investigated by electrochemical impedance spectroscopy and cyclic voltammetry techniques. These results indicate that the cytosensor has great potential in disease diagnostic of cancers and opens new insight into the reusable gold electrode with repeatable assembling and disassembling in the electrochemical sensing. Copyright © 2015 Elsevier B.V. All rights reserved.

Dendritic Cell-specific Intercellular Adhesion Molecule 3-grabbing Non-integrin (DC-SIGN) Recognizes a Novel Ligand, Mac-2-binding Protein, Characteristically Expressed on Human Colorectal Carcinomas*

PubMed Central

Nonaka, Motohiro; Ma, Bruce Yong; Imaeda, Hirotsugu; Kawabe, Keiko; Kawasaki, Nobuko; Hodohara, Keiko; Kawasaki, Nana; Andoh, Akira; Fujiyama, Yoshihide; Kawasaki, Toshisuke

2011-01-01

Dendritic cell (DC)-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN) is a type II transmembrane C-type lectin expressed on DCs such as myeloid DCs and monocyte-derived DCs (MoDCs). Recently, we have reported that DC-SIGN interacts with carcinoembryonic antigen (CEA) expressed on colorectal carcinoma cells. CEA is one of the most widely used tumor markers for gastrointestinal cancers such as colorectal cancer. On the other hand, other groups have reported that the level of Mac-2-binding protein (Mac-2BP) increases in patients with pancreatic, breast, and lung cancers, virus infections such as human immunodeficiency virus and hepatitis C virus, and autoimmune diseases. Here, we first identified Mac-2BP expressed on several colorectal carcinoma cell lines as a novel DC-SIGN ligand through affinity chromatography and mass spectrometry. Interestingly, we found that DC-SIGN selectively recognizes Mac-2BP derived from some colorectal carcinomas but not from the other ones. Furthermore, we found that the α1-3,4-fucose moieties of Le glycans expressed on DC-SIGN-binding Mac-2BP were important for recognition. DC-SIGN-dependent cellular interactions between immature MoDCs and colorectal carcinoma cells significantly inhibited MoDC functional maturation, suggesting that Mac-2BP may provide a tolerogenic microenvironment for colorectal carcinoma cells through DC-SIGN-dependent recognition. Importantly, Mac-2BP was detected as a predominant DC-SIGN ligand expressed on some primary colorectal cancer tissues from certain parts of patients in comparison with CEA from other parts, suggesting that DC-SIGN-binding Mac-2BP bearing tumor-associated Le glycans may become a novel potential colorectal cancer biomarker for some patients instead of CEA. PMID:21515679

Diverse specificity and effector function among human antibodies to HIV-1 envelope glycoprotein epitopes exposed by CD4 binding

DOE PAGES

Guan, Yongjun; Pazgier, Marzena; Sajadi, Mohammad M.; ...

2012-12-13

The HIV-1 envelope glycoprotein (Env) undergoes conformational transitions consequent to CD4 binding and coreceptor engagement during viral entry. The physical steps in this process are becoming defined, but less is known about their significance as targets of antibodies potentially protective against HIV-1 infection. Here we probe the functional significance of transitional epitope exposure by characterizing 41 human mAbs specific for epitopes exposed on trimeric Env after CD4 engagement. These mAbs recognize three epitope clusters: cluster A, the gp120 face occluded by gp41 in trimeric Env; cluster B, a region proximal to the coreceptor-binding site (CoRBS) and involving the V1/V2 domain;more » and cluster C, the coreceptor-binding site. The mAbs were evaluated functionally by antibody-dependent, cell-mediated cytotoxicity (ADCC) and for neutralization of Tiers 1 and 2 pseudoviruses. All three clusters included mAbs mediating ADCC. However, there was a strong potency bias for cluster A, which harbors at least three potent ADCC epitopes whose cognate mAbs have electropositive paratopes. Cluster A epitopes are functional ADCC targets during viral entry in an assay format using virion-sensitized target cells. In contrast, only cluster C contained epitopes that were recognized by neutralizing mAbs. There was significant diversity in breadth and potency that correlated with epitope fine specificity. In contrast, ADCC potency had no relationship with neutralization potency or breadth for any epitope cluster. In conclusion, Fc-mediated effector function and neutralization coselect with specificity in anti-Env antibody responses, but the nature of selection is distinct for these two antiviral activities.« less

Speech Acquisition and Automatic Speech Recognition for Integrated Spacesuit Audio Systems

NASA Technical Reports Server (NTRS)

Huang, Yiteng; Chen, Jingdong; Chen, Shaoyan

2010-01-01

A voice-command human-machine interface system has been developed for spacesuit extravehicular activity (EVA) missions. A multichannel acoustic signal processing method has been created for distant speech acquisition in noisy and reverberant environments. This technology reduces noise by exploiting differences in the statistical nature of signal (i.e., speech) and noise that exists in the spatial and temporal domains. As a result, the automatic speech recognition (ASR) accuracy can be improved to the level at which crewmembers would find the speech interface useful. The developed speech human/machine interface will enable both crewmember usability and operational efficiency. It can enjoy a fast rate of data/text entry, small overall size, and can be lightweight. In addition, this design will free the hands and eyes of a suited crewmember. The system components and steps include beam forming/multi-channel noise reduction, single-channel noise reduction, speech feature extraction, feature transformation and normalization, feature compression, model adaption, ASR HMM (Hidden Markov Model) training, and ASR decoding. A state-of-the-art phoneme recognizer can obtain an accuracy rate of 65 percent when the training and testing data are free of noise. When it is used in spacesuits, the rate drops to about 33 percent. With the developed microphone array speech-processing technologies, the performance is improved and the phoneme recognition accuracy rate rises to 44 percent. The recognizer can be further improved by combining the microphone array and HMM model adaptation techniques and using speech samples collected from inside spacesuits. In addition, arithmetic complexity models for the major HMMbased ASR components were developed. They can help real-time ASR system designers select proper tasks when in the face of constraints in computational resources.

Identification of the Single Immunodominant Region of the Native Human CC Chemokine Receptor 6 Recognized by Mouse Monoclonal Antibodies.

PubMed

Dorgham, Karim; Dejou, Cécile; Piesse, Christophe; Gorochov, Guy; Pène, Jérôme; Yssel, Hans

2016-01-01

Chemokines and their receptors play an important role in cell trafficking and recruitment. The CCR6 chemokine receptor, selectively expressed on leukocyte populations, has been shown to play a deleterious role in the pathogenesis of various chronic inflammatory diseases and, as such, may constitute a prime target in the development of immunotherapeutic treatment. However, to date no neutralizing mouse monoclonal antibodies (mAbs) specific for this chemokine receptor have been reported, whereas information on small molecules capable of interfering with the interaction of CCR6 and its ligands is scant. Here, we report the failure to generate neutralizing mouse mAbs specific for human (hu)CCR6. Immunization of mice with peptides mimicking extracellular domains, potentially involved in CCR6 function, failed to induce Abs reactive with the native receptor. Although the use of NIH-3T3 cells expressing huCCR6 resulted in the isolation of mAbs specific for this receptor, they were not able to block the interaction between huCCR6 and huCCL20. Investigation of the anti-huCCR6 mAbs generated in the present study, as well as those commercially available, show that all mAbs invariably recognize a unique, non-neutralizing, immunodominant region in the first part of its N-terminal domain. Together, these results indicate that the generation of potential neutralizing anti-huCCR6 mAbs in the mouse is unlikely to succeed and that alternative techniques, such as the use of other animal species for immunization, might constitute a better approach to generate such a potentially therapeutic tool for the treatment of inflammatory disease.

Use of short-term test systems for the prediction of the hazard represented by potential chemical carcinogens

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

Glass, L.R.; Jones, T.D.; Easterly, C.E.

1990-10-01

It has been hypothesized that results from short-term bioassays will ultimately provide information that will be useful for human health hazard assessment. Historically, the validity of the short-term tests has been assessed using the framework of the epidemiologic/medical screens. In this context, the results of the carcinogen (long-term) bioassay is generally used as the standard. However, this approach is widely recognized as being biased and, because it employs qualitative data, cannot be used to assist in isolating those compounds which may represent a more significant toxicologic hazard than others. In contrast, the goal of this research is to address themore » problem of evaluating the utility of the short-term tests for hazard assessment using an alternative method of investigation. Chemicals were selected mostly from the list of carcinogens published by the International Agency for Research on Carcinogens (IARC); a few other chemicals commonly recognized as hazardous were included. Tumorigenicity and mutagenicity data on 52 chemicals were obtained from the Registry of Toxic Effects of Chemical Substances (RTECS) and were analyzed using a relative potency approach. The data were evaluated in a format which allowed for a comparison of the ranking of the mutagenic relative potencies of the compounds (as estimated using short-term data) vs. the ranking of the tumorigenic relative potencies (as estimated from the chronic bioassays). Although this was a preliminary investigation, it offers evidence that the short-term tests systems may be of utility in ranking the hazards represented by chemicals which may contribute to increased carcinogenesis in humans as a result of occupational or environmental exposures. 177 refs., 8 tabs.« less

Genogroup IV and VI Canine Noroviruses Interact with Histo-Blood Group Antigens

PubMed Central

Breiman, Adrien; le Pendu, Jacques

2014-01-01

ABSTRACT Human noroviruses (HuNV) are a significant cause of viral gastroenteritis in humans worldwide. HuNV attaches to cell surface carbohydrate structures known as histo-blood group antigens (HBGAs) prior to internalization, and HBGA polymorphism among human populations is closely linked to susceptibility to HuNV. Noroviruses are divided into 6 genogroups, with human strains grouped into genogroups I (GI), II, and IV. Canine norovirus (CNV) is a recently discovered pathogen in dogs, with strains classified into genogroups IV and VI. Whereas it is known that GI to GIII noroviruses bind to HBGAs and GV noroviruses recognize terminal sialic acid residues, the attachment factors for GIV and GVI noroviruses have not been reported. This study sought to determine the carbohydrate binding specificity of CNV and to compare it to the binding specificities of noroviruses from other genogroups. A panel of synthetic oligosaccharides were used to assess the binding specificity of CNV virus-like particles (VLPs) and identified α1,2-fucose as a key attachment factor. CNV VLP binding to canine saliva and tissue samples using enzyme-linked immunosorbent assays (ELISAs) and immunohistochemistry confirmed that α1,2-fucose-containing H and A antigens of the HBGA family were recognized by CNV. Phenotyping studies demonstrated expression of these antigens in a population of dogs. The virus-ligand interaction was further characterized using blockade studies, cell lines expressing HBGAs, and enzymatic removal of candidate carbohydrates from tissue sections. Recognition of HBGAs by CNV provides new insights into the evolution of noroviruses and raises concerns regarding the potential for zoonotic transmission of CNV to humans. IMPORTANCE Infections with human norovirus cause acute gastroenteritis in millions of people each year worldwide. Noroviruses can also affect nonhuman species and are divided into 6 different groups based on their capsid sequences. Human noroviruses in genogroups I and II interact with histo-blood group antigen carbohydrates, bovine noroviruses (genogroup III) interact with alpha-galactosidase (α-Gal) carbohydrates, and murine norovirus (genogroup V) recognizes sialic acids. The canine-specific strains of norovirus are grouped into genogroups IV and VI, and this study is the first to characterize which carbohydrate structures they can recognize. Using canine norovirus virus-like particles, this work shows that representative genogroup IV and VI viruses can interact with histo-blood group antigens. The binding specificity of canine noroviruses is therefore very similar to that of the human norovirus strains classified into genogroups I and II. This raises interesting questions about the evolution of noroviruses and suggests it may be possible for canine norovirus to infect humans. PMID:25008923

Healthy soils healthy people: Unraveling the complexity

USDA-ARS?s Scientific Manuscript database

The linkage between soil and human health is undoubtedly a complex and multidisciplinary issue. The recognition that soil can influence human health is not a novelty; it has been recognized scientifically for decades. However, the advancement in understanding soil health/quality has renewed interest...

Science 101: How Does Speech-Recognition Software Work?

ERIC Educational Resources Information Center

Robertson, Bill

2016-01-01

This column provides background science information for elementary teachers. Many innovations with computer software begin with analysis of how humans do a task. This article takes a look at how humans recognize spoken words and explains the origins of speech-recognition software.

21 CFR 182.3280 - Dilauryl thiodipropionate.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Dilauryl thiodipropionate. 182.3280 Section 182.3280 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION (CONTINUED) SUBSTANCES GENERALLY RECOGNIZED AS SAFE Chemical Preservatives...

21 CFR 184.1695 - Riboflavin.

Code of Federal Regulations, 2011 CFR

2011-04-01

... manufacturing practice conditions of use: (1) The ingredient is used as a nutrient supplement as defined in... Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION (CONTINUED) DIRECT FOOD SUBSTANCES AFFIRMED AS GENERALLY RECOGNIZED AS SAFE Listing of Specific...

Preparation of a Burkholderia mallei Vaccine

DTIC Science & Technology

2002-01-01

Glanders , caused by Burkholderia Mallei , is a significant disease for humans due to the serious nature of the infection. It is recognized that B... Mallei is an organism with tremendous infectivity that poses a significant hazard to humans exposed to aerosols containing this organism.

Evaluating uncertainty to strengthen epidemiologic data for use in human health risk assessments

EPA Science Inventory

Background: There is a recognized need to improve the application of epidemiologic data in human health risk assessment especially for understanding and characterizing risks from environmental and occupational exposures. While most epidemiologic studies result in uncertainty, tec...

Using Human Capital Planning to Predict Future Talent Needs

ERIC Educational Resources Information Center

Ruse, Donald; Jansen, Karen

2008-01-01

Human capital planning is an important tool in predicting future talent needs and sustaining organizational excellence over the long term. This article examines the concept of human capital planning and outlines how institutions can use HCP to identify the type and number of talent needed both now and in the future, recognize and prioritize talent…

The Investment Case for Education and Equity. Executive Summary

ERIC Educational Resources Information Center

UNICEF, 2015

2015-01-01

Education is a human right. The Convention on the Rights of the Child and the Universal Declaration of Human Rights recognize the essential role education plays in human and social development. As stated in article 26 of the Declaration, "Everyone has the right to education. Education shall be free, at least in the elementary and fundamental…

The University Council for Workforce and Human Resource Education: Its History, Purpose, and Activities

ERIC Educational Resources Information Center

Johnson, Scott D.; Martinez, Reynaldo L., Jr.

2009-01-01

This article features the University Council for Workforce and Human Resource Education, a nonprofit organization representing leading United States universities that offer graduate programs in career and technical education (CTE) and human resource development (HRD). The mission of the Council is to be a recognized force in shaping the future of…

Mechanisms of genome evolution of Streptococcus.

PubMed

Andam, Cheryl P; Hanage, William P

2015-07-01

The genus Streptococcus contains 104 recognized species, many of which are associated with human or animal hosts. A globally prevalent human pathogen in this group is Streptococcus pneumoniae (the pneumococcus). While being a common resident of the upper respiratory tract, it is also a major cause of otitis media, pneumonia, bacteremia and meningitis, accounting for a high burden of morbidity and mortality worldwide. Recent findings demonstrate the importance of recombination and selection in driving the population dynamics and evolution of different pneumococcal lineages, allowing them to successfully evade the impacts of selective pressures such as vaccination and antibiotic treatment. We highlight the ability of pneumococci to respond to these pressures through processes including serotype replacement, capsular switching and horizontal gene transfer (HGT) of antibiotic resistance genes. The challenge in controlling this pathogen also lies in the exceptional genetic and phenotypic variation among different pneumococcal lineages, particularly in terms of their pathogenicity and resistance to current therapeutic strategies. The widespread use of pneumococcal conjugate vaccines, which target only a small subset of the more than 90 pneumococcal serotypes, provides us with a unique opportunity to elucidate how the processes of selection and recombination interact to generate a remarkable level of plasticity and heterogeneity in the pneumococcal genome. These processes also play an important role in the emergence and spread of multi-resistant strains, which continues to pose a challenge in disease control and/or eradication. The application of population of genomic approaches at different spatial and temporal scales will help improve strategies to control this global pathogen, and potentially other pathogenic streptococci. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

Expression and purification of native and functional influenza A virus matrix 2 proton selective ion channel.

PubMed

Desuzinges Mandon, Elodie; Traversier, Aurélien; Champagne, Anne; Benier, Lorraine; Audebert, Stéphane; Balme, Sébastien; Dejean, Emmanuel; Rosa Calatrava, Manuel; Jawhari, Anass

2017-03-01

Influenza A virus displays one of the highest infection rates of all human viruses and therefore represents a severe human health threat associated with an important economical challenge. Influenza matrix protein 2 (M2) is a membrane protein of the viral envelope that forms a proton selective ion channel. Here we report the expression and native isolation of full length active M2 without mutations or fusions. The ability of the influenza virus to efficiently infect MDCK cells was used to express native M2 protein. Using a Calixarene detergents/surfactants based approach; we were able to solubilize most of M2 from the plasma membrane and purify it. The tetrameric form of native M2 was maintained during the protein preparation. Mass spectrometry shows that M2 was phosphorylated in its cytoplasmic tail (serine 64) and newly identifies an acetylation of the highly conserved Lysine 60. ELISA shows that solubilized and purified M2 was specifically recognized by M2 antibody MAB65 and was able to displace the antibody from M2 MDCK membranes. Using a bilayer voltage clamp measurement assay, we demonstrate a pH dependent proton selective ion channel activity. The addition of the M2 ion channel blocker amantadine allows a total inhibition of the channel activity, illustrating therefore the specificity of purified M2 activity. Taken together, this work shows the production and isolation of a tetrameric and functional native M2 ion channel that will pave the way to structural and functional characterization of native M2, conformational antibody development, small molecules compounds screening towards vaccine treatment. Copyright © 2016 Elsevier Inc. All rights reserved.

High-Dose Mannose-Binding Lectin Therapy for Ebola Virus Infection

DTIC Science & Technology

2010-06-01

viruses . N-glycosylation of viral envelopes is an important such target shared between in- fluenza, HIV, HCV, West Nile virus , SARS-CoV, Hendra virus ...host cells. Therefore, MBL preferentially recognizes glycosylated viruses including influenza virus , human immunodeficiency virus , severe acute...respiratory syndrome coronovirus (SARS-CoV), Ebola virus , and Marburg virus . It also recognizes many glycosylated gram- positive and gram-negative bacteria [1

Injuries due to human and animal aggression in humans.

PubMed

Łabęcka, Marzena; Lorkiewicz-Muszyńska, Dorota E; Przystańska, Agnieszka; Kondrusiewicz, Krzysztof

2013-01-01

People breed animals, professionally take care of them, and work with them. To live with animals, however, it is necessary to know their behaviour and habits, as well as fears. Ignorance of this knowledge may lead to tragedy for the victim (a person), as well as for the beast (animal). Then, nobody cares whether the animal behaved itself or not in accordance with its nature. The aim of the presented study is to compare the rate of animal aggression in relation to cases of documented aggression towards humans. The victims were investigated according to the age, gender and types of injuries caused by animal bites. The protocols of autopsies (2,218) and medical-legal examinations (4,569) performed from 2004-2009 in the Department of Forensic Sciences in Poznań were analyzed. The selected data was studied using Microsoft Office Excel 2007 for Windows. Analysis revealed the presence of animal bite injuries in less than 1% of the deceased victims of aggression. The number of individuals who died as a result of animal bites varied from 1-4 a year, and in all cases these were postmortem injuries. Analysis of injuries among surviving victims of aggression showed animal bite injuries were present in 41 out of 4,569 victims, almost equally among males and females. Moreover, in 25 victims the bite injuries recognized as human were found. The majority of animal bites occurred in adults. The medium injuries were the most frequent in the animal bite victims. Animal aggression is a marginal problem considering all cases of aggression towards humans. In contrast to the aggression of humans towards other humans, this is a very rare cause of human death or even major injury.

Detection of Signal Regulatory Protein α in Saimiri sciureus (Squirrel Monkey) by Anti-Human Monoclonal Antibody

PubMed Central

de Souza, Hugo Amorim dos Santos; Costa-Correa, Edmar Henrique; Bianco-Junior, Cesare; Andrade, Márcia Cristina Ribeiro; Lima-Junior, Josué da Costa; Pratt-Riccio, Lilian Rose; Daniel-Ribeiro, Cláudio Tadeu; Totino, Paulo Renato Rivas

2017-01-01

Non-human primates (NHP) are suitable models for studying different aspects of the human system, including pathogenesis and protective immunity to many diseases. However, the lack of specific immunological reagents for neo-tropical monkeys, such as Saimiri sciureus, is still a major factor limiting studies in these models. An alternative strategy to circumvent this obstacle has been the selection of immunological reagents directed to humans, which present cross-reactivity with NHP molecules. In this context and considering the key role of inhibitory immunoreceptors—such as the signal regulatory protein α (SIRPα)—in the regulation of immune responses, in the present study, we attempted to evaluate the ability of anti-human SIRPα monoclonal antibodies to recognize SIRPα in antigen-presenting S. sciureus peripheral blood mononuclear cells (PBMC). As shown by flow cytometry analysis, the profile of anti-SIRPα staining as well as the levels of SIRPα-positive cells in PBMC from S. sciureus were similar to those observed in human PBMC. Furthermore, using anti-SIRPα monoclonal antibody, it was possible to detect a decrease of the SIRPα levels on surface of S. sciureus cells after in vitro stimulation with lipopolysaccharides. Finally, using computed-based analysis, we observed a high degree of conservation of SIRPα across six species of primates and the presence of shared epitopes in the extracellular domain between humans and Saimiri genus that could be targeted by antibodies. In conclusion, we have identified a commercially available anti-human monoclonal antibody that is able to detect SIRPα of S. sciureus monkeys and that, therefore, can facilitate the study of the immunomodulatory role of SIRPα when S. sciureus is used as a model. PMID:29312325

Human Group C Rotavirus VP8*s Recognize Type A Histo-Blood Group Antigens as Ligands.

PubMed

Sun, Xiaoman; Wang, Lihong; Qi, Jianxun; Li, Dandi; Wang, Mengxuan; Cong, Xin; Peng, Ruchao; Chai, Wengang; Zhang, Qing; Wang, Hong; Wen, Hongling; Gao, George F; Tan, Ming; Duan, Zhaojun

2018-06-01

Group/species C rotaviruses (RVCs) have been identified as important pathogens of acute gastroenteritis (AGE) in children, family-based outbreaks, as well as animal infections. However, little is known regarding their host-specific interaction, infection, and pathogenesis. In this study, we performed serial studies to characterize the function and structural features of a human G4P[2] RVC VP8* that is responsible for the host receptor interaction. Glycan microarrays demonstrated that the human RVC VP8* recognizes type A histo-blood group antigens (HBGAs), which was confirmed by synthetic glycan-/saliva-based binding assays and hemagglutination of red blood cells, establishing a paradigm of RVC VP8*-glycan interactions. Furthermore, the high-resolution crystal structure of the human RVC VP8* was solved, showing a typical galectin-like structure consisting of two β-sheets but with significant differences from cogent proteins of group A rotaviruses (RVAs). The VP8* in complex with a type A trisaccharide displays a novel ligand binding site that consists of a particular set of amino acid residues of the C-D, G-H, and K-L loops. RVC VP8* interacts with type A HBGAs through a unique mechanism compared with that used by RVAs. Our findings shed light on the host-virus interaction and the coevolution of RVCs and will facilitate the development of specific antivirals and vaccines. IMPORTANCE Group/species C rotaviruses (RVCs), members of Reoviridae family, infect both humans and animals, but our knowledge about the host factors that control host susceptibility and specificity is rudimentary. In this work, we characterized the glycan binding specificity and structural basis of a human RVC that recognizes type A HBGAs. We found that human RVC VP8*, the rotavirus host ligand binding domain that shares only ∼15% homology with the VP8* domains of RVAs, recognizes type A HBGA at an as-yet-unknown glycan binding site through a mechanism distinct from that used by RVAs. Our new advancements provide insights into RVC-cell attachment, the critical step of virus infection, which will in turn help the development of control and prevention strategies against RVs. Copyright © 2018 American Society for Microbiology.

The Intolerance of Regulatory Sequence to Genetic Variation Predicts Gene Dosage Sensitivity

PubMed Central

Wang, Quanli; Halvorsen, Matt; Han, Yujun; Weir, William H.; Allen, Andrew S.; Goldstein, David B.

2015-01-01

Noncoding sequence contains pathogenic mutations. Yet, compared with mutations in protein-coding sequence, pathogenic regulatory mutations are notoriously difficult to recognize. Most fundamentally, we are not yet adept at recognizing the sequence stretches in the human genome that are most important in regulating the expression of genes. For this reason, it is difficult to apply to the regulatory regions the same kinds of analytical paradigms that are being successfully applied to identify mutations among protein-coding regions that influence risk. To determine whether dosage sensitive genes have distinct patterns among their noncoding sequence, we present two primary approaches that focus solely on a gene’s proximal noncoding regulatory sequence. The first approach is a regulatory sequence analogue of the recently introduced residual variation intolerance score (RVIS), termed noncoding RVIS, or ncRVIS. The ncRVIS compares observed and predicted levels of standing variation in the regulatory sequence of human genes. The second approach, termed ncGERP, reflects the phylogenetic conservation of a gene’s regulatory sequence using GERP++. We assess how well these two approaches correlate with four gene lists that use different ways to identify genes known or likely to cause disease through changes in expression: 1) genes that are known to cause disease through haploinsufficiency, 2) genes curated as dosage sensitive in ClinGen’s Genome Dosage Map, 3) genes judged likely to be under purifying selection for mutations that change expression levels because they are statistically depleted of loss-of-function variants in the general population, and 4) genes judged unlikely to cause disease based on the presence of copy number variants in the general population. We find that both noncoding scores are highly predictive of dosage sensitivity using any of these criteria. In a similar way to ncGERP, we assess two ensemble-based predictors of regional noncoding importance, ncCADD and ncGWAVA, and find both scores are significantly predictive of human dosage sensitive genes and appear to carry information beyond conservation, as assessed by ncGERP. These results highlight that the intolerance of noncoding sequence stretches in the human genome can provide a critical complementary tool to other genome annotation approaches to help identify the parts of the human genome increasingly likely to harbor mutations that influence risk of disease. PMID:26332131

Recommendations for genetic variation data capture in developing countries to ensure a comprehensive worldwide data collection.

PubMed

Patrinos, George P; Al Aama, Jumana; Al Aqeel, Aida; Al-Mulla, Fahd; Borg, Joseph; Devereux, Andrew; Felice, Alex E; Macrae, Finlay; Marafie, Makia J; Petersen, Michael B; Qi, Ming; Ramesar, Rajkumar S; Zlotogora, Joel; Cotton, Richard G H

2011-01-01

Developing countries have significantly contributed to the elucidation of the genetic basis of both common and rare disorders, providing an invaluable resource of cases due to large family sizes, consanguinity, and potential founder effects. Moreover, the recognized depth of genomic variation in indigenous African populations, reflecting the ancient origins of humanity on the African continent, and the effect of selection pressures on the genome, will be valuable in understanding the range of both pathological and nonpathological variations. The involvement of these populations in accurately documenting the extant genetic heterogeneity is more than essential. Developing nations are regarded as key contributors to the Human Variome Project (HVP; http://www.humanvariomeproject.org), a major effort to systematically collect mutations that contribute to or cause human disease and create a cyber infrastructure to tie databases together. However, biomedical research has not been the primary focus in these countries even though such activities are likely to produce economic and health benefits for all. Here, we propose several recommendations and guidelines to facilitate participation of developing countries in genetic variation data documentation, ensuring an accurate and comprehensive worldwide data collection. We also summarize a few well-coordinated genetic data collection initiatives that would serve as paradigms for similar projects.

The point-of-care colorimetric detection of the biomarker of phenylamine in the human urine based on Tb3+ functionalized metal-organic framework.

PubMed

Qin, Si-Jia; Yan, Bing

2018-07-05

Phenylamine has been recognized as one of the most important industrially relevant ingredient and a crucial intermediate in chemical products. Yet, its internal exposure detection in human remains largely elusive due to the lack of potent monitoring method. Hereby this issue is addressed with a probe based on lanthanide functionalized organic-inorganic hybrid material Al(OH)(bpydc) (1) through post-synthetically modified metal-organic framework. The as-synthesized Tb 3+ @1 exhibits the strong luminescence of Tb 3+ originated from efficient energy transfer from the ligand, which can sense the biological metabolite p-aminophenol (PAP) of the phenylamine in the human urine. Linear correlation between the integrated fluorescence intensity and the concentration of PAP was investigated, enabling quantitative analysis of PAP in physiologically ranges (0.005-5 mg mL -1 ) with low detection limit (5 μg mL -1 ). This probe demonstrates excellent sensitivity, high selectivity, good reusability and quick response to PAP. Furthermore, a simple and rapid smartphone-based medical portable test paper was developed, whose quantitative color change can be easily distinguished visually. Hence, the PAP sensing platform can serve as a potential diagnostic tool for home monitoring of PAP. Copyright © 2018 Elsevier B.V. All rights reserved.

Generation and Characterization of Anti-CD34 Monoclonal Antibodies that React with Hematopoietic Stem Cells

PubMed Central

Aghebati Maleki, Leili; Majidi, Jafar; Baradaran, Behzad; Movassaghpour, Aliakbar; Abdolalizadeh, Jalal

2014-01-01

CD34 is a type I membrane protein with a molecular mass of approximately 110 kDa. This antigen is associated with human hematopoietic progenitor cells and is a differentiation stage-specific leukocyte antigen. In this study we have generated and characterized monoclonal antibodies (mAbs) directed against a CD34 marker. Mice were immunized with two keyhole lympet hemocyanin (KLH)-conjugated CD34 peptides. Fused cells were grown in hypoxanthine, aminopterine and thymidine (HAT) selective medium and cloned by the limiting dilution (L.D) method. Several monoclones were isolated by three rounds of limited dilutions. From these, we chose stable clones that presented sustained antibody production for subsequent characterization. Antibodies were tested for their reactivity and specificity to recognize the CD34 peptides and further screened by enzyme-linked immunosorbent assay (ELISA) and Western blotting analyses. One of the mAbs (3D5) was strongly reactive against the CD34 peptide and with native CD34 from human umbilical cord blood cells (UCB) in ELISA and Western blotting analyses. The results have shown that this antibody is highly specific and functional in biomedical applications such as ELISA and Western blot assays. This monoclonal antibodies (mAb) can be a useful tool for isolation and purification of human hematopoietic stem cells (HSCs). PMID:24611141

Human behavioral assessments in current research of Parkinson's disease.

PubMed

Asakawa, Tetsuya; Fang, Huan; Sugiyama, Kenji; Nozaki, Takao; Kobayashi, Susumu; Hong, Zhen; Suzuki, Katsuaki; Mori, Norio; Yang, Yilin; Hua, Fei; Ding, Guanghong; Wen, Guoqiang; Namba, Hiroki; Xia, Ying

2016-09-01

Parkinson's disease (PD) is traditionally classified as a movement disorder because patients mainly complain about motor symptoms. Recently, non-motor symptoms of PD have been recognized by clinicians and scientists as early signs of PD, and they are detrimental factors in the quality of life in advanced PD patients. It is crucial to comprehensively understand the essence of behavioral assessments, from the simplest measurement of certain symptoms to complex neuropsychological tasks. We have recently reviewed behavioral assessments in PD research with animal models (Asakawa et al., 2016). As a companion volume, this article will systematically review the behavioral assessments of motor and non-motor PD symptoms of human patients in current research. The major aims of this article are: (1) promoting a comparative understanding of various behavioral assessments in terms of the principle and measuring indexes; (2) addressing the major strengths and weaknesses of these behavioral assessments for a better selection of tasks/tests in order to avoid biased conclusions due to inappropriate assessments; and (3) presenting new concepts regarding the development of wearable devices and mobile internet in future assessments. In conclusion we emphasize the importance of improving the assessments for non-motor symptoms because of their complex and unique mechanisms in human PD brains. Copyright © 2016 Elsevier Ltd. All rights reserved.

The role of alternative splicing coupled to nonsense-mediated mRNA decay in human disease.

PubMed

da Costa, Paulo J; Menezes, Juliane; Romão, Luísa

2017-10-01

Alternative pre-mRNA splicing (AS) affects gene expression as it generates proteome diversity. Nonsense-mediated mRNA decay (NMD) is a surveillance pathway that recognizes and selectively degrades mRNAs carrying premature translation-termination codons (PTCs), preventing the production of truncated proteins that could result in disease. Several studies have also implicated NMD in the regulation of steady-state levels of physiological mRNAs. In addition, it is known that several regulated AS events do not lead to generation of protein products, as they lead to transcripts that carry PTCs and thus, they are committed to NMD. Indeed, an estimated one-third of naturally occurring, alternatively spliced mRNAs is targeted for NMD, being AS coupled to NMD (AS-NMD) an efficient strategy to regulate gene expression. In this review, we will focus on how AS mechanism operates and how can be coupled to NMD to fine-tune gene expression levels. Furthermore, we will demonstrate the physiological significance of the interplay among AS and NMD in human disease, such as cancer and neurological disorders. The understanding of how AS-NMD orchestrates expression of vital genes is of utmost importance for the advance in diagnosis, prognosis and treatment of many human disorders. Copyright © 2017 Elsevier Ltd. All rights reserved.

Who Are the Okinawans? Ancestry, Genome Diversity, and Implications for the Genetic Study of Human Longevity From a Geographically Isolated Population

PubMed Central

Hsueh, Wen-Chi; He, Qimei; Willcox, D. Craig; Nievergelt, Caroline M.; Donlon, Timothy A.; Kwok, Pui-Yan; Suzuki, Makoto; Willcox, Bradley J.

2014-01-01

Isolated populations have advantages for genetic studies of longevity from decreased haplotype diversity and long-range linkage disequilibrium. This permits smaller sample sizes without loss of power, among other utilities. Little is known about the genome of the Okinawans, a potential population isolate, recognized for longevity. Therefore, we assessed genetic diversity, structure, and admixture in Okinawans, and compared this with Caucasians, Chinese, Japanese, and Africans from HapMap II, genotyped on the same Affymetrix GeneChip Human Mapping 500K array. Principal component analysis, haplotype coverage, and linkage disequilibrium decay revealed a distinct Okinawan genome—more homogeneity, less haplotype diversity, and longer range linkage disequilibrium. Population structure and admixture analyses utilizing 52 global reference populations from the Human Genome Diversity Cell Line Panel demonstrated that Okinawans clustered almost exclusively with East Asians. Sibling relative risk (λs) analysis revealed that siblings of Okinawan centenarians have 3.11 times (females) and 3.77 times (males) more likelihood of centenarianism. These findings suggest that Okinawans are genetically distinct and share several characteristics of a population isolate, which are prone to develop extreme phenotypes (eg, longevity) from genetic drift, natural selection, and population bottlenecks. These data support further exploration of genetic influence on longevity in the Okinawans. PMID:24444611

The influence of nationality on the accuracy of face and voice recognition.

PubMed

Doty, N D

1998-01-01

Sixty English and U.S. citizens were tested to determine the effect of nationality on accuracy in recognizing previously witnessed faces and voices. Subjects viewed a frontal facial photograph and were then asked to select that face from a set of 10 oblique facial photographs. Subjects listened to a recorded voice and were then asked to select the same voice from a set of 10 voice recordings. This process was repeated 7 more times, such that subjects identified a male and female face and voice from England, France, Belize, and the United States. Subjects demonstrated better accuracy recognizing the faces and voices of their own nationality. Subgoups analysis further supported the other-nationality effect as well as the previously documented other-race effect.

The science and fiction of emerging rickettsioses.

PubMed

Paddock, Christopher D

2009-05-01

As newly recognized rickettsial diseases and rickettsial pathogens increase in scope and magnitude, several elements related to the concept of emerging rickettsioses deserve consideration. Newly identified rickettsiae may be mildly pathogenic, or perhaps even nonpathogenic, and have little direct impact on human or animal health, yet nonetheless wield considerable influence on the epidemiology and ecology of historically recognized diseases. In this context "new" rickettsioses provide a lens through which "old" rickettsioses are more accurately represented. Predicting pathogen from nonpathogen is not an exact science, particularly as so few rickettsiae have been broadly accepted as nonpathogenic by contemporary rickettsiologists. However, various factors relating to specific physiologic requirements and molecular machinery of the particular rickettsia, as well as characteristics of its invertebrate host that either position or exclude the rickettsia from infecting a human host, must be considered. Close inspection of mild or atypical forms of historically recognized rickettsioses and a greater emphasis on culture- and molecular-based diagnostic techniques are the keys to identifying future rickettsial agents of disease.

Human NOD2 Recognizes Structurally Unique Muramyl Dipeptides from Mycobacterium leprae

PubMed Central

Schenk, Mirjam; Mahapatra, Sebabrata; Le, Phuonganh; Kim, Hee Jin; Choi, Aaron W.; Brennan, Patrick J.; Belisle, John T.

2016-01-01

The innate immune system recognizes microbial pathogens via pattern recognition receptors. One such receptor, NOD2, via recognition of muramyl dipeptide (MDP), triggers a distinct network of innate immune responses, including the production of interleukin-32 (IL-32), which leads to the differentiation of monocytes into dendritic cells (DC). NOD2 has been implicated in the pathogenesis of human leprosy, yet it is not clear whether Mycobacterium leprae, which has a distinct MDP structure, can activate this pathway. We investigated the effect of MDP structure on the innate immune response, finding that infection of monocytes with M. leprae induces IL-32 and DC differentiation in a NOD2-dependent manner. The presence of the proximal l-Ala instead of Gly in the common configuration of the peptide side chain of M. leprae did not affect recognition by NOD2 or cytokine production. Furthermore, amidation of the d-Glu residue did not alter NOD2 activation. These data provide experimental evidence that NOD2 recognizes naturally occurring structural variants of MDP. PMID:27297389

Spatial acoustic radiation of respiratory sounds for sleep evaluation.

PubMed

Shabtai, Noam R; Zigel, Yaniv

2017-09-01

Body posture has an effect on sleeping quality and breathing disorders and therefore it is important to be recognized for the completion of the sleep evaluation process. Since humans have a directional acoustic radiation pattern, it is hypothesized that microphone arrays can be used to recognize different body postures, which is highly practical for sleep evaluation applications that already measure respiratory sounds using distant microphones. Furthermore, body posture may have an effect on distant microphone measurement; hence, the measurement can be compensated if the body posture is correctly recognized. A spherical harmonics decomposition approach to the spatial acoustic radiation is presented, assuming an array of eight microphones in a medium-sized audiology booth. The spatial sampling and reconstruction of the radiation pattern is discussed, and a final setup for the microphone array is recommended. A case study is shown using recorded segments of snoring and breathing sounds of three human subjects in three body postures in a silent but not anechoic audiology booth.

Characterization of the UGA-recoding and SECIS-binding activities of SECIS-binding protein 2.

PubMed

Bubenik, Jodi L; Miniard, Angela C; Driscoll, Donna M

2014-01-01

Selenium, a micronutrient, is primarily incorporated into human physiology as selenocysteine (Sec). The 25 Sec-containing proteins in humans are known as selenoproteins. Their synthesis depends on the translational recoding of the UGA stop codon to allow Sec insertion. This requires a stem-loop structure in the 3' untranslated region of eukaryotic mRNAs known as the Selenocysteine Insertion Sequence (SECIS). The SECIS is recognized by SECIS-binding protein 2 (SBP2) and this RNA:protein interaction is essential for UGA recoding to occur. Genetic mutations cause SBP2 deficiency in humans, resulting in a broad set of symptoms due to differential effects on individual selenoproteins. Progress on understanding the different phenotypes requires developing robust tools to investigate SBP2 structure and function. In this study we demonstrate that SBP2 protein produced by in vitro translation discriminates among SECIS elements in a competitive UGA recoding assay and has a much higher specific activity than bacterially expressed protein. We also show that a purified recombinant protein encompassing amino acids 517-777 of SBP2 binds to SECIS elements with high affinity and selectivity. The affinity of the SBP2:SECIS interaction correlated with the ability of a SECIS to compete for UGA recoding activity in vitro. The identification of a 250 amino acid sequence that mediates specific, selective SECIS-binding will facilitate future structural studies of the SBP2:SECIS complex. Finally, we identify an evolutionarily conserved core cysteine signature in SBP2 sequences from the vertebrate lineage. Mutation of multiple, but not single, cysteines impaired SECIS-binding but did not affect protein localization in cells.

Meiotic recombination generates rich diversity in NK cell receptor genes, alleles, and haplotypes

PubMed Central

Norman, Paul J.; Abi-Rached, Laurent; Gendzekhadze, Ketevan; Hammond, John A.; Moesta, Achim K.; Sharma, Deepti; Graef, Thorsten; McQueen, Karina L.; Guethlein, Lisbeth A.; Carrington, Christine V.F.; Chandanayingyong, Dasdayanee; Chang, Yih-Hsin; Crespí, Catalina; Saruhan-Direskeneli, Güher; Hameed, Kamran; Kamkamidze, Giorgi; Koram, Kwadwo A.; Layrisse, Zulay; Matamoros, Nuria; Milà, Joan; Park, Myoung Hee; Pitchappan, Ramasamy M.; Ramdath, D. Dan; Shiau, Ming-Yuh; Stephens, Henry A.F.; Struik, Siske; Tyan, Dolly; Verity, David H.; Vaughan, Robert W.; Davis, Ronald W.; Fraser, Patricia A.; Riley, Eleanor M.; Ronaghi, Mostafa; Parham, Peter

2009-01-01

Natural killer (NK) cells contribute to the essential functions of innate immunity and reproduction. Various genes encode NK cell receptors that recognize the major histocompatibility complex (MHC) Class I molecules expressed by other cells. For primate NK cells, the killer-cell immunoglobulin-like receptors (KIR) are a variable and rapidly evolving family of MHC Class I receptors. Studied here is KIR3DL1/S1, which encodes receptors for highly polymorphic human HLA-A and -B and comprises three ancient allelic lineages that have been preserved by balancing selection throughout human evolution. While the 3DS1 lineage of activating receptors has been conserved, the two 3DL1 lineages of inhibitory receptors were diversified through inter-lineage recombination with each other and with 3DS1. Prominent targets for recombination were D0-domain polymorphisms, which modulate enhancer function, and dimorphism at position 283 in the D2 domain, which influences inhibitory function. In African populations, unequal crossing over between the 3DL1 and 3DL2 genes produced a deleted KIR haplotype in which the telomeric “half” was reduced to a single fusion gene with functional properties distinct from its 3DL1 and 3DL2 parents. Conversely, in Eurasian populations, duplication of the KIR3DL1/S1 locus by unequal crossing over has enabled individuals to carry and express alleles of all three KIR3DL1/S1 lineages. These results demonstrate how meiotic recombination combines with an ancient, preserved diversity to create new KIR phenotypes upon which natural selection acts. A consequence of such recombination is to blur the distinction between alleles and loci in the rapidly evolving human KIR gene family. PMID:19411600

Human antibodies against spores of the genus Bacillus: a model study for detection of and protection against anthrax and the bioterrorist threat.

PubMed

Zhou, Bin; Wirsching, Peter; Janda, Kim D

2002-04-16

A naive, human single-chain Fv (scFv) phage-display library was used in bio-panning against live, native spores of Bacillus subtilis IFO 3336 suspended in solution. A direct in vitro panning and enzyme-linked immunosorbent assay-based selection afforded a panel of nine scFv-phage clones of which two, 5B and 7E, were chosen for further study. These two clones differed in their relative specificity and affinity for spores of B. subtilis IFO 3336 vs. a panel of spores from 11 other Bacillus species/strains. A variety of enzyme-linked immunosorbent assay protocols indicated these scFv-phage clones recognized different spore epitopes. Notably, some spore epitopes markedly changed between the free and microtiter-plate immobilized state as revealed by antibody-phage binding. An additional library selection procedure also was examined by constructing a Fab chain-shuffled sublibrary from the nine positive clones and by using a subtractive panning strategy to remove crossreactivity with B. licheniformis 5A24. The Fab-phage clone 52 was improved compared with 5B and was comparable to 7E in binding B. subtilis IFO 3336 vs. B. licheniformis 5A24, yet showed a distinctive crossreactivity pattern with other spores. We also developed a method to directly detect individual spores by using fluorescently labeled antibody-phage. Finally, a variety of "powders" that might be used in deploying spores of B. anthracis were examined for antibody-phage binding. The strategies described provide a foundation to discover human antibodies specific for native spores of B. anthracis that can be developed as diagnostic and therapeutic reagents.

Multimodal Wireless Sensor Network-Based Ambient Assisted Living in Real Homes with Multiple Residents

PubMed Central

Tunca, Can; Alemdar, Hande; Ertan, Halil; Incel, Ozlem Durmaz; Ersoy, Cem

2014-01-01

Human activity recognition and behavior monitoring in a home setting using wireless sensor networks (WSNs) provide a great potential for ambient assisted living (AAL) applications, ranging from health and wellbeing monitoring to resource consumption monitoring. However, due to the limitations of the sensor devices, challenges in wireless communication and the challenges in processing large amounts of sensor data in order to recognize complex human activities, WSN-based AAL systems are not effectively integrated in the home environment. Additionally, given the variety of sensor types and activities, selecting the most suitable set of sensors in the deployment is an important task. In order to investigate and propose solutions to such challenges, we introduce a WSN-based multimodal AAL system compatible for homes with multiple residents. Particularly, we focus on the details of the system architecture, including the challenges of sensor selection, deployment, networking and data collection and provide guidelines for the design and deployment of an effective AAL system. We also present the details of the field study we conducted, using the systems deployed in two different real home environments with multiple residents. With these systems, we are able to collect ambient sensor data from multiple homes. This data can be used to assess the wellbeing of the residents and identify deviations from everyday routines, which may be indicators of health problems. Finally, in order to elaborate on the possible applications of the proposed AAL system and to exemplify directions for processing the collected data, we provide the results of several human activity inference experiments, along with examples on how such results could be interpreted. We believe that the experiences shared in this work will contribute towards accelerating the acceptance of WSN-based AAL systems in the home setting. PMID:24887044

Characterization of an Adhesion Molecule that Mediates Leukocyte Rolling on 24 h Cytokine- or Lipopolysaccharide-stimulated Bovine Endothelial Cells under Flow Conditions

PubMed Central

Jutila, Mark A.; Wilson, Eric; Kurk, Sandy

1997-01-01

Bovine γ/δ T cells and neutrophils roll on 24 h cytokine- or lipopolysaccharide-stimulated bovine fetal umbilical cord endothelial cells in assays done under physiological flow. An antibody directed against E- and L-selectin has minimal blocking effect on this rolling interaction. mAbs were raised against the stimulated bovine endothelial cells and screened for inhibition of γ/δ T cell rolling. One mAb (GR113) was identified that recognizes an antigen (GR antigen) selectively expressed by stimulated bovine endothelial cells isolated from fetal umbilical cord, mesenteric lymph nodes, and aorta. GR113 blocked bovine γ/δ T cell as well as neutrophil rolling on the 24 h-activated endothelial cells. The GR antigen was constitutively expressed at low levels on the cell surface of platelets and its expression was not upregulated after stimulation of these cells with thrombin or phorbol myristate acetate. However, stimulated platelets released a soluble, functionally active form of the molecule that selectively bound in solution to γ/δ T cells in a mixed lymphocyte preparation. GR113 mAb blocked the binding of the soluble platelet molecule to the γ/δ T cells. Soluble GR antigen also bound a subset of human lymphocytes. Cutaneous lymphocyte-associated antigen (CLA) bright human lymphocytes exhibited the greatest capacity to bind the GR antigen, though CLA was not required for binding. Subsets of both human CD4 and CD8 T cells bound the GR antigen. Immunoprecipitation experiments showed the GR antigen to be 110-120 kD M r. The binding of soluble GR antigen was inhibited by EDTA and O-sialoglycoprotease, but not neuraminidase treatment of the target cells. PMID:9362530

Multimodal wireless sensor network-based ambient assisted living in real homes with multiple residents.

PubMed

Tunca, Can; Alemdar, Hande; Ertan, Halil; Incel, Ozlem Durmaz; Ersoy, Cem

2014-05-30

Human activity recognition and behavior monitoring in a home setting using wireless sensor networks (WSNs) provide a great potential for ambient assisted living (AAL) applications, ranging from health and wellbeing monitoring to resource consumption monitoring. However, due to the limitations of the sensor devices, challenges in wireless communication and the challenges in processing large amounts of sensor data in order to recognize complex human activities, WSN-based AAL systems are not effectively integrated in the home environment. Additionally, given the variety of sensor types and activities, selecting the most suitable set of sensors in the deployment is an important task. In order to investigate and propose solutions to such challenges, we introduce a WSN-based multimodal AAL system compatible for homes with multiple residents. Particularly, we focus on the details of the system architecture, including the challenges of sensor selection, deployment, networking and data collection and provide guidelines for the design and deployment of an effective AAL system. We also present the details of the field study we conducted, using the systems deployed in two different real home environments with multiple residents. With these systems, we are able to collect ambient sensor data from multiple homes. This data can be used to assess the wellbeing of the residents and identify deviations from everyday routines, which may be indicators of health problems. Finally, in order to elaborate on the possible applications of the proposed AAL system and to exemplify directions for processing the collected data, we provide the results of several human activity inference experiments, along with examples on how such results could be interpreted. We believe that the experiences shared in this work will contribute towards accelerating the acceptance of WSN-based AAL systems in the home setting.

Reprogramming Microbes for the Remote Detection of Environmental Threats

DTIC Science & Technology

2013-10-15

Riboswitches consist of an aptamer that recognizes the ligand and an expression platform that couples ligand binding to a change in gene expression. Using in...vitro selection, it is possible to screen large (~10^13 member) libraries of RNA sequences to discover new aptamers . However, limitations in...consist of an aptamer that recognizes the ligand and an expression platform that couples ligand binding to a change in gene expression. Using in

Domestication Does Not Explain the Presence of Inequity Aversion in Dogs.

PubMed

Essler, Jennifer L; Marshall-Pescini, Sarah; Range, Friederike

2017-06-19

Sensitivity to inequity is thought to be an important mechanism for recognizing undesirable cooperative partners and thus crucial for the evolution of human cooperation [1]. This link may not be unique to humans, as cooperative non-human primates also react to unequal outcomes [2], whereas non-cooperative species do not [3]. Although this hypothesis has not been tested in non-primate species, studies revealed that pet dogs show a limited form of inequity aversion, responding to reward, but not quality inequity [4-6]. It has been proposed that this primitive form of inequity aversion was selected for during domestication and thus absent in their ancestors, wolves. Alternatively, wolves, which hunt, raise pups, and defend their territory cooperatively, are similarly inequity averse as non-human primates, or at least to the same degree as pet dogs. Testing similarly raised and kept pack-living dogs and wolves, we found both to be inequity averse when their partner was being rewarded but they were not for performing the same action. Additionally, both wolves and dogs reacted to receiving a lower-quality reward than their partner. These results suggest that the inequity response found in pack-living dogs and wolves is comparable to that observed in non-human primates; results from studies on pet dogs may be confounded by the dogs' relationship with humans. Consequently, our results suggest that inequity aversion was present already in the common-probably cooperative-ancestor of wolves and dogs and thus support the hypothesis of a close link of cooperation and inequity aversion. Copyright © 2017 Elsevier Ltd. All rights reserved.

The human right to water: the importance of domestic and productive water rights.

PubMed

Hall, Ralph P; Van Koppen, Barbara; Van Houweling, Emily

2014-12-01

The United Nations (UN) Universal Declaration of Human Rights engenders important state commitments to respect, fulfill, and protect a broad range of socio-economic rights. In 2010, a milestone was reached when the UN General Assembly recognized the human right to safe and clean drinking water and sanitation. However, water plays an important role in realizing other human rights such as the right to food and livelihoods, and in realizing the Convention on the Elimination of All Forms of Discrimination against Women. These broader water-related rights have been recognized but have not yet been operationalized. This paper unravels these broader water-related rights in a more holistic interpretation of existing international human rights law. By focusing on an emerging approach to water services provision--known as 'domestic-plus' services--the paper argues how this approach operationalizes a comprehensive range of socio-economic rights in rural and peri-urban areas. Domestic-plus services provide water for domestic and productive uses around homesteads, which challenges the widespread practice in the public sector of planning and designing water infrastructure for a single-use. Evidence is presented to show that people in rural communities are already using their water supplies planned for domestic uses to support a wide range of productive activities. Domestic-plus services recognize and plan for these multiple-uses, while respecting the priority for clean and safe drinking water. The paper concludes that domestic-plus services operationalize the obligation to progressively fulfill a comprehensive range of indivisible socio-economic rights in rural and peri-urban areas.