Basic and clinical immunology of Siglecs

Siglecs are cell-surface proteins found primarily on hematopoietic cells. By definition, they are members of the immunoglobulin gene super-family and bind sialic acid. Most contain cytoplasmic tyrosine motifs implicated in cell signaling. This review will first summarize characteristics common and unique to Siglecs, followed by a discussion of each human Siglec in numerical order, mentioning in turn its closest murine ortholog or paralog. Each section will describe its pattern of cellular expression, latest known immune functions, ligands, and signaling pathways, with the focus being predominantly on CD33-related Siglecs. Potential clinical and therapeutic implications of each Siglec will also be covered.

Linear and Piecewise Functions

This morning Dr. Battle will review basic concepts of linear functions and piecewise functions and how they can be used as models for real-world applications. She will also introduce techniques for using a spreadsheet to analyze data.

Transfer Functions in Artificial Neural Networks - A Simulation-Based Tutorial

Artificial neural networks are based on computational units that resemble basic information processing properties of biological neurons in an abstract and simplified manner. Generally, these formal neurons model an input-output behaviour as it is also often used to characterize biological neurons. The neuron is treated as a black box; spatial extension and temporal dynamics present in biological neurons are most often neglected. Even though artificial neurons are simplified, they can show a variety of input-output relations, depending on the transfer functions they apply. This unit on transfer functions provides an overview of different transfer functions and offers a simulation that visualizes the input-output behaviour of an artificial neuron depending on the specific combination of transfer functions.

Design and Impact of Awareness Functions – A Study about Social Media in Virtual Teams

The usage of social media in leisure time settings has become a prominent research topic. However, less research has been done on the design of social media in collaboration settings. In this study, we investigate how social media can support asynchronous collaboration in virtual teams and specifically how they can increase activity awareness. On the basis of an open source social networking platform, we present two prototype designs: a standard platform with basic support for information processing, communication and process – as suggested by Zigurs and Buckland (1998) – and an advanced platform with additional support for activity awareness via specialfeed functions. We argue that the standard platform already conveys activity awareness to a certain extent, however, that this awareness can be increased even more by the feeds in the advanced platform. Both prototypes are tested in a field experiment and evaluated with respect to their impact on perceived activity awareness, coordination and satisfaction. We show that the advanced design increases coordination and satisfaction through increased perceived activity awareness.

Targeting GRPR in urological cancers--from basic research to clinical application

Gastrin releasing peptide (GRP) is a regulatory peptide that acts through its receptor (GRPR) to regulate physiological functions in various organs. GRPR is overexpressed in neoplastic cells of most prostate cancers and some renal cell cancers and in the tumoral vessels of urinary tract cancers. Thus, targeting these tumours with specifically designed GRP analogues has potential clinical application. Potent and specific radioactive, cytotoxic or nonradioactive GRP analogues have been designed and tested in various animal tumour models with the aim of receptor targeting for tumour diagnosis or therapy. All three categories of compound were found suitable for tumour targeting in animal models. The cytotoxic and nonradioactive GRP analogues have not yet shown convincing tumour-reducing effects in human trials; however, the first clinical studies of radioactive GRP analogues--both agonists and antagonists--suggest promising opportunities for both diagnostic tumour imaging and radiotherapy of prostate and other GRPR-expressing cancers.

Improving executive functions in 5- and 6-year-olds: Evaluation of a small group intervention in prekindergarten and kindergarten children

Research suggests a central role of executive functions for children's cognitive and social development during preschool years, especially in promoting school readiness. Interventions aiming to improve executive functions are therefore being called for. The present study examined the effect of a small group intervention implemented in kindergarten settings focusing on basic components of executive functions, i.e., working memory, interference control and cognitive flexibility. A total of 135 children enrolled in Swiss prekindergarten (5-year-olds) and kindergarten (6-year-olds) were involved. Results revealed that the small group intervention promoted gains in all three included components of executive functions: prekindergarten children substantially improved their working memory and cognitive flexibility processes, whereas significant training effects were found for the kindergarten children in interference control. Implications of these findings for early intervention programs and for tailoring preschool curricula are discussed, particularly with respect to children's school readiness. Copyright © 2011 John Wiley & Sons, Ltd.

The Gut Microbiome and Cirrhosis: Basic Aspects

In this chapter the basic aspects helping to understand the microbiome in terms of quantity, diversity, complexity, function, and interaction with the host are discussed. First the nomenclature, definitions of taxa, and measures of diversity as well as methods to unravel this kingdom are outlined. A brief summary on its physiological relevance for general health and the functions exerted specifically by the microbiome is presented. Differences in the composition of the microbiome along the gastrointestinal tract and across the gut wall and its interindividual variations, enterotypes, and stability are highlighted. The reader will be familiarized with all different modulators impacting on the microbiome, namely, intrinsic and extrinsic factors. Intrinsic factors include gastrointestinal secretions (gastric acid, bile, pancreatic juice, mucus), antimicrobial peptides, motility, enteric nervous system, and host genotype. Extrinsic factors are mainly dietary choices, hygiene, stress, alcohol consumption, exercise, and medications. The second part of the chapter focuses on quantitative and qualitative changes in microbiome in liver cirrhosis. The mechanisms contributing to dysbiosis, small intestinal bacterial overgrowth, and bacterial translocation are delineated underscoring their role for the liver-gut axis.

COMMUNITY-FOCUSED FUNCTIONS IN PUBLIC HEALTH NURSING: A COMPARISON OF PERCEPTIONS

This descriptive cross-sectional survey compared the perceptions of public health nursing practitioners, educators and administrators along two dimensions: the importance of community-focused functions in public health nursing and which occupational categories in public health are responsible for those functions. More than 50 percent of the mailed questionnaires that were sent to a systematic stratified nationwide sample of public health nurses were returned. In general, respondents: were female, were in their 40s, received their basic nursing education in baccalaureate programs, had either a baccalaureate or a master's degree, worked in official agencies or schools, and had approximately 14 years of experience in public health with six in their present position.^ Significant differences between practitioners, educators and administrators were found in their perceptions of both the importance of community-focused functions in public health nursing and in which occupational category they indicated as having the major responsibility to perform those functions. Educators and administrators perceived community-focused functions as more important than did practitioners. Overall the occupational category of administrator was indicated as having the major responsibility for performing community-focused functions.^

DISTRIBUTION FUNCTIONS, MEAN SQUARED ERRORS, AND CONFIDENCE LIMITS FOR RIDGE REGRESSION ESTIMATORS

A large number of ridge regression estimators have been proposed and used with little knowledge of their true distributions. Because of this lack of knowledge, these estimators cannot be used to test hypotheses or to form confidence intervals.^ This paper presents a basic technique for deriving the exact distribution functions for a class of generalized ridge estimators. The technique is applied to five prominent generalized ridge estimators. Graphs of the resulting distribution functions are presented. The actual behavior of these estimators is found to be considerably different than the behavior which is generally assumed for ridge estimators.^ This paper also uses the derived distributions to examine the mean squared error properties of the estimators. A technique for developing confidence intervals based on the generalized ridge estimators is also presented. ^

Leader Rural Development Program in Spain: Profile and Functions of Workers in Local Action Groups.

Occupations in the labor market are linked with to a minimum basic training and other capacities. Hired workers should be able to accomplish required functions related to their specific job. Regarding the rural development labor market, local action groups? workers have defined performance areas?projects, strategy, organization and training & market?but specific functions within each of these areas are not as clearly defined. Neither both, basic training and capacities needed to perform each job profile within the local action group are defined. This communication analyses training and other capacities linked to each of the job profiles within the local action group. Functions within each of the performance areas previously defined are also analyzed regarding the job profiles.

Myelin basic protein kinase activity in tomato leaves is induced systemically by wounding and increases in response to systemin and oligosaccharide elicitors

In response to wounding, a 48-kDa myelin basic protein (MBP) kinase is activated within 2 min, both locally and systemically, in leaves of young tomato plants. The activating signal is able to pass through a steam girdle on the stem, indicating that it moves through the xylem and does not require intact phloem tissue. A 48-kDa MBP kinase is also activated by the 18-amino acid polypeptide systemin, a potent wound signal for the synthesis of systemic wound response proteins (swrps). The kinase activation by systemin is strongly inhibited by a systemin analog having a Thr-17 → Ala-17 substitution, which is a powerful antagonist of systemin activation of swrp genes. A 48-kDa MBP kinase activity also increases in response to polygalacturonic acid and chitosan but not in response to jasmonic acid or phytodienoic acid. In def1, a mutant tomato line having a defective octadecanoid pathway, the 48-kDa MBP kinase is activated by wounding and systemin as in the wild-type plants. This indicates that MBP kinase functions between the perception of primary signals and the DEF1 gene product. In response to wounding, the MBP kinase is phosphorylated on phosphotyrosine residues, indicating a relationship to the mitogen-activated protein kinase family of protein kinases.

Nuclear Activities of Basic Fibroblast Growth Factor: Potentiation of Low-Serum Growth Mediated by Natural or Chimeric Nuclear Localization Signals

Human basic fibroblast growth factor (FGF-2) occurs in four isoforms: a low molecular weight (LMW FGF-2, 18 kDa) and three high molecular weight (HMW FGF-2, 22, 22.5, and 24 kDa) forms. LMW FGF-2 is primarily cytoplasmic and functions in an autocrine manner, whereas HMW FGF-2s are nuclear and exert activities through an intracrine, perhaps nuclear, pathway. Selective overexpression of HMW FGF-2 forms in fibroblasts promotes growth in low serum, whereas overexpression of LMW FGF-2 does not. The HMW FGF-2 forms have two functional domains: an amino-terminal extension and a common 18-kDa amino acid sequence. To investigate the role of these regions in the intracrine signaling of HMW FGF-2, we produced stable transfectants of NIH 3T3 fibroblasts overexpressing either individual HMW FGF-2 forms or artificially nuclear-targeted LMW FGF-2. All of these forms of FGF-2 localize to the nucleus/nucleolus and induce growth in low serum. The nuclear forms of FGF-2 trigger a mitogenic stimulus under serum starvation conditions and do not specifically protect the cells from apoptosis. These data indicate the existence of a specific role for nuclear FGF-2 and suggest that LMW FGF-2 represents the biological messenger in both the autocrine/paracrine and intracrine FGF-2 pathways.

Purification and Characterization of a Galactose-Rich Basic Glycoprotein in Tobacco1

We found a galactose-rich basic glycoprotein (GBGP) in the cell walls of cultured tobacco (Nicotiana tabacum) cells. GBGP and extensin were isolated as the major components of basic, salt-extracted cell wall glycoproteins. GBGP and extensin were separated by gel filtration in 6 m guanidine hydrochloride as 49- and 90-kD peaks, respectively, and further purified with reverse-phase chromatography. The protein moiety of GBGP constitutes about one-half of the molecule (w/w) and contains lysine (16%), proline (12%), hydroxyproline (10%), tyrosine (4%), alanine (7%), leucine (6%), and cystine (1.4%). Galactose accounted for 72% of the sugar moiety, arabinose content was low (17%), and a significant amount of mannose (7%) was found. No immunological cross-reaction was detected between GBGP and extensin. The antibody against native GBGP with sugar chains reacted with other glycoproteins on the gel blots, whereas the antibodies against deglycosylated GBGP and native extensin were highly specific. Immunolocalization analysis in tobacco stems showed that GBGP is specific to parenchyma tissue and that extensin localizes in the epidermis. This tissue-specific and exclusive distribution suggests important functions of these basic glycoproteins.

Shared functions in vivo of a glycosyl-phosphatidylinositol-linked aspartyl protease, Mkc7, and the proprotein processing protease Kex2 in yeast.

The MKC7 gene was isolated as a multicopy suppressor of the cold-sensitive growth phenotype of a yeast kex2 mutant, which lacks the protease that cleaves pro-alpha-factor and other secretory proproteins at pairs of basic residues in a late Golgi compartment in yeast. MKC7 encodes an aspartyl protease most closely related to product of the YAP3 gene, a previously isolated multicopy suppressor of the pro-alpha-factor processing defect of a kex2 null. Multicopy MKC7 suppressed the alpha-specific mating defect of a kex2 null as well as multicopy YAP3 did, but multicopy YAP3 was a relatively weak suppressor of kex2 cold sensitivity. Overexpression of MKC7 resulted in production of a membrane-associated proteolytic activity that cleaved an internally quenched fluorogenic peptide substrate on the carboxyl side of a Lys-Arg site. Treatment with phosphatidylinositol-specific phospholipase C shifted Mkc7 activity from the detergent to the aqueous phase in a Triton X-114 phase separation, indicating that membrane attachment of Mkc7 is mediated by a glycosyl-phosphatidylinositol anchor. Although disruption of MKC7 or YAP3 alone resulted in no observable phenotype, mkc7 yap3 double disruptants exhibited impaired growth at 37 degrees C. Disruption of MKC7 and YAP3 in a kex2 null mutant resulted in profound temperature sensitivity and more generalized cold sensitivity. The synergism of mkc7, yap3, and kex2 null mutations argues that Mkc7 and Yap3 are authentic processing enzymes whose functions overlap those of Kex2 in vivo.

On the uniform approximation of Cauchy continuous functions

In the context of real-valued functions defined on metric spaces, it is known that the locally Lipschitz functions are uniformly dense in the continuous functions and that the Lipschitz in the small functions - the locally Lipschitz functions where both the local Lipschitz constant and the size of the neighborhood can be chosen independent of the point - are uniformly dense in the uniformly continuous functions. Between these two basic classes of continuous functions lies the class of Cauchy continuous functions, i.e., the functions that map Cauchy sequences in the domain to Cauchy sequences in the target space. Here, we exhibit an intermediate class of Cauchy continuous locally Lipschitz functions that is uniformly dense in the real-valued Cauchy continuous functions. In fact, our result is valid when our target space is an arbitrary Banach space.