CT-2576, an inhibitor of phospholipid signaling, suppresses constitutive and induced expression of human immunodeficiency virus.

Viruses such as human immunodeficiency virus (HIV) require cellular activation for expression. Cellular activation in lymphoid cells is associated with augmented accumulation of certain phosphatidic acid (PA) species derived from the hydrolysis of glycan phosphatidylinositol (GPI). This suggests that activation of a phospholipid pathway may play a role in initiation of viral replication. To test this hypothesis, we examined the effect of tat gene expression on the production of cellular PA species, as the Tat protein is essential for HIV expression and has been implicated in activating the expression of multiple host cellular genes. Expression of tat increased the expression of PA. We then tested whether synthetic inhibitors of PA metabolism would inhibit activation of the HIV long terminal repeat by Tat and tumor necrosis factor alpha (TNF-alpha). CT-2576 suppressed both PA generation induced by Tat and HIV long terminal repeat-directed gene expression in response to Tat or TNF-alpha at a posttranscriptional step. CT-2576 also inhibited constitutive as well as TNF-alpha- and interleukin 6-induced expression of HIV p24 antigen in chronically infected U1 cells and in peripheral blood lymphocytes acutely infected with a clinical isolate of HIV. Pharmacological inhibition of synthesis of selected PA species may therefore provide a therapeutic approach to suppression of HIV replication.

Human TAFII31 protein is a transcriptional coactivator of the p53 protein.

The p53 protein activates transcription of a target gene by binding to a specific DNA response element and interacting with the transcriptional apparatus of RNA polymerase II. The amino-terminal domain of p53 interacts with a component of the TFIID basal transcription complex. The human TATA-binding-protein-associated factor TAFII31, a component of TFIID, has been identified as a critical protein required for p53-mediated transcriptional activation. TAFII31 and p53 proteins bind to each other via amino acid residues in the amino-terminal domain of p53 that are essential for transcription. Antibodies directed against TAFII31 protein inhibit p53-activated but not basal transcription in vitro. These results demonstrate that TAFII31 is a coactivator for the p53 protein.

Coexpression of two functionally independent p58 inhibitory receptors in human natural killer cell clones results in the inability to kill all normal allogeneic target cells.

In the present study, we define a group of natural killer (NK) clones (group 0) that fails to lyse all of the normal allogeneic target cells analyzed. Their specificity for HLA class I molecules was suggested by their ability to lyse class I-negative target cells and by the fact that they could lyse resistant target cells in the presence of selected anti-class I monoclonal antibodies. The use of appropriate target cells represented by either HLA-homozygous cell lines or cell transfectants revealed that these clones recognized all the HLA-C alleles. By the use of monoclonal antibodies directed to either GL183 or EB6 molecules, we showed that the EB6 molecules were responsible for the recognition of Cw4 and related alleles, while the GL183 molecules recognized Cw3 (and related C alleles). These data suggest that the GL183 and the EB6 molecules can function, in individual NK clones, as independent receptors for two different groups of HLA-C alleles, (which include all known alleles for locus C), thus resulting in their inability to lyse all normal HLA-C+ target cells. Indirect immunofluorescence and fluorescence-activated cell sorting analysis revealed that the presently defined GL183+EB6+ group 0 NK clones brightly express EB6 molecules (EB6bright) while the GL183+EB6+ group 2 clones (unable to recognize Cw4) express an EB6dull phenotype. These data also imply that the density of EB6 receptors may be critical for the generation of an optimal negative signal upon interaction with appropriate HLA-C alleles.

Efficient in vivo antitumor effect of an immunotoxin based on ribotoxin α-sarcin in nude mice bearing human colorectal cancer xenografts

Tagging of RNases, such as the ribotoxin α-sarcin, with the variable domains of antibodies directed to surface antigens that are selectively expressed on tumor cells endows cellular specificity to their cytotoxic action. A recombinant single-chain immunotoxin based on the ribotoxin α-sarcin (IMTXA33αS), produced in the generally regarded as safe (GRAS) yeast Pichia pastoris, has been recently described as a promising candidate for the treatment of colorectal cancer cells expressing the glycoprotein A33 (GPA33) antigen, due to its high specific and effective cytotoxic effect on in vitro assays against targeted cells. Here we report the in vivo antitumor effectiveness of this immunotoxin on nude mice bearing GPA33-positive human colon cancer xenografts. Two sets of independent assays were performed, including three experimental groups: control (PBS) and treatment with two different doses of immunotoxin (50 or 100 μg/ injection) (n = 8). Intraperitoneal administration of IMTXA33αS resulted in significant dose-dependent tumor growth inhibition. In addition, the remaining tumors excised from immunotoxin-treated mice showed absence of the GPA33 antigen and a clear inhibition of angiogenesis and proliferative capacity. No signs of immunotoxin-induced pathological changes were observed from specimens tissues.Overall these results show efficient and selective cytotoxic action on tumor xenografts, combined with the lack of severe side effects, suggesting that IMTXA33αS is a potential therapeutic agent against colorectal cancer.

RGBD Human-Hand recognition for the Interaction with Robot-Hand

New low cost sensors and the new open free libraries for 3D image processing are permitting to achieve important advances for robot vision applications such as tridimensional object recognition, semantic mapping, navigation and localization of robots, human detection and/or gesture recognition for human-machine interaction. In this paper, a method to recognize the human hand and to track the fingers is proposed. This new method is based on point clouds from range images, RGBD. It does not require visual marks, camera calibration, environment knowledge and complex expensive acquisition systems. Furthermore, this method has been implemented to create a human interface in order to move a robot hand. The human hand is recognized and the movement of the fingers is analyzed. Afterwards, it is imitated from a Barret hand, using communication events programmed from ROS.

Brief Communication : Cranial Nonmetric Trait Database on the Internet

This brief note announces the publication of a nonmetric cranial trait database as a freely available resource on the Internet at: http://library.queensu.ca/web- doc/ssdc/cntd. The files were constructed in the program Excel, and are available also in comma-delimited format. These one-observer data on 38 traits were recorded in 1963–2003 in skeletal collections curated at many muse- ums. The 8,016 crania represent individuals from a broad geographic and temporal range of recent human popula- tions, with regions best represented being the Arctic and northwestern North America. Am J Phys Anthropol 152:551–553, 2013.

First steps toward harmonized human biomonitoring in Europe : demonstration project to perform human biomonitoring on a European scale

'Reproduced with permission from Environmental Health Perspectives'

The Determinants of Investment in Information and Communication Technologies. Bruges European Economic Research (BEER) Papers 16/March 2010

In this paper we investigate the determinants of ICT investment at the macro level for a panel of ten countries over the period 1992-2005. We argue that, since ICT is a General Purpose Technology, its diffusion can be understood only considering the interaction with institutional and structural factors. The empirical results are in line with this view: facilitating factors such as changes in regulation, human capital and the sectoral composition of the economy are relevant determinants for increasing ICT investment.

1982 human rights report : March 1983.

Mode of access: Internet.

Guidelines for meeting the communication needs of individuals with hearing loss.

"P.O. 3186"--Colophon.

Performance audit : Funding provided by state agencies to Heartland Human Services /

"House Resolution Number 1307 directed the Office of the Auditor General to conduct a performance audit of the State moneys provided by or through State agencies to Heartland Human Services (Heartland). Heartland is a non-profit corporation in Effingham, Illinois that provides outpatient services and 24-hour residential services to adults with mental illness."

Influence apart from Adoption: How Interaction between Programming and Scientific Practices Shapes Modes of Inquiry in Four Oceanography Teams

Thesis (Ph.D.)--University of Washington, 2016-06

A Way of Doing Things: Exploring and Applying the Alexander Technique for Choral Conductors

Thesis (D.M.A.)--University of Washington, 2016-06

What the family brings: Gathering evidence for strengths-based work

Families attending child and adolescent mental health (CAMH) services are often assumed to have problems in key areas such as communication, belonging/acceptance and problem-solving. Family therapy is often directed towards addressing these difficulties. With increasing emphasis in family therapy and human services fields over the last decade on identifying and building from strengths, a different starting point has been advocated. This paper describes a large survey of the self-reported pre-therapy functioning of children and families using a public CAMH service (n = 416). Before commencing family therapy parents identified family strengths across a range of key areas, despite the burden of caring for children with moderate to severe mental health problems. This evidence supports theoretical and clinical work that advocates a strengths perspective, and highlights how resilience framed in family (and social) rather than individual terms enables a greater appreciation of how strengths may be harnessed in therapeutic work.

Trust me, I'm your boss: Trust and power in supervisor-supervisee communication

This study examined employees' perceptions of trust, power and mentoring in manager-employee relationships in a variety of sectors, including health care, education, hospitality and retail. The main theoretical frameworks used were communication accommodation theory and social identity theory, in examining the manager-employee relationships from an in-group/out-group perspective. Computer-aided content analyses revealed a number of emergent communication and relationship themes that impact upon the level of 'in-groupness' and therefore trust in supervisor-supervisee relationships. While it may be illusory to believe that any organization can enjoy complete trust among its workforce, it is clear that certain communication characteristics can result in greater trust in manager-employee relationships, even within the context of organizational constraints. It is argued that the results of the study could be used to inform human resource management academics of key aspects of managerial communication that should be further researched, and also provide insights into the main communication skills that managers should focus upon to improve trust in the workplace.