CiteULike: Author Raab

Depletion of B cells in vivo by a chimeric mouse human monoclonal antibody to CD20.

ME Reff — 2008-07-19T17:59:44-00:00

Blood, Vol. 83, No. 2. (15 January 1994), pp. 435-445.

Murine monoclonal antibody 2B8 specifically recognizes the CD20 phosphoprotein expressed on the surface of normal B lymphocytes and B-cell lymphomas. The light- and heavy-chain variable regions of 2B8 were cloned, after amplification by the polymerase chain reaction, into a cDNA expression vector that contained human IgG1 heavy chain and human kappa-light chain constant regions. High-level expression of chimeric-2B8 antibody (C2B8) was obtained in Chinese hamster ovary cells. Purified C2B8 exhibited antigen binding affinity and human-tissue reactivity similar to the native murine antibody. In vitro studies showed the ability of C2B8 to bind human C1q, mediate complement-dependent cell lysis of human B-lymphoid cell lines, and lyse human target cells through antibody-dependent cellular cytotoxicity. Infusion of macaque cynomolgus monkeys with doses ranging from 1.6 mg/kg to 6.4 mg/kg resulted in greater than 98% depletion of peripheral blood (PB) B cells and 40% to 70% depletion of lymph node B cells. Recovery of PB B cells usually started at 2 weeks after treatment and required 60 to greater than 90 days to reach normal levels. As much as 95% depletion of B cells in peripheral lymph nodes and bone marrow was observed following weekly injections of 16.8 mg/kg antibody. No toxicity was observed in any of the animals. These results offer the possibility of using an "immunologically active" chimeric anti-CD20 antibody as an alternative approach in the treatment of B-cell lymphoma.

Joined-up government and privacy in the United Kingdom: managing tensions between data protection and social policy. Part II

Christine Bellamy — 2005-05-18T19:30:12-00:00

Public Administration, Vol. 83, No. 2. (June 2005), pp. 393-415.

Behavioural, physiological and immunological consequences of social status and aggression in chronically coexisting resident-intruder dyads of male rats

A Raab — 2008-05-14T13:06:11-00:00

Physiology & Behavior, Vol. 36, No. 2. (1986), pp. 223-228.

The behavioural and physiological consequences of social status and reciprocal fighting in resident-intruder dyads of Long Evans male rats were evaluated. Before a chronic cohabitation of 10 days, residents and intruders were individually housed for one month to increase their aggressiveness. Control animals included isolates, i.e., animals kept individually housed throughout the experiment and pair-housed rats, i.e., pairs of rats housed together from their rats in the laboratory. In 19 out of 20 dyads, a clear dominance relationship developed with an advantage to the resident in 68% of the cases. Dominants showed more exploratory activity than subordinates in an open-field test at the end of the cohabitation period; subordinates groomed longer than animals from other experimental groups. Dominants had lower pain thresholds than individually and pair-housed animals. Both dominants and subordinates had higher tyrosine hydroxylase enzymatic activities in the left adrenal than isolated and pair-housed rats. Subordinates lost body weight and had higher plasma corticosteroid concentrations than animals from the other experimental groups. In addition, they had smaller thymus glands and reduced spleen lymphocyte responses to mitogenic stimulation in vitro, in comparison to dominant animals. These results show that subordination in the dyadic resident-intruder paradigm leads to a complex syndrome of behavioural and physiological changes, some of which may be modulated by the intensity of aggressive interactions.

Power amplifiers and transmitters for RF and microwave

FH Raab — 2008-05-09T23:54:52-00:00

Microwave Theory and Techniques, IEEE Transactions on, Vol. 50, No. 3. (2002), pp. 814-826.

The generation of RF/microwave power is required not only in wireless communications, but also in applications such as jamming, imaging, RF heating, and miniature dc/dc converters. Each application has its own unique requirements for frequency, bandwidth, load, power, efficiency, linearity, and cost. RF power is generated by a wide variety of techniques, implementations, and active devices. Power amplifiers are incorporated into transmitters in a similarly wide variety of architectures, including linear, Kalm, envelope tracking, outphasing, and Doherty. Linearity can be improved through techniques such as feedback, feedforward, and predistortion

SHPS-1 is a scaffold for assembling distinct adhesion-regulated multi-protein complexes in macrophages.

JF Timms — 2008-04-14T20:44:07-00:00

Current biology : CB, Vol. 9, No. 16. (26 August 1999), pp. 927-930.

Inhibitory immunoreceptors downregulate signaling by recruiting Src homology 2 (SH2) domain-containing tyrosine and/or lipid phosphatases to activating receptor complexes [1]. There are indications that some inhibitory receptors might also perform other functions [2] [3]. In adherent macrophages, two inhibitory receptors, SHPS-1 and PIR-B, are the major proteins binding to the tyrosine phosphatase SHP-1. SHPS-1 also associates with two tyrosine-phosphorylated proteins (pp55 and pp130) and a protein tyrosine kinase [4]. Here, we have identified pp55 and pp130 as the adaptor molecules SKAP55hom/R (Src-kinase-associated protein of 55 kDa homologue) and FYB/SLAP-130 (Fyn-binding protein/SLP-76-associated protein of 130 kDa), respectively, and the tyrosine kinase activity as PYK2. Two distinct SHPS-1 complexes were formed, one containing SKAP55hom/R and FYB/SLAP-130, and the other containing PYK2. Recruitment of FYB/SLAP-130 to SHPS-1 required SKAP55hom/R, whereas PYK2 associated with SHPS-1 independently. Formation of both complexes was independent of SHP-1 and tyrosine phosphorylation of SHPS-1. Finally, tyrosine phosphorylation of members of the SHPS-1 complexes was regulated by integrin-mediated adhesion. Thus, SHPS-1 provides a scaffold for the assembly of multi-protein complexes that might both transmit adhesion-regulated signals and help terminate such signals through SHP-1-directed dephosphorylation. Other inhibitory immunoreceptors might have similar scaffold-like functions.

The Role of Fisheries-Induced Evolution

Howard Browman — 2008-04-12T13:45:19-00:00

Science, Vol. 320, No. 5872. (4 April 2008), pp. 47b-50.

10.1126/science.320.5872.47b

Antibody recognition imaging by force microscopy

Anneliese Raab — 2008-03-17T14:12:50-00:00

Nat Biotech, Vol. 17, No. 9. (1999), pp. 901-905.

Exploratory Network Visualization: Simultaneous Display of Actor Status and Connections

U Brandes — 2008-03-17T03:31:05-00:00

(2001)

We propose a novel visualization approach that facilitates graphical exploration and communication of relative actor status in social networks. The main idea is to map, in a drawing of the entire network, actor status scores to vertical coordinates. The resulting problem of determining horizontal positions of actors and routing of connecting lines such that the overall layout is readable is algorithmically di#- cult, yet well-studied in the literature on graph drawing. We outline a...

Yersinia pestis YopD 150-287 fragment is partially unfolded in the native state.

R Raab — 2008-03-11T14:49:20-00:00

Protein Expr Purif, Vol. 58, No. 1. (March 2008), pp. 53-60.

Yersinia pestis, a human and animal pathogen, uses the type III secretion system (T3SS) for delivering virulence factors and effectors into the host cells. The system is conserved in animal pathogens and is hypothesized to deliver the virulence factors directly from bacterial to mammalian cells through a pore composed of YopB and YopD translocation proteins. The YopB and YopD translocator proteins must be delivered first to form a functional pore in the mammalian cell. The criteria by which Yersinia selects the two proteins for initial delivery are not known and we hypothesized that the extensive binding by the chaperone and partial unfolding of the unbound region may be the criteria for selection. The YopB and YopD translocator proteins, unlike other effectors, have a common chaperone SycD, which binds through multiple regions. Due to the small size of the pore, we hypothesized that many of the transported virulence factors, translocators YopB and YopD included, are delivered in a partially unfolded state stabilized by binding to specific chaperones. The YopD protein binds the chaperone through amino acid (a.a.) 53-149 and a.a. 278-292 regions but biophysical characterization of YopD has not been possible due to the lack of an expression system for soluble, large fragments of the protein. In our present work, we demonstrated that the YopD 150-287 peptide fragment, almost the full soluble C-terminal part, including the non-interacting peptide fragment YopD 150-277, was partially unfolded in its native state by a combination of biophysical methods: circular dichroism, quasi-elastic light scattering, chemical unfolding and 8-anilino-1-naphthalene sulfonate (ANS) binding. The secondary structure of the peptide converted easily between alpha-helical and random coil states at neutral pH, and the alpha-helical state was almost fully recovered by lowering the temperature to 263 K. The current results suggest that YopD 150-287 peptide may have the postulated transport-competent state in its native form.

Adaptor SKAP-55 Binds p21 Activating Exchange Factor RasGRP1 and Negatively Regulates the p21-ERK Pathway in T-Cells.

H Schneider — 2008-03-11T11:41:04-00:00

PLoS ONE, Vol. 3, No. 3. (2008)

While the adaptor SKAP-55 mediates LFA-1 adhesion on T-cells, it is not known whether the adaptor regulates other aspects of signaling. SKAP-55 could potentially act as a node to coordinate the modulation of adhesion with downstream signaling. In this regard, the GTPase p21(ras) and the extracellular signal-regulated kinase (ERK) pathway play central roles in T-cell function. In this study, we report that SKAP-55 has opposing effects on adhesion and the activation of the p21(ras) -ERK pathway in T-cells. SKAP-55 deficient primary T-cells showed a defect in LFA-1 adhesion concurrent with the hyper-activation of the ERK pathway relative to wild-type cells. RNAi knock down (KD) of SKAP-55 in T-cell lines also showed an increase in p21(ras) activation, while over-expression of SKAP-55 inhibited activation of ERK and its transcriptional target ELK. Three observations implicated the p21(ras) activating exchange factor RasGRP1 in the process. Firstly, SKAP-55 bound to RasGRP1 via its C-terminus, while secondly, the loss of binding abrogated SKAP-55 inhibition of ERK and ELK activation. Thirdly, SKAP-55-/- primary T-cells showed an increased presence of RasGRP1 in the trans-Golgi network (TGN) following TCR activation, the site where p21(ras) becomes activated. Our findings indicate that SKAP-55 has a dual role in regulating p21(ras)-ERK pathway via RasGRP1, as a possible mechanism to restrict activation during T-cell adhesion.

Usability and Feasibility of PmEB: A Mobile Phone Application for Monitoring Real Time Caloric Balance

Christopher Tsai — 2008-02-24T00:36:50-00:00

Pervasive Health Conference and Workshops, 2006 (2006), pp. 1-10.

Obesity is a major public health challenge with over 65% of U.S. adults either overweight or obese. Estimated annual costs of obesity are around $78.5 billion. Self-monitoring is a critical skill for successful weight management. However, self-monitoring is labor-intensive and compliance is often difficult. In this paper, we describe the Patient-Centered Assessment and Counseling Mobile Energy Balance (PmEB) cell phone application that allows users to self-monitor caloric balance in real time. We developed and applied a four-phase iterative research and development methodology. We conducted a usability study and a preliminary feasibility study. The one month feasibility study measured compliance and satisfaction among a sample of 15 participants randomized to one of three groups: 1) a paper diary group, 2) a PmEB group with one daily prompt, and 3) a PmEB group with three daily prompts. PmEB scored highly on usability, compliance, and satisfaction. In addition, cell phone group users scored PmEB the same as or better than Paper Group members scored the paper diary in nearly all categories. Thematic analysis of comments revealed very positive reviews of PmEB as well as areas for improvement. PmEB is both usable and feasible for self-monitoring in weight management, and our iterative pilot study methodology was effective in improving its usability

Synapse-1: A High-Speed General Purpose Parallel Neurocomputer System

U Ramacher — 2008-02-16T23:00:02-00:00

pp. 774-781.

This paper describes the general purpose neurocomputer SYNAPSE--1 which has been developed in cooperation between Siemens Munich and the University of Mannheim. This system contains one of the most powerful processors available for neural algorithms, the neuro signal processor MA16. The prototype system executes a test algorithm 8,000 times as fast as a Sparc--2 workstation. This processing speed has been achieved by using a system architecture which is optimally adapted to the general...

A programmable platform for software-defined radio

HM Bluethgen — 2008-02-08T15:51:37-00:00

System-on-Chip, 2003. Proceedings. International Symposium on (2003), 15.

Integrated circuits for communication systems are usually designed with the primary goal of minimizing silicon area and power consumption. Usually, this yields a solution where each functional block in the algorithm is mapped directly into a dedicated hardware block. The hardware blocks provide limited flexibility by setting of parameters but only as far as it has been specified during the design phase. According to the abovementioned reasons we believe that more flexibility is necessary that requires fully programmable solutions based on digital signal processors (DSP). For the development of an SDR platform architecture our primary design goal is to find the most flexible and easy-to-program solution within a specified power budget for the baseband processing.

Light Traps Using Spontaneous Forces

DE Pritchard — 2008-02-05T03:04:33-00:00

Physical Review Letters, Vol. 57, No. 3. (21 July 1986), 310.

We show that the optical Earnshaw theorem does not always apply to atoms and that it is possible to confine atoms by spontaneous light forces produced by static laser beams. A necessary condition for such traps is that the atomic transition rate cannot depend only on the light intensity. We give several general approaches by which this condition can be met and present a number of specific trap designs illustrating these approaches. These traps have depths on the order of a kelvin and volumes of several cubic centimeters.

Dark Networks as Problems

Jorg Raab — 2008-01-23T14:24:13-00:00

J Public Adm Res Theory, Vol. 13, No. 4. (1 October 2003), pp. 413-439.

Networks and networking are viewed as ways of dealing with complex problems that beset both the state and society. Homelessness, health care, and crime are all viewed as problems that networks can manage better than single organizations can. This article views these problems as networks that must be confronted if Western democracies wish to deal with terrorism, drug smuggling, and the manifold pathologies that confront failed states. In this article we adopt the perspective of networks as problems. The majority of the literature on networks and collaboration is quite positive. Collaborative networks are seen as appropriate devices to tackle public management problems and successfully coordinate political, social, and economic action. From the level of global governance, European integration, sectoral policy networks at the national level, and service implementation networks at the local level, these devices are all viewed as ways of solving governance problems in a complex and differentiated world. The research proposed here intends to develop a more holistic view of this phenomenon by looking at dark networks. The article tries to evaluate how network structures and governance are used for criminal or immoral ends. Because the judgment of ends is inherently normative, we propose to talk about overt and legal versus covert and illegal networks. We then analyze where the similarities and differences between the two sets are and what we might be able to learn regarding both forms if we mirror them against each other. The article develops a set of propositions drawn from selected cases of drug-trafficking networks, the diamond and weapons trade, and the Al Qaeda terrorist network. 10.1093/jopart/mug029

Cournot Competition between Teams: An Experimental Study

Philippe Raab — 2008-01-09T14:18:51-00:00

In the economic literature on market competition, firms are often modeled as single decision makers and the internal organization of the firm is neglected (unitary player assumption). However, as the literature on strategic delegation suggests, one can not generally expect that teams behave equivalently to individuals in Cournot competition. Nevertheless, there are models of team-organization such that teams and individuals are behaviorally equivalent in Cournot oligopoly providing a...

Preoperative versus postoperative chemoradiotherapy for rectal cancer.

R Sauer — 2007-10-01T21:06:08-00:00

N Engl J Med, Vol. 351, No. 17. (21 October 2004), pp. 1731-1740.

BACKGROUND: Postoperative chemoradiotherapy is the recommended standard therapy for patients with locally advanced rectal cancer. In recent years, encouraging results with preoperative radiotherapy have been reported. We compared preoperative chemoradiotherapy with postoperative chemoradiotherapy for locally advanced rectal cancer. METHODS: We randomly assigned patients with clinical stage T3 or T4 or node-positive disease to receive either preoperative or postoperative chemoradiotherapy. The preoperative treatment consisted of 5040 cGy delivered in fractions of 180 cGy per day, five days per week, and fluorouracil, given in a 120-hour continuous intravenous infusion at a dose of 1000 mg per square meter of body-surface area per day during the first and fifth weeks of radiotherapy. Surgery was performed six weeks after the completion of chemoradiotherapy. One month after surgery, four five-day cycles of fluorouracil (500 mg per square meter per day) were given. Chemoradiotherapy was identical in the postoperative-treatment group, except for the delivery of a boost of 540 cGy. The primary end point was overall survival. RESULTS: Four hundred twenty-one patients were randomly assigned to receive preoperative chemoradiotherapy and 402 patients to receive postoperative chemoradiotherapy. The overall five-year survival rates were 76 percent and 74 percent, respectively (P=0.80). The five-year cumulative incidence of local relapse was 6 percent for patients assigned to preoperative chemoradiotherapy and 13 percent in the postoperative-treatment group (P=0.006). Grade 3 or 4 acute toxic effects occurred in 27 percent of the patients in the preoperative-treatment group, as compared with 40 percent of the patients in the postoperative-treatment group (P=0.001); the corresponding rates of long-term toxic effects were 14 percent and 24 percent, respectively (P=0.01). CONCLUSIONS: Preoperative chemoradiotherapy, as compared with postoperative chemoradiotherapy, improved local control and was associated with reduced toxicity but did not improve overall survival.

<I>Myo</I>-Inositol: a marker of reactive astrogliosis in glial tumors?

Elke Hattingen — 2007-08-21T12:04:33-00:00

NMR in Biomedicine, Vol. 9999, No. 9999. (2007), n/a.

In a prospective study, two-dimensional 1H-MRS with TE of 30 ms was performed before surgery in 56 patients with glial brain tumors. Concentrations of myo-inositol (MI), trimethylamine (TMA) and creatine/phosphocreatine (tCr) were evaluated for the whole tumor and scaled to the normal-appearing contralateral brain tissue. To assign changes in MI to specific tissue pathology, the normalized peak and mean concentrations of MI were correlated with TMA and tCr concentrations. TMA is accepted as a marker of proliferating tumor tissue, and tCr might be a marker of reactive astrogliosis. The mean and peak concentrations of MI and tCr correlated positively (r = 0.7), but not the concentrations of MI and TMA. The absolute concentration of MI was significantly increased in all tumor tissues (5.55 ± 2.92 mM; mean ± SD) compared with the normal-appearing white matter (4.33 ± 1.22 mM, p = 0.005), with the highest concentrations for gliomatoses (n = 10) and grade II oligoastrocytomas (n = 3). Significant differences (P = 0.004) between low- and high-grade astrocytomas were found for TMA (1.67 ± 0.32 mM and 2.65 ± 0.86 mM, respectively), but not for MI (5.92 ± 1.98 mM and 5.49 ± 3.27 mM, respectively). As increased MI and tCr concentrations were found in gliomatosis and other cerebral diseases associated with marked astrogliosis, this process may also be responsible for the observed changes in MI in other glial tumors. Copyright © 2007 John Wiley & Sons, Ltd.

Independent CD28 signaling via VAV and SLP-76: a model for in trans costimulation.

CE Rudd — 2007-07-07T23:42:42-00:00

Immunol Rev, Vol. 192 (April 2003), pp. 32-41.

The two-signal theory of T-cell activation dictates that optimal T-cell responses are determined by a least two signals, the primary signal provided by the antigen-receptor complex (TCR/CD3) and the second signal provided by a costimulatory receptor. Recent studies have underlined the importance of in trans costimulation via CD28 in the regulation of transplant rejection. Previous studies have emphasized the ability of CD28 to operate in cis in the amplification of signaling through the T-cell receptor (TCR). Our recent work has demonstrated that CD28 can activate the lipid kinase phosphatidylinositol 3-kinase (PI-3K) and can cooperate with adapters Vav and SLP-76 to influence the induction of interleukin (IL)-2 and IL-4 transcription in the absence of TCR ligation. CD28-PI-3K binding and CD28-VAV/SLP-76 cooperativity provide a pathway to account for in trans costimulation in T-cell immunity.

Exploratory Network Visualization: Simultaneous Display of Actor Status and Connections

U Brandes — 2007-05-09T08:22:54-00:00

A system for quantifying dynamic protein interactions defines a role for Herceptin in modulating ErbB2 interactions

TS Wehrman — 2006-12-18T14:10:27-00:00

PNAS, Vol. 103, No. 50. (12 December 2006), pp. 19063-19068.

The orphan receptor tyrosine kinase ErbB2 is activated by each of the EGFR family members upon ligand binding. However, difficulties monitoring the dynamic interactions of the membrane receptors have hindered the elucidation of the mechanism of ErbB2 activation. We have engineered a system to monitor protein-protein interactions in intact mammalian cells such that different sets of protein interactions can be quantitatively compared. Application of this system to the interactions of the EGFR family showed that ErbB2 interacts stably with the EGFR and ErbB3, but fails to spontaneously homooligomerize. The widely used anti-cancer antibody Herceptin was found to effectively inhibit the interaction of the EGFR and ErbB2 but not to interfere with the interaction of ErbB2-ErbB3. Treatment of cells expressing EGFR and ErbB2 with Herceptin results in increased EGFR homooligomerization in the presence of EGF and a subsequent rapid internalization and down-regulation of the EGFR. In summary, the protein interaction system described here enabled the characterization of ErbB2 interactions within the biological context of the plasma membrane and provides insight into the mechanism of Herceptin action on cells overexpressing ErbB2. 10.1073/pnas.0605218103

Poly(Ethylene Glycol): An Ideal Spacer for Molecular Recognition Force Microscopy/Spectroscopy.

Peter Hinterdorfer — 2007-03-28T15:30:19-00:00

Single Molecules, Vol. 1, No. 2. (2000), pp. 99-103.

In this review, we report recent molecular recognition studies of our group. The surface chemistry by which ligands are covalently coupled to force microscopy tips is described. Poly(ethylene glycol), which is used as spacer for the ligands, was shown to be a most suitable crosslinker for force spectroscopy and microscopy experiments. Basic principles of force spectroscopy are discussed and the successful application of this technique to several biological systems is demonstrated. Information about kinetic rates, affinities, and the dynamic structure of the binding pocket are obtained. Furthermore, it is shown that combining molecular recognition with dynamic force microscopy leads to recognition imaging and renders localization of binding sites with nm accuracy possible. These techniques show State Physics, University of Linz great potential for investigating the molecular dynamics of ligand-receptor binding and the epitope mapping of recptors during biological processes.

Transcriptomal comparison of human dermal lymphatic endothelial cells ex vivo and in vitro.

N Wick — 2007-01-22T10:12:37-00:00

Physiol Genomics, Vol. 28, No. 2. (17 January 2007), pp. 179-192.

The in vivo functions of lymphatic endothelial cells depend on their microenvironment, which cannot be fully reproduced in vitro. Because of technical limitations, gene expression in uncultured, "ex vivo" lymphatic endothelial cells has not been characterized at the molecular level. We combined tissue micropreparation and direct cell isolation with DNA chip experiments to identify 159 genes differentiating human lymphatic endothelial cells from blood vascular endothelial cells ex vivo. The same analysis performed with cultured primary cells revealed that only 19 genes characteristic for lymphatic endothelium ex vivo retained this property upon culture, while 27 marker genes were newly induced. In addition, a set of panendothelial genes could be recognized. The propagation of lymphatic endothelial cells in culture stimulated transcription of genes associated with cell turnover, basic metabolism, and the cytoskeleton. On the other hand, there was downregulation of genes encoding extracellular matrix components, signaling via transmembrane tyrosine kinase pathways and the chemokine (C-C) ligand 21. Direct ex vivo analysis of the lymphatic endothelial cell transcriptome is helpful for the understanding of the physiology of the lymphatic vascular system and of the pathogenesis of its diseases.

An approach to nonstandard quantum mechanics

Andreas Raab — 2007-01-16T13:25:41-00:00

(27 Dec 2006)

We use nonstandard analysis to formulate quantum mechanics in hyperfinite-dimensional spaces. Self-adjoint operators on hyperfinite-dimensional spaces have complete eigensets, and bound states and continuum states of a Hamiltonian can thus be treated on an equal footing. We show that the formalism extends the standard formulation of quantum mechanics. To this end we develop the Loeb-function calculus in nonstandard hulls. The idea is to perform calculations in a hyperfinite-dimensional space, but to interpret expectation values in the corresponding nonstandard hull. We further apply the framework to non-relativistic quantum scattering theory. For time-dependent scattering theory, we identify the starting time and the finishing time of a scattering experiment, and we obtain a natural separation of time scales on which the preparation process, the interaction process, and the detection process take place. For time-independent scattering theory, we derive rigorously explicit formulas for the Moller wave operators and the S-Matrix.

Toward a Systems Approach to Understanding Plant Cell Walls

Chris Somerville — 2007-01-15T12:25:42-00:00

Science, Vol. 306, No. 5705. (24 December 2004), pp. 2206-2211.

One of the defining features of plants is a body plan based on the physical properties of cell walls. Structural analyses of the polysaccharide components, combined with high-resolution imaging, have provided the basis for much of the current understanding of cell walls. The application of genetic methods has begun to provide new insights into how walls are made, how they are controlled, and how they function. However, progress in integrating biophysical, developmental, and genetic information into a useful model will require a system-based approach. 10.1126/science.1102765

FYB (FYN binding protein) serves as a binding partner for lymphoid protein and FYN kinase substrate SKAP55 and a SKAP55-related protein in T cells

Junke Liu — 2006-11-09T14:47:04-00:00

PNAS, Vol. 95, No. 15. (21 July 1998), pp. 8779-8784.

10.1073/pnas.95.15.8779

Classic Works In RF Engineering: Combiners, Couplers, Transformers, and Magnetic Materials (Artech House Microwave Library)

Frederick Raab — 2006-08-14T12:59:40-00:00

(31 January 2006)

The growing interest in commercial RF applications and high-frequency engineering has triggered a scramble for fundamental design and analysis information, which until now has been largely scattered in the literature and often hard to find. This expertly compiled resource gives microwave engineers instant one-stop access to a vast range of essential source material in a single convenient volume. Over 100 classic papers provide definitive treatment of design, analysis, and applications of ferrite/powdered iron circuits, RF transformers, power splitters, power combiners and directional couplers, all organized for ready reference. Engineers quickly find proven techniques, design solutions, and core data for the full range of HF components — from toroidal-wound inductors, multielement transmission lines, and broadband balun transformers, to hybrid power dividers and directional channel-separation filters. <P>What's more, this one-of-a-kind encyclopedic guide features current, context-providing introductions and commentary that help engineers evaluate the various possible solutions to design challenges they face, plus informative reviews of next-generation technology. Certain to become a reference "Bible", this volume brings together a wealth of fundamental information critical to the work of all professionals in the field.

Surveillance and the human-machine interface

David Mason — 2005-05-10T14:34:58-00:00

Information, Communication and Society, Vol. 8, No. 1. (March 2005), pp. 81-83.

ADAP-SLP-76 Binding Differentially Regulates Supramolecular Activation Cluster (SMAC) Formation Relative to T Cell-APC Conjugation

Hongyan Wang — 2006-06-13T12:58:25-00:00

J. Exp. Med., Vol. 200, No. 8. (18 October 2004), pp. 1063-1074.

T cell-APC conjugation as mediated by leukocyte function-associated antigen-1 (LFA-1)-intercellular adhesion molecule (ICAM)-1 binding is followed by formation of the supramolecular activation cluster (SMAC) at the immunological synapse. The intracellular processes that regulate SMAC formation and its influence on T cell function are important questions to be addressed. Here, using a mutational approach, we demonstrate that binding of adaptor adhesion and degranulation promoting adaptor protein (ADAP) to SLP-76 differentially regulates peripheral SMAC (pSMAC) formation relative to conjugation. Although mutation of the YDDV sites (termed M12) disrupted SLP-76 SH2 domain binding and prevented the ability of ADAP to increase conjugation and LFA-1 clustering, M12 acted selectively as a dominant negative (DN) inhibitor of pSMAC formation, an effect that was paralleled by a DN effect on interleukin-2 production. ADAP also colocalized with LFA-1 at the immunological synapse. Our findings identify ADAP-SLP-76 binding as a signaling event that differentially regulates SMAC formation, and support a role for SMAC formation in T cell cytokine production. 10.1084/jem.20040780

Improving the 'how' and 'what' decisions of elite table tennis players

Markus Raab — 2006-04-11T12:05:14-00:00

Human Movement Science, Vol. 24, No. 3. (June 2005), pp. 326-344.

Training methods in sport usually focus on improving either technical or tactical aspects of performance, ignoring the fact that successful performance requires the athlete to simultaneously decide what movement to perform and how it should be executed. Young elite table tennis players were trained, in a first phase, to improve their forehand and backhand movements and, in a second phase, to make a tactical switch between forehand and backhand movements. Half of the players took part in behavioral training focusing on how to perform the required movements, whereas half received additional video feedback about their technical and tactical performance (decision training). The results indicate that improvements of how decisions (techniques) and what decisions (tactics) can occur as a consequence of combining technical and tactical training. These results were stable in delayed Post-test analyses of competitive matches. It was concluded that a combination of both technical and tactical training is beneficial to elite table tennis performers, particularly during early seasonal training programs.

The T-cell antigen CD5 acts as a receptor and substrate for the protein-tyrosine kinase p56lck.

M Raab — 2006-03-24T09:09:53-00:00

Mol Cell Biol, Vol. 14, No. 5. (May 1994), pp. 2862-2870.

CD5 is a T-cell-specific antigen which binds to the B-cell antigen CD72 and acts as a coreceptor in the stimulation of T-cell growth. CD5 associates with the T-cell receptor zeta chain (TcR zeta)/CD3 complex and is rapidly phosphosphorylated on tyrosine residues as a result of TcR zeta/CD3 ligation. However, despite this, the mechanism by which CD5 generates intracellular signals is unclear. In this study, we demonstrate that CD5 is coupled to the protein-tyrosine kinase p56lck and can act as a substrate for p56lck. Coexpression of CD5 with p56lck in the baculovirus expression system resulted in the phosphorylation of CD5 on tyrosine residues. Further, anti-CD5 and anti-p56lck coprecipitated each other in a variety of detergents, including Nonidet P-40 and Triton X-100. Anti-CD5 also precipitated the kinase from various T cells irrespective of the expression of TcR zeta/CD3 or CD4. No binding between p59fyn(T) and CD5 was detected in T cells. The binding of p56lck to CD5 induced a 10- to 15-fold increase in p56lck catalytic activity, as measured by in vitro kinase analysis. In vivo labelling with 32P(i) also showed a four- to fivefold increase in Y-394 occupancy in p56lck when associated with CD5. The use of glutathione S-transferase-Lck fusion proteins in precipitation analysis showed that the SH2 domain of p56lck could recognize CD5 as expressed in the baculovirus expression system. CD5 interaction with p56lck represents a novel variant of a receptor-kinase complex in which receptor can also serve as substrate. The CD5-p56lck interaction is likely to play roles in T-cell signalling and T-B collaboration.

CD28 signaling via VAV/SLP-76 adaptors: regulation of cytokine transcription independent of TCR ligation.

M Raab — 2005-10-04T13:41:43-00:00

Immunity, Vol. 15, No. 6. (December 2001), pp. 921-933.

Since CD28 provides cosignals in T cell responses, a key question is whether the coreceptor operates exclusively via TCRzeta/CD3 or also operates as an independent signaling unit. In this study, we show that CD28 can cooperate with VAV/SLP-76 adaptors to upregulate interleukin 2/4 transcription independently of TCR ligation. CD28 signaling is dependent on VAV/SLP-76 complex formation and induces membrane localization of these complexes. CD28-VAV/SLP-76 also functions in nonlymphoid cells to promote nuclear entry of NFAT, indicating that these adaptors are the only lymphoid components needed for this pathway. Further downstream, CD28-VAV/SLP-76 synergizes with Rac1 and causes F-actin remodelling proximal to receptor. Autonomous CD28 signaling may account for the distinct nature of the second signal and in trans amplification of T cell responses.

Soil Amino Acid Utilization among Species of the Cyperaceae: Plant and Soil Processes

Theodore Raab — 2005-05-06T17:31:05-00:00

Ecology, Vol. 80, No. 7. (1999), pp. 2408-2419.

An empirical model of amino acid transformations in an alpine soil

D Lipson — 2005-05-06T17:17:56-00:00

Soil Biology and Biochemistry, Vol. 33, No. 2. (February 2001), pp. 189-198.

Amino acids are potentially important nitrogen (N) sources for plants in many ecosystems. However, a quantitative understanding of organic N availability is lacking for most ecosystems. This study estimates seasonal amino acid fluxes in an alpine tundra soil using three independent data sets. In previous work in an alpine dry meadow ecosystem in the Front Range of the Colorado Rocky Mountains, we measured significant rates of amino acid production from soil peptides during the plant growing season. This suggested that proteolysis of native soil peptides could serve as a measure of amino acid availability to plants. Here we use a simple seasonal model to test the hypothesis that soil amino acid concentrations can be predicted from rates of soil proteolysis and amino acid degradation by microbes. We present seasonal data for turnover rates of the amino acid, glutamate, in soil, and experiments on the effects of temperature and moisture on amino acid fluxes in soil. We relate these studies to previously published values of proteolysis and soil amino acid concentrations in this alpine soil. Our model shows that independent measurements of proteolytic rates, microbial amino acid uptake, and soil amino acid concentrations are consistent with each other, and that most changes in the soil amino acid pool can be explained by protease and microbial uptake rates, after adjusting for environmental conditions. Immediately after snow melts in the spring and again in late summer after the onset of monsoonal rains, measured soil amino acid concentrations were slightly lower than model predictions from measured protease and microbial uptake rates. This could indicate that, at certain times, an additional sink for amino acids exists, such as rapid plant uptake or loss from the ecosystem due to leaching. We estimate amino acid production during the snow-free season at our study site to be 103 g amino acid-N m-2 growing season-1. This value is not only consistent with the three data sets used in this study, but also with previous studies of N transformations in the Colorado alpine. This flux could provide Kobresia myosuroides, the dominant plant in this ecosystem, with 50-100% of its annual N requirement, based on previous plant-microbe competition experiments.

Proctocolectomy and pelvic pouch--is a diverting stoma dangerous for the patient?

U Gunnarsson — 2005-04-18T19:09:54-00:00

Colorectal Dis, Vol. 6, No. 1. (January 2004), pp. 23-27.

OBJECTIVE: A diverting loop ileostomy was previously considered mandatory for minimizing the effects of septic complications in pelvic pouch surgery. During the past decade there has been a trend towards omission of the loop ileostomy without obvious signs of increased numbers of pouch complications or impaired long-term function. The aim of the present study was to evaluate the risk of complications associated with the construction and closure of the loop ileostomy itself. PATIENTS AND METHODS: Complications following diverting loop ileostomies in 143 patients subjected to restorative pelvic pouch surgery during the period 1983-97 were studied retrospectively by evaluation of case records. RESULTS: In the period between discharge after pelvic pouch surgery and closure of the loop ileostomy, 20 (14%) patients were hospitalized because of excessive stoma flow and 19 (13%) patients were treated for other surgical complications, of whom 10 (7%) required surgical intervention. In the early postoperative period (within 30 days) after closure of the loop ileostomy, 18 (13%) patients suffered complications necessitating surgery. Another 12 (8%) patients were hospitalized because of intestinal obstruction that could be treated conservatively. CONCLUSION: The proportion of complications associated with diverting loop ileostomies in pelvic pouch surgery was considerable. A randomised controlled multicentre study is ethically defensible and is recommended.