A directly spliced exon 10-containing CD44 variant promotes the metastasis and homotypic aggregation of aggressive non-Hodgkin's lymphoma

Variants of the CD44 cell-surface adhesion molecule include additional sequences encoded by combinations of exons from the membrane proximal domain (exons 6-14). Preliminary studies suggest that these additional variable membrane proximal sequences may alter the ligand specificity, glycosylation, and biologic function of CD44. In earlier studies, we found that primary extranodal and widely disseminated aggressive non-Hodgkin's lymphomas (NHLs) and normal activated B cells expressed a directly spliced exon 10-containing variant (CD44ex10), whereas normal resting B cells expressed larger exon 10-containing variants (CD44ex10-14 and CD44ex7-14). To obtain additional information regarding the function of exon 10-containing CD44 variants in aggressive NHL, we generated aggressive NHL transfectants that expressed CD44ex10, CD44ex10-14, CD44ex7-14, the standard CD44 isoform (CD44H), or vector alone, and evaluated the local tumorogenicity, aggregation, and metastatic potential of these transfectants. CD44ex10 aggressive NHL transfectants were more likely to cause local tumor formation in nude mice than transfectants expressing the larger exon 10-containing variants, CD44H, or vector alone. In addition, cell suspensions derived from CD44ex10 local tumors exhibited far greater homotypic aggregation than those obtained from other CD44 or vector-only local tumors. In nude mice that received CD44ex10 transfectants, distant metastases were also significantly more likely to develop than in animals that were given either the CD44ex10-14, CD44ex7-14, CD44H, or vector-only transfectants. These data provide the first evidence that the directly spliced exon 10-containing CD44 variant (CD44ex10) has a unique biologic function in aggressive NHL.     

Target complicity in the confirmation and disconfirmation of erroneous perceiver expectations: immediate and longer-term implications

The authors explored the role of target self-presentational goals in the expectation confirmation process within the context of simulated employment interviews. As predicted, applicants encouraged to be deferential inadvertently succumbed to their interviewers' expectation; applicants encouraged to be challenging, to advance their own agenda, did not. The challenging-motivated applicants succeeded in disconfirming negative expectations by presenting favorable information about themselves even in the face of negatively constraining interviewer questions; other theoretically relevant behaviors were not supported as mediators. Of added interest, the self-fulfilling prophecies observed for the deference-motivated applicants carried over to a 2nd interview because of changes in applicant self-perceptions following the 1st interview.     

Final report of a phase II evaluation of paclitaxel in patients with advanced squamous cell carcinoma of the head and neck: an Eastern Cooperative Oncology Group trial (PA390)

BACKGROUND: A number of single agents have been tested in patients with carcinoma of the head and neck receiving palliative treatment. In general, 15-30% of patients achieve a partial response lasting 3-4 months. Treatment has not been shown to alter survival rates. It is clear that new drugs with potentially greater activity need to be identified. For this purpose, the Eastern Cooperative Oncology Group conducted a Phase II evaluation of paclitaxel. METHODS: Patients with recurrent, metastatic, or locally advanced, incurable squamous cell carcinoma of the head and neck were eligible. The dose and schedule tested was the maximum tolerable dose of 250 mg/m2 determined from Phase I trials using a 24-hour infusion schedule and granulocyte-colony stimulating factor support. Courses were given at 3-week intervals until progression of disease was documented. Dose modifications were specified for hematologic toxicity and for neurotoxicity. RESULTS: Thirty-four patients were registered on study and 30 were eligible. Severe or life-threatening granulocytopenia was the most frequent toxicity observed, occurring in 91% of patients. Prior to response evaluation, one patient died of sepsis and one died of a myocardial infarct. Response was observed in 40% of eligible patients (4 complete and 8 partial responses). The median duration of response was 4.5 months (range, 2-20 months), with a median survival of 9.2 months and a 1-year survival rate of 33%. CONCLUSIONS: These results indicate that paclitaxel is an active agent for the treatment of squamous cell carcinoma of the head and neck. Studies evaluating alternative infusion schedules and combination regimens currently are underway.     

On Chaos and Neural Networks: The Backpropagation Paradigm

In training feed-forward neural networks using the backpropagation algorithm, a sensitivity to the values of the parameters of the algorithm hasbeen observed. In particular, it has been observed that this sensitivity with respect to the values of the parameters, such as thelearning rate, plays an important role in the final outcome. In thistutorial paper, we will look at neural networks from a dynamical systemspoint of view andexamine its properties. To this purpose, we collect results regarding chaostheory as well as the backpropagation algorithmand establish a relationship between them. We study in detail as an example the learning of the exclusive OR,an elementary Boolean function. The following conclusions hold for our XOR neural network: no chaos appears for learning rates lower than 5, when chaosoccurs, it disappears as learning progresses. For non-chaotic learning rates, the network learns faster than for other learning rates for which chaos occurs.     

What do people desire in others? A sociofunctional perspective on the importance of different valued characteristics.

Humans, as discriminately social creatures, make frequent judgments about others' suitability for interdependent social relations. Which characteristics of others guide these judgments and, thus, shape patterns of human affiliation? Extant research is only minimally useful for answering this question. On the basis of a sociofunctional analysis of human sociality, the authors hypothesized that people highly value trustworthiness and (to a lesser extent) cooperativeness in others with whom they may be interdependent, regardless of the specific tasks, goals, or functions of the group or relationship, but value other favorable characteristics (e.g., intelligence) differentially across such tasks, goals, or functions. Participants in 3 studies considered various characteristics for ideal members of interdependent groups (e.g., work teams, athletic teams) and relationships (e.g., family members, employees). Across different measures of trait importance and different groups and relationships, trustworthiness was considered extremely important for all interdependent others; the evidence for the enhanced importance of cooperativeness across different interdependence contexts was more equivocal. In contrast, people valued other characteristics primarily as they were relevant to the specific nature of the interdependent group or relationship. These empirical investigations illuminate the essence of human sociality with its foundation of trust and highlight the usefulness of a theoretically derived framework of valued characteristics. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Personal need for structure: Individual differences in the desire for simpler structure.

Individual differences in the desire for simple structure may influence how people understand, experience, and interact with their worlds. Studies 1 and 2 revealed that the Personal Need for Structure (PNS) scale (M. Thompson, M. Naccarato, and K. Parker, 1989) possesses sufficient reliability and convergent and discriminant validity. In Studies 3–5, Ss high in PNS were especially likely to organize social and nonsocial information in less complex ways, stereotype others, and complete their research requirements on time. These data suggest that people differ in their chronic desire for simple structure and that this difference can have important social–cognitive and behavioral implications. A consideration of chronic information-processing motives may facilitate the theoretical integration of social cognition, affect, motivation, and personality. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Perceiver self-presentational goals as moderators of expectancy influences: Ingratiation and the disconfirmation of negative expectancies.

Self-fulfilling prophecy processes enable people to confirm their negative expectancies for others. The perceiver goal of ingratiation was hypothesized to alter this behavioral dynamic and thus lead perceivers to disconfirm their negative expectancies. In an interview setting, interviewer Ss' expectancies and interaction goals were manipulated. As anticipated, "no goal" interviewers were relatively cold and challenging toward their negative-expectancy applicants; as a result, these applicants performed somewhat less favorably, consistent with interviewer expectancies. In contrast, "liking goal" interviewers were relatively warm and unthreatening toward their negative-expectancy applicants; as a result, these applicants performed favorably, disconfirming interviewer expectancies. These data support a framework in which perceiver self-presentation goals are conceptualized to moderate the expectancy-confirmation process. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Inhibition of calcineurin phosphatase activity in adult bone marrow transplant patients treated with cyclosporine A

In vitro studies have demonstrated that cyclosporine A (CsA) acts by inhibiting the phosphatase activity of calcineurin, an important mediator of T-cell activation. The relationship of CsA administration in vivo, calcineurin activity, and graft-versus-host disease (GVHD) has yet to be studied. The calcineurin activities of mononuclear cells isolated from 62 bone marrow transplant recipients and 12 normal volunteers were determined and analyzed with respect to administration of CsA, presence or absence of CsA in plasma, and presence or absence of GVHD. Of 62 patients, 33 were taking CsA and 29 were not. Early posttransplant (< 100 days), the calcineurin activity of patients on CsA was significantly lower than that of patients not on CsA (P = .0004) and than that of normal volunteers (P < .0001). Similarly, late posttransplant (> 100 days), the calcineurin activity of patients taking CsA was inhibited compared with normal volunteers (P < .05). The calcineurin activity of patients with acute GVHD who were taking CsA was lower than that of patients on CsA without acute GVHD matched for time posttransplant (P = .02). Calcineurin activity in patients on CsA with chronic GVHD was similar to those without chronic GVHD on drug. In conclusion, calcineurin activity is significantly suppressed by in vivo administration of CsA. The lower calcineurin activity of patients on CsA with acute GVHD suggests that CsA-resistant GVHD is not the result of inadequate suppression of calcineurin activity. These data suggest that if inhibition of calcineurin is the only physiologic target of CsA administration, simply increasing doses of CsA or treatment with other inhibitors of calcineurin, such as FK506, would not be expected to ameliorate GVHD.     

Mutation of the RET proto-oncogene is correlated with RET immunostaining in subpopulations of cells in sporadic medullary thyroid carcinoma

Mutations in the RET proto-oncogene, which encodes a receptor tyrosine kinase, are associated with the pathogenesis of medullary thyroid carcinoma (MTC). Somatic mutations in RET, predominantly at codon 918, and very rarely at codon 883, have been found in a proportion of sporadic MTC. We have previously shown that approximately 80% of sporadic MTCs had at least one subpopulation with a somatic RET mutation. Uneven distribution of somatic mutation within a single tumor or among metastases from a single individual was notable. In the present study, we sought to correlate RET expression, as demonstrated by RET immunohistochemistry, with mutation status in sporadic MTC for each tumor. Seventy evaluable subpopulations, belonging to 28 unrelated sporadic cases, comprising primary MTC and metastases, were immunostained with two different polyclonal antibodies raised against the C-terminus of RET. The regional presence of codon 918 or 883 seemed to coincide with increased RET immunopositivity in at least 62 of 70 (89%, P < 0.000001) tumor subpopulations. The reasons for this concordance are not entirely clear but could be related to either RNA or protein stability. Preliminary studies have suggested that the presence of somatic codon 918 mutation in MTC has a prognostic significance. If these preliminary results prove true, then given our data, we can further explore the feasibility of RET immunocytochemistry as a rapid assessment for the presence of somatic codon 918 for molecular diagnostic and prognostic purposes.     

CO2 Methanation in Microstructured Reactors – Catalyst Development and Process Design

The sulfur tolerance of mono‐ and bimetallic ruthenium catalysts for CO₂ hydrogenation was investigated in microchannel reactors. H₂S was selected as a model compound. It was found that a Ru/CeO₂ catalyst deactivates rapidly. Ni was a much better additive to improve the catalyst stability compared to Rh and serves as a sulfur trap. The influence of the support was evaluated showing that a SiO₂‐supported catalyst has a higher stability and better selectivity compared to CeO₂ and TiO₂. A plant concept was developed comprising two‐step methanation with a first adiabatic reactor stage followed by a plate heat‐exchanger reactor with integrated cooling which allows more than 97 % CO₂ conversion. A pilot plant will be put into operation in connection with a biogas plant and an electrolyser of 50 kW power consumption.