An Effective Algorithm for the Futile Questioning Problem

In the futile questioning problem, one must decide whether acquisition of additional information can possibly lead to the proof of a conclusion. Solution of that problem demands evaluation of a quantified Boolean formula at the second level of the polynomial hierarchy. The same evaluation problem, called Q-ALL SAT, arises in many other applications. In this paper, we introduce a special subclass of Q-ALL SAT that is at the first level of the polynomial hierarchy. We develop a solution algorithm for the general case that uses a backtracking search and a new form of learning of clauses. Results are reported for two sets of instances involving a robot route problem and a game problem. For these instances, the algorithm is substantially faster than state-of-the-art solvers for quantified Boolean formulas.     

A Novel Long-Chained Acetate in the Defensive Secretion of Thrips

Defensive secretions of adult and larval Suocerathrips linguis (Phlaeothripidae, Thysanoptera) were found to contain a long-chained acetate, (11Z)-11,19-eicosadienyl acetate, that was not previously known to occur naturally. This substance occurred together with octadecyl acetate and other long-chained acetates. The eicosadienyl acetate repels ants and spreads on the surface of such potential predators. The mixture can provide a long-lasting surface coating.     

Increasing Workplace Independence for People with Cognitive Disabilities by Leveraging Distributed Cognition among Caregivers and Clients

This paper describes a group configuration that is currently employed to support the everyday living and working activities of people with cognitive disabilities. A client receiving face-to-face, often one-to-one, assistance from a dedicated human job coach is characteristic of this traditional configuration. We compare it with other group configurations that are used in cooperative and distributed work practices and propose an alternative configuration titled active distributed support system. In so doing, we highlight requirements that are unique to task support for people with cognitive disabilities. In particular, we assert that the knowledge of how to perform such activities is shared not only among people, but also between people and artifacts. There is a great potential for innovative uses of ubiquitous and mobile technologies to support these activities. A survey of technologies that have been developed to provide these individuals with greater levels of independence is then presented. These endeavors often attempt to replace human job coaches with computational cognitive aids. We discuss some limitations of such approaches and present a model and prototype that extends the computational job coach by incorporating human caregivers in a distributed one-to-many support system.     

Limitations of electrospray ionization of fulvic and humic acids as visible from size exclusion chromatography with organic carbon and mass spectrometric detection

A method was developed to link size exclusion chromatography electrospray ionization mass spectrometry (SEC-ESI-MS) analyses of fulvic and humic acids with SEC and organic carbon detection (SEC-OCD), the latter providing an absolute measure of the amount of organic matter eluting from the SEC column. This approach allows us to determine which molecular weight fraction of the complex polydisperse mixtures is detectable by ESI-MS. It could be shown that the cone voltage setting for the ESI interface has strong impact on ESI-MS detection. Using conventional settings for low molecular weight compounds, the high molecular weight (HMW) compounds are hardly amenable to ESI-MS. With increasing cone voltage, an increasing signal intensity is obtained for the HMW fraction that elutes at shorter retention times. However, mostly fragment ions are obtained under these conditions. Thus, the range of compounds amenable to ESI-MS analysis is restricted by the limited stability of the fulvic and humic acid molecules of higher molecular weight in the electrospray process rather than by the mass spectrometer used. Compounds above 1000 amu are hardly visible as intact ions. However, insight into structural characteristics of these compounds can be gained by investigating their fragment ions by SEC-ESI-MS. The use of SEC-OCD parallel to SEC-MS helps to assess and optimize the detection potential of ESI-MS for polydisperse mixtures.     

Prenatal Stress and Risk for Psychopathology: Specific Effects or Induction of General Susceptibility?

This review focuses on prenatal stress as a risk factor for psychopathology. Evidence from animal studies is summarized, and the relevance of prenatal stress models in animals for human studies is discussed. In the offspring of prenatally stressed animals, overactivity and impaired negative feedback regulation of the hypothalamic-pituitary-adrenal axis are consistent findings and may reflect a pathophysiological mechanism involved in the development of psychopathology. Reduced activity of the opioid GABA/benzodiazepine, serotonin, and dopamine systems and increased activity of the sympathico-adrenal system have been found as well. These alterations have been linked to a diverse spectrum of psychopathology. Therefore, the evidence supports the view that exposure to prenatal stress may result in a general susceptibility to psychopathology, rather than exerting a direct effect on a specific form of psychopathology. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Prediction of Response to Cisplatin-Based Neoadjuvant Chemotherapy of Muscle-Invasive Bladder Cancer Patients by Molecular Subtyping including KRT and FGFR Target Gene Assessment

Patients with muscle-invasive urothelial carcinoma achieving pathological complete response (pCR) upon neoadjuvant chemotherapy (NAC) have improved prognosis. Molecular subtypes of bladder cancer differ markedly regarding sensitivity to cisplatin-based chemotherapy and harbor FGFR treatment targets to various content. The objective of the present study was to evaluate whether preoperative assessment of molecular subtype as well as FGFR target gene expression is predictive for therapeutic outcome—rate of ypT0 status—to justify subsequent prospective validation within the “BladderBRIDGister”. Formalin-fixed paraffin-embedded (FFPE) tissue specimens from transurethral bladder tumor resections (TUR) prior to neoadjuvant chemotherapy and corresponding radical cystectomy samples after chemotherapy of 36 patients were retrospectively collected. RNA from FFPE tissues were extracted by commercial kits, Relative gene expression of subtyping markers (e.g., KRT5, KRT20) and target genes (FGFR1, FGFR3) was analyzed by standardized RT-qPCR systems (STRATIFYER Molecular Pathology GmbH, Cologne). Spearman correlation, Kruskal–Wallis, Mann–Whitney and sensitivity/specificity tests were performed by JMP 9.0.0 (SAS software). The neoadjuvant cohort consisted of 36 patients (median age: 69, male 83% vs. female 17%) with 92% of patients being node-negative during radical cystectomy after 1 to 4 cycles of NAC. When comparing pretreatment with post-treatment samples, the median expression of KRT20 dropped most significantly from DCT 37.38 to 30.65, which compares with a 128-fold decrease. The reduction in gene expression was modest for other luminal marker genes (GATA3 6.8-fold, ERBB2 6.3-fold). In contrast, FGFR1 mRNA expression increased from 33.28 to 35.88 (~6.8-fold increase). Spearman correlation revealed positive association of pretreatment KRT20 mRNA levels with achieving pCR (r = 0.3072: p = 0.0684), whereas pretreatment FGFR1 mRNA was associated with resistance to chemotherapy (r = −0.6418: p < 0.0001). Hierarchical clustering identified luminal tumors of high KRT20 mRNA expression being associated with high pCR rate (10/16; 63%), while the double-negative subgroup with high FGFR1 expression did not respond with pCR (0/9; 0%). Molecular subtyping distinguishes patients with high probability of response from tumors as resistant to neoadjuvant chemotherapy. Targeting FGFR1 in less-differentiated bladder cancer subgroups may sensitize tumors for adopted treatments or subsequent chemotherapy.     

Combining Radiation- with Immunotherapy in Prostate Cancer: Influence of Radiation on T Cells

Radiation of tumor cells can lead to the selection and outgrowth of tumor escape variants. As radioresistant tumor cells are still sensitive to retargeting of T cells, it appears promising to combine radio- with immunotherapy keeping in mind that the radiation of tumors favors the local conditions for immunotherapy. However, radiation of solid tumors will not only hit the tumor cells but also the infiltrated immune cells. Therefore, we wanted to learn how radiation influences the functionality of T cells with respect to retargeting to tumor cells via a conventional bispecific T cell engager (BiTE) and our previously described modular BiTE format UNImAb. T cells were irradiated between 2 and 50 Gy. Low dose radiation of T cells up to about 20 Gy caused an increased release of the cytokines IL-2, TNF and interferon-γ and an improved capability to kill target cells. Although radiation with 50 Gy strongly reduced the function of the T cells, it did not completely abrogate the functionality of the T cells.     

Inhibition of Human Urokinase-Type Plasminogen Activator (uPA) Enzyme Activity and Receptor Binding by DNA Aptamers as Potential Therapeutics through Binding to the Different Forms of uPA

Urokinase-type plasminogen activator is widely discussed as a marker for cancer prognosis and diagnosis and as a target for cancer therapies. Together with its receptor, uPA plays an important role in tumorigenesis, tumor progression and metastasis. In the present study, systematic evolution of ligands by exponential enrichment (SELEX) was used to select single-stranded DNA aptamers targeting different forms of human uPA. Selected aptamers allowed the distinction between HMW-uPA and LMW-uPA, and therefore, presumably, have different binding regions. Here, uPAapt-02-FR showed highly affine binding with a K_D of 0.7 nM for HMW-uPA and 21 nM for LMW-uPA and was also able to bind to pro-uPA with a K_D of 14 nM. Furthermore, no cross-reactivity to mouse uPA or tissue-type plasminogen activator (tPA) was measured, demonstrating high specificity. Suppression of the catalytic activity of uPA and inhibition of uPAR-binding could be demonstrated through binding with different aptamers and several of their truncated variants. Since RNA aptamers are already known to inhibit uPA-uPAR binding and other pathological functions of the uPA system, these aptamers represent a novel, promising tool not only for detection of uPA but also for interfering with the pathological functions of the uPA system by additionally inhibiting uPA activity.     

Bewertung von Altlasten im Grundwasser anhand der Meiofaunagemeinschaften—erste Ergebnisse.

Kurzfassung Im Rahmen eines Pilotprogramms wurden in Rheinland-Pfalz fünf Standorte mit Altlasten unterschiedlicher Herkunft auf das Auftreten und die Verteilung von Grundwassermeiofauna untersucht. Ziel dieser Vorstudie war es, erste Daten zur Verteilung der Grundwassermeiofauna in Altlaststandorten zu sammeln. Die Ergebnisse eines Standortes, hier bezeichnet als militärische Altlastfläche C, werden im Detail vorgestellt. Trotz des vorläufigen Charakters der Ergebnisse konnten für einzelne Organismengruppen deutliche Verteilungsmuster gefunden werden. Während die Crustacea (Krebstiere) mit LCKW (leichtflüchtige chlorierte Kohlenwasserstoffe) belastete Bereiche mieden, traten v. a. Nematoda und Oligochaeta flächendeckend und teilweise in hohen Abundanzen in allen untersuchten Bereichen auf. Diese beobachteten Verteilungen scheinen nicht nur arten- oder taxaabhängig zu sein, sondern möglicherweise auch abhängig von der Art des Schadstoffs. Langfristig ist anzustreben, die Grundwassermeiofauna auf ihre Eignung als Bioindikator zu testen. Bisher praktizierten physikochemischen Analysemethoden soll damit ein kostengünstiges, faunistisch begründetes Monitoringsystem beigestellt werden, wie es sich in Oberflächengewässern seit Jahrzehnten bewährt hat.

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Assessment of contaminated groundwater sites using meiofaunal assemblage patterns—first results.

Abstract In Rhineland-Palatinate, Germany, a pilot program has been carried out to investigate the groundwater meiofauna at five contaminated sites. Aim of the study was to obtain first field data on the distribution of meiofauna at sites with varying contamination. Site C, a former militarily area, is introduced in more detail. In spite of the preliminary character of our data set, the fauna exhibited clear distribution patterns in relation to contamination. Crustaceans were found to colonize areas with low or non-existent concentrations of volatile halogenated hydrocarbons (VOC), whereas nematodes and oligochaetes occurred on site scale in more or less high abundances. The sensitivity to pollution observed seems not only to depend on species or taxa, but probably also on the type of contamination. For the future it is planned to test the suitability of groundwater meiofauna to serve as bioindicators as routinely practised for surface water systems for many decades. Complementary to hydrochemical methods, a faunistical biomonitoring on groundwater fauna can be an economical and effictive tool.