Response of high-risk of recurrence/progression bladder tumours expressing sialyl-Tn and sialyl-6-T to BCG immunotherapy

High risk of recurrence/progression bladder tumours is treated with Bacillus Calmette-Guérin (BCG) immunotherapy after complete resection of the tumour. Approximately 75% of these tumours express the uncommon carbohydrate antigen sialyl-Tn (Tn), a surrogate biomarker of tumour aggressiveness. Such changes in the glycosylation of cell-surface proteins influence tumour microenvironment and immune responses that may modulate treatment outcome and the course of disease. The aim of this work is to determine the efficiency of BCG immunotherapy against tumours expressing sTn and sTn-related antigen sialyl-6-T (s6T). METHODS: In a retrospective design, 94 tumours from patients treated with BCG were screened for sTn and s6T expression. In vitro studies were conducted to determine the interaction of BCG with high-grade bladder cancer cell line overexpressing sTn. RESULTS: From the 94 cases evaluated, 36 had recurrence after BCG treatment (38.3%). Treatment outcome was influenced by age over 65 years (HR=2.668; (1.344-5.254); P=0.005), maintenance schedule (HR=0.480; (0.246-0.936); P=0.031) and multifocality (HR=2.065; (1.033-4.126); P=0.040). sTn or s6T expression was associated with BCG response (P=0.024; P<0.0001) and with increased recurrence-free survival (P=0.001). Multivariate analyses showed that sTn and/or s6T were independent predictive markers of recurrence after BCG immunotherapy (HR=0.296; (0.148-0.594); P=0.001). In vitro studies demonstrated higher adhesion and internalisation of the bacillus to cells expressing sTn, promoting cell death. CONCLUSION: s6T is described for the first time in bladder tumours. Our data strongly suggest that BCG immunotherapy is efficient against sTn- and s6T-positive tumours. Furthermore, sTn and s6T expression are independent predictive markers of BCG treatment response and may be useful in the identification of patients who could benefit more from this immunotherapy

Hybrid SAT-Based Consistency Checking Algorithms for Simple Temporal Networks with Decisions

A Simple Temporal Network (STN) consists of time points modeling temporal events and constraints modeling the minimal and maximal temporal distance between them. A Simple Temporal Network with Decisions (STND) extends an STN by adding decision time points to model temporal plans with decisions. A decision time point is a special kind of time point that once executed allows for deciding a truth value for an associated Boolean proposition. Furthermore, STNDs label time points and constraints by conjunctions of literals saying for which scenarios (i.e., complete truth value assignments to the propositions) they are relevant. Thus, an STND models a family of STNs each obtained as a projection of the initial STND onto a scenario. An STND is consistent if there exists a consistent scenario (i.e., a scenario such that the corresponding STN projection is consistent). Recently, a hybrid SAT-based consistency checking algorithm (HSCC) was proposed to check the consistency of an STND. Unfortunately, that approach lacks experimental evaluation and does not allow for the synthesis of all consistent scenarios. In this paper, we propose an incremental HSCC algorithm for STNDs that (i) is faster than the previous one and (ii) allows for the synthesis of all consistent scenarios and related early execution schedules (offline temporal planning). Then, we carry out an experimental evaluation with KAPPA, a tool that we developed for STNDs. Finally, we prove that STNDs and disjunctive temporal networks (DTNs) are equivalent

New findings and a new species of the genus Ammothea (Pycnogonida, Ammotheidae), with an updated identification key to all Antarctic and sub-Antarctic species

Specimens of the pycnogonid genus Ammothea collected during the Polarstern cruise XXIII/8 (23 November 2006–30 January 2007) were studied. Nine species were recognized in this collection: Ammothea bentartica, A. bicorniculata, A. carolinensis, A. clausi, A. longispina, A. minor, A. spinosa, A. striata and A. tibialis. Three of them (A. bentartica, A. bicorniculata and A. tibialis) are reported for the second time, enlarging their known geographical and bathymetric range. In the present contribution, the observed morphological variability of all collected Ammothea species is described and discussed. For the identification and description of the material, different museum specimens were consulted. Among them, we have consulted part of the Discovery collection housed at the Natural History Museum in London. That material was initially identified by Isabella Gordon, a reputed author in the field of pycnogonid taxonomy. A new species, based on a museum specimen previously highly confused in the literature, is proposed in the present contribution as Ammothea isabellae n. sp. The new taxon is compared with its closest congeners, especially with A. longispina and A. stylirostris. Finally, we propose an updated dichotomous key to species covering all currently known Antarctic and sub-Antarctic Ammothea specie

Twist angle effects on the dynamic response of in-plane-switching liquid crystal displays

Twist angle effect on the response time of in-plane-switching liquid crystal displays are analyzed. We propose a device configuration whose top and bottom boundary liquid crystal layers are symmetric to each other with respect to the electric field direction. The analytical results of this device configuration indicate that the response time is improved at least 4X faster than that of a conventional in-plane-switching twisted-nematic mode and normal in-plane-switching mode.Comment: 12 Pages, 3 Figures. will be appeared in Appl. Phys. Let

Optogenetics and deep brain stimulation neurotechnologies

Brain neural network is composed of densely packed, intricately wired neurons whose activity patterns ultimately give rise to every behavior, thought, or emotion that we experience. Over the past decade, a novel neurotechnique, optogenetics that combines light and genetic methods to control or monitor neural activity patterns, has proven to be revolutionary in understanding the functional role of specific neural circuits. We here briefly describe recent advance in optogenetics and compare optogenetics with deep brain stimulation technology that holds the promise for treating many neurological and psychiatric disorders