Crohn's disease and ulcerative colitis mucosal T cells are stimulated by intestinal epithelial cells: implications for immunosuppressive therapy

BACKGROUND: Crohn's disease (CD) and ulcerative colitis (UC) are chronic inflammatory diseases, and their pathogenesis is attributed, in part, to alterations of the mucosal immune system. This study was designed to define the possible contribution of epithelial cells to the activation of lamina propria T lymphocytes (LPTs) in CD and UC. METHODS: LPTs isolated from CD, UC, and control surgical specimens were cocultured with freshly isolated allogeneic or autologous epithelial cells or epithelial cell lines. Resulting T-cell proliferation was evaluated by tritiated thymidine incorporation on day 5. RESULTS: When intestinal epithelial cells were used to stimulate mucosal T-cell proliferation, CD and UC LPTs were less responsive than control LPTs (p < 0.05 and p < 0.03, respectively). This difference between inflamed and control T cells was consistently observed by using a variety of different intestinal epithelial cell types. CONCLUSIONS: CD and UC mucosal T cells are hyporesponsive to activation by intestinal epithelial cells when compared with control LPTs. Elucidating the mechanism underlying the differential activation of CD and UC LPTs may help to better understand the immunopathogenesis of these conditions.     

Program load adaptive voltage generator for flash memories

This paper describes a program load voltage generator for flash memories. It is based on an adaptive feedback loop which senses the current delivered to the memory cells during programming and adjusts the output voltage accordingly to compensate for the voltage drop caused by the programming current across the bit-line select transistors. The proposed circuit (silicon area=0.065 mm²) was integrated in a 0.8-μm CMOS 4 Mb flash memory device (0.6 μm in the matrix). Experimental evaluations showed that very effective compensation is achieved, with bit-line voltage kept at the desired value during the whole programming operation. A spread as small as 70 mV was measured between the single-bit and 16-b programming cases     

Synthesis and antitumor evaluation of 2,5-disubstituted-indazolo[4, 3-gh]isoquinolin-6(2H)-ones (9-aza-anthrapyrazoles)

The synthesis and antitumor evaluation of 2, 5-disubstituted-indazolo[4,3-gh]isoquinolin-6(2H)-ones (9-aza-APs) are described. The key intermediates in the synthesis are benz[g]isoquinoline-5,10-diones which are substituted at positions 6 and 9 with groups of different nucleofugacity for SNAr displacements. The initial displacement of fluoride by a substituted hydrazine leads to the pyrazole analogues. Substitution of the remaining leaving group by an amine or BOC-protected amines leads to the 9-aza-APs 12. These analogues were converted into their maleate or hydrochloride salts 13. In two cases, namely, 13x and 13z, sidearm buildup was also employed in the synthetic pathway. In vitro evaluation of 9-aza-APs against the human colon tumor cell line LoVo uncovered for most of the compounds a cytotoxic potency lower than that of DuP-941 or mitoxantrone and comparable to that of doxorubicin. Only analogues 13c, 13n, and 13ff were as cytotoxic as DuP-941. Interestingly, while DuP-941 was highly cross-resistant in the LoVo cell line resistant to doxorubicin (LoVo/Dx), the 9-aza-APs carrying a distal lipophilic tertiary amine moiety in both chains were capable of overcoming the MDR resistance induced in this cell line. The 9-aza-APs show outstanding in vivo antitumor activity against both systemic P388 murine leukemia and MX-1 human mammary carcinoma transplanted in nude mice. At their optimal dosages, congeners 13a-c, 13f, 13n, 13q, 13x, and 13dd were highly effective against P388 leukemia with T/C% of 200-381, while the T/C% value of DuP-941 was 147. In the MX-1 tumor model, 24 compounds elicited percentages of tumor weight inhibitions (TWI) ranging from 50% to 99%. Congeners 13d, 13k, 13l, 13x, 13z, and 13ee emerged as the most effective ones, with TWI% 96, simliar to that of DuP-941 (TWI% = 95). On the basis of their efficacy profile in additional experimental tumors and lack of cardiotoxicity in preclinical models, two congeners have surfaced as potential clinical candidates.     

Portfolio approaches for constraint optimization problems

Within the Constraint Satisfaction Problems (CSP) context, a methodology that has proven to be particularly performant consists of using a portfolio of different constraint solvers. Nevertheless, comparatively few studies and investigations have been done in the world of Constraint Optimization Problems (COP). In this work, we provide a generalization to COP as well as an empirical evaluation of different state of the art existing CSP portfolio approaches properly adapted to deal with COP. The results obtained by measuring several evaluation metrics confirm the effectiveness of portfolios even in the optimization field, and could give rise to some interesting future research.     

Interactive teaching of task-oriented robot grasps

This paper focuses on the problem of grasp stability and grasp quality analysis. An elegant way to evaluate the stability of a grasp is to model its wrench space. However, classical grasp quality measures suffer from several disadvantages, the main drawback being that they are not task related. Indeed, constructive approaches for approximating the wrench space including also task information have been rarely considered. This work presents an effective method for task-oriented grasp quality evaluation based on a novel grasp quality measure. We address the general case of multifingered grasps with point contacts with friction.The proposed approach is based on the concept of programming by demonstration and interactive teaching, wherein an expert user provides in a teaching phase a set of exemplar grasps appropriate for the task. Following this phase, a representation of task-related grasps is built. During task planning and execution, a grasp could be either submitted interactively for evaluation by a non-expert user or synthesized by an automatic planning system. Grasp quality is then assessed based on the proposed measure, which takes into account grasp stability along with its suitability for the task. To enable real-time evaluation of grasps, a fast algorithm for computing an approximation of the quality measure is also proposed. Finally, a local grasp optimization technique is described which can amend uncertainties arising in supplied grasps by non-expert users or assist in planning more valuable grasps in the neighborhood of candidate ones.The paper reports experiments performed in virtual reality with both an anthropomorphic virtual hand and a three-fingered robot hand. These experiments suggest the effectiveness and task relevance of the proposed grasp quality measure.     

Malignant Transformation of Giant Cell Tumour of Bone: A Review of Literature and the Experience of a Referral Centre

Giant cell tumour of bone (GCTB) is a benign, locally aggressive primary bone neoplasm that represents 5% of all bone tumours. The principal treatment approach is surgery. Although generally GCTB is considered only a locally aggressive disease, it can metastasise, and lung metastases occur in 1–9% of patients. To date, only the use of denosumab has been approved as medical treatment for GCTB. Even more rarely, GCTB undergoes sarcomatous transformation into a malignant tumour (4% of all GCTB), but history of this malignant transformation is unclear and unpredictable. Considering the rarity of the event, the data in the literature are few. In this review, we summarise published data of GCTB malignant transformation and we analyse three cases of malignant transformation of GCTB, evaluating histopathology, genetics, and radiological aspects. Despite the rarity of this event, we conclude that a strict follow up is recommended to detect early malignant transformation.     

Complexity analysis of blast-induced vibrations in underground mining:A case study

Blasting in geological bodies is an industrial process acting in an environment characterized by high uncertainties (natural joints,faults,voids,abrupt structural changes),which are transposed into the...     

Recent progress in GeSi electro-absorption modulators

Electro-absorption from GeSi heterostructures is receiving growing attention as a high performance optical modulator for short distance optical interconnects. Ge incorporation with Si allows strong modulation mechanism using the Franz–Keldysh effect and the quantum-confined Stark effect from bulk and quantum well structures at telecommunication wavelengths. In this review, we discuss the current state of knowledge and the on-going challenges concerning the development of high performance GeSi electro-absorption modulators. We also provide feasible future prospects concerning this research topic.     

High Temperature Oxidation and Microstructural Evolution of Modified MCrAlY Coatings

Thermal sprayed MCrAlY coatings are widely used as a bond coat in thermal barrier systems to protect the substrate from corrosion and high temperature oxidation and to improve the compatibility between the ceramic top coat and metallic substrate. In this paper, the high temperature oxidation resistance of MCrAlY coatings with modified compositions was evaluated; in particular, the effect of the addition of reactive and refractory elements (Ta, Re, Si, and Hf) was investigated. MCrAlY coatings were obtained by high velocity oxygen fuel spray and vacuum plasma spray techniques; samples were exposed to air at 1423 K (1150 °C) and the oxidation kinetics were evaluated by measuring the thickness of the thermally grown oxide (TGO) scale at several exposure times. Experimental data confirmed that the oxidation resistance of MCrAlY coatings is strictly related to the amount of the reactive and refractory elements in the starting powders and that a thorough understanding of the microstructural modifications taking place during oxidation is essential for controlling TGO growth and thermal barriers’ durability.     

External Shape Differences between Sympatric Populations of Commercial Clams <Emphasis Type="Italic">Tapes decussatus</Emphasis> and <Emphasis Type="Italic">T. philippinarum</Emphasis>

The actual Italian production of clams is chiefly sustained by the native Tapes decussatus and the fortuitously imported Tapes philippinarum. Both species are commercialized as “Vongola verace”, but the commercial value of T. philippinarum is lower. The discrimination of species by sight is usually difficult and it cannot be done by observation based on shell morphology but only when animals open their valves hence displaying the two siphons. In this study, we propose a new, noninvasive method to discriminate individuals of both species based on the analysis of the external shape of their shells. Accordingly, in sympatric populations at two sites of the Po river outlet, we have chosen individuals (63 for T. decussatus and 57 for T. philippinarum) of comparable commercial size for which a certain genetic discrimination was previously done. Pictures of the left side valve were taken for all specimens. Their profiles were analyzed with the elliptic Fourier analysis. The mean outline for each species was graphically extracted. The coefficients of the harmonic equations were analyzed by multivariate classification (partial least squares discriminant analysis [PLSDA]). Results showed a high percentage of correct classification of individuals of both species (96.6%). Contour analysis reflected the overall shell shape and thus identified morphological aspects that were difficult to recognize and quantify in sight. The high percentage of correct classifications obtained by combining the analysis of elliptic Fourier harmonics with PLSDA demonstrated the feasibility of this method to discriminate species with a high level of resemblance.