Generation and selection of likely interpretations during plan recognition in task-oriented consultation systems

This paper presents a mechanism which infers a user's plans from his/her utterances by directing the inference process towards the more likely interpretations of a speaker's statements among many possible interpretations. Our mechanism uses Bayesian theory of probability to assess the likelihood of an interpretation, and it complements this assessment by taking into consideration two aspects of an interpretation: its coherence and its information content. The coherence of an interpretation is determined by the relationships between the different statements in the discourse. The information content of an interpretation is a measure of how well defined the interpretation is in terms of the actions to be performed on the basis of this interpretation. This measure is used to guide the inference process towards interpretations with higher information content. The information content of an interpretation depends on the specificity and the certainty of the inferences in it, where the certainty of an inference depends on the knowledge on which the inference is based. Our mechanism has been developed for use in task-oriented consultation systems. The particular domain that we have chosen for exploration is that of travel booking.     

Detection of failure sites by focused ion beam and nano-probing in the interconnect of three-dimensional stacked circuit structures

Focused ion beam (FIB) and nano-probing were applied for failure analysis of three-dimensional stacked circuits with copper through-silicon-vias between the stacked chips. The failure analysis was done after high temperature storage and thermal cycling tests. Passive voltage contrast in FIB allowed to pinpoint the open sites. FIB cross-sections showed the presence of opens at the bottom of the copper vias. The failure cause was suspected to be an interlayer particle, which was confirmed by optical profilometry. Nano-probing was used on another sample to pinpoint the failure location through the measurement of the local resistance within the daisy chains. The failure was traced out to be related with surface contamination.     

Natural convection from narrow horizontal plates at moderate Rayleigh numbers

The present work deals with the natural convection flow and heat transfer from a horizontal plate cooled from above. Experiments are carried out for rectangular plates having aspect ratios between φ=0.036 and 0.43 and Rayleigh numbers in the range 290?Ra_w?3.3×10⁵. These values of Ra_w and φ have been selected below those commonly considered in previous research in view of a future application to the design of printed circuit boards. The plates are made of two different metals, copper and steel. The choice of a metal is relevant to the present problem because the plates are heated by means of an electric current. Important variations of the surface temperature are observed along the transverse direction for the steel plates. The surface of the copper plates is almost isothermal because of the high thermal conductivity of the metal.Calculations for a semi-infinite plate are carried out to predict the transverse profiles of the surface temperature and heat flux and to visualize the structure of the flow. Three-dimensional calculations are also used at a qualitative level to observe the changes in the flow structure due to the finite length of the plate. Present results are compared with both previous experimental work and analyses that are based on boundary layer theory. It is shown that analyses for an infinite boundary layer are not completely applicable to the present problem because of its different physics. The most relevant feature of the natural convection flow, which is not predicted by boundary layer analyses, is a thermal plume rising near the center of the plate.Present heat transfer results differ from previous experimental work because of the lower Rayleigh numbers and aspect ratios investigated here. The Nusselt number is found to depend on Ra_wⁿ, with the exponent n=0.17 being lower than most of the values reported in the literature. This comparatively low value is related to the transverse conduction of heat through the air, which becomes increasingly significant as Ra_w approaches zero. It is shown that such a low-Ra_w effect can be accounted for in a physically consistent manner by adding a constant term to the heat transfer correlation. On the other hand, it is found that the Nusselt number does not significantly depend on the aspect ratio in the range of φ investigated contrary to what has been previously reported for wider plates.     

The effect of Cu-rich sub-layer on the increased corrosion resistance of Cu-xZn alloys in chloride containing borate buffer

The electrochemical behaviour of Cu-xZn alloys, as well as their constituent metals, in a borate buffer containing chloride ions in the molar range from 0.01 to 1 M are studied. Characteristics of these materials under anodic polarization are compared and the composition and morphology of the corrosion products formed in the course of polarization experiment are analysed by SEM and EDS. X-ray photoelectron spectroscopy and electrochemical impedance measurements are used for characterization of the surface layers formed on Cu, Zn and Cu-40Zn alloy during 2-h immersion at E_oc in a borate buffer containing two different concentrations of chloride ions. New aspects of the behaviour of brass under E_oc condition are revealed. The improved corrosion resistance of brass in chloride media, if compared to zinc metal, is attributed to a Cu-rich layer formed by the selective dissolution of zinc. Based on the results, a structural model describing the improved corrosion resistance of Cu-40Zn alloy with respect to Zn metal is proposed.     

Complement-Opsonized Nano-Carriers Are Bound by Dendritic Cells (DC) via Complement Receptor (CR)3, and by B Cell Subpopulations via CR-1/2, and Affect the Activation of DC and B-1 Cells

The development of nanocarriers (NC) for biomedical applications has gained large interest due to their potential to co-deliver drugs in a cell-type-targeting manner. However, depending on their surface characteristics, NC accumulate serum factors, termed protein corona, which may affect their cellular binding. We have previously shown that NC coated with carbohydrates to enable biocompatibility triggered the lectin-dependent complement pathway, resulting in enhanced binding to B cells via complement receptor (CR)1/2. Here we show that such NC also engaged all types of splenic leukocytes known to express CR3 at a high rate when NC were pre-incubated with native mouse serum resulting in complement opsonization. By focusing on dendritic cells (DC) as an important antigen-presenting cell type, we show that CR3 was essential for binding/uptake of complement-opsonized NC, whereas CR4, which in mouse is specifically expressed by DC, played no role. Further, a minor B cell subpopulation (B-1), which is important for first-line pathogen responses, and co-expressed CR1/2 and CR3, in general, engaged NC to a much higher extent than normal B cells. Here, we identified CR-1/2 as necessary for binding of complement-opsonized NC, whereas CR3 was dispensable. Interestingly, the binding of complement-opsonized NC to both DC and B-1 cells affected the expression of activation markers. Our findings may have important implications for the design of nano-vaccines against infectious diseases, which codeliver pathogen-specific protein antigen and adjuvant, aimed to induce a broad adaptive cellular and humoral immune response by inducing cytotoxic T lymphocytes that kill infected cells and pathogen-neutralizing antibodies, respectively. Decoration of nano-vaccines either with carbohydrates to trigger complement activation in vivo or with active complement may result in concomitant targeting of DC and B cells and thereby may strongly enhance the extent of dual cellular/humoral immune responses.     

Exogenous Integrin αIIbβ3 Inhibitors Revisited: Past,Present and Future Applications

The integrin αIIbβ3 is the most abundant integrin on platelets. Upon platelet activation, the integrin changes its conformation (inside-out signalling) and outside-in signalling takes place leading to platelet spreading, platelet aggregation and thrombus formation. Bloodsucking parasites such as mosquitoes, leeches and ticks express anticoagulant and antiplatelet proteins, which represent major sources of lead compounds for the development of useful therapeutic agents for the treatment of haemostatic disorders or cardiovascular diseases. In addition to hematophagous parasites, snakes also possess anticoagulant and antiplatelet proteins in their salivary glands. Two snake venom proteins have been developed into two antiplatelet drugs that are currently used in the clinic. The group of proteins discussed in this review are disintegrins, low molecular weight integrin-binding cysteine-rich proteins, found in snakes, ticks, leeches, worms and horseflies. Finally, we highlight various oral antagonists, which have been tested in clinical trials but were discontinued due to an increase in mortality. No new αIIbβ3 inhibitors are developed since the approval of current platelet antagonists, and structure-function analysis of exogenous disintegrins could help find platelet antagonists with fewer adverse side effects.     

SUL-151 Decreases Airway Neutrophilia as a Prophylactic and Therapeutic Treatment in Mice after Cigarette Smoke Exposure

Chronic obstructive pulmonary disease (COPD) caused by cigarette smoke (CS) is featured by oxidative stress and chronic inflammation. Due to the poor efficacy of standard glucocorticoid therapy, new treatments are required. Here, we investigated whether the novel compound SUL-151 with mitoprotective properties can be used as a prophylactic and therapeutic treatment in a murine CS-induced inflammation model. SUL-151 (4 mg/kg), budesonide (500 μg/kg), or vehicle were administered via oropharyngeal instillation in this prophylactic and therapeutic treatment setting. The number of immune cells was determined in the bronchoalveolar lavage fluid (BALF). Oxidative stress response, mitochondrial adenosine triphosphate (ATP) production, and mitophagy-related proteins were measured in lung homogenates. SUL-151 significantly decreased more than 70% and 50% of CS-induced neutrophils in BALF after prophylactic and therapeutic administration, while budesonide showed no significant reduction in neutrophils. Moreover, SUL-151 prevented the CS-induced decrease in ATP and mitochondrial mtDNA and an increase in putative protein kinase 1 expression in the lung homogenates. The concentration of SUL-151 was significantly correlated with malondialdehyde level and radical scavenging activity in the lungs. SUL-151 inhibited the increased pulmonary inflammation and mitochondrial dysfunction in this CS-induced inflammation model, which implied that SUL-151 might be a promising candidate for COPD treatment.