Meta-evaluation of Actors with Side-effects

This report describes research done at the Artificial Intelligence Laboratory of the Massachusetts Institute of Technology. Support for the laboratory's artificial intelligence research is provided in part by the Advanced Research Projects Agency of the Department of Defense under Office of Naval Research contract N000-14-74-C-0643.Meta-evaluation is a process which symbolically evaluates an actor and checks to see whether the actor fulfills its contract (specification). A formalism for writing contracts for actors with side-effects which allow sharing of data is presented. Typical examples of actors with side-effects are the cell, actor counterparts of the LISP function rplaca and rplacd, and procedures whose computation depends upon their input history. Meta-evaluation of actors with side-effects is carried out by using situational tags which denotes a situation (local state of an actor systems at the moment of the transmissions of messages). It is illustrated how the situational tags are used for proving the termination of the activation of actors.MIT Artificial Intelligence Laborator

Symbol IC-Evaluation as an Aid to Program Synthesis

This report describes research done at the Artificial Intelligence laboratory of the Massachusetts Institute of Technology. Support for the laboratory's artificial intelligence research is provided in part by the Advance Research Projects Agency of the Department of Defence under Office of Naval Research contract N00014-75-C0522.Symbolic-evaluation is the process which abstractly evaluates an actor program and checks to see whether the program fulfills its contract (specification). In this paper, a formalism based on the conceptual representation is proposed as a specification language and a proof system for programs which may include change of behavior (side-effects). The relation between algebraic specifications and the specifications based on the conceptual representation is discussed and the limitation of the current algebraic specifications is pointed out. The proposed formalism can deal with problems of side-effects which have been beyond the scope of Floyd-Hoare proof rules. Symbolic-evaluation is carried out with explicit use of the notion of situation (local state of an actor system). Uses of situational tags in assertions make it possible to state relations holding between objects in different situations. As an illustrative example, an impure actors which behave like a queue is extensively examined. The verification of a procedure which deals with the queue-actors and the correctness of its implementations are demonstrated by the symbolic-evaluation. Furthermore how the symbolic-evaluation serves as an aid to program synthesis is illustrated using two different implementations of the queue-actor.MIT Artificial Intelligence Laboratory Department of Defense Advanced Research Projects Agenc

An Object-Oriented Model for Extensible Concurrent Systems: the Composition-Filters Approach

Applying the object-oriented paradigm for the development of large and complex software systems offers several advantages, of which increased extensibility and reusability are the most prominent ones. The object-oriented model is also quite suitable for modeling concurrent systems. However, it appears that extensibility and reusability of concurrent applications is far from trivial. The problems that arise, the so-called inheritance anomalies are analyzed and presented in this paper. A set of requirements for extensible concurrent languages is formulated. As a solution to the identified problems, an extension to the object-oriented model is presented; composition filters. Composition filters capture messages and can express certain constraints and operations on these messages, for example buffering. In this paper we explain the composition filters approach, demonstrate its expressive power through a number of examples and show that composition filters do not suffer from the inheritance anomalies and fulfill the requirements that were established

Abstracting object interactions using composition filters

It is generally claimed that object-based models are very suitable for building distributed system architectures since object interactions follow the client-server model. To cope with the complexity of today's distributed systems, however, we think that high-level linguistic mechanisms are needed to effectively structure, abstract and reuse object interactions. For example, the conventional object-oriented model does not provide high-level language mechanisms to model layered system architectures. Moreover, we consider the message passing model of the conventional object-oriented model as being too low-level because it can only specify object interactions that involve two partner objects at a time and its semantics cannot be extended easily. This paper introduces Abstract Communication Types (ACTs), which are objects that abstract interactions among objects. ACTs make it easier to model layered communication architectures, to enforce the invariant behavior among objects, to reduce the complexity of programs by hiding the interaction details in separate modules and to improve reusability through the application of object-oriented principles to ACT classes. We illustrate the concept of ACTs using the composition filters model

Discriminative application of string similarity methods to chemical and non-chemical names for biomedical abbreviation clustering

BACKGROUND: Various computational methods are presently available to classify whether a protein variation is disease-associated or not. However data derived from recent technological advancements make it feasible to extend the annotation of disease-associated variations in order to include specific phenotypes. Here we tackle the problem of distinguishing between genetic variations associated to cancer and variations associated to other genetic diseases. RESULTS: We implement a new method based on Support Vector Machines that takes as input the protein variant and the protein function, as described by its associated Gene Ontology terms. Our approach succeeds in discriminating between germline variants that are likely to be cancer-associated from those that are related to other genetic disorders. The method performs with values of 90% accuracy and 0.61 Matthews correlation coefficient on a set comprising 6478 germline variations (16% are cancer-associated) in 592 proteins. The sensitivity and the specificity on the cancer class are 69% and 66%, respectively. Furthermore the method is capable of correctly excluding some 96% of 3392 somatic cancer-associated variations in 1983 proteins not included in the training/testing set. CONCLUSIONS: Here we prove feasible that a large set of cancer associated germline protein variations can be successfully discriminated from those associated to other genetic disorders. This is a step further in the process of protein variant annotation. Scoring largely improves when protein function as encoded by Gene Ontology terms is considered, corroborating the role of protein function as a key feature for a correct annotation of its variations

Zinc-pyrithione exerts diverse actions on human leukemia K562 cells : A preliminary study on hormetic action

Zinc-pyrithione is widely used as a topical agent. It may be likely that zinc-pyrithione possesses unique cytotoxic action because zinc exerts diverse actions on process of cell death. In this study, we examined the cytotoxicity of zinc-pyrithione on human leukemia K562 cells in order to examine the possibility of hormetic action. Zinc-pyrithione at concentrations ranging from 0.3 μM to 3 μM induced diverse actions on K562 cells. The agent at 0.3 and 1 μM significantly inhibited spontaneous occurrence of cell death during 72 h incubation while it was not the case for 3 μM. Significant decrease in population of shrunken cells was observed when the concentrations of zinc-pyrithione were 0.3 and 1 μM. Cell growth was significantly inhibited by 1 and 3 μM zinc-pyrithione, but not by 0.3 μM. Although the inhibition of cell growth by zinc-pyrithione was concentration-dependent, the inhibition of spontaneous cell death was observed only at lower concentrations (0.3 and 1 μM) of zinc-pyrithione. Results suggest that zinc-pyrithione possesses diverse actions, including hormetic action, on proliferative cells

Doppler ultrasound findings correlate with tissue vascularity and inflammation in surgical pathology specimens from patients with small intestinal Crohn’s disease

BACKGROUND: Crohn’s disease (CD) is routinely evaluated using clinical symptoms, laboratory variables, and the CD activity index (CDAI). However, clinical parameters are often nonspecific and do not precisely reflect the actual activity of CD small-intestinal lesions. The purposes of this prospective study were to compare color Doppler ultrasound (US) findings with histological findings from surgically resected specimens and confirm the hypothesis that color Doppler US can distinguish tissue inflammation and fibrosis. METHODS: Among 1764 consecutive patients who underwent color Doppler US examinations, 10 patients with CD (12 small-intestinal CD lesions) who underwent US examinations before elective small-intestine resection were evaluated in the present study. Areas of thickened intestinal walls were evaluated in terms of blood flow using color Doppler US imaging. The blood flow was semiquantitatively classified as “hyper-flow” and “hypo-flow” according to the Limberg score. Resected lesions were macroscopically and histopathologically processed. Inflammatory cell infiltration, fibrosis and vascularity were evaluated by myeloperoxidase (granulocytes), CD163 (macrophages), CD79a (B cells), CD3 (T cells), Masson’s trichrome (fibrosis), and factor VIII staining (vascular walls). All histopathological images were entered into virtual slide equipment and quantified using a quantitative microscopy integrated system (TissueMorph™). RESULTS: There were no significant differences in disease features or laboratory findings between “hypo-flow” lesions (n = 4) and “hyper-flow” lesions (n = 8). Histopathologically, “hyper-flow” lesions showed significantly greater bowel wall vascularity (factor VIII) (p = 0.047) and inflammatory cell infiltration, including CD163 macrophages (p = 0.008), CD3 T cells, and CD79a B cells (p = 0.043), than did “hypo-flow” lesions. There was no apparent association between the blood flow and CDAI. CONCLUSIONS: In this study, active CD lesions were macroscopically visible in surgical specimens of patients with increased blood flow on preoperative color Doppler US imaging. Additionally, these CD lesions exhibited significantly greater vascularity and numbers of inflammatory leukocytes microscopically. Color Doppler US may predict tissue inflammation and fibrosis in small-intenstinal CD lesions