Advanced information processing system: Input/output system services

The functional requirements and detailed specifications for the Input/Output (I/O) Systems Services of the Advanced Information Processing System (AIPS) are discussed. The introductory section is provided to outline the overall architecture and functional requirements of the AIPS system. Section 1.1 gives a brief overview of the AIPS architecture as well as a detailed description of the AIPS fault tolerant network architecture, while section 1.2 provides an introduction to the AIPS systems software. Sections 2 and 3 describe the functional requirements and design and detailed specifications of the I/O User Interface and Communications Management modules of the I/O System Services, respectively. Section 4 illustrates the use of the I/O System Services, while Section 5 concludes with a summary of results and suggestions for future work in this area

Characterization of an in vitro 3D Human Small Airway Epithelia model for the application of integrated strategies in inhaled drug development

Drug Inhalation is one of the most effective administration routes; in fact, first pass metabolism is bypassed, rapid action onset is enabled and drug doses can be kept relatively low compared to other administration routes. The most recent 3D in vitro models allow to mimic some of the pulmonary tissue functionalities. These models reproduce the air-liquid interface, with beating cilia and mucus production, since different types of cells are present. Therefore, these models could be possibly applied to multi-disciplinary investigations following liquid, dry powder or aerosol treatment. In this thesis, an integrated strategy is proposed, with the aim to increase the rate of success in the drug candidate selection phase. Ideally, safety data should be integrated with early pharmacokinetics (PK) and efficacy indications in order to increase chances to select the candidate with the highest safety margins. With this ambitious objective in mind, a human-based 3D model were evaluated as model for the toxicity assessment and drug permeability evaluation. In particular, a commercially available 3D respiratory model SmallAir\u2122 has been qualified for: a) sensibility and specificity in the evaluation of lung toxicity potential of new compounds; b) permeability to test drug transport through tissues for formulation screening purposes; c) quantitative cytokine secretion on cell supernatant; d) cilia beating and muco-ciliary clearance evaluation by image analysis. These tests performed on a human tissue could provide more reliable results also because all tests were performed in the same model and this could be helpful in data integration. This approach could allow to fill gaps in drug discovery for human-relevant screening of new chemical entities (NCEs), best formulation selection, including physiochemical equivalence evaluation generic drug development. In vitro and in silico data can be helpful in predicting PK and toxicity profiles prior to preclinical and clinical studies. This allows to respect the 3Rs principle of replacement, reduction and refinement of in vivo studies. The proposed integrated testing strategy (ITS) has the potential to reduce the attrition in drug development, to optimize the inhaled formulation, to screen compounds for candidate selection and to reduce in vivo studies.For the toxicity tests, well-known respiratory toxic compound were tested both in the SmallAir\u2122 model and in the A549 cell line model. On the basis of results, the SmallAir\u2122 model seemed to be less sensitive than A549, probably due to the 3D structure physiological features. Cilia beating and mucus production can indeed protect the cells from the toxic effect miming the in vivo response. For the permeability study, well-known inhalation compounds with very different permeability values were evaluated both in SmallAir\u2122 model and in the standard Caco2 cell model. For low and high permeable compounds results obtained were comparable in the two test considered systems. The most evident difference was observed with medium permeable compounds, suggesting that the SmallAir\u2122 model should express different efflux pumps on their surface form the standard Caco2 cell model. The SmallAir\u2122 model was also evaluated as in vitro model for the inflammatory mediators assessment. The treatment with TGF-\u3b2 allowed to confirm the activation of the signalling via Smad2 while, inconclusive results were obtained with regards to cytokines and ROS release following Bleomycin treatment. The SmallAir\u2122 model was finally evaluated as in vitro model for the assessment of the Muco-ciliary Clearance (MCC). Results obtained in this project, showed that the SmallAir\u2122 can be a promising model to assess the MCC in vitro after treatment with compound acting on ATP release and Cystic fibrosis transmembrane conductance Inhibitor-172 (CFTR172inh). More test considering different compound, study design and end points has to be conducted, in order to identify a human relevant in vitro lung model to be applied in many fields of analysis

Knowledge representation into Ada parallel processing

The Knowledge Representation into Ada Parallel Processing project is a joint NASA and Air Force funded project to demonstrate the execution of intelligent systems in Ada on the Charles Stark Draper Laboratory fault-tolerant parallel processor (FTPP). Two applications were demonstrated - a portion of the adaptive tactical navigator and a real time controller. Both systems are implemented as Activation Framework Objects on the Activation Framework intelligent scheduling mechanism developed by Worcester Polytechnic Institute. The implementations, results of performance analyses showing speedup due to parallelism and initial efficiency improvements are detailed and further areas for performance improvements are suggested

Advanced information processing system: Fault injection study and results

The objective of the AIPS program is to achieve a validated fault tolerant distributed computer system. The goals of the AIPS fault injection study were: (1) to present the fault injection study components addressing the AIPS validation objective; (2) to obtain feedback for fault removal from the design implementation; (3) to obtain statistical data regarding fault detection, isolation, and reconfiguration responses; and (4) to obtain data regarding the effects of faults on system performance. The parameters are described that must be varied to create a comprehensive set of fault injection tests, the subset of test cases selected, the test case measurements, and the test case execution. Both pin level hardware faults using a hardware fault injector and software injected memory mutations were used to test the system. An overview is provided of the hardware fault injector and the associated software used to carry out the experiments. Detailed specifications are given of fault and test results for the I/O Network and the AIPS Fault Tolerant Processor, respectively. The results are summarized and conclusions are given

Advanced information processing system: Inter-computer communication services

The purpose is to document the functional requirements and detailed specifications for the Inter-Computer Communications Services (ICCS) of the Advanced Information Processing System (AIPS). An introductory section is provided to outline the overall architecture and functional requirements of the AIPS and to present an overview of the ICCS. An overview of the AIPS architecture as well as a brief description of the AIPS software is given. The guarantees of the ICCS are provided, and the ICCS is described as a seven-layered International Standards Organization (ISO) Model. The ICCS functional requirements, functional design, and detailed specifications as well as each layer of the ICCS are also described. A summary of results and suggestions for future work are presented

Infrastructural projects and territorial development in Veneto Dolomites: Evaluation of performances through AHP

Abstract The ensemble of European traffic roads is changing in relation to the economic geography that has been developing these recent years and also to the localisation of production centres, logistics and the demand linked to the transportation of goods. The development of communication has been defined through the project of the Trans-European Transport Network (TEN-T). This network has been progressively defined until it has reached the present architecture in which Italy is crossed by four of the nine total corridors that compose the whole network - which means by almost half of the main traffic roads at European level -. Undoubtedly this new geography of European communication offers member States new development opportunities, but it is also true that the distance of the different territories from the major traffic roads can be a disparity factor. In fact, this phenomenon can worsen the marginalisation processes of some European territories, contrary to the objective of the interconnection policy of the EU territories. In front of these possible territorial disparities, the Planning discipline in Italy has not been adequately questioned, aiming instead at the research of the "territorial patching up", progressively decreasing, rather than at the exploration of new development forms. As a consequence, mobility planning becomes strategic for Italy, especially for its Alpine area. Hence the need to set up valid tools for the environmental evaluation as regards planning and programmes, such as the Strategic Environmental Assessment (SEA), but also projects, as the Environmental Impact Assessment (EIA). The idea to realise an important road infrastructure, which may connect Belluno directly with Austria, is presented in this paper as an emblematic case, in which the application of the Analytic Hierarchy Process (AHP) permits to verify the best performing infrastructure on a territorial scale

Is endoscopic inspection necessary to detect residual disease in acoustic neuroma surgery?

Main goals: To analyze how and when the endoscope is used in vestibular schwannoma surgery and identify the benefits of using endoscopy in this type of surgery. Background: It is currently unclear if there is any benefit from using an endoscope in vestibular schwannoma surgery so this retrospective analysis set out to study this. Methods: All the patients who underwent vestibular schwannoma surgery at our clinic were included for all the vestibular schwannoma approaches taken. We studied when endoscopy was used during surgery and the goal of using endoscopy. Several pre- and postoperative factors were assessed such as complications, facial function, and hearing function in the case of techniques that allow hearing preservation. Results: From January 2015 to September 2018, 280 patients underwent lateral skull base surgery. Of these, 112 were included in this study. The endoscope was used in all 112 patients, and in eight cases it was possible to identify residual disease using the endoscope to check the surgical field, and then to remove the disease under endoscopic view. Moreover, in two other cases, the endoscope was used to resolve a vasculoneural conflict between the anterior inferior cerebellar artery (AICA) loop and facial nerve in one case, and for deafferentation of the superior and inferior vestibular nerves in the second case. No major intraoperative complications occurred in our series. There was no statistically significant difference in postoperative facial nerve function between patients in whom the endoscope was used as a diagnostic tool and patients in whom it was used as an operative tool (p = 0.3152). Conclusions: The endoscope may be useful, especially in surgical techniques where there is poor control of the internal auditory canal (IAC). An endoscopic support technique is strongly recommended to avoid residual disease, particularly in retrosigmoid and retrolabyrinthine approaches. Moreover, the recent introduction of the transcanal transpromontorial approach allows the endoscope to be used during all the procedures in patients affected by a vestibular schwannoma limited to the IAC or to support surgical procedures during an enlarged microscopic approach

Exclusive endoscopic transcanal transpromontorial approach: a new perspective for internal auditory canal vestibular schwannoma treatment

OBJECTIVE The aim of this study was to describe the first case series in which an exclusive endoscopic transcanal transpromontorial approach (EETTA) was used to treat small vestibular schwannomas (VSs) and meningiomas of the internal auditory canal (IAC). METHODS The authors performed a retrospective review of patients who had undergone surgery using an EETTA to the IAC at 2 university tertiary care referral centers during the period from November 2011 to January 2015. RESULTS Ten patients underwent surgery via an EETTA for the treatment of VS in the IAC at the University Hospital of Modena or the University Hospital of Verona. The patients had Koos Grade I or II tumors and American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS) Class D hearing status preoperatively. Gross-total resection was achieved in all patients. No major complications such as cerebrospinal fluid leakage or hemorrhage were reported. In 7 of 10 (70%) patients, facial nerve function was normal immediately after surgery (Rough Grading System [RGS] Grade I). Two patients presented with a transitory facial palsy immediately after surgery (RGS Grade II-III) but experienced complete recovery during the follow-up period. The mean follow-up was 10 months. CONCLUSIONS The EETTA proved to be successful for the removal of VS or meningioma involving the cochlea, fundus, and IAC, with possible lower complication rates and less invasive procedures than those for traditional microscopic approaches. The potential for the extensive and routine use of this approach in lateral and posterior skull base surgery will depend on the development of technology and surgical refinements and on the diffusion of skull base endoscopic skills among the otolaryngological and neurosurgical communities