Prion protein amyloidosis

The prion protein (PrP) plays an essential role in the pathogenesis of a group of sporadic, genetically determined and infectious fatal degenerative diseases, referred to as "prion diseases", affecting the central nervous system of humans and other mammals. The cellular PrP is encoded by a single copy gene, highly conserved across mammalian species. In prion diseases, PrP undergoes conformational changes involving a shift from alpha-helix to beta-sheet structure. This conversion is important for PrP amyloidogenesis, which occurs to the highest degree in the genetically determined Gerstmann-Str?ussler-Scheinker disease (GSS) and prion protein cerebral amyloid angiopathy (PrP-CAA), while it is less frequently seen in other prion diseases. GSS and PrP-CAA are associated with point mutations of the prion protein gene (PRNP); these conditions show a broad spectrum of clinical presentation, the main signs being ataxia, spastic paraparesis, extrapyramidal signs and dementia. In GSS, parenchymal amyloid may be associated with spongiform changes or neurofibrillary lesions; in PrP-CAA, vascular amyloid is associated with neurofibrillary lesions. A major component of the amyloid fibrils in the two diseases is a 7 kDa peptide, spanning residues 81-150 of PrP.     

Design and control of next generation distribution frames

In today’s access networks, the permutation of circuits connecting the subscriber lines to Plain Old Telephone Service (POTS) and to Digital Subscriber Line Access Multiplexers (DSLAMs) occurs in the Main Distribution Frame (MDF) and is still manually configured. However, new market regulations and new policies adopted by operators require increasingly more frequent permutations, making the manual configuration activity particularly expensive. Very recently, Automated MDFs (AMDFs) have been developed to provide inexpensive and almost real-time switching capability. Our study, based on more than 50 years of research activities on architectures for circuit switching, is focused on overcoming the limits of classical architectures. In fact, strictly non-blocking multistage networks are too expensive, as a consequence of the large number of ports they require (sometimes exceeding 100,000). In addition, rearrangeable multistage networks can temporarily interrupt active circuits, affecting the performance of ADSL subscriber lines.As a possible solution to these problems, we propose the design of AMDFs based on Non-Interruptive Rearrangeable (NIR) networks. We show how to optimize the routing control to minimize the setup time of a circuit and to exploit output grouping. We believe that the solution described above is not only relevant for the theory of multistage interconnection networks, but also for the design and operation of large AMDFs.     

Throughput Region of Finite-Buffered Networks

Most of the current communication networks, including the Internet, are packet switched networks. One of the main reasons behind the success of packet switched networks is the possibility of performance gain due to multiplexing of network bandwidth. The multiplexing gain crucially depends on the size of the buffers available at the nodes of the network to store packets at the congested links. However, most of the previous work assumes the availability of infinite buffer-size. In this paper, we study the effect of finite buffer-size on the performance of networks of interacting queues. In particular, we study the throughput of flow-controlled loss-less networks with finite buffers. The main result of this paper is the characterization of a dynamic scheduling policy that achieves the maximal throughput with a minimal finite buffer at the internal nodes of the network under memory-less (e.g., Bernoulli IID) exogenous arrival process. However, this ideal performance policy is rather complex and, hence, difficult to implement. This leads us to the design of a simpler and possibly implementable policy. We obtain a natural trade-off between throughput and buffer-size for such implementable policy. Finally, we apply our results to packet switches with buffered crossbar architecture     

Role of recombinant interferon-gamma maintenance in responding patients with small cell lung cancer. A randomised phase III study of the EORTC Lung Cancer Cooperative Group

This study was undertaken to determine if recombinant interferon-gamma (rIFN-gamma) given every other day as maintenance therapy could prolong the survival of patients with small cell lung cancer (SCLC) who achieved a complete or nearly-complete response to induction therapy. A secondary endpoint was to assess the toxicity of alternate day doses of this treatment. One hundred and seventy seven patients in complete or nearly-complete response following chemotherapy with or without thoracic radiotherapy were studied. Patients were randomised to receive either rIFN-gamma 4 million units (0.2 mg) subcutaneously every other day for 4 months or observation. One hundred and twenty of the 127 registered patients were eligible; 59 patients received IFN and 61 patients without maintenance therapy were followed. Alternate day IFN was reasonably well tolerated by the majority of patients, but in 12% substantial non-haematological toxicity (including flu-like syndrome) occurred. One of 3 patients with pneumonitis died after having received 3.6 mg IFN. The median survival time from the date of randomisation was 8.9 months for the IFN arm and 9.9 months for the observation arm. rIFN-gamma at the dose and schedule used in this study failed to prolong response duration and survival in SCLC patients in complete or nearly-complete response. The toxicity seen with every other day doses of IFN was less than that reported with daily dosing. The hypothesis that this agent may increase the deleterious effects of radiation on normal lung tissue was supported by the development of pneumonitis in 3 cases of whom 1 had a fatal outcome. The results do not warrant further studies with rIFN-gamma on maintaining response in SCLC.