New strategic goals and organizational solutions in large R&D labs: lessons from Centro Ricerche Fiat and Telecom Italia Lab

The issue of corporate R&D management has become particularly relevant during the last decade, since many industrial sectors experienced growing complexity in their research areas and increasing constraints in budgets devoted to R&D activities. This paper discusses the cases of the ICT and automotive sectors, exploring the changes in managerial procedures and strategies that two of the largest corporate research centres in Italy (Telecom Italia Lab and Centro Ricerche Fiat) adopted during a delicate phase of transition. Both cases are characterized by a growing pressure towards the effective integration of short-term and long-term perspectives, i.e. towards a balance between valorization of research results and competencies, and exploration of new technological trajectories. The solutions adopted by the two organizations are explored and discussed. Specifically, while TiLab focused on the promotion of controlled spin-off companies, CRF has been very active in local technology transfer, especially in favour of SMFs

Firing rate optimization of cyclic timed event graphs by token allocations

In this paper, we deal with the problem of allocating a given number of tokens in a cyclic timed event graph (CTEG) so as to maximize the firing rate of the net. We propose three different approaches. The first one is a "greedy" incremental procedure that is computationally very efficient. The only drawback is that the convergence to the optimum is guaranteed only when the set of places where tokens can be allocated satisfies given constraints. The other two procedures involve the solution of a mixed integer linear programming problem. The first one needs the knowledge of the elementary circuits, thus it is convenient only for those classes of CTEG whose number of elementary circuits is roughly equal to the number of places, such as some kanban-systems. On the contrary, the second one enables one to overcome this difficulty, thus providing an efficient tool for the solution of allocation problems in complex manufacturing systems like job-shop systems

Magnetic properties of cobalt ferrite-silica nanocomposites prepared by a sol-gel autocombustion technique

The magnetic properties of cobalt ferrite-silica nanocomposites with different concentrations (15, 30, and 50 wt %) and sizes (7, 16, and 28 nm) of ferrite particles have been studied by static magnetization measurements and Mossbauer spectroscopy. The results indicate a superparamagnetic behavior of the nanoparticles, with weak interactions slightly increasing with the cobalt ferrite content and with the particle size. From high-field Mossbauer spectra at low temperatures, the cationic distribution and the degree of spin canting have been estimated and both parameters are only slightly dependent on the particle size. The magnetic anisotropy constant increases with decreasing particle size, but in contrast to many other systems, the cobalt ferrite nanoparticles are found to have an anisotropy constant that is smaller than the bulk value. This can be explained by the distribution of the cations. The weak dependence of spin canting degree on particle size indicates that the spin canting is not simply a surface phenomenon but also occurs in the interiors of the particles. (c) 2006 American Institute of Physics

Pathobiology of ALK-negative anaplastic large cell lymphoma

The authors revise the concept of ALK-negative anaplastic large cell lymphoma (ALCL) in the light of the recently updated WHO classification of Tumors of Hematopoietic and Lymphoid Tissues both on biological and clinical grounds. The main histological findings are illustrated as well as the phenotypic, molecular and clinical characteristics. Finally, the biological rationale for possible innovative targeted therapies is presented

Molecular Profiling of Aggressive Lymphomas

In the last years, several studies of molecular profiling of aggressive lymphomas were performed. In particular, it was shown that DLBCL can be distinguished in two different entities according to GEP. Specifically, ABC and GCB subtypes were characterized by having different pathogenetic and clinical features. In addition, it was demonstrated that DLBCLs are distinct from BL. Indeed, the latter is a unique molecular entity. However, relevant pathological differences emerged among the clinical subtypes. More recently, microRNA profiling provided further information concerning BL-DLBCL distinction as well as for their subclassification. In this paper, the authors based on their own experience and the most updated literature review, the main concept on molecular profiling of aggressive lymphomas

Transcriptional Analysis of Lennert Lymphoma Reveals a Unique Profile and Identifies Novel Therapeutic Targets

Lennert lymphoma (LL) is a lymphoepithelioid morphological variant of peripheral T-cell lymphoma—not otherwise specified (PTCL/NOS), clinically characterized by better prognosis if compared with other PTCL/NOS. Although well characterized as far as morphology and phenotype are concerned, very little is known regarding its molecular features. In this study, we investigated the transcriptional profile of this tumor aiming 1) to identify its cellular counterparts; 2) to better define its relation with other PTCLs—and, therefore, its possible position in lymphoma classification; and 3) to define pathogenetic mechanisms, possibly unveiling novel therapeutic targets. To address these issues, we performed gene and microRNA expression profiling on LL and other PTCL/NOS cases; we identified different genes and microRNAs that discriminated LL from other PTCL/NOS. Particularly, LL revealed a molecular signature significantly enriched in helper function and clearly distinguishable from other PTCL/NOS. Furthermore, PI3K/Akt/mTOR pathway emerged as novel potential therapeutic target. In conclusion, based on the already known particular morphological and clinical features, the new molecular findings support the hypothesis that LL might be classified as a separate entity. Preclinical and clinical studies testing the efficacy of PI3K/MTOR inhibitors in this setting are warranted

Hodgkin's lymphoma: The pathologist's viewpoint

Despite its well known histological and clinical features, Hodgkin's lymphoma (HL) has recently been the object of intense research activity, leading to a better understanding of its phenotype, molecular characteristics, histogenesis, and possible mechanisms of lymphomagenesis. There is complete consensus on the B cell derivation of the tumour in most cases, and on the relevance of Epstein-Barr virus infection and defective cytokinesis in at least a proportion of patients. The REAL/WHO classification recognises a basic distinction between lymphocyte predominance HL (LP-HL) and classic HL (CHL), reflecting the differences in clinical presentation and behaviour, morphology, phenotype, and molecular features. CHL has been classified into four subtypes: lymphocyte rich, nodular sclerosing, with mixed cellularity, and lymphocyte depleted. The borders between CHL and anaplastic large cell lymphoma have become sharper, whereas those between LP-HL and T cell rich B cell lymphoma remain ill defined. Treatments adjusted to the pathobiological characteristics of the tumour in at risk patients have been proposed and are on the way to being applied

Pathobiology of Anaplastic Large Cell Lymphoma

The authors revise the concept of anaplastic large cell lymphoma (ALCL) in the light of the recently updated WHO classification of Tumors of Hematopoietic and Lymphoid Tissues both on biological and clinical grounds. The main histological findings are illustrated with special reference to the cytological spectrum that is indeed characteristic of the tumor. The phenotype is reported in detail: the expression of the ALK protein as well as the chromosomal abnormalities is discussed with their potential pathogenetic implications. The clinical features of ALCL are presented by underlining the difference in terms of response to therapy and survival between the ALK-positive and ALK-negative forms. Finally, the biological rationale for potential innovative targeted therapies is presented

Gene expression profile predicts response to the combination of tosedostat and low-dose cytarabine in elderly AML

Tosedostat is an orally administered metalloenzyme inhibitor with antiproliferative and antiangiogenic activity against hematological and solid human cancers. Clinical activity has been demonstrated in relapsed acutemyeloid leukemia (AML). Thirty-three elderly patients with AML (median age, 75 years) received 120mgtosedostat orally once daily combinedwith subcutaneous low-dose cytarabine (20 mg twice per day for 10 days, up to 8 cycles), until disease progression. Inductionmortality was 12%. According to an intention-to-treat analysis, the complete remission (CR) rate was 48.5%, and thus the primary end point of the study was reached (expected CR, 25%). The partial remission rate was 6.1%,with an overall response rate of 54.5%. Furthermore, 4 of 33 patients had stable disease (median: 286 days). Themedian progression-free survival and overall survival (OS)were 203 days and 222 days, respectively. Responding patients had a longer median OS than nonresponding patients (P=.001). Amicroarray analysis performed in 29 of 33 patients identified 188 genes associated with clinical response (CR vs no CR). Three of them (CD93, GORASP1, CXCL16) were validated by quantitative polymerase chain reaction, which correctly classified 83% of the patients. Specifically, CR achievement was efficiently predicted by the gene expression patterns, with an overall accuracy exceeding 90%. Finally, a negative predictive value of 100% was validated in an independent series, thus representing the first molecular predictor for clinical response to a specific combination drug treatment for AML