Creating and Justifying Research and Development Value: Scope,Scale, Skill and Social Networking of R&D

In this paper we describe a framework for analysing the creation and justification of Research & Development. The 4S framework is developed for analysing the scope, scale, skills and social network aspects of Research & Development value. The framework is based on social system theory, a process contingency model, and recent Research & Development metrics. We present a first empirical assessment based on a workshop using the 4S framework for leveraging Research & Development. Results that assist in the assessment of value creation utilising R & D within networks are very relevant in high tech industries. The multi–dimensional process approach of this framework seems promising for understanding and managing R&D value creation, but needs further operationalisation. Case studies are described and a Dutch network on leveraging R&D has been initiated.     

Familial idiopathic intracranial hypertension with spinal and radicular pain

OBJECTIVE: To describe a mother and her 2 sons affected by idiopathic intracranial hypertension (IIH), associated in the sons with root irritation symptom. Unlike the other 4 families reported previously, obesity was not present in our patients. DESIGN: Case reports. SETTING: Department of pediatrics in a university school of Medicine, Naples, Italy. PATIENTS: A mother (aged 36 years) and her 2 sons (aged 14 and 9 years) developed IIH at different times. Neuroimaging showed an empty sella in the mother, while IIH was associated with spinal and radicular pain in her 2 sons. The mother and the younger son developed permanent visual loss. CONCLUSIONS: Ophthalmologic follow-up in our patients indicates that IIH is a chronic disease. Surgical treatment should be considered an option.     

Surveillance after colorectal cancer surgery

Early diagnosis of local and distant recurrences of colorectal cancer remains difficult and there is no agreement on the effectiveness of follow-up in these patients. The aim of this study is to assess the value of our method of follow-up. We consider 239 patients with colorectal cancer and at least 2 years follow-up following radical resection. A local recurrence appeared in 26 patients (10.9%), a distant metastasis in 41 (17.1%), while in seven (2.9%) local and distant recurrences appeared simultaneously. Local recurrence was detected because of an increase in carcinoembryonic antigen (CEA) level in 15 patients (57.7%), during a scheduled endoscopy in four (15.4%) and because of symptoms in seven (26.9%). In seven patients (26.9%) a radical resection was possible. Distant metastases were detected by CEA levels in 20 patients (48.8%), by ultrasonography (U.S.) in 12 (29.3%) and by chest X-ray in five (12.2%). In 13 of 26 patients with liver metastases a resection was performed. This study shows that few patients benefit from follow-up and only CEA levels and liver U.S. performed intensively between 15 and 36 months after surgery are useful in early detection of recurrences. A modification of the follow-up to the single patient, according to the stage, location and grading of cancer, could improve the results, so lowering the costs of this expensive practice.     

Direct monitoring of the calcium concentration in the sarcoplasmic and endoplasmic reticulum of skeletal muscle myotubes

Direct monitoring of the free Ca2+ concentration in the sarcoplasmic reticulum (SR) was carried out in rat skeletal myotubes transfected with a specifically targeted aequorin chimera (srAEQ). Myotubes were also transfected with a chimeric aequorin (erAEQ) that we have demonstrated previously is retained in the endoplasmic reticulum (ER). Immunolocalization analysis showed that although both recombinant proteins are distributed in an endomembrane network identifiable with immature SR, the erAEQ protein was retained also in the perinuclear membrane. The difficulty of measuring [Ca2+] in 100-1000 microM range was overcome with the use of the synthetic coelenterazine analogue, coelenterazine n. We demonstrate that the steady state levels of [Ca2+] measured with srAEQ is around 300 microM, whereas that measured with erAEQ is significantly lower, i.e. around 200 microM. The effects of caffeine, high KCl, and nicotinic receptor stimulation, in the presence or absence of external calcium or after blockade of the Ca-ATPase, were investigated with both chimeras. The kinetics of [Ca2+] changes revealed by the erAEQ were similar, but not identical, neither quantitatively nor qualitatively, to those monitored with the srAEQ, indicating that at this stage of muscle development, differences exist between SR and ER in their mechanisms of Ca2+ handling. The functional implications of these findings are discussed.     

Efficacy of lonidamine combined with different DNA-damaging agents in the treatment of the MX-1 tumor xenograft

The a.c. conductivity of the proteins lysozyme and subtilisin, both in their active and inactive or inhibited forms were determined theoretically. For this, quantum mechanical calculations and a random walk theory were used. The conclusions are that these enzymatic proteins can easily transport electrons which is most probably important in their role as catalysators of biochemical reactions. The electron transport is sensitive to three-dimensional changes of the active sites of these enzymes which have more flexibility than the whole molecule. Therefore, the flexibility of the active sites of enzyme catalysts is not only important for the conformational fitting with the reactants, but also strongly influences the transport in biochemical reactions.     

Salvage chemotherapy with mitomycin, vindesine, and cisplatin (MiViP) in recurrent carcinoma of the cervix

We report two cases of metastatic non-functioning pancreatic endocrine tumour with very elevated plasma levels of alpha-fetoprotein. In these two cases, serial plasma levels of alpha-fetoprotein, initially normal, correlated well with hepatic tumour progression and were associated with fatal outcome. These results suggest that elevated plasma concentration of alpha-fetoprotein may be caused by metastatic pancreatic endocrine tumour and than alpha-fetoprotein serial measurement may be useful in prognostic evaluation.     

Hydrocarbon exploration risk evaluation through uncertainty and sensitivity analyses techniques

The evaluation of the exploration risk in the oil industry is a fundamental component of the decision process related to the exploratory phase. In this paper the two basic components of the exploratory risk: trap geometry and trapped hydrocarbon quantities (fluid), are compounded in a single coherent uncertainty and sensitivity approach. The results clarify that the model geometry influences each Petroleum System Modeling step and that the geometric uncertainty is correlated with the fluid uncertainty. The geometric uncertainty evaluation makes use of geostatistical techniques that produce a number of possible realizations of the trap geometry, all compatible with available data. The evaluation of the fluid uncertainty, through a Monte Carlo methodology, allows us to compute the possible quantities of oil and gas, generated in a basin and migrated from the hydrocarbon source location to each single trap. The final result is the probability distribution of oil and gas for each trap in the basin, together with other useful indicators like: the hydrocarbon filling probability map, the closure probability map, the drainage area probability map, the spilling paths probabilities, the trap-filling scenarios.     

The geometric nature of plasticity laws

This paper concerns the plasticity constitutive laws in small strain. In the thermodynamic approach developed here, the key concept is that of internal variables. The differential nature of plasticity law has been pointed out for a long time. If we unite the invariance condition of these laws in a state variable transformation, this involves, ultimately, that the natural mathematic frame of plasticity theory is Differential Geometry. The system state is defined as a point of a differentiable manifold. The state variable are the local coordinates of this point in a chart. The internal stresses are the components of a covariant vector of the cotangent bundle to internal state manifold and the elastic domain is a convex part of cotangent vector space. The plastic yield criteria such as von Mises condition define a Riemannian structure over the manifold. The metric element is identified with the internal dissipation element. Constitutive laws link the covariant derivatives of the thermodynamic stress with the state variable. Hardening modulus splits up in two parts, kinematic hardening and metric hardening. This last is defined by Christoffel connection coefficients. Applied to von Mises isotropic yield condition, the metric hardening is identified with isotropic hardening. The Baltov-Sawczuk model is also analysed. The use of appropriate polar coordinates simplifies significantly the computations. Generalization to a significant category of non-differentiable yield criteria, such as Tresca condition, is considered by introducting a metric tensor family. The adaptation of Drucker's postulate to the proposed model requires the introduction of parallel transport of the internal stress covector. Generally, this transport is different over distinctive paths joining two points. This fact expresses internal state manifold curvature. The Riemann-Christoffel tensor is computed for von Mises, Baltov-Sawczuk and Tresca models.     

Characterization of an ASIC for CPG sensors with grid-only depth of interaction sensing

A new version of the front-end application specific integrated circuit (ASIC) for co-planar-grid (CPG) sensors is presented. Compared to the first version, the ASIC is optimized for signal/noise performance, modified in peaking time, and it implements timing signals to measure the depth of interaction using the grids signals only. Experimental results using state-of the-art CPG sensors and different approaches for reducing the error due to electron trapping are reported. A new technique that makes use of the sum and difference of the grids signals is also presented.