Effects of computing parameters and measurement locations on the estimation of 3D NPS in non-stationary MDCT images.

The goal of this study was to investigate the impact of computing parameters and the location of volumes of interest (VOI) on the calculation of 3D noise power spectrum (NPS) in order to determine an optimal set of computing parameters and propose a robust method for evaluating the noise properties of imaging systems. Noise stationarity in noise volumes acquired with a water phantom on a 128-MDCT and a 320-MDCT scanner were analyzed in the spatial domain in order to define locally stationary VOIs. The influence of the computing parameters in the 3D NPS measurement: the sampling distances bx,y,z and the VOI lengths Lx,y,z, the number of VOIs NVOI and the structured noise were investigated to minimize measurement errors. The effect of the VOI locations on the NPS was also investigated. Results showed that the noise (standard deviation) varies more in the r-direction (phantom radius) than z-direction plane. A 25 × 25 × 40 mm(3) VOI associated with DFOV = 200 mm (Lx,y,z = 64, bx,y = 0.391 mm with 512 × 512 matrix) and a first-order detrending method to reduce structured noise led to an accurate NPS estimation. NPS estimated from off centered small VOIs had a directional dependency contrary to NPS obtained from large VOIs located in the center of the volume or from small VOIs located on a concentric circle. This showed that the VOI size and location play a major role in the determination of NPS when images are not stationary. This study emphasizes the need for consistent measurement methods to assess and compare image quality in CT.

Estimating parameters for generalized mass action models using constraint propagation.

As modern molecular biology moves towards the analysis of biological systems as opposed to their individual components, the need for appropriate mathematical and computational techniques for understanding the dynamics and structure of such systems is becoming more pressing. For example, the modeling of biochemical systems using ordinary differential equations (ODEs) based on high-throughput, time-dense profiles is becoming more common-place, which is necessitating the development of improved techniques to estimate model parameters from such data. Due to the high dimensionality of this estimation problem, straight-forward optimization strategies rarely produce correct parameter values, and hence current methods tend to utilize genetic/evolutionary algorithms to perform non-linear parameter fitting. Here, we describe a completely deterministic approach, which is based on interval analysis. This allows us to examine entire sets of parameters, and thus to exhaust the global search within a finite number of steps. In particular, we show how our method may be applied to a generic class of ODEs used for modeling biochemical systems called Generalized Mass Action Models (GMAs). In addition, we show that for GMAs our method is amenable to the technique in interval arithmetic called constraint propagation, which allows great improvement of its efficiency. To illustrate the applicability of our method we apply it to some networks of biochemical reactions appearing in the literature, showing in particular that, in addition to estimating system parameters in the absence of noise, our method may also be used to recover the topology of these networks.

The kinetic parameters and energy cost of the Hsp70 chaperone as a polypeptide unfoldase.

Hsp70-Hsp40-NEF and possibly Hsp100 are the only known molecular chaperones that can use the energy of ATP to convert stably pre-aggregated polypeptides into natively refolded proteins. However, the kinetic parameters and ATP costs have remained elusive because refolding reactions have only been successful with a molar excess of chaperones over their polypeptide substrates. Here we describe a stable, misfolded luciferase species that can be efficiently renatured by substoichiometric amounts of bacterial Hsp70-Hsp40-NEF. The reactivation rates increased with substrate concentration and followed saturation kinetics, thus allowing the determination of apparent V(max)' and K(m)' values for a chaperone-mediated renaturation reaction for the first time. Under the in vitro conditions used, one Hsp70 molecule consumed five ATPs to effectively unfold a single misfolded protein into an intermediate that, upon chaperone dissociation, spontaneously refolded to the native state, a process with an ATP cost a thousand times lower than expected for protein degradation and resynthesis.

Recurrent TET2 mutations in peripheral T-cell lymphomas correlate with TFH-like features and adverse clinical parameters.

Inactivating mutations of the Ten-Eleven Translocation 2 (TET2) gene were first identified in myeloid malignancies and more recently in peripheral T-cell lymphomas (PTCLs). In the present study, we investigated the presence of TET2 coding sequence mutations and their clinical relevance in a large cohort of 190 PTCL patients. TET2 mutations were identified in 40 of 86 (47%) cases of angioimmunoblastic T-cell lymphoma (AITL) and in 22 of 58 (38%) cases of peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS), but were absent in all other PTCL entities, with the exception of 2 of 10 cases of enteropathy-associated T-cell lymphoma. Among PTCL-NOS, a heterogeneous group of lymphoma-comprising cases likely to derive from Th follicular (T(FH)) cells similarly to AITL, TET2 mutations were more frequent when PTCL-NOS expressed T(FH) markers and/or had features reminiscent of AITL (58% vs 24%, P = .01). In the AITL and PTCL-NOS subgroups, TET2 mutations were associated with advanced-stage disease, thrombocytopenia, high International Prognostic Index scores, and a shorter progression-free survival.

Hes1 is a critical but context-dependent mediator of canonical Notch signaling in lymphocyte development and transformation.

Although canonical Notch signaling regulates multiple hematopoietic lineage decisions including T cell and marginal zone B cell fate specification, the downstream molecular mediators of Notch function are largely unknown. We showed here that conditional inactivation of Hes1, a well-characterized Notch target gene, in adult murine bone marrow (BM) cells severely impaired T cell development without affecting other Notch-dependent hematopoietic lineages such as marginal zone B cells. Competitive mixed BM chimeras, intrathymic transfer experiments, and in vitro culture of BM progenitors on Delta-like-expressing stromal cells further demonstrated that Hes1 is required for T cell lineage commitment, but dispensable for Notch-dependent thymocyte maturation through and beyond the beta selection checkpoint. Furthermore, our data strongly suggest that Hes1 is essential for the development and maintenance of Notch-induced T cell acute lymphoblastic leukemia. Collectively, our studies identify Hes1 as a critical but context-dependent mediator of canonical Notch signaling in the hematopoietic system.

Malignancy transformation of chronic osteomyelitis: description of 6 cases of Marjolin's ulcers

Marjolin's ulcer describes any malignant transformation of a chronic inflammatory lesion. In the majority of cases, a squamous cell carcinoma is diagnosed. Malignant transformation occurs usually after a long period of latency of chronic infection; it takes approximately 35 years on average. There are no typical clinical presentations, but several indirect signs may suggest the malignant transformation, such as increased or changed discharge, pathologic fracture, a slow-growing exophytic mass, or other suggestive signs of malignant transformation, which should prompt to biopsy for histological exam. The diagnosis of chronic osteomyelitis should not prevent to search for carcinoma. We present six patients with chronic osteomyelitis that developed well-differentiated squamous cell carcinoma. All patients were older than 50 years (mean 60 years, range 52-77 years). Five Marjolin's ulcers were located on the lower limb and one on the arm. The average time of the chronic discharging osteomyelitis before diagnosis of carcinoma ranged between 12 and 40 years. All patients were treated by amputation of the affected limb. None had metastasis, and one patient developed local recurrence and received palliative treatment. Our study emphasizes that Marjolin's ulcer should be considered as a rare but significant long-term complication of chronic osteomyelitis. The finding of microorganisms should not prevent from further diagnostic procedures by histopathological examination so that the correct surgical treatment can be performed.

Chiasmatic infiltration secondary to late malignant transformation of retinoma.

PURPOSE: To report the lethal course of malignant transformation of retinoma in an adult. METHODS: Case report. A 40-year-old patient presented with retinoma in his right eye and retinoblastoma in his left eye. Enucleation was recommended but refused and the patient received whole eye radiotherapy elsewhere. Five years later he presented again, with temporal hemianopsia of the left eye secondary to chiasmatic invasion. RESULTS: Diagnosis of retinoblastoma infiltration was confirmed by stereotactic biopsy of the chiasmatic lesion. Treatment with intravenous and intrathecal chemotherapy led to partial remission, and was followed by stereotactic irradiation of the chiasmatic mass and right optic nerve. The left eye was enucleated. Death occurred one year later due to cerebrospinal fluid metastases. CONCLUSION: Extraocular extension of retinoblastoma diagnosed in adulthood has never, to our knowledge, been reported. This case stresses the importance of lifelong retinoma monitoring and the necessity for radical treatment in the event of malignant transformation.

Is blood still thicker than water? A life-course perspective on the transformation of family and friends' roles in personal networks

This thesis addresses the issue of the moving boundaries between family and friends' roles in personal networks, adopting a life-course perspective and using Switzerland as a case study. In a period of major changes in personal life happening in contemporary Western societies, understanding the organization of personal networks intertwined with the unfolding of individual life courses is of prime importance in facing new challenges with regard to social integration. The data stem from a representative national survey carried out in 2011 named Family tiMes, including 803 individuals born either in 1950-1955 or in 1970-1975. An innovative research design was adopted, combing cross-sectional ego-centered network data and retrospective longitudinal life-course data. The results show continuing boundaries between family and friends' roles and that family keeps a prominent role in personal networks despite the notable importance of friendship ties. One relationship stands out above all, that with the partner, followed quite a few steps behind by those with children. Regarding life courses, de-standardization tendencies were found in family formation and also a persistent gendering of occupational trajectories. Two kinds of life trajectories are particularly intertwined with personal networks, co-residence and partnership trajectories, both related to the unfolding of family life. In particular, transition to parenthood functions as a turning point in individuals' lives, deeply transforming their sociability. Finally, a twofold pluralization process was identified, affecting simultaneously the organization of personal networks and the unfolding of individual life courses. This thesis contributes to the literature on the sociology of family and personal life, and to fruitful interlinkage between the network approach and the life-course perspective.