Endothelial cells as key determinants of the tumor microenvironment: interaction with tumor cells, extracellular matrix and immune killer cells.

Besides tumor cells, the tumor microenvironment harbors a variety of host-derived cells, such as endothelial cells, fibroblasts, innate and adaptive immune cells. It is a complex and highly dynamic environment, providing very important cues to tumor development and progression. Tumor-associated endothelial cells play a key role in this process. On the one hand, they form tumor-associated (angiogenic) vessels through sprouting from locally preexisting vessels or recruitment of bone marrow-derived endothelial progenitor cells, to provide nutritional support to the growing tumor. On the other hand, they are the interface between circulating blood cells, tumor cells and the extracellular matrix, thereby playing a central role in controlling leukocyte recruitment, tumor cell behavior and metastasis formation. Hypoxia is a critical parameter modulating the tumor microenvironment and endothelial/tumor cell interactions. Under hypoxic stress, tumor cells produce factors that promote tumor angiogenesis, tumor cell motility and metastasis. Among these factors, VEGF, a main angiogenesis modulator, can also play a critical role in the control of immune tolerance. This review discusses some aspects of the role of endothelial cells within tumor microenvironment and emphasizes their interaction with tumor cells, the extracellular matrix and with immune killer cells. We will also address the role played by circulating endothelial progenitor cells and illustrate their features and mechanism of recruitment to the tumor microenvironment and their role in tumor angiogenesis.

Sea-level changes and ammonite faunal turnover during the Lias/Dogger transition in the western Tethys

The aim of this paper was to investigate the possible connections between ammonite faunal turnover and the eustatic events recorded in Tethyan sequences during the middle Toarcian/early Bajocian time interval. For this we have analysed the biostratigraphic ranges, at the subzone level, of approximately 600 ammonite species belonging to 160 genera from several selected sections of the western Tethys (Mediterranean and Submediterranean provinces). The analysis of taxon ranges enabled us to plot curves for ammonite faunal turnovers, inter-subzonal distance, and diversity. Comparing the mentioned curves with Tethyan sequences [Hardenbol et al., 19981, we find that sea-level changes correlate well with origination and extinction events and faunal diversity. Most of the faunal turnovers correlate with stratigraphic events. Extinction events with their corresponding decrease in diversity correlate with regressive intervals and with major or minor sequence boundaries. Origination events and their corresponding increase in diversity were clearly connected with transgressions in Tethyan sequences. In several cases, the major sequence boundary and the subsequent transgressive phase correlate with major ammonite faunal turnover, whereas minor or medium sequence boundaries generally gave rise to minor or medium turnovers.

Different transcriptional control of metabolism and extracellular matrix in visceral and subcutaneous fat of obese and rimonabant treated mice.

BACKGROUND: The visceral (VAT) and subcutaneous (SCAT) adipose tissues play different roles in physiology and obesity. The molecular mechanisms underlying their expansion in obesity and following body weight reduction are poorly defined. METHODOLOGY: C57Bl/6 mice fed a high fat diet (HFD) for 6 months developed low, medium, or high body weight as compared to normal chow fed mice. Mice from each groups were then treated with the cannabinoid receptor 1 antagonist rimonabant or vehicle for 24 days to normalize their body weight. Transcriptomic data for visceral and subcutaneous adipose tissues from each group of mice were obtained and analyzed to identify: i) genes regulated by HFD irrespective of body weight, ii) genes whose expression correlated with body weight, iii) the biological processes activated in each tissue using gene set enrichment analysis (GSEA), iv) the transcriptional programs affected by rimonabant. PRINCIPAL FINDINGS: In VAT, "metabolic" genes encoding enzymes for lipid and steroid biosynthesis and glucose catabolism were down-regulated irrespective of body weight whereas "structure" genes controlling cell architecture and tissue remodeling had expression levels correlated with body weight. In SCAT, the identified "metabolic" and "structure" genes were mostly different from those identified in VAT and were regulated irrespective of body weight. GSEA indicated active adipogenesis in both tissues but a more prominent involvement of tissue stroma in VAT than in SCAT. Rimonabant treatment normalized most gene expression but further reduced oxidative phosphorylation gene expression in SCAT but not in VAT. CONCLUSION: VAT and SCAT show strikingly different gene expression programs in response to high fat diet and rimonabant treatment. Our results may lead to identification of therapeutic targets acting on specific fat depots to control obesity.

On the convergence of EM-like algorithms for image segmentation using Markov random fields.

Inference of Markov random field images segmentation models is usually performed using iterative methods which adapt the well-known expectation-maximization (EM) algorithm for independent mixture models. However, some of these adaptations are ad hoc and may turn out numerically unstable. In this paper, we review three EM-like variants for Markov random field segmentation and compare their convergence properties both at the theoretical and practical levels. We specifically advocate a numerical scheme involving asynchronous voxel updating, for which general convergence results can be established. Our experiments on brain tissue classification in magnetic resonance images provide evidence that this algorithm may achieve significantly faster convergence than its competitors while yielding at least as good segmentation results.

Molecular characterization of a human matrix attachment region epigenetic regulator.

Matrix attachment regions (MAR) generally act as epigenetic regulatory sequences that increase gene expression, and they were proposed to partition chromosomes into loop-forming domains. However, their molecular mode of action remains poorly understood. Here, we assessed the possible contribution of the AT-rich core and adjacent transcription factor binding motifs to the transcription augmenting and anti-silencing effects of human MAR 1-68. Either flanking sequences together with the AT-rich core were required to obtain the full MAR effects. Shortened MAR derivatives retaining full MAR activity were constructed from combinations of the AT-rich sequence and multimerized transcription factor binding motifs, implying that both transcription factors and the AT-rich microsatellite sequence are required to mediate the MAR effect. Genomic analysis indicated that MAR AT-rich cores may be depleted of histones and enriched in RNA polymerase II, providing a molecular interpretation of their chromatin domain insulator and transcriptional augmentation activities.

Smooth transition or permanent exit? Evidence on job prospects of displaced industrial workers

This article examines the job prospects of displaced industrial workers in Switzerland. Based on a survey of 1,203 workers who were dismissed after their manufacturing plants closed down, we analyse the determinants of re-employment, the sector of re-employment and the change in wages. Two years after displacement, a majority of workers were back in employment: 69% were re-employed, 17% un-employed and 11% retired. Amongst re-employed workers, two thirds found a job in manufacturing and one third in services. Contrary to a common belief, low-end services are not the collecting vessel of redundant industrial workers. Displaced workers aged 55 and older seem particularly vulnerable after a plant closes down: over 30% were long-term unemployed, and those older workers who found a new job suffered disproportionate wage losses. Advanced age-and not low education-appears as the primary handicap after mass redundancy.

A performance lower bound for quadratic timing recovery accounting for the symbol transition density

The symbol transition density in a digitally modulated signal affects the performance of practical synchronization schemes designed for timing recovery. This paper focuses on the derivation of simple performance limits for the estimation of the time delay of a noisy linearly modulated signal in the presence of various degrees of symbol correlation produced by the varioustransition densities in the symbol streams. The paper develops high- and low-signal-to-noise ratio (SNR) approximations of the so-called (Gaussian) unconditional Cramér–Rao bound (UCRB),as well as general expressions that are applicable in all ranges of SNR. The derived bounds are valid only for the class of quadratic, non-data-aided (NDA) timing recovery schemes. To illustrate the validity of the derived bounds, they are compared with the actual performance achieved by some well-known quadratic NDA timing recovery schemes. The impact of the symbol transitiondensity on the classical threshold effect present in NDA timing recovery schemes is also analyzed. Previous work on performancebounds for timing recovery from various authors is generalized and unified in this contribution.

On the inclusion of channel's time dependence in a hidden Markov model for blind channel estimation

In this paper, the theory of hidden Markov models (HMM) isapplied to the problem of blind (without training sequences) channel estimationand data detection. Within a HMM framework, the Baum–Welch(BW) identification algorithm is frequently used to find out maximum-likelihood (ML) estimates of the corresponding model. However, such a procedureassumes the model (i.e., the channel response) to be static throughoutthe observation sequence. By means of introducing a parametric model fortime-varying channel responses, a version of the algorithm, which is moreappropriate for mobile channels [time-dependent Baum-Welch (TDBW)] isderived. Aiming to compare algorithm behavior, a set of computer simulationsfor a GSM scenario is provided. Results indicate that, in comparisonto other Baum–Welch (BW) versions of the algorithm, the TDBW approachattains a remarkable enhancement in performance. For that purpose, onlya moderate increase in computational complexity is needed.

Blind channel estimation and data detection using hidden Markov models theory

In this correspondence, we propose applying the hiddenMarkov models (HMM) theory to the problem of blind channel estimationand data detection. The Baum–Welch (BW) algorithm, which is able toestimate all the parameters of the model, is enriched by introducingsome linear constraints emerging from a linear FIR hypothesis on thechannel. Additionally, a version of the algorithm that is suitable for timevaryingchannels is also presented. Performance is analyzed in a GSMenvironment using standard test channels and is found to be close to thatobtained with a nonblind receiver.

Family interactions in IVF families: change over the transition to parenthood

Objective: This article presents a study of the change over time in the family interactions of couples who conceived through in-vitro fertilisation (IVF). Background: Observational methods are rarely used to study family interactions in families who used assisted reproductive techniques, but these methods are crucial for taking account of the communication that occurs in interactions with infants. Methods: Thirty-one couples expecting their first child were seen during the fifth month of pregnancy and when the child was nine months old. Family interactions were recorded in pre- and postnatal versions of the Lausanne Trilogue Play situation. Measures of marital satisfaction and parent-to-foetus/baby attachment or 'bonding' were also used to assess family relational dynamics. Results: Results showed that family alliance, marital satisfaction and parental attachment scores in the IVF sample were all similar to or higher than those in the reference sample during pregnancy. However, at nine months postnatally, the family alliance scores were lower. While marital satisfaction decreased over the period and parent-baby attachment increased, the family alliance scores were unstable, as no association was observed between the pre- and postnatal scores. In addition, neither prenatal marital satisfaction nor parent-foetus attachment predicted the postnatal family alliance. Conclusion: The change in the family alliance over the transition to parenthood appears to be specific to our IVF sample. Given that postnatal family functioning could not be predicted by prenatal family functioning, our observational data underline the importance of offering postnatal support to these families.

Organic geochemistry across the Permian-Triassic transition at the Idrijca Valley, Western Slovenia

Bulk and molecular stable C isotopic compositions and biomarker distributions provide evidence for a diverse community of algal and bacterial organisms in the sedimentary organic matter of a carbonate section throughout the Permian-Triassic (P/Tr) transition at the Idrijca Valley, Western Slovenia. The input of algae and bacteria in all the Upper Permian and Lower Scythian samples is represented by the predominance of C-15-C-22 n-alkanes, odd C-number alkylcyclohexanes, C-27 steranes and substantial contents Of C-21-C-30 acyclic isoprenoids. The occurrence of odd long-chain n-alkanes (C-22-C-30) and C29 steranes in all the samples indicate a contribution of continental material. The decrease of C-org and C-carb contents, increase of Rock-Eval oxygen indices, and C-13-enrichment of the kerogen suggest a decrease in anoxia of the uppermost Permian bottom water. The predominance of odd C-number alkylcycloalkanes, C-27 steranes, and C-17 n-alkanes with delta(13)C values similar to-30parts per thousand, and C-13-enrichment of the kerogens in the lowermost Scythian samples are evidence of greater algal productivity. This increased productivity was probably sustained by a high nutrient availability and changes of dissolved CO2 speciation associated to the earliest Triassic transgression. A decrease Of Corg content in the uppermost Scythian samples, associated to a C-13-depletetion in the carbonates (up to 4parts per thousand) and individual n-alkanes (up to 3.4parts per thousand) compared to the Upper Permian samples, indicate lowering of the primary productivity (algae, cyanobacteria) and/or higher degradation of the organic matter. (C) 2003 Elsevier Ltd. All rights reserved.

Aortic biological valve prosthesis in patients younger than 65 years of age: transition to a flexible age limit?

OBJECTIVES Guidelines proposed bioprosthesis implantation for aortic valve disease if the patients were at least 65 years old at the time of surgery, with a trend towards even younger patients in recent years. Considering the adverse effects of lifetime anticoagulation, new biological valves (less prone to degeneration) and new technologies may lead patients and surgeons to different choices. Therefore, it is interesting to analyse the results of aortic bioprosthetic valve replacement in patients aged <65 years at the time of surgery. METHODS From January 2000 to December 2010, 84 patients aged <65 years at the time of surgery had undergone an aortic bio-prosthetic valve replacement. A mid-term follow-up [(FU) mean FU time: 54.4 ± 39.2 months] was done in August 2011 in all patients (FU completeness: 100%). Results were compared with patients who had a mechanical prosthetic aortic valve replacement during the same period. RESULTS The reoperation rate for structural valve degeneration (SVD) of bioprostheses was 6% and occurred exclusively among patients <56 years. Contraindications for anticoagulation determined the choice of a bioprosthesis among 83% of these patients. The personal preference to avoid anticoagulation was the leading cause in 68% of the older patients (56-65 years). Neurological complications occurred more frequently in the mechanical control group. CONCLUSIONS Reoperations for SVD after bioprosthesis implantation occurred exclusively among younger patients (<56 years), not suitable for systemic anticoagulation. Previous studies, together with our experience, are in favour of an age limit between 56 and 60 years, taking into consideration alternative transcatheter approaches to SVD treatment.

Cenomanian-Turonian transition in a shallow water sequence of the Sinai, Egypt

Environmental and depositional changes across the Late Cenomanian oceanic anoxic event (OAE2) in the Sinai, Egypt, are examined based on biostratigraphy, mineralogy, delta(13)C values and phosphorus analyses. Comparison with the Pueblo, Colorado, stratotype section reveals the Whadi El Ghaib section as stratigraphically complete across the late Cenomanian-early Turonian. Foraminifera are dominated by high-stress planktic and benthic assemblages characterized by low diversity, low-oxygen and low-salinity tolerant species, which mark shallow-water oceanic dysoxic conditions during OAE2. Oyster biostromes suggest deposition occurred in less than 50 m depths in low-oxygen, brackish, and nutrient-rich waters. Their demise prior to the peak delta(13)C excursion is likely due to a rising sea-level. Characteristic OAE2 anoxic conditions reached this coastal region only at the end of the delta(13)C plateau in deeper waters near the end of the Cenomanian. Increased phosphorus accumulations before and after the delta(13)C excursion suggest higher oxic conditions and increased detrital input. Bulk-rock and clay mineralogy indicate humid climate conditions, increased continental runoff and a rising sea up to the first delta(13)C peak. Above this interval, a dryer and seasonally well-contrasted climate with intermittently dry conditions prevailed. These results reveal the globally synchronous delta(13)C shift, but delayed effects of OAE2 dependent on water depth.

Challenge of transition in the socio-professional insertion of youngsters with neurodisabilities.

Objective: To evaluate the activities of patients with neurodisabilities and assess their insertion problems in the professional world. Methods: It is based on medical records of 267 patients (224 with neurodevelopmental diseases and 43 with neuromuscular diseases), aged 16-25 years, followed in the transition clinic of young adults in the neurorehabilitation services of a tertiary center. Results: Nearly half of them (46.8%) were in a protected environment, 37.08% studied and only 3.4% worked. Their studies are much longer and they are less in university than Swiss people of same age. The competitiveness criteria are no mental retardation and to be completely independent. Finally, 29.2% reported work problems, the foremost being the lack of adaptation in the workplace. Conclusion: These results highlight the need to increase the integration of young adults with neuromotor disorders in the labor market.