Relaxation of the mouse pubic symphysis during late pregnancy is not accompanied by the influx of granulocytes

In some animals, such as mice and guinea pigs, a hormonally controlled mechanism increases the flexibility of the pubic symphysis and enhances the cervical remodeling necessary for safe delivery. Cervical ripening during pregnancy is associated with a paradoxical influx of leukocytes. However, the changes in cell metabolism during relaxation of the mouse pubic symphysis for delivery have not been extensively studied. In this work, we used light microscopy and transmission and scanning electron microcopy, as well as immunohistochemistry and Western blotting for MMP-8, to investigate the involvement of granulocytes or resident stromal cells in the relaxation of the virgin pubic symphysis during late pregnancy (days 18 and 19, before delivery) in vivo and in explanted joints. MMP-8 was studied because this collagenase is a hallmark for cervical ripening associated with the influx of granulocytes during late pregnancy. Extensive dissolution and disorganization of the extracellular matrix was seen around fibroblastic-like cells in late pregnancy. In contrast to the cervix (positive control), morphological and immunohistochemical analyses revealed that there was no characteristic cellular inflammatory response in the interpubic tissue. Staining for MMP-8 was observed in chondroid and fibroblastic-like cells of virgin and relaxed interpubic ligament, respectively. However, no granulocytes were seen during the extensive remodeling of the pubic joint in late pregnancy. These results indicate that constitutive stromal cells may have an important role in tissue relaxation during remodeling of the pubic symphysis in pregnancy.     

On the stochastic timed Pétri nets model and its application to the DQDB protocol

The goal of this paper is twofold : at first, to present the stochastic timed Pétri nets model by emphasizing its ability to express the main characteristics of real time distributed systems (parallelism, synchronization by message exchange, time attributes and in particular time constraints) and to allow both qualitative and quantitative analysis (concept of randomized states graph); second, to show a modeling methodology based on this model that allows a rigorous modeling of theDqdb protocol (Qa access, bwb mechanism role,Pa access influence). A new contribution to theQa mechanism has been done (1).     

Real-time digital control of optical interferometers by the mechanical-modulation technique

We discuss the application of digital systems to the automatic control of dual-wave optical interferometers. We show that, if the mechanical-modulation technique is used for error-signal extraction, digital techniques can be used both for error-signal extraction and for control-signal generation. Therefore, apart from two front/end amplifiers that are necessary to match the dynamics of the detectors and actuators to the dynamics of the analog-to-digital converters and digital-to-analog converters, no other analog devices are required. In particular, the mechanical-modulation technique requires the synchronous demodulation of the photodiode output signal. Hence we need to implement a digital lock-in amplifier whose algorithm is described here. Finally, we describe one of the possible applications of this digital control procedure, such as the control of a classic Mach-Zehnder interferometer in air.     

Sorafenib delivery nanoplatform based on superparamagnetic iron oxide nanoparticles magnetically targets hepatocellular carcinoma

Currently,sorafenib is the only systemic therapy capable of increasing overall survival of hepatocellular carcinoma patients.Unfortunately,its side effects,particularly its overall toxicity,limit the therapeutic response that can be achieved.Superparamagnetic iron oxide nanoparticles (SPIONs) are very attractive for drug delivery because they can be targeted to specific sites in the body through application of a magnetic field,thus improving intratumoral accumulation and reducing adverse effects.Here,nanoformulations based on polyethylene glycol modified phospholipid micelles,loaded with both SPIONs and sorafenib,were successfully prepared and thoroughly investigated by complementary techniques.This nanovector system provided effective drug delivery,had an average hydrodynamic diameter of about 125 nm,had good stability in aqueous medium,and allowed controlled drug loading.Magnetic analysis allowed accurate determination of the amount of SPIONs embedded in each micelle.An in vitro system was designed to test whether the SPION micelles can be efficiently held using a magnetic field under typical flow conditions found in the human liver.Human hepatocellular carcinoma (HepG2) cells were selected as an in vitro system to evaluate tumor cell targeting efficacy of the superparamagnetic micelles loaded with sorafenib.These experiments demonstrated that this delivery platform is able to enhance sorafenib's antitumor effectiveness by magnetic targeting.The magnetic nanovectors described here represent promising candidates for targeting specific hepatic tumor sites,where selective release of sorafenib can improve its efficacy and safety profile.     

Minimum Setup Minimum Aberration Two‐level Split‐plot Type Designs for Physical Prototype Testing

Although new technologies allow for less effort in prototyping, physical testing still remains an important step in the product development cycle. Well‐planned experiments are useful to guide the decision‐making process. During the design of an experiment, one of the challenges is to balance limited resources and system constraints to obtain useful information. It is common that prototypes are composed of several parts, with some parts more difficult to assemble than others. And, usually, there is only one piece available of each part type and a large number of different setups. Under these conditions, designs with randomization restrictions become attractive approaches. Considering this scenario, a new and additional criterion, minimum setup, to construct split‐plot type designs is presented. Designs with the minimum number of setups of the more difficult parts, which are especially useful for screening purposes in physical prototype testing, are discussed. The use of the proposed criterion combined with minimum aberration for selecting a regular design is shown through a real application in testing car prototypes. As a tool to practitioners, catalogs of selected 32‐run minimum setup minimum aberration split‐split‐plot and split‐split‐split‐plot designs are presented. More complete catalogs are available as Supporting information. Copyright © 2015 John Wiley & Sons, Ltd.     

Recommendation of RILEM Technical Committee 250-CSM: Test method for Textile Reinforced Mortar to substrate bond characterization

Textile Reinforced Mortar (TRM), also known as Fabric Reinforced Mortar or Fabric Reinforced Cementitious Matrix, composites are an emerging technology for the external repair and strengthening of existing structures. For most applications, the effectiveness of the TRM reinforcement relies on its bond performance. This recommendation identifies the best practice to characterize the bond behaviour of TRM. A shear bond test method is proposed to determine the peak axial stress (associated with the maximum load that can be transferred from the structural member to the externally bonded TRM reinforcement), the stress–slip relationship and the failure mode that controls the TRM-to-substrate load transfer capacity. Guidelines on specimen manufacturing, experimental setup, test execution, and determination of test results are provided.     

Comparison between TRH-stimulated TSH and basal TSH measurement by a commercial immunoradiometric assay in the management of thyroid disease

In order to assess the current diagnostic role of the TRH test following the introduction of more sensitive "second generation" TSH assays, we studied a series of 259 outpatients, 237 women and 22 men, mean age 44.7 years (range 12-82), 91 of whom (35%) with untreated simple goiter, 133 (51%) with simple nodular goiter on steady state I-thyroxine treatment, 18 (7%) with overt or subclinical hyperthyroidism and 17 (7%) with overt or subclinical hypothyroidism, compared to a control group of 26 euthyroid healthy subjects. Serum TSH was measured by a commercial immunoradiometric assay (clinical sensitivity 0.1 microU/ml). TSH response to TRH was evaluated 30 minutes after giving 200 micrograms TRH i.v. bolus, the results being analyzed both as absolute increase (delta-TSH=stimulated TSH minus basal TSH) and as relative increase (R-TSH stimulated TSH/basal TSH). Using cut-off values of 0.3-3.2 microU/ml, basal TSH measurement was able to detect hypothyroidism (specificity = 100%) and to exclude hyperthyroidism (sensivity = 96.9%), but failed to accurately prove hyperthyroidism (specificity = 93.4%) and, above all, to exclude hypothyroidism (sensitivity = 35.3%) in our ambulatory patients. The delta-TSH values showed a basal TSH dependent linear increase (r = + 0.87, p < 0.001) both including only patients (n = 139) with basal TSH level in the euthyroidism range and including all patients (n = 223) having TSH responsive to TRH. All the patients with detectable basal TSH level displayed detectable TSH response to TRH, as did 19 (= 23.5%) of 81 patients with undetectable (< 0.1 microU/ml) basal value. In particular: a) for subnormal but detectable basal TSH ranging between 0.1 and 0.2 microU/ml, TSH was always hyporesponsive (delta-TSH < or = 2.5 microU/ml), while between 0.2 and 0.3 microU/ml TSH was hyporesponsive in 72.2% and normoresponsive (delta-TSH > 2.5 and < or = 11.9 microU/ml) in the remaining 27.8%; b) for basal TSH values within the normal range (0.3-3.2 microU/ml). TSH was hyporesponsive in 13.7%, normoresponsive in 74.8% and hyperresponsive in 11.5%; c) for high basal TSH values TSH was always hyperresponsive. The analysis of R TSH showed relatively constant values in the range of euthyroidism and hypothyroidism (m +/- SD: 7.4 +/- 2.3 and 7.7 +/- 3.1, respectively), and a marked differentiation of hyperthyroid patients whose R-TSH values were significantly lower (4.2 +/- 3.4) but had a wide individual variability. Linear regression analysis of basal or stimulated TSH and circulating thyroid hormones showed a close negative relationship, being highly significant between delta-TSH and T4 (r = 0.57, p < 0.001) and delta-TSH and FT4 (r = 0.46, p < 0.001). In conclusion, after the introduction of current second generation TSH immunoradiometric assay, the diagnostic role of the TRH test is greatly limited but not to be excluded: it can provide additional information to that obtained with simple basal TSH measurement in the diagnosis of subclinical hypothyroidism and in the precise evaluation of the degree of TSH suppression in patients with a subnormal basal TSH, either for endogenous thyrotoxicosis or I.-thyroxine treatment.     

Formalizing process-based risk with Value-Focused Process Engineering

Following calls to advance the integration of risk and business process modeling paradigms, this paper formalizes the process of incorporating risk into business process models through the principles of Value-Focused Process Engineering (VFPE). In doing so, the paper aims to extend the existing VFPE modeling notation to reflect a set of necessary constructs required to adequately represent risk in goal-oriented business-process models. The extended set of constructs is proposed to support a formal systems view of process-based risk. Process-based risk is formalized on the one hand, as a product of complex interactions between activity-based elements, and on the other hand, as a natural component of the value creation mechanism of an elementary function or a complex process. The proposed risk-aware VFPE formalism also formulates rules for decomposing risk in process models according to the organizational values, thereby enabling better risk visibility, reducing process complexity, and ensuring continuity of business processes.