Removal of MuRF1 Increases Muscle Mass in Nemaline Myopathy Models,but Does Not Provide Functional Benefits

Nemaline myopathy (NM) is characterized by skeletal muscle weakness and atrophy. No curative treatments exist for this debilitating disease. NM is caused by mutations in proteins involved in thin-filament function, turnover, and maintenance. Mutations in nebulin, encoded by NEB, are the most common cause. Skeletal muscle atrophy is tightly linked to upregulation of MuRF1, an E3 ligase, that targets proteins for proteasome degradation. Here, we report a large increase in MuRF1 protein levels in both patients with nebulin-based NM, also named NEM2, and in mouse models of the disease. We hypothesized that knocking out MuRF1 in animal models of NM with muscle atrophy would ameliorate the muscle deficits. To test this, we crossed MuRF1 KO mice with two NEM2 mouse models, one with the typical form and the other with the severe form. The crosses were viable, and muscles were studied in mice at 3 months of life. Ultrastructural examination of gastrocnemius muscle lacking MuRF1 and with severe NM revealed a small increase in vacuoles, but no significant change in the myofibrillar fractional area. MuRF1 deficiency led to increased weights of various muscle types in the NM models. However, this increase in muscle size was not associated with increased in vivo or in vitro force production. We conclude that knocking out MuRF1 in NEM2 mice increases muscle size, but does not improve muscle function.     

A Space-Time Meshless Method That Removes Numerical Oscillations When Solving PDEs with High Discontinuities

A space-time diffuse approximation method avoiding any secondary finite-difference time-stepping procedure, is presented to solve partial differential equations (PDEs) containing high discontinuities. This method is validated with a non-inner source heat equation. It is shown that its accuracy is improved when using a new proposed weight function. Furthermore, the application of the new weight function, respecting the principle of causality, removes some spurious oscillations appearing with high temporally discontinuous heat sources (such as Heaviside). Results, presented as isotherms or temperature fields, get closer to those obtained with an implicit first-order backward finite–difference scheme.     

Quantitative analysis of technetium-99m-methylene diphosphonate uptake in unilateral hydroxyapatite-coated total hip prostheses: first year of follow-up

A prospective study was performed on 80 patients who had undergone a unilateral hydroxyapatite (HA)-coated total hip arthroplasty to establish the normal periprosthetic uptake of methylenediphosphonate (MDP) as a function of implant age. METHODS: Patients were imaged periodically while they were asymptomatic at 1, 3, 6 and 12 mo postoperatively. Quantitative measurements were performed with a region of interest (ROI) technique. The HA-coated and uncoated areas were marked in comparison with the normal contralateral femur. The uptake ratios of the MDP were determined postoperatively in the following 12 mo. RESULTS: It was found that a decrease of the uptake ratios occurred in all ROIs. However, for the HA-coated areas, the uptake ratios still remained raised as a result of bony ingrowth. CONCLUSION: The results of the first year of follow-up were considered to be a normal database that will be used as a reference when the same group of patients are followed up to 5 yr postoperatively to detect any potential modes of failure of the implant.     

Polypropylene based polymer blends: Fields of application and new trends

The new industrial strategy in the polymer field requires the transformation of plastic “commodities” into “specialties”. From this point of view, polypropylene (PP) plays an important role both for its intrinsic properties such as high melting temperature, low density, high chemical inertness and for its capability to be produced with different morphological and molecular structures, to be modified with the addition of other polymers or mineral fillers and to be grafted with functional groups. The present range of special and reinforced polypropylene grades includes: elastomer-modified PP, elastomer-modified filled PP, glass fiber-reinforced PP, filled PP, esthetic filled PP, flame-retardant PP, and thermoplastic elastomers. New trends for significantly improving this family of polymers involve impact resistance, processability, durability, dimensional stability, elasticity, and surface properties. A positive answer to this complex emerging demand will put, as indicated, in this work, “special and reinforced polypropylene grades” in a position to successfully compete with technopolymers in some important, rapidly growing application sectors.     

A Resource Logic for Multi-Agent Plan Merging

In a multi-agent system, agents are carrying out certain tasks by executing plans. Consequently, the problem of finding a plan, given a certain goal, has been given a lot of attention in the literature. Instead of concentrating on this problem, the focus of this paper is on cooperation between agents which already have constructed plans for their goals. By cooperating, agents might reduce the number of actions they have to perform in order to fulfill their goals. The key idea is that in carrying out a plan an agent possibly produces side products that can be used as resources by other agents. As a result, an other agent can discard some of its planned actions. This process of exchanging products, called plan merging, results in distributed plans in which agents become dependent on each other, but are able to attain their goals more efficiently. In order to model this kind of cooperation, a new formalism is developed in which side products are modeled explicitly. The formalism is a resource logic based on the notions of resource, skill, goal, and service. Starting with some resources, an agent can perform a number of skills in order to produce other resources which suffice to achieve some given goals. Here, a skill is an elementary production process taking as inputs resources satisfying certain constraints. A service is a serial or parallel composition of skills acting as a program. An operational semantics is developed for these services as programs. Using this formalism, an algorithm for plan merging is developed, which is anytime and runs in polynomial time. Furthermore, a variant of this algorithm is proposed that handles the exchange of resources in a more flexible way. The ideas in the paper will be illustrated by an example from public transportation.     

Adhesion of human gingival fibroblasts/<Emphasis Type="Italic">Streptococcus mitis</Emphasis> co-culture on the nanocomposite system Chitlac-nAg

Composite materials are increasingly used as dental restoration. In the field of biomaterials, infections remain the main reason of dental devices failure. Silver, in the form of nanoparticles (AgNPs), ions and salt, well known for its antimicrobial properties, is used in several medical applications in order to avoid bacterial infection. To reduce both bacterial adhesion to dental devices and cytotoxicity against eukaryotic cells, we coated BisGMA/TEGDMA methacrylic thermosets with a new material, Chitlac-nAg, formed by stabilized AgNPs with a polyelectrolyte solution containing Chitlac. Here we analyzed the proliferative and adhesive ability of human gingival fibroblasts (HGFs) on BisGMA/TEGDMA thermosets uncoated and coated with AgNPs in a coculture model system with Streptococcus mitis. After 48 h, HGFs well adhered onto both surfaces, while S. mitis cytotoxic response was higher in the presence of AgNPs coated thermosets. After 24 h thermosets coated with Chitlac as well as those coated with Chitlac-nAg exerted a minimal cytotoxic effect on HGFs, while after 48 h LDH release raised up to 20 %. Moreover the presence of S. mitis reduced this release mainly when HGFs adhered to Chitlac-nAg coated thermosets. The reduced secretion of collagen type I was significant in the presence of both surfaces with the co-culture system even more when saliva is added. Integrin β1 localized closely to cell membranes onto Chitlac-nAg thermosets and PKCα translocated into nuclei. These data confirm that Chitlac-nAg have a promising utilization in the field of restorative dentistry exerting their antimicrobial activity due to AgNPs without cytotoxicity for eukaryotic cells.     

Vascular access for hemodialysis: experience of a team of nephrologists

A survey conducted by Bonucchi et al. underlined the different types of doctors placing arteriovenous fistula (AVF) for hemodialysis in the United States and Europe (in particular Italy). In fact, nephrologists definitely prevail in Italy, where almost 48.8% of nephrologists place an AVF themselves or with the help of a vascular surgeon (26.4%). In Europe, only 35% do so, whereas 89% of AVF are performed by surgeons in the United States. In 98% of the cases occurring at our center, the AVF was placed and reviewed by the nephrologists. This paper reports surgery cases related to the period between January 1983 and September 2006. Over this time, 1386 operations for placing and reviewing vascular access were conducted. Among these, 47 (3.3%) were related to a cuffed central venous catheter (CVC); 1138 (80.2%) related to a distal AVF; 201 (10.6%) related to a proximal AVF; and 51 (3.6%) related to an arteriovenous graft (AVG). In addition, 33 (2.3%) operations performed before January 1983 relating to AV Scribner shunts were included. Arteriovenous fistulas or AVGs were provided to our patients (only 2.6% of them have a CVC), and AVF rescue operations were performed in the shortest possible time with advantages for the patient and his vascular access.     

ADMA/SDMA in Elderly Subjects with Asymptomatic Carotid Atherosclerosis: Values and Site-Specific Association

Asymmetric dimethylarginine (ADMA) is an endogenous nitric oxide synthase (NOS) inhibitor known as a mediator of endothelial dysfunction and atherosclerosis. Circulating ADMA levels are correlated with cardiovascular risk factors such as hypercholesterolemia, arterial hypertension, diabetes mellitus, hyperhomocysteinemia, age and smoking. We assessed the relationship between ADMA values and site-specific association of asymptomatic carotid atherosclerosis (intima-media thickness (CIMT) and plaque) in elderly subjects. One hundred and eighty subjects underwent a complete history and physical examination, determination of serum chemistries and ADMA levels, and carotid ultrasound investigation (CUI). All subjects had no acute or chronic symptoms of carotid atherosclerosis. Statistical analyses showed that high plasma levels of ADMA/SDMA were positively correlated to carotid atherosclerosis (CIMT and plaque) (p < 0.001), with significant site-specific association. Total cholesterol, low density lipoprotein cholesterol, triglycerides and C-reactive protein plasma concentrations were significantly associated with asymptomatic carotid atherosclerosis (p < 0.001). High serum concentrations of ADMA and SDMA were associated with carotid atherosclerotic lesions as measured by CIMT ad plaque and may represent a new marker of asymptomatic carotid atherosclerosis in elderly subjects.     

Color tuning of indium phosphide quantum dots for cadmium‐free quantum dot light‐emitting devices with high efficiency and color saturation

Semiconductor quantum dots (QDs) promise facile color tuning and high color saturation in quantum‐dot light‐emitting devices (QD‐LEDs) by controlling nanoparticle size and size distribution. Here, we demonstrate how this promise can be practically realized for the cadmium‐free InP/ZnSe/ZnS multishell quantum dots. We developed a set of synthesis conditions and core/shell compositions that result in QDs with green, yellow, and red emission color. The QD‐LEDs employing these QDs show efficient electroluminescence (EL) with luminance up to 1800 cd/m² and efficiency up to 5.1 cd/ A . The color coordinates calculated from the EL spectra clearly demonstrate the outstanding color saturation as an outcome of the narrow particle size distribution. These results prove that the performance gap between cadmium‐free and cadmium‐based QDs in QD‐LEDs is shrinking rapidly.     

An alternative space–time meshless method for solving transient heat transfer problems with high discontinuous moving sources

ABSTRACT

The aim of this work is the development of a space–time diffuse approximation meshless method (DAM) to solve heat equations containing discontinuous sources. This work is devoted to transient heat transfer problems with static and moving heat sources applied on a metallic plate and whose power presents temporal discontinuities. The space–time DAM using classical weight function is convenient for continuous transient heat transfer. Nevertheless, for problems including discontinuities, some spurious oscillations for the temperature field occur. A new weight function, respecting the principle of causality, is used to eradicate the physically unexpected oscillations.