Rheological and drug‐release behaviour of a scleroglucan gel matrix at different drug loadings

The aim of this study was to investigate the drug‐loading effects on release and mechanical properties of a scleroglucan gel, with the intention of considering them in delivery systems formulations. The rheological and kinetic properties of a 2 % w/w scleroglucan gel matrix loaded with 0, 0.02, 0.04, 0.06, 0.2 and 0.4 % w/w of theophylline (Th, used as a model drug) were investigated. Rheological measurements were performed in a controlled‐stress rotational‐shear rheometer under isothermal conditions. For theophylline release from the gel a flat Franz cell was used and the kinetic parameters were derived applying a semi‐empirical power law. The influence of scleroglucan molar weight on kinetic and rheological behaviour was also studied. Results suggest two possible effects of drug loading on the gel network: in the 0.04–0.06 % w/w Th range a plasticizing effect and in the 0.2–0.4 % w/w Th range a rigidization effect. In the first range mentioned, the changes in the gel structural properties tested by means of rheological measurements are coincident with changes in drug‐release kinetics. Copyright © 2005 Society of Chemical Industry     

"What is in a word? No versus Yes differentially engage the lateral orbitofrontal cortex": Correction.

Reports an error in "What is in a word? No versus Yes differentially engage the lateral orbitofrontal cortex" by Nelly Alia-Klein, Rita Z. Goldstein, Dardo Tomasi, Lei Zhang, Stephanie Fagin-Jones, Frank Telang, Gene-Jack Wang, Joanna S. Fowler and Nora D. Volkow (Emotion, 2007[Aug], Vol 7[3], 649-659). The supplemental materials link should appear as follows: http://dx.doi.org/10.1037/1528-3542.7.3.649.supp. (The following abstract of the original article appeared in record 2007-11660-018.) The words "No" and "Yes" are involved in conditioning to prohibit or encourage behavior, respectively. The authors, therefore, hypothesized that these words would be attributed to endogenous valence, activating neuronal circuits involved with valence and emotional control. Functional MRI (fMRI) at 4 Tesla was used to record regional brain activity while participants were exposed to emphatic vocalizations of the words. Results showed that No and Yes were associated with opposite brain-behavior responses; while No was negatively valenced, produced slower response times, and evoked a negative signal in the right lateral orbitofrontal cortex (OFC), Yes was positively valenced, produced faster response times, and evoked a positive signal in a contiguous region of the OFC. Attribution of negative valence to No and trait anger control were associated with increased responsivity of the OFC to No. Inasmuch as sensitivity to the prohibitive command No develops during childhood through interaction with primary caregivers as the first social objects, our findings may implicate the lateral OFC in the neurobiology of emotion regulation and subsequent social development. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Energy efficiency, carbon emissions and economic development in Venezuela

Venezuela's vast natural resource base has largely shaped the nation's economic and energy-use patterns. Major opportunities exist for improving the efficiency of energy use in Venezuela and, consequently, restraining the growth of energy-related carbon emissions. This paper presents a detailed report of one potential development path for Venezuela and estimates the ensuing levels of energy demand and CO₂ emissions associated with pursuing this path through the year 2025. The results indicate that by adopting a development strategy that incorporates structural changes in the economy, fuel-switching measures and improved end-use efficiencies, Venezuela can introduce energy efficiency and carbon restraints as part of its economic development process.     

Matching treatment focus to patient social investment and support: 18-month follow-up results.

Patients were randomly assigned to 1 of 3 treatments: brief broad-spectrum (BBS), extended relationship enhancement (ERE), or extended cognitive–behavioral (ECB). A hierarchical latent growth model was used to analyze the data of 188 patients (82%) followed for 18 months. ERE treatment was significantly more effective in increasing abstinence of patients entering treatment with a network unsupportive of abstinence or with a low level of investment in their network, whereas BBS treatment was more effective for patients with either (a) both a social network unsupportive of abstinence and a low level of network investment or (b) high investment in a network supportive of abstinence. ECB outcomes were neither as good as those matched nor as bad as those mismatched to the different exposures of relationship enhancement. This suggests that dose of relationship enhancement should be determined after assessing patient relationships. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Aqueous electrochemical intercalation of bromine into graphite fibers

For the first time, graphite fibers have been electrochemically intercalated with Br⁻ that have the same structure and properties as those intercalated from vapor phase Br₂. This was accomplished by intercalating pitch-based Thornel^® K-1100 graphite fibers at low temperature (near 0 °C) and high currents (2 A) for long times (6 h). The mechanism appears to be that Br⁻ is oxidized to aqueous Br₂ which, when sufficient local concentration builds up, intercalates the fiber. This was confirmed by intercalating K-1100 fiber in a saturated aqueous Br₂ solution without passing an electrical current. The applied voltage does apparently lower the activation energy of the reaction as evidenced by the observation that P-120 and P-100 fibers will not intercalate in aqueous Br₂ unless a voltage is applied.     

Non-functional properties in the model-driven development of service-oriented systems

Systems based on the service-oriented architecture (SOA) principles have become an important cornerstone of the development of enterprise-scale software applications. They are characterized by separating functions into distinct software units, called services, which can be published, requested and dynamically combined in the production of business applications. Service-oriented systems (SOSs) promise high flexibility, improved maintainability, and simple re-use of functionality. Achieving these properties requires an understanding not only of the individual artifacts of the system but also their integration. In this context, non-functional aspects play an important role and should be analyzed and modeled as early as possible in the development cycle. In this paper, we discuss modeling of non-functional aspects of service-oriented systems, and the use of these models for analysis and deployment. Our contribution in this paper is threefold. First, we show how services and service compositions may be modeled in UML by using a profile for SOA (UML4SOA) and how non-functional properties of service-oriented systems can be represented using the non-functional extension of UML4SOA (UML4SOA-NFP) and the MARTE profile. This enables modeling of performance, security and reliable messaging. Second, we discuss formal analysis of models which respect this design, in particular we consider performance estimates and reliability analysis using the stochastically timed process algebra PEPA as the underlying analytical engine. Last but not least, our models are the source for the application of deployment mechanisms which comprise model-to-model and model-to-text transformations implemented in the framework VIATRA. All techniques presented in this work are illustrated by a running example from an eUniversity case study.     

Modeling contextual security policies

As computer infrastructures become more complex, security models must provide means to handle more flexible and dynamic requirements. In the Organization Based Access Control (OrBAC) model, it is possible to express such requirements using the notion of context. In OrBAC, each security rule (permission, prohibition, obligation or dispensation) only applies in a given context. A context is viewed as an extra condition that must be satisfied to activate a given security rule. In this paper, we present a taxonomy of different types of context and investigate the data the information system must manage in order to deal with these different contexts. We then explain how to model and evaluate them in the OrBAC model.

Early Osteogenic Marker Expression in hMSCs Cultured onto Acid Etching-Derived Micro- and Nanotopography 3D-Printed Titanium Surfaces

Polyetheretherketone (PEEK) titanium composite (PTC) is a novel interbody fusion device that combines a PEEK core with titanium alloy (Ti6Al4V) endplates. The present study aimed to investigate the in vitro biological reactivity of human bone-marrow-derived mesenchymal stem cells (hBM-MSCs) to micro- and nanotopographies produced by an acid-etching process on the surface of 3D-printed PTC endplates. Optical profilometer and scanning electron microscopy were used to assess the surface roughness and identify the nano-features of etched or unetched PTC endplates, respectively. The viability, morphology and the expression of specific osteogenic markers were examined after 7 days of culture in the seeded cells. Haralick texture analysis was carried out on the unseeded endplates to correlate surface texture features to the biological data. The acid-etching process modified the surface roughness of the 3D-printed PTC endplates, creating micro- and nano-scale structures that significantly contributed to sustaining the viability of hBM-MSCs and triggering the expression of early osteogenic markers, such as alkaline phosphatase activity and bone-ECM protein production. Finally, the topography of 3D-printed PTC endplates influenced Haralick’s features, which in turn correlated with the expression of two osteogenic markers, osteopontin and osteocalcin. Overall, these data demonstrate that the acid-etching process of PTC endplates created a favourable environment for osteogenic differentiation of hBM-MSCs and may potentially have clinical benefit.     

Enapotamab Vedotin,an AXL-Specific Antibody-Drug Conjugate,Demonstrates Antitumor Efficacy in Patient-Derived Xenograft Models of Soft Tissue Sarcoma

Doxorubicin (doxo) remains the standard of care for patients with advanced soft tissue sarcoma (STS), even though response rates to doxo are only around 14% to 18%. We evaluated enapotamab vedotin (EnaV), an AXL-specific antibody-drug conjugate (ADC), in a panel of STS patient-derived xenografts (PDX). Eight models representing multiple STS subtypes were selected from our STS PDX platform (n = 45) by AXL immunostaining on archived passages. Models were expanded by unilateral transplantation of tumor tissue into the left flank of 20 NMRI nu/nu mice. Once tumors were established, mice were randomized into an EnaV treatment group, or a group treated with isotype control ADC. Treatment efficacy was assessed by tumor volume evaluation, survival analysis, and histological evaluation of tumors, and associated with AXL expression. EnaV demonstrated significant tumor growth delay, regression, and/or prolonged survival compared to isotype control ADC in 5/8 STS PDX models investigated. Experimental passages of responding models were all found positive for AXL at varying levels, but no linear relationship could be identified between the level of expression and level of response to EnaV. One model was found negative for AXL on experimental passage and did not respond to EnaV. This study provides a preclinical rationale for the evaluation of AXL-targeting ADCs in the treatment of AXL-expressing sarcomas.     

A general technique for derivation of average current mode controllaws for single-phase power-factor-correction circuits without inputvoltage sensing

This paper presents a general technique to derive average current mode control (CMC) laws without input voltage sensing to achieve high power factor for single-phase topologies operating in continuous conduction mode (CCM). The control laws are derived based on the steady-state input-output voltage relationships and the CCM large-signal averaged pulsewidth modulation (PWM)-switch model. Using this methodology, average CMC laws with linear PWM waveforms are discovered for commonly used single-phase power stage topologies such as boost, flyback, SEPIC, and buck/boost. Conventional three-loop-controlled average CMC converters can now be controlled with a two-loop architecture. Hardware results for a boost power factor correction (PFC) and simulation results for flyback, SEPIC, and buck/boost topologies verify operation. The small-signal models of the current loop and voltage loop are derived for the boost topology and are used for control loop design. Input current harmonic distortion measurements demonstrate improved performance compared to the conventional three-loop control technique