Dirichlet Priors for MAP Inference of Protein Conformation Abundances from SAXS

Estimation of mixture coefficients of protein conformations in solution find applications in understanding protein behavior. We describe a method for maximum a posteriori (MAP) estimation of the mixture coefficients of ensemble of conformations in a protein mixture solution using measured small angle X-ray scattering (SAXS) intensities. The proposed method builds upon a model for the measurements of crystallographically determined conformations. Assuming that a priori information on the protein mixture is available, and that priori information follows a Dirichlet distribution, we develop a method to estimate the relative abundances with MAP estimator. The Dirichlet distribution depends on concentration parameters which may not be known in practice and thus need to be estimated. To estimate these unknown concentration parameters we developed an expectation-maximization (EM) method. Adenylate kinase (ADK) protein was selected as the test bed due to its known conformations Beckstein et al. (Journal of Molecular Biology, 394(1), 160 1). Known conformations are assumed to form the full vector bases that span the measurement space. In Monte Carlo simulations, mixture coefficient estimation performances of MAP and maximum likelihood (ML) (which assumes a uniform prior on the mixture coefficients) estimators are compared. MAP estimators using known and unknown concentration parameters are also compared in terms of estimation performances. The results show that prior knowledge improves estimation accuracy, but performance is sensitive to perturbations in the Dirichlet distribution’s concentration parameters. Moreover, the estimation method based on EM algorithm shows comparable results to approximately known prior parameters.     

Advantages of CDMA and spread spectrum techniques over FDMA andTDMA in cellular mobile radio applications

A unified theoretical method for the calculation of the radio capacity of multiple-access schemes such as FDMA (frequency-division multiple access), TDMA (time-division multiple access), CDMA (code-division multiple access) and SSMA (spread-spectrum multiple access) in noncellular and cellular mobile radio systems is presented for AWGN (additive white Gaussian noise) channels. The theoretical equivalence of all the considered multiple-access schemes is found. In a fading multipath environment, which is typical for mobile radio applications, there are significant differences between these multiple-access schemes. These differences are discussed in an illustrative manner revealing several advantages of CDMA and SSMA over FDMA and TDMA. Novel transmission and reception schemes called coherent multiple transmission and coherent multiple reception are briefly presented     

Answer Justification in Diagnostic Expert Systems?Part II: Supporting Plausible Justifications

This paper describes how a new method for answer justification in abductive diagnostic expert systems, presented in a preceding companion paper (Part I), can be supported in a domain-independent fashion. Both the issues of explaining why a disorder is included in a differential diagnosis and why it is ranked the way it is relative to its "competitors" are addressed. This approach to answer justification is then compared to previous work on answer justification in medical expert systems.     

Evaluation of Oxidative Stress Biomarkers,Pro-Inflammatory Cytokines,and Histological Changes in Experimental Hypertension,Dyslipidemia, and Type 1 Diabetes Mellitus

The present study aims to compare the oxidative stress biomarkers, pro-inflammatory cytokines, and histological changes induced by three cardiovascular risk factors, namely, hypertension, dyslipidemia, and type 1 diabetes mellitus. Hypertension was induced with 40 mg/kg body weight (b.w.) of N omega-nitro-L-arginine-methyl (L-NAME) administered orally. Dyslipidemia was induced by the administration of a diet with a high cholesterol (2%) content. Diabetes mellitus was induced by intraperitoneal administration of a single dose of streptozocin (65 mg/kg). Malondialdehyde (MDA) and total oxidative status (TOS) are increased by all three cardiovascular risk factors (up to 207%). The indirect assessment of NO synthesis (NOx) is observed to be reduced after L-NAME administration (43%), and dyslipidemia induction (16%), while type 1 diabetes mellitus is associated with the highest levels of NOx (increased 112%). Hypertension, dyslipidemia, and type 1 diabetes reduced the total antioxidative capacity (TAC) and total thiol (SH) levels (up to 57%). The values of evaluated pro-inflammatory cytokines, tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β), assessed from the ascending aorta were elevated by all three cardiovascular risk factors, with the highest levels induced by type 1 diabetes mellitus (up to 259%). The histopathological examination of the ascending and descending aorta revealed reversible pro-atherogenic changes consisting of the accumulation of lipid droplets in the subendothelial connective tissue on rats with hypertension and dyslipidemia. Irreversible pro-atherogenic changes consisting of a reduction of the specific elasticity of the arteries were observed in rats with type 1 diabetes mellitus. Type 1 diabetes mellitus demonstrates an alteration of the oxidative stress parameters, the elevation of tissue levels of the pro-inflammatory cytokines and causing irreversible pro-atherogenic changes on the aortic wall.     

The Effects of Exercise and Activity-Based Physical Therapy on Bone after Spinal Cord Injury

Spinal cord injury (SCI) produces paralysis and a unique form of neurogenic disuse osteoporosis that dramatically increases fracture risk at the distal femur and proximal tibia. This bone loss is driven by heightened bone resorption and near-absent bone formation during the acute post-SCI recovery phase and by a more traditional high-turnover osteopenia that emerges more chronically, which is likely influenced by the continual neural impairment and musculoskeletal unloading. These observations have stimulated interest in specialized exercise or activity-based physical therapy (ABPT) modalities (e.g., neuromuscular or functional electrical stimulation cycling, rowing, or resistance training, as well as other standing, walking, or partial weight-bearing interventions) that reload the paralyzed limbs and promote muscle recovery and use-dependent neuroplasticity. However, only sparse and relatively inconsistent evidence supports the ability of these physical rehabilitation regimens to influence bone metabolism or to increase bone mineral density (BMD) at the most fracture-prone sites in persons with severe SCI. This review discusses the pathophysiology and cellular/molecular mechanisms that influence bone loss after SCI, describes studies evaluating bone turnover and BMD responses to ABPTs during acute versus chronic SCI, identifies factors that may impact the bone responses to ABPT, and provides recommendations to optimize ABPTs for bone recovery.     

Synthesis,properties, and applications of polylactic acid-based polymers

Polylactic acid (PLA) is known as one of the greatest promising bioabsorbable and compostable polyesters with the capability of high molecular weight synthesis. Lactic acid condensation, azeotropic dehydration, and condensation ring-open polymerize of lactide are three methods for PLA polymerization. Comprehension of material properties is critical for choosing the right processing method and adjusting PLA characteristics. A variety of mechanical properties of this material, from soft and elastic to stiff and high strength makes PLA suitable for a wide range of applications. Besides, PLA can be blended or copolymerized with other polymeric or non-polymeric substances. Thus, this polymer can achieve suitable chemical, mechanical, and rheological properties. Understanding the role of these properties and selecting a suitable processing technique is necessary for its intended consumer and various applications. This study elaborated a general summary of the polymerization, processing, and characteristics of PLA (i.e., structural diversities, rheological performances, mechanical properties, and permeability). Besides, this work presented some information regarding essential factors that can be used for modifying PLA properties to address the requirements for various applications such as biomedical, food packing, biocomposite, and additive manufacturing.     

Eco-friendly flame retardant epoxy nanocomposites based on polyphosphonate and halloysite nanotubes

The preparation of a novel polyphosphonate (PSFR) is described here, starting from phenylphosphonic dichloride and an equimolecular mixture containing equal amounts of two bisphenols, namely 4,4′-dihydroxydiphenyl sulfone and 2-(6-oxido-6H-dibenzo<c,e><1,2>oxaphosphorin-6-yl)-1,4-benzenediol, following the polycondensation reaction in solution. Then, new environmental-friendly nanocomposites having improved flame retardancy have been prepared by incorporating PSFR and halloysite nanotubes (HNTs) into epoxy resin. The effect of PSFR and HNTs contents on the chemical and physical characteristics of epoxy nanocomposites was investigated. The success of the reactions was monitored by infrared spectroscopy (FTIR) while microscopic related techniques (SEM) gave information on the morphology of the products. The thermosets exhibit glass transition temperatures in the range of 62.4–97.1°C and thermal decomposition temperatures in the interval of 296–359°C. The appearance of the char residues obtained by pyrolysis was studied by SEM measurements. The flammability behavior has been studied by microscale combustion calorimetry (MCC) tests. A considerable improvement in the flame retardancy of the thermosets was obtained by simultaneous incorporation of HNTs (10 wt%) and PSFR (equivalent of 1 wt% P) into epoxy resin.     

Effect of Ion Concentration Changes in the Limited Extracellular Spaces on Sarcolemmal Ion Transport and Ca2+ Turnover in a Model of Human Ventricular Cardiomyocyte

We have developed a computer model of human cardiac ventricular myocyte (CVM), including t-tubular and cleft spaces with the aim of evaluating the impact of accumulation-depletion of ions in restricted extracellular spaces on transmembrane ion transport and ionic homeostasis in human CVM. The model was based on available data from human CVMs. Under steady state, the effect of ion concentration changes in extracellular spaces on [Ca²⁺]_i-transient was explored as a function of critical fractions of ion transporters in t-tubular membrane (not documented for human CVM). Depletion of Ca²⁺ and accumulation of K⁺ occurring in extracellular spaces slightly affected the transmembrane Ca²⁺ flux, but not the action potential duration (APD₉₀). The [Ca²⁺]_i-transient was reduced (by 2%–9%), depending on the stimulation frequency, the rate of ion exchange between t-tubules and clefts and fractions of ion-transfer proteins in the t-tubular membrane. Under non-steady state, the responses of the model to changes of stimulation frequency were analyzed. A sudden increase of frequency (1–2.5 Hz) caused a temporal decrease of [Ca²⁺] in both extracellular spaces, a reduction of [Ca²⁺]_i-transient (by 15%) and APD₉₀ (by 13 ms). The results reveal different effects of activity-related ion concentration changes in human cardiac t-tubules (steady-state effects) and intercellular clefts (transient effects) in the modulation of membrane ion transport and Ca²⁺ turnover.     

N‐Arylsulfonyl Indolines as Retinoic Acid Receptor‐Related Orphan Receptor γ (RORγ) Agonists

The nuclear retinoic acid receptor‐related orphan receptor γ (RORγ; NR1F3) is a key regulator of inflammatory gene programs involved in T helper 17 (T_H17) cell proliferation. As such, synthetic small‐molecule repressors (inverse agonists) targeting RORγ have been extensively studied for their potential as therapeutic agents for various autoimmune diseases. Alternatively, enhancing T_H17 cell proliferation through activation (agonism) of RORγ may boost an immune response, thereby offering a potentially new approach in cancer immunotherapy. Herein we describe the development of N‐arylsulfonyl indolines as RORγ agonists. Structure–activity studies reveal a critical linker region in these molecules as the major determinant for agonism. Hydrogen/deuterium exchange coupled to mass spectrometry (HDX‐MS) analysis of RORγ–ligand complexes help rationalize the observed results.     

Organosoluble asymmetric aromatic polyamides bearing pendent phenoxy groups

This study focuses on the synthesis and characterization of new polyamides based on an aromatic asymmetric diamine‐containing phenoxy‐substituted benzophenone segment. Low‐temperature solution polycondensation reactions of this diamine with various aromatic diacid chlorides containing ether, hexafluoroisopropylidene or diphenylsilane groups resulted in polyamides with molecular weights in the range 102 900–113 200 g mol^?1. The structures of these monomers and the corresponding polymers were fully confirmed using elemental analysis and infrared and NMR spectroscopy. All polyamides were easily soluble at room temperature in polar aprotic solvents and even in less polar solvents such as tetrahydrofuran. The polymers showed excellent thermal stability, up to 385 °C, and displayed glass transition temperatures in the range 225–256 °C. All the polymers presented blue florescence upon irradiation with UV light and thus show promise for applications in electroluminescent devices. Copyright © 2011 Society of Chemical Industry