bluuebunny/crossref_metadata_2025 huggingface dataset:
Synbiotics in Health and Disease
Authors: Kolida Sofia , Gibson Glenn R.
Published: May 2012

The synbiotic concept was first introduced, along with prebiotics, as “mixtures of probiotics and prebiotics that beneficially affect the host by improving the survival and implantation of live microbial dietary supplements in the gastrointestinal tract, by selectively stimulating the growth and/or by activating the metabolism of one or a limited number of health-promoting bacteria, thus improving host welfare” ( Gibson & Roberfroid 1995 ). Since, there have been many in vitro and in vivo studies focusing on the application of prebiotics, firstly in health and gradually in disease states. Only recently have studies on synbiotics started to emerge with the main focus being on applications against disease. Here, we review the current literature, with the main focus on in vivo human studies.
The Influence of Milk Oligosaccharides on Microbiota of Infants: Opportunities for Formulas
Authors: Chichlowski Maciej , German J. Bruce , Lebrilla Carlito B. , Mills David A.
Published: May 2012

In addition to a nutritive role, human milk also guides the development of a protective intestinal microbiota in the infant. Human milk possesses an overabundance of complex oligosaccharides that are indigestible by the infant yet are consumed by microbial populations in the developing intestine. These oligosaccharides are believed to facilitate enrichment of a healthy infant gastrointestinal microbiota, often associated with bifidobacteria. Advances in glycomics have enabled precise determination of milk glycan structures as well as identification of the specific glycans consumed by various gut microbes. Furthermore, genomic analysis of bifidobacteria from infants has revealed specific genetic loci related to milk oligosaccharide import and processing, suggesting coevolution between the human host, milk glycans, and the microbes they enrich. This review discusses the current understanding of how human milk oligosaccharides interact with the infant microbiota and examines the opportunities for translating this knowledge to improve the functionality of infant formulas.
Cold Plasma Decontamination of Foods
Authors: Niemira Brendan A.
Published: May 2012

Cold plasma is a novel nonthermal food processing technology that uses energetic, reactive gases to inactivate contaminating microbes on meats, poultry, fruits, and vegetables. This flexible sanitizing method uses electricity and a carrier gas, such as air, oxygen, nitrogen, or helium; antimicrobial chemical agents are not required. The primary modes of action are due to UV light and reactive chemical products of the cold plasma ionization process. A wide array of cold plasma systems that operate at atmospheric pressures or in low pressure treatment chambers are under development. Reductions of greater than 5 logs can be obtained for pathogens such as Salmonella, Escherichia coli O157:H7, Listeria monocytogenes, and Staphylococcus aureus. Effective treatment times can range from 120 s to as little as 3 s, depending on the food treated and the processing conditions. Key limitations for cold plasma are the relatively early state of technology development, the variety and complexity of the necessary equipment, and the largely unexplored impacts of cold plasma treatment on the sensory and nutritional qualities of treated foods. Also, the antimicrobial modes of action for various cold plasma systems vary depending on the type of cold plasma generated. Optimization and scale up to commercial treatment levels require a more complete understanding of these chemical processes. Nevertheless, this area of technology shows promise and is the subject of active research to enhance efficacy.
Food Safety and Organic Meats
Authors: Van Loo Ellen J. , Alali Walid , Ricke Steven C.
Published: May 2012

The organic meat industry in the United States has grown substantially in the past decade in response to consumer demand for nonconventionally produced products. Consumers are often not aware that the United States Department of Agriculture (USDA) organic standards are based only on the methods used for production and processing of the product and not on the product's safety. Food safety hazards associated with organic meats remain unclear because of the limited research conducted to determine the safety of organic meat from farm-to-fork. The objective of this review is to provide an overview of the published results on the microbiological safety of organic meats. In addition, antimicrobial resistance of microbes in organic food animal production is addressed. Determining the food safety risks associated with organic meat production requires systematic longitudinal studies that quantify the risks of microbial and nonmicrobial hazards from farm-to-fork.
Internalization of Fresh Produce by Foodborne Pathogens
Authors: Erickson Marilyn C.
Published: May 2012

Recent studies addressing the internalization of fresh produce by foodborne pathogens arose in response to the growing number of recent and high profile outbreaks involving fresh produce. Because chemical sanitizing agents used during harvest and minimal processing are unlikely to reach enteric pathogens residing within plant tissue, it is imperative that paths for pathogen entry be recognized and minimized. Using both microscopy and microbial enumeration tools, enteric pathogens have been shown to enter plant tissues through both natural apertures (stomata, lateral junctions of roots, flowers) and damaged (wounds, cut surfaces) tissue. In studies revealing preharvest internalization via plant roots or leaf stomata, experimental conditions have primarily involved exposure of plants to high pathogen concentrations (≥6 log g−1 soil or 6 log ml−1 water), but those pathogens internalized appear to have short-term persistence. Postharvest internalization of pathogens via cut surfaces may be minimized by maintaining effective levels of sanitizing agents in waters during harvesting and minimal processing.
The Structure of the Casein Micelle of Milk and Its Changes During Processing
Authors: Dalgleish Douglas G. , Corredig Milena
Published: May 2012

The majority of the protein in cow's milk is contained in the particles known as casein micelles. This review describes the main structural features of these particles and the different models that have been used to define the interior structures. The reactions of the micelles during processing operations are described in terms of the structural models.
Novel Natural Food Antimicrobials
Authors: Juneja Vijay K. , Dwivedi Hari P. , Yan Xianghe
Published: May 2012

Naturally occurring antimicrobial compounds could be applied as food preservatives to protect food quality and extend the shelf life of foods and beverages. These compounds are naturally produced and isolated from various sources, including plants, animals and microorganisms, in which they constitute part of host defense systems. Many naturally occurring compounds, such as nisin, plant essential oils, and natamycin, have been widely studied and are reported to be effective in their potential role as antimicrobial agents against spoilage and pathogenic microorganisms. Although some of these natural antimicrobials are commercially available and applied in food processing, their efficacy, consumer acceptance and regulation are not well defined. This manuscript reviews natural antimicrobial compounds with reference to their applications in food when applied individually or in combination with other hurdles. It also reviews the mechanism of action of selected natural antimicrobials, factors affecting their antimicrobial activities, and future prospects for use of natural antimicrobials in the food industry.
Polymer and Colloidal Models Describing Structure-Function Relationships
Authors: Ikeda Shinya , Zhong Qixin
Published: May 2012

Colloidal and polymer systems are not only abundant in food but also useful for gaining insights into structure-function relationships of food. Colloid and polymer systems are composed of mesoscopic scale particles dispersed in a liquid. Because of a relatively small potential barrier against aggregation between mesoscopic particles, a small change in temperature, pH, or chemical compositions can trigger aggregation and induce remarkable changes in structure and function of colloidal and polymer systems. An aggregated state is not normally an equilibrium state but a kinetically trapped state also called a jammed state. Various kinetic factors in food processing, such as the rate of changes in temperature, water content, and chemical compositions, must be taken into account to establish a complete state diagram of colloid- and polymer-based food systems.
Lessons Learned
Authors: Hall Richard L.
Published: May 2012

The paper discusses my early years, education, and life experiences, including aspects of my career at McCormick & Co., Inc. A major intensive effort, one that greatly influenced my career, was helping the flavor industry cope with the passage of the Food Additives Amendment to the Food, Drug, and Cosmetic Act. It resulted in a program now in its 51st year that is unique in the food industry. Other activities took me further into the fields of toxicology, structure/activity relationships, food safety, nutrition, and biotechnology. The paper closes with some observations on current challenges, and the steps that, in my opinion, we must take to meet them.
Aerobic Respiration Metabolism in Lactic Acid Bacteria and Uses in Biotechnology
Authors: Pedersen Martin B. , Gaudu Philippe , Lechardeur Delphine , Petit Marie-Agnès , Gruss Alexandra
Published: May 2012

The lactic acid bacteria (LAB) are essential for food fermentations and their impact on gut physiology and health is under active exploration. In addition to their well-studied fermentation metabolism, many species belonging to this heterogeneous group are genetically equipped for respiration metabolism. In LAB, respiration is activated by exogenous heme, and for some species, heme and menaquinone. Respiration metabolism increases growth yield and improves fitness. In this review, we aim to present the basics of respiration metabolism in LAB, its genetic requirements, and the dramatic physiological changes it engenders. We address the question of how LAB acquired the genetic equipment for respiration. We present at length how respiration can be used advantageously in an industrial setting, both in the context of food-related technologies and in novel potential applications.
Wheat Gluten Functionality as a Quality Determinant in Cereal-Based Food Products
Authors: Delcour Jan A. , Joye Iris J. , Pareyt Bram , Wilderjans Edith , Brijs Kristof , Lagrain Bert
Published: May 2012

The unique properties of wheat reside primarily in its gluten-forming storage proteins. Their intrinsic viscoelastic behavior is responsible for the characteristics of different wheat-based foods and for the use of wheat gluten proteins in different food products. Wheat-based food processing generally develops and sets the gluten protein network. Heat-induced gluten aggregation proceeds through cross-linking within and between its protein fractions. Prominent reactions include sulfhydryl (SH) oxidation and SH-disulfide (SS) interchange, which lead to SS cross-links. Other covalent bonds are also formed. Gluten functionality can be (bio-) chemically impacted. We focus on bread making, in which gluten proteins contribute to dough properties, bread loaf volume, and structure, and on pasta production, in which gluten proteins generate the desired cooking quality. Furthermore, it is speculated that the structure and texture of soft wheat products are also, at least to some degree, shaped by the heat-induced changes in the gluten protein fraction.
Emerging Technologies in Food Processing
Authors: Knorr D. , Froehling A. , Jaeger H. , Reineke K. , Schlueter O. , Schoessler K.
Published: May 2012

High hydrostatic pressure (HHP), pulsed electric fields (PEFs), ultrasound (US), and cold plasma (CP) are emerging technologies that have already found application in the food industry or related sectors. This review aims to describe the basic principles of these nonthermal technologies as well as the state of the art concerning their impact on biological cells, enzymes, and food constituents. Current and potential applications will be discussed, focusing on process-structure-function relationships, as well as recent advances in the process development.
Nutrigenomics and Personalized Diets: What Will They Mean for Food?
Authors: German J. Bruce , Zivkovic Angela M. , Dallas David C. , Smilowitz Jennifer T.
Published: May 2012

The modern food system feeds six billion people with remarkable diversity, safety, and nutrition. Yet, the current rise in diet-related diseases is compromising health and devaluing many aspects of modern agriculture. Steps to increase the nutritional quality of individual foods will assist in personalizing health and in guiding individuals to achieve superior health. Nutrigenomics is the scientific field of the genetic basis for varying susceptibilities to disease and the diverse responses to foods. Although some of these genetic determinants will be simple and amenable to personal genotyping as the means to predict health, in practice most will not. As a result, genotyping will not be the secret to personalizing diet and health. Human assessment technologies from imaging to proteomics and metabolomics are providing tools to both understand and accurately assess the nutritional phenotype of individuals. The business models are also emerging to bring these assessment capabilities to industrial practice, in which consumers will know more about their personal health and seek personal solutions.
Bile salts disrupt human esophageal squamous epithelial barrier function by modulating tight junction proteins
Authors: Chen Xin , Oshima Tadayuki , Shan Jing , Fukui Hirokazu , Watari Jiro , Miwa Hiroto
Published: May 2012

Reflux of acid and bile acids contributes to epithelial tissue injury in gastro-esophageal reflux disease. However, the influence of refluxed material on human esophageal stratified epithelial barrier function and tight junction (TJ) proteins has not been fully elucidated. Here, we investigated the influence of acid and bile acids on barrier function and TJ protein distribution using a newly developed air-liquid interface (ALI) in vitro culture model of stratified squamous epithelium based on primary human esophageal epithelial cells (HEECs). Under ALI conditions, HEECs formed distinct epithelial layers on Transwell inserts after 7 days of culture. The epithelial layers formed TJ, and the presence of claudin-1, claudin-4, and occludin were detected by immunofluorescent staining. The NP-40-insoluble fraction of these TJ proteins was significantly higher by day 7 of ALI culture. Exposure of HEECs to pH 2, and taurocholic acid (TCA) and glycocholic acid (GCA) at pH 3, but not pH 4, for 1 h decreased transepithelial electrical resistance (TEER) and increased paracellular permeability. Exposure of cell layers to GCA (pH 3) and TCA (pH 3) for 1 h also markedly reduced the insoluble fractions of claudin-1 and -4. We found that deoxycholic acid (pH 7.4 or 6, 1 h) and pepsin (pH 3, 24 h) significantly decreased TEER and increased permeability. Based on these findings, ALI-cultured HEECs represent a new in vitro model of human esophageal stratified epithelium and are suitable for studying esophageal epithelial barrier functions. Using this model, we demonstrated that acid, bile acids, and pepsin disrupt squamous epithelial barrier function partly by modulating TJ proteins. These results provide new insights into understanding the role of TJ proteins in esophagitis.
Do mice bred selectively for high locomotor activity have a greater reliance on lipids to power submaximal aerobic exercise?
Authors: Templeman Nicole M. , Schutz Heidi , Garland Theodore , McClelland Grant B.
Published: May 2012

Patterns of fuel use during locomotion are determined by exercise intensity and duration, and are remarkably similar across many mammalian taxa. However, as lipids have a high yield of ATP per mole and are stored in large quantities, their use should be favored in endurance-adapted animals. To examine the capacity for alteration or differential regulation of fuel-use patterns, we studied two lines of mice that had been selectively bred for high voluntary wheel running (HR), including one characterized by small hindlimb muscles (HRmini) and one without this phenotype (HRnormal), as well as a nonselected control line. We evaluated: 1) maximal aerobic capacity (V̇o2 max); 2) whole body fuel use during exercise by indirect calorimetry; 3) cardiac properties; and 4) many factors involved in regulating lipid use. HR mice achieved an increased V̇o2 maxcompared with control mice, potentially in part due to HR cardiac capacities for metabolic fuel oxidation and the larger relative heart size of HRminimice. HR mice also exhibited enhanced whole body lipid oxidation rates at 66% V̇o2 max, but HRmini, HRnormal, and control mice did not differ in the proportional mix of fuels sustaining exercise (% total V̇o2). However, HRminigastrocnemius muscle had elevated fatty acid translocase (FAT/CD36) sarcolemmal protein and cellular mRNA, fatty acid binding protein (H-FABP) cytosolic protein, peroxisome proliferator-activated receptor ( PPAR) α mRNA, and mass-specific activities of citrate synthase, β-hydroxyacyl-CoA dehydrogenase, and hexokinase. Therefore, high-running mouse lines had whole body fuel oxidation rates commensurate with maximal aerobic capacity, despite notable differences in skeletal muscle metabolic phenotypes.
The epithelial sodium channel δ-subunit: new notes for an old song
Authors: Giraldez Teresa , Rojas Patricio , Jou Jonathan , Flores Carlos , Alvarez de la Rosa Diego
Published: May 2012

Amiloride-sensitive epithelial Na+ channels (ENaCs) can be formed by different combinations of four homologous subunits, named α, β, γ, and δ. In addition to providing an apical entry pathway for transepithelial Na+ reabsorption in tight epithelia such as the kidney distal tubule and collecting duct, ENaCs are also expressed in nonepithelial cells, where they may play different functional roles. The δ-subunit of ENaC was originally identified in humans and is able to form amiloride-sensitive Na+ channels alone or in combination with β and γ, generally resembling the canonical kidney ENaC formed by α, β, and γ. However, δ differs from α in its tissue distribution and channel properties. Despite the low sequence conservation between α and δ (37% identity), their similar functional characteristics provide an excellent model for exploring structural correlates of specific ENaC biophysical and pharmacological properties. Moreover, the study of cellular mechanisms modulating the activity of different ENaC subunit combinations provides an opportunity to gain insight into the regulation of the channel. In this review, we examine the evolution of ENaC genes, channel subunit composition, the distinct functional and pharmacological features that δ confers to ENaC, and how this can be exploited to better understand this ion channel. Finally, we briefly consider possible functional roles of the ENaC δ-subunit.
Temporal expression of the PGE2 synthetic system in the kidney is associated with the time frame of renal developmental vulnerability to cyclooxygenase-2 inhibition
Authors: Frölich Stefanie , Olliges Anke , Kern Niklas , Schreiber Yannik , Narumiya Shuh , Nüsing Rolf M.
Published: May 2012

Pharmacological blockade of cyclooxygenase-2 (COX-2) causes impairment of kidney development. The present study was aimed at determining temporal expression pattern and activity of the PGE2 synthetic pathway during postnatal nephrogenesis in mice and its association to the time window sensitive to COX-2 inhibition. During the first 10 days after birth, we observed transient induction of mRNA and protein for microsomal PGE synthase (mPGES)-1 between postnatal days 4 ( P4) and P8, but not for mPGES-2 or cytosolic PGE synthase (cPGES). PGE2 synthetic activity using arachidonic acid and PGH2 as substrates and also urinary excretion of PGE2 were enhanced during this time frame. In parallel to the PGE2 system, COX-2 but not COX-1 expression was also transiently induced. Studying glomerulogenesis in EP receptor knockout mice revealed a reduction in glomerular size in EP1−/−, EP2−/−, and EP4−/− mice, supporting the developmental role of PGE2. The most vulnerable time window to COX-2 inhibition by SC-236 was found closely related to the temporal expression of COX-2 and mPGES-1. The strongest effects of COX-2 inhibition were achieved following 8 days of drug administration. Similar developmental damage was caused by application of rofecoxib, but not by the COX-1-selective inhibitor SC-560. COX-2 inhibition starting after P10 has had no effect on the size of glomeruli or on the relative number of superficial glomeruli; however, growth of the renal cortex was significantly diminished, indicating the requirement of COX-2 activity after P10. Effects of COX-2 inhibition on renal cell differentiation and on renal fibrosis needed a prolonged time of exposition of at least 10 days. In conclusion, temporal expression of the PGE2 synthetic system coincides with the most vulnerable age interval for the induction of irreversible renal abnormalities. We assume that mPGES-1 is coregulated with COX-2 for PGE2 synthesis to orchestrate postnatal kidney development and growth.
Membrane properties and electrogenesis in the distal axons of small dorsal root ganglion neurons in vitro
Authors: Vasylyev Dmytro V. , Waxman Stephen G.
Published: May 2012

Although it is generally thought that sensory transduction occurs at or close to peripheral nerve endings, with action potentials subsequently propagating along the axons of dorsal root ganglia (DRG) neurons toward the central nervous system, the small diameter of nociceptive axons and their endings have made it difficult to estimate their membrane properties and electrogenic characteristics. Even the resting potentials of nociceptive axons are unknown. In this study, we developed the capability to record directly with patch-clamp electrodes from the small-diameter distal axons of DRG neurons in vitro. We showed using current-clamp recordings that 1) these sensory axons have a resting potential of −60.2 ± 1 mV; 2) both tetrodotoxin (TTX)-sensitive (TTX-S) and TTX-resistant (TTX-R) Na+ channels are present and available for activation at resting potential, at densities that can support action potential electrogenesis in these axons; 3) TTX-sensitive channels contribute to the amplification of small depolarizations that are subthreshold with respect to the action potential in these axons; 4) TTX-R channels can support the production of action potentials in these axons; and 5) these TTX-R channels can produce repetitive firing, even at depolarized membrane potentials where TTX-S channels are inactivated. Finally, using voltage-clamp recordings with an action potential as the command, we confirmed the presence of both TTX-S and TTX-R channels, which are activated sequentially during action potential in these axons. These results provide direct evidence for the presence of TTX-S and TTX-R Na+ channels that are functionally available at resting potential and contribute to electrogenesis in small-diameter afferent axons.
Excitatory effects of GABA on procerebrum neurons in a slug
Authors: Kobayashi Suguru , Matsuo Ryota , Sadamoto Hisayo , Watanabe Satoshi , Ito Etsuro
Published: May 2012

Classical neurotransmitters, such as glutamate and γ-aminobutyric acid (GABA), often have different actions on invertebrate neurons from those reported for vertebrate neurons. In the terrestrial mollusk Limax, glutamate was found to function as an inhibitory transmitter in the procerebrum (PC), but it has not yet been clarified how GABA acts in the PC. We thus examined what effects GABA exerts on PC neurons in the present study. For this purpose, we first applied GABA to isolated PC preparations and recorded postsynaptic currents and potentials in PC neurons. The GABA application reduced the amplitude of inhibitory postsynaptic currents and depolarization-induced outward currents recorded in nonbursting neurons and increased the number of spontaneous spikes of nonbursting neurons. However, direct GABA-induced currents were not observed in either bursting or nonbursting neurons. These results suggest a potential direct effect of GABA on outward currents resulting in enhanced excitability of PC neurons. Next, we measured the change in [Ca2+]iin cultured PC neurons by application of GABA. The GABA application increased spontaneous Ca2+events in cultured neurons. These Ca2+events were ascribable to the influx of extracellular Ca2+. We then confirmed the presence of GABA and GABA receptors in the PC. The GABA-like immunoreactivity was observed in the neuropil layers of the PC, and the mRNAs for both GABAAand GABABreceptors were expressed in the PC. In particular, GABABreceptor mRNA, rather than GABAA, was found to be more abundantly expressed in the PC. These results suggest that GABA functions as an excitatory modulator for PC neurons via mainly GABABreceptors.
Comparison of Raw Dairy Manure Slurry and Anaerobically Digested Slurry as N Sources for Grass Forage Production
Authors: Saunders Olivia E. , Fortuna Ann-Marie , Harrison Joe H. , Whitefield Elizabeth , Cogger Craig G. , Kennedy Ann C. , Bary Andy I.
Published: May 2012

We conducted a 3-year field study to determine how raw dairy slurry and anaerobically digested slurry (dairy slurry and food waste) applied via broadcast and subsurface deposition to reed canarygrass (Phalaris arundinacea) affected forage biomass, N uptake, apparent nitrogen recovery (ANR), and soil nitrate concentrations relative to urea. Annual N applications ranged from 600 kg N ha−1in 2009 to 300 g N ha−1in 2011. Forage yield and N uptake were similar across slurry treatments. Soil nitrate concentrations were greatest at the beginning of the fall leaching season, and did not differ among slurry treatments or application methods. Urea-fertilized plots had the highest soil nitrate concentrations but did not consistently have greatest forage biomass. ANR for the slurry treatments ranged from 35 to 70% when calculations were based on ammonium-N concentration, compared with 31 to 65% for urea. Slurry ANR calculated on a total N basis was lower (15 to 40%) due to lower availability of the organic N in the slurries. No consistent differences in soil microbial biomass or other biological indicators were observed. Anaerobically digested slurry supported equal forage production and similar N use efficiency when compared to raw dairy slurry.
Point Pattern Matching Algorithm for Planar Point Sets under Euclidean Transform
Authors: Wang Xiaoyun , Zhang Xianquan
Published: May 2012

Point pattern matching is an important topic of computer vision and pattern recognition. In this paper, we propose a point pattern matching algorithm for two planar point sets under Euclidean transform. We view a point set as a complete graph, establish the relation between the point set and the complete graph, and solve the point pattern matching problem by finding congruent complete graphs. Experiments are conducted to show the effectiveness and robustness of the proposed algorithm.
IgG4-Related Disease Is Not Associated with Antibody to the Phospholipase A2 Receptor
Authors: Khosroshahi Arezou , Ayalon Rivka , Beck Laurence H. , Salant David J. , Bloch Donald B. , Stone John H.
Published: May 2012

Patients with IgG4-related disease (IgG4-RD) share histopathological characteristics that are similar across affected organs. The finding of infiltration with IgG4+ plasma cells in the proper clinical and histopathological contexts connects a large number of clinical entities that were viewed previously as separate conditions. The renal involvement in IgG4-RD is usually characterized by tubulointerstitial nephritis, but membranous nephropathy has also been reported to be one of the renal complications of IgG4-RD. The recent discovery that a high proportion of patients with idiopathic membranous nephropathy (IMN) have IgG4 autoantibodies to the M-type phospholipase A2 receptor (PLA2R) in the circulation and glomerular immune deposits, together with the profound IgG4 hypergammaglobulinemia and occasional reports of membranous nephropathy in IgG4-RD, raised the question of a common antigen. To assess the presence of anti-PLA2R antibody in patients with IgG4-RD, we screened sera from 28 IgG4-RD patients by immunoblot. None of the patients in this cohort had detectable circulating anti-PLA2R antibodies. This study suggests that despite some clinical and serological overlaps between IgG4-RD and IMN,anti-PLA2R antibodies do not play a role in the pathogenesis of IgG4-RD. Additional studies of IgG4-RD with evidence of membranous nephropathy are important to exclude any definite relationship.
Fault Detection of Markov Jumping Linear Systems
Authors: Li Wei , Jiang Fan , Wang Zhongqiu , Zhou Gongbo , Zhu Zhencai
Published: May 2012

In this paper, the fault detection (FD) problems of discrete‐time Markov jumping linear systems (MJLSs) are studied. We first focus on the stationary MJLS. The proposed FD system consists of two steps: residual generation and residual evaluation. A new reference model strategy is applied to construct a residual generator, such that it is robust against disturbances and sensitive to system faults. The generated residual signals are then evaluated according to their stochastic properties, and a threshold is computed for detecting the occurrences of faults. The upper bound of the corresponding false alarm rate (FAR) is also given. For the nonstationary MJLS, similar results are also obtained. All the solutions are presented in the form of linear matrix inequalities (LMIs). Finally, a numerical example is used to illustrate the results.
Developing Policy for Integrating Biomedicine and Traditional Chinese Medical Practice Using Focus Groups and the Delphi Technique
Authors: Chung Vincent C. H. , Ma Polly H. X. , Lau Chun Hong , Griffiths Sian M.
Published: May 2012

In Hong Kong, statutory regulation for traditional Chinese medicine (TCM) practitioners has been implemented in the past decade. Increasing use of TCM on top of biomedicine (BM) services by the population has been followed; but corresponding policy development to integrate their practices has not yet been discussed. Using focus group methodology, we explore policy ideas for integration by collating views from frontline BM (n=50) and TCM clinicians (n=50). Qualitative data were analyzed under the guidance ofstructuration model of collaboration, a theoretical model for understanding interprofessional collaboration. From focus group findings we generated 28 possible approaches, and subsequently their acceptability was assessed by a two round Delphi survey amongst BM and TCM policy stakeholders (n=12). Consensus was reached only on 13 statements. Stakeholders agreed that clinicians from both paradigms should share common goals of providing patient-centered care, promoting the development of protocols for shared care and information exchange, as well as strengthening interprofessional connectivity and leadership for integration. On the other hand, attitudes amongst policy stakeholders were split on the possibility of fostering trust and mutual learning, as well as on enhancing innovation and governmental support. Future policy initiatives should focus on these controversial areas.
Commercial Dengue Rapid Diagnostic Tests for Point-of-Care Application: Recent Evaluations and Future Needs?
Authors: Blacksell Stuart D.
Published: May 2012

Dengue fever, dengue haemorrhagic fever, and dengue shock syndrome (DF/DHF/DSS) are tropical diseases that cause significant humanitarian and economic hardship. It is estimated that more than 2.5 billion people are at risk of infection and more than 100 countries have endemic dengue virus transmission. Laboratory tests are essential to provide an accurate diagnosis of dengue virus infection so that appropriate treatment and patient management may be administered. In many dengue endemic settings, laboratory diagnostic resources are limited and simple rapid diagnostic tests (RDTs) provide opportunities for point-of-care diagnosis. This paper addresses current issues relating to the application of commercial dengue RDTs for the diagnosis of acute dengue virus infection, recent diagnostic evaluations, and identifies future needs.
Changes of TSH-Stimulation Blocking Antibody (TSBAb) and Thyroid Stimulating Antibody (TSAb) Over 10 Years in 34 TSBAb-Positive Patients with Hypothyroidism and in 98 TSAb-Positive Graves’ Patients with Hyperthyroidism: Reevaluation of TSBAb and TSAb in TSH-Receptor-Antibody (TRAb)-Positive Patients
Authors: Takasu Nobuyuki , Matsushita Mina
Published: May 2012

Two TRAbs: TSBAb and TSAb. TSBAb causes hypothyroidism. TSAb causes Graves’ hyperthyroidism. TSBAb and TSAb block TSH-binding to cells as TRAb, measured as TSH-binding inhibitory immunoglobulin (TBII). We reevaluate TSBAb and TSAb. We studied TSBAb, TSAb, and TBII over 10 years in 34 TSBAb-positives with hypothyroidism and in 98 TSAb-positives with hyperthyroidism. Half of the 34 TSBAb-positives with hypothyroidism continued to have persistently positive TSBAb, continued to have hypothyroidism, and did not recover from hypothyroidism. Ten of the 98 TSAb-positives with hyperthyroidism continued to have positive TSAb and continued to have hyperthyroidism. TSBAb had disappeared in 15 of the 34 TSBAb-positives with hypothyroidism. With the disappearance of TSBAb, recovery from hypothyroidism was noted in 13 (87%) of the 15 patients. TSAb had disappeared in 73 of the 98 TSAb-positives with hyperthyroidism. With the disappearance of TSAb, remissions of hyperthyroidism were noted in 60 (82%) of the 73. Two of the 34 TSBAb-positives with hypothyroidism developed TSAb-positive Graves’ hyperthyroidism. Two of the 98 TSAb-positive Graves’ patients with hyperthyroidism developed TSBAb-positive hypothyroidism. TSBAb and TSAb are TRAbs. TSBAb-hypothyroidism and TSAb-hyperthyroidism may be two aspects of one disease (TRAb disease). Two forms of autoimmune thyroiditis: atrophic and goitrous. We followed 34 TSBAb-positive patients with hypothyroidism (24 atrophic and 10 goitrous) over 10 years. All of the 10 TSBAb-positive goitrous patients recovered from hypothyroidism and 19 (79%) of the 24 TSBAb-positive atrophic patients continued to have hypothyroidism.
Histopathologic Overlap between Fibrosing Mediastinitis and IgG4-Related Disease
Authors: Peikert Tobias , Shrestha Bijayee , Aubry Marie Christine , Colby Thomas V. , Ryu Jay H. , Sekiguchi Hiroshi , Smyrk Thomas C. , Specks Ulrich , Yi Eunhee S.
Published: May 2012

Fibrosing mediastinitis (FM) and IgG4-related disease (IgG4-RD) are two fibroinflammatory disorders with potentially overlapping clinical and radiological features. In this paper, we looked for histopathologic features of IgG4-RD and enumerated infiltrating IgG4-positive plasma cells within mediastinal tissue biopsies from FM patients. We identified 15 consecutive FM surgical mediastinal tissue biopsies between 1985 and 2006. All patients satisfied the clinical and radiological diagnostic criteria for FM. All patients had either serological or radiological evidence of prior histoplasmosis or granulomatous disease, respectively. Formalin-fixed paraffin-embedded tissue sections of all patients were stained for H&E, IgG, and IgG4. Three samples met the predefined diagnostic criteria for IgG4-RD. In addition, characteristic histopathologic changes of IgG4-RD in the absence of diagnostic numbers of tissue infiltrating IgG4-positive plasma cells were seen in a number of additional cases (storiform cell-rich fibrosis in 11 cases, lymphoplasmacytic infiltrate in 7 cases, and obliterative phlebitis/arteritis in 2 cases). We conclude that up to one-third of histoplasmosis or granulomatous-disease-associated FM cases demonstrate histopathological features of IgG4-RD spectrum. Whether these changes occur as the host immune response against Histoplasma or represent a manifestation of IgG4-RD remains to be determined. Studies to prospectively identify these cases and evaluate their therapeutic responses to glucocorticoids and/or other immunosuppressive agents such as rituximab are warranted.
MAP1B Interaction with the FW Domain of the Autophagic Receptor Nbr1 Facilitates Its Association to the Microtubule Network
Authors: Marchbank Katie , Waters Sarah , Roberts Roland G. , Solomon Ellen , Whitehouse Caroline A.
Published: May 2012

Selective autophagy is a process whereby specific targeted cargo proteins, aggregates, or organelles are sequestered into double-membrane-bound phagophores before fusion with the lysosome for protein degradation. It has been demonstrated that the microtubule network is important for the formation and movement of autophagosomes. Nbr1 is a selective cargo receptor that through its interaction with LC3 recruits ubiquitinated proteins for autophagic degradation. This study demonstrates an interaction between the evolutionarily conserved FW domain of Nbr1 with the microtubule-associated protein MAP1B. Upon autophagy induction, MAP1B localisation is focused into discrete vesicles with Nbr1. This colocalisation is dependent upon an intact microtubule network as depolymerisation by nocodazole treatment abolishes starvation-induced MAP1B recruitment to these vesicles. MAP1B is not recruited to autophagosomes for protein degradation as blockage of lysosomal acidification does not result in significant increased MAP1B protein levels. However, the protein levels of phosphorylated MAP1B are significantly increased upon blockage of autophagic degradation. This is the first evidence that links the ubiquitin receptor Nbr1, which shuttles ubiquitinated proteins to be degraded by autophagy, to the microtubule network.
Effects of Gravity and Inlet Location on a Two-Phase Countercurrent Imbibition in Porous Media
Authors: El-Amin M. F. , Salama Amgad , Sun Shuyu
Published: May 2012

We introduce a numerical investigation of the effect of gravity on the problem of two-phase countercurrent imbibition in porous media. We consider three cases of inlet location, namely, from, side, top, and bottom. A 2D rectangular domain is considered for numerical simulation. The results indicate that gravity has a significant effect depending on open-boundary location.
Protective Role ofPhyllanthus niruriExtract against Thioacetamide-Induced Liver Cirrhosis in Rat Model
Authors: Amin Zahra A. , Bilgen Mehmet , Alshawsh Mohammed A. , Ali Hapipah M. , Hadi A. Hamid A. , Abdulla Mahmood A.
Published: May 2012

A preclinical study was performed to determine if the extract fromPhyllanthus niruri(PN) plays a protective role against liver cirrhosis induced by thioacetamide (TAA) in rats. Initially, acute toxicity was tested and the results showed that the extract was benign when applied to healthy rats. Next, the therapeutic effect of the extract was investigated using five groups of rats: control, TAA, silymarin, and PN high dose and low dose groups. Significant differences were observed between the TAA group and the other groups regarding body and liver weights, liver biochemical parameters, total antioxidant capacity, lipid peroxidation, and oxidative stress enzyme levels. Gross visualization indicated coarse granules on the surface of the hepatotoxic rats’ livers, in contrast to the smoother surface in the livers of the silymarin and PN-treated rats. Histopathological analysis revealed necrosis, lymphocytes infiltration in the centrilobular region, and fibrous connective tissue proliferation in the livers of the hepatotoxic rats. But, the livers of the treated rats had comparatively minimal inflammation and normal lobular architecture. Silymarin and PN treatments effectively restored these measurements closer to their normal levels. Progression of liver cirrhosis induced by TAA in rats can be intervened using the PN extract and these effects are comparable to those of silymarin.
Viscoelastic Properties of Mineral-Filled Poly(lactic acid) Composites
Authors: Gregorova Adriana , Machovsky Michal , Wimmer Rupert
Published: May 2012

Poly(lactic acid) was filled with 20 wt% of the three mineral fillers Mica, Zeolite, and Vansil, differing in the particle shape and surface area. Viscoelastic properties of unfilled and filled composites were investigated via dynamic mechanical analysis, while filler and fracture surface morphology of the composites was analysed through scanning electron microscopy. Results demonstrate the relationships between viscoelastic damping behaviour of filled PLA composites and the filler distribution in the PLA matrix. Both damping reduction and scanning electron microscope analysis revealed that Zeolite was better distributed in the poly(lactic acid) matrix than the other used fillers Mica and Vansil. The interfacial filler/matrix adhesion has again proved to be the key factor determining thermal and mechanical properties of reinforced composite material.
Inhibition ofNO2,PGE2, TNF-α,andiNOS EXpression byShorea robustaL.: An Ethnomedicine Used for Anti-Inflammatory and Analgesic Activity
Authors: Debprasad Chattopadhyay , Hemanta Mukherjee , Paromita Bag , Durbadal Ojha , Kumar Konreddy Ananda , Shanta Dutta , Kumar Haldar Pallab , Tapan Chatterjee , Ashoke Sharon , Sekhar Chakraborti
Published: May 2012

This paper is an attempt to evaluate the anti-inflammatory and analgesic activities and the possible mechanism of action of tender leaf extracts ofShorea robusta, traditionally used in ailments related to inflammation. The acetic-acid-induced writhing and tail flick tests were carried out for analgesic activity, while the anti-inflammatory activity was evaluated in carrageenan-and dextran- induced paw edema and cotton-pellet-induced granuloma model. The acetic-acid-induced vascular permeability, erythrocyte membrane stabilization, release of proinflammatory mediators (nitric oxide and prostaglandin E2), and cytokines (tumor necrosis factor-α, and interleukins-1β and -6) from lipopolysaccharide-stimulated human monocytic cell lines were assessed to understand the mechanism of action. The results revealed that both aqueous and methanol extract (400 mg/kg) caused significant reduction of writhing and tail flick, paw edema, granuloma tissue formation (P<0.01), vascular permeability, and membrane stabilization. Interestingly, the aqueous extract at 40 μg/mL significantly inhibited the production of NO and release of PGE2, TNF-α, IL-1β, and IL-6. Chemically the extract contains flavonoids and triterpenes and toxicity study showed that the extract is safe. Thus, our study validated the scientific rationale of ethnomedicinal use ofS. robustaand unveils its mechanism of action. However, chronic toxicological studies with active constituents are needed before its use.
Normed Ordered and -Metric Spaces
Authors: Al-Rawashdeh Ahmed , Shatanawi Wasfi , Khandaqji Muna
Published: May 2012

In 2007, Haung and Zhang introduced the notion of cone metric spaces. In this paper, we define an ordered space , and we discuss some properties and examples. Also, normed ordered space is introduced. We recall properties of , and we discuss their extension to . We introduce the notion of -metric spaces and characterize cone metric space. Afterwards, we get generalizations of notions of convergence and Cauchy theory. In particular, we get a fixed point theorem of a contractive mapping in -metric spaces. Finally, by extending the notion of a contractive sequence in a real-valued metric space, we show that in -metric spaces, a contractive sequence is Cauchy.
The Human Tripeptide GHK-Cu in Prevention of Oxidative Stress and Degenerative Conditions of Aging: Implications for Cognitive Health
Authors: Pickart Loren , Vasquez-Soltero Jessica Michelle , Margolina Anna
Published: May 2012

Oxidative stress, disrupted copper homeostasis, and neuroinflammation due to overproduction of proinflammatory cytokines are considered leading causative factors in development of age-associated neurodegenerative conditions. Recently, a new mechanism of aging—detrimental epigenetic modifications—has emerged. Thus, compounds that possess antioxidant, anti-inflammatory activity as well as compounds capable of restoring copper balance and proper gene functioning may be able to prevent age-associated cognitive decline and ward off many common neurodegenerative conditions. The aim of this paper is to bring attention to a compound with a long history of safe use in wound healing and antiaging skin care. The human tripeptide GHK was discovered in 1973 as an activity in human albumin that caused old human liver tissue to synthesize proteins like younger tissue. It has high affinity for copper ions and easily forms a copper complex or GHK-Cu. In addition, GHK possesses a plethora of other regenerative and protective actions including antioxidant, anti-inflammatory, and wound healing properties. Recent studies revealed its ability to up- and downregulate a large number of human genes including those that are critical for neuronal development and maintenance. We propose GHK tripeptide as a possible therapeutic agent against age-associated neurodegeneration and cognitive decline.
Predicting Disease Onset from Mutation Status Using Proband and Relative Data with Applications to Huntington's Disease
Authors: Chen Tianle , Wang Yuanjia , Ma Yanyuan , Marder Karen , Langbehn Douglas R.
Published: May 2012

Huntington's disease (HD) is a progressive neurodegenerative disorder caused by an expansion of CAG repeats in the IT15 gene. The age-at-onset (AAO) of HD is inversely related to the CAG repeat length and the minimum length thought to cause HD is 36. Accurate estimation of the AAO distribution based on CAG repeat length is important for genetic counseling and the design of clinical trials. In the Cooperative Huntington's Observational Research Trial (COHORT) study, the CAG repeat length is known for the proband participants. However, whether a family member shares the huntingtin gene status (CAG expanded or not) with the proband is unknown. In this work, we use the expectation-maximization (EM) algorithm to handle the missing huntingtin gene information in first-degree family members in COHORT, assuming that a family member has the same CAG length as the proband if the family member carries a huntingtin gene mutation. We perform simulation studies to examine performance of the proposed method and apply the methods to analyze COHORT proband and family combined data. Our analyses reveal that the estimated cumulative risk of HD symptom onset obtained from the combined data is slightly lower than the risk estimated from the proband data alone.
Cross-Border Quest: The Reality and Legality of Transplant Tourism
Authors: Ambagtsheer Frederike , Zaitch Damián , van Swaaningen René , Duijst Wilma , Zuidema Willij , Weimar Willem
Published: May 2012

Background.Transplant tourism is a phenomenon where patients travel abroad to purchase organs for transplants. This paper presents the results of a fieldwork study by describing the experiences of Dutch transplant professionals confronted by patients who allegedly purchased kidney transplants abroad. Second, it addresses the legal definition and prohibition of transplant tourism under national and international law. The final part addresses the legal implications of transplant tourism for patients and physicians.Methods.The study involved seventeen interviews among transplant physicians, transplant coordinators and policy-experts and a review of national and international legislation that prohibit transplant tourism.Results.All Dutch transplant centers are confronted with patients who undergo transplants abroad. The estimated total number is four per year. Transplant tourism is not explicitly defined under national and international law. While the purchase of organs is almost universally prohibited, transplant tourism is hardly punishable because national laws generally do not apply to crimes committed abroad. Moreover, the purchase of organs (abroad) is almost impossible to prove.Conclusions.Transplant tourism is a legally complex phenomenon that warrants closer research and dialogue. The legal rights and obligations of patients and physicians confronted with transplant tourism should be clarified.