A URI-based approach for addressing fragments of media resources on the Web

To make media resources a prime citizen on the Web, we have to go beyond simply replicating digital media files. The Web is based on hyperlinks between Web resources, and that includes hyperlinking out of resources (e.g., from a word or an image within a Web page) as well as hyperlinking into resources (e.g., fragment URIs into Web pages). To turn video and audio into hypervideo and hyperaudio, we need to enable hyperlinking into and out of them. The W3C Media Fragments Working Group is taking on the challenge to further embrace W3C??s mission to lead the World Wide Web to its full potential by developing a Media Fragment protocol and guidelines that ensure the long-term growth of the Web. The major contribution of this paper is the introduction of Media Fragments as a media-format independent, standard means of addressing media resources using URIs. Moreover, we explain how the HTTP protocol can be used and extended to serve Media Fragments and what the impact is for current Web-enabled media formats.     

An exploratory study of the impact of antipatterns on class change- and fault-proneness

Antipatterns are poor design choices that are conjectured to make object-oriented systems harder to maintain. We investigate the impact of antipatterns on classes in object-oriented systems by studying the relation between the presence of antipatterns and the change- and fault-proneness of the classes. We detect 13 antipatterns in 54 releases of ArgoUML, Eclipse, Mylyn, and Rhino, and analyse (1) to what extent classes participating in antipatterns have higher odds to change or to be subject to fault-fixing than other classes, (2) to what extent these odds (if higher) are due to the sizes of the classes or to the presence of antipatterns, and (3) what kinds of changes affect classes participating in antipatterns. We show that, in almost all releases of the four systems, classes participating in antipatterns are more change-and fault-prone than others. We also show that size alone cannot explain the higher odds of classes with antipatterns to underwent a (fault-fixing) change than other classes. Finally, we show that structural changes affect more classes with antipatterns than others. We provide qualitative explanations of the increase of change- and fault-proneness in classes participating in antipatterns using release notes and bug reports. The obtained results justify a posteriori previous work on the specification and detection of antipatterns and could help to better focus quality assurance and testing activities.     

Oxidative dimerisation of propene to 1,5-hexadiene on Bi-Zn-O catalysts

The oxidative dimerisation of propene to 1,5-hexadiene has been investigated on Bi-Zn-O catalysts. The Bi₄₈ZnO₇₃ phase, observed in the catalysts calcined at 700 ° C is an active and selective catalyst for the formation of 1,5-hexadiene. The best catalytic performance (1,5-hexadiene selectivity 64%) has been obtained at 525 ° C, with a propene to oxygen ratio of 26, on a catalyst formed by Bi₄₈ZnO₇₃ with a small excess of ZnO.     

Electrical properties of monoazacrown ether-substituted phthalocyanines

D.c. conductivities of polycrystalline monoazacrown ether-substituted phthalocyanines (M=2H, Ni, Zn, Pb, Cu) and diphthalocyanine (M=Lu) are measured as Au-MPc-Au sandwiches to be of the order 10^–10–10^–12 S m^–1. Chemical doping with oxidants (e.g. NOBF₄) and enhancing the stacking of planar phthalocyanine moieties through the formation of alkali metal adducts with sodium and potassium ions leads to increase in conductivity of the order 10¹–10². The low conductivity and the diamagneticity of the bis(phthalocyaninato)-lutetium can be ascribed to the lack of radical nature in LuH(Pc)₂. For the a.c. conductivities, lead and lutetium complexes form a group with higher conductivities and the rest show lower conductivity. The conduction activation energies calculated from Arrhenius plots exhibit the lowest value (0.40 eV) for the lutetium compound.Part of this work was presented at NATO-ASI on Semiconductor Materials and Processing Technologies, Erice, Sicily, 1–13 July 1991.     

Particular behavior of spindle thermal deformation by thermal bending

Thermally induced errors reduce the accuracy in precision machining, and a great deal of research has been presented on compensation for these errors in machine tools. However, during the transition period after commencing or stopping spindle rotation, thermal deformation behavior is very complex. In particular, the y-directional movement of the vertical machining center cannot be explained by thermal expansion alone because of the relationship between deformation and temperature. Thermal bending that is generated from the thermal gradient in the structure causes this movement. In the research described in this paper, a theoretical explanation and an experimental verification is given for the particular behavior of spindle thermal deformation. As it is not easy to map the relationship of the compensation model, separation of the steady from the non-steady state in the mapping process is strongly recommended.     

Qualitative and Quantitative Comparison of Plasma Exosomes from Neonates and Adults

Exosomes are extracellular vesicles that contain nucleic acids, lipids and metabolites, and play a critical role in health and disease as mediators of intercellular communication. The majority of extracellular vesicles in the blood are platelet-derived. Compared to adults, neonatal platelets are hyporeactive and show impaired granule release, associated with defects in Soluble N-ethylmaleimide-sensitive fusion Attachment protein REceptor (SNARE) proteins. Since these proteins participate in biogenesis of exosomes, we investigated the potential differences between newborn and adult plasma-derived exosomes. Plasma-derived exosomes were isolated by ultracentrifugation of umbilical cord blood from full-term neonates or peripheral blood from adults. Exosome characterization included size determination by transmission electron microscopy and quantitative proteomic analysis. Plasma-derived exosomes from neonates were significantly smaller and contained 65% less protein than those from adults. Remarkably, 131 proteins were found to be differentially expressed, 83 overexpressed and 48 underexpressed in neonatal (vs. adult) exosomes. Whereas the upregulated proteins in plasma exosomes from neonates are associated with platelet activation, coagulation and granule secretion, most of the underexpressed proteins are immunoglobulins. This is the first study showing that exosome size and content change with age. Our findings may contribute to elucidating the potential “developmental hemostatic mismatch risk” associated with transfusions containing plasma exosomes from adults.     

Applications of Mesenchymal Stem Cells in Skin Regeneration and Rejuvenation

Mesenchymal stem cells (MSCs) are multipotent stem cells derived from adult stem cells. Primary MSCs can be obtained from diverse sources, including bone marrow, adipose tissue, and umbilical cord blood. Recently, MSCs have been recognized as therapeutic agents for skin regeneration and rejuvenation. The skin can be damaged by wounds, caused by cutting or breaking of the tissue, and burns. Moreover, skin aging is a process that occurs naturally but can be worsened by environmental pollution, exposure to ultraviolet radiation, alcohol consumption, tobacco use, and undernourishment. MSCs have healing capacities that can be applied in damaged and aged skin. In skin regeneration, MSCs increase cell proliferation and neovascularization, and decrease inflammation in skin injury lesions. In skin rejuvenation, MSCs lead to production of collagen and elastic fibers, inhibition of metalloproteinase activation, and promote protection from ultraviolet radiation-induced senescence. In this review, we focus on how MSCs and MSC-derived molecules improve diseased and aged skin. Additionally, we emphasize that induced pluripotent stem cell (iPSC)-derived MSCs are potentially advanced MSCs, which are suitable for cell therapy.     

Pharmacological Evidence on Augmented Antiallodynia Following Systemic Co-Treatment with GlyT-1 and GlyT-2 Inhibitors in Rat Neuropathic Pain Model

The limited effect of current medications on neuropathic pain (NP) has initiated large efforts to develop effective treatments. Animal studies showed that glycine transporter (GlyT) inhibitors are promising analgesics in NP, though concerns regarding adverse effects were raised. We aimed to study NFPS and Org-25543, GlyT-1 and GlyT-2 inhibitors, respectively and their combination in rat mononeuropathic pain evoked by partial sciatic nerve ligation. Cerebrospinal fluid (CSF) glycine content was also determined by capillary electrophoresis. Subcutaneous (s.c.) 4 mg/kg NFPS or Org-25543 showed analgesia following acute administration (30–60 min). Small doses of each compound failed to produce antiallodynia up to 180 min after the acute administration. However, NFPS (1 mg/kg) produced antiallodynia after four days of treatment. Co-treatment with subanalgesic doses of NFPS (1 mg/kg) and Org-25543 (2 mg/kg) produced analgesia at 60 min and thereafter meanwhile increased significantly the CSF glycine content. This combination alleviated NP without affecting motor function. Test compounds failed to activate G-proteins in spinal cord. To the best of our knowledge for the first time we demonstrated augmented analgesia by combining GlyT-1 and 2 inhibitors. Increased CSF glycine content supports involvement of glycinergic system. Combining selective GlyT inhibitors or developing non-selective GlyT inhibitors might have therapeutic value in NP.     

Novel (Phenothiazinyl)Vinyl-Pyridinium Dyes and Their Potential Applications as Cellular Staining Agents

We report here the synthesis and structural characterization of novel cationic (phenothiazinyl)vinyl-pyridinium (PVP) dyes, together with optical (absorption/emission) properties and their potential applicability as fluorescent labels. Convective heating, ultrasound irradiation and mechanochemical synthesis were considered as alternative synthetic methodologies proficient for overcoming drawbacks such as long reaction time, nonsatisfactory yields or solvent requirements in the synthesis of novel dye (E)-1-(3-chloropropyl)-4-(2-(10-methyl-10H-phenothiazin-3-yl)vinyl)pyridin-1-ium bromide 3d and its N-alkyl-2-methylpyridinium precursor 1c. The trans geometry of the newly synthesized (E)-4-(2-(7-bromo-10-ethyl-10H-phenothiazin-3-yl)vinyl)-1-methylpyridin-1-ium iodide 3b and (E)-1-methyl-4-(2-(10-methyl-10H-phenothiazin-3-yl)vinyl)pyridin-1-ium tetrafluoroborate 3a′ was confirmed by single crystal X-ray diffraction. A negative solvatochromism of the dyes in polar solvents was highlighted by UV-Vis spectroscopy and explanatory insights were supported by molecular modeling which suggested a better stabilization of the lowest unoccupied molecular orbitals (LUMO). The photostability of the dye 3b was investigated by irradiation at 365 nm in different solvents, while the steady-state and time-resolved fluorescence properties of dye 3b and 3a′ in solid state were evaluated under one-photon excitation at 485 nm. The in vitro cytotoxicity of the new PVP dyes on B16-F10 melanoma cells was evaluated by WST-1 assay, while their intracellular localization was assessed by epi-fluorescence conventional microscopy imaging as well as one- and two-photon excited confocal fluorescence lifetime imaging microscopy (FLIM). PVP dyes displayed low cytotoxicity, good internalization inside melanoma cells and intense fluorescence emission inside the B16-F10 murine melanoma cells, making them suitable staining agents for imaging applications.     

SUL-151 Decreases Airway Neutrophilia as a Prophylactic and Therapeutic Treatment in Mice after Cigarette Smoke Exposure

Chronic obstructive pulmonary disease (COPD) caused by cigarette smoke (CS) is featured by oxidative stress and chronic inflammation. Due to the poor efficacy of standard glucocorticoid therapy, new treatments are required. Here, we investigated whether the novel compound SUL-151 with mitoprotective properties can be used as a prophylactic and therapeutic treatment in a murine CS-induced inflammation model. SUL-151 (4 mg/kg), budesonide (500 μg/kg), or vehicle were administered via oropharyngeal instillation in this prophylactic and therapeutic treatment setting. The number of immune cells was determined in the bronchoalveolar lavage fluid (BALF). Oxidative stress response, mitochondrial adenosine triphosphate (ATP) production, and mitophagy-related proteins were measured in lung homogenates. SUL-151 significantly decreased more than 70% and 50% of CS-induced neutrophils in BALF after prophylactic and therapeutic administration, while budesonide showed no significant reduction in neutrophils. Moreover, SUL-151 prevented the CS-induced decrease in ATP and mitochondrial mtDNA and an increase in putative protein kinase 1 expression in the lung homogenates. The concentration of SUL-151 was significantly correlated with malondialdehyde level and radical scavenging activity in the lungs. SUL-151 inhibited the increased pulmonary inflammation and mitochondrial dysfunction in this CS-induced inflammation model, which implied that SUL-151 might be a promising candidate for COPD treatment.