Vascular Reactivity in Newly-Formed and Mature Arterialized Collateral Capillaries

Peripheral arterial occlusive disease (PAOD) is a globally-prevalent cardiovascular disease in which atherosclerotic plaques narrow arterial lumen diameters and restrict blood flow to downstream tissues. The impact of these occlusions can be mitigated by collateral vessels that connect parallel arterial branches and act as natural bypasses to maintain perfusion. In animal models that lack collateral arterioles, capillaries that connect terminal arteriolar segments can arterialize and form functional collaterals following an ischemic event; however, in the early stages of development, vasodilation is impaired. We explored the mechanism of impaired vasodilation in arterialized collateral capillaries (ACCs) and pre-existing collaterals (PECs) by evaluating endothelial-dependent vasodilation and endothelial-independent reactivity at day seven following the ischemic event. We also evaluated functional vasodilation in mature ACCs and PECs at day 21 by applying vasodilation inhibitors during the electrical stimulation of muscle contraction. Arterial occlusion was performed by ligating the cranial-lateral spinotrapezius feed artery in Balb/C mice, a strain that either lacks native arteriolar collaterals or contains a single collateral arteriole (~50% of mice), as opposed to the C57Bl/6 strain, which each contain 10 or more collateral arterioles. At seven days post-surgery, both vasodilation and vasoconstriction were impaired in ACCs when compared to terminal arterioles of similar size in unoperated limbs, but still exhibited significant changes when compared to baseline. The comparable reactivity in both endothelial-dependent and independent vasodilation at day-seven in ACCs indicates that vascular smooth muscle cells are likely responsible for the impairment, as they may still be developing, rearranging, or both, and are not yet fully capable of regulating diameter in immature ACCs. However, by 21 days post-ligation, ACCs regained the capacity to dilate in response to muscle contraction, and utilized similar vasodilation pathways as control vessels. At seven days post-ligation, PECs had impaired endothelialindependent dilation, but successful endothelial-dependent dilation, indicating the use of alternative pathways to dilate. Unlike ACCs, the PECs never completely restored vasodilation capabilities by day 21, which may be due to a variation in smooth muscle phenotype, sensitivity to vasoactive agents, and/or limited growth factor expression. For future work, evaluating collateral formation and vasodilation in a diseased model and investigating molecular variations in the smooth muscle may yield additional knowledge that can improve therapies for patients during ischemic events

Investigation of Optimal Approaches to Assessing the Megacity Innovative Potential

The authors of the article set a goal to identify the most accurate and economical methods for assessing the innovative potential of megacity in terms of the used resources. For that purpose, methods were selected, calculations were carried out for two of them, which were suitable for the goal and described in detail in the methodological literature. The results of two other methods presented in the public domain for comparable periods of time for three selected regions were used. The study used materials from Russian and foreign sources. Based on the results of the work done, certain conclusions were made that allow a more accurate selection of methods for assessing the innovative potential of cities, considering the objectives of such an assessment, as well as the resource availability of a group of researchers. A critical view is also presented on the further application of all methods, which requires researchers of the local innovation potential to have the accuracy, objectivity in assessments, and independence in their interpretation

Evidence for length-dependent wire expansion, filament dedensification and consequent degradation of critical current density in Ag-alloy sheathed Bi-2212 wires

It is well known that longer Bi-2212 conductors have significantly lower critical current density (Jc) than shorter ones, and recently it has become clear that a major cause of this reduction is internal gas pressure generated during heat treatment, which expands the wire diameter and dedensifies the Bi-2212 filaments. Here we report on the length-dependent expansion of 5 to 240 cm lengths of state-of-the-art, commercial Ag alloy-sheathed Bi-2212 wire after full and some partial heat treatments. Detailed image analysis along the wire length shows that the wire diameter increases with distance from the ends, longer samples often showing evident damage and leaks provoked by the internal gas pressure. Comparison of heat treatments carried out just below the melting point and with the usual melt process makes it clear that melting is crucial to developing high internal pressure. The decay of Jc away from the ends is directly correlated to the local wire diameter increase, which decreases the local Bi-2212 filament mass density and lowers Jc, often by well over 50%. It is clear that control of the internal gas pressure is crucial to attaining the full Jc of these very promising round wires and that the very variable properties of Bi-2212 wires are due to the fact that this internal gas pressure has so far not been well controlled

Reduction of gas bubbles and improved critical current density in Bi-2212 round wire by swaging

Bi-2212 round wire is made by the powder-in-tube technique. An unavoidable property of powder-in-tube conductors is that there is about 30% void space in the as-drawn wire. We have recently shown that the gas present in the as-drawn Bi-2212 wire agglomerates into large bubbles and that they are presently the most deleterious current limiting mechanism. By densifying short 2212 wires before reaction through cold isostatic pressing (CIPping), the void space was almost removed and the gas bubble density was reduced significantly, resulting in a doubled engineering critical current density (JE) of 810 A/mm2 at 5 T, 4.2 K. Here we report on densifying Bi-2212 wire by swaging, which increased JE (4.2 K, 5 T) from 486 A/mm2 for as-drawn wire to 808 A/mm2 for swaged wire. This result further confirms that enhancing the filament packing density is of great importance for making major JE improvement in this round-wire magnet conductor.Comment: To be published in IEEE Transactions on Applied Superconductivity, 23, xxxxxx (2013

Platelet-derived growth factor receptor-β, carrying the activating mutation D849N, accelerates the establishment of B16 melanoma

<p>Abstract</p> <p>Background</p> <p>Platelet-derived growth factor (PDGF)-BB and PDGF receptor (PDGFR)-β are mainly expressed in the developing vasculature, where PDGF-BB is produced by endothelial cells and PDGFR-β is expressed by mural cells, including pericytes. PDGF-BB is produced by most types of solid tumors, and PDGF receptor signaling participates in various processes, including autocrine stimulation of tumor cell growth, recruitment of tumor stroma fibroblasts, and stimulation of tumor angiogenesis. Furthermore, PDGF-BB-producing tumors are characterized by increased pericyte abundance and accelerated tumor growth. Thus, there is a growing interest in the development of tumor treatment strategies by blocking PDGF/PDGFR function. We have recently generated a mouse model carrying an activated PDGFR-β by replacing the highly conserved aspartic acid residue (D) 849 in the activating loop with asparagine (N). This allowed us to investigate, in an orthotopic tumor model, the role of increased stromal PDGFR-β signaling in tumor-stroma interactions.</p> <p>Methods</p> <p>B16 melanoma cells lacking PDGFR-β expression and either mock-transfected or engineered to express PDGF-BB, were injected alone or in combination with matrigel into mice carrying the activated PDGFR-β (D849N) and into wild type mice. The tumor growth rate was followed and the vessel status of tumors, i.e. total vessel area/tumor, average vessel surface and pericyte density of vessels, was analyzed after resection.</p> <p>Results</p> <p>Tumors grown in mice carrying an activated PDGFR-β were established earlier than those in wild-type mice. In this early phase, the total vessel area and the average vessel surface were higher in tumors grown in mice carrying the activated PDGFR-β (D849N) compared to wild-type mice, whereas we did not find a significant difference in the number of tumor vessels and the pericyte abundance around tumor vessels between wild type and mutant mice. At later phases of tumor progression, no significant difference in tumor growth rate was observed between wild type mice and mutant mice, although the pericyte coverage was higher around tumor vessels from mutant mice.</p> <p>Conclusion</p> <p>Our findings suggest that the activated PDGFR-β (D849N) in the host animal increased the total vessel area and the average vessel surface even in PDGF-negative tumors, resulting in a shorter lag phase during tumor establishment.</p

Retail returns management strategy: An alignment perspective

This research aims to shed light on the formulation of returns management strategies and to identify key returns management components in developing more effective returns management strategies. Anchored in supply chain orientation and supply chain alignment research, we use a multiple confirmatory case study of six retailers operating in online commerce. Interviews with fifteen managers provided the primary empirical data source for the study. The results confirm the presence of alignment in establishing effective strategies for managing product returns and suggest a return policy. The findings provide detailed insights into seven existing misalignments that curb the strength of alignment. These serve as strategic elements for managers to consider in formulating returns management strategies and goals. The results may assist retail and supply chain professionals in their quest to develop effective strategies for managing product returns. Research on returns management strategy is scarce. This study offers a conceptual framework and provides new empirical insights into returns management strategy formulation and, in particular, potential misalignments

The World Heritage Naracoorte Caves beyond 500 ka: U-Pb dating and charcoal analysis from speleothems with implications for Pleistocene vertebrate fossil deposits

Session CL1.19Under the current rapid global warming, studying how environments responded to past climate change becomes increasingly important to better understand what impact climate variability has on regional flora and fauna. Our new multi-proxy study to the World Heritage Naracoorte Caves in southern Australia provides a unique window into the past climate as they are heavily decorated with speleothems but also contain in-fill deposits rich in Pleistocene vertebrate fossils including the extinct Australian megafauna. Until now, these speleothems have been dated using U-Th series and the fossil-bearing sediments with Optical Stimulated Luminescence and Electro Spin Resonance techniques, but only up to ca. 500 ka. We have U-Pb dated speleothems from the Naracoorte Caves for the first time and extended the record beyond 500 ka. We combined precise chronology with analyses of pollen and charcoal within the speleothems which allows us to better understand how southern Australia’s climate and its vegetation changed during the Quaternary. It also provides a unique insight into the timing and extent of cave opening with important potential for much older vertebrate fossil deposits than previously thought.Rieneke Weij, Jon Woodhead, Liz Reed, Kale Sniderman, John Hellstrom, and Russell Drysdal

Strongly linked current flow in polycrystalline forms of the new superconductor MgB2

The discovery of superconductivity at 39 K in MgB2[1] raises many issues. One of the central questions is whether this new superconductor resembles a high-temperature-cuprate superconductor or a low-temperature metallic superconductor in terms of its current carrying characteristics in applied magnetic fields. In spite of the very high transition temperatures of the cuprate superconductors, their performance in magnetic fields has several drawbacks[2]. Their large anisotropy restricts high bulk current densities to much less than the full magnetic field-temperature (H-T) space over which superconductivity is found. Further, weak coupling across grain boundaries makes transport current densities in untextured polycrystalline forms low and strongly magnetic field sensitive[3,4]. These studies of MgB2 address both issues. In spite of the multi-phase, untextured, nano-scale sub-divided nature of our samples, supercurrents flow throughout without the strong sensitivity to weak magnetic fields characteristic of Josephson-coupled grains[3]. Magnetization measurements over nearly all of the superconducting H-T plane show good temperature scaling of the flux pinning force, suggestive of a current density determined by flux pinning. At least two length scales are suggested by the magnetization and magneto optical (MO) analysis but the cause of this seems to be phase inhomogeneity, porosity, and minority insulating phase such as MgO rather than by weakly coupled grain boundaries. Our results suggest that polycrystalline ceramics of this new class of superconductor will not be compromised by the weak link problems of the high temperature superconductors, a conclusion with enormous significance for applications if higher temperature analogs of this compound can be discovered

Very high upper critical fields in MgB2 produced by selective tuning of impurity scattering

We report a significant enhancement of the upper critical field $H_{c2}$ of different $MgB_2$ samples alloyed with nonmagnetic impurities. By studying films and bulk polycrystals with different resistivities $\rho$, we show a clear trend of $H_{c2}$ increase as $\rho$ increases. One particular high resistivity film had zero-temperature $H_{c2}(0)$ well above the $H_{c2}$ values of competing non-cuprate superconductors such as $Nb_3Sn$ and Nb-Ti. Our high-field transport measurements give record values $H_{c2}^\perp (0) \approx 34T$ and $H_{c2}\|(0) \approx 49 T$ for high resistivity films and $H_{c2}(0)\approx 29 T$ for untextured bulk polycrystals. The highest $H_{c2}$ film also exhibits a significant upward curvature of $H_{c2}(T)$, and temperature dependence of the anisotropy parameter $\gamma(T) = H_{c2}\|/ H_{c2}^\perp$ opposite to that of single crystals: $\gamma(T)$ decreases as the temperature decreases, from $\gamma(T_c) \approx 2$ to $\gamma(0) \approx 1.5$. This remarkable $H_{c2}$ enhancement and its anomalous temperature dependence are a consequence of the two-gap superconductivity in $MgB_2$, which offers special opportunities for further $H_{c2}$ increase by tuning of the impurity scattering by selective alloying on Mg and B sites. Our experimental results can be explained by a theory of two-gap superconductivity in the dirty limit. The very high values of $H_{c2}(T)$ observed suggest that $MgB_2$ can be made into a versatile, competitive high-field superconductor.Comment: An updated version of the paper (12/12/2002)that was placed on cond-mat on May 7 200