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Redox state sustained by reactive oxygen species (ROS) is crucial for regeneration; however, the interplay between oxygen (O2), ROS and hypoxia-inducible factors (HIF) remains elusive. Here we observe, using an optic-based probe (optrode), an elevated and steady O2 influx immediately upon amputation. The spatiotemporal O2 influx profile correlates with the regeneration of Xenopus laevis tadpole tails. Inhibition of ROS production but not ROS scavenging decreases O2 influx. Inhibition of HIF-1α impairs regeneration and stabilization of HIF-1α induces regeneration in the refractory period. In the regeneration bud, hypoxia correlates with O2 influx, ROS production, and HIF-1α stabilization that modulate regeneration. Further analyses reveal that heat shock protein 90 is a putative downstream target of HIF-1α while electric current reversal is a de facto downstream target of HIF-1α. Collectively, the results show a mechanism for regeneration via the orchestration of O2 influx, ROS production, and HIF-1α stabilization.

Weak electric fields guide cell migration, known as galvanotaxis/electrotaxis. The sensor(s) cells use to detect the fields remain elusive. Here, we perform a large-scale screen using an RNAi library targeting ion transporters in human cells. We identify 18 genes that show either defective or increased galvanotaxis after knockdown. Knockdown of the KCNJ15 gene (encoding inwardly rectifying K+ channel Kir4.2) specifically abolishes galvanotaxis, without affecting basal motility and directional migration in a monolayer scratch assay. Depletion of cytoplasmic polyamines, highly positively charged small molecules that regulate Kir4.2 function, completely inhibits galvanotaxis, whereas increase of intracellular polyamines enhances galvanotaxis in a Kir4.2-dependent manner. Expression of a polyamine binding-defective mutant of KCNJ15 significantly decreases galvanotaxis. Knockdown or inhibition of KCNJ15 prevents PIP3 from distributing to the leading edge. Taken together these data suggest a previously unknown two-molecule sensing mechanism in which KCNJ15/Kir4.2 couples with polyamines in sensing weak electric fields.

Abstract-In an optical WDM mesh network, different protection schemes (such as dedicated or shared protection) can be used to improve the service availability against network failures. However, in order to satisfy a connection's service-availability requirement in a cost-effective and resource-efficient manner, we need a systematic mechanism to select a proper protection scheme for each connection request while provisioning the connection. In this paper, we propose to use connection availability as a metric to provide differentiated protection services in a wavelength-convertible WDM mesh network.We develop a mathematical model to analyze the availabilities of connections with different protection modes (i.e., unprotected, dedicated protected, or shared protected). In the shared-protection case, we investigate how a connection's availability is affected by backup resource sharing. The sharing might cause backup resource contention between several connections when multiple simultaneous (or overlapping) failures occur in the network. Using a continuous-time Markov model, we derive the conditional probability for a connection to acquire backup resources in the presence of backup resource contention. Through this model, we show how the availability of a shared-protected connection can be quantitatively computed.Based on the analytical model, we develop provisioning strategies for a given set of connection demands in which an appropriate, possibly different, level of protection is provided to each connection according to its predefined availability requirement, e.g., 0.999, 0.997. We propose integer linear programming (ILP) and heuristic approaches to provision the connections cost effectively while satisfying the connections' availability requirements. The effectiveness of our provisioning approaches is demonstrated through numerical examples. The proposed provisioning strategies inherently facilitate the service differentiation in optical WDM mesh networks.

Highly random copolymers of ϵ‐caprolactone (CL) and D,L‐lactide (LA) were synthesized by a new catalyst system, rare earth chloride–propylene oxide (PO) system. In the presence of propylene oxide, all rare earth chlorides tested are highly effective for the copolymerization. The influences of reaction conditions on the copolymerization catalyzed by the NdCl3‐5PO system have been investigated in detail. The reactivity ratios of ϵ‐caprolactone and D,L‐lactide were determined and show that the copolymerization with this new rare earth catalyst is closer to ideal copolymerization than reported for other catalysts. The microstructure of copolymer analyzed by 13C‐NMR shows that the monomer units in the copolymer is near to completely random distribution with a short average monomer sequence length. The DSC measurement confirms the high randomness of the chain structure. The mechanism studied by NMR indicates that the rare earth alkoxide generated by the reaction of rare earth chloride with propylene oxide initiates the copolymerization, and then proceeds via a “coordination‐insertion” mechanism with acyl‐oxygen bond cleavage of CL and LA. © 1996 John Wiley & Sons, Inc.

Summary: A novel thermosensitive amphiphilic copolymer of PNIPAm grafted polyphosphazene (PNIPAm‐g‐PPP) has been synthesized through a co‐substitution reaction of poly(dichlorophosphazene) with amino terminated NIPAm oligomer and glycine ethyl ester (GlyEt). The polymer obtained had a molar ratio of 1:5.25 PNIPAm to GlyEt and had a lower critical solution temperature (LCST) near 30 °C. The formation of polymeric micelles was confirmed by fluorescence, dynamic light scattering and transmission electron microscopy measurements.The structure and formation of thermosensitive micelles of poly(N‐isopropylacrylamide) grafted polyphosphazenes synthesized here.imageThe structure and formation of thermosensitive micelles of poly(N‐isopropylacrylamide) grafted polyphosphazenes synthesized here.

Thermally responsive amphiphilic poly(N-isopropylacrylamide) (PNIPAm)-grafted-polyphosphazene (PNIPAm-g-PPP) was synthesized by stepwise cosubstitution of chlorine atoms on polymer backbones with amino-terminated NIPAm oligomers and ethyl glycinate (GlyEt). Polymer structure was confirmed by FT-IR, (1)H NMR, elemental analysis, and GPC. The thermosensitivity of PNIPAm-g-PPP aqueous solution was investigated by turbidity method. The lower critical solution temperature (LCST) of PNIPAm-g-PPP was observed to be approximately 30 degrees C in water, while it was 24 degrees C in 0.1M PBS (pH 7.4). Micellization behavior of PNIPAm-g-PPP in aqueous solution was characterized by fluorescence probe technique, TEM, and DLS. The critical micelle concentration (CMC), thus, determined was 0.0187 g/L. Both TEM and DLS measurement suggested that the diameter of micelles was approximately 190 nm at 20 degrees C. Diflunisal (DIF)-loaded micelles were prepared by dialysis method. In vitro release test at various temperatures was also performed to study the effect of temperature on the drug release profiles. It was demonstrated that DIF release from PNIPAm-g-PPP micelles was slower at the temperature of 37 degrees C than that at 4 degrees C.