Intracellular delivery and ultrasonic activation of folate receptor-targeted phase-change contrast agents in breast cancer cells in vitro

Breast cancer is a diverse and complex disease that remains one of the leading causes of death among women. Novel, outside-of-the-box imaging and treatment methods are needed to supplement currently available technologies. In this study, we present evidence for the intracellular delivery and ultrasound-stimulated activation of folate receptor (FR)-targeted phase-change contrast agents (PCCAs) in MDA-MB-231 and MCF-7 breast cancer cells in vitro. PCCAs are lipid-coated, perfluorocarbon-filled particles formulated as nanoscale liquid droplets capable of vaporization into gaseous microbubbles for imaging or therapy. Cells were incubated with 1:1 decafluorobutane (DFB) / octafluoropropane (OFP) PCCAs for 1 hour, imaged via confocal microscopy, exposed to ultrasound (9 MHz, MI = 1.0 or 1.5), and imaged again after insonation. FR-targeted PCCAs were observed intracellularly in both cell lines, but uptake was significantly greater (p < 0.001) in MDA-MB-231 cells (93.0% internalization at MI = 1.0, 79.5% at MI = 1.5) than MCF-7 cells (42.4% internalization at MI = 1.0, 35.7% at MI = 1.5). Folate incorporation increased the frequency of intracellular PCCA detection 45-fold for MDA-MB-231 cells and 7-fold for MCF-7 cells, relative to untargeted PCCAs. Intracellularly activated PCCAs ranged from 500 nm to 6 microns (IQR = 800 nm – 1.5 microns) with a mean diameter of 1.15 ± 0.59 (SD) microns. The work presented herein demonstrates the feasibility of PCCA intracellular delivery and activation using breast cancer cells, illuminating a new platform toward intracellular imaging or therapeutic delivery with ultrasound

Flexible provisioning of Web service workflows

Web services promise to revolutionise the way computational resources and business processes are offered and invoked in open, distributed systems, such as the Internet. These services are described using machine-readable meta-data, which enables consumer applications to automatically discover and provision suitable services for their workflows at run-time. However, current approaches have typically assumed service descriptions are accurate and deterministic, and so have neglected to account for the fact that services in these open systems are inherently unreliable and uncertain. Specifically, network failures, software bugs and competition for services may regularly lead to execution delays or even service failures. To address this problem, the process of provisioning services needs to be performed in a more flexible manner than has so far been considered, in order to proactively deal with failures and to recover workflows that have partially failed. To this end, we devise and present a heuristic strategy that varies the provisioning of services according to their predicted performance. Using simulation, we then benchmark our algorithm and show that it leads to a 700% improvement in average utility, while successfully completing up to eight times as many workflows as approaches that do not consider service failures

Operation of Alcator C-Mod with high-Z plasma facing components and implications

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On the experimental verification of quantum complexity in linear optics

The first quantum technologies to solve computational problems that are beyond the capabilities of classical computers are likely to be devices that exploit characteristics inherent to a particular physical system, to tackle a bespoke problem suited to those characteristics. Evidence implies that the detection of ensembles of photons, which have propagated through a linear optical circuit, is equivalent to sampling from a probability distribution that is intractable to classical simulation. However, it is probable that the complexity of this type of sampling problem means that its solution is classically unverifiable within a feasible number of trials, and the task of establishing correct operation becomes one of gathering sufficiently convincing circumstantial evidence. Here, we develop scalable methods to experimentally establish correct operation for this class of sampling algorithm, which we implement with two different types of optical circuits for 3, 4, and 5 photons, on Hilbert spaces of up to 50,000 dimensions. With only a small number of trials, we establish a confidence >99% that we are not sampling from a uniform distribution or a classical distribution, and we demonstrate a unitary specific witness that functions robustly for small amounts of data. Like the algorithmic operations they endorse, our methods exploit the characteristics native to the quantum system in question. Here we observe and make an application of a "bosonic clouding" phenomenon, interesting in its own right, where photons are found in local groups of modes superposed across two locations. Our broad approach is likely to be practical for all architectures for quantum technologies where formal verification methods for quantum algorithms are either intractable or unknown.Comment: Comments welcom

Telemedicine and international disaster response: Medical consultation to Armenia and Russia via a telemedicine spacebridge

The Telemedicine Spacebridge, a satellite mediated audio-video-fax link between four U.S. and two Armenian and Russian medical centers, permitted remote American consultants to assist Armenian and Russian physicians in the management of medical problems following the December 1988 earthquake in Armenia and the June 1989 gas explosion near Ufa. During 12 weeks of operations, 247 Armenian and Russian and 175 American medical professionals participated in 34 half-day clinical conferences. 209 patients were discussed, requiring expertise in 20 specialty areas. Telemedicine consultations resulted in altered diagnoses for 54, new diagnostic studies for 70, altered diagnostic processes for 47, and modified treatment plans for 47 of 185 Armenian patients presented. Simultaneous participation of several U.S. medical centers was judged beneficial; quality of data transmission was judged excellent. These results suggest that interactive consultation by remote specialists can provide valuable assistance to onsite physicians and favorably influence clinical decisions in the aftermath of major disasters

Genetic insights into the introduction history of black rats into the eastern Indian Ocean

Islands can be powerful demonstrations of how destructive invasive species can be on endemic faunas and insular ecologies. Oceanic islands in the eastern Indian Ocean have suffered dramatically from the impact of one of the world’s most destructive invasive species, the black rat, causing the loss of endemic terrestrial mammals and ongoing threats to ground-nesting birds. We use molecular genetic methods on both ancient and modern samples to establish the origins and minimum invasion frequencies of black rats on Christmas Island and the Cocos-Keeling Islands. We find that each island group had multiple incursions of black rats from diverse geographic and phylogenetic sources. Furthermore, contemporary black rat populations on these islands are highly admixed to the point of potentially obscuring their geographic sources. These hybridisation events between black rat taxa also pose potential dangers to human populations on the islands from novel disease risks. Threats of ongoing introductions from yet additional geographic sources is highlighted by genetic identifications of black rats found on ships, which provides insight into how recent ship-borne human smuggling activity to Christmas Island can negatively impact its endemic species