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Nanoscale drug delivery vehicles can facilitate multimodal therapies of cancer by promoting tumour-selective drug release. However, few are effective because cancer cells develop ways to resist and evade treatment. Here, we introduce a photoactivable multi-inhibitor nanoliposome (PMIL) that imparts light-induced cytotoxicity in synchrony with a photoinitiated and sustained release of inhibitors that suppress tumour regrowth and treatment escape signalling pathways. The PMIL consists of a nanoliposome doped with a photoactivable chromophore (benzoporphyrin derivative, BPD) in the lipid bilayer, and a nanoparticle containing cabozantinib (XL184)--a multikinase inhibitor--encapsulated inside. Near-infrared tumour irradiation, following intravenous PMIL administration, triggers photodynamic damage of tumour cells and microvessels, and simultaneously initiates release of XL184 inside the tumour. A single PMIL treatment achieves prolonged tumour reduction in two mouse models and suppresses metastatic escape in an orthotopic pancreatic tumour model. The PMIL offers new prospects for cancer therapy by enabling spatiotemporal control of drug release while reducing systemic drug exposure and associated toxicities.

Patients with frontotemporal lobar degeneration (FTLD) can show superimposed amyloid pathology, though the impact of amyloid on the clinical presentation of FTLD is not well characterized. This cross-sectional case–control study compared clinical features, fluorodeoxyglucose-positron emission tomography metabolism and gray matter volume loss in 30 patients with familial FTLD in whom amyloid status was confirmed with autopsy or Pittsburgh compound B-PET. Compared to the amyloid-negative patients, the amyloid-positive patients performed significantly worse on several cognitive tests and showed hypometabolism and volume loss in more temporoparietal regions. Our results suggest that in FTLD amyloid positivity is associated with a more Alzheimer’s disease-like pattern of neurodegeneration.

Using data from Census 2000, this report provides demographic and socio-economic information about Asians and Pacific Islanders in same-sex couples in California. In this report, the category “API couples” means couples where both members are Asian or Pacific Islander; “inter-ethnic couples” means couples where only one member is Asian or Pacific Islander; and “non-API couples” indicates couples where neither member is Asian or Pacific Islander.ASIANS AND PACIFIC ISLANDERS IN SAME-SEX COUPLES IN CALIFORNIAIn California, more than 13,000 Asian/Pacific Islanders identified themselves as living with a same-sex partner in Census 2000. They constitute over one-third of the 38,200 Asian/Pacific Islanders in same-sex couples identified in the U.S., more than in any other state.Over seven percent of the individuals in same-sex couples in California are Asian/Pacific Islander and nearly one out of ten of California's same-sex couples include at least one API individual (due to inter-ethnic couples).San Francisco County has the highest rate of API same-sex couples (API householder) (2.2 per 1,000 households), while Los Angeles County has the largest number of API same-sex couples (1,929).Twenty-eight percent of California API same-sex partners report Filipino heritage. Sizable proportions of API same-sex partners are also of Chinese, Vietnamese, Japanese, Korean, Asian Indian, Cambodian, and Taiwanese origin.In California, API same-sex couples are more likely to live in counties with high percentages of Asian/Pacific Islanders in the population than in counties with high percentages of samesex couples in the population.The demographic and socio-economic profile of Asian/Pacific Islanders in same-sex couples is more similar to Asian/Pacific Islanders in different-sex couples than it is to non-APIs in same-sex couples. They differ little from Asian/Pacific Islanders in different-sex couples in terms of citizenship, military service, income, education, rates of public assistance, and rates of employment.Compared with non-APIs in same-sex couples in California, Asian/Pacific Islanders are less likely to be employed (67% v. 71%) and to be U.S. citizens (73% v. 86%). In addition, they have annual individual incomes that are more than $7,500 less than non-APIs in same-sex couples.

The blue whale Balaenopterus musculus is a wide-ranging cetacean that can be found in all oceans. In the North Atlantic, little is known about blue whale distribution and genetic structure, or about the interconnections between areas of aggregations in Icelandic waters, the Azores, Northwest Africa, and the Northwest Atlantic. Seasonal movements and habitat use of blue whales, including the location of breeding and wintering areas, are also poorly understood. We used satellite telemetry to track movements of 23 blue whales from eastern Canada, providing the first record of the migratory movements and winter destinations of western North Atlantic blue whales. Cabot Strait, the largest outlet connecting the Gulf of St. Lawrence to the Atlantic, was identified as the main corridor for movements in and out of this high-latitude feeding area. The Mid-Atlantic Bight, located off the southeastern USA, was identified as a wintering, and possibly breeding or calving, area. We confirmed the extended use of key summer feeding areas in the St. Lawrence Estuary and northwestern Gulf of St. Lawrence into the fall, and provided evidence for new feeding areas off southern Newfoundland and Nova Scotia. Our results indicate that there is likely a strong connectivity among blue whale areas of concentration at northern latitudes. They also suggest sporadic foraging outside the feeding season, and highlight seamounts and other deep ocean structures as potentially important blue whale habitats. Globally, our study emphasizes the large scale (i.e. many thousands of square kilometers) one needs to consider when addressing the conservation issues faced by blue whale populations.

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A high-pressure oil switch for high-energy systems has been developed and tested to repetition rates up to 100 pps in burst mode and test voltages to -300 kV. The switch utilizes high-pressure flowing synthetic oil and advanced mechanical designs to achieve high-performance operation at pressures to 17.24 MPa (2500 psi). Experimental data is presented for both single-shot performance as well as continuous repetition rate performance to 20 pps. Electrode lifetime is evaluated for stainless steel and Elkonite to demonstrate electrode lifetime. Evidence is presented in support of the dependence of switching performance on the geometry of the switch. Index Terms--High pressure, high-voltage switch, liquid dielectric, oil switch, rep-rate switch.

A study is conducted, based on the US census 2000, to highlight an understudied population of lesbian and gay community in Asian and Pacific islanders (API). The analyses shows high rates of child rearing among same-sex couples of API but the same-sex couples, out of which one is API, face tough economic conditions, therefore it is suggested that legal protection that marriage provides would go long way in helping same-sex API couples.

Nikkei put warrants signal an innovation in security development and are emerging as a highly traded issue in the American stock exchange. Investors can use these privately issued puts to hedge or speculate on fluctuations in the Tokyo Stock Exchange. Potential benefits and costs can be better evaluated with information gained from an understanding of the price behavior of Nikkei put warrants. An analysis of prices of privately issued Nikkei put warrants using two alternative pricing models reveal pricing biases although these were insignificant.

An experimental program was undertaken at Pulse Sciences, Inc. to demonstrate a switch technology capable of generating picosecond-risetime, multimegawatt pulses. Various technologies reviewed included laser-triggered GaAs switches, ferrite sharpening lines. and spark gap technologies [11-[3]. The goal of the program was to both identify and demonstrate a technology which could be scaled to hundreds of kilovolts as well as operate at kilohertz repetition rates. A picosecond-risetime, long-lifetime switch ([is greater than or equal to] [10.sup.6] - [10.sup.7] shots) was also required. Review of three technologies showed one near-term candidate for the research program. GaAs switches were found to be both highly developmental and to have short lifetimes at hundreds of kilovolts [4]. Similarly, ferrite sharpening lines appeared to have a voltage limitation. Thus spark gap technology capable of being scaled to much higher repetition rates and energy switching regimes was explored. One such switch, a flowing oil gap switch, was investigated. These subnanosecond-risetime, kilohertz oil switches have been developed and tested at Pulse Sciences, Inc. The development was divided into two phases. During the first phase, a two to three pulse breakdown test at 130 kV was used to measure the recovery characteristics of a large-area oil switch at up to 200 pps. Different geometries were explored along with oil flow rates required. The oil flow experiments and the effect of electrode/flow geometry are reported. Successful test results in the first phase led to the phase II design of a high-repetition-rate modulator based on flowed oil switches that develop pulses tens of nanoseconds in duration. The modulator incorporates three oil switches: (1) a transfer switch, (2) an output switch, and (3) a sharpening switch. Initial operation and parameterization have shown operation and recovery of the oil switches at up to 290 kV and repetition rates of 200 pps respectively. Lower-voltage tests at 140 kV and 170 kV have shown recovery at up to 1250 and 1000 pps. Peak energies of 50 J per pulse have been transferred into a 97 [Omega] resistive load, with a 280 ps risetime[5]. The modulator design and performance are reported. The influence of electrode/flow geometry upon the recovery of oil switches is described, along with the breakdown and other characteristics the switches.