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Small, monodisperse nanogels (∼50-nm radius) were synthesized by free-radical precipitation polymerization and were characterized using a suite of light scattering and chromatography methods. Nanogels were synthesized with either N-isopropylacrylamide or N-isopropylmethacrylamide as the main monomer, with acrylic acid or 4-acrylamidofluorescein as a comonomer and N,N′-methylenebis(acrylamide) as a cross-linker. By varying the surfactant and initiator concentrations, particle size was controlled while maintaining excellent monodispersity. An amine-containing shell was added to these core particles to facilitate subsequent bioconjugation. Successful conjugation of folic acid to the particles was demonstrated as an example of how such materials might be employed in a targeted drug delivery system.

The Middle Jurassic Fourth of July Batholith and cross-cutting mafic dikes have been studied geochronologically, geobarometrically and paleomagnetically to estimate subsequent tectonic motion of the Cache Creek Terrane (CCT) in the northern Canadian Cordillera. 40Ar/39Ar hornblende ages from a granodiorite phase are similar to U–Pb zircon ages and indicate rapid cooling of the batholith upon intrusion, suggesting that the magnetization age is coincident with the 173-Ma crystallization age. Argon ages of biotite from the granodiorite and two mafic dikes have similar ages of ∼165 Ma, which dates cooling through ∼280 °C. Aluminum-in-hornblende geobarometry indicates differential uplift of the batholith across a north–south fault zone along Atlin Lake with >6 km more uplift on its eastern side. Also, the eastern side has been tilted downward to the south–southwest by ∼9°. Combined paleomagnetic data from 20 granitoid and 11 mafic dike sites yield an in situ paleopole at 55°W, 63°N (dp=5°, dm=5°) and a tilt-corrected paleopole at 81°W, 55°N (dp=5°, dm=6°). Compared to the 173-Ma reference pole for the North American craton, the tilt-corrected pole suggests a significant southward translation of 16.1±3.7° and a significant clockwise rotation of 107±7°. The translation estimate is similar to the Jurassic Teslin Crossing pluton in the Stikine Terrane, however, the rotation estimate is very different. This could indicate that the Cache Creek Terrane was at a similar latitude of the Stikine Terrane, but the two were not yet amalgamated.

We are pleased to present the second update to the Encyclopedia of Mineral Names ( The Canadian Mineralogist, Special Publication 1 ). The entries listed below largely describe new species of minerals that have appeared in the literature since mid-1999. A copy of this update will be supplied free of

Quantitative chemical analyses of fluid inclusions in sedimentary and diagenetic minerals can greatly improve our understanding of the chemistry of ancient surface and near surface waters. The environmental scanning electron microscope (ESEM) with an attached X-ray energy dispersive system (EDS) is capable of producing rapid and accurate major element chemical analyses of individual fluid inclusions in crystals of halite greater than about 30 μm in diameter. The ESEM-EDS technique uses the same basic principles as the X-ray microanalysis of frozen fluid inclusions reported by Ayora and Fontarnau [Ayora, C., Fontarnau, R., 1990. X-ray microanalysis of frozen fluid inclusion. Chemical Geology, 89, pp. 135–148.] but operates in a low-vacuum environment, which allows direct observation of the fluid inclusions to be analyzed without the need for a conductive coating. Modifications of the technique of Ayora and Fontarnau [Ayora, C., Fontarnau, R., 1990. X-ray microanalysis of frozen fluid inclusion. Chemical Geology, 89, pp. 135–148.] also include a newly designed sample holder, modified methods for the preparation of standard brine solutions to obtain “glass-like” homogeneous freezing behavior by addition of ethylene glycol, and a technique to obtain flat smooth surfaces on standard brine solutions. The ability to observe samples before analysis led to the discovery of heterogeneous freezing behavior of some standard solutions and fluid inclusions, which adversely influenced measurement reproducibility. The ESEM-EDS technique yielded quantitative results for Ca, Mg, K, SO 4 , and Cl at concentrations above about 0.1 wt.%; for Na, quantitative analyses were achieved at concentrations above 0.5 wt.%. Accuracies for the major elements in aqueous standards were better than 7% and precisions (relative standard deviations) ranged from 2% to 7%. Results on fluid inclusions in laboratory-grown halite gave accuracies of 6% to 10% for Mg, Ca, and K and precisions from 3% to 16%.

The Old Rag Granite is one of several recognized units within the Virginia Blue Ridge Complex generally composed of Grenville-age gneisses and granitoid intrusive rocks. Chemical variation in the Old Rag Granite indicates simple orthomagmatic crystallization from the borders to the core of the pluton. Fractional crystallization of plagioclase, oxides, apatite and zircon accounts for much of the variation. Some trace elements, however, show anomalous behavior in the central part of the pluton. Y and Sr (and possibly Ba and Nb) are enriched whereas Rb and total REE are depleted in the central part of the pluton. Late crystallization of monazite could contribute to the observed REE patterns. It could not, however, account for Rb depletion and Sr enrichment, and no clear relationship between REE data and Th/U ratios are observed. The geochemical patterns indicate overall orthomagmatic crystallization overlain by a late-stage hydrothermal event. An exploration model for uraniferous granites, based upon the uranium deposits at Rossing and Bokan Mountain, included the Precambrian basement of central and northern Virginia in a list of proposed target areas. Geological, mineralogical and whole-rock chemical characteristics show a close association between the Old Rag Granite and the Rossing-type deposits. The uranium (mean 6.9 ppm, range 0.1–19.8 ppm) and thorium (mean 43 ppm, range 3.5–114 ppm) values are anomalous. Th/U ratios average 7.5 and are widely variable, indicating a decoupling of uranium from thorium. Neither U nor Th are lognormally distributed within the Old Rag Granite, requiring an explanation beyond simple removal of U by weathering. Rayleigh fractionation modeling shows that both U and Th, although probably distributed originally by closed-system fractionation, have been subsequently mobilized. Uranium can be lost in an oxidized form by secondary processes such as weathering or hydrothermal alteration. Thorium, however, will be affected only by hydrothermal processes. It is concluded that although primary fractionation was orthomagmatic, the Old Rag Granite was affected by late hydrothermal alteration whereby U was lost from the body and Th was redistributed. Three primary avenues for U migration are possible: (1) the rocks of the Saddleback Mountain Intrusive Suite which may have been contemporaneous with the Old Rag Granite; (2) Paleozoic fault zones that cut the Old Rag pluton; and (3) quartz veins, pegmatites, cupolas and roof pendants of the country-rock Nellysford gneiss that have been lost to erosion. The last option is preferred on geological and geochemical grounds. It is possible that the sedimentary uranium deposits of the adjacent Triassic Culpepper Basin were derived from eroded upper levels of the Old Rag Granite and like intrusives of the Virginia Blue Ridge Complex.

Discrimination criteria are proposed for selecting irregularly shaped and unpolished fine grains for quantitative analyses by energy dipersive X-ray (EDS) spectroscopy. The basic principle is that the energy distribution of the continuum or background radiation is a direct indication of the orientation of the particle surface at the point of analysis. Background spectra were collected from pure elements in various geometric configurations and orientations from which it was observed that the low-energy (

Background Chemoresistance is a major obstacle in cancer treatment. Targeted therapies that enhance cancer cell sensitivity to chemotherapeutic agents have the potential to increase drug efficacy while reducing toxic effects on untargeted cells. Targeted cancer therapy by RNA interference (RNAi) is a relatively new approach that can be used to reversibly silence genes in vivo by selectively targeting genes such as the epidermal growth factor receptor (EGFR), which has been shown to increase the sensitivity of cancer cells to taxane chemotherapy. However, delivery represents the main hurdle for the broad development of RNAi therapeutics. Methods We report here the use of core/shell hydrogel nanoparticles (nanogels) functionalized with peptides that specially target the EphA2 receptor to deliver small interfering RNAs (siRNAs) targeting EGFR. Expression of EGFR was determined by immunoblotting, and the effect of decreased EGFR expression on chemosensitization of ovarian cancer cells after siRNA delivery was investigated. Results Treatment of EphA2 positive Hey cells with siRNA-loaded, peptide-targeted nanogels decreased EGFR expression levels and significantly increased the sensitivity of this cell line to docetaxel (P < 0.05). Nanogel treatment of SK-OV-3 cells, which are negative for EphA2 expression, failed to reduce EGFR levels and did not increase docetaxel sensitivity (P > 0.05). Conclusion This study suggests that targeted delivery of siRNAs by nanogels may be a promising strategy to increase the efficacy of chemotherapy drugs for the treatment of ovarian cancer. In addition, EphA2 is a viable target for therapeutic delivery, and the siRNAs are effectively protected by the nanogel carrier, overcoming the poor stability and uptake that has hindered clinical advancement of therapeutic siRNAs.

A major bottleneck in the development of siRNA therapies is their delivery to the desired cell type or tissue, followed by effective passage across the cell membrane with subsequent silencing of the targeted mRNA. To address this problem, we describe the synthesis of core/shell hydrogel nanoparticles (nanogels) with surface-localized peptides that specifically target ovarian carcinoma cell lines possessing high expression levels of the Eph2A receptor. These nanogels are also demonstrated to be highly effective in the noncovalent encapsulation of siRNA and enable cell-specific delivery of the oligonucleotides in serum-containing medium. Cell toxicity and viability assays reveal that the nanogel construct is nontoxic under the conditions studied, as no toxicity or decrease in cell proliferation is observed following delivery. Importantly, a preliminary investigation of gene silencing illustrates that nanogel-mediated delivery of siRNA targeted to the EGF receptor results in knockdown of that receptor. Excellent protection of siRNA during endosomal uptake and endosomal escape of the nanogels is suggested by these results since siRNA activity in the cytosol is required for gene silencing.

Many of the recent studies of chemical equilibrium in metamorphic rocks may have been hampered by sampling which did not reflect single regions or domains of local equilibration. This paper records results of tests performed to determine the specific volume of rock in chemical equilibrium with respect to a certain phase, under a particular set of conditions. Two samples of high-grade metamorphic gneisses from the Grenville Series of southeastern Ontario were selected for intensive study. The garnets of one specimen, possessing a biotite-garnet-cordierite assemblage, underwent in situ laser microprobe spectrochemical determinations for Fe, Mg, Mn and Ca. Conclusions are thus possible as to the volumes over which free diffusion and chemical equilibrium took place. These volumes were found to be on the order of only a few cubic centimeters and their shapes are strongly controlled by rock structures such as foliation and lineation. A higher-grade pyroxene granulite was also investigated with respect to garnet and biotite equilibrium. Somewhat larger volumes of equilibration were noted in this rock.

Quartz forming in aluminum-saturated environments has a trace aluminum content which varies linearly and directly with its temperature of crystallization. The aluminum content varies at a rate of approximately 1 ppm Al per 3.6° C change in temperature. Use of this geothermometer gives temperatures which are consistent with those expected by geologic reasoning or through the use of other geothermometers.

The proposed geothermometer is very difficult to use mainly for magmatic quartz because they always contain aluminous glassy and crystalline micro-inclusions.

The bulk of this document comprises a thesis by Gerald Markowitz, which is a geochemical study of the Upper Devonian-Lower Mississippian black shales in eastern Kentucky. (DLC)

Mylonites from three widely separated localities along the Fries ductile deformation zone in the Blue Ridge province show substantial enrichments in trace and minor elements (TiO{sub 2}, P{sub 2}O{sub 5}, Zr, Y, and V) and depletions in Rb and Sr relative to the protolith. Two end-member hypotheses can explain the enrichments: one involves partitioning to and from an infiltrating fluid and assumes that all the elements were mobile. The second hypothesis assumes the high-field-strength cations were largely immobile and that their enrichment is due to large volume losses in the mylonites. Modeling indicates that Ti is immobile for fluid/rock ratios as high as 10{sup 4}, and petrographic and modal data support a volume-loss mechanism. Volume loss was accommodated by loss of SiO{sub 2} and alkalies during feldspar dissolution. Calculated fluid/rock volume ratios required to produce the observed SiO{sub 2} losses (assuming Ti mobility) range from 70 to 600. Variable enrichments in P, Zr, Y, and V are attributed to selective mobility of these elements during fluid infiltration.