Melanoma and lymphocyte cell-specific targeting incorporated into a heat shock protein cage architecture

Protein cages, including viral capsids, ferritins, and heat shock proteins (Hsps), can serve as nanocontainers for biomedical applications. They are genetically and chemically malleable platforms, with potential as therapeutic and imaging agent delivery systems. Here, both genetic and chemical strategies were used to impart cell-specific targeting to the Hsp cage from Methanococcus jannaschii. A tumor vasculature targeting peptide was incorporated onto the exterior surface of the Hsp cage. This protein cage bound to alpha(v)beta(3) integrin-expressing cells. Cellular tropism was also imparted by conjugating anti-CD4 antibodies to the exterior of Hsp cages. These Ab-Hsp cage conjugates specifically bound to CD4(+) cells. Protein cages have the potential to simultaneously incorporate multiple functionalities, including cell-specific targeting, imaging, and therapeutic agent delivery. We demonstrate the simultaneous incorporation of two functionalities, imaging and cell-specific targeting, onto the Hsp protein cage.     

Photosensitized Oxidation of Tetrabromobisphenol A by Humic Acid in Aqueous Solution†

The brominated flame retardant 3,3′,5,5′‐tetrabromobisphenol A (TBBPA) may accumulate in the environment, including surface waters, and degrade there to potentially toxic products. We have previously shown that singlet oxygen (¹O₂), produced by irradiation of rose bengal with visible light, oxidizes Triton X‐100‐solubilized TBBPA to yield the 2,6‐dibromo‐p‐benzosemiquinone anion radical while consuming oxygen (Environ. Sci. Technol. 42 , 166, 2008). Here, we report that a similar ¹ O ₂ ‐induced oxidation can be initiated in aqueous solutions by the irradiation of TBBPA dissolved in a humic acid (HA) solution. HA is a known weak ¹ O ₂ photosensitizer and we indeed detected the infrared ¹ O ₂ phosphorescence from HA preparations in D ₂ O. When an aqueous preparation of HA was irradiated (λ > 400 nm) in the presence of TBBPA, oxygen was consumed, and the 2,6‐dibromo‐ p ‐benzosemiquinone anion radical was generated and detected using electron paramagnetic resonance. Radical formation and oxygen consumption were inhibited by sodium azide, a singlet oxygen quencher. Our results suggest that solar radiation, in the presence of HA, may play an important role in the photodegradation of TBBPA in the aquatic environment.     

Co-extrusion of multilayer poly(m-xylylene adipimide) nanocomposite films for high oxygen barrier packaging applications

Multilayer packaging films incorporating a montmorillonite layered silicate (MLS)/poly(m-xylylene adipimide) (MXD6) nanocomposite as the oxygen barrier layer and low-density polyethylene (LDPE) as the moisture resistant layer were produced through the co-extrusion process at the laboratory and pilot scale level. Extrusion screw speeds were varied from 30 to 130 rpm in order to produce samples with varying layer thicknesses. The multilayer film structure was scaled up from the laboratory scale to the pilot-level scale based on oxygen transmission data obtained from the laboratory-scale process parameters. Laboratory-scale film results indicated that the film which demonstrated an optimal oxygen transmission rate (OTR) of 0.3 cm³/(m² day) at 60%RH and water vapor transmission rate (WvTR) of 1.4 g/(m² day) at 90%RH had a structure that contained a core barrier film layer of nanocomposite MXD6 that makes up roughly 34% of the total film thickness, with the remainder of the film material consisting of maleic anhydride grafted polyolefin tie layers and LDPE skin layers. The OTR of the films changed as the relative humidity of the test environment was varied from 0 to 90%. However, for the pilot-scale trial it was necessary to reduce the target thickness of the core nylon barrier layer to 22% due to layer-to-layer melt flow instabilities that occurred during processing. The barrier properties of the multi-layer co-extruded films were highly dependant on overall film thickness. The highest performing oxygen barrier pilot-scale film had an OTR of 0.3 cm³/(m² day) (60%RH) and a WvTR of 2.4 g/(m² day) (90%RH) with a core nylon layer of 1.5 mil and a total thickness of 7.7 mil. Correlation of the layer thicknesses to the barrier and mechanical properties of the pilot-scale multilayer films indicated that an increased nanocomposite core layer thickness improved the oxygen barrier performance and decreased film elongation while improving the tear resistance of the films.     

Low frequency vocalizations attributed to sei whales (Balaenoptera borealis)

Low frequency (<100 Hz) downsweep vocalizations were repeatedly recorded from ocean gliders east of Cape Cod, MA in May 2005. To identify the species responsible for this call, arrays of acoustic recorders were deployed in this same area during 2006 and 2007. 70 h of collocated visual observations at the center of each array were used to compare the localized occurrence of this call to the occurrence of three baleen whale species: right, humpback, and sei whales. The low frequency call was significantly associated only with the occurrence of sei whales. On average, the call swept from 82 to 34 Hz over 1.4 s and was most often produced as a single call, although pairs and (more rarely) triplets were occasionally detected. Individual calls comprising the pairs were localized to within tens of meters of one another and were more similar to one another than to contemporaneous calls by other whales, suggesting that paired calls may be produced by the same animal. A synthetic kernel was developed to facilitate automatic detection of this call using spectrogram-correlation methods. The optimal kernel missed 14% of calls, and of all the calls that were automatically detected, 15% were false positives.     

Vocalizations produced by humpback whale (Megaptera novaeangliae) calves recorded in Hawaii

Although humpback whale (Megaptera novaeangliae) calves are reported to vocalize, this has not been measurably verified. During March 2006, an underwater video camera and two-element hydrophone array were used to record nonsong vocalizations from a mother-calf escort off Hawaii. Acoustic data were analyzed; measured time delays between hydrophones provided bearings to 21 distinct vocalizations produced by the male calf. Signals were pulsed (71%), frequency modulated (19%), or amplitude modulated (10%). They were of simple structure, low frequency (mean=220 Hz), brief duration (mean=170 ms), and relatively narrow bandwidth (mean=2 kHz). The calf produced three series of "grunts" when approaching the diver. During winters of the years 2001-2005 in Hawaii, nonsong vocalizations were recorded in 109 (65%) of 169 groups with a calf using an underwater video and single (omnidirectional) hydrophone. Nonsong vocalizations were most common (34 of 39) in lone mother-calf pairs. A subsample from this dataset of 60 signals assessed to be vocalizations provided strong evidence that 10 male and 18 female calves vocalized based on statistical similarity to the 21 verified calf signals, proximity to an isolated calf (27 of 28 calves), strong signal-to-noise ratio, and/or bubble emissions coincident to sound.     

Generic tripartite Bell nonlocality sudden death under local phase noise

We definitively show, using an explicit and broadly applicable model, that local phase noise that is capable of eliminating state coherence only in the infinite-time limit is capable of eliminating nonlocality in finite time in three two-level systems prepared in the Bell-nonlocal tripartite states of the generic entanglement class.     

SLM device for 193 nm lithographic applications

The imaging capability of a new spatial light modulator, (SLM), a custom MEMS device is presented. Low k₁ factor aerial image measurements show the suitability of the SLM device for a variety of uses including optical maskless lithography (OML) applications.Collaborating with ASML partner companies, a fully programmable 11-million micro-mirror SLM device was designed, fabricated, and tested. Innovative MEMS manufacturing techniques were developed to fabricate the very large number of micro-mirrors on the underlying mixed-signal CMOS control circuitry. The individual eight-micron square mirrors were designed to support conventional, attenuated, and alternating phase-shift lithography.     

How to estimate the Value at Risk under incomplete information

A key problem in financial and actuarial research, and particularly in the field of risk management, is the choice of models so as to avoid systematic biases in the measurement of risk. An alternative consists of relaxing the assumption that the probability distribution is completely known, leading to interval estimates instead of point estimates. In the present contribution, we show how this is possible for the Value at Risk, by fixing only a small number of parameters of the underlying probability distribution. We start by deriving bounds on tail probabilities, and we show how a conversion leads to bounds for the Value at Risk. It will turn out that with a maximum of three given parameters, the best estimates are always realized in the case of a unimodal random variable for which two moments and the mode are given. It will also be shown that a lognormal model results in estimates for the Value at Risk that are much closer to the upper bound than to the lower bound.     

Cationic Pb2 Dumbbells Stabilized in the Highly Covalent Lead Nitridosilicate Pb2Si5N8

Due to the weak oxidative force of N₂, nitrides are only typically formed with the less electronegative metals. Meeting this challenge, we here present Pb₂Si₅N₈, the first nitridosilicate containing highly electron‐affine cations of a metal from the right side of the Zintl border. By using advanced synchrotron X‐ray diffraction, the crystal structure was determined from a tiny single crystal of 1×3×3 μm³ in size, revealing a significantly different bonding situation compared to all other nitridosilicates known so far. Indeed, DFT calculations confirm distinct amounts of covalency not only between Pb and N but also between formal Pb²⁺ cations. Thus, unprecedented cationic Pb₂ dumbbells with a stretching vibration at 117 cm^?1 were found in Pb₂Si₅N₈, the first representative of a crystallographically elucidated lead nitride, stabilized by high amounts of covalency.     

High-efficiency metal-semiconductor-metal photodetectors on heteroepitaxially grown Ge on Si

We demonstrate extremely efficient germanium-on-silicon metal-semiconductor-metal photodetectors with responsivities (R) as high as 0.85 A/W at 1.55 microm and 2V reverse bias. Ge was directly grown on Si by using a novel heteroepitaxial growth technique, which uses multisteps of growth and hydrogen annealing to reduce surface roughness and threading dislocations that form due to the 4.2% lattice mismatch. Photodiodes on such layers exhibit reverse dark currents of 100 mA/cm2 and external quantum efficiency up to 68%. This technology is promising to realize monolithically integrated optoelectronics.