Ultrasensitive solution-cast quantum dot photodetectors

Solution-processed electronic and optoelectronic devices offer low cost, large device area, physical flexibility and convenient materials integration compared to conventional epitaxially grown, lattice-matched, crystalline semiconductor devices. Although the electronic or optoelectronic performance of these solution-processed devices is typically inferior to that of those fabricated by conventional routes, this can be tolerated for some applications in view of the other benefits. Here we report the fabrication of solution-processed infrared photodetectors that are superior in their normalized detectivity (D*, the figure of merit for detector sensitivity) to the best epitaxially grown devices operating at room temperature. We produced the devices in a single solution-processing step, overcoating a prefabricated planar electrode array with an unpatterned layer of PbS colloidal quantum dot nanocrystals. The devices showed large photoconductive gains with responsivities greater than 10(3) A W(-1). The best devices exhibited a normalized detectivity D* of 1.8 x 10(13) jones (1 jones = 1 cm Hz(1/2) W(-1)) at 1.3 microm at room temperature: today's highest performance infrared photodetectors are photovoltaic devices made from epitaxially grown InGaAs that exhibit peak D* in the 10(12) jones range at room temperature, whereas the previous record for D* from a photoconductive detector lies at 10(11) jones. The tailored selection of absorption onset energy through the quantum size effect, combined with deliberate engineering of the sequence of nanoparticle fusing and surface trap functionalization, underlie the superior performance achieved in this readily fabricated family of devices.     

The inner jet of an active galactic nucleus as revealed by a radio-to-gamma-ray outburst

Blazars are the most extreme active galactic nuclei. They possess oppositely directed plasma jets emanating at near light speeds from accreting supermassive black holes. According to theoretical models, such jets are propelled by magnetic fields twisted by differential rotation of the black hole's accretion disk or inertial-frame-dragging ergosphere. The flow velocity increases outward along the jet in an acceleration and collimation zone containing a coiled magnetic field. Detailed observations of outbursts of electromagnetic radiation, for which blazars are famous, can potentially probe the zone. It has hitherto not been possible to either specify the location of the outbursts or verify the general picture of jet formation. Here we report sequences of high-resolution radio images and optical polarization measurements of the blazar BL Lacertae. The data reveal a bright feature in the jet that causes a double flare of radiation from optical frequencies to TeV gamma-ray energies, as well as a delayed outburst at radio wavelengths. We conclude that the event starts in a region with a helical magnetic field that we identify with the acceleration and collimation zone predicted by the theories. The feature brightens again when it crosses a standing shock wave corresponding to the bright 'core' seen on the images.     

The CRAC channel consists of a tetramer formed by Stim-induced dimerization of Orai dimers

Ca(2+)-release-activated Ca(2+) (CRAC) channels underlie sustained Ca(2+) signalling in lymphocytes and numerous other cells after Ca(2+) liberation from the endoplasmic reticulum (ER). RNA interference screening approaches identified two proteins, Stim and Orai, that together form the molecular basis for CRAC channel activity. Stim senses depletion of the ER Ca(2+) store and physically relays this information by translocating from the ER to junctions adjacent to the plasma membrane, and Orai embodies the pore of the plasma membrane calcium channel. A close interaction between Stim and Orai, identified by co-immunoprecipitation and by F?rster resonance energy transfer, is involved in the opening of the Ca(2+) channel formed by Orai subunits. Most ion channels are multimers of pore-forming subunits surrounding a central channel, which are preassembled in the ER and transported in their final stoichiometry to the plasma membrane. Here we show, by biochemical analysis after cross-linking in cell lysates and intact cells and by using non-denaturing gel electrophoresis without cross-linking, that Orai is predominantly a dimer in the plasma membrane under resting conditions. Moreover, single-molecule imaging of green fluorescent protein (GFP)-tagged Orai expressed in Xenopus oocytes showed predominantly two-step photobleaching, again consistent with a dimeric basal state. In contrast, co-expression of GFP-tagged Orai with the carboxy terminus of Stim as a cytosolic protein to activate the Orai channel without inducing Ca(2+) store depletion or clustering of Orai into punctae yielded mostly four-step photobleaching, consistent with a tetrameric stoichiometry of the active Orai channel. Interaction with the C terminus of Stim thus induces Orai dimers to dimerize, forming tetramers that constitute the Ca(2+)-selective pore. This represents a new mechanism in which assembly and activation of the functional ion channel are mediated by the same triggering molecule.     

Genotype, haplotype and copy-number variation in worldwide human populations

Genome-wide patterns of variation across individuals provide a powerful source of data for uncovering the history of migration, range expansion, and adaptation of the human species. However, high-resolution surveys of variation in genotype, haplotype and copy number have generally focused on a small number of population groups. Here we report the analysis of high-quality genotypes at 525,910 single-nucleotide polymorphisms (SNPs) and 396 copy-number-variable loci in a worldwide sample of 29 populations. Analysis of SNP genotypes yields strongly supported fine-scale inferences about population structure. Increasing linkage disequilibrium is observed with increasing geographic distance from Africa, as expected under a serial founder effect for the out-of-Africa spread of human populations. New approaches for haplotype analysis produce inferences about population structure that complement results based on unphased SNPs. Despite a difference from SNPs in the frequency spectrum of the copy-number variants (CNVs) detected--including a comparatively large number of CNVs in previously unexamined populations from Oceania and the Americas--the global distribution of CNVs largely accords with population structure analyses for SNP data sets of similar size. Our results produce new inferences about inter-population variation, support the utility of CNVs in human population-genetic research, and serve as a genomic resource for human-genetic studies in diverse worldwide populations.     

Complex reorganization and predominant non-homologous repair following chromosomal breakage in karyotypically balanced germline rearrangements and transgenic integration

We defined the genetic landscape of balanced chromosomal rearrangements at nucleotide resolution by sequencing 141 breakpoints from cytogenetically interpreted translocations and inversions. We confirm that the recently described phenomenon of 'chromothripsis' (massive chromosomal shattering and reorganization) is not unique to cancer cells but also occurs in the germline, where it can resolve to a relatively balanced state with frequent inversions. We detected a high incidence of complex rearrangements (19.2%) and substantially less reliance on microhomology (31%) than previously observed in benign copy-number variants (CNVs). We compared these results to experimentally generated DNA breakage-repair by sequencing seven transgenic animals, revealing extensive rearrangement of the transgene and host genome with similar complexity to human germline alterations. Inversion was the most common rearrangement, suggesting that a combined mechanism involving template switching and non-homologous repair mediates the formation of balanced complex rearrangements that are viable, stably replicated and transmitted unaltered to subsequent generations.     

Anthropogenic ocean acidification over the twenty-first century and its impact on calcifying organisms

Today's surface ocean is saturated with respect to calcium carbonate, but increasing atmospheric carbon dioxide concentrations are reducing ocean pH and carbonate ion concentrations, and thus the level of calcium carbonate saturation. Experimental evidence suggests that if these trends continue, key marine organisms--such as corals and some plankton--will have difficulty maintaining their external calcium carbonate skeletons. Here we use 13 models of the ocean-carbon cycle to assess calcium carbonate saturation under the IS92a 'business-as-usual' scenario for future emissions of anthropogenic carbon dioxide. In our projections, Southern Ocean surface waters will begin to become undersaturated with respect to aragonite, a metastable form of calcium carbonate, by the year 2050. By 2100, this undersaturation could extend throughout the entire Southern Ocean and into the subarctic Pacific Ocean. When live pteropods were exposed to our predicted level of undersaturation during a two-day shipboard experiment, their aragonite shells showed notable dissolution. Our findings indicate that conditions detrimental to high-latitude ecosystems could develop within decades, not centuries as suggested previously.     

RNAi-mediated gene silencing in non-human primates

The opportunity to harness the RNA interference (RNAi) pathway to silence disease-causing genes holds great promise for the development of therapeutics directed against targets that are otherwise not addressable with current medicines. Although there are numerous examples of in vivo silencing of target genes after local delivery of small interfering RNAs (siRNAs), there remain only a few reports of RNAi-mediated silencing in response to systemic delivery of siRNA, and there are no reports of systemic efficacy in non-rodent species. Here we show that siRNAs, when delivered systemically in a liposomal formulation, can silence the disease target apolipoprotein B (ApoB) in non-human primates. APOB-specific siRNAs were encapsulated in stable nucleic acid lipid particles (SNALP) and administered by intravenous injection to cynomolgus monkeys at doses of 1 or 2.5 mg kg(-1). A single siRNA injection resulted in dose-dependent silencing of APOB messenger RNA expression in the liver 48 h after administration, with maximal silencing of >90%. This silencing effect occurred as a result of APOB mRNA cleavage at precisely the site predicted for the RNAi mechanism. Significant reductions in ApoB protein, serum cholesterol and low-density lipoprotein levels were observed as early as 24 h after treatment and lasted for 11 days at the highest siRNA dose, thus demonstrating an immediate, potent and lasting biological effect of siRNA treatment. Our findings show clinically relevant RNAi-mediated gene silencing in non-human primates, supporting RNAi therapeutics as a potential new class of drugs.     

"Curing" of Nicotiana attenuata leaves by small mammals does not decrease nicotine contents

Basal leaves of Nicotiana attenuata are frequently found neatly excised at the petiole and piled on rocks or soil in the sun until dry, after which they disappear, sometimes to be found again in the nests of Neotoma lepida . In response to herbivore attack, N. attenuata increases the concentration of nicotine in its leaves, where it functions as an induced defense. Since excision of leaves at the petiole allows for leaf removal without substantially activating this induced defense, and air-drying at high temperatures can volatilize nicotine, we examined the hypothesis that the observed leaf ""curing"" behavior decreased nicotine contents. In a natural population, replicate bundles of excised leaves were allowed to dry in the sun for up to 96 hours and harvested in 10 intervals. Even though surface temperatures reached 63° C during drying, no significant loss of nicotine was observed. In the laboratory, significant losses of nicotine were not observed until leaves were dried at 100° C. Nicotine contents of naturally ""cured"" leaf piles at 4 populations were found to be marginally higher than those of neighboring intact plants from which the leaves were likely harvested. We conclude that mammalian ""curing"" behavior does not reduce nicotine contents and may allow the leaves to be used for insect repellant purposes.     

从克隆羊多利到个性化治疗

 从1865年到世界上首个克隆动物--"克隆羊"诞生的100多年间，人类一直在进行相关研究。有一个问题直到现在仍未得到完全的回答--人类来自于一个单一的细胞，但现在还不完全清楚的是，这样一个单个细胞是如何产生胚胎并形成其他器官的。1865年，著名科学家韦斯曼（Weissmann）认为，细胞的分裂是不平均的，这样导致在细胞分裂之后所获得的结果有各自不同的特点。那么，把细胞分离进行移植到底会产生什么样的结果?正是这样一种对换，导致了克隆技术的研发和发展。