Two-photon fluorescence materials have attracted much recent attention for their many promising applications, especially in the growing field of biomedical imaging. 1-5 Among the best performing two-photon fluorescence materials are semiconductor quantum dots such as CdSe and related core-shell nanoparticles. 6-8 These quantum dots have been demonstrated in various optical imaging experiments in vitro and in vivo. 6,9,10 At the same time, however, heavy metals as the essential elements in available high-performance semiconductor quantum dots have prompted serious health and environmental concerns in the community and beyond. Therefore, the search for benign alternatives has become increasingly important and urgent. Recently, we found and reported 11 that nanosized pure carbon particles may be surfacepassivated to exhibit bright photoluminescence in the visible. These photoluminescent carbon dots (C-Dots, Figure 1a) are of two distinctive features: one is that the underlying carbon particles are very small (sub-10 nm); and the other is that the particle surface is passivated by organic or other molecules via either covalent linkages or chemical adsorption. 11 Mechanistically, the carbon-based photoluminescence has been attributed to passivated defects on the carbon particle surface acting as excitation energy traps. 11,12 Here we report that the C-Dots also exhibit strong luminescence with two-photon excitation in the near-infrared. The estimated two-photon absorption cross-sections of the C-Dots are comparable to those of available high-performance semiconductor quantum dots. In addition, the two-photon luminescence microscopy imaging of the C-Dots internalized in human cancer cells is demonstrated.

Metastasis is a defining feature of malignant tumors and is the most common cause of cancer-related death, yet the genetics of metastasis are poorly understood. We used massively parallel exome sequencing coupled with Sanger re-sequencing to search for metastasis-related mutations in highly metastatic uveal melanomas of the eye. Inactivating somatic mutations were identified in the gene encoding BRCA1-associated protein 1 (BAP1) on chromosome 3p21.1 in 26 of 31 (84%) metastasizing tumors, including 15 mutations causing premature protein termination, and six affecting its ubiquitin carboxy-terminal hydrolase (UCH) domains. One tumor harbored a frameshift mutation that was germline in origin, thus representing a susceptibility allele. These findings implicate loss of BAP1 in uveal melanoma metastasis and suggest the BAP1 pathway as a therapeutic target.

Many forms of blindness result from the dysfunction or loss of retinal photoreceptors. Induced pluripotent stem cells (iPSC) hold great potential for the modeling of these diseases or as potential therapeutic agents. However, to fulfill this promise, a remaining challenge is to induce human iPSC to recreate in vitro key structural and functional features of the native retina, in particular the presence of photoreceptors with outer-segment discs and light-sensitivity. Here we report that hiPSC can, in a highly autonomous manner, recapitulate spatiotemporally each of the main steps of retinal development observed in vivo and form 3-dimensional retinal cups that contain all major retinal cell types arranged in their proper layers. Moreover, the photoreceptors in our hiPSC-derived retinal tissue achieve advanced maturation, showing the beginning of outer-segment-disc formation and photosensitivity. This success brings us one step closer to the anticipated use of hiPSC for disease modeling and open possibilities for future therapies.

There has been significant recent interest in the development of highly fluorescent nanomaterials as contrast agents for optical imaging in vivo. 1 The imaging agents should ideally be bright, nontoxic, biocompatible, and stable against photobleaching. Among the extensively studied are those based on semiconductor quantum dots (QDs) such as CdSe/ZnS. 2 The rationale for the use of QDs over conventional organic dyes is now generally accepted in the literature. 3 There are already successful in vivo imaging demonstrations of QDs on tumor vasculature, tumor-specific membrane antigens, sentinel lymph nodes, etc. 2,4 The semiconductor QDs containing cadmium or other heavy metals are unfortunately known for their significant toxicity even at relatively low concentrations, 5,6 which may prove prohibitive to any patient studies. Therefore, the search for benign alternatives has continued. Of particular interest and significance was the recent finding that small carbon nanoparticles could be surface-passivated by organic or bio-molecules to become strongly fluorescent. 7 These fluorescent carbon nanoparticles, 7,8 dubbed "carbon dots" (C-Dots, Scheme 1), were found to be physicochemically and photochemically stable and non-blinking. The carbon particle core could also be doped with an inorganic salt such as ZnS before the surface functionalization to significantly enhance the fluorescence brightness (C ZnS -Dots, Scheme 1). 9 These carbon dots have been successfully used for in vitro cell imaging with both one-and two-photon excitations. 7,9,10 Carbon is hardly considered as an intrinsically toxic element. Available results from the ongoing toxicity evaluation of the oligomeric PEG-functionalized C-Dots 7 in mice have suggested no meaningful toxic effects, 11 raising the prospect for in vivo biocompatibility and uses of carbon dots. Here we report the first study of carbon dots for optical imaging in vivo. The results suggest that the carbon dots are not only brightly fluorescent in solution, as reported previously, 7,9 but also well-behaved as contrast agents in live mice.The C-Dots and C ZnS -Dots with the PEG diamine, H 2 NCH 2 (CH 2 CH 2 O) n CH 2 CH 2 CH 2 NH 2 (n ∼ 35, PEG 1500N ), as the surface passivation agent were prepared and characterized as previously reported. 7,9,10 Shown in Figure 1 For subcutaneous injection, female DBA/1 mice (∼25 g) were shaved in the back area surrounding the injection point. Upon the injection of a C-Dots solution (30 µg carbon coreequivalent in 30 µL) or a C ZnS -Dots solution (65 µg in 30 µL), the mice were imagined in a Lumazone FA in vivo Imaging System (MAG Biosystems) with 470 nm (FWHM ∼ 40 nm) excitation and 525 nm (FWHM ∼ 47 nm) emission filters. As shown in Figure 2, the fluorescence images of the subcutaneously injected mice exhibited bright emissions from CDots and C ZnS -Dots. The relatively stronger fluorescence from the latter is consistent with the previously reported solution-phase results. 9 The injected carbon dots in mice diffused relatively slowly, with the ...

Radiocarbon dating is the most widely used dating technique in the world. Recent advances in Accelerator Mass Spectrometry (AMS) and sample preparation techniques have reduced the sample-size requirements by a factor of 1000 and decreased the measurement time from weeks to minutes. Today, it is estimated that more than 90 percent of all measurements made on accelerator mass spectrometers are for radiocarbon age dates. The production of 14 C in the atmosphere varies through time due to changes in the Earth's geomagnetic field intensity and in its concentration, which is regulated by the carbon cycle. As a result of these two variables, a radiocarbon age is not equivalent to a calendar age. Four decades of joint research by the dendrochronology and radiocarbon communities have produced a radiocarbon calibration data set of remarkable precision and accuracy extending from the present to approximately 12,000 calendar years before present. This paper presents high precision paired 230 Th/ 234 U/ 238 U and 14 C age determinations on pristine coral samples that enable us to extend the radiocarbon calibration curve from 12,000 to 50,000 years before present. We developed a statistical model to properly estimate sample age conversion from radiocarbon years to calendar years, taking full account of combined errors in input ages and calibration uncertainties. Our radiocarbon calibration program is publicly accessible at: http://www.radiocarbon.LDEO.columbia.edu/ along with full documentation of the samples, data, and our statistical calibration model. r

Photoluminescent nanomaterials continue to garner research attention because of their many applications. For many years, researchers have focused on quantum dots (QDs) of semiconductor nanocrystals for their excellent performance and predictable fluorescence color variations that depend on the sizes of the nanocrystals. Even with these advantages, QDs can present some major limitations, such as the use of heavy metals in the high-performance semiconductor QDs. Therefore, researchers continue to be interested in developing new QDs or related nanomaterials. Recently, various nanoscale configurations of carbon have emerged as potential new platforms in the development of brightly photoluminescent materials. As a perfect π-conjugated single sheet, graphene lacks electronic bandgaps and is not photoluminescent. Therefore, researchers have created energy bandgaps within graphene as a strategy to impart fluorescence emissions. Researchers have explored many experimental techniques to introduce bandgaps, such as cutting graphene sheets into small pieces or manipulating the π electronic network to form quantum-confined sp(2) "islands" in a graphene sheet, which apparently involve the formation or exploitation of structural defects. In fact, defects in graphene materials not only play a critical role in the creation of bandgaps for emissive electronic transitions, but also contribute directly to the bright photoluminescence emissions observed in these materials. Researchers have found similar defect-derived photoluminescence in carbon nanotubes and small carbon nanoparticles, dubbed carbon "quantum" dots or "carbon dots". However, they have not systematically examined the emissions properties of these different yet related carbon nanomaterials toward understanding their mechanistic origins. In this Account, we examine the spectroscopic features of the observed photoluminescence emissions in graphene materials. We associate the structural characteristics in the underlying graphene materials with those emission properties as a way of classifying them into two primary categories: emissions that originate from created or induced energy bandgaps in a single graphene sheet and emissions that are associated with defects in single- and/or multiple-layer graphene. We highlight the similarities and differences between the observed photoluminescence properties of graphene materials and those found in other carbon nanomaterials including carbon dots and surface defect-passivated carbon nanotubes, and we discuss their mechanistic implications.

Fluorescent carbon dots (small carbon nanoparticles with the surface passivated by oligomeric PEG molecules) were evaluated for their cytotoxicity and in vivo toxicity and also for their optical imaging performance in reference to that of the commercially supplied CdSe/ZnS quantum dots. The results suggested that the carbon dots were biocompatible, and their performance as fluorescence imaging agents was competitive. The implication to the use of carbon dots for in vitro and in vivo applications is discussed.

The photoluminescence in carbon dots (surface-passivated small carbon nanoparticles) could be quenched efficiently by electron acceptor or donor molecules in solution, namely that photo-excited carbon dots are both excellent electron donors and excellent electron acceptors, thus offering new opportunities for their potential uses in light energy conversion and related applications.Quantum-sized semiconductor nanoparticles (quantum dots) have emerged as an important class of photoactive nano-materials for a variety of purposes and applications. [1][2][3][4] For the utilization of semiconductor quantum dots in light energy conversion and related areas, there have been extensive investigations on their photoresponse and photoinduced charge separation and electron transfer processes. [5][6][7][8] Alternative to the traditional semiconductors, other quantum-sized nanoparticles have been explored and developed for similar photophysical and photochemical properties. Of particular interest and significance is the recent finding that small carbon nanoparticles could be surface-passivated by organic molecules or polymers to become highly photoactive, exhibiting strong photoluminescence in the visible and near-infrared spectral regions. 9-15 These photoluminescent carbon nano-particles, dubbed "carbon dots" (Scheme 1), were found to be physico-chemically and photochemically stable and nonblinking in their luminescent emissions. 9 Here we report that the photoluminescence from carbon dots could be quenched highly efficiently by either electron acceptor or electron donor molecules in solution, namely that the photo-excited carbon dots are excellent as both electron donors and electron acceptors. These interesting photoinduced electron transfer properties may offer new opportunities in potentially using carbon dots for light energy conversion and related applications, in addition to their being valuable to the effort on mechanistic elucidation.The carbon dots in this study were prepared by using the same procedures as those reported previously. 9 In the preparation, the small carbon nanoparticles (separated from the laser ablation-produced powdery sample) were refluxed in aqueous nitric acid solution for the purpose of oxidizing surface carbons into carboxylic acids, followed by thionyl chloride treatment and then amidation with the oligomeric ethylene glycol diamine H 2 NCH 2 (C 2 H 4 O) 35 C 2 H 4 CH 2 NH 2 (PEG 1500N ) to form the carbon dots with surface-attached PEGs (Scheme 1). The transmission electron microscopy (TEM) results ( Fig. 1) suggested that these dots were well-dispersed, with sizes averaging about 4.2 nm (based on statistical analyses of more than 300 dots), as also supported by the atomic force microscopy (AFM) results (Fig. 1).Photoluminescence spectra of the carbon dots in aqueous or organic solutions were generally broad ( NIH Public Access Author ManuscriptChem Commun (Camb) 3). Obviously 2,4-dinitrotoluene was a much more effective quencher than 4-nitrotoluene, consistent with its being a s...