Are quantum dots ready for in vivo imaging in human subjects?

Nanotechnology has the potential to profoundly transform the nature of cancer diagnosis and cancer patient management in the future. Over the past decade, quantum dots (QDs) have become one of the fastest growing areas of research in nanotechnology. QDs are fluorescent semiconductor nanoparticles suitable for multiplexed in vitro and in vivo imaging. Numerous studies on QDs have resulted in major advancements in QD surface modification, coating, biocompatibility, sensitivity, multiplexing, targeting specificity, as well as important findings regarding toxicity and applicability. For in vitro applications, QDs can be used in place of traditional organic fluorescent dyes in virtually any system, outperforming organic dyes in the majority of cases. In vivo targeted tumor imaging with biocompatible QDs has recently become possible in mouse models. With new advances in QD technology such as bioluminescence resonance energy transfer, synthesis of smaller size non-Cd based QDs, improved surface coating and conjugation, and multifunctional probes for multimodality imaging, it is likely that human applications of QDs will soon be possible in a clinical setting

Band Structure, Phase transitions and Semiconductor Analogs in One-Dimensional Solid Light Systems

The conjunction of atom-cavity physics and photonic structures (``solid light'' systems) offers new opportunities in terms of more device functionality and the probing of designed emulators of condensed matter systems. By analogy to the canonical one-electron approximation of solid state physics, we propose a one-polariton approximation to study these systems. Using this approximation we apply Bloch states to the uniformly tuned Jaynes-Cummings-Hubbard model to analytically determine the energy band structure. By analyzing the response of the band structure to local atom-cavity control we explore its application as a quantum simulator and show phase transition features absent in mean field theory. Using this novel approach for solid light systems we extend the analysis to include detuning impurities to show the solid light analogy of the semiconductor. This investigation also shows new features with no semiconductor analog.Comment: 7 page

Early Gadolinium Enhancement for Area at Risk Determination: A Preclinical Validation Study

Objectives—The aim of this study was to determine if early gadolinium enhancement (EGE) by cardiovascular magnetic resonance (CMR) imaging in a canine model of reperfused myocardial infarction depicts the area at risk (AAR) as determined by microsphere blood flow analysis. Background—It remains controversial whether only the irreversibly injured myocardium enhances when performing CMR imaging in the setting of acute myocardial infarction. Recently, EGE has been proposed as a measure of the AAR in acute myocardial infarction as it correlates well with T2-weighted imaging of the AAR, but still requires pathological validation. Methods—Eleven dogs underwent 2 hours of coronary artery occlusion and 48 hours of reperfusion prior to imaging at 1.5T. EGE imaging was performed 3 minutes after contrast administration with coverage of the entire left ventricle. Late gadolinium enhancement (LGE) imaging was performed between 10 and 15 minutes after contrast injection. AAR was defined as myocardium with blood flow (mL/min/g) \u3c 2SD from remote myocardium determined by microspheres during occlusion. The size of infarction was determined using triphenyltetrazolium chloride (TTC). Results—There was no significant difference in the size of enhancement by EGE compared to the size of AAR by microspheres (44.1± 15.8% vs. 42.7± 9.2%, p=0.61) with good correlation (r=0.88, p \u3c 0.001) and good agreement by Bland-Altman analysis (mean bias 1.4± 17.4%). There was no difference in the size of enhancement by EGE compared to enhancement on native T1 and T2 maps. The size of EGE was significantly greater than the infarct by TTC, (44.1± 15.8% vs. 20.7± 14.4%, p \u3c 0.001) and LGE (44.1± 15.8% vs. 23.5± 12.7%, p \u3c 0.001). Conclusion—At three minutes post-contrast, EGE correlated well with the AAR by microspheres and CMR, and was greater than infarct size. Thus, EGE enhances both reversibly and irreversibly injured myocardium

Analysis of Neptune's 2017 Bright Equatorial Storm

We report the discovery of a large ($\sim$8500 km diameter) infrared-bright storm at Neptune's equator in June 2017. We tracked the storm over a period of 7 months with high-cadence infrared snapshot imaging, carried out on 14 nights at the 10 meter Keck II telescope and 17 nights at the Shane 120 inch reflector at Lick Observatory. The cloud feature was larger and more persistent than any equatorial clouds seen before on Neptune, remaining intermittently active from at least 10 June to 31 December 2017. Our Keck and Lick observations were augmented by very high-cadence images from the amateur community, which permitted the determination of accurate drift rates for the cloud feature. Its zonal drift speed was variable from 10 June to at least 25 July, but remained a constant $237.4 \pm 0.2$ m s$^{-1}$ from 30 September until at least 15 November. The pressure of the cloud top was determined from radiative transfer calculations to be 0.3-0.6 bar; this value remained constant over the course of the observations. Multiple cloud break-up events, in which a bright cloud band wrapped around Neptune's equator, were observed over the course of our observations. No "dark spot" vortices were seen near the equator in HST imaging on 6 and 7 October. The size and pressure of the storm are consistent with moist convection or a planetary-scale wave as the energy source of convective upwelling, but more modeling is required to determine the driver of this equatorial disturbance as well as the triggers for and dynamics of the observed cloud break-up events.Comment: 42 pages, 14 figures, 6 tables; Accepted to Icaru

Adverse prognostic and predictive significance of low DNA-dependent protein kinase catalytic subunit (DNA-PKcs) expression in early-stage breast cancers

Background: DNA-dependent protein kinase catalytic subunit (DNA-PKcs), a serine threonine kinase belonging to the PIKK family (phosphoinositide 3-kinase-like-family of protein kinase), is a critical component of the non-homologous end joining (NHEJ) pathway required for the repair of DNA double strand breaks. DNA-PKcs may be involved in breast cancer pathogenesis. Methods: We evaluated clinicopathological significance of DNA-PKcs protein expression in 1161 tumours and DNA-PKcs mRNA expression in 1950 tumours. We correlated DNA-PKcs to other markers of aggressive phenotypes, DNA repair, apoptosis and cell cycle regulation. Results: Low DNA-PKcs protein expression was associated with higher tumour grade, higher mitotic index, tumour de-differentiation and tumour type (ps<0.05). Absence of BRCA1, low XRCC1/SMUG1/APE1/Polβ were also more likely in low DNA-PKcs expressing tumours (ps<0.05). Low DNA-PKcs protein expression was significantly associated with worse breast cancer specific survival (BCCS) in univariate and multivariate analysis (ps<0.01). At the mRNA level, low DNA-PKcs was associated with PAM50.Her2 and PAM50.LumA molecular phenotypes (ps<0.01) and poor BCSS. In patients with ER positive tumours who received endocrine therapy, low DNA-PKcs (protein and mRNA) was associated with poor survival. In ER negative patients, low DNA-PKcs mRNA remains significantly associated with adverse outcome. Conclusions: Our study suggests that low DNA-PKcs expression may have prognostic and predictive significance in breast cancers

Single Gene Deletions of Orexin, Leptin, Neuropeptide Y, and Ghrelin Do Not Appreciably Alter Food Anticipatory Activity in Mice

Timing activity to match resource availability is a widely conserved ability in nature. Scheduled feeding of a limited amount of food induces increased activity prior to feeding time in animals as diverse as fish and rodents. Typically, food anticipatory activity (FAA) involves temporally restricting unlimited food access (RF) to several hours in the middle of the light cycle, which is a time of day when rodents are not normally active. We compared this model to calorie restriction (CR), giving the mice 60% of their normal daily calorie intake at the same time each day. Measurement of body temperature and home cage behaviors suggests that the RF and CR models are very similar but CR has the advantage of a clearly defined food intake and more stable mean body temperature. Using the CR model, we then attempted to verify the published result that orexin deletion diminishes food anticipatory activity (FAA) but observed little to no diminution in the response to CR and, surprisingly, that orexin KO mice are refractory to body weight loss on a CR diet. Next we tested the orexigenic neuropeptide Y (NPY) and ghrelin and the anorexigenic hormone, leptin, using mouse mutants. NPY deletion did not alter the behavior or physiological response to CR. Leptin deletion impaired FAA in terms of some activity measures, such as walking and rearing, but did not substantially diminish hanging behavior preceding feeding time, suggesting that leptin knockout mice do anticipate daily meal time but do not manifest the full spectrum of activities that typify FAA. Ghrelin knockout mice do not have impaired FAA on a CR diet. Collectively, these results suggest that the individual hormones and neuropepetides tested do not regulate FAA by acting individually but this does not rule out the possibility of their concerted action in mediating FAA

Bacteria in the amniotic fluid without inflammation: Early colonization vs. contamination

Objectives: Intra-amniotic infection, defined by the presence of microorganisms in the amniotic cavity, is often accompanied by intra-amniotic inflammation. Occasionally, laboratories report the growth of bacteria or the presence of microbial nucleic acids in amniotic fluid in the absence of intra-amniotic inflammation. This study was conducted to determine the clinical significance of the presence of bacteria in amniotic fluid samples in the absence of intra-amniotic inflammation. Methods: A retrospective cross-sectional study included 360 patients with preterm labor and intact membranes who underwent transabdominal amniocentesis for evaluation of the microbial state of the amniotic cavity as well as intra-amniotic inflammation. Cultivation techniques were used to isolate microorganisms, and broad-range polymerase chain reaction coupled with electrospray ionization mass spectrometry (PCR/ESI-MS) was utilized to detect the nucleic acids of bacteria, viruses, and fungi. Results: Patients whose amniotic fluid samples evinced microorganisms but did not indicate inflammation had a similar perinatal outcome to those without microorganisms or inflammation [amniocentesis-to-delivery interval (p=0.31), spontaneous preterm birth before 34 weeks (p=0.83), acute placental inflammatory lesions (p=1), and composite neonatal morbidity (p=0.8)]. Conclusions: The isolation of microorganisms from a sample of amniotic fluid in the absence of intra-amniotic inflammation is indicative of a benign condition, which most likely represents contamination of the specimen during the collection procedure or laboratory processing rather than early colonization or infection

Concordance and diagnostic accuracy of vasodilator stress cardiac MRI and 320-detector row coronary CTA

Vasodilator stress cardiac magnetic resonance (CMR) detects ischemia whereas coronary CT angiography (CTA) detects atherosclerosis. The purpose of this study was to determine concordance and accuracy of vasodilator stress CMR and coronary CTA in the same subjects. We studied 151 consecutive subjects referred to detect or exclude suspected obstructive coronary artery disease (CAD) in patients without known disease or recurrent stenosis or ischemia in patients with previously treated CAD. Vasodilator stress CMR was performed on a 1.5 T scanner. CTA was performed on a 320-detector row system. Subjects were followed for cardiovascular events and downstream diagnostic testing. Subjects averaged 56 ± 12 years (60 % male), and 62 % had intermediate pre-test probability for obstructive CAD. Follow-up averaged 450 ± 115 days and was 100 % complete. CMR and CTA agreed in 92 % of cases (κ 0.81, p < 0.001). The event-free survival was 97 % for non-ischemic and 39 % for ischemic CMR (p < 0.0001). The event-free survival was 99 % for non-obstructive and 36 % for obstructive CTA (p < 0.0001). Using a reference standard including quantitative invasive angiography or major cardiovascular events, CMR and CTA had respective sensitivities of 93 and 98 %; specificities of 96 and 96 %; positive predictive values of 91 and 91 %; negative predictive values of 97 and 99 %; and accuracies of 95 and 97 %. Non-ischemic vasodilator stress CMR or non-obstructive coronary CTA were highly concordant and each confer an excellent prognosis. CMR and CTA are both accurate for assessment of obstructive CAD in a predominantly intermediate risk population

Food anticipatory activity on a calorie-restricted diet is independent of Sirt1

A number of studies have demonstrated that the Sirtuin family member, Sirt1, is a key integrator of growth, metabolism, and lifespan. Sirt1 directly interacts with and deacetylates key regulators of the circadian clock, positioning it to be an important link between feeding and circadian rhythms. In fact, one study suggests that Sirt1 is necessary for behavioral anticipation of limited daily food availability, a circadian process termed food anticipatory activity (FAA). In their study, mice overexpressing Sirt1 had enhanced FAA, while mice lacking Sirt1 had little to no FAA. Based on the supposition that Sirt1 was indeed required for FAA, we sought to use Sirt1 deletion to map the neural circuitry responsible for FAA. We began by inactivating Sirt1 using the cell-type specific Cre-driver lines proopiomelanocortin, but after observing no effect on body weight loss or FAA we then moved on to more broadly neuronal Cre drivers Ca2+/calmodulin-dependent protein kinase II and nestin. As neither of these neuronal deletions of Sirt1 had impaired FAA, we then tested 1) a broad postnatal tamoxifen-inducible deletion, 2) a complete, developmental knockout of Sirt1, and 3) a gene replacement, catalytically inactive, form of Sirt1; but all of these mice had FAA similar to controls. Therefore, our findings suggest that FAA is completely independent of Sirt1

Methods for the sampling and analysis of marine aerosols: results from the 2008 GEOTRACES aerosol intercalibration experiment

Atmospheric deposition of trace elements and isotopes (TEI) is an important source of trace metals to the open ocean, impacting TEI budgets and distributions, stimulating oceanic primary productivity, and influencing biological community structure and function. Thus, accurate sampling of aerosol TEIs is a vital component of ongoing GEOTRACES cruises, and standardized aerosol TEI sampling and analysis procedures allow the comparison of data from different sites and investigators. Here, we report the results of an aerosol analysis intercalibration study by seventeen laboratories for select GEOTRACES-relevant aerosol species (Al, Fe, Ti, V, Zn, Pb, Hg, NO3-, and SO42-) for samples collected in September 2008. The collection equipment and filter substrates are appropriate for the GEOTRACES program, as evidenced by low blanks and detection limits relative to analyte concentrations. Analysis of bulk aerosol sample replicates were in better agreement when the processing protocol was constrained (+/- 9% RSD or better on replicate analyses by a single lab, n = 7) than when it was not (generally 20% RSD or worse among laboratories using different methodologies), suggesting that the observed variability was mainly due to methodological differences rather than sample heterogeneity. Much greater variability was observed for fractional solubility of aerosol trace elements and major anions, due to differing extraction methods. Accuracy is difficult to establish without an SRM representative of aerosols, and we are developing an SRM for this purpose. Based on these findings, we provide recommendations for the GEOTRACES program to and macro-nutrients to the open ocean (Okin et al. 2011) and is a key component of the international GEOTRACES program (GEOTRACES Planning Group 2006). A priority of the GEOTRACES program is to quantify both major and trace elements (e. g., Al, Fe, Ti, V, Zn, Pb, and Hg) and species such as nitrate and sulfate in marine aerosols. Therefore, marine aerosol samples collected during GEOTRACES cruises must follow sampling protocols that permit the collection and analysis of as many elements and compounds as possible, while meeting the constraints associated with basin-wide oceanographic cruises (e. g., space limitations, high-frequency sampling, etc.)