Design Considerations for Tumor-Targeted Nanoparticles

Inorganic/organic hybrid nanoparticles are potentially useful in biomedicine, but to avoid non-specific background fluorescence and long-term toxicity, they need to be cleared from the body within a reasonable timescale1. Previously, we have shown that rigid spherical nanoparticles such as quantum dots can be cleared by the kidneys if they have a hydrodynamic diameter of approximately 5.5 nm and a zwitterionic surface charge2. Here, we show that quantum dots functionalized with high-affinity small-molecule ligands that target tumours can also be cleared by the kidneys if their hydrodynamic diameter is less than this value, which sets an upper limit of 5–10 ligands per quantum dot for renal clearance. Animal models of prostate cancer and melanoma show receptor-specific imaging and renal clearance within 4 h post-injection. This study suggests a set of design rules for the clinical translation of targeted nanoparticles that can be eliminated through the kidneys.National Science Foundation (U.S.) (NSF-0070319)National Institutes of Health (U.S.) (NIH GM68762)National Institutes of Health (U.S.) (NIH grant no. R33-EB-000673)National Institutes of Health (U.S.) ( NIH grant no. R01-CA-115296)National Institutes of Health (U.S.) (MIT-Harvard NanoMedical Consortium (1U54-CA119349, a Center of Cancer Nanotechnology Excellence))Bank of AmericaMedical Foundation, inc. (Charles A. King Trust Postdoctoral Research Fellowship Program)cance

Web-based monitoring tools for Resistive Plate Chambers in the CMS experiment at CERN

The Resistive Plate Chambers (RPC) are used in the CMS experiment at the trigger level and also in the standard offline muon reconstruction. In order to guarantee the quality of the data collected and to monitor online the detector performance, a set of tools has been developed in CMS which is heavily used in the RPC system. The Web-based monitoring (WBM) is a set of java servlets that allows users to check the performance of the hardware during data taking, providing distributions and history plots of all the parameters. The functionalities of the RPC WBM monitoring tools are presented along with studies of the detector performance as a function of growing luminosity and environmental conditions that are tracked over time

Radiation background with the CMS RPCs at the LHC

The Resistive Plate Chambers (RPCs) are employed in the CMS Experiment at the LHC as dedicated trigger system both in the barrel and in the endcap. This article presents results of the radiation background measurements performed with the 2011 and 2012 proton-proton collision data collected by CMS. Emphasis is given to the measurements of the background distribution inside the RPCs. The expected background rates during the future running of the LHC are estimated both from extrapolated measurements and from simulation

A genomic analysis of disease-resistance genes encoding nucleotide binding sites in Sorghum bicolor

A large set of candidate nucleotide-binding site (NBS)-encoding genes related to disease resistance was identified in the sorghum (Sorghum bicolor) genome. These resistance (R) genes were characterized based on their structural diversity, physical chromosomal location and phylogenetic relationships. Based on their N-terminal motifs and leucine-rich repeats (LRR), 50 non-regular NBS genes and 224 regular NBS genes were identified in 274 candidate NBS genes. The regular NBS genes were classified into ten types: CNL, CN, CNLX, CNX, CNXL, CXN, NX, N, NL and NLX. The vast majority (97%) of NBS genes occurred in gene clusters, indicating extensive gene duplication in the evolution of S. bicolor NBS genes. Analysis of the S. bicolor NBS phylogenetic tree revealed two major clades. Most NBS genes were located at the distal tip of the long arms of the ten sorghum chromosomes, a pattern significantly different from rice and Arabidopsis, the NBS genes of which have a random chromosomal distribution

Spatial Stereoresolution for Depth Corrugations May Be Set in Primary Visual Cortex

Stereo “3D” depth perception requires the visual system to extract binocular disparities between the two eyes' images. Several current models of this process, based on the known physiology of primary visual cortex (V1), do this by computing a piecewise-frontoparallel local cross-correlation between the left and right eye's images. The size of the “window” within which detectors examine the local cross-correlation corresponds to the receptive field size of V1 neurons. This basic model has successfully captured many aspects of human depth perception. In particular, it accounts for the low human stereoresolution for sinusoidal depth corrugations, suggesting that the limit on stereoresolution may be set in primary visual cortex. An important feature of the model, reflecting a key property of V1 neurons, is that the initial disparity encoding is performed by detectors tuned to locally uniform patches of disparity. Such detectors respond better to square-wave depth corrugations, since these are locally flat, than to sinusoidal corrugations which are slanted almost everywhere. Consequently, for any given window size, current models predict better performance for square-wave disparity corrugations than for sine-wave corrugations at high amplitudes. We have recently shown that this prediction is not borne out: humans perform no better with square-wave than with sine-wave corrugations, even at high amplitudes. The failure of this prediction raised the question of whether stereoresolution may actually be set at later stages of cortical processing, perhaps involving neurons tuned to disparity slant or curvature. Here we extend the local cross-correlation model to include existing physiological and psychophysical evidence indicating that larger disparities are detected by neurons with larger receptive fields (a size/disparity correlation). We show that this simple modification succeeds in reconciling the model with human results, confirming that stereoresolution for disparity gratings may indeed be limited by the size of receptive fields in primary visual cortex

Observation of a ppb mass threshoud enhancement in \psi^\prime\to\pi^+\pi^-J/\psi(J/\psi\to\gamma p\bar{p}) decay

The decay channel $\psi^\prime\to\pi^+\pi^-J/\psi(J/\psi\to\gamma p\bar{p})$ is studied using a sample of $1.06\times 10^8$ $\psi^\prime$ events collected by the BESIII experiment at BEPCII. A strong enhancement at threshold is observed in the $p\bar{p}$ invariant mass spectrum. The enhancement can be fit with an $S$-wave Breit-Wigner resonance function with a resulting peak mass of $M=1861^{+6}_{-13} {\rm (stat)}^{+7}_{-26} {\rm (syst)} {\rm MeV/}c^2$ and a narrow width that is $\Gamma<38 {\rm MeV/}c^2$ at the 90% confidence level. These results are consistent with published BESII results. These mass and width values do not match with those of any known meson resonance.Comment: 5 pages, 3 figures, submitted to Chinese Physics

An analysis of simple computational strategies to facilitate the design of functional molecular information processors

BACKGROUND: Biological macromolecules (DNA, RNA and proteins) are capable of processing physical or chemical inputs to generate outputs that parallel conventional Boolean logical operators. However, the design of functional modules that will enable these macromolecules to operate as synthetic molecular computing devices is challenging. RESULTS: Using three simple heuristics, we designed RNA sensors that can mimic the function of a seven-segment display (SSD). Ten independent and orthogonal sensors representing the numerals 0 to 9 are designed and constructed. Each sensor has its own unique oligonucleotide binding site region that is activated uniquely by a specific input. Each operator was subjected to a stringent in silico filtering. Random sensors were selected and functionally validated via ribozyme self cleavage assays that were visualized via electrophoresis. CONCLUSIONS: By utilising simple permutation and randomisation in the sequence design phase, we have developed functional RNA sensors thus demonstrating that even the simplest of computational methods can greatly aid the design phase for constructing functional molecular devices. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12859-016-1297-x) contains supplementary material, which is available to authorized users

Neutrophils in cancer: neutral no more

Neutrophils are indispensable antagonists of microbial infection and facilitators of wound healing. In the cancer setting, a newfound appreciation for neutrophils has come into view. The traditionally held belief that neutrophils are inert bystanders is being challenged by the recent literature. Emerging evidence indicates that tumours manipulate neutrophils, sometimes early in their differentiation process, to create diverse phenotypic and functional polarization states able to alter tumour behaviour. In this Review, we discuss the involvement of neutrophils in cancer initiation and progression, and their potential as clinical biomarkers and therapeutic targets

Readmission Rates of Patients Discharged against Medical Advice: A Matched Cohort Study

OBJECTIVE: We compared the readmission rates and the pattern of readmission among patients discharged against medical advice (AMA) to control patients discharged with approval over a one-year follow-up period. METHODS: A retrospective matched-cohort study of 656 patients(328 were discharged AMA) who were followed for one year after their initial hospitalization at an urban university-affiliated teaching hospital in Vancouver, Canada that serves a population with high prevalence of addiction and psychiatric disorders. Multivariate conditional logistic regression was used to examine the independent association of discharge AMA on 14-day related diagnosis hospital readmission. We fit a multivariate conditional negative binomial regression model to examine the readmission frequency ratio between the AMA and non-AMA group. PRINCIPAL FINDINGS: AMA patients were more likely to be homeless (32.3% vs. 11%) and have co-morbid conditions such as psychiatric illnesses, injection drug use, HIV, hepatitis C and previous gastrointestinal bleeding. Patients discharged AMA were more likely to be readmitted: 25.6% vs. 3.4%, p<0.001 by day 14. The AMA group were more likely to be readmitted within 14 days with a related diagnosis than the non-AMA group (Adjusted Odds Ratio 12.0; 95% Confidence Interval [CI]: 3.7-38.9). Patients who left AMA were more likely to be readmitted multiple times at one year compared to the non-AMA group (adjusted frequency ratio 1.6; 95% CI: 1.3-2.0). There was also higher all-cause in-hospital mortality during the 12-month follow-up in the AMA group compared to non-AMA group (6.7% vs. 2.4%, p = 0.01). CONCLUSIONS: Patients discharged AMA were more likely to be homeless and have multiple co-morbid conditions. At one year follow-up, the AMA group had higher readmission rates, were predisposed to multiple readmissions and had a higher in-hospital mortality. Interventions to reduce discharges AMA in high-risk groups need to be developed and tested