Low energy excitations in crystalline perovskite oxides: Evidence from noise experiments

In this paper we report measurements of 1/f noise in a crystalline metallic oxide with perovskite structure down to 4.2K. The results show existence of localized excitations with average activation energy $\approx$ 70-80 meV which produce peak in the noise at T $\approx$ 35-40K. In addition, it shows clear evidence of tunnelling type two-level-systems (as in glasses) which show up in noise measurements below 30K.Comment: 11 pages, 4 figures, to appear in Phys Rev B, vol 58, 1st Dec issu

Low-frequency Current Fluctuations in Individual Semiconducting Single-Wall Carbon Nanotubes

We present a systematic study on low-frequency current fluctuations of nano-devices consisting of one single semiconducting nanotube, which exhibit significant 1/f-type noise. By examining devices with different switching mechanisms, carrier types (electrons vs. holes), and channel lengths, we show that the 1/f fluctuation level in semiconducting nanotubes is correlated to the total number of transport carriers present in the system. However, the 1/f noise level per carrier is not larger than that of most bulk conventional semiconductors, e.g. Si. The pronounced noise level observed in nanotube devices simply reflects on the small number of carriers involved in transport. These results not only provide the basis to quantify the noise behavior in a one-dimensional transport system, but also suggest a valuable way to characterize low-dimensional nanostructures based on the 1/f fluctuation phenomenon

Preclinical PET imaging of bispecific antibody ERY974 targeting CD3 and glypican 3 reveals that tumor uptake correlates to T cell infiltrate

BACKGROUND: Bispecific antibodies redirecting T cells to the tumor obtain increasing interest as potential cancer immunotherapy. ERY974, a full-length bispecific antibody targeting CD3ε on T cells and glypican 3 (GPC3) on tumors, has been in clinical development However, information on the influence of T cells on biodistribution of bispecific antibodies, like ERY974, is scarce. Here, we report the biodistribution and tumor targeting of zirconium-89 (89Zr) labeled ERY974 in mouse models using immuno-positron emission tomography (PET) imaging. METHODS: To study both the role of GPC3 and CD3 on the biodistribution of [89Zr]Zr-N-suc-Df-ERY974, 89Zr-labeled control antibodies targeting CD3 and non-mammalian protein keyhole limpet hemocyanin (KLH) or KLH only were used. GPC3 dependent tumor targeting of [89Zr]Zr-N-suc-Df-ERY974 was tested in xenograft models with different levels of GPC3 expression. In addition, CD3 influence on biodistribution of [89Zr]Zr-N-suc-Df-ERY974 was evaluated by comparing biodistribution between tumor-bearing immunodeficient mice and mice reconstituted with human immune cells using microPET imaging and ex vivo biodistribution. Ex vivo autoradiography was used to study deep tissue distribution. RESULTS: In tumor-bearing immunodeficient mice, [89Zr]Zr-N-suc-Df-ERY974 tumor uptake was GPC3 dependent and specific over [89Zr]Zr-N-suc-Df-KLH/CD3 and [89Zr]Zr-N-suc-Df-KLH/KLH. In mice engrafted with human immune cells, [89Zr]Zr-N-suc-Df-ERY974 specific tumor uptake was higher than in immunodeficient mice. Ex vivo autoradiography demonstrated a preferential distribution of [89Zr]Zr-N-suc-Df-ERY974 to T cell rich tumor tissue. Next to tumor, highest specific [89Zr]Zr-N-suc-Df-ERY974 uptake was observed in spleen and lymph nodes. CONCLUSION: [89Zr]Zr-N-suc-Df-ERY974 can potentially be used to study ERY974 biodistribution in patients to support drug development

Long-range potential fluctuations and 1/f noise in hydrogenated amorphous silicon

We present a microscopic theory of the low-frequency voltage noise (known as "1/f" noise) in micrometer-thick films of hydrogenated amorphous silicon. This theory traces the noise back to the long-range fluctuations of the Coulomb potential produced by deep defects, thereby predicting the absolute noise intensity as a function of the distribution of defect activation energies. The predictions of this theory are in very good agreement with our own experiments in terms of both the absolute intensity and the temperature dependence of the noise spectra.Comment: 8 pages, 3 figures, several new parts and one new figure are added, but no conceptual revision

Molecular Imaging in Cancer Drug Development

Developing new oncology drugs has increased since the improved understanding of cancer's complex biology. The oncology field has become the top therapeutic research area for new drugs. However, only a limited number of drugs entering clinical trials will be approved for use as standard of care for cancer patients. Molecular imaging is increasingly perceived as a tool to support go/no-go decisions early during drug development. It encompasses a wide range of techniques including radiolabeling a compound of interest followed by visualization with single photon emission computed tomography or positron emission tomography. Radiolabeling can be performed using a variety of radionuclides that are preferably matched to the compound based on size and half-life. Imaging can provide information on drug behavior in vivo, whole body drug target visualization, and heterogeneity in drug target expression. This review focuses on current applications of molecular imaging in the development of small molecules, antibodies, and anti-hormonal anticancer drugs

Point process model of 1/f noise versus a sum of Lorentzians

We present a simple point process model of $1/f^{\beta}$ noise, covering different values of the exponent $\beta$. The signal of the model consists of pulses or events. The interpulse, interevent, interarrival, recurrence or waiting times of the signal are described by the general Langevin equation with the multiplicative noise and stochastically diffuse in some interval resulting in the power-law distribution. Our model is free from the requirement of a wide distribution of relaxation times and from the power-law forms of the pulses. It contains only one relaxation rate and yields $1/f^ {\beta}$ spectra in a wide range of frequency. We obtain explicit expressions for the power spectra and present numerical illustrations of the model. Further we analyze the relation of the point process model of $1/f$ noise with the Bernamont-Surdin-McWhorter model, representing the signals as a sum of the uncorrelated components. We show that the point process model is complementary to the model based on the sum of signals with a wide-range distribution of the relaxation times. In contrast to the Gaussian distribution of the signal intensity of the sum of the uncorrelated components, the point process exhibits asymptotically a power-law distribution of the signal intensity. The developed multiplicative point process model of $1/f^{\beta}$ noise may be used for modeling and analysis of stochastic processes in different systems with the power-law distribution of the intensity of pulsing signals.Comment: 23 pages, 10 figures, to be published in Phys. Rev.

Strong Suppression of Electrical Noise in Bilayer Graphene Nano Devices

Low-frequency 1/f noise is ubiquitous, and dominates the signal-to-noise performance in nanodevices. Here we investigate the noise characteristics of single-layer and bilayer graphene nano-devices, and uncover an unexpected 1/f noise behavior for bilayer devices. Graphene is a single layer of graphite, where carbon atoms form a 2D honeycomb lattice. Despite the similar composition, bilayer graphene (two graphene monolayers stacked in the natural graphite order) is a distinct 2D system with a different band structure and electrical properties. In graphene monolayers, the 1/f noise is found to follow Hooge's empirical relation with a noise parameter comparable to that of bulk semiconductors. However, this 1/f noise is strongly suppressed in bilayer graphene devices, and exhibits an unusual dependence on the carrier density, different from most other materials. The unexpected noise behavior in graphene bilayers is associated with its unique band structure that varies with the charge distribution among the two layers, resulting in an effective screening of potential fluctuations due to external impurity charges. The findings here point to exciting opportunities for graphene bilayers in low-noise applications

Seasonal Distribution, Aggregation, and Habitat Selection of Common Carp in Clear Lake, Iowa

The common carp Cyprinus carpio is widely distributed and frequently considered a nuisance species outside its native range. Common carp are abundant in Clear Lake, Iowa, where their presence is both a symptom of degradation and an impediment to improving water quality and the sport fishery. We used radiotelemetry to quantify seasonal distribution, aggregation, and habitat selection of adult and subadult common carp in Clear Lake during 2005–2006 in an effort to guide future control strategies. Over a 22-month period, we recorded 1,951 locations of 54 adults and 60 subadults implanted with radio transmitters. Adults demonstrated a clear tendency to aggregate in an offshore area during the late fall and winter and in shallow, vegetated areas before and during spring spawning. Late-fall and winter aggregations were estimated to include a larger percentage of the tracked adults than spring aggregations. Subadults aggregated in shallow, vegetated areas during the spring and early summer. Our study, when considered in combination with previous research, suggests repeatable patterns of distribution, aggregation, and habitat selection that should facilitate common carp reduction programs in Clear Lake and similar systems

Quantum Size Effect transition in percolating nanocomposite films

We report on unique electronic properties in Fe-SiO2 nanocomposite thin films in the vicinity of the percolation threshold. The electronic transport is dominated by quantum corrections to the metallic conduction of the Infinite Cluster (IC). At low temperature, mesoscopic effects revealed on the conductivity, Hall effect experiments and low frequency electrical noise (random telegraph noise and 1/f noise) strongly support the existence of a temperature-induced Quantum Size Effect (QSE) transition in the metallic conduction path. Below a critical temperature related to the geometrical constriction sizes of the IC, the electronic conductivity is mainly governed by active tunnel conductance across barriers in the metallic network. The high 1/f noise level and the random telegraph noise are consistently explained by random potential modulation of the barriers transmittance due to local Coulomb charges. Our results provide evidence that a lowering of the temperature is somehow equivalent to a decrease of the metal fraction in the vicinity of the percolation limit.Comment: 21 pages, 8 figure

Radiolabeled Monoclonal Antibody Against Colony-Stimulating Factor 1 Receptor Specifically Distributes to the Spleen and Liver in Immunocompetent Mice

Macrophages can promote tumor development. Preclinically, targeting macrophages by colony-stimulating factor 1 (CSF1)/CSF1 receptor (CSF1R) monoclonal antibodies (mAbs) enhances conventional therapeutics in combination treatments. The physiological distribution and tumor uptake of CSF1R mAbs are unknown. Therefore, we radiolabeled a murine CSF1R mAb and preclinically visualized its biodistribution by PET. CSF1R mAb was conjugated to N-succinyl-desferrioxamine (N-suc-DFO) and subsequently radiolabeled with zirconium-89 ((89)Zr). Optimal protein antibody dose was first determined in non-tumor-bearing mice to assess physiological distribution. Next, biodistribution of optimal protein dose and (89)Zr-labeled isotype control was compared with PET and ex vivo biodistribution after 24 and 72 h in mammary tumor-bearing mice. Tissue autoradiography and immunohistochemistry determined radioactivity distribution and tissue macrophage presence, respectively. [(89)Zr]Zr-DFO-N-suc-CSF1R-mAb optimal protein dose was 10 mg/kg, with blood pool levels of 10 ± 2% injected dose per gram tissue (ID/g) and spleen and liver uptake of 17 ± 4 and 11 ± 4%ID/g at 72 h. In contrast, 0.4 mg/kg of [(89)Zr]Zr-DFO-N-suc-CSF1R mAb was eliminated from circulation within 24 h; spleen and liver uptake was 126 ± 44% and 34 ± 7%ID/g, respectively. Tumor-bearing mice showed higher uptake of [(89)Zr]Zr-DFO-N-suc-CSF1R-mAb in the liver, lymphoid tissues, duodenum, and ileum, but not in the tumor than did (89)Zr-labeled control at 72 h. Immunohistochemistry and autoradiography showed that (89)Zr was localized to macrophages within lymphoid tissues. Following [(89)Zr]Zr-DFO-N-suc-CSF1R-mAb administration, tumor macrophages were almost absent, whereas isotype-group tumors contained over 500 cells/mm(2). We hypothesize that intratumoral macrophage depletion by [(89)Zr]Zr-DFO-N-suc-CSF1R-mAb precluded tumor uptake higher than (89)Zr-labeled control. Translation of molecular imaging of macrophage-targeting therapeutics to humans may support macrophage-directed therapeutic development