Effects of image noise, respiratory motion, and motion compensation on 3D activity quantification in count-limited PET images.

The aims of this study were to evaluate the effects of noise, motion blur, and motion compensation using quiescent-period gating (QPG) on the activity concentration (AC) distribution-quantified using the cumulative AC volume histogram (ACVH)-in count-limited studies such as Y-PET/CT. An International Electrotechnical Commission phantom filled with low F activity was used to simulate clinical Y-PET images. PET data were acquired using a GE-D690 when the phantom was static and subject to 1-4 cm periodic 1D motion.

Evaluation of a deterministic grid-based Boltzmann solver (GBBS) for voxel-level absorbed dose calculations in nuclear medicine.

To evaluate the 3D Grid-based Boltzmann Solver (GBBS) code ATTILA (®) for coupled electron and photon transport in the nuclear medicine energy regime for electron (beta, Auger and internal conversion electrons) and photon (gamma, x-ray) sources. Codes rewritten based on ATTILA are used clinically for both high-energy photon teletherapy and (192)Ir sealed source brachytherapy; little information exists for using the GBBS to calculate voxel-level absorbed doses in nuclear medicine. We compared DOSXYZnrc Monte Carlo (MC) with published voxel-S-values to establish MC as truth.

CFIm25 regulates glutaminase alternative terminal exon definition to modulate miR-23 function.

Alternative polyadenylation (APA) and alternative splicing (AS) provide mRNAs with the means to avoid microRNA repression through selective shortening or differential usage of 3'UTRs. The two glutaminase (GLS) mRNA isoforms, termed KGA and GAC, contain distinct 3'UTRs with the KGA isoform subject to repression by miR-23. We show that depletion of the APA regulator CFIm25 causes a strong shift to the usage of a proximal poly(A) site within the KGA 3'UTR and also alters splicing to favor exclusion of the GAC 3'UTR.

WNT/β-Catenin Signaling Regulates Multiple Steps of Myogenesis by Regulating Step-Specific Targets.

Molecules involved in WNT/β-catenin signaling show specific spatiotemporal expression and play vital roles in myogenesis; however, it is still largely unknown how WNT/β-catenin signaling regulates each step of myogenesis. Here, we show that WNT/β-catenin signaling can control diverse biological processes of myogenesis by regulating step-specific molecules. In order to identify the temporally specific roles of WNT/β-catenin signaling molecules in muscle development and homeostasis, we used in vitro culture systems for both primary mouse myoblasts and C2C12 cells, which can differentiate into myofibers.

Robustness of target dose coverage to motion uncertainties for scanned carbon ion beam tracking therapy of moving tumors.

Beam tracking with scanned carbon ion radiotherapy achieves highly conformal target dose by steering carbon pencil beams to follow moving tumors using real-time magnetic deflection and range modulation. The purpose of this study was to evaluate the robustness of target dose coverage from beam tracking in light of positional uncertainties of moving targets and beams. To accomplish this, we simulated beam tracking for moving targets in both water phantoms and a sample of lung cancer patients using a research treatment planning system.

A revised monitor source method for practical deadtime count loss compensation in clinical planar and SPECT studies.

The aim of the study is to verify the fundamental assumption in the monitor source method, i.e. uniform fractional count loss across the field of view (FOV), and to introduce a revised monitor source method for SPECT deadtime correction that minimally interferes with the clinical protocol.

REV7 is essential for DNA damage tolerance via two REV3L binding sites in mammalian DNA polymerase ζ.

DNA polymerase zeta (pol ζ) is exceptionally important for controlling mutagenesis and genetic instability. REV3L comprises the catalytic subunit, while REV7 (MAD2L2) is considered an accessory subunit. However, it has not been established that the role of REV7 in DNA damage tolerance is necessarily connected with mammalian pol ζ, and there is accumulating evidence that REV7 and REV3L have independent functions.

The nuclear import of ribosomal proteins is regulated by mTOR.

Mechanistic target of rapamycin (mTOR) is a central component of the essential signaling pathway that regulates cell growth and proliferation by controlling anabolic processes in cells. mTOR exists in two distinct mTOR complexes known as mTORC1 and mTORC2 that reside mostly in cytoplasm. In our study, the biochemical characterization of mTOR led to discovery of its novel localization on nuclear envelope where it associates with a critical regulator of nuclear import Ran Binding Protein 2 (RanBP2).

MDM2-mediated degradation of SIRT6 phosphorylated by AKT1 promotes tumorigenesis and trastuzumab resistance in breast cancer.

Sirtuin 6 (SIRT6) is associated with longevity and is also a tumor suppressor. Identification of molecular regulators of SIRT6 might enable its activation therapeutically in cancer patients. In various breast cancer cell lines, we found that SIRT6 was phosphorylated at Ser(338) by the kinase AKT1, which induced the interaction and ubiquitination of SIRT6 by MDM2, targeting SIRT6 for protease-dependent degradation.

4D optimization of scanned ion beam tracking therapy for moving tumors.

Motion mitigation strategies are needed to fully realize the theoretical advantages of scanned ion beam therapy for patients with moving tumors. The purpose of this study was to determine whether a new four-dimensional (4D) optimization approach for scanned-ion-beam tracking could reduce dose to avoidance volumes near a moving target while maintaining target dose coverage, compared to an existing 3D-optimized beam tracking approach. We tested these approaches computationally using a simple 4D geometrical phantom and a complex anatomic phantom, that is, a 4D computed tomogram of the thorax of a lung cancer patient.

Optical artefact characterization and correction in volumetric scintillation dosimetry.

The goals of this study were (1) to characterize the optical artefacts affecting measurement accuracy in a volumetric liquid scintillator detector, and (2) to develop methods to correct for these artefacts. The optical artefacts addressed were photon scattering, refraction, camera perspective, vignetting, lens distortion, the lens point spread function, stray radiation, and noise in the camera. These artefacts were evaluated by theoretical and experimental means, and specific correction strategies were developed for each artefact.