Radiosensitization of prostate cancer cells by 2-deoxyglucose

Prostate cancer is the most common malignancy of men. Treatment options include radiotherapy with or without hormonal manipulation and radical prostatectomy. However, there is no effective treatment for disseminated disease. A hallmark of malignancy is abnormal metabolism which also confers survival advantages and contributes to resistance to therapy. In response to exposure to ionizing radiation, metabolic pathways are activated which can protect the cell from irreversible injury. Tumor cell glycolytic activity is elevated and correlates with aggressiveness and radio resistance, indicating that targeting glucose metabolism may sensitize cancer cells to radiation. We have demonstrated that the clonogenic kill of PC3 cells induced by exposure to x-rays was enhanced by the glycolytic inhibitor 2-deoxyglucose (2DG). In contrast, treatment with 2DG failed to inhibit growth of multicellular spheroids derived from LNCaP cells. However, 2DG treatment, in the absence of irradiation, induced similar toxicity to PC3 and LNCaP cells cultured as monolayers. Radiation-induced cell cycle arrest was prevented by the simultaneous administration of 2DG in both cell lines, indicating a possible mechanism underlying sensitization. Therefore, we hypothesise that observed differences in cellular response to incubation with 2DG in the presence or absence of ionizing radiation resulted from variation in metabolic processes between tumor cell types. We conclude that inhibition of glucose metabolism by 2DG is an effective method for sensitizing prostate cancer cells to experimental radiotherapy and that this may occur by preventing DNA repair during radiation-induced cell cycle arrest

All-optical non-demolition measurement of single-hole spin in a quantum-dot molecule

We propose an all-optical scheme to perform a non-demolition measurement of a single hole spin localized in a quantum-dot molecule. The latter is embedded in a microcavity and driven by two lasers. This allows to induce Raman transitions which entangle the spin state with the polarization of the emitted photons. We find that the measurement can be completed with high fidelity on a timescale of 100 ps, shorter than the typical T2. Furthermore, we show that the scheme can be used to induce and observe spin oscillations without the need of time-dependent magnetic fields

Radiosensitization of noradrenaline transporter-expressing tumour cells by proteasome inhibitors and the role of reactive oxygen species

Background The radiopharmaceutical 131I-metaiodobenzylguanidine (131I-MIBG) is used for the targeted radiotherapy of noradrenaline transporter (NAT)-expressing neuroblastoma. Enhancement of 131I-MIBG's efficacy is achieved by combination with the topoisomerase I inhibitor topotecan - currently being evaluated clinically. Proteasome activity affords resistance of tumour cells to radiation and topoisomerase inhibitors. Therefore, the proteasome inhibitor bortezomib was evaluated with respect to its cytotoxic potency as a single agent and in combination with 131I-MIBG and topotecan. Since elevated levels of reactive oxygen species (ROS) are induced by bortezomib, the role of ROS in tumour cell kill was determined following treatment with bortezomib or the alternative proteasome inhibitor, MG132.<p></p> Methods Clonogenic assay and growth of tumour xenografts were used to investigate the effects of proteasome inhibitors alone or in combination with radiation treatment. Synergistic interactions in vitro were evaluated by combination index analysis. The dependency of proteasome inhibitor-induced clonogenic kill on ROS generation was assessed using antioxidants.<p></p> Results Bortezomib, in the dose range 1 to 30 nM, decreased clonogenic survival of both SK-N-BE(2c) and UVW/NAT cells, and this was prevented by antioxidants. It also acted as a sensitizer in vitro when administered with X-radiation, with 131I-MIBG, or with 131I-MIBG and topotecan. Moreover, bortezomib enhanced the delay of the growth of human tumour xenografts in athymic mice when administered in combination with 131I-MIBG and topotecan. MG132 and bortezomib had similar radiosensitizing potency, but only bortezomib-induced cytotoxicity was ROS-dependent.<p></p> Conclusions Proteasome inhibition shows promise for the treatment of neuroblastoma in combination with 131I-MIBG and topotecan. Since the cytotoxicity of MG132, unlike that of bortezomib, was not ROS-dependent, the latter proteasome inhibitor may have a favourable toxicity profile in normal tissues.<p></p&gt

On-Line Learning with Restricted Training Sets: An Exactly Solvable Case

We solve the dynamics of on-line Hebbian learning in large perceptrons exactly, for the regime where the size of the training set scales linearly with the number of inputs. We consider both noiseless and noisy teachers. Our calculation cannot be extended to non-Hebbian rules, but the solution provides a convenient and welcome benchmark with which to test more general and advanced theories for solving the dynamics of learning with restricted training sets.Comment: 19 pages, eps figures included, uses epsfig macr

Ginger Ridge Mutual Housing Association

Mutual Housing Associations offer an alternative model of managing affordable housing projects. This report describes the activities of the Ginger Ridge Mutual Housing Association in Illinois. (Library-derived description)McCray, R. C. (1998). Final report. Retrieved from http://academicarchive.snhu.eduMaster of Science (M.S.)School of Community Economic Developmen

On the magnetospheric ULF wave counterpart of substorm onset

One near‐ubiquitous signature of substorms observed on the ground is the azimuthal structuring of the onset auroral arc in the minutes prior to onset. Termed auroral beads, these optical signatures correspond to concurrent exponential increases in ground ultralow frequency (ULF) wave power and are likely the result of a plasma instability in the magnetosphere. Here, we present a case study showing the development of auroral beads from a Time History of Events and Macroscale Interactions during Substorms (THEMIS) all‐sky camera with near simultaneous exponential increases in auroral brightness, ionospheric and conjugate magnetotail ULF wave power, evidencing their intrinsic link. We further present a survey of magnetic field fluctuations in the magnetotail around substorm onset. We find remarkably similar superposed epoch analyses of ULF power around substorm onset from space and conjugate ionospheric observations. Examining periods of exponential wave growth, we find the ground‐ and space‐based observations to be consistent, with average growth rates of ∼0.01 s−1, lasting for ∼4 min. Cross‐correlation suggests that the space‐based observations lead those on the ground by approximately 1–1.5 min. Meanwhile, spacecraft located premidnight and ∼10 RE downtail are more likely to observe enhanced wave power. These combined observations lead us to conclude that there is a magnetospheric counterpart of auroral beads and exponentially increasing ground ULF wave power. This is likely the result of the linear phase of a magnetospheric instability, active in the magnetotail for several minutes prior to auroral breakup

On the transonic aerodynamics of a compressor blade row

Linearized analyses have been carried out for the induced velocity and pressure fields within a compressor blade row operating in an infinite annulus at transonic Mach numbers of the flow relative to the blades. In addition, the relationship between the induced velocity and the shape of the mean blade surface has been determined. A computational scheme has been developed for evaluating the blade mean surface ordinates and surface pressure distributions. The separation of the effects of a specified blade thickness distribution from the effects of a specified distribution of the blade lift has been established. In this way, blade mean surface shapes that are necessary for the blades to be locally nonlifting have been computed and are presented for two examples of blades with biconvex parabolic arc sections of radially tapering thickness. Blade shapes that are required to achieve a zero thickness, uniform chordwise loading, constant work spanwise loading are also presented for two examples. In addition, corresponding surface pressure distributions are given. The flow relative to the blade tips has a high subsonic Mach number in the examples that have been computed. The results suggest that at near-sonic relative tip speeds the effective blade shape is dominated by the thickness distribution, with the lift distribution playing only a minor role

My Love Am\u27abel: Romance

https://digitalcommons.library.umaine.edu/mmb-vp/4011/thumbnail.jp