Chemotherapeutic effect of a novel temozolomide analog on nasopharyngeal carcinoma in vitro and in vivo.

BackgroundMany patients with nasopharyngeal carcinoma (NPC) face poor prognosis. Due to its hidden anatomical location, the tumor is usually diagnosed quite late, and despite initially successful treatment with radiation and cisplatin, many patients will relapse and succumb to the disease. New treatment options are urgently needed. We have performed preclinical studies to evaluate the potential NPC therapeutic activity of a newly developed analog of temozolomide (TMZ), an alkylating agent that is the current chemotherapeutic standard of care for patients with malignant glioma.ResultsTMZ was covalently conjugated to the natural monoterpene perillyl alcohol (POH), creating the novel fusion compound NEO212. Its impact on two NPC cell lines was studied through colony formation assays, cell death ELISA, immunoblots, and in vivo testing in tumor-bearing mice. In vitro, NEO212 effectively triggered tumor cell death, and its potency was significantly greater than that of its individual components, TMZ or POH alone. Intriguingly, merely mixing TMZ with POH also was unable to achieve the superior potency of the conjugated compound NEO212. Treatment of NPC cells with NEO212 inactivated the chemoprotective DNA repair protein MGMT (O6-methylguanine methyltransferase), resulting in significant chemosensitization of cells to a second round of drug treatment. When tested in vivo, NEO212 reduced tumor growth in treated animals.ConclusionOur results demonstrate anticancer activity of NEO212 in preclinical NPC models, suggesting that this novel compound should be evaluated further for the treatment of patients with NPC

Exact Partition Function Zeros of a Polymer on a Simple-Cubic Lattice

We study conformational transitions of a polymer on a simple-cubic lattice by calculating the zeros of the exact partition function, up to chain length 24. In the complex temperature plane, two loci of the partition function zeros are found for longer chains, suggesting the existence of both the coil-globule collapse transition and the melting-freezing transition. The locus corresponding to coil-globule transition clearly approaches the real axis as the chain length increases, and the transition temperature could be estimated by finite-size scaling. The form of the logarithmic correction to the scaling of the partition function zeros could also be obtained. The other locus does not show clear scaling behavior, but a supplementary analysis of the specific heat reveals a first-order-like pseudo-transition.Comment: 21 pages, 4 figure

Exact quantum states of a general time-dependent quadratic system from classical action

A generalization of driven harmonic oscillator with time-dependent mass and frequency, by adding total time-derivative terms to the Lagrangian, is considered. The generalization which gives a general quadratic Hamiltonian system does not change the classical equation of motion. Based on the observation by Feynman and Hibbs, the propagators (kernels) of the systems are calculated from the classical action, in terms of solutions of the classical equation of motion: two homogeneous and one particular solutions. The kernels are then used to find wave functions which satisfy the Schr\"{o}dinger equation. One of the wave functions is shown to be that of a Gaussian pure state. In every case considered, we prove that the kernel does not depend on the way of choosing the classical solutions, while the wave functions depend on the choice. The generalization which gives a rather complicated quadratic Hamiltonian is simply interpreted as acting an unitary transformation to the driven harmonic oscillator system in the Hamiltonian formulation.Comment: Submitted to Phys. Rev.

Core-Clickable PEG-Branch-Azide Bivalent-Bottle-Brush Polymers by ROMP: Grafting-Through and Clicking-To

The combination of highly efficient polymerizations with modular "click" coupling reactions has enabled the synthesis of a wide variety of novel nanoscopic tructures. Here we demonstrate the facile synthesis of a new class of clickable, branched nanostructures, polyethylene glycol (PEG)-branch-azide bivalent-brush polymers, facilitated by "graft-through" ring-opening metathesis polymerization of a branched norbornene-PEG-chloride macromonomer followed by halide-azide exchange. The resulting bivalent-brush polymers possess azide groups at the core near a polynorbornene backbone with PEG chains extended into solution; the structure resembles a unimolecular micelle. We demonstrate copper-catalyzed azide-alkre cycloaddition (CuAAC) "click-to" coupling of a photocleavable doxorubicin (DOX)-alkyne derivative to the azide core. The CuAAC coupling was quantitative across a wide range of nanoscopic sizes (similar to 6-similar to 50 nrn); UV photolysis of the resulting DOX-loaded materials yielded free DOX that was therapeutically effective against human cancer cells

Super-lattice, rhombus, square, and hexagonal standing waves in magnetically driven ferrofluid surface

Standing wave patterns that arise on the surface of ferrofluids by (single frequency) parametric forcing with an ac magnetic field are investigated experimentally. Depending on the frequency and amplitude of the forcing, the system exhibits various patterns including a superlattice and subharmonic rhombuses as well as conventional harmonic hexagons and subharmonic squares. The superlattice arises in a bicritical situation where harmonic and subharmonic modes collide. The rhombic pattern arises due to the non-monotonic dispersion relation of a ferrofluid

Velocity quantization approach of the one-dimensional dissipative harmonic oscillator

Given a constant of motion for the one-dimensional harmonic oscillator with linear dissipation in the velocity, the problem to get the Hamiltonian for this system is pointed out, and the quantization up to second order in the perturbation approach is used to determine the modification on the eigenvalues when dissipation is taken into consideration. This quantization is realized using the constant of motion instead of the Hamiltonian.Comment: 10 pages, 2 figure

Recent Progress on Nonlinear Ultrasonic Testing for Materials Aging in Nuclear Applications

Materials in nuclear power plants are subjected to a variety of time-dependent aging phenomena, depending on their environmental conditions. In many cases, such phenomena cause microstructural changes in the materials before the development of macro scale damage or, eventually, component failure. Nonlinear ultrasonic testing has the potential to probe microstructural characteristics of materials that have undergone aging related changes and can potentially be used to establish structure-property relationships or predict where macro scale damage (e.g., cracking) is likely to occur. In this talk, recent work relating measured material nonlinearity to microstructural changes encountered in nuclear power applications is presented, specifically radiation damage in ferritic steels and weld sensitization in austenitic stainless steels. In the case of radiation damage, it has been established that the formation of BCC Cu nanoprecipitates and changes in dislocation density affect the material nonlinearity. In nonlinearity measurements in the case of weld sensitization (migration of Cr to grain boundaries in the heat affected zone, affecting the local corrosion resistance), it is thought formation of M23C6 carbides at the grain boundaries affects the measured material nonlinearity. Preliminary results are presented

Accuracy of electrocardiographic criteria for atrial enlargement: validation with cardiovascular magnetic resonance

<p>Abstract</p> <p>Background</p> <p>Anatomic atrial enlargement is associated with significant morbidity and mortality. However, atrial enlargement may not correlate with clinical measures such as electrocardiographic (ECG) criteria. Past studies correlating ECG criteria with anatomic measures mainly used inferior M-mode or two-dimensional echocardiographic data. We sought to determine the accuracy of the ECG to predict anatomic atrial enlargement as determined by volumetric cardiovascular magnetic resonance (CMR).</p> <p>Methods</p> <p>ECG criteria for left (LAE) and right atrial enlargement (RAE) were compared to CMR atrial volume index measurements for 275 consecutive subjects referred for CMR (67% males, 51 ± 14 years). ECG criteria for LAE and RAE were assessed by an expert observer blinded to CMR data. Atrial volume index was computed using the biplane area-length method.</p> <p>Results</p> <p>The prevalence of CMR LAE and RAE was 28% and 11%, respectively, and by any ECG criteria was 82% and 5%, respectively. Though nonspecific, the presence of at least one ECG criteria for LAE was 90% sensitive for CMR LAE. The individual criteria P mitrale, P wave axis < 30°, and negative P terminal force in V1 (NPTF-V1) > 0.04s·mm were 88–99% specific although not sensitive for CMR LAE. ECG was insensitive but 96–100% specific for CMR RAE.</p> <p>Conclusion</p> <p>The presence of at least one ECG criteria for LAE is sensitive but not specific for anatomic LAE. Individual criteria for LAE, including P mitrale, P wave axis < 30°, or NPTF-V1 > 0.04s·mm are highly specific, though not sensitive. ECG is highly specific but insensitive for RAE. Individual ECG P wave changes do not reliably both detect and predict anatomic atrial enlargement.</p