Physical principles of local heat therapy for cancer

Local hyperthermia therapy for cancer can produce selective heating of solid tumors on the basis of known physical laws. If energy is deposited in the general region of the tumor, temperature tends to develop in the tumor higher than that in surrounding normal tissues. The goal of therapy is to achieve cytotoxic temperature elevations in the tumor for an adequate period of time, without damaging nearby normal tissues. Several modalities exist for local heat treatment, of which radiofrequency and ultrasound offer the most promise for controlled, localized heating at depth. A paucity of blood flow in the tumor compared to that in adjacent normal tissues can enhance selective tumor heating considerably. The tumor types that have reduced flow in their central regions are especially vulnerable to heat therapy, both because they can be heated more efficiently and because hypoxic and acidotic tumor tissues are more susceptible to damage by heat. This effect is more pronounced in larger tumors, which have smaller surface-to-volume ratios and so lose heat less rapidly by thermal diffusion. Selective heat treatment of larger tumor masses with low blood perfusion, therefore, is physically practical and rational therapy. Vigorous research efforts are now underway at many centers to optimize this approach

Chondroitin Sulfate Proteoglycans Are a Common Component of Neuronal Inclusions and Astrocytic Reaction in Neurodegenerative Diseases

Previously, we showed three differentially sulfated forms of chondroitin sulfate proteoglycans (CSPG) associated with senile plaques, astrocytes and neurofibrillary tangles in Alzheimer\u27s disease. Here, monoclonal antibodies were used to demonstrate CSPGs in other neurodegenerative diseases. CSPGs were found associated with inclusions of Parkinson\u27s, diffuse Lewy body, Pick\u27s diseases, and progressive supranuclear palsy. Reacting astrocytes in each of these neurodegenrative diseases and Huntington\u27s disease showed immunoreactivity for CSPG. CSPG distribution in a variety of neurodegenerative diseases suggests that similar mechanisms may be involved in the accumulation of proteoglycans in a number of filamentous inclusions

Use of Combined Systemic Hypothermia and Local Heat Treatment to Enhance Temperature Differences Between Tumor and Normal Tissues

The feasibility of combining local heat treatment with wholebody hypothermia in an effort to improve therapeutic gain was assessed. Superficial, non perfused phantom tumors were fashioned in eight anesthetized mongrel dogs by transplantation of the spleen from the abdomen to a subcutaneous site on the hind limb. After pretreatment of the animal with the vasodilator hydralazine (0.5 mg/kg, IV) to enhance normal tissue perfusion, the spleen implant was heated with a 2450-MHz microwave diathermy apparatus, first with the animal\u27s core body temperature in the normal range (39°C) and then after the animal had been packed in ice to reduce core temperature to 30°C. Applied power density and temperatures in both the phantom tumor and underlying muscle tissue were recorded during brief interruptions of diathermy until steady-state temperatures had been achieved. Under normothermic conditions with time-averaged applied power of 0.038 W/ml to phantom tumor and 0.014 W/ml to underlying muscle, tumor temperature rose to 45.9 ± l.8°C, while muscle temperature remained at 40.5 ± 0.7°C. During whole-body hypothermia applied power could be increased to 0.114 W/ml in phantom tumor and to 0.025 W/ml in muscle. Muscle temperature rose only to 33.8 ± l.6°C, while that of the nonperfused phantom tumor rose to 53.6 ± 4.3°C with systemic hypothermia. These results are in agreement with predictions based on the bioheat transfer equation, i.e., heat extraction from well-perfused normal tissues is greatly augmented by cooling of the arterial blood, allowing greater power input to the tumor-bearing region, higher tumor temperatures, and enhanced therapeutic gain during local heat treatments of poorly perfused tumor nodules

Theoretical Feasibility of Vasodilator-enhanced Local Tumor Heating

Normal arterioles, in contrast to the abnormal microvasculature of many solid tumors, provide a target for selective drug action that can enhance local heat treatment of the tumors. Measurements of tissue blood flow with radioactive microspheres and estimates of changes in blood flow with thermal clearance methods revealed that vasodilator drugs either decreased or did not alter blood flow in hamster melanoma, rat hepatoma, and canine transmissible venereal tumor, while increasing perfusion in adjacent normal tissues 2 to 4-fold. Solutions of the bio-heat transfer equation, which take into account such selective effects of vasodilators on blood flow in normal tissues, clearly demonstrate improved selective heating for spheroidal tumors over 2 cm in diameter. In the presence of vasodilator drug effect, steady-state center tumor temperatures of 45-50°C can be achieved by increased power input, while surrounding normal tissues remain below 42°C

Midisuperspace-Induced Corrections to the Wheeler De Witt Equation

We consider the midisuperspace of four dimensional spherically symmetric metrics and the Kantowski-Sachs minisuperspace contained in it. We discuss the quantization of the midisuperspace using the fact that the dimensionally reduced Einstein Hilbert action becomes a scalar-tensor theory of gravity in two dimensions. We show that the covariant regularization procedure in the midisuperspace induces modifications into the minisuperspace Wheeler DeWitt equation.Comment: 7 page

Processing quantum information with relativistic motion of atoms

We show that particle detectors, such as two-level atoms, in noninertial motion (or in gravitational fields) could be used to build quantum gates for the processing of quantum information. Concretely, we show that through suitably chosen noninertial trajectories of the detectors the interaction Hamiltonian's time dependence can be modulated to yield arbitrary rotations in the Bloch sphere due to relativistic quantum effects

Vertex Operators in 4D Quantum Gravity Formulated as CFT

We study vertex operators in 4D conformal field theory derived from quantized gravity, whose dynamics is governed by the Wess-Zumino action by Riegert and the Weyl action. Conformal symmetry is equal to diffeomorphism symmetry in the ultraviolet limit, which mixes positive-metric and negative-metric modes of the gravitational field and thus these modes cannot be treated separately in physical operators. In this paper, we construct gravitational vertex operators such as the Ricci scalar, defined as space-time volume integrals of them are invariant under conformal transformations. Short distance singularities of these operator products are computed and it is shown that their coefficients have physically correct sign. Furthermore, we show that conformal algebra holds even in the system perturbed by the cosmological constant vertex operator as in the case of the Liouville theory shown by Curtright and Thorn.Comment: 26 pages, rewrote review part concisely, added explanation

The one-loop elastic coefficients for the Helfrich membrane in higher dimensions

Using a covariant geometric approach we obtain the effective bending couplings for a 2-dimensional rigid membrane embedded into a $(2+D)$-dimensional Euclidean space. The Hamiltonian for the membrane has three terms: The first one is quadratic in its mean extrinsic curvature. The second one is proportional to its Gaussian curvature, and the last one is proportional to its area. The results we obtain are in agreement with those finding that thermal fluctuations soften the 2-dimensional membrane embedded into a 3-dimensional Euclidean space.Comment: 9 page

Estimation of Lower-Body Kinetics from Loading Profile and Kinematics Alone, Without Measured Ground Reaction Forces

Biomechanical models of human motion can estimate kinetic outcomes, such as joint moments, joint forces and muscle forces. Typically, one performs an inverse dynamics (ID) analysis to compute joint moments from joint angles and measured external forces. Sometimes it is impractical to measure ground reaction forces and moments (GRF&M). We devised an empirical method for performing ID analysis of resistance exercises without measured GRF&M. The method solves the multibody dynamics equations of motion with four key assumptions about the GRF&M that reduce the number of unknowns. The assumptions are 1) negligible ground reaction moments, 2) fixed lateral/medial location of the center of pressure (COP), 3) equal fore/aft location of the COP between the feet, and 4) constant angle of the GRF vector relative to the vertical axis in the frontal plane. We used evaluation trials from a spaceflight countermeasure resistance training device to test this approach. Four participants performed squat and deadlift exercises at various loads. We compared results from traditional ID analysis to results without measured GRF&M using our method. We found that joint moment trajectories in the sagittal plane were qualitatively similar in shape between the two methods, and the amount of root mean squared error (RMSE), measured by difference in joint moment impulse, was typically under 10 percent. Non-sagittal joint moment trajectories, which are much lower in overall magnitude, were not qualitatively similar in shape between the two methods. Non-sagittal moments displayed much higher RMSE, with typical values well over 50 percent. These findings were further supported by validation metrics (Sprague and Geers' P and M metrics, Pearson's r correlation coefficient). Based on these findings, we concluded that useful kinetic results are obtained from ID analysis of squat and deadlift exercises, even when GRF&M are not measured, as long as the outcomes of interest lie in the sagittal plane