Cancer immunotherapy aims at stimulating the immune system to react against cancer stealth capabilities. It consists of repeatedly injecting small doses of a tumor-associated molecule one wants the immune system to recognize, until a consistent immune response directed against the tumor cells is observed.
We have applied the theory of optimal control to the problem of finding the optimal schedule of injections of an immunotherapeutic agent against cancer. The method employed works for a general ODE system and can be applied to find the optimal protocol in a variety of clinical problems where the kinetics of the drug or treatment and its influence on the normal physiologic functions have been described by a mathematical model.
We show that the choice of the cost function has dramatic effects on the kind of solution the optimization algorithm is able to find. This provides evidence that a careful ODE model and optimization schema must be designed by mathematicians and clinicians using their proper different perspectives. 相似文献
This study describes a rapid method to identify different truffle species by analysis of their volatile compound fraction using static headspace solid-phase microextraction gas chromatography/mass spectrometry. The volatile organic compounds (VOCs) were extracted using a new 2-cm 50/30 microm DVB/CAR/PDMS fiber placed for 10 min in the headspace of the truffle sample with the vial maintained at 20 degrees C (in a thermostatically controlled analysis room). The mass spectra of the VOC chromatograms were represented as 'fingerprints' of the analysed samples. Next, stepwise factorial discriminant analysis afforded a limited number of characteristic fragment ions that allowed a classification of the truffle species studied. This new method provides an effective approach to rapid quality control and identification of truffle species by analysis of their volatile fraction. Moreover, this method offers the advantage of minimizing thermal, mechanical, and chemical modifications of the truffles, thereby reducing the risk of analytical artifacts. 相似文献
Orange crystals of Cs(4)Th(4)P(4)Se(26) were grown from the reaction of (232)Th and P in a Cs(2)Se(3)/Se molten salt flux at 750 degrees C. Cs(4)Th(4)P(4)Se(26) crystallizes in the orthorhombic space group Pbca with the unit cell parameters: a = 12.0130(6), b = 14.5747(7), c = 27.134(1) A; Z = 8. The compound exhibits a three-dimensional structure, consisting of dimeric [Th(2)Se(13)] polyhedral units. The two crystallographically independent, nine-coordinate, bicapped trigonal prismatic thorium atoms share a triangular face to form the dimer, and each dimer edge-shares two selenium atoms with two other dimers to form kinked chains along the [010] direction. While this structure shares features of the previously reported Rb(4)U(4)P(4)Se(26), including phosphorus in the 5+ oxidation state, careful inspection of the structure reveals that the selenophosphate anion that knits the structure together in three directions in both compounds is a unique (P(2)Se(9))(6-) anion. The formula may be described best as [Cs(2)Th(2)(P(2)Se(9))(Se(2))(2)](2). The (P(2)Se(9))(6-) anion features a nearly linear Se-Se-Se backbone with an angle of 171 degrees and Se-Se distances that are approximately 0.2-0.3 A longer than the typical single Se-Se bond. Magnetic studies confirm that this phase contains Th(IV). Raman data for this compound is reported, and structural comparisons will be drawn to its uranium analogue, Rb(4)U(4)P(4)Se(26). 相似文献
Experiments by Gittings, Bandyopadhyay and Durian (Europhys. Lett. 65, 414 (2004)) demonstrate that light possesses a higher probability to propagate in the liquid phase of a foam due to total
reflection. The authors term this observation photon channelling which we investigate in this article theoretically. We first
derive a central relation in the work of Gitting et al. without any free parameters. It links the photon's path-length fraction f in the liquid phase to the liquid fraction ɛ. We then construct two-dimensional Voronoi foams, replace the cell edges by
channels to represent the liquid films and simulate photon paths according to the laws of ray optics using transmission and
reflection coefficients from Fresnel's formulas. In an exact honeycomb foam, the photons show superdiffusive behavior. It
becomes diffusive as soon as disorder is introduced into the foams. The dependence of the diffusion constant on channel width
and refractive index is explained by a one-dimensional random-walk model. It contains a photon channelling state that is crucial
for the understanding of the numerical results. At the end, we shortly comment on the observation that photon channelling
only occurs in a finite range of ɛ. 相似文献
We establish a general existence theory for the Cauchy problem associated with a scalar conservation law in one-space dimension. The flux-function is assumed to be nonconvex and we consider nonclassical entropy solutions selected by a kinetic relation. To solve the Cauchy problem, we construct a sequence of approximate solutions using a wave-front tracking scheme. The main difficulty is deriving a uniform estimate on the total variation of the approximate solutions. This is achieved here by introducing a generalized total variation functional, which is decreasing in time and, additionally, reduces to the standard total variation functional when the solutions contain only classical shocks. This functional seems sufficiently robust to be useful for systems as well.Received: June 3, 2002; revised: November 12, 2002 相似文献
Spinel-structured solids were studied to understand if fast Li+ ion conduction can be achieved with Li occupying multiple crystallographic sites of the structure to form a “Li-stuffed” spinel, and if the concept is applicable to prepare a high mixed electronic-ionic conductive, electrochemically active solid solution of the Li+ stuffed spinel with spinel-structured Li-ion battery electrodes. This could enable a single-phase fully solid electrode eliminating multi-phase interface incompatibility and impedance commonly observed in multi-phase solid electrolyte–cathode composites. Materials of composition Li1.25M(III)0.25TiO4, M(III) = Cr or Al were prepared through solid-state methods. The room-temperature bulk Li+-ion conductivity is 1.63 × 10−4 S cm−1 for the composition Li1.25Cr0.25Ti1.5O4. Addition of Li3BO3 (LBO) increases ionic and electronic conductivity reaching a bulk Li+ ion conductivity averaging 6.8 × 10−4 S cm−1, a total Li-ion conductivity averaging 4.2 × 10−4 S cm−1, and electronic conductivity averaging 3.8 × 10−4 S cm−1 for the composition Li1.25Cr0.25Ti1.5O4 with 1 wt. % LBO. An electrochemically active solid solution of Li1.25Cr0.25Mn1.5O4 and LiNi0.5Mn1.5O4 was prepared. This work proves that Li-stuffed spinels can achieve fast Li-ion conduction and that the concept is potentially useful to enable a single-phase fully solid electrode without interphase impedance. 相似文献
Previous studies demonstrated that reducing the GM3 content in myoblasts increased the cell resistance to hypoxic stress, suggesting that a pharmacological inhibition of the GM3 synthesis could be instrumental for the development of new treatments for ischemic diseases. Herein, the synthesis of several dephosphonated CMP‐Neu5Ac congeners and their anti ‐ GM3‐synthase activity is reported. Biological activity testes revealed that some inhibitors almost completely blocked the GM3‐synthase activity in vitro and reduced the GM3 content in living embryonic kidney 293A cells, eventually activating the epidermal growth factor receptor (EGFR) signaling cascade. 相似文献
This paper introduces a new model of pedestrian flow, formulated within a measure-theoretic framework. It consists of a macroscopic
representation of the system via a family of measures which, pushed forward by some flow maps, provide an estimate of the
space occupancy by pedestrians at successive times. From the modeling point of view, this setting is particularly suitable
for treating nonlocal interactions among pedestrians, obstacles, and wall boundary conditions. In addition, the analysis and
numerical approximation of the resulting mathematical structures, which are the principal objectives of this work, follow
more easily than for models based on standard hyperbolic conservation laws. 相似文献
Single crystal neutron diffraction data have been collected on a sample of enolized 3,4-diacetyl-2,5-hexanedione (tetraacetylethane, TAE) at five temperatures between 20 and 298 K to characterize the temperature-dependent behavior of the short, strong, intramolecular hydrogen bond. Upon decreasing the temperature from 298 K to 20 K, the O2-H1 distance decreases from 1.171(11) to 1.081(2) A and the O1...H1 distance increases from 1.327(10) to 1.416(6) A. The convergence of the C-O bond lengths from inequivalent distances at low temperature to identical values (1.285(4) A) at 298 K is consistent with a resonance-assisted hydrogen bond. However, a rigid bond analysis indicates that the structure at 298 K is disordered. The disorder vanishes at lower temperatures. Short intermolecular C-H...O contacts may be responsible for the ordering at low temperature. The intramolecular O...O distance (2.432 +/- 0.006 A) does not change with temperature. X-ray data at 20 K were measured to analyze the charge density and to gain additional insight into the nature of the strong hydrogen bond. Quantum mechanical calculations demonstrate that periodic boundary conditions provide significant enhancement over gas phase models in that superior agreement with the experimental structure is achieved when applying periodicity. One-dimensional potential energy calculations followed by quantum treatment of the proton reproduce the location of the proton nearer to the O2 site reasonably well, although they overestimate the O-H distance at low temperatures. The choice of the single-point energy calculation strategy for the proton potential is justified by the fact that the proton is preferably located nearer to O2 rather than being equally distant to O1 and O2 or evenly distributed (disordered) between them. 相似文献
Reaction of NaBH4 with (tBuPOCOP)IrHCl affords the previously reported complex (tBuPOCOP)IrH2(BH3) (1) (tBuPOCOP = kappa(3)-C6H3-1,3-[OP(tBu)2]2). The structure of 1 determined from neutron diffraction data contains a B-H sigma-bond to iridium with an elongated B-H bond distance of 1.45(5) A. Compound 1 crystallizes in the space group P1 (Z = 2) with a = 8.262 (5) A, b = 12.264 (5) A, c = 13.394 (4) A, and V = 1256.2 (1) A(3) (30 K). Complex 1 can also be prepared by reaction of BH3 x THF with (tBuPOCOP)IrH2. Reaction of (tBuPOCOP)IrH2 with pinacol borane gave initially complex 2, which is assigned a structure analogous to that of 1 based on spectroscopic measurements. Complex 2 evolves H2 at room temperature leading to the borane complex 3, which is formed cleanly when 2 is subjected to dynamic vacuum. The structure of 3 has been determined by X-ray diffraction and consists of the (tBuPOCOP)Ir core with a sigma-bound pinacol borane ligand in an approximately square planar complex. Compound 3 crystallizes in the space group C2/c (Z = 4) with a = 41.2238 (2) A, b = 11.1233 (2) A, c = 14.6122 (3) A, and V = 6700.21 (19) A(3) (130 K). Reaction of (tBuPOCOP)IrH2 with 9-borobicyclononane (9-BBN) affords complex 4. Complex 4 displays (1)H NMR resonances analogous to 1 and exists in equilibrium with (tBuPOCOP)IrH2 in THF solutions. 相似文献