A Simple Mathematical-Model and Alternative Paradigm for Certain Chemotherapeutic Regimens

A simplified two-compartment model for cell-specific chemotherapy is analysed by reformulating the governing system of differential equations as a Schrodinger equation in time. With the choice of an exponentially decaying function representing the effects of chemotherapy on cycling tumor cells, the potential function V(t) is a Morse-type potential, well known in the quantum mechanical literature; and the solutions are obtainable in terms of confluent hypergeometric functions (or the related Whittaker functions). Because the chemotherapy is administered periodically, the potential V(t) is periodic also, and use is made of existing theory (Floquet theory) as applied to scattering by periodic potentials in the quantum theory of solids. Corresponding to the existence \u27\u27forbidden energy bands\u27\u27 in that context, it appears that there are \u27\u27forbidden\u27\u27 or inappropriate chemotherapeutic regimens also, in the sense that for some combinations of period, dosage, and cell parameters, no real solutions exist for the system of equations describing the time evolution of cancer cells in each compartment. A similar, but less complex phenomenon may occur for simpler mathematical representations of the regimen. The purpose of this paper is to identify the existence of this phenomenon, at least insofar as this model is concerned, and to examine the implications for clinical activities. This new paradigm, if structually stable (in the sense of the phenomenon occurring in more realistic models of chemotherapy) may be of considerable significance in identifying those regimens which are appropriate for effective chemotherapy, by providing a rational basis for such decisions, rather than by \u27\u27trial and error\u27\u27 (see the statement by Skipper [1] at the conclusion of this paper)

Long-time Behavior of a Two-layer Model of Baroclinic Quasi-geostrophic Turbulence

We study a viscous two-layer quasi-geostrophic beta-plane model that is forced by imposition of a spatially uniform vertical shear in the eastward (zonal) component of the layer flows, or equivalently a spatially uniform north-south temperature gradient. We prove that the model is linearly unstable, but that non-linear solutions are bounded in time by a bound which is independent of the initial data and is determined only by the physical parameters of the model. We further prove, using arguments first presented in the study of the Kuramoto-Sivashinsky equation, the existence of an absorbing ball in appropriate function spaces, and in fact the existence of a compact finite-dimensional attractor, and provide upper bounds for the fractal and Hausdorff dimensions of the attractor. Finally, we show the existence of an inertial manifold for the dynamical system generated by the model's solution operator. Our results provide rigorous justification for observations made by Panetta based on long-time numerical integrations of the model equations

Measurement of the mass of the τ lepton

The mass of the τ lepton has been measured at the Beijing Electron-Positron Collider using the Beijing Spectrometer. A search near threshold for e^+e^-→τ^+τ^- was performed. Candidate events were identified by requiring that one τ decay via τ→eνν¯, and the other via τ→μνν¯. The mass value, obtained from a fit to the energy dependence of the τ^+τ^- cross section, is m_τ=1776.9_(-0.5)^(+0.4)±0.2 MeV

Apoptosome activation, an important molecular instigator in 6-mercaptopurine induced Leydig cell death.

Leydig cells are crucial to the production of testosterone in males. It is unknown if the cancer chemotherapeutic drug, 6-mercaptopurine (6 MP), produces Leydig cell failure among adult survivors of childhood acute lymphoblastic leukemia. Moreover, it is not known whether Leydig cell failure is due to either a loss of cells or an impairment in their function. Herein, we show, in a subset of childhood cancer survivors, that Leydig cell failure is related to the dose of 6 MP. This was extended, in a murine model, to demonstrate that 6 MP exposure induced caspase 3 activation, and the loss of Leydig cells was independent of Bak and Bax activation. The death of these non-proliferating cells was triggered by 6 MP metabolism, requiring formation of both cytosolic reactive oxygen species and thiopurine nucleotide triphosphates. The thiopurine nucleotide triphosphates (with physiological amounts of dATP) uniquely activated the apoptosome. An ABC transporter (Abcc4/Mrp4) reduced the amount of thiopurines, thereby providing protection for Leydig cells. The studies reported here demonstrate that the apoptosome is uniquely activated by thiopurine nucleotides and suggest that 6 MP induced Leydig cell death is likely a cause of Leydig cell failure in some survivors of childhood cancer

Phenotypic Spectrum of Seizure Disorders in MBD5-Associated Neurodevelopmental Disorder

OBJECTIVE: To describe the phenotypic spectrum in patients with MBD5-associated neurodevelopmental disorder (MAND) and seizures; features of MAND include intellectual disability, epilepsy, psychiatric features of aggression and hyperactivity, and dysmorphic features including short stature and microcephaly, sleep disturbance, and ataxia. METHODS: We performed phenotyping on patients with MBD5 deletions, duplications, or point mutations and a history of seizures. RESULTS: Twenty-three patients with MAND and seizures were included. Median seizure onset age was 2.9 years (range 3 days–13 years). The most common seizure type was generalized tonic-clonic; focal, atypical absence, tonic, drop attacks, and myoclonic seizures occurred frequently. Seven children had convulsive status epilepticus and 3 nonconvulsive status epilepticus. Fever, viral illnesses, and hot weather provoked seizures. EEG studies in 17/21 patients were abnormal, typically showing slow generalized spike-wave and background slowing. Nine had drug-resistant epilepsy, although 3 eventually became seizure-free. All but one had moderate-to-severe developmental impairment. Epilepsy syndromes included Lennox-Gastaut syndrome, myoclonic-atonic epilepsy, and infantile spasms syndrome. Behavioral problems in 20/23 included aggression, self-injurious behavior, and sleep disturbance. CONCLUSION: MBD5 disruption may be associated with severe early childhood-onset developmental and epileptic encephalopathy. Because neuropsychiatric dysfunction is common and severe, it should be an important focus of clinical management

An Online Platform for Underwater Image Quality Evaluation

With the miniaturisation of underwater cameras, the volume of available underwater images has been considerably increasing. However, underwater images are degraded by the absorption and scattering of light in water. Image processing methods exist that aim to compensate for these degradations, but there are no standard quality evaluation measures or testing datasets for a systematic empirical comparison. For this reason, we propose PUIQE, an online platform for underwater image quality evaluation, which is inspired by other computer vision areas whose progress has been accelerated by evaluation platforms. PUIQE supports the comparison of methods through standard datasets and objective evaluation measures: quality scores for images uploaded on the platform are automatically computed and published in a leaderboard, which enables the ranking of methods. We hope that PUIQE will stimulate and facilitate the development of underwater image processing algorithms to improve underwater images

A simulation tool for MRPC telescopes of the EEE project

The Extreme Energy Events (EEE) Project is mainly devoted to the study of the secondary cosmic ray radiation by using muon tracker telescopes made of three Multigap Resistive Plate Chambers (MRPC) each. The experiment consists of a telescope network mainly distributed across Italy, hosted in different building structures pertaining to high schools, universities and research centers. Therefore, the possibility to take into account the effects of these structures on collected data is important for the large physics programme of the project. A simulation tool, based on GEANT4 and using GEMC framework, has been implemented to take into account the muon interaction with EEE telescopes and to estimate the effects on data of the structures surrounding the experimental apparata.A dedicated event generator producing realistic muon distributions, detailed geometry and microscopic behavior of MRPCs have been included to produce experimental-like data. The comparison between simulated and experimental data, and the estimation of detector resolutions is here presented and discussed