Overexpression of the nerve growth factor-inducible PC3 immediate early gene is associated with growth inhibition

PC3 (pheochromocytoma cell-3) is an immediate early gene isolated as sequence induced in the rat PC12 cell line during neuronal differentiation by nerve growth factor (NGF). PC3, which is expressed in vivo in the neuroblast when it ceases proliferating and differentiates into a neuron, has partial homology with two antiproliferative genes, BTG1 and Tob. Here we report that overexpression of PC3 in NIH3T3 and PC12 cells leads to marked inhibition of cell proliferation. In stable NIH3T3 clones expressing PC3, the transition from G1 to S phase was impaired, whereas the retinoblastoma (RB) protein was detected as multiple isoforms of M(r) 105,000-115,000 (indicative of a hyperphosphorylated state) only in low-density cultures. Such findings are consistent with a condition of growth inhibition. Thus, PC3 might be a negative regulator of cell proliferation, possibly acting as a transducer of factors influencing cell growth and/or differentiation, such as NGF, by a RB-dependent pathway. This is the first evidence of a NGF-inducible immediate early gene displaying antiproliferative activity

Nontunneling high-order harmonics from ultra-intense laser-driven tightly bound systems

High-order harmonic emission is investigated by numerical solution of the weakly relativistic, two-dimensional Schrödinger equation for the case of ultra-intense laser-driven tightly bound systems (for example, multiply charged ions such as O7+ exposed to laser fields of the order of 1018 W cm-2 at 248 nm). In contrast to their usual substantial decrease, the low-order harmonics having an energy less than the ionization potential exhibit a high efficiency (i.e. intense) plateau with a well defined cutoff. The shape of this plateau is found to depend on the shape of the binding potential. A classical “surfing” mechanism for the generation of these harmonics is proposed that does not involve tunneling and that nevertheless explains the observed cutoff. Thus we call them “nontunneling harmonics.” The significance of relativistic effects for these harmonics is investigated and found to be small, despite the high laser intensity, because of the absence of tunneling

High-order harmonic generation in Xe, Kr, and Ar driven by a 2.1-\mu m source: high-order harmonic spectroscopy under macroscopic effects

We experimentally and numerically study the atomic response and pulse propagation effects of high-order harmonics generated in Xe, Kr, and Ar driven by a 2.1-\mu m infrared femtosecond light source. The light source is an optical parametric chirped-pulse amplifier, and a modified strong-field approximation and 3-dimensional pulse propagation code are used for the numerical simulations. The extended cutoff in the long-wavelength driven high-harmonic generation has revealed the spectral shaping of high-order harmonics due to the atomic structure (or photo-recombination cross-section) and the macroscopic effects, which are the main factors of determining the conversion efficiency besides the driving wavelength. Using precise numerical simulations to determine the macroscopic electron wavepacket, we are able to extract the photo-recombination cross-sections from experimental high-order harmonic spectra in the presence of macroscopic effects. We have experimentally observed that the macroscopic effects shift the observed Cooper minimum of Kr from 80 eV to 60-70 eV and wash out the Cooper minimum of Ar. Measured high-harmonic conversion efficiencies per harmonic near the cutoff are ~10^{-9} for all three gases.Comment: 19 pages, 8 figure

Stem-like and highly invasive prostate cancer cells expressing CD44v8-10 marker originate from CD44-negative cells

In human prostate cancer (PCa), the neuroendocrine cells, expressing the prostate cancer stem cell (CSC) marker CD44, may be resistant to androgen ablation and promote tumor recurrence. During the study of heterogeneity of the highly aggressive neuroendocrine PCa cell lines PC3 and DU-145, we isolated and expanded in vitro a minor subpopulation of very small cells lacking CD44 (CD44neg). Unexpectedly, these sorted CD44neg cells rapidly and spontaneously converted to a stable CD44high phenotype specifically expressing the CD44v8-10 isoform which the sorted CD44high subpopulation failed to express. Surprisingly and potentially interesting, in these cells expression of CD44v8-10 was found to be induced in stem cell medium. CD44 variant isoforms are known to be more expressed in CSC and metastatic cells than CD44 standard isoform. In agreement, functional analysis of the two sorted and cultured subpopulations has shown that the CD44v8-10pos PC3 cells, resulting from the conversion of the CD44neg subpopulation, were more invasive in vitro and had a higher clonogenic potential than the sorted CD44high cells, in that they produced mainly holoclones, known to be enriched in stem-like cells. Of interest, the CD44v8-10 is more expressed in human PCa biopsies than in normal gland. The discovery of CD44v8-10pos cells with stem-like and invasive features, derived from a minoritarian CD44neg cell population in PCa, alerts on the high plasticity of stem-like markers and urges for prudency on the approaches to targeting the putative CSC

An Efficient and Accurate Grid Method for Solving the Time-Dependent Schroedinger Equation: Application of Coulomb Wave Function DVR to Atomic Systems in Strong Laser Fields

We present an efficient and accurate grid method for solving the time-dependent Schr\"{o}dinger equation of atomic systems interacting with intense laser pulses. As usual, the angular part of the wave function is expanded in terms of spherical harmonics. Instead of the usual finite difference (FD) scheme, the radial coordinate is discretized using the discrete variable representation which is constructed from the Coulomb wave function. For an accurate description of the ionization dynamics of atomic systems, the Coulomb wave function discrete variable representation (CWDVR) method needs 3-10 times less grid points than the FD method. The resultant grid points of CWDVR distribute unevenly so that one has finer grid near the origin and coarser one at larger distances. The other important advantage of the CWDVR method is that it treats the Coulomb singularity accurately and gives a good representation of continuum wave functions. The time propagation of the wave function is implemented using the well-known Arnoldi method. As examples, the present method is applied to the multiphoton ionization of both H and H$^-$ in intense laser fields. Short-time excitation and ionization dynamics of H by static electric fields is also investigated. For a wide range of photon energies and laser intensities, ionization rates calculated using this method are in excellent agreement with those from other theoretical calculations.Comment: Submitted to Journal of Chemical Physic

Entanglement Evolution in the Presence of Decoherence

The entanglement of two qubits, each defined as an effective two-level, spin 1/2 system, is investigated for the case that the qubits interact via a Heisenberg XY interaction and are subject to decoherence due to population relaxation and thermal effects. For zero temperature, the time dependent concurrence is studied analytically and numerically for some typical initial states, including a separable (unentangled) initial state. An analytical formula for non-zero steady state concurrence is found for any initial state, and optimal parameter values for maximizing steady state concurrence are given. The steady state concurrence is found analytically to remain non-zero for low, finite temperatures. We also identify the contributions of global and local coherence to the steady state entanglement.Comment: 12 pages, 4 figures. The second version of this paper has been significantly expanded in response to referee comments. The revised manuscript has been accepted for publication in Journal of Physics

Onychomycosis: Recommendations for Diagnosis, Assessment of Treatment Efficacy, and Specialist Referral. The CONSONANCE Consensus Project

Introduction: Onychomycosis is the most common nail disorder in adults, with high recurrence and relapse rates. Its diagnosis may be difficult by non-experts because the clinical signs may overlap with other dermatoses. The treatment may be challenging, as it should be patient-tailored. Methods: An online survey was conducted among European Nail Society (ENS) members to provide recommendations on the diagnosis and assessment of distal lateral subungual onychomycosis (DLSO) in non-specialized clinical environments, as well as recommendations for patient referral. Results: DLSO diagnosis is predominantly based on clinical aspects, and microscopy and fungal culture are commonly employed to establish the diagnosis. Assessment of clinical features is the main method for DLSO follow-up, and the main criterion to define cure is a combination of mycologic cure and clinical cure. The most commonly selected treatments for onychomycosis include oral antifungals, topical antifungals, and nail debridement. According to the nail experts, predisposing factors of DLSO to be evaluated include concurrent tinea pedis diagnosis, immunocompromised status, and diabetes. The minimum clinical aspects to be evaluated for DLSO diagnosis should include subungual hyperkeratosis, white-yellow-orange subungual scales, and absence of salmon-pink coloration. Recommendations for clinical signs that should be evaluated to confirm treatment effectiveness include normal appearance and color of the nail, reduction or absence of scales under the nail, and absence of onycholysis. Recommendations for specialist referral include lack of treatment effectiveness, need of additional therapies, concurrent presence of other diseases or comorbidities, severe DLSO, and presence of a dermatophytoma or involvement of the nail matrix. Conclusions: According to the surveyed nail experts, after evaluating clinical signs and predisposing factors for DLSO, the diagnosis should include subungual hyperkeratosis, nail color (yellow-orange), and onycholysis and thickening. In cases of severe DLSO, when there is treatment failure, concomitant diseases/comorbidities, presence of a dermatophytoma or involvement of the nail matrix, or involvement of several/all nails, referral should be considered

Resonance structures in the multichannel quantum defect theory for the photofragmentation processes involving one closed and many open channels

The transformation introduced by Giusti-Suzor and Fano and extended by Lecomte and Ueda for the study of resonance structures in the multichannel quantum defect theory (MQDT) is used to reformulate MQDT into the forms having one-to-one correspondence with those in Fano's configuration mixing (CM) theory of resonance for the photofragmentation processes involving one closed and many open channels. The reformulation thus allows MQDT to have the full power of the CM theory, still keeping its own strengths such as the fundamental description of resonance phenomena without an assumption of the presence of a discrete state as in CM.Comment: 7 page

Relativistic transition wavelenghts and probabilities for spectral lines of Ne II

Transition wavelengths and probabilities for several 2p4 3p - 2p4 3s and 2p4 3d - 2p4 3p lines in fuorine-like neon ion (NeII) have been calculated within the multiconfiguration Dirac-Fock (MCDF) method with quantum electrodynamics (QED) corrections. The results are compared with all existing experimental and theoretical data