Complement deficiencies limit CD20 monoclonal antibody treatment efficacy in CLL

Monoclonal antibodies (MAbs) form a central part of chronic lymphocytic leukaemia (CLL) treatment. We therefore evaluated whether complement defects in CLL patients reduced the induction of complement-dependent cytotoxicity (CDC) by using anti-CD20 MAbs rituximab (RTX) and ofatumumab (OFA). Ofatumumab elicited higher CDC levels than RTX in all CLL samples examined, particularly in poor prognosis cohorts (11q− and 17p−). Serum sample analyses revealed that 38.1% of patients were deficient in one or more complement components, correlating with reduced CDC responses. Although a proportion of patients with deficient complement levels initially induced high levels of CDC, on secondary challenge CDC activity in sera was significantly reduced, compared with that in normal human serum (NHS; P<0.01; n=52). In addition, a high CLL cell number contributed to rapid complement exhaustion. Supplementing CLL serum with NHS or individual complement components, particularly C2, restored CDC on secondary challenge to NHS levels (P<0.0001; n=9). In vivo studies revealed that complement components were exhausted in CLL patient sera post RTX treatment, correlating with an inability to elicit CDC. Supplementing MAb treatment with fresh-frozen plasma may therefore maintain CDC levels in CLL patients with a complement deficiency or high white blood cell count. This study has important implications for CLL patients receiving anti-CD20 MAb therapy

Ocular structure in vitamin A deficiency in the monkey

1. The role of vitamin A in the metabolism of cone cells of the retina was investigated, from the morphological angle, by studying their structure in induced deficiency of vitamin A in three monkeys. 2. Unequivocal signs of structural damage were observed in the cone and rod cells of the deficient animals, which also showed the classical signs of vitamin A deficiency in other organs. 3. In vitamin A deficiency, damage to the visual cell layer of the retina occurred in one monkey in the absence of corneal involvement. This finding suggests that chronic vitamin A deficiency in the community may lead to progressive damage to the visual cells in a much larger number of persons than the incidence figures for keratomalacia indicate. 4. Degeneration of pigment epithelium was present in retinal sections from all the deficient animals. The possible role of the pigment epithelium in the pathogenesis of the visual defect in vitamin A deficiency has been discussed. 5. Degenerative changes were noted in Descemet's endothelium. This damage may contribute to the degeneration of the corneal epithelium

Nodular lymphocyte predominant Hodgkin lymphoma behaves as a distinct clinical entity with good outcome: evidence from 14-year followup in the West of Scotland Cancer Network

Clinically and biologically, nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) has much more in common with germinal-center derived B-cell non-Hodgkin lymphoma (NHL) than with classical Hodgkin lymphoma (cHL). Management of NLPHL remains controversial. In a 14-year multicenter series, 69 cases were analyzed, and the median follow-up was 53 months (range 11–165.) B-symptoms were present in only 4.3% of patients, and 81.1% of patients had stage I/II disease. Treatment was with radiotherapy (53.6%), chemotherapy (21.7%), combined modality (17.4%), and observation (7.2%). In all, 10.1% of patients relapsed and 2.9% of patients developed high-grade transformation to DLBCL. All relapses and transformations were salvageable. No patient died of their disease. The 5-year relapse-free survival was 92%, transformation-free survival 98.4%, and overall survival 100%. We conclude that NLPHL behaves as a distinct clinical entity, often presenting at an early stage without risk factors. It has an excellent outcome. It may be possible, in early-stage disease, to reduce the intensity of therapy in NLPHL, to single-modality radiotherapy, without affecting OS

Unitary relations in time-dependent harmonic oscillators

For a harmonic oscillator with time-dependent (positive) mass and frequency, an unitary operator is shown to transform the quantum states of the system to those of a harmonic oscillator system of unit mass and time-dependent frequency, as well as operators. For a driven harmonic oscillator, it is also shown that, there are unitary transformations which give the driven system from the system of same mass and frequency without driving force. The transformation for a driven oscillator depends on the solution of classical equation of motion of the driven system. These transformations, thus, give a simple way of finding exact wave functions of a driven harmonic oscillator system, provided the quantum states of the corresponding system of unit mass are given.Comment: Submitted to J. Phys.

Analytic Behaviour of Competition among Three Species

We analyse the classical model of competition between three species studied by May and Leonard ({\it SIAM J Appl Math} \textbf{29} (1975) 243-256) with the approaches of singularity analysis and symmetry analysis to identify values of the parameters for which the system is integrable. We observe some striking relations between critical values arising from the approach of dynamical systems and the singularity and symmetry analyses.Comment: 14 pages, to appear in Journal of Nonlinear Mathematical Physic

Lie symmetries for two-dimensional charged particle motion

We find the Lie point symmetries for non-relativistic two-dimensional charged particle motion. These symmetries comprise a quasi-invariance transformation, a time-dependent rotation, a time-dependent spatial translation and a dilation. The associated electromagnetic fields satisfy a system of first-order linear partial differential equations. This system is solved exactly, yielding four classes of electromagnetic fields compatible with Lie point symmetries

Ultrafast decay of hot phonons in an AlGaN/AlN/AlGaN/GaN camelback channel

A bottleneck for heat dissipation from the channel of a GaN-based heterostructure field-effect transistor is treated in terms of the lifetime of nonequilibrium (hot) longitudinal optical phonons, which are responsible for additional scattering of electrons in the voltage-biased quasi-two-dimensional channel. The hot-phonon lifetime is measured for an Al0.33Ga0.67N/AlN/Al0.1Ga0.9N/GaN heterostructure where the mobile electrons are spread in a composite Al0.1Ga0.9N/GaN channel and form a camelback electron density profile at high electric fields. In accordance with plasmon-assisted hot-phonon decay, the parameter of importance for the lifetime is not the total charge in the channel (the electron sheet density) but rather the electron density profile. This is demonstrated by comparing two structures with equal sheet densities (1 × 1013 cm−2), but with different density profiles. The camelback channel profile exhibits a shorter hot-phonon lifetime of ∼270 fs as compared with ∼500 fs reported for a standard Al0.33Ga0.67N/AlN/GaN channel at low supplied power levels. When supplied power is sufficient to heat the electrons \u3e 600 K, ultrafast decay of hot phonons is observed in the case of the composite channel structure. In this case, the electron density profile spreads to form a camelback profile, and hot-phonon lifetime reduces to ∼50 fs

Symmetry dependence of phonon lineshapes in superconductors with anisotropic gaps

The temperature dependence below $T_{c}$ of the lineshape of optical phonons of different symmetry as seen in Raman scattering is investigated for superconductors with anisotropic energy gaps. It is shown that the symmetry of the electron-phonon vertex produces non-trivial couplings to an anisotropic energy gap which leads to unique changes in the phonon lineshape for phonons of different symmetry. The phonon lineshape is calculated in detail for $B_{1g}$ and $A_{1g}$ phonons in a superconductor with $d_{x^{2}-y^{2}}$ pairing symmetry. The role of satellite peaks generated by the electron-phonon coupling are also addressed. The theory accounts for the substantial phonon narrowing of the $B_{1g}$ phonon, while narrowing of the $A_{1g}$ phonon which is indistinguishable from the normal state is shown, in agreement with recent measurements on BSCCO.Comment: 15 pages (3 Figures available upon request), Revtex, 1

Electrically and magnetically tunable phase shifters based on a barium strontium titanate-yttrium iron garnet layered structure

We report on the tuning of permittivity and permeability of a ferroelectric/ferromagnetic bilayer structure which can be used as a microwavephase shifter with two degrees of tuning freedom. The structure was prepared by the growth of a yttrium iron garnet (YIG) layer on a gadolinium gallium garnet substrate by liquid phase epitaxy, the growth of a barium strontium titanate (BST) layer on the YIG layer through pulsed laser deposition, and then the fabrication of a coplanar waveguide on the top of BST through e-beam evaporation and trilayer liftoff techniques. The phase shifters exhibit a differential phase shift of 38°/cm at 6 GHz through permittivity tuning under an applied electric field of ∼75 kV/cm and a static magnetic field of 1700 Oe. By tuning the permeability through the applied magnetic field we increase the differential phase shift to 52°/cm and simultaneously obtain a better match to the zero applied electric field condition, resulting in an improvement in the return loss from 22.4 to 24.9 dB. Additionally, we demonstrate the use of a lead magnesium niobate-lead titanate (PMN-PT) layer to tune the permeability of the YIG layer. This tuning relies on the piezoelectric and magnetostrictive effects of PMN-PT and YIG, respectively. Tuning of the ferromagnetic response through strain and magnetostriction as opposed to applied magnetic field can potentially pave the way for low power consumption, continuously and rapidly tunable, impedance matched phase shifters

Camelback channel for fast decay of LO phonons in GaN heterostructure field-effect transistor at high electron density

Fluctuation technique is used to measure hot-phonon lifetime in dual channel GaN-based configuration proposed to support high-power operation at high frequencies. The channel is formed of a composite Al0.1Ga0.9N/GaN structure situated in an Al0.82In0.18N/AlN/Al0.1Ga0.9N/GaN heterostructure. According to capacitance–voltage measurements and simultaneous treatment of Schrödinger–Poisson equations, the mobile electrons in this dual channel configuration form a camelback density profile at elevated hot-electron temperatures. The hot-phonon lifetime was found to depend on the shape of the electron profile rather than solely on its sheet density. The camelback channel with an electron sheet density of 1.8 × 1013 cm−2 demonstrates ultrafast decay of hot phonons at hot-electron temperatures above 600 K: the hot-phonon lifetime is below ∼60 fs in contrast to ∼600 fs at an electron sheet density of 1.2 × 1013 cm−2 obtained in a reference Al0.82In0.18N/AlN/GaN structure at 600 K. The results suggest a suitable method to increase the electron sheet density without the deleterious effect caused by inefficient hot-phonon decay observed in a standard design at similar electron densities