Current directions in the treatment of classical Hodgkin lymphoma

Optimal management of patients who present with Hodgkin lymphoma continues to evolve. Most patients are cured with current treatment strategies, some but both short and long-term morbidity and mortality from treatment have particular relevance given the youth of the patient population. Combininations of targeted agents together with conventional chemotherapy have recently been investigated in phase 3 cliniial trials for advanced-stage Hodkgkin lymphoma, and have demonstrated improved efficacy compared with chemotherapy alone. These include both antibody-drug conjugates and PD-1 blockade. Treatment approaches have historically differed between pediatric and adult groups, but recent collaborations between adullt and pediatric groups via the NCTN mechanism have resulted in the successful completion of enrollment in an advanced-stage Hodgkin lymphoma and the opening of an early-stage trial that will enroll patients accross a broad age spectrum. Novel approachs incorporating targeted and immunomodulatory agents in the relapse setting are being actively investagated in the relapse setting as well

Lattice Effects in Crystal Evaporation

We study the dynamics of a stepped crystal surface during evaporation, using the classical model of Burton, Cabrera and Frank, in which the dynamics of the surface is represented as a motion of parallel, monoatomic steps. The validity of the continuum approximation treated by Frank is checked against numerical calculations and simple, qualitative arguments. The continuum approximation is found to suffer from limitations related, in particular, to the existence of angular points. These limitations are often related to an adatom detachment rate of adatoms which is higher on the lower side of each step than on the upper side ("Schwoebel effect").Comment: DRFMC/SPSMS/MDN, Centre d'Etudes Nucleaires de Grenoble, 25 pages, LaTex, revtex style. 8 Figures, available upon request, report# UBFF30119

Is keV ion induced pattern formation on Si(001) caused by metal impurities?

We present ion beam erosion experiments performed in ultra high vacuum using a differentially pumped ion source and taking care that the ion beam hits the Si(001) sample only. Under these conditions no ion beam patterns form on Si for angles below 45 degrees with respect to the global surface normal using 2 keV Kr ions and fluences of 2 x 10^22 ions/m^2. In fact, the ion beam induces a smoothening of preformed patterns. Simultaneous sputter deposition of stainless steel in this angular range creates a variety of patterns, similar to those previously ascribed to clean ion beam induced destabilization of the surface profile. Only for grazing incidence with incident angles between 60 degrees and 83 degrees pronounced ion beam patterns form. It appears that the angular dependent stability of Si(001) against pattern formation under clean ion beam erosion conditions is related to the angular dependence of the sputtering yield, and not primarily to a curvature dependent yield as invoked frequently in continuum theory models.Comment: 15 pages, 7 figures. This is an author-created, un-copyedited version of an article published in Nanotechnology. IOP Publishing Ltd is not responsible for any errors or omissions in this version of the manuscript or any version derived from i

Band Formation during Gaseous Diffusion in Aerogels

We study experimentally how gaseous HCl and NH_3 diffuse from opposite sides of and react in silica aerogel rods with porosity of 92 % and average pore size of about 50 nm. The reaction leads to solid NH_4Cl, which is deposited in thin sheet-like structures. We present a numerical study of the phenomenon. Due to the difference in boundary conditions between this system and those usually studied, we find the sheet-like structures in the aerogel to differ significantly from older studies. The influence of random nucleation centers and inhomogeneities in the aerogel is studied numerically.Comment: 7 pages RevTex and 8 figures. Figs. 4-8 in Postscript, Figs. 1-3 on request from author

Fine structure, magnetic field and heating of sunspot penumbrae

We interpret penumbral filaments as due to convection in field-free, radially aligned gaps just below the visible surface of the penumbra, intruding into a nearly potential field above. This solves the classical discrepancy between the large heat flux and the low vertical velocities observed in the penumbra. The presence of the gaps causes strong small-scale fluctuations in inclination, azimuth angle and field strength, but without strong forces acting on the gas. The field is nearly horizontal in a region around the cusp-shaped top of the gap, thereby providing an environment for Evershed flows. We identify this region with the recently discovered dark penumbral cores. Its darkness has the same cause as the dark lanes in umbral light-bridges, reproduced in numerical simulations by Nordlund and Stein (2005). We predict that the large vertical and horizontal gradients of the magnetic field inclination and azimuth in the potential field model will produce the net circular polarization seen in observations. The model also explains the significant elevation of bright filaments above their surroundings. It predicts that dark areas in the penumbra are of two different kinds: dark filament cores containing the most inclined (horizontal) fields, and regions between bright filaments, containing the least inclined field lines.Comment: submitted to A&

Physical Aspects of Axonemal Beating and Swimming

We discuss a two-dimensional model for the dynamics of axonemal deformations driven by internally generated forces of molecular motors. Our model consists of an elastic filament pair connected by active elements. We derive the dynamic equations for this system in presence of internal forces. In the limit of small deformations, a perturbative approach allows us to calculate filament shapes and the tension profile. We demonstrate that periodic filament motion can be generated via a self-organization of elastic filaments and molecular motors. Oscillatory motion and the propagation of bending waves can occur for an initially non-moving state via an instability termed Hopf bifurcation. Close to this instability, the behavior of the system is shown to be independent of microscopic details of the axoneme and the force-generating mechanism. The oscillation frequency however does depend on properties of the molecular motors. We calculate the oscillation frequency at the bifurcation point and show that a large frequency range is accessible by varying the axonemal length between 1 and 50$\mu$m. We calculate the velocity of swimming of a flagellum and discuss the effects of boundary conditions and externally applied forces on the axonemal oscillations.Comment: 14 pages, 8 figures, REVTE

Embodied cognitive ecosophy: the relationship of mind, body, meaning and ecology

The concept of embodied cognition has had a major impact in a number of disciplines. The extent of its consequences on general knowledge and epistemology are still being explored. Embodied cognition in human geography has its own traditions and discourses but these have become somewhat isolated in the discipline itself. This paper argues that findings in other disciplines are of value in reconceptualising embodied cognition in human geography and this is explored by reconsidering the concept of ecosophy. Criticisms of ecosophy as a theory are considered and recent work in embodied cognition is applied to consider how such criticisms might be addressed. An updated conceptualisation is proposed, the embodied cognitive ecosophy, and three characteristics arising from this criticism and synthesis are presented with a view to inform future discussions of ecosophy and emotional geography

Human PrimPol is a highly error-prone polymerase regulated by single-stranded DNA binding proteins

PrimPol is a recently identified polymerase involved in eukaryotic DNA damage tolerance, employed in both re-priming and translesion synthesis mechanisms to bypass nuclear and mitochondrial DNA lesions. In this report, we investigate how the enzymatic activities of human PrimPol are regulated. We show that, unlike other TLS polymerases, PrimPol is not stimulated by PCNA and does not interact with it in vivo. We identify that PrimPol interacts with both of the major single-strand binding proteins, RPA and mtSSB in vivo. Using NMR spectroscopy, we characterize the domains responsible for the PrimPol-RPA interaction, revealing that PrimPol binds directly to the N-terminal domain of RPA70. In contrast to the established role of SSBs in stimulating replicative polymerases, we find that SSBs significantly limit the primase and polymerase activities of PrimPol. To identify the requirement for this regulation, we employed two forward mutation assays to characterize PrimPol's replication fidelity. We find that PrimPol is a mutagenic polymerase, with a unique error specificity that is highly biased towards insertion-deletion errors. Given the error-prone disposition of PrimPol, we propose a mechanism whereby SSBs greatly restrict the contribution of this enzyme to DNA replication at stalled forks, thus reducing the mutagenic potential of PrimPol during genome replication

Comparison of the TESLA, NLC and CLIC Beam Collimation Systems Performance

This note describes studies performed in the framework of the Collimation task Force organized to support work of the International Linear Collider Technical Review Committee aiming in comparison of performance of the post-linac beam collimation systems in TESLA, JLC/NLC and CLIC linear collider designs. Collimation of the beam halo and synchrotron radiation collimation have been compared for all projects using the same computer code and same assumptions. It is shown that though the performance of the presently designed systems differ, and not always correspond to expected performance, achieving required performance in the future collider is feasible. Furthe, post-TRC plans of the Collimation task Force are discussed as well

Super AutoDipole

The publicly available package for an automated dipole subtraction, AutoDipole, is extended to include the SUSY dipoles in the MSSM. All fields in the SM and the MSSM are available. The code is checked against the analytical expressions for a simple process. The extended package makes it possible to compute the QCD NLO corrections to SUSY multi-parton processes like the stop pair production plus jets at the LHC.Comment: 16 pages, 1 figure, v2: a few typos to match the published version in Eur. Phys. J.