New Treatment Options in Advanced Stage Follicular Lymphoma

Follicular lymphoma is one of the most common non-Hodgkin's lymphomas with an expected survival of more than 20 years for the majority of patients. This impressive outcome has been achieved with the introduction of immunochemotherapy, as first line treatment with remissions lasting over 8 years, followed by other treatment options at first or subsequent relapse. However, certain groups of patients still have a poor prognosis. In recent years the efficacy of chemotherapy regimens has been augmented by new compounds selectively targeting the cell surface, intracellular pathways, and/or the microenvironment. Some of these are beginning to change the therapeutic landscape. This review summarizes prognostic factors in follicular lymphoma in order to identify patients with greatest medical need for these new treatment options and reviews recent data from prospective clinical studies testing new agents in first-line and relapsed follicular lymphoma. Finally, we assess the current role of immunochemotherapy and discuss the requirements for future clinical trials

On Multifractal Structure in Non-Representational Art

Multifractal analysis techniques are applied to patterns in several abstract expressionist artworks, paintined by various artists. The analysis is carried out on two distinct types of structures: the physical patterns formed by a specific color (``blobs''), as well as patterns formed by the luminance gradient between adjacent colors (``edges''). It is found that the analysis method applied to ``blobs'' cannot distinguish between artists of the same movement, yielding a multifractal spectrum of dimensions between about 1.5-1.8. The method can distinguish between different types of images, however, as demonstrated by studying a radically different type of art. The data suggests that the ``edge'' method can distinguish between artists in the same movement, and is proposed to represent a toy model of visual discrimination. A ``fractal reconstruction'' analysis technique is also applied to the images, in order to determine whether or not a specific signature can be extracted which might serve as a type of fingerprint for the movement. However, these results are vague and no direct conclusions may be drawn.Comment: 53 pp LaTeX, 10 figures (ps/eps

Observation of the lowest energy gamma-ray in any superdeformed nucleus : 196Bi

New results on the superdeformed $^{196}$Bi nucleus a re reported. We have observed with the EUROBALL IV $\gamma$-ray spectrometer array a superdeformed trans ition of 124 keV which is the lowest observed energy $\gamma$-ray in any superdeformed nucleus. We have de velopped microscopic cranked Hartree-Fock-Bogoliubov calculations using the SLy4 effective force and a realistic surface p airing which strongly support the $K^\pi=2^-$($\pi$[651]1/2$\otimes \nu$[752]5/2) assignment of this su perdeformed band

Wake Development behind Paired Wings with Tip and Root Trailing Vortices: Consequences for Animal Flight Force Estimates

Recent experiments on flapping flight in animals have shown that a variety of unrelated species shed a wake behind left and right wings consisting of both tip and root vortices. Here we present an investigation using Particle Image Velocimetry (PIV) of the behaviour and interaction of trailing vortices shed by paired, fixed wings that simplify and mimic the wake of a flying animal with a non-lifting body. We measured flow velocities at five positions downstream of two adjacent NACA 0012 aerofoils and systematically varied aspect ratio, the gap between the wings (corresponding to the width of a non-lifting body), angle of attack, and the Reynolds number. The range of aspect ratios and Reynolds number where chosen to be relevant to natural fliers and swimmers, and insect flight in particular. We show that the wake behind the paired wings deformed as a consequence of the induced flow distribution such that the wingtip vortices convected downwards while the root vortices twist around each other. Vortex interaction and wake deformation became more pronounced further downstream of the wing, so the positioning of PIV measurement planes in experiments on flying animals has an important effect on subsequent force estimates due to rotating induced flow vectors. Wake deformation was most severe behind wings with lower aspect ratios and when the distance between the wings was small, suggesting that animals that match this description constitute high-risk groups in terms of measurement error. Our results, therefore, have significant implications for experimental design where wake measurements are used to estimate forces generated in animal flight. In particular, the downstream distance of the measurement plane should be minimised, notwithstanding the animal welfare constraints when measuring the wake behind flying animals

Biomechanics of predator–prey arms race in lion, zebra, cheetah and impala

The fastest and most manoeuvrable terrestrial animals are found in savannah habitats, where predators chase and capture running prey. Hunt outcome and success rate are critical to survival, so both predator and prey should evolve to be faster and/or more manoeuvrable. Here we compare locomotor characteristics in two pursuit predator–prey pairs, lion–zebra and cheetah–impala, in their natural savannah habitat in Botswana. We show that although cheetahs and impalas were universally more athletic than lions and zebras in terms of speed, acceleration and turning, within each predator–prey pair, the predators had 20% higher muscle fibre power than prey, 37% greater acceleration and 72% greater deceleration capacity than their prey. We simulated hunt dynamics with these data and showed that hunts at lower speeds enable prey to use their maximum manoeuvring capacity and favour prey survival, and that the predator needs to be more athletic than its prey to sustain a viable success rate

The life of the cortical column: opening the domain of functional architecture of the cortex

The concept of the cortical column refers to vertical cell bands with similar response properties, which were initially observed by Vernon Mountcastle’s mapping of single cell recordings in the cat somatic cortex. It has subsequently guided over 50 years of neuroscientific research, in which fundamental questions about the modularity of the cortex and basic principles of sensory information processing were empirically investigated. Nevertheless, the status of the column remains controversial today, as skeptical commentators proclaim that the vertical cell bands are a functionally insignificant by-product of ontogenetic development. This paper inquires how the column came to be viewed as an elementary unit of the cortex from Mountcastle’s discovery in 1955 until David Hubel and Torsten Wiesel’s reception of the Nobel Prize in 1981. I first argue that Mountcastle’s vertical electrode recordings served as criteria for applying the column concept to electrophysiological data. In contrast to previous authors, I claim that this move from electrophysiological data to the phenomenon of columnar responses was concept-laden, but not theory-laden. In the second part of the paper, I argue that Mountcastle’s criteria provided Hubel Wiesel with a conceptual outlook, i.e. it allowed them to anticipate columnar patterns in the cat and macaque visual cortex. I argue that in the late 1970s, this outlook only briefly took a form that one could call a ‘theory’ of the cerebral cortex, before new experimental techniques started to diversify column research. I end by showing how this account of early column research fits into a larger project that follows the conceptual development of the column into the present

Solvable model of a phase oscillator network on a circle with infinite-range Mexican-hat-type interaction

We describe a solvable model of a phase oscillator network on a circle with infinite-range Mexican-hat-type interaction. We derive self-consistent equations of the order parameters and obtain three non-trivial solutions characterized by the rotation number. We also derive relevant characteristics such as the location-dependent distributions of the resultant frequencies of desynchronized oscillators. Simulation results closely agree with the theoretical ones

Perceptual Context in Cognitive Hierarchies

Cognition does not only depend on bottom-up sensor feature abstraction, but also relies on contextual information being passed top-down. Context is higher level information that helps to predict belief states at lower levels. The main contribution of this paper is to provide a formalisation of perceptual context and its integration into a new process model for cognitive hierarchies. Several simple instantiations of a cognitive hierarchy are used to illustrate the role of context. Notably, we demonstrate the use context in a novel approach to visually track the pose of rigid objects with just a 2D camera

The UFM1 Pathway Impacts HCMV US2-Mediated Degradation of HLA Class I

To prevent accumulation of misfolded proteins in the endoplasmic reticulum, chaperones perform quality control on newly translated proteins and redirect misfolded proteins to the cytosol for degradation by the ubiquitin-proteasome system. This pathway is called ER-associated protein degradation (ERAD). The human cytomegalovirus protein US2 induces accelerated ERAD of HLA class I molecules to prevent immune recognition of infected cells by CD8(+) T cells. Using US2-mediated HLA-I degradation as a model for ERAD, we performed a genome-wide CRISPR/Cas9 library screen to identify novel cellular factors associated with ERAD. Besides the identification of known players such as TRC8, p97, and UBE2G2, the ubiquitin-fold modifier1 (UFM1) pathway was found to affect degradation of HLA-I. UFMylation is a post-translational modification resembling ubiquitination. Whereas we observe ubiquitination of HLA-I, no UFMylation was detected on HLA-I or several other proteins involved in degradation of HLA-I, suggesting that the UFM1 pathway impacts ERAD in a different manner than ubiquitin. Interference with the UFM1 pathway seems to specifically inhibit the ER-to-cytosol dislocation of HLA-I. In the absence of detectable UFMylation of HLA-I, UFM1 may contribute to US2-mediated HLA-I degradation by misdirecting protein sorting indirectly. Mass spectrometry analysis of US2-expressing cells showed that ribosomal proteins are a major class of proteins undergoing extensive UFMylation; the role of these changes in protein degradation may be indirect and remains to be established.This article belongs to the Special Issue Ubiquitin and Ubiquitin-Like Proteins: From Basic Mechanisms to Human Disorder