Anticancer Therapy SMRT-ens Up: Targeting the BCL6-SMRT Interaction in B Cell Lymphoma

Transcription factors have proven to be difficult targets for the development of small-molecule drugs. In this issue of Cancer Cell, Cerchietti et al. identify and characterize a specific, small-molecule inhibitor of BCL6, an oncogenic transcriptional repressor, that has high clinical promise for treating diffuse large B cell lymphoma

Fronto-striatal cognitive deficits at different stages of Parkinson's disease

Groups of patients with idiopathic Parkinson's disease, either medicated or unmedicated, were compared with matched groups of normal controls on a computerized battery previously shown to be sensitive to frontal lobe dysfunction, including tests of planning, spatial working memory and attentional set-shifting. In a series of problems based on the 'Tower of London' test, medicated patients with Parkinson's disease were shown to be impaired in the amount of time spent thinking about (planning) the solution to each problem. Additionally, an impairment in terms of the accuracy of the solution produced on this test was only evident in those patients with more severe clinical symptoms and was accompanied by deficits in an associated test of spatial short-term memory. Medicated patients with both mild and severe clinical symptoms were also impaired on a related test of spatial working memory. In contrast, a group of patients who were unmedicated and 'early in the course' of the disease were unimpaired in all three of these tests. However, all three Parkinson's disease groups were impaired in the test of attentional set-shifting ability, although unimpaired in a test of pattern recognition which is insensitive to frontal lobe damage. These data are compared with those previously published from a group of young neurosurgical patients with localized excisions of the frontal lobes and are discussed in terms of the specific nature of the cognitive deficit at different stages of Parkinson's disease

ADVISE: Symbolism and External Knowledge for Decoding Advertisements

In order to convey the most content in their limited space, advertisements embed references to outside knowledge via symbolism. For example, a motorcycle stands for adventure (a positive property the ad wants associated with the product being sold), and a gun stands for danger (a negative property to dissuade viewers from undesirable behaviors). We show how to use symbolic references to better understand the meaning of an ad. We further show how anchoring ad understanding in general-purpose object recognition and image captioning improves results. We formulate the ad understanding task as matching the ad image to human-generated statements that describe the action that the ad prompts, and the rationale it provides for taking this action. Our proposed method outperforms the state of the art on this task, and on an alternative formulation of question-answering on ads. We show additional applications of our learned representations for matching ads to slogans, and clustering ads according to their topic, without extra training.Comment: To appear, Proceedings of the European Conference on Computer Vision (ECCV

Poincar\'e Invariant Quantum Field Theories With Twisted Internal Symmetries

Following up the work of [1] on deformed algebras, we present a class of Poincar\'e invariant quantum field theories with particles having deformed internal symmetries. The twisted quantum fields discussed in this work satisfy commutation relations different from the usual bosonic/fermionic commutation relations. Such twisted fields by construction are nonlocal in nature. Despite this nonlocality we show that it is possible to construct local interaction Hamiltonians which satisfy cluster decomposition principle and are Lorentz invariant. We further illustrate these ideas by considering global SU(N) symmetries. Specifically we show that twisted internal symmetries can significantly simplify the discussion of the marginal deformations (\beta-deformations) of the N=4 SUSY theories.Comment: 27 pages, Typos Corrected, Text and Conclusions Unchanged, Version published in JHE

Born-Regulated Gravity in Four Dimensions

Previous work involving Born-regulated gravity theories in two dimensions is extended to four dimensions. The action we consider has two dimensionful parameters. Black hole solutions are studied for typical values of these parameters. For masses above a critical value determined in terms of these parameters, the event horizon persists. For masses below this critical value, the event horizon disappears, leaving a ``bare mass'', though of course no singularity.Comment: LaTeX, 15 pages, 2 figure

A common cardiac sodium channel variant associated with sudden infant death in African Americans, SCN5A S1103Y.

Thousands die each year from sudden infant death syndrome (SIDS). Neither the cause nor basis for varied prevalence in different populations is understood. While 2 cases have been associated with mutations in type Valpha, cardiac voltage-gated sodium channels (SCN5A), the "Back to Sleep" campaign has decreased SIDS prevalence, consistent with a role for environmental influences in disease pathogenesis. Here we studied SCN5A in African Americans. Three of 133 SIDS cases were homozygous for the variant S1103Y. Among controls, 120 of 1,056 were carriers of the heterozygous genotype, which was previously associated with increased risk for arrhythmia in adults. This suggests that infants with 2 copies of S1103Y have a 24-fold increased risk for SIDS. Variant Y1103 channels were found to operate normally under baseline conditions in vitro. As risk factors for SIDS include apnea and respiratory acidosis, Y1103 and wild-type channels were subjected to lowered intracellular pH. Only Y1103 channels gained abnormal function, demonstrating late reopenings suppressible by the drug mexiletine. The variant appeared to confer susceptibility to acidosis-induced arrhythmia, a gene-environment interaction. Overall, homozygous and rare heterozygous SCN5A missense variants were found in approximately 5% of cases. If our findings are replicated, prospective genetic testing of SIDS cases and screening with counseling for at-risk families warrant consideration

Decomposition of coarse woody debris in a long-term litter manipulation experiment: A focus on nutrient availability

The majority of above-ground carbon in tropical forests is stored in wood, which is returned to the atmosphere during decomposition of coarse woody debris. However, the factors controlling wood decomposition have not been experimentally manipulated over time scales comparable to the length of this process.We hypothesized that wood decomposition is limited by nutrient availability and tested this hypothesis in a long-term litter addition and removal experiment in a lowland tropical forest in Panama. Specifically, we quantified decomposition using a 15-year chronosequence of decaying boles, and measured respiration rates and nutrient limitation of wood decomposer communities.The long-term probability that a dead tree completely decomposed was decreased in plots where litter was removed, but did not differ between litter addition and control treatments. Similarly, respiration rates of wood decomposer communities were greater in control treatments relative to litter removal plots; litter addition treatments did not differ from either of the other treatments. Respiration rates increased in response to nutrient addition (nitrogen, phosphorus, and potassium) in the litter removal and addition treatments, but not in the controls.Established decreases in concentrations of soil nutrients in litter removal plots and increased respiration rates in response to nutrient addition suggest that reduced rates of wood decomposition after litter removal were caused by decreased nutrient availability. The effects of litter manipulations differed directionally from a previous short-term decomposition study in the same plots, and reduced rates of bole decomposition in litter removal plots did not emerge until after more than 6 years of decomposition. These differences suggest that litter-mediated effects on nutrient dynamics have complex interactions with decomposition over time