Ongoing trials in low-grade lymphoma

There are many therapies available for the management of low-grade lymphoma. With follicular lymphoma, for example, combination of chemotherapy and rituximab (immuno-chemotherapy) and consecutive maintenance therapy for 2 years is the current standard of care. To date, the most widely used regimen seems to be rituximab combined with cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). Substitution of liposomal doxorubicin in place of conventional doxorubicin may improve outcomes in this indication, although evidence for its use in low-grade lymphoma is not as relevant as in aggressive lymphoma. Bendamustine, in combination with rituximab, has shown very good efficacy and tolerability in several lymphoma types, particularly follicular lymphoma and other low-grade lymphomas. Other combinations, such as those including bortezomib and lenalidomide, are under investigation in low-grade lymphoma, and the duration of rituximab maintenance therapy following bendamustine-rituximab-containing induction is being researched by the German Study Group for Indolent Lymphoma (StiL)

The running kinematics of free-roaming giraffes, measured using a low cost unmanned aerial vehicle (UAV)

The study of animal locomotion can be logistically challenging, especially in the case of large or unhandleable animals in uncontrolled environments. Here we demonstrate the utility of a low cost unmanned aerial vehicle (UAV) in measuring two-dimensional running kinematics from free-roaming giraffes (Giraffa camelopardalis giraffa) in the Free State Province, South Africa. We collected 120 Hz video of running giraffes, and calibrated each video frame using metatarsal length as a constant object of scale. We tested a number of methods to measure metatarsal length. The method with the least variation used close range photography and a trigonometric equation to spatially calibrate the still image, and derive metatarsal length. In the absence of this option, a spatially calibrated surface model of the study terrain was used to estimate topographical dimensions in video footage of interest. Data for the terrain models were collected using the same equipment, during the same study period. We subsequently validated the accuracy of the UAV method by comparing similar speed measurements of a human subject running on a treadmill, with treadmill speed. At 8 m focal distance we observed an error of 8% between the two measures of speed. This error was greater at a shorter focal distance, and when the subject was not in the central field of view. We recommend that future users maximise the camera focal distance, and keep the subject in the central field of view. The studied giraffes used a grounded rotary gallop with a speed range of 3.4–6.9 ms−1 (never cantering, trotting or pacing), and lower duty factors when compared with other cursorial quadrupeds. As this pattern might result in adverse increases in peak vertical limb forces with speed, it was notable to find that contralateral limbs became more in-phase with speed. Considering the latter pattern and the modest maximal speed of giraffes, we speculate that tissue safety factors are maintained within tolerable bounds this way. Furthermore, the angular kinematics of the neck were frequently isolated from the pitching of the body during running; this may be a result of the large mass of the head and neck. Further field experiments and biomechanical models are needed to robustly test these speculations

Frame-semantic parsing

Frame semantics is a linguistic theory that has been instantiated for English in the FrameNet lexicon. We solve the problem of frame-semantic parsing using a two-stage statistical model that takes lexical targets (i.e., content words and phrases) in their sentential contexts and predicts frame-semantic structures. Given a target in context, the first stage disambiguates it to a semantic frame. This model uses latent variables and semi-supervised learning to improve frame disambiguation for targets unseen at training time. The second stage finds the target's locally expressed semantic arguments. At inference time, a fast exact dual decomposition algorithm collectively predicts all the arguments of a frame at once in order to respect declaratively stated linguistic constraints, resulting in qualitatively better structures than naïve local predictors. Both components are feature-based and discriminatively trained on a small set of annotated frame-semantic parses. On the SemEval 2007 benchmark data set, the approach, along with a heuristic identifier of frame-evoking targets, outperforms the prior state of the art by significant margins. Additionally, we present experiments on the much larger FrameNet 1.5 data set. We have released our frame-semantic parser as open-source software.United States. Defense Advanced Research Projects Agency (DARPA grant NBCH-1080004)National Science Foundation (U.S.) (NSF grant IIS-0836431)National Science Foundation (U.S.) (NSF grant IIS-0915187)Qatar National Research Fund (NPRP 08-485-1-083

Retail revolution and the village shop, c . 1660-1860

Village shops have been largely overlooked in the recent literature on British retailing in the eighteenth and nineteenth centuries, which has sought to redefine the parameters and timing of retail transformation. While urban shops have been explored in detail, often in ways that highlight their role in a parallel transformation in consumption patterns, little attempt has been made to look inside village shops or examine the character and practices of rural retailers. This article addresses this lacuna and offers fresh insights into the shifting position of village shops in these broader economic, business, and social changes. Taking a long view of the period c. 1660–1860, it draws on a wide range of sources to examine the stock sold and the degree of specialization exhibited by village shops, and the changing trading practices of village shopkeepers, including the provision of credit, the pricing of goods, and marketing activities. In doing so, the article highlights both long-term continuities and important innovations of the type that also characterize urban shops, and argues that village shops, while central to rural social and economic networks, were also intimately bound into broader retail systems

Heat Shock Protein HSP27 Secretion by Ovarian Cancer Cells Is Linked to Intracellular Expression Levels, Occurs Independently of the Endoplasmic Reticulum Pathway and HSP27’s Phosphorylation Status, and Is Mediated by Exosome Liberation

The heat shock protein HSP27 has been correlated in ovarian cancer (OC) patients with aggressiveness and chemoresistance and, therefore, represents a promising potential biomarker for OC diagnosis, prognosis, and treatment response. Notably, secretion of soluble HSP27 has been described by a few cell types and may take place as well in OC cells. Therefore, we studied HSP27 secretion mechanisms under diverse cellular conditions in an OC cell model system. Secretion of HSP27 was characterized after overexpression of HSP27 by transfected plasmids and after heat shock. Intra- and extracellular HSP27 amounts were assessed by Western blotting and ELISA. Protein secretion was blocked by brefeldin A and the impact of the HSP27 phosphorylation status was analyzed overexpressing HSP27 phosphomutants. The present study demonstrated that HSP27 secretion by OVCAR-3 and SK-OV-3 cells depends on intracellular HSP27 concentrations. Moreover, HSP27 secretion is independent of the endoplasmic reticulum secretory pathway and HSP27 phosphorylation. Notably, analysis of OC cell-born exosomes not only confirmed the concentration-dependent correlation of HSP27 expression and secretion but also demonstrated a concentration-dependent incorporation of HSP27 protein into exosomes. Thus, secreted HSP27 may become more important as an extracellular factor which controls the tumor microenvironment and might be a noninvasive biomarker