29 research outputs found
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The Dawn of Crowdfarms
Some small companies are making crowdwork part of their formal business via teams that can complete multifaceted, complex tasks requiring specialized expertise
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Tasks of a Different Color: How Crowdsourcing Practices Differ per Complex Task Type and Why This Matters
Crowdsourcing in China is a thriving industry. Among its most interesting structures, we find crowdfarms, in which crowdworkers self-organize as small organizations to tackle macrotasks. Little, however, is known as to which practices these crowdfarms use to tackle the macrotasks, and this goes hand in hand with the current practice of the HCI research community to treat all forms of complex crowdsourcing work as practically the same. However, macrotasks differ substantially regarding structure and decomposability. Treating them under one umbrella term - macrotasking - can lead to an imprecise understanding of the workforce involved. We address this gap by examining the work practices of 31 Chinese crowdfarms on the four main macrotask types, namely: modular, interlaced, wicked, and container macrotasks. Our results confirm essential differences in how these nascent crowd organizations address different macrotasks and shed light on what platforms can do to improve the uptake of such work
The impact of using assimilated Aeolus wind data on regional WRF-Chem dust simulations
Landâatmosphere interactions govern the process of dust emission and transport. An accurate depiction of these physical processes within numerical weather prediction models allows for better estimating the spatial and temporal distribution of the dust burden and the characterisation of source and recipient areas. In the presented study, the ECMWF-IFS (European Centre for Medium-Range Weather Forecast â Integrated Forecasting System) outputs, produced with and without the assimilation of Aeolus quality-assured Rayleighâclear and Mieâcloudy horizontal line-of-sight wind profiles, are used as initial or boundary conditions in the Weather Research and Forecasting model coupled with Chemistry (WRF-Chem) to simulate 2-month periods in the spring and autumn of 2020, focusing on a case study in October. The experiments have been performed over the broader eastern Mediterranean and Middle East (EMME) region, which is frequently subjected to dust transport, as it encompasses some of the most active erodible dust sources. Aerosol- and dust-related model outputs (extinction coefficient, optical depth and concentrations) are qualitatively and quantitatively evaluated against ground- and satellite-based observations. Ground-based columnar and vertically resolved aerosol optical properties are acquired through AERONET sun photometers and PollyXT lidar, while near-surface concentrations are taken from EMEP. Satellite-derived vertical dust and columnar aerosol optical properties are acquired through LIVAS (LIdar climatology of Vertical Aerosol Structure) and MIDAS (ModIs Dust AeroSol), respectively.
Overall, in cases of either high or low aerosol loadings, the model predictive skill is improved when WRF-Chem simulations are initialised with the meteorological fields of Aeolus wind profiles assimilated by the IFS. The improvement varies in space and time, with the most significant impact observed during the autumn months in the study region. Comparison with observation datasets saw a remarkable improvement in columnar aerosol optical depths, vertically resolved dust mass concentrations and near-surface particulate concentrations in the assimilated run against the control run. Reductions in model biases, either positive or negative, and an increase in the correlation between simulated and observed values was achieved for October 2020.</p
Identification of unique neoantigen qualities in long-term survivors of pancreatic cancer
Pancreatic ductal adenocarcinoma is a lethal cancer with fewer than 7% of patients surviving past 5 years. T-cell immunity has been linked to the exceptional outcome of the few long-term survivors1,2, yet the relevant antigens remain unknown. Here we use genetic, immunohistochemical and transcriptional immunoprofiling, computational biophysics, and functional assays to identify T-cell antigens in long-term survivors of pancreatic cancer. Using whole-exome sequencing and in silico neoantigen prediction, we found that tumours with both the highest neoantigen number and the most abundant CD8+ T-cell infiltrates, but neither alone, stratified patients with the longest survival. Investigating the specific neoantigen qualities promoting T-cell activation in long-term survivors, we discovered that these individuals were enriched in neoantigen qualities defined by a fitness model, and neoantigens in the tumour antigen MUC16 (also known as CA125). A neoantigen quality fitness model conferring greater immunogenicity to neoantigens with differential presentation and homology to infectious disease-derived peptides identified long-term survivors in two independent datasets, whereas a neoantigen quantity model ascribing greater immunogenicity to increasing neoantigen number alone did not. We detected intratumoural and lasting circulating T-cell reactivity to both high-quality and MUC16 neoantigens in long-term survivors of pancreatic cancer, including clones with specificity to both high-quality neoantigens and predicted cross-reactive microbial epitopes, consistent with neoantigen molecular mimicry. Notably, we observed selective loss of high-quality and MUC16 neoantigenic clones on metastatic progression, suggesting neoantigen immunoediting. Our results identify neoantigens with unique qualities as T-cell targets in pancreatic ductal adenocarcinoma. More broadly, we identify neoantigen quality as a biomarker for immunogenic tumours that may guide the application of immunotherapies
Targeting DNA Damage Response and Replication Stress in Pancreatic Cancer
Background and aims:
Continuing recalcitrance to therapy cements pancreatic cancer (PC) as the most lethal malignancy, which is set to become the second leading cause of cancer death in our society. The study aim was to investigate the association between DNA damage response (DDR), replication stress and novel therapeutic response in PC to develop a biomarker driven therapeutic strategy targeting DDR and replication stress in PC.
Methods:
We interrogated the transcriptome, genome, proteome and functional characteristics of 61 novel PC patient-derived cell lines to define novel therapeutic strategies targeting DDR and replication stress. Validation was done in patient derived xenografts and human PC organoids.
Results:
Patient-derived cell lines faithfully recapitulate the epithelial component of pancreatic tumors including previously described molecular subtypes. Biomarkers of DDR deficiency, including a novel signature of homologous recombination deficiency, co-segregates with response to platinum (P < 0.001) and PARP inhibitor therapy (P < 0.001) in vitro and in vivo. We generated a novel signature of replication stress with which predicts response to ATR (P < 0.018) and WEE1 inhibitor (P < 0.029) treatment in both cell lines and human PC organoids. Replication stress was enriched in the squamous subtype of PC (P < 0.001) but not associated with DDR deficiency.
Conclusions:
Replication stress and DDR deficiency are independent of each other, creating opportunities for therapy in DDR proficient PC, and post-platinum therapy
DNA methylation patterns identify subgroups of pancreatic neuroendocrine tumors with clinical association
Here we report the DNA methylation profile of 84 sporadic pancreatic neuroendocrine tumors (PanNETs) with associated clinical and genomic information. We identified three subgroups of PanNETs, termed T1, T2 and T3, with distinct patterns of methylation. The T1 subgroup was enriched for functional tumors and ATRX, DAXX and MEN1 wild-type genotypes. The T2 subgroup contained tumors with mutations in ATRX, DAXX and MEN1 and recurrent patterns of chromosomal losses in half of the genome with no association between regions with recurrent loss and methylation levels. T2 tumors were larger and had lower methylation in the MGMT gene body, which showed positive correlation with gene expression. The T3 subgroup harboured mutations in MEN1 with recurrent loss of chromosome 11, was enriched for grade G1 tumors and showed histological parameters associated with better prognosis. Our results suggest a role for methylation in both driving tumorigenesis and potentially stratifying prognosis in PanNETs
A case study on the importance of belief state representation for dialogue policy management
A key component of task-oriented dialogue systems is the belief state representation, since it directly affects the policy learning efficiency. In this paper, we propose a novel, binary, compact, yet scalable belief state representation. We compare the stan- dard verbose belief state representation (268 dimensions) with the domain-independent representation (57 dimensions) and the proposed representation (13 or 4 dimensions). To test those representations, the recently introduced Advantage Actor Critic (A2C) algorithm is exploited. The latter has not been tested before for any representation apart from the verbose one. We study the effect of the belief state representation within A2C un- der 0%, 15%, 30%, and 45% semantic error rate and conclude that the novel binary representation in general outperforms both the domain-independent and the verbose belief state represen- tation. Further, the robustness of the binary representation is tested under more realistic scenarios with mismatched semantic error rates, within the A2C and DQN algorithms. The results indicate that the proposed compact, binary representation per- forms better or similarly to the other representations, being an efficient and promising alternative to the full belief
Effect of intra-articular infliximab on synovial membrane pathology in a patient with a seronegative spondyloarthropathy
Objective: To demonstrate the efficacy of intra-articular infliximab in a patient with a persistent monarthritis who had previously had two arthroscopic synovectomies with limited success, and to determine the effect of intra-articular infliximab on synovial membrane pathology Method: Arthroscopic synovial biopsy specimens were collected before and after treatment with intra-articular infliximab. The synovial tissue was stained for a range of inflammatory cell subsets, cell adhesion molecules and cytokines using immunohistochemical techniques and quantified using digital image analysis and a semiquantitative scoring method. Results: Clinical improvement in the knee synovitis was seen after the first two intra-articular infliximab treatments, with a sustained clinical remission lasting for more than 12 months after the third treatment. Significant changes in cellular infiltration and expression of cytokines and cell adhesion molecules occurred as a result of treatment with intra-articular infliximab, with a reduction in some but not all cells in the inflammatory infiltrate, as well as a reduction in the expression of cell adhesion molecules (intercellular adhesion molecule-1 and vascular adhesion molecule-1) and production of cytokines (interleukin 1ÎČ and tumour necrosis factor α). Conclusion: Intra-articular infliximab administration is a viable treatment for a persistent monarthritis resistant to other treatment options and can successfully modulate the inflammatory milieu within the synovial membrane.M J Ahern, D G Campbell, H Weedon, V Papangelis, M D Smit
User-elicited dual-hand interactions for manipulating 3D objects in virtual reality environments
© 2018, The Author(s). Virtual reality technologies (VR) have advanced rapidly in the last few years. Prime examples include the Oculus RIFT and HTC Vive that are both head-worn/mounted displays (HMDs). VR HMDs enable a sense of immersion and allow enhanced natural interaction experiences with 3D objects. In this research we explore suitable interactions for manipulating 3D objects when users are wearing a VR HMD. In particular, this research focuses on a user-elicitation study to identify natural interactions for 3D manipulation using dual-hand controllers, which have become the standard input devices for VR HMDs. A user elicitation study requires potential users to provide interactions that are natural and intuitive based on given scenarios. The results of our study suggest that users prefer interactions that are based on shoulder motions (e.g., shoulder abduction and shoulder horizontal abduction) and elbow flexion movements. In addition, users seem to prefer one-hand interaction, and when two hands are required they prefer interactions that do not require simultaneous hand movements, but instead interactions that allow them to alternate between their hands. Results of our study are applicable to the design of dual-hand interactions with 3D objects in a variety of virtual reality environments