Drug accumulation into single drug-sensitive and drug-resistant prostate cancer cells conducted on the single cell bioanalyzer

Multidrug resistance (MDR) occurs in prostate cancer, and this happens when the cancer cells resist chemotherapeutic drugs by pumping them out of the cells. MDR inhibitors such as cyclosporin A (CsA) can stop the pumping and enhance the drugs accumulated in the cells. The cellular drug accumulation is monitored using a microfluidic chip mounted on a single cell bioanalyzer. This equipment has been developed to measure accumulation of drugs such as doxorubicin (DOX) and fluorescently labeled paclitaxel (PTX) in single prostate cancer cells. The inhibition of drug efflux on the same prostate cell was examined in drug-sensitive and drug-resistant cells. Accumulation of these drug molecules was not found in the MDR cells, PC-3 RX-DT2R cells. Enhanced drug accumulation was observed only after treating the MDR cell in the presence of 5 μM of CsA as the MDR inhibitor. We envision this monitoring of the accumulation of fluorescent molecules (drug or fluorescent molecules), if conducted on single patient cancer cells, can provide information for clinical monitoring of patients undergoing chemotherapy in the future.

Vote as you go : Blending interfaces for community engagement into the urban space

This paper presents a series of studies on situated interfaces for community engagement. Firstly, we identify five recurring design challenges as well as four common strategies used to overcome them. We then assess the effectiveness of these strategies through field studies with public polling interfaces. We developed two very different polling interfaces in the form of (1) a web application running on an iPad mounted on a stand, allowing one vote at a time, and (2) a playful full-body interaction application for a large urban screen allowing concurrent participation. We deployed both interfaces in an urban precinct with high pedestrian traffic and equipped with a large urban screen. Analysing discoverability and learnability of each scenario, we derive insights regarding effective ways of blending community engagement interfaces into the built environment, while attracting the attention of passers-by and communicating the results of civic participation.

Proceedings of the Digital Cities 9 Workshop - Hackable Cities – From Subversive City Making to Systemic Change (Workshop) [Edited Proceedings]

The DC9 workshop takes place on June 27, 2015 in Limerick, Ireland and is titled “Hackable Cities: From Subversive City Making to Systemic Change”. The notion of “hacking” originates from the world of media technologies but is increasingly often being used for creative ideals and practices of city making. “City hacking” evokes more participatory, inclusive, decentralized, playful and subversive alternatives to often top-down ICT implementations in smart city making. However, these discourses about “hacking the city” are used ambiguously and are loaded with various ideological presumptions, which makes the term also problematic. For some “urban hacking” is about empowering citizens to organize around communal issues and perform aesthetic urban interventions. For others it raises questions about governance: what kind of “city hacks” should be encouraged or not, and who decides? Can city hacking be curated? For yet others, trendy participatory buzzwords like these are masquerades for deeply libertarian neoliberal values. Furthermore, a question is how “city hacking” may mature from the tactical level of smart and often playful interventions to the strategic level of enduring impact. The Digital Cities 9 workshop welcomes papers that explore the idea of “hackable city making” in constructive and critical ways.

Being here: Designing for distributed hands-on collaboration in blended interaction spaces

This paper describes a concept for supporting distributed hands-on collaboration through interaction design for the physical and the digital workspace. The Blended Interaction Spaces concept creates distributed work environments in which collaborating parties all feel that they are present “here” rather than “there”. We describe thinking and inspirations behind the Blended Interaction Spaces concept, and summarize findings from fieldwork activities informing our design. We then exemplify the Blended Interaction Spaces concept through a prototype implementation of one of four concepts.

Parallel streaming signature EM-tree: A clustering algorithm for web scale applications

The proliferation of the web presents an unsolved problem of automatically analyzing billions of pages of natural language. We introduce a scalable algorithm that clusters hundreds of millions of web pages into hundreds of thousands of clusters. It does this on a single mid-range machine using efficient algorithms and compressed document representations. It is applied to two web-scale crawls covering tens of terabytes. ClueWeb09 and ClueWeb12 contain 500 and 733 million web pages and were clustered into 500,000 to 700,000 clusters. To the best of our knowledge, such fine grained clustering has not been previously demonstrated. Previous approaches clustered a sample that limits the maximum number of discoverable clusters. The proposed EM-tree algorithm uses the entire collection in clustering and produces several orders of magnitude more clusters than the existing algorithms. Fine grained clustering is necessary for meaningful clustering in massive collections where the number of distinct topics grows linearly with collection size. These fine-grained clusters show an improved cluster quality when assessed with two novel evaluations using ad hoc search relevance judgments and spam classifications for external validation. These evaluations solve the problem of assessing the quality of clusters where categorical labeling is unavailable and unfeasible.

A review on prognostic techniques for non-stationary and non-linear rotating systems

The field of prognostics has attracted significant interest from the research community in recent times. Prognostics enables the prediction of failures in machines resulting in benefits to plant operators such as shorter downtimes, higher operation reliability, reduced operations and maintenance cost, and more effective maintenance and logistics planning. Prognostic systems have been successfully deployed for the monitoring of relatively simple rotating machines. However, machines and associated systems today are increasingly complex. As such, there is an urgent need to develop prognostic techniques for such complex systems operating in the real world. This review paper focuses on prognostic techniques that can be applied to rotating machinery operating under non-linear and non-stationary conditions. The general concept of these techniques, the pros and cons of applying these methods, as well as their applications in the research field are discussed. Finally, the opportunities and challenges in implementing prognostic systems and developing effective techniques for monitoring machines operating under non-stationary and non-linear conditions are also discussed.

Near infrared spectroscopy of selected natural magnesium carbonates: implications for geosequestration

The approach to remove greenhouse gases by pumping liquid CO2 several kilometres below the ground implies that many carbonate containing minerals will be formed. Among these minerals, the formation of hydromagnesite, dypingite and nesquehonite are possible, thus necessitating a study of such minerals. These minerals with a hydrotalcite-related formulae have been characterised by a combination of infrared and near infrared spectroscopy. Layered double hydroxides (also known as anionic clays or hydrotalcites) are a group of layered clay minerals described by the general formula: [M1–x2+Mx3+(OH)2]x+[An–]x/n∙mH2O. The infrared spectra of the minerals are characterised by OH and water stretching vibrations. Both the first and second fundamental overtones of these bands are observed in the NIR spectra in the 7030–7235 cm–1 and 10,490–10,570 cm–1 spectral ranges. Intense (CO3)2– symmetrical and anti-symmetrical stretching vibrations confirm the distortion of the carbonate anion. The position of the water bending vibration indicates water is strongly hydrogen-bonded to the carbonate anion in the mineral structure. NIR spectroscopy offers a method for quickly analysing such materials.

Identification of a BRCA1-mRNA splicing complex required for efficient DNA repair and maintenance of genomic stability

Mutations within BRCA1 predispose carriers to a high risk of breast and ovarian cancers. BRCA1 functions to maintain genomic stability through the assembly of multiple protein complexes involved in DNA repair, cell-cycle arrest, and transcriptional regulation. Here, we report the identification of a DNA damage-induced BRCA1 protein complex containing BCLAF1 and other key components of the mRNA-splicing machinery. In response to DNA damage, this complex regulates pre-mRNA splicing of a number of genes involved in DNA damage signaling and repair, thereby promoting the stability of these transcripts/proteins. Further, we show that abrogation of this complex results in sensitivity to DNA damage, defective DNA repair, and genomic instability. Interestingly, mutations in a number of proteins found within this complex have been identified in numerous cancer types. These data suggest that regulation of splicing by the BRCA1-mRNA splicing complex plays an important role in the cellular response to DNA damage.

Zombies on the road: A holistic design approach to balancing gamification and safe driving

This paper explores novel driving experiences that make use of gamification and augmented reality in the car. We discuss our design considerations, which are grounded in road safety psychology and video game design theory. We aim to address the tension between safe driving practices and player engagement. Specifically, we propose a holistic, iterative thinking process inspired by game design cognition and share our insights generated through the application of this process. We present preliminary game concepts that blend digital components with physical elements from the driving environment. We further highlight how this design process helped us to iteratively evolve these concepts towards being safer while maintaining fun. These insights and game design cognition itself will be useful to the AutomotiveUI community investigating similar novel driving experiences.

Robust Web content extraction

We present an empirical evaluation and comparison of two content extraction methods in HTML: absolute XPath expressions and relative XPath expressions. We argue that the relative XPath expressions, although not widely used, should be used in preference to absolute XPath expressions in extracting content from human-created Web documents. Evaluation of robustness covers four thousand queries executed on several hundred webpages. We show that in referencing parts of real world dynamic HTML documents, relative XPath expressions are on average significantly more robust than absolute XPath ones.

Acoustic adaptation in cross database audio visual SHMM training for phonetic spoken term detection

Visual information in the form of lip movements of the speaker has been shown to improve the performance of speech recognition and search applications. In our previous work, we proposed cross database training of synchronous hidden Markov models (SHMMs) to make use of external large and publicly available audio databases in addition to the relatively small given audio visual database. In this work, the cross database training approach is improved by performing an additional audio adaptation step, which enables audio visual SHMMs to benefit from audio observations of the external audio models before adding visual modality to them. The proposed approach outperforms the baseline cross database training approach in clean and noisy environments in terms of phone recognition accuracy as well as spoken term detection (STD) accuracy.

Mutations in the gene encoding IFT dynein complex component WDR34 cause jeune asphyxiating thoracic dystrophy

Bidirectional (anterograde and retrograde) motor-based intraflagellar transport (IFT) governs cargo transport and delivery processes that are essential for primary cilia growth and maintenance and for hedgehog signaling functions. The IFT dynein-2 motor complex that regulates ciliary retrograde protein transport contains a heavy chain dynein ATPase/motor subunit, DYNC2H1, along with other less well functionally defined subunits. Deficiency of IFT proteins, including DYNC2H1, underlies a spectrum of skeletal ciliopathies. Here, by using exome sequencing and a targeted next-generation sequencing panel, we identified a total of 11 mutations in WDR34 in 9 families with the clinical diagnosis of Jeune syndrome (asphyxiating thoracic dystrophy). WDR34 encodes a WD40 repeat-containing protein orthologous to Chlamydomonas FAP133, a dynein intermediate chain associated with the retrograde intraflagellar transport motor. Three-dimensional protein modeling suggests that the identified mutations all affect residues critical for WDR34 protein-protein interactions. We find that WDR34 concentrates around the centrioles and basal bodies in mammalian cells, also showing axonemal staining. WDR34 coimmunoprecipitates with the dynein-1 light chain DYNLL1 in vitro, and mining of proteomics data suggests that WDR34 could represent a previously unrecognized link between the cytoplasmic dynein-1 and IFT dynein-2 motors. Together, these data show that WDR34 is critical for ciliary functions essential to normal development and survival, most probably as a previously unrecognized component of the mammalian dynein-IFT machinery.

Delay tolerant routing protocols for energy-neutral animal tracking

This paper investigates communication protocols for relaying sensor data from animal tracking applications back to base stations. While Delay Tolerant Networks (DTNs) are well suited to such challenging environments, most existing protocols do not consider the available energy that is particularly important when tracking devices can harvest energy. This limits both the network lifetime and delivery probability in energy-constrained applications to the point when routing performance becomes worse than using no routing at all. Our work shows that substantial improvement in data yields can be achieved through simple yet efficient energy-aware strategies. Conceptually, there is need for balancing the energy spent on sensing, data mulling, and delivery of direct packets to destination. We use empirical traces collected in a flying fox (fruit bat) tracking project and show that simple threshold-based energy-aware strategies yield up to 20% higher delivery rates. Furthermore, these results generalize well for a wide range of operating conditions.

Flow evaluation and hemolysis analysis of BVAD centrifugal blood pump by computational fluids dynamics

Computational fluid dynamics (CFD) and particle image velocimetry (PIV) are commonly used techniques to evaluate the flow characteristics in the development stage of blood pumps. CFD technique allows rapid change to pump parameters to optimize the pump performance without having to construct a costly prototype model. These techniques are used in the construction of a bi-ventricular assist device (BVAD) which combines the functions of LVAD and RVAD in a compact unit. The BVAD construction consists of two separate chambers with similar impellers, volutes, inlet and output sections. To achieve the required flow characteristics of an average flow rate of 5 l/min and different pressure heads (left – 100mmHg and right – 20mmHg), the impellers were set at different rotating speeds. From the CFD results, a six-blade impeller design was adopted for the development of the BVAD. It was also observed that the fluid can flow smoothly through the pump with minimum shear stress and area of stagnation which are related to haemolysis and thrombosis. Based on the compatible Reynolds number the flow through the model was calculated for the left and the right pumps. As it was not possible to have both the left and right chambers in the experimental model, the left and right pumps were tested separately.

Document timespan normalisation and understanding temporality for clinical records search

Previous qualitative research has highlighted that temporality plays an important role in relevance for clinical records search. In this study, an investigation is undertaken to determine the effect that the timespan of events within a patient record has on relevance in a retrieval scenario. In addition, based on the standard practise of document length normalisation, a document timespan normalisation model that specifically accounts for timespans is proposed. Initial analysis revealed that in general relevant patient records tended to cover a longer timespan of events than non-relevant patient records. However, an empirical evaluation using the TREC Medical Records track supports the opposite view that shorter documents (in terms of timespan) are better for retrieval. These findings highlight that the role of temporality in relevance is complex and how to effectively deal with temporality within a retrieval scenario remains an open question.