Preclinical Evaluation of Ureidosulfamate Carbonic Anhydrase IX/XII Inhibitors in the Treatment of Cancers

Carbonic anhydrases (CAs) are a family of enzymes involved in the pH regulation of metabolically active cells/tissues. Upregulation of the CAIX/XII isoforms is associated with hypoxic tumours and clinically linked with malignant progression, treatment resistance and poor prognosis. The elucidation of the crystal structure of the catalytic domains of CAIX/XII provided the basis for the generation of CAIX/XII selective inhibitors based on the sulfonamide, sulfamate and coumarins chemical structures. Ureido-substituted benzenesulfonamide CAIX/XII inhibitors have shown significant potential, with U-104 (SLC-0111) currently present in clinical Phase I/II. Ureido-substituted sulfamate CAIX/XII inhibitors have received less attention despite encouraging preclinical test results. In triple-negative breast cancer (TNBC), ureidosulfamates revealed a significant antitumour (FC9-398A) and antimetastatic potential (S4). In small cell lung cancer (SCLC), a cancer cell type very sensitive to a dysregulation in CAIX signaling, S4 treatment was particularly effective when combined with cisplatin with no evidence of acquired cisplatin-resistance. These successful anticancer strategies should provide a solid basis for future studies on ureido-substituted sulfamates

Science vs. science: the complexities of interdisciplinary research

Human-Computer Interaction and Web Science are radically interdisciplinary fields, but what does this mean in practical terms? Undertaking research (and writing papers) that encompass multiple disciplinary perspectives and methods is a serious challenge and it is difficult to maintain conferences that fairly review and host contributions from multiple disciplines. The colocation of the ACM WebSci conference with CHI in Paris, offers an unusual opportunity to bring these two communities together. Previous discussions have considered how to conduct interdisciplinary work that bridges HCI/WebSci with specific areas. Our objective is to provide a space for interested researchers from both communities to share their views and approaches to tackling the tensions and complexities associated with interdisciplinary work, whatever fields are being bridged

Space processes for extended low-G testing

Results of an investigation of verifying the capabilities of space processes in ground based experiments at low-g periods are presented. Limited time experiments were conducted with the processes. A valid representation of the complete process cycle was achieved at low-g periods ranging from 40 to 390 seconds. A minimum equipment inventory, is defined. A modular equipment design, adopted to assure low cost and high program flexibility, is presented as well as procedures and data established for the synthesis and definition of dedicated and mixed rocket payloads

Measuring and modeling polymer gradients argues that spindle microtubules regulate their own nucleation

Spindles are self-organized microtubule-based structures that segregate chromosomes during cell division. The mass of the spindle is controlled by the balance between microtubule turnover and nucleation. The mechanisms that control the spatial regulation of microtubule nucleation remain poorly understood. Previous work has found that microtubule nucleators bind to microtubules in the spindle, but it is unclear if this binding regulates the activity of those nucleators. Here we use a combination of experiments and mathematical modeling to investigate this issue. We measure the concentration of tubulin and microtubules in and around the spindle. We found a very sharp decay in microtubules at the spindle interface, which is inconsistent with the activity of microtubule nucleators being independent of their association with microtubules and consistent with a model in which microtubule nucleators are only active when bound to a microtubule. This strongly argues that the activity of microtubule nucleators is greatly enhanced when bound to microtubules. Thus, microtubule nucleators are both localized and activated by the microtubules they generate

Optimal Cloning and Singlet Monogamy

The inability to produce two perfect copies of an unknown state is inherently linked with the inability to produce maximal entanglement between multiple spins. Despite this, there is no quantitative link between how much entanglement can be generated between spins (known as monogamy), and how well an unknown state can be cloned. This situation is remedied by giving a set of sufficient conditions such that the optimal Completely Positive map can be implemented as a teleportation operation into a standard, reference, state. The case of arbitrary 1 to N asymmetric cloning of d-dimensional spins can then be solved exactly, yielding the concept of `singlet monogamy'. The utility of this relation is demonstrated by calculating properties of Heisenberg systems, and contrasting them with the results from standard monogamy arguments.Comment: 4 pages, 1 figure. v2: conjecture upgraded to proof and generalized to arbitrary local hilbert space dimensions. v3: published versio

#CHIMoney: Financial interactions, digital cash, capital exchange and mobile money

Interactions around money and financial services are a critical part of our lives on and off-line. New technologies and new ways of interacting with these technologies are of huge interest; they enable new business models and ways of making sense of this most important aspect of our everyday lives. At the same time, money is an essential element in HCI research and design. This workshop is intended to bring together researchers and practitioners involved in the design and use of systems that combine digital and new media with monetary and financial interactions to build on an understanding of these technologies and their impacts on users' behaviors. The workshop will focus on social, technical, and economic aspects around everyday user interactions with money and emerging financial technologies and systems