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

Utopia

group exhibition of work by Canterbury Christ Church University staff and student

Effects of Lake Management on Chemical, Physical, and Phycological Characteristics of a Hypereutrophic Reservoir

Lake Charleston is a 1.1 billion gallon capacity side channel reservoir which was constructed in 1982 as a public drinking water supply for the City of Charleston in Coles County, Illinois. Past studies of the lake indicated an increase in eutrophication and the capacity to support large algal populations. Recent lake management practices include copper sulfate applications as an algicide and aeration to reduce flavor and odor. In order to assess present lake status and to evaluate the effectiveness of lake management practices, two lake sites were sampled on a weekly basis from May to October, 1989. Chemical, physical, and phycological analyses followed standard methods (APHA 1985). Carlson\u27s Trophic State Indices calculated from data on secchi depth (m), chlorophyll a (ug/L), and total phosphorus (mg/L) indicated that Lake Charleston is hypereutrophic. Phosphorus probably limited algal standing crop at site 3 while light was most likely the limiting factor at site 1. Abundance of phosphorus at site 1 was attributed to the circulation of hypolimnetic phosphorus by the aeration unit. Phytoplankton density has increased by a factor greater than five since 1982. During a bloom in July, bluegreen algae dominated at site 3, however bluegreens never comprised more than fifty percent of total algae at site 1. The inability of bluegreens to dominate at site 1 could have resulted from low pH/high carbon dioxide water circulated from the bottom which would favor dominance by green algae. After copper sulfate treatment in late July, phytoplankton density decreased dramatically and green algae resumed dominance at site 3. Several chemical, physical, and phycological parameters were significantly correlated. Site specific differences were observed and attributed to the effects of aeration. Aeration may be a good management option for Lake Charleston with higher carbon dioxide and lower pH levels at site 1 presumably preventing bluegreen algal dominance. Total algal biomass should decrease with continued and/or extended aeration as nutrient concentrations level off and algae become light limited. Copper sulfate, which is toxic to zooplankton, could then be eliminated as a management technique and increased zooplankton populations could possibly provide biological control for phytoplankton. Dissolved oxygen has not yet increased, possibly because of an increase in oxygen demanding substances and a decrease in photosynthesis, both of which are attributable to circulation. With constant aeration, dissolved oxygen should eventually increase and overall lake conditions should improve