Cofactor Genomics: A Sequencing Service Company Emerges from the Technology Development Laboratory

Jump Starting Technologies, Patent Issues, and Translational Medicine Poster SessionCofactor Genomics is based in St. Louis, MO and provides sequencing and analysis services to academic and industry clients. We are a small company committed to changing the service sequencing paradigm by offering our customers front-to-back solutions; experimental design, next-generation sequencing, and advanced analytics for their work. Cofactor Genomics was founded by individuals with one-of-a-kind experience in Next-Generation sequencing technology development. The Cofactor Genomics executive team spent a collective 35 years working in the Technology Development Group at The Genome Center at Washington University in St. Louis, Missouri. From early 2004 to late 2008, their primary responsibilities within the group were to investigate, evaluate and develop both wet-lab and computational applications for emerging Next-Generation sequencing technology platforms. Their experience began with beta testing the 454 Life Sciences (now Roche) GS 20, continued with beta testing the first serial numbered instrument from Solexa (now Illumina), and culminated with beta testing the Applied Biosystems (now Life Technologies) SOLiD instrument. Our individual experiences were unique within the realm of next-generation sequencing technology, thus extremely complimentary for a consolidation and commercialization of skill sets; Matt Hickenbotham became a renowned expert in library construction and Next-Gen instrumentation, Jon Armstrong emerged as an expert in targeted and reduced representation genomic sequencing, and Ryan Richt and Dr. Jarret Glasscock were two of the first individuals in the world to characterize the data generated by these instruments. It is this early-access wet-lab and computational experience with these disruptive sequencing technologies that provided the foundation for operations at Cofactor Genomics. Cofactor Genomics has been in operation for 2 years and has already established a proven track record of capability, versatility, remarkably consistent high quality data generation, and delivering custom data analysis solutions. We constructed 268 different sequencing libraries in our first year spanning nearly every sequencing application and multiple Next-Gen instrument platforms. This feat would be impossible for any firm other than Cofactor to complete in such a short time frame, much to the credit of our highly skilled and talented team. We pooled our talents to form a company offering customers end-to-end sequencing solutions that ultimately allow them to concentrate on what they do best, breakthrough research

On-orbit Validation of the Geolocation Accuracy of the GOES-16 Geostationary Lightning Mapper (GLM) Flashes Using Ground-based Laser Beacons

As part of the geolocation accuracy assessment of lightning flashes detected by the Geostationary Lightning Mapper (GLM) on the GOES-16 and GOES-17 satellites (Geostationary Operational Environmental Satellite), two satellite laser ranging stations employed laser beacon systems to generate transient light pulses that simulate natural lightning around 777.4 nm to validate the pre-launch spec of 5 km. The pulse width, repetition rate, wavelength, and power of the laser-pulses were configured to produce sufficient instrument response to be detected as synthetic lightning events by the GLM instrument. During the testing period from April 2017 to January 2018, the laser systems illuminated the GOES-16 satellite to observe diurnal variation of the GLM system response, with particular emphasis on geolocation accuracy. The final GOES-16 laser beacon tests, which used the latest updates of the geolocation algorithms implemented by the GOES-R Ground Segment, showed the offsets between the GLM geolocated location and the known laser locations were within 5 km

Phase I Study Assessing the Pharmacokinetic Profile, Safety, and Tolerability of a Single Dose of Ceftazidime-Avibactam in Hospitalized Pediatric Patients.

This study aimed to investigate the pharmacokinetics (PK), safety, and tolerability of a single dose of ceftazidime-avibactam in pediatric patients. A phase I, multicenter, open-label PK study was conducted in pediatric patients hospitalized with an infection and receiving systemic antibiotic therapy. Patients were enrolled into four age cohorts (cohort 1, ≥12 to <18 years; cohort 2, ≥6 to <12 years; cohort 3, ≥2 to <6 years; cohort 4, ≥3 months to <2 years). Patients received a single 2-h intravenous infusion of ceftazidime-avibactam (cohort 1, 2,000 to 500 mg; cohort 2, 2,000 to 500 mg [≥40 kg] or 50 to 12.5 mg/kg [<40 kg]; cohorts 3 and 4, 50 to 12.5 mg/kg). Blood samples were collected to describe individual PK characteristics for ceftazidime and avibactam. Population PK modeling was used to describe characteristics of ceftazidime and avibactam PK across all age groups. Safety and tolerability were assessed. Thirty-two patients received study drug. Mean plasma concentration-time curves, geometric mean maximum concentration (Cmax), and area under the concentration-time curve from time zero to infinity (AUC0-∞) were similar across all cohorts for both drugs. Six patients (18.8%) reported an adverse event, all mild or moderate in intensity. No deaths or serious adverse events occurred. The single-dose PK of ceftazidime and avibactam were comparable between each of the 4 age cohorts investigated and were broadly similar to those previously observed in adults. No new safety concerns were identified. (This study has been registered at ClinicalTrials.gov under registration no. NCT01893346.)

Admissions Scandal

The American Democracy Project kicks off the year with the first Times Talk of the semester on Thursday, September 5th at 12-1pm in the South Study Area of Forsyth Library. Jon Armstrong and Carolyn Tatro from the Office of Admissions present on the Admissions Scandal. Free pizza and salad provided to the first 20 attendees

Paediatric malaria case-management with Artemether-Lumefantrine in Zambia: a repeat cross-sectional study

BACKGROUND Zambia was the first African country to change national antimalarial treatment policy to artemisinin-based combination therapy – artemether-lumefantrine. An evaluation during the early implementation phase revealed low readiness of health facilities and health workers to deliver artemether-lumefantrine, and worryingly suboptimal treatment practices. Improvements in the case-management of uncomplicated malaria two years after the initial evaluation and three years after the change of policy in Zambia are reported. METHODS Data collected during the health facility surveys undertaken in 2004 and 2006 at all outpatient departments of government and mission facilities in four Zambian districts were analysed. The surveys were cross-sectional, using a range of quality of care assessment methods. The main outcome measures were changes in health facility and health worker readiness to deliver artemether-lumefantrine, and changes in case-management practices for children below five years of age presenting with uncomplicated malaria as defined by national guidelines. RESULTS. In 2004, 94 health facilities, 103 health workers and 944 consultations for children with uncomplicated malaria were evaluated. In 2006, 104 facilities, 135 health workers and 1125 consultations were evaluated using the same criteria of selection. Health facility and health worker readiness improved from 2004 to 2006: availability of artemether-lumefantrine from 51% (48/94) to 60% (62/104), presence of artemether-lumefantrine dosage wall charts from 20% (19/94) to 75% (78/104), possession of guidelines from 58% (60/103) to 92% (124/135), and provision of in-service training from 25% (26/103) to 41% (55/135). The proportions of children with uncomplicated malaria treated with artemether-lumefantrine also increased from 2004 to 2006: from 1% (6/527) to 27% (149/552) in children weighing 5 to 9 kg, and from 11% (42/394) to 42% (231/547) in children weighing 10 kg or more. In both weight groups and both years, 22% (441/2020) of children with uncomplicated malaria were not prescribed any antimalarial drug. CONCLUSION Although significant improvements in malaria case-management have occurred over two years in Zambia, the quality of treatment provided at the point of care is not yet optimal. Strengthening weak health systems and improving the delivery of effective interventions should remain high priority in all countries implementing new treatment policies for malaria.Zambian-Boston University Malaria Project; Health Systems & Services Project sub-contract to Boston University/CIHD by means of a cooperative agreement with USAID/Zambia (Contract number 690-C-00-04-00153-00); Wellcome Trust U

Mapping our Universe in 3D with MITEoR

Mapping our universe in 3D by imaging the redshifted 21 cm line from neutral hydrogen has the potential to overtake the cosmic microwave background as our most powerful cosmological probe, because it can map a much larger volume of our Universe, shedding new light on the epoch of reionization, inflation, dark matter, dark energy, and neutrino masses. We report on MITEoR, a pathfinder low-frequency radio interferometer whose goal is to test technologies that greatly reduce the cost of such 3D mapping for a given sensitivity. MITEoR accomplishes this by using massive baseline redundancy both to enable automated precision calibration and to cut the correlator cost scaling from N^2 to NlogN, where N is the number of antennas. The success of MITEoR with its 64 dual-polarization elements bodes well for the more ambitious HERA project, which would incorporate many identical or similar technologies using an order of magnitude more antennas, each with dramatically larger collecting area.Comment: To be published in proceedings of 2013 IEEE International Symposium on Phased Array Systems & Technolog

Separation of rare gases and chiral molecules by selective binding in porous organic cages

The separation of molecules with similar size and shape is an important technological challenge. For example, rare gases can pose either an economic opportunity or an environmental hazard and there is a need to separate these spherical molecules selectively at low concentrations in air. Likewise, chiral molecules are important building blocks for pharmaceuticals, but chiral enantiomers, by definition, have identical size and shape, and their separation can be challenging. Here we show that a porous organic cage molecule has unprecedented performance in the solid state for the separation of rare gases, such as krypton and xenon. The selectivity arises from a precise size match between the rare gas and the organic cage cavity, as predicted by molecular simulations. Breakthrough experiments demonstrate real practical potential for the separation of krypton, xenon and radon from air at concentrations of only a few parts per million. We also demonstrate selective binding of chiral organic molecules such as 1-phenylethanol, suggesting applications in enantioselective separation

Separation of rare gases and chiral molecules by selective binding in porous organic cages

The separation of molecules with similar size and shape is an important technological challenge. For example, rare gases can pose either an economic opportunity or an environmental hazard and there is a need to separate these spherical molecules selectively at low concentrations in air. Likewise, chiral molecules are important building blocks for pharmaceuticals, but chiral enantiomers, by definition, have identical size and shape, and their separation can be challenging. Here we show that a porous organic cage molecule has unprecedented performance in the solid state for the separation of rare gases, such as krypton and xenon. The selectivity arises from a precise size match between the rare gas and the organic cage cavity, as predicted by molecular simulations. Breakthrough experiments demonstrate real practical potential for the separation of krypton, xenon and radon from air at concentrations of only a few parts per million. We also demonstrate selective binding of chiral organic molecules such as 1-phenylethanol, suggesting applications in enantioselective separation