Ertapenem-Induced Encephalopathy in a Patient With Normal Renal Function

Drug-induced neurotoxicity is a rare adverse reaction associated with ertapenem. Encephalopathy is a type of neurotoxicity that is defined as a diffuse disease of the brain that alters brain function or structure. We report a patient with normal renal function who developed ertapenem-induced encephalopathy manifesting as altered mental status, hallucinations, and dystonic symptoms. The patient’s symptoms improved dramatically following ertapenem discontinuation, consistent with case reports describing ertapenem neurotoxicity in renal dysfunction. Since clinical evidence strongly suggested ertapenem causality, we utilized the Naranjo Scale to estimate the probability of an adverse drug reaction to ertapenem. Our patient received a Naranjo Scale score of 7, suggesting a probable adverse drug reaction, with a reasonable temporal sequence to support our conclusion

A target repurposing approach identifies N-myristoyltransferase as a new candidate drug target in filarial nematodes

Myristoylation is a lipid modification involving the addition of a 14-carbon unsaturated fatty acid, myristic acid, to the N-terminal glycine of a subset of proteins, a modification that promotes their binding to cell membranes for varied biological functions. The process is catalyzed by myristoyl-CoA:protein N-myristoyltransferase (NMT), an enzyme which has been validated as a drug target in human cancers, and for infectious diseases caused by fungi, viruses and protozoan parasites. We purified Caenorhabditis elegans and Brugia malayi NMTs as active recombinant proteins and carried out kinetic analyses with their essential fatty acid donor, myristoyl-CoA and peptide substrates. Biochemical and structural analyses both revealed that the nematode enzymes are canonical NMTs, sharing a high degree of conservation with protozoan NMT enzymes. Inhibitory compounds that target NMT in protozoan species inhibited the nematode NMTs with IC50 values of 2.5-10 nM, and were active against B. malayi microfilariae and adult worms at 12.5 µM and 50 µM respectively, and C. elegans (25 µM) in culture. RNA interference and gene deletion in C. elegans further showed that NMT is essential for nematode viability. The effects observed are likely due to disruption of the function of several downstream target proteins. Potential substrates of NMT in B. malayi are predicted using bioinformatic analysis. Our genetic and chemical studies highlight the importance of myristoylation in the synthesis of functional proteins in nematodes and have shown for the first time that NMT is required for viability in parasitic nematodes. These results suggest that targeting NMT could be a valid approach for the development of chemotherapeutic agents against nematode diseases including filariasis

The Gravitational Wave Treasure Map: A Tool to Coordinate, Visualize, and Assess the Electromagnetic Follow-Up of Gravitational Wave Events

We present the Gravitational Wave Treasure Map, a tool to coordinate, visualize, and assess the electromagnetic follow-up of gravitational wave (GW) events. With typical GW localization regions of hundreds to thousands of square degrees and dozens of active follow-up groups, the pursuit of electromagnetic (EM) counterparts is a challenging endeavor, but the scientific payoff for early discovery of any counterpart is clear. With this tool, we provide a website and API interface that allows users to easily see where other groups have searched and better inform their own follow-up search efforts. A strong community of Treasure Map users will increase the overall efficiency of EM counterpart searches and will play a fundamental role in the future of multi-messenger astronomy.Comment: 14 pages, 8 figures, Accepted to Ap

An open-source platform for pediatric cancer data exploration: a report from Data for the Common Good

Objective: The Pediatric Cancer Data Commons (PCDC)-a project of Data for the Common Good-houses clinical pediatric oncology data and utilizes the open-source Gen3 platform. To meet the needs of end users, the PCDC development team expanded the out-of-box functionality and developed additional custom features that should be useful to any group developing similar data commons. Materials and methods: Modifications of the PCDC data portal software were implemented to facilitate desired functionality. Results: Newly developed functionality includes updates to authorization methods, expansion of filtering capabilities, and addition of data analysis functions. Discussion: We describe the process by which custom functionalities were developed. Features are open source and available to be implemented and adapted to suit needs of data portals that utilize the Gen3 platform. Conclusion: Data portals are indispensable tools for facilitating data sharing. Open-source infrastructure facilitates a modular and collaborative approach for meeting needs of end users and stakeholders.</p

Hectospec, the MMT's 300 Optical Fiber-Fed Spectrograph

The Hectospec is a 300 optical fiber fed spectrograph commissioned at the MMT in the spring of 2004. A pair of high-speed six-axis robots move the 300 fiber buttons between observing configurations within ~300 s and to an accuracy ~25 microns. The optical fibers run for 26 m between the MMT's focal surface and the bench spectrograph operating at R~1000-2000. Another high dispersion bench spectrograph offering R~5,000, Hectochelle, is also available. The system throughput, including all losses in the telescope optics, fibers, and spectrograph peaks at ~10% at the grating blaze in 1" FWHM seeing. Correcting for aperture losses at the 1.5" diameter fiber entrance aperture, the system throughput peaks at $\sim$17%. Hectospec has proven to be a workhorse instrument at the MMT. Hectospec and Hectochelle together were scheduled for 1/3 of the available nights since its commissioning. Hectospec has returned \~60,000 reduced spectra for 16 scientific programs during its first year of operation.Comment: 68 pages, 28 figures, to appear in December 2005 PAS

Quantum dots with even number of electrons: Kondo effect in a finite magnetic field

We study a small spin-degenerate quantum dot with even number of electrons, weakly connected by point contacts to the metallic electrodes, and subject to an external magnetic field. If the Zeeman energy B is equal to the single-particle level spacing $\Delta$ in the dot, the ground state of the dot becomes doubly degenerate, and the system exhibits Kondo effect, despite the fact that B exceeds by far the Kondo temperature $T_{K}$. A possible realization of this in tunneling experiments is discussed

Orion Capsule Handling Qualities for Atmospheric Entry

Two piloted simulations were conducted at NASA's Johnson Space Center using the Cooper-Harper scale to study the handling qualities of the Orion Command Module capsule during atmospheric entry flight. The simulations were conducted using high fidelity 6-DOF simulators for Lunar Return Skip Entry and International Space Station Return Direct Entry flight using bank angle steering commands generated by either the Primary (PredGuid) or Backup (PLM) guidance algorithms. For both evaluations, manual control of bank angle began after descending through Entry Interface into the atmosphere until drogue chutes deployment. Pilots were able to use defined bank management and reversal criteria to accurately track the bank angle commands, and stay within flight performance metrics of landing accuracy, g-loads, and propellant consumption, suggesting that the pilotability of Orion under manual control is both achievable and provides adequate trajectory performance with acceptable levels of pilot effort. Another significant result of these analyses is the applicability of flying a complex entry task under high speed entry flight conditions relevant to the next generation Multi Purpose Crew Vehicle return from Mars and Near Earth Objects