Tackling resistance: Emerging antimalarials and new parasite targets in the era of elimination [version 1; referees: 2 approved]

Malaria remains a significant contributor to global human mortality, and roughly half the world’s population is at risk for infection with Plasmodium spp. parasites. Aggressive control measures have reduced the global prevalence of malaria significantly over the past decade. However, resistance to available antimalarials continues to spread, including resistance to the widely used artemisinin-based combination therapies. Novel antimalarial compounds and therapeutic targets are greatly needed. This review will briefly discuss several promising current antimalarial development projects, including artefenomel, ferroquine, cipargamin, SJ733, KAF156, MMV048, and tafenoquine. In addition, we describe recent large-scale genetic and resistance screens that have been instrumental in target discovery. Finally, we highlight new antimalarial targets, which include essential transporters and proteases. These emerging antimalarial compounds and therapeutic targets have the potential to overcome multi-drug resistance in ongoing efforts toward malaria elimination

A study of the Boston Naval Shipyard's community relations problems

Thesis (M.S.)--Boston Universit

Polymer matrix and graphite fiber interface study

Hercules AS4 graphite fiber, unsized, or with EPON 828, PVA, or polysulfone sizing, was combined with three different polymer matrices. These included Hercules 3501-6 epoxy, Hercules 4001 bismaleimide, and Hexcel F155 rubber toughened epoxy. Unidirectional composites in all twelve combinations were fabricated and tested in transverse tension and axial compression. Quasi-isotropic laminates were tested in axial tension and compression, flexure, interlaminar shear, and tensile impact. All tests were conducted at both room temperature, dry and elevated temperature, and wet conditions. Single fiber pullout testing was also performed. Extensive scanning electron microphotographs of fracture surfaces are included, along with photographs of single fiber pullout failures. Analytical/experimental correlations are presented, based on the results of a finite element micromechanics analysis. Correlations between matrix type, fiber sizing, hygrothermal environment, and loading mode are presented. Results indicate that the various composite properties were only moderately influenced by the fiber sizings utilized

Stability and evolution of transcriptional regulatory networks

How do transcriptional regulatory networks elicit stable gene expression patterns? How do such networks evolve? These topics have kept molecular biologists occupied for years. The recent elucidation of regulatory networks that control endoderm development, including ‘genomic location analysis ’ of transcription factors in endoderm-derived liver cells, provides more comprehensive views than in the past. But how much more have we learned? Genome location analysis, or ChIP-on-chip, first involves crosslinking chromatin in native cells, breaking it into small fragments (e.g., 0.5–1 kb), immunoprecipitating the fragments that contain a specific transcription factor antigen (ChIP), and performing ligation-mediated PCR to amplify the ChIP fragments. The amplified DNA pool is then labeled and hybridized to a microarray (chip) containing single-stranded DNA probe

Optical Pumping of TeH+: Implications for the Search for Varying mp/me

Molecular overtone transitions provide optical frequency transitions sensitive to variation in the proton-to-electron mass ratio ($\mu\equiv m_p/m_e$). However, robust molecular state preparation presents a challenge critical for achieving high precision. Here, we characterize infrared and optical-frequency broadband laser cooling schemes for TeH$^+$, a species with multiple electronic transitions amenable to sustained laser control. Using rate equations to simulate laser cooling population dynamics, we estimate the fractional sensitivity to $\mu$ attainable using TeH$^+$. We find that laser cooling of TeH$^+$ can lead to significant improvements on current $\mu$ variation limits

One-electron states and interband optical absorption in single-wall carbon nanotubes

Explicit expressions for the wave functions and dispersion equation for the band p - electrons in single-wall carbon nanotubes are obtained within the method of zero-range potentials. They are then used to investigate the absorption spectrum of polarized light caused by direct interband transitions in isolated nanotubes. It is shown that, at least, under the above approximations, the circular dichroism is absent in chiral nanotubes for the light wave propagating along the tube axis. The results obtained are compared with those calculated in a similar way for a graphite plane.Comment: 16 pages, 8 figures, 1 tabl