Optical nanolithography using a scanning near-field probe with an integrated light source

An ultracompact near-field optical probe is described that is based on a single, integrated assembly consisting of a gallium nitride (GaN) light-emitting diode (LED), a microlens, and a cantilever assembly containing a hollow pyramidal probe with a subwavelength aperture at its apex. The LED emits ultraviolet light and may be used as a light source for near-field photolithographic exposure. Using this simple device compatible with many commercial atomic force microscope systems, it is possible to form nanostructures in photoresist with a resolution of 35 nm, corresponding to λ/10. © 2008 American Institute of Physics

Climate adaptation by crop migration.

Many studies have estimated the adverse effects of climate change on crop yields, however, this literature almost universally assumes a constant geographic distribution of crops in the future. Movement of growing areas to limit exposure to adverse climate conditions has been discussed as a theoretical adaptive response but has not previously been quantified or demonstrated at a global scale. Here, we assess how changes in rainfed crop area have already mediated growing season temperature trends for rainfed maize, wheat, rice, and soybean using spatially-explicit climate and crop area data from 1973 to 2012. Our results suggest that the most damaging impacts of warming on rainfed maize, wheat, and rice have been substantially moderated by the migration of these crops over time and the expansion of irrigation. However, continued migration may incur substantial environmental costs and will depend on socio-economic and political factors in addition to land suitability and climate

Intermittency, fluctuations and maximal chaos in an emergent universal state of active turbulence

A hydrodynamic model of active, low Reynolds number suspensions, shows the emergence of an asymptotic state with a universal spectral scaling and non-Gaussian (intermittent) fluctuations in the velocity field. Such states arise when these systems are pushed beyond a critical level of activity and show features akin to high Reynolds number, inertial turbulence. We provide compelling numerical and analytical evidence for the existence of such a transition at a critical value of activity and further show that the maximally chaotic states are tied to this transition.Comment: 8 Pages, 4 Figure

Otterbein Miscellany , May 1970

https://digitalcommons.otterbein.edu/miscellany/1018/thumbnail.jp

The Otterbein Miscellany - May 1971

https://digitalcommons.otterbein.edu/miscellany/1000/thumbnail.jp

Kinase domain mutations confer resistance to novel inhibitors targeting JAK2V617F in myeloproliferative neoplasms

The transforming JAK2V617F kinase is frequently associated with myeloproliferative neoplasms (MPNs) and thought to be instrumental for the overproduction of myeloid lineage cells. Several small molecule drugs targeting JAK2 are currently in clinical development for treatment in these diseases. We performed a high-throughput in vitro screen to identify point mutations in JAK2V617F that would be predicted to have potential clinical relevance and associated with drug resistance to the JAK2 inhibitor ruxolitinib (INCB018424). Seven libraries of mutagenized JAK2V617F cDNA were screened to specifically identify mutations in the predicted drug-binding region that would confer resistance to ruxolitinib, using a BaF3 cell-based assay. We identified 5 different non-synonymous point mutations that conferred drug resistance. Cells containing mutations had a 9 to 33-fold higher EC50 for ruxolitinib compared to native JAK2V617F. Our results further indicated that these mutations also conferred cross-resistance to all JAK2 kinase inhibitors tested, including AZD1480, TG101348, lestaurtinib (CEP-701) and CYT-387. Surprisingly, introduction of the ‘gatekeeper’ mutation (M929I) in JAK2V617F affected only ruxolitinib sensitivity (4-fold increase in EC50). These results suggest that JAK2 inhibitors currently in clinical trials may be prone to resistance as a result of point mutations and caution should be exercised when administering these drugs

Skill tests of three-dimensional tidal currents in a global ocean model: A look at the North Atlantic

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/92458/1/jgr_timkoetal_northatlatnictidalcurrentskilltest_2012.pd

The Otterbein Miscellany - October 1975

https://digitalcommons.otterbein.edu/miscellany/1015/thumbnail.jp

Antitumor activity and safety of the PARP inhibitor rucaparib in patients with high grade ovarian carcinoma and a germline or somatic BRCA1 or BRCA2 mutation: integrated analysis of data from Study 10 and ARIEL2

Objective: An integrated analysis was undertaken to characterize the antitumor activity and safety profile of the oral poly(ADP-ribose) polymerase inhibitor rucaparib in patients with relapsed high-grade ovarian carcinoma (HGOC). Methods: Eligible patients from Study 10 (NCT01482715) and ARIEL2 (NCT01891344) who received a starting dose of oral rucaparib 600 mg twice daily (BID) with or without food were included in these analyses. The integrated efficacy population included patients with HGOC and a deleterious germline or somatic BRCA1 or BRCA2 (BRCA1/2) mutation who received at least two prior chemotherapies and were sensitive, resistant, or refractory to platinum-based chemotherapy. The primary endpoint was investigator-assessed confirmed objective response rate (ORR). Secondary endpoints included duration of response (DOR) and progression-free survival (PFS). The integrated safety population included patients with HGOC who received at least one dose of rucaparib 600 mg BID, irrespective of BRCA1/2 mutation status and prior treatments. Results: In the efficacy population (n = 106), ORR was 53.8% (95% confidence interval [CI], 43.8–63.5); 8.5% and 45.3% of patients achieved complete and partial responses, respectively. Median DOR was 9.2 months (95% CI, 6.6–11.6). In the safety population (n = 377), the most frequent treatment-emergent adverse events (AEs) were nausea, asthenia/fatigue, vomiting, and anemia/hemoglobin decreased. The most common grade ≥ 3 treatment-emergent AE was anemia/hemoglobin decreased. Treatment-emergent AEs led to treatment interruption, dose reduction, and treatment discontinuation in 58.6%, 45.9%, and 9.8% of patients, respectively. No treatment-related deaths occurred. Conclusions: Rucaparib has antitumor activity in advanced BRCA1/2-mutated HGOC and a manageable safety profile