Lithographic measurement of EUV flare in the 0.3-NA Micro ExposureTool optic at the Advanced Light Source

The level of flare present in a 0.3-NA EUV optic (the MET optic) at the Advanced Light Source at Lawrence Berkeley National Laboratory is measured using a lithographic method. Photoresist behavior at high exposure doses makes analysis difficult. Flare measurement analysis under scanning electron microscopy (SEM) and optical microscopy is compared, and optical microscopy is found to be a more reliable technique. In addition, the measured results are compared with predictions based on surface roughness measurement of the MET optical elements. When the fields in the exposure matrix are spaced far enough apart to avoid influence from surrounding fields and the data is corrected for imperfect mask contrast and aerial image proximity effects, the results match predicted values quite well. The amount of flare present in this optic ranges from 4.7% for 2 {micro}m features to 6.8% for 500 nm features

Effect of Preinjury Oral Anticoagulants on Outcomes Following Traumatic Brain Injury from Falls in Older Adults

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/156128/2/phar2435_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/156128/1/phar2435.pd

Cre-dependent DNA recombination activates a STING-dependent innate immune response

Gene-recombinase technologies, such as Cre/loxP-mediated DNA recombination, are important tools in the study of gene function, but have potential side effects due to damaging activity on DNA. Here we show that DNA recombination by Cre instigates a robust antiviral response in mammalian cells, independent of legitimate loxP recombination. This is due to the recruitment of the cytosolic DNA sensor STING, concurrent with Cre-dependent DNA damage and the accumulation of cytoplasmic DNA. Importantly, we establish a direct interplay between this antiviral response and cell-cell interactions, indicating that low cell densities in vitro could be useful to help mitigate these effects of Cre. Taking into account the wide range of interferon stimulated genes that may be induced by the STING pathway, these results have broad implications in fields such as immunology, cancer biology, metabolism and stem cell research. Further, this study sets a precedent in the field of gene-engineering, possibly applicable to other enzymatic-based genome editing technologies

Cre-dependent DNA recombination activates a STING-dependent innate immune response

Gene-recombinase technologies, such as Cre/loxP-mediated DNA recombination, are important tools in the study of gene function, but have potential side effects due to damaging activity on DNA. Here we show that DNA recombination by Cre instigates a robust antiviral response in mammalian cells, independent of legitimate loxP recombination. This is due to the recruitment of the cytosolic DNA sensor STING, concurrent with Cre-dependent DNA damage and the accumulation of cytoplasmic DNA. Importantly, we establish a direct interplay between this antiviral response and cell-cell interactions, indicating that low cell densities in vitro could be useful to help mitigate these effects of Cre. Taking into account the wide range of interferon stimulated genes that may be induced by the STING pathway, these results have broad implications in fields such as immunology, cancer biology, metabolism and stem cell research. Further, this study sets a precedent in the field of gene-engineering, possibly applicable to other enzymatic-based genome editing technologies

Characterization of the synchrotron-based 0.3-NA EUV microexposuretool at the ALS

Synchrotron-based EUV exposure tools continue to play a crucial roll in the development of EUV lithography. Utilizing a programmable-pupil-fill illuminator, the 0.3-NA microexposure tool at Lawrence Berkeley National Laboratory's Advanced Light Source synchrotron radiation facility provides the highest resolution EUV projection printing capabilities available today. This makes it ideal for the characterization of advanced resist and mask processes. The Berkeley tool also serves as a good benchmarking platform for commercial implementations of 0.3-NA EUV microsteppers because its illuminator can be programmed to emulate the coherence conditions of the commercial tools. Here we present the latest resist and tool characterization results from the Berkeley EUV exposure station

EUV microexposures at the ALS using the 0.3-NA MET projectionoptics

The recent development of high numerical aperture (NA) EUV optics such as the 0.3-NA Micro Exposure Tool (MET) optic has given rise to a new class of ultra-high resolution microexposure stations. Once such printing station has been developed and implemented at Lawrence Berkeley National Laboratory's Advanced Light Source. This flexible printing station utilizes a programmable coherence illuminator providing real-time pupil-fill control for advanced EUV resist and mask development. The Berkeley exposure system programmable illuminator enables several unique capabilities. Using dipole illumination out to {sigma}=1, the Berkeley tool supports equal-line-space printing down to 12 nm, well beyond the capabilities of similar tools. Using small-sigma illumination combined with the central obscuration of the MET optic enables the system to print feature sizes that are twice as small as those coded on the mask. In this configuration, the effective 10x-demagnification for equal lines and spaces reduces the mask fabrication burden for ultra-high-resolution printing. The illuminator facilitates coherence studies such as the impact of coherence on line-edge roughness (LER) and flare. Finally the illuminator enables novel print-based aberration monitoring techniques as described elsewhere in these proceedings. Here we describe the capabilities of the new MET printing station and present system characterization results. Moreover, we present the latest printing results obtained in experimental resists. Limited by the availability of high-resolution photoresists, equal line-space printing down to 25 nm has been demonstrated as well as isolated line printing down to 29 nm with an LER of approaching 3 nm

Physical activity characterization:Does one site fit all?

Background: It is evident that a growing number of studies advocate a wrist-worn accelerometer for the assessment of patterns of physical activity a priori, yet the veracity of this site rather than any other body-mounted location for its accuracy in classifying activity is hitherto unexplored. Objective: The objective of this review was to identify the relative accuracy with which physical activities can be classified according to accelerometer site and analytical technique. Methods: A search of electronic databases was conducted using Web of Science, PubMed and Google Scholar. This review included studies written in the English language, published between database inception and December 2017, which characterized physical activities using a single accelerometer and reported the accuracy of the technique. Results: A total of 118 articles were initially retrieved. After duplicates were removed and the remaining articles screened, 32 full-text articles were reviewed, resulting in the inclusion of 19 articles that met the eligibility criteria. Conclusion: There is no 'one site fits all' approach to the selection of accelerometer site location or analytical technique. Research design and focus should always inform the most suitable location of attachment, and should be driven by the type of activity being characterized

Preclinical and clinical evaluation of German-sourced ONC201 for the treatment of H3K27M-mutant diffuse intrinsic pontine glioma

Background Diffuse intrinsic pontine glioma (DIPG) is a fatal childhood brainstem tumor for which radiation is the only treatment. Case studies report a clinical response to ONC201 for patients with H3K27M-mutant gliomas. Oncoceutics (ONC201) is only available in the United States and Japan; however, in Germany, DIPG patients can be prescribed and dispensed a locally produced compound-ONC201 German-sourced ONC201 (GsONC201). Pediatric oncologists face the dilemma of supporting the administration of GsONC201 as conjecture surrounds its authenticity. Therefore, we compared GsONC201 to original ONC201 manufactured by Oncoceutics Inc. Methods Authenticity of GsONC201 was determined by high-resolution mass spectrometry and nuclear magnetic resonance spectroscopy. Biological activity was shown via assessment of on-target effects, in vitro growth, proliferation, and apoptosis analysis. Patient-derived xenograft mouse models were used to assess plasma and brain tissue pharmacokinetics, pharmacodynamics, and overall survival (OS). The clinical experience of 28 H3K27M+ mutant DIPG patients who received GsONC201 (2017-2020) was analyzed. Results GsONC201 harbored the authentic structure, however, was formulated as a free base rather than the dihydrochloride salt used in clinical trials. GsONC201 in vitro and in vivo efficacy and drug bioavailability studies showed no difference compared to Oncoceutics ONC201. Patients treated with GsONC201 (n = 28) showed a median OS of 18 months (P = .0007). GsONC201 patients who underwent reirradiation showed a median OS of 22 months compared to 12 months for GsONC201 patients who did not (P = .012). Conclusions This study confirms the biological activity of GsONC201 and documents the OS of patients who received the drug; however, GsONC201 was never used as a monotherapy

Analysis of Salmonella enterica Serotype Paratyphi A Gene Expression in the Blood of Bacteremic Patients in Bangladesh

Salmonella enterica serotype Paratyphi A is a significant and emerging global public health problem and accounts for one fifth of all cases of enteric fever in many areas of Asia. S. Paratyphi A only infects humans, and the lack of an appropriate animal model has limited the study of S. Paratyphi A infection. In this study, we report the application of an RNA analysis method, Selective Capture of Transcribed Sequences (SCOTS), to evaluate which S. Paratyphi A genes are expressed directly in the blood of infected humans. Our results provide insight into the bacterial adaptations and modifications that S. Paratyphi A may need to survive within infected humans and suggest that similar approaches may be applied to other pathogens in infected humans and animals