Microdroplet-tin plasma sources of EUV radiation driven by solid-state-lasers (Topical Review)

Plasma produced from molten-tin microdroplets generates extreme ultraviolet light for state-of-the-art nanolithography. Currently, CO2 lasers are used to drive the plasma. In the future, solid-state mid-infrared lasers may instead be used to efficiently pump the plasma. Such laser systems have promise to be more compact, better scalable, and have higher wall-plug efficiency. In this Topical Review, we present recent findings made at the Advanced Research Center for Nanolithography (ARCNL) on using 1 and 2 μm wavelength solid-state lasers for tin target preparation and for driving hot and dense plasma. The ARCNL research ranges from advanced laser development, studies of fluid dynamic response of droplets to impact, radiation-hydrodynamics calculations of, e.g. ion 'debris', (EUV) spectroscopic studies of tin laser-produced-plasma as well as high-conversion efficiency operation of 2 μm wavelength driven plasma

OrganismTagger: detection, normalization and grounding of organism entities in biomedical documents

Motivation: Semantic tagging of organism mentions in full-text articles is an important part of literature mining and semantic enrichment solutions. Tagged organism mentions also play a pivotal role in disambiguating other entities in a text, such as proteins. A high-precision organism tagging system must be able to detect the numerous forms of organism mentions, including common names as well as the traditional taxonomic groups: genus, species and strains. In addition, such a system must resolve abbreviations and acronyms, assign the scientific name and if possible link the detected mention to the NCBI Taxonomy database for further semantic queries and literature navigation. Results: We present the OrganismTagger, a hybrid rule-based/machine learning system to extract organism mentions from the literature. It includes tools for automatically generating lexical and ontological resources from a copy of the NCBI Taxonomy database, thereby facilitating system updates by end users. Its novel ontology-based resources can also be reused in other semantic mining and linked data tasks. Each detected organism mention is normalized to a canonical name through the resolution of acronyms and abbreviations and subsequently grounded with an NCBI Taxonomy database ID. In particular, our system combines a novel machine-learning approach with rule-based and lexical methods for detecting strain mentions in documents. On our manually annotated OT corpus, the OrganismTagger achieves a precision of 95%, a recall of 94% and a grounding accuracy of 97.5%. On the manually annotated corpus of Linnaeus-100, the results show a precision of 99%, recall of 97% and grounding accuracy of 97.4%. Availability: The OrganismTagger, including supporting tools, resources, training data and manual annotations, as well as end user and developer documentation, is freely available under an open-source license at http://www.semanticsoftware.info/organism-tagger. Contact: [email protected]

Intracisternal delivery of NFκB-inducible scAAV2/9 reveals locoregional neuroinflammation induced by systemic kainic acid treatment.

We have previously demonstrated disease-dependent gene delivery in the brain using an AAV vector responding to NFκB activation as a probe for inflammatory responses. This vector, injected focally in the parenchyma prior to a systemic kainic acid (KA) injection mediated inducible transgene expression in the hippocampus but not in the cerebellum, regions, respectively, known to be affected or not by the pathology. However, such a focal approach relies on previous knowledge of the model parameters and does not allow to predict the whole brain response to the disease. Global brain gene delivery would allow to predict the regional distribution of the pathology as well as to deliver therapeutic factors in all affected brain regions. We show that self-complementary AAV2/9 (scAAV2/9) delivery in the adult rat cisterna magna allows a widespread but not homogenous transduction of the brain. Indeed, superficial regions, i.e., cortex, hippocampus, and cerebellum were more efficiently transduced than deeper regions, such as striatum, and substantia nigra. These data suggest that viral particles penetration from the cerebrospinal fluid (CSF) into the brain is a limiting factor. Interestingly, AAV2/9-2YF a rationally designed capsid mutant (affecting surface tyrosines) increased gene transfer efficiency approximately fivefold. Neurons, astrocytes, and oligodendrocytes, but not microglia, were transduced in varying proportions depending on the brain region and the type of capsid. Finally, after a single intracisternal injection of scAAV2/9-2YF using the NFκB-inducible promoter, KA treatment induced transgene expression in the hippocampus and cortex but not in the cerebellum, corresponding to the expression of the CD11b marker of microglial activation. These data support the use of disease-inducible vectors administered in the cisterna magna as a tool to characterize the brain pathology in systemic drug-induced or transgenic disease models. However, further improvements are required to enhance viral particles penetration into the brain

Ion distribution and ablation depth measurements of a fs-ps laser-irradiated solid tin target

The ablation of solid tin surfaces by an 800-nanometer-wavelength laser is studied for a pulse length range from 500 fs to 4.5 ps and a fluence range spanning 0.9 to 22 J/cm^2. The ablation depth and volume are obtained employing a high-numerical-aperture optical microscope, while the ion yield and energy distributions are obtained from a set of Faraday cups set up under various angles. We found a slight increase of the ion yield for an increasing pulse length, while the ablation depth is slightly decreasing. The ablation volume remained constant as a function of pulse length. The ablation depth follows a two-region logarithmic dependence on the fluence, in agreement with the available literature and theory. In the examined fluence range, the ion yield angular distribution is sharply peaked along the target normal at low fluences but rapidly broadens with increasing fluence. The total ionization fraction increases monotonically with fluence to a 5-6% maximum, which is substantially lower than the typical ionization fractions obtained with nanosecond-pulse ablation. The angular distribution of the ions does not depend on the laser pulse length within the measurement uncertainty. These results are of particular interest for the possible utilization of fs-ps laser systems in plasma sources of extreme ultraviolet light for nanolithography.Comment: 8 pages, 7 figure

Boundary conditions associated with the Painlev\'e III' and V evaluations of some random matrix averages

In a previous work a random matrix average for the Laguerre unitary ensemble, generalising the generating function for the probability that an interval $(0,s)$ at the hard edge contains $k$ eigenvalues, was evaluated in terms of a Painlev\'e V transcendent in $\sigma$-form. However the boundary conditions for the corresponding differential equation were not specified for the full parameter space. Here this task is accomplished in general, and the obtained functional form is compared against the most general small $s$ behaviour of the Painlev\'e V equation in $\sigma$-form known from the work of Jimbo. An analogous study is carried out for the the hard edge scaling limit of the random matrix average, which we have previously evaluated in terms of a Painlev\'e \IIId transcendent in $\sigma$-form. An application of the latter result is given to the rapid evaluation of a Hankel determinant appearing in a recent work of Conrey, Rubinstein and Snaith relating to the derivative of the Riemann zeta function

Assessment of Interspecies Differences in Drug-Induced QTc Interval Prolongation in Cynomolgus Monkeys, Dogs and Humans.

BACKGROUND AND PURPOSE The selection of the most suitable animal species and subsequent translation of the concentration-effect relationship to humans are critical steps for accurate assessment of the pro-arrhythmic risk of candidate molecules. The objective of this investigation was to assess quantitatively the differences in the QTc prolonging effects of moxifloxacin between cynomolgus monkeys, dogs and humans. The impact of interspecies differences is also illustrated for a new candidate molecule. EXPERIMENTAL APPROACH Pharmacokinetic data and ECG recordings from pre-clinical protocols in monkeys and dogs and from a phase I trial in healthy subjects were identified for the purpose of this analysis. A previously established Bayesian model describing the combined effect of heart rate, circadian variation and drug effect on the QT interval was used to describe the pharmacokinetic-pharmacodynamic relationships. The probability of a ≥ 10 ms increase in QT was derived as measure of the pro-arrhythmic effect. KEY RESULTS For moxifloxacin, the concentrations associated with a 50% probability of QT prolongation ≥ 10 ms (Cp50) varied from 20.3 to 6.4 and 2.6 μM in dogs, monkeys and humans, respectively. For NCE05, these values were 0.4 μM vs 2.0 μM for monkeys and humans, respectively. CONCLUSIONS AND IMPLICATIONS Our findings reveal significant interspecies differences in the QT-prolonging effect of moxifloxacin. In addition to the dissimilarity in pharmacokinetics across species, it is likely that differences in pharmacodynamics also play an important role. It appears that, regardless of the animal model used, a translation function is needed to predict concentration-effect relationships in humans