57 research outputs found
Visualization of HIV-1 interactions with penile and foreskin epithelia: clues for female-to-male HIV transmission
To gain insight into female-to-male HIV sexual transmission and how male circumcision protects against this mode of transmission, we visualized HIV-1 interactions with foreskin and penile tissues in ex vivo tissue culture and in vivo rhesus macaque models utilizing epifluorescent microscopy. 12 foreskin and 14 cadaveric penile specimens were cultured with R5-tropic photoactivatable (PA)-GFP HIV-1 for 4 or 24 hours. Tissue cryosections were immunofluorescently imaged for epithelial and immune cell markers. Images were analyzed for total virions, proportion of penetrators, depth of virion penetration, as well as immune cell counts and depths in the tissue. We visualized individual PA virions breaching penile epithelial surfaces in the explant and macaque model. Using kernel density estimated probabilities of localizing a virion or immune cell at certain tissue depths revealed that interactions between virions and cells were more likely to occur in the inner foreskin or glans penis (from local or cadaveric donors, respectively). Using statistical models to account for repeated measures and zero-inflated datasets, we found no difference in total virions visualized at 4 hours between inner and outer foreskins from local donors. At 24 hours, there were more virions in inner as compared to outer foreskin (0.0495 +/- 0.0154 and 0.0171 +/- 0.0038 virions/image, p = 0.001). In the cadaveric specimens, we observed more virions in inner foreskin (0.0507 +/- 0.0079 virions/image) than glans tissue (0.0167 +/- 0.0033 virions/image, p<0.001), but a greater proportion was seen penetrating uncircumcised glans tissue (0.0458 +/- 0.0188 vs. 0.0151 +/- 0.0100 virions/image, p = 0.099) and to significantly greater mean depths (29.162 +/- 3.908 vs. 12.466 +/- 2.985 μm). Our in vivo macaque model confirmed that virions can breach penile squamous epithelia in a living model. In summary, these results suggest that the inner foreskin and glans epithelia may be important sites for HIV transmission in uncircumcised men
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Fabrication of Beryllium Capsules with Copper-Doped Layers for NIF Targets: A Progress Report
The sputtering of beryllium (Be) has been used at LLNL for nearly 30 years in the fabrication of laser targets. Several years ago the prospect of using sputtering to fabricate spherical Be capsules for National Ignition Facility (NIF) targets began to be explored and a basic strategy was developed that involved sputtering down onto plastic mandrels bouncing in a pan. While this appears to be very straightforward in principle, in practice sputtering has been used almost exclusively to make thin films (< 1 micron) on flat substrates. Thick films pose a significant challenge for sputtering while materials on spherical substrates are essentially unexplored. More recently, based on computational results, the point design for the first NIF ignition target capsule was specified as a Be capsule with Cu-doped layers of specific thickness, each layer with a different concentration of copper. While the work described here was motivated by the need to make the layered capsules, the primary progress on Be capsules has been the development of a more complete metallurgical understanding of the materials that are fabricated and the beginning of the exploration of the relationship between the sputter processing and microstructure of these spherical samples. At least two barriers to growth to full thickness (i.e. 170 microns) have been identified and efforts to overcome these barriers are underway
Original research: longitudinal evaluation of cognitively demanding daily function using performance-based functional assessment highlights heterogeneous trajectories in cognitive and functional abilities in people with Parkinson’s disease
BackgroundLongitudinal assessment of functional abilities in Parkinson’s disease (PD) is needed to determine the efficacy of cognitive interventions in providing meaningful improvements in daily life. Additionally, subtle changes in instrumental activities of daily living may precede a clinical diagnosis of dementia and could aid earlier detection of and intervention for cognitive decline.ObjectiveThe primary goal was to validate the longitudinal application of the University of California San Diego Performance-Based Skills Assessment (UPSA). An exploratory secondary goal was to determine whether UPSA may identify individuals at higher risk of cognitive decline in PD.MethodsSeventy participants with PD completed the UPSA with at least one follow-up visit. Linear mixed effects modeling was used to identify associations between baseline UPSA score and cognitive composite score (CCS) over time. Descriptive analysis of four heterogeneous cognitive and functional trajectory groups and individual case examples was performed.ResultsBaseline UPSA score predicted CCS at each timepoint for functionally impaired and unimpaired groups (p < 0.01) but did not predict the rate change in CCS over time (p = 0.83). Participants displayed heterogenous trajectories in both UPSA and CCS during the follow-up period. Most participants maintained both cognitive and functional performance (n = 54), though some displayed cognitive and functional decline (n = 4), cognitive decline with functional maintenance (n = 4), and functional decline with cognitive maintenance (n = 8).ConclusionThe UPSA is a valid measure of cognitive functional abilities over time in PD. Given the heterogeneity of functional and cognitive trajectories, this performance-based assessment did not predict cognitive decline with this relatively short follow-up. Further work is needed to understand longitudinal functional assessments in PD-associated cognitive impairment
Context, cognition and communication in language
Questions pertaining to the unique structure and organisation of language have a
long history in the field of linguistics. In recent years, researchers have explored
cultural evolutionary explanations, showing how language structure emerges from
weak biases amplified over repeated patterns of learning and use. One outstanding
issue in these frameworks is accounting for the role of context. In particular,
many linguistic phenomena are said to to be context-dependent; interpretation
does not take place in a void, and requires enrichment from the current state
of the conversation, the physical situation, and common knowledge about the
world. Modelling the relationship between language structure and context is
therefore crucial for developing a cultural evolutionary approach to language.
One approach is to use statistical analyses to investigate large-scale, cross-cultural
datasets. However, due to the inherent limitations of statistical analyses, especially
with regards to the inadequacy of these methods to test hypotheses about
causal relationships, I argue that experiments are better suited to address questions
pertaining to language structure and context. From here, I present a series
of artificial language experiments, with the central aim being to test how
manipulations to context influence the structure and organisation of language.
Experiment 1 builds upon previous work in iterated learning and communication
games through demonstrating that the emergence of optimal communication systems
is contingent on the contexts in which languages are learned and used. The
results show that language systems gradually evolve to only encode information
that is informative for conveying the intended meaning of the speaker - resulting
in markedly different systems of communication. Whereas Experiment 1 focused
on how context influences the emergence of structure, Experiments 2 and 3 investigate
under what circumstances do manipulations to context result in the loss
of structure. While the results are inconclusive across these two experiments,
there is tentative evidence that manipulations to context can disrupt structure,
but only when interacting with other factors. Lastly, Experiment 4 investigates
whether the degree of signal autonomy (the capacity for a signal to be interpreted without recourse to contextual information) is shaped by manipulations
to contextual predictability: the extent to which a speaker can estimate and exploit
contextual information a hearer uses in interpreting an utterance. When
the context is predictable, speakers organise languages to be less autonomous
(more context-dependent) through combining linguistic signals with contextual
information to reduce effort in production and minimise uncertainty in comprehension.
By decreasing contextual predictability, speakers increasingly rely on
strategies that promote more autonomous signals, as these signals depend less on
contextual information to discriminate between possible meanings. Overall, these
experiments provide proof-of-concept for investigating the relationship between
language structure and context, showing that the organisational principles underpinning
language are the result of competing pressures from context, cognition,
and communication
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Extreme Ultraviolet Lithography - Reflective Mask Technology
EUVL mask blanks consist of a distributed Bragg reflector made of 6.7nm-pitch bi-layers of MO and Si deposited upon a precision Si or glass substrate. The layer deposition process has been optimized for low defects, by application of a vendor-supplied but highly modified ion-beam sputter deposition system. This system is fully automated using SMIF technology to obtain the lowest possible environmental- and handling-added defect levels. Originally designed to coat 150mm substrates, it was upgraded in July, 1999 to 200 mm and has coated runs of over 50 substrates at a time with median added defects >100nm below 0.05/cm{sup 2}. These improvements have resulted from a number of ion-beam sputter deposition system modifications, upgrades, and operational changes, which will be discussed. Success in defect reduction is highly dependent upon defect detection, characterization, and cross-platform positional registration. We have made significant progress in adapting and extending commercial tools to this purpose, and have identified the surface scanner detection limits for different defect classes, and the signatures of false counts and non-printable scattering anomalies on the mask blank. We will present key results and how they have helped reduce added defects. The physics of defect reduction and mitigation is being investigated by a program on multilayer growth over deliberately placed perturbations (defects) of varying size. This program includes modeling of multilayer growth and modeling of defect printability. We developed a technique for depositing uniformly sized gold spheres on EUVL substrates, and have studied the suppression of the perturbations during multilayer growth under varying conditions. This work is key to determining the lower limit of critical defect size for EUV Lithography. We present key aspects of this work. We will summarize progress in all aspects of EUVL mask blank development, and present detailed results on defect reduction and mask blank performance at EUV wavelengths
Characterization of Silicon Nanocrystal Surfaces by Multidimensional Solid-State NMR Spectroscopy
The chemical and
photophysical properties of silicon nanocrystals
(Si NCs) are strongly dependent on the chemical composition and structure
of their surfaces. Here we use fast magic angle spinning (MAS) and
proton detection to enable the rapid acquisition of dipolar and scalar
2D <sup>1</sup>H–<sup>29</sup>Si heteronuclear correlation
(HETCOR) solid-state NMR spectra and reveal a molecular picture of
hydride-terminated and alkyl-functionalized surfaces of Si NCs produced
in a nonthermal plasma. 2D <sup>1</sup>H–<sup>29</sup>Si HETCOR
and dipolar 2D <sup>1</sup>H–<sup>1</sup>H multiple-quantum
correlation spectra illustrate that resonances from surface mono-,
di-, and trihydride groups cannot be resolved, contrary to previous
literature assignments. Instead the 2D NMR spectra illustrate that
there is large distribution of <sup>1</sup>H and <sup>29</sup>Si chemical
shifts for the surface hydride species in both the as-synthesized
and functionalized Si NCs. However, proton-detected <sup>1</sup>H–<sup>29</sup>Si refocused INEPT experiments can be used to unambiguously
differentiate NMR signals from the different surface hydrides. Varying
the <sup>29</sup>Si evolution time in refocused INEPT experiments
and fitting the oscillation of the NMR signals allows for the relative
populations of the different surface hydrides to be estimated. This
analysis confirms that monohydride species are the predominant surface
species on the as-synthesized Si NCs. A reduction in the populations
of the di- and trihydrides is observed upon functionalization with
alkyl groups, consistent with our previous hypothesis that the trihydride,
or silyl (*SiH<sub>3</sub>), group is primarily responsible for initiating
surface functionalization reactions. Density functional theory (DFT)
calculations were used to obtain quantum chemical structural models
of the Si NC surface and reproduce the observed <sup>1</sup>H and <sup>29</sup>Si chemical shifts. The approaches outlined here will be
useful to obtain a more detailed picture of surface structures for
Si NCs and other hydride-passivated nanomaterials
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