Method for fabricating a low stress x-ray mask using annealable amorphous refractory compounds

X‐ray masks have been fabricated by depositing a compressively stressed refractory material on a wafer, annealing to a zero stress state, and then forming the membrane. Amorphous TaSiN and TaSi alloys deposited with a magnetron sputter tool have been extensively characterized in terms of resistivity, composition, defectivity, surface roughness, and crystalline state. Optimization in terms of these parameters has resulted in base line selection of absorber films of the following compositions: Ta_(61)Si_(17)N_(21) and Ta_(75)Si_(23). The process is shown to be extendable to an entire class of amorphous annealable refractory materials. Careful studies of deposition and annealing conditions have resulted in a 4× reduction of image placement to the 30 nm maximum vector level. Finally, the importance of stress gradients is experimentally verified

FHF2 isoforms differentially regulate Nav1.6-mediated resurgent sodium currents in dorsal root ganglion neurons

Nav1.6 and Nav1.6-mediated resurgent currents have been implicated in several pain pathologies. However, our knowledge of how fast resurgent currents are modulated in neurons is limited. Our study explored the potential regulation of Nav1.6-mediated resurgent currents by isoforms of fibroblast growth factor homologous factor 2 (FHF2) in an effort to address the gap in our knowledge. FHF2 isoforms colocalize with Nav1.6 in peripheral sensory neurons. Cell line studies suggest that these proteins differentially regulate inactivation. In particular, FHF2A mediates long-term inactivation, a mechanism proposed to compete with the open-channel blocker mechanism that mediates resurgent currents. On the other hand, FHF2B lacks the ability to mediate long-term inactivation and may delay inactivation favoring open-channel block. Based on these observations, we hypothesized that FHF2A limits resurgent currents, whereas FHF2B enhances resurgent currents. Overall, our results suggest that FHF2A negatively regulates fast resurgent current by enhancing long-term inactivation and delaying recovery. In contrast, FHF2B positively regulated resurgent current and did not alter long-term inactivation. Chimeric constructs of FHF2A and Navβ4 (likely the endogenous open channel blocker in sensory neurons) exhibited differential effects on resurgent currents, suggesting that specific regions within FHF2A and Navβ4 have important regulatory functions. Our data also indicate that FHFAs and FHF2B isoform expression are differentially regulated in a radicular pain model and that associated neuronal hyperexcitability is substantially attenuated by a FHFA peptide. As such, these findings suggest that FHF2A and FHF2B regulate resurgent current in sensory neurons and may contribute to hyperexcitability associated with some pain pathologies

Mars Science Helicopter Conceptual Design

Robotic planetary aerial vehicles increase the range of terrain that can be examined, compared to traditional landers and rovers, and have more near-surface capability than orbiters. Aerial mobility is a promising possibility for planetary exploration as it reduces the challenges that difficult obstacles pose to ground vehicles. The first use of a rotorcraft for a planetary mission will be in 2021, when the Mars Helicopter technology demonstrator will be deployed from the Mars 2020 rover. The Jet Propulsion Laboratory and NASA Ames Research Center are exploring possibilities for a Mars Science Helicopter, a second-generation Mars rotorcraft with the capability of conducting science investigations independently of a lander or rover (although this type of vehicle could also be used assist rovers or landers in future missions). This report describes the conceptual design of Mars Science Helicopters. The design process began with coaxial-helicopter and hexacopter configurations, with a payload in the range of two to three kilograms and an overall vehicle mass of approximately twenty kilograms. Initial estimates of weight and performance were based on the capabilities of the Mars Helicopter. Rotorcraft designs for Mars are constrained by the dimensions of the aeroshell for the trip to the planet, requiring attention to the aircraft packaging in order to maximize the rotor dimensions and hence overall performance potential. Aerodynamic performance optimization was conducted, particularly through airfoils designed specifically for the low Reynolds number and high Mach number inherent in operation on Mars. The final designs show a substantial capability for science operations on Mars: a 31 kg hexacopter that fits within a 2.5 m diameter aeroshell could carry a 5 kg payload for 10 min of hover time or over a range of 5 km

Evidence to inform occupational therapy intervention with adults with intellectual disability: A scoping review

Importance: Occupational therapy practitioners use a range of habilitative and compensatory approaches to teach new skills or modify tasks and environments to address occupational performance among adults with intellectual disability (ID); therefore, they must identify and use available evidence to guide intervention planning. Objective: To summarize the scope of evidence that can inform occupational therapy intervention with adults with primary or comorbid ID. Data Sources: Articles published in peer-reviewed journals between January 2002 and January 2018 and indexed in PubMed, CINAHL, PsycINFO, and Scopus. Study Selection and Data Collection: A total of 159 articles met inclusion criteria and contained information on occupational therapy intervention with adults ages 18 yr or older with primary or coexisting ID. Findings: Fifty-seven of the 159 articles focused on intervention to address occupational performance outcomes (i.e., employment, self-care, leisure and social interaction, community participation). Conclusions and Relevance: A wide range of literature is available to support occupational therapy intervention with adults with ID. Occupational therapy practitioners may be less knowledgeable about this evidence because much of it is located in non-occupational therapy or international journals

Calcium/Calmodulin-Dependent Protein Kinase II Regulation of IKs during Sustained Beta-Adrenergic Receptor Stimulation

Background Sustained β-adrenergic receptor (β-AR) stimulation causes pathophysiological changes during heart failure (HF), including inhibition of the slow component of the delayed rectifier potassium current (IKs). Aberrant calcium handling, including increased activation of calcium/calmodulin-dependent protein kinase II (CaMKII), contributes to arrhythmia development during HF. Objective The purpose of this study was to investigate CaMKII regulation of KCNQ1 (pore-forming subunit of IKs) during sustained β-AR stimulation and associated functional implications on IKs. Methods KCNQ1 phosphorylation was assessed using LCMS/MS after sustained β-AR stimulation with isoproterenol (ISO). Peptide fragments corresponding to KCNQ1 residues were synthesized to identify CaMKII phosphorylation at the identified sites. Dephosphorylated (alanine) and phosphorylated (aspartic acid) mimics were introduced at identified residues. Whole-cell, voltage-clamp experiments were performed in human endothelial kidney 293 cells coexpressing wild-type or mutant KCNQ1 and KCNE1 (auxiliary subunit) during ISO treatment or lentiviral δCaMKII overexpression. Results Novel KCNQ1 carboxy-terminal sites were identified with enhanced phosphorylation during sustained β-AR stimulation at T482 and S484. S484 peptides demonstrated the strongest δCaMKII phosphorylation. Sustained β-AR stimulation reduced IKs activation (P = .02 vs control) similar to the phosphorylated mimic (P = .62 vs sustained β-AR). Individual phosphorylated mimics at S484 (P = .04) but not at T482 (P = .17) reduced IKs function. Treatment with CN21 (CaMKII inhibitor) reversed the reductions in IKs vs CN21-Alanine control (P < .01). δCaMKII overexpression reduced IKs similar to ISO treatment in wild type (P < .01) but not in the dephosphorylated S484 mimic (P = .99). Conclusion CaMKII regulates KCNQ1 at S484 during sustained β-AR stimulation to inhibit IKs. The ability of CaMKII to inhibit IKs may contribute to arrhythmogenicity during HF

Chemical Reaction Dynamics at Surfaces

Contains reports on three research projects.Joint Services Electronics Program Contract DAAL03-89-C-0001Joint Services Electronics Program Contract DAAL03-92-C-0001National Science Foundation Grant CHE 90-2062

Ligand and Receptor Dynamics Contribute to the Mechanism of Graded PPARγ Agonism

SummaryLigand binding to proteins is not a static process, but rather involves a number of complex dynamic transitions. A flexible ligand can change conformation upon binding its target. The conformation and dynamics of a protein can change to facilitate ligand binding. The conformation of the ligand, however, is generally presumed to have one primary binding mode, shifting the protein conformational ensemble from one state to another. We report solution nuclear magnetic resonance (NMR) studies that reveal peroxisome proliferator-activated receptor γ (PPARγ) modulators can sample multiple binding modes manifesting in multiple receptor conformations in slow conformational exchange. Our NMR, hydrogen/deuterium exchange and docking studies reveal that ligand-induced receptor stabilization and binding mode occupancy correlate with the graded agonist response of the ligand. Our results suggest that ligand and receptor dynamics affect the graded transcriptional output of PPARγ modulators

Shifts in the Fecal Microbiota Associated with Adenomatous Polyps

BACKGROUND: Adenomatous polyps are the most common precursor to colorectal cancer, the second leading cause of cancer-related death in the United States. We sought to learn more about early events of carcinogenesis by investigating shifts in the gut microbiota of patients with adenomas. METHODS: We analyzed 16S rRNA gene sequences from the fecal microbiota of patients with adenomas (n = 233) and without (n = 547). RESULTS: Multiple taxa were significantly more abundant in patients with adenomas, including Bilophila, Desulfovibrio, proinflammatory bacteria in the genus Mogibacterium, and multiple Bacteroidetes species. Patients without adenomas had greater abundances of Veillonella, Firmicutes (Order Clostridia), and Actinobacteria (family Bifidobacteriales). Our findings were consistent with previously reported shifts in the gut microbiota of colorectal cancer patients. Importantly, the altered adenoma profile is predicted to increase primary and secondary bile acid production, as well as starch, sucrose, lipid, and phenylpropanoid metabolism. CONCLUSIONS: These data hint that increased sugar, protein, and lipid metabolism along with increased bile acid production could promote a colonic environment that supports the growth of bile-tolerant microbes such as Bilophilia and Desulfovibrio In turn, these microbes may produce genotoxic or inflammatory metabolites such as H2S and secondary bile acids, which could play a role in catalyzing adenoma development and eventually colorectal cancer. IMPACT: This study suggests a plausible biological mechanism to explain the links between shifts in the microbiota and colorectal cancer. This represents a first step toward resolving the complex interactions that shape the adenoma-carcinoma sequence of colorectal cancer and may facilitate personalized therapeutics focused on the microbiota

Analytic Quantization of the QCD String

We perform an analytic semi-classical quantization of the straight QCD string with one end fixed and a massless quark on the other, in the limits of orbital and radial dominant motion. We compare our results to the exact numerical semi-classical quantization. We observe that the numerical semi-classical quantization agrees well with our exact numerical canonical quantization.Comment: RevTeX, 10 pages, 9 figure