25 research outputs found
Achieving diffraction-limited performance on the Berkeley MET5
The Berkeley MET5, funded by EUREKA, is a 0.5-NA EUV projection lithography tool located at the Advanced Light Source at Berkeley National Lab. Wavefront measurements of the MET5 optic have been performed using a custom in-situ lateral shearing interferometer suitable for high-NA interferometry. In this paper, we report on the most recent characterization of the MET5 optic demonstrating an RMS wavefront 0.31 nm, and discuss the specialized mask patterns, gratings, and illumination geometries that were employed to accommodate the many challenges associated with high-NA EUV interferometry
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A project management focused framework for assuring quality work processes
Federal Manufacturing & Technologies/New Mexico (FM&T/NM) of AlliedSignal is an organization of approximately 300 associates providing operations support, engineering, and other technical services for DOE, New Mexico`s National Laboratories, etc. Work performed is primarily project-oriented and ranges from executing a major long-term contract for retrofitting and maintaining a large fleet of escort vehicles to creating a single, small, prototype electronic device for measuring radiation in a unique environment. FM&T/NM is functionally organized and operates in a classic matrix format with functional departments providing personnel with technical expertise, necessary physical resources, and administrative support to several project-based groups. Like most matrix-based organizations that provide support to diverse customers, FM&T/NM has encountered problems that occur when a group of project managers is expected to work together in using and scheduling a shared set of limited resources for the good of the organization as a whole. The framework for managing projects that we present focuses on developing, understanding, and managing the relationships between the functional organization structure, the system of work processes, and the management of projects. FM&T/NM retains its functional structure which primarily assigns personnel to work processes. The evolving role of the process leader focuses primarily on designing, managing, and improving the process, and the interactions among the subprocesses. The project manager is responsible for (1) translating customer requirements into product specifications, (2) determining the sequence of activities needed to meet project goals, (3) scheduling the required work processes, (4) monitoring project progress, (5) providing liaison between the customer and process leaders, and (6) having the desired product and/or service delivered to a satisfied customer in a timely manner
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Overview and status of the 0.5NA EUV microfield exposure tool at Berkeley Lab
A 0.5-NA extreme ultraviolet micro-field exposure tool has been installed and commissioned at beamline 12.0.1.4 of the Advanced Light Source synchrotron facility at Lawrence Berkeley National Laboratory. Commissioning has demonstrated a patterning resolution of 13 nm half-pitch with annular 0.35-0.55 illumination; a patterning resolution of 8 nm half-pitch with annular 0.1-0.2 illumination; critical dimension (CD) uniformity of 0.7 nm 1σ on 16 nm nominal CD across 80% of the 200 um x 30 um aberration corrected field of view; aerial image vibration relative to the wafer of 0.75 nn RMS and focus control and focus stepping better than 15 nm
Modulation of Clock Gene Expression by the Transcriptional Coregulator Receptor Interacting Protein 140 (RIP140)
Circadian rhythms are generated in central and peripheral tissues by an
intracellular oscillating timing mechanism known as the circadian clock. Several
lines of evidence show a strong and bidirectional interplay between metabolism
and circadian rhythms. Receptor interacting protein 140 (RIP140) is a
coregulator for nuclear receptors and other transcription factors that represses
catabolic pathways in metabolic tissues. Although RIP140 functions as a
corepressor for most nuclear receptors, mounting evidence points to RIP140 as a
dual coregulator that can repress or activate different sets of genes. Here, we
demonstrate that RIP140 mRNA and protein levels are under circadian regulation
and identify RIP140 as a modulator of clock gene expression, suggesting that
RIP140 can participate in a feedback mechanism affecting the circadian clock. We
show that the absence of RIP140 disturbs the basal levels of
BMAL1 and other clock genes, reducing the amplitude of
their oscillations. In addition, we demonstrate that RIP140 is recruited to
retinoid-related orphan receptor (ROR) binding sites on the
BMAL1 promoter, directly interacts with RORα, and
increases transcription from the BMAL1 promoter in a
RORα-dependent manner. These results indicate that RIP140 is not only
involved in metabolic control but also acts as a coactivator for RORα,
influencing clock gene expression
Live-Cell Monitoring of Periodic Gene Expression in Synchronous Human Cells Identifies Forkhead Genes involved in Cell Cycle Control
We developed a system to monitor periodic luciferase activity from cell cycle-regulated promoters in synchronous cells. Reporters were driven by a minimal human E2F1 promoter with peak expression in G1/S or a basal promoter with six Forkhead DNA-binding sites with peak expression at G2/M. After cell cycle synchronization, luciferase activity was measured in live cells at 10-min intervals across three to four synchronous cell cycles, allowing unprecedented resolution of cell cycle-regulated gene expression. We used this assay to screen Forkhead transcription factors for control of periodic gene expression. We confirmed a role for FOXM1 and identified two novel cell cycle regulators, FOXJ3 and FOXK1. Knockdown of FOXJ3 and FOXK1 eliminated cell cycle-dependent oscillations and resulted in decreased cell proliferation rates. Analysis of genes regulated by FOXJ3 and FOXK1 showed that FOXJ3 may regulate a network of zinc finger proteins and that FOXK1 binds to the promoter and regulates DHFR, TYMS, GSDMD, and the E2F binding partner TFDP1. Chromatin immunoprecipitation followed by high-throughput sequencing analysis identified 4329 genomic loci bound by FOXK1, 83% of which contained a FOXK1-binding motif. We verified that a subset of these loci are activated by wild-type FOXK1 but not by a FOXK1 (H355A) DNA-binding mutant
Retinoic Acid Mediates Long-Paced Oscillations in Retinoid Receptor Activity: Evidence for a Potential Role for RIP140
Mechanisms that underlie oscillatory transcriptional activity of nuclear receptors (NRs) are incompletely understood. Evidence exists for rapid, cyclic recruitment of coregulatory complexes upon activation of nuclear receptors. RIP140 is a NR coregulator that represses the transactivation of agonist-bound nuclear receptors. Previously, we showed that RIP140 is inducible by all-trans retinoic acid (RA) and mediates limiting, negative-feedback regulation of retinoid signaling.Here we report that in the continued presence of RA, long-paced oscillations of retinoic acid receptor (RAR) activity occur with a period ranging from 24 to 35 hours. Endogenous expression of RIP140 and other RA-target genes also oscillate in the presence of RA. Cyclic retinoid receptor transactivation is ablated by constitutive overexpression of RIP140. Further, depletion of RIP140 disrupts cyclic expression of the RA target gene HOXA5. Evidence is provided that RIP140 may limit RAR signaling in a selective, non-redundant manner in contrast to the classic NR coregulators NCoR1 and SRC1 that are not RA-inducible, do not cycle, and may be partially redundant in limiting RAR activity. Finally, evidence is provided that RIP140 can repress and be induced by other nuclear receptors in a manner that suggests potential participation in other NR oscillations.We provide evidence for novel, long-paced oscillatory retinoid receptor activity and hypothesize that this may be paced in part, by RIP140. Oscillatory NR activity may be involved in mediating hormone actions of physiological and pathological importance
Aberrant \u3ci\u3eAZIN2\u3c/i\u3e and Polyamine Metabolism Precipitates Tau Neuropathology
Tauopathies display a spectrum of phenotypes from cognitive to affective behavioral impairments; however, mechanisms promoting tau pathology and how tau elicits behavioral impairment remain unclear. We report a unique interaction between polyamine metabolism, behavioral impairment, and tau fate. Polyamines are ubiquitous aliphatic molecules that support neuronal function, axonal integrity, and cognitive processing. Transient increases in polyamine metabolism hallmark the cell’s response to various insults, known as the polyamine stress response (PSR). Dysregulation of gene transcripts associated with polyamine metabolism in Alzheimer’s disease (AD) brains were observed, and we found that ornithine decarboxylase antizyme inhibitor 2 (AZIN2) increased to the greatest extent. We showed that sustained AZIN2 overexpression elicited a maladaptive PSR in mice with underlying tauopathy (MAPT P301S; PS19). AZIN2 also increased acetylpolyamines, augmented tau deposition, and promoted cognitive and affective behavioral impairments. Higher-order polyamines displaced microtubule-associated tau to facilitate polymerization but also decreased tau seeding and oligomerization. Conversely, acetylpolyamines promoted tau seeding and oligomers. These data suggest that tauopathies launch an altered enzymatic signature that endorses a feed-forward cycle of disease progression. Taken together, the tau-induced PSR affects behavior and disease continuance, but may also position the polyamine pathway as a potential entry point for plausible targets and treatments of tauopathy, including AD
Alcohol Intake Increases in Adolescent C57BL/6J Mice during Intermittent Cycles of Phase-Delayed, Long-Light Conditions
Does the shoe fit?
Postgraduate Writing Masters Programs promise to deliver opportunities for students to develop their writing knowledge. Do these programs deliver to student expectations? Are they a success or failure? Do academic programs offer a place to teach writing? This paper explores these questions through the experiences of Masters students past and present