Engineering Papers⌕ Search

SEARCH · Engineering Papers

Results for “Shared Responsibility”

Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 613 records · Page 34
All sourcesNASA NTRSDOE OSTI
DOE OSTI2012

Characterization of the Early CNS Stress Biomarkers and Profiles Associated with Neuropsychiatric Diseases

Neuropsychiatric disorders (including dementia) have high personal, family, and social costs. Although many neuropsychiatric disorders share common patterns of symptoms and treatments, there are no validated biomarkers that define the underlying molecular mechanisms in the central nervous system (CNS). We hypothesize that there are early and common molecular changes in the CNS that will serve as sensitive indicators of CNS molecular stress and that will be predictive of neuropathological changes resulted in increasing the risk for neuropsychiatric diseases. Using the rodent model, we showed that systemic exposure to three diverse CNS stressors with different mechanisms of action (ketamine, low-dose and high-dose ionizing radiation, interferon-) induced the expression of troponin T1 (Tnnt 1) within hours in adult mouse brain tissue. Tnnt 1 expression was induced in neuronal (not glial) cells, the hippocampal zone of neurogenesis, cerebral cortex, amygdale, and choroid plexus, which are important CNS locations in behavior and mental health. We also identified nine neural signaling pathways that showed a high degree of concordance in their transcriptional response in mouse brain tissue for hours after low-dose irradiation, in the aging human brain (unirradiated), and in brain tissue from patients with Alzheimer’s disease. Our studies provide new molecular information on shared mechanisms and expression profiles of diverse neuropsychiatric disorders. This knowledge will be fundamental for developing molecular signatures of early CNS stress biomarker for early diagnosis and treatment of neuropsychiatric diseases.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2022

Pseudouridine synthase 7 is an opportunistic enzyme that binds and modifies substrates with diverse sequences and structures

Pseudouridine (Ψ) is a ubiquitous RNA modification incorporated by pseudouridine synthase (Pus) enzymes into hundreds of noncoding and protein-coding RNA substrates. Here, in this study, we determined the contributions of substrate structure and protein sequence to binding and catalysis by pseudouridine synthase 7 (Pus7), one of the principal messenger RNA (mRNA) modifying enzymes. Pus7 is distinct among the eukaryotic Pus proteins because it modifies a wider variety of substrates and shares limited homology with other Pus family members. We solved the crystal structure of Saccharomyces cerevisiae Pus7, detailing the architecture of the eukaryotic-specific insertions thought to be responsible for the expanded substrate scope of Pus7. Additionally, we identified an insertion domain in the protein that fine-tunes Pus7 activity both in vitro and in cells. These data demonstrate that Pus7 preferentially binds substrates possessing the previously identified UGUAR (R = purine) consensus sequence and that RNA secondary structure is not a strong requirement for Pus7-binding. In contrast, the rate constants and extent of Ψ incorporation are more influenced by RNA structure, with Pus7 modifying UGUAR sequences in less-structured contexts more efficiently both in vitro and in cells. Although less-structured substrates were preferred, Pus7 fully modified every transfer RNA, mRNA, and nonnatural RNA containing the consensus recognition sequence that we tested. Our findings suggest that Pus7 is a promiscuous enzyme and lead us to propose that factors beyond inherent enzyme properties (e.g., enzyme localization, RNA structure, and competition with other RNA-binding proteins) largely dictate Pus7 substrate selection.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2021

Multidimensional genome-wide screening in yeast provides mechanistic insights into europium toxicity

Abstract Europium is a lanthanide metal that is highly valued in optoelectronics. Even though europium is used in many commercial products, its toxicological profile has only been partially characterized, with most studies focusing on identifying lethal doses in different systems or bioaccumulation in vivo. This paper describes a genome-wide toxicogenomic study of europium in Saccharomyces cerevisiae, which shares many biological functions with humans. By using a multidimensional approach and functional and network analyses, we have identified a group of genes and proteins associated with the yeast responses to ameliorate metal toxicity, which include metal discharge paths through vesicle-mediated transport, paths to regulate biologically relevant cations, and processes to reduce metal-induced stress. Furthermore, the analyses indicated that europium promotes yeast toxicity by disrupting the function of chaperones and cochaperones, which have metal-binding sites. Several of the genes and proteins highlighted in our study have human orthologues, suggesting they may participate in europium-induced toxicity in humans. By identifying the endogenous targets of europium as well as the already existing paths that can decrease its toxicity, we can determine specific genes and proteins that may help to develop future therapeutic strategies.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2022

SARS-CoV-2 Beta variant infection elicits potent lineage-specific and cross-reactive antibodies

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Beta variant of concern (VOC) resists neutralization by major classes of antibodies from COVID-19 patients and vaccinated individuals. In this study, serum of Beta-infected patients revealed reduced cross-neutralization of wild-type virus. From these patients, we isolated Beta-specific and cross-reactive receptor-binding domain (RBD) antibodies. The Beta-specificity results from recruitment of VOC-specific clonotypes and accommodation of mutations present in Beta and Omicron into a major antibody class that is normally sensitive to these mutations. The Beta-elicited cross-reactive antibodies share genetic and structural features with wild type–elicited antibodies, including a public VH1-58 clonotype that targets the RBD ridge. These findings advance our understanding of the antibody response to SARS-CoV-2 shaped by antigenic drift, with implications for design of next-generation vaccines and therapeutics.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2022

Waveform Data Quality Assessment

Healthy seismoacoustic sensors and accurate metadata are critical to all the science objectives of both the Source Physics Experiment (SPE) Rock Valley Direct Comparison (RV/DC) and LowYield Physics Experiment-1 (LYNM PE-1). Both projects share similar seismoacoustic stations. We provide a plan on how to move forward with waveform data quality assessments (QA) to the working groups. The identification of stations with instrument response errors will be useful to researchers using amplitudes to study source effects and Earth attenuation. The data QA can also be useful for field technicians to help identify and correct problem sites.

47 OTHER INSTRUMENTATION↗
DOE OSTI2025

Parallel Runtime Interface for Fortran (PRIF) Specification (Rev. 0.6)

This document specifies an interface to support the multi-image parallelism features of Fortran, named the Parallel Runtime Interface for Fortran (PRIF). PRIF is a solution in which a runtime library is primarily responsible for implementing coarray allocation, deallocation and accesses, image synchronization, atomic operations, events, teams and collective subroutines. The Fortran compiler is responsible for transforming the invocation of Fortran-level multi-image parallelism features into procedure calls to the necessary PRIF subroutines. The interface is designed for portability across shared- and distributed-memory machines, different operating systems, and multiple architectures. Implementations of this interface are intended as an augmentation for the compiler's own runtime library. With an implementation-agnostic interface, alternative parallel runtime libraries may be developed that support the same interface. One benefit of this approach is the ability to vary the communication substrate. A central aim of this document is to define a parallel runtime interface in standard Fortran syntax, which enables us to leverage Fortran to succinctly express various properties of the procedure interfaces, including argument attributes.

97 MATHEMATICS AND COMPUTING↗
NASA NTRS1985

Interactions among sulfide-oxidizing bacteria

The responses of different phototrophic bacteria in a competitive experimental system are studied, one in which primary factors such as H2S or light limited photometabolism. Two different types of bacteria shared one limited source of sulfide under specific conditions of light. The selection of a purple and a green sulfur bacteria and the cyanobacterium was based on their physiological similarity and also on the fact that they occur together in microbial mats. They all share anoxygenic photosynthesis, and are thus probably part of an evolutionary continuum of phototrophic organisms that runs from, strictly anaerobic physiology to the ability of some cyanobacteria to shift between anoxygenic bacterial style photosynthesis and the oxygenic kind typical of eukaryotes.

Poplawski, R.↗
NASA NTRS1999

Aerospace Engineering Systems and the Advanced Design Technologies Testbed Experience

Continuous improvement of aerospace product development processes is a driving requirement across much of the aerospace community. As up to 90% of the cost of an aerospace product is committed during the first 10% of the development cycle, there is a strong emphasis on capturing, creating, and communicating better information (both requirements and performance) early in the product development process. The community has responded by pursuing the development of computer-based systems designed to enhance the decision-making capabilities of product development individuals and teams. Recently, the historical foci on sharing the geometrical representation and on configuration management are being augmented: 1) Physics-based analysis tools for filling the design space database; 2) Distributed computational resources to reduce response time and cost; 3) Web-based technologies to relieve machine-dependence; and 4) Artificial intelligence technologies to accelerate processes and reduce process variability. The Advanced Design Technologies Testbed (ADTT) activity at NASA Ames Research Center was initiated to study the strengths and weaknesses of the technologies supporting each of these trends, as well as the overall impact of the combination of these trends on a product development event. Lessons learned and recommendations for future activities are reported.

VanDalsem, William R.↗
NASA NTRS2004

HEC Applications on Columbia Project

NASA's Columbia system consists of a cluster of twenty 512 processor SGI Altix systems. Each of these systems is 3 TFLOP/s in peak performance - approximately the same as the entire compute capability at NAS just one year ago. Each 512p system is a single system image machine with one Linunx O5, one high performance file system, and one globally shared memory. The NAS Terascale Applications Group (TAG) is chartered to assist in scaling NASA's mission critical codes to at least 512p in order to significantly improve emergency response during flight operations, as well as provide significant improvements in the codes. and rate of scientific discovery across the scientifc disciplines within NASA's Missions. Recent accomplishments are 4x improvements to codes in the ocean modeling community, 10x performance improvements in a number of computational fluid dynamics codes used in aero-vehicle design, and 5x improvements in a number of space science codes dealing in extreme physics. The TAG group will continue its scaling work to 2048p and beyond (10240 cpus) as the Columbia system becomes fully operational and the upgrades to the SGI NUMAlink memory fabric are in place. The NUMlink uprades dramatically improve system scalability for a single application. These upgrades will allow a number of codes to execute faster at higher fidelity than ever before on any other system, thus increasing the rate of scientific discovery even further

Taft, Jim↗
NASA NTRS2016

Managing a Safe and Successful Multi-User Spaceport

Encouraged by the creation of the Office of Commercial Space Transportation within the U.S. Federal Aviation Administration (FAA) in 1984 and the Commercial Space Act of 1998, the National Aeronautics and Space Administration (NASA) now relies on an extensive network of support from commercial companies and organizations. At NASA's Kennedy Space Center (KSC), this collaboration opens competitive opportunities for launch providers, including repurposing underutilized Shuttle Program resources, constructing new facilities, and utilizing center services and laboratories. The resulting multi-user spaceport fosters diverse activity, though it engenders risk from hazards associated with various spaceflight processing activities. The KSC Safety & Mission Assurance (S&MA) Directorate, in coordination with the center's Spaceport Integration and Center Planning & Development organizations, has developed a novel approach to protect NASA's workforce, critical assets, and the public from hazardous, space-related activity associated with KSC's multi-user spaceport. For NASA KSC S&MA, the transformation to a multi-user spaceport required implementing methods to foster safe and successful commercial activity while resolving challenges involving: Retirement of the Space Shuttle program; Co-location of multiple NASA programs; Relationships between the NASA programs; Complex relationships between NASA programs and commercial partner operations in exclusive-use facilities; Complex relationships between NASA programs and commercial partner operations in shared-use facilities. NASA KSC S&MA challenges were met with long-term planning and solutions involving cooperation with the Spaceport Integration and Services Directorate. This directorate is responsible for managing active commercial partnerships with customer advocacy and services management, providing a dedicated and consistent level of support to a wide array of commercial operations. This paper explores these solutions, their relevance to the current commercial space industry, and the challenges that continue to drive improvement with a focus on areas of safety management and risk assessment that have been crucial in KSC's evolution into a multi-user spaceport. These solutions may be useful to government entities and private companies looking to partner with the commercial space industry.

Range↗
NASA NTRSDate not supplied

Neuro-Vestibular Examination During and Following Spaceflight (Vestibular Health)

BACKGROUND Adaptation to microgravity during spaceflight causes neurological disturbances that are either directly or indirectly mediated by the vestibular system. These disturbances can include space motion sickness, spatial disorientation, and cognitive impairment, as well as changes in head-eye coordination, vestibulo-ocular reflexes, and control of posture and locomotion. Otolith-mediated reflex gains appear to adapt rapidly during spaceflight and after landing. However, animal studies have shown that structural modifications of the vestibular sensory apparatus develop during long-duration spaceflight. To date, no studies have characterized the severity of vestibular syndromes experienced by astronauts as a function of the duration of spaceflight or whether the effects are caused by changes at the peripheral end organs, midbrain, cerebellum, or vestibular cortex. OBJECTIVES We are investigating temporal vestibular changes in crewmembers of short, 6-month, and one-year missions to identify trends in adaptation of vestibular health and performance in orbit and after landing. We are also differentiating between peripheral and central vestibular forms of vertigo and oculomotor disorders. METHODS Recordings of eye, head, and body movements, as well as subjective reports of perception of motion, are being used to determine the presence of abnormal eye movements, dysmetria, motion sickness symptoms, and illusions of motion during head or body movements. This includes characterization of temporal trends in central compensation for vestibular (otolith) asymmetry. In-flight examinations are being performed early in the mission (Flight Days 1 and 30) and once every 2-3 months thereafter. Postflight examinations are performed after return (R) from the mission on R+0, R+4, R+9, and R+30. The inflight and postflight motion sickness questionnaires are customized to support data sharing across related studies. Ground-based control testing has been performed on healthy volunteers(18 females, 14 males;38.6 ± 9.2 years) in the laboratory to estimate mean normative responses, and on patients with bilateral vestibulopathy (BVP) (17 females, 13 males; 60.6 ± 13.0 years) at the University of Caen. RESULTS As of September 2024, two crewmembers have completed all preflight, inflight, and postflight testing. Additional crewmembers are currently enrolled and data collection is currently ongoing. For ground testing, BVP patients performed similarly to previous postflight astronauts on R+0 in various walking performance tasks. Three additional body movement perception tasks have been tested. For the Triangle Completion Task, BVP patients had a larger mean angle of deviation and longer mean distance than healthy controls. For the Self-Rotation Task and Distance Perception Task, BVP patients had larger errors than healthy controls. These data suggest that vestibular deficiencies impact all aspects of body movement perception tested; whereas previous studies suggest that vestibular deficiencies are only associated with directional errors, not with overall trajectories/path lengths. These data will be compared to those of crewmembers during early postflight readaptation. RELEVANCE If the observed symptoms in crewmembers are more deleterious after the year-long missions than those documented after 6-month missions, then relevant countermeasures will be required to maintain the health and operational performance of astronauts during longer missions. Depending on the etiology of the vestibular syndrome revealed by these tests, countermeasures will be proposed based on vestibular rehabilitation therapies currently used in patients with vestibular disorders, such as habituation, gaze stabilization, and/or balance training exercises. ACKNOWLEDGEMENT This work is supported by NASA’s Human Research Program Human Health Countermeasures Element.

T R Macaulay↗
NASA NTRS2012

Constructing an Efficient Self-Tuning Aircraft Engine Model for Control and Health Management Applications

Self-tuning aircraft engine models can be applied for control and health management applications. The self-tuning feature of these models minimizes the mismatch between any given engine and the underlying engineering model describing an engine family. This paper provides details of the construction of a self-tuning engine model centered on a piecewise linear Kalman filter design. Starting from a nonlinear transient aerothermal model, a piecewise linear representation is first extracted. The linearization procedure creates a database of trim vectors and state-space matrices that are subsequently scheduled for interpolation based on engine operating point. A series of steady-state Kalman gains can next be constructed from a reduced-order form of the piecewise linear model. Reduction of the piecewise linear model to an observable dimension with respect to available sensed engine measurements can be achieved using either a subset or an optimal linear combination of "health" parameters, which describe engine performance. The resulting piecewise linear Kalman filter is then implemented for faster-than-real-time processing of sensed engine measurements, generating outputs appropriate for trending engine performance, estimating both measured and unmeasured parameters for control purposes, and performing on-board gas-path fault diagnostics. Computational efficiency is achieved by designing multidimensional interpolation algorithms that exploit the shared scheduling of multiple trim vectors and system matrices. An example application illustrates the accuracy of a self-tuning piecewise linear Kalman filter model when applied to a nonlinear turbofan engine simulation. Additional discussions focus on the issue of transient response accuracy and the advantages of a piecewise linear Kalman filter in the context of validation and verification. The techniques described provide a framework for constructing efficient self-tuning aircraft engine models from complex nonlinear simulations.Self-tuning aircraft engine models can be applied for control and health management applications. The self-tuning feature of these models minimizes the mismatch between any given engine and the underlying engineering model describing an engine family. This paper provides details of the construction of a self-tuning engine model centered on a piecewise linear Kalman filter design. Starting from a nonlinear transient aerothermal model, a piecewise linear representation is first extracted. The linearization procedure creates a database of trim vectors and state-space matrices that are subsequently scheduled for interpolation based on engine operating point. A series of steady-state Kalman gains can next be constructed from a reduced-order form of the piecewise linear model. Reduction of the piecewise linear model to an observable dimension with respect to available sensed engine measurements can be achieved using either a subset or an optimal linear combination of "health" parameters, which describe engine performance. The resulting piecewise linear Kalman filter is then implemented for faster-than-real-time processing of sensed engine measurements, generating outputs appropriate for trending engine performance, estimating both measured and unmeasured parameters for control purposes, and performing on-board gas-path fault diagnostics. Computational efficiency is achieved by designing multidimensional interpolation algorithms that exploit the shared scheduling of multiple trim vectors and system matrices. An example application illustrates the accuracy of a self-tuning piecewise linear Kalman filter model when applied to a nonlinear turbofan engine simulation. Additional discussions focus on the issue of transient response accuracy and the advantages of a piecewise linear Kalman filter in the context of validation and verification. The techniques described provide a framework for constructing efficient self-tuning aircraft engine models from complex nonlinear simulatns.

Armstrong, Jeffrey B.↗
DOE OSTI2015

Electric Vehicles and the Electric Grid

In response to the need for the decarbonization of the transport sector and to reduce the reliance on fossil fuels, it is expected that large fleets of plug-in electric vehicles (PEVs) will constitute an important share of the electricity demand in the not so distant future. These devices can, and would behave as any regular demand if they are allowed to charge as soon as they are connected to the electric grid. If such charging process is allowed, then several adverse impacts on the power grids such as increased system-wide peak demand, and early reinforcements of the distribution, transmission and/or generation systems would be required. However, as opposed to conventional demands, these new devices are equipped with a battery that enables them deferring their needs for electric energy in time. If the pliant nature of this demand is exploited in such a way that the charging of these devices takes place when it is more convenient for the power system, then not only would the adverse impacts to the system would be avoided, but also, a new stream of services could be offered to the electric power grid in the form of demand response, power injections in V2G and regulating reserves. This article discusses the consequences of integrating significant volumes of PEVs into power systems, in both, uncontrolled and controlled manners.

Ortega Vazquez, Miguel A.↗
DOE OSTI2016

Ba 3 (Cr 0.97(1) Te 0.03(1) ) 2 TeO 9 : in Search of Jahn–Teller Distorted Cr(II) Oxide

A novel 6H - type hexagonal perovskite Ba 3 (Cr 0.97(1) Te 0.03 (1 ) ) 2 TeO 9 was prepared at high pressure (6 GPa) and temperature ( 1 773 K). Both transmission electron microscopy and synchrotron powder x - ray diffraction data demonstrate that Ba 3 (Cr 0.97(1) Te 0.03(1) ) 2 TeO 9 crystallize s in P6 3 / mmc with face - shared (Cr 0.97(1) Te 0.03(1) )O 6 octahedral pairs interconnected with TeO 6 octahedra via corner - sharing. Structure analysis shows a mixed Cr 2+ /Cr 3+ valence state with ~ 10% Cr 2+ . The existence of Cr 2+ in Ba 3 (Cr 2+ 0.10(1) Cr 3+ 0.87(1) Te 6+ 0.03 ) 2 TeO 9 is further evidenced by x - ray absorption near edge spectr oscopy . Magnetic properties measurements show a paramagnetic response down to 4 K and a small glassy - state curvature at low temperature. In this work, the o ctahedral Cr 2+ O 6 component is stabilized in an oxide material for the first time ; the expected Jahn - Teller distortion of high - spin ( d 4 ) Cr 2+ is not found , which is attributed to the small proportion of Cr 2+ (~ 10%) and the face - sharing arrangement of CrO 6 octahedral pairs, that structu rally dis favor axial distortion.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2015

Transmitted virus fitness and host T cell responses collectively define divergent infection outcomes in two HIV-1 recipients

Control of virus replication in HIV-1 infection is critical to delaying disease progression. While cellular immune responses are a key determinant of control, relatively little is known about the contribution of the infecting virus to this process. To gain insight into this interplay between virus and host in viral control, we conducted a detailed analysis of two heterosexual HIV-1 subtype A transmission pairs in which female recipients sharing three HLA class I alleles exhibited contrasting clinical outcomes: R880F controlled virus replication while R463F experienced high viral loads and rapid disease progression. Near full-length single genome amplification defined the infecting transmitted/founder (T/F) virus proteome and subsequent sequence evolution over the first year of infection for both acutely infected recipients. T/F virus replicative capacities were compared in vitro , while the development of the earliest cellular immune response was defined using autologous virus sequence-based peptides. The R880F T/F virus replicated significantly slower in vitro than that transmitted to R463F. While neutralizing antibody responses were similar in both subjects, during acute infection R880F mounted a broad T cell response, the most dominant components of which targeted epitopes from which escape was limited. In contrast, the primary HIV-specific T cell response in R463F was focused on just two epitopes, one of which rapidly escaped. This comprehensive study highlights both the importance of the contribution of the lower replication capacity of the transmitted/founder virus and an associated induction of a broad primary HIV-specific T cell response, which was not undermined by rapid epitope escape, to long-term viral control in HIV-1 infection. It underscores the importance of the earliest CD8 T cell response targeting regions of the virus proteome that cannot mutate without a high fitness cost, further emphasizing the need for vaccines that elicit a breadth of T cell responses to conserved viral epitopes.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2023

Pumping Iron: A Multi-omics Analysis of Two Extremophilic Algae Reveals Iron Economy Management

Marine algae are responsible for half of the world's primary productivity, but this critical carbonsink is often constrained by insufficient iron. One species of marine algae, Dunaliella tertiolecta, isremarkable for its ability to maintain photosynthesis and thrive in low-iron environments. A relatedspecies, Dunaliella salina Bardawil, shares this attribute but is an extremophile found in hypersaline environments. To elucidate how algae manage their iron requirements, we produced highquality genome assemblies and transcriptomes for both species to serve as a foundation for acomparative multi-omics analysis. We identified a host of iron-uptake proteins in both species,including a massive expansion of transferrins and a novel family of siderophore-iron uptakeproteins. Complementing these multiple iron-uptake routes, ferredoxin functions as a large ironreservoir that can be released by induction of flavodoxin. Proteomic analysis revealed reducedinvestment in the photosynthetic apparatus coupled with remodeling of antenna proteins bydramatic iron-deficiency induction of TIDI1, a light harvesting complex protein found also in otherchlorophytes. These combinatorial iron scavenging and sparing strategies make Dunaliellaunique among photosynthetic organisms

iron homeostasis, phytoplankton, Iron starvation i↗
DOE OSTI2012

Structures of the autoproteolytic domain from the Saccharomyces cerevisiae nuclear pore complex component, Nup145

Nuclear pore complexes (NPCs) are large, octagonally symmetric dynamic macromolecular assemblies responsible for exchange of proteins and RNAs between the nucleus and cytoplasm. NPCs are made up of at least 456 polypeptides from {approx}30 distinct nucleoporins. Several of these components, sharing similar structural motifs, form stable subcomplexes that form a coaxial structure containing two outer rings (the nuclear and cytoplasmic rings), two inner rings, and a membrane ring. The yeast (Saccharomyces cerevisiae) Nup145 and its human counterpart are unique among the nucleoporins, in that they undergo autoproteolysis to generate functionally distinct proteins. The human counterpart of Nup145 is expressed as two alternatively spliced mRNA transcripts. The larger 190 kDa precursor undergoes post-translational autoproteolysis at the Phe863-Ser864 peptide bond yielding the 92 kDa Nup98 and the 96 kDa Nup96. The smaller 98 kDa precursor is also autoproteolysed at an analogous site giving 92 kDa Nup98-N and a 6 kDa C-terminal fragment, which may form a noncovalent complex. The yeast Nup145 precursor [Fig. 1(A)] contains twelve repeats of a 'GLFG' peptide motif (FG repeats) at its N-terminus, an internal autoproteolytic domain (a region of high conservation with the homologous yeast nucleoporins Nup110 and Nup116, neither of which undergo autoproteolysis), followed by the C-terminal domain. Various forms of the FG repeats are present in nearly half of all nucleoporins; they form intrinsically disordered regions implicated in gating mechanisms that control passage of macromolecules through NPCs. Nup145 undergoes autoproteolysis at the Phe605-Ser606 peptide bond to generate two functionally distinct proteins, Nup145N and Nup145C. Subsequently, Nup145C associates with six other proteins to form the heptameric Y-complex, a component of the outer rings of the NPC. Nup145N, on the other hand, can shuttle between the NPC and the nuclear interior. It has been suggested that Nup145N, by analogy with Nup98, carries RNA between the nucleus and the NPC. Nup145 belongs to a highly conserved family of homologs found throughout eukarya. Curiously, the Phe-Ser autoproteolytic site is not always conserved, resulting in the absence of autoproteolysis for some of these closely related proteins. Our structural understanding of NPC function has benefited recently from X-ray crystal structures of segments of individual proteins. As a part of ongoing efforts at the New York SGX Research Center for Structural Genomics (www.nysgxrc.org) to determine crystal structures of distinct components of the yeast NPC, we report herein structures of Nup145N residues 443-605 [Nup145N(443-605)] from the larger autoproteolytic segment. The monomeric architecture of Nup145N(443-605) is similar to that of the autoproteolytic domain of human Nup98-N and the homologous domain of Nup116. In contrast, Nup145N(443-605) and Nup98-N show different modes of association in the crystalline state. Results of Small Angle X-ray Scattering (SAXS) in solution are consistent with the head-to-tail dimer of Nup145N(443-605), observed in two different crystal forms.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2013

Editorial: A Note on Good Research Practice

Good scientific practice and research misconduct have been concerns of mine for more than a decade (Dooley and Kerch, 2000) and in my role as an editor of the International Journal of Greenhouse Gas Control, I feel it is time to speak up and at the very least share my concerns and suggestions as they relate to the integrity of the research published in this journal. Rather than wait to write an editorial on good research practices in response to a major incident, I thought it might be best to be proactive and address some of the trends we see in submissions to this peer reviewed journal and to offer some suggestions for improvement improving the level of scholarship in some – but by no means all – of the papers submitted.

plagerism↗