National Institute For Standards And Technology Research Articles

Abstract 7024: Development of quality control methods for reliable NGS measurement of methylation in cfDNA

Abstract Background and Purpose: Reliable measurement of circulating free genomic DNA (cfDNA) methylation patterns promises a means for cancer early detection as well as treatment response. Use of Next Generation Sequencing (NGS) methods to measure the cfDNA methylome across a large number of potentially methylated CpG sites may enable earlier detection by overcoming stochastic sampling associated with the small specimens obtainable by a blood draw. Wide-spread adoption of these methods for clinical diagnostic applications will be facilitated through improved quality controls that increase reliability. The goal of this study is to assess the performance of the SNAQ-SEQ™ method as a means to establish a limit of detection (LOD) for measurement of methylation at each targeted CpG site. For this purpose, we used test materials that were developed by the National Institute for Standards and Technology (NIST) to mimic methylated cfDNA. Methods: NIST test materials were formulated by physically shearing cell line gDNA then subjecting it to size separation to mimic a size distribution similar to that observed in cfDNA, then mixing sheared DNA in its “native” state of methylation with sheared DNA that was in vitro methylated. Non-sheared NIST test materials also were assessed in these studies. Synthetic spike-in internal standards (IS) were combined with NIST test materials and the combined samples were bisulfite converted, then subjected to PCR-amplicon library preparation. Libraries were sequenced on an Illumina MiSeq instrument and bioinformatic analysis was conducted using the Qiagen CLC Workbench. Results and Conclusions: In initial testing of an off-the-shelf IS for a region of the SOX2 gene, average methylation (preserved C) across 14 targeted CpG sites was 16.4% (0.5%-50%) in the “native” NIST non-sheared sample. This was consistent with the 11.6% methylation across all of SOX2 measured by the NIST. In contrast, in IS corresponding to the targeted SOX2 region the average preserved C was 0.32% (0.03%-0.5%). Use of synthetic internal standards enabled determination of LOD for each individual methylated site, controlling for all known sources of technical error, including inefficient bisulfite conversion, nucleotide substitution error, and alignment error. Studies are now underway that use the NIST test materials to measure methylation at five targets known to be altered in cfDNA from lung cancer subjects, SOX2, CDO1, TAC1, SOX17, and HOXA7. Citation Format: James C. Willey, Erin L. Crawford, Daniel J. Craig, Thomas M. Morrison, Hua-Jun He, James G. Herman. Development of quality control methods for reliable NGS measurement of methylation in cfDNA [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7024.

Secure post‐quantum group key exchange: Implementing a solution based on Kyber

AbstractQuantum computing poses fascinating challenges for current cryptography, threatening the security of many schemes and protocols widely used today. To adapt to this reality, the U.S. National Institute for Standards and Technology (NIST) is currently running a standardization process in search of post‐quantum (classical, yet resistant to quantum attacks) cryptographic tools, focusing on signature schemes and key encapsulation mechanisms. Many of the competing proposals also include designs for two‐party key exchange, which can be combined in different ways to fit scenarios involving parties, that is, yielding group key exchange protocols. However, very few implementations of such group protocols are available to practitioners, which face a non‐trivial challenge when deciding how to implement a protocol for establishing secure group sessions in this new post‐quantum scenario. With this in mind, the authors report on the implementation of a secure post‐quantum group key exchange protocol in the so‐called Quantum Random Oracle Model. The protocol decided to implement is based on a KEM called Kyber, which is one of the finalists of the NIST competition. Not only this group construction is the only one available in the literature using a NIST finalist, but also, among all post‐quantum designs the authors are aware of, it uses this strongest security model (as, e.g. in other proposals, the adversarial interaction with the hash functions of the system is assumed to be exclusively classical). Furthermore, experimental evidence is provided supporting this choice in terms of performance, even if the number of involved entities is large (up to 2000). All data and code are publicly available.

Final report, ongoing key comparison BIPM.QM-K1, ozone at ambient level, comparison with NIST, July 2022

Main textAs part of the ongoing key comparison BIPM.QM-K1, a comparison has been performed between the ozone national standard of the United States maintained by the National Institute for Standards and Technology (NIST) and the common reference standard of the key comparison, maintained by the Bureau International des Poids et Mesures (BIPM). The instruments have been compared over a nominal ozone amount fraction range of 0 nmol mol−1 to 500 nmol mol−1.To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database https://www.bipm.org/kcdb/.The final report has been peer-reviewed and approved for publication by the CCQM, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).

A System-on-a-Chip Implementation of a Post-Quantum Cryptography Scheme for Smart Meter Data Communications.

The security of Smart Meter (SM) systems will be a challenge in the era of quantum computing because a quantum computer might exploit characteristics of well-established cryptographic schemes to reach a successful security breach. From a practical perspective, this paper focuses on the feasibility of implementing a quantum-secure lattice-based key encapsulation mechanism in a SM, hardware-constrained equipment. In this regard, the post-quantum cryptography (PQC) scheme, FrodoKEM, an alternate candidate for the National Institute for Standards and Technology (NIST) post-quantum standardization process, is implemented using a System-on-a-Chip (SoC) device in which the Field Programmable Gate Array (FPGA) component is exploited to accelerate the most time-consuming routines in this scheme. Experimental results show that the execution time to run the FrodoKEM scheme in an SoC device reduces to one-third of that obtained by the benchmark implementation (i.e., the software implementation). Also, the attained execution time and hardware resource usage of this SoC-based implementation of the FrodoKEM scheme show that lattice-based cryptography may fit into SM equipment.

A Sponge-Based Key Expansion Scheme for Modern Block Ciphers

Many systems in use today require strong cryptographic primitives to ensure confidentiality and integrity of data. This is especially true for energy systems, such as smart grids, as their proper operation is crucial for the existence of a functioning society. Because of this, we observe new developments in the field of cryptography every year. Among the developed primitives, one of the most important and widely used are iterated block ciphers. From AES (Advanced Encryption Standard) to LEA (Lightweight Encryption Algorithm), these ciphers are omnipresent in our world. While security of the encryption process of these ciphers is often meticulously tested and verified, an important part of them is neglected—the key expansion. Many modern ciphers use key expansion algorithms which produce reversible sub-key sequences. This means that, if the attacker finds out a large-enough part of this sequence, he/she will be able to either calculate the rest of the sequence, or even the original key. This could completely compromise the cipher. This is especially concerning due to research done into side-channel attacks, which attempt to leak secret information from memory. In this paper, we propose a novel scheme which can be used to create key expansion algorithms for modern ciphers. We define two important properties that a sequence produced by such algorithm should have and ensure that our construction fulfills them, based on the research on hashing functions. In order to explain the scheme, we describe an example algorithm constructed this way, as well as a cipher called IJON which utilizes it. In addition to this, we provide results of statistical tests which show the unpredictability of the sub-key sequence produced this way. The tests were performed using a test suite standardized by NIST (National Institute for Standards and Technology). The methodology of our tests is also explained. Finally, the reference implementation of the IJON cipher is published, ready to be used in software. Based on the results of tests, we conclude that, while more research and more testing of the algorithm is advised, the proposed key expansion scheme provides a very good generation of unpredictable bits and could possibly be used in practice.

The development of natural gas and hydrogen pipeline capital cost estimating equations

Natural gas pipeline cost data collected by the Oil and Gas Journal (O&GJ) [1] for interstate pipelines constructed from 1980 through 2017 were used to develop capital cost estimating equations that are a function of pipeline diameter, length, and U.S. region. Equations were developed for material, labor, miscellaneous, and right-of-way costs, the four cost components in the O&GJ data, for six different regions of the United States (U.S.). Each equation is a function of pipeline diameter and length.Adjustment mechanisms were then developed for converting the natural gas pipeline equations into equations for estimating the costs of hydrogen pipelines. These adjustments were based in part on an analysis completed by the National Institute for Standards and Technology (NIST) [2,3]. The results of this work were used to update cost models in the Hydrogen Delivery Scenario Analysis Model (HDSAM) [4], developed by Argonne National Laboratory for the U.S. Department of Energy's Hydrogen Program. Our analysis shows a wide range of pipeline cost across different U.S. regions, especially with respect to labor and right-of-way costs. The developed cost formulas for hydrogen pipelines are both important and timely as hydrogen is being considered as a zero-carbon energy carrier with the potential to decarbonize all energy sectors, and the cost of hydrogen transportation is essential for techno-economic analysis of its potential use in these sectors.

Efficient Error Detection Architectures for Postquantum Signature Falcon’s Sampler and KEM SABER

Among the National Institute for Standards and Technology (NIST) postquantum cryptography (PQC) standardization Round 3 finalists (announced in 2020 and anticipated to conclude in 2022–2024), SABER and Falcon are efficient key encapsulation mechanism (KEM) and compact signature scheme, respectively. SABER is a simple and flexible cryptographic scheme, highly suitable for thwarting potential attacks in the postquantum era. Implementing SABER can be performed solely in hardware (HW) or on HW/software coprocessors. On the other hand, the compact key size, efficient design, and strong reliability proof in the quantum random oracle model (QROM) make Falcon a highly suitable signature algorithm for PQC. Although Falcon is crucial as a PQC signature scheme, the utilization of the Gaussian sampler makes it vulnerable to malicious attacks, e.g., fault attacks. This is the first work to present error detection schemes embedded efficiently in SABER as well as Falcon’s sampler architectures, which can detect both transient and permanent faults. Moreover, we implement HW design for the ModFalcon signature algorithm as well as the Gaussian sampler. These schemes are implemented on a formerly Xilinx field-programmable gate array (FPGA) family, for both SABER and Falcon variants, where we assess the error coverage and the performance. The proposed schemes incur low overhead (the area, delay, and power overheads being 22.59%, 19.77%, and 10.67%, respectively, in the worst case) while providing a high fault detection rate (99.9975% in the worst case scenario), making them suitable for high efficiency and compact HW implementations of constrained applications.

Assessment of human nuclear and mitochondrial DNA qPCR assays for quantification accuracy utilizing NIST SRM 2372a

In forensic DNA casework, a highly accurate real-time quantitative polymerase chain reaction (qPCR) assay is recommended per the Scientific Working Group on DNA Analysis Methods (SWGDAM) (SWGDAM Validation Guidelines for DNA Analysis Methods [1]) to determine whether a DNA sample is of sufficient quantity and robust quality to move forward with downstream short tandem repeats (STR) or sequencing analyses. Most of these assays rely on a standard curve, referred to herein and traditionally as absolute qPCR, in which an unknown is compared, relative to that curve. However, one fundamental issue with absolute qPCR is the quantifiable concentration of commercial assay standards can vary depending on (1) origin, i.e., whether from a cell line or a human subject, (2) supplier, (3) lot number, (4) shipping method, etc. In 2018, the National Institute for Standards and Technology (NIST) released a human DNA standard reference material for evaluating qPCR quantification standards, Standard Reference Material (SRM) 2372a, Romsos et al. (2018) [2] which contains three well-characterized human genomic DNA samples: Component A) a single male1 donor, Component B) a single female1 donor, and Component C) a 1:3 male2:female2 donor, each with certification data for nDNA and informational mitochondrial DNA(mtDNA)/nuclear DNA (nDNA) ratio data. The SRM 2372a was used to assess four qPCR assays: (1) Quantifiler Trio (Thermo Fisher Scientific, Waltham, MA) for nDNA quantification, (2) NovaQUANT (EMD Millipore Corporation, San Diego, CA) for nDNA and mtDNA quantification, (3) a custom duplex mtDNA assay, and (4) a custom triplex mtDNA assay. Additionally, extracts from eighteen (18) skeletal remains were tested with the latter three assays for concordance of DNA concentration and with assays (2) and (3), for the degradation state. Our assessment revealed that an accurate, efficient, and reproducible qPCR assay is dependent on (1) the quality and reliability of the DNA standard, (2) the qPCR chemistry, and (3) the specific primers, and probes (if applicable), used in an assay. Our findings indicate qPCR assays may not always quantify as expected and that performance of each lot should be verified using a well-characterized DNA standard such as the NIST SRM 2372a and adjusted if warranted.

Multi attribute method implementation using a High Resolution Mass Spectrometry platform: From sample preparation to batch analysis.

Quality control of biopharmaceuticals such as monoclonal antibodies (mAbs) has been evolving and becoming more challenging as the requirements of the regulatory agencies increase due to the demanding complexity of products under evaluation. Mass Spectrometry (MS)-based methods such as the multi-attribute method (MAM) are being explored to achieve a deeper understanding of the attributes critical for the safety, efficacy, and quality of these products. MAM uses high mass accuracy/high-resolution MS data that enables the direct and simultaneous monitoring of relevant product quality attributes (PQAs, in particular, chemical modifications) in a single workflow, replacing several orthogonal methods, reducing time and costs associated with these assays. Here we describe a MAM implementation process using a QTOF high resolution platform. Method implementation was accomplished using NIST (National Institute for Standards and Technology) mAb reference material and an in-process mAb sample. PQAs as glycosylation profiles, methionine oxidation, tryptophan dioxidation, asparagine deamidation, pyro-Glu at N-terminal and glycation were monitored. Focusing on applications that require batch analysis and high-throughput, sample preparation and LC-MS parameters troubleshooting are discussed. This MAM workflow was successfully explored as reference analytical tool for comprehensive characterization of a downstream processing (DSP) polishing platform and for a comparability study following technology transfer between different laboratories.

Preface

Julian Gröbner, Guest editor and chairman of the NEWRAD scientific committee Physikalisch-Meteorologisches Observatorium Davos, World Radiation Center (PMOD/WRC)Dorfstrasse 337260 Davos Dorf, SwitzerlandThe 14th International Conference on New Developments and Applications in Optical Radiometry (NEWRAD 2021) was organised by the National Institute for Standards and Technology (NIST), Boulder, United States and held online from 21 to 24 June 2021. Due to the COVID pandemic the original venue at Boulder in June 2020 had to be postponed and changed to a virtual event with a novel schedule consisting of pre-recorded talks and live sessions with the presenters to interact with conference attendees. The event was very well attended, notwithstanding the global participation with corresponding challenging time zones of the participants. A total of 274 registrations were received, with typically more than 100 attendees joining the online sessions. The NEWRAD scientific Committee would like to thank John Lehman and the whole local organising team for organising and holding this excellent event in the frame of these challenging conditions. 142 presentations were submitted, of which 48 were selected for oral talks, while the remaining submissions were presented as posters.Julian Gröbner, Guest editor and chairman of the NEWRAD scientific committee this title available in this pdf.

Design for a portable calibration system for the Full-sun UV Rocket SpecTrometer instrument

The Full-sun Ultraviolet Rocket SpecTrograph (FURST) is a sounding rocket designed to acquire the first full-disk integrated high resolution vacuum ultraviolet (VUV) spectra of the Sun. The data enable analysis of the Sun comparable to stellar spectra measured by astronomical instruments such as those on board the Hubble Space Telescope. The mission is jointly operated by teams at Montana State University (MSU), developing the instrument, and Marshall Space Flight Center (MSFC), developing the camera and calibration systems, and is scheduled to launch from White Sands Missile Range, New Mexico, in 2022. This mission requires the development of a pre- and post-launch calibration plan for absolute radiometric and wavelength calibration to reliably generate Hubble analogue spectra. Absolute radiometric calibration, though initially planned to be performed at the National Institute for Standards and Technology (NIST) calibration facilities, is now planned to be completed with a portable VUV calibration system provided by MSFC, due to instrument incompatibilities with NIST infrastructure. The portable calibration system is developed to provide absolute wavelength calibration and track changes in calibration over the duration of the mission. The portable calibration system is composed mainly of a VUV collimator equipped with an extreme ultraviolet line source and calibrated photodiodes. The calibration system is developed to accommodate both repeatable wavelength and radiometric testing of the FURST instrument at various test sites before and after launch. Presented here are the requirements, design, and implementation of this portable calibration system with a focus on those features most significant to radiometric measurements.

SI-traceable Spectral Irradiance Radiometric Characterization and Absolute Calibration of the TSIS-1 Spectral Irradiance Monitor (SIM)

The current implementation for continuous, long-term solar spectral irradiance (SSI) monitoring is the Total and Spectral Solar Irradiance Sensor (TSIS-1) Spectral Irradiance Monitor (SIM) that began operations from the International Space Station (ISS) in March 2018 and nominally provides an SSI spectrum every 12 h. Advances in both instrument design and spectral irradiance calibration techniques have resulted in the TSIS-1 SIM achieving higher absolute accuracy than its predecessor instrument in the wavelength range (200–2400 nm). A comprehensive detector-based Spectral Radiometer Facility (SRF) was developed in collaboration with the US National Institute for Standards and Technology (NIST) to ensure the ties to spectral SI standards in power and irradiance. Traceability is achieved via direct laser calibration of a focal plane electrical substitution radiometer (ESR) against a cryogenic radiometer in power and also irradiance responsivity via calibrated apertures. The SIM accuracy definition followed an absolute sensor approach based on a full radiometric measurement equation where component-level performance characterizations and calibrations were quantified with an associated uncertainty error budget and verified by independent measurements for each parameter. Unit-level characterizations were completed over the full operational envelope of external driving factors (e.g., pointing and temperature ranges) and were allowed for the independent parameterization of sub-assembly performance for expected operating conditions. Validation and final instrument end-to-end absolute calibration in the Laboratory for Atmospheric and Space Physics (LASP)-SRF achieved low combined standard uncertainty (uc < 0.25%, k = 1) in spectral irradiance.

Integrating cost–benefit analysis into the NIST Cybersecurity Framework via the Gordon–Loeb Model

Abstract The National Institute for Standards and Technology (NIST) Cybersecurity Framework has rapidly become a widely accepted approach to facilitating cybersecurity risk management within organizations. An insightful aspect of the NIST Cybersecurity Framework is its explicit recognition that the activities associated with managing cybersecurity risk are organization specific. The NIST Framework also recognizes that organizations should evaluate their cybersecurity risk management on a cost–benefit basis. The NIST Framework, however, does not provide guidance on how to carry out such a cost–benefit analysis. This article provides an approach for integrating cost–benefit analysis into the NIST Cybersecurity Framework. The Gordon–Loeb (GL) Model for cybersecurity investments is proposed as a basis for deriving a cost-effective level of spending on cybersecurity activities and for selecting the appropriate NIST Implementation Tier level. The analysis shows that the GL Model provides a logical approach to use when considering the cost–benefit aspects of cybersecurity investments during an organization’s process of selecting the most appropriate NIST Implementation Tier level. In addition, the cost–benefit approach provided in this article helps to identify conditions under which there is an incentive to move to a higher NIST Implementation Tier.

Determination of Minerals and Trace Elements in Milk, Milk Products, Infant Formula, and Adult Nutrition: Collaborative Study 2011.14 Method Modification

Abstract Official Method SM 2011.14/ISO 15151:2018/IDF 229:2018 uses microwave digestion of samples and inductively coupled plasma–atomic emission spectrometry for determination of nine elements, including Ca, Cu, Fe, K, Mg, Mn, Na, P, and Zn. The method was evaluated in a collaborative study of 25 products, including 13 fortified nutritional products (powders, ready-to-feed liquids, and liquid concentrates), five product placebos, six dairy products (liquids, powders, butter, and processed cheese), and the National Institute for Standards and Technology (NIST) Standard Reference Material (SRM) 1849a, in compliance with AOAC INTERNATIONAL Standard Method Performance Requirement (SMPR®) 2014.004. This study significantly expanded the applicability of Official Method 2011.14 beyond the original scope of chocolate milk powder, dietetic milk powder, infant cereal, peanut butter, and wheat gluten. The study included 14 collaborators from 11 countries, and results were compared to SMPR 2014.004. Accuracy of the method was demonstrated using NIST SRM 1849a, yielding recoveries across all laboratories of 98–101% for the nine elements. Precision for the 13 fortified nutritional product samples was 2.2–3.9% for repeatability (relative SD of repeatability) and 6.0–12.2% for reproducibility (RSDR). Excluding Mn, which was present at a wide range of concentrations, the reproducibility was 6.0–9.5%, meeting the performance requirements of SMPR 2014.004. Placebo samples (not fortified with Cu, Fe, Mn, or Zn) yielded acceptable repeatability of 1.8–2.9% for Ca, K, Mg, Na, and P (minerals) but 5.4–29.4% for the low levels of Cu, Fe, Mn, and Zn (trace elements). Reproducibility for the placebos showed the same pattern, with acceptable reproducibility (5.4–10.3%) for minerals but not for the low levels of the trace elements (13.2–82.8%). In the six dairy product samples, repeatability ranged from 1.6 to 3.6% for the minerals, Zn, and the low range of Mn but from 9.4 to 24.6% for Cu, Fe, and the high range of Mn, where concentrations were low as for the nutritional placebos. Reproducibility in the dairy samples was 5.3–8.8% for the minerals but 11.4–55.0% for the trace elements. The mean concentrations of Cu, Fe, and Zn in the dairy products were similar with those in the placebo products, while Zn was present at levels more similar with the fortified nutritional products. Thus, the method met the SMPR criteria except where the trace minerals were present at very low levels. Based on these results, the AOAC Stakeholder Panel for Infant Formula and Adult Nutritionals recommended Final Action status of the expanded applicability of the method. The method was adopted as Final Action by the AOAC Official Methods Board.

Simple and accurate candidate reference measurement procedure for total testosterone in human serum by one-step liquid-liquid extraction coupled with isotope dilution mass spectrometry.

Testosterone in human serum is commonly tested in clinical laboratories using immunoassay methods as well as liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods. To standardize and ensure the accuracy of the measurement results, reference procedures with higher metrological order are required. A simple measurement procedure based on one-step liquid-liquid extraction (LLE) and liquid chromatography-isotope dilution tandem mass spectrometry (LC-IDMS/MS) was developed for total testosterone in human serum. The procedure involved serum spiked with 13C3-testosterone, equilibration for 2h, and extraction with an organic solvent. Testosterone certified reference material (CRM) was used as the calibration standard to ensure the traceability to the International System of Units (SI). Testosterone in serum CRMs from the National Institute for Standards and Technology (NIST) and LGC were used to validate the accuracy of the newly developed method. The deviations of the obtained values from the NIST and LGC certified values ranged from -0.55% to 0.45%. Similarly, the coefficient of variations (CVs) of the replicate measurements were in the range of 0.55% and 0.78%, respectively. The relative expanded uncertainties were comparable with those of the certified materials. The newly developed LC-IDMS/MS procedure demonstrated adequate trueness and precision, and was simple to perform. The method can be used for value assignment of testosterone in external quality assessment (EQA) materials as well as certification of CRMs in the future. Graphical abstract.

Data‐driven glass/ceramic science research: Insights from the glass and ceramic and data science/informatics communities

AbstractData‐driven science and technology have helped achieve meaningful technological advancements in areas such as materials/drug discovery and health care, but efforts to apply high‐end data science algorithms to the areas of glass and ceramics are still limited. Many glass and ceramic researchers are interested in enhancing their work by using more data and data analytics to develop better functional materials more efficiently. Simultaneously, the data science community is looking for a way to access materials data resources to test and validate their advanced computational learning algorithms. To address this issue, The American Ceramic Society (ACerS) convened a Glass and Ceramic Data Science Workshop in February 2018, sponsored by the National Institute for Standards and Technology (NIST) Advanced Manufacturing Technologies (AMTech) program. The workshop brought together a select group of leaders in the data science, informatics, and glass and ceramics communities, ACerS, and Nexight Group to identify the greatest opportunities and mechanisms for facilitating increased collaboration and coordination between these communities. This article summarizes workshop discussions about the current challenges that limit interactions and collaboration between the glass and ceramic and data science communities, opportunities for a coordinated approach that leverages existing knowledge in both communities, and a clear path toward the enhanced use of data science technologies for functional glass and ceramic research and development.

Determination of Minerals and Trace Elements in Milk, Milk Products, Infant Formula, and Adult Nutrition: Collaborative Study 2011.14 Method Modification

Official MethodSM 2011.14/ISO 15151:2018/IDF 229:2018 uses microwave digestion of samples and inductively coupled plasma-atomic emission spectrometry for determination of nine elements, including Ca, Cu, Fe, K, Mg, Mn, Na, P, and Zn. The method was evaluated in a collaborative study of 25 products, including 13 fortified nutritional products (powders, ready-to-feed liquids, and liquid concentrates), five product placebos, six dairy products (liquids, powders, butter, and processed cheese), and the National Institute for Standards and Technology (NIST) Standard Reference Material (SRM) 1849a, in compliance with AOAC INTERNATIONAL Standard Method Performance Requirement (SMPR®) 2014.004. This study significantly expanded the applicability of Official Method 2011.14 beyond the original scope of chocolate milk powder, dietetic milk powder, infant cereal, peanut butter, and wheat gluten. The study included 14 collaborators from 11 countries, and results were compared to SMPR 2014.004. Accuracy of the method was demonstrated using NIST SRM 1849a, yielding recoveries across all laboratories of 98-101% for the nine elements. Precision for the 13 fortified nutritional product samples was 2.2-3.9% for repeatability (relative SD of repeatability) and 6.0-12.2% for reproducibility (RSDR). Excluding Mn, which was present at a wide range of concentrations, the reproducibility was 6.0-9.5%, meeting the performance requirements of SMPR 2014.004. Placebo samples (not fortified with Cu, Fe, Mn, or Zn) yielded acceptable repeatability of 1.8-2.9% for Ca, K, Mg, Na, and P (minerals) but 5.4-29.4% for the low levels of Cu, Fe, Mn, and Zn (trace elements). Reproducibility for the placebos showed the same pattern, with acceptable reproducibility (5.4-10.3%) for minerals but not for the low levels of the trace elements (13.2-82.8%). In the six dairy product samples, repeatability ranged from 1.6 to 3.6% for the minerals, Zn, and the low range of Mn but from 9.4 to 24.6% for Cu, Fe, and the high range of Mn, where concentrations were low as for the nutritional placebos. Reproducibility in the dairy samples was 5.3-8.8% for the minerals but 11.4-55.0% for the trace elements. The mean concentrations of Cu, Fe, and Zn in the dairy products were similar with those in the placebo products, while Zn was present at levels more similar with the fortified nutritional products. Thus, the method met the SMPR criteria except where the trace minerals were present at very low levels. Based on these results, the AOAC Stakeholder Panel for Infant Formula and Adult Nutritionals recommended Final Action status of the expanded applicability of the method. The method was adopted as Final Action by the AOAC Official Methods Board.

Real-time interferometric quantum random number generation on chip

We demonstrate on-chip quantum random number generation at high data rates using the random phases of gain-switched laser pulses. Interference of the gain-switched pulses produced by two independent semiconductor lasers is performed on a photonic integrated circuit (PIC) and the resulting pulse train is received and processed in real-time using homebuilt capture electronics consisting a field programmable gate array (FPGA) and a 10-bit digitizer. Random numbers with low correlation coefficient are shown for pulse clock rates of 1 GHz and data rates of 8 Gbps. The random numbers are also shown to successfully pass all tests within the National Institute for Standards and Technology (NIST) test suite. The system provides genuine random numbers in a compact platform that can be readily integrated into existing quantum cryptographic technology.

Estimating uncertainty of target values for DEQAS serum materials

The External Quality Assessment (EQA) scheme for vitamin D metabolites (DEQAS) distributes human serum samples to laboratories across the world to assess their performance in measuring serum total 25-hydroxyvitamin D [25(OH)D], i.e. the sum of the concentrations of serum 25(OH)D2 and 25(OH)D3. In 2013 DEQAS, in collaboration with the Vitamin D Standardization Program (VDSP), became an accuracy-based EQAS when the National Institute for Standards and Technology (NIST) began assigning 25(OH)D target values to DEQAS serum samples using their Joint Committee for Traceability in Laboratory Medicine (JCTLM) approved reference measurement procedure (RMP). Historically, NIST has performed 4 determinations of 25-OHD2 and 25-OHD3 on each sample and used the mean values to calculate a single ‘target value’ for Total 25-OHD against which performance was judged. By definition the target values cannot be exact and each is associated with a level of uncertainty. The total uncertainty (UNIST) has two components, one from the 25(OH)D2, and 25(OH)D3 measurements and the other associated with the calibration procedure. The total combined uncertainty is calculated by adding up these uncertainties. In future, uncertainties will be attached to the target value in each DEQAS serum sample, starting with the next distribution cycle in 2019. Confidence intervals obtained using these uncertainties will allow DEQAS participants to determine if their result agrees with the NIST assigned target value. Furthermore, if the value falls within the confidence interval the laboratory’s assay would be regarded as traceable, i.e. standardized, to the NIST RMP.

The Economic Impacts of the Advanced Encryption Standard, 1996–2017

This paper evaluates the net social benefits of advanced encryption standards (AES), which is one of many areas where the National Institute for Standards and Technology (NIST) has promoted innovation and industrial competitiveness to ensure that public and private computer systems can protect the confidentiality, availability, and integrity of digital information in the face of ever more powerful computers and developments in the field of cryptography.