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The Quarterly Magazine of NIST’s Material Measurement 

SUMMER 2016

MATERIAL MATTERS

Shape-Changing Enzyme Suggests 

How Small Doses of Anti-HIV Drug 

Might Treat Alzheimer’s Disease
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TABLE OF CONTENTS

A Message from the MML Director 3

Shape-Changing Enzyme Suggests How Small Doses of Anti-HIV Drug Might Treat Alzheimer’s Disease 4

New Model May Help Solve the Mystery of How Lithium Stabilizes Moods 5

A Call for Developing—and Using—Consensus Standards to Ensure the Quality of Cell Lines 6 

NIST and Stanford Launch Long-Term Measurement Initiative to Boost the U.S. Bio-Economy 7

An Extraordinary Standard: New NIST Protein Could Spur Biopharmaceutical Innovation 8

NIST Forensic Scientist Helps Vietnamese Counterparts Identify Wartime Remains 10

A Crack in the Mystery of ‘Oobleck’—Friction Thickens Fluids 11

How Do Nature’s Materials Stack Up? “Patchy” Framework Offers New Insights into Self-Assembly 12

Simpler, Faster, and Cheaper: A Full-filling Approach to Making Carbon Nanotubes of Consistent Quality 13

Outreach and Partnering 16

Awards 17

NIST Standard Story 18

Publications 19

CONTRIBUTORS

Editor | Torey Liepa

Contributors | Leah Kauffman | Mark Bello | Rich Press

Cover Image | Kyle Anderson/NIST

Contact MML | mmlinfo@nist.gov
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A MESSAGE FROM THE MML DIRECTOR

The chemical industry, which accounts for more than 25% of the U.S. gross domestic 

product, relies heavily upon catalysts, substances that speed the rate of chemical reactions. 

Without catalysts, most chemical reactions happen so slowly or at such high temperatures 

and pressures that the resulting products wouldn’t be profitable. Ninety percent of all 

chemical products are made with catalysts.

Small improvements in the efficiency of a catalyst can result in significant savings in the 

use of energy, feedstock material, and water, and so yield a competitive advantage and 

higher profits, and potentially lead to lower prices for consumers and more jobs. In addition 

to seeking higher rates of efficiency, the chemical industry is looking for new catalysts 

that minimize the environmental impact of industrial processes and reduce emissions of 

greenhouse gases to meet regulations in U.S. and global markets. 

MML’s experts in the chemical sciences and engineering have been talking with industry 

members about these issues and will soon do what NIST does best: convene stakeholders to 

understand their measurement needs so we can meet them with solutions that will benefit the 

entire industry. That workshop is scheduled to take place in fall 2016. We already know that 

the chemical industry needs better data on the mechanisms of reactions as they happen in 

real working conditions so they can build accurate, reliable, and fast models of new catalysts 

before undertaking large-scale, costly trials of new catalysts on their production floors. This 

goal will require an industry-wide effort to attain and share fundamental knowledge of 

complex reactions, which MML has the knowledge and experience to help lead.

Better simulations of potential catalysts will also need catalyst reference materials, physical 

artifacts that have been intensively characterized under controlled conditions with 

documented methods and validated data, more realms in which MML staff members, who 

oversee the NIST-wide Standard Reference Material program, are experts. These reference 

materials will allow researchers in the chemical industry to validate their own measurements 

and help ensure the reliability of their data.

The transfer of technical expertise from a lab like MML to industry is, ideally, an ongoing 

process that doesn’t end with the sale of a reference material. To keep the knowledge 

exchange going, we’re forming an alliance with several universities in the region to provide 

measurement services and data to the chemical industry. University students will have the 

opportunity to train at NIST while working on industry’s top problems, and mingle with 

industry chemical engineers working in NIST labs to perfect new measurement science, a 

continual exchange of ideas that results in more American innovation. 

Laurie Locascio, Ph.D.

Director

Material Measurement 

Laboratory

NIST
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SHAPE-CHANGING ENZYME SUGGESTS HOW SMALL DOSES OF ANTI-HIV DRUG MIGHT 

TREAT ALZHEIMER’S DISEASE

For a promising pathway to treating 

Alzheimer’s patients, “aim here.” 

That’s what NIST researchers advised 

collaborators hunting for molecules 

that, by linking to a normally occurring 

enzyme, rev up the brain’s capacity for 

clearing cholesterol—a boost associated 

with improvements in memory and other 

benefits in animal studies.

The target pinpointed by the NIST 

scientists is where an approved anti-HIV 

drug—efavirenz—latches to the enzyme 

already responsible for about 80 percent 

of the cholesterol elimination from the 

human brain. Obtained with a cuttingedge atom-substitution technology called 

hydrogen-deuterium exchange (HDX), 

the molecular roadmap shows how small 

amounts of the drug can kick the enzyme, 

called CYP46A1, into higher gear.

With this information, a team led 

by Irina Pikuleva of Case Western 

Reserve University now has the full 

story behind the drug’s mechanism of 

action, key evidence in their proposal 

to launch clinical trials of efavirenz as 

an Alzheimer’s treatment. The analytical 

sleuthing that exposed the dynamics of 

the cholesterol-clearing connection was 

reported in a recent issue of the Journal of 

Biological Chemistry.

Analyses of NIST’s HDX data and 

follow-on experiments helped to explain 

why, in studies of mice, tiny doses 

of efavirenz ramped up CYP46A1’s 

cholesterol-removal capability while larger 

doses had an inhibiting effect.

The explanation: At low doses, efavirenz 

binds to a site on the enzyme that boosts 

cholesterol breakdown at another location 

on the enzyme, an increase enabled by 

changes in shape initiated by the drug. 

At higher doses, however, drug molecules 

begin to compete with cholesterol for 

the same site where cholesterol normally 

binds.

The shape-changing effect of efavirenz 

“is a classic example of a basic tenet of 

biology—structure determines function,” 

Pikuleva said. And the effect can be 

dramatic.

In mouse studies, the enzyme-drug 

connection triggered a 40 percent increase 

in cholesterol breakdown and removal 

from the brain. In people, the boost is 

likely to be significantly higher, Pikuleva 

said, since the enzyme plays a larger 

disposal role in the human brain than in 

the mouse’s.

Studies of over the past 15 years 

persuaded Pikuleva’s team to pursue an 

Alzheimer’s treatment strategy focused 

on ratcheting up the cholesterol-clearing 

capabilities of CYP46A1, part of a large 

family of iron-containing enzymes that 

strongly influence how the body processes 

drugs.

Studies by other scientists that used 

genetic manipulations in mouse models 

of Alzheimer’s disease showed that 

cranking up CYP46A1’s activity reduced 

development of plaque, or clumps of 

protein pieces called beta amyloids. These 

When efavirenz binds to CYP46A1 at the site shown in 

orange, it increases the flexibility of the protein in the 

region (magenta) around cholesterol (green). Regions 

with no changes are shown in grey and iron-containing 

heme in black. Credit: Kyle Anderson/NIST

studies also reported improvements in 

memory and learning. And, even in plaquefree, normal mice, increased cholesterol 

removal resulted in memory improvement. 

Conversely, mouse studies also found that 

suppressing CYP46A1 led to learning 

deficiencies.

Focusing on efavirenz as part of its strategy 

to “repurpose” already-approved drugs, the 

Case Western team set out to uncover how 

the drug stimulates the enzyme’s activity. 

Computational simulations and modeling 

suggested more than 30 locations on the 

enzyme where efavirenz molecule might 

bind. Seeking to winnow down the options, 

Pikuleva turned to Kyle Anderson and 

colleagues at the Institute for Bioscience 

and Biotechnology Research, a partnership 

between NIST and the University of 

Maryland.

In HDX analyses, proteins are immersed in 

“heavy water,” in which normal hydrogen, 

containing a single proton in its nucleus, 

is replaced by deuterium, a rarer type of 

hydrogen whose nucleus holds both a 

proton and neutron. Protein and heavy 

water exchange hydrogen and deuterium. 

As the protein swaps out hydrogen for 

heavier deuterium, its mass increases.

The process involves a series of steps 

that include quenching—or locking in 

the deuterium in the protein—and then 

breaking the protein into electrically 

charged fragments for analysis. With 

a device called a mass spectrometer, 

researchers can measure the mass of these 

fragments to determine how quickly 

these protein pieces exchange hydrogen 

for deuterium. A protein fragment that is 

largely exposed to water will have a fast 

exchange rate, but a fragment that comes 

from a site buried inside the protein or is 

covered up by a molecule binding to the 

protein will have a slower exchange rate.

Continued on page 14
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NEW MODEL MAY HELP SOLVE THE MYSTERY OF HOW LITHIUM STABILIZES MOODS

New measurements may have lifted the 

veil on the vexingly elusive interactions 

through which lithium can moderate 

the manic highs and debilitating lows 

experienced by people who suffer from 

bipolar disorder—about 2.6 percent of 

Americans, according to the National 

Institute of Mental Health.

Through a series of nuclear magnetic 

resonance (NMR) experiments, scientists 

from the Institute for Bioscience and 

Biotechnology Research (IBBR) and the 

Center for Biomedical Engineering and 

Technology (BioMET) at the University 

of Maryland, Baltimore, have proposed 

a new molecular model of lithium’s 

biologically active form. Writing in the 

new issue of Biophysical Journal, they also 

report evidence that this bioactive form 

can significantly prolong the activity of 

a signaling pathway in the brain’s nerve 

cells (neurons), while also connecting 

seemingly disparate results of previous 

studies of the drug.

Although not effective in all patients, 

lithium is the “first-line pharmacologic 

treatment” for acute bipolar disorder 

cases, as recommended by the American 

Psychiatric Association. But nearly 

five decades after the Food and Drug 

Administration approved lithium as a 

long-term treatment in 1970, just how 

salts formed from this common silverwhite metal work in the brain continues 

to be debated.

The new model provides a fresh 

perspective that can sharpen research 

aimed at pinning down lithium’s 

biochemical targets, and the pathways 

through which it exerts its beneficial 

psychological effects, the team explained. 

The model also could guide design of new 

treatments of mood disorders that are as 

effective as lithium but with fewer side 

effects.

“No one has yet found the binding site on 

a protein through which lithium exerts its 

pharmacological effects, which means we 

still don’t have a target that might be used 

to steer drug development,” said John 

Marino, the NIST researcher who leads 

the Biomolecular Structure and Function 

Group at IBBR, a joint institute of NIST 

and the University of Maryland. But the 

bullseye that Marino’s team found is not 

your typical binding site.

“In our model,” he explained, “lithium 

acts as a kind of force multiplier,” exerting 

the equivalent of a gentle, yet very helpful 

nudge to abundant molecular complexes 

essentially composed of phosphate and 

magnesium. In a sense, lithium may 

be a performance modulator for these 

functionally diverse complexes.

Perhaps the most ubiquitous and 

influential of these complexes is the 

molecule that serves as the body’s 

“chemical fuel” and as an essential cellular 

signaling agent—adenosine triphosphate, 

or ATP. Positively charged magnesium 

ions must bind to ATP so that cells can 

tap the energy it stores, a prerequisite for 

most biological functions and processes.

Credit: istockphoto.com

Lithium ions also have an affinity for 

phosphate-containing compounds, 

including ATP, and a number of proteins, 

known as enzymes, that use or make ATP. 

On the basis of earlier research, some 

scientists have suggested that lithium could 

compete with and displace magnesium and, 

thus, inhibit these enzymes, although the 

evidence was far from conclusive.

So, in the new study, the researchers began 

with the hypothesis that lithium could 

cooperate—or, at least, co-exist—with 

magnesium in these phosphate complexes. 

In a series of NMR experiments, which 

exploit the same magnetic properties of 

atoms that yield MRI images in hospitals 

and clinics, the team assembled evidence 

indicating that rather than competing, 

lithium ions can form an “intimate 

association” with magnesium ions and 

phosphates.

At concentrations corresponding to normal 

dosage levels, lithium ions were found to 

be attracted to ATP-magnesium to form 

an ATP-magnesium-lithium complex. 

This complex might influence how ATP 

functions in the brain and elsewhere in 

the body, the researchers reported. And 

this same three-way interaction—lithium, 

magnesium and phosphate—might 

“provide a common link among previous 

studies that have identified seemingly 

unrelated enzymes as targets for lithium 

ions,” Marino said.

One place where this interaction might be 

significant is on the surfaces of neurons, 

which have diverse cell-surface receptors 

that bind ATP. To explore this possibility, 

the team exposed rat nerve cells in a 

solution containing ATP, magnesium 

and lithium ions, separately and in 

combination. For each of these mixtures, 

Continued on page 14
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A CALL FOR DEVELOPING—AND USING—CONSENSUS STANDARDS TO ENSURE THE 

QUALITY OF CELL LINES 

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Mainstays of biomedical research, 

permanent lines of cloned cells are used 

to study the biology of health and disease 

and to test prospective medical therapies. 

Yet, all too often, these apparent pillars 

of bioscience and biotechnology crumble 

because they are crafted from faulty 

starting materials: misidentified or crosscontaminated cell lines.

Writing in the June 2016 issue of 

PLOS Biology, NIST scientists call 

for “community action” to assemble a 

“comprehensive toolkit for assuring the 

quality of cell lines,” employed at the start 

of every study.

As important, they assert, more 

researchers and laboratories should use 

the tools that already exist. The NIST 

authors point to the American National 

Standard for authentication of human cell 

lines, which can be implemented to detect 

cell-line mix-ups and contamination 

before embarking on studies of cancer or 

other research using human cells.

Unfortunately, the four-year-old standard 

has not been widely adopted, even though 

cell-line authentication is a growing 

priority among funders and publishers of 

research.

Cell lines are populations of clones: 

genetically uniform animal or plant cells 

that are bioengineered to proliferate 

indefinitely in culture. First used in the 

early 1950s, these immortalized cell lines, 

each with different properties or features, 

now number well into the thousands and 

are used as simple models for studying 

disease and for testing the toxicity of 

compounds, producing biological drugs, 

and other applications.

Cell-line contamination and 

misidentification can undermine 

research results, spur additional studies 

of questionable value and waste research 

funds—accounting for a significant 

portion of the estimated $28 billion 

of irreproducible preclinical research 

conducted each year in the United States 

alone, according to a 2015 economic 

analysis.

A “high level of confidence” in 

published research results requires 

valid underpinning data on methods 

and materials—cell lines, instrument 

performance and more, explain the 

researchers, who work in the Biosystems 

and Biomaterials Division of NIST’s 

Material Measurement Laboratory. “One 

might argue that these control data are as 

important as the study data themselves.”

The critical importance of authenticating 

cell lines is widely recognized, due, in 

part, to publicized reports on the costs 

and damaging research consequences 

of cell-line contamination, which could 

have been avoided by confirming the 

identity of cell lines at the outset of 

research projects. The National Institutes 

of Health, other funding agencies and 

organizations, and many scientific 

journals have established requirements 

for reporting on the authentication and 

purity of cell lines.

A cross-contaminated cell line, identified as such 

through STR profiling. Credit: CellBank Australia

Still, cell-line authentication is poorly 

reported. In 2015, the Global Biological 

Standards Institute reported that 52 percent 

of the life sciences researchers it surveyed 

never validate their cell lines.

The American National Standards Institute 

and American Type Culture Collection 

have developed, according to the authors, 

a “very thorough and helpful” standard on 

authenticating human cell lines using short 

tandem repeats—a DNA “fingerprinting” 

method borrowed from forensics in which 

cells can be identified by how many times 

particular DNA sequences repeat within 

their genome. “Lack of awareness,” the 

NIST authors suspect, may account for 

limited use of the standard, as suggested 

by disappointingly low levels of human 

cell-line authentication in studies. They 

recommend using the standard in training 

and education programs, which may get a 

push from authentication requirements set 

by funders and publishers.

Comparable authentication standards are 

needed for mouse, rat and other important 

nonhuman cell lines used in research and 

biomanufacturing.

The authors advocate using inclusive, 

consensus standards-setting processes—

like the one used for human cell-line 

authentication—to address these needs 

as well as to seize new opportunities that 

are arising with the commercialization of 

genome-sequencing technologies.

“Consensus standards that are produced 

in a careful, open and official process 

are an integral part of the success of this 

endeavor,” they write. “Standards help to 

assure that data are sharable and can be the 

basis of decisionmaking and compliance.”

J.L. Almeida, K.D. Cole, A.L. Plant, Standards for Cell Line 

Authentication and Beyond, PLOS Biology. June 14 (2016) 

http://dx.doi.org/10.1371/journal.pbio.1002476
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NIST AND STANFORD LAUNCH LONG-TERM MEASUREMENT INITIATIVE TO BOOST THE 

U.S. BIO-ECONOMY 

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NIST and Stanford University recently 

announced that they are embarking 

on a long-term partnership to 

develop the measurement capabilities 

central to research, innovation and 

commercialization in a budding bioeconomy of products and services in 

sectors ranging from health care to energy 

to electronics.

The new NIST-Stanford Joint Initiative 

for Metrology in Biology, or JIMB, 

brings together academia, industry 

and government to advance the 

knowledge and tools that will make 

up biotechnology’s equivalent of the 

weights and measures that enabled 

modern manufacturing and materials 

engineering. To signify JIMB’s focus on 

21st century measurement infrastructure, 

the organizations chose to launch the 

initiative on May 20th, World Metrology 

Day, which marks the anniversary 

of the Treaty of the Meter, the 1875 

international agreement on globally 

accepted units of measurement. 

“JIMB exemplifies how 21st century 

government can partner with academia 

and industry to promote the public 

good,” said Under Secretary of Commerce 

for Standards and Technology and NIST 

Director Willie E. May. “Additionally, 

I’m personally very pleased to see this 

effort come to fruition. The notion of 

NIST working together with a partner 

like Stanford to help strengthen the 

measurement foundations of biology 

and biotechnology and foster innovation 

and a marketplace that will drive future 

prosperity was the vision of my former 

bioscience advisor, Michael Amos, who 

passed away four years ago.” 

“We have long considered NIST to be a 

key public partner in advancing

Continued on page 15

Lindsay Vang (top) inspects a sequencing run of NIST Reference Material 8398, Human DNA for WholeGenome Variant Assessment (bottom), created by NIST, Stanford, and their partners in the Genome in a Bottle 

Consortium, which JIMB now manages. The reference material provides a well-characterized standard that can 

help laboratories measure the performance of the equipment, chemistry, and data analysis involved in DNA 

sequencing. Credit: T. Liepa/NIST
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AN EXTRAORDINARY STANDARD: NEW NIST PROTEIN COULD SPUR BIOPHARMACEUTICAL 

INNOVATION

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NIST recently issued one of the world’s 

most intricate measurement standards: an 

exhaustively analyzed antibody protein 

that the biopharmaceutical industry 

will use to help ensure the quality of 

treatments across a widening range of 

health conditions, including cancers, 

autoimmune disorders and infectious 

diseases.

The standard is an antibody protein—

consisting of more than 20,000 atoms—

analyzed so thoroughly that the material 

can be used by organizations around 

the globe to verify and improve their 

analytical methods for quality control.

Donated by MedImmune, the global 

biologics research and development arm 

of AstraZeneca, and then characterized 

by NIST and collaborators, the new 

reference material (RM)—NIST RM 

8671—is a monoclonal antibody, 

or mAb. This class of therapeutic 

compounds is produced in the lab 

by living cells, usually from mouse 

or hamster cell lines. Uniform in 

composition and structure, mAbs 

account for five of the 10 top-selling 

drugs and over $75 billion in annual sales 

worldwide. According to one estimate, 

about 300 monoclonal-antibody-based 

therapeutics are being evaluated for safety 

and effectiveness in clinical trials.

Antibodies work by binding to and 

inactivating proteins involved in disease 

pathways. mAbs also can act like guided 

missiles that precisely deliver therapeutic 

payloads of chemicals or radiation.

Chosen for development in consultation 

with industry, NIST RM 8671 is an 

important addition to the toolkits of 

biological drug manufacturers and their 

suppliers and regulators. It serves as a 

representative molecule that can be used 

to determine that methods for assessing 

product quality are working properly and 

to evaluate new methods or technologies.

It also provides an industry very mindful 

of intellectual property concerns with a 

standard benchmark for everyone, from 

aspiring startup to multinational firm to 

regulator.

As such, “it can serve as a common 

benchmark for future innovation,” 

explained NIST research chemist John 

Schiel, who led an international effort 

that explored and demonstrated uses 

of the reference mAb. “The material 

has many anticipated applications—in 

establishing industry-recognized best 

practices, for example—and we are 

hoping that there will be many future 

uses that we can’t predict from the current 

state of practice in biopharmaceutical 

research and production.”

A USEFUL TOOL

Industry experts have indicated that 

a universally available ‘public’ mAb, 

characterized and distributed by NIST, 

will allow better assessment of existing 

analytical methods and potentially faster 

adoption of new technologies.

In fact, the utility of the reference 

material already has been demonstrated 

by more than 100 collaborators from 

companies, regulatory agencies and 

universities around the world. As 

documented in a three-volume book set 

published by the American Chemical 

Society (ACS), the partners engaged in a 

“crowdsourcing” exercise. Research teams 

used current and emerging analytical 

methods to, in effect, take measure of the 

mAb from many different vantage points 

before NIST formally released it as a 

standard.

“NISTmAb, will act as a shared catalyst 

for developing, troubleshooting, adapting 

and bridging analytical technologies,” 

explained Oleg Borisov, director of 

analytical development at Novavax. “The 

book from ACS demonstrates this. It 

presents extensive information and data on 

a single monoclonal antibody, and describes 

the methodologies that enabled this stateof-the-art characterization. The result is 

a comprehensive characterization dossier 

that should serve as a valuable reference to 

researchers.”

Schiel, Borisov and Darryl Davis, associate 

director of biologics research at Janssen 

R&D, LLC, Pharmaceutical Companies of 

Johnson & Johnson, are editors of the set, 

State-of-the-Art and Emerging Technologies 

for Therapeutic Monoclonal Antibody 

Characterization.

Each vial of NIST RM 8671 will contain 

800 microliters of the NISTmAb at 

a concentration of 10 milligrams per 

milliliter. The standard comes with the 

results of NIST measurements that provide 

a thorough profile of the standard protein, 

Schiel said, providing details on size, 

concentration, composition, structure, 

purity, stability and other attributes.

Kurt Brorson, a research biologist in the 

Office of Biotechnology Products at the 

Food and Drug Administration (FDA), 

said the new standard can be used as a 

“universal system suitability test” for many 

of the assays and test methods used to 

assure the quality of mAbs. “The biotech 

industry can more efficiently cross-validate 

(measurement) methods at different sites or 

more efficiently develop platform analytics 

for related molecules,” he explained.

“The NISTmAb should help in answering 

a simple, yet critical, question that can 

consume a disproportionate amount of 

time when deviations arise with testing; is it 

the sample or the method that is varying?” 

said Michael Tarlov, chief of NIST’s 

Biomolecular Measurement Division and 

leader of the NIST-wide Biomanufacturing 

Program.

During the NISTmAb’s meticulously 

recorded audition, NIST and its 
| 9

collaborators developed data comparable 

to that found in a Biologics License 

Application submitted to the FDA when 

a company seeks approval for a new mAbbased therapeutic. These data are available 

online, along with results of analyses done 

with still-experimental tools, providing a 

historical record of NIST RM 8671 that 

will be updated as more analyses are done 

and as questions arise and spawn new 

studies.

Combined with the three-volume book 

set, the reference material and data 

repository provide a comprehensive—

yet updateable—picture 

of the state-of-practice in 

the fastest-growing area of 

biopharmaceuticals.

“We hope that this 

compilation serves as a baseline 

for many years of future 

collaboration, continued 

development and ultimately a 

routine analytical pipeline for 

rapid time-to-market for mAb 

therapeutics,” Schiel, Davis 

and Borisov state in the preface 

of their book set.
1 0 |

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NIST FORENSIC SCIENTIST HELPS VIETNAMESE COUNTERPARTS IDENTIFY WARTIME 

REMAINS

In a Hanoi, Vietnam, hotel conference 

room, Mike Coble led a group of 

scientists through a series of calculations. 

Coble’s presentation was heavy on the 

statistics, and this created a lot of work 

for the translators. It took two of them, 

working tag-team, to keep up.

Coble is a scientist at NIST and an 

expert in forensic DNA analysis. Before 

NIST, he was the research director at the 

U.S. Armed Forces DNA Identification 

Laboratory, where he supported U.S. 

efforts to identify the remains of 

servicemen killed in Vietnam and other 

wars. 

Today, Vietnam is undertaking a similar 

effort to identify its war dead, and Coble 

was in Hanoi this April presenting the 

latest methods to Vietnamese scientists. 

“The U.S. solved a lot of cases,” Coble 

said, including many that became solvable 

only in the last decade as research led to 

powerful new techniques for analyzing 

DNA. “But the Vietnamese are at the 

beginning of the process.” 

That process is likely to be a long one. 

The war left 300,000 Vietnamese 

unaccounted for, their remains either 

missing or unidentified. That process 

will also be a very personal one. “Many 

of the scientists who participated in the 

workshop were children during the war, 

and they and their families experienced it 

firsthand,” Coble said. 

For these scientists, the project may have 

great historical and personal significance, 

but it is also presents some difficult 

technical challenges. 

EXTRACTING INFORMATION FROM 

DEGRADED DNA 

For example, scientists create a genetic 

profile by looking at stretches of DNA 

that repeat themselves, like the same word 

typed over and over again. These sections 

are called short tandem repeats, or STRs, 

and the number of repeats in each STR 

varies from person to person. 

By measuring the length of several 

different STRs, forensic analysts generate 

a series of numbers that are like a code. 

In the FBI’s national DNA database, for 

instance, a genetic profile is made up of 

a series of numbers that can be used to 

identify an individual or vastly narrow the 

range of suspects. 

But in tropical countries such as Vietnam, 

soils tend to be acidic, which hastens 

the decomposition of DNA. When that 

happens, the STRs fall apart like a ribbon 

cut to pieces, and scientists might only 

be able to measure a handful of them—

not enough to generate a unique genetic 

profile. 

IMPROVED ACCURACY IN DNA TYPING 

Coble worked on this problem in the 

years following the events of 9/11, 

when investigators had to identify 

human remains that were exposed to 

intense heat, which also causes DNA to 

fragment. Coble and several colleagues 

at NIST identified miniSTRs—ones so 

short that they are more likely to remain 

intact even as the larger DNA fragments 

around them degrades. This advance 

allowed scientists to identify remains that 

would have otherwise been impossible to 

identify. 

Coble discussed miniSTR testing with his 

Vietnamese counterparts. The technique 

is useful in many situations. Because 

they allow for more precise and accurate 

matching, miniSTRs have also begun to 

be used in criminal investigations. For 

instance, three of the miniSTRs identified 

by NIST scientists in the years after 

9/11 will be required when uploading 

DNA profiles to the FBI’s national DNA 

database starting Jan. 1, 2017.

Continued on page 15

This DNA profile is based on 24 genetic markers (stretches of DNA found at specific locations in the genome). 

Each genetic marker contains a short tandem repeat (STR)-a section of DNA that repeats itself, like a word 

typed over and over again, with the number of repeats varying from person to person. In this graph, the 

peaks represent the number of repeats at each marker. Most markers show two peaks-one inherited from 

each parent (where only one peak appears in a marker, the individual has inherited the same number of 

repeats from each parent). These 24 markers produce a series of 48 numbers that can be used to uniquely 

identify an individual. Credit: B. Steffen/NIST
| 11

A CRACK IN THE MYSTERY OF ‘OOBLECK’—FRICTION THICKENS FLUIDS

|

By revealing missing details behind the 

odd behavior of a science fair favorite—a 

soupy mixture known as “oobleck” that 

switches back and forth between liquid 

and solid— scientists from NIST and 

Georgetown University could help to 

end a long-running scientific debate and 

improve processes ranging from pouring 

concrete to making better body armor.

Oobleck’s name is borrowed from a 

Dr. Seuss classic (Bartholomew and the 

Oobleck). Squeeze or pound it and, in an 

instant, the slurry of cornstarch and water 

becomes solid, only to revert to ooze once 

the stress is relieved.

The NIST and Georgetown scientists 

have developed a new picture to describe 

oobleck and similar mixtures of fine 

particles suspended in liquids. Based on 

flow measurements of tiny silica beads 

dispersed in solution, the model invokes 

two competing theories to explain the 

phenomenon of “shear-thickening” fluids, 

which stiffen in response to stress.

Known more formally as non-Newtonian 

substances, shear-thickening fluids 

are more than just curiosities. “They 

dictate how much stuff you can move 

and at what speed,” said Daniel Blair, a 

Georgetown University physics professor 

and co-author of an article published in 

Physical Review Letters. “In the chemical 

processing industry, you’re looking for 

the most efficient way to move something 

through a pipe, without breaking a pump. 

To do that, you want to know as much 

as you can about shear thickening so you 

can control it.”

Opposing theories—one drawing mostly 

on experimental evidence, the other on 

results of modeling studies—have been 

proposed to explain shear thickening 

in suspensions of microscopic particles, 

also called colloids. Rather than 

competing, it turns out that the two are 

complementary, according to the new 

research.

“The ongoing debate concerns the role 

of lubrication-based hydrodynamic 

interactions versus frictional contact 

forces,” explained lead author John Royer, 

a NIST materials scientist.

At low concentrations of silica beads, 

Royer, Blair and NIST materials scientist 

Steven Hudson found that measurements 

of stress were consistent with the 

hydrodynamic model. The model posits 

that impact forces particles to pack into 

assemblies called hydroclusters.

As stress increases, the hydroclusters 

contract and the fluid thickens, or 

becomes more viscous. Liquid is squeezed 

out of the clusters, creating an everthinner lubricating layer separating the 

particles and making the scattered clusters 

more rigid.

But as in earlier experiments, Royer says, 

the amount of shear thickening observed 

exceeded the levels that models indicated 

could be achieved with hydroclusters.

A competing model invokes frictional 

contacts—essentially, particle collisions 

caused by stress—as the primary driver 

of thickening. But, the friction model 

requires materials to expand—or dilate—

once stress surpasses a threshold and 

particles lock into place so that they are 

unable to squeeze by each other, as in the 

hydrodynamic model.

Therein lies the rub. Experiments to date 

have not yielded evidence of stress-caused 

expansion, leading some scientists to rule 

out friction as playing a significant role in 

shear thickening.

Royer and colleagues tackled these 

quandaries by measuring how colloids 

with different concentrations of 

bacterium-sized spheres responded to 

stresses ranging from slight to large. These 

measurements, done on a state-of-the-art 

rheometer, or flow-measurement device, 

at Georgetown’s Institute for Soft Matter 

Synthesis and Metrology, unmasked 

“a previously hidden transition from 

hydrodynamics-dominated to frictiondominated interactions as the shear 

thickening becomes more pronounced,” 

Royer says.

They found a transition from contraction 

to expansion, which occurs without 

fanfare—or no observable change in 

shear-thickening behavior itself.

“This transition demonstrates that 

shear thickening is driven primarily by 

frictional contacts, with hydrodynamic 

forces playing a supporting role at 

lower concentrations of particles, when 

mixtures are less dense,” Royer explained. 

“These results now motivate new 

microscopic approaches to control shear 

thickening in industrial applications, by 

either minimizing thickening when steady 

flow is needed or controlling thickening 

for use as in flexible body armor 

applications.”

Protective clothing applications under 

development aim to exploit shear 

thickening to, for example, strengthen 

defense against knife wounds in the case 

of body armor and to further enhance 

protection against penetration by 

projectiles and blast debris.

J.R. Royer, D.L. Blair and S.D. Hudson, A rheological 

signature of frictional interactions in shear thickening 

suspensions, Physical Review Letters, 5 May (2016). 

http://dx.doi.org/10.1103/PhysRevLett.116.188301

Credit: istockphoto.com
1 2 |

|

HOW DO NATURE’S MATERIALS STACK UP? “PATCHY” FRAMEWORK OFFERS NEW 

INSIGHTS INTO SELF-ASSEMBLY

Nature’s toolkit includes its still-matchless 

ability to effortlessly assemble proteins, 

membranes and other complex structures 

from parts of atoms, molecules, and 

particles of various sizes and shapes. 

Researchers have worked for several 

decades to understand the mechanisms 

behind this almost magic-like 

construction process.

New research, published by scientists at 

NIST and a colleague, moves researchers 

a big step toward the aim of devising 

comprehensive theories and realistic 

models of self-assembly. The advances 

provide insights to guide efforts to harness 

and manage self-assembly in artificial 

materials and reliably make structures as 

designed. These could include entirely 

new structures composed of subunits 

specially tailored to self-assemble in 

predictable ways. Similarly, the work 

could help prevent unwanted structures 

from forming, a concern especially during 

the production of biopharmaceuticals. 

Debra Audus, a NIST materials scientist, 

and two colleagues have come up with 

a new approach for predicting the 

clustering behavior of particles in fluids, 

an environment in which self-assembly 

frequently occurs. They describe their 

theoretical framework in a recent issue of 

the Journal of Chemical Physics. 

Applying the framework to experimental 

results, other researchers can cut to the 

chase more quickly and predict the shape, 

size and distribution of particle clusters as 

conditions change in liquid mixtures. 

Audus, NIST materials scientist Jack 

Douglas and Francis Starr of Wesleyan 

University in Connecticut added 

another layer of realism to a so-called 

patchy particle model, a popular tool 

for investigating how particles interact 

in liquids. These models are simplified 

representations that show how interparticle forces steer self-assembly 

Model patchy particles self-assemble and provide 

guidance for understanding the nature of self-assembly 

in more complicated systems such as protein solutions.

Credit: Audus/NIST (made with VMD)

For one, they determined that their 

five-patch particles behaved like swollen, 

branched polymers, a well-studied class of 

materials. The researchers also identified the 

thermodynamic conditions under which 

self-assembly behavior will emerge, and 

they describe methods for determining the 

average molecular weight of clusters and 

their size distribution. 

Employing these methods, other researchers 

can probe the behavior of particles in 

solution by measuring how they scatter 

light, for example, and compare their results 

to patchy particle models. For instance, 

do the experimental particles behave like 

theoretical particles with five patches, rather 

than seven? 

“From there, researchers can use theory to 

predict how particles in their mixtures will 

cluster under different conditions,” Audus 

explained. “With our framework, they can 

gain insights into clustering phenomena.” 

D.J. Audus, F.W. Starr, and J.F. Douglas, Coupling of isotropic 

and directional interactions and its effect on phase separation 

and self-assembly, Journal of Chemical Physics 144, 074901 

(2016). http://dx.doi.org/10.1063/1.4941454

processes. They can streamline efforts 

to identify the basic principles at work, 

saving researchers from having to piece 

them together through trial-and-error 

experiments. 

Typically, patchy particles are spheres 

whose surfaces are precisely “decorated” 

with several patches—each possessing 

a directional attractive force, or bond. 

Usually, the models stop there, but the 

team went one better. They cloaked their 

five-patch particles with a pervasive, 

uniform force—akin to the ubiquitous 

van der Waals forces arising from 

molecular interactions. Though feeble, 

these attractive forces exert significant 

influence on the ultimate shape of multiparticle structures. 

Including both types of forces in the 

model set the stage for a dynamic 

competition that defined where cluster 

formation and self-assembly occur, Audus 

explained. 

Changing the size of the particleencompassing attractive force significantly 

altered how particles were distributed 

into areas of low and high concentration, 

also known as phases. As the uniform 

force increased, the temperature at which 

particles began to separate also increased, 

and the region where self-assembly took 

place decreased. These relationships were 

revealed through a computer-intensive 

simulation method used to explore 

the behavior of complex and often 

disordered systems through repeated 

random sampling. Crunching numbers 

to measure the behavior of some particles 

as they separated into phases engaged 

multiple computers for nearly a month—

testimony to the bewildering intricacies of 

self-assembly. 

From there, the team used a theoryguided approach to distill the simulation 

results and look for overarching lessonslearned that other researchers can apply. 
| 1 3

SIMPLER, FASTER, AND CHEAPER: A FULL-FILLING APPROACH TO MAKING CARBON 

NANOTUBES OF CONSISTENT QUALITY

|

Just as many of us might be resigned to 

clogged salt shakers or rush-hour traffic, 

those working to exploit the special 

properties of carbon nanotubes have 

typically shrugged their shoulders when 

these tiniest of cylinders fill with water 

during processing. But for nanotube 

practitioners who have reached their 

Popeye threshold and “can’t stands 

no more,” NIST has devised a cheap, 

quick, and effective strategy that reliably 

enhances the quality and consistency of 

the materials—important for using them 

effectively in applications such as new 

computing technologies.

To prevent filling of the cores of singlewall carbon nanotubes with water or 

other detrimental substances, the NIST 

researchers advise intentionally prefilling 

them with a desired chemical of known 

properties. Taking this step before 

separating and dispersing the materials, 

usually done in water, yields a consistently 

uniform collection of nanotubes. In 

quantity and quality, the results are 

superior to water-filled nanotubes, 

especially for optical applications such as 

sensors and photodetectors.

The approach opens a straightforward 

route for engineering the properties of 

single-wall carbon nanotubes—rolled 

up sheets of carbon atoms arranged like 

chicken wire or honey combs—with 

improved or new properties.

“This approach is so easy, inexpensive 

and broadly useful that I can’t think of a 

reason not to use it,” said NIST chemical 

engineer Jeffrey Fagan.

In their proof-of-concept experiments, 

the NIST team inserted more than 20 

different compounds into an assortment 

of single-wall carbon nanotubes with an 

interior diameter that ranged from more 

than 2 down to about 0.5 nanometers. 

Led by visiting researcher Jochen Campo, 

the scientists tested their strategy by using 

hydrocarbons called alkanes as fillers.

The alkanes, which include such familiar 

compounds as propane and butane, 

served to render the nanotube interiors 

unreactive. In other words, the alkanefilled nanotubes behaved almost as if they 

were empty—precisely the goal of Campo, 

Fagan, and colleagues.

Compared with nanotubes filled with 

water and possibly ions, acids and other 

unwanted chemicals encountered during 

processing, empty nanotubes possess 

far superior properties. For example, 

when stimulated by light, empty carbon 

nanotubes fluoresce far brighter and with 

sharper signals.

Yet, “spontaneous ingestion” of water or 

other solvents by the nanotubes during 

processing is an “endemic but often 

neglected phenomenon with strong 

implications for the development of 

nanotube applications,” the NIST team 

wrote in a recent article in Nanoscale 

Horizons.

Perhaps because of the additional cost 

and effort required to filter out and gather 

nanotubes, researchers tend to tolerate 

mixed batches of unfilled (empty) and 

mostly filled single-wall carbon nanotubes. 

Separating unfilled nanotubes from these 

mixtures requires expensive ultracentrifuge 

equipment and, even then, the yield is 

only about 10 percent, Campo estimates.

“If your goal is to use nanotubes for 

electronic circuits, for example, or for 

fluorescent anti-cancer image contrast 

agents, then you require much greater 

quantities of materials of consistent 

composition and quality,” Campo 

explained, who was exploring these 

applications while doing postdoctoral 

research at the University of Antwerp. 

“This particular need inspired 

development of the new prefilling method 

by asking the question, can we put some 

passive chemical into the nanotube instead 

to keep the water out.”

From the very first simple experiments, 

the answer was yes. And the benefits 

can be significant. In fluorescence 

experiments, alkane-filled nanotubes 

emitted signals two to three times stronger 

than those emitted by water-filled 

nanotubes. Performance approached that 

of empty nanotubes—the gold standard 

for these comparisons.

As important, the NIST-developed 

prefilling strategy is controllable, versatile, 

and easily incorporated into existing 

methods for processing single-wall carbon 

nanotubes, according to the researchers.

J. Campo, Y. Piao, S. Lam, C.M. Stafford, J.K. Streit, J.R. 

Simpson, A.R. Hight Walker and J.A. Fagan, Enhancing 

single-wall carbon nanotube properties through controlled 

endohedral filling, Nanoscale Horizons, Published online 

May 10 (2016). http://dx.doi.org/10.1039/C6NH00062B

To prevent cores of single-wall carbon nanotubes 

from filling with water or other detrimental 

substances, the NIST researchers advise intentionally 

prefilling them with a desired chemical of known 

properties. Taking this step before separating and 

dispersing the materials, usually done in water, 

yields a consistently uniform collection of nanotubes, 

especially important for optical applications. 

Credit: Fagan/NIST.
1 4 |

|

SHAPE-CHANGING ENZYME SUGGESTS HOW SMALL DOSES OF ANTI-HIV DRUG MIGHT 

TREAT ALZHEIMER’S DISEASE (CONT’D.)

“HDX mass spectrometry opens 

a window that allows you to look 

in on how proteins behave under 

physiologically relevant conditions,” 

Anderson explained. “It provides the 

pieces to a puzzle that you can assemble 

to show how their three-dimensional 

shape changes over time.”

The NIST team used HDX to compare 

and contrast CYP46A1 in four different 

states: alone, with cholesterol only, with 

efavirenz only, and with cholesterol and 

efavirenz. Subsequent analyses of the 

resulting torrents of experimental data—a 

computationally intensive process that 

Anderson performed in triplicate to ensure 

accuracy—revealed not only where the 

drug attached to the enzyme but also how 

the cholesterol-binding site adjusted in 

response. The structural changes enabled 

CYP46A1 to bind cholesterol molecules 

more tightly than in the absence of the 

drug.

Following up with a study using a 

different method, Pikuleva’s team further 

confirmed the site of efavirenz binding 

as determined with HDX. The evidence 

strongly suggests, she said, at doses a 

hundred times lower than prescribed 

for treating HIV, efavirenz might be 

an effective therapy for stimulating 

cholesterol turnover from the brain and 

slowing or preventing Alzheimer’s disease.

Pikuleva and colleagues now are seeking 

to obtain funding for a clinical trial on 

humans to investigate the effects of small 

doses of efavirenz.

K.W. Anderson, N. Mast, J.W. Hudgens, J.B. Lin, 

I.V. Turko and I.A. Pikuleva, Cholesterol Hydroxylase 

CYP46A1: Mapping of the Allosteric Site for Efavirenz, a 

Drug that Stimulates Enzyme Activity, Journal of Biological 

Chemistry, May 27 (2016). http://dx.doi.org/10.1074/jbc.

M116.723577

NEW MODEL MAY HELP SOLVE THE MYSTERY OF HOW LITHIUM STABILIZES MOODS 

(CONT’D.)

|

they monitored the behavior of a 

type of ATP receptor that opens a 

channel to allow the flow of calcium 

ions into the neurons, a key activity 

in neuronal signaling. All elicited the 

same initial response. However, the 

ATP-magnesium-lithium combination 

caused the receptor to remain activated 

40 percent longer than did the ATPmagnesium stimulus. Whether and 

how this prolonged signaling response 

contributes to lithium’s mood-stabilizing 

effects remains to be studied.

“We’re not saying this is the whole 

story. There’s a broad swath of other 

possibilities, as well,” Marino said. 

“But this physical model provides an 

intriguing new way to broadly view 

lithium’s bioactive form—as working in 

tandem with magnesium by co-binding 

to phosphate-containing ligands, and 

thereby influencing the function of cellular 

receptors and enzymes.”

K.T. Briggs, G.G. Giulian, G. Li, J.P.Y. Kao and J.P. Marino, 

A Molecular Model for Lithium’s Bioactive Form, Biophysical 

Journal, 26 July (2016). http://dx.doi.org/10.1016/j.

bpj.2016.06.015
| 1 5

|

NIST FORENSIC SCIENTIST HELPS VIETNAMESE COUNTERPARTS IDENTIFY WARTIME 

REMAINS (CONT’D.)

But for one week in April, Coble stepped 

away from his research at NIST to share 

his knowledge. It was his first trip to 

Vietnam. 

Coble’s trip was organized by the 

International Criminal Investigative 

Training Assistance Program of the U.S. 

Department of Justice, which helps 

foreign governments develop professional 

and transparent law enforcement 

institutions. That program is funded 

by the U.S. Agency for International 

Development, the U.S. Department 

of State, and the U.S. Department of 

Defense. 

A SHARED LANGUAGE 

If it’s true that war can dehumanize 

one’s enemies, then perhaps giving fallen 

enemies a name can humanize them 

again. If so, Coble’s trip, and other efforts 

like it, are especially fitting gestures of 

peace between formerly warring nations. 

In fact, the assistance that Coble offered 

the Vietnamese runs in both directions. 

When U.S. specialists excavate sites in 

Vietnam to search for the remains of 

U.S. servicemen, Vietnamese experts 

participate in the work. 

But whatever the deeper meaning of 

this exchange, Coble said that in the 

classroom, it was just a bunch of scientists 

sharing ideas. 

“We didn’t speak the same language, and 

we didn’t have the same experience in 

terms of history,” Coble noted. “But we 

were speaking the language of science, and 

that helped to transcend the differences.”

NIST AND STANFORD LAUNCH LONG-TERM MEASUREMENT INITIATIVE TO BOOST THE 

U.S. BIO-ECONOMY (CONT’D.)

|

biomeasurement science,” said Dr. Ann 

Arvin, Stanford’s vice provost and dean 

of research. “We are delighted that 

NIST is now establishing a permanent 

West Coast presence to help advance 

basic science and promote innovative 

commercial developments.” 

JIMB sprouted from an initial 

three-year collaboration focused on 

biological measurements. Thanks to 

these research connections, JIMB 

begins with a complement of 16 NIST 

staff members. They include NIST 

postdoctoral researchers embedded 

in Stanford faculty members’ labs. 

In addition, eight Stanford graduate 

students are supported by NIST 

grants that encourage research that 

integrates measurement and biological 

engineering objectives. 

“To realize biotechnology’s tremendous 

promise, we need to develop 

measurement platforms—standards, 

methods, and data—that support 

innovation within existing and entirely 

new industries,” said Laurie Locascio, 

director of NIST’s Material Measurement 

Laboratory. “Stanford’s strong 

relationships with area biotechnology 

companies will continue to inform JIMB’s 

work so that it is as widely applicable as 

possible.” 

The partnership already has yielded 

practical benefits, including the world’s 

first reference material to help ensure 

laboratories accurately “map” DNA 

for genetic testing, medical diagnoses, 

and future customized drug therapies. 

The “measuring stick” for the human 

genome—NIST RM 8398—was created 

by NIST, Stanford, and their partners 

in the Genome in a Bottle Consortium, 

which JIMB now manages. 

Since it was issued in May 2015, NIST’s 

reference human genome has been helping 

medical labs to ensure the accuracy of 

genetic tests. The reference material also 

served as the comparative tool that the 

Food and Drug Administration used in 

its PrecisionFDA Consistency Challenge. 

Intended to improve the reliability, accuracy,

and utility of DNA testing, the challenge 

is a key element of President Obama’s 

Precision Medicine Initiative. 

Besides Genome in a Bottle, two other 

NIST-hosted consortia—Synthetic Biology 

Standards and External RNA Controls—

provide direct means for companies and 

other organizations to engage with JIMB. 

Initially, JIMB will focus on human genome 

sequencing and synthetic biology. NIST is 

in the process of establishing a West Coast 

facility where researchers will develop and 

prototype biometrology tools and produce 

validated tools and reagents for the biology 

sector. 
1 6 |

OUTREACH AND PARTNERING

MML PART OF NEW NATIONAL 

MICROBIOME INITIATIVE, RECEIVES FDA 

GRANT

MML’s program in microbiome 

metrology, led by Scott Jackson, is part of 

the new National Microbiome Initiative, 

announced by the White House Office 

of Science and Technology Policy in May 

2016. The initiative will help advance 

microbiome applications for health care, 

food safety and security, environmental 

protection, bioenergy production, and 

other areas.

Also in microbiome news, MML 

received a grant from the Food and 

Drug Administration’s (FDA) Center for 

Devices to develop a mixed-pathogen 

DNA reference material so that 

developers of new diagnostic tools can 

assess analytical sensitivity, specificity, 

and relative performance of pathogen 

detection devices and assays that use next 

generation sequencers. 

MML EXPERTISE TO HELP ADVANCE 

SYNTHETIC GENOME

MML’s Elizabeth Strychalski attended 

the invitation-only HGP-write: Testing 

Large Genomes in Cells meeting in May 

2016, to contribute to discussion of the 

underlying technology and knowledge 

required to design and create synthetic 

human genomes, which have the 

potential to lead to innovative medical 

treatments and platforms for research 

and production of new materials, energy 

feedstocks, and sources of nutrition. 

NIST’s expertise in synthetic and 

engineering biology will help meet critical 

measurement needs to realize this vision. 

RISK ASSESSMENT TO MOVE 

NANOTECHNOLOGIES TO THE NEXT LEVEL

The White House’s National 

Nanotechnology Initiative is moving 

into its next phase. MML’s Elijah 

Petersen chaired a breakout session 

at the initiative’s 2016 Strategic 

Planning Stakeholder Workshop on 

“Risk Throughout the Product Life 

Cycle.” Participants discussed the need 

for measurement methods to assess 

the environmental, health, and safety 

implications of nanomaterials with 

increased complexity.

GENOME EDITING WORKSHOP EXPLORES 

MEASUREMENT NEEDS

In early May 2016, MML’s Samantha 

Maragh hosted the first Genome Editing 

Standards Workshop, in partnership 

with the American Society of Gene 

and Cell therapy and sponsored by 

Microsoft Corporation and Editas 

Medicine. Participants from FDA, 

NIH, academia, and industry discussed 

measurement assurance needs to help 

genome editing mature into a tool for the 

study and treatment of human disease. 

Participants discussed FDA requirements; 

increasing confidence in editing, sample 

measurements, and assessment of offtarget edits; and informatics needs. 

SUPPORT FOR STEM EDUCATION

MML’s Jeanita Pritchett returned to 

Grahamstown, South Africa, where she 

served as an Embassy Science Fellow in 

2015, for SciFest Africa 2016, South 

Africa’s largest national science festival. 

Pritchett coordinated the Workshop 

and Etcetera portions of the program. 

Pritchett also performed a number of 

demos at iRhini Township Festival and 

at the Nelson Mandela Bay Science 

Center (Uitenhage, South Africa) for 

students and teachers that could not 

attend SciFest. As part of the United 

States Diplomatic Mission to South 

Africa, Pritchett also presented at the 

Nelson Mandela Metropolitan University 

alongside scientists from NASA and other 

organizations.

KEYNOTES

MML’s Edward Garboczi delivered the 

Frontiers of Engineering lecture in May 

2016 at the Leeds University School of 

Chemical and Process Engineering in the 

United Kingdom, explored their worldrenowned complex particulate products 

and processes research area, and initiated 

several potential collaborations in the area 

of particle shape, which is vital to additive 

manufacturing. 

Rebecca Pugh, leader of the joint 

Environmental Specimen Bank at 

Hollings Marine Lab (a partnership 

among NIST, the National Oceanic 

and Atmospheric Administration, the 

South Carolina Department of Natural 

Resources, the College of Charleston, 

and the Medical University of South 

Carolina) gave the keynote address at 

the Trends and Advancements in the 

Sampling and Preservation of Samples 

for the Identification of Contaminants 

of Emerging Concern Workshop held in 

March 2016 at the Norwegian Institute 

for Water Research.
| 1 7

WISE SELECTED FOR 2015 

HILLEBRAND PRIZE

Stephen A. Wise, who recently retired 

after 40 years of service to NIST, is 

the recipient of the 2015 Hillebrand 

Prize from the Chemical Society of 

Washington. The annual Hillebrand 

Prize, awarded for original contributions 

to the science of chemistry, is named 

for William F. Hillebrand (1853-1925), 

former chief chemist at NIST. Wise is 

recognized for career achievements in 

separation science, particularly in the 

field of polycyclic aromatic hydrocarbons, 

and for contributions to the NIST 

Standard Reference Materials (SRM) 

Program in support of an accurate 

national measurement system for 

chemistry. Wise has been involved in the 

development of over 90 SRMs to support 

accurate measurement of environmental 

contaminants in such varied matrices as 

air and diesel particulate matter, coal tar, 

sediments, mussel tissues, fish oil and 

tissues, whale blubber, human serum and 

milk, and house dust. In the mid-1990s, 

he facilitated development of food SRMs 

to support newly issued food labeling 

regulations. He also provided leadership 

in establishing the critical partnerships 

among NIST, the National Institutes of 

Health Office of Dietary Supplements, 

FDA, and other stakeholders to 

produce reference materials for dietary 

supplements.

FASOLKA, SATTERFIELD RECOGNIZED BY WASHINGTON ACADEMY OF SCIENCES

AWARDS

MML Deputy Director Mike Fasolka 

received the Washington Academy of 

Sciences 2016 Award for Engineering 

Sciences, in recognition of his 

exceptional research contributions 

to the field of materials science and 

engineering and his influential and 

sustained technical leadership in the 

global materials science enterprise. 

MML Chief of Staff Mary Satterfield 

received the 2016 Krupsaw Award for 

Non-Traditional Teaching in recognition 

of her groundbreaking work in creating 

a series of programs to educate students, 

teachers, and NIST staff members in 

measurement science. Both Fasolka 

and Satterfield were also recognized as 

fellows of the Washington Academy of 

Sciences.

MML-AUTHORED ARTICLE SELECTED AS EDITOR’S PICK

An article by MML scientists published 

in the Journal of Vacuum Science and 

Technology A was recently featured as an 

Editor’s Pick and appears in the “Most 

Read” list on the journal’s website. A 

write-up of the article appeared in the 

Publication Highlights section of the 

May 2016 edition of the “Beneath the 

AVS Surface” newsletter. The article, by 

Tariq Ahmido, William Kimes, Brent 

Sperling, Joseph Hodges, and James 

Maslar and entitled “In-Situ Metrology 

to Characterize Water Vapor Delivery 

during Atomic Layer Deposition” (J. 

Vac. Sci. Technol. A 34, 031512 [2016]), 

describes the performance of an in 

situ tunable diode laser absorption 

spectroscopy scheme for performing 

rapid, quantitative measurements of 

water vapor in a gas delivery system 

representative of those employed in 

laboratory and commercial atomic 

layer deposition systems. This work 

demonstrates that such a metrology 

could provide the basis for the 

development of a mass flow meter 

for use in closed-loop control of 

water delivery during thin film metal 

oxide deposition processes. Such 

control would allow a decrease in 

the range of film properties obtained 

during microelectronics fabrication 

processes, which could potentially 

lead to an increase in device yield 

and performance.
1 8 |

FOR LABORATORY USE ONLY

NIST STANDARD STORY

WHAT

Standard Reference Material® 1849a, 

Infant/Adult Nutritional Formula

Each packet contains approximately 10 

grams of a milk-based powder, a blend of 

material similar to the infant and adult 

versions of just-add-water nutritional 

powders you can buy in the grocery store. 

The material, provided by a manufacturer, 

is close to the consumer versions, but is 

“not an actual infant formula, because 

you don’t want it to be confused with 

anything real,” says Melissa Phillips, one 

of the NIST scientists who coordinated 

the analysis of this reference material. 

It’s not so important that the material 

matches an actual consumer product, just 

that it’s been assessed with NIST’s usual 

rigor and is available for others to do the 

same. 

WHY

Infant formula is “one of the most 

regulated foods in the world,” according 

to Phillips, “with strict requirements for 

how much of each nutrient the powders 

should contain. When manufacturers 

report those nutrient values to regulators, 

they have to be within a narrow range, so 

manufacturers need accurate and precise 

analytical methods.” Manufacturers seek 

guidance from AOAC International, 

which works with food manufacturers, 

among many other sectors, to set 

industry standards. While NIST is not a 

regulatory body, its scientists participate 

in AOAC standards committees alongside 

manufacturers to understand their 

needs. NIST then develops reference 

materials to help manufacturers comply 

with regulations both in the U.S. and in 

foreign markets, so that their products 

can be exported. Manufacturers like it 

when NIST provides reference materials 

and data because they can trust NIST’s 

products are free of bias that might favor 

a competitor. This reference material 

continues work that NIST has done 

since the 1990s to support formula 

manufacturers.

WHO

NIST scientists collaborated with the 

Grocery Manufacturers Association to 

organize more than a dozen laboratories 

in a round robin, an interlaboratory 

comparison test where all the participants 

test the same material with the same 

methods and the results are compared. 

The data contributes to the calculation 

of values for each nutrient analyzed, and 

NIST scientists have thoroughly measured and characterized more than 1,300 physical products, NIST Standard Reference 

Materials®, to help people in industry, academia, and government agencies calibrate instruments, verify their test methods, and 

develop new measurement methods. NIST reference materials, for example, help manufacturers make interoperable parts in far-flung 

facilities, medical labs check the accuracy of cholesterol and other clinical tests, and scientists monitor environmental threats.

helps NIST understand what kind of 

values to expect from the typical industry 

test methods in daily use.

HOW

Manufacturers and testing labs use 

Standard Reference Material 1849a to 

validate their methods, or to confirm the 

composition of the in-house reference 

materials they make themselves for 

validating their analytical methods. The 

NIST reference material is also used when 

two manufacturers or other test labs don’t 

agree on the values in a sample. To settle 

the dispute, they’ll use Standard Reference 

Material 1849a and AOAC official 

methods to understand which method 

needs correcting. About 550 units of 

Standard Reference Material 1849a are 

sold each year.

Learn more: https://www-s.nist.gov/

srmors/view_detail.cfm?srm=1849a

Technical Contacts: 

Melissa Phillips, melissa.phillips@nist.gov

Laura Wood, laura.wood@nist.gov
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PUBLICATIONS

D. F. Sunday, A. F. Hannon, S. Tein, 

R. J. Kline, “Thermodynamic and 

Morphological behavior of block 

copolymer blends with thermal polymer 

additives” Macromolecules, 

(12-Jul-2016) 

M. Mortimer, E. J. Petersen, B. 

A. Buchholz, E. Orias, P. Holden, 

“Bioaccumulation of Multiwall Carbon 

Nanotubes in Tetrahymena thermophila 

by Direct Feeding or Trophic Transfer” 

Environmental Science & Technology, 

(11-Jul-2016) 

J. E. Seppala, K. D. Migler, “Infrared 

thermography of welding zones 

produced by polymer extrusion additive 

manufacturing” Additive Manufacturing, 

(02-Jul-2016) 

E. Mansfield, I. H. Bell, S. L. Outcalt, 

“Bubble Point Measurements of 

n-Propane + n-Decane Binary Mixtures 

with Comparisons of Binary Mixture 

Interaction Parameters for Linear 

Alkanes” Journal of Chemical and 

Engineering Data, (01-Jul-2016) 

T. P. Forbes, E. R. Sisco, C. Browne, 

“Detection and identification of sugar 

alcohol sweeteners by ion mobility 

spectrometry” Analytical Methods, Vol. 8, 

pp. 5611-5618, (23-Jun-2016) 

S. Henriette, R. Handy, T. Fernandes, S. 

Klaine, E. J. Petersen, “Nanomaterials in 

the aquatic environment: An EU-USA 

perspective on the status of ecotoxicity 

testing, research priorities and challenges 

ahead” Environmental Toxicology and 

Chemistry, (19-Jun-2016) 

R. A. Maier, “Low Temperature 

Ionic Conductivity of an Acceptor 

Doped Perovskite Part II: Impedance 

Spectroscopy of Single Crystalline 

BaTiO3” Journal of the American Ceramic 

Society, 7 pp., (16-Jun-2016) 

C. G. Simon Jr., A. L. Plant, S. Sarkar, J. 

T. Elliott, S. Lin-Gibson, “Strategies for 

Achieving Measurement Assurance for 

Cell Therapy Products” Science, Vol. 5, 

pp. 705-708, (01-Jun-2016) 

L. M. Pitkanen, A. M. Striegel, 

“Determining the core, corona, and total 

size of CdSeS/ZnS quantum dots by 

SEC/QELS and TEM” Analytical and 

Bioanalytical Chemistry, (21-May-2016) 

H. W. Hatch, W. P. Krekelberg, S. 

D. Hudson, V. K. Shen, “DepletionDriven Crystallization of Cubic Colloids 

Sedimented on a Surface” Journal of 

Chemical Physics, pp. 194902-1-194902-

12, (19-May-2016) 

J. R. Royer, D. L. Blair, S. D. Hudson, 

“A rheological signature of frictional 

interactions in shear thickening 

suspensions” Physical Review Letters, Vol. 

116, 13 pp., (05-May-2016) 

A. Chremos, J. F. Douglas, “Influence 

of Higher Valence Ions on Flexible 

Polyelectrolytes Stiffness and Counter-ion 

Distribution” Journal of Chemical Physics, 

Vol. 144, (28-Apr-2016) 

M. M. Schantz, D. Cleveland, N. A. 

Heckert, J. R. Kucklick, S. D. Leigh, S. 

E. Long, J. M. Lynch, K. E. Murphy, R. 

Oflaz, A. L. Pintar, B. J. Porter, S. A. Rabb, 

S. S. Vander-Pol, S. A. Wise, R. L. Zeisler, 

“Development of Two Fine Particulate 

Matter Standard Reference Materials 

(<4 μm and <10 μm) for the Determination 

of Organic and Inorganic Constituents” 

Analytical and Bioanalytical Chemistry, 

(13-Apr-2016) 

H. W. Hatch, S. Y. Yang, J. Mittal, V. K. 

Shen, “Self-Assembly of Trimer Colloids: 

Effect of shape and interaction range” 

Soft Matter, Vol. 12, No. 18, pp. 4170-

4179, (05-Apr-2016) 

J. T. Hodges, B. J. Drouin, D. C. Benner, 

L. Brown, M. J. Cich, T. Crawford, M. 

Devi, A. Guillaume, E. Mlawer, D. J. 

Robichaud, O. Fabiano, K. Sung, W. 

Edward, S. Yu, “Multispectrum analysis of 

the Oxygen A-band” Journal of Quantitative 

Spectroscopy and Radiative Transfer, 

(25-Mar-2016)
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