Culture

Ghost imaging speeds up super-resolution microscopy

video: The new microscopy approach involves an optical component known as a random phase modulator, which turns fluorescence from the sample into a random speckle pattern. Coding the fluorescence in this way allows each pixel of a very fast CMOS camera to collect light intensity from the whole object in a single frame. To form the image via ghost imaging and compressive imaging, this light intensity is correlated with a reference light pattern in a single step.

Image: 
Zhongyang Wang, Chinese Academy of Sciences

WASHINGTON -- Researchers have used advanced imaging approaches to achieve super-resolution microscopy at unprecedented speeds. The new method should make it possible to capture the details of processes occurring in living cells at speeds not previously possible.

Super-resolution techniques, often called nanoscopy, achieve nano-scale resolution by overcoming the diffraction limit of light. Although nanoscopy can capture images of individual molecules inside cells, it is difficult to use with living cells because hundreds or thousands of imaging frames are needed to reconstruct an image -- a process too slow to capture quickly changing dynamics.

In Optica, The Optical Society's (OSA) journal for high impact research, investigators from the Chinese Academy of Sciences describe how they used the unconventional imaging approach known as ghost imaging to enhance the imaging speed of nanoscopy. The combination produces nanometer resolution using orders of magnitude fewer imaging frames than traditional nanoscopy techniques.

"Our imaging method can potentially probe dynamics occurring on millisecond time-scales in subcellular structures with spatial resolution of tens of nanometers - the spatial and temporal resolution at which biological processes take place," said Zhongyang Wang, co-leader of the research team.

Combining techniques for faster imaging

The new approach is based on stochastic optical reconstruction microscopy (STORM), which was one of three super-resolution techniques to be recognized with Nobel prizes in 2014. STORM, which is also sometimes called photoactivated localization microscopy (PALM), is a wide-field technique that uses fluorescent labels that switch between light-emitting (on) and dark (off) states. Acquiring hundreds or thousands of snapshots, each capturing the subset of fluorescent labels that are on at a given time, allows the location of each molecule to be determined and used to reconstruct a fluorescence image.

The researchers turned to ghost imaging to speed up the STORM imaging process. Ghost imaging forms an image by correlating a light pattern that interacts with the object with a reference pattern that does not. Individually, the light patterns don't carry any meaningful information about the object. The researchers also used compressive imaging, a computational approach that enables image reconstruction with fewer exposures because it uses an algorithm to fill in the missing information.

"While STORM requires a low density of fluorescent labels and many image frames, our approach can create a high-resolution image using very few frames and a high density of fluorophores," said co-leader of research team Shensheng Han. "It also doesn't need any complex illumination, which helps reduce photobleaching and phototoxicity that could harm dynamic biological processes and living cells."

Improving imaging efficiency

To implement the new technique, the researchers used an optical component known as a random phase modulator to turn fluorescence from the sample into a random speckle pattern. Coding the fluorescence in this way allowed each pixel of a very fast CMOS camera to collect light intensity from the whole object in a single frame. To form the image via ghost imaging and compressive imaging, this light intensity was correlated with a reference light pattern in a single step. The result was more efficient image acquisition and a reduction in the number of frames required to form a high-resolution image.

The researchers tested the technique by using it to image a 60-nanometer ring. The new nanoscopy approach could resolve the ring using just 10 image frames while traditional STORM approaches needed up to 4000 frames to achieve the same result. The new approach also resolved a 40-nanometer ruler with 100 image frames.

"We hope this method can be applied to a variety of fluorescent samples, including those that exhibit weaker fluorescence than those used in this research," said Wang. The researchers also want to make the technique faster to achieve video-rate imaging with a large field of view and plan to use it to acquire 3D and color images.

Credit: 
Optica

University of Miami team investigates why candidates for cochlear implants rarely get them

image: Sandra Prentiss, Ph.D., CCC-A, assistant professor of otolaryngology at the University of Miami Miller School of Medicine and lead author of the study

Image: 
University of Miami Miller School of Medicine

Many hearing loss patients are cochlear implant candidates, but few use this technology that could improve their hearing and quality of life.

University of Miami and University of Michigan researchers looked into why. Their results were published Dec. 12 in JAMA Otolaryngology-Head and Neck Surgery.

Researchers surveyed U.S. audiologists from academic centers, hospitals and large cochlear implant centers, asking how they preoperatively assess adults for cochlear implant candidacy. Based on the 92 completed surveys analyzed for the study, the findings were "eye opening," according to the paper's lead author, Sandra Prentiss, Ph.D., CCC-A, assistant professor of otolaryngology at the University of Miami Miller School of Medicine.

"Currently, cochlear implant candidacy testing protocols are not streamlined. The survey identified wide variability in how clinics and providers are determining candidacy for patients who may benefit from the technology," Dr. Prentiss said. "The problem is that if there is too much variance, potential candidates will not have the same access to this good treatment option."

Cochlear implants are a greatly under-utilized treatment for hearing loss. Dr. Prentiss said fewer than 9% of people who are candidates for cochlear implants use this technology. Part of the reason appears to be that the criteria for candidacy have changed in recent years and many providers do not know about the changes or have not implemented them in practice.

"Fifteen years ago, candidacy was pretty straightforward in that only people with severe-to-profound hearing loss were candidates," Dr. Prentiss said.

Advances in surgical technique and electrode design have improved outcomes among cochlear implant patients. As a result, the FDA has expanded the criteria for cochlear implants to include people with lesser degrees of hearing loss. This includes elderly people with age-related hearing loss who have not benefited from hearing aids, according to Dr. Prentiss.

"We found that some audiologists are still using old testing methods which will not capture those people who have better than severe-to-profound hearing loss and could potentially benefit from cochlear implants," she said. "This lack of knowledge of new criteria likely plays a large role in the under-utilization of this technology."

Another potential hurdle is there are no clear guidelines for how to best test patients. The testing should go well beyond what a person's hearing looks like on paper, and should include assessing quality-of-life factors, the patient's access and willingness to participate in rehabilitation exercises, and a patient's cognitive state, according to Dr. Prentiss.

"We've seen that age alone is no longer a contraindication for cochlear implants. We have to be able to capture these people that have progressive hearing loss and are not doing well with hearing aids. Those patients may not have access to the technology because a lot of providers don't realize that you can have quite a bit of hearing and still benefit from a cochlear implant," she said.

The message to physicians who encounter patients complaining of hearing loss is to refer them for a cochlear implant evaluation, according to Dr. Prentiss.

"If you have a patient who is really struggling and his or her quality of life is going down because of hearing loss, it's never a bad thing to refer that patient to get a cochlear implant evaluation. At least if they are referred, we can get an idea of how they are performing in noise and their overall quality of life. If they don't meet candidacy criteria then maybe we have a baseline and can look for other options that might help them."

Other solutions to the problem include developing clear guidelines for cochlear implant evaluations, as well as educating providers, including audiologists, about current best practices for determining if patients are candidates.

"I'm writing a paper with the support of the American Cochlear Implant Alliance, the largest national organization for cochlear implants, in an effort to inform hearing health care professionals what cochlear implant candidacy looks like today and when it may be appropriate to refer for an evaluation," Dr. Prentiss said.

This national survey is a step toward identifying the eye-opening variability in preoperative assessment practices for evaluating and managing adults with hearing loss in the U.S. The ambiguity, according to Dr. Prentiss, highlights the potential risks for health care inequities, including access to care.

Credit: 
University of Miami Miller School of Medicine

Herpes's Achilles heel

The herpes simplex virus, commonly known as the cold sore virus, is a devious microbe.

It enters the body through regions lined with mucous membranes--mouth, nose and genitals--but quickly establishes lifelong viral hideouts inside nerve cells. After initial infection, the virus lurks dormant only to be reawakened periodically to cause outbreaks marked by the eruption of cold sores or blisters. In a handful of people, the consequences of viral reawaking can be devastating, including blindness and brain inflammation.

Antiviral medications can prevent recurrent outbreaks, but they are not always effective, so for decades, researchers have sought a solution that would quiet the virus for good.

Now, using human fibroblast cells infected with herpes simplex virus (HSV), researchers at Harvard Medical School have successfully used CRISPR-Cas9 gene editing to disrupt not only actively replicating virus but also the far-harder to reach dormant pools of the virus, demonstrating a possible strategy for achieving permanent viral control.

The team's findings are described Dec. 2 in eLife.

"This is an exciting first step--one that suggests it is possible to permanently silence lifelong infections--but much more work remains to be done," said study lead investigator David Knipe, the Higgins Professor of Microbiology and Molecular Genetics in the Blavatnik Institute at Harvard Medical School.

Notably, the research represents the first successful instance of disrupting latent viral reservoirs through gene editing. Latent reservoirs are notoriously impervious to antiviral medications and have also proven hard to gene-edit.

The experiments also identify the mechanisms by which actively replicating virus becomes uniquely vulnerable to gene editing. These very mechanisms may also explain why latent forms of the virus are less amenable to this technique.

Specifically, the experiments reveal that the DNA of an actively replicating virus is more exposed to the Cas9 enzyme--the molecular scissors in the CRISPR-Cas9 gene-editing system. This is because actively replicating viruses have fewer protective histones that wrap around their DNA to shield it.

"The absence of protective histones makes the DNA more accessible and easier to cut, so it's essentially identified HSV's Achilles heel," Knipe said.

The new findings offer a model system for using gene editing in a localized way to disrupt active replication in specific sites. However, Knipe cautions, the arch-challenge of delivering gene-editing therapy to neurons--where the virus hides and enters a state of dormancy--remains to be solved, Knipe added.

More than two-thirds of the world population harbors the virus according to the World Health Organization. While most infections are asymptomatic, in a handful of people HSV can cause serious damage. It can infect the eyes, a condition known as herpes keratitis, and lead to blindness. In people with compromised immune systems, HSV can cause brain inflammation. In newborns, the virus can cause disseminated, systemic disease and brain inflammation and can be fatal in a quarter of infected babies.

Thus, one early therapeutic use of this technique could involve local and limited gene-editing of the epithelial cells in the mouth, eyes or genitals of people with established HSV infections as a way to prevent the virus from causing active outbreaks at vulnerable sites, Knipe said.

"If you want to prevent corneal infections, for example, you might be able to use CRISPR-Cas9 editing in the corneal cells to prevent new infections or prevent the virus from reactivating or reduce the reactivation," Knipe said. "People who have recurrent herpes keratitis infection of the cornea start to go blind after a while because of the reactivation and the resulting inflammation that causes clouding of the cornea."

The advantage of limited, localized gene-editing is avoiding the widespread, possible off-target effects that might inadvertently alter the DNA of cells other than those intended.

"We still have a long way to go in ensuring hyperprecision and safety of new gene-editing tools so local editing could offer a safer, more limited first step," Knipe said.

Credit: 
Harvard Medical School

Novel e-skin achieves self-powered hippocampal neural stimulation

image: This is the e-skin fabrication process.

Image: 
ZHAN Yang

Chinese scientists recently developed a flexible electronic skin (e-skin) capable of self-powered neural stimulation and inducing a neural response. The technology will be useful in characterizing synaptic plasticity.

The research was conducted by Dr. ZHAN Yang's group from the Shenzhen Institutes of Advanced Technology (SIAT) of the Chinese Academy of Sciences, in collaboration with Drs. XUE Xinyu and ZHANG Yan from the University of Electronic Science and Technology.

Synaptic plasticity is one of the main neural mechanisms underlying learning and memory in organisms. Long-term memory requires modification of the synaptic strength between neurons.
Traditionally, electrical neural-stimulation techniques for characterizing synaptic plasticity required an external power source and steer-by-wire system. To overcome these limitations, the researchers proposed a novel self-powered, neural-stimulating e-skin for in vivo characterization of synaptic plasticity.

Composed of flexible photosensitive triboelectric units, the e-skin can be driven by various slight body motions and is wirelessly controlled by photo illumination.
Dr. Zhan said photo illumination can influence the electrical neural-stimulation signals of the e-skin. "Thus the electrical neural-stimulation process on the mouse brain area can be controlled by illumination," he said.

The scientists implanted an electrode to record the fEPSP (field excitatory postsynaptic potential) in the CA1 of the mouse hippocampus as well as a stimulating electrode in the CA3 area. A record of mouse brain activity confirmed the effectiveness of e-skin neural stimulation.

This work demonstrates that the self-powered e-skin has potential applications in the quantification of neural plasticity changes. It could also be applied in novel multifunctional, battery-free and wireless-controlled neural-stimulation systems, as well as in sensory substitution or brain-machine interfaces.

Credit: 
Chinese Academy of Sciences Headquarters

SMART and NTU researchers design polymer that can kill drug-resistant bacteria

image: The co-beta peptide treatment is shown to eradicate biofilm bacteria such as MRSA, a particularly difficult form of bacteria to treat.

Image: 
Singapore-MIT Alliance for Research and Technology (SMART)

Singapore, 12 December 2019 - Researchers from Singapore-MIT Alliance for Research and Technology (SMART), MIT's research enterprise in Singapore, and Nanyang Technological University (NTU) have designed an antimicrobial polymer that can kill bacteria resistant to commonly used antibiotics, including the superbug Methicillin-resistant Staphylococcus aureus (MRSA). The breakthrough can pave the way for the development of medicine to which bacteria have a significantly slower rate of developing resistance, and help prevent hundreds of thousands of deaths each year caused by drug-resistant bacteria.

The new polymer is explained in a paper titled "Enantiomeric glycosylated cationic block co-beta-peptides eradicate Staphylococcus aureus biofilms and antibiotic-tolerant persisters" published last month in leading science journal Nature Communications. It was jointly published by a group of scientists at NTU and AMR, and led by Dr Mary Chan-Park, SMART AMR Principal Investigator and Professor at NTU's School of Chemical and Biomedical Engineering, and Dr Kevin Pethe, Associate Professor at the Lee Kong Chian School of Medicine at NTU. AMR, the Antimicrobial Resistance Interdisciplinary Research Group (IRG) is a part of SMART, MIT's research enterprise in Singapore. SMART is funded by the National Research Foundation of Singapore (NRF) and the Campus for Research Excellence and Technological Enterprise (CREATE) to identify and conduct research on critical problems of societal significance. The AMR IRG is a unique translational research and entrepreneurship program that aims to solve the growing threat of resistance to antimicrobial drugs.

Increasing resistance to antimicrobial medicine is a cause for serious concern with at least 700,000 deaths each year caused by drug-resistant infections and diseases, according to a recent World Health Organisation report. In the United States alone, there is an antibiotic resistant infection acquired every 11 seconds, while a related death occurs every 15 minutes. While alpha-peptides have long been used to treat resistant bacteria such as MRSA, they tend to be rather unstable or toxic in the body. So for the first time, NTU and SMART researchers tested the use of beta-peptides to fight such bacteria in living beings. Designed for stability, the innovative new polymer degrades slowly in the body, giving it more time to work. Importantly, it has little to no toxicity impact.

"Typically, antibiotics don't work on various forms of bacteria like biofilm and persistent bacteria as they become resistant," said Chan-Park. "We are therefore really excited that our new beta-peptide polymer has shown great promise in combating existing antibiotic-resistant strains of bacteria. Further, it has also proven its lethality against biofilm and persistent types of bacteria, which current antibiotics have limited action upon."

Innovative medical research like the new co-beta-peptide is a crucial step towards preventing the staggering number of deaths from persistent and resistant bacteria. AMR also has plans to test the use of this polymer for curing MRSA-affected livestock. This is a growing issue globally, with up to 50% of pig herds in parts of Europe affected by the virus. The new drug will be particularly beneficial to farm workers as the virus has been detected in 20-80% of workers in MRSA-positive herds.

While the next step for the research is to test the polymer on animals infected by MRSA in pig farms, the researchers are also preparing to have the drugs tested in clinical trials for use for the public.

"This is a promising new approach to combating antimicrobial resistance that hasn't been done before," said Pethe. "The toxicity and proof-of-concept studies have shown that this can be on the drug development pathway as it shows good potency and low toxicity and we look forward to having this developed as a topical drug for humans."

Currently, AMR is looking for potential partners for further development of the antimicrobial polymers, particularly for human use.

Credit: 
Singapore-MIT Alliance for Research and Technology (SMART)

Russian scientists studied the effect of selenium on the properties of basil

image: Today many agricultural plants are grown using hydroponics, i.e. in artificial soilless environments. The source of nutrients for the plants is a special substrate surrounding their roots. Thanks to this method agriculturists can harvest the plants all year round and control and adjust the conditions of cultivation.

Image: 
Immanuel Kant Baltic Federal University

Today many agricultural plants are grown using hydroponics, i.e. in artificial soilless environments. The source of nutrients for the plants is a special substrate surrounding their roots. Thanks to this method agriculturists can harvest the plants all year round and control and adjust the conditions of cultivation. One of such conditions is the ratio of micro- and macroelements in the substrate. Any changes in its composition may affect the metabolism and levels of biologically active substances that determine the nutritional qualities of plants.

"In a human body selenium deficiency can cause cardiovascular and endocrine diseases, but the information about its influence on plants remains quite discrepant. This is not an essential microelement for plants, however, many studies show that adding small doses of selenium to fertilizers or substrates (in case of hydroponic cultivation) has a positive effect on the growth and development of plants. Moreover, selenium is known to affect metabolism making plants intensively accumulate biologically active substances of different nature," said Liubov Skrypnik, a Candidate of Biology, and an associate professor at the Institute of Living Systems, Immanuel Kant Baltic Federal University.

The subject of the research was Ocimum basilicum L. or sweet basil -- a plant known all over the world for its pleasant flavor and aroma. It also possesses antibacterial and anti-inflammatory properties and has traditionally been used to treat headache, cough, diarrhea, and kidney malfunction. The healing properties of basil are determined by numerous chemical compounds contained in it. Its leaves are rich in phenolic and hydroxycinnamic acids that make it an excellent antioxidant. Essential oils and vitamins play an important role in the use of basil in the food industry. Moreover, unlike many other plans, basil does not accumulate selenium in excessive concentrations that may cause toxic effects.

The experiment showed that the optimal concentration of selenium is 5 μM when added to hydroponic substrate and 10 μM in a solution used by foliar treatment. This concentration is safe for the plant and at the same time leads to the increase of essential oils, hydroxycinnamic acids, phenolic compounds, and antioxidant levels making basil tastier, healthier, and more fragrant.

Credit: 
Immanuel Kant Baltic Federal University

Speech could be older than we thought

image: Baboons raised in semi-liberty produce about ten vocalizations, associated with different ethological situations, that may be considered as proto-vowels, at the dawn of the emergence of speech.

Image: 
Laboratoire de Psychologie Cognitive (CNRS/Aix-Marseille Université)

For 50 years, the theory of the "descended larynx" has stated that before speech can emerge, the larynx must be in a low position to produce differentiated vowels. Monkeys, which have a vocal tract anatomy that resembles that of humans in the essential articulators (tongue, jaw, lips) but with a higher larynx, could not produce differentiated vocalizations. Researchers at the CNRS and the Université Grenoble Alpes, in collaboration with French, Canadian and US teams, show in a 11 December 2019 review article in Science Advances that monkeys produce well differentiated proto-vowels. The production of differentiated vocalizations is not therefore a question of anatomical variants but of control of articulators. This work leads us to think that speech could have emerged before the 200,000 years ago that linguists currently assert.

Since speech can be considered as being the cornerstone of the human species, it is not surprising that two pairs of researchers, in the 1930s-1950s, had tested the possibility of teaching a home-raised chimpanzee to speak, at the same time and under the same conditions as their baby. All their experiments ended in failure. To explain this result, in 1969 in a long series of articles a US researcher, Philip Lieberman, proposed the theory of the descended larynx (TDL). By comparing the human vocal tract to monkeys, this researcher has shown that these have a small pharynx, related to the high position of their larynx, whereas in humans, the larynx is lower. This anatomic block reportedly prevents differentiated vowel production, which is present in all the world's languages and necessary for spoken language. Despite some criticisms and many acoustic observations that contradict the TDL, it would come to be accepted by most primatologists.

More recently, articles on monkeys' articulatory capacities have shown that they may have used a system of proto-vowels[1]. Considering the acoustic cavities formed by the tongue, jaw and lips (identical in primates and humans), they showed that production of differentiated vocalizations is not a question of anatomy but relates to control of articulators. The data used to establish the TDL came in fact from cadavers, so they could not reveal control of this nature.

This analysis, conducted by pluridisciplinary specialists in the GIPSA-Lab (CNRS/Université Grenoble Alpes/Grenoble INP), in collaboration with the Laboratoire de Psychologie Cognitive (CNRS/Aix-Marseille Université), the University of Alabama (USA), the Laboratoire d'Anatomie de l'Université de Montpellier, the Laboratoire de Phonétique de l'Université du Québec (Canada), CRBLM in Montréal (Canada) and the Laboratoire Histoire Naturelle de l'Homme Préhistorique (CNRS/Muséum National d'Histoire Naturelle /UPVD), opens new perspectives: if the emergence of articulated speech is no longer dependent on the descent of the larynx, which took place about 200,000 years ago, scientists can now envisage much earlier speech emergence, as far back as at least 20 million years, a time when our common ancestor with monkeys lived, who already presumably had the capacity to produce contrasted vocalizations.

Credit: 
CNRS

Martian aurora offers climate change clues, Embry-Riddle reports

image: Physics Professor Dr. Edwin Mierkiewicz and Ph.D. candidate Andréa Hughes of Embry-Riddle Aeronautical University recently helped release new information about a common type of dayside aurora on Mars.

Image: 
Embry-Riddle/Daryl LaBello

SAN FRANCISCO, Calif. - A newly published study, presented on Dec. 12 at the American Geophysical Union (AGU) meeting, reveals that a type of Martian aurora originally detected by NASA's MAVEN spacecraft is in fact the most common aurora on the Red Planet, Embry-Riddle Aeronautical University researchers said.

The study, co-authored by scientists at the University of Colorado Boulder's Laboratory for Atmospheric and Space Physics (LASP) and funded by the MAVEN (Mars Atmosphere and Volatile EvolutioN) mission, also suggests a way to track water loss and better understand how the Martian climate has changed over time, the team reported.

Unlike the brilliantly colored auroras that dance across the night sky near the Earth's polar regions, the most common aurora on Mars is a dayside phenomenon called a proton aurora, explained Embry-Riddle Ph.D. candidate Andréa Hughes, lead author of a paper scheduled to be published Dec. 12 in the Journal of Geophysical Research, Space Physics.

Proton auroras on Mars form when the solar wind streams toward the massive hydrogen cloud that encases Mars, and positively charged protons get neutralized by grabbing electrons from hydrogen atoms. When those energetic, fast-moving atoms interact with molecules in the lower atmosphere, they emit ultraviolet light, creating a proton aurora, said Hughes.

"Observations of proton auroras at Mars provide a unique perspective of hydrogen and, therefore, water loss from the planet," co-author Dr. Edwin Mierkiewicz of Embry-Riddle said. "Through this research, we can gain a deeper understanding of the sun's interactions with the upper atmosphere of Mars and with similar bodies in our (solar system), or in another solar system, that lack a global magnetic field."

The researchers found that proton auroras on Mars were more frequent and intense when levels of hydrogen escaping into the atmosphere were highest. In addition, co-author Mike Chaffin of the University of Colorado Boulder said, "the team spotted many more proton auroras on the dayside of Mars during the hot, dusty southern summer season, when the planet is closer to the sun." Proton auroras were spotted in 14 percent of all dayside observations in the dataset, and in more than 80 percent of dayside southern summer observations.

Swirling dust and higher temperatures during the Martian southern summer cause water vapor to be lofted to high altitudes, where the sun's extreme ultraviolet light can split the water into hydrogen and oxygen. Because hydrogen is lightweight, it filters to the top of the Martian atmosphere and enriches the planet's surrounding hydrogen cloud, or corona. This "puffed up" hydrogen corona can more easily escape the planet and interact with incoming solar wind protons, producing more proton auroras during this season.

Thus, proton auroras "can actually be used as a proxy for what's happening in the hydrogen corona surrounding Mars, and therefore, a proxy for times of increased atmospheric escape and water loss," said Hughes.

Although Martian proton auroras can't be seen by human eyes, detection was no problem for the Imaging UltraViolet Spectrograph (IUVS) instrument on NASA's MAVEN spacecraft. The study leveraged MAVEN/IUVS data encompassing multiple Martian years.

When MAVEN first detected proton auroras in 2016, researchers thought that such events were "rather rare because we weren't looking at the right times and places," Chaffin said. In subsequent investigations, however, the scientists confirmed that proton auroras are highly common on Mars. "By comparison," said Dr. Nick Schneider, study coauthor and lead of the IUVS team at LASP, "the two other types of Martian auroras that are more similar to the nighttime events on Earth - discrete and diffuse auroras - are rarely observed on Mars."

The goal of NASA's MAVEN mission, launched in November 2013, is to learn how Mars lost most of its atmosphere and water and turned into a cold, dry, inhospitable planet. MAVEN's principal investigator is based at the University of Colorado / LASP and the MAVEN project is managed by NASA's Goddard Space Flight Center.

Hughes is a Ph.D. candidate who is pursuing a doctorate degree in Engineering Physics from Embry-Riddle. She hopes to one day work for NASA as part of the team that sends the first humans to Mars.

"Perhaps one day, when interplanetary travel becomes commonplace, travelers arriving at Mars during southern summer will have front-row seats to observe Martian proton auroras majestically dancing across the dayside of the planet (while wearing ultraviolet-sensitive goggles, of course)," she said. "These travelers will witness firsthand the final stages of Mars losing the remainder of its water to space."

Credit: 
Embry-Riddle Aeronautical University

Scandinavians' little linguistic hat trick

Linguist Dave Kush at the Norwegian University of Science and Technology's Department of Language and Literature has been studying a phenomenon in which Norwegian, Swedish and Danish stand out.

This language peculiarity has to do with the order of words, or the syntax. The basic point of the study is to better understand the grammatical building blocks in our brain.

Moving the most important word to the beginning of a sentence is called topicalization. The first word acts as a "heading" for the rest of the sentence.

"Other languages also use topicalization, but the Scandinavians have developed topicalization into an art. The keyword can be retrieved from a relative clause and placed at beginning of the sentence, even when the context is a distance away. The connection - the interpretation of the first word - comes later in the sentence," says Dave Kush.

Sometimes topicalization works in both Norwegian and English, for example in the phrase "Han har ikke spist den kaka," starting with the subject "He." We can make the cake (object) the main point by moving the word to the beginning: "Den kaka har han ikke spist."

Here's exactly the same sentences as above in English: "He hasn't eaten that cake" can be switched to "That cake, he hasn't eaten," to indicate that exactly that one cake was not eaten.

But most of the time this only works in the Scandinavian languages. The phrase "Kaker lurer han på om Kari lager" (literally: Cakes he wonders if Kari is making.) works just fine in Norwegian. We also understand what is meant when the question word is moved first: "Hva lurer han på om Kari lager?" (literally: What is he wondering if Kari is making?)

For Norwegians it also makes sense to say something like this: "Bakdøren blir han nervøs om de lar stå ulåst" (literally: The back door he is nervous whether they leave unlocked).

"None of these sentences is viable in English. They would be perceived as wrong, and perhaps even incomprehensible," says Kush.

And not just in English. Kush and his colleagues have investigated the research that has been done on a variety of languages, including Japanese, Italian and Arabic. Their findings indicate that the Scandinavian languages ??stand alone in being able to use topicalization so flexibly.

Icelandic does not have this language feature either, so this "invention" probably evolved after Old Norse fell out of use in Norway.

Norwegian speakers can move the object, question words and almost any sentence element to the front of the sentence and still understand the meaning. This works even if there is a great distance between the first word and what comes later in the sentence to give us the context for the meaning.

"But we can't move the words around any which way. In a lot of cases, it works, but in others it doesn't at all," Kush says.

If we put a question word first in the sentence: "Han blir nervøs om Sigrid baker boller" (literally: He gets nervous if Sigrid bakes buns), it's too much even for Scandinavians. The phrase " Hva blir han nervøs om Sigrid lager?" (literally: What does he get nervous about if Sigrid bakes?) is not accepted as passable Norwegian. The sentence doesn't work.

No written grammatical rules exist for which parts of speech or sentences can be moved and when. The researchers figure out what is possible or not by testing sentences on a variety of subjects. Although young and old choose different words, Kush did not find any difference between the generations in how they construct the sentences.

Kush doesn't have an opinion on whether or not it iIs it advantageous to be able to emphasize a word through moving it.

"Why this language feature developed, we don't know. Maybe it just happened by chance," Kush says.

"Can this be perceived as the Scandinavian languages being under pressure and that their word order lacks organization?"

"No, all languages have built-in, complicated rules that determine what's possible and what isn't, particularly Norwegian," he says.

In linguistics, it has been common to assume that universal boundaries exist for changing word order. But that is not the case.

Already in the 1980s it was reported that the Scandinavian languages llow radical changes in word order far more often than other languages do.

Kush has confirmed that this is the case through scientific experiments with representative samples of people and has identified what people perceive as acceptable Norwegian - and what they don't.

NTNU colleague Terje Lohndal and Jonathan Sprouse at the University of Connecticut collaborated with Kush to publish an article on Scandinavian topicalization in the autumn issue of Language, a leading journal of linguistic research.

To find out more about this Scandinavian language peculiarity, Kush and his colleagues plan to study how children learn which sentences are allowable and which are not. Researchers will use machine learning to simulate the children's learning on computers.

Credit: 
Norwegian University of Science and Technology

Daylight saving time does not misalign human cycles

image: Four clocks with 24h analog dial signaling latitude , the efficiency of noon insolation in summer, the permanent daytime (yellow), the permanent night time (red) and the alternating region (pink). Human activity starts between the winter sunrise (w) and the equinoctial sunrise 6am. DST regulations bring human activity one hour earlier in the spring transition: from w to w1, or from w1 to w2, or from w2 to w3. Clocks display mean solar time.

Image: 
Universidad de Sevilla

Professor José María Martín-Olalla, from the University of Seville, has published a new report where the impact of seasonal clock-changing in daily life is analyzed from time use surveys in United States, Spain, Italy, France and Great Britain. These countries have faced seasonal regulation of clocks for more than forty years. The results state that human cycles are not misaligned by Daylight Saving Time regulations. The report also shows the impact of latitude in the seasonal adaptation of human cycles, jeopardizing the current position of the European Commission which pushes for a unique regulation in the European Union

The report was released this month by Scientfic Reports (an open-access peer-reviewed scientific journal from Springer Nature Publishing group) in the Collection Social Physics and focuses in the seasonal deviations of the sleep/wake cycle and of the labor cycle. None of these human cycles is found to exhibit significant seasonal deviations in week days. This is a major, unnoticed outcome of the seasonal regulation of clocks. After continued, predictable seasonal clock changing arrangements virtually nobody delays their activity in summer or advances it in winter, signaling the acceptance of the practice in modern societies. That way the seasonal clock arrangements promote stable year-round social timing and, at the same time, a seasonal adaptation of human activity, which advances in spring-summer, when daytime is the longest, and delays in autumn-winter, when daytime is the shortest.

The sleep/wake cycle in week ends, when free preferences are most frequent, shows a distinct pattern. Bedtimes delay in summer, following the delay in sunset times, a behaviour that plays against the regulation of clocks, which advanced them after the spring transition. Nonetheless, wake-up times advance in summer, also following the advance in sunrise times. This behaviour now amplifies the advance of clock time after the spring transition. Overall the best explanation for these opposite findings is that human cycles are not misaligned by the size and direction of DST regulations, as they still track sunrises and sunsets. Lack of misalignment explains the success of DST regulations in modern societies.

Summer time arrangements in Europe

The report also shows the impact of latitude in the seasonal adaptation of human cycles, an issue of the utmost importance in Europe. Human cycles in low latitude countries (USA, ESP and ITA) exhibit larger and more frequent seasonal deviations than those at higher latitudes (FRA and GBR), despite the light and dark cycle displays larger seasonality in the latter case. Martín-Olalla explains this paradox saying that above a circle of latitude, solar deviations are large enough and fast enough so that human cycles are less able to track them accurately. There, clock time plays the leading synchronizing role and, eventually, gives rise to a preference for discontinuing DST regulations which part ways with the seasonal regulation of human activity. The current wave of DST discussions is promoted by this fact in Northern countries like Finland.

On the contrary, below that circle of latitude solar seasonality is smaller but has a greater impact on human cycles, which exhibit fine tuning with solar activity. At this range, societies find in DST regulations a convenient, effective way of promoting circannual human cycles adapted to seasons. The practice helps to keep the sunrise as a lodestar for the start of human activity; helps to avoid exposition to noon insolation and overheating, an important issue in the Tropics (it should be stressed that below the 47th circle of latitude, the latitude of Switzerland and Lake Superior, noon insolation is characteristically tropical in summer). Finally it helps both lark people (those with propensity to morning activity) and owl people (those with propensity to evening activity) get timely activated through seasons: not too late and not too early.

The impact of latitude jeopardizes the current position of the European Commission which pushes for a unique regulation in the European Union. However the Union exhibits vividly different seasonal variations in the light and dark cycle. They range from a 98% noon insolation efficiency in summer at the 35th circle of latitude (Malta, Chipre) with less than 3h of spread in sunrise times to a 24h spread of sunrise times at the 70th circle of latitude (Finland Lapland), where seasonal clock changing is virtually meaningless. Therefore the report urges the European Commission to rethink its position and allow opts-out on this issue which would stratify with latitude as in Australia, Chile and Brazil. A video posted in youtube also describes the problem faced by the European Commission.

This is the third manuscript authored by Martín-Olalla analyzing basic human activity and the impact of latitude. Previously a report forward the synchronizing role of the winter day, and a second report, described seasonal synchronizing patterns in industrial and pre-industrial societies from the Equator to the 55th circle of latitude. Both manuscripts were also published in Scientific Reports.

Credit: 
University of Seville

The danger behind certain biologics

image: Dendritic cells have their own form of program memory that hinges on a well-known immune signaling molecule called TNFalpha.

Image: 
Stephanie King

Autoimmune disorders such as rheumatoid arthritis, psoriasis, and Crohn's disease plague tens of millions of Americans and are the result of the body's immune system, whose role is to fight against disease-causing pathogens, turning against itself.

Thankfully, several new drugs designed to fight these diseases are now available. The downside--the drugs, a class of biologics called TNF inhibitors, carry a risk of serious infections and even cancer.

A research team led by Michigan Medicine may have discovered why. Their study, which appears in the journal Science Advances, reveals a previously unknown function of a specific type of immune cell called dendritic cells.

"Dendritic cells are the master orchestrator of the immune response, telling the other cells of the immune system what to do," explains Michal Olszewski, DVM, Ph.D., a research biologist with the Ann Arbor VA Hospital, associate professor of internal medicine at U-M and senior author on the paper.

Dendritic cells are part of the innate immune network, the body's first line of defense against a threat. They help another type of immune cell called T cells, which are part of the adaptive immune system, learn how to respond appropriately to a given germ or disease-causing agent.

This study reveals that the cells have their own form of program memory and hinges on a well-known immune signaling molecule called TNFalpha, which causes the inflammation so painfully familiar to those with arthritis and other autoimmune diseases.

"Our studies have found that TNFalpha is part of the system that programs dendritic cells so that they know how to program T cells," says Olszewski.

TNFalpha is especially important in helping dendritic cells teach T cells to fight off infections like certain fungal infections and tuberculosis that can hide inside the body's cells. This is why people taking these autoimmune drugs are particularly at risk.

"Some microbes are very clever and fool the immune system so it doesn't detect and kill them, causing disease. But in our study, we found in the presence of TNFalpha, microbes can't do those tricks. With its help, dendritic cells don't get fooled and therefore can activate the protective T cell response," says co-first author Jintao Xu, Ph.D. of the Ann Arbor VA Hospital.

Furthermore, the group found that the dendritic cell programming relied on rapidly developing epigenetic changes affording dendritic cell program stability and conferred to the T cells. This finding has major implications for the development of therapies targeting the immune system.

"This will be important for vaccine development, for understanding how the immune system responds to chronic infections, and why people who take anti-TNF for treatment of autoimmune diseases are particularly vulnerable to these kinds of diseases," comments Olszewski.

In an additional proof-of-concept study, the team found that by removing dendritic cells from mice taking an anti-TNF drug, exposing the cells to TNFalpha and reinjecting them into the mice, they could induce a normal immune response against infection.

This procedure hints at a complimentary therapy for people on anti-TNF drugs as well as a potential advanced immunotherapy for cancer. "Cancer can produce a group of signals that dampen the immune response. We speculate that one could program the dendritic cells outside of the cancerous environment and make them remember that they are to remain activated and continue to fight the cancer instead of ignoring it," says Olszewski.

Credit: 
Michigan Medicine - University of Michigan

Newfound Martian aurora actually the most common; sheds light on Mars' changing climate

image: Conceptual image depicting the early Martian environment (right) -- believed to contain liquid water and a thicker atmosphere -- versus the cold, dry environment seen at Mars today (left).

Image: 
NASA's Goddard Space Flight Center

A type of Martian aurora first identified by NASA's MAVEN spacecraft in 2016 is actually the most common form of aurora occurring on the Red Planet, according to new results from the mission. The aurora is known as a proton aurora and can help scientists track water loss from Mars' atmosphere.

At Earth, aurora are commonly seen as colorful displays of light in the night sky near the polar regions, where they are also known as the northern and southern lights. However, the proton aurora on Mars happens during the day and gives off ultraviolet light, so it is invisible to the human eye but detectable to the Imaging UltraViolet Spectrograph (IUVS) instrument on the MAVEN (Mars Atmosphere and Volatile EvolutioN) spacecraft.

MAVEN's mission is to investigate how the Red Planet lost much of its atmosphere and water, transforming its climate from one that might have supported life to one that is cold, dry, and inhospitable. Since the proton aurora is generated indirectly by hydrogen derived from Martian water that's in the process of being lost to space, this aurora could be used to help track ongoing Martian water loss.

"In this new study using MAVEN/IUVS data from multiple Mars years, the team has found that periods of increased atmospheric escape correspond with increases in proton aurora occurrence and intensity," said Andréa Hughes of Embry-Riddle Aeronautical University in Daytona Beach, Florida. Hughes is lead author of a paper on this research published December 12 in the Journal of Geophysical Research, Space Physics. "Perhaps one day, when interplanetary travel becomes commonplace, travelers arriving at Mars during southern summer will have front-row seats to observe Martian proton aurora majestically dancing across the dayside of the planet (while wearing ultraviolet-sensitive goggles, of course). These travelers will witness firsthand the final stages of Mars losing the remainder of its water to space." Hughes is presenting the research on December 12 at the American Geophysical Union meeting in San Francisco.

Different phenomena produce different kinds of aurora. However, all aurora at Earth and Mars are powered by solar activity, whether it be explosions of high-speed particles known as solar storms, eruptions of gas and magnetic fields known as coronal mass ejections, or gusts in the solar wind, a stream of electrically conducting gas that blows continuously into space at around a million miles per hour. For example, the northern and southern lights at Earth happen when violent solar activity disturbs Earth's magnetosphere, causing high velocity electrons to slam into gas particles in Earth's nightside upper atmosphere and make them glow. Similar processes generate Mars' discrete and diffuse aurora - two types of aurora that were previously observed on the Martian nightside.

Proton aurora form when solar wind protons (which are hydrogen atoms stripped of their lone electrons by intense heat) interact with the upper atmosphere on the dayside of Mars. As they approach Mars, the protons coming in with the solar wind transform into neutral atoms by stealing electrons from hydrogen atoms in the outer edge of the Martian hydrogen corona, a huge cloud of hydrogen surrounding the planet. When those high-speed incoming atoms hit the atmosphere, some of their energy is emitted as ultraviolet light.

When the MAVEN team first observed the proton aurora, they thought it was a relatively unusual occurrence. "At first, we believed that these events were rather rare because we weren't looking at the right times and places," said Mike Chaffin, research scientist at the University of Colorado Boulder's Laboratory for Atmospheric and Space Physics (LASP) and second author of the study. "But after a closer look, we found that proton aurora are occurring far more often in dayside southern summer observations than we initially expected." The team has found proton aurora in about 14 percent of their dayside observations, which increases to more than 80 percent of the time when only dayside southern summer observations are considered. "By comparison, IUVS has detected diffuse aurora on Mars in a few percent of orbits with favorable geometry, and discrete aurora detections are rarer still in the dataset," said Nick Schneider, coauthor and lead of the IUVS team at LASP.

The correlation with the southern summer gave a clue as to why proton aurora are so common and how they could be used to track water loss. During southern summer on Mars, the planet is also near its closest distance to the Sun in its orbit and huge dust storms can occur. Summer warming and dust activity appear to cause proton auroras by forcing water vapor high in the atmosphere. Solar extreme ultraviolet light breaks the water into its components, hydrogen and oxygen. The light hydrogen is weakly bound by Mars' gravity and enhances the hydrogen corona surrounding Mars, increasing hydrogen loss to space. More hydrogen in the corona makes interactions with solar-wind protons more common, making proton aurora more frequent and brighter.

"All the conditions necessary to create Martian proton aurora (e.g., solar wind protons, an extended hydrogen atmosphere, and the absence of a global dipole magnetic field) are more commonly available at Mars than those needed to create other types of aurora," said Hughes. "Also, the connection between MAVEN's observations of increased atmospheric escape and increases in proton aurora frequency and intensity means that proton aurora can actually be used as a proxy for what's happening in the hydrogen corona surrounding Mars, and therefore, a proxy for times of increased atmospheric escape and water loss."

This research was funded by the MAVEN mission. MAVEN's principal investigator is based at the University of Colorado's Laboratory for Atmospheric and Space Physics in Boulder, Colorado, and NASA Goddard manages the MAVEN project. NASA is exploring our Solar System and beyond, uncovering worlds, stars, and cosmic mysteries near and far with our powerful fleet of space and ground-based missions.

Credit: 
NASA/Goddard Space Flight Center

How can you help your organization's expatriates succeed?

image: Official logo for the Society for Industrial and Organizational Psychology

Image: 
SIOP

Bowling Green, Ohio December 12, 2019 - SIOP publishes white paper that explores how to promote your overseas workers' productivity and well-being.

The SIOP White Paper series organizes and summarizes important and timely topics in I-O psychology. The newest white paper, "Culture and Overseas Work: Expectations, Preparations, Coping; Return," focuses on the well-being of expatriates.

The term sojourners is broad and includes all kinds of overseas experiences, including work, study, migration, diplomacy, proselytizing, and tourism. Expatriates, the main focus of this paper, often categorized as corporate or self-initiated, the former group sent overseas by an employer, perhaps for several years, whereas the latter moves overseas to seek employment.

Companies send workers overseas with specific business goals that are best met by employees who adjust and perform well. Although it has proven difficult to estimate the prevalence of expat failure, the cost to a company of a failed overseas assignment is high. Expat failure is characterized by some combination of poor performance, lack of adjustment, and early return.

This white paper provides an overview of the experiences and challenges encountered by people who live and work outside of their home societies and introduces some of the solutions currently available to meet these challenges.

This white paper was written by SIOPers William K. Gabrenya and Yumiko Mochinushi. Dr. Gabrenya is a professor of cultural and social psychology at Florida Institute of Technology, USA. His research focuses primarily on culture competence, expatriate/repatriate adjustment, modernization processes, social stratification, and indigenous psychology movement. Dr. Mochinushi is an instructional assistant professor at Texas A&M University, having recently completed her doctorate in I-O psychology at Florida Tech. Her current research focuses on applicant faking on personality assessments and cross-cultural competence.

Read the new white paper on the SIOP website.

Credit: 
Society for Industrial and Organizational Psychology

Short-lived light sources discovered in the sky

image: A source visible in an old plate (left, seen as the bright source at the centre of the square) has disappeared in a later plate (right). From Villarroel et al. (2019).

Image: 
Villarroel et al. (2019)

A project lead by an international team of researchers use publicly available data with images of the sky dating as far back as to the 1950s to try to detect and analyse objects that have disappeared over time. In the project "Vanishing & Appearing Sources during a Century of Observations" (VASCO), they have particularly looked for objects that may have existed in old military sky catalogues from the 1950s, not to be found again in modern sky surveys. Among the physical indicators that they are looking for are stars that have vanished in the Milky Way.

"Finding an actually vanishing star - or a star that appears out of nowhere! - would be a precious discovery and certainly would include new astrophysics beyond the one we know of today", says project leader Beatriz Villarroel, Stockholm University and Instituto de Astrofísica de Canarias, Spain.

When a star dies it either undergoes very slow changes and becomes a white dwarf or it dies with a sudden bright explosion i.e. supernova. A vanishing star can be an example of an "impossible phenomenon" that could be attributed either to new astrophysical phenomena or to extra-terrestrial activity. Indeed, the only non-ETI (extra-terrestrial intelligence) explanation for a vanishing star would be exceedingly rare events called "failed supernovae". A failed supernovae is theoretically predicted to occur when a very massive star collapses into a black hole without any visible explosion. Other physical indicators of ETI activity that the authors are looking for are signs of red interstellar communication lasers and Dyson spheres. A Dyson sphere is a hypothetical giant structure surrounding a star to harness its energy.

"As a by-product, VASCO has the potential to discover rare extremely-variable objects. These can shed light on fast hard-to-observe phases of stellar evolution and active galactic nucleus'", says co-author Sébastien Comerón, Oulu University, Finland.

The researchers have carefully examined about 15% of the 150,000 candidate objects in the available data and found approximately a hundred red transients - very variable objects or events in the sky. Some of these objects appear to have flared up at least ~ 8-9 magnitudes, or several thousand times brighter, in a very short time.

"We are very excited about following up on the 100 red transients we have found", says Beatriz Villarroel.

"But we are clear that none of these events have shown any direct signs of being ETI. We believe that they are natural, if somewhat extreme, astrophysical sources", says Martin López Corredoira, co-author of the paper, Instituto de Astrofísica de Canarias, Spain.

The researchers are now looking for the possibility to arrange a citizen science project, one that is aided by artificial intelligence. In order to be able to examine all the 150,000 candidates that have been identified from the material, they must speed up the process of identifying anomalies in the images.

"We hope to get help from the community to look through the images as a part of a citizen science project. We are looking at ways to do that right now and that will be something we will be able to talk more about at a later date", says Lars Mattsson, Stockholm University.

Credit: 
Stockholm University

Tracking lab-grown tissue with light

image: An empty petri dish with two optical fibers, illustrating one version of the researchers' experiment. The left-hand fiber (usually shining infrared light, but depicted here as visible red light) is a temperature sensor. The top fiber shines green, red or blue light into the petri dish to adjust the signal that the temperature sensor measures.

Image: 
J.L. Lee/NIST

Someday, doctors would like to grow limbs and other body tissue for soldiers who have lost arms in battle, children who need a new heart or liver, and many other people with critical needs. Today, medical professionals can graft cells from a patient, deposit them onto a tissue scaffold, and insert the scaffold into the body to encourage the growth of bone, cartilage and other specialized tissue. But researchers are still working toward building complex organs that can be implanted into patients.

Scientists at the National Institute of Standards and Technology (NIST) are supporting this field of research by developing a promising new kind of light-based sensor to study tissue growth in the lab.

The NIST team's proof-of-concept work, published today in Sensors and Actuators B, demonstrates a small sensor that uses a light-based signal to measure pH, the measurement unit for acidity, an important property in cell-growth studies. The same basic design could be used to measure other qualities such as the presence of calcium, cell growth factor and certain antibodies.

Unlike conventional sensors, this measurement method could be used to monitor the environment in a cell culture long-term -- for weeks at a time -- without having to disturb the cells regularly to calibrate the sensing instruments. Watching properties of the tissue in real time as they slowly change, over days or weeks, could greatly benefit tissue engineering studies to grow teeth, heart tissue, bone tissue and more, said NIST chemist Zeeshan Ahmed.

"We want to make sensors that can be put inside growing tissue to give researchers quantitative information," Ahmed said. "Is the tissue actually growing? Is it healthy? If you grow a bone, does it have the right mechanical properties or is it too weak to support a body?"

The work could have benefits beyond tissue engineering too, into studying the progression of diseases such as cancer.

"What these sensors could give people is real-time information about tissue growth and disease progression," said American University chemist and NIST guest researcher Matthew Hartings. Conventional sensors give researchers a series of snapshots without showing them the path between those points, Hartings said. But photonic sensors could provide scientists with continuous information, the equivalent of a GPS navigation app for disease.

"We want to provide researchers with a detailed map of the incremental changes that happen as tissue either grows in a healthy way or becomes diseased," Hartings said. "Once researchers know the 'streets' a disease is taking, then they can better prevent or support the changes that are happening" in a patient's body.

A Problem to Solve

Measurements of pH are a vital part of tissue engineering studies. As cells grow, their environment naturally becomes more acidic. If the environment becomes too acidic -- or too basic -- the cells will die. Scientists measure pH on a scale from 0 (very acidic) to 14 (very basic), with an ideal environment for most cells in a narrow range around a pH of 7.

Commercial pH instruments are highly accurate but unstable, meaning they require frequent calibrations to ensure accurate readings day to day. Without calibration, these conventional pH meters lose up to 0.1 pH units of accuracy daily. But tissue engineering studies take place on the order of weeks. A culture of stem cells might need to be grown for almost a month before they turn into bone.

"An increment of 0.1 pH is significant," Ahmed said. "If your pH value changes by 1, you kill the cells. If after a few days I can't trust anything about my pH measurement, then I'm not going to use that measurement method."

On the other hand, if researchers disturb the growing cells every time they have to measure the cell culture's pH, then the scientists are introducing another kind of uncertainty to their measurements, since they are altering the cells' environment.

What's needed for this kind of research, Ahmed said, is a measurement system that can stay inside an incubator with the cells in their culture medium and not need to be removed or calibrated for weeks at a time.

Brave New Sensors

For years, Ahmed and his team have been developing photonic sensors, small lightweight devices that use optical signals to measure a range of qualities including temperature, pressure and humidity.

Some of these novel devices use commercially available, flexible optical fibers etched with a Bragg grating, a kind of filter for light that reflects certain wavelengths and allows others to pass. Changes in temperature or pressure alter the wavelengths of light that can pass through the grating.

To adapt their photonic devices to a pH measurement, Ahmed and Hartings relied on a well-known concept in science: When an object absorbs light, the energy absorbed "has to go somewhere," Ahmed said, and in many cases that energy turns into heat.

"For every individual photon, the heat produced is a very small amount of energy," Ahmed said. "But if you have lots of photons coming in, and you have lots of molecules, it becomes an appreciable change in heat."

For their demonstration, the scientists used a substance that changes color in response to changes in pH, a material that many people may remember from biology classes: red cabbage juice powder. Cabbage juice changes its color from shades of dark purple to light pink depending on the acidity of a solution. That change in color can be picked up by Ahmed's photonic temperature sensors.

Researchers filled a petri dish with the cabbage juice solution. One optical fiber was positioned above the dish. It was connected to a laser pointer and shined light into the sample. A second optical fiber was physically embedded in the liquid. This second fiber contained the Bragg grating and acted as the temperature sensor. Ahmed's team controlled the solution's pH manually.

To make a measurement, the researchers shone one color of light -- such as red -- into the sample from above. The cabbage juice absorbed the red light to varying degrees based on its color, which depended on the pH of the solution at that time. The photonic thermometer fiber picked up these slight changes in the juice's heat. A change in temperature changes the wavelengths of light that can pass through the fiber's Bragg grating.

Next, the researchers shone a second color of light -- such as green -- into the liquid, and repeated the process.

By comparing how much heat was generated by each color of light, researchers could determine the exact color of the cabbage juice at that moment, and that told them the pH.

"Literally we said, 'Can we turn two laser pointers on and off for a few minutes and see if we can turn that into a pH meter?'," Ahmed said. "And we were able to show that it works over a wide range," from a pH of 4 to a pH of 9 or 10.

Ongoing work shows the photonic pH measurements are accurate to plus or minus 0.13 pH units and are stable for at least three weeks, much longer than conventional measurements.

Beyond Cabbage Juice

The researchers say that according to their tissue engineering collaborators, the new photonic sensors could provide useful information for a range of biological systems being studied, particularly the growth of heart and bone cells.

For their next round of experiments, already underway, the NIST researchers are using another pH-sensitive dye called phenol red. In addition, they are working to encapsulate the dye in a plastic coating around the fiber itself so that it does not interact with the cell medium. The team is also conducting its first test of the system in a real cell culture, with help from NIST colleagues who specialize in tissue engineering.

Future plans include measuring quantities beyond pH, which would simply require swapping out phenol red for a different dye sensitive to whatever property researchers want to measure.

NIST researchers will also be testing how cell cultures are affected by the slight, temporary temperature changes (about 1-2 kelvin) in localized areas of the sample that occur as a result of this measurement method. Ahmed says that so far, potential collaborators are not overly concerned about the issue of localized heating, and that his team will be working to reduce the temperature changes as much as possible.

And much further in the future, Ahmed hopes the measurement scheme could potentially be used to monitor the growth of tissue in a real person's body.

"The long-term goal is being able to put implantable devices into people where you're trying to grow bones and muscles, and then hopefully over time the sensors could be designed to dissolve away and you wouldn't even have to go back in and remove them," Ahmed said. "That's the ultimate dream. But baby steps first."

EDITOR'S NOTE: This story was updated on the afternoon of December 13, 2019 with an additional paragraph to indicate the temporary temperature changes that result from this technique as well as the researchers' plans to test their effects on cell cultures.

Credit: 
National Institute of Standards and Technology (NIST)