The ability to generate light pulses of sub-​femtosecond duration, first demonstrated some 20 years ago, has given rise to an entirely new field: attosecond science and technology. Table-​top laser systems have emerged that enable studies that for decades were but a distant dream — to follow, image and characterise electronic processes in atoms, molecules and solids on their natural, attosecond timescales. The laser systems that make such studies possible typically operate in the extreme ultraviolet spectral band. There has long been a push to achieve higher photon energies though. Of particular interest is the ‘water window’, occupied by soft x-​ray radiation with wavelengths between 2.2 and 4.4 nm. That spectral window owes its name, and importance, to the fact that at those frequencies, photons are not absorbed by oxygen (and hence by water), but they are by carbon. This is ideal for studying organic molecules and biological specimens in their natural aqueous environment. Today, a handful of attosecond sources spanning this frequency range exist, but their applicability is limited by relatively low repetition rates of 1 kHz or below, which in turn means low count rates and poor signal-​to-noise ratios. Writing in Optica, Justinas Pupeikis and colleagues in the Ultrafast Laser Physics group of Prof. Ursula Keller at the Institute for Quantum Electronics report now an essential leap to overcome the limitations of the prior sources. They present the first soft-​x-ray source that spans the full water window at 100 kHz repetition rate — a hundredfold improvement compared to the state-​of-the-art sources.

A boost in technological capability

The bottleneck in producing soft x-​rays at high repetition rates has been the lack of suitable laser systems to drive the key process underlying attosecond-​pulse generation in table-​top systems. That process is known as high-​harmonic generation, and it involves an intense femtosecond laser pulse interacting with a target, typically an atomic gas. The nonlinear electronic response of the target then causes the emission of attosecond pulses at an odd-​order multiple of the frequency of the driving laser field. To ensure that that response contains x-​ray photons spanning the water-​window range, the femtosecond source has to operate in the mid-​infrared range. Also, it has to deliver high-​peak-power pulses. And all of that at high repetition rates. Such a source did not exist so far.

Pupeikis et al. took up the challenge and systematically improved a layout they had already explored in earlier work, based on optical parametric chirped pulse amplification (or OPCPA for short). They had established before that the approach is promising with a view to realizing high-​power mid-​infrared sources, but substantial improvements were still needed to reach the performance required for the high-​harmonic generation of x-​ray photons in the water window. In particular, they pushed the peak power from previously 6.3 GW to 14.2 GW, and they reached an average power of 25 W for pulses just a bit longer than two oscillations of the underlying optical field (16.5 fs). The peak power demonstrated is comfortably the highest reported to date for any high-​repetition-rate system with a wavelength above 2 μm.

Ready for the x-​ray room

With this level of performance at their disposal, the team was ready for the next stage, frequency upconversion through high-​harmonic generation. For that, the output beam of the OPCPA was routed via a periscope system to another laboratory more than 15 m away, to accommodate for local lab-​space constraints. There, the beam met a helium target, kept at a pressure of 45 bar. Such high pressure was necessary for phase-​matching between the infrared and the x-​ray radiation, and thus optimal energy-​conversion efficiency.

All pieces carefully put in place, the system indeed delivered. It generated coherent soft x-​ray radiation extending to an energy of 620 eV (2 nm wavelength), covering the full water window — a stand-​out achievement relative to other high-​repetition-rate sources in this frequency range. A window of opportunity

This demonstration opens up a vast spectrum of fresh opportunities. Coherent imaging in the water-​window spectral region, highly relevant for chemistry and biology, should be possible with a compact setup. At the same time, the high repetition rate available helps, for instance, addressing the limitations due to space-​charge formation which plague photoemission experiments with pulsed sources. Moreover, the ‘water window’ comprises not only the K-​edges of carbon, nitrogen and oxygen, but also the L- and M-​edges of a range of metals, which can now be studied with higher sensitivity or specificity.

With such bright prospects, the realization of the source now presented heralds the beginning of the next generation of attosecond technology, one where experimentalists for the first time can make combined use of high repetition rates and high photon energies. An attosecond beamline designed to exploit these new capabilities is currently under construction in the Keller lab.

“One of the most important aspects of vision is fast detection of important events, like detecting threats or the opportunity for a reward. Our result shows this depends on visual processing in the midbrain, not only the visual cortex,” said Richard Krauzlis, Ph.D., chief of the Section on Eye Movements and Visual Selection at NEI and senior author of the study.

Visual perception — one’s ability to know that one has seen something — depends on the eye and the brain working together. Signals generated in the retina travel via retinal ganglion cell nerve fibers to the brain. In mice, 85% of retinal ganglion cells connect to the superior colliculus. The superior colliculus provides the majority of early visual processing in these animals. In primates, a highly complex visual cortex takes over more of this visual processing load, but 10% of retinal ganglion cells still connect to the superior colliculus, which manages basic but necessary perceptual tasks.

One of these tasks is detecting that a visual event has occurred. The superior colliculus takes in information from the retina and cortex, and when there is sufficient evidence that an event has taken place in the visual field, neurons in the superior colliculus fire. Classical experiments into perceptual decision-making involve having a subject, like a person or a monkey, look at an image of vertical grating (a series of blurry vertical black and white lines) and decide if or when the grating rotates slightly. In 2018, Krauzlis and Wang adapted these classic experiments for mice, opening up new avenues for research.

“Although we have to be cautious translating data from mice to humans, because of the difference in visual systems, mice have many of the same basic mechanisms for event detection and visual attention as humans. The genetic tools available for mice allow us to study how specific genes and neurons are involved in controlling perception,” said Lupeng Wang, Ph.D., first author of the study.

In this study, Wang and colleagues used a technique called optogenetics to tightly control the activity of the superior colliculus over time. They used genetically modified mice so that they could turn neurons in the superior colliculus on or off using a beam of light. This on-off switch could be timed precisely, enabling the researchers to determine exactly when the neurons of the superior colliculus were required for detecting visual events. The researchers trained their mice to lick a spout when they’d seen a visual event (a rotation in the vertical grating), and to avoid licking the spout otherwise.

Inhibiting the cells of the superior colliculus made the mice less likely to report that they’d seen an event, and when they did, their decision took longer. The inhibition had to occur within a 100 millisecond (one-tenth of a second) interval after the visual event. If the inhibition was outside that 100-millisecond timeframe, the mouse’s decisions were mostly unaffected. The inhibition was side-specific: because the retinal cells cross over and connect to the superior colliculus on the opposite side of the head (the left eye is connected to the right superior colliculus and vice versa), inhibiting the right side of the superior colliculus depressed responses to stimuli on the left side, but not on the right.

“The ability to temporarily block the transmission of neural signals with such precise timing is one of the great advantages of using optogenetics in mice and reveals exactly when the crucial signals pass through the circuit,” said Wang.

Interestingly, the researchers found that the deficits with superior colliculus inhibition were much more pronounced when the mice were forced to ignore things happening elsewhere in their visual field. Essentially, without the activity of the superior colliculus, the mice were unable to ignore distracting visual events. This ability to ignore visual events, called visual attention, is critical for navigating the complex visual environments of the real world.

“The superior colliculus is a good target for probing these functions because it has a neatly organized map of the visual world. And it is connected to less neatly organized regions, like the basal ganglia, which are directly implicated in a wide range of neuropsychiatric disorders in humans,” said Krauzlis. “It’s sort of like holding the hand of a friend as you reach into the unknown.”

Reconstructing the past to predict future arsenic behaviour

The research team selected a highly arsenic polluted site near Hanoi (Vietnam) to develop and test their computer model. In a first step they used the tiny concentrations of tritium that had entered the groundwater system from the atmosphere during the times of nuclear bomb testing, and its decay product helium, a noble gas, to reconstruct how fast and where the groundwater was moving over the last 5 decades. Once the model simulations were able to match the concentrations that were measured, additional complexity was added to the model in order to simulate how arsenic was mobilised and transported in the Holocene aquifer.

The river-groundwater interface acts as reaction hotspot

At the study site, changes in groundwater flow occurred over the past 50 years since the city of Hanoi markedly increased the extraction of groundwater to satisfy its steadily increasing water demand; this showed to be the main trigger for arsenic pollution in the aquifer. The computer modelling allowed the researchers to pinpoint the source of arsenic down to the river muds that are regularly deposited at the more slow-flowing zones of the Red River. The organic matter contained in those muds fuelled a biogeochemical reaction that led to the release of arsenic and its km-long transport into the aquifer underlying the Van Phuc village, a process that continues to this day. Employing their developed computer model in predictive mode the researchers were able to illustrate the interplay of four key factors on the evolution and longevity of arsenic release at surface water/groundwater interfaces, (i) the abundance of reactive organic matter; (ii) the abundance of iron oxides; (iii) the magnitude of groundwater flow; and (iv) river mud deposition rate.

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Journal Reference:

1. Ilka Wallis, Henning Prommer, Michael Berg, Adam J. Siade, Jing Sun, Rolf Kipfer. The river–groundwater interface as a hotspot for arsenic release. Nature Geoscience, 2020; DOI: 10.1038/s41561-020-0557-6

The study authors say it is not possible to determine whether SARS-CoV-2 coronavirus, which causes COVID-19 disease, will behave likewise. But they hope their findings will help investigators better prepare for what’s to come during the COVID-19 pandemic. Their study appears in the Journal of Infectious Diseases.

“Even though the seasonal coronaviruses found in Michigan are related to SARS-CoV-2, we do not know whether that virus will behave like the seasonal coronaviruses,” said Arnold Monto, the Thomas Francis Collegiate Professor of Epidemiology at the U-M School of Public Health. “Only time will tell if SARS-CoV-2 will become a continuing presence in the respiratory infection landscape, continue with limited circulation as with MERS, or like SARS, disappear from humans altogether.”

The researchers note that while coronaviruses have long been recognized as human respiratory pathogens, human coronaviruses have historically been detected in mild respiratory illnesses; when animal coronaviruses spill over to humans, however, they can cause severe disease. Severe acute respiratory syndrome (SARS) in 2002 and Middle East respiratory syndrome (MERS) in 2012 both emerged when a coronavirus jumped from an animal to people. The COVID-19 pandemic is believed to have started in the same way.

Monto and colleagues used data from the Household Influenza Vaccine Evaluation study, an ongoing longitudinal investigation of respiratory illnesses in households with children in the Ann Arbor area. For the last 10 years, between 890 to 1,441 individuals from several hundred households participated in the study. The continuing study is now tracking the occurrence of SARS-CoV-2 and its potential presence in Michigan households.

In 2010, the study began tracking the occurrence of four typically mild human coronaviruses (OC43, 229E, HKU1 and NL63). The researchers looked at frequency, seasonality and household transmission characteristics of the 993 infections caused by those coronaviruses. They found:

• Overall, 9% of adult cases and 20% of cases in children were associated with doctor visits. On average, 30% of influenza cases require a doctor visit.
• When year-round surveillance occurred, most coronavirus cases were detected between December and April/May, and peaked in January/February. Only 2.5% of the cases occurred between June and September.
• The highest infection frequency was in children under age 5.
• Of the 993 infections, 260 were acquired from an infected household contact.
• The serial interval between index and household-acquired cases ranged from 3.2 to 3.6 days; secondary infection risk ranged from 7.2% to 12.6% by type.
• Cases in children under age 5 and adults over age 50 were more likely to be classified as severe.

Monts and colleagues say that the coronaviruses studied are sharply seasonal in Michigan and appear, based on serial interval and secondary infection risk, to have similar transmission potential to that of the influenza A (H3N2) virus in the study population. They say the results are not indicative of how SARS-CoV-2 will behave.

In a separate ongoing study, the researchers are using samples collected before the COVID-19 pandemic to explore community introduction of SARS-CoV-2. Preliminary results show no evidence that SARS-CoV-2 was present in the community before March.

The study was funded by the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health, through grants R01 AI097150 and R56 AI097150.

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