A massive rock and ice avalanche caused the 2021 disaster at Chamoli, Indian Himalaya.

On 7 February 2021, a catastrophic mass flow descended the Ronti Gad, Rishiganga, and Dhauliganga valleys in Chamoli, Uttarakhand, India, causing widespread devastation and severely damaging two hydropower projects. More than 200 people were killed or are missing. Our analysis of satellite imagery, seismic records, numerical model results, and eyewitness videos reveals that ~27 × 106 cubic meters of rock and glacier ice collapsed from the steep north face of Ronti Peak. The rock and ice avalanche rapidly transformed into an extraordinarily large and mobile debris flow that transported boulders greater than 20 meters in diameter and scoured the valley walls up to 220 meters above the valley floor. The intersection of the hazard cascade with downvalley infrastructure resulted in a disaster, which highlights key questions about adequate monitoring and sustainable development in the Himalaya as well as other remote, high-mountain environments.

Ultrabright fluorescent nanothermometers.

Here we report on the first ultrabright fluorescent nanothermometers, ∼50 nm-size particles, capable of measuring temperature in 3D and down to the nanoscale. The temperature is measured through the recording of the ratio of fluorescence intensities of fluorescent dyes encapsulated inside the nanochannels of the silica matrix of each nanothermometer. The brightness of each particle excited at 488 nm is equivalent to the fluorescence coming from 150 molecules of rhodamine 6G and 1700 molecules of rhodamine B dyes. The fluorescence of both dyes is excited with a single wavelength due to the Förster resonance energy transfer (FRET). We demonstrate repeatable measurements of temperature with the uncertainty down to 0.4 K and a constant sensitivity of ∼1%/K in the range of 20-50 °C, which is of particular interest for biomedical applications. Due to the high fluorescence brightness, we demonstrate the possibility of measurement of accurate 3D temperature distributions in a hydrogel. The accuracy of the measurements is confirmed by numerical simulations. We further demonstrate the use of single nanothermometers to measure temperature. As an example, 5-8 nanothermometers are sufficient to measure temperature with an error of 2 K (with the measurement time of >0.7 s).

Difference in biophysical properties of cancer-initiating cells in melanoma mutated zebrafish.

Despite sharing oncogenetic mutations, only a small number of cells within a given tissue will undergo malignant transformation. Biochemical and physical factors responsible for this cancer-initiation process are not well understood. Here we study biophysical differences of pre-melanoma and melanoma cells in a BRAFV600E/P53 zebrafish model. The AFM indentation technique was used to study the cancer-initiating cells while the surrounding melanocytes were the control. We observed a statistically significant decrease in the modulus of elasticity (the effective Young's modulus) of cancer-initiating cells compared to the surrounding melanocytes. No significant differences in the pericellular coat surrounding cells were observed. These results contribute to a better understanding of the factors responsible for the initiation of cancer.

Noninvasive diagnostic imaging using machine-learning analysis of nanoresolution images of cell surfaces: Detection of bladder cancer.

We report an approach in diagnostic imaging based on nanoscale-resolution scanning of surfaces of cells collected from body fluids using a recent modality of atomic force microscopy (AFM), subresonance tapping, and machine-leaning analysis. The surface parameters, which are typically used in engineering to describe surfaces, are used to classify cells. The method is applied to the detection of bladder cancer, which is one of the most common human malignancies and the most expensive cancer to treat. The frequent visual examinations of bladder (cytoscopy) required for follow-up are not only uncomfortable for the patient but a serious cost for the health care system. Our method addresses an unmet need in noninvasive and accurate detection of bladder cancer, which may eliminate unnecessary and expensive cystoscopies. The method, which evaluates cells collected from urine, shows 94% diagnostic accuracy when examining five cells per patient's urine sample. It is a statistically significant improvement (P < 0.05) in diagnostic accuracy compared with the currently used clinical standard, cystoscopy, as verified on 43 control and 25 bladder cancer patients.

Nanoscale compositional mapping of cells, tissues, and polymers with ringing mode of atomic force microscopy.

Recently developed sub-resonance tapping modes (such as Digital Pulse, Peak Force Tapping, HybriD, etc.) of atomic force microscopy (AFM) allow imaging of compositional contrast of (bio)materials and biological cells down to the nanoscale. Here we report on a powerful extension of those modes, "ringing" mode, which more than doubles the number of non-trivial physical channels that can be collected with a regular sub-resonance tapping. It can simultaneously record five new additional compositional parameters related to adhesive and viscoelastic properties of the sample surface: the restored (averaged) adhesion, adhesion height, pull-off neck height, detachment distance, and detachment energy losses. Ringing mode can be up to 20 times faster and showing fewer artifacts compared to the existing sub-resonance tapping modes. Ringing mode is based on an analysis of ringing signal of the AFM cantilever after detaching the AFM probe from the sample surface (this signal is currently treated as noise, and typically filtered out in the existing modes). We demonstrate that this new mode allows recording robust and unique information on fixed human epithelial cells, corneocyte skin flakes, and polymers used for bioimplants.

High-resolution high-speed dynamic mechanical spectroscopy of cells and other soft materials with the help of atomic force microscopy.

Dynamic mechanical spectroscopy (DMS), which allows measuring frequency-dependent viscoelastic properties, is important to study soft materials, tissues, biomaterials, polymers. However, the existing DMS techniques (nanoindentation) have limited resolution when used on soft materials, preventing them from being used to study mechanics at the nanoscale. The nanoindenters are not capable of measuring cells, nanointerfaces of composite materials. Here we present a highly accurate DMS modality, which is a combination of three different methods: quantitative nanoindentation (nanoDMA), gentle force and fast response of atomic force microscopy (AFM), and Fourier transform (FT) spectroscopy. This new spectroscopy (which we suggest to call FT-nanoDMA) is fast and sensitive enough to allow DMS imaging of nanointerfaces, single cells, while attaining about 100x improvements on polymers in both spatial (to 10-70 nm) and temporal resolution (to 0.7 s/pixel) compared to the current art. Multiple frequencies are measured simultaneously. The use of 10 frequencies are demonstrated here (up to 300 Hz which is a rather relevant range for biological materials and polymers, in both ambient conditions and liquid). The method is quantitatively verified on known polymers and demonstrated on cells and polymers blends. Analysis shows that FT-nanoDMA is highly quantitative. The FT-nanoDMA spectroscopy can easily be implemented in the existing AFMs.

Emerging of fractal geometry on surface of human cervical epithelial cells during progression towards cancer.

Despite considerable advances in understanding the molecular nature of cancer, many biophysical aspects of malignant development are still unclear. Here we study physical alterations of the surface of human cervical epithelial cells during stepwise in vitro development of cancer (from normal to immortal (premalignant), to malignant). We use atomic force microscopy to demonstrate that development of cancer is associated with emergence of simple fractal geometry on the cell surface. Contrary to the previously expected correlation between cancer and fractals, we find that fractal geometry occurs only at a limited period of development when immortal cells become cancerous; further cancer progression demonstrates deviation from fractal. Because of the connection between fractal behaviour and chaos (or far from equilibrium behaviour), these results suggest that chaotic behaviour coincides with the cancer transformation of the immortalization stage of cancer development, whereas further cancer progression recovers determinism of processes responsible for cell surface formation.

On averaging force curves over heterogeneous surfaces in atomic force microscopy.

Atomic force microscopy (AFM) can be used to study mechanics at the nanoscale. Biological surfaces and nanocomposites have typically heterogeneous surfaces, both mechanically and chemically. When studying such surfaces with AFM, one needs to collect a large amount of data to make statistically sound conclusions. It is time- and resource-consuming to process each force curve separately. The analysis of an averaged raw force data is a simple and time saving option, which also averages out the noise and measurement artifacts of the force curves being analyzed. Moreover, some biomedical applications require just an average number per biological cell. Here we investigate such averaging, study the possible artifacts due to the averaging, and demonstrate how to minimize or even to avoid them. We analyze two ways of doing the averaging: over the force data for each particular distance (method 1, the most commonly used way), and over the distances for each particular force (method 2). We derive the errors of the methods in finding to the true average rigidity modulus. We show that both methods are accurate (the error is <2%) when the heterogeneity of the surface rigidity is small (<50%). When the heterogeneity is large (>100×), method 2 underestimates the average rigidity modulus by a factor of 2, whereas the error of method 1 is only 15%. However, when analyzing the different surface chemistry, which reveals itself in the changing long-range forces, the accuracy of the methods behave oppositely: method 1 can produce a noticeable averaging artifact in the deriving of the long-range forces; whereas method 2 can be successfully used to derive the averaged long-range force parameters without artifacts. We exemplify our conclusions by the study of human cervical cancer and normal epithelial cells, which demonstrate different degrees of heterogeneity.

Cell surface as a fractal: normal and cancerous cervical cells demonstrate different fractal behavior of surface adhesion maps at the nanoscale.

Here we show that the surface of human cervical epithelial cells demonstrates substantially different fractal behavior when the cell becomes cancerous. Analyzing the adhesion maps of individual cervical cells, which were obtained using the atomic force microscopy operating in the HarmoniX mode, we found that cancerous cells demonstrate simple fractal behavior, whereas normal cells can only be approximated at best as multifractal. Tested on ~300 cells collected from 12 humans, the fractal dimensionality of cancerous cells is found to be unambiguously higher than that for normal cells.

Towards nano-physiology of insects with atomic force microscopy.

Little study of insects with modern nanotechnology tools has been done so far. Here we use one of such tool, atomic force microscopy (AFM) to study surface oscillations of the ladybird beetles (Hippodamia convergens) measured in different parts of the insect at picometer level. This allows us to record a much broader spectral range of possible surface vibrations (up to several kHz) than the previously studied oscillations due to breathing, heartbeat cycles, coelopulses, etc. (up to 5-10Hz). Here we demonstrate three different ways with which one can identify the origins of the observed peaks - by physical positioning the probe near a specific organ, and by using biological or chemical stimuli. We report on identification of high frequency peaks associated with H. convergens heart, spiracular closer muscles, and oscillations associated with muscles activated while drinking. The method, being a relatively non-invasive technique providing a new type of information, may be useful in developing "nanophysiology" of insects.

A novel in vitro stripping method to study geometry of corneocytes with fluorescent microscopy: example of aging skin.

BACKGROUND/PURPOSE: To develop modification of stripping method allowing high-resolution fluorescent visualization of corneocytes of human skin in vitro. To validate the method, the measured corneocyte areas on skin flakes are collected from individuals of different ages. MATERIALS AND METHODS: Two complimentary fluorescent dyes were used sequentially. First the adhesive layer of the stripping tape was stained with a cationic dye (rhodamine 640). This tape was used to collect skin flakes. Then both the tape and collected flakes were stained with anionic dye (fluorescein). The fluorescence of the adhesive tape exposed to the second staining is substantially decreased due to the mutual quenching of the dyes. Thirteen healthy, 6-86-year-old males participated to validate the method. The measurements were done on backhand and forearm. RESULTS: The method allows high-resolution imaging of corneocytes by means of fluorescent microscopy. Both absolute areas and the dependence of corneocyte areas on the individual age are in good agreement with the data reported previously. CONCLUSION: The developed method is fast and easy. It requires minimum interaction with the individual and allows using a broad variety of fluorescent dyes that may be potentially unsafe but beneficial for imaging. It can be used on any part of human or animal body.

Reverse and enhanced magneto-optics of opal-garnet heterostructures.

Magnetophotonic heterostructures comprising two thin opal films and a layer of bismuth-substituted yttrium iron garnet were fabricated. Such heterostructures combined properties of 1D, 2D and 3D photonic crystals. Their spectra demonstrated various optical resonances resulting in reverse and enhanced magneto-optical responses.