Ultrabright fluorescent particles via physical encapsulation of fluorescent dyes in mesoporous silica: a mini-review.

Harnessing the power of mesoporous silica to encapsulate organic fluorescent dyes has led to the creation of an extraordinary class of nanocomposite photonic materials. These materials stand out for their ability to produce the brightest fluorescent particles known today, surpassing even the luminosity of quantum dots of similar spectrum and size. The synthesis of these materials offers precise control over the shape and size of the particles, ranging from the nano to the multi-micron scale. Just physical encapsulation of the dyes opens new possibilities for mixing different dyes within individual particles, paving the way for nearly limitless multiplexing capabilities. Moreover, this approach lays the groundwork for the development of highly sensitive sensors capable of detecting subtle changes in temperature and acidity at the nanoscale, among other parameters. This mini-review highlights the mechanism of synthesis, explains the nature of ultrabrightness, and describes the recent advancements and future prospects in the field of ultrabright fluorescent mesoporous silica particles, showcasing their potential for various applications.

Toward Real Chemical Accuracy on Current Quantum Hardware Through the Transcorrelated Method.

Quantum computing is emerging as a new computational paradigm with the potential to transform several research fields including quantum chemistry. However, current hardware limitations (including limited coherence times, gate infidelities, and connectivity) hamper the implementation of most quantum algorithms and call for more noise-resilient solutions. We propose an explicitly correlated Ansatz based on the transcorrelated (TC) approach to target these major roadblocks directly. This method transfers, without any approximation, correlations from the wave function directly into the Hamiltonian, thus reducing the resources needed to achieve accurate results with noisy quantum devices. We show that the TC approach allows for shallower circuits and improves the convergence toward the complete basis set limit, providing energies within chemical accuracy to experiment with smaller basis sets and, thus, fewer qubits. We demonstrate our method by computing bond lengths, dissociation energies, and vibrational frequencies close to experimental results for the hydrogen dimer and lithium hydride using two and four qubits, respectively. To demonstrate our approach's current and near-term potential, we perform hardware experiments, where our results confirm that the TC method paves the way toward accurate quantum chemistry calculations already on today's quantum hardware.

Machine Learning Allows for Distinguishing Precancerous and Cancerous Human Epithelial Cervical Cells Using High-Resolution AFM Imaging of Adhesion Maps.

Previously, the analysis of atomic force microscopy (AFM) images allowed us to distinguish normal from cancerous/precancerous human epithelial cervical cells using only the fractal dimension parameter. High-resolution maps of adhesion between the AFM probe and the cell surface were used in that study. However, the separation of cancerous and precancerous cells was rather poor (the area under the curve (AUC) was only 0.79, whereas the accuracy, sensitivity, and specificity were 74%, 58%, and 84%, respectively). At the same time, the separation between premalignant and malignant cells is the most significant from a clinical point of view. Here, we show that the introduction of machine learning methods for the analysis of adhesion maps allows us to distinguish precancerous and cancerous cervical cells with rather good precision (AUC, accuracy, sensitivity, and specificity are 0.93, 83%, 92%, and 78%, respectively). Substantial improvement in sensitivity is significant because of the unmet need in clinical practice to improve the screening of cervical cancer (a relatively low specificity can be compensated by combining this approach with other currently existing screening methods). The random forest decision tree algorithm was utilized in this study. The analysis was carried out using the data of six precancerous primary cell lines and six cancerous primary cell lines, each derived from different humans. The robustness of the classification was verified using K-fold cross-validation (K = 500). The results are statistically significant at p < 0.0001. Statistical significance was determined using the random shuffle method as a control.

Mechanical Way To Study Molecular Structure of Pericellular Layer.

Atomic force microscopy (AFM) has been used to study the mechanical properties of cells, in particular, malignant cells. Softening of various cancer cells compared to their nonmalignant counterparts has been reported for various cell types. However, in most AFM studies, the pericellular layer was ignored. As was shown, it could substantially change the measured cell rigidity and miss important information on the physical properties of the pericellular layer. Here we take into account the pericellular layer by using the brush model to do the AFM indentation study of bladder epithelial bladder nonmalignant (HCV29) and cancerous (TCCSUP) cells. It allows us to measure not only the quasistatic Young's modulus of the cell body but also the physical properties of the pericellular layer (the equilibrium length and grafting density). We found that the inner pericellular brush was longer for cancer cells, but its grafting density was similar to that found for nonmalignant cells. The outer brush was much shorter and less dense for cancer cells. Furthermore, we demonstrate a method to convert the obtained physical properties of the pericellular layer into biochemical language better known to the cell biology community. It is done by using heparinase I and neuraminidase enzymatic treatments that remove specific molecular parts of the pericellular layer. The presented here approach can also be used to decipher the molecular composition of not only pericellular but also other molecular layers.

Synchronization transitions in Kuramoto networks with higher-mode interaction.

Synchronization is an omnipresent collective phenomenon in nature and technology, whose understanding is still elusive for real-world systems in particular. We study the synchronization transition in a phase oscillator system with two nonvanishing Fourier-modes in the interaction function, hence going beyond the Kuramoto paradigm. We show that the transition scenarios crucially depend on the interplay of the two coupling modes. We describe the multistability induced by the presence of a second coupling mode. By extending the collective coordinate approach, we describe the emergence of various states observed in the transition from incoherence to coherence. Remarkably, our analysis suggests that, in essence, the two-mode coupling gives rise to states characterized by two independent but interacting groups of oscillators. We believe that these findings will stimulate future research on dynamical systems, including complex interaction functions beyond the Kuramoto-type.

Towards the Use of Individual Fluorescent Nanoparticles as Ratiometric Sensors: Spectral Robustness of Ultrabright Nanoporous Silica Nanoparticles.

Here we address an important roadblock that prevents the use of bright fluorescent nanoparticles as individual ratiometric sensors: the possible variation of fluorescence spectra between individual nanoparticles. Ratiometric measurements using florescent dyes have shown their utility in measuring the spatial distribution of temperature, acidity, and concentration of various ions. However, the dyes have a serious limitation in their use as sensors; namely, their fluorescent spectra can change due to interactions with the surrounding dye. Encapsulation of the d, e in a porous material can solve this issue. Recently, we demonstrated the use of ultrabright nanoporous silica nanoparticles (UNSNP) to measure temperature and acidity. The particles have at least two kinds of encapsulated dyes. Ultrahigh brightness of the particles allows measuring of the signal of interest at the single particle level. However, it raises the problem of spectral variation between particles, which is impossible to control at the nanoscale. Here, we study spectral variations between the UNSNP which have two different encapsulated dyes: rhodamine R6G and RB. The dyes can be used to measure temperature. We synthesized these particles using three different ratios of the dyes. We measured the spectra of individual nanoparticles and compared them with simulations. We observed a rather small variation of fluorescence spectra between individual UNSNP, and the spectra were in very good agreement with the results of our simulations. Thus, one can conclude that individual UNSNP can be used as effective ratiometric sensors.

Eight new species of the genus Nesamblyops Jeannel (Anillini: Carabidae: Coleoptera) from New Zealand with notes about dispersal of the genus to the North Island.

Species of flightless litter ground beetles of the tribe Anillini, genus Nesamblyops, from the North Island and from the north-eastern part of the South Island are revised. Eight new species are described and one previously known species, Nesamblyops oreobius (Broun), is re-described. Nesamblyops oreobius, the only hitherto recorded species from the North Island, is most similar to the group of two new species from the South Island, N. confusus n. sp. (type locality: New Zealand, Marlborough Sounds, Mount Stokes) and N. lescheni n. sp. (type locality: New Zealand, Marlborough Sounds, D'Urville Island), based on the structure of the male genitalia. The second species of the genus known from the North Island, N. tararua n. sp. (type locality: New Zealand, Wellington, Tararua Range) represents another lineage, based on the structure of the male genitalia, and is closely related to a group of three new species from the South Island, N. brouni n. sp. (type locality: New Zealand, Canterbury, Southern Alps, Lewis Pass), N. distinctus n. sp. (type locality: New Zealand, Marlborough, Richmond Range, Fabians Valley), and N. townsendi n. sp. (type locality: New Zealand, Marlborough Sounds, Tennyson Inlet). Nesamblyops carltoni n. sp. (type locality: New Zealand, Nelson, Richmond Range, Dun Mountain) and N. parvulus n. sp. (type locality: New Zealand, Marlborough Sounds, Mount Stokes), both from the South Island occupy an isolated position among the examined species. All species are illustrated with digital images of habitus, body parts, and drawings of genitalia. Distribution maps for all species are also provided. Geographical evidence of Nesamblyops dispersal to the North Island is discussed, based on distributional data.

Heterogeneous Nucleation in Finite-Size Adaptive Dynamical Networks.

Phase transitions in equilibrium and nonequilibrium systems play a major role in the natural sciences. In dynamical networks, phase transitions organize qualitative changes in the collective behavior of coupled dynamical units. Adaptive dynamical networks feature a connectivity structure that changes over time, coevolving with the nodes' dynamical state. In this Letter, we show the emergence of two distinct first-order nonequilibrium phase transitions in a finite-size adaptive network of heterogeneous phase oscillators. Depending on the nature of defects in the internal frequency distribution, we observe either an abrupt single-step transition to full synchronization or a more gradual multistep transition. This observation has a striking resemblance to heterogeneous nucleation. We develop a mean-field approach to study the interplay between adaptivity and nodal heterogeneity and describe the dynamics of multicluster states and their role in determining the character of the phase transition. Our work provides a theoretical framework for studying the interplay between adaptivity and nodal heterogeneity.

Linear Response and Fluctuation-Dissipation Relations for Brownian Motion under Resetting.

We consider fluctuation-dissipation relations (FDRs) for a Brownian motion under renewal resetting with arbitrary waiting time distribution between the resetting events. We show that if the distribution of waiting times of the resetting process possesses the second moment, the usual (generalized) FDR and the equivalent generalized Einstein's relation (GER) apply for the response function of the coordinate. If the second moment of waiting times diverges but the first one stays finite, the static susceptibility diverges, the usual FDR breaks down, but the GER still applies. In any of these situations, the fluctuation dissipation relations define the effective temperature of the system which is twice as high as the temperature of the medium in which the Brownian motion takes place.

Decoding the double trouble: A mathematical modelling of co-infection dynamics of SARS-CoV-2 and influenza-like illness.

After the detection of coronavirus disease 2019 (Covid-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Wuhan, Hubei Province, China in late December, the cases of Covid-19 have spiralled out around the globe. Due to the clinical similarity of Covid-19 with other flulike syndromes, patients are assayed for other pathogens of influenza like illness. There have been reported cases of co-infection amongst patients with Covid-19. Bacteria for example Streptococcus pneumoniae, Staphylococcus aureus, Klebsiella pneumoniae, Mycoplasma pneumoniae, Chlamydia pneumonia, Legionella pneumophila etc and viruses such as influenza, coronavirus, rhinovirus/enterovirus, parainfluenza, metapneumovirus, influenza B virus etc are identified as co-pathogens. In our current effort, we develop and analysed a compartmental based Ordinary Differential Equation (ODE) type mathematical model to understand the co-infection dynamics of Covid-19 and other influenza type illness. In this work we have incorporated the saturated treatment rate to take account of the impact of limited treatment resources to control the possible Covid-19 cases. As results, we formulate the basic reproduction number of the model system. Finally, we have performed numerical simulations of the co-infection model to examine the solutions in different zones of parameter space.

Identification of Geometrical Features of Cell Surface Responsible for Cancer Aggressiveness: Machine Learning Analysis of Atomic Force Microscopy Images of Human Colorectal Epithelial Cells.

It has been recently demonstrated that atomic force microscopy (AFM) allows for the rather precise identification of malignancy in bladder and cervical cells. Furthermore, an example of human colorectal epithelial cells imaged in AFM Ringing mode has demonstrated the ability to distinguish cells with varying cancer aggressiveness with the help of machine learning (ML). The previously used ML methods analyzed the entire cell image. The problem with such an approach is the lack of information about which features of the cell surface are associated with a high degree of aggressiveness of the cells. Here we suggest a machine-learning approach to overcome this problem. Our approach identifies specific geometrical regions on the cell surface that are critical for classifying cells as highly or lowly aggressive. Such localization gives a path to colocalize the newly identified features with possible clustering of specific molecules identified via standard bio-fluorescence imaging. The biological interpretation of the obtained information is discussed.

Fourteen new species of the genus Nesamblyops Jeannel (Coleoptera: Carabidae: Anillini) from the South Island of New Zealand with redescription of the genus and description of a new subtribe.

Fourteen new species of flightless litter ground beetles of the tribe Anillini, genus Nesamblyops, from the South Island of New Zealand, are described. The only hitherto described species from the South Island, Nesamblyops subcaecus (Broun), is similar to the new species from Southland, N. viator n. sp. (type locality: New Zealand, South Island, Fiordland, Resolution Island), based on the structure of male genitalia. The species assembly inhabiting the northwest corner of the South Island comprises two partly sympatric groups composed of three related allopatric species each. The first group includes N. canaanensis n. sp. (type locality: New Zealand, South Island, Nelson, Abel Tasman National Park, Canaan area), N. hobbit n. sp. (type locality: New Zealand, South Island, Nelson, Kahurangi National Park, Mt Domett), and N. ovipennis n. sp. (type locality: New Zealand, South Island, Nelson, Kahurangi National Park, Mt Arthur). The second group represents another lineage and contains N. rotundicollis n. sp. (type locality: New Zealand, South Island, Nelson, Kahurangi National Park, Onekaka area), N. solitarius n. sp. (type locality: New Zealand, South Island, West Coast, western foothills of Victoria Range, Capleston area), and N. subrufus n. sp. (type locality: New Zealand, South Island, West Coast, Upper Buller Gorge, Dublin Terrace). Three additional species known from the northwest corner of the South Island, based on the structure of male genitalia, are unrelated to each other and remaining species of the region. These are N. karamea n. sp. (type locality: New Zealand, South Island, West Coast, Kahurangi National Park, the Karamea River Gorge area), N. montanus n. sp. (type locality: New Zealand, South Island, Nelson, Kahurangi National Park, Lake Sylvester area), and N. kuscheli n. sp. (type locality: New Zealand, South Island, Nelson, Kahurangi National Park, Mt Arthur). The latter species is presumably closely related to the species from the central parts of the West Coast, N. moorei n. sp., (type locality: New Zealand, South Island, West Coast, Ngahere area, Mawhera Forest). Additionally, the central part of the West Coast is inhabited by a small group of two species, N. disjunctus n. sp. (type locality: New Zealand, South Island, West Coast, E slope of the Paparoa Range, Fletcher Creek area), and N. victoriae n. sp. (type locality: New Zealand, South Island, West Coast, Victoria Range, Capleston area). According to the structure of the male genitalia, this group represents a separate lineage within the genus. The most unusual structure of male genitalia belongs to a species without eyes, a trait previously unknown in Nesamblyops, N. magnificus n. sp. (type locality: New Zealand, South Island, Coastal Otago, Allison Conservation Area) that inhabits the southeast corner of the South Island. Digital images of habitus, body parts, drawings of genitalia, as well as distribution maps are provided for all described species. Morphological evidence of the isolated position of Nesamblyops within the tribe Anillini is discussed, with a focus on the morphological comparison of Nesamblyops with the members of Anillini, Tachyini, Bembidiini, Zolini, and Sinozolini, and on the data of published molecular analyses. A new subtribe for the representatives of the genus, Nesamblyopina, n. subtr., is proposed; the newly discovered morphological characters have been incorporated in the redescription of the genus.

Finite-time recurrence analysis of chaotic trajectories in Hamiltonian systems.

In this work, we show that a finite-time recurrence analysis of different chaotic trajectories in two-dimensional non-linear Hamiltonian systems provides useful prior knowledge of their dynamical behavior. By defining an ensemble of initial conditions, evolving them until a given maximum iteration time, and computing the recurrence rate of each orbit, it is possible to find particular trajectories that widely differ from the average behavior. We show that orbits with high recurrence rates are the ones that experience stickiness, being dynamically trapped in specific regions of the phase space. We analyze three different non-linear maps and present our numerical observations considering particular features in each of them. We propose the described approach as a method to visually illustrate and characterize regions in phase space with distinct dynamical behaviors.

Ticks on the Run: A Mathematical Model of Crimean-Congo Haemorrhagic Fever (CCHF)-Key Factors for Transmission.

Crimean-Congo haemorrhagic fever (CCHF) is a zoonotic disease caused by the Crimean-Congo hemorrhagic fever virus (CCHFV). Ticks of the genus Hyalomma are the main vectors and represent a reservoir for the virus. CCHF is maintained in nature in an endemic vertebrate-tick-vertebrate cycle. The disease is prevalent in wide geographical areas including Asia, Africa, South-Eastern Europe and the Middle East. It is of great importance for the public health given its occasionally high case/fatality ratio of CCHFV in humans. Climate change and the detection of possible CCHFV vectors in Central Europe suggest that the establishment of the transmission in Central Europe may be possible in future. We have developed a compartment-based nonlinear Ordinary Differential Equation (ODE) system to model the disease transmission cycle including blood sucking ticks, livestock and human. Sensitivity analysis of the basic reproduction number R0 shows that decreasing the tick survival time is an efficient method to control the disease. The model supports us in understanding the influence of different model parameters on the spread of CCHFV. Tick-to-tick transmission through co-feeding and the CCHFV circulation through transstadial and transovarial transmission are important factors to sustain the disease cycle. The proposed model dynamics are calibrated through an empirical multi-country analysis and multidimensional plot reveals that the disease-parameter sets of different countries burdened with CCHF are different. This information may help decision makers to select efficient control strategies.

Influence of the Carbidized Tungsten Surface on the Processes of Interaction with Helium Plasma.

This paper presents the results of experimental studies of the interaction of helium plasma with a near-surface tungsten carbide layer. The experiments were implemented at the plasma-beam installation. The helium plasma loading conditions were close to those expected in the ITER divertor. The technology of the plasma irradiation was applied in a stationary type linear accelerator. The impact of the helium plasma was realized in the course of the experiment with the temperatures of ~905 °C and ~1750 °C, which were calculated by simulating heat loading on a tungsten monoblock of the ITER divertor under the plasma irradiation at the load of 10 MW/m2 and 20 MW/m2, respectively. The structure was investigated with scanning microscopy, transmitting electron microscopy and X-ray analysis. The data were obtained showing that the surface morphology changed due to the erosion. It was found that the carbidization extremely impacted the plasma-tungsten interaction, as the plasma-tungsten interaction with the carbide layer led to the carbon sputtering and partial diffusion towards to the depth of the sample. According to these results, WC-based tungsten carbide is less protected against fracture by helium than W and W2C. An increase in temperature leads to much more extensive surface damage accompanied by the formation of molten and recrystallized flanges.

Loss of NECTIN1 triggers melanoma dissemination upon local IGF1 depletion.

Cancer genetics has uncovered many tumor-suppressor and oncogenic pathways, but few alterations have revealed mechanisms involved in tumor spreading. Here, we examined the role of the third most significant chromosomal deletion in human melanoma that inactivates the adherens junction gene NECTIN1 in 55% of cases. We found that NECTIN1 loss stimulates melanoma cell migration in vitro and spreading in vivo in both zebrafish and human tumors specifically in response to decreased IGF1 signaling. In human melanoma biopsy specimens, adherens junctions were seen exclusively in areas with low IGF1 levels, but not in NECTIN1-deficient tumors. Our study establishes NECTIN1 as a major determinant of melanoma dissemination and uncovers a genetic control of the response to microenvironmental signals.

Time-averaging and nonergodicity of reset geometric Brownian motion with drift.

How do near-bankruptcy events in the past affect the dynamics of stock-market prices in the future? Specifically, what are the long-time properties of a time-local exponential growth of stock-market prices under the influence of stochastically occurring economic crashes? Here, we derive the ensemble- and time-averaged properties of the respective "economic" or geometric Brownian motion (GBM) with a nonzero drift exposed to a Poissonian constant-rate price-restarting process of "resetting." We examine-based both on thorough analytical calculations and on findings from systematic stochastic computer simulations-the general situation of reset GBM with a nonzero [positive] drift and for all special cases emerging for varying parameters of drift, volatility, and reset rate in the model. We derive and summarize all short- and long-time dependencies for the mean-squared displacement (MSD), the variance, and the mean time-averaged MSD (TAMSD) of the process of Poisson-reset GBM under the conditions of both rare and frequent resetting. We consider three main regions of model parameters and categorize the crossovers between different functional behaviors of the statistical quantifiers of this process. The analytical relations are fully supported by the results of computer simulations. In particular, we obtain that Poisson-reset GBM is a nonergodic stochastic process, with generally MSD(Δ)≠TAMSD(Δ) and Variance(Δ)≠TAMSD(Δ) at short lag times Δ and for long trajectory lengths T. We investigate the behavior of the ergodicity-breaking parameter in each of the three regions of parameters and examine its dependence on the rate of reset at Δ/T≪1. Applications of these theoretical results to the analysis of prices of reset-containing options are pertinent.

Acceleration of imaging in atomic force microscopy working in sub-resonance tapping mode.

Sub-resonance tapping (SRT) mode of atomic force microscopy (AFM) enables researchers to image surfaces with well-controlled load forces and to collect maps of multiple physical properties of samples. The major bottleneck of this mode is a relatively low scan speed compared to other scanning modes. This paper presents a novel control algorithm that substantially improves the scanning speed over the standard SRT. We propose naming the new modality Trajectory Tracking SRT (TT-SRT). In contrast with the standard SRT control, TT-SRT uses the feedback within every single touch of the sample by the AFM probe. To demonstrate the advantage of TT-SRT, we conduct scans on a variety of samples with differing topologies, roughnesses, and mechanical properties. Each sample region is scanned with both standard SRT and TT-SRT at the same set of speeds. The control gains are tuned before each scan for maximum performance in each mode. Performance is evaluated by selecting a given level of image quality and finding the maximum speed that can be achieved by each algorithm. We find that with increased demand for data quality, the utility of TT-SRT becomes more apparent; for example, the speed of TT-SRT can be ten times faster or more than standard SRT for a reasonable expectation of data quality.

At Least 10-fold Higher Lubricity of Molecularly Thin D2O vs H2O Films at Single-Layer Graphene-Mica Interfaces.

Interfacial water is a widespread lubricant down to the nanometer scale. We investigate the lubricities of molecularly thin H2O and D2O films confined between mica and graphene, via the relaxation of initially applied strain in graphene employing Raman spectroscopy. Surprisingly, the D2O films are at least 1 order of magnitude more lubricant than H2O films, despite the similar bulk viscosities of the two liquids. We propose a mechanism based on the known selective permeation of protons vs deuterons through graphene. Permeated protons and left behind hydroxides may form ion pairs clamping across the graphene sheet and thereby hindering the graphene from sliding on the water layer. This explains the lower lubricity but also the hindering diffusivity of the water layer, which yields a high effective viscosity in accordance with findings in dewetting experiments. Our work elucidates an unexpected effect and provides clues to the behavior of graphene on hydrous surfaces.

Correlation of cell mechanics with the resistance to malignant transformation in naked mole rat fibroblasts.

Naked mole rats (NMRs) demonstrate exceptional longevity and resistance to cancer. Using a biochemical approach, it was previously shown that the treatment of mouse fibroblast cells with RasV12 oncogene and SV40 Large T antigen (viral oncoprotein) led to malignant transformations of cells. In contrast, NMR fibroblasts were resistant to malignant transformations upon this treatment. Here we demonstrate that atomic force microscopy (AFM) can provide information which is in agreement with the above finding, and further, adds unique information about the physical properties of cells that is impossible to obtain by other existing techniques. AFM indentation data were collected from individual cells and subsequently processed through the brush model to obtain information about the mechanics of the cell body (absolute values of the effective Young's moduli). Furthermore, information about the physical properties of the pericellular layer surrounding the cells was obtained. We found a statistically significant decrease in the rigidity of mouse cells after the treatment, whereas there was no significant change found in the rigidity of NMR cells upon the treatment. We also found that the treatment caused a substantial increase in a long part of the pericellular layer in NMR cells only (the long brush was defined as having a size of >10 microns). The mouse cells and smaller brush did not show statistically significant changes upon treatment. The observed change in cell mechanics is in agreement with the frequently observed decrease in cell rigidity during progression towards cancer. The change in the pericellular layer due to the malignant transformation of fibroblast cells has practically not been studied, though it was shown that the removal of part of the pericellular layer of NMR fibroblasts made the cells susceptible to malignant transformation. Although it is plausible to speculate that the observed increase in the long part of the brush layer of NMR cells might help cells to resist malignant transformations, the significance of the observed change in the pericellular layer is yet to be understood. As of now, we can conclude that changes in cell mechanics might be used as an indication of the resistance of NMR cells to malignant transformations.