Global and single-nucleotide resolution detection of 7-methylguanosine in RNA.

RNA modifications, including N-7-methylguanosine (m7G), are pivotal in governing RNA stability and gene expression regulation. The accurate detection of internal m7G modifications is of paramount significance, given recent associations between altered m7G deposition and elevated expression of the methyltransferase METTL1 in various human cancers. The development of robust m7G detection techniques has posed a significant challenge in the field of epitranscriptomics. In this study, we introduce two methodologies for the global and accurate identification of m7G modifications in human RNA. We introduce borohydride reduction sequencing (Bo-Seq), which provides base resolution mapping of m7G modifications. Bo-Seq achieves exceptional performance through the optimization of RNA depurination and scission, involving the strategic use of high concentrations of NaBH4, neutral pH and the addition of 7-methylguanosine monophosphate (m7GMP) during the reducing reaction. Notably, compared to NaBH4-based methods, Bo-Seq enhances the m7G detection performance, and simplifies the detection process, eliminating the necessity for intricate chemical steps and reducing the protocol duration. In addition, we present an antibody-based approach, which enables the assessment of m7G relative levels across RNA molecules and biological samples, however it should be used with caution due to limitations associated with variations in antibody quality between batches. In summary, our novel approaches address the pressing need for reliable and accessible methods to detect RNA m7G methylation in human cells. These advancements hold the potential to catalyse future investigations in the critical field of epitranscriptomics, shedding light on the complex regulatory roles of m7G in gene expression and its implications in cancer biology.

Systems Modeling of the Water-Energy-Food-Ecosystems Nexus: Insights from a Region Facing Structural Water Scarcity in Southern Spain.

The complex relationship between water, energy, food, and ecological systems, known as the WEFE nexus, has emerged as a major topic in the debate about sustainable economic development and resource management. This subject is of special interest in Mediterranean coastal areas as rapid economic expansion driven by population growth, higher influx of tourists, and intensification of agriculture is leading to structural water scarcity conditions. However, addressing the diverse range of issues associated with the nexus is a difficult task due to the existence of intricate interconnections, interdependencies, and nonlinearities within and across its various components. Accordingly, this case study applies a combination of participatory systems modeling and network analysis tools to yield insights into the complexity of this nexus in Axarquia, a region with features that make it an example of water-stressed jurisdictions in the Mediterranean. Overall, our results provide a strong foundation to understand the dynamics that govern this nexus in regions where the availability of freshwater resources is a significant concern. Furthermore, they lay the groundwork for the development of models and scenarios to simulate the impact of various policies and interventions on the overall system.

Characterization, Selection, and Microassembly of Nanowire Laser Systems.

Semiconductor nanowire (NW) lasers are a promising technology for the realization of coherent optical sources with ultrasmall footprint. To fully realize their potential in on-chip photonic systems, scalable methods are required for dealing with large populations of inhomogeneous devices that are typically randomly distributed on host substrates. In this work two complementary, high-throughput techniques are combined: the characterization of nanowire laser populations using automated optical microscopy, and a high-accuracy transfer-printing process with automatic device spatial registration and transfer. Here, a population of NW lasers is characterized, binned by threshold energy density, and subsequently printed in arrays onto a secondary substrate. Statistical analysis of the transferred and control devices shows that the transfer process does not incur measurable laser damage, and the threshold binning can be maintained. Analysis on the threshold and mode spectra of the device populations proves the potential for using NW lasers for integrated systems fabrication.

Image edge detection with a photonic spiking VCSEL-neuron.

We report both experimentally and in theory on the detection of edge features in digital images with an artificial optical spiking neuron based on a vertical-cavity surface-emitting laser (VCSEL). The latter delivers fast (< 100 ps) neuron-like optical spikes in response to optical inputs pre-processed using convolution techniques; hence representing image feature information with a spiking data output directly in the optical domain. The proposed technique is able to detect target edges of different directionalities in digital images by applying individual kernel operators and can achieve complete image edge detection using gradient magnitude. Importantly, the neuromorphic (brain-like) spiking edge detection of this work uses commercially sourced VCSELs exhibiting responses at sub-nanosecond rates (many orders of magnitude faster than biological neurons) and operating at the important telecom wavelength of 1300 nm; hence making our approach compatible with optical communication and data-centre technologies.

Vertically Emitting Indium Phosphide Nanowire Lasers.

Semiconductor nanowire (NW) lasers have attracted considerable research effort given their excellent promise for nanoscale photonic sources. However, NW lasers currently exhibit poor directionality and high threshold gain, issues critically limiting their prospects for on-chip light sources with extremely reduced footprint and efficient power consumption. Here, we propose a new design and experimentally demonstrate a vertically emitting indium phosphide (InP) NW laser structure showing high emission directionality and reduced energy requirements for operation. The structure of the laser combines an InP NW integrated in a cat's eye (CE) antenna. Thanks to the antenna guidance with broken asymmetry, strong focusing ability, and high Q-factor, the designed InP CE-NW lasers exhibit a higher degree of polarization, narrower emission angle, enhanced internal quantum efficiency, and reduced lasing threshold. Hence, this NW laser-antenna system provides a very promising approach toward the achievement of high-performance nanoscale lasers, with excellent prospects for use as highly localized light sources in present and future integrated nanophotonics systems for applications in advanced sensing, high-resolution imaging, and quantum communications.

Aerobic and anaerobic microorganisms and antibiotic sensitivity of odontogenic maxillofacial infections.

This study aimed to identify the aerobic and anaerobic causal microorganisms of odontogenic infections and their antibiotic sensitivity. Purulent exudates were taken from patients with odontogenic infections by transdermal puncture, and aerobic and anaerobic microorganisms were identified using biochemical tests. Susceptibility to antibiotics was tested using the Kirby-Bauer method; the inhibition halos were measured according to NCCLS, and based on the results, the microorganisms were classified as susceptible, intermediate or resistant to each antibiotic. Frequencies of species and percentages of resistance were calculated. The microorganisms associated with odontogenic infections were principally anaerobic (65.3% anaerobic vs. 35.7% aerobic), and the susceptibility to antibiotics was higher in anaerobic than in aerobic microorganisms. The majority of isolated microorganisms (82%) showed susceptibility to amoxicillin/clavulanic acid. The causal agents of odontogenic infections were anaerobic microorganisms, which exhibited high resistance to antibiotics.

Integration of Semiconductor Nanowire Lasers with Polymeric Waveguide Devices on a Mechanically Flexible Substrate.

Nanowire lasers are integrated with planar waveguide devices using a high positional accuracy microtransfer printing technique. Direct nanowire to waveguide coupling is demonstrated, with coupling losses as low as -17 dB, dominated by mode mismatch between the structures. Coupling is achieved using both end-fire coupling into a waveguide facet, and from nanowire lasers printed directly onto the top surface of the waveguide. In-waveguide peak powers up to 11.8 µW are demonstrated. Basic photonic integrated circuit functions such as power splitting and wavelength multiplexing are presented. Finally, devices are fabricated on a mechanically flexible substrate to demonstrate robust coupling between the on-chip laser source and waveguides under significant deformation of the system.

Controlled inhibition of spiking dynamics in VCSELs for neuromorphic photonics: theory and experiments.

We report experimentally and theoretically on the controllable inhibition of spiking regimes in a 1300 nm wavelength vertical-cavity surface-emitting laser. Reproducible suppression of spiking dynamics is demonstrated at fast operation speeds (up to sub-ns rates) and with total control on the temporal duration of the spiking inhibition windows. This Letter opens new paths toward a photonic inhibitory neuronal model system for use in future neuromorphic photonic information processing modules and which are able to operate at speeds up to 8 orders of magnitude faster than biological neurons.

Eu9Cd4-xCM2+x-y□ySb9: Ca9Mn4Bi9-type structure stuffed with coinage metals (Cu, Ag, and Au) and the challenges with classical valence theory in describing these possible zintl phases.

The synthesis, crystal structure, magnetic properties, and europium Mössbauer spectroscopy of the new members of the 9-4-9 Zintl family of Eu(9)Cd(4-x)CM(2+x-y)□(y)Sb(9) (CM = coinage metal: Au, Ag, and Cu) are reported. These compounds crystallize in the Ca(9)Mn(4)Bi(9) structure type (9-4-9) with the 4g interstitial site almost half-occupied by coinage metals; these are the first members in the 9-4-9 family where the interstitial positions are occupied by a monovalent metal. All previously known compounds with this structure type include divalent interstitials where these interstitials are typically the same as the transition metals in the anionic framework. Single-crystal magnetic susceptibility data indicate paramagnetic behavior for all three compounds with antiferromagnetic ordering below 10 K (at 100 Oe) that shifts to lower temperature (<7 K) by applying a 3 T magnetic field. (151)Eu Mössbauer spectra were collected on polycrystalline powder samples of Eu(9)Cd(4-x)CM(2+x-y)□(y)Sb(9) at 50 and 6.5 K in order to evaluate the valence of Eu cations. Although the Zintl formalism states that the five crystallographically distinct Eu sites in Eu(9)Cd(4-x)CM(2+x-y)□(y)Sb9 should bear Eu(2+), the Mössbauer spectral isomer shifts are clearly indicative of both 2+ and 3+ valence of the Eu cations with the Cu- and Au-containing compounds showing higher amounts of Eu(3+). This electronic configuration leads to an excess of negative charge in these compounds that contradicts the expected valence-precise requirement of Zintl phases. The spectra obtained at 6.5 K reveal magnetic ordering for both Eu(2+) and Eu(3+). The field dependence of Eu(2+) indicates two distinct magnetic sublattices, with higher and lower fields, and of a small field for Eu(3+). The site symmetry of the five Eu sites is not distinguishable from the Mössbauer data.

Polarization control in GaN nanowire lasers.

We demonstrate polarization control in optically-pumped single GaN nanowire lasers fabricated by a top-down method. By placing the GaN nanowires onto gold substrates, the naturally occurring randomly orientated elliptical polarization of nanowire lasers is converted to a linear polarization that is oriented parallel to the substrate surface. Confirmed by simulation results, this polarization control is attributed to a polarization-dependent loss induced by the gold substrate, which breaks the mode degeneracy of the nanowire and forms two orthogonally polarized modes with largely different cavity losses.

The paradox of success: Water resources closure in Axarquia (southern Spain).

Axarquia is a semi-arid region in southern Spain that in the past 25 years has experienced significant population growth, along with an economic boom driven by an increasing influx of tourists to Costa del Sol and the expansion of irrigated export-oriented subtropical crops. The combination of these factors has led to a chronic structural scarcity condition that has been intensified by the occurrence of a long and extreme drought. As a result, its only reservoir has reached historically low levels and the piezometric levels in its main aquifer have decreased significantly, suggesting that groundwater reserves are being overexploited. The water crisis is impacting citizens (urban supply), farmers (losses of yields and crops), and the environment (decreasing water reserves). The authorities have responded through supply-side measures such as incorporating reclaimed wastewater in the system and planning the deployment of desalination infrastructure in the region, but demand control and proper governance are required to guarantee sustainability. Consequently, in this case study we apply the European Environment Agency's DPSIR (driving forces, pressures, state, impact, and response model of intervention) framework to understand the basin closure process in Axarquia and assess the main actions that have been undertaken by public and private sector stakeholders to address the challenges faced by the region. Our results provide a valuable reference case to support the analysis of similar closure events, the early identification of potential crisis conditions, and the design of potential solutions in water scarce regions in the European Union, the Mediterranean, and elsewhere.

Tunable microwave signal generator with an optically-injected 1310 nm QD-DFB laser.

Tunable microwave signal generation with frequencies ranging from below 1 GHz to values over 40 GHz is demonstrated experimentally with a 1310 nm Quantum Dot (QD) Distributed-Feedback (DFB) laser. Microwave signal generation is achieved using the period 1 dynamics induced in the QD DFB under optical injection. Continuous tuning in the positive detuning frequency range of the quantum dot's unique stability map is demonstrated. The simplicity of the experimental configuration offers promise for novel uses of these nanostructure lasers in Radio-over-Fiber (RoF) applications and future mobile networks.

Artificial optoelectronic spiking neuron based on a resonant tunnelling diode coupled to a vertical cavity surface emitting laser.

Excitable optoelectronic devices represent one of the key building blocks for implementation of artificial spiking neurons in neuromorphic (brain-inspired) photonic systems. This work introduces and experimentally investigates an opto-electro-optical (O/E/O) artificial neuron built with a resonant tunnelling diode (RTD) coupled to a photodetector as a receiver and a vertical cavity surface emitting laser as a transmitter. We demonstrate a well-defined excitability threshold, above which the neuron produces optical spiking responses with characteristic neural-like refractory period. We utilise its fan-in capability to perform in-device coincidence detection (logical AND) and exclusive logical OR (XOR) tasks. These results provide first experimental validation of deterministic triggering and tasks in an RTD-based spiking optoelectronic neuron with both input and output optical (I/O) terminals. Furthermore, we also investigate in simulation the prospects of the proposed system for nanophotonic implementation in a monolithic design combining a nanoscale RTD element and a nanolaser; therefore demonstrating the potential of integrated RTD-based excitable nodes for low footprint, high-speed optoelectronic spiking neurons in future neuromorphic photonic hardware.

Optically-pumped dilute nitride spin-VCSEL.

We report the first room temperature optical spin-injection of a dilute nitride 1300 nm vertical-cavity surface-emitting laser (VCSEL) under continuous-wave optical pumping. We also present a novel experimental protocol for the investigation of optical spin-injection with a fiber setup. The experimental results indicate that the VCSEL polarization can be controlled by the pump polarization, and the measured behavior is in excellent agreement with theoretical predictions using the spin flip model. The ability to control the polarization of a long-wavelength VCSEL at room temperature emitting at the wavelength of 1.3 µm opens up a new exciting research avenue for novel uses in disparate fields of technology ranging from spintronics to optical telecommunication networks.

Exposure risk assessment to organic compounds based on their concentrations in return water from shale gas developments.

Because of shale gas operations, significant amounts of return water from hydraulic fracturing are stored in tanks and/or ponds on the surface. These waters contain varying concentrations of toxic organic compounds; hence, there is reasonable concern about the occurrence of hypothetical leakages, which would cause adverse environmental effects and pose a risk to human health. In this study, the chronic and acute carcinogenic and non-carcinogenic risks from exposure to these pollutants by inhalation, ingestion and dermal contact have been assessed for an affected area. The first part of this study focused on estimating the concentrations of organic compounds in the water-soil-atmosphere system. These models are of a general nature and can be applied to any site. In this study, they are applied to the Marcellus shale formation. The analyses developed in this work show that the risks - both carcinogenic and non-carcinogenic - regarding the inhalation of volatile organic compounds (VOCs) increase rapidly and exceed the acceptable thresholds by several orders of magnitude in all scenarios, irrespective of the different recharge rates considered. Given that the hypothetical leakage under consideration occurs at a depth of 50 cm, in the buried part of a semi-buried tank-type reservoir, the direct contamination via wastewater of the most superficial parts of the soil is less likely, and soil particles are generally widely dispersed in air before inhaling. Moreover, the sensitivity analysis indicated that the variable contributing the most to the determined risk levels was the pollutant concentration, followed by the exposure time. Therefore, using appropriate technology to reduce pollutant concentrations in storage ponds is the best strategy to minimise the associated risk to human health.

Ultrafast neuromorphic photonic image processing with a VCSEL neuron.

The ever-increasing demand for artificial intelligence (AI) systems is underlining a significant requirement for new, AI-optimised hardware. Neuromorphic (brain-like) processors are one highly-promising solution, with photonic-enabled realizations receiving increasing attention. Among these, approaches based upon vertical cavity surface emitting lasers (VCSELs) are attracting interest given their favourable attributes and mature technology. Here, we demonstrate a hardware-friendly neuromorphic photonic spike processor, using a single VCSEL, for all-optical image edge-feature detection. This exploits the ability of a VCSEL-based photonic neuron to integrate temporally-encoded pixel data at high speed; and fire fast (100 ps-long) optical spikes upon detecting desired image features. Furthermore, the photonic system is combined with a software-implemented spiking neural network yielding a full platform for complex image classification tasks. This work therefore highlights the potential of VCSEL-based platforms for novel, ultrafast, all-optical neuromorphic processors interfacing with current computation and communication systems for use in future light-enabled AI and computer vision functionalities.

Coarse label refinement for improving prostate cancer detection in ultrasound imaging.

PURPOSE: Ultrasound-guided biopsy plays a major role in prostate cancer (PCa) detection, yet is limited by a high rate of false negatives and low diagnostic yield of the current systematic, non-targeted approaches. Developing machine learning models for accurately identifying cancerous tissue in ultrasound would help sample tissues from regions with higher cancer likelihood. A plausible approach for this purpose is to use individual ultrasound signals corresponding to a core as inputs and consider the histopathology diagnosis for the entire core as labels. However, this introduces significant amount of label noise to training and degrades the classification performance. Previously, we suggested that histopathology-reported cancer involvement can be a reasonable approximation for the label noise. METHODS: Here, we propose an involvement-based label refinement (iLR) method to correct corrupted labels and improve cancer classification. The difference between predicted and true cancer involvements is used to guide the label refinement process. We further incorporate iLR into state-of-the-art methods for learning with noisy labels and predicting cancer involvement. RESULTS: We use 258 biopsy cores from 70 patients and demonstrate that our proposed label refinement method improves the performance of multiple noise-tolerant approaches and achieves a balanced accuracy, correlation coefficient, and mean absolute error of 76.7%, 0.68, and 12.4, respectively. CONCLUSIONS: Our key contribution is to leverage a data-centric method to deal with noisy labels using histopathology reports, and improve the performance of prostate cancer diagnosis through a hierarchical training process with label refinement.

Training deep neural networks with noisy clinical labels: toward accurate detection of prostate cancer in US data.

PURPOSE: Ultrasound is the standard-of-care to guide the systematic biopsy of the prostate. During the biopsy procedure, up to 12 biopsy cores are randomly sampled from six zones within the prostate, where the histopathology of those cores is used to determine the presence and grade of the cancer. Histopathology reports only provide statistical information on the presence of cancer and do not normally contain fine-grain information of cancer distribution within each core. This limitation hinders the development of machine learning models to detect the presence of cancer in ultrasound so that biopsy can be more targeted to highly suspicious prostate regions. METHODS: In this paper, we tackle this challenge in the form of training with noisy labels derived from histopathology. Noisy labels often result in the model overfitting to the training data, hence limiting its generalizability. To avoid overfitting, we focus on the generalization of the features of the model and present an iterative data label refinement algorithm to amend the labels gradually. We simultaneously train two classifiers, with the same structure, and automatically stop the training when we observe any sign of overfitting. Then, we use a confident learning approach to clean the data labels and continue with the training. This process is iteratively applied to the training data and labels until convergence. RESULTS: We illustrate the performance of the proposed method by classifying prostate cancer using a dataset of ultrasound images from 353 biopsy cores obtained from 90 patients. We achieve area under the curve, sensitivity, specificity, and accuracy of 0.73, 0.80, 0.63, and 0.69, respectively. CONCLUSION: Our approach is able to provide clinicians with a visualization of regions that likely contain cancerous tissue to obtain more accurate biopsy samples. The results demonstrate that our proposed method produces superior accuracy compared to the state-of-the-art methods.

Towards targeted ultrasound-guided prostate biopsy by incorporating model and label uncertainty in cancer detection.

PURPOSE: Systematic prostate biopsy is widely used for cancer diagnosis. The procedure is blind to underlying prostate tissue micro-structure; hence, it can lead to a high rate of false negatives. Development of a machine-learning model that can reliably identify suspicious cancer regions is highly desirable. However, the models proposed to-date do not consider the uncertainty present in their output or the data to benefit clinical decision making for targeting biopsy. METHODS: We propose a deep network for improved detection of prostate cancer in systematic biopsy considering both the label and model uncertainty. The architecture of our model is based on U-Net, trained with temporal enhanced ultrasound (TeUS) data. We estimate cancer detection uncertainty using test-time augmentation and test-time dropout. We then use uncertainty metrics to report the cancer probability for regions with high confidence to help the clinical decision making during the biopsy procedure. RESULTS: Experiments for prostate cancer classification includes data from 183 prostate biopsy cores of 41 patients. We achieve an area under the curve, sensitivity, specificity and balanced accuracy of 0.79, 0.78, 0.71 and 0.75, respectively. CONCLUSION: Our key contribution is to automatically estimate model and label uncertainty towards enabling targeted ultrasound-guided prostate biopsy. We anticipate that such information about uncertainty can decrease the number of unnecessary biopsy with a higher rate of cancer yield.

Optical neuron using polarisation switching in a 1550nm-VCSEL.

We report a new approach to mimic basic functionalities of a neuron using a 1550 nm Vertical Cavity Surface Emitting Laser (VCSEL) which is based on the polarisation switching (PS) that can be induced in these devices when subject to polarised optical injection. Positive and negative all-optical threshold operations are demonstrated experimentally using external optical injection into the two orthogonal polarizations of the fundamental transverse mode. The polarisation of the light emitted by the device is used to determine the state of the VCSEL-Neuron, active (orthogonal) or inactive (parallel). This approach forms a new way to reproduce optically the response of a neuron to an excitatory and an inhibitory stimulus.