Scaling Limit Research Articles

PMFSNet: Polarized multi-scale feature self-attention network for lightweight medical image segmentation.

Current state-of-the-art medical image segmentation methods prioritize precision but often at the expense of increased computational demands and larger model sizes. Applying these large-scale models to the relatively limited scale of medical image datasets tends to induce redundant computation, complicating the process without the necessary benefits. These approaches increase complexity and pose challenges for integrating and deploying lightweight models on edge devices. For instance, recent transformer-based models have excelled in 2D and 3D medical image segmentation due to their extensive receptive fields and high parameter count. However, their effectiveness comes with the risk of overfitting when applied to small datasets. It often neglects the vital inductive biases of Convolutional Neural Networks (CNNs), essential for local feature representation. In this work, we propose PMFSNet, a novel medical imaging segmentation model that effectively balances global and local feature processing while avoiding the computational redundancy typical of larger models. PMFSNet streamlines the UNet-based hierarchical structure and simplifies the self-attention mechanism's computational complexity, making it suitable for lightweight applications. It incorporates a plug-and-play PMFS block, a multi-scale feature enhancement module based on attention mechanisms, to capture long-term dependencies. The extensive comprehensive results demonstrate that our method achieves superior performance in various segmentation tasks on different data scales even with fewer than a million parameters. Results reveal that our PMFSNet achieves IoU of 84.68%, 82.02%, 78.82%, and 76.48% on public datasets of 3D CBCT Tooth, ovarian tumors ultrasound (MMOTU), skin lesions dermoscopy (ISIC 2018), and gastrointestinal polyp (Kvasir SEG), and yields DSC of 78.29%, 77.45%, and 78.04% on three retinal vessel segmentation datasets, DRIVE, STARE, and CHASE-DB1, respectively. Our proposed model exhibits competitive performance across various datasets, accomplishing this with significantly fewer model parameters and inference time, demonstrating its value in model integration and deployment. It strikes an optimal compromise between efficiency and performance and can be a highly efficient solution for medical image analysis in resource-constrained clinical environments. The source code is available at https://github.com/yykzjh/PMFSNet.

Real-life experience with disease-modifying drugs in hereditary transthyretin amyloid polyneuropathy: A clinical and electrophysiological appraisal.

New treatments have dramatically improved the prognosis for Hereditary Transthyretin Amyloid Polyneuropathy (ATTRv-PN). However, there is a lack of routine follow-up studies outside of therapeutic trials. Our aim was to report the long-term clinical and electrophysiological evolution of a cohort of ATTRv-PN patients and to determine which biomarkers are most sensitive to change. We retrospectively collected neuropathy impairment scale (NIS), polyneuropathy disability scale (PND), overall neuropathy limitation scale (ONLS), rash built overall disability scale (RODS), electrodiagnostic data, motor unit number index (MUNIX), troponin and N-terminal pro-brain natriuretic peptide levels. Electrophysiological worsening was defined as a 20% decrease in previous values. Thirty-five patients, with a median age of 58 (interquartile ranges 42-71) years, were followed for a median of 36 (24-48) months. All patients received a transthyretin stabiliser, gene silencer or liver transplant. Overall assessment of the cohort showed clinical, biological and electrophysiological stability. However, on an individual basis, NIS worsened in 45% of patients (14/31), ONLS in 46% (13/28), PND in 28% (9/32) and RODS in 39% (11/28) at the last follow-up. Motor amplitude sum score decreased in 33% (11/33), amplitude recorded on tibialis anterior muscle in 44% (12/27), sensory amplitude sum score in 39% (11/28) and MUNIX sum score in 27% (7/26). Overall effectiveness of ATTRv-PN treatments in routine care is good. However, individual assessments show up to 40% deterioration over time. Electrophysiological measures are valuable monitoring tools but are not more sensitive to change than clinical scores. Results must be confirmed in larger cohorts.

Development of a Web-Based Independent Curriculum Learning Assessment Application System for Raudhatul Athfal Teachers

This study designs a web-based application model that is able to support the Merdeka Curriculum assessment effectively and efficiently and has obtained justification from experts and been tested on a limited scale. The method used is research and development (R&D) with the Borg and Gall model, which focuses on developing the Merdeka Curriculum learning assessment application for RA teachers. This research reached the preliminary field test stage to produce an application prototype, which still requires repeated testing on a wider scale. The results of validation by material experts show that this application is very feasible for use by RA teachers, with scores of 93.3% and 90%, respectively. Validation by media experts resulted in a score of 83.3%, indicating that the app is in the feasible category but requires some improvements. The field test showed that this application is very functional and easy to use by teachers for assessment management, with a user score of 95%. Based on these results, this study successfully developed and evaluated a web-based Merdeka Curriculum assessment application that is effective and in accordance with the needs of teachers in Raudhatul Athfal.

Strong Markov Dissipation in Driven-Dissipative Quantum Systems

The Lindblad equation, which describes Markovian quantum dynamics under dissipation, is usually derived under the weak system-bath coupling assumption. Strong system-bath coupling often leads to non-Markov evolution. The singular-coupling limit is known as an exception: it yields a Lindblad equation with an arbitrary strength of dissipation. However, the singular-coupling limit requires high-temperature limit of the bath, and hence the system ends up in a trivial infinite-temperature state, which is not desirable in the context of quantum control. In this work, it is shown that we can derive a Markovian Lindblad equation for an arbitrary strength of the system-bath coupling by considering a new scaling limit that is called the singular-driving limit, which combines the singular-coupling limit and fast periodic driving. In contrast to the standard singular-coupling limit, an interplay between dissipation and periodic driving results in a nontrivial steady state.

Performance Assessment of Ultrascaled Vacuum Gate Dielectric MoS2 Field-Effect Transistors: Avoiding Oxide Instabilities in Radiation Environments.

Gate dielectrics are essential components in nanoscale field-effect transistors (FETs), but they often face significant instabilities when exposed to harsh environments, such as radioactive conditions, leading to unreliable device performance. In this paper, we evaluate the performance of ultrascaled transition metal dichalcogenide (TMD) FETs equipped with vacuum gate dielectric (VGD) as a means to circumvent oxide-related instabilities. The nanodevice is computationally assessed using a quantum simulation approach based on the self-consistent solutions of the Poisson equation and the quantum transport equation under the ballistic transport regime. The performance evaluation includes analysis of the transfer characteristics, subthreshold swing, on-state and off-state currents, current ratio, and scaling limits. Simulation results demonstrate that the investigated VGD TMD FET, featuring a gate-all-around (GAA) configuration, a TMD-based channel, and a thin vacuum gate dielectric, collectively compensates for the low dielectric constant of the VGD, enabling exceptional electrostatic control. This combination ensures superior switching performance in the ultrascaled regime, achieving a high current ratio and steep subthreshold characteristics. These findings position the GAA-VGD TMD FET as a promising candidate for advanced radiation-hardened nanoelectronics.

Development of Modified E-Modules Augmented Reality Android Based to Improve Student’s Interest and Learning Outcomes

Scientific and technical advancements have intensified efforts to incorporate technological results into the teaching and learning process. As a result, new advancements in learning systems are required, such as the creation of Augmented Reality-based e-modules. In colloidal material research, Augmented Reality on an Android tablet is employed in modified Chemistry E-modules to increase student engagement and learning outcomes. The objectives of this research are to create e-modules, evaluate their use, and analyze the impact of chemistry e-modules on learning outcomes and student participation. The feasibility of e-modules is determined through the validation test of 9 validators consisting of media experts, linguists and teaching practitioners. While the e-module was tested on 3 scales, namely limited scale, medium scale and wide scale on respondents, namely grade XI students at SMA Islam Terpadu Baitul Muslim, SMA Teladan, SMA TQ Al Mannan in East Lampung Regency. Based on the research, the academic results and attention spans of grade XI pupils are impacted by chemistry e-modules with customized Augmented Reality on colloid material, A 0.005 significance level has been set. Furthermore, the N-gain value indicates a difference in the attention and learning outcomes of grade XI pupils before and after utilizing the program. Students who do not study the material through e-modules have N-gain values in the low category, while students who study the material through e-modules have N-gain in the high category. In the validation test by validators, it is known that the Aiken coefficient value (V-count) is greater than 0.8 with a very good Likert scale interpretation.

Unlocking quantum SVM potential: optimal feature map generation and feature selection

Abstract The study proposes a mechanism to generate effective feature maps with optimal feature selection using the Tabu Search algorithm. It compares the performance of classical support vector machines (SVM), quantum support vector machines (QSVM) with only gate selection, and QSVM with both gate selection and feature selection (QSVM-FS) across various datasets. The results indicate that classical SVMs excel with several benchmark datasets, while QSVMs show superior performance on synthetic datasets with non-linear separability. Notably, QSVM-FS consistently outperforms QSVM without feature selection, highlighting the importance of feature selection in enhancing model accuracy. These findings suggest that while both quantum and classical SVMs have unique advantages, quantum methods offer particular benefits in specific scenarios. In the NISQ era, classical simulations are a primary tool for assessing quantum experiments, though they face challenges such as design impacts, limited scales, and biases. Ultimately, no definitive winner exists between quantum and classical methods, as both have their own strengths.

Clinical Outcome Assessments and Biomarkers in Charcot-Marie-Tooth Disease.

Charcot-Marie-Tooth disease (CMT) encompasses a diverse group of genetic forms of inherited peripheral neuropathy and stands as the most common hereditary neurologic disease worldwide. At present, no disease-modifying treatments exist for any form of CMT. However, promising therapeutic strategies are rapidly emerging, necessitating careful consideration of clinical outcome assessments (COAs) and clinical trial design. In this review, we discuss the challenges and successes over the past 2 decades in efforts to design and validate COAs and disease biomarkers of CMT. Natural history studies and completed clinical trials have underscored the limitations of early clinical scales for CMT, including the neuropathy impairment score, overall neuropathy limitation scale, and CMT neuropathy score. These studies prompted the development of newer, psychometrically supported scales including the CMT neuropathy score version 2, CMT pediatric scale, CMT infant scale, CMT functional outcome measure, and CMT health index. Although promising, many of these scales have yet to be formally tested in longitudinal studies. Given inherent challenges of relying solely on COAs in slowly progressive forms of CMT, there is growing recognition of the need for objective disease biomarkers that could serve as surrogate end points in clinical trials. Among these, MRI muscle fat fraction in the lower extremities has proven the most responsive biomarker to date, although its relationship to functional outcomes and its performance in treatment trials remain uncertain. Serum biomarkers including neurofilament light, transmembrane protease serine 5, specific microRNAs, neural cell adhesion molecule 1, and growth and differentiation factor 15 reliably distinguish patients with CMT from controls, but their responsiveness to effective therapies also remains unknown. Although the optimal combination of outcome measures in CMT has yet to be established, many of the most promising COAs and biomarkers are now being put to the test in ongoing clinical trials. These early studies will also help address other critical clinical trial considerations, such as patient selection and enrollment targets, which will become increasingly important in this exciting new era of bringing the first disease-modifying treatments to people living with CMT.

Development of agricultural insurance in Ukraine

Agricultural insurance in Ukraine remains underdeveloped, characterized by fragmented progress and significant reliance on state support, necessitating a systematic, research-based approach for its advancement. The study evaluates the sector’s development from 2014 to 2023, employing general scientific methods of cognition. Abstract and logical methods were applied to summarize results and formulate conclusions, while comparative analysis facilitated the assessment of key trends. Graphical techniques were employed to enhance the visualization of data obtained. A monographic approach was adopted to conduct an in-depth analysis of parametric insurance, complemented by a critical review of the legal framework to evaluate its influence on the sector’s development.The study reveals the limited scale of agricultural insurance relative to the agro-industrial sector’s growth, with only 3% of agricultural areas insured and agricultural insurance comprising 2% of insurers’ portfolios. The average claims payout rate is 50%, with reinsurance levels at 60%. The sector’s insurance products are categorized into two main types: classical and parametric. Parametric, index-based insurance demonstrates superior efficiency, achieving a claims ratio of 35% compared to 14% for classical models.External challenges, including the COVID-19 pandemic, regulatory changes, and Russia’s military aggression, have further impeded the sector’s progress. Despite these obstacles, the study identifies promising pathways for development. These include fostering social responsibility among stakeholders, integrating digital technologies, and implementing innovative approaches to insurance practices.The study underscores the necessity to address systemic inefficiencies, adopt tailored strategies, and align insurance practices with Ukraine’s agro-industrial sector’s unique needs to enhance resilience and promote sustainable development.

Designing microplastic-binding peptides with a variational quantum circuit-based hybrid quantum-classical approach.

De novo peptide design exhibits great potential in materials engineering, particularly for the use of plastic-binding peptides to help remediate microplastic pollution. There are no known peptide binders for many plastics-a gap that can be filled with de novo design. Current computational methods for peptide design exhibit limitations in sampling and scaling that could be addressed with quantum computing. Hybrid quantum-classical methods can leverage complementary strengths of near-term quantum algorithms and classical techniques for complex tasks like peptide design. This work introduces a hybrid quantum-classical generative framework for designing plastic-binding peptides combining variational quantum circuits with a variational autoencoder network. We demonstrate the framework's effectiveness in generating peptide candidates, evaluate its efficiency for property-oriented design, and validate the candidates with molecular dynamics simulations. This quantum computing-based approach could accelerate the development of biomolecular tools for environmental and biomedical applications while advancing the study of biomolecular systems through quantum technologies.

Harmonic balls in Liouville quantum gravity

AbstractHarmonic balls are domains that satisfy the mean‐value property for harmonic functions. We establish the existence and uniqueness of harmonic balls on Liouville quantum gravity (LQG) surfaces using the obstacle problem formulation of Hele–Shaw flow. We show that LQG harmonic balls are neither Lipschitz domains nor LQG metric balls, and that the boundaries of their complementary connected components are Jordan curves. We conjecture that LQG harmonic balls are the scaling limit of internal diffusion limited aggregation on random planar maps. In a companion paper, we prove this in the special case of mated‐CRT maps.

The development of transfer technologies for advanced 2D circuits integration

AbstractIn the light of the scaling limitations of conventional CMOS technology, two‐dimensional (2D) materials offer a transformative avenue for advancing Moore's law in the post‐Moore era. The technology for transferring 2D materials serves as a crucial link between their synthesis and device integration. This review provides a comprehensive assessment of advancements in the transfer technologies and integration of 2D materials, which are essential for next‐generation electronics. Firstly, state‐of‐the‐art methodologies for high‐quality, wafer‐scale transfer of 2D materials, including both wet and dry transfer methods are thoroughly reviewed. And the requirements for massive transfer of 2D materials compatible with silicon line while preserving their intrinsic properties are disscussed. Next, we focus on 2D integration techniques, paying special attention to the construction of van der Waals contacts at the 2D material/dielectric interface and 2D material/metal electrode interface. Finally, the potential for layer‐by‐layer or tier‐by‐tier transfer 2D devices for monolithic 3D integration was also discussed. This review concludes by highlighting the significant challenges that remain in leveraging the potential of 2D materials at the circuit and system levels, proposing forward‐looking development in transfer strategies.

Harm Reduction: The Neglected Pillar of US Drug Policy.

Harm reduction programs provide tools that enable people who use drugs to do so more safely in a nonstigmatizing environment without the goal of them necessarily seeking treatment or abstinence. Most harm reduction programs in the United States distribute sterile syringes and naloxone and safely dispose of used syringes and other drug use supplies. Many also provide drug checking services, and other safer use supplies. These programs exist on a limited scale and often face restrictions on their funding and scope of operations. While research demonstrates the effectiveness of existing programs in preventing infectious disease transmission and fatal overdose, there is less evidence about conditions that support the effective expansion and sustainment of existing models. Other harm reduction interventions such as overdose prevention centers and safer supply programs have promising international evidence but are prohibited or severely restricted under US law. In this review, we summarize the evidence for harm reduction interventions, describe the policy environment in which they exist, and provide recommendations to better align drug policy with existing and emerging evidence in the US context.

Nerve ultrasound helps to distinguish CIDP patients with diabetes from patients with diabetic polyneuropathy

Diabetic polyneuropathy (DPN) shares overlapping clinical and electrodiagnostic features with chronic inflammatory demyelinating polyneuropathy (CIDP), which complicates the differential diagnosis of CIDP in diabetic patients. 32 patients with diabetes mellitus and CIDP, 68 patients with CIDP without diabetes, 83 patients with DPN, and 28 diabetic patients without polyneuropathy were examined using clinical scores (Overall Neuropathy Limitation Scale (ONLS), Neuropathy Symptom Score, Neuropathy Deficit Score), nerve conduction studies, and nerve ultrasound (Ultrasound Pattern Sum Score (UPSS)). The ONLS was significantly higher in the CIDP patients with diabetes than in DPN (median [interquartile range]: 4.0 [3.0] vs. 0 [1.0], p < 0.001) as well as the UPSS (4.0 [6.0] vs. 0 [2.9], p < 0.001). Multiple binary logistic regression revealed UPSS and ONLS as statistically significant predictors to differentiate between CIDP with diabetes and DPN. Receiver operating characteristic curve analysis showed the ONLS with an area under the curve (AUC) of 0.918 (95% CI: 0.868-0.0.967, p < 0.001). The UPSS total score had an AUC of 0.826 (95% CI: 0.743–0.909, p < 0.001). An UPSS ≥ 2.5 had a sensitivity of 77.4% and a specificity of 68.7% to detect CIDP. An ONLS ≥ 1.5 had a sensitivity of 87.1% and a specificity of 81.9% to detect CIDP. ROC curve analysis of a composite score of ONLS and UPSS revealed an AUC of 0.959 (95% CI: 0.928–0.991, p < 0.001). CIDP is an important differential diagnosis in people with diabetes mellitus. This study reports that the UPSS is well suited to differentiate between DPN and CIDP.

Off-Stoichiometry Thiol-Ene Surface Functionalization: Example with Gold Nanoparticles.

Surface modification is essential in microfluidic applications due to the inherent hydrophobicity of polymers, which can lead to biofouling and reagent denaturation. Despite the development, challenges such as hydrophobic molecule absorption and limitations in scaling are still present. Off-stoichiometry thiol-ene (OSTE) materials have emerged as a promising alternative, offering advantages like rapid prototyping, minimal hydrophobic absorption, and customizable surface chemistries. While the thiol-ene polymerization mechanism is well understood, the fundamental understanding of thiol group binding on OSTE surfaces remains limited. Existing techniques to analyze surface groups lack the capability to confirm the stable presence of thiol groups on the surface. In our study, using Raman and X-ray photoelectron spectroscopy techniques, we investigated a potential method for enhancing the surface properties of OSTE polymer-the attachment of novel linkers to the surface. We have demonstrated our synthesized compound efficiency by binding gold nanoparticles to the OSTE surface. Our findings indicate that chemical reactions involving double bonds with the material surface hold the most potential for effective surface modification for gold binding.

ЭТНОНАЦИОНАЛЬНАЯ СИТУАЦИЯ ИРАНА: ИДЕОЛОГИЧЕСКИЕ И НАУЧНЫЕ ПОДХОДЫ

The article examines the ethno-national situation in contemporary Iran. The author, presenting a thesis on the existence of ideological and scientific approaches to the issue, analyzes the history, ethnic structure, anthropological and linguistic identity, and, most importantly, the political relationships among Iranian peoples, drawing relevant conclusions. The first section details the attempts by ideologists seeking to exploit the current ethno-national situation in Iran, showing the increasing attention of international and regional organizations, both large and small, from distant and neighboring countries, to national relations and the ethno-national situation in Iran, emphasizing their different approaches to this issue. The multinational nature of the Islamic Republic of Iran is also noted, as well as the fundamental constancy of the state’s national policy and the variations in its manifestations. In the subsequent presentation of the material, the article highlights the unique aspects of internal and external attitudes toward the national situation in Iran and emphasizes that the problem under study, according to specific parameters, is associated not only with internal but also with regional and, to some extent, global security. The article provides a relatively detailed analysis of the works of Iranian authors who adhere to an objective, scientific approach to all issues related to the ethno-national situation in the Islamic Republic of Iran. The study concludes that, alongside the long-standing dominant ideological approach aimed at denying the existence of ethnic structures and national relations, as well as justifying the state policy of creating a nation-state, in recent years, and on a limited scale, the formation of an objective and scientific approach has begun, emphasizing the existence of an ethnic structure, a crisis in national relations, and the need for reform in national policy. The article’s conclusions stress the necessity of adhering to the principles of international law in the area of human rights, including the collective rights of people (ethnic and religious minorities), as well as ensuring the implementation of the rights provided in the relevant articles of Iran’s constitution.

Rahvapsühholoogia ajalised piirid / Temporal Limits of Folk Psychology

Teesid: Kas meie igapäevane raamistik vaimunähtuste tähistamiseks ehk rahvapsühholoogia rakendub ajaliste piiranguteta? Või ei rakendu rahvapsühholoogia mikroskaalal (millisekunditest kuni sadade millisekunditeni). Käesolev artikkel vaeb seda küsimust ja uurib, et mis järeldub sellest vaimsete nähtuste olemuse kohta, kui rahvapsühholoogia mikroskaalal ei rakendu. Vaatluse alla tuleb eeldus, mille kohaselt vaimseid seisundeid individueeritakse rahvapsühholoogia kaudu. Toon välja mitmesuguseid võimalusi käsitada rahvapsühholoogia, mikroskaala ja mentaalse omavahelist seost. It has been claimed that familiar psychological categories do not apply at a very short time scale. The conceptual framework that collects our everyday psychological notions is called ‘folk psychology’. This paper explores the following question: is there a limited time scale in which folk psychology is applicable, and if that is the case, then what does this tell us about the nature of mental phenomena? In particular, the question concerns the applicability of folk psychology at the microscale (ranging from milliseconds up to hundreds of milliseconds). I outline several options concerning the relationship between folk psychology, the microscale and the mental. Why does this matter? First, this is important since if folk psychology applies only within certain temporal limits, this is an obstacle to developing models of micro-scale time consciousness in folk-psychological terms. Second, ‘folk psychology’ can be understood as just another name for a set of mental terms. This is not an innocent assumption. If this assumption holds, then the folk conception tacitly settles which properties are mental. We can call this assumption the ‘Principle of Folk Individuation’ (FIP): mental states are individuated only through folk psychology. If folk psychology is limited to a macroscale, and the FIP holds, then processes happening outside this scale at the millisecond range are not mental. This presumes that the mental is recognition-dependent: a property is mental only if it has a specification in mental (folk) terms; if it lacks it, there is no reason to classify it as mental. On the other hand, if folk psychology is limited to the macroscale, but there are good reasons to think that the mind is not, then this tells against the Folk Individuation Principle. Some reasons for considering certain events at the microscale as mental, albeit not part of folk psychology, could be found in research in psychology, where scientists have ascertained certain modality-dependent thresholds for distinguishing stimuli. The lowest threshold is for auditory stimuli (only a two-ms interval between stimuli suffices to detect them as separate). The ordering of stimuli requires intervals between stimuli of at least 20 ms. Are these discriminations mental? Prima facie, they must be, for these are conscious events. Therefore, they provide a counterexample to the FIP. This would lead to the position that the microscale processes are mental. At this point, someone who would like to keep the FIP might argue that considerations based on temporal thresholds do not show that the microscale events are mental but not folk-psychological. First, one could hold that these short-lived conscious experiences are neural states and that the brain has better temporal resolution than the mind/folk psychology. However, this reply might cause difficulties in giving a full picture of how neural consciousness relates to mental events. If microscale conscious events are merely neural, one is faced with the task of explaining at what point a conscious event becomes properly mental. The second option is to point out that ‘conscious experience’ is a folk-psychological term, too. Hence, considerations from temporal thresholds do not tell against the FIP. However, one may ask if the term ‘experience’ applies without problems to these discriminatory states. For instance, how can we tell that these states are perceptual experiences, not recent memories? There is another option. There is no need to construe folk psychology narrowly as a theory of beliefs, desires, memories and thoughts. In principle, folk psychology can be extended and developed: it could also include reference to events that take place at the microscale. We would need a new vocabulary to characterise those states, but this new vocabulary could still be part of an extended folk psychology—folk psychology 2.0. In this way, we could keep the FIP by updating it to state that mental states are individuated only through folk psychology 2.0 (which includes folk psychology and more). Then, one could say that although folk psychology, as traditionally conceived, applies only at the macroscale, folk psychology 2.0 also spans the microscale.

Developing, Characterizing, and Modeling CRISPR-Based Point-of-Use Pathogen Diagnostics.

Recent years have seen intense interest in the development of point-of-care nucleic acid diagnostic technologies to address the scaling limitations of laboratory-based approaches. Chief among these are combinations of isothermal amplification approaches with CRISPR-based detection and readouts of target products. Here, we contribute to the growing body of rapid, programmable point-of-care pathogen tests by developing and optimizing a one-pot NASBA-Cas13a nucleic acid detection assay. This test uses the isothermal amplification technique NASBA to amplify target viral nucleic acids, followed by the Cas13a-based detection of amplified sequences. We first demonstrate an in-house formulation of NASBA that enables the optimization of individual NASBA components. We then present design rules for NASBA primer sets and LbuCas13a guide RNAs for the fast and sensitive detection of SARS-CoV-2 viral RNA fragments, resulting in 20-200 aM sensitivity. Finally, we explore the combination of high-throughput assay condition screening with mechanistic ordinary differential equation modeling of the reaction scheme to gain a deeper understanding of the NASBA-Cas13a system. This work presents a framework for developing a mechanistic understanding of reaction performance and optimization that uses both experiments and modeling, which we anticipate will be useful in developing future nucleic acid detection technologies.

Modeling memory function of entangled photon and classical laser photon-count fluctuations using white noise integral analysis

Abstract This study investigates photon-count fluctuation dynamics of two light sources, namely a spontaneous parametric down-conversion (SPDC) light source and a 780 nm attenuated laser diode (LD). White noise integral with customizable memory function is used to model the mean square displacements (MSDs) and the probability density functions (PDFs) for both light sources. This approach overcomes the limitation of monofractal scaling of fractional Brownian motion (fBm) model characterized by a single Hurst exponent. The memory function used has an exponential-tempered power-law relation, parametrized by μ and β, where β modulates the extent of memory parameter μ. Although optical losses and detector inefficiencies degrade photon statistics to Poissonian at post-detection, our findings reveal notable memory effects at higher mean photon counts, especially in the SPDC source with memory parameter μ ≧ 1.00, compared to the classical LD, which remained relatively constant at μ ≦ 1.00. Both light sources shared similar correction parameters β, which indicates they have identical photon-count fluctuations at short time but diverge significantly at longer time. This work highlights the need for models beyond fBm, capable of capturing complex MSD behaviors of photon-count fluctuations.

Monitoring subseafloor temperature and fluid pressure in sealed ODP/IODP boreholes to constrain in-situ hydrological state and processes in igneous oceanic crust

We review the contributions to our understanding of the hydrogeology of the oceanic crust as gained by monitoring subseafloor temperatures and pressures in CORK (“Circulation Obviation Retrofit Kit”) sealed hole observatories that penetrate through marine sediments into igneous basement. CORKs were installed during 1991-2012 in 17 holes drilled by the Ocean Drilling Program (ODP) and Integrated Ocean Drilling Programs (IODP) in igneous oceanic crust (aged 0.4 to 24 Ma) in the thickly sedimented eastern Pacific Ocean and in the thinly sedimented north Atlantic Ocean. Results indicate that the igneous crust in all these settings is highly transmissive and supports vigorous lateral fluid flow and/or convection beneath the sediment cover driven by very small horizontal pressure gradients. Inter-CORK experiments suggest that the horizontal permeability of the young oceanic basement at these sites may be anisotropic, with higher values in the direction parallel to the axis of spreading and tectonic fabric and lower values in a ridge-normal cross-strike direction. Tracer experiments applied to ridge-parallel flow suggest that only a small fraction of the crust is well connected. CORKs also record the response of subseafloor formation fluid pressures to seafloor tidal loading, and, once the tidal responses are filtered out, response to tectonic strain events. Interpretations based on these responses and original two-dimensional modelling of ridge-normal fluid circulation in the crust suggest a scale dependence of permeability of igneous oceanic crust (higher values at larger scales up to tens of km), although recent three-dimensional models suggest a more limited scale effect. CORKs have also provided important geochemical and microbiological results from the igneous oceanic crust, although they are not reviewed in this paper.