High-level Specification Research Articles

Two-step-7-Pink Rule: A Practical Tool for the Dermoscopic Evaluation of Fully Amelanotic Skin Lesions

Introduction: The diagnosis of fully amelanotic skin tumors is difficult on clinical and dermoscopic examination. Objective: We sought to identify an accurate and user-friendly dermoscopic algorithm to differentiate between benign and malignant pink lesions. Methods: The database of 1 referral center was retrospectively reviewed for images of non-inflammatory fully amelanotic skin lesions. Two dermatologists jointly assessed a validation set of images for dermoscopic criteria and constructed a diagnostic algorithm, the 2-step 7-pink rule (2S-7PR). Two external clinicians, with different skills in dermoscopy and blinded to the final diagnosis, separately evaluated images from the validation test sets using the prevalent criterion method and the new 2S-7PR algorithm. Results: A total of 763 lesions from 652 patients were included in the validation set database, of which 68.3% were malignant and 31.7% were benign. Three suspicious dermoscopic criteria were included in the first step of the 2S-7PR: polymorphous or sharply focused vessels, scales or crusts, and erosions or ulcerations; and 4 non-suspicious criteria were included in the second: white collarette, white scar-like area, vascular lacunae, and necklace pinpoint vessels. High levels of specificity and sensitivity were calculated in the validation and test phases for both the expert and non-expert evaluators, the former achieving higher levels of both sensitivity and specificity by employing the 2S-7PR compared to the prevalent method, and the latter only improved specificity. Conclusions: The present study showed that an algorithm focused on a few reproducible and easily recognizable criteria could improve diagnostic accuracy in the management of amelanotic lesions.

Detection of Toxoplasma gondii in Brain Tissues of Pet Birds with Neurological Symptoms Using Loop-Mediated Isothermal Amplification (LAMP) and PCR.

This study seeks to close this divide by assessing the occurrence of Toxoplasma gondii (T. gondii) in the brain tissues of pet birds displaying neurological symptoms, utilizing Nested Polymerase Chain Reaction (PCR) and Loop-mediated Isothermal Amplification (LAMP) methods. Furthermore, it aims to evaluate and contrast the sensitivity and specificity of different diagnostic procedures. Seventy bird samples, consisting of 50 sick and 20 asymptomatic samples, were assessed using various methods. Brain tissue DNA was isolated and then analyzed using nested PCR and LAMP assays targeting the T. gondii B1 gene and RE gene. Sensitivity and specificity assessments were conducted, and statistical evaluations were made using SPSS software. Our findings revealed that no T. gondii cysts were detected in the smear preparations. However, T. gondii DNA was found in 6% of the sick birds using nested PCR, and LAMP identified T. gondii DNA in 8% of these individuals. Both techniques demonstrated a high level of specificity, with LAMP showing higher sensitivity and faster processing times than nested PCR. These results significantly contribute to our understanding of toxoplasmosis and highlight the reliability and potential for the widespread use of these diagnostic techniques, providing reassurance and confidence in their effectiveness. The study underscores the importance of molecular diagnostics in promptly identifying and treating toxoplasmosis in birds. This enhances our understanding and control of the disease and underscores the significant impact of this research. The potential for further studies using more extensive and diverse bird populations to enhance surveillance and prevention strategies against T. gondii infections is promising. It should be actively pursued, giving us hope for a better future in avian health.

Echocardiographic predictors of surgical outcomes in pulmonary atresia with intact ventricular septum and development of a discriminatory calculator: an Australian tertiary institution experience.

Pulmonary atresia with intact ventricular septum is a rare congenital cardiac lesion with significant anatomical heterogeneity. Surgical planning of borderline cases remains challenging and is primarily based on echocardiography. The aim was to identify echocardiographic parameters that correlate with surgical outcome and to develop a discriminatory calculator. Retrospective review of all pulmonary atresia with intact ventricular septum cases at a statewide tertiary paediatric cardiac centre was performed between 2004 and 2020. Demographic, clinical, and echocardiographic data were collected. Logistic regression was used to develop a discriminatory tool for prediction of biventricular repair. Forty patients were included. Overall mortality was 27.5% (n = 11) and confined to patients managed as univentricular (11 vs 0, p = 0.027). Patients who underwent univentricular palliation were more likely to have an associated coronary artery abnormality (17 vs 3, p = 0.001). Fifteen surviving patients (51.7%) achieved biventricular circulation while 14 (48.3%) required one-and-a-half or univentricular palliation. Nineteen patients (47.5%) underwent percutaneous pulmonary valve perforation. No patients without tricuspid regurgitation achieved biventricular repair. The combination of tricuspid valve/mitral valve annulus dimension ratio and right ventricle/left ventricle length ratio identified biventricular management with a sensitivity of 93% and specificity of 96%. An online calculator has been made available. Pulmonary atresia with intact ventricular septum is a challenging condition with significant early and interstage morbidity and mortality risk. Patient outcomes were comparable to internationally reported data. Right ventricle/left ventricle length and tricuspid valve/mitral valve annulus dimension ratios identified a biventricular pathway with a high level of sensitivity and specificity. Absent tricuspid regurgitation was associated with a univentricular outcome.

Translation of Temporal Logic for Efficient Infinite-State Reactive Synthesis

Infinite-state reactive synthesis has attracted significant attention in recent years, which has led to the emergence of novel symbolic techniques for solving infinite-state games. Temporal logics featuring variables over infinite domains offer an expressive high-level specification language for infinite-state reactive systems. Currently, the only way to translate these temporal logics into symbolic games is by naively encoding the specification to use techniques designed for the Boolean case. An inherent limitation of this approach is that it results in games in which the semantic structure of the temporal and first-order constraints present in the formula is lost. There is a clear need for techniques that leverage this information in the translation process to speed up solving the generated games. In this work, we propose the first approach that addresses this gap. Our technique constructs a monitor incorporating first-order and temporal reasoning at the formula level, enriching the constructed game with semantic information that leads to more efficient solving. We demonstrate that thanks to this, our method outperforms the state-of-the-art techniques across a range of benchmarks.

Automated Program Refinement: Guide and Verify Code Large Language Model with Refinement Calculus

Recently, the rise of code-centric Large Language Models (LLMs) has reshaped the software engineering world with low-barrier tools like Copilot that can easily generate code. However, there is no correctness guarantee for the code generated by LLMs, which suffer from the hallucination problem, and their output is fraught with risks. Besides, the end-to-end process from specification to code through LLMs is a non-transparent and uncontrolled black box. This opacity makes it difficult for users to understand and trust the generated code. Addressing these challenges is both necessary and critical. In contrast, program refinement transforms high-level specification statements into executable code while preserving correctness. Traditional tools for program refinement are primarily designed for formal methods experts and lack automation and extensibility. We apply program refinement to guide LLM and validate the LLM-generated code while transforming refinement into a more accessible and flexible framework. To initiate this vision, we propose Refine4LLM, an approach that aims to: (1) Formally refine the specifications, (2) Automatically prompt and guide the LLM using refinement calculus, (3) Interact with the LLM to generate the code, (4) Verify that the generated code satisfies the constraints, thus guaranteeing its correctness, (5) Learn and build more advanced refinement laws to extend the refinement calculus. We evaluated Refine4LLM against the state-of-the-art baselines on program refinement and LLMs benchmarks.The experiment results show that Refine4LLM can efficiently generate more robust code and reduce the time for refinement and verification.

Home Respiratory Polygraphy to Detect Obstructive Sleep Apnea Syndrome after Supracricoid Partial Laryngectomy.

Introduction Supracricoid partial laryngectomy is a surgical treatment for advanced laryngeal cancer which is implemented to preserve organ function, but it may cause obstructive sleep apnea syndrome (OSAS) due to anatomical changes after surgery that may be neglected by clinicians. Although the gold standard for the diagnosis of OSAS is polysomnography, respiratory polygraphy is an alternative valid method with a high level of diagnostic sensitivity and specificity; since the equipment is portable, it can be used at home, with no need for hospitalization. Objective To describe the polygraphy result of patients submitted to supracricoid partial laryngectomy. Methods The present study included 13 patients, and we collected data on age, date of the surgery, body mass index, cardiovascular risk factors, Epworth score, and apnea-hypopnea index (AHI). Results The 13 patients were all male, with a mean age of 62 years. As for the AHI, one patient was classified as severe, six, as moderate, and three patients, as mild; moreover, 3 patients were simple snorers. While 77% of the sample presented OSAS, only 23% presented symptoms of drowsiness. Conclusion The study group, who underwent supracricoid partial laryngectomy, did not present self-reported symptoms of OSAS. Nevertheless, polygraphy was a useful tool in this group, and we recommend its systematic use after decannulation to avoid leaving OSAS undiagnosed. Level of evidence 4; case series study.

Web framework for the operational planning management system

In a previous research work, the authors designed an information management model for short-term planning for the Hidalgo Technological Universities; This article presents the implementation of these model in the form of a Web application based on the Controller View Model pattern that allows linking the allocation of resources for operational planning with the objectives of strategic planning at the institutional, state and federal level. The Scrum methodology was used for the development of the application in which 61 user stories and 20 Sprints were established, the application was subjected to unit and functionality testing. The framework used was Laravel. The contribution is an information management system that meets the needs in terms of Operational Planning at a higher level of specificity and security; capable of linking institutional, state and federal planning, allowing compliance with strategic planning.

Binding mode–guided development of high-performance antibodies targeting site-specific posttranslational modifications

Posttranslational modifications (PTMs) of proteins play critical roles in regulating many cellular events. Antibodies targeting site-specific PTMs are essential tools for detecting and enriching PTMs at sites of interest. However, fundamental difficulties in molecular recognition of both PTM and surrounding peptide sequence have hindered the efficient generation of highly sequence-specific anti-PTM antibodies. Furthermore, the widespread use of potentially inconsistent, nonrenewable, and molecularly undefined antibodies presents experimental challenges thought to contribute to the reproducibility problem in biomedical research. In this study, we describe the binding mode-guided development of a platform that efficiently generates potent and selective recombinant antibodies to PTMs that are molecularly defined and renewable. Our platform is built on our previous discovery of an unconventional binding mode of anti-PTM antibodies, antigen clasping, where two antigen binding sites cooperatively sandwich a single antigen, creating extensive interactions with the antigen and leading to high selectivity and potency. We designed the platform that generates clasping antibodies with two distinct binding units, resulting in efficient generation of antibodies to a set of trimethylated histone H3 with high levels of specificity and affinity. Performance comparison in chromatin immunoprecipitation, a common application in epigenomics, revealed that a clasping antibody to trimethylated histone H3 at lysine 27 exhibited superior specificity to a widely used conventional antibody and captured symmetric and asymmetric nucleosomes in a less biased manner. We further generated clasping antibodies to phosphotyrosine antigens by using the same principle. These results suggest the broad applicability of our platform to generating high-performance clasping antibodies to diverse PTMs.

Handling complexity of large high-level specifications in simulation environment: the case of transformational model-battle management

Modeling system requirements at a high level can significantly facilitate the communication of mental models across highly heterogeneous entities. Two major challenges may arise during such a process. The first is the degree to which details of the higher-level specifications can capture and effectively handle. Especially, when the model contains more nuanced descriptions of parallel execution and temporal pacing. The second challenge arises when realizing such specifications downstream due to ambiguities and incompleteness encountered in higher-level semiformal artifacts. We propose a formal specification and transformation of higher-level artifacts, particularly in the operational activity model of the Department of Defense Architecture Framework (OV-5 DoDAF). We create an isomorphic activity model corresponding to each activity in the Transformational Model-Battle Management. Then, we generate a code for simulating the models as Markov Discrete Event System Specifications. We demonstrate the size and other aspects of the experiments that can be conducted based on the generated simulation and the level of complexity in such an approach. We highlight aspects of managing complexity using model transformations and code generation techniques in a full-cycle model-based system engineering approach, expediting the process toward arriving at the concrete realization of simulation models that only originated from minimal high-level metamodels and artifacts.

Engineered CRISPR-Base Editors as a Permanent Treatment for Familial Dysautonomia.

Familial dysautonomia (FD) is a fatal inherited congenital neuropathy characterized by both progressive neurological symptoms and systemic abnormalities, and patients have a reduced life expectancy. FD is caused by a T-to-C mutation in intron 20 of the Elongator acetyltransferase complex subunit 1 ( ELP1 ) gene, which affects the ELP1 splicing process by causing tissue-specific skipping of exon 20. Here, we developed a CRISPR base editor (BE) approach capable of precisely correct this mutation. Using Cas9 variants and screening multiple gRNAs, we selected an optimized BE combination that was able to promote up to 70% on-target editing in HEK293T cells harboring the ELP1 T-to-C mutation. These editing levels were sufficient to rescue more than 50% of ELP1 transcripts with precise exon 20 inclusion. Moreover, an engineered dual intein-split system was optimized to deliver these constructs in vivo . We packaged these novel constructs in adeno-associated virus (AAV) vectors for further testing in iPSC-derived sympathetic neurons and a mouse model harboring the human ELP1 T6C gene. Our strategy could effectively correct the ELP1 splicing defects in vivo and culminated in phenotypic recovery in human neurons. Minimal off-target editing was observed demonstrating high levels of specificity with these optimized base editors. Therefore, we engineered and validated novel base editor approaches to correct the ELP1 TC6 mutation and ELP1 splicing defect and provided essential proof of concept data towards a permanent treatment for FD.

Evaluation of Immunoglobulin A Enzyme Immunoassays to Detect Primary Respiratory Syncytial Virus Infection in Infants and Young Children.

Respiratory syncytial virus (RSV) is a leading cause of acute lower respiratory infections in children <2 years of age. Prior infection in a child is usually determined by RSV antibodies; however, in young children, persisting maternal immunoglobulin G antibodies can incorrectly indicate past RSV infection. We developed and evaluated 4 immunoglobulin A (IgA) antibody enzyme immunoassays (EIAs) with the RSV F, subgroup G (Ga or Gb proteins) or RSV lysate antigens to distinguish infection induced from persisting maternal RSV antibodies. We tested the EIAs against 62 cord blood specimens (group A), 39 plasma specimens from infants not exposed to an RSV season (group B), 102 plasma specimens from infants with a documented RSV infection (group C), and 124 plasma specimens from infants exposed to their first RSV season but without a documented RSV infection (group D). Among the 2 negative control groups, no group A specimens and 1 of the group B specimens were positive in all 4 IgA EIAs, giving a specificity of 100% and 97%, respectively. The sensitivity of the F, Ga, Gb, and Lysate IgA EIAs were 88%, 31%, 26%, and 61%, respectively, for group C specimens. Forty-four percent of the 124 specimens in group D were positive in the RSV-F IgA EIA. The RSV-F protein IgA EIA exhibited a high level of sensitivity and specificity for detecting previous RSV infections in the presence of maternal antibodies and can help in RSV clinical trials and epidemiologic studies in young children.

Integrating a Virtual Assistant by Using the RAG Method and VERTEX AI Framework at Algebra University

The development and testing of a virtual assistant (VA) designed to enhance information retrieval and support in an academic environment are presented in this paper, with the Retrieval-Augmented Generation (RAG) approach being utilized alongside Google’s VERTEX AI Palm-2 model. A novel integration of RAG with contextual learning is introduced in this study, specifically for applications in university contact centers, where accuracy and relevance are considered paramount. The effectiveness of the VA was evaluated through user testing, focusing on two primary hypotheses: first, that the VA can achieve accurate interpretation and response to queries with context-based information, and second, that the VA minimizes potential harm from erroneous responses. In total, 187 participants were involved in the testing, and a diverse set of inquiries was utilized, resulting in 561 query–response interactions that were analyzed. It was shown that contextual data significantly reduced hallucinations and increased response accuracy, thereby underscoring the value of the RAG method in applications requiring high levels of specificity. Furthermore, the study provides empirical insights into the impact of AI-generated hallucinations and response inconsistencies, particularly about structured or procedural data. A framework for mitigating these challenges in future implementations is also offered. The scalability and adaptability of the RAG method in specialized academic contexts are demonstrated in this work, with broader implications for integrating AI-driven VAs across educational and professional domains being highlighted.

Evidence of Zika virus circulation in human and livestock in Chad

Zika virus (ZIKV) is a major public health problem worldwide. After several reported outbreaks, the current extent of infections caused by this orthoflavivirus in the Sahel remains to be explored. We investigated the prevalence of neutralizing antibodies against ZIKV in the general population, in HIV-infected individuals and in livestock in Chad using a seroneutralization assay that ensures high specificity level. In this retrospective serological serosurveillance investigation, we estimated the neutralizing seroprevalence to be approximately 26 % (18/69) in healthy Chadian participants and 17 % (16/94) in HIV-infected individuals, with no statistical difference between these two subgroups or genders. In addition, we found an overall ZIKV prevalence of 14 % (8/59) in small ruminants (sheep and goats) living in the Lake Chad Basin area, demonstrating virus circulation in animals. Our pilot study shows for the first-time evidence of ZIKV circulation in humans and in livestock in Chad in close interaction with humans, and highlights the main challenges associated with this virus in Sahelian areas.

Molecular Detection and Genotyping of Chlamydia psittaci in Birds in Buenos Aires City, Argentina.

Chlamydia psittaci is a bacterium that infects several species of birds and mammals. It is the causal agent of avian chlamydiosis and psittacosis in humans and it is globally distributed. Chlamydia psittaci is one of the main zoonotic pathogens transmitted by birds. In Argentina, there has been limited research on the prevalence and genetic variability of C. psittaci. The aim of this study was to detect and genotype C. psittaci using molecular techniques in birds living in Buenos Aires City, Argentina, during the period 2012-2015. A descriptive, observational, retrospective and cross-sectional study was carried out. A total of 983 bird samples submitted for diagnosis of avian chlamydiosis were analyzed. The frequency of C. psittaci was 12.54% and 7.89% in Psittaciformes and Columbiformes, respectively. A 348 bp region of the ompA gene was sequenced in positive samples. Molecular genotyping was performed through a Bayesian phylogenetic analysis. Of the 983 bird samples, 83 were positive for C. psittaci and 44 could be sequenced. The genotypes found were A, B, and E. Despite the high levels of host specificity, we found six psittacids with genotype B and one pigeon with genotype A, reflecting the affiliative interaction between Psittaciformes and Columbiformes. This study represents the first survey reporting the presence of C. psittaci in birds within the largest and most populous city in Argentina.

Evaluation of Immunochromatographic Test for Rapid Detection of Norovirus, Rotavirus, and Adenovirus in Stool Samples.

Viral enteric infections are illnesses caused by several types of viruses that primarily affect the gastrointestinal system. Globally, three major viruses associated with gastroenteritis, including norovirus (NoV), rotavirus A (RVA), and human adenovirus (HAdV), have been widely recognized. Accordingly, a rapid and sensitive diagnostic tool, such as immunochromatographic (IC) test, for diarrheal virus detection is required and helpful for rapid diagnosis. The IP-Triple I IC test kit for simultaneous triple virus detections of NoV, RVA, and HAdV was evaluated for its efficacy by using stool specimens that were known positive for these viruses by real-time RT-PCR or PCR, which was used as the gold standard method. The results revealed that the IP-Triple I IC test kit exhibited a very high level of specificity (100%) for NoV, RVA, and HAdV detections, while the sensitivity was slightly different for these three viruses. The sensitivity of detection for RVA was 86.7%, whereas those for NoV and HAdV were 70.6% and 76.2%, respectively. This IP-Triple I IC kit could detect common antigens of a wide range of NoV, RVA, and HAdV genotypes (NoV GII.2, GII.4, GII.6, GII.7, GII.10, GII.17, RVA G1P[8], G2P[4], G3P[8], G8P[8], G9P[8], HAdV-C1, -C2, -C5, -A12, -F40, and -F41). Our results revealed that the IP-Triple I IC test kit is highly effective for simultaneous, direct detection of common antigens of several genotypes of NoV, RVA, and HAdV in stool specimens and useful for screening and rapid diagnosis of diarrheal viruses during the seasonal outbreak.

Advancements in Hyperspectral Imaging and Computer-Aided Diagnostic Methods for the Enhanced Detection and Diagnosis of Head and Neck Cancer.

Background/Objectives: Head and neck cancer (HNC), predominantly squamous cell carcinoma (SCC), presents a significant global health burden. Conventional diagnostic approaches often face challenges in terms of achieving early detection and accurate diagnosis. This review examines recent advancements in hyperspectral imaging (HSI), integrated with computer-aided diagnostic (CAD) techniques, to enhance HNC detection and diagnosis. Methods: A systematic review of seven rigorously selected studies was performed. We focused on CAD algorithms, such as convolutional neural networks (CNNs), support vector machines (SVMs), and linear discriminant analysis (LDA). These are applicable to the hyperspectral imaging of HNC tissues. Results: The meta-analysis findings indicate that LDA surpasses other algorithms, achieving an accuracy of 92%, sensitivity of 91%, and specificity of 93%. CNNs exhibit moderate performance, with an accuracy of 82%, sensitivity of 77%, and specificity of 86%. SVMs demonstrate the lowest performance, with an accuracy of 76% and sensitivity of 48%, but maintain a high specificity level at 89%. Additionally, in vivo studies demonstrate superior performance when compared to ex vivo studies, reporting higher accuracy (81%), sensitivity (83%), and specificity (79%). Conclusion: Despite these promising findings, challenges persist, such as HSI's sensitivity to external conditions, the need for high-resolution and high-speed imaging, and the lack of comprehensive spectral databases. Future research should emphasize dimensionality reduction techniques, the integration of multiple machine learning models, and the development of extensive spectral libraries to enhance HSI's clinical utility in HNC diagnostics. This review underscores the transformative potential of HSI and CAD techniques in revolutionizing HNC diagnostics, facilitating more accurate and earlier detection, and improving patient outcomes.

Evaluation of the Seegene Allplex™ RV master assay for one-step simultaneous detection of eight respiratory viruses in nasopharyngeal specimens

BackgroundThe Seegene Allplex™ RV Master (RVM) assay is a one-step multiplex real-time reverse transcription polymerase chain reaction (RT-PCR) system for detecting eight viral respiratory pathogens from nasopharyngeal swab, aspirate, and bronchoalveolar lavage specimens. The eight RVM targets are: severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Influenza A (Flu A), Influenza B (Flu B), Human respiratory syncytial virus (RSV), adenovirus (AdV), rhinovirus (HRV), parainfluenza virus (PIV), and metapneumovirus (MPV). The assay is based on Seegene’s multiple detection temperature (MuDT) technology and provides cycle threshold (Ct) values for each of its viral targets upon PCR completion. ObjectiveWe aimed to evaluate the diagnostic performance of the RVM assay by calculating sensitivity, specificity, accuracy, Positive Predictive Value (PPV), Negative Predictive Value (NPV), Positive Percent Agreement (PPA), Negative Percent Agreement (NPA), and Overall Percent Agreement (OPA) compared to definite diagnosis and analogous reference assays. Study designDiagnostic sensitivity, specificity, accuracy, PPV, and NPV were calculated by comparing the results of the RVM assay to that of definite diagnosis assays; while PPA, NPA, and OPA were calculated by comparing results of the RVM assay to that of analogous reference products. Definite diagnosis and reference methods comprised whole genome sequencing and PCR genotyping, the Allplex™ SARS-CoV-2/FluA/FluB/RSV and Respiratory Panels 1, 2, and 3 assays (Seegene), and the Xpert® Xpress SARS-CoV-2/FluA/FluB/RSV Plus assay (Cepheid). Reproducibility of the RVM assay using fully-automated and semi-automated nucleic acid (NA) extraction workflows and as performed by independent operators was also assessed. In total, 249 positive respiratory specimens and at least 50 negative specimens for each target tested were used for this evaluation study. ResultsSensitivity, specificity, accuracy, PPV, NPV, PPA, NPA, and OPA ranged from 95.7 % to 100 % for detecting all eight targets tested on the RVM assay. Reproducibility PPA, NPA, and OPA between automated and semi-automated NA extraction workflows were all >97.9 %, while the reproducibility PPA, NPA and OPA between independent operators were all 100 %. ConclusionThese results demonstrate a high level of sensitivity, specificity, accuracy and diagnostic predictive value of the RVM assay and high agreement with comparable reference assays in identifying all eight of its targets. Taken together, our study underscores the diagnostic utility of the RVM assay in detecting eight viral respiratory pathogens.

Verified Lock-Free Session Channels with Linking

Type systems and program logics based on session types provide powerful high-level reasoning principles for message-passing concurrency. Modern versions employ bidirectional session channels that (1) are asynchronous so that send operations do not block, (2) have buffers in both directions so that both parties can send messages in parallel, and (3) feature a link operation (also called forward) to concisely write programs in process style. These features complicate a low-level lock-free implementation of channels and therefore increase the gap between the meta theory of prior work—which is verified w.r.t. a high-level semantics of channels (e.g., π-calculus)—and the code that runs on an actual computer. We address this problem by verifying a low-level lock-free implementation of session channels w.r.t. a high-level specification based on session types. We carry out our verification in a layered manner by employing the Iris framework for concurrent separation logic. We start with an abstract specification of (unidirectional) queues—of which we provide a linked-list and array-segment based implementation—and gradually build up to session channels with all of the aforementioned features. To make a layered verification possible we develop two logical abstractions—queues with ghost linking and pairing invariants—to reason about the atomicity and changing endpoints due to linking, respectively. All our results are mechanized in the Coq proof assistant.

TRNA-derived fragment tRF-30 propels diabetes-induced retinal microvascular complications by regulating STAT3 signaling.

Transfer RNA-derived fragments (tRFs) represent a novel class of non-coding RNA transcripts that possess specific biological functions. However, the involvement of tRFs in retinal microvascular diseases remains poorly understood. In this study, we aimed to reveal whether modulation of tRF-30 expression could attenuate pathological retinal neovascular diseases. Our findings demonstrate a significant upregulation of tRF-30 expression levels in both in vivo models of diabetic retinopathy (DR) and in vitro endothelial sprouting models. Conversely, inhibition of tRF-30 expression suppressed the formation of abnormal neovascularization in the retina in vivo, while reducing the proliferation and migration activity of retinal vascular endothelial cells in vitro. We also found that tRF-30 modulates retinal neovascularization through the tRF-30/TRIB3/signal transducer and activated transcription 3 signaling pathway. Furthermore, we validated a significant upregulation of tRF-30 expression levels in the vitreous humor of DR patients, with high levels of both validity and specificity in diagnostic testing. Collectively, our findings highlight a pro-angiogenic role for tRF-30 in DR. Intervening in the tRF-30 signaling pathway may represent a promising prevention and treatment strategy for retinal angiogenesis.

Artificial Flowers in the Credit Records of an Eighteenth-Century French Fashion Merchant

Abstract In recent decades, historians have acknowledged the role that women played in shaping and disseminating scientific knowledge during the Enlightenment. Current scholarship also suggests that fashion was a means through which haptic, economic, and practical knowledge was shared among women. This article focuses on one particular fashion accessory – the artificial flower – to explore its contribution to our understanding of women’s knowledge of botany in eighteenth-century France. An analysis of the receipts preserved in the credit records of France’s most famous fashion merchant, Marie-Jeanne (Rose) Bertin (1747–1813), demonstrates high levels of specificity in the flowers that women chose to adorn their outfits. Seventy-five different types of flowers are mentioned using their vernacular names, suggesting that knowledge about a wide variety of flowers was exchanged between fashion merchants and their clients during conversations about clothing. This article therefore casts the fashion merchant’s shop as a site of botanical knowledge generation and exchange.