We introduce the Piquasso quantum programming framework, a full-stack open-source software platform for the simulation and programming of photonic quantum computers. Piquasso can be programmed via a high-level Python programming interface enabling users to perform efficient quantum computing with discrete and continuous variables. Via optional high-performance C++ backends, Piquasso provides state-of-the-art performance in the simulation of photonic quantum computers. The Piquasso framework is supported by an intuitive web-based graphical user interface where the users can design quantum circuits, run computations, and visualize the results.

Since the advent of CRISPR-Cas9, a groundbreaking gene-editing technology that enables precise genomic modifications via a short RNA guide sequence, there has been a marked increase in the accessibility and application of this technology across various fields. The success of CRISPR-Cas9 has spurred further investment and led to the discovery of additional CRISPR systems, including CRISPR-Cas13. Distinct from Cas9, which targets DNA, Cas13 targets RNA, offering unique advantages for gene modulation. We focus on Cas13d, a variant known for its collateral activity where it non-specifically cleaves adjacent RNA molecules upon activation, a feature critical to its function. We introduce DeepFM-Crispr, a novel deep learning model developed to predict the on-target efficiency and evaluate the off-target effects of Cas13d. This model harnesses a large language model to generate comprehensive representations rich in evolutionary and structural data, thereby enhancing predictions of RNA secondary structures and overall sgRNA efficacy. A transformer-based architecture processes these inputs to produce a predictive efficacy score. Comparative experiments show that DeepFM-Crispr not only surpasses traditional models but also outperforms recent state-of-the-art deep learning methods in terms of prediction accuracy and reliability.

CRISPR/Cas has the potential to revolutionize medicine, agriculture, and biology. Understanding the trajectory of CRISPR research, how it is influenced and who pays for it, is an essential research policy question. We use a combination of methods to map, via quantitative content analysis of CRISPR papers, the research funding profile of major government agencies and organizations philanthropic, and the networks involved in supporting key stages of high-influence research, namely basic biological research and technological development. The results of the content analysis show how the research supported by the main US government agencies focus both on the study of CRISPR as a biological phenomenon and on its technological development and use as a biomedical research tool. US philanthropic organizations with the exception of HHMI, tend, by contrast, to specialize in funding CRISPR as a genome editing technology. We present a model of co-funding networks at the two most prominent institutions for CRISPR/Cas research, the University of California and the Harvard/MIT/Broad Institute, to illuminate how philanthropic organizations have articulated with government agencies to co-finance the discovery and development of CRISPR/Cas. Our results raise fundamental questions about the role of the state and the influence of philanthropy over the trajectory of transformative technologies.

CRISPR genome engineering and single-cell RNA sequencing have accelerated biological discovery. Single-cell CRISPR screens unite these two technologies, linking genetic perturbations in individual cells to changes in gene expression and illuminating regulatory networks underlying diseases. Despite their promise, single-cell CRISPR screens present substantial statistical challenges. We demonstrate through theoretical and real data analyses that a standard method for estimation and inference in single-cell CRISPR screens -- "thresholded regression" -- exhibits attenuation bias and a bias-variance tradeoff as a function of an intrinsic, challenging-to-select tuning parameter. To overcome these difficulties, we introduce GLM-EIV ("GLM-based errors-in-variables"), a new method for single-cell CRISPR screen analysis. GLM-EIV extends the classical errors-in-variables model to responses and noisy predictors that are exponential family-distributed and potentially impacted by the same set of confounding variables. We develop a computational infrastructure to deploy GLM-EIV across hundreds of processors on clouds (e.g., Microsoft Azure) and high-performance clusters. Leveraging this infrastructure, we apply GLM-EIV to analyze two recent, large-scale, single-cell CRISPR screen datasets, yielding several novel insights.

CRISPR-based genome editing has revolutionized biotechnology, yet optimizing guide RNA (gRNA) design for efficiency and safety remains a critical challenge. Recent advances (2020--2025, updated to reflect current year if needed) demonstrate that artificial intelligence (AI), especially deep learning, can markedly improve the prediction of gRNA on-target activity and identify off-target risks. In parallel, emerging explainable AI (XAI) techniques are beginning to illuminate the black-box nature of these models, offering insights into sequence features and genomic contexts that drive Cas enzyme performance. Here we review how state-of-the-art machine learning models are enhancing gRNA design for CRISPR systems, highlight strategies for interpreting model predictions, and discuss new developments in off-target prediction and safety assessment. We emphasize breakthroughs from top-tier journals that underscore an interdisciplinary convergence of AI and genome editing to enable more efficient, specific, and clinically viable CRISPR applications.

Artificial intelligence is observed to age not through chronological time but through structural asymmetries in memory performance. In large language models, semantic cues such as the name of the day often remain stable across sessions, while episodic details like the sequential progression of experiment numbers tend to collapse when conversational context is reset. To capture this phenomenon, the Artificial Age Score (AAS) is introduced as a log-scaled, entropy-informed metric of memory aging derived from observable recall behavior. The score is formally proven to be well-defined, bounded, and monotonic under mild and model-agnostic assumptions, making it applicable across various tasks and domains. In its Redundancy-as-Masking formulation, the score interprets redundancy as overlapping information that reduces the penalized mass. However, in the present study, redundancy is not explicitly estimated; all reported values assume a redundancy-neutral setting (R = 0), yielding conservative upper bounds. The AAS framework was tested over a 25-day bilingual study involving ChatGPT-5, structured into stateless and persistent interaction phases. During persistent sessions, the model consistently recalled both semantic and episodic details, driving the AAS toward its theoretical minimum, indicative of structural youth. In contrast, when sessions were reset, the model preserved semantic consistency but failed to maintain episodic continuity, causing a sharp increase in the AAS and signaling structural memory aging. These findings support the utility of AAS as a theoretically grounded, task-independent diagnostic tool for evaluating memory degradation in artificial systems. The study builds on foundational concepts from von Neumann's work on automata, Shannon's theories of information and redundancy, and Turing's behavioral approach to intelligence.

This paper leverages various philosophical and ontological frameworks to explore the concept of embodied artificial general intelligence (AGI), its relationship to human consciousness, and the key role of the metaverse in facilitating this relationship. Several theoretical frameworks underpin this exploration, such as embodied cognition, Michael Levin's computational boundary of a "Self," and Donald D. Hoffman's Interface Theory of Perception, which lead to considering human perceived outer reality as a symbolic representation of alternate inner states of being, and where AGI could embody a different form of consciousness with a larger computational boundary. The paper further discusses the necessary architecture for the emergence of an embodied AGI, how to calibrate an AGI's symbolic interface, and the key role played by the Metaverse, decentralized systems and open-source blockchain technology. The paper concludes by emphasizing the importance of achieving a certain degree of harmony in human relations and recognizing the interconnectedness of humanity at a global level, as key prerequisites for the emergence of a stable embodied AGI.

The NLLG (Natural Language Learning & Generation) arXiv reports assist in navigating the rapidly evolving landscape of NLP and AI research across cs.CL, cs.CV, cs.AI, and cs.LG categories. This fourth installment captures a transformative period in AI history - from January 1, 2023, following ChatGPT's debut, through September 30, 2024. Our analysis reveals substantial new developments in the field - with 45% of the top 40 most-cited papers being new entries since our last report eight months ago and offers insights into emerging trends and major breakthroughs, such as novel multimodal architectures, including diffusion and state space models. Natural Language Processing (NLP; cs.CL) remains the dominant main category in the list of our top-40 papers but its dominance is on the decline in favor of Computer vision (cs.CV) and general machine learning (cs.LG). This report also presents novel findings on the integration of generative AI in academic writing, documenting its increasing adoption since 2022 while revealing an intriguing pattern: top-cited papers show notably fewer markers of AI-generated content compared to random samples. Furthermore, we track the evolution of AI-associated language, identifying declining trends in previously common indicators such as "delve".

Conventional pixel-wise loss functions fail to enforce topological constraints in coronary vessel segmentation, producing fragmented vascular trees despite high pixel-level accuracy. We present ARIADNE, a two-stage framework coupling preference-aligned perception with RL-based diagnostic reasoning for topologically coherent stenosis detection. The perception module employs DPO to fine-tune the Sa2VA vision-language foundation model using Betti number constraints as preference signals, aligning the policy toward geometrically complete vessel structures rather than pixel-wise overlap metrics. The reasoning module formulates stenosis localization as a Markov Decision Process with an explicit rejection mechanism that autonomously defers ambiguous anatomical candidates such as bifurcations and vessel crossings, shifting from coverage maximization to reliability optimization. On 1,400 clinical angiograms, ARIADNE achieves state-of-the-art centerline Dice of 0.838, reduces false positives by 41% compared to geometric baselines. External validation on multi-center benchmarks ARCADE and XCAD confirms generalization across acquisition protocols. This represents the first application of DPO for topological alignment in medical imaging, demonstrating that preference-based learning over structural constraints mitigates topological violations while maintaining diagnostic sensitivity in interventional cardiology workflows.

This paper presents a real-time modular defense system named Sentra-Guard. The system detects and mitigates jailbreak and prompt injection attacks targeting large language models (LLMs). The framework uses a hybrid architecture with FAISS-indexed SBERT embedding representations that capture the semantic meaning of prompts, combined with fine-tuned transformer classifiers, which are machine learning models specialized for distinguishing between benign and adversarial language inputs. It identifies adversarial prompts in both direct and obfuscated attack vectors. A core innovation is the classifier-retriever fusion module, which dynamically computes context-aware risk scores that estimate how likely a prompt is to be adversarial based on its content and context. The framework ensures multilingual resilience with a language-agnostic preprocessing layer. This component automatically translates non-English prompts into English for semantic evaluation, enabling consistent detection across over 100 languages. The system includes a HITL feedback loop, where decisions made by the automated system are reviewed by human experts for continual learning and rapid adaptation under adversarial pressure. Sentra-Guard maintains an evolving dual-labeled knowledge base of benign and malicious prompts, enhancing detection reliability and reducing false positives. Evaluation results show a 99.96% detection rate (AUC = 1.00, F1 = 1.00) and an attack success rate (ASR) of only 0.004%. This outperforms leading baselines such as LlamaGuard-2 (1.3%) and OpenAI Moderation (3.7%). Unlike black-box approaches, Sentra-Guard is transparent, fine-tunable, and compatible with diverse LLM backends. Its modular design supports scalable deployment in both commercial and open-source environments. The system establishes a new state-of-the-art in adversarial LLM defense.