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Biological theory usually treats time as an external chronological variable against which growth, aging, and ecological change are parametrized. Yet living systems also generate an internal measure of duration through physiological cycling and irreversible entropy production, and the regularities of allometric lifespan scaling, biological clocks, life-history evolution, ecological synchronization, and disease are ordinarily studied in isolation rather than within a single thermodynamic internal-time framework. The Principle of Biological Time Equivalence (PBTE) proposes such a framework.
Inductive Logic Programming (ILP) originated within the Logic Programming community in the Nineties as a framework for combining symbolic learning with declarative knowledge representation. Nowadays, mature ILP frameworks exist and they are capable of learning complex, non-monotonic hypotheses, thus broadening both the modeling capabilities and the scope of real-world applications of ILP. This work is primarily based on the FastLAS2 framework and aims to generate simple, interpretable hypotheses to help clarify the weather bulletins issued by OSMER FVG, the Regional Meteorological Observatory of the Italian region of Friuli Venezia-Giulia. In this paper we present a pipeline that, starting from simulated meteorological raw data and from OSMERs' bulletins (used as ground truth), extracts data as ASP facts and generates ILP examples. From such examples an explanatory hypothesis is then inferred via FastLAS2. Such a hypothesis (translated into natural language) explains the weather forecast issued by human experts, and in particular the rationale behind experts' choices of specific symbols in the bulletin pictogram (the symbol-annotated meteorological map of the forecast). The propose
Observable performance is commonly used to characterize biological systems, yet aggregated outputs may remain insufficient for uniquely resolving observational conditions, and richer multivariate representations may retain substantial ambiguity. This article proposes a representational bootstrap framework for adaptive biological systems. Bootstrap is used in a methodological and epistemological sense, not as statistical resampling. New analytical levels emerge when the active representation becomes insufficient for the question under investigation. The framework comprises five successive levels: observable performance, conceptual dynamic organization, exploratory multivariate representation, observed longitudinal centroid displacement, and internal approximation of observed displacement. Three previously reported gait-occlusion studies are used as a methodological case sequence rather than as new experimental evidence. The revised first study showed persistent static representational non-identifiability: neither the scalar score nor the exploratory embedding uniquely resolved the occlusal probes. The second study shifted the question toward M1-M2 centroid displacement in a common P
There are innumerable 'biological complexity measure's. While some patterns emerge from these attempts to represent biological complexity, a single measure to encompass the seemingly countless features of biological systems, still eludes the students of Biology. It is the pursuit of this paper to discuss the feasibility of finding one complete and objective measure for biological complexity. A theoretical construct (the 'Thread-Mesh model') is proposed here to describe biological reality. It segments the entire biological space-time in a series of different biological organizations before modeling the property space of each of these organizations with computational and topological constructs. Acknowledging emergence as a key biological property, it has been proved here that the quest for an objective and all-encompassing biological complexity measure would necessarily end up in failure. Since any study of biological complexity is rooted in the knowledge of biological reality, an expression for possible limit of human knowledge about ontological biological reality, in the form of an uncertainty principle, is proposed here. Two theorems are proposed to model the fundamental limitatio
This paper surveys foundation models for AI-enabled biological design, focusing on recent developments in applying large-scale, self-supervised models to tasks such as protein engineering, small molecule design, and genomic sequence design. Though this domain is evolving rapidly, this survey presents and discusses a taxonomy of current models and methods. The focus is on challenges and solutions in adapting these models for biological applications, including biological sequence modeling architectures, controllability in generation, and multi-modal integration. The survey concludes with a discussion of open problems and future directions, offering concrete next-steps to improve the quality of biological sequence generation.
A collection of citation data, the HistComp, is available from the Internet as a database of examples of real life citation networks. The purposes of this approach is the analysis of these citation networks on learned literature by presenting its typical steps and results. We have selected the bibliographic insights into the "The Biological Bulletin", the journal published since 1897 by the Woods Hole Marine Biological Laboratory. Since the bibliographic networks tend to be very scattered, their visualization requires of criteria of convergence. To simplify, the main features in such a structure should include the survey for authoritative sources in the hyperlinked environment and the identification of thematic areas. By avoiding excessive loose connections and too dense clustered layouts to be useful, a smooth presentation is obtained by graphically depicting the citation patterns. HistComp computes 8884 articles published by 'The Biological Bulletin' between 1945-2003. A two-dimensional positioning of these papers that represent the extent of their bibliographic coupling and co-citation is offered as a histograph. The criteria to construct it is the adequateness of the visualizat
Primates exhibit a robust deviation from canonical allometric scaling: at fixed body mass, their lifespans exceed those of non-primate mammals by factors of two to three. A rhesus macaque (8 kg) lives 25-40 years, whereas a cat of similar mass rarely exceeds 18 years. This statistically significant clade-level excess cannot be explained by standard metabolic or ecological models. We provide a thermodynamic explanation within the Principle of Biological Time Equivalence (PBTE), where lifespan is determined by a finite cycle budget governed by entropy production. We show that primates reduce entropy production per physiological cycle through increased neural energy allocation. The neural power fraction acts as a control parameter, extending the effective lifetime cycle count. Three mechanisms, predictive regulation, enhanced repair, and behavioral buffering, jointly suppress dissipation. This yields a quantitative neuro-metabolic multiplier that explains primate longevity and provides testable predictions linking brain energetics, entropy production, and lifespan.
Pharmaceutical research and development has accumulated vast and heterogeneous archives of data. Much of this knowledge stems from discontinued programs, and reusing these archives is invaluable for reverse translation. However, in practice, such reuse is often infeasible. In this work, we introduce DiscoVerse, a multi-agent co-scientist designed to support pharmaceutical research and development at Roche. Designed as a human-in-the-loop assistant, DiscoVerse enables domain-specific queries by delivering evidence-based answers: it retrieves relevant data, links across documents, summarises key findings and preserves institutional memory. We assess DiscoVerse through expert evaluation of source-linked outputs. Our evaluation spans a selected subset of 180 molecules from Roche's research and development repositories, encompassing over 0.87 billion BPE tokens and more than four decades of research. To our knowledge, this represents the first agentic framework to be systematically assessed on real pharmaceutical data for reverse translation, enabled by authorized access to confidential archives covering the full lifecycle of drug development. Our contributions include: role-specialized
There are significant differences in innovation performance between countries. Additionally, the pharmaceutical sector is stronger in some countries than in others. This suggests that the development of the pharmaceutical industry can influence a country's innovation performance. Using the Global Innovation Index and selected performance measures of the pharmaceutical sector, this study examines how the pharmaceutical sector influences the innovation performance of countries from the European context. The dataset of 27 European countries was analysed using simple, and multiple linear regressions and Pearson correlation. Our findings show that only three indicators of the pharmaceutical industry, more precisely pharmaceutical Research and Development, pharmaceutical exports, and pharmaceutical employment explain the innovation performance of a country largely. Pharmaceutical Research and Development and exports have a significant positive impact on a country's innovation performance, whereas employment in the pharmaceutical industry has a slightly negative impact. Additionally, global innovation performance has been found to positively influence life expectancy. We further outline t
Many drugs have been withdrawn from the market worldwide, at a cost of billions of dollars, because of patient fatalities due to them unexpectedly disturbing heart rhythm. Even drugs for ailments as mild as hay fever have been withdrawn due to an unacceptable increase in risk of these heart rhythm disturbances. Consequently, the whole pharmaceutical industry expends a huge effort in checking all new drugs for any unwanted side effects on the heart. The predominant root cause has been identified as drug molecules blocking ionic current flows in the heart. Block of individual types of ionic currents can now be measured experimentally at an early stage of drug development, and this is the standard screening approach for a number of ion currents in many large pharmaceutical companies. However, clinical risk is a complex function of the degree of block of many different types of cardiac ion currents, and this is difficult to understand by looking at results of these screens independently. By using ordinary differential equation models for the electrical activity of heart cells (electrophysiology models) we can integrate information from different types of currents, to predict the effect
This document offers a critical overview of the emerging trends and significant advancements in artificial intelligence (AI) within the pharmaceutical industry. Detailing its application across key operational areas, including research and development, animal testing, clinical trials, hospital clinical stages, production, regulatory affairs, quality control and other supporting areas, the paper categorically examines AI's role in each sector. Special emphasis is placed on cutting-edge AI technologies like machine learning algorithms and their contributions to various aspects of pharmaceutical operations. Through this comprehensive analysis, the paper highlights the transformative potential of AI in reshaping the pharmaceutical industry's future.
Are biological self-organising systems more ``intelligent'' than artificial intelligence (AI)? If so, why? I address this question using a mathematical framework that defines intelligence in terms of adaptability. Systems are modelled as stacks of abstraction layers (\emph{Stack Theory}) and compared by how effectively they delegate agentic control down their stacks. I illustrate this using computational, biological, military, governmental, and economic systems. Contemporary AI typically relies on static, human-engineered stacks whose lower layers are fixed during deployment. Put provocatively, such systems resemble inflexible bureaucracies that adapt only top-down. Biological systems are more intelligent because they delegate adaptation. Formally, I prove a theorem (\emph{The Law of the Stack}) showing that adaptability at higher layers is bottlenecked by adaptability at lower layers. I further show that, under standard viability assumptions, maximising adaptability is equivalent to minimising variational free energy, implying that delegation is necessary for free-energy minimisation. Generalising bioelectric accounts of cancer as isolation from collective informational structures
The digital transformation of pharmaceutical industry is a challenging task due to the high complexity of involved elements and the strict regulatory compliance. Maintenance activities in the pharmaceutical industry play an essential role in ensuring product quality and integral functioning of equipment and premises. This paper first identifies the key challenges of digitalization in pharmaceutical industry and creates the corresponding problem space for key involved elements. A literature review is conducted to investigate the mainstream maintenance strategies, digitalization models, tools and official guidance from authorities in pharmaceutical industry. Based on the review result, a semantic-driven digitalization framework is proposed aiming to improve the digital continuity and cohesion of digital resources and technologies for maintenance activities in the pharmaceutical industry. A case study is conducted to verify the feasibility of the proposed framework based on the water sampling activities in Merck Serono facility in Switzerland. A tool-chain is presented to enable the functional modules of the framework. Some of the key functional modules within the framework are implem
We plan to simulate a private and unlinkable exchange of messages by using a Public bulletin board and Mix networks in Opportunistic networks. This Opportunistic network uses a secure and privacy-friendly asynchronous unidirectional message transmission protocol. By using this protocol, we create a Public bulletin board in a network that makes individuals send or receive events unlinkable to one another . With the design of a Public bulletin board in an Opportunistic network, the clients can use the benefits of this Public bulletin board in a safe environment. When this Opportunistic network uses the protocol, it can guarantee an unlinkable communication based on the Mix networks. The protocol can work with the Public bulletin board exclusively with acceptable performance. Also, this simulation can be used for hiding metadata in the bidirectional message exchange in some messengers such as WhatsApp. As we know, one of the main goals of a messenger like WhatsApp is to protect the social graph. By using this protocol, a messenger can protect social graph and a central Public bulletin board.
Current pharmaceutical formulation development still strongly relies on the traditional trial-and-error approach by individual experiences of pharmaceutical scientists, which is laborious, time-consuming and costly. Recently, deep learning has been widely applied in many challenging domains because of its important capability of automatic feature extraction. The aim of this research is to use deep learning to predict pharmaceutical formulations. In this paper, two different types of dosage forms were chosen as model systems. Evaluation criteria suitable for pharmaceutics were applied to assessing the performance of the models. Moreover, an automatic dataset selection algorithm was developed for selecting the representative data as validation and test datasets. Six machine learning methods were compared with deep learning. The result shows the accuracies of both two deep neural networks were above 80% and higher than other machine learning models, which showed good prediction in pharmaceutical formulations. In summary, deep learning with the automatic data splitting algorithm and the evaluation criteria suitable for pharmaceutical formulation data was firstly developed for the predi
Nowadays people realize that it is difficult to find information simply and quickly on the bulletin boards. In order to solve this problem, people propose the concept of bulletin board search engine. This paper describes the priscrawler system, a subsystem of the bulletin board search engine, which can automatically crawl and add the relevance to the classified attachments of the bulletin board. Priscrawler utilizes Attachrank algorithm to generate the relevance between webpages and attachments and then turns bulletin board into clear classified and associated databases, making the search for attachments greatly simplified. Moreover, it can effectively reduce the complexity of pretreatment subsystem and retrieval subsystem and improve the search precision. We provide experimental results to demonstrate the efficacy of the priscrawler.
We present the motivation, experience and learnings from a data challenge conducted at a large pharmaceutical corporation on the topic of subgroup identification. The data challenge aimed at exploring approaches to subgroup identification for future clinical trials. To mimic a realistic setting, participants had access to 4 Phase III clinical trials to derive a subgroup and predict its treatment effect on a future study not accessible to challenge participants. 30 teams registered for the challenge with around 100 participants, primarily from Biostatistics organisation. We outline the motivation for running the challenge, the challenge rules and logistics. Finally, we present the results of the challenge, the participant feedback as well as the learnings, and how these learnings can be translated into statistical practice.
Biological systems possess negative entropy. In them, one form of order produces another, more organized form of order. We propose a formal scheme to calculate robustness of an entire biological system by quantifying the negative entropy present in it. Our Methodology is based upon a computational implementation of two-person non-cooperative finite zero-sum game between positive (physico-chemical) and negative (biological) entropy, present in the system(TCA cycle, for this work). Biochemical analogue of Nash equilibrium, proposed here, could measure the robustness in TCA cycle in exact numeric terms, whereas the mixed strategy game between these entropies could quantitate the progression of stages of biological adaptation. Synchronization profile amongst macromolecular concentrations (even under environmental perturbations) is found to account for negative entropy and biological robustness. Emergence of synchronization profile was investigated with dynamically varying metabolite concentrations. Obtained results were verified with that from the deterministic simulation methods. Categorical plans to apply this algorithm in Cancer studies and anti-viral therapies are proposed alongsid
Biological systems, from a cell to the human brain, are inherently complex. A powerful representation of such systems, described by an intricate web of relationships across multiple scales, is provided by complex networks. Recently, several studies are highlighting how simple networks -- obtained by aggregating or neglecting temporal or categorical description of biological data -- are not able to account for the richness of information characterizing biological systems. More complex models, namely multilayer networks, are needed to account for interdependencies, often varying across time, of biological interacting units within a cell, a tissue or parts of an organism.
Provided that there is no theoretical frame for complex engineered systems (CES) as yet, this paper claims that bio-inspired engineering can help provide such a frame. Within CES bio-inspired systems play a key role. The disclosure from bio-inspired systems and biological computation has not been sufficiently worked out, however. Biological computation is to be taken as the processing of information by living systems that is carried out in polynomial time, i.e., efficiently; such processing however is grasped by current science and research as an intractable problem (for instance, the protein folding problem). A remark is needed here: P versus NP problems should be well defined and delimited but biological computation problems are not. The shift from conventional engineering to bio-inspired engineering needs bring the subject (or problem) of computability to a new level. Within the frame of computation, so far, the prevailing paradigm is still the Turing-Church thesis. In other words, conventional engineering is still ruled by the Church-Turing thesis (CTt). However, CES is ruled by CTt, too. Contrarily to the above, we shall argue here that biological computation demands a more ca