Human Agents Research Articles

Ixodes scapularis Is the Most Susceptible of the Three Canonical Human-Biting Tick Species of North America to Repellent and Acaricidal Effects of the Natural Sesquiterpene, (+)-Nootkatone.

Ticks are vectors of many human and animal zoonotic disease-causing agents causing significant global health and economic strain. Repellents and acaricides are integral to the human capacity for personal protection from tick bites. Nootkatone, a naturally occurring sesquiterpene found in the Alaskan cedar tree, grapefruit, and other sources, has been documented to be a potent acaricide. Research has also noted repellent effects against some tick species. In this study, our aim was to investigate the effect of synthetic, high-purity (+)-nootkatone on adult Ixodes scapularis, Dermacentor variabilis, and Amblyomma americanum ticks in an in vitro, vertical filter paper bioassay. (+)-nootkatone showed compelling tick repellency, but median effective concentrations (EC50) significantly differed among species. Ixodes scapularis were repelled at very low concentrations (EC50 = 0.87 ± 0.05 µg/cm2). Higher concentrations were required to repel D. variabilis (EC50 = 252 ± 12 µg/cm2) and A. americanum (EC50 = 2313 ± 179 µg/cm2). Significant post-exposure mortality, assessed 24 h after repellency trials, was also observed in I. scapularis but was absent entirely in D. variabilis and A. americanum. These tests demonstrate that nootkatone has a promising dual-action personal protection capacity against adult I. scapularis ticks, warranting further investigation in more natural environments and in the presence of host cues.

Semantic Technologies to Model Battery Data and Knowledge

Data-intensive battery research is here to stay. With open data incentives on the rise and simpler software interfaces granting access to powerful machine learning algorithms, researchers are uncovering a wealth of insights from battery data. However, data without context are just unusable digital bits. Battery data must be appropriately described to render it interoperable and reusable for traditional and data-intensive research. This requires overcoming numerous challenges associated to data heterogeneity, inconsistency, standardization, and meaning. Semantic technologies address these challenges by providing a unified and flexible framework for integrating and reasoning about data from heterogeneous sources.In this contribution, we will introduce Semantic Technologies and how they enable both human and software agents to understand and reuse battery data. We will present the tools we are developing to i) encourage the adoption of a common standard vocabulary to describe the battery domain[1], ii) connect research resources (datasets, experts, reports, publications, projects) within an accessible platform[2], and iii) reduce the effort required to upgrade data with semantic context. Overall, these tools take concrete steps towards guaranteeing compliance with FAIR data principles. We will further outline plans for future development, including strategies for reaching out to the global battery landscape, facilitate the curation of battery data for data-driven research, and enable knowledge exploration via natural language models.[1] S. Clark et al., "Toward a Unified Description of Battery Data," Adv. Energy Mater., vol. 2102702, 2021.[2] https://github.com/BIG-MAP/Demo-BatteryDataSemanticSearch

Neuroprotective effect of 2-ethyl-6-methyl-3-hydroxypyridine succinate on the sciatic nerve and its segmental centers in experimental paclitaxel-induced peripheral neuropathy

Up to 60 % of patients suffer from the neurotoxicity of the chemotherapy drug Paclitaxel, namely paclitaxel-induced peripheral neuropathy (PIPN), during the treatment of breast cancer, ovarian cancer, and non-small cell lung cancer. Of these, up to 25 % of patients require modification of the paclitaxel treatment regimen, including dose reduction, delay, or discontinuation of therapy. Previous attempts to use neuroprotective agents in humans and in animal models have not shown sufficient efficacy in preventing or significantly reducing the manifestations of PIPN. The aim of our study was to study the effect of the neuroprotective agent 2-ethyl-6-methyl-3-hydroxypyridine succinate (HS) on the morpho-functional parameters of the sciatic nerve and its segmental centers in experimental PIPN. In the experiment, 56 white rats were used, which were injected intraperitoneally with Paclitaxel at a dose of 2 mg/kg of body weight 4 times after one day, after which the animals were divided into an experimental group – 24 animals that were injected with HS and a control group (24 animals, injection of water for injections). The method of studying mechanical allodynia was von Frey monofilaments, thermal hyperalgesia was studied by the hot plate test, and the electron microscopic examination was carried out according to generally accepted methods and studied with the help of a PEM-125 K electron microscope. The results of the hot plate test and the use of von Frey monofilaments showed that the use of HS reliably reduces manifestations of PIPN on the 7th, 14th and 28th days of the experiment. In rats treated with HS, destructive-dystrophic phenomena in the myelin nerve fibers of the sciatic nerve are less pronounced, and in individual fibers in the axon, phenomena of incomplete splitting of mitochondria with the formation of vacuoles filled with medium electron density contents are observed, and small young mitochondria are also visualized. During the first 28 days, we noted less pronounced destructive-dystrophic changes in the neurons of the spinal cord nodes, namely: chromatolysis of light and dark neurons and swelling of their cytoplasm, phenomena of neuronophagy in gliocytes, hypertrophy of certain areas of the myelin sheath. The results of the electron microscopic study are fully consistent with the data of neurophysiological studies and indicate the possibility of using HS as an effective neuroprotector in PIPN.

Toward a Nonhuman Narratology: Material Metaphors in Ann Pancake’s Strange as this Weather Has Been

This paper examines the convergence of affect theory and cognitive narratology. I investigate the methodological potential of a cognitive narratology informed by affect as found in the (autonomous) intensities and resonances that circulate about and between bodies (Gregory J. Seigworth and Melissa Gregg). By adopting Brian Massumi’s configuration of affect (as asymbolic, autonomous and asubjective), I aim to explore how this conception can account for nonhuman (narrative) agents and open up space for alternative forms of environmental situatedness in cognitive narratology. Expanding upon the “4E” cognitive model, I trace the enmeshment of human and non-human agents within the metaphorical pattern of Ann Pancake’s 2007 novel Strange as This Weather Has Been. I undertake an analysis of multiple extra- and inter-textual vectors to show how these metaphors underscore a view of cognition as participating in a field of affective intensities and becomings and highlight its emergence as entangled in a world of material interdependencies.

The Chinese View on Time – A Reflection on The Concept of Time in Dao/Yijing And Modern Science

This paper investigates the intricate relationship between consciousness, time, and free will action by human agents intermediated between the construct of Heaven and Earth. By conducting a comprehensive literature review across different disciplines, such as Chinese philosophy, and reflecting on time and related ideas in _Yijing_, the time perspective in the arrow of time in modern science, insights into the nature of time and its implications can be gained. While the second law of thermodynamics supports a one-directional time arrow, microscopic fluctuations complicate this understanding. In addition, cultural and historical factors have influenced our understanding of time, highlighting the need for interdisciplinary inquiry. The research challenges causality principles and introduces a Co-Occurrence Time Model, raising questions about the independence of time from an observer. The study emphasizes the importance of a comprehensive approach to understanding human experience and calls for further investigation into these concepts. The paper underscores the need to explore the multifaceted aspects of time, consciousness, and free will to broaden our understanding of the world and our place within the 天人地 _tian ren di _framework.

Idiotopes of antibodies against HIV-1 CD4-induced epitope shared with those against microorganisms.

Induction of antibodies (Abs) against the conformational CD4-induced (CD4i) epitope is frequent in HIV-1 infection. However, the mechanism of development of anti-CD4i Abs is unclear. We used anti-idiotypic (aID) monoclonal Abs (mAbs) of anti-CD4i mAbs to isolate anti-CD4i mAbs from infected subjects and track the causative antigens. One anti-aID mAb sorted from infected subjects by aID mAbs had the characteristics of anti-CD4i Abs, including IGHV1-69 usage and ability to bind to HIV-1 Env enhanced by sCD4. Critical amino acid sequences for the binding of six anti-aID mAbs, with shared idiotope to anti-CD4i mAbs, were analysed by phage display. The identified amino acid sequences showed similarity to proteins from human microbiota and infectious agents. Peptides synthesized from Caudoviricetes sp and Vibrio vulnificus based on the identified sequences were reactive to most anti-aID and some anti-CD4i mAbs. These results suggest that anti-CD4i Abs may evolve from B cells primed by microorganisms.

Situation identification in smart wearable computing systems based on machine learning and Context Space Theory

Wearable devices and smart sensors are increasingly adopted to monitor the behaviors of human and artificial agents. Many applications rely on the capability of such devices to recognize daily life activities performed by the monitored users in order to tailor their behaviors with respect to the occurring situations. Despite the constant evolution of smart sensing technologies and the numerous research in this field, an accurate recognition of in-the-wild situations still represents an open research challenge. This work proposes a novel approach for situation identification capable of recognizing the activities and the situations in which they occur in different environments and behavioral contexts, processing data acquired by wearable and environmental sensors.An architecture of a situation-aware wearable computing system is proposed, inspired by Endsley’s situation-awareness model, consisting of a two-step approach for situation identification. The approach first identifies the daily life activities via a learning-based technique. Simultaneously, the context in which the activities are performed is recognized using Context Space Theory. Finally, the fusion between the context state and the activities allows identifying the complex situations in which the user is acting. The knowledge regarding the situations forms the basis on which novel and smarter applications can be realized.The approach has been evaluated on the ExtraSensory public dataset and compared with state-of-the-art techniques, achieving an accuracy of 96% for the recognition of situations and with significantly low computational time, demonstrating the efficacy of the two-step situation identification approach.

Is this a violation? Learning and understanding norm violations in online communities

Using norms to guide and coordinate interactions has gained tremendous attention in the multi-agent community. However, new challenges arise as the interest moves towards dynamic socio-technical systems, where human and software agents interact, and interactions are required to adapt to human's changing needs. For instance, different agents (human or software) might not have the same understanding of what it means to violate a norm (e.g., what characterizes hate speech), or their understanding of a norm might change over time (e.g., what constitutes an acceptable response time). The challenge is to address these issues by learning the meaning of a norm violation from limited interaction data. For this, we use batch and incremental learning to train an ensemble of classifiers. Ensemble learning and data-sampling handle the imbalanced class distribution of the interaction stream. At the same time, the training approaches use different strategies to ensure that the ensemble models reflect the latest community view on the meaning of norm violation. Batch learning uses weight assignment, while incremental learning continuously updates the ensemble models as community members interact. Here, we extend our previous work by creating a different balance strategy for online learning and integrating interpretability to understand norm violations. Additionally, we evaluate the proposed approaches in the context of Wikipedia article edits, where interactions revolve around editing articles, and the norm in question is prohibiting vandalism. Lastly, we conduct ablation studies to compare the ensemble's performance against a single model approach and to examine the behavior of two data sampling techniques. Results indicate that the different machine learning frameworks can learn the meaning of a norm violation in a setting with data imbalance and concept drift, although with significant differences.

Exploring the Role of AR Cognitive Interface in Enhancing Human-Vehicle Collaborative Driving Safety: A Design Perspective

In autonomous driving vehicles, the heterogeneity between human and automation agents can cause conflicts in decision-making and behaviour due to the difference in perception of hazardous situations. Augmented Reality Human-Machine Interfaces (AR-HMI) provide an opportunity to support driving performance by enabling drivers to intuitively access shared perception and explanation of the automated vehicle. One possible approach to AR-HMI design is to simplify the information of driving tasks based on vehicle context understanding, although there is currently a lack of systematic understanding of how collaborative mechanisms or cognitive features contribute to AR-HMI information design. Therefore, this work develops an augmented reality cognitive interface design method for autonomous driving. It aims to identify novel collaborative interface information visualization and provide a common language and inspiration for the design space.

Production, expression, and function of dual-specific monoclonal antibodies in a single plant.

LSC CO17-1AK and anti-HER2 VHH-FcK can be produced in a single plant and exhibit anti-tumor activities comparable to those of their respective parent antibodies. Recombinant monoclonal antibodies (mAbs) which can be applied to treat various cancers, are primarily produced using mammalian, insect, and bacteria cell culture systems. Plant expression systems have also been developed to produce antibodies. Plant expression systems present several advantages, including a lack of human pathogenic agents, efficient production costs, and easy large-scale production. In this study, we generated a transgenic plant expressing anti-colorectal cancer large single chain (LSC) CO17-1AK and anti-human epidermal growth factor receptor 2 (HER2) VHH-FcK mAbs by cross-pollinating plants expressing LSC CO17-1AK and anti-HER2 VHH-FcK, respectively. F1 siblings expressing both LSC CO17-1AK and anti-HER2 VHH-FcK were screened using polymerase chain reaction and Western-blot analyses. The cell enzyme-linked immunosorbent assay (Cell ELISA) confirmed the binding of LSC CO17-1AK and anti-HER2 VHH-FcK to target proteins in the SW620 human colorectal cancer and the SKBR-3 human breast cancer cell lines, respectively. The wound healing assay confirmed the inhibitory activity of both antibodies against SW620 and SKBR-3 cell migration, respectively. In conclusion, both LSC CO17-1AK mAb and anti-HER2 VHH-FcK can be produced in a single plant, achieve binding activities to SW620 and SKBR-3 cancer cells, and inhibitory activity against SW620 and SKBR-3 cell migration similar to their parental antibodies, respectively.

The Role of Trust in Dependence Networks: A Case Study

In a world where the interconnection and interaction between human and artificial agents are continuously increasing, the dynamics of social bonds and dependence networks play a fundamental role. The core of our investigation revolves around the intricate interplay between dependence and trust within a hybrid society, populated by human and artificial agents. By means of a structural theory, this study offers valuable insights into the utilization of dependence networks and their impact on collaborative dynamics and resource management. Most notably, agents that leverage dependence, even at the cost of interacting with low-trustworthiness partners, achieve superior performance in resource-constrained environments. On the other hand, in contexts where the use of dependence is limited, the role of trust is emphasized. These findings underscore the significance of dependence networks and their practical implications in real-world contexts, offering useful practical implications in areas such as robotics, resource management, and collaboration among human and artificial agents.

ASSESSING THE EFFECTIVENESS OF INPAINTING TECHNIQUES FOR ENHANCING FEATURE EXTRACTION QUALITY IN REMOTE SENSING IMAGERY

Abstract. Remote Sensing (RS) images have been used in several applications of interest for society. Despite the precision and robustness derived from RS images, several aerial scenes exhibit imperfections and fall short of attaining ideal quality standards, as some of them present distortions such as noise, blur, and stripes. An alternative approach to deal with such distortions is by applying Inpainting techniques, however, under certain circumstances, this type of approach requires to be evaluated by quantitative metrics to assess the final quality of the reconstruction. Therefore, this paper focus on the issue of quantitatively evaluating inpainting results in the context of RS by analysing and comparing new evaluation metrics in contrast to the classical ones from the general literature of RS. More precisely, two inpainting techniques are applied for object removal and reconstruction of partially detected curvilinear cartographic features in RS images. Next, the obtained results are evaluated by taking six evaluation metrics to assess the agreement level between the metrics, as well as between qualitative evaluations conducted by human agents. Based on the evaluation of these metrics when applied to RS images, it can be concluded that the DISTS and VSI metrics are the most promising candidates for adaptation and application within the specific context of RS.

A metatranscriptomic evaluation of viruses in field-collected bed bugs.

Cimex lectularius, known as the common bed bug, is a widespread hematophagous human ectoparasite and urban pest that is not known to be a vector of any human infectious disease agents. However, few studies in the era of molecular biology have profiled the microorganisms harbored by field populations of bed bugs. The objective of this study was to examine the viruses present in a large sampling of common bed bugs and related bat bugs (Cimex pipistrelle). RNA sequencing was undertaken on an international sampling of > 500 field-collected bugs, and multiple workflows were used to assemble contigs and query these against reference nucleotide databases to identify viral genomes. Shuangao bed bug virus 2, an uncharacterized rhabdovirus previously discovered in Cimex hemipterus from China, was found in several bed bug pools from the USA and Europe, as well as in C. pipistrelle, suggesting that this virus is common among bed bug populations. In addition, Shuangao bed bug virus 1 was detected in a bed bug pool from China, and sequences matching Enterobacteria phage P7 were found in all bed bug pools, indicating the ubiquitous presence of phage-derived elements in the genome of the bed bug or its enterobacterial symbiont. However, viral diversity was low in bed bugs in our study, as no other viral genomes were detected with significant coverage. These results provide evidence against frequent virus infection in bed bugs. Nonetheless, our investigation had several important limitations, and additional studies should be conducted to better understand the prevalence and composition of viruses in bed bugs. Most notably, our study largely focused on insects from urban areas in industrialized nations, thus likely missing infrequent virus infections and those that could occur in rural or tropical environments or developing nations.

Conscience and the continuum of constitutionalism: John Calvin on civil government

Abstract This article examines John Calvin’s theology on its own terms with the aim of appreciating the normative basis and implications of his political theory. Although the claim that Calvin’s account of civil government falls within the category of political ‘theology’ is less controversial, the normative implications of his theological ontology for political actors are more commonly contested. Calvin seminally wrote ‘on Civil Government’ in Book IV, Chapter xx of the Institutes of the Christian Religion. In contrast, his accounts of conscience and natural law are far less systemized.1 This article contends that this reticence is not due to lack of importance but rather, due to its foundational nature. Indeed, the opening statement of the Institutes is indicative of the coherence of the Reformer’s thoughts wherein any emerging polity is composed of what this article refers to as the ‘spheres-of-influence’ scheme—a normative system originating inward from the vertical relationship every human agent has with the divine, and then extending horizontally outwards to bind the collective in a common system of values. Such an ontology is predicated on the concepts of conscience and the divine image, which renders all persons, who possess this natural repository of moral knowledge, accountable to transcendent standards of virtue. It follows that when we overlay this ‘continuum’2 onto a constitutional framework, we place the priority, not on the individual rights of the citizen, but on the responsibilities of all political actors whereby others precede the self and the common good prevails over self-interest.

Ethical Challenges for Human–Agent Interaction in Virtual Collaboration at Work

In virtual collaboration at the workplace, a growing number of teams apply supportive conversational agents (CAs). They take on different work-related tasks for teams and single users such as scheduling meetings or stimulating creativity. Previous research merely focused on these positive aspects of introducing CAs at the workplace, omitting ethical challenges faced by teams using these often artificial intelligence (AI)-enabled technologies. Thus, on the one hand, CAs can present themselves as benevolent teammates, but on the other hand, they can collect user data, reduce worker autonomy, or foster social isolation by their service. In this work, we conducted 15 expert interviews with senior researchers from the fields of ethics, collaboration, and computer science in order to derive ethical guidelines for introducing CAs in virtual team collaboration. We derived 14 guidelines and seven research questions to pave the way for future research on the dark sides of human–agent interaction in organizations.

The European Union One Health 2022 Zoonoses Report.

This report by the European Food Safety Authority and the European Centre for Disease Prevention and Control presents the results of the zoonoses monitoring and surveillance activities carried out in 2022 in 27 Member States (MSs), the United Kingdom (Northern Ireland) and 11 non-MSs. Key statistics on zoonoses and zoonotic agents in humans, food, animals and feed are provided and interpreted historically. In 2022, the first and second most reported zoonoses in humans were campylobacteriosis and salmonellosis, respectively. The number of cases of campylobacteriosis and salmonellosis remained stable in comparison with 2021. Nineteen MSs and the United Kingdom (Northern Ireland) achieved all the established targets in poultry populations for the reduction of Salmonella prevalence for the relevant serovars. Salmonella samples from carcases of various animal species, and samples for Campylobacter quantification from broiler carcases, were more frequently positive when performed by the competent authorities than when own checks were conducted. Yersiniosis was the third most reported zoonosis in humans, followed by Shiga toxin-producing Escherichia coli (STEC) and Listeria monocytogenes infections. L. monocytogenes and West Nile virus infections were the most severe zoonotic diseases, with the most hospitalisations and highest case fatality rates. In 2022, reporting showed an increase of more than 600% compared with 2021 in locally acquired cases of human West Nile virus infection, which is a mosquito-borne disease. In the EU, the number of reported foodborne outbreaks and cases, hospitalisations and deaths was higher in 2022 than in 2021. The number of deaths from outbreaks was the highest ever reported in the EU in the last 10 years, mainly caused by L. monocytogenes and to a lesser degree by Salmonella. Salmonella and in particular S. Enteritidis remained the most frequently reported causative agent for foodborne outbreaks. Norovirus (and other calicivirus) was the agent associated with the highest number of outbreak human cases. This report also provides updates on brucellosis, Coxiella burnetii (Q fever), echinococcosis, rabies, toxoplasmosis, trichinellosis, infection with Mycobacterium tuberculosis complex (focusing on Mycobacterium bovis and Mycobacterium caprae) and tularaemia.

Abstract LB_B24: Validating novel therapeutic antibodies for targeting head & neck squamous cell malignancies

Abstract Introduction: Head and Neck Squamous Cell Carcinoma (HNSCC) encompasses cancers of the lips, oral cavity, larynx, pharynx, and salivary glands. The prevalence of HNSCC is approximately 890,000 new cancer cases per year, with a mortality rate of 450,000, making it the 7th most common cancer worldwide. Standard-of-care treatments involve surgery and conventional chemotherapy, underscoring the necessity for novel and effective targeted therapeutic interventions. The aim of my study was to determine whether the cancer stem cell marker LGR5 (leucine-rich repeat-containing G-protein receptor 5) is overexpressed in HNSCC, in order to validate our novel and highly specific LGR5 antibody (α-LGR5) as an effective diagnostic and therapeutic agent. Objectives:1. Develop a fluorescently labeled version of α-LGR5. 2. Characterize LGR5 expression in HNSCC cell lines using western blot and immunofluorescence, relative to colorectal cancer cell lines that have previously demonstrated high LGR5 levels. 3. Establish a biobank of patient-derived HNSCC organoids for future functional studies of α-LGR5 in therapeutic applications. Results: LGR5 expression was assessed in HNSCC cell lines including SCC-61 (tongue), SCC-15 (tongue), and FaDu (hypopharyngeal), as well as other cancer cell lines using western blotting (see Figure 1). Additionally, high levels of LGR5 were observed using the fluorescently labeled α-LGR5, with a localization pattern consistent with previous findings – minimal cell surface staining, and LGR5 primarily concentrated within intracellular puncta (see Figure 2). Organoids were successfully derived from two patient biopsy samples, albeit with varying success rates; none of the biopsied 'healthy' margin tissues yielded organoids, while only one of the HNSCC samples formed organoids (see Figure 3). Conclusion: LGR5 continues to emerge as a promising diagnostic and therapeutic target across various cancers. The data from this study suggests that this includes HNSCC in the tongue and hypopharyngeal tissue. Earlier research in the de la Roche lab using α-LGR5 indicates that the LGR5 protein undergoes rapid internalization, accounting for its predominant internalized punctate distribution (doi: https://doi.org/10.1101/2022.09.01.506182). The hypothesis proposes that α-LGR5, as an antibody-drug conjugate (ADC), represents an ideal approach for targeting cancer cells with heightened LGR5 expression, thereby raising the intriguing prospect of a highly effective therapeutic strategy for HNSCC. Nevertheless, further experiments are warranted to assess the efficacy of α-LGR5 as a potential therapeutic agent in humans. With the demonstrated potential of an HNSCC organoid biobank, as indicated by the results of this study, there are substantial opportunities for conducting representative functional experiments to advance α-LGR5 ADCs into clinical studies. Overall, the findings of this project offer significant motivation to continue investigating the potential of α-LGR5 and patient-derived cancer organoids. Citation Format: Ameer S Basta, Marc de la Roche. Validating novel therapeutic antibodies for targeting head & neck squamous cell malignancies [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2023 Oct 11-15; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2023;22(12 Suppl):Abstract nr LB_B24.

Decentring critical theory with the help of critical theory: Ecocide and the challenge of anthropocentricism

Our present situation of anthropogenic ecological disaster calls on Western philosophy in general, and Frankfurt School critical theory in particular, to reconsider some long-standing, entrenched assumptions concerning what it means to be a human agent and to relate to other agents. In my article, I take up the challenge in dialogue with the idea of critical theory articulated by Max Horkheimer in the 1930s. My overall concern is to contribute to on-going efforts to decentre Frankfurt School critical theory in multiple dimensions. With the help of Horkheimer, I seek to show that this theoretical tradition has itself an important contribution to make to the endeavour. In Section 1, I argue that the methodology he advocates for critique of society offers a view of the relationship between the human mind and reality, as well as of humans with other humans, that avoids dogmatic rigidity and is hospitable towards mutual learning through engagement with other philosophical and cultural traditions. In Section 2, I consider the more specific challenge of anthropocentrism, suggesting the need for a more differentiated account of this. While critical theory is unavoidably anthropocentric in certain respects, it could avoid more pernicious forms of anthropocentrism that establish epistemic and ethical hierarchies between humans and other-than-human entities and that conceive of ethical validity as a purely human construction, with no independence of human needs and concerns.

The digital turn in memory studies

This article examines the changes experienced by collective memory in the digital era. Contrary to the thesis that digital memory entails a new type of memory, which is radically different from the traditional conceptualization, I argue that the practice of digital memory materializes and implements the theoretical claims made by Memory Studies since the field’s inception – collective memory conceived as a process, mediated and remediated by multiple media, with the participation of dynamic communities that perform rather than represent the past. In the article, I address what I propose are the following four major transformations that collective memory has undergone in the digital era: (1) the new ontology of the digital archive; (2) the shift from narrative as a privileged form of collective memory to the cultural form of the database; (3) the reconfiguration of agency, in which a distributed memory is performed by human and non-human agents in a dynamic entanglement; and (4) the shift from mnemonic objects to mnemonic assemblages, comprising persons, things, artefacts, spaces, discourses, behaviours and expressions in dynamic relatedness.

Abstract C111: A novel human monoclonal antibody targeting active ADAM10 demonstrates anti-tumor effects in colorectal cancer

Abstract Colorectal cancer (CRC) is the third most diagnosed cancer in the USA and accounts for more than 600,000 deaths annually worldwide, primarily due to relapse with highly aggressive, chemo-resistant disease characterized by poorly differentiated cancer cells with stem cell-like properties. A common signature of these chemo-resistant tumors is dysregulation of Notch receptor signaling, as well as upregulation of its metalloprotease activator, ADAM10. Although small molecule inhibition of either Notch or ADAM10 has been shown to produce potent anti-tumor effects, these therapeutic strategies have failed in clinical trials primarily due to systemic toxicities, especially cytotoxic effects on the gastrointestinal tract and musculoskeletal system, highlighting the need for development of more targeted approaches. We have previously demonstrated that ADAM10 predominantly exists in an inhibited state in normal tissues but is activated in tumor cells through a conformational change in the extracellular domain, thus providing a potential target for tumor-specific modulation of ADAM10 activity. Here, we look to characterize a novel human monoclonal antibody agent (1H5) that selectively targets an exposed extracellular region of activated ADAM10 on tumor cells. We previously demonstrated that treatment with a murine version of the antibody (8C7), specific for the activated form of both mouse and human ADAM10, conferred a significant reduction in tumor burden against human CRC cell lines in cell culture and transplants in xenograft models, and relapse was prevented when 8C7 was combined with chemotherapy. Here, we demonstrate that the 1H5 monoclonal antibody effectively reduces cell viability in numerous colorectal cancer cell lines in vitro and induces marked tumor regression in established xenograft models through inhibition of Notch signaling. Through the use of additional genetic tools combined with in vitro and in vivo models, our preclinical study aims to fully evaluate 1H5 as novel therapeutic agent to treat aggressive colorectal cancer. We aim to propel this novel agent toward clinical-stage development. Citation Format: Pargol Mashati, Dan Sun, Eduardo Garcia Reino, Jessica A. Blandino, Ben Mason, Nayanendu Saha, Dimitar B. Nikolov, Prem Premsrirut. A novel human monoclonal antibody targeting active ADAM10 demonstrates anti-tumor effects in colorectal cancer [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2023 Oct 11-15; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2023;22(12 Suppl):Abstract nr C111.