Specific Project Research Articles

P4PC: A Portal for Bioinformatics Resources of piRNAs and circRNAs

Background: PIWI-interacting RNAs (piRNAs) and circular RNAs (circRNAs) are two kinds of non-coding RNAs (ncRNAs) that play important roles in epigenetic regulation, transcriptional regulation, post-transcriptional regulation of many biological processes. Although there exist various resources, it is still challenging to select such resources for specific research projects on ncRNAs. Methods: In order to facilitate researchers in finding the appropriate bioinformatics sources for studying ncRNAs, we created a novel portal named P4PC that provides computational tools and data sources of piRNAs and circRNAs. Results: 249 computational tools, 126 databases and 420 papers are manually curated in P4PC. All entries in P4PC are classified in 5 groups and 26 subgroups. The list of resources is summarized in the first page of each group. Conclusion: According to their research proposes, users can quickly select proper resources for their research projects by viewing detail information and comments in P4PC. Database URL is http://www.ibiomedical.net/Portal4PC/ and https://43.138.46.5/Portal4PC/.

SpinalTRAQ: A novel volumetric cervical spinal cord atlas identifies the corticospinal tract synaptic projectome in healthy and post-stroke mice.

Descending corticospinal tract (CST) connections to the neurons of the cervical spinal cord are vital for performance of forelimb-specific fine motor skills. In rodents, CST axons are almost entirely crossed at the level of the medullary decussation. While specific contralateral axon projections have been well-characterized using anatomic and molecular approaches, the field currently lacks a cohesive imaging modality allowing rapid quantitative assessment of the entire, bilateral cervical cord projectome at the level of individual laminae and cervical levels. This is potentially important as the CST is known to undergo marked structural remodeling in development, injury, and disease. We developed SpinalTRAQ (Spinal cord Tomographic Registration and Automated Quantification), a novel volumetric cervical spinal cord atlas and machine learning-driven microscopy acquisition and analysis pipeline that uses serial two-photon tomography- images to generate unbiased, region-specific quantification of the fluorescent pixels of anterograde AAV-labeled CST pre-synaptic terminals. In adult mice, the CST synaptic projectome densely innervates the contralateral hemicord, particularly in laminae 5 and 7, with sparse, monosynaptic input to motoneurons in lamina 9. Motor pools supplying axial musculature in the upper cervical cord are bilaterally innervated. The remainder of the ipsilateral cord has sparse labeling in a distinct distribution compared to the contralateral side. Following a focal stroke of the motor cortex, there is a complete loss of descending corticospinal axons from the injured side. Consistent with prior reports of axon collateralization, the CST spinal projectome increases at four weeks post-stroke and continues to elevate by six weeks post stroke. At six weeks post-stroke, we observed striking synapse formation in the denervated hemicord from the uninjured CST in a homotopic distribution. Additionally, CST synaptic reinnervation increases in the denervated lamina 9 in nearly all motoneuron pools, exhibiting novel patterns of connectivity. Detailed level- and lamina-specific quantification of the bilateral cervical spinal cord synaptic projectome reveals previously undescribed patterns of CST connectivity in health and injury-related plasticity.

Sinkhorn Distance Minimization for Adaptive Semi-Supervised Social Network Alignment.

Social network alignment, aiming at linking identical identities across different social platforms, is a fundamental task in social graph mining. Most existing approaches are supervised models and require a large number of manually labeled data, which are infeasible in practice considering the yawning gap between social platforms. Recently, isomorphism across social networks is incorporated as complementary to link identities from the distribution level, which contributes to alleviating the dependency on sample-level annotations. Adversarial learning is adopted to learn a shared projection function by minimizing the distance between two social distributions. However, the hypothesis of isomorphism might not always hold true as social user behaviors are generally unpredictable, and thus a shared projection function is insufficient to handle the sophisticated cross-platform correlations. In addition, adversarial learning suffers from training instability and uncertainty, which may hinder model performance. In this article, we propose a novel meta-learning-based social network alignment model Meta-SNA to effectively capture the isomorphism and the unique characteristics of each identity. Our motivation lies in learning a shared meta-model to preserve the global cross-platform knowledge and an adaptor to learn a specific projection function for each identity. Sinkhorn distance is further introduced as the distribution closeness measurement to tackle the limitations of adversarial learning, which owns an explicitly optimal solution and can be efficiently computed by the matrix scaling algorithm. Empirically, we evaluate the proposed model over multiple datasets, and the experimental results demonstrate the superiority of Meta-SNA.

Spatial dynamics of mammalian brain development and neuroinflammation by multimodal tri-omics mapping.

The ability to spatially map multiple layers of the omics information over different time points allows for exploring the mechanisms driving brain development, differentiation, arealization, and alterations in disease. Herein we developed and applied spatial tri-omic sequencing technologies, DBiT ARP-seq (spatial ATAC-RNA-Protein-seq) and DBiT CTRP-seq (spatial CUT&Tag-RNA-Protein-seq) together with multiplexed immunofluorescence imaging (CODEX) to map spatial dynamic remodeling in brain development and neuroinflammation. A spatiotemporal tri-omic atlas of the mouse brain was obtained at different stages from postnatal day P0 to P21, and compared to the regions of interest in the human developing brains. Specifically, in the cortical area, we discovered temporal persistence and spatial spreading of chromatin accessibility for the layer-defining transcription factors. In corpus callosum, we observed dynamic chromatin priming of myelin genes across the subregions. Together, it suggests a role for layer specific projection neurons to coordinate axonogenesis and myelination. We further mapped the brain of a lysolecithin (LPC) neuroinflammation mouse model and observed common molecular programs in development and neuroinflammation. Microglia, exhibiting both conserved and distinct programs for inflammation and resolution, are transiently activated not only at the core of the LPC lesion, but also at distal locations presumably through neuronal circuitry. Thus, this work unveiled common and differential mechanisms in brain development and neuroinflammation, resulting in a valuable data resource to investigate brain development, function and disease.

Spatial dynamics of mammalian brain development and neuroinflammation by multimodal tri-omics mapping.

The ability to spatially map multiple layers of the omics information over different time points allows for exploring the mechanisms driving brain development, differentiation, arealization, and alterations in disease. Herein we developed and applied spatial tri-omic sequencing technologies, DBiT ARP-seq (spatial ATAC-RNA-Protein-seq) and DBiT CTRP-seq (spatial CUT&Tag-RNA-Protein-seq) together with multiplexed immunofluorescence imaging (CODEX) to map spatial dynamic remodeling in brain development and neuroinflammation. A spatiotemporal tri-omic atlas of the mouse brain was obtained at different stages from postnatal day P0 to P21, and compared to the regions of interest in the human developing brains. Specifically, in the cortical area, we discovered temporal persistence and spatial spreading of chromatin accessibility for the layer-defining transcription factors. In corpus callosum, we observed dynamic chromatin priming of myelin genes across the subregions. Together, it suggests a role for layer specific projection neurons to coordinate axonogenesis and myelination. We further mapped the brain of a lysolecithin (LPC) neuroinflammation mouse model and observed common molecular programs in development and neuroinflammation. Microglia, exhibiting both conserved and distinct programs for inflammation and resolution, are transiently activated not only at the core of the LPC lesion, but also at distal locations presumably through neuronal circuitry. Thus, this work unveiled common and differential mechanisms in brain development and neuroinflammation, resulting in a valuable data resource to investigate brain development, function and disease.

Early cortical GABAergic interneurons determine the projection patterns of L4 excitatory neurons.

During cerebral cortex development, excitatory pyramidal neurons (PNs) establish specific projection patterns while receiving inputs from GABAergic inhibitory interneurons (INs). Whether these inhibitory inputs can shape PNs' projection patterns is, however, unknown. While layer 4 (L4) PNs of the primary somatosensory (S1) cortex are all born as long-range callosal projection neurons (CPNs), most of them acquire local connectivity upon activity-dependent elimination of their interhemispheric axons during postnatal development. Here, we demonstrate that precise developmental regulation of inhibition is key for the retraction of S1L4 PNs' callosal projections. Ablation of somatostatin INs leads to premature inhibition from parvalbumin INs onto S1L4 PNs and prevents them from acquiring their barrel-restricted local connectivity pattern. As a result, adult S1L4 PNs retain interhemispheric projections responding to tactile stimuli, and the mice lose whisker-based texture discrimination. Overall, we show that temporally ordered IN activity during development is key to shaping local ipsilateral S1L4 PNs' projection pattern, which is required for fine somatosensory processing.

Algebraic classification of 2+1 geometries: a new approach

We present a convenient method of algebraic classification of 2+1 spacetimes into the types I, II, D, III, N and O, without using any field equations. It is based on the 2+1 analogue of the Newman–Penrose curvature scalars ΨA of distinct boost weights, which are specific projections of the Cotton tensor onto a suitable null triad. The algebraic types are then simply determined by the gradual vanishing of such Cotton scalars, starting with those of the highest boost weight. This classification is directly related to the specific multiplicity of the Cotton-aligned null directions and to the corresponding Bel–Debever criteria. Using a bivector (that is 2-form) decomposition, we demonstrate that our method is fully equivalent to the usual Petrov-type classification of 2+1 spacetimes based on the eigenvalue problem and determining the respective canonical Jordan form of the Cotton–York tensor. We also derive a simple synoptic algorithm of algebraic classification based on the key polynomial curvature invariants. To show the practical usefulness of our approach, we perform the classification of several explicit examples, namely the general class of Robinson–Trautman spacetimes with an aligned electromagnetic field and a cosmological constant, and other metrics of various algebraic types.

Common Fixed-Point Theorem and Projection Method on a Hadamard Space

In this paper, we obtain an equivalent condition to the existence of a common fixed point of a given family of nonexpansive mappings defined on a Hadamard space. Moreover, if the space is bounded, we show that the generating process of the approximate sequence by a specific projection method will stop in finite steps if there is no common fixed point. It is a significant advantage to reveal the nonexistence of a common fixed point in a finite time.

Pakistan's Response to International Commitments Regarding Women's Rights: A Case Study of the 4th UPR Cycle

Using the 4th UPR cycle as a contextual inquiry, this pilot project seeks to investigate Pakistan's approach to addressing global commitments on women's rights. The purpose of this study is to examine Pakistan's efforts to promote gender equality and inclusion of women and to assess how the nation has implemented the recommendations of the fourth UPR cycle. The researcher thoroughly reviewed the exercises and efforts undertaken by Pakistan to improve women's liberties, especially due to the recommendations made by the fourth UPR cycle. Its experts likely understood what these plans meant for women in Pakistan based on the specific strategies and projections that were formulated. The finding helped to determine the main components that hindered or affected the fruitful implementation of these commitments during the fourth UPR cycle. Furthermore, this study explored the manners through which grassroots developments and general society groups have fought for women's emancipation in Pakistan.

Prefrontal control of superior colliculus modulates innate escape behavior following adversity

Innate defensive responses, though primarily instinctive, must also be highly adaptive to changes in risk assessment. However, adaptive changes can become maladaptive, following severe stress, as seen in posttraumatic stress disorder (PTSD). In a series of experiments, we observed long-term changes in innate escape behavior of male mice towards a previously non-threatening stimulus following an adverse shock experience manifested as a shift in the threshold of threat response. By recording neural activity in the superior colliculus (SC) while phototagging specific responses to afferents, we established the crucial influence of input arriving at the SC from the medial prefrontal cortex (mPFC), both directly and indirectly, on escape-related activity after adverse shock experience. Inactivating these specific projections during the shock effectively abolished the observed changes. Conversely, optogenetically activating them during encounters controlled escape responses. This establishes the necessity and sufficiency of those specific mPFC inputs into the SC for adverse experience related changes in innate escape behavior.

Learning to teach with patients and caregivers: a focused ethnography

BackgroundLittle is known about what happens when patients and caregivers are involved in an academic setting as co-teachers and how healthcare professionals approach a new model of partnership-based teaching. This study aimed to explore the learning and behavioural patterns of a group of healthcare professionals who were learning to teach with patients and caregivers as co-teachers in a post-graduate course.MethodsA focused ethnographic study involving 11 health professionals was conducted. Data were collected through participatory observation during the course, individual semi-structured interviews, and a follow-up focus group. Taxonomic analysis was performed.ResultsThree categories were identified: ‘group’, ‘role of narration’ and ‘applying co-teaching with patients and caregivers ’. Specifically, heterogeneity, absence of hierarchies, and balanced relationships characterised the group dynamic and promoted partnership. Narration played a key role both in learning and in healthcare professionals’ relationship with patients and caregivers and promoted emotional skills and self-awareness. Project planning and lessons simulations were essential aspects of the implementation process.ConclusionsThis focused ethnography helped further understanding of the context of a specific project involving patients and caregivers as co-teachers in healthcare professional education. The development of emotional skills and self-awareness are the main learning patterns of co-teaching, and interprofessionalism and balanced relationships are the basis of the behavioural patterns. These patterns facilitated the involvement of patients and caregivers in health education.

China’s Defense Cooperation with Latin America and Caribbean: Trends and Limitations

Introduction. China started to develop military-to-military ties and defense-industrial cooperation with Latin America and Caribbean countries in the early 2000s as an element of its strategy of comprehensive cooperation with the region. Defense cooperation was mentioned in the Chinese documents and statements on the policy in the region from the early 2000s. However, China has always considered this defense cooperation to be just a secondary, subordinate element of its overall strategy in the region. Methods. The article is based on Chinese publications, statements, and documents concerning China’s policies in defense cooperation with the region, as well as on Latin American and other Western publications on specific cooperation projects. The author compares the Chinese approach to defense cooperation with Latin America to similar Chinese cooperation policies in other regions, especially in Africa. Analysis.China views defense cooperation with Latin America as a subordinate element of its general strategy of economic and political presence in the region. Cultivating ties with the local military elites of Latin America is especially emphasized, and the exchange of military delegations started in the early 2000s. To boost defense cooperation, China is sometimes ready to provide significant military assistance to the region. China has established permanent mechanisms of defense dialogue with the regional countries in the form of regular forums and conferences. Other important venues of military cooperation include personnel training, joint exercises, and the region’s visits by Chinese warships. China has managed to establish a presence on the arms market in Latin America in the 2000s but has failed to become a major weapons provider in the region. Currently, Chinese arms sales in Latin America are in decline. However, China has achieved major results in the development of dual-use technology cooperation with the LAC countries, especially in the fields of space and internal security. That may create preconditions for faster development of military and military technical cooperation between China and Latin America in the future. So far, the Chinese approach to defense cooperation in the region remains more cautious and gradual compared to cooperation with Africa. China is reluctant to challenge the US red lines here. That may change in the future as China-US relations continue to deteriorate. Authors contributions. Ekaterina Kosevich was responsible for researching and covering the development of political relations between China and Latin America. Vasily Kashin touched on cooperation in defense, the security industry, and dual-use technology.

A User Evaluation of a Collaborator Recommender based on Co-Changed Files

Active collaboration is essential for the success of software projects across the development life-cycle. Unfortunately, in social coding platforms, such as GitHub, it is still challenging for developers to identify potential collaborators with whom they could engage to create new/stronger ties and enhance the quality of contributions. To this end, we implemented developer recommendation strategies and prototype tool to help project contributors improve their collaborations. Thus, in this work, we described a controlled experimental study concerned usability and user satisfaction to investigate the developers’ perceptions of using CoopFinder, a prototype tool to support two strategies for recommending collaborations. These developer recommendation strategies aim to connect developers of a specific project based on their similar interests. The study involved 35 participants, 18 of which were GitHub users, and 17 were non–GitHub users. We asked participants to perform the experiment tasks to find collaborators with similar interests using a prototype recommendation tool and GitHub. We reported a quantitative and qualitative evaluation of strategies and tool using the state of the practice as a baseline. As a result, we observed that recommender based on co–changed files can provide suitable collaborator recommendations to developers of a specific project. About 66% of the participants confirmed they would use or recommend this tool.

Change as a Scientific Enterprise: Practical Suggestions about Using Change Theory.

Change theory has increasingly become an area of scholarship in STEM education. While this area has traditionally been a topic for organizational psychology, business management, communication studies, and higher education, STEM education researchers are increasingly aware of the need to use formal theories to guide change efforts and research. Formal change theory encompasses our current research-based knowledge about how and why change occurs, and therefore, can guide the selection and design of promising interventions. Yet learning about and using theory is challenging because many of us have no formal training in this area and relevant scholarship comes from many different disciplines. Inconsistent terminology creates an additional barrier. Thus, this essay aims to contribute to a common lexicon in STEM higher educational change efforts by clearly distinguishing between formalized change theory, which emerges from research, and a theory of change, which guides the logic of a specific project. We also briefly review the current state of the field regarding the use of formal change theory and provide examples of how change theory has been used in biology education. Lastly, we offer practical guidance for researchers and change agents who wish to more intentionally and effectively use change theory in their work.

Montage as process of knowledge mobilization in architectural design

Drawing on findings from an ethnographic study, the paper at hand provides an example of a pronounced way of working with montage as a means of mobilizing knowledge in the architectural design process. With reference to a specific design project, the paper follows architecture students systematically exploring and structuring the problem’s space of possibilities by applying montage. Highlighting the methodological rigor and logical coherence their procedure involves, the paper elaborates on montage as an effective method and traceable exploratory process. Presenting and discussing this empirical data, the paper aims at showing how montage allows for apprehending a problem in a holistic manner while at the same time facilitating its analysis into separate parts. In this way, montage engenders the mobilization of knowledge, which can be implicated to the case at hand.

Perspectives of COPD patients, publicly funded scientists, and industry representatives on responsibility and stakeholder engagement in drug discovery research

ABSTRACT Ensuring societal influence in research and innovation through stakeholder engagement is vital in the Responsible Research and Innovation (RRI) framework. By studying a drug discovery project, we examine how stakeholders can influence drug discovery and development meaningfully. Through semi-structured interviews, we explore: How do patients as potential users of a new drug, the scientists who discover it, and the industry that might develop it, think about responsibility and stakeholder engagement in drug discovery? Most of the responses voiced by our informants about responsibility and stakeholder engagement relate to the broader institutional and political context of health-related innovation, rather than the specific research project. We argue, that in order to make stakeholder engagement work within some forms of drug discovery research, it should be used as a forum for mobilizing political and organizational debate, taking critical dialogues beyond project-specific engagement in innovation.

Constructed wetlands as nature based solutions – hands-on activities to highlight their potential to minimize ocean pollution

This work presents an engaging hands-on activity designed to teach school students about nature based solutions (NBS) and their role in achieving high-quality water systems within a sustainable circular economy. Through this activity, students actively participate in building a small constructed wetland (CW) and test its effectiveness under various contamination scenarios. The activity was tested with school teachers, undergoing refinements based on their feedback. This iterative development process has ensured the activity’s effectiveness in engaging both school students and the public. Further, the CW model can be scaled-up for specific school projects focused on improving water quality. This activity offers valuable opportunities to enhance ocean literacy, promote understanding on NBS and raise awareness about aquatic ecosystems contamination and the importance of environmental sustainability.

Convergence analysis of virtual element method for the electric interface model on polygonal meshes with small edges

A conforming virtual element method is studied for approximating the solution of a pulsed electric interface model on polygonal meshes with small edges or faces, which traditional virtual and finite element methods cannot easily handle. One of the significant advantages of this virtual element method is to generate interface-conforming meshes efficiently exploiting polygonal meshes and hanging nodes. The virtual element method employs specific projection operators to establish optimal error estimates with reasonable assumptions regarding the solution's regularity. The voltage potential of the pulsed electric model through the physical media is approximated by using a fully discrete virtual element approach based on Crank-Nicolson temporal discretization. Numerical examples are used to illustrate the expected order of convergence. The efficiency and robustness of the proposed method are displayed on interface-independent/dependent background-fitted meshes with small edges and large magnitudes of discontinuities across the interface by these experiments.

Instantaneous nostalgia for the future: 10,000 postcards for 2042

This article focuses on analogue postcards as a communicative and artistic tool for potentially engaging nostalgically with the past, present, and future. It poses questions about the experience of time and place in a specific setting (the city of Montreal, Canada), as well as in a specific project that looks at cultural mediation in public spaces. During the summer of 2017, Comptoir public, an organization that works with artists and cultural mediators, launched the project “Postes du futur” ( Mail from the Future). The organizers asked Montrealers to write a postcard to a recipient of the sender's choosing, so that it will be mailed in 2042 during the celebration of Montreal's 400th anniversary (i.e., 25 years later). One of our main findings is that most of these postcards will be sent to the current addresses of future recipients. Choosing one's home as one of the settings to write to and to write about finally made it possible to connect to the historical and medical meaning of nostalgia: the homesickness, the yearning for a place of one's own, for a space we now miss prospectively on in the future. Home, where people live their lives, is not yet “lost” or “left behind.” But anticipating its loss and transfer to others becomes one of the primordial factors shaping instantaneous nostalgia and its expression—a future in which postcard senders are no longer present or even alive. The issue of the finiteness and the irreversibility of time is usually an indicator of past-oriented nostalgia. In our case, it is projected toward the future. The printed, analogue postcard becomes the writing space that leaves room for anticipated and anticipatory nostalgia and for imagining future communication technologies.

An Exploration of Artistic Expressions of Everyday Peri-Urban Landscapes as a Method of Socio-Spatial Analysis in Spatial Planning

Everyday landscapes, including peri-urban areas, play a pivotal role in shaping our physical and mental environments. Nevertheless, spatial planning often falls short of integrating contemporary everyday life and lived space. This paper advocates for an expanded approach beyond traditional planning methods, exploring the potential of artistic representations like drawings, photographs, and films to capture the nuances of peri-urban landscapes. Based on a selection of contemporary artistic works in the fields of drawing, photography, and cinema, this paper explores, through an analysis of specific projects and interviews with the artists, the potentials and constraints of these types of representations. This analysis of selected works reveals that these mediums embody a rich and complex collective journey, showcasing the profound connection between the artist and the environment. Structured around the key stages of analysis, documentation, and communication, the discussion elucidates the interrelated nature of these phases within a broader creative process. It underscores the significance of recognizing these artistic representations as integral components in planning processes, emphasizing their potential to provide unique insights into the complexities of peri-urban landscapes. In conclusion, this article proposes a set of recommendations for the incorporation of these artistic mediums within planning processes and urban studies.