Development Of Activity Research Articles

Antitumor activity of Z15-0-2, a bispecific nanobody targeting PD-1 and CTLA-4

The combination of programmed cell death protein 1 (PD-1) and cytotoxic T lymphocyte antigen 4 (CTLA-4) antibodies has potential for enhancing clinical efficacy. We described the development and antitumor activity of Z15-0, a bispecific nanobody targeting both the PD-1 and CTLA-4 pathways simultaneously. We designed and optimized the mRNA sequence encoding Z15-0, referred to as Z15-0-2 and through a series of in vitro and in vivo experiments, we established that the optimized Z15-0-2 mRNA sequence significantly increased the expression of the bispecific nanobody. Administration of Z15-0-2 mRNA to tumor-bearing mice led to greater inhibition of tumor growth compared to controls. In aggregate, we introduced a novel bispecific nanobody and have re-engineered it to boost expression of mRNA, representing a new drug development paradigm.

Study on the Effects of Different Light Supply Modes on the Development and Extracellular Enzyme Activity of Ganoderma lucidum

Study on the Effects of Different Light Supply Modes on the Development and Extracellular Enzyme Activity of Ganoderma lucidum

Network state transitions during cortical development.

Mammalian cortical networks are active before synaptogenesis begins in earnest, before neuronal migration is complete, and well before an animal opens its eyes and begins to actively explore its surroundings. This early activity undergoes several transformations during development. The most important of these is a transition from episodic synchronous network events, which are necessary for patterning the neocortex into functionally related modules, to desynchronized activity that is computationally more powerful and efficient. Network desynchronization is perhaps the most dramatic and abrupt developmental event in an otherwise slow and gradual process of brain maturation. In this Review, we summarize what is known about the phenomenology of developmental synchronous activity in the rodent neocortex and speculate on the mechanisms that drive its eventual desynchronization. We argue that desynchronization of network activity is a fundamental step through which the cortex transitions from passive, bottom-up detection of sensory stimuli to active sensory processing with top-down modulation.

Development-induced dispossession: Adivasi existence in the milieu of contemporary Indian texts in translation

The paradigms of development around the globe involves mechanisms associated with its social purpose, which is more often than not dubious in nature! Natural resources form the fundamental aspect of any developmental activity. But in the process of accumulating these resources, the beneficiaries often rely on malignant mechanisms. The capitalist discourse has always been successful in manifesting their agendas of development as constructive and profitable for the entire humanity. Periodically, when the utility of development is foregrounded by dominant cultural forms, often the ramifications of progress remain uncritiqued. The developmental projects earmarked for the rural population remain unnoticed, for it serves the interest of the elite and the urban middle class. Many a time, the indigenous population, who inhabit the resource rich area are swayed away by the false propaganda for development, ultimately aggravating their existing deprivation. In the case of India, too, amidst all the development activities, the marginalized populace or the so-called Adivasis are the worst sufferers, because they have been encountering displacement for ages. The current study attempts to unveil the displacement of the tribal population (Adivasi) of India due to development projects, thereby offering a critical analysis of the social policies. The study employs select translated literary narratives to examine the development-induced dispossession of tribal population in the colonial, postcolonial and neo-liberal phase of Indian history, adopting the theoretical framework of new historicism.

Ciliogenesis defects after neurulation impact brain development and neuronal activity in larval zebrafish

Cilia are slender, hair-like structures extending from cell surfaces and playing essential roles in diverse physiological processes. Within the nervous system, primary cilia contribute to signaling and sensory perception, while motile cilia facilitate cerebrospinal fluid flow. Here, we investigated the impact of ciliary loss on neural circuit development using a zebrafish line displaying ciliogenesis defects. We found that cilia defects after neurulation affect neurogenesis and brain morphology, especially in the cerebellum, and lead to altered gene expression profiles. Using whole brain calcium imaging, we measured reduced light-evoked and spontaneous neuronal activity in all brain regions. By shedding light on the intricate role of cilia in neural circuit formation and function in the zebrafish, our work highlights their evolutionary conserved role in the brain and sets the stage for future analysis of ciliopathy models.

Exploratory and exploitative linkages and innovative activity in the offshore renewable energy sector

PurposeThis paper examines the relationship between open innovation (measured by exploratory and exploitative linkages) and firm-level innovative activity in the offshore renewable energy (ORE) sector.Design/methodology/approachA unique, purpose-built survey that targeted firms operating in the ORE sector and its supply chain was used. The data provides novel insights into the research activities and networking capabilities of an industry in its infant stages of development. Regression models are used to estimate the relationship between firm-level external linkages and innovative activity.FindingsExploratory linkages are positively related to more innovative activity. This relationship is subject to diminishing returns, distinguishing the ORE sector from other sectors. Collaborating with suppliers and accessing scientific journals are conducive to research and development (R&D) activity and process innovation, whilst collaborating with customers is associated with the decision to introduce new products and processes.Originality/valueThis study provides evidence of a positive, but curvilinear, relationship between external knowledge linkages and innovative activity, adding novel insights into the relationship between open innovation (OI) strategies, research and innovation outcomes for firms predominantly in the introductory stages of the technological life cycle with limited commercialisation experience. The nuanced finding that specific linkages matter for certain research and innovation (R&I) outcomes adds deeper complexity to March’s (1991) framework, where tailoring certain exploratory or exploitative linkages to specific innovation activities is important.

A Transcriptomic Analysis Sheds Light on the Molecular Regulation of Wood Formation in Populus trichocarpa during Drought Stress

Wood is an abundant and essential renewable resource whose production is threatened in some parts of the world by drought. A better understanding of the molecular mechanisms underlying wood formation during drought is critical to maintaining wood production under increasingly adverse environmental conditions. In this study, we investigated wood formation in black cottonwood (Populus trichocarpa) during drought stress. The morphological changes during drought stress in P. trichocarpa included the wilting and drooping of leaves, stem water loss, and a reduction in whole plant biomass. The water embolism rate indicated that the water transport in stems was blocked under drought conditions. An anatomical analysis of the xylem and cambium revealed that drought stress changed the structure of vessel cells, increased lignin accumulation, and decreased the cambium cell layers. We subsequently identified 12,438 and 9156 differentially expressed genes from stem xylem and cambium tissues under well-watered and drought conditions, respectively. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses revealed that these genes were mainly involved in hormone signal transduction and amino sugar and nucleotide sugar metabolism. To further explore the molecular mechanism of wood formation in response to drought, we analyzed the expression patterns of the genes involved in lignin, cellulose, and hemicellulose biosynthesis in xylem and the genes involved in cambial activity in the cambium. To better understand the regulatory networks governing xylem development and cambium activity in response to drought, we analyzed the MYB (138), AP2 (130), bHLH (89), and NAC (81) transcription factor families to shed light on the interactions between the TFs in these families and the genes they regulate. Identifying the key genes that regulate wood formation in P. trichocarpa during drought provides a genetic foundation for further research on the molecular regulatory networks and physiology underpinning wood formation during drought stress.

Indigenous values and perspectives for strengthening food security and sovereignty: learning from a community-based case study of Misko-ziibiing (Bloodvein River First Nation), Manitoba, Canada

In recent years, changing environmental, developmental activity, government policies and laws, lifestyle changes and affordability dynamics have continued to threaten the self determination and food sovereignty of Indigenous peoples in the community. Their perspectives, teachings, and voices are rarely present in any scholarly work. Despite food security being a significant challenge among many First Nations communities on Turtle Island, there needs to be more empirical, community-based research that underscores the role of traditional food systems and associated values and teachings in Manitoban communities through an Indigenous lens. This research addresses that gap by building upon Indigenous perspectives and knowledges on the status and future directions of food security and sovereignty in Misko-ziibiing (Bloodvein River First Nation). Guided by Indigenous research protocol and using a qualitative research approach, ten in-depth interviews with Bloodvein River First Nation (BVR) and Winnipeg Elders were conducted. Data was also sourced through discussions with local council members, participant observation, and field visits during 2017. The fundamental values and traditional teachings associated with food sovereignty within the community are aligned with the spirit of sharing, including sharing ethics and protocols, social learning within the community, and intergenerational transmission. Enhanced intergenerational transmission of traditional teachings, education and language revitalization, and local leadership involvement can strengthen these social and cultural values to enhance Indigenous food security and sovereignty in Misko-ziibiing. This research identifies the knowledge and views of Elders, hunters, trappers and fishers, contributing to the current studies associated with traditional food systems and teachings. Strengthening social and cultural traditions and values is vital in working toward Indigenous food governance, sovereignty, and revitalization of their Indigenous food systems.

The rising significance of the Perth Basin

Amid a nationwide struggle to revitalise exploration and development activity in the Australian oil and gas industry, the Perth Basin emerges as a beacon of hope. During 2003–2005, the basin experienced a peak in exploration activity, averaging an impressive 13 wells drilled per year. However, mirroring the sector’s broader nationwide trend, the Perth Basin then saw a decline in drilling, with an annual average of just three exploration wells over 2006–2022. Nevertheless, a turnaround is in progress, with the basin poised for the drilling of eight exploration and appraisal wells in 2024. The turning point for the basin can be traced back to the Waitsia discovery in 2014 which rekindled interest and activity in the region, resulting in nine distinct gas discoveries and a subsequent doubling of the basin’s estimated gas resources. Against the backdrop of projected gas shortfalls in Western Australia’s domestic market, players in the basin have ambitious development plans amid rising gas prices. We expect that the Perth Basin could contribute up to 30% of WA’s domestic gas supplies by 2030, compared to a modest 5% in 2023. Notably, a substantial portion of WA’s new gas supplies are expected to originate from the Perth Basin. This paper examines the resurgence of activity and interest in the Perth Basin, driven by surging valuations and its growing significance within the domestic gas market. It also examines the commercialisation pathways in light of the updated ban on onshore gas exports in WA.

The Expression of TP63 as a Biomarker of Early Recurrence in Resected Esophageal Squamous Cell Carcinoma after Neoadjuvant Chemoradiotherapy.

Esophageal cancer ranks among the ten most common cancers worldwide. Despite the adoption of neoadjuvant concurrent chemoradiotherapy (nCCRT) followed by surgery as the standard treatment approach in recent years, the local recurrence rate remains high. In this study, we employed RNA-seq to investigate distinctive gene expression profiles in esophageal squamous cell carcinoma (ESCC) with or without recurrence following a standard treatment course. Our findings indicate that recurrent ESCC exhibits heightened keratinizing and epidermis development activity compared to non-recurrent ESCC. We identified TP63 as a potential candidate for distinguishing clinical outcomes. Furthermore, immunohistochemistry confirmed the trend of TP63 overexpression in ESCC recurrence. Patients with elevated TP63 expression had poorer overall survival and lower 3-year recurrence-free survival. This study underscores the potential of TP63 as a biomarker for detecting cancer recurrence and suggests its role in guiding future treatment options.

Midbrain dopaminergic degeneration differentially modulates primary motor cortex activity and motor behavior in hemi-parkinsonian rats.

Parkinson's disease (PD) is marked by degeneration in the nigrostriatal dopaminergic pathway, affecting motor control via complex changes in the cortico-basal ganglia-thalamic motor network, including the primary motor cortex (M1). The modulation of M1 neuronal activity by dopaminergic inputs, particularly from the ventral tegmental area (VTA) and substantia nigra pars compacta (SNc), plays a crucial role in PD pathophysiology. This study investigates how nigrostriatal dopaminergic degeneration influences M1 neuronal activity in rats using in vivo calcium imaging. Histological analysis confirmed dopaminergic lesion severity, with high lesion level rats showing significant motor deficits. Levodopa treatment improved fine motor abilities, particularly in high lesion level rats. Analysis of M1 calcium signals based on dopaminergic lesion severity revealed distinct M1 activity patterns. Animals with low dopaminergic lesion showed increased calcium events, while high lesion level rats exhibited decreased activity, partially restored by levodopa. These findings suggest that M1 activity is more sensitive to transient fluctuations in dopaminergic transmission, rather than to chronic high or low dopaminergic signaling. This study underscores the complex interplay between dopaminergic signaling and M1 neuronal activity in PD symptoms development. Further research integrating behavioral and calcium imaging data can elucidate mechanisms underlying motor deficits and therapeutic responses in PD.

E-CLEAP: An ensemble learning model for efficient and accurate identification of antimicrobial peptides.

With the increasing problem of antimicrobial drug resistance, the search for new antimicrobial agents has become a crucial task in the field of medicine. Antimicrobial peptides, as a class of naturally occurring antimicrobial agents, possess broad-spectrum antimicrobial activity and lower risk of resistance development. However, traditional screening methods for antimicrobial peptides are inefficient, necessitating the development of an efficient screening model. In this study, we aimed to develop an ensemble learning model for the identification of antimicrobial peptides, named E-CLEAP, based on the Multilayer Perceptron Classifier (MLP Classifier). By considering multiple features, including amino acid composition (AAC) and pseudo amino acid composition (PseAAC) of antimicrobial peptides, we aimed to improve the accuracy and generalization ability of the identification process. To validate the superiority of our model, we employed five-fold cross-validation and compared it with other commonly used methods for antimicrobial peptide identification. In the experimental results on an independent test set, E-CLEAP achieved accuracies of 97.33% and 84% for the AAC and PseAAC features, respectively. The results demonstrated that our model outperformed other methods in all evaluation metrics. The findings of this study highlight the potential of the E-CLEAP model in enhancing the efficiency and accuracy of antimicrobial peptide screening, which holds significant implications for drug development, disease treatment, and biotechnology advancement. Future research can further optimize the model by incorporating additional features and information, as well as validating its reliability on larger datasets and in real-world environments. The source code and all datasets are publicly available at https://github.com/Wangsicheng52/E-CLEAP.

Infrastructure competitiveness of regencies and cities in Java Island

Regional infrastructure competitiveness is highly influential in regional development. This research aims to: (1) compile the infrastructure competitiveness index for regencies or cities in Java, (2) assess the level of infrastructure competitiveness disparity between regencies or cities, and (3) analyze the relationship between the regional infrastructure competitiveness index and economic growth. In investigating the regional infrastructure competitiveness index, five infrastructure groups were assessed, namely social infrastructure, information technology, transportation, economy, and culture. The infrastructure competitiveness between regions (regencies and cities) was determined by scoring and standardization. The Gibbs & Martins index was used to measure the infrastructure competitiveness gap. Meanwhile, the relationship trend between the infrastructure competitiveness index and regional economic growth was analyzed using crosstabs. For the competitiveness of regional infrastructure in Java, this research observed spatial variations between regencies or cities. Besides, the regional infrastructure competitiveness index is not distributed concentrically and tends to have a diffuse pattern. Different distributions of the competitiveness index were also observed in every group of infrastructure. In general, clusters of high infrastructure competitiveness were observed in each province on the island of Java. The Gibbs & Martins index measurement illustrates Java's high regional infrastructure gap. The gap is due to the infrastructure in development centers and activity centers not being accompanied by infrastructure development in the hinterland areas. The social infrastructure has the highest level of inequality. Besides, this research also found a different relationship between infrastructure competitiveness and economic growth in the provinces.

Temperature, not net primary productivity, drives continental-scale variation in insect flight activity.

The amount of energy available in a system constrains large-scale patterns of abundance. Here, we test the role of temperature and net primary productivity as drivers of flying insect abundance using a novel continental-scale data source: weather surveillance radar. We use the United States NEXRAD weather radar network to generate a near-daily dataset of insect flight activity across a gradient of temperature and productivity. Insect flight activity was positively correlated with mean annual temperature, explaining 38% of variation across sites. By contrast, net primary productivity did not explain additional variation. Grassland, forest and arid-xeric shrubland biomes differed in their insect flight activity, with the greatest abundance in subtropical and temperate grasslands. The relationship between insect flight abundance and temperature varied across biome types. In arid-xeric shrublands and in forest biomes the temperature-abundance relationship was indirectly (through net primary productivity) or directly (in the form of precipitation) mediated by water availability. These results suggest that temperature constraints on metabolism, development, or flight activity shape macroecological patterns in ectotherm abundance. Assessing the drivers of continental-scale patterns in insect abundance and their variation across biomes is particularly important to predict insect community response to warming conditions. This article is part of the theme issue 'Towards a toolkit for global insect biodiversity monitoring'.

Nursing Continuing Professional Development Activity: May/June 2024.

Nursing Continuing Professional Development Activity: May/June 2024.

PELATIHAN PENATAUSAHAAN POS TIKET KAWASAN WISATA ALAM SEMBALUN

Sembalun tourism area has become one of the leading tourism destination in Lombok island. Since the launch of Sembalun7Summits program, the number of tourist coming to Sembalun to experience the sensation of venturing through the beautiful landscapes has increased significantly. This has opened a wide opportunity for this agricultural village to increase its income from tourism. This activity aimed to provide the knowledge for guards of entry posts to hiking trails to help them manage and record visitor data so that they can keep track of entry charges collected from visitors. Better records of entry charges and visitors will enable the guards to manage the income they have generated in order to map the expenses needed to provide better service for visitors. These services include safety measures for visitors and improved income for not only the guards in the entry posts but also villagers in surrounding areas. The training was participated by 25 post guards from ten hiking posts and five members of the Sembalun Foundation organization which is the partner of this community development activity. After the training, the post guards made an agreement to start using the Google Form designed by our team to be used as a means to record visitor data. This form will be provided in each hiking post’s social media account where visitors can schedule and register their hiking trip.

Unveiling Growth: Do Master's Degrees Propel Professional Development for English Teachers at All Experience Levels?

Teachers, as professional educators, are supposed to keep improving their ability in the pedagogical field. The teacher development program is one of the best ways for teachers to maintain and enhance their professionalism. Motivation has become an issue that is considered crucial to teachers' involvement in teacher development programs (TPD). However, investigating novice and experienced EFL teachers' motivation in pursuing their master's degree as a form of development activity is underexplored. This research article aims to investigate novice and experienced English teachers' voices regarding their motivation in pursuing a master's degree at a postgraduate program in one of the state universities in Bandung and the comparison between the teachers in regard to their motivation. This study employed a qualitative research approach guided by a case study design with 2 novice English teachers and 3 experienced English teachers who are currently studying at a postgraduate program as the respondents. The instrument used in this study was an interview with 9 questions adapted from a conceptual framework proposed by Alghamdi (2020). The findings revealed that the EFL teachers have several types of factors in their motivation to pursue their higher education. The factors are primarily grouped into incentive and reward factors, school factors, CPD program factors, and within-teacher factors. In comparison, all respondents have quite similar motivations with no significant difference. However, one difference was found in the reward factor in which the role of the family is more motivating in novice teachers than inexperienced teachers.

Interprofessional Faculty Development on Health Disparities: Engineering a Crossover “Jigsaw” Journal Club

Medical education acknowledges our need to teach our physicians about “social determinants of health” and “health care disparities”. However, educators often lack actionable training to address this need. We describe a faculty development activity, a health disparities journal club, using the jigsaw strategy with the intent of increasing awareness, encouraging self-directed learning, and inspiring future teaching of the subject to health professional learners. We completed six workshops at six individual hospitals, with 95 total attendees in medicine and numerous other health professions. Our evaluation asked trainees to: report the number of journal articles about health disparities they had read, excluding the assigned journal club articles, in the past 12 months, and to predict future plans for reading about health disparities. In total, 28.9% responded they had “never read” a prior article on health or healthcare disparities, while 54.2% responded “1–5 articles”. Many (60%) reported they would continue to investigate this topic. Our experience has demonstrated the utility and positive impact of a “flipped classroom” jigsaw method, showing it can be used successfully in Inter-Professional (IPE) Faculty Development to increase active exposure and discussion of the content. Additionally, this method promotes individual reflection and enhances continued collective engagement.

Polyoxometalate exerts broad-spectrum activity against human respiratory viruses hampering viral entry

Human respiratory viruses have an enormous impact on national health systems, societies, and economy due to the rapid airborne transmission and epidemic spread of such pathogens, while effective specific antiviral drugs to counteract infections are still lacking. Here, we identified two Keggin-type polyoxometalates (POMs), [TiW11CoO40]8- (TiW11Co) and [Ti2PW10O40]7- (Ti2PW10), endowed with broad-spectrum activity against enveloped and non-enveloped human respiratory viruses, i.e., coronavirus (HCoV-OC43), rhinovirus (HRV-A1), respiratory syncytial virus (RSV-A2), and adenovirus (AdV-5). Ti2PW10 showed highly favorable selectivity indexes against all tested viruses (SIs >700), and its antiviral potential was further investigated against human coronaviruses and rhinoviruses. This POM was found to inhibit replication of multiple HCoV and HRV strains, in different cell systems. Ti2PW10 did not affect virus binding or intracellular viral replication, but selectively inhibited the viral entry. Serial passaging of virus in presence of the POM revealed a high barrier to development of Ti2PW10-resistant variants of HRV-A1 or HCoV-OC43. Moreover, Ti2PW10 was able to inhibit HRV-A1 production in a 3D model of the human nasal epithelium and, importantly, the antiviral treatment did not determine cytotoxicity or tissue damage. A mucoadhesive thermosensitive in situ hydrogel formulation for nasal delivery was also developed for Ti2PW10. Overall, good biocompatibility on cell lines and human nasal epithelia, broad-spectrum activity, and absence of antiviral resistance development reveal the potential of Ti2PW10 as an antiviral candidate for the development of a treatment of acute respiratory viral diseases, warranting further studies to identify the specific target/s of the polyanion and assess its clinical potential.

Molecular mechanisms regulating GROWTH-REGULATING FACTORS activity in plant growth, development, and environmental responses.

Plants rely on complex regulatory mechanisms to ensure proper growth and development. As plants are sessile organisms, these mechanisms must be flexible enough to adapt to changes in the environment. GROWTH-REGULATING FACTORS (GRFs) are plant-specific transcription factors that act as a central hub controlling plant growth and development, which offer promising biotechnological applications to enhance plant performance. Here, we analyze the complex molecular mechanisms that regulate GRFs activity, and how their natural and synthetic variants can impact on plant growth and development. We describe the biological roles of the GRFs and examine how they regulate gene expression and contribute to the control of organ growth and plant responses to a changing environment. This review focuses on the premise that unlocking the full biotechnological potential of GRFs requires a thorough understanding of the various regulatory layers governing GRF activity, the functional divergence among GRF family members, and the gene networks that they regulate.