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The inheritance and innovation of ethnic clothing are critical aspects of preserving and developing cultural heritage. As modern design demands evolve the integration of traditional ethnic clothing elements into contemporary fashion faces increasing challenges. Designers must navigate the complex task of balancing the preservation of cultural essence with modern aesthetic integration. The rise of artificial intelligence-generated content AIGC technology offers promising solutions for the innovative design and application of ethnic clothing elements. This study focuses on She ethnic group clothing and explores the application of digital generation techniques and innovative design methods through the training of Low-Rank Adaptation LoRA and Checkpoints CKPT models. A key aspect of this study is the development of a custom model based on a specialized She ethnic group clothing resource database. The clothing samples within this database were systematically categorized and annotated to facilitate the training of the LoRA and CKPT models. These models were specifically trained to recognize learn and generate images that accurately depict the distinctive characteristics of She ethnic group clothing. During the training process deep learning algorithms were employed to optimize the generated images ensuring high levels of detail fidelity and consistency in style. To evaluate the effectiveness of these models comparative analyses were conducted to assess the accuracy and alignment of the generated images with traditional She ethnic group clothing designs. The study introduced AIGC technology into the digital translation and innovative design of She ethnic group clothing by leveraging a specialized resource database for model training. This approach ensured the precise capture and creative transformation of traditional She ethnic group clothing elements. The in-depth analysis of the database samples enabled the high-precision reproduction of both style and detail in the generated images offering a feasible technological pathway for the modern design of ethnic clothing. Experimental results demonstrate that the images generated by the trained models effectively preserve the traditional style of She ethnic group clothing while incorporating modern aesthetic elementd. Compared to conventional manual design methods this approach significantly enhances design efficiency while outperforming in terms of style consistency and detail fidelity. The study's findings highlight the broad potential of AIGC technology in the innovative design of ethnic clothing validating the practicality and forward-thinking nature of AIGC methods based on custom model training in driving ethnic clothing innovation. The successful application of AIGC technology in the digital restoration and innovative design of She ethnic group clothing contributes new technological insights to the broader field of ethnic clothing innovation. As the field continues to evolve the fusion of advanced technology and traditional craftsmanship will play an increasingly important role in the ongoing effort to preserve and innovate ethnic clothing design. [ABSTRACT FROM AUTHOR]

Bladder cancer (BC) represents a wide spectrum of diseases, ranging from recurrent non-invasive tumors to advanced stages that require intensive treatments. BC accounts for an estimated 500,000 new cases and 200,000 deaths worldwide every year. Understanding the biology of BC has changed how this disease is diagnosed and treated. Bladder cancer is highly immunogenic, involving innate and adaptive components of the immune system. Although little is still known of how immune cells respond to BC, immunotherapy with bacillus Calmette–Guérin (BCG) remains the gold standard in high-risk non-muscle invasive BC. For muscle-invasive BC and metastatic stages, immune checkpoint inhibitors targeting CTLA-4, PD-1, and PD-L1 have emerged as potent therapies, enhancing immune surveillance and tumor cell elimination. This review aims to unravel the immune responses involving innate and adaptive immune cells in BC that will contribute to establishing new and promising therapeutic options, while reviewing the immunotherapies currently in use in bladder cancer. [ABSTRACT FROM AUTHOR]

This article analyses how and why the northwest borderland region of Pakistan has become one of the world’s most heavily militarised regions. Before 9/11, the area was a historical colonial frontier, experiencing significant militarism and violence during the Cold War. After the 9/11 attacks and the American and allied forces’ invasion and occupation of Afghanistan, however, the Pakistani military undertook a massive intervention and deployment in the region and established a chain of checkpoints aimed at filtering and disciplining the local population. Consequently, local inhabitants have endured severe treatment from the military and other coercive apparatuses. Using an ethnographic method, this article documents the daily experiences of the local people amidst pervasive militarisation. It contends that recent instances of state violence and militarisation cannot solely be attributed to 9/11 but are deeply rooted in the region’s historical treatment as a buffer zone during colonial times. In this context, Pakistan’s postcolonial state has heavily relied on its violent methods and securitised infrastructure to regulate both the region and its people. [ABSTRACT FROM AUTHOR]

Background: The regulation of cellular proliferation and genomic integrity is controlled by complex surveillance mechanisms known as cell cycle checkpoints. Disruptions in these checkpoints can lead to developmental defects and tumorigenesis. Methods: To better understand these mechanisms, computational modeling has been employed, resulting in a dataset of 414 mathematical models in the BioModels database. These models vary significantly in detail and simulated processes, necessitating a robust analytical approach. Results: In this study, we apply the chemical organization theory (COT) to these models to gain insights into their dynamic behaviors. COT, which handles both ordinary and partial differential equations (ODEs and PDEs), is utilized to analyze the compartmentalized structures of these models. COT's framework allows for the examination of persistent subsystems within these models, even when detailed kinetic parameters are unavailable. By computing and analyzing the lattice of organizations, we can compare and rank models based on their structural features and dynamic behavior. Conclusions: Our application of the COT reveals that models with compartmentalized organizations exhibit distinctive structural features that facilitate the understanding of phenomena such as periodicity in the cell cycle. This approach provides valuable insights into the dynamics of cell cycle control mechanisms, refining existing models and potentially guiding future research in this area. [ABSTRACT FROM AUTHOR]

Immunotherapy, a transformative approach in oncology, enhances the body's immune system to target and eliminate cancer cells. Key components such as immune checkpoint inhibitors, 'CAR-T cell therapy', monoclonal antibodies, and cancer vaccines play a crucial role. The study explores personalized treatment strategies and future directions, including epigenetic modulation and local immunotherapy. This study includes the details of factors that invade tumour progression and associated immunotherapies to prevent those. The future direction offers the new pathways and approaches such as epigenetic modulation to improve the process of immunotherapy. [ABSTRACT FROM AUTHOR]

With increasing levels of mobility, driven by political, economic, technological, and cultural factors, mobility regimes are established to facilitate and control both internal and cross-border travel. Still, the degree to which individuals are mobile is a function of multiple factors, including power, citizenship, ethnicity, income, education, culture, networks, and technology. We advance the concept of "Mobility Spaces" as a way to identify the implications of politically induced changes in mobility regimes for individuals. In particular, we show how politically induced shifts in such regimes affect the mobility options of different groups. Mobility spaces are defined as the area to which a person belonging to a certain group can possibly travel, in a regulated but unimpeded or in a partially impeded fashion. The restrictions limiting mobility spaces can be divided into three thematic hierarchies, domestic, international and for refugees. The mobility spaces implications of changes in mobility regimes resulting from political shifts are exemplified along the first two hierarchies for the Israeli-Palestinian and German-European cases. [ABSTRACT FROM AUTHOR]

The article analyzes the organizational and economic mechanism of customs services infrastructure development on the example of the Far Eastern Federal District. The purpose of the study is to assess spatial and territorial location of customs and near-customs infrastructure elements, as well as features of economic activity of infrastructure subjects such as customs authorities, customs representatives, customs carriers, duty-free stores owners, temporary storage warehouses owners, customs warehouses, free warehouses, andauthorized economic operators. The relevance of the conducted scientific research is conditioned by the need to apply a comprehensive approach to assessment of the Far East region infrastructure from the position of providing customs services throughout the foreign economic activity supply chain. The task of the study is to determine the potential of the Far Eastern Federal District infrastructure in the context of changing parameters of demand from the participants of foreign economic activity. The research concept is based on the service-oriented customs administration theory and general methodological approaches to regional economic research. The results obtained allow us to conclude that the demand for customs services exceeds the available supply of regional infrastructure. The problems of the regional mechanism functioning have been outlined: carrying and storage capacities deficit, low level of established checkpoints infrastructure involvement, their insufficient equipment, area and throughput capacity, as well as shortcomings in technological processes organization, including when making decisions on the spatial location of customs infrastructure facilities, investment resources allocation, and the lack of interconnected regulation.

Breast cancer (BC) is the most common malignancy among women and is considered a major global health challenge worldwide due to its high incidence and mortality rates. Treatment strategies for BC is wide-ranging and include surgery, radiotherapy, chemotherapy, targeted hormonal therapy and immunotherapy. Immunotherapy has gained popularity recently and is often integrated as a component of personalized cancer care because it aims to strengthen the immune system and enable it to recognize and eradicate transformed cells. It has fewer side-effects and lower toxicity than other treatment strategies, such as chemotherapy. Many natural products are being investigated for a wide range of therapeutic pharmacological properties, such as immune system modulation and activity against infection, auto-immune disease, and cancer. This review presents an overview of the major immune responserelated pathways in BC, followed by detailed explanation of how natural compounds can act as immunomodulatory agents against biomolecular targets. Research has been carried out on many forms of natural products, including extracts, isolated entities, synthetic derivatives, nanoparticles, and combinations of natural compounds. Findings have shown significant regulatory effects on immune cells and immune cytokines that lead to immunogenic cancer cell death, as well as upregulation of macrophages and CD+8 T cells, and increased natural killer cell and dendritic cell activity. Natural products have also been found to inhibit some immuno-suppressive cells such as Treg and myeloid-derived suppressor cells, and to decrease immunosuppressive factors such as TGF-b and IL-10. Also, some natural compounds have been found to target and hinder immune checkpoints such as PD-L1. [ABSTRACT FROM AUTHOR]

This article explores how bodily living and experiencing life as colonized subjects affects the perception of space and time. It argues that the Zionist settler-colonial trinity of control (checkpoints, ID cards, and permits) are not mere physical barriers of separation or restriction of movement and mobility. They are also a direct mechanism of colonial power that articulates how oppressive spaces are lived and consequently form the colonized perception of being-in-the-world. Based on two years of ethnographic study at Qalandia checkpoint between 2015 and 2017, the article adopts a phenomenological anthropological lens and focuses on two moments of bodily experiences related to passing the checkpoint: First, the bodily experience before reaching the checkpoint; and second, the bodily experience when crossing the checkpoint. [ABSTRACT FROM AUTHOR]

In this article, we explore how people in conflict-affected societies use language to navigate the affective constraints that political conflicts impose. Specifically, we consider the role of multilingualism in enabling sexual and romantic intimacy between Jewish and Palestinian Israelis in Israel/Palestine. Our data are drawn from a close examination of the speech of Fadi Daeem, one of the protagonists in the 2015 documentary Oriented. Building on studies of (in)securitization and everyday bordering, we show how the ongoing armed conflict between Israel and Palestine serves to instantiate a regime of affective checkpoints, a space in which sexual and romantic relations between Jewish Israelis and Palestinians are discursively blocked. We describe how Fadi and his friends use strategic instances of code-switching between Arabic, Hebrew, and English to navigate this ideologically fraught terrain. Our primary goal is to demonstrate how multilingualism can be employed as a resource for managing affect and desire in a conflict-ridden context like Israel/Palestine. In doing so, we further highlight how the intimate domain of romantic desire is inevitably situated within a broader matrix of power and constraint. [ABSTRACT FROM AUTHOR]

This editorial titled "Molecular architecture and dynamics of meiotic chromosomes" explores the unique processes involved in meiosis, a type of cell division essential for sexual reproduction in animals, plants, and fungi. It discusses the conservation of meiosis throughout evolution and presents selected research articles on the composition, architecture, function, and regulation of meiotic chromosomes in different species. The document covers topics such as the role of the chromosome axis, pairing and chromosome dynamics, regulation of meiotic progression, and the importance of checkpoints and protein phosphorylation. It also discusses the significance of regulators, such as the polo-like kinase PLK1, in ensuring the accurate transmission of genetic information during meiosis. The document highlights the functions of the nuclear envelope and nuclear pore complexes in meiosis, including their roles in chromosome movement and control of meiotic progression. The authors emphasize the need for further research to fully understand the complex processes of meiosis and its potential applications in agriculture and healthcare. [Extracted from the article]

Breast cancer (BC) is the most common malignancy among women and is considered a major global health challenge worldwide due to its high incidence and mortality rates. Treatment strategies for BC is wide-ranging and include surgery, radiotherapy, chemotherapy, targeted hormonal therapy and immunotherapy. Immunotherapy has gained popularity recently and is often integrated as a component of personalized cancer care because it aims to strengthen the immune system and enable it to recognize and eradicate transformed cells. It has fewer side-effects and lower toxicity than other treatment strategies, such as chemotherapy. Many natural products are being investigated for a wide range of therapeutic pharmacological properties, such as immune system modulation and activity against infection, auto-immune disease, and cancer. This review presents an overview of the major immune response-related pathways in BC, followed by detailed explanation of how natural compounds can act as immunomodulatory agents against biomolecular targets. Research has been carried out on many forms of natural products, including extracts, isolated entities, synthetic derivatives, nanoparticles, and combinations of natural compounds. Findings have shown significant regulatory effects on immune cells and immune cytokines that lead to immunogenic cancer cell death, as well as upregulation of macrophages and CD+8 T cells, and increased natural killer cell and dendritic cell activity. Natural products have also been found to inhibit some immuno-suppressive cells such as Treg and myeloid-derived suppressor cells, and to decrease immunosuppressive factors such as TGF-β and IL-10. Also, some natural compounds have been found to target and hinder immune checkpoints such as PD-L1.

Background: The regulation of cellular proliferation and genomic integrity is controlled by complex surveillance mechanisms known as cell cycle checkpoints. Disruptions in these checkpoints can lead to developmental defects and tumorigenesis. Methods: To better understand these mechanisms, computational modeling has been employed, resulting in a dataset of 414 mathematical models in the BioModels database. These models vary significantly in detail and simulated processes, necessitating a robust analytical approach. Results: In this study, we apply the chemical organization theory (COT) to these models to gain insights into their dynamic behaviors. COT, which handles both ordinary and partial differential equations (ODEs and PDEs), is utilized to analyze the compartmentalized structures of these models. COT’s framework allows for the examination of persistent subsystems within these models, even when detailed kinetic parameters are unavailable. By computing and analyzing the lattice of organizations, we can compare and rank models based on their structural features and dynamic behavior. Conclusions: Our application of the COT reveals that models with compartmentalized organizations exhibit distinctive structural features that facilitate the understanding of phenomena such as periodicity in the cell cycle. This approach provides valuable insights into the dynamics of cell cycle control mechanisms, refining existing models and potentially guiding future research in this area.

We have recently reported that in G2-phase cells (but not S-phase cells) sustaining low loads of DNA double-strand break (DSBs), ATM and ATR regulate the G2-checkpoint epistatically, with ATR at the output-node, interfacing with the cell cycle through Chk1. However, although inhibition of ATR nearly completely abrogated the checkpoint, inhibition of Chk1 using UCN-01 generated only partial responses. This suggested that additional kinases downstream of ATR were involved in the transmission of the signal to the cell cycle engine. Additionally, the broad spectrum of kinases inhibited by UCN-01 pointed to uncertainties in the interpretation that warranted further investigations. Here, we show that more specific Chk1 inhibitors exert an even weaker effect on G2-checkpoint, as compared to ATR inhibitors and UCN-01, and identify the MAPK p38α and its downstream target MK2 as checkpoint effectors operating as backup to Chk1. These observations further expand the spectrum of p38/MK2 signaling to G2-checkpoint activation, extend similar studies in cells exposed to other DNA damaging agents and consolidate a role of p38/MK2 as a backup kinase module, adding to similar backup functions exerted in p53 deficient cells. The results extend the spectrum of actionable strategies and targets in current efforts to enhance the radiosensitivity in tumor cells. [ABSTRACT FROM AUTHOR]

Covalent modifications of chromatin regulate genomic structure and accessibility in diverse biological processes such as transcriptional regulation, cell cycle progression, and DNA damage repair. Many histone modifications have been characterized, yet understanding the interactions between these and their combinatorial effects remains an active area of investigation, including dissecting functional interactions between enzymes mediating these modifications. In budding yeast, the histone acetyltransferase Gcn5 interacts with Rts1, a regulatory subunit of protein phosphatase 2A (PP2A). Implicated in the interaction is the potential for the dynamic phosphorylation of conserved residues on histone H2B and the Cse4 centromere-specific histone H3 variant. To probe these dynamics, we sought to identify kinases which contribute to the phosphorylated state. In a directed screen beginning with in silico analysis of the 127 members of yeast kinome, we have now identified 16 kinases with genetic interactions with GCN5 and specifically found distinct roles for the Hog1 stress-activated protein kinase. Deletion of HOG1 (hog1Δ) rescues gcn5Δ sensitivity to the microtubule poison nocodazole and the lethality of the gcn5Δ rts1Δ double mutant. The Hog1-Gcn5 interaction requires the conserved H2B-T91 residue, which is phosphorylated in vertebrate species. Furthermore, deletion of HOG1 decreases aneuploidy and apoptotic populations in gcn5Δ cells. Together, these results introduce Hog1 as a kinase that functionally opposes Gcn5 and Rts1 in the context of the spindle assembly checkpoint and suggest further kinases may also influence GCN5's functions. [ABSTRACT FROM AUTHOR]

Meiotic cells introduce numerous programmed DNA double-strand breaks (DSBs) into their genome to stimulate crossover recombination. DSB numbers must be high enough to ensure each homologous chromosome pair receives the obligate crossover required for accurate meiotic chromosome segregation. However, every DSB also increases the risk of aberrant or incomplete DNA repair, and thus genome instability. To mitigate these risks, meiotic cells have evolved an intricate network of controls that modulates the timing, levels, and genomic location of meiotic DSBs. This Review summarizes our current understanding of these controls with a particular focus on the mechanisms that prevent meiotic DSB formation at the wrong time or place, thereby guarding the genome from potentially catastrophic meiotic errors., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Between 2003–2017, multiple state and non-state factions fought for control of Baghdad, Iraq. Government-sanctioned armed groups and illegal militias each constructed and appropriated defensive architecture for their own purposes. This article argues that licit and illicit armed groups co-produced Baghdad’s security infrastructures, creating increasingly homogeneous neighborhoods. Within the walls and behind checkpoints, residents’ restriction of movement and vision resulted in an ‘antiopticon’ in which they faced and negotiated a changing environment of new places and non-places. Through an extensive literature review from the fields of anthropology, urban studies, and conflict studies, this paper explores the tangible role that illicit armed groups played in shaping Baghdad’s urban geography and its residents’ sense of place.

Cancer immunotherapy moderates the immune system's ability to fight cancer. Due to its extreme complexity, scientists are working to put together all the puzzle pieces to get a clearer picture of the immune system. Shreds of available evidence show the connection between cancer and the immune system. Immune responses to tumors and lymphoid malignancies are influenced by B cells, γδT cells, NK cells, and dendritic cells (DCs). Cancer immunotherapy, which encompasses adoptive cancer therapy, monoclonal antibodies (mAbs), immune checkpoint therapy, and CART cells, has revolutionized contemporary cancer treatment. This article reviews recent developments in immune cell regulation and cancer immunotherapy. Various options are available to treat many diseases, particularly cancer, due to the progress in various immunotherapies, such as monoclonal antibodies, recombinant proteins, vaccinations (both preventative and curative), cellular immunotherapies, and cytokines. [ABSTRACT FROM AUTHOR]

Between 2003-2017, multiple state and non-state factions fought for control of Baghdad, Iraq. Government-sanctioned armed groups and illegal militias each constructed and appropriated defensive architecture for their own purposes. This article argues that licit and illicit armed groups co-produced Baghdad's security infrastructures, creating increasingly homogeneous neighborhoods. Within the walls and behind checkpoints, residents' restriction of movement and vision resulted in an 'antiopticon' in which they faced and negotiated a changing environment of new places and non-places. Through an extensive literature review from the fields of anthropology, urban studies, and conflict studies, this paper explores the tangible role that illicit armed groups played in shaping Baghdad's urban geography and its residents' sense of place. [ABSTRACT FROM AUTHOR]

Cellular checkpoints prevent damage and mutation accumulation in tissue cells. DNA repair is one mechanism that can be triggered by checkpoints and involves temporary cell cycle arrest and thus delayed reproduction. Repair-deficient cells avoid this delay, which has been argued to lead to a selective advantage in the presence of frequent damage. We investigate this hypothesis with stochastic modeling, using mathematical analysis and agent-based computations. We first model competition between two cell types: a cell population that enters temporary cell cycle arrest, corresponding to repair (referred to as arresting cells), and one that does not enter arrest (referred to as nonarresting cells). Although nonarresting cells are predicted to grow with a faster rate than arresting cells in isolation, this does not translate into a selective advantage in the model. Interestingly, the evolutionary properties of the nonarresting cells depend on the measure (or observable) of interest. When examining the average populations sizes in competition simulations, nonarresting and arresting cells display neutral dynamics. The fixation probability of nonarresting mutants, however, is lower than predicted for a neutral scenario, suggesting a selective disadvantage in this setting. For nonarresting cells to gain a selective advantage, additional mechanisms must be invoked in the model, such as small, repeated phases of tissue damage, each resulting in a brief period of regenerative growth. The same properties are observed in a more complex model where it is explicitly assumed that repair and temporary cell cycle arrest are dependent on the cell having sustained DNA damage, the rate of which can be varied. We conclude that repair-deficient cells are not automatically advantageous in the presence of frequent DNA damage and that mechanisms beyond avoidance of cell cycle delay must be invoked to explain their emergence.

Iraq is home to a patchwork of competing sovereignties with their own security actors, all of which routinely use checkpoints in the provision of 'security'. However, as this article demonstrates, checkpoints predominantly function to assert authority over space. Utilising 262 interviews with those forced to move through checkpoints in Nineveh, Iraq, and through the development of an analytical framework that focuses on the 'theft of time' and the 'stolen dignity', this article examines the everyday strain that checkpoints exert on people's lives. It asks what the control of space by the multiplicity of competing 'sovereignties' means for those who must live in and in between these spaces. In doing so the article demonstrates how the impacts of creating borders reverberate way beyond the checkpoint itself, the inequalities it creates and reproduces, and the varied types of loss it fashions. [ABSTRACT FROM AUTHOR]

The word "tumor" is a Greek term that refers to a swelling or a lump. In modern medical terms, a tumor is usually an abnormal mass of cells and tissues which grows due to the abnormal division of cells. The unnatural division of cells occurs due to the cancerous nature of these cells, which no longer obey standard checkpoints that prevent healthy or non-cancerous cells from uncontrolled cell divisions. Tumors may be circumscribed or diffuse depending on whether they remain localized to a part of the brain or spread to other parts aggressively by metastasis; in 2016, WHO has classified tumors of the brain or central nervous system by taking into account the latest molecular genetic data along with classic histopathological features characteristic of each kind of tumor. The new classification system makes diagnosis more precise, but a better prognosis analysis is now possible since genotype is far more determinative and accurate than histological phenotype. Modern technologies like high throughput gene sequencing, CRISPR-Cas9 gene editing, and personalized medicine approaches have improved the prognosis of brain tumor patients. They have also revolutionized our understanding of the biology of brain tumors and how they are now being treated. In this review, we will discuss the latest knowledge about the biology of brain tumors and how modern technologies are helping to understand the molecular basis of these pathologies and develop better treatment options to improve patient survival. [ABSTRACT FROM AUTHOR]

The development of immunotherapeutic approaches for the treatment of melanoma requires a better understanding of immunoescape mechanisms of tumor cells and how they interact with other tumor-resident cell types. Here, we evaluated how the conditioned media of resting (rCM) and immune-activated PBMCs (iCM) influence the ability of a metastatic melanoma cell line (MeWo) to control T-cells function. MeWo cells were expanded in RPMI, rCM, or iCM and the secretome generated after cell expansion was identified as MeSec (RPMI), niSec (non-inflammatory), or iSec (inflammatory secretome), respectively. Then, the immunomodulatory potential of such secretomes was tested in PHA-activated PBMCs. iCM induced higher levels of IFN-γ and IL-10 in treated melanoma cells compared to rCM, as well as higher IDO and PD-L1 expression. The iSec was able to inhibit T-cell activation and proliferation. Interestingly, PBMCs treated with iSec presented a reduced expression of the regulators of Th1 and Th2 responses T-BET and GATA-3 , as well as low expression of IFN-γ , and co-stimulatory molecules TIM-3 and LAG-3. Importantly, our findings show that melanoma may benefit from an inflammatory microenvironment to enhance its ability to control the T-cell response. Interestingly, such an immunomodulatory effect involves the inhibition of the checkpoint molecules LAG-3 and TIM-3 , which are currently investigated as important therapeutic targets for melanoma treatment. Further studies are needed to better understand how checkpoint molecules are modulated by paracrine and cell contact-dependent interaction between melanoma and immune cells. Such advances are fundamental for the development of new therapeutic approaches focused on melanoma immunotherapy. [ABSTRACT FROM AUTHOR]

Many mathematics students require support for learning challenges, such as those invoked by mathematics anxiety. Support for these learning challenges is imparted through personal interactions between the student and the instructor, support staff or their peers. The online delivery of mathematics classes and support meetings reduced the quality of the interactions compared to face-to-face interactions. This article presents an alternative approach used to support students with learning challenges in a virtual learning environment. The approach reported was used in a four week online preparatory mathematics subject. Most of the students were mature age, some years out of formal mathematics education, and low in confidence. In preparing the modules the nature of the subject and the cohort was considered and additional content called Checkpoints was added. The Checkpoint pages were designed to alleviate the learning challenges the students faced by including signposting, supporting positive dispositions, providing alternative learning strategies, and sharing assessment strategies. Feedback showed students engaged with the Checkpoints and found them helpful, leading the students to reflect on their learning. The checkpoints also 'chunked' the math content, resulting in a 'nice break', and provided students with reassurance they were on-track. [ABSTRACT FROM AUTHOR]

Sepsis is a life-threatening syndrome with a high incidence and a weighty economic burden. The cytokines storm in the early stage and the state of immunosuppression in the late stage contribute to the mortality of sepsis. Immune checkpoints expressed on lymphocytes and APCs, including CD28, CTLA-4, CD80, CD86, PD-1 and PD-L1, CD40 and CD40L, OX40 and OX40L, 4-1BB and 4-1BBL, BTLA, TIM family, play significant roles in the pathogenesis of sepsis through regulating the immune disorder. The specific therapies targeting immune checkpoints exhibit great potentials in the animal and preclinical studies, and further clinical trials are planning to implement. Here, we review the current literature on the roles played by immune checkpoints in the pathogenesis and treatment of sepsis. We hope to provide further insights into this novel immunomodulatory strategy. [ABSTRACT FROM AUTHOR]

The development of immunotherapeutic approaches for the treatment of melanoma requires a better understanding of immunoescape mechanisms of tumor cells and how they interact with other tumor-resident cell types. Here, we evaluated how the conditioned media of resting (rCM) and immune-activated PBMCs (iCM) influence the ability of a metastatic melanoma cell line (MeWo) to control T-cells function. MeWo cells were expanded in RPMI, rCM, or iCM and the secretome generated after cell expansion was identified as MeSec (RPMI), niSec (non-inflammatory), or iSec (inflammatory secretome), respectively. Then, the immunomodulatory potential of such secretomes was tested in PHA-activated PBMCs. iCM induced higher levels of IFN-γ and IL-10 in treated melanoma cells compared to rCM, as well as higher IDO and PD-L1 expression. The iSec was able to inhibit T-cell activation and proliferation. Interestingly, PBMCs treated with iSec presented a reduced expression of the regulators of Th1 and Th2 responses T-BET and GATA-3, as well as low expression of IFN-γ, and co-stimulatory molecules TIM-3 and LAG-3. Importantly, our findings show that melanoma may benefit from an inflammatory microenvironment to enhance its ability to control the T-cell response. Interestingly, such an immunomodulatory effect involves the inhibition of the checkpoint molecules LAG-3 and TIM-3, which are currently investigated as important therapeutic targets for melanoma treatment. Further studies are needed to better understand how checkpoint molecules are modulated by paracrine and cell contact-dependent interaction between melanoma and immune cells. Such advances are fundamental for the development of new therapeutic approaches focused on melanoma immunotherapy.

The cell division cycle is a fundamental physiological process displaying a great degree of plasticity during the course of multicellular development. This plasticity is evident in the transition from rapid and stringently-timed divisions of the early embryo to subsequent size-controlled mitotic cycles. Later in development, cells may pause and restart proliferation in response to myriads of internal or external signals, or permanently exit the cell cycle following terminal differentiation or senescence. Beyond this, cells can undergo modified cell division variants, such as endoreplication, which increases their ploidy, or meiosis, which reduces their ploidy. This wealth of behaviours has led to numerous conceptual analogies intended as frameworks for understanding the proliferative program. Here, we aim to unify these mechanisms under one dynamical paradigm. To this end, we take a control theoretical approach to frame the cell cycle as a pair of arrestable and mutually-inhibiting, doubly amplified, negative feedback oscillators controlling chromosome replication and segregation events, respectively. Under appropriate conditions, this framework can reproduce fixed-period oscillations, checkpoint arrests of variable duration, and endocycles. Subsequently, we use phase plane and bifurcation analysis to explain the dynamical basis of these properties. Then, using a physiologically realistic, biochemical model, we show that the very same regulatory structure underpins the diverse functions of the cell cycle control network. We conclude that Newton's cradle may be a suitable mechanical analogy of how the cell cycle is regulated., Competing Interests: Declaration of competing interest The authors declare no competing or financial interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Patients treated with immunotherapy might need surgical procedures in addition to the medical treatment. The main indications are cytoreductive nephrectomy, cystectomy (as part of clinical trials) and metastasis removal in some oligometastatic patients. This study aims to assess the feasibility of surgery for patients treated by immunotherapy and describes the histological modifications found in the pathological analysis., Material and Methods: We conducted a retrospective, monocentric study. We included all patients operated for a urologic cancer and previously treated with systemic immunotherapy between February 2018 and June 2022. We compared this population with a control group of patients treated with surgery without having previous immunotherapy. Patients were compared according to the cancer type, age and sex. We compared perioperative complications. We performed an analysis for evaluation of the peri-tumoral inflammatory infiltration., Results: We included 50 patients in this study. The two groups were comparable in age (63.7 vs. 63.3years old, P=0.95) and sex (4 and 6 women in the first and second group). The peroperatory complication rate was comparable (20% vs. 16%, P=1). The mean bleeding volume was comparable (664 vs. 629mL; P=0.89). The postoperative complication rate (48% vs. 56%; P=0.78) and their grade (Clavien III-IV 8% vs. 24%; P=0.24) were comparable. The anatomopathological analysis described the same rate and intensity of peri-tumoral inflammatory infiltrate (96% vs. 96%; P=1)., Conclusions: Preoperative immunotherapy does not appear to be associated with increased surgical difficulty and perioperative complications. Blind histological analysis of the surgical specimens did not reveal any specific features related to pre operative immunotherapy., Level of Evidence: Grade 3 HAS., (Copyright © 2024 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

Sepsis is a syndrome characterized by life-threatening organ dysfunction caused by the dysregulated host response to an infection. Sepsis, especially septic shock and multiple organ dysfunction is a medical emergency associated with high morbidity, high mortality, and prolonged after-effects. Over the past 20 years, regulatory T cells (Tregs) have been a key topic of focus in all stages of sepsis research. Tregs play a controversial role in sepsis based on their heterogeneous characteristics, complex organ/tissue-specific patterns in the host, the multi-dimensional heterogeneous syndrome of sepsis, the different types of pathogenic microbiology, and even different types of laboratory research models and clinical research methods. In the context of sepsis, Tregs may be considered both angels and demons. We propose that the symptoms and signs of sepsis can be attenuated by regulating Tregs. This review summarizes the controversial roles and Treg checkpoints in sepsis.

Sepsis is a syndrome characterized by life-threatening organ dysfunction caused by the dysregulated host response to an infection. Sepsis, especially septic shock and multiple organ dysfunction is a medical emergency associated with high morbidity, high mortality, and prolonged after-effects. Over the past 20 years, regulatory T cells (Tregs) have been a key topic of focus in all stages of sepsis research. Tregs play a controversial role in sepsis based on their heterogeneous characteristics, complex organ/tissue-specific patterns in the host, the multi-dimensional heterogeneous syndrome of sepsis, the different types of pathogenic microbiology, and even different types of laboratory research models and clinical research methods. In the context of sepsis, Tregs may be considered both angels and demons. We propose that the symptoms and signs of sepsis can be attenuated by regulating Tregs. This review summarizes the controversial roles and Treg checkpoints in sepsis. [ABSTRACT FROM AUTHOR]

In recent years, cloud is being widely used to host numerous distributed applications. The expanding usage of cloud has introduced greater sensitivity in the environment. Therefore, most of the applications require that an effective fault tolerant mechanism must be in place. A fault tolerant mechanism involves detection as well as recovery from failures; traditionally checkpointing has been used to serve the purpose. The conventional checkpointing methods have also been tried in cloud e.g., periodic checkpointing and application based checkpointing; however, the periodic checkpointing is time inefficient and the application based checkpointing is space inefficient. Secondly, the above methods have been implemented using synchronous approach, which is inherently message inefficient, less scalable and has high synchronization latency. Furthermore, the asynchronous approaches are practically not viable owing to their inability to detect failures. In addition, the cloud entails massive scalability, thus we have proposed a quasi-synchronous checkpointing algorithm for cloud based distributed applications that exhibits better space efficiency while keeping latency under strict control. Our claims have been substantiated with static analysis and suitable simulation experiments. [ABSTRACT FROM AUTHOR]

Acute myeloid leukemia (AML) patients rarely have long first remissions (LFRs; >5 y) after standard-of-care chemotherapy, unless classified as favorable risk at presentation. Identification of the mechanisms responsible for long vs. more typical, standard remissions may help to define prognostic determinants for chemotherapy responses. Using exome sequencing, RNA-sequencing, and functional immunologic studies, we characterized 28 normal karyotype (NK)-AML patients with >5 y first remissions after chemotherapy (LFRs) and compared them to a well-matched group of 31 NK-AML patients who relapsed within 2 y (standard first remissions [SFRs]). Our combined analyses indicated that genetic-risk profiling at presentation (as defined by European LeukemiaNet [ELN] 2017 criteria) was not sufficient to explain the outcomes of many SFR cases. Single-cell RNA-sequencing studies of 15 AML samples showed that SFR AML cells differentially expressed many genes associated with immune suppression. The bone marrow of SFR cases had significantly fewer CD4+ Th1 cells; these T cells expressed an exhaustion signature and were resistant to activation by T cell receptor stimulation in the presence of autologous AML cells. T cell activation could be restored by removing the AML cells or blocking the inhibitory major histocompatibility complex class II receptor, LAG3. Most LFR cases did not display these features, suggesting that their AML cells were not as immunosuppressive. These findings were confirmed and extended in an independent set of 50 AML cases representing all ELN 2017 risk groups. AML cell-mediated suppression of CD4+ T cell activation at presentation is strongly associated with unfavorable outcomes in AML patients treated with standard chemotherapy. [ABSTRACT FROM AUTHOR]

This article is published as part of the Geografiska Annaler: Series B, Human Geography special issue 'Palestinian Futures Anticipation, Imagination, Embodiments', edited by Mikko Joronen, Helga Tawil-Souri, Merav Amir & Mark Griffiths. The almost 100 Israeli checkpoints that are located inside the West Bank and on its 'border' with Israel play a particularly important role in the architecture of occupation. They represent key political technologies that are used to monitor, discipline and/or selectively limit the mobility of Palestinians. In this paper, I analyse the ways in which the design of the newly relaunched Checkpoint 300 in Bethlehem represents a certain specific 'checkpoint future', materialized in the continued 'evolution' of Checkpoint 300, its machines and 'façade of legitimacy': a future in which the Israeli military regime controlling the Occupied Palestinian Territories (OPT) is kept in place and the checkpoints and their inherent violence are increasingly normalized. Furthermore, I argue that this 'checkpoint future' does not lead to a less violent or arbitrary checkpoint regime. This remaining presence of violence should not be framed as a failure, instead, the continued presence of violence, analysed here as experienced and expressed in the arbitrary functioning of the checkpoint machines, as well as the 'legitimised façade' of Checkpoint 300 are intrinsically bound and an expression of the same violent future: a future with an enduring Israeli military regime in the Occupied Palestinian Territories. [ABSTRACT FROM AUTHOR]

INTRODUCTION: This research project is associated with a small rural community utilising the Te Ao Māori (Ngā ti Manawa) understanding of Rā hui, as a means of decreasing the possibility of negative impacts for their mostly Māori population, during the Covid-19 pandemic that was experienced in March 2020 in Aotearoa New Zealand. Rāhui is a conservation measure shrouded in tapu designed to limit, restrict or prevent access to the natural environment. For example, Te Wao Tapu nui a Tāne protecting in the process the mauri of our rivers, lakes, streams following a mishap or misfortune such as a drowning. Equally as important, Rāhui was used as a proactive means of conservation. METHOD: Using mixed methods, this study highlights both positive and challenging experiences in the statistical and thematic analysis that may inform future public health planning for the inevitable and ongoing effects of pandemic responses in Aotearoa New Zealand which are potentially transportable beyond Aotearoa New Zealand. IMPLICATIONS: This research identified how Ngāti Manawa of Murupara, utilised Rāhui as a mechanism of resilience in order to keep local residents thriving and healthy during and after the Covid-19 pandemic lockdown by setting up checkpoints on the borders of their rohe, and restricting the vehicle and human traffic into Murupara. Support for the Rāhui was significant from five hapūleaders and from the community survey illuminating a sense of safety that the checkpoints offered to a vulnerable and mostly Māori rural community. [ABSTRACT FROM AUTHOR]