A document by Ezgi Karaca. Click on the document to view its contents.

Adenosine (Ado), mainly produced by the hydrolysis of ATP, exhibits significantly elevated levels in the tumor microenvironment (TME) compared to normal tissues. Upon binding to adenosine receptors (AdoRs), Ado initiates downstream signaling pathways that suppress tumor antigen presentation and immune cell activation, thereby inhibiting tumor adaptive immunity. Ado downregulates major histocompatibility complex II (MHC II) and co-stimulatory factors expression on DCs and macrophages, thereby inhibiting antigen presentation to T cells. Ado inhibits the binding of the T cell receptor (TCR) to its ligand and transmembrane signal transduction on T cells, thus suppressing anti-tumor cytokines secretion and inhibiting T cell activation. Ado also inhibits the secretion of chemokines and the KCa3.1 channel, thereby suppressing the trafficking and infiltration of effector T cells into the tumor site. Moreover, Ado inhibits the cytotoxicity of T cells against tumor cells by promoting the secretion of immune-suppressive cytokines, increasing the expression of immune checkpoint proteins, and enhancing the activity of immune-suppressive cells. Due to the inhibitory effects of Ado on tumor adaptive immunity, reducing Ado production in the TME can exert significant anti-tumor immune effects and enhance the efficacy of other immunotherapies. Various inhibitors blocking Ado generation or AdoRs are now under preclinical or clinical development. Therefore, this article will summarize and analyze the inhibitory effects and molecular mechanisms of Ado on tumor adaptive immunity, as well as provide an overview of the latest advancements in targeting Ado pathways in anti-tumor immune responses.

(Micro)plastics are ubiquitous in our daily lives and are becoming a global emerging pollutant with significant threat to ecosystem sustainability. Within the field of soil erosion control engineering (ECE) in China, a wide range of plastic products, such as plastic mesh, planting bags, and plastic geocells, are extensively employed to stable the topsoil and facilitate the restoration of disturbed land. In this paper, we demonstrate the wide distribution of (micro)plastics in ECE across varied landscapes in China, highlighting their relatively high degradation rate induced by ultraviolet irradiation and mechanical disturbance. Furthermore, (micro)plastics in ECE exhibit a propensity for transport through soil erosion processes, thereby heightening the pollution risk to aquatic ecosystems. While the presence of (micro)plastics in ECE raises significant environmental concerns, there could be straightforward and easily implementable preventive strategies. These strategies include meticulous managing plastic usage during the design and completion phases of ECE, replacing plastic materials with biodegradable alternatives, and cleaning and retrieving temporary work materials.

Wildlife populations can be unmarked, meaning individuals lack visually distinguishing features for identification; populations may also exhibit non-independent movements, meaning individuals move together. For either unmarked or non-independent individuals, models based on spatial capture-recapture (SCR) approaches estimate abundance, density, and other population parameters critical for monitoring, management, and conservation. However, when individuals are both unmarked and non-independent, few model options exist. One approach has been to apply unmarked models and not address the non-independence despite unquantified impacts of overdispersion on bias, precision, and the ability to make robust ecological inferences. We conducted a simulation study to quantify the impact of non-independence on the performance of spatial count (SC) and spatial partial identity models (SPIM), two SCR-based unmarked modeling approaches, and used the performance of fully marked and independent SCR as a reference. We varied the levels of non-independence (aggregation and cohesion), detection probability, and the number of partial identity covariates used to resolve identities in SPIM estimation. We expected estimates of abundance and sigma (the spatial scale of individual movement) to be increasingly biased and less precise as aggregation and cohesion increased. Results showed that models indeed became less robust to increasing non-independence, especially for abundance, but importantly suggested that only SPIM could be reliably applied under low levels of cohesion when sufficient partial identity covariates are available. SC yielded consistently biased estimates with inflated precision that could not be corrected to nominal levels of coverage. SCR was the most robust across all combinations of aggregation and cohesion, as expected. We therefore advise against the use of SC models for estimating population parameters when individuals are known to be non-independent, caution that SPIM may be used under narrow ecological conditions, and encourage continued investigations into sampling design and methods development for populations of unmarked and non-independent individuals.

This study focuses on electron-selective passivating contacts for crystalline silicon (c-Si) solar cells where an interlayer is used to provide a low contact resistivity between the c-Si substrate and the metal electrode. These electron contact interlayers are used in combination with other passivating interlayers (e.g., a-Si:H, TiO2, and Nb2O5) to improve surface passivation whilst still permitting contact resistivities suitable for high efficiency solar cells. We show that a wide variety of thermally evaporated materials, most of which have ionic character, enable an Ohmic contact between n-type c-Si and Al. From this pool of compounds, we observed that CsBr has especially promising behavior because of its excellent performance and thermal stability when combined with thin passivating layers. With different test structures, we were able to demonstrate low contact resistance using TiO2/CsBr, Nb2O5/CsBr and a-Si:H/CsBr stacks on n-type c-Si. The quality of the provided surface passivation depended on the stack but we achieved the best overall passivation stability with TiO2/CsBr. Finally, we were able to demonstrate an efficiency >20% on a laboratory-scale solar cell that implements the TiO2/CsBr/Al stack as full-area rear side electron selective contact.

Increased deployment of solar PV enables the transition to decarbonized energy systems, capable of tempering the dire consequences of global warming. Even though backsheets are very important regarding lifetime energy yield of the PV module, the environmental impacts of their production, use and end-of-life (EoL) processing are largely neglected. As part of a recently finalized Dutch national project EXTENSIBLE (Energy yield assessment of neXT gENeration and SustaInaBLE backsheets) the environmental impacts for 7 different polymeric backsheets have been evaluated via a life cycle assessment (LCA). The selected backsheets include 3 traditional polyethylene terephthalate (PET) - based backsheets with a fluorine containing outer layer (two white pigmented and one fully transparent). The other 4 backsheets are novel high-performance polyolefin (PO) -based backsheets, manufactured by Endurans Solar ™, also including one transparent version. From results of the LCA it is concluded that in comparison with PET-based backsheets and fluoropolymer containing backsheets, PO-based backsheets perform best in terms of energy yield, reliability and environmental impacts. The production of fluoropolymer- and PET-based backsheets cause substantial environmental impacts, especially regarding climate change and ozone depletion. This conclusion is corroborated by recent literature data. Regarding the EoL phase, it was shown from a theoretical assessment that pyrolysis of the spent backsheets potentially leads to much lower GWP when compared to incineration, especially for the PO-based backsheets. Incineration of the shredded and solid backsheet material causes direct emissions of CO 2 with a limited heat recovery potential only. Deploying pyrolysis for spent PO-based backsheets significantly improves their life-time GWP per kWh produced. Pyrolysis offers the possibility to recover a large part of the polyolefin as an usable pyrolysis oil that might serve as feedstock for chemicals or as transportable liquid fuel for the generation of process heat in recovery boilers, thereby avoiding the use of new fossil resources. EoL pyrolysis (or incineration) of fluoropolymer-based backsheets is problematic due to the presence of fluorinated hydrocarbons, leading to corrosive and/or toxic products.

A document by Badal Karki. Click on the document to view its contents.

A quarter century after the 1998 El Niño, it is still difficult to predict how individual reefs will respond to recurring disturbances. Reports differ on the relative importance of anthropogenic influences, local geography and bleaching recurrence in determining resistance and recovery. It is assumed that coral traits largely determine winners and losers, based on bleaching susceptibility, recruitment, survival and growth. Whether this translates to the long-term fates of corals on reefs is still debated. We tracked multi-decadal coral compositional changes in reefs across the densely populated Lakshadweep Archipelago to explore how global bleaching events and local geographical factors (depth and wave exposure) influenced responses to repeated mass bleaching. Coral resistance increased with recurrent bleaching, uninfluenced by local geography. However, wave exposure regimes positively influenced recovery rates, given sufficient time between mortality events (>7 years). The overall trajectory though, was of protracted decline interspersed with periods of halting recovery, with many losers, and few resistant genera that lose less. Based on these responses, we identified six community clusters that describe contrasting long-term responses to local and global factors. Interestingly, genera with different functional traits cluster together, sharing similar fates, as a result of complex interactions between bleaching susceptibility, local geography and inter-bleaching intervals. These clusters provide a clear site-specific predictive framework of long-term community change, indicating that geography, community and time largely determine local responses to climate disturbances.

Title: The Effect of Disorders of Sleep on Cardiac Health, Mechanisms, Diagnoses, and Treatment Options.

Reply to: Two Ripples in a Pond: The Subtleties of Mapping Observations in Localizing

Angiotensin converting enzyme-2 (ACE2), a key component in renin-angiotensin system (RAS) has been identified as the functional receptor for mediating the entry into the cell of SARS-CoV-2. The correlation between anti-ACE2 antibodies and COVID-19 outcome is less well-defined. Herein, serum sample were collected from 134 inpatients, 22 outpatients, 40 convalesces and 12 healthy individuals, with real-time PCR-confirmed SARS-COV-2 infections. The anti-ACE2 antibodies were tested by ELASA and anti-SARS-COV-2 antibodies were analyzed by chemiluminescent immunoassay.We found that patients with COVID-19 show a high prevalence of autoantibodies against ACE2 and exhibit marked increases level compared to healthy control. The highest level of anti-ACE2 was observed in death, male, and longer time of admission group. Thus, significant negative association between serum anti-ACE2 antibodies levels and anti-SARS-COV-2 in different severity group was observed. We conclude that patients with a history of SARS-CoV-2 infection had a high prevalence of Anti-ACE2 antibodies. Its negative correlation with anti-SARS-COV-2 antibodies may lead to pro-inflammatory responses and weaken the protective power of humoral immunity by enhancing RAS pro-inflammatory axis.

Maxillary cast partial denture and mandibular implant supported ceramometal prosthesis with a split-framework to compensate for mandibular flexure: A case report

Background and Purpose The gut hormone glucose-dependent insulinotropic polypeptide (GIP) signals via the GIP receptor (GIPR) resulting in postprandial processes such as potentiation of glucose-stimulated insulin secretion. Translation of results from rodent to human studies has, however, been challenged by contradictive therapeutic effects of GIPR-targeting compounds. We, therefore, investigated the variation between species focusing on GIPR desensitization and the role of the C-terminus. Experimental Approach Species variants of the GIPR were studied in vitro for endogenous ligand affinity, G protein activation (cAMP accumulation), recruitment of beta-arrestin, and internalization. Variants of the mouse, rat, and human GIPRs with swapped C-terminal tails were studied in parallel. Key Results The human GIPR is more prone to internalization than rodent GIPRs. Despite similar agonist affinities and potencies for Gαs-activation especially the mouse GIPR has a reduced receptor desensitization, internalization, and beta-arrestin recruitment. Using an enzyme-stable, long-acting GIP analogue, the species differences were even more pronounced. “Tail swapped” human, rat, and mouse GIPRs were all fully functional in their Gαs-coupling and the mouse GIPR regained internalization and beta-arrestin 2-recruitment properties with the human tail while the human GIPR lost the ability to recruit beta-arrestin 2 when its own C-terminus was replaced by the rat or mouse tail. Conclusion and Implications Desensitization of the human GIPR is dependent on the C-terminal tail. The diverse functionality of the C-terminal tail as well as receptor internalization patterns between species, especially human and mouse GIPRs, are important factors that could influence the preclinical therapeutic evaluation of GIPR targeting compounds.

Background and Purpose Metabotropic Glutamate Receptors (mGlu) regulate multiple functions in the nervous systems and are involved in multiple disorders. However, selectively targeting individual mGlu subtypes with spatiotemporal precision is still an unmet need. Photopharmacology can address this concern by means of photoswitchable compounds such as Optogluram, which is a positive allosteric modulator (PAM) of mGlu4 that enables to optically control physiological responses with a high precision. However, Optogluram is not fully selective and finding mGlu4 PAMs with subtype selectivity may be complicated. Experimental Approach New photoswitchable analogues of Optogluram were synthesised with the aim of obtaining photoswitchable PAMs selective for mGlu4 receptor and with improved photoisomerization properties. The photopharmacological profiles of these new compounds were assessed using spectroscopy, functional IP and cAMP assays and computational modelling. Key Results Optogluram-2 emerged as a new photoswitchable PAM for mGlu4 receptor and offered improved photoswitching properties and was selective for mGlu4. Optogluram-2 had activity as both PAM and allosteric agonist. The π-π stacking of the thiazole ring in the allosteric pocket of mGlu6 is hypothesised to be responsible of the mGlu4 selectivity. Conclusion and Implications. The enhanced photoswitching behaviour and improved selectivity of Optogluram-2 makes it an excellent candidate to study the role of mGlu4 with a high spatiotemporal precision that only photopharmacology can offer. Indeed, the use of Optogluram-2 in tissues where mGlu4 can be co-expressed with other mGlu receptors will help to unravel the complexity of mGlu receptors in neural transmission, pinpointing the role of mGlu4 in such systems.

Acute Respiratory Distress Syndrome is characterized by the accumulation of inflammatory fluid in the lung alveoli and is the main factor responsible for the high mortality in patients with COVID-19. In addition to the obvious pathogenic function of SARS-CoV-2 viral RNA, surface proteins, in particular, the Spike protein, which binds to the human angiotensin-converting enzyme 2 and is primed by the host serine protease TMPRSS2, play an important role in the development of the ARDS. The clinical worsening in the later phases of COVID-19 is thought to result from Spike protein binding to the pulmonary microvascular endothelium and epithelium, which leads to a damaged respiratory tract and ultimately a systemic inflammatory response or cytokine storm. In this study, we used our SARS-CoV-2 Spike protein Subunit 1-induced K18-hACE2 mouse model to develop an entirely new therapeutic strategy using the reversible, selective, allosteric inhibitor of PTP4A3 phosphatase KVX-053. Our findings suggest that this novel PTP4A3 inhibitor prevents or mitigates the initial pulmonary damage and halts the lethal cytokine storm.

Background: Advances in cancer treatment have caused the population of childhood cancer survivors (CCSs) to increase. CCSs are at risk of multiple therapy-related late effects (LEs). This study aims to evaluate the LE incidence and to assess how the body mass index (BMI) evolved in a CCS cohort from a Brazilian tertiary center. Methods: Retrospective cohort study with CCSs who received chemotherapy, radiotherapy, or both, seen in a follow-up clinic from 2002 to 2017. Anthropometric and clinical data were analyzed as descriptive statistics and hypothesis tests. LE cases were defined according to specific guidelines and classified into grades 1 to 4. The Z-scores of the participants’ BMI at diagnosis, treatment completion, and the last appointment at the clinic were compared. Results: The final sample included 245 CCSs; the median ages at diagnosis and recruiting were 7 and 16 years, respectively; the median follow-up period was 8.5 years. The most frequent diagnoses were acute lymphoblastic leukemia, central nervous system (CNS) tumors, and lymphomas. The LE incidence was 53.8% and included overweight/obesity (36.6%), hearing loss (34%), and thyroid gland abnormalities (32.8%). Treatment for medulloblastoma, Ewing sarcoma, and CNS tumors led to the highest LE incidence. In 66% of the participants, LEs were mild or moderate. The prevalence of overweight and obese participants was 24.4% and 12.2%, respectively. After treatment, the Z-scores of the participants’ BMI tended to increase over time, particularly in the groups aged 5–9 and 10–19 years. Conclusion: The LE incidence resembled the incidence reported in previous studies.

Botulinum neurotoxins are the most poisonous substances reported and listed in category ‘A’ of biowarfare agent. These neurotoxins cause flaccid paralysis of muscles by inhibiting acetylcholine release at the neuromuscular junction, and leads to death. The light chain (catalytic domain) is responsible for cleavage of SNAREs and inhibition of its activity stops the progress of neuroparalysis. Serotype identification is a time-consuming process; hence development of inhibitor against human botulism causing serotypes will be advantageous. Computer assisted screening approaches have been proved a proficient in silico method in the drug discovery and development. In present study, ligand-based in silico method was applied to identify the “hits” against human intoxicating BoNTs based on their binding affinities and ADMET analysis. A computational approach for docking 35 designed ligands to the catalytic domain of serotype BoNT/A; B; E and F, using Molegro Virtual Docker (MVD) and AutoDock suite was performed. The screening of the best ‘hits’ among the docked complexes was done on the basis of least docking score and common ligands, in both the programs. Analysis of molecular docking of the complexes shows a high binding affinity for the target with Moldock score between -139.85 and -88.24 kcal mol -1. Total five SMNPIs i.e., A9, A14, A15, A18 and A36 provided better binding affinities with the target protein BoNT/A (-109.17, -107.95, -103.12, -108.29, and -112.38 kcal mol -1), whereas for BoNT/B ligands A6, A10, and A31 has showed score of -112.56, -123.93 and -115.13 kcal mol -1. Ligands A6, A12, A18, and A24 exhibited the docking score ranged from -117.20 to -132.19 kcal mol -1 for BoNT/E, and for BoNT/F, only two ligands namely, A4 and A32 appeared to be potential inhibitors with the score of (-115.41, and -117.99 kcal mol -1). The designed ligands were expected to be less toxic considering the Lipinski, Ghose, Veber and Egan rules with a bioavailability score of 0.56. Therefore, in this study we identified ‘hits’ that could be further progressed for experimental studies leading to develop drug against botulism.

Phenological studies are essential to better understand forest community structure and dynamics, as well as climate influence on plant species. Tropical forests, such as the Amazon Forest, have significant plant-species biodiversity, mainly of woody species like Vouacapoua americana, which is an endangered species with great economic potential. The aim of the current study is to investigate the phenological behavior of species Vouacapoua americana Aubl – also known as ‘acapu’ – over a seven-year period (2016-2022). Thirty-five (35) individuals had the following reproductive phenophases assessed on a monthly basis, based on the treetop observation method: floral bud, anthesis, immature and mature fruits, and dispersion. Vegetative phenophases, such as abscission and leaf sprouting, were also assessed. Phenological analysis was carried out based on Principal Component Analysis (PCA), Circular analysis and Rayleigh test; all tests were performed in R software. Based on phenological results, reproductive phenophases have shown positive correlation to rainfall and relative humidity; the most intense reproductive phenophases were observed in the period accounting for the highest rainfall rate - from January to April. The most intense leaf phenophases were recorded in the dry season and presented positive correlation to both solar radiation and temperature. Acapu has proved to be a seasonal and annual species and this information can be used to help conservation programs, both ex situ and in situ, as well as the sustainable use of this species.

The issue of energy consumption has garnered significant interest due to its excessive usage. Recently, thermoelectric devices have been getting increased attention, as they can harness waste heat from various sources, such as solar radiation, human body, and industrial processes. Traditionally, the recovery of low-grade heat has been a challenge, resulting in unsustainable energy use and significant losses. While considerable advances have been made in thermoelectric materials in recent decades, the majority of these devices still primarily employ semiconductors. Nevertheless, the emergence of quasi-solid-state thermoelectric materials represents a novel devel-opment with profound promise for the environment and society. These materials offer several advantages, such as improved energy conversion capacities, cost-effectiveness, versatility, and scalability, to support increased usage. Additionally, this review explores the application of thermoelectric materials in self-powered sensors, integrated modules, and heat harvesting management. Lastly, the po-tential of high-performance thermocouples based on thermogalvanic effects is assessed, along with the challenges that must be over-come to realize this goal.

All-Polymer solar cells (all-PSCs) have attracted considerable attention due to their inherent advantages over other types of organic solar cells, including superior optical and thermal stability, as well as exceptional mechanical durability. Recently, all-PSCs have experi-enced remarkable advancements in device performance thanks to the invention of polymerized small-molecule acceptors (PSMAs) since 2017. Among these PSMAs, PY-IT has garnered immense interest from the scientific community due to its exceptional perfor-mance in all-PSCs. In this review, we presented the design principles of PY-IT and discussed the various strategies employed in device engineering for PY-IT-based all-PSCs. These strategies include additive and interface engineering, layer-by-layer processing methods, meniscus-assisted coating methods, and ternary strategy. Furthermore, this review highlighted several novel polymeric donor materials that are paired with PY-IT to achieve efficient all-PSCs. Lastly, we summarized the inspiring strategies for further advancing all-PSCs based on PY-IT. These strategies aim to enhance the overall performance and stability of all-PSCs by exploring new materials, optimizing device architectures, and improving fabrication techniques. By leveraging these approaches, we anticipate significant progress in the development of all-PSCs and their potential as a viable renewable energy source.

In grid-tied inverter (GTI) systems, the three-phase asymmetric LCL (A- LCL) filter has outstanding characteristics of simple structure, almost the smallest total inductance, and the strong resistance to the adverse effects of parameter shifts. Nevertheless, the order of this kind of power filter is high, and the control model is complicated due to its asymmetric structure. In this paper, a simplified modeling method, which effectively reduces the system order is proposed, without affecting the control performance. Then, the Kalman filter estimation (KF-estimation) is adopted to estimate the voltage at the point of common coupling (PCC) of the phase locked loop (PLL), which saves the voltage sensors, saves the costs, and improves the system’s ability to resist hardware failures. A 380 V/50 Hz/6 kW three-phase laboratory setup has been developed to verify the correctness and effectiveness of the proposed control method.

Mathematical formulas are essential tools for conveying mathematical concepts. Definitions of symbols in mathematical formulas often vary among different documents; thus, knowing the definitions is fundamental to grasping the semantics of the formulas. This research targets how to extract definitions of symbols representing variables from documents on chemical processes. We defined three features focusing on the unique usage of variable symbols and definitions in these documents and proposed a new variable definition extraction method. We compared the performance of the proposed method with that of a representative conventional method using 45 papers on five chemical processes. The proposed method achieved higher accuracy than the conventional one for four processes. We also demonstrated that our newly defined features contributed to the performance improvement and that the proposed method can achieve high accuracy with a small number of training datasets.

Regarding sugar and salt crystallization with large single crystals, the agglomerate thermodynamics and geometric morphologies, not the dynamics, dominate the particle size distribution (PSD). To consider this issue, a PSD design model is proposed for limited large crystal agglomeration. In this model, the agglomeration thermodynamic criticality is determined by estimating the adhesion and dispersion forces between single crystals. The geometric agglomerate morphologies are described by corresponding single crystal units stacking with porosity. By seed well-controlled of population, the key parameters of PSD (D01, D50 and D99) are precisely designed. For erythritol, the model design accuracies are 92%-99% in the 1.2 L and 10 L crystallizers, indicating that it can design PSD at various crystallization scales. Concerning the general research attention to microcrystal agglomeration kinetics (mostly active pharmaceutical ingredients), this model effectively guides the sugar and salt PSD design with limited large crystal agglomeration.

Background Allergic rhinitis (AR) is one of the most common chronic diseases worldwide. There are limited prospective long-term data regarding persistency and remission of AR. The objective of this study was to investigate the natural course of pollen-induced AR (pollen-AR) over 20 years, from childhood into early adulthood. Methods Data from 1137 subjects in the Barn/Children Allergi/Allergy Milieu Stockholm Epidemiologic birth cohort (BAMSE) with a completed questionnaire regarding symptoms, asthma, treatment with allergen immunotherapy (AIT) and results of allergen-specific IgE for inhalant allergens at 4, 8, 16 and 24 years were analysed. Pollen-AR was defined as sneezing, runny, itchy, or blocked nose; and itchy or watery eyes when exposed to birch and/or grass pollen in combination with allergen-specific IgE ≥0.35kU A/l to birch and/or grass. Results Approximately 75% of children with pollen-AR at 4 or 8 years had persistent disease up to 24 years, and 30% developed asthma. The probability of persistency was high already at low levels of pollen-specific IgE. The highest rate of remission from pollen-AR was seen between 16 and 24 years (21.5%), however the majority remained sensitized. This period was also when pollen-specific IgE-levels stopped increasing and the average estimated annual incidence of pollen-AR decreased from 1.5% to 0.8% per year. Conclusion Children with pollen-AR are at high risk of persistent disease for at least 20 years. Childhood up to adolescence seems to be the most dynamic period of AR progression. Our findings underline the close cross-sectional and longitudinal relationship between sensitization, AR, and asthma.