bluuebunny/crossref_metadata_2025_split huggingface dataset:
(Il)legitimacy of international intellectual property regime?
Authors: Çapar Gürkan 
Published: April 2023

AbstractThe recent Covid-19 global health crisis not only brings into sharp relief the current problems afflicting the international intellectual property regime (IIPR) but also calls into question its legitimacy as an international authority. Against this backdrop, the article aims to launch an investigation into the legitimacy of the IIPR, as an international co-ordinative authority, designed to protect IP rights without prejudice to international trade norms. Drawing on Raz’s service conception of authority, it explores whether the IIPR lives up to its promises by enabling co-ordination between states over IP rights without undermining the initial balance on which it is founded, struck between developing and developed countries, as well as between international protection of IP- cum-trade rights and domestic regulatory autonomy. It does so by classifying the historical evolution of the IIPR under three different phases: (i) its foundation, (ii) before, and (iii) after the TRIPS-plus. Upon showing the legitimacy challenges inherent in its undemocratic foundation, the article points to the success of the regime in finding a balance between conflicting interests before the TRIPS-plus era. Later, it underlines the many challenges that come with linking the IIPR to the investment regime and argues that the FTAs and frequent regime-shifting activities put further pressure on the authority and legitimacy of the regime. Stressing the importance of democratic participation for the legitimacy of any co-ordinative authority, the article casts doubt on the IIPR’s legitimacy and concludes by raising some points to overcome the ongoing legitimacy challenges.
Accounting for Mexican business cycles
Authors: Brinca Pedro , Costa Filho João Ricardo 
Published: April 2023

AbstractThe Mexican economy experienced two large crises: in 1995 and in 2008. The dynamics and origins of the episodes are very different; nevertheless, is there a common underlying mechanism? First, by applying the Business Cycle Accounting method, we find that the efficiency wedge is the main driver of output during both episodes. We present an equivalence between the neoclassical growth model with distortions and a small open economy with imported intermediate goods inputs, in which relative price changes manifest themselves as changes on the efficiency wedge. This result proposes a solution for the theoretical puzzle regarding the relationship between terms of trade shocks and productivity. Finally, the model is able to reproduce both the intensities and velocities of the crises in Mexico.
Assessing Future Projections of Warm‐Season Marine Heatwave Characteristics With Three CMIP6 Models
Authors: Li Xinru , Donner Simon 
Published: April 2023

AbstractMarine heatwaves in the summertime when temperatures may exceed organisms' thermal thresholds (“warm‐season marine heatwaves (MHWs)”) have huge impacts on the health and function of ecosystems like kelp forests and coral reefs. While previous studies showed that MHWs are likely to become more frequent and severe under future climate change, there has been less analysis of the thermal properties of warm‐season MHWs or on the effects of climate model biases on these projections. In this study, we examine CMIP6 model ability to simulate five key thermal properties of warm‐season MHWs, and evaluate the global pattern of future projections for coral reef and kelp systems. The results show that the duration, accumulated heat stress and peak intensity are projected to increase by >60 days, 160°C·day and 1°C, respectively, across most of the ocean by the end of the 21st century. In contrast, the duration of “priming” (a period of sub‐lethal heat stress prior to substantial MHW heat stress) is projected to decrease by >30 days in the tropics, potentially reducing organisms' ability to acclimate to heat stress. The projected increases in MHW duration and accumulated heat stress in some coral reef and kelp forest locations, however, are likely overestimated due to model limitations in simulating surface winds, deep convection and some other processes that influence MHW evolution. The findings point to some possible processes to target in model development and regional biases to be considered when projecting the impacts of MHWs on marine ecosystems.
The Evolution of Whistler Hiss‐Like Waves Across Plasmapause: Hiss to Exohiss
Authors: Feng Bopu , Li Haimeng , Yu Xiongdong , Yuan Zhigang , Tang Rongxin , Wang Dedong , Ouyang Zhihai , Deng Xiaohua 
Published: April 2023

AbstractThe exohiss waves are hiss‐like whistler mode waves that occur outside plasmapause. Although these waves can cause the loss of radiation belt electrons ∼<MeV through resonant scattering, the formation and evolution processes of exohiss waves remain incompletely covered yet. In this letter, by virtue of measurement from Van Allen Probes and ray tracing simulation, we provide a direct observational evidence for the origin of exohiss waves. We analyze the evolution of power spectrum density of hiss‐like whistler waves during their propagation. The results suggest that exohiss waves originate from mixed result of hiss waves leaked out from different L shells inside the plasmapause. Additionally, we found that frequencies of exohiss waves are primarily below 700 Hz, it is probably because the hiss waves with higher frequencies experience more severe Landau damping. Our results significantly improve understanding of the evolution of whistler waves in radiation belts.
Palliative Care Interventions Among Adolescents and Young Adults With Serious Illness: A Scoping Review
Authors: Newman Amy R. , Kenney Ansley E. , Witkowski Elizabeth , Karst Jeffrey , Lerret Stacee , Davies W. Hobart , Rothschild Charles B. 
Published: April 2023

Objective: To map the range of multidisciplinary palliative care interventions that are available to adolescents and young adults (AYAs) with serious illness. Methods: Scoping review methodology as outlined by Arksey and O’Malley. Results: Twenty-two articles describing nine specific AYA-focused, multidisciplinary palliative care interventions were included in this review. Interventions focused on supporting advance care planning, facilitating treatment decision making, managing pain, and promoting resilience, psychosocial well-being, and quality of life. Interventions were delivered face-to-face and via different eHealth platforms and were targeted to AYAs with cancer, HIV/AIDS, and cystic fibrosis in both inpatient and outpatient settings. Conclusions: Few evidence-based multidisciplinary palliative care interventions have documented benefits for AYAs with serious illness. The limited work that has been done demonstrates that AYAs are open to engaging in palliative care interventions and suggests that individual members of the multidisciplinary team can implement these different interventions to support enhanced patient outcomes. Implications for Impact Statement Adolescents and young adults with serious illness benefit from palliative care interventions, yet only a limited number of interventions have been developed to meet their unique physical, psychological, and developmental needs. Pediatric psychologists can contribute to the development and implementation of interventions aimed to enhance the quality of life and illness experience among these patients.
Adapter CAR T cells to counteract T-cell exhaustion and enable flexible targeting in AML
Authors: Nixdorf D. , Sponheimer M. , Berghammer D. , Engert F. , Bader U. , Philipp N. , Kazerani M. , Straub T. , Rohrbacher L. , Wange L. , Dapa S. , Atar D. , Seitz C. M. , Brandstetter K. , Linder A. , von Bergwelt M. , Leonhardt H. , Mittelstaet J. , Kaiser A. , Bücklein V. , Subklewe M. 
Published: April 2023

AbstractAlthough the landscape for treating acute myeloid leukemia (AML) patients has changed substantially in recent years, the majority of patients will eventually relapse and succumb to their disease. Allogeneic stem cell transplantation provides the best anti-AML treatment strategy, but is only suitable in a minority of patients. In contrast to B-cell neoplasias, chimeric antigen receptor (CAR) T-cell therapy in AML has encountered challenges in target antigen heterogeneity, safety, and T-cell dysfunction. We established a Fab-based adapter CAR (AdCAR) T-cell platform with flexibility of targeting and control of AdCAR T-cell activation. Utilizing AML cell lines and a long-term culture assay for primary AML cells, we were able to demonstrate AML-specific cytotoxicity using anti-CD33, anti-CD123, and anti-CLL1 adapter molecules in vitro and in vivo. Notably, we show for the first time the feasibility of sequential application of adapter molecules of different specificity in primary AML co-cultures. Importantly, using the AML platform, we were able to demonstrate that chronic T-cell stimulation and exhaustion can be counteracted through introduction of treatment-free intervals. As T-cell exhaustion and target antigen heterogeneity are well-known causes of resistance, the AdCAR platform might offer effective strategies to ameliorate these limitations.
3D Printing and processing of miniaturized transducers with near-pristine piezoelectric ceramics for localized cavitation
Authors: Lu Haotian , Cui Huachen , Lu Gengxi , Jiang Laiming , Hensleigh Ryan , Zeng Yushun , Rayes Adnan , Panduranga Mohanchandra K. , Acharya Megha , Wang Zhen , Irimia Andrei , Wu Felix , Carman Gregory P. , Morales José M. , Putterman Seth , Martin Lane W. , Zhou Qifa , Zheng Xiaoyu 
Published: April 2023

AbstractThe performance of ultrasonic transducers is largely determined by the piezoelectric properties and geometries of their active elements. Due to the brittle nature of piezoceramics, existing processing tools for piezoelectric elements only achieve simple geometries, including flat disks, cylinders, cubes and rings. While advances in additive manufacturing give rise to free-form fabrication of piezoceramics, the resultant transducers suffer from high porosity, weak piezoelectric responses, and limited geometrical flexibility. We introduce optimized piezoceramic printing and processing strategies to produce highly responsive piezoelectric microtransducers that operate at ultrasonic frequencies. The 3D printed dense piezoelectric elements achieve high piezoelectric coefficients and complex architectures. The resulting piezoelectric charge constant, d33, and coupling factor, kt, of the 3D printed piezoceramic reach 583 pC/N and 0.57, approaching the properties of pristine ceramics. The integrated printing of transducer packaging materials and 3D printed piezoceramics with microarchitectures create opportunities for miniaturized piezoelectric ultrasound transducers capable of acoustic focusing and localized cavitation within millimeter-sized channels, leading to miniaturized ultrasonic devices that enable a wide range of biomedical applications.
Expression-based subtypes define pathologic response to neoadjuvant immune-checkpoint inhibitors in muscle-invasive bladder cancer
Authors: Robertson A. Gordon , Meghani Khyati , Cooley Lauren Folgosa , McLaughlin Kimberly A. , Fall Leigh Ann , Yu Yanni , Castro Mauro A. A. , Groeneveld Clarice S. , de Reyniès Aurélien , Nazarov Vadim I. , Tsvetkov Vasily O. , Choy Bonnie , Raggi Daniele , Marandino Laura , Montorsi Francesco , Powles Thomas , Necchi Andrea , Meeks Joshua J. 
Published: April 2023

AbstractCheckpoint immunotherapy (CPI) has increased survival for some patients with advanced-stage bladder cancer (BCa). However, most patients do not respond. Here, we characterized the tumor and immune microenvironment in pre- and post-treatment tumors from the PURE01 neoadjuvant pembrolizumab immunotherapy trial, using a consolidative approach that combined transcriptional and genetic profiling with digital spatial profiling. We identify five distinctive genetic and transcriptomic programs and validate these in an independent neoadjuvant CPI trial to identify the features of response or resistance to CPI. By modeling the regulatory network, we identify the histone demethylase KDM5B as a repressor of tumor immune signaling pathways in one resistant subtype (S1, Luminal-excluded) and demonstrate that inhibition of KDM5B enhances immunogenicity in FGFR3-mutated BCa cells. Our study identifies signatures associated with response to CPI that can be used to molecularly stratify patients and suggests therapeutic alternatives for subtypes with poor response to neoadjuvant immunotherapy.
What the geological past can tell us about the future of the ocean’s twilight zone
Authors: Crichton Katherine A. , Wilson Jamie D. , Ridgwell Andy , Boscolo-Galazzo Flavia , John Eleanor H. , Wade Bridget S. , Pearson Paul N. 
Published: April 2023

AbstractPaleontological reconstructions of plankton community structure during warm periods of the Cenozoic (last 66 million years) reveal that deep-dwelling ‘twilight zone’ (200–1000 m) plankton were less abundant and diverse, and lived much closer to the surface, than in colder, more recent climates. We suggest that this is a consequence of temperature’s role in controlling the rate that sinking organic matter is broken down and metabolized by bacteria, a process that occurs faster at warmer temperatures. In a warmer ocean, a smaller fraction of organic matter reaches the ocean interior, affecting food supply and dissolved oxygen availability at depth. Using an Earth system model that has been evaluated against paleo observations, we illustrate how anthropogenic warming may impact future carbon cycling and twilight zone ecology. Our findings suggest that significant changes are already underway, and without strong emissions mitigation, widespread ecological disruption in the twilight zone is likely by 2100, with effects spanning millennia thereafter.
Exploiting synergistic effect of CO/NO gases for soft tissue transplantation using a hydrogel patch
Authors: Tang Xiaoduo , Ren Jingyan , Wei Xin , Wang Tao , Li Haiqiu , Sun Yihan , Liu Yang , Chi Mingli , Zhu Shoujun , Lu Laijin , Zhang Junhu , Yang Bai 
Published: April 2023

AbstractAutologous skin flap transplantation is a common method for repairing complex soft tissue defects caused by cancer, trauma, and congenital malformations. Limited blood supply range and post-transplantation ischemia-reperfusion injury can lead to distal necrosis of the flap and long-term functional loss, which severely restricts the decision-making regarding the optimal surgical plan. To address this issue, we develop a hydrogel patch that releases carbon monoxide and nitric oxide gases on demand, to afford a timely blood supply for skin flap transplantation during surgery. Using an ischemia-reperfusion dorsal skin flap model in rats, we show that the hydrogel patch maintains the immediate opening of blood flow channels in transplanted tissue and effective blood perfusion throughout the perioperative period, activating perfusion of the hemodynamic donor site. We demonstrate that the hydrogel patch promotes distal vascularization and long-term functional reconstruction of transplanted tissues by inhibiting inflammatory damage and accelerating blood vessel formation.
Cryo-EM structures of Trypanosoma brucei gambiense ISG65 with human complement C3 and C3b and their roles in alternative pathway restriction
Authors: Sülzen Hagen , Began Jakub , Dhillon Arun , Kereïche Sami , Pompach Petr , Votrubova Jitka , Zahedifard Farnaz , Šubrtova Adriana , Šafner Marie , Hubalek Martin , Thompson Maaike , Zoltner Martin , Zoll Sebastian 
Published: April 2023

AbstractAfrican Trypanosomes have developed elaborate mechanisms to escape the adaptive immune response, but little is known about complement evasion particularly at the early stage of infection. Here we show that ISG65 of the human-infective parasite Trypanosoma brucei gambiense is a receptor for human complement factor C3 and its activation fragments and that it takes over a role in selective inhibition of the alternative pathway C5 convertase and thus abrogation of the terminal pathway. No deposition of C4b, as part of the classical and lectin pathway convertases, was detected on trypanosomes. We present the cryo-electron microscopy (EM) structures of native C3 and C3b in complex with ISG65 which reveal a set of modes of complement interaction. Based on these findings, we propose a model for receptor-ligand interactions as they occur at the plasma membrane of blood-stage trypanosomes and may facilitate innate immune escape of the parasite.
Giant dynamic electromechanical response via field driven pseudo-ergodicity in nonergodic relaxors
Authors: Qi He , Hu Tengfei , Deng Shiqing , Liu Hui , Fu Zhengqian , Chen Jun 
Published: April 2023

AbstractEnhanced electromechanical response can commonly be found during the crossover from normal to relaxor ferroelectric state, making relaxors to be potential candidates for actuators. In this work, (Pb0.917La0.083)(Zr0.65Ti0.35)0.97925O3 ceramic was taken as a case study, which shows a critical nonergodic state with both double-like P-E loop and irreversible relaxor-normal ferroelectric phase after poling at room temperature. The low-hysteresis linear-like S-P2 loop, in-situ synchrotron X-ray diffraction and transmission electron microscope results suggest that the nonpolar relaxor state acts as a bridge during polarization reorientation process, accompanying which lattice strain contributes to 61.8% of the total strain. In other words, the transformation from normal ferroelectric to nonergodic relaxor state could be triggered by electric field through polarization contraction, which could change to be spontaneously with slightly increasing temperature in the nonergodic relaxor zone. Therefore, pseudo-ergodicity in nonergodic relaxors (i.e. reversible nonergodic-normal ferroelectric phase transition) driven by periodic electric field should be the main mechanism for obtaining large electrostrain close to the nonergodic-ergodic relaxor boundary. This work provides new insights into polarization reorientation process in relaxor ferroelectrics, especially phase instability in nonergodic relaxor zone approaching to freezing temperature.
Coherent hexagonal platinum skin on nickel nanocrystals for enhanced hydrogen evolution activity
Authors: Liu Kai , Yang Hao , Jiang Yilan , Liu Zhaojun , Zhang Shumeng , Zhang Zhixue , Qiao Zhun , Lu Yiming , Cheng Tao , Terasaki Osamu , Zhang Qing , Gao Chuanbo 
Published: April 2023

AbstractMetastable noble metal nanocrystals may exhibit distinctive catalytic properties to address the sluggish kinetics of many important processes, including the hydrogen evolution reaction under alkaline conditions for water-electrolysis hydrogen production. However, the exploration of metastable noble metal nanocrystals is still in its infancy and suffers from a lack of sufficient synthesis and electronic engineering strategies to fully stimulate their potential in catalysis. In this paper, we report a synthesis of metastable hexagonal Pt nanostructures by coherent growth on 3d transition metal nanocrystals such as Ni without involving galvanic replacement reaction, which expands the frontier of the phase-replication synthesis. Unlike noble metal substrates, the 3d transition metal substrate owns more crystal phases and lower cost and endows the hexagonal Pt skin with substantial compressive strains and programmable charge density, making the electronic properties particularly preferred for the alkaline hydrogen evolution reaction. The energy barriers are greatly reduced, pushing the activity to 133 mA cmgeo–2 and 17.4 mA μgPt–1 at –70 mV with 1.5 µg of Pt in 1 M KOH. Our strategy paves the way for metastable noble metal catalysts with tailored electronic properties for highly efficient and cost-effective energy conversion.
A computational analysis of mouse behavior in the sucrose preference test
Authors: Verharen Jeroen P. H. , de Jong Johannes W. , Zhu Yichen , Lammel Stephan 
Published: April 2023

AbstractThe sucrose preference test (SPT) measures the relative preference of sucrose over water to assess hedonic behaviors in rodents. Yet, it remains uncertain to what extent the SPT reflects other behavioral components, such as learning, memory, motivation, and choice. Here, we conducted an experimental and computational decomposition of mouse behavior in the SPT and discovered previously unrecognized behavioral subcomponents associated with changes in sucrose preference. We show that acute and chronic stress have sex-dependent effects on sucrose preference, but anhedonia was observed only in response to chronic stress in male mice. Additionally, reduced sucrose preference induced by optogenetics is not always indicative of anhedonia but can also reflect learning deficits. Even small variations in experimental conditions influence behavior, task outcome and interpretation. Thus, an ostensibly simple behavioral task can entail high levels of complexity, demonstrating the need for careful dissection of behavior into its subcomponents when studying the underlying neurobiology.
Pathway choice in the alternative telomere lengthening in neoplasia is dictated by replication fork processing mediated by EXD2’s nuclease activity
Authors: Broderick Ronan , Cherdyntseva Veronica , Nieminuszczy Jadwiga , Dragona Eleni , Kyriakaki Maria , Evmorfopoulou Theodora , Gagos Sarantis , Niedzwiedz Wojciech 
Published: April 2023

AbstractTelomerase-independent cancer proliferation via the alternative lengthening of telomeres (ALT) relies upon two distinct, largely uncharacterized, break-induced-replication (BIR) processes. How cancer cells initiate and regulate these terminal repair mechanisms is unknown. Here, we establish that the EXD2 nuclease is recruited to ALT telomeres to direct their maintenance. We demonstrate that EXD2 loss leads to telomere shortening, elevated telomeric sister chromatid exchanges, C-circle formation as well as BIR-mediated telomeric replication. We discover that EXD2 fork-processing activity triggers a switch between RAD52-dependent and -independent ALT-associated BIR. The latter is suppressed by EXD2 but depends specifically on the fork remodeler SMARCAL1 and the MUS81 nuclease. Thus, our findings suggest that processing of stalled replication forks orchestrates elongation pathway choice at ALT telomeres. Finally, we show that co-depletion of EXD2 with BLM, DNA2 or POLD3 confers synthetic lethality in ALT cells, identifying EXD2 as a potential druggable target for ALT-reliant cancers.
Engineering protein-based therapeutics through structural and chemical design
Authors: Ebrahimi Sasha B. , Samanta Devleena 
Published: April 2023

AbstractProtein-based therapeutics have led to new paradigms in disease treatment. Projected to be half of the top ten selling drugs in 2023, proteins have emerged as rivaling and, in some cases, superior alternatives to historically used small molecule-based medicines. This review chronicles both well-established and emerging design strategies that have enabled this paradigm shift by transforming protein-based structures that are often prone to denaturation, degradation, and aggregation in vitro and in vivo into highly effective therapeutics. In particular, we discuss strategies for creating structures with increased affinity and targetability, enhanced in vivo stability and pharmacokinetics, improved cell permeability, and reduced amounts of undesired immunogenicity.