bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pricing strategies, executive committee power and negotiation leverage in New Zealand's containment of public spending on pharmaceuticals
Authors: Main Ben , Csanadi Marcell , Ozieranski Piotr 
Published: April 2022

AbstractThis paper explores policy mechanisms behind New Zealand's remarkable track record of cost containment in public pharmaceutical spending, contrasting with most other advanced economies. We drew on a review of official policy documents and 28 semi-structured expert interviews. We found that decision making in pricing and reimbursement policy was dominated by a small group of managers at the Pharmaceutical Management Agency (PHARMAC), the country's drug reimbursement and Health Technology Assessment Agency, who negotiated pharmaceutical prices on behalf of the public payer. In formal negotiation over patented pharmaceutical prices these managers applied an array of pricing strategies, most notably, ‘bundling’ consisting of discounted package deals for multiple pharmaceuticals, and ‘play-off tenders’, whereby two or more pharmaceutical companies bid for exclusive contracts. The key pricing strategy for generic drugs, in contrast, was ‘blind-tenders’ taking the form of an annual bidding process for supply contracts. An additional contextual condition on bargaining over pharmaceutical prices was an indirect strategy that involved the cultivation of the PHARMAC's ‘negotiation leverage’. We derived two cost containment mechanisms consisting in the relationship between pricing strategy options and various reimbursement actors. Our findings shed light on aspects of the institutional design of drug reimbursement that may promote the effective use of competitive negotiations of pharmaceutical prices, including specific pricing strategies, by specialist public payer institutions. On this basis, we formulate recommendations for countries seeking to develop or reform policy frameworks to better meet the budgetary challenge posed by pharmaceutical expenditure.
Marginally housed or marginally homeless?
Authors: Laurie Emma 
Published: April 2022

AbstractThe English homelessness scheme has been lauded as being one of the most progressive in the world for offering an individually legally enforceable right to housing to those people who meet the statutory criteria. Its definition of homelessness is also liberal by comparison with many other countries within Europe and beyond, extending significantly beyond the stereotypical rooflessness experienced by rough sleepers. Nevertheless, the scheme is highly selective and targeted, and assesses homelessness through a test of relative need, rather than enshrining a minimally acceptable standard of housing. It thereby creates a category of the marginally housed whose housing needs are assessed as insufficiently poor to be officially categorised as homeless, yet who are living in severely inadequate housing. To reduce the uncertainty and contingency of the current test, the paper proposes the adoption of a new test of habitability.
A Case Study Investigation of Year 8 Students’ Experiences with Online Learning Through the Padlet App in a State-Maintained Girls’ Grammar School
Authors: Cleary Caolain J. 
Published: April 2022

AbstractIf the past two years have proven anything, it is that students today hold a tremendous capacity to adapt to incredibly difficult learning environments. This paper explores student learning experiences in one such learning environment, the period of online learning that occurred between January and March 2021 due to COVID-19-related school closures. Investigating the effectiveness of the digital learning platform Padlet in terms of student engagement with the Latin curriculum and its cultivation of Latin comprehension skills, this case study of Year 8 students in a state-maintained girls’ grammar school demonstrates the value of collaborative, discussion-based approaches to remote teaching. The value of digital learning platforms in our post-pandemic educational environment is demonstrated in its potential to bridge the communicative gap felt by many students when taught online, simulating the lively classroom climate which so often generates exciting and effective learning opportunities for each student. As this paper demonstrates, digital learning platforms hold the potential not only to assist educators in coping with the challenges of remote learning, but also to extend student learning in ways once considered unimaginable beyond the realms of the physical classroom. As a result, this paper argues that the position of such platforms in the post-pandemic classroom must be advocated and supported further.
ENTICE Satellite Orbital Simulator to Study Ice Clouds
Authors: Johnson Kyle , Jiang Jonathan H. , Yue Qing , Fahy Kristen A. , Palo Scott 
Published: April 2022

AbstractClouds play a significant role in the Earth's energy balance and hydrologic cycle through their effects on radiation and precipitation, and therefore are crucial for life on Earth. Earth's NexT‐generation ICE mission (ENTICE) is proposed to measure diurnally resolved global vertical profiles of cloud ice particle size, ice water content, and in‐cloud humidity and temperature combining a 94 GHz cloud radar and multi‐frequency sub‐millimeter (sub‐mm) microwave radiometers from space. The scientific objective of ENTICE is to identify the important processes by which anvil clouds evolve and interact with ambient thermodynamic conditions to advance our fundamental understanding of clouds and reduce uncertainties in cloud climate feedback. Whether such a science objective could be achieved depends on the orbital sampling characteristics of the mission. In this study, ENTICE sampling statistics are simulated with more than 1 billion (109) profiles and using five different scanning methods in a 400 km altitude precession orbit with an inclination of 65°: nadir, forward pointing, side scanning, and conical scanning for the radiometers, and nadir pointing for the radar. These statistics can then be used to help with future mission planning efforts. Using the GEOS‐5 model atmosphere (produced by nature‐run at 7‐km and 30‐min resolution), the simulator calculates sampling statistics related to cloud types and overpass times with enhancement from radar. The wide swath of ENTICE radiometers by conical and side scanning methods ensures ample high cloud samples (1.3 × 109 samples) gathered by ENTICE over its 2‐year mission for different types of clouds with sufficient sampling over the diurnal cycles. Sampling differences between radar and radiometers at nadir shows the combination of radar and radiometers will allow for measurements of cloud vertical profiles. Therefore, our results show that the designed orbit sampling of ENTICE is sufficient to fulfill the mission science goals.
Dynamics of Mixed Clathrate‐Ice Shells on Ocean Worlds
Authors: Carnahan Evan , Vance Steven D. , Hesse Marc A. , Journaux Baptiste , Sotin Christophe 
Published: April 2022

AbstractThe habitability of oceans within icy worlds depends on material and heat transport through their outer ice shells. Previous work shows a methane clathrate layer at the upper surface of the ice shell of Titan thickens the convecting region, while on Pluto a clathrate layer at the base of the ice shell hinders convection. In this way, the dynamics of clathrate‐ice shells may be essential to the thermal evolution and habitability of ocean worlds. However, studies to date have not addressed the dynamics that determine the location of clathrates within the ice shell. Here, we show that, in contrast to previous studies, clathrates accumulating at the base of the ice shell are entrained throughout the shell. Clathrates are stiffer than ice. As a result, entrainment slows convection and thickens the conductive lid across a range of ocean worlds, potentially preserving sub‐ice oceans but limiting avenues for material transport into them.
Alternating Emission Features in Io's Footprint Tail: Magnetohydrodynamical Simulations of Possible Causes
Authors: Schlegel Stephan , Saur Joachim 
Published: April 2022

AbstractIo's movement relative to the plasma in Jupiter's magnetosphere creates Alfvén waves propagating along the magnetic field lines which are partially reflected along their path. These waves are the root cause for auroral emission, which is subdivided into the Io Footprint (IFP), its tail and leading spot. New observations of the Juno spacecraft by Mura et al. (2018, https://doi.org/10.1126/science.aat1450) have shown puzzling substructure of the footprint and its tail. In these observations, the symmetry between the poleward and equatorward part of the footprint tail is broken and the tail spots are alternatingly displaced. We show that the location of these bright spots in the tail are consistent with Alfvén waves reflected at the boundary of the Io torus and Jupiter's ionosphere. Then, we investigate three different mechanisms to explain this phenomenon: (a) The Hall effect in Io's ionosphere, (b) travel time differences of Alfvén waves between Io's Jupiter facing and its opposing side and (c) asymmetries in Io's atmosphere. For that, we use magnetohydrodynamic simulations within an idealized geometry of the system. We use the Poynting flux near the Jovian ionosphere as a proxy for the morphology of the generated footprint and its tail. We find that the Hall effect is the most important mechanism under consideration to break the symmetry causing the “Alternating Alfvén spot street.” The travel time differences contributes to enhance this effect. We find no evidence that the inhomogeneities in Io's atmosphere contribute significantly to the location or shape of the tail spots.
Effects of Temperature and Salinity on Surface Currents in the Equatorial Pacific
Authors: Chen Lu , Zhang Rong‐Hua , Gao Chuan 
Published: April 2022

AbstractSurface currents in the equatorial Pacific play a key role in determining thermohaline structures in the upper ocean, thus acting to modulate the tropical Pacific mean state and interannual variability. In turn, the thermohaline structure and its variability can also affect surface currents by changing ocean density and pressure gradients. Currently, the thermohaline effects on the surface currents have not been well understood, especially for the salinity role. In this study, the thermohaline effects on surface currents in the equatorial Pacific are systematically evaluated based on an analytical scheme, which is used to calculate surface currents in producing the Ocean Surface Current Analysis Real‐time (OSCAR) product. Several calculations are performed with the original OSCAR‐based scheme and an improved scheme including the salinity effect. It is demonstrated that the thermohaline effects are generally dominated by the temperature role, but the salinity effect plays a non‐negligible role near the dateline and in the far eastern Pacific. The thermohaline effects are quantified and highlighted on seasonal and interannual time scales. For annual mean surface currents, temperature and salinity effects work together to weaken zonal currents north of the equator, with their reduced amplitude by about half. Seasonally, the thermohaline effects are dominant in spring due to the weakened wind effect. Interannually, the salinity effect explains up to 25% of the total variance in the far eastern equatorial Pacific. This study highlights the substantial contributions of thermohaline anomalies to surface current variabilities, in which salinity can play an important contributing role.
Fire and Ice: The Impact of Wildfire‐Affected Albedo and Irradiance on Glacier Melt
Authors: Aubry‐Wake Caroline , Bertoncini André , Pomeroy John W. 
Published: April 2022

AbstractWildfire occurrence and severity is predicted to increase in the upcoming decades with severe negative impacts on human societies. The impacts of upwind wildfire activity on glacier melt, a critical source of freshwater for downstream environments, were investigated through analysis of field and remote sensing observations and modeling experiments for the 2015–2020 melt seasons at the well‐instrumented Athabasca Glacier in the Canadian Rockies. Upwind wildfire activity influenced surface glacier melt through both a decrease in the surface albedo from deposition of soot on the glacier and through the impact of smoke on atmospheric conditions above the glacier. Athabasca Glacier on‐ice weather station observations show days with dense smoke were warmer than clear, non‐smoky days, and sustained a reduction in surface shortwave irradiance of 103 W m−2 during peak shortwave irradiance and an increase in longwave irradiance of 10 W m−2, producing an average 15 W m−2 decrease in net radiation. Albedo observed on‐ice gradually decreased after the wildfires started, from a summer average of 0.29 in 2015 before the wildfires to as low as 0.16 in 2018 after extensive wildfires and remained low for two more melt seasons without substantial upwind wildfires. Reduced all‐wave irradiance partly compensated for the increase in melt due to lowered albedo in those seasons when smoke was detected above Athabasca Glacier. In melt seasons without smoke, the suppressed albedo increased melt by slightly more than 10% compared to the simulations without fire‐impacted albedo, increasing melt by 0.42 m. w.e. in 2019 and 0.37 m. w.e. in 2020.
Structural color printing via polymer-assisted photochemical deposition
Authors: Choi Shinhyuk , Zhao Zhi , Zuo Jiawei , Faruque Hossain Mansur Resalat , Yao Yu , Wang Chao 
Published: April 2022

AbstractStructural color printings have broad applications due to their advantages of long-term sustainability, eco-friendly manufacturing, and ultra-high resolution. However, most of them require costly and time-consuming fabrication processes from nanolithography to vacuum deposition and etching. Here, we demonstrate a new color printing technology based on polymer-assisted photochemical metal deposition (PPD), a room temperature, ambient, and additive manufacturing process without requiring heating, vacuum deposition or etching. The PPD-printed silver films comprise densely aggregated silver nanoparticles filled with a small amount (estimated <20% volume) of polymers, producing a smooth surface (roughness 2.5 nm) even better than vacuum-deposited silver films (roughness 2.8 nm) at ~4 nm thickness. Further, the printed composite films have a much larger effective refractive index n (~1.90) and a smaller extinction coefficient k (~0.92) than PVD ones in the visible wavelength range (400 to 800 nm), therefore modulating the surface reflection and the phase accumulation. The capability of PPD in printing both ultra-thin (~5 nm) composite films and highly reflective thicker film greatly benefit the design and construction of multilayered Fabry–Perot (FP) cavity structures to exhibit vivid and saturated colors. We demonstrated programmed printing of complex pictures of different color schemes at a high spatial resolution of ~6.5 μm by three-dimensionally modulating the top composite film geometries and dielectric spacer thicknesses (75 to 200 nm). Finally, PPD-based color picture printing is demonstrated on a wide range of substrates, including glass, PDMS, and plastic, proving its broad potential in future applications from security labeling to color displays.
HspBP1 is a dual function regulatory protein that controls both DNA repair and apoptosis in breast cancer cells
Authors: Youn Cha Kyung , Lee Jung-Hee , Hariharasudhan Gurusamy , Kim Hong Beum , Kim Jeeho , Lee Sumi , Lim Sung-Chul , Yoon Sang-Pil , Park Sang-Gon , Chang In-Youb , You Ho Jin 
Published: April 2022

AbstractThe Hsp70-binding protein 1 (HspBP1) belongs to a family of co-chaperones that regulate Hsp70 activity and whose biological significance is not well understood. In the present study, we show that when HspBP1 is either knocked down or overexpressed in BRCA1-proficient breast cancer cells, there were profound changes in tumorigenesis, including anchorage-independent cell growth in vitro and in tumor formation in xenograft models. However, HspBP1 did not affect tumorigenic properties in BRCA1-deficient breast cancer cells. The mechanisms underlying HspBP1-induced tumor suppression were found to include interactions with BRCA1 and promotion of BRCA1-mediated homologous recombination DNA repair, suggesting that HspBP1 contributes to the suppression of breast cancer by regulating BRCA1 function and thereby maintaining genomic stability. Interestingly, independent of BRCA1 status, HspBP1 facilitates cell survival in response to ionizing radiation (IR) by interfering with the association of Hsp70 and apoptotic protease-activating factor-1. These findings suggest that decreased HspBP1 expression, a common occurrence in high-grade and metastatic breast cancers, leads to genomic instability and enables resistance to IR treatment.
TNFAIP8 protein functions as a tumor suppressor in inflammation-associated colorectal tumorigenesis
Authors: Lou Yunwei , Tian Xueqin , Sun Chen , Song Miaomiao , Han Meijuan , Zhao Yuxin , Song Yaru , Song Xiangfeng , Zhang Wen , Chen Youhai H. , Wang Hui 
Published: April 2022

AbstractTumor necrosis factor-α-induced protein 8 (TNFAIP8 or TIPE) is a member of the TNFAIP8 family. While TIPE was broadly considered to be pro-cancerous, its precise roles in carcinogenesis especially those of the intestinal tract are not clear. Here, we show that genetic deletion of TIPE in mice exacerbated chemical-induced colitis and colitis-associated colon cancer. Loss of TIPE exacerbated inflammatory responses and inflammation-associated dysbiosis, leading to the activation of NF-κB and STAT3, and it also accelerated dysplasia, DNA damage and proliferation of intestinal epithelial cells. We further show that colon microbiota were essential for increased tumor growth and progression in Tipe−/− mice. The tumor suppressive function of TIPE originated primarily from the non-hematopoietic compartment. Importantly, TIPE was downregulated in human colorectal cancers, and patients with low levels of Tipe mRNA were associated with reduced survival. These results indicate that TIPE serves as an important modulator of colitis and colitis-associated colon cancer.
Zoonotic origin of the human malaria parasite Plasmodium malariae from African apes
Authors: Plenderleith Lindsey J. , Liu Weimin , Li Yingying , Loy Dorothy E. , Mollison Ewan , Connell Jesse , Ayouba Ahidjo , Esteban Amandine , Peeters Martine , Sanz Crickette M. , Morgan David B. , Wolfe Nathan D. , Ulrich Markus , Sachse Andreas , Calvignac-Spencer Sébastien , Leendertz Fabian H. , Shaw George M. , Hahn Beatrice H. , Sharp Paul M. 
Published: April 2022

AbstractThe human parasite Plasmodium malariae has relatives infecting African apes (Plasmodium rodhaini) and New World monkeys (Plasmodium brasilianum), but its origins remain unknown. Using a novel approach to characterise P. malariae-related sequences in wild and captive African apes, we found that this group comprises three distinct lineages, one of which represents a previously unknown, highly divergent species infecting chimpanzees, bonobos and gorillas across central Africa. A second ape-derived lineage is much more closely related to the third, human-infective lineage P. malariae, but exhibits little evidence of genetic exchange with it, and so likely represents a separate species. Moreover, the levels and nature of genetic polymorphisms in P. malariae indicate that it resulted from the zoonotic transmission of an African ape parasite, reminiscent of the origin of P. falciparum. In contrast, P. brasilianum falls within the radiation of human P. malariae, and thus reflects a recent anthroponosis.
DNA sequence-dependent formation of heterochromatin nanodomains
Authors: Thorn Graeme J. , Clarkson Christopher T. , Rademacher Anne , Mamayusupova Hulkar , Schotta Gunnar , Rippe Karsten , Teif Vladimir B. 
Published: April 2022

AbstractThe mammalian epigenome contains thousands of heterochromatin nanodomains (HNDs) marked by di- and trimethylation of histone H3 at lysine 9 (H3K9me2/3), which have a typical size of 3–10 nucleosomes. However, what governs HND location and extension is only partly understood. Here, we address this issue by introducing the chromatin hierarchical lattice framework (ChromHL) that predicts chromatin state patterns with single-nucleotide resolution. ChromHL is applied to analyse four HND types in mouse embryonic stem cells that are defined by histone methylases SUV39H1/2 or GLP, transcription factor ADNP or chromatin remodeller ATRX. We find that HND patterns can be computed from PAX3/9, ADNP and LINE1 sequence motifs as nucleation sites and boundaries that are determined by DNA sequence (e.g. CTCF binding sites), cooperative interactions between nucleosomes as well as nucleosome-HP1 interactions. Thus, ChromHL rationalizes how patterns of H3K9me2/3 are established and changed via the activity of protein factors in processes like cell differentiation.
Open-channel microfluidics via resonant wireless power transfer
Authors: Ertsgaard Christopher T. , Yoo Daehan , Christenson Peter R. , Klemme Daniel J. , Oh Sang-Hyun 
Published: April 2022

AbstractOpen-channel microfluidics enables precise positioning and confinement of liquid volume to interface with tightly integrated optics, sensors, and circuit elements. Active actuation via electric fields can offer a reduced footprint compared to passive microfluidic ensembles and removes the burden of intricate mechanical assembly of enclosed systems. Typical systems actuate via manipulating surface wettability (i.e., electrowetting), which can render low-voltage but forfeits open-microchannel confinement. The dielectric polarization force is an alternative which can generate open liquid microchannels (sub-100 µm) but requires large operating voltages (50–200 VRMS) and low conductivity solutions. Here we show actuation of microchannels as narrow as 1 µm using voltages as low as 0.5 VRMS for both deionized water and physiological buffer. This was achieved using resonant, nanoscale focusing of radio frequency power and an electrode geometry designed to abate surface tension. We demonstrate practical fluidic applications including open mixing, lateral-flow protein labeling, filtration, and viral transport for infrared biosensing—known to suffer strong absorption losses from enclosed channel material and water. This tube-free system is coupled with resonant wireless power transfer to remove all obstructing hardware — ideal for high-numerical-aperture microscopy. Wireless, smartphone-driven fluidics is presented to fully showcase the practical application of this technology.
Enhancement of prime editing via xrRNA motif-joined pegRNA
Authors: Zhang Guiquan , Liu Yao , Huang Shisheng , Qu Shiyuan , Cheng Daolin , Yao Yuan , Ji Quanjiang , Wang Xiaolong , Huang Xingxu , Liu Jianghuai 
Published: April 2022

AbstractThe prime editors (PEs) have shown great promise for precise genome modification. However, their suboptimal efficiencies present a significant technical challenge. Here, by appending a viral exoribonuclease-resistant RNA motif (xrRNA) to the 3′-extended portion of pegRNAs for their increased resistance against degradation, we develop an upgraded PE platform (xrPE) with substantially enhanced editing efficiencies in multiple cell lines. A pan-target average enhancement of up to 3.1-, 4.5- and 2.5-fold in given cell types is observed for base conversions, small deletions, and small insertions, respectively. Additionally, xrPE exhibits comparable edit:indel ratios and similarly minimal off-target editing as the canonical PE3. Of note, parallel comparison of xrPE to the most recently developed epegRNA-based PE system shows their largely equivalent editing performances. Our study establishes a highly adaptable platform of improved PE that shall have broad implications.