bluuebunny/crossref_metadata_2025 huggingface dataset:
Credibility, transparency, and sustainability in fashion: a game-theoretic perspective
Authors: Nandkeolyar Olivia , Chen Frederick
Published: December 2022

We present a game-theoretic model of a firm’s production decision to analyze the conditions under which the firm would engage in sustainable practices when there exists a certification agency that can audit the firm. Our results show that when the certification agency is firm-owned or when it is an independent, profit-maximizing entity, then there is no equilibrium in which the firm chooses to produce in a sustainable manner. We also present real-world examples from the apparel and footwear industry, as well as the mining industry, that are consistent with our theoretical results. We consider what would happen if the certification agency is government-operated or a non-profit organization with a mandate to monitor the firm’s production process. We show that – combined with tax incentives or subsidies for the firm if necessary, and greater specificity regarding what is sustainable – there exists an equilibrium in which the firm would choose to engage in sustainable production in this case. We analyze extensions of the model to examine conditions under which the phenomenon of greenwashing can arise as an equilibrium outcome. We also propose a “bounty system” that the government can implement to incentivize monitoring of firms’ production processes, and we show how such a policy can induce more sustainable production practices by the firm.
ISOMORPHISM OF LOCALLY COMPACT POLISH METRIC STRUCTURES
Authors: MALICKI MACIEJ
Published: December 2022

We study the isomorphism relation on Borel classes of locally compact Polish metric structures. We prove that isomorphism on such classes is always classifiable by countable structures (equivalently: Borel reducible to graph isomorphism), which implies, in particular, that isometry of locally compact Polish metric spaces is Borel reducible to graph isomorphism. We show that potentially
$\boldsymbol {\Pi }^{0}_{\alpha + 1}$
isomorphism relations are Borel reducible to equality on hereditarily countable sets of rank
$\alpha $
,
$\alpha \geq 2$
. We also study approximations of the Hjorth-isomorphism game, and formulate a condition ruling out classifiability by countable structures.
La estructura del cenáculo: Las redes intelectuales ante la literatura latinoamericana
Authors: Rodríguez-Alfonso Adriana
Published: December 2022

El siguiente artículo analiza el estado actual de la perspectiva de redes intelectuales, especialmente en el cruce con los estudios literarios en América Latina. Partiendo de sus primeros trabajos, discute las mentadasestabilidadytransdisciplinariedaddel campo de estudio, proponiendo un corpus de referencia para las estructuras de sociabilidad literaria. Posteriormente, el artículo revisa críticamente los tópicos, métodos y restricciones, así como las actuales indeterminaciones conceptuales y metodológicas, que sugieren que este es aún un campo en construcción. Finalmente, se proponen algunas ideas novedosas que podrían contribuir al desarrollo interdisciplinario del campo, extendiendo las potencialidades y ventajas de esta perspectiva a los estudios de literatura latinoamericana.
Landscape response to hydroclimate variability shown by the post-Bonneville Flood (ca. 18 ka) fluvial-geomorphic history of the middle Snake River, Idaho, USA
Authors: Bacon Steven N. , Bullard Thomas F. , Kimball Vaughn , Neudorf Christina M. , Baker Shane A.
Published: December 2022

The fluvial geomorphology and stratigraphy on the middle Snake River at Bancroft Springs, Idaho, provide evidence for numerous episodes of Snake River aggradation and incision since the Bonneville Flood at ca. 18 ka. A suite of seven terraces ranging from 20–1 m above modern bankfull elevation records multiple cut-and-fill cycles during the latest Pleistocene and Holocene in response to local base-level controls, variations in sediment supply, and hydroclimate change. Radiocarbon and luminescence dating show that the ages of fluvial aggradation generally coincide with increased sediment supply and likely wetter hydroclimate during onset of the Younger Dryas stadial (ca. 13.2 ka), deglaciation and termination of the Younger Dryas stadial (ca. 11.3 ka), Early Holocene cooling (ca. 8.8 ka), and Neoglacial (ca. 4.5, 2.9, 1.1 ka). Six intervening periods of incision and channel stability may also reflect either reduced sediment supply, drier hydroclimate, or both. The terrace chronology can be correlated to a variety of local and regional paleoclimate proxy records and corresponds well with periods of continental- and global-scale rapid climate change during the Holocene. The fluvial record demonstrates the geomorphic response and sensitivity of large river systems to changes in hydroclimate variability, which has important implications for inferring paleoenvironmental conditions in the region.
Philip Kerr, Berlin Noir, and the (Problematic) Representation of History
Authors: Berberich Christine
Published: December 2022

The private eye Bernie Günther investigates the gruesome deaths of a prominent Berlin businessman's daughter and son-in-law in a house fire. The backdrop is Nazi Germany in the run up to the Berlin Olympics that took place between August 1 and 16, 1936 and that Hitler actively manipulated to present a somewhat whitewashed image of Nazi Germany to the world.
Nanoformulation approach for improved antimicrobial activity of bovine lactoperoxidase
Authors: Singh Anamika , Singh Jiya , Singh Tej P. , Sharma Pradeep , Sharma Sujata
Published: December 2022

Lactoperoxidase (LPO) is a glycosylated antimicrobial protein present in milk with a molecular mass of 78 kDa. LPO is included in many biological processes and is well-known to have biocidal actions, acting as an active antibiotic and antiviral agent. The wide spectrum biocidal activity of LPO is mediated via a definite inhibitory system named lactoperoxidase system which plays a potent role in the innate immune response. With the current advancement in nanotechnology, nanoformulations can be developed for stabilizing and potentiating the activity of LPO for several applications. In the research described in this Research Communication, fresh LPO purified from bovine mammary gland secretions was used for nanoparticle synthesis using a simple thermal process at different pH and temperatures. The round-shaped nanoparticles (average size 229 nm) were successfully synthesized at pH 7.0 and a temperature of 75°C. These nanoparticles were tested against four different bacterial species namely S. flexineri, P. aeruginosa, S. aureus, and E. coli. The prepared nanoparticles exhibited strong inhibition of the growth against all four bacterial species as stated by their MIC and ZOI values. These results may help in increasing the efficiency of lactoperoxidase system and will assist in identifying novel avenues to enhance the stability and antimicrobial function of LPO in drug discovery and industrial processes.
La isla de Atitlán: un nuevo yacimiento de obsidiana en el Occidente de México
Authors: Blanco Morales Ericka Sofía , Acosta Ochoa Guillermo , Esparza López Rodrigo
Published: December 2022

Durante la época prehispánica, la obsidiana se caracterizó por ser una materia prima de primera necesidad para la elaboración de gran variedad de objetos. La tecnología de talla para la extracción de diversos artefactos fue una importante actividad económica. En el occidente de México, la obsidiana resultó un recurso fundamental debido a su abundancia y a la diversidad de yacimientos presentes. Sin embargo, no todos los vidrios volcánicos disponibles tienen las características idóneas para la talla especializada. En la región Valles, dentro de las cuencas centrales del estado de Jalisco, se encuentran dispersos nódulos de obsidiana, con un alto grado de inclusiones, que ha sido referida meramente como “obsidiana de baja calidad”. Hasta ahora, en pocas ocasiones se le ha dado la importancia debida en cuanto al estudio de su composición geoquímica, a pesar de que este sirva para contrastarlo con aquellas que sí fueron empleadas como materia prima. El siguiente trabajo busca establecer las características de la obsidiana disponible en el sitio Atitlán, ubicado en la antigua Cuenca de Magdalena, para compararla con los desechos de un espacio en el que son evidentes talleres especializados de talla intensiva para la extracción de láminas que sirvieron para elaborar piezas útiles. Entre los objetivos primordiales del artículo, es comparar sus particularidades con las de la obsidiana empleada en el proceso productivo proveniente del sitio La Joya. Gracias a esta investigación, demostramos que la obsidiana disponible en la isla no fue aprovechada debido al tamaño de los nódulos disponibles y al alto grado de porosidad e inclusiones.
“The Most Extraordinary Novel of Modern Times”: Collaborative Fiction in The Gentlewoman
Authors: Bilston Sarah
Published: December 2022

This article investigates two collaborative (and little-known) novels published in the early 1890s periodical The Gentlewoman. The collaborations turn on, and center, a heroine whose reputation, choices, and actions stand as the locus of investigation; the business of interpreting a woman's character brings multiple writers, from many walks of life, together in a shared enterprise shaped by ongoing disagreement, for how to interpret the heroine evolves week by week. The two texts disrupt not only their own reading of their heroine but stage, through their very form, that any fixed, stable, or unitary reading of womanhood is impossible.
Liubai Technique in the Real-time Electroacoustic Chinese Art Song ‘Lang Tao Sha’ (浪淘沙)
Authors: Mengchun Yang , Zhixin Xu
Published: December 2022

Liubai(留白, literally ‘leaving blankness’) is a unique method of expression in Chinese classical paintings. The core spirit of the technique is inextricably linked to ancient Chinese Taoism and traditional aesthetics, which are prominently featured by simplicity and nationality. This article, taking the real-time interactive electroacoustic Chinese art song ‘Lang Tao Sha’ (浪淘沙), explores the use of the artistic technique ofliubaifrom the perspective of a soprano singer by focusing on the three aspects of lyrics, vocal music and electroacoustic music creation, and singing performance.
DNA methylation and gene expression analysis in adipose tissue to identify new loci associated with T2D development in obesity
Authors: Baca Paulina , Barajas-Olmos Francisco , Mirzaeicheshmeh Elaheh , Zerrweck Carlos , Guilbert Lizbeth , Sánchez Ernesto Carlos , Flores-Huacuja Marlen , Villafán Rafael , Martínez-Hernández Angélica , García-Ortiz Humberto , Contreras-Cubas Cecilia , Centeno-Cruz Federico , Orozco Lorena
Published: December 2022

Background

Obesity is accompanied by excess adipose fat storage, which may lead to adipose dysfunction, insulin resistance, and type 2 diabetes (T2D). Currently, the tendency to develop T2D in obesity cannot be explained by genetic variation alone—epigenetic mechanisms, such as DNA methylation, might be involved. Here, we aimed to identify changes in DNA methylation and gene expression in visceral adipose tissue (VAT) that might underlie T2D susceptibility in patients with obesity.

Methods

We investigated DNA methylation and gene expression in VAT biopsies from 19 women with obesity, without (OND = 9) or with T2D (OD = 10). Differences in genome-scale methylation (differentially methylated CpGs [DMCs], false discovery rate < 0.05; and differentially methylated regions [DMRs],pvalue < 0.05) and gene expression (DEGs,pvalue <0.05) between groups were assessed. We searched for overlap between altered methylation and expression and the impact of altered DNA methylation on gene expression, using bootstrap Pearson correlation. The relationship of altered DNA methylation to T2D-related traits was also tested.

Results

We identified 11 120 DMCs and 96 DMRs distributed across all chromosomes, with the greatest density of epigenomic alterations at the MHC locus. These alterations were found in newly and previously T2D-related genes. Several of these findings were supported by validation and extended multi-ethnic analyses. Of 252 DEGs in the OD group, 68 genes contained DMCs (n = 88), of which 24 demonstrated a significant relationship between gene expression and methylation (pvalues <0.05). Of these, 16, includingATP11A,LPLandEHD2also showed a significant correlation with fasting glucose and HbA1c levels.

Conclusions

Our results revealed novel candidate genes related to T2D pathogenesis in obesity. These genes show perturbations in DNA methylation and expression profiles in patients with obesity and diabetes. Methylation profiles were able to discriminate OND from OD individuals; DNA methylation is thus a potential biomarker.
Venetoclax with decitabine versus decitabine monotherapy in elderly acute myeloid leukemia: a propensity score-matched analysis
Authors: Kwag Daehun , Cho Byung-Sik , Bang Su-Yeon , Lee Jong Hyuk , Min Gi-June , Park Sung-Soo , Park Silvia , Yoon Jae-Ho , Lee Sung-Eun , Eom Ki-Seong , Kim Yoo-Jin , Lee Seok , Min Chang-Ki , Cho Seok-Goo , Lee Jong Wook , Kim Hee-Je
Published: December 2022

Venetoclax (VEN) combined with azacitidine (AZA) or decitabine (DEC) has been approved for older adults with acute myeloid leukemia (AML) unfit for intensive chemotherapy based on the pivotal VIALE-A trial. However, this trial only compared AZA + VEN with AZA monotherapy. Therefore, we compared the outcomes of consecutive older adults (65 years or older) with newly diagnosed AML who received DEC (n = 230) or DEC + VEN (n = 74) after propensity score matching to construct a one-to-one matched cohort by the nearest neighbor algorithm. The median overall survival was longer in the DEC + VEN group than in the DEC group (13.4 months vs. 8.3 months, p = 0.01). The median event-free survivals were 8.6 and 5.8 months in the DEC + VEN and DEC groups, respectively (p = 0.02). The response rate (complete response, complete response with incomplete hematologic recovery, and morphologic leukemia-free state) was significantly higher in the DEC + VEN group than in the DEC group (70.3% vs. 24.3%, p < 0.01). The 30-day (2.7% vs. 9.5%, p = 0.17) and 60-day (9.5% vs. 18.9%, p = 0.16) mortality rates did not differ between the two groups, nor did the median hospitalization and transfusion rates (hospitalization: 23 days vs. 21 days, p = 0.20; red blood cells: 3.2 units/month vs. 3.5 units/month, p = 0.73; platelets: 2.7 units/month vs. 2.3 units/months, p = 0.48). Of those who received DEC + VEN and became leukemia-free, 29% underwent allogeneic stem cell transplantation and had excellent survival outcomes (one-year survival: 79.4%; one-year non-relapse mortality: 13.3%). This study is the first to provide real-world evidence that DEC + VEN has superior outcomes to DEC monotherapy.
Endoplasmic reticulum stress-mediated cell death in liver injury
Authors: Zhang Jian , Guo Jiafu , Yang Nannan , Huang Yan , Hu Tingting , Rao Chaolong
Published: December 2022

The endoplasmic reticulum is an important intracellular organelle that plays an important role in maintaining cellular homeostasis. Endoplasmic reticulum stress (ERS) and unfolded protein response (UPR) are induced when the body is exposed to adverse external stimuli. It has been established that ERS can induce different cell death modes, including autophagy, apoptosis, ferroptosis, and pyroptosis, through three major transmembrane receptors on the ER membrane, including inositol requirement enzyme 1α, protein kinase-like endoplasmic reticulum kinase and activating transcription factor 6. These different modes of cell death play an important role in the occurrence and development of various diseases, such as neurodegenerative diseases, inflammation, metabolic diseases, and liver injury. As the largest metabolic organ, the liver is rich in enzymes, carries out different functions such as metabolism and secretion, and is the body’s main site of protein synthesis. Accordingly, a well-developed endoplasmic reticulum system is present in hepatocytes to help the liver perform its physiological functions. Current evidence suggests that ERS is closely related to different stages of liver injury, and the death of hepatocytes caused by ERS may be key in liver injury. In addition, an increasing body of evidence suggests that modulating ERS has great potential for treating the liver injury. This article provided a comprehensive overview of the relationship between ERS and four types of cell death. Moreover, we discussed the mechanism of ERS and UPR in different liver injuries and their potential therapeutic strategies.
A comparison of the genes and genesets identified by GWAS and EWAS of fifteen complex traits
Authors: Battram Thomas , Gaunt Tom R. , Relton Caroline L. , Timpson Nicholas J. , Hemani Gibran
Published: December 2022

Identifying genomic regions pertinent to complex traits is a common goal of genome-wide and epigenome-wide association studies (GWAS and EWAS). GWAS identify causal genetic variants, directly or via linkage disequilibrium, and EWAS identify variation in DNA methylation associated with a trait. While GWAS in principle will only detect variants due to causal genes, EWAS can also identify genes via confounding, or reverse causation. We systematically compare GWAS (N > 50,000) and EWAS (N > 4500) results of 15 complex traits. We evaluate if the genes or gene ontology terms flagged by GWAS and EWAS overlap, and find substantial overlap for diastolic blood pressure, (gene overlap P = 5.2 × 10−6; term overlap P = 0.001). We superimpose our empirical findings against simulated models of varying genetic and epigenetic architectures and observe that in most cases GWAS and EWAS are likely capturing distinct genesets. Our results indicate that GWAS and EWAS are capturing different aspects of the biology of complex traits.
Shining light on the microscopic resonant mechanism responsible for cavity-mediated chemical reactivity
Authors: Schäfer Christian , Flick Johannes , Ronca Enrico , Narang Prineha , Rubio Angel
Published: December 2022

Strong light–matter interaction in cavity environments is emerging as a promising approach to control chemical reactions in a non-intrusive and efficient manner. The underlying mechanism that distinguishes between steering, accelerating, or decelerating a chemical reaction has, however, remained unclear, hampering progress in this frontier area of research. We leverage quantum-electrodynamical density-functional theory to unveil the microscopic mechanism behind the experimentally observed reduced reaction rate under cavity induced resonant vibrational strong light-matter coupling. We observe multiple resonances and obtain the thus far theoretically elusive but experimentally critical resonant feature for a single strongly coupled molecule undergoing the reaction. While we describe only a single mode and do not explicitly account for collective coupling or intermolecular interactions, the qualitative agreement with experimental measurements suggests that our conclusions can be largely abstracted towards the experimental realization. Specifically, we find that the cavity mode acts as mediator between different vibrational modes. In effect, vibrational energy localized in single bonds that are critical for the reaction is redistributed differently which ultimately inhibits the reaction.
Wood structure explained by complex spatial source-sink interactions
Authors: Friend Andrew D. , Eckes-Shephard Annemarie H. , Tupker Quinten
Published: December 2022

Wood is a remarkable material with great cultural, economic, and biogeochemical importance. However, our understanding of its formation is poor. Key properties that have not been explained include the anatomy of growth rings (with consistent transitions from low-density earlywood to high density latewood), strong temperature-dependence of latewood density (used for historical temperature reconstructions), the regulation of cell size, and overall growth-temperature relationships in conifer and ring-porous tree species. We have developed a theoretical framework based on observations on Pinus sylvestris L. in northern Sweden. The observed anatomical properties emerge from our framework as a consequence of interactions in time and space between the production of new cells, the dynamics of developmental zone widths, and the distribution of carbohydrates across the developing wood. Here we find that the diffusion of carbohydrates is critical to determining final ring anatomy, potentially overturning current understanding of how wood formation responds to environmental variability and transforming our interpretation of tree rings as proxies of past climates.
Torsional periodic lattice distortions and diffraction of twisted 2D materials
Authors: Sung Suk Hyun , Goh Yin Min , Yoo Hyobin , Engelke Rebecca , Xie Hongchao , Zhang Kuan , Li Zidong , Ye Andrew , Deotare Parag B. , Tadmor Ellad B. , Mannix Andrew J. , Park Jiwoong , Zhao Liuyan , Kim Philip , Hovden Robert
Published: December 2022

Twisted 2D materials form complex moiré structures that spontaneously reduce symmetry through picoscale deformation within a mesoscale lattice. We show twisted 2D materials contain a torsional displacement field comprised of three transverse periodic lattice distortions (PLD). The torsional PLD amplitude provides a single order parameter that concisely describes the structural complexity of twisted bilayer moirés. Moreover, the structure and amplitude of a torsional periodic lattice distortion is quantifiable using rudimentary electron diffraction methods sensitive to reciprocal space. In twisted bilayer graphene, the torsional PLD begins to form at angles below 3.89° and the amplitude reaches 8 pm around the magic angle of 1. 1°. At extremely low twist angles (e.g. below 0.25°) the amplitude increases and additional PLD harmonics arise to expand Bernal stacked domains separated by well defined solitonic boundaries. The torsional distortion field in twisted bilayer graphene is analytically described and has an upper bound of 22.6 pm. Similar torsional distortions are observed in twisted WS2, CrI3, and WSe2/MoSe2.
Groundwater depletion in California’s Central Valley accelerates during megadrought
Authors: Liu Pang-Wei , Famiglietti James S. , Purdy Adam J. , Adams Kyra H. , McEvoy Avery L. , Reager John T. , Bindlish Rajat , Wiese David N. , David Cédric H. , Rodell Matthew
Published: December 2022

Groundwater provides nearly half of irrigation water supply, and it enables resilience during drought, but in many regions of the world, it remains poorly, if at all managed. In heavily agricultural regions like California’s Central Valley, where groundwater management is being slowly implemented over a 27-year period that began in 2015, groundwater provides two–thirds or more of irrigation water during drought, which has led to falling water tables, drying wells, subsiding land, and its long-term disappearance. Here we use nearly two decades of observations from NASA’s GRACE satellite missions and show that the rate of groundwater depletion in the Central Valley has been accelerating since 2003 (1.86 km3/yr, 1961–2021; 2.41 km3/yr, 2003–2021; 8.58 km3/yr, 2019–2021), a period of megadrought in southwestern North America. Results suggest the need for expedited implementation of groundwater management in the Central Valley to ensure its availability during the increasingly intense droughts of the future.
Constructing high-efficiency orange-red thermally activated delayed fluorescence emitters by three-dimension molecular engineering
Authors: Hua Lei , Liu Yuchao , Liu Binbin , Zhao Zhennan , Zhang Lei , Yan Shouke , Ren Zhongjie
Published: December 2022

Preparing high-efficiency solution-processable orange-red thermally activated delayed fluorescence (TADF) emitters remains challenging. Herein, we design a series of emitters consisting of trinaphtho[3,3,3]propellane (TNP) core derivatized with different TADF units. Benefiting from the unique hexagonal stacking architecture of TNPs, TADF units are thus kept in the cavities between two TNPs, which decrease concentration quenching and annihilation of long-lived triplet excitons. According to the molecular engineering of TADF and host units, the excited states can further be regulated to effectively enhance spin-orbit coupling (SOC) processes. We observe a high-efficiency orange-red emission at 604 nm in one instance with high SOC value of 0.862 cm−1and high photoluminescence quantum yield of 70.9%. Solution-processable organic light-emitting diodes exhibit a maximum external quantum efficiency of 24.74%. This study provides a universal strategy for designing high-performance TADF emitters through molecular packing and excited state regulation.
Genomic heterogeneity in pancreatic cancer organoids and its stability with culture
Authors: Usman Olalekan H. , Zhang Liting , Xie Gengqiang , Kocher Hemant M. , Hwang Chang-il , Wang Yue Julia , Mallory Xian , Irianto Jerome
Published: December 2022

The establishment of patient-derived pancreatic cancer organoid culture in recent years creates an exciting opportunity for researchers to perform a wide range of in vitro studies on a model that closely recapitulates the tumor. One of the outstanding question in pancreatic cancer biology is the causes and consequences of genomic heterogeneity observed in the disease. However, to use pancreatic cancer organoids as a model to study genomic variations, we need to first understand the degree of genomic heterogeneity and its stability within organoids. Here, we used single-cell whole-genome sequencing to investigate the genomic heterogeneity of two independent pancreatic cancer organoid lines, as well as their genomic stability with extended culture. Clonal populations with similar copy number profiles were observed within the organoids, and the proportion of these clones was shifted with extended culture, suggesting the growth advantage of some clones. However, sub-clonal genomic heterogeneity was also observed within each clonal population, indicating the genomic instability of the pancreatic cancer cells themselves. Furthermore, our transcriptomic analysis also revealed a positive correlation between copy number alterations and gene expression regulation, suggesting the “gene dosage” effect of these copy number alterations that translates to gene expression regulation.
Quantum-enhanced Doppler lidar
Authors: Reichert Maximilian , Di Candia Roberto , Win Moe Z. , Sanz Mikel
Published: December 2022

We propose a quantum-enhanced lidar system to estimate a target’s radial velocity, which employs squeezed and frequency-entangled signal and idler beams. We compare its performance against a classical protocol using a coherent state with the same pulse duration and energy, showing that quantum resources provide a precision enhancement in the estimation of the velocity of the object. We identify three distinct parameter regimes characterized by the amount of squeezing and frequency entanglement. In two of them, a quantum advantage exceeding the standard quantum limit is achieved assuming no photon losses. Additionally, we show that an optimal measurement to attain these results in the lossless case is frequency-resolved photon counting. Finally, we consider the effect of photon losses for the high-squeezing regime, which leads to a constant factor quantum advantage higher than 3 dB in the variance of the estimator, given a roundtrip lidar-to-target-to-lidar transmissivity larger than 50%.
Majorana modes with side features in magnet-superconductor hybrid systems
Authors: Crawford Daniel , Mascot Eric , Shimizu Makoto , Beck Philip , Wiebe Jens , Wiesendanger Roland , Jeschke Harald O. , Morr Dirk K. , Rachel Stephan
Published: December 2022

Magnet-superconductor hybrid (MSH) systems represent promising platforms to host Majorana zero modes (MZMs), the elemental building blocks for fault-tolerant quantum computers. Theoretical description of such MSH structures is mostly based on simplified models, not accounting for the complexity of real materials. Here, based on density functional theory, we derive a superconducting 80-band model to study an MSH system consisting of a magnetic manganese chain on the s wave superconductor niobium. For a wide range of values of the superconducting order parameter, the system is a topological superconductor, with MZMs exhibiting non-universal spatial patterns and a drastic accumulation of spectral weight on both sides along the magnetic chain. These side feature states can be explained by an effective model which is guided by the ab initio results. Performing scanning tunneling spectroscopy experiments on the same system, we observe a spatial structure in the low-energy local density of states that is consistent with the theoretical findings. Our results open a first-principle approach to the discovery of topological superconductors.
Oxygen isotope evidence from Ryugu samples for early water delivery to Earth by CI chondrites
Authors: Greenwood Richard C. , Franchi Ian A. , Findlay Ross , Malley James A. , Ito Motoo , Yamaguchi Akira , Kimura Makoto , Tomioka Naotaka , Uesugi Masayuki , Imae Naoya , Shirai Naoki , Ohigashi Takuji , Liu Ming-Chang , McCain Kaitlyn A. , Matsuda Nozomi , McKeegan Kevin D. , Uesugi Kentaro , Nakato Aiko , Yogata Kasumi , Yuzawa Hayato , Kodama Yu , Tsuchiyama Akira , Yasutake Masahiro , Hirahara Kaori , Tekeuchi Akihisa , Sekimoto Shun , Sakurai Ikuya , Okada Ikuo , Karouji Yuzuru , Nakazawa Satoru , Okada Tatsuaki , Saiki Takanao , Tanaka Satoshi , Terui Fuyuto , Yoshikawa Makoto , Miyazaki Akiko , Nishimura Masahiro , Yada Toru , Abe Masanao , Usui Tomohiro , Watanabe Sei-ichiro , Tsuda Yuichi
Published: December 2022

The delivery of water to the inner Solar System, including Earth, is still a debated topic. A preferential role for hydrated asteroids in this process is supported by isotopic measurements. Carbonaceous chondrite (CC) meteorites represent our main source of information about these volatile-rich asteroids. However, the destruction of weaker materials during atmospheric entry creates a bias in our CC data. The return of surface materials from the C-type asteroid 162173 Ryugu by the Hayabusa2 spacecraft provides a unique opportunity to study high-porosity, low-density, primitive materials, unrepresented in the meteorite record. We measured the bulk oxygen isotope composition from four Ryugu particles and show that they most closely resemble the rare CI (CC Ivuna-type) chondrites, but with some differences that we attribute to the terrestrial contamination of the CI meteorites. We suggest that CI-related material is widespread among carbonaceous asteroids and a more important source of Earth’s water and other volatiles than its limited presence in our meteoritic collection indicates.
Quantitative tissue perfusion imaging using nonlinear ultrasound localization microscopy
Authors: Harmon Jennifer N. , Khaing Zin Z. , Hyde Jeffrey E. , Hofstetter Christoph P. , Tremblay-Darveau Charles , Bruce Matthew F.
Published: December 2022

Ultrasound localization microscopy (ULM) is a recent advancement in ultrasound imaging that uses microbubble contrast agents to yield vascular images that break the classical diffraction limit on spatial resolution. Current approaches cannot image blood flow at the tissue perfusion level since they rely solely on differences in velocity to separate tissue and microbubble signals; lower velocity microbubble echoes are removed during high pass wall filtering. To visualize blood flow in the entire vascular tree, we have developed nonlinear ULM, which combines nonlinear pulsing sequences with plane-wave imaging to segment microbubble signals independent of their velocity. Bubble localization and inter-frame tracking produces super-resolved images and, with parameters derived from the bubble tracks, a rich quantitative feature set that can describe the relative quality of microcirculatory flow. Using the rat spinal cord as a model system, we showed that nonlinear ULM better resolves some smaller branching vasculature compared to conventional ULM. Following contusion injury, both gold-standard histological techniques and nonlinear ULM depicted reduced in-plane vessel length between the penumbra and contralateral gray matter (−16.7% vs. −20.5%, respectively). Here, we demonstrate that nonlinear ULM uniquely enables investigation and potential quantification of tissue perfusion, arguably the most important component of blood flow.
Meta-analytic evidence for a sex-diverging association between alcohol use and body mass index
Authors: Siegmann Eva-Maria , Mazza Massimiliano , Weinland Christian , Kiefer Falk , Kornhuber Johannes , Mühle Christiane , Lenz Bernd
Published: December 2022

Alcohol use is an important health issue and has been suggested to contribute to the burden produced by obesity. Both alcohol use and obesity are subject to sex differences. The available studies on the relationship between alcohol use and body mass index (BMI) report inconsistent results with positive, negative, and null findings which requests a meta-analytic approach. Therefore, we conducted a meta-analysis of case–control, cohort, and cross-sectional studies. The systematic literature search and data extraction was performed by 3 independent raters. We conducted sex-separated meta-analyses and -regressions to investigate how alcohol consumption associates with BMI. Our systematic literature search resulted in 36 studies with 48 data sets (Nmen = 172,254; kmen = 30; Nwomen = 24,164; kwomen = 18; Nunknown sex = 672,344; kunknown sex = 24). Alcohol use was associated with higher BMI in men (g = 0.08 [0.07; 0.09]) and lower BMI in women (g = − 0.26 [− 0.29; − 0.22]). Moreover, we found the amount of daily alcohol intake in men (β = 0.001 [0.0008; 0.0014]) and ethnicity in women (g[Caucasians] = − 0.45 versus g[Asians] = − 0.05; z = 11.5, p < 0.0001) to moderate these effects. We here identified sex-diverging relationships between alcohol use and BMI, found daily alcohol intake and ethnicity to sex-specifically moderate these effects, and argue that sex-specific choice of beverage type and higher amount of daily alcohol use in men than in women account for these observations. Future research is needed to provide empirical evidence for the underlying mechanisms.
Toxicity of extracellular alpha-synuclein is independent of intracellular alpha-synuclein
Authors: Dening Yanina , Straßl Theresa , Ruf Viktoria , Dirscherl Petra , Chovsepian Alexandra , Stievenard Alicia , Khairnar Amit , Schmidt Felix , Giesert Florian , Herms Jochen , Levin Johannes , Dieterich Marianne , Falkai Peter , Weisenhorn Daniela Vogt , Wurst Wolfgang , Giese Armin , Pan-Montojo Francisco
Published: December 2022

Parkinson´s disease (PD) pathology progresses throughout the nervous system. Whereas motor symptoms are always present, there is a high variability in the prevalence of non-motor symptoms. It has been postulated that the progression of the pathology is based on a prion-like disease mechanism partly due to the seeding effect of endocytosed-alpha-synuclein (ASYN) on the endogenous ASYN. Here, we analyzed the role of endogenous ASYN in the progression of PD-like pathology in vivo and in vitro and compared the effect of endocytosed-ASYN as well as paraquat and rotenone on primary enteric, dopaminergic and cortical neurons from wild-type and ASYN-KO mice. Our results show that, in vivo, pathology progression did not occur in the absence of endogenous ASYN. Remarkably, the damage caused by endocytosed-ASYN, rotenone or paraquat was independent from endogenous ASYN and related to the alteration of the host´s mitochondrial membrane potential. Dopaminergic neurons were very sensitive to these noxae compared to other neuronal subtypes. These results suggest that ASYN-mitochondrial interactions play a major role in initiating the pathological process in the host neuron and endogenous ASYN is essential for the transsynaptical transmission of the pathology. Our results also suggest that protecting mitochondrial function is a valid primary therapeutic target.
Cardiovascular predictors of mortality and exacerbations in patients with COPD
Authors: Alter Peter , Lucke Tanja , Watz Henrik , Andreas Stefan , Kahnert Kathrin , Trudzinski Franziska C. , Speicher Tim , Söhler Sandra , Bals Robert , Waschki Benjamin , Welte Tobias , Rabe Klaus F. , Vestbo Jørgen , Wouters Emiel F. M. , Vogelmeier Claus F. , Jörres Rudolf A.
Published: December 2022

In chronic obstructive pulmonary disease (COPD), comorbidities and worse functional status predict worse outcomes, but how these predictors compare with regard to different outcomes is not well studied. We thus compared the role of cardiovascular comorbidities for mortality and exacerbations. Data from baseline and up to four follow-up visits of the COSYCONET cohort were used. Cox or Poisson regression was employed to determine the relationship of predictors to mortality or mean annual exacerbation rate, respectively. Predictors comprised major comorbidities (including cardiovascular disease), lung function (forced expiratory volume in 1 s [FEV1], diffusion capacity for carbon monoxide [TLCO]) and their changes over time, baseline symptoms, exacerbations, physical activity, and cardiovascular medication. Overall, 1817 patients were included. Chronic coronary artery disease (p = 0.005), hypertension (p = 0.044) and the annual decline in TLCO (p = 0.001), but not FEV1 decline, were predictors of mortality. In contrast, the annual decline of FEV1 (p = 0.019) but not that of TLCO or cardiovascular comorbidities were linked to annual exacerbation rate. In conclusion, the presence of chronic coronary artery disease and hypertension were predictors of increased mortality in COPD, but not of increased exacerbation risk. This emphasizes the need for broad diagnostic workup in COPD, including the assessment of cardiovascular comorbidity.

Clinical Trials: NCT01245933.
A bacterial virulence factor interacts with the splicing factor RBM5 and stimulates formation of nuclear RBM5 granules
Authors: Pourpre Renaud , Lakisic Goran , Desgranges Emma , Cossart Pascale , Pagliuso Alessandro , Bierne Hélène
Published: December 2022

L. monocytogenes causes listeriosis, a foodborne disease that is particularly dangerous for immunocompromised individuals and fetuses. Several virulence factors of this bacterial pathogen belong to a family of leucine-rich repeat (LRR)-containing proteins called internalins. Among these, InlP is known for its role in placental infection. We report here a function of InlP in mammalian cell nucleus organization. We demonstrate that bacteria do not produce InlP under in vitro culture conditions. When ectopically expressed in human cells, InlP translocates into the nucleus and changes the morphology of nuclear speckles, which are membrane-less organelles storing splicing factors. Using yeast two-hybrid screen, immunoprecipitation and pull-down experiments, we identify the tumor suppressor and splicing factor RBM5 as a major nuclear target of InlP. InlP inhibits RBM5-induced cell death and stimulate the formation of RBM5-induced nuclear granules, where the SC35 speckle protein redistributes. Taken together, these results suggest that InlP acts as a nucleomodulin controlling compartmentalization and function of RBM5 in the nucleus and that L. monocytogenes has developed a mechanism to target the host cell splicing machinery.
In vitro characterization of immune modulating drug-eluting immunobeads towards transarterial embolization in cancer
Authors: Negussie Ayele H. , Mikhail Andrew S. , Owen Joshua W. , Hong Natalie , Carlson Camella J. , Tang Yiqing , Carrow Kendal Paige , Mauda-Havakuk Michal , Lewis Andrew L. , Karanian John W. , Pritchard William F. , Wood Bradford J.
Published: December 2022

Hepatocellular carcinoma (HCC) is an aggressive liver cancer with limited effective treatment options. In this study, we selected TLR agonists imiquimod (IMQ), gardiquimod (GARD), GS-9620 and DSR 6434, and a small molecule checkpoint inhibitor, BMS-202, for characterization of drug loading and release from radiopaque embolic beads (DC Bead LUMI) for potential use in image-guided transarterial embolization (TACE) of HCC. The maximum drug loading capacity and amount of drug released over time were determined by high performance liquid chromatography and compared with the commonly used anthracycline, doxorubicin hydrochloride (Dox). Maximum drug loading was 204.54 ± 3.87, 65.97 ± 1.54, 65.95 ± 6.96, 65.28 ± 3.09, and 148.05 ± 2.24 mg of drug per milliliter of DC Bead LUMI for Dox, GARD, DSR 6434, IMQ, and BMS-202, respectively. Fast loading and subsequent rapid release in saline were observed for IMQ, GARD, and DSR 6434. These drugs could also be partially removed from the beads by repeated washing with de-ionized water suggesting weak interaction with the beads. Aggregation of IMQ was observed in water and saline. GS-9620 partially decomposed in the solubilizing solution, so loading and release were not characterized. Compared to TLR agonists, slower loading and release were observed for Dox and BMS-202. Potential factors influencing drug loading into and release from DC Bead LUMI including steric hinderance, hydrophobicity, drug pKa, and the electrostatic nature of the beads are discussed. The maximum loading capacity of BMS-202 and Dox in DC Bead LUMI exceeded the maximum theoretical loading capacity of the beads expected from ionic interaction alone suggesting additional drug-bead or drug-drug interactions may play a role. Slightly more release was observed for BMS-202 at early time points followed by a slower release compared to Dox. Further study of these drug-bead combinations is warranted in search of new tools for locoregional delivery of immune-modulating agents for treatment of HCC via drug-eluting bead chemoembolization.
An inclined tower crane suited to bridge tower construction
Authors: Zhang Kun , Wang Hui , Zhou Yong , Wang Kaiqiang , Fang Xiaolin , Chen Baiben , Mu Dongdong
Published: December 2022

A new type of tower crane which could transform its tower body is presented. The inclined tower crane body can be tilted at some angle, which suits the construction of buildings with inclined architectural outlines, especially for the construction of bridge towers. The working principle and the design of the critical components are presented, two adjustable anchorages could pull the tower body section beneath the top anchorage closer to the construction region, and the related section of the tower body could change from vertical to inclined, while the free section of the tower body remains vertical. Finite element analysis is performed to compare with the traditional tower crane, the difference of the reaction force of the top anchorage is minor. Kinematic and dynamic analysis is carried out to simulate the working process of tilting, mechanical and kinematic parameters of key parts are obtained. At last, the experiment of a full-scale tower crane which could tilt 6° is carried out, and the experimental data validate the feasibility of this new type of tower crane.
Associations of leptin and corticostriatal connectivity in bipolar disorder
Authors: Wei Shyh-Yuh , Tseng Huai-Hsuan , Chang Hui Hua , Chang Wei Hung , Yang Yen Kuang , Chen Po See
Published: December 2022

Bipolar disorder (BD) and metabolic disturbance represent a chronic state of low-grade inflammation and corticostriatal circuitry alterations. Herein, we aimed to investigate whether plasma leptin, an adipokine that plays a key role in the interplay of metabolism and inflammation, is associated with corticostriatal connectivity in patients with BD. Twenty-eight BD I patients, 36 BD II patients and 66 healthy controls were enrolled and completed the Hamilton Depression Rating Scale, the Young Mania Rating Scale, and the Recent Life Change Questionnaire. Fasting plasma leptin and C-reactive protein (CRP) levels were measured, and corticostriatal connectivity was examined using functional magnetic resonance imaging (fMRI). The relationships between leptin, CRP and body mass index (BMI) identified in the controls and BD II patients were absent in the BD I patients. We did not find a significant group difference in the leptin level; nevertheless, the negative correlation between leptin level and corticostriatal connectivity (ventrolateral prefrontal cortex and inferior temporal gyrus) observed in the healthy controls was absent in the BD patients. The disproportionate increase in leptin level with increasing BMI in BD indicated a potential inflammatory role of white adipose tissue in BD. Furthermore, higher CRP levels in BD I patients might induce leptin resistance. Collectively, our results implied vulnerability to inflammatory and metabolic diseases in patients with BD, especially BD I.
Low-energy shock wave therapy ameliorates ischemic-induced overactive bladder in a rat model
Authors: Kimura Shingo , Kawamorita Naoki , Kikuchi Yoku , Shindo Tomohiko , Ishizuka Yuichi , Satake Yohei , Sato Takuma , Izumi Hideaki , Yamashita Shinichi , Yasuda Satoshi , Shimokawa Hiroaki , Ito Akihiro
Published: December 2022

This study was to evaluate whether Low-energy shock wave therapy (LESW) improves ischemic-induced overactive bladder in rats and investigate its therapeutic mechanisms. Sixteen-week-old male Sprague–Dawley rats were divided into three groups: arterial injury (AI), AI with LESW (AI-SW), and control groups. LESW was irradiated in AI-SW during 20–23 weeks of age. At 24 weeks of age, conscious cystometry was performed (each n = 8). The voiding interval was shortened in AI (mean ± SEM: 5.1 ± 0.8 min) than in control (17.3 ± 3.0 min), whereas significant improvements were observed in AI-SW (14.9 ± 3.3 min). The bladder blood flow was significantly increased in AI-SW than in AI. Microarray analysis revealed higher gene expression of soluble guanylate cyclase (sGC) α1 and β1 in the bladder of AI-SW compared to AI. Protein expression of sGCα1 and sGCβ1 was higher in AI-SW and control groups than in AI. Cyclic guanosine monophosphate (cGMP) was elevated in AI-SW. As an early genetic response, vascular endothelial growth factor and CD31 were highly expressed 24 h after the first LESW. Suburothelial thinning observed in AI was restored in AI-SW. Activation of sGC-cGMP may play a therapeutic role of LESW in the functional recovery of the bladder.
Brunner syndrome caused by point mutation explained by multiscale simulation of enzyme reaction
Authors: Prah Alja , Pregeljc Domen , Stare Jernej , Mavri Janez
Published: December 2022

Brunner syndrome is a disorder characterized by intellectual disability and impulsive, aggressive behavior associated with deficient function of the monoamine oxidase A (MAO-A) enzyme. These symptoms (along with particularly high serotonin levels) have been reported in patients with two missense variants in MAO-A (p.R45W and p.E446K). Herein, we report molecular simulations of the rate-limiting step of MAO-A-catalyzed serotonin degradation for these variants. We found that the R45W mutation causes a 6000-fold slowdown of enzymatic function, whereas the E446K mutation causes a 450-fold reduction of serotonin degradation rate, both of which are practically equivalent to a gene knockout. In addition, we thoroughly compared the influence of enzyme electrostatics on the catalytic function of both the wild type MAO-A and the p.R45W variant relative to the wild type enzyme, revealing that the mutation represents a significant electrostatic perturbation that contributes to the barrier increase. Understanding genetic disorders is closely linked to understanding the associated chemical mechanisms, and our research represents a novel attempt to bridge the gap between clinical genetics and the underlying chemical physics.