bluuebunny/crossref_metadata_2025 huggingface dataset:
Identifying climate models based on their daily output using machine learning
Authors: Brunner Lukas , Sippel Sebastian
Published: July 2023

Climate models are primary tools for investigating processes in the climate system, projecting future changes, and informing decision makers. The latest generation of models provides increasingly complex and realistic representations of the real climate system, while there is also growing awareness that not all models produce equally plausible or independent simulations. Therefore, many recent studies have investigated how models differ from observed climate and how model dependence affects model output similarity, typically drawing on climatological averages over several decades. Here, we show that temperature maps of individual days drawn from datasets never used in training can be robustly identified as “model” or “observation” using the CMIP6 model archive and four observational products. An important exception is a prototype storm-resolving simulation from ICON-Sapphire which cannot be unambiguously assigned to either category. These results highlight that persistent differences between simulated and observed climate emerge at short timescales already, but very high-resolution modeling efforts may be able to overcome some of these shortcomings. Moreover, temporally out-of-sample test days can be assigned their dataset name with up to 83% accuracy. Misclassifications occur mostly between models developed at the same institution, suggesting that effects of shared code, previously documented only for climatological timescales, already emerge at the level of individual days. Our results thus demonstrate that the use of machine learning classifiers, once trained, can overcome the need for several decades of data to evaluate a given model. This opens up new avenues to test model performance and independence on much shorter timescales.
Efficacy of a continuously active disinfectant wipe on the environmental bioburden in the intensive care unit: A randomized controlled study
Authors: Nadimpalli Gita , Johnson J. Kristie , Magder Laurence S. , Haririan Abdolreza , Stevens Deborah , Harris Anthony D. , O’Hara Lyndsay M.
Published: July 2023

Objective:

To evaluate the efficacy of a new continuously active disinfectant (CAD) to decrease bioburden on high-touch environmental surfaces compared to a standard disinfectant in the intensive care unit.

Design:

A single-blind randomized controlled trial with 1:1 allocation.

Setting:

Medical intensive care unit (MICU) at an urban tertiary-care hospital.

Participants:

Adult patients admitted to the MICU and on contact precautions.

Intervention:

A new CAD wipe used for daily cleaning.

Methods:

Samples were collected from 5 high-touch environmental surfaces before cleaning and at 1, 4, and 24 hours after cleaning. The primary outcome was the mean bioburden 24 hours after cleaning. The secondary outcome was the detection of any epidemiologically important pathogen (EIP) 24 hours after cleaning.

Results:

In total, 843 environmental samples were collected from 43 unique patient rooms. At 24 hours, the mean bioburden recovered from the patient rooms cleaned with the new CAD wipe (intervention) was 52 CFU/mL, and the mean bioburden was 92 CFU/mL in the rooms cleaned the standard disinfectant (control). After log transformation for multivariable analysis, the mean difference in bioburden between the intervention and control arm was −0.59 (95% CI, −1.45 to 0.27). The odds of EIP detection were 14% lower in the rooms cleaned with the CAD wipe (OR, 0.86; 95% CI, 0.31–2.32).

Conclusions:

The bacterial bioburden and odds of detection of EIPs were not statistically different in rooms cleaned with the CAD compared to the standard disinfectant after 24 hours. Although CAD technology appears promising in vitro, larger studies may be warranted to evaluate efficacy in clinical settings.
The importance of ‘acting yourself into new ways of thinking’: preliminary findings on the impact of embedding workplace experiences in law degrees to positively impact student skills growth, degree results and employment outcomes before and during a global pandemic
Authors: Perry Christina , Spencer Nigel
Published: July 2023

The paper reports the findings of over a decade of pioneering, award-winning fieldwork which has explored how workplace experience, if embedded successfully in different stages of legal education, can accelerate the ‘speed to capability’ and skills development of early career lawyers. The benefits from initial experiments of graduate-level work placements carried out by the authors since 2008 are presented. The paper then explores the findings from almost 10 years of creating year-long work placements for law undergraduates, assessing student skill growth, and the impact of the work placements on degree results and employment outcomes, before and during the Covid-19 pandemic.
Groups, conics and recurrence relations
Authors: Beardon A. F.
Published: July 2023

In this paper we explore some of the geometry that lies behind the real linear, second order, constant coefficient, recurrence relation
(1)
where a and b are real numbers. Readers will be familiar with the standard method of solving this relation, and, to avoid trivial cases, we shall assume that ab ≠ 0. The auxiliary equation of t2 = at + b of (1) has two (possibly complex) solutions

and the most general solution of (1) is given by

(i)

when are real and distinct;

(ii)

when

(iii)

.
Integer triangles with integer circumradii
Authors: Read Emrys
Published: July 2023

When studying properties of the circumcircle of an integer triangle, it quickly becomes evident that the radius of such a circle (circumradius) need not itself be an integer. When it is not an integer, the circumradius can still be rational but it can also be irrational, as exemplified in the following examples. It is left to the reader to verify that the triangle with sides 10, 24, 26 has circumradius 13, and that the corresponding values for the triangles with sides 13, 14, 15 and 1, 1, 1 are 65/8 and respectively. It is shown in Theorem 1 below that a necessary condition for the circumradius to be an integer is that the area of the triangle is itself an integer (Heronian triangle) but this condition is not in itself sufficient. A simple counterexample is given by the 13, 14, 15 triangle above which has area 84. However, as a consequence of Theorem 1, we can restrict ourselves to considering Heronian triangles, and relevant properties of such triangles, proved in [1], are given in Theorems 2 and 3 below. We also need to quote some well-known results involving the sums of two squares (see e.g. [2]) and these are listed in Lemma 3. In all that follows, we will use the convention that if T is a triangle with sides a, b, c and z > 0, then zT will denote the triangle, similar to T, with sides za, zb, zc.
Regression of binary network data with exchangeable latent errors
Authors: Marrs Frank W. , Fosdick Bailey K.
Published: July 2023

Undirected, binary network data consist of indicators of symmetric relations between pairs of actors. Regression models of such data allow for the estimation of effects of exogenous covariates on the network and for prediction of unobserved data. Ideally, estimators of the regression parameters should account for the inherent dependencies among relations in the network that involve the same actor. To account for such dependencies, researchers have developed a host of latent variable network models; however, estimation of many latent variable network models is computationally onerous and which model is best to base inference upon may not be clear. We propose the probit exchangeable (PX) model for undirected binary network data that is based on an assumption of exchangeability, which is common to many of the latent variable network models in the literature. The PX model can represent the first two moments of any exchangeable network model. We leverage the EM algorithm to obtain an approximate maximum likelihood estimator of the PX model that is extremely computationally efficient. Using simulation studies, we demonstrate the improvement in estimation of regression coefficients of the proposed model over existing latent variable network models. In an analysis of purchases of politically aligned books, we demonstrate political polarization in purchase behavior and show that the proposed estimator significantly reduces runtime relative to estimators of latent variable network models, while maintaining predictive performance.
A Holocene pollen-inferred climate reconstruction for Vermont, USA
Authors: Grigg Laurie D. , Stefanescu Ioana C. , Shuman Bryan N. , Oswald W. Wyatt
Published: July 2023

A 13.0 cal ka BP pollen record from Twin Ponds, Vermont, provides new insights into the climate history of the northeastern United States. Modern analogs were used to produce qualitative and quantitative climate reconstructions for Twin Ponds. The Twin Ponds record was compared with nearby Knob Hill Pond to develop a Vermont reconstruction that was compared with reconstructions from two sites at a similar latitude. Postglacial warming at 11.5 cal ka BP followed a cool, wet Younger Dryas and was the largest temperature change of the record. The warmest, driest conditions occurred at ca. 9.0 cal ka BP, followed by an increase in moisture. Latitudinal and elevational shifts in the location of modern analogs from 5.7 to 4.0 cal ka BP were used to infer cooling and increased moisture during theTsuga canadensisdecline. Analysis of the timing of pollen events between the two Vermont sites suggests a more rapid decline inT. canadensisat the more northern Knob Hill Pond and further supports the possibility that colder temperatures contributed to this event. The other northern sites show similar trends until 2.5 cal ka BP, when precipitation in the easternmost site diverges, indicating the establishment of modern climatic gradients.
UNTARNISHED BOOKS AND VANISHED KINGS: NUMA, OVID AND ENNIUS
Authors: Pontiggia Ludovico
Published: July 2023

This article argues that the discovery of Pythagorean volumes in Numa's tomb in 181 b.c. may have played a significant role in the conception of the meeting between Numa and Pythagoras in the last book of Ovid's Metamorphoses, since several features of this event integrate very well into the discourse at the heart of Book 15 on the Greek origins of Roman culture and literature, on the immortality of poetry, and on the relationship between poetry and power. The article further argues that Ennius’ Annals Book 15 may have covered the events up to 179, if that really was the year of Nobilior's dedication of the Aedes Herculis Musarum, and included the discovery of Numa's books in 181; and hence that Ovid may have used the Ennian account of this discovery as a model for the Numa–Pythagoras episode, appropriating the poetic and political meaning that it already had in Annals Book 15.
Striking a Balance between Protecting the Matrimonial Home and the Mortgagee's Right of Sale in Nigeria: Lessons from England
Authors: Ehiemua Roseline Omoye
Published: July 2023

This article evaluates statutory provisions and case law regarding a mortgagee's rights to exercise its statutory power of sale over the matrimonial home in Nigeria. It reveals that no statute protects the rights of family members, particularly wives and children, in the mortgaged home. The mortgagee must grapple with the reality of ownership, as wives often resort to litigation to set aside sales, on the ground that they are joint owners with their husbands. Ironically, some Supreme Court decisions, while protecting the interests of other family members (contrary to the established principles of property law), have tended to ignore the mortgagee's power of sale over the mortgaged matrimonial home, thus making it unattractive to lending institutions as collateral. This article recommends that all parties’ interests should be set out in a legal framework, as in England, where a non-owning spouse's right of occupation must be registered with the land registry.
Description of Anaplectus deconincki n. sp. from South Africa
Authors: Shokoohi E. , Eisenback J.
Published: July 2023

During a survey of soil nematodes in Kirstenbosch National Botanical Garden in Cape Town, a population of plectid nematodes belonging to the genus Anaplectus was recovered and proved to be a species new to science. Anaplectus deconincki n. sp. is characterized by female body length (612–932 μm), b = 4.6–5.2, c = 12.8–18.0, c’ = 2.6–3.1, V = 51–54, and tail length (43–63 μm). Males are characterized by body length (779–956 μm), b = 4.8–5.6, c = 13.9–16.7, c’ = 2.2–2.5, spicule length 33–39 μm, gubernaculum length 10–12 μm, and tail length (56–65 μm). Discriminant analysis clearly separated A. deconincki n. sp. from the other related species of Aanaplectus. The phylogenetic analysis placed Anaplectus deconincki n. sp. in a clade with 1.00 posterior probability values with other Anaplectus. Partial sequences of the 18S and 28S regions of the ribosomal DNA gene were amplified for Anaplectus deconincki n. sp., and 18S rDNA showed 99% similarity with an unidentified Anaplectus (AJ966473) and A. porosus (MF622934) from Belgium. In addition, 28S rDNA showed a 93% similarity with A. porosus from Belgium (MF622938) and a 98% similarity with A. granulosus from Germany (MF325171). Measurements, illustrations, and light microscopy pictures for Anaplectus deconincki n. sp. are given.
Beyond Cyril? Martin Luther's quest for christological agency
Authors: Małysz Piotr J.
Published: July 2023

This article examines a long-standing association of Martin Luther's christology with that of Cyril of Alexandria. However, for all its heuristic promise, the designation ‘Cyrillian’, must in Luther's case be understood either as an overly generalised statement of a well-established grammar of christology – in which case it simply is Luther's foundation and, as such, explains nothing specific about Luther's christology and, moreover, fails to do justice to the reformer's crucial argumentative moves. Alternatively, when taken for a set of material similarities, the designation is simply inaccurate, for Luther is decidedly not a Cyrillian, despite some fundamental convergences with the thought of the Alexandrian patriarch. Luther's context, as we demonstrate, leads him not only to go beyond Cyril, but also to argue in a manner contrary to Cyril, in order to secure what for both theologians is a realist eucharistic backdrop of their commitment to the Word's incarnation.
Language anxiety and learner silence in the classroom from a cognitive-behavioral perspective
Authors: Maher Kate , King Jim
Published: July 2023

Language anxiety plays a key role in language learners’ silent behaviors in class (King, 2013). Given its public nature and emphasis on interaction within it, the classroom context plays a significant role in the production of language anxiety. Anxious people are more likely to negatively appraise situations, affecting their behavior. That is, it is not just the subject content that causes anxiety, it is also the cognitive processes that occur from being in the classroom environment (Clark & Wells, 1995; Horwitz et al., 2010). King (2014) found that anxious language learners’ thoughts often containfeared predictionsabout the social costs of speaking in the classroom and worries about how peers might negatively evaluate performance. These fears about external factors contribute to learners becoming inhibited and using silence to avoid the discomfort of speaking. Also, while anxious learners tend to have content-specific concerns, for example, making mistakes, self-focused thoughts are often intensified by contextual factors, such as interacting with peers (Gregersen & Horwitz, 2002). This article looks at the relationship between language anxiety and silent behavior from a cognitive-behavioral perspective, emphasizing how the dynamic interplay between an individual learner and the classroom context can result in even the most motivated and proficient learners missing opportunities to develop their language skills through target-language interaction.
A primer on measurement invariance in L2 anxiety research
Authors: Sudina Ekaterina
Published: July 2023

Measurement invariance (MI) is essential to bolstering validity arguments behind psychometric instruments (Zumbo, 2007). Nonetheless, very few second language (L2) anxiety scales, including the most widely used L2 anxiety questionnaire—the Foreign Language Classroom Anxiety Scale (FLCAS; Horwitz et al., 1986)—have been tested for MI. The present paper seeks to address this deficiency in the literature (a) by demonstrating why this procedure is key to enhancing our understanding of the latent phenomenon in question, particularly in relation to different language learning contexts, (b) by outlining the main stages of MI testing with specific recommendations for L2 scale developers and users, (c) by providing commendable examples of the application of MI in applied linguistics research in order to illustrate the potential of this technique, and (d) by making a case for employing MI in future validation studies, thereby promoting methodologically sound research practices in the context of anxiety scales and elsewhere in applied linguistics.
The so-called “one-and-a-half” ventricular repair: where are we after 40 years?
Authors: Chowdhury Ujjwal Kumar , Anderson Robert H. , Pandey Niraj Nirmal , Mishra Sundeep , Sankhyan Lakshmi Kumari , George Niwin , Khan Maroof A. , Goja Shikha
Published: July 2023

Objectives:

The indications, timing, and results of the so-called “one-and-a-half ventricle repair”, as a surgical alternative to the creation of the Fontan circulation, or high-risk biventricular repair, currently remain nebulous. We aimed to clarify these issues.

Methods:

We reviewed a total of 201 investigations, assessing selection of candidates, the need for atrial septal fenestration, the fate of an unligated azygos vein and free pulmonary regurgitation, the concerns regarding reverse pulsatile flow in the superior caval vein, the growth potential and function of the subpulmonary ventricle, and the role of the superior cavopulmonary connections as an interstage procedure prior to biventricular repair, or as a salvage procedure. We also assessed subsequent eligibility for conversion to biventricular repair and long-term functional results.

Results:

Reported operative mortalities ranged from 3% to 20%, depending on the era of surgical repair with 7% risk of complications due to a pulsatile superior caval vein, up to one-third incidence of supraventricular arrhythmias, and a small risk of anastomotic takedown of the superior cavopulmonary connection. Actuarial survival was between 80% and 90% at 10 years, with two-thirds of patients in good shape after 20 years. We found no reported instances of plastic bronchitis, protein-losing enteropathy, or hepatic cirrhosis.

Conclusions:

The so-called “one-and-a-half ventricular repair”, which is better described as production of one-and-a-half circulations can be performed as a definitive palliative procedure with an acceptable risk similar to that of conversion to the Fontan circulation. The operation reduces the surgical risk for biventricular repair and reverses the Fontan paradox.
Adherence to the Swedish dietary guidelines and the impact on mortality and climate in a population-based cohort study
Authors: Strid Anna , Hallström Elinor , Lindroos Anna Karin , Lindahl Bernt , Johansson Ingegerd , Winkvist Anna
Published: July 2023

Objective:

To assess the associations between adherence to the Swedish dietary guidelines and all-cause mortality (i.e. assessing the index’ ability to predict health outcomes), as well as levels of dietary greenhouse gas emissions (GHGEs).

Design:

A longitudinal study 1990–2016 within the population-based cohort Västerbotten Intervention Programme. Dietary data were based on FFQs. Diet quality was assessed by the Swedish Healthy Eating Index for Adults 2015 (SHEIA15), based on the 2015 Swedish dietary guidelines. Dietary GHGEs were estimated from life cycle assessment data including emissions from farm to industry gate. Hazard ratios (HR) and 95 % CI of all-cause mortality were evaluated with Cox proportional hazards regression, and differences in median GHGEs were tested between quintiles of SHEIA15 score using the Kruskal–Wallis one-way ANOVA test.

Setting:

Northern Sweden.

Participants:

In total, 49 124 women and 47 651 men, aged 35–65 years.

Results:

Median follow-up times were 16·0 years for women and 14·7 years for men, during which time 3074 women and 4212 men died. A consistent trend of lower all-cause mortality HR for both sexes with higher SHEIA15 scores was demonstrated. For women, the all-cause mortality HR was 0·81 ((95 % CI 0·71, 0·92); P = 0·001) and for men 0·90 ((95 % CI 0·81, 0·996); P = 0·041) between the quintile with the highest SHEIA15 score compared with the quintile with the lowest SHEIA15 score. A consistent trend of lower estimated dietary GHGEs among both sexes with higher SHEIA15 scores was also found.

Conclusions:

Adherence to Swedish dietary guidelines, estimated by SHEIA15, seems to promote longevity and reduce dietary climate impact.
The Association between ideology and resistance to governmental apology depends on political knowledge
Authors: Inamasu Kazunori , Kohama Shoko , Mifune Nobuhiro , Ohtsubo Yohsuke , Tago Atsushi
Published: July 2023

This study examines the relationship between ideology and resistance to the government's apology to Asian victims of Japan's colonial rule policy, which varies according to political knowledge. Based on existing research, because only a limited percentage of voters consider politics to be ideology based, it is expected that the association between ideology and resistance to intergroup apologies by one's own government differs according to their level of political knowledge. We selected three issues of political apologies: colonial rule in Asian countries, comfort women, and the massacre of Korean people based on false rumors at the time of the 1923 Kanto Earthquake; thereafter, we conducted an online survey of a panel selected by Nikkei Research Inc. The results suggest that the relationship between ideology and resistance among voters to political apologies varies with the level of political knowledge, as expected. On the contrary, social dominance orientations (SDO) were associated with resistance to apology, regardless of their level of political knowledge. We then tested the reproducibility of this finding by conducting a follow-up test on registered users of a crowdsourcing service after conducting a preregistration. In addition, we also measured general attitudes toward personal apologies and neighboring countries victimized by Japan's colonialist policies as factors that might predict resistance to apologies even among the politically uninformed. The association between ideology, SDO, and resistance to governmental apologies was generally replicated in this study.
Overexpression of geraniol-10-hydroxylase improves valtrate accumulation in Valeriana jatamansi
Authors: Zhao Shuang
Published: July 2023

Valtrate is the major active component of iridoids in Valeriana jatamansi plants, and has been widely used for the treatment of various diseases, giving rise to rapidly increasing market demands. The gene VjG10H from V. jatamansi encoding geraniol 10-hydroxylase (G10H) was introduced into V. jatamansi hairy roots and a transgenic hairy root culture system of V. jatamansi with good valtrate production ability was successfully established for the first time. The valtrate content of VjG10H-transformed lines ranged from 8.12 to 10.77 mg/g, with an average valtrate content (9.52 mg/g) of all the four G lines being higher than the non-transgenic hairy root line. Overexpression of VjG10H significantly improved valtrate production, indicating that G10H played an important role in stimulating valtrate accumulation. MeJA treatment stimulated valtrate accumulation in all of the VjG10H overexpression recombinant lines compared to untreated cultures, indicating that methyl jasmonate treatment was another effective regulation target for metabolic engineering of valtrate biosynthesis in V. jatamansi. Thus, transgenic hairy root technology coupled with elicitor treatments may be a promising strategy to increase valtrate yield in V. jatamansi.
Entwicklung und Validierung einer deutschsprachigen Skala zur Erfassung von Kontakterfahrungen gegenüber gesundheitlich eingeschränkten Menschen (CDP-D)
Authors: Slavchova Veneta , Heßhaus Verena , Knispel Jens , Arling Viktoria
Published: July 2023

Zusammenfassung: Kontakterfahrungen mit gesundheitlich beeinträchtigten Menschen können von gesunden Menschen unterschiedlich empfunden werden (positiv, neutral, negativ). Um entsprechende Begegnungen vor dem Hintergrund der Inklusionsthematik beschreibbar zu machen, ist ein validiertes Messinstrument erforderlich. Ziel der Studie ist es, eine deutschsprachige Skala zur Erfassung von Kontakterfahrungen mit gesundheitlich eingeschränkten Personen zu entwickeln und zu validieren. Als Ausgangslage diente die englischsprachige Revision der Contact with disabled persons – Skala (CDP-Skala) von Pruett et al. (2008 ). Die Prüfversion der deutschsprachigen Skala (CDP-D) wurde in einer Online-Stichprobe ( N = 1 092) erprobt. Nach einer Reduktion von 20 auf 13 Items ergab sich eine zufriedenstellende Modellpassung für positive, neutrale und negative Kontakterfahrungen (dimensionale Validität). Die CDP-D-Skala erfüllt die Anforderungen strikter Messinvarianz (Bezugsrahmen, Geschlecht, Alter). Es berechnen sich differenzierte Korrelationen der CDP-D-Subskalen mit Motivation zu vorteilsfreiem Verhalten, Autoritarismus und sozialer Dominanzorientierung (Konstruktvalidität). Die CDP-D-Subskalen haben einen inkrementellen Mehrwert in hierarchischen binär-logistischen Regressionsanalysen mit fiktiven Personalauswahlszenarien zur Messung von Inklusionsbereitschaft (Kriteriumsvalidität).
Quantifying Net Community Production and Calcification at Station ALOHA Near Hawai'i: Insights and Limitations From a Dual Tracer Carbon Budget Approach
Authors: Knor Lucie A. C. M. , Sabine Christopher L. , Sutton Adrienne J. , White Angelicque E. , Potemra James , Weller Robert A.
Published: July 2023

A budget approach is used to disentangle drivers of the seasonal mixed layer carbon cycle at Station ALOHA (A Long‐term Oligotrophic Habitat Assessment) in the North Pacific Subtropical Gyre (NPSG). The budget utilizes data from the WHOTS (Woods Hole—Hawaii Ocean Time‐series Site) mooring, and the ship‐based Hawai'i Ocean Time‐series (HOT) in the NPSG, a region of significant oceanic carbon uptake. Parsing the carbon variations into process components allows an assessment of both the proportional contributions of mixed layer carbon drivers and the seasonal interplay of drawdown and supply from different processes. Annual net community production reported here is at the lower end of previously published data, while net community calcification estimates are 4‐ to 7‐fold higher than available sediment trap data, the only other estimate of calcium carbonate export at this location. Although the observed seasonal cycle in dissolved inorganic carbon in the NPSG has a relatively small amplitude, larger fluxes offset each other over an average year. Major supply comes from physical transport, especially lateral eddy transport throughout the year and entrainment in the winter, offset by biological carbon uptake in the spring. Gas exchange plays a smaller role, supplying carbon to the surface ocean between Dec‐May and outgassing in Jul‐Oct. Evaporation‐precipitation (E‐P) is variable with precipitation prevailing in the first half and evaporation in the second half of the year. The observed total alkalinity signal is largely governed by E‐P with a somewhat stronger net calcification signal in the wintertime.
How Well do Earth System Models Capture Apparent Relationships Between Phytoplankton Biomass and Environmental Variables?
Authors: Holder Christopher , Gnanadesikan Anand
Published: July 2023

As phytoplankton form the base of the marine food web, understanding the controls on their abundance is fundamental to understanding marine ecology and its sensitivity to global climate change. While many Earth System Models (ESMs) predict phytoplankton biomass, it is unclear whether they properly capture the mechanistic relationships that control this quantity in the real ocean. We used Random Forest analysis to analyze the output of 13 ESMs as well as two observational data sets. The target variable was phytoplankton carbon and the predictors included environmental parameters known to influence phytoplankton, including nutrients, light, mixed layer depth, salinity, temperature, and upwelling. We examined the following: (a) What fractions of variability in ESMs and observations can be linked to the large‐scale environmental variables simulated by ESMs? (b) What are the dominant predictors and relationships affecting phytoplankton biomass? (c) How well do ESMs simulate phytoplankton carbon and do they simulate the relationships we see in observations? About 88%–96% of the variability in observational data sets and greater than 98% in the ESMs was accounted for by environmental variables known to influence phytoplankton biomass. The dominant predictors in the observational data sets were shortwave radiation and dissolved iron, with temperature and ammonium also relatively important. All the ESMs show that shortwave radiation is the most important variable and most of them predict the right sign of sensitivity to most variables. However, the models predict that biomass reaches maximum levels at unrealistically low levels of iron and unrealistically high levels of light.
Histone modifications in drug-resistant cancers: From a cancer stem cell and immune evasion perspective
Authors: Jin Ming Li , Jeong Kwang Won
Published: July 2023

The development and immune evasion of cancer stem cells (CSCs) limit the efficacy of currently available anticancer therapies. Recent studies have shown that epigenetic reprogramming regulates the expression of characteristic marker proteins and tumor plasticity associated with cancer cell survival and metastasis in CSCs. CSCs also possess unique mechanisms to evade external attacks by immune cells. Hence, the development of new strategies to restore dysregulated histone modifications to overcome cancer resistance to chemotherapy and immunotherapy has recently attracted attention. Restoring abnormal histone modifications can be an effective anticancer strategy to increase the therapeutic effect of conventional chemotherapeutic and immunotherapeutic drugs by weakening CSCs or by rendering them in a naïve state with increased sensitivity to immune responses. In this review, we summarize recent findings regarding the role of histone modifiers in the development of drug-resistant cancer cells from the perspectives of CSCs and immune evasion. In addition, we discuss attempts to combine currently available histone modification inhibitors with conventional chemotherapy or immunotherapy.
CD38/ADP-ribose/TRPM2-mediated nuclear Ca2+ signaling is essential for hepatic gluconeogenesis in fasting and diabetes
Authors: Rah So-Young , Joe Yeonsoo , Park Jeongmin , Ryter Stefan W. , Park Chansu , Chung Hun Taeg , Kim Uh-Hyun
Published: July 2023

Hepatic glucose production by glucagon is crucial for glucose homeostasis during fasting, yet the underlying mechanisms remain incompletely delineated. Although CD38 has been detected in the nucleus, its function in this compartment is unknown. Here, we demonstrate that nuclear CD38 (nCD38) controls glucagon-induced gluconeogenesis in primary hepatocytes and liver in a manner distinct from CD38 occurring in the cytoplasm and lysosomal compartments. We found that the localization of CD38 in the nucleus is required for glucose production by glucagon and that nCD38 activation requires NAD+ supplied by PKCδ-phosphorylated connexin 43. In fasting and diabetes, nCD38 promotes sustained Ca2+ signals via transient receptor potential melastatin 2 (TRPM2) activation by ADP-ribose, which enhances the transcription of glucose-6 phosphatase and phosphoenolpyruvate carboxykinase 1. These findings shed light on the role of nCD38 in glucagon-induced gluconeogenesis and provide insight into nuclear Ca2+ signals that mediate the transcription of key genes in gluconeogenesis under physiological conditions.
Ultra-compact fiber tapering: plasmonics and structural bending as new combination of heat and pull
Authors: Yang Tian
Published: July 2023

Fabrication of optical fiber tapers is realized with a combination of plasmonic microheaters and specially designed structural bending of optical fibers, which provide the necessary elements of “heat and pull”. The resultant compactness and flame-free condition enable monitoring of the tapering process inside a scanning electron microscope.
SIRT6 is an epigenetic repressor of thoracic aortic aneurysms via inhibiting inflammation and senescence
Authors: Ding Yang-Nan , Wang Ting-Ting , Lv Shuang-Jie , Tang Xiaoqiang , Wei Zi-Yu , Yao Fang , Xu Han-Shi , Chen Yi-Nan , Wang Xiao-Man , Wang Hui-Yu , Wang He-Ping , Zhang Zhu-Qin , Zhao Xiang , Hao De-Long , Sun Li-Hong , Zhou Zhou , Wang Li , Chen Hou-Zao , Liu De-Pei
Published: July 2023

Thoracic aortic aneurysms (TAAs) develop asymptomatically and are characterized by dilatation of the aorta. This is considered a life-threating vascular disease due to the risk of aortic rupture and without effective treatments. The current understanding of the pathogenesis of TAA is still limited, especially for sporadic TAAs without known genetic mutation. Sirtuin 6 (SIRT6) expression was significantly decreased in the tunica media of sporadic human TAA tissues. Genetic knockout of Sirt6 in mouse vascular smooth muscle cells accelerated TAA formation and rupture, reduced survival, and increased vascular inflammation and senescence after angiotensin II infusion. Transcriptome analysis identified interleukin (IL)-1β as a pivotal target of SIRT6, and increased IL-1β levels correlated with vascular inflammation and senescence in human and mouse TAA samples. Chromatin immunoprecipitation revealed that SIRT6 bound to the Il1b promoter to repress expression partly by reducing the H3K9 and H3K56 acetylation. Genetic knockout of Il1b or pharmacological inhibition of IL-1β signaling with the receptor antagonist anakinra rescued Sirt6 deficiency mediated aggravation of vascular inflammation, senescence, TAA formation and survival in mice. The findings reveal that SIRT6 protects against TAA by epigenetically inhibiting vascular inflammation and senescence, providing insight into potential epigenetic strategies for TAA treatment.
Human 3D brain organoids: steering the demolecularization of brain and neurological diseases
Authors: Adlakha Yogita K.
Published: July 2023

Understanding of human brain development, dysfunction and neurological diseases has remained limited and challenging due to inability to recapitulate human brain-specific features in animal models. Though the anatomy and physiology of the human brain has been understood in a remarkable way using post-mortem, pathological samples of human and animal models, however, modeling of human brain development and neurological diseases remains a challenge owing to distinct complexity of human brain. In this perspective, three-dimensional (3D) brain organoids have shown a beam of light. Tremendous growth in stem cell technologies has permitted the differentiation of pluripotent stem cells under 3D culture conditions into brain organoids, which recapitulate the unique features of human brain in many ways and also offer the detailed investigation of brain development, dysfunction and neurological diseases. Their translational value has also emerged and will benefit the society once the protocols for the upscaling of brain organoids are in place. Here, we summarize new advancements in methods for generation of more complex brain organoids including vascularized and mixed lineage tissue from PSCs. How synthetic biomaterials and microfluidic technology is boosting brain organoid development, has also been highlighted. We discuss the applications of brain organoids in studying preterm birth associated brain dysfunction; viral infections mediated neuroinflammation, neurodevelopmental and neurodegenerative diseases. We also highlight the translational value of brain organoids and current challenges that the field is experiencing.
Modeling and therapeutic targeting of inflammation-induced hepatic insulin resistance using human iPSC-derived hepatocytes and macrophages
Authors: Groeger Marko , Matsuo Koji , Heidary Arash Emad , Pereira Ashley , Le Guillou Dounia , Pino Cindy , Telles-Silva Kayque A. , Maher Jacquelyn J. , Hsiao Edward C. , Willenbring Holger
Published: July 2023

Hepatic insulin resistance is recognized as a driver of type 2 diabetes and fatty liver disease but specific therapies are lacking. Here we explore the potential of human induced pluripotent stem cells (iPSCs) for modeling hepatic insulin resistance in vitro, with a focus on resolving the controversy about the impact of inflammation in the absence of steatosis. For this, we establish the complex insulin signaling cascade and the multiple inter-dependent functions constituting hepatic glucose metabolism in iPSC-derived hepatocytes (iPSC-Heps). Co-culture of these insulin-sensitive iPSC-Heps with isogenic iPSC-derived pro-inflammatory macrophages induces glucose output by preventing insulin from inhibiting gluconeogenesis and glycogenolysis and activating glycolysis. Screening identifies TNFα and IL1β as the mediators of insulin resistance in iPSC-Heps. Neutralizing these cytokines together restores insulin sensitivity in iPSC-Heps more effectively than individual inhibition, reflecting specific effects on insulin signaling and glucose metabolism mediated by NF-κB or JNK. These results show that inflammation is sufficient to induce hepatic insulin resistance and establish a human iPSC-based in vitro model to mechanistically dissect and therapeutically target this metabolic disease driver.
Recurrent photic zone euxinia limited ocean oxygenation and animal evolution during the Ediacaran
Authors: Zheng Wang , Zhou Anwen , Sahoo Swapan K. , Nolan Morrison R. , Ostrander Chadlin M. , Sun Ruoyu , Anbar Ariel D. , Xiao Shuhai , Chen Jiubin
Published: July 2023

The Ediacaran Period (~635–539 Ma) is marked by the emergence and diversification of complex metazoans linked to ocean redox changes, but the processes and mechanism of the redox evolution in the Ediacaran ocean are intensely debated. Here we use mercury isotope compositions from multiple black shale sections of the Doushantuo Formation in South China to reconstruct Ediacaran oceanic redox conditions. Mercury isotopes show compelling evidence for recurrent and spatially dynamic photic zone euxinia (PZE) on the continental margin of South China during time intervals coincident with previously identified ocean oxygenation events. We suggest that PZE was driven by increased availability of sulfate and nutrients from a transiently oxygenated ocean, but PZE may have also initiated negative feedbacks that inhibited oxygen production by promoting anoxygenic photosynthesis and limiting the habitable space for eukaryotes, hence abating the long-term rise of oxygen and restricting the Ediacaran expansion of macroscopic oxygen-demanding animals.
A medullary hub for controlling REM sleep and pontine waves
Authors: Schott Amanda L. , Baik Justin , Chung Shinjae , Weber Franz
Published: July 2023

Rapid-eye-movement (REM) sleep is a distinct behavioral state associated with vivid dreaming and memory processing. Phasic bursts of electrical activity, measurable as spike-like pontine (P)-waves, are a hallmark of REM sleep implicated in memory consolidation. However, the brainstem circuits regulating P-waves, and their interactions with circuits generating REM sleep, remain largely unknown. Here, we show that an excitatory population of dorsomedial medulla (dmM) neurons expressing corticotropin-releasing-hormone (CRH) regulates both REM sleep and P-waves in mice. Calcium imaging showed that dmM CRH neurons are selectively activated during REM sleep and recruited during P-waves, and opto- and chemogenetic experiments revealed that this population promotes REM sleep. Chemogenetic manipulation also induced prolonged changes in P-wave frequency, while brief optogenetic activation reliably triggered P-waves along with transiently accelerated theta oscillations in the electroencephalogram (EEG). Together, these findings anatomically and functionally delineate a common medullary hub for the regulation of both REM sleep and P-waves.
Cucurbit[8]uril-based water-dispersible assemblies with enhanced optoacoustic performance for multispectral optoacoustic imaging
Authors: Wu Yinglong , Sun Lihe , Chen Xiaokai , Liu Jiawei , Ouyang Juan , Zhang Xiaodong , Guo Yi , Chen Yun , Yuan Wei , Wang Dongdong , He Ting , Zeng Fang , Chen Hongzhong , Wu Shuizhu , Zhao Yanli
Published: July 2023

Organic small-molecule contrast agents have attracted considerable attention in the field of multispectral optoacoustic imaging, but their weak optoacoustic performance resulted from relatively low extinction coefficient and poor water solubility restrains their widespread applications. Herein, we address these limitations by constructing supramolecular assemblies based on cucurbit[8]uril (CB[8]). Two dixanthene-based chromophores (DXP and DXBTZ) are synthesized as the model guest compounds, and then included in CB[8] to prepare host-guest complexes. The obtained DXP-CB[8] and DXBTZ-CB[8] display red-shifted and increased absorption as well as decreased fluorescence, thereby leading to a substantial enhancement in optoacoustic performance. Biological application potential of DXBTZ-CB[8] is investigated after co-assembly with chondroitin sulfate A (CSA). Benefiting from the excellent optoacoustic property of DXBTZ-CB[8] and the CD44-targeting feature of CSA, the formulated DXBTZ-CB[8]/CSA can effectively detect and diagnose subcutaneous tumors, orthotopic bladder tumors, lymphatic metastasis of tumors and ischemia/reperfusion-induced acute kidney injury in mouse models with multispectral optoacoustic imaging.
The plant nuclear lamina disassembles to regulate genome folding in stress conditions
Authors: Wang Nan , Wang Zhidan , Tzourtzou Sofia , Wang Xu , Bi Xiuli , Leimeister Julia , Xu Linhao , Sakamoto Takuya , Matsunaga Sachihiro , Schaller Andreas , Jiang Hua , Liu Chang
Published: July 2023

The nuclear lamina is a complex network of nuclear lamins and lamin-associated nuclear membrane proteins, which scaffold the nucleus to maintain structural integrity. In Arabidopsis thaliana, nuclear matrix constituent proteins (NMCPs) are essential components of the nuclear lamina and are required to maintain the structural integrity of the nucleus and specific perinuclear chromatin anchoring. At the nuclear periphery, suppressed chromatin overlapping with repetitive sequences and inactive protein-coding genes are enriched. At a chromosomal level, plant chromatin organization in interphase nuclei is flexible and responds to various developmental cues and environmental stimuli. On the basis of these observations in Arabidopsis, and given the role of NMCP genes (CRWN1 and CRWN4) in organizing chromatin positioning at the nuclear periphery, one can expect considerable changes in chromatin–nuclear lamina interactions when the global chromatin organization patterns are being altered in plants. Here we report the highly flexible nature of the plant nuclear lamina, which disassembles substantially under various stress conditions. Focusing on heat stress, we reveal that chromatin domains, initially tethered to the nuclear envelope, remain largely associated with CRWN1 and become scattered in the inner nuclear space. By investigating the three-dimensional chromatin contact network, we further reveal that CRWN1 proteins play a structural role in shaping the changes in genome folding under heat stress. Also, CRWN1 acts as a negative transcriptional coregulator to modulate the shift of the plant transcriptome profile in response to heat stress.
A catalog of bacterial reference genomes from cultivated human oral bacteria
Authors: Li Wenxi , Liang Hewei , Lin Xiaoqian , Hu Tongyuan , Wu Zhinan , He Wenxin , Wang Mengmeng , Zhang Jiahao , Jie Zhuye , Jin Xin , Xu Xun , Wang Jian , Yang Huanming , Zhang Wenwei , Kristiansen Karsten , Xiao Liang , Zou Yuanqiang
Published: July 2023

The oral cavity harbors highly diverse communities of microorganisms. However, the number of isolated species and high-quality genomes is limited. Here we present a Cultivated Oral Bacteria Genome Reference (COGR), comprising 1089 high-quality genomes based on large-scale aerobic and anaerobic cultivation of human oral bacteria isolated from dental plaques, tongue, and saliva. COGR covers five phyla and contains 195 species-level clusters of which 95 include 315 genomes representing species with no taxonomic annotation. The oral microbiota differs markedly between individuals, with 111 clusters being person-specific. Genes encoding CAZymes are abundant in the genomes of COGR. Members of the Streptococcus genus make up the largest proportion of COGR and many of these harbor entire pathways for quorum sensing important for biofilm formation. Several clusters containing unknown bacteria are enriched in individuals with rheumatoid arthritis, emphasizing the importance of culture-based isolation for characterizing and exploiting oral bacteria.
Prospective controlled study on the effects of deep brain stimulation on driving in Parkinson’s disease
Authors: Fründt Odette , Mainka Tina , Vettorazzi Eik , Baspinar Ela , Schwarz Cindy , Südmeyer Martin , Gerloff Christian , Zangemeister Wolfgang H. , Poetter-Nerger Monika , Hidding Ute , Hamel Wolfgang , Moll Christian K. E. , Buhmann Carsten
Published: July 2023

To explore the influence of bilateral subthalamic deep brain stimulation (STN-DBS) on car driving ability in patients with Parkinson’s disease (PD), we prospectively examined two age-matched, actively driving PD patient groups: one group undergone DBS-surgery (PD-DBS, n = 23) and one group that was eligible for DBS but did not undergo surgery (PD-nDBS, n = 29). In PD-DBS patients, investigation at Baseline was done just prior and at Follow-up 6–12 month after DBS-surgery. In PD-nDBS patients, time interval between Baseline and Follow-up was aimed to be comparable. To assess the general PD driving level, driving was assessed once in 33 age-matched healthy controls at Baseline. As results, clinical and driving characteristics of PD-DBS, PD-nDBS and controls did not differ at Baseline. At Follow-up, PD-DBS patients drove unsafer than PD-nDBS patients. This effect was strongly driven by two single PD-DBS participants (9%) with poor Baseline and disastrous Follow-up driving performance. Retrospectively, we could not identify any of the assessed motor and non-motor clinical Baseline characteristics as predictive for this driving-deterioration at Follow-up. Excluding these two outliers, comparable driving performance between PD-DBS and PD-nDBS patients not only at Baseline but also at Follow-up was demonstrated. Age, disease duration and severity as well as Baseline driving insecurity were associated with poorer driving performance at Follow-up. This first prospective study on driving safety in PD after DBS surgery indicates that DBS usually does not alter driving safety but might increase the risk for driving deterioration, especially in single subjects with already unsafe driving prior to DBS surgery.