bluuebunny/crossref_metadata_2025 huggingface dataset:
Applying C:N ratio to assess the rationality of estimates of carbon sequestration in terrestrial ecosystems and nitrogen budgets
Authors: Cai Zucong , Yan Xiaoyuan , Gu Baojing
Published: June 2022

Carbon (C) sequestration in terrestrial ecosystems needs to ensure the reactive nitrogen (Nr) supply. However, the organic C:N ratio is rarely considered in both estimates of C sequestration in terrestrial ecosystems and N budget at regional and global scale. Here we propose an approach for extracting Nr sequestrated in terrestrial ecosystems with C (termed as Nrc) from N budget and then assessing the rationality of estimates of C sequestration in terrestrial ecosystems and N budgets by using the sequestrated organic C:N ratio as a criterion. We extracted Nrc from the N budget of IPCC AR5 at global scale and Chinese N budget (Proc Natl Acad Sci (USA) 112:8792, 2015) at regional scale based on the assumptions that there is no net Nr accumulation in agricultural products and no net Nr (except N2O) accumulation in the atmosphere at annual temporal scale, and N2O is not involved in biological processes. By taking the C sequestration in terrestrial ecosystems from C budget of IPCC AR5 (2.1 Pg C/yr during 2000–2009) to assess the N budget from the same report, the organic C:N ratios calculated by the Nrc extracted from both the upper ranges and averages of Nr input and output in global N budgets of IPCC AR5 fell outside the rational range of organic C:N ratio, but the organic C:N ratio (=31) calculated by the Nrc (68.1 Tg N/yr) extracted from the lower ranges of the N budget fell very well into the range of organic C:N ratio in global terrestrial ecosystems. Nrc extracted from Chinese N budget was 11.6 Tg N/yr in 2010, which could be combined with C into Chinese terrestrial ecosystems in a range between 0.14–0.66 Pg C/yr with a robust estimate of 0.36 Pg C/yr by applying the global terrestrial ecosystem sequestrated organic C:N ratio to calculation. The results indicate that the proposed approach for extracting Nrc from N budget works well. Checking the estimated organic C:N ratio in terrestrial ecosystems will help to assess whether the C and/or N budgets are rational or not.

Graphical abstract
Identification and classification of operating flow regimes and prediction of stall in a contra-rotating axial fan using machine learning
Authors: Kumar A. , Manas M.P. , Pradeep A.M.
Published: June 2022

Prediction of stall before it occurs, or detection of stall is crucial for smooth and lasting operation of fans and compressors. In order to predict the stall, it is necessary to distinguish the operational and stall regions based on certain parameters. Also, it is important to observe the variation of those parameters as the fan transitions towards stall. Experiments were performed on a contra-rotating fan setup under clean inflow conditions, and unsteady pressure data were recorded using seven high-response sensors circumferentially arranged on the casing, near the first rotor leading edge. Windowed Fourier analysis was performed on the pressure data, to identify different regions, as the fan transits from the operational to stall region. Four statistical parameters were identified to characterise the pressure data and reduce the number of data points. K-means clustering was used on these four parameters to algorithmically mark different regions of operation. Results obtained from both the analyses are in agreement with each other, and three distinct regions have been identified. Between the no-activity and stall regions, there is a transition region that spans for a short duration of time characterised by intermittent variation of abstract parameters and excitations of Fourier frequencies. The results were validated with five datasets obtained from similar experiments at different times. All five experiments showed similar trends. Neural Network models were trained on the clustered data to predict the operating region of the machine. These models can be used to develop control systems that can prevent the stalling of the machine.
QUEER (A)EDI-(M)OLOGY: ON CALLIMACHUS’AETIAPROLOGUE
Authors: Telò Mario
Published: June 2022

In the prologue of Callimachus’Aetia, every single word opens up a wide, virtually boundless spectrum of suggestions, intimations, and evocations. In this paper, I heed Callimachus’ formal intricacies, joining the decoding game that has vexed and entertained ancient and modern readers by homing in on the para-etymological potentialities of the verb ἀείδω (‘I sing’). I wish to explore the possibility that, in this architext of Callimachean programmatics, ‘singing’ may amount to a sort of aesthetic satisfaction in self-deprivation, with formal elements mobilizing a spiral of eating and non-eating. This exploration offers the opportunity to think about Callimachean ‘singing’ as a challenge to conventional notions of human subjectivity and to the very idea of poetic immortality, expressing something like the wish of apoète mauditnot for monumental permanence, but for a looping insistence. We may then see Callimachean aesthetics as less rarefied, aristocratic, and decorous than it is usually made out to be. In the recalcitrance, the unruly looping of poetic form, we may glimpse an aesthetic sense that is more subversive, shaped by temporal stuckness, a rejection of fulfillment, and a hunger that rejects the lack that is satisfaction. I first locate the possibility of an alternative para-etymologizing of ἀείδω within the prologue's discourse of corporeality, in its precarious opposition of thinness and fatness. I then search the epigram dedicated to Heraclitus and theHymn to Demeterfor traces of the restless aesthetics inherent in this para-etymologizing, which I will ultimately connect with queer temporality. The Callimachean hymn invites us to see the poetic persona of theAetia's proem in a new light—as a counterpart of the starving binge eater Erysichthon, Demeter's enemy, who is barely distinguishable from the goddess herself.
Origins of spousal cross-concordance for psychiatric disorders: a test of the social stress theory for alcohol use disorder
Authors: Salvatore Jessica E. , Larsson Lönn Sara , Sundquist Jan , Sundquist Kristina , Kendler Kenneth S.
Published: June 2022

Background

The authors sought to clarify the impact of spousal psychiatric disorders of differing severity [major depression or anxiety disorders (DAD) v. bipolar disorder or nonaffective psychosis (BPN)] on proband risk for alcohol use disorder (AUD) during marriage.

Methods

In a Swedish cohort (N = 744 628), associations between spousal DAD and BPN and proband AUD were estimated with Cox proportional hazards; associations between parental AUD, proband premarital AUD, and spousal lifetime DAD and BPN were estimated with logistic regression; and whether spousal DAD or BPN causally increased risk for AUD was evaluated with frailty models.

Results

Spousal premarital DAD, spousal marital-onset DAD, and spousal BPN (premarital or marital-onset) were associated with proband AUD during marriage [hazard ratios (HR) range 1.44–3.72]. Those with a parental or premarital history of AUD (v. without) were more likely to marry a spouse with DAD or BPN (odds ratios 1.22–2.77). Moving from an unaffected first spouse to a DAD-affected second spouse increased AUD risk in males (HR 2.90). Moving from an unaffected first spouse to a BPN-affected second spouse increased AUD risk (HRmales 3.96; HRfemales 5.64). Moving to an unaffected second spouse from a DAD-affected first spouse decreased AUD risk, with stronger evidence in females compared to males (HRmales 0.59; HRfemales 0.28).

Conclusions

Associations between spousal DAD or BPN and proband AUD reflect both selection and causal effects. Marriage to a BPN-affected spouse has a particularly strong effect on AUD risk, with more modest effects for spousal DAD.
Global Estimates of Biogenic Methane Production in Marine Sediments Using Machine Learning and Deterministic Modeling
Authors: Lee T. R. , Phrampus B. J. , Skarke A. , Wood W. T.
Published: June 2022

We have developed a model of geospatially estimating carbon accumulation and methanogenesis in seabed sediments that uses more accurate and sophisticated inputs to models than used in previous estimates. Using this hybrid stochastic and deterministic model, we estimate the maximum carbon available for methanogenesis in the global seabed, and subsequent microbial methane generated as a function of location and depth (including the gas hydrate stability zone). Global integration over present and previously microbially reactive sediments column yields total carbon and methane to be ∼0.8–2.2 × 106 and 1.1–3.0 × 106 Pg C and CH4, respectively. Our improvements to accuracy include using geospatially machine learned estimates of seafloor inputs to which the methanogenesis modeling is most sensitive (e.g., total organic carbon, heat flux, porosity). Our improvements to model sophistication include geospatially dependent modeling (on a 5 × 5 arc‐minute grid), a new model of sediment compaction (allowing for non‐linear geothermal gradients), and variable age versus depth at each grid cell. A carbon reservoir of the magnitude we estimate here is consistent with the recent IPCC suggestion that long‐term carbon sinks could explain imbalances in reduction of atmospheric CO2 over the last 50 million years. Our technique provides a foundation of using globally updateable machine learning parameters as the input to geologic and geochemical models, allowing for new observations to update global budgets of carbon available for methane, and subsequent total estimates of seabed methane.
Formation of Olivine Veins by Reactive Fluid Flow in a Dehydrating Serpentinite
Authors: Huber K. , Vrijmoed J. C. , John T.
Published: June 2022

Many exposed high‐pressure meta‐serpentinites comprise a channelized network of olivine‐rich veins that formed during dehydration at depth and allowed the fluid to escape from the dehydrating rock. While previous studies have shown that chemical heterogeneities in rocks can control the formation of olivine‐enriched vein‐like interconnected porosity networks on the sub‐millimeter scale, it is still unclear how these networks evolve toward larger scales and develop nearly pure olivine veins. To explore this, we study the effect of reactive fluid flow on a dehydrating serpentinite. We use thermodynamic equilibrium calculations to investigate the effect of variations in the bulk silica content in serpentinites on the dehydration reaction of antigorite + brucite = olivine + fluid and the silica content of this fluid phase. Further, we develop a numerical model that combines the effects of intrinsic chemical heterogeneities with reactive transport with dissolved silica as metasomatic agent. Our model shows how reactive transport can lead to vein widening and olivine enrichment within a vein in an antigorite‐rich matrix, such as observed in the veins of the Erro Tobbio meta‐serpentinites. This is a critical step in the evolution toward larger‐scale vein systems and in the evolution of dynamic porosity, as this step helps account for the chemical feedback between the dehydrating rock and the liberated fluid.
Ammonium Sensitivity of Biological Nitrogen Fixation by Anaerobic Diazotrophs in Cultures and Benthic Marine Sediments
Authors: Darnajoux Romain , Reji Linta , Zhang Xin Rei , Luxem Katja E. , Zhang Xinning
Published: June 2022

New bioavailable nitrogen (N) from biological nitrogen fixation (BNF) is critical for the N budget and productivity of marine ecosystems. Nitrogen‐fixing organisms typically inactivate BNF when less metabolically costly N sources, like ammonium (NH4+), are available. Yet, several studies have observed BNF in benthic marine sediments linked to anaerobic sulfate‐reducing bacteria and fermenting firmicutes despite high porewater NH4+ concentrations (10–1,500 μM). To better understand the regulating controls and importance of benthic marine BNF, we evaluate BNF sensitivity to NH4+ in benthic diazotrophs using incubations of increasing biogeochemical complexity. BNF by cultures of model anaerobic diazotrophs (sulfate‐reducer Desulfovibrio vulgaris var. Hildenborough, fermenter Clostridium pasteurianum strain W5), sulfate‐reducing sediment enrichment cultures, and sediments from three Northeastern salt marshes (USA) is highly sensitive to external NH4+. BNF is inhibited by NH4+ beyond an apparent threshold [NH4+] of 2 μM in liquid cultures, most closely reflecting the true cellular sensitivity of BNF to NH4+. Sediment slurries exhibited an apparent threshold [NH4+] of 9 μM. Consistent with other studies, we find SRB‐like nitrogenase (nifH) gene and transcripts are prevalent in sediments. Our survey of porewater NH4+ data from diverse sediments suggests the broad applicability of inhibition thresholds measured here and confinement of benthic BNF to surficial sediments. Variations in BNF inhibition timing, NH4+ uptake rate, sediment composition, and biophysics could affect measurements of the apparent sensitivity of benthic BNF to NH4+. We propose NH4+ transporter affinity as a fundamental mechanistic constraint on NH4+ control of cellular BNF to improve biogeochemical models of N cycling.
The Timing of Collision Between Asia and the West Burma Terrane, and the Development of the Indo‐Burman Ranges
Authors: Najman Yani , Sobel Edward R. , Millar Ian , Luan Xiwu , Zapata Sebastian , Garzanti Eduardo , Parra Mauricio , Vezzoli Giovanni , Zhang Peng , Wa Aung Day , Paw Saw Mu Tha Lay , Lwin Thae Naung
Published: June 2022

The West Burma Terrane (WBT) is a small terrane bounded to the east by the Asian Sibumasu Block and to the west by the Indo‐Burman Ranges (IBR), the latter being an exhumed accretionary prism that formed during subduction of Indian oceanic lithosphere beneath Asia. Understanding the geological history of the WBT is important for reconstruction of the closure history of the Tethys Ocean and India‐Asia collision. Currently there are major discrepancies in the proposed timings of collision between the WBT with both India and Asia; whether the WBT collided with India or Asia first is debated, and proposed timings of collisions stretch from the Mesozoic to the Cenozoic. We undertook a multi‐technique provenance study involving petrography, detrital zircon U‐Pb and Hf analyses, rutile U‐Pb analyses and Sr‐Nd bulk rock analyses on sediments of the Central Myanmar Basins of the WBT. We determined that the first arrival of Asian material into the basin occurred after the earliest late Eocene and by the early Oligocene, thus placing a minimum constraint on the timing of WBT‐Asia collision. Our low temperature thermochronological study of the IBR records two periods of exhumation, in the early‐middle Eocene, and at the Oligo‐Miocene boundary. The Eocene event may be associated with the collision of the WBT with India. The later event at the Oligo‐Miocene boundary may be associated with changes in wedge dynamics resulting from increased sediment supply to the system; however a number of other possible causes provide equally plausible explanations for both events.
Without Deep Emissions Cuts, Marine Species Face Mass Extinction
Authors: Pardikar Rishika
Published: June 2022

On the basis of how much oxygen marine species need and how much is available, researchers predict extinctions comparable to those at the end of the Permian under a business-as-usual emissions scenario.
Algorithm Detects Thousands of Missing Levees from U.S. Database
Authors: Fritts Rachel
Published: June 2022

An existing levee database accounts for just one fifth of the country’s actual total levee count, limiting the study of how these embankments affect riparian ecosystem health in the United States.
Can We Better Predict Coastal Change?
Authors: Nienhuis Jaap , Grasso Florent , Goldstein Evan , Kopp Robert , Splinter Kristen , Tiampo Kristy
Published: June 2022

A new special collection invites studies on a new era of models and knowledge that provide predictions or insights into predictability in coastal geomorphology.
A Spatiotemporal Analysis of the COVID‐19 Pandemic in North Africa
Authors: Khedhiri Sami
Published: June 2022

Spatial panel‐data models are estimated to identify the factors of the prevalence of the coronavirus outbreak in North Africa. Using daily data on the number of cases collected between March 2020 and December 2021, three types of general models are investigated, and they include spatial spillovers between the neighboring countries of the region. In one model the spatial dependence is accounted for by adding a spatial lag of the dependent variable (SAR model). In an alternative specification, spatially correlated error terms are considered in the model (SEM), and in the third model a spatial lag dependent variable and spatially correlated errors are both added (SAC). To deal with unobservable individual heterogeneity, random and fixed individual effects specification are investigated in each of these models. The results of the maximum likelihood and generalized method of moments' estimations show that the lift of travel restrictions had an important impact on the spike in the numbers of COVID‐19 cases in North Africa and that the effects of endogenous interactions between the countries are strongly significant. It is found that spatial spillovers and a change in the travel policy are the main factors that can explain the mechanism of spread the coronavirus pandemic in North Africa. However, more data on socio‐demographic and behavioral variables and on vaccination rates are needed to better understand what caused the recent surge in the number of infections in the region.
Aftershock Regions of Aleutian‐Alaska Megathrust Earthquakes, 1938–2021
Authors: Tape Carl , Lomax Anthony
Published: June 2022

With five earthquakes (1938, 1946, 1957, 1964, and 1965), the Aleutian‐Alaska subduction plate boundary ruptured a length of 3,548 km. We revisit these five earthquakes—first studied in detail by Sykes (1971, https://doi.org/10.1029/JB076i032p08021)—through probabilistic relocation of carefully selected mainshocks and aftershocks. Our final catalog of 324 events is established from a set of 12 mainshocks that includes all Mw ≥ 7.7 megathrust earthquakes. Using the relocated catalog, we create revised aftershock regions delimited both parallel and normal to the trench. These aftershock regions exhibit significant differences from previous studies, with the following basic findings: the 10 November 1938 Mw 8.3 earthquake extended further west, to the Shumagin Islands, and further east, into the Kodiak region, relative to the prevailing aftershock region established by McCann et al. (1979, https://doi.org/10.1007/978-3-0348-6430-5_2). The 01 April 1946 Mw 8.6 sequence was anomalously concentrated near the trench, which implies near‐trench coseismic slip that contributed to the exceptionally large tsunami. The 09 March 1957 Mw 8.6 aftershocks spanned a 1,230 km length with numerous aftershocks within the outer‐rise region of the incoming Pacific plate. The 28 March 1964 Mw 9.2 aftershocks extended east into the Pamplona thrust system (south of Icy Bay, Alaska), suggesting coseismic rupture into this region; this is consistent with coseismic static displacements, as well as current estimates of interseismic locking. The post‐1965 events we examine are all smaller than the earlier events, but since they occurred in an era of improved data collection (seismic, geodetic, and tsunami), they provide a better opportunity for assessing the link between the distribution of aftershocks and the occurrence of coseismic, postseismic, and interseismic slip.
Ionospheric Turbulence: A Challenge for GPS Loss of Lock Understanding
Authors: De Michelis P. , Consolini G. , Pignalberi A. , Lovati G. , Pezzopane M. , Tozzi R. , Giannattasio F. , Coco I. , Marcucci M. F.
Published: June 2022

Ionospheric irregularities may affect electromagnetic signals propagating through the ionosphere and consequently contribute to the malfunctioning of the Global Navigation Satellite Systems hindering their accuracy and reliability. In this study, we use data recorded on board two of the three satellites of the Swarm constellation (namely, Swarm A and Swarm B) from 15 July 2014 to 31 December 2021 to assess the possible dependence of the Global Positioning System (GPS) signals loss of lock on the presence of a specific kind of ionospheric irregularities. To accomplish this task we study the scaling features of the electron density fluctuations through the structure function analysis simultaneously to the occurrence of loss of lock events through measurements recorded by the Langmuir probes and the precise orbit determination antennas on board Swarm A and Swarm B satellites. We find that the plasma density irregularities in a turbulent state characterized by intermittent structures and extremely high values of the Rate Of change of electron Density Index can lead to GPS loss of lock events. This is always true at mid and high latitudes, especially inside the auroral oval. In the equatorial belt, this happens in at least 75% of identified GPS loss of lock events that basically coincide with the occurrence of plasma bubbles.
The 5th edition of the World Health Organization Classification of Haematolymphoid Tumours: Myeloid and Histiocytic/Dendritic Neoplasms
Authors: Khoury Joseph D. , Solary Eric , Abla Oussama , Akkari Yassmine , Alaggio Rita , Apperley Jane F. , Bejar Rafael , Berti Emilio , Busque Lambert , Chan John K. C. , Chen Weina , Chen Xueyan , Chng Wee-Joo , Choi John K. , Colmenero Isabel , Coupland Sarah E. , Cross Nicholas C. P. , De Jong Daphne , Elghetany M. Tarek , Takahashi Emiko , Emile Jean-Francois , Ferry Judith , Fogelstrand Linda , Fontenay Michaela , Germing Ulrich , Gujral Sumeet , Haferlach Torsten , Harrison Claire , Hodge Jennelle C. , Hu Shimin , Jansen Joop H. , Kanagal-Shamanna Rashmi , Kantarjian Hagop M. , Kratz Christian P. , Li Xiao-Qiu , Lim Megan S. , Loeb Keith , Loghavi Sanam , Marcogliese Andrea , Meshinchi Soheil , Michaels Phillip , Naresh Kikkeri N. , Natkunam Yasodha , Nejati Reza , Ott German , Padron Eric , Patel Keyur P. , Patkar Nikhil , Picarsic Jennifer , Platzbecker Uwe , Roberts Irene , Schuh Anna , Sewell William , Siebert Reiner , Tembhare Prashant , Tyner Jeffrey , Verstovsek Srdan , Wang Wei , Wood Brent , Xiao Wenbin , Yeung Cecilia , Hochhaus Andreas
Published: June 2022

The upcoming 5th edition of the World Health Organization (WHO) Classification of Haematolymphoid Tumours is part of an effort to hierarchically catalogue human cancers arising in various organ systems within a single relational database. This paper summarizes the new WHO classification scheme for myeloid and histiocytic/dendritic neoplasms and provides an overview of the principles and rationale underpinning changes from the prior edition. The definition and diagnosis of disease types continues to be based on multiple clinicopathologic parameters, but with refinement of diagnostic criteria and emphasis on therapeutically and/or prognostically actionable biomarkers. While a genetic basis for defining diseases is sought where possible, the classification strives to keep practical worldwide applicability in perspective. The result is an enhanced, contemporary, evidence-based classification of myeloid and histiocytic/dendritic neoplasms, rooted in molecular biology and an organizational structure that permits future scalability as new discoveries continue to inexorably inform future editions.
The GABAA receptor modulator zolpidem augments hippocampal-prefrontal coupling during non-REM sleep
Authors: Kersanté Flavie , Purple Ross J. , Jones Matthew W.
Published: June 2022

Benzodiazepines and ‘Z-drugs’ (including zolpidem and zopiclone) are GABAA receptor (GABAAR) positive modulators commonly prescribed as hypnotics to treat insomnia and/or anxiety. However, alongside sedation, augmenting GABAAR function may also alter coordinated neuronal activity during sleep, thereby influencing sleep-dependent processes including memory consolidation. We used simultaneous recordings of neural population activity from the medial prelimbic cortex (PrL) and CA1 of the dorsal hippocampus (dCA1) of naturally sleeping rats to detail the effects of zolpidem on network activity during the cardinal oscillations of non-REM sleep. For comparison, we also characterized the effects of diazepam and 4,5,6,7-tetrahydroisoxazolo(5,4-c)pyridin-3-ol (THIP/gaboxadol), which acts predominantly at extra-synaptic GABAARs. Zolpidem and THIP significantly increased the amplitudes of slow-waves, which were attenuated by diazepam. Zolpidem increased hippocampal ripple density whereas diazepam decreased both ripple density and intrinsic frequency. While none of the drugs affected thalamocortical spindles in isolation, zolpidem augmented the temporal coordination between slow-waves and spindles. At the cellular level, analyses of spiking activity from 523 PrL and 579 dCA1 neurons revealed that zolpidem significantly enhanced synchronized pauses in cortical firing during slow-wave down states, while increasing correlated activity within and between dCA1 and PrL populations. Of the drugs compared here, zolpidem was unique in augmenting coordinated activity within and between hippocampus and neocortex during non-REM sleep. Zolpidem’s enhancement of hippocampal-prefrontal coupling may reflect the cellular basis of its potential to modulate offline memory processing.
The adrenal steroid profile in adolescent depression: a valuable bio-readout?
Authors: Hirtz Raphael , Libuda Lars , Hinney Anke , Föcker Manuel , Bühlmeier Judith , Holterhus Paul-Martin , Kulle Alexandra , Kiewert Cordula , Hauffa Berthold P. , Hebebrand Johannes , Grasemann Corinna
Published: June 2022

There is preliminary evidence that adrenal steroids other than cortisol may be valuable biomarkers for major depressive disorder (MDD). So far, studies have been conducted in adults only, and conclusions are limited, mainly due to small sample sizes. Therefore, the present study assessed whether adrenal steroids serve as biomarkers for adolescent MDD. In 261 depressed adolescents (170 females) treated at a single psychiatric hospital, serum adrenal steroids (progesterone, 17-hydroxyprogesterone, 21-deoxycortisol, 11-deoxycortisol, cortisol, cortisone, deoxycorticosterone, corticosterone) were determined by liquid chromatography-tandem mass spectrometry. Findings were compared to that of an age- and sex-matched reference cohort (N = 255) by nonparametric analysis of variance. Nonparametric receiver operating characteristics (ROC) analyses were conducted to evaluate the diagnostic performance of single steroids and steroid ratios to classify depression status. Sensitivity analyses considered important confounders of adrenal functioning, and ROC results were verified by cross-validation. Compared to the reference cohort, levels of deoxycorticosterone and 21-deoxycortisol were decreased (P < 0.001). All other glucocorticoid- and mineralocorticoid-related steroids were increased (P < 0.001). The corticosterone to deoxycorticosterone ratio evidenced excellent classification characteristics, especially in females (AUC: 0.957; sensitivity: 0.902; specificity: 0.891). The adrenal steroid metabolome qualifies as a bio-readout reflecting adolescent MDD by a distinct steroid pattern that indicates dysfunction of the hypothalamus–pituitary–adrenal axis. Moreover, the corticosterone to deoxycorticosterone ratio may prospectively qualify to contribute to precision medicine in psychiatry by identifying those patients who might benefit from antiglucocorticoid treatment or those at risk for recurrence when adrenal dysfunction has not resolved.
An mTOR and DNA-PK dual inhibitor CC-115 hinders non-small cell lung cancer cell growth
Authors: Chen Fagui , Zhao Huasi , Li Chenhui , Li Ping , Zhang Qichuan
Published: June 2022

Molecularly-targeted agents are still urgently needed for better non-small cell lung cancer (NSCLC) therapy. CC-115 is a potent DNA-dependent protein kinase (DNA-PK) and mammalian target of rapamycin (mTOR) dual blocker. We evaluated its activity in different human NSCLC cells. In various primary human NSCLC cells and A549 cells, CC-115 potently inhibited viability, cell proliferation, cell cycle progression, and hindered cell migration/invasion. Apoptosis was provoked in CC-115-stimulated NSCLC cells. The dual inhibitor, however, was unable to induce significant cytotoxic and pro-apoptotic activity in the lung epithelial cells. In primary NSCLC cells, CC-115 blocked activation of mTORC1/2 and DNA-PK. Yet, CC-115-induced primary NSCLC cell death was more potent than combined inhibition of DNA-PK plus mTOR. Further studies found that CC-115 provoked robust oxidative injury in primary NSCLC cells, which appeared independent of mTOR-DNA-PK dual blockage. In vivo studies showed that CC-115 oral administration in nude mice remarkably suppressed primary NSCLC cell xenograft growth. In CC-115-treated NSCLC xenograft tissues, mTOR-DNA-PK dual inhibition and oxidative injury were detected. Together, CC-115 potently inhibits NSCLC cell growth.
Chromosome-level and haplotype-resolved genome provides insight into the tetraploid hybrid origin of patchouli
Authors: Shen Yanting , Li Wanying , Zeng Ying , Li Zhipeng , Chen Yiqiong , Zhang Jixiang , Zhao Hong , Feng Lingfang , Ma Dongming , Mo Xiaolu , Ouyang Puyue , Huang Lili , Wang Zheng , Jiao Yuannian , Wang Hong-bin
Published: June 2022

Patchouli (Pogostemon cablin (Blanco) Benth.), a member of the Lamiaceae family, is an important aromatic plant that has been widely used in medicine and perfumery. Here, we report a 1.94 Gb chromosome-scale assembly of the patchouli genome (contig N50 = 7.97 Mb). The gene annotation reveals that tandem duplication of sesquiterpene biosynthetic genes may be a major contributor to the biosynthesis of patchouli bioactivity components. We further phase the genome into two distinct subgenomes (A and B), and identify a chromosome substitution event that have occurred between them. Further investigations show that a burst of universal LTR-RTs in the A subgenome lead to the divergence between two subgenomes. However, no significant subgenome dominance is detected. Finally, we track the evolutionary scenario of patchouli including whole genome tetraploidization, subgenome divergency, hybridization, and chromosome substitution, which are the key forces to determine the complexity of patchouli genome. Our work sheds light on the evolutionary history of patchouli and offers unprecedented genomic resources for fundamental patchouli research and elite germplasm development.
Marine siliceous ecosystem decline led to sustained anomalous Early Triassic warmth
Authors: Isson Terry T. , Zhang Shuang , Lau Kimberly V. , Rauzi Sofia , Tosca Nicholas J. , Penman Donald E. , Planavsky Noah J.
Published: June 2022

In the wake of rapid CO2release tied to the emplacement of the Siberian Traps, elevated temperatures were maintained for over five million years during the end-Permian biotic crisis. This protracted recovery defies our current understanding of climate regulation via the silicate weathering feedback, and hints at a fundamentally altered carbon and silica cycle. Here, we propose that the development of widespread marine anoxia and Si-rich conditions, linked to the collapse of the biological silica factory, warming, and increased weathering, was capable of trapping Earth’s system within a hyperthermal by enhancing ocean-atmosphere CO2recycling via authigenic clay formation. While solid-Earth degassing may have acted as a trigger, subsequent biotic feedbacks likely exacerbated and prolonged the environmental crisis. This refined view of the carbon-silica cycle highlights that the ecological success of siliceous organisms exerts a potentially significant influence on Earth’s climate regime.
A randomized placebo-controlled clinical trial for pharmacological activation of BCAA catabolism in patients with type 2 diabetes
Authors: Vanweert Froukje , Neinast Michael , Tapia Edmundo Erazo , van de Weijer Tineke , Hoeks Joris , Schrauwen-Hinderling Vera B. , Blair Megan C. , Bornstein Marc R. , Hesselink Matthijs K. C. , Schrauwen Patrick , Arany Zoltan , Phielix Esther
Published: June 2022

Elevations in plasma branched-chain amino acid (BCAA) levels associate with insulin resistance and type 2 diabetes (T2D). Pre-clinical models suggest that lowering BCAA levels improve glucose tolerance, but data in humans are lacking. Here, we used sodium phenylbutyrate (NaPB), an accelerator of BCAA catabolism, as tool to lower plasma BCAA levels in patients with T2D, and evaluate its effect on metabolic health. This trial (NetherlandsTrialRegister: NTR7426) had a randomized, placebo-controlled, double-blind cross-over design and was performed in the Maastricht University Medical Center (MUMC+), the Netherlands, between February 2019 and February 2020. Patients were eligible for the trial if they were 40–75years, BMI of 25–38 kg/m², relatively well-controlled T2D (HbA1C < 8.5%) and treated with oral glucose-lowering medication. Eighteen participants were randomly assigned to receive either NaPB 4.8 g/m²/day and placebo for 2 weeks via controlled randomization and sixteen participants completed the study. The primary outcome was peripheral insulin sensitivity. Secondary outcomes were ex vivo muscle mitochondrial oxidative capacity, substrate oxidation and ectopic fat accumulation. Fasting blood samples were collected to determine levels of BCAA, their catabolic intermediates, insulin, triglycerides, free fatty acids (FFA) and glucose. NaPB led to a robust 27% improvement in peripheral insulin sensitivity compared to placebo (ΔRd:13.2 ± 1.8 vs. 9.6 ± 1.8 µmol/kg/min, p = 0.02). This was paralleled by an improvement in pyruvate-driven muscle mitochondrial oxidative capacity and whole-body insulin-stimulated carbohydrate oxidation, and a reduction in plasma BCAA and glucose levels. No effects were observed on levels of insulin, triglycerides and FFA, neither did fat accumulation in muscle and liver change. No adverse events were reported. These data establish the proof-of-concept in humans that modulating the BCAA oxidative pathway may represent a potential treatment strategy for patients with T2D.
Complex regulation of Gephyrin splicing is a determinant of inhibitory postsynaptic diversity
Authors: Dos Reis Raphaël , Kornobis Etienne , Pereira Alyssa , Tores Frederic , Carrasco Judit , Gautier Candice , Jahannault-Talignani Céline , Nitschké Patrick , Muchardt Christian , Schlosser Andreas , Maric Hans Michael , Ango Fabrice , Allemand Eric
Published: June 2022

Gephyrin (GPHN) regulates the clustering of postsynaptic components at inhibitory synapses and is involved in pathophysiology of neuropsychiatric disorders. Here, we uncover an extensive diversity of GPHN transcripts that are tightly controlled by splicing during mouse and human brain development. Proteomic analysis reveals at least a hundred isoforms of GPHN incorporated at inhibitory Glycine and gamma-aminobutyric acid A receptors containing synapses. They exhibit different localization and postsynaptic clustering properties, and altering the expression level of one isoform is sufficient to affect the number, size, and density of inhibitory synapses in cerebellar Purkinje cells. Furthermore, we discovered that splicing defects reported in neuropsychiatric disorders are carried by multiple alternative GPHN transcripts, demonstrating the need for a thorough analysis of the GPHN transcriptome in patients. Overall, we show that alternative splicing of GPHN is an important genetic variation to consider in neurological diseases and a determinant of the diversity of postsynaptic inhibitory synapses.
Peptide fusion improves prime editing efficiency
Authors: Velimirovic Minja , Zanetti Larissa C. , Shen Max W. , Fife James D. , Lin Lin , Cha Minsun , Akinci Ersin , Barnum Danielle , Yu Tian , Sherwood Richard I.
Published: June 2022

Prime editing enables search-and-replace genome editing but is limited by low editing efficiency. We present a high-throughput approach, the Peptide Self-Editing sequencing assay (PepSEq), to measure how fusion of 12,000 85-amino acid peptides influences prime editing efficiency. We show that peptide fusion can enhance prime editing, prime-enhancing peptides combine productively, and a top dual peptide-prime editor increases prime editing significantly in multiple cell lines across dozens of target sites. Top prime-enhancing peptides function by increasing translation efficiency and serve as broadly useful tools to improve prime editing efficiency.
A spin-crossover framework endowed with pore-adjustable behavior by slow structural dynamics
Authors: Xue Jin-Peng , Hu Yang , Zhao Bo , Liu Zhi-Kun , Xie Jing , Yao Zi-Shuo , Tao Jun
Published: June 2022

Host-guest interactions play critical roles in achieving switchable structures and functionalities in porous materials, but design and control remain challenging. Here, we report a two-dimensional porous magnetic compound, [FeII(prentrz)2PdII(CN)4] (prentrz = (1E,2E)−3-phenyl-N-(4H-1,2,4-triazol-4-yl)prop-2-en-1-imine), which exhibits an atypical pore transformation that directly entangles with a spin state transition in response to water adsorption. In this material, the adsorption-induced, non-uniform pedal motion of the axial prentrz ligands and the crumpling/unfolding of the layer structure actuate a reversible narrow quasi-discrete pore (nqp) to large channel-type pore (lcp) change that leads to a pore rearrangement associated with simultaneous pore opening and closing. The unusual pore transformation results in programmable adsorption in which the lcp structure type must be achieved first by the long-time exposure of the nqp structure type in a steam-saturated atmosphere to accomplish the gate-opening adsorption. The structural transformation is accompanied by a variation in the spin-crossover (SCO) property of FeII, i.e., two-step SCO with a large plateau for the lcp phase and two-step SCO with no plateau for the nqp phase. The unusual adsorption-induced pore rearrangement and the related SCO property offer a way to design and control the pore structure and physical properties of dynamic frameworks.
X-ray computed microtomography datasets for osteogenic nanofibrous coated titanium implants
Authors: Das Siddhartha , Dholam Kanchan , Gurav Sandeep , Bendale Kiran , Ingle Arvind , Mohanty Bhabani , Chaudhari Pradip , Bellare Jayesh R.
Published: June 2022

Surface modifications of titanium implant influences the quality of osseointegration and are associated with favourable treatment prognosis in orthopaedic and cranio-maxillofacial cases. Hence, unlike previous works, the peri-implant region details of our novel osteogenic nanofibrous coated implants placed in rabbits (n = 6 + 1) were recorded over a 12-week period using a micro-CT imaging system. In this unique contribution, we have created a computed tomography (CT) library of rabbit’s tibiae anatomy with osteogenic nanofibrous coated/uncoated implants and are introductory useful assets for investigating the correlation between osteogenic nanofibers coated implants and its effect on improved osseointegration. Apart from using this CT dataset to conduct serial 2D image studies, three-dimensional (3D) reconstructions, assessing segmentation algorithms and developing adequate image quantitation tools, there may be positive applications of these in comparative investigations of similar or related preclinical as well as future clinical studies, further design planning, development etc. required for evolution of implants beyond the present state of art.
REFLACX, a dataset of reports and eye-tracking data for localization of abnormalities in chest x-rays
Authors: Bigolin Lanfredi Ricardo , Zhang Mingyuan , Auffermann William F. , Chan Jessica , Duong Phuong-Anh T. , Srikumar Vivek , Drew Trafton , Schroeder Joyce D. , Tasdizen Tolga
Published: June 2022

Deep learning has shown recent success in classifying anomalies in chest x-rays, but datasets are still small compared to natural image datasets. Supervision of abnormality localization has been shown to improve trained models, partially compensating for dataset sizes. However, explicitly labeling these anomalies requires an expert and is very time-consuming. We propose a potentially scalable method for collecting implicit localization data using an eye tracker to capture gaze locations and a microphone to capture a dictation of a report, imitating the setup of a reading room. The resulting REFLACX (Reports and Eye-Tracking Data for Localization of Abnormalities in Chest X-rays) dataset was labeled across five radiologists and contains 3,032 synchronized sets of eye-tracking data and timestamped report transcriptions for 2,616 chest x-rays from the MIMIC-CXR dataset. We also provide auxiliary annotations, including bounding boxes around lungs and heart and validation labels consisting of ellipses localizing abnormalities and image-level labels. Furthermore, a small subset of the data contains readings from all radiologists, allowing for the calculation of inter-rater scores.
Gridded maps of wetlands dynamics over mid-low latitudes for 1980–2020 based on TOPMODEL
Authors: Xi Yi , Peng Shushi , Ducharne Agnès , Ciais Philippe , Gumbricht Thomas , Jimenez Carlos , Poulter Benjamin , Prigent Catherine , Qiu Chunjing , Saunois Marielle , Zhang Zhen
Published: June 2022

Dynamics of global wetlands are closely linked to biodiversity conservation, hydrology, and greenhouse gas emissions. However, long-term time series of global wetland products are still lacking. Using a diagnostic model based on the TOPography-based hydrological MODEL (TOPMODEL), this study produced an ensemble of 28 gridded maps of monthly global/regional wetland extents (with more reliable estimates at mid-low latitudes) for 1980–2020 at 0.25° × 0.25° spatial resolution, calibrated with a combination of four observation-based wetland data and seven gridded soil moisture reanalysis datasets. The gridded dynamic maps of wetlands capture the spatial distributions, seasonal cycles, and interannual variabilities of observed wetland extent well, and also show a good agreement with independent satellite-based terrestrial water storage estimates over wetland areas. The long temporal coverage extending beyond the era of satellite datasets, the global coverage, and the opportunity to provide real-time updates from ongoing soil moisture data make these products helpful for various applications such as analyzing the wetland-related methane emission.
Investigating the turbulent dynamics of small-scale surface fires
Authors: Desai Ajinkya , Goodrick Scott , Banerjee Tirtha
Published: June 2022

High frequency (30 Hz) two-dimensional particle image velocimetry data recorded during a field experiment exploring fire spread from point ignition in hand-spread pine needles under calm ambient wind conditions are analysed in this study. In the initial stages, as the flame spreads approximately radially away from the ignition point in the absence of a preferred wind-forcing direction, it entrains cooler ambient air into the warmer fire core, thereby experiencing a dynamic pressure resistance. The fire-front, comprising a flame that is tilted inward, is surrounded by a region of downdraft. Coherent structures describe the initial shape of the fire-front and its response to local wind shifts while also revealing possible fire-spread mechanisms. Vortex tubes originating outside the fire spiral inward and get stretched thinner at the fire-front leading to higher vorticity there. These tubes comprise circulation structures that induce a radially outward velocity close to the fuel bed, which pushes hot gases outward, thereby causing the fire to spread. Moreover, these circulation structures confirm the presence of counter-rotating vortex pairs that are known to be a key mechanism for fire spread. The axis of the vortex tubes changes its orientation alternately towards and away from the surface of the fuel bed, causing the vortex tubes to be kinked. The strong updraft observed at the location of the fire-front could potentially advect and tilt the kinked vortex tube vertically upward leading to fire-whirl formation. As the fire evolves, its perimeter disintegrates in response to flow instabilities to form smaller fire “pockets”. These pockets are confined to certain points in the flow field that remain relatively fixed for a while and resemble the behavior of a chaotic system in the vicinity of an attractor. Increased magnitudes of the turbulent fluxes of horizontal momentum, computed at certain such fixed points along the fire-front, are symptomatic of irregular fire bursts and help contextualize the fire spread. Most importantly, the time-varying transport terms of the turbulent kinetic energy budget equation computed at adjacent fixed points indicate that local fires along the fire-front primarily interact via the horizontal turbulent transport term.
Optimizing plant density and balancing NPK inputs in combination with innovative fertilizer product for sustainable maize production in North China Plain
Authors: Feyissa Tesema , Zhao Shuaixiang , Ma Hailong , Duan Zhiping , Zhang Weifeng
Published: June 2022

Excessive NPK inputs but low grain yield and high environmental impact are common issues in maize production in North China Plain (NCP). The objective of our study was to test whether a combined strategy of optimizing plant density, balancing NPK input, and innovating one-time fertilizer products could achieve a more sustainable maize production in NCP. Thus, a field experiment was conducted at Luanna County NCP with the treatments of unfertilized control (CK), farmer practice (FP, conventional plant density and NPK input), conventional one-time urea-based coated fertilizer (CF, optimized plant density and NPK input), and five newly designed innovative one-time NPK fertilizers of ammonium sulphate and urea synergy (IF, optimized plant density and NPK input), innovative fertilizer with various additives of urea inhibitors (IF + UI), double inhibitors (IF + DI), micro-organisms (IF + MI), and trace elements (IF + TE). The grain yield, N sustainability indicators (N use efficiency NUE, partial factor productivity of N PFPN, and N surplus), and cost-benefits analysis were examined over the maize growing season of 2020. Results had shown that on average the five innovative fertilizers (IF, IF + UI, IF + DI, IF + MI, and IF + TE) and CF that had optimized plant density and NPK input achieved 13.5%, 98.6%, 105.9%, 37.4% higher yield, PFPN, NUE, net-benefits as well as 207.1% lower N surplus compared with FP respectively. Notably, the innovative fertilizer with various effective additives (IF + UI, IF + DI, IF + MI, and IF + TE) which can be commonly found in the fertilizer market hadn’t resulted in a significant improvement in yield and NUE rather a greater cost and lower net benefits in comparison to IF. In summary, our study highlighted the effectiveness of the combined strategy of optimized plant density, balancing NPK input, and innovative NPK fertiliser on sustainable maize production in NCP, however, the innovative fertilisers with effective additives should be properly selected for better economic benefits.
Development of a robust real-time synchronized data transmission technique from a Magnetic Observatory to an INTERMAGNET GIN
Authors: Potharaju Sai Vijay Kumar , Nelapatla Phani Chandrasekhar
Published: June 2022

This paper presents the step-by-step development and implementation of real-time data transmission from a distant Observatory. Using Python programming language, we have developed an algorithm for automated data transmission of high resolution real-time magnetic data from Choutuppal (CPL) and Hyderabad (HYB), India to INTERMAGNET Edinburgh GIN, with minimal internet services. We have designed a system to transfer the data in a secured and encrypted pattern with SSH keys and save the same dataset in the local server at CSIR-NGRI. Both the Observatories data are transmitted to GIN in real-time with a time frame of less than 300 s. After successfully transmitting real-time 1 min geomagnetic data from CPL and HYB Observatories to Edinburgh GIN, CPL's 1 s real-time data is also initiated and is one of the first Indian observatories to transmit real-time 1 s data to GIN. The details of algorithm development, function libraries and the challenges faced for 1 s and 1 min data transmission at both the Observatories are discussed.