bluuebunny/crossref_metadata_2025 huggingface dataset:
A Different View on Dynamics of Space Curves Geometry
Authors: Tunçer Yılmaz
Published: December 2021

In this study, we define the X-torque curves, $$X-$$

X
-

equilibrium curves, X-moment conservative curves, $$X-$$

X
-

gyroscopic curves as new curves derived from a regular space curve by using the Frenet vectors of a space curve and its position vector, where $$X\in \left\{ T\left( s\right) , N\left( s\right) , B\left( s\right) \right\} $$

X
∈

T

s

,
N

s

,
B

s

and we examine these curves and we give their properties.
America's Wars
Authors: Henriksen Thomas H.
Published: December 2021

The collapse of the Soviet Union ushered in American global hegemony in world affairs. In the post-Cold War period, both Democrat and Republican governments intervened, fought insurgencies, and changed regimes. In America's Wars, Thomas Henriksen explores how America tried to remake the world by militarily invading a host of nations beset with civil wars, ethnic cleansing, brutal dictators, and devastating humanitarian conditions. The immediate post-Cold War years saw the United States carrying out interventions in the name of Western-style democracy, humanitarianism, and liberal internationalism in Panama, Somalia, Haiti, Bosnia and Kosovo. Later, the 9/11 terrorist attacks led America into larger-scale military incursions to defend itself from further assaults by al Qaeda in Afghanistan and from perceived nuclear arms in Iraq, while fighting small-footprint conflicts in Africa, Asia, and Arabia. This era is coming to an end with the resurgence of great power rivalry and rising threats from China and Russia.
Radiometric analysis of digitized Z-scope records in archival radar sounding film
Authors: Schroeder Dustin M. , Broome Anna L. , Conger Annabel , Lynch Acacia , Mackie Emma J. , Tarzona Angelo
Published: December 2021

The earliest airborne geophysical campaigns over Antarctica and Greenland in the 1960s and 1970s collected ice penetrating radar data on 35 mm optical film. Early subglacial topographic and englacial stratigraphic analyses of these data were foundational to the field of radioglaciology. Recent efforts to digitize and release these data have resulted in geometric and ice-thickness analysis that constrain subsurface change over multiple decades but stop short of radiometric interpretation. The primary challenge for radiometric analysis is the poorly-characterized compression applied to Z-scope records and the sparse sampling of A-scope records. Here, we demonstrate the information richness and radiometric interpretability of Z-scope records. Z-scope pixels have uncalibrated fast-time, slow-time, and intensity scales. We develop approaches for mapping each of these scales to physical units (microseconds, seconds, and signal to noise ratio). We then demonstrate the application of this calibration and analysis approach to a flight in the interior of East Antarctica with subglacial lakes and to a reflight of an East Antarctic ice shelf that was observed by both archival and modern radar. These results demonstrate the potential use of Z-scope signals to extend the baseline of radiometric observations of the subsurface by decades.
How Open Lists Undermine the Electoral Support of Cohesive Parties
Authors: Bräuninger Thomas , Däubler Thomas , Huber Robert , Rudolph Lukas
Published: December 2021

How does ballot structure affect party choice? We argue that open lists undermine the electoral support of cohesive parties, to the benefit of internally divided parties. We conduct a survey-embedded experiment in the aftermath of the European migrant crisis, presenting German voters with real parties but fictitious politicians. A crossover design varies ballot type and exposure to candidate positions on immigration. We find that the internally divided Christian Democrats gain votes at the expense of the cohesive Alternative for Germany when open lists are used and candidate positions are known. For individuals who are equally attracted to both parties, switching is most likely if their immigration preferences lie near the midpoint between the two parties. Overall, our analysis establishes conditions under which ballot structure can affect the electoral performance of parties in general, and that of the populist right in particular.
Iron deficiency and internalizing symptom severity in unmedicated adolescents: a pilot study
Authors: Abbas Malak , Gandy Kellen , Salas Ramiro , Devaraj Sridevi , Calarge Chadi A.
Published: December 2021

Background

Iron plays a key role in a broad set of metabolic processes. Iron deficiency is the most common nutritional deficiency in the world, but its neuropsychiatric implications in adolescents have not been examined.

Methods

Twelve- to 17-year-old unmedicated females with major depressive or anxiety disorders or with no psychopathology underwent a comprehensive psychiatric assessment for this pilot study. A T1-weighted magnetic resonance imaging scan was obtained, segmented using Freesurfer. Serum ferritin concentration (sF) was measured. Correlational analyses examined the association between body iron stores, psychiatric symptom severity, and basal ganglia volumes, accounting for confounding variables.

Results

Forty females were enrolled, 73% having a major depressive and/or anxiety disorder, 35% with sF < 15 ng/mL, and 50% with sF < 20 ng/mL. Serum ferritin was inversely correlated with both anxiety and depressive symptom severity (r = −0.34, p < 0.04 and r = −0.30, p < 0.06, respectively). Participants with sF < 15 ng/mL exhibited more severe depressive and anxiety symptoms as did those with sF < 20 ng/mL. Moreover, after adjusting for age and total intracranial volume, sF was inversely associated with left caudate (Spearman's r = −0.46, p < 0.04), left putamen (r = −0.58, p < 0.005), and right putamen (r = −0.53, p < 0.01) volume.

Conclusions

Brain iron may become depleted at a sF concentration higher than the established threshold to diagnose iron deficiency (i.e. 15 ng/mL), potentially disrupting brain maturation and contributing to the emergence of internalizing disorders in adolescents.
Familial clustering of psychiatric disorders and low IQ
Authors: Weiser Mark , Frenkel Or , Fenchel Daphna , Tzur Dorit , Sandin Sven , Janecka Magdalena , Levi Linda , Davidson Michael , Laor Lucian , Fruchter Eyal , Reichenberg Abraham
Published: December 2021

Background

Although the ICD and DSM differentiate between different psychiatric disorders, these often share symptoms, risk factors, and treatments. This was a population-based, case–control, sibling study examining familial clustering of all psychiatric disorders and low IQ, using data from the Israel Draft-Board Registry on all Jewish adolescents assessed between 1998 and 2014.

Methods

We identified all cases with autism spectrum disorder (ASD, N = 2128), severe intellectual disability (ID, N = 9572), attention-deficit hyperactive disorder (ADHD) (N = 3272), psychotic (N = 7902), mood (N = 9704), anxiety (N = 10 606), personality (N = 24 816), or substance/alcohol abuse (N = 791) disorders, and low IQ (⩾2 SDs below the population mean, N = 31 186). Non-CNS control disorders were adolescents with Type-1 diabetes (N = 2427), hernia (N = 29 558) or hematological malignancies (N = 931). Each case was matched with 10 age-matched controls selected at random from the Draft-Board Registry, with replacement, and for each case and matched controls, we ascertained all full siblings. The main outcome measure was the relative recurrence risk (RRR) of the sibling of a case having the same (within-disorder RRR) or a different (across-disorder RRR) disorder.

Results

Within-disorder RRRs were increased for all diagnostic categories, ranging from 11.53 [95% confidence interval (CI): 9.23–14.40] for ASD to 2.93 (95% CI: 2.80–3.07) for personality disorders. The median across-disorder RRR between any pair of psychiatric disorders was 2.16 (95% CI: 1.45–2.43); the median RRR between low IQ and any psychiatric disorder was 1.37 (95% CI: 0.93–1.98). There was no consistent increase in across-disorder RRRs between the non-CNS disorders and psychiatric disorders and/or low IQ.

Conclusion

These large population-based study findings suggest shared etiologies among most psychiatric disorders, and low IQ.
Die Wirkung von Hypnose auf Parameter des Immunsystems
Authors: Karrasch Sarah , Bongartz Walter , Gumpp Anja M. , Kolassa Iris-Tatjana
Published: December 2021

Zusammenfassung. Theoretischer Hintergrund: Mit Hypnose können positive immunmodulierende und therapeutische Effekte bei psychischen sowie somatischen stress-assoziierten Erkrankungen erzielt werden. Fragestellung: Diese Arbeit beschäftigt sich mit immunologischen Veränderungen durch Hypnose und zeigt potentielle zukünftige Forschungsfelder zu biomolekularen Wirkfaktoren von Hypnose auf. Methode: Es werden empirische Befunde zur Wirkung von Hypnose auf Parameter des Immunsystems zusammengefasst. Ergebnisse: Hypnose führt zu einer Anpassungsreaktion des Immunsystems in Form von Veränderungen in der Anzahl von Immunzellen und Zytokinen. Schlussfolgerung: Ein spannendes neues Forschungsfeld liegt in der Untersuchung der Wirkmechanismen von Hypnose auf das Immunsystem sowie dessen Interaktion mit dem Stresssystem und dem Energiemetabolismus.
Evaluation einer Mehrfamiliengruppe für Patient_innen mit einer Borderline-Persönlichkeitsstörung und ihre Angehörigen
Authors: Kemper Madita , Gunia Hans , Haberstroh Julia
Published: December 2021

Zusammenfassung. Hintergrund. Familiäre Konflikte und dysfunktionale Verhaltensweisen spielen eine entscheidende Rolle bei der Entstehung und Aufrechterthaltung von Borderline-Persönlichkeitsstörungen (BPS). Auf der Grundlage der Dialektisch-Behavioralen Therapie (DBT) berücksichtigte Alan Fruzzetti die genannten Faktoren in einem transaktionalen Entstehungmodell. Um BPS-Betroffenen und deren Angehörigen Strategien für eine funktionalere Emotions- und Interaktionsbewältigung an die Hand zu geben, entwickelte Alan Fruzzetti DBT-Familien-Skills. Fragestellung. Die Wirksamkeit dieser Fertigkeiten als therapeutische Intervention im Rahmen eines Mehrfamiliensettings wurde im Rahmen der vorliegenden Pilotstudie evaluiert. Methode. Mittels Tagebuch- und Sitzungsabfragen wurden prozessuale Daten der psychischen Beanspruchung und Anwendungshäufigkeit von DBT-Familien-Skills (AFS) erhoben. Ergebnisse. Via Trendanalysen konnten Hinweise auf hypothesenkonforme Beanspruchungsreduktionen und eine Zunahme der AFS über den zeitlichen Gruppenverlauf bei BPS-Betroffenen und Angehörigen identifiziert werden. Schlussfolgerung. Die Ergebnisse der Pilotstudie liefern erste Hinweise, dass die in einem Mehrfamilienformat angebotenen DBT-Familien-Skills zu einer Reduktion der psychischen Beanspruchung der BPS-Betroffenen und Angehörigen beitragen.
Will Anthropogenic Warming Increase Evapotranspiration? Examining Irrigation Water Demand Implications of Climate Change in California
Authors: Vahmani P. , Jones A. D. , Li D.
Published: December 2021

Climate modeling studies and observations do not fully agree on the implications of anthropogenic warming for evapotranspiration (ET), a major component of the water cycle and driver of irrigation water demand. Here, we use California as a testbed to assess the ET impacts of changing atmospheric conditions induced by climate change on irrigated systems. Our analysis of irrigated agricultural and urban regions shows that warmer atmospheric temperatures have minimal implications for ET rates and irrigation water demands—about one percent change per degree Celsius warming (∼1% °C−1). By explicitly modeling irrigation, we control for the confounding effect of climate‐driven soil moisture changes and directly estimate water demand implications. Our attribution analysis of the drivers of ET response to global anthropogenic warming shows that as the atmospheric temperature and vapor pressure deficit depart from the ideal conditions for transpiration, regulation of stomata resistance by stressed vegetation almost completely offsets the expected increase in ET rates that would otherwise result from abiotic processes alone. We further show that anthropogenic warming of the atmosphere has minimal implications for mean relative humidity (<1.7% °C−1) and the surface available energy (<0.2% °C−1), which are critical drivers of ET. This study corroborates the growing evidence that plant physiological changes moderate the degree to which changes in potential ET are realized as actual ET.
Massive Multi‐Mission Statistical Study and Analytical Modeling of the Earth's Magnetopause: 4. On the Near‐Cusp Magnetopause Indentation
Authors: Nguyen G. , Aunai N. , Michotte de Welle B. , Jeandet A. , Lavraud B. , Fontaine D.
Published: December 2021

The shape and location of the magnetopause current sheet in the near‐cusp region is still a debated question. Over time, several observations led to contradictory conclusions regarding the presence of an indentation of the magnetopause in that region. As a result several empirical models consider the surface is indented in that region, while some others do not. To tackle this issue, we fit a total of 17,230 magnetopause crossings to various indented and non‐indented analytical models. The results show that while all models describe the magnetopause position and shape equivalently far from the cusp region, the non‐indented version over‐estimate the radial position of the near‐cusp magnetopause. Among indented models, we show that the one designed from non‐linearmagneto hydrodynamic simulations fits well the near‐cusp magnetopause location, while the other underestimate its position probably because their design was possibly based on magnetopause crossing catalogs that contain cusp inner boundary crossings.
Representing Global Soil Erosion and Sediment Flux in Earth System Models
Authors: Tan Zeli , Leung L. Ruby , Li Hong‐Yi , Cohen Sagy
Published: December 2021

Soil erosion produces enormous amounts of sediment, carbon, and nutrient fluxes from land to rivers, thus playing crucial roles in global biogeochemical cycles and food security. To predict soil erosion in the context of climate and land use changes, we explicitly parameterize cropland management actions (i.e., irrigation, conserved agriculture, and crop residue management) and geological factors (i.e., lithology and glacier) in the Energy Exascale Earth System Model (E3SM) soil erosion module. The erosion model is calibrated using a global‐scale regionalized parameter calibration method. The spatial variabilities of the modeled and the Revised Universal Soil Loss Equation (RUSLE) based benchmark soil erosion are consistent across vegetation, climate and soil properties. Compared with independent data, our model shows a bias reduction in 59% of the observations relative to the RUSLE‐based soil erosion, with 53% of the bias reduction exceeding 50%. This improvement is mainly due to a better representation of the topographic effect on soil erosion. Our results indicate that conserved agriculture practices have effectively reduced soil erosion in cropland by over 25% in the United States and Argentina. In contrast, irrigation has increased soil erosion in many Asian countries. For upland sediment flux, our model is consistent with the WBMsed benchmark data in inter‐basin variability but could be more skillful in simulating intra‐basin variability because it couples soil erosion and sediment flux explicitly. The developed model provides useful skills for more realistic predictions of soil erosion and river sediment dynamics under environmental changes.
Use of Abstraction and Discharge Data to Improve the Performance of a National‐Scale Hydrological Model
Authors: Rameshwaran Ponnambalam , Bell Victoria A. , Brown Matthew J. , Davies Helen N. , Kay Alison L. , Rudd Alison C. , Sefton Catherine
Published: December 2021

Across the UK, water abstracted from ground, surface, and tidal stores is regulated through a system of licenses to protect both the sources and the environment. Similar permits are required for discharging wastewater to rivers or onto the ground. These abstractions and discharges can have a significant impact on UK Rivers, but measurements are not readily available, which discourages their use in hydrological models of river flows. However, these very unique data sets provide a means to improve the performance of spatially distributed hydrological models, particularly during periods when abstraction regulations change and at ungauged river locations. To demonstrate this, point source abstraction and discharge measurements across England have been transformed into 1 × 1 km resolution gridded data and used with an enhanced formulation of the Grid‐to‐Grid (G2G) hydrological model where these processes are mathematically represented. A comparison of G2G‐simulated and gauged river flows for 605 catchments across England between 1999 and 2014 indicates that model simulation of river flows is generally improved at gauged locations downstream of abstraction/discharge sites. The main improvement is in the simulation of low flows, for which the median performance is improved by 10.7%, however, the impact on simulation of high river flows is more modest (1.5% improvement). These results demonstrate the potential gains available to the international hydrological and land‐surface modeling community from using records of actual water use (where available) in models, in place of more widely used national statistics.
Cytoplasmic innate immune sensing by the caspase-4 non-canonical inflammasome promotes cellular senescence
Authors: Fernández-Duran Irene , Quintanilla Andrea , Tarrats Núria , Birch Jodie , Hari Priya , Millar Fraser R. , Lagnado Anthony B. , Smer-Barreto Vanessa , Muir Morwenna , Brunton Valerie G. , Passos João F. , Acosta Juan Carlos
Published: December 2021

Cytoplasmic recognition of microbial lipopolysaccharides (LPS) in human cells is elicited by the caspase-4 and caspase-5 noncanonical inflammasomes, which induce a form of inflammatory cell death termed pyroptosis. Here we show that LPS-mediated activation of caspase-4 also induces a stress response promoting cellular senescence, which is dependent on the caspase-4 substrate gasdermin-D and the tumor suppressor p53. Furthermore, we found that the caspase-4 noncanonical inflammasome is induced and assembled in response to oncogenic RAS signaling during oncogene-induced senescence (OIS). Moreover, targeting caspase-4 expression in OIS showed its critical role in the senescence-associated secretory phenotype and the cell cycle arrest induced in cellular senescence. Finally, we observed that caspase-4 induction occurs in vivo in mouse models of tumor suppression and ageing. Altogether, we are showing that cellular senescence is induced by cytoplasmic LPS recognition by the noncanonical inflammasome and that this pathway is conserved in the cellular response to oncogenic stress.
Secondary organic aerosol association with cardiorespiratory disease mortality in the United States
Authors: Pye Havala O. T. , Ward-Caviness Cavin K. , Murphy Ben N. , Appel K. Wyat , Seltzer Karl M.
Published: December 2021

Fine particle pollution, PM2.5, is associated with increased risk of death from cardiorespiratory diseases. A multidecadal shift in the United States (U.S.) PM2.5composition towards organic aerosol as well as advances in predictive algorithms for secondary organic aerosol (SOA) allows for novel examinations of the role of PM2.5components on mortality. Here we show SOA is strongly associated with county-level cardiorespiratory death rates in the U.S. independent of the total PM2.5mass association with the largest associations located in the southeastern U.S. Compared to PM2.5, county-level variability in SOA across the U.S. is associated with 3.5× greater per capita county-level cardiorespiratory mortality. On a per mass basis, SOA is associated with a 6.5× higher rate of mortality than PM2.5, and biogenic and anthropogenic carbon sources both play a role in the overall SOA association with mortality. Our results suggest reducing the health impacts of PM2.5requires consideration of SOA.
Predicting fault slip via transfer learning
Authors: Wang Kun , Johnson Christopher W. , Bennett Kane C. , Johnson Paul A.
Published: December 2021

Data-driven machine-learning for predicting instantaneous and future fault-slip in laboratory experiments has recently progressed markedly, primarily due to large training data sets. In Earth however, earthquake interevent times range from 10’s-100’s of years and geophysical data typically exist for only a portion of an earthquake cycle. Sparse data presents a serious challenge to training machine learning models for predicting fault slip in Earth. Here we describe a transfer learning approach using numerical simulations to train a convolutional encoder-decoder that predicts fault-slip behavior in laboratory experiments. The model learns a mapping between acoustic emission and fault friction histories from numerical simulations, and generalizes to produce accurate predictions of laboratory fault friction. Notably, the predictions improve by further training the model latent space using only a portion of data from a single laboratory earthquake-cycle. The transfer learning results elucidate the potential of using models trained on numerical simulations and fine-tuned with small geophysical data sets for potential applications to faults in Earth.
Bedform segregation and locking increase storage of natural and synthetic particles in rivers
Authors: Dallmann J. , Phillips C. B. , Teitelbaum Y. , Saavedra Cifuentes Edwin Y. , Sund N. , Schumer R. , Arnon S. , Packman A. I.
Published: December 2021

While the ecological significance of hyporheic exchange and fine particle transport in rivers is well established, these processes are generally considered irrelevant to riverbed morphodynamics. We show that coupling between hyporheic exchange, suspended sediment deposition, and sand bedform motion strongly modulates morphodynamics and sorts bed sediments. Hyporheic exchange focuses fine-particle deposition within and below mobile bedforms, which suppresses bed mobility. However, deposited fines are also remobilized by bedform motion, providing a mechanism for segregating coarse and fine particles in the bed. Surprisingly, two distinct end states emerge from the competing interplay of bed stabilization and remobilization: a locked state in which fine particle deposition completely stabilizes the bed, and a dynamic equilibrium in which frequent remobilization sorts the bed and restores mobility. These findings demonstrate the significance of hyporheic exchange to riverbed morphodynamics and clarify how dynamic interactions between coarse and fine particles produce sedimentary patterns commonly found in rivers.
Single dose of chimeric dengue-2/Zika vaccine candidate protects mice and non-human primates against Zika virus
Authors: Baldwin Whitney R. , Giebler Holli A. , Stovall Janae L. , Young Ginger , Bohning Kelly J. , Dean Hansi J. , Livengood Jill A. , Huang Claire Y.-H.
Published: December 2021

The development of a safe and effective Zika virus (ZIKV) vaccine has become a global health priority since the widespread epidemic in 2015-2016. Based on previous experience in using the well-characterized and clinically proven dengue virus serotype-2 (DENV-2) PDK-53 vaccine backbone for live-attenuated chimeric flavivirus vaccine development, we developed chimeric DENV-2/ZIKV vaccine candidates optimized for growth and genetic stability in Vero cells. These vaccine candidates retain all previously characterized attenuation phenotypes of the PDK-53 vaccine virus, including attenuation of neurovirulence for 1-day-old CD-1 mice, absence of virulence in interferon receptor-deficient mice, and lack of transmissibility in the main mosquito vectors. A single DENV-2/ZIKV dose provides protection against ZIKV challenge in mice and rhesus macaques. Overall, these data indicate that the ZIKV live-attenuated vaccine candidates are safe, immunogenic and effective at preventing ZIKV infection in multiple animal models, warranting continued development.
Mechanisms of SARS-CoV-2 neutralization by shark variable new antigen receptors elucidated through X-ray crystallography
Authors: Ubah Obinna C. , Lake Eric W. , Gunaratne Gihan S. , Gallant Joseph P. , Fernie Marie , Robertson Austin J. , Marchant Jonathan S. , Bold Tyler D. , Langlois Ryan A. , Matchett William E. , Thiede Joshua M. , Shi Ke , Yin Lulu , Moeller Nicholas H. , Banerjee Surajit , Ferguson Laura , Kovaleva Marina , Porter Andrew J. , Aihara Hideki , LeBeau Aaron M. , Barelle Caroline J.
Published: December 2021

Single-domain Variable New Antigen Receptors (VNARs) from the immune system of sharks are the smallest naturally occurring binding domains found in nature. Possessing flexible paratopes that can recognize protein motifs inaccessible to classical antibodies, VNARs have yet to be exploited for the development of SARS-CoV-2 therapeutics. Here, we detail the identification of a series of VNARs from a VNAR phage display library screened against the SARS-CoV-2 receptor binding domain (RBD). The ability of the VNARs to neutralize pseudotype and authentic live SARS-CoV-2 virus rivalled or exceeded that of full-length immunoglobulins and other single-domain antibodies. Crystallographic analysis of two VNARs found that they recognized separate epitopes on the RBD and had distinctly different mechanisms of virus neutralization unique to VNARs. Structural and biochemical data suggest that VNARs would be effective therapeutic agents against emerging SARS-CoV-2 mutants, including the Delta variant, and coronaviruses across multiple phylogenetic lineages. This study highlights the utility of VNARs as effective therapeutics against coronaviruses and may serve as a critical milestone for nearing a paradigm shift of the greater biologic landscape.
Stochastic fluctuations of bosonic dark matter
Authors: Centers Gary P. , Blanchard John W. , Conrad Jan , Figueroa Nataniel L. , Garcon Antoine , Gramolin Alexander V. , Kimball Derek F. Jackson , Lawson Matthew , Pelssers Bart , Smiga Joseph A. , Sushkov Alexander O. , Wickenbrock Arne , Budker Dmitry , Derevianko Andrei
Published: December 2021

Numerous theories extending beyond the standard model of particle physics predict the existence of bosons that could constitute dark matter. In the standard halo model of galactic dark matter, the velocity distribution of the bosonic dark matter field defines a characteristic coherence timeτc. Until recently, laboratory experiments searching for bosonic dark matter fields have been in the regime where the measurement timeTsignificantly exceedsτc, so null results have been interpreted by assuming a bosonic field amplitude Φ0fixed by the average local dark matter density. Here we show that experiments operating in theT ≪ τcregime do not sample the full distribution of bosonic dark matter field amplitudes and therefore it is incorrect to assume a fixed value of Φ0when inferring constraints. Instead, in order to interpret laboratory measurements (even in the event of a discovery), it is necessary to account for the stochastic nature of such a virialized ultralight field. The constraints inferred from several previous null experiments searching for ultralight bosonic dark matter were overestimated by factors ranging from 3 to 10 depending on experimental details, model assumptions, and choice of inference framework.
The long non-coding RNA landscape of Candida yeast pathogens
Authors: Hovhannisyan Hrant , Gabaldón Toni
Published: December 2021

Long non-coding RNAs (lncRNAs) constitute a poorly studied class of transcripts with emerging roles in key cellular processes. Despite efforts to characterize lncRNAs across a wide range of species, these molecules remain largely unexplored in most eukaryotic microbes, including yeast pathogens of the Candida clade. Here, we analyze thousands of publicly available sequencing datasets to infer and characterize the lncRNA repertoires of five major Candida pathogens: Candida albicans, Candida tropicalis, Candida parapsilosis, Candida auris and Candida glabrata. Our results indicate that genomes of these species encode hundreds of lncRNAs that show levels of evolutionary constraint intermediate between those of intergenic genomic regions and protein-coding genes. Despite their low sequence conservation across the studied species, some lncRNAs are syntenic and are enriched in shared sequence motifs. We find co-expression of lncRNAs with certain protein-coding transcripts, hinting at potential functional associations. Finally, we identify lncRNAs that are differentially expressed during infection of human epithelial cells for four of the studied species. Our comprehensive bioinformatic analyses of Candida lncRNAs pave the way for future functional characterization of these transcripts.
Development of multivalent mRNA vaccine candidates for seasonal or pandemic influenza
Authors: Chivukula Sudha , Plitnik Timothy , Tibbitts Timothy , Karve Shrirang , Dias Anusha , Zhang Donghui , Goldman Rebecca , Gopani Hardip , Khanmohammed Asad , Sarode Ashish , Cooper Dustin , Yoon Heesik , Kim Younghoon , Yan Yanhua , Mundle Sophia T. , Groppo Rachel , Beauvais Adrien , Zhang Jinrong , Anosova Natalie G. , Lai Charles , Li Lu , Ulinski Gregory , Piepenhagen Peter , DiNapoli Joshua , Kalnin Kirill V. , Landolfi Victoria , Swearingen Ron , Fu Tong-Ming , DeRosa Frank , Casimiro Danilo
Published: December 2021

Recent approval of mRNA vaccines for emergency use against COVID-19 is likely to promote rapid development of mRNA-based vaccines targeting a wide range of infectious diseases. Compared to conventional approaches, this vaccine modality promises comparable potency while substantially accelerating the pace of development and deployment of vaccine doses. Already demonstrated successfully for single antigen vaccines such as for COVID-19, this technology could be optimized for complex multi-antigen vaccines. Herein, utilizing multiple influenza antigens, we demonstrated the suitability of the mRNA therapeutic (MRT) platform for such applications. Seasonal influenza vaccines have three or four hemagglutinin (HA) antigens of different viral subtypes. In addition, influenza neuraminidase (NA), a tetrameric membrane protein, is identified as an antigen that has been linked to protective immunity against severe viral disease. We detail the efforts in optimizing formulations of influenza candidates that use unmodified mRNA encoding full-length HA or full-length NA encapsulated in lipid nanoparticles (LNPs). HA and NA mRNA-LNP formulations, either as monovalent or as multivalent vaccines, induced strong functional antibody and cellular responses in non-human primates and such antigen-specific antibody responses were associated with protective efficacy against viral challenge in mice.
A light-fuelled nanoratchet shifts a coupled chemical equilibrium
Authors: Kathan Michael , Crespi Stefano , Thiel Niklas O. , Stares Daniel L. , Morsa Denis , de Boer John , Pacella Gianni , van den Enk Tobias , Kobauri Piermichele , Portale Giuseppe , Schalley Christoph A. , Feringa Ben L.
Published: December 2021

Biological molecular machines enable chemical transformations, assembly, replication and motility, but most distinctively drive chemical systems out of-equilibrium to sustain life1,2. In such processes, nanometre-sized machines produce molecular energy carriers by driving endergonic equilibrium reactions. However, transforming the work performed by artificial nanomachines3–5into chemical energy remains highly challenging. Here, we report a light-fuelled small-molecule ratchet capable of driving a coupled chemical equilibrium energetically uphill. By bridging two imine6–9macrocycles with a molecular motor10,11, the machine forms crossings and consequently adopts several distinct topologies by either a thermal (temporary bond-dissociation) or photochemical (unidirectional rotation) pathway. While the former will relax the machine towards the global energetic minimum, the latter increases the number of crossings in the system above the equilibrium value. Our approach provides a blueprint for coupling continuous mechanical motion performed by a molecular machine with a chemical transformation to reach an out-of-equilibrium state.
Dynamic X-ray elastography using a pulsed photocathode source
Authors: Kamezawa Chika , Cramer Avilash , Krull Wolfgang , Yashiro Wataru , Hyodo Kazuyuki , Gupta Rajiv
Published: December 2021

X-ray absorption of breast cancers and surrounding healthy tissue can be very similar, a situation that sometimes leads to missed cancers or false-positive diagnoses. To increase the accuracy of mammography and breast tomosynthesis, we describe dynamic X-ray elastography using a novel pulsed X-ray source. This new imaging modality provides both absorption and mechanical properties of the imaged material. We use a small acoustic speaker to vibrate the sample while a synchronously pulsed cold cathode X-ray source images the mechanical deformation. Using these stroboscopic images, we derive two-dimensional stiffness maps of the sample in addition to the conventional X-ray image. In a breast phantom composed of ZrO2 powder embedded in gel, dynamic elastography derived stiffness maps were able to discriminate a hard inclusion from surrounding material with a contrast-to-noise ratio (CNR) of 4.5. The CNR on the corresponding absorption image was 1.1. This demonstrates the feasibility of dynamic X-ray elastography with a synchronously pulsed X-ray source.
Harmonic convergence coordinates swarm mating by enhancing mate detection in the malaria mosquito Anopheles gambiae
Authors: Garcia Castillo Stefano S. , Pritts Kevin S. , Krishnan Raksha S. , Harrington Laura C. , League Garrett P.
Published: December 2021

The mosquitoAnopheles gambiaeis a major African malaria vector, transmitting parasites responsible for significant mortality and disease burden. Although flight acoustics are essential to mosquito mating and present promising alternatives to insecticide-based vector control strategies, there is limited data on mosquito flight tones during swarming. Here, for the first time, we present detailed analyses of free-flying male and femaleAn. gambiaeflight tones and their harmonization (harmonic convergence) over a complete swarm sequence. Audio analysis of single-sex swarms showed synchronized elevation of male and female flight tones during swarming. Analysis of mixed-sex swarms revealed additional 50 Hz increases in male and female flight tones due to mating activity. Furthermore, harmonic differences between male and female swarm tones in mixed-sex swarms and in single-sex male swarms with artificial female swarm audio playback indicate that frequency differences of approximately 50 Hz or less at the male second and female third harmonics (M2:F3) are maintained both before and during mating interactions. This harmonization likely coordinates male scramble competition by maintaining ideal acoustic recognition within mating pairs while acoustically masking phonotactic responses of nearby swarming males to mating females. These findings advance our knowledge of mosquito swarm acoustics and provide vital information for reproductive control strategies.
The effect of levosimendan on right ventricular function in patients with heart dysfunction: a systematic review and meta-analysis
Authors: Hu Yaoshi , Wei Zhe , Zhang Chaoyong , Lu Chuanghong , Zeng Zhiyu
Published: December 2021

Levosimendan exerts positive inotropic and vasodilatory effects. Currently, its effects on right heart function remain uncertain. This systematic review and meta-analysis is intended to illustrate the impacts of levosimendan on systolic function of the right heart in patients with heart dysfunction. We systematically searched electronic databases (PubMed, the Cochrane Library, Embase and Web of Science) up to November 30, 2020, and filtered eligible studies that reported the impacts of levosimendan on right heart function. Of these, only studies whose patients suffered from heart dysfunction or pulmonary hypertension were included. Additionally, patients were divided into two groups (given levosimendan or not) in the initial research. Then, RevMan5.3 was used to conduct further analysis. A total of 8 studies comprising 390 patients were included. The results showed that after 24 h of levosimendan, patients’ right ventricular fractional area change [3.17, 95% CI (2.03, 4.32), P < 0.00001], tricuspid annular plane systolic excursion [1.26, 95% CI (0.35, 2.16), P = 0.007] and tricuspid annular peak systolic velocity [0.86, 95% CI (0.41, 1.32), P = 0.0002] were significantly increased compared to the control group. And there is an increasing trend of cardiac output in levosimendan group [1.06, 95% CI (− 0.16, 2.29), P = 0.09 ] .Furthermore, patients’ systolic pulmonary arterial pressure [− 5.57, 95% CI (− 7.60, − 3.54), P < 0.00001] and mean pulmonary arterial pressure [− 1.01, 95% CI (− 1.64, − 0.37), P = 0.002] were both significantly decreased, whereas changes in pulmonary vascular resistance [− 55.88, 95% CI (− 206.57, 94.82), P = 0.47] were not significant. Our study shows that in patients with heart dysfunction, levosimendan improves systolic function of the right heart and decreases the pressure of the pulmonary artery.
Direct pesticide exposure of insects in nature conservation areas in Germany
Authors: Brühl Carsten A. , Bakanov Nikita , Köthe Sebastian , Eichler Lisa , Sorg Martin , Hörren Thomas , Mühlethaler Roland , Meinel Gotthard , Lehmann Gerlind U. C.
Published: December 2021

In Germany, the decline of insect biomass was observed in nature conservation areas in agricultural landscapes. One of the main causal factors discussed is the use of synthetic pesticides in conventional agriculture. In a Germany-wide field study, we collected flying insects using Malaise traps in nature conservation areas adjacent to agricultural land. We used a multi-component chemical trace element analysis to detect 92 common agricultural pesticides in ethanol from insect traps sampled in May and August 2020. In total, residues of 47 current use pesticides were detected, and insect samples were on average contaminated with 16.7 pesticides. Residues of the herbicides metolachlor-S, prosulfocarb and terbuthylazine, and the fungicides azoxystrobin and fluopyram were recorded at all sites. The neonicotinoid thiacloprid was detected in 16 of 21 nature conservation areas, most likely due to final use before an EU-wide ban. A change in residue mixture composition was noticeable due to higher herbicide use in spring and increasing fungicide applications in summer. The number of substances of recorded residues is related to the proportion of agricultural production area in a radius of 2000 m. Therefore, a drastic pesticide reduction in large buffers around nature conservation areas is necessary to avoid contamination of their insect fauna.
Smoking cessation reduces systemic inflammation and circulating endothelin-1
Authors: Derella Cassandra C. , Tingen Martha S. , Blanks Anson , Sojourner Samantha J. , Tucker Matthew A. , Thomas Jeffrey , Harris Ryan A.
Published: December 2021

Smoking increases systemic inflammation and circulating endothelin-1 (ET-1), both of which contribute to an elevated risk of cardiovascular disease (CVD). The present study sought to test the hypothesis that a 12-week smoking cessation intervention would contribute to a long-term reduction in circulating ET-1, tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6). 30 individuals participated in a 12-week evidence-based smoking cessation program at Augusta University. Serum cotinine, plasma inflammatory cytokines, and plasma ET-1 were determined at baseline, immediately after the 12-week cessation program (end of treatment, EOT), and 12-months (12M) following the cessation program. Serum cotinine was significantly reduced (p < 0.001) at EOT and 12M following the smoking cessation program. Compared to BL (7.0 ± 1.6 pg/mL), TNF-α was significantly reduced at EOT (6.3 ± 1.5 pg/mL, p = 0.001) and 12M (5.2 ± 2.7 pg/mL, p < 0.001). ET-1 was significantly lower at EOT (1.9 ± 0.6 pg/mL, p = 0.013) and at 12M (2.0 ± 0.8 pg/mL, p = 0.091) following smoking cessation compared with BL (2.3 ± 0.6 pg/mL). BL concentrations of cotinine were significantly associated with basal ET-1 (r = 0.449, p = 0.013) and the change in cotinine at 12M following smoking cessation was significantly associated with the change in plasma ET-1 at 12M (r = 0.457, p = 0.011). Findings from the present pilot investigation demonstrate that a 12-week smoking cessation program reduces circulating concentrations of ET-1 and TNF-α for at least a year. The reduction in serum cotinine was associated with the decrease in circulating ET-1. The attenuation in ET-1 and inflammation may in part, contribute to the lower risk of CVD that is observed with smoking cessation.
Detachable dissolvable microneedles: intra-epidermal and intradermal diffusion, effect on skin surface, and application in hyperpigmentation treatment
Authors: Sawutdeechaikul Pritsana , Kanokrungsee Silada , Sahaspot Thanyapat , Thadvibun Kamonwan , Banlunara Wijit , Limcharoen Benchaphorn , Sansureerungsikul Titiporn , Rutwaree Teeranut , Oungeun Miranda , Wanichwecharungruang Supason
Published: December 2021

Delivering bioactive compounds into skin tissue has long been a challenge. Using ex vivo porcine and rat skins, here we demonstrate that a detachable dissolvable microneedle (DDMN) array, a special dissolvable microneedle that allows needle detachment from the base within 2 min post administration, can effectively embed a model compound into epidermis and dermis. Diffusion of the compound from the needle embedding sites to the nearby skin tissue is demonstrated at various post administration periods. The relationship between the time that a conventional dissolvable microneedle array is left on skin without needle detachment from the base and the degree of skin surface abrasion at each microneedle penetration spot is also demonstrated on skin of human volunteers. Co-loading glutathione with vitamin C (vitC) can stabilize vitC in the DDMN. DDMN loaded with vitC and glutathione can help erasing post-acne-hyperpigmentation spots.
Role of eccentricity in early Holocene African and Asian summer monsoons
Authors: Wu Chi-Hua , Lee Shih-Yu , Tsai Pei-Chia
Published: December 2021

The effect of precession on paleoclimate changes depends on eccentricity. However, whether and to what degree eccentricity relates to millennial-scale monsoonal changes remain unclear. By investigating climate simulations with a fixed precession condition of 9 ka before the present, we explored the potential influence of eccentricity on early-Holocene changes in the Afro–Asian summer monsoons. Compared with the lower eccentricity of the present day, higher eccentricity in the early Holocene strengthened the continental summer monsoons, Pacific anticyclone, and Hadley circulation, particularly over the ocean. Over Africa, the eccentricity-induced “dry-gets-wetter” condition could be related to the Green Sahara, suggesting a superimposed effect of precession. Over the western Pacific, the tropical response to eccentricity may have been competitive in terms of what an extremely high obliquity may have caused. A downscaled modulation of eccentricity in relation to precession and obliquity cannot be ignored when paleomonsoon records are studied. Regarding early-Holocene monsoonal changes in South Asia, however, a high eccentricity may have had only a secondary effect on enhancing the monsoonal precipitation in the southern edge of the Tibetan Plateau, exhibiting the weak power of candle-like heating. This suggested that sizable monsoonal changes over the northern Indian Ocean and India–Pakistan region are unrelated to early-Holocene eccentricity.
Traits of a mussel transmissible cancer are reminiscent of a parasitic life style
Authors: Burioli E. A. V. , Hammel M. , Bierne N. , Thomas F. , Houssin M. , Destoumieux-Garzón D. , Charrière G. M.
Published: December 2021

Some cancers have evolved the ability to spread from host to host by transmission of cancerous cells. These rare biological entities can be considered parasites with a host-related genome. Still, we know little about their specific adaptation to a parasitic lifestyle. MtrBTN2 is one of the few lineages of transmissible cancers known in the animal kingdom. Reported worldwide, MtrBTN2 infects marine mussels. We isolated MtrBTN2 cells circulating in the hemolymph of cancerous mussels and investigated their phenotypic traits. We found that MtrBTN2 cells had remarkable survival capacities in seawater, much higher than normal hemocytes. With almost 100% cell survival over three days, they increase significantly their chances to infect neighboring hosts. MtrBTN2 also triggered an aggressive cancerous process: proliferation in mussels was ~ 17 times higher than normal hemocytes (mean doubling time of ~ 3 days), thereby favoring a rapid increase of intra-host population size. MtrBTN2 appears to induce host castration, thereby favoring resources re-allocation to the parasites and increasing the host carrying capacity. Altogether, our results highlight a series of traits of MtrBTN2 consistent with a marine parasitic lifestyle that may have contributed to the success of its persistence and dissemination in different mussel populations across the globe.
Synergistic interaction of renewable nipagin and eugenol for aromatic copoly(ether ester) materials with desired performance
Authors: Hu Keling , Sui Huachao , Zhao Dongping
Published: December 2021

Naturally occurring nipagin and eugenol were used as the collaborative starting materials for poly(ether ester) polymers. In this study, two series of nipagin and eugenol-derived copoly(ether ester)s, PHN11−xE1x and PHN11−xE2x (x = 0%, 5%, 10%, 15%, 20%), were prepared with renewable 1,6-hexanediol as a comonomer. The nipagin-derived component acts as the renewable surrogate of petroleum-based dimethyl terephthalate (DMT), while the eugenol-derived component acts as the cooperative property modifier of parent homopoly(ether ester) PHN1. 1,6-Hexanediol was chosen as the spacer because of its renewability, high boiling point, and short chain to enhance the glass transition temperatures (Tgs) of materials. The molecular weights and chemical structures were confirmed by gel permeation chromatograph (GPC), NMR and FTIR spectroscopies. Thermal and crystalline properties were studied by thermal gravimetric analysis (TGA), differential scanning calorimetric (DSC) and wide-angle X-ray diffraction (WXRD). The tensile assays were conducted to evaluate the mechanical properties. The results suggested that properties of this kind of poly(ether ester)s could be finely tuned by the relative content of two components for the desired applications (elastomer, rubbery) suitable for different scenarios from polyethylene glycol terephthalate (PET) and polybutylene terephthalate (PBT).
Connexin hemichannel inhibition ameliorates epidermal pathology in a mouse model of keratitis ichthyosis deafness syndrome
Authors: Sellitto Caterina , Li Leping , White Thomas W.
Published: December 2021

Mutations in five different genes encoding connexin channels cause eleven clinically defined human skin diseases. Keratitis ichthyosis deafness (KID) syndrome is caused by point mutations in the GJB2 gene encoding Connexin 26 (Cx26) which result in aberrant activation of connexin hemichannels. KID syndrome has no cure and is associated with bilateral hearing loss, blinding keratitis, palmoplantar keratoderma, ichthyosiform erythroderma and a high incidence of childhood mortality. Here, we have tested whether a topically applied hemichhanel inhibitor (flufenamic acid, FFA) could ameliorate the skin pathology associated with KID syndrome in a transgenic mouse model expressing the lethal Cx26-G45E mutation. We found that FFA blocked the hemichannel activity of Cx26-G45E in vitro, and substantially reduced epidermal pathology in vivo, compared to untreated, or vehicle treated control animals. FFA did not reduce the expression of mutant connexin hemichannel protein, and cessation of FFA treatment allowed disease progression to continue. These results suggested that aberrant hemichannel activity is a major driver of skin disease in KID syndrome, and that the inhibition of mutant hemichannel activity could provide an attractive target to develop novel therapeutic interventions to treat this incurable disease.