bluuebunny/crossref_metadata_2025 huggingface dataset:
Summary Judicial Proceedings as a Measure for Electoral Disinformation: Defining the European Standard
Authors: Krzywoń Adam
Published: June 2021

Electoral disinformation has become one of the most challenging problems for democratic states. All of them are facing the phenomenon of - both online and offline - dissemination of false information during pre-electoral period, which is harmful for individual and collective rights. As a consequence, some European countries adopted special measures, including summary judicial proceedings in order to declare that information or materials used in electioneering are false and to prohibit its further dissemination. There are already three rulings of the ECtHR concerning this expeditious judicial examination provided in the Polish law. In December 2018 France passed complex regulation against manipulation of information that include similar mechanisms. This article, basing on the ECtHR’s case law and some national experiences, attempts to define the minimal European standard for measures targeted at electoral disinformation, especially judicial summary proceeding. It contains the analysis of the notion of electoral disinformation, defines the state’s positive obligations in this sphere, and indicates mayor challenges for the legal framework. The principal argument is that summary judicial proceedings – if adequately designed – cannot be questioned from the Convention standpoint and provide a partial solution to the problem of electoral disinformation.
Diode-pumped 10 W femtosecond Yb:CALGO laser with high beam quality
Authors: Yang Jinfang , Wang Zhaohua , Song Jiajun , Lv Renchong , Wang Xianzhi , Zhu Jiangfeng , Wei Zhiyi
Published: June 2021

We demonstrate a diode-pumped femtosecond Yb:CaGdAlO4 (Yb:CALGO) laser with a semiconductor saturable absorber mirror (SESAM) for stable mode-locking operation. A perfect beam profile is measured under 10 W output power with

$M_{x}^{2}$

 = 1.017 and

$M_{y}^{2}$

 = 1.016 in the horizontal and vertical directions, respectively. At the repetition rate of 71.66 MHz, the optical pulse duration is 247 fs and the pulse energy is 140 nJ at the central wavelength of 1041 nm, corresponding to a peak power of 0.56 MW. In addition, we also generate continuous wave (CW) power of more than 15 W with TEM00 mode, corresponding to an optical-to-optical efficiency of 44.1%.
Deuterated polyethylene nanowire arrays for high-energy density physics
Authors: Capeluto M. G. , Curtis A. , Calvi C. , Hollinger R. , Shlyaptsev V. N. , Rocca J. J.
Published: June 2021

The interaction of intense, ultrashort laser pulses with ordered nanostructure arrays offers a path to the efficient creation of ultra-high-energy density (UHED) matter and the generation of high-energy particles with compact lasers. Irradiation of deuterated nanowires arrays results in a near-solid density environment with extremely high temperatures and large electromagnetic fields in which deuterons are accelerated to multi-megaelectronvolt energies, resulting in deuterium–deuterium (D–D) fusion. Here we focus on the method of fabrication and the characteristics of ordered arrays of deuterated polyethylene nanowires. The irradiation of these array targets with femtosecond pulses of relativistic intensity and joule-level energy creates a micro-scale fusion environment that produced

$2\times {10}^6$

 neutrons per joule, an increase of about 500 times with respect to flat solid CD2 targets irradiated with the same laser pulses. Irradiation with 8 J laser pulses was measured to generate up to 1.2 × 107 D–D fusion neutrons per shot.
Chronic Care Model in Italy: a narrative review of the literature
Authors: Petrelli Fabio , Cangelosi Giovanni , Nittari Giulio , Pantanetti Paola , Debernardi Giulia , Scuri Stefania , Sagaro Getu Gamo , Nguyen Cuc Thi Thu , Grappasonni Iolanda
Published: June 2021

Aim:

To analyze scientific literature on the development and implementation of the Chronic Care Model (CCM) in treating chronic diseases in the Italy context. Besides, to evaluate the effects of the activities carried out by the operators participating in the CCM on clinical care.

Background:

Italy is the second country globally for longevity, with 21.4% of citizens over 65 and 6.4% over 80. The CCM fits into this context, a care model aimed primarily at patients suffering from chronic diseases, especially in emergencies, as the recent COVID-19 pandemic.

Methods:

PubMed, Embase, Scopus, Cinahl, and Cochrane Library scientific databases were consulted, and the records selected as relevant by title and abstract by nine independent scholars, and disagreements were resolved through discussion. Finally, the studies included in this review were selected based on the eligibility criteria.

Results:

Twenty potentially relevant studies were selected, and after applying the eligibility criteria and screening by the Critical Appraisal Skills Program tool, eight included in this review. The studies showed the effectiveness of CCM for managing patients with heart failure in primary care settings and significant improvements in clinical outcomes, the reduction of inappropriate emergency room access for chronic patients, and the improvement of patients’ overall health with diabetes. The CCM organizational model is effective in improving the management of metabolic control and the main cardiovascular risk factors. Furthermore, this modality also allows doctors to dedicate more space to patients in the disease’s acute phase.

Conclusion:

The CCM, with its fundamental pillars of empowering self-management of care, could represent a valid alternative to health management. The managers of health services, especially territorial ones, could consider the CCM for the improvement of the treatments offered.
Hydrological Changes in Restricted Basins: Insights From Strontium Isotopes on Late Miocene‐Pliocene Connectivity of the Eastern Paratethys (Dacian Basin, Romania)
Authors: Vasiliev Iuliana , Stoica Marius , Grothe Arjen , Lazarev Sergei , Palcu Dan Valentin , van Baak Christiaan , De Leeuw Arjan , Sangiorgi Francesca , Reichart Gert‐Jan , Davies Gareth R. , Krijgsman Wout
Published: June 2021

The Dacian Basin was uniquely situated to record late Miocene hydrological changes that influenced depositional environments and faunal dispersal patterns in Central Eurasia's mega‐lake Paratethys. Differences between the high strontium isotope ratio (87Sr/86Sr) of the waters from Lake Pannon and local Carpathian rivers and low 87Sr/86Sr of the Eastern Paratethys (Black Sea ‒ Caspian Sea) allow a thorough investigation of connectivity and water fluxes in the transient Dacian Basin. We present a detailed 87Sr/86Sr record for the Dacian Basin, which provides an exceptional record of basin connectivity from the latest Tortonian (ca. 7.7 Ma) until the early Pleistocene (ca. 1.8 Ma). Data show that a late Tortonian transgression (7.6–7.4 Ma) started with an incursion of Eastern Paratethys waters into the Dacian Basin, after which local rivers became the dominant source for the mostly freshwater environments of the early Messinian. The regional Maeotian‐Pontian transitional interval (6.3–5.9 Ma) records a second incursion of Eastern Paratethys waters, but this time with an additional marine (Mediterranean) influx coinciding with a short‐lived salinity incursion. During the Messinian Salinity Crisis of the Mediterranean, the Dacian Basin progressively connected with the Eastern Paratethys (5.9–5.5 Ma), after which it became restricted during the peak Mediterranean lowstand (5.5 Ma) and filled with Lake Pannon and local river water (5.5–5.3 Ma). During the Plio‐Pleistocene, the Dacian Basin reconnected with the, at that time isolated, Black Sea, which shows similar 87Sr/86Sr as in the Last Glacial Maximum.
Twice‐Daily Monsoon Precipitation Maxima in the Himalayas Driven by Land Surface Effects
Authors: Fujinami Hatsuki , Fujita Koji , Takahashi Nobuhiro , Sato Tomonori , Kanamori Hironari , Sunako Sojiro , Kayastha Rijan B.
Published: June 2021

The diurnal cycle of precipitation is important to the hydroclimate in the Himalayas in summer; however, features of the diurnal cycle that affect precipitation from the foothills to glacierized, high‐elevation areas are poorly understood. We investigated the diurnal cycle of precipitation using 3 years of in situ observations recorded close to a glacier at 4,806 m asl, and 17 years of data from the Tropical Rainfall Measuring Mission (TRMM) precipitation radar (PR) and the Integrated Multi‐satellitE Retrieval for Global Precipitation Measurement (IMERG). The mechanisms that drive the diurnal cycle were examined using hourly European Center for Medium‐Range Weather Forecasts Re‐Analysis fifth generation (ERA5) data. In situ observations showed that the diurnal precipitation cycle has daytime and nighttime peaks, which both consist of high rainfall frequency and low rainfall intensity. In addition, twice‐daily maxima exist in the TRMM PR data, particularly over two rain bands at around 500–1,000 m asl, and at ∼2,000 m asl. Convective‐type rainfall, with a lower rain‐top height, occurs in the daytime, whereas stratiform‐type rain, with a higher rain‐top height, occurs at night, particularly over terrain at elevations above ∼1,500 m asl. Land surface processes likely cause the two peaks in the diurnal cycle. Daytime surface heating drives upslope flows that promote condensation. At night, surface cooling over the plain to the south of the Himalayas causes low‐level monsoon flows to accelerate, creating a nocturnal jet, which results in large‐scale moisture flux convergence over the southern slopes.
On the Ship Particle Number Emission Index: Size‐Resolved Microphysics and Key Controlling Parameters
Authors: Mao Jingbo , Zhang Yan , Yu Fangqun , Nair Arshad Arjunan , Yu Qi , Wang Lin , Ma Weichun , Chen Limin
Published: June 2021

Shipping particle number emission is important as it can influence cloud condensation nuclei abundance and thus indirectly affect clouds and perturb the Earth's radiation budget. Here, we integrate a size‐resolved Advanced Particle Microphysics module with a photochemical BOX MOdeling eXtension to the Kinetic PreProcessor and employ the resulting model to understand the microphysical and chemical characteristics of ship plumes. Simulated concentrations of key gaseous species and particle numbers are in good agreement compared with measurements from the NOAA Intercontinental Transport and Chemical Transformation (ITCT) 2K2 field study off the California coast. Further analysis reveals that significant new particle formation can occur in the plume and the growth of these secondary particles to 5–20 nm generally dominates the total particle numbers. We show that wind speed, emission rates of SO2 and NOx, solar irradiation, ambient temperature, and background [NH3] have strong nonlinear effects on the ship particle number emission index (EIPN). Depending on the ambient air and meteorological conditions, the model simulations show that EIPN can range from ∼2.5 × 1014 no. kg−1 fuel (dominated by primary particles) to ∼3.0 × 1018 no. kg−1 fuel (dominated by secondary particles). In consideration of the current worldwide expansion of Emission Control Areas, we systematically study how the EIPN decreases with reduction of fuel sulfur content to 0.1%. Our study highlights the necessity of accounting for the nonlinear dependence of secondary particle formation on key controlling parameters in calculating shipping particle number emissions, which is important for determining aerosol indirect climate effects.
Local Magnetic Activity Index Nowcast Based on Concurrent Measurements at Two Observatories in Close Proximity
Authors: Verhulst Tobias G. W. , Bracke Stephan , Humbled François , Stankov Stanimir M.
Published: June 2021

Permanent monitoring and real‐time indexing of the geomagnetic activity is of utmost importance for space weather services. In particular, providing a continuous and reliable local magnetic activity nowcast is of increasing importance as it can be used to generate alerts for various users, for instance for GNSS‐based applications or to protect electric power grids. This study presents a novel nowcast system for calculating a K‐type index of the local magnetic activity in Belgium. This includes a fully automated computer procedure for digital magnetogram data acquisition, data cleaning, calculating the index, displaying the results, and possibly issuing an alert to interested users, if the storm‐level activity is identified. Novel characteristics are the higher cadence of index calculation, an index reliability estimate based on data quality, and the high availability of the nowcast guaranteed by the operation of two identical instruments at observatories in close proximity. An evaluation of the index nowcast accuracy was carried out, and its results are also presented.
Improving Snow Estimates Through Assimilation of MODIS Fractional Snow Cover Data Using Machine Learning Algorithms and the Common Land Model
Authors: Hou Jinliang , Huang Chunlin , Chen Weijing , Zhang Ying
Published: June 2021

In this study, an innovative MODIS fractional snow cover (SCF) data assimilation (DA) prototype framework that invokes machine learning (ML) techniques and Common land model (CoLM) is proposed to improve the estimation of the snow depth (SD) and the SCF. To validate our new framework, we analyzed two snow seasons from 2013 to 2015 at 46 stations in Northern Xinjiang in China. We developed 12 SCF DA schemes that represent different DA methods (direct insertion (DI) and Ensemble Kalman Filter (EnKF)), observational data (original data and gap‐filled MODIS SCF data), and observation operators (five new snow depletion curves (SDCs) defined using traditional multivariate nonlinear regression and four ML methods). While improving the frequency of the SCF observations in the DI‐based DA scheme only resulted in a marginal improvement in the snow estimates, by adding new SDCs fitted by ML techniques (e.g., deep belief network), and the gap‐filled MODIS SCF data to the EnKF‐based DA scheme, we were able to reduce model structural uncertainties of CoLM and achieve marked improvement in the accuracy of the snow estimates (RMSE = 5.92 cm, mean bias error = −1.94 cm, and average degree of improvement = 32.18% for SD estimates and RMSE = 15. 79%, mean bias error = −1.21%, and average degree of improvement = 47.95% for SCF estimates). Our results demonstrate the feasibility of improving snow estimates by combining the ML techniques with physically based snowpack model in a SCF DA framework.
Salient Midlatitude Ionosphere‐Thermosphere Disturbances Associated With SAPS During a Minor but Geo‐Effective Storm at Deep Solar Minimum
Authors: Aa Ercha , Zhang Shun‐Rong , Erickson Philip J. , Coster Anthea J. , Goncharenko Larisa P. , Varney Roger H. , Eastes Richard
Published: June 2021

This work conducts a focused study of subauroral ion‐neutral coupling processes and midlatitude ionospheric/thermospheric responses in North America during a minor but quite geo‐effective storm on September 27–28, 2019 under deep solar minimum conditions. Several prominent storm‐time disturbances and associated electrodynamics/dynamics were identified and comprehensively analyzed using Millstone Hill and Poker Flat incoherent scatter radar measurements, Fabry‐Perot interferometer data, total electron content data from Global Navigation Satellite System observations, and thermospheric composition O/N2 data from the Global‐scale Observations of Limb and Disk mission. Despite solar minimum conditions, this minor storm produced several prominent dynamic features, in particular (a) Intense subauroral polarization stream (SAPS) of 1,000 m/s, overlapping with a deepened main trough structure. (b) An enhanced westward wind of 230 m/s and a significant poleward wind surge of 85 m/s occurred in the post‐SAPS period. (c) Large‐scale traveling ionospheric disturbances (TIDs) were generated and propagated equatorward across mid‐latitudes in the storm main phase. TID characteristics were significantly affected by SAPS, evolving into divergent propagation patterns. (d) SAPS was situated on the poleward edge of a considerable storm‐enhanced density structure. (e) The midlatitude ionosphere and thermosphere exhibited a prolonged positive storm effect in the main phase and beginning of recovery phase, with 5–10 TECU increase and 10%–30% O/N2 enhancement for 12 h. This was followed by a considerable negative storm effect with 5–10 TECU and 20%–40% O/N2 decrease. Results show that minor storm intervals can produce substantial mid‐latitude ionospheric and thermospheric dynamics in low solar flux conditions.
Herbal Products and Serious Side Effects: A Case of Ginseng‐Induced Manic Episode
Authors: Vázquez I. , Agüera‐Ortiz L. F.
Published: June 2021

Objective: Ginseng root extract is a widely used herbal product not devoid of side effects. This report describes the development of manic symptoms after ginseng consumption in a patient with affective disorder. Other potentially harmful side effects of ginseng are also reviewed.

Method: A single case report.

Results: A 56‐year‐old woman with previous affective disorder presented a manic episode during ginseng intake. Symptoms disappeared rapidly with low doses of neuroleptics and benzodiazepines after ginseng suppression.

Conclusion: Ginseng may produce manic symptoms. A special risk situation seems to be affective patients under antidepressant medication. The case emphasizes the lack of harmlessness of herbal products. Patients should be routinely asked about the use of herbal products and diet supplements.
A randomized phase 3 study of ixazomib–dexamethasone versus physician’s choice in relapsed or refractory AL amyloidosis
Authors: Dispenzieri Angela , Kastritis Efstathios , Wechalekar Ashutosh D. , Schönland Stefan O. , Kim Kihyun , Sanchorawala Vaishali , Landau Heather J. , Kwok Fiona , Suzuki Kenshi , Comenzo Raymond L. , Berg Deborah , Liu Guohui , Kumar Arun , Faller Douglas V. , Merlini Giampaolo
Published: June 2021

In the first phase 3 study in relapsed/refractory AL amyloidosis (TOURMALINE-AL1 NCT01659658), 168 patients with relapsed/refractory AL amyloidosis after 1–2 prior lines were randomized to ixazomib (4 mg, days 1, 8, 15) plus dexamethasone (20 mg, days 1, 8, 15, 22; n = 85) or physician’s choice (dexamethasone ± melphalan, cyclophosphamide, thalidomide, or lenalidomide; n = 83) in 28-day cycles until progression or toxicity. Primary endpoints were hematologic response rate and 2-year vital organ deterioration or mortality rate. Only the first primary endpoint was formally tested at this interim analysis. Best hematologic response rate was 53% with ixazomib–dexamethasone vs 51% with physician’s choice (p = 0.76). Complete response rate was 26 vs 18% (p = 0.22). Median time to vital organ deterioration or mortality was 34.8 vs 26.1 months (hazard ratio 0.53; 95% CI, 0.32–0.87; p = 0.01). Median treatment duration was 11.7 vs 5.0 months. Adverse events of clinical importance included diarrhea (34 vs 30%), rash (33 vs 20%), cardiac arrhythmias (26 vs 15%), nausea (24 vs 14%). Despite not meeting the first primary endpoint, all time-to-event data favored ixazomib–dexamethasone. These results are clinically relevant to this relapsed/refractory patient population with no approved treatment options.
Human milk feeding and cognitive outcome in preterm infants: the role of infection and NEC reduction
Authors: Lapidaire Winok , Lucas Alan , Clayden Jonathan D. , Clark Chris , Fewtrell Mary S.
Published: June 2021

Background

Breast milk has been associated with lower risk of infection and necrotising enterocolitis (NEC) and improved long-term cognitive outcomes in preterm infants but, if unsupplemented, does not meet the nutritional requirements of preterm infants.

Methods

Preterm infants were randomised to receive a high nutrient intervention diet: preterm formula (PTF) or the standard diet: term formula (TF) or banked donor breast milk (BBM), either as their sole diet or as supplement to maternal breast milk (MBM). IQ tests were performed at ages 7, 15, 20, and 30 years.

Results

An increase in MBM and BBM intake was associated with a lower chance of neonatal infection/NEC. Neonatal infection/NEC was associated with lower Full Scale IQ (FSIQ) and Performance IQ (PIQ) score at ages 7 and 30 years. The relationship between higher intake of MBM and PIQ at age 7 years was partly mediated by neonatal infection/NEC. The intervention diet was associated with higher Verbal IQ (VIQ) scores compared to the standard diet. There was no evidence that these effects changed from childhood through to adulthood.

Conclusions

Neonatal diet is an important modifiable factor that can affect long-term cognitive outcome through a ‘human milk’ factor, protecting against infection/NEC, and a ‘nutrient content’ factor.

Impact

This is the first study to demonstrate the effects of neonatal infection/necrotising enterocolitis (NEC) on IQ in the same cohort in childhood and adulthood.

Diet can be a key factor in long-term cognitive outcome in people born preterm by preventing neonatal infection/NEC and providing adequate nutrients.

Human milk, whether MBM or BBM, is associated with a reduced risk of infection/NEC.

A higher nutrient diet is associated with better cognitive outcome in childhood.

Performance IQ is particularly vulnerable to the effects of infection/NEC and verbal IQ to the quantity of (macro)nutrients in the diet.
Pathogenic variants in PIDD1 lead to an autosomal recessive neurodevelopmental disorder with pachygyria and psychiatric features
Authors: Zaki Maha S. , Accogli Andrea , Mirzaa Ghayda , Rahman Fatima , Mohammed Hiba , Porras-Hurtado Gloria Liliana , Efthymiou Stephanie , Maqbool Shazia , Shukla Anju , Vincent John B. , Hussain Abrar , Mir Asif , Beetz Christian , Leubauer Anika , Houlden Henry , Gleeson Joseph G. , Maroofian Reza
Published: June 2021

The PIDDosome is a multiprotein complex, composed by the p53-induced death domain protein 1 (PIDD1), the bipartite linker protein CRADD (also known as RAIDD) and the proform of caspase-2 that induces apoptosis in response to DNA damage. In the recent years, biallelic pathogenic variants in CRADD have been associated with a neurodevelopmental disorder (MRT34; MIM 614499) characterized by pachygyria with a predominant anterior gradient, megalencephaly, epilepsy and intellectual disability. More recently, biallelic pathogenic variants in PIDD1 have been described in a few families with apparently nonsydnromic intellectual disability. Here, we aim to delineate the genetic and radio-clinical features of PIDD1-related disorder. Exome sequencing was carried out in six consanguineous families. Thorough clinical and neuroradiological evaluation was performed for all the affected individuals as well as reviewing all the data from previously reported cases. We identified five distinct novel homozygous variants (c.2584C>T p.(Arg862Trp), c.1340G>A p.(Trp447*), c.2116_2120del p.(Val706Hisfs*30), c.1564_1565delCA p.(Gln522fs*44), and c.1804_1805del p.(Gly602fs*26) in eleven subjects displaying intellectual disability, behaviorial and psychiatric features, and a typical anterior-predominant pachygyria, remarkably resembling the CRADD-related neuroimaging pattern. In summary, we outlin`e the phenotypic and molecular spectrum of PIDD1 biallelic variants supporting the evidence that the PIDD1/CRADD/caspase-2 signaling is crucial for normal gyration of the developing human neocortex as well as cognition and behavior.
PEG-stabilized coaxial stacking of two-dimensional covalent organic frameworks for enhanced photocatalytic hydrogen evolution
Authors: Zhou Ting , Wang Lei , Huang Xingye , Unruangsri Junjuda , Zhang Hualei , Wang Rong , Song Qingliang , Yang Qingyuan , Li Weihua , Wang Changchun , Takahashi Kaito , Xu Hangxun , Guo Jia
Published: June 2021

Two-dimensional covalent organic frameworks (2D COFs) featuring periodic frameworks, extended π-conjugation and layered stacking structures, have emerged as a promising class of materials for photocatalytic hydrogen evolution. Nevertheless, the layer-by-layer assembly in 2D COFs is not stable during the photocatalytic cycling in water, causing disordered stacking and declined activity. Here, we report an innovative strategy to stabilize the ordered arrangement of layered structures in 2D COFs for hydrogen evolution. Polyethylene glycol is filled up in the mesopore channels of a β-ketoenamine-linked COF containing benzothiadiazole moiety. This unique feature suppresses the dislocation of neighbouring layers and retains the columnar π-orbital arrays to facilitate free charge transport. The hydrogen evolution rate is therefore remarkably promoted under visible irradiation compared with that of the pristine COF. This study provides a general post-functionalization strategy for 2D COFs to enhance photocatalytic performances.
Thbs1 induces lethal cardiac atrophy through PERK-ATF4 regulated autophagy
Authors: Vanhoutte Davy , Schips Tobias G. , Vo Alexander , Grimes Kelly M. , Baldwin Tanya A. , Brody Matthew J. , Accornero Federica , Sargent Michelle A. , Molkentin Jeffery D.
Published: June 2021

The thrombospondin (Thbs) family of secreted matricellular proteins are stress- and injury-induced mediators of cellular attachment dynamics and extracellular matrix protein production. Here we show that Thbs1, but not Thbs2, Thbs3 or Thbs4, induces lethal cardiac atrophy when overexpressed. Mechanistically, Thbs1 binds and activates the endoplasmic reticulum stress effector PERK, inducing its downstream transcription factor ATF4 and causing lethal autophagy-mediated cardiac atrophy. Antithetically, Thbs1−/− mice develop greater cardiac hypertrophy with pressure overload stimulation and show reduced fasting-induced atrophy. Deletion of Thbs1 effectors/receptors, including ATF6α, CD36 or CD47 does not diminish Thbs1-dependent cardiac atrophy. However, deletion of the gene encoding PERK in Thbs1 transgenic mice blunts the induction of ATF4 and autophagy, and largely corrects the lethal cardiac atrophy. Finally, overexpression of PERK or ATF4 using AAV9 gene-transfer similarly promotes cardiac atrophy and lethality. Hence, we identified Thbs1-mediated PERK-eIF2α-ATF4-induced autophagy as a critical regulator of cardiomyocyte size in the stressed heart.
The human nucleoporin Tpr protects cells from RNA-mediated replication stress
Authors: Kosar Martin , Giannattasio Michele , Piccini Daniele , Maya-Mendoza Apolinar , García-Benítez Francisco , Bartkova Jirina , Barroso Sonia I. , Gaillard Hélène , Martini Emanuele , Restuccia Umberto , Ramirez-Otero Miguel Angel , Garre Massimiliano , Verga Eleonora , Andújar-Sánchez Miguel , Maynard Scott , Hodny Zdenek , Costanzo Vincenzo , Kumar Amit , Bachi Angela , Aguilera Andrés , Bartek Jiri , Foiani Marco
Published: June 2021

Although human nucleoporin Tpr is frequently deregulated in cancer, its roles are poorly understood. Here we show that Tpr depletion generates transcription-dependent replication stress, DNA breaks, and genomic instability. DNA fiber assays and electron microscopy visualization of replication intermediates show that Tpr deficient cells exhibit slow and asymmetric replication forks under replication stress. Tpr deficiency evokes enhanced levels of DNA-RNA hybrids. Additionally, complementary proteomic strategies identify a network of Tpr-interacting proteins mediating RNA processing, such as MATR3 and SUGP2, and functional experiments confirm that their depletion trigger cellular phenotypes shared with Tpr deficiency. Mechanistic studies reveal the interplay of Tpr with GANP, a component of the TREX-2 complex. The Tpr-GANP interaction is supported by their shared protein level alterations in a cohort of ovarian carcinomas. Our results reveal links between nucleoporins, DNA transcription and replication, and the existence of a network physically connecting replication forks with transcription, splicing, and mRNA export machinery.
Nuclear ADP-ribosylation drives IFNγ-dependent STAT1α enhancer formation in macrophages
Authors: Gupte Rebecca , Nandu Tulip , Kraus W. Lee
Published: June 2021

STAT1α is a key transcription factor driving pro-inflammatory responses in macrophages. We found that the interferon gamma (IFNγ)-regulated transcriptional program in macrophages is controlled by ADP-ribosylation (ADPRylation) of STAT1α, a post-translational modification resulting in the site-specific covalent attachment of ADP-ribose moieties. PARP-1, the major nuclear poly(ADP-ribose) polymerase (PARP), supports IFNγ-stimulated enhancer formation by regulating the genome-wide binding and IFNγ-dependent transcriptional activation of STAT1α. It does so by ADPRylating STAT1α on specific residues in its DNA-binding domain (DBD) and transcription activation (TA) domain. ADPRylation of the DBD controls STAT1α binding to its cognate DNA elements, whereas ADPRylation of the TA domain regulates enhancer activation by modulating STAT1α phosphorylation and p300 acetyltransferase activity. Loss of ADPRylation at either site leads to diminished IFNγ-dependent transcription and downstream pro-inflammatory responses. We conclude that PARP-1-mediated ADPRylation of STAT1α drives distinct enhancer activation mechanisms and is a critical regulator of inflammatory responses in macrophages.
Diversity-oriented synthesis of nanographenes enabled by dearomative annulative π-extension
Authors: Matsuoka Wataru , Ito Hideto , Sarlah David , Itami Kenichiro
Published: June 2021

Nanographenes and polycyclic aromatic hydrocarbons (PAHs) are among the most important classes of compounds, with potential applications in nearly all areas of science and technology. While the theoretically possible number of nanographene structures is extraordinary, most of these molecules remain synthetically out of reach due to a lack of programmable and diversity-oriented synthetic methods, and their potentially huge structure-property diversity has not been fully exploited. Herein we report a diversity-oriented, growth-from-template synthesis of nanographenes enabled by iterative annulative π-extension (APEX) reactions from small PAH starting materials. The developed dearomative annulative π-extension (DAPEX) reaction enables π-elongation at the less-reactive M-regions of PAHs, and is successfully combined with complementary APEX reactions that occur at K- and bay-regions to access a variety of previously untapped nanographenes.
Damage mechanism identification in composites via machine learning and acoustic emission
Authors: Muir C. , Swaminathan B. , Almansour A. S. , Sevener K. , Smith C. , Presby M. , Kiser J. D. , Pollock T. M. , Daly S.
Published: June 2021

Damage mechanism identification has scientific and practical ramifications for the structural health monitoring, design, and application of composite systems. Recent advances in machine learning uncover pathways to identify the waveform-damage mechanism relationship in higher-dimensional spaces for a comprehensive understanding of damage evolution. This review evaluates the state of the field, beginning with a physics-based understanding of acoustic emission waveform feature extraction, followed by a detailed overview of waveform clustering, labeling, and error analysis strategies. Fundamental requirements for damage mechanism identification in any machine learning framework, including those currently in use, under development, and yet to be explored, are discussed.
Adaptive quantum state tomography with neural networks
Authors: Quek Yihui , Fort Stanislav , Ng Hui Khoon
Published: June 2021

Current algorithms for quantum state tomography (QST) are costly both on the experimental front, requiring measurement of many copies of the state, and on the classical computational front, needing a long time to analyze the gathered data. Here, we introduce neural adaptive quantum state tomography (NAQT), a fast, flexible machine-learning-based algorithm for QST that adapts measurements and provides orders of magnitude faster processing while retaining state-of-the-art reconstruction accuracy. As in other adaptive QST schemes, measurement adaptation makes use of the information gathered from previous measured copies of the state to perform a targeted sensing of the next copy, maximizing the information gathered from that next copy. Our NAQT approach allows for a rapid and seamless integration of measurement adaptation and statistical inference, using a neural-network replacement of the standard Bayes’ update, to obtain the best estimate of the state. Our algorithm, which falls into the machine learning subfield of “meta-learning” (in effect “learning to learn” about quantum states), does not require any ansatz about the form of the state to be estimated. Despite this generality, it can be retrained within hours on a single laptop for a two-qubit situation, which suggests a feasible time-cost when extended to larger systems and potential speed-ups if provided with additional structure, such as a state ansatz.
Guiding urban water management towards 1.5 °C
Authors: Parkinson Simon
Published: June 2021

Reliable access to clean and affordable water is prerequisite for human well being, but its provision in cities generates environmental externalities including greenhouse gas (GHG) emissions. As policy-makers target opportunities to mitigate GHGs in line with the Paris Agreement, it remains vague how urban water management can contribute to the goal of limiting climate warming to 1.5 °C. This perspective guides policy-makers in the selection of innovative technologies and strategies for leveraging urban water management as a climate change mitigation solution. Recent literature, data and scenarios are reviewed to shine a light on the GHG mitigation potential and the key areas requiring future research. Increasing urban water demands in emerging economies and over-consumption in developed regions pose mitigation challenges due to energy and material requirements that can be partly offset through end-use water conservation and expansion of decentralized, nature-based solutions. Policies that integrate urban water and energy flows, or reconfigure urban water allocation at the river basin-level remain untapped mitigation solutions with large gaps in our understanding of potentials.
Study on the average speed of particles from a particle swarm derived from a stationary particle swarm
Authors: Guo Tao
Published: June 2021

It has been more than 100 years since the advent of special relativity, but the reasons behind the related phenomena are still unknown. This article aims to inspire people to think about such problems. With the help of Mathematica software, I have proven the following problem by means of statistics: In 3-dimensional Euclidean space, for point particles whose speeds are c and whose directions are uniformly distributed in space (assuming these particles’ reference system is $$\mathcal {R}_{0}$$

R
0

, if their average velocity is 0), when some particles (assuming their reference system is $$\mathcal {R}_{u}$$

R
u

), as a particle swarm, move in a certain direction with a group speed u (i.e., the norm of the average velocity) relative to $$\mathcal {R}_{0}$$

R
0

, their (or the sub-particle swarm’s) average speed relative to $$\mathcal {R}_{u}$$

R
u

is slower than that of particles (or the same scale sub-particle swarm) in $$\mathcal {R}_{0}$$

R
0

relative to $$\mathcal {R}_{0}$$

R
0

. The degree of slowing depends on the speed u of $$\mathcal {R}_{u}$$

R
u

and accords with the quantitative relationship described by the Lorentz factor $$\frac{c}{\sqrt{c^2-u^2}}$$

c

c
2

-

u
2

. Base on this conclusion, I have deduced the speed distribution of particles in $$\mathcal {R}_{u}$$

R
u

when observing from $$\mathcal {R}_{0}$$

R
0

.
Chimeric vaccine designs against Acinetobacter baumannii using pan genome and reverse vaccinology approaches
Authors: Shahid Fatima , Zaheer Tahreem , Ashraf Shifa Tariq , Shehroz Muhammad , Anwer Farha , Naz Anam , Ali Amjad
Published: June 2021

Acinetobacter baumannii (A. baumannii), an opportunistic, gram-negative pathogen, has evoked the interest of the medical community throughout the world because of its ability to cause nosocomial infections, majorly infecting those in intensive care units. It has also drawn the attention of researchers due to its evolving immune evasion strategies and increased drug resistance. The emergence of multi-drug-resistant-strains has urged the need to explore novel therapeutic options as an alternative to antibiotics. Due to the upsurge in antibiotic resistance mechanisms exhibited by A. baumannii, the current therapeutic strategies are rendered less effective. The aim of this study is to explore novel therapeutic alternatives against A. baumannii to control the ailed infection. In this study, a computational framework is employed involving, pan genomics, subtractive proteomics and reverse vaccinology strategies to identify core promiscuous vaccine candidates. Two chimeric vaccine constructs having B-cell derived T-cell epitopes from prioritized vaccine candidates; APN, AdeK and AdeI have been designed and checked for their possible interactions with host BCR, TLRs and HLA Class I and II Superfamily alleles. These vaccine candidates can be experimentally validated and thus contribute to vaccine development against A. baumannii infections.
Atmospheric reaction of hydrazine plus hydroxyl radical
Authors: Douroudgari Hamed , Vahedpour Morteza , Khouini Fahime
Published: June 2021

Understanding the mechanism of hydrazine oxidation reaction by OH radical along with the rate constants of all possible pathways leads to explain the fate of hydrazine in the atmosphere. In this article, the comprehensive mechanisms and kinetics of the hydrazine plus hydroxyl radical reaction have been investigated theoretically at different temperatures and pressures. To achieve the main goals, a series of high levels of quantum chemical calculations have been widely implemented in reliable channels of the H-abstraction, SN2, and addition/elimination reactions. The energy profile of all pathways accompanied by the molecular properties of the involved stationary points has been characterized at the MP2, M06-2X, and CCSD(T)/CBS levels. To estimate accurate barrier energies of the H-abstraction channels, large numbers of the CCSD (T) calculations in conjunction with various augmented basis sets have been implemented. The direct dynamic calculations have been carried out using the validated M06-2X/maug-cc-pVTZ level, and also by the CCSD(T) (energies) + MP2 (partition functions) level. The pressure-dependent rate constants of the barrierless pathways have been investigated by the strong collision approach. Therefore, the main behaviors of the N2H4 + OH reaction have been explored according to the influences of temperature and pressure on the computed rate coefficients within the well-behaved theoretical frameworks of the TST, VTST, and RRKM theories. It has been found that the H-abstraction mechanism (to form N2H3) is dominant relative to the SN2 reaction and OH-addition to the N center of N2H4moiety (to form H2NOH + NH2). The computed high pressure limit rate constant of the main reaction pathway, k(298.15) = 7.31 × 10–11 cm3molecule−1 s−1, has an excellent agreement with the experimental value (k (298.15) = (6.50 ± 1.3) × 10–11 cm3molecule−1 s−1) recommended by Vaghjiani. Also, the atmospheric lifetime of hydrazine degradation by OH radicals has been demonstrated to be 32.80 to 1161.11 h at the altitudes of 0–50 km. Finally, the disagreement in the calculated rate constants between the previous theoretical study and experimental results has been rectified.
Desmoglein-2 harnesses a PDZ-GEF2/Rap1 signaling axis to control cell spreading and focal adhesions independent of cell–cell adhesion
Authors: Shelton W. Tucker , Thomas S. Madison , Alexander Hunter R. , Thomes C. Evan , Conway Daniel E. , Dubash Adi D.
Published: June 2021

Desmosomes have a central role in mediating extracellular adhesion between cells, but they also coordinate other biological processes such as proliferation, differentiation, apoptosis and migration. In particular, several lines of evidence have implicated desmosomal proteins in regulating the actin cytoskeleton and attachment to the extracellular matrix, indicating signaling crosstalk between cell–cell junctions and cell–matrix adhesions. In our study, we found that cells lacking the desmosomal cadherin Desmoglein-2 (Dsg2) displayed a significant increase in spreading area on both fibronectin and collagen, compared to control A431 cells. Intriguingly, this effect was observed in single spreading cells, indicating that Dsg2 can exert its effects on cell spreading independent of cell–cell adhesion. We hypothesized that Dsg2 may mediate cell–matrix adhesion via control of Rap1 GTPase, which is well known as a central regulator of cell spreading dynamics. We show that Rap1 activity is elevated in Dsg2 knockout cells, and that Dsg2 harnesses Rap1 and downstream TGFβ signaling to influence both cell spreading and focal adhesion protein phosphorylation. Further analysis implicated the Rap GEF PDZ-GEF2 in mediating Dsg2-dependent cell spreading. These data have identified a novel role for Dsg2 in controlling cell spreading, providing insight into the mechanisms via which cadherins exert non-canonical junction-independent effects.
Exoproteomic analysis of two MLST clade 2 strains of Clostridioides difficile from Latin America reveal close similarities
Authors: de Melo Pacífico Dvison , Costa Cecília Leite , Moura Hercules , Barr John R. , Maia Guilherme Augusto , Filho Vilmar Benetti , Moreira Renato Simões , Wagner Glauber , Domingues Regina Maria Cavalcanti Pilotto , Quesada-Gómez Carlos , de Oliveira Ferreira Eliane , de Castro Brito Gerly Anne
Published: June 2021

Clostridioides difficile BI/NAP1/ribotype 027 is an epidemic hypervirulent strain found worldwide, including in Latin America. We examined the genomes and exoproteomes of two multilocus sequence type (MLST) clade 2 C. difficile strains considered hypervirulent: ICC-45 (ribotype SLO231/UK[CE]821), isolated in Brazil, and NAP1/027/ST01 (LIBA5756), isolated during a 2010 outbreak in Costa Rica. C. difficile isolates were cultured and extracellular proteins were analyzed using high-performance liquid chromatography-tandem mass spectrometry. Genomic analysis revealed that these isolates shared most of the gene composition. Only 83 and 290 NAP1/027 genes were considered singletons in ICC-45 and NAP1/027, respectively. Exoproteome analysis revealed 197 proteins, of which 192 were similar in both strains. Only five proteins were exclusive to the ICC-45 strain. These proteins were involved with catalytic and binding functions and indirectly interacted with proteins related to pathogenicity. Most proteins, including TcdA, TcdB, flagellin subunit, and cell surface protein, were overrepresented in the ICC-45 strain; 14 proteins, including mature S-layer protein, were present in higher proportions in LIBA5756. Data are available via ProteomeXchange with identifier PXD026218. These data show close similarity between the genome and proteins in the supernatant of two strains with hypervirulent features isolated in Latin America and underscore the importance of epidemiological surveillance of the transmission and emergence of new strains.
A link between pH homeostasis and colistin resistance in bacteria
Authors: Panta Pradip R. , Doerrler William T.
Published: June 2021

Colistin resistance is complex and multifactorial. DbcA is an inner membrane protein belonging to the DedA superfamily required for maintaining extreme colistin resistance of Burkholderia thailandensis. The molecular mechanisms behind this remain unclear. Here, we report that ∆dbcA displays alkaline pH/bicarbonate sensitivity and propose a role of DbcA in extreme colistin resistance of B. thailandensis by maintaining cytoplasmic pH homeostasis. We found that alkaline pH or presence of sodium bicarbonate displays a synergistic effect with colistin against not only extremely colistin resistant species like B. thailandensis and Serratia marcescens, but also a majority of Gram-negative and Gram-positive bacteria tested, suggesting a link between cytoplasmic pH homeostasis and colistin resistance across species. We found that lowering the level of oxygen in the growth media or supplementation of fermentable sugars such as glucose not only alleviated alkaline pH stress, but also increased colistin resistance in most bacteria tested, likely by avoiding cytoplasmic alkalinization. Our observations suggest a previously unreported link between pH, oxygen, and colistin resistance. We propose that maintaining optimal cytoplasmic pH is required for colistin resistance in a majority of bacterial species, consistent with the emerging link between cytoplasmic pH homeostasis and antibiotic resistance.
Considerations for quality assurance of multiplex malaria antigen detection assays with large sample sets
Authors: Alvarado Rachel , van den Hoogen Lotus L. , Iriemenam Nnaemeka C. , Akinmulero Oluwaseun O. , Thomas Andrew N. , Tamunonengiyeofori Israel , Erasogie Evbuomwan , Chimaoge Achugbu C. , Dawurung Ayuba B. , Esiekpe Mudiaga K. , Okoli Mary U. , Mba Nwando , Ogunniyi Abiodun , Abimiku Alash’le , Maire Mark , Bassey Orji O. , Okoye McPaul , Swaminathan Mahesh , Greby Stacie M. , Ndodo Nnaemeka , Ihekweazu Chikwe , Abubakar Ado , Steinhardt Laura , Rogier Eric
Published: June 2021

Multiplex assays for malaria antigen detection can gather data from large sample sets, but considerations for the consistency and quality assurance (QA) of mass testing lack evaluation. We present a QA framework for a study occurring November 2019 to March 2020 involving 504 assay plates detecting four Plasmodium antigens: pan-Plasmodium aldolase and lactate dehydrogenase (LDH), histidine-rich protein 2 (HRP2), P. vivax LDH (PvLDH). Controls on each plate included buffer blank, antigen negative blood, and 4-point positive dilution curve. The blank and negative blood provided consistently low signal for all targets except for pAldolase, which showed variability. Positive curve signals decreased throughout the 5-month study duration but retained a coefficient of variation (CV) of < 5%, with the exception of HRP2 in month 5 (CV of 11%). Regression fittings for inter-plate control signals provided mean and standard deviations (SDs), and of 504 assay plates, 6 (1.2%) violated the acceptable deviation limits and were repeated. For the 40,272 human blood samples assayed in this study, of 161,088 potential data points (each sample × 4 antigens), 160,641 (99.7%) successfully passed quality checks. The QA framework presented here can be utilized to ensure quality of laboratory antigen detection for large sample sets.
Relationship between intraventricular hemorrhage and acute kidney injury in premature infants and its effect on neonatal mortality
Authors: Al-Mouqdad Mountasser M. , Huseynova Roya , Khalil Thanaa M. , Asfour Yasmeen S. , Asfour Suzan S.
Published: June 2021

Intraventricular hemorrhage (IVH) and acute kidney injury (AKI) are important neonatal morbidities in premature infants. This study aimed to investigate the relationship between IVH and AKI in premature infants and whether this association affects the incidence of neonatal mortality. Infants [gestational age (GA) ≤ 32 weeks; birth weight (BW) < 1500 g] were retrospectively evaluated in a large tertiary neonatal intensive care unit. Of 710 premature infants, 268 (37.7%) developed AKI. Infants with IVH were more likely to have AKI than those without IVH. Infants with severe IVH had a higher incidence of AKI than infants with mild IVH. Infants younger than 28 weeks with IVH were more likely to have AKI than those without IVH. An association between IVH grades and AKI stages was observed in the overall study population, in infants with GA < 28 weeks, and in infants with GA between 28 and 32 weeks. Mortality was increased 1.5 times in infants with IVH and AKI compared with that in infants with IVH but without AKI. Furthermore, mortality was increased in infants with IVH and AKI compared with infants without IVH or AKI. This study shows a direct relationship between the severity of IVH and the degree of AKI; both IVH and AKI increase the incidence of neonatal mortality.