bluuebunny/crossref_metadata_2025 huggingface dataset:
Mechanical Stress Effects on 550 °C Hot Corrosion Propagation Rates in Precipitation Hardened Ni-Base Superalloys: CMSX-4, CM247LC DS and IN6203DS
Authors: Chapman Neil , Gray Simon , Sumner Joy , Nicholls John
Published: December 2021

Combinations of temperature, stress and hot corrosion may cause environmentally-assisted cracking in precipitation-hardened Ni-base superalloys, which is little understood. This research aims to increase current understanding by investigating the effects of mechanical stress on the hot corrosion propagation rate during corrosion-fatigue testing of CMSX-4, CM247LC DS and IN6203DS. The parameters used during the tests included a high R-ratio, high frequency, and a temperature of 550 °C. The results showed CMSX-4 experienced a predictable increase in the hot corrosion rate, CM247LC DS also experienced increased rates, but no obvious trend was apparent; whilst IN6203DS showed no evidence of an increased rate. These different behaviours appear to be a result of an interaction between the mechanical stress and microstructural features, which include gamma-prime volume fractions in both the matrix and eutectic regions, along with the distribution of the eutectic structure. The different behaviours in the hot corrosion propagation rate subsequently affected the respective corrosion fatigue results, with both CMSX-4 and CM247LC DS experiencing fracture but with significantly more scatter involved in the CM247LC DS results. All IN6203DS corrosion-fatigue specimens completed the respective tests without fracture and showed no evidence of cracking. It, therefore, appears that precipitation hardened Ni-base superalloys, which are susceptible to environmentally-assisted cracking, also experience increased hot corrosion propagation rates.
Clean Electricity, Dirty Electricity: The Effect on Local House Prices
Authors: Eichholtz Piet , Kok Nils , Langen Mike , van Vulpen Daan
Published: December 2021

Renewable energy production is one of the most important policy instruments to fight climate change. However, despite global benefits, renewable energy production entails some local challenges, such as requiring more space per unit production capacity. In this paper, we study the external effects of large-scale conventional and renewable electric power generation facilities on local house prices. We combine information of all coal, gas, and biomass plants, as well as all wind turbines in the Netherlands, with 1.5 million housing transactions over a period of 30 years. Using a difference-in-difference as well as a repeated sales model, we study the effects of facility openings and closings. Our results show negative external price effects for gas plants and wind turbines, but positive effects for biomass plants, conditionally upon ex-ante lower priced locations. The external effects of power generating facilities on local housing markets are important to consider, especially with the current focus of public policies on the expansion of renewable energy generation. Our paper is one of the first to present a large-scale study, using detailed information, and comparing several different energy sources in one framework.
Comparison of Five Near-Infrared Fluorescent Folate Conjugates in an Ovarian Cancer Model
Authors: García de Jalón Elvira , Kleinmanns Katrin , Fosse Vibeke , Davidson Ben , Bjørge Line , Haug Bengt Erik , McCormack Emmet
Published: December 2021

Purpose

Fluorescence imaging (FLI) using targeted near-infrared (NIR) conjugates aids the detection of tumour lesions pre- and intraoperatively. The optimisation of tumour visualisation and contrast is essential and can be achieved through high tumour-specificity and low background signal. However, the choice of fluorophore is recognised to alter biodistribution and clearance of conjugates and is therefore a determining factor in the specificity of target binding. Although ZW800-1, IRDye® 800CW and ICG are the most commonly employed NIR fluorophores in clinical settings, the fluorophore with optimal in vivo characteristics has yet to be determined. Therefore, we aimed to characterise the impact the choice of fluorophore has on the biodistribution, specificity and contrast, by comparing five different NIR fluorophores conjugated to folate, in an ovarian cancer model.

Procedures

ZW800-1, ZW800-1 Forte, IRDye® 800CW, ICG-OSu and an in-house synthesised Cy7 derivative were conjugated to folate through an ethylenediamine linker resulting in conjugates 1–5, respectively. The optical properties of all conjugates were determined by spectroscopy, the specificity was assessed in vitro by flow cytometry and FLI, and the biodistribution was studied in vivo and ex vivo in a subcutaneous Skov-3 ovarian cancer model.

Results

We demonstrated time- and receptor-dependent binding of folate conjugates in vitro and in vivo. Healthy tissue clearance characteristics and tumour-specific signal varied between conjugates 1–5. ZW800-1 Forte (2) revealed the highest contrast in folate receptor alpha (FRα)-positive xenografts and showed statistically significant target specificity. While conjugates 1, 2 and 3 are renally cleared, hepatobiliary excretion and no or very low accumulation in tumours was observed for 4 and 5.

Conclusions

The choice of fluorophore has a significant impact on the biodistribution and tumour contrast. ZW800-1 Forte (2) exhibited the best properties of those tested, with significant specific fluorescence signal.
Der Biomarker Lipoprotein(a) – Lp(a) in der Diagnostik der peripheren arteriellen Verschlusskrankheit
Authors: Oremek G. M. , Passek K. , Dröge J. , Holzgreve F. , Ohlendorf D.
Published: December 2021

Die vorliegende Übersicht zum Biomarker „Lipoprotein(a) – Lp(a)“ wird im Rahmen der Serie Diagnostika des Zentralblatts für Arbeitsmedizin, Arbeitsschutz und Ergonomie publiziert, die sich mit dem immer häufigeren Gebrauch der Bestimmung von spezifischen Markern bei sog. Manager-Vorsorgen und Check-up-Untersuchungen beschäftigt. Lipoprotein(a), Lp(a), eignet sich grundsätzlich nicht für solche Vorsorgen, sondern ist ein Marker zur Risikoabschätzung der peripheren arteriellen Verschlusskrankheit. Hier zeigt dieser eine hohe Sensitivität und Spezifität, wobei der Marker aber auf keinen Fall als Screeningparameter zur Frühdiagnostik eingesetzt werden sollte.
Using a pre-kicker to ensure safe extractions from the HEPS storage ring
Authors: Duan Zhe , Chen Jin-Hui , Shi Hua , Tang Guang-Yi , Wang Lei , Wu Yu-Wen
Published: December 2021

The High Energy Photon Source (HEPS) is a 6 GeV diffraction-limited storage ring light source under construction. The swap-out injection is adopted with the depleted bunch recycled via high-energy accumulation in the booster. The extremely high beam energy density of the bunches with an ultra-low emittance (about 30 pm horizontally and 3 pm vertically) and high bunch charges (from 1.33 to 14.4 nC) extracted from the storage ring could cause hazardous damage to the extraction Lambertson magnet in case of extraction kicker failure. To this end, we proposed the use of a pre-kicker to spoil the bunches prior to extraction, significantly reducing the maximum beam energy density down to within a safe region while still maintaining highly efficient extractions. The main parameters of the pre-kicker are simulated and discussed.
Rights of Families of Disappeared Persons
Authors: Baranowska Grażyna
Published: December 2021

This book examines how international judicial and non-judicial bodies in Europe address the needs of the families of forcibly disappeared persons. The needs in question are returning the remains of disappeared persons; the right to truth; the acceptance of responsibility by states; and the right to compensation. These have been identified as the four most commonly shared basic and fundamental needs of families in which an adult was disappeared many years previously and is now assumed to be dead, which is representative of the situation of the vast majority of families of disappeared persons in Europe.

The analysis covers the judgments and decisions of the European Court of Human Rights, the UN Human Rights Committee, the International Criminal Tribunal for the former Yugoslavia, the Human Rights Chamber for Bosnia and Herzegovina, and the Human Rights Advisory Panel in Kosovo, as well as the activities of the Committee on Missing Persons in Cyprus, the Special Process on Missing Persons in the Territory of former Yugoslavia, the UN Committee on Enforced Disappearances and the International Commission on Missing Persons. In so doing, the book demonstrates whether, how, and based on what principles these four needs of the families of disappeared persons can constitute a claim based on international human rights law.
Influence of sucrose reduction on fouling during the production of dulce de leche
Authors: Mauricio Erica F. , Francisquini Júlia D. A. , de Paula Igor L. , de Cezarino Junior José C. C. , de Oliveira Luiz F. C. , Stephani Rodrigo , De Carvalho Antônio F. , Perrone Ítalo T.
Published: December 2021

In this Research Communication we focus the food industry´s broad tendency to decrease sugar content in food products onto dulce de leche (DL) and examine the influence of sucrose reduction on the detrimental deposits formed during the production process. The method used to identify the impact produced directly on the heat exchanger during the production of this product with low sucrose content required varying the quantity of sucrose in the milk. Different percentages of sucrose (20, 15, 10, 5 and 0% w/w) were submitted to the DL concentration process in a process simulator. After concentration, the quantification of the deposits formed in each was carried out and these deposits were characterized according to their composition. Methods such as Kjeldahl, Pregl-Dumas and sem-EDS were used. Thus, the work highlights the need to change the product manufacturing process due to changes in the formulation that directly impact the formation of deposits in the equipment used (fouling). This deposit changes significantly in relation to its quantity as well as in relation to the composition and chemical characteristics as the gradual reduction of the sucrose content in the production takes place. Therefore, these impacts must be considered in order to maintain better manufacturing and ensure efficient cleaning of equipment.
A customised laryngeal stent for glottic airway reconstruction
Authors: Joshi A A , Agrawal S R , Bradoo R A
Published: December 2021

Objective

Laryngotracheal reconstructive surgery very often requires placement of laryngeal stents, but most of the available stents either do not conform to the shape of the glottis or are open at the upper end, causing significant tissue reaction and aspiration. LT-Mold is an ideal stent in this respect, but it is not readily available.

Case report

The authors of this study fashioned a laryngeal stent out of a readily available Montgomery T-tube in such a way that it had a closed upper end and was well-conformed to the architecture of the larynx. This stent was used in a case of posterior expansion laryngoplasty, and post-operatively the patient had a patent airway with good voice and no aspiration.

Conclusion

A customised laryngeal stent is well tolerated and helps to solve complicated cases of posterior glottic stenosis.
Test particle acceleration in resistive torsional fan magnetic reconnection using laboratory plasma parameters
Authors: Chesny D.L. , Orange N.B. , Hatfield K.W.
Published: December 2021

Particle acceleration via magnetic reconnection is a fundamental process in astrophysical plasmas. Experimental architectures are able to confirm a wide variety of particle dynamics following the two-dimensional Sweet–Parker model, but are limited in their reproduction of the fan-spine magnetic field topology about three-dimensional (3-D) null points. Specifically, there is not yet an experiment featuring driven 3-D torsional magnetic reconnection. To move in this direction, this paper expands on recent work toward the design of an experimental infrastructure for inducing 3-D torsional fan reconnection by predicting feasible particle acceleration profiles. Solutions to the steady-state, kinematic, resistive magnetohydrodynamic equations are used to numerically calculate particle trajectories from a localized resistivity profile using well-understood laboratory plasma parameters. We confine a thin, 10 eV helium sheath following the snowplough model into the region of this localized resistivity and find that it is accelerated to energies of

${\approx }2$

keV. This sheath is rapidly accelerated and focused along the spine axis propagating a few centimetres from the reconnection region. These dynamics suggest a novel architecture that may hold promise for future experiments studying solar coronal particle acceleration and for technology applications such as spacecraft propulsion.
Confluence of algebraic rewriting systems
Authors: Chenavier Cyrille , Dupont Benjamin , Malbos Philippe
Published: December 2021

Convergent rewriting systems on algebraic structures give methods to solve decision problems, to prove coherence results, and to compute homological invariants. These methods are based on higher-dimensional extensions of the critical branching lemma that proves local confluence from confluence of the critical branchings. The analysis of local confluence of rewriting systems on algebraic structures, such as groups or linear algebras, is complicated because of the underlying algebraic axioms. This article introduces the structure of algebraic polygraph modulo that formalizes the interaction between the rules of an algebraic rewriting system and the inherent algebraic axioms, and we show a critical branching lemma for algebraic polygraphs. We deduce a critical branching lemma for rewriting systems on algebraic models whose axioms are specified by convergent modulo rewriting systems. We illustrate our constructions for string, linear, and group rewriting systems.
Open field stress testing: finally an optimal method in young children? Reference values for mobile cardiopulmonary exercise testing in healthy children aged 4–8 years
Authors: Kalden Philipp , Schoeffl Isabelle , Rottermann Kathrin , Loeffelbein Florian , Michaelis Anna , Markel Franziska , Brosig Susann , Gebauer Roman Antonin , Daehnert Ingo , Paech Christian
Published: December 2021

Introduction:

Cardiopulmonary exercise testing represents the diagnostic tool for determining cardiopulmonary function. Especially in small children, exercise testing is extremely challenging. To address this problem, field testing has been implemented using small mobile devices. This study aims at using this protocol for developing normal values for cardiopulmonary exercise testing in very young children.

Material and methods:

Healthy children aged 4–8 years were recruited. All children were tested according to an outdoor protocol, in which they were instructed to walk, then run slowly, then a little harder and at last run at full speed. Each step lasted for 2 minutes, except the last step, in which the children were instructed to maintain as long as possible.

Results:

A total of 104 children (64 female/35 male, mean age 6.6 years) performed outdoor cardiopulmonary exercise testing using a mobile device. Almost all tests were completed successfully (95%). Despite a predominance of female study subjects, anthropometric values did not differ between boys and girls. V̇O2peak/kg, respiratory exchange ratio, VT1, heart rate at VT1, and time of exercise were also comparable between sexes. Generally, a tendency of higher maximal oxygen uptake could be observed in older children.

Conclusion:

Open field mobile cardiopulmonary exercise testing represents a novel approach in very young children. In this study, we were able to determine normal values of maximal oxygen uptake and OUES/kg for 4–8-year-old children. The method is easy to achieve and safe.
Consumer demand for novel fruit and vegetable products with extended shelf lives in East Africa: a multinational multi-product analysis
Authors: Tepe Johanna , Benali Marwan , Lemken Dominic
Published: December 2021

Objective:

To evaluate the potential of products made out of underutilised fruits and vegetables for closing seasonal nutritional gaps among rural and urban consumers in East Africa.

Design:

The multinational analysis combines sensory testing and experimental auctions to assess consumers’ perceptions and willingness to pay (WTP) for 6 different fruit and vegetable products.

Setting:

Open markets in rural and urban areas in Kenya, Tanzania and Uganda.

Participants:

There were 939 male and female adults who were at least 18 years old.

Results:

Tobit models for each product show that besides sensory perception, similar socio-demographic characteristics influence consumers’ WTP for these products in all 3 countries. The products are especially liked among younger, male and urban consumers.

Conclusion:

We conclude that there is demand and a potential market for processed fruit and vegetable products based on indigenous raw material in East Africa. The products, thus, have promising potential to improve nutrition, especially during off-season conditions when access to fresh produce is limited.
Association between iron supplementation and the presence of diarrhoea in Peruvian children aged 6–59 months: analysis of the database of the Demographic and Family Health Survey in Peru (DHS, Peru), years 2009–2019
Authors: Valverde-Bruffau Valeria Janice , Steenland Kyle , Gonzales Gustavo F
Published: December 2021

Introduction:

According to the WHO, anaemia is a severe public health problem when the prevalence is ≥ 40 %. In 2019, in Peru, 40·1 % of children (aged 6 to 35 months) are diagnosed as anaemic. This is a concern since, despite the efforts of the governments to reduce the prevalence, the problem has stagnated since 2011. The treatment applied to deal with anaemia is Fe supplementation. Although Fe is essential for cell function, an excess can produce adverse responses, such as gut inflammation affecting microbiota and resulting in diarrhoeic episodes.

Objective:

To determine the association between diarrhoea and Fe supplementation in children with and without anaemia, controlling for different socio-demographic variables.

Design:

We conducted via logistic regression to obtain diarrhoea prevalence ratios (PR), adjusted by age, sex, geographic region, water and sanitation service, and rurality. The survey asked for recent episodes of diarrhoea during the last 7 d; similarly, after the consumption of Fe supplements during the last 12 months before the survey.

Setting:

Peru.

Participants:

The Demographic and Family Health Survey (DHS) is conducted annually at home among 14 202 children on average (2009–2019).

Results:

Fe supplementation in the last 7 d (PR = 1·09) or the last 12 months (PR = 1·19) (P< 0·0001) was associated with an increased risk of diarrhoea. The same association was observed between Fe supplementation and the presence of anaemia.

Conclusions:

Fe supplementation is associated with diarrhoea and overuse in children should be avoided.
Fast Improvement of TEM Images with Low-Dose Electrons by Deep Learning
Authors: Katsuno Hiroyasu , Kimura Yuki , Yamazaki Tomoya , Takigawa Ichigaku
Published: December 2021

Low electron dose observation is indispensable for observing various samples using a transmission electron microscope; consequently, image processing has been used to improve transmission electron microscopy (TEM) images. To apply such image processing to in situ observations, we here apply a convolutional neural network to TEM imaging. Using a dataset that includes short-exposure images and long-exposure images, we develop a pipeline for processed short-exposure images, based on end-to-end training. The quality of images acquired with a total dose of approximately $5$$e^{-}$ per pixel becomes comparable to that of images acquired with a total dose of approximately $1{,}000$$e^{-}$ per pixel. Because the conversion time is approximately 8 ms, in situ observation at 125 fps is possible. This imaging technique enables in situ observation of electron-beam-sensitive specimens.
Patterns of care and clinical outcomes in stage IVA cervical cancer: 14-year experience from a tertiary care centre in South India
Authors: John Neenu Oliver , Sathyamurthy Arvind , Prasoona Shanthi , Ramireddy Jeba Karunya , Rebekah Grace , Das Saikat , George Reena Mary , John Subhashini , Ram Thomas Samuel
Published: December 2021

Aim:

To analyse the patterns of care and clinical outcomes of patients diagnosed with cervical cancer International Federation of Gynecology and Obstetrics (FIGO) stage IVA treated at a tertiary care centre in South India.

Materials and methods:

The electronic medical records of 2,476 patients diagnosed with cervical cancer at a tertiary care institution between January 2005 and December 2018 were reviewed. Among them, 96 patients diagnosed with histologically proven carcinoma cervix stage IVA established by either cystoscopy or proctoscopy were included. Four patients who did not receive treatment at the study centre were excluded and 92 patients were available for final analysis.

Results:

The median follow-up period was 12 months (2–131 months). Of the 92 patients, 59 patients (64·13%) received radiation therapy (RT) alone, 22 patients (23·9%) received chemoradiation (CRT), three patients (3·26%) received neoadjuvant chemotherapy (NACT) followed by RT, one (1·08%) received NACT followed by CRT, four patients (4·35%) received chemotherapy alone, while three (3·26%) were offered best supportive care. The median progression-free survival (PFS) was 12 months (95% CI: 9·6–14·4 months) and median overall survival (OS) was 25 months (95% CI: 16·6–33·4 months). The 2-year and 3-year PFS was 30 and 20%, respectively, and the OS was 50 and 32%, respectively.

Conclusion:

The management of stage IVA cervical cancer needs to be individualised to achieve a fine balance between local control, toxicity, and quality of life. RT is the mainstay of treatment with concurrent chemotherapy in carefully selected patients. Involvement of palliative care team early in the course of treatment adds a holistic approach to the continuum of oncological care.
Adaptives Testen von Textverständnis in der Grundschule
Authors: Ludewig Ulrich , Trendtel Matthias , Schlitter Theresa , McElvany Nele
Published: December 2021

Zusammenfassung. Die vorliegende Studie befasst sich mit Entwicklung eines Itempools für einen computeradaptiver Test (CAT) zur Erfassung von Textverständnis in der Grundschule. Der Effizienzgewinn von CATs im Vergleich zu Tests mit festgelegter Itemabfolge (FITs) wird untersucht. Für die Kalibrierung eines Textverständnisitempools wurden Stichproben von N = 1 975 Schülerinnen und Schülern aus der 3. und 4. Klassenstufe erhoben. Der finale Itempool umfasst 132 auf Messgüte geprüfte Items. Eine CAT Simulation mit 25 Items zeigte, dass ein CAT das Textverständnis mit sehr guter Reliabilität ( Releap ≈ .92) erfassen kann. Ein CAT mit 8 Items erreichte eine gute Reliabilität ( Releap ≈ .80). Analysen zur Konstruktvalidierung werden berichtet. Ein CAT basierend auf dem Itempool misst bis zu 19 % effizienter als ein vergleichbarer FIT und wäre besonders für die Erfassung von Textverständnis bei Schülerinnen und Schülern eines breiten Leistungsspektrums und für die Lernverlaufsdiagnostik geeignet.
Some Lava Flows May Not Have Been as Thick as They Appear
Authors: Katona Jonas , Fu Xiaojing , Mittal Tushar , Manga Michael , Self Stephen
Published: December 2021

Individual lava flows in flood basalt provinces are composed of sheet pāhoehoe lobes and the 10–100 m thick lobes are thought to form by inflation. Quantifying the emplacement history of these lobes can help infer the magnitude and temporal dynamics of prehistoric eruptions. Here we use a phase‐field model to describe solidification and remelting of sequentially emplaced lava lobes to explore additional processes that may lead to thick flows and lobes. We calibrate parameters using field measurements at Makaopuhi lava lake. We vary the lobe thicknesses and the time interval between eruptions to study the interplay between these factors and their impact on the thermal evolution of flows. Our analysis shows that if the time between emplacements is sufficiently short, remelting may merge sequentially emplaced lobes—making lava flows appear thicker than they actually were—which suggests that fused lobes could be another mechanism that creates apparently thick lava flows.
Nitrous Oxide Emissions From Drying Streams and Rivers
Authors: Tonina D. , Marzadri A. , Bellin A. , Dee M. M. , Bernal S. , Tank J. L.
Published: December 2021

Streams and rivers are suffering more extreme and prolonged low flows than those naturally occurring without human intervention with potential relevant worldwide effects on the production of nitrous oxide (N2O), a greenhouse gas 300 times more potent than carbon dioxide. Here, we address the question of whether droughts and management‐induced low flows increase riverine N2O emissions causing positive feedback in response to climate change. Supported by field data, we model riverine N2O emissions for decreasing mean summer flows in a forested and agricultural watershed under chemostatic and chemodynamic dissolved inorganic reactive nitrogen (DIN) concentrations. Our results demonstrate that total N2O emissions decrease with increasing low flow severity in both watersheds regardless of DIN scenario; which imparts a form of climate resilience.
Biased Estimates of Equilibrium Climate Sensitivity and Transient Climate Response Derived From Historical CMIP6 Simulations
Authors: Dong Yue , Armour Kyle C. , Proistosescu Cristian , Andrews Timothy , Battisti David S. , Forster Piers M. , Paynter David , Smith Christopher J. , Shiogama Hideo
Published: December 2021

This study assesses the effective climate sensitivity (EffCS) and transient climate response (TCR) derived from global energy budget constraints within historical simulations of eight CMIP6 global climate models (GCMs). These calculations are enabled by use of the Radiative Forcing Model Intercomparison Project (RFMIP) simulations, which permit accurate quantification of the radiative forcing. Long‐term historical energy budget constraints generally underestimate EffCS from CO2 quadrupling and TCR from CO2 ramping, owing to changes in radiative feedbacks and changes in ocean heat uptake efficiency. Atmospheric GCMs forced by observed warming patterns produce lower values of EffCS that are more in line with those inferred from observed historical energy budget changes. The differences in the EffCS estimates from historical energy budget constraints of models and observations are traced to discrepancies between modeled and observed historical surface warming patterns.
Hysteresis of the Glacial Atlantic Meridional Overturning Circulation Controlled by Thermal Feedbacks
Authors: Ando Taigo , Oka Akira
Published: December 2021

The multiple equilibrium behavior of the Atlantic meridional overturning circulation (AMOC) is related to the mode transition of the AMOC, which played an important role in abrupt glacial climate changes. However, the difference between modern and glacial climates is not well understood. Here, we examined the structure of the multiple equilibria of the AMOC under the modern and glacial climates through hysteresis experiments using an earth system model of intermediate complexity. The glacial AMOC exhibited a shallower AMOC mode but not the off mode, and a narrower range of multiple equilibria than the modern AMOC. This glacial hysteresis behavior occurred associated with a shift of deep water formation due to changes in surface air temperature and sea ice, whereas that of the modern AMOC is attributed to the basin‐scale salinity feedback. These features were commonly found in two glacial simulations with different strengths of the AMOC at the Last Glacial Maximum.
Event‐Based Training in Label‐Limited Regimes
Authors: Linville Lisa M.
Published: December 2021

The distribution of attributes assigned using data on independent sensors for a specific source, for example, magnitude, can be richly descriptive for final event characterization and associated uncertainty. Attribute distributions can also provide powerful context for event characterization in the absence of comprehensive annotation. This work develops a way to leverage distributional information across a set of sensors in the absence of comprehensive annotation as a domain‐informed regularization term applied during gradient‐based learning. The regularization term is the basis of event‐based training which I show can be a powerful semi‐supervised learning (SSL) approach. I first use a simple feed forward neural network and a toy data set to outline how data set structure interacts with the assumptions inherent to many semi‐supervised learning approaches. I then demonstrate the effectiveness of event‐based training using a deep convolutional neural network for seismic event classification in Utah, which increases SSL accuracy from 92% to 97% on event classification with a limited number of training labels.
Mesoscale Convective Systems in a Superparameterized E3SM Simulation at High Resolution
Authors: Lin Guangxing , Jones Christopher R. , Leung L. Ruby , Feng Zhe , Ovchinnikov Mikhail
Published: December 2021

Accurately representing mesoscale convective systems (MCSs) is crucial to simulating the energy and water cycles in global climate models. Using a novel MCS identification and tracking algorithm applied to observations and model simulations, we evaluate how well the Energy Exascale Earth System Model (E3SM) simulates MCSs over the central US. Simulations performed by E3SM at 25 km grid spacing with and without superparameterization (SP) are compared and evaluated against observations using multiple metrics highlighting important MCS characteristics. Compared to E3SM, the superparameterized model (SP‐E3SM) better simulates MCS number and MCS precipitation amount, diurnal cycle, propagation, and the probability distribution of precipitation rate in both spring and summer. The improvement from SP is partly contributed by improvement in simulating the large‐scale environments, featuring enhanced atmospheric low‐level moisture and larger moisture transport to the central US relative to E3SM. However, SP‐E3SM still underestimates MCS precipitation amount, particularly in summer. This underestimation is closely related to the negative bias in MCS precipitation intensity, although the drier environments simulated during summer also contributes to underestimation of MCS frequency. Without SP, the larger bias in MCS precipitation amount is closely related to the negative bias in MCS frequency, while the substantial dry bias in the large‐scale environments also contributes to underestimation of MCS intensity. Our results suggest that SP improves MCS simulation by improving modeling of the large‐scale environments and convection initiation, which are both major limiting factors in E3SM even at 25 km grid spacing where deep convection is represented by a cumulus parameterization.
Circular RNA circCCNT2 is upregulated in the anterior cingulate cortex of individuals with bipolar disorder
Authors: Lin Rixing , Lopez Juan Pablo , Cruceanu Cristiana , Pierotti Caroline , Fiori Laura M. , Squassina Alessio , Chillotti Caterina , Dieterich Christoph , Mellios Nikolaos , Turecki Gustavo
Published: December 2021

Gene expression dysregulation in the brain has been associated with bipolar disorder, but little is known about the role of non-coding RNAs. Circular RNAs are a novel class of long noncoding RNAs that have recently been shown to be important in brain development and function. However, their potential role in psychiatric disorders, including bipolar disorder, has not been well investigated. In this study, we profiled circular RNAs in the brain tissue of individuals with bipolar disorder. Total RNA sequencing was initially performed in samples from the anterior cingulate cortex of a cohort comprised of individuals with bipolar disorder (N = 13) and neurotypical controls (N = 13) and circular RNAs were identified and analyzed using “circtools”. Significant circular RNAs were validated by RT-qPCR and replicated in the anterior cingulate cortex in an independent cohort (24 bipolar disorder cases and 27 controls). In addition, we conducted in vitro studies using B-lymphoblastoid cells collected from bipolar cases (N = 19) and healthy controls (N = 12) to investigate how circular RNAs respond following lithium treatment. In the discovery RNA sequencing analysis, 26 circular RNAs were significantly differentially expressed between bipolar disorder cases and controls (FDR < 0.1). Of these, circCCNT2 was RT-qPCR validated showing significant upregulation in bipolar disorder (p = 0.03). This upregulation in bipolar disorder was replicated in an independent post-mortem human anterior cingulate cortex cohort and in B-lymphoblastoid cell culture. Furthermore, circCCNT2 expression was reduced in response to lithium treatment in vitro. Together, our study is the first to associate circCCNT2 to bipolar disorder and lithium treatment.
Brain network coupling associated with cognitive performance varies as a function of a child’s environment in the ABCD study
Authors: Ellwood-Lowe Monica E. , Whitfield-Gabrieli Susan , Bunge Silvia A.
Published: December 2021

Prior research indicates that lower resting-state functional coupling between two brain networks, lateral frontoparietal network (LFPN) and default mode network (DMN), relates to cognitive test performance, for children and adults. However, most of the research that led to this conclusion has been conducted with non-representative samples of individuals from higher-income backgrounds, and so further studies including participants from a broader range of socioeconomic backgrounds are required. Here, in a pre-registered study, we analyzed resting-state fMRI from 6839 children ages 9–10 years from the ABCD dataset. For children from households defined as being above poverty (family of 4 with income > $25,000, or family of 5+ with income > $35,000), we replicated prior findings; that is, we found that better performance on cognitive tests correlated with weaker LFPN-DMN coupling. For children from households defined as being in poverty, the direction of association was reversed, on average: better performance was instead directionally related to stronger LFPN-DMN connectivity, though there was considerable variability. Among children in households below poverty, the direction of this association was predicted in part by features of their environments, such as school type and parent-reported neighborhood safety. These results highlight the importance of including representative samples in studies of child cognitive development.
Influence of the chirality of carbon nanodots on their interaction with proteins and cells
Authors: Yan Huijie , Cacioppo Michele , Megahed Saad , Arcudi Francesca , Đorđević Luka , Zhu Dingcheng , Schulz Florian , Prato Maurizio , Parak Wolfgang J. , Feliu Neus
Published: December 2021

Carbon nanodots with opposite chirality possess the same major physicochemical properties such as optical features, hydrodynamic diameter, and colloidal stability. Here, a detailed analysis about the comparison of the concentration of both carbon nanodots is carried out, putting a threshold to when differences in biological behavior may be related to chirality and may exclude effects based merely on differences in exposure concentrations due to uncertainties in concentration determination. The present study approaches this comparative analysis evaluating two basic biological phenomena, the protein adsorption and cell internalization. We find how a meticulous concentration error estimation enables the evaluation of the differences in biological effects related to chirality.
Computational mechanisms of distributed value representations and mixed learning strategies
Authors: Farashahi Shiva , Soltani Alireza
Published: December 2021

Learning appropriate representations of the reward environment is challenging in the real world where there are many options, each with multiple attributes or features. Despite existence of alternative solutions for this challenge, neural mechanisms underlying emergence and adoption of value representations and learning strategies remain unknown. To address this, we measure learning and choice during a multi-dimensional probabilistic learning task in humans and trained recurrent neural networks (RNNs) to capture our experimental observations. We find that human participants estimate stimulus-outcome associations by learning and combining estimates of reward probabilities associated with the informative feature followed by those of informative conjunctions. Through analyzing representations, connectivity, and lesioning of the RNNs, we demonstrate this mixed learning strategy relies on a distributed neural code and opponency between excitatory and inhibitory neurons through value-dependent disinhibition. Together, our results suggest computational and neural mechanisms underlying emergence of complex learning strategies in naturalistic settings.
Dynamic regulation of N6,2′-O-dimethyladenosine (m6Am) in obesity
Authors: Ben-Haim Moshe Shay , Pinto Yishay , Moshitch-Moshkovitz Sharon , Hershkovitz Vera , Kol Nitzan , Diamant-Levi Tammy , Beeri Michal Schnaider , Amariglio Ninette , Cohen Haim Y. , Rechavi Gideon
Published: December 2021

The prevalent m6Am mRNA cap modification was recently identified as a valid target for removal by the human obesity gene FTO along with the previously established m6A mRNA modification. However, the deposition and dynamics of m6Am in regulating obesity are unknown. Here, we investigate the liver m6A/m methylomes in mice fed on a high fat Western-diet and in ob/ob mice. We find that FTO levels are elevated in fat mice, and that genes which lost m6Am marking under obesity are overly downregulated, including the two fatty-acid-binding proteins FABP2, and FABP5. Furthermore, the cellular perturbation of FTO correspondingly affect protein levels of its targets. Notably, generally m6Am- but not m6A-methylated genes, are found to be highly enriched in metabolic processes. Finally, we deplete all m6A background via Mettl3 knockout, and unequivocally uncover the association of m6Am methylation with increased mRNA stability, translation efficiency, and higher protein expression. Together, these results strongly implicate a dynamic role for m6Am in obesity-related translation regulation.
Tribo-electrochemistry induced artificial solid electrolyte interface by self-catalysis
Authors: Qin Chichu , Wang Dong , Liu Yumin , Yang Pengkun , Xie Tian , Huang Lu , Zou Haiyan , Li Guanwu , Wu Yingpeng
Published: December 2021

Potassium (K) metal is a promising alkali metal anode for its high abundance. However, dendrite on K anode is a serious problem which is even worse than Li. Artificial SEI (ASEI) is one of effective routes for suppressing dendrite. However, there are still some issues of the ASEI made by the traditional methods, e.g. weak adhesion, insufficient/uneven reaction, which deeply affects the ionic diffusion kinetics and the effect of inhibiting dendrites. Herein, through a unique self-catalysis tribo-electrochemistry reaction, a continuous and compact protective layer is successfully constructed on K metal anode in seconds. Such a continuous and compact protective layer can not only improve the K+ diffusion kinetics, but also strongly suppress K dendrite formation by its hard mechanical properties derived from rigid carbon system, as well as the improved K+ conductivity and lowered electronic conductivity from the amorphous KF. As a result, the potassium symmetric cells exhibit stable cycles last more than 1000 h, which is almost 500 times that of pristine K.
KDM6B promotes activation of the oncogenic CDK4/6-pRB-E2F pathway by maintaining enhancer activity in MYCN-amplified neuroblastoma
Authors: D’Oto Alexandra , Fang Jie , Jin Hongjian , Xu Beisi , Singh Shivendra , Mullasseril Anoushka , Jones Victoria , Abu-Zaid Ahmed , von Buttlar Xinyu , Cooke Bailey , Hu Dongli , Shohet Jason , Murphy Andrew J. , Davidoff Andrew M. , Yang Jun
Published: December 2021

The H3K27me2/me3 histone demethylase KDM6B is essential to neuroblastoma cell survival. However, the mechanism of KDM6B action remains poorly defined. We demonstrate that inhibition of KDM6B activity 1) reduces the chromatin accessibility of E2F target genes and MYCN, 2) selectively leads to an increase of H3K27me3 but a decrease of the enhancer mark H3K4me1 at the CTCF and BORIS binding sites, which may, consequently, disrupt the long-range chromatin interaction of MYCN and E2F target genes, and 3) phenocopies the transcriptome induced by the specific CDK4/6 inhibitor palbociclib. Overexpression of CDK4/6 or Rb1 knockout confers neuroblastoma cell resistance to both palbociclib and the KDM6 inhibitor GSK-J4. These data indicate that KDM6B promotes an oncogenic CDK4/6-pRB-E2F pathway in neuroblastoma cells via H3K27me3-dependent enhancer-promoter interactions, providing a rationale to target KDM6B for high-risk neuroblastoma.
KRas-transformed epithelia cells invade and partially dedifferentiate by basal cell extrusion
Authors: Fadul John , Zulueta-Coarasa Teresa , Slattum Gloria M. , Redd Nadja M. , Jin Mauricio Franco , Redd Michael J. , Daetwyler Stephan , Hedeen Danielle , Huisken Jan , Rosenblatt Jody
Published: December 2021

Metastasis is the main cause of carcinoma-related death, yet we know little about how it initiates due to our inability to visualize stochastic invasion events. Classical models suggest that cells accumulate mutations that first drive formation of a primary mass, and then downregulate epithelia-specific genes to cause invasion and metastasis. Here, using transparent zebrafish epidermis to model simple epithelia, we can directly image invasion. We find that KRas-transformation, implicated in early carcinogenesis steps, directly drives cell invasion by hijacking a process epithelia normally use to promote death—cell extrusion. Cells invading by basal cell extrusion simultaneously pinch off their apical epithelial determinants, endowing new plasticity. Following invasion, cells divide, enter the bloodstream, and differentiate into stromal, neuronal-like, and other cell types. Yet, only invading KRasV12 cells deficient in p53 survive and form internal masses. Together, we demonstrate that KRas-transformation alone causes cell invasion and partial dedifferentiation, independently of mass formation.
Molecular basis of enzymatic nitrogen-nitrogen formation by a family of zinc-binding cupin enzymes
Authors: Zhao Guiyun , Peng Wei , Song Kaihui , Shi Jingkun , Lu Xingyu , Wang Binju , Du Yi-Ling
Published: December 2021

Molecules with a nitrogen-nitrogen (N-N) bond in their structures exhibit various biological activities and other unique properties. A few microbial proteins are recently emerging as dedicated N-N bond forming enzymes in natural product biosynthesis. However, the details of these biochemical processes remain largely unknown. Here, through in vitro biochemical characterization and computational studies, we report the molecular basis of hydrazine bond formation by a family of di-domain enzymes. These enzymes are widespread in bacteria and sometimes naturally exist as two standalone enzymes. We reveal that the methionyl-tRNA synthase-like domain/protein catalyzes ATP-dependent condensation of two amino acids substrates to form a highly unstable ester intermediate, which is subsequently captured by the zinc-binding cupin domain/protein and undergoes redox-neutral intramolecular rearrangement to give the N-N bond containing product. These results provide important mechanistic insights into enzymatic N-N bond formation and should facilitate future development of novel N-N forming biocatalyst.
The methyltransferase METTL3 negatively regulates nonalcoholic steatohepatitis (NASH) progression
Authors: Li Xinzhi , Yuan Bingchuan , Lu Min , Wang Yuqin , Ding Na , Liu Chunhong , Gao Ming , Yao Zhicheng , Zhang Shiyan , Zhao Yujun , Xie Liwei , Chen Zheng
Published: December 2021

Nonalcoholic steatohepatitis (NASH) is a key step in the progression of nonalcoholic fatty liver (NAFL) to cirrhosis. However, the molecular mechanisms of the NAFL-to-NASH transition are largely unknown. Here, we identify methyltransferase like 3 (METTL3) as a key negative regulator of NASH pathogenesis. Hepatocyte-specific deletion of Mettl3 drives NAFL-to-NASH progression by increasing CD36-mediated hepatic free fatty acid uptake and CCL2-induced inflammation, which is due to increased chromatin accessibility in the promoter region of Cd36 and Ccl2. Antibody blockade of CD36 and CCL2 ameliorates NASH progression in hepatic Mettl3 knockout mice. Hepatic overexpression of Mettl3 protects against NASH progression by inhibiting the expression of CD36 and CCL2. Mechanistically, METTL3 directly binds to the promoters of the Cd36 and Ccl2 genes and recruits HDAC1/2 to induce deacetylation of H3K9 and H3K27 in  their promoters, thus suppressing Cd36 and Ccl2 transcription. Furthermore, METTL3 is translocated from the nucleus to the cytosol in NASH, which is associated with CDK9-mediated phosphorylation of METTL3. Our data reveal a mechanism by which METTL3 negatively regulates hepatic Cd36 and Ccl2 gene transcription via a histone modification pathway for protection against NASH progression.
Robustly printable freeform thermal metamaterials
Authors: Sha Wei , Xiao Mi , Zhang Jinhao , Ren Xuecheng , Zhu Zhan , Zhang Yan , Xu Guoqiang , Li Huagen , Liu Xiliang , Chen Xia , Gao Liang , Qiu Cheng-Wei , Hu Run
Published: December 2021

Thermal metamaterials have exhibited great potential on manipulating, controlling and processing the flow of heat, and enabled many promising thermal metadevices, including thermal concentrator, rotator, cloak, etc. However, three long-standing challenges remain formidable, i.e., transformation optics-induced anisotropic material parameters, the limited shape adaptability of experimental thermal metadevices, and a priori knowledge of background temperatures and thermal functionalities. Here, we present robustly printable freeform thermal metamaterials to address these long-standing difficulties. This recipe, taking the local thermal conductivity tensors as the input, resorts to topology optimization for the freeform designs of topological functional cells (TFCs), and then directly assembles and prints them. Three freeform thermal metadevices (concentrator, rotator, and cloak) are specifically designed and 3D-printed, and their omnidirectional concentrating, rotating, and cloaking functionalities are demonstrated both numerically and experimentally. Our study paves a powerful and flexible design paradigm toward advanced thermal metamaterials with complex shapes, omnidirectional functionality, background temperature independence, and fast-prototyping capability.