bluuebunny/crossref_metadata_2025 huggingface dataset:
Factors affecting contraceptive use among currently married women in Iraq in 2018
Authors: Abdelaziz Wafaa , Nofal Zohdy , Al-neyazy Suhair
Published: March 2022

Level of contraceptive use is one of the primary proximate determinants of fertility level. Among Arab countries, Iraq experiences high fertility rates, especially among adolescents. According to the 2018 Iraq Multiple Indicator Cluster Survey (IMICS 2018), 52.8% of currently married Iraqi women used a contraceptive method (36.1% used modern methods, and 16.7% used traditional methods). A multiple multinomial logistic regression model was adopted to investigate the demographic, socioeconomic, fertility, and cultural determinants of contraceptive use among currently married, nonpregnant Iraqi women based on the 2018 Iraq Multiple Indicator Cluster Survey data. The main findings indicated that women using modern contraceptive methods had more children, did not experience the death of a child, and had no desire for more children. Moreover, they were married before age 21, had at least an upper secondary education, had access to mass media, used the internet, belonged to a low or middle wealth category, and lived in urban Kurdistan. Kurdish women prefer to use traditional methods. The results suggest that family planning programmes should target women who live in southern/central areas of Iraq, as they were the least likely to use contraceptives, and motivate Kurdish women to use modern contraceptives rather than traditional contraceptives.
Blood calcium dynamics in cows receiving an aqueous calcium suspension for voluntary consumption or a calcium bolus following parturition
Authors: Wilms Juliette N. , Daniel Jean-Baptiste , Martín-Tereso Javier , Klop Arie , Goselink Roselinde , Han Yanming , van Kuijk Sandra
Published: March 2022

The form of oral calcium (Ca) supplement and the Ca source influence Ca absorption dynamics resulting in different postpartum calcemia. The objective of this study was to investigate whether an oral Ca supplement (mainly CaCO3) offered for voluntary consumption would maintain or increase postpartum blood Ca to the same degree as a Ca bolus (mainly CaCl2) providing an equivalent dose of a Ca. A total of 72 Holstein cows were blocked by expected parturition date and parity. Within each block of 3 animals, cows were randomly assigned to one of three treatments, including an oral Ca supplement offered for voluntary consumption (Ca-drink, n = 23), an oral Ca bolus (Ca-bolus, n = 24), or an untreated group (CON, n = 25). Treatments were administered once within 15 min postpartum. The Ca-drink provided 45 g of Ca (CaCO3 source) and was mixed in 20 L of lukewarm water and offered to cows for 30 min. The Ca-bolus provided 43 g of Ca (71% from CaCl2 and 29% from CaSO4) and was administered once. Both Ca-bolus and CON cows received 20-l of lukewarm water at parturition to standardize the volume of fluids (Ca-drink or 20-l lukewarm water) offered at parturition. Dairy cows offered Ca-drink had a 28% higher fluid consumption than Ca-bolus and CON cows. Milk yield and milk composition expressed in percentage protein, fat, lactose, and urea did not differ, whilst there was a small but significant increase in DMI in cows receiving the Ca-drink compared to CON, while Ca-bolus did not differ from other groups. This was consistent with reduced BW losses between week 1 and 3 in cows receiving the Ca-drink suspension. Treatment by time interactions were present for blood Ca, glucose, and urea concentrations. Blood Ca was relatively stable in Ca-drink cows, while higher fluctuations were observed in Ca-bolus cows. In Ca-bolus cows, blood Ca increased from 15 min to 6 h, decreased from 6 to 24 h, and finally increased again from 24 to 48 h. At 24 h post administration, blood Ca was greater in cows receiving the Ca-drink than cows receiving the Ca-bolus. Blood glucose was greater in Ca-bolus cows at 15 min after treatment administration compared with Ca-bolus and CON, while blood urea was higher in CON than Ca-drink and Ca-bolus throughout the sampling period. These results indicate that voluntary oral Ca resulted in a relatively stable calcemia, whereas higher fluctuations were observed in cows receiving the Ca-bolus. Due to a lack of differences between Ca-drink and Ca-bolus compared with CON, it is not possible to conclude regarding the efficacy in maintaining postpartum blood Ca.
De Hemptinne, the Benedictines and Catholic Assimilation on the Congolese Copperbelt, 1911–1960
Authors: LOFFMAN REUBEN A.
Published: March 2022

This article explores the history of the Benedictines in south-eastern Congo. The Benedictine leader, Jean-Félix De Hemptinne, eschewed an adaptationist approach to his mission work in favour of an assimilationist one. This article explains why he was able to follow such an approach for so long. Two factors were paramount. First, what Chris Bayly described as ‘lateral connections’ enabled De Hemptinne to side-step the need to engage meaningfully with local agricultural knowledge. Secondly, De Hemptinne's close if turbulent relationship with the colonial state facilitated a supply of funds and African labour despite the difficulties the Benedictines had in converting local people.
Consolidating Product Lines via Mergers and Acquisitions: Evidence From the USPTO Trademark Data
Authors: Hsu Po-Hsuan , Li Kai , Liu Xing , Wu Hong
Published: March 2022

Using a new trademark-based product market competition measure and a novel trademark-merger data set over the period 1983–2016, we show that companies facing greater product market competition are more likely to be acquirers. We further show that postmerger, compared to their nonacquiring peers, acquirers consolidate their product offerings by discontinuing more existing product lines and developing fewer new product lines. Using a quasi-experiment based on bids withdrawn due to exogenous reasons helps us establish the causal effect of deal completion on product-market consolidation. We conclude that acquisitions create product market synergies by cutting overlapping product offerings to achieve cost efficiency.
A 5-year analysis of Candida bloodstream infections in the paediatric cardiovascular surgery ICU of a tertiary care centre
Authors: Karaağaç Aysu Türkmen , Şavluk Ömer Faruk , Yıldırım Ayşe İnci
Published: March 2022

Background:

Candida infections have become one of the most common causes of morbidity and mortality in paediatric ICUs, especially following complex surgeries, all over the world. Therefore, we conducted a 5-year analysis of Candida bloodstream infections in our tertiary paediatric cardiovascular surgery ICU.

Methods:

One thousand nine hundred and thirty four children, 0–16-year-old, who underwent paediatric cardiovascular surgery between January 2016–June 2021 were enrolled in this retrospective study. Blood cultures obtained from 1056 patients, who needed mechanical ventilation and indwelling devices longer than 5 days and had the signs of infection according to Center for Disease Control criteria, were evaluated. The isolated pathogens were recorded. 137 with Candida bloodstream infections were reanalysed for their age, weight, cardiac pathologies, duration of mechanical ventilation, hospitalisation and antibiotic use.

Results:

One hundred and thirty-seven out of one thousand and fifty six patients (12.9%) had Candida growth in their blood cultures. C. albicans (n: 50, 36.5%), C. parapsilosis (n: 20, 14.6%), C. tropicalis (n: 8, 5.8%), C. glabrata (n: 5, 3.7%), and other non-albicans Candida species (n: 54, 39.4%) were isolated. The patients with Candida bloodstream infections had lower age, longer duration of mechanical ventilation, longer length of hospital stay and antibiotic use (p-values<0.05). They had cardiac pathologies as atrioventricular septal defect (18.9%), transposition of great arteries (17.6%), tetralogy of Fallot (12.4%), transposition of great arteries + double outlet right ventricle, or total anomalous pulmonary venous return + atrioventricular septal defect (37.9%), and others. The Candida bloodstream infections mortality was 11.6% (16/137).

Conclusion:

The most common cause of Candida bloodstream infections in the last five years in our paediatric cardiovascular surgery ICU was non-albicans Candida species. Prolonged mechanical ventilation, hospitalisation and antibiotic use, low age, and weight were found as the main risk factors that raise the morbidity and mortality rates of Candida bloodstream infections.
Which Duration of Unemployment Benefits is Perceived as Being Just for Which Groups? Results from a Factorial Survey Experiment in Germany
Authors: Osiander Christopher , Senghaas Monika , Stephan Gesine , Struck Olaf , Wolff Richard
Published: March 2022

Welfare states allocate and redistribute resources across different groups. For the social legitimacy of welfare states, public support of redistributive processes and outcomes is crucial. An important aspect in this context is the deservingness or non-deservingness of benefit recipients from the perspective of those who both financially contribute to the system and potentially benefit from it. We invited a random sample of the German labour force to participate in an online-survey. Using a factorial survey experiment, we described fictitious unemployed persons with different attributes and asked survey participants on the just maximum benefit duration for each particular case. Judgements regarding just benefit durations vary along the criteria of reciprocity, control, attitude and need: Respondents grant longer unemployment benefits to older jobseekers, as well as to jobseekers who became involuntarily unemployed, had stable employment careers, have to care for the elderly or are sole earners in the household.
Unsolved problems and unwanted decision-making in the last year of life: A qualitative analysis of comments from bereaved caregivers
Authors: Knop Jannis , Dust Gloria , Kasdorf Alina , Schippel Nicolas , Rietz Christian , Strupp Julia , Voltz Raymond
Published: March 2022

Objectives

Patients in their last year of life, as well as their relatives, often feel that existent care structures of the healthcare system do not adequately address their individual needs and challenges. This study analyzes unmet needs in terms of unsolved problems and unwanted decision-making in the health and social care of patients in their last year of life from the perspective of bereaved caregivers.

Methods

This qualitative study is based on free-text comments from informal caregivers of deceased patients collected as part of the Last-Year-of-Life-Study-Cologne (LYOL-C) using a postal survey. With qualitative content analysis, a category system with main and subcategories was developed in a multi-step process.

Results

Free-text commentaries and demographic data were collected from 240 bereaved caregivers. Particularly outside of hospice and palliative care services, study participants addressed the following unsolved problems: poor communication with medical and nursing staff, insufficient professional support for informal caregivers, inadequate psycho-social support for patients, and poor management of pain and other symptoms. Respondents often stated that their relative had to be cared for and die outside their own home, which the relative did not want.

Significance of results

Our findings suggest the necessity for greater awareness of patients’ and their relatives’ needs in the last year of life. Addressing individual needs, integrating palliative and hospice care in acute hospitals and other healthcare structures, and identifying patients in their last year of life and their caregivers could help to achieve more targeted interventions and optimization of care.
Visions of the Arctic Future: Blending Computational Text Analysis and Structured Futuring to Create Story‐Based Scenarios
Authors: Keys P. W. , Meyer A. E.
Published: March 2022

The future of Arctic social systems and natural environments is highly uncertain. Climate change will lead to unprecedented phenomena in the pan‐Arctic region, such as regular shipping traffic through the Arctic Ocean, urban growth, military activity, expanding agricultural frontiers, and transformed Indigenous societies. While intergovernmental to local organizations have produced numerous synthesis‐based visions of the future, a challenge in any scenario exercise is capturing the “possibility” space of change. In this work, we employ a computational text analysis to generate unique thematic input for novel, story‐based visions of the Arctic. Specifically, we develop a corpus of more than 2,000 articles in publicly accessible, English‐language Arctic newspapers that discuss the future in the Arctic. We then perform a latent Dirichlet allocation, resulting in 10 distinct topics and sets of associated keywords. From these topics and keywords, we design ten story‐based scenarios employing the Mānoa mashup, science fiction prototyping, and other methods. Our results demonstrate that computational text analysis can feed directly into a creative futuring process, whereby the output stories can be traced clearly back to the original topics and keywords. We discuss our findings in the context of the broader field of Arctic scenarios and show that the results of this computational text analysis produce complementary stories to the existing scenario literature. We conclude that story‐based scenarios can provide vital texture toward understanding the myriad possible Arctic futures.
Seasonal and Multiyear Changes in CO2Degassing at Mammoth Mountain Explained by Solid‐Earth‐Driven Fault Valving
Authors: Hilley George E. , Lewicki Jennifer L. , Baden Curtis W.
Published: March 2022

Changes in CO2emissions from volcanoes may evidence volcanic unrest. We use a multiyear time series of CO2flux collected at the Horseshoe Lake Tree Kill area on Mammoth Mountain, CA, to understand processes that cause variations in flux from this system. Seasonal variations are systematically lowest during the winter months and reach maximum values during the summer season. A persistent ∼20% reduction in CO2flux occurred during the Spring of 2017, coincident with the emergence of the area from drought and earthquake swarms in Long Valley Caldera. We used continuous GNSS measurements to calculate seasonal strains and stresses across the Mammoth Mountain area, and resolved resultant stresses onto the Mammoth Mountain Fault, which appears to facilitate gas transport to the surface. The normal stress changes are consistent with seasonal and multiyear changes in CO2flux, suggesting that fault valving by solid earth processes can alter surface gas fluxes.
Possible Anthropogenic Enhancement of Precipitation in the Sahel‐Sudan Savanna by Remote Agricultural Irrigation
Authors: Zeng Yujin , Milly P. C. D. , Shevliakova Elena , Malyshev Sergey , van Huijgevoort M. H. J. , Dunne K. A.
Published: March 2022

The local climatic impacts of historical expansion of irrigation are substantial, but the distant impacts are poorly understood, and their governing mechanisms generally have not been rigorously analyzed. Our experiments with an earth‐system model suggest that irrigation in the Middle East and South Asia may enhance rainfall in a large portion of the Sahel‐Sudan Savanna (SSS) to an extent comparable and opposite to its suppression by other anthropogenic climate drivers during the last several decades. The enhancement arises through a reduction in the meridional gradient of moist static energy from the Sahara Desert to the tropical rainforests. An implication of this study is that remote irrigation is a possible factor affecting the risk of drought and famine and, thus, future water security in the SSS region.
Arctic Snow Depth, Ice Thickness, and Volume From ICESat‐2 and CryoSat‐2: 2018–2021
Authors: Kacimi Sahra , Kwok Ron
Published: March 2022

Using ICESat‐2 and CryoSat‐2 freeboards, we examine the variability of monthly Arctic sea ice snow depth, thickness and volume between October 2018 and April 2021. For the 3 years, satellite‐derived estimates captured a decrease in mean April snow depth (∼2.50 cm) and ice thickness (∼0.28 m) equivalent to an ice volume loss of ∼12.5%. Results show greater thinning of multiyear ice with an end‐of‐season thickness in 2021 that is lower by ∼16.1% (0.50 m), with negligible changes over first‐year ice. For the period, sea ice thickness estimates using snow depth from climatology result in thicker ice (by up to ∼0.22 m) with a smaller decrease in multiyear ice thickness (∼0.38 m). An 18‐year satellite record, since the launch of ICESat, points to a loss of ∼6,000 km3 or one‐third of the winter Arctic ice volume driven by decline in multiyear‐ice coverage in the multi‐decadal transition to a largely seasonal ice cover.
New Findings Relating Tidal Variability and Solar Activity in the Low Latitude MLT Region
Authors: Andrioli V. F. , Xu J. , Batista P. P. , Resende L. C. A. , Da Silva L. A. , Marchezi J. P. , Li H. , Wang C. , Liu Z. , Guharay A.
Published: March 2022

Mesospheric winds have been measured by meteor radar at Cachoeira Paulista (22.7°S; 45°W) since April 1999. The tidal components were analyzed over about 21 years of available data exhibiting an annual and semi‐annual variation. Amplitudes of meridional diurnal (semidiurnal) tide are on averaged 30% (28%) and the zonal ones are 14% (20%) stronger at solar minimum than at solar maximum. The anticorrelation between F10.7 cm solar flux and amplitudes of the semiannual oscillation of diurnal and semidiurnal tides is presented. Additionally, the sporadic E (Es) layers occurrence has an anti‐correlation with solar activity due to the tidal wind variation. A discussion about the physical mechanism is performed in terms of the particle precipitation during High‐Speed Stream (HSS) events according to the solar cycle. Finally, a superposed epoch analysis of the tidal amplitudes during the HSS events in 2018 is presented. And a slight increase in all tidal components is seen when the structure reached the Earth and in the following days showing that indeed the electron precipitation during HSS events affect the tidal amplitudes.
Uncovering the Controls on Fluvial Bedrock Erodibility and Knickpoint Expression: A High‐Resolution Comparison of Bedrock Properties Between Knickpoints and Non‐Knickpoint Reaches
Authors: Chilton Kristin D. , Spotila James A.
Published: March 2022

Bedrock erodibility exerts a fundamental control on fluvial incision, and therefore on the evolution of entire landscapes. However, the roles and relative significance of specific bedrock properties like rock strength and discontinuity spacing in setting erodibility remain poorly understood. As a result, erodibility is often overlooked or oversimplified in numerical and field‐based investigations of landscape evolution processes, leading to misinterpretation of channel profile convexities (i.e., knickpoints) in studies seeking to infer uplift or baselevel histories from longitudinal profile analyses. Here, we investigate the controls on fluvial bedrock erodibility and knickpoint expression by conducting detailed surveys of 21 lithologic knickpoints and non‐knickpoint reaches (representing end‐member bedrock erodibility cases) and corresponding bedrock properties from small channels in the south‐central Appalachian Mountains. We use binary logistic regression of field data to test the relative strength of rock strength and discontinuity spacing as predictors of knickpoint occurrence, and therefore their relative impact on fluvial bedrock erodibility. We find that discontinuity spacing more strongly influences bedrock erodibility in this setting, where both rock strength and discontinuity spacing vary widely, confirming for the first time quantitatively the hypothesis that discontinuities exert a dominant control on fluvial erodibility. We also find that knickpoint expression is unique to a given stratigraphic interval, implying that knickpoint morphology is intimately linked to local conditions and therefore effectively unpredictable without detailed field measurements. Finally, because all 21 of our study knickpoints occur within a single geologic unit, our results illustrate that intra‐unit heterogeneity must be accounted for when considering lithologic influence on channel profile convexities.
LOFAR Observations of Lightning Initial Breakdown Pulses
Authors: Liu Ningyu Y. , Scholten Olaf , Hare Brian M. , Dwyer Joseph R. , Sterpka Christopher F. , Kolmašová Ivana , Santolík Ondřej
Published: March 2022

This paper reports an observational study of lightning initial breakdown pulses (IBPs) using the low‐frequency array radio telescope and a broadband magnetic field sensor. The data show that the overall spatiotemporal evolution of the electrical breakdown causing an IBP is rather complex. During an IBP, spatially and temporally separated bursts of very high frequency (VHF) electromagnetic radiation occur in a volume on the order of 1003 m3, and they are coincident with brief magnetic field pulses, indicating that the location of the active breakdown region can change suddenly. Furthermore, recurrent breakdown activity is observed, especially at the location of the VHF burst. Interpreting each VHF burst as being generated by a corona burst, an IBP pulse appears to start off from an initial corona burst and subsequent corona bursts enhance it. We further suggest that the generation of IBPs likely involves multiple space stems/leaders and connections between them.
Glacier Surface Speed Variations on the Kenai Peninsula, Alaska, 2014–2019
Authors: Yang Ruitang , Hock Regine , Kang Shichang , Guo Wanqin , Shangguan Donghui , Jiang Zongli , Zhang Qibing
Published: March 2022

To characterize the spatiotemporal variations of glacier surface speed on the Kenai Peninsula, Alaska (∼3,900 km2), we derived 92 surface speed fields between October 2014 and December 2019 using intensity offset tracking on Sentinel‐1 data. On average, speeds are 50% greater in spring (March‐May) than the annual mean (69 m a−1) while winter speeds are close to the annual mean. While marine‐terminating glaciers have their maximum speed near the terminus, both land‐ and lake‐terminating glaciers flow fastest around the median glacier elevation. On average, the lake‐terminating and tidewater glaciers flow 1.7 and 2.3 times faster than the land‐terminating glaciers, respectively. Monthly variations over the 5‐year period are strikingly synchronous regardless of terminus type suggesting that regional‐scale meteorological drivers govern the temporal variability. Mean annual speeds fluctuate roughly ±10% of the period mean without an apparent trend. At lake‐terminating Bear Glacier, a short‐term tripling in ice speed in fall 2019 over the area below an ice‐dammed lake coincides with an observed glacier lake outburst flood (GLOF). An earlier GLOF caused a persistent breach of the beach barrier between the proglacial lake and ocean which likely led to overall speed‐up of the lower glacier part throughout 2019. A significant speedup was also observed at the lower part of the lake‐terminating Ellsworth Glacier and attributed to rapid glacier retreat and lake expansion, probably further amplified by the terminus area becoming buoyant and a large tabular iceberg breaking off. Our results highlight the impact of GLOFs and proglacial characteristics in spatial and temporal glacier speed variations.
SIAH1 reverses chemoresistance in epithelial ovarian cancer via ubiquitination of YBX-1
Authors: Gao Wujiang , Chen Lu , Lin Li , Yang Meiling , Li Taoqiong , Wei Hong , Sha Chunli , Xing Jie , Zhang Mengxue , Zhao Shijie , Chen Qi , Xu Wenlin , Li Yuefeng , Zhu Xiaolan
Published: March 2022

Chemoresistance is a severe outcome among patients with epithelial ovarian cancer (EOC) that leads to a poor prognosis. YBX-1 has been shown to cause treatment failure and cancer progression in EOC. However, strategies that directly target YBX-1 are not yet conceivable. Here, we identified that SIAH1 which was downregulated in chemoresistant EOC samples and cell lines functioned as novel E3 ligases to trigger degradation of YBX-1 at cytoplasm by RING finger domain. Mechanistic studies show that YBX-1 was ubiquitinated by SIAH1 at lys304 that lead to the instability of its target m5C-modified mRNAs, thus sensitized EOC cells to cDDP. Overexpression of SIAH1 enhanced the antitumor efficacy of cisplatin in vitro and in vivo, which were partially impaired by ectopic expression of YBX-1 or depletion of YBX-1 ubiquitination. In summary, our data identify the SIAH1/YBX-1 interaction as a therapeutic target for overcoming EOC chemoresistance.
Signaling pathways and targeted therapy for myocardial infarction
Authors: Zhang Qing , Wang Lu , Wang Shiqi , Cheng Hongxin , Xu Lin , Pei Gaiqin , Wang Yang , Fu Chenying , Jiang Yangfu , He Chengqi , Wei Quan
Published: March 2022

Although the treatment of myocardial infarction (MI) has improved considerably, it is still a worldwide disease with high morbidity and high mortality. Whilst there is still a long way to go for discovering ideal treatments, therapeutic strategies committed to cardioprotection and cardiac repair following cardiac ischemia are emerging. Evidence of pathological characteristics in MI illustrates cell signaling pathways that participate in the survival, proliferation, apoptosis, autophagy of cardiomyocytes, endothelial cells, fibroblasts, monocytes, and stem cells. These signaling pathways include the key players in inflammation response, e.g., NLRP3/caspase-1 and TLR4/MyD88/NF-κB; the crucial mediators in oxidative stress and apoptosis, for instance, Notch, Hippo/YAP, RhoA/ROCK, Nrf2/HO-1, and Sonic hedgehog; the controller of myocardial fibrosis such as TGF-β/SMADs and Wnt/β-catenin; and the main regulator of angiogenesis, PI3K/Akt, MAPK, JAK/STAT, Sonic hedgehog, etc. Since signaling pathways play an important role in administering the process of MI, aiming at targeting these aberrant signaling pathways and improving the pathological manifestations in MI is indispensable and promising. Hence, drug therapy, gene therapy, protein therapy, cell therapy, and exosome therapy have been emerging and are known as novel therapies. In this review, we summarize the therapeutic strategies for MI by regulating these associated pathways, which contribute to inhibiting cardiomyocytes death, attenuating inflammation, enhancing angiogenesis, etc. so as to repair and re-functionalize damaged hearts.
Potential educational and workforce strategies to meet the oral health challenges of an increasingly older population: a qualitative study
Authors: Prosser Georgina M. , Louca Chris , Radford David R.
Published: March 2022

Introduction

The demographic shift in the age profile of the UK is well established. Older people have more complex requirements to maintain their oral health.

Objectives

This research explored Gerodontology with influential and recognised UK experts in Dental Public Health, Dental Education and Gerodontology. Three main topics were explored: the dental challenges associated with the ageing population, the role of dental care professionals (DCPs) and the training of undergraduate dental professionals.

Methods

Quantitative data from the literature were used to develop a topic guide for semi-structured interviews with a purposeful sample of nine participants. Initial analysis of the qualitative data was undertaken using NVivo V12 software and themes were identified. Final themes and subthemes were confirmed after a series of remote round table discussions.

Results

Four themes and 14 subthemes were identified. These included disagreements and agreements, the challenges of providing dental care to the older adult population, and the delivery of dental care by the dental team and finally education. All participants had significant concerns about the oral and dental challenges of the older population.

Conclusions

The themes that emerged were complex and overlapping. Better utilisation of all members of the dental workforce was reported to be an essential approach, as was reorientation of existing care models with a focus on prevention. Regarding undergraduate education, the consensus was that the training was not adequate for both current and future needs.
Improved prediction of protein-protein interactions using AlphaFold2
Authors: Bryant Patrick , Pozzati Gabriele , Elofsson Arne
Published: March 2022

Predicting the structure of interacting protein chains is a fundamental step towards understanding protein function. Unfortunately, no computational method can produce accurate structures of protein complexes. AlphaFold2, has shown unprecedented levels of accuracy in modelling single chain protein structures. Here, we apply AlphaFold2 for the prediction of heterodimeric protein complexes. We find that the AlphaFold2 protocol together with optimised multiple sequence alignments, generate models with acceptable quality (DockQ ≥ 0.23) for 63% of the dimers. From the predicted interfaces we create a simple function to predict the DockQ score which distinguishes acceptable from incorrect models as well as interacting from non-interacting proteins with state-of-art accuracy. We find that, using the predicted DockQ scores, we can identify 51% of all interacting pairs at 1% FPR.
Estrogen receptor inhibition mediates radiosensitization of ER-positive breast cancer models
Authors: Michmerhuizen Anna R. , Lerner Lynn M. , Pesch Andrea M. , Ward Connor , Schwartz Rachel , Wilder-Romans Kari , Liu Meilan , Nino Charles , Jungles Kassidy , Azaria Ruth , Jelley Alexa , Zambrana Garcia Nicole , Harold Alexis , Zhang Amanda , Wharram Bryan , Hayes Daniel F. , Rae James M. , Pierce Lori J. , Speers Corey W.
Published: March 2022

Endocrine therapy (ET) is an effective first-line therapy for women with estrogen receptor-positive (ER + ) breast cancers. While both ionizing radiation (RT) and ET are used for the treatment of women with ER+ breast cancer, the most effective sequencing of therapy and the effect of ET on tumor radiosensitization remains unclear. Here we sought to understand the effects of inhibiting estrogen receptor (ER) signaling in combination with RT in multiple preclinical ER+ breast cancer models. Clonogenic survival assays were performed using variable pre- and post-treatment conditions to assess radiosensitization with estradiol, estrogen deprivation, tamoxifen, fulvestrant, or AZD9496 in ER+ breast cancer cell lines. Estrogen stimulation was radioprotective (radiation enhancement ratios [rER]: 0.51–0.82). Conversely, when given one hour prior to RT, ER inhibition or estrogen depletion radiosensitized ER+ MCF-7 and T47D cells (tamoxifen rER: 1.50–1.60, fulvestrant rER: 1.76–2.81, AZD9496 rER: 1.33–1.48, estrogen depletion rER: 1.47–1.51). Combination treatment resulted in an increase in double-strand DNA (dsDNA) breaks as a result of inhibition of non-homologous end joining-mediated dsDNA break repair with no effect on homologous recombination. Treatment with tamoxifen or fulvestrant in combination with RT also increased the number of senescent cells but did not affect apoptosis or cell cycle distribution. Using an MCF-7 xenograft model, concurrent treatment with tamoxifen and RT was synergistic and resulted in a significant decrease in tumor volume and a delay in time to tumor doubling without significant toxicity. These findings provide preclinical evidence that concurrent treatment with ET and RT may be an effective radiosensitization strategy.
Novel indolic AMPK modulators induce vasodilatation through activation of the AMPK–eNOS–NO pathway
Authors: Sanz-Gómez Marta , Aledavood Elnaz , Beroiz-Salaverri Marina , Lagartera Laura , Vega-Martín Elena , Gil-Ortega Marta , Cumella Jose , Pérez Concepción , Luque Francisco Javier , Estarellas Carolina , Fernández-Alfonso María S. , Castro Ana
Published: March 2022

Endothelial adenosine monophosphate-activated protein kinase (AMPK) plays a critical role in the regulation of vascular tone through stimulating nitric oxide (NO) release in endothelial cells. Since obesity leads to endothelial dysfunction and AMPK dysregulation, AMPK activation might be an important strategy to restore vascular function in cardiometabolic alterations. Here, we report the identification of a novel AMPK modulator, the indolic derivative IND6, which shows affinity for AMPKα1β1γ1, the primary AMPK isoform in human EA.Hy926 endothelial cells. IND6 shows inhibitory action of the enzymatic activity in vitro, but increases the levels of p-Thr174AMPK, p-Ser1177eNOS and p-Ser79ACC in EA.Hy926. This paradoxical finding might be explained by the ability of IND6 to act as a mixed-type inhibitor, but also to promote the enzyme activation by adopting two distinct binding modes at the ADaM site. Moreover, functional assays reveal that IND6 increased the eNOS-dependent production of NO and elicited a concentration-dependent vasodilation of endothelium-intact rat aorta due to AMPK and eNOS activation, demonstrating a functional activation of the AMPK–eNOS–NO endothelial pathway. This kinase inhibition profile, combined with the paradoxical AMPK activation in cells and arteries, suggests that these new chemical entities may constitute a valuable starting point for the development of new AMPK modulators with therapeutic potential for the treatment of vascular complications associated with obesity.
Ultrafast plasmonic photoemission in the single-cycle and few-cycle regimes
Authors: Kiss G. Zs , Földi P. , Dombi P.
Published: March 2022

Due to the highly increased interest in the development of state-of-the-art applications of photoemission in ultrafast electron microscopy, development of photocathodes and many more applications, a correct theoretical understanding of the underlying phenomena is needed. Within the framework of the single active electron approximation the most accurate results can be obtained by the direct solution of the time-dependent Schrödinger equation (TDSE). In this work, after a brief presentation of a numerically improved version of a mixed 1D-TDSE method, we investigated the characteristics of electron spectra obtained from the surface of metal nanoparticles irradiated with ultrashort laser pulses. During our investigation different decay lengths of the plasmonic-enhanced incident field in the vicinity of the metal were considered. Using the simulated spectra we managed to identify the behavior of the cutoff energy as a function of decay length in the strong-field, multiphoton and transition regimes.
Natural language analyzed with AI-based transformers predict traditional subjective well-being measures approaching the theoretical upper limits in accuracy
Authors: Kjell Oscar N. E. , Sikström Sverker , Kjell Katarina , Schwartz H. Andrew
Published: March 2022

We show that using a recent break-through in artificial intelligence –transformers–, psychological assessments from text-responses can approach theoretical upper limits in accuracy, converging with standard psychological rating scales. Text-responses use people's primary form of communication –natural language– and have been suggested as a more ecologically-valid response format than closed-ended rating scales that dominate social science. However, previous language analysis techniques left a gap between how accurately they converged with standard rating scales and how well ratings scales converge with themselves – a theoretical upper-limit in accuracy. Most recently, AI-based language analysis has gone through a transformation as nearly all of its applications, from Web search to personalized assistants (e.g., Alexa and Siri), have shown unprecedented improvement by using transformers. We evaluate transformers for estimating psychological well-being from questionnaire text- and descriptive word-responses, and find accuracies converging with rating scales that approach the theoretical upper limits (Pearson r = 0.85, p < 0.001, N = 608; in line with most metrics of rating scale reliability). These findings suggest an avenue for modernizing the ubiquitous questionnaire and ultimately opening doors to a greater understanding of the human condition.
Causal biological network models for reactive astrogliosis: a systems approach to neuroinflammation
Authors: Barkhuizen Melinda , Renggli Kasper , Gubian Sylvain , Peitsch Manuel C. , Mathis Carole , Talikka Marja
Published: March 2022

Astrocytes play a central role in the neuroimmune response by responding to CNS pathologies with diverse molecular and morphological changes during the process of reactive astrogliosis. Here, we used a computational biological network model and mathematical algorithms that allow the interpretation of high-throughput transcriptomic datasets in the context of known biology to study reactive astrogliosis. We gathered available mechanistic information from the literature into a comprehensive causal biological network (CBN) model of astrocyte reactivity. The CBN model was built in the Biological Expression Language, which is both human-readable and computable. We characterized the CBN with a network analysis of highly connected nodes and demonstrated that the CBN captures relevant astrocyte biology. Subsequently, we used the CBN and transcriptomic data to identify key molecular pathways driving the astrocyte phenotype in four CNS pathologies: samples from mouse models of lipopolysaccharide-induced endotoxemia, Alzheimer’s disease, and amyotrophic lateral sclerosis; and samples from multiple sclerosis patients. The astrocyte CBN provides a new tool to identify causal mechanisms and quantify astrogliosis based on transcriptomic data.
Small object detection method with shallow feature fusion network for chip surface defect detection
Authors: Huang Haixin , Tang Xueduo , Wen Feng , Jin Xin
Published: March 2022

The development of intelligent manufacturing often focuses on production flexibility, customization and quality control, which are crucial for chip manufacturing. Specifically, defect detection and classification are important for manufacturing processes in the semiconductor and electronics industries. The intelligent detection methods of chip defects are still challenge and have always been a particular concern of chip processing manufactures in an automated industrial production line. YOLOv4 method has been widely used for object detection due to its accuracy and speed. However, there are still difficulties and challenges in the detection for small targets, especially defects on chip surface. This study proposed a small object detection method based on YOLOv4 for small object in order to improve the performance of detection. It includes expanding feature fusion of shallow features; using k-means++ clustering to optimize the number and size of anchor box; and removing redundant YOLO head network branches to increase detection efficiency. The results of experiments reflect that SO-YOLO is superior to the original YOLOv4, YOLOv5s, and YOLOv5l models in terms of the number of parameters, classification and detection accuracy.
Multiscale heterogeneous optimal lockdown control for COVID-19 using geographic information
Authors: Neary Cyrus , Cubuktepe Murat , Lauffer Niklas , Jin Xueting , Phillips Alexander J. , Xu Zhe , Tong Daoqin , Topcu Ufuk
Published: March 2022

We study the problem of synthesizing lockdown policies—schedules of maximum capacities for different types of activity sites—to minimize the number of deceased individuals due to a pandemic within a given metropolitan statistical area (MSA) while controlling the severity of the imposed lockdown. To synthesize and evaluate lockdown policies, we develop a multiscale susceptible, infected, recovered, and deceased model that partitions a given MSA into geographic subregions, and that incorporates data on the behaviors of the populations of these subregions. This modeling approach allows for the analysis of heterogeneous lockdown policies that vary across the different types of activity sites within each subregion of the MSA. We formulate the synthesis of optimal lockdown policies as a nonconvex optimization problem and we develop an iterative algorithm that addresses this nonconvexity through sequential convex programming. We empirically demonstrate the effectiveness of the developed approach by applying it to six of the largest MSAs in the United States. The developed heterogeneous lockdown policies not only reduce the number of deceased individuals by up to 45 percent over a 100 day period in comparison with three baseline lockdown policies that are less heterogeneous, but they also impose lockdowns that are less severe.
Global gene expression profiling under nitrogen stress identifies key genes involved in nitrogen stress adaptation in maize (Zea mays L.)
Authors: Singh Prabha , Kumar Krishan , Jha Abhishek Kumar , Yadava Pranjal , Pal Madan , Rakshit Sujay , Singh Ishwar
Published: March 2022

Maize is a heavy consumer of fertilizer nitrogen (N) which not only results in the high cost of cultivation but may also lead to environmental pollution. Therefore, there is a need to develop N-use efficient genotypes, a prerequisite for which is a greater understanding of N-deficiency stress adaptation. In this study, comparative transcriptome analysis was performed using leaf and root tissues from contrasting inbred lines, viz., DMI 56 (tolerant to N stress) and DMI 81 (susceptible to N stress) to delineate the differentially expressed genes (DEGs) under low-N stress. The contrasting lines were grown hydroponically in modified Hoagland solution having either sufficient- or deficient-N, followed by high-throughput RNA-sequencing. A total of 8 sequencing libraries were prepared and 88–97% of the sequenced raw reads were mapped to the reference B73 maize genome. Genes with a p value ≤ 0.05 and fold change of ≥ 2.0 or ≤ − 2 were considered as DEGs in various combinations performed between susceptible and tolerant genotypes. DEGs were further classified into different functional categories and pathways according to their putative functions. Gene Ontology based annotation of these DEGs identified three different functional categories: biological processes, molecular function, and cellular component. The KEGG and Mapman based analysis revealed that most of the DEGs fall into various metabolic pathways, biosynthesis of secondary metabolites, signal transduction, amino acid metabolism, N-assimilation and metabolism, and starch metabolism. Some of the key genes involved in N uptake (high-affinity nitrate transporter 2.2 and 2.5), N assimilation and metabolism (glutamine synthetase, asparagine synthetase), redox homeostasis (SOD, POX), and transcription factors (MYB36, AP2-EREBP) were found to be highly expressed in the tolerant genotype compared to susceptible one. The candidate genes identified in the present study might be playing a pivotal role in low-N stress adaptation in maize and hence could be useful in augmenting further research on N metabolism and development of N-deficiency tolerant maize cultivars.
Value priorities and value conflicts in patients with mental disorders compared to a general population sample
Authors: Arens Elisabeth A. , Christoffel Muriel , Stangier Ulrich
Published: March 2022

Personal values are considered as guiding principles for humans’ attitudes and behavior, what makes them an essential component of mental health. Although these notions are widely recognized, investigations in clinical samples examining the link between values and mental health are lacking. We assessed n = 209 patients with affective disorders, neurotic disorders, reaction to severe stress, and adjustment disorders and personality disorders and compared them to a stratified random sample (n = 209) drawn from the European Social Survey. Personal values were assessed using the Portraits Value Questionnaire. Severity of psychopathology was assessed using the Beck Depression Inventory and the Brief Symptom Inventory. Clinical participants showed a higher preference for the values power, achievement and tradition/conformity and a lower preference for hedonism compared to controls. Patients exhibited more incompatible value patterns than controls. Across diagnostic groups, patients with neurotic disorders reported incompatible values most frequently. Value priorities and value conflicts may have the potential to contribute to a better understanding of current and future actions and experiences in patients with mental disorders.
Modeling material transport regulation and traffic jam in neurons using PDE-constrained optimization
Authors: Li Angran , Zhang Yongjie Jessica
Published: March 2022

The intracellular transport process plays an important role in delivering essential materials throughout branched geometries of neurons for their survival and function. Many neurodegenerative diseases have been associated with the disruption of transport. Therefore, it is essential to study how neurons control the transport process to localize materials to necessary locations. Here, we develop a novel optimization model to simulate the traffic regulation mechanism of material transport in complex geometries of neurons. The transport is controlled to avoid traffic jam of materials by minimizing a pre-defined objective function. The optimization subjects to a set of partial differential equation (PDE) constraints that describe the material transport process based on a macroscopic molecular-motor-assisted transport model of intracellular particles. The proposed PDE-constrained optimization model is solved in complex tree structures by using isogeometric analysis (IGA). Different simulation parameters are used to introduce traffic jams and study how neurons handle the transport issue. Specifically, we successfully model and explain the traffic jam caused by reduced number of microtubules (MTs) and MT swirls. In summary, our model effectively simulates the material transport process in healthy neurons and also explains the formation of a traffic jam in abnormal neurons. Our results demonstrate that both geometry and MT structure play important roles in achieving an optimal transport process in neuron.
New discovery on the nematode activity of aureothin and alloaureothin isolated from endophytic bacteria Streptomyces sp. AE170020
Authors: Kang Min-Kyoung , Kim Jong-Hoon , Liu Min-Jiao , Jin Chun-Zhi , Park Dong-Jin , Kim Junheon , Sung Bong-Hyun , Kim Chang-Jin , Son Kwang-Hee
Published: March 2022

Endophytic bacteria, a rich source of bioactive secondary metabolites, are ideal candidates for environmentally benign agents. In this study, an endophytic strain, Streptomyces sp. AE170020, was isolated and selected for the purification of nematicidal substances based on its high nematicidal activity. Two highly active components, aureothin and alloaureothin, were identified, and their chemical structures were determined using spectroscopic analysis. Both compounds suppressed the growth, reproduction, and behavior of Bursaphelenchus xylophilus. In in vivo experiments, the extracts of strain Streptomyces sp. AE170020 effectively suppressed the development of pine wilt disease in 4-year-old plants of Pinus densiflora. The potency of secondary metabolites isolated from endophytic strains suggests applications in controlling Bursaphelenchus xylophilus and opens an avenue for further research on exploring bioactive substances against the pine wood nematode.
Cost-effective wideband dielectric planar lens antenna for millimeter wave applications
Authors: Poyanco José-Manuel , Pizarro Francisco , Rajo-Iglesias Eva
Published: March 2022

This article presents a fully 3D-printed dielectric planar lens operating in the entire Ka-band manufactured using additive manufacturing and a relatively low-cost 3D-printer. The lens consists of ten concentric rings implemented using low-loss ABS filaments with high permittivity values. By varying the infill percentages of them the required refractive indexes of each section are achieved. An additional 3D-printed matching layer, using the same manufacturing and design method was included in the lens, to reduce reflections. Simulation and measurement results show a very good agreement, which confirms the possibility of manufacturing a cost-effective broadband and planar lens solution operating in millimeter wave bands, where Low Earth Orbit Satellites (LEO) networks, future mobile communication systems (5G, 6G) and radar systems operate.