bluuebunny/crossref_metadata_2025 huggingface dataset:
Key factors determining biochar sorption capacity for metal contaminants: a literature synthesis
Authors: Thomas Evert , Borchard Nils , Sarmiento Christian , Atkinson Rachel , Ladd Brenton
Published: June 2020

The sorption capacity and affinity of biochar for metals are both important attributes that determine biochar’s suitability as a soil amendment for contaminant mitigation, yet few analyses have considered both characteristics simultaneously. We present a systematic review of literature published between 2010 and 2018 to test the hypothesis that sorption capacity and affinity are affected by biochar properties, attributes of the metal contaminant, and experimental conditions, in that order. We used random forest (RF) and multi-objective optimization to analyze data of 559 individual Langmuir adsorption isotherms extracted from 133 studies covering the sorption capacity (Cmax) and affinity (KL) of biochar for 17 different metals, elaborated from six different feedstock classes, three different types of feedstock pretreatment, and five types of post-pyrolysis treatment. Highest sorption values were obtained for Pb(II), Cr(IV), and Cd(II). The feedstock used was the key determinant influencing biochar’s capacity and affinity to sorb metal contaminants (first and fourth most important variable in RF models for Cmax and KL, respectively) with best results obtained for biochar elaborated from nutrient-dense feedstocks (animal biowaste, sludge, and manure). Biochars that had both high sorption capacity and affinity were the result of a longer duration of pyrolysis; they had lower C and higher N and O content, as well as lower C/N and higher O/C and H/C ratios, higher pore volumes and higher pH. Applying some form of pretreatment was better than none, whereas chemical modification was the best of the post-treatment methods analyzed. This review demonstrates clearly that multiple parameters during the preparation process influence the effectiveness of biochar to immobilize metal contaminants. Future research that focuses on mechanisms and the underlying factors for the correlations observed should allow the development of biochar formulations that are even more effective at immobilizing metal contaminants in soils and sediments.
Dynamical invariants of monomial correspondences
Authors: DANG NGUYEN-BAC , RAMADAS ROHINI
Published: June 2020

We focus on various dynamical invariants associated to monomial correspondences on toric varieties, using algebraic and arithmetic geometry. We find a formula for their dynamical degrees, relate the exponential growth of the degree sequences to a strict log-concavity condition on the dynamical degrees and compute the asymptotic rate of the growth of heights of points of such correspondences.
No Way Back – Reflections on the Future of the African Photographic Archive
Authors: Schneider Jürg , Weinberg Paul
Published: June 2020

The article examines from a global perspective the phenomenon of digital photographic archiving and questions its impact on African archives both on the continent and outside it. The authors deal with the multi-layered consequences of information technologies for African photographic archives, asking to what degree they have connected Africa to the world. They consider too how much access they have given Africans to materials that were previously either unknown to them, or beyond their reach. Finally, the article explores how much opportunity digitization offers to agents of African photographic archives, empowered by technological developments.
“Curating Kisumu” and “Curating East Africa:” Academic Collaboration and Public Engagement in the Digital Age
Authors: Owino Meshack , Souther J. Mark
Published: June 2020

This essay examines the origin, permutations, potentials, challenges, and implications of two successive, collaborative public history research, teaching, and learning projects undertaken by the Department of History at Cleveland State University, Cleveland, Ohio, and the Department of History and Archeology at Maseno University, Kisumu, Kenya between 2014 and 2018. The two projects explored how opportunities created by the mobile revolution in Africa could be leveraged to generate new ways of acquiring historical information and knowledge between students and faculty in universities separated by enormous distances and by disparate social, economic, and political experiences. Specifically, the projects examined how the cellphone revolution could reshape the production and dissemination of knowledge about important sites, places, events, and people in modern Africa. The essay examines the conception and permutations of the two projects; identifies and explores their potentials and challenges; and proffers thoughts and suggestions that may guide similar future endeavors.
Prospective monitoring of carbapenem use and pseudomonal resistance across pediatric institutions
Authors: Miyairi Isao , Shoji Kensuke , Kinoshita Noriko , Saitoh Junpei , Sugahara Yoshie , Watanabe Yasushi , Komura Makoto , Kasai Masashi , Horikoshi Yuho , Shinjoh Masayoshi , Igarashi Takashi
Published: June 2020

Objective:

To determine whether carbapenem consumption andPseudomonas aeruginosaresistance rates can be used as benchmarks to compare and improve antimicrobial stewardship programs across multiple pediatric hospitals.

Design:

A prospective study.

Setting and participants:

Healthcare institutions in Japan with >100 pediatric beds.

Methods:

An annual survey of the total days of therapy (DOT) per 1,000 patient days for carbapenem antibiotics (meropenem, imipenem-cilastatin, panipenem-betamipron, doripenem) and susceptibility rates ofPseudomonas aeruginosato meropenem and imipenem-cilastatin from each institution was conducted over a 7-year period. Data were reported to the administration, as well as to the infection control team, of each institution annually.

Results:

Data were obtained from 32 facilities. The median total carbapenem DOT per 1,000 patient days was 16.6 and varied widely, with a range of 2.7 to 59.0. The median susceptibility to meropenem was 86.6%, ranging from 78.6% to 96.6%. We detected an inverse correlation between total carbapenem DOT versus susceptibility (r= – 0.36;P< .01). Over the 7-year period, the DOT per 1,000 patient days of carbapenem decreased by 27% from a median of 16.0 to 11.7 (P< .01). We also observed an improvement in susceptibility to meropenem from a median of 87% to 89.7% (P= .01) and to imipenem-cilastatin from 79% to 85% (P< .01). The decreases in the use of carbapenem were greater in institutions with antimicrobial stewardship programs led by pediatric infectious disease specialists.

Conclusions:

Antimicrobial use and resistance, targeting carbapenems andP. aeruginosa, respectively, can serve as benchmarks that can be utilized to promote antimicrobial stewardship across pediatric healthcare institutions.
DATING ADOPTION AND INTENSIFICATION OF FOOD-CROPS: INSIGHTS FROM 4MSR (BINJOR), AN INDUS (HARAPPAN) SITE IN NORTHWESTERN INDIA
Authors: Sharma Shalini , Manjul Sanjay Kumar , Manjul Arvin , Pande Puran Chand , Pokharia Anil K
Published: June 2020

Here we present direct dates of food grains and insights into agricultural strategies adopted by Harappans from a newly excavated Indus site 4MSR (Binjor) in northwestern India. The site revealed Early and Mature Harappan phases delimited by a Transitional phase based on ceramics and archaeological artifacts. The macro-botanical remains revealed that the site was occupied by an agricultural society during the Early phase (~2900−2600 BCE), whereas diversification of the economy including more craft specialization, along with an agricultural advancement was witnessed during the Mature phase (~2500−1800 BCE). The advent of summer crops during the Transitional phase (~2600−2500 BCE) indicates climate amelioration attributed to inception of strong Indian Summer Monsoon (ISM). By the end of Mature phase, millet was recorded due to a change in climatic (relatively lower moisture) conditions or drying of the river channel, which forced the settlers to shift the cropping (agricultural) strategy in the region. Plausibly, this unavailability of water during the end of Mature phase led the settlers to abandon the site in order to migrate somewhere else. The subsistence pattern indicates continuity and change in temporal domain likely owing to changing climatic/environmental conditions, resources and knowledge gained by exchange/trade of cultures over a time period between ~2900 BCE to 1800 BCE.
“The Low Principles of Jurisprudence”: Legal Indeterminacy in Edmund Burke's Impeachment of Warren Hastings
Authors: Goodman Rob
Published: June 2020

Edmund Burke's impeachment of Warren Hastings for his conduct as governor-general in India represented the era's most serious internal challenge to British imperialism. But the impeachment's legal and institutional implications have been neglected. The central points of contention were the nature of impeachment in Britain and the nature of law in India. Burke insisted that impeachment must override the “low” and “mean” standards of the common law, yet he celebrated India for its dense judicial institutions. Hastings took the opposite position, demanding that the impeachment adhere strictly to the common law, yet defending his conduct in India by appeal to its political expediency, rather than its lawfulness. Each found himself in a “rhetorical contradiction,” alternately arguing in praise of, and in critique of, legal reasoning and procedures. While Hastings attempted to surmount the contradiction through the discourse of realism, Burke turned to the discourse of natural law—a language of lawfulness without legalism.
ALGEBRAIC RELIABILITY OF MULTI-STATE k-OUT-OF-n SYSTEMS
Authors: Pascual-Ortigosa Patricia , Sáenz-de-Cabezón Eduardo , Wynn Henry P.
Published: June 2020

In this paper, we review different definitions that multi-state k-out-of-n systems have received along the literature and study them in a unified way using the algebra of monomial ideals. We thus obtain formulas and algorithms to compute their reliability and bounds for it. We provide formulas and computer experiments for simple and generalized multi-state k-out-of-n systems and for binary k-out-of-n systems with multi-state components.
Scoping review of Paleolithic dietary patterns: a definition proposal
Authors: de la O Víctor , Zazpe Itziar , Martínez J. Alfredo , Santiago Susana , Carlos Silvia , Zulet M. Ángeles , Ruiz-Canela Miguel
Published: June 2020

The Paleolithic diet (PaleoDiet) is an allegedly healthy dietary pattern inspired by the consumption of wild foods and animals assumed to be consumed in the Paleolithic era. Despite gaining popularity in the media, different operational definitions of this Paleolithic nutritional intake have been used in research. Our hypothesis is that specific components used to define the PaleoDiet may modulate the association of this diet with several health outcomes. We comprehensively reviewed currently applied PaleoDiet scores and suggested a new score based on the food composition of current PaleoDiet definitions and the theoretical food content of a staple dietary pattern in the Paleolithic age. In a PubMed search up to December 2019, fourteen different PaleoDiet definitions were found. We observed some common components of the PaleoDiet among these definitions although we also found high heterogeneity in the list of specific foods that should be encouraged or banned within the PaleoDiet. Most studies suggest that the PaleoDiet may have beneficial effects in the prevention of cardiometabolic diseases (type 2 diabetes, overweight/obesity, CVD and hyperlipidaemias) but the level of evidence is still weak because of the limited number of studies with a large sample size, hard outcomes instead of surrogate outcomes and long-term follow-up. Finally, we propose a new PaleoDiet score composed of eleven food items, based on a high consumption of fruits, nuts, vegetables, fish, eggs and unprocessed meats (lean meats); and a minimum content of dairy products, grains and cereals, and legumes and practical absence of processed (or ultra-processed) foods or culinary ingredients.
Tainted Largess: A Moral Framework For Medical School Donations
Authors: SANKY CHARLES , APPEL JACOB M.
Published: June 2020

Rather than being a neutral phenomenon, the authors propose that medical school donations should be viewed as a social good for advancing education and improving healthcare. Seen in this light, they aim to offer a framework for analysis that will be useful to medical institutions and their stakeholders in addressing proposed donations from contentious or divisive sources, and in managing those donations that subsequently appear controversial.
Avoiding Gender Exploitation and Ethics Dumping in Research with Women
Authors: COOK JULIE
Published: June 2020

There is a long history of women being underrepresented in biomedical and health research. Specific women’s health needs have been, and in some cases still are, comparatively neglected areas of study. Concerns about the health and social impacts of such bias and exclusion have resulted in inclusion policies from governments, research funders, and the scientific establishment since the 1990s. Contemporary understandings of foregrounding sex and gender issues within biomedical research range from women’s rights to inclusion, to links between human rights, women’s health and sustainable development, and the increasing scientific and funding expectation for studies to consider the sex (biological) and gender (cultural) implications of research design, results and impact. However, there are also exploitation issues to consider when foregrounding the inclusion of women as research participants, especially for research ethics committees and institutional review boards. A hidden risk is that exploitative research designs and practices may be missed, particularly by reviewers who may not have a nuanced understanding of gender-based harm. Utilizing contemporary case studies of ethics dumping, this paper highlights some of the concerns, and makes recommendations for IRBs/research ethics reviewers to help ensure that essential research is undertaken to the highest ethical standards.
Bridging Secondary and Higher Education. The Importance of Self-regulated Learning
Authors: Vosniadou Stella
Published: June 2020

It is proposed that the transition from secondary to higher education can be facilitated by improving secondary school students’ capabilities for independent, self-directed, and self-regulated learning (SRL). University learning places high demands on students for complex and independent learning, namely learning that requires the ability to plan, monitor and evaluate one’s work and to control one’s motivation and emotion. A major stream of educational research has shown the beneficial impact of self-regulated learning on student motivation and has concluded that self-regulation is a significant source of achievement differences among students. However, many secondary school students lack the skills of an independent and self-regulated learner when they enter higher education, something that contributes to considerable student attrition during the first year of university study. In this article I argue that more attention should be paid to the promotion of self-regulated learning in secondary schools. This can be achieved by helping teachers understand how to enrich students’ knowledge about learning and strategies to manage it. Some exemplary practices developed at secondary schools are discussed as a means of providing examples of effective learning environments for SRL.
‘Removing the Barriers’: Mary Midgley on Concern for Animals
Authors: Cooper David E.
Published: June 2020

This paper focuses on Mary Midgley's influential discussions, over more than thirty years, of the relationship between human beings and animals, in particular on her concern to ‘remove the barriers’ that stand in the way of proper understanding and treatment of animals. These barriers, she demonstrates, have been erected by animal science, epistemology and mainstream moral philosophy alike. In each case, she argues, our attitudes to animals are warped by approaches that are at once excessively abstract, over-theoretical and guilty of a collective hubris on the part of humankind. In keeping with Midgley's own position, it is argued in this paper that, to remove these barriers, what is required is not yet another theory of how and why animals matter, but attention to actual engagements with animals and to the moral failings or vices that distort people's relationships with them.
Distribution characteristics of circulating homocysteine and folate and related factors in agriculture, stock-raising and urban populations: a cross-sectional survey
Authors: Pan Fengyu , Heizhati Mulalibieke , Wang Lin , Zhou Ling , Hong Jing , Zhang Delian , Chang Guijuan , Luo Qin , Sun Le , Yue Na , Li Nanfang
Published: June 2020

Objective:

To investigate homocysteine (Hcy) and folate levels, prevalence of hyperhomocysteinaemia (HHcy) and folate deficiency, which are affected by lifestyles in urban, agricultural and stock-raising populations.

Design:

This is a cross-sectional study.

Setting:

Urban, agricultural and stock-raising regions in Emin, China.

Participants:

Totally 1926 subjects – 885 (45·9 %) from urban, 861 (44·7 %) from agricultural and 180 (9·4 %) from stock-raising regions – were obtained using multistage stratified random sampling. Inclusion criteria encompassed inhabitants aged ≥15 years who resided at the current address for ≥6 months and agreed to participate in the study. Surveys on health behaviour questionnaires and physical examinations were conducted and blood samples collected.

Results:

The folate level of subjects from the stock-raising region was the lowest, followed by those from the agricultural region, and the highest in those from the urban region (3·48 v. 6·50 v. 7·12 ng/ml, P < 0·001), whereas mean Hcy showed no significant difference across regions. The OR for HHcy in stock-raising regions was 1·90 (95 % CI 1·11, 3·27) compared with the urban region after adjusting for all possible covariates. The OR for folate deficiency in stock-raising and agriculture regions was 11·51 (95 % CI 7·09, 18·67) and 1·91 (95 % CI 1·30, 2·82), respectively, compared with the urban region after adjusting for all possible covariates.

Conclusions:

HHcy and folate deficiency are highly prevalent in stock-raisers, which is of important reference for HHcy control in Xinjiang, with a possibility of extension to others with approximate lifestyles.
Factors associated with the onset of major depressive disorder in adults with type 2 diabetes living in 12 different countries: results from the INTERPRET-DD prospective study
Authors: Lloyd C. E. , Sartorius N. , Ahmed H. U. , Alvarez A. , Bahendeka S. , Bobrov A. E. , Burti L. , Chaturvedi S. K. , Gaebel W. , de Girolamo G. , Gondek T. M. , Guinzbourg M. , Heinze M. G. , Khan A. , Kiejna A. , Kokoszka A. , Kamala T. , Lalic N. M. , Lecic-Tosevski D. , Mannucci E. , Mankovsky B. , Müssig K. , Mutiso V. , Ndetei D. , Nouwen A. , Rabbani G. , Srikanta S. S. , Starostina E. G. , Shevchuk M. , Taj R. , Valentini U. , van Dam K. , Vukovic O. , Wölwer W.
Published: June 2020

Aims

To examine the factors that are associated with changes in depression in people with type 2 diabetes living in 12 different countries.

Methods

People with type 2 diabetes treated in out-patient settings aged 18–65 years underwent a psychiatric assessment to diagnose major depressive disorder (MDD) at baseline and follow-up. At both time points, participants completed the Patient Health Questionnaire (PHQ-9), the WHO five-item Well-being scale (WHO-5) and the Problem Areas in Diabetes (PAID) scale which measures diabetes-related distress. A composite stress score (CSS) (the occurrence of stressful life events and their reported degree of ‘upset’) between baseline and follow-up was calculated. Demographic data and medical record information were collected. Separate regression analyses were conducted with MDD and PHQ-9 scores as the dependent variables.

Results

In total, there were 7.4% (120) incident cases of MDD with 81.5% (1317) continuing to remain free of a diagnosis of MDD. Univariate analyses demonstrated that those with MDD were more likely to be female, less likely to be physically active, more likely to have diabetes complications at baseline and have higher CSS. Mean scores for the WHO-5, PAID and PHQ-9 were poorer in those with incident MDD compared with those who had never had a diagnosis of MDD. Regression analyses demonstrated that higher PHQ-9, lower WHO-5 scores and greater CSS were significant predictors of incident MDD. Significant predictors of PHQ-9 were baseline PHQ-9 score, WHO-5, PAID and CSS.

Conclusion

This study demonstrates the importance of psychosocial factors in addition to physiological variables in the development of depressive symptoms and incident MDD in people with type 2 diabetes. Stressful life events, depressive symptoms and diabetes-related distress all play a significant role which has implications for practice. A more holistic approach to care, which recognises the interplay of these psychosocial factors, may help to mitigate their impact on diabetes self-management as well as MDD, thus early screening and treatment for symptoms is recommended.
The Genetics of Reading and Language
Authors: Luciano Michelle , Bates Timothy C.
Published: June 2020

Recounts how our collaboration with Nick Martin was shaped over two decades, leading to the first studies of predictions from the ‘Dual Route Cascaded’ computational model of reading in twins, and extending into the molecular work, first linkage, fine mapping of genes identified in pedigree studies, into now the genomewide association study era and the first polygenic risk scores for reading and their potential in early clarifying causality and validating interventions, as well as for future global collaborations in improving these predictors and identifying causal variants. We highlight Nick’s warm, future-focused optimism, support and inclusive approach without which none of this would have been possible. The circle of Nick asking, over half a century ago, ‘What genes do you think make some kids get better grades?’ has built a diverse scientific legacy involving thousands of papers and collaborations. The (heritable) traits of curiosity, boldness, warmth, interest in societally important questions, openness to new methods, ambition and collaborative skill to bring into being the infrastructure and samples needed for this research are rare, and we are grateful.
The relationships between systemic cytokine profiles and inflammatory markers in colorectal cancer and the prognostic significance of these parameters
Authors: Park Ji Won , Chang Hee Jin , Yeo Hyun Yang , Han Nayoung , Kim Byung Chang , Kong Sun-Young , Kim Jeongseon , Oh Jae Hwan
Published: June 2020

Background

Immunomodulatory cytokines and systemic inflammatory markers are important during cancer development and progression. This study investigated the association and prognostic impact of systemic cytokine profiles and inflammatory markers in colorectal cancer (CRC).

Methods

Interleukin (IL)-1β, IL-6, IL-8, IL-9, IL-10, tumour necrosis factor (TNF)-α and vascular endothelial growth factor (VEGF) serum levels were measured using multiplex bead assays in CRC patients. Data on systemic inflammatory markers, such as the modified Glasgow prognostic score (mGPS), the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), prognostic nutritional index (PNI) and fibrinogen, were collected. Survival analysis was performed to identify factors associated with progression-free survival (PFS) and overall survival (OS).

Results

There were moderate-to-strong correlations within serum cytokines, as well as within systemic inflammatory markers, whereas the associations between serum cytokines and systemic inflammatory markers were generally weak. IL-8 and the LMR were independent significant prognostic factors for PFS and OS. The low IL-8 and high LMR group had the best survival (both PFS and OS) of all groups.

Conclusions

Systemic cytokine profiles and inflammatory markers have relatively weak intergroup correlations. A composite classification of systemic cytokine profiles and inflammatory markers has an enhanced prognostic value in CRC.
FMRP(1–297)-tat restores ion channel and synaptic function in a model of Fragile X syndrome
Authors: Zhan Xiaoqin , Asmara Hadhimulya , Cheng Ning , Sahu Giriraj , Sanchez Eduardo , Zhang Fang-Xiong , Zamponi Gerald W. , Rho Jong M. , Turner Ray W.
Published: June 2020

Fragile X Syndrome results from a loss of Fragile X Mental Retardation Protein (FMRP). We now show that FMRP is a member of a Cav3-Kv4 ion channel complex that is known to regulate A-type potassium current in cerebellar granule cells to produce mossy fiber LTP. Mossy fiber LTP is absent in Fmr1 knockout (KO) mice but is restored by FMRP(1-297)-tat peptide. This peptide further rapidly permeates the blood-brain barrier to enter cells across the cerebellar-cortical axis that restores the balance of protein translation for at least 24 h and transiently reduces elevated levels of activity of adult Fmr1 KO mice in the Open Field Test. These data reveal that FMRP(1-297)-tat can improve function from the levels of protein translation to synaptic efficacy and behaviour in a model of Fragile X syndrome, identifying a potential therapeutic strategy for this genetic disorder.
The tumour microenvironment shapes dendritic cell plasticity in a human organotypic melanoma culture
Authors: Di Blasio S. , van Wigcheren G. F. , Becker A. , van Duffelen A. , Gorris M. , Verrijp K. , Stefanini I. , Bakker G. J. , Bloemendal M. , Halilovic A. , Vasaturo A. , Bakdash G. , Hato S. V. , de Wilt J. H. W. , Schalkwijk J. , de Vries I. J. M. , Textor J. C. , van den Bogaard E. H. , Tazzari M. , Figdor C. G.
Published: June 2020

The tumour microenvironment (TME) forms a major obstacle in effective cancer treatment and for clinical success of immunotherapy. Conventional co-cultures have shed light onto multiple aspects of cancer immunobiology, but they are limited by the lack of physiological complexity. We develop a human organotypic skin melanoma culture (OMC) that allows real-time study of host-malignant cell interactions within a multicellular tissue architecture. By co-culturing decellularized dermis with keratinocytes, fibroblasts and immune cells in the presence of melanoma cells, we generate a reconstructed TME that closely resembles tumour growth as observed in human lesions and supports cell survival and function. We demonstrate that the OMC is suitable and outperforms conventional 2D co-cultures for the study of TME-imprinting mechanisms. Within the OMC, we observe the tumour-driven conversion of cDC2s into CD14+ DCs, characterized by an immunosuppressive phenotype. The OMC provides a valuable approach to study how a TME affects the immune system.
Development of an exon skipping therapy for X-linked Alport syndrome with truncating variants in COL4A5
Authors: Yamamura Tomohiko , Horinouchi Tomoko , Adachi Tomomi , Terakawa Maki , Takaoka Yutaka , Omachi Kohei , Takasato Minoru , Takaishi Kiyosumi , Shoji Takao , Onishi Yoshiyuki , Kanazawa Yoshito , Koizumi Makoto , Tomono Yasuko , Sugano Aki , Shono Akemi , Minamikawa Shogo , Nagano China , Sakakibara Nana , Ishiko Shinya , Aoto Yuya , Kamura Misato , Harita Yutaka , Miura Kenichiro , Kanda Shoichiro , Morisada Naoya , Rossanti Rini , Ye Ming Juan , Nozu Yoshimi , Matsuo Masafumi , Kai Hirofumi , Iijima Kazumoto , Nozu Kandai
Published: June 2020

Currently, there are no treatments for Alport syndrome, which is the second most commonly inherited kidney disease. Here we report the development of an exon-skipping therapy using an antisense-oligonucleotide (ASO) for severe male X-linked Alport syndrome (XLAS). We targeted truncating variants in exon 21 of the COL4A5 gene and conducted a type IV collagen α3/α4/α5 chain triple helix formation assay, and in vitro and in vivo treatment efficacy evaluation. We show that exon skipping enabled trimer formation, leading to remarkable clinical and pathological improvements including expression of the α5 chain on glomerular and the tubular basement membrane. In addition, the survival period was clearly prolonged in the ASO treated mice group. This data suggests that exon skipping may represent a promising therapeutic approach for treating severe male XLAS cases.
Anion order in oxysulfide perovskites: origins and implications
Authors: Pilania Ghanshyam , Ghosh Ayana , Hartman Steven T. , Mishra Rohan , Stanek Christopher R. , Uberuaga Blas P.
Published: June 2020

Heteroanionic oxysulfide perovskite compounds represent an emerging class of new materials allowing for a wide range of tunability in the electronic structure that could lead to a diverse spectrum of novel and improved functionalities. Unlike cation ordered double perovskites—where the origins and design rules of various experimentally observed cation orderings are well known and understood—anion ordering in heteroanionic perovskites remains a largely uncharted territory. In this contribution, we present and discuss insights that have emerged from our first-principles-based electronic structure analysis of a prototypical anion-ordered SrHf(O0.5S0.5)3 oxysulfide chemistry, studied in all possible anion configurations allowed within a finite size supercell. We demonstrate that the preferred anion ordering is always an all-cis arrangement of anions around an HfO3S3 octahedron. As a general finding beyond the specific chemistry, the origins of this ordering tendency are traced back to a combined stabilization effect stemming from electronic, elastic, and electrostatic contributions. These qualitative notions are also quantified using state-of-the-art machine learning models. We further study the relative stability of the identified ordering as a function of A (Ca, Sr, Ba) and B (Ti, Zr, Hf) site chemistries and probe chemistry-dependent trends in the electronic structure and functionality of the material. Most remarkably, we find that the identified ground-state anion ordering breaks the inversion symmetry to create a family of oxysulfide ferroelectrics with a macroscopic polarization >30 μC/cm2, exhibiting a significant promise for electronic materials applications.
Stratification and prediction of drug synergy based on target functional similarity
Authors: Yang Mi , Jaaks Patricia , Dry Jonathan , Garnett Mathew , Menden Michael P. , Saez-Rodriguez Julio
Published: June 2020

Drug combinations can expand therapeutic options and address cancer’s resistance. However, the combinatorial space is enormous precluding its systematic exploration. Therefore, synergy prediction strategies are essential. We here present an approach to prioritise drug combinations in high-throughput screens and to stratify synergistic responses. At the core of our approach is the observation that the likelihood of synergy increases when targeting proteins with either strong functional similarity or dissimilarity. We estimate the similarity applying a multitask machine learning approach to basal gene expression and response to single drugs. We tested 7 protein target pairs (representing 29 combinations) and predicted their synergies in 33 breast cancer cell lines. In addition, we experimentally validated predicted synergy of the BRAF/insulin receptor combination (Dabrafenib/BMS-754807) in 48 colorectal cancer cell lines. We anticipate that our approaches can be used for prioritization of drug combinations in large scale screenings, and to maximize the efficacy of drugs already known to induce synergy, ultimately enabling patient stratification.
Effects of Laser-Beam Defocus on Microstructural Features of Compositionally Graded WC/Co-Alloy Composites Additively Manufactured by Multi-Beam Laser Directed Energy Deposition
Authors: Kunimine Takahiro , Miyazaki Ryusei , Yamashita Yorihiro , Funada Yoshinori
Published: June 2020

Establishing processing routes for obtaining metal-matrix composites (MMCs) with uniformly-dispersed reinforcements is one of the main subjects in additively manufactured composite materials to achieve designed microstructures and mechanical properties. Here we report on the microstructural features of compositionally graded WC/Co-alloy composites additively manufactured by multi-beam laser directed energy deposition (multi-beam LDED). For tailoring microstructures of compositionally graded WC/Co-alloy composites with uniformly-dispersed reinforcements, the combinational method: the laser-beam defocus function in the multi-beam LDED system and granulated powder was attempted. By laser defocusing in the multi-beam LDED system, composites with uniformly-dispersed WC particles in Co alloy matrix was successfully obtained due to melting of Co bond in WC-12 wt.%Co granulated particles. It was found that the laser defocusing of multi-beam lasers affects temperature increase of flying powder during the laser focusing area, resulting in change of processing mode from melt-pool mode to thermal spray mode. The preferable property gradients in the WC/Co-alloy composites could be obtained by controlling the feeding rate of the powders and laser-beam defocus. These experimental results demonstrated the effectiveness of the laser-beam-defocus function in the multi-beam LDED system as a key factor for tailoring microstructures of additively-manufactured functionally graded MMCs with uniformly-dispersed reinforcements.
Synergism between the Black Queen effect and the proteomic constraint on genome size reduction in the photosynthetic picoeukaryotes
Authors: Derilus D. , Rahman M. Z. , Pinero F. , Massey S. E.
Published: June 2020

The photosynthetic picoeukaryotes (PPEs) comprise a rare example of free-living eukaryotes that have undergone genome reduction. Here, we examine a duality in the process; the proposed driver of genome reduction (the Black Queen hypothesis, BQH), and the resultant impact of genome information loss (the Proteomic Constraint hypothesis, PCH). The BQH predicts that some metabolites may be shared in the open ocean, thus driving loss of redundant metabolic pathways in individual genomes. In contrast, the PCH predicts that as the information content of a genome is reduced, the total mutation load is also reduced, leading to loss of DNA repair genes due to the resulting reduction in selective constraint. Consistent with the BQH, we observe that biosynthetic pathways involved with soluble metabolites such as amino acids and carotenoids are preferentially lost from the PPEs, in contrast to biosynthetic pathways involved with insoluble metabolites, such as lipids, which are retained. Consistent with the PCH, a correlation between proteome size and the number of DNA repair genes, and numerous other informational categories, is observed. While elevated mutation rates resulting from the loss of DNA repair genes have been linked to reduced effective population sizes in intracellular bacteria, this remains to be established. This study shows that in microbial species with large population sizes, an underlying factor in modulating their DNA repair capacity appears to be information content.
Genome sequence and comparative analysis of reindeer (Rangifer tarandus) in northern Eurasia
Authors: Weldenegodguad Melak , Pokharel Kisun , Ming Yao , Honkatukia Mervi , Peippo Jaana , Reilas Tiina , Røed Knut H. , Kantanen Juha
Published: June 2020

Reindeer are semi-domesticated ruminants that have adapted to the challenging northern Eurasian environment characterized by long winters and marked annual fluctuations in daylight. We explored the genetic makeup behind their unique characteristics by de novo sequencing the genome of a male reindeer and conducted gene family analyses with nine other mammalian species. We performed a population genomics study of 23 additional reindeer representing both domestic and wild populations and several ecotypes from various geographic locations. We assembled 2.66 Gb (N50 scaffold of 5 Mb) of the estimated 2.92 Gb reindeer genome, comprising 27,332 genes. The results from the demographic history analysis suggested marked changes in the effective population size of reindeer during the Pleistocene period. We detected 160 reindeer-specific and expanded genes, of which zinc finger proteins (n = 42) and olfactory receptors (n = 13) were the most abundant. Comparative genome analyses revealed several genes that may have promoted the adaptation of reindeer, such as those involved in recombination and speciation (PRDM9), vitamin D metabolism (TRPV5, TRPV6), retinal development (PRDM1, OPN4B), circadian rhythm (GRIA1), immunity (CXCR1, CXCR2, CXCR4, IFNW1), tolerance to cold-triggered pain (SCN11A) and antler development (SILT2). The majority of these characteristic reindeer genes have been reported for the first time here. Moreover, our population genomics analysis suggested at least two independent reindeer domestication events with genetic lineages originating from different refugial regions after the Last Glacial Maximum. Taken together, our study has provided new insights into the domestication, evolution and adaptation of reindeer and has promoted novel genomic research of reindeer.
Zika Virus NS3 Protease Pharmacophore Anchor Model and Drug Discovery
Authors: Pathak Nikhil , Kuo Yi-Ping , Chang Teng-Yuan , Huang Chin-Ting , Hung Hui-Chen , Hsu John Tsu-An , Yu Guann-Yi , Yang Jinn-Moon
Published: June 2020

Zika virus (ZIKV) of the flaviviridae family, is the cause of emerging infections characterized by fever, Guillain-Barré syndrome (GBS) in adults and microcephaly in newborns. There exists an urgent unmet clinical need for anti-ZIKV drugs for the treatment of infected individuals. In the current work, we aimed at the promising virus drug target, ZIKV NS3 protease and constructed a Pharmacophore Anchor (PA) model for the active site. The PA model reveals a total of 12 anchors (E, H, V) mapped across the active site subpockets. We further identified five of these anchors to be critical core anchors (CEH1, CH3, CH7, CV1, CV3) conserved across flaviviral proteases. The ZIKV protease PA model was then applied in anchor-enhanced virtual screening yielding 14 potential antiviral candidates, which were tested by in vitro assays. We discovered FDA drugs Asunaprevir and Simeprevir to have potent anti-ZIKV activities with EC50 values 4.7 µM and 0.4 µM, inhibiting the viral protease with IC50 values 6.0 µM and 2.6 µM respectively. Additionally, the PA model anchors aided in the exploration of inhibitor binding mechanisms. In conclusion, our PA model serves as a promising guide map for ZIKV protease targeted drug discovery and the identified ‘previr’ FDA drugs are promising for anti-ZIKV treatments.
Saturation of radiative heat transfer due to many-body thermalization
Authors: Latella Ivan , Messina Riccardo , Biehs Svend-Age , Rubi J. Miguel , Ben-Abdallah Philippe
Published: June 2020

Radiative heat transfer between two bodies saturates at very short separation distances due to the nonlocal optical response of the materials. In this work, we show that the presence of radiative interactions with a third body or external bath can also induce a saturation of the heat transfer, even at separation distances for which the optical response of the materials is purely local. We demonstrate that this saturation mechanism is a direct consequence of a thermalization process resulting from many-body interactions in the system. This effect could have an important impact in the field of nanoscale thermal management of complex systems and in the interpretation of measured signals in thermal metrology at the nanoscale.
Drug response analysis for scaffold-free cardiac constructs fabricated using bio-3D printer
Authors: Arai Kenichi , Murata Daiki , Takao Shoko , Nakamura Anna , Itoh Manabu , Kitsuka Takahiro , Nakayama Koichi
Published: June 2020

Cardiac constructs fabricated using human induced pluripotent stem cells-derived cardiomyocytes (iPSCs-CMs) are useful for evaluating the cardiotoxicity of and cardiac response to new drugs. Previously, we fabricated scaffold-free three-dimensional (3D) tubular cardiac constructs using a bio-3D printer, which can load cardiac spheroids onto a needle array. In this study, we developed a method to measure the contractile force and to evaluate the drug response in cardiac constructs. Specifically, we measured the movement of the needle tip upon contraction of the cardiac constructs on the needle array. The contractile force and beating rate of the cardiac constructs were evaluated by analysing changes in the movement of the needle tip. To evaluate the drug response, contractile properties were measured following treatment with isoproterenol, propranolol, or blebbistatin, in which the movement of the needle tip was increased following isoproterenol treatment, but was decreased following propranolol or blebbistain, treatments. To evaluate cardiotoxicity, contraction and cell viability of the cardiac constructs were measured following doxorubicin treatment. Cell viability was found to decrease with decreasing movement of the needle tip following doxorubicin treatment. Collectively, our results show that this method can aid in evaluating the contractile force of cardiac constructs.
PLGA nanoparticles loaded with Gallic acid- a constituent of Leea indica against Acanthamoeba triangularis
Authors: Mahboob Tooba , Nawaz Muhammad , de Lourdes Pereira Maria , Tian-Chye Tan , Samudi Chandramathi , Sekaran Shamala Devi , Wiart Christophe , Nissapatorn Veeranoot
Published: June 2020

Acanthamoeba, a genus that contains at least 24 species of free-living protozoa, is ubiquitous in nature. Successful treatment of Acanthamoeba infections is always very difficult and not always effective. More effective drugs must be developed, and medicinal plants may have a pivotal part in the future of drug discovery. Our research focused on investigating the in vitro anti- acanthamoebic potential of Leea indica and its constituent gallic acid in different concentrations. Water and butanol fractions exhibited significant amoebicidal activity against trophozoites and cysts. Gallic acid (100 µg/mL) revealed 83% inhibition of trophozoites and 69% inhibition of cysts. The butanol fraction induced apoptosis in trophozoites, which was observed using tunnel assay. The cytotoxicity of the fractions and gallic acid was investigated against MRC-5 and no adverse effects were observed. Gallic acid was successfully loaded within poly (D,L-lactide-co-glycolide) (PLGA) nanoparticles with 82.86% encapsulation efficiency, while gallic acid showed 98.24% in vitro release at 48 hours. Moreover, the gallic acid encapsulated in the PLGA nanoparticles exhibited 90% inhibition against trophozoites. In addition, gallic acid encapsulated nanoparticles showed reduced cytotoxicity towards MRC-5 compared to gallic acid, which evidenced that natural product nanoencapsulation in polymeric nanoparticles could play an important role in the delivery of natural products.
Synthesis and characterization of Magnesium-Iron-Cobalt complex hydrides
Authors: Barale Jussara , Deledda Stefano , Dematteis Erika M. , Sørby Magnus H. , Baricco Marcello , Hauback Bjørn C.
Published: June 2020

The formation, structure and deuterium desorption properties of Mg2FexCo(1−x)Dy (0 ≤ x ≤ 1 and 5 ≤ y ≤ 6) complex hydrides were investigated. The synthesis was carried out by reactive ball milling, using a mixture of powders of the parent elements in D2 atmosphere. The formation of quaternary deuterides was identified from Rietveld refinements of powder X-Ray diffraction and powder neutron diffraction patterns, and from infrared attenuated total reflectance analysis. It was observed that the crystal structure of deuterides depends on the transition metal fraction. For Co-rich compositions, i.e. up to x = 0.1, hydrides have the tetragonal distorted CaF2-type structure (space group P4/nmm) of Mg2CoD5 at room temperature. For Fe-rich compositions, i.e. x ≥ 0.5, a cubic hydride is observed, with the same K2PtCl6-type structure (space group Fm$$\bar{{\bf{3}}}$$3¯m) as Mg2FeD6 and as Mg2CoD5 at high temperatures. For x = 0.3, both the cubic and the tetragonal deuterides are detected. Differential scanning calorimetry coupled with thermogravimetric and temperature programmed desorption analyses show rather similar deuterium desorption properties for all samples, without significant changes as a function of composition. Finally, hydrogen sorption experiments performed for Mg2Fe0.5Co0.5H5.5 at 30 bar of H2 and 673 K showed reversible reactions, with good kinetic for both absorption and desorption of hydrogen.
New Synthesis Route for Complex Borides; Rapid Synthesis of Thermoelectric Yttrium Aluminoboride via Liquid-Phase Assisted Reactive Spark Plasma Sintering
Authors: Son Hyoung-Won , Berthebaud David , Yubuta Kunio , Yoshikawa Akira , Shishido Toetsu , Suzuta Keiko , Mori Takao
Published: June 2020

YxAlyB14 ceramics are of high interest as high temperature thermoelectric materials with excellent p, n control. In this study, direct synthesis of dense polycrystalline YxAlyB14 (x ~0.64, 0.52 ≤ y ≤ 0.67) ceramics was successfully carried out by spark plasma sintering using commercially available precursors. YB4, AlB2 and B powders were reactively sintered with an additive AlF3 at 1773 K for 5–60 min in reduced Ar atmosphere. The sinterability was remarkably enhanced by liquid phase sintering comparing to conventional synthesis techniques. Phase composition analysis by X-ray diffraction showed that main peaks belong to YxAlyB14 with the MgAlB14 structure type and no peaks of AlF3 were detected. The thermoelectric behavior was changed from p-type to n-type with increasing Al occupancy. Power factor and ZT values measured in this study were found to be in the same range as the best values previously reported. This original synthesis process is found to be less precursor-consuming as compared to previous synthesis processes, and strikingly, less time-consuming, as the synthesis time, is shortened from 8 h to 5 min for p-type and to 1 h for n-type. The total process time is shortened from ≥3 days to ~4–5 h. This discovery opens the door for more accessible synthesis of complex borides.
Extracellular vesicles produced by NFAT3-expressing cells hinder tumor growth and metastatic dissemination
Authors: de Camargo Lívia Cardoso Bueno , Guaddachi Frédéric , Bergerat David , Ourari Nadia , Coillard Lucie , Parietti Veronique , Le Bras Morgane , Lehmann-Che Jacqueline , Jauliac Sébastien
Published: June 2020

Metastases are the main cause of cancer-induced deaths worldwide. To block tissue invasion, development of extracellular vesicles (EVs) as therapeutic carriers, appears as an exciting challenge. To this aim, we took advantage of the anti-invasive function of NFAT3 transcription factor we identified previously in breast cancer and addressed the opportunity to transfer this inhibitory function by EVs. We show here that EVs produced by poorly invasive NFAT3-expressing breast cancer cell lines are competent to block in vitro invasion of aggressive cancer cells from different origins and, in cooperation with macrophages, inhibit cell proliferation and induce apoptosis. Moreover, this inhibitory effect can be improved by overexpression of NFAT3 in the EVs-producing cells. These results were extended in a mouse breast cancer model, with clear impact of inhibitory EVs on tumor growth and metastases spreading. This work identifies EVs produced by NFAT3-expressing breast cancer cells as an anti-tumoral tool to tackle cancer development and metastases dissemination.