bluuebunny/crossref_metadata_2025 huggingface dataset:
Education Policies for Gifted Children Within a Human Rights Paradigm: a Comparative Analysis
Authors: Ninkov Ivona
Published: October 2020

Gifted students are the most important part of every society and keeping the gifted child challenged and engaged is necessary. This paper aims to offer suggestions for the appropriate education system to enlarge their knowledge and creativity, without disturbing their usual life and educational surroundings. The author uses a comparative method, focusing on different countries worldwide and comparing and interpreting the various concepts of education in those countries. Based on the United Nations regionalization, the author focuses on the countries of the Eastern European Group (Bosnia and Herzegovina, Croatia, Hungary, and Serbia) and Western European and Others Group (Austria, Germany, Netherlands, UK, Turkey, and the USA). The study finds that inclusive education as an alternative framework is potentially the best education system for gifted students. The prevailing opinion in most countries is that the concept of inclusive education primarily refers to children with special needs. This authorexplains that there is no logical obstacle to applying inclusive education to gifted students as well. Such an inclusive education system would require changing current education systems and programs and, most of all, hiring various professional staff as social workers and trained teachers who can meet the various demanding needs of gifted students in any community. The study concludes that it is necessary to improve existing policies in education to provide the inclusive education framework to gifted children and to understand that the essence is not only to agree on differences but to stimulate the individuality and diversity of the gifted at all levels; the greatest gem of each country is its educated children. Inclusion of gifted students has a positive outcome not only for the individual but also for the other students in the classroom. Gifted students stimulate the others, pushing them to reach their potential academic capabilities. Also, the unidentified students who could learn at elevated levels could benefit from this kind of education model and a high level of instruction could push them in the same way that it challenges the gifted students in the classroom.
Intercomparison of Sonde, WRF/CAMx and Satellite Sounder Profile Data for the Paso Del Norte Region
Authors: Mahmud Suhail , Karle Nakul N. , Fitzgerald Rosa M. , Lu Duanjun , Nalli Nicholas R. , Stockwell William R.
Published: October 2020

The Paso Del Norte (PdN) region comprises the city of El Paso, TX, Ciudad Juarez, Mexico, and some neighboring cities in the state of New Mexico. Developing a regional weather model for this specific region has always been challenging due to its complex terrain. To obtain more accurate weather and pollution forecasting for the PdN region, the results of the downscaled WRF (Weather Research and Forecast) model were intercompared with meteorological satellite data, with ground and radiosonde dataset. In addition, it is critical to analyze the distributions of ozone concentrations to better understand atmospheric aerosol concentrations and predict them both more accurately. Hence, in this study the ozone results of CAMx (Comprehensive Air Quality Model with Extensions) were extensively intercompared with ozonesonde data. The radiosonde/ozonesonde data were obtained throughout a campaign conducted during the summer of 2017 in the PdN region. Different meteorological variables such as temperature, pressure, relative humidity, wind speed, and ozone concentrations were used for comparison at several locations in the PdN region. The TCEQ (Texas Commission of Environment Quality) data from different CAMS (Continuous Ambient Monitoring Stations) were used for ground data intercomparison with the WRF results. The meteorological satellite sounding data were retrieved using an in-house satellite antenna receiver. The results of this research paper will not only provide better pollution forecasting capability for the PdN region but also for other regions with similar topography and terrain.
The application of a new, innovative, hybrid technology combining hardfacing and nitriding to increase the durability of forging tools
Authors: Kaszuba Marcin
Published: October 2020

The article deals with the wear of forging tools used in hot forging processes. The research presented in the work includes analysis of tool life used in a selected industrial hot die forging process. Multiple treatment variants were used to increase wear resistance, including thermo-chemical treatment (nitriding), welding methods (surfacing) and an innovative new hybrid technology combining surfacing and nitriding. First of all, the research focused on determining the impact of the phase structure of the nitrided layers used and the surfacing layer on resistance to destructive factors occurring in the analyzed process. Next, hybrid treated tools combining surfacing and nitriding were also subjected to operational tests. Each of the tools analyzed in this work was operated until it was withdrawn due to excessive wear, and then subjected to comprehensive analysis. The tests of tools after operation included: surface scanning to determine the amount of wear of the analyzed tools after work, microhardness measurement, and microscopic tests. A detailed analysis of changes in the surface layer of tools in selected areas was made using a scanning microscope. The aim of the study was to assess the effectiveness of the hybrid surface treatment process used to increase the wear resistance of the surface layer of tools and thereby improve the durability of the forged tools analyzed. The obtained research results indicate a beneficial effect of using the new technology resulting in 300% increase in the durability of the analyzed tools. The effect of improving durability confirmed by obtained results arises from the use of hybrid layers, which are more resistant to abrasive wear and to cracking due to thermo-mechanical fatigue. Moreover, the study shows that nitriding may have a beneficial influence on improving the lifetime of forging tools, under the condition that the nitrided layer has an α diffusive layer structure, without a larger amount of γ’ and ε nitride precipitates.
A Narrative Review of the Needs of Children in Foster and Kinship Care: Informing a Research Agenda
Authors: Kemmis-Riggs Jacqueline , McAloon John
Published: October 2020

As a result of maltreatment, children in care can present with a range of complex needs and challenges. In addition to direct clinical care commonly provided by paediatricians, psychiatrists, and clinical psychologists, the provision of knowledge and skills to foster and kinship carers have become modes of support common in responding to these needs and challenges. A narrative review of key systematic reviews and empirical research was conducted to assess the effectiveness of existing foster carer interventions. Results indicated a range of methodological characteristics that limit our ability to develop a sound, research-driven, evidence base. As a result, we remain limited in our knowledge about which treatments are effective, for which symptoms they are effective, and for which population subgroups they are most likely to be effective. This review provides a summary of identified needs and challenges in the delivery of foster carer interventions. It provides an account of current treatment components and offers a platform for the development and progression of a programme of research in an effort to advance knowledge in the area.
Logistical considerations for the arms production industry in the Middle Byzantine Empire
Authors: Dills Jordan M.
Published: October 2020

Utilizing the information recorded in the mid-tenth century Byzantine document known as De Ceremoniis, this paper will examine labour requirements for armament production in the context of a naval expedition to Crete launched by the Byzantines in AD 949. A series of interviews was conducted with experienced blacksmiths with the intention of exploring time requirements for equipment manufacture. The information provided by the De Ceremoniis, as well as that produced through the interviews, has allowed for the assessment of overall trends in the tenth century arms production industry, including labour investments, thematic and imperial production capabilities, and transportation logistics.
Mass Gathering Emergency Medicine Organization for the Union of European Football Associations’ Under-21 Championship 2019 in Bologna, Italy
Authors: Imbriaco Guglielmo , Flauto Alfonso , Bussolari Tiziano , Cordenons Fiorella , Gordini Giovanni
Published: October 2020

Football events represent a type of Mass Gathering Events (MGE) where crowd behavior, temperature and Heat Index, absence of free water, and alcohol consumption can lead to an increased need for medical assistance in participants. This report describes the environmental issues, organization, and healthcare assistance provided during the four matches of the Union of European Football Associations’ (UEFA) Under-21 tournament held in Bologna in June, 2019. The four matches had a total of 72655 spectators; 31 patients required medical assistance with a mean Patient Presentation Rate (PPR) of 0.41; Mean Transport To Hospital Rate (TTHR) of 0.04; with PPR and TTHR comparable with literature findings. Majority of patients suffered from minor injuries and illnesses, and were treated directly in stadium medical sites. Medical assistance involved volunteer rescuers, emergency nurses, and physicians; resources were efficiently allocated and provided effective care to every patient.

Climate factors, heat and humidity, the absence of free water, and increased alcohol consumption appear to be associated with increased requests for medical assistance. The retrospective analysis of a wider range of environmental factors, and the historical experience developed during similar MGEs suggest the need for a more comprehensive, improved approach for adequately assessing risk and planning the necessary healthcare resources.
CONFLICTING FORUM-SELECTION AGREEMENTS IN TREATY AND CONTRACT
Authors: Donnelly Stephen
Published: October 2020

When an investor submits a claim to arbitration under a treaty that falls within the scope of an existing, contractual forum-selection clause between it and the host State, which prevails: the agreement to arbitrate under the treaty or the contractual clause? This is a vexed and commonly arising question. This article argues that by placing it in the context of both private and public international law and reasoning from first principles it is possible to arrive at a coherent, reliable and satisfactory approach. The true question is whether the contractual clause is a waiver of the investor's right to recourse to an investment tribunal.
Tricuspid valve in valve procedure with an Edwards S3 valve© in a 10 kg child
Authors: Betrián-Blasco Pedro , Marti-Aguasca Gerard , Giralt-García Gemma
Published: October 2020

A 4-year-old child of 10 kg weight, with four previous sternotomies, presented a severe right heart failure, due to a severe regurgitation of his bioprosthetic tricuspid valve. A percutaneous tricuspid valve in valve procedure with an Edwards S3 valve was offered for compassionate use, and performed, with no complications, and significant clinical condition improvement.
Taking an Aerial View Underground
Authors: Carmichael Jady
Published: October 2020

Wisconsin geologists are testing using drones equipped with thermal cameras to measure shallow soil depths in areas prone to groundwater contamination.
Performance of GRACE Mascon Solutions in Studying Seismic Deformations
Authors: Zhang Lan , Tang He , Chang Le , Sun Wenke
Published: October 2020

GRACE (Gravity Recovery and Climate Experiment) mascon (mass concentration) solutions are widely used in cryosphere science and hydrology research. Mascon solutions have been demonstrated to perform analogous to or better than spherical harmonic (SH) solutions at the basin scale. Although the mascon solutions are expected to facilitate an improved local recovery of seismic gravity signals of large earthquakes, the application of mascon solutions to earthquake analysis remains to be investigated. In this study, we examine the performance of the mascon solutions for seismic gravity signals induced by three M9 class (2011 Tohoku‐Oki, 2004 Sumatra, and 2010 Chile) and three smaller earthquakes and compare them with SH solutions and theoretical gravity changes modeled according to the dislocation theory. We analyze the coseismic and postseismic gravity changes and conclude that the mascon solutions contain information almost identical to the SH solutions and retrieve coseismic gravity change signals with resolutions equivalent to Gaussian filter radii of 210–270 km. The mascon solutions have strengthened gravity change signals of approximately twice the strength of the SH solutions. However, mascon solution cannot fully recover the complete seismic deformation since it is still a spatially “band‐limited” data set that uses the spatial smoothing in the aggressive regularization. We found that the mascon solutions contain “seismic‐like” gravity change signals several months before the Tohoku‐Oki and Chile earthquakes occurred.
Seismic Reflection Imaging of the Low‐Angle Panamint Normal Fault System, Eastern California
Authors: Gold Ryan D. , Stephenson William J. , Briggs Richard W. , DuRoss Christopher B. , Kirby Eric , Woolery Edward , Delano Jaime , Odum Jack K.
Published: October 2020

Shallowly dipping (<30°) low‐angle normal faults (LANFs) have been documented globally; however, examples of active LANFs in continental settings are limited. The western margin of the Panamint Range in eastern California is defined by a LANF that dips west beneath Panamint Valley and has evidence of Quaternary motion. In addition, high‐angle dextral‐oblique normal faults displace middle to late Quaternary alluvial fans near the range front. To image shallow (<1 km depth), crosscutting relationships between the low‐ and high‐angle faults along the range front, we acquired two high‐resolution P wave seismic reflection profiles. The northern, 4.6‐km‐long profile crosses the 2‐km‐wide Wildrose graben and the southern, 0.8‐km‐long profile extends onto the Panamint Valley playa, ~7.5 km S of Ballarat, CA. The profile across the Wildrose graben reveals a robust, low‐angle reflector interpreted to represent the LANF separating Plio‐Pleistocene alluvial fanglomerate and Proterozoic metasedimentary deposits. High‐angle faults interpreted in the seismic profile correspond to fault scarps on Quaternary alluvial fan surfaces. Interpretation of the reflection data suggests that the high‐angle faults vertically displace the LANF up to 80 m within the Wildrose graben. Similarly, the profile south of Ballarat reveals a low‐angle reflector, which appears both rotated and displaced up to 260 m by high‐angle faults. These results suggest that near the Panamint range front, the high‐angle faults are the dominant active structures. We conclude that at least at shallow (<1 km) depths, the LANF we imaged is not active today.
Household insecticide use and urinary 3-phenoxybenzoic acid levels in an elder population: a repeated measures data
Authors: Kim Jin Hee , Kim Sungroul , Hong Yun-Chul
Published: October 2020

Background

Pyrethroids are associated with adverse health consequences, even at low-dose exposures. However, there is limited evidence on pyrethroids exposure levels among vulnerable elder population and on their exposure sources.

Objective

We tried to determine pyrethroids exposure levels among Korean elders and their exposure sources.

Methods

We measured levels of 3-phenoxybenzoic acid (3-PBA), a pyrethroids metabolite, in urines repeatedly collected from 1239 Korean rural and urban elders; we also explored exposure sources for pyrethroids using questionnaire data.

Results

Our participants had high levels of 3-PBA with 446 (36.0%) of elders with 3-PBA level over 2 ng/mL of 95th percentile of the German representative populations. After adjustment for sex, age, smoking status, visit episode, and surveyed season using linear mixed effect models, household insecticide spray use was significantly associated with 3-PBA level (β = 0.03 and p = 0.02) and the association was apparent only for females (β = 0.03 and p = 0.03). In the analyses for nonlinear relationships using generalized additive mixed models, there was a J-shape change in 3-PBA level by insecticide spray use (p < 0.01 both in total population and in females).

Significance

Household insecticide spray was a predominant exposure source for pyrethroids at community level among Korean elders, warning more stringent control for frequently exposed environmental factors for pyrethroids including insecticide spray.
Advances in targeted therapy for esophageal cancer
Authors: Yang Yan-Ming , Hong Pan , Xu Wen Wen , He Qing-Yu , Li Bin
Published: October 2020

Esophageal cancer (EC) is one of the most lethal cancers in the world, and its morbidity and mortality rates rank among the top ten in China. Currently, surgical resection, radiotherapy and chemotherapy are the primary clinical treatments for esophageal cancer. However, outcomes are still unsatisfactory due to the limited efficacy and severe adverse effects of conventional treatments. As a new type of approach, targeted therapies have been confirmed to play an important role in the treatment of esophageal cancer; these include cetuximab and bevacizumab, which target epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF), respectively. In addition, other drugs targeting surface antigens and signaling pathways or acting on immune checkpoints have been continuously developed. For example, trastuzumab, a monoclonal antibody targeting human epidermal growth factor receptor 2 (HER-2), has been approved by the Food and Drug Administration (FDA) as a first-line treatment of HER-2-positive cancer. Moreover, the PD-L1 inhibitor pembrolizumab has been approved as a highly efficient drug for patients with PD-L1-positive or advanced esophageal squamous cell carcinoma (ESCC). These novel drugs can be used alone or in combination with other treatment strategies to further improve the treatment efficacy and prognosis of cancer patients. Nevertheless, adverse events, optimal dosages and effective combinations still need further investigation. In this review, we expound an outline of the latest advances in targeted therapies of esophageal cancer and the mechanisms of relevant drugs, discuss their efficacy and safety, and provide a clinical rationale for precision medicine in esophageal cancer.
Biodiversity of key-stone phylotypes determines crop production in a 4-decade fertilization experiment
Authors: Fan Kunkun , Delgado-Baquerizo Manuel , Guo Xisheng , Wang Daozhong , Zhu Yong-guan , Chu Haiyan
Published: October 2020

Cropping systems have fertilized soils for decades with undetermined consequences for the productivity and functioning of terrestrial ecosystems. One of the critical unknowns is the role of soil biodiversity in controlling crop production after decades of fertilization. This knowledge gap limits our capacity to assess how changes in soil biodiversity could alter crop production and soil health in changing environments. Here, we used multitrophic ecological networks to investigate the importance of soil biodiversity, in particular, the biodiversity of key-stone taxa in controlling soil functioning and wheat production in a 35-year field fertilization experiment. We found strong and positive associations between soil functional genes, crop production and the biodiversity of key-stone phylotypes; soils supporting a larger number of key-stone nematode, bacteria and fungi phylotypes yielded the highest wheat production. These key-stone phylotypes were also positively associated with plant growth (phototrophic bacteria, nitrogen fixers) and multiple functional genes related to nutrient cycling. The retrieved information on the genomes clustered with key-stone bacterial phylotypes indicated that the key-stone taxa had higher gene copies of oxidoreductases (participating most biogeochemical cycles of ecosystems and linking to microbial energetics) and 71 essential functional genes associated with carbon, nitrogen, phosphorus, and sulfur cycling. Altogether, our work highlights the fundamental role of the biodiversity of key-stone phylotypes in maintaining soil functioning and crop production after several decades of fertilization, and provides a list of key-stone phylotypes linking to crop production and soil nutrient cycling, which could give science-based guidance for sustainable food production.
Hindlimb unloading causes regional loading-dependent changes in osteocyte inflammatory cytokines that are modulated by exogenous irisin treatment
Authors: Metzger Corinne E. , Anand Narayanan S. , Phan Peter H. , Bloomfield Susan A.
Published: October 2020

Disuse-induced bone loss is characterized by alterations in bone turnover. Accruing evidence suggests that osteocytes respond to inflammation and express and/or release pro-inflammatory cytokines; however, it remains largely unknown whether osteocyte inflammatory proteins are influenced by disuse. The goals of this project were (1) to assess osteocyte pro-inflammatory cytokines in the unloaded hindlimb and loaded forelimb of hindlimb unloaded rats, (2) to examine the impact of exogenous irisin during hindlimb unloading (HU). Male Sprague Dawley rats (8 weeks old, n = 6/group) were divided into ambulatory control, HU, and HU with irisin (HU + Ir, 3×/week). Lower cancellous bone volume, higher osteoclast surfaces (OcS), and lower bone formation rate (BFR) were present at the hindlimb and 4th lumbar vertebrae in the HU group while the proximal humerus of HU rats exhibited no differences in bone volume, but higher BFR and lower OcS vs. Con. Osteocyte tumor necrosis factor-α (TNF-α), interleukin-17 (IL-17), RANKL, and sclerostin were elevated in the cancellous bone of the distal femur of HU rats vs. Con, but lower at the proximal humerus in HU rats vs. Con. Exogenous irisin treatment increased BFR, and lowered OcS and osteocyte TNF-α, IL-17, RANKL, and sclerostin in the unloaded hindlimb of HU + Ir rats while having minimal changes in the humerus. In conclusion, there are site-specific and loading-specific alterations in osteocyte pro-inflammatory cytokines and bone turnover with the HU model of disuse bone loss, indicating a potential mechanosensory impact of osteocyte TNF-α and IL-17. Additionally, exogenous irisin significantly reduced the pro-inflammatory status of the unloaded hindlimb.
Simulation of liquid flow with a combination artificial intelligence flow field and Adams–Bashforth method
Authors: Babanezhad Meisam , Behroyan Iman , Nakhjiri Ali Taghvaie , Marjani Azam , Shirazian Saeed
Published: October 2020

Direct numerical simulation (DNS) of particle hydrodynamics in the multiphase industrial process enables us to fully learn the process and optimize it on the industrial scale. However, using high-resolution computational calculations for particle movement and the interaction between the solid phase and other phases in fine timestep is limited to excellent computational resources. Solving the Eulerian flow field as a source of solid particle movement can be very time-consuming. However, by the revolution of the fast and accurate learning process, the Eulerian domain can be computed by smart modeling in a very short computational time. In this work, using the machine learning method, the flow field in the square shape cavity is trained, and then the Eulerian framework is replaced with a machine learning method to generate the artificial intelligence (AI) flow field. Then the Lagrangian framework is coupled with this AI flow field, and we simulate particle motion through the fully AI framework. The Adams–Bashforth finite element method is used as a conventional CFD method (Eulerian framework) to simulate the flow field in the cavity. After simulating fluid flow, the ANFIS method is used as an AI model to train the Eulerian data-set and represents AI fluid flow (framework). The Lagrangian framework is coupled with the AI method, and the particle freely migrates through this artificial framework. The results reveal that there is a great agreement between Euler-Lagrangian and AI- Lagrangian in the cavity. We also found that there is an excellent agreement between AI overview with the Adams–Bashforth approach, and the new combination of machine learning and CFD method can accelerate the calculation of the flow field in the square-shaped cavity. AI model can mimic the vortex structure in the cavity, where there is a zero-velocity structure in the center of the domain and maximum velocity near the moving walls.
Synovial fluid lubricin increases in spontaneous canine cruciate ligament rupture
Authors: Wang Yuyan , Gludish David W. , Hayashi Kei , Todhunter Rory J. , Krotscheck Ursula , Johnson Philippa J. , Cummings Bethany P. , Su Jin , Reesink Heidi L.
Published: October 2020

Lubricin is an important boundary lubricant and chondroprotective glycoprotein in synovial fluid. Both increased and decreased synovial fluid lubricin concentrations have been reported in experimental post-traumatic osteoarthritis (PTOA) animal models and in naturally occurring joint injuries in humans and animals, with no consensus about how lubricin is altered in different species or injury types. Increased synovial fluid lubricin has been observed following intra-articular fracture in humans and horses and in human late-stage osteoarthritis; however, it is unknown how synovial lubricin is affected by knee-destabilizing injuries in large animals. Spontaneous rupture of cranial cruciate ligament (RCCL), the anterior cruciate ligament equivalent in quadrupeds, is a common injury in dogs often accompanied by OA. Here, clinical records, radiographs, and synovial fluid samples from 30 dogs that sustained RCCL and 9 clinically healthy dogs were analyzed. Synovial fluid lubricin concentrations were nearly 16-fold greater in RCCL joints as compared to control joints, while IL-2, IL-6, IL-8, and TNF-α concentrations did not differ between groups. Synovial fluid lubricin concentrations were correlated with the presence of radiographic OA and were elevated in three animals sustaining RCCL injury prior to the radiographic manifestation of OA, indicating that lubricin may be a potential biomarker for early joint injury.
Ninjurin 1 dodecamer peptide containing the N-terminal adhesion motif (N-NAM) exerts proangiogenic effects in HUVECs and in the postischemic brain
Authors: Kim Seung-Woo , Lee Hye-Kyung , Seol Song-I. , Davaanyam Dashdulam , Lee Hahnbie , Lee Ja-Kyeong
Published: October 2020

Nerve injury-induced protein 1 (Ninjurin 1, Ninj1) is a cell adhesion molecule responsible for cell-to-cell interactions between immune cells and endothelial cells. In our previous paper, we have shown that Ninj1 plays an important role in the infiltration of neutrophils in the postischemic brain and that the dodecamer peptide harboring the Ninj1 N-terminal adhesion motif (N-NAM, Pro26-Asn37) inhibits infiltration of neutrophils in the postischemic brain and confers robust neuroprotective and anti-inflammatory effects. In the present study, we examinedt the pro-angiogenic effect of N-NAM using human umbilical vein endothelial cells (HUVECs) and rat MCAO (middle cerebral artery occlusion) model of stroke. We found that N-NAM promotes proliferation, migration, and tube formation of HUVECs and demonstrate that the suppression of endogenous Ninj1 is responsible for the N-NAM-mediated pro-angiogenic effects. Importantly, a pull-down assay revealed a direct binding between exogenously delivered N-NAM and endogenous Ninj1 and it is N-terminal adhesion motif dependent. In addition, N-NAM activated the Ang1-Tie2 and AKT signaling pathways in HUVECs, and blocking those signaling pathways with specific inhibitors suppressed N-NAM-induced tube formation, indicating critical roles of those signaling pathways in N-NAM-induced angiogenesis. Moreover, in a rat MCAO model, intranasal administration of N-NAM beginning 4 days post-MCAO (1.5 µg daily for 3 days) augmented angiogenesis in the penumbra of the ipsilateral hemisphere of the brain and significantly enhanced total vessel lengths, vessel densities, and pro-angiogenic marker expression. These results demonstrate that the 12-amino acid Ninj1 peptide, which contains the N-terminal adhesion motif of Ninj1, confers pro-angiogenic effects and suggest that those effects might contribute to its neuroprotective effects in the postischemic brain.
An innovative approach for determining the customized refractive index of ectatic corneas in cataractous patients
Authors: Pirhadi Shiva , Maghooli Keivan , Jadidi Khosrow
Published: October 2020

The aim of this study is to determine the customized refractive index of ectatic corneas and also propose a method for determining the corneal and IOL power in these eyes. Seven eyes with moderate and severe corneal ectatic disorders, which had been under cataract surgery, were included. At least three months after cataract surgery, axial length, cornea, IOL thickness and the distance between IOL from cornea, and aberrometry were measured. All the measured points of the posterior and anterior parts of the cornea converted to points cloud and surface by using the MATLAB and Solidworks software. The implanted IOLs were designed by Zemax software. The ray tracing analysis was performed on the customized eye models, and the corneal refractive index was determined by minimizing the difference between the measured aberrations from the device and resulted aberrations from the simulation. Then, by the use of preoperative corneal images, corneal power was calculated by considering the anterior and posterior parts of the cornea and refractive index of 1.376 and the customized corneal refractive index in different regions and finally it was entered into the IOL power calculation formulas. The corneal power in the 4 mm region and the Barrett formula resulted the prediction error of six eyes within ± 1 diopter. It seems that using the total corneal power along with the Barrett formula can prevent postoperative hyperopic shift, especially in eyes with advanced ectatic disorders.
Integrative ecological and molecular analysis indicate high diversity and strict elevational separation of canopy beetles in tropical mountain forests
Authors: Floren Andreas , von Rintelen Thomas , Hebert Paul D. N. , de Araujo Bruno Cancian , Schmidt Stefan , Balke Michael , Narakusumo Raden Pramesa , Peggie Djunijanti , Ubaidillah Rosichon , von Rintelen Kristina , Müller Tobias
Published: October 2020

Tropical mountain forests contribute disproportionately to terrestrial biodiversity but little is known about insect diversity in the canopy and how it is distributed between tree species. We sampled tree-specific arthropod communities from 28 trees by canopy fogging and analysed beetle communities which were first morphotyped and then identified by their DNA barcodes. Our results show that communities from forests at 1100 and 1700 m a.s.l. are almost completely distinct. Diversity was much lower in the upper forest while community structure changed from many rare, less abundant species to communities with a pronounced dominance structure. We also found significantly higher beta-diversity between trees at the lower than higher elevation forest where community similarity was high. Comparisons on tree species found at both elevations reinforced these results. There was little species overlap between sites indicating limited elevational ranges. Furthermore, we exploited the advantage of DNA barcodes to patterns of haplotype diversity in some of the commoner species. Our results support the advantage of fogging and DNA barcodes for community studies and underline the need for comprehensive research aimed at the preservation of these last remaining pristine forests.
Assembly of the durian chloroplast genome using long PacBio reads
Authors: Shearman Jeremy R. , Sonthirod Chutima , Naktang Chaiwat , Sangsrakru Duangjai , Yoocha Thippawan , Chatbanyong Ratchanee , Vorakuldumrongchai Siriporn , Chusri Orwintinee , Tangphatsornruang Sithichoke , Pootakham Wirulda
Published: October 2020

We have assembled the complete sequence of the Durio zibethinus chloroplast genome using long PacBio reads. Durian is a valuable commercial tree that produces durian fruit, which is popular in Southeast Asia. The chloroplast genome assembled into a single 143 kb cyclic contig that contained 111 genes. There were 46 short direct repeats (45 to 586 bp) and five short inverted repeats (63 to 169 bp). The long reads that were used for the assembly span the entire chloroplast with > 10 kb overlaps and multiple long reads join the start of the contig to the end of the contig. The durian chloroplast was found to lack the large inverted repeat that is common in chloroplast genomes. An additional 24 durian varieties were sequenced and compared to the assembly and found to also lack the large inverted repeat. There were nine SNPs among the varieties.
Haploinsufficiency due to a novel ACO2 deletion causes mitochondrial dysfunction in fibroblasts from a patient with dominant optic nerve atrophy
Authors: Neumann Marie Anne-Catherine , Grossmann Dajana , Schimpf-Linzenbold Simone , Dayan Dana , Stingl Katarina , Ben-Menachem Reut , Pines Ophry , Massart François , Delcambre Sylvie , Ghelfi Jenny , Bohler Jill , Strom Tim , Kessel Amit , Azem Abdussalam , Schöls Ludger , Grünewald Anne , Wissinger Bernd , Krüger Rejko
Published: October 2020

ACO2 is a mitochondrial protein, which is critically involved in the function of the tricarboxylic acid cycle (TCA), the maintenance of iron homeostasis, oxidative stress defense and the integrity of mitochondrial DNA (mtDNA). Mutations in the ACO2 gene were identified in patients suffering from a broad range of symptoms, including optic nerve atrophy, cortical atrophy, cerebellar atrophy, hypotonia, seizures and intellectual disabilities. In the present study, we identified a heterozygous 51 bp deletion (c.1699_1749del51) in ACO2 in a family with autosomal dominant inherited isolated optic atrophy. A complementation assay using aco1-deficient yeast revealed a growth defect for the mutant ACO2 variant substantiating a pathogenic effect of the deletion. We used patient-derived fibroblasts to characterize cellular phenotypes and found a decrease of ACO2 protein levels, while ACO2 enzyme activity was not affected compared to two age- and gender-matched control lines. Several parameters of mitochondrial function, including mitochondrial morphology, mitochondrial membrane potential or mitochondrial superoxide production, were not changed under baseline conditions. However, basal respiration, maximal respiration, and spare respiratory capacity were reduced in mutant cells. Furthermore, we observed a reduction of mtDNA copy number and reduced mtDNA transcription levels in ACO2-mutant fibroblasts. Inducing oxidative stress led to an increased susceptibility for cell death in ACO2-mutant fibroblasts compared to controls. Our study reveals that a monoallelic mutation in ACO2 is sufficient to promote mitochondrial dysfunction and increased vulnerability to oxidative stress as main drivers of cell death related to optic nerve atrophy.
Towards refining Raman spectroscopy-based assessment of bone composition
Authors: Shah Furqan A.
Published: October 2020

Various compositional parameters are derived using intensity ratios and integral area ratios of different spectral peaks and bands in the Raman spectrum of bone. The$$\nu $$ν1-,$$\nu $$ν2-,$$\nu $$ν3-,$$\nu $$ν4PO43−, and$$\nu_{1} $$ν1CO32−bands represent the inorganic phase while amide I, amide III, Proline, Hydroxyproline, Phenylalanine, δ(CH3), δ(CH2), and$$\nu $$ν(C–H) represent the organic phase. Here, using high-resolution Raman spectroscopy, it is demonstrated that all PO43−bands of bone either partially overlap with or are positioned close to spectral contributions from the organic component. Assigned to the organic component, a shoulder at 393 cm−1compromises accurate estimation of$$\nu $$ν2PO43−integral area, i.e., phosphate/apatite content, with implications for apatite-to-collagen and carbonate-to-phosphate ratios. Another feature at 621 cm−1may be inaccurately interpreted as$$\nu $$ν4PO43−band broadening. In the 1020–1080 cm−1range, the ~ 1047 cm−1$$\nu $$ν3PO43−sub-component is obscured by the 1033 cm−1Phenylalanine peak, while the ~ 1076 cm−1$$\nu $$ν3PO43−sub-component is masked by the$$\nu $$ν1CO32−band. With$$\nu $$ν1PO43−peak broadening,$$\nu $$ν2PO43−integral area increases exponentially and individual peaks comprising the$$\nu $$ν4PO43−band merge together. Therefore,$$\nu $$ν2PO43−and$$\nu $$ν4PO43−band profiles are sensitive to changes in mineral crystallinity.
The effects of fructose and metabolic inhibition on hepatocellular carcinoma
Authors: Dewdney Brittany , Alanazy Mohammed , Gillman Rhys , Walker Sarah , Wankell Miriam , Qiao Liang , George Jacob , Roberts Alexandra , Hebbard Lionel
Published: October 2020

Hepatocellular carcinoma is rapidly becoming one of the leading causes of cancer-related deaths, largely due to the increasing incidence of non-alcoholic fatty liver disease. This in part may be attributed to Westernised diets high in fructose sugar. While many studies have shown the effects of fructose on inducing metabolic-related liver diseases, little research has investigated the effects of fructose sugar on liver cancer metabolism. The present study aimed to examine the metabolic effects of fructose on hepatocellular carcinoma growth in vitro and in vivo. Fructose sugar was found to reduce cell growth in vitro, and caused alterations in the expression of enzymes involved in the serine-glycine synthesis and pentose phosphate pathways. These biosynthesis pathways are highly active in cancer cells and they utilise glycolytic by-products to produce energy and nucleotides for growth. Hence, the study further investigated the efficacy of two novel drugs that inhibit these pathways, namely NCT-503 and Physcion. The study is the first to show that the combination treatment of NCT-503 and Physcion substantially inhibited hepatocellular carcinoma growth in vitro and in vivo. The combination of fructose diet and metabolism-inhibiting drugs may provide a unique metabolic environment that warrants further investigation in targeting hepatocellular carcinoma.
SNP-SNP interactions of oncogenic long non-coding RNAs HOTAIR and HOTTIP on gastric cancer susceptibility
Authors: Abdi Esmat , Latifi-Navid Saeid , Zahri Saber , Kholghi-Oskooei Vahid , Mostafaiy Behdad , Yazdanbod Abbas , Pourfarzi Farhad
Published: October 2020

Genetic variants within oncogenic long non-coding RNAs HOTAIR and HOTTIP may affect their gene expression levels, thereby modifying genetic susceptibility to gastric cancer (GC). In a hospital-based study in Ardabil—a very high-risk area in North-West Iran, 600 blood samples from 300 GC patients and 300 healthy controls were recruited for genotyping. Seven HOTAIR (i.e., rs17720428, rs7958904, rs1899663, and rs4759314) and HOTTIP (i.e., rs3807598, rs17501292, and rs1859168) ‘tag’ single nucleotide polymorphisms (SNPs) were genotyped by the Infinium HTS platform. The rs17720428, rs7958904, and rs1899663 tagSNPs significantly increased GC risk under dominant models by 1.5-, 1.57-, and 1.5-fold, respectively. The G-C-T-A haplotype of HOTAIR tagSNPs increased the risk of GC by 1.31-fold. No significant association was found between HOTTIP SNPs and the risk of GC. HOTAIR and HOTTIP variants were also not associated with any clinicopathologic characteristics. The SNP-SNP interaction of HOTAIR rs17720428/rs7958904 with HOTTIP rs1859168 was associated with an increased risk of GC (rs17720428 TG-rs1859168 CC, OR = 1.76; rs7958904 GC-rs1859168 CC, OR = 1.85; rs7958904 CC-rs1859168 CC, OR = 1.86). Interestingly, the SNP-SNP interaction of HOTAIR rs1899663 with HOTTIP rs1859168 strongly increased the risk of GC (rs1899663 GT-rs1859168 CC, OR = 4.3; rs1899663 TT-rs1859168 CC, OR = 9.37; rs1899663 TT-rs1859168 CA, OR = 6.59). We showed that the HOTAIR rs17720428, rs7958904, and rs1899663 tagSNPs and their interactions with the HOTTIP rs1859168 polymorphism significantly increased the risk of GC. Specifically, novel SNP-SNP interactions between HOTAIR and HOTTIP tagSNPs have a larger impact than individual SNP effects on GC risk, thereby providing us with valuable information to reveal potential biological mechanisms for developing GC.
Immune characterization of pre-clinical murine models of neuroblastoma
Authors: Webb Emily R. , Lanati Silvia , Wareham Carol , Easton Alistair , Dunn Stuart N. , Inzhelevskaya Tatyana , Sadler Freja M. , James Sonya , Ashton-Key Margaret , Cragg Mark S. , Beers Stephen A. , Gray Juliet C.
Published: October 2020

Immunotherapy offers a potentially less toxic, more tumor-specific treatment for neuroblastoma than conventional cytotoxic therapies. Accurate and reproducible immune competent preclinical models are key to understanding mechanisms of action, interactions with other therapies and mechanisms of resistance to immunotherapy. Here we characterized the tumor and splenic microenvironment of two syngeneic subcutaneous (NXS2 and 9464D), and a spontaneous transgenic (TH-MYCN) murine model of neuroblastoma, comparing histological features and immune infiltrates to previously published data on human neuroblastoma. Histological sections of frozen tissues were stained by immunohistochemistry and immunofluorescence for immune cell markers and tumor architecture. Tissues were dissociated by enzymatic digestion, stained with panels of antibodies to detect and quantify cancer cells, along with lymphocytic and myeloid infiltration by flow cytometry. Finally, we tested TH-MYCN mice as a feasible model for immunotherapy, using prior treatment with cyclophosphamide to create a therapeutic window of minimal residual disease to favor host immune development. Immune infiltration differed significantly between all the models. TH-MYCN tumors were found to resemble immune infiltration in human tumors more closely than the subcutaneous models, alongside similar GD2 and MHC class I expression. Finally, TH-MYCN transgenic mice were administered cyclophosphamide alone or in combination with an anti-GD2 or anti-4-1BB monoclonal antibody, which resulted in increase in survival in both combination therapies. The TH-MYCN transgenic mouse is a promising in vivo model for testing immunotherapy compounds and combination therapy in a preclinical setting.
Arabidopsis phenotyping reveals the importance of alcohol dehydrogenase and pyruvate decarboxylase for aerobic plant growth
Authors: Ventura Irene , Brunello Luca , Iacopino Sergio , Valeri Maria Cristina , Novi Giacomo , Dornbusch Tino , Perata Pierdomenico , Loreti Elena
Published: October 2020

Alcohol dehydrogenase (ADH) and pyruvate decarboxylase (PDC) are key to the establishment of the fermentative metabolism in plants during oxygen shortage. Most of the evidence that both ADH and PDC are required for plant tolerance to hypoxia comes from experiments performed by limiting oxygen in the environment, such as by exposing plants to gaseous hypoxia or to waterlogging or submergence. However, recent experiments have shown that hypoxic niches might exist in plants grown in aerobic conditions. Here, we investigated the importance of ADH and PDC for plant growth and development under aerobic conditions, long-term waterlogging and short-term submergence. Data were collected after optimizing the software associated with a commercially-available phenotyping instrument, to circumvent problems in separation of plants and background pixels based on colour features, which is not applicable for low-oxygen stressed plants due to the low colour contrast of leaves with the brownish soil. The results showed that the growth penalty associated with the lack of functional ADH1 or both PDC1 and PDC2 is greater under aerobic conditions than in hypoxia, highlighting the importance of fermentative metabolism in plants grown under normal, aerobic conditions.
Modeling the dynamics of antibody–target binding in living tumors
Authors: Tang Yu , Cao Yanguang
Published: October 2020

Antibodies have become an attractive class of therapeutic agents for solid tumors, mainly because of their high target selectivity and affinity. The target binding properties of antibodies are critical for their efficacy and toxicity. Our lab has developed a bioluminescence resonance energy transfer (BRET) imaging approach that directly supports the measurement of the binding dynamics between antibodies and their targets in the native tumor environment. In the present study, we have developed a spatially resolved computational model analyzing the longitudinal BRET imaging data of antibody–target binding and exploring the mechanisms of biphasic binding dynamics between a model antibody cetuximab and its target, the epidermal growth factor receptor (EGFR). The model suggested that cetuximab is bound differently to EGFR in the stroma-rich area than in stroma-poor regions, which was confirmed by immunofluorescence staining. Compared to the binding in vitro, cetuximab bound to EGFR to a “slower-but-tighter” degree in the living tumors. These findings have provided spatially resolved characterizations of antibody–target binding in living tumors and have yielded many mechanistic insights into the factors that affect antibody interactions with its targets and treatment efficacy.
On the interpretability of predictors in spatial data science: the information horizon
Authors: Behrens Thorsten , Viscarra Rossel Raphael A.
Published: October 2020

Two important theories in spatial modelling relate to structural and spatial dependence. Structural dependence refers to environmental state-factor models, where an environmental property is modelled as a function of the states and interactions of environmental predictors, such as climate, parent material or relief. Commonly, the functions are regression or supervised classification algorithms. Spatial dependence is present in most environmental properties and forms the basis for spatial interpolation and geostatistics. In machine learning, modelling with geographic coordinates or Euclidean distance fields, which resemble linear variograms with infinite ranges, can produce similar interpolations. Interpolations do not lend themselves to causal interpretations. Conversely, with structural modeling, one can, potentially, extract knowledge from the modelling. Two important characteristics of such interpretable environmental modelling are scale and information content. Scale is relevant because very coarse scale predictors can show nearly infinite ranges, falling out of what we call the information horizon, i.e. interpretation using domain knowledge isn’t possible. Regarding information content, recent studies have shown that meaningless predictors, such as paintings or photographs of faces, can be used for spatial environmental modelling of ecological and soil properties, with accurate evaluation statistics. Here, we examine under which conditions modelling with such predictors can lead to accurate statistics and whether an information horizon can be derived for scale and information content.