bluuebunny/crossref_metadata_2025 huggingface dataset:
A Common Approach to Three Open Problems in Number Theory
Authors: Tyszka Apoloniusz
Published: April 2023

The following system of equations {x_1 \cdot x_1=x_2, x_2 \cdot x_2=x_3, 2^{2^{x_1}}=x_3, x_4 \cdot x_5=x_2, x_6 \cdot x_7=x_2} has exactly one solution in ({\mathbb N}\{0,1})^7, namely (2,4,16,2,2,2,2). Hypothesis 1 states that if a system of equations S \subseteq {x_i \cdot x_j=x_k: i,j,k \in {1,...,7}} \cup {2^{2^{x_j}}=x_k: j,k \in {1,...,7}} has at most five equations and at most finitely many solutions in ({\mathbb N}\{0,1})^7, then each such solution (x_1,...,x_7) satisfies x_1,...,x_7 \leq 16. Hypothesis 1 implies that there are infinitely many composite numbers of the form 2^{2^{n}}+1. Hypotheses 2 and 3 are of similar kind. Hypothesis 2 implies that if the equation x!+1=y^2 has at most finitely many solutions in positive integers x and y, then each such solution (x,y) belongs to the set {(4,5),(5,11),(7,71)}. Hypothesis 3 implies that if the equation x(x+1)=y! has at most finitely many solutions in positive integers x and y, then each such solution (x,y) belongs to the set {(1,2),(2,3)}. We describe semi-algorithms sem_j (j=1,2,3) such that Hypothesis j holds if and only if sem_j prints consecutive positive integers starting from 1.
PARP1: New Drug Development Opportunities for an Old Target
Authors: Iglesias Pablo , Seoane Marcos , Golán-Cancela Irene , Fraga Maximo , Arce Víctor M. , Costoya Jose A.
Published: April 2023

In recent years, new therapies have been developed based on molecules that target mo-lecular mechanisms involved in both the initiation and maintenance of the oncogenic process. Among these molecules are the poly (ADP-ribose) polymerase 1 (PARP1) inhibitors. PARP1 has emerged as a target with great therapeutic potential for some tumor types, drawing attention to this enzyme and resulting in many small molecule inhibitors of its enzymatic activity. Thus, many PARP inhibitors are currently in clinical trials for the treatment of homologous recombina-tion (HR)-deficient tumors, BRCA-related cancers, taking advantage of synthetic lethality. In ad-dition, several novel cellular functions unrelated to its role in DNA repair have been described, including post-translational modification of transcription factors, or acting through pro-tein-protein interactions as a co-activator or co-repressor of transcription. Previously, we report-ed that this enzyme may play a key role as a transcriptional co-activator of an important compo-nent of cell cycle regulation, the transcription factor E2F1. Here, we show that PARP inhibitors, which interfere with its activity in cell cycle regulation, do so without affecting its enzymatic function.
Potential Use of Guarana-Loaded Liposomes in Topical Applica-Tions: Toxicity Profile Assessment Using Different Skin Cell Lines
Authors: Roggia Isabel , Gomes Patrícia , Dalcin Ana Julia Figueiro , Ourique Aline Ferreira , Mânica Da Cruz Ivana Beatrice , Esteves Ribeiro Euler , Mitjans Montserrat , Vinardell Maria Pilar
Published: April 2023

The objective of this study was to analyze the in vitro stability and toxicity of liposomes containing guarana in skin cell lines. The liposomes were produced by the reverse phase evaporation method containing 1 mg/mL guarana. The stability of the liposomes was evaluated by physical-chemical parameters for up to 90 d using three different storage conditions. The cytotoxicity of guarana (GL), liposomes (B-Lip), and guarana-loaded liposomes (G-Lip) was evaluated on spontaneously immortalized human keratinocyte cell lines (HaCaT), murine swiss albino fibroblasts (3T3), and human fibroblast (1BR.3.G). The evaluation was performed using cellular viability analysis. The techniques used were 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and neutral red capturing (NRU) and the analyses were conducted after 24, 48, and 72 h exposure of these cells to the different treatments. The G-Lip exhibited physical-chemical stability for 60 d when the samples were stored in a refrigerator. The GL, B-Lip, and G-Lip demonstrated low cytotoxicity in the three cell cultures tested since a low reduction in cell viability was only observed at the highest concentrations. In addition, greater cell damage was observed for B-Lip; however, guarana protects cells from this damage. Thus, G-Lip structures can be considered as promising systems for topical applications.
Tuning SERS Signal via Substrate Structuring: Valves of Different Diatom Species with Ultrathin Gold Coating
Authors: Gilic Martina , Ghobara Mohamed , Reissig Louisa
Published: April 2023

The discovered light modulation capabilities of diatom silicious valves make them an excellent toolkit for photonic devices and applications. In this work, a reproducible surface-enhanced Raman-scattering (SERS) enhancement was achieved with hybrid substrates employing diatom silica valves coated with an ultrathin uniform gold film. Three structurally different hybrid substrates, based on the valves of three dissimilar diatom species, have been compared to elucidate the structural contribution to SERS enhancement. The comparative analysis of obtained results showed that substrates containing cylindrical Aulacoseira sp. valves achieved the highest enhancement up to 14-fold. Numerical analysis based on the frequency domain finite element method was carried out to supplement the experimental results. Our results demonstrate that diatom valves of different shapes can enhance the SERS signal, offering a toolbox for SERS-based sensors, where the magnitude of the enhancement depends on valve geometry and ultrastructure.
An Integrated vMF Embedding and VOS Framework for Robust Pedestrian Re-Identification and Out-of-Distribution Detection
Authors: Bouzid Abdelhamid , Sierra-Sosa Daniel , Elmaghraby Adel
Published: April 2023

In recent years, pedestrian re-identification has gained a lot of interest due to its importance for many purposes such as security and safety. Many types of solutions have been proposed to solve this problem, where the majority are based on a features extraction such Convolution Neural Networks (CNNs). These approaches assume that only the identities that are in the training data can be recognized. The pedestrians in the training data are called In distribution (ID). However, in real world scenarios, new pedestrians and objects can appear in the scene and the model should detect them as Out Of Distribution (OOD). In our previous study , we proposed a pedestrian re-identification based on von-Mises Fisher (vMF) distribution. Each identity is embedded in the unit sphere as a compact vMF distribution far from other identities distributions. The embedding is done through a base CNN. Recently, proposed a framework called Virtual Outlier Synthetic (VOS), that detects OOD based on synthesising virtual outlier in the embedding space in an online manner. Their approach assumes that the samples from the same object maps to a compact space. This assumption aligns with the vMF based approach. Therefore, in this paper, we revisited the vMF approach and merged with VOS in order to detect OOD data points. We present our approach to merge both frameworks. We conducted several experiments to evaluate our proposed framework. Results showed that our framework was able to detect new pedestrian that do not exist in the training data in the inference phase. It also slightly helped to improve the re-identification performance.
The Generation Time and Accumulations of Lower Paleozoic Petroleum in Sichuan and Tarim Basin Determined by Re–Os Isotopic Dating
Authors: Wang Jie , Ma Liangbang , Tao Cheng , Liu Wenhui , Dong Qingwei
Published: April 2023

With the targets of petroleum exploration transferred to the deep and ancient strata, abundant oil and gas resources have been found in the Lower Paleozoic and older strata in central and western China. Due to complex evolutionary processes including multiple episodes of hydrocarbon accumulation and ubiquitously accompanied by secondary alterations, significant uncertainties were remained for the generation time and accumulation processes of these revealed petroleum. In this paper, relative pure Re and Os elements existing in the asphaltene fractions of Lower Cambrian solid bitumen collected from the Guangyuan area, western Sichuan Basin, SW China and another Middle–Lower Ordovician heavy oils in the Aiding area of the Tahe oilfield in the Tarim Basin, NW China were successfully obtained by the sample pre-treatments, and Re–Os isotopic analysis was subsequently carried out for the dating of these two petroleum. The Re–Os isotopic composition indicates a generation time of Guangyuan bitumen to locate between 572 Ma and 559 Ma, corresponding to the late Sinian period of Neoproterozoic era. By the means of Re–Os isochron ages, initial 187Os/188Os ratios, and carbon isotopic compositions, the Lower Cambrian bitumen is supposed to be originated from source rocks of the Doushantuo Formation in the Sinian strata and subsequently migrated into the reservoirs of Dengying Formation. These previously reserved petroleum had been transformed to present bitumen by the destruction of reservoirs caused by tectonic uplift. The Re–Os dating results of Middle–Lower Ordovician heavy oil of Tarim Basin supposed that it was formed between 450 Ma to 436 Ma, corresponding to the Late Ordovician–Early Silurian system, and the generated petroleum is likely to migrate into the Middle–Lower Ordovician karst reservoirs to form early oil reservoirs. With tectonic uplift, these oil reservoirs were degraded and reformed to be present heavy oil reservoirs.
Cytokinin Signaling Are Required for Multi-Main Stems Development in Brassica napus L.
Authors: Wang Qian , Xue Na , Sun Chao , Tao Jing , Mi Chao , Yuan Yi , Pan Xiangwei , Gui Min , Long Ronghua , Ding Renzhan , Li Shikai , Lin Liangbin
Published: April 2023

Rapeseed (Brassica napus L.) is a globally important oilseed crop with various uses, including consumption of its succulent stems as a seasonal vegetable, but its uniaxial branching habit limits the stem yield. Therefore, developing a multi-stem rapeseed variety has become increasingly crucial. In this study, a nature mutant of wild type from germplasm resources with stable inheritance of the multi-stem trait (MS) was obtained and showed abnormal shoot apical meristem (SAM) development and increased main stem number compared to WT. Histological and scanning electron microscopy analyses revealed multiple SAMs in the MS mutant, while only a single SAM was found in WT. Compared to WT, the mutant exhibited increased accumulation of cytokinins (CKs), transcriptome and RT-qPCR analyses showed the expression of genes involved in CK biosynthesis and metabolism pathways were altered in MS mutant. These findings provide insight into the mechanism of multiple main stems formation in Brassica napus L. and lay a theoretical foundation for breeding multi-main stem rapeseed vegetable varieties.
Organization of a three-level system of emergency, including emergency specialized, medical care in the constituent entities of the Russian Federation
Authors: Bagnenko S. F. , Teplov V. M. , Tsebrovskaya E. A. , Ihaev A. B. , Moskvina S. S.
Published: April 2023

Introduction. The article presents an analysis of the problem, justification of the concept and formulates the basic principles of the functioning of a three-level system for organizing the provision of emergency specialized medical care in the constituent entities of the Russian Federation, and also demonstrates the experience of using computer modeling to create it on the example of three constituent entities of the country.  

Target. Determination of possible ways to optimize the three-level system in the regions through virtual experiments.

Methods. A retrospective analysis of data on the current activities of the region was carried out, on the basis of which, with the help of computer simulation, a model of a three-level system was created and experiments aimed at its optimization were carried out.  

Results. On the basis of data on emergency patients admitted to various hospitals, a simulation model was created, a number of experiments were carried out aimed at determining the optimal redistribution of the flow of patients in need of emergency care in hospitals of the 3rd level, including in emergency situations of a biological and social nature at example of the COVID‑19 pandemic. The effectiveness of the proposed system was demonstrated, in the model it was possible to ensure the timely hospitalization of all patients in the subject to the place of providing them with comprehensive medical care.  

Conclusion. For the organization of a three-level system of emergency care, including specialized medical care, it is advisable to conduct organizational experiments using simulation modeling, which allows you to correctly plan the redistribution of patient flows, identify possible errors in the virtual model.
National Institutes of Health Funding to Departments of Orthopaedic Surgery at U.S. Medical Schools from 2015 to 2021
Authors: Imam Nareena , Sudah Suleiman Y. , Shaikh Siraj Z. , Nicholson Allen D. , Namdari Surena , Menendez Mariano E.
Published: April 2023

Background:

National Institutes of Health (NIH) funding of orthopaedic surgery departments has historically lagged behind that of other surgical disciplines. In this study, we present an updated analysis of NIH grants awarded to orthopaedic surgery departments at U.S. medical schools and an evaluation of the characteristics of NIH-funded principal investigators (PIs).

Methods:

The NIH Research Portfolio Online Reporting Tools Expenditures and Results (RePORTER) database was queried for grants awarded to orthopaedic surgery departments in the 2015 to 2021 fiscal years. Funding totals were calculated for 4 categories: award mechanism, awarding institute, recipient institute, and PI. Trends in funding from 2015 to 2021 were determined and compared with the annual NIH budget. Funding awarded to orthopaedic surgery departments was compared with awards received by other surgical specialties in 2021. The characteristics of NIH-funded PIs and co-PIs were evaluated. Funding awarded to orthopaedic surgery departments in 2021 was compared with funding in 2014 as reported in a previous study.

Results:

In 2021, 287 grants were awarded to 187 PIs at 47 orthopaedic surgery departments for a total of $104,710,841, representing 0.4% of the overall NIH budget. The top 5 departments earned $41,750,321 (39.9%) of the total NIH funding for orthopaedic surgery. From 2015 to 2021, total funding increased by 79.7% (p < 0.001), but the rate of increase was not significantly different from that of the overall annual NIH budget (p = 0.469). In 2021, grants were most commonly awarded via the R01 mechanism (70.0% of total funding), with a median annual award of $397,144 (interquartile range [IQR], $335,017 to $491,248). The majority of grants (70.0%) supported basic science research, followed by translational (12.2%), clinical (9.4%), and educational (8.4%) research. NIH funding did not vary by the gender of the PI (p = 0.505), and the proportion of female PIs was significantly greater in 2021 than in 2014 (33.9% versus 20.5%, p = 0.009). Compared with other surgical departments, orthopaedic surgery departments ranked second-lowest in terms of the total NIH funding received in 2021.

Conclusions:

NIH funding to orthopaedic surgery departments continues to be limited and lags behind that of other surgical subspecialties, which may create challenges in addressing the rising burden of musculoskeletal disease in the U.S. These findings highlight the importance of efforts to identify barriers to grant procurement in orthopaedic surgery.
A novelty Multi-Step Associated with Laplace Transform Semi Analytic Technique for Solving Generalized Non-linear Differential Equations
Authors: AL-Jizani Khalid Hammood , Abud Ahmed Hanoon
Published: April 2023

In this work, a novel technique to obtain an accurate solutions to nonlinear form by multi-step combination with Laplace-variational approach (MSLVIM) is introduced. Compared with the  traditional approach for variational it overcome all difficulties and enable to provide us more an accurate solutions with extended of the convergence region as well as covering to larger intervals which providing us a continuous representation of approximate analytic solution and it give more better information of the solution over the whole time interval. This technique is more easier for obtaining the general Lagrange multiplier with reduces the time and calculations. It converges rapidly to exact formula with simply computable terms with few time. To investigate of this technique, selected examples to show the ability, validity, accurately and effectiveness.
Heat Production Rate and Radiation Hazard Indices from Radioactive Elements in Different Types of Natural Water in Nineveh Governorate, Iraq.
Authors: Al-sofy Danya saleh Mustafa , Al-Jomaily Firas Mohammed Ali
Published: April 2023

The current study sheds light on the measurement and estimation of the radioactivity of radionuclides (238U, 226Ra, 232Th, and 40k) in natural waters of different regions of Nineveh Governorate in Iraq.15 samples were collected from different sources of natural waters, where gamma-ray spectroscopy was used using NaI)TI) sodium iodide detector to determine the concentration of radioactivity in the samples. According to the results, the radioactivity concentration in the tested water sample were ​​ranged from 0.36 ± 0.04-1.57 ± 0.09with an average value of 0.69 ± 0.06 Bq/l for 238U, and 2.9 ± 0.02-0.88 ± 0.03 with an average value of 0.65 ± 0.03 Bq/l for 226Ra Bq/l, and 0.48 ± 0.04-1.36 ± 0.06 with an average value of 0.88 ± 0.05 Bq/l for 232Th, while for 40K 13.00 ± 0.69-36.89 ± 1.12 with an average value of 25.1 ± 0.95 Bq/l, respectively. The results obtained from the water samples are below the safe and standard limits established by UNSCEAR. In addition to calculating the radiological hazard indicators that included Radium equivalent (Raeq), air absorbed dose rate (Dγ), effective annual equivalent dose rate (AEDE), indoor and outdoor radiation hazard (H) indices, lifetime cancer risk (ELCR), gonadotropin equivalent dose (AGDE), and ideal level index of gamma rays (Iγ) has been calculated. To verify its deleterious character. On the other hand, the results showed that the rate of heat production values ranged between 0.006-0.0015 µW/m3, which indicates a low rate of heat production and does not affect the temperature of the Earth's crust. Finally, In addition to physicochemical parameters such as PH, dissolved solids TDS, and electrical conductivity Ec. All tested data are within the permissible limit of WHO standards. The results of the current study can be used to provide essential baseline data for future epidemiological investigations and surveillance programs in the areas under study.
Corrosion Inhibition Efficiency Investigation of Yttrium Oxide Nanoparticles Coated on Carbon Steel Alloy
Authors: Hassin Maha J. , Salman Taghried A.
Published: April 2023

Metal oxide nanoparticles demonstrate uniqueness in various technical applications due to their suitable physiochemical properties. In particular, yttrium oxide nanoparticle(Y2O3NPs) is familiar for technical applications because of its higher dielectric constant and thermal stability. It is widely used as a host material for a variety of rare-earth dopants, biological imaging, and photodynamic therapies. In this investigation, yttrium oxide nanoparticles (Y2O3NPs) was used as an ecofriendly corrosion inhibitor through the use of scanning electron microscopy (SEM), Fourier transforms infrared spectroscopy (FT-IR), UV-Visible spectroscopy, X-ray diffraction (XRD), and energy dispersive X-ray spectroscopy(EDX), the physico-chemical characterization of Y2O3NPs was examined. The primary characteristic peak of YOY at 565 cm-1, which indicates the synthesis of nanoparticles, is seen in the FT-IR spectra. The XRD pattern showed that a single phase cubic structure of YONPs with an Ia-3 space group had formed. SEM was used to examine the surface morphology. The composition of Yttrium and oxygen in Y2O3NPs was determined to be 78.74% and 21.26%, respectively, according to the EDX results. The anticorrosive behavior was tested by polarization curve in 18.204% CaCl2 solution at five temperatures in the range 293- 313 K. Various concentrations 0.15 0.26 and 0.37 of N Y2O3NPs coating on the carbon steel surface were applied using the electrophoresis deposition method. The obtained results indicated that Y2O3NPs formed a protective film acts as a physical barrier for the protection of steel alloy. Additionally, corrosion protection efficiency values of 0.26 N Y2O3NPs coating were superior to that of 0.15 and 0.37 N Y2O3NPs coating, respectively.
Ni2+, Pt4+, Pd2+, and Mn2+ Metal ions Complexes with Azo Derived from Quinolin-2-ol and 3-amino-N-(5-methylisoxazol-3-yl) Benzenesulfonamide: Synthesis, Characterization, Thermal Study ,and Antioxidant Activity
Authors: Abdulrazzaq Adhraa Ghazi , Al-Hamdani Abbas Ali Salih
Published: April 2023

Diazotization reaction between quinolin-2-ol and (2-chloro-1-(4-(N-(5-methylisoxazol-3-yl)sulfamoyl)phenyl)-2l4-diazyn-1-ium was carried out resulting in ligand-HL, this in turn reacted with the next metal ions (Ni2+, Pt4+, Pd2+, and Mn2+)  forming stable complexes with unique geometries such as (tetrahedral for both Ni2+ and Mn2+, octahedral for Pt4+ and square planer for Pd2+ ). The creation of such complexes was detected by employing spectroscopic means involving ultraviolet-visible which proved the obtained geometries, fourier transfer proved the formation of azo group and the coordination with metal ion through it. Pyrolysis (TGA & DSC) studies proved the coordination of water residues with metal ions inside the coordination sphere as well as chlorine atoms. Moreover, element micro-analysis and AAS that gave corresponding outcome with theoretically counting outcome.  (1H &13C-NMR) and magnetic quantifications can also indicate the formation of ligand-HL and occurrence of coordination. Antioxidant activities of these compounds were evaluated against (DPPH) radical and were compared to the standard natural antioxidant, ascorbic acid. The findings showed that these compounds exhibit excellent radical scavenging activities
Almost Projective Semimodules
Authors: Aljebory Khitam Sahib , Alhossaini Asaad Mohammed Ali
Published: April 2023

The basis of this paper is to study the concept of almost projective semimodules as a generalization of projective semimodules. Some of its characteristics have been discussed, as well as some results have been generalized from projective semimodules.
Using Transient Modeling to Define the Effects of Heave on Wellsite Operations
Authors: Shipton Peter , Amish Mohamed , Gjerstad Kristian
Published: April 2023

The drilling industry is striving to be more efficient, reducing time, costs, and emissions to provide energy solutions for a more climate-conscious world. Reducing nonproductive time (NPT) and invisible lost time (ILT) by utilizing modeling software to optimize tripping operations is one method to combat this. Additional factors such as sea heave have a significant impact on tripping operations on semisubmersible drilling vessels, which do not show a linear response to increased heave. These vessels have compensation systems, but they are often not in use or not completely accurate. Typical heave experienced in the North Sea is between 0.5 and 3-m amplitude and 10–30-second heave period.

In this study, transient modeling software is used to create a digital twin of the wellbore to safely predict the tripping speed and define the effect heave has on the tripping operations, from causing additional swab and surge pressures when in or out of slips to reducing tripping speed and improving efficiency by reducing mud gelling at connections. To further understand the effect heave has on tripping operations, experimental simulations of varying heave magnitude were completed in wellbore sections of 0°, 30°, 60°, and 90° inclination. Model validation was completed before running simulations. The results indicate that in horizontal holes, low heave magnitudes result in no bit or pressure response. The same cannot be said for vertical wells, which show smooth bit movement and pressure response throughout the heave magnitude spectrum. However, in a horizontal hole when the wave height is of a larger magnitude, sufficient to break wellbore friction, bit displacement is observed to display jerky axial stick and slip movement, and resultant increased swab and surge pressures are shown even when accounting for the reduced pressure fluctuations due to string eccentricity in an inclined wellbore. It is proposed that much of the related mechanical and pressure response is due to the properties of the drilling mud, string elasticity, and the forced frequency of the waves on the natural frequency of the drilling rig and drillstring. It is clear from definitive and experimental simulations that extra care must be taken when the heave is significant to maintain wellbore stability and reduce wellbore pressure cycling.
Genetic analysis of a pedigree with MECP2 duplication syndrome in China
Authors: Zeng Lan , Zhu Hui , Wang Jin , Wang Qi-yan , Pang Ying , Luo Ze-min , Chen Ai , Qin Sheng-fang , Zhu Shu-yao
Published: April 2023

Background: MECP2 duplication syndrome (MDS), a rare X-linked genomic disorder affecting predominantly males, characterized by delayed or absent speech development, severe motor and cognitive impairment and recurrent respiratory infections, is caused by duplication of the chromosomal region located on chromosome Xq28, containing the methyl CpG binding protein-2 (MECP2) gene. MECP2 acts as a transcriptional repressor or activator regulating genes related to nervous system development. The objective of the study adds a clinical description of MDS to include imaging changes consistent with during the fetal period to the neonatal period.
Methods: Conventional G-banding was used to analyze chromosome karyotypes of all pedigree tested. Then, High- throughput sequencing technology, advanced biological information analysis and site validation and pedigree validation were verified by Sanger sequencing.
Results: Chromosome karyotype analysis revealed that one male patient had a chromosome karyotype 46, Y, dup (X) (q27.2q28), High- throughput sequencing technology showed an Xq27.1q28 duplication, with spanned 14.45Mb, duplication encompassed the MECP2 gene. Both the mother and grandmother had karyotype 46, X, dup (X) (q27.2q28), CNV-seq(copy number variation sequencing）analysis of their family members confirmed that they had carried similar duplications, with spanned 15.188Mb, as female carriers of the MECP2 duplication. While the father and uncle of the family members do not carry this area duplication. Sanger validation result was consistent with the CNV-seq analysis.
Conclusion: In this study, a case of developmental delay and recurrent respiratory tract infections as the main symptoms, suspected of MECP2 duplication syndrome male child genetic analysis, clear its causes, explore the correlation of genotype and phenotype, more accurately describe the complete clinical spectrum of MDS, provide the basis for prenatal diagnosis and genetic counselling of familial female carriers.
Hydrogel-chitosan and polylactic acid-polycaprolactone bioengineered scaffolds for reconstruction of mandibular defects: a preclinical in vivo study with assessment of translationally relevant aspects
Authors: Ferrari Marco , Taboni Stefano , Chan Harley HL , Townson Jason , Gualtieri Tommaso , Franz Leonardo , Ruaro Alessandra , Mathews Smitha , Daly Michael J , Douglas Catriona M , Eu Donovan , Sahovaler Axel , Muhanna Nidal , Ventura Manuela , Dey Kamol , Pandini Stefano , Pasini Chiara , Re Federica , Bernardi Simona , Bosio Katia , Mattavelli Davide , Doglietto Francesco , Joshi Shrinidh , Gilbert Ralph W , Nicolai Piero , Viswanathan Sowmya , Sartore Luciana , Russo Domenico , Irish Jonathan C
Published: April 2023

Background Reconstruction of mandibular bone defects is a surgical challenge, and microvascular reconstruction is the current gold standard. The field of tissue bioengineering has been providing an increasing number of alternative strategies for bone reconstruction.Methods In this preclinical study, the performance of two bioengineered scaffolds, an hydrogel made of polyethylene glycol-chitosan (HyCh) and an hybrid core-shell combination of poly(L-lactic acid)/poly(\(\epsilon\)-caprolactone) and HyCh (PLA-PCL-HyCh), seeded with different concentrations of human mesenchymal stem cells (hMSCs) (i.e. 1000, 2000, and 3000 cells/mm3), has been explored in non-critical size mandibular defects in a rabbit model. The bone regenerative properties of the bioengineered scaffolds were analyzed by in vivo radiological examinations and ex vivo radiological, histomorphological, and immunohistochemical analyses.Results The relative density increase (RDI) was significantly more pronounced in defects where a scaffold was placed, particularly if seeded with hMSCs (2000 and 3000 cells/mm3). The immunohistochemical profile showed significantly higher expression of both VEGF-A, in defects reconstructed with a PLA-PCL-HyCh, and osteopontin, in defects reconstructed with both scaffolds. Native microarchitectural characteristics were not demonstrated in any experimental group.Conclusions Herein, we demonstrate that bone regeneration can be boosted by scaffold- and seeded scaffold-reconstruction, achieving, respectively, 50% and 70% restoration of presurgical bone density in 120 days, compared to 40% restoration seen in spontaneous regeneration. Although optimization of the regenerative performance is needed, these results will help to establish a baseline reference for future experiments.
3D-printed near-infrared-light-responsive on-demand drug-delivery scaffold for bone regeneration
Authors: Dong Qinyuan , Wan Zhuqing , Li Qing , Liu Yunsong , Zhang Ping , Zhang Xiao , Niu Yuting , Liu Hao , Lv Longwei , Zhou Yongsheng
Published: April 2023

Background: Although bioactive 3D-printed bone scaffolds loaded with multiple kinds of biomolecules have been developed for enhanced bone regeneration, the manipulation of the on-demand release profiles of different biomolecules during bone regeneration remains challenging.
Method: In this study, we fabricated a 3D-printed dual-drug-loaded biomimetic scaffold. The near-infrared (NIR) light-responsive polydopamine-coated hydroxyapatite nanoparticles were designed to deliver the osteogenic drug, pargyline (PGL). Further, a chemotactic small-molecule drug, simvastatin (SIM), was directly incorporated into the hydroxyapatite/collagen bioink for 3D printing. We then evaluated the morphological, mechanical, photothermal properties of scaffold as well as the in vitro releasing profiles of SIM and PGL. Cell proliferation, adhesion, migration and osteogenic differentiation were investigated. The rabbit cranial defect model was utilized to evaluated the in vivo new bone formation.
Results: Our scaffold displayed an on-demand sequential release of the two drugs, in which the SIM could be rapidly released during the early stage and the PGL could be released in a NIR light-responsive manner. This on-demand releasing profiles could optimize their therapeutic effects to align with the stem cell recruitment and osteoblastic differentiation, thereby promoting bone regeneration. The results confirmed the suitable mechanical strength, high photothermal conversion efficiency, good biocompatibility of our scaffold. The scaffold loaded with SIM could efficiently accelerate the migration of stem cells. In addition, the scaffold with on-demand sequential release promoted alkaline phosphatase (ALP) activity, significantly upregulated gene expression levels of osteogenesis-related markers, and enhanced new-bone-formation capabilities in rabbit cranial defect models.
Conclusion: Our 3D-printed scaffold performs an on-demand delivery of drugs and enhanced bone regeneration. This scaffold not only offers a promising strategy to control the behavior of stem cells during bone regeneration but also provides an efficient strategy for controllable sequential release of different biomolecule in bone tissue engineering.
Biochar increased retention of 15 NH 4 + in a tropical Acrisol under rain-fed maize crop
Authors: Munera-Echeverri J. L. , Martinsen V. , Talmo I.K. , Dörsch P. , Obia A. , Mulder J.
Published: April 2023

Biochar addition has been shown to affect important soil fertility characteristics, including soil pH and soil water retention. Such changes may have pronounced effects on nitrogen (N) cycling. In a field experiment in maize on a sandy loam, we added a small dose of 15N (added as either 15NO3− or 15NH4+), 11 weeks after planting, and traced it during ten days in soil, extractable nitrate, and maize plants. In addition, we assessed the effect of biochar on nitrous oxide (N2O) fluxes. The study was conducted in 20 m2-plots established on a farm in central Zambia, under conservation agriculture without (CA-NORM) and with 4-ton ha− 1 pigeon pea biochar (CA-BC). The results show a positive effect of biochar on soil organic carbon content, soil moisture and extractable NO3−. However, no significant change was observed in soil properties such as pH, cation exchange capacity (CEC) and extractable NH4+, and neither on N2O fluxes nor biomass production. The total recovery of 15N was significantly greater if added as 15NH4+ than as 15NO3− and more than 95% of the 15N in the soil was found in the residual N pool (viz. NH4+ and organic N). The uptake of 15N in aboveground biomass was significantly greater if added as 15NH4+ than as 15NO3−. Compared to CA-NORM, CA-BC increased the recovery of 15N in the soil residual N pool with 46%, 240 hours after addition of 15NH4+. Our results suggest that biochar may reduce losses of NH4+ in Acrisols.
Comparing ambition of EU companies with science-based targets to EU regulation-imposed reductions
Authors: Roelfsema Mark , Kuramochi Takeshi , Elzen Michel Den
Published: April 2023

Companies can support countries in closing the emissions gap between current policies and the Paris goals by implementing pledged voluntary greenhouse gas (GHG) emission reduction targets that are more stringent than the national climate policy regulation requires. For this purpose, we assessed the potential impact of EU companies with 2030 emission reduction targets approved as 2/1.5 °C-consistent by the Science Based Targets initiative (SBTi) in the sectors that are regulated by the Emissions Trading System (ETS) and Effort Sharing Regulation (ESR). To verify potential additionality, company targets were compared to a current policies scenario based on ETS and ESR trends set under the then applicable 40% by 2030 reduction target, and two scenarios that include the voluntary SBTi targets excluding or including flanking measures to materialise additional reductions in ETS. Depending on the assumption of these flanking measures, EU companies with SBTi-approved targets are projected to result in a 4% or 14% reduction by 2030 relative to the EU current policies scenario. Our results illustrate that SBTi-approved companies are not significantly more ambitious than the rest of the emitters in the EU without flanking measures. However, it does show that companies regulated by ETS show higher estimated reductions by 2030 compared to those only regulated by ESR. This analysis shows that more policy detail is important in assessing the additionality of voluntary targets, resulting in zero additional emissions for ETS if a conservative estimate is required.
NDP52 mediates an antiviral response to hepatitis B virus infection through Rab9-dependent lysosomal degradation pathway
Authors: Cui Shuzhi , Xia Tian , Zhao Jianjin , Ren Xiaoyu , Wu Tingtao , Kameni Mireille , Guo Xiaoju , He Li , Guo Jingao , Duperray-Susini Aléria , Levillayer Florence , Collard Jean-Marc , ZHONG JIN , Pan Lifeng , Tangy Frederic , Vidalain Pierre-Olivier , Zhou Dongming , Jiu Yaming , FAURE Mathias , Wei Yu
Published: April 2023

Autophagy receptor NDP52 triggers bacterial autophagy against infection. However, the ability of NDP52 to protect against viral infection has not been established. We show that NDP52 binds to envelop proteins of hepatitis B virus (HBV) and triggers a degradation process that promotes HBV clearance. Inactivating NDP52 in hepatocytes results in decreased targeting of viral envelops in the lysosome and increased levels of viral replication. NDP52 inhibits HBV at both viral entry and late replication stages. In contrast to NDP52-mediated bacterial autophagy, lysosomal degradation of HBV envelops is independent of galectin 8 and ATG5. NDP52 forms complex with Rab9 and viral envelop proteins and links HBV to Rab9-dependent lysosomal degradation pathway. These findings reveal that NDP52 acts as a sensor for HBV infection, which mediates a unique antiviral response to eliminate the virus. This work also suggests direct roles for autophagy receptors in other lysosomal degradation pathways than canonical autophagy.
Adaptive Graphical Routing Methodology for reducing traffic overhead in Wireless Sensor Networks
Authors: c sureshkumar , s sabena , L sairamesh
Published: April 2023

Increasing the scalability and location identification are the prime issues in Wireless Sensor Networks. The Geographical routing is used for getting solution to this kind of issues, but the main disadvantage of Geographical routing is its rely on greedy method and void node problem is the main issue of providing quality of routing. This paper demonstrates the Adaptive Graphical Routing methodology (AGR) for wireless sensor networks. In AGR, the adjacent hop is elected from nodes accessible dynamically with density of the network in some specific angle. The selection of forwarding node within the nodes in a solid angle is computed using the delay aware contention methodology. The proposed AGR methodology will solve the collision problem by prevention of looping and identifying the better path for routing. Moreover, the proposed methodology will utilize the outside of the solid angle using RTS and CTS concepts in dynamic routing. Reducing the traffic overhead by dynamic routing methodology will increase the quality of routing in wireless sensor networks. The performance of the proposed method is compared with the related methods using NS2 simulator. The simulation results specify that AGS achieves an improved packet delivery ratio by increasing the residual energy and reducing the traffic overhead.
Enhancing linkage to HIV care in the “Universal Test-and-Treat” era: Barriers and enablers to HIV care among adults in a high HIV burdened district in KwaZulu-Natal, South Africa
Authors: Nicol Edward , Jama Ngcwalisa Amanda , Mehlomakulu Vuyelwa , Hlongwa Mbuzeleni , Pass Desiree , Basera Wisdom , Bradshaw Debbie
Published: April 2023

Ending AIDS by 2030 would depend on how successful health systems are in linking people living with HIV (PLHIV) into care. The World Health Organization recommended the ‘Universal Test-and-Treat’ (UTT) strategy – initiating all individuals testing positive on antiretroviral therapy (ART) irrespective of their CD4 count and clinical staging. This study aimed to explore the enablers and barriers to linkage to HIV care among adults with a new HIV diagnosis in a high-HIV prevalent rural district in South Africa. A qualitative study was undertaken to explore patients’ perceptions of enablers and barriers of linkage-to-care, using a life-story narration and dialogue approach. In-depth interviews were conducted with 38 HIV-positive participants sampled from a cohort of 1194 HIV positive patients recruited from December 2017 to June 2018. Participants were selected based on whether they had linked to care or not within 3 months of positive HIV diagnosis. Interviews were thematically analysed using a general inductive approach. Of the 38 participants, 22 (58%) linked to care within three months of HIV-positive diagnosis. Factors which facilitated or inhibited linkage-to-care were found at individual, family, community, as well as the health systems levels. Enablers included a positive HIV testing experience, and assistance from the fieldwork team. Support from family, friends, as well as prior community-based education about HIV and ART were also noted. Individual factors such as acceptance of HIV status, previous exposure to PLHIV, and fear of HIV progressing, were identified. Barriers to linkage included, denial of HIV status, dislike of taking pills, and preference for alternative medicine. Negative experience with counselling and health systems inefficiency were also noted as barriers. Perceived stigma and socio-economic factors, such as lack of food or money to visit the clinic were other barriers. Community-based and health system level interventions would need to focus on clinic readiness in providing patients with necessary and effective health services such as proper and adequate counselling. This could increase the number of patients who link to care. Finally, interventions to improve linkage-to-care should consider a holistic approach, including training health care providers, community outreach and the provision of psychological, social, and financial support.
The Effect of War on Educational Institutions of Eastern Tigray Zone, Tigray State, Ethiopia.
Authors: Tekulu . Fikre Belay , Asgedom Desalegn Birhane , Gebre Haftom Teshale , Desta Gebretsadikan Mulubirhan , Shifare Tsigab Hagos , Gebremariam Hagos , Hadigu Tadesse Birhane
Published: April 2023

The objective of this study was to assess the effect of war on school damages in the Eastern Tigrai zone. The study employed both quantitative and qualitative methods, such as questionnaires, interviews, focus group discussions, and observation used for data collection. Simple random sampling was used to select the participants. The study indicated 82.6 percent of the household respondent believes the effect of war on school destruction is high to very high. Based on the field observation of randomly selected schools 57.1 percent and 42.9 percent of schools are severely and completely damaged respectively. The study employed a linear regression model the result depicts statistically significant and war explains 84.6 percent of the observed change in school damage. The destruction of schools resulted in 50.3 percent of students being unable to attend their elementary school and the radius of walking distances to elementary and secondary schools increased from 2.2 km to 4.84 km and 6.3 km to 18.22 km respectively. The destruction of schools has resulted from the total collapse of the educational system in the Eastern Tigrai zone. The study will be helpful for the establishment to take suitable steps in the restoration process.
Prognostic Value and Immunological Role of MMRN1: A Rising Star in Cancer
Authors: Zhou Qing , Liu Ying , Zhang Wenling
Published: April 2023

Background Multimerin 1 (MMRN1) is a factor V binding protein, which could support platelet adhesion and thrombus formation. In recent years, the role of MMRN1 in cancer has begun to attract attention. But systematic studies in this area are lacking. Therefore, we used bioinformatics methods to analyze MMRN1 in tumors to reveal the possible role of MMRN1.Methods Using the Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) database, we obtained relevant data for analyzing MMRN1. Using Gene Expression Profiling Interactive Analysis (GEPIA), Human Protein Atlas (HPA), TCGA, GeneMANIA, and cBioPortal, we explored the potential role of MMRN1 in different types of tumors. Tumor Immune System Interactions and Drug Bank (TISIDB) and Sangerbox were used to analyze the correlation between MMRN1 and tumor immunity. Gene set cancer analysis (GSCA) and UALCAN were used to analyze the methylation of MMRN1. GSCA was also used to analyze the drug sensitivity of MMRN1.Results MMRN1 is down-regulated in most cancer types and is closely related to the prognosis of cancer patients. Interestingly, MMRN1 was found to be positively correlated with immune-related genes in most tumors. In addition, we observed different levels of methylation and mutations in different types of tumors. Drug sensitivity analysis found that MMRN1 was negatively correlated with several drugs, including GW-2580 and TL-1-85, suggesting that it can be used to develop potential anticancer therapies.Conclusion Our analysis demonstrated a significant relationship between MMRN1 and prognosis, tumor immunity, and drug sensitivity of several tumors. As a rising star in cancer, it needs further research.
The Two-dimensional MHD Simulation of The Earth's Magnetosphere
Authors: Filawati Siska , Setiahadi Bambang , Subagyo Bintoro Anang
Published: April 2023

The magnetosphere is the outermost part of the Earth, formed by the interaction of the Earth's dipole magnetic field and the solar wind. Solar wind conditions depend on solar activity, which can affect space weather. One of the solar activities that significantly impact space weather is Coronal Mass Ejection (CME). The magnetosphere is observed using satellites in space-based and using a magnetometer on earth-based. However, these observations are limited to a specific location and time. In this work, we are interested in employing magnetohydrodynamics (MHD) to investigate the interaction of solar wind in the magnetosphere. The MHD has four equations: transfer of mass, momentum, magnetic, and thermal energy, which explain the four main parameters of the solar wind: density, velocity, magnetic field, and pressure, respectively. From these four parameters, the response of Earth's magnetosphere can be identified. Here, we used both analytical and numerical calculation via the SHASTA-FCT. The results show that the positive interplanetary magnetic field merges to Earth's magnetic field. However, the negative interplanetary magnetic field does not merge with Earth's magnetic field. We also observed that the solar wind speed affects the simulation time. The higher the solar wind speed, the shorter the simulation time. The bow shock as a result of the interaction of the solar wind and the Earth's magnetic field is formed at a distance of ∼ 50, 000 km, and the magnetopause as a result of the equilibrium of the solar wind pressure and the pressure of the Earth's magnetic field has a thickness of ∼ 5, 000 km. In addition, we also discuss Alfven's velocity represents the motion of the magnetic field.