bluuebunny/crossref_metadata_2025 huggingface dataset:
Accelerated Homotopy Perturbation Elzaki Transformation Method for Solving Nonlinear Partial Differential Equations
Authors: Jasrotia Shabnam , Singh Prince
Published: June 2022

In this paper, Accelerated Homotopy perturbation Elzaki Transformation Method (AHPETM) is applied to obtained an approximate series solution of the nonlinear partial differential equation. The proposed method was derived by combining accelerated homotopy perturbation method and Elzaki transform. This method is capable of reducing the size of computational work and found to be more efficient method. To support the effectiveness and legitimacy of proposed method, the proposed technique is implemented on nonlinear partial differential equation.
Fuzzy ELECTRE and TOPSIS method to analyze the risk factors of tuberculosis
Authors: Ezhilarasan N. , Felix A.
Published: June 2022

Tuberculosis (TB) is an infectious disease that mainly affects the lungs and it is caused by Mycobacterium tuberculosis bacteria. WHO reported that nearly 1.4 million people died of TB in 2019 and TB is one of the top 10 causes of death in the world. Over 95% of cases and deaths are occurring in developing countries and a lot of factors such as diabetes, immune problem, malnutrition, alcohol, active smoking, crowded places, HIV infection, air pollution, kidney diseases, cancer and tuberculosis treatment workers are linked to TB. So, it is our utmost interest is to analyze the risk factors of TB. Therefore, this present study intended to combine the salient features of ELECTRE and TOPSIS methods under a fuzzy environment to analyze the risk factors of TB. Moreover, the comparative analysis is demonstrated to find the most influencing risk factors of TB. Finally, the sensitivity analysis is also performed using the entropy method to verify the results.
Cost effective light weight concrete with saw dust and brick ballast
Authors: Garg A , Sharma P K
Published: June 2022

Use of conventional material such as cement, sand and gravel for the production of concrete has increased their demand and so created shortage of material and escalated the cost. In this study the locally available waste materials like Saw dust and Brick Ballast are used to partially replace the river sand and gravels respectively to produce light weight and low cost concrete with optimum strength. The different combinations of concrete with 4%, 8% and 12% Saw Dust (SD) and 8%, 16% and 24% Brick Ballast (BB) are being used and compared with normal concrete of M30 grade, where partial replacement of river sand and coarse aggregates are done by saw dust and brick ballast respectively. Concrete is tested for density, workability and compressive strength and a comparative analysis is done in terms of their physical properties and cost savings. It has been observed from the study that on increase in percentage of sawdust and brick ballast in concrete lead to a corresponding reduction in workability and compressive strength. The optimum mix founded is with 4% of sawdust and 24% of Brick ballast having compressive strength of 32.13 N/sq. mm with the weight reduction of 10.54% and the cost reduction of 5.46%. This optimum mix concrete can be used for lean concrete works like PCC in foundation, Flooring, Tile making. This research will not only enrich the domain but will also be very helpful in sustainable development of the nation.
Down conversions excitation dependent luminescent properties of Terbium Aluminum Garnet
Authors: Bala Anu , Rani Suman
Published: June 2022

TAG (terbium aluminum garnet, (Tb3Al5O12) is being investigated recently for their applications in the realization of photonic devices because of its broad transmission ranging from 350 to 1500nm. An emission property of any material depends upon electronic transition levels, temperature, excitation wavelength etc. A lot of research had been reported on temperature dependent emission properties of TAG. In this study an attempt had been made to explore the excitation dependent emission properties of TAG. TAG was prepared by sol gel technique followed by sintering at 1100°C. Structural phase was analysis from the XRD spectra. XRD studies confirmed the formation of nano material and has cubic structure. The emission properties were studied by exciting the TAG by UV light and blue light i.e. 280nm, 300nm, 380 nm, 400nm, 480 and 484nm. Spectra power distribution curve was obtained from emission data excited by with UV radiation and blue light. From emission spectra, Colour co-ordinates (CIE), colour correlated temperature (CCT) and colour purity were calculated for TAG at different excitation. Emission properties indicates that TAG is potential nanophosphor for optical devices.
Acoustic studies of molecular interactions of chlorhexidine with glycols at different temperatures
Authors: Kaur Parminder , Juglan K.C. , Kumar Harsh
Published: June 2022

The Density and Ultrasonic Velocity of chlorhexidine with glycols have been measured at different range of temperatures for different concentrations. Ultrasonic and volumetric data has been used to calculate various parameters such as adiabatic compressibility, acoustic impedance, available volume, molar volume, intermolecular free length, Rao’s constant, Van Der Waal Constant, Wada’s constant, relative intensity, and effective molecular weight. The calculated various parameters suggest solute-solvent interactions occurring in the liquid mixtures. Some other parameters suggest dipole-dipole interactions or formation of complex or charge transfer interactions.
Mo2C-MoS2 heterojunction a suitable and stable electrocatalyst for HER and supercapacitor Applications
Authors: Ahmad Mir Rameez , Upadhyay Sanjay , Kaur Navpreet , Pandey O.P.
Published: June 2022

In the present work, Mo2C-MoS2 heterojunction structures have been prepared by the wet impregnation method. For heterojunction species, the content of MoS2 was varied from 5 to 20% by weight. The effect of the loading content of MoS2 over Mo2C on hydrogen evolution reaction (HER) activity and electrochemical (EC) capacitance performance has been studied in detail. The Mo-C-S junction plays a key role in enhancing the HER activity and EC capacitance performance than the individual components. The prepared structures show enhanced HER activity with high current density ~36.2-78.3 mAcm-2 at very low applied potential (0.45 V), exhibiting a lower Tafel slope of 102.4 mVdec-1. The EC capacitor performance determined by CV and galvanic charge-discharge (GCD) reveals that the synthesized samples exhibit an electrochemical double-layer capacitor (EDLC, Cdl) behavior. The higher EDLC (43.9 mFcm-2) and specific capacitance (2Fg-1) obtained for the synthesized samples determine their potential applicability for the new generation supercapacitors.
Propagation of SH-waves in two layered piezoelectric/fiber-reinforced composite plate
Authors: Singh Kulwinder , Sawhney Shruti , Pathania D.S
Published: June 2022

This article deals with the study of propagation of shears waves in a composite structure consisting of a piezoelectric layer superimposed on a layer of fiber-reinforced material. A mathematical model is framed and the dispersion relation of shear wave is derived analytically. By suitable substitutions the dispersion relation obtained is reduced to the well-known classical Love wave equation. The effects of various parameters such as wave number, thickness ratio and the direction of fiber-reinforced parameters on the shears wave velocity has been investigated and depicted graphically.
A mini-review on rare earth metal doped ZnO nanomaterials for photocatalytic remediation of waste water
Authors: Kumar Ripan , Dosanjh H S
Published: June 2022

The mineralization and degradation of organic compounds present in waste water by heterogeneous photocatalysis has gained wide attention due to its effectiveness and tenancy to utilize UV-Visible solar light spectrum. The chemical stability, non-toxic character, magnificent electrical and optical properties have been recognized the ZnO as useful material for waste water treatment in environmental remediation technology. However, photocatalytic activity of ZnO limited to ultraviolet region because of its wide band gap (3.37eV). ZnO wide band gap obstruct photo-excitation for actual photocatalytic applications under abundant, safe and clean solar energy source. Many methods have been evolved in last decades to overcome this barrier. ZnO surfaces have been tailored with rare-earth metals to enhance its optical, surface and photocatalytic properties by different research groups. The doping with rare-earth metal ions enhanced the efficiency of ZnO photocatalyst by reducing band gap and shifted the absorbed wavelength to the visible region. This review paper compiles the attempts on modification of ZnO and their effect on photocatalytic activities by using rare earth metals.
Machine learning based computer aided diagnosis system for classification of breast masses in mammograms
Authors: Singh Harmandeep , Sharma Vipul , Singh Damanpreet
Published: June 2022

Breast cancer continues to be the most common cancer in the fastest developing and the developed nations. Early detection by using mammography has been proven as the best prognosis. Computer Aided Diagnosis (CAD) systems are being used as second reader for the analysis and interpretation of mammogram images. In the last two decades, although breast cancer incidence has increased by many folds but unfortunately the progress in this field has almost stagnated. Therefore, the CAD systems need to be improved to be considered useful. In this study, a machine learning based CAD system for segmentation and classification of breast masses have been proposed. The IRMA Version of DDSM dataset has been used for experimentation and evaluation of the proposed system. Exact breast masses were segmented from manually extracted ROIs of 700*700 pixels by employing an improved seeded region growing algorithm. Various geometry and texture features were computed from the segmented mass lesions and corresponding ROIs respectively. The classification performances of nine state-of-the-art classifiers namely K-Nearest Neighbour (KNN), Support Vector Machine (SVM), Gaussian Mixture Model (GMM), Multi-class Support Vector Machine (mSVM), Decision Tree (DT), Discriminate Analysis (DA), Naive Bayes (NB), Random Forest (RF), Ensemble Tree (ET) have been investigated in this study. On evaluating the experimental results for all the classifiers, highest classification accuracy is obtained with SVM classifier. The experimental results reveal that the proposed improved seeded region growing approach has been proven helpful in improving the classification performance of the proposed system.
Advancement of Gate Oxides from SiO2 to High-k Dielectrics in Microprocessor and Memory
Authors: Sharma U. , Kumar G. , Mishra S. , Thomas R.
Published: June 2022

Silicon and its native oxides (SiO2) have led the continuous development in the integrated circuits for decades. The excellent insulating properties of SiO2 and silicon/SiO2 interface quality were used as capacitor dielectrics in random-access memories (RAM’s) and transistor gate dielectrics in complementary metal-oxide semiconductor (CMOS’s), respectively, for the memory and logic devices. These are the core components and act as the heart of the semiconductor industry. However, reducing the thickness of SiO2 to increase the capacitance at a reduced lateral size resulted into high leakage current and large power consumption in the aforementioned high-density semiconductor devices. To overcome this concern, high-permittivity materials were considered in replacing the SiO2 to achieve high capacitance at a higher thickness. Numerous materials ranging from Al2O3 (k~9) to perovskites (k~102-104) are being actively investigated but Hafnium based compound high-k dielectric/metal gate (k~10-15) captivate great attention and used for logic and memory devices. However, finding a real high-k material (k~25-40) with silicon is a major challenge by itself as it requires an ideal interface with minimum defects. Therefore, with this article, we review the efforts in replacing SiO2 with higher-k dielectrics over the years to match the performance of processor from generation to generation.
Design of Hybrid Counter using Adiabatic Quantum Flux Parametron
Authors: Narendran S
Published: June 2022

Power consumption is one of the most considered factors while designing any electronics digital circuit. In which, the Adiabatic Quantum Flux parametron (AQFP) is one of the best superconducting technology for reduced power factor. Adiabatic Quantum Flux Parametron (AQFP) will be powered by the use of AC (Alternating Current) in place of DC power supply. In this research article, a hybrid counter is designed based on Adiabatic Quantum Flux Parametron (AQFP). The hybrid counter is modelled using parallel counter circuits. This counter is designed based on different stages of manipulation. The different stages are based on the number of bits used in the design. Here the design is made up of 4 - bit hybrid counter with four stages of computation and due to these stages of computation, the computation cost is reduced up to 28% compared to existing semiconductor counter electronics circuits. Since the computation cost is reduced, which directly implies that the speed of design is high speed and power is also reduced in huge factors in range of nanowatts.
Prime labeling of 3-shadow graph of some star related graphs
Authors: Annamma V , Begum N Hameeda
Published: June 2022

A graph G = (V(G), E (G)) is observed to admit prime labeling when the vertices of the graph are labeled with unique integral values from [1,|V|] in a way that for every edge uυ the labels designated to u and υ share no common positive factors except 1. In this research article we investigate that the 3-shadow graphs of some star related graphs such as K
1,n
, B (n, n) and Spl(K
1,n
) admits prime labeling.
Application of Urea Formaldehyde Raisin in Pavement Subgrade Stabilization at Hindon Barrage
Authors: Bansal V , Shukla B K
Published: June 2022

Proper stabilization of foundation and subgrade is one of the major concerns in modern civil engineering projects. Development of modern infrastructure is causing harmful effect on environment by using chemicals. This situation has caused necessity to discover alternative techniques to achieve desired result without harming environment. Present paper studies use of urea formaldehyde raisin on chemical and physical stability of subgrade. Study was conducted by varying contents of urea formaldehyde by 1%, 3% and 5% and strength, ultimate bearing capacity and other relevant soil strength parameters were determined. At the end, cost benefits analysis was also conducted for the current method with respect to alternate subgrade stabilization techniques.
Investigation for the numerical solution of Klein-Gordon equations using scale 3 Haar wavelets
Authors: Kumar Ratesh
Published: June 2022

In this article, a new numerical technique based upon Haar scale 3 wavelets is proposed for the solution of Klein-Gordon equations. Klein-Gordon equation occurs in many phenomena of applied physics such as quantum field theory, fluid dynamics, etc. Wavelets have become a powerful tool in almost all areas of engineering and science. Therefore, in this technique, spatial discretization is done by Haar scale 3 Wavelets. The collocation method is used with Haar scale 3 wavelets to convert Klein-Gordon equation into the system of algebraic equations. To deal with the non-linearities in equations, the quasilinearization process is used. The proposed scheme is tested on three test problems of the above-said types, and the proposed scheme’s competency is established.
Properties Of 2-Fibonacci Sequence
Authors: Verma Vipin , Priyanka
Published: June 2022

In this paper, properties of 2-Fibonacci sequence {Cn
} defined by C

n+4 = C

n+2 + 2C

n+1 + Cn
are developed and proved in the form of closed forms of the summation formulas. Also, the closed form of summation formulas of its square has been proved. In particular, the properties involving alternating sum of 2-Fibonacci sequence and product of 2-Fibonacci terms having different indices are discussed. We present the proofs to indicate how these formulas, in general, were developed. Of course, all the listed properties are proved by induction.
Doxycycline Treatment of Mansonella perstans–Infected Individuals Affects Immune Cell Activation and Causes Long-term T-cell Polarization
Authors: Aniagyei Wilfred , Adjei Jonathan Kofi , Adankwah Ernest , Seyfarth Julia , Mayatepek Ertan , Antwi Berko Daniel , Sakyi Samuel Asamoah , Batsa Debrah Linda , Debrah Alexander Yaw , Hoerauf Achim , Owusu Dorcas O , Phillips Richard O , Jacobsen Marc
Published: June 2022

Background

Doxycycline is used for treatment of Mansonella perstans infection. Immune modulatory effects of both M. perstans and doxycycline have been described but long-term implications on host immune response are not defined. Here we determined multiple immune parameters of M. perstans–infected individuals before and after doxycycline treatment to characterize doxycycline effects on host T-cell immunity.

Methods

Immune characterization of doxycycline-treated M. perstans–infected individuals was performed as part of an open-label randomized clinical trial. Immune cell population phenotyping by flow cytometry and functional in vitro T-cell assays were performed at baseline, 6 months, and “long term” (18–24 months) after treatment start. Treatment efficacy, based on peripheral blood microfilaria (mf) burden, was correlated with immune parameters and effects on immune response against concomitant Mycobacterium tuberculosis infection were determined.

Results

Immune population phenotyping indicated changes in functional T-cell responses after doxycycline treatment. Constitutive and superantigen-induced T-cell activation and polarization towards T-helper type (TH) 1 phenotype at baseline declined after doxycycline treatment, whereas low proportions of TH17 and TH1* cells at baseline increased significantly at follow-up. In accordance, long-term decline in antigen-specific TH1 responses against concomitant M. tuberculosis infection was seen. Notably, only TH17 and TH1* changes after 6 months and TH17 at baseline were negatively correlated with M. perstans microfilaria burden or reduction, whereas long-term changes were not associated with treatment efficacy.

Conclusions

We found long-term immune modulatory effects of doxycycline treatment leading to decreased constitutive T-cell activation, polarization towards TH17/TH1*, and impaired immune response against concomitant M. tuberculosis infection.
Who Should Get Vaccinated First? Limits of Solidarity during the First Week of the Danish Vaccination Programme
Authors: Schaeffer Merlin , Haderup Larsen Mikkel
Published: June 2022

The coronavirus disease 2019 (COVID-19) pandemic resulted in several acute shortages of healthcare provision and thereby posed a challenge to solidarity among citizens of welfare states. One example was the limited number of vaccine batches at the outset of European COVID-19 vaccination campaigns. This resulted in a rare constellation in which citizens faced both a unifying collective threat but also a scarcity of healthcare resources that necessitated the prioritization of certain groups for an early vaccination. On that premise, we conducted a survey experiment during the first week of the Danish vaccination programme. Our results demonstrate that citizens judged who deserves early access to preventive healthcare along established lines of welfare chauvinism. Fictitious diabetes patients with a Muslim name and those who recently immigrated were regarded as less deserving of an early vaccination. That said, concerns over responsibility for one’s hardship and anti-social free-rider behaviour drive citizens considerations, too. Contra our hypotheses, we find only weak evidence that immigrants or Muslims are penalized more harshly for an irresponsible lifestyle or free-rider behaviour. Compared with previous research, we study a unique moment in history and are the first to disentangle minority status from stereotypes about their anti-social free-riding behaviour and irresponsibly unhealthy lifestyles.
Production of nascent ribosome precursors within the nucleolar microenvironment of Saccharomyces cerevisiae
Authors: Lin Samantha , Rajan Suchita , Lemberg Sofia , Altawil Mark , Anderson Katherine , Bryant Ruth , Cappeta Sebastian , Chin Brandon , Hamdan Isabella , Hamer Annelise , Hyzny Rachel , Karp Andrew , Lee Daniel , Lim Alexandria , Nayak Medha , Palaniappan Vishnu , Park Soomin , Satishkumar Sarika , Seth Anika , Sri Dasari Uva , Toppari Emili , Vyas Ayush , Walker Julianne , Weston Evan , Zafar Atif , Zielke Cecelia , Mahabeleshwar Ganapati H , Tartakoff Alan M
Published: June 2022

35S rRNA transcripts include a 5′-external transcribed spacer followed by rRNAs of the small and large ribosomal subunits. Their processing yields massive precursors that include dozens of assembly factor proteins. In Saccharomyces cerevisiae, nucleolar assembly factors form 2 coaxial layers/volumes around ribosomal DNA. Most of these factors are cyclically recruited from a latent state to an operative state, and are extensively conserved. The layers match, at least approximately, known subcompartments found in higher eukaryotic cells. ∼80% of assembly factors are essential. The number of copies of these assembly factors is comparable to the number of nascent transcripts. Moreover, they exhibit “isoelectric balance,” with RNA-binding candidate “nucleator” assembly factors being notably basic. The physical properties of pre-small subunit and pre-large subunit assembly factors are similar, as are their 19 motif signatures detected by hierarchical clustering, unlike motif signatures of the 5′-external transcribed spacer rRNP. Additionally, many assembly factors lack shared motifs. Taken together with the progression of rRNP composition during subunit maturation, and the realization that the ribosomal DNA cable is initially bathed in a subunit-nonspecific assembly factor reservoir/microenvironment, we propose a “3-step subdomain assembly model”: Step (1): predominantly basic assembly factors sequentially nucleate sites along nascent rRNA; Step (2): the resulting rRNPs recruit numerous less basic assembly factors along with notably basic ribosomal proteins; Step (3): rRNPs in nearby subdomains consolidate. Cleavages of rRNA then promote release of rRNPs to the nucleoplasm, likely facilitated by the persistence of assembly factors that were already associated with nucleolar precursors.
The bHLH transcription factor AcB2 regulates anthocyanin biosynthesis in onion (Allium cepa L.)
Authors: Li Xiaojie , Cao Linjiao , Jiao Bangbang , Yang Haifeng , Ma Changsheng , Liang Yi
Published: June 2022

Onion bulb color is a key breeding trait. The red bulb color is caused by the presence of anthocyanins, which are products of the flavonoid synthesis pathway. Research on flavonoid regulation in onion is lagging compared with that in other crops. AcB2 encodes a bHLH transcription factor, and its transcription is positively associated with anthocyanin accumulation and correlated with the expression of AcMYB1, which is an activator in the flavonoid biosynthetic pathway in onion. Phylogenetic analysis showed that AcB2 was grouped into the TRANSPARENT TESTA 8 (TT8) clade of the bHLH IIIf subgroup. The AcB2 protein contained an MYB-interacting region and physically interacted with AcMYB1 in yeast and tobacco leaves. AcMYB1 directly bound to the promoters of anthocyanidin synthase (AcANS) and flavonoid 3-hydroxylase 1 (AcF3H1) and activated their expression. The coexpression of AcB2 with AcMYB1 in Arabidopsis thaliana protoplasts dramatically increased the expression of AcANS and AcF3H1 compared with that under the expression of AcMYB1 alone. Transient co-overexpression of AcB2 with AcMYB1 induced anthocyanin accumulation in the epithelial cells of onion bulbs. Complementation of the Arabidopsis tt8-1 mutant with AcB2 restored pigmentation defects in tt8-1. In addition, AcB2 physically interacted with AtTT2 in yeast cells and tobacco leaves, indicating that the functions of AcB2 were similar to those of AtTT8. Together, these results demonstrated that AcB2 enhanced the function of AcMYB1 in upregulating anthocyanin biosynthesis in onion, which provided a theoretical basis for breeding onions with higher anthocyanin contents.
Neighbourhood socioeconomic improvement, residential mobility and premature death: a population-based cohort study and inverse probability of treatment weighting analysis
Authors: Buajitti Emmalin , Rosella Laura C
Published: June 2022

Background

Causal inference using area-level socioeconomic measures is challenging due to risks of residual confounding and imprecise specification of the neighbourhood-level social exposure. By using multi-linked longitudinal data to address these common limitations, our study aimed to identify protective effects of neighbourhood socioeconomic improvement on premature mortality risk.

Methods

We used data from the Canadian Community Health Survey, linked to health administrative data, including longitudinal residential history. Individuals aged 25–69, living in low-socioeconomic status (SES) areas at survey date (n = 8335), were followed up for neighbourhood socioeconomic improvement within 5 years. We captured premature mortality (death before age 75) until 2016. We estimated protective effects of neighbourhood socioeconomic improvement exposures using Cox proportional hazards models. Stabilized inverse probability of treatment weights (IPTW) were used to account for confounding by baseline health, social and behavioural characteristics. Separate analyses were carried out for three exposure specifications: any improvement, improvement by residential mobility (i.e. movers) or improvement in place (non-movers).

Results

Overall, 36.9% of the study cohort experienced neighbourhood socioeconomic improvement either by residential mobility or improvement in place. There were noted differences in baseline health status, demographics and individual SES between exposure groups. IPTW survival models showed a modest protective effect on premature mortality risk of socioeconomic improvement overall (HR = 0.86; 95% CI 0.63, 1.18). Effects were stronger for improvement in place (HR = 0.67; 95% CI 0.48, 0.93) than for improvement by residential mobility (HR = 1.07, 95% 0.67, 1.51).

Conclusions

Our study provides robust evidence that specific neighbourhood socioeconomic improvement exposures are important for determining mortality risks.
Clustered Mendelian randomization analyses identify distinct and opposing pathways in the association between genetically influenced insulin-like growth factor-1 and type 2 diabetes mellitus
Authors: Wang Wenyi , Tesfay Ephrem Baraki , van Klinken Jan Bert , Willems van Dijk Ko , Bartke Andrzej , van Heemst Diana , Noordam Raymond
Published: June 2022

Background

There is inconsistent evidence for the causal role of serum insulin-like growth factor-1 (IGF-1) concentration in the pathogenesis of human age-related diseases such as type 2 diabetes (T2D). Here, we investigated the association between IGF-1 and T2D using (clustered) Mendelian randomization (MR) analyses in the UK Biobank.

Methods

We conducted Cox proportional hazard analyses in 451 232 European-ancestry individuals of the UK Biobank (55.3% women, mean age at recruitment 56.6 years), among which 13 247 individuals developed type 2 diabetes during up to 12 years of follow-up. In addition, we conducted two-sample MR analyses based on independent single nucleotide polymorphisms (SNPs) associated with IGF-1. Given the heterogeneity between the MR effect estimates of individual instruments (P-value for Q statistic = 4.03e−145), we also conducted clustered MR analyses. Biological pathway analyses of the identified clusters were performed by over-representation analyses.

Results

In the Cox proportional hazard models, with IGF-1 concentrations stratified in quintiles, we observed that participants in the lowest quintile had the highest relative risk of type 2 diabetes [hazard ratio (HR): 1.31; 95% CI: 1.23–1.39). In contrast, in the two-sample MR analyses, higher genetically influenced IGF-1 was associated with a higher risk of type 2 diabetes. Based on the heterogeneous distribution of MR effect estimates of individual instruments, six clusters of genetically determined IGF-1 associated either with a lower or a higher risk of type 2 diabetes were identified. The main clusters in which a higher IGF-1 was associated with a lower risk of type 2 diabetes consisted of instruments mapping to genes in the growth hormone signalling pathway, whereas the main clusters in which a higher IGF-1 was associated with a higher risk of type 2 diabetes consisted of instruments mapping to genes in pathways related to amino acid metabolism and genomic integrity.

Conclusions

The IGF-1-associated SNPs used as genetic instruments in MR analyses showed a heterogeneous distribution of MR effect estimates on the risk of type 2 diabetes. This was likely explained by differences in the underlying molecular pathways that increase IGF-1 concentration and differentially mediate the effects of IGF-1 on type 2 diabetes.
On Orthogonal Local Models of Hodge Type
Authors: Zachos Ioannis
Published: June 2022

We study local models that describe the singularities of Shimura varieties of non-PEL type for orthogonal groups at primes where the level subgroup is given by the stabilizer of a single lattice. In particular, we use the Pappas–Zhu construction and we give explicit equations that describe an open subset around the “worst” point of orthogonal local models given by a single lattice. These equations display the affine chart of the local model as a hypersurface in a determinantal scheme. Using this, we prove that the special fiber of the local model is reduced and Cohen–Macaulay.
3D anisotropic TEM modeling with loop source using model reduction method
Authors: Lu Kailiang , Fan Ya'nan , Zhou Jianmei , Li Xiu , Li He , Fan Kerui
Published: June 2022

For model reduction techniques, there have been relatively few studies performed regarding the forward modeling of anisotropic media in comparison to transient electromagnetic (TEM) forward modeling of isotropic media. The transient electromagnetic method (TEM) responses after the current has been turned off can be represented as a homogeneous ordinary differential equation (ODE) with an initial value, and the ODE can be solved using a matrix exponential function. However, the order of the matrix exponential function is large and solving it directly is challenging, thus this study employs the Shift-and-Invert (SAI-Krylov) subspace algorithm. The SAI-Krylov subspace technique is classified as a single-pole approach compared to the multi-pole rational Krylov subspace approach. It only takes one LU factorization of the coefficient matrix, along with hundreds of backward substitutions. The research in this paper shows that the anisotropic medium has little effect on the optimal shift ${\gamma _{opt}}$ and subspace order m. Furthermore, as compared to the mimetic finite volume method (SAI-MFV) of the SAI-Krylov subspace technique, the method proposed in this paper (SAI-FEM) can further improve the computing efficiency by roughly 13%. In contrast to the standard implicit time step iterative technique, the SAI-FEM method does not require discretization in time, and the TEM response at any moment within the off-time period can be easily computed. Next, the accuracy of the SAI-FEM algorithm was verified by 1D solutions for an anisotropic layer model and a 3D anisotropic model. Finally, the electromagnetic characteristics of the anisotropic anomalous body of the center loop device and separated device of the airborne transient electromagnetic method were analyzed, and it was found that horizontal conductivity has a considerable influence on the TEM response of the anisotropic medium.
Born approximation imaging technique for electrical source multi-component TEM
Authors: Fan Ya'nan , Lu Kailiang , Li Xiu , Qi Zhipeng
Published: June 2022

In this study, to obtain higher-resolution geoinformation in the electrical source transient electromagnetic method (TEM) interpretation, the pseudo-seismic Born approximation imaging method is applied to the vertical magnetic induction intensity ${B_z}$ and the horizontal electric field ${E_y}$, which is paralleled to the source. First, the differences between the two components are compared, and the results reveal that different components can reflect varied geological information. ${E_y}$ has a stronger signal and is more sensitive to the high-resistivity layer at a long offset, whereas ${B_z}$ has a greater relative difference in the low-resistivity layer at a short offset. The TEM field is then transformed into the pseudo-wavefield using the wavefield transformation method and the Born approximation pseudo-seismic imaging method is adopted to locate the electrical interface. After calculating the 3D model, the results indicate that the multi-component Born approximate imaging can intuitively and effectively locate the depth of the geological interface. Furthermore, the imaging results of a coal mine located in Gansu Province, China, proves that the proposed method can pinpoint the buried location of the coal goaf as well as the stratum trend. In general, the multi-component pseudo-seismic imaging technique plays a significant role in interpreting the electrical source TEM data.
Noncanonical prokaryotic X family DNA polymerases lack polymerase activity and act as exonucleases
Authors: Prostova Maria , Shilkin Evgeniy , Kulikova Alexandra A , Makarova Alena , Ryazansky Sergei , Kulbachinskiy Andrey
Published: June 2022

The X family polymerases (PolXs) are specialized DNA polymerases that are found in all domains of life. While the main representatives of eukaryotic PolXs, which have dedicated functions in DNA repair, were studied in much detail, the functions and diversity of prokaryotic PolXs have remained largely unexplored. Here, by combining a comprehensive bioinformatic analysis of prokaryotic PolXs and biochemical experiments involving selected recombinant enzymes, we reveal a previously unrecognized group of PolXs that seem to be lacking DNA polymerase activity. The noncanonical PolXs contain substitutions of the key catalytic residues and deletions in their polymerase and dNTP binding sites in the palm and fingers domains, but contain functional nuclease domains, similar to canonical PolXs. We demonstrate that representative noncanonical PolXs from the Deinococcus genus are indeed inactive as DNA polymerases but are highly efficient as 3′-5′ exonucleases. We show that both canonical and noncanonical PolXs are often encoded together with the components of the non-homologous end joining pathway and may therefore participate in double-strand break repair, suggesting an evolutionary conservation of this PolX function. This is a remarkable example of polymerases that have lost their main polymerase activity, but retain accessory functions in DNA processing and repair.
ATRT-03. Adapted Treatment Protocol: Synchronous Atypical Teratoid/Rhabdoid CNS Tumor and Extra CNS Disease
Authors: Jackson Nicole , Torres Marleni , Lecea Eva Glenn , O’Farrell Candelaria , Khatib Ziad , Maher Ossama
Published: June 2022

Atypical teratoid/rhabdoid tumors (AT/RTs) of the central nervous system (CNS) are rare, aggressive, early childhood tumors with unfavorable prognosis. There have been 31 cases reported of children with AT/RT of the CNS and extra CNS primary tumors. In addition to its aggressive tendencies, malignant rhabdoid tumors (MRTs) of the kidney have also shown a common genetic abnormality-inactivating mutation of SMARC B1/INI-gene. We report a 22-month-old male who presented at 15 months of age with metastatic AT/RT of the posterior fossa and synchronous malignant rhabdoid tumor of the left kidney. MRI of the brain demonstrated a midline posterior fossa mass and left renal mass was noted incidentally on imaging of spine. Pathology was consistent with MRT of the kidney and pathogenic variant was found in the tumor sample, specifically SMARCB1 homozygous/biallelic deletion. Patient underwent a subtotal resection of the posterior fossa tumor and subsequent radical resection of the mass on kidney rhabdoid tumor. He was treated as per ACNS033 protocol with 2 cycles of induction with high-dose methotrexate followed by vincristine, cyclophosphamide, cisplatin, and etoposide with complete response followed by three tandem stem cell transplants with thiotepa and carboplatin for which he has been tolerating and responding favorably. Focal radiation therapy to the brain and flank area is planned at end of therapy. In a large series of synchronous AT/RTs reported in 2017 only 3 of the 31 patients were considered long-term survivors. All received a combination of high dose intrathecal or intravenous chemotherapy, total resection of at least one of the tumors, focal radiation, and autologous peripheral blood stem cell transplant. We demonstrated a case with a favorable response with our treatment. Treatment continues to be challenging given the tumor’s rarity and mortality as there are no standardized protocols or randomized controlled trials.
ATRT-07. Low-grade diffusely infiltrative tumor, SMARCB1-mutant: a clinical and histopathological distinct entity showing epigenetic similarity with ATRT-MYC
Authors: Thomas Christian , Federico Aniello , Bens Susanne , Hellström Mats , Casar-Borota Olivera , Kordes Uwe , Neumann Julia E , Dottermusch Matthias , Rodriguez Fausto E , Lo Andrea C , Cheng Sylvia , Hendson Glenda , Hukin Juliette , Hartmann Christian , Koch Arend , Capper David , Siebert Reiner , Paulus Werner , Nemes Karolina , Johann Pascal D , Frühwald Michael C , Kool Marcel , Hasselblatt Martin
Published: June 2022

Most atypical teratoid/rhabdoid tumors (ATRTs) occur in infants, but children and adolescents may also be affected. ATRTs occurring in older patients often comprise the molecular subgroup ATRT-MYC. Recently, central nervous system low-grade diffusely infiltrative tumor with INI1 deficiency (CNS LGDIT-INI1) has been described as a rare low-grade lesion (Nobusawa et al. Am J Surg Pathol 2020;44:1459-1468). Little is known on the molecular relationship of CNS LGDIT-INI1 and ATRT. We therefore further explored a series of six CNS LGDIT-INI1. The median age of the four males and two females was 16 years (range: 10-28 years). All tumors were of supratentorial location and showed low to moderate cellularity, diffuse growth of inconspicuous small SMARCB1-deficient tumor cells and reactive pleomorphic neuronal and glial cells with retained SMARCB1-staining in the background. In addition, two cases also displayed a high-grade rhabdoid component. After DNA isolation, purification and bisulfite conversion, samples were subjected to DNA methylation profiling (MethylationEPIC BeadChip array). Using DNA methylation-based classification and the Heidelberg Brain Tumor Classifier (version v11b4), all tumors were classified as ATRT-MYC (median calibrated score: 0.97). On t-SNE analysis, DNA methylation profiles grouped closely together in proximity to ATRT-MYC. Follow-up information was available for four cases (including the two cases with a high-grade component). Patients received heterogeneous treatments (including chemotherapy according to AT/RT protocols) and experienced stable disease or complete remission after an observation time of three to 56 months. In conclusion, CNS LGDIT-INI1 is a clinically and histologically distinct entity with relatively favorable outcome. Nevertheless, epigenetic similarity with ATRT-MYC and the potential of malignant progression warrants close follow-up examinations. In line with recent developments of WHO nomenclature, we propose to refer to these tumors as “low-grade diffusely infiltrative tumor, SMARCB1-mutant”.
ATRT-11. Anatomico-biological correlations define a new layer for ATRT molecular subgroups pointing to potential lineages of origin
Authors: Lobon-Iglesias Maria , Andrianteranagna Mamy , Han Zhi-Yan , Masliah-Planchon Julien , Tauziede-Espariat Arnault , Frah Magali , Dufour Christelle , Chauvin Celine , Bouarich Rachida , Manriquez Valeria , Turczinski Sandrina , Delattre Olivier , Baulande Sylvain , Ayrault Olivier , Servant Nicolas , Beccaria Kevin , Dangouloff-Ros Volodia , Bourdeaut Franck
Published: June 2022

Atypical teratoid rhabdoid tumors (ATRT) are divided in three molecular subgroups, the so-called MYC, TYR and SHH subgroups. This heterogeneity suggests some diversity in the cells of origin, which remain hypothetical thus far. A careful radiological review of 55 MRI at diagnosis was performed in parallel with a careful analysis of mouse tumor origin in the Rosa26-CreERT2::Smarcbflox/flox model. Methylation, bulk RNAseq and scRNAseq analyses were integrated to these anatomic information to highlight potential origin for each molecularly and anatomically defined subgroups. We demonstrated that mouse Myc-ATRTs derive from extra-parenchymal meningeal areas, a finding consistant with many human MYC ATRT being clearly of intra-cranial extra-axial origin. Although this finding could point to a neural crest origin, transcriptomic features fail to unravel any lineage-specific signature. We also defined a distinct supra-tentorial SHH ATRT subgroup, characterized both in mouse and Humans by neural features pointing to the ganglionic eminence progenitors as the candidate origin. Finally we identified a distinct infra-tentorial SHH ATRT subgroup, not observed in mice, with hindbrain/midbrain boundary progenitor signature. scRNAseq from human SHH infra-tentorial tumors consistently suggest a dedifferentiation process involving the Notch pathway in the oncogenic transformation of hindbrain/midbrain neural progenitors.
ATRT-14. Malignant rhabdoid tumors of cranial nerves – ATRT or extracranial rhabdoid tumor?
Authors: Gruhle Miriam , Nemes Karolina , Steinbügl Mona , Johann Pascal D , von Luettichau Irene , Steinborn Marc , Tippelt Stephan , Fleischhack Gudrun , Lehrnbecher Thomas , Bens Susanne , Siebert Reiner , Hasselblatt Martin , Vokuhl Christian , Bison Brigitte , Kröncke Thomas , Melchior Patrick , Timmermann Beate , Frühwald Michael C
Published: June 2022

INTRODUCTION: Malignant rhabdoid tumors (MRT) are highly aggressive neoplasias mostly affecting young children. They are classified as rhabdoid tumors of the central nervous system (ATRT, atypical teratoid rhabdoid tumor), rhabdoid tumors of the kidney (RTK) or extracranial rhabdoid tumors arising from any soft tissue outside the central nervous system (eMRT, extracranial extrarenal MRT). We report a series of four MRTs with cranial nerve involvement. METHODS: Patients were identified from a cohort of 132 patients with MRT (2017 – 2021), as part of the European Rhabdoid Registry (EU-RHAB). Diagnosis of MRT was confirmed immunohistochemically with loss of INI1 expression. Details regarding symptoms at first presentation, diagnostic staging, genetic findings, therapy and the course of disease are reported. REPORT OF CASES/RESULTS: The series contains two MRT affecting the trigeminal nerve and two cases with third cranial nerve involvement. They were two female and two male patients with a median age of 4.7 years (1-159 months) at diagnosis. Location of the main tumor mass differed between being located intra- and extracerebrally. Metastases at diagnosis occurred in one patient, a germ-line mutation in SMARCB1 was present in two patients. Two patients received therapy according to EU-RHAB recommendations with an incomplete resection, conventional chemotherapy enhanced by intraventricular methotrexate and radiotherapy. Both patients are currently alive with no signs of progression, one of them bearing a germ-line mutation. Two patients received palliative treatment after surgery due to rapid progression. Median overall survival was 17.3 (1.4-53.1) months. CONCLUSION: MRT of the cranial nerves affect the peripheral nervous system in close proximity to the brain, thus forming a unique sub-entity between ATRT and eMRT. The selected cases provide insight into the particular challenge regarding clear classification, diagnostics and therapy.
ATRT-16. Mechanisms of myeloid cell-induced resistance in AT/RT
Authors: Disch Alina , Melcher Viktoria , Walter Carolin , Interlandi Marta , Moreno Natalia , de Faria Flavia W , Graf Monika , Hasselblatt Martin , Albert Thomas K , Kerl Kornelius
Published: June 2022

INTRODUCTION: Atypical teratoid/rhabdoid tumor (AT/RT) is a primary pediatric tumor entity of the central nervous system showing intra- and intertumoral heterogeneity concerning the molecular landscape and cellular composition. Myeloid cells are considered key orchestrators of the immunological tumor microenvironment (TME) of AT/RT. Tumor-infiltrating CD68+ macrophages favor chemotherapy resistance and recurrence, and are consequently related to a poor patient outcome. METHODS: Using single-cell RNA sequencing (scRNA-seq) of human and murine AT/RT samples, multiplex immunohistochemistry, depletion of myeloid cells in mouse models and advanced cell culture models for myeloid tumor cell communication, we obtained deeper mechanistic insight into these cell-cell interactions. RESULTS: Infiltrating CD68+ macrophages interact with AT/RT tumor cells generating intermediary hybrid-like cells with autonomous communication properties, increasing the cell heterogeneity of AT/RT. By depletion of myeloid cells in AT/RT mouse models followed by scRNA-seq of tumor and non-tumor samples, we demonstrated that tumor formation is hindered. Furthermore, we give mechanistic insights into how myeloid cells contribute to tumorigenesis. IN CONCLUSION: the dynamic and extensive interactions between tumor cells and myeloid cells do not only potentiate cellular heterogeneity but might also induce cellular plasticity associated with the acquisition of resistance to chemotherapy and seem to be essential for AT/RT development.
RARE-02. Craniopharyngiomas diagnosed as incidentalomas - results of KRANIOPHARYNGEOM 2007
Authors: Boekhoff Svenja , Bison Brigitte , Eveslage Maria , Sowithayasakul Panjarat , Müller Hermann L
Published: June 2022

PURPOSE: Childhood-onset craniopharyngiomas (CP) are diagnosed due to clinical symptoms (symCP) or incidentally (incCP). We investigated clinical manifestations and outcome in incCPs and symCPs. METHODS: IncCP were discovered in 4 (3m / 1f) and symCP in 214 (101m / 113f) CP recruited 2007–2014 in KRANIOPHARYNGEOM 2007. Age, sex, height, body mass index (BMI), tumor volume, degree of resection, pre- and postsurgical hypothalamic involvement/lesions, pituitary function and outcome were compared between both subgroups. RESULTS: Reasons for imaging in incCP were cerebral palsy, head trauma, nasal obstruction, and tethered-cord syndrome, whereas headache (44%), visual impairment (25%), and growth retardation (17%) lead to imaging in symCP. Tumor volume at diagnosis was smaller in incCP (median 2.39 cm3; range: 0.14 – 4.10 cm3) when compared with symCP (15.86 cm3; 0.002 – 286.34 cm3). Age, gender, BMI, height, hydrocephalus, tumor location, and hypothalamic involvement at diagnosis of incCP were within the range of these parameters in symCP. Complete resections were achieved more frequently (3/4 patients) in incCP when compared with symCP (20%). Surgical hypothalamic lesions were distributed similar in incCP and symCP. Irradiation was performed only in symCP (33%). No noticeable differences were observed concerning survival rates, endocrine deficiencies, BMI, height, functional capacity and quality of life of the 4 incCP cases when compared with the symCP cohort. CONCLUSIONS: IncCP are rare (1.8%) and characterized by lack of endocrine deficiencies, resulting in normal height and BMI, no hydrocephalus, and smaller tumor volume at diagnosis when compared with symCPs. Outcome of the observed incCP is similar with symCP.