Please Mind the Gap: Highly Condensed P–N Networks in LiP4N7 and Li3−xP6N11−x(NH)x

Alkali nitridophosphates AP4N7 and A3P6N11 (A=Na, K, Rb, Cs) have been known for decades. However, their Li homologues have remained elusive. In this work, the highly condensed lithium (imido)nitridophosphates LiP4N7 and Li3−xP6N11−x(NH)x (x=1.66(3)) were synthesized from LiPN2 and P3N5 in the multianvil press at 10 GPa. They constitute the first lithium nitridophosphates with 3D networks exhibiting a degree of condensation larger than 0.5 and high thermal stability. LiP4N7 crystallizes in the orthorhombic space group P212121 with a=4.5846(6) Å, b=8.0094(11) Å, and c=13.252(2) Å (Z=4). Li3−xP6N11−x(NH)x crystallizes in the triclinic space group Purn:x-wiley:09476539:media:chem202303251:chem202303251-math-0001 with Z=2, a=4.6911(11) Å, b=7.024(2) Å, c=12.736(3) Å, α=87.726(11), β=80.279(11), and γ=70.551(12)°. Both compounds are stable against hydrolysis in air

Boundary Graph Neural Networks for 3D Simulations

The abundance of data has given machine learning considerable momentum in natural sciences and engineering. However, the modeling of simulated physical processes remains difficult. A key problem is the correct handling of geometric boundaries. While triangularized geometric boundaries are very common in engineering applications, they are notoriously difficult to model by machine learning approaches due to their heterogeneity with respect to size and orientation. In this work, we introduce Boundary Graph Neural Networks (BGNNs), which dynamically modify graph structures to address boundary conditions. Boundary graph structures are constructed via modifying edges, augmenting node features, and dynamically inserting virtual nodes. The new BGNNs are tested on complex 3D granular flow processes of hoppers and rotating drums which are standard components of industrial machinery. Using precise simulations that are obtained by an expensive and complex discrete element method, BGNNs are evaluated in terms of computational efficiency as well as prediction accuracy of particle flows and mixing entropies. Even if complex boundaries are present, BGNNs are able to accurately reproduce 3D granular flows within simulation uncertainties over hundreds of thousands of simulation timesteps, and most notably particles completely stay within the geometric objects without using handcrafted conditions or restrictions

Clinical Follow-Up in Orofacial Clefts—Why Multidisciplinary Care Is the Key

(1) Background: Although most clinicians involved in the treatment of cleft patients agree upon the major importance of interdisciplinary cooperation and many protocols and concepts have been discussed in the literature, there is little evidence of the relevance of continuous interdisciplinary care. We aimed to objectify the type and number of therapeutic decisions resulting from an annual multidisciplinary follow-up. (2) Methods: We retrospectively analyzed the data of all 1126 patients followed up in the weekly consultation hours for cleft patients at university clinics in Leipzig for the years 2005–2020. We assessed the clinical data of every patient and specifically evaluated the treatment decisions taken at different points in time by the participating experts of different specialties. (3) Results: In total, 3470 consultations were included in the evaluation, and in 70% of those, a therapeutic recommendation was given. Each specialty showed certain time frames with intense treatment demand, which partially overlapped. Nearly all therapy recommendations were statistically attached to a certain age (p < 0.001). (4) Conclusions: There is an exceptionally high need for the interdisciplinary assessment of patients with cleft formation. Some developmental phases are of particular importance with regard to regular follow-up and initiation of different treatment protocols. The therapy and checkup of cleft patients should be concentrated in specialized centers

CONAN: copy number variation analysis software for genome-wide association studies

<p>Abstract</p> <p>Background</p> <p>Genome-wide association studies (GWAS) based on single nucleotide polymorphisms (SNPs) revolutionized our perception of the genetic regulation of complex traits and diseases. Copy number variations (CNVs) promise to shed additional light on the genetic basis of monogenic as well as complex diseases and phenotypes. Indeed, the number of detected associations between CNVs and certain phenotypes are constantly increasing. However, while several software packages support the determination of CNVs from SNP chip data, the downstream statistical inference of CNV-phenotype associations is still subject to complicated and inefficient in-house solutions, thus strongly limiting the performance of GWAS based on CNVs.</p> <p>Results</p> <p>CONAN is a freely available client-server software solution which provides an intuitive graphical user interface for categorizing, analyzing and associating CNVs with phenotypes. Moreover, CONAN assists the evaluation process by visualizing detected associations via Manhattan plots in order to enable a rapid identification of genome-wide significant CNV regions. Various file formats including the information on CNVs in population samples are supported as input data.</p> <p>Conclusions</p> <p>CONAN facilitates the performance of GWAS based on CNVs and the visual analysis of calculated results. CONAN provides a rapid, valid and straightforward software solution to identify genetic variation underlying the 'missing' heritability for complex traits that remains unexplained by recent GWAS. The freely available software can be downloaded at <url>http://genepi-conan.i-med.ac.at</url>.</p

Large-scale mitochondrial DNA analysis in Southeast Asia reveals evolutionary effects of cultural isolation in the multi-ethnic population of Myanmar

Background: Myanmar is the largest country in mainland Southeast Asia with a population of 55 million people subdivided into more than 100 ethnic groups. Ruled by changing kingdoms and dynasties and lying on the trade route between India and China, Myanmar was influenced by numerous cultures. Since its independence from British occupation, tensions between the ruling Bamar and ethnic minorities increased. Results: Our aim was to search for genetic footprints of Myanmar’s geographic, historic and sociocultural characteristics and to contribute to the picture of human colonization by describing and dating of new mitochondrial DNA (mtDNA) haplogroups. Therefore, we sequenced the mtDNA control region of 327 unrelated donors and the complete mitochondrial genome of 44 selected individuals according to highest quality standards. Conclusion: Phylogenetic analyses of the entire mtDNA genomes uncovered eight new haplogroups and three unclassified basal M-lineages. The multi-ethnic population and the complex history of Myanmar were reflected in its mtDNA heterogeneity. Population genetic analyses of Burmese control region sequences combined with population data from neighboring countries revealed that the Myanmar haplogroup distribution showed a typical Southeast Asian pattern, but also Northeast Asian and Indian influences. The population structure of the extraordinarily diverse Bamar differed from that of the Karen people who displayed signs of genetic isolation. Migration analyses indicated a considerable genetic exchange with an overall positive migration balance from Myanmar to neighboring countries. Age estimates of the newly described haplogroups point to the existence of evolutionary windows where climatic and cultural changes gave rise to mitochondrial haplogroup diversification in Asia

Mobile Air Quality Studies (MAQS) - an international project

Due to an increasing awareness of the potential hazardousness of air pollutants, new laws, rules and guidelines have recently been implemented globally. In this respect, numerous studies have addressed traffic-related exposure to particulate matter using stationary technology so far. By contrast, only few studies used the advanced technology of mobile exposure analysis. The Mobile Air Quality Study (MAQS) addresses the issue of air pollutant exposure by combining advanced high-granularity spatial-temporal analysis with vehicle-mounted, person-mounted and roadside sensors. The MAQS-platform will be used by international collaborators in order 1) to assess air pollutant exposure in relation to road structure, 2) to assess air pollutant exposure in relation to traffic density, 3) to assess air pollutant exposure in relation to weather conditions, 4) to compare exposure within vehicles between front and back seat (children) positions, and 5) to evaluate "traffic zone"- exposure in relation to non-"traffic zone"-exposure. Primarily, the MAQS-platform will focus on particulate matter. With the establishment of advanced mobile analysis tools, it is planed to extend the analysis to other pollutants including including NO2, SO2, nanoparticles, and ozone

Circadian Transcription Contributes to Core Period Determination in Drosophila

The Clock–Cycle (CLK–CYC) heterodimer constitutes a key circadian transcription complex in Drosophila. CYC has a DNA-binding domain but lacks an activation domain. Previous experiments also indicate that most of the transcriptional activity of CLK–CYC derives from the glutamine-rich region of its partner CLK. To address the role of transcription in core circadian timekeeping, we have analyzed the effects of a CYC–viral protein 16 (VP16) fusion protein in the Drosophila system. The addition of this potent and well-studied viral transcriptional activator (VP16) to CYC imparts to the CLK–CYC-VP16 complex strongly enhanced transcriptional activity relative to that of CLK–CYC. This increase is manifested in flies expressing CYC-VP16 as well as in S2 cells. These flies also have increased levels of CLK–CYC direct target gene mRNAs as well as a short period, implicating circadian transcription in period determination. A more detailed examination of reporter gene expression in CYC-VP16–expressing flies suggests that the short period is due at least in part to a more rapid transcriptional phase. Importantly, the behavioral effects require a period (per) promoter and are therefore unlikely to be merely a consequence of generally higher PER levels. This indicates that the CLK–CYC-VP16 behavioral effects are a consequence of increased per transcription. All of this also suggests that the timing of transcriptional activation and not the activation itself is the key event responsible for the behavioral effects observed in CYC-VP16-expressing flies. The results taken together indicate that circadian transcription contributes to core circadian function in Drosophila

Using Interpretable Machine Learning to Identify Baseline Predictive Factors of Remission and Drug Durability in Crohn’s Disease Patients on Ustekinumab

Ustekinumab has shown efficacy in Crohn's Disease (CD) patients. To identify patient profiles of those who benefit the most from this treatment would help to position this drug in the therapeutic paradigm of CD and generate hypotheses for future trials. The objective of this analysis was to determine whether baseline patient characteristics are predictive of remission and the drug durability of ustekinumab, and whether its positioning with respect to prior use of biologics has a significant effect after correcting for disease severity and phenotype at baseline using interpretable machine learning. Patients' data from SUSTAIN, a retrospective multicenter single-arm cohort study, were used. Disease phenotype, baseline laboratory data, and prior treatment characteristics were documented. Clinical remission was defined as the Harvey Bradshaw Index <= 4 and was tracked longitudinally. Drug durability was defined as the time until a patient discontinued treatment. A total of 439 participants from 60 centers were included and a total of 20 baseline covariates considered. Less exposure to previous biologics had a positive effect on remission, even after controlling for baseline disease severity using a non-linear, additive, multivariable model. Additionally, age, body mass index, and fecal calprotectin at baseline were found to be statistically significant as independent negative risk factors for both remission and drug survival, with further risk factors identified for remission

Genome-Wide Analysis of Light- and Temperature-Entrained Circadian Transcripts in Caenorhabditis elegans

Transcriptional profiling experiments identify light- and temperature-entrained circadian transcripts in C. elegans