Machine Learning-Enhanced Aircraft Landing Scheduling under Uncertainties

This paper addresses aircraft delays, emphasizing their impact on safety and financial losses. To mitigate these issues, an innovative machine learning (ML)-enhanced landing scheduling methodology is proposed, aiming to improve automation and safety. Analyzing flight arrival delay scenarios reveals strong multimodal distributions and clusters in arrival flight time durations. A multi-stage conditional ML predictor enhances separation time prediction based on flight events. ML predictions are then integrated as safety constraints in a time-constrained traveling salesman problem formulation, solved using mixed-integer linear programming (MILP). Historical flight recordings and model predictions address uncertainties between successive flights, ensuring reliability. The proposed method is validated using real-world data from the Atlanta Air Route Traffic Control Center (ARTCC ZTL). Case studies demonstrate an average 17.2% reduction in total landing time compared to the First-Come-First-Served (FCFS) rule. Unlike FCFS, the proposed methodology considers uncertainties, instilling confidence in scheduling. The study concludes with remarks and outlines future research directions

Interaction of CK1δ with γTuSC ensures proper microtubule assembly and spindle positioning.

Casein kinase 1δ (CK1δ) family members associate with microtubule-organizing centers (MTOCs) from yeast to humans, but their mitotic roles and targets have yet to be identified. We show here that budding yeast CK1δ, Hrr25, is a γ-tubulin small complex (γTuSC) binding factor. Moreover, Hrr25's association with γTuSC depends on its kinase activity and its noncatalytic central domain. Loss of Hrr25 kinase activity resulted in assembly of unusually long cytoplasmic microtubules and defects in spindle positioning, consistent with roles in regulation of γTuSC-mediated microtubule nucleation and the Kar9 spindle-positioning pathway, respectively. Hrr25 directly phosphorylated γTuSC proteins in vivo and in vitro, and this phosphorylation promoted γTuSC integrity and activity. Because CK1δ and γTuSC are highly conserved and present at MTOCs in diverse eukaryotes, similar regulatory mechanisms are expected to apply generally in eukaryotes

Some remarks on the argument appealing to nature against synthetic biology

This paper will focus on analyzing the argument with appealing to nature against synthetic biology and provide a counter-argument against it through demonstrating the ambiguity of the concept of nature, denying the existence of a morally significant line between natural and non/unnatural, and disproving the allegations against synthetic biology raised by the argument appealing to nature. The paper consists of two parts following a brief introduction. The first part will describe the argument appealing to nature against synthetic biology, and identify the deficiencies of the argument per se, e.g., the ambiguity of the concept ‘nature’; and the problems in the morally significant line between the natural and the non/unnatural. The second part will discuss the allegations to synthetic biology stemming from this argument, e.g., committing metaphysical and ethical mistakes, and doing possible harms to the environment

Casein Kinase 1 Promotes Initiation of Clathrin-Mediated Endocytosis

SummaryIn budding yeast, over 60 proteins functioning in at least five modules are recruited to endocytic sites with predictable order and timing. However, how sites of clathrin-mediated endocytosis are initiated and stabilized is not well understood. Here, the casein kinase 1 (CK1) Hrr25 is shown to be an endocytic protein and to be among the earliest proteins to appear at endocytic sites. Hrr25 absence or overexpression decreases or increases the rate of endocytic site initiation, respectively. Ede1, an early endocytic Eps15-like protein important for endocytic initiation, is an Hrr25 target and is required for Hrr25 recruitment to endocytic sites. Hrr25 phosphorylation of Ede1 is required for Hrr25-Ede1 interaction and promotes efficient initiation of endocytic sites. These observations indicate that Hrr25 kinase and Ede1 cooperate to initiate and stabilize endocytic sites. Analysis of the mammalian homologs CK1δ/ε suggests a conserved role for these protein kinases in endocytic site initiation and stabilization

NTCP Deficiency Affects the Levels of Circulating Bile Acids and Induces Osteoporosis

BackgroundThe p.Ser267Phe mutation in the SLC10A1 gene can cause NTCP deficiency. However, the full clinical presentation of p.Ser267Phe homozygous individuals and its long-term consequences remain unclear. Hence, in the present study, we characterized the phenotypic characteristics of NTCP deficiency and evaluated its long-term prognosis.MethodsTen NTCP p.Ser267Phe homozygous individuals were recruited and a comprehensive medical evaluation with a 5-year follow-up observation was performed. The phenotypic characteristics of NTCP deficiency were also demonstrated using an NTCP-global knockout mouse model.ResultsDuring the 5-year follow-up observation of 10 NTCP p.Ser267Phe homozygous adults, we found that the most common phenotypic features of NTCP deficiency in adults were hypercholanemia, vitamin D deficiency, bone loss, and gallbladder abnormalities. The profile of bile acids (BAs) in the serum was significantly altered in these individuals and marked by both elevated proportion and concentration of primary and conjugated BAs. Moreover, the NTCP deficiency led to increased levels of serum BAs, decreased levels of vitamin D, and aggravated the osteoporotic phenotype induced by estrogen withdrawal in mice.ConclusionsBoth mice and humans with NTCP deficiency presented hypercholanemia and were more prone to vitamin D deficiency and aggravated osteoporotic phenotype. Therefore, we recommend monitoring the levels of BAs and vitamin D, bone density, and abdominal ultrasounds in individuals with NTCP deficiency

Load-Balanced Parallel Implementation on GPUs for Multi-Scalar Multiplication Algorithm

Multi-scalar multiplication (MSM) is an important building block in most of elliptic-curve-based zero-knowledge proof systems, such as Groth16 and PLONK. Recently, Lu et al. proposed cuZK, a new parallel MSM algorithm on GPUs. In this paper, we revisit this scheme and present a new GPU-based implementation to further improve the performance of MSM algorithm. First, we propose a novel method for mapping scalars into Pippenger’s bucket indices, largely reducing the number of buckets compared to the original Pippenger algorithm. Second, in the case that memory is sufficient, we develop a new efficient algorithm based on homogeneous coordinates in the bucket accumulation phase. Moreover, our accumulation phase is load-balanced, which means the parallel speedup ratio is almost linear growth as the number of device threads increases. Finally, we also propose a parallel layered reduction algorithm for the bucket aggregation phase, whose time complexity remains at the logarithmic level of the number of buckets. The implementation results over the BLS12-381 curve on the V100 graphics card show that our proposed algorithm achieves up to 1.998x, 1.821x and 1.818x speedup compared to cuZK at scales of 221, 222, and 223, respectively

Determination of 4 Kinds of β-Agonists Residues in Braised Meat by Ultra Performance Liquid Chromatography-Tandem Mass Spectrometry

An ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS) method was developed for the determination of four β-agonists (terbutaline, clenbuterol, ractopamine, salbutamol) in braised meat. Samples were hydrolyzed by β-glucuronidase and cleaned up by an SLS solid phase extraction column. The separation was performed on a Thermo Hypersil Gold C18 column with a gradient elution of 0.1% formic acid water and acetonitrile as mobile phases, ESI+ was used for multiple response monitoring (MRM) and quantitative analysis by internal standard method. The linear relationship of the four β-agonists was good in the concentration range of 0.5 μg/L to 9.5 μg/L, and the correlation coefficient (r) was greater than 0.9988. The limit of detection (LOD) was 0.1 μg/kg, and the limit of quantitation (LOQ) was 0.3 μg/kg. The recoveries were 87.9%~113.7% and RSDs were 1.48%~9.32% at three spiked levels (1, 5 and 9 μg/kg). In a total of 162 batches of braised meat samples, one sample of braised pig’s trotter was found to contain 1.51 μg/kg of clenbuterol and 3.65 μg/kg of ractopamine. Additionally, another sample of braised lamb was found to contain 11.5 μg/kg of clenbuterol. The method is rapid and accurate, and can be used for qualitative and quantitative determination of four β-agonists (terbutaline, clenbuterol, ractopamine, salbutamol) in braised meat

Multi-omics analyses unravel DNA damage repair-related clusters in breast cancer with experimental validation

BackgroundAs one of the most common malignancies worldwide, breast cancer (BC) exhibits high heterogeneity of molecular phenotypes. The evolving view regarding DNA damage repair (DDR) is that it is context-specific and heterogeneous, but its role in BC remains unclear.MethodsMulti-dimensional data of transcriptomics, genomics, and single-cell transcriptome profiling were obtained to characterize the DDR-related features of BC. We collected 276 DDR-related genes based on the Molecular Signature Database (MSigDB) database and previous studies. We acquired public datasets included the SCAN-B dataset (GEO: GSE96058), METABRIC database, and TCGA-BRCA database. Corresponding repositories such as transcriptomics, genomics, and clinical information were also downloaded. We selected scRNA-seq data from GEO: GSE176078, GSE114727, GSE161529, and GSE158724. Bulk RNA-seq data from GEO: GSE176078, GSE18728, GSE5462, GSE20181, and GSE130788 were extracted for independent analyses.ResultsThe DDR classification was constructed in the SCAN-B dataset (GEO: GSE96058) and METABRIC database, Among BC patients, there were two clusters with distinct clinical and molecular characteristics: the DDR-suppressed cluster and the DDR-active cluster. A superior survival rate is found for tumors in the DDR-suppressed cluster, while those with the DDR-activated cluster tend to have inferior prognoses and clinically aggressive behavior. The DDR classification was validated in the TCGA-BRCA cohort and shown similar results. We also found that two clusters have different pathway activities at the genomic level. Based on the intersection of the different expressed genes among these cohorts, we found that PRAME might play a vital role in DDR. The DDR classification was then enabled by establishing a DDR score, which was verified through multilayer cohort analysis. Furthermore, our results revealed that malignant cells contributed more to the DDR score at the single-cell level than nonmalignant cells. Particularly, immune cells with immunosuppressive properties (such as FOXP3+ CD4+ T cells) displayed higher DDR scores among those with distinguishable characteristics.ConclusionCollectively, this study performs general analyses of DDR heterogeneity in BC and provides insight into the understanding of individualized molecular and clinicopathological mechanisms underlying unique DDR profiles

Vac8p, an Armadillo Repeat Protein, Coordinates Vacuole Inheritance With Multiple Vacuolar Processes

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/74978/1/j.1600-0854.2006.00458.x.pd