Patterns on the numerical duplication by their admissibility degree

We develop the theory of patterns on numerical semigroups in terms of the admissibility degree. We prove that the Arf pattern induces every strongly admissible pattern, and determine all patterns equivalent to the Arf pattern. We study patterns on the numerical duplication $S \Join^d E$ when $d \gg0$. We also provide a definition of patterns on rings

Primary familial brain calcification linked to deletion of 5' noncoding region of SLC20A2

OBJECTIVES: Primary familial brain calcification (PFBC) is a rare neurological disease often inherited as a dominant trait. Mutations in four genes (SLC20A2, PDGFB, PDGFRB, and XPR1) have been reported in patients with PFBC. Of these, point mutations or small deletions in SLC20A2 are most common. Thus far, only one large deletion covering entire SLC20A2 and several smaller, exonic deletions of SLC20A2 have been reported. The aim of this study was to identify the causative gene defect in a Finnish PFBC family with three affected patients. MATERIALS AND METHODS: A Finnish family with three PFBC patients and five unaffected subjects was studied. Sanger sequencing was used to exclude mutations in the coding and splice site regions of SLC20A2, PDGFRB, and PDGFB. Whole-exome (WES) and whole-genome sequencing (WGS) were performed to identify the causative mutation. A SNP array was used in segregation analysis. RESULTS: Copy number analysis of the WGS data revealed a heterozygous deletion of ~578 kb on chromosome 8. The deletion removes the 5' UTR region, the noncoding exon 1 and the putative promoter region of SLC20A2 as well as the coding regions of six other genes. CONCLUSIONS: Our results support haploinsufficiency of SLC20A2 as a pathogenetic mechanism in PFBC. Analysis of copy number variations (CNVs) is emerging as a crucial step in the molecular genetic diagnostics of PFBC, and it should not be limited to coding regions, as causative variants may reside in the noncoding parts of known disease-associated genes

Identification of Novel Candidate Oncogenes in Chromosome Region 17p11.2-p12 in Human Osteosarcoma

Osteosarcoma is the most common primary malignancy of bone. The tumours are characterized by high genomic instability, including the occurrence of multiple regions of amplifications and deletions. Chromosome region 17p11.2–p12 is amplified in about 25% of cases. In previous studies, COPS3 and PMP22 have been identified as candidate oncogenes in this region. Considering the complexity and variation of the amplification profiles for this segment, the involvement of additional causative oncogenes is to be expected. The aim of the present investigation is to identify novel candidate oncogenes in 17p11.2–p12. We selected 26 of in total 85 osteosarcoma samples (31%) with amplification events in 17p11.2–p12, using quantitative PCR for 8 marker genes. These were subjected to high-resolution SNP array analysis and subsequent GISTIC analysis to identify the most significantly amplified regions. Two major amplification peaks were found in the 17p11.2–p12 region. Overexpression as a consequence of gene amplification is a major mechanism for oncogene activation in tumours. Therefore, to identify the causative oncogenes, we next determined expression levels of all genes within the two segments using expression array data that could be generated for 20 of the selected samples. We identified 11 genes that were overexpressed through amplification in at least 50% of cases. Nine of these, c17orf39, RICH2, c17orf45, TOP3A, COPS3, SHMT1, PRPSAP2, PMP22, and RASD1, demonstrated a significant association between copy number and expression level. We conclude that these genes, including COPS3 and PMP22, are candidate oncogenes in 17p11.2–p12 of importance in osteosarcoma tumourigenesis

Rapid export of waters formed by convection near the Irminger Sea's western boundary

The standard view of the overturning circulation emphasizes the role of convection, yet for waters to contribute to overturning, they must not only be transformed to higher densities but also exported equatorward. From novel mooring observations in the Irminger Sea (2014–2016), we describe two water masses that are formed by convection and show that they have different rates of export in the western boundary current. Upper Irminger Sea Intermediate Water appears to form near the boundary current and is exported rapidly within 3 months of its formation. Deep Irminger Sea Intermediate Water forms in the basin interior and is exported on longer time scales. The subduction of these waters into the boundary current is consistent with an eddy transport mechanism. Our results suggest that light intermediate waters can contribute to overturning as much as waters formed by deeper convection and that the export time scales of both project onto overturning variability. Plain Language Summary The deep ocean can regulate the Earth's climate by storing carbon and heat. At high latitudes, waters are cooled by the atmosphere and sink, but they can only be successfully stored in the deep ocean if they are exported toward the equator. In this study, we analyze new mooring observations in the Irminger Sea to investigate the cooling and export of high‐latitude waters. In addition to the well‐documented waters that are cooled in the center of the Irminger Sea, we find that saltier waters are cooled near the western boundary current. Both of these water types make it into boundary current and are exported. Our observations are consistent with the dynamics of swirling eddy motions. The eddy transport process is more effective for the waters cooled near the boundary current, implying that cooling near boundary currents may be more important for the climate than has been appreciated to date

A non-APOE polygenic risk score for Alzheimer's disease is associated with CSF neurofilament light in a representative sample of cognitively unimpaired 70-year-olds

The effect of Alzheimer's disease (AD) polygenic risk scores (PRSs) on amyloid and tau pathophysiology and neurodegeneration in cognitively unimpaired older adults is not known in detail. This study aims to investigate non-APOE AD-PRS and APOE ε4 in relation to AD pathophysiology evaluated by cerebrospinal fluid (CSF) biomarkers in a population-based sample of 70-year-olds. A total of 303 dementia-free individuals from the Gothenburg H70 Birth Cohort Studies were included. Genotyping was performed using the NeuroChip, and AD-PRSs were calculated. CSF levels of amyloid-β (Aβ42), total tau (t-tau), phosphorylated tau (p-tau), neurogranin (Ng), and neurofilament light (NfL) were measured with ELISA. Associations were found between non-APOE PRS and both NfL (p=0.001) and Aβ42 (p=0.02), and between APOE ε4 and Aβ42 (p=1e-10), t-tau (p=5e-4), and p-tau (p=0.002). Similar results were observed when only including individuals with CDR=0, except for no evidence of an association between non-APOE PRS and Aβ42. There was an interaction between non-APOE PRS and Aβ42 pathology status in relation to NfL (p=0.005); association was only present in individuals without Aβ42 pathology (p=0.0003). In relation to Aβ42, there was a borderline interaction (p=0.06) between non-APOE PRS and APOE ε4; association was present in ε4 carriers only (p=0.03). Similar results were observed in individuals with CDR=0 (n=246). In conclusion, among cognitively healthy 70-year-olds from the general population genetic risk of AD beyond the APOE locus was associated with NfL in individuals without Aβ42 pathology, and with Aβ42 in APOE ε4 carriers, suggesting these associations are driven by different mechanisms

Thermopower in the strongly overdoped region of single-layer Bi2Sr2CuO6+d superconductor

The evolution of the thermoelectric power S(T) with doping, p, of single-layer Bi2Sr2CuO6+d ceramics in the strongly overdoped region is studied in detail. Analysis in term of drag and diffusion contributions indicates a departure of the diffusion from the T-linear metallic behavior. This effect is increased in the strongly overdoped range (p~0.2-0.28) and should reflect the proximity of some topological change.Comment: 4 pages, 4 figure