The Dinosauria: Baraminological and Multivariate Patterns

The Dinosauria pose both interesting and challenging questions for creationist systematists. One question is whether new dinosaur discoveries are closing morphospatial gaps between dinosaurian groups, revealing continuous morphological fossil series, such as between coelurosaurians and avialans. Questions such as these underscore the importance of systematics for resolving correct group memberships, including tools for visualizing morphospatial relationships. Baraminic distance correlation (BDC), three-dimensional multidimensional scaling (MDS), and a new method to baraminic studies – principal component analysis (PCA) – were applied to 18 character matrices from 2004. The data included saurischian and ornithischian dinosaur groups including (1) “basal” Saurischia, (2) Ceratosauria (including Coelophysidae), (3) “basal” Tetanurae, (4) Tyrannosauroidea, (5) “Prosauropoda”, (6) Sauropoda, (7) Maniraptoriformes, (8) Therizinosauroidea, and (9) Oviraptorosauria. The ornithischians included (10) “basal” Thyreophora, (11) Stegosauria, (12) Ankylosauria, (13) “basal” Ornithopoda, (14) “basal” Iguanodontia, (15) Hadrosauridae, (16) Pachycephalosauria, (17) “basal” Ceratopsia, and (18) Ceratopsidae. BDC and MDS revealed several potential holobaramins and apobaramins, and PCA identified some divisions not recognized by the traditional methods, but since the datasets are 14 years old, many important taxa are missing. As a result, we performed PCA on 19 newer datasets (from 2009 to 2018) and compared the results, which revealed a substantially clearer picture since only 2004. Dinosaur group ordinations commonly occur within morphospatial clusters or linear series. Holobaramins were revealed mainly as closely-spaced morphospatial series of taxa. Some series were additionally stratomorphic. Assuming holobaramins are discontinuity-bounded morphospatial series of taxa, we estimate 27 potential holobaramins within the newer data. PCA revealed that bird-dinosaur morphospatial relationships vary by dataset. Paravians likely contain two branching morphoseries, connected at the base by dromaeosaurs and avialans. The two morphoseries are functional/ecological, rather than evolutionary. Multivariate analysis offers the potential to improve our understanding of baramins and discontinuity, and provide a new perspective on questions in creation systematics such as bird-dinosaur relationships

An interlaboratory investigation of intrinsic dissolution rate determination using surface dissolution

The pur­pose of this study was to con­duct an in­ter­lab­o­ra­tory ring-study, with six part­ners (aca­d­e­mic and in­dus­trial), in­ves­ti­gat­ing the mea­sure­ment of in­trin­sic dis­so­lu­tion rate (IDR) us­ing sur­face dis­so­lu­tion imag­ing (SDI) equip­ment. Mea­sure­ment of IDR is im­por­tant in phar­ma­ceu­ti­cal re­search as it pro­vides char­ac­ter­is­ing in­for­ma­tion on drugs and their for­mu­la­tions. This work al­lowed us to as­sess the SDI’s in­ter­lab­o­ra­tory per­for­mance for mea­sur­ing IDR us­ing a de­fined stan­dard op­er­at­ing pro­ce­dure (see sup­port­ing in­for­ma­tion) and six drugs as­signed as low (tadalafil, bromocrip­tine me­sy­late), medium (carvedilol, in­domethacin) and high (ibupro­fen, val­sar­tan) sol­u­bil­ity com­pounds. Fasted State Sim­u­lated In­testi­nal Fluid (FaS­SIF) and blank FaS­SIF (with­out sodium tau­ro­cholate and lecithin) (pH 6.5) were used as me­dia. Us­ing the stan­dard­ised pro­to­col an IDR value was ob­tained for all com­pounds and the re­sults show that the over­all IDR rank or­der matched the sol­u­bil­ity rank or­der. In­ter­lab­o­ra­tory vari­abil­ity was also ex­am­ined and it was ob­served that the vari­abil­ity for lower sol­u­bil­ity com­pounds was higher, co­ef­fi­cient of vari­a­tion >50%, than for in­ter­me­di­ate and high sol­u­bil­ity com­pounds, with the ex­cep­tion of in­domethacin in FaS­SIF medium. In­ter lab­o­ra­tory vari­abil­ity is a use­ful de­scrip­tor for un­der­stand­ing the ro­bust­ness of the pro­to­col and the sys­tem vari­abil­ity. On com­par­i­son to an­other pub­lished small-scale IDR study the rank or­der­ing with re­spect to dis­so­lu­tion rate is iden­ti­cal ex­cept for the high sol­u­bil­ity com­pounds. This re­sults in­di­cates that the SDI ro­bustly mea­sures IDR how­ever, no rec­om­men­da­tion on the use of one small scale method over the other is made

Exome array analysis of adverse reactions to fluoropyrimidine-based therapy for gastrointestinal cancer.

Fluoropyrimidines, including 5-fluororacil (5FU) and its pro-drug Capecitabine, are the common treatment for colorectal, breast, neck and head cancers-either as monotherapy or in combination therapy. Adverse reactions (ADRs) to the treatment are common and often result in treatment discontinuation or dose reduction. Factors contributing to ADRs, including genetic variation, are poorly characterized. We performed exome array analysis to identify genetic variants that contribute to adverse reactions. Our final dataset consisted of 504 European ancestry individuals undergoing fluoropyrimidine-based therapy for gastrointestinal cancer. A subset of 254 of these were treated with Capecitabine. All individuals were genotyped on the Illumina HumanExome Array. Firstly, we performed SNP and gene-level analyses of protein-altering variants on the array to identify novel associations the following ADRs, which were grouped into four phenotypes based on symptoms of diarrhea, mucositis, and neutropenia and hand-and-foot syndrome. Secondly, we performed detailed analyses of the HLA region on the same phenotypes after imputing the HLA alleles and amino acids. No protein-altering variants, or sets of protein-altering variants collapsed into genes, were associated with the main outcomes after Bonferroni correction. We found evidence that the HLA region was enriched for associations with Hand-and-Foot syndrome (p = 0.023), but no specific SNPs or HLA alleles were significant after Bonferroni correction. Larger studies will be required to characterize the genetic contribution to ADRs to 5FU. Future studies that focus on the HLA region are likely to be fruitful

Independent and population-specific association of risk variants at the IRGM locus with Crohn's disease

DNA polymorphisms in a region on chromosome 5q33.1 which contains two genes, immunity related GTPase related family, M (IRGM) and zinc finger protein 300 (ZNF300), are associated with Crohn's disease (CD). The deleted allele of a 20 kb copy number variation (CNV) upstream of IRGM was recently shown to be in strong linkage disequilibrium (LD) with the CD-associated single nucleotide polymorphisms and is itself associated with CD (P < 0.01). The deletion was correlated with increased or reduced expression of IRGM in transformed cells in a cell line-dependent manner, and has been proposed as a likely causal variant. We report here that small insertion/deletion polymorphisms in the promoter and 5′ untranslated region of IRGM are, together with the CNV, strongly associated with CD (P = 1.37 × 10−5 to 1.40 × 10−9), and that the CNV and the 5′-untranslated region variant −308(GTTT)5 contribute independently to CD susceptibility (P = 2.6 × 10−7 and P = 2 × 10−5, respectively). We also show that the CD risk haplotype is associated with a significant decrease in IRGM expression (P < 10−12) in untransformed lymphocytes from CD patients. Further analysis of these variants in a Japanese CD case-control sample and of IRGM expression in HapMap populations revealed that neither the IRGM insertion/deletion polymorphisms nor the CNV was associated with CD or with altered IRGM expression in the Asian population. This suggests that the involvement of the IRGM risk haplotype in the pathogenesis of CD requires gene-gene or gene-environment interactions which are absent in Asian populations, or that none of the variants analysed are causal, and that the true causal variants arose after the European-Asian spli

Exome sequencing and genotyping identify a rare variant in NLRP7 gene associated with ulcerative colitis.

Background and Aims Although genome-wide association studies [GWAS] in inflammatory bowel disease [IBD] have identified a large number of common disease susceptibility alleles for both Crohn’s disease [CD] and ulcerative colitis [UC], a substantial fraction of IBD heritability remains unexplained, suggesting that rare coding genetic variants may also have a role in pathogenesis. We used high-throughput sequencing in families with multiple cases of IBD, followed by genotyping of cases and controls, to investigate whether rare protein-altering genetic variants are associated with susceptibility to IBD. Methods Whole-exome sequencing was carried out in 10 families in whom three or more individuals were affected with IBD. A stepwise filtering approach was applied to exome variants, to identify potential causal variants. Follow-up genotyping was performed in 6025 IBD cases [2948 CD; 3077 UC] and 7238 controls. Results Our exome variant analysis revealed coding variants in the NLRP7 gene that were present in affected individuals in two distinct families. Genotyping of the two variants, p.S361L and p.R801H, in IBD cases and controls showed that the p.S361L variant was significantly associated with an increased risk of ulcerative colitis [odds ratio 4.79, p = 0.0039] and IBD [odds ratio 3.17, p = 0.037]. A combined analysis of both variants showed suggestive association with an increased risk of IBD [odds ratio 2.77, p = 0.018]. Conclusions The results suggest that NLRP7 signalling and inflammasome formation may be a significant component in the pathogenesis of IBD

FracPaQ: A MATLAB™ toolbox for the quantification of fracture patterns

The patterns of fractures in deformed rocks are rarely uniform or random. Fracture orientations, sizes, and spatial distributions often exhibit some kind of order. In detail, relationships may exist among the different fracture attributes, e.g. small fractures dominated by one orientation, larger fractures by another. These relationships are important because the mechanical (e.g. strength, anisotropy) and transport (e.g. fluids, heat) properties of rock depend on these fracture attributes and patterns. This paper describes FracPaQ, a new open source, cross-platform toolbox to quantify fracture patterns, including distributions in fracture attributes and their spatial variation. Software has been developed to quantify fracture patterns from 2-D digital images, such as thin section micrographs, geological maps, outcrop or aerial photographs or satellite images. The toolbox comprises a suite of MATLAB™ scripts based on previously published quantitative methods for the analysis of fracture attributes: orientations, lengths, intensity, density and connectivity.An estimate of permeability in 2-D is made using a parallel plate model. The software provides an objective and consistent methodology for quantifying fracture patterns and their variations in 2-D across a wide range of length scales, rock types and tectonic settings. The implemented methods presented are inherently scale independent, and a key task where applicable is analysing and integrating quantitative fracture pattern data from micro-to macro-scales. The toolbox was developed in MATLAB™ and the source code is publicly available on GitHub™ and the Mathworks™ FileExchange. The code runs on any computer with MATLAB installed, including PCs with Microsoft Windows, Apple Macs with Mac OS X, and machines running different flavours of Linux. The application, source code and sample input files are available in open repositories in the hope that other developers and researchers will optimise and extend the functionality for the benefit of the wider community