SYSTEMS ANALYSIS APPROACH TO SELECTION OF FARM EQUIPMENT

Farm Management,

Biostratigraphy of Middle and Late Pennsylvanian (Desmoinesian-Virgilian) ammonoids

New stratigraphic ranges for genera of Desmoinesian-Virgilian ammonoids are presented, based on analysis of 40,000 specimens collected from over 70 ammonoid-bearing horizons that represent at least 40 successive stratigraphic levels in the North American midcontinent. These range revisions indicate that current generic-level ammonoid zonations are inadequate, especially for correlation of Pennsylvanian series and stage boundaries. Six high-confidence, largely generic-level first-occurrence zones are proposed for the Desmoinesian through Virgilian stages: Wellerites Zone, Eothalassoceras Zone, Pennoceras Zone, Preshumardites Zone, Pseudaktubites Zone, and Shumardites Zone. Fifteen zones of lesser confidence for correlation are also suggested. The Shumarditidae Plummer & Scott, 1937, is emended to include Preshumardites Plummer & Scott, 1937, Pseudaktubites gen. nov. (type species, Preshumardites stainbrooki Plummer & Scott, 1937), and Shumardites Smith, 1903. Early Permian (Sakmarian) species previously assigned to Preshumardites are reassigned to Andrianovia gen. nov. (type species ?Preshumardites sakmarae Ruzhencev, 1938). Aktubites Ruzhencev, 1955, Eoshumardites Popov, 1960, and Parashumardites Ruzhencev, 1939, previously included in the Shumarditidae, are assigned to the new family Parashumarditidae. Eovidrioceras inexpectans gen. nov., sp. nov. is included and is interpreted as the ancestor of the cyclobacean family Vidrioceratidae Plummer & Scott, 1937. The base of the revised Wellerites Zone, defined by the first occurrence of the nominate genus, approximates but does not coincide with the Atokan-Desmoinesian boundary. Recorrelation of the stratigraphic level of the Collinsville, Oklahoma, ammonoid locality from the "Seminole Formation" (basal Missourian) to the Holdenville Formation (upper Desmoinesian), based on lithostratigraphic evidence, effectively places the first occurrence of Eothalassoceras in the upper Desmoinesian. Because Wellerites apparently became extinct before the end of the Desmoinesian, the revised Eothalassoceras Zone is used to represent the upper Desmoinesian. The Middle-Upper Pennsylvanian boundary (Desmoinesian-Missourian boundary) can be recognized by the appearance of Pennoceras, which defines the base of the new Pennoceras Zone. The Pennoceras Zone is an excellent indicator of lower Missourian strata in the northern midcontinent, north-central Texas, the Marathon Uplift, and the Appalachian Basin. The new Preshumardites Zone occupies most of the upper part of the Missourian Stage. The appearance of the ancestral shumarditid Pseudaktubites, which defines the base of the new Pseudaktubites Zone, occurs one cycle below the Missourian-Virgilian boundary, which is currently recognized at the top of the South Bend Limestone Member in eastern Kansas. No recognizable biostratigraphic event coincides with the South Bend Member, thereby resulting in an uncorrelatable chronostratigraphic boundary. The largest changeover in ammonoid faunas takes place at the base of strata containing the upper part of the Pseudaktubites Zone (Pseudaktubites stainbrooki Subzone). The base of the Pseudaktubites stainbrooki Subzone is stratigraphically near the original Missourian-Virgilian boundary. It is recommended that the stratigraphic level containing the base of the Pseudaktubites stainbrooki Subzone be adopted as the official base of the Virgilian Stage. Recognition of the upper subzone of the Pseudaktubites Zone (Pseudaktubites stainbrooki Subzone) within the Colony Creek Shale Member in north-central Texas places the base of the Virgilian within the upper part of the Canyon Group and substantially below the current position at the Canyon-Cisco group boundary. Shumardites, a taxon previously used to mark the base of the Virgilian Stage, appears in early middle Virgilian strata; consequently, the revised Shumardites Zone represents the middle-upper Virgilian interval

Biostratigraphy of Middle and Late Pennsylvanian (Desmoinesian-Virgilian) ammonoids

New stratigraphic ranges for genera of Desmoinesian-Virgilian ammonoids are presented, based on analysis of 40,000 specimens collected from over 70 ammonoid-bearing horizons that represent at least 40 successive stratigraphic levels in the North American midcontinent. These range revisions indicate that current generic-level ammonoid zonations are inadequate, especially for correlation of Pennsylvanian series and stage boundaries. Six high-confidence, largely generic-level first-occurrence zones are proposed for the Desmoinesian through Virgilian stages: Wellerites Zone, Eothalassoceras Zone, Pennoceras Zone, Preshumardites Zone, Pseudaktubites Zone, and Shumardites Zone. Fifteen zones of lesser confidence for correlation are also suggested. The Shumarditidae Plummer & Scott, 1937, is emended to include Preshumardites Plummer & Scott, 1937, Pseudaktubites gen. nov. (type species, Preshumardites stainbrooki Plummer & Scott, 1937), and Shumardites Smith, 1903. Early Permian (Sakmarian) species previously assigned to Preshumardites are reassigned to Andrianovia gen. nov. (type species ?Preshumardites sakmarae Ruzhencev, 1938). Aktubites Ruzhencev, 1955, Eoshumardites Popov, 1960, and Parashumardites Ruzhencev, 1939, previously included in the Shumarditidae, are assigned to the new family Parashumarditidae. Eovidrioceras inexpectans gen. nov., sp. nov. is included and is interpreted as the ancestor of the cyclobacean family Vidrioceratidae Plummer & Scott, 1937. The base of the revised Wellerites Zone, defined by the first occurrence of the nominate genus, approximates but does not coincide with the Atokan-Desmoinesian boundary. Recorrelation of the stratigraphic level of the Collinsville, Oklahoma, ammonoid locality from the "Seminole Formation" (basal Missourian) to the Holdenville Formation (upper Desmoinesian), based on lithostratigraphic evidence, effectively places the first occurrence of Eothalassoceras in the upper Desmoinesian. Because Wellerites apparently became extinct before the end of the Desmoinesian, the revised Eothalassoceras Zone is used to represent the upper Desmoinesian. The Middle-Upper Pennsylvanian boundary (Desmoinesian-Missourian boundary) can be recognized by the appearance of Pennoceras, which defines the base of the new Pennoceras Zone. The Pennoceras Zone is an excellent indicator of lower Missourian strata in the northern midcontinent, north-central Texas, the Marathon Uplift, and the Appalachian Basin. The new Preshumardites Zone occupies most of the upper part of the Missourian Stage. The appearance of the ancestral shumarditid Pseudaktubites, which defines the base of the new Pseudaktubites Zone, occurs one cycle below the Missourian-Virgilian boundary, which is currently recognized at the top of the South Bend Limestone Member in eastern Kansas. No recognizable biostratigraphic event coincides with the South Bend Member, thereby resulting in an uncorrelatable chronostratigraphic boundary. The largest changeover in ammonoid faunas takes place at the base of strata containing the upper part of the Pseudaktubites Zone (Pseudaktubites stainbrooki Subzone). The base of the Pseudaktubites stainbrooki Subzone is stratigraphically near the original Missourian-Virgilian boundary. It is recommended that the stratigraphic level containing the base of the Pseudaktubites stainbrooki Subzone be adopted as the official base of the Virgilian Stage. Recognition of the upper subzone of the Pseudaktubites Zone (Pseudaktubites stainbrooki Subzone) within the Colony Creek Shale Member in north-central Texas places the base of the Virgilian within the upper part of the Canyon Group and substantially below the current position at the Canyon-Cisco group boundary. Shumardites, a taxon previously used to mark the base of the Virgilian Stage, appears in early middle Virgilian strata; consequently, the revised Shumardites Zone represents the middle-upper Virgilian interval

Phenotype Sequencing: Identifying the Genes That Cause a Phenotype Directly from Pooled Sequencing of Independent Mutants

Random mutagenesis and phenotype screening provide a powerful method for dissecting microbial functions, but their results can be laborious to analyze experimentally. Each mutant strain may contain 50–100 random mutations, necessitating extensive functional experiments to determine which one causes the selected phenotype. To solve this problem, we propose a “Phenotype Sequencing” approach in which genes causing the phenotype can be identified directly from sequencing of multiple independent mutants. We developed a new computational analysis method showing that 1. causal genes can be identified with high probability from even a modest number of mutant genomes; 2. costs can be cut many-fold compared with a conventional genome sequencing approach via an optimized strategy of library-pooling (multiple strains per library) and tag-pooling (multiple tagged libraries per sequencing lane). We have performed extensive validation experiments on a set of E. coli mutants with increased isobutanol biofuel tolerance. We generated a range of sequencing experiments varying from 3 to 32 mutant strains, with pooling on 1 to 3 sequencing lanes. Our statistical analysis of these data (4099 mutations from 32 mutant genomes) successfully identified 3 genes (acrB, marC, acrA) that have been independently validated as causing this experimental phenotype. It must be emphasized that our approach reduces mutant sequencing costs enormously. Whereas a conventional genome sequencing experiment would have cost $7,200 in reagents alone, our Phenotype Sequencing design yielded the same information value for only$1200. In fact, our smallest experiments reliably identified acrB and marC at a cost of only $110–$340

HO_x chemistry during INTEX-A 2004: Observation, model calculation, and comparison with previous studies

OH and HO_2 were measured with the Airborne Tropospheric Hydrogen Oxides Sensor (ATHOS) as part of a large measurement suite from the NASA DC-8 aircraft during the Intercontinental Chemical Transport Experiment-A (INTEX-A). This mission, which was conducted mainly over North America and the western Atlantic Ocean in summer 2004, was an excellent test of atmospheric oxidation chemistry. The HOx results from INTEX-A are compared to those from previous campaigns and to results for other related measurements from INTEX-A. Throughout the troposphere, observed OH was generally 0.95 of modeled OH; below 8 km, observed HO_2 was generally 1.20 of modeled HO_2. This observed-to-modeled comparison is similar to that for TRACE-P, another midlatitude study for which the median observed-to-modeled ratio was 1.08 for OH and 1.34 for HO_2, and to that for PEM-TB, a tropical study for which the median observed-to-modeled ratio was 1.17 for OH and 0.97 for HO_2. HO_2 behavior above 8 km was markedly different. The observed-to-modeled HO_2 ratio increased from ∼1.2 at 8 km to ∼3 at 11 km with the observed-to-modeled ratio correlating with NO. Above 8 km, the observed-to-modeled HO_2 and observed NO were both considerably greater than observations from previous campaigns. In addition, the observed-to-modeled HO_2/OH, which is sensitive to cycling reactions between OH and HO_2, increased from ∼1.5 at 8 km to almost 3.5 at 11 km. These discrepancies suggest a large unknown HO_x source and additional reactants that cycle HO_x from OH to HO_2. In the continental planetary boundary layer, the observed-to-modeled OH ratio increased from 1 when isoprene was less than 0.1 ppbv to over 4 when isoprene was greater than 2 ppbv, suggesting that forests throughout the United States are emitting unknown HO_x sources. Progress in resolving these discrepancies requires a focused research activity devoted to further examination of possible unknown OH sinks and HO_x sources

Dynamics of mitochondrial heteroplasmy in three families investigated via a repeatable re-sequencing study

Background: Originally believed to be a rare phenomenon, heteroplasmy - the presence of more than one mitochondrial DNA (mtDNA) variant within a cell, tissue, or individual - is emerging as an important component of eukaryotic genetic diversity. Heteroplasmies can be used as genetic markers in applications ranging from forensics to cancer diagnostics. Yet the frequency of heteroplasmic alleles may vary from generation to generation due to the bottleneck occurring during oogenesis. Therefore, to understand the alterations in allele frequencies at heteroplasmic sites, it is of critical importance to investigate the dynamics of maternal mtDNA transmission. Results: Here we sequenced, at high coverage, mtDNA from blood and buccal tissues of nine individuals from three families with a total of six maternal transmission events. Using simulations and re-sequencing of clonal DNA, we devised a set of criteria for detecting polymorphic sites in heterogeneous genetic samples that is resistant to the noise originating from massively parallel sequencing technologies. Application of these criteria to nine human mtDNA samples revealed four heteroplasmic sites. Conclusions: Our results suggest that the incidence of heteroplasmy may be lower than estimated in some other recent re-sequencing studies, and that mtDNA allelic frequencies differ significantly both between tissues of the same individual and between a mother and her offspring. We designed our study in such a way that the complete analysis described here can be repeated by anyone either at our site or directly on the Amazon Cloud. Our computational pipeline can be easily modified to accommodate other applications, such as viral re-sequencing

HOx Observation and Model Comparison During INTEX-A 2004

OH and HO2 were measured with the Airborne Tropospheric Hydrogen Oxides Sensor (ATHOS) as part of a large measurement suite from the NASA DC-8 aircraft during the Intercontinental Chemical Transport Experiment - A (INTEX-A). This mission, which was conducted mainly over North America and the western Atlantic Ocean in summer 2004, was an excellent test of atmospheric oxidation chemistry. Throughout the troposphere, observed OH was generally 0.60 of the modeled OH; below 8 km, observed HO2 was generally 0.78 of modeled HO2. If the over-prediction of tropospheric OH is not due to an instrument calibration error, then it implied less global tropospheric oxidation capacity and longer lifetimes for gases like methane and methyl chloroform than currently thought. This discrepancy falls well outside uncertainties in both the OH measurement and rate coefficients for known reactions and points to a large unknown OH loss. If the modeled OH is forced to agree with observed values by introducing of an undefined OH loss that removed HOx (HOx=OH+HO2), the observed and modeled HO2 and HO2/OH ratios are largely reconciled within the measurement uncertainty. HO2 behavior above 8 km was markedly different. The observed-to-modeled ratio correlating with NO. The observed-to-modeled HO2 ratio increased from approximately 1 at 8 km to more than approximately 2.5 at 11 km with the observed-to-modeled ratio correlating with NO. The observed-to-modeled HO2 and NO were both considerably greater than observations from previous campaigns. In addition, the observed-to-modeled HO2/OH, which is sensitive to cycling reactions between OH and HO2, increased from approximately 1.2 at 8 km to almost 4 above 11 km. In contrast to the lower atmosphere, these discrepancies above 8 km suggest a large unknown HOx source and additional reactants that cycle HOx from OH to HO2. In the continental planetary boundary layer, the OH observed-to-modeled ratio increased from 0.6 when isoprene was less than 0.1 ppbv to over 3 when isoprene was greater than 2 ppbv, suggesting that forests throughout the United States are emitting unknown HOx sources. Progress in resolving these discrepancies requires further examinations of possible unknown OH sinks and HOx sources and a focused research activity devoted to ascertaining the accuracy of the OH and HO2 measurements

Genetics of Adverse Reactions to Haloperidol in a Mouse Diallel: A Drug–Placebo Experiment and Bayesian Causal Analysis

Haloperidol is an efficacious antipsychotic drug that has serious, unpredictable motor side effects that limit its utility and cause noncompliance in many patients. Using a drug–placebo diallel of the eight founder strains of the Collaborative Cross and their F1 hybrids, we characterized aggregate effects of genetics, sex, parent of origin, and their combinations on haloperidol response. Treating matched pairs of both sexes with drug or placebo, we measured changes in the following: open field activity, inclined screen rigidity, orofacial movements, prepulse inhibition of the acoustic startle response, plasma and brain drug level measurements, and body weight. To understand the genetic architecture of haloperidol response we introduce new statistical methodology linking heritable variation with causal effect of drug treatment. Our new estimators, “difference of models” and “multiple-impute matched pairs”, are motivated by the Neyman–Rubin potential outcomes framework and extend our existing Bayesian hierarchical model for the diallel (Lenarcic et al. 2012). Drug-induced rigidity after chronic treatment was affected by mainly additive genetics and parent-of-origin effects (accounting for 28% and 14.8% of the variance), with NZO/HILtJ and 129S1/SvlmJ contributions tending to increase this side effect. Locomotor activity after acute treatment, by contrast, was more affected by strain-specific inbreeding (12.8%). In addition to drug response phenotypes, we examined diallel effects on behavior before treatment and found not only effects of additive genetics (10.2–53.2%) but also strong effects of epistasis (10.64–25.2%). In particular: prepulse inhibition showed additivity and epistasis in about equal proportions (26.1% and 23.7%); there was evidence of nonreciprocal epistasis in pretreatment activity and rigidity; and we estimated a range of effects on body weight that replicate those found in our previous work. Our results provide the first quantitative description of the genetic architecture of haloperidol response in mice and indicate that additive, dominance-like inbreeding and parent-of-origin effects contribute strongly to treatment effect heterogeneity for this drug

Genome-wide meta-analysis of cerebral white matter hyperintensities in patients with stroke.

OBJECTIVE: For 3,670 stroke patients from the United Kingdom, United States, Australia, Belgium, and Italy, we performed a genome-wide meta-analysis of white matter hyperintensity volumes (WMHV) on data imputed to the 1000 Genomes reference dataset to provide insights into disease mechanisms. METHODS: We first sought to identify genetic associations with white matter hyperintensities in a stroke population, and then examined whether genetic loci previously linked to WMHV in community populations are also associated in stroke patients. Having established that genetic associations are shared between the 2 populations, we performed a meta-analysis testing which associations with WMHV in stroke-free populations are associated overall when combined with stroke populations. RESULTS: There were no associations at genome-wide significance with WMHV in stroke patients. All previously reported genome-wide significant associations with WMHV in community populations shared direction of effect in stroke patients. In a meta-analysis of the genome-wide significant and suggestive loci (p < 5 × 10(-6)) from community populations (15 single nucleotide polymorphisms in total) and from stroke patients, 6 independent loci were associated with WMHV in both populations. Four of these are novel associations at the genome-wide level (rs72934505 [NBEAL1], p = 2.2 × 10(-8); rs941898 [EVL], p = 4.0 × 10(-8); rs962888 [C1QL1], p = 1.1 × 10(-8); rs9515201 [COL4A2], p = 6.9 × 10(-9)). CONCLUSIONS: Genetic associations with WMHV are shared in otherwise healthy individuals and patients with stroke, indicating common genetic susceptibility in cerebral small vessel disease.Funding for collection, genotyping, and analysis of stroke samples was provided by Wellcome Trust Case Control Consortium-2, a functional genomics grant from the Wellcome Trust (DNA-Lacunar), the Stroke Association (DNA-lacunar), the Intramural Research Program of National Institute of Ageing (Massachusetts General Hospital [MGH] and Ischemic Stroke Genetics Study [ISGS]), National Institute of Neurological Disorders and Stroke (Siblings With Ischemic Stroke Study, ISGS, and MGH), the American Heart Association/Bugher Foundation Centers for Stroke Prevention Research (MGH), Deane Institute for Integrative Study of Atrial Fibrillation and Stroke (MGH), National Health and Medical Research Council (Australian Stroke Genetics Collaborative), and Italian Ministry of Health (Milan). Additional support for sample collection came from the Medical Research Council, National Institute of Health Research Biomedical Research Centre and Acute Vascular Imaging Centre (Oxford), Wellcome Trust and Binks Trust (Edinburgh), and Vascular Dementia Research Foundation (Munich). MT is supported by a project grant from the Stroke Association (TSA 2013/01). HSM is supported by an NIHR Senior Investigator award. HSM and SB are supported by the NIHR Cambridge University Hospitals Comprehensive Biomedical Research Centre. VT and RL are supported by grants from FWO Flanders. PR holds NIHR and Wellcome Trust Senior Investigator Awards. PAS is supported by an MRC Fellowship. CML’s research is supported by the National Institute for Health Research Biomedical Research Centre (BRC) based at Guy's and St Thomas' NHS Foundation Trust and King's College London, and the BRC for Mental Health at South London and Maudsley NHS Foundation Trust and King’s College London. This is the final version of the article. It first appeared from Wolters Kluwer via http://dx.doi.org/10.1212/WNL.000000000000226

Defining and simulating open-ended novelty: requirements, guidelines, and challenges

The open-endedness of a system is often defined as a continual production of novelty. Here we pin down this concept more fully by defining several types of novelty that a system may exhibit, classified as variation, innovation, and emergence. We then provide a meta-model for including levels of structure in a system’s model. From there, we define an architecture suitable for building simulations of open-ended novelty-generating systems and discuss how previously proposed systems fit into this framework. We discuss the design principles applicable to those systems and close with some challenges for the community