An investigation of extensional tectonics of southern California

Geologic mapping and interpretation of Landsat TM imagery has filled in a significant gap in the geologic database for southwestern Arizona and southeastern California. The new data acquired, along with interpretation of existing data, forms the basis for a proposed reconstruction of late Tertiary faults in these regions. This reconstruction integrates available geological and geophysical data to define the eastern limit of deformation related to the San Andreas fault, and has significant implications for other recently proposed reconstructions of Tertiary deformation in the region. This progress in interpreting deformation during the last 10 Ma in the region forms a foundation for developing and testing models of older deformation in this region, including the initiation of San Andreas fault system, and the interaction of Early Miocene extension in the Basin and Range with the evolving San Andreas system

The California Coast Ranges

Western California between the 37th and 40th parallels is part of an active mobile orogenic belt in which sedimentation, deformation, volcanism, and plutonism have been intimately associated since the mid-Mesozoic. At present, the region is still undergoing folding and warping as shown by data from geodetic triangulation networks and geomorphology, and several major high-angle fault zones are seismically active. These faults continue to acquire displacement both suddenly during earthquakes and slowly by gentle creep with no recordable shocks. Pleistocene beds and terraces at places are steeply warped. Strong deformation occurred during the late Pliocene and early Pleistocene. Most of the Tertiary was characterized by fragmentation of the region into basins and intervening ranges following comparatively more widespread sedimentary transgressions and regressions during the early Tertiary and late Mesozoic. The structural significance and history of the San Andreas fault system are still under study. In central California, Pliocene and Pleistocene sedimentary facies are apparently offset laterally as much as 25 miles, but in this region strike-slip of greater amounts in older rocks has not yet been documented. The San Andreas separates very different terranes, with mismatched stratigraphic sections facing across the fault. These probably can be matched only through recourse to major right-slip, increasing in displacement with age. Right-slip of about 200 miles is reasonably well established in southern California, and such displacements, extended into central and northern California, probably account for the contrast in terranes, including basement. Here the San Andreas separates the Franciscan complex of disturbed graywacke, mudstone, chert, conglomerate, limestone, mafic and ultramafic volcanic rocks and serpentine, and associated metamorphic rocks from the basement of granites and gneiss. The magnitude and timing of displacements on the San Andreas and related faults, which probably originated in the early Tertiary, will only be determined through the mapping and correlating of sedimentary facies that are cut and offset by the fault. As yet this analysis has but barely commenced. The Sierra Nevada and Klamath Mountains were the site of rapid eugeosynclinal sedimentation and volcanism in early Late Jurassic time. These strata were deformed, metamorphosed, faulted, and intruded by serpentine and granitic plutons in turn; all in the mid-Late Jurassic. Following uplift, deep erosion, and subsidence, sedimentation in the latest Jurassic transgressed and overlapped eastward across the ancient Sierran margin. Altogether, 40,000 feet of mudstone, graywacke, and conglomerate were deposited in the Great Valley sequence by the end of the Cretaceous. Beginning also in the early Late Jurassic nearby, but in unclear tectonic relationship to the Great Valley sequence, Franciscan sedimentation, volcanism, and downbuckling carried strata to depths of about 70,000 feet. Here deeper beds were converted to the blueschist metamorphic facies and then rapidly elevated and perhaps in part thrusted in mid-Late Jurassic time. Following continued eugeosynclinal sedimentation, major thrusting or downslope sliding and mixing on a grand scale took place in the Franciscan terrane in the Middle Cretaceous. The complexity of the Franciscan is the consequence of these events together with overprints of Tertiary deformation, which at places also included major thrusting and near isoclinal folding, diapir or piercement structures, limited gravitational sliding, and strong deformation along high-angle shear zones. Ancient and complex rocks of the thick continental crust give way abruptly to the simple, thin, and presumably younger crust beneath the Pacific Ocean. The Moho discontinuity has a depth of about 18 miles (29 km) under the Coast Ranges and rises to about 8 miles (13 km) under the basaltic oceanic crust. Pacific fault zones apparently pass largely beneath, and only slightly disturb, the continental plate. Faults of the San Andreas system probably are mainly confined to the continental plate and may converge and merge to constitute the continental margin

Helicopter low-speed yaw control

A system for improving yaw control at low speeds consists of one strake placed on the upper portion of the fuselage facing the retreating rotor blade and another strake placed on the lower portion of the fuselage facing the advancing rotor blade. These strakes spoil the airflow on the helicopter tail boom during hover, low speed flight, and right or left sidewards flight so that less side thrust is required from the tail rotor

Two-dimensional aerodynamic characteristics of several polygon-shaped cross-sectional models applicable to helicopter fuselages

A wind-tunnel investigation was conducted to determine 2-D aerodynamic characteristics of nine polygon-shaped models applicable to helicopter fuselages. The models varied from 1/2 to 1/5 scale and were nominally triangular, diamond, and rectangular in shape. Side force and normal force were obtained at increments of angle of flow incidence from -45 to 90 degrees. The data were compared with results from a baseline UH-60 tail-boom cross-section model. The results indicate that the overall shapes of the plots of normal force and side force were similar to the characteristic shape of the baseline data; however, there were important differences in magnitude. At a flow incidence of 0 degrees, larger values of normal force for the polygon models indicate an increase in fuselage down load of 1 to 2.5 percent of main-rotor thrust compared with the baseline value. Also, potential was indicated among some of the configurations to produce high fuselage side forces and yawing moments compared with the baseline model

Tryptophan degradation in irritable bowel syndrome: evidence of indoleamine 2,3-dioxygenase activation in a male cohort

<p>Abstract</p> <p>Background</p> <p>Irritable bowel syndrome (IBS) is a common disorder that affects 10–15% of the population. Although characterised by a lack of reliable biological markers, the disease state is increasingly viewed as a disorder of the brain-gut axis. In particular, accumulating evidence points to the involvement of both the central and peripheral serotonergic systems in disease symptomatology. Furthermore, altered tryptophan metabolism and indoleamine 2,3-dioxygenase (IDO) activity are hallmarks of many stress-related disorders. The kynurenine pathway of tryptophan degradation may serve to link these findings to the low level immune activation recently described in IBS. In this study, we investigated tryptophan degradation in a male IBS cohort (n = 10) and control subjects (n = 26).</p> <p>Methods</p> <p>Plasma samples were obtained from patients and healthy controls. Tryptophan and its metabolites were measured by high performance liquid chromatography (HPLC) and neopterin, a sensitive marker of immune activation, was measured using a commercially available ELISA assay.</p> <p>Results</p> <p>Both kynurenine levels and the kynurenine:tryptophan ratio were significantly increased in the IBS cohort compared with healthy controls. Neopterin was also increased in the IBS subjects and the concentration of the neuroprotective metabolite kynurenic acid was decreased, as was the kynurenic acid:kynurenine ratio.</p> <p>Conclusion</p> <p>These findings suggest that the activity of IDO, the immunoresponsive enzyme which is responsible for the degradation of tryptophan along this pathway, is enhanced in IBS patients relative to controls. This study provides novel evidence for an immune-mediated degradation of tryptophan in a male IBS population and identifies the kynurenine pathway as a potential source of biomarkers in this debilitating condition.</p

Molecular engineering improves antigen quality and enables integrated manufacturing of a trivalent subunit vaccine candidate for rotavirus

Background Vaccines comprising recombinant subunit proteins are well-suited to low-cost and high-volume production for global use. The design of manufacturing processes to produce subunit vaccines depends, however, on the inherent biophysical traits presented by an individual antigen of interest. New candidate antigens typically require developing custom processes for each one and may require unique steps to ensure sufficient yields without product-related variants. Results We describe a holistic approach for the molecular design of recombinant protein antigens—considering both their manufacturability and antigenicity—informed by bioinformatic analyses such as RNA-seq, ribosome profiling, and sequence-based prediction tools. We demonstrate this approach by engineering the product sequences of a trivalent non-replicating rotavirus vaccine (NRRV) candidate to improve titers and mitigate product variants caused by N-terminal truncation, hypermannosylation, and aggregation. The three engineered NRRV antigens retained their original antigenicity and immunogenicity, while their improved manufacturability enabled concomitant production and purification of all three serotypes in a single, end-to-end perfusion-based process using the biotechnical yeast Komagataella phaffii. Conclusions This study demonstrates that molecular engineering of subunit antigens using advanced genomic methods can facilitate their manufacturing in continuous production. Such capabilities have potential to lower the cost and volumetric requirements in manufacturing vaccines based on recombinant protein subunits

GO Explorer: A gene-ontology tool to aid in the interpretation of shotgun proteomics data

<p>Abstract</p> <p>Background</p> <p>Spectral counting is a shotgun proteomics approach comprising the identification and relative quantitation of thousands of proteins in complex mixtures. However, this strategy generates bewildering amounts of data whose biological interpretation is a challenge.</p> <p>Results</p> <p>Here we present a new algorithm, termed GO Explorer (GOEx), that leverages the gene ontology (GO) to aid in the interpretation of proteomic data. GOEx stands out because it combines data from protein fold changes with GO over-representation statistics to help draw conclusions. Moreover, it is tightly integrated within the PatternLab for Proteomics project and, thus, lies within a complete computational environment that provides parsers and pattern recognition tools designed for spectral counting. GOEx offers three independent methods to query data: an interactive directed acyclic graph, a specialist mode where key words can be searched, and an automatic search. Its usefulness is demonstrated by applying it to help interpret the effects of perillyl alcohol, a natural chemotherapeutic agent, on glioblastoma multiform cell lines (A172). We used a new multi-surfactant shotgun proteomic strategy and identified more than 2600 proteins; GOEx pinpointed key sets of differentially expressed proteins related to cell cycle, alcohol catabolism, the Ras pathway, apoptosis, and stress response, to name a few.</p> <p>Conclusion</p> <p>GOEx facilitates organism-specific studies by leveraging GO and providing a rich graphical user interface. It is a simple to use tool, specialized for biologists who wish to analyze spectral counting data from shotgun proteomics. GOEx is available at <url>http://pcarvalho.com/patternlab</url>.</p

Guidelines for Genome-Scale Analysis of Biological Rhythms

Genome biology approaches have made enormous contributions to our understanding of biological rhythms, particularly in identifying outputs of the clock, including RNAs, proteins, and metabolites, whose abundance oscillates throughout the day. These methods hold significant promise for future discovery, particularly when combined with computational modeling. However, genome-scale experiments are costly and laborious, yielding “big data” that are conceptually and statistically difficult to analyze. There is no obvious consensus regarding design or analysis. Here we discuss the relevant technical considerations to generate reproducible, statistically sound, and broadly useful genome-scale data. Rather than suggest a set of rigid rules, we aim to codify principles by which investigators, reviewers, and readers of the primary literature can evaluate the suitability of different experimental designs for measuring different aspects of biological rhythms. We introduce CircaInSilico, a web-based application for generating synthetic genome biology data to benchmark statistical methods for studying biological rhythms. Finally, we discuss several unmet analytical needs, including applications to clinical medicine, and suggest productive avenues to address them

Long Beach Earthquake and Protection Against Future Earthquakes -- Summary of Report by Joint Technical Committee on Earthquake Protection, Dr. Robert A. Millikan, Chairman

To the Public of the Pacific Southwest: In response to official requests from many representative technical and civic organizations, the Joint Technical Committee on Earthquake Protection was organized after the earthquake of March 10, 1933 to consider ways and means of minimizing loss of life and property damage in the event of another earthquake of equal or greater intensity. We now present to you, in the form of this summarized report, our belief as to the seismic hazard in this region and our opinion as to the proper balance between the degree of protection to be afforded life and property and the cost of providing such protection. We sincerely hope that the lessons of the Long Beach earthquake will not be forgotten as were the lessons which should have been fixed indelibly in the minds of all by the earthquakes of the past. Joint Technical Committee on Earthquake Protection. Robert A. Millikan, Chairman. June 7-1933

Development and Validation of a Symptom-Based Activity Index for Adults With Eosinophilic Esophagitis

Standardized instruments are needed to assess the activity of eosinophilic esophagitis (EoE), to provide endpoints for clinical trials and observational studies. We aimed to develop and validate a patient-reported outcome (PRO) instrument and score, based on items that could account for variations in patients’ assessments of disease severity. We also evaluated relationships between patients’ assessment of disease severity and EoE-associated endoscopic, histologic, and laboratory findings