Cell-to-Cell Stochastic Variation in Gene Expression Is a Complex Genetic Trait

The genetic control of common traits is rarely deterministic, with many genes contributing only to the chance of developing a given phenotype. This incomplete penetrance is poorly understood and is usually attributed to interactions between genes or interactions between genes and environmental conditions. Because many traits such as cancer can emerge from rare events happening in one or very few cells, we speculate an alternative and complementary possibility where some genotypes could facilitate these events by increasing stochastic cell-to-cell variations (or ‘noise’). As a very first step towards investigating this possibility, we studied how natural genetic variation influences the level of noise in the expression of a single gene using the yeast S. cerevisiae as a model system. Reproducible differences in noise were observed between divergent genetic backgrounds. We found that noise was highly heritable and placed under a complex genetic control. Scanning the genome, we mapped three Quantitative Trait Loci (QTL) of noise, one locus being explained by an increase in noise when transcriptional elongation was impaired. Our results suggest that the level of stochasticity in particular molecular regulations may differ between multicellular individuals depending on their genotypic background. The complex genetic architecture of noise buffering couples genetic to non-genetic robustness and provides a molecular basis to the probabilistic nature of complex traits

Fecal microbiota and bile acid interactions with systemic and adipose tissue metabolism in diet-induced weight loss of obese postmenopausal women

Microbiota and bile acids in the gastrointestinal tract profoundly alter systemic metabolic processes. In obese subjects, gradual weight loss ameliorates adipose tissue inflammation and related systemic changes. We assessed how rapid weight loss due to a very low calorie diet (VLCD) affects the fecal microbiome and fecal bile acid composition, and their interactions with the plasma metabolome and subcutaneous adipose tissue inflammation in obesity. We performed a prospective cohort study of VLCD-induced weight loss of 10% in ten grades 2-3 obese postmenopausal women in a metabolic unit. Baseline and post weight loss evaluation included fasting plasma analyzed by mass spectrometry, adipose tissue transcription by RNA sequencing, stool 16S rRNA sequencing for fecal microbiota, fecal bile acids by mass spectrometry, and urinary metabolic phenotyping by H-NMR spectroscopy. Outcome measures included mixed model correlations between changes in fecal microbiota and bile acid composition with changes in plasma metabolite and adipose tissue gene expression pathways. Alterations in the urinary metabolic phenotype following VLCD-induced weight loss were consistent with starvation ketosis, protein sparing, and disruptions to the functional status of the gut microbiota. We show that the core microbiome was preserved during VLCD-induced weight loss, but with changes in several groups of bacterial taxa with functional implications. UniFrac analysis showed overall parallel shifts in community structure, corresponding to reduced abundance of the genus Roseburia and increased Christensenellaceae;g__ (unknown genus). Imputed microbial functions showed changes in fat and carbohydrate metabolism. A significant fall in fecal total bile acid concentration and reduced deconjugation and 7-α-dihydroxylation were accompanied by significant changes in several bacterial taxa. Individual bile acids in feces correlated with amino acid, purine, and lipid metabolic pathways in plasma. Furthermore, several fecal bile acids and bacterial species correlated with altered gene expression pathways in adipose tissue. VLCD dietary intervention in obese women changed the composition of several fecal microbial populations while preserving the core fecal microbiome. Changes in individual microbial taxa and their functions correlated with variations in the plasma metabolome, fecal bile acid composition, and adipose tissue transcriptome

Design for Entrance Channel Navigation Improvements, Morro Bay Harbor, Morro Bay, California

Source: https://erdc-library.erdc.dren.mil/jspui/A 1:90 scale, three-dimensional hydraulic model was used to investigate the design of proposed entrance channel depth modifications at Morro Bay Harbor, California, with respect to navigation conditions. The impact that the proposed depth changes may have on wave conditions at the existing structures and the spit between the south structures also was addressed, and sediment tracer patterns were obtained in the entrance. The model reproduced the harbor entrance, approximately 7,000 ft of the California shoreline, and offshore bathymetry in the Pacific Ocean to a depth of 60 ft mean lower low water (mllw). A 60-ft-long unidirectional, spectral wave generator, an automated data acquisition system, and crushed coal tracer material were utilized in model operation. It was concluded from test results that: (a.) For the existing harbor entrance, operational waves (8 to 16 ft in height) from the predominant 275 deg direction resulted in hazardous entrance navigation conditions due to wave steepening and/ or breaking. (b.) For the originally proposed improvement plan (Plan 1), navigation conditions in the entrance were improved for operational waves from 275 deg; however, the plan resulted in significantly increased wave heights which may cause damage to the head of the south breakwater during extreme wave conditions (waves ranging from 21 to 30 ft in height). (c.) Of the improvement plans tested, the channel and sand trap configuration of Plan 14 appeared to be optimal with respect to all wave conditions from all directions. Navigation conditions in the entrance will be improved, and the plan will have no negative impact on the existing structures or the spit between the south breakwater and the groin. (d.) Sediment tracer tests indicated that sediment moving in the predominant northerly direction will deposit in the deepened entrance channel and sand trap area of Plan 14 as desired, and material moving in the southerly direction will deposit in the deepened entrance channel. (e.) The -30-ft entrance channel of Plan 15 will result in similar wave conditions for operational and extreme waves as the -40-ft channel of Plan 14, which would be acceptable with regard to entrance conditions and would have no negative impact on the breakwaters and spit area

Ventura Harbor, California, Design for Wave and Shoaling Protection: Coastal Model Investigation

Source: https://erdc-library.erdc.dren.mil/jspui/A 1:75 scale, three-dimensional hydraulic model was used to investigate the design of proposed harbor structures and channel modifications at Ventura Harbor, California, with respect to wave and shoaling conditions in the harbor entrance. The model reproduced approximately 9,400 ft of the California shoreline and included portions of the existing harbor and offshore bathymetry in the Pacific Ocean to a depth of -40 ft mean lower low water (mllw). Improvement plans consisted of a seaward extension of the detached breakwater, the installation of spur groins on the north jetty, construction of a new groin south of the south jetty, and modifications to the entrance channel. An 80-ft-long unidirectional, spectral wave generator, an automated data acquisition system, and a crushed coal tracer material were used in model operation.United States. Army. Corps of Engineers. Los Angeles District

Design for Small-Boat Harbor Improvements, Port Washington Harbor, Wisconsin: Hydraulic Model Investigation

Source: https://erdc-library.erdc.dren.mil/jspui/A 1:75-scale undistor ted hydraulic model reproducing Port Washington Harbor, approximately 2600 ft of shoreline on each side of the harbor, and sufficient offshore area n Lake Michigan to permit generation of the required test waves was used to investigate the design of certain proposed improvements with respect to wave action. The proposed improvement plan consisted of (a) new rubble-mound breakwaters within the existing harbor aggregating about 1330 ft in length and arranged to form a protected harbor of approximately 13.5 acres; (b) a 10-ft-deep, 150-ft-wide entrance channel; (c) a 10-ft-deep anchorage-maneuvering area about 3.5 acres in extent; (d) an 8-ft-deep, 72-ft-wide launching ramp channel extending from the anchorage-manuevering area to a launching ramp; (e) a 500-ft-long wave absorber adjacent to the existing north breakwater; and (f) safety railings on the new breakwaters. A 50-ft-long wave generator, a centrifugal pump and flow meter, and an Automated Data Acquisition and Control System were utilized in model operation. It was concluded from test results that: (1.) Existing conditions are characterized by very rough and turbulent waves in the vicinity of the proposed harbor during periods of severe wave attack. (2.) The proposed improvement plan (plan 1) was considered inadequate in that wave heights exceeded the established wave-height criteria (a maximum of 2.0 ft in the turning basin and 1.0 ft in the mooring area) for all directions due to overtopping of the existing north breakwater and overtopping of the transmission through the proposed east and west breakwaters. (3.) Of the improvement plans tested involving modifications to the north breakwater (adjacent to the proposed harbor), the concrete parapet wall (elevation of +12 ft lwd) in conjunction with wave absorber inside the breakwater (elevation of +4 ft lwd and 6 ft berm width) was determined to be optimal, considering wave protection afforded and cost. (4.) To achieve the established wave-height criteria in the proposed smallboat harbor, it was determined that the crown elevations of the east and west breakwaters must be raised and/or an impervious center must be added. (5.) Rubble- mound breakwater heads (plan 3) will reduce wave heights in the proposed small-boat harbor entrance somewhat; however, increasing the width of the entrance from 150 to 200 ft (plan 4) will increase wave heights in the entrance significantly. (6.) The zigzag west breakwater alignment (plan 7A) resulted in smaller wave heights at the coal wharf (S 37°10'E direction) than did the straight west breakwater alignments (plans 6 and 8); however, maximum wave heights obtained at the coal wharf for plans 6 and 8 were comparable to those obtained for existing conditions, considering all directions tested. (7.) Removal of 185 ft from the shore end of the west breakwater (plan 8) will improve wave-induced circulation without increasing wave heights in the proposed small- boat harbor. (8.) Construction of the proposed small-boat harbor will have no adverse effects on the existing inner slips of the harbor. (9.) Filling in approximately one third of the existing north slip (as requested by the city of Port Washington) (plan 9) will result in increased standing wave heights in the north slip. (10.) The proposed small-boat harbor had no adverse effect on the circulation patterns from the Wisconsin Power and Electric Company water discharge, and the warm water discharge did not enter the proposed small-boat basin to any appreciable extent for the proposed improvement plans._x000D_ _x000D_ NOTE: This file is large. Allow your browser several minutes to download the file

Impact of I-664 Bridge/Tunnel Project on Wave Conditions at Newport News Harbor, Virginia: Hydraulic Model Investigation

Source: https://erdc-library.erdc.dren.mil/jspui/A 1:75- scale undistorted hydraulic model was used to investigate the impacts of the proposed Interstate 664 bridge/tunnel project on wave conditions in Newport News Harbor, Virginia. The model included the harbor, approximately 5600 ft of shoreline adjacent to the harbor entrance, and sufficient offshore area in Hampton Roads to permit generation of the required test waves. Various plans of improvement included the use of either rubble-mound or cellular concrete breakwaters. A 50-ft-long wave generator and an automated data acquisition and control system were utilized in model operation. It was concluded from test results that: (a.) Wave conditions in the existing harbor were relatively calm for storm waves from the various test directions. Only the most severe storm waves (50-year recurrence) from 215, 180, and 70 degrees resulted in wave heights in excess of 1.0 ft in the harbor. (b.) The most critical direction of wave attack for existing conditions was from 215 degrees since the harbor entrance is more directly exposed to incoming waves from this direction . Wave heights ranging from 1.4 to 2.0 ft may occur for severe storm waves (50-year recurrence) from this direction. (c.) The original rubble-mound jetty plan (Plan 1) resulted in wave heights in the harbor well below those obtained for existing conditions. (Maximum wave heights of only 0.9 ft occurred for 50-year storm wave conditions.) (d.) The originally proposed rubble-mound jetty can be reduced 300 ft in length to 925 ft (Plan 10) with no adverse effects on wave conditions in the harbor as a result of installation of the north tunnel island and the relocation of the harbor entrance. (e.) The crest el of the originally proposed rubble-mound jetty can be reduced by 3 ft in height to +9.3 ft with no adverse effects on wave conditions in the harbor. (f.) The original concrete-pile jetty plan (Plan 11) resulted in excessive wave heights (greater than 2 ft) inside the harbor. (g·) By sealing the openings between the 54-in. concrete piles (for a distance of 1035 ft) to an el of -4.7 ft (Plan 12), wave heights in the harbor were comparable to those obtained for existing conditions. Plan 12 resulted in no adverse effects on wave conditions in the harbor as a result of the installation of the north tunnel island and relocation of the harbor entrance and was considered the optimum concrete-pile jetty plan tested with respect to wave protection and economics. (h.) Even though Plan 12 was considered the optimum concrete- pile jetty in regard to impacts on the harbor, wave heights in the new basin formed by the jetties exceeded 3 ft. By completely sealing the openings between the concrete piles for its entire 2710-ft length (Plan 15) wave heights were reduced to 1.3 ft

San Juan National Historic Site, San Juan, Puerto Rico, Design for Prevention of Wave-Induced Erosion: Hydraulic Model Investigation

Source: https://erdc-library.erdc.dren.mil/jspui/A 1:75-scale (undistorted) hydraulic model of the San Juan National Historic Site, which included the entire historic site, the entrance to San Juan Harbor, part of Isla de Cabras, and sufficient offshore area in the Atlantic Ocean to permit generation of the required test waves, was used to investigate the effects of proposed structures on wave attack at the historic site. Proposed improvement plans consisted of the installation of rubble-mound revetments and/or breakwaters on both the ocean and bay sides of El Morro castle. A 90-ft-long wave generator and an automated data acquisition and control system (ADACS) were utilized in model operation. It was concluded from model test results that: (A.) Existing conditions are characterized by very rough and turbulent wave conditions along the San Juan National Historic Site during periods of moderate to large wave attack. (B.) Tests involving the revetment plan (Plan 1) indicated that a 15-ft high revetment was the optimum with respect to wave runup data obtained (i.e. maximum runup came to the top of the revetment but did not overtop in most cases). (C.) Of the improvement plans involving a shore-connected breakwater (Plans 2-2G), it was determined that increasing the width or raising the seaward edge of the breakwater, to achieve the wave-runup criteria, would require a significantly larger volume of rock than would the other plans tested. (D.) Of the improvement plans involving an offshore breakwater north of El Morro and around El Morro point (Plans 3-3D), it was determined that at least a 6-ft breakwater crest elevation (Plan 3D) was required to maintain an average runup value at the shoreline of less than 5 ft (original runup criterion). (E.) Of the improvement plans involving a 15-ft-high revetment and a breakwater north of El Morro (Plans 4-4B), it was determined that the revetment elevation could be reduced in the lee of the breakwater based on the maximum runup obtained for the corresponding plan. (F.) Of the improvement plans involving an offshore breakwater north of El Morro and around the point with a transition to a 15-ft-high west shore revetment (Plans 5-5C), it was determined that a 5.5-ft breakwater crest elevation (Plan 5C) resulted in average runup at the point of 5.2 ft (slightly above the original 5.0-ft criterion). (G.) Of the improvement plans involving an offshore breakwater extending around the point and to the west and north of El Morro with no revetment (Plans 6-6B), it was determined that an 8-ft breakwater crest elevation (Plan 6B) would most nearly meet the desired criterion of 5.0 ft (average wave runup was 5.5 ft at the point). (H.) Of the improvement plans involving an offshore breakwater in conjunction with a revetment at the shoreline north of El Morro and around the point and a west shore revetment (Plans 7A-7D), it was determined that either Plan 7A or 7B would be effective in reducing wave runup to an acceptable level (considering the revised wave runup criterion of 10 ft north of El Morro and westward around the point). (I.) The removal of 161 ft of structure from the eastern end of the offshore breakwater (Plan 7D) will result in wave runup within the revised criterion (12 ft) at the shoreline behind the removed structure. (J.) The installation of any of the major improvement plans tested should have no adverse effect on waves in the entrance to San Juan Bay or on currents around El Morro Castle._x000D_ _x000D_ NOTE: This file is large. Allow your browser several minutes to download the file

Physical Modeling of Small-Boat Harbors: Design Experience, Lessons Learned, and Modeling Guidelines

Source: https://erdc-library.erdc.dren.mil/jspui/This report summarizes the knowledge and insight gained on small-boat harbor design through years of physical model investigations conducted at the US Army Engineer Waterways Experiment Station. An inventory of physically modeled, small-boat harbor projects has been complied and reviewed. Smallboat harbors modeled and subsequently constructed in the prototype, also have been identified. Site specific performance of these projects has been reviewed to determine if the designs recommended in the model investigations were built as recommended and if they have functioned successfully in the prototype. These reviews and study efforts have resulted in a summary of lessons learned through physical modeling of small-boat harbors and site specific performance in the prototype. Types of small-boat harbors and typical problems, physical modeling in general, and physical modeling guidelines also are included in this report

Seabrook Lock Complex, Lake Pontchartrain, Louisiana: Design for Wave Protection at a Temporary Entrance during Various Phases of Lock Construction: Hydraulic Model Investigation

Source: https://erdc-library.erdc.dren.mil/jspui/A 1:36-scale undistorted hydraulic model reproducing the site of the proposed Seabrook Lock Complex, the Inner Harbor Navigation Canal at its junction with Lake Pontchartrain, portions of the New Orleans Lakefront Airport, the stepped seawall adjacent to Lakeshore Drive, and sufficient offshore area in Lake Pontchartrain to permit generation of the required test waves was used to investigate the design of proposed breakwaters with respect to wave action. The proposed breakwater plans involved the placement of sheet-pile and floating structures arranged to provide wave protection to a temporary entrance during various phases of lock construction. An 80-ft-long wave generator and an Automated Data Acquisition and Control System (ADACS) were utilized in model operation. It was concluded from test results that : (A.) With no breakwater protection, the temporary entrances of Construction Sequence Phases II, III, and IV (Plans II, III, and IV) into the Inner Harbor Navigation Canal were characterized by rough and turbulent wave conditions (wave heights in excess of 6 ft) for the waves tested, and the cofferdams for each Construction Sequence Phase were significantly overtopped. (B.) Installation of a 2,150-ft-long sheet-pile breakwater lakeward of the proposed lock site (plans II-A, III-A, and IV-A) will reduce wave heights in the respective temporary entrances of Phases II, III, and IV to within the established 2.0-ft wave-height criterion for test waves from the following directions : (1) Construction Sequence Phase II - NNW (2) Construction Sequence Phase III - N, NNW (3) Construction Sequence Phase IV - N, NNW (C.) In addition to the 2,150-ft-long sheet-pile breakwater of Plan II-A, a 288-ft-long floating breakwater (plan II-C) installed NE of the proposed lock site is required to meet the established wave-height criterion in the temporary entrance of Construction Sequence Phase II for test waves from N. (D.) In addition to the 2,150-ft-long sheet-pile breakwater of Plans II-A, III-A, and IV-A, a 1,344-ft-long floating breakwater (plans 11-D, III-B, and IV-C) installed NW of the proposed lock site is required to meet the established wave-height criterion in the respective temporary entrances of Construction Sequence Phases II, III, and IV for test waves from NW. (E.) The 2,150-ft-long sheet pile breakwater of Plans II-A, III-A, and IV-A, in conjunction with the 1,344-ft-long floating breakwater (plans II-D, III-B, and IV-c), will substantially reduce overtopping of the cofferdams for Construction Sequence Phases II, III, and IV for test waves from all directions

Igloo Wave Absorber Tests for Port Washington Harbor, Wisconsin: Hydraulic Model Investigation

Source: https://erdc-library.erdc.dren.mil/jspui/Port Washington Harbor is exposed to waves generated by storms from northeast to south-southeast. Storm waves from these directions have caused damage to harbor facilities and boats and difficulties to ships and craft navigating the harbor entrance. Standing waves in the slip areas have reached heights of 12 ft. Anchorage in the outer harbor is not safe for small boats due to lack of adequate wave protection. Hence, the harbor is unsafe as a harbor-of-refuge. Consequently, there is no harbor-of-refuge between Milwaukee and Sheboygan, a distance of 56 miles. Also, Port Washington Harbor does not have adequately protected permanent mooring and docking facilities to accommodate the demand for such facilities in this area. Hydraulic model tests were conducted to determine the effects of installation of Igloo wave absorber units in the harbor. Conclusions drawn from the results of these tests were that (A.) Igloo wave absorber units placed in and around the slip areas will significantly reduce wave heights in the slips; (B.) east and west breakwaters constructed of Igloo units without backing will not be stable; (C.) a 500-ft-long Igloo structure adjacent to the nort h breakwater as an alternative to the east breakwater will not meet established wave-height criteria; and (D.) a 200-ft-long Igloo east breakwater (with backing) will meet the established \vave-height criteria