Characterization of phthalate presence in cattle environment and its effects on epigenetic markers expression and steroidogenesis in bovine granulosa cells

Farm animals are now more likely to be exposed to environmental pollutants like phthalates as result of intensifying livestock production systems. Phthalate exposure may cause impairments in human and animal health and fertility. However, research into the occurrence of phthalates in cow operations is scarce. Also, studies on the impact of Di-isobutyl phthalate (DIBP) on female fertility are limited in phthalate research. The first project aimed to determine the effects of DIBP in bovine granulosa cells (GC) proliferation, steroidogenesis, and epigenetic and inflammation pathways. Using in vitro cell culture of bovine GC, DIBP treatment at levels detected in human blood (0 ng/mL, 1 ng/mL, 10 ng/mL, 100 ng/mL) combined with hormones that regulate ovarian folliculogenesis: Follicle-Stimulating Hormone (FSH) or FSH + Insulin Growth Factor 1 (IGF1) were tested. Estradiol production was assessed by ELISA, cell proliferation was determined by cell counting, and relative mRNA abundance was evaluated by RT-qPCR. Cell proliferation and estradiol production were not affected by DIBP treatments in combination with FSH or FSH+IGF1. DIBP treatment in combination with FSH+IGF1 decreased mRNA levels of METTL14 (P<0.01), an RNA N6 methyladenosine (m6A) methylation methyltransferase, TRDMT1 (P<0.05), an RNA 5-methylcytosine (m5C) methylation methyltransferase, and ASC (P<0.05), an NLRP3 inflammasome player. These results indicate that DIBP at environmentally relevant doses regulates gene expression of epigenetic and inflammatory pathways but does not alter GC proliferation or steroidogenesis. The second project aimed to characterize the phthalate concentrations on a livestock farm. Phthalate concentrations were measured in alfalfa hay, corn silage, and pasture. Lactating multiparous Angus cows were fed with alfalfa hay or corn silage for 49 hours. Cows were maintained on pasture prior to exposure to other types of feed. Urine and blood samples were collected before and during feedstuff exposure to examine phthalate metabolite levels. Silage presented higher concentrations of Di-ethyl phthalate (DEP), Benzylbutyl phthalate (BBP), and Di-isononyl phthalate (DINP) than pasture and hay (P<0.05), and hay presented higher concentrations of Di-n-octyl phthalate (DOP) and DINP than pasture (P<0.05). During the trial, hay-fed group had higher urine concentrations of Mono-isobutyl phthalate (MIBP), Mono-n-butyl phthalate (MBP), Mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP), Mono-2-ethylhexyl terephthalate (MEHtP) compared with silage-fed group (P<0.05), and silage fed group had higher urine concentrations of Mono-n-pentyl phthalate (MPP), Mono-cyclohexyl phthalate (MCHP), Mono-2-ethylhexyl phthalate (MEHP), Mono-isononyl phthalate (MINP) (P<0.05). Urine concentrations of MCHP and Mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) were higher in silage-fed group at the end of the trial compared with prior to the start of the trial (P<0.05). Urine concentrations of MIBP and MEOHP were higher in hay fed group at the end of the trial compared with prior to the start of the trial (P<0.05). No differences in plasma phthalate metabolite concentrations were found between hay-fed group and silage-fed group after 49 hours of feeding. However, because Mono-benzyl phthalate (MBzP) had the highest plasma concentrations, it was selected to determine its effects on in vitro cultured bovine GC function. Bovine GC were treated with MBzP at concentrations found in the plasma in the animal trial combined with FSH+IGF1. Bovine GC steroidogenesis or proliferation were not affected by MBzP treatments. The findings demonstrated that silage and, to a lesser extent, hay are possible sources of phthalate exposure for cattle and that feeding them silage or hay resulted in greater amounts of several phthalates. Taken together, these studies reinforce the importance of monitoring environmental contaminants in livestock production and assessing the effects of phthalates at environmentally relevant doses on human and animal reproduction

Investigating the Dynamics and Fragmentation of Nitroaromatic Radical Cations Through Femtosecond Time-Resolved Mass Spectrometry and Computational Chemistry

Chemists have sought to control molecular dissociation with lasers for decades. Effective control of unimolecular dissociation was only achieved with the development of high-intensity ultrashort pulsed lasers and coherent control techniques that operate on timescales faster than vibrational energy redistribution. In view of this, our lab has specialized in the study of polyatomic radical cations using femtosecond time-resolved mass spectrometry (FTRMS). The interest in radical cations stems from the fact that they are highly reactive species that contribute to many physical, chemical, and biological processes. For instance, radical cations participate in shock initiation of detonated energetic materials used as explosives and propellants. In this regard, we have studied some nitroaromatic radical cations commonly used as models for energetic materials. We discuss some results involving the dynamics of vibrational wave packets and rearrangement/fragmentation pathways. Concerning vibrational wave packet dynamics, we employed computational chemistry to predict the most efficient probe wavelength for our experimental measurements on nitrobenzene cation demonstrating the feasibility and convenience of this approach. We also investigated pump-probe control schemes to manipulate fragmentation product yields in p-nitrotoluene (PNT) cation. Finally, we investigated the dissociation dynamics and fragmentation pathways of o-nitroaniline, a model compound for the military explosive 2,4,6-triamino-1,3,5-trinitrobenzene (TATB). This model seems to capture the hydrogen bonding features that lead to energetically unfavorable rearrangement/fragmentation pathways in TATB. We expect that our experimental and computational results provide insights into the inherent stability of this molecule that explains the low sensitivity (and therefore relatively high safety) of TATB as an explosive

Train Timetable Design for Shared Railway Systems using a Linear Programming Approach to Approximate Dynamic Programming

In the last 15 years, the use of rail infrastructure by different train operating companies (shared railway system) has been proposed as a way to improve infrastructure utilization and to increase efficiency in the railway industry. Shared use requires coordination between the infrastructure manager and multiple train operators in a competitive framework, so that regulators must design appropriate capacity pricing and allocation mechanisms. However, the resulting capacity utilization from a given mechanism in the railway industry cannot be known in the absence of operations. Therefore assessment of capacity requires the determination of the train timetable, which eliminates any potential conflicts in bids from the operators. Although there is a broad literature that proposes train timetabling methods for railway systems with single operators, there are few models for shared competitive railway systems. This paper proposes a train timetabling model for shared railway systems that explicitly considers network effects and the existence of multiple operators requesting to operate several types of trains traveling along different routes in the network. The model is formulated and solved both as a mixed integer linear programming (MILP) problem (using a commercial solver) and as a dynamic programming (DP) problem. We solve the DP formulation with a novel algorithm based on a linear programming (LP) approach to approximate dynamic programming (ADP) that can solve much larger problems than are computationally intractable with commercial MILP solvers. The model simulates the optimal decisions by an infrastructure manager for a shared railway system with respect to a given objective function and safety constraints. This model can be used to evaluate alternative capacity pricing and allocation mechanism. We demonstrate the method for one possible capacity pricing and allocation mechanism, and show how the competing demands and the decisions of the infrastructure manager under this mechanism impact the operations on a shared railway system for all stakeholders

An approximate dynamic programming approach for designing train timetables

Traditional approaches to solving the train timetabling problem—the optimal allocation of when each train arrives and departs each station—have relied on Mixed-Integer Programming (MIP) approaches. We propose an alternative formulation for this problem based on the modeling and algorithmic framework of approximate dynamic programming. We present a Q-learning algorithm in order to tractably solve the high-dimensional problem. We compare the performance of several variants of this approach, including discretizing the state and the action spaces, and continuous function approximation with global basis functions. We demonstrate the algorithms on two railway system cases, one minimizing energy consumption subject to punctuality constraints, and one maximizing capacity subject to safety constraints. We demonstrate that the ADP algorithm converges rapidly to an optimal solution, and that the number of iterations required increases linearly in the size of the rail system, in contrast with MIP approaches whose computation time grows exponentially. We also show that an additional benefit to the ADP approach is the intuition gained from visualizing the Q-factor functions, which graphically capture the intuitive tradeoffs between efficiency and constraints in both examples

Analysis of very-high surface area 3D-printed media in a moving bed biofilm reactor for wastewater treatment

Moving Bed Biofilm Reactors (MBBRs) can efficiently treat wastewater by incorporating suspended biocarriers that provide attachment surfaces for active microorganisms. The performance of MBBRs for wastewater treatment is, among other factors, contingent upon the characteristics of the surface area of the biocarriers. Thus, novel biocarrier topology designs can potentially increase MBBR performance in a significant manner. The goal of this work is to assess the performance of 3-D-printed biofilter media biocarriers with varying surface area designs for use in nitrifying MBBRs for wastewater treatment. Mathematical models, rendering, and 3D printing were used to design and fabricate gyroid-shaped biocarriers with a high degree of complexity at three different levels of specific surface area (SSA), generally providing greater specific surface areas than currently available commercial designs. The biocarriers were inoculated with a nitrifying bacteria community, and tested in a series of batch reactors for ammonia conversion to nitrate, in three different experimental configurations: constant fill ratio, constant total surface area, and constant biocarrier media count. Results showed that large and medium SSA gyroid biocarriers delivered the best ammonia conversion performance of all designs, and significantly better than that of a standard commercial design. The percentage of ammonia nitrogen conversion at 8 hours for the best performing biocarrier design was: 99.33% (large SSA gyroid, constant fill ratio), 94.74% (medium SSA gyroid, constant total surface area), and 92.73% (large SSA gyroid, constant biocarrier media count). Additionally, it is shown that the ammonia conversion performance was correlated to the specific surface area of the biocarrier, with the greatest rates of ammonia conversion (99.33%) and nitrate production (2.7 mg/L) for manufactured gyroid biocarriers with a specific surface area greater than 1980.5 m2/m3. The results suggest that the performance of commercial MBBRs for wastewater treatment can be greatly improved by manipulation of media design through topology optimization

Modeling slow deformation of polygonal particles using DEM

We introduce two improvements in the numerical scheme to simulate collision and slow shearing of irregular particles. First, we propose an alternative approach based on simple relations to compute the frictional contact forces. The approach improves efficiency and accuracy of the Discrete Element Method (DEM) when modeling the dynamics of the granular packing. We determine the proper upper limit for the integration step in the standard numerical scheme using a wide range of material parameters. To this end, we study the kinetic energy decay in a stress controlled test between two particles. Second, we show that the usual way of defining the contact plane between two polygonal particles is, in general, not unique which leads to discontinuities in the direction of the contact plane while particles move. To solve this drawback, we introduce an accurate definition for the contact plane based on the shape of the overlap area between touching particles, which evolves continuously in time.Comment: 15 pages, 10 figure

Rail Infrastructure Manager Problem: Analyzing Capacity Pricing and Allocation in Shared Railway System

This paper proposes a train timetabling model for shared railway systems. The model is formulated as a mixed integer linear programming problem and solved both using commercial software and a novel algorithm based on approximate dynamic programming. The results of the train timetabling model can be used to simulate and evaluate the behavior of the infrastructure manager in shared railway systems under different capacity pricing and allocation mechanisms. This would allow regulators and decision makers to identify the implications of these mechanisms for different stakeholders considering the specific characteristics of the system

The MESS of the CMB

We analyze cosmic microwave background (CMB) data taking into account the effects of a momentum dependent effective sound speed (MESS). This approach allows to study the effects of primordial entropy in a model independent way, and its implementation requires a minimal modification of existing CMB fitting numerical codes developed for single scalar field models. We adopt a phenomenological approach, and study the effects a local variation of the MESS around the scale where other analysis have shown some deviation from an approximately scale invariant curvature perturbation spectrum. We obtain a substantial improvement of the fit with respect to a model without MESS, showing that primordial entropy modeled by MESS can be an explanation of these deviations.Comment: 15 pages, 5 figure