Detrimental effects of uterine disease and lipopolysaccharide on luteal angiogenesis.

Reproductive tract inflammatory disease (RTID) commonly occurs after the traumatic events of parturition and adversely affects follicular function. This study is the first to describe the cellular and steroidogenic characteristics of corpora lutea from cattle with RTID and the effects of pathogen-associated molecular patterns (PAMPs) on luteal angiogenesis and function in vitro. Luteal weight (P < 0.05) and progesterone content (P < 0.05) were reduced (1.2-fold) in cows with RTID, accompanied by reduced CYP11A (P < 0.05), HSD3B (P < 0.01) and STAR (P < 0.01) protein expression. Immunohistochemistry revealed that luteal vascularity (VWF) and pericyte (ACTA2) coverage were >3-fold lower in RTID cows (P < 0.05). To link these observations to bacterial infection and determine specificity of action, a physiologically relevant luteal angiogenesis culture system examined the effects of PAMPs on endothelial cell (EC) network formation and progesterone production, in the presence of pro-angiogenic factors. Luteal EC networks were reduced ≤95% (P < 0.05) by lipopolysaccharide (LPS, toll-like receptor (TLR) 4 agonist) but not by TLR2 agonists lipoteichoic acid or peptidoglycan. Conversely, progesterone production and steroidogenic protein expression were unaffected by PAMPs (P > 0.05). Moreover, the adverse effect of LPS on luteal EC networks was dose-dependent and effective from 1 ng/mL (P < 0.05), while few EC networks were present above 10 ng/mL LPS (P < 0.001). LPS reduced proliferation (P < 0.05) and increased apoptosis of EC (P < 0.001). The specific TLR4 inhibitor TAK242 reversed the effects of LPS on EC networks. In conclusion, luteal vasculature is adversely sensitive to LPS acting via TLR4, therefore ovarian exposure to LPS from any Gram-negative bacterial infection will profoundly influence subsequent reproductive potential.

Evaluation of progestogen supplementation for luteal phase support in fresh in vitro fertilization cycles.

OBJECTIVE: To evaluate the effectiveness of progestogen supplementation in improving clinical pregnancy rates in women undergoing fresh IVF cycles and to compare different routes, start times, durations, and estrogen coadministration regimen. DESIGN: Comprehensive systematic review and meta-analysis. SETTING: University. PATIENT(S): Women undergoing fresh IVF cycles who did and did not receive progestogen supplementation. INTERVENTION(S): Summary odds ratios (ORs) were calculated by binomial logistic regression. MAIN OUTCOME MEASURE(S): Clinical pregnancy rates. RESULT(S): Eighty-two articles (26,726 women) were included. Clinical pregnancy rates were increased by IM (OR = 4.57), vaginal (OR = 3.34), SC (OR = 3.36), or oral (OR = 2.57) progestogen supplementation versus no treatment. The greatest benefit was observed when progestogens were supplemented IM versus vaginally (OR = 1.37). The optimal time to commence administration was between oocyte retrieval and ET (OR = 1.31), with oocyte retrieval +1 day being most beneficial. Coadministration of estrogen had no benefit (OR = 1.33), whether progestogens were coadministered vaginally or IM. Clinical pregnancy rates were equivalent when progestogen supplementation was ceased after ≤3 weeks or continued for up to 12 weeks (OR = 1.06). CONCLUSION(S): This broad-ranging meta-analysis highlights the need to reevaluate current clinical practice. The use of progestogens in fresh IVF cycles is substantially beneficial to clinical pregnancy. Critically, the use of IM progestogens should not be dismissed, as it yielded the greatest clinical pregnancy rates. Pregnancy success was impacted by initiation of therapy, with 1 day after oocyte retrieval being optimal. There is little evidence to support coadministration of estrogen or prolonging progestogen treatment beyond 3 weeks.

Model predictive controller-based spatiotemporal path tracking method for transhumeral prostheses.

BACKGROUND: Transhumeral prostheses are worn by transhumeral amputees to replace the missing upper limb segment between shoulder and elbow. Prostheses should be able to function as a natural limb for the user to gain the full advantage of wearing a prosthesis. When performing reach-to-grasp and pointing motions by the upper limb, the hand is capable of adhering to a straight-line path with a bell-shaped velocity profile. AIM: Aim was to develop a dynamic path-tracking method for transhumeral prostheses to gain the capability of adhering to a straight-line path. METHOD: Proposed method uses model predictive controller (MPC) developed based on the kinematic model of the prosthesis. Moreover, a shoulder matcher is proposed to match actual shoulder pose with the predicted shoulder pose and to select the best joint angles for the prosthesis for a particular instance. Furthermore, the proposed method is capable of dynamically updating the path if the human performs shoulder motions, which are not as planned by the MPC. RESULTS: Several experiments are conducted to validate the proposed method. The proposed method is capable of taking a straight-line path similar to a natural human. CONCLUSION: This paper proposed a dynamic path-tracking method based on a model predictive controller. The proposed method is capable of taking the prosthetic hand on a straight-line path, which is similar to a path taken by a natural human hand.

Physiological responses of cultured bovine granulosa cells to elevated temperatures under low and high oxygen in the presence of different concentrations of melatonin.

Our understanding of the effects of temperature on granulosa cell (GC) physiology is primarily limited to in vitro studies conducted under atmospheric (∼20% O2) conditions. In the current series of factorial experiments we identify important effects of O2 level (i.e. 5% vs 20% O2) on GC viability and steroidogenesis, and go onto report effects of standard (37.5 °C) vs high (40.0 °C) temperatures under more physiologically representative (i.e. 5%) O2 levels in the presence of different levels of melatonin (0, 20, 200 and 2000 pg/ml); a potent free-radical scavenger and abundant molecule within the ovarian follicle. Cells aspirated from antral (4-6 mm) follicles were cultured in fibronectin-coated wells using serum-free M199 for up to 144 h. At 37.5 °C viable cell number was enhanced and luteinization reduced under 5 vs 20% O2. Oxygen level interacted (P < 0.001) with time in culture to affect aromatase activity and cell estradiol (E2) production (pg/mL/105 cells). These decreased between 48 and 96 h for both O2 levels but increased again by 144 h for cells cultured under 5% but not 20% O2. Progesterone (P4) concentration (ng/mL/105 cells) was greater (P < 0.001) under 20 vs 5% O2 at 96 and 144 h. Cell number increased (P < 0.01) with time in culture under 5% O2 irrespective of temperature. However, higher doses of melatonin increased viable cell number at 40.0 °C but reduced viable cell number at 37.5 °C (P = 0.004). Melatonin also reduced (P < 0.001) ROS generation at both O2 levels across all concentrations. E2 increased with time in culture at both temperatures under 5% O2, however P4 declined between 96 and 144 h at 40.0 but not 37.5 °C. Furthermore, melatonin interacted (P < 0.001) with temperature in a dose dependent manner to increase P4 at 37.5 °C but to reduce P4 at 40.0 °C. Transcript expression for HSD3B1 paralleled temporal changes in P4 production, and those for HBA were greater at 5% than 20% O2, suggesting that hemoglobin synthesis is responsive to changes in O2 level. In conclusion, 5% O2 enhances GC proliferation and reduces luteinization. Elevated temperatures under 5% O2 reduce GC proliferation and P4 production. Melatonin reduces ROS generation irrespective of O2 level and temperature, but interacts with temperature in a dose dependent manner to influence GC proliferation and luteinization.

Efficacy of progesterone supplementation during early pregnancy in cows: A meta-analysis.

Progesterone is a critical hormone during early pregnancy in the cow. As a result, a number of studies have investigated the effects of progesterone supplementation on pregnancy rates. In this study, a meta-analysis using a univariate binary random effects model was carried out on 84 specific treatments reported in 53 publications involving control (n = 9905) and progesterone-treated (n = 9135) cows. Although the results of individual studies showed wide variations (-40% to +50% point changes), progesterone treatment resulted in an overall increase in pregnancy rate odds ratio (OR = 1.12; P < 0.01). Improvements in pregnancy rate were only observed in cows treated at natural estrus (OR = 1.41, P < 0.01) and not following synchronization of estrus or ovulation. Although treatment between Days 3 to 7 postinsemination was beneficial (OR = 1.15; P < 0.01), treatment earlier or later than this was not. Progesterone supplementation was beneficial in cows of lower fertility (<45% control pregnancy rate) but not in cows with higher fertility. These results indicated that the benefit of progesterone supplementation on fertility of cows required exogenous progesterone supplementation to start between Day 3 to 7 and the appropriate reproductive status (i.e., lower fertility, natural estrus) of the treated cows.

A retrospective study on changes in residents' physical activities, social interactions, and neighborhood cohesion after moving to a walkable community.

OBJECTIVE: This study is to examine changes in residents' physical activities, social interactions, and neighborhood cohesion after they moved to a walkable community in Austin, Texas. METHODS: Retrospective surveys (N=449) were administered in 2013-2014 to collect pre- and post-move data about the outcome variables and relevant personal, social, and physical environmental factors. Walkability of each resident's pre-move community was measured using the Walk Score. T tests were used to examine the pre-post move differences in the outcomes in the whole sample and across sub-groups with different physical activity levels, neighborhood conditions, and neighborhood preferences before the move. RESULTS: After the move, total physical activity increased significantly in the whole sample and all sub-groups except those who were previously sufficiently active; lived in communities with high walkability, social interactions, or neighborhood cohesion; or had moderate preference for walkable neighborhoods. Walking in the community increased in the whole sample and all subgroups except those who were previously sufficiently active, moved from high-walkability communities, or had little to no preference for walkable neighborhoods. Social interactions and neighborhood cohesion increased significantly after the move in the whole sample and all sub-groups. CONCLUSION: This study explored potential health benefits of a walkable community in promoting physically and socially active lifestyles, especially for populations at higher risk of obesity. The initial result is promising, suggesting the need for more work to further examine the relationships between health and community design using pre-post assessments.

Mathematical analysis of a model for the growth of the bovine corpus luteum.

The corpus luteum (CL) is an ovarian tissue that grows in the wound space created by follicular rupture. It produces the progesterone needed in the uterus to maintain pregnancy. Rapid growth of the CL and progesterone transport to the uterus require angiogenesis, the creation of new blood vessels from pre-existing ones, a process which is regulated by proteins that include fibroblast growth factor 2 (FGF2). In this paper we develop a system of time-dependent ordinary differential equations to model CL growth. The dependent variables represent FGF2, endothelial cells (ECs), luteal cells, and stromal cells (like pericytes), by assuming that the CL volume is a continuum of the three cell types. We assume that if the CL volume exceeds that of the ovulated follicle, then growth is inhibited. This threshold volume partitions the system dynamics into two regimes, so that the model may be classified as a Filippov (piecewise smooth) system. We show that normal CL growth requires an appropriate balance between the growth rates of luteal and stromal cells. We investigate how angiogenesis influences CL growth by considering how the system dynamics depend on the dimensionless EC proliferation rate, ρ5. We find that weak (low ρ5) or strong (high ρ5) angiogenesis leads to 'pathological' CL growth, since the loss of CL constituents compromises progesterone production or delivery. However, for intermediate values of ρ5, normal CL growth is predicted. The implications of these results for cow fertility are also discussed. For example, inadequate angiogenesis has been linked to infertility in dairy cows.

Fibroblast growth factor 2 induces the precocious development of endothelial cell networks in bovine luteinising follicular cells.

The transition from follicle to corpus luteum represents a period of intense angiogenesis; however, the exact roles of angiogenic factors during this time remain to be elucidated. Thus, the roles of vascular endothelial growth factor (VEGF) A, fibroblast growth factor (FGF) 2 and LH in controlling angiogenesis were examined in the present study. A novel serum-free luteinising follicular angiogenesis culture system was developed in which progesterone production increased during the first 5 days and was increased by LH (P<0.01). Blockade of signalling from FGF receptors (SU5402; P<0.001) and, to a lesser extent, VEGF receptors (SU1498; P<0.001) decreased the development of endothelial cell (EC) networks. Conversely, FGF2 dose-dependently (P<0.001) induced the precocious transition of undeveloped EC islands into branched networks associated with a twofold increase in the number of branch points (P<0.001). In contrast, VEGFA had no effect on the area of EC networks or the number of branch points. LH had no effect on the area of EC networks, but it marginally increased the number of branch points (P<0.05) and FGF2 production (P<0.001). Surprisingly, progesterone production was decreased by FGF2 (P<0.01) but only on Day 5 of culture. Progesterone production was increased by SU5402 (P<0.001) and decreased by SU1498 (P<0.001). These results demonstrate that FGF and VEGF receptors play a fundamental role in the formation of luteal EC networks in vitro, which includes a novel role for FGF2 in induction of EC sprouting.

Thermal isomerizations of cis,anti,cis-tricyclo[7.4.0.0(2,8)]tridec-10-ene.

cis,anti,cis-Tricyclo[7.4.0.0(2,8)]tridec-10-ene (13TCT) undergoes [1,3] sigmatropic rearrangements at 315 °C in the gas phase to the si product 1 and to the sr product 2 with si/sr = 2.1. The dominant thermal isomerization process, however, is epimerization at C8 to afford product 3. That stereomutation at C8 occurs 50% faster than the si and sr shifts combined.

Fibroblast growth factor 2 is a key determinant of vascular sprouting during bovine luteal angiogenesis.

Fibroblast growth factor (FGF) 2 and vascular endothelial growth factor (VEGF) A are thought to be key controllers of luteal angiogenesis; however, their precise roles in the regulation and coordination of this complex process remain unknown. Thus, the temporal and spatial patterns of endothelial network formation were determined by culturing mixed cell types from early bovine corpora lutea on fibronectin in the presence of FGF2 and VEGFA (6 h to 9 days). Endothelial cells, as determined by von Willebrand factor immunohistochemistry, initially grew in cell islands (days 0-3), before undergoing a period of vascular sprouting to display a more tubule-like appearance (days 3-6), and after 9 days in culture had formed extensive intricate networks. Mixed populations of luteal cells were treated with SU1498 (VEGF receptor 2 inhibitor) or SU5402 (FGF receptor 1 inhibitor) or control on days 0-3, 3-6 or 6-9 to determine the role of FGF2 and VEGFA during these specific windows. The total area of endothelial cells was unaffected by SU1498 treatment during any window. In contrast, SU5402 treatment caused maximal reduction in the total area of endothelial cell networks on days 3-6 vs controls (mean reduction 81%; P<0.001) during the period of tubule initiation. Moreover, SU5402 treatment on days 3-6 dramatically reduced the total number of branch points (P<0.001) and degree of branching per endothelial cell island (P<0.05) in the absence of changes in mean island area. This suggests that FGF2 is a key determinant of vascular sprouting and hence critical to luteal development.

Behavior coordination of mobile robotics using supervisory control of fuzzy discrete event systems.

In order to incorporate the uncertainty and impreciseness present in real-world event-driven asynchronous systems, fuzzy discrete event systems (DESs) (FDESs) have been proposed as an extension to crisp DESs. In this paper, first, we propose an extension to the supervisory control theory of FDES by redefining fuzzy controllable and uncontrollable events. The proposed supervisor is capable of enabling feasible uncontrollable and controllable events with different possibilities. Then, the extended supervisory control framework of FDES is employed to model and control several navigational tasks of a mobile robot using the behavior-based approach. The robot has limited sensory capabilities, and the navigations have been performed in several unmodeled environments. The reactive and deliberative behaviors of the mobile robotic system are weighted through fuzzy uncontrollable and controllable events, respectively. By employing the proposed supervisory controller, a command-fusion-type behavior coordination is achieved. The observability of fuzzy events is incorporated to represent the sensory imprecision. As a systematic analysis of the system, a fuzzy-state-based controllability measure is introduced. The approach is implemented in both simulation and real time. A performance evaluation is performed to quantitatively estimate the validity of the proposed approach over its counterparts.

"Megatrends" driving healthcare facility design: a look at the major trends that will shape medical facility design.

Changes in medical construction and design are accelerating exponentially, and anyone who can anticipate where these changes are going to happen will be at an advantage. Knowing the "Megatrends" defining and driving the future of healthcare delivery and healthcare facility design will help decision makers anticipate the future.

An object-based visual attention model for robotic applications.

By extending integrated competition hypothesis, this paper presents an object-based visual attention model, which selects one object of interest using low-dimensional features, resulting that visual perception starts from a fast attentional selection procedure. The proposed attention model involves seven modules: learning of object representations stored in a long-term memory (LTM), preattentive processing, top-down biasing, bottom-up competition, mediation between top-down and bottom-up ways, generation of saliency maps, and perceptual completion processing. It works in two phases: learning phase and attending phase. In the learning phase, the corresponding object representation is trained statistically when one object is attended. A dual-coding object representation consisting of local and global codings is proposed. Intensity, color, and orientation features are used to build the local coding, and a contour feature is employed to constitute the global coding. In the attending phase, the model preattentively segments the visual field into discrete proto-objects using Gestalt rules at first. If a task-specific object is given, the model recalls the corresponding representation from LTM and deduces the task-relevant feature(s) to evaluate top-down biases. The mediation between automatic bottom-up competition and conscious top-down biasing is then performed to yield a location-based saliency map. By combination of location-based saliency within each proto-object, the proto-object-based saliency is evaluated. The most salient proto-object is selected for attention, and it is finally put into the perceptual completion processing module to yield a complete object region. This model has been applied into distinct tasks of robots: detection of task-specific stationary and moving objects. Experimental results under different conditions are shown to validate this model.

A probabilistic model of overt visual attention for cognitive robots.

Visual attention is one of the major requirements for a robot to serve as a cognitive companion for human. The robotic visual attention is mostly concerned with overt attention which accompanies head and eye movements of a robot. In this case, each movement of the camera head triggers a number of events, namely transformation of the camera and the image coordinate systems, change of content of the visual field, and partial appearance of the stimuli. All of these events contribute to the reduction in probability of meaningful identification of the next focus of attention. These events are specific to overt attention with head movement and, therefore, their effects are not addressed in the classical models of covert visual attention. This paper proposes a Bayesian model as a robot-centric solution for the overt visual attention problem. The proposed model, while taking inspiration from the primates visual attention mechanism, guides a robot to direct its camera toward behaviorally relevant and/or visually demanding stimuli. A particle filter implementation of this model addresses the challenges involved in overt attention with head movement. Experimental results demonstrate the performance of the proposed model.

FGF2 is crucial for the development of bovine luteal endothelial networks in vitro.

The development of the corpus luteum requires angiogenesis, and involves the complex interplay between factors such as vascular endothelial growth factor A (VEGFA), fibroblast growth factor 2 (FGF2) and platelet-derived growth factor (PDGF). However, the relative role of these factors remains to be elucidated. This study used a new physiologically relevant mixed luteal cell culture system to test the hypotheses that: a) FGF2 and VEGFA are critical for bovine luteal angiogenesis; and b) local luteal PDGF signalling stimulates the formation of endothelial networks. Cells were treated with receptor tyrosine kinase inhibitors against VEGFA (SU1498), FGF2 (SU5402) or PDGF (AG1295) activity. After 9 days in culture, endothelial cells were immunostained for von Willebrand factor (VWF) and quantified by image analysis. Highly organised intricate endothelial networks were formed in the presence of exogenous VEGFA and FGF2. The inhibition of FGF2 activity reduced the total area of VWF staining versus controls (>95%; P<0.001). Inhibition of VEGF and PDGF activity reduced the endothelial network formation by more than 60 and 75% respectively (P<0.05). Progesterone production increased in all treatments from day 1 to 7 (P<0.001), and was unaffected by FGF2 or PDGF receptor kinase inhibition (P>0.05), but was reduced by the VEGF receptor inhibitor on days 5 and 7 (P<0.001). In conclusion, this study confirmed that VEGF signalling regulates both bovine luteal angiogenesis and progesterone production. However, FGF2 was crucial for luteal endothelial network formation. Also, for the first time, this study showed that local luteal PDGF activity regulates bovine luteal endothelial network formation in vitro.

Design and tuning of standard additive model based fuzzy PID controllers for multivariable process systems.

This paper describes a design and two-level tuning method for fuzzy proportional-integral derivative (FPID) controllers for a multivariable process where the fuzzy inference uses the inference of standard additive model. The proposed method can be used for any n x n multi-input-multi-output process and guarantees closed-loop stability. In the two-level tuning scheme, the tuning follows two steps: low-level tuning followed by high-level tuning. The low-level tuning adjusts apparent linear gains, whereas the high-level tuning changes the nonlinearity in the normalized fuzzy output. In this paper, two types of FPID configurations are considered, and their performances are evaluated by using a real-time multizone temperature control problem having a 3 x 3 process system.