Therapeutic Ultrasound as a Potential Male Dog Contraceptive: Determination of the Most Effective Application Protocol

Contents: Ultrasound is one of the most promising forms of non-invasive contraception and has been studied in several animal models. The objective of the current investigation was to determine the most practical and effective application protocol for dog sterilization. A total of 100 dogs were divided into five equal groups. Group A received 5-min applications three times performed at 48-hr intervals and covering the entire testicular area at frequency of 1 MHz; Group B received 5-min applications three times performed at 48-hr intervals over the dorso-cranial area of the testis at frequency of 3 MHz; Group C received three sequential 5-min applications (at 5-min intervals between applications) covering the entire testicular area at frequency of 1 MHz; Group D received 15-min applications two times performed at 48-hr intervals and covering the entire testicular area at frequency of 1 MHz. The experimental groups' ultrasound had an intensity of 1.5W/cm2. The Control Group had the same procedure as Group A, but with the transducer switched-off. Dogs were surgically castrated 40 days following the treatment for histological examination. Azoospermia, testicular volume reduction and apparently irreversible testicular damage were achieved by Group A. No effects were noticed in the other groups. Testosterone levels remained within physiological range with all application protocols. A regimen of three applications of ultrasound at 1 MHz, and 1.5 W/cm2, lasting 5 min with an interval of 48 h was effective as permanent sterilization in the dog without hormonal impact

Ochratoxin A affects oocyte maturation and subsequent embryo developmental dynamics in the juvenile sheep model

The genotoxic and nephrotoxic mycotoxin Ochratoxin A (OTA) has also been reported to have adverse effects on oocyte maturation and embryo development. Previous studies on the effects of OTA on female fertility have used micromolar concentrations, but no information is available to date on effects in a more relevant nanomolar range. This study used a juvenile sheep model to evaluate the effects of oocyte exposure to low levels of OTA on maturation, fertilization, and embryo development. Further, it was investigated whether different mechanisms of action of OTA could be responsible for varying toxic effects at different levels of exposure. Cumulus-oocyte-complexes (COCs) were exposed to 10 μmol/L–0.1 nmol/L OTA during in vitro maturation and evaluated for cumulus viability, oocyte maturation, and bioenergetic/oxidative status. COCs were subjected to in vitro fertilization, embryo culture, and embryo quality assessment via morphology, viability, bioenergetic/oxidative status, and time-lapse monitoring. At micromolar concentrations, OTA induced cytotoxic effects, by reducing cumulus expansion and oocyte maturation. OTA altered temporospatial dynamics of zygote pronuclear formation and embryo morphokinetics. Blastocysts, even morphologically normal, were found to undergo collapse events, which were probably related to boosted blastocyst mitochondrial activity. At nanomolar concentrations, OTA did not affect COC morpho-functional parameters, but impaired oocyte ability to prevent polyspermy and increased blastocyst apoptosis. In conclusion, in the female germ cell, cytotoxic nonspecific effects characterize OTA-induced toxicity at high exposure levels, whereas fine tuning-mode effects, not associated with altered cell viability and integrity, characterize OTA toxic action at low levels

Functional Expression of the Extracellular Calcium Sensing Receptor (CaSR) in Equine Umbilical Cord Matrix Size-Sieved Stem Cells

The present study investigates the effects of high external calcium concentration ([Ca(2+)](o)) and the calcimimetic NPS R-467, a known calcium-sensing receptor (CaSR) agonist, on growth/proliferation of two equine size-sieved umbilical cord matrix mesenchymal stem cell (eUCM-MSC) lines. The involvement of CaSR on observed cell response was analyzed at both the mRNA and protein level.A large (>8 µm in diameter) and a small (<8 µm) cell line were cultured in medium containing: 1) low [Ca(2+)](o) (0.37 mM); 2) high [Ca(2+)](o) (2.87 mM); 3) NPS R-467 (3 µM) in presence of high [Ca(2+)](o) and 4) the CaSR antagonist NPS 2390 (10 µM for 30 min.) followed by incubation in presence of NPS R-467 in medium with high [Ca(2+)](o). Growth/proliferation rates were compared between groups. In large cells, the addition of NPS R-467 significantly increased cell growth whereas increasing [Ca(2+)](o) was not effective in this cell line. In small cells, both higher [Ca(2+)](o) and NPS R-467 increased cell growth. In both cell lines, preincubation with the CaSR antagonist NPS 2390 significantly inhibited the agonistic effect of NPS R-467. In both cell lines, increased [Ca(2+)](o) and/or NPS R-467 reduced doubling time values.Treatment with NPS R-467 down-regulated CaSR mRNA expression in both cell lines. In large cells, NPS R-467 reduced CaSR labeling in the cytosol and increased it at cortical level.In conclusion, calcium and the calcimimetic NPS R-467 reduce CaSR mRNA expression and stimulate cell growth/proliferation in eUCM-MSC. Their use as components of media for eUCM-MSC culture could be beneficial to obtain enough cells for down-stream purposes

Large-scale unit commitment under uncertainty: an updated literature survey

The Unit Commitment problem in energy management aims at finding the optimal production schedule of a set of generation units, while meeting various system-wide constraints. It has always been a large-scale, non-convex, difficult problem, especially in view of the fact that, due to operational requirements, it has to be solved in an unreasonably small time for its size. Recently, growing renewable energy shares have strongly increased the level of uncertainty in the system, making the (ideal) Unit Commitment model a large-scale, non-convex and uncertain (stochastic, robust, chance-constrained) program. We provide a survey of the literature on methods for the Uncertain Unit Commitment problem, in all its variants. We start with a review of the main contributions on solution methods for the deterministic versions of the problem, focussing on those based on mathematical programming techniques that are more relevant for the uncertain versions of the problem. We then present and categorize the approaches to the latter, while providing entry points to the relevant literature on optimization under uncertainty. This is an updated version of the paper "Large-scale Unit Commitment under uncertainty: a literature survey" that appeared in 4OR 13(2), 115--171 (2015); this version has over 170 more citations, most of which appeared in the last three years, proving how fast the literature on uncertain Unit Commitment evolves, and therefore the interest in this subject

Tighter Approximated MILP Formulations for Unit Commitment Problems

The short-term Unit Commitment (UC) problem in hydro-thermal power generation is a large-scale, Mixed-Integer NonLinear Program (MINLP), which is difficult to solve efficiently, especially for large-scale instances. It is possible to approximate the nonlinear objective function of the problem by means of piecewise-linear functions, so that UC can be approximated by a Mixed-Integer Linear Program (MILP); applying the available efficient general-purpose MILP solvers to the resulting formulations, good quality solutions can be obtained in a relatively short amount of time. We build on this approach, presenting a novel way to approximating the nonlinear objective function based on a recently developed class of valid inequalities for the problem, called "Perspective Cuts". At least for many realistic instances of a general basic formulation of UC, a MILP-based heuristic obtains comparable or slightly better solutions in less time when employing the new approach rather than the standard piecewise linearizations, while being not more difficult to implement and use. Furthermore, "dynamic" formulations, whereby the approximation is iteratively improved, provide even better results if the approximation is appropriately controlled

Solving Unit Commitment Problems with General Ramp Contraints

Lagrangian Relaxation (LR) algorithms are among the most successful approaches for solving large-scale hydro-thermal Unit Commitment (UC) problems; this is largely due to the fact that the Single-Unit Commitment (1UC) problems resulting from the decomposition, incorporating many kinds of technical constraints such as minimum up- and down-time requirements and time-dependent startup costs, can be efficiently solved by Dynamic Programming (DP) techniques. Ramp constraints have historically eluded efficient exact DP approaches; however, this has recently changed [A16]. We show that the newly proposed DP algorithm for ramp-constrained (1UC) problems allows to extend existing LR approaches to ramp-constrained (UC); this is not obvious since the heuristic procedures typically used to recover a primal feasible solution are not easily extended to take ramp limits into account. However, dealing with ramp constraints in the subproblems turns out to be sufficient to provide the LR heuristic enough guidance to produce good feasible solutions even with no other modification of the approach; this is due to the fact that (sophisticated) LR algorithms to (UC) duly exploit the primal information computed by the Lagrangian Dual, which in the proposed approach is ramp feasible. We also show by computational experiments that the LR is competitive with those based on general-purpose Mixed-Integer Program (MIP) solvers for large-scale instances, especially hydro-thermal ones

New Lagrangian Heuristics for Ramp-Constrained Unit Commitment Problems

Lagrangian Relaxation (LR) algorithms are among the most successful approaches for solving large-scale hydro-thermal Unit Commitment (UC) problems; this is largely due to the fact that the Single-Unit Commitment (1UC) problems resulting from the decomposition can be efficiently solved by Dynamic Programming (DP) techniques. Ramp constraints have historically eluded efficient exact DP approaches; however, this has recently changed [A16]. We show that the newly proposed DP algorithm for ramp-constrained (1UC) problems, together with a new heuristic phase that explicitly takes into account ramp limits on the maximum and minimum available power at each hour, can reliably find good-quality solutions to even large-scale (UC) instances in short time

Sequential Lagrangian-MILP Approaches for Unit Commitment Problems

The short-term Unit Commitment (UC) problem in hydro-thermal power generation is a fundamental problem in short-term electrical generation scheduling. Historically, Lagrangian techniques have been used to tackle this large-scale, difficult Mixed-Integer NonLinear Program (MINLP); this requires being able to efficiently solve the Lagrangian subproblems, which has only recently become possible (efficiently enough) for units subject to significant ramp constraints. In the last years, alternative approaches have been devised where the nonlinearities in the problem are approximated by means of piecewise-linear functions, so that UC can be approximated by a Mixed-Integer Linear Program (MILP); in particular, using a recently developed class of valid inequalities for the problem, called "Perspective Cuts", significant improvements have been obtained in the efficiency and effectiveness of the solution algorithms. These two different approaches have complementary strengths; Lagrangian ones provide very good lower bounds quickly, but they require sophisticated heuristics—which may need to be changed every time that the mathematical model changes—for producing actual feasible solutions. MILP approaches have been shown to be able to provide very good feasible solutions quickly, but their lower bound is significantly worse. We present a sequential approach which combines the two methods, trying to exploit each one's strengths; we show, by means of extensive computational experiments on realistic instances, that the sequential approach may exhibit significantly better efficiency than either of the two basic ones, depending on the degree of accuracy requested to the feasible solutions