The effects of an environmentally relevant phthalate mixture on female reproduction

Phthalates are a category of chemicals that are commonly used in a wide range of consumer products, including plastics, building materials, medical devices, and personal care products. As a result, humans and animals are constantly exposed to phthalates daily. Metabolites of multiple phthalates frequently have been detected in human urine and blood samples, suggesting ubiquitous exposure to different phthalates. Studies have shown that women are exposed to phthalates at higher levels compared to men, likely due to the higher use of products by women compared to men. This ubiquitous exposure to phthalates is of great concern because several phthalates have been shown to have endocrine disrupting abilities. The developing ovary is thought to be extremely vulnerable to toxicants. In mammals, females are born with a finite pool of primordial follicles, and the size of primordial follicle pool determines the reproductive lifespan. To form the finite pool of primordial follicles, germ cells must undergo mitosis, formation of germ cell nests, meiosis, and germ cell nest breakdown. Any disruption in the formation of the primordial follicle pool can affect female reproductive ability. In the mouse, the ovaries begin to develop around embryonic day (E) 10.5 and the pool of primordial follicles starts to form around birth. During the reproductive life span, some primordial follicles grow into primary follicles, then pre-antral follicles, and subsequently into antral follicles. The antral follicle is the major follicle type that is capable releasing an egg for fertilization and synthesizing sex steroid hormones such as estrogens. Thus, female fertility depends on normal prenatal ovarian development, the maintenance of a constant stream of growing follicles from the primordial to antral stage postnatally, and the health of antral follicles. Chemicals that interfere with developing ovaries, formation of a normal number of primordial follicles, and the quality of antral follicles will cause infertility. Very limited information is available on the effects of phthalate mixtures on female reproduction, and even less information is available on the effects of an environmentally relevant phthalate mixture on female reproduction. Thus, the goal of my doctoral dissertation work was to examine the effects of an environmentally relevant phthalate mixture on female reproduction. Specifically, I examined the direct effect of in vitro phthalate mixture exposure on mouse antral follicles. Further, I examined the effects of in vivo prenatal phthalate mixture exposure on the first and subsequent generation of mice in a transgenerational study design. First, I tested the hypothesis that phthalate mixture exposure decreases antral follicle growth, compromises steroidogenic capacity, and induces atresia. Normal antral follicle growth, steroidogenic capacity, intact oocyte and somatic cells, and undisrupted cell cycles are important for female reproductive health and fertility. I found that the phthalate mixture decreased antral follicle growth starting at 24 hours compared to controls. The mixture also decreased several hormone levels in the steroidogenic pathway compared to control. Further, the mixture reduced atresia rating, but it induced more oocyte fragmentation compared to control. Additionally, the phthalate mixture adversely affected antioxidant enzymes, apoptotic factors, steroidogenic enzymes, and receptors. Interestingly, the mixture adversely affected several cell cycle regulators to induce cell cycle arrest, which in turn reduced atresia. Next, I tested the hypothesis that prenatal exposure to an environmentally relevant phthalate mixture adversely affects female reproduction in mice. Developing sex organs are very sensitive to chemical challenges. For example, prenatal exposure to several phthalates induces “phthalate syndrome” in male rodents to disrupt male reproduction. Similar in females, disrupting the developing female reproductive organs can result in disrupted puberty, irregular cyclicity, subfertility, or infertility. I found that prenatal exposure to the phthalate mixture significantly increased uterine weight and decreased anogenital distance at early ages, disrupted estrous cyclicity at multiple time points, and induced cystic ovaries at an old age. These observed adverse effects are probably the reason for the observed reduced fertility and increased breeding complications in phthalate mixture treated mice compared to controls. Further, I tested the hypothesis that prenatal exposure to an environmentally relevant phthalate mixture induces transgenerational disruption on female reproduction in mice. Multigenerational effects occur when the effects of a chemical are observed in more than one generation (F1 and F2). Transgenerational effects occur when the effects of a chemical is transmitted to the generations that are not directly exposed to the chemical, such as the F3 generation. I found that prenatal exposure to the phthalate mixture induced multigenerational and transgenerational effects in female mice. Specifically, the phthalate mixture significantly increased body weight at different ages in F2 and F3 females, increased liver weights in F2 females, decreased anogenital distance in F2 and F3 females, increased uterine weight in F2 females, induced cystic ovaries in F2 females, and caused breeding complications in F2 and F3 females. Taken together, these data suggest that prenatal exposure to an environmentally relevant phthalate mixture disrupts many aspects of female reproduction in F2 and F3 female mice. Collectively, my doctoral dissertation data suggest that exposure to an environmentally relevant phthalate mixture directly acts on antral follicles to reduce the health and function of antral follicles, and exposure to this mixture prenatally causes fertility problems in the first and the subsequent generations of female mice

Thermal stability of high temperature Pb-free solder interconnect characterised by in-situ electron microscopy

The present investigation aimed to use in-situ heating experiment in a transmission electron microscope (TEM) to live characterize the thermal stability of a Cu/Ni-W-P interlayer/ZnAl solder interconnect. It demonstrated the TEM was able to detect live intermetallic compounds (IMCs) growth during heating. In addition, stress building up was evidenced by the progressive evolving of the dislocations at the interface between NiW-P interlayer and the ZnAl Solder. However, due to the μm to nm scale of specimens' dimensions required for electron microscopy, the sample preparation and data interpretation remains a challenge

Abusive Supervision, Leader-Member Exchange, and Creativity: A Multilevel Examination

Despite the growing attention on the topic of abusive supervision, how abusive supervision affects individual and team creativity have not yet been thoroughly investigated. Drawn from the perspective of leader-member exchange (LMX), the current study develops a multilevel model to describe the relationships between abusive supervision and creativity at both team and individual levels, with a focus on the roles played by team-level leader-member exchange (TLMX) and LMX differentiation (DLMX). Based on data collected from 319 team members and their team leaders in 71 teams, the results show that abusive supervision has a negative relationship with TLMX, a practice that is conducive to both team and individual creativity. At the team level, the negative relationship between abusive supervision and TLMX is lessened by a higher level of DLMX. In addition, the positive relationship between TLMX and team creativity is weakened by a higher level of DLMX. Theoretical and practical implications of the findings are discussed

Rotating BTZ-like black hole and central charges in Einstein-bumblebee gravity

We obtain an exact rotating BTZ-like black hole solution by solving the corresponding gravitational field equations in Einstein-bumblebee gravity theory. Result is presented for the purely radial Lorentz symmetry violating and can only exist with a linear functional potential of the bumblebee field. This black hole has two horizons and an ergosphere which are dependent on the bumblebee coupling constant $\ell$. We study the AdS/CFT correspondence of this black hole, find that the entropy product of its inner and outer horizons is universal. So the central charges of the dual CFT on the boundary can be obtained via the thermodynamic method, and they can reappear black hole mass and angular momentum in the bulk.Comment: 12 pages, no figure. arXiv admin note: text overlap with arXiv:2201.0668

dugMatting: Decomposed-Uncertainty-Guided Matting

Cutting out an object and estimating its opacity mask, known as image matting, is a key task in image and video editing. Due to the highly ill-posed issue, additional inputs, typically user-defined trimaps or scribbles, are usually needed to reduce the uncertainty. Although effective, it is either time consuming or only suitable for experienced users who know where to place the strokes. In this work, we propose a decomposed-uncertainty-guided matting (dugMatting) algorithm, which explores the explicitly decomposed uncertainties to efficiently and effectively improve the results. Basing on the characteristic of these uncertainties, the epistemic uncertainty is reduced in the process of guiding interaction (which introduces prior knowledge), while the aleatoric uncertainty is reduced in modeling data distribution (which introduces statistics for both data and possible noise). The proposed matting framework relieves the requirement for users to determine the interaction areas by using simple and efficient labeling. Extensively quantitative and qualitative results validate that the proposed method significantly improves the original matting algorithms in terms of both efficiency and efficacy

Formation and homogenisation of Sn-Cu interconnects by self-propagated exothermic reactive bonding

We produced SnCu interconnects by self-propagated exothermic reactions using AlNi NanoFoil at ambient conditions, through the instantaneous localised heat across the interfaces between Sn electroplated Cu substrates. This technique presents a great potential for electronics integration with minimal thermal effects to the components. However, the metastable phases resulted from the non-equilibrium interfacial reactions and solidification were inevitable under a highly transient regime due to a drastic heating/cooling (over 107 K/s). In this study, Finite Element Analysis was performed to predict the temperature profiles across bonding interfaces, which were subsequently correlated with the formation and homogenisation of the bonded structures during the bonding and post-bonding ageing process. It has been revealed that, for nano-sized metastable phases, their formation, morphologies and distribution were primarily attributed to the convective mass transportation, liquid-solid inter-diffusion, and directional non-equilibrium solidification of Sn in molten zone of the bonding interfaces. The non-equilibrium phases initially formed in the SnCu interconnects can be homogenised towards the equilibrium status by accelerated ageing. This was achieved through the coalescing and subsequent growth of the original nano-sized metastable phases, as a result of the solid-diffusion of Cu and Ag atoms at intergranular boundary regions of Sn grains, AlNi NanoFoil/Sn. and Cu/Sn interfaces

Calibrating Multimodal Learning

Multimodal machine learning has achieved remarkable progress in a wide range of scenarios. However, the reliability of multimodal learning remains largely unexplored. In this paper, through extensive empirical studies, we identify current multimodal classification methods suffer from unreliable predictive confidence that tend to rely on partial modalities when estimating confidence. Specifically, we find that the confidence estimated by current models could even increase when some modalities are corrupted. To address the issue, we introduce an intuitive principle for multimodal learning, i.e., the confidence should not increase when one modality is removed. Accordingly, we propose a novel regularization technique, i.e., Calibrating Multimodal Learning (CML) regularization, to calibrate the predictive confidence of previous methods. This technique could be flexibly equipped by existing models and improve the performance in terms of confidence calibration, classification accuracy, and model robustness