Effect of oral administration of pioglitazone on follicular dynamics in Holstein dairy cows

This study investigated the effects of oral administration of pioglitazone (PGT), a specific and synthetic ligand of peroxisome proliferator-activated receptors gamma (PPARγ), on follicular dynamics and corpus luteum (CL) functionality in dairy cows. Cows exhibiting strong signs of estrus after 2 injections of PGF2α (given14 d apart) at d 30 postpartum (n = 28) were allotted to four groups (n = 7 cows/treatment) and orally received 6 mg PGT/kg body weight/day according to the following protocol: no PGT (control); PGT for 14 d from 7 d before expected estrus (10 d after 1st injection of PGF2α) to 7 d after observed estrus (PGT14); PGT for 21 d after observed estrus (PGT21); and PGT for 28 d, 7 d before expected estrus to 21 d after observed estrus (PGT28). During the first follicular wave, number of follicles (total and small) increased in PGT14 and PGT28 cows compared to the control group (P < 0.05). During the ovulatory wave, number of total and small follicles increased in PGT28 (P < 0.05) and PGT21 (P < 0.10) compared with PGT14 and control cows. Size of the largest follicle at first wave was greater in PGT28 (P < 0.05), PGT14 (P < 0.05) and PGT21 (P < 0.10) compared to the control cows. Maximal size of the ovulatory follicle was greater in PGT28 (P < 0.05) and PGT21 (P < 0.10) groups compared to the control group. Growth rate of the largest follicle at first wave was higher (P < 0.05) in PGT-treated cows, while growth rate of the ovulatory wave was higher in PGT28 and PGT21 groups, leading to shorter days from luteolysis to ovulation. Pioglitazone administration did not affect CL size, but increased progesterone (P4) concentration. The PGT14 and PGT28 cows had higher maximal plasma P4 concentration and shorter intervals to reach maximal plasma P4 compared to the control group. In conclusion, oral administration of PGT had some positive effects on follicular development and circulating P4 levels which may be conducive to better reproductive performance

Fuzz, Penetration, and AI Testing for SoC Security Verification: Challenges and Solutions

The ever-increasing usage and application of system-on-chips (SoCs) has resulted in the tremendous modernization of these architectures. For a modern SoC design, with the inclusion of numerous complex and heterogeneous intellectual properties (IPs), and its privacy-preserving declaration, there exists a wide variety of highly sensitive assets. These assets must be protected from any unauthorized access and against a diverse set of attacks. Attacks for obtaining such assets could be accomplished through different sources, including malicious IPs, malicious or vulnerable firmware/software, unreliable and insecure interconnection and communication protocol, and side-channel vulnerabilities through power/performance profiles. Any unauthorized access to such highly sensitive assets may result in either a breach of company secrets for original equipment manufactures (OEM) or identity theft for the end-user. Unlike the enormous advances in functional testing and verification of the SoC architecture, security verification is still on the rise, and little endeavor has been carried out by academia and industry. Unfortunately, there exists a huge gap between the modernization of the SoC architectures and their security verification approaches. With the lack of automated SoC security verification in modern electronic design automation (EDA) tools, we provide a comprehensive overview of the requirements that must be realized as the fundamentals of the SoC security verification process in this paper. By reviewing these requirements, including the creation of a unified language for SoC security verification, the definition of security policies, formulation of the security verification, etc., we put forward a realization of the utilization of self-refinement techniques, such as fuzz, penetration, and AI testing, for security verification purposes. We evaluate all the challenges and resolution possibilities, and we provide the potential approaches for the realization of SoC security verification via these self-refinement techniques

Bio-nanotechnology application in wastewater treatment

The nanoparticles have received high interest in the field of medicine and water purification, however, the nanomaterials produced by chemical and physical methods are considered hazardous, expensive, and leave behind harmful substances to the environment. This chapter aimed to focus on green-synthesized nanoparticles and their medical applications. Moreover, the chapter highlighted the applicability of the metallic nanoparticles (MNPs) in the inactivation of microbial cells due to their high surface and small particle size. Modifying nanomaterials produced by green-methods is safe, inexpensive, and easy. Therefore, the control and modification of nanoparticles and their properties were also discussed

Clinical study protocol for a low-interventional study in intermediate age-related macular degeneration developing novel clinical endpoints for interventional clinical trials with a regulatory and patient access intention-MACUSTAR.

BACKGROUND: There is an unmet need for treatment options in intermediate age-related macular degeneration (iAMD). However, for any new interventions to be tested in clinical trials, novel currently unavailable clinical endpoints need to be developed. Thus, the MACUSTAR study aims to develop and evaluate functional, structural, and patient-reported candidate endpoints for use in future iAMD trials. METHODS: The protocol describes a low-interventional clinical multicenter study employing a novel two-part design. The cross-sectional part (total duration, 1 month) and the longitudinal part (total duration, 36 months) include participants with iAMD and control groups with early/late/no AMD. The cross-sectional part's primary objective is a technical evaluation of functional, structural, and patient-reported candidate outcomes. The longitudinal part's primary objective is to assess the prognostic power of changes in functional, structural, and patient-reported outcomes for progression from iAMD to late AMD. All data will be used to support a biomarker qualification procedure by regulatory authorities. DISCUSSION: The MACUSTAR study characterizes and evaluates much needed novel functional, structural, and patient-reported endpoints for future clinical trials in iAMD and will improve our understanding of the natural history and prognostic markers of this condition. TRIAL REGISTRATION: ClinicalTrials.gov NCT03349801 . Registered on 22 November 2017

Autoimmune and autoinflammatory mechanisms in uveitis

The eye, as currently viewed, is neither immunologically ignorant nor sequestered from the systemic environment. The eye utilises distinct immunoregulatory mechanisms to preserve tissue and cellular function in the face of immune-mediated insult; clinically, inflammation following such an insult is termed uveitis. The intra-ocular inflammation in uveitis may be clinically obvious as a result of infection (e.g. toxoplasma, herpes), but in the main infection, if any, remains covert. We now recognise that healthy tissues including the retina have regulatory mechanisms imparted by control of myeloid cells through receptors (e.g. CD200R) and soluble inhibitory factors (e.g. alpha-MSH), regulation of the blood retinal barrier, and active immune surveillance. Once homoeostasis has been disrupted and inflammation ensues, the mechanisms to regulate inflammation, including T cell apoptosis, generation of Treg cells, and myeloid cell suppression in situ, are less successful. Why inflammation becomes persistent remains unknown, but extrapolating from animal models, possibilities include differential trafficking of T cells from the retina, residency of CD8(+) T cells, and alterations of myeloid cell phenotype and function. Translating lessons learned from animal models to humans has been helped by system biology approaches and informatics, which suggest that diseased animals and people share similar changes in T cell phenotypes and monocyte function to date. Together the data infer a possible cryptic infectious drive in uveitis that unlocks and drives persistent autoimmune responses, or promotes further innate immune responses. Thus there may be many mechanisms in common with those observed in autoinflammatory disorders

Doyne lecture 2016:intraocular health and the many faces of inflammation

Dogma for reasons of immune privilege including sequestration (sic) of ocular antigen, lack of lymphatic and immune competent cells in the vital tissues of the eye has long evaporated. Maintaining tissue and cellular health to preserve vision requires active immune responses to prevent damage and respond to danger. A priori the eye must contain immune competent cells, undergo immune surveillance to ensure homoeostasis as well as an ability to promote inflammation. By interrogating immune responses in non-infectious uveitis and compare with age-related macular degeneration (AMD), new concepts of intraocular immune health emerge. The role of macrophage polarisation in the two disorders is a tractable start. TNF-alpha regulation of macrophage responses in uveitis has a pivotal role, supported via experimental evidence and validated by recent trial data. Contrast this with the slow, insidious degeneration in atrophic AMD or in neovasular AMD, with the compelling genetic association with innate immunity and complement, highlights an ability to attenuate pathogenic immune responses and despite known inflammasome activation. Yolk sac-derived microglia maintains tissue immune health. The result of immune cell activation is environmentally dependent, for example, on retinal cell bioenergetics status, autophagy and oxidative stress, and alterations that skew interaction between macrophages and retinal pigment epithelium (RPE). For example, dead RPE eliciting macrophage VEGF secretion but exogenous IL-4 liberates an anti-angiogenic macrophage sFLT-1 response. Impaired autophagy or oxidative stress drives inflammasome activation, increases cytotoxicity, and accentuation of neovascular responses, yet exogenous inflammasome-derived cytokines, such as IL-18 and IL-33, attenuate responses

Investigation of the effect of temper rolling on the texture evolution and mechanical behavior of IF steels using multiscale simulation

The main objective of this study is to simulate texture and deformation during the temper-rolling process. To this end, a rate-independent crystal plasticity model, based on the self-consistent scale-transition scheme, is adopted to predict texture evolution and deformation heterogeneity during temper-rolling process. For computational efficiency, a decoupled analysis is considered between the polycrystalline plasticity model and the finite element analysis for the temper rolling. The elasto-plastic finite element analysis is first carried out to determine the history of velocity gradient during the numerical simulation of temper rolling. The thus calculated velocity gradient history is subsequently applied to the polycrystalline plasticity model. By following some appropriately selected strain paths (i.e., streamlines) along the rolling process, one can predict the texture evolution of the material at the half thickness of the sheet metal as well as other parameters related to its microstructure. The numerical results obtained by the proposed strategy are compared with experimental data in the case of IF steels.French program “Investment in the future” operated by the National Research Agency (ANR)-11-LABX-0008-01, LabEx DAMAS (LST)