Improvement of In Vitro Fertilization (IVF) Technology through Microfluidics.

Despite advances in in vitro manipulation of pre-implantation embryos, there is still a lag in the quality of embryos produced in vitro leading to lower pregnancy rates compared to embryos produced in vivo. Reducing the incidence of high-order multiple pregnancies while maintaining the overall in vitro fertilization (IVF) success rate is a holy grail of human IVF and would be greatly assisted by the ability to produce and identify the highest quality embryos. A promising new technology, microfluidics, does exist and is becoming increasingly studied. A challenge of studying embryo on microfluidic device is that preimplantation mouse embryos are highly sensitive cells and their development is affected greatly by osmolality shifts as will occur in devices with thin poly(dimethylsiloxane) (PDMS) membranes even in typical humidified cell culture incubators. Here we characterized and resolved evaporation mediated osmolity shifts that constrained microfluidic cell culture in Poly(dimethylsiloxane) devices. Next, we developed a dynamic microfunnel embryo culture system would enhance outcomes by better mimicking the fluid mechanical stimulation and chemical agitation embryos experience in vivo from ciliary currents and oviductal contractions. Using a mouse embryo model, average cell counts for blastocysts after 96 hours of culture in dynamic microfunnel conditions increased 70% over that of conventional static cultures. Importantly, the dynamic microfunnel cultures significantly improved embryo implantation and ongoing pregnancy rates over static culture to a level that approached that of in utero-derived preimplantation embryos. Lastly, we reported a new computerized microfluidic real time embryo culture and assay device that can perform automated periodic analyses of embryo metabolism over 24 hrs. Biochemical methods for embryo analysis based on measurement of metabolic rates do exist, but are not practical for clinical use because of difficulties in manipulating precise amounts of sample and reagents at the sub-microliter scale. The convenient, non-vasive, reliable, and automated nature of these assays open the way for development of practical single embryo biochemical analysis systems. Collectively, these results confirm that microfluidic technology can be used to properly mimic a broad range of the embryo environments seen in physiology and to assess embryo viability for in vitro fertilization clinics.Ph.D.Biomedical EngineeringUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/61666/1/yunsheo_1.pd

Quantitative local probing of polarization with application on HfO 2 ‐based thin films

Owing to their switchable spontaneous polarization, ferroelectric materials have been applied in various fields, such as information technologies, actuators, and sensors. In the last decade, as the characteristic sizes of both devices and materials have decreased significantly below the nanoscale, the development of appropriate characterization tools became essential. Recently, a technique based on conductive atomic force microscopy (AFM), called AFM‐positive‐up‐negative‐down (PUND), is employed for the direct measurement of ferroelectric polarization under the AFM tip. However, the main limitation of AFM‐PUND is the low frequency (i.e., on the order of a few hertz) that is used to initiate ferroelectric hysteresis. A significantly higher frequency is required to increase the signal‐to‐noise ratio and the measurement efficiency. In this study, a novel method based on high‐frequency AFM‐PUND using continuous waveform and simultaneous signal acquisition of the switching current is presented, in which polarization–voltage hysteresis loops are obtained on a high‐polarization BiFeO3 nanocapacitor at frequencies up to 100 kHz. The proposed method is comprehensively evaluated by measuring nanoscale polarization values of the emerging ferroelectric Hf0.5Zr0.5O2 under the AFM tip

Redox-driven control of magnetism and structure of polycrystalline PrBaCo2O5+δ

Controlling oxygen contents (0.25 ≤  δ  ≤ 0.83) and its associated structural and magnetic properties in polycrystalline PrBaCo _2 O _5+ _δ are presented. To control oxygen contents, heat treatments were performed using tube furnace in controlled gas environment. Through temperature dependent reductive annealing, oxygen vacancies are formed in PBCO, and changes of associated properties such as lattice expansion and stabilization of antiferromagnetism are observed. When we performed oxidative annealing, oxygens are intercalated into PBCO. This results in stabilization of ferromagnetism. At last, we checked reversibility through consecutive redox reactions. The structural and magnetic phase transitions occur nearly reversibly. Thus, we could control oxygen contents and associated structural and magnetic properties reversibly through conventional gas reaction

The Multivalent Polyampholyte Domain of Nst1, a P-Body-Associated <i>Saccharomyces cerevisiae</i> Protein, Provides a Platform for Interacting with P-Body Components

The condensation of nuclear promyelocytic leukemia bodies, cytoplasmic P-granules, P-bodies (PBs), and stress granules is reversible and dynamic via liquid–liquid phase separation. Although each condensate comprises hundreds of proteins with promiscuous interactions, a few key scaffold proteins are required. Essential scaffold domain sequence elements, such as poly-Q, low-complexity regions, oligomerizing domains, and RNA-binding domains, have been evaluated to understand their roles in biomolecular condensation processes. However, the underlying mechanisms remain unclear. We analyzed Nst1, a PB-associated protein that can intrinsically induce PB component condensations when overexpressed. Various Nst1 domain deletion mutants with unique sequence distributions, including intrinsically disordered regions (IDRs) and aggregation-prone regions, were constructed based on structural predictions. The overexpression of Nst1 deletion mutants lacking the aggregation-prone domain (APD) significantly inhibited self-condensation, implicating APD as an oligomerizing domain promoting self-condensation. Remarkably, cells overexpressing the Nst1 deletion mutant of the polyampholyte domain (PD) in the IDR region (Nst1∆PD) rarely accumulate endogenous enhanced green fluorescent protein (EGFP)-tagged Dcp2. However, Nst1∆PD formed self-condensates, suggesting that Nst1 requires PD to interact with Dcp2, regardless of its self-condensation. In Nst1∆PD-overexpressing cells treated with cycloheximide (CHX), Dcp2, Xrn1, Dhh1, and Edc3 had significantly diminished condensation compared to those in CHX-treated Nst1-overexpressing cells. These observations suggest that the PD of the IDR in Nst1 functions as a hub domain interacting with other PB components

Formation of buried superconducting Mo2N by nitrogen-ion-implantation

Nitrogen ion implantation is a useful technique to put nitrogen ions into lattices. In this work, nitrogen ion implantation into epitaxial Mo films is performed to create a buried superconducting gamma-Mo2N. Atomically flat epitaxial (110) Mo films are grown on (0001) Al2O3. By impinging nitrogen ions, where the beam energy is fixed to 20 keV, we observe (111) gamma-Mo2N diffraction and the formation of a gamma-Mo2N layer from X-ray reflectivity. Magnetization and transport measurements clearly support a superconducting layer in the implanted film. Our strategy shows that formation of a buried superconducting layer can be achieved through ion implantation and self-annealing

Flexoelectric healing of intrinsically more conductive nanochannels in NdNiO3 thin films

Rare-earth nickelates have received great attention owing to the extreme sensitivity of their metal-insulator transition (MIT) and particularly the local defect state under external perturbation. Accordingly, it is critical to effectively control their local defect state to tailor the MIT. However, although macroscopic MIT behavior has been extensively studied, the relationship between the local defect state related to polar discontinuity and MIT has been rarely investigated. Herein, we demonstrate the presence of intrinsic conductive nanochannels due to the Ni deficiency induced by the polar discontinuity and the flexoelectric healing of such nanochannels in NdNiO3 thin films using atomic force microscopy (AFM). The results indicate that the intrinsic conductive nanochannels are likely related to the Ni vacancy. Intriguingly, these conductive nanochannels are effectively removed by the application of mechanical force with the AFM tip, i.e., flexoelectric healing. Our findings suggest that mechanical stimuli can be one of the effective ways for modulating the intrinsic defect state and the corresponding properties at the nanoscale

Dermatobacter hominis gen. nov., sp. nov., a new member of the family Iamiaceae, revealed the potential utilisation of skin-derived metabolites

[EN]A non-motile, novel actinobacterial strain, Kera-3T, which is a gram-positive, aerobic, rod-shaped bacterium, was isolated from human keratinocytes on 1/10 diluted R2A agar. Whole-cell hydrolysis of amino acids revealed the presence of meso-DAP, alanine, and glutamic acid. The predominant menaquinone was MK-9 (H8), whereas the primary fatty acids were C16:0 and C18:1 ω9c. The major phospholipids included diphosphatidylglycerol and aminophospholipids, along with an unidentified phosphoglycolipid and an aminophosphoglycolipid. The G+C content of the genomic DNA was 73.2%, based on the complete genome sequence. Phylogenetic analyses of the 16S rRNA gene sequence and phylogenomic analysis of 91 core genes showed that strain Kera-3T formed a new lineage in the family Iamiaceae, with the closest neighbour Rhabdothermincola sediminis SYSU G02662T having 91.19% 16S rRNA gene sequence identity. A comparative genomic study of the predicted general metabolism and carbohydrate-active enzymes supported the phylogenetic and phylogenomic data. Based on the analysis of physiological, biochemical, and genomic characteristics, strain Kera-3T can be distinguished from known genera in the family Iamiaceae and represents a novel genus and species. Therefore, the name Dermatobacter hominis gen. nov., sp. nov. was proposed, with the type strain Kera-3T (= KACC 22415T = LMG 32493T)

Structural and Functional Characterizations of Cancer Targeting Nanoparticles Based on Hepatitis B Virus Capsid

Cancer targeting nanoparticles have been extensively studied, but stable and applicable agents have yet to be developed. Here, we report stable nanoparticles based on hepatitis B core antigen (HBcAg) for cancer therapy. HBcAg monomers assemble into spherical capsids of 180 or 240 subunits. HBcAg was engineered to present an affibody for binding to human epidermal growth factor receptor 1 (EGFR) and to present histidine and tyrosine tags for binding to gold ions. The HBcAg engineered to present affibody and tags (HAF) bound specifically to EGFR and exterminated the EGFR-overexpressing adenocarcinomas under alternating magnetic field (AMF) after binding with gold ions. Using cryogenic electron microscopy (cryo-EM), we obtained the molecular structures of recombinant HAF and found that the overall structure of HAF was the same as that of HBcAg, except with the affibody on the spike. Therefore, HAF is viable for cancer therapy with the advantage of maintaining a stable capsid form. If the affibody in HAF is replaced with a specific sequence to bind to another targetable disease protein, the nanoparticles can be used for drug development over a wide spectrum

Highly enhanced ferroelectricity in HfO2-based ferroelectric thin film by light ion bombardment

Continuous advancement in nonvolatile and morphotropic beyond-Moore electronic devices requires integration of ferroelectric and semiconductor materials. The emergence of hafnium oxide (HfO2)-based ferroelectrics that are compatible with atomic-layer deposition has opened interesting and promising avenues of research. However, the origins of ferroelectricity and pathways to controlling it in HfO2 are still mysterious. We demonstrate that local helium (He) implantation can activate ferroelectricity in these materials. The possible competing mechanisms, including He ion-induced molar volume changes, vacancy redistribution, vacancy generation, and activation of vacancy mobility, are analyzed. These findings both reveal the origins of ferroelectricity in this system and open pathways for nanoengineered binary ferroelectrics