Recent technological updates and clinical applications of induced pluripotent stem cells

Induced pluripotent stem cells (iPSCs) were first described in 2006 and have since emerged as a promising cell source for clinical applications. The rapid progression in iPSC technology is still ongoing and directed toward increasing the efficacy of iPSC production and reducing the immunogenic and tumorigenic potential of these cells. Enormous efforts have been made to apply iPSC-based technology in the clinic, for drug screening approaches and cell replacement therapy. Moreover, disease modeling using patient-specific iPSCs continues to expand our knowledge regarding the pathophysiology and prospective treatment of rare disorders. Furthermore, autologous stem cell therapy with patient-specific iPSCs shows great propensity for the minimization of immune reactions and the provision of a limitless supply of cells for transplantation. In this review, we discuss the recent updates in iPSC technology and the use of iPSCs in disease modeling and regenerative medicine

Generation of functional cardiomyocytes from the synoviocytes of patients with rheumatoid arthritis via induced pluripotent stem cells

Cardiovascular disease is a leading cause of morbidity in rheumatoid arthritis (RA) patients. This study aimed to generate and characterise cardiomyocytes from induced pluripotent stem cells (iPSCs) of RA patients. Fibroblast-like synoviocytes (FLSs) from patients with RA and osteoarthritis (OA) were successfully reprogrammed into RA-iPSCs and OA-iPSCs, respectively. The pluripotency of iPSCs was confirmed by quantitative reverse transcription-polymerase chain reaction and immunofluorescence staining. Established iPSCs were differentiated into cardiomyocytes using a small molecule-based monolayer differentiation protocol. Within 12 days of cardiac differentiation from patient-specific and control-iPSCs, spontaneously beating cardiomyocytes (iPSC-CMs) were observed. All iPSC-CMs exhibited a reliable sarcomeric structure stained with antibodies against cardiac markers and similar expression profiles of cardiac-specific genes. Intracellular calcium signalling was recorded to compare calcium-handling properties among cardiomyocytes differentiated from the three groups of iPSCs. RA-iPSC-CMs had a lower amplitude and a shorter duration of calcium transients than the control groups. Peak tangential stress and the maximum contractile rate were also decreased in RA-iPSC-CMs, suggesting that contractility was reduced. This study demonstrates the successful generation of functional cardiomyocytes from pathogenic synovial cells in RA patients through iPSC reprogramming. Research using RA-iPSC-CMs might provide an opportunity to investigate the pathophysiology of cardiac involvement in RA

Percolative phase separation induced by nonuniformly distributed excess oxygens

The zero-field $^{139}$La and $^{55}$Mn nuclear magnetic resonances were studied in $\rm La_{0.8}Ca_{0.2}MnO_{3+\delta}$ with different oxygen stoichiometry $\delta$. The signal intensity, peak frequency and line broadening of the $^{139}$La NMR spectrum show that excess oxygens have a tendency to concentrate and establish local ferromagnetic ordering around themselves. These connect the previously existed ferromagnetic clusters embedded in the antiferromagnetic host, resulting in percolative conduction paths. This phase separation is not a charge segregation type, but a electroneutral type. The magnetoresistance peak at the temperature where percolative paths start to form provides a direct evidence that phase separation is one source of colossal magnetoresistance effect.Comment: 4 pages, 5 figure

Gravitational-wave Detection With Matter-wave Interferometers Based On Standing Light Waves

We study the possibility of detecting gravitational-waves with matter-wave interferometers, where atom beams are split, deflected and recombined totally by standing light waves. Our calculation shows that the phase shift is dominated by terms proportional to the time derivative of the gravitational wave amplitude. Taking into account future improvements on current technologies, it is promising to build a matter-wave interferometer detector with desired sensitivity.Comment: 7 pages, 3 figures. To be published in General Relativity and Gravitatio

Temperature Dependence of Low-Lying Electronic Excitations of LaMnO_3

We report on the optical properties of undoped single crystal LaMnO_3, the parent compound of the colossal magneto-resistive manganites. Near-Normal incidence reflectance measurements are reported in the frequency range of 20-50,000 cm-1 and in the temperature range 10-300 K. The optical conductivity, s_1(w), is derived by performing a Kramers-Kronig analysis of the reflectance data. The far-infrared spectrum of s_1(w) displays the infrared active optical phonons. We observe a shift of several of the phonon to high frequencies as the temperature is lowered through the Neel temperature of the sample (T_N = 137 K). The high-frequency s_1(w) is characterized by the onset of absorption near 1.5 eV. This energy has been identified as the threshold for optical transitions across the Jahn-Teller split e_g levels. The spectral weight of this feature increases in the low-temperature state. This implies a transfer of spectral weight from the UV to the visible associated with the paramagnetic to antiferromagnetic state. We discuss the results in terms of the double exchange processes that affect the optical processes in this magnetic material.Comment: 7 pages, 5 figure

Green and efficient production of octyl hydroxyphenylpropionate using an ultrasound-assisted packed-bed bioreactor

A solvent-free system to produce octyl hydroxyphenylpropionate (OHPP) from p-hydroxyphenylpropionic acid (HPPA) and octanol using immobilized lipase (Novozym(A (R)) 435) as a catalyst in an ultrasound-assisted packed-bed bioreactor was investigated. Response-surface methodology (RSM) and a three-level-three-factor Box-Behnken design were employed to evaluate the effects of reaction temperature (x (1)), flow rate (x (2)) and ultrasonic power (x (3)) on the percentage of molar production of OHPP. The results indicate that the reaction temperature and flow rate were the most important variables in optimizing the production of OHPP. Based on a ridge max analysis, the optimum conditions for OHPP synthesis were predicted to consist of a reaction temperature of 65A degrees C, a flow rate of 0.05 ml/min and an ultrasonic power of 1.74 W/cm(2) with a yield of 99.25%. A reaction was performed under these optimal conditions, and a yield of 99.33 +/- A 0.1% was obtained

Graft immaturity and safety concerns in transplanted human kidney organoids

For chronic kidney disease, regeneration of lost nephrons with human kidney organoids derived from induced pluripotent stem (iPS) cells is proposed to be an attractive potential therapeutic option. It remains unclear, however, whether organoids transplanted into kidneys in vivo would be safe or functional. Here, we purified kidney organoids and transplanted them beneath the kidney capsules of immunodeficient mice to test their safety and maturity. Kidney organoid grafts survived for months after transplantation and became vascularized from host mouse endothelial cells. Nephron-like structures in grafts appeared more mature than kidney organoids in vitro, but remained immature compared with the neighboring mouse kidney tissue. Ultrastructural analysis revealed filtration barrier-like structures, capillary lumens, and tubules with brush border in the transplanted kidney organoids, which were more mature than those of the kidney organoids in vitro but not as organized as adult mammalian kidneys. Immaturity was a common feature of three separate differentiation protocols by immunofluorescence analysis and single cell RNA sequencing. Stroma of transplanted kidney organoid grafts were filled with vimentin-positive mesenchymal cells, and chondrogenesis, cystogenesis, and stromal expansion were observed in the long term. Transcription profiles showed that long-term maintenance after kidney organoid transplantation induced transcriptomic reprogramming with prominent suppression of cell-cycle-related genes and upregulation of extracellular matrix organization. Our data suggest that kidney organoids derived from iPS cells may be transplantable but strategies to improve nephron differentiation and purity are required before they can be applied in humans as a therapeutic option.11Ysciescopuskc

Correlated noise in a logistic growth model

The logistic differential equation is used to analyze cancer cell population, in the presence of a correlated Gaussian white noise. We study the steady state properties of tumor cell growth and discuss the effects of the correlated noise. It is found that the degree of correlation of the noise can cause tumor cell extinction.Comment: 3 pages, 4 figure

Search for sterile neutrino oscillation using RENO and NEOS data

We present a reactor model independent search for sterile neutrino oscillation using 2\,509\,days of RENO near detector data and 180 days of NEOS data. The reactor related systematic uncertainties are significantly suppressed as both detectors are located at the same reactor complex of Hanbit Nuclear Power Plant. The search is performed by electron antineutrino\,($\overline{\nu}_e$) disappearance between six reactors and two detectors with baselines of 294\,m\,(RENO) and 24\,m\,(NEOS). A spectral comparison of the NEOS prompt-energy spectrum with a no-oscillation prediction from the RENO measurement can explore reactor $\overline{\nu}_e$ oscillations to sterile neutrino. Based on the comparison, we obtain a 95\% C.L. excluded region of $0.1<|\Delta m_{41}^2|<7$\,eV$^2$. We also obtain a 68\% C.L. allowed region with the best fit of $|\Delta m_{41}^2|=2.41\,\pm\,0.03\,$\,eV$^2$ and $\sin^2 2\theta_{14}$=0.08$\,\pm\,$0.03 with a p-value of 8.2\%. Comparisons of obtained reactor antineutrino spectra at reactor sources are made among RENO, NEOS, and Daya Bay to find a possible spectral variation.Comment: 6 pages, 5 figures: This manuscript has been significantly revised by the joint reanalysis by RENO and NEOS Collaborations. (In the previous edition, the RENO collaboration used publicly available NEOS data to evaluate the expected neutrino spectrum at NEOS.

Formation of Nanopits in Si Capping Layers on SiGe Quantum Dots

In-situ annealing at a high temperature of 640°C was performed for a low temperature grown Si capping layer, which was grown at 300°C on SiGe self-assembled quantum dots with a thickness of 50 nm. Square nanopits, with a depth of about 8 nm and boundaries along 〈110〉, are formed in the Si capping layer after annealing. Cross-sectional transmission electron microscopy observation shows that each nanopit is located right over one dot with one to one correspondence. The detailed migration of Si atoms for the nanopit formation is revealed by in-situ annealing at a low temperature of 540°C. The final well-defined profiles of the nanopits indicate that both strain energy and surface energy play roles during the nanopit formation, and the nanopits are stable at 640°C. A subsequent growth of Ge on the nanopit-patterned surface results in the formation of SiGe quantum dot molecules around the nanopits