Area-selective atomic layer deposition on 2D monolayer lateral superlattices.

The advanced patterning process is the basis of integration technology to realize the development of next-generation high-speed, low-power consumption devices. Recently, area-selective atomic layer deposition (AS-ALD), which allows the direct deposition of target materials on the desired area using a deposition barrier, has emerged as an alternative patterning process. However, the AS-ALD process remains challenging to use for the improvement of patterning resolution and selectivity. In this study, we report a superlattice-based AS-ALD (SAS-ALD) process using a two-dimensional (2D) MoS2-MoSe2 lateral superlattice as a pre-defining template. We achieved a minimum half pitch size of a sub-10 nm scale for the resulting AS-ALD on the 2D superlattice template by controlling the duration time of chemical vapor deposition (CVD) precursors. SAS-ALD introduces a mechanism that enables selectivity through the adsorption and diffusion processes of ALD precursors, distinctly different from conventional AS-ALD method. This technique facilitates selective deposition even on small pattern sizes and is compatible with the use of highly reactive precursors like trimethyl aluminum. Moreover, it allows for the selective deposition of a variety of materials, including Al2O3, HfO2, Ru, Te, and Sb2Se3.

Gut taste receptor type 1 member 3 is an intrinsic regulator of Western diet-induced intestinal inflammation.

BACKGROUND: Long-term intake of a Western diet (WD), characterized by a high-fat content and sugary drinks, is hypothesized to contribute to the development of inflammatory bowel disease (IBD). Despite the identified clinical association, the molecular mechanisms by which dietary changes contribute to IBD development remain unknown. Therefore, we examined the influence of long-term intake of a WD on intestinal inflammation and the mechanisms by which WD intake affects IBD development. METHODS: Mice fed normal diet or WD for 10 weeks, and bowel inflammation was evaluated through pathohistological and infiltrated inflammatory cell assessments. To understand the role of intestinal taste receptor type 1 member 3 (TAS1R3) in WD-induced intestinal inflammation, cultured enteroendocrine cells harboring TAS1R3, subjected to RNA interference or antagonist treatment, and Tas1r3-deficient mice were used. RNA-sequencing, flow cytometry, 16S metagenomic sequencing, and bioinformatics analyses were performed to examine the involved mechanisms. To demonstrate their clinical relevance, intestinal biopsies from patients with IBD and mice with dextran sulfate sodium-induced colitis were analyzed. RESULTS: Our study revealed for the first time that intestinal TAS1R3 is a critical mediator of WD-induced intestinal inflammation. WD-fed mice showed marked TAS1R3 overexpression with hallmarks of serious bowel inflammation. Conversely, mice lacking TAS1R3 failed to exhibit inflammatory responses to WD. Mechanistically, intestinal transcriptome analysis revealed that Tas1r3 deficiency suppressed mTOR signaling, significantly increasing the expression of PPARγ (a major mucosal defense enhancer) and upregulating the expression of PPARγ target-gene (tight junction protein and antimicrobial peptide). The gut microbiota of Tas1r3-deficient mice showed expansion of butyrate-producing Clostridia. Moreover, an increased expression of host PPARγ-signaling pathway proteins was positively correlated with butyrate-producing microbes, suggesting that intestinal TAS1R3 regulates the relationship between host metabolism and gut microflora in response to dietary factors. In cultured intestinal cells, regulation of the TAS1R3-mTOR-PPARγ axis was critical for triggering an inflammatory response via proinflammatory cytokine production and secretion. Abnormal regulation of the axis was observed in patients with IBD. CONCLUSIONS: Our findings suggest that the TAS1R3-mTOR-PPARγ axis in the gut links Western diet consumption with intestinal inflammation and is a potential therapeutic target for IBD.

Amidoxime-Containing Ti Precursors for Atomic Layer Deposition of TiN Thin Films with Suppressed Columnar Microstructure.

This paper reports the synthesis of three novel titanium complexes containing amidoxime ligands as potential precursors for titanium nitride (TiN) thin films fabricated using atomic layer deposition (ALD). A series of ligands, viz., N'-methoxy-N-methylacetimidamide (mnnoH), N'-ethoxy-N-methylacetimidamide (ennoH), and N'-methoxy-N-methylbenzimidamide (pnnoH), were successfully synthesized and used to produce Ti(mnno)(NMe2)3 (4), Ti(enno)(NMe2)3 (5), and Ti(pnno)(NMe2)3 (6). Thermogravimetric analysis curves of complexes 4-6 revealed a single-step weight loss up to 200 °C. Pyrolysis occurred beyond 200 °C. Among the three new complexes, 5 was liquid at room temperature. Therefore, TiN was synthesized by ALD using Ti(enno)(NMe2)3 (5) as a novel precursor. A TiN thin film was deposited from the Ti(enno)(NMe2)3 (5) precursor and NH3 plasma, and self-limiting growth was achieved by varying the injection/purge duration. TiN thin film growths were observed with a growth per cycle (GPC) of 0.05-0.13 nm·cy-1 at deposition temperatures between 150 and 300 °C, while the measured resistivity was as low as 420 µΩ·cm. The high reactivity of the precursor promotes nucleation, resulting in TiN thin films with smooth, good step coverage and preferentially orientated microstructure.

Hyperradiance by a stream of phase-correlated atomic dipole pairs traversing a high-Q cavity.

Hyperradiance in which radiation rate exceeds that of superradiance has been theoretically investigated in various coherently-coupled emitter-field systems. In most cases, either proposed setups were experimentally challenging or the mean photon number in a cavity was limited. In this paper, with numerical simulations and analytic calculations, we demonstrate that significant hyperradiance with a large mean photon number can occur in a microlaser system, where pairs of two-level atoms prepared in quantum superposition states traverse a high-Q cavity in the presence of a pump field intersecting the cavity mode. Hyperradiance is induced when the intracavity-pump Rabi frequency is out of phase with respect to the atom-cavity coupling so that the reduction of atomic polarization by the atom-cavity coupling is compensated by the pump Rabi frequency in the steady state to maximize atomic photoemission.

Three-Dimensional Reproducibility of the Soft Tissue Landmarks Taken by Structured-Light Facial Scanner in Accordance with the Head Position Change.

The aim of this study was to evaluate the three-dimensional reproducibility of the structured-light facial scanner according to the head position change. A mannequin head was used and angle of the mannequin's axis-orbital plane to the true horizontal plane was adjusted to +10, +5, 0, -5, and -10°. Facial scanning was conducted 30 times, respectively, and 150 3D images were obtained. Reoriented landmarks of each group were compared and analyzed. Reproducibility decreased as the distance from the facial center increased. Additionally, the landmarks below showed lower reproducibility and higher dispersion than landmarks above. These differences occurred mainly in the anteroposterior direction as opposed to other directions. Positive inclination of the head position showed superior reproducibility compared to a negative inclination. This study showed that reproducibility of a structured-light scanner could be varied depending on the head position. Inaccuracies of landmarks in the anteroposterior direction are greater than in other directions. This means that evaluations of the profile using a structured-light scanner should be made carefully. Therefore, the proper head position should be set to ensure the accuracy of the image.

Coherent single-atom superradiance.

Superradiance is a quantum phenomenon emerging in macroscopic systems whereby correlated single atoms cooperatively emit photons. Demonstration of controlled collective atom-field interactions has resulted from the ability to directly imprint correlations with an atomic ensemble. Here we report cavity-mediated coherent single-atom superradiance: Single atoms with predefined correlation traverse a high-quality factor cavity one by one, emitting photons cooperatively with the N atoms that have already gone through the cavity (N represents the number of atoms). Enhanced collective photoemission of N-squared dependence was observed even when the intracavity atom number was less than unity. The correlation among single atoms was achieved by nanometer-precision position control and phase-aligned state manipulation of atoms by using a nanohole-array aperture. Our results demonstrate a platform for phase-controlled atom-field interactions.

Ultrafast photocarrier dynamics related to defect states of Si1-xGex nanowires measured by optical pump-THz probe spectroscopy.

Slightly tapered Si1-xGex nanowires (NWs) (x = 0.29-0.84) were synthesized via a vapor-liquid-solid procedure using Au as a catalyst. We measured the optically excited carrier dynamics of Si1-xGex NWs as a function of Ge content using optical pump-THz probe spectroscopy. The measured -ΔT/T0 signals of Si1-xGex NWs were converted into conductivity in the THz region. We developed a fitting formula to apply to indirect semiconductors such as Si1-xGex, which explains the temporal population of photo-excited carriers in the band structure and the relationship between the trapping time and the defect states on an ultrafast time scale. From the fitting results, we extracted intra- and inter-valley transition times and trapping times of electrons and holes of Si1-xGex NWs as a function of Ge content. On the basis of theoretical reports, we suggest a physical model to interpret the trapping times related to the species of interface defect states located at the oxide/NW: substoichiometric oxide states of Si(Ge)0+,1+,2+, but not Si(Ge)3+, could function as defect states capturing photo-excited electrons or holes and could determine the different trapping times of electrons and holes depending on negatively or neutrally charged states.

Generation and Stability of Bulk Nanobubbles.

Recently, extremely small bubbles, referred to as nanobubbles, have drawn increased attention due to their novel properties and great potential for various applications. In this study, a novel method for the generation of bulk nanobubbles (BNBs) was introduced, and stability of fabricated BNBs was investigated. BNBs were created from CO2 gas with a mixing method; the chemical identity and phase state of these bubbles can be determined via infrared spectroscopy. The presence of BNBs was observed with a nanoparticle tracking analysis (NTA). The ATR-FTIR spectra of BNBs indicate that the BNBs were filled with CO2 gas. Furthermore, the BNB concentration and its ζ-potential were about 2.94 × 108 particles/mL and -20 mV, respectively (24 h after BNB generation with a mixing time of 120 min). This indicates the continued existence and stability of BNBs in water for an extended period of time.

Secretagogin affects insulin secretion in pancreatic ß-cells by regulating actin dynamics and focal adhesion.

Secretagogin (SCGN), a Ca(2+)-binding protein having six EF-hands, is selectively expressed in pancreatic ß-cells and neuroendocrine cells. Previous studies suggested that SCGN enhances insulin secretion by functioning as a Ca(2+)-sensor protein, but the underlying mechanism has not been elucidated. The present study explored the mechanism by which SCGN enhances glucose-induced insulin secretion in NIT-1 insulinoma cells. To determine whether SCGN influences the first or second phase of insulin secretion, we examined how SCGN affects the kinetics of insulin secretion in NIT-1 cells. We found that silencing SCGN suppressed the second phase of insulin secretion induced by glucose and H2O2, but not the first phase induced by KCl stimulation. Recruitment of insulin granules in the second phase of insulin secretion was significantly impaired by knocking down SCGN in NIT-1 cells. In addition, we found that SCGN interacts with the actin cytoskeleton in the plasma membrane and regulates actin remodelling in a glucose-dependent manner. Since actin dynamics are known to regulate focal adhesion, a critical step in the second phase of insulin secretion, we examined the effect of silencing SCGN on focal adhesion molecules, including FAK (focal adhesion kinase) and paxillin, and the cell survival molecules ERK1/2 (extracellular-signal-regulated kinase 1/2) and Akt. We found that glucose- and H2O2-induced activation of FAK, paxillin, ERK1/2 and Akt was significantly blocked by silencing SCGN. We conclude that SCGN controls glucose-stimulated insulin secretion and thus may be useful in the therapy of Type 2 diabetes.

Lower Lid Laxity is Negatively Correlated with Improvement of the Ocular Surface Disease Index in Dry Eye Treatment.

PURPOSE: To compare the responses to dry eye treatment of patients sorted by the degree of lower lid laxity. METHODS: Sixty patients were grouped into three groups according to the degree of lower lid laxity. Tear break-up time (TBUT), Schirmer test (ST) scores, ocular surface disease index (OSDI) scores, and changes in OSDI score in each group were compared, before and at 3 months after treatment. RESULTS: TBUT, ST, and OSDI scores were not different among the three groups at baseline. TBUT improved in each group at 3 months after treatment, and no differences between groups were found. ST scores were not increased after treatment, while OSDI were improved to 22.57 ± 5.243, 31.16 ± 11.353, and 37.85 ± 13.342 in the no, moderate, and high laxity groups, respectively; these improvements were statistically significant (p = 0.003, <0.001, <0.001, respectively). Patients with greater than moderate lower lid laxity saw the smallest improvement in response to dry eye treatment, as assessed by change in OSDI score (p = 0.005 versus moderate laxity group, p = 0.005 versus no laxity group). CONCLUSIONS: Lower lid laxity is one of the factors contributing to the responses to dry eye treatment assessed by change in OSDI score, independent of TBUT and ST scores.

Feasibility of islet magnetic resonance imaging using ferumoxytol in intraportal islet transplantation.

There is a clinical need for an alternative labeling agent for magnetic resonance imaging (MRI) in islet transplantation. We aimed to evaluate the feasibility of islet MRI using ferumoxytol, which is the only clinically-available ultrasmall superparamagnetic iron oxide. We compared islet function and viability of control islets and islets labeled with ferumoxytol and/or a heparin-protamine complex (HPF). Efficacy of ferumoxytol labeling was assessed in both ex vivo and in vivo models. Labeling for 48 h with HPF, but not up to 800 µg/mL ferumoxytol, deranged ex vivo islet viability and function. The T2∗ relaxation time was optimal when islets were labeled with 800 µg/mL of ferumoxytol for 48 h. Prussian blue stain, iron content assay, transmission electron microscopy (TEM) supported internalization of ferumoxytol particles. However, the labeling intensity in the ex vivo MRI of islets labeled with ferumoxytol was much weaker than that of islets labeled with ferucarbotran. In syngeneic intraportal islet transplantation, there was a correlation between the total area of visualized islets and the transplanted islet mass. In conclusion, islet MRI using ferumoxytol was feasible in terms of in vitro and in vivo efficacy and safety. However, the weak labeling efficacy is still a hurdle for the clinical application.

Co-culture with mature islet cells augments the differentiation of insulin-producing cells from pluripotent stem cells.

Islet transplantation has been hampered by the shortage of islet donors available for diabetes therapy. However, pluripotent stem cells (PSCs) can be an alternative source of insulin-producing cells (IPCs) because of their capacity for self-renewal and differentiation. We described a method to efficiently differentiate PSCs into IPCs by co-culturing mature islets with directed-differentiated pancreatic endoderm (PE) cells from mouse and human PSCs. PE cells co-cultured with islet cells or islet cell-derived conditioned medium (CM) showed increased expression levels of ß-cell markers; significantly higher levels of proinsulin- and Newport Green (NG)-positive cells, which revealed the characteristics of insulin producing cells; and increased insulin secretion upon glucose stimulation. Co-culturing human PE cells with islet cells was also effective to differentiate PE cells into IPCs. Diabetic nude mice transplanted with co-cultured cells exhibited restored euglycemia, human C-peptide release, and improved glucose tolerance. Immunohistochemistry revealed that insulin+/C-peptide + cells existed in the grafted tissues. These results suggest that mature islet cells can increase the differentiation efficiency of PE cells into mature IPCs via paracrine effects.

Efficacy of Additional Glaucoma Drainage Device Insertion in Refractory Glaucoma: Case Series with a Systematic Literature Review and Meta-Analysis.

PURPOSE: To report the efficacy of additional glaucoma drainage device (GDD) insertion in eyes with refractory glaucoma and which have a failed primary GDD. METHODS: We conducted a non-comparative, retrospective study on eight eyes of eight patients who had a failed primary GDD and received an additional GDD in the same eye. Intraocular pressure (IOP), visual acuity (VA), the number of anti-glaucomatous medications, and complications were analyzed during the most recent office visit. Success was defined as an IOP between 6 and 21 mmHg and a 20% decrease in IOP after additional GDD insertion, with or without anti-glaucomatous medication. RESULTS: The mean decrease in IOP at the final follow-up was 19.3 mmHg (56.1%). The mean number of anti-glaucomatous medications used at the final follow-up (2.38) was significantly less than the preoperative mean (3.50). Seven patients achieved the criteria for success, whereas one patient had an unsuccessful outcome because of corneal graft failure after additional GDD insertion. CONCLUSIONS: We showed that after the failure of a primary GDD, an additional GDD offered favorable IOP control and stable VA. In agreement with a review of previous literature, GDD insertion is the best option for treating refractory glaucoma, even in patients with a failed primary GDD.

Topographical Analysis of Non-Glaucomatous Myopic Optic Discs Using a Confocal Scanning Laser Ophthalmoscope (TopSS).

OBJECTIVES: To show normative data of optic discs and the mechanism of glaucoma in people with myopia. DESIGN: Cross-sectional study. PARTICIPANTS: This study investigated 89 Korean adults with myopia but without glaucoma. METHODS: Patients were divided into three groups according to the refractive error: low, moderate, and high; and axial length: normal or below normal length, moderately long, and extremely long. Optic disc variables were obtained by confocal scanning laser ophthalmoscope and compared among groups. RESULTS: The optic disc parameters have a correlation between the refractive error and the optic disc parameters such as average depth, volume below, and half-depth volume. Those parameters also decreased as the axial length increased. The thickness of the volume above decreased significantly as the axial length increased, but a similar relationship was not evident with the refractive error change. In addition, the optic disc parameters were analyzed with respect to the 12 clockwise directions. CONCLUSIONS: Analyses of optic disc parameters provided by TopSS™ revealed the height of the disc decreased as the myopic refractive error and/or axial length increased. The RNFL bundle became compacted in the thinner disc of the myopic population. This could be an explanation for the fragility of the RNFL in the myopic population. The 12 radial section analyses revealed the shallow cupping at the temporal side in the high-myopic, very-long-axis group. The neuroretinal rim (NRR) height significantly decreased at the superior and inferior sides. These findings suggest that the RNFL bundle should be under high mechanical strain in these sectors.

Benefits of PEGylation in the early post-transplant period of intraportal islet transplantation as assessed by magnetic resonance imaging of labeled islets.

While a few studies have demonstrated the benefit of PEGylation in islet transplantation, most have employed renal subcapsular models and none have performed direct comparisons of islet mass in intraportal islet transplantation using islet magnetic resonance imaging (MRI). In this study, our aim was to demonstrate the benefit of PEGylation in the early post-transplant period of intraportal islet transplantation with a novel algorithm for islet MRI. Islets were PEGylated after ferucarbotran labeling in a rat syngeneic intraportal islet transplantation model followed by comparisons of post-transplant glycemic levels in recipient rats infused with PEGylated (n = 12) and non-PEGylated (n = 13) islets. The total area of hypointense spots and the number of hypointense spots larger than 1.758 mm(2) of PEGylated and non-PEGylated islets were quantitatively compared. The total area of hypointense spots (P < 0.05) and the number of hypointense spots larger than 1.758 mm(2) (P < 0.05) were higher in the PEGylated islet group 7 and 14 days post translation (DPT). These results translated into better post-transplant outcomes in the PEGylated islet group 28 DPT. In validation experiments, MRI parameters obtained 1, 7, and 14 DPT predicted normoglycemia 4 wk post-transplantation. We directly demonstrated the benefit of islet PEGylation in protection against nonspecific islet destruction in the early post-transplant period of intraportal islet transplantation using a novel algorithm for islet MRI. This novel algorithm could serve as a useful tool to demonstrate such benefit in future clinical trials of islet transplantation using PEGylated islets.

Amyloidogenic peptide oligomer accumulation in autophagy-deficient ß cells induces diabetes.

Islet amyloid accumulation is a hallmark of human type 2 diabetes (T2D). In contrast to human islet amyloid polypeptide (hIAPP), murine islet amyloid polypeptide (mIAPP) does not exhibit amyloidogenic propensity. Because autophagy is important in the clearance of amyloid-like proteins, we studied transgenic mice with ß cell-specific expression of hIAPP to evaluate the contribution of autophagy in T2D-associated accumulation of hIAPP. In mice with ß cell-specific expression of hIAPP, a deficiency in autophagy resulted in development of overt diabetes, which was not observed in mice expressing hIAPP alone or lacking autophagy alone. Furthermore, lack of autophagy in hIAPP-expressing animals resulted in hIAPP oligomer and amyloid accumulation in pancreatic islets, leading to increased death and decreased mass of ß cells. Expression of hIAPP in purified monkey islet cells or a murine ß cell line resulted in pro-hIAPP dimer formation, while dimer formation was absent or reduced dramatically in cells expressing either nonamyloidogenic mIAPP or nonfibrillar mutant hIAPP. In autophagy-deficient cells, accumulation of pro-hIAPP dimers increased markedly, and pro-hIAPP trimers were detected in the detergent-insoluble fraction. Enhancement of autophagy improved the metabolic profile of hIAPP-expressing mice fed a high-fat diet. These results suggest that autophagy promotes clearance of amyloidogenic hIAPP, autophagy deficiency exacerbates pathogenesis of human T2D, and autophagy enhancers have therapeutic potential for islet amyloid accumulation-associated human T2D.

Diabetes-free survival in patients who underwent islet autotransplantation after 50% to 60% distal partial pancreatectomy for benign pancreatic tumors.

BACKGROUND: Several retrospective studies with short-term follow-up have demonstrated a low rate of new-onset diabetes after distal pancreatectomy for benign pancreatic tumors. We sought to determine the long-term diabetes-free survival of patients who underwent islet autotransplantation (IAT) after distal pancreatectomy and to identify any associations between the isolation parameters of autologous islets and diabetes-free survival. METHODS: Among the 37 nondiabetic patients who underwent 50% to 60% partial pancreatectomy, 20 underwent IAT (IAT group; median follow-up period, 61 months). In the IAT group, diabetes-free survival was determined based on annual oral glucose tolerance tests, fasting blood glucose, and hemoglobin A1C. RESULTS: The 7-year diabetes-free survival rate was 51% in the IAT group (median follow-up period, 61 months) and 45% in the 37 study subjects. Diabetes-free survival was significantly prolonged when islet yield per gram of pancreas weight was more than 5154 islet equivalents (IEQ)/g, even in patients with prediabetes and high insulin resistance who had a markedly high rate of diabetes development. The proportion of patients with impaired glucose tolerance at 2 years after distal pancreatectomy was 12 of 16 in the control group, 6 of 7 in patients with islet yields of less than 5154 IEQ/g, and 3 of 11 in patients with islet yields of more than 5154 IEQ/g (P=0.019). CONCLUSIONS: Partial (50%-60%) pancreatectomy for benign pancreatic tumors had a major metabolic consequence, especially in patients with prediabetes and high insulin resistance. In this setting, prolonged diabetes-free survival was observed in patients who underwent IAT when a high islet yield per gram of pancreas was achieved.

An unusual case of an orbital abscess secondary to contralateral sinusitis.

Orbital complications secondary to acute rhinosinusitis can result in permanent blindness or death if not treated promptly and appropriately. Many authors have reported that almost all such patients had abscesses adjacent to the infected sinuses. However, the authors experienced an orbital abscess secondary to contralateral sinusitis. Here, the authors report an 8-year-old patient who had a left superior orbital abscess secondary to a right ethmoidomaxillary sinusitis.

Activin A, exendin-4, and glucose stimulate differentiation of human pancreatic ductal cells.

Islet transplantation is one treatment option for diabetes mellitus. However, novel sources of pancreatic islets or insulin-producing cells are required because the amount of donor tissue available is severely limited. Pancreatic ductal cells are an alternative source of ß-cells because they have the potential to differentiate into insulin-producing cells. We investigated whether treatment of human pancreatic ductal cells with activin A (ActA) and exendin-4 (EX-4) stimulated transdifferentiation of the cells, both in vitro and in vivo. We treated human pancreatic ductal cells with ActA and EX-4 in high-glucose media to induce differentiation into insulin-producing cells and transplanted the cells into streptozotocin-induced diabetic nude mice. Co-treatment of mice with ActA and EX-4 promoted cell proliferation, induced expression of pancreatic ß-cell-specific markers, and caused glucose-induced insulin secretion compared with the ActA or EX-4 mono-treatment groups respectively. When pancreatic ductal cells treated with ActA and EX-4 in high-glucose media were transplanted into diabetic nude mice, their blood glucose levels normalized and insulin was detected in the graft. These findings suggest that pancreatic ductal cells have a potential to replace pancreatic islets for the treatment of diabetes mellitus when the ductal cells are co-treated with ActA, EX-4, and glucose to promote their differentiation into functional insulin-producing cells.