Effects of Chronic Low-Dose Internal Radiation on Immune-Stimulatory Responses in Mice.

The Linear-No-Threshold (LNT) model predicts a dose-dependent linear increase in cancer risk. This has been supported by biological and epidemiological studies at high-dose exposures. However, at low-doses (LDR ≤ 0.1 Gy), the effects are more elusive and demonstrate a deviation from linearity. In this study, the effects of LDR on the development and progression of mammary cancer in FVB/N-Tg(MMTVneu)202Mul/J mice were investigated. Animals were chronically exposed to total doses of 10, 100, and 2000 mGy via tritiated drinking water, and were assessed at 3.5, 6, and 8 months of age. Results indicated an increased proportion of NK cells in various organs of LDR exposed mice. LDR significantly influenced NK and T cell function and activation, despite diminishing cell proliferation. Notably, the expression of NKG2D receptor on NK cells was dramatically reduced at 3.5 months but was upregulated at later time-points, while the expression of NKG2D ligand followed the opposite trend, with an increase at 3.5 months and a decrease thereafter. No noticeable impact was observed on mammary cancer development, as measured by tumor load. Our results demonstrated that LDR significantly influenced the proportion, proliferation, activation, and function of immune cells. Importantly, to the best of our knowledge, this is the first report demonstrating that LDR modulates the cross-talk between the NKG2D receptor and its ligands.

Interleukin-18 up-regulates amino acid transporters and facilitates amino acid-induced mTORC1 activation in natural killer cells.

Upon inflammation, natural killer (NK) cells undergo metabolic changes to support their high energy demand for effector function and proliferation. The metabolic changes are usually accompanied by an increase in the expression of nutrient transporters, leading to increased nutrient uptake. Among various cytokines inducing NK cell proliferation, the mechanisms underlying the effect of interleukin (IL)-18 in promoting NK cell proliferation are not completely understood. Here, we demonstrate that IL-18 is a potent cytokine that can enhance the expression of the nutrient transporter CD98/LAT1 for amino acids independently of the mTORC1 pathway and thereby induce a dramatic metabolic change associated with increased proliferation of NK cells. Notably, treatment of IL-18-stimulated NK cells with leucine activates the metabolic sensor mTORC1, indicating that the high expression of amino acid transporters induces amino acid-driven mTORC1 activation. Inhibition of the amino acid transporter CD98/LAT1 abrogated the leucine-driven mTORC1 activation and reduced NK cell effector function. Taken together, our study identified a novel role of IL-18 in up-regulating nutrient transporters on NK cells and thereby inducing metabolic changes, including the mTORC1 activation by amino acids.

Face Lift Using Dual Deep Tissue Support.

BACKGROUND: Utilizing the concept of Barton's high superficial musculo-aponeurotic system (SMAS) technique, the authors performed the more extensive skin-attached SMAS/platysma flap elevation and the 'dual deep tissue support' technique involving multiple plications of the parotid-masseteric fascia, repositioning of the SMAS, and platysma muscle. Our aim was to demonstrate a specific surgical procedure for face and neck lift and offer its pitfalls and outcomes. METHODS: This study included 83 patients aged between 54 and 73 years. The pre- and 10-month postoperative photographs of all patients were used to assess the extent of the nasolabial folds, the labiomental fold, and the cervical band (platysma band). Each patient's subjective aesthetic satisfaction was also evaluated. RESULTS: At 3 and 6 months postoperatively, 94% (n = 3) of patients achieved "minimal" and "mild" nasolabial folds. Most patients (89.1%, n = 74) were satisfied with their outcomes. Two minor hematomas (2.4%) occurred locally over the temporal or retro-auricular area. No incidence of skin flap necrosis or permanent facial nerve injury was observed. CONCLUSIONS: Our extensive skin-attached SMAS/platysma flap elevation with dual deep tissue support, both by multiple parotic masseteric plication and SMAS/platysma repositioning, provided not only the definite lifting effect in the immediate postoperative period, but also resulted in long-lasting lifting outcomes without remission. LEVEL OF EVIDENCE: IV.

Does posterior tibial slope affect the results of conservative treatment for anterior cruciate ligament tears?

OBJECTIVE: To evaluate the association between posterior tibial slope (PTS) and the short-term results of conservative treatment for the patients with anterior cruciate ligament (ACL) tears. METHODS: Thirty-seven patients (37 knees: male 33, female 4) who were managed with the same treatment protocols for ACL tears were included. All patients applied ACL brace and underwent standardized rehabilitation protocol. Group A consisted of 14 patients with successful results after conservative management and group B consisted of 23 patients who received operative treatments due to failed conservative management. For each group, a plain radiograph was used to measure the PTS. The demographic data of patients and differences of PTS between each group were analyzed. RESULTS: The mean age was 33.2 years in group A and 29.7 years in group B, respectively (p = 0.8). There was no significant difference between each group in terms of gender, body mass index, and injury mechanism. There was no significant difference between each group in the classification according to the isolated or combined injury (p = 0.83). The mean PTS was 8.3° in group A and 10.2° in group B. The mean PTS in group A was significantly lower than that in group B (p = 0.03). CONCLUSIONS: The patients with successful results after conservative management had a lower mean PTS than those with failed conservative treatment (8.3° vs. 10.2°, p = 0.03). The failure of conservative treatment after ACL tear was found to be associated with increased PTS.

Nucleosome Presence at AML-1 Binding Sites Inversely Correlates with Ly49 Expression: Revelations from an Informatics Analysis of Nucleosomes and Immune Cell Transcription Factors.

Beyond its role in genomic organization and compaction, the nucleosome is believed to participate in the regulation of gene transcription. Here, we report a computational method to evaluate the nucleosome sensitivity for a transcription factor over a given stretch of the genome. Sensitive factors are predicted to be those with binding sites preferentially contained within nucleosome boundaries and lacking 10 bp periodicity. Based on these criteria, the Acute Myeloid Leukemia-1a (AML-1a) transcription factor, a regulator of immune gene expression, was identified as potentially sensitive to nucleosomal regulation within the mouse Ly49 gene family. This result was confirmed in RMA, a cell line with natural expression of Ly49, using MNase-Seq to generate a nucleosome map of chromosome 6, where the Ly49 gene family is located. Analysis of this map revealed a specific depletion of nucleosomes at AML-1a binding sites in the expressed Ly49A when compared to the other, silent Ly49 genes. Our data suggest that nucleosome-based regulation contributes to the expression of Ly49 genes, and we propose that this method of predicting nucleosome sensitivity could aid in dissecting the regulatory role of nucleosomes in general.

Enhanced light extraction efficiency in organic light-emitting diode with randomly dispersed nanopattern.

An optical scattering layer composed of randomly dispersed nanopatterns (RDNPs) was introduced in an organic light-emitting diode (OLED) to increase the out-coupling efficiency. An RDNP was fabricated by direct printing on a glass substrate. Owing to its low haze and high transmittance, the RDNP acted as a light extraction layer in the OLED. The RDNP OLEDs showed higher current density and luminance than the reference devices at the same voltage. The current and power efficiencies of the RDNP OLED increased by 25% and 34%, respectively, without electrical degradation. Furthermore, the RDNP devices achieved an external quantum efficiency of 27.5% at 1 mA/cm².

Uniformly embedded silver nanomesh as highly bendable transparent conducting electrode.

Ag-nanomesh-based highly bendable conducting electrodes are developed using a combination of metal nanotransfer printing and embossing for the 6-inch wafer scale. Two Ag nanomeshes, including pitch sizes of 7.5 and 10 µm, are used to obtain highly transparent (approximately 85% transmittance at a wavelength of 550 nm) and electrically conducting properties (below 10 Ω sq(-1)). The Ag nanomeshes are also distinguished according to the fabrication process, which is called transferred or embedded Ag nanomesh on polyethylene terephthalate (PET) substrate, in order to compare their stability against bending stress. Then the enhancement of bending stability when the Ag nanomesh is embedded in the PET substrate is confirmed.

Enhancement of light extraction efficiency of OLEDs using Si3N4-based optical scattering layer.

An optical scattering layer, consisting of a Si3N4 nano-pillar array and a spin-coated hydrogen silsesquioxane (HSQ) planarization layer, was introduced to an organic light-emitting diode (OLED) substrate to increase the out-coupling efficiency. After plasma enhanced chemical vapor deposition (PECVD) of the Si3N4 layer, the nano-pillar array was created using nanoimprint lithography and reactive ion etching. As the Si3N4 pillar array has a refractive index of 2.0, photons generated in the organic layer are scattered by the Si3N4 structures and thus have a higher chance of being emitted from the device. The spin-coated HSQ planarization layer produces a flat substrate, which is essential for depositing a uniform organic material layer and assuring the electric conductivity of the transparent conducting oxide (TCO) layer. In this study, Si3N4 nano-structures with a height of 100 or 300 nm were used to enhance the out-coupling efficiency of the OLED devices. Although the electrical conductivity of the TCO layer deposited on the light scattering layer was slightly degraded, the OLED devices formed with the light scattering layer exhibited a higher luminous power at given electrical power. Consequently, the use of a planarized 300-nm-thick Si3N4 layer increased the external quantum efficiency of the OLED device by 50% at 10,000 cd/m2 compared to the reference OLED device fabricated on a flat glass substrate.

Enhanced light extraction efficiency in organic light emitting diodes using a tetragonal photonic crystal with hydrogen silsesquioxane.

We report an organic light emitting diode (OLED) with a hydrogen silsesquioxane as a scattering material, for enhancing light extraction efficiency. A tetragonal photonic crystal was used as pattern type, and fabricated using a direct printing technique. Planarization was accomplished using TiO2 solgel solution, having a refractive index identical to that of the indium zinc oxide transparent electrode. The current efficiency and power efficiency of the OLED increased by 17.3% and 43.4% at 10 mA/cm², respectively, without electric degradation.

Genetic status of Asiatic black bear (Ursus thibetanus) reintroduced into South Korea based on mitochondrial DNA and microsatellite loci analysis.

The Asiatic black bear is one of the most endangered mammals in South Korea owing to population declines resulting from human exploitation and habitat fragmentation. To restore the black bear population in South Korea, 27 bear cubs from North Korea and Russian Far East (Primorsky Krai) were imported and released into Jirisan National Park, a reservoir of the largest wild population in South Korea, in 2004. To monitor the success of this reintroduction, the genetic diversity and population structure of the reintroduced black bears were measured using both mitochondrial and nuclear DNA markers. Mitochondrial D-loop region DNA sequences (615 bp) of 43 Japanese black bears from previous study and 14 Southeast Asian black bears in this study were employed to obtain phylogenetic inference of the reintroduced black bears. The mitochondrial phylogeny indicated Asiatic black bear populations from Russian Far East and North Korea form a single evolutionary unit distinct from populations from Japan and Southeast Asia. Mean expected heterozygosity (H(E)) across 16 microsatellite loci was 0.648 for Russian and 0.676 for North Korean populations. There was a moderate but significant level of microsatellite differentiation (F(ST) = 0.063) between black bears from the 2 source areas. In addition, genetic evidences revealed that 2 populations are represented as diverging groups, with lingering genetic admixture among individuals of 2 source populations. Relatedness analysis based on genetic markers indicated several discrepancies with the pedigree records. Implication of the phylogenetic and genetic evidences on long-term management of Asiatic black bears in South Korea is discussed.

Exploring a Drosophila Transcription Factor Interaction Network to Identify Cis-Regulatory Modules.

Multiple transcription factors (TFs) bind to specific sites in the genome and interact among themselves to form the cis-regulatory modules (CRMs). They are essential in modulating the expression of genes, and it is important to study this interplay to understand gene regulation. In the present study, we integrated experimentally identified TF binding sites collected from published studies with computationally predicted TF binding sites to identify Drosophila CRMs. Along with the detection of the previously known CRMs, this approach identified novel protein combinations. We determined high-occupancy target sites, where a large number of TFs bind. Investigating these sites revealed that Giant, Dichaete, and Knirp are highly enriched in these locations. A common TAG team motif was observed at these sites, which might play a role in recruiting other TFs. While comparing the binding sites at distal and proximal promoters, we found that certain regulatory TFs, such as Zelda, were highly enriched in enhancers. Our study has shown that, from the information available concerning the TF binding sites, the real CRMs could be predicted accurately and efficiently. Although we only may claim co-occurrence of these proteins in this study, it may actually point to their interaction (as known interaction proteins typically co-occur together). Such an integrative approach can, therefore, help us to provide a better understanding of the interplay among the factors, even though further experimental verification is required.

Open-Door Laminoplasty Using Lateral Mass Anchoring Screws and Nonabsorbable Sutures in Patients with Multilevel Cervical Myelopathy.

BACKGROUD: The purpose of this study was to evaluate the clinical usefulness of open-door laminoplasty using lateral mass anchoring screws and nonabsorbable sutures (ODLLM) for multilevel cervical myelopathy. METHODS: We retrospectively studied 30 patients who underwent ODLLM. Clinical evaluations were performed using a visual analog scale (VAS), Japanese Orthopaedic Association (JOA) score, and Neck Disability Index (NDI) preoperatively, at 1 year postoperatively, and at the last follow-up. Radiographic evaluation was done using cervical spine radiographs to measure changes in the lordotic angle and range of motion (ROM) preoperatively, at 1 year postoperatively, and at the last follow-up and computed tomography at 1 year postoperatively to measure the opening angle and anteroposterior diameter of the spinal canal. RESULTS: Significant improvement in VAS, JOA, and NDI was seen overall at 1 year after operation. However, there was no significant difference between 1 year after operation and the last follow-up. There were no significant changes in the lordotic angle and neck ROM. The mean opening angle of the opened lamina was measured as 39.04°. The mean anteroposterior diameter was significantly increased from 7.51 ± 1.79 mm before surgery to 13.98 ± 1.80 mm at 1 year of operation. Complications such as laminar reclosure and screw loosening were not observed in all cases. CONCLUSIONS: The ODLLM was technically easy to perform and showed good results comparable to those of conventional techniques. It can be suggested that ODLLM is an appropriate treatment option for multilevel cervical myelopathy.

Adjustment of N stages of gastric cancer by the ratio between the metastatic and examined lymph nodes.

BACKGROUND: The present study attempted to determine whether N stage could be adjusted for the differences in survival rates based on the ratio between the examined and metastatic lymph nodes (LN ratio). METHODS: Five hundred and twenty-nine patients with both >15 lymph nodes examined and >or= N1 after R0 resection were enrolled in the present study. To determine the cutoff LN ratio, the ratios at each N stage were compared at intervals of 10% with the log-rank test of Kaplan-Meier estimates of the survival curves. RESULTS: The 5-year survival rate of patients with N1 was 71.7%. Those of N2 patients with LN ratio of <60% (n = 116) and >or=60% (n = 3) were 37.0% and 0%, respectively. Those of N3 patients with LN ratio of <30% (n = 32), between 30% and 60% (n = 67), and >or=60% (n = 26) were 31.0%, 16.3%, and 0%, respectively. Thus, adjusted N2 was obtained from the sum of N2 < 60% and N3 < 30%. N3 with an LN ratio between 30% and 60% was regarded as adjusted N3. N2 and N3 patients with an LN ratio of >or=60% were regarded as adjusted T4. The 5-year survival rate in patients with adjusted N2, N3, and N4 were 35.7%, 16.3%, and 0%, respectively. Multivariate analysis showed adjusted N stage and tumor depth were significant independent prognostic factors. CONCLUSIONS: The results of this study suggest that, since stage migration can be induced in the N staging system, such stage migration can be adjusted by the LN ratio based on the survival rate.

Prognostic factors for survival in patients with hepatic recurrence after curative resection of gastric cancer.

BACKGROUND: This study was done to evaluate the prognostic factors that may affect the survival of patients with recurrent hepatic metastasis after curative resection of gastric cancer. METHODS: We reviewed the medical records of 73 patients with recurrent hepatic metastasis after surgical treatment of gastric cancer from January 1995 to December 2005. Prognostic factors were classified into three groups: primary tumor factors, recurrent hepatic factors, and treatment factors. The prognostic values of these factors were assessed using univariate and multivariate analyses by the log-rank test in the Kaplan-Meier method and Cox's proportional hazard model. RESULTS: The overall median survival rate of the 73 study patients was 20.0 months [95% confidence interval (CI) 15.4-24.6 months]. The median survival rate after diagnosis of recurrent hepatic metastasis was 5 months (95% CI 3.5-6.5 months). Univariate analysis showed that the favorable prognostic factors were stage I and II among the primary tumor factors, no extrahepatic metastasis and unilobar distribution among the recurrent hepatic factors, and radiofrequency ablation (RFA) +/- chemotherapy among the treatment factors when operative treatment had been excluded. The independent favorable prognostic factors revealed by the multivariate analysis were no extrahepatic metastasis and RFA +/- chemotherapy. The median survival rate of patients who had two favorable prognostic factors was 27 months (95% CI 0-66.38 months). CONCLUSIONS: Improvement in the survival rate can be expected with RFA +/- chemotherapy for patients with recurrent gastric cancer in the liver without extrahepatic metastasis.

Four cases of a cerebral air embolism complicating a percutaneous transthoracic needle biopsy.

A percutaneous transthoracic needle biopsy is a common procedure in the practice of pulmonology. An air embolism is a rare but potentially fatal complication of a percutaneous transthoracic needle biopsy. We report four cases of a cerebral air embolism that developed after a percutaneous transthoracic needle biopsy. Early diagnosis and the rapid application of hyperbaric oxygen therapy is the mainstay of therapy for an embolism. Prevention is the best course and it is essential that possible risk factors be avoided.

Snf2h Drives Chromatin Remodeling to Prime Upper Layer Cortical Neuron Development.

Alterations in the homeostasis of either cortical progenitor pool, namely the apically located radial glial (RG) cells or the basal intermediate progenitors (IPCs) can severely impair cortical neuron production. Such changes are reflected by microcephaly and are often associated with cognitive defects. Genes encoding epigenetic regulators are a frequent cause of intellectual disability and many have been shown to regulate progenitor cell growth, including our inactivation of the Smarca1 gene encoding Snf2l, which is one of two ISWI mammalian orthologs. Loss of the Snf2l protein resulted in dysregulation of Foxg1 and IPC proliferation leading to macrocephaly. Here we show that inactivation of the closely related Smarca5 gene encoding the Snf2h chromatin remodeler is necessary for embryonic IPC expansion and subsequent specification of callosal projection neurons. Telencephalon-specific Smarca5 cKO embryos have impaired cell cycle kinetics and increased cell death, resulting in fewer Tbr2+ and FoxG1+ IPCs by mid-neurogenesis. These deficits give rise to adult mice with a dramatic reduction in Satb2+ upper layer neurons, and partial agenesis of the corpus callosum. Mice survive into adulthood but molecularly display reduced expression of the clustered protocadherin genes that may further contribute to altered dendritic arborization and a hyperactive behavioral phenotype. Our studies provide novel insight into the developmental function of Snf2h-dependent chromatin remodeling processes during brain development.

Achieving three-dimensional lithium sulfide growth in lithium-sulfur batteries using high-donor-number anions.

Uncontrolled growth of insulating lithium sulfide leads to passivation of sulfur cathodes, which limits high sulfur utilization in lithium-sulfur batteries. Sulfur utilization can be augmented in electrolytes based on solvents with high Gutmann Donor Number; however, violent lithium metal corrosion is a drawback. Here we report that particulate lithium sulfide growth can be achieved using a salt anion with a high donor number, such as bromide or triflate. The use of bromide leads to ~95 % sulfur utilization by suppressing electrode passivation. More importantly, the electrolytes with high-donor-number salt anions are notably compatible with lithium metal electrodes. The approach enables a high sulfur-loaded cell with areal capacity higher than 4 mA h cm-2 and high sulfur utilization ( > 90 %). This work offers a simple but practical strategy to modulate lithium sulfide growth, while conserving stability for high-performance lithium-sulfur batteries.

Pulmonary paraganglioma manifesting as an endobronchial mass.

Thoracic paragangliomas comprise only 1-2% of all paragangliomas, including the adrenal pheochromocytomas, and these tumors are mostly found in the mediastinal compartments (1). To the best of our knowledge, there is only one case report in the pathology literature of endobronchial involvement by a primary pulmonary paraganglioma (2). We report here on the CT and bronchoscopic findings of a case of pathologically proven endobronchial paraganglioma in a 37-year-old woman. In our case, bronchoscopy and CT demonstrated an endobronchial hypervascular mass, which indicated the presence of carcinoid or hypervascular metastasis based on the known incidence of such tumors.

Spherical Macroporous Carbon Nanotube Particles with Ultrahigh Sulfur Loading for Lithium-Sulfur Battery Cathodes.

A carbon host capable of effective and uniform sulfur loading is the key for lithium-sulfur batteries (LSBs). Despite the application of porous carbon materials of various morphologies, the carbon hosts capable of uniformly impregnating highly active sulfur is still challenging. To address this issue, we demonstrate a hierarchical pore-structured CNT particle host containing spherical macropores of several hundred nanometers. The macropore CNT particles (M-CNTPs) are prepared by drying the aerosol droplets in which CNTs and polymer particles are dispersed. The spherical macropore greatly improves the penetration of sulfur into the carbon host in the melt diffusion of sulfur. In addition, the formation of macropores greatly develops the volume of the micropore between CNT strands. As a result, we uniformly impregnate 70 wt % sulfur without sulfur residue. The S-M-CNTP cathode shows a highly reversible capacity of 1343 mA h g-1 at a current density of 0.2 C even at a high sulfur content of 70 wt %. Upon a 10-fold current density increase, a high capacity retention of 74% is observed. These cathodes have a higher sulfur content than those of conventional CNT hosts but nevertheless exhibit excellent performance. Our CNTPs and pore control technology will advance the commercialization of CNT hosts for LSBs.

Synthesis of carbon-nitrogen nanostructures by hot isostatic pressure apparatus and their field emission properties.

Carbon-nitrogen (CN) nanofibers were synthesized in argon-nitrogen gas mixture at 75 MPa by high isostatic pressure (HIP) apparatus using a graphite resistive heater. The CN nanofibers were grown in random with the diameter of about 200 nm and the length over 5 microm. The structures obtained can be divided bamboo-like, spring-like, and bead necklace-like CN nanofibers. The nitrogen content of up to 8.4% was found in CN nanofibers by EELS analysis. Field emission results showed that the density of field emitters and the field enhancement factors changed by surface treatments and that CN nanofibers contained glass frit. The screen-printed CN nanofiber had a turn-on field of 2 V/microm.