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Antihuman T-lymphocyte immune globulin (ATG) was shown to lower the incidence of chronic graft-versus-host disease (cGVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) from an unrelated donor. The type, dose, and duration of ATG treatment is a matter of ongoing controversy in allo-HSCT. Furthermore, there has been no phase 3 study to explore the role of ATG-thymoglobulin for the prevention of cGVHD in allo-HSCT from matched siblings, whereas results from a recent randomized trial of ATG-Fresenius was reported (NEJM 2016). We performed a prospective, single-center, open-label, randomized trial of ATG-thymoglobulin as a part of the conditioning regimen. The primary endpoint was the cumulative incidence (CI) of cGVHD at a 2-year evaluation. A total of 126 patients with acute leukemia were planned to be enrolled and assigned randomly at a 1:1 ratio to receive ATG-thymoglobulin (1.25 mg/kg at three and two days before allo-HSCT) or receive no ATG-thymoglobulin stratified according to the refined Disease Risk Index and conditioning intensity. Both groups were well balanced for NCCN risk, disease type, disease status, and MRD status at HSCT. The current study finally enrolled 120 patients with a median of 560 days of follow-up (range 52 - 1257). The CI of cGVHD in the ATG group (n=60) and non-ATG (n=60) group at 2 years after allo-HSCT was 37.2% and 82.7%, respectively (p In conclusion, the current study revealed that the use of ATG-thymoglobulin, even at a relatively low dose (2.5 mg/kg), decreases the occurrence of cGVHD at a cost of an increased risk for relapse in the setting of allo-HSCT from matched sibling donors for acute leukemia. The optimal dose, timing, and duration of ATG-thymoglobulin should be investigated further. Disclosures Kim: BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Sun Pharma.: Research Funding; ILYANG: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Research Funding, Speakers Bureau; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Takeda: Research Funding. Lee:Alexion Pharmaceuticals Inc.: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Kim:Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; AML Global Portal: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Hanmi: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; BL&H: Research Funding; Astellas: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Chugai: Consultancy, Honoraria; Amgen Inc.: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Yuhan: Consultancy, Honoraria; SL VaxiGen: Consultancy, Honoraria; AbbVie: Honoraria; Sanofi-Genzyme: Honoraria; Daiichi Sankyo: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees.

This study investigated the effect of post-weld processes including annealing and drawing on the microstructure and mechanical properties of high-Mn steel pipes welded by gas tungsten arc welding. The weld metal showed a solidified microstructure having coarse and elongated grains due to coalescence of columnar dendrite into welding heat direction. After post-annealing, the solidified microstructure changed into equiaxed grains due to recrystallization and grain growth. Mn segregation occurred during welding solidification and caused lower stacking fault energy (SFE) in the Mn-depleted region. Although &epsilon, martensite formation in the as-welded state and during deformation was expected due to decreased SFE of the Mn-depleted zone, all regions showed a fully austenitic phase. The annealing process decreased strength due to grain coarsening but increased ductility. The drawing process increased strength of weld metal through work hardening. All pipes showed decreasing strain rate sensitivity (SRS) with deformation and negative SRS after certain strain levels. It was confirmed that negative SRS is related to less formation of mechanical twinning at a higher strain rate. This work provides fundamental insights into manufacturing a high-Mn steel pipe and manipulating its properties with annealing and drawing processes.

Introduction: Accurate prediction of non-small cell lung cancer (NSCLC) prognosis after surgery is still challenging. Cox proportional hazard model is widely used, but there are some limitations like proportional hazard assumption, computational complexity, and unspecified time component. In this study, we developed the novel neural network models using 30 clinicopathological features of surgically resected NSCLC patients. Materials and Methods: We analyzed a dataset of training cohorts of 1,034 patients and external validation cohort of 303 patients, and compared the novel neural network model and Cox PH model to predict 3-year recurrence of the patient. Results: We developed deep neural network for binned time survival analysis (DeepBTS) algorithm, which use root-mean-squared error (supervised learning model, s- DeepBTS) or negative log-likelihood (semi-unsupervised learning model, su- DeepBTS) as loss function. The su-DeepBTS algorithm showed the improved performance (C-index, 0.7166; AUC, 0.7606) compared to other models (Cox PH: 0.6861 and 0.7185; s-DeepBTS: 0.6926 and 0.7250, respectively). Top 10 features was selected from su-DeepBTS model and su-DeepBTS selector pair: the number of lymph node metastasis, tumor size, histologic subtype, vascular invasion, R0 resection, neoadjuvant /adjuvant treatment, and performance status of patients. These features distinguished low and high-risk group in the training cohort (p = 4.25×10-5) and the validation cohort (p = 1.07×10-11). Conclusions: The su-DeepBTS model using 10 selected features can predict the prognosis of resected NSCLC patients. We plan to diversify the input features by radiologic, pathological imaging and genomic data to integrate multimodal medical information and enhance the performance of this model using deep neural network. Citation Format: Ho Jung An, Bora Lee, Sang Hoon Chun, Ji Hyung Hong, In Sook Woo, Seoree Kim, Joon Won Jeong, Jae Jun Kim, Hyun Woo Lee, Sungsoo Park, Heejoon Jo, Yoon Ho Ko. DeepBTS: Prediction of recurrence-free survival of non-small cell lung cancer using time-binned deep neural network [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2091.

Introduction Histopathological images in high-powered contain quantitative information for tumor cell morphology, but humans could not sufficiently extract prognostic features of tumor cell morphology associated with tumor recurrence of patient. In this study, we developed and trained the DeepRePath model, a deep convolutional neural network (CNN), on histopathological images to predict the recurrence of resected lung adenocarcinoma (LUAD). Methods A total of 244 haematoxylin and eosin stained histopathology slides of resected LUAD patients were used to train and validate the DeepRePath model. We manually segmented a cancer region in a LUAD tissue slide and captured to an image. All images were captured at x400 magnification and split into 13,329 image patches. We trained the DeepRePath model by transfer learning using 13,329 image patches from 244 LUAD patients. Results 95 out of 244 patients developed recurrence after surgical resection. The DeepRePath model showed an average area under the curve (AUC) of 0.78 in 5-fold cross validation on the training cohort. We plan to employ external validation to evaluate the proposed model. In addition, using gradient-weighted class activation mapping (Grad-CAM), we confirmed that DeepRePath identified and used individual tumor cells with atypia to predict the recurrence of the patient. Conclusions DeepRePath model using transfer learning and CNN can accurately predict recurrence after curative resection of LUAD based on atypia of tumor cell. Citation Format: Yoon Ho Ko, Soon Auck Hong, Tae-Jung Kim, Ji Hyung Hong, Sang Hoon Chun, Seoree Kim, Ho Jung An, Sungsoo Park, Won Sang Shim. DeepRePath: Finding prognostic features of tumor cell on the histopathologic image of lung cancer using explainable deep convolutional neural network [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2093.

A pH-responsive poly(methacrylic acid) (PMAA) functionalized SBA-15 nanohybrid has been synthesized via free radical polymerization method. Furthermore, silver nanoparticles (Ag NPs) were impregnated to the polymerized SBA-15-PMAA by using co-reduction approach. The resultant AgNPs-SBA-15-PMAA catalyst was used for the reduction of various dyes using NaBH4 as the reducing agent. Compared to all other synthesized catalysts in this work as well as with the existing catalyst in the literatures, our synthesized AgNPs-SBA-15-PMAA catalyst showed significantly higher activity for the reduction of dyes due to the synergistic effect of Ag NPs and pH responsive PMAA. The effects of reaction parameters such as pH, amount of nanoparticles, and NaBH4 concentrations were also studied in detail to obtain the optimized condition for the reaction. The overall catalytic performance showed that the reduction reaction is more efficient under low pH. In addition, the catalyst could be re-used without obvious losses of catalytic activity at least more than five cycles.

This paper reports a one-pot sol–gel approach for the synthesis of the alkylammonium-functionalized mesoporous silica particles with hollow structures and mesoporous silica films via hydrothermal reaction through the self-assembly of N-trimethoxysilylpropyl-N,N,N-trimethylammonium chloride (TMAPS) and tetraethoxysilane (TEOS) as a silica source, dodecyldimethyl(3-sulfopropyl)ammonium hydroxide (DDAPS) and fluorocarbon anion (ammonium perfluorooctanoate (APFO)) as the structure-directing agent. The alkylammonium-functionalized hollow mesoporous silica particles exhibited a different morphology, mesoporosity, and hollow structure with a layered mesostructure in the shell according to the DDAPS/APFO surfactant molar ratios (DDAPS/APFO = 3/1~1/9 or APFO in the range of 10~80 mM), reaction times (6~48 h), and reaction temperatures (45~95 °C). Alkylammonium-functionalized hollow mesoporous silica particles with spherical morphologies were produced from precipitation in the bottom of the reaction bottle after the hydrothermal reaction. At a DDAPS/APFO surfactant ratio of 1/3, reaction temperature of 60 °C, and reaction times of 24 h and 48 h, the alkylammonium-functionalized hollow mesoporous silica spheres displayed a multilayered mesostructure in the shell. The sphere size could be controlled from ca. 76 nm to ca. 350 nm with a shell thickness of ca. 35 nm. In addition, alkylammonium-functionalized mesoporous silica films were produced at the air–water interface, whereas hollow mesoporous silica spheres were produced with precipitation in the bottom of the reaction bottle. The film thickness was controlled from ca. 210 nm to ca. 400 nm.

Patients undergoing hematopoietic stem cell transplantation (HSCT) frequently receive empiric antibiotics during the neutropenic period before engraftment. Several recent studies have shown that anaerobes in the intestine are important mediators of intestinal homeostasis, and that commensal bacteria can be potent modulators of the severity of acute graft-versus-host disease (aGVHD). However, the relationships among the type of antibiotic used during the neutropenic period, changes in the intestinal microbiota, and subsequent occurrence of aGVHD are not clear. In this study, a total of 211 patients undergoing HSCT were stratified into 3 groups: patients not treated with any antibiotics during the neutropenic period (group 1; n = 43), patients treated with cefepime only (group 2; n = 87), and patients treated with carbapenem antibiotics, defined as meropenem or prepenem with or without previous cefepime therapy (group 3; n = 81). Intestinal microbiota analyses were performed on pre- and post-HSCT stool samples, and immunophenotypic analyses were performed on pre- and post-HSCT peripheral blood samples. Among the 211 patients, 95 (45%) developed aGVHD (grade ≥II), including 54 with intestinal GVHD. The incidence of intestinal GVHD was higher in group 3 compared with group 1 and group 2 (32.1%, 11.6%, and 26.4%, respectively; P = .044). After adjusting for potentially significant variables identified by univariate analysis, multivariate analyses identified broad-spectrum antibiotic use during the neutropenic period as associated with the occurrence of intestinal GVHD (hazard ratio, 3.25; 95% confidence interval, 1.13 to 9.34; P = .029). Accordingly, loss of bacterial diversity in terms of alterations in intestinal microbiota after HSCT was observed in patients who received broad-spectrum antibiotics. Moreover, alterations in the frequencies of several intestinal bacteria phyla were associated with the occurrence of intestinal GVHD. Evaluation of circulating immune cell subsets according to type of antibiotic used during the neutropenic period revealed delayed recovery of myeloid-derived suppressor cells in the broad-spectrum antibiotic use group. Our data indicate that the use of broad-spectrum antibiotics during the neutropenic period is associated with a higher incidence of intestinal GVHD via loss of microbiome diversity. Further studies are needed to determine whether maintaining bacterial diversity can help prevent the development of aGVHD.

Background The aim of this study is to evaluate the prognostic impact of myeloid-derived suppressor cells (MDSCs) in multiple myeloma (MM) in the context of autologous stem cell transplantation (ASCT). Methods Peripheral blood samples were collected for measuring monocytic (M-) MDSCs (CD14posHLA-DRlow/neg) and early-stage (E-) MDSCs (LinnegHLA-DRnegCD33posCD11bpos) before and after ASCT. Clinical outcomes following ASCT differed according to the frequency of each MDSC phenotype. Results In the pre-ASCT analyses, lower M-MDSCs (

A phase I/II trial was conducted to explore the safety and activity of the addition of bortezomib on days -6, -3, and +1 relative to the day of autologous stem cell transplantation (ASCT) to a conditioning regimen with busulfan and melphalan (BuMel; 3.2 mg/kg/day busulfan on days -5 to -3 and 140 mg/m2/day melphalan on day -2) in patients with multiple myeloma (MM) following bortezomib-based induction chemotherapy. In phase I, doses of bortezomib (.7, 1.0, and 1.3 mg/m2) with BuMel were administered to groups of 3 patients each. No dose-limiting toxicities were observed. The maximum tolerated dose of bortezomib was 1.3 mg/m2/day. A subsequent cohort with 41 patients was analyzed in a phase II trial to identify safety and efficacy. The phase II trial showed a 75% response rate, including very good partial response (VGPR) or better, and a 55% rate of complete response (CR) at 3 months; For post-transplantation best response, an 83% rate of VGPR or better (68% CR) was observed. With a median follow-up of 31.4 months, the median progression-free survival (PFS) was 26.8 months. The probability of 2 year-PFS was 56.5%, and median overall survival (OS) could not calculated. Specifically, high-risk cytogenetics were associated with adverse survival outcomes compared with standard-risk cytogenetics (median PFS, 12.2 months versus 35.7 months, P = .039; median OS, 26.7 months versus 73.3 months; P = .086). With a median of 11 days to neutrophil engraftment and 10 days for platelet engraftment, no graft failure or delayed engrafting were observed. The most common grade 3 or severe nonhematologic adverse events included neutropenic fever (73.2%) and stomatitis (14.6%). Except for 3 patients with transplantation-related mortality due to sepsis, other adverse events were manageable. These findings demonstrate that bortezomib is safe and has a potential role in conditioning regimens in combination with BuMel for patients with transplantation-eligible MM.

The incidence of a secondary solid malignancy after hematopoietic cell transplantation (HCT) is increasing in long-term survivors. The aim of this study was to compare the clinicopathological characteristics of HCT recipients with secondary thyroid cancer (STC), with those of non-HCT thyroid cancer patients. We retrospectively investigated 5184 patients who received HCT between 1983 and 2016. Of these, 18 patients developed STC and underwent thyroidectomy due to differentiated thyroid cancer. We compared the clinicopathological characteristics of post-HCT thyroid cancer patients (post-HCT group) with those of a primary differentiated thyroid carcinoma cohort (cohort group) from Seoul St. Mary’s Hospital. The mean ages at HCT and thyroidectomy after HCT were 22.0 and 31.8 years, respectively, and the median time interval between HCT and thyroidectomy was 5 years (range 1–16). Compared with the cohort group, the post-HCT group was younger at cancer onset and frequently had a palpable mass at initial diagnosis. The post-HCT group had more aggressive features, including larger tumor size, frequent extrathyroidal extension, lymphatic invasion, perineural invasion, and frequent lateral neck node metastasis and distant metastasis, relative to the cohort group; however, most patients (83.2%) in the post-HCT group were stage I or II. Additionally, BRAF V600E mutation was less frequent in the post-HCT group. We found that STC after HCT showed younger presentation and more aggressive clinical presentation. Therefore, a policy of regular screening, including neck ultrasound examination, may promote early detection and treatment in HCT recipients.

This chapter deals with PMOs for adsorption. We discuss metal ions adsorption such as adsorption of Li+, Co2+, Hg2+, Pb2+, Cd2+, and Ag2+ ions. We also describe pollutant (organic molecules) adsorption and biomolecule adsorption such as protein, enzyme, amino acids and cell adhesion.

In this chapter, we overview important aspects and points in each chapter. Also we discuss on the future of the research and applications of PMOs with suggesting future direction of R&D on the development and applications of PMOs.

In this chapter, we describe PMOs as hosts for drug and biomolecules. Details include PMOs for drug delivery system, PMO as nanocarrier, hollow PMO, PMO with gatekeeper, PMOs for protein/gene delivery system, and biocompatibility of PMOs.

In this chapter, we deal with PMOs with a range of morphologies including powder, monolith, hollow, and film morphology, since the morphology is one of governing factors to control final physico-chemical properties of PMOs.

This chapter deals with the electronic and optical applications of PMOs such as electronic devices, low-k PMO films, and other optical applications including light harvesting, photoluminescence, and sensing and imprinting.

This chapter describes general synthetic routes of mesoporous materials, in particular, with focusing mesoporous silicas; Synthesis methods of mesoporous materials include sol-gel method, template assisted technique, liquid crystal template approach (LCTA), microwave assisted technique, and chemical etching technique. This chapter also deals with more details on the templates, basic and acidic synthesis, temperature, removal of template, nonaqueous synthesis, mesophase tailoring, morphology and modification of mesoporous silicas.

This chapter deals with the applications of PMOs as catalysts. Various PMOs for catalysts include organic group functionalized PMO materials and metal complex functionalized PMOs, where the metals used for complex functionalization include Pd, Ru, Pt, V, Ir, Mn, Cu, Rh, Mo, Sc, Ti, Fe, Cu, Sn, ferrocene, WO42−, and bimetal complex. Also metal nanoparticles supported PMOs will be discussed.

This chapter deals with the details of the synthesis of PMOs with what kind of precursors are used for the preparation of PMOs. Main precursors to be discussed include amorphous precursors, bis-silylate chiral precursors, metal complexes included in PMO Materials.

In this chapter, we deal with other advanced applications of PMOs such as ion exchangers, superhydrophilic antireflective coating, bioactive composites, refolding of proteins, and bioimaging.

In this chapter, we discuss the applications of PMOs for separation including gas separation and chromatographic phases.

The electronic deep level states of defects embedded in freestanding GaN crystals exfoliated from Si substrates by hydride vapour phase epitaxy (HVPE) is investigated for the first time, using deep level transient spectroscopy (DLTS). The electron traps are positioned 0.24 eV (E1) and 1.06 eV (E2) below the conduction band edge, respectively. The capture cross sections of E1 and E2 are evaluated to be 1.65 × 10−17 cm2 and 1.76 × 10−14 cm2 and the corresponding trap densities are 1.07 × 1014 cm−3 and 2.19 × 1015 cm−3, respectively. The DLTS signal and concentration of the electronic deep levels are independent of the filling pulse width, and the depth toward the bottom of the sample, evidenced by the fact that they are correlated to noninteracting point defects. Furthermore, Photoluminescence (PL) measurement shows green luminescence, suggesting that unidentified point defects or complex, which affect the optical characterisitics, exhibit. Despite the Si-based materials, the freestanding GaN exhibits deep level characteristics comparable to those of conventional freestanding GaN, suggesting that it is a desirable material for use in the next generation optoelectronic devices with the large-scalibilityand low production costs.

Background and objectives Cells of innate immunity normally recover in the first weeks to months after allogenenic hematopoietic stem cell transplantation (allo-HSCT). Their relevance in terms of graft-versus-host disease (GVHD) and graft-versus-leukemia (GVL) effect is largely unknown. The predictive role of early recovery in the immune cells on acute GVHD and GVL effect after allo-HSCT was investigated in patients with acute leukemia who achieved the first complete remission. Methods Peripheral blood samples were taken at the median of 14 days (range, 12∼29 days) after allo-HSCT. A cohort including 119 samples and characteristics of patients were analyzed. Immune cell populations were identified by flow cytometry. Results The median age was 49.0 years (range, 21∼69) at transplantation. Univariate analysis showed that age less than 40 years old, lower frequencies of CD8+ T cells, invariant natural killer T (iNKT) cells, monocytic myeloid derived suppressor cells (M-MDSCs) and higher frequency of immature MDSCs were associated with occurrence of grade III-IV acute GVHD. Multivariate analyses showed that iNKT cells (hazard ratio (HR), 0.453, 95% CI, 0.091∼0.844, p=0.024) and M-MDSCs (HR, 0.271, 95% CI, 0.078∼0.937, p=0.039) were independent factors. Combination of higher frequencies of both cell subsets was associated with lower incidence of grade III-IV acute GVHD, whereas patients with lower frequency of iNKT cells and higher frequency of M-MDSCs showed significant higher probability of relapse. Conclusions iNKT cells and M-MDSCs could be relevant cell biomarkers for predicting acute GVHD and/or relapse in acute leukemia patients treated with allo-HSCT.

Next-generation sequencing (NGS), which allows the simultaneous sequencing of billions of DNA fragments simultaneously, has revolutionized how we study genomics and molecular biology by generating genome-wide molecular maps of molecules of interest. However, the amount of information produced by NGS has made it difficult for researchers to choose the optimal set of genes. We have sought to resolve this issue by developing a neural network-based feature (gene) selection algorithm called Wx. The Wx algorithm ranks genes based on the discriminative index (DI) score that represents the classification power for distinguishing given groups. With a gene list ranked by DI score, researchers can institutively select the optimal set of genes from the highest-ranking ones. We applied the Wx algorithm to a TCGA pan-cancer gene-expression cohort to identify an optimal set of gene-expression biomarker candidates that can distinguish cancer samples from normal samples for 12 different types of cancer. The 14 gene-expression biomarker candidates identified by Wx were comparable to or outperformed previously reported universal gene expression biomarkers, highlighting the usefulness of the Wx algorithm for next-generation sequencing data. Thus, we anticipate that the Wx algorithm can complement current state-of-the-art analytical applications for the identification of biomarker candidates as an alternative method. The stand-alone and web versions of the Wx algorithm are available at https://github.com/deargen/DearWXpub and https://wx.deargendev.me/, respectively.

The AMP-activated protein kinase (AMPK) is a sensor of cellular energy status that has a dual role in cancer, i.e., pro- or anti-tumorigenic, depending on the context. In medulloblastoma, the most frequent malignant pediatric brain tumor, several in vitro studies previously showed that AMPK suppresses tumor cell growth. The role of AMPK in this disease context remains to be tested in vivo. Here, we investigate loss of AMPK&alpha, 2 in a genetically engineered mouse model of sonic hedgehog (SHH)-medulloblastoma. In contrast to previous reports, our study reveals that AMPK&alpha, 2 KO impairs SHH medulloblastoma tumorigenesis. Moreover, we performed complementary molecular and genomic analyses that support the hypothesis of a pro-tumorigenic SHH/AMPK/CNBP axis in medulloblastoma. In conclusion, our observations further underline the context-dependent role of AMPK in cancer, and caution is warranted for the previously proposed hypothesis that AMPK agonists may have therapeutic benefits in medulloblastoma patients. Note: an abstract describing the project was previously submitted to the American Society for Investigative Pathology PISA 2018 conference and appears in The American Journal of Pathology (Volume 188, Issue 10, October 2018, Page 2433).

Background The sensitivity of Philadelphia chromosome (Ph)-positive acute lymphoblastic leukemia (ALL) to reduced-intensity conditioning (RIC) allogeneic hematopoietic cell transplantation (HCT) versus myeloablative conditioning (MAC) allogeneic HCT by minimal residual disease (MRD) kinetics is not well established. Methods This study compared long-term outcomes based on MRD kinetics for 79 patients with RIC transplants and 116 patients with MAC transplants in first complete remission (CR1) after tyrosine kinase inhibitor-based chemotherapy (median follow-up, 67.1 months). MRD monitoring was centrally evaluated by real-time quantitative polymerase chain reaction for all patients. Results RIC showed a cumulative incidence of relapse (CIR; 30.6% vs 31.7%), nonrelapse mortality (17.5% vs 14.9%), disease-free survival (DFS; 51.9% vs 53.4%), and overall survival (61.1% vs 61.4%) comparable to those associated with MAC. In all MRD kinetics-based subgroups, no differences in CIR (early complete molecular response [CMR], 19.3% vs 4.8%; early major molecular response [MMR], 17.0% vs 26.8%; late CMR, 20.0% vs 14.3%; late MMR, 28.3% vs 31.0%; poor molecular response [PMR], 57.9% vs 62.4%) or DFS (early CMR, 71.6% vs 76.2%; early MMR, 66.9% vs 52.1%; late CMR, 50.0% vs 64.3%; late MMR, 50.7% vs 53.7%; PMR, 31.6% vs 34.1%) were observed between RIC and MAC. In a multivariate analysis, the conditioning intensity had no significant impact on transplantation outcomes. Conclusions RIC is a valid alternative choice for long-term disease control and is worthy of further investigation in prospective trials for adult Ph-positive ALL in CR1.

We report the growth of a 3.5 mm-thick bulk GaN layer using a stress-engineered homoepitaxy method without any external processes. We employ a gradient V/III ratio during the growth, which enables a 3.5 mm-thick bulk GaN layer with a smooth surface and high crystal quality to be obtained. For a constant V/III ratio of 10, the bulk GaN layer has a flat surface; however, microcracks emerge in the GaN layer. For a constant V/III ratio of 38, the bulk GaN layer has a rough surface, without microcracks. On the other hand, by decreasing the V/III ratio from 38 to 10, the structural properties of the GaN layers are successfully controlled. The higher V/III ratio in the initial growth stage leads to a rough surface, and reduced stress and dislocation density in the bulk GaN layers, while the lower V/III ratio in the second stage of the growth provides an opposite trend, confirmed by Raman spectroscopy and X-ray measurements. We expect that this study will offer a new opportunity to achieve the growth of high-crystallinity bulk GaN without ex situ and complicated processes.

Graphene oxide decorated with oxygen functional groups is a promising candidate as an active layer in resistive switching devices due to its controllable physical-chemical properties, high flexibility, and transparency. However, the origin of conductive channels and their growth dynamics remain a major challenge. We use in situ transmission electron microscopy techniques to demonstrate that nanoscale graphene oxide sheets bonded with oxygen dynamically change their physical and chemical structures upon an applied electric field. Artificially engineered bilayer reduced graphene oxide films with asymmetric oxygen content exhibit nonvolatile write-once-read-many memory behaviors without experiencing the bubble destruction due to the efficient migration of oxygen ions. We clearly observe that a conductive graphitic channel with a conical shape evolves from the upper oxygen-rich region to the lower oxygen-poor region. These findings provide fundamental guidance for understanding the oxygen motions of oxygen-containing carbon materials for future carbon-based nanoelectronics.

Graft-versus-host disease-free, relapse-free survival (GRFS) is a composite endpoint that measures survival free of relapse or significant morbidity after allogeneic hematopoietic stem cell transplantation (HSCT). Consecutive adult patients (N = 324) who received HSCT with fludarabine and busulfan-based conditioning for myelodysplastic syndrome (MDS) or secondary acute myeloid leukemia evolved from MDS were retrospectively analyzed. One-year and 3-year GRFS rates were 47.8% and 34.5%, respectively. Three fixed factors (circulating blast3%, high cytogenetic risk, and high comorbidity index) and 2 factors (which are) modifiable by clinicians (myeloablative conditioning [MAC] and low-dose [7.5 mg/kg] antithymocyte globulin [ATG]) were independent factors for poor GRFS. Based on these 5 factors, 3 groups (3-year GRFS: 64.9% in low risk, 33.6% in intermediate risk, and 6.6% in high risk; P.001) were identified. Fixed factor-adjusted GRFS in patients receiving reduced-intensity conditioning (RIC) plus high-dose ATG (≥7.5 mg/kg) was superior (P.001) to those receiving MAC and/or low-dose ATG. Favorable influences of RIC plus ATG ≥ 7.5 mg/kg were evident in the low-risk group defined by fixed factors (3-year GRFS, 38.9% versus 4.4%; P.001) but were not evident in the high-risk group (3-year GRFS, .0% versus 5.3%; P = .678). Conclusively, this study suggests that risk-adapted selection of conditioning intensity and ATG could improve qualified HSCT outcomes.

Background Numerous studies have focused on solvent extracts from locust trees (Gleditsia spp.), which contain diverse bioactive components including saponins, flavonoids, and alkaloids. However, because of the undefined nature of such phytochemicals, their clinical application as chemotherapeutic agents has often been limited. Purpose This study aimed to evaluate the anti-oncogenic activity of triacanthine, an alkaloid obtained from Gleditsia triacanthos L. Study Design The anti-oncogenicity of triacanthine in vitro was evaluated via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, cell-counting kit-8 assay (CCK-8 assay), flow cytometry, imunoblot, migration and invasion assays, zymography, and electrophoretic mobility shift assay in the human bladder carcinoma cell line EJ. The in vivo efficacy of triacanthine was evaluated via oral administration to EJ-xenografted BALB/c nude mice. To identify the side effects of triacanthine, cisplatin was also administered and an acute toxicity test was performed. Results Triacanthine significantly inhibited EJ cell proliferation (IC50 600 µM). Flow cytometry analysis revealed that cells were arrested in the G1 phase, and apoptotic cells accumulated in sub-G1 phase in a dose-dependent manner. Triacanthine inhibited the G1–S transition by deterring complex formation between cyclin-dependent kinases and cyclins, thereby up-regulating cell cycle inhibitors p21WAF1 and p27KIP1. In addition, triacanthine induced a caspase-dependent extrinsic pathway of apoptosis and autophagy. Early responsive kinases, extracellular signal-regulated kinase (ERK) and Janus kinase (JNK) were up-regulated by triacanthine. Triacanthine-mediated inhibition of the migratory and invasive potential of EJ cells was attributed to reduction of matrix metalloproteinase (MMP)-9 due to suppression of binding activities of the transcription factors activator protein (AP)-1, specificity protein (Sp)-1, and nuclear factor (NF)-κB. In an in vivo study, triacanthine significantly limited growth of xenografted tumors. Interestingly, while cisplatin resulted in significant weight loss after a 5-mg/kg dose, triacanthine did not cause weight loss, behavioral abnormalities, altered biochemical parameters, or tissue staining. A single oral dose acute-toxicity test (triacanthine 2,000 mg/kg) produced no adverse cytotoxic effects via blood biochemical tests and tissue-organ staining. Conclusion To our knowledge, this is the first systematic evaluation of the anti-oncogenic activity of triacanthine. Therefore, we believe that our findings may guide the development of novel chemotherapeutic agents for bladder cancers.

We investigate the electrical characteristics of Schottky contacts for an Au/hydride vapor phase epitaxy (HVPE) a-plane GaN template grown via in situ GaN nanodot formation. Although the Schottky diodes present excellent rectifying characteristics, their Schottky barrier height and ideality factor are highly dependent upon temperature variation. The relationship between the barrier height, ideality factor, and conventional Richardson plot reveals that the Schottky diodes exhibit an inhomogeneous barrier height, attributed to the interface states between the metal and a-plane GaN film and to point defects within the a-plane GaN layers grown via in situ nanodot formation. Also, we confirm that the current transport mechanism of HVPE a-plane GaN Schottky diodes grown via in situ nanodot formation prefers a thermionic field emission model rather than a thermionic emission (TE) one, implying that Poole&ndash, Frenkel emission dominates the conduction mechanism over the entire range of measured temperatures. The deep-level transient spectroscopy (DLTS) results prove the presence of noninteracting point-defect-assisted tunneling, which plays an important role in the transport mechanism. These electrical characteristics indicate that this method possesses a great throughput advantage for various applications, compared with Schottky contact to a-plane GaN grown using other methods. We expect that HVPE a-plane GaN Schottky diodes supported by in situ nanodot formation will open further opportunities for the development of nonpolar GaN-based high-performance devices.

Hemophagocytic lymphohistiocytosis is an overwhelming systemic inflammatory process that is life-threatening if not treated appropriately. We analyzed prognostic factors in patients with secondary hemophagocytic lymphohistiocytosis excluding malignancy. In this retrospective study, we analyzed 126 adult cases between 2001 and 2017. Treatment was based on dexamethasone with or without etoposide and cyclosporine. Patients who achieved a complete response by 4 weeks were defined as early stable responders, those who failed to achieve a complete response but showed continuous improvement until 8 weeks were defined as late responders, and those whose conditions waxed and waned until 8 weeks were defined as unstable responders. Patients with hemophagocytic lymphohistiocytosis caused by Epstein-Barr virus had a worse 5-year overall survival compared to those whose disease was secondary to autoimmune disease, other infections, or unknown causes (25.1% versus 82.4%, 78.7% and 55.5%, respectively; P

We report on the defect states incorporated in a-plane GaN crystals grown on r-plane sapphire substrates by hydride vapor phase epitaxy (HVPE), using deep level transient spectroscopy (DLTS). Two defect states were observed at 0.2 eV and 0.55 eV below the conduction band minimum with defect densities of 5 × 1012/cm3 and 4.7 × 1013/cm3, respectively. The size of capture cross section, non-linear relation of trap densities from the depth profile, filling pulse width, and PL measurements indicated that the electronic deep trap levels in a-plane GaN on r-plane sapphire by HVPE originated from non-interacting point defects such as NGa, complex defects involving Si, O, or C, and VGa-related centres. Even though the a-plane GaN templates were grown by HVPE with high growth rates, the electronic deep trap characteristics are comparable to those of a-plane GaN layers of high crystal quality grown by MOCVD. This study prove that the growth of a-plane GaN templates on r-plane sapphire by HVPE is a promising method to obtain a-plane GaN layers efficiently and economically without the degradation of electrical characteristics.

One of the essential concerns in CO2 storage is the risk of CO2 leakage from the storage site. The characterization of the properties of the caprock and aquifers influencing the leakage of CO2 from storage sites into overlying formations is of significant importance. Considering solubility trapping and residual gas trapping mechanisms, numerical simulations were conducted to evaluate and understand the effects of the properties of the storage formations associated with leakage through the caprock. Based on the results, a sensitivity analysis was carried out under a wide range of variation in these properties. The formation properties included permeability and porosity of caprock and aquifer, formation dip, vertical-to-horizontal permeability ratio, salinity, and temperature. According to the simulation results, the amount of leakage increased with an increase in the permeability of the caprock and aquifer, the vertical-to-horizontal permeability ratio, and the temperature. The amount of leakage de...

We report that the addition of 1–4.5 wt% Al to Mg–5Sn–1Zn alloy results in grain refinement and a significant decrease in yield asymmetry in the extruded condition. The Mg–5Sn–1Zn alloy with 4.5 wt% Al showed nearly symmetric yielding behavior at room temperature, exhibiting a compressive-to-tensile yield strength ratio of 0.99. The reduced yield asymmetry is discussed in terms of microstructure and texture.

In this study, we show that reduction of glucose concentration increases TR4 expression in 3T3-L1 cells via stimulation of the GSK-3β-CREB pathway. While GSK-3β and CREB increased TR4 expression in 3T3-L1 cells, inhibition of CREB expression or activity resulted in loss of GSK-3β-mediated enhancement of TR4 expression. In addition, CREB enhanced murine TR4 promoter activity via direct binding to a cAMP response element located in the promoter, and this CREB effect was further strengthened by GSK-3β. Moreover, silencing of TR4 expression by a gene-specific microRNA inhibited CREB-induced lipid accumulation in 3T3-L1 adipocytes, suggesting that TR4 could be a key mediator of CREB-induced lipogenesis.

고속으로 주행하는 열차의 정확한 위치를 차상에서 검지하기 위해서는 지상에 설치된 트랜스폰더 태그로부터 위치정보를 정확하고 신속하게 수신하는 것이 필수적이다. 본 논문에서는 고속용으로 개발중인 트랜스폰더시스템의 텔레그램 적용을 위해 텔레그램 복호화(decoding) 속도를 개선하기 위한 병렬 디스크램블링 기법을 제안하였다. 텔레그램은 유저 데이터를 스크램블링(scrambling)하는 부호화(encoding) 과정을 거쳐 트랜스폰더 태그에 저장되므로, 트랜스폰더 리더가 유저 데이터를 복호화(decoding)하는 과정에서 디스크램블링(descrambling)이 필수적이다. 본 논문에서는 디스크램블링 시프트 레지스터 회로 구조 분석을 통해 텔레그램의 병렬 디스크램블링 기법을 제안하고, 제안된 기법을 사용할 경우 기존 방식에 비해 필요 클락 수를 현저히 낮출 수 있음을 보였다.

The tensile properties and load relaxation behavior of extruded Mg–8Sn–3Al–1Zn alloy at 250 °C were investigated. Superplasticity was observed in the alloy, which exhibited tensile elongations of 450–1050% at strain rates in the range of 5×10 -4 –5×10 −3 s −1 . Load relaxation results at 250 °C indicated that grain boundary sliding is responsible for the superplastic properties of the alloy, even though it does not act as a primarily operating deformation mechanism.

Background/aims The diagnosis of chronic thromboembolic pulmonary hypertension (CTEPH) is difficult for numerous reasons and is related with a poor prognosis. In Korea, the incidence of CTEPH and its clinical features are unknown. Thus, in this study, we evaluated the clinical characteristics and outcomes of CTEPH in a Korean cohort. Methods This study included South Korean patients diagnosed with CTEPH between September 2008 and October 2011. Baseline characteristics, treatments and outcomes were analyzed. Results A total of 134 patients were included in this study with 76 females (56.7%). Their median age was 58.3 ± 15.9 years and dyspnea (112 patients, 83.5%) was the most common presenting symptom. Sixty-three patients (47%) had a history of acute pulmonary embolism or deep vein thrombosis, and six (4.5%) had pulmonary tuberculosis. In total, 28 patients (21%) underwent pulmonary thromboendarterectomy (PTE), and 99 patients had medical therapy. During the study period, 18 patients (13.4%) died. In a multivariate analysis, higher hemoglobin (relative risk [RR], 1.516; 95% confidence interval [CI], 1.053 to 2.184; p = 0.025) and lower total cholesterol levels (RR, 0.982; 95% CI, 0.965 to 0.999; p = 0.037) were associated with increased mortality. Conclusions This was the first national cohort study of Korean patients with CTEPH. Accurate diagnosis, characterization and distributions of CTEPH are imperative for prompt treatment in patients, particularly those undergoing PTE.

The influence of rolling reduction on the microstructural variations in Ti-containing tool steel was investigated. The microstructures, including the prior-austenite grain structure and primary/secondary carbides, were characterized using optical and electron microscopy; the carbides were quantitatively analyzed by small-angle neutron scattering data collected from macro-samples. In parallel with refining the primary carbides, increases in the degree of rolling reduction significantly changes the precipitation kinetics of the secondary MC and M23C6 (M = metallic element) carbides, and thus their mechanical properties, especially the hardness to toughness balance throughout the aging. The improvement of this balance is attributed to the refinement of the prior-austenite grain structure, as well as the retardation of M23C6 precipitation. The reaction kinetics of the precipitation reactions were analyzed by the reduced heat of reaction observed in a calorimetry experiment.

A touch system sensing pen-pressure of the proposed electrically coupled resonance (ECR) pen is implemented, which can replace costly digitizer system containing electro magnetic resonance (EMR) and capacitive touch system. The proposed system detects the location of the ECR pen and finger using proposed position sensor, and senses pen-pressure of ECR pen using proposed pen-pressure sensor. For the position sensor, to detect even small variation of the mutual capacitance on touch screen panel (TSP) of the pen, a simultaneous driving scheme is proposed with modified Hadamard matrix, resulting in highly increased dynamic range and SNR. In the proposed pen-pressure sensor, the resonant frequency of the ECR pen is measured by a frequency to voltage converter based sensor. The measured SNR for the pen position is 49 dB with 1 mm ${\mmb\varphi}$ metal pillar, and 6.5-bit resolution is achieved for pen-pressure sensor in $6\sigma$ criteria.

In D7 tool steel, which contains high levels of primary carbides, the influence of carbide modification by Ti addition was quantitatively analyzed. Considering the Griffith-Irwin energy criterion for crack growth, the impact energy was evaluated by substituting a microscopic factor of the normalized number density of carbides cracked during hardness indentation tests for the crack length. The impact energy was enhanced with Ti addition because Ti reduced and refined the primary M7C3 carbide phase of elongated morphology, reducing the probability of crack generation.

Pentane-1,2-dicarboxylic acid functionalized spherical MCM-41 nanoparticles (DA-MCM-41) were prepared by a two step modification process started from the hydrothermal synthesis of mesoporous spherical silica particles. 3-(triethoxysilyl)propylsuccinic anhydride (TEPSA) was immobilized over spherical MCM-41 after the surfactant removal by calcination and the proceeding hydrolysis shaped the DA-MCM-41. The synthesized materials were well characterized by various spectroscopic analyses. As a potential application, DA-MCM-41 was effectively utilized for the removal of Fe 3+ from aqueous solutions containing various metal ions. The adsorption using DA-MCM-41 was found to have 100% mole and weight selectivities for Fe 3+ from aqueous solution containing Cr 3+ , Mn 2+ , Fe 3+ , Co 2+ , Ni 2+ , Cu 2+ , Zn 2+ , Cd 2+ and Pb 2+ ions at pH 2, 3, 4 and 5. The material also exhibited 100% mole and weight selectivities for Fe 3+ from metal ion mixture containing Li + , Na + , Ca 2+ and Mg 2+ along with the previously mentioned heavy metals at pH 2 and 3. Interestingly, at pH 4, 5 and 6 the alkali and alkaline earth metals adversely affected the mole and weight selectivities of Fe 3+ ions. The reusability test revealed that the DA-MCM-41 can recycle for at least five consecutive cycles without losing the adsorption ability considerably. Also the ligand has excellent adsorption and binding abilities towards Fe 3+ from the mixture.