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One puzzle in loanword adaptation involves a situation in which a foreign sound structure is modified even when the original form would be phonotactically legal in the borrowing language. An example of this apparently unnecessary repair is the tendency to insert a vowel after a word-final stop in English borrowed words into Korean since Korean native words can end in a stop. This study investigates the effects of different linguistic factors, i.e., release and voicing of the English final stop and tenseness of pre-stop vowel, on the likelihood of vowel insertion to determine whether this unmotivated vowel insertion derives from the misperception of English words. The current study separates out the effects of these linguistic factors in a perception experiment designed to help in testing the hypotheses of the adaptation-in-perception approach. In the categorization task, Korean listeners heard English nonwords ending in a stop or in a stop-vowel sequence and categorized each word as consonant-final or vowel-final. Although the present results concerning the main effects of all factors are compatible with the adaptation-in-perception approach, the interaction effects between stop voicing and vowel tenseness suggest that alongside the phonological factors that were considered in this study, other possible factors may play a role in loanword adaptation, e.g., maintaining perceptual similarity in production, stop place, word size, and final syllable containing stress. This indicates that unnecessary vowel insertion is not a straightforward outcome that happens in adaptation but an intricate linguistic phenomenon that involves the complex interaction of perception, production and several other factors.

A narrow process window for the fabrication of p-type semiconductors is one of the major challenges in implementing tin oxide (SnO x ) in thin film transistor applications. The SnO x lattice was doped with Al to widen the process window and enhance the p-type channel thin film transistor performance with co-sputtering process. A change in the growth orientation direction with the presence of Al in SnO x thin films was observed in the grazing-incidence X-ray diffraction data. The changes in the oxidation states of Sn ions were determines by X-ray photoelectron spectroscopy. With increasing Al concentration, the ratio of Sn 4 + in the Sn peaks decreases indicating that the SnO x film has improved p-type properties. These changes led to an improvement of the electrical properties such as output characteristic, field effect mobility, subthreshold swing, and positive shift of threshold voltage.

A growing number of studies have been carried out to understand learning and teaching activities in online learning environments (OLEs) and to design effective OLEs for meaningful learning in higher education. Although there were a small number of studies to provide research trends in educational technology in regards to research topics, methods, and researchers, more research is necessary to help educators to understand new trends and issues of OLEs in higher education. This study intends to provide an overview of practical and theoretical issues pertaining to OLEs by analyzing literature recently published in peer-reviewed journals. The present study qualitatively analyzed research questions and purposes to identify themes of OLEs in higher education. The OLE research topics were grouped into three major themes: (1) participants, (2) micro-level environments, and (3) macro-level environments. The findings are followed by discussion of an ecological approach as a new theoretical framework to guide future OLE research and practice.

Methionine aminopeptidases (MetAPs), ubiquitous enzymes that play an important role in nascent protein maturation, have been recognized as attractive targets for the development of drugs against pathogenic protozoa including Plasmodium spp. Here, we characterized partial biochemical properties of a type I MetAP of Plasmodium vivax (PvMetAP1). PvMetAP1 had the typical amino acid residues essential for metal binding and substrate binding sites, which are well conserved in the type I MetAP family enzymes. Recombinant PvMetAP1 showed activity in a broad range of neutral pHs, with optimum activity at pH 7.5. PvMetAP1 was stable under neutral and alkaline pHs, but was relatively unstable under acidic conditions. PvMetAP1 activity was highly increased in the presence of Mn(2+), and was effectively inhibited by a metal chelator, EDTA. Fumagillin and aminopeptidase inhibitors, amastatin and bestatin, also showed an inhibitory effect on PvMetAP1. The enzyme had a highly specific hydrolytic activity for N-terminal methionine. These results collectively suggest that PvMetAP1 belongs to the family of type I MetAPs and may play a pivotal role for the maintenance of P. vivax physiology by mediating protein maturation and processing of the parasite.

Melittin is a cationic, hemolytic peptide that is the main toxic component in the venom of the honey bee (Apis mellifera). It has been used in treatment of various chronic inflammatory diseases. However, the cellular mechanism and the anti-apoptotic effect of melittin in Propionibactierium acnes (P. acnes)-induced THP-1 cells have not been explored. In the present study, we investigated the anti-inflammatory and anti-apoptotic mechanism by examining the effect of melittin on P. acnes-induced THP-1 monocytic cells. THP-1 monocytic cells were stimulated by heat-killed P. acnes in the presence of melittin. The expression levels of pro-inflammatory cytokines, NF-κB signaling, caspase family, and PARP signaling were measured by ELISA or Western blot analysis. The number of apoptotic cells and changes of cell morphology were examined using fluorescence microscopy and flow cytometry. Heat-killed P. acnes increased the secretion of pro-inflammatory cytokines and cleavage of caspase-3 and -8 in heat-killed P. acnes-induced THP-1 cells. However, treatment with melittin inhibited the pro-inflammatory cytokines and cleavage of the caspase-3 and -8. Moreover, the cleaved PARP appeared after 8h of heat-killed P. acnes treatment and its cleavage was reduced by melittin treatment. These results demonstrate that 1.0×10(7) CFU/ml of heat-killed P. acnes induces THP-1 cell apoptosis and secretion of inflammatory cytokines. Also, administration of melittin significantly decreases the expression of various inflammatory cytokines in heat-killed P. acnes-treated THP-1 monocytic cells. In particular, melittin exerts anti-apoptotic effects against 1.0×10(7) CFU/ml of heat-killed P. acnes injury to THP-1 cells.

Apamin is an integral part of bee venom, as a peptide component. It has long been known as a highly selective block Ca2+-activated K+ (SK) channels. However, the cellular mechanism and anti-fibrotic effect of apamin in TGF-β1-induced hepatocytes have not been explored. In the present study, we investigated the anti-fibrosis or anti-EMT mechanism by examining the effect of apamin on TGF-β1-induced hepatocytes. AML12 cells were seeded at ∼60% confluence in complete growth medium. Twenty-four hours later, the cells were changed to serum free medium containing the indicated concentrations of apamin. After 30 min, the cells were treated with 2 ng/ml of TGF-β1 and co-cultured for 48 h. Also, we investigated the effects of apamin on the CCl4-induced liver fibrosis animal model. Treatment of AML12 cells with 2 ng/ml of TGF-β1 resulted in loss of E-cadherin protein at the cell–cell junctions and concomitant increased expression of vimentin. In addition, phosphorylation levels of ERK1/2, Akt, Smad2/3 and Smad4 were increased by TGF-β1 stimulation. However, cells treated concurrently with TGF-β1 and apamin retained high levels of localized expression of E-cadherin and showed no increase in vimentin. Specifically, treatment with 2 μg/ml of apamin almost completely blocked the phosphorylation of ERK1/2, Akt, Smad2/3 and Smad4 in AML12 cells. In addition, apamin exhibited prevention of pathological changes in the CCl4-injected animal models. These results demonstrate the potential of apamin for the prevention of EMT progression induced by TGF-β1 in vitro and CCl4-injected in vivo.

Clear cell renal cell carcinoma (ccRCC), which accounts for the majority of kidney cancer, is known to accumulate excess cholesterol. However, the mechanism and functional significance of the lipid accumulation for development of the cancer remains obscure. In this study, we analyzed 42 primary ccRCC samples, and determined that cholesterol levels of ~ 70% of the tumors were at least two-fold higher than that of benign kidney tissues. Compared to tumors without cholesterol accumulation, those containing excess cholesterol expressed higher levels of scavenger receptor BI (SR-B1), a receptor for uptake of HDL-associated cholesterol, but not genes involved in cholesterol synthesis and uptake of LDL-associated cholesterol. To further determine the roles of sterol accumulation for cancer development, we implanted ccRCC from patients into mouse kidneys using a mouse ccRCC xenograft model. Feeding mice with probucol, a compound lowing HDL-cholesterol, markedly reduced levels of cholesterol in tumors containing excess cholesterol. This treatment, however, did not affect growth of these tumors. Our study suggests that cholesterol overaccumulation in ccRCC is the consequence of increased uptake of HDL-cholesterol as a result of SR-B1 overexpression, but the lipid accumulation by itself may not play a significant role in progression of the cancer.

Theileria equi is a tick-transmitted intraerythrocytic protozoan parasite in equids. Equine merozoite antigen (EMA)-1 and EMA-2 of T. equi have been identified as immunodominant proteins co-expressed on the surface of extra-erythrocytic merozoites. Additionally, only the EMA-2 is shed into the cytoplasm of infected erythrocyte or inside the erythrocytic membrane during their early developmental stage. In this study, we initially performed West-Western blot analysis on Triton X-100-insoluble erythrocytic skeleton collected from a healthy horse, using a glutathione S-transferase (GST)-tagged recombinant EMA-1t or EMA-2t of T. equi. The results indicated positive interactions of actin and band 4.1 molecules in the equine erythrocytic skeleton only with the recombinant EMA-2t. Subsequently, we carried out GST pull-down assay using the recombinant antigens (as above) against solubilized lysate of equine erythrocytic skeleton, and confirmed the co-precipitation of actin molecule with EMA-2t, but not with the EMA-1t. The interaction of EMA-2 with host erythrocytic actin indicated its role in the pathobiology of T. equi infection within host erythrocytes.

Proximal epithelioid sarcoma (PES) is an extremely uncommon neoplasm of the vulva with an aggressive behavior. Recently, these authors experienced a case of proximal-type ES in a 41-year-old woman who was admitted for a rapidly growing mass in the right mons pubis. An about-1-cm-sized mass was initially noticed one and a half years earlier. The excised mass, however, was 8 cm in greatest dimension and was relatively well circumscribed. The cut surface was trabeculated, with multifocal hemorrhages and necroses. Microscopically, the tumor consisted of epithelioid rhabdoid cells with vesicular nuclei, large prominent nucleoli, and cytoplasmic eosinophilic globules comparted by thin, fibrous septae. The main differential diagnoses included PES, other sarcomas with epithelioid cells, malignant melanoma, and sarcomatoid carcinoma. The tumor cells were diffusely positive for vimentin and EMA; focally positive for cytokeratin; and negative for CK5/6, CD34, S-100 protein, desmin, and myogenin. INI1 (hSNF5/SMARCB1, a member of the SW1/SNF chromatin remodeling complex located on chromosome 22q11.2) staining clearly showed loss of expression in the tumor cells. Recent studies reported that some ESs also showed INI1 inactivation, as characteristically seen in malignant rhabdoid tumors of infancy. Reported herein is the diagnostic utility of INI-1 on PES and the possible relationship between PES and malignant rhabdoid tumor of the soft tissue, besides a collective review of the reported cases of PES of the vulva and of the current case.

Small intestinal adenocarcinoma is a rare malignant neoplasm, and its clinicopathologic characteristics have not been well elucidated. A total of 197 small intestinal adenocarcinoma cases were collected from 22 institutions in South Korea and were evaluated for clinicopathologic factors that affect the prognosis of small intestinal adenocarcinoma patients using univariate and multivariate analyses. The mean patient age was 59 years, and the male-to-female ratio was 1.7:1. Tumors were located in the duodenum of 108 cases (55%), the jejunum in 59 (30%), and the ileum in 30 (15%). Predisposing conditions were observed in 23 cases (12%), including 17 cases with sporadic adenomas, 3 with Peutz-Jeghers syndrome, 2 with Meckel diverticulum, and 1 with Crohn disease. Synchronous or metachronous malignant tumors were identified in 31 cases (16%), including 13 colorectal and 10 stomach cancers. About 90% of tumors were classified as either pT3 (63 cases) or pT4 (112 cases). The median survival time for all small intestinal adenocarcinoma patients was 39.7 months. Compared with small intestinal adenocarcinomas without accompanying sporadic adenomas, small intestinal adenocarcinomas with accompanying adenomas were more well differentiated (P < .0001), with a more polypoid growth pattern (P < .0001), a lower pT classification (P < .0001), less perineural invasion (P = .01), and less lymphatic invasion (P = .03). Small intestinal adenocarcinoma patients with associated sporadic adenomas (77%) had a significantly better 5-year survival rate than those without sporadic adenomas (38%, P = .02). By univariate analysis, small intestinal adenocarcinoma patients had significantly different survival based on pT classification (P = .003), lymph node metastasis (P < .0001), distal location (jejunal and ileal carcinomas) (P = .003), retroperitoneal tumor seeding (P < .0001), vascular invasion (P = .007), lymphatic invasion (P = .001), peritumoral dysplasia (P = .004), and radiation therapy (P = .006). By multivariate analysis, lymph node metastasis (P = .01) and distal location (P = .003) were independent predictors of a worse prognosis. In conclusion, (1) small intestinal adenocarcinomas are diagnosed at an advanced disease stage; therefore, the development of strategies for detection at an earlier stage is needed. (2) Small intestinal adenocarcinoma patients with an adenomatous component had a better survival than those without an adenomatous component. (3) Lymph node metastasis and distal location (jejunum and ileum) of tumor are the most important independent prognostic factors.

Malaria is endemic or hypoendemic in Myanmar and the country still contributes to the high level of malaria deaths in South-East Asia. Although information on the nature and extent of population diversity within malaria parasites in the country is essential not only for understanding the epidemic situation but also to establish a proper control strategy, very little data is currently available on the extent of genetic polymorphisms of the malaria parasites in Myanmar. In this study, we analyzed the genetic polymorphism and natural selection at domain I of the apical membrane antigen-1 (AMA-1) among Plasmodium vivax Myanmar isolates. A total of 34 distinguishable haplotypes were identified among the 76 isolates sequenced. Comparison with the previously available PvAMA-1 sequences in the GenBank database revealed that 21 of them were new haplotypes that have never been reported till date. The difference between the rate of nonsynonymous (dN) and synonymous (dS) mutations was positive (dN-dS, 0.013+/-0.005), suggesting the domain I is under positive natural selection. The Tajima's D statistics was found to be -0.74652, suggesting that the gene has evolved under population size expansion and/or positive selection. The minimum recombination events were also high, indicating that recombination may occur within the domain I resulting in allelic diversity of PvAMA-1. Our results collectively suggest that PvAMA-1 displays high genetic polymorphism among Myanmar P. vivax isolates with highly diversifying selection at domain I. These results have significant implications in understanding the nature of P. vivax population circulating in Myanmar as well as providing useful information for malaria vaccine development based on this antigen.

Loop-mediated isothermal amplification (LAMP) is a novel technique that rapidly amplifies target DNA in isothermal conditions. In a previous study, the sensitivities and specificities of LAMP, microscopy, and nested PCR were compared in the context of rapid malaria detection. In the present study, LAMP detected vivax malaria parasites in 115 of 117 microscopically positive samples (sensitivity, 98.3%; 95% CI, 97.4–100%), which agreed well with the nested PCR results (sensitivity, 99.1%; 95% CI: 96.0–100%). No positive cases of malaria were detected by LAMP or nested PCR in 50 consecutive feverish patients other than malaria from malaria endemic areas. LAMP performed on DNA extracted from heat-treated blood had a sensitivity of 93.3% (28/30, 95% CI: 84.4–100%) and specificity of 100% (30/30, 95% CI: 100%). The present study shows that LAMP based assays have high sensitivity, specificity, and amplification efficiencies for Plasmodium vivax detection. The authors recommend that LAMP can be considered as a rapid nucleic acid amplification assay for the molecular diagnosis of P. vivax in both clinical laboratories and malaria clinics in areas where vivax malaria is endemic.

Malaria is one of the most serious problems threatening human health in Myanmar. Although the morbidity and mortality rates due to malaria have been gradually declining, Myanmar still contributes to a large proportion of malarial death in the South-East Asia region. However, little is known about the nature and extent of genetic diversity of the malarial parasites circulating in Myanmar. In this study, we investigated the overall infection status of Plasmodium and the population diversity of Plasmodium vivax by analyzing three genetic markers, circumsporozoite protein (CSP), merozoite surface protein-1 (MSP-1), and merozoite surface protein-3 (MSP-3α), of P. vivax field isolates collected from infected individuals. In 349 blood samples collected from the individuals who exhibited clinical symptoms associated with malaria, 63.0% showed a positive result for malaria (220/349). P. vivax was detected in 58.2% (128/220) and Plasmodium falciparum was detected in 29.1% (64/220). Mixed infections with both parasites were detected in 12.7% (28/220). The 116 blood samples in which single infection of P. vivax was confirmed were selected and subjected to further genetic analysis. Genotyping of the CSP gene of P. vivax showed that VK210 type (98.3%, 114/116) is predominant in Myanmar, but a significant level of mixed infections of VK210 and VK247 types (24.1%, 28/116) was also identified. Sequence analyses of MSP-1 and MSP-3α genes revealed a large number of distinguishable alleles: 12 for MSP-1 and 25 for MSP-3α . These results collectively suggest that the P. vivax population in Myanmar is highly diverse and multiple clonal infections are prevalent in the country.

Posttransplantation lymphoproliferative disorder (PTLD) of T-cell origin has been rarely described in chronically immunosuppressed allograft recipients. We report a case of renal PTLD of a T lineage that occurred shortly after transplantation under a triple-immunosuppressive regimen. Renal graft biopsy performed 58 days posttransplantation showed extensive interstitial infiltrates of polymorphic lymphoid cells, which expressed the UCHL-1 and CD3 markers for T-cell lineage. The clonal nature of the T cells in renal tissue was identified by showing rearrangement of the T-cell receptor gamma chain genes using a polymerase chain reaction (PCR). DNA extracted from the graft biopsy specimen did not show the sequences of human T-cell leukemia virus type 1 (HTLV-1) by PCR. Signals for Epstein-Barr virus (EBV) infection in renal tissue were not shown by in situ hybridization. After the reduction of immunosuppressive therapy, regression of PTLD lesion and development of rejection were shown in the second graft biopsy and graftectomy specimen. The extreme rarity of rapidly developing T-cell PTLD in a renal allograft prompted us to write this report.