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Stress management is necessary for vertebrate survival. Chronic stress drives depression by excitation of the lateral habenula (LHb), which silences dopaminergic neurons in the ventral tegmental area (VTA) via GABAergic neuronal projection from the rostromedial tegmental nucleus (RMTg). However, the effect of acute stress on this LHb-RMTg-VTA pathway is not clearly understood. Here, we used fluorescent in situ hybridisation and in vivo electrophysiology in mice to show that LHb aromatic l-amino acid decarboxylase-expressing neurons (D-neurons) are activated by acute stressors and suppress RMTg GABAergic neurons via trace aminergic signalling, thus activating VTA dopaminergic neurons. We show that the LHb regulates RMTg GABAergic neurons biphasically under acute stress. This study, carried out on male mice, has elucidated a molecular mechanism in the efferent LHb-RMTg-VTA pathway whereby trace aminergic signalling enables the brain to manage acute stress by preventing the hypoactivity of VTA dopaminergic neurons.

Recent observations showed that boreal winter exhibits significant cooling events in the Eurasian and North American continents despite the global warming trend. To better understand the boreal winter surface air temperature (SAT) variability and its physical characteristics, we investigated the three distinct Empirical Orthogonal Function (EOF) modes of the extratropical 2-m air temperature (T2m) variation and found that each mode can be related to the well-known physical processes: The first mode is characterized by the coherent change of wintertime SAT anomalies over northern Eurasia and central-eastern North America and it is found that snow cover variation in the Eurasian region can modulate Arctic Oscillation (AO) circulation through the troposphere–stratosphere interaction, which can affect wintertime SAT in the two continents. The second leading mode shows warm anomalies over the North Pacific especially around the Bering Strait and cold anomalies over most of Canada and the central part of North America. Associated with this mode, La Nina-like sea surface temperature (SST) anomaly can modulate the North American SAT variability through the generation of the tropospheric Pacific–North American (PNA) teleconnection pattern. The third mode represents warm anomalies over the Barents and Kara (B–K) seas and cold anomalies over East Asia. Sea ice loss over the B–K sea is analyzed to be closely related to the SAT variability over the East Asian region.

A modified endoscopic mucosal resection (EMR) technique, Tip-in EMR, was recently introduced to enhance the complete resection of colorectal neoplasia (CRN). We aimed to evaluate the feasibility of Tip-in EMR for flat CRNs. From January to September 2018, conventional or Tip-in EMR was consecutively performed for 112 flat CRNs ≥ 10 mm in diameter. Tip-in EMR was performed when en bloc snaring was impossible with conventional EMR or when a lesion was inadequately lifted owing to a previous forceps biopsy. We retrospectively collected the clinical, procedural, and histologic data of the conventional and Tip-in EMR groups and compared the en bloc resection rate, complete resection rate, and complications between the two groups. Among 112 flat CRNs of 80 patients, conventional EMR and Tip-in EMR were performed for 74 and 38 lesions, respectively. The median lesion size was 12 (10–27) mm. Tip-in EMR was superior to conventional EMR in terms of en bloc resection (94.7% vs. 77.0%, p = 0.018) and histologic complete resection (76.3% vs. 54.1%, p = 0.022). There was no difference in postprocedural bleeding between the two groups; however, overall adverse events, including bleeding and postpolypectomy electrocoagulation syndrome, were more frequent in the Tip-in EMR group. Tip-in EMR is a feasible technique for flat colorectal lesions ≥ 10 mm and is superior to conventional EMR with respect to en bloc and complete resection rates. The safety profiles of Tip-in EMR and conventional EMR should be compared via large-scale prospective studies.

This paper deals with a novel clutch mechanism for transmission applications, which aims at easy application of the transmission as the micro-electric vehicle models expand in variety. The new mechanism actuated by the torque and rotational inertia of the traction motor instead of the conventional hydraulic or electronic actuator and features a simple structure compared to the conventional mechanism. The operating principle, structure and mathematical modeling of the new clutch mechanism are presented, and verification of mathematical modeling was done through comparison of experimrntal and analytical results. To investigate the automotive suitability of the new clutch mechanism, the shift characteristics are analyzed by longitudinal directional vehicle dynamic model applying new clutch mechanism. As a result of the analysis, it was confirmed that the shift shock absorbing ability and required time for shifting are applicable to the vehicle transmission.

Recently, as a new precast concrete (PC) construction method for increasing economy and constructability, the PC double-beam system has been developed for factories or logistic centers, where construction duration is particularly important. In this study, half-scaled PC double beam–column connection was tested under gravity loading and cyclic lateral loading. The major test parameters included the use of the spliced PC column and the addition of reinforcement at the beam–column joint. In the gravity loading test, the flexural behavior of the PC double beam was investigated. The test results showed satisfactory flexural capacity at the PC double-beam section, validating the composite action between the PC and RC members. In the cyclic lateral loading test, the seismic performance of the PC double beam–column connection was investigated. Based on the test results, the failure mode, load-carrying capacity, deformation capacity, energy dissipation capacity, secant stiffness, and shear strength of the PC double-beam system were evaluated and compared with those of a conventional RC double beam–column connection. According to the test results, the structural performance of the PC double beam–column connection was comparable to that of the RC double beam–column connection and satisfied the acceptance criteria of moment frame in the ACI 374.1-05 provision.

An ensemble statistical forecast scheme with a one-month lead is developed to predict year-to-year variations of Changma rainfall over the Korean peninsula. Spring sea surface temperature (SST) anomalies over the North Atlantic, the North Pacific and the tropical Pacific Ocean have been proposed as useful predictors in a previous study. Through a forward-stepwise regression method, four additional springtime predictors are selected: the northern Indian Ocean (NIO) SST, the North Atlantic SST change (NAC), the snow cover anomaly over the Eurasian continent (EUSC), and the western North Pacific outgoing longwave radiation anomaly (WNP (OLR)). Using these, three new prediction models are developed. A simple arithmetic ensemble mean produces much improved forecast skills compared to the original prediction model of Lee and Seo (2013). Skill scores measured by temporal correlation and MSSS (mean square error skill score) are improved by about 9% and 17%, respectively. The GMSS (Gerrity skill score) and hit rate based on a tercile prediction validation scheme are also enhanced by about 19% and 13%, respectively. The reversed NIO, reversed WNP (OLR), and reversed NAC are all related to the enhancement of a cyclonic circulation anomaly to the south or southwest of the Korean peninsula, which induces southeasterly moisture flux into the peninsula and increasing Changma precipitation. The EUSC predictor induces an enhancement of the Okhotsk Sea high downstream and thus strengthening of Changma front.

A deficiency of α-galactosidase A causes Fabry disease (FD) by disrupting lipid metabolism, especially trihexosylceramide (THC). Enzyme replacement therapy (ERT) is clinically offered to FD patients in an attempt to lower the accumulated lipids. Studies on specific types of lipids that are directly or indirectly altered by FD are very scarce, even though they are crucial in understanding the biological process linked to the pathogenesis of FD. We performed a comprehensive lipid profiling of plasma and urinary lipids from FD patients with nanoflow liquid chromatography electrospray-ionization tandem mass spectrometry (nLC-ESI-MS/MS) and identified 129 plasma and 111 urinary lipids. Among these, lipids that exhibited alternations (>twofold) in patients were selected as targets for selected reaction monitoring (SRM)-based high-speed quantitation using nanoflow ultra-performance LC-ESI-MS/MS (nUPLC-ESI-MS/MS) and 31 plasma and 26 urinary lipids showed significant elevation among FD patients. Higher percentages of sphingolipids (SLs; 48% for plasma and 42% for urine) were highly elevated in patients; whereas, a smaller percentage of phospholipids (PLs; 15% for plasma and 13% for urine) were significantly affected. Even though α-galactosidase A is reported to affect THC only, the results show that other classes of lipids (especially SLs) are changed as well, indicating that FD not only alters metabolism of THC but various classes of lipids too. Most lipids showing significant increases in relative amounts before ERT decreased after ERT, but overall, ERT influenced plasma lipids more than urinary lipids.

In the Original publication of the article, the grant number was incorrectly published in the acknowledge section.

Dysfunction of cholinergic signaling in the brain has long been believed to be associated with depressive disorders. However, the functional impact of habenular cholinergic signaling on the specified depressive behaviors is not well understood. Here, we demonstrated that the expression levels of cholinergic signaling genes (CHAT, VACHT, CHT, CHRNA3, CHRNB3 and CHRNB4) were down-regulated in a chronic restraint stress (CRS) rat model of depression, in which rats display depression-like behaviors such as anhedonia and mood despair. Moreover, knockdown of CHAT in the rat habenula was sufficient to evoke anhedonia-like behavior. The anhedonia-like behavior induced by CHAT knockdown was not reversed by chronic administration of the selective serotonin reuptake inhibitor fluoxetine. To determine whether habenular cholinergic signaling is associated with regulation of dopamine neurons in the ventral tegmental area (VTA) and serotonin neurons in the dorsal raphe nucleus (DRN), we used CHAT::cre transgenic mice expressing the Designer Receptors Exclusively Activated by Designer Drugs (DREADD). Pharmacogenetic activation of habenular cholinergic neurons induces the excitation of dopamine neurons in the VTA and reduces the immunoreactivity of 5-hydroxytryptamine (5-HT) in the DRN. Habenular cholinergic gene down-regulation was recapitulated in the postmortem habenula of suicide victims diagnosed with major depressive disorder (MDD).

Primary systemic anaplastic large cell lymphoma (ALCL) is divided into two entities according to the expression of anaplastic lymphoma kinase (ALK). We investigated (18)F-fluorodeoxyglucose positron emission tomography ((18)F-FDG PET) findings in primary systemic ALCL according to ALK expression.Thirty-seven patients who had baseline PET before CHOP (cyclophosphamide, doxorubicin, vincristine and prednisolone)-based chemotherapy were enrolled. Among them, patients who underwent interim and/or post-therapy PET were further investigated for the treatment response and survival analysis. Baseline PET was analyzed visually and semi-quantitatively using peakSUV, and interim and post-therapy PETs were visually analyzed.All cases were (18)F-FDG-avid on baseline PET. The peakSUV of ALK-positive ALCL (n = 16, 18.7 ± 10.5) was higher than that of ALK-negative ALCL (n = 21, 10.0 ± 4.9) (P = 0.006). In ALK-negative ALCL, complete response (CR) rate in negative-interim PET was higher than positive-interim PET (100 % vs 37.5 %, P = 0.02); however, there was no such difference in ALK-positive ALCL (100 % vs 75 %, P = 0.19). The 3-year progression-free survival (PFS) was not significantly different between ALK-positive and ALK-negative ALCL (72.7 % vs 47.6 %, P = 0.34). In ALK-negative ALCL, negative interim and post-therapy PET patients had better 3-year PFS than positive interim (83.3 % vs 25.0 %, P = 0.06) and post-therapy PET patients (70.0 % vs 20.0 %, P = 0.04). In contrast, ALK-positive ALCL had no such differences between PFS and PET results.On baseline PET, all cases showed (18)F-FDG-avidity, and ALK expression was related to higher (18)F-FDG uptake. ALK-positive patients tend to have better PFS than ALK-negative patients. Negative-interim PET was a good indicator of CR, and interim or post-therapy PET was helpful for predicting the prognosis only in the ALK-negative group.

For the conversion of β-glycosides, 3 genes (BLA_0039, BLA_0141, and BLA_0893) annotated as β-glucosidase (E.C 3.2.1.21) from the genome of Bifidobacterium lactis AD011 were cloned and expressed both in Escherichia coli DH5α and Bifidobacterium bifidum BGN4 using previously established bifidobacterial expression system under the control of 16S rRNA promoter. Deduced amino acid sequence analysis revealed that BLA_0141 is highly similar to β-d-glucosidase from Bifidobacterium breve clb and is included in glycosyl hydrolase family 1 (GHF1) while BLA_0893 belongs to glycosyl hydrolase family 3 (GHF3). Recombinant BLA_0893 showed β-glucosidase activity and converted ginsenoside Rb1 to Rd. Recombinant BLA_0141 showed broad range of activities including β-glucosidase, β-galactosidase, β-xylosidase, cellobiosidase, and α-arabinopyranosidase and converted ginsenoside Rb1 and Rb2 to Rd. They also hydrolized cellobiose into glucose. The recombinant enzyme activities of both BLA_0141 and BLA_0893 were stable around pH 4.5–7.5 and below 50°C.

GntK harbors methyltransferase-related cobalamin-binding domain and radical S-adenosylmethionine domain. The gntK-inactivation mutant of Micromonospora echinospora accumulated higher levels of gentamicin Cla and lower levels of gentamicin C1 and C2 isomers compared to the wild-type strain. Based on these results, we propose that GntK is involved in C-methylation on C-6′ in gentamicin X2 but is dispensable in gentamicin biosynthesis.

Newly developed uncovered stents are designed to have varied radial force and high conformability to improve clinical outcome and safety. This study aimed to determine and compare the clinical outcome and safety of the Taewoong D-type uncovered stent and the Boston Scientific Wallfex stent.Patients with acute malignant colonic obstruction were treated with a colonic stent. For the purpose of palliation, patients were randomly allocated. For the purpose of bridging, the type of stent was determined by the discretion of the individual doctors. Technical and clinical success and complication occurrence were measured as primary outcomes.From 12 university hospitals, 123 patients with malignant colonic obstruction were enrolled. Of these 123 patients, 58 were treated with colonic stents for palliative purposes. The technical and clinical success rate was 100 % for both stents in the palliative group. Perforation occurred for one patient (3.6 %) in the Wallflex stent group (n = 28) on day 5 and for no patients in the D-type stent group (n = 30). Two cases of migration occurred: one with the Wallflex stent and one with the D-type stent. Stent restenosis occurred for one patient with the Wallflex stent. Preoperative bridging stents were placed in 65 patients. The median time to surgery was 10 days. The technical success rate was 93.4 %, and clinical success was achieved for 86.2 % of the patients. Perforation occurred for five patients: four with the Wallflex stent and one with the D-type stent. The efficacy and safety of the two stents did not differ statistically.The D-type colonic uncovered stent and the Wallflex colonic uncovered stent are effective and safe for both palliative and preoperative bridging therapy used to treat acute malignant colonic obstruction.

Appropriate surveillance intervals are important to ensure that the benefits of surveillance are not offset by harm. This study aimed to determine the factors associated with nonadherence to recommended colonoscopic surveillance intervals. The study enrolled 296 patients who underwent screening colonoscopy. The colonoscopies were performed by four endoscopists in the first or second year of fellowship. After each procedure, the endoscopists responded to a questionnaire that elicited information on the degree of concern for missed polyps (using a visual analog scale [VAS]), colonoscopic technical factors, and surveillance intervals. Of the 296 patients, 105 (36%) were adherent and 191 (64%) and were nonadherent to the guidelines. There were no differences in insertion time, withdrawal time, or polyp detection rate between the adherence and nonadherence groups. The endoscopy at cecal intubation was longer in the nonadherence group than in the adherence group (P = 0.013). The proportion of patients with poor bowel preparation was higher in the nonadherence group than in the adherence group (P = 0.011). The endoscopist’s concern for missed polyps was greater in the nonadherence group than in the adherence group (P

We investigated the clinical usefulness of HbA1c in screening an average-risk group50 years of age who need colonoscopy for colorectal cancer (CRC) screening.Eight hundred nineteen asymptomatic males who underwent colonoscopy for CRC screening with blood chemistries between January 2006 and December 2006 were enrolled. The ages of the subjects ranged from 40 to 59.Subjects in their 50 s had significantly more adenomatous polyps than subjects in their 40 s (32.7% vs. 26.0%, p0.05). The incidence of adenomatous polyp increased with increasing quartiles of HbA1C as follows: first quartile (19.9%, HbA1c 4.0-5.0), second quartile (27.8%, HbA1c 5.1-5.3), third quartile (32.7%, HbA1c 5.4-5.5), and fourth quartile (34.9%, HbA1c = 5.6-8.8)(p = 0.008). When combining quartile of HbA1c and age (40 s vs. 50 s) according to HbA1C levels, the odds ratio for adenomatous polyp in subjects in their 40 s with HbA1c5.4% was significantly lower than that in subjects in their 50 s. However, the odds ratio for adenomatous polyp in subjects in their 40 s with HbA1cor =5.4% was similar to that in subjects in their 50 s with average risk for CRC.An elevated HbA1c may be useful as a clinical predictor of adenomatous polyps in male subjects50 years of age who have average risk for CRC.

Distal microsatellite instability (MSI)-high colorectal cancers (CRCs) have been investigated by few studies and are generally regarded as having similar features to proximal MSI-high CRCs. In the present study, we aimed to elucidate whether distal sporadic MSI-high CRCs displayed distinguished clinicopathological and molecular features from proximal MSI-high CRCs.All patients who underwent their first surgical resections for stage I-IV sporadic CRCs between August 2003 and August 2006 were initially considered for enrollment, and their MSI data were prospectively collected. Among them, 135 patients with MSI-high CRCs (86 proximal and 49 distal CRCs) were finally identified. The clinicopathological and molecular characteristics, and prognosis of these cases with MSI-high CRCs were reviewed and compared according to tumor site (proximal versus distal).Distal MSI-high CRCs showed significantly more frequent association with younger age, male gender, differentiated histology, small tumor size, distant metastasis, stability in BAT25 and BAT26, and hMLH1 expression on immunohistochemical staining as compared with proximal MSI-high CRCs. In addition, distal MSI-high CRCs demonstrated significantly worse 3-year overall and disease-free survival rates than proximal MSI-high CRCs (87.0% versus 97.4%; 81.6% versus 95.9%). For stage III-IV CRCs, distal MSI-high CRCs also showed significantly worse 3-year overall and disease-free survival rates than proximal MSI-high CRCs (72.2% vs. 90.5%; 58.3% vs. 94.4%).These results indicated that distal sporadic MSI-high CRCs formed a distinct subgroup with distinguished clinicopathological and molecular features from proximal MSI-high CRCs. In addition, this study demonstrated that distal MSI-high CRCs had worse prognosis than proximal MSI-high CRCs.

Degradation of the extracellular matrix is an essential step in tumor invasion and metastasis. It involves the actions of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs). We evaluated the expression of MMP-9 and TIMP-1 in gastric carcinomas and the relationship between this expression and tumor recurrence. Eighty patients who had undergone curative surgical resection for gastric carcinoma were included. Resected gastric tissue samples were stained immunohistochemically to evaluate the expression of MMP-9 and TIMP-1. TIMP-1 expression was related to the depth of tumor invasion and lymph node metastasis. The proportion of tumors larger than 5 cm, or displaying muscle layer invasion, and the cumulative incidence of tumor recurrence were significantly elevated in patients with tumors expressing TIMP-1. Furthermore, these measures were lowest in patients with no TIMP-1 expression and highest in patients who only expressed TIMP-1. In conclusion, TIMP-1 expression and the balance between expression of MMP-9 and expression of TIMP-1 may be important indicators of tumor progression and predictors of tumor recurrence.

In this study, we investigated desulfurization abilities and activation energy using TGA for CuO-AgO sorbents calcined at 700 °C. CuO was used as a main active material and AgO was used as an additive material and 25 wt% SiO2 was used as a support material. The desulfurization reaction temperatures were 450 °C, 500 °C, and 550 °C and the regeneration reaction temperature was 700 °C. From the TGA experiments, the best sulfur loading of CAS1 sorbent containing 1 wt% AgO was about 14.95 g sulfur/100 g sorbent at 550 °C. The activation energy was calculated by the Chatterjee-Conrad method based on the TGA experiment. Desulfurization ability and activation energy of sorbent were decreased as the content of AgO increased.

We investigated the effect of temperature, oxidant and catalyst loading on the performance of direct formic acid fuel cell (DFAFC). When oxidant was changed from air to oxygen, the power density was increased to 17.3 mW/ cm2 at 25 ‡C. The power density of DFAFC operated with oxygen showed a maximum value of 40.04 mW/cm2 with the temperature rise from room temperature to 70 °C. The highest power density of DFAFC using air was observed for Pt-Ru black catalyst with loading of 8 mgPt/cm2 at room temperature. At 70 ‡C; however, the performance of catalyst with the loading of 4 mgPt/cm2 was higher than that of 8 mgPt/cm2. The DFAFC, operated with oxygen and catalyst of 4 mgPt/cm2 loading, showed the best performance at all temperature range. The enhancement of cell performance with an increase of catalyst loading is believed to come from an increase of catalyst active sites. However, operated at higher temperature or with oxygen, the cell with higher catalyst loading showed lower performance than expected. It is speculated that the thick catalyst layer inhibits the proton transport.

Surface acoustic wave (SAW) propagation properties of gallium nitride (GaN) epitaxial layers on sapphire were theoretically and experimentally characterized. GaN thin films were grown on a c-plane sapphire substrate using a metalorganic chemical vapor deposition system. The experimental characterization of SAW propagation properties was performed with a linear array of interdigital transducer structures, while SAW velocities were calculated by matrix methods. Experimentally, we found pseudo-SAW and high-velocity pseudo-SAW modes in the GaN/sapphire structure, which had a good agreement with calculated velocities.

We extend a theorem of Kist for commutative PP rings to principally quasi-Baer rings for which every prime ideal contains a unique minimal prime ideal without using topological arguments. Also decompositions of quasi-Baer and principally quasi-Baer rings are investigated.

Let \(R\) be a unital K-algebra, where K is a commutative ring with unity. An idempotent \(e \in R\) is {\it left semicentral\/} if \(Re = eRe\), and \(R\) is {\it SCI-generated\/} if it is generated as a K-module by left semicentral idempotents. This paper develops the basic properties of SCI-generated algebras and characterizes those that are also prime, semiprime, primitive, or subdirectly irreducible. Minimal ideals and the socle of SCI-generated algebras are investigated. Conditions are found to describe a large class of SCI-generated algebras via generalized triangular matrix representations. SCI-generated piecewise domains are characterized. Examples are given that illustrate the breadth and diversity of the class of SCI-generated algebras.

A chemically induced reduction process has been developed for synthesizing intermetallic matrix composites (IMCs) consisting of titanium aluminide and titanium carbide. The process involves the reduction of metal chlorides (TiCl4 and AlCl3) with metallic lithium in polar organic solvents such as acetonitrile (MeCN) and tetrahydrofuran (THF) to form a colloidal precursor. The as-prepared precursors have been either directly heat treated in ultra-high-purity argon (UHP-Ar) or pretreated in hydrogen (H2) followed by further heat treatment in UHP-Ar. The powders have been characterized primarily using X-ray diffraction (XRD), scanning electron microscopy (SEM), and transmission electron microscopy (TEM). Results of the structural analyses conducted on the heat-treated precursors derived using MeCN as a solvent indicate the formation of either single-phase titanium carbide (TiC) or a composite mixture of γ-TiAl and nanocrystalline TiC, depending on the heat-treatment conditions. The formation of TiC is related to the strong interaction between TiCl4 and the polar organic solvents, resulting in the formation of adducts which contain primary Ti-C linkages. Pretreatment of the precursors derived using MeCN as a solvent in H2 promotes the removal of carbon and results in the formation of the composite mixture of γ-TiAl and TiC after subsequent Ar treatment at 1200 °C. At this stage, washing the pretreated powders in water helps to minimize and even eliminate any impurity phases to a large extent, leaving behind phase-pure composites containing γ-TiAl and TiC after the final Ar treatment. However, extended pretreatment in H2 appears to be ineffective toward removal of additional carbon and leads to formation of hydride-phase impurities. On the other hand, the reductive reaction conducted using THF as a solvent results in minimizing the amount of carbon while inducing the formation of γ-TiAl during direct Ar treatment of the precursors. This is because of the weaker interaction between TiCl4 and THF. Transmission electron microscopy was used to characterize the size distribution of the constituent phases. The analysis shows that the composite synthesized using these chemical approaches consist of discrete nanocrystalline TiC particles (