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Background There is no proven primary preventive strategy for doxorubicin‐induced subclinical cardiotoxicity (DISC), especially among patients without a cardiovascular (CV) risk. We investigated the primary preventive effect on DISC of the concomitant use of angiotensin receptor blockers (ARBs) or beta‐blockers (BBs), especially among breast cancer patients without a CV risk. Methods A total of 385 patients who were scheduled for doxorubicin chemotherapy were screened. Among them, 195 patients of the study populations were included and were randomly divided into two groups [candesartan 4 mg q.d. vs. carvedilol 3.125 mg q.d.] and patients who were unwilling to take one of the medications were evaluated as controls. The primary outcomes were the incidence of early DISC (DISC developing within 6 months after chemotherapy), and late DISC (DISC developing only at least 12 months after chemotherapy). Result Compared with the control group (8 out of 43 patients (18.6%)), only the candesartan group (4 out of 82 patients (4.9%)) showed a significantly lower incidence of early DISC (p = 0.022). Compared with the control group, the candesartan group demonstrated a significantly reduced decrease in left ventricular ejection fraction (LVEF) throughout the study period [−1.0% vs. −3.00 (p, This study showed that low cumulative doses of doxorubicin were associated with the early development of subclinical cardiotoxicity in breast cancer patients without cardiovascular risk. Concomitant treatment with low‐dose candesartan may attenuate and even reverse early left ventricular systolic dysfunction in these patients.

This study examined whether infants assume that people will help others to achieve specific goals. Seventeen-month-old infants watched familiarization events in which a competent agent succeeded in climbing hills while an incompetent agent failed to do so. In subsequent test events, the competent agent either helped the incompetent agent reach the top of the hill (helping event) or simply passed the incompetent agent and reached the top of the hill alone (ignoring event). The infants looked reliably longer at the ignoring event than at the helping event. These findings suggest that, by at least the age of 17 months, infants expect a competent agent to help an incompetent agent. Our findings provide evidence that infants in their second year of life possess some expectations of others' prosociality. Statement of contribution What is already known? Infants begin to reliably produce helping behaviours during their second year of life. Infants expect others to help an agent who is in need, not one who is not in need. Infants expect others to help, not ignore, another in need when linguistic information explicitly signals that the agent and the recipient belong to the same social group. What the present study adds? Infants expect someone to provide help rather than to ignore another in need under some circumstances with no linguistic information about their social group membership. Infants expect an agent to be a helper, not a bystander, even when they lack information about the agent's moral characteristics.

Erythropoiesis-stimulating agents (ESAs), such as erythropoietin (EPO) and darbepoetin, may alleviate anemia in diffuse large B-cell lymphoma (DLBCL) patients. However, many cancer cells express EPO receptors (EPOR), through which exogenously administered ESAs potentially promote cancer cell growth. We conducted preclinical/phase II studies to investigate the safety and efficacy of ESAs for managing chemotherapy-related anemia in DLBCL patients. We examined EPOR expression in germinal center B-cell (GCB)- and activated B-cell (ABC)-DLBCL cell lines, and investigated the effects of ESAs on cell proliferation, and rituximab-mediated complement-dependent cytotoxicity (CDC). The clinical study enrolled 50 histologically confirmed DLBCL patients receiving rituximab/cyclophosphamide/doxorubicin/vincristine/prednisolone (R-CHOP) who had hemoglobin levels

BACKGROUND Eradication rate of standard triple therapy for H. pylori has declined to unacceptable level, and alternative regimens such as concomitant and sequential therapy have been introduced. We aimed to assess the consistency of eradication rates of concomitant and sequential therapies as for the first-line H. pylori eradication in Korea. METHODS A nationwide multicenter retrospective study was conducted including 18 medical centers from January 2008 to December 2017. We included 3,800 adults who had test to confirm H. pylori eradication within 1 year after concomitant or sequential therapy. RESULTS Concomitant and sequential therapy were prescribed for 2508 and 1292 patients, respectively. The overall eradication rate of concomitant therapy was significantly higher than that of sequential therapy (91.8% vs. 86.1%, p

We propose a cross-scanning optical coherence tomography (CS-OCT) system to correct eye motion artifacts in OCT angiography images. This system employs a dual-illumination configuration with two orthogonally polarized beams, each of which simultaneously perform raster scanning in perpendicular direction with each other over the same area. In the reference arm, a polarization delay unit is used to acquire the two orthogonally polarized interferograms with a single photo detector by introducing different optical delay lines. The two cross-scanned volume data are affected by the same eye motion but in two orthogonal directions. We developed a motion correction algorithm, which removes artifacts in the slow axis of each angiogram using the other and merges them through a nonrigid registration algorithm. In this manner, we obtained a motion-corrected angiogram within a single volume scanning time without additional eye-tracking devices.

This study investigated 6- and 10-month-old infants' abilities to infer others' preferences based on social interactions using looking time and choice measures. Infants were randomly assigned to either a helping/neutral or hindering/neutral condition. Those in the helping/neutral condition were first familiarized with a helping event, in which an agent helped a circle climb a hill, and a neutral event, in which another agent followed the same path as the helping agent but had no interaction with the circle. During the test phase, the circle approached either the helper or the neutral agent. In the hindering/neutral condition, the infants were familiarized with a hindering event, in which an agent hindered the circle from reaching the top of the hill, and a neutral event, in which another agent followed the same path as the hindering agent but had no interaction with the circle. During the test phase, the circle approached either the hinderer or the neutral agent. For the looking-time measure, infants in the hindering/neutral condition looked reliably longer at the approach-hinderer than at the approach-neutral agent event, whereas those in the helping/neutral condition looked for equal amounts of time at both test events. These results suggest that the infants expected the circle to avoid the hinderer but did not expect it to approach the helper. In the choice task, infants chose the helper more often than the neutral agent and the neutral agent more often than the hinderer, suggesting an ability to generate their own preferences for a particular agent based on the valence of helping and hindering actions. This research demonstrates infants' sensitivity to the moral valence of agents' social interactions, which may serve as a foundation for advanced socio-moral reasoning. Statement of contribution What is already known on this subject? Research on infants' ability in social evaluation has established that even preverbal infants can distinguish between positive and negative social interactions. Infants as young as 6 months of age can distinguish between helping and hindering actions and can generate their own preference towards helpful agents. What does this study add? The present study sheds light on infants' ability to infer a third-party's preference, which is a more challenging task for the infants than generating their own preference. Specifically, 6- and 10-month-old infants could infer others' preference for the neutral agent over the hinderer. Such results demonstrate infants' sensitivity to the moral valence of agents' social interactions and provide an evidence of negativity bias in social evaluation.

Background The Helicobacter pylori eradication rate has decreased with increasing antibiotic resistance. We conducted a prospective, nationwide, multicenter registry study to monitor the real status of H. pylori eradication therapy and to investigate the association between eradication success and antibiotic use density in Korea. Materials and Methods We enrolled 9318 patients undergoing H. pylori eradication therapy from 37 hospitals through “on‐line database registry” from October 2010 to July 2015. Demographic data, detection methods, treatment indications, regimens, durations, compliance, adverse events, and eradication results were collected. The use of all commercially available eradication antibiotics was analyzed through the Korean National Health Insurance data of the Health Insurance Review and Assessment Service. The defined daily dose of antibiotics was used to standardize drug use comparisons. Results Finally, 6738 patients were analyzed. The overall eradication rate of first‐line therapy was 71.8%. The eradication success rates were 71.7%, 86.9%, and 74.0% for standard triple therapy for 7 days, quadruple therapy, and concomitant therapy, respectively. The eradication success rate in naive patients was higher than that in those who previously underwent H. pylori eradication. Eradication success was significantly associated with younger age, female sex, and high compliance. Regional differences in eradication rates were observed. The yearly use density of clarithromycin increased statistically in seven regions across the country from 2010 to 2015. The yearly use density of amoxicillin in the Gyeongsang and Chungcheong areas was significantly increased (P

Purpose To evaluate apparent diffusion coefficient (ADC) histogram parameters that show correlations with prognostic factors and subtypes of breast cancer. Materials and Methods At 3.0T, various ADC histogram parameters were calculated including the entire tumor volume in 173 invasive ductal carcinomas: the minimum, 10th percentile, mean, median, 90th percentile, and maximum. ADC parameters were correlated with prognostic factors and subtype. Results The mean ADCmedian value was significantly higher in the group with lymph node metastasis, HER2 positivity, and a Ki-67 value

Background and Objectives More superficially located tumors may be more likely than deeper tumors to metastasize to the axillary nodes via the lymphatics. The aim of this study was to determine whether breast cancer distance from the skin affects axillary node metastasis, ipsilateral breast cancer recurrence, or recurrence-free survival. Materials and Methods A total of 1,005 consecutive patients with breast cancer who underwent surgery between January 2003 and December 2009 were selected. The distance of the tumor from the skin was measured from the skin to the most anterior hypoechoic leading edge of the lesion. Results In total, 603 (68%) patients had no axillary nodal metastasis, and 288 (32%) had axillary nodal metastasis. A breast cancer distance from the skin

Protein degradation by the ubiquitin-proteasome system (UPS) affects many biological processes. Inhibition of the proteasome has emerged as a potential therapeutic target for cancer treatment. In this study, we developed a method for monitoring the degradation and accumulation of UPS-dependent substrates in cells using CE with dual LIF. We used a green fluorescent protein (GFP)-fusion of the ubiquitin substrate ribophorin 1 (GFP-RPN1) along with red fluorescent protein (RFP) as an internal control to normalize transfection efficiency. Determination of GFP-RPN1 and RFP in cell lysates were performed in an untreated capillary (75 μm × 50 cm) and 100 mM Tris-CHES buffer (pH 9.0) containing 10 mM SDS. GFP-RPN1 and RFP fluorescence were detected at excitation wavelengths of 488 and 635 nm, and emission wavelengths of 520 and 675 nm, respectively, without any interference or crosstalk. The intensity of GFP-RPN1 fluorescence was normalized to that of RFP. Additionally, the proposed approach was used successfully to detect the degradation of GFP-RPN1 and evaluate proteasome inhibitors. These results show that the developed method is effective and promising for rapid and quantitative monitoring of UPS-dependent substrates compared to the current common methods, such as immunoblotting and pulse chase assays.

Purpose Receptor activator of nuclear factor kappa-B and its ligand (RANK/RANKL) and Osteoprotegerin (OPG) are key molecules for regulating osteoclastic activity in bone. However, little is known about the role of RANK-related molecules in breast cancer prognosis. We aimed to evaluate RANK, RANKL, and OPG expression and the associated clinical impact in breast cancer. Methods Tissue microarray (TMA) from 185 patients with primary breast cancer was established. Immunohistochemistry for RANK, RANKL, and OPG was performed. Clinicopathologic features and survival outcomes associated with expression of RANK, RANKL, and OPG were analyzed. Results RANK, RANKL, and OPG were expressed in 74.1%, 78.4%, and 45.9% of patients, respectively. RANKL expression was associated with lower Ki-67 level. OPG expression was related to small tumor size, node negativity, and low Ki-67. There was no significant difference in clinicopathologic features between tumors with RANK and those without RANK. RANK expression was significantly associated with poor disease-free survival in univariate analysis (P = 0.04) and multivariate analysis (P = 0.02). RANKL expression was associated with improved skeletal disease-free survival in multivariate analysis (P = 0.03). Conclusions The RANK/RANKL pathway regulated by OPG may have a role in predicting progression and prognosis of breast cancer. J. Surg. Oncol. 2014 110:807–812. © 2014 Wiley Periodicals, Inc.

Background and Aim Although differences in genetic susceptibility and the clinical features of Crohn's disease (CD) have been reported between Asian and Caucasian patients, the disease course and predictors of CD in Asians remains poorly defined. The study therefore aimed to investigate factors predictive of the clinical outcomes of patients with CD in a Korean population. Methods This retrospective multicenter cohort study included 728 Korean CD patients from 13 university hospitals. The first CD-related surgery or need for immunosuppressive or biological agents were regarded as the clinical outcomes of interest. Results A total of 126 (17.3%) CD patients underwent CD-related surgery, while 473 (65.0%) and 196 (26.9%) were prescribed thiopurine drugs and infliximab, respectively. Multivariate Cox regression analysis identified current (hazard ratio [HR] = 1.86; P = 0.018) and former smoking habits (HR = 1.78; P = 0.049), stricturing (HR = 2.24; P

For decades, a spirited debate has existed over whether infants’ remarkable capacity to learn words is shaped primarily by universal features of human language or by specific featuers of the particulare native language they are acquiring. A strong focus for this debate has been a well-documented difference in early word learning: Infants’ success in learning verbs lags behind their success in learning nouns.. In this review, we articulate both sides of the debate and summarize new cross-linguistic evidence from infants that underscores the role of universal features and begins to clarify the impact of distinctly different languages on early language and conceptual development.

Micro-RNAs (miRNAs) are small, endogenous, singlestranded, and noncoding RNAs. The miRNAs have been found to perform important functions in many cellular processes, such as development, proliferation, differentiation, and apoptosis. Circulating miRNAs have been proposed as emerging biomarkers in diseases such as cancer, diabetes, and cardiovascular disease including acute myocardial infarction (AMI). In this study, we developed CE with LIF (CE-LIF) using fluorescence-labeled DNA probe for determination of low abundance miRNA in cell extracts. The target miRNA is miRNA-499, a biomarker candidate of AMI with low abundance in biological samples. In order to measure the trace level of miRNA, we optimized the hybridization conditions such as hybridization time, temperature, and buffer solution. The highest fluorescence intensity of the hybridized miRNA-499 was found when hybridization was conducted at 40°C in 50 mM Tris-acetate (pH 8.0) buffer containing 50 mM NaCl, and 10 mM EDTA for 15 min. The hybridized miRNA-499 was detected in cultured H9c2 cardiomyoblast cells and the analysis of miRNA-499 was completed within 1 h using CE-LIF. These results showed the potential of CE for fast, specific, and sensitive high-throughput analysis of low-abundance miRNAs in cell extracts, biofluids, and tissues.

Dual-specificity tyrosine(Y)-phosphorylation-regulated kinase 1A (Dyrk1A) is a protein kinase that might be responsible for mental retardation and early onset of Alzheimer's disease in Down's syndrome patients. Dyrk1A plays a role in many cellular pathways through phosphorylation of diverse substrate proteins; however, its role in synaptic vesicle exocytosis is poorly understood. Munc18-1, a central regulator of neurotransmitter release, interacts with Syntaxin 1 and X11α. Syntaxin 1 is a key soluble N-ethylmaleimide-sensitive factor attachment protein receptor protein involved in synaptic vesicle docking/fusion events, and X11α modulates amyloid precursor protein processing and β amyloid generation. In this study, we demonstrate that Dyrk1A interacts with and phosphorylates Munc18-1 at the Thr(479) residue. The phosphorylation of Munc18-1 at Thr(479) by Dyrk1A stimulated binding of Munc18-1 to Syntaxin 1 and X11α. Furthermore, the levels of phospho-Thr(479) -Munc18-1 were enhanced in the brains of transgenic mice over-expressing Dyrk1A protein, providing in vivo evidence of Munc18-1 phosphorylation by Dyrk1A. These results reveal a link between Munc18-1 and Dyrk1A in synaptic vesicle trafficking and amyloid precursor protein processing, suggesting that up-regulated Dyrk1A in Down's syndrome and Alzheimer's disease brains may contribute to some pathological features, including synaptic dysfunction and cognitive defect through abnormal phosphorylation of Munc18-1.

Background Eosinophilic bronchitis (EB) is a common cause of chronic cough. Although EB shares many immunopathologic features with asthma, it does not show airway hyperresponsiveness or reversible airway obstruction by spirometry. Objective Compared to healthy children without pulmonary disease, we hypothesized that EB patients would demonstrate abnormal pulmonary function and inflammation with impulse oscillometry (IOS) and fractional exhaled nitric oxide (FeNO), which are more sensitive tests of these parameters than spirometry. Methods A total of 232 children with asthma, 109 with EB, and 115 control subjects were enrolled. We compared pulmonary function parameters and FeNO levels among the three groups. Additionally, we designated a screening cutoff value of FeNO combined with IOS parameters to distinguish EB from the control group, and identify which children with EB have more asthmatic characteristics. Results By IOS, the bronchodilator response of the EB and asthma groups increased significantly compared to controls for both reactance at 5 Hz (Δ X5) and reactance area (Δ AX) (P

The impact of electronically-active native point defects on ZnO optoelectronic technologies at the nanoscale is only now being explored. We are able to address the impact of these defects on Schottky barrier formation and doping using a combination of depth-resolved and scanned probe techniques. We clearly identify the optical transitions and energies of VZn and VZn clusters, Ga on Zn site donors, Li on Zn sites, the effects of different annealing methods on their spatial distributions in ion-implanted as well as Ga grown-in ZnO, and how VZn, VZn clusters, and VO complexes contribute to near- and sub-surface carrier density. These results reveal the interplay between ZnO electronic defects, polarity, and surface nanostructure. Overall, the influence of native point defects on doping, Schottky barriers, and transport point to new ways for controlling these properties (© 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)

Omics is the study of proteins, peptides, genes, and metabolites in living organisms. Systems biology aims to understand the system through the study of the relationship between elements such as genes and proteins in biological system. Recently, systems biology emerged as the result of the advanced development of high-throughput analysis technologies such as DNA sequencers, DNA arrays, and mass spectrometry for omics studies. Among a number of analytical tools and technologies, CE and CE coupled to MS are promising and relatively rapidly developing tools with the potential to provide qualitative and quantitative analyses of biological molecules. With an emphasis on CE for systems biology, this review summarizes the method developments and applications of CE for the genomic, transcriptomic, proteomic, and metabolomic studies focusing on the drug discovery and disease diagnosis and therapies since 2009.

Over the past decade, dye-sensitized solar cells (DSSCs) based on nanocrystalline mesoporous metal oxides (typically TiO2) have been intensively studied and developed as a promising, low-cost alternative to conventional silicon photovoltaic devices. The components of such DSSCs are a dye sensitizer, a TiO2 metal oxide coated on conductive glass, a redox electrolyte couple, and a counter electrode. As illustrated in Scheme 1, the power-conversion efficiency of DSSCs is strongly dependent upon the minimization of charge recombination losses at the TiO2/dye/electrolyte interface (pathways 3 and 4). There are two recombination pathways of importance in DSSCs, in which electrons photoinjected into the TiO2 electrode can recombine with either dye cations or with redox electrolytes. Moreover, such charge recombination leads to losses in both the short-circuit photocurrent (Jsc) and the open-circuit photovoltage (Voc), resulting in a decrease in overall energy conversion efficiency (h). To reduce the possible charge recombination pathways occurring at the TiO2/dye/electrolyte interface, several kinds of additives, such as decylphosophonic acid (DPA), dineohexyl bis(3,3-dimethylbutyl)phosphinic acid (DINHOP), and chenodeoxycholic acid (CDCA) have been introduced to adsorb onto the TiO2 surface. [3] Among them, for example, cholic acid (CA) derivatives as coadsorbents in DSSCs, based on a Ru–pyridyl complex, courmarin, porphyrin, phthalocyanine, and naphthalocyanine dye, have been investigated well. Deoxycholic acid (DCA) is often used as a coadsorbent to break up organic and Ru–dye aggregates and hence to significantly improve Voc and Jsc. [5,9] Moreover, alternative approaches directed toward the minimization of recombination losses have been extensively studied by not only the insertion of a metal oxide blocking layer, but also by energetic cascades for multistep hole conductors (HC), as well as superior molecular sensitizer dyes and the insertion of a barrier layer between the sensitizer dye and the HC. To date, however, the desired redox intermediate mediators between the dye and I /I3 redox electro

Objectives The purpose of this study was to evaluate the diagnostic utility of sonographic elastography in differentiating reactive and metastatic axillary lymph nodes in breast cancer. Methods A total of 64 lymph nodes (reactive, n = 33; metastatic, n = 31) from 62 patients with breast cancer were examined by both B-mode sonography and elastography from April to July 2009. Two experienced radiologists retrospectively assessed B-mode sonograms by the sum of scores for 4 criteria: short diameter, shape, hilum, and cortical thickening. Elastographic images were given scores of 1 to 4 according to the percentage of high-elasticity areas in the lymph nodes. We compared the diagnostic performance of B-mode sonography, elastography, and combined examinations. We also calculated the strain ratio of the lymph node and subcutaneous fat tissue. Results The elasticity score for malignant lymph nodes (mean, 3.1) was higher than the score for benign lymph nodes (mean, 2.2; P < .0001). With a cutoff between elasticity scores of 2 and 3, elastography showed 80.7% sensitivity, 66.7% specificity, and 73.4% accuracy. With a cutoff between B-mode sonographic scores of 1 and 2, B-mode sonography showed 74.2% sensitivity and 78.8% specificity. Combined B-mode and elastographic sonography showed higher sensitivity (87.1%) than B-mode sonography alone. With a strain ratio cutoff point of 2.3, sensitivity was 82.8%, and specificity was 56.3%. Conclusions Sonographic elastography may increase the sensitivity of B-mode sonography in the detection of metastatic axillary lymph nodes.

Background The functions of nuclear receptor DAX-1 and androgen receptor (AR) in breast cancer are unknown and have not been well-characterized in terms of their importance as a predictive or a prognostic factor. The study investigated the relationship between expression of AR, DAX-1, and clinicopathological factors in primary breast cancer patients. Methods The data of 476 breast cancer patients who were treated at Seoul St. Mary's hospital from January 2004 to March 2006 were reviewed. Among them, 169 cases (35.5%) were consecutively evaluated for AR and DAX-1 expression. Results DAX-1 expression was associated with smaller tumor size; earlier disease stage; and higher expression of estrogen receptor (ER), progesterone receptor (PgR) and AR. AR was significantly expressed in patients with smaller tumor size and higher expression of ER, PgR, and DAX-1. In the subgroup analysis of triple negative breast cancer patients, the expression rate of DAX-1 (4/12, 33.3%) was higher than AR (1/12, 8.3%). Conclusions The present review revealed a very high expression rate of DAX-1 in human breast cancer (74%). DAX-1 might modify steroidogenic hormone systems like as AR, estrogen receptor, and progesterone receptor. DAX-1 might be a more effective target than AR for triple negative breast cancer. J. Surg. Oncol. 2011;103:768–772. © 2011 Wiley-Liss, Inc.

It is well known that the two chemical compounds endothelin-1 (ET-1) and isoproterenol (ISO) can individually induce cardiac hypertrophy through G protein-coupled receptors in cardiomyocytes. However, the cardiac hypertrophy signaling pathway activated by ET-1 and ISO is not well defined. Therefore, we investigated the protein expression profile and signaling transduction in HL-l cardiomyocyte cells treated with ET-1 and ISO. Following separation of the cell lysates by using 2-DE and silver staining, we identified 16 protein spots that were differentially expressed as compared to the controls. Of these 16 spots, three changed only after treatment with ET-1, whereas four changed only after treatment with ISO, suggesting that these two stimuli could induce different signaling pathways. In order to reveal the differences between ET-1- and ISO-induced signaling, we studied the different events that occur at each step of the signaling pathways, when selected biocomponents were blocked by inhibitors. Our results indicated that ET-1 and ISO used different pathways for phosphorylation of glycogen synthase kinase-3β (GSK3β). ET-1 mainly used the mitogen-activated protein kinase and phosphatidylinositol-3-kinase/AKT pathways to activate GSK3β, whereas under ISO stimulation, only the phosphatidylinositol-3-kinase/AKT pathway was required to trigger the GSK3β pathway. Furthermore, the strength of the GSK3β signal in ISO-induced cardiac hypertrophy was stronger than that in ET-1-induced cardiac hypertrophy. We found that these two agonists brought about different changes in the protein expression of HL-1 cardiomyocytes through distinct signaling pathways even though the destination of the two signaling pathways was the same.

An analytical method of CE-MS and CE with an online preconcentration technique induced by a dynamic pH junction, addition of organic solvent and large volume injection was developed for sensitive determination of peptides in biological samples. Leucine enkephalin, methionine enkephalin, dynorphin A, β-endorphin and angiotensin II were used as model peptides. The optimal online preconcentration conditions were obtained at a sample matrix consisting of 100 mM borate buffer (pH 10.0) with 50% v/v acetonitrile and a BGE containing 1 M formic acid at pH 2.0, along with a 25-cm injection length. Under the optimized conditions, a 4.0 x 10 1 -1.1 × 10 4 -fold increase in peak intensity was achieved without degrading the peak shape. This online preconcentration method was applied to analyze the intracellular angiotensin II within the peptides extracted from HL1 cells and approximately increase of 1 × 10 4 -fold sensitivity was achieved compared to normal condition. Thus, the developed method could be applied to the analysis of various peptides for peptidomics study in biological samples.

The dual-specificity tyrosine(Y)-phosphorylation-regulated kinase 1A (Dyrk1A) gene is located on human chromosome 21 and encodes a proline-directed protein kinase that might be responsible for mental retardation and early onset of Alzheimer's disease (AD) in Down syndrome (DS) patients. Presenilin 1 (PS1) is a key component of the γ-secretase complex in the generation of β-amyloid (Aβ), an important trigger protein in the pathogenesis of AD. Increased Dyrk1A expression has been reported in human AD and DS brains. We previously showed that Dyrk1A increased Aβ production in mammalian cells and transgenic mice that over-express Dyrk1A. In this study, we describe a potential mechanism by which Aβ is increased in Dyrk1A-over-expressing DS and AD brains. First, we show that PS1 is phosphorylated by the Dyrk1A at Thr(354) and that this phosphorylation increases γ-secretase activity. Then, using transgenic mice that over-express human Dyrk1A, we demonstrate that phospho-Thr354-PS1 (pT354-PS1) expression is enhanced when Dyrk1A level is increased. We also show that pT354-PS1 is more stable than the unphosphorylated form of PS1. These results reveal a potential regulatory link between Dyrk1A and PS1 in the Aβ pathway of DS and AD brains, suggesting that up-regulated Dyrk1A may accelerate AD pathogenesis through PS1 phosphorylation.

Reversible protein phosphorylation and dephosphorylation are very important activities in understanding cellular signaling networks. In this paper we described a CE-LIF-based assay method of calcineurin (CN), a protein phosphatase important in cardiac hypertrophy, in which a fluorescence-labeled 19-amino acid phosphopeptide was used as a substrate. The substrate was converted to a dephosphorylated product by CN and both the substrate and product were detected by the LIF detector. This assay method was tested for various separation parameters as well as reaction parameters. It was found that 100 mM of a boric acid buffer with a pH of 9.00 produced optimum separation at 10 kV of applied voltage using a 47 cm capillary. After obtaining the suitable reaction conditions the method was used to detect and quantify the CN activity in HL-1 cell extracts where the picogram level of CN activity was obtained per microgram total protein. It was also observed that immunosuppressive drugs like okadaic acid and cyclosporine A inhibit in vitro CN activity.

Most individuals with Down Syndrome (DS) show an early-onset of Alzheimer's disease (AD), which potentially results from the presence of an extra copy of a segment of chromosome 21. Located on chromosome 21 are the genes that encode beta-amyloid (Abeta) precursor protein (APP ), a key protein involved in the pathogenesis of AD, and dual-specificity tyrosine(Y)-phosphorylation regulated kinase 1A (DYRK1A ), a proline-directed protein kinase that plays a critical role in neurodevelopment. Here, we describe a potential mechanism for the regulation of AD pathology in DS brains by DYRK1A-mediated phosphorylation of APP. We show that APP is phosphorylated at Thr668 by DYRK1A in vitro and in mammalian cells. The amounts of phospho-APP and Abeta are increased in the brains of transgenic mice that over-express the human DYRK1A protein. Furthermore, we show that the amounts of phospho-APP as well as those of APP and DYRK1A are elevated in human DS brains. Taken together, these results reveal a potential regulatory link between APP and DYRK1A in DS brains, and suggest that the over-expression of DYRK1A in DS may play a role in accelerating AD pathogenesis through phosphorylation of APP.

Vascular tumors of the breast are uncommon and include angiosarcomas and hemangiomas 1 Angiosarcomas are more common, but benign hemangiomas are rare. Furthermore, venous hemangiomas are extremely rare, and we found only a few reports. 2,3 We report a rare case of a pathologically diagnosed venous hemangioma of the breast and describe the imaging and pathologic features.

The emerging field of quantitative systems biology uses high-throughput bioanalytical measurements to gain a deeper understanding of biological phenomena. With the advent of instrumentation platforms, capillary electrophoresis spans a very wide range of biological applications. This short article focuses on the exploitation of capillary electrophoresis for the systems-level analysis of cell signaling molecules. Copyright © 2007 John Wiley & Sons, Ltd.

Emerging systems biology aims at integrating the enormous amount of existing omics data in order to better understand their functional relationships at a whole systems level. These huge datasets can be obtained through advances in high-throughput, sensitive, precise, and accurate analytical instrumentation and technological innovation. Separation sciences play an important role in revealing biological processes at various omic levels. From the perspective of systems biology, CE is a strong candidate for high-throughput, sensitive data generation which is capable of tackling the challenges in acquiring qualitative and quantitative knowledge through a system-level study. This review focuses on the applicability of CE to systems-based analytical data at the genomic, transcriptomic, proteomic, and metabolomic levels.

This paper reports on our investigation of DC and RF characteristics of p-channel metal oxide semiconductor field effect transistors (pMOSFETs) with a compressively strained Si0.8Ge0.2 channel. Because of enhanced hole mobility in the Si0.8Ge0.2 buried layer, the Si0.8Ge0.2 pMOSFET showed improved DC and RF characteristics. We demonstrate that the 1/f noise in the Si0.8Ge0.2 pMOSFET was much lower than that in the all-Si counterpart, regardless of gate-oxide degradation by electrical stress. These results suggest that the Si0.8Ge0.2 pMOSFET is suitable for RF applications that require high speed and low 1/f noise.

With Ni/Au and Pd/Au metal schemes and low temperature processing, we formed low resistance stable Ohmic contacts to p-type GaN. Our investigation was preceded by conventional cleaning, followed by treatment in boiling HNO 3 :HCl (1:3). Metallization was by thermally evaporating 30 nm Ni/15 nm Au or 25 nm Pd/15 nm Au. After heat treatment in O 2 + N 2 at various temperatures, the contacts were subsequently cooled in liquid nitrogen. Cryogenic cooling following heat treatment at 600 °C decreased the specific contact resistance from 9.84×10 -4 Ωcm 2 to 2.65×10 -4 Ωcm 2 for the Ni/Au contacts, while this increased it from 1.80×10 -4 Ωcm 2 to 3.34×10 -4 Ωcm 2 for the Pd/Au contacts. The Ni/Au contacts showed slightly higher specific contact resistance than the Pd/Au contacts, although they were more stable than the Pd contacts. X-ray photoelectron spectroscopy depth profiling showed the Ni contacts to be NiO followed by Au at the interface for the Ni/Au contacts, whereas the Pd/Au contacts exhibited a Pd:Au solid solution. The contacts quenched in liquid nitrogen following sintering were much more uniform under atomic force microscopy examination and gave a 3 times lower contact resistance with the Ni/Au design. Current-voltage-temperature analysis revealed that conduction was predominantly by thermionic field emission.

High-quality and large-area molybdenum disulfide (MoS2) thin film is highly desirable for applications in large-area electronics. However, there remains a challenge in attaining MoS2 film of reasonable crystallinity due to the absence of appropriate choice and control of precursors, as well as choice of suitable growth substrates. Herein, a novel and facile route is reported for synthesizing few-layered MoS2 film with new precursors via chemical vapor deposition. Prior to growth, an aqueous solution of sodium molybdate as the molybdenum precursor is spun onto the growth substrate and dimethyl disulfide as the liquid sulfur precursor is supplied with a bubbling system during growth. To supplement the limiting effect of Mo (sodium molybdate), a supplementary Mo is supplied by dissolving molybdenum hexacarbonyl (Mo(CO)6) in the liquid sulfur precursor delivered by the bubbler. By precisely controlling the amounts of precursors and hydrogen flow, full coverage of MoS2 film is readily achievable in 20 min. Large-area MoS2 field effect transistors (FETs) fabricated with a conventional photolithography have a carrier mobility as high as 18.9 cm2 V−1 s−1, which is the highest reported for bottom-gated MoS2-FETs fabricated via photolithography with an on/off ratio of ≈105 at room temperature.

Multilayer AlGaN/GaN epitaxial structures were grown on SiC by HVPE method. Characterization of the grown structures was performed using SEM, SIMS, mercury probe, electroluminescence and photoluminescence techniques. Thicknesses of nitride layers in nanometer range were achieved. Stimulated emission from double confined heterostructure grown by HVPE was detected at room temperature under optical pumping. Short wave UV electroluminescence (λ max 340-350 nm) was measured for p-AlGaN/n-AlGaN structures having up to 38 mol% and 9 mol% of AIN in p-AlGaN carrier emitter layers and n-AlGaN light emitting layers, respectively.

Stable aqueous colloids of 2−3 nm In2S3 nanocrystals have been prepared by using the classical method of nanoparticle stabilization by low molecular weight thiols. TEM crystal lattice spacing, X-ray diffraction, EDAX data, and electron diffraction indicate that the nanoparticles are predominantly in β-In2S3 form. They exhibit relatively strong excitonic emission at 360−380 nm with a quantum yield of 1.5%. The excitonic radiative lifetime is 350 ns, which indicates that a direct allowed electronic transition is responsible for this emission. The NMR lines of the stabilizer are strongly broadened and shifted as a result of deshielding induced by electron withdrawing by positively charged metal ions. This effect quickly wears off as the carbon chain becomes longer and the separation between the hydrogen atoms of the stabilizer and the semiconductor surface increases. The broadening is attributed to the reduced mobility of the stabilizer in the nanoparticle shell. For CdS nanoparticles of the same size, this ...