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1.  Landau levels and magneto-transport property of monolayer phosphorene 
Scientific Reports  2015;5:12295.
We investigate theoretically the Landau levels (LLs) and magneto-transport properties of phosphorene under a perpendicular magnetic field within the framework of the effective k·p Hamiltonian and tight-binding (TB) model. At low field regime, we find that the LLs linearly depend both on the LL index n and magnetic field B, which is similar with that of conventional semiconductor two-dimensional electron gas. The Landau splittings of conduction and valence band are different and the wavefunctions corresponding to the LLs are strongly anisotropic due to the different anisotropic effective masses. An analytical expression for the LLs in low energy regime is obtained via solving the decoupled Hamiltonian, which agrees well with the numerical calculations. At high magnetic regime, a self-similar Hofstadter butterfly (HB) spectrum is obtained by using the TB model. The HB spectrum is consistent with the LL fan calculated from the effective k·p theory in a wide regime of magnetic fields. We find the LLs of phosphorene nanoribbon depend strongly on the ribbon orientation due to the anisotropic hopping parameters. The Hall and the longitudinal conductances (resistances) clearly reveal the structure of LLs.
PMCID: PMC4498330  PMID: 26159856
2.  Atomic-Scale Interfacial Magnetism in Fe/Graphene Heterojunction 
Scientific Reports  2015;5:11911.
Successful spin injection into graphene makes it a competitive contender in the race to become a key material for quantum computation, or the spin-operation-based data processing and sensing. Engineering ferromagnetic metal (FM)/graphene heterojunctions is one of the most promising avenues to realise it, however, their interface magnetism remains an open question up to this day. In any proposed FM/graphene spintronic devices, the best opportunity for spin transport could only be achieved where no magnetic dead layer exists at the FM/graphene interface. Here we present a comprehensive study of the epitaxial Fe/graphene interface by means of X-ray magnetic circular dichroism (XMCD) and density functional theory (DFT) calculations. The experiment has been performed using a specially designed FM1/FM2/graphene structure that to a large extent restores the realistic case of the proposed graphene-based transistors. We have quantitatively observed a reduced but still sizable magnetic moments of the epitaxial Fe ML on graphene, which is well resembled by simulations and can be attributed to the strong hybridization between the Fe 3dz2 and the C 2pz orbitals and the sp-orbital-like behavior of the Fe 3d electrons due to the presence of graphene.
PMCID: PMC4491707  PMID: 26145155
3.  Gas Sensing Properties of Epitaxial LaBaCo2O5.5+δ Thin Films 
Scientific Reports  2015;5:10784.
Chemical reactivity and stability of highly epitaxial mixed-conductive LaBaCo2O5.5+δ (LBCO) thin films on (001) LaAlO3 (LAO) single-crystalline substrates, fabricated by using pulsed laser deposition system, were systematically investigated. Microstructure studies from x-ray diffraction indicate that the films are c-axis oriented with the interface relationship of [100]LBCO//[100]LAO and (001)LBCO//(001)LAO. LBCO thin films can detect the ethanol vapor concentration as low as 10ppm and the response of LBCO thin film to various ethanol vapor concentrations is very reliable and reproducible with the switch between air and ethanol vapor. Moreover, the fast response of the LBCO thin film, as the p-type gas sensor, is better than some n-type oxide semiconductor thin films and comparable with some nanorods and nanowires. These findings indicate that the LBCO thin films have great potential for the development of gas sensors in reducing/oxidizing environments.
PMCID: PMC4491845  PMID: 26146369
4.  Novel VN/C nanocomposites as methanol-tolerant oxygen reduction electrocatalyst in alkaline electrolyte 
Scientific Reports  2015;5:11351.
A novel VN/C nanostructure consisting of VN nanoparticles and graphite-dominant carbon layers is synthesized by nitridation of V2O5 using melamine as reductant under inert atmosphere. High crystalline VN nanoparticles are observed to be uniformly distributed in carbon layers with an average size of ca13.45 nm. Moreover, the electrocatalytic performance of VN/C towards oxygen reduction reaction (ORR) in alkaline electrolyte is fascinating. The results show that VN/C has a considerable ORR activity, including a 75 percent value of the diffusion-limited current density and a 0.11 V smaller value about the onset potential with respect to Pt/C catalyst. Moreover, the excellent methanol-tolerance performance of VN/C has also been verified with 3 M methanol. Combined with the competitive prices, this VN/C nanocomposite can serve as an appropriate non-precious methanol-tolerant ORR catalyst for alkaline fuel cells.
PMCID: PMC4477409  PMID: 26100367
5.  Model-based Physiomarkers of Cerebral Hemodynamics in Patients with Mild Cognitive Impairment 
Medical engineering & physics  2014;36(5):628-637.
In our previous studies, we have introduced model-based "unctional biomarkers"or "hysiomarkers"of cerebral hemodynamics that hold promise for improved diagnosis of early-stage Alzheimer’s disease (AD). The advocated methodology utilizes subject-specific data-based dynamic nonlinear models of cerebral hemodynamics to compute indices (serving as possible diagnostic physiomarkers) that quantify the state of cerebral blood flow autoregulation to pressure-changes (CFAP) and cerebral CO2 vasomotor reactivity (CVMR) in each subject. The model is estimated from beat-to-beat measurements of mean arterial blood pressure, mean cerebral blood flow velocity and end18 tidal CO2, which can be made reliably and non-invasively under resting conditions. In a previous study, it was found that a CVMR index quantifying the impairment in CO2 vasomotor reactivity correlates with clinical indications of early AD, offering the prospect of a potentially useful diagnostic tool. In this paper, we explore the use of the same model-based indices for patients with amnestic Mild Cognitive Impairment (MCI), a preclinical stage of AD, relative to a control subjects and clinical cognitive assessments. It was found that the model-based CVMR values were lower for MCI patients relative to the control subjects.
PMCID: PMC4076301  PMID: 24698010
6.  Use of lectins to in situ visualize glycoconjugates of extracellular polymeric substances in acidophilic archaeal biofilms 
Microbial Biotechnology  2014;8(3):448-461.
Biofilm formation and the production of extracellular polymeric substances (EPS) by meso- and thermoacidophilic metal-oxidizing archaea on relevant substrates have been studied to a limited extent. In order to investigate glycoconjugates, a major part of the EPS, during biofilm formation/bioleaching by archaea on pyrite, a screening with 75 commercially available lectins by fluorescence lectin-binding analysis (FLBA) has been performed. Three representative archaeal species, Ferroplasma acidiphilum DSM 28986, Sulfolobus metallicus DSM 6482T and a novel isolate Acidianus sp. DSM 29099 were used. In addition, Acidianus sp. DSM 29099 biofilms on elemental sulfur were studied. The results of FLBA indicate (i) 22 lectins bound to archaeal biofilms on pyrite and 21 lectins were binding to Acidianus sp. DSM 29099 biofilms on elemental sulfur; (ii) major binding patterns, e.g. tightly bound EPS and loosely bound EPS, were detected on both substrates; (iii) the three archaeal species produced various EPS glycoconjugates on pyrite surfaces. Additionally, the substratum induced different EPS glycoconjugates and biofilm structures of cells of Acidianus sp. DSM 29099. Our data provide new insights into interactions between acidophilic archaea on relevant surfaces and also indicate that FLBA is a valuable tool for in situ investigations on archaeal biofilms.
PMCID: PMC4408177  PMID: 25488256
7.  Local structure order in Pd78Cu6Si16 liquid 
Scientific Reports  2015;5:8277.
The short-range order (SRO) in Pd78Cu6Si16 liquid was studied by high energy x-ray diffraction and ab initio molecular dynamics (MD) simulations. The calculated pair correlation functions at different temperatures agree well with the experimental results. The partial pair correlation functions from ab intio MD simulations indicate that Si atoms prefer to be uniformly distributed while Cu atoms tend to aggregate. By performing structure analysis using Honeycutt-Andersen index, Voronoi tessellation, and atomic cluster alignment method, we show that the icosahedron and face-centered cubic SRO increase upon cooling. The dominant SRO is the Pd-centered Pd9Si2 motif, namely the structure of which motif is similar to the structure of Pd-centered clusters in the Pd9Si2 crystal. The study further confirms the existence of trigonal prism capped with three half-octahedra that is reported as a structural unit in Pd-based amorphous alloys. The majority of Cu-centered clusters are icosahedra, suggesting that the presence of Cu is benefit to promote the glass forming ability.
PMCID: PMC4317692  PMID: 25652079
8.  White Matter Integrity in Physically Fit Older Adults 
NeuroImage  2013;0:510-516.
White matter (WM) integrity declines with normal aging. Physical activity may attenuate age-related WM integrity changes and improve cognitive function. This study examined brain WM integrity in Masters athletes who have engaged in life-long aerobic exercise training. We tested the hypothesis that life-long aerobic training is associated with improved brain WM integrity in older adults.
Ten Masters athletes (3 females, age=72.2±5.3yrs, endurance training>15yrs) and 10 sedentary older adults similar in age and educational level (2 females, age=74.5±4.3yrs) participated. MRI fluid-attenuated-inversion-recovery (FLAIR) images were acquired to assess white matter hyper intensities (WMH) volume. Diffusion tensor imaging (DTI) was performed to evaluate the WM microstructural integrity with a DTI-derived metric, fractional anisotropy (FA) and mean diffusivity (MD).
After normalization to whole-brain volume, Masters athletes showed an 83% reduction in deep WMH volume relative to their sedentary counterparts (0.05 ± 0.05% vs. 0.29 ± 0.29%, p<0.05). In addition, we found an inverse relationship between aerobic fitness (VO2max) and deep WMH volume (r=−0.78, p<0.001). Using TBSS, Masters athletes showed higher FA values in the right superior corona radiata (SCR), both sides of superior longitudinal fasciculus (SLF), right inferior fronto-occipital fasciculus (IFO), and left inferior longitudinal fasciculus (ILF). In addition, Masters athletes also showed lower MD values in the left posterior thalamic radiation (PTR) and left cingulum hippocampus.
These findings suggest that life-long exercise is associated with reduced WMH and may preserve WM fiber microstructural integrity related to motor control and coordination in older adults.
PMCID: PMC3759589  PMID: 23769914
Aging; white matter disease; MRI; exercise; plasticity
9.  Model-based Quantification of Cerebral Hemodynamics as a Physiomarker for Alzheimer’s Disease? 
Annals of biomedical engineering  2013;41(11):2296-2317.
Previous studies have found that Alzheimer’s disease (AD) impairs cerebral vascular function, even at early stages of the disease. This offers the prospect of a useful diagnostic method for AD, if cerebral vascular dysfunction can be quantified reliably within practical clinical constraints. We present a recently developed methodology that utilizes a data-based dynamic nonlinear closed-loop model of cerebral hemodynamics to compute “physiomarkers” quantifying the state of cerebral flow autoregulation to pressure-changes (CA) and cerebral CO2 vasomotor reactivity (CVMR) in each subject. This model is estimated from beat-to-beat measurements of mean arterial blood pressure, mean cerebral blood flow velocity and end-tidal CO2, which can be made reliably and non-invasively under resting conditions. This model may also take an open-loop form and comparisons are made with the closed-loop counterpart. The proposed model-based physiomarkers take the form of two indices that quantify the gain of the CA and CVMR processes in each subject. It was found in an initial set of clinical data that the CVMR index delineates AD patients from control subjects and, therefore, may prove useful in the improved diagnosis of early-stage AD.
PMCID: PMC3992829  PMID: 23771298
Alzheimer’s disease; Physiomarkers; Modeling cerebral hemodynamics; Closed-loop modeling; Cerebral flow autoregulation; Cerebral vasomotor reactivity
10.  Neurodegenerative diseases in a dish: the promise of iPSC technology in disease modeling and therapeutic discovery 
Neurological Sciences  2014;36:21-27.
The study of stem-cell biology has been a flourishing research area because of its multi-differentiation potential. The emergence of induced pluripotent stem cells (iPSCs) open up the possibility of addressing obstructs, such as the limited cell source, inherent complexity of the human brain, and ethical constrains. Though still at its infancy phase, reprogramming of somatic cells has been demonstrating the ability to enhance in vitro study of neurodegenerative diseases and potential treatment. However, iPSCs would not thoroughly translate to the clinic before limitations are addressed. In this review, by summarizing the recent development of iPSC-based models, we will discuss the feasibility of iPSC technology on relevant diseases depth and illustrate how this new tool applies to drug screening and celluar therapy.
PMCID: PMC4282683  PMID: 25354658
Induced pluripotent stem cells; IPSCs; Neurodegenerative disease; Disease modeling; Drug screening; Cell therapy
11.  A high-content screening assay for small molecule modulators of oncogene-induced senescence 
Journal of biomolecular screening  2013;18(9):10.1177/1087057113491827.
Cellular senescence is a state of stable cell growth arrest. Activation of oncogenes such as RAS in mammalian cells typically triggers cellular senescence. Oncogene-induced senescence (OIS) is an important tumor suppression mechanism, and suppression of OIS contributes to cell transformation. Oncogenes trigger senescence through a multitude of incompletely understood downstream signaling events that frequently involve protein kinases. To identify target proteins required for RAS-induced senescence, we developed a small molecule screen in primary human fibroblasts undergoing senescence induced by oncogenic RAS (H-RasG12V). Using a high-content imaging system to monitor two hallmarks of senescence, senescence-associated β-galactosidase activity expression and inhibition of proliferation, we screened a library of known small molecule kinase inhibitors for those that suppressed OIS. Identified compounds were subsequently validated and confirmed using a third marker of senescence, senescence-associated heterochromatin foci. In summary, we have established a novel high-content screening platform that may be useful for elucidating signaling pathways mediating OIS by targeting critical pathway components.
PMCID: PMC3870888  PMID: 23733845
12.  New insight into the spin-conserving excitation of the negatively charged nitrogen-vacancy center in diamond 
Scientific Reports  2014;4:5144.
The negatively charged nitrogen-vacancy (N-V−) color center in diamond is an important solid-state single photon source for applications to quantum communication and distributed quantum computation. Its full usefulness relies on sufficient radiative emission of the optical photons which requires realizable control to enhance emission into the zero-phonon line (ZPL) but until now is still a challenge. Detailed understanding of the associated excitation process would be of essential importance for such objective. Here we report a theoretical work that probes the spin-conserving optical excitation of the N-V− center. Using density-functional-theory (DFT) calculations, we find that the ZPL and the phonon-side band (PSB) depend sensitively on the axial strain of the system. Besides, we find a relatively small PSB appearing at about 100 GPa in the emission spectrum at low temperatures, which provides a means to enhance the coherent emission of the N-V− center in quantum optical networks.
PMCID: PMC4042121  PMID: 24888367
13.  Closed-Loop Dynamic Modeling of Cerebral Hemodynamics 
Annals of biomedical engineering  2013;41(5):1029-1048.
The dynamics of cerebral hemodynamics have been studied extensively because of their fundamental physiological and clinical importance. In particular, the dynamic processes of cerebral flow autoregulation and CO2 vasomotor reactivity have attracted broad attention because of their involvement in a host of pathologies and clinical conditions (e.g. hypertension, syncope, stroke, traumatic brain injury, vascular dementia, Alzheimer’s disease, mild cognitive impairment etc.). This raises the prospect of useful diagnostic methods being developed on the basis of quantitative models of cerebral hemodynamics, if cerebral vascular dysfunction can be quantified reliably from data collected within practical clinical constraints. This paper presents a modeling method that utilizes beat-to-beat measurements of mean arterial blood pressure, cerebral blood flow velocity and end-tidal CO2 (collected non-invasively under resting conditions) to quantify the dynamics of cerebral flow autoregulation (CFA) and cerebral vasomotor reactivity (CVMR). The unique and novel aspect of this dynamic model is that it is nonlinear and operates in a closed-loop configuration.
PMCID: PMC3625507  PMID: 23292615
Cerebral Autoregulation; Nonlinear Modeling; Modeling Cerebral Hemodynamics; Closed-Loop Modeling; Cerebral Flow Autoregulation; Cerebral Vasomotor Reactivity
15.  FoxO mediates APP-induced AICD-dependent cell death 
Wang, X | Wang, Z | Chen, Y | Huang, X | Hu, Y | Zhang, R | Ho, M S | Xue, L
Cell Death & Disease  2014;5(5):e1233-.
The amyloid precursor protein (APP) is a broadly expressed transmembrane protein that has a significant role in the pathogenesis of Alzheimer's disease (AD). APP can be cleaved at multiple sites to generate a series of fragments including the amyloid β (Aβ) peptides and APP intracellular domain (AICD). Although Aβ peptides have been proposed to be the main cause of AD pathogenesis, the role of AICD has been underappreciated. Here we report that APP induces AICD-dependent cell death in Drosophila neuronal and non-neuronal tissues. Our genetic screen identified the transcription factor forkhead box O (FoxO) as a crucial downstream mediator of APP-induced cell death and locomotion defect. In mammalian cells, AICD physically interacts with FoxO in the cytoplasm, translocates with FoxO into the nucleus upon oxidative stress, and promotes FoxO-induced transcription of pro-apoptotic gene Bim. These data demonstrate that APP modulates FoxO-mediated cell death through AICD, which acts as a transcriptional co-activator of FoxO.
PMCID: PMC4047897  PMID: 24832605
app; AICD; alzheimer's disease; foxo
16.  TXNL1-XRCC1 pathway regulates cisplatin-induced cell death and contributes to resistance in human gastric cancer 
Xu, W | Wang, S | Chen, Q | Zhang, Y | Ni, P | Wu, X | Zhang, J | Qiang, F | Li, A | Røe, O D | Xu, S | Wang, M | Zhang, R | Zhou, J
Cell Death & Disease  2014;5(2):e1055-.
Cisplatin is a cytotoxic platinum compound that triggers DNA crosslinking induced cell death, and is one of the reference drugs used in the treatment of several types of human cancers including gastric cancer. However, intrinsic or acquired drug resistance to cisplatin is very common, and leading to treatment failure. We have recently shown that reduced expression of base excision repair protein XRCC1 (X-ray repair cross complementing group1) in gastric cancerous tissues correlates with a significant survival benefit from adjuvant first-line platinum-based chemotherapy. In this study, we demonstrated the role of XRCC1 in repair of cisplatin-induced DNA lesions and acquired cisplatin resistance in gastric cancer by using cisplatin-sensitive gastric cancer cell lines BGC823 and the cisplatin-resistant gastric cancer cell lines BGC823/cis-diamminedichloridoplatinum(II) (DDP). Our results indicated that the protein expression of XRCC1 was significantly increased in cisplatin-resistant cells and independently contributed to cisplatin resistance. Irinotecan, another chemotherapeutic agent to induce DNA damaging used to treat patients with advanced gastric cancer that progressed on cisplatin, was found to inhibit the expression of XRCC1 effectively, and leading to an increase in the sensitivity of resistant cells to cisplatin. Our proteomic studies further identified a cofactor of 26S proteasome, the thioredoxin-like protein 1 (TXNL1) that downregulated XRCC1 in BGC823/DDP cells via the ubiquitin-proteasome pathway. In conclusion, the TXNL1-XRCC1 is a novel regulatory pathway that has an independent role in cisplatin resistance, indicating a putative drug target for reversing cisplatin resistance in gastric cancer.
PMCID: PMC3944244  PMID: 24525731
cisplatin; gastric cancer; drug resistance; XRCC1; TXNL1
17.  ChIP-seq analysis of histone H3K9 trimethylation in peripheral blood mononuclear cells of membranous nephropathy patients 
Membranous nephropathy (MN), characterized by the presence of diffuse thickening of the glomerular basement membrane and subepithelial in situ immune complex disposition, is the most common cause of idiopathic nephrotic syndrome in adults, with an incidence of 5-10 per million per year. A number of studies have confirmed the relevance of several experimental insights to the pathogenesis of human MN, but the specific biomarkers of MN have not been fully elucidated. As a result, our knowledge of the alterations in histone methylation in MN is unclear. We used chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq) to analyze the variations in a methylated histone (H3K9me3) in peripheral blood mononuclear cells from 10 MN patients and 10 healthy subjects. There were 108 genes with significantly different expression in the MN patients compared with the normal controls. In MN patients, significantly increased activity was seen in 75 H3K9me3 genes, and decreased activity was seen in 33, compared with healthy subjects. Five positive genes, DiGeorge syndrome critical region gene 6 (DGCR6), sorting nexin 16 (SNX16), contactin 4 (CNTN4), baculoviral IAP repeat containing 3 (BIRC3), and baculoviral IAP repeat containing 2 (BIRC2), were selected and quantified. There were alterations of H3K9me3 in MN patients. These may be candidates to help explain pathogenesis in MN patients. Such novel findings show that H3K9me3 may be a potential biomarker or promising target for epigenetic-based MN therapies.
PMCID: PMC3932972  PMID: 24345872
ChIP-seq; Epigenetics; H3K9me3; Membranous nephropathy
18.  Functional analyses of the mutation nt-128 T→G in the hepatocyte nuclear factor-1α promoter region in Chinese diabetes pedigrees 
Hepatocyte nuclear factor-1α (HNF-1α) regulates the expression of genes encoding proteins involved in glucose metabolism and insulin secretion. Mutations in the HNF-1α gene cause maturity-onset diabetes of the young Type 3. However, the mechanism leading to this disease has not been completely ascertained. Previously, we found a novel mutation in the regulatory element of the human HNF-1α gene in two Chinese diabetes pedigrees. The nucleotide at position -128 T was substituted by G (nt-128 T→G). In this study, we analysed the functional defect of nt-128 T→G in HNF-1α transcription activity.
Luciferase reporter gene assays were carried out to examine the functional characteristics of this mutant. Electrophoretic mobility shift assays and chromatin immunoprecipitation were performed to confirm the binding of nuclear proteins to oligonucleotides.
The variant construct (nt-128 T→G) had a 1.65-fold increase in promoter activity compared with that of the wild-type construct in HepG2 cells and a 1.33-fold increase in MIN6 cells, respectively. The variant resided at a FOXA/ HNF-3 binding site identified by a series of competitive electrophoretic mobility shift assays and antibody supershift analyses. The assays showed a differential binding affinity in the wild-type and the nt-128 T→G mutant fragments by FOXA/ HNF-3. Chromatin immunoprecipitation indicated that FOXA/ HNF-3 bound to this region in vivo. One nucleotide substitution in the FOXA/ HNF-3 site in the human HNF-1α regulatory element caused an increase of HNF-1α transcriptional activity.
Our data suggested that this substitution in the promoter region affects DNA–protein interaction and HNF-1α gene transcription. The mutant may contribute to the development of diabetes in these two nt-128 T→G pedigrees of Chinese.
PMCID: PMC3570122  PMID: 22413961
19.  Impact of a Prototype Visualization Tool for New Information in EHR Clinical Documents 
Applied Clinical Informatics  2012;3(4):404-418.
EHR clinical document synthesis by clinicians may be time-consuming and error-prone due to the complex organization of narratives, excessive redundancy within documents, and, at times, inadvertent proliferation of data inconsistencies. Development of EHR systems that are easily adaptable to the user’s work processes requires research into visualization techniques that can optimize information synthesis at the point of care.
To evaluate the effect of a prototype visualization tool for clinically relevant new information on clinicians’ synthesis of EHR clinical documents and to understand how the tool may support future designs of clinical document user interfaces.
A mixed methods approach to analyze the impact of the visualization tool was used with a sample of eight medical interns as they synthesized EHR clinical documents to accomplish a set of four pre-formed clinical scenarios using a think-aloud protocol.
Differences in the missing (unretrieved) patient information (2.3±1.2 [with the visualization tool] vs. 6.8±1.2 [without the visualization tool], p = 0.08) and accurate inferences (1.3±0.3 vs 2.3±0.3, p = 0.09) were not statistically significant but suggest some improvement with the new information visualization tool. Despite the non-significant difference in total times to task completion (43±4 mins vs 36±4 mins, p = 0.35) we observed shorter times for two scenarios with the visualization tool, suggesting that the time-saving benefits may be more evident with certain clinical processes. Other observed effects of the tool include more intuitive navigation between patient details and increased efforts towards methodical synthesis of clinical documents.
Our study provides some evidence that new information visualization in clinical notes may positively influence synthesis of patient information from EHR clinical documents. Our findings provide groundwork towards a more effective display of EHR clinical documents using advanced visualization applications.
PMCID: PMC3613039  PMID: 23646087
Electronic health records; data visualization; interfaces and usability
20.  Discontinuous properties of current-induced magnetic domain wall depinning 
Scientific Reports  2013;3:3080.
The current-induced motion of magnetic domain walls (DWs) confined to nanostructures is of great interest for fundamental studies as well as for technological applications in spintronic devices. Here, we present magnetic images showing the depinning properties of pulse-current-driven domain walls in well-shaped Permalloy nanowires obtained using photoemission electron microscopy combined with x-ray magnetic circular dichroism. In the vicinity of the threshold current density (Jth = 4.2 × 1011 A.m−2) for the DW motion, discontinuous DW depinning and motion have been observed as a sequence of “Barkhausen jumps”. A one-dimensional analytical model with a piecewise parabolic pinning potential has been introduced to reproduce the DW hopping between two nearest neighbour sites, which reveals the dynamical nature of the current-driven DW motion in the depinning regime.
PMCID: PMC3812652  PMID: 24170087
21.  Electroacupuncture inhibition of hyperalgesia in an inflammatory pain rat model: involvement of distinct spinal serotonin and norepinephrine receptor subtypes 
BJA: British Journal of Anaesthesia  2012;109(2):245-252.
Although acupuncture analgesia is well documented, its mechanisms have not been thoroughly clarified. We previously showed that electroacupuncture (EA) activates supraspinal serotonin- and norepinephrine-containing neurones that project to the spinal cord. This study investigates the involvement of spinal alpha(2)-adrenoceptors (α2-ARs) and 5-hydroxytryptamine (serotonin) receptors (5-HTRs) in EA effects on an inflammatory pain rat model.
Inflammatory hyperalgesia was induced by injecting complete Freund's adjuvant (CFA, 0.08 ml) into the plantar surface of one hind paw and assessed by paw withdrawal latency (PWL) to a noxious thermal stimulus. The selective α2a-AR antagonist BRL-44408, α2b-AR antagonist imiloxan hydrochloride, 5-HT2B receptor (5-HT2BR) antagonist SB204741, 5-HT3R antagonist LY278584, or 5-HT1AR antagonists NAN-190 hydrobromide, or WAY-100635 were intrathecally administered 20 min before EA or sham EA, which was given 2 h post-CFA at acupoint GB30.
EA significantly increased PWL compared with sham [7.20 (0.46) vs 5.20 (0.43) s]. Pretreatment with α2a-AR [5.35 (0.45) s] or 5-HT1AR [5.22 (0.38) s] antagonists blocked EA-produced anti-hyperalgesia; α2b-AR, 5-HT2BR, and 5-HT3R antagonist pretreatment did not. Sham plus these antagonists did not significantly change PWL compared with sham plus vehicle, indicating that the antagonists had little effect on PWL. Immunohistochemical staining demonstrated that α2a-ARs are on primary afferents and 5-HT1ARs are localized in N-methyl-d-aspartic acid (NMDA) subunit NR1-containing neurones in the spinal dorsal horn.
The data show that α2a-ARs and 5-HT1ARs are involved in the EA inhibition of inflammatory pain and that the NMDA receptors are involved in EA action.
PMCID: PMC3393079  PMID: 22628394
acupuncture; norepinephrine; pain; serotonin; spinal cord
22.  Genome-wide association study in a Chinese population identifies a susceptibility locus for type 2 diabetes at 7q32 near PAX4 
Diabetologia  2013;56(6):1291-1305.
Most genetic variants identified for type 2 diabetes have been discovered in European populations. We performed genome-wide association studies (GWAS) in a Chinese population with the aim of identifying novel variants for type 2 diabetes in Asians.
We performed a meta-analysis of three GWAS comprising 684 patients with type 2 diabetes and 955 controls of Southern Han Chinese descent. We followed up the top signals in two independent Southern Han Chinese cohorts (totalling 10,383 cases and 6,974 controls), and performed in silico replication in multiple populations.
We identified CDKN2A/B and four novel type 2 diabetes association signals with p < 1 × 10−5 from the meta-analysis. Thirteen variants within these four loci were followed up in two independent Chinese cohorts, and rs10229583 at 7q32 was found to be associated with type 2 diabetes in a combined analysis of 11,067 cases and 7,929 controls (pmeta = 2.6 × 10−8; OR [95% CI] 1.18 [1.11, 1.25]). In silico replication revealed consistent associations across multiethnic groups, including five East Asian populations (pmeta = 2.3 × 10−10) and a population of European descent (p = 8.6 × 10−3). The rs10229583 risk variant was associated with elevated fasting plasma glucose, impaired beta cell function in controls, and an earlier age at diagnosis for the cases. The novel variant lies within an islet-selective cluster of open regulatory elements. There was significant heterogeneity of effect between Han Chinese and individuals of European descent, Malaysians and Indians.
Our study identifies rs10229583 near PAX4 as a novel locus for type 2 diabetes in Chinese and other populations and provides new insights into the pathogenesis of type 2 diabetes.
Electronic supplementary material
The online version of this article (doi:10.1007/s00125-013-2874-4) contains peer-reviewed but unedited supplementary material, which is available to authorised users.
PMCID: PMC3648687  PMID: 23532257
Chinese; Diabetes; East Asians; Genetics; Genome-wide association study
24.  Overexpression of Uromodulin-like1 accelerates follicle depletion and subsequent ovarian degeneration 
Cell Death & Disease  2012;3(11):e433-.
Murine Uromodulin-like 1 (Umodl1) encodes Ca2+-dependent EGF-like membrane-bound proteins. This study presents its novel expression in the immune and female reproductive systems. Upon stimulation by CD3/CD28 antibodies, Umodl1 showed a prompt and robust response in the proliferating CD4+ T cells, suggesting its implication in immune defense against pathogens. In ovary, Umodl1 is regulated by gonadotropins. Mice carrying extra copies of functional Umodl1 were generated by BAC transgenesis. Defects in the female reproductive system became evident from 4 months of age, manifested by reduced or diminished fertility. Histology revealed that the ovaries contained very few discernible follicles in the cortical region, and were devoid of distinguishable corpus lutea (CL). Among the multilayered preantral follicles, elevated apoptosis was observed in both the oocytes and surrounding granulosa cells (GCs). Furthermore, a high level of PPARγ indicated an abnormal adipogenesis in the mutant ovaries, which resulted in the conversion of GCs into adipocytes. By 6 months of age, all mutant mice became anovulatory. Ovarian tissues including CL, follicles of various stages and associated stromal cells were degenerated. Altered expression of AMH, follicle-stimulating hormone and other ovary-specific marker genes such as Gdf-9, Rnf35, NOHLH and Gcx-1 further demonstrated that the molecular properties of the mutant ovaries have been severely disturbed. This work presents a novel animal model for investigating the pathogenesis of premature ovarian failure or early ovarian ageing.
PMCID: PMC3542605  PMID: 23190605
uromodulin-like 1; BAC transgenesis; ovarian follicle; oocyte; premature ovarian failure; gain-of-function
25.  Effects on subjective and objective alertness and sleep in response to evening light exposure in older subjects 
Behavioural brain research  2011;224(2):272-278.
Evening bright light exposure is reported to ameliorate daytime sleepiness and age-related sleep complaints, and also delays the timing of circadian rhythms. We tested whether evening light exposure given to older adults with sleep-wake complaints would delay the timing of their circadian rhythms with respect to their sleep timing, thereby reducing evening sleepiness and improving subsequent sleep quality. We examined the impact of evening light exposure from two different light sources on subjective alertness, EEG activity during wakefulness, and sleep stages.
Ten healthy older adults with sleep complaints (mean age=63.3 yrs; 6F) participated in a 13-day study. After three baseline days, circadian phase was assessed. On the evening of days 5–8 the subjects were exposed for 2 h to either polychromatic blue-enriched white light or standard white fluorescent light, and on the following day circadian phase was re-assessed. Subjects were allowed to leave the laboratory during all but the two days when the circadian phase assessment took place. Evening assessments of subjective alertness, and wake and sleep EEG data were analyzed.
Subjective alertness and wake EEG activity in the alpha range (9.75–11.25 Hz) were significantly higher during light exposures when compared to the pre-light exposure evening (p<0.05). The light exposures produced circadian phase shifts and significantly prolonged latency to rapid eye-movement (REM) sleep for both light groups (p<0.05). The increase in wake EEG alpha activity during the light exposures was negatively correlated with REM sleep duration (p<0.05).
Evening light exposure could benefit older adults with early evening sleepiness, without negatively impacting the subsequent sleep episode.
PMCID: PMC3169848  PMID: 21664380
sleep; circadian; aging; light exposure

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