Entropic comparison of Landau-Zener and Demkov interactions in the phase space of a quadrupole billiard.

We investigate two types of avoided crossings in a chaotic billiard within the framework of information theory. The Shannon entropy in the phase space for the Landau-Zener interaction increases as the center of the avoided crossing is approached, whereas for the Demkov interaction, the Shannon entropy decreases as the center of avoided crossing is passed by with an increase in the deformation parameter. This feature can provide a new indicator for scar formation. In addition, it is found that the Fisher information of the Landau-Zener interaction is significantly larger than that of the Demkov interaction.

Donepezil 23 mg in Asian patients with moderate-to-severe Alzheimer's disease.

BACKGROUND: Ethnic diversity between different populations may affect treatment safety and efficacy. AIMS AND METHODS: A subanalysis to a global trial (study 326) was carried out to ascertain the safety and efficacy of donepezil 23 mg/day compared with donepezil 10 mg/day in Asian patients with moderate-to-severe Alzheimer's disease. Changes in cognition and global functioning were measured by the Severe Impairment Battery (SIB) and Clinician's Interview-Based Impression of Change Plus Caregiver Input (CIBIC-Plus), respectively, at week 24. RESULTS: Cognitive improvement measured by SIB score was greater with donepezil 23 mg than with donepezil 10 mg (+1.36 vs -1.56]; difference, 2.92). There was no difference between the groups in global function measured by the CIBIC-Plus (3.94 and 3.95, respectively). Overall, 119 patients (82.1%) receiving donepezil 23 mg and 56 (71.8%) receiving donepezil 10 mg experienced ≥1 treatment emergent adverse events (TEAEs). In the donepezil 23 mg group, the incidence of TEAEs was higher among patients of lower weight (<55 kg) at baseline than in those of higher weight (64 of 75 patients [85.3%] vs 55 of 70 patients [78.5%]). CONCLUSIONS: The benefits and risks associated with donepezil 23 mg in Asian patients are comparable to those of the global study population.

Inhibition of microRNA-449a prevents IL-1ß-induced cartilage destruction via SIRT1.

OBJECTIVE: SIRT1 has anti-inflammatory as well as protective effects in chondrocytes. The object of this study was to investigate whether microRNA-449a regulates expression of SIRT1, which inhibits expression of catabolic genes in IL-1ß-induced cartilage destruction. MATERIALS AND METHODS: MicroRNA-449a expression was determined in OA chondrocytes and IL-1ß-induced chondrocytes by real-time PCR. MicroRNA-449a binding sites on the 3'-UTR of SIRT1 mRNA and binding site conservation were examined using microRNA target prediction tools. SIRT1-overexpressing or knockdown chondrocytes were transfected with microRNA-449a or anti-microRNA-449a mimic and stimulated by IL-1ß. Expression of catabolic and anabolic genes was examined by real-time PCR and western blotting. Finally, positive effects of anti-microRNA-449a on expression of these genes were confirmed by western analysis of OA chondrocytes. RESULTS: Expression of microRNA-449a was increased in OA chondrocytes and IL-1ß-induced chondrocytes. MMP-13 expression was enhanced, whereas type II collagen and SIRT1 expression were decreased in IL-1ß-induced chondrocytes. SIRT1 overexpression resulted in decreased expression of catabolic genes such as MMPs and ADAMTSs in response to IL-1ß, but these effects were moderated by microRNA-449a. Suppression of microRNA-449a by anti-microRNA-449a inhibited expression of catabolic genes despite IL-1ß stimulation, but these effects were abolished in SIRT1 knockdown chondrocytes. Furthermore, expression of catabolic genes was decreased and expression of type II collagen as well as SIRT1 was restored by anti-microRNA-449a in OA chondrocytes as well as in IL-1ß-induced chondrocytes. CONCLUSION: Silencing of microRNA-449a had a protective effect, inhibiting catabolic gene expression and restoring anabolic gene expression, by targeting SIRT1 in IL-1ß-induced cartilage destruction.

Generation of RUNX3 knockout pigs using CRISPR/Cas9-mediated gene targeting.

Pigs are an attractive animal model to study the progression of cancer because of their anatomical and physiological similarities to human. However, the use of pig models for cancer research has been limited by availability of genetically engineered pigs which can recapitulate human cancer progression. Utilizing genome editing technologies such as CRISPR/Cas9 system allows us to generate genetically engineered pigs at a higher efficiency. In this study, specific CRISPR/Cas9 systems were used to target RUNX3, a known tumour suppressor gene, to generate a pig model that can induce gastric cancer in human. First, RUNX3 knockout cell lines carrying genetic modification (monoallelic or biallelic) of RUNX3 were generated by introducing engineered CRISPR/Cas9 system specific to RUNX3 into foetal fibroblast cells. Then, the genetically modified foetal fibroblast cells were used as donor cells for somatic cell nuclear transfer, followed by embryo transfer. We successfully obtained four live RUNX3 knockout piglets from two surrogates. The piglets showed the lack of RUNX3 protein in their internal organ system. Our results demonstrate that the CRISPR/Cas9 system is effective in inducing mutations on a specific locus of genome and the RUNX3 knockout pigs can be useful resources for human cancer research and to develop novel cancer therapies.

Cross-sectional scanning thermal microscopy of ErAs/GaAs superlattices grown by molecular beam epitaxy.

Scanning thermal microscopy has been implemented in a cross-sectional geometry, and its application for quantitative, nanoscale analysis of thermal conductivity is demonstrated in studies of an ErAs/GaAs nanocomposite superlattice. Spurious measurement effects, attributable to local thermal transport through air, were observed near large step edges, but could be eliminated by thermocompression bonding to an additional structure. Using this approach, bonding of an ErAs/GaAs superlattice grown on GaAs to a silicon-on-insulator wafer enabled thermal signals to be obtained simultaneously from Si, SiO2, GaAs, and ErAs/GaAs superlattice. When combined with numerical modeling, the thermal conductivity of the ErAs/GaAs superlattice measured using this approach was 11 ± 4 W m(-1) K(-1).

Donepezil across the spectrum of Alzheimer's disease: dose optimization and clinical relevance.

Alzheimer's disease (AD) is an irreversible and progressive neurodegenerative disorder. AD is the most common cause of dementia worldwide, and its incidence is increasing in line with population aging. The primary feature of AD is progressive cognitive decline, and severe AD is characterized by reduced communication skills and mobility. However, successful treatment can substantially improve quality of life. Donepezil is an acetylcholinesterase inhibitor approved for use across the full spectrum of mild, moderate, and severe AD. Donepezil has been available at doses of 5 or 10 mg once daily for more than a decade and, more recently, a single high once-daily sustained-release 23-mg dose has been approved for treatment of patients with moderate to severe AD. The rationale for the higher dose formulation was the expected increase in acetylcholinesterase inhibition given the dose-response relationship of donepezil, with the benefits of the higher dose being most apparent in patients with more advanced AD. Donepezil 5 and 10 mg/day have been well studied in mild-to-moderate AD, and a clinical trial has confirmed the benefits of donepezil 23 mg/day in patients with moderate to severe AD, particularly for language and visuospatial ability. This review presents an overview of the evidence for donepezil across the spectrum of AD, with a focus on dose optimization for disease progression.

Inhibition of adipogenesis in 3T3-L1 cells and suppression of abdominal fat accumulation in high-fat diet-feeding C57BL/6J mice after downregulation of hyaluronic acid.

OBJECTIVE: Adipogenesis can be spatially and temporally regulated by extracellular matrix (ECM). We hypothesized that the regulation of hyaluronic acid (HA), a component of the ECM, can affect adipogenesis in fat cells. The effects of HA on adipogenesis were investigated in vitro in 3T3-L1 cells and in vivo in high-fat diet-feeding C57BL/6J mice. METHODS: We investigated the effects of HA by degradation of pre-existing or synthesized HA and artificial inhibition of HA synthesis in adipogenesis. RESULTS: In vitro adipogenesis in 3T3-L1 cells was inhibited by treating them with exogenous hyaluronidase (HYAL) and with 4-methylumbelliferone, which inhibited the synthesis of HA in a concentration-dependent manner. In vivo, abdominal fat accumulation in high-fat diet-feeding C57BL/6J mice was suppressed by exogenous HYAL 10(4) IU injections, which was associated with reduction of lipid accumulation in liver and increase of insulin sensitivity. CONCLUSION: Changes in the ECM such as accumulation of high molecular weight of HA by HAS and degradation of HA by endogenous HYAL were essential for adipogenesis both in vitro and in vivo.

Hiccup-like segmental myoclonus in thoracic compressive myelopathy: a case report.

STUDY DESIGN: A case report. OBJECTIVES: This study discusses a case of spinal segmental myoclonus caused by thoracic myelopathy, mimicking hiccup spasms. Spinal myoclonus caused by thoracic myelopathy is extremely rare. It can be misdiagnosed as chronic intractable hiccups due to similar clinical manifestations. SETTING: Korea University Anam Hospital, Seoul, Republic of Korea. METHODS: A 42-year-old man presented with a history of involuntary jerky movement of the upper abdominal wall muscles that had been continuing for over 3 years. A neurological examination, brain computed tomography and electroencephalogram did not reveal a cause of the symptoms. Electromyography was performed on the abdominal muscles and the findings revealed were compatible with spinal myoclonus. The spinal myoclonus had started in the abdominal muscles, with a spinal magnetic resonance imaging revealing a disc protrusion compressing the anterior spinal cord. RESULTS: The cause of the spinal myoclonus was determined to be spinal myelopathy due to mild T7 disc protrusion. The patient refused surgical or invasive interventions and was conservatively treated with clonazepam. The symptoms were reported to be less frequent following the treatment. CONCLUSION: Compressive myelopathy developed from disc protrusion may cause spinal myoclonus mimicking as hiccup spasms.

Extranodal natural killer/T-cell lymphoma from skin or soft tissue: suggestion of treatment from multinational retrospective analysis.

BACKGROUND: Clinical features and outcomes of extranodal natural killer/T-cell lymphoma (ENKL) arising from extranasal sites are not fully understood. The purpose of this study was to study the prognosis and treatment outcome of skin/soft tissue primary ENKL. PATIENTS AND METHODS: This multicenter retrospective study included 48 patients with skin/soft tissue primary ENKL diagnosed from 1993 to 2010. RESULTS: Patients with Ann Arbor stage I, T1-2N0M0 by International Society for Cutaneous Lymphomas-European Organization of Research and Treatment of Cancer TNM (tumour-node-metastasis) stage, International prognostic index score of 0-1, and a Korean prognostic index (KPI) score of 0-1 were associated with better survival. Four of five patients with T1-2N0M0 disease achieved complete response with radiation alone. In disseminated disease, only 6 of 13 patients responded to anthracycline-containing chemotherapy, and all the two patients receiving SMILE showed response. CONCLUSION: In conclusion, we identified the prognostic value of KPI, and we suggest a treatment recommendation according to the TNM (tumour-node-metastasis) stage. Radiotherapy with/without chemotherapy seemed to be optimal in localized disease. In advanced stages, a more aggressive treatment regimen with newer agents should be sought.

Effect of temperature on optical and electronic properties of InGaP/InGaAIP multiple quantum wells.

The optical and electronic properties in an InGaP/InGaAIP multiple quantum well (MQW) grown by using molecular-beam epitaxy utilizing the digital alloy technique were investigated through temperature-dependent photoluminescence (PL) measurements and numerical calculations. The high-resolution transmission electron microscopy images showed that the sample clearly displayed the InGaP wells and the InGaAIP barriers and separate confinement heterostructure layers. The PL measurements at various temperatures were performed to investigate the interband transitions of the InGaP/InGaAIP MQW. The electronic subband energies and the wavefunctions in the InGaP/InGaAIP MQW at several temperatures were determined by using a finite element method employing the standard 8-band k x p Lagrangian. The numerical results for optical interband transition energies from the ground state electron subband to the ground state heavy-hole subband of the InGaP/InGaAIP MQW at various temperatures were in reasonable agreement with the excitonic transition energies observed in the PL measurements.

Effect of Total Mixed Ration with Fermented Feed on Ruminal In vitro Fermentation, Growth Performance and Blood Characteristics of Hanwoo Steers.

In this study, two experiments were conducted to evaluate the total mixed ration with fermented feed (TMRF) and total mixed ration (TMR) by rumen in vitro fermentation and their effects on the growth performance and blood characteristics of Hanwoo steers. In experiment 1, three Hanwoo steers (600±47 kg), each permanently fitted with a ruminal cannula were used. In this experiment, three diets designated as T1, TMRF (18.4% fermented feed, tall fescue, mammoth wild rye forage and whole crop barley); T2, TMRF (17.7% fermented feed, rice straw and whole crop barley); and T3, TMR (rice straw, whole crop barley and probiotics, but no fermented feed), which were subjected to rumen in vitro fermentation for 48 h. The results demonstrated that DM disappearance rate gradually increased with advancing fermentation time, but T1 and T2 were higher than the T3 (p<0.05) from 3 h to 12 h, but insignificant (p>0.05) at 24 and 48 h. None of the specific VFAs were affected except for acetic and non volatile lactic acids, which were produced more in T2 than in T1 and T3 at 24 h and 48 h of incubation. A/P was lower in T1 and T2 than inT3 at 24 h (p<0.05) and 48 h (p>0.05) of incubation. These results confirmed that TMRF-related treatment shows a superior performance to that of TMR during the ruminal fermentation period. In experiment 2, the three diets in experiment 1 plus 1 more control diet (concentrates, probiotics and 2% rice straw of body weight) were fed to the 48 Hanwoo steers (160±10 kg) for a period of 168 d. The results demonstrated that the daily and total live weight gain and feed efficiency were higher (p<0.05) in the TMRF and TMR groups than in the control group. SGOT, SGPT and BUN (p<0.05) were reduced in TMRF relative to the control and TMR groups by 168 d which confirmed that TMRF shows better blood profiles than the TMR and control groups. Overall, these results appear to show that TMRF has better in vitro ruminal characteristics than those of TMR; growth performance and blood profiles were also found to be superior in TMRF than in the TMR and control groups. Thus, our findings suggest that TMRF-based feed supplies are favorable for Hanwoo cattle.

Risk of hemorrhagic gastropathy associated with colonoscopy bowel preparation using oral sodium phosphate solution.

BACKGROUND AND STUDY AIMS: Oral sodium phosphate (NaP) solution is widely used for colonoscopy bowel preparation and it may cause aphthous ulcers in the colon. Our aim was to evaluate whether oral NaP solution is associated with gastric mucosal lesions. METHODS: A total of 20 070 individuals underwent esophagogastroduodenoscopy (EGD) with colonoscopy, and 4271 individuals underwent EGD without colonoscopy, for cancer screening. Oral NaP solutions were used for bowel preparation prior to colonoscopy. Hemorrhagic gastropathy was graded using a five-point scale for erosive mucosal injury. The effect of NaP bowel preparation on hemorrhagic gastropathy was estimated using multiple logistic regression analysis with odds ratios (ORs) and 95 % confidence intervals (CIs). RESULTS: The incidence of hemorrhagic gastropathy was 1.6 % (70/4271) in the EGD only group and 4.0 % (809/20 070) in the EGD with colonoscopy group ( P < 0.001, unadjusted OR 2.55, 95 %CI 1.99 - 3.27). The ORs for mild (grade 1 - 2), moderate (grade 3), and severe (grade 4) hemorrhagic gastropathy according to NaP use were 1.92 (95 %CI 1.45 - 2.54), 4.72 (95 %CI 2.65 - 8.47), and 5.99 (95 %CI 1.46 - 24.63), respectively. After adjustment for confounding factors, NaP solution was a significant risk factor for acute hemorrhagic gastropathy in the multivariate analysis (OR 1.92, 95 %CI 1.34-2.74). In addition, male sex, a body mass index (kg/m (2)) of less than 20, concurrent use of antihypertensive or nonsteroidal anti-inflammatory drugs, and duodenal ulcers were independently associated with the development of hemorrhagic gastropathy. HELICOBACTER PYLORI infection and atrophic gastritis were negatively associated with hemorrhagic gastropathy. CONCLUSION: Oral NaP bowel preparation for colonoscopy was associated with hemorrhagic gastropathy.

Interictal metabolic changes in episodic migraine: a voxel-based FDG-PET study.

Whereas there are many H(2)(15)O-positron emission tomography (PET) studies demonstrating neuronal activation during acute migraine attacks, little information is available on the interictal (headache-free period) glucose metabolic changes in migraine. We therefore conducted voxel-based statistical parametric mapping analysis of (18)F-fluorodeoxyglucose-PET to evaluate interictal metabolic differences between 20 episodic migraine patients (four with aura; three men; mean age 34.0 +/- 6.4 years) and 20 control subjects. Separate correlation analyses were performed to delineate a possible relationship between regional glucose metabolism and disease duration or lifetime headache frequency in migraine patients. Group comparison showed that migraine patients had significant hypometabolism in several regions known to be involved in central pain processing, such as bilateral insula, bilateral anterior and posterior cingulate cortex, left premotor and prefrontal cortex, and left primary somatosensory cortex (uncorrected P < 0.001, corrected P < 0.05 with small volume corrections). Correlation analyses showed that regional metabolism of the insula and anterior cingulate cortex had significant negative correlations with disease duration and lifetime headache frequency (uncorrected P < 0.001, corrected P < 0.05 with small volume corrections). Our findings of progressive glucose hypometabolism in relation to increasing disease duration and increasing headache frequency suggest that repeated migraine attacks over time lead to metabolic abnormalities of selective brain regions belonging to the central pain matrix.

Radiomics Study of Thyroid Ultrasound for Predicting BRAF Mutation in Papillary Thyroid Carcinoma: Preliminary Results.

BACKGROUND AND PURPOSE: It is not known how radiomics using ultrasound images contribute to the detection of BRAF mutation. This study aimed to evaluate whether a radiomics study of gray-scale ultrasound can predict the presence or absence of B-Raf proto-oncogene, serine/threonine kinase (BRAF) mutation in papillary thyroid cancer. MATERIALS AND METHODS: The study retrospectively included 96 thyroid nodules that were surgically confirmed papillary thyroid cancers between January 2012 and June 2013. BRAF mutation was positive in 48 nodules and negative in 48 nodules. For analysis, ROIs from the nodules were demarcated manually on both longitudinal and transverse sonographic images. We extracted a total of 86 radiomics features derived from histogram parameters, gray-level co-occurrence matrix, intensity size zone matrix, and shape features. These features were used to build 3 different classifier models, including logistic regression, support vector machine, and random forest using 5-fold cross-validation. The performance including accuracy, sensitivity, specificity, positive predictive value, negative predictive value, and area under the receiver operating characteristic curve, of the different models was evaluated. RESULTS: The incidence of high-suspicion nodules diagnosed on ultrasound was higher in the BRAF mutation-positive group than in the mutation-negative group (P = .004). The radiomics approach demonstrated that all classification models showed moderate performance for predicting the presence of BRAF mutation in papillary thyroid cancers with an area under the curve value of 0.651, accuracy of 64.3%, sensitivity of 66.8%, and specificity of 61.8%, on average, for the 3 models. CONCLUSIONS: Radiomics study using thyroid sonography is limited in predicting the BRAF mutation status of papillary thyroid carcinoma. Further studies will be needed to validate our results using various diagnostic methods.

Usefulness of a photophobia questionnaire in patients with migraine.

Photophobia is an important criterion for the diagnosis of migraine. However, several Asian epidemiological surveys about migraine have shown lesser prevalence of photophobia than that of Western studies. This discrepancy is probably caused by underestimation of photophobia due to inappropriate questioning of patients by physicians. To investigate this issue, we developed a questionnaire about photophobia and evaluated its usefulness in 103 patients with migraine. In phase 1 of the study, we found good repeatability of the questionnaire with a 0.826 kappa coefficient. In phase 2, the prevalence of photophobia from interviews and that from the questionnaire were compared. The prevalence of interview-documented photophobia was 51.5% and of questionnaire-documented photophobia 82.5% (P < 0.001). In phase 3, we attempted to make a short-form questionnaire with the same detection power of the questionnaire study. Two short-form questionnaires were identified as a useful method for detecting photophobia. The prevalence of photophobia could be underreported via interview, especially in Asian migraineurs. Using this questionnaire to test for photophobia, the diagnostic rate of photophobia and migraine could be improved.

The relationship of pain and health-related quality of life in Korean patients with Parkinson's disease.

BACKGROUND: Parkinson's disease (PD) is a chronic progressive neurodegenerative disorder. Increasing attention has been focused on the pain and health-related quality of life (HrQOL) in patients with PD. Objective - To evaluate the relationship between pain and the HrQOL in patients with PD. METHODS: Eighty-two patients with PD were included and classified into two groups according to the presence of pain. The Hoehn and Yahr scale, the Unified Parkinson's Disease Rating Scale (UPDRS), the Modified Somatic Perception Questionnaire (MSPQ), the Zung Depression Inventory--Self-rating Depression Scale (SDS), the Visual Analogue Scale and the Medical Outcomes Study 36-Item Short Form Health Survey (SF-36) were administered. The factors influencing the pain, HrQOL and parkinsonian manifestations were evaluated. RESULTS: The PD with pain group had higher UPDRS part III scores, lower SF-36 scores, higher SDS scores and higher MSPQ scores than the PD without pain group. The presence of pain, high Hoehn and Yahr stage, advanced age and somatic perception were the factors that had a negative effect on the physical component of the HrQOL. Depression and somatic perception were the most important predictive factors for the mental component of the HrQOL. Depression and poor parkinsonian motor abilities were the leading factors contributing to pain. CONCLUSION: Pain and depression were major detrimental factors affecting the physical and mental aspects of the HrQOL respectively. Therefore, the treatment of pain and depression can be important to improve the HrQOL.

Regional grey matter changes in patients with migraine: a voxel-based morphometry study.

We used voxel-based morphometry (VBM) to compare grey matter volume (GMV) between 20 migraine patients (five with aura and 15 without aura) with normal conventional magnetic resonance imaging findings and 33 healthy controls matched for age and sex. A separate analysis was also performed to delineate a possible correlation between the GMV changes and the headache duration or lifetime headache frequency. When compared with controls, migraine patients had significant GMV reductions in the bilateral insula, motor/premotor, prefrontal, cingulate cortex, right posterior parietal cortex, and orbitofrontal cortex (P < 0.001, uncorrected for multiple comparisons at a voxel level; corrected P < 0.05 after small volume corrections). All regions of the GMV changes were negatively correlated with headache duration and lifetime headache frequency (P < 0.05, Pearson's correlation test). We found evidence for structural grey matter changes in patients with migraine. Our findings of progressive GMV reductions in relation to increasing headache duration and increasing headache frequency suggest that repeated migraine attacks over time result in selective damage to several brain regions involved in central pain processing.

Production of transgenic recloned piglets harboring the human granulocyte-macrophage colony stimulating factor (hGM-CSF) gene from porcine fetal fibroblasts by nuclear transfer.

We used nuclear transfer (NT) to develop transgenic female pigs harboring goat beta-casein promoter/human granulocyte-macrophage colony stimulating factor (hGM-CSF). The expression of hGM-CSF was specific to the mammary gland, and the glycosylation-derived size heterogeneity corresponded to that of the native human protein. Although various cell types have been used to generate cloned animals, little is currently known about the potential use of fibroblasts derived from a cloned fetus as donor cells for nuclear transfer. The developmental potential of porcine cloned fetal fibroblasts transfected with hGM-CSF was evaluated in the present study. Cloned fetal fibroblasts were isolated from a recipient following the transplantation of NT embryos. The cells were transfected with both hGM-CSF and the neomycin resistance gene in order to be used as donor cells for NT. Reconstructed embryos were implanted into six sows during estrus; two of the recipient sows delivered seven healthy female piglets with the hGM-CSF gene (confirmed with PCR and fluorescent in situ hybridization) and microsatellite analysis confirmed that the clones were genetically identical to the donor cells. The expression of hGM-CSF was strong in the mammary glands of a transgenic pig that died a few days prior to parturition (110 d after AI). These results demonstrated that somatic cells derived from a cloned fetus can be used to produce recloned and transgenic pigs.

Potential association of VAMP5 polymorphisms with total colonic aganglionosis in Hirschsprung disease.

BACKGROUND: Hirschsprung disease (HSCR) is a congenital bowel disease caused by the absence of nerve cells in portions of the intestine. Our recent genome-wide association study has identified a variant (rs1254900) of vesicle-associated membrane protein 5 (VAMP5) as a potential risk locus for total colonic aganglionosis (TCA) in HSCR. In addition, VAMP5 is a member of the VAMP/synaptobrevin protein complex, which participates in nerve signal transduction by regulating the vesicular fusion of the neurotransmitter in synaptic transmission. METHODS: A total of 11 single nucleotide polymorphisms (SNPs), including those in the functionally important coding region, were selected on the basis of linkage disequilibrium and genotyped in 187 HSCR patients and 283 unaffected controls by using a TaqMan assay. Logistic analysis was conducted to investigate the possible association between VAMP5 SNPs and the risk of HSCR. KEY RESULTS: Genetic variants of VAMP5 showed increased association signals in the TCA subgroup of HSCR patients (minimum p = 9.69 × 10(-5) , OR = 3.93 at rs10206961) compared to other subgroups, even after Bonferroni correction (pcorr = 0.002). In haplotype analysis, three haplotypes (BL1_ht1, BL2_ht1, and BL2_ht2) were associated with the risk of TCA (minimum pcorr = 0.005). In additional combined analysis after imputation based on our previous GWAS, five SNPs still retained significant associations with the TCA subtype (minimum pcorr = 0.006 at rs10206961). CONCLUSIONS & INFERENCES: Considering that differential genetic effects on the development of the enteric nervous system, our results suggest that VAMP5 may be associated with the TCA of HSCR. However, further replications and functional evaluations are required.

Isothermal anisotropic magnetoresistance in antiferromagnetic metallic IrMn.

Antiferromagnetic spintronics is an emerging field; antiferromagnets can improve the functionalities of ferromagnets with higher response times, and having the information shielded against external magnetic field. Moreover, a large list of aniferromagnetic semiconductors and metals with Néel temperatures above room temperature exists. In the present manuscript, we persevere in the quest for the limits of how large can anisotropic magnetoresistance be in antiferromagnetic materials with very large spin-orbit coupling. We selected IrMn as a prime example of first-class moment (Mn) and spin-orbit (Ir) combination. Isothermal magnetotransport measurements in an antiferromagnetic-metal(IrMn)/ferromagnetic-insulator thin film bilayer have been performed. The metal/insulator structure with magnetic coupling between both layers allows the measurement of the modulation of the transport properties exclusively in the antiferromagnetic layer. Anisotropic magnetoresistance as large as 0.15% has been found, which is much larger than that for a bare IrMn layer. Interestingly, it has been observed that anisotropic magnetoresistance is strongly influenced by the field cooling conditions, signaling the dependence of the found response on the formation of domains at the magnetic ordering temperature.