Epitaxial YBa/sub 2/Cu/sub 3/O/sub y/ thin films grown on silicon with a double buffer of Eu/sub 2/CuO/sub 4//YSZ

We report a double buffer of Eu/sub 2/CuO/sub 4/ (ECO)/YSZ to improve the growth of YBa/sub 2/Cu/sub 3/O/sub y/(YBCO) on Si wafer. The ECO buffer material possesses a very stable 214-T' structure. It has excellent structural and chemical compatibilities with YBCO and YSZ. Our study showed that the epitaxy and crystallinity of YBCO deposited on Si could be considerably enhanced by using such a double buffer of ECO/YSZ. The grown films were characterized by grazing incidence X-ray reflection, rocking curve, SEM, TEM, and surface profiler. It was also found that such a double buffer could lead to a very smooth surface in the YBCO layer.published_or_final_versio

Anti-Neuroinflammatory Effects of Houttuynia cordata Extract on LPS-Stimulated BV-2 Microglia

Purpose: To evaluate the anti-neuroinflammatory effects of Houttuynia cordata extract (H. cordata) in lipopolysaccharide (LPS)-stimulated BV-2 microglial cells, and its anti-oxidant properties.Methods: Anti-oxidant properties were evaluated by 1, 1-diphenyl-2-picryl-hydrazyl (DPPH) radical scavenging assay. Cell viability was assessed by 3-(4, 5-dimethylthiazol-2-yl)-2, 5- diphenyl-tetrazolium bromide (MTT) assay. LPS was used to stimulate BV-2 cells. Nitric oxide (NO) levels were measured using Griess assay. Inducible NO synthase (iNOS) expression, interleukin (IL)-6 expressional level were determined by enzyme-linked immunosorbent assay (ELISA) and Western blot analysis.Results: Ethyl actetae (HC-EA) extract of H. cordata significantly scavenged DPPH free radicals in a concentration-dependent fashion. The increased levels of NO, iNOS and IL-6 in LPS-stimulated BV-2 microglial cells were also suppressed by HC-EA extract in a concentration-dependent manner.Conclusion:The result indicate that the HC-EA extract exhibited strong anti-oxidant properties and inhibited the excessive production of pro-inflammatory mediators, including NO, iNOS and IL-6, in LPSstimulated BV-2 cells. The anti-oxidant phenolic compounds present in HC-EA extract might play an important role in ameliorating neuroinflammatory processes in LPS-stimulated BV-2 microglial cells.Keywords: Houttuynia cordata, DPPH radicals, antioxidant, neuroinflammation, BV-2 cells, iNOS, COX-2, IL-6

Towards a better solution to the shortest common supersequence problem: the deposition and reduction algorithm

BACKGROUND: The problem of finding a Shortest Common Supersequence (SCS) of a set of sequences is an important problem with applications in many areas. It is a key problem in biological sequences analysis. The SCS problem is well-known to be NP-complete. Many heuristic algorithms have been proposed. Some heuristics work well on a few long sequences (as in sequence comparison applications); others work well on many short sequences (as in oligo-array synthesis). Unfortunately, most do not work well on large SCS instances where there are many, long sequences. RESULTS: In this paper, we present a Deposition and Reduction (DR) algorithm for solving large SCS instances of biological sequences. There are two processes in our DR algorithm: deposition process, and reduction process. The deposition process is responsible for generating a small set of common supersequences; and the reduction process shortens these common supersequences by removing some characters while preserving the common supersequence property. Our evaluation on simulated data and real DNA and protein sequences show that our algorithm consistently produces the best results compared to many well-known heuristic algorithms, and especially on large instances. CONCLUSION: Our DR algorithm provides a partial answer to the open problem of designing efficient heuristic algorithm for SCS problem on many long sequences. Our algorithm has a bounded approximation ratio. The algorithm is efficient, both in running time and space complexity and our evaluation shows that it is practical even for SCS problems on many long sequences

Vectorlike Confinement at the LHC

We argue for the plausibility of a broad class of vectorlike confining gauge theories at the TeV scale which interact with the Standard Model predominantly via gauge interactions. These theories have a rich phenomenology at the LHC if confinement occurs at the TeV scale, while ensuring negligible impact on precision electroweak and flavor observables. Spin-1 bound states can be resonantly produced via their mixing with Standard Model gauge bosons. The resonances promptly decay to pseudo-Goldstone bosons, some of which promptly decay to a pair of Standard Model gauge bosons, while others are charged and stable on collider time scales. The diverse set of final states with little background include multiple photons and leptons, missing energy, massive stable charged particles and the possibility of highly displaced vertices in dilepton, leptoquark or diquark decays. Among others, a novel experimental signature of resonance reconstruction out of massive stable charged particles is highlighted. Some of the long-lived states also constitute Dark Matter candidates.Comment: 33 pages, 6 figures. v4: expanded discussion of Z_2 symmetry for stability, one reference adde

Telomerase activity, apoptosis and cell cycle progression in ataxia telangiectasia lymphocytes expressing TCL1

Individuals affected by ataxia telangiectasia (AT) have a marked susceptibility to cancer. Ataxia telangiectasia cells, in addition to defects in cell cycle checkpoints, show dysfunction of apoptosis and of telomeres, which are both thought to have a role in the progression of malignancy. In 1-5% of patients with AT, clonal expansion of T lymphocytes carrying t(14;14) chromosomal translocation, deregulating TCL1 gene(s), has been described. While it is known that these cells can progress with time to a frank leukaemia, the molecular pathway leading to tumorigenesis has not yet been fully investigated. In this study, we compared AT clonal cells, representing 88% of the entire T lymphocytes (AT94-1) and expressing TCL1 oncogene (ATM- TCL1 +), cell cycle progression to T lymphocytes of AT patients without TCL1 expression (ATM- TCL1-) by analysing their spontaneous apoptosis rate, spontaneous telomerase activity and telomere instability. We show that in ATM- TCL1+ lymphocytes, apoptosis rate and cell cycle progression are restored back to a rate comparable with that observed in normal lymphocytes while telomere dysfunction is maintained. © 2003 Cancer Research UK

Plasma levels of phosphorylated tau 181 are associated with cerebral metabolic dysfunction in cognitively impaired and amyloid-positive individuals

Alzheimer’s disease biomarkers are primarily evaluated through MRI, PET and CSF methods in order to diagnose and monitor disease. Recently, advances in the assessment of blood-based biomarkers have shown promise for simple, inexpensive, accessible and minimally invasive tools with diagnostic and prognostic value for Alzheimer’s disease. Most recently, plasma phosphorylated tau181 has shown excellent performance. The relationship between plasma phosphorylated tau181 and cerebral metabolic dysfunction assessed by [18F]fluorodeoxyglucose PET in Alzheimer’s disease is still unknown. This study was performed on 892 older individuals (297 cognitively unimpaired; 595 cognitively impaired) from the Alzheimer’s Disease Neuroimaging Initiative cohort. Plasma phosphorylated tau181 was assessed using single molecular array technology and metabolic dysfunction was indexed by [18F]fluorodeoxyglucose PET. Cross-sectional associations between plasma and CSF phosphorylated tau181 and [18F]fluorodeoxyglucose were assessed using voxelwise linear regression models, with individuals stratified by diagnostic group and by β-amyloid status. Associations between baseline plasma phosphorylated tau181 and longitudinal (24 months) rate of brain metabolic decline were also assessed in 389 individuals with available data using correlations and voxelwise regression models. Plasma phosphorylated tau181 was elevated in β-amyloid positive and cognitively impaired individuals as well as in apolipoprotein E ε4 carriers and was significantly associated with age, worse cognitive performance and CSF phosphorylated tau181. Cross-sectional analyses showed strong associations between plasma phosphorylated tau181 and [18F]fluorodeoxyglucose PET in cognitively impaired and β-amyloid positive individuals. Voxelwise longitudinal analyses showed that baseline plasma phosphorylated tau181 concentrations were significantly associated with annual rates of metabolic decline in cognitively impaired individuals, bilaterally in the medial and lateral temporal lobes. The associations between plasma phosphorylated tau181 and reduced brain metabolism, primarily in cognitively impaired and in β-amyloid positive individuals, supports the use of plasma phosphorylated tau181 as a simple, low-cost, minimally invasive and accessible tool to both assess current and predict future metabolic dysfunction associated with Alzheimer’s disease, comparatively to PET, MRI and CSF methods

Blood phosphorylated tau 181 as a biomarker for Alzheimer's disease: a diagnostic performance and prediction modelling study using data from four prospective cohorts

BACKGROUND: CSF and PET biomarkers of amyloid β and tau accurately detect Alzheimer's disease pathology, but the invasiveness, high cost, and poor availability of these detection methods restrict their widespread use as clinical diagnostic tools. CSF tau phosphorylated at threonine 181 (p-tau181) is a highly specific biomarker for Alzheimer's disease pathology. We aimed to assess whether blood p-tau181 could be used as a biomarker for Alzheimer's disease and for prediction of cognitive decline and hippocampal atrophy. METHODS: We developed and validated an ultrasensitive blood immunoassay for p-tau181. Assay performance was evaluated in four clinic-based prospective cohorts. The discovery cohort comprised patients with Alzheimer's disease and age-matched controls. Two validation cohorts (TRIAD and BioFINDER-2) included cognitively unimpaired older adults (mean age 63-69 years), participants with mild cognitive impairment (MCI), Alzheimer's disease, and frontotemporal dementia. In addition, TRIAD included healthy young adults (mean age 23 years) and BioFINDER-2 included patients with other neurodegenerative disorders. The primary care cohort, which recruited participants in Montreal, Canada, comprised control participants from the community without a diagnosis of a neurological condition and patients referred from primary care physicians of the Canadian National Health Service for specialist care. Concentrations of plasma p-tau181 were compared with established CSF and PET biomarkers and longitudinal measurements using Spearman correlation, area under the curve (AUC), and linear regression analyses. FINDINGS: We studied 37 individuals in the discovery cohort, 226 in the first validation cohort (TRIAD), 763 in the second validation cohort (BioFINDER-2), and 105 in the primary care cohort (n=1131 individuals). In all cohorts, plasma p-tau181 showed gradual increases along the Alzheimer's disease continuum, from the lowest concentrations in amyloid β-negative young adults and cognitively unimpaired older adults, through higher concentrations in the amyloid β-positive cognitively unimpaired older adults and MCI groups, to the highest concentrations in the amyloid β-positive MCI and Alzheimer's disease groups (p<0·001, Alzheimer's disease vs all other groups). Plasma p-tau181 distinguished Alzheimer's disease dementia from amyloid β-negative young adults (AUC=99·40%) and cognitively unimpaired older adults (AUC=90·21-98·24% across cohorts), as well as other neurodegenerative disorders, including frontotemporal dementia (AUC=82·76-100% across cohorts), vascular dementia (AUC=92·13%), progressive supranuclear palsy or corticobasal syndrome (AUC=88·47%), and Parkinson's disease or multiple systems atrophy (AUC=81·90%). Plasma p-tau181 was associated with PET-measured cerebral tau (AUC=83·08-93·11% across cohorts) and amyloid β (AUC=76·14-88·09% across cohorts) pathologies, and 1-year cognitive decline (p=0·0015) and hippocampal atrophy (p=0·015). In the primary care cohort, plasma p-tau181 discriminated Alzheimer's disease from young adults (AUC=100%) and cognitively unimpaired older adults (AUC=84·44%), but not from MCI (AUC=55·00%). INTERPRETATION: Blood p-tau181 can predict tau and amyloid β pathologies, differentiate Alzheimer's disease from other neurodegenerative disorders, and identify Alzheimer's disease across the clinical continuum. Blood p-tau181 could be used as a simple, accessible, and scalable test for screening and diagnosis of Alzheimer's disease. FUNDING: Alzheimer Drug Discovery Foundation, European Research Council, Swedish Research Council, Swedish Alzheimer Foundation, Swedish Dementia Foundation, Alzheimer Society Research Program

Computational Modelling of Patella Femoral Kinematics During Gait Cycle and Experimental Validation

The effect of loading and boundary conditions on patellar mechanics is significant due to the complications arising in patella femoral joints during total knee replacements. To understand the patellar mechanics with respect to loading and motion, a computational model representing the patella femoral joint was developed and validated against experimental results. The computational model was created in IDEAS NX and simulated in MSC ADAMS/VIEW software. The results obtained in the form of internal external rotations and anterior posterior displacements for a new and experimentally simulated specimen for patella femoral joint under standard gait condition were compared with experimental measurements performed on the Leeds ProSim knee simulator. A good overall agreement between the computational prediction and the experimental data was obtained for patella femoral kinematics. Good agreement between the model and the past studies was observed when the ligament load was removed and the medial lateral displacement was constrained. The model is sensitive to ±5 % change in kinematics, frictional, force and stiffness coefficients and insensitive to time step

The hOGG1 Ser326Cys polymorphism and prostate cancer risk: a meta-analysis of 2584 cases and 3234 controls

<p>Abstract</p> <p>Background</p> <p>Genetic polymorphism of human 8-oxoguanine glycosylase 1 (hOGG1) Ser326Cys (rs1052133) has been implicated to alter the risk of prostate cancer, but the results are controversial.</p> <p>Methods</p> <p>Two investigators independently searched the Medline, and Cochrane Library up to June 7, 2011. Summary odds ratios (OR) and 95% confidence interval (CI) for Ser326Cys polymorphism and prostate cancer were calculated. Statistical analysis was performed with the software program Review Manage, version 5.0 and Stata 10.0.</p> <p>Results</p> <p>A total of 8 independent studies, including 2584 cases and 3234 controls, were identified. Our analysis suggested that Ser326Cys was not associated with prostate cancer risk in overall population. In the subgroup analysis, we detected the significant association between Ser326Cys polymorphism and decreased prostate risk in mixed population under additive model (OR = 0.67, 95% CI = 0.50-0.90, P = 0.007), recessive model (OR = 0.68, 95% CI = 0.51-0.91, P = 0.008), and Cys allele versus Ser allele (OR = 0.88, 95% CI = 0.78-0.98, P = 0.02). Subanalysis on Caucasian subjects demonstrated that Ser326Cys was not associated with prostate cancer risk.</p> <p>Conclusion</p> <p>This meta-analysis showed the evidence that hOGG1 Ser326Cys polymorphism was associated with a decreased risk of prostate cancer development in mixed populations.</p