Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
Filter
Collection
Language
  • 1
    Keywords: CANCER ; EXPRESSION ; COMBINATION ; LUNG ; MODEL ; MODELS ; TOXICITY ; CLASSIFICATION ; liver ; GENE ; GENE-EXPRESSION ; microarray ; validation ; QUALITY ; BREAST ; breast cancer ; BREAST-CANCER ; PERFORMANCE ; gene expression ; MICROARRAY DATA ; HUMANS ; microarrays ; PREDICTION ; PROJECT ; FOLLICULAR LYMPHOMA ; MULTIPLE-MYELOMA ; rodent ; neuroblastoma ; development ; methods ; GENE-EXPRESSION DATA ; DNA MICROARRAYS ; rodents ; RECOMMENDATIONS ; EXPRESSION DATA ; CONTROL MAQC PROJECT ; PUBLISHED MICROARRAY ; RISK-STRATIFICATION
    Abstract: Gene expression data from microarrays are being applied to predict preclinical and clinical endpoints, but the reliability of these predictions has not been established. In the MAQC-II project, 36 independent teams analyzed six microarray data sets to generate predictive models for classifying a sample with respect to one of 13 endpoints indicative of lung or liver toxicity in rodents, or of breast cancer, multiple myeloma or neuroblastoma in humans. In total, 〉30,000 models were built using many combinations of analytical methods. The teams generated predictive models without knowing the biological meaning of some of the endpoints and, to mimic clinical reality, tested the models on data that had not been used for training. We found that model performance depended largely on the endpoint and team proficiency and that different approaches generated models of similar performance. The conclusions and recommendations from MAQC-II should be useful for regulatory agencies, study committees and independent investigators that evaluate methods for global gene expression analysis
    Type of Publication: Journal article published
    Signatur Availability
    BibTip Others were also interested in ...
  • 2
    Publication Date: 2018-04-12
    Description: Introduction Reported adherence to urate-lowering therapy (ULT) in gout varies widely (17%–83.5%). Variability may partly be due to different adherence measurement methods. This review aimed to quantify ULT adherence in adult patients with gout. Methods This analysis examined studies in PubMed, Web of Science, CNKI Scholar and WanFang databases from inception to January 2017. Papers were selected by inclusion and exclusion criteria in the context. Random-effect meta-analysis estimated adherence. Results 22 studies were found by the inclusion criteria, which involved 1 37 699 patients with gout. Four ways to define adherence were reported. Meta-analysis revealed that the overall adherence rate was 47% (95% CI 42% to 52%, I 2 =99.7%). Adherence rate to ULT was 42% (95% CI 37% to 47%, I 2 =99.8%) for prescription claims, 71% (95% CI 63% to 79%) for pill count, 66% (95% CI 50% to 81%, I 2 =86.3%) for self-report and 63% (95% CI 42% to 83%, I 2 =82.9%) for interview, respectively. The influential factor on adherence rate was country of origin. Conclusions Among adult patients with gout, overall adherence rate to ULT was as low as 47%, which suggested that clinicians should pay more attention to medication adherence in patients with gout to effectively improve adherence to ULT.
    Keywords: Open access, Rheumatology
    Electronic ISSN: 2044-6055
    Topics: Medicine
    Published by BMJ Publishing
    Signatur Availability
    BibTip Others were also interested in ...
  • 3
  • 4
    Publication Date: 2018-11-29
    Description: Electrode material design is the key to the development of asymmetric supercapacitors with high electrochemical performances and stability. In this work, Al-doped NiO nanosheet arrays were synthesized using a facile hydrothermal method followed by a calcination process, and the synthesized arrays exhibited a superior pseudocapacitive performance, including a favourable specific capacitance of 2253 ± 105 F g –1 at a current density of 1 A g –1 , larger than that of an undoped NiO electrode (1538 ± 80 F g –1 ). More importantly, the arrays showed a high-rate capability (75% capacitance retention at 20 A g –1 ) and a high cycling stability (approx. 99% maintained after 5000 cycles). The above efficient capacitive performance benefits from the large electrochemically active area and enhanced conductivity of the arrays. Furthermore, an assembled asymmetric supercapacitor based on the Al-doped NiO arrays and N-doped multiwalled carbon nanotube ones delivered a high specific capacitance of 192 ± 23 F g –1 at 0.4 A g –1 with a high-energy density of 215 ± 15 Wh kg –1 and power density of 21.6 kW kg –1 . Additionally, the asymmetric device exhibited a durable cyclic stability (approx. 100% retention after 5000 cycles). This work with the proposed doping method will be beneficial to the construction of high-performance supercapacitor systems.
    Keywords: energy
    Electronic ISSN: 2054-5703
    Topics: Natural Sciences in General
    Published by Royal Society
    Signatur Availability
    BibTip Others were also interested in ...
  • 5
    Publication Date: 2018-02-09
    Description: Eukaryotic chromosomes are folded into higher-order conformations to coordinate genome functions. In addition to long-range chromatin loops, recent chromosome conformation capture (3C)-based studies have indicated higher levels of chromatin structures including compartments and topologically associating domains (TADs), which may serve as units of genome organization and functions. However, the molecular machinery underlying these hierarchically three-dimensional (3D) chromatin architectures remains poorly understood. Via high-throughput assays, including in situ Hi-C, DamID, ChIP-seq, and RNA-seq, we investigated roles of the Heterogeneous Nuclear Ribonucleoprotein U (HNRNPU), a nuclear matrix (NM)-associated protein, in 3D genome organization. Upon the depletion of HNRNPU in mouse hepatocytes, the coverage of lamina-associated domains (LADs) in the genome increases from 53.1% to 68.6%, and a global condensation of chromatin was observed. Furthermore, disruption of HNRNPU leads to compartment switching on 7.5% of the genome, decreases TAD boundary strengths at borders between A (active) and B (inactive) compartments, and reduces chromatin loop intensities. Long-range chromatin interactions between and within compartments or TADs are also significantly remodeled upon HNRNPU depletion. Intriguingly, HNRNPU mainly associates with active chromatin, and 80% of HNRNPU peaks coincide with the binding of CTCF or RAD21. Collectively, we demonstrated that HNRNPU functions as a major factor maintaining 3D chromatin architecture, suggesting important roles of NM-associated proteins in genome organization.
    Electronic ISSN: 1549-5469
    Topics: Biology , Medicine
    Signatur Availability
    BibTip Others were also interested in ...
  • 6
    Publication Date: 2018-02-27
    Description: Feline immunodeficiency virus (FIV) infection in domestic cats is the smallest usable natural model for lentiviral infection studies. FLA-E*01801 was applied to FIV AIDS vaccine research. We determined the crystal structure of FLA-E*01801 complexed with a peptide derived from FIV (gag positions 40 to 48; RMANVSTGR [RMA9]). The A pocket of the FLA-E*01801 complex plays a valuable restrictive role in peptide binding. Mutation experiments and circular-dichroism (CD) spectroscopy revealed that peptides with Asp at the first position (P1) could not bind to FLA-E*01801. The crystal structure and in vitro refolding of the mutant FLA-E*01801 complex demonstrated that Glu 63 and Trp 167 in the A pocket play important roles in restricting P1D. The B pocket of the FLA-E*01801 complex accommodates M/T/A/V/I/L/S residues, whereas the negatively charged F pocket prefers R/K residues. Based on the peptide binding motif, 125 FLA-E*01801-restricted FIV nonapeptides (San Diego isolate) were identified. Our results provide the structural basis for peptide presentation by the FLA-E*01801 molecule, especially A pocket restriction on peptide binding, and identify the potential cytotoxic T lymphocyte (CTL) epitope peptides of FIV presented by FLA-E*01801. These results will benefit both the reasonable design of FLA-E*01801-restricted CTL epitopes and the further development of the AIDS vaccine. IMPORTANCE Feline immunodeficiency virus (FIV) is a viral pathogen in cats, and this infection is the smallest usable natural model for lentivirus infection studies. To examine how FLA I presents FIV epitope peptides, we crystallized and solved the first classic feline major histocompatibility complex class I (MHC-I) molecular structure. Surprisingly, pocket A restricts peptide binding. Trp 167 blocks the left side of pocket A, causing P1D to conflict with Glu 63 . We also identified the FLA-E*01801 binding motif X (except D)-(M/T/A/V/I/L/S)-X-X-X-X-X-X-(R/K) based on structural and biochemical experiments. We identified 125 FLA-E*01801-restricted nonapeptides from FIV. These results are valuable for developing peptide-based FIV and human immunodeficiency virus (HIV) vaccines and for studying how MHC-I molecules present peptides.
    Print ISSN: 0022-538X
    Electronic ISSN: 1098-5514
    Topics: Medicine
    Signatur Availability
    BibTip Others were also interested in ...
  • 7
    Publication Date: 2018-02-10
    Description: As a potential endocrine disruptor, clofibric acid (CA) was investigated in this study for its degradation kinetics and pathways in UV/chlorine process. The results showed that CA in both UV photolysis and UV/chlorine processes could be degraded via pseudo-first-order kinetics, while it almost could not be degraded in the dark chlorination process. The observed rate constant ( k obs ) in UV photolysis was 0.0078 min –1, and increased to 0.0107 min –1 combining with 0.1 mM chlorine. The k obs increased to 0.0447 min –1 with further increasing the chlorine dosage from 0.1 to 1.0 mM, and reached a plateau at higher dosage (greater than 1.0 mM). The higher k obs was obtained at acid solution rather than basic solution. Moreover, the calculated contributions of radical species to k obs indicated that the HO• contributed significantly to CA degradation in acidic conditions, while the reactive chlorine species and UV direct photolysis dominated in neutral and basic solution. The degradation of CA was slightly inhibited in the presence of HCO3– (1 ~ 50 mM), barely affected by the presence of Cl – (1 ~ 200 mM) and greatly suppressed by humic acid (0 ~ 5 mg l –1 ). Thirteen main degradation intermediates and three degradation pathways of CA were identified during UV/chlorine process.
    Keywords: photochemistry, environmental chemistry
    Electronic ISSN: 2054-5703
    Topics: Natural Sciences in General
    Published by Royal Society
    Signatur Availability
    BibTip Others were also interested in ...
  • 8
    Publication Date: 2018-01-12
    Description: We constructed highly oriented and ordered macropores within metal-organic framework (MOF) single crystals, opening up the area of three-dimensional–ordered macro-microporous materials (that is, materials containing both macro- and micropores) in single-crystalline form. Our methodology relies on the strong shaping effects of a polystyrene nanosphere monolith template and a double-solvent–induced heterogeneous nucleation approach. This process synergistically enabled the in situ growth of MOFs within ordered voids, rendering a single crystal with oriented and ordered macro-microporous structure. The improved mass diffusion properties of such hierarchical frameworks, together with their robust single-crystalline nature, endow them with superior catalytic activity and recyclability for bulky-molecule reactions, as compared with conventional, polycrystalline hollow, and disordered macroporous ZIF-8.
    Keywords: Chemistry, Materials Science
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Geosciences , Computer Science , Medicine , Natural Sciences in General , Physics
    Signatur Availability
    BibTip Others were also interested in ...
  • 9
    Publication Date: 2018-06-21
    Description: Poor survival rates of patients with tumors arising from or disseminating into the brain are attributed to an inability to excise all tumor tissue (if operable), a lack of blood-brain barrier (BBB) penetration of chemotherapies/targeted agents, and an intrinsic tumor radio-/chemo-resistance. Ataxia-telangiectasia mutated (ATM) protein orchestrates the cellular DNA damage response (DDR) to cytotoxic DNA double-strand breaks induced by ionizing radiation (IR). ATM genetic ablation or pharmacological inhibition results in tumor cell hypersensitivity to IR. We report the primary pharmacology of the clinical-grade, exquisitely potent (cell IC 50 , 0.78 nM), highly selective [〉10,000-fold over kinases within the same phosphatidylinositol 3-kinase–related kinase (PIKK) family], orally bioavailable ATM inhibitor AZD1390 specifically optimized for BBB penetration confirmed in cynomolgus monkey brain positron emission tomography (PET) imaging of microdosed 11 C-labeled AZD1390 ( K p,uu , 0.33). AZD1390 blocks ATM-dependent DDR pathway activity and combines with radiation to induce G 2 cell cycle phase accumulation, micronuclei, and apoptosis. AZD1390 radiosensitizes glioma and lung cancer cell lines, with p53 mutant glioma cells generally being more radiosensitized than wild type. In in vivo syngeneic and patient-derived glioma as well as orthotopic lung-brain metastatic models, AZD1390 dosed in combination with daily fractions of IR (whole-brain or stereotactic radiotherapy) significantly induced tumor regressions and increased animal survival compared to IR treatment alone. We established a pharmacokinetic-pharmacodynamic-efficacy relationship by correlating free brain concentrations, tumor phospho-ATM/phospho-Rad50 inhibition, apoptotic biomarker (cleaved caspase-3) induction, tumor regression, and survival. On the basis of the data presented here, AZD1390 is now in early clinical development for use as a radiosensitizer in central nervous system malignancies.
    Electronic ISSN: 2375-2548
    Topics: Natural Sciences in General
    Signatur Availability
    BibTip Others were also interested in ...
  • 10
    Publication Date: 2018-03-29
    Description: The 10E8 antibody targets a helical epitope in the membrane-proximal external region (MPER) and transmembrane domain (TMD) of the envelope glycoprotein (Env) subunit gp41 and is among the broadest known neutralizing antibodies against HIV-1. Accordingly, this antibody and its mechanism of action valuably inform the design of effective vaccines and immunotherapies. 10E8 exhibits unusual adaptations to attain specific, high-affinity binding to the MPER at the viral membrane interface. Reversing the charge of the basic paratope surface (from net positive to net negative) reportedly lowered its neutralization potency. Here, we hypothesized that by increasing the net positive charge in similar polar surface patches, the neutralization potency of the antibody may be enhanced. We found that an increased positive charge at this paratope surface strengthened an electrostatic interaction between the antibody and lipid bilayers, enabling 10E8 to interact spontaneously with membranes. Notably, the modified 10E8 antibody did not gain any apparent polyreactivity and neutralized virus with a significantly greater potency. Binding analyses indicated that the optimized 10E8 antibody bound with a higher affinity to the epitope peptide anchored in lipid bilayers and to Env spikes on virions. Overall, our data provide a proof of principle for the rational optimization of 10E8 via manipulation of its interaction with the membrane element of its epitope. However, the observation that a similar mutation strategy did not affect the potency of the first-generation anti-MPER antibody 4E10 shows possible limitations of this principle. Altogether, our results emphasize the crucial role played by the viral membrane in the antigenicity of the MPER-TMD of HIV-1. IMPORTANCE The broadly neutralizing antibody 10E8 blocks infection by nearly all HIV-1 isolates, a capacity which vaccine design seeks to reproduce. Engineered versions of this antibody also represent a promising treatment for HIV infection by passive immunization. Understanding its mechanism of action is therefore important to help in developing effective vaccines and biologics to combat HIV/AIDS. 10E8 engages its helical MPER epitope where the base of the envelope spike submerges into the viral membrane. To enable this interaction, this antibody evolved an unusual property: the ability to interact with the membrane surface. Here, we provide evidence that 10E8 can be made more effective by enhancing its interactions with membranes. Our findings strengthen the idea that to elicit antibodies similar to 10E8, vaccines must reproduce the membrane environment where these antibodies perform their function.
    Print ISSN: 0022-538X
    Electronic ISSN: 1098-5514
    Topics: Medicine
    Signatur Availability
    BibTip Others were also interested in ...
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...