17O NMR study of the intrinsic magnetic susceptibility and spin dynamics of the quantum kagome antiferromagnet ZnCu3(OH)6Cl2

We report through 17O NMR, an unambiguous local determination of the intrinsic kagome lattice spin susceptibility as well as that created around non-magnetic defects issued from natural Zn/ Cu exchange in the S=1/2 (Cu2+) herbertsmithite ZnCu3(OH)6Cl2 compound. The issue of a singlet-triplet gap is addressed. The magnetic response around a defect is found to markedly differ from that observed in non-frustrated antiferromagnetic materials. Finally, we discuss our relaxation measurements in the light of Cu and Cl NMR data [cond-mat 070314] and suggest a flat q-dependence of the excitations.Comment: Accepted for publication in Phys. Rev. Lett., 3 jan. 2008 Figure 1 has been modified to include a two-components fit of the 17O NMR spectru

Dilemmas in counselling females with the fragile X syndrome

The dilemmas in counselling a mildly retarded female with the fragile X syndrome and her retarded partner are presented. The fragile X syndrome is an X linked mental retardation disorder that affects males and, often less severely, females. Affected females have an increased risk of having affected offspring. The counselling of this couple was complicated by their impaired comprehension which subsequently impaired their thinking on the different options. The woman became pregnant and underwent CVS, which showed an affected male fetus. The pregnancy was terminated. Whether nondirective counselling for this couple was the appropriate method is discussed and the importance of a system oriented approach, through involving relatives, is stressed

The use of the DR CALUX bioassay and indicator polychlorinated biphenyls for screening of elevated levels of dioxins and dioxin-like polychlorinated biphenyls in eel.

The DR CALUX bioassay is a very suitable screening method for dioxins and dioxin-like-PCBs in feed and food. This was, e. g. demonstrated in a survey in the Netherlands to control the dioxin levels in eel. The DR CALUX assay, but also indicator polychlorinated biphenyls (PCB) were evaluated as a screening method. Based on the limit for polychlorinated dibenzo-p-dioxins/dibenzofurans (PCDD/F) [at that time 8 pg toxic equivalents (TEQ)/g eel], and the relation between PCDD/F and dioxin-like-PCB, a decision limit of 30 pg TEQ/g eel was used for screening of 153 field samples. Suspected samples (21) and part of the higher contaminated negative samples (35) were analyzed by GC/MS for dioxins, non-ortho, mono-ortho and indicator PCB, revealing 13 samples exceeding the action limit of 30 pg TEQ/g eel. Only one sample slightly exceeded the dioxin level of 8 pg TEQ/g eel. The relatively low sensitivity for mono-ortho PCB was overcome by the use of reference samples, as shown by the correlation of 0.93 between GC/MS and CALUX determined total TEQ levels. The present data show that the DR CALUX assay can be used for screening of total TEQ levels in eel. The use for dioxins only requires a safe, and therefore relatively low, decision limit. The indicator PCB also showed a good correlation with total TEQ levels, mainly due to the large contribution of the mono-ortho PCB at higher concentrations. The relation with dioxins was very poor and as such indicator PCB seem less suitable than the DR CALUX assay for screening for dioxins only. The present study clearly shows that part of the wild eel samples contains high total TEQ levels and will exceed the future European Union limit of 12 pg TEQ/g eel for dioxins and dioxin-like PCB. Especially at high TEQ levels, dioxin-like PCB contribute most to the total TEQ. In practice, wild eel presents only a minor part of the eel consumed

Dzyaloshinsky-Moriya Anisotropy in the Spin-1/2 Kagom\'e Compound ZnCu3_{3}(OH)6_{6}Cl2_{2}

We report the determination of the Dzyaloshinsky-Moriya interaction, the dominant magnetic anisotropy term in the \kagome spin-1/2 compound {\herbert}. Based on the analysis of the high-temperature electron spin resonance (ESR) spectra, we find its main component $|D_z|=15(1)$ K to be perpendicular to the \kagome planes. Through the temperature dependent ESR line-width we observe a building up of nearest-neighbor spin-spin correlations below $\sim$150 K.Comment: 4 pages, 3 figures, minor modification

Forging Links between Human Mental Retardation–Associated CNVs and Mouse Gene Knockout Models

Rare copy number variants (CNVs) are frequently associated with common neurological disorders such as mental retardation (MR; learning disability), autism, and schizophrenia. CNV screening in clinical practice is limited because pathological CNVs cannot be distinguished routinely from benign CNVs, and because genes underlying patients' phenotypes remain largely unknown. Here, we present a novel, statistically robust approach that forges links between 148 MR–associated CNVs and phenotypes from ∼5,000 mouse gene knockout experiments. These CNVs were found to be significantly enriched in two classes of genes, those whose mouse orthologues, when disrupted, result in either abnormal axon or dopaminergic neuron morphologies. Additional enrichments highlighted correspondences between relevant mouse phenotypes and secondary presentations such as brain abnormality, cleft palate, and seizures. The strength of these phenotype enrichments (>100% increases) greatly exceeded molecular annotations (<30% increases) and allowed the identification of 78 genes that may contribute to MR and associated phenotypes. This study is the first to demonstrate how the power of mouse knockout data can be systematically exploited to better understand genetically heterogeneous neurological disorders

Field-Induced Freezing of a Quantum Spin Liquid on the Kagome Lattice

We report 17O NMR measurements in the S=1/2 Cu2+ kagome antiferromagnet Herbertsmithite ZnCu3(OH)6Cl2 down to 45mK in magnetic fields ranging from 2T to 12T. While Herbertsmithite displays a gapless spin-liquid behavior in zero field, we uncover an instability toward a spin-solid phase at sub-kelvin temperature induced by an applied magnetic field. The latter phase shows largely suppressed moments \lesssim 0.1\muB and gapped excitations. The H-T phase diagram suggests the existence of a quantum critical point at the small but finite magnetic field mu0 Hc=1.55(25)T. We discuss this finding in light of the perturbative Dzyaloshinskii-Moriya interaction which was theoretically proposed to sustain a quantum critical regime for the quantum kagome Heisenberg antiferromagnet model.Comment: One link added for supplemental materials. Published in : Phys. Rev. Lett. 107, 237201 (2011

Analyzing the Estrogen Receptor Status of Liver Metastases with [F-18]-FES-PET in Patients with Breast Cancer

Background: Positron emission tomography (PET) with 16α-[18F]-fluoro-17β-estradiol ([18F]-FES) can visualize estrogen receptor (ER) expression, but it is challenging to determine the ER status of liver metastases, due to high physiological [18F]-FES uptake. We evaluated whether [18F]-FES-PET can be used to determine the ER status of liver metastases, using corresponding liver biopsies as the gold standard. Methods: Patients with metastatic breast cancer (n = 23) were included if they had undergone a [18F]-FES-PET, liver metastasis biopsy, CT-scan, and [18F]-FDG-PET. [18F]-FES-PET scans were assessed by visual and quantitative analysis, tracer uptake was correlated with ER expression measured by immunohistochemical staining and the effects of region-of-interest size and background correction were determined. Results: Visual analysis allowed ER assessment of liver metastases with 100% specificity and 18% sensitivity. Quantitative analysis improved the sensitivity. Reduction of the region-of-interest size did not further improve the results, but background correction improved ER assessment, resulting in 83% specificity and 77% sensitivity. Using separate thresholds for ER+ and ER− metastases, positive and negative predictive values of 100% and 75%, respectively, could be obtained, although 30% of metastases remained inconclusive. Conclusion: In the majority of liver metastases, ER status can be determined with [18F]-FES-PET if background correction and separate thresholds are applied

Mesothelin/CD3 half-life extended bispecific T-cell engager molecule shows specific tumor uptake and distributes to mesothelin and CD3 expressing tissues

BiTE ® (bispecific T-cell engager) molecules exert antitumor activity by binding one arm to CD3 on cytotoxic T-cells and the other arm to a tumor-associated antigen. We generated a fully mouse cross-reactive mesothelin (MSLN)-targeted BiTE molecule that is genetically fused to a Fc-domain for half-life extension, and evaluated biodistribution and tumor targeting of a zirconium-89 (89Zr)-labeled MSLN HLE BiTE molecule in 4T1 breast cancer bearing syngeneic mice with positron emission tomography (PET). Biodistribution of 50 µg 89Zr-MLSN HLE BiTE was studied over time by PET imaging in BALB/c mice and revealed uptake in tumor and lymphoid tissues with an elimination half-life of 63.4 hours. Compared to a non-targeting 89Zr-control HLE BiTE, the 89Zr-MLSN HLE BiTE showed a 2-fold higher tumor uptake and higher uptake in lymphoid tissues. Uptake in the tumor colocalized with mesothelin expression, while uptake in the spleen colocalized with CD3 expression. Evaluation of the effect of protein doses on the biodistribution and tumor targeting of 89Zr-MSLN HLE BiTE revealed for all dose groups that uptake in the spleen was faster than in the tumor (day 1 vs day 5). The lowest dose of 10 µg 89Zr-MSLN HLE BiTE had higher spleen uptake and faster blood clearance compared to higher doses of 50 µg and 200 µg. 89Zr-MSLN HLE BiTE tumor uptake was similar at all doses. Conclusion: The MSLN HLE BiTE showed specific tumor uptake and both arms contributed to the biodistribution profile. These findings support the potential for clinical translation of HLE BiTE molecules