Anisotropic Electronic Structure of the Kondo Semiconductor CeFe2Al10 Studied by Optical Conductivity

We report temperature-dependent polarized optical conductivity [$\sigma(\omega)$] spectra of CeFe$_2$Al$_{10}$, which is a reference material for CeRu$_2$Al$_{10}$ and CeOs$_2$Al$_{10}$ with an anomalous magnetic transition at 28 K. The $\sigma(\omega)$ spectrum along the b-axis differs greatly from that in the $ac$-plane, indicating that this material has an anisotropic electronic structure. At low temperatures, in all axes, a shoulder structure due to the optical transition across the hybridization gap between the conduction band and the localized $4f$ states, namely $c$-$f$ hybridization, appears at 55 meV. However, the gap opening temperature and the temperature of appearance of the quasiparticle Drude weight are strongly anisotropic indicating the anisotropic Kondo temperature. The strong anisotropic nature in both electronic structure and Kondo temperature is considered to be relevant the anomalous magnetic phase transition in CeRu$_2$Al$_{10}$ and CeOs$_2$Al$_{10}$.Comment: 5 pages, 4 figure

Machine learning assisted real-time deformability cytometry of CD34+ cells allows to identify patients with myelodysplastic syndromes

Diagnosis of myelodysplastic syndrome (MDS) mainly relies on a manual assessment of the peripheral blood and bone marrow cell morphology. The WHO guidelines suggest a visual screening of 200 to 500 cells which inevitably turns the assessor blind to rare cell populations and leads to low reproducibility. Moreover, the human eye is not suited to detect shifts of cellular properties of entire populations. Hence, quantitative image analysis could improve the accuracy and reproducibility of MDS diagnosis. We used real-time deformability cytometry (RT-DC) to measure bone marrow biopsy samples of MDS patients and age-matched healthy individuals. RT-DC is a high-throughput (1000 cells/s) imaging flow cytometer capable of recording morphological and mechanical properties of single cells. Properties of single cells were quantified using automated image analysis, and machine learning was employed to discover morpho-mechanical patterns in thousands of individual cells that allow to distinguish healthy vs. MDS samples. We found that distribution properties of cell sizes differ between healthy and MDS, with MDS showing a narrower distribution of cell sizes. Furthermore, we found a strong correlation between the mechanical properties of cells and the number of disease-determining mutations, inaccessible with current diagnostic approaches. Hence, machine-learning assisted RT-DC could be a promising tool to automate sample analysis to assist experts during diagnosis or provide a scalable solution for MDS diagnosis to regions lacking sufficient medical experts

Constraining Deformation in the North Pamir and the Westernmost Tarim Basin

Abstract HKT-ISTP 2013 A

Comprehensive Analysis of the 16p11.2 Deletion and Null Cntnap2 Mouse Models of Autism Spectrum Disorder

Autism spectrum disorder comprises several neurodevelopmental conditions presenting symptoms in social communication and restricted, repetitive behaviors. A major roadblock for drug development for autism is the lack of robust behavioral signatures predictive of clinical efficacy. To address this issue, we further characterized, in a uniform and rigorous way, mouse models of autism that are of interest because of their construct validity and wide availability to the scientific community. We implemented a broad behavioral battery that included but was not restricted to core autism domains, with the goal of identifying robust, reliable phenotypes amenable for further testing. Here we describe comprehensive findings from two known mouse models of autism, obtained at different developmental stages, using a systematic behavioral test battery combining standard tests as well as novel, quantitative, computer-vision based systems. The first mouse model recapitulates a deletion in human chromosome 16p11.2, found in 1% of individuals with autism. The second mouse model harbors homozygous null mutations in Cntnap2, associated with autism and Pitt-Hopkins-like syndrome. Consistent with previous results, 16p11.2 heterozygous null mice, also known as Del(7Slx1b-Sept1)4Aam weighed less than wild type littermates displayed hyperactivity and no social deficits. Cntnap2 homozygous null mice were also hyperactive, froze less during testing, showed a mild gait phenotype and deficits in the three-chamber social preference test, although less robust than previously published. In the open field test with exposure to urine of an estrous female, however, the Cntnap2 null mice showed reduced vocalizations. In addition, Cntnap2 null mice performed slightly better in a cognitive procedural learning test. Although finding and replicating robust behavioral phenotypes in animal models is a challenging task, such functional readouts remain important in the development of therapeutics and we anticipate both our positive and negative findings will be utilized as a resource for the broader scientific community

The frequency of NPM1 mutations in childhood acute myeloid leukemia

<p>Abstract</p> <p>Background</p> <p>Mutations in the nucleophosmin <it>(NPM1) </it>gene have been solely associated with childhood acute myeloid leukemia (AML). We evaluated the frequency of <it>NPM1 </it>mutations in childhood AML, their relation to clinical and cytogenetic features and the presence of common <it>FLT3 </it>and <it>RAS </it>mutations.</p> <p>Results</p> <p><it>NPM1 </it>mutations were found in 8% of cases. They involved the typical type 'A' mutation and one novel mutation characterized by two individual base pair substitutions, which resulted in 2 amino acid changes (W290) and (S293) in the NPM protein. <it>FLT3</it>/ITD mutations were observed in 12% of the cases and in one <it>NPM1-</it>mutated case bearing also t(8;21) (q22;q22). No common <it>RAS </it>mutations were identified.</p> <p>Conclusions</p> <p>A relatively consistent <it>NPM1 </it>mutation rate was observed, but with variations in types of mutations. The role of different types of <it>NPM1 </it>mutations, either individually or in the presence of other common gene mutations may be essential for childhood AML prognosis.</p

Rapid Diagnostic Algorithms as a Screening Tool for Tuberculosis: An Assessor Blinded Cross-Sectional Study

Background: A major obstacle to effectively treat and control tuberculosis is the absence of an accurate, rapid, and low-cost diagnostic tool. A new approach for the screening of patients for tuberculosis is the use of rapid diagnostic classification algorithms. Methods: We tested a previously published diagnostic algorithm based on four biomarkers as a screening tool for tuberculosis in a Central European patient population using an assessor-blinded cross-sectional study design. In addition, we developed an improved diagnostic classification algorithm based on a study population at a tertiary hospital in Vienna, Austria, by supervised computational statistics. Results: The diagnostic accuracy of the previously published diagnostic algorithm for our patient population consisting of 206 patients was 54% (CI: 47%–61%). An improved model was constructed using inflammation parameters and clinical information. A diagnostic accuracy of 86% (CI: 80%–90%) was demonstrated by 10-fold cross validation. An alternative model relying solely on clinical parameters exhibited a diagnostic accuracy of 85% (CI: 79%–89%). Conclusion: Here we show that a rapid diagnostic algorithm based on clinical parameters is only slightly improved by inclusion of inflammation markers in our cohort. Our results also emphasize the need for validation of new diagnostic algorithms in different settings and patient populations

Mobile phones are a viable option for surveying young Australian women: a comparison of two telephone survey methods

<p>Abstract</p> <p>Background</p> <p>Households with fixed-line telephones have decreased while mobile (cell) phone ownership has increased. We therefore sought to examine the feasibility of recruiting young women for a national health survey through random digit dialling mobile phones.</p> <p>Methods</p> <p>Two samples of women aged 18 to 39 years were surveyed by random digit dialling fixed and mobile numbers. We compared participation rates and responses to a questionnaire between women surveyed by each contact method.</p> <p>Results</p> <p>After dialling 5,390 fixed-lines and 3,697 mobile numbers, 140 and 128 women were recruited respectively. Among women contacted and found to be eligible, participation rates were 74% for fixed-lines and 88% for mobiles. Taking into account calls to numbers where eligibility was unknown (e.g. unanswered calls) the estimated response rates were 54% and 45% respectively. Of women contacted by fixed-line, 97% reported having a mobile while 61% of those contacted by mobile reported having a fixed-line at home. After adjusting for age, there were no significant differences between mobile-only and fixed-line responders with respect to education, residence, and various health behaviours; however compared to those with fixed-lines, mobile-only women were more likely to identify as Indigenous (OR 4.99, 95%CI 1.52-16.34) and less likely to live at home with their parents (OR 0.09, 95%CI 0.03-0.29).</p> <p>Conclusions</p> <p>Random digit dialling mobile phones to conduct a health survey in young Australian women is feasible, gives a comparable response rate and a more representative sample than dialling fixed-lines only. Telephone surveys of young women should include mobile dialling.</p

Targeting BTK for the treatment of FLT3-ITD mutated acute myeloid leukemia

Approximately 20% of patients with acute myeloid leukaemia (AML) have a mutation in FMS-like-tyrosine-kinase-3 (FLT3). FLT3 is a trans-membrane receptor with a tyrosine kinase domain which, when activated, initiates a cascade of phosphorylated proteins including the SRC family of kinases. Recently our group and others have shown that pharmacologic inhibition and genetic knockdown of Bruton's tyrosine kinase (BTK) blocks AML blast proliferation, leukaemic cell adhesion to bone marrow stromal cells as well as migration of AML blasts. The anti-proliferative effects of BTK inhibition in human AML are mediated via inhibition of downstream NF-κB pro-survival signalling however the upstream drivers of BTK activation in human AML have yet to be fully characterised. Here we place the FLT3-ITD upstream of BTK in AML and show that the BTK inhibitor ibrutinib inhibits the survival and proliferation of FLT3-ITD primary AML blasts and AML cell lines. Furthermore ibrutinib inhibits the activation of downstream kinases including MAPK, AKT and STAT5. In addition we show that BTK RNAi inhibits proliferation of FLT3-ITD AML cells. Finally we report that ibrutinib reverses the cyto-protective role of BMSC on FLT3-ITD AML survival. These results argue for the evaluation of ibrutinib in patients with FLT3-ITD mutated AML