Scalable Spin Amplification with a Gain over a Hundred

We propose a scalable and practical implementation of spin amplification which does not require individual addressing nor a specially tailored spin network. We have demonstrated a gain of 140 in a solid-state nuclear spin system of which the spin polarization has been increased to 0.12 using dynamic nuclear polarization with photoexcited triplet electron spins. Spin amplification scalable to a higher gain opens the door to the single spin measurement for a readout of quantum computers as well as practical applications of nuclear magnetic resonance (NMR) spectroscopy to infinitesimal samples which have been concealed by thermal noise.Comment: 6 pages, 7 figure

Universal patterns in sound amplitudes of songs and music genres

We report a statistical analysis over more than eight thousand songs. Specifically, we investigate the probability distribution of the normalized sound amplitudes. Our findings seems to suggest a universal form of distribution which presents a good agreement with a one-parameter stretched Gaussian. We also argue that this parameter can give information on music complexity, and consequently it goes towards classifying songs as well as music genres. Additionally, we present statistical evidences that correlation aspects of the songs are directly related with the non-Gaussian nature of their sound amplitude distributions.Comment: Accepted for publication as a Brief Report in Physical Review

Severe discrepancies between experiment and theory in the superconducting proximity effect

The superconducting proximity effect is investigated for SN double layers in a regime where the resulting transition temperature T_{c} does not depend on the mean free paths of the films and, within limits, not on the transparency of the interface. This regime includes the thin film limit and the normalized initial slope S_{sn}= (d_{s}/T_{s})|dT_{c}/dd_{n}|. The experimental results for T_{c} are compared with a numerical simulation which was recently developed in our group. The results for the SN double layers can be devided into three groups: (i) When N = Cu, Ag, Au, Mg a disagreement between experiment and theory by a factor of the order of three is observed, (ii) When N = Cd, Zn, Al the disagreement between experiment and theory is reduced to a factor of about 1.5, (iii) When N = In, Sn a reasonably good agreement between experiment and theory is observed

Bone metastases in patients with metastatic breast cancer: morphologic and metabolic monitoring of response to systemic therapy with integrated PET/CT

Purpose: to retrospectively compare morphologic and metabolic changes in bone metastases in response to systemic therapy in patients with metastatic breast cancer (MBC) with integrated positron emission tomography (PET)/computed tomography (CT). Materials and methods: the institutional review board waived the requirement for informed consent and approved this HIPAA-compliant study. A retrospective analysis was performed with 102 women (mean age, 55 years) with MBC who received systemic treatment. All patients underwent integrated PET/CT before and after treatment. Two reviewers analyzed the images in consensus. Morphologic changes, including morphologic patterns, and lesion attenuation were evaluated. Standardized uptake value (SUV) and total lesion glycolysis (TLG) were analyzed to evaluate metabolic changes. Uni- and multivariate analyses were performed to identify factors that enabled response duration (RD) to be predicted. Results: at baseline, the morphologic patterns of the target lesions were lytic (n = 33), sclerotic (n = 22), mixed (n = 42), and unclassified (n = 5). Progression of sclerotic change after treatment was identified in 49 patients (48%). After treatment, the mean attenuation of the lesion increased, whereas the mean SUV and TLG decreased. Increases in attenuation correlated significantly with decreases in SUV (r = -0.510, P < .001) and TLG (r = -0.491, P < . 001). Univariate analysis revealed that the increase in attenuation and the decrease in SUV were potential predictors of RD. Multivariate analysis revealed that an increase in the change in SUV was a significant predictor of RD (relative risk, 2.4; P = .003). Conclusion: a decrease in SUV after treatment was an independent predictor of RD in patients with MBC who had bone metastases

Chronic thyroiditis in patients with advanced breast carcinoma: metabolic and morphologic changes on PET-CT

Purpose: to investigate clinical implications of FDG uptake in the thyroid glands in patients with advanced breast carcinoma by comparing metabolic and morphologic patterns on positron emission tomography (PET)/computed tomography (CT). Methods: the institutional review board waived the requirement for informed consent. A retrospective analysis was performed in 146 women (mean age 54 years) with advanced breast carcinoma who received systemic treatment. All patients underwent PET-CT before and after treatment. All PET-CT studies were reviewed in consensus by two reviewers. Morphologic changes including volume and mean parenchymal density of the thyroid glands were evaluated. Maximum standardized uptake value (SUVmax) and total lesion glycolysis (TLG) were determined to evaluate metabolic changes. These parameters were compared between patients with chronic thyroiditis who received thyroid hormone replacement therapy and those who did not. Results: of the 146 patients, 29 (20%) showed bilaterally diffuse uptake in the thyroid glands on the baseline PET-CT scan. The SUVmax showed a linear relationship with volume (r = 0.428, p = 0.021) and the mean parenchymal density (r = -0.385, p = 0.039) of the thyroid glands. In 21 of the 29 patients (72%) with hypothyroidism who received thyroid hormone replacement therapy, the volume, mean parenchymal density, SUVmax, and TLG of the thyroid glands showed no significant changes. In contrast, 8 of the 29 patients (28%) who did not receive thyroid hormone replacement therapy showed marked decreases in SUVmax and TLG. Conclusion: diffuse thyroid uptake on PET-CT represents active inflammation caused by chronic thyroiditis in patients with advanced breast carcinoma. Diffuse thyroid uptake may also address the concern about subclinical hypothyroidism which develops into overt disease during follow-up

Visualization and measurement of the cell-free layer (CFL) in a microchannel network

In the past years, in vitro blood studies have revealed several significant hemodynamic phenomena that have played a key role in recent developments of biomedical microdevices for cells separation, sorting and analysis. However, the blood flow phenomena happening in complex geometries, such as microchannel networks, have not been fully understood. Thus, it is important to investigate in detail the blood flow behavior occurring at microchannel networks. In the present study, by using a high-speed video microscopy system, we have used two working fluids with different haematocrit (1% Hct and 15% Hct) and we have investigated the cell-free layer (CFL) in a microchannel network composed by asymmetric bifurcations. By using the Z Project method from the image analysis software ImageJ, it was possible to conclude that the successive bifurcations and confluences influence the formation of the CFL not only along the upper and lower wall of the microchannel but also at the region immediately downstream of the confluence apex.The authors acknowledge the financial support provided by the project POCI-01-0145 FEDER-016861 (with associated reference PTDC/QEQ-FTT/4287/2014), UID/EMS/00532/2013 and UID/CEC/00319/2013 funded by FCT (Foundation for Science and Technology), through national funds (PIDDAC), and FEDER through COMPETE2020 - Programa Operacional Competitividade e Internacionalização (POCI). D. Bento acknowledges the PhD scholarship SFRH/BD/91192/2012 granted by FCT. The authors also acknowledge the financial support provided by the project Nos. UID/EMS/00532/2013 and UID/EMS/04077/2013 and the project Nos. UID/EMS/00532/2013, UID/EMS/04077/2013, POCI-01-0145-FEDER-007043, UID/CEC/00319/2013info:eu-repo/semantics/publishedVersio

Effect of DNA Repair Protein Rad18 on Viral Infection

Host factors belonging to the DNA repair machineries are assumed to aid retroviruses in the obligatory step of integration. Here we describe the effect of DNA repair molecule Rad18, a component of the post-replication repair pathway, on viral infection. Contrary to our expectations, cells lacking Rad18 were consistently more permissive to viral transduction as compared to Rad18(+/+) controls. Remarkably, such susceptibility was integration independent, since retroviruses devoid of integration activity also showed enhancement of the initial steps of infection. Moreover, the elevated sensitivity of the Rad18(−/−) cells was also observed with adenovirus. These data indicate that Rad18 suppresses viral infection in a non-specific fashion, probably by targeting incoming DNA. Furthermore, considering data published recently, it appears that the interactions between DNA repair components with incoming viruses, often result in inhibition of the infection rather than cooperation toward its establishment

Targetable Signaling Pathway Mutations Are Associated with Malignant Phenotype in IDH-Mutant Gliomas

Purpose: Isocitrate dehydrogenase (IDH) gene mutations occur in low-grade and high-grade gliomas. We sought to identify the genetic basis of malignant phenotype heterogeneity in IDH-mutant gliomas. Methods: We prospectively implanted tumor specimens from 20 consecutive IDH1-mutant glioma resections into mouse brains and genotyped all resection specimens using a CLIA-certified molecular panel. Gliomas with cancer driver mutations were tested for sensitivity to targeted inhibitors in vitro. Associations between genomic alterations and outcomes were analyzed in patients. Results: By 10 months, 8 of 20 IDH1-mutant gliomas developed intracerebral xenografts. All xenografts maintained mutant IDH1 and high levels of 2-hydroxyglutarate on serial transplantation. All xenograft-producing gliomas harbored “lineage-defining” mutations in CIC (oligodendroglioma) or TP53 (astrocytoma), and 6 of 8 additionally had activating mutations in PIK3CA or amplification of PDGFRA, MET, or N-MYC. Only IDH1 and CIC/TP53 mutations were detected in non–xenograft-forming gliomas (P = 0.0007). Targeted inhibition of the additional alterations decreased proliferation in vitro. Moreover, we detected alterations in known cancer driver genes in 13.4% of IDH-mutant glioma patients, including PIK3CA, KRAS, AKT, or PTEN mutation or PDGFRA, MET, or N-MYC amplification. IDH/CIC mutant tumors were associated with PIK3CA/KRAS mutations whereas IDH/TP53 tumors correlated with PDGFRA/MET amplification. Presence of driver alterations at progression was associated with shorter subsequent progression-free survival (median 9.0 vs. 36.1 months; P = 0.0011). Conclusion: A subset of IDH-mutant gliomas with mutations in driver oncogenes has a more malignant phenotype in patients. Identification of these alterations may provide an opportunity for use of targeted therapies in these patients.Koch Institute Dana Farber/Harvard Cancer Center Bridge Projec

SUMO-1 possesses DNA binding activity

<p>Abstract</p> <p>Background</p> <p>Conjugation of small ubiquitin-related modifiers (SUMOs) is a frequent post-translational modification of proteins. SUMOs can also temporally associate with protein-targets via SUMO binding motifs (SBMs). Protein sumoylation has been identified as an important regulatory mechanism especially in the regulation of transcription and the maintenance of genome stability. The precise molecular mechanisms by which SUMO conjugation and association act are, however, not understood.</p> <p>Findings</p> <p>Using NMR spectroscopy and protein-DNA cross-linking experiments, we demonstrate here that SUMO-1 can specifically interact with dsDNA in a sequence-independent fashion. We also show that SUMO-1 binding to DNA can compete with other protein-DNA interactions at the example of the regulatory domain of Thymine-DNA Glycosylase and, based on these competition studies, estimate the DNA binding constant of SUMO1 in the range 1 mM.</p> <p>Conclusion</p> <p>This finding provides an important insight into how SUMO-1 might exert its activity. SUMO-1 might play a general role in destabilizing DNA bound protein complexes thereby operating in a bottle-opener way of fashion, explaining its pivotal role in regulating the activity of many central transcription and DNA repair complexes.</p