Synthesis of (+)-(R)-Tiruchanduramine

The absolute stereochemistry of the marine alkaloid (+)-(R)-tiruchanduramine was established via a convergent total synthesis in six steps and 15.5% overall yield from Fmoc-D-Dab(Boc)-OH

A novel CXCR4 antagonist counteracts paradoxical generation of cisplatin-induced pro-metastatic niches in lung cancer

Platinum-based chemotherapy remains widely used in advanced non-small cell lung cancer (NSCLC) despite experimental evidence of its potential to induce long-term detrimental effects, including the promotion of pro-metastatic microenvironments. In this study, we investigated the interconnected pathways underlying the promotion of cisplatin-induced metastases. In tumor-free mice, cisplatin treatment resulted in an expansion in the bone marrow of CCR2+CXCR4+Ly6Chigh inflammatory monocytes (IMs) and an increase in lung levels of stromal SDF-1, the CXCR4 ligand. In experimental lung metastasis assays, cisplatin-induced IMs promoted the extravasation of tumor cells and the expansion of CD133+CXCR4+ metastasis-initiating cells (MICs). Peptide R, a novel CXCR4 inhibitor designed as an SDF-1 mimetic peptide, prevented cisplatin-induced IM expansion, the recruitment of IMs into the lungs, and the promotion of metastasis. At the primary tumor site, cisplatin treatment reduced tumor size while simultaneously inducing tumor release of SDF-1, MIC expansion, and recruitment of pro-invasive CXCR4+ macrophages. Co-recruitment of MICs and CCR2+CXCR4+ IMs to distant SDF-1-enriched sites also promoted spontaneous metastases that were prevented by CXCR4 blockade. In clinical specimens from NSCLC patients SDF-1 levels were found to be higher in platinum-treated samples and related to a worse clinical outcome. Our findings reveal that activation of the CXCR4/SDF-1 axis specifically mediates the pro-metastatic effects of cisplatin and suggest CXCR4 blockade as a possible novel combination strategy to control metastatic disease

Detección de PVY y PLRV por RT-qPCR en tubérculos de papa, como estudio de una alternativa de diagnóstico en la certificación de papa semilla

El cultivo de papa es afectado por virus que disminuyen rendimiento o calidad de tubérculospara simiente o uso industrial. Por eso, INASE incluye los virus PVY, PVX, PLRV y PVS en lafiscalización de tubérculos simiente. Como inicio de un proyecto que incluye los cuatro virus, seevaluaron los primers PVY182 (Agindotan et al., 2007), PLRV336 (Bostan y Peker, 2009) yPLRV390 (Peiman y Xie, 2006) para detectar PVY y PLRV. De plantas de 40 días obtenidasdesde papas infectadas con PVY o PLRV (y desde papas sanas) se extrajo ARN con protocoloTrizol®, se realizó retrotranscripción con enzima MMLV de Invitrogen® y amplificación por RTqPCR con intercalante Evagreen de un control interno de ARN vegetal. Se realizaron ademásgradientes de temperatura para optimizar el uso de los primers. En la detección de PVY se logróamplificar el producto de peso molecular esperado (182 pb) y se confirmó su identidad porsecuenciación Sanger y análisis bioinformático (BLAST). No se obtuvieron aún los productos deamplificación esperados con PLRV336 y 390 con el material infectado con PLRV analizadohasta el momento, por lo que se repetirán pruebas con nuevos tubérculos. Se ha planificadoademás utilizar los mismos modelos experimentales para evaluar primers para PVX y PVS.Estos primeros estudios, con resultados promisorios para PVY, validarán una tecnología de altasensibilidad y especificidad adoptable a futuro para certificar tubérculos simiente de papa.Fil: Giustina, S.. Fares Taie Instituto de Análisis; ArgentinaFil: Fares Taie, H.. Fares Taie Instituto de Análisis; ArgentinaFil: Rosso, C.. Clonar S.A.; ArgentinaFil: Perotto, Maria Cecilia. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigaciones Agropecuarias. Instituto de Patología Vegetal; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Clemente, G.. Universidad Nacional de Mar del Plata; ArgentinaFil: Medici, Sandra Karina. Universidad Nacional de Mar del Plata. Instituto de Investigaciones En Produccion, Sanidad y Ambiente. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - Mar del Plata. Instituto de Investigaciones En Produccion, Sanidad y Ambiente.; ArgentinaFil: Quintana, Silvina. Universidad Nacional de Mar del Plata. Instituto de Investigaciones En Produccion, Sanidad y Ambiente. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - Mar del Plata. Instituto de Investigaciones En Produccion, Sanidad y Ambiente.; Argentina5to Congreso Argentino de Fitopatología y 59º Reunión APS División CaribeCorrientesArgentinaAsociación Argentina de Fitopatólogo

Simulation of Quantum Magnetism in Mixed Spin Systems with Impurity Doped Ion Crystal

We propose the realization of linear crystals of cold ions which contain different atomic species for investigating quantum phase transitions and frustration effects in spin system beyond the commonly discussed case of $s=1/2$. Mutual spin-spin interactions between ions can be tailored via the Zeeman effect by applying oscillating magnetic fields with strong gradients. Further, collective vibrational modes in the mixed ion crystal can be used to enhance and to vary the strength of spin-spin interactions and even to switch those forces from a ferro- to an antiferromagnetic character. We consider the behavior of the effective spin-spin couplings in an ion crystal of spin-1/2 ions doped with high magnetic moment ions with spin S=3. We analyze the ground state phase diagram and find regions with different spin orders including ferrimagnetic states. In the most simple non-trivial example we deal with a linear $\{$Ca$^+$, Mn$^+$, Ca$^+\}$ crystal with spins of \{1/2,3,1/2}. To show the feasibility with current state-of-the-art experiments, we discuss how quantum phases might be detected using a collective Stern-Gerlach effect of the ion crystal and high resolution spectroscopy. Here, the state-dependent laser-induced fluorescence of the indicator spin-1/2 ion, of species $^{40}$Ca$^+$, reveals also the spin state of the simulator spin-3 ions, $^{50}$Mn$^+$ as this does not possess suitable levels for optical excitation and detection.Comment: 15 pages, 5 figure

Mapping the Two-Component Atomic Fermi Gas to the Nuclear Shell-Model

The physics of a two-component cold fermi gas is now frequently addressed in laboratories. Usually this is done for large samples of tens to hundreds of thousands of particles. However, it is now possible to produce few-body systems (1-100 particles) in very tight traps where the shell structure of the external potential becomes important. A system of two-species fermionic cold atoms with an attractive zero-range interaction is analogous to a simple model of nucleus in which neutrons and protons interact only through a residual pairing interaction. In this article, we discuss how the problem of a two-component atomic fermi gas in a tight external trap can be mapped to the nuclear shell model so that readily available many-body techniques in nuclear physics, such as the Shell Model Monte Carlo (SMMC) method, can be directly applied to the study of these systems. We demonstrate an application of the SMMC method by estimating the pairing correlations in a small two-component Fermi system with moderate-to-strong short-range two-body interactions in a three-dimensional harmonic external trapping potential.Comment: 13 pages, 3 figures. Final versio

Designing spin-spin interactions with one and two dimensional ion crystals in planar micro traps

We discuss the experimental feasibility of quantum simulation with trapped ion crystals, using magnetic field gradients. We describe a micro structured planar ion trap, which contains a central wire loop generating a strong magnetic gradient of about 20 T/m in an ion crystal held about 160 \mu m above the surface. On the theoretical side, we extend a proposal about spin-spin interactions via magnetic gradient induced coupling (MAGIC) [Johanning, et al, J. Phys. B: At. Mol. Opt. Phys. 42 (2009) 154009]. We describe aspects where planar ion traps promise novel physics: Spin-spin coupling strengths of transversal eigenmodes exhibit significant advantages over the coupling schemes in longitudinal direction that have been previously investigated. With a chip device and a magnetic field coil with small inductance, a resonant enhancement of magnetic spin forces through the application of alternating magnetic field gradients is proposed. Such resonantly enhanced spin-spin coupling may be used, for instance, to create Schr\"odinger cat states. Finally we investigate magnetic gradient interactions in two-dimensional ion crystals, and discuss frustration effects in such two-dimensional arrangements.Comment: 20 pages, 13 figure

An angiopoietin 2, FGF23, and BMP10 biomarker signature differentiates atrial fibrillation from other concomitant cardiovascular conditions

Abstract Early detection of atrial fibrillation (AF) enables initiation of anticoagulation and early rhythm control therapy to reduce stroke, cardiovascular death, and heart failure. In a cross-sectional, observational study, we aimed to identify a combination of circulating biomolecules reflecting different biological processes to detect prevalent AF in patients with cardiovascular conditions presenting to hospital. Twelve biomarkers identified by reviewing literature and patents were quantified on a high-precision, high-throughput platform in 1485 consecutive patients with cardiovascular conditions (median age 69 years [Q1, Q3 60, 78]; 60% male). Patients had either known AF (45%) or AF ruled out by 7-day ECG-monitoring. Logistic regression with backward elimination and a neural network approach considering 7 key clinical characteristics and 12 biomarker concentrations were applied to a randomly sampled discovery cohort (n = 933) and validated in the remaining patients (n = 552). In addition to age, sex, and body mass index (BMI), BMP10, ANGPT2, and FGF23 identified patients with prevalent AF (AUC 0.743 [95% CI 0.712, 0.775]). These circulating biomolecules represent distinct pathways associated with atrial cardiomyopathy and AF. Neural networks identified the same variables as the regression-based approach. The validation using regression yielded an AUC of 0.719 (95% CI 0.677, 0.762), corroborated using deep neural networks (AUC 0.784 [95% CI 0.745, 0.822]). Age, sex, BMI and three circulating biomolecules (BMP10, ANGPT2, FGF23) are associated with prevalent AF in unselected patients presenting to hospital. Findings should be externally validated. Results suggest that age and different disease processes approximated by these three biomolecules contribute to AF in patients. Our findings have the potential to improve screening programs for AF after external validation