Fits to SO(10) Grand Unified Models

We perform numerical fits of Grand Unified Models based on SO(10), using various combinations of 10-, 120- and 126-dimensional Higgs representations. Both the supersymmetric and non-supersymmetric versions are fitted, as well as both possible neutrino mass orderings. In contrast to most previous works, we perform the fits at the weak scale, i.e. we use RG evolution from the GUT scale, at which the GUT-relations between the various Yukawa coupling matrices hold, down to the weak scale. In addition, the right-handed neutrinos of the seesaw mechanism are integrated out one by one in the RG running. Other new features are the inclusion of recent results on the reactor neutrino mixing angle and the Higgs mass (in the non-SUSY case). As expected from vacuum stability considerations, the low Higgs mass and the large top-quark Yukawa coupling cause some pressure on the fits. A lower top-quark mass, as sometimes argued to be the result of a more consistent extraction from experimental results, can relieve this pressure and improve the fits. We give predictions for neutrino masses, including the effective one for neutrinoless double beta decay, as well as the atmospheric neutrino mixing angle and the leptonic CP phase for neutrino oscillations.Comment: 40 pages, 2 figures. Published versio

On Leptonic Unitary Triangles and Boomerangs

We review the idea of leptonic unitary triangles and extend the concept of the recently proposed unitary boomerangs to the lepton sector. Using a convenient parameterization of the lepton mixing, we provide approximate expressions for the side lengths and the angles of the six different triangles and give examples of leptonic unitary boomerangs. Possible applications of the leptonic unitary boomerangs are also briefly discussed.Comment: 11 pages, 3 figure

Neutrinoless Double Beta Decay, the Inverted Hierarchy and Precision Determination of theta(12)

Ruling out the inverted neutrino hierarchy with neutrinoless double beta decay experiments is possible if a limit on the effective mass below the minimal theoretically possible value is reached. We stress that this lower limit depends strongly on the value of the solar neutrino mixing angle: it introduces an uncertainty of a factor of 2 within its current 3 sigma range. If an experiment is not background-free, a factor of two in effective mass corresponds to a combined factor of 16 improvement for the experimental parameters running time, detector mass, background level and energy resolution. Therefore, a more precise determination of theta(12) is crucial for the interpretation of experimental results and the evaluation of the potential and requirements for future experiments. We give the required half-lifes to exclude (and touch) the inverted hierarchy regime for all double beta decay isotopes with a Q-value above 2 MeV. The nuclear matrix elements from 6 different groups and, if available, their errors are used and compared. We carefully put the calculations on equal footing in what regards various convention issues. We also use our compilation of matrix elements to give the reachable values of the effective mass for a given half-life value.Comment: 26 pages, 6 figures. v2: error corrected (misprint in paper we took a value from), slightly modifying the result

Precision cancer monitoring using a novel, fully integrated, microfluidic array partitioning digital PCR platform.

A novel digital PCR (dPCR) platform combining off-the-shelf reagents, a micro-molded plastic microfluidic consumable with a fully integrated single dPCR instrument was developed to address the needs for routine clinical diagnostics. This new platform offers a simplified workflow that enables: rapid time-to-answer; low potential for cross contamination; minimal sample waste; all within a single integrated instrument. Here we showcase the capability of this fully integrated platform to detect and quantify non-small cell lung carcinoma (NSCLC) rare genetic mutants (EGFR T790M) with precision cell-free DNA (cfDNA) standards. Next, we validated the platform with an established chronic myeloid leukemia (CML) fusion gene (BCR-ABL1) assay down to 0.01% mutant allele frequency to highlight the platform's utility for precision cancer monitoring. Thirdly, using a juvenile myelomonocytic leukemia (JMML) patient-specific assay we demonstrate the ability to precisely track an individual cancer patient's response to therapy and show the patient's achievement of complete molecular remission. These three applications highlight the flexibility and utility of this novel fully integrated dPCR platform that has the potential to transform personalized medicine for cancer recurrence monitoring

Modeling Collective Cell Behavior in Cancer: Perspectives From an Interdisciplinary Conversation

Collective cell behavior contributes to all stages of cancer progression. Understanding how collective behavior emerges through cell-cell interactions and decision-making will advance our understanding of cancer biology and provide new therapeutic approaches. Here, we summarize an interdisciplinary discussion on multicellular behavior in cancer, draw lessons from other scientific disciplines, and identify future directions

microRNAs associated with the different human Argonaute proteins

MicroRNAs (miRNAs) are small noncoding RNAs that function in literally all cellular processes. miRNAs interact with Argonaute (Ago) proteins and guide them to specific target sites located in the 3′-untranslated region (3′-UTR) of target mRNAs leading to translational repression and deadenylation-induced mRNA degradation. Most miRNAs are processed from hairpin-structured precursors by the consecutive action of the RNase III enzymes Drosha and Dicer. However, processing of miR-451 is Dicer independent and cleavage is mediated by the endonuclease Ago2. Here we have characterized miR-451 sequence and structure requirements for processing as well as sorting of miRNAs into different Ago proteins. Pre-miR-451 appears to be optimized for Ago2 cleavage and changes result in reduced processing. In addition, we show that the mature miR-451 only associates with Ago2 suggesting that mature miRNAs are not exchanged between different members of the Ago protein family. Based on cloning and deep sequencing of endogenous miRNAs associated with Ago1–3, we do not find evidence for miRNA sorting in human cells. However, Ago identity appears to influence the length of some miRNAs, while others remain unaffected

Possible alternatives to tri-bimaximal mixing

Possible alternatives to tri-bimaximal mixing are presented based on other symmetry principles, and their predictions for |U(e3)|, sin**2 theta(12) and sin**2 theta(23) are compared to the present neutrino mixing data. In some cases perturbations are required to give better agreement with the data, and the use of a minimal approach is illustrated. Precise experimental determinations of the mixing parameters will be required to decipher the correct mixing pattern and to pin down the appropriate flavor symmetry

A miR-155-dependent microRNA hierarchy in dendritic cell maturation and macrophage activation

MicroRNAs (miRNAs) are small RNAs that play important regulatory roles in many cellular pathways. MiRNAs associate with members of the Argonaute protein family and bind to partially complementary sequences on mRNAs and induce translational repression or mRNA decay. Using deep sequencing and Northern blotting, we characterized miRNA expression in wild type and miR-155-deficient dendritic cells (DCs) and macrophages. Analysis of different stimuli (LPS, LDL, eLDL, oxLDL) reveals a direct influence of miR-155 on the expression levels of other miRNAs. For example, miR-455 is negatively regulated in miR-155-deficient cells possibly due to inhibition of the transcription factor C/EBPbeta by miR-155. Based on our comprehensive data sets, we propose a model of hierarchical miRNA expression dominated by miR-155 in DCs and macrophages

A miR-155-dependent microRNA hierarchy in dendritic cell maturation and macrophage activation

MicroRNAs (miRNAs) are small RNAs that play important regulatory roles in many cellular pathways. MiRNAs associate with members of the Argonaute protein family and bind to partially complementary sequences on mRNAs and induce translational repression or mRNA decay. Using deep sequencing and Northern blotting, we characterized miRNA expression in wild type and miR-155-deficient dendritic cells (DCs) and macrophages. Analysis of different stimuli (LPS, LDL, eLDL, oxLDL) reveals a direct influence of miR-155 on the expression levels of other miRNAs. For example, miR-455 is negatively regulated in miR-155-deficient cells possibly due to inhibition of the transcription factor C/EBPbeta by miR-155. Based on our comprehensive data sets, we propose a model of hierarchical miRNA expression dominated by miR-155 in DCs and macrophages

X-point Position Dependence of Edge Intrinsic Toroidal Rotation on TCV

Recent theoretical work predicts intrinsic toroidal rotation in the tokamak edge to depend strongly on the normalized major radial position of the X-point. With this motivation, we conducted a series of Ohmic L-mode shots on the Tokamak a Configuration Variable, moving the X-point from the inboard to the outboard edge of the last closed flux surface in both lower and upper single null configurations. The edge toroidal rotation evolved from strongly co-current for an inboard X-point to either vanishing or counter-current for an outboard X-point, in agreement with the theoretical expectations. The whole rotation profile shifted roughly rigidly with the edge rotation, resulting in variation of the peak core rotation by more than a factor of two. Core rotation reversals had little effect on the edge rotation. Edge rotation was slightly more counter-current for unfavorable than favorable gradB drift discharges