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Somatic mutations are major genetic contributors to cancers and many other age-related diseases. Many disease-causing somatic mutations can initiate clonal growth prior to the appearance of any disease symptoms, yet experimental models that can be used to examine clonal abnormalities are limited. We describe a mosaic analysis system with Cre or Tomato (MASCOT) for tracking mutant cells and demonstrate its utility for modeling clonal hematopoiesis. MASCOT can be induced to constitutively express either Cre-GFP or Tomato for lineage tracing of a mutant and a reference group of cells simultaneously. We conducted mosaic analysis to assess functions of the Id3 and/or Tet2 gene in hematopoietic cell development and clonal hematopoiesis. Using Tomato-positive cells as a reference population, we demonstrated the high sensitivity of this system for detecting cell-intrinsic phenotypes during short-term or long-term tracking of hematopoietic cells. Long-term tracking of Tet2 mutant or Tet2/Id3 double-mutant cells in our MASCOT model revealed a dynamic shift from myeloid expansion to lymphoid expansion and subsequent development of lymphoma. This work demonstrates the utility of the MASCOT method in mosaic analysis of single or combined mutations, making the system suitable for modeling somatic mutations identified in humans. [ABSTRACT FROM AUTHOR]

Porous asphalt concrete (PAC) is a particular type of asphalt mixture that has a high content of air voids that is generated because of an open-graded design. The objective of the study is to investigate the effect of the engineering properties of PAC on field performance. Three binders were selected for evaluation: conventional asphalt, polymer-modified asphalt, and highly modified asphalt. Comprehensive laboratory tests, including permeability, resistance to draindown, resistance to disintegration, resistance to rutting, and resistance to indirect traction, were conducted to evaluate the engineering properties of PAC mixtures. Stiff binders were shown to resist against particle loss and to enhance durability of PAC mixes through thick asphalt binder films. According to the laboratory results, a test road was constructed to monitor the performance of PAC pavements with aggregates having a nominal maximum size of 19 mm. Surveys for pavement performance were conducted at scheduled intervals. Test results indicated that the use of polymer-modified binders in surface courses was technically superior to that of traditional asphalt. There were indications of drainage improvement by replacement of conventional asphalt with polymer-modified binders according to measurements in the field. Porous asphalt-wearing layers were shown to maintain drainability for more than 8 years in this study. The engineering properties of PAC mixes obtained from the laboratory corresponded well with pavement performance evaluated in the field. [ABSTRACT FROM AUTHOR]

We investigate the relationship between seismic moment M0 and source duration tw of microearthquakes by using high-quality seismic data recorded with a vertical borehole array installed in central Taiwan. We apply a waveform cross-correlation method to the threecomponent records and identify several event clusters with high waveform similarity, with event magnitudes ranging from 0.3 to 2.0. Three clusters--Clusters A, B and C--contain 11, 8 and 6 events with similar waveforms, respectively. To determine how M0 scales with tw, we remove path effects by using a path-averaged Q. The results indicate a nearly constant tw for events within each cluster, regardless of M0, with mean values of tw being 0.058, 0.056 and 0.034 s for Clusters A, B and C, respectively. Constant tw, independent of M0, violates the commonly used scaling relation tw α M01/3. This constant duration may arise either because all events in a cluster are hosted on the same isolated seismogenic patch, or because the events are driven by external factors of constant duration, such as fluid injections into the fault zone. It may also be related to the earthquake nucleation size. [ABSTRACT FROM AUTHOR]

Leafy flowers are the major symptoms of peanut witches' broom (PnWB) phytoplasma infection in Catharanthus roseus. The orthologs of the phyllody symptoms1 (PHYL1) effector of PnWB from other species of phytoplasma can trigger the proteasomal degradation of several MADS box transcription factors, resulting in leafy flower formation. In contrast, the flowering negative regulator gene SHORT VEGETATIVE PHASE (SVP) was up-regulated in PnWB-infected C. roseus plants, but most microRNA (miRNA) genes had repressed expression. Coincidentally, transgenic Arabidopsis (Arabidopsis thaliana) plants expressing the PHYL1 gene of PnWB (PHYL1 plants), which show leafy flower phenotypes, up-regulate SVP of Arabidopsis (AtSVP) but repress a putative regulatory miRNA of AtSVP, miR396. However, the mechanism by which PHYL1 regulates AtSVP and miR396 is unknown, and the evidence of miR396-mediated AtSVP degradation is lacking. Here, we show that miR396 triggers AtSVP messenger RNA (mRNA) decay using genetic approaches, a reporter assay, and high-throughput degradome profiles. Genetic evidence indicates that PHYL1 plants and atmir396a-1 mutants have higher AtSVP accumulation, whereas the transgenic plants overexpressing MIR396 display lower AtSVP expression. The reporter assay indicated that target-site mutation results in decreasing the miR396-mediated repression efficiency. Moreover, degradome profiles revealed that miR396 triggers AtSVP mRNA decay rather than miRNA-mediated cleavage, implying that AtSVP caused miR396-mediated translation inhibition. We hypothesize that PHYL1 directly or indirectly interferes with miR396-mediated AtSVP mRNA decay and synergizes with other effects (e.g. MADS box transcription factor degradation), resulting in abnormal flower formation. We anticipate our findings to be a starting point for studying the posttranscriptional regulation of PHYL1 effectors in symptom development. [ABSTRACT FROM AUTHOR]

Linear spectral mixture analysis (LSMA) has received wide interests for spectral unmixing in the remote sensing community. This paper introduces a framework called multiplekernel learning-based spectral mixture analysis (MKL-SMA) that integrates a newly proposed MKL method into the training process of LSMA. MKL-SMA allows us to adopt a set of nonlinear basis kernels to better characterize the data so that it can enrich the discriminant capability in classification. Because a single kernel is often insufficient to well present all the data characteristics, MKL-SMA has the advantage of providing a broader range of representation flexibilities; it also eases the kernel selection process because the kernel combination parameters can be learned automatically. Unlike most MKL approaches where complex nonlinear optimization problems are involved in their training process, we derived a closed-form solution of the kernel combination parameters in MKL-SMA. Our method is thus efficient for training and easy to implement. The usefulness of MKL-SMA is demonstrated by conducting real hyperspectral image experiments for performance evaluation. Promising results manifest the effectiveness of the proposed MKL-SMA. [ABSTRACT FROM PUBLISHER]

RNA interference (RNAi) is a potent method of gene silencing that has developed rapidly over the past few years as a result of its extensive importance in the study of genetics, molecular biology and physiology. RNAi technology has also recently yielded significant insight into the innate and adaptive immune systems by helping to elucidate numerous mechanisms that regulate the development, activation and function of cells that mediate immunity. In addition, because of its ability to suppress gene expression effectively, this technique may be used to regulate the immune response for clinical purposes. Nonetheless, before RNAi can be successfully administered into human patients as a medical treatment, it is necessary to overcome several major limitations of this technology, such as inefficient in vivo delivery, incomplete silencing of target genes, non-specific immune responses, and off-target effects. As novel developments and discoveries in molecular biology swiftly continue to unfold, it is likely that RNAi may soon translate into a potent form of in vivo gene silencing with profound applications to vaccination and immunotherapy. In the present review, we examine the current progress of immunological studies employing RNAi and discuss the prospects for the implementation of this technique in the clinical arena. [ABSTRACT FROM AUTHOR]