Project description:Developing promising treatments in biomedicine often requires aggregation and analysis of data from disparate sources across the healthcare and research spectrum. To facilitate these approaches, there is a growing focus on supporting interoperation of datasets by standardizing data-capture and reporting requirements. Common Data Elements (CDEs)-precise specifications of questions and the set of allowable answers to each question-are increasingly being adopted to help meet these standardization goals. While CDEs can provide a strong conceptual foundation for interoperation, there are no widely recognized serialization or interchange formats to describe and exchange their definitions. As a result, CDEs defined in one system cannot be easily be reused by other systems. An additional problem is that current CDE-based systems tend to be rather heavyweight and cannot be easily adopted and used by third-parties. To address these problems, we developed extensions to a metadata management system called the CEDAR Workbench to provide a platform to simplify the creation, exchange, and use of CDEs. We show how the resulting system allows users to quickly define and share CDEs and to immediately use these CDEs to build and deploy Web-based forms to acquire conforming metadata. We also show how we incorporated a large CDE library from the National Cancer Institute's caDSR system and made these CDEs publicly available for general use.
Project description:Nanofabrication has seen an increasing demand for applications in many fields of science and technology, but its production still requires relatively difficult, time-consuming, and expensive processes. Here we report a simple but very effective one dimensional (1D) nano-patterning technology that suggests a new nanofabrication method. This new technique involves the control of naturally propagating cracks initiated through simple, manually generated indentation, obviating the necessity of complicated equipment and elaborate experimental environments such as those that employ clean rooms, high vacuums, and the fastidious maintenance of processing temperatures. The channel fabricated with this technique can be as narrow as 10?nm with unlimited length and very high cross-sectional aspect ratio, an accomplishment difficult even for a state-of-the-art technology such as e-beam lithography. More interestingly, the fabrication speed can be controlled and achieved to as little as several hundred micrometers per second. Along with the simplicity and real-time fabrication capability of the technique, this tunable fabrication speed makes the method introduced here the authentic nanofabrication for in situ experiments.
Project description:Floret fertility is a key determinant of the number of grains per inflorescence in cereals. During the evolution of wheat (Triticum sp.), floret fertility has increased, such that current bread wheat (Triticum aestivum) cultivars set three to five grains per spikelet. However, little is known regarding the genetic basis of floret fertility. The locus Grain Number Increase 1 (GNI1) is shown here to be an important contributor to floret fertility. GNI1 evolved in the Triticeae through gene duplication. The gene, which encodes a homeodomain leucine zipper class I (HD-Zip I) transcription factor, was expressed most abundantly in the most apical floret primordia and in parts of the rachilla, suggesting that it acts to inhibit rachilla growth and development. The level of GNI1 expression has decreased over the course of wheat evolution under domestication, leading to the production of spikes bearing more fertile florets and setting more grains per spikelet. Genetic analysis has revealed that the reduced-function allele GNI-A1 contributes to the increased number of fertile florets per spikelet. The RNAi-based knockdown of GNI1 led to an increase in the number of both fertile florets and grains in hexaploid wheat. Mutants carrying an impaired GNI-A1 allele out-yielded WT allele carriers under field conditions. The data show that gene duplication generated evolutionary novelty affecting floret fertility while mutations favoring increased grain production have been under selection during wheat evolution under domestication.
Project description:Traditionally, scanning probe lithography tools are limited in resolution by the radius of curvature of the tip used. Herein, an approach is described for patterning the ridge of piled-up polymer that naturally occurs when a scanning probe is pressed against a soft surface. The use of this phenomenon to transfer patterns to hard materials with 20 nm resolution is demonstrated.
Project description:The ability to handle single molecules as effectively as macroscopic building blocks would enable the construction of complex supramolecular structures inaccessible to self-assembly. The fundamental challenges obstructing this goal are the uncontrolled variability and poor observability of atomic-scale conformations. Here, we present a strategy to work around both obstacles and demonstrate autonomous robotic nanofabrication by manipulating single molecules. Our approach uses reinforcement learning (RL), which finds solution strategies even in the face of large uncertainty and sparse feedback. We demonstrate the potential of our RL approach by removing molecules autonomously with a scanning probe microscope from a supramolecular structure. Our RL agent reaches an excellent performance, enabling us to automate a task that previously had to be performed by a human. We anticipate that our work opens the way toward autonomous agents for the robotic construction of functional supramolecular structures with speed, precision, and perseverance beyond our current capabilities.
Project description:There has been a compelling demand of fabricating high-resolution complex three-dimensional (3D) structures in nanotechnology. While two-photon lithography (TPL) largely satisfies the need since its introduction, its low writing speed and high cost make it impractical for many large-scale applications. We report a digital holography-based TPL platform that realizes parallel printing with up to 2000 individually programmable laser foci to fabricate complex 3D structures with 90 nm resolution. This effectively improves the fabrication rate to 2,000,000 voxels/sec. The promising result is enabled by the polymerization kinetics under a low-repetition-rate regenerative laser amplifier, where the smallest features are defined via a single laser pulse at 1 kHz. We have fabricated large-scale metastructures and optical devices of up to centimeter-scale to validate the predicted writing speed, resolution, and cost. The results confirm our method provides an effective solution for scaling up TPL for applications beyond laboratory prototyping.
Project description:Shaping ceramic materials at the nanoscale in 3D is a phenomenal engineering challenge, that can offer new opportunities in a number of industrial applications, including metamaterials, nano-electromechanical systems, photonic crystals, and damage-tolerant lightweight materials. 3D fabrication of sub-micrometer ceramic structures can be performed by two-photon laser writing of a preceramic polymer. However, polymer conversion to a fully ceramic material has proven so far unfeasible, due to lack of suitable precursors, printing complexity, and high shrinkage during ceramic conversion. Here, it is shown that this goal can be achieved through an appropriate engineering of both the material and the printing process, enabling the fabrication of preceramic 3D shapes and their transformation into dense and crack-free SiOC ceramic components with highly complex, 3D sub-micrometer architectures. This method allows for the manufacturing of components with any 3D specific geometry with fine details down to 450 nm, rapidly printing structures up to 100 µm in height that can be converted into ceramic objects possessing sub-micrometer features, offering unprecedented opportunities in different application fields.
Project description:Meiotic crossovers shuffle parental genetic information, providing novel combinations of alleles on which natural or artificial selection can act. However, crossover events are relatively rare, typically one to three exchange points per chromosome pair. Recent work has identified three pathways limiting meiotic crossovers in Arabidopsis thaliana that rely on the activity of FANCM [Crismani W, et al. (2012) Science 336:1588-1590], RECQ4 [Séguéla-Arnaud M, et al. (2015) Proc Natl Acad Sci USA 112:4713-4718], and FIGL1 [Girard C, et al. (2015) PLoS Genet 11:e1005369]. Here we analyzed recombination in plants in which one, two, or all three of these pathways were disrupted in both pure line and hybrid contexts. The greatest effect was observed when combining recq4 and figl1 mutations, which increased the hybrid genetic map length from 389 to 3,037 cM. This corresponds to an unprecedented 7.8-fold increase in crossover frequency. Disrupting the three pathways did not further increase recombination, suggesting that some upper limit had been reached. The increase in crossovers is not uniform along chromosomes and rises from centromere to telomere. Finally, although in wild type recombination is much higher in male meiosis than in female meiosis (490 cM vs. 290 cM), female recombination is higher than male recombination in recq4 figl1 (3,200 cM vs. 2,720 cM), suggesting that the factors that make wild-type female meiosis less recombinogenic than male wild-type meiosis do not apply in the mutant context. The massive increase in recombination observed in recq4 figl1 hybrids opens the possibility of manipulating recombination to enhance plant breeding efficiency.
Project description:Local bandgap tuning in two-dimensional (2D) materials is of significant importance for electronic and optoelectronic devices but achieving controllable and reproducible strain engineering at the nanoscale remains a challenge. Here, we report on thermomechanical nanoindentation with a scanning probe to create strain nanopatterns in 2D transition metal dichalcogenides and graphene, enabling arbitrary patterns with a modulated bandgap at a spatial resolution down to 20 nm. The 2D material is in contact via van der Waals interactions with a thin polymer layer underneath that deforms due to the heat and indentation force from the heated probe. Specifically, we demonstrate that the local bandgap of molybdenum disulfide (MoS2) is spatially modulated up to 10% and is tunable up to 180 meV in magnitude at a linear rate of about -70 meV per percent of strain. The technique provides a versatile tool for investigating the localized strain engineering of 2D materials with nanometer-scale resolution.
Project description:Head and neck squamous cell carcinoma (HNSCC) represents a model of escape from anti-tumor immunity. The high frequency of p53 tumor suppressor loss in HNSCC leads to genomic instability and immune stimulation through the generation of neoantigens. However, the aggressive nature of HNSCC tumors and significant rates of resistance to conventional therapies highlights the ability of HNSCC to evade this immune response. Advances in understanding the role of co-stimulatory and immune checkpoint receptors in HNSCC-mediated immunosuppression lay the foundation for development of novel therapeutic approaches. This article provides an overview of these co-stimulatory and immune checkpoint pathways, as well as a review of preclinical and clinical evidence supporting the modulation of these pathways in HNSCC. Finally, the synergistic potential of combining these approaches is discussed, along with an update of current clinical trials evaluating combinations of immune-based therapies in HNSCC patients.