Automatic Synthesis Research Articles

Tone- and Feature-Aware Circular Scribble Art

Circular scribble art is a kind of line drawing where the seemingly random, noisy and shapeless circular scribbles at microscopic scale constitute astonishing grayscale images at macroscopic scale. Such a delicate skill has rendered the creation of circular scribble art a tedious and time-consuming task even for gifted artists. In this work, we present a novel method for automatic synthesis of circular scribble art. The synthesis problem is modeled as tracing along a virtual path using a parametric circular curve. To reproduce the tone and important edge structure of input grayscale images, the system adaptively adjusts the density and structure of virtual path, and dynamically controls the size, drawing speed and orientation of parametric circular curve during the synthesis. We demonstrate the potential of our system using several circular scribble images synthesized from a wide variety of grayscale images. A preliminary experimental studying is conducted to qualitatively and quantitatively evaluate our method. Results report that our method is efficient and generates convincing results comparable to artistic artworks.

PNA Molecular Beacons Assembled by Post-Synthetic Click Chemistry Functionalization.

To avoid the tedious synthesis of functionalized peptide nucleic acid (PNA) monomers for probe development, we proposed a simple approach to modify PNA oligomers by post-synthetic on-resin click chemistry. PNA molecular beacons (MBs) were prepared by incorporation of azide-containing monomers into the oligomer by automatic solid-phase peptide synthesis and subsequent derivatization with pyrene moieties by copper-catalyzed azide-alkyne cycloaddition. Two pyrene-based quencher-free PNA molecular beacons, a stemless MB and one possessing a stem-loop structure, targeting a portion of the cystic fibrosis gene, were successfully synthesized by using this method. Fluorescence studies showed that the stem-loop MB exhibited better discrimination of changes in excimer/monomer ratios as compared to the stemless MB construct.

Automated synthesis and quality analysis of 18F-FMISO based on CFN-MPS-100 module

Objective To synthesize 18F-FMISO and analyze the quality of the product. Methods 1-(2'-nitro-1'-imidazolyl)-2-O-tetrahydropyranyl-O-trluendulfonylpropanediol(NITTP) was taken as the precursor and simpleone potmethod was used. CFN-MPS-100 fluorine multifunction radiopharmaceutical chemical synthesis module was adopted to complete the radioactive fluorination reaction in a closed flat flask, and the crude product was purified by semi-preparative HPLC, the solvent was removed by rotary evaporation. Then 15 ml saline was added into the product to get 18F-FMISO injection. Radio-HPLC and radio-TLC were applied for quality control. Results 18F-FMISO was obtained in 60 min with the radiochemical yield of (32±5.0)% (no decay corrected, n=25). The radiochemical purity was above 99.0% and still above 98.5% after 6 h. The radioactive concentration was above 1.11×1012 Bq/L. The product was colorless solution, with pH value of 7.0. The radioactive nuclear purity was more than 99%. The K222 was less than 25 μg/ml. Conclusion 18F-FMISO could be synthesized with automatic synthesis method based on the CFN-MPS-100 fluorine multifunction module. The labeling rate, stability and chemical purity are high. Key words: FMISO; Isotope labeling; Fluorine radiotopes; Chemical synthesis

More Than Telemonitoring: Health Provider Use and Nonuse of Life-Log Data in Irritable Bowel Syndrome and Weight Management.

BackgroundThe quantified self, self-monitoring or life-logging movement is a trend to incorporate technology into data acquisition on aspects of a person's daily life in terms of inputs (eg food consumed), states (eg mood), and performance (mental and physical). Consumer self-monitoring mobile phone apps have been widely studied and used to promote healthy behavior changes. Data collected through life-logging apps also have the potential to support clinical care.ObjectiveWe sought to develop an in-depth understanding of providers’ facilitators and barriers to successfully integrating life-log data into their practices and creating better experiences. We specifically investigated three research questions: How do providers currently use patient-collected life-log data in clinical practice? What are provider concerns and needs with respect to this data? What are the constraints for providers to integrate this type of data into their workflows?MethodsWe interviewed 21 health care providers—physicians, dietitians, a nurse practitioner, and a behavioral psychologist—who work with obese and irritable bowel syndrome patients. We transcribed and analyzed interviews according to thematic analysis and an affinity diagramming process.ResultsProviders reported using self-monitoring data to enhance provider-patient communication, develop personalized treatment plans, and to motivate and educate patients, in addition to using them as diagnostic and adherence tools. However, limitations associated with current systems and workflows create barriers to regular and effective review of this data. These barriers include a lack of time to review detailed records, questions about providers' expertise to review it, and skepticism about additional benefits offered by reviewing data. Current self-monitoring tools also often lack flexibility, standardized formats, and mechanisms to share data with providers.ConclusionsVariations in provider needs affect tracking and reviewing needs. Systems to support diagnosis might require better reliability and resolution, while systems to support interaction should support collaborative reflection and communication. Automatic synthesis of data logs could help providers focus on educational goals while communication of contextual information might help providers better understand patient values. We also discuss how current mobile apps and provider systems do, and do not, support these goals, and future design opportunities to realize the potential benefits of using life-logging tools in clinical care.

Interactive Sketch-Driven Image Synthesis

We present an interactive system for composing realistic images of an object under arbitrary pose and appearance specified by sketching. Our system draws inspiration from a traditional illustration workflow: The user first sketches rough ‘masses’ of the object, as ellipses, to define an initial abstract pose that can then be refined with more detailed contours as desired. The system is made robust to partial or inaccurate sketches using a reduced-dimensionality model of pose space learnt from a labelled collection of photos. Throughout the composition process, interactive visual feedback is provided to guide the user. Finally, the user's partial or complete sketch, complemented with appearance requirements, is used to constrain the automatic synthesis of a novel, high-quality, realistic image.

Two-stage continuous flow synthesis of epoxidized fatty acid methyl esters in a micro-flow system

A new protocol combining transesterification reaction with epoxidation process was reported. Besides, a novel continuous extraction device was employed in the integrated process to realize the automatic continuous flow synthesis of epoxidized fatty acid methyl esters (FAMEs). Furthermore, a capillary column containing desiccants was used in the post-processing, leading to dry product.

Abstract 3202: Single cell analysis of ascites macrophages in ovarian cancer

Abstract Macrophages compose a major part of the tumor microenvironment (TME) in several types of cancer, including ovarian cancer [1]. Studies have shown that a high percentage of tumor associated macrophages (TAMs) correlates with a poor prognosis in ovarian cancer [2], due to the crucial role of TAMs in promoting tumor growth and angiogenesis [3,4]. Yet not much investigation has been executed to reveal the function of macrophages in ovarian cancer ascites, a hallmark of ovarian cancer. Previous gene expression analysis in TAMs often used bulk samples [5,6]. However, due to the complexity of the peritoneal environment, this approach had the effect of “dampening” rare and potentially informative signals from a heterogeneous population such as ascites macrophages. Therefore, we resorted to single-cell expression analysis to dissect the heterogeneity of ascites macrophages. Recent breakthroughs in single cell RNA-seq techniques have made it more cost effective to process a large number of samples at single cell resolutions. Here we used Fluidigm's Single-Cell Auto Prep System, a state-of-art technology for automate single cell cDNA synthesis [7]. We sequenced single ascites macrophages from ID8 murine ovarian cancer model and single alternatively activated bone marrow derived macrophages (BMDM-M2). When comparing the single cell expression profiles of ascites macrophages to BMDM using principle component analysis (PCA), we observed that the ascites macrophages scattered broadly and could be further divided into two groups, whereas BMDM were tightly clustered into one group. Furthermore, gene oncology (GO) analysis of highly expressed genes in each group revealed that ascites macrophages had a distinct gene expression profile from BMDM, highlighting the metabolic pathways, especially catabolic process. We are currently working on validating these findings in human patients with ovarian carcinoma. In summary, this work sheds light on the understanding of the role of ascites macrophages in ovarian cancer. 1. Qian BZ, Pollard JW. Cell. 2010;141:39-51. 2. He YF, Zhang MY, Wu X, et al. PLoS One. 2013;8:e79769. 3. Mantovani A, Germano G, Marchesi F, et al. Eur J Immunol 2011;41:2522-25. 4. Murray PJ, Wynn TA. Nat Rev Immunol, 2011;11:723-37. 5. The Cancer Genome Atlas Research Network. Nature. 2014;511:543-50. 6. The Cancer Genome Atlas Research Network. Nature. 2014;513:202-9. 7. Wu AR, Neff NF, Kalisky T, et al. Nat Methods. 2014;11:41-6. Citation Format: Huanhuan Mahsa He, Feiqiao Brian Yu, Stephen R. Quake, Oliver Dorigo. Single cell analysis of ascites macrophages in ovarian cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3202. doi:10.1158/1538-7445.AM2015-3202

Automatic synthesis of communication and concurrency for exploring component-based system implementations considering UML channel semantics

Nowadays, multi-processor systems play a critical role in embedded system engineering. As a result, the generation of optimal concurrent implementations is an unavoidable but difficult task. Correct concurrent codes achieving maximum performance on the target platform are hard to obtain. On the one hand, dependencies on concurrent computations, such as shared variables or synchronizations, are extremely difficult to analyze from source code. On the other hand, it is completely unfeasible for designers to manually generate multiple implementations in order to evaluate and compare all the possible design alternatives. To overcome these limitations, this paper presents an automatic code generation approach focusing on communication channel semantics. The approach proposes the use of UML/MARTE models to enable designers to graphically handle dependencies and concurrency of the models. As a result, the automatic generation process enables multiple design alternatives to be easily obtained and evaluated without adding manual effort to the design process. To demonstrate these capabilities, the methodology is tested with two large examples.

On Promptness in Parity Games*†

Parity games are a powerful formalism for the automatic synthesis and verification of reactive systems. They are closely related to alternating ω-automata and emerge as a natural method for the solution of the μ-calculus model checking problem. Due to these strict connections, parity games are a well-established environment to describe liveness properties such as “every request that occurs infinitely often is eventually responded”. Unfortunately, the classical form of such a condition suffers from the strong drawback that there is no bound on the effective time that separates a request from its response, i.e., responses are not promptly provided. Recently, to overcome this limitation, several parity game variants have been proposed, in which quantitative requirements are added to the classic qualitative ones.

First Results From the Phenology-Based Synthesis Classifier Using Landsat 8 Imagery

A fully automatic phenology-based synthesis (PBS) classification algorithm was developed to map land cover based on medium spatial resolution satellite data using the Google Earth Engine cloud computing platform. Vegetation seasonality, particularly in the tropical dry regions, can lead conventional algorithms based on a single date image classification to “misclassify” land cover types, as the selected date might reflect only a particular stage of the natural phenological cycle. The PBS classifier operates with occurrence rules applied to a selection of single date image classifications of the study area to assign the most appropriate land cover class. Since the launch of Landsat 8 in 2013, it has been possible to acquire imagery at any point on the Earth every 16 days with exceptional radiometric quality. The relatively high global acquisition frequency and the open data policy allow near-real-time land cover mapping and monitoring with automated tools such as the PBS classifier. We mapped four protected areas and their 20-km buffer zones from different ecoregions in Sub-Saharan Africa using the PBS classifier to present its first results. Accuracy assessment was carried out through a visual interpretation of very high resolution images using a Web geographic information system interface. The combined overall accuracy was over 90%, which demonstrates the potential of the classifier and the power of cloud computing in geospatial sciences.

Fully-automated synthesis of 16β-18F-fluoro-5α-dihydrotestosterone (FDHT) on the ELIXYS radiosynthesizer

Noninvasive in vivo imaging of androgen receptor (AR) levels with positron emission tomography (PET) is becoming the primary tool in prostate cancer detection and staging. Of the potential 18F-labeled PET tracers, 18F-FDHT has clinically shown to be of highest diagnostic value. We demonstrate the first automated synthesis of 18F-FDHT by adapting the conventional manual synthesis onto the fully-automated ELIXYS radiosynthesizer. Clinically-relevant amounts of 18F-FDHT were synthesized on ELIXYS in 90min with decay-corrected radiochemical yield of 29±5% (n=7). The specific activity was 4.6Ci/µmol (170GBq/µmol) at end of formulation with a starting activity of 1.0Ci (37GBq). The formulated 18F-FDHT yielded sufficient activity for multiple patient doses and passed all quality control tests required for routine clinical use.

Automatic synthesis of RF front-end blocks using multi-objective evolutionary techniques

Typically the design of a Radio-Frequency (RF) circuit is difficult, time-consuming and often based around an iterative process. In this manuscript, an automatic synthesis of three typical blocks of nowadays RF front-end receivers, a narrowband differential low-noise amplifier, a mixer and a local oscillator, is presented. The synthesis of the three circuits was made at sizing level and was carried out by Analog IC Design Automation (AIDA). AIDA is a multi-objective multi-constraint simulator based automatic IC design tool, which optimizes analog circuits through the usage of evolutionary computation. The performance potential of the circuits and tool is evaluated through electrical simulation results, which are finally compared with recently published state-of-the-art works, with overall better results and little time-consumption, proving the surplus value of using an automatic IC design tool in RF circuitry synthesis.

Psychopathology of Lived Time: Abnormal Time Experience in Persons With Schizophrenia.

Abnormal time experience (ATE) in schizophrenia is a long-standing theme of phenomenological psychopathology. This is because temporality constitutes the bedrock of any experience and its integrity is fundamental for the sense of coherence and continuity of selfhood and personal identity. To characterize ATE in schizophrenia patients as compared to major depressives we interviewed, in a clinical setting over a period of 15 years, 550 consecutive patients affected by schizophrenic and affective disorders. Clinical files were analyzed by means of Consensual Qualitative Research (CQR), an inductive method suited to research that requires rich descriptions of inner experiences. Of the whole sample, 109 persons affected by schizophrenic (n = 95 acute, n = 14 chronic) and 37 by major depression reported at least 1 ATE. ATE are more represented in acute (N = 109 out of 198; 55%) than in chronic schizophrenic patients (N = 14 out of 103; 13%). The main feature of ATE in people with schizophrenia is the fragmentation of time experience (71 out of 109 patients), an impairment of the automatic and prereflexive synthesis of primal impression-retention-protention. This includes 4 subcategories: disruption of time flowing, déjà vu/vecu, premonitions about oneself and the external world. We contrasted ATE in schizophrenia and in major depression, finding relevant differences: in major depressives there is no disarticulation of time experience, rather timelessness because time lacks duration, not articulation. These core features of the schizophrenic pheno-phenotype may be related to self-disorders and to the manifold of characteristic schizophrenic symptoms, including so called bizarre delusions and verbal-acoustic hallucinations.

Automatic Synthesis of Comparator Circuit Using Genetic Algorithm and SPICE Optimizing Function

This Paper Describes our Challenge of Automatic Analog Circuit Design by Focusingon a Comparator Circuit which is One of the Important Analog Building Blocks. the Geneticalgorithm Chooses the Optimal Circuit Topology and HSPICE Optimizing Function Obtains Theiroptimal Parameter Values Automatically. Automatic Design for Analog Circuit has Not Beenrealized yet, even though Automatic Design is being Used in Digital Circuit Design; the Reasonbehind this is that the Number of Parameters to Be Considered in an Analog Circuit Designis much Larger than Digital Circuit Design. Nowadays it is Extremely Difficult to Design Icsmanually due to their Large Scale Integration and Hence their Automatic Design is Demanded. Wepresent our Automatic Circuit Design Owchart Programmed with Java Language which Realizes1-Click Automatic Synthesis of the Comparator, and Shows that our Method can Obtain a Betterperformance Comparator Compared to an Initially-Set Comparator.

Use of graphics processing units for automatic synthesis of programs

Genetic programming (GP) is an evolutionary method that allows computers to solve problems automatically. However, the computational power required for the evaluation of billions of programs imposes a serious limitation on the problem size. This work focuses on accelerating GP to support the synthesis of large problems. This is done by completely exploiting the highly parallel environment of graphics processing units (GPUs). Here, we propose a new quantum-inspired linear GP approach that implements all the GP steps in the GPU and provides the following: (1) significant performance improvements in the GP steps, (2) elimination of the overhead of copying the fitness results from the GPU to the CPU, and (3) incorporation of a new selection mechanism to recognize the programs with the best evaluations. The proposed approach outperforms the previous approach for large-scale synthetic and real-world problems. Further, it provides a remarkable speedup over the CPU execution.

Towards closing the specification gap by integrating algorithm-level and system-level design

Modern multiprocessor system-on-chip (MPSoC) designs face challenges in tremendous complexity imposed by the wide range of functional and architectural requirements. Design automation methodologies address some of the complexity through design abstractions from two different angles, namely functionality and architecture. Algorithm-level design (ALD), such as Simulink, focuses on managing the functional complexity through algorithm modeling. Meanwhile, system-level design (SLD) addresses the platform complexity by exploring and synthesizing architecture models from specifications captured in a system-level design language (SLDL). However, these two design methodologies are inherently disjoint as they focus on different design domains at separate abstraction levels. As a result, transition from algorithm models to system-level explorations often requires re-authoring of the functional SLDL specification to expose hierarchy and parallelism. This thus forms the Specification Gap causing a loss of productivity and stalling the overall design cycle. This paper proposes to join ALD and SLD to close the specification gap through a Specification Synthesis approach. We introduce Algo2Spec, which synthesizes an SLDL specification out of an algorithm model in Simulink. Algo2Spec enables a rapid heterogeneous Design Space Exploration while still tuning the algorithm according to functional needs. With Algo2Spec, system level design principles propagate up to higher abstraction levels and a new joint algorithm/architecture co-design flow is created. The joint flow seamlessly spans from algorithm modeling down to heterogeneous implementations crossing multiple abstractions. Our approach empowers designers to create, simulate, and explore models in a rapid design cycle. Utilizing the joint flow, we demonstrate opportunities for algorithm and architecture co-design on a set of real-world benchmark applications ranging from 57 to 5733 Simulink blocks. The automatic synthesis avoids the tedious and error-prone manual conversion of Simulink algorithm models into SLDL specifications. Algo2Spec executes in 4.5 s on average to synthesize a single Simulink block to a fully functional SLDL behavior. Compared to an estimated 5.18 h of manual editing, Algo2Spec improves productivity by three orders of magnitude for obtaining the system-level specifications from Simulink models.

Impact of residual 18F-fluoride in 18F-FDOPA for the diagnosis of neuroblastoma

PET imaging with (18)F-FDOPA has been successfully applied in the diagnosis and surveillance of neuroblastoma (NB) by targeting the overexpression of aromatic L-amino acid decarboxylase. This study aims to assess the impact of residual (18)F-fluoride on (18)F-FDOPA PET in NB and to implement a method to maintain low (18)F-fluoride content in future studies. Automatic synthesis of (18)F-FDOPA was based on the electrophilic method using TRACERlab FXFE module. Radio-TLC was employed to determine residual (18)F-fluoride levels. We analyzed the impact of residual (18)F-fluoride on the images of 35 patients undergoing (18)F-FDOPA PET at initial diagnosis and/or follow-ups of NB. In 35 batches of (18)F-FDOPA products from 9/28/2010 to 07/27/2011, the mean residual (18)F-fluoride level was 4.4% (range 0.2-19.1%). Residual (18)F-fluoride level ≥4.0% was associated with dense uptake in the growth plates, skull, and pelvis on PET scans, which may interfere with the interpretation of (18)F-FDOPA imaging in NB. By applying stringent restraints in (18)F-FDOPAproduction, including regular renewal of reagents, exclusive use of NH4OH, and timely replacement of HPLC column, the incidence of (18)F-FDOPA batches with residual (18)F-fluoride level ≥4.0% was reduced from 33 to 4% (P<0.0001) during 7/30/2011-4/29/2013. By monitoring residual (18)F-fluoride levels and keeping stringent restraint procedures, low (18)F-fluoride content was achieved in most batches of (18)F-FDOPA, which diminished false-positive skeletal uptake. An appropriate upper limit of (18)F-fluoride level is suggested to be included in the criteria of routine quality control of (18)F-FDOPA productions.

Preliminary Study of Brain Glucose Metabolism Changes in Patients with Lung Cancer of Different Histological Types

Background:Cerebral glucose metabolism changes are always observed in patients suffering from malignant tumors. This preliminary study aimed to investigate the brain glucose metabolism changes in patients with lung cancer of different histological types.Methods:One hundred and twenty patients with primary untreated lung cancer, who visited People's Hospital of Zhengzhou University from February 2012 to July 2013, were divided into three groups based on histological types confirmed by biopsy or surgical pathology, which included adenocarcinoma (52 cases), squamous cell carcinoma (43 cases), and small-cell carcinoma (25 cases). The whole body 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT) of these cases was retrospectively studied. The brain PET data of three groups were analyzed individually using statistical parametric maps (SPM) software, with 50 age-matched and gender-matched healthy controls for comparison.Results:The brain resting glucose metabolism in all three lung cancer groups showed regional cerebral metabolic reduction. The hypo-metabolic cerebral regions were mainly distributed at the left superior and middle frontal, bilateral superior and middle temporal and inferior and middle temporal gyrus. Besides, the hypo-metabolic regions were also found in the right inferior parietal lobule and hippocampus in the small-cell carcinoma group. The area of the total hypo-metabolic cerebral regions in the small-cell carcinoma group (total voxel value 3255) was larger than those in the adenocarcinoma group (total voxel value 1217) and squamous cell carcinoma group (total voxel value 1292).Conclusions:The brain resting glucose metabolism in patients with lung cancer shows regional cerebral metabolic reduction and the brain hypo-metabolic changes are related to the histological types of lung cancer.

Decentralizing SDN Policies

Software-defined networking (SDN) is a new paradigm for operating and managing computer networks. SDN enables logically-centralized control over network devices through a "controller" --- software that operates independently of the network hardware. Network operators can run both in-house and third-party SDN programs on top of the controller, e.g., to specify routing and access control policies. In practice, having the controller handle events limits the network scalability. Therefore, the feasibility of SDN depends on the ability to efficiently decentralize network event-handling by installing forwarding rules on the switches. However, installing a rule too early or too late may lead to incorrect behavior, e.g., (1) packets may be forwarded to the wrong destination or incorrectly dropped; (2) packets handled by the switch may hide vital information from the controller, leading to incorrect forwarding behavior. The second issue is subtle and sometimes missed even by experienced programmers. The contributions of this paper are two fold. First, we formalize the correctness and optimality requirements for decentralizing network policies. Second, we identify a useful class of network policies which permits automatic synthesis of a controller which performs optimal forwarding rule installation.

Parameter evaluation and fully-automated radiosynthesis of [11C]harmine for imaging of MAO-A for clinical trials

The aim of the present study was the evaluation and automation of the radiosynthesis of [11C]harmine for clinical trials. The following parameters have been investigated: amount of base, precursor concentration, solvent, reaction temperature and time. The optimum reaction conditions were determined to be 2–3mg/mL precursor activated with 1eq. 5M NaOH in DMSO, 80°C reaction temperature and 2min reaction time. Under these conditions 6.1±1GBq (51.0±11% based on [11C]CH3I, corrected for decay) of [11C]harmine (n=72) were obtained. The specific activity was 101.32±28.2GBq/µmol (at EOS). All quality control parameters were in accordance with the standards for parenteral human application. Due to its reliability and high yields, this fully-automated synthesis method can be used as routine set-up.