OBJECTIVES/GOALS: The 'field effect' is a concept in pathology that pre-malignant tissue changes forecast health. Spatial transcriptomics could detect these changes earlier than histopathology, suggesting new early cancer screening methods. Knowing how normal tissue damage relates to cancer’s origin and progression may improve long-term outcomes. METHODS/STUDY POPULATION: We trained DEGAS, our machine learning framework, with prostate cancer data, combining both general cancer patterns and in-depth genetic information from individual tumors. The Tumor Cancer Genome Atlas (TCGA) shows how gene patterns in tumors relate to patient outcomes, emphasizing the differences between tumors from different patients (intertumor). On the other hand, spatial transcriptomics (ST) shows the genetic variety within a single tumor (intratumor) but has limited samples, making it hard to know which genetic differences are important for treatment. DEGAS bridges these areas by finding tissue sections that resemble those in TCGA profiles and are key indicators of patient survival. DEGAS serves as a valuable tool for generating clinically-important hypotheses. RESULTS/ANTICIPATED RESULTS: DEGAS identified benign-appearing glands in a normal prostate as being highly associated with poor progression-free survival. These glands have transcriptional signatures similar to high-grade prostate cancer. We confirmed this finding in a separate prostate cancer ST dataset. By integrating single cell (SC) data we demonstrated that cells annotated as cancerous in the SC data map to regions of benign glands in the ST dataset. We pinpoint several genes, chiefly Microseminoprotein-β (MSMB, PSP94), where reduced expression is highly correlated with poor progression-free survival. Cell type specific differential expression analysis further revealed that loss of MSMB expression associated with poor outcomes occurs specifically in luminal epithelia, the putative progenitor of prostate cancer. DISCUSSION/SIGNIFICANCE: DEGAS reveals that normal-appearing tissue can be highly-associated with tumor progression and underscores the importance of the 'field effect' in cancer research. Traditional analysis may miss such nuance, hiding key transitional cell states. Validating gene markers could boost early cancer detection and understanding of metastasis.

The iron-rich calcareous soil (Typic Rhodustalf) from the Penghu island group represents a volcanic area. The black soils (Typic Haplustert, Vertic Endoaquoll, Typic Hapludolls) are typical of eastern Taiwan. Four A horizons and a pedon from the iron-rich calcareous soil and four pedons from the black soils were studied to analyze soil properties and clay compositions. The objective was to compare the properties of smectites developed from different parent materials. The materials were studied by using conventional X-ray diffraction (XRD) of K- and Mg-saturated clays and involved the alkylam-monium (C = 12) method and the Greene-Kelly test. The mean-layer charge of smectites (0.48–0.52 cmol(c)/O10(OH)2) in the iron-rich calcareous soil was found to be higher than the black soils (0.43–0.48 cmol(c)/O10(OH)2). A smectite of higher charge developed from the basalts. This smectite is enriched in Fe and Mg, and lacks Si, thereby forming beidellite and/or nontronite. In contrast, under high precipitation, elevated temperature, base saturation (e.g., Na, K, Ca, Mg), and about equal wet and dry cycles per year in the black soil environments, smectites developed from the complicated geologic site of eastern Taiwan. These smectites transformed to smectite-kaolinite mixed-layer clay and thus, resulted in lower-charge smectites. The K fixation capacity of the iron-rich calcareous soil was higher than the black soils.

OBJECTIVES/GOALS: Single-cell and spatial transcriptomics have revealed high heterogeneity in the tumor and microenvironment. Identifying populations of cells that impact a patient’s prognosis is an important research goal, so researchers can generate hypotheses and clinicians can provide targeted treatment. METHODS/STUDY POPULATION: DEGAS uses deep-transfer-learning to identify patterns between patient tumor RNA-seq and clinical outcomes and map these associations on to higher-resolution data like spatial and single-cell transcriptomics. We apply DEGAS to prostate and pancreatic cancer spatial transcriptomics samples, as well as one normal sample of prostate tissue. We used the TCGA prostate cancer cohort to with the accompanying survival information and publicly accessible prostate cancer ST data from 10X Genomics to predict survival associations in the ST slides derived from the TCGA patients. Based on these survival associations, we identify higher risk subsections of ST slides which can be further studied. RESULTS/ANTICIPATED RESULTS: We were able to validate our method by comparing it to Scissor and were able to show that the number of high-risk regions in prostate cancer slides increased with the stage of disease. Furthermore, we identify transcriptomic signatures enriched for ontology terms associated with growth regulation and apoptosis, inflammation, immune signaling, and autophagy in histologically normal prostate tissues and adjacent normal pancreatic cancer tissues that were identified as high-risk by DEGAS. The regions highlighted by DEGAS could reflect transcriptional precursors to intraepithelial neoplasia–a well-recognized premalignant morphological change in glandular epithelium. DISCUSSION/SIGNIFICANCE: Identifying biomarkers of tissue stress that precede morphologic diagnosis of high-grade pre-malignant lesions by a pathologist may help triage patients at high risk for future development of cancer, or aid in better understanding whether histologically normal pre-malignant tissues at tumor margins contribute to recurrence.

A high image rejection 38 GHz demodulator in TSMC 65-nm CMOS process is presented. To achieve better than −40 dBc image rejection ratio (IRR), a low I/Q mismatch 45° LO power splitter of sub-harmonic mixer is proposed. In this design, the 45° LO power splitter is composed of a Wilkinson divider, a series delay line with electrical length of 45° on one side of the divider, and a shunt 90° transmission line on the other side. This configuration is attractive because of its design simplicity and easy fabrication. Compared with the conventional techniques that utilize capacitors and inductors instead of the shunt 90° transmission line, the proposed LO power splitter can alleviate the issue of process variation. The demodulator demonstrates an IRR lower than −40 dBc from 37.5 to 41.5 GHz. In addition, conversion gain is 1.3 ± 0.9 dB from 33 to 41 GHz with 6 dBm LO power. The total direct current power consumption is 78 mW from 1.0 V supply voltage. At the modulation scheme of 4096-QAM, the proposed demodulator demonstrates 1.7% (−35.1 dB) error vector magnitude (EVM), which is very close to the EVM measurement floor 1.6% (−36 dB) of our millimeter-wave signal analyzer.

A force sensorless impedance controller is proposed in this paper for robot manipulators without using force estimators. From the observation of the impedance control law, the force feedback term can be canceled if the inertia matrix in the target impedance is the same as the robot inertia matrix. However, the inertia matrix in the target impedance is almost always a constant matrix, while the robot inertia matrix is a function of the robot configuration, and hence, they may not be identical in general. A modification of the coefficient matrix for the contact force term in the target impedance is suggested in this paper to enable cancelation of the force feedback term in the impedance control law so that a force sensorless impedance controller without using force estimators can be obtained. The tracking performance in the free space phase and the motion trajectory in the compliant motion phase of the new design are almost the same as those in the traditional impedance control. Modification of the inertia matrix in the target impedance will result in small variations of the contact force which is acceptable in practical applications. For robot manipulators containing uncertainties, an adaptive version of the new controller is also developed in this paper to give satisfactory performance without the need for force sensors. Rigorous mathematical justification in closed-loop stability is given in detail, and computer simulations are performed to verify the efficacy of the proposed design.

While information exchange is essential in the policy process, little is known about how divergent subgroups filter actors’ technical and political information exchange, blocking learning processes. Guided by social identity, group entitativity, and self-categorisation theories, we introduce the concept and measurement of identity-based subgroups referring to informal clusters shaped by the self-referent perception of similarities among actors. The identity-based subgroup is recognised as a precursor for coalition building in a policy subsystem but received inadequate attention in the research on Advocacy Coalition Framework. We examine how divergent identity-based subgroups moderate the links between relational embeddedness and technical/political information exchanges in an adversarial fracking policy network in New York. Our quadratic assignment procedure multiple regression indicated that, despite trust, policy actors from different identity-based subgroups are less likely to share technical and political information in the network. When two actors’ identity-based subgroups are different, competition is more likely associated with lower technical information exchange in the network. These findings extend research on information exchange in adversarial policy subsystems.

The nutritional status experienced in the early development of life plays a vital role in the long-term metabolic state of the individual, which is known as nutritional programming. The present study investigated the long-term effects of vegetable oil (VO) nutritional programming during the early life of large yellow croaker. First, larvae were fed either a fish oil (FO) diet or a VO diet for 30 d. Subsequently, under the same conditions, all fish were fed a commercial diet for 90 d and thereafter challenged with an FO or VO diet for 30 d. The results showed that growth performance was significantly lower in larvae fed the VO diet than in those in fed the FO diet in the stimulus phase. Notably, VO nutritional history fish showed lower levels of liver lipids liver total triglycerides and serum nonesterified free fatty acids than the FO nutritional history fish when juveniles were challenged with the VO diet, which was consistent with the expression of lipogenesis-related genes and proteins. Moreover, the VO nutritional history fish showed lower liver damage and higher antioxidant capacity than FO nutritional history fish when challenged with the VO diet. In summary, this study showed that a short VO stimulus during the early life stage of large yellow croaker, had a long-term effect on lipid metabolism and the antioxidant system. Specifically, VO nutritional programming had a positive effect on alleviating abnormal lipid deposition on the liver, liver damage, and the reduction of hepatic antioxidant capacity caused by a VO diet.

We have proposed and experimentally demonstrated a novel scheme for efficient mid-infrared difference-frequency generation based on passively synchronized fiber lasers. The adoption of coincident seeding pulses in the nonlinear conversion process could substantially lower the pumping threshold for mid-infrared parametric emission. Consequently, a picosecond mid-infrared source at 3.1 μm was prepared with watt-level average power, and a maximum power conversion efficiency of 77% was realized from pump to down-converted light. Additionally, the long-term stability of generated power was manifested with a relative fluctuation as low as 0.17% over one hour. Thanks to the all-optical passive synchronization and all-polarization-maintaining fiber architecture, the implemented laser system was also featured with simplicity, compactness and robustness, which would favor subsequent applications beyond laboratory operation.

Sugarcane brown rust, caused by Puccinia melanocephala, is one of the main diseases of sugarcane in China. The identification and discovery of new resistance genes have important theoretical and practical significance for preventing outbreaks of brown rust and ensuring the sustainable production of sugarcane. To screen for polymorphic simple-sequence repeat (SSR) molecular markers for localization of brown rust resistance genes, we used two populations that are suitable for genetic linkage map construction and mapping of new resistance genes to construct resistant and susceptible genetic pools. We then screened 449 pairs of primers to identify polymorphic SSR markers in the parental lines and the resistant/susceptible genetic pools. The results showed that 25 pairs of primers directed amplification of polymorphic DNA fragments between the parents of the cross combination ‘Yuetang 03-393’ × ‘ROC 24’, and 16 pairs of primers amplified polymorphic fragments between the parents of the cross combination ‘Liucheng 03-1137’ × ‘Dezhe 93-88’. Four pairs of primers (SMC236CG, SCESSR0928, SCESSR0636 and SCESSR2551) amplified polymorphic DNA fragments between the parental lines and the resistant/susceptible genetic pools in ‘Yuetang 03-393’ × ‘ROC 24’. The results of this study will establish a solid foundation for the mapping of new brown rust resistance genes, genetic linkage map construction and the development of closely-associated molecular markers in sugarcane.

Solid solution 0.94Na0.5Bi0.5TiO3–6BaTiO3 (NBT–6BT) is considered to be one kind of lead-free piezoelectric materials with excellent electrical properties due to the existence of morphotropic phase boundary (MPB). However, its relatively lower depolarization temperature is a long-standing bottleneck for the application of NBT-based piezoelectric ceramics. In this work, the influence of thermal quenching on depolarization temperature and electrical properties of rare-earth Ho-doped NBT–6BT lead-free ceramics was investigated. It was shown that the relative high piezoelectric performance, as well as an improvement of depolarization temperature (Td), can be realized by thermal quenching. The results showed that the quenching process induced high concentration of oxygen vacancy, giving rise to the change of octahedra mode and enhanced lattice distortion, which is benefit to the temperature stability of piezoelectric and ferroelectric properties. Furthermore, up-conversion photoluminescence (PL) of Ho-doped NBT–6BT could be effectively tuned by the introduction of oxygen vacancy, suggesting a promising potential in optical–electrical multifunctional devices.

We assessed inheritance of resistance to sugarcane brown rust (Puccinia melanocephala) in selfing F1 populations of wild sugarcane germplasm Erianthus rockii ‘Yundian 95-19’ and E. rockii ‘Yundian 95-20’. We tested parent and selfing F1 individuals for the brown rust resistance gene, Bru1, that has been shown to confer resistance to brown rust in sugarcane. The Bru1 gene was not detected in E. rockii ‘Yundian 95-19’, E. rockii ‘Yundian 95-20’ or their selfing F1 individuals, and we found there was segregation of resistance in the two selfing F1 populations (segregation ratio: 3:1). The results confirmed resistance in E. rockii ‘Yundian 95-19’ and E. rockii ‘Yundian 95-20’ to sugarcane brown rust is controlled by a novel, single dominant gene.

Fe therapy can be effective in heart failure patients both with and without anaemia. However, the role of Fe therapy in such patients is still uncertain. In this review, the aim was to evaluate the efficacy and safety of Fe therapy in adult patients with heart failure who have reduced ejection fraction (HFrEF). Multiple databases (PubMed, Medline, EMBASE, the Cochrane Library and Clinical Trials) were searched up to December 2017 and the reference lists of relevant articles obtained from the search were reviewed. Data extracted from randomised control trials (RCT) selected for the review were pooled using a fixed effects model or a random effects model, according to heterogeneity between trials. Nine RCT were included in this meta-analysis which included a total of 789 patients who received Fe therapy and who in turn were compared with 585 controls. There was significant improvement in the 6-min walk test (19·05 m, 95 % CI 10·48, 27·62) and peak VO2/kg (0·93 ml/kg per min, 95 % CI 0·16, 1·69) in the Fe supplementation arm. With Fe therapy, fewer patients were hospitalised for heart failure (OR: 0·42, 95 % CI 0·27, 0·65), but no relationship was found for total re-hospitalisation (OR: 0·70, 95 % CI 0·32, 1·51) or mortality (OR: 0·70, 95 % CI 0·38, 1·28). Fe therapy has the potential to improve exercise tolerance, reduce re-hospitalisations for patients with HFrEF having Fe deficiency. In addition, Fe supplementation was found to be safe, with no increased rate of adverse events.

Globally, the prevalence of childhood obesity has substantially increased at an alarming rate. This study investigated associations between dietary patterns and overweight/obesity in 3- to 6-year-old children. Recruited children were from four prefecture-level cities in Eastern China. Childhood overweight and obesity were defined according to WHO Child Growth Standards. Individual dietary patterns were assessed by a comprehensive self-administered FFQ using thirty-five food items. Using factor analysis two dietary patterns were derived: the traditional Chinese pattern was characterised by high consumption of cereals, vegetables and fresh juices while the modern pattern was characterised by high consumption of Western fast food, Chinese fast food, sweets/sugary foods and carbonated beverages. The associations of dietary patterns with overweight/obesity were evaluated by logistic regression models. Data of 8900 preschool children from thirty-five kindergartens recruited from March to June 2015 were used in the final analysis. Adherence to the modern dietary pattern was positively associated with children's age while adherence to the traditional dietary pattern was positively associated with maternal education; these associations were statistically significant. After adjustment, we found that being in the highest tertile of any identified dietary patterns was not significantly associated with overweight and obesity. Dietary patterns are not associated with overweight/obesity in Chinese preschool children. Prospective studies are needed to establish a causal link between dietary patterns and childhood obesity.

Blue-ice areas (BIAs) and their geographical distribution in Antarctica were mapped using Landsat-7 ETM+ images with 15 m spatial resolution obtained during the 1999–2003 austral summers and covering the area north of 82.5° S, and a snow grain-size image of the MODIS-based Mosaic of Antarctica (MOA) dataset with 125 m grid spacing acquired during the 2003/04 austral summer from 82.5°S to the South Pole. A map of BIAs was created with algorithms of thresholds based on band ratio and reflectance for ETM+ data and thresholds based on snow grain size for the MOA dataset. The underlying principle is that blue ice can be separated from snow or rock by their spectral discrepancies and by different grain sizes of snow and ice. We estimate the total area of BIAs in Antarctica during the data acquisition period is 234 549 km2, or 1.67% of the area of the continent. Blue ice is scattered widely over the continent but is generally located in coastal or mountainous regions. The BIA dataset presented in this study is the first map covering the entire Antarctic continent sourced solely from ETM+ and MODIS data. This dataset can potentially benefit other studies in glaciology, meteorology, climatology and paleoclimate, meteorite collection and airstrip site selection.

Climate change during the Quaternary played an important role in the distribution of extant plants. Herein, cone scales of Cedrus (Pinaceae) were uncovered from the Upper Pliocene Sanying Formation, Longmen Village, Yongping County of Yunnan Province in southwestern China. Detailed comparisons show that these fossils all belong to the genus Cedrus (Pinaceae), and a new species is proposed, Cedrus angusta sp. nov. This find expands the known distribution of Cedrus during the Late Pliocene to Yunnan, where the genus no longer exists in natural forests. Based on the analysis of reconstructed Neogene climate data, we suggest that the intensification of the East Asian winter monsoon during the Quaternary may have dramatically increased seasonality and given rise to a much drier winter in Yunnan. Combined with information on Cedrus fossil records and its seed physiology, we conclude that the intensification of a drier climate after the Late Pliocene may have prevented the survival of Cedrus seedlings, leading to the eventual disappearance of Cedrus in western Yunnan. This study indicates that the topography in southwestern China acted as a vital refuge for many plants during the Quaternary, but that other species gradually disappeared due to the intensification of the monsoonal climate.