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1
Keilson, J., and M. Zachmann. "Homogeneous row-continuous bivariate markov chains with boundaries." Journal of Applied Probability 25, A (1988): 237–56. http://dx.doi.org/10.2307/3214160.
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The matrix-geometric results of M. Neuts are extended to ergodic row-continuous bivariate Markov processes [J(t), N(t)] on state space B = {(j, n)} for which: (a) there is a boundary level N for N(t) associated with finite buffer capacity; (b) transition rates to adjacent rows and columns are independent of row level n in the interior of B. Such processes are of interest in the modelling of queue-length for voice-data transmission in communication systems.One finds that the ergodic distribution consists of two decaying components of matrix-geometric form, the second induced by the finite buffer capacity. The results are obtained via Green's function methods and compensation. Passage-time distributions for the two boundary problems are also made available algorithmically.
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Keilson, J., and M. Zachmann. "Homogeneous row-continuous bivariate markov chains with boundaries." Journal of Applied Probability 25, A (1988): 237–56. http://dx.doi.org/10.1017/s0021900200040390.
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The matrix-geometric results of M. Neuts are extended to ergodic row-continuous bivariate Markov processes [J(t), N(t)] on state space B = {(j, n)} for which: (a) there is a boundary level N for N(t) associated with finite buffer capacity; (b) transition rates to adjacent rows and columns are independent of row level n in the interior of B. Such processes are of interest in the modelling of queue-length for voice-data transmission in communication systems. One finds that the ergodic distribution consists of two decaying components of matrix-geometric form, the second induced by the finite buffer capacity. The results are obtained via Green's function methods and compensation. Passage-time distributions for the two boundary problems are also made available algorithmically.
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Adler, André. "Limit theorems for randomly selected adjacent order statistics from a Pareto distribution." International Journal of Mathematics and Mathematical Sciences 2005, no. 21 (2005): 3427–41. http://dx.doi.org/10.1155/ijmms.2005.3427.
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Consider independent and identically distributed random variables{Xnk, 1≤k≤m, n≥1}from the Pareto distribution. We randomly select two adjacent order statistics from each row,Xn(i)andXn(i+1), where1≤i≤m−1. Then, we test to see whether or not strong and weak laws of large numbers with nonzero limits for weighted sums of the random variablesXn(i+1)/Xn(i)exist, where we place a prior distribution on the selection of each of these possible pairs of order statistics.
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Wu, Pu, Zepeng Li, Zehui Shao, and Seyed Mahmoud Sheikholeslami. "Trees with equal Roman {2}-domination number and independent Roman {2}-domination number." RAIRO - Operations Research 53, no. 2 (March 6, 2019): 389–400. http://dx.doi.org/10.1051/ro/2018116.
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A Roman {2}-dominating function (R{2}DF) on a graph G =(V, E) is a function f : V → {0, 1, 2} satisfying the condition that every vertex u for which f(u) = 0 is adjacent to either at least one vertex v with f(v) = 2 or two vertices v1, v2 with f(v1) = f(v2) = 1. The weight of an R{2}DF f is the value w(f) = ∑u∈Vf(u). The minimum weight of an R{2}DF on a graph G is called the Roman {2}-domination number γ{R2}(G) of G. An R{2}DF f is called an independent Roman {2}-dominating function (IR{2}DF) if the set of vertices with positive weight under f is independent. The minimum weight of an IR{2}DF on a graph G is called the independent Roman {2}-domination number i{R2}(G) of G. In this paper, we answer two questions posed by Rahmouni and Chellali.
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MITSUSHIO, Masaru, and Toshifumi YOSHIDOME. "Development of a Gold-deposited Square Glass Rod Sensor Capable of Independent and Simultaneous Measurements on Two Adjacent Faces." BUNSEKI KAGAKU 71, no. 4.5 (April 5, 2022): 261–67. http://dx.doi.org/10.2116/bunsekikagaku.71.261.
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Cabral, Oscar Manuel de Jesús Vera, Eduardo da Silva Lopes, Carla Krulikowski Rodrigues, and Afonso Figueiredo Filho. "Impact of Distance between Strip Roads on Productivity and Costs of a Forwarder in Commercial Thinning of Pinus Taeda Stands." Croatian journal of forest engineering 41, no. 2 (April 8, 2020): 243–49. http://dx.doi.org/10.5552/crojfe.2020.592.
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Demand for higher value-added wood products stimulates research for new, mainly mechanized, thinning operations in order to increase productivity and reduce production costs. In this context, the aim of this study was to evaluate the impact of distance between strip roads on forwarder productivity and costs of thinning operations in Pinus taeda stands. The study was carried out in 10-year-old Pinus taeda stands located in Parana State, Brazil. Two thinning methods were evaluated: (1) TH5: systematic harvest in every fifth tree row and selective harvest in adjacent rows; and (2) TH7: systematic harvest in every seventh tree row and selective harvest in adjacent rows. Working cycle times, productivity and costs were determined through a time-motion study of the forwarder. The additional variables evaluated were wood assortments (industrial wood and energy wood) and extraction distances (50, 100, 150 and 200 m), and mean values were compared between thinning methods using t tests for independent samples (α=0.05). Loading and unloading elements consumed the most time in the working cycle, with lower participation time in TH7 due to greater availability of logs along the strip roads (higher pile volumes), influencing total cycle time up to the mean distance of 150 m for both assortments. TH7 consequently showed 6% higher productivity, its energy yield was 5.3% lower and its production cost was 3.0% lower.
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Goicoechea, P. G., A. Roca, A. R. Linde, T. Naranjo, and R. Giraldez. "Independent arrangement of bivalents and (or) quadrivalents in linear meiotic metaphase plates of rye." Genome 34, no. 3 (June 1, 1991): 421–29. http://dx.doi.org/10.1139/g91-064.
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The relative positioning of bivalents and (or) quadrivalents in flattened lateral views of metaphase I (linear metaphase plates) has been analyzed in three different plant types of rye: normal plants (type 1); heterozygotes for translocation T305W (type 2); and double heterozygotes for translocations T305W and TR01 (type 3). In all plant types all bivalents and (or) quadrivalents were identified using C-banding. The results indicate that quadrivalents show a preference towards being located in marginal positions of the linear plate, and there are also differences in position preferences between specific bivalents. Adjacently oriented quadrivalents and rod bivalents show a stronger preference for marginal positions than alternate quadrivalents and ring bivalents, respectively, but this does not indicate the existence of a fixed or ordered arrangement of chromosomes in the spindle since bivalents and (or) quadrivalents are independently located relative to each other.Key words: Secale, meiosis, metaphase, arrangement, multivalents, bivalents.
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Kocić, Gordana, Jovan Hadzi-Djokić, Andrej Veljković, Stefanos Roumeliotis, Ljubinka Janković-Veličković, and Andrija Šmelcerović. "Template-Independent Poly(A)-Tail Decay and RNASEL as Potential Cellular Biomarkers for Prostate Cancer Development." Cancers 14, no. 9 (April 29, 2022): 2239. http://dx.doi.org/10.3390/cancers14092239.
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The post-transcriptional messenger RNA (mRNA) decay and turnover rate of the template-independent poly(A) tail, localized at the 3′-untranslated region (3′UTR) of mRNA, have been documented among subtle mechanisms of uncontrolled cancer tissue growth. The activity of Poly(A) deadenylase and the expression pattern of RNASEL have been examined. A total of 138 prostate tissue specimens from 46 PC patients (cancer specimens, corresponding adjacent surgically healthy tissues, and in their normal counterparts, at least 2 cm from carcinoma) were used. For the stratification prediction of healthy tissue transition into malignant phenotype, the enzyme activity of tumor-adjacent tissue was considered in relation to the presence of microfocal carcinoma. More than a four-times increase in specific enzyme activity (U/L g.prot) was registered in PC on account of both the dissociation of its inhibitor and genome reprogramming. The obtained ROC curve and Youden index showed that Poly(A) deadenylase identified PC with a sensitivity of 93.5% and a specificity of 94.6%. The RNASEL expression profile was raised significantly in PC, but the sensitivity was 40.5% and specificity was 86.9%. A significantly negative correlation between PC and control tissue counterparts with a higher expression pattern in lymphocyte-infiltrated samples were reported. In conclusion, significantly upregulated Poly(A) deadenylase activity may be a checkpoint for the transition of precancerous lesion to malignancy, while RNASEL may predict chronic inflammation.
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Yan, Ning, Cong Liu, Fang Tian, Ling Wang, Yimin Wang, Zhaoying Yang, Yan Jiao, and Miao He. "Downregulated mRNA Expression of ZNF385B Is an Independent Predictor of Breast Cancer." International Journal of Genomics 2021 (February 3, 2021): 1–13. http://dx.doi.org/10.1155/2021/4301802.
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Background. ZNF385B, a zinc finger protein, has been known as a potential biomarker in some neurological and hematological studies recently. Although numerous studies have demonstrated the potential function of zinc finger proteins in tumor progression, the effects of ZNF385B in breast cancer (BC) are less studied. Methods. The Oncomine database and “ESurv” tool were used to explore the differential expression of ZNF385B in pan-cancer. Furthermore, data of patients with BC were downloaded from The Cancer Genome Atlas (TCGA). The receiver operating characteristic (ROC) curve of ZNF385B expression was established to explore the diagnostic value of ZNF385B and to obtain the cut-off value of high or low ZNF385B expression in BC. The chi-square test as well as Fisher exact test was used for identification of the relationships between clinical features and ZNF385B expression. Furthermore, the effects of ZNF385B on BC patients’ survival were evaluated by the Kaplan-Meier and Cox regression. Data from the Gene Expression Omnibus (GEO) database were employed to validate the results of TCGA. Protein expression of ZNF385B in BC patient specimens was detected by immunohistochemistry (IHC) staining. Results. ZNF385B expression was downregulated in most types of cancer including BC. Low ZNF385B expression was related with survival status, overall survival (OS), and recurrence of BC. ZNF385B had modest diagnostic value, which is indicated by the area under the ROC curve ( AUC = 0.671 ). Patients with lower ZNF385B expression had shorter OS and RFS (relapse-free survival). It had been demonstrated that low ZNF385B expression represented independent prognostic value for OS and RFS by multivariate survival analysis. The similar results were verified by datasets from the GEO database as well. The protein expression of ZNF385B was decreased in patients’ samples compared with adjacent tissues by IHC. Conclusions. Low ZNF385B expression was an independent predictor for worse prognosis of BC patients.
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Humphreys, Tom, and Philip S. Marcus. "Vortex Street Dynamics: The Selection Mechanism for the Areas and Locations of Jupiter’s Vortices." Journal of the Atmospheric Sciences 64, no. 4 (April 1, 2007): 1318–33. http://dx.doi.org/10.1175/jas3882.1.
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Abstract With the exception of the Great Red Spot, Jupiter’s long-lived vortices are not isolated, but occur in east–west rows. Each row is centered about a westward-going jet stream with anticyclones on the poleward side and cyclones on the equatorial. Vortices are staggered so that like-signed vortices are never longitudinally adjacent. These double rows of vortices, called here Jovian vortex streets (JVSs) are robust. Calculations with no forcing and no dissipation (i.e., Hamiltonian dynamics) allow a continuum of JVS solutions, so they cannot be used to determine the physics that selects the observed values of the areas, circulations, and locations of Jupiter’s vortices. Constraints imposed by stability put few bounds on these values. When small amounts of dissipation and forcing are added to the governing equations, there is no longer a continuum of solutions; an initial JVS that was a solution of the Hamiltonian equations is now out of equilibrium and evolves to an attractor. For fixed forcing, all initial JVS evolve to the same attractor, so that the area of the vortices in the late-time JVS is selected uniquely as is the separation width in latitude between the row of cyclones and row of anticyclones. The separation width of the attracting JVS is nearly independent of the forcing, but the areas of the vortices in the attracting JVS depend strongly on the strength of the forcing, which is a measure of the ambient Jovian turbulence. Results are compared with observations.
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Jordan, Nicholas. "A Statistical Analysis for Area-of-Influence Experiments." Weed Technology 3, no. 1 (March 1989): 114–21. http://dx.doi.org/10.1017/s0890037x00031444.
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Area-of-influence (AOI3) experiments measure the effect of a single weed on crop growth at intervals away from the weed plant. Effects of treatment variables, e.g., weed species or control measures, on the AOI of a single weed can be estimated. AOI experiments can be analyzed by regression of crop growth on distance from the weed plant, but this analysis violates an important regression assumption: independece of observations. Statistical dependence can occur among successive observations along the row because uncontrolled sources of variation are likely to act in similar ways on adjacent individuals. Multivariate analysis of variance (MANOVA) is a statistical technique that accounts for dependencies among crop growth measurements along the row. The technique tests three hypotheses: first, that different treatments cause weed AOI to differ in spatial distribution of competitive effects; second, that different treatments cause weed AOI to differ in size; and third, that the weed has an effect, i.e., crop growth near the weed differs from growth away from weed. MANOVA can be applied to most common experimental designs, e.g., randomized blocks or split plots, and can be implemented on various mainframe and microcomputer statistical packages.
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Persi, Erez, Davide Prandi, Yuri I. Wolf, Yair Pozniak, Georgina D. Barnabas, Keren Levanon, Iris Barshack, et al. "Proteomic and genomic signatures of repeat instability in cancer and adjacent normal tissues." Proceedings of the National Academy of Sciences 116, no. 34 (August 6, 2019): 16987–96. http://dx.doi.org/10.1073/pnas.1908790116.
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Repetitive sequences are hotspots of evolution at multiple levels. However, due to difficulties involved in their assembly and analysis, the role of repeats in tumor evolution is poorly understood. We developed a rigorous motif-based methodology to quantify variations in the repeat content, beyond microsatellites, in proteomes and genomes directly from proteomic and genomic raw data. This method was applied to a wide range of tumors and normal tissues. We identify high similarity between repeat instability patterns in tumors and their patient-matched adjacent normal tissues. Nonetheless, tumor-specific signatures both in protein expression and in the genome strongly correlate with cancer progression and robustly predict the tumorigenic state. In a patient, the hierarchy of genomic repeat instability signatures accurately reconstructs tumor evolution, with primary tumors differentiated from metastases. We observe an inverse relationship between repeat instability and point mutation load within and across patients independent of other somatic aberrations. Thus, repeat instability is a distinct, transient, and compensatory adaptive mechanism in tumor evolution and a potential signal for early detection.
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Iwama, Atsuko, Shintaro Yamazaki, Yusuke Mitsuka, Nao Yoshida, Masamichi Moriguchi, Tokio Higaki, and Tadatoshi Takayama. "A Longitudinal Computed Tomography Imaging in the Diagnosis of Gallbladder Cancer." Gastroenterology Research and Practice 2015 (2015): 1–7. http://dx.doi.org/10.1155/2015/254156.
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Background/Aim. To assess whether the diagnostic power of longitudinal multiplanar reformat (MPR) images is superior to that of conventional horizontal images for gallbladder cancer (GBC).Methods.Between 2006 and 2010, a total of 54 consecutive patients with preoperatively diagnosed gallbladder neoplasms located in gallbladder bed were analyzed. These patients underwent cholecystectomy with resection of the adjacent liver parenchyma. The patients were divided into the GBC group (n=30) and the benign group (n=24). MPR images obtained by preoperative multidetector row CT (MDCT) were assessed.Results.Mucosal line was more significantly disrupted in GBC group than that in benign group (93% [28/30 patients] versus 13% [3/24],p<0.001). Maximum (9.3 [4.2–24.8] versus 7.0 mm [2.4–22.6],p=0.29) and minimum (1.2 [1.0–2.4] versus 1.3 mm [1.0–2.6],p=0.23) wall thicknesses on a single MPR plane did not differ significantly; however, the wall thickness ratio (max/min) differed significantly (6.8 [1.92–14.0] versus 5.83 [2.3–8.69],p=0.04). Partial liver enhancement adjacent to tumor on longitudinal images was more common in GBC (40.0% [12/30 patients] versus 12.5% [3/24],p=0.03). Mucosal line disruption was the most reliable independent predictor of diagnosis (odds ratio, 8.5; 95% CI, 5.99–28.1,p<0.001).Conclusion.Longitudinal MPR images are more useful than horizontal images for the diagnosis of GBC.
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Gupta, Sachin, Murat Sakir Eksi, Christopher P. Ames, Vedat Deviren, Blythe Durbin-Johnson, Justin S. Smith, and Munish C. Gupta. "A Novel 4-Rod Technique Offers Potential to Reduce Rod Breakage and Pseudarthrosis in Pedicle Subtraction Osteotomies for Adult Spinal Deformity Correction." Operative Neurosurgery 14, no. 4 (July 7, 2017): 449–56. http://dx.doi.org/10.1093/ons/opx151.
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Abstract BACKGROUND Pedicle subtraction osteotomy (PSO) can be used to treat rigid sagittal plane deformities. Nonunions and rod breakages are known complications of PSO. OBJECTIVE To assess outcomes of 2 methods of posterior instrumentation for PSO, traditional 2 rods vs a novel 4-rod technique in which 2 additional rods span only the osteotomy level. METHODS This study was a retrospective, radiographic review of consecutive PSOs performed at 2 centers. The primary difference in technique between the centers was the use of 4 rods including 2 independent rods attached only to the vertebral levels immediately adjacent to the PSO (group 1, n = 29 patients) vs the traditional 2-rod technique (group 2, n = 20 patients). RESULTS Demographics and preoperative to postoperative radiographic measurements were similar between the study groups, including the PSO wedge resection angle (P = .56). The rod breakage rate was 25% with 2 rods and 0% with 4 rods (P = .008), and the pseudarthrosis rate with 2 rods was 25% and with 4 rods was 3.4% (P = .035). The patient with pseudarthrosis from group 1 had an infection and developed pseudarthrosis only after instrumentation removal. Rates of other complications did not differ significantly between the study groups. CONCLUSION This study provides a comparison between 2 techniques for rod placement across a PSO and suggests that the described novel 4-rod technique may help to reduce the rates of pseudarthrosis and rod failure. It will be important to confirm these findings in a prospectively designed study with multiple institutions in order to better control for potentially confounding factors.
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Haldeman, Charles W., Michael Dunn, John W. Barter, Brian R. Green, and Robert F. Bergholz. "Experimental Investigation of Vane Clocking in a One and One-Half Stage High Pressure Turbine." Journal of Turbomachinery 127, no. 3 (March 1, 2004): 512–21. http://dx.doi.org/10.1115/1.1861915.
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Aerodynamic measurements were acquired on a modern single-stage, transonic, high-pressure turbine with the adjacent low-pressure turbine vane row (a typical civilian one and one-half stage turbine rig) to observe the effects of low-pressure turbine vane clocking on overall turbine performance. The turbine rig (loosely referred to in this paper as the stage) was operated at design corrected conditions using the Ohio State University Gas Turbine Laboratory Turbine Test Facility. The research program utilized uncooled hardware in which all three airfoils were heavily instrumented at multiple spans to develop a full clocking dataset. The low-pressure turbine vane row (LPTV) was clocked relative to the high-pressure turbine vane row (HPTV). Various methods were used to evaluate the influence of clocking on the aeroperformance (efficiency) and the aerodynamics (pressure loading) of the LPTV, including time-resolved and time-averaged measurements. A change in overall efficiency of approximately 2–3% due to clocking effects is demonstrated and could be observed using a variety of independent methods. Maximum efficiency is obtained when the time-average surface pressures are highest on the LPTV and the time-resolved surface pressure (both in the time domain and frequency domain) show the least amount of variation. The overall effect is obtained by integrating over the entire airfoil, as the three-dimensional (3D) effects on the LPTV surface are significant. This experimental data set validates several computational research efforts that suggested wake migration is the primary reason for the perceived effectiveness of vane clocking. The suggestion that wake migration is the dominate mechanism in generating the clocking effect is also consistent with anecdotal evidence that fully cooled engine rigs do not see a great deal of clocking effect. This is consistent since the additional disturbances induced by the cooling flows and∕or the combustor make it extremely difficult to find an alignment for the LPTV given the strong 3D nature of modern high-pressure turbine flows.
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Gérard, Anne-Catherine, Sylvie Poncin, Jean-Nicolas Audinot, Jean-François Denef, and Ides M. Colin. "Iodide deficiency-induced angiogenic stimulus in the thyroid occurs via HIF- and ROS-dependent VEGF-A secretion from thyrocytes." American Journal of Physiology-Endocrinology and Metabolism 296, no. 6 (June 2009): E1414—E1422. http://dx.doi.org/10.1152/ajpendo.90876.2008.
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Vascular supply is an obvious requirement for all organs. In addition to oxygen and nutrients, blood flow also transports essential trace elements. Iodine, which is a key element in thyroid hormone synthesis, is one of them. An inverse relationship exists between the expansion of the thyroid microvasculature and the local availability of iodine. This microvascular trace element-dependent regulation is unique and contributes to keep steady the iodide delivery to the thyroid. Signals involved in this regulation, such as VEGF-A, originate from thyrocytes as early TSH-independent responses to iodide scarcity. The question raised in this paper is how thyrocytes, facing an acute drop in intracellular stores of iodine, generate angiogenic signals acting on adjacent capillaries. Using in vitro models of rat and human thyroid cells, we show for the first time that the deficit in iodine is related to the release of VEGF-A via a reactive oxygen species/hypoxia-inducible factor-1-dependent pathway.
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WU, CHUI-JIE, LIANG WANG, and JIE-ZHI WU. "Suppression of the von Kármán vortex street behind a circular cylinder by a travelling wave generated by a flexible surface." Journal of Fluid Mechanics 574 (February 15, 2007): 365–91. http://dx.doi.org/10.1017/s0022112006004150.
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An advanced moving-wall control strategy to manage the unsteady separated flow over a circular cylinder is developed. A two-dimensional numerical simulation of the flow over the cylinder at Re=500 based on diameter indicates that, when the downstream half of the cylinder surface is made flexible to form an appropriate travelling transverse wave, a ‘fluid roller bearing’ (FRB) is produced consisting of a row of vortices trapped by each wave trough, which can keep the global flow attached against a strong adverse pressure gradient, eliminating the vortex shedding and reducing the average drag by 85%. Physically, the FRB serves as a sheath to effectively inhibit the momentum–energy exchange between the thin fluid layer adjacent to the wall and the main stream, so that the wall layer is scaled only to the local wavelength and frequency and is independent of the global scales. Therefore, the global adverse pressure gradient on the lee side of the cylinder no longer influences the near-wall flow, and the common root cause of flow separation is removed. The input power for actuating the flexible wall is found to be 94% of the power saving due to drag reduction.
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Chen, Aifeng, Shibiao Ding, Xiaoqiang Shen, and Xuai Lin. "The High Expression of PTPRH Is Associated with Poor Prognosis of Human Lung Adenocarcinoma." Computational and Mathematical Methods in Medicine 2021 (July 29, 2021): 1–9. http://dx.doi.org/10.1155/2021/9932088.
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Objective. The aim of the study is to explore the prognosis value of PTPRH in patients with lung adenocarcinoma (LUAD). Methods. Oncomine, UALCAN, and GEPIA databases were employed to examine the differential expression of PTPRH between LUAD and adjacent tissues. 100 pairs of LUAD and adjacent tissue samples were involved in this study. qRT-PCR and immunohistochemical staining were performed. Meanwhile, we analyzed The Cancer Genome Atlas (TCGA) data to investigate the correlation between PTPRH gene expression and clinicopathological characteristics. Kaplan-Meier analysis and univariate and multivariate Cox analyses were performed to estimate the relationship between PTPRH expression and LUAD prognosis. The evaluation performance was verified by drawing a ROC curve. In addition, through GSEA, the changes of PTPRH expression were analyzed by GSEA to screen out primarily affected signaling pathway. Results. Oncomine, UALCAN, and GEPIA databases showed that the mRNA expression of PTPRH in LUAD tissues was significantly higher than that in adjacent tissues. qRT-PCR and immunohistochemical staining indicated the mRNA and protein levels of PTPRH in LUAD tissues were markedly upregulated. TCGA data showed that the expression of PTPRH was significantly correlated with T stage and disease stage. Kaplan-Meier analysis showed that the patients with high PTPRH expression had a poor prognosis. Univariate and multivariate Cox analyses exhibited that PTPRH expression could act as an independent prognostic factor for LUAD. The ROC curve showed that PTPRH combined with various clinicopathological features could effectively predict the prognosis of LUAD. Finally, GSEA indicated that changes in PTPRH expression level may affect p53, VEGF, Notch, and mTOR cancer-related signaling pathways. Conclusion. Our results demonstrated that PTPRH was highly expressed in LUAD and may be closely correlated with the poor prognosis of LUAD patients.
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Lee, Seungbok, and Peter A. Kolodziej. "Short Stop provides an essential link between F-actin and microtubules during axon extension." Development 129, no. 5 (March 1, 2002): 1195–204. http://dx.doi.org/10.1242/dev.129.5.1195.
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Coordination of F-actin and microtubule dynamics is important for cellular motility and morphogenesis, but little is known about underlying mechanisms. short stop (shot) encodes an evolutionarily conserved, neuronally expressed family of rod-like proteins required for sensory and motor axon extension in Drosophila melanogaster. We identify Shot isoforms that contain N-terminal F-actin and C-terminal microtubule-binding domains, and that crosslink F-actin and microtubules in cultured cells. The F-actin- and microtubule-binding domains of Shot are required in the same molecule for axon extension, though the length of the connecting rod domain can be dramatically reduced without affecting activity. Shot therefore functions as a cytoskeletal crosslinker in axon extension, rather than mediating independent interactions with F-actin and microtubules. A Ca2+-binding motif located adjacent to the microtubule-binding domain is also required for axon extension, suggesting that intracellular Ca2+ release may regulate Shot activity. These results suggest that Shot coordinates regulated interactions between F-actin and microtubules that are crucial for neuronal morphogenesis.
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Baldauf, S., M. Scheurlen, A. Schulz, and S. Wittig. "Correlation of Film-Cooling Effectiveness From Thermographic Measurements at Enginelike Conditions." Journal of Turbomachinery 124, no. 4 (October 1, 2002): 686–98. http://dx.doi.org/10.1115/1.1504443.
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Adiabatic film-cooling effectiveness on a flat plate surface downstream of a row of cylindrical holes is investigated. Highly resolved two-dimensional surface data were measured by means of infrared thermography and carefully corrected for local conduction and radiation effects. These locally acquired data are laterally averaged to give the streamwise distributions of the effectiveness. An independent variation of the flow parameters blowing rate, density ratio, and turbulence intensity as well as the geometrical parameters streamwise ejection angle and hole spacing is examined. The influences of these parameters on the lateral effectiveness is discussed and interpreted with the help of surface distributions of effectiveness and heat transfer coefficients presented in earlier publications. Besides the known jet in cross-flow behavior of coolant ejected from discrete holes, these data demonstrate the effect of adjacent jet interaction and its impact on jet lift-off and adiabatic effectiveness. In utilizing this large matrix of measurements the effect of single parameters and their interactions are correlated. The important scaling parameters of the effectiveness are shaped out during the correlation process and are discussed. The resulting new correlation is designed to yield the quantitatively correct effectiveness as a result of the interplay of the jet in crossflow behavior and the adjacent jet interaction. It is built modularly to allow for future inclusion of additional parameters. The new correlation is valid without any exception within the full region of interest, reaching from the point of the ejection to far downstream, for all combinations of flow and geometry parameters.
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Merchant, M. E., and G. L. Teetes. "Suppression of Sorghum Midge, 1988." Insecticide and Acaricide Tests 14, no. 1 (January 1, 1989): 269. http://dx.doi.org/10.1093/iat/14.1.269.
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Abstract Two organophosphate and 2 pyrethroid insecticides were evaluated for sorghum midge control at the Texas Agricultural Experiment Station Research Farm near College Station. Grain sorghum was planted 5 May on rows spaced 40 inches apart. Sixteen rows of mixed hybrid sorghum of varying maturity ranges were planted 2 wk before adjacent to the test plots to increase sorghum midge abundance within the test plots during the flowering period. Treatments were compared in 8-row by 75-ft-long plots arranged in a randomized complete block design with 4 replicates. Applications were made with a self-propelled, high-clearance sprayer to all rows using TX-6 hollow-cone nozzles at 40 psi with a spray volume of 8 gal/acre. Insecticide applications were begun when 20-25% of the panicles were flowering. Treatments were applied 2, 6, and 10 Jul. Because of a rainfall that occurred 10 Jul during the spray operations the last application of Dyfonate was made 11 Jul. Karate plots received only 2 applications, on 2 and 6 Jul. Rainfall of 0.90, 0.45, and 1.33 inches occurred 4, 10, and 12 Jul, respectively, and may have influenced the outcome of the study. Data on ovipositing adult midge density, kernel damage, and grain yield were collected from the middle 6 rows of each plot. Adult sorghum midge abundance was determined just prior to each application and consisted of enclosing 10 individual sorghum panicles/plot with clear plastic bags. Panicles were subseqeuntly excised and returned to the laboratory for examination and counting of adult midges. Visual estimates of the percentage of midge damage were made by 4 independent observers on 8 Aug, with each observer estimating the percentage damage to 5 panicles/plot. Panicles were hand-harvested from 2 randomly selected 13-ft sections of row/plot and mechanically threshed.
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Wu, Wenjuan, Jing Sui, Tong Liu, Sheng Yang, Siyi Xu, Man Zhang, Shaoping Huang, Lihong Yin, Yuepu Pu, and Geyu Liang. "Integrated analysis of two-lncRNA signature as a potential prognostic biomarker in cervical cancer: a study based on public database." PeerJ 7 (April 22, 2019): e6761. http://dx.doi.org/10.7717/peerj.6761.
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Background Cervical cancer (CC) is a common gynecological malignancy in women worldwide. Evidence suggests that long non-coding RNAs (lncRNAs) can be used as biomarkers in patients with CC. However, prognostic biomarkers for CC are still lacking. The aim of our study was to find lncRNA biomarkers which are able to predict prognosis in CC based on the data from The Cancer Genome Atlas (TCGA). Methods The patients were divided into three groups according to FIGO stage. Differentially expressed lncRNAs were identified in CC tissue compared to adjacent normal tissues based on a fold change >2 and <0.5 at P < 0.05 for up- and downregulated lncRNA, respectively. The relationship between survival outcome and lncRNA expression was assessed with univariate and multivariate Cox proportional hazards regression analysis. We constructed a risk score as a method to evaluate prognosis. We used receiver operating characteristic (ROC) curve and the area under curve (AUC) analyses to assess the diagnostic value of a two-lncRNA signature. We detected the expression levels of the two lncRNAs in 31 pairs of newly diagnosed CC specimens and paired adjacent non-cancerous tissue specimens, and also in CC cell lines. Finally, the results were statistically compared using t-tests. Results In total, 289 RNA sequencing profiles and accompanying clinical data were obtained. We identified 49 differentially expressed lncRNAs, of which two related to overall survival (OS) in CC patients. These two lncRNAs (ILF3-AS1 and RASA4CP) were found together as a single prognostic signature. Meanwhile, the prognosis of patients with low-risk CC was better and positively correlated with OS (P < 0.001). Further analysis showed that the combined two-lncRNA expression signature could be used as an independent biomarker to evaluate the prognosis in CC. qRT-PCR results were consistent with TCGA, confirming downregulated expression of both lncRNAs. Furthermore, upon ROC curve analysis, the AUC of the combined lncRNAs was greater than that of the single lncRNAs alone (0.723 vs 0.704 and 0.685), respectively; P < 0.05. Conclusions Our study showed that the two-lncRNA signature of ILF3-AS1 and RASA4CP can be used as an independent biomarker for the prognosis of CC, based on bioinformatic analysis.
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Chen, Jie, Jing-Yun Wen, Zhan-Hong Chen, Qu Lin, Xiao-Kun Ma, Li Wei, Xing Li, et al. "Use of the mitotic kinase aurora-A activation to predict outcome for primary duodenal adenocarcinoma." Journal of Clinical Oncology 31, no. 15_suppl (May 20, 2013): 4131. http://dx.doi.org/10.1200/jco.2013.31.15_suppl.4131.
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4131 Background: We and others had proved that hypoxia-inducible factor-1α (HIF-1α) and transcriptionally upregulated Aurora-A were required for disease progression in several tumors. Methods: We addressed the clinicopathologic value of HIF-1α and Aurora-a in primary duodenal adenocarcinoma (PDA). Aurora-a and HIF-1α expression were semi-quantitative evaluated by immunohistochemistry in 140 PDA. Among which, 76 patients from one institute acted as training set, and 64 cases from another two institutes were used as testing set to validate the prognostic effect of Aurora-a and HIF-1α. Results: We found that Aurora-a was high or sufficient expressed in tumor zone, whereas low-expressed in the normal adjacent epithelia. Moreover, Aurora-a high expression, classified by training set ROC analysis-generated cutoff score, predicted an inferior overall survival both in testing set and training set. Multivariate Cox regression confirmed that Aurora-a was indeed an independent prognostic factor (Table). Contrary to previous studies, we did not detect any correlation between Aurora-a and HIF-1α in PDA. Additionally, survival analysis showed that HIF-1α level was not correlated with patient outcome (p = 0.466). Conclusions: Activation of Aurora-A, an independent negative prognostic biomarker, might be used to identify particular patients for more selective therapy. [Table: see text]
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Pewarchuk, Michelle E., Mateus C. Barros-Filho, Brenda C. Minatel, David E. Cohn, Florian Guisier, Adam P. Sage, Erin A. Marshall, et al. "Upgrading the Repertoire of miRNAs in Gastric Adenocarcinoma to Provide a New Resource for Biomarker Discovery." International Journal of Molecular Sciences 20, no. 22 (November 14, 2019): 5697. http://dx.doi.org/10.3390/ijms20225697.
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Recent studies have uncovered microRNAs (miRNAs) that have been overlooked in early genomic explorations, which show remarkable tissue- and context-specific expression. Here, we aim to identify and characterize previously unannotated miRNAs expressed in gastric adenocarcinoma (GA). Raw small RNA-sequencing data were analyzed using the miRMaster platform to predict and quantify previously unannotated miRNAs. A discovery cohort of 475 gastric samples (434 GA and 41 adjacent nonmalignant samples), collected by The Cancer Genome Atlas (TCGA), were evaluated. Candidate miRNAs were similarly assessed in an independent cohort of 25 gastric samples. We discovered 170 previously unannotated miRNA candidates expressed in gastric tissues. The expression of these novel miRNAs was highly specific to the gastric samples, 143 of which were significantly deregulated between tumor and nonmalignant contexts (p-adjusted < 0.05; fold change > 1.5). Multivariate survival analyses showed that the combined expression of one previously annotated miRNA and two novel miRNA candidates was significantly predictive of patient outcome. Further, the expression of these three miRNAs was able to stratify patients into three distinct prognostic groups (p = 0.00003). These novel miRNAs were also present in the independent cohort (43 sequences detected in both cohorts). Our findings uncover novel miRNA transcripts in gastric tissues that may have implications in the biology and management of gastric adenocarcinoma.
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Zhang, Wen, Zhengquan Cai, Mingzhu Kong, Anqi Wu, Zeyang Hu, Feng Wang, and Hua Wang. "Prognostic significance of TRIM28 expression in patients with breast carcinoma." Open Medicine 16, no. 1 (January 1, 2021): 472–80. http://dx.doi.org/10.1515/med-2021-0263.
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Abstract Background Tripartite motif 28 (TRIM28) plays a role in multiple biological functions. The expression and function of TRIM28 in breast carcinoma (BC) remain unclear. The aim of this study was to explore potential association of TRIM28 with tumor features and survival. Materials and methods Specimens were collected from BC and adjacent normal tissues. Quantitative reverse transcription PCR (RT-qPCR) and immunohistochemistry (IHC) were performed to detect TRIM28 expression. The correlation of TRIM28 with clinicopathological features was evaluated by Chi-square test. The relationship between TRIM28 expression and survival was further analyzed by the Kaplan-Meier and Cox regression method. A receiver operating characteristic (ROC) curve was used to assess the value of TRIM28 in predicting BC. Results In this retrospective research, it was demonstrated that TRIM28 was overexpressed in BC tissues. TRIM28 overexpression was correlated with lymph node metastasis, advanced TNM stage, and poor molecular subtype. The survival analysis showed that overall survival (OS) and progression-free survival (PFS) were significantly shorter in TRIM28-positive group. Moreover, TRIM28 was an independent prognostic factor for BC. And ROC analysis verified the diagnostic role of TRIM28 in BC. Conclusions TRIM28 is overexpressed in BC and might be a promising prognostic and diagnostic biomarker of BC.
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Ma, Weijie, Zhenfei Hong, Hailing Liu, Xi Chen, Lu Ding, Zhisu Liu, Fuling Zhou, and Yufeng Yuan. "Human Endogenous Retroviruses-K (HML-2) Expression Is Correlated with Prognosis and Progress of Hepatocellular Carcinoma." BioMed Research International 2016 (2016): 1–9. http://dx.doi.org/10.1155/2016/8201642.
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Background. The association between human endogenous retroviruses-K (HERV-K) (HML-2) and human disease, including a variety of cancers, has been indicated. However, the function of HERV-K (HML-2) in the progression of hepatocellular carcinoma (HCC) still remains largely unclear.Methods. We detected the expression of HERV-K (HML-2) in 84 HCC tissues and adjacent nontumor tissues by quantitative real-time PCR (qRT-PCR) and analyzed its correlation with the clinical parameters.Result. The HEVR-K level was significantly increased in HCC compared with adjacent normal tissues (P<0.01) which was proved to be significantly associated with cirrhosis (P<0.05), tumor differentiation (P<0.05), and TNM stage (P<0.05). Moreover, the high expression of HERV-K (HML-2) had a poorer overall survival than patients with lower expression by a Kaplan-Meier survival analysis (P<0.01). The multivariate Cox regression analysis indicated that the level of HERV-K (HML-2) was an independent prognostic factor for the overall survival rate of HCC patients. Receiver operating characteristic (ROC) curves demonstrated the diagnostic accuracy of HERV-K (HML-2) expression in HCC (AUC = 0.729, 74.7% sensitivity, and 67.8% specificity).Conclusions. Our results suggested that upregulation of HERV-K (HML-2) in HCC patients was significantly related to cancer progression and poor outcome, indicating that HERV-K (HML-2) might be a novel candidate prognostic biomarker for HCC.
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Zhang, Yinglang, Zhe Zhang, Wei Zhang, Hailong Hu, and Guochang Bao. "Upregulated Transcription Factor PITX1 Predicts Poor Prognosis in Kidney Renal Clear Cell Carcinoma-Based Bioinformatic Analysis and Experimental Verification." Disease Markers 2021 (November 23, 2021): 1–19. http://dx.doi.org/10.1155/2021/7694239.
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Paired-like homeodomain transcription factor 1 (PITX1) is involved in numerous biological processes, including cell growth, progression, and invasion in various malignant tumors. Nevertheless, the relationship between PITX1 and kidney renal clear cell carcinoma (KIRC) remains unclear. The clinical role and functions of PITX1 were analyzed by integrating multiple open-access online datasets. Further experimental verification was performed via quantitative real-time PCR (qRT-PCR) to detect the expression of PITX1 in 10 pairs of KIRC tissues. Our results revealed that PITX1 mRNA was overexpressed in tumor tissues compared with normal tissues in the TCGA-KIRC database ( p < 0.001 ) and numerous independent cohorts ( p < 0.05 ). Further, high expression of PITX1 mRNA was detected in KIRC tissues compared with adjacent normal tissues in our center by qRT-PCR ( N = 10 , p < 0.05 ). Logistic regression analysis demonstrated that the PITX1 level was positively associated with KIRC patients, T and M stages, histologic grade, and pathologic stage (all p < 0.05 ). Survival analysis showed that upregulation of PITX1 mRNA was associated with poor overall survival (OS), disease-free survival (DFS), and disease-specific survival (DSS) (all p < 0.05 ). Univariate/multivariate Cox hazard regression analysis revealed that PITX1 was an independent risk factor for OS in patients with KIRC ( HR = 1.998 , p = 0.003 ). Accordingly, the time-independent receiver operating characteristic (ROC) curve confirmed that PITX1 had good predictive efficacy for OS and DSS. Meanwhile, a prediction model constructed by nomogram was used to predict the OS of KIRC patients, and the calibration plot indicated this model shows high accuracy. We also revealed some downstream target genes of PITX1-related signaling pathways. Our finding suggested that high PITX1 mRNA expression may act as an independent predictive factor of poor prognosis in patients with KIRC. The prognostic model based on the nomogram would be instrumental in evaluating the survival rate in KIRC patients.
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Alam, SK, EJ Feleppa, Mark Rondeau, A. Kalisz, and BS Garra. "Computer-Aided Diagnosis of Solid Breast Lesions Using an Ultrasonic Multi-Feature Analysis Procedure." Bangladesh Journal of Medical Physics 4, no. 1 (April 19, 2013): 1–10. http://dx.doi.org/10.3329/bjmp.v4i1.14672.
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We have developed a family of quantitative descriptors in order to provide noninvasive, reliable means of distinguishing benign from malignant breast lesions. These include acoustic descriptors (echogenicity, heterogeneity, shadowing) and morphometric descriptors (area, aspect ratio, border irregularity, margin definition). These quantitative descriptors are designed to be independent of instrument properties and physician expertise. Our analysis included manual tracing of lesion boundaries and adjacent areas on grayscale images generated from RF data. To derive quantitative acoustic features, we computed spectral-parameter maps of radio-frequency (RF) echo signals (using a sliding-window Fourier analysis) of the lesion and adjacent areas. We quantified morphometric features by geometric and fractal analysis of traced lesion boundaries. Although no single parameter can reliably discriminate cancerous from non-cancerous breast lesions, multi-feature analysis provides excellent discrimination of cancerous and non-cancerous lesions. Our analysis of data acquired during routine ultrasonic examination of 130 biopsy-scheduled patients produced a receiver-operating characteristic (ROC) area under the curve (AUC) of 0.947±0.045. Lesion-margin definition, spiculation, and border irregularity were the most useful among the quantitative descriptors; some morphometric features (such as border irregularity) also were particularly effective in lesion classification. Our results are consistent with many of the Breast Imaging Reporting and Data System (BI-RADS) breast-lesion-classification criteria in use today. DOI: http://dx.doi.org/10.3329/bjmp.v4i1.14672 Bangladesh Journal of Medical Physics Vol.4 No.1 2011 1-10
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Mei, Jun-chi, Ge Yan, and Si-qing Mei. "Diagnostic and Prognostic Potentials of Long Noncoding RNA ELF3-AS1 in Glioma Patients." Disease Markers 2020 (September 18, 2020): 1–7. http://dx.doi.org/10.1155/2020/8871746.
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Objective. Accumulating evidence implies that long noncoding RNAs (lncRNAs) play a crucial role in predicting survival for glioma patients. However, the potential function of lncRNA ELF3-antisense RNA 1 (ELF3-AS1) in tumors remained largely unclear. The aim of this study was to explore the expression of lncRNA ELF3-antisense RNA 1 (ELF3-AS1) and evaluate its functions in glioma patients. Patients and Methods. ELF3-AS1 expressions were examined by RT-PCR in 182 pairs of glioma specimens and adjacent normal tissues. The receiver operating characteristic (ROC) curve was performed to estimate the diagnostic value of ELF3-AS1. The chi-square tests were used to examine the associations between ELF3-AS1 expression and the clinicopathological characters. The overall survival (OS) and disease-free survival (DFS) were analyzed by log-rank test, and survival curves were plotted according to Kaplan-Meier. The prognostic value of the ELF3-AS1 expression in glioma patients was further analyzed using univariate and multivariate Cox regression analyses. Loss-of-function assays were performed to determine the potential function of ELF3-AS1 on the proliferation and invasion of glioma cells. Results. The ELF3-AS1 expression level was significantly higher in glioma specimens compared with adjacent nontumor specimens (p<0.01). A high expression of ELF3-AS1 was shown to be associated with the WHO grade (p=0.023) and KPS score (p=0.012). ROC assays revealed that high ELF3-AS1 expression had an AUC value of 0.8073 (95% CI: 0.7610 to 0.8535) for glioma. Using the Kaplan-Meier analysis, we found that patients with a high ELF3-AS1 expression had significantly poor OS (p=0.006) and DFS (p=0.0002). In a multivariate Cox model, we confirmed that ELF3-AS1 expression was an independent poor prognostic factor for glioma patients. The functional assay revealed that knockdown of ELF3-AS1 suppressed the proliferation and invasion of glioma cells. Conclusions. Our findings confirmed that ELF3-AS1 functions as an oncogene in glioma and indicated that ELF3-AS1 is not only an important prognostic marker but also a potential therapy target for glioma.
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Robinson, John R. C., and George L. Teetes. "Insecticides for Suppression of Sorghum Midge on Dryland Grain Sorghum, 1987." Insecticide and Acaricide Tests 13, no. 1 (January 1, 1988): 277. http://dx.doi.org/10.1093/iat/13.1.277a.
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Abstract Grain sorghum (1.8 acres) was planted 19 May on rows spaced 40 inches apart. Twelve rows of mixed-hybrid sorghums of varying maturity ranges were planted prior to and adjacent to the test plot to increase abundance of sorghum midge during anthesis of sorghum panicles in the test plots. Five insecticide treatments and an untreated check were compared in a randomized block design with 4 replications. Experimental plots were 8 rows wide and 80 ft long. Applications were made to the middle 6 rows with a high-clearance self-propelled sprayer. Insecticide applications began when 30-40% of the panicles were flowering and when average adult midge density was 0.7 midges/panicle. Treatments were applied 24 and 30 Jul and 4 Aug. Adult midge density was determined 1 day prior to application of insecticide treatments. Sampling consisted of securing and collecting individual sorghum panicles in plastic bags. Samples were examined in the laboratory and midges were counted. Prior to the first insecticide application, midge density was determined from sampling 25 randomly selected panicles/replication. On the 2 subsequent sampling days, 5 panicles were sampled from each treatment plot. Visual estimates of the percentage of midge-damaged spikelets were made by 4 independent observers, with each observer rating 10 randomly selected panicles/plot. Panicles were hand harvested from 2, 2-m sections of treated row/plot. The harvested sorghum panicles were threshed, and the grain was weighed. Data were analyzed by conventional analysis of variance and multiple comparison procedures.
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Friese, Volker. "A cluster-finding algorithm for free-streaming data." EPJ Web of Conferences 214 (2019): 01008. http://dx.doi.org/10.1051/epjconf/201921401008.
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In position-sensitive detectors with segmented readout (pixels or strips), charged particles activate in general several adjacent read-out channels. The first step in the reconstruction of the hit position is thus to identify clusters of active channels associated to one particle crossing the detector. In conventionally triggered systems, where the association of raw data to events is given by a hardware trigger, this is an easy-to-solve problem. It, however, becomes more involved in untriggered, free-streaming read-out systems like the one employed by the CBM experiment. Here, the time coordinate of the single-channel measurement must be taken into account to decider whether neighbouring active channels belong to a cluster. A simple extension of well-known cluster finding algorithms is not satisfactory because of involving increasing combinatorics, which are prohibitive for reconstruction in real-time. In this article, a cluster-finding solution for the Silicon Tracking System of the CBM experiment is presented which avoids any combinatorics or loops over detector channels. Its execution time is thus independent on the size of the data packages (time slices) delivered by the data acquisition, making it suitable for being used in online reconstruction.
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Qiao, Siqi, Baochang Liu, and Yijun He. "Improved Analytical Formula for the SAR Doppler Centroid Estimation Standard Deviation for a Dynamic Sea Surface." Remote Sensing 15, no. 3 (February 3, 2023): 867. http://dx.doi.org/10.3390/rs15030867.
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The existing formulas for the synthetic aperture radar (SAR) Doppler centroid estimation standard deviation (STD) suffer from various limitations, especially for a dynamic sea surface. In this study, we derive an improved version of these formulas through three steps. First, by considering the ocean wavenumber spectrum information, a new strategy for determining the number of independent samples of the sea wave velocity field is adopted in the new formula. This is contrary to the method used in the existing formulas, where the number of SAR geometric resolution cells is taken as the number of samples assuming that adjacent SAR resolution cells are statistically uncorrelated. Second, the pulse repetition frequency and Doppler bandwidth are decoupled in the new formula, unlike in the existing formulas where they are unchangeably related to each other. Third, the effects of thermal noise and Doppler aliasing are jointly quantified in a mathematically exact manner instead of being treated separately, as in the existing formulas. Comprehensive SAR raw data simulations for the ocean surface show that the new formula has a better performance in predicting the Doppler centroid estimation STD than the existing formulas.
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Zhu, Yunyang, Zhaoming Song, Zhong Wang, and Gang Chen. "Protective Prognostic Biomarkers Negatively Correlated with Macrophage M2 Infiltration in Low-Grade Glioma." Journal of Oncology 2022 (April 8, 2022): 1–22. http://dx.doi.org/10.1155/2022/3623591.
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Tumor-associated Macrophages (TAMs) play a vital role in the progression of glioma. Macrophage M2 has been confirmed to promote immunosuppression and proliferation of low-grade glioma (LGG). Here, we searched for genes negatively correlated with Macrophages M2 by bioinformatical methods and investigated their protective ability for prognosis. LGG and adjacent normal samples were screened out in TCGA and three GEO datasets. 326 overlapped differentially expressed genes were calculated, and their biological functions were investigated by Go and KEGG analyses. Macrophage M2 accounted for the highest proportion among all 22 immune cells by CIBERSORT deconvolution algorithm. The proportion of Macrophage M2 in LGG was also higher than that in normal tissue according to several deconvolution algorithms. 43 genes in the blue module negatively correlated with Macrophage M2 infiltration were identified by weighted gene coexpression network analysis (WGCNA). Through immune infiltration and correlation analysis, FGFBP3, VAX2, and SHD were selected and they were enriched in G protein-coupled receptors’ signaling regulation and cytokine receptor interaction. They could prolong the overall and disease-free survival time. Univariate and multivariate Cox regression analyses were applied to evaluate prognosis prediction ability. Interestingly, FGFBP3 and AHD were independent prognostic predictors. A nomogram was drawn, and its 1-year, 3-year, and 5-year survival prognostic value was verified by ROC curves and calibration plots. In conclusion, FGFBP3, VAX2, and SHD were protective prognostic biomarkers against Macrophage M2 infiltration in low-grade glioma. The FGFBP3 and SHD were independent factors to effectively predict long-term survival probability.
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Chen, Qi-Yue, Qing Zhong, Jun-Feng Zhou, Xian-Tu Qiu, Xue-Yi Dang, Li-Sheng Cai, Guo-Qiang Su, et al. "Development and External Validation of Web-Based Models to Predict the Prognosis of Remnant Gastric Cancer after Surgery: A Multicenter Study." Journal of Oncology 2019 (April 10, 2019): 1–15. http://dx.doi.org/10.1155/2019/6012826.
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Background. Remnant gastric cancer (RGC) is a rare malignant tumor with poor prognosis. There is no universally accepted prognostic model for RGC. Methods. We analyzed data for 253 RGC patients who underwent radical gastrectomy from 6 centers. The prognosis prediction performances of the AJCC7th and AJCC8th TNM staging systems and the TRM staging system for RGC patients were evaluated. Web-based prediction models based on independent prognostic factors were developed to predict the survival of the RGC patients. External validation was performed using a cohort of 49 Chinese patients. Results. The predictive abilities of the AJCC8th and TRM staging systems were no better than those of the AJCC7th staging system (c-index: AJCC7th vs. AJCC8th vs. TRM, 0.743 vs. 0.732 vs. 0.744; P>0.05). Within each staging system, the survival of the two adjacent stages was not well discriminated (P>0.05). Multivariate analysis showed that age, tumor size, T stage, and N stage were independent prognostic factors. Based on the above variables, we developed 3 web-based prediction models, which were superior to the AJCC7th staging system in their discriminatory ability (c-index), predictive homogeneity (likelihood ratio chi-square), predictive accuracy (AIC, BIC), and model stability (time-dependent ROC curves). External validation showed predictable accuracies of 0.780, 0.822, and 0.700, respectively, in predicting overall survival, disease-specific survival, and disease-free survival. Conclusions. The AJCC TNM staging system and the TRM staging system did not enable good distinction among the RGC patients. We have developed and validated visual web-based prediction models that are superior to these staging systems.
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Veleba, Mark, Paul G. Higgins, Gerardo Gonzalez, Harald Seifert, and Thamarai Schneiders. "Characterization of RarA, a Novel AraC Family Multidrug Resistance Regulator in Klebsiella pneumoniae." Antimicrobial Agents and Chemotherapy 56, no. 8 (May 29, 2012): 4450–58. http://dx.doi.org/10.1128/aac.00456-12.
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ABSTRACTTranscriptional regulators, such as SoxS, RamA, MarA, and Rob, which upregulate the AcrAB efflux pump, have been shown to be associated with multidrug resistance in clinically relevant Gram-negative bacteria. In addition to the multidrug resistance phenotype, these regulators have also been shown to play a role in the cellular metabolism and possibly the virulence potential of microbial cells. As such, the increased expression of these proteins is likely to cause pleiotropic phenotypes.Klebsiella pneumoniaeis a major nosocomial pathogen which can express the SoxS, MarA, Rob, and RamA proteins, and the accompanying paper shows that the increased transcription oframAis associated with tigecycline resistance (M. Veleba and T. Schneiders, Antimicrob. Agents Chemother. 56:4466–4467, 2012). Bioinformatic analyses of the availableKlebsiellagenome sequences show that an additional AraC-type regulator is encoded chromosomally. In this work, we characterize this novel AraC-type regulator, hereby called RarA (Regulator of antibiotic resistance A), which is encoded inK. pneumoniae,Enterobactersp. 638,Serratia proteamaculans568, andEnterobacter cloacae. We show that the overexpression ofrarAresults in a multidrug resistance phenotype which requires a functional AcrAB efflux pump but is independent of the other AraC regulators. Quantitative real-time PCR experiments show thatrarA(MGH 78578 KPN_02968) and its neighboring efflux pump operonoqxAB(KPN_02969_02970) are consistently upregulated in clinical isolates collected from various geographical locations (Chile, Turkey, and Germany). Our results suggest thatrarAoverexpression upregulates theoqxABefflux pump. Additionally, it appears thatoqxR, encoding a GntR-type regulator adjacent to theoqxABoperon, is able to downregulate the expression of theoqxABefflux pump, where OqxR complementation resulted in reductions to olaquindox MICs.
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Kapetas, Panagiotis, Katja Pinker-Domenig, Ramona Woitek, Paola Clauser, Maria Bernathova, Claudio Spick, Thomas Helbich, and Pascal A. Baltzer. "Clinical application of Acoustic Radiation Force Impulse Imaging with Virtual Touch IQ in breast ultrasound: diagnostic performance and reproducibility of a new technique." Acta Radiologica 58, no. 2 (July 19, 2016): 140–47. http://dx.doi.org/10.1177/0284185116641347.
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Background Virtual Touch IQ (VTIQ) is a novel technique of quantitative sonoelastography that applies acoustic radiation force impulse (ARFI). Purpose To evaluate breast ARFI imaging with VTIQ in the clinical setting, with regard to reproducibility and diagnostic performance, and to specify cutoff limits for the differentiation of benign and malignant lesions. Material and Methods This retrospective study included 83 patients with 85 breast lesions (51 benign, 34 malignant) who received ARFI imaging with VTIQ. Two independent ARFI measurements of each lesion were performed and shear wave velocities (SWV) of the lesion and the adjacent tissues were measured. A lesion-to-fat velocity ratio (L/F Ratio) was calculated for each lesion. Diagnostic performance of SWV measurements and L/F Ratios was evaluated with receiver operating curve (ROC) analysis. The intraclass correlation coefficient and Bland–Altman plots were used to evaluate measurement reproducibility. Results All measurements showed equal diagnostic performance, as measured by the area under the ROC curve (0.853 for SWV, 0.882 for the L/F Ratio). At a cutoff value of 3.23 m/s, sensitivity and specificity were 82.4% and 80.4%, respectively. An L/F Ratio cutoff value of 2.23 revealed a sensitivity and specificity of 89.7% and 76.5%. The reproducibility of the SWV measurements was moderate (limits of agreement, 40.3–44.4%) and higher than that of the L/F Ratios (54.5–60.2%). Conclusion ARFI imaging with VTIQ is a novel, moderately reproducible, quantitative elastography technique, which provides useful information for the differentiation of benign and malignant breast lesions in the clinical setting.
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He, Tao, Xiangyu Guo, Xue Li, Chunjuan Liao, Xiaorong Wang, and Kun He. "Plasma-Derived Exosomal microRNA-130a Serves as a Noninvasive Biomarker for Diagnosis and Prognosis of Oral Squamous Cell Carcinoma." Journal of Oncology 2021 (April 16, 2021): 1–9. http://dx.doi.org/10.1155/2021/5547911.
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Exosomal microRNAs (miRNAs) are considered as potential stable biomarkers in many types of human cancer, but investigations of plasma-derived exosomal miRNAs in oral squamous cell carcinoma (OSCC) are still lacking. The aim of this study is to evaluate the diagnostic and prognostic values of exosomal miR-130a in OSCC patients. Exosomes were isolated from plasma samples which were collected from 184 OSCC patients before surgery and 196 healthy individuals. Primary OSCC and paired adjacent noncancerous tissues were also obtained from 47 OSCC patients. The expression levels of miR-130a were analyzed by quantitative real-time PCR (qRT-PCR). Our results showed that the expression levels of exosomal miR-130a were significantly higher in OSCC patients than those of the healthy controls ( p < 0.0001 ). Also, the expression of miR-130a was also significantly upregulated in OSCC tissues compared with paired adjacent noncancerous tissues ( p < 0.0001 ). A significant positive correlation was found between exosomal miR-130a and tissue miR-130a levels. Receiver operating characteristic (ROC) analyses yielded an AUC value of 0.812 in discriminating OSCC patients from healthy controls. Furthermore, high levels of exosomal miR-130a were associated with the late T-stage ( p = 0.024 ), advanced TNM stage ( p = 0.003 ), and poorly differentiated OSCC ( p = 0.013 ). Patients with high exosomal miR-130a expression had significantly worse 3-year overall survival (OS) and recurrence-free survival (RFS). Multivariate analysis indicated that exosomal miR-130a was an independent prognostic factor for OS ( p = 0.001 ) and RFS ( p = 0.003 ). Our results suggest that exosomal miR-130a may serve as a promising diagnostic and prognostic biomarker for OSCC patients.
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Robinson, John R. C., and George L. Teetes. "Chemical Control of Sorghum Midge on Grain Sorghum, 1986." Insecticide and Acaricide Tests 12, no. 1 (January 1, 1987): 270. http://dx.doi.org/10.1093/iat/12.1.270.
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Abstract 2.2 acres of grain sorghum were planted 15 May on rows spaced 40 inches apart. Twelve rows of mixed hybrid sorghums of varying maturity ranges were planted prior and adjacent to the test plot site to increase midge populations. Nine insecticide treatments and an untreated check were compared in a randomized block design with 4 replications. Experimental plots were 8 rows wide and 45 ft long, but only the middle 4 rows were sprayed. Applications were made with a high-clearance, self-propelled sprayer using TX-3 hollow cone nozzles and calibrated to deliver 5.9 GPA at 42 psi and 3 mph. Insecticide applications began when 30-40% of the panicles were flowering and when average adult midge density was 2.5 midges/panicle. Treatments were applied 11, 15 and 19 Jul. The first application was made under slightly adverse wind conditions (10-15 mph gusts). Adult midge density was determined 1 day prior to application of insecticide treatments. Sampling consisted of securing and collecting individual sorghum panicles in plastic bags. Samples were examined in the laboratory and midges were counted. Prior to the first insecticide application, midge density was determined from sampling 25 randomly selected panicles per replication. On the 2 subsequent sampling days, 5 panicles were sampled from each treatment plot. Visual estimates of percent midge damaged spikelets were made by 6 independent observers, with each observer rating 10 randomly selected panicles/plot. Panicles were hand harvested from one 20-ft section of treated row per plot. The harvested sorghum panicles were threshed and the grain was weighed. Data were analyzed by conventional analysis of variance and multiple comparison procedures.
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Barabé, Denis, Christian Lacroix, and Bernard Jeune. "The game of numbers in homeotic flowers of Philodendron (Araceae)." Canadian Journal of Botany 82, no. 10 (October 1, 2004): 1459–67. http://dx.doi.org/10.1139/b04-115.
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In Philodendron, pistillate flowers are initiated on the proximal portion of the inflorescence and staminate flowers are initiated on the distal portion. Between the staminate and pistillate flowers, there is a transition zone consisting of sterile male flowers adjacent to the male zone and a row of atypical bisexual flowers between the sterile male zone and the female zone. The portion of the atypical bisexual flower facing the male zone forms stamens, and the portion facing the female zone develops into an incomplete gynoecium with few carpels. The atypical bisexual flowers of Philodendron are believed to be a case of homeosis where carpels are replaced by sterile stamens on the same whorl. In Philodendron melinonii Brongniart ex Regel, Philodendron pedatum (Hooker) Kunth, Philodendron squamiferum Poeppig., and Philodendron solimoesense A.C. Smith, there is a significant quantitative relationship between the number of carpels and the number of staminodes involved in the homeotic transformation in atypical bisexual flowers. On the other hand, such a significant correlation does not exist in Philodendron fragrantissimum (Hooker) Kunth and Philodendron insigne Schott, and Philodendron callosum K. Krause. There is a one to one organ replacement in homeotic flowers in both P. pedatum and P. squamiferum whereas, in P. solimoesense, an average of 2.56 staminodes replace one carpel. The average number of organs developing on an atypical bisexual flower and the number of organs involved in a homeotic transformation appear to be two independent phenomena. The number of carpels in female flowers is correlated with the maximum total number of appendages (carpels and staminodes) that can develop in atypical bisexual flowers.Key words: development, inflorescence, gradient, position, information.
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Jiao, Yuming, Fuxin Lin, Jun Wu, Hao Li, Lijun Wang, Zhen Jin, Shuo Wang, and Yong Cao. "A supplementary grading scale combining lesion-to-eloquence distance for predicting surgical outcomes of patients with brain arteriovenous malformations." Journal of Neurosurgery 128, no. 2 (February 2018): 530–40. http://dx.doi.org/10.3171/2016.10.jns161415.
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OBJECTIVECase selection for the surgical treatment of brain arteriovenous malformations (BAVMs) remains challenging. This study aimed to construct a predictive grading system combining lesion-to-eloquence distance (LED) for selecting patients with BAVMs for surgery.METHODSBetween September 2012 and September 2015, the authors retrospectively studied 201 consecutive patients with BAVMs. All patients had undergone preoperative functional MRI and diffusion tensor imaging (DTI), followed by resection. Both angioarchitectural factors and LED were analyzed with respect to the change between preoperative and final postoperative modified Rankin Scale (mRS) scores. LED refers to the distance between the lesion and the nearest eloquent area (eloquent cortex or eloquent fiber tracts) measured on preoperative fMRI and DTI. Based on logistic regression analysis, the authors constructed 3 new grading systems. The HDVL grading system includes the independent predictors of mRS change (hemorrhagic presentation, diffuseness, deep venous drainage, and LED). Full Score combines the variables in the Spetzler-Martin (S-M) grading system (nidus size, eloquence of adjacent brain, and venous drainage) and the HDVL. For the third grading system, the fS-M grading system, the authors added information regarding eloquent fiber tracts to the S-M grading system. The area under the receiver operating characteristic (ROC) curves was compared with those of the S-M grading system and the supplementary S-M grading system of Lawton et al.RESULTSLED was significantly correlated with a change in mRS score (p < 0.001). An LED of 4.95 mm was the cutoff point for the worsened mRS score. Hemorrhagic presentation, diffuseness, deep venous drainage, and LED were independent predictors of a change in mRS score. Predictive accuracy was highest for the HDVL grading system (area under the ROC curve 0.82), followed by the Full Score grading system (0.80), the fS-M grading system (0.79), the supplementary S-M grading system (0.76), and least for the S-M grading system (0.71). Predictive accuracy of the HDVL grading system was significantly better than that of the Spetzler-Martin grade (p = 0.040).CONCLUSIONSLED was a significant predictor for the preoperative risk evaluation for surgery. The HDVL system was a good predictor of neurological outcomes after BAVM surgery. Adding the consideration of the involvement of eloquent fiber tracts to preoperative evaluation can effectively improve its predictive accuracy.
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Zhang, Yi, Jing-jing Li, Bo Luo, Xiao-fei Guo, Jian-xin Liu, and Shun-shi Yang. "DNAJC3-AS1 Is Associated with Proliferation, Metastasis, and Poor Prognosis of Breast Cancer." Disease Markers 2021 (November 3, 2021): 1–8. http://dx.doi.org/10.1155/2021/3443474.
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Objective. Long noncoding RNA DNAJC3-AS1 (DNAJC3-AS1) was a newly identified tumor-related lncRNA. The aim of the present study was to explore the prognostic value and diagnostic of DNAJC3-AS1 (DNAJC3-AS1) expression in breast cancer (BC) patients. Patients and Methods. The expression of DNAJC3-AS1 was detected in 170 BC tissues and matched normal breast samples by qRT-PCR. The diagnostic value of DNAJC3-AS1 was examined by receiver-operating characteristic (ROC) assays. The correlation of DNAJC3-AS1 with clinicopathological features and prognosis was also statistically analyzed. CCK-8 assays, colony formation assays, and Transwell assays were applied to examine the potential function of DNAJC3-AS1 on tumor progression. Western blot was used to examine the expression of EMT-related proteins. Results. The expression of DNAJC3-AS1 in BC specimens was higher than that in the adjacent nontumor tissues ( p < 0.01 ). Diagnostic assays revealed that DNAJC3-AS1 has considerable diagnostic accuracy, with an area under the ROC curve (AUC) of 0.7457 ( p < 0.001 ). High DNAJC3-AS1 expression was positively associated with lymph node metastasis ( p = 0.010 ) and clinical stage ( p = 0.023 ). A survival study revealed that patients with high DNAJC3-AS1 expression had shorter overall survival ( p = 0.0067 ) and disease-free survival ( p < 0.0001 ) than those with low DNAJC3-AS1 expression. More importantly, multivariate assays indicated that DNAJC3-AS1 was an independent prognostic factor in BC patients. Functional assays confirmed that silence of DNAJC3-AS1 distinctly suppressed the proliferation, metastasis, and EMT progress of BC cells. Conclusions. DNAJC3-AS1 may be a prognostic and diagnostic biomarker for BC patients.
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Chen, H., A. Karion, C. W. Rella, J. Winderlich, C. Gerbig, A. Filges, T. Newberger, C. Sweeney, and P. P. Tans. "Accurate measurements of carbon monoxide in humid air using the cavity ring-down spectroscopy (CRDS) technique." Atmospheric Measurement Techniques 6, no. 4 (April 17, 2013): 1031–40. http://dx.doi.org/10.5194/amt-6-1031-2013.
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Abstract. Accurate measurements of carbon monoxide (CO) in humid air have been made using the cavity ring-down spectroscopy (CRDS) technique. The measurements of CO mole fractions are determined from the strength of its spectral absorption in the near-infrared region (~1.57 μm) after removing interferences from adjacent carbon dioxide (CO2) and water vapor (H2O) absorption lines. Water correction functions that account for the dilution and pressure-broadening effects as well as absorption line interferences from adjacent CO2 and H2O lines have been derived for CO2 mole fractions between 360–390 ppm and for reported H2O mole fractions between 0–4%. The line interference corrections are independent of CO mole fractions. The dependence of the line interference correction on CO2 abundance is estimated to be approximately −0.3 ppb/100 ppm CO2 for dry mole fractions of CO. Comparisons of water correction functions from different analyzers of the same type show significant differences, making it necessary to perform instrument-specific water tests for each individual analyzer. The CRDS analyzer was flown on an aircraft in Alaska from April to November in 2011, and the accuracy of the CO measurements by the CRDS analyzer has been validated against discrete NOAA/ESRL flask sample measurements made on board the same aircraft, with a mean difference between integrated in situ and flask measurements of −0.6 ppb and a standard deviation of 2.8 ppb. Preliminary testing of CRDS instrumentation that employs improved spectroscopic model functions for CO2, H2O, and CO to fit the raw spectral data (available since the beginning of 2012) indicates a smaller water vapor dependence than the models discussed here, but more work is necessary to fully validate the performance. The CRDS technique provides an accurate and low-maintenance method of monitoring the atmospheric dry mole fractions of CO in humid air streams.
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Salvadori, Simone, Mauro Carnevale, Alessia Fanciulli, and Francesco Montomoli. "Uncertainty Quantification of Non-Dimensional Parameters for a Film Cooling Configuration in Supersonic Conditions." Fluids 4, no. 3 (August 10, 2019): 155. http://dx.doi.org/10.3390/fluids4030155.
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In transonic high-pressure turbine stages, oblique shocks originating from vane trailing edges impact the suction side of each adjacent vane. High-pressure vanes are cooled to tolerate the combustor exit-temperature levels, then it is highly probable that shock impingement will occur in proximity to a row of cooling holes. The presence of such a shock, together with the inevitable manufacturing deviations, alters the location of the shock impingement and of the performance parameters of each cooling hole. The present work provides a general description of the aero-thermal field that occurs on the rear suction side of a cooled vane. Computational Fluid Dynamics (CFD) is used to evaluate the deterministic response of the selected configurations in terms of adiabatic effectiveness, discharge coefficient, blowing ratio, density ratio, and momentum ratio. Turbulence is modelled by using both the Shear Stress Transport method (SST) and the Reynolds Stress Model (RSM) implemented in ANSYS ® FLUENT ® . The obtained results are compared with the experimental data obtained by the Institut für Thermische Strömungsmaschinen in Karlsruhe. Two uncertainty quantification methodologies based on Hermite polynomials and Padè–Legendre approximants are used to consider the probability distribution of the geometrical parameters and to evaluate the response surfaces for the system response quantities. Trailing-edge and cooling-hole diameters have been considered to be aleatory unknowns. Uncertainty quantification analysis allows for the assessment of the mutual effects on global and local parameters of the cooling device. Obtained results demonstrate that most of the parameters are independent by the variation of the aleatory unknowns while the standard deviation of the blowing ratio associated with the hole diameter uncertainty is around 12 % , with no impact by the trailing-edge thickness. No relevant advantages are found using either SST model or RSM in combination with Hermite polynomials and Padè–Legendre approximants.
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Boos, Johannes, Lino Morris Sawicki, Rotem Shlomo Lanzman, Christoph Thomas, Joel Aissa, Christoph Schleich, Philipp Heusch, Gerald Antoch, and Patric Kröpil. "Metal artifact reduction (MAR) based on two-compartment physical modeling: evaluation in patients with hip implants." Acta Radiologica 58, no. 1 (July 19, 2016): 70–76. http://dx.doi.org/10.1177/0284185116633911.
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Background Artifacts from metallic implants can hinder image interpretation in computed tomography (CT). Image quality can be improved using metal artifact reduction (MAR) techniques. Purpose To evaluate the impact of a MAR algorithm on image quality of CT examinations in comparison to filtered back projection (FBP) in patients with hip prostheses. Material and Methods Twenty-two patients with 25 hip prostheses who underwent clinical abdominopelvic CT on a 64-row CT were included in this retrospective study. Axial images were reconstructed with FBP and five increasing MAR levels (M30–34). Objective artifact strength (OAS) (SIart-SInorm) was assessed by region of interest (ROI) measurements in position of the strongest artifact (SIart) and in an osseous structure without artifact (SInorm) (in Hounsfield units [HU]). Two independent readers evaluated subjective image quality regarding metallic hardware, delineation of bone, adjacent muscle, and pelvic organs on a 5-point scale (1, non-diagnostic; 5, excellent image quality). Artifacts in the near field, far field, and newly induced artifacts due to the MAR technique were analyzed. Results OAS values were: M34: 243.8 ± 155.4 HU; M33: 294.3 ± 197.8 HU; M32: 340.5 ± 210.1 HU; M31: 393.6 ± 225.2 HU; M30: 446.8 ± 224.2 HU and FBP: 528.9 ± 227.7 HU. OAS values were significantly lower for M32–34 compared to FBP ( P < 0.01). For overall subjective image quality, results were: FBP, 2.0 ± 0.2; M30, 2.3 ± 0.8; M31, 2.6 ± 0.5; M32, 3.0 ± 0.6; M33, 3.5 ± 0.6; and M34, 3.8 ± 0.4 ( P < 0.001 for M30–M34 vs. FBP, respectively). Increasing MAR levels resulted in new artifacts in 17% of reconstructions. Conclusion The investigated MAR algorithm led to a significant reduction of artifacts from metallic hip implants. The highest MAR level provided the least severe artifacts and the best overall image quality.
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Boys, Emma, Jia (Jenny) Liu, Zhaoxiang Cai, Zainab Noor, Karen L. Mackenzie, Adel Aref, Erin Sykes, et al. "Pan-cancer diagnostic proteomic signature of tissue-of-origin (TOO) using data-independent acquisition mass spectrometry (DIA-MS) from 1289 human tissue samples." Journal of Clinical Oncology 41, no. 16_suppl (June 1, 2023): 3120. http://dx.doi.org/10.1200/jco.2023.41.16_suppl.3120.
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3120 Background: Accurate tumour classification based upon tissue of origin (TOO) remains important to guide treatment selection and prognosis but can be challenging in patients with poorly differentiated malignancy, cancer of unknown primary (CUP) or those with prior malignancy. Data-independent acquisition mass spectrometry (DIA-MS)-based proteomics is emerging as a potential clinical diagnostic and prognostic tool. We aimed to develop a protein-based signature to identify histological subtype and adenocarcinoma TOO using DIA-MS data obtained from a pan-cancer study of human tissue samples as an adjunct to histopathological assessment in challenging clinical scenarios. Methods: We performed DIA-MS-based proteomic profiling of 795 fresh frozen tumour and 494 tumour-adjacent normal samples from the Victorian Cancer Biobank in a clinically orientated workflow. We filtered the cohort to include tumour types relevant to CUP. Protein quantification was derived from raw peptide intensity data. Random forest classifiers to identify histological subtype and adenocarcinoma TOO were subsequently trained and tested using 70% and 30% of the data respectively. Evaluation metrics included top-k accuracy (predicting how often the correct class is among the top k predicted classes) and area under the receiver operating curve (AUROC) (one-versus-rest) ± 95% confidence interval. Results: The final tumour cohort consisted of 427 tumour samples representing eight histological subtypes (adenocarcinoma, germ cell tumour, lymphoma, melanoma, renal cell carcinoma, sarcoma, squamous cell carcinoma, thyroid carcinoma) and seven adenocarcinoma TOO (breast, colorectal, liver, lung, ovary, pancreas, prostate). From 9,051 quantified proteins, 83 were identified with potential utility at identifying histological subtype and adenocarcinoma TOO for use in machine learning models. The histological subtype model identified cancer subtype in the test set with top-1 and top-2 accuracy of 0.95 ± 0.03 and 0.98 ± 0.02 respectively. Average test AUROC over all cancer types (n=8) was 0.98 ± 0.02. The adenocarcinoma TOO model identified tumour TOO in the test set with top-1 and top 2- accuracy of 0.88 ± 0.07 and 0.95 ± 0.04 respectively. Average test AUROC over all adenocarcinoma TOO (n=7) was 0.97 ± 0.02. Conclusions: Our clinically orientated DIA-MS-based proteomic workflow and supervised machine learning can identify protein signatures that classify histological subtype and TOO in tumour samples with high accuracy. This technology may assist diagnostic classification of cancer in challenging clinical scenarios, such as CUP.
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Liu, Yong, Zhaofei Pang, Xiaogang Zhao, Yukai Zeng, Hongchang Shen, and Jiajun Du. "Prognostic model of AU-rich genes predicting the prognosis of lung adenocarcinoma." PeerJ 9 (October 8, 2021): e12275. http://dx.doi.org/10.7717/peerj.12275.
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Background AU-rich elements (ARE) are vital cis-acting short sequences in the 3’UTR affecting mRNA stability and translation. The deregulation of ARE-mediated pathways can contribute to tumorigenesis and development. Consequently, ARE-genes are promising to predict prognosis of lung adenocarcinoma (LUAD) patients. Methods Differentially expressed ARE-genes between LUAD and adjacent tissues in TCGA were investigated by Wilcoxon test. LASSO and Cox regression analyses were performed to identify a prognostic genetic signature. The genetic signature was combined with clinicopathological features to establish a prognostic model. LUAD patients were divided into high- and low-risk groups by the model. Kaplan–Meier curve, Harrell’s concordance index (C-index), calibration curves and decision curve analyses (DCA) were used to assess the model. Function enrichment analysis, immunity and tumor mutation analyses were performed to further explore the underlying molecular mechanisms. GEO data were used for external validation. Results Twelve prognostic genes were identified. The gene riskScore, age and stage were independent prognostic factors. The high-risk group had worse overall survival and was less sensitive to chemotherapy and radiotherapy (P < 0.01). C-index and calibration curves showed good performance on survival prediction in both TCGA (1, 3, 5-year ROC: 0.788, 0.776, 0.766) and the GSE13213 validation cohort (1, 3, 5-year ROC: 0.781, 0.811, 0.734). DCA showed the model had notable clinical net benefit. Furthermore, the high-risk group were enriched in cell cycle, DNA damage response, multiple oncological pathways and associated with higher PD-L1 expression, M1 macrophage infiltration. There was no significant difference in tumor mutation burden (TMB) between high- and low-risk groups. Conclusion ARE-genes can reliably predict prognosis of LUAD and may become new therapeutic targets for LUAD.
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Li, Li, Yundi Cao, YingRui Fan, and Rong Li. "Gene signature to predict prognostic survival of hepatocellular carcinoma." Open Medicine 17, no. 1 (January 1, 2022): 135–50. http://dx.doi.org/10.1515/med-2021-0405.
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Abstract Hepatocellular carcinoma (HCC) has a high incidence and poor prognosis and is the second most fatal cancer, and certain HCC patients also show high heterogeneity. This study developed a prognostic model for predicting clinical outcomes of HCC. RNA and microRNA (miRNA) sequencing data of HCC were obtained from the cancer genome atlas. RNA dysregulation between HCC tumors and adjacent normal liver tissues was examined by DESeq algorithms. Survival analysis was conducted to determine the basic prognostic indicators. We identified competing endogenous RNA (ceRNA) containing 15,364 pairs of mRNA–long noncoding RNA (lncRNA). An imbalanced ceRNA network comprising 8 miRNAs, 434 mRNAs, and 81 lncRNAs was developed using hypergeometric test. Functional analysis showed that these RNAs were closely associated with biosynthesis. Notably, 53 mRNAs showed a significant prognostic correlation. The least absolute shrinkage and selection operator’s feature selection detected four characteristic genes (SAPCD2, DKC1, CHRNA5, and UROD), based on which a four-gene independent prognostic signature for HCC was constructed using Cox regression analysis. The four-gene signature could stratify samples in the training, test, and external validation sets (p <0.01). Five-year survival area under ROC curve (AUC) in the training and validation sets was greater than 0.74. The current prognostic gene model exhibited a high stability and accuracy in predicting the overall survival (OS) of HCC patients.
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Müller, Sören, and Katharina Nowak. "Exploring the miRNA-mRNA Regulatory Network in Clear Cell Renal Cell Carcinomas by Next-Generation Sequencing Expression Profiles." BioMed Research International 2014 (2014): 1–11. http://dx.doi.org/10.1155/2014/948408.
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Altered microRNA (miRNA) expression is a hallmark of many cancer types. The combined analysis of miRNA and messenger RNA (mRNA) expression profiles is crucial to identifying links between deregulated miRNAs and oncogenic pathways. Therefore, we investigated the small non-coding (snc) transcriptomes of nine clear cell renal cell carcinomas (ccRCCs) and adjacent normal tissues for alterations in miRNA expression using a publicly available small RNA-Sequencing (sRNA-Seq) raw-dataset. We constructed a network of deregulated miRNAs and a set of differentially expressed genes publicly available from an independent study toin silicodetermine miRNAs that contribute to clear cell renal cell carcinogenesis. From a total of 1,672 sncRNAs, 61 were differentially expressed across all ccRCC tissue samples. Several with known implications in ccRCC development, like the upregulated miR-21-5p, miR-142-5p, as well as the downregulated miR-106a-5p, miR-135a-5p, or miR-206. Additionally, novel promising candidates like miR-3065, whichi.a.targetsNRP2andFLT1, were detected in this study. Interaction network analysis revealed pivotal roles for miR-106a-5p, whose loss might contribute to the upregulation of 49 target mRNAs, miR-135a-5p (32 targets), miR-206 (28 targets), miR-363-3p (22 targets), and miR-216b (13 targets). Among these targets are the angiogenesis, metastasis, and motility promoting oncogenesc-MET,VEGFA,NRP2, andFLT1, the latter two coding for VEGFA receptors.
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Ying, Jianming, Weihua Li, Kaihua Liu, Cong Xiao, Shuyu Wu, Hua Bao, Xue Wu, Xiaonan Wang, and Yang Shao. "DNA methylation signatures predicting liver metastasis of colorectal cancer: A proof-of-concept pilot study." Journal of Clinical Oncology 38, no. 15_suppl (May 20, 2020): e16080-e16080. http://dx.doi.org/10.1200/jco.2020.38.15_suppl.e16080.
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e16080 Background: Liver metastasis (LIM) is the leading cause of death in colorectal cancer (CRC) patients. Early detection of LIM may improve outcome in CRC patients. The aim of this study was to evaluate the feasibility of predicting LIM of CRC using methylation profiles. Methods: We performed Roche targeted (~5.5 million methylation sites) bisulfite sequencing of matched primary, metastatic and their adjacent normal tissue samples from 5 CRC patients with LIM, 5 patients with lung metastasis (LUM) and 8 patients without metastasis in the training cohort (n = 48 samples). Differential methylation regions (DMR) of LUM were identified and a predictive model was developed. The model was further validated in primary tumor sample from nine patients (6 with LIM). Results: By comparing primary tumor vs adjacent normal tissues and metastatic tumor vs adjacent normal tissues in CRC patients with LIM, we identified 28954 common DMRs which indicating the methylation characteristic of CRC with LIM. Similarly, 16187 DMRs were identified in patients with LUM. 9179 DMRs are shared in both LIM and LUM comparisons which should be the common characteristic of CRC tumor tissue regardless of the location of metastasis. 7008 DMRs are LUM specific and 19775 DMRs are LIM specific. In order to predict LIM in primary, early changes in LIM specific DMRs should be identified. Hence, we further selected 4134 DMRs by chossing significantly differentically methylated regions between LIM primary tissues and LUM primary tissues. To increase the ability of distinguishing LIM from other normal tissues and non-matastasis CRC tumors, 1215 DMRs were finally selected which also showed increasing or decreasing trend of methylation level through the progression of CRC. The final 1215 biomarkers were used to construct a random forest model using methlylation profile of 5 CRC patients with LIM as positive training data and 5 CRC patients with LUM as well as 8 patients without metastasis as negative training data. Through the feature recursive elimination method, one methylation site (chr8.72468901-72469000) was identified with ROC of 0.9 in the training dataset. The predictive model was validated in an independent dataset which is composed of 6 patients with LIM and 3 patients without metastasis, and achieved an AUC of 0.87. Conclusions: Our findings demonstrate the utility of methylation biomarkers for the molecular characterization of metastatic precursors, with implications for prediction and early detection of liver metastasis in CRC.
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Xie, Jian, Yang Peng, Xiaoyu Chen, Qigang Li, Bin Jian, Zelin Wen, and Shengchun Liu. "LACTB mRNA expression is increased in pancreatic adenocarcinoma and high expression indicates a poor prognosis." PLOS ONE 16, no. 1 (January 28, 2021): e0245908. http://dx.doi.org/10.1371/journal.pone.0245908.
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This study aimed to find the prognostic value of Beta-lactamase-like (LACTB) in pancreatic adenocarcinoma (PAAD) patients. The mRNA expression of LACTB was upregulated in PAAD and was correlated with vital status (P = 0.0199). The immunoreactive scores of LACTB protein in human PAAD tissues were significantly higher than those in adjacent noncancerous pancreatic tissues. Receiver operating characteristic (ROC) curve assessment showed that LACTB mRNA expression has high diagnostic value in PAAD. Kaplan-Meier curve and Cox analyses suggested that patients with high LACTB mRNA expression have a poor prognosis, indicating that LACTB mRNA is an independent prognostic factor for overall survival [hazard ratio (HR) = 1.72, P = 0.015, 95% confidence interval (CI) = 1.106–2.253] and disease-specific survival (HR = 1.97, P = 0.004, 95% CI = 1.238–3.152) of PAAD patients. Gene set enrichment analysis (GSEA) revealed that hallmark_g2m_checkpoint, hallmark_myc_targets_v1, hallmark_e2f_targets, and kegg_cell_cycle were differentially enriched in phenotypes with high LACTB expression. In addition, CDC20, CDK4, MCM6, MAD2L1, MCM2 and MCM5 were leading genes intersecting in these four pathways, and a positive correlation between mRNA expression and LACTB was observed in most normal and cancer tissues. Finally, elevated LACTB mRNA expression was significantly related to multiple immune marker sets. Our results elucidate that LACTB is involved in the development of cancer, and that high LACTB expression in patients with PAAD can predict a poor prognosis. High LACTB expression was significantly correlated with cell cycle-related genes and multiple immune marker sets.