IDENTIFICATION OF TISSUE AND CIRCULATING BIOMARKERS FOR PREMALIGNANT AND MALIGNANT LESIONS

Recent advancement in technologies including next-generation sequencing and production-scale throughput qPCR have revolutionized the identification of biomarkers in the epidemiology field. In response to the vast amount of data generated from high-throughput technologies, novel inventions in the computer sciences fields have been applied to analyze these data. The current study demonstrates the application of such technologies in a variety of scenarios. I first described how targeted and whole-exome sequencing were used to identify somatic mutations which marked the differences between colorectal adenomas and adenocarcinomas. A statistical test based on the unique clustering pattern of tumor suppressor genes and oncogenes was employed to locate driver mutations. Random forest algorithm was performed to find somatic mutations which best classify samples into adenoma and adenocarcinoma. 20 important mutated genes (TP53, KRAS, APC, PIK3CA, SMAD4, FBXW7, CTNNB1, SYNE1, CDC27, CSMD1, NRAS, RYR3, NALCN, LRP1B, FAT4, ATM, TMPRSS13, SOX9, CSMD3, MED12) which constantly served to separate adenomas from adenocarcinomas were discovered. The Second project focused on exploring differentially expressed genes (DEG) and pathways enriched with such genes in colorectal adenomas and adenocarcinomas. Fold changes of paired premalignant/malignant lesions compared to normal adjacent tissues from the same patient were analyzed. And the ratio of 20-gene panel found in the first project were also found to differ between colorectal adenomas and cancers. The last project in the dissertation demonstrated the potential for microRNA (miR) in the serum to be used as a non-invasive prognostic factor for non-muscle invasive bladder cancers (NMIBC). With the help from a vast amount of miR profiles, we were able to identify two panels in overall population (miR-16/miR-378 + miR-24/miR-331-3p for recurrence and miR-16/miR-21 + miR-24/miR-375 for progression) and two panels in BCG-treated population (miR-16/miR-378 + miR-24/miR-331-3p for recurrence and miR-16/miR-21 + miR-24/miR-375 for progression). Taken together, these projects showcased the discovery of tissue and circulating biomarkers with cutting-edge technologies. These biomarkers could lead to more informed distribution of limited medical resources for monitoring clinical outcomes as well as the origin for future studies on deciphering the intricate mechanisms underlying tumorigenesis, host response and patient survival

A Novel Energy-Efficient MAC Aware Data Aggregation Routing in Wireless Sensor Networks#

Embedding data-aggregation capabilities into sensor nodes of wireless networks could save energy by reducing redundant data flow transmissions. Existing research describes the construction of data aggregation trees to maximize data aggregation times in order to reduce data transmission of redundant data. However, aggregation of more nodes on the same node will incur significant collisions. These MAC (Media Access Control) layer collisions introduce additional data retransmissions that could jeopardize the advantages of data aggregation. This paper is the first to consider the energy consumption tradeoffs between data aggregation and retransmissions in a wireless sensor network. By using the existing CSMA/CA (Carrier Sense Multiple Access with Collision Avoidance) MAC protocol, the retransmission energy consumption function is well formulated. This paper proposes a novel non-linear mathematical formulation, whose function is to minimize the total energy consumption of data transmission subject to data aggregation trees and data retransmissions. This solution approach is based on Lagrangean relaxation, in conjunction with optimization-based heuristics. From the computational experiments, it is shown that the proposed algorithms could construct MAC aware data aggregation trees that are up to 59% more energy efficient than existing data aggregation algorithms

Tape-Arabidopsis Sandwich - a simpler Arabidopsis protoplast isolation method

<p>Abstract</p> <p>Background</p> <p>Protoplasts isolated from leaves are useful materials in plant research. One application, the transient expression of recombinant genes using <it>Arabidopsis </it>mesophyll protoplasts (TEAMP), is currently commonly used for studies of subcellular protein localization, promoter activity, and <it>in vivo </it>protein-protein interactions. This method requires cutting leaves into very thin slivers to collect mesophyll cell protoplasts, a procedure that often causes cell damage, may yield only a few good protoplasts, and is time consuming. In addition, this protoplast isolation method normally requires a large number of leaves derived from plants grown specifically under low-light conditions, which may be a concern when material availability is limited such as with mutant plants, or in large scale experiments.</p> <p>Results</p> <p>In this report, we present a new procedure that we call the Tape-<it>Arabidopsis </it>Sandwich. This is a simple and fast mesophyll protoplast isolation method. Two kinds of tape (Time tape adhered to the upper epidermis and 3 M Magic tape to the lower epidermis) are used to make a "Tape-<it>Arabidopsis </it>Sandwich". The Time tape supports the top side of the leaf during manipulation, while tearing off the 3 M Magic tape allows easy removal of the lower epidermal layer and exposes mesophyll cells to cell wall digesting enzymes when the leaf is later incubated in an enzyme solution. The protoplasts released into solution are collected and washed for further use. For TEAMP, plasmids carrying a gene expression cassette for a fluorescent protein can be successfully delivered into protoplasts isolated from mature leaves grown under optimal conditions. Alternatively, these protoplasts may be used for bimolecular fluorescence complementation (BiFC) to investigate protein-protein interactions <it>in vivo</it>, or for Western blot analysis. A significant advantage of this protocol over the current method is that it allows the generation of protoplasts in less than 1 hr, and allows TEAMP transfection to be carried out within 2 hr.</p> <p>Conclusion</p> <p>The protoplasts generated by this new Tape-<it>Arabidopsis </it>Sandwich method are suitable for the same range of research applications as those that use the current method, but require less operator skill, equipment and time.</p

High Sensitivity Refractive Index Sensor by D-Shaped Fibers and Titanium Dioxide Nanofilm

This paper presents a high sensitivity liquid refractive index (RI) sensor based on lossy mode resonance (LMR) effect. The D-shaped fibers coated with nanosized titanium dioxide (TiO2) thin film as a sensing head were submerged into different refractive index solutions. The variations in the optical spectrum of the proposed RI sensor with different refractive index solutions were measured. The LMR resonance peaks were used to determine the wavelength shifts with different refractive index solutions. The results show that the optical spectrum peaks shifted towards the longer wavelength side with increasing the refractive index. For the proposed fiber sensing head with a polishing residual thickness of 72 μm, the maximum shift of the absorption peak was 264 nm. The sensitivity of the proposed RI sensor was 4122 nm/RIU for the refractive index range from 1.333 to 1.398

Delay QoS and MAC Aware Energy-Efficient Data-Aggregation Routing in Wireless Sensor Networks

By eliminating redundant data flows, data aggregation capabilities in wireless sensor networks could transmit less data to reduce the total energy consumption. However, additional data collisions incur extra data retransmissions. These data retransmissions not only increase the system energy consumption, but also increase link transmission delays. The decision of when and where to aggregate data depends on the trade-off between data aggregation and data retransmission. The challenges of this problem need to address the routing (layer 3) and the MAC layer retransmissions (layer 2) at the same time to identify energy-efficient data-aggregation routing assignments, and in the meantime to meet the delay QoS. In this paper, for the first time, we study this cross-layer design problem by using optimization-based heuristics. We first model this problem as a non-convex mathematical programming problem where the objective is to minimize the total energy consumption subject to the data aggregation tree and the delay QoS constraints. The objective function includes the energy in the transmission mode (data transmissions and data retransmissions) and the energy in the idle mode (to wait for data from downstream nodes in the data aggregation tree). The proposed solution approach is based on Lagrangean relaxation in conjunction with a number of optimization-based heuristics. From the computational experiments, it is shown that the proposed algorithm outperforms existing heuristics that do not take MAC layer retransmissions and the energy consumption in the idle mode into account

Optimal estimation and control for lossy network: stability, convergence, and performance

In this paper, we study the problems of optimal estimation and control, i.e., the linear quadratic Gaussian (LQG) control, for systems with packet losses but without acknowledgment. Such acknowledgment is a signal sent by the actuator to inform the estimator of the incidence of control packet losses. For such system, which is usually called as a user datagram protocol (UDP)-like system, the optimal estimation is nonlinear and its calculation is time-consuming, making its corresponding optimal LQG problem complicated. We first propose two conditions: 1) the sensor has some computation abilities; and 2) the control command, exerted to the plant, is known to the sensor. For a UDP-like system satisfying these two conditions, we derive the optimal estimation. By constructing the finite and infinite product probability measure spaces for the estimation error covariances (EEC), we give the stability condition for the expected EEC, and show the existence of a measurable function to which the EEC converges in distribution, and propose some practical methods to evaluate the estimation performance. Finally, the LQG controllers are derived, and the conditions for the mean square stability of the closed-loop system are established

Interaction between Granulation and Small-Scale Magnetic Flux Observed by Hinode

We study the relationship between granular development and magnetic field evolution in the quiet Sun. 6 typical cases are displayed to exhibit interaction between granules and magnetic elements, and we have obtained the following results. (1) A granule develops centrosymmetrically when no magnetic flux emerges within the granular cell. (2) A granule develops and splits noncentrosymmetrically while flux emerges at an outer part of the granular cell. (3) Magnetic flux emergence as a cluster of mixed polarities is detected at the position of a granule as soon as the granule breaks up. (4) A dipole emerges accompanying with the development of a granule, and the two elements of the dipole root in the adjacent intergranular lanes and face each other across the granule. Advected by the horizontal granular motion, the positive element of the dipole then cancels with pre-existing negative flux. (5) Flux cancellation also takes place between a positive element, which is advected by granular flow, and its surrounding negative flux. (6) While magnetic flux cancellation takes place at a granular cell, the granule shrinks and then disappears. (7) Horizontal magnetic fields enhance at the places where dipoles emerge and where opposite polarities cancel with each other, but only the horizontal fields between the dipolar elements point orderly from the positive element to the negative one. Our results reveal that granules and small-scale magnetic flux influence each other. Granular flow advects magnetic flux, and magnetic flux evolution suppresses granular development. There exist extremely large Doppler blue-shifts at the site of one cancelling magnetic element. This phenomenon may be caused by the upward flow produced by magnetic reconnection below the photosphere.Comment: 8 figures, 13 pages. RAA, in pres

Preparation of N-, O-, and S-tri-doped biochar through one-pot pyrolysis of poplar and urea formaldehyde and its enhanced removal of tetracycline from wastewater

In this study, biochar was prepared via hybrid doping of N, O, and S by applying one-pot pyrolysis of poplar wood and S-containing urea formaldehyde at 900 °C. Different doping ratios were adopted, and the contents of O, N, and S were in the ranges of 2.78 – 5.56 %, 2.16 – 4.92 %, and 1.42 – 4.98 %, respectively. This hybrid doping significantly enhanced the efficiency of the removal of tetracycline (40 mg/L) from wastewater to 71.84 % in comparison with that attained by using normal poplar biochar (29.45 %). The adsorption kinetics and isotherms indicated that the adsorption process was favorable and was dominated by chemisorption instead of physisorption; the dominant adsorption process may be justified by the existence of abundant functional groups. The adsorption capacity was barely related to the surface area (R2 = 0.478), while it was closely related to the concentration of graphitic N (R2 = 0.985) because graphitic N enhanced the π–π interactions. The adsorption capacity was also highly related to the proportion of oxidized N and oxidized S owing to hydrogen bonding, which may have overlapped with the contribution of O-containing functional groups. This study presents a simple hybrid doping method for biochar modification and provides fundamental insights into the specific effects of O-, N- and S-containing functional groups on the performance of biochar for tetracycline removal

Efficacy and safety of nanohybrids comprising silver nanoparticles and silicate clay for controlling Salmonella infection

Developing effective and safe drugs is imperative for replacing antibiotics and controlling multidrug-resistant microbes. Nanoscale silicate platelet (NSP) and its nanohybrid, silver nanoparticle/NSP (AgNP/NSP), have been developed, and the nanohybrids show a strong and general antibacterial activity in vitro. Here, their efficacy for protecting Salmonella-infected chicks from fatality and septicemia was evaluated. Both orally administrated NSP and AgNP/NSP, but not AgNPs alone, effectively reduced the systemic Salmonella infection and mortality. In addition, quantitative Ag analyses demonstrated that Ag deposition from AgNP/NSP in the intestines was less than that from conventional AgNPs, indicating that the presence of NSP for immobilizing AgNPs reduced Ag accumulation in tissue and improved the safety of AgNPs. These in vivo results illustrated that both NSP and AgNP/NSP nanohybrid represent potential agents for controlling enteric bacterial infections