Design of a suction-based wall-climbing robot for installing NDT sensors on dry cask storage tanks

Spent Nuclear Fuel (SNF) is contained within welded Dry Storage Canister (DSC), comprised of a stainless-steel canister encased within a concrete overpack, to effectively contain radioactive materials. As the DSC’s lifespan increases, the need for robust, comprehensive inspection and maintenance procedures becomes increasingly critical to detect and mitigate any potential degradation [1]. Traditional certification of DSCs currently relies on periodic visual inspections performed by experts, a method that has potential for enhancement through more frequent or continuous surveillance, paired with more objective and verifiable evaluation measures. Driven by these needs, the Smart Structures Lab, under the leadership of Dr. Salamone, has pioneered an innovative method for scrutinizing the condition of stainless-steel canisters. This approach employs an array of cost-effective piezoelectric sensors adhered to the canister’s surface [2]. This thesis builds upon this work by developing and evaluating a suction-based wall-climbing robot, integrated with a sensor deployment mechanism. The resulting system facilitates sensor installation, thereby enabling long-term, continuous monitoring of the DSC’s condition. This effort focuses on two novel requirements for this task relative to other wall climbing robots: maintaining adhesion with low clearances (< 4”) on non-ferromagnetic curved surfaces and robustly deploying sensors for long-term data collection.Mechanical Engineerin

Differentiation of acute and four-week old myocardial infarct with Gd(ABE-DTTA)-enhanced CMR

<p>Abstract</p> <p>Background</p> <p>Standard extracellular cardiovascular magnetic resonance (CMR) contrast agents (CA) do not provide differentiation between acute and older myocardial infarcts (MI). The purpose of this study was to develop a method for differentiation between acute and older myocardial infarct using myocardial late-enhancement (LE) CMR by a new, low molecular weight contrast agent.</p> <p>Dogs (n = 6) were studied in a closed-chest, reperfused, double myocardial infarct model. Myocardial infarcts were generated by occluding the Left Anterior Descending (LAD) coronary artery with an angioplasty balloon for 180 min, and four weeks later occluding the Left Circumflex (LCx) coronary artery for 180 min. LE images were obtained on day 3 and day 4 after second myocardial infarct, using Gd(DTPA) (standard extracellular contrast agent) and Gd(ABE-DTTA) (new, low molecular weight contrast agent), respectively. Triphenyltetrazolium chloride (TTC) histomorphometry validated existence and location of infarcts. Hematoxylin-eosin and Masson's trichrome staining provided histologic evaluation of infarcts.</p> <p>Results</p> <p>Gd(ABE-DTTA) or Gd(DTPA) highlighted the acute infarct, whereas the four-week old infarct was visualized by Gd(DTPA), but not by Gd(ABE-DTTA). With Gd(ABE-DTTA), the mean ± SD signal intensity enhancement (SIE) was 366 ± 166% and 24 ± 59% in the acute infarct and the four-week old infarct, respectively (P < 0.05). The latter did not differ significantly from signal intensity in healthy myocardium (P = NS). Gd(DTPA) produced signal intensity enhancements which were similar in acute (431 ± 124%) and four-week old infarcts (400 ± 124%, P = NS), and not statistically different from the Gd(ABE-DTTA)-induced SIE in acute infarct. The existence and localization of both infarcts were confirmed by triphenyltetrazolium chloride (TTC). Histologic evaluation demonstrated coagulation necrosis, inflammation, and multiple foci of calcification in the four day old infarct, while the late subacute infarct showed granulation tissue and early collagen deposition.</p> <p>Conclusions</p> <p>Late enhancement CMR with separate administrations of standard extracellular contrast agent, Gd(DTPA), and the new low molecular weight contrast agent, Gd(ABE-DTTA), differentiates between acute and late subacute infarct in a reperfused, double infarct, canine model.</p

beta1A integrin expression is required for type 1 insulin-like growth factor receptor mitogenic and transforming activities and localization to focal contacts

The cells\u27 ability to proliferate in response to growth factor stimulation is significantly altered during cancer progression. To investigate the mechanisms underlying these alterations in prostate cancer, the role and expression of beta1A integrin and type 1 insulin-like growth factor receptor (IGF-IR), known to contribute to cell proliferation and transformation, were analyzed. Using small interfering RNA oligonucleotides to down-regulate beta1A, we show that beta1A expression is required for IGF-IR-mediated prostate cancer cell proliferation and anchorage-independent growth. In vivo, using age-matched transgenic adenocarcinoma of mouse prostate (TRAMP) mice at different stages of prostate cancer [prostatic intraepithelial neoplasia, PIN; well-differentiated adenocarcinoma, WD; and poorly differentiated adenocarcinoma, PD], the expression of beta1A and of IGF-IR was studied. beta1A and IGF-IR expression levels were concurrently up-regulated in high PIN and WD, whereas their expression did not correlate in late-stage PD. In contrast to the up-regulated expression of beta1A, the levels of beta1C, a beta1 cytoplasmic variant that inhibits cell proliferation, were down-regulated in all stages of prostate cancer. A similar expression pattern was observed for a beta1C downstream effector, Grb2-associated binder-1 (Gab1) which is known to inhibit IGF-IR phosphorylation. To analyze in vitro the mechanistic implications of beta1A, beta1C, and Gab1 deregulation in prostate cancer, we investigated whether expression of either beta1 variant in beta1-null cells affected IGF-IR localization. We found that IGF-IR and beta1A were colocalized in highly specialized integrin signaling compartments, designated focal contacts. However, in the presence of beta1C, IGF-IR remained diffuse on the cell surface and did not localize to focal contacts. The findings that beta1 integrins and IGF-IR are concurrently deregulated and that expression of beta1 integrins is necessary to achieve appropriate IGF-IR intracellular distribution point to the important role that the cross-talk between these receptors may have during prostate cancer progression and will be helpful in formulating new therapeutic strategies

MTADV 5-MER peptide suppresses chronic inflammations as well as autoimmune pathologies and unveils a new potential target-Serum Amyloid A.

Despite the existence of potent anti-inflammatory biological drugs e.g., anti-TNF and anti IL-6 receptor antibodies, for treating chronic inflammatory and autoimmune diseases, these are costly and not specific. Cheaper oral available drugs remain an unmet need. Expression of the acute phase protein Serum Amyloid A (SAA) is dependent on release of pro-inflammatory cytokines IL-1, IL-6 and TNF-α during inflammation. Conversely, SAA induces pro-inflammatory cytokine secretion, including Th17, leading to a pathogenic vicious cycle and chronic inflammation. 5- MER peptide (5-MP) MTADV (methionine-threonine-alanine-aspartic acid-valine), also called Amilo-5MER, was originally derived from a sequence of a pro-inflammatory CD44 variant isolated from synovial fluid of a Rheumatoid Arthritis (RA) patient. This human peptide displays an efficient anti-inflammatory effects to ameliorate pathology and clinical symptoms in mouse models of RA, Inflammatory Bowel Disease (IBD) and Multiple Sclerosis (MS). Bioinformatics and qRT-PCR revealed that 5-MP, administrated to encephalomyelytic mice, up-regulates genes contributing to chronic inflammation resistance. Mass spectrometry of proteins that were pulled down from an RA synovial cell extract with biotinylated 5-MP, showed that it binds SAA. 5-MP disrupted SAA assembly, which is correlated with its pro-inflammatory activity. The peptide MTADV (but not scrambled TMVAD) significantly inhibited the release of pro-inflammatory cytokines IL-6 and IL-1β from SAA-activated human fibroblasts, THP-1 monocytes and peripheral blood mononuclear cells. 5-MP suppresses the pro-inflammatory IL-6 release from SAA-activated cells, but not from non-activated cells. 5-MP could not display therapeutic activity in rats, which are SAA deficient, but does inhibit inflammations in animal models of IBD and MS, both are SAA-dependent, as shown by others in SAA knockout mice. In conclusion, 5-MP suppresses chronic inflammation in animal models of RA, IBD and MS, which are SAA-dependent, but not in animal models, which are SAA-independent

AN1284 attenuates steatosis, lipogenesis, and fibrosis in mice with pre-existing non-alcoholic steatohepatitis and directly affects aryl hydrocarbon receptor in a hepatic cell line

Non-alcoholic steatohepatitis (NASH) is an aggressive form of fatty liver disease with hepatic inflammation and fibrosis for which there is currently no drug treatment. This study determined whether an indoline derivative, AN1284, which significantly reduced damage in a model of acute liver disease, can reverse steatosis and fibrosis in mice with pre-existing NASH and explore its mechanism of action. The mouse model of dietary-induced NASH reproduces most of the liver pathology seen in human subjects. This was confirmed by RNA-sequencing analysis. The Western diet, given for 4 months, caused steatosis, inflammation, and liver fibrosis. AN1284 (1 mg or 5 mg/kg/day) was administered for the last 2 months of the diet by micro-osmotic-pumps (mps). Both doses significantly decreased hepatic damage, liver weight, hepatic fat content, triglyceride, serum alanine transaminase, and fibrosis. AN1284 (1 mg/kg/day) given by mps or in the drinking fluid significantly reduced fibrosis produced by carbon tetrachloride injections. In human HUH7 hepatoma cells incubated with palmitic acid, AN1284 (2.1 and 6.3 ng/ml), concentrations compatible with those in the liver of mice treated with AN1284, decreased lipid formation by causing nuclear translocation of the aryl hydrocarbon receptor (AhR). AN1284 downregulated fatty acid synthase (FASN) and sterol regulatory element-binding protein 1c (SREBP-1c) and upregulated Acyl-CoA Oxidase 1 and Cytochrome P450-a1, genes involved in lipid metabolism. In conclusion, chronic treatment with AN1284 (1mg/kg/day) reduced pre-existing steatosis and fibrosis through AhR, which affects several contributors to the development of fatty liver disease. Additional pathways are also influenced by AN1284 treatment

Role of CFTR in lysosome acidification

The role of CFTR in lysosome acidification was examined in CFPAC-1 pancreatic adenocarcinoma cells with the [Delta]F508 mutation that were transduced with a retroviral vector (PLJ-CFPAC) or with the normal CFTR gene (CFTR-CFPAC). Steady-state lysosomal pHi in intact cells was in PLJ-CFPAC cells than CFTR-CFPAC cells (3.55 vs 3.80) and was not affected by cAMP or forskolin. Initial rates of ATP-dependent acidification of isolated lysosomes and steady-state ATP-dependent pHi were similar in both cell lines over a range of chloride concentrations and were not altered when cells were exposed to cAMP or to forskolin prior to preparation of lysosomes. These observations suggest that CFTR plays no role in acidification of lysosomes, possibly due to limited permeability of lysosomal membranes to chloride.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/30102/1/0000474.pd

Predicting coaxial helical stacking in RNA junctions

RNA junctions are important structural elements that form when three or more helices come together in space in the tertiary structures of RNA molecules. Determining their structural configuration is important for predicting RNA 3D structure. We introduce a computational method to predict, at the secondary structure level, the coaxial helical stacking arrangement in junctions, as well as classify the junction topology. Our approach uses a data mining approach known as random forests, which relies on a set of decision trees trained using length, sequence and other variables specified for any given junction. The resulting protocol predicts coaxial stacking within three- and four-way junctions with an accuracy of 81% and 77%, respectively; the accuracy increases to 83% and 87%, respectively, when knowledge from the junction family type is included. Coaxial stacking predictions for the five to ten-way junctions are less accurate (60%) due to sparse data available for training. Additionally, our application predicts the junction family with an accuracy of 85% for three-way junctions and 74% for four-way junctions. Comparisons with other methods, as well applications to unsolved RNAs, are also presented. The web server Junction-Explorer to predict junction topologies is freely available at: http://bioinformatics.njit.edu/junction

The UA_handle: a versatile submotif in stable RNA architectures†

Stable RNAs are modular and hierarchical 3D architectures taking advantage of recurrent structural motifs to form extensive non-covalent tertiary interactions. Sequence and atomic structure analysis has revealed a novel submotif involving a minimal set of five nucleotides, termed the UA_handle motif (5′XU/ANnX3′). It consists of a U:A Watson–Crick: Hoogsteen trans base pair stacked over a classic Watson–Crick base pair, and a bulge of one or more nucleotides that can act as a handle for making different types of long-range interactions. This motif is one of the most versatile building blocks identified in stable RNAs. It enters into the composition of numerous recurrent motifs of greater structural complexity such as the T-loop, the 11-nt receptor, the UAA/GAN and the G-ribo motifs. Several structural principles pertaining to RNA motifs are derived from our analysis. A limited set of basic submotifs can account for the formation of most structural motifs uncovered in ribosomal and stable RNAs. Structural motifs can act as structural scaffoldings and be functionally and topologically equivalent despite sequence and structural differences. The sequence network resulting from the structural relationships shared by these RNA motifs can be used as a proto-language for assisting prediction and rational design of RNA tertiary structures

The exopolysaccharide of Rhizobium sp. YAS34 is not necessary for biofilm formation on Arabidopsis thaliana and Brassica napus roots but contributes to root colonization

Microbial exopolysaccharides (EPSs) play key roles in plant–microbe interactions, such as biofilm formation on plant roots and legume nodulation by rhizobia. Here, we focused on the function of an EPS produced by Rhizobium sp. YAS34 in the colonization and biofilm formation on non-legume plant roots (Arabidopsis thaliana and Brassica napus). Using random transposon mutagenesis, we isolated an EPS-deficient mutant of strain YAS34 impaired in a glycosyltransferase gene (gta). Wild type and mutant strains were tagged with a plasmid-born GFP and, for the first time, the EPS produced by the wild-type strain was seen in the rhizosphere using selective carbohydrate probing with a fluorescent lectin and confocal laser-scanning microscopy. We show for the fist time that Rhizobium forms biofilms on roots of non-legumes, independently of the EPS synthesis. When produced by strain YAS34 wild type, EPS is targeted at specific parts of the plant root system. Nutrient fluctuations, root exudates and bacterial growth phase can account for such a production pattern. The EPS synthesis in Rhizobium sp. YAS34 is not essential for biofilm formation on roots, but is critical to colonization of the basal part of the root system and increasing the stability of root-adhering soil. Thus, in Rhizobium sp. YAS34 and non-legume interactions, microbial EPS is implicated in root–soil interface, root colonization, but not in biofilm formation

Evolutionary Modeling and Prediction of Non-Coding RNAs in Drosophila

We performed benchmarks of phylogenetic grammar-based ncRNA gene prediction, experimenting with eight different models of structural evolution and two different programs for genome alignment. We evaluated our models using alignments of twelve Drosophila genomes. We find that ncRNA prediction performance can vary greatly between different gene predictors and subfamilies of ncRNA gene. Our estimates for false positive rates are based on simulations which preserve local islands of conservation; using these simulations, we predict a higher rate of false positives than previous computational ncRNA screens have reported. Using one of the tested prediction grammars, we provide an updated set of ncRNA predictions for D. melanogaster and compare them to previously-published predictions and experimental data. Many of our predictions show correlations with protein-coding genes. We found significant depletion of intergenic predictions near the 3′ end of coding regions and furthermore depletion of predictions in the first intron of protein-coding genes. Some of our predictions are colocated with larger putative unannotated genes: for example, 17 of our predictions showing homology to the RFAM family snoR28 appear in a tandem array on the X chromosome; the 4.5 Kbp spanned by the predicted tandem array is contained within a FlyBase-annotated cDNA