A Data-Driven Framework for Team Formation for Maintenance Tasks

Even as maintenance evolves with new technologies, it is still a heavily human-driven domain; multiple steps in the maintenance workflow still require human expertise and intervention. Various maintenance activities require multiple maintainers, all with different skill sets and expertise, and from various positions and levels within the organization. Responding to maintenance requests, training exercises, or executing larger maintenance projects all can require maintenance teams. Having the correct assortment of individuals both in terms of skills and management experience can help improve the efficiency of these maintenance tasks. This paper presents a workflow for creating teams of maintainers by adapting accepted practices from the human-computer interaction (HCI) community. These steps provide a low-cost solution to help account for the needs of maintainers and their management, while matching skills of the maintainers with the needs of the activity

Mechanism of resistance to trastuzumab and molecular sensitization via ADCC activation by exogenous expression of HER2-extracellular domain in human cancer cells

Trastuzumab, a humanized antibody targeting HER2, exhibits remarkable therapeutic efficacy against HER2-positive breast and gastric cancers; however, acquired resistance presents a formidable obstacle to long-term tumor responses in the majority of patients. Here, we show the mechanism of resistance to trastuzumab in HER2-positive human cancer cells and explore the molecular sensitization by exogenous expression of HER2-extracellular domain (ECD) in HER2-negative or trastuzumab-resistant human cancer cells. We found that long-term exposure to trastuzumab induced resistance in HER2-positive cancer cells; HER2 expression was downregulated, and antibody-dependent cellular cytotoxicity (ADCC) activity was impaired. We next examined the hypothesis that trastuzumab-resistant cells could be re-sensitized by the transfer of non-functional HER2-ECD. Exogenous HER2-ECD expression induced by the stable transfection of a plasmid vector or infection with a replication-deficient adenovirus vector had no apparent effect on the signaling pathway, but strongly enhanced ADCC activity in low HER2-expressing or trastuzumab-resistant human cancer cells. Our data indicate that restoration of HER2-ECD expression sensitizes HER2-negative or HER2-downregulated human cancer cells to trastuzumab-mediated ADCC, an outcome that has important implications for the treatment of human cancers

Excited-state studies of polyacenes: A comparative picture using EOMCCSD, CR-EOMCCSD(T), range-separated (LR/RT)-TDDFT, TD-PM3, and TD-ZINDO

The low-lying excited states (La and Lb) of polyacenes from naphthalene to heptacene (N = 2-7) are studied using various time-dependent computational approaches. We perform high-level excited-state calculations using equation of motion coupled cluster with singles and doubles (EOMCCSD) and completely renormalized equation of motion coupled cluster with singles, doubles, and perturbative triples (CR-EOMCCSD(T)) and use these results to evaluate the performance of various range-separated exchange-correlation functionals within linear-response (LR) and real-time (RT) time-dependent density functional theories (TDDFT). As has been reported recently, we find that the range-separated family of functionals addresses the well-documented TDDFT failures in describing these low-lying singlet excited states to a large extent and are as about as accurate as results from EOMCCSD on average. Real-time TDDFT visualization shows that the excited state charged densities are consistent with the predictions of the perimeter free electron orbital (PFEO) model. This corresponds to particle-on-a-ring confinement, which leads to the well-known red-shift of the excitations with acene length. We also use time-dependent semiempirical methods like TD-PM3 and TD-ZINDO, which are capable of handling very large systems. Once reparametrized to match the CR-EOMCCSD(T) results, TD-ZINDO becomes roughly as accurate as range-separated TDDFT, which opens the door to modeling systems such as large molecular assemblies. © 2011 American Chemical Society

Gender-Specific Reduction in Contraction is Associated with Increased Estrogen Receptor Expression in Single Vascular Smooth Muscle Cells of Female Rat

Gender differences in the incidence of cardiovascular disease have been related to plasma estrogen levels; however, the role of vascular estrogen receptor (ER) subtypes in these sex differences is less clear. We tested whether the gender differences in vascular smooth muscle (VSM) function reflect differential expression/activity of ERα, ERβ and the newly-identified GPR30. Single aortic VSM cells (VSMCs) were freshly isolated from male and female Sprague-Dawley rats, and their contraction to phenylephrine (PHE, 10(−5) M), Angll (10(−7) M) and membrane-depolarization by KCl (51 mM) was measured in the absence or presence of 10(−6) M 17β-estradiol (E2, stimulant of most ERs), PPT (ERα agonist), DPN (ERβ agonist), and ICI 182,780 (an ERα/ERβ antagonist with GPR30 agonistic properties). The cells were fixed and fluorescently labeled with ERα, ERβ or GPR30 antibody, and the subcellular distribution of ERs was examined using digital imaging microscopy. The mRNA expression and protein amount of aortic ER subtypes was examined using RT-PCR and Western blots. PHE, AngII, and KCl caused less contraction in VSMCs of females than males. Pretreatment of VSMCs with E2 reduced PHE-, AngII- and KCl-induced contraction in both males and females. PPT caused similar inhibition of PHE-, AngII- and KCl-induced contraction as E2, suggesting a role of ERα. DPN mainly inhibited PHE and KCl contraction, suggesting an interaction between ERβ and Ca(2+) channels. ICI 182,780 did not reduce aortic VSMC contraction, suggesting little role for GPR30. RT-PCR and Western blots revealed greater expression of ERα and ERβ in VSMCs of females than males, but similar amounts of GPR30. The total immunofluorescence signal for ERα and ERβ was greater in VSMCs of females than males, and was largely localized in the nucleus. GPR30 fluorescence was similar in VSMCs of males and females, and was mainly in the cytosol. In PPT treated cells, nuclear ERα signal was enhanced. DPN did not affect the distribution of ERβ, and ICI 182,780 did not significantly increase GPR30 in the cell surface. Thus, ER subtypes demonstrate similar responsiveness to specific agonists in VSMCs of male and female rats. The reduced contraction in VSMCs of females could be due to gender-related increase in the expression of ERα and ERβ

Title Page Dissociation of Hyperglycemia from Altered Vascular Contraction and Relaxation Mechanisms in Caveolin-1 Null Mice Running Title Page Running Title: Glycemic and Vascular Dysfunction in Cav-1 Deficiency

cav-1 -/-<WT; endothelium removal, the NOS blocker L-NAME or soluble guanylate cyclase (sGC) inhibitor ODQ enhanced Phe contraction, and metformin blunted this effect. Acetylcholine (ACh)-induced relaxation was in cav-1 -/->WT, abolished by endotheliumremoval, L-NAME or ODQ, and reduced with metformin. NO donor sodium nitroprusside was more potent in inducing relaxation in cav-1 -/-than WT, and metformin reversed this effect. Aortic eNOS, AMPK and sGC were in cav-1 -/->WT, and metformin decreased total and phosphorylated eNOS and AMPK in cav-1 -/-. Thus metformin inhibits both vascular contraction and NO-cGMP-dependent relaxation, but does not affect BP or blood glucose in cav-1 -/-mice, suggesting dissociation of hyperglycemia from altered vascular function in cav-1 deficiency states. JPE

Spoligotyping of Mycobacterium tuberculosis isolates using Luminex®-based method in Lebanon

INTRODUCTION: Data about the genotypes of circulating Mycobacterium tuberculosis isolates (MTB) in Lebanon are scarce. This study was undertaken to reveal the spoligotypes of MTB isolates recovered from patients in Lebanon. METHODOLOGY: MTB isolates from 49 patients living in Lebanon were recovered and identified. The samples were heat killed and subjected to DNA extraction. Spoligotyping was performed using microbeads from TB-SPOL Kit and the fluorescence intensity was measured using Luminex 200®. Generated patterns were assigned to families using the SITVIT2 international database of the Pasteur Institute of Guadeloupe and compared. RESULTS: The spoligotyping of the 49 MTB isolates revealed that 31 isolates belonged to Lineage 4 (Euro-American, 63.3%), 12 to Lineage 3 (East- African Indian, 24.5%), 3 to Lineage 2 (East Asian, 6%) and 2 were unknown. Over half of the genotypes (16 of 30) harbored SIT127 supposed to belong to the L4.5 sublineage. One isolate belonging to the rare Manu-Ancestor SIT523 was recovered for the first time in Lebanon, being associated with highly virulent extensively drug-resistant (XDR) MTB phenotype. CONCLUSION: The application of the Spoligotyping Multiplex Luminex® method is an efficient, discriminatory and rapid method to use for first-lane genotyping of MTB isolates. Though humble numbers were tested, this study is one of the first to describe the genomic diversity and epidemiology of MTB isolates of Lebanon, and suggests an increasing prevalence of SIT127 in the country