Effect of twist level and twist direction of core (double) yarn on dref-3 spun yarn

In this study, an attempt has been made to understand the behaviour of friction spun yarn by introducing doubled yarns as core with diversity in twist level and direction. ‘Z’ twisted 15tex (40s Ne) parent yarn has been used for doubling purposes. To examine the effect of doubling, three twist levels are chosen, viz. 50, 60 and 70 % of the parent yarn twist for both the directions viz. S and Z. Thus, six samples of doubled yarns are prepared. These samples are tested for the count, twist, breaking force and elongation. These yarns are introduced as core into DREF-3 friction spinning system; keeping the sheath fibre constant viz. combed cotton sliver of 0.15 hank for all the samples. The twist direction of the doubled yarn used as core is found to be the influential factor for the breaking force and elongation of the friction spun yar

Localized States at Zigzag Edges of Multilayer Graphene and Graphite Steps

We report the existence of zero energy surface states localized at zigzag edges of $N$-layer graphene. Working within the tight-binding approximation, and using the simplest nearest-neighbor model, we derive the analytic solution for the wavefunctions of these peculiar surface states. It is shown that zero energy edge states in multilayer graphene can be divided into three families: (i) states living only on a single plane, equivalent to surface states in monolayer graphene; (ii) states with finite amplitude over the two last, or the two first layers of the stack, equivalent to surface states in bilayer graphene; (iii) states with finite amplitude over three consecutive layers. Multilayer graphene edge states are shown to be robust to the inclusion of the next nearest-neighbor interlayer hopping. We generalize the edge state solution to the case of graphite steps with zigzag edges, and show that edge states measured through scanning tunneling microscopy and spectroscopy of graphite steps belong to family (i) or (ii) mentioned above, depending on the way the top layer is cut.Comment: 6 pages, 4 figure

Evaluation of Important Treatment Parameters in Supraphysiological Thermal Therapy of Human Liver Cancer HepG2 Cells

This study was aimed at simulating the effect of various treatment parameters like heating rate (HR), peak temperature (PT) and hold/total treatment time on the viability of human liver cancer HepG2 cells subjected to different thermal therapy conditions. The problem was approached by investigating the injury kinetics obtained using experimentally measured viability of the cells, heated to temperatures of 50–70°C for 0–9 min at HRs of 100, 200, 300 and 525°C min(−1). An empirical expression obtained between the activation energy (E) and HR was extended to obtain the E values over a broad range of HRs from 5 to 600°C min(−1) that mimic the actual conditions encountered in a typical thermal therapy protocol. Further, the effect of the HR (5–600°C min(−1)) and PT (50–85°C) on the cell survival was studied over a range of hold times. A significant drop in survival from 90% to 0% with the simultaneous increase in HR and PT was observed as the hold time increased from 0 to 5 min. For complete cell death, the hold time increased with the increase in the HR for a given PT, while the total time showed presence of minima for 60, 65 and 70°C at HRs of 50, 100 and 200°C min(−1), respectively

TGF-beta 1 induces human alveolar epithelial to mesenchymal cell transition (EMT)

Background: Fibroblastic foci are characteristic features in lung parenchyma of patients with idiopathic pulmonary fibrosis (IPF). They comprise aggregates of mesenchymal cells which underlie sites of unresolved epithelial injury and are associated with progression of fibrosis. However, the cellular origins of these mesenchymal phenotypes remain unclear. We examined whether the potent fibrogenic cytokine TGF-β1 could induce epithelial mesenchymal transition (EMT) in the human alveolar epithelial cell line, A549, and investigated the signaling pathway of TGF-β1-mediated EMT. Methods: A549 cells were examined for evidence of EMT after treatment with TGF-β1. EMT was assessed by: morphology under phase-contrast microscopy; Western analysis of cell lysates for expression of mesenchymal phenotypic markers including fibronectin EDA (Fn-EDA), and expression of epithelial phenotypic markers including E-cadherin (E-cad). Markers of fibrogenesis, including collagens and connective tissue growth factor (CTGF) were also evaluated by measuring mRNA level using RT-PCR, and protein by immunofluorescence or Western blotting. Signaling pathways for EMT were characterized by Western analysis of cell lysates using monoclonal antibodies to detect phosphorylated Erk1/2 and Smad2 after TGF-β1 treatment in the presence or absence of MEK inhibitors. The role of Smad2 in TGF-β1-mediated EMT was investigated using siRNA. Results: The data showed that TGF-β1, but not TNF-α or IL-1β, induced A549 cells with an alveolar epithelial type II cell phenotype to undergo EMT in a time-and concentration-dependent manner. The process of EMT was accompanied by morphological alteration and expression of the fibroblast phenotypic markers Fn-EDA and vimentin, concomitant with a downregulation of the epithelial phenotype marker E-cad. Furthermore, cells that had undergone EMT showed enhanced expression of markers of fibrogenesis including collagens type I and III and CTGF. MMP-2 expression was also evidenced. TGF-β1-induced EMT occurred through phosphorylation of Smad2 and was inhibited by Smad2 gene silencing; MEK inhibitors failed to attenuate either EMT-associated Smad2 phosphorylation or the observed phenotypic changes. Conclusion: Our study shows that TGF-β1 induces A549 alveolar epithelial cells to undergo EMT via Smad2 activation. Our data support the concept of EMT in lung epithelial cells, and suggest the need for further studies to investigate the phenomenon

Photoreversible interconversion of a phytochrome photosensory module in the crystalline state.

A major barrier to defining the structural intermediates that arise during the reversible photointerconversion of phytochromes between their biologically inactive and active states has been the lack of crystals that faithfully undergo this transition within the crystal lattice. Here, we describe a crystalline form of the cyclic GMP phosphodiesterases/adenylyl cyclase/FhlA (GAF) domain from the cyanobacteriochrome PixJ in Thermosynechococcus elongatus assembled with phycocyanobilin that permits reversible photoconversion between the blue light-absorbing Pb and green light-absorbing Pg states, as well as thermal reversion of Pg back to Pb. The X-ray crystallographic structure of Pb matches previous models, including autocatalytic conversion of phycocyanobilin to phycoviolobilin upon binding and its tandem thioether linkage to the GAF domain. Cryocrystallography at 150 K, which compared diffraction data from a single crystal as Pb or after irradiation with blue light, detected photoconversion product(s) based on Fobs - Fobs difference maps that were consistent with rotation of the bonds connecting pyrrole rings C and D. Further spectroscopic analyses showed that phycoviolobilin is susceptible to X-ray radiation damage, especially as Pg, during single-crystal X-ray diffraction analyses, which could complicate fine mapping of the various intermediate states. Fortunately, we found that PixJ crystals are amenable to serial femtosecond crystallography (SFX) analyses using X-ray free-electron lasers (XFELs). As proof of principle, we solved by room temperature SFX the GAF domain structure of Pb to 1.55-Å resolution, which was strongly congruent with synchrotron-based models. Analysis of these crystals by SFX should now enable structural characterization of the early events that drive phytochrome photoconversion

Gauged Flavor Group with Left-Right Symmetry

We construct an anomaly-free extension of the left-right symmetric model, where the maximal flavor group is gauged and anomaly cancellation is guaranteed by adding new vectorlike fermion states. We address the question of the lowest allowed flavor symmetry scale consistent with data. Because of the mechanism recently pointed out by Grinstein et al. tree-level flavor changing neutral currents turn out to play a very weak constraining role. The same occurs, in our model, for electroweak precision observables. The main constraint turns out to come from WR-mediated flavor changing neutral current box diagrams, primarily K - Kbar mixing. In the case where discrete parity symmetry is present at the TeV scale, this constraint implies lower bounds on the mass of vectorlike fermions and flavor bosons of 5 and 10 TeV respectively. However, these limits are weakened under the condition that only SU(2)_R x U(1)_{B-L} is restored at the TeV scale, but not parity. For example, assuming the SU(2) gauge couplings in the ratio gR/gL approx 0.7 allows the above limits to go down by half for both vectorlike fermions and flavor bosons. Our model provides a framework for accommodating neutrino masses and, in the parity symmetric case, provides a solution to the strong CP problem. The bound on the lepton flavor gauging scale is somewhat stronger, because of Big Bang Nucleosynthesis constraints. We argue, however, that the applicability of these constraints depends on the mechanism at work for the generation of neutrino masses.Comment: 1+23 pages, 1 table, 5 figures. v3: some more textual fixes (main change: discussion of Lepton Flavor Violating observables rephrased). Matches journal versio

Endosialin expression in relation to clinicopathological and biological variables in rectal cancers with a Swedish clinical trial of preoperative radiotherapy

<p>Abstract</p> <p>Background</p> <p>The importance of changes in tumour-associated stroma for tumour initiation and progression has been established. Endosialin is expressed in fibroblasts and pericytes of blood vessels in several types of tumours, and is involved in the progression of colorectal cancer. In order to see whether endosialin was related to radiotherapy (RT) response, and clinicopathological and biological variables, we investigated endosialin expression in rectal cancers from the patients who participated in a Swedish clinical trial of preoperative RT.</p> <p>Methods</p> <p>Endosialin was immunohistochemically examined in normal mucosa, including distant (<it>n </it>= 72) and adjacent (<it>n </it>= 112) normal mucosa, and primary tumours (<it>n </it>= 135). Seventy-three of 135 patients received surgery alone and 62 received additional preoperative RT.</p> <p>Results</p> <p>Endosialin expression in the stroma increased from normal mucosa to tumour (<it>p </it>< 0.0001) both in RT and non-RT group. In the RT group, endosialin expression in the stroma was positively associated with expression of cyclooxygenase-2 (Cox-2) (<it>p </it>= 0.03), p73 (<it>p </it>= 0.01) and phosphates of regenerating liver (PRL) (<it>p </it>= 0.002). Endosialin expression in the tumour cells of both in the RT group (<it>p </it>= 0.01) and the non-RT group (<it>p </it>= 0.06) was observed more often in tumours with an infiltrative growth pattern than in tumours with an expansive growth pattern. In the RT group, endosialin expression in tumour cells was positively related to PRL expression (<it>p </it>= 0.02), whereas in the non-RT group, endosialin expression in tumour cells was positively related to p73 expression (<it>p </it>= 0.01).</p> <p>Conclusions</p> <p>Endosialin expression may be involved in the progression of rectal cancers, and was related to Cox-2, p73 and PRL expression. However, a direct relationship between endosialin expression and RT responses in patients was not found.</p

Functional Diversity and Structural Disorder in the Human Ubiquitination Pathway

The ubiquitin-proteasome system plays a central role in cellular regulation and protein quality control (PQC). The system is built as a pyramid of increasing complexity, with two E1 (ubiquitin activating), few dozen E2 (ubiquitin conjugating) and several hundred E3 (ubiquitin ligase) enzymes. By collecting and analyzing E3 sequences from the KEGG BRITE database and literature, we assembled a coherent dataset of 563 human E3s and analyzed their various physical features. We found an increase in structural disorder of the system with multiple disorder predictors (IUPred - E1: 5.97%, E2: 17.74%, E3: 20.03%). E3s that can bind E2 and substrate simultaneously (single subunit E3, ssE3) have significantly higher disorder (22.98%) than E3s in which E2 binding (multi RING-finger, mRF, 0.62%), scaffolding (6.01%) and substrate binding (adaptor/substrate recognition subunits, 17.33%) functions are separated. In ssE3s, the disorder was localized in the substrate/adaptor binding domains, whereas the E2-binding RING/HECT-domains were structured. To demonstrate the involvement of disorder in E3 function, we applied normal modes and molecular dynamics analyses to show how a disordered and highly flexible linker in human CBL (an E3 that acts as a regulator of several tyrosine kinase-mediated signalling pathways) facilitates long-range conformational changes bringing substrate and E2-binding domains towards each other and thus assisting in ubiquitin transfer. E3s with multiple interaction partners (as evidenced by data in STRING) also possess elevated levels of disorder (hubs, 22.90% vs. non-hubs, 18.36%). Furthermore, a search in PDB uncovered 21 distinct human E3 interactions, in 7 of which the disordered region of E3s undergoes induced folding (or mutual induced folding) in the presence of the partner. In conclusion, our data highlights the primary role of structural disorder in the functions of E3 ligases that manifests itself in the substrate/adaptor binding functions as well as the mechanism of ubiquitin transfer by long-range conformational transitions. © 2013 Bhowmick et al

Intrinsic genetic characteristics determine tumor-modifying capacity of fibroblasts: matrix metalloproteinase-3 5A/5A genotype enhances breast cancer cell invasion

Background Stromal fibroblasts can contribute to tumor invasion through the release of matrix metalloproteinases (MMPs). Population studies have suggested that single nucleotide polymorphisms (SNPs) in MMP genes influence levels of expression and may be associated with breast cancer risk and with disease progression. This study directly examined the impact of MMP SNP genotype on the ability of host fibroblasts to promote tumor cell invasion. Methods Primary breast fibroblasts were isolated from patients with (n = 13) or without (n = 19) breast cancer, and their ability to promote breast cancer cell invasion was measured in in vitro invasion assays. Fibroblast invasion-promoting capacity (IPC) was analyzed in relation to donor type (tumor or non-tumor patient), MMP-1, MMP-3, and MMP-9 SNP genotype and MMP activity using independent samples t test and analysis of variance. All statistical tests were two-sided. Results Tumor-derived fibroblasts promoted higher levels of invasion than normal fibroblasts (p = 0.041). When IPC was related to genotype, higher levels of IPC were generated by tumor fibroblasts with the high-expressing MMP-3 5A/5A genotype compared with the 5A/6A and 6A/6A genotypes (p = 0.05 and 0.07, respectively), and this was associated with enhanced MMP-3 release. The functional importance of MMP-3 was demonstrated by enhanced invasion in the presence of recombinant MMP-3, whereas reduction occurred in the presence of a specific MMP-3 inhibitor. An inverse relationship was demonstrated between fibroblast IPC and the high-expressing MMP-1 genotype (p = 0.031), but no relationship was seen with MMP-9 SNP status. In contrast, normal fibroblasts showed no variation in IPC in relation to MMP genotype, with MMP-3 5A/5A fibroblasts exhibiting significantly lower levels of IPC than their tumor-derived counterparts (p = 0.04). Conclusion This study has shown that tumor-derived fibroblasts exhibit higher levels of IPC than normal fibroblasts and that the MMP-3 5A/5A genotype contributes to this through enhanced MMP-3 release. Despite a high-expressing genotype, normal fibroblasts do not exhibit higher IPC or enhanced MMP release. This suggests that more complex changes occur in tumor-derived fibroblasts, enabling full expression of the MMP SNP genotype and these possibly are epigenetic in nature. The results do suggest that, in women with breast cancer, a high-expressing MMP-3 genotype may promote tumor progression more effectively

Keystone symposium: The role of microenvironment in tumor induction and progression, Banff, Canada, 5–10 February 2005

The first Keystone symposium on the role of microenvironment in tumor induction and progression attracted 274 delegates from 13 countries to Banff in the heart of the Canadian Rockies. The meeting was organized by Mina Bissell, Ronald DePinho and Luis Parada, and was held concurrently with the Keystone symposium on cancer and development, chaired by Matthew Scott and Roeland Nusse. The 30 oral presentations and over 130 posters provided an excellent forum for discussing emerging data in this rapidly advancing field