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Epithelial cell collectives migrate through tissue interfaces and crevices to orchestrate processes of development, tumor invasion, and wound healing. Naturally, traversal of cell collective through confining environments involves crowding due to the narrowing space, which seems tenuous given the conventional inverse relationship between cell density and migration. However, physical transitions required to overcome such epithelial densification for migration across confinements remain unclear. Here, in contiguous microchannels, we show that epithelial (MCF10A) monolayers accumulate higher cell density before entering narrower channels; however, overexpression of breast cancer oncogene +ErbB2 reduced this need for density accumulation across confinement. While wildtype MCF10A cells migrated faster in narrow channels, this confinement sensitivity reduced after +ErbB2 mutation or with constitutively-active RhoA. The migrating collective developed pressure differentials upon encountering microchannels, like fluid flow into narrowing spaces, and this pressure dropped with their continued migration. These transitions of pressure and density altered cell shapes and increased effective temperature, estimated by treating cells as granular thermodynamic system. While +RhoA cells and those in confined regions were effectively warmer, cancer-like +ErbB2 cells remained cooler. Epithelial reinforcement by metformin treatment increased density and temperature differentials across confinement, indicating that higher cell cohesion could reduce unjamming. Our results provide experimental evidence for previously proposed theories of inverse relationship between density and motility-related effective temperature. Indeed, we show across cell lines that confinement increases pressure and effective temperature, which enable migration by reducing density. This physical interpretation of collective cell migration as granular matter could advance our understanding of complex living systems.

Background: Gastric cancer (GC) is the second most prevalent cancer worldwide and the eighth most common cause of tumor-related death in Taiwan. Helminthostachys zeylanica, a flavonoid compound, has anti-inflammatory, immunomodulatory, and anticancer effects. We examined whether an extract of H. zeylanica (E1 and E2) has potential as a treatment for GC. Methods: We investigated the effects (pro-apoptosis, pro-autophagy, and antiproliferation ability) of H. zeylanica-E2 on cell viability in healthy gastric epithelial (GES-1) and GC cells (AGS and BGC823). H. zeylanica-E2 was toxic to GC cells but had little or no toxicity to normal cells. Results: In this study, H. zeylanica-E2 induced apoptosis through caspase 3/7, Bcl-2, Bax, cyclooxygenase-2 (COX-2), and cleaved poly (ADP-ribose) polymerase pathways in GC cells. In addition, it increased autophagy by stimulating autophagy-related protein (ATG)5, ATG7, LC3-I/LC3-II, and inhibiting COX-2 activity in GC cells. We also found that H. zeylanica-E2 exhibited antiproliferation ability through cell cycle arrest in G0/G1 and G2/M and suppressed the migration of GC cells. The anticancer effects of H. zeylanica-E2 in GC cells might be mediated partly through inhibition of tumor necrosis factor-α (TNF-α)-activated proinflammatory cytosolic phospholipase A2 (cPLA2)-COX-2-prostaglandin E2 (PGE2) pathway. Conclusions: Our results suggest that H. zeylanica-E2 has potential as a novel adjunctive agent for the treatment of GC.

Extracorporeal membrane oxygenation (ECMO) is one of the common invasive treatments for the care of critically ill patients with heart failure, respiratory failure, or both. There are two modes of ECMO, namely, veno-venous (VV) and veno-arterial (VA), which have different indications, survival rates, and incidences of complications. This study’s aim was to examine whether depression status differed between patients who had received VV-ECMO or VA-ECMO and had been discharged from the hospital. This was a descriptive, cross-sectional, and correlational study of patients who had been discharged from the hospital at least one month after receiving ECMO at a medical center in northern Taiwan from June 2006 to June 2020 (N = 142). Participants were recruited via convenience and quota sampling. Data were collected in the cardiovascular outpatient department between October 2015–October 2016 (n = 52) and September 2019–August 2020 (n = 90). Participants completed the Hospital Anxiety and Depression Scale–Depression (HADS-D) as a measure of depression status. Post-discharge depression scores for patients who received VV-ECMO (n = 67) was significantly higher (p = 0.018) compared with participants who received VA-ECMO (n = 75). In addition, the mode of ECMO was a predictor of post-discharge depression (p = 0.008) for participants who received VV-ECMO. This study concluded that patients who received VV-ECMO may require greater mental health support. Healthcare professionals should establish a psychological clinical care pathway evaluated by multiple healthcare professionals.

Made available in DSpace on 2019-10-04T12:41:37Z (GMT). No. of bitstreams: 0 Previous issue date: 2019-07-02 National Health and Medical Research Council of Australia Background-The uptake of proven stroke treatments varies widely. We aimed to determine the association of evidence-based processes of care for acute ischemic stroke (AIS) and clinical outcome of patients who participated in the HEADPOST (Head Positioning in Acute Stroke Trial), a multicenter cluster crossover trial of lying flat versus sitting up, head positioning in acute stroke. Methods and Results-Use of 8 AIS processes of care were considered: reperfusion therapy in eligible patients; acute stroke unit care; antihypertensive, antiplatelet, statin, and anticoagulation for atrial fibrillation; dysphagia assessment; and physiotherapist review. Hierarchical, mixed, logistic regression models were performed to determine associations with good outcome (modified Rankin Scale scores 0-2) at 90 days, adjusted for patient and hospital variables. Among 9485 patients with AIS, implementation of all processes of care in eligible patients, or defect-free care, was associated with improved outcome (odds ratio, 1.40; 95% CI, 1.18-1.65) and better survival (odds ratio, 2.23; 95% CI, 1.62-3.09). Defect-free stroke care was also significantly associated with excellent outcome (modified Rankin Scale score 0-1) (odds ratio, 1.22; 95% CI, 1.04-1.43). No hospital characteristic was independently predictive of outcome. Only 1445 (15%) of eligible patients with AIS received all processes of care, with significant regional variations in overall and individual rates. Conclusions-Use of evidence-based care is associated with improved clinical outcome in AIS. Strategies are required to address regional variation in the use of proven AIS treatments. Univ New South Wales, Fac Med, George Inst Global Hlth, Sydney, NSW, Australia Ctr Estudios Clin, Inst Ciencias & Innovac Med, Santiago, Chile Clin Alemana Univ Desarrollo, Fac Med, Serv Neurol, Dept Neurol & Psiquiatria, Santiago, Chile Peking Univ, Hlth Sci Ctr, George Inst Global Hlth, Beijing, Peoples R China Australian Catholic Univ, Nursing Res Inst, St Vincents Hlth Australia Sydney, Sydney, NSW, Australia Univ Cent Lancashire, Fac Hlth & Wellbeing, Preston, Lancs, England Univ Chile, Fac Med, Dept Ciencias Neurol, Santiago, Chile Univ Sao Paulo, Ribeirao Preto Med Sch, Stroke Serv Neurol Div, Ribeirao Preto, Brazil Fukuoka Univ, Fac Med, Dept Prevent Med & Publ Hlth, Fukuoka, Fukuoka, Japan Univ Leicester, Dept Cardiovasc Sci, Leicester Biomed Res Ctr, Leicester, Leics, England Univ Leicester, Natl Inst Hlth Res, Leicester Biomed Res Ctr, Leicester, Leics, England Univ Edinburgh, Ctr Clin Brain Sci, Edinburgh, Midlothian, Scotland George Inst Global Hlth, Sydney, NSW, Australia Univ Desarrollo, Serv Neurol, Dept Neurol & Psiquiatria Clin Alemana Santiago, Santiago, Chile St Vincents Hlth Australia Sydney, Sydney, NSW, Australia Australian Catholic Univ, Sydney, NSW, Australia Univ Cent Lancashire, Stroke Practice Res Unit, Sch Hlth, Lancashire Clin Trials Unit, Preston, Lancs, England Univ Leicester, Dept Cardiovasc Sci, Cardiovasc Res Ctr, British Heart Fdn, Leicester, Leics, England Univ Kelaniya, Dept Pharmacol, Fac Med, Colombo, Sri Lanka Christian Med Coll & Hosp, Dept Neurol, Ludhiana, India Kaohsiung Med Univ & Hosp, Dept Neurol, Kaohsiung, Taiwan Linkou Chang Gung Mem Hosp, Dept Neurol, Taipei, Taiwan Peking Union Med Coll Hosp, Beijing, Peoples R China Univ Sao Paulo, Ribeirao Preto Sch Med, Ribeirao Preto, Brazil Monash Univ, Dept Epidemiol & Prevent Med, Melbourne, Vic, Australia Univ Cent Lancashire, Sch Hlth Sci, Coll Hlth & Wellbeing, Preston, Lancs, England Univ Desarrollo, Santiago, Chile Univ New South Wales, Neurosci Res Australia, Sydney, NSW, Australia Natl Univ Singapore, Dept Pharmacol, Singapore, Singapore Bradford Royal Infirm, Bradford Inst Hlth Res, Leeds, W Yorkshire, England Christian Med College, Ludhiana, Punjab, India RemediumOne Pvt Ltd, Kandy, Sri Lanka Kaohsiung Med Univ, Chung Ho Mem Hosp, Kaohsiung, Taiwan Calvary Publ Hosp Bruce, Bruce, Australia Royal North Shore Hosp, St Leonards, NSW, Australia Royal Prince Alfred Hosp, Camperdown, NSW, Australia Concord Repatriat Gen Hosp, Camperdown, NSW, Australia Fiona Stanley Hosp, Camperdown, NSW, Australia Macquarie Base Hosp, Melbourne, Vic, Australia Univ Sao Paulo, Fac Med Ribeirao Preto, Hosp Clin, Sao Paulo, Brazil Hosp Governador Celso Ramos, Florianopolis, SC, Brazil Sao Paulo State Univ, Hosp Fac Med Botucatu, UNESP, Sao Paulo, Brazil Yangquan Coalmine Grp Gen Hosp, Yangquan, Peoples R China Nanjing Med Univ, Nanjing Hosp 1, Nanjing, Jiangsu, Peoples R China 85 Hosp Peoples Liberat Army, Beijing, Peoples R China Chifeng Univ, Affiliated Hosp, Chifeng, Peoples R China Beijing Pinggu Hosp, Beijing, Peoples R China Wenzhou Med Univ, Affiliated Hosp 1, Wenzhou, Peoples R China Soochow Univ, Affiliated Hosp 2, Suzhou, Peoples R China Hebei Med Univ, Hosp 3, Shijiazhuang, Hebei, Peoples R China Capital Med Univ, Xuanwu Hosp, Beijing, Peoples R China Jining Med Univ, Affiliated Hosp, Jining, Peoples R China Third Peoples Hosp Huizhou, Huizhou, Peoples R China Second Cangzhou Cent Hosp, Cangzhou, Peoples R China Shanghai Jiao Tong Univ, Hosp Affiliated, Sch Med, Shanghai, Peoples R China Baogang Hosp, Baotou, Peoples R China Harbin Med Univ, Affiliated Hosp 1, Harbin, Heilongjiang, Peoples R China Shanghai Jiao Tong Univ Sch, Tong Ren Hosp, Peoples Hosp Hejian City, Shanghai, Peoples R China Peking Univ, Shougang Hosp, Beijing, Peoples R China Guangzhou Med Univ, Affiliated Hosp 3, Guangzhou, Guangdong, Peoples R China Second Hosp Nanchang, Nanchang, Jiangxi, Peoples R China Bethune Int Peace Hosp, Beijing, Peoples R China Hua Henan Prov Peoples Hosp, Beijing, Peoples R China Hua Henan Prov Peoples Hosp, Zhengzhou, Henan, Peoples R China Shanghai Jiao Tong Univ, Sch Med, Shanghai Ninth Peoples Hosp, Shanghai, Peoples R China Shijiazhuang Cent Hosp, Shijiazhuang, Hebei, Peoples R China Hosp Base San Jos de Osorno, Osorno, Chile Christian Med Coll & Hosp, Ludhiana, Punjab, India Unit Narayana Hrudayalaya Ltd, Mazumdar Shaw Med Ctr, Bangalore, Karnataka, India Dr Ramesh Cardiac & Multispecial Hosp Pvt Ltd, Guntur, India Post Grad Inst Med Educ & Res, Chandigarh, India Baby Mem Hosp Ltd, Calicut, Kerala, India Sree Chitra Tirunal Inst Med Sci & Technol, Thiruvananthapuram, Kerala, India Sri Jayawardenepura Gen Hosp, Sri Jayawardenepura Kott, Sri Lanka Colombo North Teaching Hosp, Colombo, Sri Lanka Colombo South Coching Hosp, Colombo, Sri Lanka Linkou Chang Gung Mem Hosp, Taoyuan, Taiwan Taipei Med Univ, Shuang Ho Hosp, Taipei, Taiwan En Chu Kong Hosp, New Taipei, Taiwan Natl Cheng Kung Univ Hosp, Tainan, Taiwan Queen Alexandra Hosp, Portsmouth, Hants, England Portsmouth Hosp NHS Natl Hlth Serv iTrust, Portsmouth, Hants, England Univ Coll London Hosp NHS Fdn Trust, London, England Univ Hosp Birmingham NHS Fdn Trust, Queen Elizabeth Hosp Birmingham, Birmingham, W Midlands, England Southend Univ Hosp NHS Fdn Trust, Southend On Sea, England Kings Coll Hosp London, London, England York Teaching Hosp NHS Fdn Trust, York, N Yorkshire, England Nottingham Univ Hosp NHS Trust, Nottingham, England Blackpool Teaching Hosp NHS Fdn Trust, Blackpool, England Gloucestershire Hosp NHS Fdn Trust, Gloucestershire Royal Hosp, Gloucester, England Teaching Hospi NHS Fdn Trust, London, England Royal Cornwall Hosp NHS Trust, Truro, England Royal London Hosp, Barts Hlth NHS Trust, London, England Sheffield Teaching Hosp NHS Fdn Trust, Sheffield, S Yorkshire, England Cambridge Univ Hosp NHS Fdn Trust, Addenbrookes Hosp, Cambridge, England Royal Victoria Hosp, Belfast Hlth & Social Care Trust, London, England Pinderfields Gen Hosp, Mid Yorkshire Hosp NHS Trust, Wakefield, England Royal Devon & Exeter NHS Fdn Trust, London, England Bradford Teaching Hosp NHS Fdn Trust, Bradford, W Yorkshire, England Great Western Hosp NHS Fdn Trust, Swindon, Wilts, England Watford Dist Gen Hosp, Watford, England Imperial Coll Healthcare NHS Trust, London, England Medway NHS Fdn Trust, Gillingham, England Royal Liverpool & Broadgreen Univ NHS Trust, Liverpool, Merseyside, England Calderdale & Huddersfield NHS Fdn Trust, Huddersfield, W Yorkshire, England Hywel Dda Univ Hlth Board, Haverfordwest, Wales Chesterfield Royal Hosp NHS Fdn Trust, Calow, England Luton & Dunstable Univ Hosp NHS Fdn Trust, Luton, Beds, England Countess Chester Hosp NHS Fdn Trust, Chester, Cheshire, England Peterborough City Hosp, Peterborough, Cambs, England Univ Hosp Leicester NHS Trust, Leicester Royal Infirm, Leicester, Leics, England Dist Hosp NHS Fdn Trust, London, England Barnsley Hosp NHS Fdn Trust, Barnsley, England Dorset Cty Hosp NHS Fdn Trust, Dorchester, England Royal Bournemouth & Christchurch Hosp NHS Fdn Tru, Royal Bournemouth Hosp, Bournemouth, Dorset, England Southern Hlth & Social Care Trust, Craigavon Area Hosp, Portadown, England United Lincolnshire Hosp NHS Trust, Pilgrim Hosp, Lincoln, England Bedford Hosp NHS Trust, Bedford, England Sao Paulo State Univ, Hosp Fac Med Botucatu, UNESP, Sao Paulo, Brazil National Health and Medical Research Council of Australia: 1066966

Loganin, a major iridoid glycoside obtained from fruits of Cornus officinalis, possesses anti-inflammatory, antitumor, antidiabetic, and osteoporosis prevention effects. Loganin has been linked to neuroprotection in several models of neurodegeneration, including Parkinson's disease (PD). However, mechanisms underlying the neuroprotective effects of loganin are still mostly unknown. Here, we demonstrated the protective effects of loganin against PD mimetic toxin 1-methyl-4-phenylpyridinium (MPP+ ) and the important roles of insulin-like growth factor 1 receptor (IGF-1R) and glucagon-like peptide 1 receptor (GLP-1R) in the neuroprotective mechanisms of loganin. In primary mesencephalic neuronal cultures treated with or without MPP+ , loganin up-regulated expressions of neurotrophic signals including IGF-1R, GLP-1R, p-Akt, BDNF, and tyrosine hydroxylase. Loganin protected against MPP+ -induced apoptosis by up-regulating antiapoptotic protein and down-regulating proapoptotic protein. Moreover, loganin attenuated MPP+ -induced neurite damage via up-regulation of GAP43 and down-regulation of membrane-RhoA/ROCK2/p-LIMK/p-cofilin. Loganin also attenuated MPP+ -induced reactive oxygen species (ROS) production. However, both AG1024, an IGF-1R antagonist, and exendin 9-39, a GLP-1R antagonist, attenuated the protective effects of loganin on MPP+ -induced cytotoxicity, apoptosis, neurite length decrease, and ROS production. Our results suggest that loganin attenuates MPP+ -induced apoptotic death, neurite damage, and oxidative stress through enhancement of neurotrophic signaling, activation of IGF-1R/GLP-1R, and inhibition of RhoA/ROCK pathway, providing the evidence that loganin possesses novel neuroprotective effects.

Platinum complexes featuring pyridine bis-N-heterocyclic-imidazol-2-ylidene/-mesoionic-triazol-5-ylidene donors as pincer ligands and chloro (-Cl), acetonitrile (-NCCH3) or cyano (-CN) groups as auxiliary ligands are prepared as highly strained organometallic phosphors. X-ray structures of four of these complexes confirm a distorted square planar geometry, where the pincer ligand and its mesityl wingtips occur in a twisted conformation to each other. Electrochemical and photophysical characterization have been carried out and the experimental results are interpreted with the aid of density functional theory calculations. Emission responses of complexes under exposure to different vapors and mechanical shear are reported. Notably, the platinum complex featuring pyridine bis-imidazol-2-ylidene and a weakly donating acetonitrile auxiliary ligand exhibited strong aquachromic and mechanochromic emission responses, showing color changes from sky blue to green or yellow-green.

Regional differences in performance in mathematics across Canada prompted us to conduct a comparative study of middle-school mathematics pedagogy in four regions. We built on the work of Tobin, using a theoretical framework derived from the work of Maturana. In this paper, we describe the use of video as part of the methodology used. We used videos of teaching activities as prompts for discussions among teachers and the video recordings of such discussions became the data sources for our comparative research. Our use of video revealed a number of advantages and disadvantages which influenced the research.

Homoleptic ruthenium complexes [Ru(Ln)2]2+ bearing unsymmetric pyridine-based bis N-heterocyclic carbene (NHC) pincer ligands are synthesized and structurally characterized. These complexes feature the coexistence of a five-membered and a six-membered ruthenacycle within the same ligand framework, allowing an ideally octahedral CNHC–Ru–NPy bite angle close to 90°. In the solid state, impressive 3MLCT lifetimes of microsecond regime were detected in all of the complexes, of which [Ru(L4)2]2+, featuring four benzimidazol-2-ylidene donors, exhibited the longest values. Electronic properties of all of the ruthenium complexes are investigated by cyclic voltammetry and spectroscopic techniques. Density functional theory results were used to support the experimental observations.

Ru(II) complexes with two chelating di-N-heterocyclic carbenes (NHC) and two acetonitrile ligands (NHC = 1,1′-dialkyl-3,3′-methylene-diimidazol-2,2′-diylidene, and alkyl = methyl and n-butyl) were synthesized and structurally characterized. The crystal structures of the complexes determined by X-ray diffraction analyses show that the Ru(II) center is bound to two bidentate carbene ligands and two acetonitrile molecules, forming a distorted octahedron. The complexes prove to be an efficient catalyst having exceedingly high turnover frequencies and good reusability in transfer hydrogenation of ketones.

[Hg(La)2](PF6)2 (1), [Hg(Lb)2](PF6)2 (2), [Hg(Lc)2](PF6)2 (3), [Ag(La)2]I (4) and Au(La)Cl (5) (La, Lb, and Lc are aniline or pyridine N-functionalized imidazol-2-ylidene) have been synthesized and characterized. Single crystals of 1·MeOH, 3 and 5 are obtained and their crystal structures are determined by X-ray diffraction analysis. The molecular structure of 1·MeOH shows that Hg(II) center is coordinated to two carbene ligands, one nitrogen atom from aniline group and one oxygen atom from methanol. The anions are embedded between two cations layers and linked the cations through the intermolecular hydrogen bonding. The Hg(II) center of 3 is coordinated to two carbene ligands and two nitrogen atoms from pyridine group. The PF6− anions of 3 hold two adjacent cations through Hg⋯F interactions and H⋯F hydrogen bonding and the crystal packing consists of alternating anion and cation layers. The Au atom of 5 is linearly coordinated with a carbenoic carbon and a chloro ligand, and the molecules are neatly arranged to a one-dimensional hole through weak hydrogen bonding interactions. For 1·MeOH and 5, the –NH2 group of aniline plays an important role in stabilizing the crystal structure through intramolecular and intermolecular hydrogen bonding interactions.

Homoleptic Pd(II) complexes with one and two chelating di-N-heterocyclic carbene (NHC) ligands tagged with pyridinium cation, [Pd2(PyBuCCme)2Cl2](PF6)6 and [Pd (PyBuCCme)2](PF6)6 (PyBuCCme = 1,1′-di-N-(2-pyridinium)butyl-3,3′-methylenediimidazol-2,2′-diylidene), were synthesized and their square planar molecular geometry were determined by X-ray diffraction analysis. These complexes exhibited high catalytic activity toward Heck reaction in both DMF and water.

Group B Streptococcus (GBS) is an important cause of invasive infections in humans. The pathogen encodes a number of virulence factors including the pluripotent beta-haemolysin/cytolysin (beta-H/C). As GBS has the disposition of both a commensal organism and an invasive pathogen, it is important for the organism to appropriately regulate beta-H/C and other virulence factors in response to the environment. GBS can repress transcription of beta-H/C using the two-component system, CovR/CovS. Recently, we described that the serine/threonine kinase Stk1 can phosphorylate CovR at threonine 65 to relieve repression of beta-H/C. In this study, we show that infection with CovR-deficient GBS strains resulted in increased sepsis. Although CovR-deficient GBS showed decreased ability to invade the brain endothelium in vitro, they were more proficient in induction of permeability and pro-inflammatory signalling pathways in brain endothelium and penetration of the blood-brain barrier (BBB) in vivo. Microarray analysis revealed that CovR positively regulates its own expression and regulates the expression of 153 genes. Collectively, our results suggest that the positive feedback loop which regulates CovR transcription modulates host cell interaction and immune defence and may facilitate the transition of GBS from a commensal organism to a virulent meningeal pathogen.

All living organisms respond to changes in their internal and external environment for their survival and existence. Signaling is primarily achieved through reversible phosphorylation of proteins in both prokaryotes and eukaryotes. A change in the phosphorylation state of a protein alters its function to enable the control of cellular responses. A number of serine/threonine kinases regulate the cellular responses of eukaryotes. Although common in eukaryotes, serine/threonine kinases have only recently been identified in prokaryotes. We have described that the human pathogen Group B Streptococcus (GBS, Streptococcus agalactiae) encodes a single membrane-associated, serine/threonine kinase (Stk1) that is important for virulence of this bacterium. In this study, we used a combination of phosphopeptide enrichment and mass spectrometry to enrich and identify serine (S) and threonine (T) phosphopeptides of GBS. A comparison of S/T phosphopeptides identified from the Stk1 expressing strains to the isogenic stk1 mutant indicates that 10 proteins are potential substrates of the GBS Stk1 enzyme. Some of these proteins are phosphorylated by Stk1 in vitro and a site-directed substitution of the phosphorylated threonine to an alanine abolished phosphorylation of an Stk1 substrate. Collectively, these studies provide a novel approach to identify serine/threonine kinase substrates for insight into their signaling in human pathogens like GBS.

International audience; This paper describes some characteristics of the pedagogy informing the teaching of anglophone teachers in Québec, on the basis of focus group interviews conducted as part of a Canada-wide comparative study. The paper also illustrates research methods embedded in an enactivist methodology that permit researchers to take advantage of the observer dependence of interpretations to gain insight into phenomena, like pedagogies, that are not directly observable. The dependence of results on methods used is illustrated in the case of the anglophone Québec focus group.

IGF-binding protein (IGFBP)-3 has intrinsic antiproliferative and proapoptotic functions that are independent of IGF binding and may involve nuclear localization. We determined that exogenous IGFBP-3 rapidly translocates to myoblast nuclei and that a 22-residue peptide containing the metal binding domain (MBD) and nuclear localization sequence (NLS) can similarly direct chimeric GFP into myoblast nuclei. Furthermore, a non-IGF-binding IGFBP-3 mutant inhibited myoblast proliferation without stimulating apoptosis. These results suggest that IGFBP-3 inhibits muscle cell growth in an IGF-independent manner that may be influenced by its rapid nuclear localization. We therefore identified IGFBP-3 interacting proteins by screening a rat L6 myoblast cDNA library using the yeast two-hybrid assay and two N-terminal deletion mutants as bait: BP3/231 (231 residues, L61 to K291) and BP3/111 (K181-K291). Proteins previously known to interact with IGFBP-3 as well as several novel proteins were identified, including RNA polymerase II binding subunit 3 (Rpb3). The domain necessary for Rpb3 binding was subsequently identified using different IGFBP-3 deletion mutants and was localized to the MBD/NLS epitope. Rpb3/IGFBP-3 binding was confirmed by coimmunoprecipitation assays with specific antisera, whereas a NLS mutant IGFBP-3 did not associate with Rpb3, suggesting that a functional NLS is required. Rpb3 facilitates recruitment of the polymerase complex to specific transcription factors and is necessary for the transactivation of many genes. Its association with IGFBP-3 provides a functional role for IGFBP-3 in the direct modulation of gene transcription.

Businesses and people often organize their information of interest (IOI) into a hierarchy of folders (or categories). The personalized folder hierarchy provides a natural way for each of the users to manage and utilize his/her IOI (a folder corresponds to an interest type). Since the interest is relatively long-term, continuous web scanning is essential. It should be directed by precise and comprehensible specifications of the interest. A precise specification may direct the scanner to those spaces that deserve scanning, while a specification comprehensible to the user may facilitate manual refinement, and a specification comprehensible to information providers (e.g. Internet search engines) may facilitate the identification of proper seed sites to start scanning. However, expressing such specifications is quite difficult (and even implausible) for the user, since each interest type is often implicitly and collectively defined by the content (i.e. documents) of the corresponding folder, which may even evolve over time. In this paper, we present an incremental text mining technique to efficiently identify the user's current interest by mining the user's information folders. The specification mined for each interest type specifies the context of the interest type in conjunctive normal form, which is comprehensible to general users and information providers. The specification is also shown to be more precise in directing the scanner to those sites that are more likely to provide IOI. The user may thus maintain his/her folders and then constantly get IOI, without paying much attention to the difficult tasks of interest specification and seed identification.

Document filtering (DF) and document classification (DC) are often integrated together to classify suitable documents into suitable categories. A popular way to achieve integrated DF and DC is to associate each category with a threshold. A document d may be classified into a category c only if its degree of acceptance (DOA) with respect to c is higher than the threshold of c. Therefore, tuning a proper threshold for each category is essential. A threshold that is too high (low) may mislead the classifier to reject (accept) too many documents. Unfortunately, thresholding is often based on the classifier's DOA estimations, which cannot always be reliable, due to two common phenomena: (1) the DOA estimations made by the classifier cannot always be correct, and (2) not all documents may be classified without any controversy. Unreliable estimations are actually noises that may mislead the thresholding process. In this paper, we present an adaptive and parameter-free technique AS4T to sample reliable DOA estimations for thresholding. AS4T operates by adapting to the classifier's status, without needing to define any parameters. Experimental results show that, by helping to derive more proper thresholds, AS4T may guide various classifiers to achieve significantly better and more stable performances under different circumstances. The contributions are of practical significance for real-world integrated DF and DC.

To facilitate searching and navigation, much information has been hierarchically organized into categories with different levels of generality. However, users still suffer information overload in querying a hierarchical information space, since they often cannot make their aspects of interest precise enough. One way to alleviate the problem is to interactively identify those information categories that correspond to the users' information needs (INs). In that case, information of interest may be found in a more dedicated space (i.e. subset of categories), promoting both search precision and user satisfaction. This paper presents a technique that employs text mining to build each category's profile through which users' INs may be interactively identified. The profiles are mined incrementally so that the system may adapt to the ever-changing information space. The technique is shown to be effective in mapping users' INs to suitable categories without requiring the users to enter long queries, conduct many interactions, and suffer heavy cognitive load. It may serve as an intelligent intermediary in various applications that link users to suitable information categories and service departments.

Traditionally, Canadian Inuit have lived in the circumpolar regions of Canada and those who still live in these regions, have their own cultures, which they tend to celebrate in their educational curricula. Inuit culture reflects their traditional lifestyle, when they were nomadic, and hunted and fished to survive in incredibly difficult conditions. These cultural differences present many challenges and issues to some mathematical concepts; for instance, for Nunavik Inuit, the concept of probability has no formal definition and it does not take the same meaning as in conventional mathematics. This misalignment could cause negative effects on students’ learning. Looking to bridge the gap between those two different cultural meanings, the principal investigator, Annie Savard, with the assistance of Inuit educators designed learning situations based on the traditional Inuit culture. We used an ethnomathematical model (Savard, 2008b) to frame the learning situations created. In this article, we present the learning situations created that aimed to bridge Nunavik Inuit culture and the development of probabilistic reasoning and we discuss how these learning situations supported students’ mathematical understanding and cultural identity.Keywords: Nunavik Inuit traditional culture; probability; learning situationethnomathematical model

N-Pyridyl, N'-amido functionalized imidazolium bromides were obtained in high yields as an N-heterocyclic carbene (NHC) precursor and used as bidentate or a pincer ligands to obtain ruthenium complexes via a silver NHC transmetallation route. The incorporation of a phenyl group as an amido-N substituent (R = Ph) results in a bidentate coordination mode through the C(NHC) and N(pyridyl) donors, whereas in its absence (R = H) a pincer coordination mode was observed through the N(pyridyl)^C(NHC)^O(amido) donors. The ruthenium complex featuring a pincer type NCO coordination mode with a protic NH function adjacent to the coordinating O(amido) atom was found to efficiently catalyse the oxidation of activated alcohols effecting quantitative conversions within 30 minutes. However the oxidation of deactivated alcohols required longer reaction times to effect the quantitative transformation.

Our previous study showed that mossy fiber sprouting can occur in the hippocampus region in rats 6 wk after kainic acid-induced epileptic seizure, and this mossy fiber sprouting can facilitate epileptogenesis. Transcutaneous auricular vagal nerve stimulation (VNS), which is similar to cervical VNS, can reduce the occurrence of epileptic seizure in intractable epilepsy patients. Greater parasympathetic nerve activity can be caused by 2 Hz electroacupuncture (EA). Therefore, we investigated the effect of 2 Hz EA at ST-36-ST37 and at the ear on mossy fiber sprouting in kainic-treated Sprague-Dawley rats. The results indicated that applying 2 Hz EA at ST36-ST37 and at the ear for 3 d per week over 6 consecutive weeks can ameliorate mossy fiber sprouting in the hippocampus region of rats. These results indicated that applying 2 Hz EA at ST36-ST37 and at the ear might be beneficial for the treatment and prevention of epilepsy in humans.

A new series of ruthenium(II) carbonyl complexes with benzene-based CCC-pincer bis-(carbene) ligands, [((R)CCC(R))Ru(CO)2(X)](0/+) and [((R)CCC(R))Ru(CO)(NN)](+) ((R)CCC(R) = 2,6-bis-(1-alkylimidazolylidene)benzene, R = Me or (n)Bu; X = I, Br, CH3CN, or 6-(aminomethyl)pyridine (ampy); NN = 2·CH3CN, or chelating ampy or bipyridine), was synthesized and fully characterized. X-Ray structure determinations revealed that these eight complexes have pseudo-octahedral configurations around the ruthenium center with the pincer ligand occupying three meridional sites. These complexes prove to be efficient precatalysts demonstrating very good activity and reusability for the transfer hydrogenation of ketones.

Secure localization has gained considerable attention because position estimation is often required for location based applications. This problem becomes more important for wireless local area networks (WLANs), where the radio signals are susceptible to a variety of attacks due to the nature of the open medium. This paper proposes a survey of security positioning systems in WLANs. We classify secure positioning mechanisms into two categories: signal-based and model-based approaches. The former attempts to detect attacks and exclude them during positioning while the latter enhances localization schemes capable of tolerating attacks. This study examines three signal-based approaches, including median-based method, sensor selection, and RSM (Ration-based Signal strength Metric), and three model-based approaches, including cluster-based method, RWGH (Residual Weighting), and IDM (Inclusive Disjunction Model). We evaluate their robustness to attacks, positioning accuracy, and computational complexity. Simulation results show that the model-based techniques generally perform better robustness; However, the improvement is gained at the expense of degrading performance in an attack-free condition and higher computational overhead. This paper also investigates how the number of attacks impact these secure positioning algorithms.

A novel palladium complex with chelating NHC ligand is prepared and efficiently applied as a reusable catalyst for the Heck reaction.

This pilot study sought to examine the mathematical knowledge for teaching that pre-service teachers used when participating in an online community, and to gain insight into their epistemological stance. The participants of this study were among the pre-service teachers in a large urban university, chosen as they were completing their mathematics methods course in their teacher-education program and before entering a field experience in the same academic year. A qualitative analysis of the online discussions of our participants was done using Ball and her colleagues’ (2008) framework for mathematical knowledge for teaching and that of communities of practice (Wenger, 1998). These theories provided insight into the development of pre-service teachers as they moved from “student” to “teacher”. Our findings show that pre-service teachers struggle to shed their student-perspective as they transition from theory to practice. This was readily evident in how they used their mathematical knowledge for teaching in their online exchange. Our work contributes to understanding the complexity of becoming a mathematics teacher in elementary school.

As making concession is the essential action for reducing the gap between the involved negotiators, the purpose of this study explored the concession triggering factors and their relative influence from both dyadic and interaction-based perspectives based on complete e-negotiation transcripts including the exchanged messages and offers. We found the negotiator's own last offer is the most powerful concession triggering factor and the counterpart's concession is the next one. Further, the integrative information exchange has positive impact, while the distributive information exchange has negative impact. Another significant impact factor is the procedural communication. However, the impact of negotiation time progress was not significant.

Exotoxins, including the hemolysins known as the alpha (alpha) and beta (beta) toxins, play an important role in the pathogenesis of Staphylococcus aureus infections. A random transposon library was screened for S. aureus mutants exhibiting altered hemolysin expression compared to wild type. Transposon insertions in 72 genes resulting in increased or decreased hemolysin expression were identified. Mutations inactivating a putative cyclic di-GMP synthetase and a serine/threonine phosphatase (Stp1) were found to reduce hemolysin expression, and mutations in genes encoding a two component regulator PhoR, LysR family transcriptional regulator, purine biosynthetic enzymes and a serine/threonine kinase (Stk1) increased expression. Transcription of the hla gene encoding alpha toxin was decreased in a Deltastp1 mutant strain and increased in a Deltastk1 strain. Microarray analysis of a Deltastk1 mutant revealed increased transcription of additional exotoxins. A Deltastp1 strain is severely attenuated for virulence in mice and elicits less inflammation and IL-6 production than the Deltastk1 strain. In vivo phosphopeptide enrichment and mass spectrometric analysis revealed that threonine phosphorylated peptides corresponding to Stk1, DNA binding histone like protein (HU), serine-aspartate rich fibrinogen/bone sialoprotein binding protein (SdrE) and a hypothetical protein (NWMN_1123) were present in the wild type and not in the Deltastk1 mutant. Collectively, these studies suggest that Stk1 mediated phosphorylation of HU, SrdE and NWMN_1123 affects S. aureus gene expression and virulence.

Gender issues have been present in the traditional negotiation field for a long time, as it has become common for women to play key roles in business. However, few studies have investigated this issue in online situations. Since online negotiation is inevitable in the global business age and its context is different from that of a traditional face-to-face environment, it is valuable to have more understanding of the impact of gender differences on online negotiation. This study explores the impact of different gender dyads on how negotiators strategically respond to their counterparts’ behavior from the dyadic interaction perspective. The adopted strategy clusters include (1) distributive information, (2) integrative information, (3) claiming value, and (4) creating value. The content analysis method was applied in order to translate all negotiation transcripts into quantitative data, i.e. behavior units. The resulting behavior units belonging to the four strategy clusters were mined to find the two-sequence dyadic behavioral patterns of each negotiation dyad and then of each gender composition group. Finally, these two-sequence behavioral patterns were categorized into three appropriate strategic behavioral sequences: (1) reciprocal sequence, (2) complementary sequence, and (3) structural sequence. The results indicate that negotiators’ strategic responses to their counterparts were impacted by the genders of both the counterparts and the negotiators themselves. In general, negotiators in intra-gender dyads adopt more structural strategy and less reciprocal strategy than those in inter-gender dyads. No matter whether female or male, a negotiator will adapt his or her response strategy based on his or her counterpart’s gender.

All living organisms communicate with the external environment for their survival and existence. In prokaryotes, communication is achieved by two-component systems (TCS) comprising histidine kinases and response regulators. In eukaryotes, signalling is accomplished by serine/threonine and tyrosine kinases. Although TCS and serine/threonine kinases coexist in prokaryotes, direct cross-talk between these families was first described in Group B Streptococcus (GBS). A serine/threonine kinase (Stk1) and a TCS (CovR/CovS) co-regulate toxin expression in GBS. Typically, promoter binding of regulators like CovR is controlled by phosphorylation of the conserved active site aspartate (D53). In this study, we show that Stk1 phosphorylates CovR at threonine 65. The functional consequence of threonine phosphorylation of CovR in GBS was evaluated using phosphomimetic and silencing substitutions. GBS encoding the phosphomimetic T65E allele are deficient for CovR regulation unlike strains encoding the non-phosphorylated T65A allele. Further, compared with wild-type or T65A CovR, the T65E CovR is unable to bind promoter DNA and is decreased for phosphorylation at D53, similar to Stk1-phosphorylated CovR. Collectively, we provide evidence for a novel mechanism of response regulator control that enables GBS (and possibly other prokaryotes) to fine-tune gene expression for environmental adaptation.

This study explored the influence of language familiarity on persuasion behavior in e-negotiation. This was motivated by booming global e-business and the resulting popularity of cross-country e-negotiation. A laboratory e-negotiation experiment was conducted with two groups who used native and nonnative language in negotiation separately. We found that language familiarity has a positive effect on both language self-efficacy and negotiation self-efficacy. Moreover, mediated effect analyses revealed a critical effect path from language self-efficacy to negotiation self-efficacy to communication efficiency to communication effectiveness to persuasion behavior. This indicates that language familiarity is the fundamentally critical factor in guiding persuasion behavior since it can affect both language self-efficacy and negotiation self-efficacy. Therefore, determining how to improve both language self-efficacy and negotiation self-efficacy when negotiating in a nonnative language is very important. Finally, possible contributions provided by information technology are proposed from the viewpoint of the information systems discipline.

Ever since the boom in global e-business, and the resulting intensification of competition, cross-cultural e-negotiation has increased in popularity. Understanding how national cultures affect negotiation behaviour is becoming more and more critical for businesses. This research will explore how a negotiator's cultural background impacts its behaviour. There are four major findings: firstly, that Eastern and Western businesses have unique negotiation behaviours; secondly, that the negotiation behaviours of both Eastern and Western negotiators are impacted by their counterparts' cultural background; thirdly, that when Easterners negotiate with Westerners, there were more instances of task behaviour and persuasive behaviour, but fewer instances of procedural behaviour and private communication; and finally, that when Westerner negotiates with Easterner, there are more instances of task behaviour but fewer of private communication. In spite of the similarities, however, Western negotiators have more consistent negotiation behaviour than do their Eastern equivalents, regardless of cultural differences between the dyadic negotiators. The following research uses the content analysis method, which is more thorough than the questionnaire in terms of qualitative criteria. The total set of thought units can be analyzed from further viewpoints in the future.

Here we demonstrate an efficient method to fabricate large-domain monodisperse foam scaffolds made of gelatin for 3D cell culture. We tested three distinct tissue cell types cultured in foam scaffolds composed of uniform spherical pores. The cells displayed appropriate morphological and physiological characteristics: epithelial cells formed cyst-like structures and were polarized inside pores, myoblasts adopted a tubular structure and fused into myotubes, and fibroblasts exhibited a wide variety of morphologies. Scaffolds with uniform pores can thus provide a platform for systematic study of 3D cell–matrix interactions.

We create a novel 3D matrix with uniform and ordered pores by microfluidic technique. We can vary the pore size and the interconnection between the pores andmeasure the elastic modulus of the matrix. We culture cells inside and observe their morphology by confocal microscopy. Our matrix allows 3D cell cultures in a uniform environment.View Large Image | View Hi-Res Image | Download PowerPoint Slide

We have created 3D ordered gelatin scaffolds with monodisperse pores and cultured 3T3 fibroblasts inside. We are interested to explore the effect of microenvironment on the cell morphologies. The morphologies of cells are observed through labeling the F-actin inside the cells with fluorescent phalloidin and imaged by a confocal microscope. We compare the cell morphologies in the following microenvironment - on a 2D hard surface, on a 2D soft gelatin surface, in a 3D collagen gel, and scaffolds of different pore sizes. We found that the cells exhibit wide range of morphologies in different microenvironment. We classified cell shapes into three categories and measured the extension of cells by fitting with an ellipsoid. From the trend of cell extensions, a cell in a large pore resembles one on 2D soft gel surface. This result suggests a crossover in length from 2D-like to 3D-like morphology for cell cultured on a curved surface.View Large Image | View Hi-Res Image | Download PowerPoint Slide