Dating Business Cycles in a Historical Perspective: Evidence for Switzerland

In this study we suggest a chronology of the classical business cycle in Switzerland. To this end we use two approaches: the approach of Artis et al. (2004) and an approach based on Markov-switching models (Hamilton, 1989). Our results show that similar conclusions can be reached by applying the two methodologies. Another result is that the chronology obtained displays high concordance with the chronology derived for the Euro Area by the CEPR Business Cycle Dating Committee. A further contribution of our study is that we determine the sensitivity of the chronology obtained with respect to a particular GDP vintage used. For this purpose we employ the real-time database that contains 53 vintages of GDP data starting from 1997Q4 until 2010Q4. The main result of this robustness exercise is that the chronology obtained is stable across different vintages, although some minor differences across vintages can be detected

"Nanohybrids" based on pH-responsive hydrogels and inorganic nanoparticles for drug delivery and sensor applications.

Allyl-PEG capped inorganic NPs, including magnetic iron oxide (IONPs), fluorescent CdSe/ZnS quantum dots (QDs), and metallic gold (AuNPs of 5 and 10 nm) both individually and in combination, were covalently attached to pH-responsive poly(2-vinylpyridine-co-divinylbenzene) nanogels via a facile and robust one-step surfactant-free emulsion polymerization procedure. Control of the NPs associated to the nanogels was achieved by the late injection of the NPs to the polymerization solution at a stage when just polymeric radicals were present. Remarkably, by varying the total amount of NPs injected, the swelling behavior could be affected. Furthermore, the magnetic response as well as the optical features of the nanogels containing either IONPs or QDs could be modified. In addition, a radical quenching in case of gold nanoparticles was observed, thus affecting the final nanogel geometry

Effects of Aging and Cyclosporin A on Collagen Turnover in Human Gingiva

BACKGROUND: WE AIMED AT CHARACTERIZING THE AGING GINGIVA ANALYZING: i) collagen content and turnover in human gingival tissues and fibroblasts obtained from healthy young and aging subjects. ii) the effect of cyclosporin A administration in human cultured gingival fibroblasts obtained from aging compared to young subjects. METHODS: Morphological analysis was performed on haematoxylin-eosin and Sirius red stained paraffin-embedded gingival biopsies from young and aging healthy subjects. The expression of the main genes and proteins involved in collagen turnover were determined by real time PCR, dot blot and SDS-zymography on cultured young and aging gingival fibroblasts, and after cyclosporin A administration. RESULTS: Our results suggest that in healthy aged people, gingival connective tissue is characterized by a similar collagen content and turnover. Collagen turnover pathways are similarly affected by cyclosporin A treatment in young and aging gingival fibroblasts. CONCLUSIONS: Cyclosporin A administration affects gingival collagen turnover pathways in young and aging fibroblasts at the same extent, suggesting that during aging cyclosporin A administration is not related to relevant collagen turnover modifications

Lipidoid-Coated Iron Oxide Nanoparticles for Efficient DNA and siRNA delivery

The safe, targeted and effective delivery of gene therapeutics remains a significant barrier to their broad clinical application. Here we develop a magnetic nucleic acid delivery system composed of iron oxide nanoparticles and cationic lipid-like materials termed lipidoids. Coated nanoparticles are capable of delivering DNA and siRNA to cells in culture. The mean hydrodynamic size of these nanoparticles was systematically varied and optimized for delivery. While nanoparticles of different sizes showed similar siRNA delivery efficiency, nanoparticles of 50–100 nm displayed optimal DNA delivery activity. The application of an external magnetic field significantly enhanced the efficiency of nucleic acid delivery, with performance exceeding that of the commercially available lipid-based reagent, Lipofectamine 2000. The iron oxide nanoparticle delivery platform developed here offers the potential for magnetically guided targeting, as well as an opportunity to combine gene therapy with MRI imaging and magnetic hyperthermia.National Heart, Lung, and Blood InstituteNational Institutes of Health (U.S.) (Program of Excellence in Nanotechnology (PEN) Award, Contract #HHSN268201000045C

Characterization of a Human Cell Line Stably Over-Expressing the Candidate Oncogene, Dual Specificity Phosphatase 12

Analysis of chromosomal rearrangements within primary tumors has been influential in the identification of novel oncogenes. Identification of the "driver" gene(s) within cancer-derived amplicons is, however, hampered by the fact that most amplicons contain many gene products. Amplification of 1q21-1q23 is strongly associated with liposarcomas and microarray-based comparative genomic hybridization narrowed down the likely candidate oncogenes to two: the activating transcription factor 6 (atf6) and the dual specificity phosphatase 12 (dusp12). While atf6 is an established transcriptional regulator of the unfolded protein response, the potential role of dusp12 in cancer remains uncharacterized.To evaluate the oncogenic potential of dusp12, we established stable cell lines that ectopically over-express dusp12 in isolation and determined whether this cell line acquired properties frequently associated with transformed cells. Here, we demonstrate that cells over-expressing dusp12 display increased cell motility and resistance to apoptosis. Additionally, over-expression of dusp12 promoted increased expression of the c-met proto-oncogene and the collagen and laminin receptor intergrin alpha 1 (itga1) which is implicated in metastasis.Collectively, these results suggest that dusp12 is oncologically relevant and exposes a potential association between dusp12 and established oncogenes that could be therapeutically targeted

Photocatalytic Nanolithography of Self-Assembled Monolayers and Proteins

Self-assembled monolayers of alkylthiolates on gold and alkylsilanes on silicon dioxide have been patterned photocatalytically on sub-100 nm length-scales using both apertured near-field and apertureless methods. Apertured lithography was carried out by means of an argon ion laser (364 nm) coupled to cantilever-type near-field probes with a thin film of titania deposited over the aperture. Apertureless lithography was carried out with a helium–cadmium laser (325 nm) to excite titanium-coated, contact-mode atomic force microscope (AFM) probes. This latter approach is readily implementable on any commercial AFM system. Photodegradation occurred in both cases through the localized photocatalytic degradation of the monolayer. For alkanethiols, degradation of one thiol exposed the bare substrate, enabling refunctionalization of the bare gold by a second, contrasting thiol. For alkylsilanes, degradation of the adsorbate molecule provided a facile means for protein patterning. Lines were written in a protein-resistant film formed by the adsorption of oligo(ethylene glycol)-functionalized trichlorosilanes on glass, leading to the formation of sub-100 nm adhesive, aldehyde-functionalized regions. These were derivatized with aminobutylnitrilotriacetic acid, and complexed with Ni2+, enabling the binding of histidine-labeled green fluorescent protein, which yielded bright fluorescence from 70-nm-wide lines that could be imaged clearly in a confocal microscope

Work-life balance in the police: the development of a self-management competency framework

Purpose Addressing a gap in the current work–life balance (WLB) literature regarding individual-focused approaches to inform interventions, we elicited behaviors used to self-manage WLB to draw up a competency-based WLB framework for relevant learnable knowledge, skills, and abilities (KSAs; Hoffmann, Eur J Ind Train 23:275–285, 1999) and mapping this against extant WLB frameworks. Design/Methodology/Approach Our participants were from a major UK police force, which faces particular challenges to the work–life interface through job demands and organizational cutbacks, covering a range of operational job roles, including uniformed officers and civilian staff. We took a mixed methods approach starting with semi-structured interviews to elicit 134 distinct behaviors (n = 20) and used a subsequent card sort task (n = 10) to group these into categories into 12 behavioral themes; and finally undertook an online survey (n = 356) for an initial validation. Findings Item and content analysis reduced the behaviors to 58, which we analyzed further. A framework of eight competencies fits the data best; covering a range of strategies, including Boundary Management, Managing Flexibility, and Managing Expectations. Implications The WLB self-management KSAs elicited consist of a range of solution-focused behaviors and strategies, which could inform future WLB-focused interventions, showing how individuals may negotiate borders effectively in a specific environment. Originality/Value A competence-based approach to WLB self-management is new, and may extend existing frameworks such as Border Theory, highlighting a proactive and solution-focused element of effective behaviors

Magnetic hyperthermia controlled drug release in the GI tract : solving the problem of detection

Drug delivery to the gastrointestinal (GI) tract is highly challenging due to the harsh environments any drug- delivery vehicle must experience before it releases it’s drug payload. Effective targeted drug delivery systems often rely on external stimuli to effect release, therefore knowing the exact location of the capsule and when to apply an external stimulus is paramount. We present a drug delivery system for the GI tract based on coating standard gelatin drug capsules with a model eicosane- superparamagnetic iron oxide nanoparticle composite coating, which is activated using magnetic hyperthermia as an on-demand release mechanism to heat and melt the coating. We also show that the capsules can be readily detected via rapid X-ray computed tomography (CT) and magnetic resonance imaging (MRI), vital for progressing such a system towards clinical applications. This also offers the opportunity to image the dispersion of the drug payload post release. These imaging techniques also influenced capsule content and design and the delivered dosage form. The ability to easily change design demonstrates the versatility of this system, a vital advantage for modern, patient-specific medicine

Magnetic resonance imaging (MRI) contrast agents for tumor diagnosis

10.1260/2040-2295.4.1.23Journal of Healthcare Engineering4123-4

Analysis of Tp53 Codon 72 Polymorphisms, Tp53 Mutations, and HPV Infection in Cutaneous Squamous Cell Carcinomas

Non-melanoma skin cancers are one of the most common human malignancies accounting for 2-3% of tumors in the US and represent a significant health burden. Epidemiology studies have implicated Tp53 mutations triggered by UV exposure, and human papilloma virus (HPV) infection to be significant causes of non-melanoma skin cancer. However, the relationship between Tp53 and cutaneous HPV infection is not well understood in skin cancers. In this study we assessed the association of HPV infection and Tp53 polymorphisms and mutations in lesional specimens with squamous cell carcinomas.We studied 55 cases of histologically confirmed cutaneous squamous cell carcinoma and 41 controls for the presence of HPV infection and Tp53 genotype (mutations and polymorphism).We found an increased number of Tp53 mutations in the squamous cell carcinoma samples compared with perilesional or control samples. There was increased frequency of homozygous Tp53-72R polymorphism in cases with squamous cell carcinomas, while the Tp53-72P allele (Tp53-72R/P and Tp53-72P/P) was more frequent in normal control samples. Carcinoma samples positive for HPV showed a decreased frequency of Tp53 mutations compared to those without HPV infection. In addition, carcinoma samples with a Tp53-72P allele showed an increased incidence of Tp53 mutations in comparison carcinomas samples homozygous for Tp53-72R.These studies suggest there are two separate pathways (HPV infection and Tp53 mutation) leading to cutaneous squamous cell carcinomas stratified by the Tp53 codon-72 polymorphism. The presence of a Tp53-72P allele is protective against cutaneous squamous cell carcinoma, and carcinoma specimens with Tp53-72P are more likely to have Tp53 mutations. In contrast Tp53-72R is a significant risk factor for cutaneous squamous cell carcinoma and is frequently associated with HPV infection instead of Tp53 mutations. Heterozygosity for Tp53-72R/P is protective against squamous cell carcinomas, possibly reflecting a requirement for both HPV infection and Tp53 mutations