A presente pesquisa procura estudar uma mudança organizacional de larga escala em uma rede hoteleira multinacional. Esta mudança tem como foco a implementação de um Centro de Serviços Compartilhados (CSC) que passa a realizar de forma centralizada as rotinas e processos administrativos, contábeis e financeiros de mais de quarenta unidades hoteleiras do grupo. Na implementação de mudanças desta magnitude, é necessário lidar com as resistências internas da organização que se apresentam no decorrer do processo. Neste sentido, esta pesquisa objetiva estudar quais são as principais resistências que envolvem um processo de mudança, tomando como ponto base os elementos da resistência apontados por Burns e Scapens (2000). Este construto foi desenvolvido para dar um foco intraorganizacional aos processos de mudança, sendo influenciado pela Old Institutional Economics (OIE), e procura sanar algumas críticas postas às primeiras pesquisas da New Institutional Sociology (NIS) pelas quais esta última estaria descrevendo os processos de mudança como lineares e inevitáveis, nos quais os atores se tornavam voluntariamente isomórficos às instituições. Com base neste construto, este trabalho procura analisar os elementos de resistência (i) por existência de conflito de interesses; (ii) por falta de competência (conhecimento e / ou experiência); e (iii) por apego às instituições postas no ambiente...
O objetivo deste trabalho foi a preparação de um revestimento inteligente com resina epóxi, capaz de autorreparar-se quando o sofre um defeito mecânico. A autorreparação é possibilitada pela presença de microcápsulas, dispersas na resina (revestimento de epóxi sem pigmentos) e que contêm no seu núcleo o agente de autorreparação, o óleo de linhaça. Estas cápsulas foram preparadas por uma emulsão de óleo de linhaça em água para formar micelas e sobre estas uma parede ou casca exterior de poliuréia-formaldeído. Para a avaliação da resistência à corrosão e do efeito de autorreparação do revestimento, chapas de aço carbono foram revestidas e avaliadas pela técnica de espectroscopia de impedância eletroquímica (EIE) em 0.1molL-1 1 NaCl e também foram avaliadas pelo teste acelerado de corrosão em câmara de névoa salina (SSC). Após a cura do revestimento aditivado com as microcápsulas, aplicado sobre placas de aço carbono, as medidas eletroquímicas de impedância foram realizadas em corpos de prova com um defeito mecânico provocado de forma controlada e reprodutível. Uma célula de três eletrodos foi utilizada. Estas medidas foram efetuadas após 0h, 24h e 48h da execução da incisão ou defeito mecânico. Para comparação...
Em mamíferos, a espermatogênese é mantida pela autorrenovação e diferenciação das células-tronco espermatogoniais (SSC). Apesar da grande importância do SSC para a fertilidade masculina, em Bos taurus pouco se sabe sobre a sua identificação e biologia celular. Para roedores, mais de 30 marcadores para células germinativas indiferenciadas já foram descritos. No entanto, ainda não é conhecido um marcador específico apenas para SSC. Quase todos são também expressos por gonócitos, espermatogônias mais diferenciadas ou mesmo células somáticas. Yin Yang 2 (YY2) é um factor de transcrição expresso nas células com a morfologia de gonócitos e SSC, sendo um candidato a marcador de SSC. Assim, a identificação de novos marcadores para SSC e factores que afectam a sua expressão, tais como a idade, são fundamentais para o desenvolvimento da biotecnologia como transgenia e tratamento de infertilidade, nos quais as SSC poderiam ser ferramentas biológicos importantes. Assim, nesta tese temos duas hipóteses principais: 1) a idade do dador afeta a expressão de marcadores moleculares específicos de SSC bovinas assim como potencial de células-tronco dessas células e que as sequências de DNA em que se associa YY2 regulam a expressão génica de SSC em camundongos. Os objetivos específicos...
We have previously identified the gene (the ssc gene) defective in the thermosensitive and antibiotic-supersusceptible outer membrane permeability mutant SS-C of Salmonella typhimurium and shown that this gene is analogous to the Escherichia coli gene firA (L. Hirvas, P. Koski, and M. Vaara, EMBO J. 10:1017-1023, 1991). Others have tentatively implicated firA in a different function, mRNA synthesis. Here we report that the defect in the thermosensitive outer membrane omsA mutant of E. coli (T. Tsuruoka, M. Ito, S. Tomioka, A. Hirata, and M. Matsuhashi, J. Bacteriol. 170:5229-5235, 1988) is due to a mutation in firA; this mutation changed codon 271 from serine to asparagine. The omsA-induced phenotype was completely reverted by plasmids containing wild-type firA or ssc. Plasmids carrying the omsA allele, or an identical mutant allele prepared by localized mutagenesis, under the control of lac elicited partial complementation. Transcomplementation studies with plasmids carrying various mutant alleles of the S. typhimurium gene indicated that the ability of these plasmids to complement the omsA mutation was similar to their ability to complement the ssc mutation. The antibiotic-supersusceptible phenotype of the omsA mutant closely resembled that of the ssc mutant...
To determine the prevalence and the characterization of antibodies to endothelial cells in patients with SSc, serum samples from 80 patients with SSc, 20 patients with systemic lupus erythematosus (SLE), and 20 healthy control subjects were examined by ELISA using cultured human umbilical vein endothelial cells (HUVEC), indirect immunofluorescence analysis (IIF), and immunoblotting using cytoplasmic extract of HUVEC. IgG and/or IgM isotype anti-endothelial cell antibodies (AECA) were demonstrated by ELISA in 43 of 80 patients with SSc (54%), in 15 of 20 patients with SLE (75%), and in none of 20 healthy control subjects. Immunofluorescence analysis on HUVEC substrate showed homogeneous cytoplasmic staining. Immunoblotting demonstrated that these patients had antibodies directed to one or several antigens of approximately 60, 90, 110 and 140 kD, and the most common responses were to the 90-kD antigen. By the immunofluorescence method using HUVEC, affinity-purified anti-90-kD antibodies showed identical cytoplasmic staining to that produced by sera positive for AECA. Furthermore, AECA were closely correlated with pulmonary fibrosis in patients with SSc. These findings suggest that patients with SSc have abnormal antibodies to endothelial cell antigens...
Peripheral microvascular impairment in systemic sclerosis (SSc) may be
easily detected and scored in a safe noninvasive way by nailfold
videocapillaroscopy (NVC). The paper highlights clinical conditions related to SSc in which NVC may represent an outcome measure of therapeutical interventions, by elaborating
on their already assessed relationship with the NVC patterns and eventually
scores. The 3 important biological/clinical conditions are: the positivity for
SSc-specific serum autoantibodies, the presence of SSc skin digital ulcers
(DUs) and of pulmonary arterial hypertension (PAH) SSc associated.
In conclusion, to the question if capillaroscopy (NVC) may represent in SSc
an outcome measure for clinical trials on the peripheral vasculopathy, based
on the growing evidence and our detailed studies, the answer is positive.
Recent therapeutic trials in SSc are confirming this role, and the experience is
Spermatogonia stem cell (SSC) self-renewal and differentiation are tightly regulated processes that ensure a continued production of mature sperm throughout male adulthood. In the present study, we investigated the role of glucocorticoid-induced leucine zipper (GILZ) in maintenance of the male germline and spermatogenesis. GILZ was detectable in germ cells of wild type mice on the day of birth, suggesting a role for GILZ in prospermatogonia and SSC pool formation. Gilz KO mice were generated and adult males were azoospermic and sterile. During the first wave of spermatogenesis in Gilz KO mice, spermatogenesis arrested part way through pachytene of meiosis I. Subsequent waves resulted in a progressive depletion of germ cells through apoptosis to ultimately produce a Sertoli cell-only phenotype. Further, in contrast to wild type littermates, PLZF+ cells were detected in the peri-luminal region of Gilz KO mice at day 6 post-natal, suggesting a defect in prospermatogonia migration in the absence of GILZ. At age 30 days, transient accumulation of PLZF+ cells in a subset of tubules and severely compromised spermatogenesis were observed in Gilz KO mice, consistent with defective SSC differentiation. GILZ deficiency was associated with an increase in FOXO1 transcriptional activity...
Systemic sclerosis (SSc) is a chronic disease, with early activation of the immune system. The aim of our work was to address how SSc–mesenchymal stem cells (MSCs), although senescent, might preserve specific immunomodulatory abilities during SSc. MSCs were obtained from 10 SSc patients and 10 healthy controls (HC). Senescence was evaluated by assessing cell cycle, β-galactosidase (β-Gal) activity, p21 and p53 expression; doxorubicin was used as acute senescence stimulus to evaluate their ability to react in stressed conditions. Immunomodulatory abilities were studied co-culturing MSCs with peripheral blood mononuclear cells (PBMCs) and CD4+ cells, in order to establish both their ability to block proliferation in mixed lymphocyte reaction and in regulatory T cells (Tregs) induction. SSc–MSC showed an increase of senescence biomarkers. Eighty per cent of MSCs were in G0–G1 phase, without significant differences between SSc and HC. SSc–MSCs showed an increased positive β-Gal staining and higher p21 transcript level compared to HC cells. After doxorubicin, β-Gal staining increased significantly in SSc–MSCs. On the contrary, doxorubicin abolished p21 activation and elicited p53 induction both in SSc– and HC–MSCs. Interleukin (IL)-6 and transforming growth factor (TGF)-β-related transcripts and their protein levels were significantly higher in SSc–MSCs. The latter maintained their immunosuppressive effect on lymphocyte proliferation and induced a functionally regulatory phenotype on T cells...
Systemic sclerosis (SSc) is a multisystem autoimmune disease of unknown etiology characterized by inflammation, autoantibody production, and fibrosis. It predominantly affects women, this suggesting that female sex hormones such as estrogens may play a role in disease pathogenesis. However, up to date, the role of estrogens in SSc has been scarcely explored. The activity of estrogens is mediated either by transcription activity of the intracellular estrogen receptors (ER), ERα and ERβ, or by membrane-associated ER. Since the presence of autoantibodies to ERα and their role as estrogen agonists interfering with T lymphocyte homeostasis were demonstrated in other autoimmune diseases, we wanted to ascertain whether anti-ERα antibodies were detectable in sera from patients with SSc. We detected anti-ERα antibody serum immunoreactivity in 42% of patients with SSc (30 out of 71 analyzed). Importantly, a significant association was found between anti-ERα antibody values and key clinical parameters of disease activity and severity. Fittingly, anti-ERα antibody levels were also significantly associated with alterations of immunological features of SSc patients, including increased T cell apoptotic susceptibility and changes in T regulatory cells (Treg) homeostasis. In particular...
Previous studies have shown that the transforming growth factor (TGF)β/Alk1/Smad1 signaling pathway is constitutively activated in a subset of systemic sclerosis (SSc) fibroblasts and this pathway is a critical regulator of CCN2 gene expression. Caveolin-1 (cav-1), an integral membrane protein and the main component of caveolae, has also been implicated in SSc pathogenesis. This study was undertaken to evaluate the role of caveolin-1 in Smad1 signaling and CCN2 expression in healthy and SSc dermal fibroblasts. We show that a significant subset of SSc dermal fibroblasts has up-regulated cav-1 expression in vitro, and that cav-1 up-regulation correlates with constitutive Smad1 phosphorylation. In addition, basal levels of phospho-Smad1 were down-regulated after inhibition of cav-1 in SSc dermal fibroblasts. Caveolin-1 formed a protein complex with Alk1 in dermal fibroblasts, and this association was enhanced by TGFβ. By using siRNA against cav-1 and adenoviral cav-1 overexpression we demonstrate that activation of Smad1 in response to TGFβ requires cav-1 and that cav-1 is sufficient for Smad-1 phosphorylation. We also show that cav-1 is a positive regulator of CCN2 gene expression, and that it is required for the basal and TGFβ-induced CCN2 levels. In conclusion...
Fonte: Public Library of SciencePublicador: Public Library of Science
Tipo: Artigo de Revista Científica
Relevância na Pesquisa
Introduction: Human leukocyte antigen (HLA) polymorphism studies in Systemic Sclerosis (SSc) have yielded variable results. These studies need to consider the genetic admixture of the studied population. Here we used our previously reported definition of genetic admixture of Mexicans using HLA class I and II DNA blocks to map genetic susceptibility to develop SSc and its complications. Methods: We included 159 patients from a cohort of Mexican Mestizo SSc patients. We performed clinical evaluation, obtained SSc-associated antibodies, and determined HLA class I and class II alleles using sequence-based, high-resolution techniques to evaluate the contribution of these genes to SSc susceptibility, their correlation with the clinical and autoantibody profile and the prevalence of Amerindian, Caucasian and African alleles, blocks and haplotypes in this population. Results: Our study revealed that class I block HLA-C*12:03-B*18:01 was important to map susceptibility to diffuse cutaneous (dc) SSc, HLA-C*07:01-B*08:01 block to map the susceptibility role of HLA-B*08:01 to develop SSc, and the C*07:02-B*39:05 and C*07:02-B*39:06 blocks to map the protective role of C*07:02 in SSc. We also confirmed previous associations of HLA-DRB1*11:04 and –DRB1*01 to susceptibility to develop SSc. Importantly...
Spermatogonia stem cell (SSC) self-renewal and differentiation are tightly regulated processes that ensure a continued production of mature sperm throughout male adulthood. In the present study, we investigated the role of glucocorticoid-induced leucine zipper (GILZ) in maintenance of the male germline and spermatogenesis. GILZ was detectable in germ cells of wild type mice on the day of birth, suggesting a role for GILZ in prospermatogonia and SSC pool formation. Gilz KO mice were generated and adult males were azoospermic and sterile. During the first wave of spermatogenesis in Gilz KO mice, spermatogenesis arrested part way through pachytene of meiosis I. Subsequent waves resulted in a progressive depletion of germ cells through apoptosis to ultimately produce a Sertoli cell-only phenotype. Further, in contrast to wild type littermates, PLZF(+) cells were detected in the peri-luminal region of Gilz KO mice at day 6 post-natal, suggesting a defect in prospermatogonia migration in the absence of GILZ. At age 30 days, transient accumulation of PLZF(+) cells in a subset of tubules and severely compromised spermatogenesis were observed in Gilz KO mice, consistent with defective SSC differentiation. GILZ deficiency was associated with an increase in FOXO1 transcriptional activity...
Higher compliance with Surviving Sepsis Campaign (SSC) recommendations has been associated with lower mortality. The authors evaluate differences in compliance with SSC 6-hour bundle according to hospital entrance time (day versus night) and its impact on hospital mortality.
Prospective cohort study of all patients with community-acquired severe sepsis admitted to the intensive care unit of a large university tertiary care hospital, over 3.5 years with a follow-up until hospital discharge. Time to compliance with each recommendation of the SSC 6-hour bundle was calculated according to hospital entrance period: day (08:30 to 20:30) versus night (20:30 to 08:30). For the same periods, clinical staff composition and the number of patients attending the emergency department (ED) was also recorded.
In this period 300 consecutive patients were included. Compliance rate was (night vs. day): serum lactate measurement 57% vs. 49% (P = 0.171), blood cultures drawn 59% vs. 37% (P < 0.001), antibiotics administration in the first 3 hours 33% vs. 18% (P = 0.003), central venous pressure >8 mmHg 45% vs. 29% (P = 0.021), and central venous oxygen saturation (SvcO2) >70%, 7% vs. 2% (P = 0.082); fluids were administered in all patients with hypotension in both periods and vasopressors were administered in patients with hypotension not responsive to fluids in 100% vs. 99%. Time to get specific actions done was also different (night vs. day): serum lactate measurement (4.5 vs. 7 h...
Systemic sclerosis (SSc) is a connective tissue disease in which immune system activation is evidenced by high levels of different cytokines in the sera and/or in the supernatants of cultured peripheral blood mononuclear cells (PBMC) and by the presence of specific autoantibodies. γ/δ T cells accumulate in the lung and the skin of SSc patients suggesting their potential role in the development and maintenance of the disease. The aim of this study was to assess cytokine production and cytotoxic activity of circulating γ/δ T lymphocytes obtained from SSc patients and to evaluate their potential role during this disorder. Our results showed that both the proportion and the absolute number of IFN-γ γ/δ-producing cells (i.e. displaying a Th1 polarization) in SSc was significantly higher than either the proportion and the absolute number of IL-4 γ/δ-producing cells in SSc or the proportion and the absolute number of IFN-γ γ/δ-producing cells in healthy controls (P < 0·05 for both groups). Furthermore, the cytotoxic activity of enriched γ/δ T cells was significantly increased in SSc patients compared with controls. The results concerning the Vδ1+ T cell subset paralleled those of total γ/δ T lymphocytes. In contrast, α/β T cells from SSc and control subjects displayed Th2 cytokine production. All these findings were independent of both disease subset and clinical status. Our data demonstrate that...
Monitor of All-sky X-ray Image (MAXI) on the International Space Station
(ISS) has two kinds of X-ray detectors: the Gas Slit Camera (GSC) and the
Solid-state Slit Camera (SSC). SSC is an X-ray CCD array, consisting of 16
chips, which has the best energy resolution as an X-ray all-sky monitor in the
energy band of 0.5 to 10 keV. Each chip consists of 1024x1024 pixels with a
pixel size of 24$\mu$m, thus the total area is ~200 cm^2. We have developed an
engineering model of SSC, i.e., CCD chips, electronics, the software and so on,
and have constructed the calibration system. We here report the current status
of the development and the calibration of SSC.; Comment: To appear in the Proc. of "MAXI Workshop on AGN Variability", 10-11
March 2001, Nikko, Japan (5 pages, 5 Figs, requires psbox.sty), also found in
Observations of blazar flaring states reveal remarkably different variability
time scales. Especially rapid flares with flux doubling time scales of the
order of minutes have been puzzling for quite some time. Many modeling attempts
use the well known linear relations for the cooling and emission processes in
the jet in a steady-state scenario, albeit the obvious strongly time-dependent
nature of flares. Due to the feedback of self-produced radiation with
additional scattering by relativistic electrons, the synchrotron-self Compton
(SSC) effect is inherently time-dependent. Although this feedback is usually
implemented in numerical treatments, only recently an analytical analysis of
the effects of this nonlinear behaviour has been performed. Here, we report our
results concerning the effect of the time-dependent SSC on the spectral energy
distribution (SED) of blazars. We calculated analytically the synchrotron and
the SSC component, giving remarkably different spectral features compared to
the standard linear approach. Adding an external photon field to the original
setting, we could implement quite easily the effect of an additional external
Compton (EC) cooling, since such strong external photon fields are observed in
flat spectrum radio quasars (FSRQ)...
The synchrotron-self Compton (SSC) radiation process is widely held to
provide a close representation of the double peaked spectral energy
distributions from BL Lac Objects (BL Lacs), which are marked by non-thermal
beamed radiations, highly variable on timescales of days or less. Their
outbursts in the gamma ray relative to the optical/X rays might be surmised to
be enhanced in BL Lacs as these photons are upscattered via the inverse Compton
(IC) process. From the observed correlations among the spectral parameters
during optical/X-ray variations we aim at predicting corresponding correlations
in the gamma-ray band, and the actual relations between the gamma-ray and the
X-ray variability consistent with the SSC emission process. We start from the
homogeneous single-zone SSC source model, with log-parabolic energies
distributions of emitting electron as required by the X-ray data of many
sources. We find relations among spectral parameters of the IC radiation in
both the Thomson (for Low energy BL Lacs) and the Klein-Nishina regimes (mainly
for High energy BL Lacs) and we compute how variability is driven by a smooth
increase of key source parameters, primarily the root mean square electron
energy. The single component SSC source model in the Thomson regime turns out
to be adequate for many LBL sources. However...
The origin of the high-energy component in spectral energy distributions
(SED) of blazars is still a bit of a mystery. While BL Lac objects can be
rather successfully modelled within the one-zone synchrotron self-Compton (SSC)
scenario, the SED of low peaked Flat Spectrum Radio Quasars (FSRQ) is more
difficult to reproduce. Their high-energy component needs the abundance of
strong external photon sources, giving rise to stronger cooling via the inverse
Compton channel, and thusly to a powerful component in the SED. Recently, we
were able to show that such a powerful inverse Compton component can also be
achieved within the SSC framework. This, however, is only possible if the
electrons cool by SSC, which results in a non-linear process, since the cooling
depends on an energy integral over the electrons. In this paper we aim to
compare the non-linear SSC framework with the external Compton (EC) output by
calculating analytically the external Compton component with the underlying
electron distribution being either linearly or non-linearly cooled. Due to the
additional linear cooling of the electrons with the external photons, higher
number densities of electrons are required to achieve non-linear cooling,
resulting in more powerful inverse Compton components. If the electrons
initially cool non-linearly...
The broadband SEDs of blazars show two distinct components which in leptonic
models are associated with synchrotron and SSC emission of highly relativistic
electrons. In some sources the SSC component dominates the synchrotron peak by
one or more orders of magnitude implying that the electrons mainly cool by
inverse Compton collisions with their self-made synchrotron photons. Therefore,
the linear synchrotron loss of electrons, which is normally invoked in emission
models, has to be replaced by a nonlinear loss rate depending on an energy
integral of the electron distribution. This modified electron cooling changes
significantly the emerging radiation spectra. It is the purpose of this work to
apply this new cooling scenario to relativistic power-law distributed
electrons, which are injected instantaneously into the jet. We will first solve
the differential equation of the volume-averaged differential number density of
the electrons, and then discuss their temporal evolution. Since any non-linear
cooling will turn into linear cooling after some time, we also calculated the
electron number density for a combined cooling scenario consisting of both the
linear and non-linear cooling. For all cases, we will also calculate
analytically the emerging optically thin synchrotron fluence spectrum which
will be compared to a numerical solution. For small normalized frequencies f <
1 the fluence spectra show constant spectral indices. We find for linear
cooling a_SYN = 1/2...
Aims: We investigate the role of the second synchrotron self-Compton (SSC)
photon generation to the multiwavelength emission from the compact regions of
sources that are characterized as misaligned blazars. For this, we focus on the
nearest high-energy emitting radio galaxy Centaurus A and we revisit the
one-zone SSC model for its core emission. Methods: We have calculated
analytically the peak luminosities of the first and second SSC components by,
first, deriving the steady-state electron distribution in the presence of
synchrotron and SSC cooling and, then, by using appropriate expressions for the
positions of the spectral peaks. We have also tested our analytical results
against those derived from a numerical code where the full emissivities and
cross-sections were used. Results: We show that the one-zone SSC model cannot
account for the core emission of Centaurus A above a few GeV, where the peak of
the second SSC component appears. We, thus, propose an alternative explanation
for the origin of the high energy ($\gtrsim 0.4$ GeV) and TeV emission, where
these are attributed to the radiation emitted by a relativistic proton
component through photohadronic interactions with the photons produced by the
primary leptonic component. We show that the required proton luminosities are
not extremely high...