356 resultados para Speculation.
Resumo:
Since the Sarbanes-Oxley Act was passed in 2002, it has become commonplace in the advertising industry to use creativity-award-show prizes instead of gross income figures to attract new customers. Therefore, achieving a top creativity ranking and winning creativity awards have become high priorities in the advertising industry. Agencies and marketers have always wondered what elements in the advertising creation process would lead to the winning of creativity awards. Although this debate has been dominated by pure speculation about the success of different routines, approaches and strategies in winning creativity awards, for the first time our study delivers an empirical insight into the key drivers of creativity award success. We investigate what strategies and which elements of an advertising campaign are truly likely to lead to winning the maximum number of creativity awards. Using a sample of 108 campaigns, we identify factors that influence campaign success at international advertising award shows. We identify innovativeness and the integration of multiple channels as the key drivers of creativity award success. In contrast to industry beliefs, meaningful or personally connecting approaches do not seem to generate a significant benefit in terms of winning creativity awards. Finally, our data suggest that the use of so-called “fake campaigns” to win more creativity awards does not prove to be effective.
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Ice streams are a fact of ice-sheet dynamics, draining up to 90% of the ice. Thermal convection in ice below the density inversion is a speculation. An attempt is made to meld the two in such a way that the speculation becomes an explanation for the fact.
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In 1846, T. Wharton-Jones described a coarsely granular stage in the development of granulocytic cells in animal and human blood. Shortly thereafter, Max Schultze redefined the coarsely granular cells as a type distinct from finely granular cells, rather than just a developmental stage. It was, however, not until 1879, when Paul Ehrlich introduced a method to distinguish granular cells by the staining properties of their granules, that a classification became possible. An intensive staining for eosin, among other aniline dyes, was eponymous for the coarsely granular cell type, which thereupon became referred to as eosinophil granulocyte. Eosinophilia had already been described in many diseases by the late 19th century. The role of these cells, however, today remains a matter of continuing speculation and investigation. Many functions have been attributed to the eosinophil over the years, often linked to increasing knowledge about the granular and cytoplasmatic contents. A better understanding of the regulatory mechanisms of eosinopoiesis has led to the development of knock-out mice strains as well as therapeutic strategies for reducing the eosinophil load in patients. The effect of these therapeutics and the characterization of the knock-out phenotypes have led to a great increase in the knowledge of the role of the eosinophil in disease. Today we think of the eosinophil as a multifunctional cell involved in host defense, tissue damage and remodeling, as well as immunomodulation.
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OBJECTIVE The objective of the study is to investigate the electrocortical and the global cognitive effects of 3 months rivastigmine medication in a group of mild to moderate Alzheimer's disease patients. MATERIALS AND METHODS Multichannel EEG and cognitive performances measured with the Mini Mental State Examination in a group of 16 patients with mild to moderate Alzheimer's Disease were collected before and 3 months after the onset of rivastigmine medication. RESULTS Spectral analysis of the EEG data showed a significant power decrease in the delta and theta frequency bands during rivastigmine medication, i.e., a shift of the power spectrum towards 'normalization'. Three-dimensional low resolution electromagnetic tomography (LORETA) functional imaging localized rivastigmine effects in a network that includes left fronto-parietal regions, posterior cingulate cortex, bilateral parahippocampal regions, and the hippocampus. Moreover, a correlation analysis between differences in the cognitive performances during the two recordings and LORETA-computed intracortical activity showed, in the alpha1 frequency band, better cognitive performance with increased cortical activity in the left insula. CONCLUSION The results point to a 'normalization' of the EEG power spectrum due to medication, and the intracortical localization of these effects showed an increase of cortical activity in frontal, parietal, and temporal regions that are well-known to be affected in Alzheimer's disease. The topographic convergence of the present results with the memory network proposed by Vincent et al. (J. Neurophysiol. 96:3517-3531, 2006) leads to the speculation that in our group of patients, rivastigmine specifically activates brain regions that are involved in memory functions, notably a key symptom in this degenerative disease.
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Loss of appetite and ensuing weight loss is a key feature of severe illnesses. Protein-energy malnutrition (PEM) contributes significantly to the adverse outcome of these conditions. Pharmacological interventions to target appetite stimulation have little efficacy but considerable side effects. Therefore nutritional therapy appears to be the logical step to combat inadequate nutrition. However, clinical trial data demonstrating benefits are sparse and there is no current established standard algorithm for use of nutritional support in malnourished, acutely ill medical inpatients. Recent high-quality evidence from critical care demonstrating harmful effects when parenteral nutritional support is used indiscriminately has led to speculation that loss of appetite in the acute phase of illness is indeed an adaptive, protective response that improves cell recycling (autophagy) and detoxification. Outside critical care, there is an important gap in high quality clinical trial data shedding further light on these important issues. The selection, timing, and doses of nutrition should be evaluated as carefully as with any other therapeutic intervention, with the aim of maximising efficacy and minimising adverse effects and costs. In light of the current controversy, a reappraisal of how nutritional support should be used in acutely ill medical inpatients outside critical care is urgently required. The aim of this review is to discuss current pathophysiological concepts of PEM and to review the current evidence for the efficacy of nutritional support regarding patient outcomes when used in an acutely ill medical patient population outside critical care.
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We have identified benthic recruitment habitats and nursery grounds of the American lobster Homarus americanus Milne Edwards in the coastal Gulf of Maine, USA, by systematically censusing subtidal sediment, cobble, and ledge substrata. We distinguish lobsters between settlement size (5 mm carapace length (CL) to ca 40 mm CL as the 'early benthic phase' (EBP) because they are ecologically and behaviorally distinct from larger lobsters. EBP lobsters are cryptic and apparently restricted to shelter-providing habitats (primarily cobble substratum) in coastal Gulf of Maine. In these habitats we found average population densities of EBP lobsters as high as 6.9 m-2. EBP lobsters were virtually absent from ledge and sedimentary substrata devoid of vegetation although larger lobsters are commonly found there. It is possible that the requirement for shelter-providing substrata by this life phase creates a natural demographic 'bottleneck' to benthic recruitment for the species. Prime cobble recruitment habitat is relatively rare and comprises ca 11 % of the 60.2 km of shoreline at our study area in midcoast Maine. If this low availability of cobble exists throughout the Gulf of Maine, as other studies indicate, it could limit lobster production potential. We verified the geographic extent of recruitment to cobble habitats censused in 3 of 4 regions spanning ca 300 km of the coastal Gulf of Maine (from Nahant, Massachusetts to Swans Island, Maine). Early benthic phase lobsters were absent from cobble censused in the northeastern extreme of our survey (Swans Island). This pattern is consistent with earlier speculation that relatively cool water temperatures may limit larval settlement in this region.
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To better understand the mechanisms of how the human prostacyclin receptor (1P) mediates vasodilation and platelet anti-aggregation through Gs protein coupling, a strategy integrating multiple approaches including high resolution NMR experiments, synthetic peptide, fluorescence spectroscopy, molecular modeling, and recombinant protein was developed and used to characterize the structure/function relationship of important segments and residues of the IP receptor and the α-subunit of the Gs protein (Gαs). The first (iLP1) and third (iLP3) intracellular loops of the IP receptor, as well as the Gαs C-terminal domain, relevant to the Gs-mediated IP receptor signaling, were first identified by observation of the effects of the mini gene-expressed corresponding protein segments in HEK293 cells which co-expressed the receptor and Gαs. Evidence of the IP iLP1 domain interacted with the Gαs C-terminal domain was observed by fluorescence and NMR spectroscopic studies using a constrained synthetic peptide, which mimicked the IP iLP1 domain, and the synthetic peptide, which mimicked Gαs C-terminal domain. The solution structural models and the peptide-peptide interaction of the two synthetic protein segments were determined by high resolution NMR spectroscopy. The important residues in the corresponding domains of the IP receptor and the Gαs predicted by NMR chemical shift mapping were used to guide the identification of their protein-protein interaction in cells. A profile of the residues Arg42 - Ala48 of the IP iLP1 domain and the three residues Glu392 ∼ Leu394 of the Gαs C-terminal domain involved in the IP/Gs protein coupling were confirmed by recombinant proteins. The data revealed an intriguing speculation on the mechanisms of how the signal of the ligand-activated IP receptor is transmitted to the Gs protein in regulating vascular functions and homeostasis, and also provided substantial insights into other prostanoid receptor signaling. ^
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Mammalian cells express 7 β-tubulin isotypes in a tissue specific manner. This has long fueled the speculation that different isotypes carry out different functions. To provide direct evidence for their functional significance, class III, IVa, and VI β-tubulin cDNAs were cloned into a tetracycline regulated expression vector and stably transfected Chinese hamster ovary cell lines expressing different levels of ectopic β-tubulin were compared for effects on microtubule organization, microtubule assembly and sensitivity to antimitotic drugs. It was found that all three isotypes coassembled with endogenous β-tubulin. βVI expression caused distinct microtubule rearrangements including microtubule dissociation from the centrosome and accumulation at the cell periphery; whereas expression of βIII and βVIa caused no observable changes in the interphase microtubule network. Overexpression of all 3 isotypes caused spindle malformation and mitotic defects. Both βIII and βIVa disrupted microtubule assembly in proportion to their abundance and thereby conferred supersensitivity to microtubule depolymerizing drugs. In contrast, βVI stabilized microtubules at low stoichiometry and thus conferred resistance to many microtubule destabilizing drugs but not vinblastine. The 3 isotypes caused differing responses to microtubule stabilizing drugs. Expression of βIII conferred paclitaxel resistance while βVI did not. Low expression of βIVa caused supersensitivity to paclitaxel, whereas higher expression resulted in the loss of supersensitivity. The results suggest that βIVa may possess an enhanced ability to bind paclitaxel that increases sensitivity to the drug and acts substoichiometrically. At high levels of βVIa expression, however, microtubule disruptive effects counteract the assembly promoting pressure exerted by increased paclitaxel binding, and drug supersensitivity is lost. From this study, I concluded that β-tubulin isotypes behave differently from each other in terms of microtubule organization, microtubule assembly and dynamics, and antimitotic drug sensitivity. The isotype composition of cell can impart subtle to dramatic effects on the properties of microtubules leading to potential functional consequences and opening the opportunity to exploit differences in microtubule isotype composition for therapeutic gain. ^
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Asthma is a significant public health issue and the most common chronic disease in children. The disease burden of asthma is rising around the world and especially in certain populations. In the United States Puerto Rican Americans have the highest rates of mortality due to asthma, while Mexico Americans have the lowest asthma mortality in the U.S. The reasons for this have been the cause of much speculation in the past; however, no clear cause for these differences has been recognized. The present work reviews the literature bearing on this question to show that there are good reasons to believe that individuals with unusually responsive innate immune responses may be predisposed to the development of asthma. Also reviewed is the molecular basis for this connection. The evidence shows that the history and anthropology of the Puerto Rican people is quite different from that of any other surviving North American or Caribbean population, as it was a relatively isolated island population for 400 years with an environment that tended to eliminate individuals with weak innate immune systems. The Puerto Rican population successfully survived the Columbian exchange of microbes but may be poorly adapted to the modern pro-inflammatory diet coupled with exposure to cigarette smoke as well as cockroach and house dust mite feces.^
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This research study offers a critical assessment of NIH's Consensus Development Program (CDP), focusing upon its historical and valuative bases and its institutionalization in response to social and political forces. The analysis encompasses systems-level, as well as interpersonal factors in the adoption of consensus as the mechanism for resolving scientific controversies in clinical practice application. Further, the evolution of the CDP is also considered from an ecological perspective as a reasoned adaptation by NIH to pressures from its supporters and clients for translating biomedical research into medical practice. The assessment examines federal science policy and institutional designs for the inclusion of the public interest and democratic deliberation.^ The study relies on three distinct approaches to social research. Conventional historical methods were utilized in the interpretation of social and political influences across eras on the evolution of the National Institutes of Health and its response to demands for accountability and relevance through its Consensus Development Program. An embedded single-case study was utilized for an empirical examination of the CDP mechanism through five exemplar conferences. Lastly, a sociohistorical approach was taken to the CDP in order to consider its responsiveness to the values of the eras which created and shaped it. An exploration of organizational behavior with considerations for institutional reform as a response to continuing political and social pressure, it is a study of organizational birth, growth, and response to demands from its environment. The study has explanatory import in its attempt to account for the creation, timing, and form of the CDP, relative to political, institutional, and cultural pressures, and predictive import thorough its historical view which provides a basis for informed speculation on the playing out of tensions between extramural and intermural scientists and the current demands for health care reform. ^
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A community development program operating in the mountains of North India was studied to assess its potential effects on mortality, fertility and migration patterns in the community which it served. The development program operated in Jaunpur Block, Tehri-Garhwal District, Uttar Pradesh State. Two comparable villages in the district were studied. The development program had been working in one for two years, and the other was completely untouched by the program.^ Since not enough time had elapsed since the beginning of the development program's work for any effects on demographic patterns to be visable in Jaunpur Block, this study looked to attitudes of village residents as indicators of future demographic trends. Existing demographic patterns and their interrelationship with socio-religious customs were examined in the test village. A questionnaire was then administered to ascertain attitudinal differences between the residents of the test village and the control village.^ The primary work of the community development program was to train women as village health workers. The results of the attitudinal comparison of the residents of the two villages showed a marked difference in attitudes relating to the position of women in society. The data showed a higher esteem for women in the test village than in the control village, and it is argued that this difference may be attributable to the work of the development program.^ Predicting future demographic trends in Jaunpur Block on the basis of the observed difference in villagers' attitudes toward the status of women is speculatory. Jaunpur Block appears to be in the demographic stage of pre-transition, maintaining relatively high rates of both mortality and fertility. Based on demographic transition theory the next significant change in demographic patterns in Jaunpur is predicted to be a decline in mortality, and an increase in the status of women is unrelated to this prediction.^ The community development program which was studied terminated unexpectedly during the time of this study. A case study of the program's final months is presented, and speculation on the future course of demographic trends in Jaunpur Block is related to the possible alternatives for future development in the area. ^
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Allergen-induced asthma is the leading form of asthma and a chronic condition worldwide. Common allergens are known to contribute to the pathogenesis of this disease. Murine models of allergic asthma have mostly used an intraperitoneal route of sensitization (not airway) to study this disease. Allergic asthma pathophysiology involves the activation of TH2-specific cells, which triggers production of IgE antibodies, the up-regulation of TH2-specific cytokines (i.e. IL-4, IL-5, IL-9 and IL-13), increased airway eosinophilia, and mucin hypersecretion. Although there are several therapeutics currently treating asthmatic patients, some of these treatments can result in drug tolerance and may be linked to increased mortality. CpG oligodeoxynucleotides (ODNs) is a synthetic ligand that targets Toll-like Receptor (TLR) 9. It has been evaluated as a therapeutic agent for the treatment of cancer, infectious diseases, and for treating allergy and asthma. PUL-042 is also a synthetic TLR ligand and is composed of two agonists against TLR2/6 heterodimer and TLR9. Previous studies have evaluated PUL-042 for its ability to confer resistance against bacterial and viral lung infection. These findings, combined with studies performed using CpG ODNs, led to speculation that PUL-042 dampens the immune response in allergen-induced asthma. My thesis research investigated airway route sensitization and airway delivery of PUL-042 to evaluate its effects in reducing an allergen-induced asthma phenotype in a murine model. The results of this study contribute to the foundation for future investigations to evaluate the efficacy of PUL-042 as a novel therapy in allergic-asthma disease.
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SHP1 is a cytosolic protein tyrosine phosphatase that contains two SH2 domains. It is highly expressed in hematopoietic cells and expressed in normal epithelium at lower levels. While SHP1 in hematopoietic cells is thought to be a negative regulator of cellular signaling by associating with and dephosphorylating various receptors and their downstream effectors after they become activated, its precise function in epithelium remains to be understood. The potential involvement of SHP1 in human tumorigenesis has been hypothesized from the findings that SHP1 can interact with, dephosphorylate, and regulate the activity of several protein tyrosine kinases (PTKs) implicated in human cancer. These PTKs include epidermal growth factor receptor (EGFR) and Src. Such speculation is also supported by the report that SHP1 is overexpressed in human ovarian cancers. ^ Here we report, for the first time, that the levels of SHP1 expression and activity are altered in human breast cancer cells in comparison with normal breast epithelium. In particular, SHP1 expression is nearly lost in the breast cancer cell lines MDA-MB231 and MDA-MB435. After the re-introduction of SHP1 both in wild type (wt) and enzymatically inactive (dn) forms, into the MDA-MB231 cells, we observed no changes in cellular proliferation. However, the overexpression of wt SHP1 led to increased anchorage-independent growth in the MDA-MB231 cells. SHP1 phosphatase activity is essential for such an increase since the overexpression of dn SHP1 had no effect. Enhanced turnorigenicity in nude mice was also observed in the MDA-MB231 cells overexpressing wt SHP1, but not dn SHP1, suggesting the crucial function of SHP1 enzymatic activity in this process. Our observations in this study indicate that SHP1 promotes tumorigenesis by a mechanism or mechanisms apart from enchancing angiogenesis. In addition, we have found no evidence that the overexpression of SHP1 could affect metastatic potential in the MDA-MB231 cells. ^ In the MDA-MB231 cells stably transfected with either wt or dn SHP1 the peak level of EGFR tyrosine phosphorylation induced by EGF, as well as the sensitivity to EGF stimulation, was not altered. However, the overexpression of wt SHP1 led to a slight increase in the kinetics of EGFR dephosphorylation, whereas the overexpression of dn SHP1 led to slightly delayed kinetics of EGFR dephosphorylation. The overexpression of either the wt or dn SHP1 did not lead to any significant increase in Src kinase activity. ^ In NIH3T3 cells, the transient overexpression of SHP1 led to no significant changes in MAP kinase (ERK2) activation by EGF or Akt activation by PDGF. In 3T3H4 cells, the transient overexpression of SHP1 led to no significant changes in MAP kinase (ERK2) activation by heregulin. The transient overexpression of wt SHP1 in the MDA-MB231 cells caused an apparent increase, ranging from 10% to 20%, in the G0/G1 population of the cells with a corresponding decrease in the S phase population. ^ In order to understand the mechanisms by which SHP1 exerts its positive effect on the tumorigenic potential of the MDA-MB231 cells, we employed two-dimensional electrophoresis in an attempt to identify cellular protein(s) with significantly altered tyrosine phosphorylation level upon wt SHP1 overexpression. The overexpression of wt SHP1 but not dn SHP1, leads increased tyrosine phosphorylation of a protein with a molecular weight of approximately 40 kDa and a pI between 5.9 to 6.6. ^
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Benthic foraminiferal assemblages are a widespread tool to understand changes in organic matter flux and bottom-water oxygenation and their relation to paleoceanographic changes in the Upper Cretaceous oceans. In this study, assemblage data (diversity, total number, and number per species and gram) from Deep Sea Drilling Project (DSDP) Site 390 (Blake Nose, western North Atlantic) were processed for the lower Maastrichtian (Globotruncana falsostuarti - Gansserina gansseri Planktic Foraminiferal Zone). These data document significant changes in nutrient flux to the sea floor as well as bottom-water oxygenation during this time interval. Parallel to the observed changes in the benthic foraminiferal assemblages the number of inoceramid shells decreases, reflecting also a significant increase in bottom-water oxygenation. We speculate, that these data could reflect the onset of a shift from warmer low-latitude to cooler high-latitude deep-water sources. This speculation will predate the major reorganization of the oceanic circulation resulting in a circulation mode similar to today at the Early/Late Maastrichtian boundary by ~1 Ma and therefore improves our understanding of Late Cretaceous paleoceanography.
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En el año 1979, Abelardo Arias publica su segunda novela de base histórica titulada Inconfidencia (El Aleijadinho), la cual recrea el Brasil imperial de fines del siglo XVIII, ámbito que dio a luz a ese extraño genio de la plástica que fue el mestizo Antonio Francisco de Lisboa, "el Aleijadihno ". Arias elude la facilidad de la biografia novelada y logra acercarse al escultor leproso desde su propia tensión de artista. Comprende, por ello, su tortuosa vida de marginado y hombre desengañado del amor, que vuelca su existencia a la creación estética. La relación que el Aleijadihno tiene con su obra, oscilante entre la exaltación religiosa y la pasión amorosa, nos lleva a estudiar en profundidad las líneas de tensión en torno de la correspondencia entre arte mayor y religiosidad. Como señala Abel Posse al respecto: "El gran artista (el Aleijadihno) tiende a fundar su obra alrededor de un weltanschaung o cosmovisión total y esta ambición lo acerca al mundo religioso y a la especulación metafisica ". La obra, por lo tanto, desarrolla una silenciosa agonia existencial y religiosa, el combate callado de un "alejado ", de un condenado a muerte.