Miracle-dz/UniFAR-FTUs huggingface dataset:
The cellular phenotype of AZ703, a novel selective imidazo[1,2-a]pyridine cyclin-dependent kinase inhibitor

Because the majority of cancers exhibit direct or indirect deregulation of cyclin-dependent kinase (CDK) function, members of the CDK family are attractive targets for the development of anticancer agents. As part of an ongoing program, novel imidazopyridines were identified and developed as potent and selective CDK inhibitors. Here, we describe data on the in vitro biological activities of one of these compounds, AZ703. The selectivity profile of AZ703 was investigated in kinase assays against a range of CDK enzymes as well as a panel of protein kinases in vitro. IC50s were assessed against different tumor cell lines in vitro. The mechanism of action of AZ703 was determined by observing changes in phosphorylation of CDK substrates and cell cycle effects on tumor and normal cells. In vitro studies revealed that AZ703 is a selective inhibitor of CDK1 and CDK2 and displays a mode of action consistent with the induction of G1-, S-, and G2-M-phase arrest. AZ703 also showed potent antiproliferative activity across a wide range of tumor cell lines in vitro. Moreover, AZ703 induced reversible blockade of normal cells while causing tumor cells to undergo apoptosis. We have identified AZ703 as a novel selective imidazo[1,2-a]pyridine CDK inhibitor that shows promising antitumor properties in vitro. [Mol Cancer Ther 2006;5(3):655–64]
CYD-TDV dengue vaccine: systematic review and meta-analysis of efficacy, immunogenicity and safety.

INTRODUCTION Dengue virus (DENV) is a serious global health problem. CYD-TDC (Dengvaxia®) was the first vaccine to gain regulatory approval to try and address this problem. AIM Summarize all available evidence on the immunogenicity, efficacy and safety of the CYD-TDV dengue vaccine. METHOD Meta-analysis and systematic review. RESULTS The best and worst immunogenicity results were for DENV4 and DENV1, respectively. Vaccine efficacy of 60% was derived from studies with participants aged 2-16 years old, with DENV4 and DENV2 presenting the best and worst results, respectively. Erythema and swelling were more frequent with CYD-TDV. No differences were detected for systemic adverse events. CONCLUSION CYD-TDV showed moderate efficacy in children and adolescents. From the immunogenicity results in adults, we can expect satisfactory efficacy from vaccination in this population.
Hormone Therapy Use and Breast Cancer Incidence by Histological Subtypes in Sweden and Norway

Abstract: Mammography screening and postmenopausal hormone therapy (HT) both influence breast cancer incidence. While breast cancer incidence increased by around 50% during the introduction of screening, a smaller decline in incidence has been reported in several countries after 2002 when the sales of HT started to decline. Data suggest that HT increases the risk of the second most common type of breast cancer, invasive lobular carcinoma (ILC) but not the most common, invasive ductal carcinoma (IDC). Breast cancer incidences stratified on histological subtypes were obtained from the national cancer registries. HT sales data from drug consumption statistics and information on the county‐level introduction of mammography screening were combined, and breast cancer incidence trends were estimated using Poisson regression models, focusing on the period after 2002. From 2002 to 2007 the annual decrease in breast cancer incidence rates for women aged 50–69 was 1.5% (95% CI −2.3% to −0.7%) in Sweden and 0.8% (95% CI −2.8% to 1.2%) in the part of Norway not confounded by prevalence screening. Most of the decline was in the rates of ILC which dropped by 4.7% (95% CI −6.6% to −2.7%) and 7.0% (95% CI −12.8% to −0.9%) per year, respectively. The rates of IDC were stable in this period. Breast cancer incidence has declined in Sweden and Norway since 2002, but the reduction is moderate compared with the large increase that occurred during the introduction of mammography screening. Declining rates of ILC, but not of IDC, support the hypothesis that the drop in breast cancer incidence is associated with reduced HT use.
Model based visual inspection of pharmaceutical tablets with photometric stereo

A model based visual inspection of pharmaceutical tablets is proposed for the detection of surface defects that occur during the tableting process. A novel RB-BR photometric stereo configuration is used to obtain four images for every tablet at different lighting orientations. During the inspection, reconstructed 3D depth maps derived from acquired images are compared to the tablet model, obtained during the training phase. Inspected tablets are classified as defective if the difference exceeds a predefined threshold. The approach was tested on two sets of tablets and compared to the current state of the art methods. The results yield 89 % and 87 % successful defect detection rate for tablets without and with embossing, respectively.
Social Democrats in Government and the Variety of Capitalism in the Czech Republic

Social Democrats in Government and the Variety of Capitalism in the Czech Republic Social Democrats dominated the Czech government from 1998 to 2006. Their impact on the type of capitalism in that country is analysed with an adaptation of established approaches to varieties of capitalism. Vaguely defined neo-liberal and social-democratic trends reached an implicit compromise after 1989, but economic difficulties led to a reopening of basic questions after 1998. The Social Democrats drew inspiration primarily from western European allies. The most open conflicts affecting the type of capitalism centred on the state budget. Without a parliamentary majority, the Social Democrats had to seek compromises and choose priorities such that the budget was central to developments in other spheres. The dominant trend in the business sphere was towards foreign ownership, leading to a weakening of trade union influence in the employment relations sphere and in political life in general. Weaker unions meant weaker opposition to neo-liberal pressures in the welfare sphere, but the Social Democrats resisted pressures for dismantling the
Hepatocyte nuclear factor 1α and β control terminal differentiation and cell fate commitment in the gut epithelium

The intestinal epithelium is a complex system characterized by massive and continuous cell renewal and differentiation. In this context, cell-type-specific transcription factors are thought to play a crucial role by modulating specific transcription networks and signalling pathways. Hnf1α and β are closely related atypical homeoprotein transcription factors expressed in several epithelia, including the gut. With the use of a conditional inactivation system, we generated mice in which Hnf1b is specifically inactivated in the intestinal epithelium on a wild-type or Hnf1a−/− genetic background. Whereas the inactivation of Hnf1a or Hnf1b alone did not lead to any major intestinal dysfunction, the concomitant inactivation of both genes resulted in a lethal phenotype. Double-mutant animals had defective differentiation and cell fate commitment. The expression levels of markers of all the differentiated cell types, both enterocytes and secretory cells, were affected. In addition, the number of goblet cells was increased, whereas mature Paneth cells were missing. At the molecular level, we show that Hnf1α and β act upstream of the Notch pathway controlling directly the expression of two crucial components: Jag1 and Atoh1. We demonstrate that the double-mutant mice present with a defect in intestinal water absorption and that Hnf1α and β directly control the expression of Slc26a3, a gene whose mutations are associated with chloride diarrhoea in human patients. Our study identifies new direct target genes of the Hnf1 transcription factors and shows that they play crucial roles in both defining cell fate and controlling terminal functions in the gut epithelium.
Different cytokine profiles in patients with a history of gangrenous or phlegmonous appendicitis

Appendicitis is one of the most common and costly acute abdominal states of illnesses. Previous studies suggest two types of appendicitis which may be different entities, one which may resolve spontaneously and another that progresses to gangrene and perforation. Gangrenous appendicitis has a positive association to states of Th1 mediated immunity whereas Th2 associated immune states are associated with lower risk of appendicitis. This study investigated the inflammatory response pattern in patients previously appendicectomized for gangrenous (n = 7), or phlegmonous appendicitis (n = 8) and those with a non‐inflamed appendix (n = 5). Peripheral blood mononuclear cells were analysed with ELISPOT analysis for number of spontaneous or antigen/mitogen stimulated IFN‐γ, IL‐4, IL‐10 and IL‐12 secreting cells or with ELISA for concentration of spontaneous or antigen/mitogen stimulated IFN‐γ, IL‐5 and IL‐10. Spontaneously IL‐10 secreting cells/100 000 lymphocytes were increased in the gangrenous group compared to the phlegmonous group (P = 0·015). The median concentration of IL‐10 secreted after Tetanus toxoid (TT)‐stimulation were higher in the gangrenous group and the control group, than the phlegmonous group (P = 0·048 and P = 0·027, respectively). The median concentration of TT induced IFN‐γ secretion was higher for the gangrenous group compared to both the phlegmonous group and the control group (P = 0·037 and P = 0·003). Individuals with a history of gangrenous appendicitis demonstrated ability to increased IL‐10 and IFN‐γ production. The increased IFN‐γ may support the notion of gangrenous appendicitis as an uncontrolled Th1 mediated inflammatory response and increased IL‐10 may speculatively indicate the involvement of cytotoxic cells in the progression to perforation.
Salivary and Serum Markers Related to Innate Immunity in Generalized Aggressive Periodontitis

BACKGROUND Host inflammatory and immune responses play an important role in aggressive periodontitis (AgP). Thus, this study aims to evaluate levels of the innate immunity-related markers calprotectin, colony-stimulating factor (CSF)-1, macrophage migration inhibitory factor (MIF), monokine induced by interferon-γ (MIG), and matrix metalloproteinase (MMP)-8 in serum and saliva from patients with generalized AgP and those with gingivitis or a healthy periodontium. METHODS This study enrolled 40 individuals (17 males and 23 females; mean age 33.30 ± 9.31 years), 15 with generalized AgP, 15 with gingivitis, and 10 who were periodontally healthy. Full-mouth periodontal examinations were performed, and serum and saliva were collected. Levels of calprotectin, CSF-1, MIF, MIG, and MMP-8 were measured using enzyme-linked immunosorbent assays. RESULTS In serum, mean levels of calprotectin were 2.06-fold higher in patients with AgP than in healthy patients (P = 0.01). Serum levels of MMP-8 were significantly elevated in patients with AgP compared with both healthy patients and those with gingivitis, by 2.60-fold and 2.77-fold, respectively (P = 0.03 and P = 0.009, respectively). In saliva, levels of MMP-8 were 5.66-fold higher in patients with AgP than in healthy patients (P = 0.02). CSF-1, MIF, and MIG levels in both serum and saliva did not differ significantly among the groups. CONCLUSIONS Serum levels of calprotectin and MMP-8 are elevated in patients with AgP. MMP-8 levels are also increased in saliva from patients with AgP. These results support involvement of innate immune response in the pathogenesis of AgP.
More frequent burning increases vulnerability of Alaskan boreal black spruce forests

Much recent research has investigated the effects of burning on mature black spruce (Picea mariana) forests in interior Alaska, however little research has focused on how frequent reburning affects soil organic layer (SOL) vulnerability in these ecosystems. We compared organic soil layer characteristics in black spruce stands that burned after two fire-free intervals (FFI), including an intermediate-interval (37–52 years) and a more typical long-interval (70–120 years). We found that depth of burn varied significantly between intermediate-interval and long-interval sites, and as there was less material available to burn in intermediate-interval stands, percent depth reduction was greater in these stands (78.9% ± 2.6%) than in long-interval stands (62.9% ± 1.5%). As a result, less residual organic soil carbon remained post-fire in intermediate-interval than long-interval stands. Post-fire organic soil carbon stocks averaged 0.51 ± 0.08 kg C m−2 in the intermediate-interval sites, which is less than estimates of soil carbon stock for long-interval fire events (ranging from 2.07 to 5.74 kg C m−2). In addition to altering soil carbon storage, a depletion of the SOL during more frequent fire events will likely delay the recovery of permafrost and could trigger a change in the possible successional trajectory of a site, from black spruce dominated to deciduous or even shrub dominated ecosystems in the future.
Temporary and permanent components of Colombia's output

Structural time series models, frequency domain analysis, the HP-filetr, and the Blanchard-Quah decomposition, are used to observe, some peculiarities of the business cycle. Such properties are those related the volatility of the temporary component and the duration of the business cycle during both 1925-1994 and 1950-1994. For the longer period we find that cycles between three and six years seem to be the most important for the variability of output; volatility is greater for GDP than for per capita GDP, except when the processes are linearly detrended. For period 1950-1994. GDP, except when the processes are linearly detrended. For period 1950-1994. Although the linear trend plus cycle model does not perform very well, cycles of about eight years seem to be most important for the cycle. The results of the Blanchard and Quah decomposition show that demand shocks have important explanatory attributes for output fluctuations. However, supply shocks, are dominant in the behaviour of output.
From paragraph to graph: Latent semantic analysis for information visualization

Most techniques for relating textual information rely on intellectually created links such as author-chosen keywords and titles, authority indexing terms, or bibliographic citations. Similarity of the semantic content of whole documents, rather than just titles, abstracts, or overlap of keywords, offers an attractive alternative. Latent semantic analysis provides an effective dimension reduction method for the purpose that reflects synonymy and the sense of arbitrary word combinations. However, latent semantic analysis correlations with human text-to-text similarity judgments are often empirically highest at ≈300 dimensions. Thus, two- or three-dimensional visualizations are severely limited in what they can show, and the first and/or second automatically discovered principal component, or any three such for that matter, rarely capture all of the relations that might be of interest. It is our conjecture that linguistic meaning is intrinsically and irreducibly very high dimensional. Thus, some method to explore a high dimensional similarity space is needed. But the 2.7 × 107 projections and infinite rotations of, for example, a 300-dimensional pattern are impossible to examine. We suggest, however, that the use of a high dimensional dynamic viewer with an effective projection pursuit routine and user control, coupled with the exquisite abilities of the human visual system to extract information about objects and from moving patterns, can often succeed in discovering multiple revealing views that are missed by current computational algorithms. We show some examples of the use of latent semantic analysis to support such visualizations and offer views on future needs.
Glucocorticoids and lung development in the fetus and preterm infant

During the final prenatal period of fetal lung development in humans, important maturational processes occur, including the production of surfactant necessary to decrease surface tension at the air‐liquid interface of the alveoli. During early gestation, the glucocorticoid receptor is expressed in the fetal lung, and glucocorticoids stimulate the production of surfactant‐associated proteins and increase phospholipid synthesis by enhancing the activity of phosphatidylcholine. Other glucocorticoid‐induced effects may include stimulation of cell maturation and differentiation, inhibition of DNA synthesis, changes in interstitial tissue components, stimulation of antioxidant enzymes, and regulation of pulmonary fluid metabolism. Recently, it was suggested that glucocorticoids are also important in postnatal pulmonary development, and may be related to the development of neonatal lung disease in preterm infants. Surfactant deficiency that can be prevented by antenatal corticosteroid treatment causes infant respiratory distress syndrome and requires mechanical ventilation. Ventilation by itself or in combination with high levels of oxygen, fluid overload, pulmonary infections, sepsis, and air leak syndrome causes an acute pulmonary inflammatory reaction that may result in chronic lung disease or bronchopulmonary dysplasia. Glucocorticoids are effective in the treatment of chronic lung disease of prematurity and regulate the inflammatory response by the interaction with transcription factors such as nuclear factor κB and activated protein 1. Indeed, inflammatory cells and the levels of chemokines and cytokines in bronchoalveolar fluid decrease after dexamethasone treatment. However, treatment of fetuses and preterm infants with repeated and/or high doses of corticosteroids may have considerable long‐term side effects on somatic, brain, and lung growth. The difficult balance between short‐term gain and the possible long‐term side effects of glucocorticoids in preterms remains a difficult issue. Pediatr Pulmonol. 2001; 32:76–91. © 2001 Wiley‐Liss, Inc.
PROMOTING PRE-SERVICE TEACHERS’ ENGAGEMENT IN PROFESSIONAL LEARNING THROUGH PARTICIPATION IN ONLINE LEARNING COMMUNITY: SUPPORT FROM PRACTITIONERS

There is a growing recognition that learning to teach is a complex process. One of the central problems that pre-service teacher encounter during learning to teach process is the disconnection between the theory and practice. Zeichner (2010) states that lack of collaboration between the university instructors and schools while learning to teach in the university phase leads to a lack of preparation for pre-service teachers. Therefore, there is a need for effective ways to minimize the disconnection between school and university. One method of doing this is by engaging pre-service teachers with practitioners in the course topic during the university phase. Introducing pre-service teachers to practitioners can help them acquire teaching skills, and engaging them in the process of learning to teach. Practitioners can provide an authentic learning activity giving the benefits of enhanced pre-service teacher learning and provision of alternative perspectives to course topic. In recent years, interest in how social network sites can be used in pre-service teachers’ program has increased. Social network site is shifting the ways people communicate, collaborate and learn. Nonetheless, there are obstacles linked with its use in education such as lack of learner engagement. Therefore, there is a need for effective methods to enhance pre-service teachers’ engagement in this online environment. One method of enhancing the pre-service teachers’ engagement is by engaging the pre-service teachers with the online community of practitioners. In fact, little is known about the impact of the presence of practitioners on pre-service teachers’ engagement in social network sites. Therefore, the aim of this poster is to provide a brief overview of a conceptual framework that can be used to examine the presence of practitioners on pre-service teachers’ behavioural, emotional and cognitive engagement. This poster will explain the conceptual framework that used in the study and how social capital theory and community of practice were incorporated into the research design. In addition, it will describe the procedures and design that were adopted in this study. The poster explains how different methods such as social network analysis (SNA), content analysis and interviews can be used to analyse pre-service teachers’ engagement in social network sites. It also provides insights for those who may be considering designing online activities or analysing social interactions that takes place in social network sites. Reference Zeichner, K. (2010). Rethinking the connections between campus courses and field experiences in college and university based teacher education. Journal of Teacher Education, 61, pp.89-99.
Space-surface bistatic SAR-GMTI

A space-surface bistatic SAR-GMTI algorithm is proposed here and the clutter characters are also discussed. Then a reference signal is adopted for range compression, which can make the range cell migration and Doppler centroid decreased largely. Furthermore, the clutter Doppler and phase are analysed as well as the phase difference characteristics, a phase compensation function is constructed for clutter rejection as well. At last, simulation result verifies the effectiveness of the proposed method.
Differences in rates of hypoglycemia and health care costs in patients treated with insulin aspart in pens versus vials

Abstract Objectives: To study whether initiation of insulin aspart therapy with a pen vs. a vial/syringe has an impact on the risk of subsequent hypoglycemic episodes and health care costs. Methods: This was a longitudinal, retrospective analysis of the MarketScan and IMS LifeLink health plan claims databases for patients with type 1 or type 2 diabetes who initiated insulin aspart with a pen or a vial/syringe. Included were adults (≥18 years) who had received no short-acting insulin for the 6 months prior to their index date (date of first claim for either treatment) and who initiated treatment with insulin aspart with a pen or with a conventional vial/syringe during the period from January 1, 2004, through December 31, 2007, based on outpatient pharmacy claims data. Patients were excluded if they did not have at least two claims for the index treatment during the 12 month post-index period. Hypoglycemic episodes were identified by any claim containing a diagnosis code for hypoglycemia. Results: Analyses include 6065 patients in the pen group and 5523 patients in the vial/syringe group in the MarketScan database and 4512 patients in the pen group and 3782 patients in the vial/syringe group in the LifeLink database. Vial/syringe use was associated with 35% greater odds of at least one hypoglycemic episode than pen use in the MarketScan database (P < 0.001) and 44% greater odds in the LifeLink database (P < 0.001). Use of vials/syringes was associated with 89% and 62.7% greater health care costs for hypoglycemic events than use of pens, respectively (P < 0.001 for both databases). Patient groups were subject to selection bias as they did not have random assignment to treatment groups. Conclusions: In two independent claims databases, initiation of insulin aspart treatment with pen was associated with fewer hypoglycemic events and lower diabetes-related health care costs than initiation with vial/syringe.