Miracle-dz/UniFAR-FTUs huggingface dataset:
The role of the molecular footprint of EGFR in tailoring treatment decisions in NSCLC

The majority of patients with non-small-cell lung cancer (NSCLC) present with advanced disease, with targeted therapies providing some improvement in clinical outcomes. The epidermal growth factor receptor (EGFR) tyrosine kinase (TK) plays an important role in the pathogenesis of NSCLC. Tyrosine kinase inhibitors (TKIs), which target the EGFR TK domain, have proven to be an effective treatment strategy; however, patient responses to treatment vary considerably. Therefore, the identification of patients most likely to respond to treatment is essential to optimise the benefit of TKIs. Tumour-associated activating mutations in EGFR can identify patients with NSCLC who are likely to have a good response to TKIs. Nonetheless, the majority of patients relapse within a year of starting treatment. Studies of tumours at relapse have demonstrated expression of a T790M mutation in exon 20 of the EGFR TK domain in approximately 50% of cases. Although conferring resistance to reversible TKIs, these patients may remain sensitive to new-generation irreversible/pan-erb inhibitors. A number of techniques have been employed for genotypic assessment of tumour-associated DNA to identify EGFR mutations, each of which has advantages and disadvantages. This review presents an overview of the current methodologies used to identify such molecular markers. Recent developments in technology may make the monitoring of changes in patients' tumour genotypes easier in clinical practice, which may enable patients' treatment regimens to be tailored during the course of their disease, potentially leading to improved patient outcomes.
Morphological evolution, ecological diversification and climate change in rodents

Among rodents, the lineage from Progonomys hispanicus to Stephanomys documents a case of increasing size and dental specialization during an approximately 9 Myr time-interval. On the contrary, some contemporaneous generalist lineages like Apodemus show a limited morphological evolution. Dental shape can be related to diet and can be used to assess the ecological changes along the lineages. Consequently, size and shape of the first upper molar were measured in order to quantify the patterns of morphological evolution along both lineages and compare them to environmental trends. Climatic changes do not have a direct influence on evolution, but they open new ecological opportunities by changing vegetation and allow the evolution of a specialist like Stephanomys. On the other hand, environmental changes are not dramatic enough to destroy the habitat of a long-term generalist like Apodemus. Hence, our results exemplify a case of an influence of climate on the evolution of specialist species, although a generalist species may persist without change.
Time Present and Time Past.

The nature of library education depends on the larger professional environment. Professional practice creates demands for change which are reflected in library education. Many current issues in education for librarianship have received continued attention for years. This paper identifies contemporary educational concerns and challenges which were familiar to library educators in the early part of the century. Library Journal issues of 1910 and 1920 were examined to identify major professional concerns which had a curricular impact on library education: management, public service, technical service, the book sciences, and Americanization. Besides the changing curriculum, six major educational concerns are identified and discussed: the role of on the job training; specialization; practical training, certification; the leadership role of library education; and the length of entry level library education. The early literature reminds us that we have made little progress with many of these issues.
Successful Clinical Supervision of Prelicensed Counselors

ABSTRACT A comprehensive qualitative inquiry was conducted to obtain descriptive data related to perceived needs and existing practices for supervision of prelicensed, entry-level counselors. Of the 12 thematic categories that emerged in the data analysis, outcome indicators of successful supervision commanded attention of the authors. That element of the findings is discussed in this paper.
PPAR-γ/IL-10 Axis Inhibits MyD88 Expression and Ameliorates Murine Polymicrobial Sepsis

Polymicrobial sepsis induces organ failure and is accompanied by overwhelming inflammatory response and impairment of microbial killing. Peroxisome proliferator-activated receptor (PPAR)-γ is a nuclear receptor with pleiotropic effects on lipid metabolism, inflammation, and cell proliferation. The insulin-sensitizing drugs thiazolidinediones (TZDs) are specific PPAR-γ agonists. TZDs exert anti-inflammatory actions in different disease models, including polymicrobial sepsis. The TZD pioglitazone, which has been approved by the U.S. Food and Drug Administration, improves sepsis outcome; however, the molecular programs that mediate its effect have not been determined. In a murine model of sepsis, we now show that pioglitazone treatment improves microbial clearance and enhances neutrophil recruitment to the site of infection. We also observed reduced proinflammatory cytokine production and high IL-10 levels in pioglitazone-treated mice. These effects were associated with a decrease in STAT-1–dependent expression of MyD88 in vivo and in vitro. IL-10R blockage abolished PPAR-γ–mediated inhibition of MyD88 expression. These data demonstrate that the primary mechanism by which pioglitazone protects against polymicrobial sepsis is through the impairment of MyD88 responses. This appears to represent a novel regulatory program. In this regard, pioglitazone provides advantages as a therapeutic tool, because it improves different aspects of host defense during sepsis, ultimately enhancing survival.
Exchange mechanisms between ethical leadership and affective commitment

Purpose – The purpose of this paper is to examine the underlying exchange mechanisms between ethical leadership behavior and affective commitment. The authors hypothesized that ethical leadership behavior enhances perceived organizational support (POS), which then raises employee affective commitment. The authors further predicted that economic exchange weakens such indirect effect of ethical leadership on affective commitment via POS. Design/methodology/approach – Using a two-phase survey, the authors tested the hypotheses with a sample of 176 bank employees in Macau using hierarchical regression analysis and bootstrapping. Findings – POS was found to mediate the relationship between ethical leadership behavior and affective commitment, whereas economic exchange was found to moderate the ethical leadership behavior – POS relationship as well as its indirect effect on affective commitment via POS. Originality/value – By identifying POS as the mediator and economic exchange as the moderator, this study enh.
Immunogenic and Antioxidant Effects of a Pathogen-Associated Prenyl Pyrophosphate in Anopheles gambiae

Despite efficient vector transmission, Plasmodium parasites suffer great bottlenecks during their developmental stages within Anopheles mosquitoes. The outcome depends on a complex three-way interaction between host, parasite and gut bacteria. Although considerable progress has been made recently in deciphering Anopheles effector responses, little is currently known regarding the underlying microbial immune elicitors. An interesting candidate in this sense is the pathogen-derived prenyl pyrophosphate and designated phosphoantigen (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMBPP), found in Plasmodium and most eubacteria but not in higher eukaryotes. HMBPP is the most potent stimulant known of human Vγ9Vδ2 T cells, a unique lymphocyte subset that expands during several infections including malaria. In this study, we show that Vγ9Vδ2 T cells proliferate when stimulated with supernatants from intraerythrocytic stages of Plasmodium falciparum cultures, suggesting that biologically relevant doses of phosphoantigens are excreted by the parasite. Next, we used Anopheles gambiae to investigate the immune- and redox- stimulating effects of HMBPP. We demonstrate a potent activation in vitro of all but one of the signaling pathways earlier implicated in the human Vγ9Vδ2 T cell response, as p38, JNK and PI3K/Akt but not ERK were activated in the A. gambiae 4a3B cell line. Additionally, both HMBPP and the downstream endogenous metabolite isopentenyl pyrophosphate displayed antioxidant effects by promoting cellular tolerance to hydrogen peroxide challenge. When provided in the mosquito blood meal, HMBPP induced temporal changes in the expression of several immune genes. In contrast to meso-diaminopimelic acid containing peptidoglycan, HMBPP induced expression of dual oxidase and nitric oxide synthase, two key determinants of Plasmodium infection. Furthermore, temporal fluctuations in midgut bacterial numbers were observed. The multifaceted effects observed in this study indicates that HMBPP is an important elicitor in common for both Plasmodium and gut bacteria in the mosquito.
Electroencephalograms Multiscale Entropy Analysis of Alzheimer's Disease Patients

The aim of this study was to analyse the EEG background activity in Alzheimer's disease (AD) with two non-linear methods: Approximate Entropy (ApEn) and Auto Mutual Information (AMI). ApEn quantifies the regularity in data, while AMI detects linear and non-linear dependencies in time series and can be used as a normalized complexity measure. EEGs were recorded from the 19 scalp loci of the international 10-20 system in 11 AD patients and 11 age-matched controls. ApEn was significantly lower in AD patients at electrodes O1, P3 and P4 (p<0.05). The AMI of the AD patients decreased significantly more slowly with time delays than the AMI of control subjects at electrodes T5, O1, P3 and P4 (p<0.05). The decreased irregularity and complexity found in AD patients leads us to think that EEG analysis with ApEn and AMI could help to increase our insight into brain dysfunction in AD.
Occupational Interests and Aspirations of Rural Black South African Children: Considerations for Theory, Research and Practice

There has been limited international and South African research on the career development of rural and socioeconomically disadvantaged children. The present research provides baseline information on the career development of rural, low socioeconomic status, Black upper elementary school children (N = 292; 154 girls and 138 boys) in relation to their occupational interests and aspirations. Interests and aspirations were classified in terms of Holland's typology and status level. The results revealed that the children were more interested in and aspired more towards professional status level occupations in Social (i.e., people) and Investigative (i.e., scientific) type categories. Several significant gender differences were found. Girls aspired more to Social type occupations and boys more to Investigative type occupations, with the children's occupational aspirations reflecting gender traditionality. The implications of the present findings present the field with challenges in terms of career theory, research and practice
Federal Reserve Bank of Minneapolis Research Department Staff Report 436

We conduct a systematic empirical study of cross-sectional inequality in the United States, integrating data from the Current Population Survey, the Panel Study of Income Dynamics, the Consumer Expenditure Survey, and the Survey of Consumer Finances. In order to understand how different dimensions of inequality are related via choices, markets, and institutions, we follow the mapping suggested by the household budget constraint from individual wages to individual earnings, to household earnings, to disposable income, and, ultimately, to consumption and wealth. We document a continuous and sizable increase in wage inequality over the sample period. Changes in the distribution of hours worked sharpen the rise in earnings inequality before 1982, but mitigate its increase thereafter. Taxes and transfers compress the level of income inequality, especially at the bottom of the distribution, but have little effect on the overall trend. Finally, access to financial markets has limited both the level and growth of consumption inequality. and Luigi Pistaferri for detailed comments. We thank Dean Lillard for providing data on transfers for the 1994—2003 waves of the PSID. We thank the National Science Foundation (Grant SES-0418029 for Heathcote and Violante and Grant SES-0820519 for Perri). The views expressed herein are those of the authors and not necessarily those of the Federal Reserve Bank of Minneapolis or the Federal Reserve System.
Survival of patients with severe alpha 1-antitrypsin deficiency with special reference to non-index cases.

BACKGROUND--Previous estimates of the survival times of patients with alpha 1-antitrypsin deficiency have been based on selected patients. METHODS--The survival times of 397 patients with severe alpha 1-antitrypsin deficiency identified by pulmonary impairment (index cases) or through family studies (non-index cases) were compared. RESULTS--The overall median survival time was 54.5 years with no significant difference between men and women. Survival for index cases was less than for the non-index cases regardless of smoking history (49.4 years and 69.3 years respectively). When index and non-index cases were analysed separately there was no difference between the survival of smokers and never smokers in the index group. In the non-index group smokers had a shorter survival time than never smokers. The survival time of never smokers was similar to that of the normal Danish population. CONCLUSIONS--The prognosis of severe alpha 1-antitrypsin deficiency is better than previously assumed and, although smoking is a major risk factor, the development of emphysema in patients with severe alpha 1-antitrypsin deficiency is multifactorial.
On the chemistry and distribution of HOC+ in M 82 More evidence for extensive PDRs

Context. The molecular gas composition in the inner 1 kpc disk of the starburst galaxy M 82 resembles that of Galactic Photon Dominated Regions (PDRs). In particular, large abundances of the reactive ions HOC + and CO + have been measured in the nucleus of this galaxy. Two explanations have been proposed for such high abundances: the influence of intense UV fields from massive stars, or a significant role of X-Rays. Aims. Our aim is to investigate the origin of the high abundances of reactive ions in M 82. Methods. We have completed our previous 30 m HOC + J = 1 → 0 observations with the higher excitation HCO + and HOC + J = 4 → 3a nd 3→ 2 rotational lines. In addition, we have obtained with the IRAM Plateau de Bure Interferometer (PdBI) a 4 �� resolution map of the HOC + emission in M 82, the first ever obtained in a Galactic or extragalactic source. Results. Our HOC + interferometric image shows that the emission of the HOC + 1 → 0 line is mainly restricted to the nuclear disk, with the maxima towards the E and W molecular peaks. In addition, line excitation calculations imply that the HOC + emission arises in dense gas (n ≥ 10 4 cm −3 ). Therefore, the HOC + emission is arising in the dense PDRs embedded in the M 82 nuclear disk, rather than in the intercloud phase and/or wind. Conclusions. We have improved our previous chemical model of M 82 by (i) using the new version of the Meudon PDR code; (ii) updating the chemical network; and (iii) considering two different types of clouds (with different thickness) irradiated by the intense interstellar UV field (G0 = 10 4 in units of the Habing field) prevailing in the nucleus of M 82. Most molecular observations (HCO + , HOC + ,C O + , CN, HCN, H3O + ) are well explained assuming that ∼87% of the mass of the molecular gas is forming small clouds (Av = 5 mag) while only ∼13% of the mass is in large molecular clouds (Av = 50 mag). Such a small number of large molecular clouds suggests that M 82 is an old starburst, where star formation has almost exhausted the molecular gas reservoir.
Control design of robot for compliant manipulation on dynamic environments

The problem of control design of robot performing compliant manipulation is addressed. Compliant manipulation fundamentally requires that the controlled robot not only follow up the input trajectory exactly in free motion space, but also manipulate adaptively on dynamic environments while making compliant contact with its dynamic constrained space. A model-matching approach for the control design of robot manipulators is presented. The problems of how to select the reference model according to environment dynamics (while considering its dynamic uncertainty, the contact discontinuity, and the robot actuator's output limitation) and how to implement such a reference model in a robot control system are analyzed. The effectiveness of this approach is illustrated by computer simulation and experimental results compared with impedance control approach. <<ETX>>
In Vivo Evidence for Tibial Plateau Slope as a Risk Factor for Anterior Cruciate Ligament Injury

Background: In vivo studies reporting tibial plateau slope as a risk factor for anterior cruciate ligament (ACL) injury have been published with greatly increasing frequency. Purpose: To examine and summarize the in vivo evidence comparing tibial slope in ACL-injured and uninjured populations. Study Design: Systematic review and meta-analysis. Methods: We reviewed publications in Scopus, SPORTDiscus, CINAHL, and PubMed to identify all studies reporting a measure of tibial plateau slope between ACL-injured groups and controls. A meta-analysis was performed including calculation of effect size and 95% confidence interval as well as 95% confidence intervals for the mean values of the measurement in each study. Results: Fourteen studies met our inclusion/exclusion criteria. Five of 6 radiographic studies reporting medial tibial plateau slope (MTPS) demonstrated significant differences between controls and ACL-injured groups, while only 1 of 7 magnetic resonance imaging (MRI) studies reported significant differences between groups. Mean MTPS measurements and standard deviations reported for controls ranged from 2.9° ± 2.8° anterior to 9.5° ± 3° posterior. For ACL-injured patients, MTPS ranged from 1.8° ± 3.5° anterior to 12.1° ± 3.3° posterior. Lateral tibial plateau slope (LTPS) was reported to be significantly greater in ACL-injured groups in all 5 MRI-based studies reporting group comparisons. Mean values for LTPS in controls ranged from 0.3° ± 3.6° anterior slope to 9° ± 4° posterior slope. In ACL-injured groups, mean reported LTPS values ranged from 1.8° ± 3.2° to 11.5° ± 3.54° posterior slope. Conclusion: Despite high measures of reliability for the various methods reported in current studies, there is vast disagreement regarding the actual values of the slope that would be considered “at risk. ” Reported tibial slope values for control groups vary greatly between studies. In many cases, the study-to-study differences in “normal” tibial slope exceed the difference between controls and ACL-injured patients. The clinical utility of imaging-based measurement methods for the determination of ACL injury risk requires more reliable techniques that demonstrate consistency between studies.
Consistent sets of atmospheric lifetimes and radiative forcings on climate for CFC replacements: HCFCs and HFCs

Recognition of deleterious effects of chlorine and bromine on ozone and climate over the last several decades has resulted in international accords to halt the production of chlorine-containing chlorofluorocarbons (CFCs) and bromine-containing halons. It is well recognized, however, that these chemicals have had important uses to society, particularly as refrigerants, as solvents, as plastic blowing agents, as fire retardants and as aerosol propellants. This has led to an extensive search for substitute chemicals with appropriate properties to be used in place of the CFCs and halons. The purpose of this study is to evaluate in a consistent manner the atmospheric lifetime and radiative forcing on climate for a number of replacement compounds. The unique aspect of this study is its attempt to resolve inconsistencies in previous evaluations of atmospheric lifetimes and radiative forcings for these compounds by adopting a uniform approach. Using the latest version of our two-dimensional chemical-radiative-transport model of the global atmosphere, we have determined the atmospheric lifetimes of 28 hydrohalocarbons (HCFCs and HFCs). Through the comparison of the model-calculated lifetimes with lifetimes derived using a simple scaling method, our study adds to earlier findings that consideration of stratospheric losses is important in determining the lifetimes of gases. Discrepancies were found in the reported lifetimes of several replacement compounds reported in the international assessment of stratospheric ozone published by the World Meteorological Organization [Granier et al., 1999] and have been resolved. We have also derived the adjusted and instantaneous radiative forcings for CFC-11 and 20 other halocarbons using our radiative transfer model. The sensitivity of radiative forcings to the vertical distribution of these gases is investigated in this study and is shown to be significant. The difference in the global radiative forcing arising from the assumption of a constant vertical profile for these gases is found to range from 0 to 36%, with higher difference for short-lived gases. Global Warming Potentials (GWPs) for the compounds are determined using the lifetimes and radiative forcings evaluated in this study and are found to differ from values reported by Granier et al. [1999] owing to the differences in our calculated radiative forcings and lifetimes.
Negotiating the status of women’s football in Norway. An analysis of online supporter discourses

Abstract Whilst women’s football in Norway has enjoyed sporting success, media interest is still limited. It attracts few spectators and TV viewers. In this article, we analyse how online supporters of men’s football view and discuss the status of women’s football. This is done through a discourse analysis based on the conceptual framework of feminist theory. An electronic discussion group on football serves as the source of data. Two main discourses are identified: The dominant discourse associates football to “masculine” standards and core masculine values, and women’s football represents a threat to this perspective. Women’s football is “othered” by a continuous comparison to men’s football as well as by strategies of trivialisation and sexualisation. The counter-discourse emphasises women’s right to play football on equal terms with men and argues that women’s football should be assessed on its own terms. The counter-discourse opposes the arguments of the dominant discourse by challenging the taken for granted-assumptions as well as the dominant derogatory notions of women’s football. But all in all, most discussants construct women’s football as a sport trapped in a vicious circle, which deserves its current lack of recognition.