Enhanced anti-tumor effect of a gene gun-delivered DNA vaccine encoding the human papillomavirus type 16 oncoproteins genetically fused to the herpes simplex virus glycoprotein D

Anti-cancer DNA vaccines have attracted growing interest as a simple and non-invasive method for both the treatment and prevention of tumors induced by human papillomaviruses. Nonetheless, the low immunogenicity of parenterally administered vaccines, particularly regarding the activation of cytotoxic CD8+ T cell responses, suggests that further improvements in both vaccine composition and administration routes are still required. In the present study, we report the immune responses and anti-tumor effects of a DNA vaccine (pgD-E7E6E5) expressing three proteins (E7, E6, and E5) of the human papillomavirus type 16 genetically fused to the glycoprotein D of the human herpes simplex virus type 1, which was administered to mice by the intradermal (id) route using a gene gun. A single id dose of pgD-E7E6E5 (2 µg/dose) induced a strong activation of E7-specific interferon-γ (INF-γ)-producing CD8+ T cells and full prophylactic anti-tumor effects in the vaccinated mice. Three vaccine doses inhibited tumor growth in 70% of the mice with established tumors. In addition, a single vaccine dose consisting of the co-administration of pgD-E7E6E5 and the vector encoding interleukin-12 or granulocyte-macrophage colony-stimulating factor further enhanced the therapeutic anti-tumor effects and conferred protection to 60 and 50% of the vaccinated mice, respectively. In conclusion, id administration of pgD-E7E6E5 significantly enhanced the immunogenicity and anti-tumor effects of the DNA vaccine, representing a promising administration route for future clinical trials.

Attentional bias modulation by reappraisal in patients with generalized anxiety disorder: an event-related potential study

Affective states influence subsequent attention allocation. We evaluated emotional negativity bias modulation by reappraisal in patients with generalized anxiety disorder (GAD) relative to normal controls. Event-related potential (ERP) recordings were obtained, and changes in P200 and P300 amplitudes in response to negative or neutral words were noted after decreasing negative emotion or establishing a neutral condition. We found that in GAD patients only, the mean P200 amplitude after negative word presentation was much higher than after the presentation of neutral words. In normal controls, after downregulation of negative emotion, the mean P300 amplitude in response to negative words was much lower than after neutral words, and this was significant in both the left and right regions. In GAD patients, the negative bias remained prominent and was not affected by reappraisal at the early stage. Reappraisal was observed to have a lateralized effect at the late stage.

A combination of STI571 and BCR-ABL1 siRNA with overexpressed p15INK4B induced enhanced proliferation inhibition and apoptosis in chronic myeloid leukemia

p15INK4B, a cyclin-dependent kinase inhibitor, has been recognized as a tumor suppressor. Loss of or methylation of the p15INK4B gene in chronic myeloid leukemia (CML) cells enhances myeloid progenitor formation from common myeloid progenitors. Therefore, we examined the effects of overexpressed p15INK4B on proliferation and apoptosis of CML cells. Overexpression of p15INK4B inhibited the growth of K562 cells by downregulation of cyclin-dependent kinase 4 (CDK4) and cyclin D1 expression. Overexpression of p15INK4B also induced apoptosis of K562 cells by upregulating Bax expression and downregulating Bcl-2 expression. Overexpression of p15INK4B together with STI571 (imatinib) or BCR-ABL1 small interfering RNA (siRNA) also enhanced growth inhibition and apoptosis induction of K562 cells. The enhanced effect was also mediated by reduction of cyclin D1 and CDK4 and regulation of Bax and Bcl-2. In conclusion, our study may provide new insights into the role of p15INK4B in CML and a potential therapeutic target for overcoming tyrosine kinase inhibitor resistance in CML.

Enhanced production and organic solvent stability of a protease fromBrevibacillus laterosporus strain PAP04

A bacterial strain (PAP04) isolated from cattle farm soil was shown to produce an extracellular, solvent-stable protease. Sequence analysis using 16S rRNA showed that this strain was highly homologous (99%) to Brevibacillus laterosporus. Growth conditions that optimize protease production in this strain were determined as maltose (carbon source), skim milk (nitrogen source), pH 7.0, 40°C temperature, and 48 h incubation. Overall, conditions were optimized to yield a 5.91-fold higher production of protease compared to standard conditions. Furthermore, the stability of the enzyme in organic solvents was assessed by incubation for 2 weeks in solutions containing 50% concentration of various organic solvents. The enzyme retained activity in all tested solvents except ethanol; however, the protease activity was stimulated in benzene (74%) followed by acetone (63%) and chloroform (54.8%). In addition, the plate assay and zymography results also confirmed the stability of the PAP04 protease in various organic solvents. The organic solvent stability of this protease at high (50%) concentrations of solvents makes it an alternative catalyst for peptide synthesis in non-aqueous media.

Enhanced extraction of phenolic compounds from coffee industry’s residues through solid state fermentation by Penicillium purpurogenum

Abstract The use of agroindustrial residues is an economical solution to industrial biotechnology. Coffee husk and pulp are abounding residues from coffee industry which can be used as substrates in solid state fermentation process, thus allowing a liberation and increase in the phenolic compound content with high added value. By employing statistical design, initial moisture content, pH value in the medium, and the incubation temperature were evaluated, in order to increase the polyphenol content in a process of solid state fermentation by Penicillium purpurogenum. The main phenolic compounds identified through HPLC in fermented coffee residue were chlorogenic acid, caffeic acid, and rutin. Data obtained through HPLC with the radical absorbance capacity assay suggest the fermented coffee husk and pulp extracts potential as a source of phenolic acids and flavonoids. Results showed good perspectives when using P. purpurogenum strain to enhance the liberation of phenolic compounds in coffee residues.

Inflation bias: an appraisal

This short paper offers a brief appraisal of the conventional inflation bias and Cukierman's new inflation bias. It may also be seen that a lack of equilibrium in the balance of payments represents another reason for the emergence of the inflationary bias in an economy.

Gender bias in the Trends in Mathematics and Science Study 2003 (TIMMS) for Canadian students /

This study is a secondary data analysis of the Trends in Mathematics and Science Study 2003 (TIMSS) to determine if there is a gender bias, unbalanced number of items suited to the cognitive skill of one gender, and to compare performance by location. Results of the Grade 8, math portion of the test were examined. Items were coded as verbal, spatial, verbal /spatial or neither and as conventional or unconventional. A Kruskal- Wallis was completed for each category, comparing performance of students from Ontario, Quebec, and Singapore. A Factor Analysis was completed to determine if there were item categories with similar characteristics. Gender differences favouring males were found in the verbal conventional category for Canadian students and in the spatial conventional category for students in Quebec. The greatest differences were by location, as students in Singapore outperformed students from Canada in all areas except for the spatial unconventional category. Finally, whether an item is conventional or unconventional is more important than whether the item is verbal or spatial. Results show the importance of fair assessment for the genders in both the classroom and on standardized tests.

Subjective Ambivalence and the Expression of Anti-Gay Bias

Univalent attitudes toward gay people have been widely studied, but no research to date has examined ambivalent (i.e., torn, conflicted) attitudes toward gay people. However, the Justification-Suppression Model (JSM; Crandall & Eshleman, 2003) proposes that ambivalence leads to biased expressions through intrapsychic processes which facilitate biased expression, particularly in contexts presenting strong justifications for expressing prejudice and weak pressures to suppress prejudice. I test these implications in the context of bias toward gay people. In Study 1, the measurement of ambivalence is examined in terms of both subjective ambivalence (i.e., the reported experience of “torn” attitudes) and calculated ambivalence (i.e., mathematical conflict between positive and negative attitude components). I find that higher subjective ambivalence is only associated with more negative attitudes toward gay people (and not positive attitudes toward gay people), and that higher subjective ambivalence predicts less gay rights support even after taking negative and positive attitudes toward gay people into account. Further, higher subjective ambivalence is associated with ideological opposition to gay people and more negative intergroup emotions (e.g., intergroup disgust). These findings suggest it is valuable to examine the unique component of subjective ambivalence separate from univalent negativity. Because calculated ambivalence measures are mathematically dependent upon a univalent negative measure, they cannot be examined separately from negativity. Therefore, subjective ambivalence is the focus of Study 2. The main goals of Study 2 were to determine why and when subjective ambivalence is related to bias. I examined the extent to which the negative relation between subjective ambivalence and opposition to anti-gay bullying can be accounted for by lower intergroup empathy and lower collective guilt, which may facilitate the expression of bias in keeping with the JSM. The relation between subjective ambivalence and anti-gay bullying opposition was examined within four social contexts based on a 2 (high vs. low offensiveness) x 2 (normatively unjustified vs. normatively justified) manipulation. I expected that higher subjective ambivalence would be most strongly related to lower intergroup empathy and collective guilt when there are the strongest justifications for bias expression, and that lower intergroup empathy and collective guilt would lead to less opposition to anti-gay bullying. Higher subjective ambivalence predicted less anti-gay bullying opposition. After accounting for positivity and negativity, the direct effect of subjective ambivalence was no longer significant, yet subjective ambivalence uniquely predicted intergroup empathy, which in turn predicted less anti-gay bullying opposition. These findings provide evidence that subjective ambivalence is largely negative in nature, but also presents evidence for a unique component of subjective ambivalence (separate from univalent attitudes) associated with low intergroup empathy and negativity. In contrast to previous research, I found very little evidence for the context-dependency of subjective ambivalence. Further research on subjective ambivalence, including subjective ambivalence toward other social groups, may expand our understanding of the factors leading to biased expressions.

Subliminal Exposure to Empathy Primes: A New Method to Reduce Intergroup Bias?

An abundant literature has demonstrated the benefits of empathy for intergroup relations (e.g., Batson, Chang, Orr, & Rowland, 2002). In addition, empathy has been identified as the mechanism by which various successful prejudice-reduction procedures impact attitudes and behaviour (e.g., Costello & Hodson, 2010). However, standard explicit techniques used in empathy-prejudice research have a number of potential limitations (e.g., resistance; McGregor, 1993). The present project explored an alternative technique, subliminally priming (i.e., outside of awareness) empathy-relevant terms (Study 1), or empathy itself (Study 2). Study 1 compared the effects of exposure to subliminal empathy-relevant primes (e.g., compassion) versus no priming and priming the opposite of empathy (e.g., indifference) on prejudice (i.e., negative attitudes), discrimination (i.e., resource allocation), and helping behaviour (i.e., willingness to empower, directly assist, or expect group change) towards immigrants. Relative to priming the opposite of empathy, participants exposed to primes of empathy-relevant constructs expressed less prejudice and were more willingness to empower immigrants. In addition, the effects were not moderated by individual differences in prejudice-relevant variables (i.e., Disgust Sensitivity, Intergroup Disgust-Sensitivity, Intergroup Anxiety, Social Dominance Orientation, Right-wing Authoritarianism). Study 2 considered a different target category (i.e., Blacks) and attempted to strengthen the effects found by comparing the impact of subliminal empathy primes (relative to no prime or subliminal primes of empathy paired with Blacks) on explicit prejudice towards marginalized groups and Blacks, willingness to help marginalized groups and Blacks, as well as implicit prejudice towards Blacks. In addition, Study 2 considered potential mechanisms for the predicted effects; specifically, general empathy, affective empathy towards Blacks, cognitive empathy towards Blacks, positive mood, and negative mood. Unfortunately, using subliminal empathy primes “backfired”, such that exposure to subliminal empathy primes (relative to no prime) heightened prejudice towards marginalized groups and Blacks, and led to stronger expectations that marginalized groups and Blacks improve their own situation. However, exposure to subliminal primes pairing empathy with Blacks (relative to subliminal empathy primes alone) resulted in less prejudice towards marginalized groups and more willingness to directly assist Blacks, as expected. Interestingly, exposure to subliminal primes of empathy paired with Blacks (vs. empathy alone) resulted in more pro-White bias on the implicit prejudice measure. Study 2 did not find that the potential mediators measured explained the effects found. Overall, the results of the present project do not provide strong support for the use of subliminal empathy primes for improving intergroup relations. In fact, the results of Study 2 suggest that the use of subliminal empathy primes may even backfire. The implications for intergroup research on empathy and priming procedures generally are discussed.

Individual Differences in Global/Local Processing Bias and the Attentional Blink

When the second of two targets (T2) is presented temporally close to the first target (T1) in rapid serial visual presentation, accuracy to detect/identify T2 is markedly reduced as compared to longer target separations. This is known as the attentional blink (AB), and is thought to reflect a limitation of selective attention. While most individuals show an AB, research has demonstrated that individuals are variously susceptible to this effect. To explain these differences, Dale and Arnell (2010) examined whether dispositional differences in attentional breadth, as measured by the Navon letter task, could predict individual AB magnitude. They found that individuals who showed a natural bias toward the broad, global level of Navon letter stimuli were less susceptible to the AB as compared to individuals who showed a natural bias toward the detailed, local aspects of Navon letter stimuli. This suggests that individuals who naturally broaden their attention can overcome the AB. However, it was unclear how stable these individual differences were over time, and whether a variety of global/local tasks could predict AB performance. As such, the purpose of this dissertation was to investigate, through four empirical studies, the nature of individual differences in both global/local bias and the AB, and how these differences in attentional breadth can modulate AB performance. Study 1 was designed to examine the stability of dispositional global/local biases over time, as well as the relationships among three different global/local processing measures. Study 2 examined the stability of individual differences in the AB, as well as the relationship among two distinct AB tasks. Study 3 examined whether the three distinct global/local tasks used in Study 1 could predict performance on the two AB tasks from Study 2. Finally, Study 4 explored whether individual differences in global/local bias could be manipulated by exposing participants to high/low spatial frequencies and Navon stimuli. In Study 1, I showed that dispositional differences in global/local bias were reliable over a period of at least a week, demonstrating that these individual biases may be trait-like. However, the three tasks that purportedly measure global/local bias were unrelated to each other, suggesting that they measure unique aspects of global/local processing. In Study 2, I found that individual variation in AB performance was also reliable over a period of at least a week, and that the two AB task versions were correlated. Study 3 showed that dispositional global/local biases, as measured by the three tasks from Study 1, predicted AB magnitude, such that individuals who were naturally globally biased had smaller ABs. Finally, in Study 4 I demonstrated that these dispositional global/local biases are resistant to both spatial frequency and Navon letter manipulations, indicating that these differences are robust and intractable. Overall, the results of the four studies in this dissertation help clarify the role of individual differences in attentional breadth in selective attention.

The Inflation Bias When the Central Bank Targets, the Natural Rate of Unemployment

This paper studies the proposition that an inflation bias can arise in a setup where a central banker with asymmetric preferences targets the natural unemployment rate. Preferences are asymmetric in the sense that positive unemployment deviations from the natural rate are weighted more (or less) severely than negative deviations in the central banker's loss function. The bias is proportional to the conditional variance of unemployment. The time-series predictions of the model are evaluated using data from G7 countries. Econometric estimates support the prediction that the conditional variance of unemployment and the rate of inflation are positively related.