How non-epistemic values can be epistemically beneficial in scientific classification

The boundaries of social categories are frequently altered to serve normative projects, such as social reform. Griffiths and Khalidi argue that the value-driven modification of categories diminishes the epistemic value of social categories. I argue that concerns over value-modified categories stem from problematic assumptions of the value-free ideal of science. Contrary to those concerns, non-epistemic value considerations can contribute to the epistemic improvement of a scientific category. For example, the early history of the category infantile autism shows how non-epistemic value considerations can contribute to delimiting and establishing infantile autism as a distinct category in mainstream psychiatry. In the case of infantile autism, non-epistemic considerations have led to a new interpretation of existing data, the expansion of research to include biology, and the creation of diagnostic criteria that further contribute to collecting relevant data. Given this case study, it can be argued that non-epistemic values can improve our knowledge of scientific categories

Impact of Macro-economic Factors on the Hemline Cycles

This current study is to investigate whether the relationships between hemline and macro-economic factors – rGDP, recession, and unemployment – are applicable now; and to analyze time lags reflecting economic factors on hemline index using U.S. data. The hemline theory and fashion cyclical theory were applied to propose the relationships studied

Can Morally Superior Values Produce Beneficial Outcomes in Science?

One proposed criterion for discerning legitimate value influences in science is to allow values that further justice-related social aims. According to this moral account, promoting human egalitarian values is legitimate and productive in science because of the moral superiority of those values. I argue that we can have a more general and feasible guide for science without appealing to the social aims of science. Earlier proposals that are more empirically focused (e.g., highlighting the significance of knowledge) can better achieve the intended outcomes of the moral account

The Effects of Consumers\u27 Values, Environment Self-identity, and Injunctive Norms on Enjoyment-based Intrinsic Motivation and Eco-friendly Apparel Purchasing Behavior

The aim of this study was to analyze how the individual\u27s values, environment self-identity, and descriptive norms, and injunctive norms influence enjoyment-based intrinsic motivation and eco-friendly apparel purchasing behavior. Researchers conducted a paper-based survey and a total of 353 Korean college students\u27 data were used for the analyses. The results showed that biospheric-altruistic values are positively related to environmental self-identity, but egoistic values had statistically significant influence on environmental self-identity in negative direction. Also, enjoyment-based intrinsic motivation to purchase eco-friendly apparel was strengthened by environmental self-identity and injunctive norms, while no significant influence by descriptive norms on enjoyment-based intrinsic motivation was found. The findings in this study suggest that college students with a strong environmental self-identity strengthened by biospheric-altruistic values enjoy purchasing eco-friendly apparel. In addition, injunctive norm was internalized via enjoyment-based motivation for college student to purchase eco-friendly apparel

Comprehensive Analysis of Transcription Factor-Based Molecular Subtypes and Their Correlation to Clinical Outcomes in Small-Cell Lung Cancer

BACKGROUND: Recent studies have reported the predictive and prognostic value of novel transcriptional factor-based molecular subtypes in small-cell lung cancer (SCLC). We conducted an in-depth analysis pairing multi-omics data with immunohistochemistry (IHC) to elucidate the underlying characteristics associated with differences in clinical outcomes between subtypes. METHODS: IHC (n = 252), target exome sequencing (n = 422), and whole transcriptome sequencing (WTS, n = 189) data generated from 427 patients (86.4% males, 13.6% females) with SCLC were comprehensively analysed. The differences in the mutation profile, gene expression profile, and inflammed signatures were analysed according to the IHC-based molecular subtype. FINDINGS: IHC-based molecular subtyping, comprised of 90 limited-disease (35.7%) and 162 extensive-disease (64.3%), revealed a high incidence of ASCL1 subtype (IHC-A, 56.3%) followed by ASCL1/NEUROD1 co-expressed (IHC-AN, 17.9%), NEUROD1 (IHC-N, 12.3%), POU2F3 (IHC-P, 9.1%), triple-negative (IHC-TN, 4.4%) subtypes. IHC-based subtype showing high concordance with WTS-based subtyping and non-negative matrix factorization (NMF) clusterization method. IHC-AN subtype resembled IHC-A (rather than IHC-N) in terms of both gene expression profiles and clinical outcomes. Favourable median overall survival was observed in IHC-A (15.2 months) compared to IHC-N (8.0 months, adjusted HR 2.3, 95% CI 1.4-3.9, p = 0.002) and IHC-P (8.3 months, adjusted HR 1.7, 95% CI 0.9-3.2, p = 0.076). Inflamed tumours made up 25% of cases (including 53% of IHC-P, 26% of IHC-A, 17% of IHC-AN, but only 11% of IHC-N). Consistent with recent findings, inflamed tumours were more likely to benefit from first-line immunotherapy treatment than non-inflamed phenotype (p = 0.002). INTERPRETATION: This study provides fundamental data, including the incidence and basic demographics of molecular subtypes of SCLC using both IHC and WTS from a comparably large, real-world Asian/non-Western patient cohort, showing high concordance with the previous NMF-based SCLC model. In addition, we revealed underlying biological pathway activities, immunogenicity, and treatment outcomes based on molecular subtype, possibly related to the difference in clinical outcomes, including immunotherapy response

Estrogen mediates inflammatory role of mast cells in endometriosis pathophysiology

Endometriosis is an estrogen dependent, chronic inflammatory disease characterized by the growth of endometrial lining outside of the uterus. Mast cells have emerged as key players in regulating not only allergic responses but also other mechanisms such as angiogenesis, fibrosis, and pain. The influence of estrogen on mast cell function has also been recognized as a potential factor driving disease pathophysiology in number of allergic and chronic inflammatory conditions. However, precise information is lacking on the cross talk between endocrine and immune factors within the endometriotic lesions and whether that contributes to the involvement of mast cells with disease pathophysiology. In this study, we observed a significant increase in mast cell numbers within endometriotic lesions compared to matched eutopic endometrium from the same patients. Compared to eutopic endometrium, endometriotic lesions had significantly higher levels of stem cell factor (SCF), a potent growth factor critical for mast cell expansion, differentiation, and survival for tissue resident mast cells. Targeted mRNA Q-PCR array revealed that the endometriotic lesions harbour microenvironment (upregulation of CPA3, VCAM1, CCL2, CMA1, CCR1, and KITLG) that is conducive to mast cells recruitment and subsequent differentiation. To examine cross-talk of mast cells within the endometriotic lesion microenvironment, endometriotic epithelial cells (12Z) and endometrial stromal cells (hESC) incubated with mast cell-conditioned media showed significantly increased production of pro-inflammatory and chemokinetic cytokines. To further understand the impact of estrogen on mast cells in endometriosis, we induced endometriosis in C57BL/6 mice. Mature mast cells were significantly higher in peritoneal fluid of estrogen-treated mice compared to untreated mice within the sham operated groups. Mouse endometriotic lesion tissue revealed several genes (qRT-PCR) relevant in mast cell biology significantly upregulated in the estrogen treated, endometriosis-induced group compared to control endometrium. The endometriotic lesions from estrogen treated mice also had significantly higher density of Alcian blue stained mast cells compared to untreated lesions or control endometrium. Collectively, these findings suggest that endometriotic lesions provide a microenvironment necessary for recruitment and differentiation of mast cells. In turn, mast cells potentially release pro-inflammatory mediators that contribute to chronic pelvic pain and endometriosis disease progression

Discovery of Q203, a potent clinical candidate for the treatment of tuberculosis

New therapeutic strategies are needed to combat the tuberculosis pandemic and the spread of multidrug-resistant (MDR) and extensively drug-resistant (XDR) forms of the disease, which remain a serious public health challenge worldwide1, 2. The most urgent clinical need is to discover potent agents capable of reducing the duration of MDR and XDR tuberculosis therapy with a success rate comparable to that of current therapies for drug-susceptible tuberculosis. The last decade has seen the discovery of new agent classes for the management of tuberculosis3, 4, 5, several of which are currently in clinical trials6, 7, 8. However, given the high attrition rate of drug candidates during clinical development and the emergence of drug resistance, the discovery of additional clinical candidates is clearly needed. Here, we report on a promising class of imidazopyridine amide (IPA) compounds that block Mycobacterium tuberculosis growth by targeting the respiratory cytochrome bc1 complex. The optimized IPA compound Q203 inhibited the growth of MDR and XDR M. tuberculosis clinical isolates in culture broth medium in the low nanomolar range and was efficacious in a mouse model of tuberculosis at a dose less than 1 mg per kg body weight, which highlights the potency of this compound. In addition, Q203 displays pharmacokinetic and safety profiles compatible with once-daily dosing. Together, our data indicate that Q203 is a promising new clinical candidate for the treatment of tuberculosis

25th annual computational neuroscience meeting: CNS-2016

The same neuron may play different functional roles in the neural circuits to which it belongs. For example, neurons in the Tritonia pedal ganglia may participate in variable phases of the swim motor rhythms [1]. While such neuronal functional variability is likely to play a major role the delivery of the functionality of neural systems, it is difficult to study it in most nervous systems. We work on the pyloric rhythm network of the crustacean stomatogastric ganglion (STG) [2]. Typically network models of the STG treat neurons of the same functional type as a single model neuron (e.g. PD neurons), assuming the same conductance parameters for these neurons and implying their synchronous firing [3, 4]. However, simultaneous recording of PD neurons shows differences between the timings of spikes of these neurons. This may indicate functional variability of these neurons. Here we modelled separately the two PD neurons of the STG in a multi-neuron model of the pyloric network. Our neuron models comply with known correlations between conductance parameters of ionic currents. Our results reproduce the experimental finding of increasing spike time distance between spikes originating from the two model PD neurons during their synchronised burst phase. The PD neuron with the larger calcium conductance generates its spikes before the other PD neuron. Larger potassium conductance values in the follower neuron imply longer delays between spikes, see Fig. 17.Neuromodulators change the conductance parameters of neurons and maintain the ratios of these parameters [5]. Our results show that such changes may shift the individual contribution of two PD neurons to the PD-phase of the pyloric rhythm altering their functionality within this rhythm. Our work paves the way towards an accessible experimental and computational framework for the analysis of the mechanisms and impact of functional variability of neurons within the neural circuits to which they belong

Another creed no one ever taught them: re-visioning theological ideas for women in Charlotte Brontë's novels

Doctor of Philosophy in English, North-West University, Potchefstroom CampusThis dissertation examines the redefinition of Victorian women’s creed and quest for selffulfilment based on their Protestant faith in three selected texts by Charlotte Brontë, namely Jane Eyre (1847), Shirley (1849), and Villette (1853). This involves the interrogation of Brontë’s representation of her female protagonists’ subversion of the discriminatory theological ideologies and practices of patriarchal Christianity during the Victorian era. The core aim of this dissertation was to debunk the widespread misconception of Brontë’s fiction as anti-Christian. Therefore, the argument in this thesis is that, although Brontë has been labelled an anti-Christian writer who opposes Christianity, my analyses of her novels reveal that Brontë distinguishes between patriarchal ideologies and the Christian creed. It also evinces that her criticisms are directed not at Christianity in its entirety, but specifically at the patriarchal and misogynistic theological principles that subjugated women within the religious spheres of the Victorian society. Therefore, rather than labelling Brontë’s subversiveness as anti-Christian, my argument in this thesis is that it is more logical to understand that her defiant stance was propelled by an innate zeal to instigate feminist reform–one which would liberate women who have been forced into a subordinate pre-Reformational position under patriarchal Christianity. By imbuing her female characters with a burning passion for transformation, Brontë engages in her own Reformation and seeks religious autonomy for herself and her female characters. To achieve its aim, the research employs Taylor's secularisation theory as a theoretical framework to gain an in-depth understanding of Brontë's work. Since Taylor’s secularisation theory is instrumental to the comprehension of changes in the condition of belief, it is suited to the unravelling of the process through which women, who had been excluded from the new social imaginary since the Reformation, consequently became determined to redefine their own beliefs and creed. This study establishes that, despite the exclusion of women from the pulpit and theological discourse in the Victorian era, Brontë boldly expresses her theological ideas for women through the female characters in her novels. Based on her Protestant faith, Brontë demonstrates the process of her female protagonist’s quest for her vocation with independent religious conviction in Jane Eyre. As an extension of this aspiration, in Shirley, she redefines existing theological and patriarchal ideas foisted on Victorian women who have been excluded from theology and the pulpit through the audaciousness of her female protagonists, Shirley and Caroline. Similarly, instead of adhering stoically to the prevailing misogynistic hermeneutics, she reinscribes new hermeneutics that affirm women’s religious autonomy and social participation. By creating a new imagination of Eve as the mighty mother figure, she demystifies the myth of Eve as the source of iv original sin. Through this re-envisioning of the image of Adam’s counterpart and the remodelling of the relationship between God and humans through the metaphor of the groom Messiah and his beloved bride, Brontë subverts the patriarchal quality of the Father/son model. In Villette, she further proposes her own creed, which differs from that of secularised Christianity. She cautions against the development of the Protestant faith, which affirms everyday life into an exclusive humanism that leads to the pursuit of human flourishing only. On the contrary, she presents a creed that affirms the transcendent world. Consequently, this thesis concludes that, despite the disparaging criticisms against Charlotte Brontë for her dissenting feminist vision, her authorial excellence proves that women’s quest for spiritual autonomy and self-fulfilment in ordinary life are not mutually exclusive.Doctora