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The debate about the characteristics and advantages of quantitative and qualitative methods is decades old. In their seminal monograph, "A Tale of Two Cultures" (2012, ATTC), Gary Goertz and James Mahoney argue that methods and research design practices for causal inference can be distinguished as two cultures that systematically differ from each other along 25 specific characteristics. ATTC's stated goal is a description of empirical patterns in quantitative and qualitative research. Yet, it does not include a systematic empirical evaluation as to whether the 25 are relevant and valid descriptors of applied research. In this paper, we derive five observable implications from ATTC and test the implications against a stratified random sample of 90 qualitative and 90 quantitative articles published in six journals between 1990-2012. Our analysis provides little support for the two-cultures hypothesis. Quantitative methods are largely implemented as described in ATTC, whereas qualitative methods are much more diverse than ATTC suggests. While some practices do indeed conform to the qualitative culture, many others are implemented in a manner that ATTC characterizes as constitutive of the quantitative culture. We find very little evidence for ATTC's anchoring of qualitative research with set-theoretic approaches to empirical social science research. The set-theoretic template only applies to a fraction of the qualitative research that we reviewed, with the majority of qualitative work incorporating different method choices.

Abstract The equilibrium of sex ratios in sexually reproducing species is often disrupted by various environmental and genetic factors, including endosymbionts like Wolbachia. In this study, we explore the highly female‐biased sex ratio observed in the flea beetle, Altica lythri, and its underlying mechanisms. Ancient hybridization events between Altica species have led to mitochondrial DNA introgression, resulting in distinct mitochondrial haplotypes that go along with different Wolbachia infections (HT1‐wLytA1, HT1*‐ uninfected, HT2‐wLytA2, and HT3‐wLytB). Notably, beetles with some haplotypes exclusively produce female offspring, suggesting potential Wolbachia‐induced phenomena such as feminization of genetic males. However, the observed female bias could also be a consequence of the ancient hybridization resulting in nuclear–cytoplasmic conflicts between introgressed mtDNA and nuclear genes. Through transcriptomic analysis and the program SEX‐DETector, we established markers for genotypic sex differentiation for A. lythri, enabling genetic sexing via qPCR. Our findings suggest that feminization of genetic males is contributing to the skewed sex ratios, highlighting the intricate dynamics of sex determination and reproductive strategies in this flea beetle. This study provides valuable insights into the dynamics of genetic conflicts, endosymbionts, and sex ratios, revealing the novel phenomenon of genetic male feminization in the flea beetle A. lythri.

Highlights A stable Zn anode was obtained by patterning Zn foil surfaces and endowing a zincphilic interface in microchannels. The accumulation of electrons in the microchannel and the zincphilic interface promoted preferential heteroepitaxial Zn deposition in the microchannel region and subsequent homoepitaxial Zn deposition on the array surface. The Zn symmetrical cells could undergo repeated plating/stripping for more than 25,000 cycles at the current densities of 10 and 20 mA cm−2.

This work focuses on a very narrow region in the quaternary system Na2O-P2O5-SiO2-ZrO2 to explore the occasionally proposed deficiency in zirconium and oxygen content of Na+ super-ionic conductor (NaSICON) materials. In addition, this region is known for the formation of glass-ceramics, but a systematic study of such materials has not been carried out yet. For this purpose, 2 series of compositions were defined and synthesized: Na3.4Zr2-3x/4Si2.4-x/4P0.6+x/4O12-11x/8 and Na3.4Zr2-3x/4Si2.4+x/4P0.6+1.5x/4O12-x/16. They only differ in the silicate and phosphate content. In the first series the molar content is constant, nSi + nP = 3. The latter series allows an excess of the 2 cations to meet the composition Na3.1Zr1.55Si2.3P0.7O11 or alternatively re-written as Na3.4Zr1.7Si2.52P0.77Ol2, which was formerly regarded as a superior material to the frequently reported composition Na3Zr2Si2POl2.Several characterization techniques were applied to better understand the relationships between phase formation, processing, and properties of the obtained glass ceramics in the context of the quasi-quaternary phase diagram. The investigations gave clear evidence that a glass phase is progressively formed with increasing x. Therefore, compounds with x > 0.2 have to be regarded as glass-ceramic composites. The resulting NaSICON materials revealed a very limited Zr deficiency with charge compensation by Na ions and a non-detectable amount of oxygen vacancies verified by neutron scattering and atomistic simulations.Hence, this work is the first systematic investigation of pretended Zr-deficient NaSICON materials, which clearly show the chemistry of a 2-phase region. The 2 investigated series are directed toward a region that is orthogonal to the series Na3Zr3-ySi2PyO11.5+y/2 reported in the first part of this series of publications.

Abstract Background Diagnostic approaches like the nuclear magnetic resonance spectroscopy (NMR) based quantification of metabolites, lipoproteins, and inflammation markers has helped to identify typical alterations in the blood serum of COVID-19 patients. However, confounders such as sex, and comorbidities, which strongly influence the metabolome, were often not considered. Therefore, the aim of this NMR study was to consider sex, as well as arterial hypertension (AHT), when investigating COVID-19-positive serum samples in a large age-and sex matched cohort. Methods NMR serum data from 329 COVID-19 patients were compared with 305 healthy controls. 134 COVID-19 patients were affected by AHT. These were analyzed together with NMR data from 58 hypertensives without COVID-19. In addition to metabolite, lipoprotein, and glycoprotein data from NMR, common laboratory parameters were considered. Sex was considered in detail for all comparisons. Results Here, we show that several differences emerge from previous NMR COVID-19 studies when AHT is considered. Especially, the previously described triglyceride-rich lipoprotein profile is no longer observed in COVID-19 patients, nor an increase in ketone bodies. Further alterations are a decrease in glutamine, leucine, isoleucine, and lysine, citric acid, HDL-4 particles, and total cholesterol. Additionally, hypertensive COVID-19 patients show higher inflammatory NMR parameters than normotensive patients. Conclusions We present a more precise picture of COVID-19 blood serum parameters. Accordingly, considering sex and comorbidities should be included in future metabolomics studies for improved and refined patient stratification. Due to metabolic similarities with other viral infections, these results can be applied to other respiratory diseases in the future.

Abstract Spatial transcriptomics of histological sections have revolutionized research in life sciences and enabled unprecedented insights into genetic processes involved in tissue reorganization. However, in contrast to genomic analysis, the actual biomolecular composition of the sample has fallen behind, leaving a gap of potentially highly valuable information. Raman microspectroscopy provides untargeted spatiomolecular information at high resolution, capable of filling this gap. In this study we demonstrate spatially resolved Raman “spectromics” to reveal homogeneity, heterogeneity and dynamics of cell matrix on molecular levels by repurposing state-of-the-art bioinformatic analysis tools commonly used for transcriptomic analyses. By exploring sections of murine myocardial infarction and cardiac hypertrophy, we identify myocardial subclusters when spatially approaching the pathology, and define the surrounding metabolic and cellular (immune-) landscape. Our innovative, label-free, non-invasive “spectromics” approach could therefore open perspectives for a profound characterization of histological samples, while additionally allowing the combination with consecutive downstream analyses of the very same specimen.

Abstract Background In recent years, advances in high-throughput sequencing technologies have enabled the use of genomic information in many fields, such as precision medicine, oncology, and food quality control. The amount of genomic data being generated is growing rapidly and is expected to soon surpass the amount of video data. The majority of sequencing experiments, such as genome-wide association studies, have the goal of identifying variations in the gene sequence to better understand phenotypic variations. We present a novel approach for compressing gene sequence variations with random access capability: the Genomic Variant Codec (GVC). We use techniques such as binarization, joint row- and column-wise sorting of blocks of variations, as well as the image compression standard JBIG for efficient entropy coding. Results Our results show that GVC provides the best trade-off between compression and random access compared to the state of the art: it reduces the genotype information size from 758 GiB down to 890 MiB on the publicly available 1000 Genomes Project (phase 3) data, which is 21% less than the state of the art in random-access capable methods. Conclusions By providing the best results in terms of combined random access and compression, GVC facilitates the efficient storage of large collections of gene sequence variations. In particular, the random access capability of GVC enables seamless remote data access and application integration. The software is open source and available at https://github.com/sXperfect/gvc/ .

STEM graduate education is vitally important in producing the talent needed to fuel our economy and provide solutions for the challenges we face in emerging diseases and climate change. Yet recent research indicates that women and students who identify as members of minority groups traditionally underrepresented in STEM face extraordinary challenges in their graduate careers. This commentary describes ways in which chemistry graduate education could become more supportive and inclusive through changes by graduate students, faculty, departments, funding agencies, and professional organizations. As a result the scientific workforce could utilize the full range of available talent and become more productive.

Graduate training is a key element in producing a scientific workforce that reflects the nation's diversity. This paper examines data from a 2013 American Chemical Society (ACS) survey of 2,544 chemistry masters and doctoral students and reveals barriers to reaching this goal. Multivariate statistical analyses indicate that women reported significantly less supportive relationships with advisors. Women were less likely to plan to finish their degrees, and for PhD students, the discrepancy was larger for students at the start of their graduate program. Women were also less likely to pursue the next level of training, and the gender difference related to postdoctoral plans was greater for those who identified with a racial-ethnic group traditionally underrepresented in chemistry (underrepresented minority, URM). URM students who were beyond the first year of their graduate program reported significantly less supportive relationships with peers. They were also less likely to have funding sufficient to meet their needs and more often used personal resources including loans. Despite these difficulties, URM students were more likely to definitely plan to finish their degrees, and men who identified as URM were more likely to plan to pursue postdoctoral work. Independent of gender and identification as URMs, students in more highly ranked schools reported less advisor support. Extensive open-ended comments indicated that large proportions of the students desired more attention and meaningful feedback from advisors and changes within their programs to promote support for students and advisor accountability. Suggestions for future research are given, and a companion commentary discusses needed directions for change.

Theories of causation in philosophy ask what makes causal claims true and establish the so-called truth conditions allowing one to separate causal from noncausal relationships. We argue that social scientists should be aware of truth conditions of causal claims because they imply which method of causal inference can establish whether a specific claim holds true. A survey of social scientists shows that this is worth emphasizing because many respondents have unclear concepts of causation and link methods to philosophical criteria in an incoherent way. We link five major theories of causation to major small and large-n methods of causal inference to provide clear guidelines to researchers and improve dialogue across methods. While most theories can be linked to more than one method, we argue that structural counterfactual theories are most useful for the social sciences since they require neither social and natural laws nor physical processes to assess causal claims.

Explanation has been identified as an important capability for AI-based systems, but research on systematic strategies for achieving understanding in interaction with such systems is still sparse. Negation is a linguistic strategy that is often used in explanations. It creates a contrast space between the affirmed and the negated item that enriches explaining processes with additional contextual information. While negation in human speech has been shown to lead to higher processing costs and worse task performance in terms of recall or action execution when used in isolation, it can decrease processing costs when used in context. So far, it has not been considered as a guiding strategy for explanations in human-robot interaction. We conducted an empirical study to investigate the use of negation as a guiding strategy in explanatory human-robot dialogue, in which a virtual robot explains tasks and possible actions to a human explainee to solve them in terms of gestures on a touchscreen. Our results show that negation vs. affirmation 1) increases processing costs measured as reaction time and 2) increases several aspects of task performance. While there was no significant effect of negation on the number of initially correctly executed gestures, we found a significantly lower number of attempts—measured as breaks in the finger movement data before the correct gesture was carried out—when being instructed through a negation. We further found that the gestures significantly resembled the presented prototype gesture more following an instruction with a negation as opposed to an affirmation. Also, the participants rated the benefit of contrastive vs. affirmative explanations significantly higher. Repeating the instructions decreased the effects of negation, yielding similar processing costs and task performance measures for negation and affirmation after several iterations. We discuss our results with respect to possible effects of negation on linguistic processing of explanations and limitations of our study.

ABSTRACT Clostridioides difficile infections begin when its metabolically dormant spores germinate in response to sensing bile acid germinants alongside amino acid and divalent cation co-germinants in the small intestine. While bile acid germinants are essential for C. difficile spore germination, it is currently unclear whether both co-germinant signals are required. One model proposes that divalent cations, particularly Ca2+, are essential for inducing germination, while another proposes that either co-germinant class can induce germination. The former model is based on the finding that spores defective in releasing large stores of internal Ca2+ in the form of calcium dipicolinic acid (CaDPA) cannot germinate when germination is induced with bile acid germinant and amino acid co-germinant alone. However, since the reduced optical density of CaDPA-less spores makes it difficult to accurately measure their germination, we developed a novel automated, time-lapse microscopy-based germination assay to analyze CaDPA mutant germination at the single-spore level. Using this assay, we found that CaDPA mutant spores germinate in the presence of amino acid co-germinant and bile acid germinant. Higher levels of amino acid co-germinants are nevertheless required to induce CaDPA mutant spores to germinate relative to WT spores because CaDPA released by WT spores during germination can function in a feedforward loop to potentiate the germination of other spores within the population. Collectively, these data indicate that Ca2+ is not essential for inducing C. difficile spore germination because amino acid and Ca2+ co-germinant signals are sensed by parallel signaling pathways. IMPORTANCE Clostridioides difficile spore germination is essential for this major nosocomial pathogen to initiate infection. C. difficile spores germinate in response to sensing bile acid germinant signals alongside co-germinant signals. There are two classes of co-germinant signals: Ca2+ and amino acids. Prior work suggested that Ca2+ is essential for C. difficile spore germination based on bulk population analyses of germinating CaDPA mutant spores. Since these assays rely on optical density to measure spore germination and the optical density of CaDPA mutant spores is reduced relative to WT spores, this bulk assay is limited in its capacity to analyze germination. To overcome this limitation, we developed an automated image analysis pipeline to monitor C. difficile spore germination using time-lapse microscopy. With this analysis pipeline, we demonstrate that, although Ca2+ is dispensable for inducing C. difficile spore germination, CaDPA can function in a feedforward loop to potentiate the germination of neighboring spores.

When young children learn to use language, they start to use their hands in co-verbal gesturing. There are, however, considerable differences between children, and it is not completely understood what these individual differences are due to. We studied how children at 4 years of age employ speech and iconic gestures to convey meaning in different kinds of spatial event descriptions, and how this relates to their cognitive abilities. Focusing on spontaneous illustrations of actions, we applied a semantic feature (SF) analysis to characterize combinations of speech and gesture meaning and related them to the child's visual-spatial abilities or abstract/concrete reasoning abilities (measured using the standardized SON-R 2 1/2-7 test). Results show that children with higher cognitive abilities convey significantly more meaning via gesture and less solely via speech. These findings suggest that young children's use of cospeech representational gesturing is positively related to their mental representation and reasoning abilities.

In empirical research, scholars can choose between an exploratory causes-of-effects analysis, a confirmatory effects-of-causes approach, or a mechanism-of-effects analysis that can be either exploratory or confirmatory. Understanding the choice between the approaches is important for two reasons. First, the added value of each approach depends on how much is known about the phenomenon of interest at the time of the analysis. Second, because of the specializations of methods, there are benefits to a division of labor between researchers who have expertise in the application of a given method. In this preregistered study, we test two hypotheses that follow from these arguments. We theorize that exploratory research is chosen when little is known about a phenomenon and a confirmatory approach is taken when more knowledge is available. A complementary hypothesis is that quantitative researchers opt for confirmatory designs and qualitative researchers for exploration because of their academic socialization. We test the hypotheses with a survey experiment of more than 900 political scientists from the United States and Europe. The results indicate that the state of knowledge has a significant and sizeable effect on the choice of the approach. In contrast, the evidence about the effect of methods expertise is more ambivalent.

Despite recent advances in the treatment of metastatic castration-resistant prostate cancer (CRPC), treatment is inevitably hampered by the development of drug resistance. Thus, new drugs are urgently needed. We investigated the efficacy, toxicity, and mechanism of action of the marine triterpene glycoside cucumarioside A2-2 (CA2-2) using an in vitro CRPC model. CA2-2 induced a G2/M-phase cell cycle arrest in human prostate cancer PC-3 cells and caspase-dependent apoptosis executed via an intrinsic pathway. Additionally, the drug inhibited the formation and growth of CRPC cell colonies at low micromolar concentrations. A global proteome analysis performed using the 2D-PAGE technique, followed by MALDI-MS and bioinformatical evaluation, revealed alterations in the proteins involved in cellular processes such as metastatic potential, invasion, and apoptosis. Among others, the regulation of keratin 81, CrkII, IL-1β, and cathepsin B could be identified by our proteomics approach. The effects were validated on the protein level by a 2D Western blotting analysis. Our results demonstrate the promising anticancer activity of CA2-2 in a prostate cancer model and provide insights on the underlying mode of action.

ACKR3 is a critical regulator of platelet-mediated thrombosis and organ injury following ischemia/reperfusion. Platelet ACKR3 surface expression is independently associated with all-cause mortality in patients with cardiovascular diseases.