Studies on women's sexuality in China since 1980: A critical review

Over the last 20 years, women's sexuality has become one of the most written about and intensely debated subjects in sexology, sociology, and women's studies in mainland China. From these studies, one can trace the development of academic discourse on women's sexuality through three distinct phases: from a predominantly medical discourse, to the use of survey methods to investigate women's real experiences, and finally to a phase in which Western theories have become increasingly influential. Each phase features a distinct stereotype of woman. The implications of this review for sexual research in China will also be discussed.published_or_final_versio

Antiviral activities and applications of ribosomally synthesized and post-translationally modified peptides (RiPPs)

The emergence and re-emergence of viral epidemics and the risks of antiviral drug resistance are a serious threat to global public health. New options to supplement or replace currently used drugs for antiviral therapy are urgently needed. The research in the field of ribosomally synthesized and post-translationally modified peptides (RiPPs) has been booming in the last few decades, in particular in view of their strong antimicrobial activities and high stability. The RiPPs with antiviral activity, especially those against enveloped viruses, are now also gaining more interest. RiPPs have a number of advantages over small molecule drugs in terms of specificity and affinity for targets, and over protein-based drugs in terms of cellular penetrability, stability and size. Moreover, the great engineering potential of RiPPs provides an efficient way to optimize them as potent antiviral drugs candidates. These intrinsic advantages underscore the good therapeutic prospects of RiPPs in viral treatment. With the aim to highlight the underrated antiviral potential of RiPPs and explore their development as antiviral drugs, we review the current literature describing the antiviral activities and mechanisms of action of RiPPs, discussing the ongoing efforts to improve their antiviral potential and demonstrate their suitability as antiviral therapeutics. We propose that antiviral RiPPs may overcome the limits of peptide-based antiviral therapy, providing an innovative option for the treatment of viral disease

KSAT: Knowledge-infused Self Attention Transformer - Integrating Multiple Domain-Specific Contexts

Domain-specific language understanding requires integrating multiple pieces of relevant contextual information. For example, we see both suicide and depression related behavior (multiple contexts) in the text “I have a gun and feel pretty bad about my life, and it wouldn’t be the worst thing if I didn’t wake up tomorrow”. Domain specificity in self-attention architectures is handled by fine-tuning on excerpts from relevant domain specific resources (datasets and external knowledge - medical textbook chapters on mental health diagnosis related to suicide and depression). We propose a modified self-attention architecture Knowledge infused Self Attention Transformer (KSAT) that achieves the integration of multiple domain-specific contexts through the use of external knowledge sources. KSAT introduces knowledge-guided biases in dedicated self-attention layers for each knowledge source to accomplish this. In addition, KSAT provides mechanics for controlling the trade-off between learning from data and learning from knowledge. Our quantitative and qualitative evaluations show that (1) the KSAT architecture provides novel human-understandable ways to precisely measure and visualize the contributions of the infused domain contexts, and (2) KSAT performs competitively with other knowledge-infused baselines and significantly outperforms baselines that use fine-tuning for domain-specific task

PAC1 Deficiency in a Murine Model Induces Gastric Mucosa Hypertrophy and Higher Basal Gastric Acid Output

Pituitary adenylate cyclase-activating polypeptide (PACAP) has been shown to increase the histamine release from gastric enterochromaffin-like (ECL) cells and promote gastric acid secretion in rats. In contrast, in mice, PACAP has been demonstrated to induce a decrease of gastric acid secretion, an effect presumably due to somatostatin release. To more clearly define the role of PACAP in the regulation of gastric acid output, a knockout mouse model for the PACAP-specific receptor PAC1 was applied in this study. Measurements of the basal and stimulated gastric acid secretion and morphological studies on the gastric mucosa were performed in both wild-type and PAC1-deficient mice. Compared with the wild-type mice, the PAC1-deficient mice showed a nearly threefold higher basal gastric acid output, increased gastric mucosa thickness and glands height, and proportional increases in parietal and total cell counts in the gastric mucosa. The PAC1-deficient mice also showed a trend of increased plasma gastrin levels and gastrin gene expression in the gastric mucosa. This study indicates that the expression of PAC1 is clearly important for maintaining the homeostasis of gastric acid secretion. Loss of PACAP receptor during development may lead to a compensatory mechanism regulating gastric acid secretion

Infection-generated electric field in gut epithelium drives bidirectional migration of macrophages.

Many bacterial pathogens hijack macrophages to egress from the port of entry to the lymphatic drainage and/or bloodstream, causing dissemination of life-threatening infections. However, the underlying mechanisms are not well understood. Here, we report that Salmonella infection generates directional electric fields (EFs) in the follicle-associated epithelium of mouse cecum. In vitro application of an EF, mimicking the infection-generated electric field (IGEF), induces directional migration of primary mouse macrophages to the anode, which is reversed to the cathode upon Salmonella infection. This infection-dependent directional switch is independent of the Salmonella pathogenicity island 1 (SPI-1) type III secretion system. The switch is accompanied by a reduction of sialic acids on glycosylated surface components during phagocytosis of bacteria, which is absent in macrophages challenged by microspheres. Moreover, enzymatic cleavage of terminally exposed sialic acids reduces macrophage surface negativity and severely impairs directional migration of macrophages in response to an EF. Based on these findings, we propose that macrophages are attracted to the site of infection by a combination of chemotaxis and galvanotaxis; after phagocytosis of bacteria, surface electrical properties of the macrophage change, and galvanotaxis directs the cells away from the site of infection

High-throughput screening for substrate specificity-adapted mutants of the nisin dehydratase NisB

Microbial lanthipeptides are formed by a two-step enzymatic introduction of (methyl)lanthionine rings. A dehydratase catalyzes the dehydration of serine and threonine residues, yielding dehydroalanine and dehydrobutyrine, respectively. Cyclase-catalyzed coupling of the formed dehydroresidues to cysteines forms (methyl)lanthionine rings in a peptide. Lanthipeptide biosynthetic systems allow discovery of target-specific, lanthionine-stabilized therapeutic peptides. However, the substrate specificity of existing modification enzymes impose limitations on installing lanthionines in non-natural substrates. The goal of the present study was to obtain a lanthipeptide dehydratase with the capacity to dehydrate substrates that are unsuitable for the nisin dehydratase NisB. We report high-throughput screening for tailored specificity of intracellular, genetically encoded NisB dehydratases. The principle is based on the screening of bacterially displayed lanthionine-constrained streptavidin ligands, which have a much higher affinity for streptavidin than linear ligands. The designed NisC-cyclizable high-affinity ligands can be formed via mutant NisB-catalyzed dehydration but less effectively via wild-type NisB activity. In Lactococcus lactis, a cell surface display precursor was designed comprising DSHPQFC. The Asp residue preceding the serine in this sequence disfavors its dehydration by wild-type NisB. The cell surface display vector was coexpressed with a mutant NisB library and NisTC. Subsequently, mutant NisB-containing bacteria that display cyclized strep ligands on the cell surface were selected via panning rounds with streptavidin-coupled magnetic beads. In this way, a NisB variant with a tailored capacity of dehydration was obtained, which was further evaluated with respect to its capacity to dehydrate nisin mutants. These results demonstrate a powerful method for selecting lanthipeptide modification enzymes with adapted substrate specificity

Stratified Trajectories: Charting Equity Gaps in Program Pathways Among Community College Students

A primary focus among colleges implementing student success reforms has been to increase overall rates of credential completion and to reduce racial and socioeconomic equity gaps in completion rates. The focus on general completion may overlook inequities in the type of program students complete, which is particularly significant given the wide variety of credentials offered at community colleges—from short-term certificates to transfer-oriented associate degrees that may lead to bachelor’s and graduate degree programs—and the resulting variation in labor market returns among completers. This study examines racial/ethnic stratification among community college students as they enter and progress through different programs leading to higher- and lower-paying jobs. The authors develop a discrete-time survival analysis using longitudinal enrollment and transcript data on first-time-in-college, credential-seeking community college students from a state with more than 20 community colleges. They track student enrollment, completion, and transfer for up to nine years and examine when equity gaps in completion emerge. They also measure the student achievement of academic milestones (such as levels of credit accrual) along educational pathways that are associated with higher rates of credential completion and transfer over the long term. Results suggest that a significant gap in the likelihood of bachelor’s degree completion between Black and White students emerges more episodically, while the gap between Hispanic and White students develops earlier and remains more consistent over time. Results also suggest that while all students generally benefit from the attainment of academic milestones, such as gaining credit momentum or completing pre-transfer associate degrees, doing so disproportionately benefits Black and Hispanic students

Exhaustive and Efficient Constraint Propagation: A Semi-Supervised Learning Perspective and Its Applications

This paper presents a novel pairwise constraint propagation approach by decomposing the challenging constraint propagation problem into a set of independent semi-supervised learning subproblems which can be solved in quadratic time using label propagation based on k-nearest neighbor graphs. Considering that this time cost is proportional to the number of all possible pairwise constraints, our approach actually provides an efficient solution for exhaustively propagating pairwise constraints throughout the entire dataset. The resulting exhaustive set of propagated pairwise constraints are further used to adjust the similarity matrix for constrained spectral clustering. Other than the traditional constraint propagation on single-source data, our approach is also extended to more challenging constraint propagation on multi-source data where each pairwise constraint is defined over a pair of data points from different sources. This multi-source constraint propagation has an important application to cross-modal multimedia retrieval. Extensive results have shown the superior performance of our approach.Comment: The short version of this paper appears as oral paper in ECCV 201