Benchmarking Robustness of Multimodal Image-Text Models under Distribution Shift

Multimodal image-text models have shown remarkable performance in the past few years. However, evaluating robustness against distribution shifts is crucial before adopting them in real-world applications. In this work, we investigate the robustness of 12 popular open-sourced image-text models under common perturbations on five tasks (image-text retrieval, visual reasoning, visual entailment, image captioning, and text-to-image generation). In particular, we propose several new multimodal robustness benchmarks by applying 17 image perturbation and 16 text perturbation techniques on top of existing datasets. We observe that multimodal models are not robust to image and text perturbations, especially to image perturbations. Among the tested perturbation methods, character-level perturbations constitute the most severe distribution shift for text, and zoom blur is the most severe shift for image data. We also introduce two new robustness metrics (\textbf{MMI} for MultiModal Impact score and \textbf{MOR} for Missing Object Rate) for proper evaluations of multimodal models. We hope our extensive study sheds light on new directions for the development of robust multimodal models. More details can be found on the project webpage: \url{https://MMRobustness.github.io}.Comment: Accepted by Journal of Data-centric Machine Learning Research (DMLR) 202

TSG-6+ Cancer-Associated Fibroblasts Modulate Myeloid Cell Responses and Impair Anti-Tumor Response to Immune Checkpoint Therapy in Pancreatic Cancer

Resistance to immune checkpoint therapy (ICT) presents a growing clinical challenge. The tumor microenvironment (TME) and its components, namely tumor-associated macrophages (TAMs) and cancer-associated fibroblasts (CAFs), play a pivotal role in ICT resistance; however, the underlying mechanisms remain under investigation. In this study, we identify expression of TNF-Stimulated Factor 6 (TSG-6) in ICT-resistant pancreatic tumors, compared to ICT-sensitive melanoma tumors, both in mouse and human. TSG-6 is expressed by CAFs within the TME, where suppressive macrophages expressing Arg1, Mafb, and Mrc1, along with TSG-6 ligand Cd44, predominate. Furthermore, TSG-6 expressing CAFs co-localize with the CD44 expressing macrophages in the TME. TSG-6 inhibition in combination with ICT improves therapy response and survival in pancreatic tumor-bearing mice by reducing macrophages expressing immunosuppressive phenotypes and increasing CD8 T cells. Overall, our findings propose TSG-6 as a therapeutic target to enhance ICT response in non-responsive tumors

Decoding the spermatogonial stem cell niche under physiological and recovery conditions in adult mice and humans

The intricate interaction between spermatogonial stem cell (SSC) and testicular niche is essential for maintaining SSC homeostasis; however, this interaction remains largely uncharacterized. In this study, to characterize the underlying signaling pathways and related paracrine factors, we delineated the intercellular interactions between SSC and niche cell in both adult mice and humans under physiological conditions and dissected the niche-derived regulation of SSC maintenance under recovery conditions, thus uncovering the essential role of C-C motif chemokine ligand 24 and insulin-like growth factor binding protein 7 in SSC maintenance. We also established the clinical relevance of specific paracrine factors in human fertility. Collectively, our work on decoding the adult SSC niche serves as a valuable reference for future studies on the aetiology, diagnosis, and treatment of male infertility.</p

Patterns and environmental controls of soil organic carbon density in Chinese shrublands

The soils of shrublands are important for organic carbon storage in terrestrial ecosystems, but geographical patterns and environmental controls of soil organic carbon (SOC) remain largely understudied compared to other terrestrial ecosystems, leaving a significant gap in our understanding of terrestrial ecosystem carbon budgets. Here, we quantified SOC density (SOCD) and its potential determinants based on a comprehensive dataset with a consistent stratified random sampling of extensive soil profiles down to the parent material or to one meter depth across 1211 sites across China. Our up-to-date estimate of SOCD in Chinese shrublands is an average of 8.36 kg m(-2), and ca. 43% of SOC is stored in the upper 20 cm relative to the one meter top soil, which is higher than estimates for shrublands globally. We also observed that SOCD was positively related to shrubland biomass and more so with belowground biomass. Furthermore, SOCD was positively related to mean annual precipitation (MAP), soil total nitrogen (N), phosphorus (P), clay and silt percent, but decreased with increasing mean annual temperature (MAT). Dark felty soils stored the highest SOCD and frigid desert soils stored the lowest. Soil total nitrogen (N), MAP, soil type, MAT, and belowground biomass, soil clay, and pH were the best predictors of total SOCD in Chinese shrublands. We concluded that Chinese shrubland soils store the lowest density of organic carbon so far recorded compared to forests and grasslands, and that the vertical distribution of SOC in Chinese shrublands was much shallower. While both climate (in particular MAP) and soil total N exerted dominant control over geographical patterns of SOCD across Chinese shrublands, soil type also played a significant role. Our study also emphasizes this key role of edaphic variables in determining the SOCD of shrublands and that they should be better incorporated into large-scale assessments of SOC dynamics. Our study extends existing work conducted in forest and grasslands and provides the most up-to-date knowledge on benchmark values for SOCD in Chinese shrublands, with important implications for predicting the fate of C stored in shrubland soils in response to climate change

Effect of Pabpc6 knockout on spermatogenesis of male mice

Objective To investigate the role of cytoplasmic poly (A) binding protein-6 (PABPC6) in spermatogenesis of male mice. Methods The Pabpc6 in C57BL/6J mice was knocked out by CRISPR/Cas9 targeting, and the Pabpc6 was identified by PCR. Three types of mice with different genotypes of Pabpc6+/+, Pabpc6+/- and Pabpc6-/- were obtained by mating and breeding. Testis was weighed;Morphological observation and sperm counting were carried out. The mRNA and protein expression levels of Pabpc6 in different tissues were detected by real-time quantitative PCR and Western blot. Immunofluorescence and hematoxylin-eosin staining were used to observe the location of the gene and the morphological changes in the convoluted spermatic tubule of testis. Results The Pabpc6 knockout mice were successfully identified. Pabpc6 was highly expressed in testicular tissue(P＜0.001). Immunofluorescence showed that Pabpc6 was mainly expressed in spermatocyte at early sperm stage. Compared with wild-type mice, knockout mice showed no significant differences in testicular shape, sperm morphology, sperm count and the morphology of convoluted spermatic ducts. Conclusions Pabpc6 is found to be highly expressed in the testis tissue of mice. Pabpc6 has no obvious effect on spermatogenesis of male mice after knockout of Pabpc6. The results indicate that the protein encoded by Pabpc6 is not necessary for spermatogenesis of mice

PEPTIDE NANOFILAMENTS USED FOR REPLICA-MOLDING: A COMBINATION OF "BOTTOM-UP" AND "TOP-DOWN"

A novel nanofabrication method that combines both "bottom-up" (template-assisted peptide self-assembling) and "top-down" (replica molding) techniques is introduced. A designer peptide, GAV-9 (NH2-VGGAVVAGV-CONH2), can epitaxially self-assemble into nanofilaments on the surface of mica, which is further used as the diversified masters for the application of replica molding. With in situ atomic force microscopy monitoring, several typical masters are fabricated by peptide self-assembling on the surface of mica. These masters can be easily molded into hard poly(dimethylsiloxane) surfaces, and then further replica-molded into polyurethane surfaces. The polymeric surfaces with regular 1D and 2D patterns on the nanometer scale are expected to have new applications in nanostructure's fabrication.Peptide, self-assembly, nanofabrication, replica molding, atomic force microscopy

Depth-Dependent Controls Over Soil Organic Carbon Stock across Chinese Shrublands

Soil organic carbon (SOC) in shrublands is an important component of global carbon cycling. However, there is a dearth of large-scale systematic observations of SOC stocks at different soil depths, and it remains uncertain whether and how the relative importance of biotic and abiotic variables in regulating SOC stocks changes with soil depth. Here, we quantified large-scale patterns and controlling factors of SOC storage per area (SOCD, kg m(-2)) for both topsoils (0-30 cm) and subsoils (30-100 cm) by taking full advantage of a consistent stratified random sampling study of one-meter soil profiles across 1211 sites in Chinese shrublands. We found that subsoils stored about 53.30% of total SOCD, falling into the range of previously reported values for terrestrial ecosystems. SoilGrids250m model-derived assessments overestimated SOCD by 13.72 and 65.49% for topsoils and subsoils, respectively. The effects of climate means and seasonality on SOCD were equally strong in both topsoils and subsoils. The predominant effects of edaphic properties on SOCD were more robust in subsoils than in topsoils. Belowground biomass of shrublands was the only significant predictor of topsoil SOCD, but it did not predict subsoil SOCD accurately. These findings have refined our understanding of the pivotal role of shrublands in SOC storage and sequestration potential and could serve as an ecologically valuable baseline for large-scale improvement and validation of depth-dependent SOC dynamics for multilayer SOC modules in Earth Systems Models

Metal-Free Radical [3 + 2] Annulation of Tetraalkylthiuram Disulfide with Alkynes/Alkenes: An Approach of Synthesizing 1,3-Dithiole and 1,3-Ditholane Derivatives

A novel and metal-free [3 + 2] annulation of tetraalkylthiuram disulfide with alkynes/alkenes has been developed using Selectfluor at room temperature. The formed 1,3-dithiol-2-ylium/1,3-dithiolan-2-ylium salts can be easily transformed into the corresponding 1,3-dithiol-2-ylidenes/1,3-ditholan-2-ylidenes by one-pot subsequent condensation with malononitrile. The present protocol features the use of easily accessible starting materials, mild reaction conditions, good tolerance with diverse functional groups, easy scale-up, and a wide substrate scope, affording the desired products in good yields. Importantly, this method is suitable for the late-stage modification of bioactive molecules. Furthermore, 1,3-dithiol-2-ylium salt can also be easily converted into various 1,3-dithiole derivatives by condensation, reduction, or hydrolysis. Mechanism studies show that this transformation involves radical annulation. Of note, this method presented a novel example using tetraalkylthiuram disulfide as a sulfur synthon in annulation, which greatly enriches the application of tetraalkylthiuram disulfides in organic synthesis. Biological evaluation indicates that these prepared compounds are promising candidates in terms of their antitumor activity

Psychosocial interventions for Alzheimer’s disease cognitive symptoms: a Bayesian network meta-analysis

Abstract Background Alzheimer disease (AD) is the most common type of dementia with cognitive decline as one of the core symptoms in older adults. Numerous studies have suggested the value of psychosocial interventions to improve cognition in this population, but which one should be preferred are still matters of controversy. Consequently, we aim to compare and rank different psychosocial interventions in the management of mild to moderate AD with cognitive symptoms. Methods We did a network meta-analysis to identify both direct and indirect evidence in relevant studies. We searched MEDLINE, EMBASE, PsycINFO through the OVID database, CENTRAL through the Cochrane Library for clinical randomized controlled trials investigating psychosocial interventions of cognitive symptoms in patients with Alzheimer disease, published up to August 31, 2017. We included trials of home-based exercise(HE), group exercise(GE), walking program(WP), reminiscence therapy(RT), art therapy(AT) or the combination of psychosocial interventions and acetylcholinesterase inhibitor (ChEIs). We extracted the relevant information from these trials with a predefined data extraction sheet and assessed the risk of bias with the Cochrane risk of bias tool. The outcomes investigated were Mini–Mental State Examination (MMSE) and compliance. We did a pair-wise meta-analysis using the fixed-effects model and then did a random-effects network meta-analysis within a Bayesian framework. Results We deemed 10 trials eligible, including 682 patients and 11 treatments. The quality of included study was rated as low in most comparison with Cochrane tools. Treatment effects from the network meta-analysis showed WP was better than control (SMD 4.89, 95% CI -0.07 to 10.00) while cognitive training and acetylcholinesterase inhibitor (CT + ChEIs) was significantly better than the other treatments, when compared with simple ChEIs treatment, assessed by MMSE. In terms of compliance, the pair-wise meta-analysis indicated that WP and HE are better than GE and AT, while CT + ChEIs, CST + ChEIs are better than other combined interventions. Conclusion Our study confirmed the effectiveness of psychosocial interventions for improving cognition or slowing down the progression of cognitive impairment in AD patients and recommended several interventions for clinical practice