On the Robustness of Generative Retrieval Models: An Out-of-Distribution Perspective

Recently, we have witnessed generative retrieval increasingly gaining attention in the information retrieval (IR) field, which retrieves documents by directly generating their identifiers. So far, much effort has been devoted to developing effective generative retrieval models. There has been less attention paid to the robustness perspective. When a new retrieval paradigm enters into the real-world application, it is also critical to measure the out-of-distribution (OOD) generalization, i.e., how would generative retrieval models generalize to new distributions. To answer this question, firstly, we define OOD robustness from three perspectives in retrieval problems: 1) The query variations; 2) The unforeseen query types; and 3) The unforeseen tasks. Based on this taxonomy, we conduct empirical studies to analyze the OOD robustness of several representative generative retrieval models against dense retrieval models. The empirical results indicate that the OOD robustness of generative retrieval models requires enhancement. We hope studying the OOD robustness of generative retrieval models would be advantageous to the IR community.Comment: 4 pages, submit to GenIR2

Modulating β-catenin/BCL9 interaction with cell-membrane-camouflaged carnosic acid to inhibit Wnt pathway and enhance tumor immune response

IntroductionLung adenocarcinoma (LUAD) therapies are plagued by insufficient immune infiltration and suboptimal immune responses in patients, which are closely associated with the hyperactive Wnt/β-catenin pathway. Suppressing this signaling holds considerable promise as a potential tumor therapy for LUAD, but Wnt suppressor development is hindered by concerns regarding toxicity and adverse effects due to insufficient targeting of tumors.MethodsWe have synthesized a tumor-specific biomimetic Wnt pathway suppressor, namely CM-CA, by encapsulating carnosic acid within Lewis lung carcinoma (LLC) cell membranes. It possesses nano-size, allowing for a straightforward preparation process, and exhibits the ability to selectively target the Wnt/β-catenin pathway in lung adenocarcinoma cells. To evaluate its in vivo efficacy, we utilized the LLC Lewis homograft model, and further validated its mechanism of action through immunohistochemistry staining and transcriptome sequencing analyses.ResultsThe findings from the animal experiments demonstrated that CM-CA effectively suppressed the Wnt/β-catenin signaling pathway and impeded cellular proliferation, leading to notable tumor growth inhibition in a biologically benign manner. Transcriptome sequencing analyses revealed that CM-CA promoted T cell infiltration and bolstered the immune response within tumor tissues.ConclusionThe utilization of CM-CA presents a novel and auspicious approach to achieve tumor suppression and augment the therapeutic response rate in LUAD, while also offering a strategy for the development of Wnt/β-catenin inhibitors with biosafety profile

Nondestructive determination of subsurface grain morphology

Recent progress in experimental and numerical methods enables to scrutinize simulated polycrystal surface micromechanics at high spatial resolution. For the correct interpretation of similarities and deviations between experiment and simulation, the consideration of subsurface grain morphology is imperative because of its significant impact on the surface layer boundary condition. A novel method is presented that coarsely scans a relatively large area for subsurface crystallite orientation up to depths of ~0.2 mm by means of differential aperture X-ray microscopy. The resulting point set is categorized into grains according to proximity in physical and orientation space. Reconstruction of the subsurface grain structure starts with a Voronoi tessellation using the categorized set as seed points. Progressive smoothing of the resulting ragged grain boundary surfaces is achieved through mean curvature flow. As it turns out that the reconstruction quality of the bulk and on the surface are related, the latter can serve as guidance for optimum subsurface reconstruction

Local elastic strain and strain tensor measurements of deformed metals using focused, submicrometer Xrays

The use of depth resolved, submicrometer X-ray beams for studying deformation microstructures in plastically deformed metals has come a long way over the past 5 years. We can identify phases, measure crystallographic orientations, and measure lattice constants from buried, submicrometer sample volumes throughout extended sample regions within single crystal and polycrystalline samples. In special cases, we can also measure both deviatoric and complete elastic strain tensors with reliable uncertainty estimates for the tensor components. Examples of these capabilities will be described, including nondestructive, full strain tensor measurements from through-Si vias in microelectronics, and strain measurements from commercial Al alloys deformed using equal-channel angular pressing. Expectations for the future will also be discussed

Pectin supplementation ameliorates intestinal epithelial barrier function damage by modulating intestinal microbiota in lipopolysaccharide-challenged piglets.

peer reviewedDuring weaning, infants and young animals are susceptible to severe enteric infections, thus inducing intestinal microbiota dysbiosis, intestinal inflammation, and impaired intestinal barrier function. Pectin (PEC), a prebiotic polysaccharide, enhances intestinal health with the potential for a therapeutic effect on intestinal diseases. One 21-d study was conducted to investigate the protective effect of pectin against intestinal injury induced by intraperitoneal injection of Escherichia coli lipopolysaccharide (LPS) in a piglet model. A total of 24 piglets (6.77±0.92 kg BW; Duroc × Landrace × Large White; barrows; 21 d of age) were randomly assigned into three groups: control group, LPS-challenged group, and PEC + LPS group. Piglets were administrated with LPS or saline on d14 and d21 of the experiment. All piglets were slaughtered and intestinal samples were collected after 3 h administration on d21. Pectin supplementation ameliorated the LPS-induced inflammation response and damage to the ileal morphology. Meanwhile, pectin also improved intestinal mucin barrier function, increased the mRNA expression of MUC2, and improved intestinal mucus glycosylation. LPS challenge reduced the diversity of intestinal microbiota and enriched the relative abundance of Helicobacter. Pectin restored alpha diversity and improved the structure of the gut microbiota by enriching anti-inflammatory bacteria and short-chain fatty acids (SCFAs)-producing bacteria, and increased the concentrations of acetate. In addition, Spearman rank correlation analysis also revealed the potential relationship between intestinal microbiota and intestinal morphology, intestinal inflammation, and intestinal glycosylation in piglets. Taken together, these results indicate that pectin enhances intestinal integrity and barrier function by altering intestinal microbiota composition and their metabolites, which subsequently alleviates intestinal injury and finally improves the growth performance of piglets

Variation in superconducting transition temperature due to tetragonal domains in two-dimensionally doped SrTiO₃

Strontium titanate is a low-temperature, non-Bardeen-Cooper-Schrieffer superconductor that superconducts to carrier concentrations lower than in any other system and exhibits avoided ferroelectricity at low temperatures. Neither the mechanism of superconductivity in strontium titanate nor the importance of the structure and dielectric properties for the superconductivity are well understood. We studied the effects of twin structure on superconductivity in a 5.5-nm-thick layer of niobium-doped SrTiO$_{3}$ embedded in undoped SrTiO$_{3}$. We used a scanning superconducting quantum interference device susceptometer to image the local diamagnetic response of the sample as a function of temperature. We observed regions that exhibited a superconducting transition temperature $T_{c}$ $\gtrsim$ 10% higher than the temperature at which the sample was fully superconducting. The pattern of these regions varied spatially in a manner characteristic of structural twin domains. Our results emphasize that the anisotropic dielectric properties of SrTiO$_{3}$ are important for its superconductivity, and need to be considered in any theory of the mechanism of the superconductivity.Comment: 14 pages, 11 figures, Supplemental Information available at http://stanford.edu/group/moler/papers/Noad_STOsuperconductivity_SI.pd

Exposure to High Aerial Ammonia Causes Hindgut Dysbiotic Microbiota and Alterations of Microbiota-Derived Metabolites in Growing Pigs

Ammonia, an atmospheric pollutant in the air, jeopardizes immune function, and perturbs metabolism, especially lipid metabolism, in human and animals. The roles of intestinal microbiota and its metabolites in maintaining or regulating immune function and metabolism are irreplaceable. Therefore, this study aimed to investigate how aerial ammonia exposure influences hindgut microbiota and its metabolites in a pig model. Twelve growing pigs were treated with or without aerial ammonia (35 mg/m3) for 25 days, and then microbial diversity and microbiota-derived metabolites were measured. The results demonstrated a decreasing trend in leptin (p = 0.0898) and reduced high-density lipoprotein cholesterol (HDL-C, p = 0.0006) in serum after ammonia exposure. Besides, an upward trend in hyocholic acid (HCA), lithocholic acid (LCA), hyodeoxycholic acid (HDCA) (p < 0.1); a downward trend in tauro-deoxycholic acid (TDCA, p < 0.1); and a reduced tauro-HDCA (THDCA, p < 0.05) level were found in the serum bile acid (BA) profiles after ammonia exposure. Ammonia exposure notably raised microbial alpha-diversity with higher Sobs, Shannon, or ACE index in the cecum or colon and the Chao index in the cecum (p < 0.05) and clearly exhibited a distinct microbial cluster in hindgut indicated by principal coordinate analysis (p < 0.01), indicating that ammonia exposure induced alterations of microbial community structure and composition in the hindgut. Further analysis displayed that ammonia exposure increased the number of potentially harmful bacteria, such as Negativibacillus, Alloprevotella, or Lachnospira, and decreased the number of beneficial bacteria, such as Akkermansia or Clostridium_sensu_stricto_1, in the hindgut (FDR < 0.05). Analysis of microbiota-derived metabolites in the hindgut showed that ammonia exposure increased acetate and decreased isobutyrate or isovalerate in the cecum or colon, respectively (p < 0.05). Unlike the alteration of serum BA profiles, cecal BA data showed that high ammonia exposure had a downward trend in cholic acid (CA), HCA, and LCA (p < 0.1); a downward trend in deoxycholic acid (DCA) and HDCA (p < 0.05); and an upward trend in glycol-chenodeoxycholic acid (GCDCA, p < 0.05). Mantel test and correlation analysis revealed associations between microbiota-derived metabolites and ammonia exposure-responsive cecal bacteria. Collectively, the findings illustrated that high ammonia exposure induced the dysbiotic microbiota in the hindgut, thereby affecting the production of microbiota-derived short-chain fatty acids and BAs, which play a pivotal role in the modulation of host systematic metabolism

Effects of Xylo-Oligosaccharides on Growth and Gut Microbiota as Potential Replacements for Antibiotic in Weaning Piglets.

Xylo-oligosaccharides (XOS) is a well-known kind of oligosaccharide and extensively applied as a prebiotic. The objective of this study was to investigate the effect of XOS supplementation substituting chlortetracycline (CTC) on growth, gut morphology, gut microbiota, and hindgut short chain fatty acid (SCFA) contents of weaning piglets. A total of 180 weaned piglets were randomly allocated to three treatments for 28 days, as follows: control group (basal diet, CON), basal diet with 500 mg/kg (XOS500) XOS, and positive control (basal diet with 100 mg/kg CTC). Compared with the CON group, the piglets in the XOS500 group improved body weight (BW) on days 28, average daily gain (ADG) and reduced feed: gain ratio during days 1-28 (P < 0.05). The XOS500 supplementation increased Villus height and Villus height: Crypt depth ratio in the ileum (P < 0.05). Villus Height: Crypt Depth of the ileum was also increased in the CTC treatment group (P < 0.05). Meanwhile, the XOS500 supplementation increased significantly the numbers of goblet cells in the crypt of the cecum. High-throughput 16S rRNA gene sequencing revealed distinct differences in microbial compositions between the ileum and cecum. XOS500 supplementation significantly increased the bacterial diversity. However, CTC treatment markedly reduced the microbial diversity (P < 0.05). Meanwhile, XOS500 supplementation in the diet significantly increased the abundance of Lactobacillus genus compared to the CON and CTC group in the ileum and cecum (P < 0.01), whereas the level of Clostridium_sensu_stricto_1, Escherichia-Shigella, and Terrisporobacter genus in the XOS500 group were markedly lower than the CON and CTC group (P < 0.05). In addition, dietary supplementation with XOS500 significantly increased the total short-chain fatty acids, propionate and butyrate concentrations and decreased the acetate concentration compared to the CON group in the cecum (P < 0.05). In summary, dietary supplemented with XOS500 could enhance specific beneficial microbiota abundance and decrease harmful microbiota abundance to maintain the structure of the intestinal morphology and improve growth performance of weaned piglets. Thus, XOS may potentially function as an alternative to in-feed antibiotics in weaned piglets in modern husbandry

Taxifolin increased semen quality of Duroc boars by improving gut microbes and blood metabolites.

peer reviewedTaxifolin (TAX), as a natural flavonoid, has been widely focused on due to its strong anti-oxidation, anti-inflammation, anti-virus, and even anti-tumor activity. However, the effect of TAX on semen quality was unknown. The purpose of this study was to analyze the beneficial influences of adding feed additive TAX to boar semen in terms of its quality and potential mechanisms. We discovered that TAX increased sperm motility significantly in Duroc boars by the elevation of the protein levels such as ZAG, PKA, CatSper, and p-ERK for sperm quality. TAX increased the blood concentration of testosterone derivatives, antioxidants such as melatonin and betaine, unsaturated fatty acids such as DHA, and beneficial amino acids such as proline. Conversely, TAX decreased 10 different kinds of bile acids in the plasma. Moreover, TAX increased "beneficial" microbes such as Intestinimonas, Coprococcus, Butyrivibrio, and Clostridium_XlVa at the Genus level. However, TAX reduced the "harmful" intestinal bacteria such as Prevotella, Howardella, Mogibacterium, and Enterococcus. There was a very close correlation between fecal microbes, plasma metabolites, and semen parameters by the spearman correlation analysis. Therefore, the data suggest that TAX increases the semen quality of Duroc boars by benefiting the gut microbes and blood metabolites. It is supposed that TAX could be used as a kind of feed additive to increase the semen quality of boars to enhance production performance