Secure and Effective Data Appraisal for Machine Learning

Essential for an unfettered data market is the ability to discreetly select and evaluate training data before finalizing a transaction between the data owner and model owner. To safeguard the privacy of both data and model, this process involves scrutinizing the target model through Multi-Party Computation (MPC). While prior research has posited that the MPC-based evaluation of Transformer models is excessively resource-intensive, this paper introduces an innovative approach that renders data selection practical. The contributions of this study encompass three pivotal elements: (1) a groundbreaking pipeline for confidential data selection using MPC, (2) replicating intricate high-dimensional operations with simplified low-dimensional MLPs trained on a limited subset of pertinent data, and (3) implementing MPC in a concurrent, multi-phase manner. The proposed method is assessed across an array of Transformer models and NLP/CV benchmarks. In comparison to the direct MPC-based evaluation of the target model, our approach substantially reduces the time required, from thousands of hours to mere tens of hours, with only a nominal 0.20% dip in accuracy when training with the selected data

Numerical Simulation of a Deep Excavation near a Shield Tunnel

A conveyance water shield tunnel under the Yangtze River, which was designed for the Jiangsu Changshu Power Plant Co., Ltd., was damaged due to water leakage and submersion. In order to complete the engineering, the shield tunnel should be repaired, and the connection between the shield and standpipes should be completed. Therefore, a deep excavation recovery program was designed. According to the excavation design, the distance between the axes of the two tunnels is only 20.8 m, but the depth of excavation reaches 15.1 m. Because of the small distance between the deep excavation and the adjacent west line tunnel, the new excavation in the east line tunnel might have large effects on the west line tunnel, and the environmental effects on the west tunnel due to the excavation should be evaluated. Simulations using 3D and 2D finite element methods were performed. The variations in the loads and lateral deformations on the retaining structures due to earth pressure differences outside and inside the foundation pit were analyzed in detail. The environmental effects on the west line tunnel due to deep excavation were evaluated. The 2D and 3D numerical simulation results were compared. The numerical simulation results agree with practical engineering and are applicable and reliable

Circulating vitamin levels mediate the causal relationship between gut microbiota and cholecystitis: a two-step bidirectional Mendelian randomization study

BackgroundThe relationship between gut microbiota and the occurrence of cholecystitis remains unclear. Existing research lacks a clear understanding of how circulating vitamin levels modulate this relationship. Therefore, our study aims to investigate whether circulating vitamin levels mediate the causal relationship between gut microbiota and cholecystitis using a two-step bidirectional Mendelian randomization approach.MethodsIn this study, we initially employed Linkage Disequilibrium Score Regression (LDSC) analysis to assess the genetic correlation of five circulating vitamin level genome-wide association study (GWAS) summary datasets, thereby avoiding potential sample overlap. Subsequently, we conducted a two-step analysis to investigate the causal effects between gut microbiota and cholecystitis. In the second step, we explored the causal relationship between circulating vitamin levels and cholecystitis and identified the mediating role of vitamin D. The primary method used for causal analysis was the inverse variance-weighted approach. We performed additional sensitivity analyses to ensure result robustness, including the cML-MA method and reverse Mendelian randomization (MR) analysis.ResultsAn increment of one standard deviation in RuminococcaceaeUCG003 was associated with a 25% increased risk of cholecystitis (OR = 1.25, 95%CI = 1.01–1.54, p = 0.04), along with a 3% decrease in 25-hydroxyvitamin D levels (OR = 0.97, 95%CI = 0.944–0.998, p = 0.04). However, following the rigorous Bonferroni correction, every one standard deviation decrease in circulating vitamin D levels was associated with a 33% increased risk of cholecystitis (OR = 0.67, 95%CI = 0.49–0.90, p = 0.008, Padjust = 0.04). Thus, the potential link between gut microbiota and cholecystitis risk might be mediated by circulating vitamin D levels (proportion mediated = 5.5%). Sensitivity analyses provided no evidence of pleiotropy.ConclusionOur study results suggest that an elevated abundance of specific gut microbiota is associated with an increased susceptibility to cholecystitis, with the causal relationship being mediated by circulating vitamin D levels. Further large-scale randomized controlled trials are necessary to validate the causal effects of gut microbiota on cholecystitis risk. This study provides novel insights into cholecystitis prevention through the regulation of gut microbiota

A proteomic view of Caenorhabditis elegans caused by short-term hypoxic stress

<p>Abstract</p> <p>Background</p> <p>The nematode <it>Caenorhabditis elegans </it>is both sensitive and tolerant to hypoxic stress, particularly when the evolutionarily conserved hypoxia response pathway HIF-1/EGL-9/VHL is involved. Hypoxia-induced changes in the expression of a number of genes have been analyzed using whole genome microarrays in <it>C. elegans</it>, but the changes at the protein level in response to hypoxic stress still remain unclear.</p> <p>Results</p> <p>Here, we utilized a quantitative proteomic approach to evaluate changes in the expression patterns of proteins during the early response to hypoxia in <it>C. elegans</it>. Two-dimensional difference gel electrophoresis (2D-DIGE) was used to compare the proteomic maps of wild type <it>C. elegans </it>strain N2 under a 4-h hypoxia treatment (0.2% oxygen) and under normoxia (control). A subsequent analysis by MALDI-TOF-TOF-MS revealed nineteen protein spots that were differentially expressed. Nine of the protein spots were significantly upregulated, and ten were downregulated upon hypoxic stress. Three of the upregulated proteins were involved in cytoskeletal function (LEV-11, MLC-1, ACT-4), while another three upregulated (ATP-2, ATP-5, VHA-8) were ATP synthases functionally related to energy metabolism. Four ribosomal proteins (RPL-7, RPL-8, RPL-21, RPS-8) were downregulated, indicating a decrease in the level of protein translation upon hypoxic stress. The overexpression of tropomyosin (LEV-11) was further validated by Western blot. In addition, the mutant strain of <it>lev-11(x12</it>) also showed a hypoxia-sensitive phenotype in subsequent analyses, confirming the proteomic findings.</p> <p>Conclusions</p> <p>Taken together, our data suggest that altered protein expression, structural protein remodeling, and the reduction of translation might play important roles in the early response to oxygen deprivation in <it>C. elegans</it>, and this information will help broaden our knowledge on the mechanism of hypoxia response.</p

Phases and magnetism at the microscale in compounds containing nominal Pb10-xCux(PO4)6O

Achieving superconductivity at room temperature could lead to substantial advancements in industry and technology. Recently, a compound known as Cu-doped lead-apatite, Pb10-xCux(PO4)6O (0.9 < x < 1.1), referred to as "LK-99", has been reported to exhibit unusual electrical and magnetic behaviors that appear to resemble a superconducting transition above room temperature. In this work we collected multiphase samples containing the nominal Pb10-xCux(PO4)6O phase (no superconductivity observed in our measured samples), synthesized by three independent groups, and studied their chemical, magnetic, and electrical properties at the microscale to overcome difficulties in bulk measurements. Through the utilization of optical, scanning electron, atomic force, and scanning diamond nitrogen-vacancy microscopy techniques, we are able to establish a link between local magnetic properties and specific microscale chemical phases. Our findings indicate that while the Pb10-xCux(PO4)6O phase seems to have a mixed magnetism contribution, a significant fraction of the diamagnetic response can be attributed to Cu-rich regions (e.g., Cu2S derived from a reagent used in the synthesis). Additionally, our electrical measurements reveal the phenomenon of current path switch and a change in resistance states of Cu2S. This provides a potential explanation for the electrical behavior observed in compounds related to Pb10-xCux(PO4)6O.Comment: 14 pages, 5 figures; Physical Review Material

SUMOylation of Grb2 enhances the ERK activity by increasing its binding with Sos1

BACKGROUND: Grb2 (Growth factor receptor-bound protein 2) is a key adaptor protein in maintaining the ERK activity via linking Sos1 (Son of sevenless homolog 1) or other proteins to activated RTKs, such as EGFR. Currently, little knowledge is available concerning the post-translational modification (PTM) of Grb2 except for its phosphorylation. Since emerging evidences have highlighted the importance of SUMOylation (Small ubiquitin-related modifier), a reversible PTM, in modulating protein functions, we wondered if Grb2 could be SUMOylated and thereby influences its functions especially involved in the Ras/MEK/ERK pathway. METHODS: SUMOylation of Grb2 was analyzed with the in vivo SUMOylation assay using the Ni(2+)-NTA affinity pulldown and the in vitro E.coli-based SUMOylation assay. To test the ERK activity and cell transformation, the murine fibroblast cell line NIH/3T3 and the murine colon cancer cell line CMT-93 were used for the experiments including Grb2 knockdown, ectopic re-expression, cell transformation and migration. Immunoprecipitation (IP) was employed for seeking proteins that interact with SUMO modified Grb2. Xenograft tumor model in mice was conducted to verify that Grb2 SUMOylation regulated tumorigenesis in vivo. RESULTS: Grb2 can be SUMOylated by SUMO1 at lysine 56 (K(56)), which is located in the linker region between the N-terminal SH3 domain and the SH2 domain. Knockdown of Grb2 reduced the ERK activity and suppressed cell motility and tumorigenesis in vitro and in vivo, which were all rescued by stable ectopic re-expression of wild-type Grb2 but not the mutant Grb2(K56R). Furthermore, Grb2 SUMOylation at K(56) increased the formation of Grb2-Sos1 complex, which sequentially leads to the activation of Ras/MEK/MAPK pathway. CONCLUSIONS: Our results provide evidences that Grb2 is SUMOylated in vivo and this modification enhances ERK activities via increasing the formation of Grb2-Sos1 complex, and may consequently promote cell motility, transformation and tumorigenesis

A Novel CRYGD Mutation (p.Trp43Arg) Causing Autosomal Dominant Congenital Cataract in a Chinese Family

To identify the genetic defect associated with autosomal dominant congenital nuclear cataract in a Chinese family, molecular genetic investigation via haplotype analysis and direct sequencing were performed Sequencing of the CRYGD gene revealed a c.127T>C transition, which resulted in a substitution of a highly conserved tryptophan with arginine at codon 43 (p.Trp43Arg). This mutation co-segregated with all affected individuals and was not observed in either unaffected family members or in 200 normal unrelated individuals. Biophysical studies indicated that the p.Trp43Arg mutation resulted in significant tertiary structural changes. The mutant protein was much less stable than the wild-type protein, and was more prone to aggregate when subjected to environmental stresses such as heat and UV irradiation. © 2010 Wiley-Liss, Inc