Shear strength of cemented sand gravel and rock materials

Shear strength is currently a significant parameter in the design of cemented sand gravel and rock (CSGR) dams. Shear strength tests were carried out to compare material without layers noumenon and layer condition. The experimental results showed good linearity in the curves of shear strength and pure grinding tests with correlation coefficients of nearly 97%. The friction coefficient was similar to that of C10 roller-compacted concrete (RCC), but the cohesion value was weaker than that of RCC. The shear strength of the CSGR layers decreased by 40% when retarding mixtures were not added and the layer was paved immediately after 4 h of waiting interval

A Facile Method to Enhance Photovoltaic Performance of Benzodithiophene-Isoindigo Polymers by Inserting Bithiophene Spacer

This study describes the synthesis and characterization of four polymers based on benzo[1,2-b:4,5-b']dithiophene (BDT) and isoindigo with zero, one, two, and three thiophene spacer groups. Results have demonstrated that the use of bithiophene as a spacer unit improves the geometry of the polymer chain, making it planar, and hence, potentially enhanced π- π stacking occurs. Due to favorable interaction of the polymer chains, enhanced absorption coefficient, and optimal morphology, PBDT-BTI, which possesses bithiophene as a spacer, revealed high current and fill factor leading to a power conversion efficiency of 7.3% in devices, making this polymer the best performing isoindigo-based material in polymer solar cells (PSCs). Also, PBDT-BTI could still maintain efficiency of over 6% with the active layer thickness of 270 nm, making it a potential candidate for a material in printed PSCs. These results demonstrate that the use of thiophene spacers in D-A polymers could be an important design strategy to produce high-performance PSCs

Discovery of a Selective, Substrate-Competitive Inhibitor of the Lysine Methyltransferase SETD8

The lysine methyltransferase SETD8 is the only known methyltransferase that catalyzes monomethylation of histone H4 lysine 20 (H4K20). Monomethylation of H4K20 has been implicated in regulating diverse biological processes including the DNA damage response. In addition to H4K20, SETD8 monomethylates non-histone substrates including proliferating cell nuclear antigen (PCNA) and promotes carcinogenesis by deregulating PCNA expression. However, selective inhibitors of SETD8 are scarce. The only known selective inhibitor of SETD8 to date is nahuoic acid A, a marine natural product, which is competitive with the cofactor. Here, we report the discovery of the first substrate-competitive inhibitor of SETD8, UNC0379 (1). This small-molecule inhibitor is active in multiple biochemical assays. Its affinity to SETD8 was confirmed by ITC (isothermal titration calorimetry) and SPR (surface plasmon resonance) studies. Importantly, compound 1 is selective for SETD8 over 15 other methyltransferases. We also describe structure–activity relationships (SAR) of this series

Strong aftershocks traffic light system: A case study of the 8 January 2022 MS6.9 Menyuan earthquake, Qinghai Province, China

Strong aftershocks, especially the disaster-causing M≥5.0 kind, are a key concern for mitigation of seismic risks because they often lead to superimposed earthquake damage. However, the real-time forecasting results of the traditional probability prediction models based on statistics are usually far from accurate and therefore unsatisfactory. Borrowing an idea from the foreshock traffic light system (FTLS), which is based on observations of decreasing b-values or increasing differential stress just before a strong aftershock, we constructed a strong aftershock traffic light system (SATLS) that uses data-driven technology to improve the reliability of time sequence b-value calculations, and analyzed the b-value variations of strong aftershocks in the China continent. We applied this system to the MS6.9 Menyuan earthquake occurred on 8 January 2022. The earthquake occurrence rates before the largest aftershock (MS5.2) forecast by the Omi-R-J model were too low, although the model could accurately forecast aftershock rates for each magnitude interval in most time-periods. However, reliable b-values can be calculated using the time-sequence b-value data-driven (TbDD) method, and the results showed that the b-values continued declining from 1.3 days before the MS5.2 aftershock and gradually recovered afterward. This would suggest that the stress evolution in the focal area can provide data for deciding when to post risk alerts of strong aftershocks. In the process of building the SATLS, we studied thirty-four M≥6.0 intraplate earthquake sequences in the China continent and concluded that the differences between the b-values of the aftershock sequences and of the background events, △b = bafter - bbg = ±0.1, could be used as thresholds to determine whether M≥5.0 aftershocks would occur. The △b value obtained using the events before the MS5.2 aftershock of the MS6.9 Menyuan sequence was about -0.04, which would have caused the SATLS to declare a yellow alert, but there would have been some gap expected before a red alert was triggered by the b-value difference derived from the events associated with this strong aftershock. To accurately forecast a strong aftershock of M≥5.0, a deeper understanding of the true b-value and a detailed description of the stress evolution state in the source area is necessary

Immune Protection of SIV Challenge by PD-1 Blockade During Vaccination in Rhesus Monkeys

Though immune correlates for protection are still under investigation, potent cytotoxic T lymphocyte responses are desirable for an ideal HIV-1 vaccine. PD-1 blockade enhances SIV-specific CD8+ T cells. However, little information has been reported about how it affects the immunogenicity and protection of prophylactic SIV vaccines in nonhuman primates. Here, we show that PD-1 blockade during vaccination substantially improved protective efficacy in SIV challenged macaques. The PD-1 pathway was blocked using a monoclonal antibody specific to human PD-1. Administration of this antibody effectively augmented and sustained vaccine-induced SIV-specific T cell responses for more than 42 weeks after first immunization in rhesus monkeys, as compared with SIV vaccination only. Importantly, after intrarectally repeated low-dosage challenge with highly pathogenic SIVmac239, monkeys with PD-1 blockade during vaccination achieved full protection against incremental viral doses of up to 50,000 TICD50. These findings highlight the importance of PD-1 blockade during vaccination for the development of HIV vaccines

Inflammatory-mediated repression of the rat ileal sodium-dependent bile acid transporter by c-fos nuclear translocation

AbstractBackground & Aims: Ileal malabsorption of bile salts is observed in Crohn's ileitis. We define the transcriptional mechanisms involved in cytokine-mediated repression of the rat apical sodium-dependent bile acid transporter (ASBT). Methods: ASBT regulation was studied in IL-1β–treated IEC-6 and Caco-2 cells and in indomethacin-treated rats. Results: Indomethacin-induced ileitis in Lewis rats leads to specific reductions in ileal ASBT messenger RNA and protein levels, whereas c-jun and c-fos are induced. The proinflammatory cytokines interleukin-1β and tumor necrosis factor repress the activity of the ASBT promoter in Caco-2 and intestinal epithelial cell-6 cells. This effect is blocked by the proteasome inhibitor, MG-132, or by the phosphatidyl inositol 3-kinase inhibitor, wortmannin. Indomethacin (in vivo) or proinflammatory cytokine (in vitro) treatment leads to serine phosphorylation and nuclear translocation of c-fos. Mutation of a 5' activated protein (AP)-1 site inactivates the ASBT promoter, whereas mutation of the 3' site abrogates the proinflammatory cytokine–mediated repression. The 5' site binds a c-jun homodimer, whereas the 3' site binds a c-jun/c-fos heterodimer. c-Jun overexpression enhances ASBT promoter activity, whereas a dominant negative c-jun construct inactivates the promoter. c-Fos overexpression represses promoter activity. A 27 base pair cis-element from the 3' site in the ASBT promoter imparts cytokine-mediated down-regulation to a heterologous SV40 promoter construct. Conclusions: The ASBT promoter contains 2 distinct cis AP-1 elements; the 5' element binds homodimeric c-jun and mediates basal transcription. Inflammation is associated with up-regulation, phosphorylation, and nuclear translocation of c-fos, which then represses ASBT promoter activity via binding of the 3' AP-1 element by a c-fos/c-jun heterodimer.GASTROENTEROLOGY 2002;123:2005-201

Diagnostic application of exome sequencing in Chinese children with suspected inherited kidney diseases

Background: Inherited kidney diseases (IKDs) are a group of kidney diseases characterized by abnormal kidney structure or function caused by genetic factors, but they are not easily diagnosed in childhood due to either nonspecific symptoms and signs or clinically silent symptoms in the early stages until the progressive stages, even end-stages. Early diagnosis of IKDs is very urgent for timely treatment and improving outcomes of patients. So far, the etiological diagnosis has been accelerated with the advance of clinical genetic technology, particularly the advent of next-generation sequencing (NGS) that is not only a powerful tool for prompt and accurate diagnosis of IKDs but also gives therapy guidance to decrease the risk of unnecessary and harmful interventions.Methods: The patients presenting with urinalysis abnormalities or structural abnormalities from 149 Chinese families were enrolled in this study. The clinical features of the patients were collected, and the potentially causative gene variants were detected using exome sequencing. The clinical diagnostic utility of the genetic testing was assessed after more detailed clinical data were analyzed.Result: In total, 55 patients identified having causative variants by exome sequencing were genetically diagnosed, encompassing 16 (29.1%) autosomal dominant IKDs, 16 (29.1%) autosomal recessive IKDs, and 23 (41.8%) X-linked IKDs, with 25 unreported and 45 reported variants. The diagnostic yield was 36.9%. The utility of the exome sequencing was accessed, 12 patients (21.8%) were confirmed to have suspected IKDs, 26 patients (47.3%) discerned the specific sub-types of clinical category, and 17 patients (30.9%) with unknown etiology or lack of typical manifestations were reclassified.Conclusion: Our study supported that genetic testing plays a crucial role in the early diagnosis for children with IKDs, which affected follow-up treatment and prognostic assessment in clinical practice. Moreover, the variant spectrum associated with IKDs was expanded

Apologies Repair Trust via Perceived Trustworthiness and Negative Emotions

The present study examined whether perceptions of a transgressor’s trustworthiness mediates the relationship between apologies and repaired trust, and the moderating role of negative emotions within this process. Chinese undergraduate students (N = 221) completed a trust game where they invested tokens in their counterpart, and either experienced no trust violation (i.e., half of the tokens returned), a trust violation (i.e., no tokens returned), or a trust violation followed by an apology. Participant’s trust behavior was measured by the number of tokens they re-invested in their counterpart in a second round of the game. Participants also completed measures to assess perceptions of the transgressor’s trustworthiness and emotional state. Results revealed that participants who received an apology were more likely to trust in their counterpart, compared to those who did not receive an apology, and this relationship was mediated by perceptions of the transgressor’s trustworthiness. Further, the relationship between apologies and perceptions of the transgressors trustworthiness was moderated by negative emotions; apologies only improved perceptions of trustworthiness for participants who experienced less negative emotions

Line identification of extreme ultraviolet spectra from aluminum ions in EAST Tokamak plasmas

Extreme ultraviolet (EUV) spectra emitted from aluminum in the 5-340 A wavelength range were observed in Experimental Advanced Superconducting Tokamak (EAST) discharges. Several spectral lines from aluminum ions with different degrees of ionization were successfully observed with sufficient spectral intensities and resolutions using three fast-time-response EUV spectrometers. The line identification uses three independent state-of-art computational codes for the atomic structure calculations, which provide the wavelengths and radiative transition probabilities rate coefficients. These programs are HULLAC (Hebrew University - Lawrence Livermore Atomic Code), AUTOSTRUCTURE, and FAC (Flexible Atomic Code). Using three different codes allows us to resolve some ambiguities in identifying certain spectral lines and assess the validity of the theoretical predictions