Search

Fix a prime number p and let E / F be a CM extension of number fields in which p splits relatively. Let π be an automorphic representation of a quasi-split unitary group of even rank with respect to E / F such that π is ordinary above p with respect to the Siegel parabolic subgroup. We construct the cyclotomic p -adic L -function of π , and a certain generating series of Selmer classes of special cycles on Shimura varieties. We show, under some conditions, that if the vanishing order of the p -adic L -function is 1, then our generating series is modular and yields explicit nonzero classes (called Selmer theta lifts) in the Selmer group of the Galois representation of E associated with π ; in particular, the rank of this Selmer group is at least 1. In fact, we prove a precise formula relating the p -adic heights of Selmer theta lifts to the derivative of the p -adic L -function. In parallel to Perrin-Riou's p -adic analogue of the Gross–Zagier formula, our formula is the p -adic analogue of the arithmetic inner product formula recently established by Chao Li and the second author. [ABSTRACT FROM AUTHOR]

MQTT, a popular IoT messaging protocol, is frequently associated with numerous vulnerabilities, the majority of which are critical. Many IoT devices that utilize MQTT are susceptible to cyberattacks such as denial-of-service and buffer overflow. In this paper, we unveil a novel Denial of Service (DoS) attack in the MQTT protocol, referred to as Slow Subscribers, which has the potential to cause MQTT brokers to become single points of failure. Unlike existing MQTT DoS attacks, Slow Subscribers can occur on a single compromised node and could potentially disrupt a MQTT broker with minimal subscription permissions. We evaluated the reliability of Mosquitto and NanoMQ, two popular MQTT messaging brokers, to determine the effect of Slow Subscribers. According to the findings of our investigation, NanoMQ outperforms Mosquitto in response to the Slow Subscribers attack at QoS level 0. We also determine that the response to Slow Subscribers at QoS 2 is the worst for both broker implementations. In addition, the results of our experiments indicate that Eclipse Mosquitto achieves a higher rate of reliability than NanoMQ on cloud deployments whereas NanoMQ has proven to be well-suited for edge environments, especially edge IoT devices that require the use of QoS levels 0 and 1. Finally, we propose a Resilient Middleware for Message Queue Telemetry Transport (Remistry) framework that is capable of detecting misconfigurations while providing granular support of resource commitment errors, in particular the out-of-memory (OOM) problems for effectively mitigating the impact of Slow Subscribers attacks on MQTT brokers. [ABSTRACT FROM AUTHOR]

Intrahepatic cholestasis of pregnancy (ICP) is a rare liver disease occurring during pregnancy that is characterized by disordered bile acid (BA) metabolism. It is related to adverse clinical outcomes in both the mother and fetus. Our aim was to evaluate the BA metabolism profiles in different types of ICP and investigate the association between specific BAs and perinatal complications in ICP patients. We consecutively evaluated 95 patients with ICP, in which 53 patients were diagnosed with early-onset ICP (EICP) and 42 patients were diagnosed with late-onset ICP (LICP). Concentrations of 15 BA components were detected using high-performance liquid chromatography tandem mass spectrometry. Clinical information was abstracted from the medical records. The percentage of conjugated bile acids increased in ICP patients. Specifically, taurocholic acid (TCA) accumulated in LICP patients, and glycocholic acid (GCA) predominated in EICP patients. A higher preterm birth incidence was observed among ICP patients. Albumin, total bile acids, total bilirubin and GCA percentage values at ICP diagnosis predicts 83.5% of preterm birth in EICP, and the percentage of TCA in total bile acids at ICP diagnosis predicts 93.2% of preterm birth in LICP. This analysis showed that the BA metabolism profiles of EICP and LICP were distinct. Increased hepatic load was positively correlated with preterm birth in EICP. An elevated TCA percentage in total bile acids provides a biomarker to predict preterm birth in LICP. [ABSTRACT FROM AUTHOR]

We consider an irreversible dynamic pricing situation in which a firm uses real-time inventory information to decide the most opportune time to raise its sales prices. Feng and Xiao (Oper Res 48:332–343, 2000b) has studied this problem along with the opposite markdown case. In quite symmetric fashions, they established the optimality of threshold policies for both cases. Though the earlier work has made dramatic advances in dynamic pricing and at the same time pioneered with many relevant techniques, we believe its treatment of the markup case warrants some revision. In particular, we find it is in possession of an erstwhile-unknown complementarity property between price flexibility and inventory, whose counterpart is not true for the markdown case. This property is needed in the derivation leading to the optimality of a threshold policy. Our development also allows demand to be time-dependent in a product form, and naturally leads to an efficient policy-computing algorithm. [ABSTRACT FROM AUTHOR]

In this article, we study the Beilinson–Bloch–Kato conjecture for motives associated to Rankin–Selberg products of conjugate self-dual automorphic representations, within the framework of the Gan–Gross–Prasad conjecture. We show that if the central critical value of the Rankin–Selberg L-function does not vanish, then the Bloch–Kato Selmer group with coefficients in a favorable field of the corresponding motive vanishes. We also show that if the class in the Bloch–Kato Selmer group constructed from a certain diagonal cycle does not vanish, which is conjecturally equivalent to the nonvanishing of the central critical first derivative of the Rankin–Selberg L-function, then the Bloch–Kato Selmer group is of rank one. [ABSTRACT FROM AUTHOR]

Paleo-pressure reconstruction in sedimentary basins is one of the most important aspects of hydrocarbon accumulation research. In view of the advantages and disadvantages of the current methods for paleo-pressure research, a new method to reconstruct the paleo-pressure is presented in this paper. According to the geological background, quantitative analyses of the factors that might control overpressure were first conducted to clarify the contributions of each mechanism during different geological periods. Pressure evolution was reconstructed by fluid-compaction modelling with constraints imposed by the paleo-pressures obtained from fluid inclusions or differential stress methods. Determining the mechanisms responsible for overpressures during geological history is the basic prerequisite for paleo-pressure research. Thus, quantitative studies were conducted of the contributions of disequilibrium compaction, gas charging, oil cracking, temperature reduction, and tectonic uplift and subsidence to overpressures. Three case studies of paleo-pressure reconstruction were performed for the Sinian strata in the Sichuan Basin, Ordovician strata in the north uplift in the Tarim Basin and the Permian strata in the Sulige Gas Field in the Ordos Basin, where these three study sites are normally pressured, weakly over-pressured and abnormally low pressured at present, respectively. The new method developed in this paper is very important for the practical reconstruction of the paleo-pressure in marine strata and ancient strata in deep basins. [ABSTRACT FROM AUTHOR]

Let E be an elliptic curve over $${{\mathbb {Q}}}$$ and A another elliptic curve over a real quadratic number field. We construct a $${{\mathbb {Q}}}$$ -motive of rank 8, together with a distinguished class in the associated Bloch-Kato Selmer group, using Hirzebruch-Zagier cycles, that is, graphs of Hirzebruch-Zagier morphisms. We show that, under certain assumptions on E and A, the non-vanishing of the central critical value of the (twisted) triple product L-function attached to ( E, A) implies that the dimension of the associated Bloch-Kato Selmer group of the motive is 0; and the non-vanishing of the distinguished class implies that the dimension of the associated Bloch-Kato Selmer group of the motive is 1. This can be viewed as the triple product version of Kolyvagin's work on bounding Selmer groups of a single elliptic curve using Heegner points. [ABSTRACT FROM AUTHOR]

Objectives: To explore the feasibility of pretreatment nonenhanced magnetic resonance imaging (MRI) in predicting insufficient biochemical response to ursodeoxycholic acid (UDCA) in patients with primary biliary cholangitis (PBC). Methods: From January 2009 to April 2022, consecutive PBC patients who were treated with UDCA and underwent nonenhanced MRI within 30 days before treatment were retrospectively enrolled. All MR images were independently evaluated by two blinded radiologists. Uni- and multivariable logistic regression analyses were performed to develop a predictive model for 12-month insufficient biochemical response. Model performances were evaluated by computing the area under the receiver operating characteristic curve (AUC), sensitivity, and specificity. Results: A total of 74 patients (50.6 ± 11.9 years; 62 females) were included. Three pretreatment MRI features, including hepatomegaly (odds ratio [OR]: 4.580; p = 0.011), periportal hyperintensity on T2-weighted imaging (T2WI) (OR: 4.795, p = 0.008), and narrowing of the bile ducts (OR: 3.491; p = 0.027) were associated with 12-month insufficient biochemical response in the multivariable analysis. A predictive model based on the above indicators had an AUC of 0.781, sensitivity of 85.4%, and specificity of 61.5% for predicting insufficient biochemical response. Conclusions: A noninvasive model based on three pretreatment MRI features could accurately predict 12-month insufficient biochemical response to UDCA in patients with PBC. Early identification of PBC patients at increased risk for insufficient response can facilitate the timely initiation of additional treatment. Clinical relevance statement: A noninvasive predictive model constructed by incorporating three pretreatment MRI features may help identify patients with primary biliary cholangitis at high risk of insufficient biochemical response to ursodeoxycholic acid and facilitate the timely initiation of additional treatment. Key Points: • Noninvasive imaging features based on nonenhanced pretreatment MRI may predict an insufficient biochemical response to UDCA in PBC patients. • A combined model based on three MRI features (hepatomegaly, periportal hyperintensity on T2-weighted imaging, and narrowing of the bile ducts) further improved the predictive efficacy for an insufficient biochemical response to UDCA in PBC patients, with high sensitivity and specificity. • The nomogram of the combined model showed good calibration and predictive efficacy for an insufficient biochemical response to UDCA in PBC patients. In particular, the calibration curve visualised the clinical applicability of the prediction model. [ABSTRACT FROM AUTHOR]

This study examined the effect of pouring temperature on the microstructure, tensile properties and hot-tearing susceptibility (HTS) of a high-pressure die-cast (HPDC) Al–Zn–Mg–Cu alloy. The microstructure and pore defects of the HPDC samples were analyzed, and a semi-quantitative assessment method was proposed to evaluate HTS for HPDC. Results showed that the pouring temperature has pronounced influence on the tensile properties and HTS of the HPDC Al–Zn–Mg–Cu alloy. The tensile strength and elongation reach the highest point at the near-liquidus pouring temperature of 650 °C and decrease with higher or lower pouring temperature, whereas the HTS value presents the opposite trend. Microstructural investigation showed that all tear surfaces had pores and Fe-rich compounds were present at grain boundaries in samples poured at semi-solid temperature. Higher porosity levels occurred with higher or lower pouring temperatures than 650 °C. With consideration of the combined action of porosity and Fe-rich compounds, the effect of pouring temperature on the tensile properties and HTS of the HPDC Al–Zn–Mg–Cu alloy could be well explained. [ABSTRACT FROM AUTHOR]

Autoimmune factors play an important role in premature ovarian insufficiency (POI). Human amniotic epithelial stem cells (hAESCs) have recently shown promising treatment effects on chemotherapy-induced POI. However, the therapeutic efficacy and underlying mechanisms of hAESCs in autoimmune POI remain to be investigated. In this study, we showed for the first time that intravenous transplantation of hAESCs could reside in the ovary of zona pellucida 3 peptide (pZP3) induced autoimmune POI mice model for at least 4 weeks. hAESCs could improve ovarian function and fertility, alleviate inflammation and reduce apoptosis of granulosa cells (GCs) in autoimmune POI mice. The transcriptome analysis of mice ovaries and in vitro co-cultivation experiments suggest that activation of the AKT and ERK pathways may be the key mechanism in the therapeutic effect of hAESCs. Our work provides the theoretical and experimental foundation for optimizing the administration of hAESCs, as well as the clinical application of hAESCs in autoimmune POI patients.Graphical Abstract: Autoimmune factors play an important role in premature ovarian insufficiency (POI). Human amniotic epithelial stem cells (hAESCs) have recently shown promising treatment effects on chemotherapy-induced POI. However, the therapeutic efficacy and underlying mechanisms of hAESCs in autoimmune POI remain to be investigated. In this study, we showed for the first time that intravenous transplantation of hAESCs could reside in the ovary of zona pellucida 3 peptide (pZP3) induced autoimmune POI mice model for at least 4 weeks. hAESCs could improve ovarian function and fertility, alleviate inflammation and reduce apoptosis of granulosa cells (GCs) in autoimmune POI mice. The transcriptome analysis of mice ovaries and in vitro co-cultivation experiments suggest that activation of the AKT and ERK pathways may be the key mechanism in the therapeutic effect of hAESCs. Our work provides the theoretical and experimental foundation for optimizing the administration of hAESCs, as well as the clinical application of hAESCs in autoimmune POI patients. [ABSTRACT FROM AUTHOR]

Under the multiple stresses of global warming and human activities, land degradation in the Three River Source Region is becoming increasingly severe. However, the researches on large-scale land degradation monitoring models based on remote sensing are fewer and not yet mature. In this study, based on MODIS data products, five factors, including surface albedo, greenness index, heat index, topsoil grain size index, and salinity index, are introduced. These five factors are used to propose a novel large-scale land degradation remote sensing index based on the dynamic weighting method in Three River Source Region. Then the spatio-temporal evolution and driving mechanism of land degradation in the past 20 years are analyzed. The results showed that: (1) The land degradation remote sensing index model proposed in this study has good applicability, and its monitoring accuracy is 92.1%. (2) The average intensity of land degradation in the past 20 years in the Three River Source Region is 0.34, which generally belonged to the mild and moderate degradation. The Yangtze River Source Region has the most significant intensity of land degradation. (3) The gravity center of land degradation in the Three River Source Region during 2001–2020 generally shows a trend of eastward migration. (4) From 2001 to 2020, the change of land degradation intensity in the Three River Source Region was small, showing a trend of overall stability and a slight partial improvement. (5) The impacts of temperature, precipitation, and GDP density on land degradation are significantly different. From 2001 to 2020, the soil was the dominant factor determining land degradation, while the correlation between temperature and land degradation intensity in the study area was small. The results can provide relevant theoretical and technical support for land degradation management and ecological environment restoration in the Three River Source Region. [ABSTRACT FROM AUTHOR]

Purpose: Whether navigated total knee arthroplasty can improve the limb and component alignment is a matter of debate. This systematic literature review analyzed the differences on alignment outcomes between navigated total knee arthroplasty and conventional total knee arthroplasty. Methods: Multiple databases, online registers of randomized controlled trials were searched. Published and unpublished randomized controlled trials were included, and data on methodological quality, population, intervention, and outcomes were abstracted in duplicate. Data were pooled across studies, and odds ratios for categorical outcomes were calculated according to study sample size. Results: Twenty-one randomized controlled trials of varying methodological quality involving 2,414 patients were included. Statistically significant differences were observed between navigated group and conventional group in mechanical axis malalignment of >3° (odds ratio, 0.26; 95% confidence interval, 0.17-0.38) and mechanical axis malalignment of >2° (odds ratio, 0.33; 95% confidence interval, 0.26-0.42). Navigated group had a lower risk of malalignment for both coronal femoral component and coronal tibial component of >3° and >2°. Both sagittal femoral component alignment and tibial slope showed statistical significance in favor of navigated arthroplasty at >2° and 3° malalignment. Conclusion: Meta-analysis indicates significant improvement in alignment of the limb and the component position with use of computer navigation system. Its clinical benefits are unclear and remain to be defined on a larger scale randomized controlled trials with long-term follow-up. Level of evidence: Therapeutic study (Systematic review of Level-I studies with inconsistent results), Level II. [ABSTRACT FROM AUTHOR]

Purpose: The occurrence of diminished ovarian reserve (DOR) in women was growing in recent years. Although in vitro fertilization and embryo transfer (IVF-ET) became an effective treatment for DOR, the live-birth (LB) rate remains unsatisfactory. This study aimed to investigate the impact factors of LB rate in women with DOR undergoing assisted reproduction.Methods: This was a single-center retrospective cohort study. A total of 2277 IVF-ET or ICSI cycles from 1957 DOR women were analysed. Impact factors of LB rate were explored via Student's t test, Pearson's Chi-square test, and multivariate logistic regression models.Results: There were statistically significant differences in maternal age (P < 0.001), duration of infertility (P < 0.001), female body mass index (P = 0.039), first IVF cycle (P = 0.004), poor ovarian response (P < 0.001), paternal age (P < 0.001), total gonadotropin dose (P = 0.010), endometrial thickness (P = 0.021), number of follicles ≥ 14 mm (P = 0.007), number of oocytes retrieved (P < 0.001), number of frozen embryos (P = 0.014), and the stage (P < 0.001) and number (P < 0.001) of embryos transferred between the non-live-birth (NLB) and LB groups. However, only factors of maternal age, the stage and number of embryos transferred remained different after adjusting for potential confounders.Conclusions: Maternal age, the stage and number of embryos transferred were independent impact factors affecting the live-birth rate in women with DOR seeking for assisted conception. [ABSTRACT FROM AUTHOR]

Background: Previously, it has been shown that obesity may be considered as a risk factor for breast cancer in postmenopausal women. Leptin, a hormone whose level is elevated in obesity, has been suggested to be involved in the development of breast cancer, and univariate survival analyses have shown that over-expression of ACAT2, an enzyme that is involved in the production of cholesteryl esters, may be associated with a poor prognosis. Here, we aimed to investigate the effect of leptin on the proliferation, migration and invasion of breast cancer cells, as well as to elucidate its underlying mode of action. Methods: Gene expression changes in leptin treated breast cancer-derived MCF-7, T47D and BT474 cells were assessed using PCR array, qRT-PCR and Western blot analyses. The expression patterns of Ob-R (leptin receptor) and ACAT2 in breast cancer cells and primary breast cancer tissue samples were analyzed using immunofluorescence and immunohistochemistry, respectively. Leptin-induced proliferation of breast cancer cells was assessed using a CCK8 assay, and scratch wound and Transwell assays were used to assess breast cancer cell invasion and migration. Results: We found that, among the genes tested, ACAT2 expression exhibited the most significant changes in the leptin treated cells. In addition, we found that inhibition of ACAT2 expression using pyripyropene A (PPPA) or siRNA-mediated gene silencing significantly decreased leptin-induced proliferation, migration and invasion of MCF-7 and T47D cells. Subsequent Western blot analyses strongly indicated that the PI3K/AKT/SREBP2 signaling pathway was involved in leptin-induced ACAT2 upregulation in both MCF-7 and T47D cells. Finally, through the analysis of primary breast cancer tissue samples we found that ACAT2 may affect cancer progression through activation of the Ob-R. Conclusions: Our data indicate that leptin may enhance the proliferation, migration and invasion of breast cancer cells via ACAT2 up-regulation through the PI3K/AKT/SREBP2 signaling pathway. Therefore, the leptin/ACAT2 axis may represent an attractive therapeutic target for breast cancer, particularly in postmenopausal and/or obese women. [ABSTRACT FROM AUTHOR]