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We consider the problem of testing the equality of conditional distributions of a response variable given a vector of covariates between two populations. Such a hypothesis testing problem can be motivated from various machine learning and statistical inference scenarios, including transfer learning and causal predictive inference. We develop a nonparametric test procedure inspired from the conformal prediction framework. The construction of our test statistic combines recent developments in conformal prediction with a novel choice of conformity score, resulting in a weighted rank-sum test statistic that is valid and powerful under general settings. To our knowledge, this is the first successful attempt of using conformal prediction for testing statistical hypotheses beyond exchangeability. Our method is suitable for modern machine learning scenarios where the data has high dimensionality and large sample sizes, and can be effectively combined with existing classification algorithms to find good conformity score functions. The performance of the proposed method is demonstrated in various numerical examples., 46 pages, 2 figures, 7 tables; to appear in Journal of the American Statistical Association

Additional file 1: Figure S1. SARA induces mastitis in cows. Cows were treated with a standard or high-grain diet for two months and ruminal, serum, milk and mammary gland tissues were harvested for analysis. A. Ruminal PH at day 60 from Health and SARA cows (n=6). B-C. Ruminal and serum LPS levels were detected using ELISA (n=6). D. Somatic cell count was performed in Health and SARA cows (n=6). E. Representative images of H&E-stained sections from Health and SARA samples. Red arrows indicate leukocyte infiltration. Blue arrows show the structure injury of mammary gland. Black arrows indicate edema. F. Histological score based on H&E-stained sections (n=6). Mammary TNF-α (G) and IL-1β (H) from Health and SARA groups were measured by ELISA (n=6). Each dot represents an individual cow (A-D and F-H) and Student’s t test was performed (A-D and F-H). **p < 0.01, ***p < 0.001 indicate significance. Figure S2. Data quality checks. A. The Pearson correlation of ruminal QC samples. B-C. The PCA score plots for Health and SARA samples containing QC samples (n=6). QC, quality control; PCA, Principal component analysis. Figure S3. Classification and functional annotation of metabolites. A. KEGG pathway annotation for Health and SARA ruminal samples. B. HMDB classification annotation. C. Lipid maps annotation for Health and SARA groups. HMDB, Human Metabolome Database; KEGG, Kyoto Encyclopedia of Genes and Genomes. Figure S4. SARA induced ruminal metabolic changes. A. PLS-DA score plots for ruminal samples (n=6). B. Cross-validation plot with a permutation test repeated 200 times. The intercepts of R2 (0.0, 0.57) and Q2 (0.0,–1.09) indicate that the PLS-DA model was not overfitting. C. Pathway enrichment analysis of significantly elevated metabolites in SARA sample according to the KEGG pathway. Figure S5. Spearman correlation between metabolites and inflammatory parameters. The red color denotes a positive correlation, while green color denotes a negative correlation. The intensity of the color is proportional to the strength of Spearman correlation. *p < 0.05, **p < 0.01, ***p < 0.001 indicate significance. Figure S6. Spearman correlation among metabolites. The top 20 correlated metabolites were showed based on the P value. The red color denotes a positive correlation, while blue color denotes a negative correlation. Figure S7. SA and FMT change the intestinal SA levels. A-B. The intestinal SA levels from different treatment groups (n=6-8). Data are expressed as the mean ± SD (A-B) and one-way ANOVA was performed, followed by Tukey test (A-B). *p < 0.05, **p < 0.01, ***p < 0.001 indicate significant difference. Figure S8. Sialic acid treatment has minimum effects on the synthesis of milk proteins and ileum histology. A-D. Relative mammary gene expressions associated with the synthesis of milk proteins from indicated groups, including Csn1, Csn2, Csn3, and Wap (n=7-8). E. The average weight changes of litters from different treatment groups (n=6). F. Representative images of H&E-stained ileum sections from indicated mice. G. Histological score based on H&E-stained sections (n=7-8). Figure S9. Composition of the gut microbiota in different groups. A. Chao1 index in different groups (n=7-8). B. Ace index (n=7-8). C. Bacterial composition at the family level in the gut were displayed (n=7-8). Each dot represents an individual mouse (A and B) and one-way ANOVA was performed, followed by Tukey test (A and B). ***p < 0.001 indicate significance. ns, no significance. Figure S10. Top 50 metabolism pathways enriched in different groups using Tax4Fun. Figure S11. Sodium tungstate treatment reduces intestinal Enterobacteriaceae abundance. A. The gut microbial compositions at the family level from different treatment groups (n=4). B. A Wilcoxon rank-sum test was performed to identify the differential bacterial taxa in the AN and AN+T groups (FDR < 0.05) (n=4). Figure S12. The ruminal and intestinal microbial compositions in the donor and recipient mice, and the effect of RMT on systemic inflammation in mice. A-D. Alpha diversity indices, including observed species (A), Shannon (B), Chao1 (C) and Simpson index (D), from Health and SARA groups (n=6). E. The ruminal microbial compositions at the family level from the indicated groups (n=6). F. Venn diagram showed the observed OTUs in different RMT groups. G-I. Alpha diversity indices, including Shannon (G), Chao1 (H) and Simpson index (I), from different treatment groups (n=7). J. The gut microbial compositions at the family level from different RMT groups (n=7). K-L. Serum TNF-α (K) and IL-1β (L) levels by ELISA (n=7). Data are expressed as boxplot (A-D and G-I) or the mean ± SD (K-L). A Student’s t test (A-D) or one-way ANOVA was performed, followed by Tukey test (G-I and K-L). *p < 0.05, **p < 0.01, ***p < 0.001 indicate significant difference. Figure S13. A high-starch diet promotes SA production and mastitis in SRMT mice. A. Neu5Ac levels from different treatment groups (n=5). B. Representative images of H&E-stained mammary sections. C. Histological scores based on H&E-stained mammary sections (n=5). D-F. Mammary TNF-α (D), IL-1β (E), MPO activity (F) were assessed (n=5). Data are expressed as the mean ± SD (C-F) and one-way ANOVA was performed, followed by Tukey test (C-F). **p < 0.01, ***p < 0.001 indicate significant difference. Table S1. Identified number of differential metabolites in Health and SARA samples. Table S2. Metabolites significantly upregulated in SARA cows and ranked according to the P-value. Table S3. Metabolites significantly downregulated in SARA cows and ranked according to the P-value. Table S4. The oligonucleotides used in this study.

OBJECTIVE: To systematically evaluate the effectiveness of Fuzheng Huayu preparation (扶正化瘀胶囊/片, FZHY) plus tenofovir disoproxil fumarate (TDF) on hepatitis B. METHODS: Numerous databases — PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure Database, WanFang Database, China Science and Technology Journal Database, and China Biological Medicine Database — were searched to identify the randomized controlled trials published from the inception of the database to November 2021. Two researchers independently conducted literature screening, data extraction, and bias risk assessment. RevMan 5.4 software was used for Meta-analysis. RESULTS: Eight studies involving 990 patients met the inclusion criteria in the current Meta-analysis. Levels of alanine transaminase, aspartate aminotransferase, total bilirubin, hyaluronic acid, type III procollagen, laminin, and type IV collagen after combination therapy were significantly lower than those after TDF therapy alone. However, albumin levels did not differ significantly between the two regimens. Subgroup analysis based on disease progression suggested that the combination therapy improved albumin levels in patients with chronic hepatitis B but not in patients with hepatitis B-related cirrhosis. Moreover, subgroup analysis based on treatment duration suggested that the albumin levels were increased and the type III procollagen levels were decreased with the > 24-week combination therapy but not with the ≤ 24-week combination therapy. CONCLUSIONS: A combination regimen of TDF and FZHY is more effective in treating hepatitis B than TDF alone. The combination therapy can effectively alleviate hepatic fibrosis and improve liver function. However, more standardized, high-quality studies with larger sample sizes are warranted to validate the study results.

Real Estate Investment Trust (REIT) is considered as a financial instrument operated and managed by professional management teams based on a range of income-producing real estate. The focus of this thesis is on publicly traded equity REITs. There are four research questions that this thesis attempts to answer. How did REITs develop in the United States (US)? What are the critical factors that incentivized the Chinese government to promote REITs, and what is the progress? Are REITs a good hedge against macroeconomic risk factors? How can the downside risk of REITs be evaluated? To begin, the first two questions have been answered using the literature review methodology. The VAR model is constructed to evaluate the relation between the REIT market and macroeconomic factors. Ultimately, downside risk of REIT market is assessed by the GARCH(1,1)-VaR model based on the student’s t-distribution. Keywords: Equity REITs; Macroeconomic risks; VAR; VaR; GARCH(1,1)., Junior Management Science, Bd. 7 Nr. 4 (2022)

Timely identification of pathogenic variants associated with liver cancer can help identify the risk of potential disease progression and determine health care options. However, the adoption of genetic testing services for liver cancer risk remains low in many countries. Interventions targeting individuals at potential risk for hereditary liver cancer to receive these services are often complex and have multiple components, making them difficult to implement, replicate, and disseminate to new settings. Our goal is to systematically review studies targeting genetic testing services for liver cancer risk and to critically assess the quality of implementation results and reporting of intervention descriptions.

In order to provide privacy provisioning for the secondary information, we propose an energy harvesting based secure transmission scheme for the cognitive multi-relay networks. In the proposed scheme, two secondary relays harvest energy to power the secondary transmitter and assist the secondary secure transmission without interfere the secondary transmission. Specifically, the proposed secure transmission policy is implemented into two phases. In the first phase, the secondary transmitter transmits the secrecy information and jamming signal through the power split method. After harvesting energy from a fraction of received radio-frequency signals, one secondary relay adopts the amplify-and-forward relay protocol to assist the secondary secure transmission and the other secondary relay just forwards the new designed jamming signal to protect the secondary privacy information and degrade the jamming interference at the secondary receiver. For the proposed scheme, we first analyze the average secrecy rate, the secondary secrecy outage probability, and the ergodic secrecy rate, and derive their closed-form expressions. Following the above results, we optimally allocate the transmission power such that the secrecy rate is maximized under the secrecy outage probability constraint. For the optimization problem, an AI based simulated annealing algorithm is proposed to allocate the transmit power. Numerical results are presented to validate the performance analytical results and show the performance superiority of the proposed scheme in terms of the average secrecy rate.

Objective To compare the effects of the combination of (Yishu) psychodrama versus general mental health education with antidepressants on clinical symptoms, coping style and neuroimaging features in patients with major depressive disorder (MDD) who experienced childhood trauma. Methods This prospective case-control study was conducted in MDD patients with childhood trauma recruited from our department of psychiatry. The patients were randomly assigned into observation group (n=16) for treatment with antidepressants combined with (Yishu) psychodrama and control group (n=16) treated with antidepressants and general mental health education, and selective serotonin reuptake inhibitors (SSRIs) was used as the main antidepressants for 6 months in both groups. After the interventions, the patients were assessed using Beck Depression Inventory-13 item (BDI-13), Beck Anxiety Inventory (BAI), and Trait Coping Style Questionnaire (TCSQ), and the amplitude of low frequency fluctuations (ALFF) in resting functional magnetic resonance imaging (fMRI) was determined and compared between the two groups. Results After 6 months of intervention, no significant differences were found in the changes of BDI score (P>0.05) or BAI score (P>0.05) between the two groups, but the changes in TCSQ positive score (P < 0.05) and TCSQ negative score (P < 0.01) differed significantly between them. Resting fMRI results showed 19 interactive brain regions (corrected by FDR, P < 0.05) in these patients. Post hoc analysis revealed that after the intervention, the patients in the observation group, as compared with the control patients, tended to have enhanced activation of the left medial superior frontal gyrus (P>0.05) and showed significant enhancement of activation in the right parahippocampal gyrus (P < 0.01) with attenuated activation in the left precuneus lobe (P < 0.05). Conclusion Antidepressants combined with psychodrama can more effectively modify the coping style of depressed patients with childhood trauma than the combination of medications and general mental health education, possibly due to the effect of psychodrama to enhance the activation of the right parahippocampal gyrus and attenuate the activation of the left anterior cuneiform lobe, which leads to reduction of the adverse effects of negative experiences on emotion and cognition-coping. Psychodrama combined with medications can be used in the treatment of depressed patients with childhood trauma.

Qijiaoshengbai capsule (QJSBC) is a type of proprietary Chinese medicine, which is an effective treatment for leukopenia in clinical practice. The purpose of this study is to evaluate the efficacy of QJSBC in improving specific clinical indicators, in patients with leukopenia of various origins. A total of seven electronic databases were searched, up until an end date of April 30, 2021, and a selection of clinical indicators was noted. The primary indicators of concern were related to blood: white blood cells (WBC). Secondary indicators were hemoglobin (Hb), platelets (PLT), neutrophils (NEU), bone marrow suppression rate (BMSR), and effective rate (ER). The methodological quality of the included trials was analyzed using a risk of bias assessment, as per the Cochrane Manual. The meta-analysis was performed using RevMan 5.4. Results. Twenty-four randomized controlled trials involving a total of 2,692 participants were included in this review. We found that QJSBC had a positive effect on increasing WBC, HB, PLT, and NEU and improving BMSR and ER. Conclusion. When compared with conventional chemotherapy (CC), conventional radiotherapy (CR), combined chemotherapy and radiotherapy (CC + CR), or conventional treatment (CT), the use of QJSBC combined therapy can effectively improve the clinical outcome for patients with leukopenia. However, a larger sample size and a more standardized, high-quality study are required to validate these results.

Background: Alcohol dependence is one of the biggest problems facing public health worldwide. Currently, it is an under-diagnosed and under-treated disease. Even when given treatments for addiction withdrawal, over 2/3 of patients who have undergone abstinence-oriented treatment will relapse in the first year. Therefore, it is necessary to find an efficacious way to prevent and treat alcohol dependence. ASF (a Compound of Traditional Chinese Medicine) has proven to inhibit the formation and expression of ethanol-induced behavioral sensitization and the development of conditioned place preference in mice. As an empirical prescription for abstinence from alcohol, ASF has long been used in clinical patients. However, the effect of ASF in humans has not yet been investigated. The purpose of this study is to evaluate the efficacy of ASF for patients with alcohol dependence. Methods: The effect of ASF will be studied in a randomized, double-blinded, placebo-controlled clinical trial. 82 outpatients and inpatients will be recruited and randomly assigned to treatment with either ASF or placebo for 6 weeks as a complement to cognitive behavioural therapy. The primary endpoints are the changes in the average daily alcohol consumption of the 2 groups before and after treatment and comparison of the scores of the psychological craving self-rating scale during the courses of treatment of 2 groups. The secondary endpoints include abstinence rates of the 2 groups during the follow-up period, days without consumption, and changes of Short Form Health Survey (SF-36) scores in 2 groups before and after therapy. Discussion: This study is the first randomized controlled trial to investigate ASF in the treatment of alcohol dependence. ASF is likely to be a new and effective drug for the treatment of alcohol dependence developed from natural products with a low incidence of side effects or toxicity. Trial Registration: Registry number: ChiCTR2000039397.

Background: COVID-19 is a globally emerging infectious disease. As the global epidemic continues to spread, the risk of COVID-19 transmission and diffusion in the world will also remain. Currently, several studies describing its clinical characteristics have focused on the initial outbreak, but rarely to the later stage. Here we described clinical characteristics, risk factors for disease severity and in-hospital outcome in patients with COVID-19 pneumonia from Wuhan. Methods: Patients with COVID-19 pneumonia admitted to Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology from February 13 to March 8, 2020, were retrospectively enrolled. Multivariable logistic regression analysis was used to identify risk factors for disease severity and in-hospital outcome and establish predictive models. Receiver operating characteristic (ROC) curve was used to assess the predictive value of above models.Results: 106 (61.3%) of the patients were female. The mean age of study populations was 62.0 years, of whom 73 (42.2%) had underlying comorbidities mainly including hypertension (24.9%). The most common symptoms on admission were fever (67.6%) and cough (60.1%), digestive symptoms (22.0%) was also very common. Older age (OR: 3.420; 95%Cl: 1.415-8.266; P=0.006), diarrhea (OR: 0.143; 95%Cl: 0.033-0.611; P=0.009) and lymphopenia (OR: 4.769; 95%Cl: 2.019-11.266; P=0.000) were associated with severe illness on admission; the area under the ROC curve (AUC) of predictive model were 0.860 (95%CI: 0.802-0.918; P=0.000). Older age (OR: 0.309; 95%Cl: 0.142-0.674; P=0.003), leucopenia (OR: 0.165; 95%Cl: 0.034-0.793; P=0.025), increased lactic dehydrogenase (OR: 0.257; 95%Cl: 0.100-0.659; P=0.005) and interleukins-6 levels (OR: 0.294; 95%Cl: 0.099-0.872; P=0.027) were associated with poor in-hospital outcome; AUC of predictive model were 0.752 (95%CI: 0.681-0.824; P=0.000).Conclusion: Older patients with diarrhea and lymphopenia need early identification and timely intervention to prevent the progression to severe COVID-19 pneumonia. However, older patients with leucopenia, increased lactic dehydrogenase and interleukins-6 levels are at a high risk for poor in-hospital outcome.Trial registration: ChiCTR2000029549

As the experiment neutrinoless double beta decay which can prove the Majarana quantum characteristic of neutrino goes into a technical problem of detection (the energy of neutrino is too small to distinguish from background radiation), ideas of newly designed experiment using neutrinos from single beta decay may solve the problem. This paper based on neutrinos released by beta radiation and photoelectric effect introduce a new experiment that could prove the Majarana quantum characteristic of neutrino.

Functional principal component analysis (FPCA) is a fundamental tool and has attracted increasing attention in recent decades, while existing methods are restricted to data with a single or finite number of random functions (much smaller than the sample size $n$). In this work, we focus on high-dimensional functional processes where the number of random functions $p$ is comparable to, or even much larger than $n$. Such data are ubiquitous in various fields such as neuroimaging analysis, and cannot be properly modeled by existing methods. We propose a new algorithm, called sparse FPCA, which is able to model principal eigenfunctions effectively under sensible sparsity regimes. While sparsity assumptions are standard in multivariate statistics, they have not been investigated in the complex context where not only is $p$ large, but also each variable itself is an intrinsically infinite-dimensional process. The sparsity structure motivates a thresholding rule that is easy to compute without nonparametric smoothing by exploiting the relationship between univariate orthonormal basis expansions and multivariate Kahunen-Lo\`eve (K-L) representations. We investigate the theoretical properties of the resulting estimators, and illustrate the performance with simulated and real data examples., Comment: 27 pages, 2 figures, 3 tables

SNAI1, an epithelial-mesenchymal transition (EMT)-inducing transcription factor, promotes tumor metastasis and resistance to apoptosis and chemotherapy. SNAI1 protein levels are tightly regulated by proteolytic ubiquitination. Here, we identified USP37 as a SNAI1 deubiquitinase that removes the polyubiquitination chain from SNAI1 and prevents its proteasomal degradation. USP37 directly binds, deubiquitinates, and stabilizes SNAI1. Overexpression of wild-type USP37, but not its catalytically inactive mutant C350S, promotes cancer cell migration. Importantly, depletion of USP37 downregulates endogenous SNAI1 protein and suppresses cell migration, which can be reversed by re-expression of SNAI1. Taken together, our findings suggest that USP37 is a SNAI1 deubiquitinase and a potential therapeutic target to inhibit tumor metastasis.

A high-efficient and low-cost catalyst on hydrogen isotope separation between hydrogen and water is an essential factor in industrial application for heavy water production and water detritiation. In past studies, Pt-based catalysts were developed but not practical for commercial use due to their high cost for vapor phase catalytic exchange (VPCE), while for impregnated nickel catalysts with a lower cost the problems of agglomeration and low Ni utilization existed. Therefore, to solve these problems, in-situ grown Ni-based catalysts (NiAl-LDO) derived from a layered double hydroxide (LDH) precursor were fabricated and first applied in VPCE in this work. Compared with traditional impregnated Ni-based catalysts, NiAl-LDO catalysts own a unique layered structure, homogeneous dispersed metallic phase, higher specific surface area as well as stronger metal-support interactions to prevent active metal from agglomerating. These advantages are beneficial for exposing more active sites to improve dynamic contacts between H2 and HDO in a catalyst surface and can bring excellent catalytic activity under a reaction temperature of lower than 400 &deg, C. Additionally, we found that the dissociative chemisorption of HDO and H2 occurs not only in Ni (111) but also in NiO species where chemisorbed H(ads), D(ads), OH(ads) and OD(ads) are formed. The results highlight that both of the Ni2+ species and Ni0 species possess catalytic activities for VPCE process.

Comparing to the commonly used hydraulic three-axial shaking tables, multi-degree of freedom shaking systems implemented by Stewart platform have the merits of being portable, easy to install and with high load capacity, but are not well studied because of the inherent nonlinearity and strong coupling of Stewart platform. In order to replicate multi-degree of freedom road acceleration spectrum on Stewart platform, analysis of the system was carried out. Firstly, the system structure was introduced and the linearized platform kinematic equations, at the equilibrium position, were inducted. The models of actuators that drive the platform were simplified and the principles of three variable controller (TVC) were deduced briefly. Finally, MATLAB-Adams co-simulation environment was built to perform multi-degree of freedom road acceleration spectrum replication with TVC. The results show that it can reproduce high accuracy multi-degree of freedom road acceleration spectrum with TVC on Stewart platform.

Geology, stratigraphy, drilling, logging, biomarker studies and apatite fission tracks were used to study Sinian- Ordovician mudstone and reservoir bitumen extracted from exploration wells located in central and southeastern Sichuan. This analysis confirms the source rocks were located in a reducing sedimentary environment, with organic matter such as bacteria and algae. The bitumen found in Sinian-Ordovician reservoirs in central Sichuan and Sinian reservoirs in southeastern Sichuan were mostly derived from Cambrian mudstones. The reservoir bitumen found in Cambrian rocks in southeastern Sichuan are from a mixed Cambrian-Silurian source. The apatite fission track combined with the Easy% Ro model were used to reconstruct the hydrocarbon-generation history of Cambrian source rocks in the Dingshan 1 well in southeastern Sichuan. The comparison between the Gaoke 1 well located in central Sichuan and the Dingshan 1 well demonstrates the maturation time and oil and gas generation stage from Cambrian source rocks in southeastern Sichuan is younger than the source rocks from central Sichuan. The source rock formations underwent tectonic uplift and reburial for secondary hydrocarbon-generation. The research methods provided can assist in oil exploration of deep and old hydrocarbon-bearing strata with a multi-stage evolution and tectonically superimposed features in the Chinese Qinghai-Tibet plateau basin, or similar basins worldwide.

Objective To observe the effect of Pingan Fang (PG) on behavioral sensitization and conditioned place preference (CPP) induced by ethanol in mice, and to determine the intervention mechanism of PG on alcohol addiction. Methods A behavioral sensitization mouse model induced by ethanol was established to observe the effect of PG on the development and expression of behavioral sensitization induced by ethanol by recording the spontaneous activity of mice. The resident time of mice in a white box was measured to evaluate the effect of PG on developing CPP induced by ethanol. Concentrations of dopamine (DA), Glutamate (Glu), and a-aminobutyric acid (GABA) in the corresponding mesolimbic region of mice were determined by enzyme-linked immunosorbent assay. Results Although PG did not alter spontaneous activity in mice, it reduced the growth of spontaneous activity stimulated by ethanol. The residence time in the white box after-ethanol-training of mice in CPP experiments was decreased. Conclusion Our data suggested that PG blocked the development and expression of behavioral sensitization induced by ethanol and the development of CPP in mice. The mechanism might be related to the decreased content of DA and Glu and increased content of GABA in the mesolimbic dopamine system. This suggests that PG might be useful for the prevention and treatment of alcohol addiction.

The performance of a Chinese lean iron ore as the oxygen carrier in chemical looping combustion was investigated in a fixed bed reactor. Considering the short contact time between the fuel gas and oxygen carrier in the sub-pilot experimental setup, the short injection time of CO was employed in the reactor to simulate this event. The injection time of CO was set to 60 s, 50 s and 40 s respectively, to investigate its effects on the reactivity of the oxygen carrier. A total of 100 cyclic reactions under each condition were carried out to test the reactivity stability of the oxygen carrier. The oxygen carriers prior and after reactions were characterized using SEM, XRD and BET. Results showed that there was an activation process of the reactivity during initial cycles. The extension of the reaction time was beneficial to the diffusion of CO into the oxygen carrier and could improve the conversion of CO. Also, it could form larger pore volumes for gas diffusion in the oxygen carrier. However, it led to the formation of the Fe2SiO4 and severe sintering on the surface, which was harmful to the stability of the oxygen carrier’s reactivity.

Caries is one of the most prevalent and costly infectious diseases affecting humans of all ages. It is initiated by cariogenic supragingival dental plaques forming on saliva-coated tooth surfaces, yet the etiology remains elusive. To determine which microbial populations may predispose a patient to caries, we report here an in-depth and comprehensive view of the microbial community associated with supragingival dental plaque collected from the healthy teeth of caries patients and healthy adults. We found that microbial communities from caries patients had a higher evenness and inter-individual variations but simpler ecological networks compared to healthy controls despite the overall taxonomic structure being similar. Genera including Selenomonas, Treponema, Atopobium, and Bergeriella were distributed differently between the caries and healthy groups with disturbed co-occurrence patterns. In addition, caries and healthy subjects carried different Treponema, Atopobium, and Prevotella species. Moreover, distinct populations of 13 function genes involved in organic acid synthesis, glycan biosynthesis, complex carbohydrate degradation, amino acid synthesis and metabolism, purine and pyrimidine metabolism, isoprenoid biosynthesis, lipid metabolism, and co-factor biosynthesis were present in each of the healthy and caries groups. Our results suggested that the fundamental differences in dental plaque ecology partially explained the patients' susceptibility to caries, and could be used for caries risk prediction in the future.

The classical Menon's identity [7] states that \begin{equation*}\label{oldbegin1} \sum_{\substack{a\in\Bbb Z_n^\ast }}\gcd(a -1,n)=\varphi(n) \sigma_{0} (n), \end{equation*} where for a positive integer $n$, $\Bbb Z_n^\ast$ is the group of units of the ring $\Bbb Z_n=\Bbb Z/n\Bbb Z$, $\gcd(\ ,\ )$ represents the greatest common divisor, $\varphi(n)$ is the Euler's totient function and $\sigma_{k} (n) =\sum_{d|n } d^{k}$ is the divisor function. In this paper, we generalize Menon's identity with Dirichlet characters in the following way: \begin{equation*} \sum_{\substack{a\in\Bbb Z_n^\ast b_1, ..., b_k\in\Bbb Z_n}} \gcd(a-1,b_1, ..., b_k, n)\chi(a)=\varphi(n)\sigma_k\left(\frac{n}{d}\right), \end{equation*} where $k$ is a non-negative integer and $\chi$ is a Dirichlet character modulo $n$ whose conductor is $d$. Our result can be viewed as an extension of Zhao and Cao's result [16] to $k>0$. It can also be viewed as an extension of Sury's result [12] to Dirichlet characters., Comment: 8 pages

For the purpose of study, based on the data provided by the United Nations Comtrade Database in 2006-2016, and using the trade competitive advantage index, trade intensity index and trade complementarity index, this paper made an empirical analysis on the development of agricultural trade between China and four South Asian countries. The results show that the scale of agricultural trade between China and the four South Asian countries was further expanded, but the growth rate was stable and the trade share declined, but the development potential of both sides has not been fully explored. Generally, China's agricultural products remain at a relatively disadvantaged position. Trade competitiveness and complementarity coexist. There is a large development potential and cooperation space for agricultural products trade between China and four South Asian countries.

The paper employs chaos theory in electric power system forecasting. The chaos prediction model is established via phase space reconstruction, and a new improved local prediction method is proposed and applied in micro-grid short-term load forecasting. Delay time and embedding dimension are calculated to reconstruct the phase space. The solved maximal Lyapunov exponent reveals the chaotic characteristics of the load time series, and the characteristic difference between the load time series and random series is analyzed through waveform comparison. Historical load data length and sampling interval of daily load are taken into consideration. Daily sampling intervals were taken as 15min, 30min, 45min and 60min, respectively. Finally, the model is applied to forecast actual load data of a certain community in Shaanxi province. Reasonable value range of the data length and sampling interval are given and the results can be taken as one reference for the optimal operation of the actual power grid.

Mastitis is one of most prevalent production disease in dairy herds worldwide, and is responsible for enormous economic losses. Heme oxygenase-1 (HO-1) is a cytoprotective enzyme, which is involved in the response to oxidative stress and inflammatory response. The purpose of this study was to detect the protective effect of HO-1 on LPS-induced mastitis in mice. BALB/c mice were pretreated with hemin (HO-1 inducer) and zinc protoporphyrin (ZnPP; HO-1 inhibitor) at 2h before LPS stimulation. The results showed that the mammary gland damage, production of inflammatory cytokines IL-1β, and MPO activity in mammary gland tissues were significantly reduced after pretreated with hemin compared with the group of LPS stimulation only. However, ZnPP reversed the effects of hemin. Furthermore, we found that the levels of ROS and NLRP3 inflammasome were increased after LPS stimulation. The increases were inhibited by hemin and the inhibition of hemin on ROS production and NLRP3 inflammasome activation were blocked by ZnPP. In addition, the results showed that hemin reduced the expression of thioredoxin-interacting protein (TXNIP) induced by LPS, and ZnPP attenuated these changes. In conclusion, the results suggested that overproduction of HO-1 may inhibit the activation of NLRP3 inflammasome and the expression of TXNIP. Induction of HO-1 may be served as a promising method against mastitis induced by LPS.

Inflammatory bone resorption mediated by osteoclasts is a major cause of morbidity and disability in many inflammatory disorders, including rheumatoid arthritis (RA). The mechanisms that regulate osteoclastogenesis and bone resorption in inflammatory settings are complex and have not been well elucidated. In this study, we identify the immunoregulator Def6 as a novel inhibitor of osteoclastogenesis in both physiological and inflammatory conditions. Def6 deficiency in Def6−/− mice enhanced the sensitivity of osteoclast precursors to the physiological osteoclastogenic inducer RANKL, and Def6−/− osteoclasts formed actin rings. Furthermore, Def6 deficiency markedly increased TNF-α-induced osteoclastogenesis both in vitro and in vivo and enhanced bone resorption in an inflammatory osteolysis mouse model. TNF-α serum levels negatively correlated with Def6 expression levels in osteoclast precursors obtained from RA patients and the osteoclastogenic capacity of the osteoclast precursors was significantly inversely correlated with their Def6 expression levels, indicating that Def6 functions as an inhibitor of excessive osteoclast formation and bone destruction in RA. Mechanistically, Def6 suppressed osteoclastogenesis and the expression of key osteoclastogenic factors NFATc1, Blimp1 and c-Fos by regulating an endogenous IFN-β mediated autocrine feedback loop. The Def6-dependent pathway may represent a novel therapeutic target to prevent pathological bone destruction.

Increased osteoclastogenesis is responsible for osteolysis, which is a severe consequence of inflammatory diseases associated with bone destruction, such as rheumatoid arthritis and periodontitis. The mechanisms that limit osteoclastogenesis under inflammatory conditions are largely unknown. We previously identified transcription factor RBP-J as a key negative regulator that restrains TNF-α-induced osteoclastogenesis and inflammatory bone resorption. In this study, we tested whether RBP-J suppresses inflammatory osteoclastogenesis by regulating the expression of microRNAs (miRNAs) important for this process. Using high-throughput sequencing of miRNAs, we obtained the first, to our knowledge, genome-wide profile of miRNA expression induced by TNF-α in mouse bone marrow-derived macrophages/osteoclast precursors during inflammatory osteoclastogenesis. Furthermore, we identified miR-182 as a novel miRNA that promotes inflammatory osteoclastogenesis driven by TNF-α and whose expression is suppressed by RBP-J. Downregulation of miR-182 dramatically suppressed the enhanced osteoclastogenesis program induced by TNF-α in RBP-J-deficient cells. Complementary loss- and gain-of-function approaches showed that miR-182 is a positive regulator of osteoclastogenic transcription factors NFATc1 and B lymphocyte-induced maturation protein-1. Moreover, we identified that direct miR-182 targets, Foxo3 and Maml1, play important inhibitory roles in TNF-α-mediated osteoclastogenesis. Thus, RBP-J-regulated miR-182 promotes TNF-α-induced osteoclastogenesis via inhibition of Foxo3 and Maml1. Suppression of miR-182 by RBP-J serves as an important mechanism that restrains TNF-α-induced osteoclastogenesis. Our results provide a novel miRNA-mediated mechanism by which RBP-J inhibits osteoclastogenesis and suggest that targeting of the newly described RBP-J-miR-182-Foxo3/Maml1 axis may represent an effective therapeutic approach to suppress inflammatory osteoclastogenesis and bone resorption.

Emerging concepts suggest that the functional phenotype of macrophages is regulated by transcription factors that define alternative activation states. We found that RBP-J, the main nuclear transducer of signaling via Notch receptors, augmented Toll-like receptor 4 (TLR4)-induced expression of key mediators of classically activated M1 macrophages and thus of innate immune responses to Listeria monocytogenes. Notch-RBP-J signaling controlled expression of the transcription factor IRF8 that induced downstream M1 macrophage-associated genes. RBP-J promoted the synthesis of IRF8 protein by selectively augmenting kinase IRAK2-dependent signaling via TLR4 to the kinase MNK1 and downstream translation-initiation control through eIF4E. Our results define a signaling network in which signaling via Notch-RBP-J and TLRs is integrated at the level of synthesis of IRF8 protein and identify a mechanism by which heterologous signaling pathways can regulate the TLR-induced inflammatory polarization of macrophages.

In this article, we obtain the central limit theorem and the law of the iterated logarithm for Galton-Watson processes in i.i.d. random environments.

There are three parts in this article. In Section 1, we establish the model of branching chain with drift in space-time random environment (BCDSTRE), i.e., the coupling of branching chain and random walk. In Section 2, we prove that any BCDSTRE must be a Markov chain in time random environment when we consider the distribution of the particles in space as a random element. In Section 3, we calculate the first-order moments and the second-order moments of BCDSTRE.

Glucagon-like peptide-1 (GLP-1) is a 30-amino acid peptide hormone, which has the regulatory function of stimulating the secretion of insulin to balance blood glucose levels. In this study, marker-free expression vector pX6 with a fusion gene of ten tandem repeated GLP-1 analog ([Ser8, Gln26 and Asp34]-GLP-1) genes was constructed and transformed into cucumbers by Agrobacterium tumefaciens-mediated transformation method. Four transgenic lines were obtained by PCR and Southern blotting analysis and two transgenic lines successfully expressed the fusion protein (named GLP-T), which was revealed by Western blotting analysis. The biological activity test results showed that the serum glucose level of diabetic rats was significantly decreased after oral administration of the fusion protein GLP-T extracted from the transgenic cucumber fruitage. These results suggest that this may provide a brand-new strategy to prevent and cure the diabetes with no pain.

In Section 1, the authors establish the models of two kinds of Markov chains in space-time random environments (MCSTRE and MCSTRE(+)) with abstract state space. In Section 2, the authors construct a MCSTRE and a MCSTRE(+) by an initial distribution Φ and a random Markov kernel (RMK) p(γ). In Section 3, the authors establish several equivalence theorems on MCSTRE and MCSTRE(+). Finally, the authors give two very important examples of MCMSTRE, the random walk in spce-time random environment and the Markov branching chain in space-time random environment.

This article is a continuation of [9]. Based on the discussion of random Kolmogorov forward (backward) equations, for any given q-matrix in random environment, Q(ϑ) = (q(ϑ;x,y),x,y ∈ χ), an infinite class of q-processes in random environments satisfying the random Kolmogorov forward (backward) equation is constructed. Moreover, under some conditions, all the q-processes in random environments satisfying the random Kolmogorov forward (backward) equation are constructed.

The concepts of Markov process in random environment, q-matrix in random environment, and q-process in random environment are introduced. The minimal q-process in random environment is constructed and the necessary and sufficient conditions for the uniqueness of q-process in random environment are given.

Objective: Overexpression of growth factor receptor-bound protein 7 (Grb7) has been found in numerous human cancers. The aim of this study was to evaluate the correlation between Grb7 gene amplification and protein expression in ovarian cancer (OC). Methods: We use Tissue Microarray (TMA) respectively to detect the gene amplification and protein expression of Grb7 in 90 cases OC and 10 control specimens of normal ovarian tissues by IHC and FISH. Results: The Grb7 protein expression by IHC analysis was observed in 52/90 (57.8%) OC with 3 cases (3.3%) scored 3+ and 9 cases (10%) scored 2+ Grb7 gene amplification by FISH analysis was successfully detectable in 6 specimens with a positive rate of 6.8% (6/88) in which immunostaining 3+, 2+ and negative (1+/0) expressions of Grb7 were 100.0% (3/3), 11.1% (1/9) and 2.6% (2/76), respectively. Our data exhibited that the IHC and FISH results had a good consistency between Grb7 gene amplification and Grb7 protein expression (Kappa = 0.651, P < 0.001). Both the results of IHC and FISH revealed that Grb7 did not seem to have a role in OC clinicopathology. Conclusion: There is a close relationship between Grb7 gene amplification and GRB7 protein overexpression in human OC. IHC might have limited diagnostic value especially in these tumors and especially in characterizing genetically diverse borderline cases, FISH could be superior to IHC.

The concepts of Markov process in random environment,q-matrix in random environment andq-process in random environment are introduced. Three forms of random Kolmoogrov farward (or backward) equations are introduced and the equivalence of these three forms are also proved. Moreover any conservativeq-process in random environment satisfies random Kolmogrov backward equation.

The operating voltage of an aluminum electrolytic capacitor is determined by the breakdown voltage (Ub) of the Al2O3 anode. Ub is related to the molecular adsorption at the Al2O3/electrolyte interface. Therefore, we have employed sum-frequency vibrational spectroscopy (SFVS) to study the adsorption states of a simple electrolyte, ethylene glycol (EG) solution with ammonium adipate, on an α-Al2O3 surface. In an acidic electrolyte (pH < 6), the Al2O3 surface is positively charged. The observed SFVS spectra show that long chain molecules poly ethylene glycol and ethylene glycol adipate adopt a “lying” orientation at the interface. In an alkaline electrolyte (pH > 8), the Al2O3 surface is negatively charged and the short chain EG molecules adopt a “tilting” orientation. The Ub results exhibit a much higher value at pH < 6 compared with that at pH > 8. Since the “lying” long chain molecules cover and protect the Al2O3 surface, Ub increases with a decrease of pH. These findings provide new insights to study the breakdown mechanisms and to develop new electrolytes for high operating voltage capacitors.

We introduce the results on the multifractal structure of the occupation measures of a Brownian Motion, a stable process, a general subordinator and a stochastic process derived from random reordering of the Cantor set. We also introduced an interesting and powerful technique to investigate the multifractal spectrum.

In this paper we have found a general subordinator,X, whose range up to time 1,X([0, 1)), has similar structure as random re-orderings of the Cantor setK(ω).X([0, 1)) andK(ω) have the same exact Hausdorff measure function and the integal test of packing measure.

26 páginas, 10 figuras, 1 tabla.-- El documento en word es la versión post-print del artículo., The fungal analog zymosan induces IL-23 and low amounts of IL-12 p70. This study addresses the molecular mechanisms underlying this cytokine pattern in human monocyte-derived dendritic cells. The transcriptional regulation of il23a, one of the chains of IL-23, depended on the activation of c-Rel and histone H3 phosphorylation, as judged from the association of c-Rel with the il23a promoter and the correlation between IL-23 production and S10-histone H3 phosphorylation. Consistent with its reduced ability to produce IL-12 p70, zymosan induced a transient occupancy of the il12a promoter by c-Rel, blocked the production of IL-12 p70 and the transcription of il12a induced by other stimuli, and triggered the expression and nuclear translocation of the transcriptional repressors of the Notch family hairy and enhancer of split (Hes)-1, Hes5, hairy/enhancer-of-split related with YRPW motif protein (Hey)-1, and TLE (transducin-like enhancer of split). Zymosan also induced the interaction of Hes1 and TLE with histone H3 phosphorylated on S10 and deacetylated on K14. Inhibition of class III histone deacetylases increased the production of IL-12 p70 and partially blunted the inhibitory effect of zymosan on the production of IL-12 p70 elicited by LPS and IFN-γ. These results indicate that the selective induction of IL-23 byβ-glucans is explained by the activation of c-Rel associated with S10-histone H3 phosphorylation in the il23a promoter mediated by mitogen- and stress-activated kinase (MSK) and/or protein kinase A, and inhibition of il12a transcription by a mechanism involving activation of several corepressors with ability to bind TLE and to promote histone deacetylation.

Positive regulation of cell migration by chemotactic factors and downstream signaling pathways has been extensively investigated. In contrast, little is known about factors and mechanisms that induce migration arrest, a process important for retention of cells at inflammatory sites and homeostatic regulation of cell trafficking. In this study, we found that IFN-gamma directly inhibited monocyte migration by suppressing remodeling of the actin cytoskeleton and cell polarization in response to the chemokine CCL2. Inhibition was dependent on STAT1 and downstream genes, whereas STAT3 promoted migration. IFN-gamma altered monocyte responses to CCL2 by modulating the activity of Pyk2, JNK, and the GTPases Rac and Cdc42, and inhibiting CCL2-induced activation of the downstream p21-activated kinase that regulates the cytoskeleton and cell polarization. These results identify a new role for IFN-gamma in arresting monocyte chemotaxis by a mechanism that involves modulation of cytoskeleton remodeling. Crosstalk between Jak-STAT and Rac/Cdc42 GTPase-mediated signaling pathways provides a molecular mechanism by which cytokines can regulate cell migration.

To achieve high system capacity over frequency-selective fading channel, multi-carrier code-division-multiple-access (MC-CDMA) system with spatial diversity using space-time block coding (STBC) is considered. We present a subspace-based semi-blind channel estimation method under multiuser environment to resolve the inherent scalar ambiguity when blind estimation technique is used. Mean-square-error (MSE) expression for the proposed channel estimation technique is derived. Bit-error-rate (BER) when using linear zero-forcing (ZF) and minimum-mean-square-error (MMSE) multiuser detection techniques taking the channel estimation error into consideration are obtained through simulation. The correctness of the BERs is further verified through estimating the signal-to-interference and noise-ratio (SINR) at the multiuser detectors.

A double chopper-stabilized analog front-end (DCS-AFE) circuit for a thermopile sensor is presented, which includes a closed-loop front-end amplifier and a 2nd-order 1 bit quantization sigma-delta modulator. The amplifier with a closed-loop structure ensures the gain stability against the temperature. Moreover, by adopting the chopper-stabilized technique both for the amplifier and 2nd-order 1-bit quantization sigma-delta modulator, the low-frequency 1/f noise and offset is reduced and high resolution is achieved. The AFE is implemented in the SMIC 0.18 μm 1P6M CMOS process. The measurement results show that in a 3.3 V power supply, 1 Hz input frequency and 3KHz clock frequency, the peak signal-to-noise and distortion ratio (SNDR) is 55.4 dB, the effective number of bits (ENOB) is 8.92 bit, and in the range of -20 to 85 degrees, the detection resolution is 0.2 degree.

A low-power, configurable auto-gain control loop for a digital hearing aid system on a chip (SoC) is presented. By adopting a mixed-signal feedback control structure and peak detection and judgment, it can work in automatic gain or variable gain control modes through a digital signal processing unit. A noise-reduction and dynamic range (DR) improvement technique is also used to ensure the DR of the circuit in a low-voltage supply. The circuit is implemented in an SMIC 0.13 μm 1P8M CMOS process. The measurement results show that in a 1 V power supply, 1.6 kHz input frequency and 200 mVp—p, the SFDR is 74.3 dB, the THD is 66.1 dB, and the total power is 89 μW, meeting the application requirements of hearing aid SoCs.

Macrophage polarization is accompanied by drastic changes of L-arginine metabolism. Two L-arginine catalytic enzymes, iNOS and arginase 1, are well-characterized hallmark molecules of M(IFN-γ) and M(IL-4) polarization, respectively. The third metabolic fate of L-arginine is generation of creatine that acts as a key source of cellular energy reserve, whereas little is known about regulation and function of creatine metabolism in the immune system. Here, combination of genetic, genomic, metabolic, and immunological analyses revealed that creatine fundamentally reprogrammed macrophage polarization by suppressing M(IFN-γ) yet promoting M(IL-4) effector functions. Mechanistically, creatine inhibited IFN-γ-JAK-STAT1-mediated induction of immune effector molecules including iNOS while supported IL-4-triggered STAT6-dependent upregulation of arginase 1. Depletion of intracellular creatine by ablation of creatine transporter Slc6a8 significantly altered macrophage-mediated immune responses in vivo. These results depicted a previously uncharacterized regulatory loop whereby creatine, a single cellular metabolite, shaped macrophage polarization by regulating L-arginine metabolic enzymes.