Search

Abstract This paper introduces an adaptive control scheme for quadrotor suspended load systems, to track desired trajectory with variable payload and wind disturbances. The dynamic model of the quadrotor suspended load system is developed, taking into account the impact of the wind field described by the Dryden model. To attenuate the effects of payload variation and wind disturbances on the system, an adaptive control method based on disturbance observers is devised. Additionally, the uniform boundedness of all error signals is demonstrated. The effectiveness of the designed control method is verified through simulations, which serves to strengthen its applicability in practical applications.

Abstract Prolactin (PRL) is a polypeptide hormone that is mainly synthesized and secreted by the lactotroph cells of the pituitary. There are two main isoforms of PRL: 23‐kDa PRL (named full‐length PRL) and vasoinhibins (including 5.6–18 kDa fragments). Both act as circulating hormones and cytokines to stimulate or inhibit vascular formation at different stages and neovascularization, including endothelial cell proliferation and migration, protease production, and apoptosis. However, their effects on vascular function and cardiovascular diseases are different or even contrary. In addition to the structure, secretion regulation, and signal transduction of PRL/vasoinhibins, this review focuses on the pathological mechanism and clinical significance of PRL/vasoinhibins in cardiovascular diseases.

This study investigates the adaptive fuzzy output feedback control of strict-feedback fractional-order chaotic systems with unmeasurable states and quantized input. First, the functional uncertainties are approximated by fuzzy logic systems (FLSs). Second, combining the FLS and the system output signal, an observer is constructed to estimate the unmeasurable states. A command filter is defined to cope with the “explosion of complexity” problem resulting from the repeated derivatives of virtual control inputs in each backstepping step. To compensate for quantization errors, a hyperbolic tangent function is introduced to transform the control signal, which can not only guarantee that the tracking error converges to an arbitrarily small region near the origin but also reduce the chattering phenomenon of the control input. In addition, the stability analysis is carried out relying on the fractional Lyapunov stability criterion such that all the signals keep bounded. Finally, a numerical simulation example is put forward to verify the effectiveness of our method.

Objectives The aim was to elucidate the relationship between liver function and idiopathic pulmonary arterial hypertension (IPAH).Design and setting Retrospective, longitudinal study in urban tertiary care centre in Shanghai, China.Participants 407 IPAH consecutive incident patients age 18–65 years were retrospectively enrolled from January 2008 to December 2018.Outcome measurements The primary endpoint was all-cause mortality. The cut-off value was determined by receiver operating characteristic curve (ROC), which was validated by Cox proportional hazard model was internally validated by bootstrap analysis and used for survival analysis. The Cox model was (internally) validated and cross-validated areas under the curve (AUC) should be reported.Results The prevalence of abnormal liver function tests (LFTs) at baseline was 77.6%. Hyperbilirubinaemia is the most common abnormal biochemical liver test: abnormal total bilirubin (TBIL in 51.6% patients). During the follow-up, 160 patients died. Patients with mixed liver dysfunction have worse prognosis than those with normal LFTs or isolated abnormal bilirubin metabolism. Comparing with patients with hepatocellular injury, the survival of patients with abnormal bilirubin metabolism is lower. Multivariable Cox models revealed a positive association between TBIL, γ-glutamyltransferase (GGT) and mortality showing that each Ig increment in TBIL and GGT was associated with a higher all-cause mortality (TBIL: HR 4. 29 (95% CI 1. 21 to 15. 27), p=0. 02; GGT: HR 2. 76 (95% CI 1. 18 to 6. 45), p=0. 02). A novel formula named Liver Function Predict Index (LFPI) was constructed (LFPI=−0.002*6MWD+1.014*lg GGT+1.458*lg TBIL) to predict prognosis. ROC curve analysis did further identify 2.729 as the best cut-off value for LFPI (AUC 0.75, p

Abstract The re-emerging human adenovirus types HAdV7, HAdV14, and HAdV55 of species B have caused severe lower respiratory tract diseases and even deaths during recent outbreaks. However, no adenovirus vaccine or therapeutic has been approved for general use. These adenoviruses attach to host cells via the knob domain of the fiber, using human desmoglein 2 as the primary cellular receptor. In this study, a recombinant HAdV11 fiber knob trimer (HAdV11FK) expressed in E. coli was shown to induce broadly neutralizing antibodies against HAdV11, -7, -14p1, and -55 in mice. Using HAdV11FK as an antigen, three monoclonal antibodies, 6A7, 3F11, and 3D8, with high neutralizing activity were generated. More importantly, the results of in vitro neutralization assays demonstrated that 3F11 and 3D8 cross-neutralized HAdV11, -7, and -55, but not HAdV14p1. The amino acids 251KE252 within the F-G loop may be the crucial amino acids in the conformational epitope recognized by 3F11, which is common to HAdV11, -7, -14p, and -55, but is not present in HAdV14p1 and HAdV3. A two-amino-acid deletion in the HAdV14p1 structure breaks the short alpha helix (248SREKE252) that is present in the HAdV7, -11, -55, and -14p fiber knob structures. Our findings add to the knowledge of adenovirus fiber structure and antibody responses and are important for the design of adenovirus vaccines and antiviral drugs with broad activity.

Investigating fitness interactions in natural populations remains a considerable challenge. We take advantage of the unique population structure of Vibrio parahaemolyticus, a bacterial pathogen of humans and shrimp, to perform a genome-wide screen for coadapted genetic elements. We identified 90 interaction groups (IGs) involving 1,560 coding genes. 82 IGs are between accessory genes, many of which have functions related to carbohydrate transport and metabolism. Only 8 involve both core and accessory genomes. The largest includes 1,540 SNPs in 82 genes and 338 accessory genome elements, many involved in lateral flagella and cell wall biogenesis. The interactions have a complex hierarchical structure encoding at least four distinct ecological strategies. One strategy involves a divergent profile in multiple genome regions, while the others involve fewer genes and are more plastic. Our results imply that most genetic alliances are ephemeral but that increasingly complex strategies can evolve and eventually cause speciation.

Human adenovirus type 4 (HAdV-4) is an epidemic virus that contributes to serious acute respiratory disease (ARD) in both pediatric and adult patients. However, no licensed drug or vaccine is currently available to the civilian population. The identification of neutralizing epitopes of HAdV-4 should allow the development of a novel antiviral vaccine and a novel gene transfer vector, and an effective neutralizing monoclonal antibody (MAb) will be useful in developing appropriate antiviral drugs. In this study, we report that MAb MN4b shows strong neutralizing activity against HAdV-4. MN4b recognizes a conformational epitope (418AGSEK422) within hypervariable region 7 (HVR7). Mutations within this site permitted HAdV-4 mutants to escape neutralization by MN4b and to resist neutralization by animal and human anti-HAdV-4 sera. A recombinant virus, rAd3-A4R7-1, containing the identified neutralizing epitope in the HVR7 region of HAdV-3 hexon, successfully induced antiserum that inhibited HAdV-4 infection. These results indicate that a small surface loop of HAdV-4 hexon is a critical neutralization epitope for this virus. The generation of MN4b and the identification of this neutralizing epitope may be useful in developing therapeutic treatment, a subunit vaccine, and a novel vector that can escape preexisting neutralization for HAdV-4. IMPORTANCE Neutralizing antibodies are considered good tools for the prevention of human adenovirus type 4 (HAdV-4) infections. The identification of the epitopes recognized by such neutralizing antibodies is important for the generation of recombinant antiviral vaccines. However, until now, no neutralizing epitope has been reported for HAdV-4. Here, we developed a serotype-specific neutralizing MAb directed against HAdV-4, MN4b. We provide evidence that MN4b recognizes a conformational epitope within HVR7 of HAdV-4 hexon. Antisera generated to this conformational epitope displayed on HAdV-3 hexon inhibited infection of AD293 cells by HAdV-4. Our findings are very important for the development of therapeutic treatment, a subunit vaccine, and a novel vector for HAdV-4. [ABSTRACT FROM AUTHOR]

Nonsense-mediated mRNA decay (NMD), also called RNA surveillance, is a process that degrades mRNAs with premature translation termination codons. In Saccharomyces cerevisiae, it has also been shown that NMD can regulate gene expression at the transcriptional level. To date, there has been no example where promoters are regulated by the NMD path-way in higher eukaryotes. Taking advantage of our previous research on ZNF268 transcription control, we studied the relationship between the ZNF268 promoter and the NMD pathway. We showed by transient transfection that the ZNF268 promoter activity was influenced by hUpf1, not hSmg6, in HeLa cells. This result was confirmed by the analysis of the steady state mRNA of ZNF268 after depletion of endogenous hUpf1 or hSmg6 in HeLa cells. Direct mutational analysis revealed that the C/EBP site in the promoter region is important for hUpf1 function on ZNF268 promoter. Together our results demonstrated that the mammalian gene ZNF268 is regulated by hUpf1 via its promoter. [ABSTRACT FROM AUTHOR]

Human adenovirus types 3 and 7 (HAdV-3 and HAdV-7) occur epidemically and contribute greatly to respiratory diseases, but there is no currently available licensed recombinant HAdV-3/HAdV-7 bivalent vaccine. Identification of serotype-specific neutralizing antibody (NAb) epitopes for HAdV-3 and HAdV-7 will be beneficial for development of recombinant HAdV-3/HAdV-7 bivalent vaccines. In this study, four NAb epitopes within hexon hypervariable regions (HVRs) were predicted for HAdV-3 and HAdV-7, respectively, by using bioinformatics. Eight hexon chimeric adenovirus vectors with the alternation of only one predicted neutralizing epitope were constructed. Further in vitro and in vivo neutralization assays indicated that E2 (residing in HVR2) and E3 (residing in HVR5) are NAb epitopes for HAdV-7, and E3 plays a more important role in generating NAb responses. Cross-neutralization assays indicated that all four predicted epitopes, R1 to R4, are NAb epitopes for HAdV-3, and R1 (residing in HVR1) plays the most important role in generating NAb responses. Humoral immune responses elicited by the recombinant rAdH7R1 (containing the R1 epitope) were significantly and durably suppressed by HAdV-3-specific NAbs. Surprisingly, the rAdΔE3GFP-specific neutralizing epitope responses induced by rAdMHE3 (R3 replaced by E3) and rAdMHE4 (R4 replaced by E4) were weaker than those of rAdMHE1 (R1 replaced by E1) or rAdMHE2 (R2 relaced by E2) in vitro and in vivo. Furthermore, rAdMHE4 replicated more slowly in HEp-2 cells, and the final yield was about 10-fold lower than that of rAdΔE3GFP. The current findings contribute not only to the development of new adenovirus vaccine candidates, but also to the construction of new gene delivery vectors. [ABSTRACT FROM AUTHOR]