A simple stochastic nonlinear AR model with application to bubble

Economic and financial time series can feature locally explosive behavior when a bubble is formed. The economic or financial bubble, especially its dynamics, is an intriguing topic that has been attracting longstanding attention. To illustrate the dynamics of the local explosion itself, the paper presents a novel, simple, yet useful time series model, called the stochastic nonlinear autoregressive model, which is always strictly stationary and geometrically ergodic and can create long swings or persistence observed in many macroeconomic variables. When a nonlinear autoregressive coefficient is outside of a certain range, the model has periodically explosive behaviors and can then be used to portray the bubble dynamics. Further, the quasi-maximum likelihood estimation (QMLE) of our model is considered, and its strong consistency and asymptotic normality are established under minimal assumptions on innovation. A new model diagnostic checking statistic is developed for model fitting adequacy. In addition two methods for bubble tagging are proposed, one from the residual perspective and the other from the null-state perspective. Monte Carlo simulation studies are conducted to assess the performances of the QMLE and the two bubble tagging methods in finite samples. Finally, the usefulness of the model is illustrated by an empirical application to the monthly Hang Seng Index.Comment: 41 pages, 6 figure

Novel TLR7/8 agonists promote activation of HIV-1 latent reservoirs and human T and NK cells

Antiretroviral therapy can successfully suppress HIV-1 replication to undetectable levels but fails to eliminate latent and persistent HIV-1 reservoirs. Recent studies have focused on the immunomodulatory agents such as Toll-like receptor 7 and 8 (TLR7 and TLR8) capable of activating, thereby rendering the reservoir susceptible to antiretroviral inhibition and immune recognition and elimination. In this context, this study focused on generating a diverse repertoire of TLR7/8 agonists to identify more potent candidates for activating latent HIV-1 and immune cells’ response. Through combinational strategies of computer-aided design and biological characterization, 159 pyrido [3,2-d] pyrimidine and pyridine-2-amine-based derivatives were synthesized. Of which, two TLR7/8 dual and one TLR8-specific agonists with exceptionally high potency in activating HIV-1 latent reservoirs in cell lines and PBMCs of patients with persistent and durable virologic controls were identified. Particularly, these agonists appeared to enhance NK and T cells activity, which were correlated with the degree of surface activation markers. The outcome of this study highlights the remarkable potential of TLR7/8 agonists in simultaneously activating HIV-1 from the latently infected cells and augmenting immune effector cells

Recruitment of a SAP18-HDAC1 Complex into HIV-1 Virions and Its Requirement for Viral Replication

HIV-1 integrase (IN) is a virally encoded protein required for integration of viral cDNA into host chromosomes. INI1/hSNF5 is a component of the SWI/SNF complex that interacts with HIV-1 IN, is selectively incorporated into HIV-1 (but not other retroviral) virions, and modulates multiple steps, including particle production and infectivity. To gain further insight into the role of INI1 in HIV-1 replication, we screened for INI1-interacting proteins using the yeast two-hybrid system. We found that SAP18 (Sin3a associated protein 18 kD), a component of the Sin3a-HDAC1 complex, directly binds to INI1 in yeast, in vitro and in vivo. Interestingly, we found that IN also binds to SAP18 in vitro and in vivo. SAP18 and components of a Sin3A-HDAC1 complex were specifically incorporated into HIV-1 (but not SIV and HTLV-1) virions in an HIV-1 IN–dependent manner. Using a fluorescence-based assay, we found that HIV-1 (but not SIV) virion preparations harbour significant deacetylase activity, indicating the specific recruitment of catalytically active HDAC into the virions. To determine the requirement of virion-associated HDAC1 to HIV-1 replication, an inactive, transdominant negative mutant of HDAC1 (HDAC1H141A) was utilized. Incorporation of HDAC1H141A decreased the virion-associated histone deacetylase activity. Furthermore, incorporation of HDAC1H141A decreased the infectivity of HIV-1 (but not SIV) virions. The block in infectivity due to virion-associated HDAC1H141A occurred specifically at the early reverse transcription stage, while entry of the virions was unaffected. RNA-interference mediated knock-down of HDAC1 in producer cells resulted in decreased virion-associated HDAC1 activity and a reduction in infectivity of these virions. These studies indicate that HIV-1 IN and INI1/hSNF5 bind SAP18 and selectively recruit components of Sin3a-HDAC1 complex into HIV-1 virions. Furthermore, HIV-1 virion-associated HDAC1 is required for efficient early post-entry events, indicating a novel role for HDAC1 during HIV-1 replication

Local Resistance in Early Medieval Chinese Historiography and the Problem of Religious Overinterpretation

Official Chinese historiography is a treasure trove of information on local resistance to the centralised empire in early medieval China (third to sixth century). Sinologists specialised in the study of Chinese religions commonly reconstruct the religious history of the era by interpreting some of these data. In the process, however, the primary purpose of the historiography of local resistance is often overlooked, and historical interpretation easily becomes ‘overinterpretation’—that is, ‘fabricating false intensity’ and ‘seeing intensity everywhere’, as French historian Paul Veyne proposed to define the term. Focusing on a cluster of historical anecdotes collected in the standard histories of the four centuries under consideration, this study discusses the supposedly ‘religious’ nature of some of the data they contain

Free Vibration Analysis of a Spinning Composite Laminated Truncated Conical Shell under Hygrothermal Environment

This paper is concerned with free vibration characteristics of a spinning composite laminated truncated conical shell subjected to hygrothermal environment. Hygrothermal strains are introduced into the constitutive law of single-layer material, and fiber orientation lies symmetrically with respect to the midplane of the composite shell. Considering the spin-induced Coriolis and centrifugal forces, as well as initial hoop tension, the governing equations of free vibration of the composite conical shell with hygrothermal effects are derived on the basis of Love’s thin-shell theory and Hamilton’s principle. The solution of the equations is derived using the Galerkin approach. Then, a detailed parametric study on natural frequencies and critical spinning speeds is numerically performed. Results indicate that the Coriolis force induces an asymmetric influence on natural frequencies of forward and backward traveling waves, while the centrifugal force enhances the frequencies of both traveling waves symmetrically. Initial hoop tension plays a major role in the increase of critical spinning angular speed. Temperature, moisture concentration, and design parameters show the significant influence on the free vibration characteristics of the conical shell, and thermal expansion deformation is nonnegligible in the free vibration analysis

Free Vibration Analysis of a Spinning Composite Laminated Truncated Conical Shell under Hygrothermal Environment

This paper is concerned with free vibration characteristics of a spinning composite laminated truncated conical shell subjected to hygrothermal environment. Hygrothermal strains are introduced into the constitutive law of single-layer material, and fiber orientation lies symmetrically with respect to the midplane of the composite shell. Considering the spin-induced Coriolis and centrifugal forces, as well as initial hoop tension, the governing equations of free vibration of the composite conical shell with hygrothermal effects are derived on the basis of Love’s thin-shell theory and Hamilton’s principle. The solution of the equations is derived using the Galerkin approach. Then, a detailed parametric study on natural frequencies and critical spinning speeds is numerically performed. Results indicate that the Coriolis force induces an asymmetric influence on natural frequencies of forward and backward traveling waves, while the centrifugal force enhances the frequencies of both traveling waves symmetrically. Initial hoop tension plays a major role in the increase of critical spinning angular speed. Temperature, moisture concentration, and design parameters show the significant influence on the free vibration characteristics of the conical shell, and thermal expansion deformation is nonnegligible in the free vibration analysis

Advances in Disease-Modifying Therapy of Neuromyelitis Optic Spectrum Disorders

Neuromyelitis optic spectrum disorders (NMOSD) is a serious inflammatory demyelinating disease. Clinical treatment of NMOSD mainly involves acute phase treatment and remission phase prevention treatment. Disease-modifying therapy (DMT) in remission phase of NMOSD can effectively reduce disease recurrence and delay disability progression. At present, the drugs commonly used for DMT at home and abroad include classical immunosuppression, B-cell surface antigen monoclonal antibody, complement targeting monoclonal antibody, IL-6 receptor-targeting monoclonal antibody, etc. This paper mainly reviews the DMT drugs efficacy, safety, as well as the marketing status of NMOSD

Antibodies and vaccines against Middle East respiratory syndrome coronavirus

ABSTRACTThe Middle East respiratory syndrome coronavirus (MERS-CoV) has spread through 27 countries and infected more than 2,200 people since its first outbreak in Saudi Arabia in 2012. The high fatality rate (35.4%) of this novel coronavirus and its persistent wide spread infectiousness in animal reservoirs have generated tremendous global public health concern. However, no licensed therapeutic agents or vaccines against MERS-CoV are currently available and only a limited few have entered clinical trials. Among all the potential targets of MERS-CoV, the spike glycoprotein (S) has been the most well-studied due to its critical role in mediating viral entry and in inducing a protective antibody response in infected individuals. The most notable studies include the recent discoveries of monoclonal antibodies and development of candidate vaccines against the S glycoprotein. Structural characterization of MERS-CoV S protein bound with these monoclonal antibodies has provided insights into the mechanisms of humoral immune responses against MERS-CoV infection. The current review aims to highlight these developments and discuss possible hurdles and strategies to translate these discoveries into ultimate medical interventions against MERS-CoV infection

DgHDA6 enhances the cold tolerance in chrysanthemum by improving ROS scavenging capacity

Histone deacetylases have been demonstrated to play an important role in responding to low-temperature stress, but the related response mechanism in chrysanthemum remains unclear. In this study, we isolated a cold-induced gene, DgHDA6, from chrysanthemum (Chrysanthemum morifolium Ramat). DgHDA6 contains 474 amino acids and shares a typical deacetylation domain with RPD3/HDA1 family members. The overexpression of DgHDA6 enhanced cold resistance in chrysanthemums. After low-temperature stress, the overexpression lines showed a higher survival rate. The contents of proline, soluble proteins and sugars, and the activities of antioxidant enzymes were significantly increased while the contents of H2O2, O2− and MDA were lower. Moreover, cold-stress-responding genes such as DgCuZnSOD, DgCAT, DgP5CS, and DgFAD were upregulated after cold stress. These results suggest that the overexpression of DgHDA6 can improve cold tolerance in chrysanthemum by enhancing ROS scavenging capacity