New Approach to Develop Ultra-High Inhibitory Drug Using the Power Function of the Stoichiometry of the Targeted Nanomachine or Biocomplex

AIMS: To find methods for potent drug development by targeting to biocomplex with high copy number. METHODS: Phi29 DNA packaging motor components with different stoichiometries were used as model to assay virion assembly with Yang Hui\u27s Triangle [Formula: see text], where Z = stoichiometry, M = drugged subunits per biocomplex, p and q are the fraction of drugged and undrugged subunits in the population. RESULTS: Inhibition efficiency follows a power function. When number of drugged subunits to block the function of the complex K = 1, the uninhibited biocomplex equals q(z), demonstrating the multiplicative effect of stoichiometry on inhibition with stoichiometry 1000 \u3e 6 \u3e 1. Complete inhibition of virus replication was found when Z = 6. CONCLUSION: Drug inhibition potency depends on the stoichiometry of the targeted components of the biocomplex or nanomachine. The inhibition effect follows a power function of the stoichiometry of the target biocomplex

Performance evaluation of a tidal current turbine with bidirectional symmetrical foils

As one might expect, tidal currents in terms of ebb and flood tides are approximately bidirectional. A Horizontal Axial Tidal Turbine (HATT) with unidirectional foils has to be able to face the current directions in order to maximize current energy harvesting. There are two regular solutions to keep a HATT always facing the direction of the flow, which are transferred from wind turbine applications. One is to yaw the turbine around the supporting structure with a yaw mechanism. The other is to reverse the blade pitch angle through 180° with a pitch-adjusting mechanism. The above solutions are not cost-effective in marine applications due to the harsh marine environment and high cost of installation and maintenance. In order to avoid the above disadvantages, a turbine with bidirectional foils is presented in this paper. A bare turbine with bidirectional foils is characterized in that it has nearly the same energy conversion capability in both tidal current directions without using the yaw or pitch mechanism. Considering the working conditions of the bidirectional turbine in which the turbine is installed on a mono-pile, the effect of the mono-pile on the turbine’s performance is evaluated in this paper, especially when the turbine is downstream of the mono-pile. The paper was focused on the evaluation of the hydrodynamic performance of the bidirectional turbine. The hydrodynamic performance of the bare bidirectional turbine without any supporting structure was evaluated based on a steady-state computational fluid dynamics (CFD) model and model tests. Performance comparison has been made between the turbine with bidirectional foils and the turbine with NACA foils. The effect of the mono-pile on the performance of the bidirectional turbine was studied by using the steady-state and the transient CFD model. The steady-state CFD model was used to evaluate the effect of the mono-pile clearance, which is the distance between the mono-pile and the turbine on the performance of the turbine. The transient CFD model was used to determine the time-dependent characteristics of the turbine, such as time-dependent power and drag coefficients. The results show that the bare bidirectional turbine has nearly the same energy conversion capability in both tidal current directions. The performance of the bidirectional turbine is inferior to the turbine with NACA foils. At the designed tip speed ratio, the power coefficient of the turbine with NACA foils is 0.4498, which increases by 1.6% compared to the 0.4338 of the bidirectional turbine. The turbine’s performance decreases due to the introduction of the mono-pile, and the closer the turbine is to the mono-pile, the greater effect on the turbine’s performance the mono-pile has. At the designed clearance of 1.5 DS, the presence of a mono-pile decreases the peak Cp value by 1.82% and 3.17% to a value of 0.4156 and 0.4004 for the turbine located in the mono-pile upstream and downstream, respectively. The mono-pile can result in the fluctuation of the turbine’s performance. This fluctuation will detrimentally harm the life of the turbine as it will lead to increased wear and fatigue issues

Security Proof of JAMBU under Nonce Respecting and Nonce Misuse Cases

JAMBU is an AEAD mode of operation which entered the third round of CAESAR competition. However, it does not have a security proof like other modes of operation do, and there was a cryptanalysis result that has overthrown the security claim under nonce misuse case by the designers. In this paper, we complement the shortage of the scheme by giving security proofs of JAMBU both under nonce respecting case and nonce misuse case. We prove that JAMBU under nonce respecting case has a slightly lower security than the birthday bound of $n$ bits, and JAMBU under nonce misuse case has a tight security bound of $n/2$ bits

VPA mediates bidirectional regulation of cell cycle progression through the PPP2R2A-Chk1 signaling axis in response to HU

Cell cycle checkpoint kinases play a pivotal role in protecting against replicative stress. In this study, valproic acid (VPA), a histone deacetylase inhibitor (HDACi), was found to promote breast cancer MCF-7 cells to traverse into G2/M phase for catastrophic injury by promoting PPP2R2A (the B-regulatory subunit of Phosphatase PP2A) to facilitate the dephosphorylation of Chk1 at Ser317 and Ser345. By contrast, VPA protected normal 16HBE cells from HU toxicity through decreasing PPP2R2A expression and increasing Chk1 phosphorylation. The effect of VPA on PPP2R2A was at the post-transcription level through HDAC1/2. The in vitro results were affirmed in vivo. Patients with lower PPP2R2A expression and higher pChk1 expression showed significantly worse survival. PPP2R2A D197 and N181 are essential for PPP2R2A-Chk1 signaling and VPA-mediated bidirectional effect on augmenting HU-induced tumor cell death and protecting normal cells

Pickering emulsion-enhanced interfacial biocatalysis: tailored alginate microparticles act as particulate emulsifier and enzyme carrier

A robust Pickering emulsion stabilized by lipase-immobilized alginate gel microparticles with a coating of silanized titania nanoparticles is developed for biphasic biocatalysis. The good recyclability and high stability of the proposed interfacial catalysis system have been verified, retaining about 90% of relative enzyme activity in 10 catalytic cycles with operation for 240 h. Meanwhile the Pickering emulsions remain stable during a storage time of one year. The green system can be widely applied to construct powerful platforms for enzyme or microorganism-driven interfacial catalysis

Clinicopathological Characteristics and Outcomes of Chinese Patients with Scanty Immune Deposits Lupus Nephritis: A Large Cohort Study from a Single Center

Objective. To assess clinicopathological characteristics of lupus nephritis patients with scanty immune deposits. Methods. The data of patients with scanty immune deposits lupus nephritis were retrospectively analyzed. Plasma ANCA and complement components were detected. Results. Among 316 cases with renal biopsy-proven lupus nephritis, 40 cases were diagnosed as scanty immune deposits. There were significantly higher value of serum creatinine (P = 0.002) and lower hemoglobin level (P = 0.009) and higher score of cellular crescents (P = 0.015) in scanty immune deposits group compared with immune complex deposits group. The frequency of positive plasma ANCA was significantly higher in scanty immune deposits group than that in immune complex deposits group (52.5% versus 10.1%, P < 0.001). As for comparisons of plasma complement components, there were significantly higher levels of C1q (P = 0.005) and Bb (P = 0.02) and lower level of factor H (P = 0.003) in scanty immune deposits group. The ratio of treatment failure was significantly higher in scanty immune deposits group than that in immune deposits group (42.5% versus 19.20%, P = 0.001). The renal outcomes were similar between the two groups. Conclusions. Patients with scanty immune deposits lupus nephritis had more severe kidney damage. ANCA and activation of complement alternative pathway might be involved in the pathogenesis of the disease.Multidisciplinary SciencesSCI(E)[email protected]

implications for health and disease

Many aspects of human physiology and behavior display rhythmicity with a period of approximately 24 h. Rhythmic changes are controlled by an endogenous time keeper, the circadian clock, and include sleep-wake cycles, physical and mental performance capability, blood pressure, and body temperature. Consequently, many diseases, such as metabolic, sleep, autoimmune and mental disorders and cancer, are connected to the circadian rhythm. The development of therapies that take circadian biology into account is thus a promising strategy to improve treatments of diverse disorders, ranging from allergic syndromes to cancer. Circadian alteration of body functions and behavior are, at the molecular level, controlled and mediated by widespread changes in gene expression that happen in anticipation of predictably changing requirements during the day. At the core of the molecular clockwork is a well-studied transcription-translation negative feedback loop. However, evidence is emerging that additional post-transcriptional, RNA-based mechanisms are required to maintain proper clock function. Here, we will discuss recent work implicating regulated mRNA stability, translation and alternative splicing in the control of the mammalian circadian clock, and its role in health and disease

Optimal design and performance analysis of a hybrid system combining a semi-submersible wind platform and point absorbers

Integrating point absorber wave energy converters (PAWECs) and an offshore floating wind platform provide a cost-effective way of joint wind and wave energy exploitation. However, the coupled dynamics of the complicated hybrid system and its influence on power performance are not well understood. Here, a frequency-domain-coupled hydrodynamics, considering the constraints and the power output through the relative motion between the PAWECs and the semi-submersible platform, is introduced to optimize the size, power take-off damping, and layout of the PAWECs. Results show that the annual wave power generation of a PAWEC can be improved by 30% using a 90° conical or a hemispherical bottom instead of a flat bottom. Additionally, while letting the PAWECs protrude out the sides of the triangular frame of the platform by a distance of 1.5 times the PAWEC radius, the total power generation can be improved by up to 18.2% without increasing the motion response of the platform. The PAWECs can reduce the resonant heave motion of the platform due to the power take-off damping force. This study provides a reference for the synergistic use of wave and wind energ