A geometric description of the set of stabilizing PID controllers

This article developed a new method to described the set of stabilizing PID control. The method is based on D-parameterization with natural description of the set. It was found that the stability crossing surface is a ruled surface that is completely determined by a curve known as discriminant. The discriminant is divided into sectors at the cusps. Corresponding to the sectors, the stability crossing surface is divided into positive and negative patches. A systematic study is conducted to identify the regions with a fixed number of right half-plane characteristic roots. The crossing directions of characteristic roots for positive patches and negative patches are also studied. As a result, a systematic method is developed to identify the regions of PID parameter such that the system is stabilized

Constant pH molecular dynamics of proteins in explicit solvent with proton tautomerism

pH is a ubiquitous regulator of biological activity, including protein‐folding, protein‐protein interactions, and enzymatic activity. Existing constant pH molecular dynamics (CPHMD) models that were developed to address questions related to the pH‐dependent properties of proteins are largely based on implicit solvent models. However, implicit solvent models are known to underestimate the desolvation energy of buried charged residues, increasing the error associated with predictions that involve internal ionizable residue that are important in processes like hydrogen transport and electron transfer. Furthermore, discrete water and ions cannot be modeled in implicit solvent, which are important in systems like membrane proteins and ion channels. We report on an explicit solvent constant pH molecular dynamics framework based on multi‐site λ‐dynamics (CPHMD MSλD ). In the CPHMD MSλD framework, we performed seamless alchemical transitions between protonation and tautomeric states using multi‐site λ‐dynamics, and designed novel biasing potentials to ensure that the physical end‐states are predominantly sampled. We show that explicit solvent CPHMD MSλD simulations model realistic pH‐dependent properties of proteins such as the Hen‐Egg White Lysozyme (HEWL), binding domain of 2‐oxoglutarate dehydrogenase (BBL) and N‐terminal domain of ribosomal protein L9 (NTL9), and the p K a predictions are in excellent agreement with experimental values, with a RMSE ranging from 0.72 to 0.84 p K a units. With the recent development of the explicit solvent CPHMD MSλD framework for nucleic acids, accurate modeling of pH‐dependent properties of both major class of biomolecules—proteins and nucleic acids is now possible. Proteins 2014; 82:1319–1331. © 2013 Wiley Periodicals, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/107513/1/prot24499-sup-0002-suppinfo02.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/107513/2/prot24499-sup-0001-suppinfo01.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/107513/3/prot24499.pd

Association of serum levels of lipid and its novel constituents with the different stages of esophageal carcinoma

<p>Abstract</p> <p>Background</p> <p>The aim of the study was to evaluate the association of immunoglobulin G type of autoantibodies to oxidized low-density lipoprotein (oxLDL-lgG) and oxLDL-lgM with the progression of esophageal squamous cell carcinoma (ESSC).</p> <p>Methods</p> <p>Residents from Feicheng, China aged 40 to 69 years were screened for esophageal lesions in a screening program conducted during the period of January 2008 to December 2006. There were 33 controls with normal esophageal squamous epithelium cells, 37 patients with basal cell hyperplasia, 47 with esophageal squamous cell dysplasia, and 43 with ESCC. All the participants were diagnosed by biopsy and histopathological examination. Adiponectin, oxidized low-density lipoprotein (oxLDL), autoantibodies against oxLDL (oxLDL-ab), OxLDL-lgG, and OxLDL-lgM were determined by enzyme linked immunosorbent assay (ELISA). Total cholesterol, High-density lipoprotein (HDL), triglyceride, serum albumin, and blood pressure were co-estimated. Analysis of covariance for lipid levels was used to control the influence of covariates.</p> <p>Results</p> <p>The level of oxLDL-lgM increased gradually along with esophageal carcinoma progression. The oxLDL-lgM levels in the ESCC group were the highest after possible covariates were controlled. Binary logistic regression showed that oxLDL-lgM had a positive correlation with the development of esophageal carcinoma, while oxLDL and oxLDL-ab had a negative correlation with ESSC. No significant association between the levels of oxLDL-lgG and adiponectin and the different stages of ESSC was observed.</p> <p>Conclusion</p> <p>The present study shows that the decreased oxLDL and oxLDL-ab and the elevated oxLDL-lgM serum levels may relate to the development and progression of ESSC.</p

Restoration of functional PAX6 in aniridia patient iPSC-derived ocular tissue models using repurposed nonsense suppression drugs

Congenital aniridia is a rare, pan-ocular disease causing severe sight loss, with only symptomatic intervention offered to patients. Approximately 40% of aniridia patients present with heterozygous nonsense variants in PAX6, resulting in haploinsufficiency. Translational readthrough inducing compounds (TRIDs) have the ability to weaken the recognition of in-frame premature stop codons (PTCs), permitting full-length protein to be translated. We have established induced pluripotent stem cell (iPSC)-derived 3D optic cups and 2D limbal epithelial stem cell (LESC) models from two aniridia patients with prevalent PAX6 nonsense mutations. Both in vitro models show reduced PAX6 protein levels, mimicking the disease. Repurposed TRIDs amlexanox and 2,6-diaminopurine (DAP), and positive control compounds ataluren and G418 were tested for their efficiency. Amlexanox was identified as the most promising TRID, increasing full-length PAX6 levels in both models, and rescuing the disease phenotype through normalization of VSX2 and cell proliferation in the optic cups and reduction of ABCG2 protein and SOX10 expression in LESC. This study highlights the significance of patient iPSC-derived cells as a new model system for aniridia and proposes amlexanox as a new putative treatment for nonsense-mediated aniridia

ΔNp63-mediated regulation of hyaluronic acid metabolism and signaling supports HNSCC tumorigenesis

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide, and several molecular pathways that underlie the molecular tumorigenesis of HNSCC have been identified. Among them, amplification or overexpression of ΔNp63 isoforms is observed in the majority of HNSCCs. Here, we unveiled a ΔNp63-dependent transcriptional program able to regulate the metabolism and the signaling of hyaluronic acid (HA), the major component of the extracellular matrix (ECM). We found that ∆Np63 is capable of sustaining the production of HA levels in cell culture and in vivo by regulating the expression of the HA synthase HAS3 and two hyaluronidase genes, HYAL-1 and HYAL-3. In addition, ∆Np63 directly regulates the expression of CD44, the major HA cell membrane receptor. By controlling this transcriptional program, ∆Np63 sustains the epithelial growth factor receptor (EGF-R) activation and the expression of ABCC1 multidrug transporter gene, thus contributing to tumor cell proliferation and chemoresistance. Importantly, p63 expression is positively correlated with CD44, HAS3, and ABCC1 expression in squamous cell carcinoma datasets and p63-HA pathway is a negative prognostic factor of HNSCC patient survival. Altogether, our data shed light on a ∆Np63-dependent pathway functionally important to the regulation of HNSCC progression

3D fusion between fluoroscopy angiograms and SPECT myocardial perfusion images to guide percutaneous coronary intervention

Background Percutaneous coronary intervention (PCI) in stable coronary artery disease (CAD) is commonly triggered by abnormal myocardial perfusion imaging (MPI). However, due to the possibilities of multivessel disease, serial stenoses and variability of coronary artery perfusion distribution, an opportunity exists to better align anatomic stenosis with perfusion abnormalities to improve revascularization decisions. This study aims to develop a multi-modality fusion approach to assist decision-making for PCI. Methods and Results Coronary arteries from fluoroscopic angiography (FA) were reconstructed into 3D artery anatomy. Left ventricular (LV) epicardial surface was extracted from SPECT. The artery anatomy and epicardial surface were non-rigidly fused. The accuracy of the 3D fusion was evaluated via both computer simulation and real patient data. Simulated FA and MPI were integrated and then compared with the ground truth from a digital phantom. The distance-based mismatch errors between simulated fluoroscopy and phantom arteries were 1.86 ± 1.43 mm for left coronary arteries (LCA) and 2.21 ± 2.50 mm for right coronary arteries (RCA). FA and SPECT images in 30 patients were integrated and then compared with the ground truth from CT angiograms. The distance-based mismatch errors between the fluoroscopy and CT arteries were 3.84 ± 3.15 mm for LCA and 5.55 ± 3.64 mm for RCA. The presence of the corresponding fluoroscopy and CT arteries in the AHA-17-segment model agreed well with a Kappa value of 0.91 (CI 0.89-0.93) for LCA and a Kappa value of 0.80 (CI 0.67-0.92) for RCA. Conclusions Our fusion approach is technically accurate to assist PCI decision-making and is clinically feasible to be used in the catheterization laboratory. Future studies are necessary to determine if fusion improves PCI-related outcomes

Effect of Rootstocks on the Volatiles in Grape Berries of Vitis vinifera L. cv. ‘Petit Verdot’

In this study, the wine grape cultivar Vitis vinifera L. cv. ‘Petit Verdot’ was used as the scion for ‘101-14’, ‘5BB’, ‘SO4’, ‘Beta’ and ‘1103P’ rootstocks as well as self-rooted control. The volatile components of ‘Petit Verdot’ grape berries from the commercial harvest period in 2016–2017 were analyzed by using head space solid phase microextraction-gas chromatography-mass spectrometry (HS-SPME-GC-MS). The results showed that the climate differences between vintages were the decisive factor affecting the contents of volatile components in ‘Petit Verdot’ grapes, which were also significantly affected by rootstocks. Compared with the self-rooted control, all five rootstocks significantly increased the contents of C6/C9 compounds in grapes. ‘5BB’ significantly increased the contents of C13-norisoprenoids and terpenes, ‘1103P’ significantly increased the content of bound carbonyl compounds, ‘101-14’ significantly increased the content of free carbonyl compounds and significantly decreased the content of bound C13-norisoprenoids, ‘Beta’ significantly increased the contents of bound C13-norisoprenoids and terpenes, and ‘SO4’ significantly increased the contents of C13-norisoprenoids, bound carbonyl compounds and free terpenes. Orthogonal partial least squares-discriminant analysis (OPLS-DA) results showed that C6/C9 compounds, such as (E)-2-hexenal, (Z)-2-hexenal and hexanal, were the common differential volatile components to differentiate the grafted grapes from the self-rooted ones. In general, grafting ‘Petit Verdot’ onto the rootstock ‘5BB’ in Beijing was conducive to the accumulation of terpenes and C13-norisoprenoids in grapes during harvest

Nonisolated switching-capacitor-integrated three- port converters with seamless PWM/PFM modulation

Efficiency and power density of power converters for interfacing photovoltaic panels, energy storage components such as batteries, and loads in photovoltaic (PV) systems become more and more important. Compared with individual converter design for different terminals, power-integrated multiport converters shows obvious advantages in simplifying the system structure, reducing the component count, and improving the operation reliability. Originated from the high power-density switched capacitor topology, a nonisolated switching-capacitor-integrated three-port converter (SCI-TPC) is presented to achieve single-stage direct power conversion among three ports. In order to minimize the cross-regulation effect, pulse-width-modulation (PWM) and pulse-frequency-modulation (PFM) are adopted to realize the flexible power regulation and achieve power balance among three ports. Main operation modes, power flow distribution, and power transfer characteristic are analyzed. With the seamless PWM and PFM hybrid modulation, the current stress can be reduced and the overall conversion efficiency over a full operating range can be improved. Main experimental results are provided to validate the effectiveness of the proposed concept