Adsorption behaviour of molecularly imprinted-beta-cyclodextrin polymers prepared by reversible addition-fragmentation chain transfer (RAFT) polymerization for selective recognition of benzylparaben

Molecularly imprinted polymers (MIPs) are kinds of powerful materials with promising selective molecule recognition abilities. However, the conventional MIPs have relatively low binding capacity. In order to improve this characteristic of MIPs, the modification monomer based on β-cyclodextrin (β-CD) and the essential of reversible addition�fragmentation chain transfer (RAFT) polymerization process were studied to generate potential MIPs. The study focuses on the characterization and adsorption behaviour of MIPs for selective recognition of benzylparaben (BzP) analyte. The potential of β-CD in MIP was investigated by synthesizing a reversible addition-fragmentation chain transfer molecularly imprinted methacrylic acid functionalized β-cyclodextrin polymer; RAFT�MIP(MAA-β-CD) based on methacrylic acid functionalized β-cyclodextrin (MAA-β-CD) monomer, which was then compared to a reversible addition-fragmentation chain transfer molecularly imprinted methacrylic acid polymer; RAFT-MIP(MAA) synthesized without β-CD. Both MIPs were prepared by the RAFT polymerization process in bulk polymerization method. The resulting MIPs were characterized using Fourier Transform Infrared Spectroscopy (FTIR), Field Scanning Electron Microscope (FESEM) and Brunauer-Emmett-Teller (BET) analysis. The batch adsorption study that includes studying of the pH, kinetic, isotherm and thermodynamic was conducted. The essential of RAFT polymerization on MIP was studied by comparing RAFT-MIP(MAA-β-CD) with the molecularly imprinted methacrylic acid functionalized β-cyclodextrin polymer; MIP(MAA-β-CD) was synthesized without RAFT agent, and characterized by using FTIR, elemental analysis, FESEM and BET. The binding experiments demonstrated that the RAFT-MIP(MAA-β-CD) has a higher binding capacity and higher accessibility compared to RAFT-MIP(MAA) and MIP(MAA-β-CD) for selective of BzP, respectively. The β-CD and RAFT polymerization process improved the MIP’s physical properties and iv enhanced its recognition capacity, thus affecting the adsorption behaviour of RAFT�MIP(MAA-β-CD). The effects of RAFT polymerization process were also investigated by a reversible addition-fragmentation transfer molecularly imprinted hydroxylethyl methacrylate functionalized β-cyclodextrin polymer; RAFT-MIP(HEMA-β-CD). The RAFT-MIP(HEMA-β-CD) was synthesized based on the hydroxylethyl-methacrylate functionalized β-cyclodextrin (HEMA-β-CD) monomer and was prepared by the RAFT polymerization process in bulk polymerization method. The molecularly imprinted hydroxylethyl-methacrylate functionalized β-cyclodextrin polymer; MIP(HEMA-β-CD) without a RAFT agent was synthesized as comparison. A similar study to RAFT�MIP(MAA-β-CD) had also been carried out for RAFT-MIP(HEMA-β-CD).The effects of RAFT polymerization on RAFT-MIP(HEMA-β-CD) were contrasted with RAFT�MIP(MAA-β-CD). The compact and non-porous morphology of RAFT-MIP(HEMA-β�CD) reduces its binding capacity performance compared to MIP(HEMA-β-CD). Thus, this directly affected the RAFT-MIP(HEMA-β-CD) adsorption behaviour towards BzP. It was resulted that the RAFT polymerization had not improved the synthesis of RAFT�MIP(HEMA-β-CD). Careful choice of RAFT agent and monomer is essential in realizing good control over the RAFT-MIP polymerization process, and generating potential MIP

Evaluation of melanin-targeted radiotherapy in combination with radiosensitizing drugs for the treatment of melanoma

The incidence of malignant melanoma is rising faster than that of any other cancer in the United States. An [131I]-labeled benzamide - [131I]MIP-1145 - selectively targets melanin, reduces melanoma tumor burden and increases survival in preclinical models. Our purpose was to determine the potential of radiosensitizers to enhance the anti-tumor efficacy of [131I]MIP-1145. Melanotic (A2058) and amelanotic (A375 and SK-N-BE(2c)) cells were treated with [131I]MIP-1145 as a single agent or in combination with drugs with radiosenitizing potential. Cellular uptake of [131I]MIP-1145 and toxicity were assessed in monolayer culture. The interaction between radiosensitizers and [131I]MIP-1145 was evaluated by combination index analysis in monolayer cultures and by delayed growth of multicellular tumor spheroids. [131I]MIP-1145 was taken up by and was toxic to melanotic cells but not amelanotic cells. Combination treatments comprising [131I]MIP-1145 with the topoisomerase inhibitor topotecan or the PARP-1 inhibitor AG014699 resulted in synergistic clonogenic cell kill and enhanced delay of the growth of spheroids derived from melanotic melanoma cells. The proteasome inhibitor bortezomib had no synergistic cytotoxic effect with [131I]MIP-1145 and failed to enhance the delay of spheroid growth. Following combination treatment of amelanotic cells, neither synergistic clonogenic cell kill nor enhanced growth delay of spheroids was observed

The structural organization and protein composition of lens fiber junctions.

The structural organization and protein composition of lens fiber junctions isolated from adult bovine and calf lenses were studied using combined electron microscopy, immunolocalization with monoclonal and polyclonal anti-MIP and anti-MP70 (two putative gap junction-forming proteins), and freeze-fracture and label-fracture methods. The major intrinsic protein of lens plasma membranes (MIP) was localized in single membranes and in an extensive network of junctions having flat and undulating surface topologies. In wavy junctions, polyclonal and monoclonal anti-MIPs labeled only the cytoplasmic surface of the convex membrane of the junction. Label-fracture experiments demonstrated that the convex membrane contained MIP arranged in tetragonal arrays 6-7 nm in unit cell dimension. The apposing concave membrane of the junction displayed fracture faces without intramembrane particles or pits. Therefore, wavy junctions are asymmetric structures composed of MIP crystals abutted against particle-free membranes. In thin junctions, anti-MIP labeled the cytoplasmic surfaces of both apposing membranes with varying degrees of asymmetry. In thin junctions, MIP was found organized in both small clusters and single membranes. These small clusters also abut against particle-free apposing membranes, probably in a staggered or checkerboard pattern. Thus, the structure of thin and wavy junctions differed only in the extent of crystallization of MIP, a property that can explain why this protein can produce two different antibody-labeling patterns. A conclusion of this study is that wavy and thin junctions do not contain coaxially aligned channels, and, in these junctions, MIP is unlikely to form gap junction-like channels. We suggest MIP may behave as an intercellular adhesion protein which can also act as a volume-regulating channel to collapse the lens extracellular space. Junctions constructed of MP70 have a wider overall thickness (18-20 nm) and are abundant in the cortical regions of the lens. A monoclonal antibody raised against this protein labeled these thicker junctions on the cytoplasmic surfaces of both apposing membranes. Thick junctions also contained isolated clusters of MIP inside the plaques of MP70. The role of thick junctions in lens physiology remains to be determined

Increased risk for T cell autoreactivity to ß-cell antigens in the mice expressing the Avy obesity-associated gene.

There has been considerable debate as to whether obesity can act as an accelerator of type 1 diabetes (T1D). We assessed this possibility using transgenic mice (MIP-TF mice) whose ß-cells express enhanced green fluorescent protein (EGFP). Infecting these mice with EGFP-expressing murine herpes virus-68 (MHV68-EGFP) caused occasional transient elevation in their blood glucose, peri-insulitis, and Th1 responses to EGFP which did not spread to other ß-cell antigens. We hypothesized that obesity-related systemic inflammation and ß-cell stress could exacerbate the MHV68-EGFP-induced ß-cell autoreactivity. We crossed MIP-TF mice with Avy mice which develop obesity and provide models of metabolic disease alongside early stage T2D. Unlike their MIP-TF littermates, MHV68-EGFP-infected Avy/MIP-TF mice developed moderate intra-insulitis and transient hyperglycemia. MHV68-EGFP infection induced a more pronounced intra-insulitis in older, more obese, Avy/MIP-TF mice. Moreover, in MHV68-EGFP-infected Avy/MIP-TF mice, Th1 reactivity spread from EGFP to other ß-cell antigens. Thus, the spreading of autoreactivity among ß-cell antigens corresponded with the transition from peri-insulitis to intra-insulitis and occurred in obese Avy/MIP-TF mice but not lean MIP-TF mice. These observations are consistent with the notion that obesity-associated systemic inflammation and ß-cell stress lowers the threshold necessary for T cell autoreactivity to spread from EGFP to other ß-cell autoantigens

Perfect zero knowledge for quantum multiprover interactive proofs

In this work we consider the interplay between multiprover interactive proofs, quantum entanglement, and zero knowledge proofs - notions that are central pillars of complexity theory, quantum information and cryptography. In particular, we study the relationship between the complexity class MIP$^*$, the set of languages decidable by multiprover interactive proofs with quantumly entangled provers, and the class PZKMIP$^*$, which is the set of languages decidable by MIP$^*$ protocols that furthermore possess the perfect zero knowledge property. Our main result is that the two classes are equal, i.e., MIP$^* =$ PZKMIP$^*$. This result provides a quantum analogue of the celebrated result of Ben-Or, Goldwasser, Kilian, and Wigderson (STOC 1988) who show that MIP $=$ PZKMIP (in other words, all classical multiprover interactive protocols can be made zero knowledge). We prove our result by showing that every MIP$^*$ protocol can be efficiently transformed into an equivalent zero knowledge MIP$^*$ protocol in a manner that preserves the completeness-soundness gap. Combining our transformation with previous results by Slofstra (Forum of Mathematics, Pi 2019) and Fitzsimons, Ji, Vidick and Yuen (STOC 2019), we obtain the corollary that all co-recursively enumerable languages (which include undecidable problems as well as all decidable problems) have zero knowledge MIP$^*$ protocols with vanishing promise gap

Automatic Pulmonary Nodule Detection in CT Scans Using Convolutional Neural Networks Based on Maximum Intensity Projection

Accurate pulmonary nodule detection is a crucial step in lung cancer screening. Computer-aided detection (CAD) systems are not routinely used by radiologists for pulmonary nodule detection in clinical practice despite their potential benefits. Maximum intensity projection (MIP) images improve the detection of pulmonary nodules in radiological evaluation with computed tomography (CT) scans. Inspired by the clinical methodology of radiologists, we aim to explore the feasibility of applying MIP images to improve the effectiveness of automatic lung nodule detection using convolutional neural networks (CNNs). We propose a CNN-based approach that takes MIP images of different slab thicknesses (5 mm, 10 mm, 15 mm) and 1 mm axial section slices as input. Such an approach augments the two-dimensional (2-D) CT slice images with more representative spatial information that helps discriminate nodules from vessels through their morphologies. Our proposed method achieves sensitivity of 92.67% with 1 false positive per scan and sensitivity of 94.19% with 2 false positives per scan for lung nodule detection on 888 scans in the LIDC-IDRI dataset. The use of thick MIP images helps the detection of small pulmonary nodules (3 mm-10 mm) and results in fewer false positives. Experimental results show that utilizing MIP images can increase the sensitivity and lower the number of false positives, which demonstrates the effectiveness and significance of the proposed MIP-based CNNs framework for automatic pulmonary nodule detection in CT scans. The proposed method also shows the potential that CNNs could gain benefits for nodule detection by combining the clinical procedure.Comment: Submitted to IEEE TM

Fast Non-Parametric Learning to Accelerate Mixed-Integer Programming for Online Hybrid Model Predictive Control

Today's fast linear algebra and numerical optimization tools have pushed the frontier of model predictive control (MPC) forward, to the efficient control of highly nonlinear and hybrid systems. The field of hybrid MPC has demonstrated that exact optimal control law can be computed, e.g., by mixed-integer programming (MIP) under piecewise-affine (PWA) system models. Despite the elegant theory, online solving hybrid MPC is still out of reach for many applications. We aim to speed up MIP by combining geometric insights from hybrid MPC, a simple-yet-effective learning algorithm, and MIP warm start techniques. Following a line of work in approximate explicit MPC, the proposed learning-control algorithm, LNMS, gains computational advantage over MIP at little cost and is straightforward for practitioners to implement