Rational Modulation Research Articles

Allosteric Coupling of Nucleotide Turnover to Bimolecular Recognition in Kinesin Motors and G Protein Switches

Kinesin motors and homologous G proteins switches coordinate a wide array of important subcellular processes, from division and growth to intracellular communication and self-organization. These functionally diverse families contain a similar core structure supporting a common mode of nucleotide dependent allostery. However, a complete atomistic scale picture of key structural dynamic mechanisms and their adaptation to control distinct functional interactions remains elusive. Here we describe results from a comparative approach that couples bioinformatics, molecular simulation and experimental protein engineering across kinesin and G protein families. This includes the prediction and experimental engineering of allosterically decoupled constitutively active heterotrimeric G proteins. Prediction and experimental verification of allosterically enhanced and mechanochemically distinct kinesin-5. Computational and experimental dissection of kinesin-microtubule interactions along with the rational modulation of kinesin processive motility - the ability of an individual motor to take multiple steps along its microtubule filament. Collectively, this work furthers our understanding of the evolutionary adaptation of a ubiquitous allosteric motif and informs mechanistic studies on many related nucleotide triphosphatases that constitute nearly 5% of human protein coding genes.Software and other material related to this work can be found at:http://thegrantlab.org/.

Supramolecular Aggregate as a High-Efficiency Gene Carrier Mediated with Optimized Assembly Structure

For cancer gene therapy, a safe and high-efficient gene carrier is a must. To resolve the contradiction between gene transfection efficiency and cytotoxicity, many polymers with complex topological structures have been synthesized, although their synthesis processes and structure control are difficult as well as the high molecular weight also bring high cytotoxicity. We proposed an alternative strategy that uses supramolecular inclusion to construct the aggregate from the small molecules for gene delivery, and to further explore the relationship between the topological assembly structure and their ability to deliver gene. Herein, PEI-1.8k-conjugating β-CD through 6-hydroxyl (PEI-6-CD) and 2-hydroxyl (PEI-2-CD) have been synthesized respectively and then assembled with diferrocene (Fc)-ended polyethylene glycol (PEG-Fc). The obtained aggregates were then used to deliver MMP-9 shRNA plasmid for MCF-7 cancer therapy. It was found that the higher gene transfection efficiency can be obtained by selecting PEI-2-CD as the host and tuning the host/guest molar ratios. With the rational modulation of supramolecular architectures, the aggregate played the functions similar to macromolecules which exhibit higher transfection efficiency than PEI-25k, but show much lower cytotoxicity because of the nature of small/low molecules. In vitro and in vivo assays confirmed that the aggregate could deliver MMP-9 shRNA plasmid effectively into MCF-7 cells and then downregulate MMP-9 expression, which induced the significant MCF-7 cell apoptosis, as well inhibit MCF-7 tumor growth with low toxicity. The supramolecular aggregates maybe become a promising carrier for cancer gene therapy and also provided an alternative strategy for designing new gene carriers.

Supplementary Schemes to Enhance the Performance of DWT-RDM-Based Blind Audio Watermarking

This paper reports two schemes aimed at enhancing the performance of an algorithm based on rational dither modulation (RDM) for the blind watermarking of audio signals. The enhanced algorithm operates in a 4th-level approximation subband, which is obtained through discrete wavelet transform (DWT) decomposition. The first scheme involves the application of a two-tap FIR lowpass filter to mask the noise induced by watermarking, while the second scheme is meant to compensate for distortion introduced by vector modulation. These two schemes make it possible for the DWT-RDM algorithm to formulate audio watermarking with a payload capacity of 689 bits per second. The embedding process is organized as parametric vector operations, which allow the implantation of binary bits into DWT coefficient vectors using two variables, respectively, corresponding to lowpass filtering and distortion compensation. Experiments aimed at evaluating the quality of the resulting audio files indicated an improvement in average ODG score from $$-0.33$$-0.33 to $$-0.26$$-0.26. Furthermore, we observed a noticeable reduction in the bit error rates when conducting robustness tests against attacks, such as brumm addition, zero crossing, noise corruption, echo addition, MPEG-1 layer 3 compression, and time shifting.

Swift Electrofluorochromism of Donor-Acceptor Conjugated Polytriphenylamines.

Electrofluorochromic (EFC) materials, which exhibit electrochemically controllable fluorescence, hold great promise in optoelectronic devices and biological analysis. Here we design such donor-acceptor (D-A) conjugated polymers-P(TPACO) and P(TCEC)-that contain the same electron-rich and oxidizable polytriphenylamine (PTPA) as π-backbone, yet with different electron-deficient ketone and cyano units as pendant groups, respectively. They both exhibit solvatochromic effects due to intrinsic characteristics of intramolecular charge transfer (ICT). Compared to P(TPACO), P(TCEC) shows stronger ICT, which leads to higher electrochemical oxidation potential and lower ion diffusion coefficient. Moreover, both polymers present simultaneous electrochromic (EC) and EFC behaviors with multistate display and remarkably rapid fluorescence response. The response time of P(TPACO) is as short as 0.19 s, nearly 4-fold faster than that of P(TCEC) (0.92 s). Such rapid response is found to be determined by the ion diffusion coefficient which is associated with the ICT nature. Finally, the EFC display device based on P(TPACO) is successfully demonstrated, which shows green fluorescence ON/OFF switching upon applied potentials. This work has successfully demonstrated that swift EFCs can be achieved by rational modulation of the ICT effect in such D-A conjugated polymers.

On the Optimization of a PSP-Based CPM Detection

This paper deals with a reduced-complexity per survivor processing-based CPM demodulation. It relies on a trellis with reduced state number and defined from a rational modulation index possibly different from the transmit modulation index and referred to as virtual receiver modulation index. The virtual receiver modulation index should be chosen so as to achieve a tradeoff between error-rate performance and complexity reduction. The main purpose of this paper is the choice of the virtual receiver modulation index. It gives guidelines to discard the values of the virtual receiver modulation index, that degrade the error-rate performance. Two criteria are used. The first one considers the uncoded CPM case and is based on an approximation of the minimal Euclidean distance. The second one is related to the bit interleaved coded CPM case and resorts to an EXIT chart to analyze the convergence of the iterative receiver.

Initiation of Chondrocyte Self-Assembly Requires an Intact Cytoskeletal Network.

Self-assembly and self-organization have recently emerged as robust scaffold-free tissue engineering methodologies that can be used to generate various tissues, including cartilage, vessel, and liver. Self-assembly, in particular, is a scaffold-free platform for tissue engineering that does not require the input of exogenous energy to the system. Although self-assembly can generate functional tissues, most notably neocartilage, the mechanisms of self-assembly remain unclear. To study the self-assembling process, we used articular chondrocytes as a model to identify parameters that can affect this process. Specifically, the roles of cell-cell and cell-matrix adhesion molecules, surface-bound collagen, and the actin cytoskeletal network were investigated. Using time-lapse imaging, we analyzed the early stages of chondrocyte self-assembly. Within hours, chondrocytes rapidly coalesced into cell clusters before compacting to form tight cellular structures. Chondrocyte self-assembly was found to depend primarily on integrin function and secondarily on cadherin function. In addition, actin or myosin II inhibitors prevented chondrocyte self-assembly, suggesting that cell adhesion alone is not sufficient, but rather the active contractile actin cytoskeleton is essential for proper chondrocyte self-assembly and the formation of neocartilage. Better understanding of the self-assembly mechanisms allows for the rational modulation of this process toward generating neocartilages with improved properties. These findings are germane to understanding self-assembly, an emerging platform for tissue engineering of a plethora of tissues, especially as these neotissues are poised for translation.

Microporous Metal–Organic Framework Stabilized by Balanced Multiple Host–Couteranion Hydrogen-Bonding Interactions for High-Density CO2 Capture at Ambient Conditions

Microporous metal organic frameworks (MOFs) show promising application in several fields, but they often suffer from the weak robustness and stability after the removal of guest molecules. Here, three isostructural cationic metal-organic frameworks {[(Cu4Cl)(cpt)4(H2O)4]·3X·4DMAc·CH3OH·5H2O} (FJU-14, X = NO3, ClO4, BF4; DMAc = N,N'-dimethylacetamide) containing two types of polyhedral nanocages, one octahedron, and another tetrahedron have been synthesized from bifunctional organic ligands 4-(4H-1,2,4-triazol-4-yl) benzoic acid (Hcpt) and various copper salts. The series of MOFs FJU-14 are demonstrated as the first examples of the isostructural MOFs whose robustness, thermal stability, and CO2 capacity can be greatly improved via rational modulation of counteranions in the tetrahedral cages. The activated FJU-14-BF4-a containing BF4(-) anion can take CO2 of 95.8 cm(3) cm(-3) at ambient conditions with an adsorption enthalpy only of 18.8 kJ mol(-1). The trapped CO2 density of 0.955 g cm(-3) is the highest value among the reported MOFs. Dynamic fixed bed breakthrough experiments indicate that the separation of CO2/N2 mixture gases through a column packed with FJU-14-BF4-a solid can be efficiently achieved. The improved robustness and thermal stability for FJU-14-BF4-a can be attributed to the balanced multiple hydrogen-bonding interactions (MHBIs) between the BF4(-) counteranion and the cationic skeleton, while the high-density and low-enthalpy CO2 capture on FJU-14-BF4-a can be assigned to the multiple-point interactions between the adsorbate molecules and the framework as well as with its counteranions, as proved by single-crystal structures of the guest-free and CO2-loaded FJU-14-BF4-a samples.

PRX1 knockdown potentiates vitamin K3 toxicity in cancer cells: a potential new therapeutic perspective for an old drug.

BackgroundMany promising anticancer molecules are abandoned during the course from bench to bedside due to lack of clear-cut efficiency and/or severe side effects. Vitamin K3 (vitK3) is a synthetic naphthoquinone exhibiting significant in vitro and in vivo anticancer activity against multiple human cancers, and has therapeutic potential when combined with other anticancer molecules. The major mechanism for the anticancer activity of vitK3 is the generation of cytotoxic reactive oxygen species (ROS). We thus reasoned that a rational redox modulation of cancer cells could enhance vitK3 anticancer efficiency.MethodsCancer cell lines with peroxiredoxin 1 (PRX1) gene transiently or stably knocked-down and corresponding controls were exposed to vitK3 as well as a set of anticancer molecules, including vinblastine, taxol, doxorubicin, daunorubicin, actinomycin D and 5-fluorouracil. Cytotoxic effects and cell death events were evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT)-based assay, cell clonogenic assay, measurement of mitochondrial membrane potential and annexin V/propidium iodide double staining. Global ROS accumulation and compartment-specific H2O2 generation were determined respectively by a redox-sensitive chemical probe and H2O2-sensitive sensor HyPer. Oxidation of endogenous antioxidant proteins including TRX1, TRX2 and PRX3 was monitored by redox western blot.ResultsWe observed that the PRX1 knockdown in HeLa and A549 cells conferred enhanced sensitivity to vitK3, reducing substantially the necessary doses to kill cancer cells. The same conditions (combination of vitK3 and PRX1 knockdown) caused little cytotoxicity in non-cancerous cells, suggesting a cancer-cell-selective property. Increased ROS accumulation had a crucial role in vitK3-induced cell death in PRX1 knockdown cells. The use of H2O2-specific sensors HyPer revealed that vitK3 lead to immediate accumulation of H2O2 in the cytosol, nucleus, and mitochondrial matrix. PRX1 silencing significantly up-regulated mRNA and protein levels of NRH:quinone oxidoreductase 2, which was partially responsible for vitK3-induced ROS accumulation and consequent cell death.ConclusionOur data suggest that PRX1 inactivation could represent an interesting strategy to enhance cancer cell sensitivity to vitK3, providing a potential new therapeutic perspective for this old molecule. Conceptually, a combination of drugs that modulate intracellular redox states and drugs that operate through the generation of ROS could be a new therapeutic strategy for cancer treatment.

Introduction of a Framework for Dynamic Knowledge Representation of the Control Structure of Transplant Immunology: Employing the Power of Abstraction with a Solid Organ Transplant Agent-Based Model.

Agent-based modeling has been used to characterize the nested control loops and non-linear dynamics associated with inflammatory and immune responses, particularly as a means of visualizing putative mechanistic hypotheses. This process is termed dynamic knowledge representation and serves a critical role in facilitating the ability to test and potentially falsify hypotheses in the current data- and hypothesis-rich biomedical research environment. Importantly, dynamic computational modeling aids in identifying useful abstractions, a fundamental scientific principle that pervades the physical sciences. Recognizing the critical scientific role of abstraction provides an intellectual and methodological counterweight to the tendency in biology to emphasize comprehensive description as the primary manifestation of biological knowledge. Transplant immunology represents yet another example of the challenge of identifying sufficient understanding of the inflammatory/immune response in order to develop and refine clinically effective interventions. Advances in immunosuppressive therapies have greatly improved solid organ transplant (SOT) outcomes, most notably by reducing and treating acute rejection. The end goal of these transplant immune strategies is to facilitate effective control of the balance between regulatory T cells and the effector/cytotoxic T-cell populations in order to generate, and ideally maintain, a tolerant phenotype. Characterizing the dynamics of immune cell populations and the interactive feedback loops that lead to graft rejection or tolerance is extremely challenging, but is necessary if rational modulation to induce transplant tolerance is to be accomplished. Herein is presented the solid organ agent-based model (SOTABM) as an initial example of an agent-based model (ABM) that abstractly reproduces the cellular and molecular components of the immune response to SOT. Despite its abstract nature, the SOTABM is able to qualitatively reproduce acute rejection and the suppression of acute rejection by immunosuppression to generate transplant tolerance. The SOTABM is intended as an initial example of how ABMs can be used to dynamically represent mechanistic knowledge concerning transplant immunology in a scalable and expandable form and can thus potentially serve as useful adjuncts to the investigation and development of control strategies to induce transplant tolerance.

Model-driven intracellular redox status modulation for increasing isobutanol production in Escherichia coli.

BackgroundFew strains have been found to produce isobutanol naturally. For building a high performance isobutanol-producing strain, rebalancing redox status of the cell was very crucial through systematic investigation of redox cofactors metabolism. Then, the metabolic model provided a powerful tool for the rational modulation of the redox status.ResultsFirstly, a starting isobutanol-producing E. coli strain LA02 was engineered with only 2.7 g/L isobutanol produced. Then, the genome-scale metabolic modeling was specially carried out for the redox cofactor metabolism of the strain LA02 by combining flux balance analysis and minimization of metabolic adjustment, and the GAPD reaction catalyzed by the glyceraldehyde-3-phosphate dehydrogenase was predicted as the key target for redox status improvement. Under guidance of the metabolic model prediction, a gapN-encoding NADP+ dependent glyceraldehyde-3-phosphate dehydrogenase pathway was constructed and then fine-tuned using five constitutive promoters. The best strain LA09 was obtained with the strongest promoter BBa_J23100. The NADPH/NADP + ratios of strain LA09 reached 0.67 at exponential phase and 0.64 at stationary phase. The redox modulations resulted in the decrease production of ethanol and lactate by 17.5 and 51.7% to 1.32 and 6.08 g/L, respectively. Therefore, the isobutanol titer was increased by 221% to 8.68 g/L.ConclusionsThis research has achieved rational redox status improvement of isobutanol-producing strain under guidance of the prediction and modeling of the genome-scale metabolic model of isobutanol-producing E. coli strain with the aid of synthetic promoters. Therefore, the production of isobutanol was dramatically increased by 2.21-fold from 2.7 to 8.68 g/L. Moreover, the developed model-driven method special for redox cofactor metabolism was of very helpful to the redox status modulation of other bio-products.Electronic supplementary materialThe online version of this article (doi:10.1186/s13068-015-0291-2) contains supplementary material, which is available to authorized users.

Rational Modulation of the Induced-Fit Conformational Change for Slow-Onset Inhibition in Mycobacterium tuberculosis InhA.

Slow-onset enzyme inhibitors are the subject of considerable interest as an approach to increasing the potency of pharmaceutical compounds by extending the residence time of the inhibitor on the target (the lifetime of the drug-receptor complex). However, rational modulation of residence time presents significant challenges because it requires additional mechanistic insight, such as the nature of the transition state for postbinding isomerization. Our previous work, based on X-ray crystallography, enzyme kinetics, and molecular dynamics simulation, suggested that the slow step in inhibition of the Mycobacterium tuberculosis enoyl-ACP reductase InhA involves a change in the conformation of the substrate binding loop from an open state in the initial enzyme-inhibitor complex to a closed state in the final enzyme-inhibitor complex. Here, we use multidimensional free energy landscapes for loop isomerization to obtain a computational model for the transition state. The results suggest that slow-onset inhibitors crowd key side chains on helices that slide past each other during isomerization, resulting in a steric clash. The landscapes become significantly flatter when residues involved in the steric clash are replaced with alanine. Importantly, this lower barrier can be increased by rational inhibitor redesign to restore the steric clash. Crystallographic studies and enzyme kinetics confirm the predicted effects on loop structure and flexibility, as well as inhibitor residence time. These loss and regain of function studies validate our mechanistic hypothesis for interactions controlling substrate binding loop isomerization, providing a platform for the future design of inhibitors with longer residence times and better in vivo potency. Similar opportunities for slow-onset inhibition via the same mechanism are identified in other pathogens.

A DWT-Based Rational Dither Modulation Scheme for Effective Blind Audio Watermarking

A scheme jointly exploring the rational dither modulation (RDM) and auditory masking properties in the discrete wavelet transform (DWT) domain is proposed to achieve effective blind audio watermarking. The embedding of binary information is carried out by modulating coefficient vectors in the 5th-level approximation subband using the quantization steps estimated from past watermarked vectors. The robustness and payload capacity of the proposed scheme are maneuverable by varying vector dimensions, while the imperceptibility is ensured by constraining quantization noise below the auditory masking threshold. Furthermore, the periodic characteristic inherited in the RDM formulation can be used to re-establish synchronization for accurate watermark extraction. Experimental results show that the proposed DWT---RDM approach renders a near-zero objective difference grade in the perceptual evaluation of audio quality even when the signal-to-noise ratio maintains at a level near 20 dB. In most digital signal processing attacks, the bit error rates of retrieved watermarks are sufficiently low as compared to other recently developed methods with fewer payload capacities.

Rational modulation of the innate immune system for neuroprotection in ischemic stroke.

The innate immune system plays a dualistic role in the evolution of ischemic brain damage and has also been implicated in ischemic tolerance produced by different conditioning stimuli. Early after ischemia, perivascular astrocytes release cytokines and activate metalloproteases (MMPs) that contribute to blood–brain barrier (BBB) disruption and vasogenic oedema; whereas at later stages, they provide extracellular glutamate uptake, BBB regeneration and neurotrophic factors release. Similarly, early activation of microglia contributes to ischemic brain injury via the production of inflammatory cytokines, including tumor necrosis factor (TNF) and interleukin (IL)-1, reactive oxygen and nitrogen species and proteases. Nevertheless, microglia also contributes to the resolution of inflammation, by releasing IL-10 and tumor growth factor (TGF)-β, and to the late reparative processes by phagocytic activity and growth factors production. Indeed, after ischemia, microglia/macrophages differentiate toward several phenotypes: the M1 pro-inflammatory phenotype is classically activated via toll-like receptors or interferon-γ, whereas M2 phenotypes are alternatively activated by regulatory mediators, such as ILs 4, 10, 13, or TGF-β. Thus, immune cells exert a dualistic role on the evolution of ischemic brain damage, since the classic phenotypes promote injury, whereas alternatively activated M2 macrophages or N2 neutrophils prompt tissue remodeling and repair. Moreover, a subdued activation of the immune system has been involved in ischemic tolerance, since different preconditioning stimuli act via modulation of inflammatory mediators, including toll-like receptors and cytokine signaling pathways. This further underscores that the immuno-modulatory approach for the treatment of ischemic stroke should be aimed at blocking the detrimental effects, while promoting the beneficial responses of the immune reaction.

Flow through Fluorescence Detection of Phosphate in Human Saliva Based on Sensitized Turn-On Photoluminescence of CdS Quantum Dots

ABSTRACTThe development of fluorescent turn-on probes for the determination of inorganic anions based on fluorescent semiconductor nanocrystals (quantum dots) has recently attracted great attention. Methods reported so far enable anion sensing at elevated concentration levels and usually with low selectivity against other abundant matrix components. In this work, we describe an alternative approach that combines the appropriate modulation of nanocrystal surface chemistry (i.e., stabilization) with rational design and modulation of the experimental conditions (i.e., flow injection analysis) in order to deliver an expedient flow through method that enables the determination of phosphate at low concentration levels and with good selectivity. The developed method was successfully applied to the determination of phosphate in artificial and human saliva with good analytical features in terms of reproducibility and repeatability (2.3–9.2%), recoveries from fortified samples (96.0–112.0%), linearity of response curves to phosphate concentrations (R2 > 0.99), and satisfactory sensitivity (<1 µM), providing a significant improvement to previous fluorescent turn-on quantum dot probes.

Molecular recognition of PTS-1 cargo proteins by Pex5p: implications for protein mistargeting in primary hyperoxaluria.

Peroxisomal biogenesis and function critically depends on the import of cytosolic proteins carrying a PTS1 sequence into this organelle upon interaction with the peroxin Pex5p. Recent structural studies have provided important insights into the molecular recognition of cargo proteins by Pex5p. Peroxisomal import is a key feature in the pathogenesis of primary hyperoxaluria type 1 (PH1), where alanine:glyoxylate aminotransferase (AGT) undergoes mitochondrial mistargeting in about a third of patients. Here, we study the molecular recognition of PTS1 cargo proteins by Pex5p using oligopeptides and AGT variants bearing different natural PTS1 sequences, and employing an array of biophysical, computational and cell biology techniques. Changes in affinity for Pex5p (spanning over 3–4 orders of magnitude) reflect different thermodynamic signatures, but overall bury similar amounts of molecular surface. Structure/energetic analyses provide information on the contribution of ancillary regions and the conformational changes induced in Pex5p and the PTS1 cargo upon complex formation. Pex5p stability in vitro is enhanced upon cargo binding according to their binding affinities. Moreover, we provide evidence that the rational modulation of the AGT: Pex5p binding affinity might be useful tools to investigate mistargeting and misfolding in PH1 by pulling the folding equilibria towards the native and peroxisomal import competent state.

Solvent induced rapid modulation of micro/nano structures of metal carboxylates coordination polymers: mechanism and morphology dependent magnetism.

Rational modulation of morphology is very important for functional coordination polymers (CPs) micro/nanostructures, and new strategies are still desired to achieve this challenging target. Herein, organic solvents have been established as the capping agents for rapid modulating the growth of metal-carboxylates CPs in organic solvent/water mixtures at ambient conditions. Co-3,5-pyridinedicarboxylate (pydc) CPs was studied here as the example. During the reaction, the organic solvents exhibited three types of modulation effect: anisotropic growth, anisotropic growth/formation of new crystalline phase and the formation of new crystalline phase solely, which was due to the variation of their binding ability with metal cations. The following study revealed that the binding ability was critically affected by their functional groups and molecular size. Moreover, their modulation effect could be finely tuned by changing volume ratios of solvent mixtures. Furthermore, they could be applied for modulating other metal-carboxylates CPs: Co-1,3,5-benzenetricarboxylic (BTC), Zn-pydc and Eu-pydc etc. Additionally, the as-prepared Co-pydc CPs showed a fascinating morphology-dependent antiferromagnetic behavior.

Rational targeting of subclasses of intermolecular interactions: elimination of nonspecific binding for analyte sensing.

The ability to target and control intermolecular interactions is crucial in the development of several different technologies. Here we offer a tool to rationally design liquid media systems that can modulate specific intermolecular interactions. This has broad implications in deciphering the nature of intermolecular forces in complex solutions and offers insight into the forces that govern both specific and nonspecific binding in a given system. Nonspecific binding still continues to be a problem when dealing with analyte detection across a range of different detection technologies. Here, we exemplify the problem of nonspecific binding on model membrane systems and when dealing with low-abundance protein detection on commercially available SPR technology. A range of different soluble reagents that target specific subclasses of intermolecular interactions have been tested and optimized to virtually eliminate nonspecific binding while leaving specific interactions unperturbed. Thiocyanate ions are used to target nonpolar interactions, and small reagents such as glycylglycylglycine are used to modulate the dielectric constant, which targets charge-charge and dipole interactions. We show that with rational design and careful modulation these reagents offer a step forward in dissecting the intermolecular forces that govern binding, alongside offering nonspecific binding elimination in detection systems.

Towards Rational Modulation of In‐Plane Molecular Arrangements in Metal–Organic Framework Nanosheets

AbstractA strategy to modulate the in‐plane structural arrangement in preferentially oriented crystalline metal–organic framework (MOF) nanosheets assembled by a two‐dimensional interfacial reaction between porphyrin units and metal ion linkers is reported. Starting with a tetratopic porphyrin MOF nanofilm, NAFS‐2, the framework size and shape are modified by employing specially designed building units, a trans‐ditopic and an expanded tetratopic porphyrin, and Cu2+ linkers. Reducing the number of binding parts affords a MOF nanosheet, NAFS‐31, with a distorted in‐plane structure. Extension of the peripheral substituents, while maintaining the tetratopic porphyrin geometry, results in marked unit cell size enlargement in an undistorted square grid in the MOF nanofilm, NAFS‐41. The exquisite geometric control that these structural modifications entail is valuable to allow switching of chemical/physical properties of the nanosheets and lead to realization of their use in nanotechnological applications.

Egyptian concept of rational immune modulation: nature-friendly lifestyle for taking athero-protective phenotype.

A slightly lower rate of atherosclerosis in some tropical regions such as the Nile delta in Egypt, Saudi Arabia, Yemen and sub-Sahara Africa is associated with evidences of increased helminthic co-infection. Attempts to eradicate helminthic infections led to the shift of immune balance toward T helper 1 cells and their related cytokines. This shift is parallel with atherogenesis and its related complications. Atherosclerosis is a degenerative man-made disease which begins in early life. Thus, preventive strategies should begin at the same time. As an example to follow, living with old friends, adaption of a more nature-friendly lifestyle and "fine immune-modulation" plans from early childhood, like Egyptians, seems a good option. Finally, a proper intentional balance between T helper 1 and 2 cells should be defended and constructed environmentally in the manner compatible with modern hygiene using a soft application of old hygiene. This needs robust understanding of atheroprotective habits in regions with lower burden of atherosclerosis.

Multiband effects on Fulde-Ferrell-Larkin-Ovchinnikov states of Pauli-limited superconductors

Multiband effects on Fulde-Ferrell-Larkin-Ovchinnikov (FFLO) states of a Pauli-limiting two-band superconductor are studied theoretically in the wide range of parameters, based on the Bogoliubov-de Gennes equation. First, we examine the phase diagrams of two-band systems with a passive band in which the intraband pairing interaction is absent and superconductivity is induced by a Cooper pair tunneling from an active band. The critical field of Bardeen-Cooper-Schrieffer to FFLO states becomes lower than the Lifshitz point with increasing the interband tunneling strength. We also study the thermodynamics of Pauli-limiting two-band superconductors with nonzero intraband pairing interactions. As a consequence of a competing effect between two bands, the FFLO phase is divided into two phases: ${Q}_{1}$- and ${Q}_{2}$-FFLO phases. In a particular case, the latter is further subdivided into a family of FFLO states with rational modulation lengths, where the spatial structure of the pair potential is approximately describable with sinusoidal functions with multiple modulation wave numbers. The resultant phase diagram is qualitatively different from that in a single-band superconductor and gives rise to a devil's staircase structure in the field dependence of physical quantities.