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The tacticity effects on the water-vapor sorption of the thin films of poly(N-ethylacrylamide) (PNEAm) and poly(N,N-diethylacrylamide) (PNdEAm) are investigated by the quartz crystal microbalance method and infrared spectroscopy. The quantity of sorbed water on the spin-coated films of isotactic-rich PNEAm is larger than that of atactic one. For PNdEAm, the syndiotactic-rich polymer film absorbs more water. The amide I or C=O stretching band of the polymers are monitored during water sorption on the spin-coated films. The result indicates that the water-sorption site is also influenced by the tacticity of the polymers. The annealing of these films wipes out the tacticity dependence of water sorption, indicating that the water-sorption sites in the spin-coated films are voids around C=O groups that are made by evaporation of solvent during spin-coating (so-called, the “solvent-imprint” effect). The isotactic-rich PNEAm is more influenced by the solvent-imprint effect than the syndiotactic-rich one, while an opposite tendency is found for PNdEAm.

Background: Over 30% of the population of Okinawa Prefecture have a high body mass index. The incidence of hypertension and dyslipidaemia has also increased in recent years. We found that Ooitabi (Ficus pumila L.), a plant native to Okinawa, was useful for hypertension. During ancient times, the extracts of Ooitabi leaves were used for making Ishimaki tea in some areas of Okinawa Prefecture. The plants in Okinawa are rich in antioxidants, and four flavonoid glycosides, including rutin, have been identified in Ooitabi. Methods: In the present study, we conducted clinical verification tests on the effects of drinking Ishimaki tea on outpatients with hypertension and dyslipidaemia. Of 3814 Japanese patients who underwent medical check‐ups in Okinawa, 38 individuals with high blood pressure, dyslipidaemia, liver dysfunction and gout visited our hospital as outpatients and were asked to drink Ishimaki tea. Results: After 3 months, there were significant reductions in body mass index, systolic and diastolic blood pressure, total cholesterol, low‐density lipoprotein cholesterol, γ‐glutamyltrans peptidase, uric acid and ratio of blood vessel insulin resistance. Conclusions: Ooitabi extract can lower blood pressure and improve lipid abnormalities and has likely contributed to the well‐known health and longevity of the population in Okinawa. [ABSTRACT FROM AUTHOR]

Droplet-based microfluidic technologies for encapsulating single cells have rapidly evolved into powerful tools for single-cell analysis. In conventional passive single-cell encapsulation techniques, because cells arrive randomly at the droplet generation section, to encapsulate only a single cell with high precision, the average number of cells per droplet has to be decreased by reducing the average frequency at which cells arrive relative to the droplet generation rate. Therefore, the encapsulation efficiency for a given droplet generation rate is very low. Additionally, cell sorting operations are required prior to the encapsulation of target cells for specific cell type analysis. To address these challenges, we developed a cell encapsulation technology with a cell sorting function using a microfluidic chip. The microfluidic chip is equipped with an optical detection section to detect the optical information of cells and a sorting section to encapsulate cells into droplets by controlling a piezo element, enabling active encapsulation of only the single target cells. For a particle population including both targeted and non-targeted particles arriving at an average frequency of up to 6000 particles per s, with an average number of particles per droplet of 0.45, our device maintained a high purity above 97.9% for the single-target-particle droplets and achieved an outstanding throughput, encapsulating up to 2900 single target particles per s. The proposed encapsulation technology surpasses the encapsulation efficiency of conventional techniques, provides high efficiency and flexibility for single-cell research, and shows excellent potential for various applications in single-cell analysis.

Despite the revolutionary success of chimeric antigen receptor (CAR)-T therapy for hematological malignancies, successful CAR-T therapies for solid tumors remain limited. One major obstacle is the scarcity of tumor-specific cell-surface molecules. One potential solution to overcome this barrier is to utilize antibodies that recognize peptide/major histocompatibility complex (MHCs) in a T cell receptor (TCR)-like fashion, allowing CAR-T cells to recognize intracellular tumor antigens. This study reports a highly specific single-chain variable fragment (scFv) antibody against the MAGE-A4 p230-239 /human leukocyte antigen (HLA)-A∗02:01 complex (MAGE-A4 pMHC), screened from a human scFv phage display library. Indeed, retroviral vectors encoding CAR, utilizing this scFv antibody as a recognition component, efficiently recognized and lysed MAGA-A4 + tumor cells in an HLA-A∗02:01-restricted manner. Additionally, the adoptive transfer of T cells modified by the CAR-containing glucocorticoid-induced tumor necrosis factor receptor (TNFR)-related receptor (GITR) intracellular domain (ICD), but not CD28 or 4-1BB ICD, significantly suppressed the growth of MAGE-A4 + HLA-A∗02:01 + tumors in an immunocompromised mouse model. Of note, a comprehensive analysis revealed that a broad range of amino acid sequences of the MAGE-A4p 230-239 peptide were critical for the recognition of MAGE-A4 pMHC by these CAR-T cells, and no cross-reactivity to analogous peptides was observed. Thus, MAGE-A4-targeted CAR-T therapy using this scFv antibody may be a promising and safe treatment for solid tumors., Competing Interests: Declaration of interests M.M. and Y.K. are employees of Sony Group Corporation, which collaborated in the development of a closed-cell isolation system. The Department of Personalized Cancer Immunotherapy, Mie University Graduate School of Medicine, is an endowment department supported by a grant from T cell Nouveau., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

By analyzing patients treated with adoptive immune cell therapies, various immune cell phenotypes have been found in the starting and infused materials as determinants of sustained remission. The isolation of these specific phenotypes for clinical use requires current Good Manufacturing Practice (cGMP)-compliant cell-sorting technologies with multiparameter selection capabilities. Here, we developed a cGMP-requirement-applicable fully closed cell sorter that has a suction mechanism and multiparameter detection using two laser optical settings. Negative pressure generated by a change in the chamber volume at a sorting point allows the isolation of cells of interest with high viability and purity. Our study demonstrated that this microfluidic sorter enables the isolation of cells of interest at an effective rate of 7,000 sorts per second on average. A purity of 85.5% and 77.1% effective yield with 93.7% viability was obtained when applying a target population of 35.9% in total (lymphocyte+CD8+) at 15,000 events per second (2 × 10 7 cells/mL). The sorted gene-modified T cells maintain largely unaltered proliferation, antigen recognition, cytokine release, and cytotoxicity functionalities., Competing Interests: The authors declare no competing interests., (© 2023 The Author(s).)

Affinity analysis using Hansen solubility parameters (HSP) reveals that the gel-sol transition point of binary organogels is correlated with preferential interactions between the solvophilic moiety of gelators and solvents. The decomposition of gelators in HSP analysis can be effectively used for predicting the thermal stability of gels.

The relationship between dehydration of polymer chains and the nanodroplet formation through the macroscopic liquid-liquid phase separation (LLPS) has been investigated for the aqueous solution of stereocontrolled poly( N -isopropylacrylamide) (PNiPAm) and poly( N -diethylacrylamide) (PNdEAm). The fluorescent probe method reveals that the temperature range of dehydration for PNiPAm chains is much narrower than that for PNdEAm. The sharp dehydration of polymer chains may give rise to the characteristic thermoresponsive behavior of PNiPAm in water. For meso-rich PNiPAms, the dehydration point ( T dh ), which is defined as the temperature where the single chains start assembling in the solution, locates far from the cloud point ( T c ). That is, the dehydration of the chain occurs antecedently before the system undergoes a macroscopic LLPS. For PNdEAm, however, the dissociation between T dh and T c is not found. For the aqueous solution of PNiPAm with 52% of the meso content, the fluorescence correlation spectroscopy has revealed that nano-order droplets (ca. 45 nm of the hydration radius) are stabilized in the intermediate state between T dh and T c . The sharp dehydration of PNiPAm chains may enable an acute condensation of polymers in droplets, causing a viscoelastic hindrance in the coalescence of droplets.

Near-infrared (NIR) spectra of phenol in a series of non-aromatic and aromatic solvents were recorded to study the competition between various types of solute-solute and solute-solvent interactions. Depending on the phenol concentration, the free OH and OH involved in the OH⋯OH interactions in the dimers and higher associates are present in cyclohexane solutions. On the other hand, free OH does not appear in Cl-containing solvents since at a low phenol content the OH groups participate in the OH⋯Cl interactions. In CCl 4 and tetrachloroethylene this interaction is weak, while in chlorobenzene the strength of this interaction is higher. In the aromatic solvents the solute-solute OH⋯OH interactions compete with the solute-solvent OH⋯π and aromatic CH⋯OH ones. Consequently, the degree of self-association of phenol in aromatic solvents is smaller than that in non-aromatic ones. The strength of the OH⋯π interactions increases with growing electron-donating ability of the substituents in the benzene derivatives. This observation obtained from the NIR spectra is in line with the results of the theoretical calculations (DFT). A clear correlation appears between the number of methyl groups in aromatic solvents and the population of the free OH groups. The methyl groups are steric hindrances and impede the formation of the OH⋯OH and OH⋯π interactions. Our results suggest the presence of aromatic CH⋯OH solute-solvent interactions, not observed in previous studies. NIR spectroscopy appears to be a powerful tool for exploration of free and weakly-bonded OH groups.

Background: It has been hypothesized that flavonoid ingestion stimulates immunity, promotes health, and prevents human illness. The aim of this analysis was to evaluate the association of the levels of immunoglobulin A (IgA) with the prevention of influenza infections and with the polyphenols contained in Okinawan vegetables., Methods: IgA, immunoglobulin G (IgG), immunoglobulin M (IgM), and soluble interleukin-2 receptor (sIL-2R) levels were measured in 44 outpatients who regularly ingested vegetables grown on Okinawa Island (200-300 g/day for ≥ 300 days/year) with no history of influenza infection and in 73 patients who ingested the vegetables irregularly or not at all with a history of influenza infection., Results: The patients who regularly ate Okinawan vegetables had higher IgA, IgG, and IgM levels than those who did not. On the other hand, patients who did not consume Okinawan vegetables and had influenza had lower IgA, IgG, and IgM levels. In addition, the IgA and IgG levels showed significant positive correlations with the sIL-2R levels in both groups., Conclusions: It may be beneficial to eat vegetables abundant in polyphenols every day. Secretory IgA antibodies are an important part of the immune defense against viral diseases. People who ingest Okinawan vegetables have high IgA levels and might be more likely to develop immunity against influenza RNA viruses.

Purpose: Fractographic analysis has been used to investigate the fracture behavior of Computer-aided design/computer-aided manufacturing (CAD/CAM) composite crowns by subjecting them to compression tests. However, it is difficult to investigate details of the fracture, including its initiation and propagation, using in vitro tests. The aim of this study was to determine the fracture origins and the order of crack initiation of CAD/CAM composite crowns using in silico nonlinear dynamic finite element analysis (FEA)., Material and Methods: The following materials were used: Cerasmart (CS), Katana Avencia Block (KA), and Shofu Block HC (HC) as CAD/CAM crowns, Panavia SA Cement Plus (SA) as a luting material, and Clearfil DC Core Plus (DC) as an abutment. The elastic moduli and fracture strain of each material were obtained from the stress-strain curve of in vitro three-point bending tests. The fracture origins and order of crack initiation of the materials were determined by in silico nonlinear dynamic compression analysis. Load-displacement curves were statistically compared with the results of the in vitro compression tests (Pearson's correlation test, α = 0.05)., Results: The nonlinear dynamic FEA demonstrated that crack initiation was primarily observed near the lingual side of the CAD/CAM crowns and immediately propagated to the central fossa. The models were fractured following the in vitro fracture strains, showing the same order for the products tested (CS/KA/HC, SA, and DC). Load-displacement curves with the use of CS, KA, and HC were significantly correlated to the corresponding in vitro compression tests results (CS: r = 0.985, p < 0.05, KA: r = 0.987, p < 0.05, and HC: r = 0.997, p < 0.05)., Conclusions: The in silico model established in this study clarified the crack initiation of the CAD/CAM composite crowns and the order of crack initiation among the investigated products, suggesting that the present approach is useful for analyzing the fracture behavior of CAD/CAM composite crowns in detail., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Thermoresponsive phase separation mechanisms of aqueous poly( N -isopropylacrylamide) (PNIPAM) solutions were investigated using an optical tweezer combined with a Raman microspectroscope. A near-infrared laser beam (λ = 1064 nm) was focused into the solution to produce and trap a single polymer microdroplet under an optical microscope. The laser beam played two important roles: The first role is to locally heat the solution to induce phase separation in which numerous polymer microdroplets are generated around the focus, while the second one is to collect these microdroplets. Eventually, a single polymer droplet was stably produced and trapped at the focus. Our method enabled us to perform two types of microanalysis for the droplet. Analysis I is real-time monitoring the growth of the polymer droplets by which we can determine the growth rate of droplets. Analysis II is Raman microspectroscopy to reveal chemical components of the droplets. By means of these two analyses, we revealed important phase separation mechanisms in terms of stereoregularity (isotacticity) dependence. From analysis I, we show that droplet growth is governed by the Ostwald ripening mechanism and the growth is accelerated by increasing the isotacticity. From analysis II, we show that the gelation is promoted in the droplet (physical gel formation) with increasing isotacticity. Our technique should be a versatile tool to explore liquid-liquid phase separation mechanisms for various binary solution systems.

A poly(ethylene oxide) (PEO)-poly(propylene oxide) (PPO) alternating multiblock (AMB) copolymer with various molecular weights was prepared via precipitation fractionation from an acetone/n-hexane mixture. The cloud point (T c ) of the aqueous solution of PEO-PPO AMB copolymer decreased as the number-average molecular weight of the sample increased. This phenomenon is generally observed for certain homopolymer systems having a lower critical solution temperature, such as PEO/water and poly(N,N-diethylacrylamide)/water systems. The relationship between the T c of the solutions and the number of monomer units of the AMB copolymer suggests that the Shultz-Flory theory is applicable to this system.

Trimethylamine N-oxide is found to be effective in regulating the interaction between microtubules and kinesins over a wide temperature range. The lifetime of the motility of microtubules on kinesins at high temperatures is prolonged using trimethylamine N-oxide. The activation energy of microtubule motility is increased by trimethylamine N-oxide. Prolonged operation at high temperatures decreased the activation energy of MT motility despite the increase in concentration of trimethylamine N-oxide.

mRNA degradation is an important cellular mechanism involved in the control of gene expression. Several genome-wide profiling methods have been developed for detecting mRNA degradation in plants and animals. However, because many of these techniques use poly (A) mRNA for library preparation, degradation intermediates are often only detected near the 3'-ends of transcripts. Previously, we developed the Truncated RNA End Sequencing (TREseq) method using Arabidopsis thaliana, and demonstrated that this method ameliorates 3'-end bias. In analyses using TREseq, we observed G-rich sequences near the 5'-ends of degradation intermediates. However, this finding remained to be confirmed in other plant species. Hence, in this study, we conducted TREseq analyses in Lactuca sativa (lettuce), Oryza sativa (rice) and Rosa hybrida (rose). These species including A. thaliana were selected to encompass a diverse range in the angiosperm phylogeny. The results revealed similar sequence features near the 5'-ends of degradation intermediates, and involvement of translation process in all four species. In addition, homologous genes have similar efficiencies of mRNA degradation in different plants, suggesting that similar mechanisms of mRNA degradation are conserved across plant species. These strong sequence features were not observed in previous degradome analyses among different species in plants., (� The Author(s) 2019. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

We studied the dependence on tacticity of the dynamic phase separation behavior of thermoresponsive poly( N, N-diethylacrylamide) (PDEA) in an aqueous solution. Using a laser temperature-jump technique combined with transient photometry, we determined the time constants of the phase separation and found that both atactic and isotactic-rich PDEAs had fast and slow phase separation processes (τ fast and τ slow ). The fast process (τ fast ) was independent of the tacticity, irrespective of the concentration. On the other hand, the slow process had a strong dependence on the tacticity. We found the slow phase separation process got considerably faster with increasing isotacticity in dilute solutions. This effect due to the tacticity of the PDEA is totally different from that of poly( N-isopropylacrylamide) and can be explained on the basis of the difference between the hydrophobicity of atactic PDEA and that of isotactic-rich PDEA.

Thermal changes in the association behavior of poly(ethylene oxide)-poly(propylene oxide) alternating multiblock (PEO-PPO AMB) copolymers in water are investigated by the use of transmittance and light scattering measurements. Two PEO-PPO AMB copolymers with a different weight fraction of PEO, (EO 220 PO 33 ) 8 and (EO 68 PO 33 ) 9 , are prepared. The weight-average molecular weights of (EO 220 PO 33 ) 8 and (EO 68 PO 33 ) 9 estimated by static light scattering measurements are 1.3 × 10 5 and 4.1 × 10 4 g mol -1 , respectively. The number of PEO-PPO repeating pairs is over 8. It is found that the aqueous solution of (EO 220 PO 33 ) 8 undergoes phase separation with a lower critical solution temperature (LCST) of around 58 °C at 0.3 wt %. For the aqueous (EO 68 PO 33 ) 9 solution, the LCST is estimated to be ca. 42 °C. The critical solution concentration for (EO 68 PO 33 ) 9 is not clear because of a small concentration dependence of T c at a higher concentration range. Dynamic light scattering measurements indicate that a micellelike aggregate is formed below the LCST. From the Debye plot, it is elucidated that the second virial coefficient, A 2 , starts going down at around 32 °C for (EO 220 PO 33 ) 8 and below 15 °C for (EO 68 PO 33 ) 9 . The A 2 value of (EO 220 PO 33 ) 8 approaches 0 near 50 °C, whereas that of (EO 68 PO 33 ) 9 approaches 0 at around 35 °C. At a high temperature, the attractive interaction among the copolymers becomes dominant, thereby inducing the formation of micellelike aggregates.

The dynamic and static phase separation behavior in aqueous poly(N-isopropylacrylamide) (PNIPAM) solutions is highly sensitive to the tacticity of PNIPAM. We investigated the phase separation dynamics of aqueous solutions of PNIPAM with different tacticities (atactic and syndiotactic-rich types) and found that the phase separation dynamics of syndiotactic-rich PNIPAM was much different from that of atactic-type PNIPAM. First, phase separation in syndiotactic-rich PNIPAM was faster. Second, there was a critical point (Ccp) in the concentration dependence of the phase separation rate: the phase separation accelerated dramatically when the solution concentration was higher than 2.0 wt % (= Ccp). Third, syndiotactic-rich PNIPAM required a higher thermal energy for phase separation compared to atactic PNIPAM. Such behavior can be explained on the basis of the high hydrophobicity of syndiotactic-rich PNIPAM in a dehydrated state and a diffusion-controlled aggregation model. The present study shows that precise control of the stereoregularity will open new channels toward the design and development of stimuli-responsive-polymer-based smart materials.

Molecular organogels, comprising small organic gelators in solvents, can be applied for dispersal of optical devices, such as emitters. Phenolic compounds and the surfactant bis(2-ethylhexyl) sulfosuccinate (AOT) are known examples of self-assembly organogels. However, conventional phenol + AOT gels in aromatic and acyclic alkane solvents are optically turbid, which is an obstacle for use as host materials in optical devices. In this study, a variety of aryl alcohol-AOT-solvent sets have been investigated systematically, and the correlation between the molecular architecture and optical transparency of the gels was considered. Accordingly, p-chlorophenol + AOT gels in cyclic alkane solvents were shown to form optically transparent gels. In contrast, aromatic and acyclic alkane solvents gave rise to turbid or opaque gels, even when utilizing the same gelators. AFM, NMR, SAXS, and FTIR were employed to determine the organogel structures. Consequently, we found that the gel transparency strongly depends on the size of the fibrous network of the gel, the structure of which is attributed to higher-order aggregates of the gelators. The average contour length and diameter of the fibrous network, lav and dav, respectively, were determined from AFM images. The transparent gels were shown to have lav = 4-9 μm and dav ≤ 0.3 μm, whereas the turbid gels had lav = 15 μm and dav = 0.4-0.6 μm. Such differences in the size of the fibrous network significantly affected the mechanical response of the gels, as shown by stress-strain measurements.

Bisporphyrin cleft molecule 1 Zn possessing a guest moiety assembled to form supramolecular polymers through host-guest interactions. Bispyridine cross-linkers created interchain connections among the supramolecular polymers to form networked polymers in solution. Solution viscometry confirmed that the cross-linked supramolecular polymers were highly entangled. Frequency-dependent linear viscoelastic spectroscopy revealed that the supramolecular polymers generated well-entangled solutions with associating and networking polymers, whereas the solid-like aggregates moved individually without breaking and reforming structures below the transition temperature of 9.6 °C. Morphological transition of the supramolecular polymers was evidenced by AFM images; the non-cross-linked polymer resulted in wide-spread thin networks, while the cross-linked networks produced thicker worm-like nanostructures. The supramolecular networks gelled in 1,1,2,2-tetrachloroethane, and an elastic free-standing film was fabricated with a Young's modulus of 1 GPa., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Poly(N-isopropylacrylamide) (PNiPAM) compounds with various diad tacticities were prepared, and the molecular interaction properties in a thin film deposited on a gold surface were analyzed using infrared spectroscopy. The intramolecular and intermolecular interactions were found to depend on the tacticity, and only atactic (diad ratio 46 %) PNiPAM exhibits poor molecular interaction even in the bulk sample. On the other hand, the same series of compounds dissolved in an acetone solution were spread on a gold surface to form a thin film. In the dissolution process, the polymer molecules are relaxed via solvation, and they are bound to the gold surface by a molecular interaction to form a submonolayer thin film. In the thin film, the molecular interaction with the gold surface via the N-H group was monitored in the infrared spectra only for a nearly isotactic (m = 90) PNiPAM by an apparent shift of the N-H stretching vibration band. This shift was confirmed by changing the degree of hydrophilicity of the gold surface: a larger shift is found on a gold surface with stronger hydrophilicity. As a result, the conformation of a nearly isotactic molecule is found to be extended by the interaction with the gold surface, which works to immobilize the molecule.

Chrysanthemums (Chrysanthemum×morifolium Ramat.) are an important cut-flower and potted plant crop in the horticultural industry world wide. Chrysanthemums express the flavonoid 3'-hydroxylase (F3'H) gene and thus accumulate anthocyanins derived from cyanidin in their inflorescences which appear pink/red. Delphinidin-based anthocyanins are lacking due to the deficiency of a flavonoid 3', 5'-hydroxylase (F3'5'H), and so violet/blue chrysanthemum flower colors are not found. In this study, together with optimization of transgene expression and selection of the host cultivars and gene source, F3'5'H genes have been successfully utilized to produce transgenic bluish chrysanthemums that accumulate delphinidin-based anthocyanins. HPLC analysis and feeding experiments with a delphinidin precursor identified 16 cultivars of chrysanthemums out of 75 that were predicted to turn bluish upon delphinidin accumulation. A selection of eight cultivars were successfully transformed with F3'5'H genes under the control of different promoters. A pansy F3'5'H gene under the control of a chalcone synthase promoter fragment from rose resulted in the effective diversion of the anthocyanin pathway to produce delphinidin in transgenic chrysanthemum flower petals. The resultant petal color was bluish, with 40% of total anthocyanidins attributed to delphinidin. Increased delphinidin levels (up to 80%) were further achieved by hairpin RNA interference-mediated silencing of the endogenous F3'H gene. The resulting petal colors were novel bluish hues, not possible by hybridization breeding. This is the first report of the production of anthocyanins derived from delphinidin in chrysanthemum petals leading to novel flower color.

The stereochemistry around the N-benzoylated indole moiety of indometacin was studied by restricting the rotation about the N-C7' and/or C7'-C1' bond. In the 2',6'-disubstituted ones, an atropisomeric property was found and the atropoisomers were separated and isolated as stable forms. Their biological abilities to inhibit cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) were examined. Only the aR-isomer showed specific inhibition of COX-1, and COX-2 was not inhibited by either atropisomer. Conformational analysis in NMR studies and X-ray crystallography, and CD spectra in combination with calculations were utilized to elucidate the bioactive conformations., (Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

We investigated the relationship between the elastic modulus, G and the reaction probability, p for polymer networks. First, we pointed out that the elastic modulus is expressed by G = {(fp∕2 - 1) + O((p - 1)(2))} Nk(B)T∕V (percolated network law), which does not depend on the local topology of the network structure or the existence of the loops. Here, N is the number of lattice point, V is the system volume, f is the functionality of the cross-link, k(B) is the Boltzmann constant, and T is the absolute temperature. We also conducted simulations for polymer networks with triangular and diamond lattices, and mechanical testing experiments on tetra-poly(ethylene glycol) (PEG) gel with systematically tuning the reaction probability. Here, the tetra-PEG gel was confirmed to be a potential candidate for ideal polymer networks consisting of unimodal strands free from defects and entanglements. From the results of simulations and experiments, it was revealed, for the first time, that the elastic modulus obeys this law in the wide range of p (p(c) ≪ p ≤ 1), where p(c) is the reaction probability at gelation threshold.

Circular dichroism (CD) spectra of the 2,2'-binaphthyl ester derived from Δ(5)-sterols showed not bisignate CD but diagnostic CD bands at around 210 and 240 nm. These bands might be attributable to an interaction between an olefinic chromophore and a binaphthyl one. Various types of unsaturated sterols were thus derivatized followed by complete hydrogenation, to give saturated sterols. As a result, CD spectra of the binaphthyl derivatives of the saturated sterols showed bisignate curves centered at 240 nm (3S(β): positive chirality; 3R(α): negative one). This suggested a straightforward and practical method for discriminating the absolute stereogenic center at the C-3 positions of sterols based on an induced CD. This finding should contribute significantly to the analysis of metabolites of various types of sterols., (Copyright © 2012 Elsevier Inc. All rights reserved.)

A microsensor that can continuously measure the deformability of a single red blood cell (RBC) in its microchannels using microelectrodes is described in this paper. The time series of the electric resistance is measured using an AC current vs. voltage method as the RBC passes between counter-electrode-type micro-membrane sensors attached to the bottom wall of the microchannel. The RBC is deformed by the shear flow created in the microchannel; the degree of deformation depends on the elastic modulus of the RBC. The resistance distribution, which is unique to the shape of the RBC, is analyzed to obtain the deformability of each cell. First, a numerical simulation of the electric field around the electrodes and RBC is carried out to evaluate the influences of the RBC height position, channel height, distance between the electrodes, electrode width, and RBC shape on the sensor sensitivity. Then, a microsensor was designed and fabricated on the basis of the numerical results. Resistance measurement was carried out using samples of normal RBCs and rigidified (Ca(2+)-A23186 treated) RBCs. Visualization measurement of the cells' behavior was carried out using a high-speed camera, and the results were compared with those obtained above to evaluate the performance of the sensor.

We report three cases of patients in their eighties who received anti-EGFR antibody mono-therapy as first-line treatment for metastatic colorectal cancer. CASE 1: An 86-year-old woman who received cetuximab after a colostomy for unresectable rectal cancer with synchronous liver and lung metastases. Serum levels of CEA and CA19-9 showed a significant decrease at 2 months, after which they showed a gradual increase. Computed tomography (CT) revealed a reduction in the rectal tumor. CASE 2: An 82-year-old woman who received cetuximab for peritoneal metastases after a transverse colectomy. Serum levels of CEA and CA19-9 decreased to normal levels at 2 months, and CT imaging revealed disappearance of the tumor in the peritoneal cavity. CASE 3: A 79-year-old man who received panitumumab for lung, liver and para-aortic lymph node metastases after a descending colectomy. Serum levels of CEA and CA19-9 showed a decrease at 1 month, after which they showed a gradual increase. No marked change in the tumor was observed by CT. No change was observed in performance status or Vulnerable Elders Survey( VES-13) score, and the effect on overall condition was minimal. Grade 1-2 acneiform skin rash, paronychia, and desquamation, and grade 2-3 dry skin and pruritis were observed. More precise instructions on measures for dealing with skin rash are necessary to obtain higher drug compliance.

We report the experimentally determined phase diagram for an aqueous solution of isotactic-rich poly(N-isopropylacrylamide) (PNiPAM) composed of the sol-gel transition curve and the cloud-point curve. The meso diad content of isotactic-rich PNiPAM is 64%, and it is soluble in water at low temperatures, but undergoes a sol-to-gel transition with increasing temperature in the investigated concentration range of 1.8 wt. %-6.0 wt. %. With a further increase in temperature, the system becomes turbid. The gel formation and clouding behavior are thermally reversible. This is the first observation of thermoreversible gelation under the cloud-point temperature for an aqueous solution of PNiPAM. On the basis of the determined phase diagram, we carried out light scattering experiments to characterize the sol-gel transition behavior as a function of temperature.

We present dielectric coagulometry as a new technique to estimate the risk of venous thrombosis by measuring the permittivity change associated with the blood coagulation process. The method was first tested for a simple system of animal erythrocytes suspended in fibrinogen solution, where the coagulation rate was controlled by changing the amount of thrombin added to the suspension. Second, the method was applied to a more realistic system of human whole blood, and the inherent coagulation process was monitored without artificial acceleration by a coagulation initiator. The time dependence of the permittivity at a frequency around 1 MHz showed a distinct peak at a time that corresponds to the clotting time. Our theoretical modeling revealed that the evolution of heterogeneity and the sedimentation in the system cause the peak of the permittivity.

The wavenumber shift in the CD stretching (ν(CD)) band of the monodeuterated methanol (CH(2)DOH) has been monitored in water-methanol mixtures. For the pure liquid, two dominant bands are observed at 2148 and 2176 cm(-1) in the ν(CD) region. The matrix isolation technique and spectral simulation based on quantum chemical calculations have revealed that these two bands are categorized into the C(1) mode and originate from methanol molecules participating in different hydrogen(H)-bonding patterns. The simulation results for methanol clusters have suggested that the 2148 cm(-1) band is concerned with the end-donor species in the H-bonding network. The relative intensity of the band near 2148 cm(-1) decreases with increasing water concentration, indicating that the population of the end-donor species decreases by the addition of water. This spectral change causes the blue shift in the mean center of the ν(CD) band of CH(2)DOH in water.

Analytical results of a series of poly(N-isopropylacrylamide) (PNiPA) with different tacticities using infrared spectroscopy are presented for studying the influence of the solvation and molecular interactions between the polymeric chains. Infrared spectra of solid matter samples of the compounds exhibit a systematic band intensity change for three band components at 1,680, 1,659, and 1,628 cm(-1) involved in the amide I band. The three components correspond to the free, half, and full hydrogen bondings of the secondary amide group, which reflect the molecular configuration depending on the tacticity. When cast films of the compounds prepared on a solid surface are analyzed by infrared transmission spectrometry, another factor of the solvent used for the film preparation is found to be another factor which plays an important role in determining the molecular architecture in the films. This molecular imprint mechanism after the solvation is confirmed by measuring infrared multiple-angle incidence resolution spectra of annealed films. The molecular interactions in the polymeric samples have been revealed by the use of infrared spectroscopy and the tacticity-controlled samples.

A straightforward strategy is reported for chiral discrimination in a specified carotenoid using a CD band, which is insensitive to conformational changes, computed by quantum chemical calculation.

Cetuximab (Erbitux) is a targeted therapy that used to treat metastatic colorectal cancer. It is classified as a "monoclonal antibody" and "signal transduction inhibitor" by binding to epidermal growth factor receptors (EGFR). We report 6 patients who responded well to cetuximab out of 8 patients with recurrent/advanced colorectal cancer who have received the drug at our hospital since November 2008. Four patients were men and 2 were women, with their ages ranging from 48 to 77 years. The primary cancers were located in the rectum (n=1), sigmoid colon (n=4), and ascending colon (n=1). Performance status (PS) was 0-1. These patients were treated with cetuximab as second-line (n=1), third-line (n=3), fifth-line (n=1), or seventh-line (n=1) therapy. Three patients received cetuximab monotherapy, while the other 3 were given CPT-11 (150 mg/m2, every 2 weeks) as concomitant therapy. Among the 3 patients receiving combination therapy, 2 patients had already received treatment with FOLFIRI. Even in the cetuximab monotherapy group, a partial response (PR) was observed in 2 patients, demonstrating a strong cytoreductive effect. Tumor markers also showed large decreases, with the percent decrease at 1 month being 31.7% and 60.8% in the monotherapy and combination therapy groups, respectively, while it was respectively 14.1% and 29.5% at 2 months. The mean progression-free survival (PFS) time and the time to treatment failure (TTF) were respectively 3.0 months and 4.5 months in the monotherapy group versus 7.3 months and 9.3 months in the combination therapy group. Acneiform rash and paronychia occurred in all 6 patients.

Although it has been suggested that the tacticity affects the hydrophilicity of poly(N-isopropylacrylamide) (PNiPA), little is known about the physical background of this phenomenon. In this study, we investigated the solubility of the dimer model compounds (DNiPA). The partition coefficient of DNiPA in the two phases of a water/chloroform mixture has indicated that DNiPA with the racemo configuration (r-DNiPA) is more soluble in water than DNiPA with the meso configuration (m-DNiPA). The difference of the hydration free energy between m- and r-DNiPA is estimated to be 1.2 kJ mol(-1). The molecular mechanics (MM) calculations with the GB/SA model have revealed that r-DNiPA in water is more stable by ca. 1 kJ mol(-1) than m-DNiPA, which is in excellent agreement with the experimental result. The MM calculations have also indicated that the intramolecular interaction of m-DNiPA is stronger than that of r-DNiPA, while r-DNiPA is advantageous in terms of the hydration free energy and conformational entropy.