Rational Design and Synthesis of HSF1-PROTACs for Anticancer Drug Development

PROTACs employ the proteosome-mediated proteolysis via E3 ligase and recruit the natural protein degradation machinery to selectively degrade the cancerous proteins. Herein, we have designed and synthesized heterobifunctional small molecules that consist of different linkers tethering KRIBB11, a HSF1 inhibitor, with pomalidomide, a commonly used E3 ligase ligand for anticancer drug development.     

Atomic structure of the Si(5 5 12)-2 × 1 surface

Based on the results of scanning tunneling microscopy studies of the reconstructed Si(5 5 12)-2 × 1 surface, its atomic structure has been found. It turns out that Si(5 5 12)-2 × 1 consists of four one-dimensional structures: honeycomb (H) chain, π-bonded H′ (π) chain, dimer-adatom (D/A) row, and tetramer (T) row. Its period is composed of three subunits, i.e., (i) (3 3 7) unit with a D/A row [D(3 3 7)], (ii) (3 3 7) unit with a T row [T(3 3 7)], and (iii) (2 2 5) unit with both a D/A and a T row. Two kinds of adjacent subunits, T(3 3 7)/D(3 3 7) and D(3 3 7)/(2 2 5), are divided by H chains with 2× periodicity due to buckling, while one kind of adjacent subunits, T(3 3 7)/(2 2 5), is divided by a π chain with 1× periodicity. Two chain structures, H and π chains, commute with each other depending upon the external stresses perpendicular to the chain, which is the same for two row structures, D/A and T rows. It can be concluded that the wide and planar reconstruction of Si(5 5 12)-2 × 1 is originates from the stress balance among two commutable chains and two commutable rows.     

Development of a miniature double-pass cylindrical mirror electron energy analyzer (DPCMA), and its application to Auger photoelectron coincidence spectroscopy (APECS)

We have developed a miniature double-pass cylindrical mirror electron energy analyzer (DPCMA) with an outer diameter of 26 mm. The DPCMA consists of a shield for the electric field, inner and outer cylinders, two pinholes with a diameter of 2.0 mm, and an electron multiplier. By assembling the DPCMA in a coaxially symmetric mirror electron energy analyzer (ASMA) coaxially and confocally we developed an analyzer for Auger photoelectron coincidence spectroscopy (APECS). The performance was estimated by measuring the Si-LVV-Auger Si-1s-photoelectron coincidence spectra of clean Si(1 1 1). The electron-energy resolution of the DPCMA was estimated to be E/ΔE = 20. This value is better than that of the miniature single-pass CMA (E/ΔE = 12) that was used in the previous APECS analyzer.     

Transflective liquid-crystal display using low-twisted vertically aligned mode

We present the design of a transflective and low-power LCD using a low-twist vertically aligned liquid crystal (LC) cell, achieved by blending a chiral additive with a patterned reflector in a single-domain configuration. Unlike the conventional single-domain transflective LCD, in which it is possible to optimize only one of the transmissive and reflective regions, the device suggests that it is possible to optimize both the transmission and reflection design to obtain favorable results in both reflective and transmissive light conditions by optimizing the chiral pitch and twist angle. From the parameter space diagram (PSD) method, which does not include the information on chiral pitch and the nonuniform LC director tilt angle, optimization focused on the transmissive region is performed. By analyzing the relation between the transmittance and the chiral pitch under the applied voltage, the optimized twist angle and chiral pitch are proposed. It is described that the optimized twist angle is also available for the reflective region by the dynamic PSD method by considering the average tilt angle under applied voltage.     

Long range disorder and Anderson transition in systems with chiral symmetry

We study the spectral properties of a chiral random banded matrix (chRBM) with elements decaying as a power-law H_ij|i−j|⁻. This model is equivalent to a chiral 1D Anderson Hamiltonian with long range power-law hopping. In the weak disorder limit we obtain explicit nonperturbative analytical results for the density of states (DoS) and the two-level correlation function (TLCF) by mapping the chRBM onto a nonlinear σ model. We also put forward, by exploiting the relation between the chRBM at =1 and a generalized chiral random matrix model, an exact expression for the above correlation functions. We give compelling analytical and numerical evidence that for this value the chRBM reproduces all the features of an Anderson transition. Finally we discuss possible applications of our results to quantum chromodynamics (QCD).     

Investigating magnetorheological properties of a mixture of two types of carbonyl iron powders suspended in an ionic liquid

In this work, properties of a magnetorheological (MR) fluid, prepared by dispersing a mixture of two types of carbonyl iron powders (CIPs) of different sizes, in an ionic liquid (N,N-diethyl-N-methyl-N-(2-methoxyethyl) ammonium tetrafluoroborate) that is stable from 9 °C to ca. 300 °C, have been investigated. At first, the random packing density of the mixture was computed as function of mixing ratio of CIP, in order to find out the tendency of the variation. Next, several mixtures, all having the same weight, were prepared at various mixing ratios and dispersed in the ionic liquid, in order to experimentally find the most suitable mixing ratio of CIP. Then, the magnetic clusters of the synthesized MR fluids were observed by using a digital microscope equipped with two permanent magnets, whereas the MR properties were investigated by using a rotation viscometer equipped with a solenoid coil. The experimental results pointed out that the MR fluid with 60 wt% fraction of large particles exhibited the highest MR response.     

Synthesis of Seven-Membered Benzolactones by Nickel-Catalyzed C−H Coupling of Benzamides with Oxetanes

A NiCl₂(PEt₃)₂-catalyzed regioselective C−H coupling of 8-aminoquinoline-derived benzamides with oxetanes has been developed. The reaction proceeds with concomitant removal of the 8-aminoquinoline auxiliary to directly form the corresponding seven-membered benzolactones, which frequently occur in natural products and bioactive molecules. Additionally, no stereochemical erosion is observed during the course of the reaction, and the use of enantioenriched and substituted oxetane thus provides a new avenue to the optically active benzolactone.     

A micrometer head integrated microfluidic device for facile droplet size control and automatic measurement of a droplet size

A novel microfluidic droplet generator is proposed, which can control the droplet size through turning an integrated micrometer head with ease, and the size of the produced micro-droplet can be automatically and real-time monitored by an open-sourced software and off-the-shelf hardware.     

Study of alkyl chain length dependent characteristics of imidazolium based ionic liquids [CnMIM]+[TFSA]− by Brillouin and dielectric loss spectroscopy

This study examined the acoustic phonon mode of ionic liquids consisting of 1-alkyl-3-methyl-imidazolium family (C_nMIM) cations with n values ranging from 2 to 10 and bis(trifluoromethylsulfonyl)amide (TFSA) anion in the temperature range from 300 K to 100 K. [C_nMIM]⁺[TFSA]^? showed depolarized (VH) components of Brillouin peaks at temperatures below the glass transition temperature when n is larger than 4. On the other hand, in the case of ionic liquids with different anions, such as [C₄MIM]⁺[BF₄]^?, [C₄MIM]⁺[PF₆]^? and [C₈MIM]⁺[BF₄]^?, the VH component of Brillouin peaks was not observed in the temperature range investigated. The dielectric loss spectra showed that the temperature dependence of alkyl chain domain relaxation of all ionic liquids followed the Arrhenius law and showed an increase in activation energy at the temperature where the VH component of Brillouin peak appeared. These results suggest that the observed depolarized component of Brillouin peak might originate from uniquely induced polarization in the 2nd domain composed of head groups of cations and anions.     

Surface structure of low-coveraged Cs on Si(0 0 1)-() system

Alkali metals (AM) on semiconductors have been investigated as a simple model system for the metal-semiconductor interfaces due to their simple electronic structures. Especially, cesium (Cs) on Si(0 0 1) surface has been studied with various experimental techniques. In this study, we investigated the atomic structure of initial Cs adsorption on Si(0 0 1)-(2×1) surface using coaxial impact collision ion scattering spectroscopy. When Cs atoms are adsorbed on Si(0 0 1)-(2×1) up to 0.2 ML at room temperature, the initial adsorption site is on-top T3 site with poor periodicity and the length of Si dimer is reserved as in the clean Si(0 0 1) surface. It is also found that Cs atoms adsorbed on Si(0 0 1) surface with a height of 2.83±0.05 Å from the second layer of Si(0 0 1) surface.