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Oligomers of the amyloid β (Aβ) protein play a critical role in the pathogenesis of Alzheimer's disease. However, their heterogeneity and lability deter the identification of their tertiary structures and mechanisms of action. Aβ trimers and Aβ dimers may represent the smallest aggregation unit with cytotoxicity. Although propeller-type trimer models of E22P-Aβ40 tethered by an aromatic linker have recently been synthesized, they unexpectedly exhibited little cytotoxicity. To increase the flexibility of trimeric propeller-type models, we designed and synthesized trimer models with an alkyl linker

We propose a site-specific inhibition of Aβ42 oligomerization by the green perilla-derived chalcone DDC, which is converted to its decomposed flavonoids (1–3) via nucleophilic aromatic substitution with water molecules, in vitro and in vivo.

Since amyloid β (Aβ) oligomers are more cytotoxic than fibrils, various dimer models have been synthesized. We focused on the C-terminal region that could form a hydrophobic core in the aggregation process and identified a toxic conformer-restricted dimer model (E22P,G38DAP-Aβ40 dimer) with an l,l-2,6-diaminopimelic acid linker (

The electronic, lattice, and magnetic properties of CoSb3, Cr-doped CoSb3, and related compound thin films were calculated by using the total energy pseudopotential method. A vacuum region and slab as a thin film were periodically repeated in the supercell. We considered three slab structures. One is symmetric, another is asymmetric, and the third is unusual. They are free-standing in the supercell. The magnetic moment of doped Cr atom is large in all Cr-doped cases. Magnetic moments of several Co atoms are enhanced in the asymmetric and unusual cases. The calculation results in this study indicate that electronic states of most thin films are ferromagnetic and they are energetically more favorable than nonmagnetic cases.

Therapeutic oligonucleotides have molecular weights of more than 6000 Da. They typically contain chemically modified structures such as phosphorothioate (PS) and a locked nucleic acid (LNA). To determine the effect of the length and chemical modification on the physicochemical properties, various nucleic acids with different lengths and modified structures were analyzed using traveling-wave ion mobility mass spectrometry (TWIMS).The physicochemical characteristics of the modified oligonucleotides were determined using IM-MS. Each oligonucleotide was evaluated by confirming the multivalent charge state drift times, collision cross-section (CCS) values, and CCS widths.By plotting the m/z for oligonucleotides of different lengths and the CCS values at each charge state, a bottoming-out shape plot at one charge per 4.0-3.5 bases was confirmed. Moreover, significant differences were observed in the CCS values between the PS-modified and unmodified oligonucleotides. The PS-modified oligonucleotide showed a wider CCS range that was proportional to the PS modification ratio of the oligonucleotide sequence.The TWIMS results showed a correlation between the length and modification of oligonucleotides and the CCS values. In addition, it suggested that each charge state of the oligonucleotide ion has different physicochemical properties.

It is known that the value of an object can be increased by forming an image of owning the object without actually possessing it. However, the detailed mechanism behind this phenomenon remains unknown. In this study, we conducted two experiments using newly created three-dimensional abstract objects to examine whether the formation of a mental image of ownership increases the value of an object when a participant has a haptic experience of the object. The results suggest that when participants’ mental visual imagery ability was relatively high, having a haptic experience increased the value of the object through their image of ownership. For others, however, imagining ownership lowered the value of the object. The results also indicate that obtaining spatial information about an object through a haptic experience increases the value of the object. This study suggests that haptic information about an object contributes to the mechanism modulating how the value of an object is influenced by individual differences in visuospatial imagery ability.

RNA aptamers have garnered attention for diagnostic applications due to their ability to recognize diverse targets. Oligomers of 42-mer amyloid β-protein (Aβ42), whose accumulation is relevant to the pathology of Alzheimer's disease (AD), are among the most difficult molecules for aptamer recognition because they are prone to aggregate in heterogeneous forms. In addition to designing haptens for in vitro selection of aptamers, the difficulties involved in determining their effect on Aβ42 oligomerization impede aptamer research. We previously developed three RNA aptamers (E22P-AbD4, -AbD31, and -AbD43) with high affinity for protofibrils (PFs) derived from a toxic Aβ42 dimer. Notably, these aptamers recognized diffuse staining, which likely originated from PFs or higher-order oligomers with curvilinear structures in a knock-in AppNL-G-F/NL-G-F mouse, carrying the Arctic mutation that preferentially induced the formation of PFs, in addition to a PS2Tg2576 mouse. To determine which oligomeric sizes were mainly altered by the aptamer, ion mobility-mass spectrometry (IM-MS) was carried out. One aptamer, E22P-AbD43, formed adducts with the Aβ42 monomer and dimer, leading to suppression of further oligomerization. These findings support the utility of these aptamers as diagnostics for AD.

We studied thin films of Fe2VAl, Fe2VAl/Si, and a related compound using the total energy pseudopotential method. The internal atoms in a supercell of the repeated slab model were fully relaxed, except for Fe2VAl/Si. The detailed electronic and magnetic properties of structurally relaxed thin films of Fe2VAl, Fe2VAl/Si, and a related compound were calculated. These films are free-standing in the supercell, except for Fe2VAl/Si, which comprises Fe2VAl and Si (substrate) layers in a supercell. A thin film comprising Fe2V, Al, and Si (substrate) layers in the supercell (denoted as Fe2V/Al/Si) was also studied. Although electronic states of bulk Fe2VAl (full-Heusler) are metallic with pseudo-gap states around the Fermi level and nonmagnetic, the calculation results for Fe2VAl, Fe2VAl/Si, and Fe2V/Al/Si thin films in this study indicate that the films have ferromagnetic properties and their ferromagnetic states are energetically more favorable than nonmagnetic states. The magnetic moments are large and enhanced in the thin films. The magnetic moments of Fe in Fe2VAl (Fe12V4Al4), Fe2VAl (Fe20V8Al8), Fe2VAl/Si, and Fe2V/Al/Si thin films are 2.07 μ B/per atom, 1.29 μ B/per atom, 1.83 μ B/per atom, and 2.22 μ B/per atom, respectively. Although thin films have net ferromagnetic properties, the magnetic moments of the up and down spin states of Fe and V are antiferromagnetically aligned.

In the Brazilian judiciary, the Electoral Registry Offices (EROs) are responsible for managing the Brazilian electoral districts. Moreover, not only do they organize elections in their district, but they are also responsible for managing the registration of electors and supervising the political parties. Brazil has a multi-party system with more than 35 political parties competing over the 295 cities of Santa Catarina state, which had over 4.98 million voters in 2017. In this context, we present a mixed integer model, with the concepts of goal programming and contiguity graph, to propose a more equilibrated distribution of political districts to Santa Catarina state. The mathematical model considers the political districting criteria (population balance, spatial contiguity, and compactness), and also considers the particularities of the Brazilian electoral system (minimum number of voters in an electoral district, maximum electoral zones per city, and so forth). The objective of the problem is to determine the optimum set of districts for the most efficient use of public resources and best service to the population. Therefore, there must be a balance of workload among the (EROs), i.e., a steady number of electors and nominating petitions per district. The solution proposed succeeded in presenting a set of districts with a better workload distribution while respecting all the districting criteria and the Brazilian legislation. Compared to the current situation, the model shows a reduction in the standard deviation of the electorate distribution per district of 7520 voters. The solution obtained by the proposed model for the Brazilian electoral system in the state of Santa Catarina may be used by any other of the 26 Brazilian states. The proposed model is a particularization of the classic political districting problem since it inserts complementary constraints to this classic problem from the operational research literature.

Glycan engineering of antibodies has received considerable attention. Although various endo-β- N-acetylglucosaminidase mutants have been developed for glycan remodeling, a side reaction has been reported between glycan oxazoline and amino groups. In this study, we performed a detailed characterization for antibody products obtained through enzymatic and nonenzymatic reactions with the aim of maximizing the efficiency of the glycosylation reaction with fewer side products. The reactions were monitored by an ultraperformance liquid chromatography system using an amide-based wide-pore column. The products were characterized by liquid chromatography coupled with tandem mass spectrometry. The side reactions were suppressed by adding glycan oxazoline in a stepwise manner under slightly acidic conditions. Through a combination of an azide-carrying glycan transfer reaction under optimized conditions and a bio-orthogonal reaction, a potent cytotoxic agent monomethyl auristatin E was site-specifically conjugated at N-glycosylated Asn297 with a drug-to-antibody ratio of 4. The prepared antibody-drug conjugate exhibited cytotoxicity against HER2-expressing cells.

Here, we report the first synthesis of quasi-stable trimer models of full-length Aβ40 with a toxic conformation using a 1,3,5-phenyltris-l-alanyl linker at position 34, 36, or 38. The only trimer to exhibit weak neurotoxicity against SH-SY5Y cells was the one which was linked at position 38. This suggests that such a propeller-type trimer model is not prone to forming oligomers with potent neurotoxicity, which is in contrast with its corresponding dimer model.

Novel pyrenocrown ethers having different ring sizes were synthesized, and change of fluorescence spectra was investigated upon addition of metal ions. By the addition of Li+ and Na+ ions to 10–2 M CH3CN solutions of pyreno-15-crown-5 ether (3), excimer/monomer ratio decreased with 3–4 nm longer wavelength shift. Upon addition of Mg2+ and Ba2+ ions to the solution of 3, excimer emission increased with 11–25 nm longer wavelength shift. On the other hand, when these metal ions were added to pyreno-18-crown-6 ether (4), the excimer/monomer ratio monotonically decreased. Addition of Pb2+ ion to solutions of 3 and 4 caused dramatic decrease of both monomer and excimer fluorescence intensity. Inspection of these results indicates that 3 forms 1:1 and 2:1 complexes with respective monovalent and divalent metal ions, whereas 4 forms 1:1 complexes with both monovalent and divalent metal ions. The 1:1 complexes of 3 with monovalent and divalent metal ions emit respective excimer and monomer fluorescence, whereas the 2:1 complexes of 3 emit excimer fluorescence. Monotonical decrease of fluorescence intensity by the addition Pb2+ is attributed to heavy atom effect.

This paper proposes the new system of the noise visualization to detect the propagation path on the board. If high-voltage noise enters an electronic equipment due to electro-static discharge (ESD), it may cause the malfunction of the semiconductor component. The ESD noise has the characteristic that the rise time is short, and the propagation path of the ESD noise leading to the malfunction is unclear. So there is a problem that it tends to fall into trial and error countermeasures. There is a method of measuring the propagation path of the ESD noise using a single probe while applying ESD to the measurement object many times. However, there is a possibility that parts are broken during the evaluation test, and the propagation path cannot be estimated accurately. Therefore, we developed the new system to visualize the ESD noise on the whole printed circuit board (PCB) by applying ESD once. From this evaluation result, it was confirmed that the prototyped noise visualization system was effective for measuring the ESD noise.

Protein persulfidation plays a role in redox signaling as an anti-oxidant. Dimers of amyloid β42 (Aβ42), which induces oxidative stress-associated neurotoxicity as a causative agent of Alzheimer's disease (AD), are minimum units of oligomers in AD pathology. Met35 can be susceptible to persulfidation through its substitution to homoCys residue under the condition of oxidative stress. In order to verify whether persulfidation has an effect in AD, herein we report a chemical approach by synthesizing disulfide dimers of Aβ42 and their evaluation of biochemical properties. A homoCys-disulfide dimer model at position 35 of Aβ42 formed a partial β-sheet structure, but its neurotoxicity was much weaker than that of the corresponding monomer. In contrast, the congener with an alkyl linker generated β-sheet-rich 8–16-mer oligomers with potent neurotoxicity. The length of protofibrils generated from the homoCys-disulfide dimer model was shorter than that of its congener with an alkyl linker. Therefore, the current data do not support the involvement of Aβ42 persulfidation in Alzheimer's disease.

Organic field-effect transistors with ionic liquids have attracted much attention, since the ionic liquids induce an intense electric field at a semiconductor interface, resulting in a high concentration of charge carriers. It is expected that such strong electric fields and highly doped charges induce nontrivial effects on the electronic band structures. Recently, the blue shift of the peak wavelength in photo-absorption spectra for a DNBDT-monolayer transistor was experimentally observed by increasing an ionic-liquid gate voltage, although the origin of the shift is still under debate. Therefore, we investigate the hole-doping and external electric-field effects on the electronic states of the organic semiconducting monolayer within the framework of the density functional theory. The calculated results show that the photo-absorption energy is increased by hole doping while an external field decreases the photo-absorption energy. We demonstrated that the calculations give useful information to understand the origin of the experimentally observed wavelength shift of photo-absorption spectra.

We present theoretical calculations of the thermoelectric properties of a magnetic semi-conductor CuFeS2. The electrical contributions, namely the Seebeck coefficients, electrical conductances, and electronic thermal conductances, are investigated using first-principles calculation techniques based on density functional theory and the nonequilibrium Green's function formalism. The lattice thermal transport properties are analyzed using the nonequilbirium molecular dynamics simulation method. Using a combination of the calculated electronic contributions and the lattice thermal contribution, the thermoelectric figures of merit are calculated and analyzed in doped configurations for the theoretical prediction of the highest thermoelectic energy conversion efficiency. It is shown that dilute doping enhances the figure of merit by 2.5 times compared to 3% doping which was previously experimentally obtained to give the best thermoelectric performance among samples studied.

The thermoelectric properties of TiN/MgO surface nanostructures have been determined using first-principles calculations based on the nonequilibrium Green’s function (NEGF) method. Through structural modification of the surfaces at the atomistic level, we find that the metallic TiN thin-film layer becomes semiconducting with a small bandgap, which enhances the Seebeck coefficient, while the electrical conductivity remains high at room temperature. Hence, a much larger thermoelectric figure of merit is obtained compared with bulk. These findings indicate the possibility of designing thermoelectric devices with surface nanostructures.

We present an order-$N$ methodology to evaluate mobilities of charge carriers coupled with molecular vibrations using quantum dynamics based on first-principles calculations that can be applied to micron-scale soft materials. As a demonstration, we apply it to several organic semiconductors and show that the calculated intrinsic hole mobilities and their temperature dependences are quantitatively in good agreement with those obtained in experiments. We also clarified which vibrational modes dominate the transport properties. The methodology paves the way for quantitative prediction of the transport properties of various soft materials.

OBJECTIVES: To evaluate the mean concentration of 25-hydroxivitamin D [25(OH) D] and prevalence of hypovitaminosis D in individuals residing in Rio de Janeiro, Brazil. METHODS: The data of 80,000 consecutive individuals who had 25(OH) D measurements performed by electrochemiluminescence between 1/2/2018 and 2/5/2018 were selected. Patients who reported the use of therapies/supplements were excluded. Levels of 25(OH) D ≥20 ng/mL (ages

To achieve high surface flatness of silicon wafer in double-sided polishing (DSP) process, kinematical model of DSP process utilizing accurate friction coefficient between wafer and polishing pad was investigated. On the basis of the proposed analytical model, optimization method of a set of rotation conditions of upper/lower platens and inner/outer gears was developed. Optimizations for two types of DSP processes were performed as case study and those results confirmed that the developed optimization method was effective in obtaining the appropriate rotation conditions for achieving high surface flatness of wafer while decreasing the motor load of platens and gears.

We present a theoretical study of relationships between charge transport properties and disorder in rubrene single crystals. We take into account two different types of disorder, namely, intrinsic dynamical disorder due to intermolecular vibrations and extrinsic static disorder. Then we evaluate the transport properties using our wave-packet dynamical approach which gives us a unified theoretical description from hopping to band transport behavior. We show that the mobilities are completely changed from the intrinsic power-law temperature dependence to the thermally activated behavior by introduction of the extrinsic trap potentials.

We developed and implemented a numerical code called SAKE, which stands for (simulation code for atomistic Kohn-Sham equation). We developed it for first-principle electron transport calculations based on density-functional theory and non-equilibrium Green's function formalism. First, we present the central calculation parts of the formalism of the electronic states and transport properties for open and non-equilibrium systems. We show specific computational techniques, such as the use of a complex contour integration for charge density from the density matrix, which is compared with the calculation method of summing the residues of the Fermi-Dirac distribution, as well as the efficient achievement of the self-consistent procedures. Thereafter, for applications of the present computation code, SAKE, we present first-principle calculation results of three different systems. We first analyze electronic structures of polythiophene molecular wires, compare summation techniques for the density matrix. We show thermoelectric properties of an n-type antiferromagnetic semiconductor CuFeS2 as a second application. The electrical conductance, electrical thermal conductance, and the Seebeck coefficients with carrier doping are examined, and the analytical form of the Seebeck coefficient is briefly described. For the third application, we analyze the electron transport properties of polyaniline molecular wires under structural deformations, i.e. rotations around the transport direction. The thermally averaged current-voltage characteristics are also analyzed. The results show that the current decreases as the temperature increases which are determined based on the competition between the thermal energy and the electronic energy, which increases with the rotation angle.

Prediction of material properties of newly designed molecules is a long-term goal in organic electronics. In general, it is a difficult problem, because the material properties are dominated by the unknown packing structure. We present a practical method to obtain charge transport properties of organic single crystals, without use of experimental single-crystal data. As a demonstration, we employ the promising molecule C10–DNBDT. We succeeded in quantitative evaluation of charge mobility of the single crystal using our quantum wave-packet dynamical simulation method. Here, the single-crystal data is computationally obtained by searching possible packing structures from structural formula of the molecule. We increase accuracy in identifying the actual crystal structure from suggested ones by using not only crystal energy but also similarity between calculated and experimental powder X-ray diffraction patterns. The proposed methodology can be a theoretical design technique for efficiently developing new high-performance organic semiconductors, since it can estimate the charge transport properties at early stage in the process of material development.