Wavefunction matching for solving quantum many-body problems.

Ab initio calculations have an essential role in our fundamental understanding of quantum many-body systems across many subfields, from strongly correlated fermions1-3 to quantum chemistry4-6 and from atomic and molecular systems7-9 to nuclear physics10-14. One of the primary challenges is to perform accurate calculations for systems where the interactions may be complicated and difficult for the chosen computational method to handle. Here we address the problem by introducing an approach called wavefunction matching. Wavefunction matching transforms the interaction between particles so that the wavefunctions up to some finite range match that of an easily computable interaction. This allows for calculations of systems that would otherwise be impossible owing to problems such as Monte Carlo sign cancellations. We apply the method to lattice Monte Carlo simulations15,16 of light nuclei, medium-mass nuclei, neutron matter and nuclear matter. We use high-fidelity chiral effective field theory interactions17,18 and find good agreement with empirical data. These results are accompanied by insights on the nuclear interactions that may help to resolve long-standing challenges in accurately reproducing nuclear binding energies, charge radii and nuclear-matter saturation in ab initio calculations19,20.

Behavioral, Histopathologic, and Molecular Biological Responses of Nanoparticle- and Solution-Based Formulations of Vincristine in Mice.

Clinical use of the chemotherapeutic agent vincristine (VCR) is limited by chemotherapy-induced peripheral neuropathy (CiPN). A new formulation of VCR encapsulated by nanoparticles has been proposed and developed to alleviate CiPN. We hypothesized in nonclinical animals that the nanoparticle drug would be less neurotoxic due to different absorption and distribution properties to the peripheral nerve from the unencapsulated free drug. Here, we assessed whether VCR encapsulation in nanoparticles alleviates CiPN using behavioral gait analysis (CatWalk), histopathologic and molecular biological (RT-qPCR) approaches. Adult male C57BL/6 mice were assigned to 3 groups (empty nanoparticle, nano-VCR, solution-based VCR, each n = 8). After 15 days of dosing, animals were euthanized for tissue collection. It was shown that intraperitoneal administration of nano-VCR (0.15 mg/kg, every other day) and the empty nanoparticle resulted in no changes in gait parameters; whereas, injection of solution-based VCR resulted in decreased run speed and increased step cycle and stance (P < 0.05). There were no differences in incidence and severity of degeneration in the sciatic nerves between the nano-VCR-dosed and solution-based VCR-dosed animals. Likewise, decreased levels of a nervous tissue-enriched microRNA-183 in circulating blood did not show a significant difference between the nano- and solution-based VCR groups (P > 0.05). Empty nanoparticle administration did not cause any behavioral, microRNA, or structural changes. In conclusion, this study suggests that the nano-VCR formulation may alleviate behavioral changes in CiPN, but it does not improve the structural changes of CiPN in peripheral nerve. Nanoparticle properties may need to be optimized to improve biological observations.

Template-Free Synthesis of a Molecular Solomon Link by Two-Component Self-Assembly.

A molecular Solomon link was synthesized in high yield through the template-free, coordination-driven self-assembly of a carbazole-functionalized donor and a tetracene-based dinuclear ruthenium(II) acceptor. The doubly interlocked topology was realized by a strategically chosen ligand which was capable of participating in multiple CH⋅⋅⋅π and π-π interactions, as evidenced from single-crystal X-ray analysis and computational studies. This method is the first example of a two-component self-assembly of a molecular Solomon link using a directional bonding approach. The donor alone was not responsible for the construction of the Solomon link, and was confirmed by its noncatenane self-assemblies obtained with other similar ruthenium(II) acceptors.

Enhanced luminous efficacy in phosphor-converted white vertical light-emitting diodes using low index layer.

We demonstrated improved luminous efficacy for GaN-based vertical light emitting diodes (VLEDs) employing a low index layer composed of silicon dioxide (SiO(2)) on the top surface. Three-dimensional ðnite-difference time-domain simulations for the fabricated VLED chip show that the penetration ratio of the emitted/reflected light into the VLED chip decreased by approximately 20% compared to a normal VLED chip. This result is in good agreement with an empirical study stating that white VLEDs having a SiO(2) layer exhibit an 8.1% higher luminous efficacy than white VLEDs with no layer at an injection current of 350 mA. Photons penetrating into the VLED chip, which become extinct in the VLED chip, are reflected from the SiO(2) layer due to the index contrast between the SiO(2) layer and epoxy resin containing phosphor, with no degradation of the light-extraction efficiency of the VLED chip. As such, this structure can contribute to the enhancement of the luminous efficacy of VLEDs.

An improvement of light extraction efficiency for GaN-based light emitting diodes by selective etched nanorods in periodic microholes.

We have demonstrated the enhancement of a GaN-based light emitting diode (LED) by means of a selective etching technique. A conventional LED structure was periodically etched, to form periodic microholes. It showed an improvement of the light extraction efficiency (LEE) of approximately 15%, compared to that of a conventional LED. Furthermore, nano-sized rods inside the microholes were randomly formed by using a powder mask, resulting in an LEE of 43%. From the result of confocal scanning electroluminescence measurement, the light emission arises mainly from the vicinity of the nanorods in the periodic microholes. Therefore, we found that nanorods randomly distributed in periodic microholes in a LED structure play a significant role in the reduction of total internal reflection, by acting as photon wave-guides and scattering centers. This method would be valuable for the fabrication of high efficiency GaN-based LED, in terms of technical simplification and cost.

High-efficiency GaN-based vertical light-emitting diodes with periodic beveled rod-shaped structures.

The periodic beveled micro-rods (BMRs) were constructed on the emission surface of GaN-based vertical light-emitting diodes (VLEDs) in order to improve the light-extraction efficiency. It was experimentally demonstrated that the light output power of the VLEDs with a periodic BMR (BMR-VLED) were enhanced about 15.6%, compared with that of the VLEDs with randomly textured surface (RT-VLED) at an injection current of 350 mA. This finding indicates that the photons emitted from the active layer were well out-coupled at an n-GaN surface having a periodic BMR structure, resulting in an increase in the probability of escaping from the VLED structure.

Improved photoluminescence efficiency in UV nanopillar light emitting diode structures by recovery of dry etching damage.

In this study, we have fabricated 375-nm-wavelength InGaN/AlInGaN nanopillar light emitting diodes (LED) structures on c-plane sapphire. A uniform and highly vertical nanopillar structure was fabricated using self-organized Ni/SiO2 nano-size mask by dry etching method. To minimize the dry etching damage, the samples were subjected to high temperature annealing with subsequent chemical passivation in KOH solution. Prior to annealing and passivation the UV nanopillar LEDs showed the photoluminescence (PL) efficiency about 2.5 times higher than conventional UV LED structures which is attributed to better light extraction efficiency and possibly some improvement of internal quantum efficiency due to partially relieved strain. Annealing alone further increased the PL efficiency by about 4.5 times compared to the conventional UV LEDs, while KOH passivation led to the overall PL efficiency improvement by more than 7 times. Combined results of Raman spectroscopy and X-ray photoelectron spectroscopy (XPS) suggest that annealing decreases the number of lattice defects and relieves the strain in the surface region of the nanopillars whereas KOH treatment removes the surface oxide from nanopillar surface.

Naringin promotes fat browning mediated by UCP1 activation via the AMPK signaling pathway in 3T3-L1 adipocytes.

Induction of the brown adipocyte-like phenotype in white adipocytes (fat browning) is considered a promising therapeutic strategy to treat obesity. Naringin, a citrus flavonoid, has antioxidant, anti-inflammatory, and anticancer activities. We examined the application of naringin as an anti-obesity compound based on an investigation of its induction of fat browning in 3T3-L1 adipocytes. Naringin did not induce lipid accumulation in differentiated 3T3-L1 adipocytes. Additionally, naringin reduced the expression levels of proliferator-activated receptor gamma (PPARγ) and CCAAT/enhancer-binding protein alpha (C/EBPα) involved in adipogenesis during lipid metabolism and increased the levels of PPARα and adiponectin involved in fatty acid oxidation. The expression levels of fat browning markers uncoupling protein 1 (UCP1; involved in thermogenesis) and PR domain containing 16 (PRDM16) increased. In addition, naringin treatment resulted in the activation of PPARγ coactivator 1-alpha (PGC-1α), a factor related to UCP1 transcription and mitochondrial biogenesis. Moreover, the expression of beige adipocyte-specific genes such as Cd137, Cited1, Tbx1, and Tmem26 was also induced. The small multi-lipid droplets characteristic of beige adipocytes indicated that naringin treatment increased the levels of all lipolysis markers (hormone-sensitive lipase [HSL], adipose triglyceride lipase [ATGL], perilipin [PLIN], and protein kinase A [PKA]). Adenosine monophosphate-activated protein kinase (AMPK) and UCP1 levels increased by treatment with naringin alone; this was possibly mediated by the stimulation of the AMPK signaling pathway. According to mechanistic studies, naringin activated the thermogenic protein UCP1 via the AMPK signaling pathway. In conclusion, naringin induces fat browning and is a promising therapeutic agent for metabolic disorders based on the regulation of lipid metabolism.

The Relationship Between Employees' Daily Customer Injustice and Customer-Directed Sabotage: Cross-Level Moderation Effects of Emotional Stability and Attentiveness.

Customer injustice has received considerable attention in the field of organizational behavior because it generates a variety of negative outcomes. Among possible negative consequences, customer-directed sabotage is the most common reaction, which impacts individuals' well-being and the prosperity of organizations. To minimize such negative consequences, researchers have sought to identify boundary conditions that could potentially attenuate the occurrence of customer-directed sabotage. In this study, we explore potential attenuation effects of emotional stability and attentiveness on the customer injustice-sabotage linkage. The results showed emotional stability and attentiveness moderate the relationship between customer injustice and customer-directed sabotage. Specifically, the representatives with higher (vs. lower) emotional stability or higher (vs. lower) attentiveness are less likely to engage in customer-directed sabotage when they experience customer injustice. Moreover, there is a three-way interaction among daily customer injustice, emotional stability, and attentiveness that predicts daily customer-directed sabotage. Theoretical and practical contributions, limitations, and directions for future development are also discussed.

A unique non-catenane interlocked self-assembled supramolecular architecture and its photophysical properties.

A novel, interlocked, self-assembled (M(2)L(2))(2) molecular architecture was constructed from an arene-Ru acceptor and a 1,4-di(pyridin-4-yl)buta-1,3-diyne donor. Two M(2)L(2) units, with cavities of ~7.21 Å, spontaneously interlock, with one unit encapsulating a twin in a non-catenane fashion. The dimeric host-guest complex thus formed is unique among two-dimensional self-assemblies and is stabilized by π-π interactions between the M(2)L(2) units.

Self-assembled arene-ruthenium-based rectangles for the selective sensing of multi-carboxylate anions.

Novel arene-ruthenium [2+2] metalla-rectangles 4 and 5 have been synthesized by self-assembly using dipyridyl amide ligand 3 and arene-ruthenium acceptors (arene: benzoquinone (1), naphthacenedione (2)) and characterized by NMR spectroscopy and ESI-MS. The solid-state structure of 5 was determined by X-ray diffraction and shows encapsulated diethyl ether molecule in the rectangular cavity of 5. The luminescent 5 was further used for anion sensing with the amidic linkage serving as a hydrogen-bond donor site for anions and the ruthenium moiety serving as a signaling unit. A UV/Vis titration study demonstrated that although 5 interacts very weakly with common monoanions as well as with flexible dicarboxylate anions such as malonate and succinate, it displays significant binding affinity (K>10(3) in MeOH) for rigid multi-carboxylate anions such as oxalate, citrate, and tartrate, exhibiting a 1:1 stoichiometry. It has been suggested that 1:1 bidentate hydrogen bonding assisted by appropriate geometrical complementarity is mainly responsible for the increased affinity of 5 towards such anions. A fluorescence titration study revealed a large fluorescence enhancement of 5 upon binding to multi-carboxylate anions, which can be attributed to the blocking of the photoinduced electron-transfer process from the arene-Ru moiety to the amidic donor in 5 as a result of hydrogen bonding between the donor and the anion.

Fabrication of 380 nm ultra violet light emitting diodes on nano-patterned n-type GaN substrate.

380 nm ultraviolet (UV) light emitting diodes (LEDs) were grown on patterned n-type GaN substrate (PNS) with silicon dioxide (SiO2) nano pattern to improve the light output efficiency. Wet etched self assembled indium tin oxide (ITO) nano clusters serves as dry etching mask for converting the SiO2 layer grown on n-GaN template into SiO2 nano patterns by inductively coupled plasma etching. Three different diameter of ITO such as 200, 250 and 300 nm were used for SiO2 nano pattern fabrication. PNS is obtained by n-GaN regrowth on SiO2 nano patterns and UV LEDs were grown on PNS template by MOCVD. Enhanced light output intensity was observed by employing SiO2 nano patterns on n-GaN. Among different PNS UV LEDs, LED grown on PNS with 300 nm ITO diameter showed enhancement in light output intensity by 2.1 times compared to the reference LED without PNS.

High Quality AlN Layer Grown on Patterned Sapphire Substrates by Hydride Vapor-Phase Epitaxy: A Route for Cost Efficient AlN Templates for Deep Ultraviolet Light Devices.

We report the characteristics of AlN epilayers grown directly on cylindrical-patterned sapphire substrates (CPSS) by hydride vapor-phase epitaxy (HVPE). To evaluate the effect of CPSS, we analyzed the threading dislocation densities (TDDs) of AlN films grown simultaneously on CPSS and flat sapphire substrate (FSS) by transmission electron microscopy (TEM). The corresponding TDD is measured to be 5.69 x 108 cm-2 for the AlN sample grown on the CPSS that is almost an order of magnitude lower than the value of 3.43 × 109 cm-2 on the FSS. The CPSS contributes to reduce the TDs originated from the AlN/sapphire interface via bending the TDs by lateral growth during the coalescence process. In addition, the reduction of direct interface area between AlN and sapphire by CPSS reduce the generation of TDs.

New Self-assembled Supramolecular Bowls as Potent Anticancer Agents for Human Hepatocellular Carcinoma.

We report herein on the design, synthesis and biological activity of Ru-based self-assembled supramolecular bowls as a potent anticancer therapeutic in human hepatocellular cancer. The potent complex induces production of reactive oxygen species (ROS) by higher fatty acid ß-oxidation and down-regulation of glucose transporter-mediated pyruvate dehydrogenase kinase 1 via reduced hypoxia-inducible factor 1α. Also, overexpressed acetyl-CoA activates the tricarboxylic acid cycle and the electron transport system and induces hypergeneration of ROS. Finally, ROS overexpressed through this pathway leads to apoptosis. Furthermore, we demonstrate that the naphthalene derived molecular bowl activates classical apoptosis via crosstalk between the extrinsic and intrinsic signal pathway. Our work into the mechanism of Ru-based self-assembled supramolecular bowls can provide valuable insight into the potential for use as a promising anticancer agent.

Safety evaluation and consideration of 4 Pin Multi-needle for meso-therapy.

This study was conducted according to the method presented in the Republic of Korea Pharmacopoeia 11th Revision, aseptic test method to evaluate the suitability of sterilization for a sterile needle (4 Pin Multi-needle). In this study, four tests were conducted: sterility test, cytotoxicity test, acute toxicity test, skin sensitization test. First, in the aseptic test, the microorganism was not proliferated in the aseptic test of the medium. As a result of the performance test of the medium, it was confirmed that the microorganism developed within 3 days and the fungus was evident within 5 days. Based on this, it was confirmed that the medium was suitable, and as a result of the aseptic test, the development of microorganisms was not observed during the total culture period. Based on these results, tests were conducted which were confirmed to be suitable for aseptic testing because the development of bacteria on the provided samples was not recognized. For cytotoxicity tests ISO10993-5; 2009 (Biological Evaluation of Medical Devices, Part 5: Test for in vitro Cytotoxicity). As a result, the MEM eluate of the test substance caused very slight cytotoxicity to the fibroblasts of the mouse and was judged to be Grade 1 (Slightly cytotoxic) according to the judgment standard of ISO 10993-5. On the other hand, solvent control, negative control and positive control showed the expected results on the test. Acute Toxicity Test Results: It was judged that there was no systemic toxicity change when ICR mice were treated with 50 mL/kg B.W. of the eluate of sterile injectable needle for 72 hours. Skin sensitization test result: The Hartley guinea pig was evaluated as a substance which is evaluated as a substance which does not induce any skin reaction when skin sensitization is applied to the dissected material of the sterile injectable needle and is weak in skin sensitivity. Based on the above tests, we will study the stability and efficacy of more reliable medical devices based on the verification and performance of medical devices.

Extending the multifoci perspective: The role of supervisor justice and moral identity in the relationship between customer justice and customer-directed sabotage.

The multifoci perspective of justice proposes that individuals tend to target their (in)justice reactions toward the perceived source of the mistreatment. Empirical support for target-specific reactions, however, has been mixed. To explore theoretically relevant reasons for these discrepant results and address unanswered questions in the multifoci justice literature, the present research examines how different justice sources might interactively predict target-specific reactions, and whether these effects occur as a function of moral identity. Results from a sample of North American frontline service employees (N = 314, Study 1) showed that among employees with lower levels of moral identity, low supervisor justice exacerbated the association between low customer justice and customer-directed sabotage, whereas this exacerbation effect was not observed among employees with higher levels of moral identity. This 3-way interaction effect was replicated in a sample of South Korean employees (N = 265, Study 2).

A novel in situ hydrophobic ion paring (HIP) formulation strategy for clinical product selection of a nanoparticle drug delivery system.

The present studies were aimed at formulating AZD2811-loaded polylactic acid-polyethylene glycol (PLA-PEG) nanoparticles with adjustable release rates without altering the chemical structures of the polymer or active pharmaceutical ingredient (API). This was accomplished through the use of a hydrophobic ion pairing approach. A series of AZD2811-containing nanoparticles with a variety of hydrophobic counterions including oleic acid, 1-hydroxy-2-naphthoic acid, cholic acid, deoxycholic acid, dioctylsulfosuccinic acid, and pamoic acid is described. The hydrophobicity of AZD2811 was increased through formation of ion pairs with these hydrophobic counterions, producing nanoparticles with exceptionally high drug loading-up to five fold higher encapsulation efficiency and drug loading compared to nanoparticles made without hydrophobic ion pairs. Furthermore, the rate at which the drug was released from the nanoparticles could be controlled by employing counterions with various hydrophobicities and structures, resulting in release half-lives ranging from about 2 to 120h using the same polymer, nanoparticle size, and nanoemulsion process. Process recipe variables affecting drug load and release rate were identified, including pH and molarity of quench buffer. Ion pair formation between AZD2811 and pamoic acid as a model counterion was investigated using solubility enhancement as well as nuclear magnetic resonance spectroscopy to demonstrate solution-state interactions. Further evidence for an ion pairing mechanism of controlled release was provided through the measurement of API and counterion release profiles using high-performance liquid chromatography, which had stoichiometric relationships. Finally, Raman spectra of an AZD2811-pamoate salt compared well with those of the formulated nanoparticles, while single components (AZD2811, pamoic acid) alone did not. A library of AZD2811 batches was created for analytical and preclinical characterization. Dramatically improved preclinical efficacy and tolerability data were generated for the pamoic acid lead formulation, which has been selected for evaluation in a Phase 1 clinical trial (ClinicalTrials.gov Identifier NCT 02579226). This work clearly demonstrates the importance of assessing a wide range of drug release rates during formulation screening as a critical step for new drug product development, and how utilizing hydrophobic ion pairing enabled this promising nanoparticle formulation to proceed into clinical development.

Aurora kinase inhibitor nanoparticles target tumors with favorable therapeutic index in vivo.

Efforts to apply nanotechnology in cancer have focused almost exclusively on the delivery of cytotoxic drugs to improve therapeutic index. There has been little consideration of molecularly targeted agents, in particular kinase inhibitors, which can also present considerable therapeutic index limitations. We describe the development of Accurin polymeric nanoparticles that encapsulate the clinical candidate AZD2811, an Aurora B kinase inhibitor, using an ion pairing approach. Accurins increase biodistribution to tumor sites and provide extended release of encapsulated drug payloads. AZD2811 nanoparticles containing pharmaceutically acceptable organic acids as ion pairing agents displayed continuous drug release for more than 1 week in vitro and a corresponding extended pharmacodynamic reduction of tumor phosphorylated histone H3 levels in vivo for up to 96 hours after a single administration. A specific AZD2811 nanoparticle formulation profile showed accumulation and retention in tumors with minimal impact on bone marrow pathology, and resulted in lower toxicity and increased efficacy in multiple tumor models at half the dose intensity of AZD1152, a water-soluble prodrug of AZD2811. These studies demonstrate that AZD2811 can be formulated in nanoparticles using ion pairing agents to give improved efficacy and tolerability in preclinical models with less frequent dosing. Accurins specifically, and nanotechnology in general, can increase the therapeutic index of molecularly targeted agents, including kinase inhibitors targeting cell cycle and oncogenic signal transduction pathways, which have to date proved toxic in humans.

Anticancer activities of self-assembled molecular bowls containing a phenanthrene-based donor and Ru(II) acceptors.

Nano-sized multinuclear ruthenium complexes have rapidly emerged as promising therapeutic candidates with unique anticancer activities. Here, we describe the coordination-driven self-assembly and anticancer activities of a set of three organometallic tetranuclear Ru(II) molecular bowls. [2+2] Coordination-driven self-assembly of 3, 6-bis(pyridin-3- ylethynyl) phenanthrene (bpep) (1) and one of the three dinuclear arene ruthenium clips, [(η6-p-iPrC6H4Me)2Ru2-(OO\OO)][OTf]2 (OO\OO =2, 5-dioxido-1, 4-benzoquinonato, OTf = triflate) (2), 5, 8-dioxido-1, 4-naphthoquinonato (3), or 6, 11-dioxido-5, 12-naphthacenediona (4), resulted in three molecular bowls 5-7 of general formula [{(η6-p-iPrC6H4Me)2Ru2-(OO\OO)}2(bpep)2][OTf]4. All molecular bowls were obtained as triflate salts in very good yields (>90%) and were fully characterized using multinuclear nuclear magnetic resonance (NMR), electrospray ionization-mass spectrometry (ESI-MS), and elemental analysis. The structure of the representative molecular bowl 5 was confirmed by single-crystal X-ray diffraction analysis. The anticancer activities of molecular bowls 5-7 were determined by 3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide, autophagy, and Western blot analysis. Bowl 6 showed the strongest cytotoxicity in AGS human gastric carcinoma cells and was more cytotoxic than doxorubicin. In addition, autophagic activity and the ratio of apoptotic cell death increased in AGS cells by treatment with bowl 6. Bowl 6 also induced autophagosome formation via upregulation of p62 and promotion of the conversion of LC3-I to LC3-II. Moreover, bowl 6 promoted apoptotic cell death through downregulation of Akt/mTOR activation, followed by increased caspase-3 activity. These results suggest that bowl 6 induces gastric cancer cell death via modulation of autophagy and apoptosis. Bowl 6 is a potent anticancer agent and a potential treatment for human gastric cancer that merits further study.

Coordination-driven self-assembly of an iridium-cornered prismatic cage and encapsulation of three heteroguests in its large cavity.

A hollow iridium-cornered prismatic cage was self-assembled without the assistance of any template. The cage was found to be capable of encapsulating heteroguest's triplet in its perfect sized cavity, producing the first demonstration of quintuple structure by an octahedral metal cornered prismatic cage.