Intermediate Precursor Research Articles

Sonic Hedgehog Effectively Improves Oct4-Mediated Reprogramming of Astrocytes into Neural Stem Cells.

Irreversible neuron loss following spinal cord injury (SCI) usually results in persistent neurological dysfunction. The generation of autologous neural stem cells (NSCs) holds great potential for neural replenishment therapies and drug screening in SCI. Our recent studies demonstrated that mature astrocytes from the spinal cord can directly revert back to a pluripotent state under appropriate signals. However, in previous attempts, the reprogramming of astrocytes into induced NSCs (iNSCs) was unstable, inefficient, and frequently accompanied by generation of intermediate precursors. It remained unknown how to further increase the efficiency of astrocyte reprogramming into iNSCs. Here, we show that mature astrocytes could be directly converted into iNSCs by a single transcription factor, Oct4, and that the iNSCs displayed typical neurosphere morphology, authentic NSC gene expression, self-renewal capacity, and multipotency. Strikingly, Oct4-driven reprogramming of astrocytes into iNSCs was potentiated with continuous sonic hedgehog (Shh) stimulation, as demonstrated by a sped-up reprogramming and increased conversion efficiency. Moreover, the iNSC-derived neurons possessed functionality as neurons. Importantly, crosstalk between Sox2/Shh-targeted downstream signals and phosphatidylinositol 3-kinase/cyclin-dependent kinase 2/Smad ubiquitin regulatory factor 2 (PI3K/Cdk2/Smurf2) signaling is likely involved in the mechanisms underlying this cellular event. The highly efficient reprogramming of astrocytes to generate iNSCs will provide an alternative therapeutic approach for SCI using autologous cells.

Toward Developing a Yeast Cell Factory for the Production of Prenylated Flavonoids.

Prenylated flavonoids possess a wide variety of biological activities, including estrogenic, antioxidant, antimicrobial, and anticancer activities. Hence, they have potential applications in food products, medicines, or supplements with health-promoting activities. However, the low abundance of prenylated flavonoids in nature is limiting their exploitation. Therefore, we investigated the prospect of producing prenylated flavonoids in the yeast Saccharomyces cerevisiae. As a proof of concept, we focused on the production of the potent phytoestrogen 8-prenylnaringenin. Introduction of the flavonoid prenyltransferase SfFPT from Sophora flavescens in naringenin-producing yeast strains resulted in de novo production of 8-prenylnaringenin. We generated several strains with increased production of the intermediate precursor naringenin, which finally resulted in a production of 0.12 mg L–1 (0.35 μM) 8-prenylnaringenin under shake flask conditions. A number of bottlenecks in prenylated flavonoid production were identified and are discussed.

Mo addition for improved electrochromic properties of V2O5 thick films

Transition metal oxides (TMOs) have attracted considerable attention due to their variety of chromogenic properties. Among them, vanadium pentoxide (V2O5) has gained significant interest in respect of multichromism associated with orange, green and blue colors. Herein, we report a simple and easy method for the fabrication of Mo doped V2O5 thick films, leading to improved cyclability. Molybdenum doped vanadium pentoxide powders were synthesized from one single polyol route through the precipitation of an intermediate precursor: molybdenum doped vanadium ethyleneglycolate (Mo doped VEG). The as-synthesized Mo-doped V2O5 exhibits improved electrochromic performance in terms of capacity, cycling stability, and color contrast compared to single-component V2O5 in lithium as well as sodium based electrolyte. The improvement in EC performances lies in films of higher porosity as well as higher diffusion coefficients. To conclude, an electrochromic device combining Mo-V2O5 to WO3.2H2O, via a PMMA-lithium based electrolyte membrane exhibits simultaneously reversible color change from yellow to green for Mo-V2O5 and from blue to yellow white for WO3.2H2O with a cycling stability up to 10 000 cycles.

HDAC1 and HDAC2 independently regulate common and specific intrinsic responses in murine enteroids

Both HDAC1 and HDAC2 are class I deacetylases acting as erasers of lysine-acetyl marks on histones and non-histone proteins. Several histone deacetylase inhibitors, either endogenous to the cell, such as the ketogenic β-hydroxybutyrate metabolite, or exogenous, such as butyrate, a microbial-derived metabolite, regulate HDAC activity. Different combinations of intestinal epithelial cell (IEC)-specific Hdac1 and/or Hdac2 deletion differentially alter mucosal homeostasis in mice. Thus, HDAC1 and HDAC2 could act as sensors and transmitters of environmental signals to the mucosa. In this study, enteroid culture models deleted for Hdac1 or Hdac2 were established to determine IEC-specific function as assessed by global transcriptomic and proteomic approaches. Results show that Hdac1 or Hdac2 deficiency altered differentiation of Paneth and goblet secretory cells, which sustain physical and chemical protection barriers, and increased intermediate secretory cell precursor numbers. Furthermore, IEC Hdac1- and Hdac2-dependent common and specific biological processes were identified, including oxidation-reduction, inflammatory responses, and lipid-related metabolic processes, as well as canonical pathways and upstream regulators related to environment-dependent signaling through steroid receptor pathways, among others. These findings uncover unrecognized regulatory similarities and differences between Hdac1 and Hdac2 in IEC, and demonstrate how HDAC1 and HDAC2 may complement each other to regulate the intrinsic IEC phenotype.

Chemistry and pharmacological diversity of quinoxaline motifs as anticancer agents.

Surpassing heart diseases, cancer is taking the lead as the deadliest disease because of its fast rate of spreading in all parts of the world. Tireless commitment to searching for novel therapeutic medicines is a worthwhile adventure in synthetic chemistry because of the drug resistance predicament and regular outbreak of new diseases due to abnormal cell growth and proliferation. Medicinal chemistry researchers and pharmacists have unveiled quinoxaline templates as precursors of importance and valuable intermediates in drug discovery because they have been established to possess diverse pharmacological potentials. Hence, this review highlights the current versatile routes to accessing functionalized quinoxaline motifs and harnessing their documented therapeutic potentials for anticancer drug development.

Biotransformation of lauric acid into 1,12-dodecanedioic acid using CYP52A17 expressed in Saccharomyces cerevisiae and its application in refining coconut factory wastewater

1,12-Dodecanedioic acid (DDA), a primary compound and an intermediate precursor for various chemical products, is normally produced by chemical synthesis, which presents potential disadvantages. Instead, the biosynthesis of 1,12-DDA by recombinant (r) microorganisms may offer a viable production route. Cytochrome P450 (CYP) can terminally oxidize fatty acids to ω-hydroxy-fatty acids and further to dicarboxylic acids (ω-oxidation). The wild type (r) CYP52A17LL and its engineered L261S/L490S form, in which the two leucine residues were changed into serine (rCYP52A17SS), were expressed in Pichia pastoris and a strain of Saccharomyces cerevisiae coexpressing the yeast NADPH cytochrome P450 reductase gene. Both organisms produced 12-hydroxydodecanoic acid (HDDA) and 1,12-DDA from lauric acid. In vitro, microsomes containing rCYP52A17SS extracted from the S. cerevisiae strain BY(2R)/pYeDP60-CYP52A17SS were able to convert lauric acid to 12-HDDA quite efficiently. Biotransformation of lauric acid using S. cerevisiae BY(2R)/pYeDP60-CYP52A17SS in culture gave the highest level of 12-HDDA (45.8 μM) at 24 h, which was oxidized to yield 20.8 μM of 1,12-DDA at 72 h. The recombinant S. cerevisiae BY(2R)/pYeDP60-CYP52A17SS, which was initially cultured in YPGE, produced the highest yield of 1,12-DDA from coconut milk wastewater at 24 h. Hence, our designed S. cerevisiae strain BY(2R)/pYeDP60-CYP52A17SS can potentially produce 1,12-DDA for industrial applications.

Leukocytes from obese individuals exhibit an impaired SPM signature.

Specialized proresolving mediators (SPMs) biosynthesized from docosahexaenoic acids (DHAs) including resolvins (Rvs), protectins, and maresins are potent endogenous autacoids that actively resolve inflammation, protect organs, and stimulate tissue regeneration. Our hypothesis was that failure of resolution programs may lead to unremitting inflammation in obesity, contributing to the development of metabolic comorbidities in this condition. Obese individuals with persistent low-grade systemic inflammation showed reduced leukocyte production of the DHA-derived monohydroxy fatty acid 17-hydroxy-DHA (HDHA) and unbalanced formation of SPMs (in particular D-series Rvs) accompanied by enhanced production of proinflammatory lipid mediators such as leukotriene B4. Mechanistic studies attributed this impairment to reduced 15-lipoxygenase (LOX) activity rather than altered DHA cellular uptake. Moreover, leukocytes from obese individuals exhibited decreased 5-LOX levels and reduced 5-LOX Ser271 phosphorylation and distinct intracellular 5-LOX redistribution. However, 15-LOX appears to be the most critical factor for the deficient production of SPMs by obese leukocytes because the formation of D-series Rvs was completely rescued by incubation with the intermediate precursor 17-HDHA. These data provide proof of concept that administration of intermediate precursors of SPM biosynthesis (e.g., 17-HDHA) could be more efficient in overriding impaired formation of these proresolving lipid mediators in conditions characterized by dysfunctional LOX activity, such as obesity.-López-Vicario, C., Titos, E., Walker, M. E., Alcaraz-Quiles, J., Casulleras, M., Durán-Güell, M., Flores-Costa, R., Pérez-Romero, N., Forné, M., Dalli, J., Clària, J. Leukocytes from obese individuals exhibit an impaired SPM signature.

One-Pot Synthesis of Hypervalent Diaryl(iodo)bismuthanes from o-Carbonyl Iodoarenes by Zincation

Diaryl(iodo)bismuthanes possessing a hypervalent C=O•••Bi–I bond were conveniently synthesized in a one-pot reaction by using arylzinc reagents generated from o-carbonyl iodobenzenes and zinc powder under ultrasonication. This method is superior to the conventional organolithium and Grignard methods because it has a wide functional group tolerance, requires no protecting group manipulations, and proceeds under mild reaction conditions that do not need low temperature control. Furthermore, no intermediate triarylbismuthane precursor for the hypervalent iodobismuthane is necessary.

Operandodual beam FTIR spectroscopy unravels the promotional effect of Zn on HZSM-5 in iso-butane aromatization

Experimental and theoretical results showed that there are special interactions between olefins (as intermediate precursors) and the Zn modified HZSM-5 zeolites, which were absent in the parent HZSM-5.

The ETS1 Transcription Factor Is Implicated in Human and Murine Intermediate NK Cell Development Stages

Introduction: While key regulators of early NK cell development and differentiation have been identified, few studies have looked at transcription factor (TF) dynamics and regulatory interactions during subsequent stages of NK cell maturation. Epigenetic landscapes are highly dynamic during cellular differentiation, with TFs playing an important role in the establishment and activation of specific DNA elements, such as enhancers, and subsequent programming of gene expression. ETS1 is a TF that is expressed in adult immune tissues and is critical for the development of lymphoid cells. A role for ETS1 has been described in early NK cell development by activating core transcriptional regulators such as T-BET and ID2. However, despite its continual expression in subsequent stages of NK maturation, the role of ETS1 in NK maturation is not well characterized.Methods and Results: We used FACS to isolate purified human NK cells at various maturation stages as established previously (Freud et. al. Cell Reports, 2016, 16:379-91), ranging from intermediate precursors (Stage 3) through to fully developed and mature peripheral NK cells (Stage 6). Epigenetic programming of cells during lineage maturation allows us to identify critical TFs that are active at each stage of development. We employed Illumina EPIC/850K methylation arrays and RNA sequencing to interrogate epigenetic changes at regulatory elements and TF dynamics at multiple stages along the NK developmental axis. Analysis of TF recognition motifs within hypomethylated regions revealed strong enrichment of specific motif sequences implicating T-box (T-BET and Eomes), along with RUNX and ETS TF families in specific programming of epigenetic patterns during NK development. In studying the expression of TFs that potentially bind these motifs, ETS1 exhibited the highest and most consistent expression throughout NK development. Interestingly, despite consistently high expression, ETS motifs were continually programmed throughout NK maturation, including a significant degree of modification between tonsillar Stages 4A to 4B, where NK cells acquire the ability to produce IFN-γ and significantly gain cytotoxic capability and functional maturity. Among the genes that are upregulated at this stage is the NK-cell-specific gene, NKp46.The progressive hypomethylation of regulatory regions enriched in ETS motifs led us to believe that ETS1 has a continuous role in full NK cell maturation. To test our hypothesis, we developed a novel genetically engineered mouse line with a NK cell intermediate stage-specific conditional deletion of Ets1 mediated by NKp46-driven Cre expression, NKp46-Cre-Ets1fl/fl (NKp46-Ets1fl/fl). This allowed us to study the role of ETS1 in the transition between immature and mature NK cell stages in vivo. Using a comprehensive NK cell development panel for multi-color flow cytometry, we found a drastic reduction of total NK cells in NKp46-Ets1fl/fl mice (n=7) compared to the Ets1fl/fl (n=7) and the NKp46-Cre (n=7) controls in bone marrow (3.2x104 ± 5.9x103, 2.9x105 ± 5.7x104, 2.6x105 ± 8.0x104 total NK cells respectively; p= 0.0007), spleen (3.1x104 ± 7.2x103, 1.2x106 ± 2.4x105, 1.5x106 ± 7.7x105 total NK cells respectively; p= 0.0091) and blood (21 ± 6, 385 ± 35, 185 ± 35 NK cells/uL whole blood respectively; p= 0.0001). Supporting our hypothesis, we indeed observed that while CD11b-/CD27+/- immature NK cell populations in our model are unaltered, the loss of ETS1 is associated with a decrease in CD11b+/CD27+/- mature NK cell populations.Conclusions: Our findings demonstrate that in addition to its role in early NK establishment, persistent ETS1 expression is important in intermediate differentiation stages in both human and murine NK cell development. This constitutes a significant step forward in understanding the role of ETS1 as a master transcriptional regulator in the entire NK cell developmental axis. Current studies are ongoing to dissect the mechanism by which ETS1 affects NK cell development and function in the NKp46-Ets1fl/fl mice.(*EH and JW are recipients of Pelotonia Graduate and Undergraduate student fellowships respectively and contributed equally to this work. This work was partly supported by OCRA, NIH R01 CA159296, NIH R01 CA208353, P01CA95426, R35 CA197734 and OSUCCC Leukemia Tissue Bank and Genetically Engineered Mouse Modeling Core supported by P30CA016058) DisclosuresNo relevant conflicts of interest to declare.

Systemic Inflammation Impairs Proliferation of Hippocampal Type 2 Intermediate Precursor Cells.

Neurogenesis is a plastic event modulated by external cues. Systemic inflammation decreases neurogenesis in the dentate gyrus (DG) in part through the proliferative restrain of neural precursor cells (NPCs). To evaluate if inflammation affects the cell cycle progression of particular populations of NPCs, we treated young-adult mice with a single i.p. injection of saline or 1mg/kg LPS. After 7days, we analysed proliferation of new BrdU+/DCX+ cells through immunohistochemistry. We extracted the hippocampus and performed a neurosphere assay and a flow cytometric analysis to evaluate proliferation and to identify the phase of the cell cycle in specific populations of DG-derived NPCs. We show that the number of BrdU+/DCX+ cells diminishes in the LPS-treated group and that the number of primary neurospheres derived from LPS-injected animals is significantly reduced compared to the saline-injected group. Flow cytometry revealed that inflammation does not affect the total number of Type 1 BLBP+/TBR2- cells, while the total number of Type 2 intermediate precursor cells (IPCs) (TBR2+) from the LPS-treated group was increased. Cell cycle analysis shows a decrease in the total rate of NPCs in phases S, G2 and M in the LPS-treated group. The percentage of Type 1 BLBP+/TBR2- cells in each cell cycle phase was not different between groups, while there was a fewer number of Type 2 TBR2+ cells in S/G2/M phase. These results show that inflammation alters the appropriate cell cycle progression of Type 2 IPCs, which may contribute to the decrease in the birth rate of DG neurons.

Polyamine Metabolism and Gene Methylation in Conjunction with One-Carbon Metabolism.

Recent investigations have revealed that changes in DNA methylation status play an important role in aging-associated pathologies and lifespan. The methylation of DNA is regulated by DNA methyltransferases (DNMT1, DNMT3a, and DNMT3b) in the presence of S-adenosylmethionine (SAM), which serves as a methyl group donor. Increased availability of SAM enhances DNMT activity, while its metabolites, S-adenosyl-l-homocysteine (SAH) and decarboxylated S-adenosylmethionine (dcSAM), act to inhibit DNMT activity. SAH, which is converted from SAM by adding a methyl group to cytosine residues in DNA, is an intermediate precursor of homocysteine. dcSAM, converted from SAM by the enzymatic activity of adenosylmethionine decarboxylase, provides an aminopropyl group to synthesize the polyamines spermine and spermidine. Increased homocysteine levels are a significant risk factor for the development of a wide range of conditions, including cardiovascular diseases. However, successful homocysteine-lowering treatment by vitamins (B6, B12, and folate) failed to improve these conditions. Long-term increased polyamine intake elevated blood spermine levels and inhibited aging-associated pathologies in mice and humans. Spermine reversed changes (increased dcSAM, decreased DNMT activity, aberrant DNA methylation, and proinflammatory status) induced by the inhibition of ornithine decarboxylase. The relation between polyamine metabolism, one-carbon metabolism, DNA methylation, and the biological mechanism of spermine-induced lifespan extension is discussed.

Nodular monazite from placers in the Kular Ridge (Arctic Siberia, Russia): Composition and age

Nodular monazite occurs in metamorphic rocks worldwide and has zonal REE patterns. This paper focuses on the composition of nodular monazite hosted by Permian black shales of the Kular Ridge in the Kular-Nera terrane. This monazite variety (called kularite in the Russian literature) reaches commercial amounts in placers of the area. The contents of Ce, Nd, and La in the analyzed monazite nodules show correlations at Ce/Nd = 14.39La + 0.0919 (in apfu) and Ce/Nd = 0.2318La + 0.1135 (in wt.%) and vary regularly from core to rim. All monazite compositions fall on this trend, but specific grains may plot in its different parts. Thermodynamic calculations indicate that monazite forms via an intermediate precursor (LnPO4·2H2O). The Ce:La:Nd changes in different grains record Eh-pH variations during nucleation and a gradual temperature increase during subsequent growth. The Ce:La:Nd ratio changes partly in grain rims as a result of oxidative dissolution. Judging by the tectonic setting, REE came to the Kular-Nera rocks from the weathered Tomtor Nb-REE deposit, being transported by the Paleo-Khatanga River with monazite nanoparticles bound to the surface of clay minerals.

Influence of different hydrocarbons on the height of MWCNT carpets: Role of catalyst and hybridization state of the carbon precursor

The length of multi-walled carbon nanotubes (MWCNT) has a particular relevance for a wide range of application. To that end, in an aerosol assisted chemical vapour deposition process MWCNT carpets with different heights were synthesized on an oxidized silicon substrate by using ferrocene as Fe-catalyst precursor and some hydrocarbons with different hybridization state. By variation of the synthesis temperature from 600 °C up to 900 °C, for every used hydrocarbon different carpet heights were measured depending on the temperature. Cyclohexane generated the highest MWCNT carpets and for all carbon precursor the maximum carpet height was measured at 850 °C. To elucidate this, the thermal decomposition of the used hydrocarbons was discussed and the corresponding main decomposition products methane, ethene and benzene were identified. Subsequently, these substances were directly used in a second chemical vapour deposition equipment to simulate the growth mechanism by the intermediate carbon precursors. It was found, that with comparable content of carbon in the gas phase, ethene is much higher efficient for growing high MWCNT carpets than methane. Moreover, benzene was figured out to be also an adequate carbon precursor under specific gas phase conditions, explaining the carpet heights when using toluene and xylene.

Layered Inorganic/Organic Hybrid (CdSe) n·Monoamine Nanobelts: Controllable Solvothermal Synthesis, Multiple Stage Amine De-Intercalation Transformation, and Two-Dimensional Exciton Quantum Confinement Effect.

CdSe nanocrystals, including quantum dots and quantum rods, are a research hotspot in nanomaterials. Recently, it has been found that two-dimensional CdSe semiconductor nanobelts show a unique quantum confinement effect owing to their homogeneous nanoscale thickness. In this study, a series of (CdSe) n·monoamine ( n = 1, 2, and 4, monoamine = butylamine, hexylamine, and octylamine) layered inorganic/organic hybrid nanobelts was synthesized by the solvothermal method. These hybrids have a lamellar structure with a few inorganic [CdSe] layers and monoamine layers alternatively stacked along the c axis of their crystallites, which exhibit the typical preferred orientation for layered crystallites and isomorphous [CdSe] layers according to their X-ray diffraction patterns. The [CdSe] layer is a contracted (110) superlattice cell of wurtzite (WZ)-type CdSe with unit cell parameter relations of a ≈ √3 aWZ and b ≈ cWZ, and a lamellar nanobelt morphology with the [010] growth direction. These ordered hybrids exhibit prominent split exciton absorption peaks and sharp band edge luminescence owing to the homogeneous thickness of the [CdSe] layers within the hybrids, all of which are comparable with reported WZ-type CdSe colloidal nanosheets and exhibit a prominent two-dimensional exciton quantum confinement effect. The solvothermal reaction was systematically investigated. The multiple stage amine de-intercalation topotactic process was revealed for the WZ-type CdSe nanobelts with the (CdSe) n·monoamine ( n = 1, 2, and 4) hybrids as the intermediate phases. The solvothermal synthesis method (70-150 °C) is facile and milder than the traditional hot injection method (>200 °C). Therefore, these hybrids can be considered to be intermediate phases or precursors of WZ-type CdSe nanosheets with a topotactic intralayer [CdSe] structure and also a type of multiple quantum well with extremely thin [CdSe] layers orderly stacked among the monoamine insulating blocking layers.

Palladium(0)-catalyzed rearrangement of allyl enol ethers to form chiral quaternary carbon centers via asymmetric allylic alkylation

Herein we report the first palladium(0)-catalyzed asymmetric allylic alkylation (AAA) of allyl enol ether via π-allylpalladium intermediate using Trost chiral diphosphine. This unprecedented reaction produced very rare α-aryl quaternary aldehydes with multi-functional groups. The main novelty in the chemistry demonstrates that enol ethers can be used as precursors for π-allylpalladium intermediates, an observation that is certainly rare and to the best of our knowledge, perhaps without prior precedent. Chiral ligand (R,R)-L3 was found to be optimal in this Pd-AAA reaction and provided good to excellent yield (80–95%) and enantioselectivity (70–90%) with a range of analogs.

Nonisothermal crystallization kinetics and stability of leucite and kalsilite from K2O‐Al2O3‐SiO2 glasses

AbstractThe crystallization mechanisms and elemental stability of leucite and kalsilite formed from K2O‐Al2O3‐SiO2 glasses were investigated by X‐ray powder diffraction (XRD), X‐ray fluorescence (XRF), Raman spectroscopy and differential scanning calorimetry (DSC). Glass samples with compositions along the leucite‐kalsilite tie‐line were produced by melt processing and were then heat‐treated at 850, 950, and 1250°C for times ranging from 5 minutes to 1000 hours. Kalsilite is an unstable phase that behaves as an intermediate precursor to leucite. Crystalline materials in which kalsilite is the major phase lose potassium upon prolonged heat treatment (1000 hours at 1250°C), in contrast to those with leucite, in which little or no compositional alteration is detected. The formation of leucite from stoichiometric kalsilite is accompanied by the formation of potassium‐doped alumina. The activation energies for leucite and kalsilite crystallization, determined via application of the Kissinger equation to thermal analysis data, were 579 and 548 kJ/mol, respectively. Finally, production of pure leucite can be achieved with more favorable crystallization kinetics when starting with off‐stoichiometric compositions.

Electrochemical Evaluation of the Number of Au Atoms in Polymeric Gold Thiolates by Single Particle Collisions.

Polymeric gold thiolates, [Au(I)SR] n, are common synthetic intermediate precursors of gold nanoclusters and larger nanoparticles. The size and dispersity of the precursors strongly influence the properties of the synthesis products. Evaluating the size of the precursors is not straightforward because they are irregularly shaped (nonspherical) and hard to isolate from solution. Herein, we propose an effective method for determining the number of Au atoms in polymeric thiolate particles from current transients resulting from single precursor collisions, where individual [Au(I)SR] n species are electrochemically reduced at the collector ultramicroelectrode. The developed approach can lead to a better control over the mean size and dispersity of colloidal metal nanoclusters and nanoparticles.

A self-assembled covalent nanoglue

Nano-glues rely on surface chemistry to intimately bond two surfaces together. The bond can be removable, which means it has to weaken, usually with temperature, or it can be a permanent bond, valued for strength, with a covalent bond yielding the highest strength. A practical covalent nanoglue based upon self-assembled monolayers (SAM) with amine and carboxyl termination is demonstrated, and applicable to any surface that bonds these SAM layers. For bonding flat or deformable layers, the SAM layers on each surface bond directly to each other with a peptide or nylon-like bond. For a removable bond or longer covalent structure, nylon chains are grown between the layers to bridge the gap for non-flat and non-flexible substrates. Bond strength and reliability are measured for several preparation schemes for the intermediate layer. A crystallization process is developed to pre-align the intermediate layer precursors and drive off the solvent to improve bond reliability and insure covalent bonding from wafer to wafer (W2W). Both covalent and removable bonds are created. Temperature dependence of the removable bond strength is measured, while the covalent bonds are stronger than our measurement process. The nanoglue does not bond until activated by (modest) heating, so alignment is enabled, and it is directly compatible with a wafer level fluid-self-alignment (FSA) process described elsewhere.

Crystal nucleation and metastable bcc phase in charged colloids: A molecular dynamics study.

The dynamic process of homogenous nucleation in charged colloids is investigated by brute-force molecular dynamics simulation. To check if the liquid-solid transition will pass through metastable bcc, simulations are performed at the state points that definitely lie in the phase region of thermodynamically stable fcc. The simulation results confirm that, in all of these cases, the preordered precursors, acting as the seeds of nucleation, always have predominant bcc symmetry consistent with Ostwald's step rule and the Alexander-McTague mechanism. However, the polymorph selection is not straightforward because the crystal structures formed are not often determined by the symmetry of intermediate precursors but have different characters under different state points. The region of the state point where bcc crystal structures of large enough size are formed during crystallization is narrow, which gives a reasonable explanation as to why the metastable bcc phase in charged colloidal suspensions is rarely detected in macroscopic experiments.