Blocks For Assembly Research Articles

Structure of the SCAN Domain of Human Paternally Expressed Gene 3 Protein

Human paternally expressed gene 3 protein (PEG3) is a large multi-domain entity with diverse biological functions, including acting as a transcription factor. PEG3 contains twelve Cys2-His2 type zinc finger domains, extended regions of predicted disorder and at the N-terminus a SCAN domain. PEG3 has been identified as partner of the E3 ubiquitin-protein ligase Siah1, an association we sought to investigate. An efficient bacterial recombinant expression system of the human PEG3-SCAN domain was prepared and crystals appeared spontaneously when the protein was being concentrated after purification. The structure was determined at 1.95 Å resolution and reveals a polypeptide fold of five helices in an extended configuration. An extensive dimerization interface, using almost a quarter of the solvent accessible surface, and key salt bridge interactions explain the stability of the dimer. Comparison with other SCAN domains reveals a high degree of conservation involving residues that contribute to the dimer interface. The PEG3-SCAN domain appears to constitute an assembly block, enabling PEG3 homo- or heterodimerization to control gene expression in a combinatorial fashion.

Millimeter‐Sized Neural Building Blocks for 3D Heterogeneous Neural Network Assembly

A millimeter-sized neural building block (NBB) shows high versatility to form a 3D heterogeneous neural component. A millimeter-sized 3D neural network between heterogeneous neural tissues is established, and an efficient technique is then developed to observe the spatiotemporal metrological changes of single neuron in the NBB. This technique allows the visualization of axonal extension, dendritic branching, and morphological changes of presynaptic components and synapses in real time.

Assembly block location and sequencing for flat transporters in a planar storage yard of shipyards

Assembly block location and sequencing are two important and related problems for scheduling a flat transporter to perform block storage and transport within a planar storage yard in shipyards. They affect not only the transport efficiency of storage yards but also the productivity and coordination of related workshops. This paper addresses the block location and sequencing at the same time with the purpose of reducing unproductive moves. A heuristic approach is proposed based on a sequencing strategy, a location selecting procedure for the incoming blocks and a policy for relocating blocks. A tabu search algorithm is proposed to improve the solution. Numerical experiments are conducted to validate the effectiveness and efficiency of the proposed approach.

2D Oxide Nanosheets: Controlled Assembly and Applications

Due to the excitements caused by graphene, other 2D materials have increasingly attracted fundamental research interest as they could open up unprecedented physical properties that cannot be attained in graphene. Here, we present the progress made in properties of 2D oxide nanosheets, highlighting emerging functionalities in electronic applications. Oxide nanosheets are exceptionally rich in both structural diversity and electronic properties, with potential application in areas ranging from electronics to spinelectronics. We utilized oxide nanosheets as a building block in the bottom-up assembly, and successfully developed various functional nanodevices such as nanocapacitors, nanosheet FET, spinelectronic devices, and artificial ferroelectrics.

A GRASP approach to transporter scheduling for ship assembly block operations management

In this paper, we address the transporter scheduling problem of ship assembly block operations management, which can be transformed into parallel machine scheduling with sequence-dependent setup times and precedence constraints. The objective is to maximise the workload balance among transporters under the time constraint that all assembly blocks should be transported in the predetermined period. We develop the GRASP algorithm for transporter scheduling, because parallel machine scheduling with sequence-dependent setup times and precedence constraints is an NP-hard problem. Through simulation experiments, we analyse some aspects of the developed GRASP algorithm, and compare the developed GRASP algorithm with other heuristics for large-scale instances and the optimal solution approach for small-sized instances. The comparison experiments show that the developed GRASP algorithm outperforms other heuristics and is a promising heuristic for transporter scheduling.

Research and Application of Location Assignment and Routing Strategies in Block Storage Yard of Shipbuilding

In shipbuilding, the storage yard is used to store assembly blocks of ships. It is an essential part of the shipbuilding system.The storage yard management contains:determining the exact storage locations for the arriving blocks, and determining the storing or retrieving route for each block. Aheuristic approach was proposedto maximize the space utilization and minimize the obstructive. Based on the approach, a storage yard management systemwas built.The system is used by the planners and got positive effect.

Intestine-Specific Mttp Deletion Decreases Mortality and Prevents Sepsis-Induced Intestinal Injury in a Murine Model of Pseudomonas aeruginosa Pneumonia

BackgroundThe small intestine plays a crucial role in the pathophysiology of sepsis and has been referred to as the “motor” of the systemic inflammatory response. One proposed mechanism is that toxic gut-derived lipid factors, transported in mesenteric lymph, induce systemic injury and distant organ failure. However, the pathways involved are yet to be defined and the role of intestinal chylomicron assembly and secretion in transporting these lipid factors is unknown. Here we studied the outcome of sepsis in mice with conditional, intestine-specific deletion of microsomal triglyceride transfer protein (Mttp-IKO), which exhibit a block in chylomicron assembly together with lipid malabsorption.Methodology/Principal Findings Mttp-IKO mice and controls underwent intratracheal injection with either Pseudomonas aeruginosa or sterile saline. Mttp-IKO mice exhibited decreased seven-day mortality, with 0/20 (0%) dying compared to 5/17 (29%) control mice (p<0.05). This survival advantage in Mttp-IKO mice, however, was not associated with improvements in pulmonary bacterial clearance or neutrophil infiltration. Rather, Mttp-IKO mice exhibited protection against sepsis-associated decreases in villus length and intestinal proliferation and were also protected against increased intestinal apoptosis, both central features in control septic mice. Serum IL-6 levels, a major predictor of mortality in human and mouse models of sepsis, were elevated 8-fold in septic control mice but remained unaltered in septic Mttp-IKO mice. Serum high density lipoprotein (HDL) levels were reduced in septic control mice but were increased in septic Mttp-IKO mice. The decreased levels of HDL were associated with decreased hepatic expression of apolipoprotein A1 in septic control mice.Conclusions/SignificanceThese studies suggest that strategies directed at blocking intestinal chylomicron secretion may attenuate the progression and improve the outcome of sepsis through effects mediated by metabolic and physiological adaptations in both intestinal and hepatic lipid flux.

The Endosomal Sorting Complex ESCRT-II Mediates the Assembly and Architecture of ESCRT-III Helices

The endosomal sorting complexes required for transport (ESCRTs) constitute hetero-oligomeric machines that mediate topologically similar membrane-sculpting processes, including cytokinesis, retroviral egress, and multivesicular body (MVB) biogenesis. Although ESCRT-III drives membrane remodeling that creates MVBs, its structure and the mechanism of vesicle formation are unclear. Using electron microscopy, we visualize an ESCRT-II:ESCRT-III supercomplex and propose how it mediates vesicle formation. We define conformational changes that activate ESCRT-III subunit Snf7 and show that it assembles into spiraling ~9 nm protofilaments on lipid monolayers. A high-content flow cytometry assay further demonstrates that mutations halting ESCRT-III assembly block ESCRT function. Strikingly, the addition of Vps24 and Vps2 transforms flat Snf7 spirals into membrane-sculpting helices. Finally, we show that ESCRT-II and ESCRT-III coassemble into ~65 nm diameter rings indicative of a cargo-sequestering supercomplex. We propose that ESCRT-III has distinct architectural stages that are modulated by ESCRT-II to mediate cargo capture and vesicle formation by ordered assembly.

Room-Temperature Fabrication for Functional Oxide Nanofilms Using Oxide Nanosheets

Oxide nanosheets, which possess atomic or molecular thickness and infinite planar lengths, have increasingly attracted fundamental research interest because of their potential to be used as conductors, semiconductors, insulators, and even ferromagnets, depending on their chemical composition and how their atoms are arranged. An attractive aspect of oxide nanosheets is that nanosheets can be organized into various nanoarchitectures by applying solution-based synthetic techniques. It is even possible to tailor superlattice assemblies by tuning the number of nanosheets and their stacking sequences. Sophisticated functionalities or nanodevices can be designed through the selection of nanosheets and combining materials, and precise control over their arrangement at the molecular scale. We utilized oxide nanosheets as a building block in the bottom-up assembly, and successfully developed various functional nanofilms.

Metabolic control analysis of developing oilseed rape (Brassica napus cv Westar) embryos shows that lipid assembly exerts significant control over oil accumulation

Metabolic control analysis allows the study of metabolic regulation. We applied both single- and double-manipulation top-down control analysis to examine the control of lipid accumulation in developing oilseed rape (Brassica napus) embryos. The biosynthetic pathway was conceptually divided into two blocks of reactions (fatty acid biosynthesis (Block A), lipid assembly (Block B)) connected by a single system intermediate, the acyl-coenzyme A (acyl-CoA) pool. Single manipulation used exogenous oleate. Triclosan was used to inhibit specifically Block A, whereas diazepam selectively manipulated flux through Block B. Exogenous oleate inhibited the radiolabelling of fatty acids from [1-(14)C]acetate, but stimulated that from [U-14C]glycerol into acyl lipids. The calculation of group flux control coefficients showed that c. 70% of the metabolic control was in the lipid assembly block of reactions. Monte Carlo simulations gave an estimation of the error of the resulting group flux control coefficients as 0.27±0.06 for Block A and 0.73±0.06 for Block B. The two methods of control analysis gave very similar results and showed that Block B reactions were more important under our conditions. This contrasts notably with data from oil palm or olive fruit cultures and is important for efforts to increase oilseed rape lipid yields.

Immunogold TEM of otoconin 90 and otolin – relevance to mineralization of otoconia, and pathogenesis of benign positional vertigo

Implementation of the deep-etch technique enabled unprecedented definition of substructural elements of otoconia, including the fibrillar meshwork of the inner core with its globular attachments. Subsequently the effects of the principal soluble otoconial protein, otoconin 90, upon calcite crystal growth in vitro were determined, including an increased rate of nucleation, inhibition of growth kinetics and significant morphologic changes. The logical next step, ultrastructural localization of otoconin 90, by means of immunogold TEM in young mature mice, demonstrated a high density of gold particles in the inner core in spite of a relatively low level of mineralization. Here gold particles are typically arranged in oval patterns implying that otoconin 90 is attached to a scaffold consisting of the hexagonal fibrillar meshwork, characteristic of otolin. The level of mineralization is much higher in the outer cortex where mineralized fiber bundles are arranged parallel to the surface. Following decalcification, gold particles, as well as matrix fibrils, presumed to consist of a linear structural phenotype of otolin, are aligned in identical direction, suggesting that they serve as scaffold to guide mineralization mediated by otoconin 90. In the faceted tips, the level of mineralization is highest, even though the density of gold particles is relatively low, conceivably due to the displacement by the dense mineral phase. TEM shows that individual crystallites assemble into iso-oriented columns. Columns are arranged in parallel lamellae which convert into mineralized blocks for hierarchical assembly into the complex otoconial mosaic.Another set of experiments based on immunogold TEM in young mice demonstrates that the fibrils interconnecting otoconia consist of the short chain collagen otolin. By two years of age the superficial layer of mouse otoconia (corresponding to mid-life human) has become demineralized resulting in weakening or loss of anchoring of the fibrils interconnecting otoconia. Consequently, otoconia detached from each other may be released into the endolymphatic space by minor mechanical disturbances. In humans, benign positional vertigo (BPV) is believed to result from translocation of otoconia from the endolymphatic space into the semi-circular canals rendering their receptors susceptible to stimulation by gravity causing severe attacks of vertigo. The combinations of these observations in humans, together with the presented animal experiments, provide a tentative pathogenetic basis of the early stage of BPV.

Visible-Light-Absorbing Polyoxometalates as Building Blocks for All-Inorganic Photosynthetic Assemblies

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Synthesis and phosphonate binding of guanidine-functionalized fluorinated amphiphiles

We report herein convenient procedures for the use of highly fluorinated α,ω-diols (e.g. 1) as building blocks for the rapid assembly of amphiphilic materials containing a fluorous phase region. We describe expedient conversion of the parent diols to both symmetrically and asymmetrically substituted amphiphiles via the installation of an intermediate trifluoromethanesulfonyl ester. These sulfonate esters are versatile and easily manipulated intermediates, which can be readily converted to a variety of nitrogen, halogen, and carbon groups. Moreover, we show that for guanidine-terminated fluorous amphiphiles, these molecules can bind phosphonic acid groups in aqueous media. Thus, these materials offer a new strategy for decorating phosphorylated biomolecules with fluorine-rich coatings.

Self-Organizing Tissue-Engineered Constructs in Collagen Hydrogels

A novel self-organizing behavior of cellularized gels composed of collagen type 1 that may have utility for tissue engineering is described. Depending on the starting geometry of the tissue culture well, toroidal rings of cells or hollow spheroids were prompted to form autonomously when cells were seeded onto the top of gels and the gels released from attachment to the culture well 12 to 24 h after seeding. Cells within toroids assumed distinct patterns of alignment not seen in control gels in which cells had been mixed in. In control gels, cells formed complex three-dimensional arrangements and assumed relatively higher levels of heterogeneity in expression of the fibronectin splice variant ED-A--a marker of epithelial mesenchymal transformation. The tissue-like constructs resulting from this novel self-organizing behavior may have uses in wound healing and regenerative medicine, as well as building blocks for the iterative assembly of synthetic biological structures.

Spectroscopy of Free-Base N-Confused Tetraphenylporphyrin Radical Anion and Radical Cation

The radical anions and radical cations of the two tautomers (1e and 1i) of 5,10,15,20-tetraphenyl N-confused free-base porphyrin have been studied using a combination of cyclic voltammetry, steady state absorption spectroscopy, and computational chemistry. N-Confused porphyrins (NCPs), alternatively called 2-aza-21-carba-5,10,15,20-tetraphenylporphyrins or inverted porphyrins, are of great interest for their potential as building blocks in assemblies designed for artificial photosynthesis, and understanding the absorption spectra of the corresponding radical ions is paramount to future studies in multicomponent arrays where electron-transfer reactions are involved. NCP 1e was shown to oxidize at a potential of E(ox) 0.65 V vs Fc(+)|Fc in DMF and reduce at E(red) -1.42 V, while the corresponding values for 1i in toluene were E(ox) 0.60 V and E(red) -1.64 V. The geometries of these radical ions were computed at the B3LYP/6-31+G(d)//B3LYP/6-31G(d) level in the gas phase and in solution using the polarizable continuum model (PCM). From these structures and that of H(2)TPP and its corresponding radical ions, the computed redox potentials for 1e and 1i were calculated using the Born-Haber cycle. While the computed reduction potentials and electron affinities were in excellent agreement with the experimental reduction potentials, the calculated oxidation potentials displayed a somewhat less ideal relationship with experiment. The absorption spectra of the four radical ions were also measured experimentally, with radical cations 1e(•+) and 1i(•+) displaying significant changes in the Soret and Q-band regions as well as new low energy absorption bands in the near-IR region. The changes in the absorption spectra of radical anions 1e(•-) and 1i(•-) were not as dramatic, with the changes occurring only in the Soret and Q-band regions. These results were favorably modeled using time-dependent density functional calculations at the TD-B3LYP/6-31+G(d)//B3LYP/6-31G(d) level. These results were also compared to the existing data of free base tetraphenylporphyrin and free base tetraphenylchlorin.

A novel non-catalytic synthesis method for zero- and two-dimensional B13C2nanostructures

Boron carbide nanoparticles and nanoflakes represent nano-building blocks for complex hierarchical assembly of nanoscale structures that exhibit ideal mechanical robustness. These nano-building blocks were synthesized by simply changing the mixing ratio of the solid precursors to influence the saturation condition of the process. As such, the ability to tune the nanostructures of boron carbide was achieved by controlling the concentration of gaseous boron oxide in the process with no catalyst involved in the growing process. The phase of the resulting nanostructures were found to be B13C2, which is a much desired phase because its hardness of close to 60 GPa is twice as hard as B4C. Nanoflakes were found to contain high degree of (101)-type twins with their boundaries likely to pass through the center of icosahedra in the structure. Nanoflakes with twinned microstructure are anticipated as a model nanostructure and can provide opportunities to fundamentally explore their mechanistic nature since twins have the potential in inhibiting the crack propagation, leading to toughening the materials.

Visible-Light-Absorbing Lindqvist-Type Polyoxometalates as Building Blocks for All-Inorganic Photosynthetic Assemblies

This study reports that polynuclear charge-transfer complexes consisting of Ce3+ and a Lindqvist-type polyoxometalate center, either W6O192− or Mo6O192−, function as an all-inorganic visible-light-absorbing chromophore. The polynuclear W6O19/Ce and Mo6O19/Ce complexes showed an intense absorption band from the UV region to 520 and 600 nm, respectively. The FTIR and Ce LIII-edge X-ray absorption measurements confirmed that the visible absorption is due to the oxo-bridged W6+/Ce3+ and Mo6+/Ce3+. As polyoxometalates have efficient redox and catalytic properties, their visible-light sensitization could provide a new building block for fabricating inorganic, molecular-based photosynthetic assemblies.

Flexible casting of modular self-aligning microfluidic assembly blocks

The recent shift among developers of microfluidic technologies toward modularized "plug and play" construction reflects the steadily increasing realization that, for many would-be users of microfluidic tools, traditional clean-room microfabrication is prohibitively complex and/or expensive. In this work, we present an advanced modular microfluidic construction scheme in which pre-fabricated microfluidic assembly blocks (MABs) can be quickly fashioned, without expertise or specialized facilities, into sophisticated microfluidic devices for a wide range of applications. Specifically, we describe three major advances to the MAB concept: (1) rapid production and extraction of MABs using flexible casting trays, (2) use of pre-coated substrates for simultaneous assembly and bonding, and (3) modification of block design to include automatic alignment and sealing structures. Finally, several exemplary applications of these MABs are demonstrated in chemical gradient synthesis, droplet generation, and total internal reflection fluorescence microscopy.

Impact of PWR spent fuel variations on back-end features of advanced fuel cycles with tru-fueled VHTR

Alternative strategies are being considered as management option for current spent nuclear fuel transuranics (TRU) inventory. Creation of transmutation fuels containing TRU for use in thermal and fast reactors is one of the viable strategies. Utilization of these advanced fuels will result in transmutation and incineration of the TRU. The objective of this study is to analyze the impact of conventional PWR spent fuel variations on TRU-fueled very high temperature reactor (VHTR) systems. The current effort is focused on prismatic core configuration operated under a single batch once-through fuel cycle option. IAEA’s nuclear fuel cycle simulation system (VISTA) was used to determine potential PWR spent fuel compositions. Additional composition was determined from the analysis of United States legacy spent fuel that is given in the Yucca Mountain Safety Assessment Report. A detailed whole-core 3-D model of the prismatic VHTR was developed using SCALE5.1 code system. The fuel assembly block model was based on Japan’s HTTR fuel block configuration. To establish a reference reactor system, calculations for LEU-fueled VHTR were performed and the results were used as the basis for comparative studies of the TRU-fueled systems. The LEU fuel is uranium oxide at 15% 235U enrichment. The results showed that the single-batch core lifetimes ranged between 5 and 7 years for all TRU fuels (3 years in LEU), providing prolonged operation on a single batch fuel loading. Transmutation efficiencies ranged between 19% and 27% for TRU-based fuels (13% in LEU). Total TRU material contents for disposal ranged between 730 and 808 kg per metric ton of initial heavy metal loading, reducing TRU inventory mass by as much as 27%. Decay heat and source terms of the discharged fuel were also calculated as part of the spent fuel disposal consideration. The results indicated strong potential of TRU-based fuel in VHTR.

The nucleoporin Nup188 controls passage of membrane proteins across the nuclear pore complex

All transport across the nuclear envelope (NE) is mediated by nuclear pore complexes (NPCs). Despite their enormous size, approximately 60 MD in vertebrates, they are comprised of only approximately 30 distinct proteins (nucleoporins or Nups), many of which form subcomplexes that act as building blocks for NPC assembly. One of these evolutionarily conserved subcomplexes, the Nup93 complex, is a major structural component linking the NPC to the membranes of the NE. Using in vitro nuclear assembly assays, we show that two components of the Nup93 complex, Nup188 and Nup205, are dispensable for NPC formation. However, nuclei lacking Nup188 increase in size by several fold compared with wild type. We demonstrate that this phenotype is caused by an accelerated translocation of integral membrane proteins through NPCs, suggesting that Nup188 confines the passage of membrane proteins and is thus crucial for the homeostasis of the different nuclear membranes.