Universal Building Block Research Articles

High-efficiency hybrid amorphous silicon grating couplers for sub-micron-sized lithium niobate waveguides.

We demonstrate hybrid amorphous silicon uniform grating couplers for efficient coupling between the standard single-mode fiber and sub-micron lithium niobate waveguides. The grating couplers exhibit coupling efficiency of -3.06 dB and 1-dB bandwidth of 55 nm. The amorphous silicon grating couplers can also provide a universal building block applicable to other photonic platforms such as silicon nitride waveguides, whose moderate refractive index values prevent high efficiency grating couplers to be fabricated in the native waveguide.

All three IP3 receptor subtypes generate Ca2+ puffs, the universal building blocks of IP3-evoked Ca2+ signals.

ABSTRACTAll three subtypes of inositol 1,4,5-trisphosphate receptor (IP3R) are intracellular Ca2+ channels that are co-regulated by IP3 and Ca2+. This allows IP3Rs to evoke regenerative Ca2+ signals, the smallest of which are Ca2+ puffs that reflect the coordinated opening of a few clustered IP3Rs. We use total internal reflection microscopy (TIRF) microscopy to record Ca2+ signals in HEK cells expressing all three IP3R subtypes or a single native subtype. Ca2+ puffs are less frequent in cells expressing one IP3R subtype, commensurate with them expressing fewer IP3Rs than wild-type cells. However, all three IP3R subtypes generate broadly similar Ca2+ puffs with similar numbers of IP3Rs contributing to each. This suggests that IP3R clusters may be assembled by conserved mechanisms that generate similarly sized clusters across different IP3R expression levels. The Ca2+ puffs evoked by IP3R2 had slower kinetics and more prolonged durations, which may be due to IP3 binding with greater affinity to IP3R2. We conclude that Ca2+ puffs are the building blocks for the Ca2+ signals evoked by all IP3Rs.

From C60 "trilliumons" to "trilliumenes:" Self-assembly of 2D fullerene nanostructures on metal-covered silicon and germanium.

We discovered a set of C60 nanostructures that appear to be constructed using a universal building block made of four C60 molecules on Si(111) or Ge(111) surfaces covered by an atomic layer of Tl, Pb, or their compound. The building block is a four-C60 cluster having a shape reminiscent of the three-petal flower "white trillium." Therefore, we call it "trilliumon" and the various 2D ordered nanostructures derived from it "trilliumenes." Self-assembly of the trilliumenes is a result of an intricate interplay among the adsorbed C60 molecules, metal atoms, and semiconductor substrates. Remarkably, all metal layers triggering formation of trilliumenes on the Si(111) surface have recently been reported to be the thinnest 2D superconductors. In this respect, the trilliumenes show promise to be 2D nanostructured superconductors whose properties are awaiting their exploration.

Late‐Stage Isotopic Carbon Labeling of Pharmaceutically Relevant Cyclic Ureas Directly from CO2

AbstractA robust, click‐chemistry‐inspired procedure for radiolabeling of cyclic ureas was developed. This protocol, suitable for all carbon isotopes (11C, 13C, 14C), is based on the direct functionalization of carbon dioxide: the universal building block for carbon radiolabeling. The strategy is operationally simple and reproducible in different radiochemistry centers, exhibits remarkably wide substrate scope with short reaction times, and demonstrates superior reactivity as compared to previously reported systems. With this procedure, a variety of pharmaceuticals and an unprotected peptide were labeled with high radiochemical efficiency.

Late-Stage Isotopic Carbon Labeling of Pharmaceutically Relevant Cyclic Ureas Directly from CO2.

A robust, click‐chemistry‐inspired procedure for radiolabeling of cyclic ureas was developed. This protocol, suitable for all carbon isotopes (11C, 13C, 14C), is based on the direct functionalization of carbon dioxide: the universal building block for carbon radiolabeling. The strategy is operationally simple and reproducible in different radiochemistry centers, exhibits remarkably wide substrate scope with short reaction times, and demonstrates superior reactivity as compared to previously reported systems. With this procedure, a variety of pharmaceuticals and an unprotected peptide were labeled with high radiochemical efficiency.

The Methylerythritol Phosphate Pathway: Promising Drug Targets in the Fight against Tuberculosis.

Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), is a severe infectious disease in need of new chemotherapies especially for drug-resistant cases. To meet the urgent requirement of new TB drugs with novel modes of action, the TB research community has been validating numerous targets from several biosynthetic pathways. The methylerythritol phosphate (MEP) pathway is utilized by Mtb for the biosynthesis of isopentenyl pyrophosphate (IPP) and its isomer dimethylallyl pyrophosphate (DMAPP), the universal five-carbon building blocks of isoprenoids. While being a common biosynthetic pathway in pathogens, the MEP pathway is completely absent in humans. Due to its unique presence in pathogens as well as the essentiality of the MEP pathway in Mtb, the enzymes in this pathway are promising targets for the development of new drugs against tuberculosis. In this Review, we discuss three enzymes in the MEP pathway: 1-deoxy-d-xylulose-5-phosphate synthase (DXS), 1-deoxy-d-xylulose-5-phosphate reductoisomerase (IspC/DXR), and 2 C-methyl-d-erythritol 2,4-cyclodiphosphate synthase (IspF), which appear to be the most promising antitubercular drug targets. Structural and mechanistic features of these enzymes are reviewed, as well as selected inhibitors that show promise as antitubercular agents.

Industrial Image Processing Applications as Orchestration of Web Services

Contemporary production lines often make extensive use of image recognition to achieve high levels of automation. Shorter product life cycles and smaller lot sizes force companies to adapt their processes very quickly. Still, industrial image processing algorithms typically run on dedicated computer systems next to the cameras, which is rather inflexible and leads to high costs for hardware and maintenance. In this paper, we propose a service-based architecture to tackle these problems. We divide image processing applications into universal building blocks, each of which is implemented as web service. The recognition application is conceived as a composition of these services, orchestrated using the Business Process Execution Language (BPEL). The composed application is provided with a standard industrial interface (OPC UA) for easy integration into the production process. This concept is evaluated by assessing proof-of-concept implementations. Main advantages (among others) are the flexible reuse of existing image processing operations and applications, and the freedom to implement services independently using the preferred language, framework and platform. Challenges are real-time constraints, which can be alleviated by emerging technologies like Time Sensitive Networking (TSN).

Biomimetic, Strong, Tough, and Self-Healing Composites Using Universal Sealant-Loaded, Porous Building Blocks.

Many natural materials, such as nacre and dentin, exhibit multifunctional mechanical properties via structural interplay between compliant and stiff constituents arranged in a particular architecture. Herein, we present, for the first time, the bottom-up synthesis and design of strong, tough, and self-healing composite using simple but universal spherical building blocks. Our composite system is composed of calcium silicate porous nanoparticles with unprecedented monodispersity over particle size, particle shape, and pore size, which facilitate effective loading and unloading with organic sealants, resulting in 258% and 307% increases in the indentation hardness and elastic modulus of the compacted composite. Furthermore, heating the damaged composite triggers the controlled release of the nanoconfined sealant into the surrounding area, enabling moderate recovery in strength and toughness. This work paves the path towards fabricating a novel class of biomimetic composites using low-cost spherical building blocks, potentially impacting bone-tissue engineering, insulation, refractory and constructions materials, and ceramic matrix composites.

Post-Cross-Linked Molecular Imprinting with Functional Polymers as a Universal Building Block for Artificial Polymeric Receptors

A post-cross-linked molecular imprinting (PC-MI) technique utilizing a functional polymer (FP) with interacting and post-cross-linking groups was developed to create molecularly imprinted polymeric (MIP) receptors. Molecular recognition cavities were formed in the cross-linked polymer matrix by a posteriori cross-linking of the FP with template molecules using photoirradiation. These cavities could be easily tuned to recognize the target molecules by changing the template using a common FP as a universal building block. Thus, precise chiral recognition cavities were successfully created using PC-MI and optimizing the molar ratio of the functional groups between the FP and the target molecules, which suppressed the nonspecific binding of the off-target molecules. Furthermore, the morphology of the MIPs could be changed from bulk to particles. This study provides a facile and efficient synthetic route for MIPs with tailor-made properties. Thus, PC-MI can be utilized to create molecular recognition elements ...

Engineering the biocatalytic selectivity of iridoid production in Saccharomyces cerevisiae

Monoterpene indole alkaloids (MIAs) represent a structurally diverse, medicinally essential class of plant derived natural products. The universal MIA building block strictosidine was recently produced in the yeast Saccharomyces cerevisiae, setting the stage for optimization of microbial production. However, the irreversible reduction of pathway intermediates by yeast enzymes results in a non-recoverable loss of carbon, which has a strong negative impact on metabolic flux. In this study, we identified and engineered the determinants of biocatalytic selectivity which control flux towards the iridoid scaffold from which all MIAs are derived. Development of a bioconversion based production platform enabled analysis of the metabolic flux and interference around two critical steps in generating the iridoid scaffold: oxidation of 8-hydroxygeraniol to the dialdehyde 8-oxogeranial followed by reductive cyclization to form nepetalactol. In vitro reconstitution of previously uncharacterized shunt pathways enabled the identification of two distinct routes to a reduced shunt product including endogenous ‘ene’-reduction and non-productive reduction by iridoid synthase when interfaced with endogenous alcohol dehydrogenases. Deletion of five genes involved in α,β-unsaturated carbonyl metabolism resulted in a 5.2-fold increase in biocatalytic selectivity of the desired iridoid over reduced shunt product. We anticipate that our engineering strategies will play an important role in the development of S. cerevisiae for sustainable production of iridoids and MIAs.

Large N correlation functions mathcal{N} = 2 superconformal quivers

Using supersymmetric localization, we consider four-dimensional mathcal{N} = 2 superconformal quiver gauge theories obtained from {mathbb{Z}}_n orbifolds of mathcal{N} = 4 Super Yang-Mills theory in the large N limit at weak coupling. In particular, we show that: 1) The partition function for arbitrary couplings can be constructed in terms of universal building blocks. 2) It can be computed in perturbation series, which converges uniformly for |λI | < π2, where λI are the ’t Hooft coupling of the gauge groups. 3) The perturbation series for two-point functions can be explicitly computed to arbitrary orders. There is no universal effective coupling by which one can express them in terms of correlators of the mathcal{N} = 4 theory. 4) One can define twisted and untwisted sector operators. At the perturbative orbifold point, when all the couplings are the same, the correlators of untwisted sector operators coincide with those of mathcal{N} = 4 Super Yang-Mills theory. In the twisted sector, we find remarkable cancellations of a certain number of planar loops, determined by the conformal dimension of the operator.

Mitochondria are not captive bacteria

Lynn Sagan's conjecture (1967) that three of the fundamental organelles observed in eukaryote cells, specifically mitochondria, plastids and flagella were once free-living primitive (prokaryotic) cells was accepted after considerable opposition. Even though the idea was swiftly refuted for the specific case of origins of flagella in eukaryotes, the symbiosis model in general was accepted for decades as a realistic hypothesis to describe the endosymbiotic origins of eukaryotes. However, a systematic analysis of the origins of the mitochondrial proteome based on empirical genome evolution models now indicates that 97% of modern mitochondrial protein domains as well their homologues in bacteria and archaea were present in the universal common ancestor (UCA) of the modern tree of life (ToL). These protein domains are universal modular building blocks of modern genes and genomes, each of which is identified by a unique tertiary structure and a specific biochemical function as well as a characteristic sequence profile. Further, phylogeny reconstructed from genome-scale evolution models reveals that Eukaryotes and Akaryotes (archaea and bacteria) descend independently from UCA. That is to say, Eukaryotes and Akaryotes are both primordial lineages that evolved in parallel. Finally, there is no indication of massive inter-lineage exchange of coding sequences during the descent of the two lineages. Accordingly, we suggest that the evolution of the mitochondrial proteome was autogenic (endogenic) and not endosymbiotic (exogenic).

Synthetic Approach to Argpyrimidine as a Tool for Investigating Nonenzymatic Posttranslational Modification of Proteins

Nonenzymatic posttranslational modifications (nPTMs) of proteins are involved in age-related, metabolic and other diseases and need to be investigated at the molecular level. Here, we describe how we used organic synthesis to enable the study of the effect of argpyrimidine (Apy), an nPTM that forms at arginine residues, on one of its target proteins. We developed an efficient approach to Apy as a universal building block for Fmoc-based solid-phase peptide synthesis that allows for the construction of peptides containing this nPTM in predetermined positions. Moreover, a straightforward one-step synthesis of protecting-group-free Apy was achieved, which enabled the preparation of gram-quantities of this noncanonical amino acid that can serve as a biomarker or a feedstock in construction of Apy-containing proteins via the expanded genetic code methods.

The Methylerythritol Phosphate Pathway to Isoprenoids.

Isoprenoids constitute one of the most diverse classes of natural products. As a compound class, they are essential to basic metabolic processes including cell-wall biosynthesis, post-translational protein modifications, and signaling. In addition, isoprenoid secondary metabolites are highly valuable natural products with a wide range of biotechnological applications. The biosynthesis of their two universal building blocks, isopentenyl diphosphate and dimethylallyl diphosphate, was thought to proceed exclusively by way of mevalonate as a key intermediate until a novel pathway involving methylerithritol phosphate (MEP) was discovered in the early 1990s. In this review, we describe the seven enzymes of the MEP pathway, along with their discoveries, three-dimensional structures, and mechanisms. The latter include examples of remarkable enzyme catalysis including an unusual cytidilation reaction and the use of iron-sulfur cluster cofactors in reductive ring opening and hydroxy-group elimination. Furthermore, isoprenoid biosynthesis shows a characteristic species distribution. A brief overview highlights the MEP pathway's potential as a selective drug target, which is absent in humans but essential to the survival of many important bacterial and apicomplexan pathogens.

Spiking Neurons as Universal Building Blocks for Hybrid Systems

The synchronization of oscillatory activity in networks of networks is usually implemented through coupling the state variables describing the dynamics of each network. Here we study another but complementary mechanism of synchronization in unidirectional chains of network motifs based on a learning process. A driver motif, acting as a teacher, exhibits winner-less competition dynamics, while a driven motif, a learner, tunes its internal couplings according to the observed oscillations in the teacher. We show that under appropriate training learner network motifs in a chain can progressively copy the connectivity pattern of the teacher (first motif). In average the time interval required for pattern replication grows linearly with the chain size, hence the learning process does not blow up and at the end we observe phase synchronized oscillations along the chain. We also show that in a learning chain closed into a ring the network motifs come to a consensus, i.e., to a state with the same connectivity pattern corresponding to the mean initial pattern averaged over all network motifs.

Bone‐Inspired Materials by Design: Toughness Amplification Observed Using 3D Printing and Testing

Inspired by the fact that nature provides multifunctional composites by using universal building blocks, the authors design and test synthetic composites with a pattern inspired by the microstructure of cortical bone. Using a high‐resolution multimaterial 3D printer, the authors are able to manufacture samples and investigate their fracture behavior in mechanical tests. The authors’ results demonstrate that the bone‐inspired design is critical for toughness amplification and balance with material strength. The failure modes of the authors’ synthetic composites show similarities with the cortical bone, like crack deflection and branching, constrained microcracking, and fibril bridging. The authors’ results confirm that our design is eligible to reproduce the fracture and toughening mechanism of bone.

(3S)-4-[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]-3-methylbutan-1-ol—A universal building block for the synthesis of principal fragments of amphidinolides G and H

A new scheme has been proposed for the synthesis of cytotoxic macrocyclic lactones, amphidinolides G and H. Synthetic analogs of the C7‒C14, C15‒C19, and C20‒C26 fragments of amphidinolides G and H have been prepared from the same starting compound, (3S)-4-[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]-3-methylbutan-1-ol. The developed procedures and obtained products may be used in the synthesis of related compounds containing similar structural fragments.

Orthologs of the archaeal isopentenyl phosphate kinase regulate terpenoid production in plants.

Terpenoids, compounds found in all domains of life, represent the largest class of natural products with essential roles in their hosts. All terpenoids originate from the five-carbon building blocks, isopentenyl diphosphate (IPP) and its isomer dimethylallyl diphosphate (DMAPP), which can be derived from the mevalonic acid (MVA) and methylerythritol phosphate (MEP) pathways. The absence of two components of the MVA pathway from archaeal genomes led to the discovery of an alternative MVA pathway with isopentenyl phosphate kinase (IPK) catalyzing the final step, the formation of IPP. Despite the fact that plants contain the complete classical MVA pathway, IPK homologs were identified in every sequenced green plant genome. Here, we show that IPK is indeed a member of the plant terpenoid metabolic network. It is localized in the cytosol and is coexpressed with MVA pathway and downstream terpenoid network genes. In planta, IPK acts in parallel with the MVA pathway and plays an important role in regulating the formation of both MVA and MEP pathway-derived terpenoid compounds by controlling the ratio of IP/DMAP to IPP/DMAPP. IP and DMAP can also competitively inhibit farnesyl diphosphate synthase. Moreover, we discovered a metabolically available carbon source for terpenoid formation in plants that is accessible via IPK overexpression. This metabolite reactivation approach offers new strategies for metabolic engineering of terpenoid production.

A factorization approach to next-to-leading-power threshold logarithms

Threshold logarithms become dominant in partonic cross sections when the selected final state forces gluon radiation to be soft or collinear. Such radiation factorizes at the level of scattering amplitudes, and this leads to the resummation of threshold logarithms which appear at leading power in the threshold variable. In this paper, we consider the extension of this factorization to include effects suppressed by a single power of the threshold variable. Building upon the Low-Burnett-Kroll-Del Duca (LBKD) theorem, we propose a decomposition of radiative amplitudes into universal building blocks, which contain all effects ultimately responsible for next-to-leading power (NLP) threshold logarithms in hadronic cross sections for electroweak annihilation processes. In particular, we provide a NLO evaluation of the "radiative jet function", responsible for the interference of next-to-soft and collinear effects in these cross sections. As a test, using our expression for the amplitude, we reproduce all abelian-like NLP threshold logarithms in the NNLO Drell-Yan cross section, including the interplay of real and virtual emissions. Our results are a significant step towards developing a generally applicable resummation formalism for NLP threshold effects, and illustrate the breakdown of next-to-soft theorems for gauge theory amplitudes at loop level.

A conserved histidine modulates HSPB5 structure to trigger chaperone activity in response to stress-related acidosis.

Small heat shock proteins (sHSPs) are essential 'holdase' chaperones that form large assemblies and respond dynamically to pH and temperature stresses to protect client proteins from aggregation. While the alpha-crystallin domain (ACD) dimer of sHSPs is the universal building block, how the ACD transmits structural changes in response to stress to promote holdase activity is unknown. We found that the dimer interface of HSPB5 is destabilized over physiological pHs and a conserved histidine (His-104) controls interface stability and oligomer structure in response to acidosis. Destabilization by pH or His-104 mutation shifts the ACD from dimer to monomer but also results in a large expansion of HSPB5 oligomer states. Remarkably, His-104 mutant-destabilized oligomers are efficient holdases that reorganize into structurally distinct client-bound complexes. Our data support a model for sHSP function wherein cell stress triggers small perturbations that alter the ACD building blocks to unleash a cryptic mode of chaperone action.