Left-handed Helix Research Articles

DbStRiPs: Database of structural repeats in proteins.

Recent interest in repeat proteins has arisen due to stable structural folds, high evolutionary conservation and repertoire of functions provided by these proteins. However, repeat proteins are poorly characterized because of high sequence variation between repeating units and structure-based identification and classification of repeats is desirable. Using a robust network-based pipeline, manual curation and Kajava's structure-based classification schema, we have developed a database of tandem structural repeats, Database of Structural Repeats in Proteins (DbStRiPs). A unique feature of this database is that available knowledge on sequence repeat families is incorporated by mapping Pfam classification scheme onto structural classification. Integration of sequence and structure-based classifications help in identifying different functional groups within the same structural subclass, leading to refinement in the annotation of repeat proteins. Analysis of complete Protein Data Bank revealed 16,472 repeat annotations in 15,141 protein chains, one previously uncharacterized novel protein repeat family (PRF), named left-handed beta helix, and 33 protein repeat clusters (PRCs). Based on their unique structural motif, ~79% of these repeat proteins are classified in one of the 14 PRFs or 33 PRCs, and the remaining are grouped as unclassified repeat proteins. Each repeat protein is provided with a detailed annotation in DbStRiPs that includes start and end boundaries of repeating units, copy number, secondary and tertiary structure view, repeat class/subclass, disease association, MSA of repeating units and cross-references to various protein pattern databases, human protein atlas and interaction resources. DbStRiPs provides easy search and download options to high-quality annotations of structural repeat proteins (URL: http://bioinf.iiit.ac.in/dbstrips/).

Omnidirectional Circularly Polarized Antenna Based on Counter-Wound Helices

An innovative counter-wound helical antenna with omnidirectional circular polarization (OCP) is reported in this communication, with a significantly enhanced radiation resistance and matching bandwidth compared with the conventional normal-mode CP helix counterpart. The antenna is realized by combining several helical radiators with opposite winding directions. A three-segment OCP counter-wound helix is studied, featuring one right-handed helix in the middle and two left-handed helices sandwiching it from the top and the bottom. Besides achieving a stable OCP pattern with gain variations of less than 0.2 dB, the radiation resistance at the operating frequency f <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">0</sub> is increased to 26.7 Ω compared with 3.3 Ω of the traditional uniform-wound helix. Theoretical analysis and simulations are presented. To further enhance the radiation resistance, a five-segment helical antenna prototype is demonstrated and tested. The radiation resistance rises further to 80.9 Ω at f <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">0</sub> and the measured matching bandwidth reaches 2.8%, surpassing that of the conventional OCP helix by four times. Stable OCP radiation with a realized gain of up to 2.5 dBic is observed. Being compact and simple, the developed helical antenna could represent an ideal candidate for various wireless applications, for example, device-to-device (D2D) communications that require OCP radiations.

Molecular dynamic simulation: Structural insights of multi-stranded curdlan in aqueous solution

In this work, by using molecular dynamic simulation we provide microscale structure information which helps to reveal the molecular mechanisms concerning the multi-chain conformational behavior of short curdlan. Through simulations starting with different conformations of curldan dodecasaccharides, it is found that the right-handed triple helix is thermodynamically the most stable conformation in aqueous solutions, which is well maintained and stabilized by an inter-strand hydrogen bonding network of the C2 hydroxyls. Unlike any predicted forms, the inter-strand hydrogen bonds exhibit a left-handed double helix pattern with preferred global orientations. Temperature REMD results suggest that the formation of triple helix is temperature sensitive, but the already formed triple helix is not. Investigation of curdlan with numbers of repeating units from 3 to 12 captures a critical value of 6, which in a way elucidates the relationship between the formation of triple helix and the chain length.

Therapeutic delivery with V-amylose.

The helical structure of V-amylose offering a superior encapsulation affinity compared with the other polysaccharides, especially toward the amphiphilic or hydrophobic molecules; in addition to providing a higher resistance toward enzymatic hydrolysis support its applications as a potential drug delivery vehicle. Mainly, the glycosidic linkages and -CH2 - groups forming the hydrophobic cavity of V-amylose helix, and the glycosyl hydroxyl groups constituting its hydrophilic periphery promote the loading of a diverse range of molecules via van der Waals forces and hydrogen bonding interactions. These properties enable a high-loading efficiency, targeted delivery, and controlled release of the cargo drug molecules by V-amylose. Besides, V-amylose presents characteristics of an ideal drug delivery system, such as biocompatibility, physiological benevolence, nonimmunogenicity, and biodegradability. The V-amylose polysaccharide chains fold into left-handed single helix comprising of six glucose units in each turn having a pitch height of 7.91-8.17 Å. These structural features of V-amylose differentiate it from the parent amylose polysaccharide and enable the accommodation and nanoencapsulation of a wide range of therapeutics in the former. The tightly packed helical structure of V-amylose provides extraordinary resistance toward digestion by amylase compared with the linear polysaccharides, which supports the application of V-amylose as controlled drug release systems. The activity of the amylase enzyme produced by salivary glands, pancreas, gastrointestinal tract, and gut microbiota on amylose-based drug delivery vehicles promote enzyme-sensitive controlled oral and colon-specific release of the encapsulated drug. The single helical V-amylose with hydrophobic core and hydrophilic periphery forms inclusion complexes that improve the absorption and permeation of drugs having a high clogP index. The present commentary highlights the distinguished features of V-amylose as an imminent drug delivery system.

Copolyaspartates: Uncovering Simultaneous Thermo and Magnetoresponsiveness

A series of poly-β-benzyl-l-aspartate-co-poly-β-phenethyl-l-aspartates varying in their copolymer composition as well as with selectively introduced deuterium labels in the backbone or the side-chain were synthesized and their temperature-dependent conformation and orientation with respect to an external magnetic field were characterized by measuring 2H quadrupolar splittings [nuclear magnetic resonance (NMR) spectroscopy] and circular dichroism. All copolymers demonstrate a temperature-dependent change of their helical conformation from right-handed to left-handed (helix reversal) and a change of their alignment from perpendicular to parallel with respect to the magnetic field in an anisotropic solution (helix realignment) at different temperatures. Both effects react differently to a change of copolymer composition, but are concentration, dispersity, and molecular weight independent as well as unaffected by the initiator used for polymerization. The helix realignment by 90° in a magnetic field has not been observed previously for these copolyaspartates. Its existence is proven directly by measurement of the quadrupolar splitting of the specifically labeled polymers and comparison to calculated quadrupolar splittings. Furthermore, the temperature of both transitions was found to be dependent on deuteration at the N-position. The uncovering of the thermo and magnetoresponsiveness will lead to an improved understanding and application scope of the copolyaspartates (e.g., in their use as alignment media in NMR spectroscopy).

Hydrodynamic Properties of the Sun’s Giant Cellular Flows

Abstract Measurements of the large cellular flows on the Sun were made by local correlation tracking of features (supergranules) seen in full-disk Doppler images obtained by the Helioseismic and Magnetic Imager (HMI) instrument on the NASA Solar Dynamics Observatory (SDO) satellite. Several improvements made to the local correlation tracking method allowed for more precise measurements of these flows. Measurements were made hourly over the nearly ten years of the mission-to-date. A four-hour time-lag between images was determined to give the best results as a compromise between increased feature displacement and decreased feature evolution. The hourly measurements were averaged over the 34 days that it takes to observe all longitudes at all latitudes to produce daily maps of the latitudinal and longitudinal velocities. Analyses of these flow maps reveal many interesting characteristics of these large cellular flows. While flows at all latitudes are largely in the form of vortices with left-handed helicity in the north and right-handed helicity in the south, there are key distinctions between the low-latitude and high-latitude cells. The low-latitude cells have roughly circular shapes, lifetimes of about one month, rotate nearly rigidly, do not drift in latitude, and do not exhibit any correlation between longitudinal and latitudinal flow. The high-latitude cells have long extensions that spiral inward toward the poles and can wrap nearly completely around the Sun. They have lifetimes of several months, rotate differentially with latitude, drift poleward at speeds approaching 2 m s−1, and have a strong correlation between prograde and equatorward flows. Spherical harmonic spectral analyses of maps of the divergence and curl of the flows confirm that the flows are dominated by the curl component with rms velocities of about 12 m s−1 at wavenumber ℓ = 10. Fourier transforms in time over 1024 daily records of the spherical harmonic spectra indicate two notable components—an m = ±ℓ feature representing the low-latitude component and an m = ±1 feature representing the high-latitude component. The dispersion relation for the low-latitude component is well represented by that derived for Rossby waves or r-modes. The high-latitude component has a constant temporal frequency for all ℓ indicating features advected by differential rotation at rates representative of the base of the convection zone high latitudes. The poleward motions of these features further suggest that the high-latitude meridional flow at the base of the convection zone is poleward—not equatorward.

Conformational transition of Poly-L-proline studied by IR, NMR, and SAXS

Poly-l-proline (PLP) takes two extreme local conformations, right-handed helix (Helix-I) and left-handed helix (Helix-II) and two overall conformations at a steady-state, PLP-I and –II, each of which is constructed by sequences of Helix-I and –II, respectively. The study with IR and proton NMR spectroscopy has verified that PLP-I dissolved in glacial acetic acid is gradually converted into PLP-II (forward-mutarotation) and PLP-II dissolved in a mixture of glacial acetic acid and n-propanol is gradually converted into PLP-I (reverse-mutarotation), and has roughly evaluated the rate of the conformational change: It takes ca. 48 hrs. and ca. 40–50 h at 25 °C, respectively, for the forward- and reverse-mutarotation process to reach the middle stage. The analysis of the SAXS data has shown that the conformation of PLP at the middle stage of the forward mutarotation process is represented by joining alternatively rodlike structure of Helix-I and –II, which has equal 180 ± 90 proline residues per a helical rod, whereas the overall conformation of PLP-II dissolved in CD3COOD is represented by an intact helical rod or an interrupted helical rod having a few breaking-points. These data suggest that the conformational transition of PLP would proceed in a zipper-like pattern.

Supramolecular Architecture through Self-Organization of Janus-Faced Homoazanucleosides.

Design of Janus-faced or double-headed homoazanucleosides with the possibility to undergo self-organization through base pairing has been conceptualized and accomplished. The synthetic strategy demonstrates the unique ability to introduce two similar or complementary nucleobases on opposite arms of a chiral polyhydroxypyrrolidine while also ensuring that their faces are anti to each other to allow only intermolecular interactions between the nucleobases, an essential requisite for self-assembly. Single-crystal X-ray structures were determined for all three types of homoazanucleosides, one possessing two adenine molecules, the other with two thymine moieties, and the third containing both adenine and thymine. The crystal structures of all three display noncovalent interactions, including Watson-Crick base pairing, Hoogsteen H-bonding, and π-π stacking, resulting in unusual supramolecular patterns. The most striking supramolecular motif among them, which emerged from the crystal structure of the homoazanucleoside containing both adenine and thymine, is a left-handed helix formed through Watson-Crick pairing between nucleobases. The present study thus forms a prelude to the design of Janus-faced building blocks to establish helical pillars as well as lateral branches that together define a three-dimensional (3D) lattice. The ready accessibility of these molecules is expected to spur the next generation of discoveries in the design of functional nanomaterials.

Insight into the Assembling Mechanism of Cryptococcus Capsular Glucuronoxylomannan Based on Molecular Dynamics Simulations.

Cryptococcus spp. is an invasive fungal pathogen and causes life-threatening cryptococcosis. Opportunistic cryptococcal infections among the immunocompromised population are mostly caused by Cryptococcus neoformans, whereas the geographical dissemination of Cryptococcus gattii in recent years has threatened lives of even immunocompetent people. The capsule, mainly composed of glucuronoxylomannan (GXM) polysaccharides, plays important roles in the virulence of Cryptococcus spp. The assembling mechanism of GXM polysaccharides into the capsule is little understood because of insufficient experimental data. Molecular modeling and molecular dynamics simulation provide insight into the assembling process. We first built GXM oligosaccharide models of serotypes D, A, B, and C and extracted their secondary structure information from simulation trajectories. All the four mainchains tend to take the nearly twofold helical conformation, whereas peripheral sidechains prefer to form left-handed helices, which are further stabilized by intramolecular hydrogen bonds. Based on the obtained secondary structure information, GXM polysaccharide arrays were built to simulate capsule-assembling processes of C. neoformans and C. gattii using serotypes A and C as representatives, respectively. Trajectory analysis illustrates that electrostatic neutralization of acidic sidechain residues of GXM is a prerequisite for capsule assembling, followed by formation of intermolecular hydrogen bond networks. Further insight into the assembling mechanism of GXM polysaccharides provides the possibility to develop novel treatment and prevention solutions for cryptococcosis.

Protein-induced B-Z transition of DNA duplex containing a 2′-OMe guanosine

Structural transformation of the canonical right-handed helix, B-DNA, to the non-canonical left-handed helix, Z-DNA, can be induced by the Zα domain of the human RNA editing enzyme ADAR1 (hZαADAR1). To characterize the site-specific preferences of binding and structural changes in DNA containing the 2′-O-methyl guanosine derivative (mG), titration of the imino proton spectra and chemical shift perturbations were performed on hZαADAR1 upon binding to Z-DNA. The structural transition between B–Z conformation as the changing ratio between DNA and protein showed a binding affinity of the modified DNA onto the Z-DNA binding protein similar to wild-type DNA or RNA. The chemical shift perturbation results showed that the overall structure and environment of the modified DNA revealed DNA-like properties rather than RNA-like characteristics. Moreover, we found evidence for two distinct regimes, “Z-DNA Sensing” and “Modification Sensing”, based on the site-specific chemical shift perturbation between the DNA (or RNA) binding complex and the modified DNA–hZαADAR1 complex. Thus, we propose that modification of the sugar backbone of DNA with 2′-O-methyl guanosine promotes the changes in the surrounding α3 helical structural segment as well as the non-perturbed feature of the β-hairpin region.

Characterization of left-handed beta helix-domains, and identification and functional annotation of proteins containing such domains.

Only about 0.3% of the entries in UniProt database have manually curated annotation. Annotation at the molecular level often relies on low-throughput one-protein-at-a-time approach. Computational methods bridge this gap by assigning function based on sequence and/or fold similarity. Left-handed beta helix (LbH) consists of three repeating six-stranded beta-strands forming an 18-mer turn of the helix. Analysis of LbH-domains showed that variations are found in the number of residues in a beta-strand (5-7, 6 being the most common), number of turns (4-10) of the helix, insertions of one or more loops of variable length (0-36 residues), and the location of loop insertion. An 18-mer HMM profile was created which identifies LbH-domain containing proteins using sequence as the only input; the number of false positives is zero when proteins tested were those with known 3D structures. 136 474 entries of TrEMBL database were found to contain LbH-domain. Rules developed by analyzing LbH-domain containing acyltransferases, gamma-class carbonic anhydrases, and nucleotidyltransferases have led to the annotation of 17 389 TrEMBL entries which currently have no functional tag.

What Came First: The Helix or the H2O?

Jiang, Tian, and colleagues observe long-range interactions between two complementary DNA strands, resulting in an ordered chain of helical water. This hidden conformation of water has been observed, but the helix is commonly associated with biomolecules. Perhaps water—necessary for biological processes—is the key driver of the predominance of helices.

Constituent Isomerism-Induced Quasicrystal and Frank–Kasper σ Superlattices Based on Nanosized Shape Amphiphiles

Naturally, subtle variations in the chemical structures of constituent molecules may significantly affect their multiscale spatial arrangements, properties, and functions. Deceptively simple spheri...

The Effect of Calcium and Halide Ions on the Gramicidin A Molecular State and Antimicrobial Activity.

Gramicidin A (gA) forms several convertible conformations in different environments. In this study, we investigated the effect of calcium halides on the molecular state and antimicrobial activity of gramicidin A. The molecular state of gramicidin A is highly affected by the concentration of calcium salt and the type of halide anion. Gramicidin A can exist in two states that can be characterized by circular dichroism (CD), mass, nuclear magnetic resonance (NMR) and fluorescence spectroscopy. In State 1, the main molecular state of gramicidin A is as a dimer, and the addition of calcium salt can convert a mixture of four species into a single species, which is possibly a left-handed parallel double helix. In State 2, the addition of calcium halides drives gramicidin A dissociation and denaturation from a structured dimer into a rapid equilibrium of structured/unstructured monomer. We found that the abilities of dissociation and denaturation were highly dependent on the type of halide anion. The dissociation ability of calcium halides may play a vital role in the antimicrobial activity, as the structured monomeric form had the highest antimicrobial activity. Herein, our study demonstrated that the molecular state was correlated with the antimicrobial activity.

A penalized spline fitting method to optimize geometric parameters of arterial centerlines extracted from medical images

In order to grasp the spatial and temporal evolution of vascular geometry, three-dimensional (3D) arterial bending structure and geometrical changes of arteries and stent grafts (SG) must be quantified using geometrical parameters such as curvature and torsion along the vasculature centerlines extracted from medical images. Here, we develop a robust method for constructing smooth centerlines based on a spline fitting method (SFM) such that the optimized geometric parameters of curvature and torsion can be obtained independently of digitization noise in the images. Conventional SFM consists of the 3rd degree spline basis function and 2nd derivative penalty term. In contrast, the present SFM uses the 5th degree spline basis function and 3rd and 4th derivative penalty terms, the coefficients of which are derived by the Akaike information criterion. The results show that the developed SFM can reduce the errors of curvature and torsion compared to conventional SFM. We then apply the present SFM to the centerline of the SG in an abdominal aortic aneurysm (AAA), and those of bilateral internal carotid arteries (ICA) in 6 cases: 3 cases with aneurysms and 3 cases without any aneurysm. The SG centerlines were obtained from temporal medical images at three scan times. The strong peak of the curvature could be clearly observed in the distal area of the SG, the inversion of the torsion at 0 months in the middle area of SG disappeared over time, and the torsions around the SG bifurcation at the three time periods were inverted. The curvature-torsion graphs along the ICA centerlines superimposing five aneurysmal positions were useful for investigating the relationship between arterial bending structure and aneurysmal positions. Both ICAs had curvature peak values higher than 0.4 within the ICA syphons. The ICA torsion graphs indicated that left and right ICA tended to be a right- and left-handed helix, respectively. In the left ICA syphon, the biggest aneurysm could be observed downstream of the salient torsion inversion. All aneurysms for 3 cases were positioned at the downstream of the inverted torsion.

Bacterial Cellulose Nanocomposites: Morphology and Mechanical Properties.

Bacterial cellulose (BC) is a promising material for biomedical applications due to its unique properties such as high mechanical strength and biocompatibility. This article describes the microbiological synthesis, modification, and characterization of the obtained BC-nanocomposites originating from symbiotic consortium Medusomyces gisevii. Two BC-modifications have been obtained: BC-Ag and BC-calcium phosphate (BC-Ca3(PO4)2). Structure and physicochemical properties of the BC and its modifications were investigated by scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDX), atomic force microscopy (AFM), and infrared Fourier spectroscopy as well as by measurements of mechanical and water holding/absorbing capacities. Topographic analysis of the surface revealed multicomponent thick fibrils (150–160 nm in diameter and about 15 µm in length) constituted by 50–60 nm nanofibrils weaved into a left-hand helix. Distinctive features of Ca-phosphate-modified BC samples were (a) the presence of 500–700 nm entanglements and (b) inclusions of Ca3(PO4)2 crystals. The samples impregnated with Ag nanoparticles exhibited numerous roundish inclusions, about 110 nm in diameter. The boundaries between the organic and inorganic phases were very distinct in both cases. The Ag-modified samples also showed a prominent waving pattern in the packing of nanofibrils. The obtained BC gel films possessed water-holding capacity of about 62.35 g/g. However, the dried (to a constant mass) BC-films later exhibited a low water absorption capacity (3.82 g/g). It was found that decellularized BC samples had 2.4 times larger Young’s modulus and 2.2 times greater tensile strength as compared to dehydrated native BC films. We presume that this was caused by molecular compaction of the BC structure.

Spiranthes sinensis-Inspired Circular Polarized Luminescence in a Solid Block Copolymer Film with a Controllable Helix.

Chiral materials with circular polarized luminescence (CPL) have attracted much interest because of their extensive optical information and remarkable sensitivity. Inspired by the helical template in Spiranthes sinensis, we propose here a general and flexible method for fabricating solid CPL materials using a block copolymer-formed helix as a template. A chiral arrangement of various nonchiral fluorescent molecules was obtained in the block copolymer-based hybrid film. An excimer chiralty rule was found for the CPL emission of nonchiral fluorescent molecules: a right-handed helix induced left-handed CPL emission and a left-handed helix induced right-handed CPL emission. A dissipative particle dynamics simulation showed that such an antihelical effect is related to the length between the adjacent interacting points of nonchiral fluorescent molecules along the helical structure. Furthermore, the fluorescent films had a high dissymmetric factor for CPL emission, and thus, the films provide a general and flexible platform for designing and preparing advanced functional chiroptical materials.

Coexistence of Left- and Right-Handed 12/10-Mixed Helices in Cyclically Constrained β-Peptides and Directed Formation of Single-Handed Helices upon Site-Specific Methylation.

The inherent conformational preferences of the neutral β-peptide foldamer series, Ac-(ACHC)n-NHBn, n = 2-4, are studied in the gas phase using conformation-specific IR-UV double resonance methods. The cyclically constrained chiral β-amino acid cis-2-aminocyclohexane carboxylic acid (ACHC) is designed to bring both right- and left-handed helices into close energetic proximity. Comparison of the infrared spectra in the NH stretch and amide I/II regions with the predictions of DFT calculations lead to the unambiguous assignment of four out of the six observed conformations of the molecules in this series, while corroborating computational and spectral evidence, affords tentative assignments of the remaining two conformers for which IR data were not recorded. The observed structures fall into one of two conformational families: a right-handed 12/10-mixed helix or its "cap-disrupted" left-handed helical analogue, which coexist with significant populations. Site-specific and stereospecific methylation on the cyclohexane backbone at the dipeptide (n = 2) level is also tested as a means to sterically lock in a predetermined cyclohexane chair conformation. These substitutions are proven to be a means of selectively driving formation of one helical screw sense or the other. Calculated relative energies and free energies of all possible structures for the molecules provide strong supporting evidence that the rigid nature of the ACHC residue confers unusual stability to the 12/10-mixed helix conformation, regardless of local environment, temperature, or C-terminal capping unit. The simultaneous presence of both handed helices offers unique opportunities for future studies of their interconversion.

Cryo-EM structure of an amyloid fibril formed by full-length human prion protein.

Prion diseases are caused by the misfolding of prion protein (PrP). Misfolded PrP forms protease-resistant aggregates in vivo (PrPSc) that are able to template the conversion of the native form of the protein (PrPC), a property shared by in vitro-produced PrP fibrils. Here we produced amyloid fibrils in vitro from recombinant, full-length human PrPC (residues 23-231) and determined their structure using cryo-EM, building a model for the fibril core comprising residues 170-229. The PrP fibril consists of two protofibrils intertwined in a left-handed helix. Lys194 and Glu196 from opposing subunits form salt bridges, creating a hydrophilic cavity at the interface of the two protofibrils. By comparison with the structure of PrPC, we propose that two α-helices in the C-terminal domain of PrPC are converted into β-strands stabilized by a disulfide bond in the PrP fibril. Our data suggest that different PrP mutations may play distinct roles in modulating the conformational conversion.

Bioinspired Hydrophobic Cellulose Nanocrystal Composite Films as Organic-Solvent-Responsive Structural-Color Rewritable Papers.

Lots of beetles, moths, and birds in the natural world present stunning unique structural colors as well as excellent hydrophobic performances. Herein, a novel bioinspired variable structural-color film with organic-solvent responsiveness and surface hydrophobicity was fabricated. Cellulose nanocrystals (CNCs) provided structural color with left-handed helicity. PEG-PPG-PEG triblock copolymers (PPPTCs) were blended with CNCs, giving rise to the organic-solvent-responsive structural color and wider red-shift window of the reflectance peak. The color of the film could be regulated repeatedly under the stimulus of cyclohexanone with an obvious red shift up to 107 nm, corresponding to a macroscopic color change from blue to yellow. Low-surface-energy compound hexadecyltrimethoxysilane (HDTMS) was covalently grafted on the surface in a one-step method to introduce hydrophobicity, successfully preventing the effect of water on the ordered nanostructure. Based on the bionics principle, the as-prepared CNC/PPPTC nanocomposite films with variable structural colors and hydrophobicity are beneficial to their prospective applications in display screens, rewritable hydrophobic structural-color-changing paper, biomimetic sensors, and so forth.