Molecular Shell Research Articles

ATOMS: ALMA three-millimeter observations of massive star-forming regions – XVIII. On the origin and evolution of dense gas fragments in molecular shells of compact H ii regions

ATOMS: ALMA three-millimeter observations of massive star-forming regions – XVIII. On the origin and evolution of dense gas fragments in molecular shells of compact H <scp>ii</scp> regions

A structural determinant of the behavior of water at hydration and nanoconfinement conditions.

The molecular nature of the phases that conform the two-liquid scenario is elucidated in this work in the light of a molecular principle governing water structuring, which unveils the relevance of the contraction and reorientation of the second molecular shell to allow for the existence of coordination defects in water's hydrogen bond network. In turn, such principle is shown to also determine the behavior of hydration and nanoconfined water while enabling to define conditions for wettability (quantifying hydrophobicity and predicting drying transitions), thus opening the possibility to unravel the active role of water in central fields of research.

Taxonomic revision of two species in the genus Ptychorhynchus Simpson, 1900 (Bivalvia: Unionidae: Gonideinae), with description of a new species.

Accurate identification and precise classification of freshwater mussel species that are among the most threatened freshwater taxa in the world, play a crucial role in informing conservation and management efforts for these organisms. However, due to the variability in shell morphology, relying solely on shell characteristics for species taxonomy poses significant challenges, thereby impeding effective conservation planning and management. The freshwater mussel genus Ptychorhynchus Simpson, 1900 is one such group in need of study. We integrate molecular phylogeny, shell morphology and soft-body anatomy to examine the classification of Ptychorhynchus denserugata (Haas, 1910) and Ptychorhynchus resupinatus (von Martens, 1902). The COI barcoding data support the clustering of P. denserugata and Nodularia douglasiae within a single clade, and P. denserugata shares the diagnostic feature of the genus Nodularia , i.e. knobs or bumps on the inner mantle surface in the excurrent aperture. Therefore, by integrating molecular data and anatomical characteristics, we confirm that the nominal species P. denserugata syn. nov. is a new synonym for N. douglasiae . The multi-locus (COI + ND1 + 16S rRNA + 18S rRNA + 28S rRNA ) phylogeny and mitochondrial phylogenomics support the transfer of P. resupinatus from Ptychorhynchus to the newly elevated genus Cosmopseudodon stat. rev., as Cosmopseudodon resupinatus stat. rev. that is still considered the designated type species. We also describe a new species based on integrative taxonomy, i.e. Cosmopseudodon wenshanensis sp. nov. The comprehensive understanding of the taxonomy and diversity of the revised Cosmopseudodon species, and shell heteromorphism of N. douglasiae (=P. denserugata syn. nov.), will serve as a crucial foundation for further scientific assessment and conservation strategies pertaining to these taxa. ZooBank: urn:lsid:zoobank.org:pub:E48968B1-DF0F-42AD-8F31-B8C95F23CE57.

Enhancement in Anticancer Activity of Chitosan Tailored Imidazole-2-Thiosemicarbazones against MCF-7 Cancer Cell Line by Coordination with Copper(II) Ions

The coordination behavior of new batch synthesized chitosan imidazole-2-thiosemicarbazones tailored from both the low molecular weight commercial chitosan and high molecular weight crab shell chitosan was confirmed by Fourier Transform Infrared (FT-IR) and magnetic susceptibility measurements. Chlorine content in the complexes was estimated by potentiometric titration technique. The study showed the tridentate NNS tridentate coordination with copper (II) ion in a square planar orientation with the remaining valence satisfied by coordination with chloride ion. The MTT assay studies showed an enhancement in the anticancer activity of these chitosan thiosemicarbazone ligands upon their coordination with copper (II) ions against the human breast cancer (MCF-7) cell line in vitro. The minimal cytotoxicity of both the ligands and complexes against the normal mouse embryonic fibroblast (NIH3T3) cells revealed the selective attraction of these biomaterial chitosan derivatives towards the cancer cells with non-toxicity to healthy cells. There was only a marginal effect of molecular weight (Mw) and degree of deacetylation (DDA) of chitosan upon the anticancer activity of these chitosan derivatives.

PROJECT-J: JWST Observations of HH46 IRS and Its Outflow. Overview and First Results

We present the first results of the JWST program PROJECT-J (PROtostellar JEts Cradle Tested with JWST), designed to study the Class I source HH46 IRS and its outflow through NIRSpec and MIRI spectroscopy (1.66–28 μm). The data provide line images (∼6.″6 in length with NIRSpec, and up to ∼20″ with MIRI) revealing unprecedented details within the jet, the molecular outflow, and the cavity. We detect, for the first time, the redshifted jet within ∼90 au from the source. Dozens of shock-excited forbidden lines are observed, including highly ionized species such as [Ne iii] 15.5 μm, suggesting that the gas is excited by high velocity (>80 km s−1) shocks in a relatively high-density medium. Images of H2 lines at different excitations outline a complex molecular flow, where a bright cavity, molecular shells, and a jet-driven bow shock interact with and are shaped by the ambient conditions. Additional NIRCam 2 μm images resolve the HH46 IRS ∼110 au binary system and suggest that the large asymmetries observed between the jet and the H2 wide-angle emission could be due to two separate outflows being driven by the two sources. The spectra of the unresolved binary show deep ice bands and plenty of gaseous lines in absorption, likely originating in a cold envelope or disk. In conclusion, JWST has unraveled for the first time the origin of the HH46 IRS complex outflow demonstrating its capability to investigate embedded regions around young stars, which remain elusive even at near-IR wavelengths.

Introducing hafnium to atomically small- and medium-sized tin clusters (HfSnn0/-/2- (n = 4–17)): A computational investigation of geometrical and growth behavior, spectral properties, electronic configuration and thermochemistry

The global and local minimum configurations of single Hf atom doped Sn clusters are conducted via density function theory (DFT) combined with artificial bee colony algorithm (ABCluster). Furthermore, DFT method is also used to systematically investigate on their structural growth evolution, spectral and electronic information, thermochemical properties following the size of tin clusters doped Hf atom. Structurally, the ground-state geometries of neutral, anion and di-anion are discovered that, from n = 4, the number of Sn atoms in cluster, HfSnn0/-/2- adsorb additional Sn atom on the prior architecture one by one until forming n = 17 for HfSnn-10/-, as well as forming n = 16 for HfSnn-12-. And for the HfSn110/- and HfSn102- as beginning the species veritably develop sealed architectures. The strongest vibrational modes of sealed nanoclusters are stretching modes of Hf atom with infrared actives and breathing modes of the Sn cage framework with Raman actives, respectively. The natural population analysis (NPA) elucidates the stronger relationship between the Hf atoms and the tin frameworks in sealed clusters than that in unsealed clusters. The results of thermochemical properties, molecular orbital shell (MOs), adaptive natural density partitioning (AdNDP) and ultraviolet visible absorption spectrum (UV–Vis) indicate that, the HfSn16 with high symmetry of Td exhibits thermochemical stability and optoelectronic properties, which is utilized potentially as zero-dimensional unit of self-assembling fluorescent nanomaterials.

Theoretical Study of Strong Coupling between Molecular Shells and Chiral Plasmons of Gold Nanoparticles Helices.

Chiral plasmonic nanostructures can produce strong chiral optical responses and have potential applications in photonics. Experimentally, metallic nanoparticle helices have been synthesized to achieve strong chiral responses. Strong coupling effects between the quantum emitters and the plasmon have attracted significant attention in the past decade and have been recently extended to the chiral plasmon of nanostructures. However, the strong coupling between molecules and metallic nanosphere helices has not been reported yet. In this article we study theoretically such an effect and examine the modulation of chiral and coupling effects by illumination light and molecular layer thickness. Our study may guide further experimental studies.

Discovery of an old supernova remnant candidate through carbon monoxide line emission

Most old supernova remnants (SNRs) in the Milky Way have not yet been identified. Considering their high potential number and the sufficient momentum-energy transfer to the interstellar medium (ISM), they are a key part of our understanding of the overall role of SNRs in the ISM. Here, we report our discovery of an expanding molecular shell identified by CO line observations, namely It covers a known SNR, specifically G16.0$-$0.5, and is larger in size (i.e.,\ 0.56$^ over 0.20$^ Based on its spatial and kinematic structures, weak nonthermal radio-continuum emission, and derived physical properties, we suggest that it is an old SNR. At a systemic velocity of +41.3 the best estimated kinematic distance of is sim 3.2 kpc, implying its radius of about 15.6 pc. The age of is estimated to be greater than sim $ yr, and, in a dense molecular environment, it has formed dense and thin shell layers. The kinetic energy of the expanding molecular gas of is about $6.4 $ erg, accounting for approximately six percent of the initial SN explosion energy. Although old SNRs have essentially become cold and hard to detect, our discovery suggests that they can be found by searching for CO line emissions.

Novel Approach to the Synthesis of Bithiophenesilane Dendrimers with Efficient Intramolecular Energy Transfer

A synthetic scheme allowing the preparation of nanostructured organosilicon luminophores of branched or dendritic structure with up to 18 bithiophenesilane donor fragments and one central acceptor fragment has been elaborated. This universal scheme has been successfully upscaled to 20 g of the product, and its efficiency has been verified by the synthesis of two earlier unknown bithiophenesilane dendrimers with dense molecular shell and the central acceptor fragment, 1,4-bis(5-phenylthienyl-2-yl)benzene. The synthesis of more branched dendrimers under the Suzuki reaction conditions has led to the formation of the side products with the rupture of the Si–C(thiophene) bond, not typical of the synthesis of analogous compounds with lower branching degree under the same conditions.

Dual pH- and temperature-responsive poly(dimethylaminoethyl methacrylate)-coated mesoporous silica nanoparticles as a smart drug delivery system

A robust drug delivery system was created by grafting poly(dimethylaminoethyl methacrylate) (PDMAEMA) onto silica nanoparticles with two different lengths using an in situ atom transfer radical polymerization, resulting in the formation of a pH- and temperature-sensitive shell. The high molecular weight PDMAEMA demonstrated effective controlled drug release, and prevented drug release in healthy cells. Drug release occurred through polymer shell protonation at pH 5. The critical temperature of 41 °C facilitated rapid solvation of the shell polymers in the blood, preventing tissue accumulation and reducing toxicity compared to systems with lower critical solution temperatures. Field-emission scanning electron microscopy analysis and nitrogen adsorption/desorption analysis showed that the nanoparticles have a fine network, mesoporous structure, and a mean size of around 17 nm that show their excellent capacity for loading drugs. Fourier-transform infrared spectroscopy showed that all the modification steps and polymerization were successfully implemented. Thermogravimetric analysis showed PDMAEMA chains with two different lengths grafted onto the nanoparticles. Transmission electron microscopy analysis also showed grafted polymer chains on the hybrid nanoparticles. The release profile of model cancer drugs (doxorubicin and methotrexate) varied with pH and temperature, with high molecular weight PDMAEMA shells effectively preventing drug release at neutral pH. In vitro analysis using the HeLa cell line showed minimal toxicity in blank samples and significant release profile in acidic environment.

One, Two, Three ... An Explosive Outflow in IRAS 12326-6245 Revealed by ALMA

In the last years there has been a substantial increase in the number of the reported massive and luminous star-forming regions with related explosive outflows thanks to the superb sensitivity and angular resolution provided by the new radio, infrared, and optical facilities. Here, we report one more explosive outflow related with the massive and bright star-forming region IRAS 12326−6245 using Band 6 sensitive and high-angular-resolution (∼0.″2) Atacama Large Millimeter/Submillimeter Array observations. We find over 10 molecular and collimated well-defined streamers, with Hubble–Lemaitre–like expansion motions, and pointing right to the center of a dusty and molecular shell (reported for the first time here) localized in the northern part of the UC H ii region known as G301.1A. The estimated kinematic age and energy for the explosion are ∼700 yr and 1048 erg, respectively. Taking into account the recently reported explosive outflows together with IRAS 12326−6245, we estimate an event rate of once every 90 yr in our Galaxy, similar to the formation rate of massive stars.

Probabilistic Constellation Shaping for Molecular Communications

Molecular communication (MC) is an emerging field aiming at realizing information exchange via chemical signals between nanomachines in nanonetworks. Information transmission that is energy-efficient and relies on relatively low-complexity transceiver techniques is of practical importance for MC systems. Based on the fact that constellation shaping can improve energy efficiency, in this paper, we propose a molecular shell mapping (MSM) scheme to implement the probabilistic constellation shaping for MC. The MSM method is designed to exploit the concentration sequences with the lowest sum sequence weight, which results in an energy-efficient signal constellation. Furthermore, we propose an algorithm for selecting and sorting the concentration sequences to mitigate inter-symbol interference. For information detection, we design a genie-aided maximum-likelihood (ML) detector and a realistic ML detector to leverage the constructive effect of intra-sequence interference, as well as derive their bit error rates and achievable rates. Additionally, for the applications using large blocklength sequences, a low-complexity ML detection method is proposed. Numerical simulation results confirm that the shaped signaling using the MSM method is more energy-efficient than the conventional equiprobable signaling, achieving shaping gains of up to 1.5 dB at an ultra-short blocklength of 4.

Delayed electron emission in photomultiplier tubes

The time distributions of pulses generated by noise or external light sources in the ХР2020, ХР2232В, ХР1021, FEU-85, FEU-87, FEU-93, FEU-130, and R7600U-200 photomultiplier tubes (PMTs) were investigated using an autocorrelation delayed-coincidence time spectrometer. The observed pulse time correlations were of two types: non-exponential, related to the detection of the effects of feedback ions; and exponential, caused by the interaction of secondary-emission electrons with the PMT dynodes. Detection of multi-electron events arising from the action of external radiators leads to intensification of residual-gas ionization processes in the PMT. However, no analogy is observed in the shapes of the feedback ion spectra for different types of PMT despite the identical composition of photocathodes or dynodes. This might be related to differences in PMT manufacturing processes and to possible different restructuring of molecular electron shells in the photocathode material constituents. The detection of single-electron events (noise pulses) in some of the PMTs studied was not always characterized by nanosecond-scale emissions that might be expected to result from metastable states related to properties of their photocathodes and dynodes, and on the material processing technology used in PMT manufacture. It is difficult to describe exactly the mechanisms leading to delayed electron emission. The source of such events remains open to attempts at explanation and further research.

Disulfide-Bridged Dendritic Organosilicas-Based Biodegradable Molecularly Imprinted Polymers for Multiple Targeting and pH/Redox-Responsive Drug Release toward Chemical/Photodynamic Synergistic Tumor Therapy.

In this study, a sialic acid (SA) and transferrin (TF) imprinted biodegradable disulfide bridging organosilicas-based drug delivery system (SS-DMONS/DOX-Ce6@MIPs) for targeted cancer therapy is constructed, for the first time. Disulfide bridged dendritic mesoporous organosilicas nanoparticles (SS-DMONs) not only enhance drug loading as the drug repository, but also provide enough specific surface area for the molecular imprinting shell to expose more degradation and imprinted sites on the surface. In addition, SS can be disturbed in a highly reducing tumor microenvironment to achieve degradation. The biodegradable imprinting film, prepared with customized 2-amino-N-(3,4-dihydroxyphenethyl)-3-mercaptopropanamide and 4-mercaptophenylboronic acid as functional monomers, endows SS-DMONs with active targeting capacity, and responsive drug release through degradation under acidic and highly reductive tumor microenvironment. SS-DMONS/DOX-Ce6@MIPs after binding of TF can target tumor cells actively through multiple interactions, including the affinity between antigen and antibody, and the specific recognition between molecularly imprinted polymers and template molecules. Under laser irradiation the loaded chlorin e6 (Ce6) that can produce toxic reactive oxygen, combined with the doxorubicin (DOX), achieves chemical/photodynamic synergistic anticancer effects. SS-DMONS/DOX-Ce6@MIPs present excellent tumor targeting and dual-responsive drug release, which provides an effective strategy for chemical/photodynamic antitumor therapy.

Quantum-Chemical and Experimental Study on the Interactions between the Magnetic Core and the Molecular Shell of Cobalt Ferrite Nanoparticles in Aqueous Suspensions

This article is focused on the theoretical and experimental study of the interactions between the perchlorate anions and the cations of cobalt ferrite magnetic nanoparticles prepared by a co-precipitation method. The magnetic nanoparticles with surface modified using perchloric acid were stabilized in aqueous dispersion based upon the predominant electric repulsive forces between the coated nanoparticles, balancing the magnetic dipole-dipole attraction. Quantum chemical modeling has revealed the physical-chemical properties of perchlorate anion (electric charges, dipole moment, and energies of frontier orbitals) that suggests the ability to interact with both nanoparticle metal cations and surrounding water molecules. Microstructural investigations by scanning electron microscopy, X-ray diffractometry, and vibrating sample magnetometry revealed crystallinity and granulation of the suspended ferrophase, thus confirming the adequate surface coating with perchlorate anions. The nanotoxicity study, carried out on agricultural plantlets in early ontogenetic stages has revealed differences in the photosynthesis pigment concentrations induced by the magnetic nanoparticle supply.

Sequential release of vascular endothelial growth factor-A and bone morphogenetic protein-2 from osteogenic scaffolds assembled by PLGA microcapsules: A preliminary study in vitro

Bone regeneration is a complex process sequentially regulated by multiple cytokines at different stages. Vascular endothelial growth factor-A (VEGF-A) and bone morphogenetic protein-2 (BMP-2) are the two most important factors involved in this process, and the combination of the two can achieve better bone regeneration by coupling angiogenesis and osteogenesis. In this study, poly(lactic-co-glycolic acid) (PLGA) microspheres with core-shell structure (microcapsules) encapsulating VEGF-A or BMP-2 were prepared by coaxial channel injection and continuous fluid technology. The sequential release of two cytokines by microcapsules with different PLGA molecular weight and shell thickness and its performance in vitro were explored. It was demonstrated that the molecular weight of PLGA significantly affected the degradation and release kinetics of microcapsules, while the thickness of the shell can regulate the release in a finer level. VEGF-A encapsulated microcapsules with low molecular weight can induce vascular endothelial cells to form lumens structures in vitro at an early stage. And BMP-2 encapsulated microcapsules could promote osteogenic differentiation, but the effect could be delayed when the microcapsules were prepared with PLGA of 150 kDa. In conclusion, the core-shell PLGA microcapsules in this study can sequentially release VEGF-A and BMP-2 at different stages to simulate natural bone repair.

The effect of winds on atmospheric layers of red supergiants

Context. Red supergiants (RSGs) are evolved massive stars in a stage preceding core-collapse supernova. The physical processes that trigger mass loss in their atmospheres are still not fully understood, and they remain one of the key questions in stellar astrophysics. Based on observations of α Ori, a new semi-empirical method to add a wind to hydrostatic model atmospheres of RSGs was recently developed. This method can reproduce many of the static molecular shell (or ‘MOLsphere’) spectral features. Aims. We used this method of adding a semi-empirical wind to a MARCS model atmosphere to compute synthetic observables, comparing the model to spatially resolved interferometric observations. We present a case study to model published interferometric data of HD 95687 and V602 Car obtained with the AMBER instrument at the Very Large Telescope Interferometer (VLTI). Methods. We computed model intensities with respect to the line-of-sight angle (µ) for different mass-loss rates, spectra, and visibilities using the radiative transfer code TURBOSPECTRUM. We were able to convolve the models to match the different spectral resolutions of the VLTI instruments, studying a wavelength range of 1.8–5 µm corresponding to the K, L, and M bands for GRAVITY and MATISSE data. The model spectra and squared visibility amplitudes were compared with the published VLTI/AMBER data. Results. The synthetic visibilities reproduce observed drops in the CO, SiO, and water layers that are not shown in visibilities based on MARCS models alone. For the case studies, we find that adding a wind onto the MARCS model with simple radiative equilibrium dramatically improves the agreement with the squared visibility amplitudes as well as the spectra, with the fit being even better when applying a steeper density profile than predicted from previous studies. Our results reproduce observed extended atmospheres up to several stellar radii. Conclusions. This paper shows the potential of our model to describe extended atmospheres in RSGs. It can reproduce the shapes of the spectra and visibilities with a better accuracy in the CO and water lines than previous models. The method can be extended to other wavelength bands for both spectroscopic and interferometric observations. We provide temperature and density stratifications that succeed, for the first time, in reproducing observed interferometric properties of RSG atmospheres.

The Cassiopeia Filament: A Blown Spur of the Local Arm

We present wide-field and high-sensitivity CO(1–0) molecular line observations toward the Cassiopeia region, using the 13.7 m millimeter telescope of the Purple Mountain Observatory. The CO observations reveal a large-scale highly filamentary molecular cloud within the Galactic region of 132.°0 ≥ l ≥ 122.°0 and −1.°0 ≤ b ≤ 3.°0 and the velocity range from approximately +1 to +4 km s−1. The measured length of the large-scale filament, referred to as the Cassiopeia Filament, is ∼390 pc. The observed properties of the Cassiopeia Filament, such as length, column density, and velocity gradient, are consistent with those synthetic large-scale filaments in the inter-arm regions. Based on its observed properties and location on the Galactic plane, we suggest that the Cassiopeia Filament is a spur of the Local arm, which is formed due to the galactic shear. The western end of the Cassiopeia Filament shows a giant arc-like molecular gas shell, which extends in the velocity range from roughly −1 to +7 km s−1. Finger-like structures, with systematic velocity gradients, are detected in the shell. The CO kinematics suggest that the large shell is expanding at a velocity of ∼6.5 km s−1. Both the shell and finger-like structures outline a giant bubble with a radius of ∼16 pc, which is likely produced by the stellar wind from the progenitor star of a supernova remnant. The observed spectral line widths suggest that the whole Cassiopeia Filament was quiescent initially until its west part was blown by the stellar wind and became supersonically turbulent.

Short-Range Cooperative Slow-down of Water Solvation Dynamics Around SO4 2--Mg2+ Ion Pairs.

The presence of ions affects the structure and dynamics of water on a multitude of length and time scales. In this context, pairs of Mg2+ and SO4 2- ions in water constitute a prototypical system for which conflicting pictures of hydration geometries and dynamics have been reported. Key issues are the molecular pair and solvation shell geometries, the spatial range of electric interactions, and their impact on solvation dynamics. Here, we introduce asymmetric SO4 2- stretching vibrations as new and most specific local probes of solvation dynamics that allow to access ion hydration dynamics at the dilute concentration (0.2 M) of a native electrolyte environment. Highly sensitive heterodyne 2D-IR spectroscopy in the fingerprint region of the SO4 2- ions around 1100 cm-1 reveals a specific slow-down of solvation dynamics for hydrated MgSO4 and for Na2SO4 in the presence of Mg2+ ions, which manifests as a retardation of spectral diffusion compared to aqueous Na2SO4 solutions in the absence of Mg2+ ions. Extensive molecular dynamics and density functional theory QM/MM simulations provide a microscopic view of the observed ultrafast dephasing and hydration dynamics. They suggest a molecular picture where the slow-down of hydration dynamics arises from the structural peculiarities of solvent-shared SO4 2--Mg2+ ion pairs.

Locating dust and molecules in the inner circumstellar environment of R Sculptoris with MATISSE

Context. Asymptotic giant branch (AGB) stars are one of the main sources of dust production in the Galaxy. However, it is not yet clear what this process looks like and where the dust happens to be condensing in the circumstellar environment. Aims. By characterizing the location of the dust and the molecules in the close environment of an AGB star, we aim to achieve a better understanding the history of the dust formation process. Methods. We observed the carbon star R Scl with the thermal-infrared VLTI/MATISSE instrument in L- and N-bands. The high angular resolution of the VLTI observations (as small as 4.4 mas in the L-band and 15 mas in the N-band with ATs), combined with a large uv-plane coverage allowed us to use image reconstruction methods. To constrain the dust and molecules’ location, we used two different methods: one using MIRA image reconstruction algorithm and the second using the 1D code RHAPSODY. Results. We found evidence of C2H2 and HCN molecules between 1 and 3.4 R* which is much closer to the star than the location of the dust (between 3.8 and 17.0 R*). We also estimated a mass-loss rate of 1.2 ± 0.4 × 10−6 M⊙ yr−1. In the meantime, we confirmed the previously published characteristics of a thin dust shell, composed of amorphous carbon (amC) and silicon carbide (SiC). However, no clear SiC feature has been detected in the MATISSE visibilities. This might be caused by molecular absorption that can affect the shape of the SiC band at 11.3 µm. Conclusions. The appearance of the molecular shells is in good agreement with predictions from dynamical atmosphere models. For the first time, we co-located dust and molecules in the environment of an AGB star. We confirm that the molecules are located closer to the star than the dust. The MIRA images unveil the presence of a clumpy environment in the fuzzy emission region beyond 4.0 R*. Furthermore, with the available dynamic range and angular resolution, we did not detect the presence of a binary companion. To solve this problem, additional observations combining MATISSE and SAM-VISIR instrument should enable this detection in future studies.