Strong Hotspots Research Articles

Increased electric field enhancement and broad wavelength tunability by plasmonic bow-tie nano-antenna based on fractal geometry with grid

We propose and analyze a new type of plasmonic bow-tie nano-antenna based on fractal geometry with grid. The optical properties of the first-, second- and third-iteration of the proposed fractal nano-antennas including absorption spectra, gap enhancement, electric field distribution and charge density are numerically investigated by means of finite-difference time-domain (FDTD) method. We demonstrate the bonding and anti-bonding modes arising from the plasmon hybridization modes of the proposed fractal nano-antennas. Our simulation results show that these nano-antennas can be tuned by changing the refractive index of the surrounding medium or antenna thickness. We also observe a strong electric field hotspot inside the gap region as the fractal iteration increases. Accordingly, the gap enhancement of the third-iteration is achieved up to 144.5 v/m within the nano-antenna gap. We find that the proposed second- and third-iteration bow-tie fractal nano-antennas are good candidates for strong electric field localization and tunable broadband applications.

Impact of Propagative Surface Plasmon Polaritons on the Electromagnetic Enhancement by Localized Gap Surface Plasmons Between Metallic Nanoparticles and Substrate

The nanoparticle-on-mirror system as a surface-enhanced Raman scattering substrate is sufficient for single molecule detection and possesses advantages of high reproducibility and ease of assembly. In this paper, one single spherical gold nanoparticle (NP) placed on a flat gold substrate with a gap size of 10 nm is firstly studied. Then, two NPs with separations in order of wavelengths is investigated. The enhanced field of the localized gap surface plasmon (LGSP) in the NP-substrate nanogap is analyzed quantitatively with the finite element method, and a simplified model is proposed to describe the impact of the propagative surface plasmon polariton (SPP) on the LGSP. A 34% improvement of the enhancement factor of the Raman signal is achieved compared to a single NP. The field distribution of SPPs is found to play an important role in determining the optimal positions of NPs to generate the strongest hot spots. Then, the case of a single NP or a NP doublet in a gold groove is considered, and an 8.22-fold increase of the enhancement factor of the Raman signal is obtained compared to the case without the groove. The interference among the groove-excited SPPs, the NP-excited SPPs, and the LGSP determines the optimal positions of the NPs in the groove to generate the strongest hot spots. The present work reveals the great impact of the propagative SPPs on the field enhancement of the LGSP in the NP-substrate gap, and provides a theoretical basis for generating multiple strong hot spots by arranging NPs’ positions according to the field distribution of the propagative SPPs.

Bioinspired ZnS:Gd Nanoparticles Synthesized from an Endophytic Fungi Aspergillus flavus for Fluorescence-Based Metal Detection.

Recently, several nonconventional sources have emerged as strong hotspots for the biosynthesis of chalcogenide quantum dots. However, studies that have ascertained the biomimetic methodologies that initiate biosynthesis are rather limited. The present investigation portrays a few perspectives of rare-earth(Gd)-doped ZnS biosynthesis using the endophytic fungi Aspergillus flavus for sensing metals based on their fluorescence. Analysis of ZnS:Gd nanoparticles was performed by elemental analysis, energy-dispersive X-ray spectroscopy (EDS), atomic force microscopy (AFM), X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), photoluminescence (PL), and transmission electron microscopy (TEM). The results of TEM demonstrated that the particles were polycrystalline in nature, with a mean size of 10–18 nm. The fluorescence amenability of the biogenic ZnS nanoparticles was further used for the development of a simple and efficient sensing array. The results showed sensitive and detectable quenching/enhancement in the fluorescence of biogenic colloidal ZnS nanoparticles, in the presence of Pb (II), Cd (II), Hg (II), Cu (II) and Ni (II), respectively. The fluorescence intensity of the biogenic ZnS:Gd nanoparticles was found to increase compared to that of the ZnS nanoparticles that capacitate these systems as a reliable fluorescence sensing platform with selective environmental applications.

Interplay Between Near-Field Properties and Au Nanorod Cluster Structure: Extending Hot Spots for Surface-Enhanced Raman Scattering

Materials science has observed a continuous increase in the use of metal nanoparticles in a wide range of studies, from fundamental physics to technological applications such as photocatalysis and optical communication devices. This broad scope has the same fundamental origin, the localized surface plasmons, whose excitation leads to strong light confinement, especially in the vicinity of closely spaced nanoparticles, the hot spots. The field amplification may be used to amplify the Raman scattering of adsorbed molecules, which is known as surface-enhanced Raman scattering (SERS). A crucial and limiting characteristic of SERS hot spots is their very localized nature, that influences the SERS intensity reproducibility as well as the probabilities of observation of single-molecule SERS signals. In this paper we discuss the correlation between SERS performance and gold nanorod cluster structures using transmission electron microscopy, SERS spectra and numerical simulations. The experimental data showed interesting behavior for the combination of end-to-end and side-by-side interactions, revealing the possibility of creating strong hot spots with a more extended spatial distribution. The results give insights into the development of high-performance SERS substrates.

Elevated pyrimidine dimer formation at distinct genomic bases underlies promoter mutation hotspots in UV-exposed cancers.

Sequencing of whole cancer genomes has revealed an abundance of recurrent mutations in gene-regulatory promoter regions, in particular in melanoma where strong mutation hotspots are observed adjacent to ETS-family transcription factor (TF) binding sites. While sometimes interpreted as functional driver events, these mutations are commonly believed to be due to locally inhibited DNA repair. Here, we first show that low-dose UV light induces mutations preferably at a known ETS promoter hotspot in cultured cells even in the absence of global or transcription-coupled nucleotide excision repair (NER). Further, by genome-wide mapping of cyclobutane pyrimidine dimers (CPDs) shortly after UV exposure and thus before DNA repair, we find that ETS-related mutation hotspots exhibit strong increases in CPD formation efficacy in a manner consistent with tumor mutation data at the single-base level. Analysis of a large whole genome cohort illustrates the widespread contribution of this effect to recurrent mutations in melanoma. While inhibited NER underlies a general increase in somatic mutation burden in regulatory elements including ETS sites, our data supports that elevated DNA damage formation at specific genomic bases is at the core of the prominent promoter mutation hotspots seen in skin cancers, thus explaining a key phenomenon in whole-genome cancer analyses.

Integrated optofluidic micro-pumps in micro-channels with uniform excitation of a polarization rotating beam.

We report an integrated optofluidic micro-pump with a pair of mirrored stirrers of circulating micro-beads in a micro-channel, driven by plasmon-assisted optical manipulation with the excitation of a polarization rotating beam. H-shaped apertures (HSAs) on a gold surface produce strong near-field hot spots when they are illuminated with a light beam polarized parallel to the long axis of "H." With the rotating of excitation polarization, loops of HSAs with gradually varied orientations can produce the circulation of hot spots, which can further trap micro-beads and make them go around in circles. A different sequence of HSAs can produce a different direction and phase of bead rotation, even under uniform excitation. A pair of mirrored circulations of micro-beads in a micro-channel can induce very effective directional flow. Through numerical modeling, we find that a group of non-synchronized multi-phase mirrored circulations can produce a very uniform flow rate with a speed of more than 10 micrometers per second. These micro-pumps can be heavily integrated and activated by a single beam, while the flow direction of each pump can be regulated, even under a uniform excitation. Our design proposes a new approach for the flow pumping in micro- and nanofluidic devices.

Proteogenomic characterization and comprehensive integrative genomic analysis of human colorectal cancer liver metastasis

BackgroundProteogenomic characterization and integrative and comparative genomic analysis provide a functional context to annotate genomic abnormalities with prognostic value.MethodsHere, we analyzed the proteomes and performed whole exome and transcriptome sequencing and single nucleotide polymorphism array profiling for 2 sets of triplet samples comprised of normal colorectal tissue, primary CRC tissue, and synchronous matched liver metastatic tissue.ResultsWe identified 112 CNV-mRNA-protein correlated molecules, including up-regulated COL1A2 and BGN associated with prognosis, and four strongest hot spots (chromosomes X, 7, 16 and 1) driving global mRNA abundance variation in CRC liver metastasis. Two sites (DMRTB1R202H and PARP4V458I) were revealed to frequent mutate only in the liver metastatic cohort and displayed dysregulated protein abundance. Moreover, we confirmed that the mutated peptide number has potential prognosis value and somatic variants displayed increased protein abundance, including high MYH9 and CCT6A expression, with clinical significance.ConclusionsOur proteogenomic characterization and integrative and comparative genomic analysis provides a new paradigm for understanding human colon and rectal cancer liver metastasis.Trial registrationClinicalTrials, NCT02917707. Registered 28 September 2016, https://clinicaltrials.gov/ct2/show/NCT02917707.

Target-Triggered Catalytic Hairpin Assembly-Induced Core-Satellite Nanostructures for High-Sensitive "Off-to-On" SERS Detection of Intracellular MicroRNA.

Surface-enhanced Raman scattering (SERS) technology is emerging as a powerful molecules detection method with distinct advantages of high stability, good specificity, and low background signal compared with current prevailing fluorescence technique. However, the relative low sensitivity of SERS limits its wide applications. Engineered metallic nanoparticle aggregates with strong electromagnetic hot spots are urgently needed for low abundant molecules SERS detection. Herein, a microRNA (miRNA)-triggered catalytic hairpin assembly (CHA)-induced core-satellite (CS) nanostructure with multiple hot spots and strong electromagnetic field in nanogaps is designed. The unique plasmonic CS nanostructure is constructed by plasmonic Au nanodumbbells (Au NDs) as core and Au nanoparticles (Au NPs) as satellites, and it possesses enhanced electromagnetic field compared to that of Au NPs-Au nanorods (Au NRs) CS and Au NPs only. The "off-to-on" SERS strategy leads to a wide linear miRNA detection range from 10-19 to 10-9 M with a limit of detection (LOD) down to 0.85 aM in vitro. Intracellular accurate and sensitive miRNAs SERS imaging detection in different cell lines with distinct different miRNA expression levels are also achieved. The proposed SERS platform contributes to engineering metallic nanoparticle aggregates with strong electromagnetic intensity and has potential application in quantitative and precise detection significant intracellular molecules.

(Invited) The Mechanisms of Hot-Electron Generation in Plasmonic and Hybrid Nanomaterials: Comparing Different Material Systems and Geometries

Generation of energetic (hot) electrons is an intrinsic property of any plasmonic nanostructure under illumination. Simultaneously, a striking advantage of metal nanocrystals over semiconductors lies in their very large absorption cross sections. Therefore, metal nanostructures with strong and tailored plasmonic resonances are very attractive for photocatalytic applications in which excited electrons play an important role. However, the central questions in the problem of plasmonic hot electrons are the number of optically excited energetic electrons in a nanocrystal and how to extract such electrons. Here we develop a theory describing the generation rates and the energy distributions of hot electrons in nanocrystals with various geometries [1-4]. In particular, we show that nanostructures with strong and extended plasmonic hot spots generate unusually large numbers of energetic electrons, which can be observed using the ultra-fast transient spectroscopy [2,4,5] as well as photochemistry. Hot-electron generation together with non-radiative plasmonic transfer [6] represent efficient methods to transfer and localize optical and photo-chemical energies. A.O. Govorov, H. Zhang, V. Demir, and Y. K. Gun’ko, Nano Today, 9, 85 (2014).H. Harutyunyan, A. B. F. Martinson, D. Rosenmann, L.K. Khorashad, L.V.Besteiro, A.O.Govorov, and G.P. Wiederrecht, Nature Nanotechnology 10, 770–774 (2015).L.V. Besteiro, X.-T. Kong, Z. Wang, G. V. Hartland, A.O. Govorov, ACS Photonics, DOI: 10.1021/acsphotonics.7b00751 (2017).M.E. Sykes, J. W. Stewart, G. M. Akselrod, X.-T. Kong, Z. Wang, D. J. Gosztola, A.B.F. Martinson, D. Rosenmann, M. H. Mikkelsen, A. O. Govorov, G. P. Wiederrecht, Nature Communications, 8, 986 (2017). G.V. Hartland, L. Besteiro, P. Johns, A. O. Govorov, What’s so Hot about Electrons in Metal Nanoparticles? (perspective paper), ACS Energy Letters, 2, 1641–1653 (2017).E.-M. Roller, L.V. Besteiro, C. Pupp, L. Khosravi Khorashad, A. O. Govorov, T.Liedl, Nature Physics, 13, 761-765 (2017).

(Invited) Hot-Electron Generation and Energy Transfer in Plasmonic Nanostructures with Hot Spots: Quantum and Classical Mechanisms

Generation of energetic (hot) electrons is an intrinsic property of any plasmonic nanostructure under illumination. Simultaneously, a striking advantage of metal nanocrystals over semiconductors lies in their very large absorption cross sections. Therefore, metal nanostructures with strong and tailored plasmonic resonances are very attractive for photocatalytic applications in which excited electrons play an important role. However, the central questions in the problem of plasmonic hot electrons are the number of optically excited energetic electrons in a nanocrystal and how to extract such electrons. Here we develop a theory describing the generation rates and the energy distributions of hot electrons in nanocrystals with various geometries [1-4]. In particular, we show that nanostructures with strong and extended plasmonic hot spots generate unusually large numbers of energetic electrons, which can be observed using the ultra-fast transient spectroscopy [2,4] as well as photochemistry. Hot-electron generation together with non-radiative plasmonic transfer [5] represent efficient methods to transfer and localize optical and photo-chemical energies. A.O. Govorov, H. Zhang, V. Demi, and Y. K. Gun’ko, Nano Today, 9, 85 (2014).H. Harutyunyan, A. B. F. Martinson, D. Rosenmann, L.K. Khorashad, L.V.Besteiro, A.O.Govorov, and G.P. Wiederrecht, Nature Nanotechnology 10, 770–774 (2015).L.V. Besteiro, X.-T. Kong, Z. Wang, G. V. Hartland, A.O. Govorov, ACS Photonics, DOI: 10.1021/acsphotonics.7b00751 (2017).M.E. Sykes, J. W. Stewart, G. M. Akselrod, X.-T. Kong, Z. Wang, D. J. Gosztola, A.B.F. Martinson, D. Rosenmann, M. H. Mikkelsen, A. O. Govorov, G. P. Wiederrecht, Nature Communications, 8, 986 (2017).E.-M. Roller, L.V. Besteiro, C. Pupp, L. Khosravi Khorashad, A. O. Govorov, T.Liedl, Nature Physics, 13, 761-765 (2017).

Exploring the structural origins of cryptic sites on proteins

Molecular dynamics (MD) simulations of proteins reveal the existence of many transient surface pockets; however, the factors determining what small subset of these represent druggable or functionally relevant ligand binding sites, called "cryptic sites," are not understood. Here, we examine multiple X-ray structures for a set of proteins with validated cryptic sites, using the computational hot spot identification tool FTMap. The results show that cryptic sites in ligand-free structures generally have a strong binding energy hot spot very close by. As expected, regions around cryptic sites exhibit above-average flexibility, and close to 50% of the proteins studied here have unbound structures that could accommodate the ligand without clashes. Nevertheless, the strong hot spot neighboring each cryptic site is almost always exploited by the bound ligand, suggesting that binding may frequently involve an induced fit component. We additionally evaluated the structural basis for cryptic site formation, by comparing unbound to bound structures. Cryptic sites are most frequently occluded in the unbound structure by intrusion of loops (22.5%), side chains (19.4%), or in some cases entire helices (5.4%), but motions that create sites that are too open can also eliminate pockets (19.4%). The flexibility of cryptic sites frequently leads to missing side chains or loops (12%) that are particularly evident in low resolution crystal structures. An interesting observation is that cryptic sites formed solely by the movement of side chains, or of backbone segments with fewer than five residues, result only in low affinity binding sites with limited use for drug discovery.

Preparation and Raman enhancement properties of gold nanostars

Gold nanostars (GNSs) have a series of sharp tips structures, which will produce strong hot spots and have great application potential in Raman enhancement. In this paper, muti-tip GNSs have been prepared experimentally, and the control techniques of their tip and size have been mastered. For the first time, a fast and efficient self-assembly technique without additives has been developed, and a series of Surface Enhanced Raman Scattering (SERS) substrates have been successfully prepared by using this technique. The effect of different GNSs density of substrates on SERS signal is further studied experimentally. The results show that the SERS signal is closely related to the density of particles in the substrate. The higher density of GNSs in the substrate, the more hot spots covered by the incident light plate, and the greater contribution to the SERS signal.

Optimally designed gold nanorattles with strong built-in hotspots and weak polarization dependence

Localized electromagnetic fields generated by interparticle plasmon coupling suffer greatly from nonreproducibility because they are extremely sensitive to the nanoparticle aggregation status and the incident polarization. Here, we synthesize gold nanorattles that exhibit inherent aggregation-insensitive hotspots due to the intraparticle core–shell plasmon coupling, and investigate the structural effect on the intraparticle coupling strength and its polarization dependence. Through optimizing the structural parameters, we successfully synthesize gold nanorattles with strong built-in hotspots and weak polarization dependence. These aggregation-insensitive and weakly polarization-dependent hotspots make the Raman enhancement from nanorattle aggregates show an unusual weak dependence on the particle aggregation status, which therefore affords the opportunity to fabricate uniform and reproducible surface enhanced Raman scattering substrates.

Spatial analysis of cutaneous leishmaniasis in an endemic area of Iran based on environmental factors.

Leishmaniasis is a parasitic disease caused by different species of protozoan parasites. Cutaneous leishmaniasis (CL) is still a great public health problem in Iran, especially in Isfahan Province. Distribution and abundance of vectors and reservoirs of this disease is affected by different factors such as climatic, socioeconomic and cultural. This study aimed to identify the hotspot areas for CL in Isfahan and assess the relations between the climatic and topographic factors with CL incidence using spatial analysis. We collected data on the total number of CL cases, population at risk, vegetation coverage, altitude and climatic data for each district of the province from 2011 to 2015. Global Moran's Index was used to map clustering of CL cases across districts and the Getis-Ord (Gi*) statistics was used to determine hotspots areas of the disease in Isfahan. We applied overlay analysis to assess the correlation between the climatic and topographic factors with CL incidence. We found the CL distribution significantly clustered (Moran's Index=0.17, P<0.001) with the Ardestan and Aran va Bidgol (P<0.01) districts along with the Naein and Natanz districts (P<0.05) to be strong hotspot areas. Overlay analysis revealed a high incidence of CL in areas with relative humidity of 27-30%, mean temperature of 15-19°C, mean precipitation of 5-20 mm, maximum wind speed about 12-16 m/s and an altitude of 600-1,800 m. Our study showed that spatial analysis is a feasible approach for identifying spatial disease pattern and detecting hotspots of this infectious disease.

Finding the candidate sequence variants for diagnosis of hypertrophic cardiomyopathy in East Slovak patients.

Hypertrophic cardiomyopathy is a heterogeneous myocardial disease. Mutations appearing in several genes might be a potential cause of the disease. The aim of the study was to analyze selected exons of the sarcomeric and non-sarcomeric genes, with the purpose to identify potential candidate genetic variants and to understand etiopathogenetic mechanisms of hypertrophic cardiomyopathy in East Slovak patients. This study recruited 23 unrelated patients with hypertrophic cardiomyopathy, namely, 13 men and 10 women (mean age of 58.09±15.82years) and 25 healthy controls in order to determine the candidate sequence variants, in the selected exons of six cardiomyopathy genes (MYBPC3, MYH7, NEBL, SCN5A, TNNI3, TNNT2), by conventional capillary-based Sanger sequencing method and standard protocols. Molecular genetic results confirmed the presence of 43 sequence variants in the selected exons of six cardiomyopathy genes, 58.14% of detected variants were novel. The majority of detected sequence variants were confirmed within exon 23 of MYH7 gene. Only 11 genetic alterations were predicted to be potentially pathogenic. In our study, we identified known and novel sequence variants in 23 unrelated patients with hypertrophic cardiomyopathy, but we did not observe any strong mutation hotspot. The results of our study assumed that exon 23 of MYH7 gene can be in potential affinity to hypertrophic cardiomyopathy in our cohort of patients. The sequence variants identified in this study may be further investigated in order to determine their functions in disease pathogenesis and improve management, diagnosis, and treatment in Slovak patients.

Colorimetric and SERS dual-readout for assaying alkaline phosphatase activity by ascorbic acid induced aggregation of Ag coated Au nanoparticles

As an essential enzyme, alkaline phosphatase (ALP) has attracted considerable attention for its regulating effect to the dephosphorylation process in living organisms. Here, we present a colorimetric and surface enhanced Raman scattering (SERS) dual-readout approach for assaying ALP activity. The major advantage of dual-readout assay is the perfect combination of the merit of colorimetric and SERS, which not only allow rapid preliminary discrimination of ALP activity by the naked eye but also greatly improved the detection sensitivity by SERS. Specifically, 4-mercaptophenylboronic acid modified Ag coated gold nanoparticles (4-MPBA-Au@Ag NPs) are employed as the colorimetric and SERS bifunctional reporting nanoprobes. Upon the presence of ALP, the phosphate group in the ascorbic acid 2-phosphate (AAP) is cleaved to produce ascorbic acid (AA), which acted as boronic acid moieties receptors to control the aggregation of 4-MPBA-Au@Ag NPs. The color of 4-MPBA-Au@Ag NPs solutions had changed from bright orange to light brown to dark gray, simultaneously accompanied by a substantial enhancement of SERS-readouts for the strong Raman hot-spots between the aggregation of 4-MPBA-Au@Ag NPs. A distinguishable change in the color was observed at an ALP activity of 5.0U/L, meanwhile, SERS-readout sensing method showed a good linear relationship from 0.50 to 10.0U/L (R=0.997) with an exciting detection limit of 0.10U/L (signal-to-noise ratio of 3). In addition, the dual-readout approach developed here was applied for ALP inhibitor evaluation. With the simple, rapid/direct readout yet outstanding sensitivity, we anticipate that this method would greatly promote practical application in ALP-related early-stage diseases diagnosis.

Hot spot-mediated non-dissipative and ultrafast plasmon passage.

Plasmonic nanoparticles hold great promise as photon handling elements and as channels for coherent transfer of energy and information in future all-optical computing devices.1–5 Coherent energy oscillations between two spatially separated plasmonic entities via a virtual middle state exemplify electron-based population transfer, but their realization requires precise nanoscale positioning of heterogeneous particles.6–10 Here, we show the assembly and optical analysis of a triple particle system consisting of two gold nanoparticles with an inter-spaced silver island. We observe strong plasmonic coupling between the spatially separated gold particles mediated by the connecting silver particle with almost no dissipation of energy. As the excitation energy of the silver island exceeds that of the gold particles, only quasi-occupation of the silver transfer channel is possible. We describe this effect both with exact classical electrodynamic modeling and qualitative quantum-mechanical calculations. We identify the formation of strong hot spots between all particles as the main mechanism for the loss-less coupling and thus coherent ultra-fast energy transfer between the remote partners. Our findings could prove useful for quantum gate operations, but also for classical charge and information transfer processes.

Anticrossing double Fano resonances generated in metallic/dielectric hybrid nanostructures using nonradiative anapole modes for enhanced nonlinear optical effects

Third-harmonic generation with metallic or dielectric nanoparticles often suffer from, respectively, small modal volumes and weak near-field enhancements. This study propose and demonstrate that a metallic/dielectric hybrid nanostructure composed of a silver double rectangular nanoring and a silicon square nanoplate can be used to overcome these obstacles for enhanced third-harmonic generation. It is shown that the nonradiative anapole mode of the Si plate can be used as a localized source to excite the dark subradiant octupole mode of the Ag ring, and the mode hybridization leads to the formation of an antibonding and a bonding subradiant collective mode, thereby forming anticrossing double Fano resonances. With the strong coupling between individual particles and the effectively suppressed radiative losses of the Fano resonances, several strong hot spots are generated around the Ag ring due to the excitation of the octupole mode, and electromagnetic fields within the Si plate are also strongly amplified, making it possible to confine more incident energy inside the dielectric nanoparticle. Calculation results reveal that the confined energy inside the Si plate and the Ag ring for the hybrid structures can be about, respectively, more than three times and four orders stronger than that of the corresponding isolated nanoparticles, which makes the designed hybrid nanostructure a promising platform for enhanced third-harmonic generation.

Silver Nanoparticle-Decorated Shape-Memory Polystyrene Sheets as Highly Sensitive Surface-Enhanced Raman Scattering Substrates with a Thermally Inducible Hot Spot Effect.

In this study, an active surface-enhanced Raman scattering (SERS) substrate with a thermally inducible hot spot effect for sensitive measurement of Raman-active molecules was successfully fabricated from silver nanoparticle (AgNP)-decorated shape-memory polystyrene (SMP) sheets. To prepare the SERS substrate, SMP sheets were first pretreated with n-octylamine for effective decoration with AgNPs. By varying the formulation and condition of the reduction reaction, AgNP-decorated SMP (Ag@SMP) substrates were successfully prepared with optimized particle gaps to produce inducible hot spot effects on thermal shrink. High-quality SERS spectra were easily obtained with enhancement factors higher than 108 by probing with aromatic thiols. Several Ag@SMP substrates produced under different reaction conditions were explored for the creation of inducible hot spot effects. The results indicated that AgNP spacing is crucial for strong hot spot effects. The suitability of Ag@SMP substrates for quantification was also evaluated according to the detection of adenine. Results confirmed that prepared Ag@SMP substrates were highly suitable for quantitative analysis because they yielded an estimated limit of detection as low as 120 pg/cm2, a linear range of up to 7 ng/cm2, and a regression coefficient (R2) of 0.9959. Ag@SMP substrates were highly reproducible; the average relative standard deviation for all measurements was less than 10%.

Genetic Adaptation and Neandertal Admixture Shaped the Immune System of Human Populations

SummaryHumans differ in the outcome that follows exposure to life-threatening pathogens, yet the extent of population differences in immune responses and their genetic and evolutionary determinants remain undefined. Here, we characterized, using RNA sequencing, the transcriptional response of primary monocytes from Africans and Europeans to bacterial and viral stimuli—ligands activating Toll-like receptor pathways (TLR1/2, TLR4, and TLR7/8) and influenza virus—and mapped expression quantitative trait loci (eQTLs). We identify numerous cis-eQTLs that contribute to the marked differences in immune responses detected within and between populations and a strong trans-eQTL hotspot at TLR1 that decreases expression of pro-inflammatory genes in Europeans only. We find that immune-responsive regulatory variants are enriched in population-specific signals of natural selection and show that admixture with Neandertals introduced regulatory variants into European genomes, affecting preferentially responses to viral challenges. Together, our study uncovers evolutionarily important determinants of differences in host immune responsiveness between human populations.