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Two-dimensional materials (2DMs) have been used widely in constructing photodetectors (PDs) because of their advantages in flexible integration and ultrabroad operation wavelength range. Specifically, 2DM PDs on silicon have attracted much attention because silicon microelectronics and silicon photonics have been developed successfully for many applications. 2DM PDs meet the imperious demand of silicon photonics on low-cost, high-performance, and broadband photodetection. In this work, a review is given for the recent progresses of Si/2DM PDs working in the wavelength band from near-infrared to mid-infrared, which are attractive for many applications. The operation mechanisms and the device configurations are summarized in the first part. The waveguide-integrated PDs and the surface-illuminated PDs are then reviewed in details, respectively. The discussion and outlook for 2DM PDs on silicon are finally given.

A novel software has been created to comprehensively characterize covalent modifications of DNA through mass spectral analysis of enzymatically hydrolyzed DNA using the neutral loss of 2'-deoxyribose, a nearly universal MS2 fragmentation process of protonated 2'-deoxyribonucleosides. These covalent modifications termed DNA adducts form through xenobiotic exposures or by reaction with endogenous electrophiles and can induce mutations during cell division and initiate carcinogenesis. DNA adducts are typically present at trace levels in the human genome, requiring a very sensitive and comprehensive data acquisition and analysis method. Our software, wSIM-City, was created to process mass spectral data acquired by a wide selected ion monitoring (wSIM) with gas-phase fractionation and coupled to wide MS2 fragmentation. This untargeted approach can detect DNA adducts at trace levels as low as 1.5 adducts per 109 nucleotides. This level of sensitivity is sufficient for comprehensive analysis and characterization of DNA modifications in human specimens.

Osteoporosis bone defect is a refractory orthopaedic disease which characterized by impaired bone quality and bone regeneration capacity. Current therapies, including antiosteoporosis drugs and artificial bone grafts, are not always satisfactory. Herein, a strontium-substituted calcium phosphate silicate bioactive ceramic (Sr-CPS) was fabricated. In the present study, the extracts of Sr-CPS were prepared for in vitro study and Sr-CPS scaffolds were used for in vivo study. The cytocompatibility, osteogenic and osteoclastogenic properties of Sr-CPS extracts were characterized in comparison to CPS. Molecular mechanisms were also evaluated by Western blot. Sr-CPS extracts were found to promote osteogenesis by upregulating Wnt/β-catenin signal pathways and inhibit osteoclastogenesis through downregulating NF-κB signal pathway. In vivo, micro-CT, histological and histomorphometric observation were conducted after 8 weeks of implantation to evaluate the bone formation using calvarial defects model in ovariectomized rats. Compared with CPS, Sr-CPS significantly promoted critical sized ovariectomy (OVX) calvarial defects healing. Among all the samples, Sr-10 showed the best performance due to a perfect match of bone formation and scaffold degradation rates. Overall, the present study demonstrated that Sr-CPS ceramic can dually modulate both bone formation and resorption, which might be a promising candidate for the reconstruction of osteoporotic bone defect., Graphical abstract Image 1, Highlights • Easy-to-perform and cost-effective fabrication of Sr-CPS scaffold. • Dual modulation of bone formation and resorption. • Outstanding performances in the osteoporotic bone defect healing process.

Tendon repair was an important part during tendon to bone healing. In the present study, heparin molecules were immobilized on the aminolyzed PCL surface to improve the cellular bioactivity for potential tendon repair. The effects of heparin immobilization on protein adsorption behavior and cellular bioactivity of NIH3T3 and ATDC5 cells were investigated. The results were shown as follows.

Long-term function of dental implants relies on not only stable osseointegration but also strong soft tissue-sealing ability. Ideal soft tissue sealing around implants is an effective protective barrier between the external environment and alveolar bone, preventing the invasion of bacteria that is considered as a vital trigger of irreversible marginal bone loss. Carbon-based materials have been reported to be beneficial to soft tissue sealing, which can be regulated through the hybridization type of carbon atoms (sp2 or sp3), but its internal mechanism is still not clear. In this work, graphene oxide with both sp2- and sp3-hybridized carbons was electrophoretic deposited on titanium and reduced to regulate the hybridization type of carbon atoms to investigate its effect and possible mechanism on human gingival fibroblasts (HGFs). X-ray photoelectron spectroscopy and Raman mapping test show the increase of sp2 domain content and the decrease of their size after reduction. Through computer simulation, the possible mechanism of the decrease of sp2 domain size was proposed. In vitro studies disclose that the HGFs exhibit higher proliferation rate, better adhesion, and migration ability with the increase of sp2 domains and the decrease of their sizes. It may be due to the amount and size of sp2 domains that synergistically regulate the amount and properties of adsorbed proteins, thereby influencing the cellular behaviors of HGFs. Our results may offer a different perspective on material designing and academic research to enhance the soft tissue integration of implants.

Frequent exposure to chemicals in the environment, diet, and endogenous electrophiles leads to chemical modification of DNA and the formation of DNA adducts. Some DNA adducts can induce mutations during cell division and, when occurring in critical regions of the genome, can lead to the onset of disease, including cancer. The targeted analysis of DNA adducts over the past 30 years has revealed that the human genome contains many types of DNA damages. However, a long-standing limitation in conducting DNA adduct measurements has been the inability to screen for the total complement of DNA adducts derived from a wide range of chemicals in a single assay. With the advancement of high-resolution mass spectrometry (MS) instrumentation and new scanning technologies, nontargeted “omics” approaches employing data-dependent acquisition and data-independent acquisition methods have been established to simultaneously screen for multiple DNA adducts, a technique known as DNA adductomics. However, notable challenges in data processing must be overcome for DNA adductomics to become a mature technology. DNA adducts occur at low abundance in humans, and current softwares do not reliably detect them when using common MS data acquisition methods. In this perspective, we discuss contemporary computational tools developed for feature finding of MS data widely utilized in the disciplines of proteomics and metabolomics and highlight their limitations for conducting nontargeted DNA-adduct biomarker discovery. Improvements to existing MS data processing software and new algorithms for adduct detection are needed to develop DNA adductomics into a powerful tool for the nontargeted identification of potential cancer-causing agents.

Multimode silicon photonics have drawn tremendous attention because the introduction of higher-order modes greatly enhances the capacity of mode-division-multiplexing (MDM) data transmission systems as well as improves the flexibility of on-chip photonic device designs. As the cornerstone of multimode silicon photonics, plentiful multimodemanipulation photonic devices have been developed successfully. On the other hand, more and more emerging applications have been stimulated by higher-order modes introduced in multimode silicon photonics. This paper gives a review for our recent processes in the development of multimode silicon photonic devices. Keywords: mode, multiplexer, conversion, bend, filter, silicon, waveguide.

Epidemiological studies have linked aromatic amines (AAs) from tobacco smoke and some occupational exposures with bladder cancer risk. Several epidemiological studies have also reported a plausible role for structurally related heterocyclic aromatic amines present in tobacco smoke or formed in cooked meats with bladder cancer risk. DNA adduct formation is an initial biochemical event in bladder carcinogenesis. We examined paired fresh-frozen (FR) and formalin-fixed paraffin-embedded (FFPE) non-tumor bladder tissues from 41 bladder cancer patients for DNA adducts of 4-aminobiphenyl (4-ABP), a bladder carcinogen present in tobacco smoke, and 2-amino-9H-pyrido[2,3-b]indole, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine, and 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline, possible human carcinogens, which occur in tobacco smoke and cooked meats. These chemicals are present in urine of tobacco smokers or omnivores. Targeted DNA adduct measurements were done by ultra-performance liquid chromatography-electrospray ionization multi-stage hybrid Orbitrap MS. N-(2′-Deoxyguanosin-8-yl)-4-ABP (N-(dG-C8)-4-ABP) was the sole adduct detected in FR and FFPE bladder tissues. Twelve subjects (29%) had N-(dG-C8)-4-ABP levels above the limit of quantification, ranging from 1.4 to 33.8 adducts per 10(9) nucleotides (nt). DNA adducts of other human AA bladder carcinogens, including 2-naphthylamine (2-NA), 2-methylaniline (2-MA), 2,6-dimethylaniline (2,6-DMA), and lipid peroxidation (LPO) adducts were screened for in bladder tissue, by our untargeted data-independent adductomics method, termed wide-selected ion monitoring (wide-SIM)/MS(2). Wide-SIM/MS(2) successfully detected N-(dG-C8)-4-ABP, N-(2′-deoxyadenosine-8-yl)-4-ABP and the presumed hydrazo linked adduct, N-(2′-deoxyguanosin-N(2)-yl)-4-ABP, and several LPO adducts in bladder DNA. Wide-SIM/MS(2) detected multiple DNA adducts of 2-NA, 2-MA and, 2,6-DMA, when calf thymus DNA was modified with reactive intermediates of these carcinogens. However, these AA-adducts were below the limit of detection in unspiked human bladder DNA (< 1 adduct per 10(8) nt). Wide-SIM/MS(2) can screen for many types of DNA adducts formed with exogenous and endogenous electrophiles and will be employed to identify DNA adducts of other chemicals that may contribute to the etiology of bladder cancer.

Due to the dissimilar features between the tendon and bone, tendon to bone healing is the most challenging problems in sports medicine. In the present work, a novel bioactive calcium phosphate silicate ceramic (CPS) was coated on the surface of PLGA films using electron beam evaporation (EBE) technique to prepare a tailorable composite film with layered chemical composition similar to tendon-bone interface. The physicochemical behaviors of the CPS-PLGA composite films were characterized and the cytocompatibility were also investigated. It was found that the CPS-modified samples exhibited a significantly improved hydrophilicity and a more negative zeta potential. Cell culture results showed that the CPS-modified samples were beneficial to the attachment and proliferation of rBMSCs and NIH3T3 cells. CPS-modified samples also showed an improved osteogenic activity. The results suggested that CPS-modified PLGA films have great potentials for tendon-bone healing.

Currently, graphene and its derivatives, used for surface modification of orthopedic and dental implants, are mainly in the form of two-dimensional planar structure. There is little information of three dimensional porous graphene nanosheets used as coating materials of titanium and its alloys. In the present study, three dimensional porous graphene nanosheets were first synthesized on the pure titanium surface. The physicochemical properties and osteogenic activity of the three dimensional porous graphene nanosheets-modified titanium (rGO@Ti) were systematically investigated. The results suggested that rGO@Ti showed super hydrophilicity, rough surface and excellent biocompatibility, and could enhance alkaline phosphatase (ALP) activity, extracellular matrix (ECM) mineralization and collagen secretion of rat bone mesenchymal stem cells (rBMSCs). Meanwhile, the expressions of osteogenesis related genes containing ALP, bone morphogenic protein-2 (BMP-2), osteocalcin (OCN), and osteopontin (OPN) on rGO@Ti were improved. The osteogenic differentiation of rBMSCs on rGO@Ti may be ascribed to both its superior protein adsorption ability and physical stimulation induced by the unique structure of three dimensional porous graphene nanosheets.

Mass spectrometry-based DNA adductomics is an emerging approach for the human biomonitoring of hazardous chemicals. A mass spectral database of DNA adducts will be created for the scientific community to investigate the associations between chemical exposures, DNA damage, and disease risk.

A graphene photodetector based on ultra-thin silicon waveguide at 1.55μm is proposed. By reducing the silicon core thickness, the fundamental TE waveguide mode is less confined and light-graphene interaction is enhanced. Benefiting from the ultrathin silicon waveguide and reflector structure, the graphene absorption coefficient reaches 0.36 dB/μm. A 10nm-thick CVD-grown hexagonal boron nitride is covered on the graphene to improve the device performance. With the help of metal-graphene-metal structure, the contact resistance is reduced dramatically. The devices have shown a responsivity of 1.4 mA/W at 0 V bias and 23.1 mA/W at 0.3 V bias with 0.24 mW input optical power. The measured 3-dB bandwidth is 17GHz under 0V bias voltage at 1550 nm.

Silicon photonics has attracted much attention because of the CMOS compatibility, high integrated density, etc. However, silicon is not a good option for active photonic integrated devices due to its indirect-bandgap structure. Recently, two-dimensional (2D) materials, such as graphene and black phosphorus (BP), exhibit excellent optical and electronic properties, and thus provide a potential option for realizing active photonic integrated devices on silicon. In this paper, we present our recent works on silicon/2D-materials photonic integrated devices for photodetection and thermal-tuning.

Reactive oxygen species (ROS) and chronic inflammation contribute to DNA damage of many organs, including the prostate. ROS cause oxidative damage to biomolecules, such as lipids, proteins, and nucleic acids, resulting in the formation of toxic and mutagenic intermediates. Lipid peroxidation (LPO) products covalently adduct to DNA and can lead to mutations. The levels of LPO DNA adducts reported in humans range widely. However, a large proportion of the DNA adducts may be attributed to artifact formation during the steps of isolation and nuclease digestion of DNA. We established a method that mitigates artifacts for most LPO adducts during the processing of DNA. We have applied this methodology to measure LPO DNA adducts in the genome of prostate cancer patients, employing ultra-high-performance liquid chromatography electrospray ionization ion trap multistage mass spectrometry. Our preliminary data show that DNA adducts of acrolein, 6-hydroxy-1,N(2)-propano-2′-deoxyguanosine (6-OH-PdG) and 8-hydroxy-1,N(2)-propano-2′-deoxyguanosine (8-OH-PdG) (4 – 20 adducts per 10(7) nucleotides) are more prominent than etheno (ε) adducts (< 0.5 adducts per 10(8) nucleotides). This analytical methodology will be used to examine the correlation between oxidative stress, inflammation, and LPO adduct levels in patients with benign prostatic hyperplasia and prostate cancer.

This Letter studies the effect of the nitrogen capture ability of quantum dots on resistive switching characteristics of AlN-based resistive random access memory. We prepared a single layer AlN device and four types of AlN/PbS quantum dot stacked structure devices with different concentrations. Compared with the single layer AlN device, the AlN/PbS quantum dot stacked structure devices exhibit excellent resistive switching characteristics, such as forming-free, low power consumption, and excellent stability. We propose that the resistive switching process is determined by the migration of nitrogen ions and the lead sulfide (PbS) quantum dot layer as a natural nitrogen ion reservoir, which can improve the resistive switching characteristics. Moreover, the size of the natural nitrogen ion reservoir can be modulated by changing the concentration of quantum dots.

The tendon enthesis is a very complex tissue interface that connects a flexible tissue (tendon) to a stiff tissue (bone). Few available forms of gradient scaffolds with multiple components have been fabricated for applications in vivo because of the complexities of enthesis. In the present work, gradient-poly(e-caprolactone)/calcium phosphate silicate (G-P/C) composite films were fabricated with tape casting technique. Films with different P/C ratio were used to evaluate the material’s properties and effects of composition on cellular behaviors. The results showed that the G-P/C composite film offered a gradually changing composition transition. The higher levels of calcium phosphate silicate of each film stimulated stronger osteogenic differentiation and mineralized matrix deposition. When the films were interposed between the supraspinatus tendon and humerus bone, the G-P/C composite film group exhibited more tissue cellularity, better collagen alignment, better gradient mineralized cartilage formation and gradient Ca distribution than other groups. All these histological improvements were well consistent with the biomechanical results of the G-P/C composite film group. Thus, the G-P/C composite film may be a promising scaffold for tendon-to-bone interface engineering.

A major impediment in the biomonitoring of DNA adducts is the lack of fresh-frozen biopsy samples available for biomarker research. However, archived formalin-fixed, paraffin-embedded (FFPE) tissues with a clinical diagnosis of disease are often accessible. We have established a method to fully unravel DNA crosslinks in FFPE specimens under mild conditions that preserve the structural integrity of DNA adducts. Our targeted, quantitative mass spectrometry measurements employing ion trap or high-resolution Orbitrap mass spectrometry require less than ten micrograms of DNA with limits of quantification at three adducts per 109 nucleotides. We have successfully screened FFPE tissues of rodents exposed to tobacco and dietary carcinogens and reported adduct levels comparable to those of matching fresh-frozen tissues. Our technology has been employed to identify a DNA adduct of aristolochic acid, a potent urothelial carcinogen present in Chinese herbal medicines, in human FFPE kidney blocks stored at ambient temperature for up to nine years. The method also detected DNA adducts of the bladder carcinogen 4-aminobiphenyl in human FFPE bladder, and a DNA adduct of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine, a heterocyclic aromatic amine formed in cooked meats and a potential prostate carcinogen, in FFPE prostate specimens of prostate cancer patients. Thus, the technology is versatile and can be employed to screen for DNA adducts formed with a wide range of environmental and dietary carcinogens. The ability to retrospectively analyze FFPE tissues for DNA adducts for which there is a clinical diagnosis of disease opens a previously untapped source of biospecimens for molecular epidemiology studies seeking the causal role of environmental chemicals in cancer etiology. With the recent improvements in the sensitivity and scanning rates of high-resolution MS instruments, such as quadrupole time-of-flight and Orbitrap MS detectors, it is now possible to screen for a wide array of DNA damage in the human genome using DNA adductomics approaches. We have adapted data-dependent and data-independent scanning techniques originated from proteomics and metabolomics to screen for DNA adducts of the genome. DNA adductomics is a new and developing technology for human exposure assessment. As the analytic technology matures and bioinformatics tools become available for analysis of the mass spectral data, DNA adductomics can advance our understanding of the role chemical exposures play in DNA damage and disease risk. Citation Format: Byeong Hwa Yun, Jingshu Guo, Scott Walmsley, Paari Murugan, Christopher J. Weight, Peter W. Villalta, Robert J. Turesky. Untapped biospecimens and novel mass spectrometry scanning techniques for DNA adductomics [abstract]. In: Proceedings of the AACR Special Conference on Environmental Carcinogenesis: Potential Pathway to Cancer Prevention; 2019 Jun 22-24; Charlotte, NC. Philadelphia (PA): AACR; Can Prev Res 2020;13(7 Suppl): Abstract nr A33.

Objectives To fabricate polymer-infiltrated silicon nitride composite (PISNC) and evaluate the potential of PISNC in dental application. Methods Porous silicon nitride (Si3N4) ceramics were fabricated through gelcasting and pressureless sintering. Polymer infiltrating was carried out then and composites were obtained after curing of polymer. Flexural strength and microstructures of porous ceramic scaffolds and polymer-infiltrated composites were obtained by three-point bending and SEM, respectively. Phase distributions of polymer-infiltrated ceramics were observed by EDS. Human gingival fibroblast cells (HGFs) were used to evaluate the cytocompatibility and IL-6 release. The cell morphology were observed by SEM. The amount of released IL-6 was investigated using ELISA test system. Results Porosity and mechanical strength of porous ceramics ranged from 45.1 to 49.3% and 171.8–262.3 MPa, respectively. The bicontinuous structure of polymer-infiltrated composites possessed them with excellent mechanical properties. Porosity and mechanical strength of polymer-infiltrated Si3N4 composites ranged from 1.94 to 2.28% and 273–385.3 MPa, respectively. Additionally, the PISNC enhanced the initial adhesion and spreading activity of HGFs compared with PMMA. The PISNC showed similar IL-6 release performance with PMMA samples. Significances The PISNC is a promising candidate for dental restorations and high-load medical applications.

The measurement of DNA adducts provides important information about human exposure to genotoxic chemicals and can be employed to elucidate mechanisms of DNA damage and repair. DNA adducts can serve as biomarkers for interspecies comparisons of the biologically effective dose of procarcinogens and permit extrapolation of genotoxicity data from animal studies for human risk assessment. One major challenge in DNA adduct biomarker research is the paucity of fresh frozen biopsy samples available for study. However, archived formalin-fixed paraffin-embedded (FFPE) tissues with clinical diagnosis of disease are often available. We have established robust methods to recover DNA free of crosslinks from FFPE tissues under mild conditions which permit quantitative measurements of DNA adducts by liquid chromatography-mass spectrometry. The technology is versatile and can be employed to screen for DNA adducts formed with a wide range of environmental and dietary carcinogens, some of which were retrieved from section-cuts of FFPE blocks stored at ambient temperature for up to nine years. The ability to retrospectively analyze FFPE tissues for DNA adducts for which there is clinical diagnosis of disease opens a previously untapped source of biospecimens for molecular epidemiology studies that seek to assess the causal role of environmental chemicals in cancer etiology.

Considerable evidence suggests that environmental factors, including diet and cigarette smoke, are involved in the pathogenesis of colon cancer. Carcinogenic nitroso compounds (NOC), such as N-nitrosodimethylamine (NDMA), are present in tobacco and processed red meat, and NOC have been implicated in colon cancer. Azoxymethane (AOM), commonly used for experimental colon carcinogenesis, is an isomer of NDMA, and it produces the same DNA adducts as does NDMA. Heterocyclic aromatic amines (HAAs) formed during the combustion of tobacco and high-temperature cooking of meats are also associated with an elevated risk of colon cancer. The most abundant carcinogenic HAA formed in tobacco smoke is 2-amino-9H-pyrido[2,3-b]indole (AαC), whereas 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ) is the most potent carcinogenic HAA formed during the cooking of meat and fish. However, the comparative tumor-initiating potential of AαC, MeIQ, and AOM is unknown. In this report, we evaluate the formation of DNA adducts as a measure of genotoxicity, and the induction of colonic aberrant crypt foci (ACF) and dysplastic ACF, as an early measure of carcinogenic potency of these compounds in the colon of male A/J mice. Both AαC and AOM induced a greater number of DNA adducts than MeIQ in the liver and colon. AOM induced a greater number of ACF and dysplastic ACF than either AαC or MeIQ. Conversely, based on adduct levels, MeIQ-DNA adducts were more potent than AαC- and AOM-DNA adducts at inducing ACF. Long-term feeding studies are required to relate levels of DNA adducts, induction of ACF, and colon cancer by these colon genotoxicants.

In this paper, we present a new 3-D structure for the InP-based avalanche photodiode, aiming at decreasing the excess noise factor. To the best of our knowledge, it is the first time new device designs based on the recently developed 3-D spatial dead space model in 2014 have been proposed. In addition, we also propose a methodology, i.e., the 2-D planar absorption distribution projection technique, for further optimizing the 3-D model. According to our theoretical simulation results, by combining photonic crystal and selective area doping, the effective k values of InP and In0.52Al0.48As can be reduced to as low as ~0.19 and as ~0.13, respectively. Meanwhile, the optimal thickness of the multiplication region is larger than 0.45 μm, which reduces the tunneling effect. The detailed parameter optimization process, including optics, electronics, and material, is comprehensively presented. The examples in this paper also provide a fresh idea for researchers to foretell and design new photodetectors with the 3-D structure.

2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is a carcinogenic heterocyclic aromatic amine formed in cooked meat. The use of naturally colored hair containing PhIP can serve as a long-term biomarker of exposure to this carcinogen. However, the measurement of PhIP in dyed hair, a cosmetic treatment commonly used by the adult population, is challenging because the dye process introduces into the hair matrix a complex mixture of chemicals that interferes with the measurement of PhIP. The high-resolution scanning features of the Orbitrap Fusion mass spectrometer were employed to biomonitor PhIP in dyed hair. Because of the complexity of chemicals in the hair dye, the consecutive reaction monitoring of PhIP at the MS(3) scan stage was employed to selectively remove the isobaric interferences. The limit of quantification (LOQ) of PhIP was 84 parts-per-trillion (ppt) employing 50 mg of hair. Calibration curves were generated in dyed hair matrixes and showed good linearity (40-1000 pg PhIP/g hair) with a goodness-of-fit regression value of r(2) > 0.9978. The within-day (between-day) coefficients of variation were 7.7% (17%) and 5.4% (6.1%), respectively, with dyed hair samples spiked with PhIP at 200 and 600 ppt. The levels of PhIP accrued in dyed hair from volunteers on a semicontrolled feeding study who ingested known levels of PhIP were comparable to the levels of PhIP accrued in hair of subjects with natural hair color. The method was successfully employed to measure PhIP in nondyed and dyed hair biospecimens of participants in a case-control study of colorectal adenoma on their regular diet.

Hazardous chemicals in the environment and diet or their electrophilic metabolites can form adducts with genomic DNA, which can lead to mutations and the initiation of cancer. In addition, reactive intermediates can be generated in the body through oxidative stress and damage the genome. The identification and measurement of DNA adducts are required for understanding exposure and the causal role of a genotoxic chemical in cancer risk. Over the past three decades, (32)P-postlabeling, immunoassays, gas chromatography/mass spectrometry, and liquid chromatography/mass spectrometry (LC/MS) methods have been established to assess exposures to chemicals through measurements of DNA adducts. It is now possible to measure some DNA adducts in human biopsy samples, by LC/MS, with as little as several milligrams of tissue. In this review article, we highlight the formation and biological effects of DNA adducts, and highlight our advances in human biomonitoring by mass spectrometric analysis of formalin-fixed paraffin-embedded tissues, untapped biospecimens for carcinogen DNA adduct biomarker research.

Background Organo-montmorillonite (OMt) is widely used in oil well drilling fluids, paint, grease, cosmetics, and personal care products. Nanocomposites which are prepared using organoclays and polymers. Generally, organo-montmorillonite can be prepared using ion-exchange reactions with cationic surfactants. However, cationic-organo-montmorillonite (COMt) has poorer thermal stability. In addition, the preparation process of traditional OMt uses a large amount of water. The process would emit a large amount of effluent and increase cost. Objective The aim of this work is to prepare nonionic-organo-montmorillonite (NOMt) and anionic-nonionic-organo-montmorillonite (ANOMt) using ball milling method. And NOMt and ANOMt are of better thermal stability than COMt. Method Organo-montmorillonite was prepared using ball milling method and characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), Fourier transform infrared (FT-IR), Thermogravimetric (TG) analysis, differential thermal analysis (DTA) and contact angle test. Results XRD analysis indicated that the interlayer spacing of Ca 2+ -montmorillonite (Ca-Mt) was expanded. ANOMt showed a large d-spacing above 5.0 nm. SEM analysis demonstrated that the ANOMt was flaky in substance. FT-IR spectra proved that the chemical environment of the surfactants changed. TG and DTA results showed that the thermal stabilities of NOMt and ANOMt were better than that of COMt. FT-IR and thermal analysis indicated that the interlayer water was replaced. The contact angle tests of the samples indicated that NOMt and ANOMt were of oleophilic property. Conclusion Ca-Mt was modified with nonionic surfactant and anionic surfactant by ball milling method, without any added water. NOMt and ANOMt were prepared. The thermal stabilities of NOMt and ANOMt are better than COMt. Dual mechanisms of intercalation and stacking were proposed.

Long-term exposures to environmental toxicants and endogenous electrophiles are causative factors for human diseases including cancer. DNA adducts reflect the internal exposure to genotoxicants and can serve as biomarkers for risk assessment. Liquid chromatography-multistage mass spectrometry (LC-MSn) is the most common method for biomonitoring DNA adducts, generally targeting single exposures and measuring up to several adducts. However, the data often provide limited evidence for a role of a chemical in the etiology of cancer. An “untargeted” method is required that captures global exposures to chemicals, by simultaneously detecting their DNA adducts in the genome; some of which may induce cancer-causing mutations. We established a wide selected ion monitoring tandem mass spectrometry (Wide-SIM/MS2) screening method utilizing ultra-performance-LC nanoelectrospray ionization Orbitrap MSn with on-line trapping to enrich bulky, non-polar adducts. Wide-SIM scan events are followed by MS2 scans to screen for modified nucleosides by co-eluting peaks containing precursor and fragment ions differing by -116.0473 Da, attributed to the neutral loss of deoxyribose. Wide-SIM/MS2 was shown to be superior in sensitivity, specificity, and breadth of adduct coverage to other tested adductomic methods with detection possible at adduct levels as low as 4 per 109 nucleotides. Wide-SIM/MS2 data can be analyzed in a “targeted” fashion by generation of extracted ion chromatograms or in an “untargeted” fashion where a chromatographic peak-picking algorithm can be used to detect putative DNA adducts. Wide-SIM/MS2 successfully detected DNA adducts, derived from chemicals in the diet and traditional medicines and from lipid peroxidation products, in human prostate and renal specimens.

We investigate the light absorption enhancement in waveguide Schottky photodetector integrated with ultrathin metal/silicide stripe, which can provide high internal quantum efficiency. By using aab0-quasi-TE hybrid modes for the first time, a high absorptance of 95.6% is achieved in 5 nm thick Au stripe with area of only 0.14 μmsup2/sup, without using resonance structure. In theory, the responsivity, dark current, and 3dB bandwidth of the corresponding device are 0.146 A/W, 8.03 nA, and 88 GHz, respectively. For most silicides, the quasi-TM mode should be used in this device, and an optimized PtSi device has a responsivity of 0.71 A/W and a dark current of 35.9 μA.

Graphene has emerged as a promising solution for on-chip ultrafast photodetection for its advantages of easy integration, high mobility, adjustable chemical potential, and wide operation wavelength range. In order to realize high-performance photodetectors, it is very important to achieve efficient light absorption in the active region. In this work, a compact and high-speed hybrid silicon/graphene photodetector is proposed and demonstrated by utilizing an ultra-thin silicon photonic waveguide integrated with a loop mirror. With this design, the graphene absorption rate for the fundamental mode of TE polarization is improved by ∼5 times compared to that in the conventional hybrid silicon/graphene waveguide with hco=220 nm. One can achieve 80% light absorption ratio within the active-region length of only 20 µm for the present silicon/graphene waveguide photodetector at 1550 nm. For the fabricated device, the responsivity is about 25 mA/W under 0.3V bias voltage and the 3-dB bandwidth is about 17 GHz. It is expected to achieve very high bandwidth by introducing high-quality Al2O3 insulator layers and reducing the graphene channel length in the future.

The measurement of DNA adducts, the covalent modifications of DNA upon the exposure to the environmental and dietary genotoxicants and endogenously produced electrophiles, provides molecular evidence for DNA damage. With the recent improvements in the sensitivity and scanning speed of mass spectrometry (MS) instrumentation, particularly high-resolution MS, it is now feasible to screen for the totality of DNA damage in the human genome through DNA adductomics approaches. Several MS platforms have been used in DNA adductomic analysis, each of which has its strengths and limitations. The loss of 2′-deoxyribose from the modified nucleoside upon collision-induced dissociation is the main transition feature utilized in the screening of DNA adducts. Several advanced data-dependent and data-independent scanning techniques originated from proteomics and metabolomics have been tailored for DNA adductomics. The field of DNA adductomics is an emerging technology in human exposure assessment. As the analytical technology matures and bioinformatics tools become available for analysis of the MS data, DNA adductomics can advance our understanding about the role of chemical exposures in DNA damage and disease risk.

Epidemiologic studies have reported an association between frequent consumption of well-done cooked meats and prostate cancer risk. However, unambiguous physiochemical markers of DNA damage from carcinogens derived from cooked meats, such as DNA adducts, have not been identified in human samples to support this paradigm. We have developed a highly sensitive nano-LC-Orbitrap MSn method to measure DNA adducts of several carcinogens originating from well-done cooked meats, tobacco smoke and environmental pollution including: 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), 2-amino-9H-pyrido[2,3-b]indole (AαC), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), benzo[a]pyrene (B[a]P) and 4-aminobiphenyl (4-ABP). The limit of quantification (LOQ) of the major deoxyguanosine (dG) adducts of these carcinogens ranged between 1.3 – 2.2 adducts per 109 nucleotides per 2.5 μg DNA assayed. The DNA adduct of PhIP, N-(deoxyguanosin-8-yl)-PhIP (dG-C8-PhIP) was identified in 11 out of 35 patients, at levels ranging from 2 to 120 adducts per 109 nucleotides. The dG-C8 adducts of AαC, MeIQx, and the B[a]P adduct, 10-(deoxyguanosin-N2-yl)-7,8,9-trihydroxy-7,8,9,10-tetrahydrobenzo[a]pyrene (dG-N2-B[a]PDE) were not detected in any specimen, whereas N-(deoxyguanosin-8-yl)-4-ABP (dG-C8-4-ABP) was identified in one subject (30 adducts per 109 nucleotides). PhIP DNA adducts also were recovered quantitatively from formalin fixed paraffin embedded (FFPE) tissues, signifying FFPE tissues can serve as biospecimens for carcinogen DNA adduct biomarker research. Our biomarker data provide support to the epidemiological observations implicating PhIP, one of the most mass-abundant heterocyclic aromatic amines formed in well-done cooked meats, as a DNA damaging agent that may contribute to the etiology of prostate cancer.

Humans are continuously exposed to hazardous chemicals in the environment. These chemicals or their electrophilic metabolites can form adducts with genomic DNA, which can lead to mutations and the initiation of cancer. The identification of DNA adducts is required for understanding exposure and the etiological role of a genotoxic chemical in cancer risk. The analytical chemist is confronted with a great challenge because the levels of DNA adducts generally occur at

DNA adducts are a measure of internal exposure to genotoxicants and an important biomarker for human risk assessment. However, the employment of DNA adducts as biomarkers in human studies is often restricted because fresh-frozen tissues are not available. In contrast, formalin-fixed paraffin-embedded (FFPE) tissues with clinical diagnosis are readily accessible. Recently, our laboratory reported that DNA adducts of aristolochic acid, a carcinogenic component of Aristolochia herbs used in traditional Chinese medicines worldwide, can be recovered quantitatively from FFPE tissues. In this study, we have evaluated the efficacy of our method for retrieval of DNA adducts from archived tissue by measuring DNA adducts derived from four other classes of human carcinogens: polycyclic aromatic hydrocarbons (PAHs), aromatic amines, heterocyclic aromatic amines (HAAs), and N-nitroso compounds (NOCs). Deoxyguanosine (dG) adducts of the PAH benzo[a]pyrene (B[a]P), 10-(deoxyguanosin-N(2)-yl)-7,8,9-trihydroxy-7,8,9,10-tetrahydrobenzo[a]pyrene (dG-N(2)-B[a]PDE); the aromatic amine 4-aminobiphenyl (4-ABP), N-(deoxyguanosin-8-yl)-4-aminobiphenyl (dG-C8-4-ABP); the HAA 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), N-(deoxyguanosin-8-yl)-PhIP (dG-C8-PhIP); and the dG adducts of the NOC 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), O(6)-methyl-dG (O(6)-Me-dG) and O(6)-pyridyloxobutyl-dG (O(6)-POB-dG), formed in liver, lung, bladder, pancreas, or colon were recovered in comparable yields from fresh-frozen and FFPE preserved tissues of rodents treated with the procarcinogens. Quantification was achieved by ultraperformance liquid chromatography coupled with electrospray ionization ion-trap multistage mass spectrometry (UPLC/ESI-IT-MS(3)). These advancements in the technology of DNA adduct retrieval from FFPE tissue clear the way for use of archived pathology samples in molecular epidemiology studies designed to assess the causal role of exposure to hazardous chemicals with cancer risk.

Mass spectrometry has played a key role in identifying the members of a series of gold clusters, which has enabled the development of magic-number cluster theory. The successes of the gold cluster system have yet to be repeated in another metal cluster system, however. Silver clusters in particular have proven to be challenging due to their relative instability compared with gold clusters. Using the well-characterized gold nanocluster, Au(25)(SG)(18), we present optimized electrospray ionization mass spectrometry (ESI-MS) instrumental parameters for the maximal transmission of the intact cluster. Parameters shown to have the largest effect on intact cluster transmission/detection include trap and transfer collision energy, source temperature, and cone gas flow rate. Herein we describe a general strategy to acquire mass spectra of fragile metal clusters with reliable mass assignments. By also optimizing sample solution conditions, high-quality ESI mass spectra of a prototypical silver:glutathione (Ag:SG) cluster were obtained without significant fragmentation. By using gentle conditions and solution conditions designed to stabilize the clusters, fragmentation was dramatically reduced and mass spectra with isotopic resolution were measured. Using this strategy, we have made the first formula assignment for a ligand-protected Ag cluster of Ag(32)(SG)(19).

We present the first complete amino acid sequences of Snow leopard (Uncia uncia) and Amur tiger (Panthera tigris altaica) hemoglobin (Hb) determined using a combined ESI MS and X-ray crystallography approach. Using mass spectrometry alone, we were able to achieve 81%, 90%, 87% and 72% sequence coverage for the α-, and β-globins of Snow leopard Hb and the α-, and β-chain of Amur tiger Hb, respectively. The incomplete mass spectrometry-determined sequences were used to process X-ray diffraction data of Snow leopard and Amur tiger Hb crystals solved to 2.1 A and 1.8 A, respectively. Using tandem mass spectrometry in concert with the electron density maps from X-ray structures, we were able to not only achieve 100% coverage of all amino acid sequences, but to also distinguish between isomeric (leucine and isoleucine) and isobaric (glutamine and lysine) residues. These results demonstrate the synergy between mass spectrometry and X-ray crystallography for the determination of full amino acid sequence coverage of abundant proteins.

The field of silicon nanophotonics has attracted considerable attention in the past decade because of its unique advantages, including complementary metal–oxide–semiconductor (CMOS) compatibility and the ability to achieve an ultra-high integration density. In particular, silicon nanophotonic integrated devices for on-chip light manipulation have been developed successfully and have played very import roles in various applications. In this paper, we review the recent progress of silicon nanophotonic devices for on-chip light manipulation, including the static type and the dynamic type. Static on-chip light manipulation focuses on polarization/mode manipulation, as well as light nanofocusing, while dynamic on-chip light manipulation focuses on optical modulation/switching. The challenges and prospects of high-performance silicon nanophotonic integrated devices for on-chip light manipulation are discussed.

Improvements in neutron diffraction instrumentation are affording the opportunity to re-examine the structures of vertebrate hemoglobins and to interrogate proton and solvent position changes between the different quaternary states of the protein. For hemoglobins of unknown primary sequence, structural studies of cyanomethemoglobin (CNmetHb) are being used to help to resolve sequence ambiguity in the mass spectra. These studies have also provided additional structural evidence for the involvement of oxidized hemoglobin in the process of erythrocyte senescence. X-ray crystal studies of Tibetan snow leopard CNmetHb have shown that this protein crystallizes in the B state, a structure with a more open dyad, which possibly has relevance to RBC band 3 protein binding and erythrocyte senescence. R-state equine CNmetHb crystal studies elaborate the solvent differences in the switch and hinge region compared with a human deoxyhemoglobin T-­state neutron structure. Lastly, comparison of histidine protonation between the T and R state should enumerate the Bohr-effect protons.

Graphene can be obtained with the reduction of graphene oxide (GO). Various reduction methods will result in different varieties and amounts of oxygen-containing groups on the reduced graphene oxide (rGO) with diverse properties. In this work, rGO is fabricated on the titanium surfaces by the reduction process of GO through three types of reduction methods, for example, vacuum thermal annealing, hydrazine hydrate, and sodium borohydride chemical reduction. Results show that thermal annealing can remove carboxyl entirely at 600 °C for 1 h, and hydrazine hydrate can eliminate the oxygen functionalities, especially for epoxide. For sodium borohydride, it can dispose of carbonyl by converting carbonyl into hydroxyl. The rGO with different reduction process exhibits different responses for bacteria with higher numbers of carboxyl and hydroxyl/epoxide showing more effective antibacterial activities. It is concluded that carboxyl can inhibit the adhesion of bacteria on rGO surfaces by electrostatic repulsion and kill the bacteria with oxidative pressure mediated with the production of reactive oxygen species which is closely related with hydroxyl/epoxide. Furthermore, GO and rGO all exhibit excellent biocompatibility with no cytotoxicity.

The ς initiation factor ς70 of Escherichia coli acts not only in promoter recognition and DNA strand opening, but also to mediate the transformation of RNA polymerase (RNAP) to an antiterminating form by the phage λ gene Q protein. Q is able to bind and modify RNAP when α70, still present in the initially elongating enzyme, recognizes a repeat of the −10 promoter element and induces a transcription pause. We have isolated mutations in the rpoD gene for ς70 that impair Q function because they reduce the ability of ς70 to recognize the downstream pause site. These mutations identify a locus of ς70 that is important for the formation and stability of open promoter complex, likely because it mediates protein interactions with RNAP core.

e580 Background: Epidemiologic studies have reported an association between frequent consumption of well-done cooked meats and prostate cancer (PC) risk. Charred red meat and cooked processed meats are known to contain heterocyclic aromatic amine (HAA) carcinogens, such as 2-amino-1-methyl-6-phenylimidazo[4,5- b]pyridine (PhIP) the most mass abundant HAA, and are linked to PC development in a rodent model. However, unambiguous physiochemical markers of DNA damage from these meat-derived carcinogens have not been identified in human samples to support the paradigm of HAA induced human prostate carcinogenesis. Methods: Thirty-five men with biopsy proven intermediate to high-risk PC underwent radical prostatectomy at University of Minnesota from Dec 2015-Aug 2016. After prostatectomy, both tumor bearing tissue and non-tumor bearing adjacent fresh tissue was analyzed for DNA adducts using a highly sensitive nano-LC-Orbitrap mass spectrometry method. We also analyzed formalin fixed paraffin embedded (FFPE) tissues from each patient. Results: Median age of the men with PC was 65 (range 45-78). Pathology demonstrated the following Gleason Scores (GS) and pathologic staging: GS = 6 in 1 patient (2.8%), GS = 7 in 28 patients (80%) and GS = 8-10 in 6 patients (17%) and 16 men (46%) were stage 2 and 19 men were stage 3 (54%). The PhIP DNA adduct was identified in 11 out of 35 patients, at levels ranging from 2 to 120 adducts per 109 nucleotides. PhIP DNA adducts also were recovered quantitatively from FFPE tissues. Conclusions: Our data provide support to the epidemiological observations implicating PhIP as a DNA damaging agent that may contribute to the etiology of PC in humans. FFPE tissues can be used as a tissue source in DNA-adduct biomarker research using our mass spectrometry method

Noble-metal nanoparticles have had a substantial impact across a diverse range of fields, including catalysis, sensing, photochemistry, optoelectronics, energy conversion and medicine. Although silver has very desirable physical properties, good relative abundance and low cost, gold nanoparticles have been widely favoured owing to their proved stability and ease of use. Unlike gold, silver is notorious for its susceptibility to oxidation (tarnishing), which has limited the development of important silver-based nanomaterials. Despite two decades of synthetic efforts, silver nanoparticles that are inert or have long-term stability remain unrealized. Here we report a simple synthetic protocol for producing ultrastable silver nanoparticles, yielding a single-sized molecular product in very large quantities with quantitative yield and without the need for size sorting. The stability, purity and yield are substantially better than those for other metal nanoparticles, including gold, owing to an effective stabilization mechanism. The particular size and stoichiometry of the product were found to be insensitive to variations in synthesis parameters. The chemical stability and structural, electronic and optical properties can be understood using first-principles electronic structure theory based on an experimental single-crystal X-ray structure. Although several structures have been determined for protected gold nanoclusters, none has been reported so far for silver nanoparticles. The total structure of a thiolate-protected silver nanocluster reported here uncovers the unique structure of the silver thiolate protecting layer, consisting of Ag2S5 capping structures. The outstanding stability of the nanoparticle is attributed to a closed-shell 18-electron configuration with a large energy gap between the highest occupied molecular orbital and the lowest unoccupied molecular orbital, an ultrastable 32-silver-atom excavated-dodecahedral core consisting of a hollow 12-silver-atom icosahedron encapsulated by a 20-silver-atom dodecahedron, and the choice of protective coordinating ligands. The straightforward synthesis of large quantities of pure molecular product promises to make this class of materials widely available for further research and technology development.

The anomalous stability of magic-number metal clusters has been associated with closed geometric and electronic shells and the opening of HOMO-LUMO gaps. Despite this enhanced stability, magic-number clusters are known to decay and react in the condensed phase to form other products. Improving our understanding of their decay mechanisms and developing strategies to control or eliminate cluster instability is a priority, to develop a more complete theory of their stability, to avoid studying mixtures of clusters produced by the decay of purified materials, and to enable technology development. Silver clusters are sufficiently reactive to facilitate the study of the ambient temporal stability of magic-number metal clusters and to begin to understand their decay mechanisms. Here, the solution phase stability of a series of silver:glutathione (Ag:SG) clusters was studied as a function of size, pH and chemical environment. Cluster stability was found to be a non-monotonic function of size. Electrophoretic separations showed that the dominant mechanism involved the redistribution of mass toward smaller sizes, where the products were almost exclusively previously known cluster sizes. Optical absorption spectra showed that the smaller clusters evolved toward the two most stable cluster sizes. The net surface charge was found to play an important role in cluster stabilization although charge screening had no effect on stability, contrary to DLVO theory. The decay mechanism was found to involve the loss of Ag(+) ions and silver glutathionates. Clusters could be stabilized by the addition of Ag(+) ions and destabilized by either the addition of glutathione or the removal of Ag(+) ions. Clusters were also found to be most stable in near neutral pH, where they had a net negative surface charge. These results provide new mechanistic insights into the control of post-synthesis stability and chemical decay of magic-number metal clusters, which could be used to develop design principles for synthesizing specific cluster species.

Alanyl-tRNA synthetase, a dimeric class 2 aminoacyl-tRNA synthetase, activates glycine and serine at significant rates. An editing activity hydrolyzes Gly-tRNA(ala) and Ser-tRNA(ala) to ensure fidelity of aminoacylation. Analytical ultracentrifugation demonstrates that the enzyme is predominately a dimer in solution. ATP binding to full length enzyme (ARS875) and to an N-terminal construct (ARS461) is endothermic (ΔH = 3-4 kcal mol(-1)) with stoichiometries of 1:1 for ARS461 and 2:1 for full-length dimer. Binding of aminoacyl-adenylate analogues, 5'-O-[N-(L-alanyl)sulfamoyl]adenosine (ASAd) and 5'-O-[N-(L-glycinyl)sulfamoyl]adenosine (GSAd), are exothermic; ASAd exhibits a large negative heat capacity change (ΔC(p) = 0.48 kcal mol(-1) K(-1)). Modification of alanyl-tRNA synthetase with periodate-oxidized tRNA(ala) (otRNA(ala)) generates multiple, covalent, enzyme-tRNA(ala) products. The distribution of these products is altered by ATP, ATP and alanine, and aminoacyl-adenylate analogues (ASAd and GSAd). Alanyl-tRNA synthetase was modified with otRNA(ala), and tRNA-peptides from tryptic digests were purified by ion exchange chromatography. Six peptides linked through a cyclic dehydromoropholino structure at the 3'-end of tRNA(ala) were sequenced by mass spectrometry. One site lies in the N-terminal adenylate synthesis domain (residue 74), two lie in the opening to the editing site (residues 526 and 585), and three (residues 637, 639, and 648) lie on the back side of the editing domain. At least one additional modification site was inferred from analysis of modification of ARS461. The location of the sites modified by otRNA(ala) suggests that there are multiple modes of interaction of tRNA(ala) with the enzyme, whose distribution is influenced by occupation of the ATP binding site.

Bacteriophage λ gene Q protein and the related proteins of other lambdoid phages are transcription antiterminators that interact both with DNA in the late gene promoter segment and with RNA polymerase subunits. Using hybrids between Q of λ and the related Q of phage 80, we characterized elements of both Q and DNA that contribute to the DNA binding function. In particular, we found a C-terminal segment of the protein that is responsible for binding specificity and an ∼15 residue segment on a predicted alpha helix within this segment at which alanine substitutions decrease DNA binding. We identified a six-nucleotide segment located between the −35 and −10 promoter elements that confers binding specificity and is the site of point mutants that impair binding, and we isolated suppressors in λ Q that restore binding function by increasing the overall binding affinity. We also identified putative zinc finger structures in both proteins.