Damage Spots Research Articles

Comparison of K-Ras and N-Ras Mutagenic Hot Spots for UVC Damage.

It has been well established that mutations in K-Ras and N-Ras proto-oncogenes can convert them into active oncogenes. Current molecular cancer research has been focused on determining the key steps by which cellular genes become oncogenes and not on the underlying and fundamental chemical damage mechanism and susceptibility to damage. In this study, we investigate the damage hot spots present in the N-Ras and K-Ras genes upon exposure to UVC radiation. Detection of damage is accomplished by a simple, sensitive, mix-and-read assay using an EvaGreen probe in a 96-well microtiter plate. Our results show that, although there is high degree of sequential similarities among K-Ras and N-Ras genes, they show different degrees of UV damage in different portions of their genomes. Our experiments demonstrate that overall, the K-Ras genome is more prone to UVC damage than the N-Ras genome. We observe that the extent of damage increases with increasing number of TTs in a sequence, consistent with previous results that show that thymine cyclobutyl photodimers are the primary DNA damage photoproducts upon UVC irradiation. This understanding of the effect of UVC radiation on various codons of K-Ras and N-Ras genes will help to increase our understanding about hot spots of DNA damage and the chemical damage mechanism.

Increased TFAM binding to mtDNA damage hot spots is associated with mtDNA loss in aged rat heart

The well-known age-related mitochondrial dysfunction deeply affects heart because of the tissue's large dependence on mitochondrial ATP provision. Our study revealed in aged rat heart a significant 25% decrease in mtDNA relative content, a significant 29% increase in the 4.8 Kb mtDNA deletion relative content, and a significant inverse correlation between such contents as well as a significant 38% decrease in TFAM protein amount. The TFAM-binding activity to specific mtDNA regions increased at those encompassing the mtDNA replication origins, D-loop and Ori-L. The same mtDNA regions were screened for different kinds of oxidative damage, namely Single Strand Breaks (SSBs), Double Strand Breaks (DSBs), abasic sites (AP sites) and oxidized bases as 7,8-dihydro-8-oxoguanine (8oxoG). A marked increase in the relative content of mtDNA strand damage (SSBs, DSBs and AP sites) was found in the D-loop and Ori-L regions in the aged animals, unveiling for the first time in vivo an age-related, non-stochastic accumulation of oxidative lesions in these two regions that appear as hot spots of mtDNA damage. The use of Formamidopyrimidine glycosylase (Fpg) demonstrated also a significant age-related accumulation of oxidized purines particularly in the D-loop and Ori-L regions. The detected increased binding of TFAM to the mtDNA damage hot spots in aged heart suggests a link between TFAM binding to mtDNA and loss of mitochondrial genome likely through hindrance of repair processes.

1173 Inducible DNA repair of UV photoproducts depends on vitamin D receptor

Ultraviolet radiation (UV) initiates vitamin D synthesis by converting 7-dehydrocholesterol to pre-vitamin D3 that is converted to 25-hydroxyvitamin D3 (25D3) and then 1,25-dihydroxyvitamin D3 (1,25D3). However, UV also generates DNA damage that is repaired by nucleotide excision repair (NER). We tested the hypothesis that vitamin D signaling elicits compensatory responses to the DNA damage incurred during vitamin D synthesis. Treatment of human keratinocytes with either UVB or with 1,25D3 or 25D3 induced the DNA damage recognition protein, XPC, and induction was suppressed by either siRNA targeting the vitamin D receptor (VDR) or ketoconazole, a broad inhibitor of oxidases that hydroxylate vitamin D3 to active metabolites. Irradiation of cells with UVC through 3 um pore filters resulted in sub-nuclear spots of DNA damage that were probed with antibodies to the major UV-induced DNA lesions, and to XPC. Relative to controls which removed >50% of 6-4 photoproduct (6-4PP) spots and reduced spot intensity by >70% over 2 hours, cells treated with siRNA targeting VDR had no significant change in either spot density or intensity over this time period (p<0.001), indicating a lack of NER. Co-staining of spots for XPC demonstrated that XPC begins accumulating at DNA damage spots within seconds, peaking by 15 minutes following UV damage, and was no longer detectable at DNA damage spots by 90 minutes, consistent with rapid 6-4PP repair. In contrast, siVDR-treated cells, while also rapidly recruiting XPC to 6-4PP, exhibited prolonged retention of XPC at 6-4PP spots at 30 minutes relative to controls. These results indicate that vitamin D and VDR are important for both induction of XPC as well as normal retention of XPC at DNA damage in keratinocytes, and suggest that vitamin D may mitigate the UV-induced DNA damage associated with its own genesis.

Structural Health Monitoring in Composite Structures by Fiber-Optic Sensors.

Fiber-optic sensors cannot measure damage; to get information about damage from strain measurements, additional strategies are needed, and several alternatives are available in the existing literature. This paper discusses two independent procedures. The first is based on detecting new strains appearing around a damage spot. The structure does not need to be under loads, the technique is very robust, and damage detectability is high, but it requires sensors to be located very close to the damage, so it is a local technique. The second approach offers wider coverage of the structure; it is based on identifying the changes caused by damage on the strain field in the whole structure for similar external loads. Damage location does not need to be known a priori, and detectability is dependent upon the sensor’s network density, the damage size, and the external loads. Examples of application to real structures are given.

Crystal growth, structural, optical, thermal and dielectric properties of lithium hydrogen oxalate monohydrate single crystal

The vibrational groups of the lithium hydrogen oxalate monohydrate have been investigated by FTIR and FT- Raman analyses. It has low absorbance in the UV-Vis-NIR region. The laser damage threshold study confirms that the material withstands upto 30 mJ with time of 7 s, after that circular dot damage is seen on the surface. The dark region of the surface damage spot occurs due to the thermal effects. The material is thermally stable upto 93 °C and there is no weight loss below this temperature. The dielectric studies were carried out at the frequency regions of 1 kHz–1 MHz and different temperatures from 40 °C to 80 °C. Semi-organic non-linear optical (NLO) single crystal lithium hydrogen oxalate monohydrate has been grown by slow evaporation solution growth technique. The Hirshfeld surface analysis was performed to understand the different intermolecular interactions in the title compound. The fingerprint plots contain the highest portion of H⋯O/O⋯H (48.3%) interactions.

An enhanced energy vibration-based approach for damage detection and localization

This paper addresses the enhanced identification and localization of structural damage by means of the recorded response induced by ambient excitation. Damage detection is based purely on the vibration energy in structural acceleration records, deriving thereof the normalized cumulative power spectral density as the characteristic damage sensitive quantity. As key aspect of this contribution, a method for “correction” of the recorded response is proposed, to account for deviations from perfect stationary white noise excitation. Based on an overdetermined system of equations, recorded spectra are modified to better fit previously recorded spectra. This fitting affects broader frequency ranges, while the damage sensitive feature captures changes in narrow frequency bands. Thus, the proposed “correction” method does not mask or remove the effects of structural changes in the response. Subsequent damage localization in cantilever-like structures is based on the changes of the drift of the fundamental mode shape amplitudes. The efficiency of the proposed two-step damage identification procedure is tested on a small-scale shear frame model in various damaged conditions. It is shown that the defined normalized cumulative power spectral density damage index is suitable to indicate most of the imposed damages, in particular when the proposed response correction methodology is applied. The spots of damage are successfully identified by the utilized mode shape damage indicator.

Ocular damage effects from 1338-nm pulsed laser radiation in a rabbit eye model.

The ocular damage effects induced by transitional near-infrared (NIR) lasers have been investigated for years. However, no retinal damage thresholds are determined in a wide interval between 0.65 ms and 80 ms, and a definite relationship between corneal damage threshold and spot size cannot be drawn from existing data points. In this paper, the in-vivo corneal damage thresholds (ED50s) were determined in New Zealand white rabbits for a single 5 ms pulse at the wavelength of 1338 nm for spot sizes from 0.28 mm to 3.55 mm. Meanwhile, the retinal damage threshold for this laser was determined in chinchilla grey rabbits under the condition that the beam was collimated, and the incident corneal spot diameter was 5.0 mm. The corneal ED50s given in terms of the corneal radiant exposure for spot diameters of 0.28, 0.94, 1.91, and 3.55 mm were 70.3, 35.6, 29.6 and 30.3 J/cm2, respectively. The retinal ED50 given in terms of total intraocular energy (TIE) was 0.904 J. The most sensitive ocular tissue to this laser changed from the cornea to retina with the increase of spot size.

Building dampness and mold in European homes in relation to climate, building characteristics and socio-economic status: The European Community Respiratory Health Survey ECRHS II.

We studied dampness and mold in homes in relation to climate, building characteristics and socio-economic status (SES) across Europe, for 7127 homes in 22 centers. A subsample of 3118 homes was inspected. Multilevel analysis was applied, including age, gender, center, SES, climate, and building factors. Self-reported water damage (10%), damp spots (21%), and mold (16%) in past year were similar as observed data (19% dampness and 14% mold). Ambient temperature was associated with self-reported water damage (OR=1.63 per 10°C; 95% CI 1.02-2.63), damp spots (OR=2.95; 95% CI 1.98-4.39), and mold (OR=2.28; 95% CI 1.04-4.67). Precipitation was associated with water damage (OR=1.12 per 100mm; 95% CI 1.02-1.23) and damp spots (OR=1.11; 95% CI 1.02-1.20). Ambient relative air humidity was not associated with indoor dampness and mold. Older buildings had more dampness and mold (P<.001). Manual workers reported less water damage (OR=0.69; 95% CI 0.53-0.89) but more mold (OR=1.27; 95% CI 1.03-1.55) as compared to managerial/professional workers. There were correlations between reported and observed data at center level (Spearman rho 0.61 for dampness and 0.73 for mold). In conclusion, high ambient temperature and precipitation and high building age can be risk factors for dampness and mold in homes in Europe.

Study of grain-level deformation and residual stresses in Ti-7Al under combined bending and tension using high energy diffraction microscopy (HEDM)

In-situ high energy diffraction microscopy (HEDM) experiments are carried out to analyze the state of combined bending and tension in a Ti-7Al alloy under room temperature creep. Grain-level elastic strain tensors are evaluated from HEDM data. Atomistic calculations are used to predict elastic constants of Ti-7Al, to be used in determination of stress from strain. The stress gradient and residual stresses are successfully determined, which allows the demarcation between macro-/micro-level residual stresses. A cluster of three neighboring grains are identified that highlight the variation of mean and effective stress between grains. Crystallographic orientations and slip characteristics are analyzed for the selected grains. It is inferred that the interfaces between loaded grains with markedly different stress triaxiality and slip tendency are potential spots for material damage.

Geographic analysis of earthquake damage in Turkey between 1900 and 2012

ABSTRACTThis study investigates the relationship between fatality and magnitude, energy released, time of earthquake occurrence and building damage, and between building damage and magnitude and energy of earthquakes that occurred in Turkey between 1900 and 2012. Patterns of earthquake occurrence and damage are examined across space and time. Ninety-one per cent and eighty-three per cent of the variation in fatality and building damage are accounted for by the energy released from an earthquake, respectively. Building damage explains 85% of the variation in fatality. Seventy-six per cent of the total death toll is a result of the earthquakes that happened between midnight and 5:22 am. There were two significant clusters of earthquakes in Western Turkey between 1955 and 1965 and between 1969 and 1971. Provinces of Erzincan and Kocaeli emerge as hot spots of fatality and building damage. The location of major earthquakes over 112 years tends to parallel the tectonically active areas of Turkey such as the North and East Anatolian Faults and Western Turkey towards the Aegean Sea. Central, central south, extreme north-western, north-eastern and south-eastern Turkey appears to be void of major earthquakes.

Valosin-containing Protein (VCP)/p97 Segregase Mediates Proteolytic Processing of Cockayne Syndrome Group B (CSB) in Damaged Chromatin

Cockayne syndrome group A and B (CSB) proteins act in transcription-coupled repair, a subpathway of nucleotide excision repair. Here we demonstrate that valosin-containing protein (VCP)/p97 segregase functions in ultraviolet radiation (UVR)-induced ubiquitin-mediated CSB degradation. We show that VCP/p97 inhibition and siRNA-mediated ablation of VCP/p97 and its cofactors UFD1 and UBXD7 impair CSB degradation. VCP/p97 inhibition also results in the accumulation of CSB in chromatin. Moreover, VCP/p97 interacts with both native and ubiquitin-conjugated forms of CSB. The localized cellular UVR exposures lead to VCP/p97 accumulation at DNA damage spots, forming distinct UVR-induced foci. However, manifestation of VCP/p97 foci is independent of CSB and UBXD7. Furthermore, VCP/p97 and UBXD7 associate with the Cockayne syndrome group A-DDB1-Cul4A complex, an E3 ligase responsible for CSB ubiquitination. Compromising proteasome and VCP/p97 function allows accumulation of both native and ubiquitinated CSB and results in an increase of UBXD7, proteasomal RPN2, and Sug1 in the chromatin compartment. Surprisingly, both biochemical inhibition and genetic defect of VCP/p97 enhance the recovery of RNA synthesis following UVR, whereas both VCP/p97 and proteasome inhibitions decrease cell viability. Our findings reveal a new role of VCP/p97 segregase in the timely processing of ubiquitinated CSB from damaged chromatin.

A Statistical Theory of the Damage of Materials

A statistical theory of disperse damage of materials gained under loading is proposed. It is based on the idea of distribution of potential damage spots within a specimen similar to the distribution of the strength values found by testing a set of identical specimens. A relation between damage risk and the probability of damage of a single specimen is assumed. It conforms to the relation between risk and probability of strength distribution of a set of identical specimens, according to Weibull’s statistical theory of material strength. The damage risk just like the damage probability are assumed to be functions of loading and time. Damage is modeled regarding two mechanisms—thermo-fluctuation damage based on the kinetic theory of material strength, and damage depending on a parameter called loading degree (percentage), which depends on load and time. The first mechanism adopts two relations regarding energy barrier reduction due to loading. Equations of damage advance under short-term loading (with a constant rate of load increase) and under long-term (constant) loading are derived. Theoretical relations of damage development are compared with experimental evidence gained via specific tests on short glass fibre reinforced polyoximethylene. The damage itself consists of the accumulation of additional internal surfaces within the entire material volume as measured by small angle scattering X-ray refractometry. It is shown that the mechanism of damage as a function of loading degree where time participates implicitly, gains advantage over the kinetic mechanism where time is explicitly present. The cumulative functions derived for damage accumulation can be used to assess not only damage, but also for statistical analysis of the strength and other quantities.

Surface phase defects induced downstream laser intensity modulation in high-power laser facility

Optics surface phase defects induced intensity modulation in high-power laser facility for inertial confinement fusion research is studied. Calculations and experiments reveal an exact mapping of the modulation patterns and the optics damage spot distributions from the surface phase defects. Origins are discussed during the processes of optics manufacturing and diagnostics, revealing potential improvements for future optics manufacturing techniques and diagnostic index, which is meaningful for fusion level laser facility construction and its operation safety.

Optical damage as a computer generated hologram recording mechanism

Abstract In this paper we report optical damage as a bulk glass recording process. We used a 10 Hz, 35 picoseconds, 5 mJ polarized Nd:YAG pulse laser focused using a 25 mm lens to create 50 μm average optical damage spots to record a computer generated hologram embedded in stress free BK-7 glass. It was observed that for the recording conditions the material surrounding the damage spot was induced birefringence altered producing a 70 μm pixel optimal separation.

Crime and the NTE: multi-classification crime (MCC) hot spots in time and space

This paper examines crime hot spots near licensed premises in the night-time economy (NTE) to investigate whether hot spots of four different classification of crime and disorder co-occur in time and place, namely violence, disorder, drugs and criminal damage. It introduces the concept of multi-classification crime (MCC) hot spots; the presence of hot spots of more than one crime classification at the same place. Furthermore, it explores the temporal patterns of identified MCC hot spots, to determine if they exhibit distinct spatio-temporal patterns. Getis Ord (GI*) hot spot analysis was used to identify locations of statistically significant hot spots of each of the four crime and disorder classifications. Strong spatial correlations were found between licensed premises and each of the four crime and disorder classifications analysed. MCC hot spots were also identified near licensed premises. Temporal profiling of the MCC hot spots revealed all four crime types were simultaneously present in time and place, near licensed premises, on Friday through Sunday in the early hours of the morning around premise closing times. At other times, criminal damage and drugs hot spots were found to occur earlier in the evening, and disorder and violence at later time periods. Criminal damage and drug hot spots flared for shorter time periods, 2–3 h, whereas disorder and violence hot spots were present for several hours. There was a small spatial lag between Friday and Saturday, with offences occurring approximately 1 h later on Saturdays. The implications of these findings for hot spot policing are discussed.

Laser induced periodic surface structure formation in germanium by strong field mid IR laser solid interaction at oblique incidence.

Laser induced periodic surface structures (LIPSS or ripples) were generated on single crystal germanium after irradiation with multiple 3 µm femtosecond laser pulses at a 45° angle of incidence. High and low spatial frequency LIPSS (HSFL and LSFL, respectively) were observed for both s- and p-polarized light. The measured LSFL period for p-polarized light was consistent with the currently established LIPSS origination model of coupling between surface plasmon polaritons (SPP) and the incident laser pulses. A vector model of SPP coupling is introduced to explain the formation of s-polarized LSFL away from the center of the damage spot. Additionally, a new method is proposed to determine the SPP propagation length from the decay in ripple depth. This is used along with the measured LSFL period to estimate the average electron density and Drude collision time of the laser-excited surface. Finally, full-wave electromagnetic simulations are used to corroborate these results while simultaneously offering insight into the nature of LSFL formation.

Damaged DNA-binding protein down-regulates epigenetic mark H3K56Ac through histone deacetylase 1 and 2

Acetylated histone H3 lysine 56 (H3K56Ac) is one of the reversible histone post-translational modifications (PTMs) responsive to DNA damage. We previously described a biphasic decrease and increase of epigenetic mark H3K56Ac in response to ultraviolet radiation (UVR)-induced DNA damage. Here, we report a new function of UV damaged DNA-binding protein (DDB) in deacetylation of H3K56Ac through specific histone deacetylases (HDACs). We show that simultaneous depletion of HDAC1/2 compromises the deacetylation of H3K56Ac, while depletion of HDAC1 or HDAC2 alone has no effect on H3K56Ac. The H3K56Ac deacetylation does not require functional nucleotide excision repair (NER) factors XPA and XPC, but depends on the function of upstream factors DDB1 and DDB2. UVR enhances the association of DDB2 with HDAC1 and, enforced DDB2 expression leads to translocation of HDAC1 to UVR-damaged chromatin. HDAC1 and HDAC2 are recruited to UVR-induced DNA damage spots, which are visualized by anti-XPC immunofluorescence. Dual HDAC1/2 depletion decreases XPC ubiquitination, but does not affect the recruitment of DDB2 to DNA damage. By contrast, the local accumulation of γH2AX at UVR-induced DNA damage spots was compromised upon HDAC1 as well as dual HDAC1/2 depletions. Additionally, UVR-induced ATM activation decreased in H12899 cells expressing H3K56Ac-mimicing H3K56Q. These results revealed a novel role of DDB in H3K56Ac deacetylation during early step of NER and the existence of active functional cross-talk between DDB-mediated damage recognition and H3K56Ac deacetylation.

SG-II-Up prototype final optics assembly: optical damage and clean-gas control

The Shenguang-II Upgrade (SG-II Up) facility is an under-construction high-power laser driver with eight beams, 24 kJ energy, 3 ns pulse duration and ultraviolet laser output, in the Shanghai Institute of Optics and Fine Mechanics, China. The prototype design and experimental research of the prototype final optics assembly (FOA), which is one of the most important parts of the SG-II Up facility, have been completed on the ninth beam of the SG-II facility. Thirty-three shots were fired using 1- ${\it\omega}$ energy from 1000 to 4500 J and 3- ${\it\omega}$ energy from 500 to 2403 J with a 3 ns square pulse. During the experiments, emphasis was given to the process of optical damage and to the effects of clean-gas control. A numerical model of the FOA generated by the Integrated Computer Engineering and Manufacturing code for Computational Fluid Dynamics (ICEMCFD) demonstrated that a flux within $1{-}5~\text{l s}^{-1}$ and a 180 s period is effectual to avoid contaminant sputtering to the optics. The presence of surface ‘mooning’ damage and surface spots located outside the clear aperture are induced by contaminants such as wire, silica gel and millimeter order fiber and metal.

A Novel Solar Simulator Based on a Supercontinuum Laser for Solar Cell Device and Materials Characterization

The design, operation, and application of a novel solar simulator based on a high-power supercontinuum fiber laser are described. The simulator features a multisun irradiance with continuous spectral coverage from the visible to the infrared. By use of a prism-based spectral shaper, the simulator can be matched to any desired spectral profile, including the ASTM G-173-03 air-mass 1.5 reference spectrum. The simulator was used to measure the efficiency of gallium arsenide (GaAs), crystalline silicon (Si), amorphous Si, and copper-indium-gallium-selenide (CIGS) thin-film solar cells, showing agreement with independent measurements. The pulsed temporal characteristic of the simulator was studied and would appear to have a negligible influence on measured cell efficiency. The simulator light was focused to a spot of approximately 8 μm in diameter and used to create micrometer-scale spatial maps of full spectrum optical-beam-induced current. Microscopic details such as grid lines, damage spots, and material variations were selectively excited and resolved on GaAs and CIGS cells. The spectral shaping capabilities were used to create output spectra appropriate for selectively light-biasing multijunction cell layers. The simulator was used to create variable blue-rich and red-rich spectra that were applied to a GaInP/GaAs tandem solar cell to illustrate the current-limiting behavior.

Interface characteristics of peeling-off damages of laser coatings

Coating stacks of HfO2/SiO2 and Ta2O5/SiO2 were separately prepared by electron beam evaporation and dual ion beam sputtering. Damage characteristics at the interlayer interfaces were analyzed after irradiation of the coatings by a 1064nm laser. The cross-sectional morphologies of damage spots indicated that peeling-off damages always occurred at the interface where the low refractive index material (SiO2) was deposited on the high refractive index material (HfO2 or Ta2O5). The effects of interface microstructure and components on peeling-off damages were also discussed. The microstructure of the interface was not a major factor that influenced peeling-off damages. Incomplete oxides (SiOx) and Na, K, Li ions accumulated near the interface and caused the formation of micro-defects layers with nano-sized thicknesses. Micro-defects layers maybe reduced adhesion of different interfaces and formed plasmas by absorbing laser energy. Finally stripping damages happened from micro-defects layers during irradiation by a 1064nm laser.