High-Resolution Kinoform X-Ray Optics Printed via 405 nm 3D Laser Lithography

Efficient focusing of X-rays is essential for high-resolution X-ray microscopy. Diffractive X-ray optics called kinoforms offer the highest focusing efficiencies in theory. However, they have long remained unavailable due to their challenging nanofabrication. Recently, various X-ray optic geometries including kinoforms have been realized using 3D laser lithography at near-infrared wavelengths. As the smallest features (period) of the kinoform determines the resolving power, there is a natural drive to find ways to fabricate kinoforms with ever smaller features. Here, a custom-built 3D laser lithography setup with an excitation wavelength of 405 nm is used, which allows to half the smallest period of the kinoforms compared to previous work. A 40% improvement in scanning transmission X-ray microscopy image resolution, that is, a cutoff resolution of 145 nm, and an efficiency of 7.6% at 700 eV is achieved. A reconstructed pixel size of 18.5 nm, reaching the limit imposed by the design of the microscopy set-up, is demonstrated through ptychographic imaging of a magnetic sample which has a strongly reduced contrast mechanism. Moreover, X-ray lenses manufactured by 405 nm 3D laser lithography have the potential to become much less expensive than X-ray lenses made by other means

Sestrin2 Modulates AMPK Subunit Expression and Its Response to Ionizing Radiation in Breast Cancer Cells

Background: The sestrin family of stress-responsive genes (SESN1-3) are suggested to be involved in regulation of metabolism and aging through modulation of the AMPK-mTOR pathway. AMP-activated protein kinase (AMPK) is an effector of the tumour suppressor LKB1, which regulates energy homeostasis, cell polarity, and the cell cycle. SESN1/2 can interact directly with AMPK in response to stress to maintain genomic integrity and suppress tumorigenesis. Ionizing radiation (IR), a widely used cancer therapy, is known to increase sestrin expression, and acutely activate AMPK. However, the regulation of AMPK expression by sestrins in response to IR has not been studied in depth. Methods and Findings: Through immunoprecipitation we observed that SESN2 directly interacted with the AMPKa1b1c1 trimer and its upstream regulator LKB1 in MCF7 breast cancer cells. SESN2 overexpression was achieved using a Flag-tagged SESN2 expression vector or a stably-integrated tetracycline-inducible system, which also increased AMPKa1 and AMPKb1 subunit phosphorylation, and co-localized with phosphorylated AMPKa-Thr127 in the cytoplasm. Furthermore, enhanced SESN2 expression increased protein levels of LKB1 and AMPKa1b1c1, as well as mRNA levels of LKB1, AMPKa1, and AMPKb1. Treatment of MCF7 cells with IR elevated AMPK expression and activity, but this effect was attenuated in the presence of SESN2 siRNA. In addition, elevated SESN2 inhibited IR-induced mTOR signalling and sensitized MCF7 cells to IR through an AMPK-dependent mechanism

High amp; 8208;Resolution Kinoform X Ray Optics Printed via 405 nm 3D Laser Lithography

Efficient focusing of X rays is essential for high resolution X ray microscopy. Diffractive X ray optics called kinoforms offer the highest focusing efficiencies in theory. However, they have long remained unavailable due to their challenging nanofabrication. Recently, various X ray optic geometries including kinoforms have been realized using 3D laser lithography at near infrared wavelengths. As the smallest features period of the kinoform determines the resolving power, there is a natural drive to find ways to fabricate kinoforms with ever smaller features. Here, a custom built 3D laser lithography setup with an excitation wavelength of 405 nm is used, which allows to half the smallest period of the kinoforms compared to previous work. A 40 improvement in scanning transmission X ray microscopy image resolution, that is, a cutoff resolution of 145 nm, and an efficiency of 7.6 at 700 eV is achieved. A reconstructed pixel size of 18.5 nm, reaching the limit imposed by the design of the microscopy set up, is demonstrated through ptychographic imaging of a magnetic sample which has a strongly reduced contrast mechanism. Moreover, X ray lenses manufactured by 405 nm 3D laser lithography have the potential to become much less expensive than X ray lenses made by other mean

Point defect segregation and its role in the detrimental nature of Frank partials in Cu(In,Ga)Se2 thin-film absorbers

The interaction of point defects with extrinsic Frank loops in the photovoltaic absorber material Cu(In,Ga)Se₂ was studied by aberration-corrected scanning transmission electron microscopy in combination with electron energy-loss spectroscopy and calculations based on density-functional theory. We find that Cu accumulation occurs outside of the dislocation cores bounding the stacking fault due to strain-induced preferential formation of Cu‾²In, which can be considered a harmful hole trap in Cu(In,Ga)Se₂. In the core region of the cation-containing α-core, Cu is found in excess. The calculations reveal that this is because Cu on In-sites is lowering the energy of this dislocation core. Within the Se-containing β-core, in contrast, only a small excess of Cu is observed, which is explained by the fact that Cu¡ⁿ and Cu¡ are the preferred defects inside this core, but their formation energies are positive. The decoration of both cores induces deep defect states, which enhance nonradiative recombination. Thus, the annihilation of Frank loops during the Cu(In,Ga)Se₂ growth is essential in order to obtain absorbers with high conversion efficiencies

Estimation of stature from the foot and its segments in a sub-adult female population of North India

<p>Abstract</p> <p>Background</p> <p>Establishing personal identity is one of the main concerns in forensic investigations. Estimation of stature forms a basic domain of the investigation process in unknown and co-mingled human remains in forensic anthropology case work. The objective of the present study was to set up standards for estimation of stature from the foot and its segments in a sub-adult female population.</p> <p>Methods</p> <p>The sample for the study constituted 149 young females from the Northern part of India. The participants were aged between 13 and 18 years. Besides stature, seven anthropometric measurements that included length of the foot from each toe (T1, T2, T3, T4, and T5 respectively), foot breadth at ball (BBAL) and foot breadth at heel (BHEL) were measured on both feet in each participant using standard methods and techniques.</p> <p>Results</p> <p>The results indicated that statistically significant differences (p < 0.05) between left and right feet occur in both the foot breadth measurements (BBAL and BHEL). Foot length measurements (T1 to T5 lengths) did not show any statistically significant bilateral asymmetry. The correlation between stature and all the foot measurements was found to be positive and statistically significant (<it>p-value </it>< 0.001). Linear regression models and multiple regression models were derived for estimation of stature from the measurements of the foot. The present study indicates that anthropometric measurements of foot and its segments are valuable in the estimation of stature. Foot length measurements estimate stature with greater accuracy when compared to foot breadth measurements.</p> <p>Conclusions</p> <p>The present study concluded that foot measurements have a strong relationship with stature in the sub-adult female population of North India. Hence, the stature of an individual can be successfully estimated from the foot and its segments using different regression models derived in the study. The regression models derived in the study may be applied successfully for the estimation of stature in sub-adult females, whenever foot remains are brought for forensic examination. Stepwise multiple regression models tend to estimate stature more accurately than linear regression models in female sub-adults.</p

145 Characterization of adverse reactions in patients with advanced endometrial cancer (aec) receiving lenvatinib + pembrolizumab (Study 309/KEYNOTE-775)

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DMSO and Betaine Greatly Improve Amplification of GC-Rich Constructs in De Novo Synthesis

In Synthetic Biology, de novo synthesis of GC-rich constructs poses a major challenge because of secondary structure formation and mispriming. While there are many web-based tools for codon optimizing difficult regions, no method currently exists that allows for potentially phenotypically important sequence conservation. Therefore, to overcome these limitations in researching GC-rich genes and their non-coding elements, we explored the use of DMSO and betaine in two conventional methods of assembly and amplification. For this study, we compared the polymerase (PCA) and ligase-based (LCR) methods for construction of two GC-rich gene fragments implicated in tumorigenesis, IGF2R and BRAF. Though we found no benefit in employing either DMSO or betaine during the assembly steps, both additives greatly improved target product specificity and yield during PCR amplification. Of the methods tested, LCR assembly proved far superior to PCA, generating a much more stable template to amplify from. We further report that DMSO and betaine are highly compatible with all other reaction components of gene synthesis and do not require any additional protocol modifications. Furthermore, we believe either additive will allow for the production of a wide variety of GC-rich gene constructs without the need for expensive and time-consuming sample extraction and purification prior to downstream application

The p21-Dependent Radiosensitization of Human Breast Cancer Cells by MLN4924, an Investigational Inhibitor of NEDD8 Activating Enzyme

Radiotherapy is a treatment choice for local control of breast cancer. However, intrinsic radioresistance of cancer cells limits therapeutic efficacy. We have recently validated that SCF (SKP1, Cullins, and F-box protein) E3 ubiquitin ligase is an attractive radiosensitizing target. Here we tested our hypothesis that MLN4924, a newly discovered investigational small molecule inhibitor of NAE (NEDD8 Activating Enzyme) that inactivates SCF E3 ligase, could act as a novel radiosensitizing agent in breast cancer cells. Indeed, we found that MLN4924 effectively inhibited cullin neddylation, and sensitized breast cancer cells to radiation with a sensitivity enhancement ratio (SER) of 1.75 for SK-BR-3 cells and 1.32 for MCF7 cells, respectively. Mechanistically, MLN4924 significantly enhanced radiation-induced G2/M arrest in SK-BR-3 cells, but not in MCF7 cells at early time point, and enhanced radiation-induced apoptosis in both lines at later time point. However, blockage of apoptosis by Z-VAD failed to abrogate MLN4924 radiosensitization, suggesting that apoptosis was not causally related. We further showed that MLN4924 failed to enhance radiation-induced DNA damage response, but did cause minor delay in DNA damage repair. Among a number of tested SCF E3 substrates known to regulate growth arrest, apoptosis and DNA damage response, p21 was the only one showing an enhanced accumulation in MLN4924-radiation combination group, as compared to the single treatment groups. Importantly, p21 knockdown via siRNA partialy inhibited MLN4924-induced G2/M arrest and radiosensitization, indicating a causal role played by p21. Our study suggested that MLN4924 could be further developed as a novel class of radiosensitizer for the treatment of breast cancer