First-Principles High-Throughput Study of Linear and Nonlinear Optical Materials

Nonlinear optical (NLO) processes, such as second harmonic generation (SHG), play an important role in modern optics, especially in laser-related science and technology. They are at the core of a wide variety of applications ranging from optoelectronics to medicine. Among the various NLO materials, insulators are particularly important for second-order NLO properties. In particular, only crystals which are non-centrosymmetric can display a non-zero second-order NLO susceptibility. However, given the large number of requirements that a material needs to meet in order to be a good nonlinear optical material, the choice of compounds is drastically limited. Indeed, despite recent progress, a systematic approach to design NLO materials is still lacking. In this work, we conduct a first-principles high-throughput study on a large set of semiconductors for which we computed the linear and nonlinear susceptibility using Density Functional Perturbation Theory. For the linear optical properties, our calculations confirm the general trend that the refractive index is roughly inversely proportional to the band gap. In order to explain the large spread in the data distribution, we have found that two descriptors successfully describe materials with relatively high refraction index: (i) a narrow distribution in energy of the optical transitions which brings the average optical gap close to the direct band gap (ii) a large number of transitions around the band edge and/or high dipole matrix elements. For non-centrosymmetric crystals, we perform the calculation of the efficiency of SHG. We observe some materials with particularly high SHG, much stronger than the general relation with the linear refraction index through Miller’s rule predicts. We relate the value of Miller’s coefficient to geometric factors, i.e., how strongly the crystal deviates from a centrosymmetric one. We also identified interesting materials that show high optical responses for which it would be worth performing further analysis

Searching for Materials with High Refractive Index and Wide Band Gap: A First-Principles High-Throughput Study

Materials combining both a high refractive index and a wide band gap are of great interest for optoelectronic and sensor applications. However, these two properties are typically described by an inverse correlation with high refractive index appearing in small gap materials and vice-versa. Here, we conduct a first-principles high-throughput study on more than 4000 semiconductors (with a special focus on oxides). Our data confirm the general inverse trend between refractive index and band gap but interesting outliers are also identified. The data are then analyzed through a simple model involving two main descriptors: the average optical gap and the effective frequency. The former can be determined directly from the electronic structure of the compounds, but the latter cannot. This calls for further analysis in order to obtain a predictive model. Nonetheless, it turns out that the negative effect of a large band gap on the refractive index can counterbalanced in two ways: (i) by limiting the difference between the direct band gap and the average optical gap which can be realized by a narrow distribution in energy of the optical transitions and (ii) by increasing the effective frequency which can be achieved through either a high number of transitions from the top of the valence band to the bottom of the conduction or a high average probability for these transitions. Focusing on oxides, we use our data to investigate how the chemistry influences this inverse relationship and rationalize why certain classes of materials would perform better. Our findings can be used to search for new compounds in many optical applications both in the linear and non-linear regime (waveguides, optical modulators, laser, frequency converter, etc.).Comment: The manuscript is made of 10 pages with 6 figures and 1 table. At the end of the main text, there is an appendix with 2 figures. Supplemental material includes 7 figures and 6 tables. In the db.csv file there are the materials properties we computed in this wor

Endothelial Function and Dipper Status

SUMMARY Aims: Essential hypertension, as well as other established cardiovascular risk factors, is associated with endothelial dysfunction. Hypertensive patients with a nondipper circadian pattern have a greater risk of cerebrovascular and cardiovascular complications in comparison with those with a dipper circadian pattern. In this study, we evaluated the association between nondipper pattern and endothelial function in patients with essential hypertension. Methods: We evaluated the forearm blood flow (FBF) response to intraarterial acetylcholine (ACh), an endothelium-dependent vasodilator, and sodium nitroprusside (SNP), an endothelium-independent vasodilator, infusions in 190 hypertensive patients stratified according to dipper and nondipper status. The FBF was measured by strain-gauge plethysmography. Effects of oxidative stress on FBF were evaluated by intraarterial infusion of vitamin C. Ambulatory BP monitorings were obtained by a validated oscillometric device (SpaceLabs 90207 Monitor Inc., Issaquah, WA, USA). Results: Systolic and diastolic blood pressures were higher during daytime and lower during night-time in dipper subjects than in nondippers. The peak percent increase in ACh-stimulated FBF was higher in dippers than in nondippers (473% vs. 228%, P < 0.001). The FBF responses to SNP were similar in dipper and nondipper patients. The FBF response to ACh during coinfusion of vitamin C was higher in nondippers rather than in dipper hypertensives. Conclusions: Present data demonstrate that endothelium-dependent vasodilation is impaired in patients who have nondipper hypertension. The effects of vitamin C on impaired ACh-stimulated vasodilation support the hypothesis that oxidative stress contributes to endothelial dysfunction of nondipper hypertensive patients

Platelet aggregation is affected by nitrosothiols in patients with chronic hepatitis: in vivo and in vitro studies

AIM: To investigate the relationship among the number of platelets and plasma levels of S-nitrosothiols (S-NO), nitrite, total non-protein SH (NPSH), glutathione (GSH), cysteine (CYS), malondialdehyde (MDA), 4-hydroxininenal (4HNE), tumor necrosis factor-alpha (TNFalpha) and interleukin (IL)-6 in patients with chronic hepatitis C (CH). METHODS: In vitro the aggregation of platelets derived from controls and CH patients was evaluated before and after the addition of adenosine diphosphate (ADP) and collagen, both in basal conditions and after incubation with nitrosoglutathione (GSNO). RESULTS: In vivo, S-NO plasma levels increased significantly in CH patients and they were significantly directly correlated with platelet numbers. Patients with platelet counts 150000/microL. In vitro, the ADP and collagen aggregation time was increased in platelets from patients and not from controls; in addition, platelets from CH patients but not from controls also showed a latency time after exposure to collagen

Investigating molecular alterations to profile short- and long-term recurrence-free survival in patients with primary glioblastoma

Glioblastoma (GB) is the most aggressive type of primary brain tumor. Despite the progress in recent years regarding the diagnosis and treatment of GB, the recurrence rate remains high, due to the infiltrative and dispersive nature of the tumor, which typically results in poor patient prognosis. In the present study, 19 formalin-fixed, paraffin-embedded GB samples were selected from patients with GB tumors. The samples were classified into a short or long recurrence-free survival (RFS) group, based on the time of first recurrence of the disease in the patients. The 19 samples were molecularly characterized for mutations in the isocitrate dehydrogenase 1 (IDH1) gene, amplification of the epidermal growth factor receptor (EGFR) gene, presence of the EGFR variant III, and methylation of the promoter region of the O6-methylguanine-DNA methyltransferase (MGMT) gene. Then, the expression of 84 genes involved in cell-cell and cell-matrix interactions, and that of 84 microRNAs (miRNAs) associated with brain cancer, was profiled. In addition, a copy number variation analysis of 23 genes reported to undergo frequent genomic alterations in human glioma was also performed. Differences in the expression levels of a number of genes were detected across the short and long RFS groups. Among these genes, 5 in particular were selected, and a 5-genes combination approach was developed, which was able to differentiate between patients with short and long RFS outcome. The high levels of sensitivity and precision displayed by this 5-genes combination approach, which were confirmed with a cross-validation method, provide a strong foundation for further validation of the involvement of the aforementioned genes in GB in a larger patient population. In conclusion, the present study has demonstrated how the expression pattern of miRNAs and mRNAs in patients with GB defines a particular molecular hallmark that may increase or reduce the aggressive behavior of GB tumors, thus influencing the survival rates of patients with GB, their response to therapy and their tendency to suffer a relapse

Second-harmonic generation tensors from high-throughput density-functional perturbation theory

peer reviewedOptical materials play a key role in enabling modern optoelectronic technologies in a wide variety of domains such as the medical or the energy sector. Among them, nonlinear optical crystals are of primary importance to achieve a broader range of electromagnetic waves in the devices. However, numerous and contradicting requirements significantly limit the discovery of new potential candidates, which, in turn, hinders the technological development. In the present work, the static nonlinear susceptibility and dielectric tensor are computed via density-functional perturbation theory for a set of 579 inorganic semiconductors. The computational methodology is discussed and the provided database is described with respect to both its data distribution and its format. Several comparisons with both experimental and ab initio results from literature allow to confirm the reliability of our data. The aim of this work is to provide a relevant dataset to foster the identification of promising nonlinear optical crystals in order to motivate their subsequent experimental investigation

Cancer astrocytes have a more conserved molecular status in long recurrence free survival (RFS) IDH1 wild-type glioblastoma patients: New emerging cancer players

Glioblastoma is a devastating disease that despite all the information gathered so far, its optimal management remains elusive due to the absence of validated targets from clinical studies. A better clarification of the molecular mechanisms is needed. In this study, having access to IDH1 wild-type glioblastoma of patients with exceptionally long recurrence free survival (RFS), we decided to compare their mutational and gene expression profile to groups of IDH1 wild-type glioblastoma of patients with shorter RFS, by using NGS technology. The exome analysis revealed that Long-RFS tumors have a lower mutational rate compared to the other groups. A total of 158 genes were found differentially expressed among the groups, 112 of which distinguished the two RFS extreme groups. Overall, the exome data suggests that shorter RFS tumors could be, chronologically, in a more advanced state in the muli-step tumor process of sequential accumulation of mutations. New players in this kind of cancer emerge from the analysis, confirmed at the RNA/DNA level, identifying, therefore, possible oncodrivers or tumor suppressor genes

Multiregional sequencing of IDH-WT glioblastoma reveals high genetic heterogeneity and a dynamic evolutionary history

Glioblastoma is one of the most common and lethal primary neoplasms of the brain. Patient survival has not improved significantly over the past three decades and the patient median survival is just over one year. Tumor heterogeneity is thought to be a major determinant of therapeutic failure and a major reason for poor overall survival. This work aims to comprehensively define intra- and inter-tumor heterogeneity by mapping the genomic and mutational landscape of multiple areas of three primary IDH wild-type (IDH-WT) glioblastomas. Using whole exome sequencing, we explored how copy number variation, chromosomal and single loci amplifications/deletions, and mutational burden are spatially distributed across nine different tumor regions. The results show that all tumors exhibit a different signature despite the same diagnosis. Above all, a high inter-tumor heterogeneity emerges. The evolutionary dynamics of all identified mutations within each region underline the questionable value of a single biopsy and thus the therapeutic approach for the patient. Multiregional collection and subsequent sequencing are essential to try to address the clinical challenge of precision medicine. Especially in glioblastoma, this approach could provide powerful support to pathologists and oncologists in evaluating the diagnosis and defining the best treatment option

Metabolic-imaging of human glioblastoma live tumors: A new precision-medicine approach to predict tumor treatment response early

Glioblastoma (GB) is the most severe form of brain cancer, with a 12-15 month median survival. Surgical resection, temozolomide (TMZ) treatment, and radiotherapy remain the primary therapeutic options for GB, and no new therapies have been introduced in recent years. This therapeutic standstill is primarily due to preclinical approaches that do not fully respect the complexity of GB cell biology and fail to test efficiently anti-cancer treatments. Therefore, better treatment screening approaches are needed. In this study, we have developed a novel functional precision medicine approach to test the response to anticancer treatments in organoids derived from the resected tumors of glioblastoma patients