Gotowa bibliografia na temat „MPPED2”

Background: We have recently reported the downregulation of the Metallophosphoesterase-domain-containing protein 2 (MPPED2) gene and its cognate long non-coding RNA, MPPED2-AS1, in papillary thyroid carcinomas. Functional studies supported a tumor suppressor role of both these genes in thyroid carcinogenesis. We then decided to investigate their role in breast carcinogenesis. Methods: In order to verify MPPED2 expression, 45 human breast carcinoma samples have been investigated by quantitative real-time polymerase chain reaction (qRT-PCR). Then, MPPED2 has been transfected in several human breast carcinoma cell lines, analyzing its role in cell proliferation, migration and invasion. To study the regulation of MPPED2 expression the methylation of its promoter was investigated by targeted bisulfite sequencing. Results: MPPED2 expression was decreased in breast cancer samples, and this was confirmed by the analysis of data available in The Cancer Genome Atlas (TCGA). Interestingly, the hypermethylation of MPPED2 promoter likely accounted for its downregulation in breast cancer. Additionally, MPPED2-AS1 was also found downregulated in breast cancer tissues and, intriguingly, its expression decreased the hypermethylation of the MPPED2 promoter by inhibiting DNA methyltransferase 1 (DNMT1). Furthermore, the restoration of MPPED2 expression reduced cell proliferation, migration and invasion capability of breast carcinoma cell lines. Conclusion: Taken together, these results propose MPPED2 downregulation as a critical event in breast carcinogenesis.

Abstract Objectives Improved molecular testing for common somatic mutations and identification of mRNA and microRNA expression classifiers have emerged as the most promising approaches for diagnosis of thyroid nodules. However, it is necessary to effectively increase diagnostic accuracy further. Currently, lncRNA research has moved to the forefront of human cancer research, as recent findings have revealed a crucial role of lncRNAs in gene modulation. We evaluated the diagnostic value of the selected lncRNAs from The Atlas of Noncoding RNAs in Cancer (TANRIC) thyroid cancer dataset. Methods Using TANRIC thyroid cancer dataset, we compared 12,727 lncRNAs from the thyroid cancer tissues of 59 thyroid cancer patients with paired normal thyroid tissues. lncRNAs with significantly increased or decreased expression in thyroid cancer tissues were selected as candidates for thyroid cancer diagnosis. The expression levels of candidate lncRNAs were confirmed in patients with thyroid nodules who underwent surgery at the Severance Hospital. Subsequently, the candidate lncRNAs were applied to actual fine needle aspiration to verify their diagnostic value. Results LRRC52-AS1, LINC02471, LINC02082, UNC5B-AS1, LINC02408, MPPED2-AS1, LNCNEF, LOC642484, ATP6V0E2-AS1, and LOC100129129 were selected as candidates for thyroid cancer diagnosis. The expression levels of LRRC52-AS1, LINC02082, UNC5B-AS1, MPPED2-AS1, LNCNEF, and LOC100129129 were significantly increased or decreased in malignant nodules compared to their expression levels in benign nodules or paired normal thyroid tissues in our surgical tissue samples. The combination of LRRC52-AS1, LINC02082, and UNC5B-AS1 showed favorable results, with 89% sensitivity and 100% specificity, for thyroid cancer diagnosis using fine needle aspiration. Conclusions lncRNA expression analysis could be a promising approach for advancing molecular diagnosis of thyroid cancer. Further studies are needed to discover lncRNAs of additional diagnostic value. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

AbstractMigraine affects over a billion individuals worldwide but its genetic underpinning remains largely unknown. Here, we performed a genome-wide association study of 102,084 migraine cases and 771,257 controls and identified 123 loci, of which 86 are previously unknown. These loci provide an opportunity to evaluate shared and distinct genetic components in the two main migraine subtypes: migraine with aura and migraine without aura. Stratification of the risk loci using 29,679 cases with subtype information indicated three risk variants that seem specific for migraine with aura (in HMOX2, CACNA1A and MPPED2), two that seem specific for migraine without aura (near SPINK2 and near FECH) and nine that increase susceptibility for migraine regardless of subtype. The new risk loci include genes encoding recent migraine-specific drug targets, namely calcitonin gene-related peptide (CALCA/CALCB) and serotonin 1F receptor (HTR1F). Overall, genomic annotations among migraine-associated variants were enriched in both vascular and central nervous system tissue/cell types, supporting unequivocally that neurovascular mechanisms underlie migraine pathophysiology.

Dental caries is the most common chronic disease in children and a major public health concern due to its increasing incidence, serious health and social co-morbidities, and socio-demographic disparities in disease burden. We performed the first genome-wide association scan for dental caries to identify associated genetic loci and nominate candidate genes affecting tooth decay in 1305 US children ages 3-12 yrs. Affection status was defined as 1 or more primary teeth with evidence of decay based on intra-oral examination. No associations met strict criteria for genome-wide significance (p < 10E-7); however, several loci ( ACTN2, MTR, and EDARADD, MPPED2, and LPO) with plausible biological roles in dental caries exhibited suggestive evidence for association. Analyses stratified by home fluoride level yielded additional suggestive loci, including TFIP11 in the low-fluoride group, and EPHA7 and ZMPSTE24 in the sufficient-fluoride group. Suggestive loci were tested but not significantly replicated in an independent sample (N = 1695, ages 2-7 yrs) after adjustment for multiple comparisons. This study reinforces the complexity of dental caries, suggesting that numerous loci, mostly having small effects, are involved in cariogenesis. Verification/replication of suggestive loci may highlight biological mechanisms and/or pathways leading to a fuller understanding of the genetic risks for dental caries.

Abstract The genomic organization and mRNA expression of the human GNAL gene on chromosome 18p11.2, a region that has been associated with bipolar disorder and schizophrenia, was determined. The GNAL gene was shown to span over 80 kb and consist of twelve exons, and its structure was very similar to adenyl cyclase stimulating G protein GSα. The start site of transcription was revealed by 5'-RACE. Two polyadenylation signals were found, and 3'-RACE assay was used to verify the functional site. The GNAL gene was expressed as approximately 6 kb transcripts in various regions of the human brain, and no alternative splicing was detected. One informative CA-dinucleotide repeat of 11 alleles and 74% heterozygosity was found in intron 5, and two single nucleotide polymorphisms in introns 3 and 10 were detected by SSCP. During characterization of the GNAL gene, two previously unknown genes were found. A novel intronless gene C18orf2 coding for a functionally unknown protein was localized to intron 5 of the GNAL gene. By semiquatitative RT-PCR, C18orf2 mRNA was found to be moderately expressed in all tissues studied here. Another novel gene, metallophosphoesterase MPPE1, was found to reside adjacent to the 3'-end of the GNAL gene in a tail-to-tail orientation. The deduced amino acid sequence revealed a highly conserved metallophosphoesterase motif gDxH..(16-60)..GDxxdr..(13-34)..GNH[DE], which is typical for various phosphate hydrolyzing enzymes, especially serine/threonine protein phosphatases. The MPPE1 gene contained fourteen exons and spanned about 27 kb. MPPE1 was expressed as a single mRNA of 2.2 kb in various regions of the human brain but not in any other tissues. Four different alternatively spliced forms of MPPE1 were detected by RT-PCR, and each transcript was shown to partially overlap with the 3'-untranslated region of the GNAL gene.

A large number of evolutionarily conserved genes have been identified by comparative genomics approaches. However, a considerable fraction of these genes lack functional characterization despite the availability of several bioinformatics approaches for prediction of protein function. Moreover, with the advent of genome sequencing efforts, numerous disease associated genes have been identified. While high throughput approaches aid in identification of genes, studying individual genes is important to understand their cellular roles. During studies on cyclic AMP metabolism in mycobacteria conducted in the laboratory, a Class III cyclic nucleotide phosphodiesterase, Rv0805 was identified from Mycobacterium tuberculosis. Interestingly, additional bioinformatics analysis identified orthologs were in higher eukaryotes. These were members of the metallophosphoesterase-domain-containing protein 1 (MPPED1) and metallophosphoesterase-domain-containing protein 2 (MPPED2) family. Class III cyclic nucleotide phosphodiesterases were previously reported only in prokaryotes and are distinct from Class I cyclic nucleotide phosphodiesterases generally found in eukaryotes. Thus MPPED1 and MPPED2 proteins were the first identified eukaryotic Class III cyclic nucleotide phosphodiesterases. In humans, MPPED2 is located on chromosome 11 in the region p13-14 that has been associated with WAGR (Wilms’ tumor, aniridia, genitourinary anomalies, and mental retardation) syndrome. Inspection of this region across sequenced mammalian genomes has revealed a shared synteny. Most interestingly, a stretch of 200 bp within the coding sequence of MPPED2 is identified to be one of 481 ultra conserved regions within the human genome. Furthermore, orthologs of MPPED2 can be traced all the way back to Drosophila melanogaster and Caenorhabditis elegans. All of these observations indicate that MPPED2 is highly conserved and hints at its likely importance in many organisms. MPPED1 and MPPED2 have been reported to be expressed in adult and fetal brain respectively and have been annotated as metallophosphoesterases. Metallophosphoesterases are a superfamily of proteins that show wide phyletic distribution and exhibit diversity in their substrate utilization and function. Previous studies from the laboratory have shown that MPPED1 and MPPED2 are indeed metallophosphoesterases and demonstrate cyclic nucleotide phosphodiesterase activity. The crystal structure of MPPED2 was obtained in collaboration with Dr. Marjetka Podobnik (National Institute of Chemistry, Slovenia). Interestingly, the crystal structure of MPPED2 revealed the presence of bound 5’GMP molecule at the active site, and this finding was investigated further in this thesis. MPPED2 bound 5’GMP and 5’AMP with high affinity (IC50 of ~70 nM) which inhibited the activity of MPPED2. Key residues involved in stabilising the 5’ nucleotide have been identified by structure guided mutational analysis. The MPPED2-G252H mutant, generated to mimic the active site of MPPED1, also bound 5’GMP or 5’AMP but with much lower affinity. Given the high affinity of MPPED2 towards 5’GMP/5’AMP, it can be speculated that MPPED2 may show poor phosphodiesterase activity in the cell, and could function in a catalytically-independent manner, perhaps as a scaffolding protein. MPPED1 on the other hand may have a catalytic role that could be regulated by intracellular levels of 5’AMP, 5’GMP and their respective cyclic nucleotides. In order to investigate the biological role of the MPPED1/MPPED2 family of proteins, Drosophila melanogaster was chosen as a model organism owing to the presence of a single ortholog, CG16717, in its genome. Biochemical characterization of CG16717 revealed that the protein was in fact a metallophosphodiesterase capable of hydrolysing cyclic AMP and cyclic GMP, albeit poorly. CG16717 could be inhibited by 5’ nucleotides at high concentrations that may seldom be achieved in-vivo, suggesting that CG16717 may have roles in the organism that depend on its catalytic activity. CG16717 has not been functionally characterized previously. In this thesis, a detailed analysis of CG16717 expression pattern has been performed. CG16717 was found to be expressed in all stages of the fly lifecycle. In adult female flies, levels of CG16717 increased across age. Moreover, CG16717 was not differentially regulated under conditions of starvation, paraquat-induced oxidative stress or in the presence of heavy metals. Spatial expression analysis revealed that CG16717 was expressed in all adult tissues tested, with maximal expression in the brain, suggesting that neuronal expression of CG16717 may be important for its function. Attempts to identify specific cells expressing CG16717 using an enhancer-promoter analysis were not successful. In order to elucidate the physiological role of CG16717, and after having ruled out options of using a P-element insertion mutant and RNA interference approaches, a targeted knock-out of CG16717 was generated using homologous recombination based genomic engineering. CG16717KO flies generated were homozygous viable suggesting that CG16717 was dispensable for fly survival at least under normal laboratory conditions. In line with high expression of CG16717 in the brain and in-vitro ability of CG16717 to hydrolyse cAMP and cGMP, CG16717KO flies showed two to three-fold higher levels of cyclic nucleotides in the head fraction than wild-type flies. C25E10.12, one of the three C. elegans orthologs of CG16717 has been identified to be a target of the transcription factor daf-16 (FOXO) that is inhibited by active insulin signalling. Moreover, knock-down of C25E10.12 reduced the lifespan of age-1 (PI3K) mutant worms. In contrast to this, CG16717 was not found to be differentially regulated in dFOXO null flies. CG16717KO flies however, showed median lifespan that was shorter than control wild-type flies even in the presence of functional PI3K. Various genetic approaches were employed to verify if reduced lifespan was indeed a consequence of loss of CG16717. In the first approach, a wild-type copy of CG16717 was re-introduced at the genomic locus of CG16717 in the CG16717KO flies using attP-attB recombination. However, this approach could not rescue the reduced lifespan of CG16717KO flies, probably due to very low expression of CG16717. In the second approach, CG16717 was reconstituted using genomic constructs containing a copy of CG16717. Finally, CG16717 was expressed ubiquitously using the bipartite Gal4/UAS system. Both the genomic construct and the expression of CG16717 using the Gal4/UAS approach were able to restore the lifespan of CG16717KO flies. More importantly, overexpression of CG16717 in an otherwise wild-type fly led to enhanced lifespan over and above that of control flies. All of these together suggested that CG16717 plays a critical role in regulating lifespan. Mutants of the insulin and target of rapamycin (TOR) signalling pathways have previously been reported to show lifespan extension. Moreover, these mutants have also been associated with reduced growth, increased stress resistance and reduced fecundity. Given the reduction in lifespan of CG16717KO flies, the other insulin/TOR signalling associated phenotypes were tested. While CG16717KO flies showed no difference in terms of developmental growth, and resistance to starvation or paraquat induced oxidative stress, CG16717KO flies were less fecund compared to wild-type controls. Multiple approaches were adopted even in the case of reduced fecundity to verify if the observed phenotype was a consequence of loss of CG16717. However, neither reconstitution of CG16717 using the genomic construct nor ubiquitous expression of CG16717 using the bipartite Gal4/UAS system were able to rescue the reduced fecundity phenotype of CG16717KO flies. This suggested that reduced fecundity in CG16717KO flies was probably not linked to CG16717 and was a consequence of a second mutation at a site distinct from CG16717. Two other approaches were employed to confirm these observations. When CG16717KO/Deficiency lines were tested, these showed fecundity comparable to wild-type control flies despite the lack of CG16717. CG16717KO flies were extensively out-crossed in an attempt to segregate the second site mutation from the CG16717 locus and their fecundity was tested. However, these flies which retained the deletion of CG16717, showed fecundity comparable to wild-type control flies, reiterating that reduced fecundity was not linked to loss of CG16717. In an attempt to find possible links between reduced longevity of CG16717KO flies and the well-established insulin/TOR pathways, transcript levels of key players of these pathways were measured by qRT-PCR. The translational repressor 4EBP was found to be upregulated in CG16717KO flies compared to wild-type control flies. Interestingly, increased 4EBP levels have been associated with enhanced lifespan but in this case despite higher levels of 4EBP, CG16717KO flies showed reduced lifespan. Phosphorylation status of 4EBP and other players involved in the insulin/TOR phosphokinase signalling cascade would shed light on the activity of these pathways. In summary, this thesis has attempted to understand the biochemistry and physiological functions of an evolutionarily conserved metallophosphoesterase. Its apparent role in regulating life span in the fly suggests that the functions of this protein are likely to impinge on a number of diverse and important pathways involved in basic physiological processes in the organism. Further investigation would shed light on the molecular basis by which CG16717 affects lifespan, and opens up new avenues to understanding the contributions of CG16717 in regulating lifespan and diverse neurological functions.

碩士
國立陽明大學
生命科學暨基因體科學研究所
98
Metallophosphoesterase domain containing gene 1 (MPPED1) is a novel gene and mainly expressed in the brain. Our lab has demonstrated mouse Mpped1 expressing from embryonic to adult stages and mainly in the neocortex and the hippocampal CA1 region, which suggest that Mpped1 may play some roles during telencephalic development. We further analyze the earliest time point of Mpped1 expression in the neocortex and examine the potential cause of reduced Mppped1 expression level in the Emx1Cre; ??cateninf/f malformed cortex observed in previous studies. We find that Mpped1 starts to express at E13.5 and that the migration defect in ??catenin-deficient cortex is the major reason to reduce the upper cortical layer cells, which in turn decreased Mpped1 expression. Based on these findings, we hypothesize that Mpped1 is expressed in the postmitotic cells arriving in the cortical layer where they are destined for. Moreover, to gain insight into the biological function of Mpped1, Mpped1 conventional knockout mice were generated. Since Mpped1 has been found to mainly express in the neocortex and interact with Coup-TFI (Chicken Ovalbumin Upstream Promoter Transcriptional Factor 1), an intrinsic factor playing a crucial role in the area patterning, we have characterized its role in the cortical lamination and arealization. The results show that loss of Mpped1 has no effect on cortical architecture, but leads to expansion of the motor area and compression of the primary visual area in the neocortex of Mpped1lacZ-neo/lacZ-neo mouse. We also characterize the expression pattern of Mpped1 on the neocortical surface of Mpped1lacZ/+ mice by X-gal staining. A region-specific expression of Mpped1 has been observed, where seems to be the primary somatosensory area. In summary, these data reveals that Mpped1 may play an important role in regulating area patterning during neocortical development.

碩士
國立陽明大學
生命科學暨基因體科學研究所
97
MPPED1, Metallophosphoesterase Doamin Containing Gene 1, encodes a novel protein with unknown function and is highly conserved from nematodes and insects to birds and mammals. Human MPPED1’s transcript has been identified in adult brain, indicating that MPPED1 may play an important role in central nervous system. To gain insight into biological functions of MPPED1, the expression of Mpped1 are systematically analyzed through mouse brain ontogeny. Mpped1 is highly expressed in the postmitotic region of the neocortex and CA1 region of the hippocampus from embryonic to adult stage, but not in the thalamus, the spinal cord and the cerebellum, suggesting that Mpped1 may participate in telencephalic development. To further investigate the function of MPPED1, several proteins have been identified to interact with MPPED1 through yeast two-hybrid screening in our lab, including COUP-TFI and ERK5. COUP-TFI (Chicken Ovalbumin Upstream Promoter Transcriptional Factor 1) is an important intrinsic factor for early regionalization of neocortex. To examine whether MPPED1 involves in the cortex arealization or not, whole mount in situ hybridization experiments are performed to identify the expression pattern of MPPED1 on the surface of neocortex. MPPED1 does not display expression gradient as like COUP-TFI exhibiting high-caudal to low-rostral expression gradient. In addtion, by performing in situ hybridization and immunofluorescence staining, MPPED1, COUP-TFI and ERK5 are found to show the same expression distribution in brain neocortex and hippocampal CA1. Finally, the expression patterns of MPPED1 are characterized in the beta-catenin and SHH mutant neocortex, and the expression level of Mpped1 is reduced in the Emx1-Cre;beta-catfx/fx malformed neocortex. In summary, these results indicate that MPPED1 may be responsible for certain functions in neocortex and hippocampus during telencephalic development.

Mercury is the closest planet to the Sun in the Solar System and because of this, its study has been a challenging task. BepiColombo/MMO is an orbiter part of a mission to Mercury with the goal of studying Mercury's magnetic field and magnetosphere. The orbiter is being developed by ISAS-JAXA. The studies are done using a five instruments payload. One of them is the Mercury Plasma Particle Experiment (MPPE) which will study low and high energy electrons/ions and energetic neutrals. The low-energy ion measurements are done using the Mercury Ion Analyzer (MIA) sensor, which is part of the MPPE.The MIA sensor requires calibration and testing to ensure its adequate operation. The testing will prove that the MIA sensor will be able to operate adequately in the Bepi-Colombo mission. This thesis work covers a series of factors that are required to verify the performance of the sensor. These factors are the degradation of the Micro-Channel Plate over time, the survival to vibration and thermal vacuum environments and the development of the software model of the sensor. These factors were evaluated with a MCP life test, qualification testing on the form of vibration and thermal vacuum tests and comparison of the sensor model response to the expected plasma environment around Mercury.The results of the MCP life test show that the MCP degrades faster at high temperatures, however, it will be able to survive the two year mission to Mercury. The qualification testing showed that the MIA sensor is able to withstand the vibration conditions in the mission. However, it will be until a new thermal vacuum test is done that it will be considered that the MIA sensor can withstand the expected thermal conditions. Finally, the response of the software model of the MIA sensor is in accordance to the expected plasma environment around Mercury. Therefore, it could be used to test the accuracy of the velocity moments calculation of the MDP1 software. Overall, the calibration and testing of the MIA sensor still continues. However, the results so far show that it will probe that it can operate under the conditions that the BepiColombo mission requires.

Validerat; 20121116 (global_studentproject_submitter)

By February of 1939, Motion Picture Pictures and Distributors Association (MPPDA) President Will Hays argued that movies needed more realism connecting to the types of problems that face average Americans. With growing anti-Nazi sentiment in Hollywood, the release of Confessions of a Nazi Spy on May 6^th would become a watershed moment for an industry largely cautious of how they should approach the growing unrest in Europe. At the same time, Hitler’s Minister of Propaganda, Joseph Goebbels, discontinued the shipment of official Nazi war films to the United States. Producer Walter Wanger and radio journalist Jimmie Fidler took to blows in the press. Wanger claimed the Hollywood press was a joke while Fidler defending his work. In February 1940, MPPDA president Will Hays sent out a report commending the cultural importance of movies during the 1930s as “exposing the tragedy of war.”

Chapter Five pays special attention to writer-director-actor Larry Semon, who transformed the company's approach to comedy from reality-based characters and situations to absurd, frenetic slapstick. This resulted in Semon emerging as Vitagraph's biggest box office star of the 1920s. The popularity of Western-themed serials is covered, as is the rise of Corinne Griffith in becoming Vitagraph's leading female star. Two of the company's most critical and popular successes, Black Beauty and Captain Blood, are considered in depth. Albert Smith's battles with Adolph Zukor, whose initial efforts to "smash Vitagraph" are covered in the previous chapter, culminate here with Vitagraph's decision to bring suit against Paramount for violation of the Clayton Anti-Trust Act, which is analyzed in detail. Related is Vitagraph's withdrawal from the MPPDA and its criticism of president Will Hays as a shill for Paramount. The chapter concludes with Smith's decision to sell Vitagraph to Warner Bros. in 1925.

MPPDA president Will Hays observed that only a small number of films dealt with the conflict in Europe. While critics of Hollywood would soon refer to film primarily as a means of amusement, Hays defined films as “a medium of information, education, and entertainment.” Anti-Hollywood sentiment was amplified in a pamphlet written by G. Allison Phelps. An American’s History of Hollywood opens with the claim that Hollywood is largely informed by its many Russian immigrant employees, and, therefore, is an industry led by communists. Phelps’ evidence, without listing specific productions, was that “the Hollywood leaders, in selecting ‘literature’ from which to produce pictures, reached far back into Russia to bring forth the embryo of atheism, the oriental germ of eroticism, [and] the seeds of lust and hatred.” The summer of 1941 saw two competing events in Los Angeles that would serve as a primer for coming debates. Two rallies were held at the Hollywood Bowl, one isolationist rally featuring Charles Lindbergh and an interventionist rally featuring Wendell Willkie.

Curtiz’s career is summarized during the pre-Code era of Hollywood films. The evolution of the Production Code from the 1922 appointment of Will Hays as the czar of the MPPDA to the lack of enforcement of the Code is contextually chronicled as a key driver of the nature of Warner Bros. pictures during the early years of the Depression. Zanuck pioneered the “ripped from the headlines” gangster dramas that struck a chord with audiences. After he directed The Mad Genius, with John Barrymore, Curtiz’s pay was cut as Warners lost $8 million in 1931.Following The Woman from Monte Carlo and the visually creative Alias the Doctor, Curtiz was assigned the contemporary Strange Love of Molly Louvain, starring Ann Dvorak.He hit box-office gold with Doctor X (1932), a gruesome pre-Code horror film starring Fay Wray, who recounted Curtiz’s cold, sometimes cruel behavior on the set. Curtiz’s production of The Cabin in the Cotton included his racial faux pas and his alienation of Bette Davis during their first film together.His masterly direction of 20,000 Years in Sing Sing concluded a year of worsening economic conditions for the country.

Abstract. Introduction. Ambient air pollution with particulate matter from various sources sig-nificantly increases the risk of human health disorders. The concentrations of the total suspended particles (TSP), as well as the PM2.5 and PM10 fractions, are mainly monitored. In fact, the ac-tual size distribution of aerosol particles differs significantly from the stepwise distribution formed only by the concentrations of PM2.5 and PM10. Aim of the study: development of a method for reconstructing the size distribution function of aerosol particles from the actual concentrations of PM2.5 and PM10 under the assumption of a lognormal size distribution for calculation of doses deposited in different lung regions. Methods. Long-term concentrations of various fractions of particles in the ambient air were ob-tained from the database of social and hygienic monitoring created by the "Center for Hygiene and Epidemiology in the Republic of Tatarstan (Tatarstan)". A reconstructed theoretical particle size distribution function f0(dp) was derived using the numerical solution, and the corresponding software was developed. The MPPD (Multiple-Path Particle Dosimetry) software was used to calculate the particle deposited doses in different areas of the human respiratory tract. Results. The measured values of the PM2.5 and PM10 concentrations were used to derive the lognormal aerosol size distribution. Based on the calculation of the mass doses of settled particles in the human respiratory system using MPPD (Multiple-Path Particle Dosimetry) code, it is shown that the calculation based only on the values of PM2.5 and PM10 leads to an underestimation of the mass fractions of particles in the lower respiratory tract and alveolar zone, the values of which are determinant for the estimation of the risk of lung disease. Conclusions. The proposed method for reconstructing the size distribution function of the con-centration of aerosol particles is important for a quantitatively reliable assessment of the risks of exposure to ambient air aerosols, making it possible to move from assessment of external expo-sures to the calculation of deposited fractions. The use of deposited fractions as an exposure pa-rameter increases the accuracy of health risk assessments associated with particulate matter ex-posure. This approach can be used both in the study of ambient aerosols and for the air of the working area.

Unstable optical resonators that use a super-Gaussian reflectivity output coupler have been demonstrated to be successful in generating coherent radiation from high gain and large transverse-mode volume lasers. In the past, the design procedure for these resonators has been based on the geometrical-optics solution for the transverse eigenmodes, in which the fundamental mode is also a super-Gaussian of the same order as the mirror. In this work, the limits of validity of the geometrical-optics solution are quantified by numerically solving for the diffractive (Fox-Li) transverse eigenmodes as a function of the Gaussian-aperture-equivalent Fresnel number Neq. It is shown that for low cavity magnifications (M ≤ 2), the diffractive eigenvalues deviate from the geometrical-optics value for Neq ≤ 2. At these low equivalent Fresnel numbers, the transverse mode structure is determined by propagation effects (diffractive spreading), in addition to the mirror reflectivity profile. Furthermore, resonators with super-Gaussian mirrors of order n ≥ 6 exhibit transverse mode crossing points when Neq ≤ 2. Near a mode crossing point, the fundamental mode resembles a higher-order ring mode with a large central depression. The implications for the design of these resonators will be discussed.

The usual description of imaging in a microscope is based on scalar diffraction theory and on some approximations to model the interaction of the electromagnetic field and the object. The validity of this description becomes suspect when there is structure in the object comparable to the wavelength of light and when the object is optically thick (< λ/4). Unfortunately, these cases are of interest in many practical applications, such as the inspection and metrology of integrated circuits.

The FDTD method solves the complete vector Maxwell’s equations for a photonics device, and can be used to simulate devices of one, two or three-dimensional complexity. We show the use of this method with a number of 2-D integrated photonics devices including gratings, diodes, and complex guiding structures. These simulations will include both TE and TM polarizations as well as an infinite number of guided and free-space modes. The time-domain nature of the algorithm is exploited to produce the complete frequency-response of the devices under simulation. These FDTD results are compared with experiment, theory, and other simulations methods (such as the beam propagation method) to demonstrate their validity.