A Study of Different Modeling Choices For Simulating Platelets Within the Immersed Boundary Method

The Immersed Boundary (IB) method is a widely-used numerical methodology for the simulation of fluid-structure interaction problems. The IB method utilizes an Eulerian discretization for the fluid equations of motion while maintaining a Lagrangian representation of structural objects. Operators are defined for transmitting information (forces and velocities) between these two representations. Most IB simulations represent their structures with piecewise-linear approximations and utilize Hookean spring models to approximate structural forces. Our specific motivation is the modeling of platelets in hemodynamic flows. In this paper, we study two alternative representations - radial basis functions (RBFs) and Fourier-based (trigonometric polynomials and spherical harmonics) representations - for the modeling of platelets in two and three dimensions within the IB framework, and compare our results with the traditional piecewise-linear approximation methodology. For different representative shapes, we examine the geometric modeling errors (position and normal vectors), force computation errors, and computational cost and provide an engineering trade-off strategy for when and why one might select to employ these different representations.Comment: 33 pages, 17 figures, Accepted (in press) by APNU

Calcium-rich gap transients in the remote outskirts of galaxies

From the first two seasons of the Palomar Transient Factory, we identify three peculiar transients (PTF09dav, PTF10iuv, PTF11bij) with five distinguishing characteristics: peak luminosity in the gap between novae and supernovae (M_R ≈ - 15.5 to -16.5), rapid photometric evolution (t_(rise) ≈12-15 days), large photospheric velocities (≈6000 to 11000 km s^(-1)), early spectroscopic evolution into nebular phase (≈1 to 3 months) and peculiar nebular spectra dominated by Calcium. We also culled the extensive decade-long Lick Observatory Supernova Search database and identified an additional member of this group, SN 2007ke. Our choice of photometric and spectroscopic properties was motivated by SN 2005E (Perets et al. 2010). To our surprise, as in the case of SN 2005E, all four members of this group are also clearly offset from the bulk of their host galaxy. Given the well-sampled early and late-time light curves, we derive ejecta masses in the range of 0.4--0.7 M_⊙. Spectroscopically, we find that there may be a diversity in the photospheric phase, but the commonality is in the unusual nebular spectra. Our extensive follow-up observations rule out standard thermonuclear and standard core-collapse explosions for this class of "Calcium-rich gap" transients. If the progenitor is a white dwarf, we are likely seeing a detonation of the white dwarf core and perhaps, even shock-front interaction with a previously ejected nova shell. In the less likely scenario of a massive star progenitor, a very non-standard channel specific to a low-metallicity environment needs to be invoked (e.g., ejecta fallback leading to black hole formation). Detection (or lack thereof) of a faint underlying host (dwarf galaxy, cluster) will provide a crucial and decisive diagnostic to choose between these alternatives

Immunohistochemical Evaluation of P53 and P63 in Oral Squamous Cell Carcinoma, Oral Leukoplakia, Oral Submucous Fibrosis and Normal Oral Mucosa

INTRODUCTION: Oral cancer constitutes the sixth most common cancer worldwide and third most common cancer in South-East Asia. Oral squamous cell carcinoma (OSCC), the most common type of oral cancer is often preceded by potentially malignant lesions or conditions such as leukoplakia and oral submucous fibrosis (OSF). On biopsy, most leukoplakias show histologic features of epithelial dysplasia. The standardization of histopathological diagnosis and grading of epithelial dysplasia remains subjective as there are many composite histologic criteria of cellular atypia and architectural disturbances. OSF is a well recognized potentially malignant condition that is characterized by rigidity of oral mucosa and development of palpable fibrous bands, resulting from the deposition of collagen in juxtaepithelial and submucosal layers. The malignant transformation rate for leukoplakia ranges from 15-20%, while transformation rates as high as 7.6% over a 10-year period have been reported for OSF. It has been generally considered that oral carcinogenesis develops through a multistep process of accumulation of genetic mutations related to cell proliferation and differentiation. The principal targets of genetic damage include growth-promoting protooncogenes, growth-inhibiting tumor suppressor genes and genes that regulate apoptosis. Mutations in the tumor suppressor p53 gene and resultant alteration in the protein are the most common abnormalities found in squamous cell carcinoma of the head and neck region. The p53 gene encodes a 53 kD nuclear phosphoprotein that is involved in DNA repair, programmed cell death and negative regulation of cell cycle. In normal cells, wild type p53 protein has a very short half life (6-20 minutes) and is present in such small quantities that it cannot be detected by immunohistochemical methods. However, mutations in p53 gene often result in a more stable product and prolong the half life of p53 protein, causing it to accumulate within cell nuclei to the extent that it can be easily detected by immunohistochemistry. The p63 gene mapped on chromosome 3q27-29 is a member of p53 gene family and is responsible for the transcription two groups of p63 protein (TAp63 and ΔNp63), both of which have α, β and γ isoforms. The TAp63 group contains an Nterminal transactivation domain and has functions similar to p53 such as, cell cycle arrest, apoptosis and cell differentiation. The ΔNp63 group lacks TA (Transactivation) domain and acts by inhibiting both p53 and TA p63 and thus favors cell proliferation. It is suggested that p63, possibly in concert with p53 may play a role in the regulation of proliferation and differentiation in potentially malignant disorders and malignant lesions of the oral cavity. This study is done to evaluate the expression of p53 and p63 proteins in OSCC, oral leukoplakia and OSF by immunohistochemistry. AIMS AND OBJECTIVES: l. To evaluate the expression of p53 and p63 proteins in formalin fixed, paraffin embedded sections of OSCC, oral leukoplakia and OSF specimens by immunohistochemistry. 2. To compare the expression of p53 and p63 proteins in formalin fixed, paraffin embedded sections of OSCC, oral leukoplakia and OSF with normal oral mucosa by immunohistochemical methods. MATERIAL AND METHODS: Study setting: The study was conducted in the Department of Oral and Maxillofacial Pathology, Ragas Dental College and Hospital, Chennai. Study Subjects: 20 consecutive cases of oral squamous cell carcinoma (Group I), 20 consecutive cases of clinically diagnosed oral leukoplakia (Group II), 20 consecutive cases of OSF (Group III), and 10 cases of normal patients (Group IV), were collected over a period of 6 months. A preformatted clinical case sheet was used to record all the cases. Detailed case history including age, sex, and occupation, past medical and dental history along with the history of habits were recorded. This was followed by general examination and intra oral examination. Selection criteria: Group I: Clinically and histopathologically confirmed cases of OSCC. Group II: Clinically appearing white, non-scrapable patch associated with the history of tobacco habit, which was clinically diagnosed as leukoplakia and histopathologically graded as epithelial dysplasia (mild, moderate or severe). Group III: The criteria for selection of OSF patients were difficulty in opening the mouth, burning sensation of the mouth, palpable vertical fibrous bands in the oral mucosa and history of areca nut chewing. Group IV: Ten patients who reported to the outpatient department of Oral and Maxillofacial Surgery for removal of impacted third molar constituted the normal control group. Incisional biopsy of sufficient width and depth to ensure inclusion of connective tissue was taken from the buccal mucosa of the 60 study patients. Normal non-inflammed buccal mucosa adjacent to the site of surgery was biopsied for the control group. Informed consent was obtained from all the patients. The tissues taken were immediately transferred to 10% buffered formalin for further processing. After adequate fixation, paraffin blocks of the tissues were made. SUMMARY: 1. A total of 70 patients were included in the study, comprising of 20 cases of OSCC (group I), 20 cases of leukoplakia (group II), 20 cases of OSF (Group III) and 10 patients with normal oral mucosa (group IV), showing mean ages of 55.2, 43.6, 36.4 and 29.5 years respectively. 2. In group I, 80% were males and 20% were females. In group II, 100% were males. In group III, 95% were males and 5% were females. In group IV, 40% were males and 60% were females. 3. The p53 mean LI for group I, II, III and IV were 56.9 ± 21.3, 37.6 ± 12.6, 34.6 ± 8.7 and 15.1 ± 9 respectively; the difference in mean LI among the groups was statistically significant (p=0.00). The p63 mean LI for group I, II, III and IV were 56.8 ± 19.6, 42.3 ± 10.5, 32.8 ± 12.1 and 26.4 ± 9.4 respectively and the difference was statistically significant (p=0.00). 4. In group II, p53 staining was seen in the basal layer in 20% and both basal and supra basal layers in 80% of the cases. In group III, 40% exhibited basal staining, while 60% had both basal and supra basal p53 staining. In group IV, 20% of the samples had basal p53 staining and 10% had both basal and supra basal staining. The tissue localization of p53 staining was significantly different among the 3 study groups (p=0.00). 5. In group II, 10% of the cases exhibited p63 staining in the basal layer, while 90% had both basal and supra basal staining. In group III, 30% had basal stain and 70% showed basal and supra basal staining. In group IV, basal staining was seen in 50% of the samples while both basal and supra basal staining was observed in the remaining 50% of the samples. The tissue localization of p63 staining was not statistically significant among the 3 study groups (p=0.05). 6. p53 and p63 staining showed a significant positive correlation in group I and III (p=0.00; p=0.00). CONCLUSION: In conclusion, the results of the current study show that there is significantly higher expression of p53 and p63 proteins in OSCC, oral leukoplakia and OSF samples when compared to normal oral mucosa. Overexpression of p63 protein in OSCC, leukoplakia and OSF samples might be due to 1. Compensatory up-regulation of p63, resulting from mutation of p53 gene. 2. Transcriptional dysregulation of p63 gene. However, the 4A4 antibody against p63 protein, which was used in our study does not discriminate TA or ΔN type of p63, both of which has opposite functions. Further mRNA studies by RT-PCR using isoform-specific primers, will ascertain the exact role of p63 in oral carcinogenesis and also its relationship to p53 protein

Podoplanin expression in oral potentially malignant disorders and oral squamous cell carcinoma

Podoplanin is a type I transmembrane sialomucin-like glycoprotein that is specifically expressed in lymphatic endothelial cells. Studies have shown that assessment of podoplanin expression in the epithelial cells can be used to predict the malignant transformation of potentially malignant disorders and the metastatic tendency of primary head and neck squamous cell carcinoma. The aim of our study was to compare the expression of podoplanin in oral leukoplakia, oral submucous fibrosis and oral squamous cell carcinoma with that in normal buccal mucosa by immunohistochemical methods. Immunohistochemical expression of podoplanin was analyzed in 20 cases each of oral leukoplakia, oral submucous fibrosis, oral squamous cell carcinoma and normal buccal mucosa, with monoclonal antibody D2-40. The expression of podoplanin was graded from grade 0-4. There was a statistically significant upregulation of the grades of podoplanin expression in oral squamous cell carcinoma(100%), oral submucous fibrosis (90%) and oral leukoplakia (65%) when compared to that in normal mucosa(35%). Podoplanin expression increased with decrease in grades of differentiation in oral squamous cell carcinoma . Podoplanin expression in the samples of oral submucous fibrosis was higher than that in oral leukoplakia. Evaluation of podoplanin expression in the epithelial cells of oral dysplastic lesions may provide valuable information to predict their risk of malignant transformation

Evidence for Filamentarity in the Las Campanas Redshift Survey

We apply Shapefinders, statistical measures of `shape' constructed from two dimensional partial Minkowski functionals, to study the degree of filamentarity in the Las Campanas Redshift Survey (LCRS). In two dimensions, three Minkowski functionals characterise the morphology of an object, they are: its perimeter (L), area (S), and genus. Out of L and S a single dimensionless Shapefinder Statistic, F can be constructed (0 <=F <=1). F acquires extreme values on a circle (F = 0) and a filament (F = 1). Using F, we quantify the extent of filamentarity in the LCRS by comparing our results with a Poisson distribution with similar geometrical properties and having the same selection function as the survey. Our results unambiguously demonstrate that the LCRS displays a high degree of filamentarity both in the Northern and Southern galactic sections a result that is in general agreement with the visual appearance of the catalogue. It is well known that gravitational clustering from Gaussian initial conditions gives rise to the development of non-Gaussianity reflected in the formation of a network-like filamentary structure on supercluster scales. Consequently the fact that the smoothed LCRS catalogue shows properties consistent with those of a Gaussian random field (Colley 1997) whereas the unsmoothed catalogue demonstrates the presence of filamentarity lends strong support to the conjecture that the large scale clustering of galaxies is driven by gravitational instability.Comment: Accepted for publication in Ap

A dynamic method for charging-up calculations: the case of GEM

The simulation of Micro Pattern Gaseous Detectors (MPGDs) signal response is an important and powerful tool for the design and optimization of such detectors. However, several attempts to simulate exactly the effective charge gain have not been completely successful. Namely, the gain stability over time has not been fully understood. Charging-up of the insulator surfaces have been pointed as one of the responsible for the difference between experimental and Monte Carlo results. This work describes two iterative methods to simulate the charging-up in one MPGD device, the Gas Electron Multiplier (GEM). The first method uses a constant step for avalanches time evolution, very detailed, but slower to compute. The second method uses a dynamic step that improves the computing time. Good agreement between both methods was reached. Despite of comparison with experimental results shows that charging-up plays an important role in detectors operation, should not be the only responsible for the difference between simulated and measured effective gain, but explains the time evolution in the effective gain.Comment: Minor changes in grammatical statements and inclusion of some important information about experimental setup at section "Comparison with experimental results

Tracing the Orphan Stream to 55 kpc with RR Lyrae Stars

We report positions, velocities and metallicities of 50 ab-type RR Lyrae (RRab) stars observed in the vicinity of the Orphan stellar stream. Using about 30 RRab stars classified as being likely members of the Orphan stream, we study the metallicity and the spatial extent of the stream. We find that RRab stars in the Orphan stream have a wide range of metallicities, from -1.5 dex to -2.7 dex. The average metallicity of the stream is -2.1 dex, identical to the value obtained by Newberg et al. (2010) using blue horizontal branch stars. We find that the most distant parts of the stream (40-50 kpc from the Sun) are about 0.3 dex more metal-poor than the closer parts (within ~30 kpc), suggesting a possible metallicity gradient along the stream's length. We have extended the previous studies and have mapped the stream up to 55 kpc from the Sun. Even after a careful search, we did not identify any more distant RRab stars that could plausibly be members of the Orphan stream. If confirmed with other tracers, this result would indicate a detection of the end of the leading arm of the stream. We have compared the distances of Orphan stream RRab stars with the best-fit orbits obtained by Newberg et al. (2010). We find that model 6 of Newberg et al. (2010) cannot explain the distances of the most remote Orphan stream RRab stars, and conclude that the best fit to distances of Orphan stream RRab stars and to the local circular velocity is provided by potentials where the total mass of the Galaxy within 60 kpc is M_{60}~2.7x10^{11} Msun, or about 60% of the mass found by previous studies. More extensive modelling that would consider non-spherical potentials and the possibility of misalignment between the stream and the orbit, is highly encouraged.Comment: Submitted to ApJ, 15 pages in emulateapj format, three tables in machine-readable format (download "Source" from "Other formats"