Specific Morphological Parameters Research Articles

Complement system component 3 deficiency modulates the phenotypic profile of murine macrophages

The Complement System is composed of more than 40 proteins that act in innate and adaptive immunity. C3 is the most abundant one and C3-deficient patients are more susceptible to recurrent and severe infections. Several studies have demonstrated the importance of C3 in controlling infections. However, its role in leukocyte biology is still poorly understood. This study aimed to evaluate several cellular parameters in macrophages from C3-deficient mice and compare them to similar cells from wild-type counterparts. We observed that in the absence of C3, the population of F4/80low macrophages in the peritoneal cavity of thioglycolate-treated mice is diminished, probably due to the lack of chemotactic factors like C3a and low levels of C5a. Using fluorescence microscopy analysis, we observed that macrophages from C3-deficient mice exhibited morphological alterations when compared to similar cells from wild-type mice. We observed a significant increase in the expression of CD11c, which is part of CR4 (CD11c/CD18), in macrophages from C3-deficient compared to cells from wild-type mice. Treatment with 12-o-tetradecanoylphorbol-13-acetate, stimulated ROS production and MAPK activation by macrophages. However, these parameters were lower in macrophages from C3-deficient mice when compared to wild-type counterparts. In addition, the phagocytosis of iC3b-opsonized Zymosan particles was diminished in macrophages from C3-deficient mice. Our results suggest that C3 deficiency in C57Black/6 mice may influence specific morphological and functional parameters of macrophages, cells of fundamental importance for both the innate and acquired immune responses.

A Modern Multidisciplinary Method to Characterize Natural White Spot Lesions with 2D and 3D Assessments: A Preliminary Study.

In this preliminary study, a multidisciplinary method based on high-resolution analytical techniques (such as microcomputed tomography, Raman Microspectroscopy, scanning electron microscopy, and Vickers microhardness test) was exploited to evaluate the alterations that occur in human teeth at the initial stage of the carious lesion. To this purpose, six extracted molars displaying a natural white spot lesion (WSL) were investigated. Specific morphological, structural, and chemical parameters, such as the mineral density, indentation hardness, molecular and elemental composition, and surface micromorphology were obtained on the WSL, and the results were statistically compared (t-test, p < 0.05) to those of the sound enamel on the same tooth. In the WSL, with respect to the sound area, a decrease in the mineral density and crystallinity was detected together with differences in the molecular composition and surface microstructure, such as the occurrence of micropores and irregularities. Moreover, the elemental analysis highlighted in WSL showed a statistically significant decrease in Ca and P percentages. In conclusion, this multidisciplinary approach allows us to fully characterize the area of interest, providing a deeper knowledge of these enamel lesions, which could have important clinical implications.

Coastal flood susceptibility assessment along the Northern coast of Portugal

Assessing the susceptibility of sandy beaches to flooding during major storms is an important topic, given the implications that these events can have for beach-dependent coastal systems. A flood susceptibility index based on wave run-up, storm surge and beach morphology is applied to three sectors of the northwest coast of Portugal. An extended ERA5 wave dataset is used (1950–2022) to characterize the most frequent storm events, and topographic data from aerial UAV surveys are examined to obtain specific morphological parameters of the sandy beaches – mean face slope and height of the beach. The flood susceptibility index results show that 54 % of the analyzed coast is classified with extreme or very high susceptibility. The most critical sector is the coastal stretch between Cortegaça and Torrão do Lameiro beaches, where mostly natural systems are present, while the urban front of Furadouro is frequently flooded during storm events. Between Miramar beach (south) and Paramos beach, with a susceptibility index classified between medium and extreme, the presence of some urban fronts points to high-risk exposure situations. The sector between São Jacinto and Poço da Cruz beaches presented lower susceptibility levels for the three urban areas. The problem does not end with the threat to urban fronts, which already have several defense structures, but it is also extends to dune systems and sand dykes.

Relationship between trapeziometacarpal joint morphological parameters and joint contact pressure: a possible factor of osteoarthritis development

The trapeziometacarpal (TMC) joint is the one of the hand joints that is most affected by osteoarthritis (OA). The objective of this study was to determine if specific morphological parameters could be related to the amount of pressure endured by the joint which is one of the factors contributing to the development of this pathology.We developed 15 individualized 3D computer aided design (CAD) models of the TMC joint, each generated from the CT scan of a different participant. For each participant, we measured several crucial morphological parameters: the width and length of the trapezium bone and dorso-volar and ulno-radial curvature, of the trapezium and the metacarpal bone. Each CAD model was converted into a finite element model, of both bones and the cartilage located in between. The joint forces applied during pinch grip and power grip tasks were then applied in order to estimate the contact pressures on joint cartilage for each model. Correlations between joint contact pressures and morphology of the trapezium and the metacarpal bone were then analysed.Important variations of TMC joint pressures were observed. For both pinch and power grip tasks, the strongest correlation with joint contact pressure was with the dorso-volar curvature of the trapezium bone.Our findings indicate that dorso-volar curvature of the trapezium bone has a significant impact on mechanical loadings on the TMC joint. This contributes to understanding the prevalence of OA in certain patients.

Lack of reproducibility of histopathological features in MYC-rearranged large B cell lymphoma using digital whole slide images: a study from the Lunenburg lymphoma biomarker consortium.

Subclassification of large B cell lymphoma (LBCL) is challenging due to the overlap in histopathological, immunophenotypical and genetic data. In particular, the criteria to separate diffuse large B cell lymphoma (DLBCL) and high-grade B cell lymphoma (HGBL) are difficult to apply in practice. The Lunenburg Lymphoma Biomarker Consortium previously reported a cohort of over 5000 LBCL that included fluorescence in-situ hybridisation (FISH) data. This cohort contained 209 cases with MYC rearrangement that were available for a validation study by a panel of eight expert haematopathologists of how various histopathological features are used. Digital whole slide images of haematoxylin and eosin-stained sections allowed the pathologists to visually score cases independently as well as participate in virtual joint review conferences. Standardised consensus guidelines were formulated for scoring histopathological features and included overall architecture/growth pattern, presence or absence of a starry-sky pattern, cell size, nuclear pleomorphism, nucleolar prominence and a range of cytological characteristics. Despite the use of consensus guidelines, the results show a high degree of discordance among the eight expert pathologists. Approximately 50% of the cases lacked a majority score, and this discordance spanned all six histopathological features. Moreover, none of the histological variables aided in prediction of MYC single versus double/triple-hit or immunoglobulin-partner FISH-based designations or clinical outcome measures. Our findings indicate that there are no specific conventional morphological parameters that help to subclassify MYC-rearranged LBCL or select cases for FISH analysis, and that incorporation of FISH data is essential for accurate classification and prognostication.

Equine in vitro produced blastocysts: relationship of embryo morphology, stage and speed of development to foaling rate.

Information on factors associated with developmental competence of equine in vitro -produced (IVP) blastocysts is lacking. To determine the relationships of stage, grade, day of development, and specific morphological parameters of equine IVP blastocysts, to pregnancy and foaling rates. Photomicrographs of 316 IVP embryos with known pregnancy outcomes were scrutinised individually by four observers. Inter-observer variation was assessed, and pregnancy outcome evaluated in relation to day of blastocyst development and assigned grade and stage. Individual component analysis was performed to determine the association of specific morphological parameters with foaling rate. Overall pregnancy rate was 76.9% and foaling rate was 56.3%. The day of embryo development did not affect pregnancy rate but significantly affected foaling rate. Embryo stage did not affect foaling rate. Embryo grade affected foaling rate only for Day-9 embryos. Some morphological features in the bovine grading system did not predict outcome in equine IVP embryos. Significant individual parameters differed between Stage 5 and Stage 6 equine blastocysts. Day of blastocyst development is the major factor related to foaling rate for equine IVP embryos. Notably, there was no effect of embryo stage on foaling rate and no evidence that prolonging culture until embryos advance in stage increases foaling rate. The standard bovine grading system is not directly applicable to equine IVP embryos; equine-specific staging and grading systems are proposed. This information will allow laboratories to identify embryos with the highest developmental competence. Use of the proposed systems will increase consistency in embryo assessment among laboratories.

Automated apoptosis identification in fluorescence imaging of nucleus based on histogram of oriented gradients of high-frequency wavelet coefficients

The automatic and accurate identification of apoptosis facilitates large-scale cell analysis. Most identification approaches using nucleus fluorescence imaging are based on specific morphological parameters. However, these parameters cannot completely describe nuclear morphology, thus limiting the identification accuracy of models. This paper proposes a new feature extraction method to improve the performance of the model for apoptosis identification. The proposed method uses a histogram of oriented gradient (HOG) of high-frequency wavelet coefficients to extract internal and edge texture information. The HOG vectors are classified using support vector machine. The experimental results demonstrate that the proposed feature extraction method well performs apoptosis identification, attaining [Formula: see text] accuracy with low cost in terms of time. We confirmed that our method has potential applications to cell biology research.

Tuning protecto‐flexibility in nature: Case of the fish scale

AbstractFish scales are among the structural materials in nature that are inspiring the design and development of “next‐generation” engineering materials. Fish scales possess a mineralization gradient that divides their thickness into three unique regions, each containing characteristic structures and properties. Here, experiments and complementary numerical modeling are performed to understand the importance of the different geometrical and mechanical parameters affecting the structural behavior of fish scales. Numerical modeling results showed that the stiffness and work to fracture of the scales in flexure are dependent on the amplitude and wavelength of the limiting layer profile. Furthermore, the mechanical response in bending of the scales can be effectively tuned by the suture profile location within the limiting layer thickness. These results highlight the opportunity to tailor the mechanical response of flexible composite laminates through the architecture of the layers and their interfaces to effectively control the protecto‐flexibility.Key Points This work combines the disciplines of structural biology, materials science and mechanical engineering to identify the key contributions of the microstructure to the inherent protecto‐flexibility of fish scales, a class of natural dermal armor. The interdisciplinary approach enables an identification of how nature adjusts specific morphological parameters to modulate both flexiblity and protection from physical threats.

O-226 The microscopic se men improvement after surgical varicocele repair

Abstract Study question Evaluation of the effect of varicocele correction on conventional and microscopic seminal parameters and evaluation of which factors might predict sperm improvement after surgical treatment. Summary answer The detailed morphologic sperm evaluation has been identified as a novel parameter expressing the post-surgical semen amelioration after varicocelectomy. What is known already Generally, varicocele develops during puberty and occurs more often on the left side for anatomic reasons. However, its diagnosis is commonly delayed, especially in asymptomatic cases, until the man consults an andrologist for couple infertility. A causative relationship between varicocele and impairment of semen quality has been largely investigated in the context of male infertility. Despite the florid literature available on this topic, the clinical benefit in terms of semen quality improvement after varicocele surgical repair remains controversial. Study design, size, duration An observational, retrospective clinical trial was carried out including patients undergoing surgical treatment for varicocele at the Day Surgery of the Urology Operative Unit of the Santa Maria Nuova Hospital-IRCCS of Reggio Emilia from September 2011 to March 2020. Primary outcome was the detailed morphologic microscopic sperm evaluation. Secondary outcomes were conventional semen analyses. Each patient was considered two times (before and after the surgery) and evaluated by both physical examination and ultrasonography. Participants/materials, setting, methods The inclusion criteria considered the patients with diagnosis of varicocele at ultrasound examination, attending surgical resolution and with at semen analyses before and after the surgery, were excluded patients with diagnosis of varicocele without surgical indication, and/or semen analyses performed only before or only after the surgery. In the statistical analysis a logistic multivariate regression analysis was performed in order to evaluate the change before and after surgery. Main results and the role of chance The post-surgical semen analysis was performed after a mean of 183.7 + 112.5 days since the surgery for a total of 121 males (mean age 24.6 + 4.1 years) enrolled. The surgical treatment leads to a significant increase in sperm concentration (p = 0.015) and percentage of progressive and total motility (p = 0.022 and p = 0.039, respectively), with a significant decrease in the percentage of immobile sperms (p = 0.013). In particular, semen concentration improved in 71.7% of patients (p = 0.010). Considering the detailed morphologic microscopic evaluation, a significant improvement was detected: head abnormalities showed a significant reduction, considering microcephaly (3.3 + 3.6 versus 2.2 + 2.9%, p = 0.015), macrocephaly (1.4 + 0.6 versus 1.2 + 0.9%, p = 0.043) and cytoplasmic appendix (1.4 + 0.8 versus 0.9 + 1.2%, p = 0.041). Moreover, surgery led to a significant reduction of tails abnormalities, considering absence (0.6 +2.3 versus 0.1 + 0.7, p = 0.048) and coiled tail (5.2 + 1.5 versus 6.6 + 2.0, p = 0.037). Thus, surgical varicocele resolution leads to a significant improvement in specific morphological semen parameters. The multivariate logistic analysis identified the ultrasound varicocele degree before surgery as a main predictor of the sperm concentration improvement (p = 0.016). The semen parameters improvement was higher for varicocele of I and II degree (p = 0.008). Limitations, reasons for caution The retrospective study design precluded from carrying out a case-control study to compare the surgical techniques. Moreover, the study design limited the availability of patients’ clinical data in order to performed a more comprehensive predictive analysis. Wider implications of the findings Using a complex statistical approach, it emerged that the greatest improvement in semen quality was obtained in case of mild varicocele, increasing the knowledge on the therapeutic potential of surgery. This result has clinical implications, since it could help to select those patients ‘to treat or not to treat’. Trial registration number none

Novel cell-based analysis reveals region-dependent changes in microglial dynamics in grey matter in a cuprizone model of demyelination

Microglia are key players in Multiple Sclerosis (MS), expressing many susceptibility genes for this disease. They constantly survey the brain microenvironment, but the precise functional relationships between microglia and pathological processes remain unknown. We performed a detailed assessment of microglial dynamics in three distinct grey matter regions in a cuprizone-induced demyelination model. We found that microglial activation preceded detectable demyelination and showed regional specificities, such as prominent phagocytic activity in cortical layer 5 and early hypertrophic morphology in hippocampal CA1. Demyelination happened earliest in cortical layer 5, although was more complete in CA1. In cortical layer 2/3, microglial activation and demyelination were less pronounced but microglia became hyper-ramified with slower process movement during remyelination, thereby maintaining local brain surveillance. Profiling of microglia using specific morphological and motility parameters revealed region-specific heterogeneity of microglial responses in the grey matter that might serve as sensitive indicators of progression in CNS demyelinating diseases.

Impact of seasonal variations on antidiabetic phytochemicals in Alstonia scholaris

Background and Aim: Plants live on a planet with days and seasons, and that affects their phytoconstituents. Challenge is, availability of active principles in medicinal plants change by seasonal fluctuations, so their dose pattern for therapeutic efficacy also gets influenced. The best duration for the harvesting of specific secondary metabolites for better yield is not fixed. Seasonal impact show changes in important constituents like polyphenol, flavonoids, glycosides, alkaloids, essential oil etc. Late summer is the best collection time for essential oil component. Winter and rainy are best season for other secondary metabolites. Experimental procedure: The selected plant i.e. Alstonia scholaris L., belongs to alkaloidal category with having antidiabetic activity. Plants were evaluated for pharmacognostic study which includes macroscopic and microscopic evaluation, determination of physicochemical parameters in a systematic way. HPTLC fingerprinting for erythrodiol was done. Study was performed for plant material with three different seasons and best results were analysed. Results and Conclusion: All the plants showed correct taxonomy with specific morphological, microscopical and physico-chemical parameters which is helpful for the standardization of drugs. Extracts showed presence of alkaloids, terpenes, flavonoids, steroids, phenolics, saponin and carbohydrate. HPTLC fingerprinting confirmed the presence of erythradiol in the plant extracts. Seasonal variations occour in plant constituent shows best collection period. Current research aims to focus on best possible season for the harvesting of some pharmaceutically important plant materials.

Towards Characterizing and Developing Formation and Migration Cues in Seafloor Sand Waves on Topology, Morphology, Evolution from High-Resolution Mapping via Side-Scan Sonar in Autonomous Underwater Vehicles.

Sand waves constitute ubiquitous geomorphology distribution in the ocean. In this paper, we quantitatively investigate the sand wave variation of topology, morphology, and evolution from the high-resolution mapping of a side scan sonar (SSS) in an Autonomous Underwater Vehicle (AUV), in favor of online sequential Extreme Learning Machine (OS-ELM). We utilize echo intensity directly derived from SSS to help accelerate detection and localization, denote a collection of Gaussian-type morphological templates, with one integrated matching criterion for similarity assessment, discuss the envelope demodulation, zero-crossing rate (ZCR), cross-correlation statistically, and estimate the specific morphological parameters. It is demonstrated that the sand wave detection rate could reach up to 95.61% averagely, comparable to deep learning such as MobileNet, but at a much higher speed, with the average test time of 0.0018 s, which is particularly superior for sand waves at smaller scales. The calculation of morphological parameters primarily infer a wave length range and composition ratio in all types of sand waves, implying the possible dominant direction of hydrodynamics. The proposed scheme permits to delicately and adaptively explore the submarine geomorphology of sand waves with online computation strategies and symmetrically integrate evidence of its spatio-temporal responses during formation and migration.

Assessing the rockfall protection efficiency of forests at the regional scale

The aim of this paper is to achieve a quantitative assessment of rockfall protection forest efficiency at regional scale, considering site specific forest, morphological and lithological parameters. At first, a semi-automatic GIS-based method, integrated with a multi-scenario 3D-rockfall model realized by using the simulation code HY-STONE, was used to map protection forests of Regione Lombardia (central Italian Alps). For each different forest type, a rockfall protective efficiency was assessed by using empirical (energy line angle) and modelling (HY-STONE) approaches. The empirical approach shows an increase of the energy line angle value from about 36° for the bare slopes to over 40° in forested slopes, with a value ranging from 37° to 44° for different forests types. The modelling approach is based on a new efficiency index EEI ranging from 0 (minimum efficiency, equal to no forest condition) to 1 (maximum efficiency): the efficiency of different forest types ranges from 0.08 to 0.98 by using average values of the controlling parameters. To modulate the efficiency in each single forest at regional scale, a set of parametric simulations was performed to evaluate the effects of controlling parameters. The parametric simulations show that block volume, slope gradient, DBH (diameter at breast height) and forest density are the most important parameters at controlling the efficiency. These parameters were used within a multiple linear regression function to associate a protection efficiency to each specific protection forest in the regional map. This allows to discriminate quantitatively the individual forests according to their actual efficiency. Most of the protection forest area (46%) shows an efficiency greater than 0.50 and only the 24% of the total covered area shows a value lower than 0.25.

Optimal process design space to ensure maximum viability and productivity in Penicillium chrysogenum pellets during fed-batch cultivations through morphological and physiological control

BackgroundBiomass growth of Pencillium chrysogenum is characterised by a distinct pellet morphology consisting of compact hyphal agglomerates. Fungal pellets are advantageous in industrial process control due to rheological advantages but lead to biomass degradation due to diffusional limitations of oxygen and substrate in the pellet’s core. Several fermentation parameters are known to affect key pellet characteristics regarding morphology, viability and productivity. Pellet morphology and size are affected by agitation. Biomass viability and productivity are tightly interlinked with substrate uptake and dissolved oxygen concentration.ResultsThe goal of this study was to study the impact of the fermentation parameters power input, dissolved oxygen content and specific substrate uptake rate on morphology, biomass viability and productivity. A design of experiments (DoE) approach was conducted and corresponding responses were analysed using novel morphological descriptors analysed by a previously established flow cytometry method. Results clearly display inverse correlations between power input and pellet size, specific morphological parameters related to pellet density can be increased in direct proportion to power input. Biomass viability and productivity are negatively affected by high specific substrate uptake rates.ConclusionsBased upon multiple linear regression, it was possible to obtain an optimal design space for enhanced viability and productivity at beneficial morphological conditions. We could maintain a high number of pellets with favourable morphology at a power input of 1500 W/m3. A sound compromise between viability and high productivity is possible at a specific glucose uptake rate of 0.043 g/g/h at dissolved oxygen levels of 40% minimum.

Morphological and physiological changes during maturation of okra seeds evaluated through image analysis

ABSTRACT: This study was performed to associate specific morphological parameters, defined by X-ray images, with seed performance of okra (Abelmoschus esculentus (L.) Moench) during maturation. Fruits of cultivar Santa Cruz 47 at different developmental stages were collected at five-day intervals (from 5 to 65 days after anthesis) and water content, dry matter, germination and vigor were determined in seeds extracted immediately after each harvest or after temporary storage for seven days. X-ray tests were also performed after each harvest and the images were analyzed by ImageJ® software to produce data of aspect ratio (relation between major and minor axes of the ellipse surrounding the seed perimeter) and percentage of free space area in the inner seed cavity. Physiological maturity (maximum accumulation of dry matter) was reached at 30 days after anthesis (DAA), when seed water content was 56.6 %. Seed germination and vigor increased during maturation, achieving the maximum at 50 DAA. Seeds showed morphological changes during maturation, becoming more spherical (aspect ratio near 1.0); at the same time, the free space available in the inner cavity of the seed decreased. This parameter can be successfully used as a marker of physiological maturity when values equal or lower than 5 % are reached.

P5249Comprehensive invasive and non-invasive assessment of coronary artery lesions with and without hemodynamic significance

Abstract Background There is limited knowledge about specific morphological parameters beyond the degree of stenosis to further characterize hemodynamically relevant coronary lesions. Objective The goal of this study was to identify certain morphological or molecular characteristics that distinguish hemodynamically significant from non-significant coronary lesions using various invasive and non-invasive measures. Methods This clinical study included patients with symptoms suggestive of CAD who underwent native T1-weighted CMR and gadofosveset-enhanced CMR as well as invasive coronary angiography between 2015 and 2016. OCT of the culprit vessel to determine the plaque type was performed in a subset of patients. Functional relevance of all lesions was examined using quantitative flow reserve (QFR-Angio). Hemodynamically significant lesions were defined as lesions with a QFR &lt;0.8. Signal intensity (contrast-to-noise ratios; CNRs) on native T1-weighted CMR and gadofosveset-enhanced CMR was defined as a measure for intraplaque hemorrhage and endothelial permeability respectively. Results Overall 13 patients (n=28 coronary segments) were included, whose invasive coronary angiograms projections were eligible for QFR analysis. Segments containing lesions with a QFR &lt;0.8 (n=9) were associated with significantly higher signal enhancement on Gadofosveset-enhanced CMR as compared to segments containing a hemodynamically non-relevant lesions (lesion-QFR&gt;0.8; n=19) (7.0±4.9 vs. 3.0±2.6; p=0.02). No differences in signal enhancement were seen on native T1-weighted CMR (2.1±4.3 vs. 3.3±4.1; p=0.24). 66,7% (4 out of 6) of all vulnerable plaque and 33.3% (2 out of 6) of all non-vulnerable plaque (fibroatheroma) as assessed by OCT were hemodynamically significant lesions. Conclusion The findings of this small feasibility study suggest that hemodynamically significant lesions are more advanced and associated with a higher grade of endothelial permeability while the presence of intraplaque hemorrhage may not be associated with hemodynamically relevant coronary lesions.

Noninvasive Follicular Thyroid Neoplasm with Papillary-Like Nuclear Features (NIFTP): Update and Diagnostic Considerations-a Review.

Advances in our understanding of thyroid lesions, especially those entities with an indolent behavior, has led clinicians to question the most appropriate surgical management of such thyroid nodules. Several studies have shown that the non-invasive encapsulated follicular variant of papillary thyroid carcinomas (NI-EFVPC) exhibits poor histopathologic diagnostic reproducibility and have been over-treated as conventional thyroid cancer. In 2015, an international thyroid working group re-evaluated NI-EFVPC and its diagnostic criteria. The new terminology of "noninvasive follicular thyroid neoplasm with papillary-like nuclear features" (NIFTP) was accordingly introduced to replace NI-EFVPC. The literature has emphasized that NIFTPs are biologically similar to follicular adenomas lacking lymph node metastases and/or recurrence. While the definition of NIFTP is based on specific morphological parameters, recent studies have questioned whether the criterion allowing less than 1% of true papillae should be revised to a total absence of papillae. The motivation for this revision is the rare finding, in some studies, of lymph nodes with metastatic NIFTP. This review evaluates the existing published series of NIFTP cases, clinical consequences of NIFTP, and emerging changes in the diagnostic criteria for NIFTP. The introduction of NIFTP has resulted in significant impact on the clinical management of thyroid nodules. Recent revisions in the morphological criteria for NIFTP emphasize the need to adhere to very stringent histomorphologic criteria when making a diagnosis of NIFTP. The adoption of NIFTP terminology instead of NI-EFVPC is associated with conservative lobectomy without radioactive iodine treatment in the majority of cases.

Computation of hemodynamics in eccentric coronary stenosis: A morphological parametric study.

Flow recirculation occurs in eccentric coronary stenosis, which can lead to adverse outcome. The complex local geodesic patterns of eccentric stenosis are critical factors in determining the flow characteristics in post-stenotic flow. The main objective of this study is to relate the relationship between the detailed morphological parameters in eccentric coronary stenosis and the post-stenotic flow characteristics. Several idealized eccentric coronary stenosis models with variable morphological parameters are created to conduct a series of computational fluid dynamics analysis. The impact of four specific lesion morphological parameters, eccentricity index (EI), diameter stenosis (DS), stenosis length (SL) and shape of lesion, are investigated. When EI is small (< 0.33), the length of recirculation zones would increase as EI increase; while when EI is large (> 0.33), it would decreased as EI increase; Larger magnitude of retrograde flow occurs in models with smaller EIs. Both the recirculation zone length and maximum shear rate increase significantly as DS increases. Increase of SL will lead to increase of recirculation zone length. Higher maximum shear rate and larger recirculation zone are observed in models with sharper stenosis shape. Except DS, the detailed geometry patterns (EI, SL and shape of the stenosis) also have great impact on post-stenotic flow behaviors in eccentric coronary stenosis.

Recent advances in controlled modification of the size and morphology of metal-organic frameworks

Advances in metal-organic frameworks (MOFs) resulted in significant contributions to diverse applications such as carbon capture, gas storage, heat transformation and separation along with emerging applications toward catalysis, medical imaging, drug delivery, and sensing. The unique in situ and ex situ structural features of MOFs can be tailored by conceptual selection of the organic (e.g., ligand) and inorganic (e.g., metal) components. Here, we provide a comprehensive review on the synthesis and characterization of MOFs, particularly with respect to controlling their size and morphology. A better understanding of the specific size and morphological parameters of MOFs will help initiate a new era for their real-world applications. Most importantly, this assessment will help develop novel synthesis methods for MOFs and their hybrid/porous materials counterparts with considerably improved properties in targeted applications.

Abstract C39: High-content screening to capture tumor dynamics in response to microenvironmental perturbations

Abstract Tumor populations are in constant flux as a result of dynamic pressures of their surrounding microenvironment. Measuring the phenotypic response of multiple cell types exposed to physiological relevant tumor conditions has been a challenge due to the heterogenous nature of the tumor microenvironment. Further, traditional cell biology assays for assessing cell viability do not allow for additional downstream analyses and use surrogate measures for cell number, which may fail to provide a complete picture of cellular events. Here, we present a method to utilize high-content screening to generate quantitative, robust data sets characterizing cellular phenotypic responses (i.e. birth, death, morphology) of tumor cells to co-occurring perturbations of drug, oxygen, glucose, ECM stiffness, and stromal cell co-culture. Using an Operetta high-content imaging platform, we are able to perform multiple analyses on the same experimental setup to quantitatively assess the evolutionary dynamics of heterogenous cell populations under multiple environmental perturbations. We are able to differentiate between the effect of microenvironmental conditions on a decrease in cell birth versus increase in cell death, which has significant implications for predicting tumor growth kinetics and drug treatment response. We applied this platform to analyze isogenic lung tumor cells that are either sensitive or resistant to erlotinib, a commonly used tyrosine receptor kinase inhibitor in the treatment of lung cancer. We identified specific microenvironmental contexts where the resistant populations have a fitness advantage over the sensitive population, irrespective of the resistance mechanism. Furthermore, our experimental workflow allows us to capture and quantify cell morphology, an additional measure for overall cell health. We observed significant shifts in specific cell morphological parameters in response to alterations in tumor microenviromental conditions such as low oxygen and increased drug concentration. This novel application of a high-content screening platform allows for the quantification of multiple cellular phenotypes in response to over a hundred different microenvironmental contexts, thus providing deeper insight into the effect of tumor microenvironmental heterogeneity on evolving tumor cell populations. Citation Format: Colleen M. Garvey, Oscar Chen, Jasmine Foo, Shannon M. Mumenthaler. High-content screening to capture tumor dynamics in response to microenvironmental perturbations. [abstract]. In: Proceedings of the AACR Special Conference: Function of Tumor Microenvironment in Cancer Progression; 2016 Jan 7–10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2016;76(15 Suppl):Abstract nr C39.