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With their role in connecting disease-associated antigens to the cellular immune response, antibodies hold considerable promise as therapeutic agents. This chapter discusses three classes of therapeutic antibodies that have been developed for use in ovarian cancer therapy. The first includes antibodies selected against tumor-associated antigens such as MUC16/CA125, mesothelin, epithelial cell adhesion molecule, and folate receptor α‎. Antibodies in the second class target proteins such as CTLA-4 and PD1 that act as immune response checkpoint receptors. The third class of antibodies target secreted factors that promote tumor growth: targets in this class include vascular endothelial growth factor, cytokines, and chemokines. The development of each of these is described. The chapter also discusses the complications presented by soluble antigens, which serve to limit the applicability of antigens (such as MUC16/CA125) that are both cell-surface associated and circulating and the prospects for the combination of antibody-based immunotherapy and chemotherapy.

Aerobic glycolysis is an important metabolic adaptation of cancer cells. There is growing evidence that oxidative phosphorylation is also an active metabolic pathway in many tumors, including in high grade serous ovarian cancer. Metastasized ovarian tumors use fatty acids for their energy needs. There is also evidence of ovarian cancer stem cells privileging oxidative phosphorylation (OXPHOS) for their metabolic needs. Metformin and thiazolidinediones such as rosiglitazone restrict tumor growth by inhibiting specific steps in the mitochondrial electron transport chain. These observations suggest that strategies to interfere with oxidative phosphorylation should be considered for the treatment of ovarian tumors. Here, we review the literature that supports this hypothesis and describe potential agents and critical control points in the oxidative phosphorylation pathway that can be targeted using small molecule agents. In this review, we also discuss potential barriers that can reduce the efficacy of the inhibitors of oxidative phosphorylation.

This chapter uses a systems approach to represent the healthcare sector and positions safety reporting programs as feedback mechanisms to reactively, proactively, and predictively improve the overall reliability and safety of care practices. Drawing from the aviation sector, benefits and limitations of different safety reporting systems are explored and challenges to adapting such systems into healthcare are presented. Examples of successful adaptation and implementation in healthcare demonstrate that while adaptation is possible and could yield impressive outcomes, such programs remain susceptible to the natural tendency of the healthcare system to remain siloed and internally competitive, rather than holistic and team-oriented. Thus, one could conclude that in order for safety reporting programs to be self-sustaining, the systemic disincentives need to be examined carefully and intentionally removed, replacing them with meaningful incentives to collaboration and maximization of patient safety outcomes.

The social interaction among people is always influenced by human face. The complex characteristics of human face are gender, emotions, identity, etc. In this world of visual technology, the challenge lies in automatic extraction of these facial characteristics. Hence research in this area has broad applications in biometric authentication, surveillance systems, human-computer interface, etc. This paper focuses on gender classification using face images. In proposed paper, deep learning based gender classification approach is used. In this paper, six prominent face regions are extracted using Haar classifier. These extracted face regions are then learned using deep learning architecture. The experimental results shows accuracy from 99.4% under various artifacts such as illumination variation, pose variation which are inherent in most of unconstrained environment. The database used is Psychological Image Collection at Stirling (PICS) 2D face database of Aberdeen.

Smartphone-based clients are being increasingly used in a medical world for individual as well as group communications. The authors report the use of WhatsApp, a common social media smartphone client for neurosurgical referral service in their Institution. They extend the use of WhatsApp application from a purely intra-departmental informal communication to a formal tertiary referral service for Neurosurgical referrals. The pros and cons of deploying such system are discussed and important concerns are highlighted.Over a period of one year, the authors record 1412 referrals to the Neurosurgical service at a tertiary referral centre using WhatsApp application. All the data gathered through WhatsApp referrals was subsequently validated and analysed for any errors. They identify eight incidences where the system did not accurately convey the intended information. They highlight the potential issues related to data accuracy and confidentiality encountered in using such a system.In this preliminary study, the authors consider WhatsApp application as an important tool for Neurosurgical referrals. It is safe, cheap, reliable and user-friendly application allowing seamless transfer of data including clinical videos and scan images to the on call neurosurgical team. Loss of data quality, concerns surrounding patient confidentiality, errors caused by inter-operator variability in capturing data and default prohibition of use of such social media applications in many institutions are important disadvantages in regularly using such service.Smartphone-based social media clients such as WhatsApp provide a promising future for faster, reliable communication of clinical and radiological data, which can be used for on-call neurosurgical referrals. Integration with PACs applications and facial recognition may facilitate increasing use of such applications in future addressing many of the concerns that currently prohibit their universal use.

The use of steel material in all various types of engineering field industry has more interest in theory, analysis, design and manufacturing of structural components made of steel materials. This paper present a technique to determine deformation of steel plate using Welch's Periodogram estimate. The experimental setup consist of free ball impact testing setup, piezoelectric type accelerometer i.e. MIL 521, data acquisition device i.e. NI cDAQ-9234. The vibration signal induced due to impact of free falling ball at different heights. The signals are acquired using piezoelectric accelerometer and data is process using cDAQ card. The fundamental natural frequency is capture using Welch's Periodogram and FFT. The deformation of steel plate is obtain using fundamental natural frequency. The experimentation is performed at various heights using impact testing setup. It is observed that fundamental natural frequency remains nearly constant under various impact energy.

Handwritten script identification and converting it to printed electronic document as vast application. It helps to translate humanly readable to machine-readable text. This paper presents a technique to identify non cursive scanned, handwritten English script to digital document in notepad/MS-Office format using neural networks. Initially preprocessing of the input document image as conversion from RGB image to 8 bit gray scale, nonlinear contrast enhancement and mean normalization for correcting non uniform illumination and binarization are performed. Further the lines, words and characters of the input documents are localized in the preprocessed image and extracted from gray input image. Each extracted character of the gray input image is resized, normalized and used as input to the neural network for classification. The network consists of two layers feedforward network with sigmoid output neurons. The error back propagation algorithm is used for training. The proposed technique is tested on sample images from publically available CEDAR database as well as self created database with 1600 images for training and 620 images for testing purpose belonging to 62 classes. Overall Recognition accuracy of 95% is obtained. The performance of the proposed technique is also compared with the other existing technique.

We report on results of fifth harmonic generation in Cesium Lithium Borate (CLBO) using a three-crystal cascaded frequency conversion scheme designed to study the energy balance of the final sum frequency generation stage. The experimental setup independently combines the first and fourth harmonic of a Nd:Glass laser in a 5mm thick CLBO crystal. Energy balance between the incoming and output energy is close to unity when the CLBO is out of phase matching and approximately 80p when the crystal is in phase matching. A detailed analysis of the residual fundamental and fourth harmonic energy indicates 5th harmonic light is being generated but only 26p is unaccounted for. We attribute the missing light to linear transmission loss in the CLBO oven. The ratio of the output to input energy is unity when the missing 5th harmonic is incorporated into the calculations. Two-dimensional plane wave mixing simulations show agreement with the results at lower intensities.

Plumbagin, an anti-cancer agent, is toxic to cells of multiple species. We investigated if plumbagin targets conserved biochemical processes. Plumbagin induced DNA damage and apoptosis in cells of diverse mutational background with comparable potency. A 3–5 fold increase in intracellular oxygen radicals occurred in response to plumbagin. Neutralization of the reactive oxygen species by N-acetylcysteine blocked apoptosis, indicating a central role for oxidative stress in plumbagin-mediated cell death. Plumbagin docks in the ubiquinone binding sites (Q0 and Qi) of mitochondrial complexes I–III, the major sites for oxygen radicals. Plumbagin decreased oxygen consumption rate, ATP production and optical redox ratio (NAD(P)H/FAD) indicating interference with electron transport downstream of mitochondrial Complex II. Oxidative stress induced by plumbagin triggered an anti-oxidative response via activation of Nrf2. Plumbagin and the Nrf2 inhibitor, brusatol, synergized to inhibit cell proliferation. These data indicate that while inhibition of electron transport is the conserved mechanism responsible for plumbagin’s chemotoxicity, activation of Nrf2 is the resulting anti-oxidative response that allows plumbagin to serve as a chemopreventive agent. This study provides the basis for designing potent and selective plumbagin analogs that can be coupled with suitable Nrf2 inhibitors for chemotherapy or administered as single agents to induce Nrf2-mediated chemoprevention.

Silicon substance (is also known as Quartz) is an abundant in nature and the electrical properties it exhibits, plays a vital role in developing its usage in the field of semiconductor. More than decades we can say that Silicon has shown desirable signs but at the later parts it has shown some research potential for development of alternative material as semiconductor devices. This need has come to light as we started scaling down in size of the Silicon material and up in speed. This semiconductor material started exhibiting several fundamental physical limits that include the minimum gate oxide thickness and the maximum saturation velocity of carriers which determines the operation frequency. Though the alternative semiconductors provide some answers (such as III-V’s for high speed devices) for a path to skirt these problems, there also may be some ways to extend the life of silicon itself. Two paths are used as for alternative semiconductors i.e alternative gate dielectrics and silicon-based heterostructures. The SiC material has some strength properties under different conditions and find out the defects available in the material.Silicon substance (is also known as Quartz) is an abundant in nature and the electrical properties it exhibits, plays a vital role in developing its usage in the field of semiconductor. More than decades we can say that Silicon has shown desirable signs but at the later parts it has shown some research potential for development of alternative material as semiconductor devices. This need has come to light as we started scaling down in size of the Silicon material and up in speed. This semiconductor material started exhibiting several fundamental physical limits that include the minimum gate oxide thickness and the maximum saturation velocity of carriers which determines the operation frequency. Though the alternative semiconductors provide some answers (such as III-V’s for high speed devices) for a path to skirt these problems, there also may be some ways to extend the life of silicon itself. Two paths are used as for alternative semiconductors i.e alternative gate dielectrics and silicon-based heterostruc...

The goal of this study was to investigate the anti-cancer effects of Trans10,cis12 conjugated linoleic acid (t10,c12 CLA). MTT assays and QCM™ chemotaxis 96-wells were used to test the effect of t10,c12 CLA on the proliferation and migration and invasion of cancer cells. qPCR and Western Blotting were used to determine the expression of specific factors. RNA sequencing was conducted using the Illumina platform and apoptosis was measured using a flow cytometry assay. t10,c12 CLA (IC50, 7 μM) inhibited proliferation of ovarian cancer cell lines SKOV-3 and A2780. c9,t11 CLA did not attenuate the proliferation of these cells. Transcription of 165 genes was significantly repressed and 28 genes were elevated. Genes related to ER stress, ATF4, CHOP, and GADD34 were overexpressed whereas EDEM2 and Hsp90, genes required for proteasomal degradation of misfolded proteins, were downregulated upon treatment. While apoptosis was not detected, t10,c12 CLA treatment led to 9-fold increase in autophagolysosomes and higher levels of LC3-II. G1 cell cycle arrest in treated cells was correlated with phosphorylation of GSK3β and loss of β-catenin. microRNA miR184 and miR215 were upregulated. miR184 likely contributed to G1 arrest by downregulating E2F1. miR215 upregulation was correlated with increased expression of p27/Kip-1. t10,c12 CLA-mediated inhibition of invasion and migration correlated with decreased expression of PTP1b and decreased Src activation by inhibiting phosphorylation at Tyr416. Due to its ability to inhibit proliferation and migration, t10,c12 CLA should be considered for treatment of ovarian cancer.

Retinal image registration is a necessary step in diagnosis and monitoring of Diabetes Retinopathy (DR), which is one of the leading causes of blindness. Long term diabetes affects the retinal blood vessels and capillaries eventually causing blindness. This progressive damage to retina and subsequent blindness can be prevented by periodic retinal screening. The extent of damage caused by DR can be assessed by comparing retinal images captured during periodic retinal screenings. During image acquisition at the time of periodic screenings translation, rotation and scale (TRS) are introduced in the retinal images. Therefore retinal image registration is an essential step in automated system for screening, diagnosis, treatment and evaluation of DR. This paper presents an algorithm for registration of retinal images using orthogonal moment invariants as features for determining the correspondence between the dominant points (vessel bifurcations) in the reference and test retinal images. As orthogonal moments are invariant to TRS; moment invariants features around a vessel bifurcation are unaltered due to TRS and can be used to determine the correspondence between reference and test retinal images. The vessel bifurcation points are located in segmented, thinned (mono pixel vessel width) retinal images and labeled in corresponding grayscale retinal images. The correspondence between vessel bifurcations in reference and test retinal image is established based on moment invariants features. Further the TRS in test retinal image with respect to reference retinal image is estimated using similarity transformation. The test retinal image is aligned with reference retinal image using the estimated registration parameters. The accuracy of registration is evaluated in terms of mean error and standard deviation of the labeled vessel bifurcation points in the aligned images. The experimentation is carried out on DRIVE database, STARE database, VARIA database and database provided by local government hospital in Pune, India. The experimental results exhibit effectiveness of the proposed algorithm for registration of retinal images.

Facial identication is important these days, Methods are required must be fast and accurate enough to work realtime. So research in methods for face recognition seems ever growing. The measurements of an individuals data is inherent part of FR techniques. In biomedical verification and identification requires the dataset such as iris, finger prints etc. While for FR, cameras are replacing the cards at places like ATMs. It helps capturing facial images of customers, and compare these photos to the images of account holders database of banks to verify the customers identity. This paper proposes way for face recognition. Shape and texture of facial images are studied for representation. The face is Firstly divided into tiny regions. Which are used to get LBPH. These histograms merged in one partially enhanced histogram, by which we get face images effciently. KNN classier does the classication and not just effciency but the simplicity of manner allows very fast feature extraction.

We report a new method using high-stability, laser-driven supercontinuum generation in a liquid cell to calibrate the absolute photon response of fast optical streak cameras as a function of wavelength when operating at fastest sweep speeds. A stable, pulsed white light source based around the use of self-phase modulation in a salt solution was developed to provide the required brightness on picosecond time scales, enabling streak camera calibration in fully dynamic operation. The measured spectral brightness allowed for absolute photon response calibration over a broad spectral range (425-650 nm). Calibrations performed with two Axis Photonique streak cameras using the Photonis P820PSU streak tube demonstrated responses that qualitatively follow the photocathode response. Peak sensitivities were one photon/count above background. The absolute dynamic sensitivity is less than the static by up to an order of magnitude. We attribute this to the dynamic response of the phosphor being lower.

Composite materials have beneficial uses in Aerospace, Structural engineering particularly in weight reduction in the finished part. For that reason, harmonic analysis has been the topic of intensive research. This paper aims to carry out an algorithm for natural frequency and deformation of composite plate by vibration signal analysis. The vibration signal is measured using piezoelectric type accelerometer. The ARX model and FFT of the signal is simulated using MATLAB. Natural frequency is used to calculate the deformation of the plate. The results are validated with finite element method.

Motion estimation and tracking are significant activities in many computer vision applications. Real-time surveillance is a vigorous element in any circumstances or environment where there is a great necessity of security for both personal and commercial property and assets. This paper aims to develop a prototype for measurement of vehicle speed. The vehicle speed is estimated using algorithm based on background modeling and blob detection. Absolute differencing method isolates foreground and background efficiently. The blob detection technique provides coordinates in the form of centroid resulting in the display of the vehicle movement. The performance of the system has been tested on videos captured on typical Indian highways using AXIS IP camera. Also, the algorithm is tested in the lab setup. A Raspberry Pi 3 processor and IP camera were used as hardware for this project. To overcome the shortcoming of formerly recommended methodologies, here vehicle speed estimation is done in Python using OpenCV. The speed is calculated by mathematical formulation based on the distance traversed by vehicle. The error in the speed estimation is observed to be 9 %.

Development of automated system for vehicle speed measurement is main feature to solve the problem regarding to the traffic surveillance system. It is profitable for secure transportation, avoiding the road accidents etc. There are plentiful technologies or methods developed for speed measurement but to moderate drawbacks of earliest methods, in this paper, we are following key steps such as background modeling, foreground detection and vehicle tracking. This paper presents a technique for vehicle speed measurement and vehicle tracking. The vehicle speed is estimated using system based on background modelling whereas Vehicle tracking have been achieved with the help of blob detection through all frames. This system is flexible and extended for other applications. The speed has been calculated by mathematical formulation based on the number of frames, frame rate & distance traversed by vehicle. This experiment was performed on different type of vehicles and different range of speed.

We report measurements of optical absorption in the zigzag antiferromagnet α-RuCl_{3} as a function of temperature T, magnetic field B, and photon energy ℏω in the range ∼0.3-8.3 meV, using time-domain terahertz spectroscopy. Polarized measurements show that threefold rotational symmetry is broken in the honeycomb plane from 2 to 300 K. We find a sharp absorption peak at 2.56 meV upon cooling below the Néel temperature of 7 K at B=0 that we identify as the magnetic-dipole excitation of a zero-wave-vector magnon, or antiferromagnetic resonance (AFMR). With the application of B, the AFMR broadens and shifts to a lower frequency as long-range magnetic order is lost in a manner consistent with transitioning to a spin-disordered phase. From a direct, internally calibrated measurement of the AFMR spectral weight, we place an upper bound on the contribution to the dc susceptibility from a magnetic excitation continuum.

Ovarian cancer remains the most deadly gynecological cancer with a poor aggregate survival rate. To improve upon this situation, we utilized collagen-specific Second Harmonic Generation (SHG) imaging microscopy and optical scattering measurements to probe structural differences in the extracellular matrix of normal stroma, benign tumors, endometrioid tumors, and low and high-grade serous (LGS and HGS) tumors. The SHG signatures of the emission directionality and conversion efficiency as well as the optical scattering are related to the organization of collagen on the sub-micron size. The wavelength dependence of these readouts adds additional characterization of the size and distribution of collagen fibrils/fibers relative to the interrogating wavelengths. We found strong wavelength dependent dependencies of these metrics that were different between the different tumors that are related to respective structural attributes in the collagen organization. These sub-resolution determinations are consistent with the dualistic classification of type I and II serous tumors. However, type I endometrioid tumors have strongly differing ECM architecture than the serous malignancies. Moreover, our analyses are further consistent with LGS and benign tumors having similar etiology. We identified optimal wavelengths for the SHG metrics as well as optical scattering measurements. The SHG metrics and optical scattering measurements were then used to form a linear discriminant model to classify the tissues, and we obtained high accuracy (~90%) between the tissue types. This delineation is superior to current clinical performance and has potential applicability in supplementing histological analysis, understanding the etiology, as well as development of an in vivo screening tool.

We report on the detection of the time-dependent B-field amplitude and topology in a laser-driven solenoid. The B-field inferred from both proton deflectometry and Faraday rotation ramps up linearly in time reaching 210 ± 35 T at the end of a 0.75-ns laser drive with 1 TW at 351 nm. A lumped-element circuit model agrees well with the linear rise and suggests that the blow-off plasma screens the field between the plates leading to an increased plate capacitance that converts the laser-generated hot-electron current into a voltage source that drives current through the solenoid. ALE3D modeling shows that target disassembly and current diffusion may limit the B-field increase for longer laser drive. Scaling of these experimental results to a National Ignition Facility (NIF) hohlraum target size (∼0.2cm^{3}) indicates that it is possible to achieve several tens of Tesla.

Background Ovarian cancer remains the most deadly gynecological cancer with a poor aggregate survival rate; however, the specific rates are highly dependent on the stage of the disease upon diagnosis. Current screening and imaging tools are insufficient to detect early lesions and are not capable of differentiating the subtypes of ovarian cancer that may benefit from specific treatments. Method As an alternative to current screening and imaging tools, we utilized wavelength dependent collagen-specific Second Harmonic Generation (SHG) imaging microscopy and optical scattering measurements to probe the structural differences in the extracellular matrix (ECM) of normal stroma, benign tumors, endometrioid tumors, and low and high-grade serous tumors. Results The SHG signatures of the emission directionality and conversion efficiency as well as the optical scattering are related to the organization of collagen on the sub-micron size scale and encode structural information. The wavelength dependence of these readouts adds additional characterization of the size and distribution of collagen fibrils/fibers relative to the interrogating wavelengths. We found a strong wavelength dependence of these metrics that are related to significant structural differences in the collagen organization and are consistent with the dualistic classification of type I and II serous tumors. Moreover, type I endometrioid tumors have strongly differing ECM architecture than the serous malignancies. The SHG metrics and optical scattering measurements were used to form a linear discriminant model to classify the tissues, and we obtained high accuracy (>90%) between high-grade serous tumors from the other tissue types. High-grade serous tumors account for ~70% of ovarian cancers, and this delineation has potential clinical applications in terms of supplementing histological analysis, understanding the etiology, as well as development of an in vivo screening tool. Conclusions SHG and optical scattering measurements provide sub-resolution information and when combined provide superior diagnostic power over clinical imaging modalities. Additionally the measurements are able to delineate the different subtypes of ovarian cancer and may potentially assist in treatment protocols. Understanding the altered collagen assembly can supplement histological analysis and provide new insight into the etiology. These methods could become an in vivo screening tool for earlier detection which is important since ovarian malignancies can metastasize while undetectable by current clinical imaging resolution.

We report the first complete set of measurements of a laser-plasma optical system's refractive index, as seen by a second probe laser beam, as a function of the relative wavelength shift between the two laser beams. Both the imaginary and real refractive index components are found to be in good agreement with linear theory using plasma parameters measured by optical Thomson scattering and interferometry; the former is in contrast to previous work and has implications for crossed-beam energy transfer in indirect-drive inertial confinement fusion, and the latter is measured for the first time. The data include the first demonstration of a laser-plasma polarizer with $85%--87%$ extinction for the particular laser and plasma parameters used in this experiment, complementing the existing suite of high-power, tunable, and ultrafast plasma-based photonic devices.

Background Soft tissue defects over the mid- and distal third tibia, heel, dorsum and plantar aspect of the foot and over the medial, lateral and posterior aspect of the ankle are a common scenario in clinical orthopaedic practice. In this article, we describe the utility of the reverse sural fasciocutaneous flap with a cutaneous pedicle in 109 clinical cases with distal lower limb soft tissue defects. Materials and methods A total of 109 patients were operated on for moderate (5–15 cm) and large (more than 15 cm) soft tissue defects at various sites along the lower limb including foot, heel and sole with the reverse sural fasciocutaneous flap. The defects were secondary to trauma (61 cases), diabetic ulcers (12 cases), post-traumatic scar contracture (8 cases), venous ulcer (4 cases), wound dehiscence (10 cases), leprotic non-healing ulcer (1 case), post-infective wound (1 case), radiation-induced ulcer following radiotherapy for synovial cell sarcoma (1 case), post-fibromatosis excision (1 case), post-dermatofibrosarcoma excision (1 case), post-heel melanoma excision (1 case) and actinomycosis foot (1 case). Patients were assessed for flap uptake and healing of defects. Results Among the 102 cases analysed, 81 were male and 21 female with an average age of 32.7 years. The average size of the flaps was 148.10 ± 59.54 cm2. The flap healed uneventfully in 89.21 % of patients. Edge necrosis occurred in 9 cases. Donor site regrafting was required in 7 patients. Conclusion The reverse sural fasciocutaneous flap with a cutaneous pedicle is a quick, versatile, easy and safe soft tissue defect coverage technique to cover most of the soft tissue defects of the lower limb in common orthopaedic practice and does not require any microvascular repair, though it may be cosmetically unappealing in a few cases. Level of evidence IV (Case series)

Estradiol 17β (E2β) and ascorbic acid (AA) have been implicated in cancer progression. However, little is known about the actions of biologically active metabolites of E2β, 2-hydroxyestradiol (2OHE2), 4-hydroxyestradiol (4OHE2), 2-methoxyestradiol (2ME2), and 4-methoxyestradiol (4ME2) synthesized sequentially by cytochrome P450, family 1, subfamily A (CYP1A1) and B (CYP1B1), polypeptide 1, and catechol-O-methyltransferase (COMT) on ovarian cancer. Herein, we examined the expression of CYP1A1, CYP1B1, COMT, and estrogen receptor α (ERα) and β (ERβ) in human ovarian surface epithelial (IOSE-385) and cancer cell lines (OVCAR-3, SKOV-3, and OVCA-432). We also investigated the roles of E2β, 2OHE2, 4OHE2, 2ME2, and 4ME2 in cell proliferation, and their interactive effects with AA on ovarian cells. We found the expression of CYP1A1, CYP1B1, COMT, ERα, and ERβ in most cell lines tested. Treating cells with physiological concentrations of E2β and its metabolites promoted (13%-42% of the control) IOSE-385 and OVCAR-3 proliferation. The ER blockade inhibited IOSE-385 (∼76%) and OVCAR-3 (∼87%) proliferative response to E2β but not to its metabolites. The ERα blockade inhibited (∼85%) E2β-stimulated OVCAR-3 proliferation, whereas ERβ blockade attenuated (∼83%) E2β-stimulated IOSE-385 proliferation. The AA at ≥250 μmol/L completely inhibited serum-stimulated cell proliferation in all cell lines tested; however, such inhibition in IOSE-385, OVCAR-3, and OVCA-432 was partially (∼10%-20%) countered by E2β and its metabolites. Thus, our findings indicate that E2β and its metabolites promote cell proliferation and antagonize the AA-suppressed cell proliferation in a subset of ovarian cancer cells, suggesting that blocking the actions of E2β and its metabolites may enhance AA’s antiovarian cancer activity.

Aerobic glycolysis is an important metabolic adaptation in tumors. However, there is mounting evidence that oxidative phosphorylation (OXPHOS) also contributes to metabolism in cancer cells. Therefore, agents targeting OXPHOS can serve as novel anticancer agents. We will present data on small molecule agents that inhibit the proliferation of ovarian and other cancer cells by inhibiting mitochondrial electron transport. We have focused our attention on citral, plumbagin, curcumin, cinnamaldehyde, piperlongumine, perillaldehyde, nonenal and other naturally occurring agents. All of these molecules share a common molecular epitope, the unsaturated carbonyl that participates in redox reactions. Cancer cells treated with these agents show a marked decrease in oxygen consumption rate and an increase in extracellular acidification. The redox ratio (NADH/FAD) and cellular ATP levels also decrease in response to these small molecule agents. In our search for additional and more potent OXPHOS inhibitors we have discovered that the FDA-approved anti-malarial drug atovaquone is an efficient inhibitor of electron transport in ovarian cancer cells. Chronic administration of atovaquone decreases the growth of ID8 tumors in C57BL/6 mice. Investigation in to the mechanism of action of the unsaturated carbonyl compounds indicates that their initial effect in cancer cells is the immediate and substantial rise in oxygen radicals as a result of OXPHOS inhibition. This increase in reactive oxygen causes extensive oxidative damage leading to DNA strand breaks. Subsequently, we have observed activation of p53-mediated apoptosis. These experiments are suggesting that inhibition of OXPHOS and the subsequent increase in intracellular oxygen radicals can result in the reactivation of the tumor suppressive responses of at least a subset of the p53 mutants. Additionally, our studies also indicate that the oxidative stress occurring as a result of OXPHOS inhibition directly leads to inhibition of ion transport through the Na+/K+-ATPase. As a result of this inhibition, cancer cells are unable to maintain a normal membrane potential. Studies are currently underway to determine if the inability to maintain membrane potential also contributes to apoptotic cancer cell death induced by these unsaturated carbonyl-containing compounds. Oxidative stress caused by these compounds leads to an increase in superoxide dismutase, catalase and glutathione synthesis via the activation of Nrf-2. Inhibition of Nrf-2 results in an increase in the potency of the unsaturated carbonyl compounds. We are therefore examining Nrf-2 increase as a form of chemoresistance mechanism that likely impinges on the anti-cancer activity of the unsaturated carbonyl compounds. These studies are allowing us to develop medicinal chemistry-based approaches to develop novel molecules with increased potency and targetability as OXPHOS inhibitors for the treatment of ovarian cancer. Citation Format: Arvinder Kapur, Amruta Nayak, Mildred Felder, Allegra Cappucini, Spencer Ericksen, Yousef Alharbi, Bikash Pattnaik, Lisa Barroilhet, and Manish S. Patankar. TARGETING OVARIAN TUMORS WITH OXPHOS INHIBITORS [abstract]. In: Proceedings of the 12th Biennial Ovarian Cancer Research Symposium; Sep 13-15, 2018; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2019;25(22 Suppl):Abstract nr NT-103.

PURPOSE: Significant remodeling of the extracellular matrix (ECM) occurs in human ovarian cancer and has been observed in both high grade and low grade tumors as well as ovaries from high risk patients with BRCA mutations. Uniquely quantifying alterations in the tumor microenvironment (TME) could be used as a new diagnostic tool, e.g. to complement histology; provide insight into disease etiology; and assess treatment efficacy through minimally invasive in vivo imaging. Current clinical modalities (CT, MRI, PET) lack the resolution for this purpose. Our efforts have focused on examining collagen alterations across a spectrum of human ovarian tumors, where the changes can serve as quantitative biomarkers. Alterations can be reflected in increased collagen concentration, changes in alignment of collagen molecules within fibrils and/or fibers and/or up-regulation of different collagen isoforms, e.g. Col III. METHODS AND RESULTS: We used the collagen specific/sensitive Second Harmonic Generation (SHG) imaging microscopy to probe collagen architecture over size scales that range from the macromolecular structural properties to fibril/fiber morphology. First, we used SHG polarization analyses to probe collagen macromolecular/supramolecular properties to discriminate ex vivo human tissues (normal stroma, benign tumors, and high grade serous tumors) by determination of: i) collagen alpha helical pitch angle, ii) alignment of collagen molecules within fibrils, and iii) collagen helical chirality via SHG circular dichroism (SHG-CD). The largest differences were between normal stroma and benign tumors, consistent with gene expression data showing Col III is up-regulated in the latter. The different tissues also displayed differing collagen alignment within fibrils and SHG-CD responses, consistent with either Col III incorporation or randomization of Col I alignment within benign and high-grade tumors fibrils. These results collectively indicate the fibril assemblies are distinct in all tissues and likely result from synthesis of new collagen rather than remodeling of existing collagen. Importantly, these techniques do not require exogenous labels, and additionally, provide sub-resolution structural information previously obtained through ultrastructural analysis that cannot be performed on intact tissues. We next implemented a novel form of 3D texture analysis and machine learning to delineate the fibrillar morphology observed in SHG images of normal stroma, high risk stroma, benign tumors, and a spectrum of malignant tumors (high grade serous, low grade serous, and endometrioid). We extracted textural features in the 3D image sets to build statistical models of each class and we achieved clinically significant 83-91% classification accuracies for the six classes. Importantly, the 3D analysis significantly outperformed our prior 2D methods. This classification based on collagen morphology will complement conventional classification based on genetic profiles and can serve as an additional biomarker. CONCLUSIONS: Taken together, the combination of the macro/supramolecular probes and the fiber morphology classification will greatly increase our understanding of the TME evolution in human ovarian cancer. These methods and their findings have clinical translational significance in terms of understanding disease etiology, and also by enhancing prognostic and diagnostic capabilities. Citation Format: Kirby R. Campbell, Rajeev Chaudhary, Julia Handel, Bruce Wen, Vikas Singh, Manish Patankar and Paul J. Campagnola. COLLAGEN ALTERATIONS IN HUMAN OVARIAN CANCER PROBED BY SECOND HARMONIC GENERATION (SHG) IMAGING MICROSCOPY [abstract]. In: Proceedings of the 12th Biennial Ovarian Cancer Research Symposium; Sep 13-15, 2018; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2019;25(22 Suppl):Abstract nr AP19.

Ovarian cancer is the fifth most common cause of cancer-related deaths in women in the United States. Most women with ovarian cancer present with advanced disease. Even though initial response to surgery and chemotherapy is generally positive, many patients relapse with chemoresistant disease. We are especially interested in finding natural products that have anti-neoplastic activity against relapsed disease. Here, we report fabclavine, a secondary metabolite from Xenorhabdus budapestensis as novel anti-cancer agent. Fabclavine was isolated and purified from cell-free supernatants of Xbu cultures. In a two-step procedure, active compounds were first precipitated from the supernatant with acetone and subsequently purified via reverse phase chromatography. Proliferation assays conducted on several ovarian cancer cell lines such as OVCAR3, OVCA433, ID8, IOSE, show that fabclavine inhibits the cancer cell proliferation at nanomolar (250-400 nM) concentration but has no effect on IOSE at that concentration. The ovarian cancer cell line OVCA33 when tested in proliferation assay showed, they are sensitive to fabclavine at a ten-fold lower concentration than cisplatin. Besides proliferation assay in 2D culture, we also tested the effect of fabclavine in 3D culture of ovarian cancer cell lines. The results indicate, fabclavine was equally effective in 3D culture and killed 40-50% of the cells in spheroids. In addition, fabclavine was also tested against cancer stem cells isolated from ovarian cancer patient and grown in 3D culture and it inhibited the growth of stem cells by 45%. Treatment of ovarian cancer cell lines with Fabclavine indicated DNA damage and an increase in cleaved caspase 3 and Annexin V binding, confirming that this agent was killing the OVCAR3, ID8 and OVCA433 cancer cell lines via apoptosis. Further experiments are underway to determine the apoptosis pathway (intrinsic or extrinsic) activated by fabclavine. Here we are describing for the first time a novel agent which is water soluble, active at low concentration and conveniently purified from cell free supernatant of bacterial culture. These properties of fabclavine makes it an excellent molecule to develop as therapy against ovarian tumors. Citation Format: Arvinder K Kapur, Mayur Kajla, Susan Paskewitz, Pooja Mehta, Geeta Mehta, Manish S Patankar. FABCLAVINE, A SECONDARY METABOLITE FROM XENORHABDUS BUDAPESTENSIS AS THERAPY AGAINST OVARIAN CANCER [abstract]. In: Proceedings of the 12th Biennial Ovarian Cancer Research Symposium; Sep 13-15, 2018; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2019;25(22 Suppl):Abstract nr NT-096.

Ovarian cancer remains one of the leading causes of cancer-related deaths in women worldwide, with an estimated 295,414 new cases and 184,799 deaths to occur in 2018. In the United States, although this malignancy is not in the top 10 for number of estimated new cases, it is the 5th leading cause of cancer-related deaths in women. This disparity is due to the fact that most ovarian cancers are not diagnosed until late stages when only limited options for treatment are available. Therefore, it is important to uncover novel molecular mechanisms that can be targeted to control this deadly cancer. The polo-like kinases (PLKs 1-5) are a family of serine/threonine kinases that that primarily play key roles in cell cycle progression, and have been linked to cancer pathogenesis. Limited information is available regarding the role of PLK5 in cancer. PLK5 is structurally unique, in that it has been shown to be missing the majority of the kinase domain that the other family members have. Interestingly, although PLK5 is not expressed in many tissues, it has been found to be present in appreciable levels in fallopian tube tissue, which suggests that PLK5 may be important in fallopian tube biology. Contrary to previous dogma, recent research has suggested that most ovarian cancers may actually have their origin in the fallopian tubes. Keeping this in mind, we wanted to explore the role of PLK5 in fallopian cancer. To this end, we performed a quantitative immunostaining of PLK5 in a fallopian tube disease tissue microarray (TMA) containing 5 normal tissues, 10 cases of inflammation, 10 fallopian adenocarcinoma, and 4 adjacent normal tissues. Following staining, the TMA was scanned with the Vectra platform and immunostaining was analyzed using InForm software that allows us to quantitatively measure the PLK5 intensity in each tissue and subcellular compartment. Our data demonstrated that PLK5 protein levels were significantly decreased in fallopian tumors compared to normal fallopian tissue (p = 0.01). Interestingly, although there was no significant difference between inflamed tissue and normal tissue, PLK5 levels were significantly reduced in the fallopian tube adenocarcinomas compared to the inflamed fallopian tissue (p Citation Format: Mary A. Ndiaye, Shengqin Su, Rebecca M. Baus, Wei Huang, Manish S. Patankar, Nihal Ahmad. Potential tumor suppressor function of polo-like kinase 5 in ovarian cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1251.

Plumbagin and atovaquone are chemotoxic to ovarian, breast and other tumors. Both molecules inhibit oxidative phosphorylation causing a rapid increase in intracellular oxygen radicals and apoptosis. Oxidative stress is also known to inhibit the activity of Na+/K+-ATPase (NKA), the ion channel that maintains the membrane potential. Here, we investigate if the oxidative stress mediated by plumbagin and atovaquone also leads to inhibition of NKA activity. We confirm that plumbagin and atovaquone inhibit proliferation of three human (OVCAR-3, SKOV-3 and TYKNu) and one mouse (ID8) ovarian cancer cell lines. Using SKOV-3 and OVCAR-3 as models for ovarian cancer, we demonstrate that oxygen radical scavenger, N-acetylcysteine (NAC) attenuated the cytotoxicity of plumbagin and atovaquone. Using whole cell patch clamping we demonstrate that plumbagin and atovaquone inhibit outward and inward current flowing through NKA in SKOV-3 and OVCAR-3. Both drugs decrease cellular ATP. Providing exogenous ATP (5 mM) in the pipet solution used during patch clamping did not recover NKA activity in the plumbagin or atovaquone treated SKOV-3 and OVCAR-3 cells. However, pretreatment of the cells with NAC completely abrogated the NKA inhibitory activity of plumbagin and atovaquone. Exposure of the SKOV-3 cells to either of the drugs for 1-2 h resulted in a significant decrease in the expression of NKA. We conclude that oxidative stress caused by plumbagin and atovaquone degrades NKA and hence the membrane potential cannot be optimally maintained. Evaluation of compounds that induce oxidative stress should therefore consider contribution of NKA inhibition to the cytotoxic activity of such agents. Citation Format: Yousef Alharbi, Arvinder Kapur, Mildred Felder, Lisa Barroilhet, Bikash Pattnaik, Manish S. Patankar. Plumbagin and atovaquone inhibit Na+/K+-ATPase through the generation of oxidative stress [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 891.

This paper studies pricing derivatives in an age-dependent semi-Markov modulated market. We consider a financial market where the asset price dynamics follow a regime switching geometric Brownian motion model in which the coefficients depend on finitely many age-dependent semi-Markov processes. We further allow the volatility coefficient to depend on time explicitly. Under these market assumptions, we study locally risk minimizing pricing of a class of European options. It is shown that the price function can be obtained by solving a non-local B-S-M type PDE. We establish existence and uniqueness of a classical solution of the Cauchy problem. We also find another characterization of price function via a system of Volterra integral equation of second kind. This alternative representation leads to computationally efficient methods for finding price and hedging. Finally, we analyze the PDE to establish continuous dependence of the solution on the instantaneous transition rates of semi-Markov processes. An explicit expression of quadratic residual risk is also obtained., 24 pages

Remodeling of the collagen architecture in the extracellular matrix (ECM) has been implicated in ovarian cancer. To quantify these alterations we implemented a form of 3D texture analysis to delineate the fibrillar morphology observed in 3D Second Harmonic Generation (SHG) microscopy image data of normal (1) and high risk (2) ovarian stroma, benign ovarian tumors (3), low grade (4) and high grade (5) serous tumors, and endometrioid tumors (6). We developed a tailored set of 3D filters which extract textural features in the 3D image sets to build (or learn) statistical models of each tissue class. By applying k-nearest neighbor classification using these learned models, we achieved 83–91% accuracies for the six classes. The 3D method outperformed the analogous 2D classification on the same tissues, where we suggest this is due the increased information content. This classification based on ECM structural changes will complement conventional classification based on genetic profiles and can serve as an additional biomarker. Moreover, the texture analysis algorithm is quite general, as it does not rely on single morphological metrics such as fiber alignment, length, and width but their combined convolution with a customizable basis set.

Detection, abstraction and segmentation of the retinal macula is of utmost prominence while studying the effects of macular degeneration. The algorithm deployed uses two steps to pin-point the exact location of the macula. We tested the algorithm on the retinal fundus images acquired from the subsection of MESSIDOR database. Usage of the digital image processing techniques expedite the better extraction of the desired regions. To establish the results, we computed the accuracy, sensitivity and specificity of our outcomes with that of the ground truth images. To segment the macula is our main ambition in high quality fundus images. We provide a novel approach of automated seeding region growing technique which has rarely been used previously. Our algorithm displays great latency in segmenting the large database of affected retinas.

Within last 10 years, much amount of research is dedicated to the field of neural sciences, image processing and computer vision regarding the significant issues related to face recognition techniques in machine learning algorithms. From many different theories and explanations for face recognition, which predominantly show that the survey and standardizing of these algorithms is itself a difficult task. The aim of this research is to recognize the out of plane non-frontal faces. In this paper, we used the PCA Eigen-face method for the face recognition with the help of Scale Invariant Features Transform procedure over the corner points to transform pose variant faces into virtual frontal faces.

Diabetic Retinopathy is an abnormality of eye in which the retina of patient is affected due to an increasing amount of insulin in blood. The symptoms can distort or blur the patient's vision and thus lead blindness. For automatic detection of exudates we first have to differentiate intensity levels of exudate and non-exudate pixels. Matched filter is used for same. Tuning of matched filter is an important criteria which is presented in this paper. This paper contains how to tune and modify matched filter response for easily segmentation of Hard Exudates. It also contains graphical experimented results for different values of sigma and how accuracy of the algorithm varies with it. Experimentation gives 99.62% accuracy of classification of exudate — non-exudate pixels and subject level accuracy is found to be 93.75% in identifying the abnormal (with exudates) and normal (without exudates) images respectively.

Steel plates are frequently used as structural element in various industries and structures such as bridges, buildings, Metal plates etc. Structural failure may result in a major societal collapse and economical meltdown. Thus to avoid such financial breakdown it is necessary to examine plate structure and its harmonics. In protection of structures it is extremely important to measure the vibration and its harmonic analysis. Harmonics are measured in terms of vibrations of an artefact. Therefore measurement of natural frequency by analysing vibrations is essential. Natural frequency then can be used to calculate different characteristics of a material such as modulus of elasticity and Stiffness. Modulus of Elasticity of a material is its ability to return to its normal shape, whereas Stiffness of a material is a rigidity of an object. Hence, these properties of a steel plate are used to make a well-balanced structure. This paper represents harmonic analysis and its different features of steel plate by free ball impact testing set up. The vibration induced due to impact are sensed using piezoelectric type accelerometer. The spectral analysis of captured vibration signal is performed using MATLAB software and attributes of plates are calculated. It is observed that modulus of elasticity, Stiffness and fundamental frequency remains nearly same under various impact energy.

The monoterpenoid, citral, when delivered through PEG-b-PCL nanoparticles inhibits in vivo growth of 4T1 breast tumors. Here, we show that citral inhibits proliferation of multiple human cancer cell lines. In p53 expressing ECC-1 and OVCAR-3 but not in p53-deficient SKOV-3 cells, citral induces G1/S cell cycle arrest and apoptosis as determined by Annexin V staining and increased cleaved caspase3 and Bax and decreased Bcl-2. In SKOV-3 cells, citral induces the ER stress markers CHOP, GADD45, EDEM, ATF4, Hsp90, ATG5 and phospho-eIF2α. The molecular chaperone 4-phenylbutyric acid attenuates citral activity in SKOV-3 but not in ECC-1 and OVCAR-3 cells. In p53-expressing cells, citral increases phosphorylation of serine-15 of p53. Activation of p53 increases Bax, PUMA and NOXA expression. Inhibition of p53 by pifithrin-α, attenuates citral-mediated apoptosis. Citral increases intracellular oxygen radicals and this leads to activation of p53. Inhibition of glutathione synthesis by L-buthionine sulfoxamine increases potency of citral. Pretreatment with N-acetylcysteine decreases phosphorylation of p53 in citral-treated ECC-1 and OVCAR-3. These results define a p53-dependent and in the absence of p53, ER stress-dependent mode of action of citral. This study indicates that citral in PEG-b-PCL nanoparticle formulation should be considered for treatment of breast and other tumors.

Presacral bleeding is a dreaded complication of pelvic surgery. Rapid and effective control of such bleeding is important to avoid potentially life-threatening outcomes. Various methods for controlling presacral bleeding, all with only limited success, have been described in the literature. We report the alternative technique of using the argon beam coagulator (ABC) to control presacral bleeding. We demonstrate its efficacious use in both open surgery and a laparoscopic case. Our approach involved applying an argon beam at bone setting directly to the bleeders and using a "point and shoot" technique. We found that ABC is a simpler, equally effective and expeditious way of addressing presacral bleeding. To the best of our knowledge, there has been only one previously reported case in the literature of the use of ABC to control presacral bleeding.