Search results for: tumor evolution

Authors: Donna L. Roberts

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Heroin has appeared on the drug scene before. Yet the current opioid crisis differs in significant ways. In order to address the grave challenges, this epidemic poses, the unique precipitating and sustaining conditions must be thoroughly examined. This research explored the various aspects of the political, economic, and social conditions that created a 'perfect storm' for the evolution and maintenance of the current opioid crisis. Specifically, the epidemiology, demographics, and progression of addiction inherent in the current crisis were compared to the patterns of past opioid use. Additionally, the role of pharmaceutical companies and prescribing physicians, the nature and pharmaceutical properties of the available substances and the changing socioeconomic climate were considered. Results indicated that the current crisis differs significantly with respect to its evolution, magnitude, prevalence, and widespread societal effects. Precipitated by a proliferation of prescription medication and sustained by the availability of cheaper, more potent street drugs, including new versions of synthetic opioids, the current crisis presents unprecedented challenges affecting a wider and more diverse segment of society. The unique aspects of this epidemic demand unique approaches to addressing the problem. Understanding these differences is a key step in working toward a practical and enduring solution.

Keywords: addiction, drug abuse, opioids, opioid crisis

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Authors: Selma Sbit, Mohamed Bechir Dadi, Belgacem Chibani Rhaimi

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Incorporating Home eNodeB (HeNB) in cellular networks, e.g. Long Term Evolution Advanced (LTE-A), is beneficial for extending coverage and enhancing capacity at low price especially within the non-line-of sight (NLOS) environments such as homes. HeNB or femtocell is a small low powered base station which provides radio coverage to the mobile users in an indoor environment. This deployment results in a heterogeneous network where the available spectrum becomes shared between two layers. Therefore, a problem of Inter Cell Interference (ICI) appears. This issue is the main challenge in LTE-A. To deal with this challenge, various techniques based on frequency, time and power control are proposed. This paper deals with the impact of carrier aggregation and higher order MIMO (Multiple Input Multiple Output) schemes on the LTE-Advanced performance. Simulation results show the advantages of these schemes on the system capacity (4.10⁹ b/s/Hz when bandwidth B=100 MHz and when applying MIMO 8x8 for SINR=30 dB), maximum theoretical peak data rate (more than 4 Gbps for B=100 MHz and when MIMO 8x8 is used) and spectral efficiency (15 b/s/Hz and 30b/s/Hz when MIMO 4x4 and MIMO 8x8 are applying respectively for SINR=30 dB).

Keywords: capacity, carrier aggregation, LTE-Advanced, MIMO (Multiple Input Multiple Output), peak data rate, spectral efficiency

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Authors: Ghada Esheba, Ebtisam Aljerayan, Afnan Al-Ghamdi, Atheer Alsharif, Hanan alzahrani

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Background: Primary ovarian neoplasms comprise a heterogeneous group of tumors of three main subtypes: surface epithelial, germ cell, and sex cord-stromal. The wide morphological variation within and between these groups can result in diagnostic difficulties. Gonadal sex cord-stromal tumors (SCST) represent one of the most heterogeneous categories of human neoplasms, because they may contain various combinations of different gonadal sex cord and stromal element. Aim: The aim of this work is to highlight the clinicopathological characteristics of SCST and to assess the value of alpha-inhibin and calretinin in the distinction between SCST and their mimics. Material and methods: This study was carried out on 100 cases using full tissue sections; 70 cases were SCST and 30 cases were histological mimics of SCST. The cases were studied using immunohistochemically using alpha-inhibin. In addition, an ovarian tissue microarray containing 170 benign and malignant ovarian neoplasms was also studied immunohistochemically for calretinin expression. The ovarian microarray included 14 SCST, 59 ovarian serous borderline tumors, 17 mucinous borderline tumors, 10 mucinous adenocarcinomas, 32 endometrioid adenocarcinomas, 34 clear cell carcinomas, and 4 germ cell tumors. Results: 99% of SCST examined using full tissue sections exhibited positive cytoplasmic staining for inhibin. On the contrary, only 7% of the histological mimics (P value < 0.0001). 86% of SCST in the tissue microarray were positive for calretinin with nuclear and/or cytoplasmic staining compared to only 7% of the other tumor types (P value < 0.0001). Conclusions: SCST have characteristic clinicopathological and immunohistochemical features and their recognition is crucial for proper diagnosis and treatment. Alpha-inhibin and calretinin are of great help in the diagnosis of sex cord-stromal tumors.

Keywords: calretinin, granulosa cell tumor, inhibin, sex cord-stromal tumors

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Authors: Hadjadj Abdechafik, Kious Mecheri, Ameur Aissa

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The objective of this study is to develop a process of treatment of the vibratory signals generated during a horizontal high speed milling process without applying any coolant in order to establish a monitoring system able to improve the machining performance. Thus, many tests were carried out on the horizontal high speed centre (PCI Météor 10), in given cutting conditions, by using a milling cutter with only one insert and measured its frontal wear from its new state that is considered as a reference state until a worn state that is considered as unsuitable for the tool to be used. The results obtained show that the first harmonic follow well the evolution of frontal wear, on another hand a wavelet transform is used for signal processing and is found to be useful for observing the evolution of the wavelet approximations through the cutting tool life. The power and the Root Mean Square (RMS) values of the wavelet transformed signal gave the best results and can be used for tool wear estimation. All this features can constitute the suitable indicators for an effective detection of tool wear and then used for the input parameters of an online monitoring system. Although we noted the remarkable influence of the machining cycle on the quality of measurements by the introduction of a bias on the signal, this phenomenon appears in particular in horizontal milling and in the majority of studies is ignored.

Keywords: flank wear, vibration, milling, signal processing, monitoring

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Authors: Bruno D. Souza, Gerson G. Cunha, Michael O. Ferreira, Roberto Rosenhaim, Robson C. Santos, Sergio O. Santos

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Devices and applications that use satellite-based positioning are becoming more popular day-by-day. Thus, evolution and improvement in this technology are mandatory. Accordingly, satellite georeferenced systems need to accomplish the same evolution rhythm. Either GPS (Global Positioning System) or its similar Russian GLONASS (Global Navigation Satellite System) are system samples that offer us powerful tools to plot coordinates on the earth surface. The development of this research aims the study of several aspects related to use of GPS and GLONASS technologies, given its application and collected data improvement during geodetic data acquisition. So, both relevant theoretic and practical aspects are considered. In this context, at the theoretical part, the main systems' characteristics are shown, observing its similarities and differences. At the practical part, a series of experiences are performed and obtained data packages are compared in order to demonstrate equivalence or differences among them. The evaluation methodology targets both quantitative and qualitative analysis provided by GPS and GPS/GLONASS receptors. Meanwhile, a specific collected data storage system was developed to better compare and analyze them (SisGeo - Georeferenced Research Comparison Support System).

Keywords: satellites, systems, applications, experiments, receivers

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Authors: Warda Jabeen, Romaisa Shamim Khan, Osama Shakeel, Ahmed Faraz Bhatti, Raza Hussain

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Background: The worldwide incidence of cutaneous melanoma (CM) has been on the rise over the past few decades. Primary prevention and early treatment remain the focus of management to reduce the burden of disease. This entails identification of risk factors to prompt early diagnosis. In Pakistan, there is a scarcity of clinico-pathological data relating to cutaneous malignant melanoma. Objective: The purpose of this study was to analyze the epidemiological and clinical characteristics of patients presenting with cutaneous malignant melanoma in Pakistan, and to compare the results with other studies. Method: Shaukat Khanum Memorial Cancer Hospital and Research Centre is currently the only dedicated cancer hospital in the country, accepting patients from all over Pakistan. Majority of the patients, however, belong to the northern half of the country. From the recorded data of the hospital, all cutaneous melanoma cases were identified and evaluated. Results: Between 1997 and 2017, a total of 169 cutaneous melanoma patients were registered at Shaukat Khanum. Mean age was 47.5 years. The highest incidence of melanoma was seen in the age group 40-59 years (n=69, 40.8%). Most commonly reported clinical subtype was unspecified melanoma (n=154, 91%). Amongst those in which T stage was reported, the most frequently observed T-stage at presentation was T4 (n=23, 13.6%). With regards to body distribution, in our study CM was seen most commonly in the lower limb including the hip. The yearly incidence of melanoma has increased/remained stable from 2007 to 2017. Conclusion: cutaneous malignant melanoma is a fairly common disease in Pakistan. Patients tend to present at a more advanced stage as compared to patients in developed countries. Identification of risk factors and tumor characteristics is therefore of paramount importance to deal with these patients.

Keywords: epidemiology of cutaneous malignant melanoma, cutaneous malignant melanoma, Pakistan, skin cancer

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Authors: Swati Sharma, R. P. Sharma

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We intend to study the nonlinear evolution of the parallel propagating finite frequency Alfvén wave (also called Dispersive Alfvén wave/Hall MHD wave) propagating in the solar wind regime of the solar region when a perpendicularly propagating magnetosonic wave is present in the background. The finite frequency Alfvén wave behaves differently from the usual non-dispersive behavior of the Alfvén wave. To study the nonlinear processes (such as filamentation) taking place in the solar regions such as solar wind, the dynamical equation of both the waves are derived. Numerical simulation involving finite difference method for the time domain and pseudo spectral method for the spatial domain is then performed to analyze the transient evolution of these waves. The power spectra of the Dispersive Alfvén wave is also investigated. The power spectra shows the distribution of the magnetic field intensity of the Dispersive Alfvén wave over different wave numbers. For DAW the spectra shows a steepening for scales larger than the proton inertial length. This means that the wave energy gets transferred to the solar wind particles as the wave reaches higher wave numbers. This steepening of the power spectra can be explained on account of the finite frequency of the Alfvén wave. The obtained results are consistent with the observations made by CLUSTER spacecraft.

Keywords: solar wind, turbulence, dispersive alfven wave

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Authors: Priyanka Agrawal, Janou Koskamp, Amir Raoof, Mariette Wolthers

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Calcite is the main mineral found in carbonate rocks, which form significant hydrocarbon reservoirs and subsurface repositories for CO2 sequestration. The injected CO2 mixes with the reservoir fluid and disturbs the geochemical equilibrium, triggering calcite dissolution. Different combinations of fluid chemistry and injection rate may therefore result in different evolution of porosity, permeability and dissolution patterns. To model the changes in porosity and permeability Kozeny-Carman equation K∝〖(∅)〗^n is used, where K is permeability and ∅ is porosity. The value of n is mostly based on experimental data or pore network models. In pore network models, this derivation is based on accuracy of relation used for conductivity and pore volume change. In fact, at a single pore scale, this relationship is the result of the pore shape development due to dissolution. We have prepared a new reactive transport model for a single pore which simulates the complex chemical reaction of carbonic-acid induced calcite dissolution and subsequent pore-geometry evolution at a single pore scale. We use COMSOL Multiphysics package 5.3 for the simulation. COMSOL utilizes the arbitary-Lagrangian Eulerian (ALE) method for the free-moving domain boundary. We examined the effect of flow rate on the evolution of single pore shape profiles due to calcite dissolution. We used three flow rates to cover diffusion dominated and advection-dominated transport regimes. The fluid in diffusion dominated flow (Pe number 0.037 and 0.37) becomes less reactive along the pore length and thus produced non-uniform pore shapes. However, for the advection-dominated flow (Pe number 3.75), the fast velocity of the fluid keeps the fluid relatively more reactive towards the end of the pore length, thus yielding uniform pore shape. Different pore shapes in terms of inlet opening vs overall pore opening will have an impact on the relation between changing volumes and conductivity. We have related the shape of pore with the Pe number which controls the transport regimes. For every Pe number, we have derived the relation between conductivity and porosity. These relations will be used in the pore network model to get the porosity and permeability variation.

Keywords: single pore, reactive transport, calcite system, moving boundary

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Authors: James V. Luisi

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Understanding consciousness requires a synthesis of ideas from multiple disciplines, including obvious ones like psychology, biology, evolution, neurology, and neuroscience, as well as less obvious ones like protozoology, botany, entomology, carcinology, herpetology, mammalogy, and computer sciences. Furthermore, to incorporate the necessary backdrop, it is best presented in a theme of Eastern philosophy, specifically leveraging the teachings of Buddhism for its relevance to early thought on consciousness. These ideas are presented as a multi-level framework that illustrates the various aspects of consciousness within a tapestry of foundational and dependent building blocks as to how living organisms evolved to understand elements of their reality sufficiently to survive, and in the case of Homo sapiens, eventually move beyond meeting the basic needs of survival, but to also achieve survival of the species beyond the eventual fate of our planet. This is not a complete system of thought, but just a framework of consciousness gathering some of the key elements regarding the evolution of consciousness and the advent of free will, and presenting them in a unique way that encourages readers to continue the dialog and thought process as an experience to enjoy long after reading the last page. Readers are encouraged to think for themselves about the issues raised herein and to question every facet presented, as much further exploration is needed. Needless to say, this subject will remain a rapidly evolving one for quite some time to come, and it is probably in the interests of everyone to at least consider attaining both an ability and willingness to participate in the dialog.

Keywords: consciousness, sentience, intelligence, artificial intelligence, Buddhism

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Authors: Walid Ibrahim, Abdul Kasem, Sudeendra Doddi, Ilaria Giono, Tareq Sabagh, Muhammad Ammar, Nermin Osman

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Background: wire-guided localization (WL) is the most widely used method for the localization of non-palpable breast lesions. SAVI SCOUT occult lesion localization (SSL) is a new technique in breast-conservative surgery. SSL has the potential benefit of improving radiology workflow as well as accurate localization. Purpose: The purpose of this study is to compare the breast tissue specimen volume and weight and margin excision between WL and SSL. Materials and methods: A single institution retrospective analysis of 377 female patients who underwent wide local breast excision with SAVI SCOUT and or wire-guided technique between 2018 and 2021 in a UK University teaching hospital. Breast department. Breast tissue specimen volume and weight, and margin excision have been evaluated in the three groups of different localization. Results: Three hundred and seventy-seven patients were studied. Of these, 261 had wire localization, 88 had SCOUT and 28 had dual localization techniques. Tumor size ranged from 1 to 75mm (Median 20mm). The pathology specimen weight ranged from 1 to 466gm (Median 46.8) and the volume ranged from 1.305 to 1560cm³ (Median 106.32 cm³). SCOUT localization was associated with a significantly low specimen weight than wire or the dual technique localization (Median 41gm vs 47.3gm and 47gm, p = 0.029). SCOUT was not associated with better specimen volume with a borderline significance in comparison to wire and combined techniques (Median 108cm³ vs 105cm³ and 105cm³, p = 0.047). There was a significant correlation between tumor size and pathology specimen weight in the three groups. SCOUT showed a better >2mm safety margin in comparison to the other 2 techniques (p = 0.031). Conclusion: Preoperative SCOUT localization is associated with better specimen weight and better specimen margin. SCOUT did not show any benefits in terms of specimen volume which may be due to difficulty in getting the accurate specimen volume due to the irregularity of the soft tissue specimen.

Keywords: scout, wire, localization, breast

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Authors: Phyo Wai Aung, Sysoev Oleg Evgenevich, Boris Necolavet Maryin

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The article deals with theoretical problems of correlation of processes of microstructure changes of structural materials under cyclic loading and acoustic emission. The ways of the evolution of a microstructure under the influence of cyclic loading are shown depending on the structure of the initial crystal structure of the material. The spectra of the frequency characteristics of acoustic emission signals are experimentally obtained when testing titanium samples for cyclic loads. Changes in the fractal dimension of the acoustic emission signals in the selected frequency bands during the evolution of the microstructure of structural materials from the action of cyclic loads, as well as in the destruction of samples, are studied. The experimental samples were made of VT-20 structural material widely used in aircraft and rocket engineering. The article shows the striving of structural materials for synergistic stability and reduction of the fractal dimension of acoustic emission signals, in accordance with the degradation of the microstructure, which occurs as a result of fatigue processes from the action of low cycle loads. As a result of the research, the frequency range of acoustic emission signals of 100-270 kHz is determined, in which the fractal dimension of the signals, it is possible to most reliably predict the durability of structural materials.

Keywords: cyclic loadings, material structure changing, acoustic emission, fractal dimension

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Authors: Piotr Podlipniak

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Social consolidation has often been indicated as an adaptive function of music which led to the evolution of music faculty. According to many scholars this function is possible thanks to musical rhythm that enables sensorimotor synchronization to a musical beat. The ability to synchronize to music allows performing music collectively which enhances social cohesion. However, the collective performance of music consists also in spectral synchronization that depends on musical pitch structure. Similarly to rhythmic synchronization, spectral synchronization is a result of ‘brain states alignment’ between people who collectively listen to or perform music. In order to successfully synchronize pitches performers have to adequately expect the pitch structure. The most common form of music which predominates among all human societies is tonal music. In fact tonality understood in the broadest sense as such an organization of musical pitches in which some pitch is more important than others is the only kind of musical pitch structure that has been observed in all currently known musical cultures. The perception of such a musical pitch structure elicits specific emotional reactions which are often described as tensions and relaxations. These facts provoke some important questions. What is the evolutionary reason that people use pitch structure as a form of vocal communication? Why different pitch structures elicit different emotional states independent of extra-musical context? It is proposed in the current presentation that in the course of evolution pitch structure became a human specific tool of communication the function of which is to induce emotional states such as uncertainty and cohesion. By the means of eliciting these emotions during collective music performance people are able to unconsciously give cues concerning social acceptance. This is probably one of the reasons why in all cultures people collectively perform tonal music. It is also suggested that tonal pitch structure had been invented socially before it became an evolutionary innovation of Homo sapiens. It means that a predisposition to tonally organize pitches evolved by the means of ‘Baldwin effect’ – a process in which natural selection transforms the learned response of an organism into the instinctive response. The hypothetical evolutionary scenario of the emergence of tonal pitch structure will be proposed. In this scenario social forces such as a need for closer cooperation play the crucial role.

Keywords: emotion, evolution, tonality, social consolidation

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Authors: Elena B. Cherepetskaya, Alexander A. Karabutov, Natalia B. Podymova, Ivan Sas

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Nonlinear evolution of broadband ultrasonic pulses passed through the rock specimens is studied using the apparatus ‘GEOSCAN-02M’. Ultrasonic pulses are excited by the pulses of Q-switched Nd:YAG laser with the time duration of 10 ns and with the energy of 260 mJ. This energy can be reduced to 20 mJ by some light filters. The laser beam radius did not exceed 5 mm. As a result of the absorption of the laser pulse in the special material – the optoacoustic generator–the pulses of longitudinal ultrasonic waves are excited with the time duration of 100 ns and with the maximum pressure amplitude of 10 MPa. The immersion technique is used to measure the parameters of these ultrasonic pulses passed through a specimen, the immersion liquid is distilled water. The reference pulse passed through the cell with water has the compression and the rarefaction phases. The amplitude of the rarefaction phase is five times lower than that of the compression phase. The spectral range of the reference pulse reaches 10 MHz. The cubic-shaped specimens of the Karelian gabbro are studied with the rib length 3 cm. The ultimate strength of the specimens by the uniaxial compression is (300±10) MPa. As the reference pulse passes through the area of the specimen without cracks the compression phase decreases and the rarefaction one increases due to diffraction and scattering of ultrasound, so the ratio of these phases becomes 2.3:1. After preloading some horizontal cracks appear in the specimens. Their location is found by one-sided scanning of the specimen using the backward mode detection of the ultrasonic pulses reflected from the structure defects. Using the computer processing of these signals the images are obtained of the cross-sections of the specimens with cracks. By the increase of the reference pulse amplitude from 0.1 MPa to 5 MPa the nonlinear transformation of the ultrasonic pulse passed through the specimen with horizontal cracks results in the decrease by 2.5 times of the amplitude of the rarefaction phase and in the increase of its duration by 2.1 times. By the increase of the reference pulse amplitude from 5 MPa to 10 MPa the time splitting of the phases is observed for the bipolar pulse passed through the specimen. The compression and rarefaction phases propagate with different velocities. These features of the powerful broadband ultrasonic pulses passed through the rock specimens can be described by the hysteresis model of Preisach-Mayergoyz and can be used for the location of cracks in the optically opaque materials.

Keywords: cracks, geological materials, nonlinear evolution of ultrasonic pulses, rock

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Authors: Lei Li, Ming M. Chai, Xiao X. Lu, Jia W. Wang

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The mixing process of two liquid layers in a cylindrical container includes the upper liquid with higher density rushing into the lower liquid with lighter density, the lower liquid rising into the upper liquid, meanwhile the two liquid layers having interactions with each other, forming vortices, spreading or dispersing in others, entraining or mixing with others. It is a complex process constituted of flow instability, turbulent mixing and other multiscale physical phenomena and having a fast evolution velocity. In order to explore the mechanism of the process and make further investigations, some experiments about the interfacial instability and mixing behavior between two liquid layers bounded in different volumes are carried out, applying the planar laser induced fluorescence (PLIF) and the high speed camera (HSC) techniques. According to the results, the evolution of interfacial instability between immiscible liquid develops faster than theoretical rate given by the Rayleigh-Taylor Instability (RTI) theory. It is reasonable to conjecture that some mechanisms except the RTI play key roles in the mixture process of two liquid layers. From the results, it is shown that the invading velocity of the upper liquid into the lower liquid does not depend on the upper liquid's volume (height). Comparing to the cases that the upper and lower containers are of identical diameter, in the case that the lower liquid volume increases to larger geometric space, the upper liquid spreads and expands into the lower liquid more quickly during the evolution of interfacial instability, indicating that the container wall has important influence on the mixing process. In the experiments of miscible liquid layers’ mixing, the diffusion time and pattern of the liquid interfacial mixing also does not depend on the upper liquid's volumes, and when the lower liquid volume increases to larger geometric space, the action of the bounded wall on the liquid falling and rising flow will decrease, and the liquid interfacial mixing effects will also attenuate. Therefore, it is also concluded that the volume weight of upper heavier liquid is not the reason of the fast interfacial instability evolution between the two liquid layers and the bounded wall action is limited to the unstable and mixing flow. The numerical simulations of the immiscible liquid layers’ interfacial instability flow using the VOF method show the typical flow pattern agree with the experiments. However the calculated instability development is much slower than the experimental measurement. The numerical simulation of the miscible liquids’ mixing, which applying Fick’s diffusion law to the components’ transport equation, shows a much faster mixing rate than the experiments on the liquids’ interface at the initial stage. It can be presumed that the interfacial tension plays an important role in the interfacial instability between the two liquid layers bounded in finite volume.

Keywords: interfacial instability and mixing, two liquid layers, Planar Laser Induced Fluorescence (PLIF), High Speed Camera (HSC), interfacial energy and tension, Cahn-Hilliard Navier-Stokes (CHNS) equations

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Authors: Woei-Shyan Lee, Yu-Liang Chuang

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The nano-mechanical properties of as-deposited Cu/Si thin films indented to a depth of 2000 nm are investigated using a nanoindentation technique. The nanoindented specimens are annealed at a temperature of either 160 °C or 210°C, respectively. The microstructures of the as-deposited and annealed samples are then examined via transmission electron microscopy (TEM). The results show that both the loading and the unloading regions of the load-displacement curve are smooth and continuous, which suggests that no debonding or cracking occurs during nanoindentation. In addition, the hardness and Young’s modulus of the Cu/Si thin films are found to vary with the nanoindentation depth, and have maximum values of 2.8 GPa and 143 GPa, respectively, at the maximum indentation depth of 2000 nm. The TEM observations show that the region of the Cu/Si film beneath the indenter undergoes a phase transformation during the indentation process. In the case of the as-deposited specimens, the indentation pressure induces a completely amorphous phase within the indentation zone. For the specimens annealed at a temperature of 160°C, the amorphous nature of the microstructure within the indented zone is maintained. However, for the specimens annealed at a higher temperature of 210°C, the indentation affected zone consists of a mixture of amorphous phase and nanocrystalline phase. Copper silicide (η-Cu3Si) precipitates are observed in all of the annealed specimens. The density of the η-Cu3Si precipitates is found to increase with an increasing annealing temperature.

Keywords: nanoindentation, Cu/Si thin films, microstructural evolution, annealing temperature

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Authors: Vincent Murray

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The glycopeptide bleomycin is used in the treatment of testicular cancer, Hodgkin's lymphoma, and squamous cell carcinoma. Bleomycin damages and cleaves DNA in human cells, and this is considered to be the main mode of action for bleomycin's anti-tumor activity. In particular, double-strand breaks are thought to be the main mechanism for the cellular toxicity of bleomycin. Using Illumina next-generation DNA sequencing techniques, the genome-wide sequence specificity of bleomycin-induced double-strand breaks was determined in human cells. The degree of bleomycin cleavage was also assessed at the transcription start sites (TSSs) of actively transcribed genes and compared with non-transcribed genes. It was observed that bleomycin preferentially cleaved at the TSSs of actively transcribed human genes. There was a correlation between the degree of this enhanced cleavage at TSSs and the level of transcriptional activity. Bleomycin cleavage is also affected by chromatin structure and at TSSs, the peaks of bleomycin cleavage were approximately 200 bp apart. This indicated that bleomycin was able to detect phased nucleosomes at the TSSs of actively transcribed human genes. The genome-wide cleavage pattern of the bleomycin analogues 6′-deoxy-BLM Z and zorbamycin was also investigated in human cells. As found for bleomycin, these bleomycin analogues also preferentially cleaved at the TSSs of actively transcribed human genes. The cytotoxicity (IC₅₀ values) of these bleomycin analogues was determined. It was found that the degree of enhanced cleavage at TSSs was inversely correlated with the IC₅₀ values of the bleomycin analogues. This suggested that the level of cleavage at the TSSs of actively transcribed human genes was important for the cytotoxicity of bleomycin and analogues. Hence this study provided a deeper understanding of the cellular processes involved in the cancer chemotherapeutic activity of bleomycin.

Keywords: anti-tumour activity, bleomycin analogues, chromatin structure, genome-wide study, Illumina DNA sequencing

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Authors: Aghaei Amirkhizi Navideh, Sadjadi Soodeh Sadat, Moghaddam Banaem Leila, Athari Allaf Mitra, Johari Daha Fariba

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Dendrimers are good candidates for preparing metal nanoparticles because they can structurally and chemically well-defined templates and robust stabilizers. Poly amidoamine (PAMAM) dendrimer-based multifunctional cancer therapeutic conjugates have been designed and synthesized in pharmaceutical industry. In addition, encapsulated nanoparticle surfaces are accessible to substrates so that catalytic reactions can be carried out. For preparation of dendimer-metal nanocomposite, a dendrimer solution containing an average of 55 Yb+3 ions per dendrimer was prepared. Prior to reduction, the pH of this solution was adjusted to 7.5 using NaOH. NaBH4 was used to reduce the dendrimer-encapsulated Yb+3 to the zerovalent metal. The pH of the resulting solution was then adjusted to 3, using HClO4, to decompose excess BH4-. The UV-Vis absorption spectra of the mixture were recorded to ensure the formation of Yb-G5-NH2 complex. High-resolution electron microscopy (HRTEM) and size distribution results provide additional information about dendimer-metal nanocomposite shape, size, and size distribution of the particles. The resulting mixture was irradiated in Tehran Research Reactor 2h and neutron fluxes were 3×1011 n/cm2.Sec and the specific activity was 7MBq. Radiochemical and chemical and radionuclide quality control testes were carried. Gamma Spectroscopy and High-performance Liquid Chromatography HPLC, Thin-Layer Chromatography TLC were recorded. The injection of resulting solution to solid tumor in mice shows that it could be resized the tumor. The studies about solid tumors and nano composites show that ytterbium encapsulated-dendrimer radiopharmaceutical could be introduced as a new therapeutic for the treatment of solid tumors.

Keywords: nano-radio pharmaceutical, ytterbium, PAMAM, dendrimers

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Authors: Hamid Mustafa, Adeela Ajmal, Kim EuiSoo, Noor-ul-Ain

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World wild, buffalo production is considered as most important component of food industry. Efficient buffalo production is related with reproductive performance of this species. Lack of knowledge of reproductive efficiency and its related genes in buffalo species is a major constraint for sustainable buffalo production. In this study, we performed some bioinformatics analysis on Follicle Stimulating Hormone Receptor (FSHR) gene and explored the possible relationship of this gene among different buffalo breeds and with other farm animals. We also found the evolution pattern for this gene among these species. We investigate CDS lengths, Stop codon variation, homology search, signal peptide, isoelectic point, tertiary structure, motifs and phylogenetic tree. The results of this study indicate 4 different motif in this gene, which are Activin-recp, GS motif, STYKc Protein kinase and transmembrane. The results also indicate that this gene has very close relationship with cattle, bison, sheep and goat. Multiple alignment (MA) showed high conservation of motif which indicates constancy of this gene during evolution. The results of this study can be used and applied for better understanding of this gene for better characterization of Follicle Stimulating Hormone Receptor (FSHR) gene structure in different farm animals, which would be helpful for efficient breeding plans for animal’s production.

Keywords: buffalo, FSHR gene, bioinformatics, production

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Authors: Navid Mosallaei, Mahmoud Reza Jaafari, Mohammad Yahya Hanafi-Bojd, Shiva Golmohammadzadeh, Bizhan Malaekeh-Nikouei

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Background: Docetaxel (DTX), a potent anticancer drug derived from the European yew tree, is effective against various human cancers by inhibiting microtubule depolymerization. Solid lipid nanoparticles (SLNs) have gained attention as drug carriers for enhancing drug effectiveness and safety. SLNs, submicron-sized lipid-based particles, can passively target tumors through the "enhanced permeability and retention" (EPR) effect, providing stability, drug protection, and controlled release while being biocompatible. Methods: The SLN formulation included biodegradable lipids (Compritol and Precirol), hydrogenated soy phosphatidylcholine (H-SPC) as a lipophilic co-surfactant, and Poloxamer 188 as a non-ionic polymeric stabilizer. Two SLN preparation techniques, probe sonication and microemulsion, were assessed. Characterization encompassed SLNs' morphology, particle size, zeta potential, matrix, and encapsulation efficacy. In-vitro cytotoxicity and cellular uptake studies were conducted using mouse colorectal (C-26) and human malignant melanoma (A-375) cell lines, comparing SLN-DTX with Taxotere®. In-vivo studies evaluated tumor inhibitory efficacy and survival in mice with colorectal (C-26) tumors, comparing SLNDTX withTaxotere®. Results: SLN-DTX demonstrated stability, with an average size of 180 nm and a low polydispersity index (PDI) of 0.2 and encapsulation efficacy of 98.0 ± 0.1%. Differential scanning calorimetry (DSC) suggested amorphous encapsulation of DTX within SLNs. In vitro studies revealed that SLN-DTX exhibited nearly equivalent cytotoxicity to Taxotere®, depending on concentration and exposure time. Cellular uptake studies demonstrated superior intracellular DTX accumulation with SLN-DTX. In a C-26 mouse model, SLN-DTX at 10 mg/kg outperformed Taxotere® at 10 and 20 mg/kg, with no significant differences in body weight changes and a remarkably high survival rate of 60%. Conclusion: This study concludes that SLN-DTX, prepared using the probe sonication, offers stability and enhanced therapeutic effects. It displayed almost same in vitro cytotoxicity to Taxotere® but showed superior cellular uptake. In a mouse model, SLN-DTX effectively inhibited tumor growth, with 10 mg/kg outperforming even 20 mg/kg of Taxotere®, without adverse body weight changes and with higher survival rates. This suggests that SLN-DTX has the potential to reduce adverse effects while maintaining or enhancing docetaxel's therapeutic profile, making it a promising drug delivery strategy suitable for industrialization.

Keywords: docetaxel, Taxotere®, solid lipid nanoparticles, enhanced permeability and retention effect, drug delivery, cancer chemotherapy, cytotoxicity, cellular uptake, tumor inhibition

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Authors: Maniyarasan Rajendran

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Every design has a process, and every architect deals in the ways best known to them. The design translation from the concept to completion change in accordance with their design philosophies, their tools, availability of resources, and at times the clients and the context of the design as well. The approach to understanding the design process requires formalisation of the design intents. The design process is characterised by change, with the time and the technology. The design flow is just indicative and never exhaustive. The knowledge and experience of stakeholders remain limited to the part they played in the project, and their ability to remember, and is through the Photographs. These artefacts, when circulated can hardly tell what the project is. They can never tell the narrative behind. In due course, the design processes are lost. The Design junctions are lost in the journey. Photographs acted as major source materials, along with its importance in architectural revivalism in the 19th century. From the history, we understand that it has been photographs, that act as the dominant source of evidence. The idea of recording is also followed with the idea of getting inspired from the records and documents. The design concept, the architectural firms’ philosophies, the materials used, the special needs, the numerous ‘Trial-and-error’ methods, design methodology, experience of failures and success levels, and the knowledge acquired, etc., and the various other aspects and methods go through in every project, and they deserve/ought to be recorded. The knowledge can be preserved and passed through generations, by documenting the design processes involved. This paper explores the idea of a process documentation as a tool of self-reflection, creation of architectural firm’ repository, and these implications proceed with the design evolution of the team.

Keywords: architecture, design, documentation, records

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Authors: Abdulbaset Saad, Adel Younis, Zuomin Dong

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For design optimization with high-dimensional expensive problems, an effective and efficient optimization methodology is desired. This work proposes a series of modification to the Differential Evolution (DE) algorithm for solving computation Intensive Black-Box Problems. The proposed methodology is called Radial Basis Meta-Model Algorithm Assisted Differential Evolutionary (RBF-DE), which is a global optimization algorithm based on the meta-modeling techniques. A meta-modeling assisted DE is proposed to solve computationally expensive optimization problems. The Radial Basis Function (RBF) model is used as a surrogate model to approximate the expensive objective function, while DE employs a mechanism to dynamically select the best performing combination of parameters such as differential rate, cross over probability, and population size. The proposed algorithm is tested on benchmark functions and real life practical applications and problems. The test results demonstrate that the proposed algorithm is promising and performs well compared to other optimization algorithms. The proposed algorithm is capable of converging to acceptable and good solutions in terms of accuracy, number of evaluations, and time needed to converge.

Keywords: differential evolution, engineering design, expensive computations, meta-modeling, radial basis function, optimization

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Authors: Carlos Tapia Cortez, Serkan Saydam, Jeff Coulton, Claude Sammut

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Strategic mineral commodities (SMC) both energetic and metals have long been fundamental for human beings. There is a strong and long-run relation between the mineral resources industry and society's evolution, with the provision of primary raw materials, becoming one of the most significant drivers of economic growth. Due to mineral resources’ relevance for the entire economy and society, an understanding of the SMC market behaviour to simulate price fluctuations has become crucial for governments and firms. For any human activity, SMC price fluctuations are affected by economic, geopolitical, environmental, technological and psychological issues, where cognition has a major role. Cognition is defined as the capacity to store information in memory, processing and decision making for problem-solving or human adaptation. Thus, it has a significant role in those systems that exhibit dynamic equilibrium through time, such as economic growth. Cognition allows not only understanding past behaviours and trends in SCM markets but also supports future expectations of demand/supply levels and prices, although speculations are unavoidable. Technological developments may also be defined as a cognitive system. Since the Industrial Revolution, technological developments have had a significant influence on SMC production costs and prices, likewise allowing co-integration between commodities and market locations. It suggests a close relation between structural breaks, technology and prices evolution. SCM prices forecasting have been commonly addressed by econometrics and Gaussian-probabilistic models. Econometrics models may incorporate the relationship between variables; however, they are statics that leads to an incomplete approach of prices evolution through time. Gaussian-probabilistic models may evolve through time; however, price fluctuations are addressed by the assumption of random behaviour and normal distribution which seems to be far from the real behaviour of both market and prices. Random fluctuation ignores the evolution of market events and the technical and temporal relation between variables, giving the illusion of controlled future events. Normal distribution underestimates price fluctuations by using restricted ranges, curtailing decisions making into a pre-established space. A proper understanding of SMC's price dynamics taking into account the historical-cognitive relation between economic, technological and psychological factors over time is fundamental in attempting to simulate prices. The aim of this paper is to discuss the SMC market cognition hypothesis and empirically demonstrate its dynamic-cognitive capacity. Three of the largest and traded SMC's: oil, copper and gold, will be assessed to examine the economic, technological and psychological cognition respectively.

Keywords: commodity price simulation, commodity price uncertainties, dynamic-cognition, dynamic systems

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Authors: Fatemeh Zeinali Sehrig

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Background: miRNAs play an important role in the post-transcriptional regulation of genes, including genes involved in DNA methylation (DNMTs), and are also important regulators of oncogenic pathways. The study of microRNAs and DNMTs in breast cancer allows the development of targeted treatments and early detection of this cancer. Methods and Materials: Clinical Patients and Samples: Institutional guidelines, including ethical approval and informed consent, were followed by the Ethics Committee (Ethics code: IR.IAU.TABRIZ.REC.1401.063) of Tabriz Azad University, Tabriz, Iran. In this study, tissues of 100 patients with breast cancer and tissues of 100 healthy women were collected from Noor Nejat Hospital in Tabriz. The basic characteristics of the patients with breast cancer included: 1)Tumor grade(Grade 3 = 5%, Grade 2 = 87.5%, Grade 1 = 7.5%), 2)Lymph node(Yes = 87.5%, No = 12.5%), 3)Family cancer history(Yes = 47.5%, No = 41.3%, Unknown = 11.2%), 4) Abortion history(Yes = 36.2%).In silico methods (data gathering, process, and build networks): Gene Expression Omnibus (GEO), a high-throughput genomic database, was queried for miRNAs expression profiles in breast cancer. For Experimental protocol Tissue Processing, Total RNA isolation, complementary DNA(cDNA) synthesis, and quantitative real time PCR (QRT-PCR) analysis were performed. Results: In the present study, we found significant (p.value<0.05) changes in the expression level of miRNAs and DNMTs in patients with breast cancer. In bioinformatics studies, the GEO microarray data set, similar to qPCR results, showed a decreased expression of miRNAs and increased expression of DNMTs in breast cancer. Conclusion: According to the results of the present study, which showed a decrease in the expression of miRNAs and DNMTs in breast cancer, it can be said that these genes can be used as important diagnostic and therapeutic biomarkers in breast cancer.

Keywords: gene expression omnibus, microarray dataset, breast cancer, miRNA, DNMT (DNA methyltransferases)

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Authors: Richard Lewis

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The following assumptions of the Big Bang theory are challenged and found to be false: the cosmological principle, the assumption that all matter formed at the same time and the assumption regarding the cause of the cosmic microwave background radiation. The evolution of the universe is described based on the conclusion that the universe is finite with a space boundary. This conclusion is reached by ruling out the possibility of an infinite universe or a universe which is finite with no boundary. In a finite universe, the centre of the universe can be located with reference to our home galaxy (The Milky Way) using the speed relative to the Cosmic Microwave Background (CMB) rest frame and Hubble's law. This places our home galaxy at a distance of approximately 26 million light years from the centre of the universe. Because we are making observations from a point relatively close to the centre of the universe, the universe appears to be isotropic and homogeneous but this is not the case. The CMB is coming from a source located within the event horizon of the universe. There is sufficient mass in the universe to create an event horizon at the Schwarzschild radius. Galaxies form over time due to the energy released by the expansion of space. Conservation of energy must consider total energy which is mass (+ve) plus energy (+ve) plus spacetime curvature (-ve) so that the total energy of the universe is always zero. The predominant position of galaxy formation moves over time from the centre of the universe towards the boundary so that today the majority of new galaxy formation is taking place beyond our horizon of observation at 14 billion light years.

Keywords: cosmology, dark energy, dark matter, evolution of the universe

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Authors: Ertuğrul Ferhat Yilmaz, Ali Riza Perçin

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In the business enterprises implemented modern business enterprise principles, the most important issues are increasing the performance of workers and getting maximum income. Through the twentieth century, rapid development of the sectors of data processing and communication and because of the free trade politics arising of multilateral business enterprises have canceled the economical borders and changed the local rivalry into the spherical rivalry. In this rivalry conditions, the business enterprises have to work active and productive in order to continue their existences. The employees worked at business enterprises have formed the most important factor of product. Therefore, the business enterprises inferring the importance of the human factors in order to increase the profit have used “the performance evolution system” to increase the success and development of the employees. The evolution of the performance is aimed to increase the manpower productive by using the employees in an active way. Furthermore, this system assists the wage politics implemented in business enterprise, determining the strategically plans in business enterprises through the short and long terms, being promoted and determining the educational needs of employees, making decisions as dismissing and work rotation. It requires a great deal of effort to catch the pace of change in the working realm and to keep up ourselves up-to-date. To get the quality in people,to have an effect in workplace depends largely on the knowledge and competence of managers and prospective managers. Therefore,managers need to use the performance evaluation systems in order to base their managerial decisions on sound data. This study aims at finding whether the organizations effectively use performance evaluation systms,how much importance is put on this issue and how much the results of the evaulations have an effect on employees. Whether the organizations have the advantage of competition and can keep on their activities depend to a large extent on how they effectively and efficiently use their employees.Therefore,it is of vital importance to evaluate employees' performance and to make them better according to the results of that evaluation. The performance evaluation system which evaluates the employees according to the criteria related to that organization has become one of the most important topics for management. By means of those important ends mentioned above,performance evaluation system seems to be a tool that can be used to improve the efficiency and effectiveness of organization. Because of its contribution to organizational success, thinking performance evaluation on the axis of efficiency shows the importance of this study on a different angle. In this study, we have explained performance evaluation system ,efficiency and the relation between those two concepts. We have also analyzed the results of questionnaires conducted on the textile workers in Edirne city.We have got positive answers from the questions about the effects of performance evaluation on efficiency.After factor analysis ,the efficiency and motivation which are determined as factors of performance evaluation system have the biggest variance (%19.703) in our sample. Thus, this study shows that objective performance evaluation increases the efficiency and motivation of employees.

Keywords: performance, performance evolution system, productivity, Edirne region

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Authors: Lorena F. Axinte

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Territorial rescaling is a universal practice in the UK, following a logic of agglomeration and competition as the only chance for cities to thrive. Cardiff Capital Region is one of the latest examples, and its governance structures and developmental narratives are currently being shaped. Its evolution must be compatible with the Wellbeing of Future Generations Act, a Welsh legislation that requires public bodies to put sustainability at the core of all actions. Departing from this case study, the project follows the evolution of Cardiff Capital Region and assesses it based on a new a conceptual framework that connects the notions of regenerative development, collaborative governance, and progressive regionalism. The hypothetical synergies between these different theoretical perspectives are demonstrated, inferring that if regenerative development is aimed at, it must necessarily start with collaborative modes of governance. The objective is to explore (a) whether expanding the network of active stakeholders who get to intervene in the governance structure can contribute to a more progressive definition and development of the city region and (b) whether this can be considered a pathway towards regenerative development. The exploratory fieldwork conducted during the initial phase of the project used qualitative methods, which will be complemented next by different participatory research approaches, as well as a quantitative analysis. Despite being in its early days, the study is showing that a wider range of voices can indeed change priorities, reconcile and balance between the economic drivers and the wider social, economic, cultural and environmental aspects.

Keywords: Cardiff Capital Region, collaborative governance, progressive regionalism, regenerative development

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Authors: Proficiency Munsaka, Peter Baricholo, Erich Rohwer

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Pulse evolutions along the 5 cm long, 6.0 ×4.2 μm² cross-section silicon germanium (SiGe) photonic waveguides were simulated and compared with experiments. Simulations were carried out by solving a generalized nonlinear Schrodinger equation (GNLSE) for an optical pulse evolution along the length of the SiGe photonic waveguides by the split-step Fourier method (SSFM). The solution obtained from the SSFM gave the pulse envelope in both time and spectral domain calculated at each distance step along the propagation direction. The SiGe photonic waveguides were pumped in an anomalous group velocity dispersion (GVD) regime using a 4.7 μm, 210 fs femtosecond laser to produce a significant supercontinuum (SC). The simulated propagation of ultrafast pulse along the SiGe photonic waveguides produced an SC covering the atmospheric window (2.5-8.5 μm) containing the molecular fingerprints for important gases. Thus, the mid-infrared supercontinuum generation in SiGe photonic waveguides system can be commercialized for gas spectroscopy for detecting gases that include CO₂, CH₄, H₂O, SO₂, SO₃, NO₂, H₂S, CO, and NO at trace level using absorption spectroscopy technique. The simulated profile evolutions are spectrally and temporally similar to those obtained by other researchers. Obtained evolution profiles are characterized by pulse compression, Soliton fission, dispersive wave generation, stimulated Raman Scattering, and Four Wave mixing.

Keywords: silicon germanium photonic waveguide, supercontinuum generation, spectroscopy, mid infrared

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Authors: Öznur Saribaş, Si̇bel Kahraman Çeti̇ntaş

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It is aimed to compare target volume and critical organ doses by using CyberKnife (CK) in accelerated partial breast irradiation (APBI) in patients with early stage breast cancer. Three different virtual plans were made for Iris, fixed and multi-leaf collimator (MLC) for 5 patients who received radiotherapy in the CyberKnife system. CyberKnife virtual plans were created, with 6 Gy per day totaling 30 Gy. Dosimetric parameters for the three collimators were analyzed according to the restrictions in the NSABP-39/RTOG 0413 protocol. The plans ensured critical organs were protected and GTV received 95 % of the prescribed dose. The prescribed dose was defined by the isodose curve of a minimum of 80. Homogeneity index (HI), conformity index (CI), treatment time (min), monitor unit (MU) and doses taken by critical organs were compared. As a result of the comparison of the plans, a significant difference was found for the duration of treatment, MU. However, no significant difference was found for HI, CI. V30 and V15 values of the ipsi-lateral breast were found in the lowest MLC. There was no significant difference between Dmax values for lung and heart. However, the mean MU and duration of treatment were found in the lowest MLC. As a result, the target volume received the desired dose in each collimator. The contralateral breast and contralateral lung doses were the lowest in the Iris. Fixed collimator was found to be more suitable for cardiac doses. But these values did not make a significant difference. The use of fixed collimators may cause difficulties in clinical applications due to the long treatment time. The choice of collimator in breast SBRT applications with CyberKnife may vary depending on tumor size, proximity to critical organs and tumor localization.

Keywords: APBI, CyberKnife, early stage breast cancer, radiotherapy.

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Authors: Runliang Wang, Jianhua Liu, Duo Jia, Xiaoyu Ding

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The contact between sealing surfaces plays a vital role in guaranteeing the sealing performance of various seals. To date, analyses of sealing structures have rarely considered both structural parameters (macroscale) and surface roughness information (microscale) of sealing surfaces due to the complex modeling process. Meanwhile, most of the contact analyses applied to seals were conducted only under normal loading, which still existssome distance from real loading conditions in engineering. In this paper, a multiscale rough contact model, which took both macrostructural parameters of seals and surface roughness information of sealing surfaces into consideration for the cone-cone seal, was established. By using the finite element method (FEM), the combined normal and tangential loading was applied to the model to simulate the assembly process of the cone-cone seal. The evolution of the contact behaviors during the assembly process, such as the real contact area (RCA), the distribution of contact pressure, and contact status, are studied in detail. The results showed the non-linear relationship between the RCA and the load, which was different from the normal loading cases. In addition, the evolution of the real contact area of cone-cone seals with isotropic and anisotropic rough surfaces are also compared quantitatively.

Keywords: contact mechanics, FEM, randomly rough surface, real contact area, sealing

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Authors: Kuan Yin Hsiao, Shyh Ming Kuo, Yi Jhen Wu, Chin Wen Chuang, Chuen-Fu Lin, Wei-qing Yang, Han Hsiang Huang

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Anti-tumor effects of natural products, like compounds from marine sponges and soft corals, have been investigated for decades. Polymeric nanoparticles prepared from biodegradable and biocompatible molecules, such as Hyaluronan (HA), Chitosan (CHI) and gelatin have been widely studied. Encapsulation of anti-cancer therapies by the biopolymeric nanoparticles in drug delivery system is potentially capable of improving the therapeutic effects and attenuating their toxicity. In the current study, the anti-bladder cancer effects of heteronemin extracted from the sponge Hippospongia sp. with or without HA and CHI nanoparticle encapsulation were assessed and evaluated in vitro. Results showed that IC50 (half maximal inhibitory concentration) of heteronemin toward T24 human bladder cancer cell viability is approximately 0.18 µg/mL. Both plain and HA nanoparticles-encapsulated heteronemin at 0.2 and 0.4 µg/mL significantly reduced T24 cell viability (P<0.001) while HA nanoparticles-encapsulated heteronemin showed weaker viability-inhibitory effects on L929 fibroblasts compared with plain heteronemin at the identical concentrations. HA and CHI nanoparticles-encapsulated heteronemin exhibited significantly stronger inhibitory effects against migration of T24 human bladder cancer cell than those exerted by plain heteronemin at the same concentrations (P<0.001). The flow cytometric results showed that 0.2 µg/mL HA and CHI nanoparticles-encapsulated heteronemin induced higher early apoptosis rate than that induced by plain heteronemin at the same concentration. These results show that HA and CHI nanoparticle encapsulation is able to elevate anti-migratory and apoptosis-inducing effects exerted by heteronemin against bladder cancer cells in vitro. The in vivo anti-bladder cancer effects of the compound with or without HA/CHI nanoparticle encapsulation will be further investigated and examined using murine tumor models. The data obtained from this study will extensively evaluate of the anti-bladder cancer effects of heteronemin as well as HA/CHI-encapsulated heteronemin and pave a way to develop potential bladder cancer treatment.

Keywords: heteronemin, nanoparticles, hyaluronan, chitosan, bladder cancer

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