Search results for: Paraptosis-like program cell death
Commenced in January 2007
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Edition: International
Paper Count: 8108

Search results for: Paraptosis-like program cell death

8018 Sociological Analysis on Prisoners; with Special Reference to Prisoners of Death Penalty and Life Imprisonment in Sri Lanka

Authors: Wasantha Subasinghe

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Crimes are one of big social problems in Sri Lanka. Crimes can be seen as simply way as an activity that against for the society or public law. There are offences in minor crimes and grave crimes including murder, rape, trafficking, robbery, excise, narcotic, kidnapping and so on. There are various forms of punishment such as bailing, fining, and prisoning to the death penalty. Death penalty contains the killing of an offender for an offense. There are 23 prison institutions in Sri Lanka including 03 closed prisoners and 20 remand prisons. There are 10 work camps, 02 open prison camps, 01 training school for youthful offenders and 02 correctional centers for youthful offenders. Capital punishment is legal in Sri Lanka as many other countries as India, Japan, Bangladesh, Iran and Iraq so on. When compared unconvicted prisoners from 2006-2010 there is an increase. It was 89190 in 2006 and it was 100191 in 2010. There were 28732 of convicted prisoners and it was 32128 in 2010. There were 165 Death sentences in 2006 and it was 96 in 2010. There are 540 individuals had been sentenced to death. The death penalty has not been implemented in Sri Lanka since 1976. Research problem: What are the feelings of prisoners as waiting for death?’ Objectives of the study were identifying prisoners’ point of view on their punishment and root causes for their offence. Case studies were conducted to identify the research problem and data were collected using formal interviews. Research area was Welikada prison. Stratified sampling method in probability samplings was used. Sample size was 20 cases from death penalty and life in prison prisoners and 20 from other convicted prisoners. Findings revealed causes and feelings them as offenders. They need if death penalty or freedom. Some of them need to convert death sentence to life imprisonment. They are physically and mentally damaged after their imprisonment. Lack of hope and as well as lack of welfare and rehabilitation programs they suffered their lives.

Keywords: death penalty, expectations, life imprisonment, rehabilitation

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8017 The Toxic Effects of Kynurenine Metabolites on SH-SY5Y Neuroblastoma Cells

Authors: Susan Hall, Gary D. Grant, Catherine McDermott, Devinder Arora

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Introduction /Aim: The kynurenine pathway is thought to play an important role in the pathophysiology of numerous neurodegenerative diseases including depression, Alzheimer’s disease, and Parkinson’s disease. Numerous neuroactive compounds, including the neurotoxic 3-hydroxyanthranilic acid, 3-hydroxykynurenine and quinolinic acid and the neuroprotective kynurenic acid and picolinic acid, are produced through the metabolism of kynurenine and are thought to be the causative agents responsible for neurodegeneration. The toxicity of 3-hydroxykynurenine, 3-hydroxyanthranilic acid and quinolinic acid has been widely evaluated and demonstrated in primary cell cultures but to date only 3-hydroxykynurenine and 3-hydroxyanthranilic acid have been shown to cause toxicity in immortal tumour cells. The aim of this study was to evaluate the toxicity of kynurenine metabolites, both individually and in combination, on SH-SY5Y neuroblastoma cells after 24 and 72 h exposure in order to explore a cost-effective model to study their neurotoxic effects and potential protective agents. Methods: SH-SY5Y neuroblastoma cells were exposed to various concentrations of the neuroactive kynurenine metabolites, both individually and in combination, for 24 and 72 h, and viability was subsequently evaluated using the Resazurin (Alamar blue) proliferation assay. Furthermore, the effects of these compounds, alone and in combination, on specific death pathways including apoptosis, necrosis and free radical production was evaluated using various assays. Results: Consistent with literature, toxicity was shown with short-term 24-hour treatments at 1000 μM concentrations for both 3-hydroxykynurenine and 3-hydroxyanthranilic acid. Combinations of kynurenine metabolites showed modest toxicity towards SH-SY5Y neuroblastoma cells in a concentration-dependent manner. Specific cell death pathways, including apoptosis, necrosis and free radical production were shown to be increased after both 24 and 72 h exposure of SH-SY5Y neuroblastoma cells to 3-hydroxykynurenine and 3-hydroxyanthranilic acid and various combinations of neurotoxic kynurenine metabolites. Conclusion: It is well documented that neurotoxic kynurenine metabolites show toxicity towards primary human neurons in the nanomolar to low micromolar concentration range. Results show that the concentrations required to show significant cell death are in the range of 1000 µM for 3-hydroxykynurenine and 3-hydroxyanthranilic acid and toxicity of quinolinic acid towards SH-SY5Y was unable to be shown. This differs significantly from toxicities observed in primary human neurons. Combinations of the neurotoxic metabolites were shown to have modest toxicity towards these cells with increased toxicity and activation of cell death pathways observed after 72 h exposure. This study suggests that the 24 h model is unsuitable for use in neurotoxicity studies, however, the 72 h model better represents the observations of the studies using primary human neurons and may provide some benefit in providing a cost-effective model to assess possible protective agents against kynurenine metabolite toxicities.

Keywords: kynurenine metabolites, neurotoxicity, quinolinic acid, SH-SY5Y neuroblastoma

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8016 Cellular Mechanisms Involved in the Radiosensitization of Breast- and Lung Cancer Cells by Agents Targeting Microtubule Dynamics

Authors: Elsie M. Nolte, Annie M. Joubert, Roy Lakier, Maryke Etsebeth, Jolene M. Helena, Marcel Verwey, Laurence Lafanechere, Anne E. Theron

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Treatment regimens for breast- and lung cancers may include both radiation- and chemotherapy. Ideally, a pharmaceutical agent which selectively sensitizes cancer cells to gamma (γ)-radiation would allow administration of lower doses of each modality, yielding synergistic anti-cancer benefits and lower metastasis occurrence, in addition to decreasing the side-effect profiles. A range of 2-methoxyestradiol (2-ME) analogues, namely 2-ethyl-3-O-sulphamoyl-estra-1,3,5 (10) 15-tetraene-3-ol-17one (ESE-15-one), 2-ethyl-3-O-sulphamoyl-estra-1,3,5(10),15-tetraen-17-ol (ESE-15-ol) and 2-ethyl-3-O-sulphamoyl-estra-1,3,5(10)16-tetraene (ESE-16) were in silico-designed by our laboratory, with the aim of improving the parent compound’s bioavailability in vivo. The main effect of these compounds is the disruption of microtubule dynamics with a resultant mitotic accumulation and induction of programmed cell death in various cancer cell lines. This in vitro study aimed to determine the cellular responses involved in the radiation sensitization effects of these analogues at low doses in breast- and lung cancer cell lines. The oestrogen receptor positive MCF-7-, oestrogen receptor negative MDA-MB-231- and triple negative BT-20 breast cancer cell lines as well as the A549 lung cancer cell line were used. The minimal compound- and radiation doses able to induce apoptosis were determined using annexin-V and cell cycle progression markers. These doses (cell line dependent) were used to pre-sensitize the cancer cells 24 hours prior to 6 gray (Gy) radiation. Experiments were conducted on samples exposed to the individual- as well as the combination treatment conditions in order to determine whether the combination treatment yielded an additive cell death response. Morphological studies included light-, fluorescence- and transmission electron microscopy. Apoptosis induction was determined by flow cytometry employing annexin V, cell cycle analysis, B-cell lymphoma 2 (Bcl-2) signalling, as well as reactive oxygen species (ROS) production. Clonogenic studies were performed by allowing colony formation for 10 days post radiation. Deoxyribonucleic acid (DNA) damage was quantified via γ-H2AX foci and micronuclei quantification. Amplification of the p53 signalling pathway was determined by western blot. Results indicated that exposing breast- and lung cancer cells to nanomolar concentrations of these analogues 24 hours prior to γ-radiation induced more cell death than the compound- and radiation treatments alone. Hypercondensed chromatin, decreased cell density, a damaged cytoskeleton and an increase in apoptotic body formation were observed in cells exposed to the combination treatment condition. An increased number of cells present in the sub-G1 phase as well as increased annexin-V staining, elevation of ROS formation and decreased Bcl-2 signalling confirmed the additive effect of the combination treatment. In addition, colony formation decreased significantly. p53 signalling pathways were significantly amplified in cells exposed to the analogues 24 hours prior to radiation, as was the amount of DNA damage. In conclusion, our results indicated that pre-treatment of breast- and lung cancer cells with low doses of 2-ME analogues sensitized breast- and lung cancer cells to γ-radiation and induced apoptosis more so than the individual treatments alone. Future studies will focus on the effect of the combination treatment on non-malignant cellular counterparts.

Keywords: cancer, microtubule dynamics, radiation therapy, radiosensitization

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8015 The Effect of Naringenin on the Apoptosis in T47D Cell Line of Breast Cancer

Authors: AliAkbar Hafezi, Jahanbakhsh Asadi, Majid Shahbazi, Alijan Tabarraei, Nader Mansour Samaei, Hamed Sheibak, Roghaye Gharaei

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Background: Breast cancer is the most common cancer in women. In most cancer cells, apoptosis is blocked. As for the importance of apoptosis in cancer cell death and the role of different genes in its induction or inhibition, the search for compounds that can begin the process of apoptosis in tumor cells is discussed as a new strategy in anticancer drug discovery. The aim of this study was to investigate the effect of Naringenin (NGEN) on the apoptosis in the T47D cell line of breast cancer. Materials and Methods: In this experimental study in vitro, the T47D cell line of breast cancer was selected as a sample. The cells at 24, 48, and 72 hours were treated with doses of 20, 200, and 1000 µm of Naringenin. Then, the transcription levels of the genes involved in apoptosis, including Bcl-2, Bax, Caspase 3, Caspase 8, Caspase 9, P53, PARP-1, and FAS, were assessed using Real Time-PCR. The collected data were analyzed using IBM SPSS Statistics 24.0. Results: The results showed that Naringenin at doses of 20, 200, and 1000 µm in all three times of 24, 48, and 72 hours increased the expression of Caspase 3, P53, PARP-1 and FAS and reduced the expression of Bcl-2 and increased the Bax/Bcl-2 ratio, nevertheless in none of the studied doses and times, had not a significant effect on the expression of Bax, Caspase 8 and Caspase 9. Conclusion: This study indicates that Naringenin can reduce the growth of some cancer cells and cause their deaths through increased apoptosis and decreased anti-apoptotic Bcl-2 gene expression and, resulting in the induction of apoptosis via both internal and external pathways.

Keywords: apoptosis, breast cancer, naringenin, T47D cell line

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8014 An Interpretative Phenomenological Analysis of the Death Practices and Rituals of the Isneg People in Apayao

Authors: Ivy Angelique Malit, Marion Nicole Dela Vega, Marjorie Mae Mendoza

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Death practices and rituals of the Philippines is rich with facts about our history mostly on our beliefs of the afterlife before the arrival of the western culture which is still being practiced by the indigenous people of the Philippines. The death practices and rituals are acts of showing the inner thoughts, and feelings towards the person who died. The meanings behind those practices and rituals become the reason why the indigenous people still treasure these death practices and rituals as a part of their culture. This study seeks to know the experiences of the death practices and rituals of one of the Indigenous groups in Apayao, the Isnegs and the meaning of those experiences. The researchers aimed to look at it on a psychological lens. In which the researchers aim (1) to know their experiences of their death practices from the perspective of their thoughts, feelings and actions, and (2) to seek the meaning behind their death rituals. The design used in the research is a qualitative design and Interpretative Phenomenological Analysis. The participants were gathered by using purposive sampling. The researchers gathered the data from a form of a semi-structured interview with guide questions. The researchers used Thematic Analysis to analyze the verbatim transcriptions from the interview. The experiences of death practices and rituals of the Isneg people have been presented in the aspects of their thoughts, feelings and behavior. The experiences were presented with 7 superordinate themes namely, (1) Refusal of Reality (2) Feelings of mixed emotions (3) Oblivious Acts of the participants (4) Conflict with self and culture (5) Negative thinking of the participants (6) Process of Acceptance (8) Act of Love. The make meaning behind the death practices and rituals of the Isneg people have been presented with 2 superordinate themes, (1) Act of Respect and (2) Act of Loyalty. The results of the research show that the experiences and meaning behind their death practices and burials were being based more by their own beliefs. In their culture, which has been passed through by their ancestors and becomes the foundation of their beliefs and their newly found religion which was introduced by the travelling missionaries. Doing those death practices and rituals is their way to show their affections, like respect and loyalty towards the person who died.

Keywords: death practices, interpretative phenomenological analysis, isneg people, rituals, theory of grieving

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8013 Building in-Addition-School-Family Partnership

Authors: Lulu Sun

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In Addition is an after-school mathematics program in which students and their parents build mathematical confidence and competence by solving problems they curious about. It is a program consists of mix-grade from 4th to 6th grade of 10 to 20 students, including math problem solving and other activities. This partnership will focus on the relationship between the In-Addition and the parents’ engagement; in this kind of partnership, it has the In-Addition program teaching and the family engagement. This partnership is purpose to building cooperation between the program and parents, strengthening the links between the program and families.

Keywords: program-family, family engagement, positive bias, partnership

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8012 Death Anxiety and Life Expectancy among Older Adults in Iran

Authors: Vahid Rashedi, Banafsheh Ebrahimi, Mahtab Sharif Mohseni, Mohammadali Hosseini

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Introduction: One of the metrics used to evaluate health status is life expectancy. This index alters as people age as a result of several events, illnesses, stress, and anxiety. One of the issues that might develop into a lethal phobia is death anxiety. This study looked at older persons in Tehran, Iran, to see if there was any correlation between life expectancy and fear of dying. Methods: Cluster random sampling was used to select 208 older persons (age 60) who had been sent to adult daycare facilities in Tehran for this correlational descriptive study. A demographic questionnaire, Temper's death anxiety scale, and Snyder's life expectancy scale were used to gather the data. Statistical Package for the Social Sciences softwear version 22 was used to conduct the data analysis. Results: The average age of the senior citizens was 66.60 (6.58) years. With a mean life expectancy of 24.94, it was discovered that the average death anxiety was 12.21. Additionally, Pearson's correlation coefficient demonstrated a bad correlation between fear of dying and life expectancy. Age, residential status, and death fear were the three primary predictors of a decline in life expectancy, according to multiple regression analysis. Conclusion: The findings suggest that there is a link between death fear and a lower life expectancy, which calls for the use of appropriate strategies to increase older individuals' life expectancies as well as the teaching of anxiety coping mechanisms.

Keywords: aged, frailty, death, anxiety, life

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8011 A Study of Life Expectancy in an Urban Set up of North-Eastern India under Dynamic Consideration Incorporating Cause Specific Mortality

Authors: Mompi Sharma, Labananda Choudhury, Anjana M. Saikia

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Background: The period life table is entirely based on the assumption that the mortality patterns of the population existing in the given period will persist throughout their lives. However, it has been observed that the mortality rate continues to decline. As such, if the rates of change of probabilities of death are considered in a life table then we get a dynamic life table. Although, mortality has been declining in all parts of India, one may be interested to know whether these declines had appeared more in an urban area of underdeveloped regions like North-Eastern India. So, attempt has been made to know the mortality pattern and the life expectancy under dynamic scenario in Guwahati, the biggest city of North Eastern India. Further, if the probabilities of death changes then there is a possibility that its different constituent probabilities will also change. Since cardiovascular disease (CVD) is the leading cause of death in Guwahati. Therefore, an attempt has also been made to formulate dynamic cause specific death ratio and probabilities of death due to CVD. Objectives: To construct dynamic life table for Guwahati for the year 2011 based on the rates of change of probabilities of death over the previous 10 and 25 years (i.e.,2001 and 1986) and to compute corresponding dynamic cause specific death ratio and probabilities of death due to CVD. Methodology and Data: The study uses the method proposed by Denton and Spencer (2011) to construct dynamic life table for Guwahati. So, the data from the Office of the Birth and Death, Guwahati Municipal Corporation for the years 1986, 2001 and 2011 are taken. The population based data are taken from 2001 and 2011 census (India). However, the population data for 1986 has been estimated. Also, the cause of death ratio and probabilities of death due to CVD are computed for the aforementioned years and then extended to dynamic set up for the year 2011 by considering the rates of change of those probabilities over the previous 10 and 25 years. Findings: The dynamic life expectancy at birth (LEB) for Guwahati is found to be higher than the corresponding values in the period table by 3.28 (5.65) years for males and 8.30 (6.37) years for females during the period of 10 (25) years. The life expectancies under dynamic consideration in all the other age groups are also seen higher than the usual life expectancies, which may be possible due to gradual decline in probabilities of death since 1986-2011. Further, a continuous decline has also been observed in death ratio due to CVD along with cause specific probabilities of death for both sexes. As a consequence, dynamic cause of death probability due to CVD is found to be less in comparison to usual procedure. Conclusion: Since incorporation of changing mortality rates in period life table for Guwahati resulted in higher life expectancies and lower probabilities of death due to CVD, this would possibly bring out the real situation of deaths prevailing in the city.

Keywords: cause specific death ratio, cause specific probabilities of death, dynamic, life expectancy

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8010 Temperature Distribution Control for Baby Incubator System Using Arduino AT Mega 2560

Authors: W. Widhiada, D. N. K. P. Negara, P. A. Suryawan

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The technological advances in the field of health to be very important, especially on the safety of the baby. In this case a lot of premature infants death caused by poorly managed health facilities. Mostly the death of premature baby caused by bacteria since the temperature around the baby is not normal. Related to this, the incubator equipment needs to be important, especially in how to control the temperature in incubator. On/Off controls is used to regulate the temperature distribution in the incubator so that the desired temperature is 36 °C to stay awake and stable. The authors have been observed and analyzed the data to determine the temperature distribution in the incubator using program of MATLAB/Simulink. The output temperature distribution is obtained at 36 °C in 400 seconds using an Arduino AT 2560. This incubator is able to maintain an ambient temperature and maintain the baby's body temperature within normal limits and keep the moisture in the air in accordance with the limit values required in infant incubator.

Keywords: on/off control, distribution temperature, Arduino AT 2560, baby incubator

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8009 New Quinazoline Derivative Induce Cytotoxic Effect against Mcf-7 Human Breast Cancer Cell

Authors: Maryam Zahedi Fard, Nazia Abdul Majid, Hapipah Mohd Ali, Mahmood Ameen Abdulla

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New quinazoline schiff base 3-(5-bromo-2-hydroxy-3-methoxybenzylideneamino)-2-(5-bromo-2-hydroxy-3-methoxyphenyl)-2,3-dihydroquinazolin-4(1H)-one was investigated for anticancer activity against MCF-7 human breast cancer cell line with involved mechanism of apoptosis. The compound demonstrated a remarkable antiproliferative effect, with an IC50 value of 3.41 ± 0.34, after 72 hours of treatment. Morphological apoptotic features in treated MCF-7 cells were observed by AO/PI staining. Furthermore, treated MCF-7 cells subjected to apoptosis death, as exhibited by perturbation of mitochondrial membrane potential and cytochrome c release as well as increase in ROS generation. We also found activation of caspases 3/7 and -9. Moreover, acute toxicity test demonstrated the nontoxic nature of the compound in mice. Our results showed the selected compound significantly induce apoptosis in MCF-7 cells via intrinsic pathway, which might be considered as a potent candidate for further in vivo and clinical breast cancer studies.

Keywords: antiproliferative effect, MCF-7 human breast cancer cell line, apoptosis, caspases

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8008 Preparation of Gramine Nanosuspension and Protective Effect of Gramine on Human Oral Cell Lines by Induction of Apoptosis

Authors: K. Suresh, R. Arunkumar

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The objective of this study is to investigate the preparation of gramine nano suspension and protective effect of Gramine on the apoptosis of laryngeal cancer cells cell line (HEp-2 and KB). The growth inhibition rate of Hep-2 and KB cells in vitro were measured by MTT assay and apoptosis by, levels of reactive oxygen species, mitochondrial membrane potential, morphological changes and flowcytometry. Based on the results, we determined the effective doses of gramine as 127.23µm/ml for 24 hr and 119.81 µm/ml for 48hr in hep-2 cell line and 147.58 µm ml for 24 hr and 123.74µm µm/ml for 48hr in KB cell line. cytotoxicity effects of gramine were confirmed by treatment of HEp-2 cell and KB cell with IC50 concentration of gramine resulted in sequences of events marked by the enhance the apoptosis accompanied by loss of cell viability, modulation of reactive oxygen species and cell cycle arrest through the induction of G0/G1 phase arrest on HEp-2 cells. Our study suggests that the nanosuspension of gramine possesses the more cytotoxic effect of cancer cells and a novel candidate for cancer chemoprevention.

Keywords: apoptosis, HEp-2 cell line, KB cell line mitochondria, gramine, nanosuspension

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8007 Taylor’s Law and Relationship between Life Expectancy at Birth and Variance in Age at Death in Period Life Table

Authors: David A. Swanson, Lucky M. Tedrow

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Taylor’s Law is a widely observed empirical pattern that relates variances to means in sets of non-negative measurements via an approximate power function, which has found application to human mortality. This study adds to this research by showing that Taylor’s Law leads to a model that reasonably describes the relationship between life expectancy at birth (e0, which also is equal to mean age at death in a life table) and variance at age of death in seven World Bank regional life tables measured at two points in time, 1970 and 2000. Using as a benchmark a non-random sample of four Japanese female life tables covering the period from 1950 to 2004, the study finds that the simple linear model provides reasonably accurate estimates of variance in age at death in a life table from e0, where the latter range from 60.9 to 85.59 years. Employing 2017 life tables from the Human Mortality Database, the simple linear model is used to provide estimates of variance at age in death for six countries, three of which have high e0 values and three of which have lower e0 values. The paper provides a substantive interpretation of Taylor’s Law relative to e0 and concludes by arguing that reasonably accurate estimates of variance in age at death in a period life table can be calculated using this approach, which also can be used where e0 itself is estimated rather than generated through the construction of a life table, a useful feature of the model.

Keywords: empirical pattern, mean age at death in a life table, mean age of a stationary population, stationary population

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8006 Health Transformation Program and Effects on Health Expenditures

Authors: Zeynep Karacor, Rahime Hulya Ozturk

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In recent years, the rise of population density and the problem of aging population took attention to the health expenditures. In Turkey, some regulations and infrastructure changes in health sector have occurred. These changes are called Health Transformation Program. The productivity of health services, patient satisfaction, quality of services are tried to be improved with this program. Some radical changes are applied in Turkish economy in this context. The aim of this paper is to present the effects of Health Transformation Program on health expenditures. In the first part of the paper, some information’s about health system and applications in Turkey are discussed. In the second part, the aims of Health Transformation Program are explained. And in the third part the effects of Health Transformation Program on health expenditures are examined.

Keywords: health transformation program, Turkey, health services, health expenditures

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8005 Profiling of Apoptotic Protein Expressions after Trabectedin Treatment in Human Prostate Cancer Cell Line PC-3 by Protein Array Technology

Authors: Harika Atmaca, Emir Bozkurt, Latife Merve Oktay, Selim Uzunoglu, Ruchan Uslu, Burçak Karaca

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Microarrays have been developed for highly parallel enzyme-linked immunosorbent assay (ELISA) applications. The most common protein arrays are produced by using multiple monoclonal antibodies, since they are robust molecules which can be easily handled and immobilized by standard procedures without loss of activity. Protein expression profiling with protein array technology allows simultaneous analysis of the protein expression pattern of a large number of proteins. Trabectedin, a tetrahydroisoquinoline alkaloid derived from a Caribbean tunicate, Ecteinascidia turbinata, has been shown to have antitumor effects. Here, we used a novel proteomic approach to explore the mechanism of action of trabectedin in prostate cancer cell line PC-3 by apoptosis antibody microarray. XTT cell proliferation kit and Cell Death Detection Elisa Plus Kit (Roche) was used for measuring cytotoxicity and apoptosis. Human Apoptosis Protein Array (R&D Systems) which consists of 35 apoptosis related proteins was used to assess the omic protein expression pattern. Trabectedin induced cytotoxicity and apoptosis in prostate cancer cells in a time and concentration-dependent manner. The expression levels of the death receptor pathway molecules, TRAIL-R1/DR4, TRAIL R2/DR5, TNF R1/TNFRSF1A, FADD were significantly increased by 4.0-, 21.0-, 4.20- and 11.5-fold by trabectedin treatment in PC-3 cells. Moreover, mitochondrial pathway related pro-apoptotic proteins Bax, Bad, Cytochrome c, and Cleaved Caspase-3 expressions were induced by 2.68-, 2.07-, 2.8-, and 4.5-fold and the expression levels of anti-apoptotic proteins Bcl-2 and Bcl-XL were reduced by 3.5- and 5.2-fold in PC-3 cells. Proteomic (antibody microarray) analysis suggests that the mechanism of action of trabectedin may be exerted via the induction of both intrinsic and extrinsic apoptotic pathways. The antibody microarray platform can be utilised to explore the molecular mechanism of action of novel anticancer agents.

Keywords: trabectedin, prostate cancer, omic protein expression profile, apoptosis

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8004 Neural Network Analysis Applied to Risk Prediction of Early Neonatal Death

Authors: Amanda R. R. Oliveira, Caio F. F. C. Cunha, Juan C. L. Junior, Amorim H. P. Junior

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Children deaths are traumatic events that most often can be prevented. The technology of prevention and intervention in cases of infant deaths is available at low cost and with solid evidence and favorable results, however, with low access cover. Weight is one of the main factors related to death in the neonatal period, so the newborns of low birth weight are a population at high risk of death in the neonatal period, especially early neonatal period. This paper describes the development of a model based in neural network analysis to predict the mortality risk rating in the early neonatal period for newborns of low birth weight to identify the individuals of this population with increased risk of death. The neural network applied was trained with a set of newborns data obtained from Brazilian health system. The resulting network presented great success rate in identifying newborns with high chances of death, which demonstrates the potential for using this tool in an integrated manner to the health system, in order to direct specific actions for improving prognosis of newborns.

Keywords: low birth weight, neonatal death risk, neural network, newborn

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8003 To Stay or to Go: The Death Penalty Phenomenon and the Dilemma of the Nigerian Government

Authors: James Etim Archibong

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The death penalty, to be or not to be, is a topical and hugely divisive issue in several countries. The United Nations recommends its universal abolition. Europe has abolished it, while some countries limit the practice to heinous crimes. Nigeria is one of the countries that have retained the death penalty. In 2004, the federal government placed a moratorium on execution, which was breached in 2006, 2013 and 2016. Nigeria currently has about three thousand inmates on death row because governors are reluctant to sign execution warrants. Human rights groups have consistently called for its abolition in Nigeria, but this has been rebuffed by the government. Nigeria currently finds itself in a dilemma between the global campaign to end the practice and the local support for its retention. This paper, employing a doctrinal approach, examines the concept of capital punishment in Nigeria from the first execution in 1971 to date. It has also examined the debate to abolish or retain it against the backdrop of Nigeria’s present social, economic and multicultural circumstances. It finds that the death penalty is a human right issue and Nigeria should join the majority of states that have dispensed with the practice. While the government contemplates which way to go, amid the impasse, the paper recommends, in the interim, an official, legally backed a moratorium on execution; commuting of death sentences to life imprisonment, and eventually expunging it from the constitution in the ongoing constitutional review.

Keywords: death penalty, capital punishment, human rights, deterrence, right to life

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8002 Autophagy in the Midgut Epithelium of Spodoptera exigua Hübner (Lepidoptera: Noctuidae) Larvae Exposed to Various Cadmium Concentration - 6-Generational Exposure

Authors: Magdalena Maria Rost-Roszkowska, Alina Chachulska-Żymełka, Monika Tarnawska, Maria Augustyniak, Alina Kafel, Agnieszka Babczyńska

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Autophagy is a form of cell remodeling in which an internalization of organelles into vacuoles that are called autophagosomes occur. Autophagosomes are the targets of lysosomes, thus causing digestion of cytoplasmic components. Eventually, it can lead to the death of the entire cell. However, in response to several stress factors, e.g., starvation, heavy metals (e.g., cadmium) autophagy can also act as a pro-survival factor, protecting the cell against its death. The main aim of our studies was to check if the process of autophagy, which could appear in the midgut epithelium after Cd treatment, can be fixed during the following generations of insects. As a model animal, we chose the beet armyworm Spodoptera exigua Hübner (Lepidoptera: Noctuidae), a well-known polyphagous pest of many vegetable crops. We analyzed specimens at final larval stage (5th larval stage), due to its hyperfagy, resulting in great amount of cadmium assimilate. The culture consisted of two strains: a control strain (K) fed a standard diet, and a cadmium strain (Cd), fed on standard diet supplemented with cadmium (44 mg Cd per kg of dry weight of food) for 146 generations, both strains. In addition, the control insects were transferred to the Cd supplemented diet (5 mg Cd per kg of dry weight of food, 10 mg Cd per kg of dry weight of food, 20 mg Cd per kg of dry weight of food, 44 mg Cd per kg of dry weight of food). Therefore, we obtained Cd1, Cd2, Cd3 and KCd experimental groups. Autophagy has been examined using transmission electron microscope. During this process, degenerated organelles were surrounded by a membranous phagophore and enclosed in an autophagosome. Eventually, after the autophagosome fused with a lysosome, an autolysosome was formed and the process of the digestion of organelles began. During the 1st year of the experiment, we analyzed specimens of 6 generations in all the lines. The intensity of autophagy depends significantly on the generation, tissue and cadmium concentration in the insect rearing medium. In the Ist, IInd, IIIrd, IVth, Vth and VIth generation the intensity of autophagy in the midguts from cadmium-exposed strains decreased gradually according to the following order of strains: Cd1, Cd2, Cd3 and KCd. The higher amount of cells with autophagy was observed in Cd1 and Cd2. However, it was still higher than the percentage of cells with autophagy in the same tissues of the insects from the control and multigenerational cadmium strain. This may indicate that during 6-generational exposure to various Cd concentration, a preserved tolerance to cadmium was not maintained. The study has been financed by the National Science Centre Poland, grant no 2016/21/B/NZ8/00831.

Keywords: autophagy, cell death, digestive system, ultrastructure

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8001 Immunomodulatory Role of Heat Killed Mycobacterium indicus pranii against Cervical Cancer

Authors: Priyanka Bhowmik, Subrata Majumdar, Debprasad Chattopadhyay

Abstract:

Background: Cervical cancer is the third major cause of cancer in women and the second most frequent cause of cancer related deaths causing 300,000 deaths annually worldwide. Evasion of immune response by Human Papilloma Virus (HPV), the key contributing factor behind cancer and pre-cancerous lesions of the uterine cervix, makes immunotherapy a necessity to treat this disease. Objective: A Heat killed fraction of Mycobacterium indicus pranii (MIP), a non-pathogenic Mycobacterium has been shown to exhibit cytotoxic effects on different cancer cells, including human cervical carcinoma cell line HeLa. However, the underlying mechanisms remain unknown. The aim of this study is to decipher the mechanism of MIP induced HeLa cell death. Methods: The cytotoxicity of Mycobacterium indicus pranii against HeLa cells was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Apoptosis was detected by annexin V and Propidium iodide (PI) staining. The assessment of reactive oxygen species (ROS) generation and cell cycle analysis were measured by flow cytometry. The expression of apoptosis associated genes was analyzed by real time PCR. Result: MIP could inhibit the proliferation of HeLa cell in a time and dose dependent manner but caused minor damage to normal cells. The induction of apoptosis was confirmed by the cell surface presentation of phosphatidyl serine, DNA fragmentation, and mitochondrial damage. MIP caused very early (as early as 30 minutes) transcriptional activation of p53, followed by a higher activation (32 fold) at 24 hours suggesting prime importance of p53 in MIP-induced apoptosis in HeLa cell. The up regulation of p53 dependent pro-apoptotic genes Bax, Bak, PUMA, and Noxa followed a lag phase that was required for the transcriptional p53 program. MIP also caused the transcriptional up regulation of Toll like receptor 2 and 4 after 30 minutes of MIP treatment suggesting recognition of MIP by toll like receptors. Moreover, MIP caused the inhibition of expression of HPV anti apoptotic gene E6, which is known to interfere with p53/PUMA/Bax apoptotic cascade. This inhibition might have played a role in transcriptional up regulation of PUMA and subsequently apoptosis. ROS was generated transiently which was concomitant with the highest transcription activation of p53 suggesting a plausible feedback loop network of p53 and ROS in the apoptosis of HeLa cells. Scavenger of ROS, such as N-acetyl-L-cysteine, decreased apoptosis suggesting ROS is an important effector of MIP induced apoptosis. Conclusion: Taken together, MIP possesses full potential to be a novel therapeutic agent in the clinical treatment of cervical cancer.

Keywords: cancer, mycobacterium, immunity, immunotherapy.

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8000 Neuroprotective Effect of Germinated Dolichos lablab on 6-Hydroxy Dopamine (6-OHDA) Induced Toxicity in SH-SY5Y Neuroblastoma Cell

Authors: Taek Hwan Lee, Moon Ho Do, Lalita Subedi, Young Un Park, Sun Yeou Kim

Abstract:

Natural and artificial toxic substances namely neurotoxins induce the bitter effect in the nervous system termed as neurotoxicity. It can modulate the normal functioning of the nervous system either hyperactivate it or damage homeostasis of neuronal system. Neurotoxins induced toxicity ultimately kills the neuron. The present study investigated the neuroprotective effects of germinated Dolichos lablab on 6-hydroxydopamine (6-OHDA)-induced neurotoxicity using SH-SY5Y neuroblastoma cells. Germination is a process of plant growth from a seed. Sprouting of a seedling from a seed induced many molecular changes in the seed in order to prepare it for further growth. Because of these molecular and chemical changes, the neuroprotective effect of Dolichos lablab is higher in the germinated form than in the normal condition. SH-SY5Y cells were treated with Dolichos lablab extract (50, 100 g/ml) followed by 6-OHDA (25M) induced toxicity. Cell Viability was measured to check the cell survival against 6-OHDA induced toxicity using MTT assay. Dolichos lablab showed a neuroprotective effect against 6-OHDA induced neuronal cell death in neuroblastoma cell at a higher concentration of 100g/ml however the effect is much better even at the lower concentration after germination 50g/ml. Cell survival was increased dramatically after 15 h of germination and increased with time of germination in concentration dependent manner. Trigonelline as a representative compound was validated in germinated Dolichos lablab by HPLC analysis that might enhance the neuroprotective effect of Dolichos lablab. This result suggests that Dolichos lablab possess neuroprotective effect in neuroblastoma cells against 6-OHDA however its activity was more potent in the germinated form.

Keywords: dolichos lablab, germination, neuroprotection, trigonelline

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7999 Time of Death Determination in Medicolegal Death Investigations

Authors: Michelle Rippy

Abstract:

Medicolegal death investigation historically is a field that does not receive much research attention or advancement, as all of the subjects are deceased. Public health threats, drug epidemics and contagious diseases are typically recognized in decedents first, with thorough and accurate death investigations able to assist in epidemiology research and prevention programs. One vital component of medicolegal death investigation is determining the decedent’s time of death. An accurate time of death can assist in corroborating alibies, determining sequence of death in multiple casualty circumstances and provide vital facts in civil situations. Popular television portrays an unrealistic forensic ability to provide the exact time of death to the minute for someone found deceased with no witnesses present. The actuality of unattended decedent time of death determination can generally only be narrowed to a 4-6 hour window. In the mid- to late-20th century, liver temperatures were an invasive action taken by death investigators to determine the decedent’s core temperature. The core temperature was programmed into an equation to determine an approximate time of death. Due to many inconsistencies with the placement of the thermometer and other variables, the accuracy of the liver temperatures was dispelled and this once common place action lost scientific support. Currently, medicolegal death investigators utilize three major after death or post-mortem changes at a death scene. Many factors are considered in the subjective determination as to the time of death, including the cooling of the decedent, stiffness of the muscles, release of blood internally, clothing, ambient temperature, disease and recent exercise. Current research is utilizing non-invasive hospital grade tympanic thermometers to measure the temperature in the each of the decedent’s ears. This tool can be used at the scene and in conjunction with scene indicators may provide a more accurate time of death. The research is significant and important to investigations and can provide an area of accuracy to a historically inaccurate area, considerably improving criminal and civil death investigations. The goal of the research is to provide a scientific basis to unwitnessed deaths, instead of the art that the determination currently is. The research is currently in progress with expected termination in December 2018. There are currently 15 completed case studies with vital information including the ambient temperature, decedent height/weight/sex/age, layers of clothing, found position, if medical intervention occurred and if the death was witnessed. This data will be analyzed with the multiple variables studied and available for presentation in January 2019.

Keywords: algor mortis, forensic pathology, investigations, medicolegal, time of death, tympanic

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7998 Strategic Management of a Geoscience Education and Training Program

Authors: Lee Ock-Sun

Abstract:

The effective development of a geoscience education and training program takes account of the rapidly changing environment in the geoscience market, includes information about resource-rich countries which have international education demands. In this paper, we introduce the geoscience program run bythe International School for Geoscience Resources at the Korea Institute of Geoscience and Mineral Resources (IS-Geo of KIGAM),and show its remarkable performance. To further effective geoscience program planning and operation, we present recommendations for strategic management for customer-oriented operation with a more favorable program format and advanced training aids. Above all, the IS-Geo of KIGAM should continue improve through‘plan-do-see-feedback’activities based on the recommendations.

Keywords: demand survey, geoscience program, program performance, strategic management

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7997 Dengue Death Review: A Tool to Adjudge the Cause of Dengue Mortality and Use of the Tool for Prevention of Dengue Deaths

Authors: Gagandeep Singh Grover, Vini Mahajan, Bhagmal, Priti Thaware, Jaspreet Takkar

Abstract:

Dengue is a mosquito-borne viral disease endemic in many countries in the tropics and sub-tropics. The state of Punjab in India shows cyclical and seasonal variation in dengue cases. The Case Fatality Rate of Dengue has ranged from 0.6 to 1.0 in the past years. The department has initiated a review of the cases that have died due to dengue in order to know the exact cause of the death in a case of dengue. The study has been undertaken to know the other associated co-morbidities and factors causing death in a case of dengue. The study used the predesigned proforma on which the records (medical and Lab) were recorded and reviewed by the expert committee of the doctors. This study has revealed that cases of dengue having co-morbidities have a longer stay in the hospital. Fluid overload and co-morbidities have been found as major factors leading to death, however, in a confirmed case of dengue hepatorenal shutdown was found to be a major cause of mortality. The data obtained will help in sensitizing the treating physicians in order to decrease the mortality due to dengue in future.

Keywords: dengue, death, morbidities, DHF, DSS

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7996 The Different Essence of Death in the Elegies of Shelley's Adonais and Lord Tennyson's In Memoriam

Authors: Sulistyaningtyas

Abstract:

The topic about death and dying is interesting to discuss since it is strongly related to every individual life. As represented in its title, Adonais: An Elegy on the Death of John Keats is a mournful poem written in 1821 by Percy Bysshe Shelley to mourn the loss of young poet John Keats. To compare, In Memoriam A.H.H. is an elegy written in 1850 about the death of Lord Tennyson’s dearest friend, Arthur Henry Hallam. Although both elegies were written to grieve the authors’ loved ones, their grief affects differently to the psychological being of the narrators. Thus, this research aims to examine the essence of death in affecting the narrators psychologically. By using psychoanalytic criticism, this research reveals the different essence of death in the two elegies as the result of the analysis. Moreover, these two elegies also portray the concept of the afterlife, immortality, and the figure of God. In Adonais, the grief of the narrator to Keats leads him to question the very purpose of life. The loss of his favorite poet which makes him feel sorrowful and mad along his 55 stanzas brings him to a higher psychological level to understand himself. He even sees himself as a Christ-like figure, which shows the idea that God is imaginable. Different from Adonais, the narrator of In Memoriam finds something more spiritual by doing his passionate mourning to Hallam. Through some contemplation in his 133 cantos, in the end, he is convinced that the dear one now dwells with a great Spirit who controls the world. He believes that all of the creation in the universe has to follow one law which is set by God. Hence, it can be concluded that death might bring different consequence to the psyche of every living creature.

Keywords: elegy, comparative study, psychoanalytic criticism, the essence of death

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7995 Pathogenic Effects of IgG and IgM Apoptotic Cell-Reactive Monoclonal Auto-Antibodies on Innate and Adaptive Immunity in Lupus

Authors: Monika Malik, Pooja Arora, Ruchi Sachdeva, Vishnampettai G. Ramachandran, Rahul Pal

Abstract:

Apoptotic debris is believed to be the antigenic trigger in lupus. Whether such debris and autoantibodies induced in lupus-prone mice which specifically recognize its constituents can mediate differential effects on innate and humoral responses in such mice was assessed. The influence of apoptotic blebs and apoptotic cell-reactive monoclonal antibodies on phenotypic markers expressed on bone marrow-derived dendritic cells (BMDCs) and secreted cytokines were evaluated. Sera from lupus-prone and healthy mice immunized with the antibodies were analyzed for anti-self reactivity. Apoptotic blebs, as well as somatically-mutated IgG and non-mutated IgM apoptotic-cell reactive monoclonal antibodies, induced the preferential maturation of BMDCs derived from lupus-prone mice relative to BMDCs derived from healthy mice; antibody specificity and cell genotype both influenced the secretion of inflammatory cytokines. Immunization of lupus-prone mice with IgM and IgG antibodies led to hypergammaglobulinemia; elicited antibodies were self-reactive, and exhibited enhanced recognition of lupus-associated autoantigens (dsDNA, Ro60, RNP68, and Sm) in comparison with adjuvant-induced sera. While ‘natural’ IgM antibodies are believed to contribute to immune homeostasis, this study reveals that apoptotic cell-reactive IgM antibodies can promote inflammation and drive anti-self responses in lupus. Only in lupus-prone mice did immunization with IgG auto-antibodies enhance the kinetics of humoral anti-self responses, resulting in advanced-onset glomerulosclerosis. This study reveals that preferential innate and humoral recognition of the products of cell death in an autoimmune milieu influences the indices associated with lupus pathology.

Keywords: antigen spreading, apoptotic cell-reactive pathogenic IgG, and IgM autoantibodies, glomerulosclerosis, lupus

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7994 Study of Magnetic Nanoparticles’ Endocytosis in a Single Cell Level

Authors: Jefunnie Matahum, Yu-Chi Kuo, Chao-Ming Su, Tzong-Rong Ger

Abstract:

Magnetic cell labeling is of great importance in various applications in biomedical fields such as cell separation and cell sorting. Since analytical methods for quantification of cell uptake of magnetic nanoparticles (MNPs) are already well established, image analysis on single cell level still needs more characterization. This study reports an alternative non-destructive quantification methods of single-cell uptake of positively charged MNPs. Magnetophoresis experiments were performed to calculate the number of MNPs in a single cell. Mobility of magnetic cells and the area of intracellular MNP stained by Prussian blue were quantified by image processing software. ICP-MS experiments were also performed to confirm the internalization of MNPs to cells. Initial results showed that the magnetic cells incubated at 100 µg and 50 µg MNPs/mL concentration move at 18.3 and 16.7 µm/sec, respectively. There is also an increasing trend in the number and area of intracellular MNP with increasing concentration. These results could be useful in assessing the nanoparticle uptake in a single cell level.

Keywords: magnetic nanoparticles, single cell, magnetophoresis, image analysis

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7993 In-Situ Quasistatic Compression and Microstructural Characterization of Aluminium Foams of Different Cell Topology

Authors: M. A. Islam, P. J. Hazell, J. P. Escobedo, M. Saadatfar

Abstract:

Quasistatic compression and micro structural characterization of closed cell aluminium foams of different pore size and cell distributions has been carried out. Metallic foams have good potential for lightweight structures for impact and blast mitigation and therefore it is important to find out the optimized foam structure (i.e. cell size, shape, relative density, and distribution) to maximize energy absorption. In this paper, we present results for two different aluminium metal foams of density 0.5 g/cc and 0.7 g/cc respectively that have been tested in quasi-static compression. The influence of cell geometry and cell topology on quasistatic compression behavior has been investigated using computed tomography (micro-CT) analysis. The compression behavior and micro structural characterization will be presented.

Keywords: metal foams, micro-CT, cell topology, quasistatic compression

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7992 Exploring the Association between Race and Attitudes toward Physician-Assisted Death; An Analysis of the Gss Dataset

Authors: Seini G. Kaufusi

Abstract:

Background. Physician-assisted death (PAD) has and continues to be a controversial issue in the U.S. Dying with dignity statutes exists in 9 U.S. jurisdictions that permit competent adults diagnosed with a terminal illness and given a prognosis of 6 month or less to live to request medication to hasten death. Robust advocacy for and against PAD influences policy, and opinions vary. Aim. This study aims to explore the association between race and the attitudes toward physician-assisted death in the U.S. Methods. Data for this study derives from the General Social Survey (GSS) dataset, a national survey conducted by the National Opinion Research Center (NORC) that focuses on the opinions and values of American’s. A cross-sectional design and probability sample from the 2018 data set was used to randomly select respondents. Results. The results indicated that race is significantly associated with attitudes towards physician-assisted death. The level of significance suggests a strong positive association, and the direction indicated that Black and Other racial groups have higher rates of positive decision about PAD. Conclusion. Although attitudes towards PAD varied, Black and other racial groups had favorable decisions for PAD. Further research is crucial in the continuous debate on PAD and understanding the influences of predictors for or against PAD.

Keywords: attitudes, euthanasia, physician-assisted death, race

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7991 Air Conditioning Variation of 1kW Open-Cathode Proton Exchange Membrane (PEM) Fuel Cell

Authors: Mohammad Syahirin Aisha, Khairul Imran Sainan

Abstract:

The PEM fuel cell is a device that generate electric by electrochemical reaction between hydrogen fuel and oxygen in the fuel cell stack. PEM fuel cell consists of an anode (hydrogen supply), a cathode (oxygen supply) and an electrolyte that allow charges move between the two positions of the fuel cell. The only product being developed after the reaction is water (H2O) and heat as the waste which does not emit greenhouse gasses. The performance of fuel cell affected by numerous parameters. This study is restricted to cathode parameters that affect fuel cell performance. At the anode side, the reactant is not going through any changes. Experiments with variation in air velocity (3m/s, 6m/s and 9m/s), temperature (10oC, 20oC, 35oC) and relative humidity (50%, 60%, and 70%) have been carried out. The experiments results are presented in the form of fuel cell stack power output over time, which demonstrate the impacts of the various air condition on the execution of the PEM fuel cell. In this study, the experimental analysis shows that with variation of air conditions, it gives different fuel cell performance behavior. The maximum power output of the experiment was measured at an ambient temperature of 25oC with relative humidity and 9m/s velocity of air.

Keywords: air-breathing PEM fuel cell, cathode side, performance, variation in air condition

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7990 Autophagy Suppresses Bladder Tumor Formation in a Mouse Orthotopic Bladder Tumor Formation Model

Authors: Wan-Ting Kuo, Yi-Wen Liu, Hsiao-Sheng Liu

Abstract:

Annual incidence of bladder cancer increases in the world and occurs frequently in the male. Most common type is transitional cell carcinoma (TCC) which is treated by transurethral resection followed by intravesical administration of agents. In clinical treatment of bladder cancer, chemotherapeutic drugs-induced apoptosis is always used in patients. However, cancers usually develop resistance to chemotherapeutic drugs and often lead to aggressive tumors with worse clinical outcomes. Approximate 70% TCC recurs and 30% recurrent tumors progress to high-grade invasive tumors, indicating that new therapeutic agents are urgently needed to improve the successful rate of overall treatment. Nonapoptotic program cell death may assist to overcome worse clinical outcomes. Autophagy which is one of the nonapoptotic pathways provides another option for bladder cancer patients. Autophagy is reported as a potent anticancer therapy in some cancers. First of all, we established a mouse orthotopic bladder tumor formation model in order to create a similar tumor microenvironment. IVIS system and micro-ultrasound were utilized to noninvasively monitor tumor formation. In addition, we carried out intravesical treatment in our animal model to be consistent with human clinical treatment. In our study, we carried out intravesical instillation of the autophagy inducer in mouse orthotopic bladder tumor to observe tumor formation by noninvasive IVIS system and micro-ultrasound. Our results showed that bladder tumor formation is suppressed by the autophagy inducer, and there are no significant side effects in the physiology of mice. Furthermore, the autophagy inducer upregulated autophagy in bladder tissues of the treated mice was confirmed by Western blot, immunohistochemistry, and immunofluorescence. In conclusion, we reveal that a novel autophagy inducer with low side effects suppresses bladder tumor formation in our mouse orthotopic bladder tumor model, and it provides another therapeutic approach in bladder cancer patients.

Keywords: bladder cancer, transitional cell carcinoma, orthotopic bladder tumor formation model, autophagy

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7989 Enhancing Sensitization of Cervical Cancer Cells to γ-Radiation Ellagic Acid

Authors: Vidhula Ahire, Amit Kumar, K. P. Mishra, Gauri Kulkarni

Abstract:

Herbal polyphenols have gained significance because of their increasing promise in prevention and treatment of cancer. Therefore, development of a dietary compound as an effective radiosensitizer and a radioprotector is highly warranted for cervical cancer patients undergoing therapy. This study describes the cytotoxic effects of the flavonoid, ellagic acid (EA) when administered either alone or in combination with gamma radiation on cervical cancer HeLa cells in vitro. Apoptotic index and proliferation were measured by using trypan blue assay. Reproductive cell death was analyzed by clonogenic assay. Propidium iodide staining for flowcytometry was performed to analyze cell cycle modulation. Nuclear and mitochondrial changes were studied with specific dyes. DNA repair kinetics was analyzed by immunofluorescence assay. Evaluation and comparison of EA effects were performed with other clinically used breast cancer drugs. When tumor cells were exposed to 2 and 4 Gy of irradiation in presence of EA (10 μM), it yielded a synergistic cytotoxic effect on cervical cancer cells whereas in NIH3T3 cells it reversed the injury caused by irradiation and abetted in the regaining of normal healthy cells. At 24h ~25foci/cell was observed and 2.6 fold decrease in the mitochondrial membrane potential. Up to 40% cell were arrested in the G1 phase and 20-36% cells exhibited apoptosis. Our results demonstrate the role of increased apoptosis and cell cycle modulation in the mechanism of EA mediated radiosensitization of cervical cancer cells and thus advocating EA as an adjuvant for preclinical trials in cancer chemo- radiotherapy.

Keywords: cervical cancer, ellagic acid, sensitization, radiation therapy

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