Triple trouble: examining the effect of combining mechanical stress, PBMCs and cisplatin on hepG2 cell death

In an attempt to find better cancer treatments, a new mathematical model proposed by Klika & Marsik (2009) suggests that more cancer cells could possibly be killed by applying several stress factors to tumour cells, however only as a simulation in silico. The proposed stresses include healthy cell anti-tumour effect, the biochemical effect exerted by a cytotoxic drug and a newly introduced mechanical stress. The hypothesis entails that upon applying these three stress factors together simultaneously to tumour cells, the concentration of the tumour cells decreases more than if a stress factor was applied alone. The two main objectives in this study are: (1) to test the aforementioned hypothesis for the first time in vitro on HepG2 cells (human hepatocellular carcinoma cell line) and (2) to determine the mode of cancer cell death after applying the stress factors. In vitro experiments were conducted using HepG2 cells and the following stress factors were employed: (1) mechanical stress, (2) Cisplatin and (3) PBMCS (Peripheral Blood Mononuclear Cells) co-culture. The effects of the stress factors on HepG2 cells were assessed for cytotoxicity by MTT assay and the mode of cell death was examined by expression of certain apoptosis-related genes (Bax, XIAP and HSP70) on the RNA level and the cleavage of PARP-1 on the protein level. The percentage of cell survival after 24 hours exposure to the various stresses were as follows: mechanical stress alone (~55%), Cisplatin (~70%), PBMCs co-culture (~69%), mechanical stress & Cisplatin (~35%), mechanical stress & PBMCs (~45%), Cisplatin & PBMCs (~35%) and lastly mechanical stress, Cisplatin & PBMCs (~29%). RNA expression analysis of Bax revealed that most of the single stresses, double stresses and triple stresses employed Bax-dependent pathways for HepG2 cell death except PBMCs co-culture alone and PBMCs combined with mechanical stress. Concerning PARP-1, some of the stress factors caused death of HepG2 cells by apoptosis, employing PARP-1, while others did not, proposing that cells used diverse modes of death after exposure to different stress factors. In summary, the mathematical model was validated in vitro as combining two stress factors increased HepG2 cell death and further to a greater extent when combining the three stress factors together, suggesting that future studies on combined stress factors may lead to novel and more effective cancer-targeted therapy

The role of satiety hormones in developmental programming of obesity, stress, and neuroimmune function

Ghrelin and leptin, two important metabolic hormones involved in regulation of energy balance in the adult, have recently been shown to have a neurotrophic role during early life development in that they regulate neuronal connectivity within regions of the hypothalamus responsible for control of energy balance. Disturbances to the early life nutritional environment including overnutrition have been highly correlated with long-life metabolic problems, such as childhood obesity and its complications. (Throughout this thesis the term overnutrition refers to the neonatally overfed animal model due to litter manipulation and not as a form of malnutrition, which may elicit similar offspring phenotypes.) In addition to their metabolic roles, leptin and ghrelin appear to be important for early brain development, with leptin stimulating and ghrelin inhibiting the establishment of appetite regulatory circuitry. Recent research suggests that the neurodevelopmental actions of leptin and ghrelin are restricted to a crucial developmental period that occurs during the first two weeks after birth in rodents, which in humans this critical period encompasses the third trimester of pregnancy and approximately 1000 days after birth. However, the effects of overnutrition on the developing brain during this period and the mechanisms that underlie neurodevelopmental actions of leptin and ghrelin are currently unknown. It is also unclear whether overnutrition affects brain development in males and females to the same extent. The early developmental period is associated with enhanced neuronal plasticity, and disturbances during this critical time have the potential to program later life health outcomes. It is therefore important to shed further insight into the roles of leptin and ghrelin, to develop interventions that alleviate the incidence of childhood obesity and associated comorbidities. An animal model of childhood obesity in rats was used to investigate the short- and long-term effects of neonatal overfeeding on the leptin and ghrelin system. The animal model was achieved by manipulating litter sizes into control litters of 12 pups and small litters of 4 pups, the later representing the neonatal overfeeding environment. The reduction of litter size immediately after birth, led to a significant increase in dietary intake. Consequently, neonatally overfed pups experienced accelerated weight gain and disrupted circulating leptin and ghrelin levels in comparison to control counterparts. Using this model we examined the short- and long-term effects of neonatal overnutrition on the leptin and ghrelin systems in males and females. We investigated here the effects of neonatal overnutrition on hypothalamic orexigenic and anorexigenic neuronal fibre immunoreactivity and if these changes were mediated by leptin in male rats. We also investigated whether these effects could be normalised by a leptin antagonist. We found that neonatal overnutrition in males was associated with short-term central leptin resistance, altered orexigenic neuronal fibre immunoreactivity and no changes in anorexigenic immunoreactivity. We also found that short-term neonatal leptin antagonism did not reverse excess body weight or hyperleptinemia. Our findings suggest that factors other than leptin contribute to the obese phenotype. Most importantly, we found that in males the early life effects of neonatal overfeeding are partly resolved in adulthood, emphasising the importance of brain plasticity. Interestingly, neonatally overfed females, despite an obese phenotype characterised by hyperleptinemia and increased body weight compared to controls, did not show the same changes in the central feeding circuitry as observed in males. These findings are suggestive of sex differences in the effects of neonatal overfeeding and of differences in the ability of the male and female central systems to respond to challenges in the early life nutritional environment. Similarly to leptin, ghrelin along with its appetite-stimulating role in adults is involved in the establishment of hypothalamic feeding pathways during neonatal development in rodents. Here was investigated long-term effect of neonatal overfeeding on the ghrelin system including the ability of both forms of ghrelin (acyl ghrelin and des-acyl ghrelin) to access the hypothalamus in male rats. We demonstrated that neonatal overfeeding affects the ghrelin system during early life by suppressing circulating ghrelin levels and increasing hypothalamic responsiveness to exogenous acyl but not des-acyl ghrelin. Neonatal overnutrition also affects the ability of acyl ghrelin to reach the hypothalamus. Importantly, the influences of neonatal overnutrition observed during early life were resolved in adulthood. In contrast to males, where neonatal overnutrition resulted in compromised hypothalamic ghrelin signalling, in females, the central ghrelin system and circulating ghrelin remained intact. However, neonatal overnutrition in females was associated with long-term alterations in the capacity for the pituitary gland to respond to ghrelin. Ghrelin has recently been shown to have additional properties to those involved in satiety signalling, including regulation of hypothalamic-pituitary-adrenal (HPA) axis responses to psychological stress, as well as being a potent anti-inflammatory agent. Here were investigated both forms of ghrelin (acyl and des-acyl ghrelin) and their anti-inflammatory activity hypothesising that this activity is mediated via the HPA axis. In experiments where male rats were concomitantly injected with acyl or des-acyl ghrelin and lipopolysaccharide (LPS) acyl, but not des-acyl ghrelin, suppressed the inflammatory cytokine response to LPS. Des-acyl ghrelin also had no effects on components of the HPA axis. Acyl ghrelin, despite stimulating neuronal activation in the paraventricular nucleus of the hypothalamus in vivo and stimulating adrenocorticotropic hormone release from the pituitary in vitro, did not affect the HPA axis response to LPS. These findings suggest acyl ghrelin¿s anti-inflammatory effects are independent of its actions on the HPA axis and have implications for the potential use of this peptide for treatment of inflammatory conditions without compromising HPA axis activity. In conclusion, findings from this thesis indicate that metabolic hormones leptin and ghrelin have immense importance in the development of central centres of energy control and metabolism. Altered nutritional environment during early development affects both leptin and ghrelin systems in the rat, however it resolves to a certain extent in adulthood. Importantly, these central developmental changes mediated by leptin and ghrelin have a strong sex-specific factor. In this thesis we also added to the understanding of the mechanisms by which ghrelin exerts its anti-inflammatory properties, which is of great importance in development of therapeutic strategies for treatment of inflammatory conditions

PENGARUH PENGGUNAAN MEDIA INTERNAL PORTAL PT DIRGANTARA INDONESIA TERHADAP CITRA PERUSAHAAN

Penelitian ini membahas pengaruh penggunaan media internal portal PT Dirgantara Indonesia terhadap citra perusahaan. Tujuan penelitian ini adalah mengetahui seberapa besar pengaruh penggunaan media internal portal PT Dirgantara Indonesia terhadap citra perusahaan. Penelitian ini menggunakan beberapa teori yang relevan seperti komunikasi, public relation, penggunaan media, dan citra perusahaan. Metode penelitian yang digunakan dalam penelitian ini adalah penelitian kuantitatif dengan pendekatan deskriptif. Populasi penelitian ini adalah karyawan PT Dirgantara Indonesia dengan responden sebanyak 160 orang karyawan. Dalam menentukan sampel, digunakan metode nonprobability sampling dengan purpossive sampling. Sementara itu, metode analisis yang digunakan adalah analisis deskriptif, uji hipotesis parsial, regresi sederhana, dan koefisien determinasi. Hasil penelitian ini membuktikan bahwa penggunaan media internal portal PT Dirgantara Indonesia memiliki pengaruh yang signifikan terhadap citra perusahaan dengan persentase sebesar 70,6%. Hal ini menunjukkan bahwa semakin tinggi penggunaan media internal portal PT Dirgantara Indonesia, semakin tinggi dan positif pandangan karyawan terhadap citra perusahaan dalam persepsi mereka.Kata Kunci: media internal, public relation, citra perusahaanThis research discusses the influence of the use of internal media Portal of PT Dirgantara Indonesia to the corporate's image. The purpose of this research is to find the influence of the use of internal media Portal PT Dirgantara Indonesia to the corporate's image. This research used descriptive quantitative research. The population of this research is the employees of PT Dirgantara Indonesia with 160 respondents. The nonprobability sampling method by purpossive sampling had been used to determine the samples' number of this research. The analysis method used was descriptive analysis, partial hypotheses test, coefficient correlations, simple regression and coefficient determination. The results of this research reveals that the use of internal media Portal PT Dirgantara Indonesia has a significant influence on the image of the corporate with a percentage of 70,6%, while the rest of 29,4 % is influenced by factors other than the variables use in this research .Keywords: internal media, public relation, corporate imag

A STUDY ON CHANGES OF DIMENSIONAL PROPERTIES OF GREY KNIT FABRIC DUE TO WET PROCESS

Intension of this work was to find out the changes those occur in knit fabric due to wet-process. To study this four single jersey grey knit fabric samples were taken and the properties courses per cm, wales per cm, stitch density, stitch length, tightness factor and G.S.M. were measured. Then they were subjected to go through a full wet-process cycle which is practiced in knit dyeing factories, i.e.; scouring-bleaching, enzyme process, dyeing, wash-off and finishing with softener were done. The samples were then dried and properties courses per cm, wales per cm, stitch density, stitch length, tightness factor and G.S.M. were measured. Finally they were compared with the properties of their respected grey samples. It is very difficult to predict the properties of a knit fabric before they are produced or received a wetprocess treatment. Which leads to difficulties between two sections namely, the knitting section and the finishing section. The authors hope that this work will increase the understandings between the two section

An Improved Adaptive Filtering Technique to Remove High Density Salt-and-Pepper Noise using Multiple Last Processed Pixels

This paper presents an efficient algorithm which can remove high density salt-and-pepper noise from corrupted digital image This technique differentiates between corrupted and uncorrupted pixels and performs the filtering process only on the corrupted ones The proposed algorithm calculates median only among the noise-free neighborhoods in the processing window and replaces the centre corrupted pixel with that median value The adaptive behavior is enabled here by expanding the processing window based on neighbourhood noise-free pixels In case of high density noise corruption where no noise-free neighborhood is found within the maximum size of window this algorithm takes last processed pixels into the account While most of the existing filtering techniques use only one last processed pixel after reaching maximum window the proposed algorithm considers multiple last processed pixels rather than considering a single one so that more accurate decision can be taken in order to replace the corrupted pixe

A STUDY ON CHANGES OF DIMENSIONAL PROPERTIES OF GREY KNIT FABRIC DUE TO WET PROCESS

Intension of this work was to find out the changes those occur in knit fabric due to wet-process. To study this four single jersey grey knit fabric samples were taken and the properties courses per cm, wales per cm, stitch density, stitch length, tightness factor and G.S.M. were measured. Then they were subjected to go through a full wet-process cycle which is practiced in knit dyeing factories, i.e.; scouring-bleaching, enzyme process, dyeing, wash-off and finishing with softener were done. The samples were then dried and properties courses per cm, wales per cm, stitch density, stitch length, tightness factor and G.S.M. were measured. Finally they were compared with the properties of their respected grey samples. It is very difficult to predict the properties of a knit fabric before they are produced or received a wetprocess treatment. Which leads to difficulties between two sections namely, the knitting section and the finishing section. The authors hope that this work will increase the understandings between the two section

The impact on knowledge spillovers on MNE ownership modes and sub-national locations: Evidence from India

The thesis investigates how FDI intra-industry spillovers are affected by MNE ownership modes and sub-national locations. A conceptual framework is developed which utilises IB theories to propose how MNE ownership modes and sub-national locations are likely to matter for FDI spillovers. The research propositions are explored quantitatively using an unbalanced firm-level panel dataset of 1624 Indian manufacturing firms (1991-2008) with 5203 firm-year observations. The model estimation is carried out in STATA 13.0 in two stages; firstly, by using semi-parametric (Levinsohn-Petrin) method to derive the dependent variable (TFP of domestic firms); and secondly, by using fixed effects model estimated in first-differences to relate TFP of domestic firms' with different measures of foreign presence. Results from the first model reveal that WOSs and MAJVs have positive spillover effects whereas MIJVs have negative spillover effects in the Indian manufacturing sector. The second model finds that the net spillover effect in non-metropolitan regions is higher than in metropolitan regions. The thesis discusses the possible major policy implications of the results and considers possible reasons for the differences in the spillovers for different ownership modes and sub-national locations.PhD Studentship, University of Bradfor

Sub-national locations and FDI spillovers : theory and evidence

The welfare-enhancing role of spillovers from foreign direct investment (FDI) in a host country generates significant interests and debates among policymakers, long after a wide range of regulatory changes in favour of FDI in the late 1980s and the 1990s. The expectation of positive spillovers reinforces the development of government policies to attract multinational enterprises (MNEs) to the host country. However, as is documented in surveys of the literature on FDI spillovers (Görg and Strobl, 2001; Havránek and Irsová, 2012; Meyer and Sinani, 2009; Wooster and Diebel, 2010), the empirical evidence on FDI spillovers is rather mixed. The surveys highlight two important factors that might offer the explanations of mixed findings. First, the degree of foreign ownership is a primary factor in determining the strength of linkages between domestic and foreign firms and thereby affects spillovers (Javorcik and Spatareanu, 2008). As argued by Görg and Greenaway (2004), MNEs may be effective at preventing spillover effects of firm-specific assets. This is connected to the ownership strategies of MNEs that often use wholly owned subsidiaries (WOS) to better control the technologies they transfer to their foreign locations. Second, absorptive capacity of domestic firms and the strength of linkages between domestic and foreign firms are critical for spillovers. However, studies taking these factors into consideration are sparse. According to Havránek and Irsová (2012), among 1205 horizontal spillover estimates from 52 studies, only 5.7 per cent and 7.8 per cent control for absorptive capacity of domestic firms and the strength of linkages between domestic and foreign firms, respectively

PENGARUH KEPUASAN KERJA DAN KOMPETENSI PEGAWAI KESEHATAN TERHADAP KINERJA PEGAWAI RUMAH SAKIT MADANI PEKANBARU

ABSTRAK PENGARUH KEPUASAN KERJA DAN KOMPETENSI PEGAWAI KESEHATAN TERHADAP KINERJA PEGAWAI RUMAH SAKIT MADANI PEKANBARU ZIKO SEPTIANDI Penelitian ini dilakukan di Rumah Sakit Madani Pekanbaru. Tujuan dari penelitian adalah untuk mengetahui pengaruh kepuasan kerja dan kompetensi pegawai kesehatan secara parsial dan simultan terhadap kinerja pegawai Rumah Sakit Madani Pekanbaru. Dengan menggunakan teknik purposive sampling diperoleh sampel penelitian sebanyak 50 orang pegawai rumah sakit yang berprofesi sebagai dokter dan perawat. Data penelitian dikumpulkan melalui kuesioner dan wawancara. Data dianalisis dengan menggunakan teknik analisis deskriptif dan analisis regresi berganda. Hasil penelitian menunjukkan bahwa kepuasan kerja berpengaruh secara parsial terhadap kinerja pegawai. Kompetensi kerja berpengaruh secara parsial terhadap kompetensi pegawai. Secara simultan, kepuasan dan kompetensi kerja berpengaruh terhadap kinerja pegawai Rumah Sakit Madani Pekanbaru. Kata Kunci : Kepuasan kerja, Kompetensi dan Kinerj

Supervised Spectral Subspace Clustering for Visual Dictionary Creation in the Context of Image Classification

International audienceWhen building traditional Bag of Visual Words (BOW) for image classification, the K-means algorithm is usually used on a large set of high dimensional local descriptors to build the visual dictionary. However, it is very likely that, to find a good visual vocabulary, only a sub-part of the descriptor space of each visual word is truly relevant. We propose a novel framework for creating the visual dictionary based on a spectral subspace clustering method instead of the traditional K-means algorithm. A strategy for adding supervised information during the subspace clustering process is formulated to obtain more discriminative visual words. Experimental results on real world image dataset show that the proposed framework for dictionary creation improves the classification accuracy compared to using traditionally built BOW