344 research outputs found
Stability of the Volterra Integrodifferential Equation
In this paper, the Hyers-Ulam stability of the Volterra integrodifferential equation and the Volterra equation on the finite interval [0, T], T > 0, are studied, where the state x(t) take values in a Banach space X
Pyruvate Kinase M2 (PKM2) and Lactate Dehydrogenase A (LDHA) as Novel Diagnostic Markers and Therapeutic Targets for Pancreatic Cancer
Pancreatic cancer is one of the most lethal malignancies worldwide; the early diagnosis of this disease remains challenging and there are few effective therapies, with palliative chemotherapy being the main treatment option for patients with locally advanced or metastatic disease. Alteration of cellular energy metabolism is one of the hallmarks of tumours. Therefore, I proposed that the study of metabolic enzymes such as pyruvate kinase M2 (PKM2) and lactate dehydrogenase A (LDHA), which serve as key regulators of cellular energy metabolism in proliferating cells and mediators of aerobic glycolysis, could play an important role in the diagnosis and therapy of pancreatic cancer. Expression of PKM2 and LDHA was evaluated by immunohistochemistry in pancreatic cancer specimens. I found that the majority of PDAC strongly expressed PKM2 and LDHA at significantly higher levels compared with normal pancreatic tissues and benign pancreatic disease. PKM2 and LDHA expression directly correlated with tumour size and were expressed at higher levels in poorly differentiated tumours compared to well differentiated ones. Tumour cell proliferation, as detected by Ki67 staining, was significantly higher in tumours with strong PKM2 and LDHA expression compared to those with weak PKM2 and LDHA expression. Conversely, the number of CD8+ tumour infiltrating lymphocytes (TILs) was significantly higher in tumours with weak PKM2 and LDHA expression than in those with strong PKM2 and LDHA expression. Patients with tumours that had strong PKM2 and LDHA expression had a significantly worse overall survival compared with those that had weak PKM2 and/or LDHA expression (7.0 months vs. 27.9 months, respectively, p = 0.003, log rank test). Plasma PK and LDH concentrations were also significantly higher in pancreatic cancer patients compared to healthy controls (45.5 vs 21.6 U/L and 685 vs 194 U/L respectively, P < 0.0001). Shikonin (a Chinese herbal medicine) inhibited PKM2 activity and had a strong cytotoxic effect on pancreatic cancer cell proliferation with an IC50 of 2-3µM and 1-2 µM for 24 and 72 hours interaction time, respectively. Treatment of pancreatic cancer cell lines with combination of PKM2 activator IV (TEPP-46) and LDHA inhibitor (FX11) was synergistically inhibited pancreatic cancer cell proliferation, with combination indices (CI) of 0.48 and 0.45 for Miapaca-2 and BxPc-3 cell lines, respectively. Additionally, in the pancreatic cancer xenograft model, TEPP-46 and FX11 in combination significantly delayed both subcutaneous and orthotopic tumour growth compared to the control group (P ˂ 0.0001). The combination treatment also reduced expression of PKM2 and LDHA, and significantly decreased Ki-67 expression compared with controls (P ˂ 0.0001). Orthotopic xenografts treated with the combination therapy had a high number of CD8+TIL cells around the tumours. In conclusion, PKM2 and LDHA overexpression in pancreatic cancer is associated with poor outcome. As such, high expression of these two enzyme may contribute to the aggressiveness of pancreatic cancer and confer anergy against the host anti-tumour immune response. Tetramerisation of PKM2 in combination with inhibition of LDHA synergistically inhibited pancreatic cancer cell proliferation and growth both in vitro and in vivo and may represent a novel strategy for pancreatic cancer therapy
The effect of Levo and Trigard pesticides on the life of potato moth insect Phthorimaea Operculella (Zeller)=Влияние пестицидов Levo и Trigard на смертность картофельной моли Phthorimaea Operculella (Zeller)
The study was conducated in the laboratories of the Department of biogenic control techniques/Technical College/Al-Mussaib for the period from 2015-2016, different concentrations of Levo and Trigar
Pyruvate Kinase M2 and Lactate Dehydrogenase A Are Overexpressed in Pancreatic Cancer and Correlate with Poor Outcome.
Pancreatic cancer has a 5-year survival rate of less than 4%. Despite advances in diagnostic technology, pancreatic cancer continues to be diagnosed at a late and incurable stage. Accurate biomarkers for early diagnosis and to predict treatment response are urgently needed. Since alteration of glucose metabolism is one of the hallmarks of cancer cells, we proposed that pyruvate kinase type M2 (M2PK) and lactate dehydrogenase A (LDHA) enzymes could represent novel diagnostic markers and potential therapeutic targets in pancreatic cancer. In 266 tissue sections from normal pancreas, pancreatic cystic neoplasms, pancreatic intraepithelial neoplasia (PanIN) and cancer, we evaluated the expression of PKM2, LDHA, Ki-67 and CD8+ by immunohistochemistry and correlated these markers with clinicopathological characteristics and patient survival. PKM2 and LDHA expression was also assessed by Western blot in 10 human pancreatic cancer cell lines. PKM2 expression increased progressively from cyst through PanIN to cancer, whereas LDHA was overexpressed throughout the carcinogenic process. All but one cell line showed high expression of both proteins. Patients with strong PKM2 and LDHA expression had significantly worse survival than those with weak PKM2 and/or LDHA expression (7.0 months vs. 27.9 months, respectively, p = 0.003, log rank test). The expression of both PKM2 and LDHA correlated directly with Ki-67 expression, and inversely with intratumoral CD8+ cell count. PKM2 was significantly overexpressed in poorly differentiated tumours and both PKM2 and LDHA were overexpressed in larger tumours. Multivariable analysis showed that combined expression of PKM2 and LDHA was an independent poor prognostic marker for survival. In conclusion, our results demonstrate a high expression pattern of two major glycolytic enzymes during pancreatic carcinogenesis, with increased expression in aggressive tumours and a significant adverse effect on survival
The Effect of Nano Surface Topography on Electrical Properties of Aluminium Films Deposited on Plastic Substrate by Different Technique
Aluminium films have been prepared by two different techniques namely direct current (DC) sputtering and thermal evaporation on polyethylene terephthalate (PET) substrates. Effects of techniques types on the structural and electrical characteristics of the films were studied. The effect of nano surface topography on electrical properties of Aluminium films was studied. Sets of experiments were conducted to optimize the deposition of Aluminium films with appropriate deposition parameters. The deposited films were analyzed with atomic force microscopy and four-point probe technique to determine their structural and electrical characteristics. Film characteristics such as electrical resistivity and surface roughness have been determined
Mechanical characteristics of tire/clay modified epoxy used in fabrication of medical prostheses and artificial human parts
Epoxy is used in many dental and medical applications such as manufacturing prostheses. This polymer is not toxic and is a good candidate for easily forming of artificial hand, leg, etc. In recent years, the recycled waste tire has been concerned as inexpensive modifier for improving the toughness characteristics of many thermoset resins such as epoxy. Herein, the influence of addition of nanoclay on mechanical characteristics of waste tire-modified epoxy was investigated. Mechanical properties i.e. compressive and flexural characteristics, fracture toughness and impact strength of the samples were investigated. The fracture surfaces of the specimens were examined using scanning electron microscope (SEM). Moreover the glass transition temperature (Tg) of the samples were measured. Results reveal that nanoclay can improve the mechanical characteristics of waste tire-modified epoxies. © IDOSI Publications, 2012
An investigation of some biological aspects of three species: tiger toothed croaker, Otolithes ruber, Javelin grunter, Pomadasys kaakan and black pomfret, Parastromateus niger in the Oman Sea for optimizing fishing season
During the years 1382-83, some biological aspects of three species Tiger-toothed Croaker, Otolithes ruber, Javelin grunter, Pomadasys kaakan, Black Pomfret, Parastromateus niger, have been investigated in the Oman Sea along Sistan-O-Baluchistan province. Based on the frequency of developed maturity stages (IV, V), a prologed spawning activity extending from August to March was determined for O.ruber, and the Gonadosomatic Index (GSI) suggests two peaks:the minor one in October and the major one in March-April. Comparison of Hepatosomatic Index (HI) and Condition factor (Kn) with the peak spawning indicated a reverse relationship. According to length at first maturity (Lm50%= 40cm) and exploitation of fish at length 42cm above, the stretched optimum mesh size of nets was calculated to be 100mm. On analysis of stomach food item, fish group dominated (80%), which of them Anchovy accounted for 40% of the total frequency. Comparison of mean length between the years 1374-75 and 1382-83 showed 4cm in decrees. Population dynamics parameters were determined through length based modals and the exploitation rate was estimated to be E=0.6, suggesting high level exploitation. The usal streched mesh size of nets(constructed from multifilament webbing) for capturing O.ruber were less than the proposed optimum mesh size of nets, indicating 78% of the total landings were smaller than Lm50%. Total landings in 1381 have increased up to 15% when compared to those of the year 1376. Despite the decrease of total efforts (Panel.day) by 37%, the mean value CPUE has increased up to 82%. Regarding Pomadasys kaakan species, a year-round spawning activity has been observed, with two peaks: A major one in April and an aminor one in September. As those of O.ruber species, there was an inverse relationship between HI and Kn with the peak spawning activity. Based on the length at first maturity (Lm50% = 44cm) and capturing fish of the length at 46cm and above, the stretched optimum mesh size of nets was calculated to be 149.6mm. According to analysis of stomach contents, fish group accounted for 35% of the groups studied, which of them , Largehead hairtail, Trichiurus lepturus linnaeus, constituted 52% of the total frequency. In addition to estimation of population dynamics, the exploitation rate was estimated to be E= 0.49. Majority of the species catch was made by mesh size of nets used for O.ruber of which 133mm mesh size accounted for the level (30%). Information on length distribution showed that 60% of the total fish landed was below Lm50%. Total landings in 1381 decreased to 10% in comparison to 1376.Total fishing efforts and CPUE also decreased to 33% and 24% respectively. For parastromateus Niger, There was a long period spawning activity from March to December, with two peaks: A major one in August and a minor one in March. According to Lm50% (39cm) and catching of fish 39cm above, the stretched optimum mesh size of nets was calculated as 167.7mm. Based on stomach contents, ring-shaped worms and larval shrimp equally made 29% of the total frequency showing the highest contribution. Comparison of mean length indicated 3cm in decrease in 1382-83 when compared to 1374-75. Population dynamics parameters were estimated and the exploitation rate was estimated to be E = 0.54. The usual stretched mesh size of nets for P. niger was 146mm and 81% of the total fish landed were smaller than Lm50%.In 1381,total catch of the species increased four and a half-fold in comparison to 1376, while total efforts decreased up to 28% and CPUE increased two and a half-fold
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