Down-regulation of MHC class I by human papillomavirus type 16 E5 protein

Like many viruses, papillomaviruses appear to have evolved mechanisms resulting in escape from host immune surveillance and delay of resolution of infection. The E5 protein is expressed early in papillomavirus infection in the deep layers of the infected epithelium. Human papillomavirus type 16 (HPV-16) E5 is a small protein, 83 amino acids long, and has three hydrophobic domains connected by less hydrophobic regions. It is located mainly at the endosomal membranes, Golgi apparatus (GA) and, to a lesser extent, the plasma membrane. The E5 protein of bovine papillomavirus (BPV) impairs the synthesis and stability of major histocompatibility (MHC) class I complex and prevents their transport to the cell surface due to retention in the GA. The results in this thesis demonstrated that HPV-16 E5 wild type down-regulates surface expression of MHC class I, retains MHC class I complexes in the GA and impedes their transport to the cell surface, which is rescued by treatment with interferon. Unlike BPV E5, HPV-16 E5 does not affect the synthesis of MHC class I heavy chains, and the morphology of the GA. HPV-16 E5 physically interacts with MHC heavy chain in the GA and this interaction is associated with the down-regulation of surface MHC class I. Moreover, we determined that HPV-16 E5 down-regulates selectively HLA-A and B but does not inhibit HLA-C and non-classical HLA-E thus potentially escaping both cytotoxic T lymphocyte (CTL) and natural killer (NK) cells. Deletion mutants of HPV-16 E5 lacking each one of the hydrophobic domains were generated to define its functional domains. HaCaT cells expressing either HPV-16 E5 wild type or its mutants were analysed for their ability to down-regulate surface MHC class I and determine the localization in the cells. All deletion mutants were expressed and localised in the GA. The deletion mutants containing the first hydrophobic domain were all able to down-regulate surface MHC class I, to retain the complex in the GA and interact with MHC heavy chain to extent as HPV-16 E5 wild type. Only the deletion mutant which lacks the first hydrophobic domain was unable to down-regulate surface MHC class I, to retain the complex in the GA and to interact with MHC heavy chain. This study demonstrated that the separate domains of HPV-16 E5 did not have the same function. We found that the first hydrophobic domain of HPV-16 E5 is important for down-regulation of surface MHC class I. Lack of surface MHC class I in infected epithelial cells expressing E5 would allow evasion of CTL killing and thus establishment of viral infection. However, MHC class I down-regulation by E5 is selective, as E5 does not down-regulate HLA-C and non-classical HLA-E. It remains to be seen if E5 expressing cells evade CTL killing, through down-regulation of classical MHC I, and NK killing, through lack of down-regulation of non-classical MHC I

The effects of customer relationship management dimensions on organizational performance (Case study: shipping organization of Iran)

Abstract: Nowadays organizations, for the lack of comprehensive knowledge about the effects of customer's relationship management on the performance, have been failed to expand consistent strategies and the raise of their assets through these relationships. It is obvious about trade expansion in the country and entering into the world market, the relationship management is among the vital needs. Considering the importance of the issue, the present study investigated the effects of customer relationship management on the organizational performance of shipping organization. This was an applicable research in terms of its purpose, and a correlational-survey research in terms of its methodology. The required data were gathered through a questionnaire designed by the re searcher. It contained 40 questions, the validity of which was confirmed with the consideration of experts and supervisor of the study. The reliability, based on Cronbach index, was equal to 0.81. The questionnaire contained questions of personal profile, major and technical questions for studying the stated hypothesis. The collected data were analyzed by SPSS software and at two levels of qualitative (frequency, average, standard deviation) and at inferential level (regre ssion and Freeman nonparametric test). According to the obtained results from regression test, all of the hypotheses of the study were confirmed except the fifteenth hypothesis (the customer relationship management base technology has significant effects on the internal processes performance). The results of the studyshowed that except the mentioned hypothesis, the other dimension of customer relationship management (the organization of customer relationship management, knowledge management, customer orientation, customer relationship management) had significant effects on the organizational performances (financial, customer, internal processes, training and growth). The re sults of Freeman test showed that the studied variables had significant levels of under 0.05. So the ranking of their averages were not equal and the variable of training and expansion had the highest average level. The variable of customer relationship management base on technology had the lowest average in comparison with other variables

The knowledge, attitude, and action of Northern Iranian women about cervical cancer and screening

Background: Cervical cancer is one of the most prevalent cancers in the world among women which its early diagnosis plays an important role in the prognosis. There are many factors that contribute to the participation in the screening programs, most notably the level of knowledge and attitude of people towards cancer. Understanding the level of these factors in the female population and its association with participation in screening programs is important. Therefore, the aim of this study was to determine the knowledge, attitude and practice of women in the north of Iran to compare these factors between two groups with different baseline knowledge.Methods: This cross-sectional study was carried out among female medical clients and healthcare staff in a healthcare center in the north of Iran. All the eligible patients were interviewed and were asked to fill a questionnaire containing the demographic data, knowledge, attitude, and action about cervical cancer and screening. The data were analyzed by SPSS v24.Results: A total of 283 females entered our study of which 156(55.1%) were clients of the healthcare center and 127(44.9%) were non-physician healthcare staff. Ninety (60.8%) of clients and 39(56.5%) of the staff have performed pap smear at least once (p=0.556). The levels of knowledge and attitude were significantly lower in the clients (p < 0.001 and p=0.003, respectively). There were no significant differences regarding the level of knowledge and attitude between those who performed pap smear and those who did not (0.621 and 0.788, respectively).Conclusions: Increasing awareness, especially improving attitudes in the female population, should be the focus of the health care system to encourage more women to participate in screening programs

STABILITY ANALYSIS OF TUNNEL SUPPORT SYSTEMS USING NUMERICAL AND INTELLIGENT SIMULATIONS (CASE STUDY: KOUHIN TUNNEL OF QAZVIN-RASHT RAILWAY)

Izgradnja podzemnih konstrukcija skup je proces, gdje veliku važnost ima procjena i sprječavanje mogućih rizika. Za tu namjenu razvijene su brojne metode, a u radu je prikazana primjena računskoga modela za ocjenu sustava tunela. Prvo je načinjena numerička analiza na temelju metode konačnih razlika (elemenata) uporabom paketa FLAC2D. Njome je modeliran način iskapanja i postavljanja pratećih instalacija. Predviđena masa iskapanja analizirana je s obzirom na osna opterećenja, moment i silu smicanja. Sve te veličine izračunane su za odabrane potporne točke u krovini, središtu, podini te bočnim zidovima. Kako bi se odredila stabilnost sustava, izdvojena su tri klastera i analizirana meta-heurističkim „Bee Colony” algoritmom (u paketu Matlab). Rezultati klasterizacije uspoređeni su s faktorima sigurnosti potpornoga sustava. Pokazali su kako sigurnosne točke klastera 1 imaju manji sigurnosni faktor negoli one u klasterima 2 i 3. Zaključeno je kako model temeljen na algoritmu „Bee Colony” može biti pouzdano primijenjen za početnu procjenu potpornoga sustava tunela, uzimajući u obzir osna i smična naprezanja te moment sile.According to underground construction development and its high cost process, an accurate assessment and prevention of probable risks are of significant importance. Different methods have been developed to assess underground constructions. In this paper, the aim is to develop a new soft computing model to evaluate tunnel support systems. Firstly, a numerical analysis was performed using the explicit finite difference model by FLAC2D software to excavate a sequence model and support system installation. The design loads including the axial force, moment, and shear force were calculated for some important points of the support system including the crown, the middle of the bottom and the side walls. In order to analyse the stability of the support system, the section points were evaluated into 3 clusters by the artificial bee colony as a meta-heuristic algorithm and a k-means algorithm using Matlab software. The results of clustering were compared by the safety factor of the support system. The results indicated that the section points that are in cluster 1 have a lower safety factor than clusters 3 and 2, respectively. It concluded that the artificial bee colony can be reliably used in the initial assessment of tunnel support systems based on the axial force, moment, and shear force

INVESTIGATING THE ROLE OF COOLANT AND LUBRICANT FLUIDS ON THE PERFORMANCE OF CUTTING DISKS (CASE STUDY: HARD ROCKS)

Pravilan odabir rashladnih i mazivih fluida u rezanju tvrdoga arhitektonsko-građevinskog kamena jedan je od najvažnijih čimbenika uspješnosti toga postupka. Također utječe i na veću ekonomičnost pridobivanja te kvalitetu pridobivenoga kamena. Stoga je prikazano istraživanje uloge spomenutih fluida u postupku pripreme takva kamena. Uporabljeno je 10 uzoraka granita prikupljenih u iranskome kamenolomu. Izmjerena su njihova fizička i mehanička svojstva, uključujući jednoosnu tlačnu čvrstoću, tvrdoću prema Mohsovoj ljestvici, faktor trošenja prema Schimazeku te Youngov modul elastičnosti. Uporabljene su tri vrste rashladnih i mazivih tekućina, od kojih su dvije otopine na bazi sapuna u kojima je omjer maziva i hladiva bio 1 : 40 do 1 : 20. Korištene su dvije vrijednosti kojima se određivao način obradbe kamena – stupanj napredovanja i dubina rezanja. Načinjeno je 160 laboratorijskih testiranja za sve omjere fluida te je pri tome mjerena potrošnja električne energije. Rezultati su procijenjeni statistički i drugim algoritmima te su modelirani algoritmom radijalne bazne funkcije. Temeljem rješenja dobivenih objema analitičkim metodama ocijenjeno je kako omjer maziva i praha za rashlađivanje 1 : 20 ima najpovoljniji utjecaj na količinu potrebne električne energije prilikom obradbe kamena.The correct and proper selection of coolant and lubricant fluids in the dimension hard rocks’ cutting process is one of the most important factors in the improvement of the cutting process, and in the increase of economic efficiency and quality of stone production. Therefore, this present study aims to study the role of coolant and lubricant fluids in the cutting performance of dimension hard rocks. In this study, 10 granite stone samples were collected from Iranian quarries and their physical and mechanical properties including their uniaxial compressive strength, Mohs hardness, Schimazek’s F-abrasiveness factors and Young modulus were measured and determined. According to the three types of coolant and lubricant fluids, including the two types of soap water with ratios of 1 to 40 and 1 to 20 and one type of lubricant and coolant powder, and using two different operational parameters such as feed rate (Fr) and depth of cut (Dc), 160 laboratory tests for each of these fluids were studied and measured in order to determine the maximum electrical current consumed by the machine. The obtained results were statistically and intelligently evaluated and analyzed through the radial basis function (RBF). Based upon the results obtained from both the analytical methods, the lubricant and coolant powder with ratios of 1 to 20 had the maximum and minimum effects on the reduction of the maximum consumed electrical current in the hard rocks’ cutting process

Short-term Effects of PM10 to Increase Rate of Hospital Admission Cardiovascular and Respiratory of Sanandaj, Iran During 2015

Sanandaj in the west of Iran is one of the main city that suffered from Arabic Dust Storm (ADS). As Sanandaj isn’t industrial city and located in the mountainous region, one of the main sources of air pollution which has adverse effects on citizens and environment is PM10 which comes from Arabic Dust Storm. In this way, the goal of this study was to the assessment of these adverse health effects. So the hourly data of concentration of PM10 (measured by Beta attenuation method) were taken from Kurdistan Environmental Protection Agency in 2015. the 24-hour average concentration of particulate matter has exceeded about 182 times (days) more than the National Standards and WHO guideline values and the average annual concentration of PM10 were about 1.5 times more than the National Standard and WHO guideline values during the period of the exam. By means of Air Q2,2,3 software the data analyzed and baseline incidence(BI), relative risk(RR) and attributable proportion(AP) were calculated. The results of this study showed that short-term health effect of PM10 could increase of total mortality except accidents and poisoning(4.13%), hospital admission cardiovascular(4.98%), cardiovascular mortality(4.45%), hospital admission respiratory(4.45%) and respiratory mortality(0.2%). This study demonstrated that a high percentage of cardiovascular and respiratory morbidity and mortality rate increased due to the raising of the concentration of PM10. To reduce the emission of PM10 from main sources and relationship between the hospital and Kurdistan Environmental Protection Agency and whether organization and people to be alert are necessary

OCJENA REZIVOSTI STIJENA S LANČANOM SJEKAČICOM PRIMJENOM TEHNIKE PROMATHEE

One of the most significant factors in the estimation of dimension stone quarry cost is the production rate of rock cutting machines. Evaluating the production rate of chain-saw machines is a very significant and practical issue. In this research, it has been attempted to evaluate and select the suitable working-face for a quarry by examining the maximum production rate in the Dehbid and Shayan marble quarries. For this purpose, fi eld studies were carried out which included measuring operational characteristics of the chain-saw cutting machine, the production rate and sampling for laboratory tests from seven active case studies. Subsequently, the physical and mechanical properties of rocks including: Uniaxial Compressive Strength (UCS), Brazilian Tensile Strength (BTS), Los Angeles abrasion, quartz content, water absorption percentage, porosity, Schmidt hardness and grain size for all sample measurements were studied after transferring the samples to a rock-mechanics laboratory. Finally, the sawability of the quarried working-faces was evaluated using the PROMETHEE multi-criteria decision-making (MCDM) model according to the physical and mechanical properties. The results of the study indicated that the number 1 and 5 working-faces from the Dehbid and Shayan quarries are the most suitable working-faces in terms of production rate with the maximum recorded production values (4.95 and 3.1 m2 /h), and with net fl ow rates (2.67 and -0.36) respectively.Jedan od najvažnijih čimbenika u procjeni cijene vađenja građevinskoga kamena jest njegov iznos pridobivanja tijekom strojnoga rezanja. Procjena iznosa proizvodnje takvih strojeva ima vrlo veliku i praktičnu ulogu. Ovdje je načinjena procjena i odabir prikladnoga radilišta unutar kamenoloma radi postizanja najvećega iznosa proizvodnje. Za analizu su odabrani kamenolomi mramora Dehbid i Shayan. Načinjena su terenska ispitivanja, tj. mjerenje operativnih svojstava sjekačice, iznosa pridobivanja te uzorkovanje za laboratorij na sedam smjestišta. Zatim su u laboratoriju za mehaniku stijena izmjerena fizička i mehanička svojstva stijena poput jednoosne kompresijske čvrstoće, brazilske vlačne čvrstoće, abrazije metodom Los Angeles, udjela kvarca, postotka apsorpcije vlage, šupljikavosti, Schmidtove čvrstoće i veličine zrna. Na kraju je ocijenjena rezivost materijala na radilištu kamenoloma uporabom tehnike PROMETHEE, koja predstavlja alat za donošenje odluka na temelju više kriterija koji obuhvaćaju fizička i mehanička svojstva. Rezultati su pokazali kako radilišta označena brojevima 1 i 5, na kamenolomima Dehbid i Shayan, imaju najbolja svojstva postizanja većega brutoiznosa (4,95 i 3,2 m2 /sat) i netoiznosa (2,67 i -0,36 m2 /sat) proizvodnje

T-helper Type 1 and 2 Cytokine Levels in Patients with Benign and Malignant Salivary Gland Tumors

ABSTRACT Background: Salivary gland tumors are among malignancies that have high recurrence rate. Immune responses in salivary gland tumors have not been well elucidated. T helper type 1 (Th1) and Th2 cytokines have been reported to play a role in the outcome of head and neck cancers. Objective: To evaluate the serum levels of interferon gamma (IFN-γ), as the hallmark of Th1 cytokines, and interleukin-4 (IL-4), as the hallmark of Th2 cytokines, in patients with benign and malignant salivary gland tumors in comparison with healthy controls. Methods: Fifty patients with benign and 14 patients with malignant salivary gland tumors, as well as 23 healthy individuals were recruited. Serum levels of IFN-γ and IL-4 were measured using ELISA method. Nonparametric tests were used for data analysis. Results: Serum levels of IFN-γ and IL-4 were found not to be significantly different in patients compared to the control group (0.68 ± 0.29 vs. 1.03 ± 0.57 pg/ml, p=0.58 for IFN-γ, 4.57 ± 1.57 vs. 4.41 ± 1.31 pg/ml, p=0.28 for IL-4). IFN-γ and IL-4 serum levels were also not significantly different between patients with benign and malignant salivary gland tumors (p=0.54 and p=0.86, respectively). Conclusion: The systemic levels of IL-4 and IFN-γ seem not to be associated with salivary gland tumor in our study. Investigation of other cytokines produced by Th1 and Th2 cells are warranted