Cellular and Intraviral Interaction Partners of Papillomavirus E6 Protein

Papillomaviruses are small DNA tumor viruses that infect humans and animals. Persistent infection with high-risk alpha-HPV can develop into cervical and anogenital cancer. HPV16, the most carcinogenic high-risk alpha type, causes >50% of HPV-associated cervical cancers. In addition, cutaneous beta HPV is highly associated with skin cancer in patients with epidermodysplasia verruciformis and individuals with immunosuppression. The carcinogenic E6 and E7 proteins are the major contributors to HPV-associated cancers. They are known to disrupt numerous cellular proteins and signaling pathways essential for tumor suppression. Cottontail rabbit papillomavirus (CRPV) induces papillomas in rabbit skin. It is an established animal model for HPV-mediated carcinogenesis, in which the viral E6 protein plays a critical role. Studies have shown that cutaneous beta-HPV, bovine PV, and mouse PV E6 proteins associate with mastermind-like 1 protein (MAML1) and subsequently inhibit Notch signaling, thereby impairing cell differentiation and proliferation. However, CRPV E6 differs from other E6 proteins in that it encodes an extended E6 protein (long E6, LE6) and an N-terminally truncated product (short E6, SE6). In this work, we describe the interaction between CRPV E6 proteins and MAML1 and their ability to down-regulate Notch signaling, which may be a way CRPV infection induces carcinogenesis similar to beta-HPV. The E6 protein interacts with cellular proteins to disrupt the cellular signaling pathway and can cooperate with E7 proteins to immortalize keratinocytes. The roles of E6 and E7 in the HPV life cycle and the development of carcinogenesis have previously been studied independently. However, a direct interaction between E6 and E7 has yet to be shown. In this thesis, a direct interaction between the E6 and E7 proteins of HPV16 and HPV31 is demonstrated in cell-based assays and verified using biophysical methods. In addition, the involvement of two E7 molecules and two E6 molecules in complex formation was demonstrated by analytical ultracentrifugation. Furthermore, the fluorescence polarization assay showed the binding affinity of the complexes is in a micromolar range. This interaction raises questions about the function of the complex in carcinogenesis and in the viral life cycle that requires further investigation

Targeted drug delivery system:- formulation and evaluation of chitosan nanospheres containing doxorubicin hydrochloride

A chitosan molecule form self-assembled nanoparticles that can encapsulate a quantity of drugs and deliver them to a specific site. Chemical attachment of drug to chitosan throughout the functional linker has possibility to produce useful prodrugs, exhibiting biological activity at target site. In vivo residence time of the dosage form in the gastrointestinal tract and bioavailability of various drugs increases by mucoadhesive and absorption enhancement properties of chitosan. Antitumour activity of doxorubicin(DOX)-incorporated nanoparticles in vitro on DOX- resistant C6 glioma cells. Nanoparticles showed increased cytotoxicity compared to DOX alone. These results suggest that doxorubicin (DOX) was unable to penetrate into cells and did not effectively inhibit cell proliferation. In contrast, nanoparticles can penetrate into cells and effectively inhibit cell proliferation. There are 3 batches of drug loaded nanospheres in which 2.5mg,5mg and 10mg of DOX were loaded into nanospheres where the concentration of chitosan is 1%w/v. Anticancer drugs without targeting a specific site cause side effects. The objective of this research is to reduce side effects. HPLC device was used to quantitatively analyze amount of doxorubicin loaded in nanospheres. The result had showed concentration of anticancer drug loaded in nanospheres is directly proportional to the drug payload capacity until saturation point. The in vitro drug release studies was carried out for 48 hours to obtain a more precise result by carrying out this studies in a medium resembling our body environment such as pH7.4, 37ºC with analytical grade water for this studies. In vitro release of doxorubicin is of zero order kinetic. This shows that release is independent of the concentration of drug loaded in the nanospheres. Besides that, the graphs also show a sustained release manner, indicating these nanospheres formulation are suitable for targeting drug delivery system and for efficient treatment of cancerous cells

Save Environment by Replace Plastic, The Case of PepsiCola

Pepsi-Cola is one of the largest multinational food and beverage brand in the world. In 1902 Pepsi-Cola Company was founded in the United State. It has continuously developed during the past 118 years. Our Report is about replacing Plastic bottle to Reusable Plastic to develop and change the company product to be better. The issue of environmental pollution especially plastic pollution is becoming serious; it is damaging the ecological environment. This had triggered the attention of organization on the environment and some of them take their responsibility to work hard on sustainability a strong environmental profile

ASIC Layout Design-Space Exploration of Pan-and-Tompkins Pre-Processing Algorithm for High Efficiency Electrocardiogram Monitor

Cardiovascular diseases (CVDs) is the leading cause of the death globally. Ambulatory Electrocardiogram (ECG) and mobile monitoring is very important for early heart disease detection and prevention, but its measurement normally contains various types of noise which affect the analysis accuracy. Moreover, long hour ECG monitoring requires an efficient architecture to support real-time processing and low power consumption. This paper presents an application specific integrated circuit (ASIC) design of Pan-and-Tompkins ECG pre-processing algorithm which aims to remove several unwanted noise to increase analysis accuracy. The complete design flow covers high-level algorithm modelling in Matlab, followed by synthesizable design at Register Transfer Level (RTL) until logic synthesis, physical synthesis and static timing analysis to produce VLSI layout. Several power optimization techniques as well as different ASIC process technology libraries in terms of SilTerra’s 180nm CMOS Logic Generic Library (CL180G) and Synopsys 32nm Generic Library (SAED32) are deployed for design-space exploration to study the design trade-off in terms of power consumption, timing performance, and the logic area usage. Results show that the clock gating technique is able to reduce 32.4% of dynamic power in design using CL180G generic library, whereas the integration of several power optimization techniques using SAED32 generic library is able to reduce 43.82% of dynamic power, 91.21% of leakage power and 91.25% of total power

Cannabinoid biosynthesis using non-canonical enzymes

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Targeted drug delivery system:- formulation and evaluation of chitosan nanospheres containing doxorubicin hydrochloride

A chitosan molecule form self-assembled nanoparticles that can encapsulate a quantity of drugs and deliver them to a specific site. Chemical attachment of drug to chitosan throughout the functional linker has possibility to produce useful prodrugs, exhibiting biological activity at target site. In vivo residence time of the dosage form in the gastrointestinal tract and bioavailability of various drugs increases by mucoadhesive and absorption enhancement properties of chitosan. Antitumour activity of doxorubicin(DOX)-incorporated nanoparticles in vitro on DOX- resistant C6 glioma cells. Nanoparticles showed increased cytotoxicity compared to DOX alone. These results suggest that doxorubicin (DOX) was unable to penetrate into cells and did not effectively inhibit cell proliferation. In contrast, nanoparticles can penetrate into cells and effectively inhibit cell proliferation. There are 3 batches of drug loaded nanospheres in which 2.5mg,5mg and 10mg of DOX were loaded into nanospheres where the concentration of chitosan is 1%w/v. Anticancer drugs without targeting a specific site cause side effects. The objective of this research is to reduce side effects. HPLC device was used to quantitatively analyze amount of doxorubicin loaded in nanospheres. The result had showed concentration of anticancer drug loaded in nanospheres is directly proportional to the drug payload capacity until saturation point. The in vitro drug release studies was carried out for 48 hours to obtain a more precise result by carrying out this studies in a medium resembling our body environment such as pH7.4, 37ºC with analytical grade water for this studies. In vitro release of doxorubicin is of zero order kinetic. This shows that release is independent of the concentration of drug loaded in the nanospheres. Besides that, the graphs also show a sustained release manner, indicating these nanospheres formulation are suitable for targeting drug delivery system and for efficient treatment of cancerous cells

Your perception may predict your anxiety level: a preliminary study in primary care in Singapore

Background: Patients’ perception of their medical illness has been shown to associate with not only their responses to the illness but under certain conditions even outcomes of their illness. While anxiety is prevalent among primary care patients, illness perception studies relating to anxiety in this population are scarce. This study aimed to fill this gap and explore clues for perceptual elements of primary care patients’ effective management of their own anxiety. Methods: Ninety-five adult participants (65% female and 35% male) were recruited in two primary care clinics in this cross-sectional study. The questionnaires administered were Generalized Anxiety Disorder-7 (GAD-7) and Illness Perception Questionnaire Mental Health (IPQ-MH) were used to assess anxiety and illness perception respectively. Data analysis was conducted using Spearman’s rho correlation coefficients and linear regression. Results: Four specific dimensions of the participants’ illness perception (i.e., consequences, personal control, coherence and biology) were found to be significantly correlated with their severity of anxiety. In other words, the participants experienced higher anxiety when they perceived a serious impact of anxiety in their lives, experienced a diminished sense of self-efficacy, had trouble understanding their condition and attributed their anxiety to biological causes (which could presumably be ameliorated only with medication). Conclusion: Attribution to biological factors and personal control were highly significant predictors of severity of anxiety. Clinicians should consider psychological interventions that target patients’ medication adherence as well as their physiological responses to anxiety (e.g., breathing skills). Further, anxiety patients’ experience of personal control should be enhanced which could be facilitated through deliberate assessment and reinforcement of the strengths and resources in the patients’ psychosocial spheres

The Associations Between Preoperative Anthropometry and Postoperative Outcomes in Infants Undergoing Congenital Heart Surgery

Aim: We explored the association between preoperative anthropometry and biochemistry, and postoperative outcomes in infants with CHD after cardiac surgery, as infants with congenital heart disease (CHD) often have feeding difficulties and malnutrition. Methodology: This was a retrospective review of infants (≤ 1-year-old) who underwent congenital heart surgery. Preoperative anthropometryin terms of preoperative weight-for-age z-score (WAZ), length-for-age z-score (LAZ), as well as preoperative serum albumin and hemoglobin concentrations, were evaluated against 6-month mortality, and morbidity outcomes including postoperative complications, vasoactive inotrope score, duration of mechanical ventilation, length of stay in the pediatric intensive care unit and in hospital, using the logistic regression or median regression models accounting for infant-level clustering. Results: One hundred and ninety-nine operations were performed in 167 infants. Mean gestational age at birth was 38.0 (SD 2.2) weeks (range 26 to 41 weeks). Thirty (18.0%) infants were born preterm (<37 weeks). The commonest acyanotic and cyanotic lesions were ventricular septal defect (26.3%, 44/167), and tetralogy of Fallot (13.8%, 23/167), respectively. Mean age at cardiac surgery was 94 (SD 95) days. Feeding difficulties, including increased work of breathing during feeding, diaphoresis, choking or coughing during feeding, and inability to complete feeds, was present in 54.3% (108/199) of infants prior to surgery, of which 21.6% (43/199) required tube feeding. The mean preoperative WAZ was−1.31 (SD 1.79). Logistic regression models showed that low preoperative WAZ was associated with increased risk of postoperative complications (odds ratio 1.82; p = 0.02), and 6-month mortality (odds ratio 2.38; p = 0.008) following CHD surgery. There was no meaningful association between the other preoperative variables and other outcomes. Conclusion: More than 50% of infants with CHD undergoing cardiac surgery within the first year of life have feeding difficulties, of which 22% require to be tube-fed. Low preoperative WAZ is associated with increased postoperative complications and 6-month mortality.publishedVersionPeer reviewe

Sustainable Waste-to-Energy Technologies: Bioelectrochemical Systems

The food industry produces a large amount of waste and wastewater, of which most of the constituents are carbohydrates, proteins, lipids, and organic fibers. Therefore food wastes are highly biodegradable and energy rich. Bioelectrochemical systems (BESs) are systems that use microorganisms to biochemically catalyze complex substrates into useful energy products, in which the catalytic reactions take place on electrodes. Microbial fuel cells (MFCs) are a type of bioelectrochemical systems that oxidize substrates and generate electric current. Microbial electrolysis cells (MECs) are another type of bioelectrochemical systems that use an external power source to catalyze the substrate into by-products such as hydrogen gas, methane gas, or hydrogen peroxide. BESs are advantageous due to their ability to achieve a degree of substrate remediation while generating energy. This chapter presents an extensive literature review on the use of MFCs and MECs to remediate and recover energy from food industry waste. These bioelectrochemical systems are still in their infancy state and further research is needed to better understand the systems and optimize their performance. Major challenges and limitations for the use of BESs are summarized and future research needs are identified