Search results for: entry inhibitors
385 Synthesis of a Library of Substituted Isoquinolines Based on a Triazolization Strategy, and Their Anti-HIV and C-X-C Chemokine Receptor Type 4 Antagonist Activity
Authors: Mastaneh Safarnejad Shad, Wim Dehaen, Steven De Jonghe
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Since CXCR4 is the main coreceptor of HIV-1 and plays an important role in human immunodeficiency virus (HIV) entry, numerous efforts were directed towards the discovery of new classes of small molecules that act as CXCR4 antagonists. In addition, CXCR4 antagonists are potentially useful in the treatment of several other disorders, such as cancer cell metastasis, leukemia cell proliferation, rheumatoid arthritis, and pulmonary fibrosis. Since AMD3100 (plerixafor) is the only CXCR4 antagonist which obtained approval by the Food and Drug Administration (FDA), we were motivated to investigate a new category of molecules as CXCR4 antagonists. Most of the scaffolds which have been studied so far as CXCR4 antagonists are based on the tetrahydroquinoline (THQ) moiety in which AMD11070 (mavorixafor), GSK-812394, and TIQ15 displayed the most potent CXCR4 antagonism. Due to the high potency of these scaffolds, two different series of compounds were prepared in this work. In the first set, the THQ moiety is coupled to an amine chain and various isoquinoline derivatives (prepared by an in-house developed triazolization strategy), of which the upper part of molecules is identical to AMD11070 and TIQ15. In the second category of compounds, the THQ moiety was simplified by the synthesis of a substituted pyridine moiety. In order to investigate if CXCR4 antagonism requires the presence of an isoquinoline moiety, the corresponding pyridine analogues were also prepared. In both series of compounds, potent CXCR4 antagonism was noticed.Keywords: CXCR4 coreceptor, CXCR4 antagonists, HIV inhibitor, tetrahydroquinoline
Procedia PDF Downloads 193384 Comparing Double-Stranded RNA Uptake Mechanisms in Dipteran and Lepidopteran Cell Lines
Authors: Nazanin Amanat, Alison Tayler, Steve Whyard
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While chemical insecticides effectively control many insect pests, they also harm many non-target species. Double-stranded RNA (dsRNA) pesticides, in contrast, can be designed to target unique gene sequences and thus act in a species-specific manner. DsRNA insecticides do not, however, work equally well for all insects, and for some species that are considered refractory to dsRNA, a primary factor affecting efficacy is the relative ease by which dsRNA can enter a target cell’s cytoplasm. In this study, we are examining how different structured dsRNAs (linear, hairpin, and paperclip) can enter mosquito and lepidopteran cells, as they represent dsRNA-sensitive and refractory species, respectively. To determine how the dsRNAs enter the cells, we are using chemical inhibitors and RNA interference (RNAi)-mediated knockdown of key proteins associated with different endocytosis processes. Understanding how different dsRNAs enter cells will ultimately help in the design of molecules that overcome refractoriness to RNAi or develop resistance to dsRNA-based insecticides. To date, we have conducted chemical inhibitor experiments on both cell lines and have evidence that linear dsRNAs enter the cells using clathrin-mediated endocytosis, while the paperclip dsRNAs (pcRNAs) can enter both species’ cells in a clathrin-independent manner to induce RNAi. An alternative uptake mechanism for the pcRNAs has been tentatively identified, and the outcomes of our RNAi-mediated knockdown experiments, which should provide corroborative evidence of our initial findings, will be discussed.Keywords: dsRNA, RNAi, uptake, insecticides, dipteran, lepidopteran
Procedia PDF Downloads 73383 Evidence Based Policy Studies: Examining Alternative Policy Practice towards Improving Enrolment to Higher Education in Nigeria
Authors: Muftahu Jibirin Salihu, Hazri Jamil
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The persisting challenge of access and enrolment to higher education in commonwealth countries has been reported in several studies, including reports of the international organization such as World Bank, UNESCO among others however from the macro perspective. The overarching aim of this study is to examine alternative policy practices towards improving access to university education in Nigeria at meso level of policy practice from evidence base policy studies using one university as a case. The study adopted a qualitative approach to gain insightful understanding on the issue of the study employing a semi-structure interview and policy documents as the means for obtaining the data and other relevant information for the study. The participants of the study were purposively chosen which comprise of a number of individuals from the selected university and other related organization which responsible for the policies development and implementation of Nigerian higher education system. From the findings of the study, several initiatives have been taken at meso level to address this challenge including the introduction of the University Matriculation Program as an alternative route for enhancing to access to the university education. However, the study further provided a number of recommendations which aimed at improving access to university education such as improving the entry requirements, society orientation on university education and the issue of ranking of certificate among the Nigerian higher institutions of learning.Keywords: policy practice, access, enrolment, university, education, Nigeria
Procedia PDF Downloads 267382 An Observer-Based Direct Adaptive Fuzzy Sliding Control with Adjustable Membership Functions
Authors: Alireza Gholami, Amir H. D. Markazi
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In this paper, an observer-based direct adaptive fuzzy sliding mode (OAFSM) algorithm is proposed. In the proposed algorithm, the zero-input dynamics of the plant could be unknown. The input connection matrix is used to combine the sliding surfaces of individual subsystems, and an adaptive fuzzy algorithm is used to estimate an equivalent sliding mode control input directly. The fuzzy membership functions, which were determined by time consuming try and error processes in previous works, are adjusted by adaptive algorithms. The other advantage of the proposed controller is that the input gain matrix is not limited to be diagonal, i.e. the plant could be over/under actuated provided that controllability and observability are preserved. An observer is constructed to directly estimate the state tracking error, and the nonlinear part of the observer is constructed by an adaptive fuzzy algorithm. The main advantage of the proposed observer is that, the measured outputs is not limited to the first entry of a canonical-form state vector. The closed-loop stability of the proposed method is proved using a Lyapunov-based approach. The proposed method is applied numerically on a multi-link robot manipulator, which verifies the performance of the closed-loop control. Moreover, the performance of the proposed algorithm is compared with some conventional control algorithms.Keywords: adaptive algorithm, fuzzy systems, membership functions, observer
Procedia PDF Downloads 206381 Development and Validation of High-Performance Liquid Chromatography Method for the Determination and Pharmacokinetic Study of Linagliptin in Rat Plasma
Authors: Hoda Mahgoub, Abeer Hanafy
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Linagliptin (LNG) belongs to dipeptidyl-peptidase-4 (DPP-4) inhibitor class. DPP-4 inhibitors represent a new therapeutic approach for the treatment of type 2 diabetes in adults. The aim of this work was to develop and validate an accurate and reproducible HPLC method for the determination of LNG with high sensitivity in rat plasma. The method involved separation of both LNG and pindolol (internal standard) at ambient temperature on a Zorbax Eclipse XDB C18 column and a mobile phase composed of 75% methanol: 25% formic acid 0.1% pH 4.1 at a flow rate of 1.0 mL.min-1. UV detection was performed at 254nm. The method was validated in compliance with ICH guidelines and found to be linear in the range of 5–1000ng.mL-1. The limit of quantification (LOQ) was found to be 5ng.mL-1 based on 100µL of plasma. The variations for intra- and inter-assay precision were less than 10%, and the accuracy values were ranged between 93.3% and 102.5%. The extraction recovery (R%) was more than 83%. The method involved a single extraction step of a very small plasma volume (100µL). The assay was successfully applied to an in-vivo pharmacokinetic study of LNG in rats that were administered a single oral dose of 10mg.kg-1 LNG. The maximum concentration (Cmax) was found to be 927.5 ± 23.9ng.mL-1. The area under the plasma concentration-time curve (AUC0-72) was 18285.02 ± 605.76h.ng.mL-1. In conclusion, the good accuracy and low LOQ of the bioanalytical HPLC method were suitable for monitoring the full pharmacokinetic profile of LNG in rats. The main advantages of the method were the sensitivity, small sample volume, single-step extraction procedure and the short time of analysis.Keywords: HPLC, linagliptin, pharmacokinetic study, rat plasma
Procedia PDF Downloads 241380 The Effectiveness of Spouses' Communication Skills Training on Reducing Emotional Harassment and Adjusting Marital Expectations: Married Iranian Women
Authors: Seyed Ali Kimiaei, Reza Pishghadam, Fatemeh Hajizadeh, Marjan Entezari
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The aim of this study was to investigate the effectiveness of the Minnesota Spouses Communication Skills Program on reducing emotional harassment and adjusting the marital expectations of married women. The research method was quasi-experimental with pretest-posttest design with waiting list group and follow-up period. The statistical population of the study consisted of married women referring to counseling and psychology centers in Mashhad, from which 30 people were selected as a sample by examining the entry criteria and questionnaire scores, and randomly divided into two experimental groups (15 people) and the waiting list group (15 people) were replaced. The experimental group was given 8 sessions of communication skills program of spouses. The emotional harassment and marital expectations questionnaire was used to collect data. The results showed a significant difference between the experimental group and the waiting list group, so that the communication skills training of the spouses reduced emotional harassment and adjusted marital expectations, and these effects continued in the follow-up period. Therefore, we can conclude that teaching the husband's communication skills program in the Minnesota method reduces emotional harassment and modifies women's marital expectations.Keywords: spouses communication skills program, emotional harassment, marital expectations, women
Procedia PDF Downloads 130379 Mitigating the Aggregation of Human Islet Amyloid Polypeptide with Nanomaterials
Authors: Ava Faridi, Pouya Faridi, Aleksandr Kakinen, Ibrahim Javed, Thomas P. Davis, Pu Chun Ke
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Human islet amyloid polypeptide (IAPP) is a hormone associated with glycemic control and type 2 diabetes. Biophysically, the chirality of IAPP fibrils has been little explored with respect to the aggregation and toxicity of the peptide. Biochemically, it remains unclear as for how protein expression in pancreatic beta cells may be altered by cell exposure to the peptide, and how such changes may be mitigated by nanoparticle inhibitors for IAPP aggregation. In this study, we first demonstrated the elimination of the IAPP nucleation phase and shortening of its elongation phase by silica nanoribbons. This accelerated IAPP fibrillization translated to reduced toxicity, especially for the right-handed silica nanoribbons, as revealed by cell viability, helium ion microscopy, as well as zebrafish embryo survival, developmental and behavioral assays. We then examined the proteomes of βTC6 pancreatic beta cells exposed to the three main aggregation states of monomeric, oligomeric and amyloid fibrillar IAPP, and compared that with cellular protein expression modulated by graphene quantum dots (GQDs). A total of 29 proteins were significantly regulated by different forms of IAPP, and the majority of these proteins were nucleotide-binding proteins. A regulatory capacity of GQDs against aberrant protein expression was confirmed. These studies have demonstrated the great potential of employing nanomaterials targeting the mesoscopic enantioselectivity and protein expression dysregulation in pancreatic beta cells.Keywords: graphene quantum dots, IAPP, silica nanoribbons, protein expression, toxicity
Procedia PDF Downloads 142378 Combined Treatment of PARP-1 Inhibitor and Carbon Ion or Gamma Exposure Reduces the Metastatic Potential in Cultured Human Cells
Authors: Priyanka Chowdhury, Asitikantha Sarma, Utpal Ghosh
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Hadron therapy using high Linear Energy Transfer (LET) ion beam is producing promising clinical results worldwide. The major advantages are its ability to kill radio-resistant tumor and its anti-metastatic activity. Poly(ADP-ribose) polymerase-1 (PARP-1) inhibitors have been widely used as radiosensitizer, but its role in metastasis is unknown. The purpose of our study was to investigate the effect of PARP-1 depletion in combination with either Carbon Ion Beam (CIB) or gamma irradiation on metastatic potential of cultured cancerous cells. A549 cells were irradiated with CIB (0-4Gy) or gamma (0, 2, 4, 6 and 10 Gy) with and without PARP-1 inhibition. The metastatic potential of the cells was determined by cell migratory assay, expression, and activity of MMP-2 and MMP-9, expression of Cadherin, Fibronectin, and Vimentin. CIB exposure reduced migratory property and activity of MMP-2 and MMP-9 significantly. CIB with PARP-1 inhibition reduced cell migration and Matrix Metalloproteinase (MMPs) activity in a synergistic manner. Expression of MMPs was also down-regulated in CIB and combined treatment. On the contrary, MMP- 2 and MMP-9 activity was significantly increased in gamma irradiated cells but decreased upon combined treatment of gamma and PARP-1 inhibitor. MMPs expression and migration was reduced when gamma irradiation was combined with PARP-1 inhibition. Thus, our study clearly demonstrates that PARP-1 inhibition in combination with either high or low LET can significantly suppress metastatic potential in cancer cells and thereby can be a promising tool in controlling metastatic cancers.Keywords: high LET, low LET, matrix metalloproteinase (MMP), PARP-1
Procedia PDF Downloads 214377 Management of ASD with Co-morbid OCD: A Literature Review to Compare the Pharmacological and Psychological Treatment Options in Individuals Under the Age of 18
Authors: Gursimran Jandu, Melissa Nelson, Mia Ingram, Hana Jalal
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There is a significant overlap between autism spectrum disorder (ASD) and obsessive-compulsive disorder (OCD), with up to 90% of young people diagnosed with ASD having this co-morbidity. Distinguishing between the symptoms of the two leads to issues with accurate treatment, yet this is paramount in benefiting the young person. There are two distinct methods of treatment, psychological or pharmacological, with clinicians tending to choose one or the other, potentially due to the lack of research available. This report reviews the efficacy of psychological and pharmacological treatments for young people diagnosed with ASD and co-morbid OCD. A literature review was performed on papers from the last fifteen years including ‘ASD’, ‘OCD’ and individuals under the age of 18. Eleven papers were selected as relevant. The report looks at the comparison between more traditional methods, such as selective-serotonin-reuptake-inhibitors (SSRI) and Cognitive behaviour therapy (CBT), and newer therapies, such as modified or intensive ASD focused psychotherapies, and the use of other medication classes. On reviewing the data, it was identified that there was a distinct lack of information on this important topic. The most widely used treatment was medication such as Fluoxetine, an SSRI, which rarely showed improvement in symptoms or outcomes. This is in contrast to modified forms of CBT which often reduces symptoms or even results in OCD remission. With increased research into non-traditional management of these co-morbid conditions, it is clear there is scope that modified CBT may become the future treatment of choice for OCD in young people with ASD.Keywords: autism spectrum disorder, intensive or adapted cognitive behavioural therapy, obsessive compulsive disorder, pharmacological management
Procedia PDF Downloads 9376 Crude Extracts of Medicinal Plants Can Inhibit Some Bacteria of Clinical Importance in Minced Meat
Authors: Chika C. Ogueke, Ijeoma M. Agunwah
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The antimicrobial activities and preservative potentials of crude extracts of Alstonia boonei stem bark and Euphorbia hirta leaves were studied. Soxhlet extraction and cold ethanol extraction methods were used for the extraction of the dried and ground plant samples. Well in agar diffusion method was used for the antimicrobial screening at different concentrations of 25mg/ml, 50mg/ml, 100mg/ml and 200mg/ml on E.coli and B.subtilis. The preservative effects of the extracts at 0.1%, 0.2% and 0.3% singly and in combination were determined in minced meat using E. coli and B. subtilis as test isolates. Phytochemical analysis was also conducted on the extracts using standard analytical methods. E.hirta cold and A.boonei cold extracts gave the highest zone of growth inhibition on E. coli and B.substilis with 20mm zone diameter at 200mg/ml concentration. Phytochemical analysis revealed the presence of alkaloids, flavonoids, tannins, saponins and cardiac glycosides. A.boonei at 0.1, 0.2 and 0.3% produced a log cycle reduction on the growth of E.coli. Mixture of A. boonei and E. hirta extracts (1:1) at 0.1% and 0.2% also produced a log cycle reduction on the growth of E.coli and B. subtilis, however the A. boonei extracts had more significant effect on the isolates. The observed antimicrobial activities are attributed to the phytochemicals identified in the extracts. The results reveal the potentials of plant extracts as natural antimicrobial preservatives in minced meat. Thus the crude extracts can act as inhibitors of bacteria in a food system. Upon further purification better results may be obtained.Keywords: antimicrobial preservative, crude extracts, minced meat, test isolates
Procedia PDF Downloads 293375 Vascular Foramina of the Capitate Bone of the Hand – an Anatomical Study
Authors: Latha V. Prabhu, B.V. Murlimanju, P.J. Jiji, Mangala M. Pai
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Background: The capitate is the largest among the carpal bones. There exists no literature about the vascular foramina of the capitate bone. The objective of the present study was to investigate the morphology and number of the nutrient foramina in the cadaveric dried capitate bones of the Indian population. Methods: The present study included 59 capitate bones (25 right sided and 34 left sided) which were obtained from the gross anatomy laboratory of our institution. The bones were macroscopically observed for the nutrient foramina and the data was collected with respect to their number. The tabulation of the data and analysis were done. Results: All of our specimens (100%) exhibited the nutrient foramina over the non-articular and articular surfaces. The foramina were observed at the medial, lateral, palmar and dorsal surfaces of the capitate bones. The foramina were ranged from 6 to 23 in each capitate bone. In the medial surface, the foramina ranged from 1 to 6, lateral surface from 0 to 7, the foramina ranged between 0 and 5 in the palmar surface. However most of the foramina were located at the dorsal surface which ranged from 3 to 11. Conclusion: We believe that the present study has provided additional data about the nutrient foramina of the capitate bones. The data is enlightening to the orthopedic surgeon and would help in the hand surgeries. The knowledge about the foramina is also important to the radiologists to prevent the misinterpretation of the findings in the x ray and computed tomogram scan films. The foramina may mimick like erosions and ossicles. The morphological knowledge of the vasculature, their foramina of entry and number is required to understand the concepts in the avascular necrosis of the capitate.Keywords: avascular necrosis, capitate, morphology, nutrient foramen
Procedia PDF Downloads 344374 Conceptualizing Place Attachment Affordance
Authors: Priya Narayanan
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Despite several studies having been conducted on the highly subjective concept of place attachment in the last 60 years, there is a lack of consensus among researchers about how it can be measured empirically. Further, there is no available literature that discusses how a place can be manipulated via design and/or policy to allow people to feel/get attached to it, an aspect that seems to be the need of the hour in a world where a substantial population is living in shelter homes as war/climate/social refugees. Consequently, this paper draws from studies on place, affordance and attachment to conceptualize an objectively measurable entity in place attachment affordance by asking ‘whether and to what degree a place allows one to form attachment bonds with it’ rather than the generally asked ‘whether and to what degree one is/feels attached to a place’. Towards this, the place attachment affordance scale (PAAS) has been developed to not only quantitatively measure place attachment affordance but also act as a point of entry into a more in-depth analysis of both place policy and place properties. To illustrate the validity of the scale, the study uses PAAS to compare shelter homes for women in crisis with the homes they once lived in to glean the degree to which both places afford the formation of place attachment bonds to the residents. PAAS has also been used to compare shelter homes as places of short-/long-term residence for the residents and as places of work for the staff. Based on the results, it is suggested that place attachment and built environment researchers employ the PAAS as an objective measurement tool to better understand not only the presence or absence of attachment bonds with place but also the attributes of place that encourage or discourage the same. The study also briefly discusses the universality of the PAAS, although further fieldwork might be required to substantiate the same.Keywords: place attachment, affordance, shelter homes, home, scale, environmental psychology
Procedia PDF Downloads 29373 Role of Special Training Centers (STC) in Right to Education Act Challenges And Remedies
Authors: Anshu Radha Aggarwal
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As per the Right to Education Act (RTE), 2009, every child in the age group of 6-14 years shall be admitted in a neighborhood school. All the Out of School Children identified have to be enrolled / mainstreamed in to age appropriate class and there-after be provided special training. This paper addresses issues emerging from provisions in the RTE Act that specifically refer to the enrolment of out-of school children into age appropriate classes and the requirement to provide special trainings that will enable this to take place. In the context of RTE Act, the Out-of-School Children are first enrolled in the formal school and then they are provided with Special Training through NRSTCs (Long Term / Short term basis). These centers are functioning in formal school campus itself. This paper specifies the role of special training centers (STC). It presents a re-envisioning of assessment that recognizes two principal functions of assessment, assessment for learning and assessment of learning, instead of the more familiar categories of formative, diagnostic, summative, and evaluative assessment. The use of these two functions of assessment highlights and emphasizes the role of special training centers (STC) to assess their level for giving them appropriate special training and to evaluate their improvement in learning level. Challenge of problem faced by teachers to do diagnostic assessment, including its place in the sequence of assessment procedures appropriate in identifying and addressing individual children’s learning difficulties are solved by special training centers (STC). It is important that assessment is used to identify children with learning difficulties at the earliest possible stage so that appropriate support and intervention can be put in place. So appropriate challenges with tools are presented here for their assessment at entry level and at completion level of primary children by special training centers (STC).Keywords: right to education, assessment, challenges, out of school children
Procedia PDF Downloads 461372 Monthly Labor Forces Surveys Portray Smooth Labor Markets and Bias Fixed Effects Estimation: Evidence from Israel’s Transition from Quarterly to Monthly Surveys
Authors: Haggay Etkes
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This study provides evidence for the impact of monthly interviews conducted for the Israeli Labor Force Surveys (LFSs) on estimated flows between labor force (LF) statuses and on coefficients in fixed-effects estimations. The study uses the natural experiment of parallel interviews for the quarterly and the monthly LFSs in Israel in 2011 for demonstrating that the Labor Force Participation (LFP) rate of Jewish persons who participated in the monthly LFS increased between interviews, while in the quarterly LFS it decreased. Interestingly, the estimated impact on the LFP rate of self-reporting individuals is 2.6–3.5 percentage points while the impact on the LFP rate of individuals whose data was reported by another member of their household (a proxy), is lower and statistically insignificant. The relative increase of the LFP rate in the monthly survey is a result of a lower rate of exit from the LF and a somewhat higher rate of entry into the LF relative to these flows in the quarterly survey. These differing flows have a bearing on labor search models as the monthly survey portrays a labor market with less friction and a “steady state” LFP rate that is 5.9 percentage points higher than the quarterly survey. The study also demonstrates that monthly interviews affect a specific group (45–64 year-olds); thus the sign of coefficient of age as an explanatory variable in fixed-effects regressions on LFP is negative in the monthly survey and positive in the quarterly survey.Keywords: measurement error, surveys, search, LFSs
Procedia PDF Downloads 270371 Liver Histopathological Findings after Treatment with Anastrazole and Letrozole in Ovariectomized Rats
Authors: Ioannis Boutas, Vasilios Pergialiotis, Nicolaos Salakos, George Agrogiannis, Panagiotis Konstantopoulos, Laskarina-Maria Korou, Theodoros Kalampokas, Odysseas Gregoriou, George Creatsas, Despina Perrea
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Introduction: The effect of third generation aromatase inhibitors in the lipid profile among women with breast cancer, present diversities. It has been also shown that low levels of estrogens affect liver metabolism in mice in numerous ways, such as lipid accumulation and hepatic steatosis. Materials and Methods: Forty-five female Wistar rats underwent surgical ovariectomy. The animals were anesthetized with a combination of ketamine (75 mg/kg) and xylazine (10 mg/kg) which were administered intraperitoneally. After the ovariectomy, the operated animals were randomized in three groups. The first group did not receive any drug regimen (ovariectomized control group). The second group received Anastrazole and the third group received Letrozole. Four months after the initiation of the study, the animals were euthanized and livers were dissected immediately for further histopathological analysis. The histological features were grouped into 4 broad categories: steatosis, ballooning, portal inflammation and lobular activity. A score from 0 (absence) to 3 (severe) was assigned to each parameter. Results: The liver pathology analysis revealed significant differences among groups with favored mild steatosis and ballooning among animals that received Anastrazole or Letrozole. Conclusion: The effect of Anastrazole and Letrozole on liver function have not yet been clarified. In our study mild histological liver alterations seem also to occur and these alterations should be taken in mind in future clinical studiesKeywords: anastrazole, letrozole, liver, rats
Procedia PDF Downloads 352370 Anticancer Activity of Calyx of Diospyros kaki Thunb. through Downregulation of Cyclin D1 Protein Level in Human Colorectal Cancer Cells
Authors: Jin Boo Jeong
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In this study, we elucidated anti-cancer activity and potential molecular mechanism of DKC against human colorectal cancer cells. DKC-E70 suppressed the proliferation of human colorectal cancer cell lines such as HCT116, SW480, LoVo and HT-29. Although DKC-E70 decreased cyclin D1 expression in protein and mRNA level, decreased level of cyclin D1 protein by DKC-E70 occurred at the earlier time than that of cyclin D1 mRNA, which indicates that DKC-E70-mediated downregulation of cyclin D1 protein may be a consequence of the induction of degradation and transcriptional inhibition of cyclin D1. In cyclin D1 degradation, we found that cyclin D1 downregulation by DKC-E70 was attenuated in presence of MG132. In addition, DKC-E70 phosphorylated threonine-286 (T286) of cyclin D1 and T286A abolished cyclin D1 downregulation by DKC-E70. We also observed that DKC-E70-mediated T286 phosphorylation and subsequent cyclin D1 degradation was blocked in presence of the inhibitors of ERK1/2, p38 or GSK3β. In cyclin D1 transcriptional inhibition, DKC-E70 inhibited the expression of β-catenin and TCF4, and β–catenin/TCF-dependent luciferase activity. Our results suggest that DKC-E70 may downregulate cyclin D1 as one of the potential anti-cancer targets through cyclin D1 degradation by T286 phosphorylation dependent on ERK1/2, p38 or GSK3β, and cyclin D1 transcriptional inhibition through Wnt signaling. From these findings, DKC-E70 has potential to be a candidate for the development of chemoprevention or therapeutic agents for human colorectal cancer. This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (NRF-2016R1D1A3B03931713).Keywords: anticancer, calyx of persimmon, cyclin D1, Diospyros kaki Thunb., human colorectal cancer
Procedia PDF Downloads 312369 Micro- and Nanoparticle Transport and Deposition in Elliptic Obstructed Channels by Lattice Boltzmann Method
Authors: Salman Piri
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In this study, a two-dimensional lattice Boltzmann method (LBM) was considered for the numerical simulation of fluid flow in a channel. Also, the Lagrangian method was used for particle tracking in one-way coupling. Three hundred spherical particles with specific diameters were released in the channel entry and an elliptical object was placed in the channel for flow obstruction. The effect of gravity, the drag force, the Saffman lift and the Brownian forces were evaluated in the particle motion trajectories. Also, the effect of the geometrical parameter, ellipse aspect ratio, and the flow characteristic or Reynolds number was surveyed for the transport and deposition of particles. Moreover, the influence of particle diameter between 0.01 and 10 µm was investigated. Results indicated that in small Reynolds, more inertial and gravitational trapping occurred on the obstacle surface for particles with larger diameters. Whereas, for nano-particles, influenced by Brownian diffusion and vortices behind the obstacle, the inertial and gravitational mechanisms were insignificant and diffusion was the dominant deposition mechanism. In addition, in Reynolds numbers larger than 400, there was no significant difference between the deposition of finer and larger particles. Also, in higher aspect ratios of the ellipse, more inertial trapping occurred for particles of larger diameter (10 micrometers), while in lower cases, interception and gravitational mechanisms were dominant.Keywords: ellipse aspect elito, particle tracking diffusion, lattice boltzman method, larangain particle tracking
Procedia PDF Downloads 79368 Management of ASD with Co-Morbid OCD: A Literature Review to Compare the Pharmacological and Psychological Treatment Options in Individuals Under the Age of 18
Authors: Melissa Nelson, Simran Jandu, Hana Jalal, Mia Ingram, Chrysi Stefanidou
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There is a significant overlap between autism spectrum disorder (ASD) and obsessive compulsive disorder (OCD), with up to 90% of young people diagnosed with ASD having this co-morbidity. Distinguishing between the symptoms of the two leads to issues with accurate treatment, yet this is paramount in benefitting the young person. There are two distinct methods of treatment, psychological or pharmacological, with clinicians tending to choose one or the other, potentially due to the lack of research available. This report reviews the efficacy of psychological and pharmacological treatments for young people diagnosed with ASD and co-morbid OCD. A literature review was performed on papers from the last fifteen years, including “ASD,” “OCD,” and individuals under the age of 18. Eleven papers were selected as relevant. The report looks at the comparison between more traditional methods, such as selective serotonin reuptake inhibitors (SSRI) and cognitive behavior therapy (CBT), and newer therapies, such as modified or intensive ASD-focused psychotherapies and the use of other medication classes. On reviewing the data, it was identified that there was a distinct lack of information on this important topic. The most widely used treatment was medication such as Fluoxetine, an SSRI, which rarely showed an improvement in symptoms or outcomes. This is in contrast to modified forms of CBT, which often reduces symptoms or even results in OCD remission. With increased research into the non-traditional management of these co-morbid conditions, it is clear there is scope that modified CBT may become the future treatment of choice for OCD in young people with ASD.Keywords: autism spectrum disorder, intensive or adapted cognitive behavioral therapy, obsessive compulsive disorder, pharmacological management
Procedia PDF Downloads 9367 Thermochemical Study of the Degradation of the Panels of Wings in a Space Shuttle by Utilization of HSC Chemistry Software and Its Database
Authors: Ahmed Ait Hou
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The wing leading edge and nose cone of the space shuttle are fabricated from a reinforced carbon/carbon material. This material attains its durability from a diffusion coating of silicon carbide (SiC) and a glass sealant. During re-entry into the atmosphere, this material is subject to an oxidizing high-temperature environment. The use of thermochemical calculations resulting at the HSC CHEMISTRY software and its database allows us to interpret the phenomena of oxidation and chloridation observed on the wing leading edge and nose cone of the space shuttle during its mission in space. First study is the monitoring of the oxidation reaction of SiC. It has been demonstrated that thermal oxidation of the SiC gives the two compounds SiO₂(s) and CO(g). In the extreme conditions of very low oxygen partial pressures and high temperatures, there is a reaction between SiC and SiO₂, leading to SiO(g) and CO(g). We had represented the phase stability diagram of Si-C-O system calculated by the use of the HSC Chemistry at 1300°C. The principal characteristic of this diagram of predominance is the line of SiC + SiO₂ coexistence. Second study is the monitoring of the chloridation reaction of SiC. The other problem encountered in addition to oxidation is the phenomenon of chloridation due to the presence of NaCl. Indeed, after many missions, the leading edge wing surfaces have exhibited small pinholes. We have used the HSC Chemistry database to analyze these various reactions. Our calculations concorde with the phenomena we announced in research work resulting in NASA LEWIS Research center.Keywords: thermochchemicals calculations, HSC software, oxidation and chloridation, wings in space
Procedia PDF Downloads 124366 Comparative Study between Angiotensin Converting Enzyme Inhibitors and Angiotensin Receptor Blockers on Ulcerative Colitis Induced Experimentally in Rats
Authors: Azza H. El-Medany, Hanan H. Hagar, Jamila H. El-Medany
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Ulcerative colitis (UC) is one of chronic inflammatory diseases primarily affecting colon with unknown etiology. Some researches papers mentioned the possibility of the use of drugs that affect the angiotensin II in reducing the complication of ulcerative colitis. The aim of the present study is to evaluate the potential protective and therapeutic effects of captopril and valsartan on ulcerative colitis induced experimentally in rats using acetic acid. The results were assessed by histological assessment of colonic tissues and measurement of malondialdehyde (MDA), tumor necrosis factor (TNF-α), transforming growth factor (TGF-1B), angiotensin converting enzyme (ACE), reduced glutathione (GSH) and platelet activating factor (PAF) levels in colonic tissues. Oral pre-treatment with captopril or valsartan in a dose of 30 mgkg-1 body weight for 2 weeks before induction of colitis (prophylactic groups) and continuously for 2 weeks after induction (therapeutic groups) significantly reduce MDA, TNF-α, PAF, TGF-1B and ACE levels in colonic tissues as compared to acetic acid control group. Also, a significant increase in GSH level was observed in colonic tissues. Captopril and valsartan attenuated the macroscopic and microscopic colonic damage induced by acetic acid. These results suggest that either captopril or valsartan may be effective as prophylactic or treatment of UC through inhibition of ACE and scavenging effect on oxygen-derived free radicals.Keywords: captopril, valsartan, angiotensin converting enzyme, reduced glutathione, tumor necrosis factor
Procedia PDF Downloads 269365 A Project Screening System for Energy Enterprise Based on Dempster-Shafer Theory
Authors: Woosik Jang, Seung Heon Han, Seung Won Baek
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Natural gas (NG) is an energy resource in a few countries, and most NG producers do business in politically unstable countries. In addition, as 90% of the LNG market is controlled by a small number of international oil companies (IOCs) and national oil companies (NOCs), entry of latecomers into the market is extremely limited. To meet these challenges, project viability needs to be assessed based on limited information from a project screening perspective. However, the early stages of the project have the following difficulties: (1) What are the factors to consider? (2) How many professionals do you need to decide? (3) How to make the best decision with limited information? To address this problem, this study proposes a model for evaluating LNG project viability based on the Dempster-Shafer theory (DST). A total of 11 indicators for analyzing the gas field, reflecting the characteristics of the LNG industry, and 23 indicators for analyzing the market environment, were identified. The proposed model also evaluates the LNG project based on the survey and provides uncertainty of the results based on DST as well as quantified results. Thus, the proposed model is expected to be able to support the decision-making process of the gas field project using quantitative results as a systematic framework, and it was developed as a stand-alone system to improve its usefulness in practice. Consequently, the amount of information and the mathematical approach are expected to improve the quality and opportunity of decision making for LNG projects for enterprises.Keywords: project screen, energy enterprise, decision support system, Dempster-Shafer theory
Procedia PDF Downloads 341364 Post Injury Experiences of New Immigrant Workers
Authors: Janki Shankar, Shu Ping Chen
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Background: New immigrants are one of most vulnerable sections of the Canadian society. Unable to gain entry into Canada’s strictly regulated professions and trades, several skilled and qualified new immigrants take up precarious jobs without adequate occupational health and safety training, thereby increasing their risk of sustaining occupational injury and illness compared to Canadian born workers. Access to timely and appropriate support is critical for injured new immigrant workers who face additional challenges compared to Canadian born workers in accessing information and support post-injury. The purpose of our study was to explore the post-injury experiences and support needs of new immigrant workers who have sustained work-related injuries. Methods: Using an interpretive research approach and semi structured face to face qualitative interviews, 27 new immigrant workers from a range of industries operating in two cities in a province in Canada were interviewed. All had sustained work-related injuries and reported these to their work supervisors. A constant comparative approach was used to identify key themes across the worker experiences. Results: Findings reveal several factors that can shape the experiences of new immigrant workers and influence their return-to-work outcomes. Conclusion: Based on the insights of study participants, policies, practices, and potential interventions informed by their needs and preferences are proposed that can improve return to work outcomes for these workers.Keywords: new immigrant workers, post-injury experiences, return to work outcomes, qualified
Procedia PDF Downloads 101363 Computational Fluid Dynamics Simulation of Reservoir for Dwell Time Prediction
Authors: Nitin Dewangan, Nitin Kattula, Megha Anawat
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Hydraulic reservoir is the key component in the mobile construction vehicles; most of the off-road earth moving construction machinery requires bigger side hydraulic reservoirs. Their reservoir construction is very much non-uniform and designers used such design to utilize the space available under the vehicle. There is no way to find out the space utilization of the reservoir by oil and validity of design except virtual simulation. Computational fluid dynamics (CFD) helps to predict the reservoir space utilization by vortex mapping, path line plots and dwell time prediction to make sure the design is valid and efficient for the vehicle. The dwell time acceptance criteria for effective reservoir design is 15 seconds. The paper will describe the hydraulic reservoir simulation which is carried out using CFD tool acuSolve using automated mesh strategy. The free surface flow and moving reference mesh is used to define the oil flow level inside the reservoir. The first baseline design is not able to meet the acceptance criteria, i.e., dwell time below 15 seconds because the oil entry and exit ports were very close. CFD is used to redefine the port locations for the reservoir so that oil dwell time increases in the reservoir. CFD also proposed baffle design the effective space utilization. The final design proposed through CFD analysis is used for physical validation on the machine.Keywords: reservoir, turbulence model, transient model, level set, free-surface flow, moving frame of reference
Procedia PDF Downloads 152362 High Titer Cellulosic Ethanol Production Achieved by Fed-Batch Prehydrolysis Simultaneous Enzymatic Saccharification and Fermentation of Sulfite Pretreated Softwood
Authors: Chengyu Dong, Shao-Yuan Leu
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Cellulosic ethanol production from lignocellulosic biomass can reduce our reliance on fossil fuel, mitigate climate change, and stimulate rural economic development. The relative low ethanol production (60 g/L) limits the economic viable of lignocellulose-based biorefinery. The ethanol production can be increased up to 80 g/L by removing nearly all the non-cellulosic materials, while the capital of the pretreatment process increased significantly. In this study, a fed-batch prehydrolysis simultaneously saccharification and fermentation process (PSSF) was designed to converse the sulfite pretreated softwood (~30% residual lignin) to high concentrations of ethanol (80 g/L). The liquefaction time of hydrolysis process was shortened down to 24 h by employing the fed-batch strategy. Washing out the spent liquor with water could eliminate the inhibition of the pretreatment spent liquor. However, the ethanol yield of lignocellulose was reduced as the fermentable sugars were also lost during the process. Fed-batch prehydrolyzing the while slurry (i.e. liquid plus solid fraction) pretreated softwood for 24 h followed by simultaneously saccharification and fermentation process at 28 °C can generate 80 g/L ethanol production. Fed-batch strategy is very effectively to eliminate the “solid effect” of the high gravity saccharification, so concentrating the cellulose to nearly 90% by the pretreatment process is not a necessary step to get high ethanol production. Detoxification of the pretreatment spent liquor caused the loss of sugar and reduced the ethanol yield consequently. The tolerance of yeast to inhibitors was better at 28 °C, therefore, reducing the temperature of the following fermentation process is a simple and valid method to produce high ethanol production.Keywords: cellulosic ethanol, sulfite pretreatment, Fed batch PSSF, temperature
Procedia PDF Downloads 367361 Human Immunodeficiency Virus (HIV) Test Predictive Modeling and Identify Determinants of HIV Testing for People with Age above Fourteen Years in Ethiopia Using Data Mining Techniques: EDHS 2011
Authors: S. Abera, T. Gidey, W. Terefe
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Introduction: Testing for HIV is the key entry point to HIV prevention, treatment, and care and support services. Hence, predictive data mining techniques can greatly benefit to analyze and discover new patterns from huge datasets like that of EDHS 2011 data. Objectives: The objective of this study is to build a predictive modeling for HIV testing and identify determinants of HIV testing for adults with age above fourteen years using data mining techniques. Methods: Cross-Industry Standard Process for Data Mining (CRISP-DM) was used to predict the model for HIV testing and explore association rules between HIV testing and the selected attributes among adult Ethiopians. Decision tree, Naïve-Bayes, logistic regression and artificial neural networks of data mining techniques were used to build the predictive models. Results: The target dataset contained 30,625 study participants; of which 16, 515 (53.9%) were women. Nearly two-fifth; 17,719 (58%), have never been tested for HIV while the rest 12,906 (42%) had been tested. Ethiopians with higher wealth index, higher educational level, belonging 20 to 29 years old, having no stigmatizing attitude towards HIV positive person, urban residents, having HIV related knowledge, information about family planning on mass media and knowing a place where to get testing for HIV showed an increased patterns with respect to HIV testing. Conclusion and Recommendation: Public health interventions should consider the identified determinants to promote people to get testing for HIV.Keywords: data mining, HIV, testing, ethiopia
Procedia PDF Downloads 496360 Effects of Concentrator and Encapsulated Phase Change Material for Desalination: An Experimental Study
Authors: Arunkumar Thirugnanasambantham, Velraj Ramalingam
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An experimental attempt has been made to study the effect of system integration by two different concentrator assisted desalting systems. The compound parabolic concentrator (CPC) and compound conical concentrator (CCC) are used in this research work. Two solar desalination systems, the single slope solar still (SSSS) and pyramid solar still (PSS), have been integrated with a CCC and compound parabolic concentrator-concentric circular tubular solar still (CPC-CCTSS). To study the effect of system integration, a thick cloth prevents the entry of sunlight into the solar still top. Additionally, the concentrator assisted desalting systems are equipped with phase change material (PCM) for enhancement. In CCC-SSSS, PCM has been filled inside copper balls and placed on the SSSS basin. The PCM is loaded in the specially designed circular trough of the tubular solar still. Here, the used concentrators and distillers are not the same. Two methodologies are followed here to produce the fresh water even while the distillers are blocked from the sunlight. They are (1) thermosyphon effect in CCC-SSSS and (2) waste heat recovery from CPC-CCTSS. The results showed that the productivity of CCC-SSSS, CCC-SSSS with PCM and CCC-SSSS (PCM) top cover shaded were found as 2680 ml / m² / day, 3240 ml / m² / day, and 1646 ml / m² / day. Similarly, the productivity of the CPC-CCTSS-PSS, CPC-CCTSS (PCM)-PSS and CPC-CCTSS (PCM)-PSS top cover shaded were found as 7160 ml / m² / day, 7346 ml / m² / day, and ml / m² / day. The productivity of the CCC-SSSS and CPC-CCTSS-PSS is examined, and conclusions are drawn such as the solar radiation blocked distillers productivity did not drop to zero.Keywords: compound conical concentrator, compound parabolic concentrator, desalination, system integration
Procedia PDF Downloads 261359 Horizontal Bone Augmentation Using Two Membranes at Dehisced Implant Sites: A Randomized Clinical Study
Authors: Monika Bansal
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Background: Placement of dental implant in narrow alveolar ridge is challenging to be treated. GBR procedure is currently most widely used to augment the deficient alveolar ridges and to treat the fenestration and dehiscence around dental implants. Thus, the objectives of the present study were to evaluate as well as compare the clinical performance of collagen membrane and titanium mesh for horizontal bone augmentation at dehisced implant sites. Methods and material: Total 12 single edentulous implant sites with buccal bone deficiency in 8 subjects were equally divided and treated simultaneously with either of the two membranes and DBBM(Bio-Oss) bone graft. Primary outcome measurements in terms of defect height and defect width were made using a calibrated plastic periodontal probe. Re-entry surgery was performed to remeasure the augmented site and to remove Ti-mesh at 6th month. Independent paired t-tests for the inter-group comparison and student-paired t-tests for the intra-group comparison were performed. The differences were considered to be significant at p ≤ 0.05. Results: Mean defect fill with respect to height and width was 3.50 ± 0.54 mm (87%) and 2.33 ± 0.51 mm (82%) for collagen membrane and 3.83 ± 0.75 mm (92%) and 2.50 ± 0.54 mm (88%) for Ti-mesh group respectively. Conclusions: Within the limitation of the study, it was concluded that mean defect height and width after 6 months were statistically significant within the group without significant difference between them, although defect resolution was better in Ti-mesh.Keywords: collagen membrane, dehiscence, dental implant, horizontal bone, augmentation, ti-mesh
Procedia PDF Downloads 111358 Study of Demographic, Hematological Profile and Risk Stratification in Chronic Myeloid Leukemia Patients
Authors: Rajandeep Kaur, Rajeev Gupta
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Background: Chronic myeloid leukemia (CML) is the most common leukaemia in India. The annual incidence of chronic myeloid leukemia in India was originally reported to be 0.8 to 2.2 per 1,00,000 population. CML is a clonal disorder that is usually easily diagnosed because the leukemic cells of more than 95% of patients have a distinctive cytogenetic abnormality, the Philadelphia chromosome (Ph1). The approval of tyrosine kinase inhibitors (TKIs), which target BCR-ABL1 kinase activity, has significantly reduced the mortality rate associated with chronic myeloid leukemia (CML) and revolutionized treatment. Material and Methods: 80 diagnosed cases of CML were taken. Investigations were done. Bone marrow and molecular studies were also done and with EUTOS, patients were stratified into low and high-risk groups and then treatment with Imatinib was given to all patients and the molecular response was evaluated at 6 months and 12 months follow up with BCR-ABL by RT-PCR quantitative assay. Results: In the study population, out of 80 patients in the study population, 40 were females and 40 were males, with M: F is 1:1. Out of total 80 patients’ maximum patients (54) were in 31-60 years age group. Our study showed a most common symptom of presentation is abdominal discomfort followed by fever. Out of the total 80 patients, 25 (31.3%) patients had high EUTOS scores and 55 (68.8%) patients had low EUTOS scores. On 6 months follow up 36.3% of patients had Complete Molecular Response, 16.3% of patients had Major Molecular Response and 47.5% of patients had No Molecular Response but on 12 months follow up 71.3% of patients had Complete Molecular Response, 16.25% of patients had Major Molecular Response and 12.5% patients had No Molecular Response. Conclusion: In this study, we found a significant correlation between EUTOS score and Molecular response at 6 months and 12 months follow up after Imatinib therapy.Keywords: chronic myeloid leukemia, European treatment and outcome study score, hematological response, molecular response, tyrosine kinase inhibitor
Procedia PDF Downloads 101357 Student Debt Loans and Labor Market Outcomes: A Lesson in Unintended Consequences
Authors: Sun-Ki Choi
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The U.S. student loan policy was initiated to improve the equality of educational opportunity and help low-income families to provide higher education opportunities for their children. However, with the increase in the average student loan amount, college graduates with student loans experience problems and restrictions in their early-career choices. This study examines the early career labor market choices of college graduates who obtained student loans to finance their higher education. In this study, National Survey of College Graduates (NSCG) data for 2017 and 2019 was used to estimate the effects of student loans on the employment status and current job wages of graduates with student loans. In the analysis, two groups of workers, those with student loans and those without loans, were compared. Using basic models and Mahalanobis distance matching, it was found that graduates who rely on student loans to finance their education are more likely to participate in the labor market than those who do not. Moreover, in entry-level jobs, graduates with student loans receive lower salaries than those without student loans. College graduates make job-related decisions based on their current and future wages and fringe benefits. Graduates with student loans tend to demonstrate risk-averse behaviors due to their financial restrictions. Thus, student loan debt creates inequity in the early-career labor market for college graduates. Furthermore, this study has implications for policymakers and researchers in terms of the student loan policy.Keywords: student loan, wage differential, unintended consequences, mahalanobis distance matching
Procedia PDF Downloads 118356 Improving Sample Analysis and Interpretation Using QIAGENs Latest Investigator STR Multiplex PCR Assays with a Novel Quality Sensor
Authors: Daniel Mueller, Melanie Breitbach, Stefan Cornelius, Sarah Pakulla-Dickel, Margaretha Koenig, Anke Prochnow, Mario Scherer
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The European STR standard set (ESS) of loci as well as the new expanded CODIS core loci set as recommended by the CODIS Core Loci Working Group, has led to a higher standardization and harmonization in STR analysis across borders. Various multiplex PCRs assays have since been developed for the analysis of these 17 ESS or 23 CODIS expansion STR markers that all meet high technical demands. However, forensic analysts are often faced with difficult STR results and the questions thereupon. What is the reason that no peaks are visible in the electropherogram? Did the PCR fail? Was the DNA concentration too low? QIAGEN’s newest Investigator STR kits contain a novel Quality Sensor (QS) that acts as internal performance control and gives useful information for evaluating the amplification efficiency of the PCR. QS indicates if the reaction has worked in general and furthermore allows discriminating between the presence of inhibitors or DNA degradation as a cause for the typical ski slope effect observed in STR profiles of such challenging samples. This information can be used to choose the most appropriate rework strategy.Based on the latest PCR chemistry called FRM 2.0, QIAGEN now provides the next technological generation for STR analysis, the Investigator ESSplex SE QS and Investigator 24plex QS Kits. The new PCR chemistry ensures robust and fast PCR amplification with improved inhibitor resistance and easy handling for a manual or automated setup. The short cycling time of 60 min reduces the duration of the total PCR analysis to make a whole workflow analysis in one day more likely. To facilitate the interpretation of STR results a smart primer design was applied for best possible marker distribution, highest concordance rates and a robust gender typing.Keywords: PCR, QIAGEN, quality sensor, STR
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