Genetic Profiling in Soft Tissue Sarcoma

Soft tissue sarcomas (STS) are a heterogeneous group of highly malignant mesenchymal tumors that account for ~1% of all malignancies. Frequent heterogeneity and pleomorphism along with suboptimal diagnostic reproducibility and insufficient prognostic markers make clinical management of these tumors difficult. This thesis has applied microarray-based gene expression and copy-number profiling to STS. The studies provide clues to the genetic pathways involved in STS development and identify profiles linked to diagnosis and prognosis. The results from Study I that concerns intratumor versus intertumor heterogeneity of gene expression profiles in malignant fibrous histiocytoma (MFH) and leiomyosarcoma (LMS), suggest that intratumor heterogeneity may be particularly relevant in small tumor series and thus serve as a reminder to run larger sample sets for increased reliability. Study II established expression patterns related to the SS18-SSX fusion variants and metastatic potential in synovial sarcoma (SS). The differential expression of various developmental genes, transcription factors, histones, and metallothioneins suggests that the gene fusion variants have distinct downstream effects. In Study III, 177 STS of mixed histopathological subtypes were profiled using cDNA microarrays. Distinct gene expression patterns were identified in subtypes with specific translocations or mutations. Herein, frequent upregulation of developmental genes, from e.g. the Wingless and Hedgehog signaling pathways, was demonstrated. The more pleomorphic STS showed overexpression of genes involved in proliferation, adhesion, motility and protein degradation. Moreover, a prognostic signature partly characterized by hypoxia-related genes was identified within the pleomorphic STS. Study IV applied array-based comparative genomic hybridization in MFH and LMS, and demonstrated extensive genetic complexity with multiple recurrent gains and losses, novel amplifications and homozygous deletions. Losses in chromosomal regions 6q14 and 7q36 provided prognostic information independent of previously established risk factors. In summary, these studies demonstrate the potential of genetic profiling in STS and herein, define intratumor heterogeneity, demonstrate that gene fusion variants in SS yield different downstream effects, identify diagnostic and prognostic subsets within STS, and in the pleomorphic tumors, discern prognostically important alterations within the plethora of genetic aberrations that characterize many STS

Antioxidant Combination of High Phosphatidylserine (PS) Lecithin with Mixed Tocopherol in Soybean Oil-in-Water Emulsion: Effect of pH and Salt

Lipid oxidation is one of the major challenges faced by the food industry as it contributes to the loss of nutritional quality and loss of flavor in food products. Studies have shown that naturally occurring phospholipids like phosphatidylserine (PS) and phosphatidylethanolamine (PE) can regenerate oxidized tocopherols and help delay the lipid oxidation in bulk oils and oil-in-water emulsions. Since consumers desire simpler and cleaner labels, without chemically synthesized antioxidants, this research is of great interest. The combination of PS and PE with tocopherols has already been studied. However, PS was a better antioxidant in combination with tocopherols in the oil-in-water emulsion system whereas PE was a better antioxidant in combination with tocopherols in bulk oils. But obtaining pure phospholipids is an expensive deal, therefore, this study uses the more economical alternative, high phosphatidylserine (PS) lecithin in combination with mixed tocopherols in soybean oil-in-water system. PS (30 µmol/kg emulsion) along with mixed tocopherols (3 µmol/kg emulsion) were dissolved in oil and emulsions stabilized by Tween20 were prepared. To determine the most effective concentration of mixed tocopherols, 0.5, 1.0, and 3 µmole of tocopherols/kg emulsion were used at pH of 3 and 7. Tocopherol with a concentration of 3 µmole/kg emulsion was found to be the most effective at pH 3. Tocopherols showed an extended lag phase at lower pH. The synergistic activities of authentic PS and high PS lecithin were compared in combination with tocopherol under similar conditions. They both had an almost similar lag phase. This combination was then tested for different pH of 3 and 7 and different salt concentrations of (0.5, 1, and 1.5 wt% of the emulsion) at pH 7 to determine the effects of external factors on the synergistic antioxidant combination. It was observed that the combination had extended antioxidant ability at lower pH of 3 whereas salt had no effect on the combination. The results showed that high PS lecithin forms a synergistic combination with mixed tocopherols to increase the lag phase in oil-in-water emulsions and can be used as a clean label antioxidant for oil-in-water emulsions

Algorithms for Covering Barrier Points by Mobile Sensors with Line Constraint

In this thesis, we develop efficient algorithms for the problem of covering barrier points by mobile sensors. Each sensor is represented by a point in the plane with the same covering range r so that any point within distance r from the sensor can be covered by the sensor. Given a set B of m points (called “barrier points”) and a set S of n points (representing the “sensors”) in the plane, the problem is to move the sensors so that each barrier point is covered by at least one sensor and the maximum movement of all sensors is minimized. The problem is NP-hard. In this thesis, we consider two line-constrained variations of the problem and present efficient algorithms that improve the previous work. In the first problem, all sensors are given on a line l and are required to move on l only while the barrier points can be anywhere in the plane. We propose an O((n+m) log(n+m)) time algorithm for the problem. We also consider the weighted case where each sensor has a weight; we give an O((m+n) log2(m+n)) time algorithm for this case. In the second problem, all barrier points are on l while all sensors are in the plane but are required to move to l to cover all barrier points. We solve the weighted case in O(mlogm+nlog2n) time

Improving HPV Vaccination Initiation and Completion Rates: A QI Project

Human papillomavirus (HPV) is a common sexually transmitted infection in the United States and is the cause of most cervical cancers in women, as well as anogenital cancers, oropharyngeal cancer, and genital warts in both men and women (Centers for Disease Control [CDC], 2014b). The HPV vaccine is recommended for preteen girls and boys to protect against HPV infections (CDC, 2011). In line with the goal of Healthy People 2020, the purpose of this evidence-based quality improvement (QI) project was to implement a text message reminder system, and calculate the completion rate of the 3-dose HPV vaccination series among adolescents in a pediatric clinic in a small city in Texas. The results were compared to the vaccination rates from a previously used reminder system. The project was of a single-group. pre-test–post-test design. Participants were adolescents aged 9–18 years who had begun, or were set to begin, the 3-dose HPV vaccine series during the project implementation period (October 2015–April 2016). Data from a random review of 100 charts of adolescents reminded using the prior system (prior to implementation) for the same vaccine appointments were used for comparison with the new reminder system data. Enrollees received up to 3 text message reminders for each appointment. They were surveyed to evaluate their preference of a reminder system. Using data from the prior system (n = 100), 11% of adolescents completed the three-dose HPV vaccine series compared to 46.9% from the text messaging system group (n = 49). Both groups showed a better completion rate among females. Based on surveys, 24 (80%) were in favor of text message reminders. This project shows that text message reminders offer an effective method of sending appointment reminders to increase the initiation and completion rates of the HPV vaccine series

A study to analyse the effect of various positions along with coughing and huffing techniques on respiratory parameters in smokers

INTRODUCTION: Smoking is the inhalation of the smoke of the burning tobacco. If smoking is directly related to a decrease in pulmonary function, then people who smoke more than one pack a week or heavy smokers will show a dramatic difference in pulmonary measurements such as vital capacity, forced expired volume, Forced Vital Capacity and the ratio of Forced Expired Volume in one second to Forced Vital Capacity compared to mild smokers or nonsmokers. Nicotine the active ingredient in tobacco, is inhaled into the lungs, where most of it stays. The rest passes into the blood stream, reaching the brain in about 10seconds and dispersing throughout the body in about a20 seconds. OBJECTIVES: 1. To find out the effect of sitting position along with the interventions of coughing and huffing on FEV1, FEV1/FVC and FEV1/FEV6 in smokers. 2. To find out the effect of supine position along with the interventions of coughing and huffing on FEV1, FEV1/FVC and FEV1/FEV6 in smokers. 3. To find out the effect of 45° prone position along with the interventions of coughing and huffing on FEV1, FEV1/FVC and FEV1/FEV6 in smokers. METHODOLOGY: Study Design: One group pretest and post test experimental study design. Study Setting: Study was conducted at physiotherapy outpatient department, K.G. College of Physiotherapy, Saravanampatti, Coimbatore-35. Study Duration: Study was conducted for a period of 6 month. Study Subjects: Based on selection criteria, 20 subjects were selected for the study. CRITERIA FOR SELECTION: INCLUSION CRITERIA: Age group between 30 and 40 years, Male subjects, Smokers, Subjects with BMI from 20-29.9 kg/m, Subjects who are willing to participate. EXCLUSION CRITERIA: Subjects with cardio vascular disease, Subjects with neuro muscular disease, Subjects with acute respiratory disease within the previous 6 weeks, Uncooperative subjects, Subjects unwilling to participate. RESULTS: The results of this study are similar to the findings of Atsuhiro [et. al.], 2009. The reason for increased FEV1, FEV1/FVC and FEV1/FEV6 in 45°rotative prone and sitting position might be due to rectus abdominus muscle and its force production ability with respect to hip joint status. During forced expiration the rectus abdominus muscle is mainly working. In the sitting and 45°rotative prone position, both the hip joints are in flexion. It gives an advantage for excessive force production to rectus muscle by increasing its efficiency. But, in case of supine position both the hip joints are in extension where the rectus muscle cannot work efficiently and thereby the forced expiration cannot be achieved adequately. Moreover, the effectiveness of coughing and huffing techniques has been proved by many researchers like Pryor et al, 1999. This\ud study has also got the similar improvement on respiratory parameters following four weeks of coughing and huffing interventions in smokers. CONCLUSION: This study concludes that there is a significant improvement on FEV1, FEV1/FVC and FEV1/FEV6 following the interventions of coughing and huffing techniques in smokers. While considering three different positions, 45° rotative prone position is the most effective position for the transfer of the intrabronchial secretions to the proximal airway. Thus this study also concludes that 45° rotative prone position is effective for coughing up secretions especially in smoker population

A COMPREHENSIVE REVIEW ON ADULTERATION AND SUBSTITUTION OF CRUDE DRUGS

Herbs are an effective source of Ayurvedic medicine and other traditional medicines as well as modern medicine. Faced with the challenges of modern medicine, the world is shifting toward Ayurvedic theories of health management. In the treatment of the disease, the use of drugs is not limited. This increases the demand for raw materials exponentially. However, production growth is still linear. Rapid depletion of resources creates major problems. To fill the deficit, advances in adulteration and substitution are becoming more prevalent. This adulteration and substitution are a burning problem in an industry that threatens the integrity of Ayurvedic system of medicine. Imprecise knowledge, misidentification, deforestation, and personal gain have led to adulteration. Therefore, an understanding of all ways of adulteration and substitutions is needed to amend this illegal act and maximize consumer safety. This article focuses on adulteration, its types and various methods of adulteration, as well as the concept of substitution, reasoning, and its types. Attempts have also been made to differentiate these two related terms

Design, Synthesis and Catalytic Activity of Di-N-Heterocyclic Carbene Complexes of Nickel and Palladium

N-heterocyclic carbenes (NHC) have widely been used as spectator ligands in organometallic chemistry. Chelating bidentate di-N-heterocyclic carbenes (diNHC) provide additional entropic stability to their complexes relative to monodentate analogues. The steric and electronic environment around the metal centre can be fine-tuned by varying the substituents on the nitrogen atoms of the diNHC ligand. Synthesis and characterization of air and moisture stable bis(diimidazolylidene)nickel(II) complexes, [(diNHC)2Ni]2+, and their corresponding silver(I) and palladium(II) analogues are described. Investigations into the catalytic potential of diNHC complexes of nickel as an alternative to palladium systems in carbon-carbon coupling reactions are discussed. In the Suzuki-Miyaura coupling reaction, the [(diNHC)2Ni]2+ complex was active for the coupling of aryl chlorides as well as aryl fluorides. The analogously synthesized Pd(II) complexes resulted in formation of (diNHC)PdCl2 species which were not active for the coupling of aryl fluorides. “Transition-metal free” coupling reactions were investigated and the results indicated that in the Mizoroki-Heck reaction, aryl iodides could be activated in the absence of nickel or palladium precatalysts when using Na2CO3 or NEt3 as base, while in the Suzuki-Miyaura reaction, aryl iodides and aryl bromides could be activated without any precatalyst when K3PO4 was used as base. A general route into the synthesis of non-symmetrically substituted ligand precursors has been developed. Synthesis and characterization of non-symmetrically substituted ligand precursors, and their corresponding silver(I), palladium(II) and nickel(II) complexes are described. The activity of one of the non-symmetrically substituted (diNHC)Pd(II) complexes in the Suzuki-Miyaura coupling reaction of bulky substrates has been investigated. Non-symmetrically substituted diNHC ligand precursors with a hemi-labile pyridine arm have been synthesized and their corresponding Ni(II) and Pd(II) complexes are described. Attempts to synthesize three-coordinate Pd(II) complexes using bulky â-diketiminato ligands are also discussed

Lower-Rim Substituted Calixarenes and Their Applications

This review discusses in detail “calixarenes” since their discovery as by-products of the phenol formaldehyde bakelites till the present scenario wherein calixarene has assumed a new dimension in the field of supramolecular chemistry. Extensive literature exists for calixarenes; but herein we have tried to concentrate on the different lower-rim modified calixarenes with their potential applications. An attempt has also been made to critically evaluate the synthesis procedures for different lower-rim substituted calixarenes