Novel Analytical Methods Combining Non-Denaturing Chromatography and Mass Spectrometry to Study Biopolymer Structure and Interactions

Biotherapeutics, an emerging class of medicines containing biopolymers (e.g., proteins, peptide, and polysaccharides) have been developed for a variety of indications including cancer, autoimmune, genetic, and blood diseases. Among these biopolymers protein therapeutics have been the rapidly growing segment in the pharmaceutical industry. This trend combined with the complexity of proteins has necessitated the development of powerful and robust analytical methods to study their structure and interactions with physiological partners. Mass spectrometry (MS) has become an indispensable tool to analyze various attributes of protein drugs such as profiling of intact mass, amino acid sequencing, and post translational modifications (PTMs). In this work novel analytical methods have been developed by combining non-denaturing chromatographic separations (such as size exclusion chromatography and ion exchange chromatography) with native ESI MS. In addition to providing information of mass and non-covalent assemblies, native ESI MS has an advantage of probing conformational integrity of proteins by analyzing ionic charge state distributions in the mass spectrum. Size exclusion chromatography with online native ESI MS detection method developed in this work allowed characterization of higher order structure of proteins and probe aggregation propensity. Using the same SEC/native ESI MS workflow a method to find kinetics and equilibrium binding constant of transient protein interactions have also been developed. Combination of ion exchange chromatography (IXC) with native ESI MS and MS/MS detection was developed and shown to be effective in characterization of positional isomers of protein conjugates and PTMs of a biotherapeutic recombinant human interferon beta 1a. To characterize highly heterogeneous PEGylated glycoprotein (conjugated with a 20kDa PEG) analytical methods using IXC/native ESI MS combined with limited charge reduction and collisional activation were developed

Method of Moment Analysis of Partially Shielded Chiral Bodies of Revolution

A chiral body of revolution (BOR) which is partially covered by a thin conducting shield is analyzed using the method of moments (MOM). The axisymmetric system is excited by a plane wave. The total internal fields and the far scattered fields are computed. The problem is solved using the surface equivalence principle. The scattered fields outside the structure are assumed to be produced by an equivalent magnetic surface current that exists on the unshielded part of the BOR surface and an external equivalent electric surface current that exists over all of the BOR surface . These two currents are assumed to radiate in the unbounded external medium. Similarly, the total internal fields are assumed to be produced by the negative of the above magnetic current and an internal equivalent electric surface current that exists over all of the BOR surface, but is the negative of an independent unknown only on the shielded part of . These two currents radiate in the unbounded internal medium. Enforcing continuity of the tangential components of total electric field (E) and total magnetic field (H) on S gives a two coupled integral equations for the two unknown surface currents. The two unknown surface currents are the external equivalent electric surface current and the union of magnetic current ( ) on the unshielded part of and the negative of the internal equivalent electric surface current on the shielded part of . The method of moments as applied to bodies of revolution is used to solve these integral equations numerically. Piecewise linear variation of the currents is assumed along the generating curve of the BOR. The variation of the currents along the circumferential direction is represented by Fourier series. An approximate Galerkin\u27s method is used for testing. Conical and spherical BORs are studied. Computed results for the partially shielded spherical chiral body are in excellent agreement with other data. Theoretical framework developed in chapters two through six factually validated the underlying firm foundation of mathematical physics and sound computational electromagnetic methods of our theory by producing correct scattered fields and radar cross sections of the chiral and perfectly conducting sphere, chiral and perfectly conducting cylinder, chiral and perfectly conducting cone. Chapter seven demonstrates the soundness of the theoretical foundation of this thesis by producing computed results and graphs of not only the case of a perfectly conducting sphere, cylinder and cone but those of the chiral sphere, chiral cylinder, and chiral cone and those of the chiral sphere, chiral cylinder and chiral cone partially covered by rotationally symmetric perfectly conducting surface. The computed results and graphs obtained in chapter seven by the application of our theoretical framework were almost one hundred percent accurate with respect to the conformability of our graph mappings, form of our graphs and accuracy of our graph readings with respect to analytically calculated results and graphs. Our computed results and graphs with respect to the computed results and graphs of early research works that used numerical approach distinctly different than ours were in good agreement

Icatibant is not an appropriate treatment option for ACE-inhibitor induced angioedema of the head and neck

A critical appraisal and clinical application of Sinert T, Levy P, Bernstein JA, et al. Randomized trial of icatibant for angiotensin-converting enzyme inhibitor-induced upper airway angioedema. J Allergy Clin Immunol Pract. 2017;5(5):1402-9. doi: 10.1016/j.jaip.2017.03.00

Signal Fusion and Semantic Similarity Evaluation for Social Media Based Adverse Drug Event Detection

Recent advancements in pharmacovigilance tasks have shown the usage of social media as a resource to obtain real-time signals for drug surveillance. Researchers demonstrated a good potential for the detection of Adverse Drug Events (ADEs) using social media much earlier than the traditional reporting systems maintained by official regulatory authorities like the United States Food and Drug Administration (FDA). Existing automated drug surveillance systems have used various types of social media channels and search query logs for monitoring ADE signals.;In this thesis, we address two key performance issues related to automated drug surveillance systems. The first is to improve the ADE signal detection by analyzing signals from multiple social media channels, and the second is usage of semantic similarity to evaluate ADE narratives detected by drug surveillance systems. Most current approaches for detecting ADEs from social media rely on a single channel: forums or microblogs or query logs. In this study we propose a new methodology to fuse signals from different social media channels. We use graphical causal models to discover potentially hidden connections between data channels, and then use such associations to generate signals for ADEs. Further, prior work have not emphasized much on the language of healthcare consumers, which is often casual and informal in expressing health issues on social media. There is a high potential to miss the semantic similarity between ADE terms extracted from social media and terms from formal official narratives when the two sets of terms do not share exact text. Thus, we exhibit the usage of semantic similarity to enhance accuracy of detected ADEs, and evaluated similarity measurement algorithms developed over biomedical vocabularies in ADE surveillance domain. We experimented on a dataset of drugs which had FDA black box warnings with a retrospective analysis spanning years 2008 to 2015. The results show a better detection rate and an improved performance in terms of precision, recall and timeliness using our proposed methods

A Procedure for Planning Production and Determination of Inventory

At one time excess inventories were considered advantageous, but today they are regarded as the major cause of business failures. Most often, inventories deal the severest blow to the new entrepreneur because he cannot afford to have capital tied up in inventory during a seasonal slump. One of the factors that has aggravated the problem of inventories has been the trend towards product diversification in the past 25 years. Management of inventories is recognized today as one of the key responsibilities in achieving continuous and economical plant operation. Inventory dollars are no longer regarded as a drain on working capital; they are a factor to be used and administered with skill and intelligence. (see more in text

Students’ Precedence of Attributes Related Online Management Education – A RIDIT Approach

This paper sheds light in understanding the effectiveness of online management education by ranking the priority, perception and preference shown by students while they are considering online management education. The students’ precedence of attributes which are in favor and also against the online management education was considered.The ranking of student’s preference and priority of attributes related to online management education was measured and analyzed by RIDIT approach and was inferred that major advantages of online management education includes convenience in performing group assignments, assessments and group projects. Respondents also felt that the quality of courses and pedagogy in online management courses is superior and the Collaborative and interactive learning and teaching were also considered a benefit of performing online management education.  However the major limitations related to online management education were found to be No proper accreditation and certification, No recognition by university or education board and also the credibility of exams, assessments and evaluation system was also skeptical. This paper helps in understanding the areas in which the online management education can enhance its favorable features and thereby overcoming its restrictions and increasing the quality of course delivery by using an innovative digital platform. Keywords: Accreditation, Certification, Collaborative learning, Digital platform, Group Assignments, Online Management education, Pedagogy, RIDIT Analysis

Online practice course development with action research: a case example

Journal ArticleAbstract. Despite the proliferation of online courses in social work, questions still exist about learning practice skills in an online instructional environment. This paper describes a case example of an action-oriented approach to the development of an online practice course. Lessons learned from students' and instructor's perspectives are shared as well as recommendations for future research relative to course development and evaluation of online courses. The study examined student feedback with respect to their overall learning experience. Findings indicated that involving students in the design and development of an online practice course benefited both students and faculty and can be an effective teaching and learning strategy regardless of the instructional medium used

Lateral Sinus Thrombosis in Otology: a Review

Lateral sinus thrombosis (LST) is usually occurs as a complication of middle ear infection. The involvement of lateral sinus during the course of ear infection was a well known complication in preantibiotic days. The decrease in the incidence of LST is due to the introduction of broad-spectrum antibiotics, early diagnosis and surgical treatment. Now, it is a rare complication of otitis media and poses a serious threat that warrants immediate medical and surgical treatment. The classical clinical picture is often changed by previous antibiotic therapy. An awareness of this rare potentially devastating condition and its varied presentations is necessary for early diagnosis and treatment. LST can also occur after head injury

Fungal Infections of the Ear in Immunocompromised Host: a Review

Otomycosis is a fungal infection of the external ear; middle ear and open mastoid cavity.1 Meyer first described the fungal infection of the external ear canal in 1884. External ear canal has an ideal warm humid environment for the proliferation of fungus.2 Although this disease is rarely life threatening, it can presents a challenging and frustrating situation for the otologist and patients due to long term treatment and high rate of recurrence.3 Otomycosis is seen more frequently in immunocompromised patients as compared to immunocompetent persons. Recurrence rate is high in immunocompromised patients and they need longer duration treatment and complications are more frequent in immunocompromised patients