Biomarker Assay Development: Urinary Titin in Becker Muscular Dystrophy

Mutations in a structural muscle protein called dystrophin result in muscle fiber degradation and diseases such as Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD). Such muscle fiber degradation can result in large titin fragments being released into serum and excreted into the urine. Compared to current methods using muscle biopsy and serum collection, our study utilizes urine as a potential non-invasive method for monitoring disease progression in BMD by quantifying urinary titin fragments. This is done through development of an immunoassay based on the enzyme linked immunosorbent assay (ELISA) format using liposomal technology as a method of detection. The development of this platform is expected to provide discrimination between disease severities in BMD patients in hopes to better monitor disease progression and could be used for other muscular dystrophies and cardiomyopathies impacted by titin. Such as titin-related mutations that cause diseases like Emery-Dreifuss, limb-girdle, and tibial muscular dystrophy.https://orb.binghamton.edu/research_days_posters_2023/1049/thumbnail.jp

Development of Assay Platforms for Monitoring Human C-Reactive Protein

It is imperative to have rapid diagnostic assays available that provide healthcare workers with a rapid yes/no or semi-quantitative response to a biomarker of interest. Agglutination assays use the clustering of antibodies in the presence of an antigen to semi-quantitatively monitor specific protein levels. Our research details the development of a latex agglutination test (LAT) for the detection of C-reactive protein (CRP), an important marker of inflammation in various disease states, at physiologically-relevant levels. Blue latex beads were covalently coated with Protein A for oriented antibody immobilization, then functionalized with anti-CRP antibody at various concentrations. We determined the optimal concentrations of Protein A and anti-CRP and will carry out an assessment of particle size effects on visualization and detectable CRP levels. Further experiments will improve this test’s sensitivity and develop this into a platform assay for other biomarkers. For quantitative measurements in a laboratory environment, we also have developed a sandwich ELISA assay for CRP using anti-CRP conjugated with alkaline phosphatase. These platforms will establish and optimize the immunoassays, then we’ll use novel nanoparticles such as fluorescent liposomes and europium chelate particles to provide greater sensitivity and ease of use versus traditional latex beads or enzymes used for signal amplification.https://orb.binghamton.edu/research_days_posters_spring2020/1020/thumbnail.jp

A Grounded theory of Chinese students\u27 leisure behavior in American university

The number of international students at colleges and universities in the United States increased to a record high of 623,805 in the 2007/08 academic year (Institute of International Education, 2008). Among them, 81,127 (13%) students were from China, which is the second- leading place of origin for students coming to the United States, trailing only India (Institute of International Education, 2008). Due to the importance of international students to culturally diverse make-up of colleges and universities, American institutions have developed support services to assist international students with a variety of special needs ranging from adjusting to the academic requirements, to dealing with cultural factors of being submerged in new societal settings (Heggins & Jackson, 2003). The literature suggests there is one more element that is important in college students’ experience: leisure. Leisure forms a major component of active campus life, spanning a range of activities from daydreaming or drinking beer at the campus pub to tutoring disadvantaged children (Bloland, 1987). However, how international college students spend their leisure time and how their different cultures have impact on their leisure behavior has not been studiedextensively. Few empirical investigations focused on international students and no theory or process model of leisure behavior of international students exists. Therefore, this study intended to develop a theoretic model of Chinese students’ leisure behavior in American universities. In the study, we selected the grounded theory approach to construct a preliminary paradigm model of Chinese student’s leisure behavior based on in-depth interviews

Інформаційне забезпечення контролінгу транспортних процесів агропідприємства

Робота публікується згідно наказу ректора від 21.01.2020 р. №008/од "Про перевірку кваліфікаційних робіт на академічний плагіат 2019-2020 р.р. навчальному році" . Керівник проекту: доцент, к.е.н., Савченко Л.В.Moving agricultural products between different points in the country implies handling issues regarding perishability of products, long and tortuous supply chains marked by the presence of several operators and no alternate roads, the need to maintain a cold chain to guarantee the quality of the final product, consumption behavior and habits, and the role that health aspects and organoleptic quality play in purchasing decisions of consumers, among others. According to Pietro and Timpanaro [45], the cost the agricultural logistics vanes between 20-30% of the cost of the product. This can be even higher depending on the type of chain involved, e.g the distance from origin and the type of transportation considered. Thus, it is important to view the transportation and logistics system as a whole since “the production, exchange, distribution and consumption of agricultural products constitute the organic chain of agriculture reproduction. Any deficiency of them will affect the development of agriculture”. Moreover, it is important the study of distribution networks in order to address the different issues existing between the diverse parties involved in the transportation and distribution systems of products. Daganzo, for example, establishes the principle of distribution network application with the goal of uniting one origin with one destination, one origin to many destinations and many to many systems using transshipment centers and providing methods to solve it. On the other hand, Agra demonstrated that the costs associated with the transport of goods represent a large part of the final cost.Переміщення сільськогосподарської продукції між різними пунктами в країні передбачає вирішення питань щодо швидкопсувних продуктів, довгих та звивистих ланцюгів поставок, що відзначаються наявністю декількох операторів та відсутністю альтернативних доріг, необхідність підтримувати холодний ланцюг, щоб гарантувати якість кінцевої продукції споживча поведінка та звички, а також роль, яку аспекти здоров'я та органолептична якість відіграють, серед іншого, у прийнятті рішень щодо закупівлі. За даними П'єтро та Тімпанаро, вартість сільськогосподарської логістики коливається в межах 20-30% від вартості продукту. Це може бути навіть вище залежно від типу ланцюга, наприклад, відстані від місця походження та виду транспорту, що розглядається. Таким чином, важливо розглядати транспортно-логістичну систему в цілому, оскільки «виробництво, обмін, розподіл та споживання сільськогосподарської продукції становлять органічний ланцюг відтворення сільського господарства. Будь-який їх недолік вплине на розвиток сільського господарства». Більше того, важливим є вивчення розподільчих мереж для вирішення різних питань, що існують між різними сторонами, що беруть участь у системах транспортування та розподілу продукції. Наприклад, Daganzo встановлює принцип застосування мережі розподілу з метою об'єднання одного джерела з одним пунктом призначення, одного джерела для багатьох пунктів призначення та багатьох систем за допомогою перевалочних центрів та надання методів його вирішення. З іншого боку, Agra продемонстрував, що витрати, пов'язані з перевезенням вантажів, становлять значну частину кінцевих витрат

Similarity-based virtual screening using 2D fingerprints

This paper summarises recent work at the University of Sheffield on virtual screening methods that use 2D fingerprint measures of structural similarity. A detailed comparison of a large number of similarity coefficients demonstrates that the well-known Tanimoto coefficient remains the method of choice for the computation of fingerprint-based similarity, despite possessing some inherent biases related to the sizes of the molecules that are being sought. Group fusion involves combining the results of similarity searches based on multiple reference structures and a single similarity measure. We demonstrate the effectiveness of this approach to screening, and also describe an approximate form of group fusion, turbo similarity searching, that can be used when just a single reference structure is available

Emergency Management for Disasters in Malaysian Hotel Industry

This paper aims to identify major emergencies that have the potential to place Malaysian hotels in emergency and disaster situations; investigate how hotels were prepared for emergencies, how they manage and overcome emergencies when occurred; and limitations and factors influencing successful emergency planning and adoption emergency management in Malaysian hotels. Face-to-face interview with managers from three, four and five star hotels from different backgrounds: local; regional; and International in Kuala Lumpur, Subang, and Putrajaya are undertaken. The result revealed that Malaysian hotels are exposed to a wide range of natural and man-made disasters. Malaysian hotels lack proactive emergency planning and a lot of constraints which impede successful emergency planning for disasters in the hotel industry in Malaysia, with emphasizing on the relevant authority’s role to demonstrate emergency management to hotels convincing them to adopt such practices, so they can be able to cope with emergencies effectively

Evaluation of machine-learning methods for ligand-based virtual screening

Machine-learning methods can be used for virtual screening by analysing the structural characteristics of molecules of known (in)activity, and we here discuss the use of kernel discrimination and naive Bayesian classifier (NBC) methods for this purpose. We report a kernel method that allows the processing of molecules represented by binary, integer and real-valued descriptors, and show that it is little different in screening performance from a previously described kernel that had been developed specifically for the analysis of binary fingerprint representations of molecular structure. We then evaluate the performance of an NBC when the training-set contains only a very few active molecules. In such cases, a simpler approach based on group fusion would appear to provide superior screening performance, especially when structurally heterogeneous datasets are to be processed

Physiochemical property space distribution among human metabolites, drugs and toxins

<p>Abstract</p> <p>Background</p> <p>The current approach to screen for drug-like molecules is to sieve for molecules with biochemical properties suitable for desirable pharmacokinetics and reduced toxicity, using predominantly biophysical properties of chemical compounds, based on empirical rules such as Lipinski's "rule of five" (Ro5). For over a decade, Ro5 has been applied to combinatorial compounds, drugs and ligands, in the search for suitable lead compounds. Unfortunately, till date, a clear distinction between drugs and non-drugs has not been achieved. The current trend is to seek out drugs which show metabolite-likeness. In identifying similar physicochemical characteristics, compounds have usually been clustered based on some characteristic, to reduce the search space presented by large molecular datasets. This paper examines the similarity of current drug molecules with human metabolites and toxins, using a range of computed molecular descriptors as well as the effect of comparison to clustered data compared to searches against complete datasets.</p> <p>Results</p> <p>We have carried out statistical and substructure functional group analyses of three datasets, namely human metabolites, drugs and toxin molecules. The distributions of various molecular descriptors were investigated. Our analyses show that, although the three groups are distinct, present-day drugs are closer to toxin molecules than to metabolites. Furthermore, these distributions are quite similar for both clustered data as well as complete or unclustered datasets.</p> <p>Conclusion</p> <p>The property space occupied by metabolites is dissimilar to that of drugs or toxin molecules, with current drugs showing greater similarity to toxins than to metabolites. Additionally, empirical rules like Ro5 can be refined to identify drugs or drug-like molecules that are clearly distinct from toxic compounds and more metabolite-like. The inclusion of human metabolites in this study provides a deeper insight into metabolite/drug/toxin-like properties and will also prove to be valuable in the prediction or optimization of small molecules as ligands for therapeutic applications.</p

Novel curcumin- and emodin-related compounds identified by in silico 2D/3D conformer screening induce apoptosis in tumor cells

BACKGROUND: Inhibition of the COP9 signalosome (CSN) associated kinases CK2 and PKD by curcumin causes stabilization of the tumor suppressor p53. It has been shown that curcumin induces tumor cell death and apoptosis. Curcumin and emodin block the CSN-directed c-Jun signaling pathway, which results in diminished c-Jun steady state levels in HeLa cells. The aim of this work was to search for new CSN kinase inhibitors analogue to curcumin and emodin by means of an in silico screening method. METHODS: Here we present a novel method to identify efficient inhibitors of CSN-associated kinases. Using curcumin and emodin as lead structures an in silico screening with our in-house database containing more than 10(6 )structures was carried out. Thirty-five compounds were identified and further evaluated by the Lipinski's rule-of-five. Two groups of compounds can be clearly discriminated according to their structures: the curcumin-group and the emodin-group. The compounds were evaluated in in vitro kinase assays and in cell culture experiments. RESULTS: The data revealed 3 compounds of the curcumin-group (e.g. piceatannol) and 4 of the emodin-group (e.g. anthrachinone) as potent inhibitors of CSN-associated kinases. Identified agents increased p53 levels and induced apoptosis in tumor cells as determined by annexin V-FITC binding, DNA fragmentation and caspase activity assays. CONCLUSION: Our data demonstrate that the new in silico screening method is highly efficient for identifying potential anti-tumor drugs