A statistical method for revealing form-function relations in biological networks

Over the past decade, a number of researchers in systems biology have sought to relate the function of biological systems to their network-level descriptions -- lists of the most important players and the pairwise interactions between them. Both for large networks (in which statistical analysis is often framed in terms of the abundance of repeated small subgraphs) and for small networks which can be analyzed in greater detail (or even synthesized in vivo and subjected to experiment), revealing the relationship between the topology of small subgraphs and their biological function has been a central goal. We here seek to pose this revelation as a statistical task, illustrated using a particular setup which has been constructed experimentally and for which parameterized models of transcriptional regulation have been studied extensively. The question "how does function follow form" is here mathematized by identifying which topological attributes correlate with the diverse possible information-processing tasks which a transcriptional regulatory network can realize. The resulting method reveals one form-function relationship which had earlier been predicted based on analytic results, and reveals a second for which we can provide an analytic interpretation. Resulting source code is distributed via http://formfunction.sourceforge.net.Comment: To appear in Proc. Natl. Acad. Sci. USA. 17 pages, 9 figures, 2 table

Molecular Mechanisms of Transcription through Single-Molecule Experiments

Transcription represents the first step in gene expression. It is therefore not surprising that transcription is a highly regulated process and its control is essential to understand the flow and processing of information required by the cell to maintain its homeostasis. During transcription, a DNA molecule is copied into RNA molecules that are then used to translate the genetic information into proteins; this logical pattern has been conserved throughout all three kingdoms of life, from Archaea to Eukarya, making it an essential and fundamental cellular process. Even though some viruses that encode their genome in an RNA molecule use it as a template to make mRNA, others synthesize an intermediate DNA molecule from the RNA, a process known as reverse transcription, from which regular transcription of viral genes can then proceed in the host cells

Non-cash payment method using QR codes in an automated microcontroller-based vending machine

This thesis report is submitted in partial fulfillment of the requirements for the degree of Bachelor of Science in Electrical and Electronic Engineering, 2014.Cataloged from PDF version of thesis report.Includes bibliographical references (page 42).The purpose of this thesis project is to implement a micro-controller-based automated vending machine which uses codes as a method for authorization of payments of online accounts to implement a non cash payment method for a contact less mobile payment system. Once a user places his/her order in the vending machine a QR (quick response) code is generated which holds all of the information of the user's order. An application is used to scan that QR code. The QR code once scanned with that application, populates the information of the order and sends that information to a web server only after the user’s approval for using their online account for payment. This web server takes this input from the user and processes the payment. The transaction is made from the web server with an online payment platform which holds the user's account. After the transaction is made, a second QR code, which stores the user's order information and authorization, is sent to the user's application from the server. User displays the QR code and it is scanned by the vending machine's scanner to release the desired product(s) thus making the process contact less.Md. Shahidur RahmanShamiha Yeasin BintuSidratul AmanB. Electrical and Electronic Engineerin

Nonlinear Protein Degradation and the Function of Genetic Circuits

The functions of most genetic circuits require sufficient degrees of cooperativity in the circuit components. While mechanisms of cooperativity have been studied most extensively in the context of transcriptional initiation control, cooperativity from other processes involved in the operation of the circuits can also play important roles. In this study, we examine a simple kinetic source of cooperativity stemming from the nonlinear degradation of multimeric proteins. Ample experimental evidence suggests that protein subunits can degrade less rapidly when associated in multimeric complexes, an effect we refer to as cooperative stability. For dimeric transcription factors, this effect leads to a concentration-dependence in the degradation rate because monomers, which are predominant at low concentrations, will be more rapidly degraded. Thus cooperative stability can effectively widen the accessible range of protein levels in vivo. Through theoretical analysis of two exemplary genetic circuits in bacteria, we show that such an increased range is important for the robust operation of genetic circuits as well as their evolvability. Our calculations demonstrate that a few-fold difference between the degradation rate of monomers and dimers can already enhance the function of these circuits substantially. These results suggest that cooperative stability needs to be considered explicitly and characterized quantitatively in any systematic experimental or theoretical study of gene circuits.Comment: 42 pages, 10 figure

Stochastic approach to molecular interactions and computational theory of metabolic and genetic regulations

Binding and unbinding of ligands to specific sites of a macromolecule are one of the most elementary molecular interactions inside the cell that embody the computational processes of biological regulations. The interaction between transcription factors and the operators of genes and that between ligands and binding sites of allosteric enzymes are typical examples of such molecular interactions. In order to obtain the general mathematical framework of biological regulations, we formulate these interactions as finite Markov processes and establish a computational theory of regulatory activities of macromolecules based mainly on graphical analysis of their state transition diagrams. The contribution is summarized as follows: (1) Stochastic interpretation of Michaelis-Menten equation is given. (2) Notion of \textit{probability flow} is introduced in relation to detailed balance. (3) A stochastic analogy of \textit{Wegscheider condition} is given in relation to loops in the state transition diagram. (4) A simple graphical method of computing the regulatory activity in terms of ligands' concentrations is obtained for Wegscheider cases.Comment: 20 pages, 13 figure

Dynamics of epigenetic regulation at the single-cell level

Chromatin regulators play a major role in establishing and maintaining gene expression states. Yet how they control gene expression in single cells, quantitatively and over time, remains unclear. We used time-lapse microscopy to analyze the dynamic effects of four silencers associated with diverse modifications: DNA methylation, histone deacetylation, and histone methylation. For all regulators, silencing and reactivation occurred in all-or-none events, enabling the regulators to modulate the fraction of cells silenced rather than the amount of gene expression. These dynamics could be described by a three-state model involving stochastic transitions between active, reversibly silent, and irreversibly silent states. Through their individual transition rates, these regulators operate over different time scales and generate distinct types of epigenetic memory. Our results provide a framework for understanding and engineering mammalian chromatin regulation and epigenetic memory

Import of Information Sources in the Industrial Purchase Decision in Maiduguri, Borno State Nigeria

The basic objective of any industrial activity is to develop, manufacture and market products that can meet identified customer/consumer needs and wants at a profit. In order to accomplish this objective "men machines and management" must be carefully acquired and coordinated. A field survey was employed through semi-structured in-depth interviews to secure the basic data on the general purchasing procedure. Some specific purchase case studies were employed to examine the functions of information in the adoption and use of a product. Both qualitative and quantitative analyses were utilised for the discussion of results. The study focuses on the information sources of industrial buyers in the purchase of three different categories of items from ten different organisations purposively selected in Maiduguri, Nigeria. The findings indicate that the problem of shortages and disrupted supply of raw materials equipment among Nigerian industries can be attributed to lack of active search and qualification of sources of supplies in the purchasing procedure. The buyers’ search efforts are inadequate and they rely much on suppliers’ salesmen for almost all their information. The suppliers’ personal calls are considered the most important source of information of organisational buyers. The sort of information required by these buyers mostly cantered on price, quality and reputation of supplier, non-task factors largely influence buyers’ decisions as they lack more formalised procedure for search and analysis. It was recommended that information for buying industrial products are needed at all stages of the decision processes and therefore information should be directed at the right people, right time, through personal selling effort than those selling consumer items. The industrial salesmen must contact potential buyers earlier and must play greater role in generating interest and re-enforce contacts and approaches at the final stage of evaluation and trial of the adoption process. Keywords: Information Sources, Adoption Process, Industrial Purchasing, Decision Makin

Mitigation of off-target toxicity in CRISPR-Cas9 screens for essential non-coding elements.

Pooled CRISPR-Cas9 screens are a powerful method for functionally characterizing regulatory elements in the non-coding genome, but off-target effects in these experiments have not been systematically evaluated. Here, we investigate Cas9, dCas9, and CRISPRi/a off-target activity in screens for essential regulatory elements. The sgRNAs with the largest effects in genome-scale screens for essential CTCF loop anchors in K562 cells were not single guide RNAs (sgRNAs) that disrupted gene expression near the on-target CTCF anchor. Rather, these sgRNAs had high off-target activity that, while only weakly correlated with absolute off-target site number, could be predicted by the recently developed GuideScan specificity score. Screens conducted in parallel with CRISPRi/a, which do not induce double-stranded DNA breaks, revealed that a distinct set of off-targets also cause strong confounding fitness effects with these epigenome-editing tools. Promisingly, filtering of CRISPRi libraries using GuideScan specificity scores removed these confounded sgRNAs and enabled identification of essential regulatory elements

Effects of Marketing Mix Strategy on Performance of Small Scale Businesses in Maiduguri Metropolitan, Borno State Nigeria

The study was designed to examine the effect of Marketing Strategy on Performance of Small Scale Business in Maiduguri, Borno State, Nigeria. The objectives of the study are to explore how Marketing mix elements are managed and they impacted on the performance of small scale enterprises in Maiduguri. Method of data collection consists of primary and secondary sources. Method of data analysis utilized was multiple regression. The study found that marketing strategy (product, price, promotion and place,) were significantly independent and joint predictors of business performance. Each one has its unique contribution and impact to the performance of the small Businesses. This also shows the importance of the marketing strategy no matter how small the Business may be. Its performance is proportionately depends and goes with the marketing strategy applied. The study therefore recommends that since small Businesses have high potential and opportunity for growth, instituting appropriate and adequate measures of marketing strategy in their Business practice will go a long way in Business success. Keywords: Marketing Mix, Marketing Strategy, Small Scale Enterprises, Performanc

A COMPARISON OF KAPLAN-MEIER AND CUMULATIVE INCIDENCE ESTIMATE IN THE PRESENCE OR ABSENCE OF COMPETING RISKS IN BREAST CANCER DATA

Statistical techniques such as Kaplan-Meier estimate is commonly used and interpreted as the probability of failure in time-to-event data. When used on biomedical survival data, patients who fail from unrelated or other causes (competing events) are often treated as censored observations. This paper reviews and compares two methods of estimating cumulative probability of cause-specific events in the present of other competing events: 1 minus Kaplan-Meier and cumulative incidence estimators. A subset of a breast cancer data with three competing events: recurrence, second primary cancers, and death, was used to illustrate the different estimates given by 1 minus Kaplan-Meier and cumulative incidence function. Recurrence of breast cancer was the event of interest and second primary cancers and deaths were competing risks.The results indicate that the cumulative incidences gives an appropriate estimates and 1 minus Kaplan-Meier overestimates the cumulative probability of cause-specific failure in the presence of competing events. In absence of competing events, the 1 minus Kaplan-Meier approach yields identical estimates as the cumulative incidence function.The public health relevance of this paper is to help researchers understand that competing events affect the cumulative probability of cause-specific events. Researchers should use methods such as the cumulative incidence function to correctly estimate and compare the cause-specific cumulative probabilities