Compensatory evolution within proteins: An experimental assessment

Amino acids within a protein sequence interact to maintain their structure and function. Consequently, mutations at a given functionally significant position can be potentially compensated by a mutation at an interacting position. For instance, a substitution from an amino acid with a small side chain to an amino-acid with a big side chain can be compensated by a reciprocal substitution at an interacting position. Such a coevolution scenario implies that the first mutation leads to a fitness reduction, while the compensating mutation restores it. Several methods have been developed to detect coevolving positions from sequence alignments. However, the validation of the resulting predictions relies so far only on indirect evidence such as residue contact maps in proteins for which an experimental structure is available. This study used the dataset that mapped substitutions for a protein sequence alignment on each phylogeny branch to detect coevolving amino-acids in bacterial homologous protein families (CoMap). Accounting for the biochemical properties of amino acids, we short-listed potential candidates from a dataset of thousands of coevolving groups for the experimental assessment. We then selected three candidate groups from three proteins (Elongation factor 4, IspH, and YebC proteins) displaying a pattern of co-substitutions in the \textit{Escherichia coli} branch of the phylogeny for charge and beta propensities for compensation. I experimentally reconstructed the local fitness landscape, resurrecting the ancestral genotype in \textit{E. coli} and putting it in competition with single mutants and reconstructed ancestral state (double mutant). I have performed competition experiments in LB Broth nutrient-enriched medium and M9 minimal (glucose as a single carbon source). In EF4 and YebC proteins, I observed a valley of lower fitness in single mutants in the local fitness landscape and restoration peak in the ancestral state. I report the first experimental assessment of the prediction of coevolution within a protein. I have also observed a peak in one of the single mutants of IspH candidates, which compensates for the charge only in one direction of the mutation. We used direct measurement of fitness estimation in \textit{E. coli} rather than using a proxy for fitness, \textit{i.e.}, protein fitness mentioned in most studies. The results of this study provide experimental evidence of the compensating nature in two out of three tested candidates, highlighting the potential of coevolution detection methods as tools to understand molecular evolution. This study helps to understand the interaction of the amino acids in the 3D space and can be used to predict the mechanism of evolution

Three Corporate Finance Practices in Pakistan: A Review of Previous Studies and Way Forward

This study reviews the previous empirical studies about the Pakistani capital market and specifies the pattern of three corporate finance practices. Various activities performed at the firm level such as capital budgeting, capital structure, and dividend payout policy are analyzed in the field of corporate finance. The capital budgeting technique consists of six methods, that is, net present value, discounted cash flow, payback period, and internal rate of return. However, Pakistani firms are often interested in the net present value and the internal rate of return for capital investment evaluation. Similarly, the capital structure decision carries the debate regarding two options of financing, that is, debt financing and equity financing, although the literature shows that the Pakistani firms generally follow the pecking order theory and prefer debt financing. Similarly, as for concern dividend payout policy, the extant literature discusses different theories and determinants although it is still not possible to generalize the dividend payout trend on its basis, specifically in the Pakistani context. Corporate managers and policymakers can use the conclusion of this study for strategic purposes

Vibration control of a two-story base-isolated building using a new tuned mass multi-sliding friction damper

This paper studies the use of a new Tuned Mass Multi-Sliding Friction Damper (TMMSFD) to increase the damping capacity of seismic isolators installed on a two-story base-isolated building to limit their lateral deformations. The proposed TMMSFD consists of a set of several masses that are laterally attached to the superstructure floor through linear springs. These masses are placed on top of each other one by one and are allowed to slide with respect to each other during the earthquake. The bottom mass that carries the weight of upper masses is in contact with the superstructure floor. The damping of system is supplied by the friction generated along the sliding friction surfaces. The TMMSFD has a low cost of installation, operation, and maintenance compared to common TMDs that use viscous fluid dampers for energy dissipation. The mechanical model of TMMSFD is installed on the numerical model of a two-story base-isolated building equipped with elastomeric rubber bearings in order to evaluate its performance in limiting the displacement of base floor. These models are created by the OpenSEESPy package which is a Python 3 interpreter of OpenSEES. A parametric study is performed to obtain the optimum design parameters of the TMMSFD including its total mass, frequency, and static friction coefficients of the siding surfaces for energy dissipation. The results of time-history analysis of numerical model show that the TMMSFD is capable of limiting the displacement of base floor with a little amount of friction implying its potential as a cost-effective tool for seismic protection

Endophytic Potential of Entomopathogenic Fungi for the Remediation of Wastewater

Phytoremediation has the potential to significantly reduce water contamination caused by excessive harmful chemicals. The degradative properties of fungi are used in fungal phytoremediation to eliminate or neutralise the hazardous pollutants present in water. The goal of the current study was to endophytize water lettuce with the two entomopathogenic fungus Metarhizium anisopilae and Trichoderma harazium. The plant is inoculated with the fungus using the root-dipping procedure. There were two main treatments and a control all with five replications. The analysis of plant and wastewater were analyzed initially like frequency of fungus remained in plant weight, root length and for water that was Biological oxygen demand (BOD), Chemical Oxygen demand (COD), and heavy metals (Copper, Nickle, Zinc and Cadmium). The data were taken for 3rd 5th and 7th day of the experiment. The results exhibit that T. harazium exhibited the 82.67 % followed by the M. anisopilae with 65.33 % as compared to control with 1.33 % mean frequency the 10th day of inoculation. Maximum weight 295.98 and 265.13 g and root length were maximum recorded 15.18 and 18.12 cm respectively at the end of the experiment. Performance of T. harazium endophytic plant found to be 90.7 % for BOD, 73.82 % for COD. The removal % of Cu, Zn, Ni, Cd exhibited 75.13, 96.58, 87.14, 61.17 % after 7d of treatment. In case of M. anisopilae, 85.2 % for BOD, 69.38 % for COD. The removal % of Cu, Zn, Ni, Cd exhibited 66.48, 89.43, 77.42, 52.4 % after 7d of treatment. The treatments exhibited the remarkable reduction in pollutants and increase in plant weight and root length

Efficient free radical scavenging activity of Ginkgo biloba, Stevia rebaudiana and Parthenium hysterophorous leaves through DPPH (2, 2-diphenyl-1-picrylhydrazyl)

Free radical scavenging activity of three important plants Ginkgo biloba, Stevia rebaudiana and Parthenium hysterophorous was carried out to evaluate and explore new potential sources of natural antioxidants. For this purpose the leaves of the three plants were processed. In these experiments the order of the antioxidant activity was, maximum activity shown by methanolic extract of Ginkgo biloba followed by Parthenium hysterophorous and Stevia rebaudiana. Furthermore the ethanolic extract of Ginkgo biloba also showed maximum antioxidant activity seconded by Stevia rebaudiana and Parthenium hysterophorous.Keywords: Ginkgo biloba, Stevia rebaudiana and Parthenium hysterophorous, DPPH, radical scavenging activit

Impact of Firm Reputation on Firm Financing Decision: Evidence from Non-Financial Sector of Pakistan

Research aims: Literature vows that firm reputation plays dynamic contribution in corporate financing decision. In line with findings of previous studies, this research explores the participation of firm reputation in firm financing specifically in Pakistani non-financial sector data set. Design/Methodology/Approach: Fixed effect model (FEM) applied to check the regression among the variables. Research findings: Findings signify the impact of firm reputation on firm financing decision. The price-earnings (P/E) ratio affiliates positively and significantly with firm financial leverage because an increment in price-earnings (P/E) ratio increases stability of firms. There exists negatively and significantly association between firm age and firm financial leverage due to decreases in usage of financial leverage with the passage of time. The firm age links negatively and significantly with trade-credit because older firms do not desire to use trade-credit. Moreover, assets tangibility has positive and significant impact on trade-credit because tangible assets work as loan collateral to get trade-credit. Policy implication: The study reveals the importance of firm reputation in firm financing decision and it gives financing policy to finance managers, that they can use reputation as an instrument of financing.  Firm reputation can help to secure the financial future of firm by mitigating the problem of stringent covenants. Limitations and future research: The time constrains and data shortage problem were faced by conducting this research and missed information of variables from balance sheets and income statements. The further study can be conducted in future by equipping all proxies of firm reputation of FMAC (Fortune Magazine’s Most Admired Companies) list and their effect on other business decisions i.e. investment and borrowing capacity

Prevalence of body-focused repetitive behaviors in three large medical colleges of Karachi: a cross-sectional study.

Background: Body-focused repetitive behaviors (BFRBs) that include skin picking (dermatillomania), hair pulling (trichotillomania) and nail biting (onychophagia), lead to harmful physical and psychological sequelae. The objective was to determine the prevalence of BFRBs among students attending three large medical colleges of Karachi. It is imperative to come up with frequency to design strategies to decrease the burden and adverse effects associated with BFRBs among medical students. Methods: A cross-sectional study was conducted among 210 students attending Aga Khan University, Dow Medical College and Sind Medical College, Karachi, in equal proportion. Data were collected using a pre tested tool, “Habit Questionnaire”. Diagnoses were made on the criteria that a student must be involved in an activity 5 times or more per day for 4 weeks or more. Convenience sampling was done to recruit the participants aged 18 years and above after getting written informed consent. Results: The overall prevalence of BFRBs was found to be 46 (22%). For those positive for BFRBs, gender distribution was as follows: females 29 (13.9%) and males 17 (8.1%). Among these students, 19 (9.0%) were engaged in dermatillomania, 28 (13.3%) in trichotillomania and 13 (6.2%) in onychophagia. Conclusions: High proportions of BFRBs are reported among medical students of Karachi. Key health messages and interventions to reduce stress and anxiety among students may help in curtailing the burden of this disease which has serious adverse consequences

An Analysis of the Relationships among Exports, Imports, Physical Capital and Economic Growth in Pakistan

This review emphasized the relationship among capital formation, economic growth, exports and imports in case of Pakistan scenario using time series data from 1976 to 2015. Augmented Dickey Fuller Test, Johansen Co-integration, Vector error correction model and Granger Causality techniques have been used to check the relationships among exports, imports and economic growth. The results from this study show that the exports, imports, real GDP and gross fixed capital formation have a long run relationship and are co-integrated. This study uses the data of Pakistan and concludes that GDP doesn’t granger cause with the export and import while export and imports do granger cause with the GDP in the long run. Finding of the study also displays that physical capital formation has no impression over GDP. Previous study shows the positive relation among exports, imports, capital formation and economic growth while this study shows that in the long run capital formation and economic growth has no effect. Government subsidizes the exports and also increases the duty bills on imports that help boost the domestic industries manufacture the goods and motivate to produce the best quality of goods. JEL codes: F2, O4