502 research outputs found
Synthesis and Biological Evaluation of Chalcone Scaffolds as Potential Antiangiogenic Agents.
Get PDFAngiogenesis is an integral part of tumour growth and development. Endothelial cell proliferation, migration and differentiation are the main hallmarks of this physiological process. From this, the use of antiangiogenic therapy have brought about a range of licensed FDA approved agents (that are also used by the NHS), that aim to regress tumour induced angiogenesis. However, issues such as: drug resistance, evasion and poor efficacy have limited the use of antiangiogenic therapy as a main stake in anti-cancer therapy. The need for multi-targeted or combinatorial therapies are ever more needed to enhance the current use of these drugs. Therefore, in an attempt to identify novel compounds that exhibit antiangiogenic activity, a group of 1-3-diphenylpropenones (chalcones) were designed, synthesised and biologically evaluated using AH1 (2-chloro-2’5’-dihydroxychalcone) as the parent compound. Methods: Chalcones were synthesised using variations of the Clasien-Schmidt condensation reaction, to develop a compound library based on AH1 (the parent compound). Thereafter, using HUVECs as an angiogenesis model, the effects of the compounds on HUVEC proliferation and migration were evaluated. This was carried out using the MTT cell proliferation assay and the wound healing “scratch” assay. Therein mechanistic evaluation was carried via gel electrophoresis and chemiluminescence western blot. Main findings: Structure activity relationships (SARs) studies identified, that novel compounds AH9 (2-bromo-2’5’-dihydroxychalcone) and AH12 (2-nitro-2’5’-dihydroxychalcone) were shown to exhibit strong anti-proliferative activity along with AH1. Other synthesised derivatives containing different functional groups such as, alkoxy, halogen and methyl did not exhibit similar activities to AH1. The culmination of structure activity relationship suggested that 2’5’-dihydroxy moiety was important to the observed activity only in conjunction with 2-chloro or now 2-bromo substitution on the other phenyl ring. Due to AH9’s better drug likeness over AH12, AH9 and AH1 were taken forward as the lead candidates. Anti-migratory analysis of lead candidates and licensed drug Sorafenib were conducted against HUVECs. AH9 (p < 0.0007) was shown to exhibit significantly more potent inhibitory effects on endothelial migration than AH1 (p = 0.19) and Sorafenib (p = 0.41) over the 8 hour time course study when compared to the untreated control. Mechanistic evaluation identified that AH9 could be exerting its anti-proliferative and potent anti-migratory activity via inhibiting ERK kinase phosphorylation, this was seen at 10μM (p < 0.0001). Discussion and conclusion: To summarise, anti-proliferative and potent anti-migratory activity, towards HUVECs, of a
novel molecule AH9 have been identified showing significant effects against two hallmarks of the angiogenesis cascade. AH9 presents a strong case as an agent capable of being developed as an angiogenesis inhibitor for anti-angiogenic therapy
Alarming Scarcity of Blood Donations
Get PDFHuman blood is a unique and specialized tissue.Screening of blood donation products have beenincreasing in the community before usage. However,on the con side “Blood Donation Practices” aredecreasing in the society. WHO blood donationsrecommendationfor low-income countriesare 20/1000population, at minimum level. Currently, this rate ishighin high-income countries (38/1000 population) and lowin low-income countries(4/1000 population). Accordingto WHO recent report, out of about 100 million blooddonations, nearly more than half donations are dulyneeded by children under the age of five years,amonglow-income populations. On the contrary, among thehigh-income populations, this ratio(approximate 75%)is shifted to older than 65 years of age.1There is cleartrend of boost in the demand of blood donations as thenumber of surgeries, neurological and blood carcinomasrelated palliative treatments as well as old age populationare growing day by day.To cope up these, there is veryscarce supply of blood donations in the healthcaremarket.2Even unethical blood donations like paid donorsnot able to cut these high demands down. Drasticallythey are increasing the burden of infections risks oftransfusion related serious transmitted infections forinstance HIV, Syphilis
Trade Openness and Growth: An Analysis of Transmission Mechanism in Pakistan
Get PDFThis paper investigates the linkages between trade policy openness and economic growth for Pakistan for the period 1973 to 2008. The paper tests the hypothesis that trade policy does not affect economic growth directly rather it affects through some growth determining economic variables, which then effect economic growth. For this purpose a simultaneous system of equations is estimated through the Three Stage Least Squares. The results suggest a positive impact of trade policy openness on Black Market Premium, Domestic Investment and Foreign Direct Investment (FDI) and negative impact on Macro Policy Index. However, Black Market Premium and FDI show negative and Domestic Investment shows positive impact on economic growth.Openness, Growth, Transmission Mechanism, Pakistan
Pro-poor intervention strategies in irrigated agriculture in Asia: poverty in irrigated agriculture: issues and options: Pakistan
Get PDFIrrigated farming / Poverty / Irrigation management / Irrigation systems / Water policy / Water rights / Water law / Irrigation scheduling / Organizations / Social aspects / Households / Economic aspects / Expenditure / Irrigation programs / Performance evaluation / Water delivery / Equity / Models / Crop production / Productivity / Wheat / Pakistan
Earnings Per Share Versus Cash Flow Per Share as Predictor of Dividend; Evidence from Non Financial Sector of Pakistan
Get PDFThis research study has compared the relative predictive power of earnings and cash flow in order to find out the best predictor of dividend. This study has used panel data techniques and the data has been collected from the balance sheet analysis of 104 KSE-100 index non-financial companies. This study has employed a linear mixed effect model approach to investigate the main problem. The two models (earnings based model and cash flow based model) have been compared by using log likelihood estimator and Akaiki information criteria (AIC). The results have shown that cash flow per share is a better predictor of dividend than earnings per share in term of log likelihood estimator and Akaiki information criteria (AIC). The results have also concluded that both earnings per share and cash flow per share have a significant relationship with dividend. The study also finds out that all the control variables including firm’s size (SIZE), leverage ratio (LR), market to book value (MBV) and liquidity ratio (LIQ) have a significant relationship with dividend. Keywords: Earning per share (EPS), Cash flow per share (CFPS), Dividend, Linear mixed effect model, Log likelihood estimator, Akaiki information Criteria (AIC) and KSE-100 inde
SAUDI-IRAN RAPPROCHEMENT AND CHALLENGES FOR PAKISTAN
Get PDFSaudi-Iran relations have been continuously evolving, with regional and global implications. Though religious differences make up a large part of this relationship, it is not all. Multiethnicity, Arab versus Persian domination, and divergence of interests of regional and extra-regional players are also significant. The two regional heavyweights have driven the neighbouring states towards alliances of varying natures. It has repercussions for Pakistan due to its security, economic concerns, and religious and sectarian fault lines. Opportunely, the current political environment is developing prospects to rebuild relations. After unfinished rapprochement efforts by Pakistan, Iraq has recently made the latest endeavour of arbitration. This paper analyses the effects of the Saudi-Iran contention on Pakistan and the scope and implications of the current rapprochement effort. Primarily, the qualitative method has been used, and it has been established that due to the complexities of a relationship, achieving peace is not as easy as it appears. Also, from Pakistan’s perspective, escalation levels should ideally remain below the threshold of a dispute necessitating precise positions and above a minimum threshold of complete peace to keep Pakistan’s security-related relevance. Therefore, diplomatic efforts should be limited to de-escalating conflicts rather than mediating them.Â
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Bibliography Entry
Saleem, Aamir, and Syed Mussawar Hussain Bukhari. 2022. "Saudi-Iran Rapprochement and Challenges for Pakistan." Margalla Papers 26 (1): 98-107
Climate Change and Drought: Impact of Food Insecurity on Gender Based Vulnerability in District Tharparkar
Get PDFClimate change has now become a reality that has intensified
the sufferings of people living in arid ecosystems. Decrease in
rainfall, rise in temperature and increase in the frequency of extreme
events are some of the changes observed in the semi-arid desert of
district Tharparkar. For thousands of years, people of Tharparkar are
coping with drought and aridity of the land by using indigenous
knowledge. However, global changes in the climatic pattern and
deterioration of social and economic conditions have pushed the
inhabitants of this arid region into extreme vulnerable situation. This
paper investigates the link between climate-induced natural disasters,
particularly drought, from the perspective of changing climate patterns
which have resulted in food insecurity and water scarcity. The paper
analyses the rainfall pattern in the last 38 years—dividing it into two
periods i.e. from 1975-1994 and 1995-2014. The findings of the paper
have challenged the prevailing notions about aridity and rainfall
patterns in Tharparkar district. The research found that there is an
increase in average annual precipitation in the district with erratic
patterns. Thus, the nature of drought in the district has changed from
its historic pattern of less or no rainfall to more but erratic rainfall
that is more threatening to livelihoods of the people that in turn have
multiplier effect on water and food insecurity. In particularly, women
are more vulnerable in the absence of social security and lack of basic
necessities for their survival amidst drought. For instance,
traditionally the burden of managing water resources falls on women,
which leads to an increased work load during the time of drought and
also water scarcity. JEL Classification: Q54, Q56, Q25, I30 Keywords:
Climate, Environment and Development, Drought, Water, Povert
Bayesian Heuristics for Robust Spatial Perception
Full text linkSpatial perception is a key task in several machine intelligence applications
such as robotics and computer vision. In general, it involves the nonlinear
estimation of hidden variables that represent the system's state. However, in
the presence of measurement outliers, the standard nonlinear least squared
formulation results in poor estimates. Several methods have been considered in
the literature to improve the reliability of the estimation process. Most
methods are based on heuristics since guaranteed global robust estimation is
not generally practical due to high computational costs. Recently general
purpose robust estimation heuristics have been proposed that leverage existing
non-minimal solvers available for the outlier-free formulations without the
need for an initial guess. In this work, we propose three Bayesian heuristics
that have similar structures. We evaluate these heuristics in practical
scenarios to demonstrate their merits in different applications including 3D
point cloud registration, mesh registration and pose graph optimization. The
general computational advantages our proposals offer make them attractive
candidates for spatial perception tasks.Comment: 10 pages, 8 figure
An Ethnobotanical Survey of Important Wild Medicinal Plants of Hattar District Haripur, Pakistan
Get PDFAn ethnobotanical survey was undertaken for the purpose of collecting information from traditional healers on the use of medicinal plants in Hattar region, District Haripur, NWFP, Pakistan during 2004-06. The indigenous knowledge of local traditional healers and the native plants used for medicinal purposes were collected through questionnaire and personal interviews during field trips. Plants with their correct nomenclature were arranged alphabetically by family name, vernacular name and ethnomedicinal uses. The identification and nomenclature of the listed plants were based on The Flora of Pakistan. Hattar was surveyed 2-times per year comprising autumn and spring season. A total of 45 plants species were identified by taxonomic description and locally by folk knowledge of people existing in the region. Out of 45 plant species, 17 were perennials/biannual, 20 were found in spring, while 8 species were found in autumn season. Plant specimens collected, identified, preserved and mounted were deposited in the Herbarium, Qarshi Herb Centre, Hattar, Haripur for future references
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