Identification of predictive biomarkers of resistance to radiotherapy in rectal cancer

Introduction and Aims:Neoadjuvant radiotherapy (RT) provides local control of disease in rectal cancer, however, the ability to predict response to RT is limited. The aim of this study was to establish a novel radioresistant (RR) rectal cancer cell line model and identify putative biomarkers of radioresistance using a microarray-based comparative proteomic platform.Methods:The inherent radiosensitivity of SW-837 and HRA-19 rectal adenocarcinoma parental cells was initially assessed. Following irradiation at 0, 2, 4, 6, 8 and 10 Grey (Gy) single doses using a linear accelerator, modified colony counting assays were performed. Dose response curves (DRCs) were plotted from calculated survival fraction (SF) values. To induce radioresistance, parental SW-837 and HRA-19 cells were irradiated in 8 and 4 Gy fractions, respectively, to a total dose of 48 Gy to generate novel sub-lines (termed SW-837 RR and HRA-19 RR). Following comparison of the DRCs from untreated parental cells and novel RR cells, total protein was extracted from radiosensitive parental (PN) cells and novel RR cells. Protein lysates from respective PN and RR cells were co-incubated onto Panorama antibody microarray (AbMa) slides containing 725 antibodies. Proteins which demonstrated at least 1.8-fold difference in expression between PN and RR cells were considered significant. The proteins with consistent differential expression and a putative role in radioresistance were selected for validation by immunohistochemistry (IHC), as a pilot study, in an archival series of 33 rectal cancer tissues categorised into ‘good response’ and ‘poor response’ groups based on tumour regression grading following long course chemoradiotherapy.Results:The comparison of DRCs revealed SW-837 RR cells to be significantly more radioresistant at 4, 6, 8 and 10 Gy and HRA-19 RR cells at 4, 6 and 8 Gy single doses than their respective parental cells (p<0.05). Comparative AbMa analyses of respective PN and RR cells demonstrated 62 differentially expressed proteins (DEPs) common to both RR cell lines. Of these, two apoptosis related proteins - DR4 and Bcl-2 were chosen for preliminary immunohistochemical validation for their putative role in radioresistance. The DR4 protein was found to be equally expressed whereas Bcl-2 demonstrated a trend towards reduced expression in 'poor-responder' rectal cancers compared with 'good-responders' that was not statistically significant.Conclusions:A radioresistant rectal cancer model consisting of novel SW-837 RR and HRA-19 RR cell sublines was successfully established and comparative proteomic analysis revealed a number of DEPs. In a small pilot IHC study, initial validation experiments showed no significant expression difference for DR4 and Bcl-2 proteins between ‘poor-responder’ and ‘good-responder’ rectal cancer patients. A panel of novel biomarkers from antibody array data would require further validation to determine their association with radioresistance before any firm conclusions can be drawn

Towards Building Blue Life Science Economy

The overexploitation and lack of land resources have compelled marine governments to rely on the oceans for economic prosperity. The term for this notion is "the blue economy." As a case study, the subject research focuses on the significance of changing from a green economy to a blue economy while stressing Pakistan's blue economy's potential and problems. Pakistan has failed to maximize the use of its abundant resources. Due to several obstacles confronted by Pakistan, the blue economy's resources are not being harnessed, as indicated by the data gathered throughout this topic study. This is a fallacy; in reality, these obstacles are already being overcome. The underlying reason these resources are not being utilized is a lack of will at all levels. Lack of nautical expertise and the capacity to see the sea, or "sea blindness," is seen to be the biggest obstacle to the development of Pakistan's marine industry. Islamic nations must agree on a plan to move from the Green Economy to the Blue Economy so that musharka, ijar, and sukuk can be used to meet future needs.                                      Keywords: Pakistan; Blue econom

Marine Life & Fish Management an Effective Tool of Blue Economy of Pakistan

Currently, all fishery-related operations in Pakistan are handled by four major fish harbors: Karachi Fish Harbor, Korangi Fish Harbor, Pasni Fish Harbor, and Gwadar Fish Harbor. Pakistan's fishing communities are not only home to generations of people who have relied on the industry to make a living, but also to a wealth of natural beauty. However, with a growing population comes a rise in demand, and as supplies dwindle, so does the world's ability to feed its people. It's a similar story in marine fisheries, where declining interest from local and foreign corporations and the use of antiquated methods of fishing have made it difficult for fishermen to earn a livable wage.                          Keywords: Fish harbor; Pasni; Gwadar; Korangi; Karachi; Fisher

Relationship of Anthropometric Indices of Obesity with Arterial Stiffness and Blood Pressure

To determine the comparison and relationship of anthropometric indices with blood pressure and arterial stiffness index (ASI) in normotensive, prehypertensive and hypertensive male adults.Methods: In this randomized case control study ninety male subjects between 35-55 years of age were selected with each group comprising of thirty normotensive, pre-hypertensive and hypertensive subjects. According to the World Health Organization (WHO) guidelines their height, weight, hip (HC) and waist circumferences (WC) were measured. Waist hip ratio (WHR), body mass index (BMI), conicity index (CI) and waist stature ratio (WSR) were calculated. Blood pressure (BP) was measured by mercury sphygmomanometer with auscultatory method. Photoplethysmography was done by placing velcro scrap on volar surface of middle finger and digital volume pulse (DVP) was recorded with iWorx-214 physiological interface system and ASI was calculated. Statistically, difference amongst the three groups was determined by applying one way ANOVA. Difference between the groups was analyzed by Post Hoc Tukey’s test. Pearson’s correlation coefficient was calculated to study the relationship. p-value&lt;0.05 was considered significant.Results: There was statistically significant difference in WC (0.003), WHR (0.0001) and ASI (0.0001) between the three groups but not BMI (0.223). Amongst the anthropometric measurements, WC and WHR were positively correlated to the systolic and diastolic blood pressure.Conclusions: Central obesity is better predictor of arterial stiffening and hypertension than BMI

Solar-driven absorption cooling system with latent heat storage for extremely hot climates

Novel renewable cooling systems are required worldwide to address the growing demand for cooling. This study proposes and demonstrates a novel integration of solar-driven absorption cooling with latent heat storage to maximise the use of renewable energy for cooling in extremely hot climates. A parametric analysis was performed in TRNSYS to identify the critical parameters for optimal sizing related to the solar field size, tank volume, tank insulation, auxiliary heating set point, and collector tilt angle. Moreover, the integration was compared with a conventional solar-driven absorption cooling system using sensible heat storage (a hot water tank) and an electric-driven vapour compression cooling system. The results show that a solar field size of 1.5 m2/kWc, a latent heat storage tank volume of 30 L/m2, adequate insulation below 0.8 W/m2.K, and appropriate set-point temperatures for the auxiliary boiler provide the optimal performance to maximise the solar fraction. Compared with conventional solar-driven absorption cooling, the study demonstrates how the phase change material (PCM) increased the solar fraction by 4.2 % (from 70.3 to 74.5 %) due to higher stable temperature and lower tank losses (reduced by 44 %). In addition, despite the higher initial investment cost of the proposed PCM-based solar-driven cooling system compared to the vapour compression cooling system, the findings highlight that the life cycle cost is much lower in extremely hot climates. After 25 years, the life cycle cost was lowered by 34 % compared to vapour compression and by 9 % compared to a conventional solar-driven cooling system. Compared to vapour compression refrigerant technology, the proposed system can save 31.6 % of primary energy and 1222 kgCO2eq annually. This research provides valuable insights into the optimal design and integration of renewable cooling for residential applications in extremely hot regions

COMPARISON OF READING ALOUD STRATEGIES VERSUS SILENT READING STRATEGIES USED ON PAKISTANI UNIVERSITY STUDENTS’ READING COMPARISON FOR READING PROFICIENCY & LITERAL READING SKILLS

Reading is the best way to give knowledge. Reading is an essential part of learning. No one can neglect its importance. There are many strategies for reading. Among them, one is silent reading strategy while another one is reading aloud strategy. Pakistan is a developing country where the English language is used as a second language because the national language is Urdu. Students’ base for English conversation and writing is poor in such condition reading aloud strategy is important especially for poor readers. No one can neglect its importance, and that is why the importance of read-aloud strategy is increasing as compared to silent reading strategy. The present study was conducted in a Pakistani university. A comparative analysis of read-aloud strategies versus silent reading strategies was done. Data was collected from M.Phil. Masters, and BS program students through questionnaires. The study is based on an experimental and questionnaires were used, the targeted sample was from English department in which 20 students and teachers of BS program were selected while 170 respondents including 100 male and 70 female were selected for the questionnaire. Findings show that read aloud strategies is better than silent reading because in Pakistan English language used as a second language. Students had shown a better response for reading aloud strategies for reading proficiency and literal reading skills.  Article visualizations

Low-energy resilient cooling through geothermal heat dissipation and latent heat storage

Conventional passive cooling techniques provide limited benefits in extremely hot climates in southern Asia, characterised by high daytime and night temperatures and frequent climate-related disruptions, such as power cuts. This study proposes and demonstrates a novel low-energy and resilient cooling solution for extremely hot regions in southern Asia. The novelty lies in the combination of geothermal heat dissipation and latent heat storage, specifically designed for the particular conditions of extremely hot climates in Southern Asia; considering the influence of climate-related disruptions such as power cuts, whose frequency is increasing in the region; and using discomfort hours as an indicator to measure the passive survivability of buildings in the absence of air-conditioning (following the adaptive comfort model). A numerical model was developed in TRNSYS for optimal sizing and configuration of the phase change material (PCM) integrated into a ceiling panel using a typical multi-family building archetype in three climatic regions of Pakistan. A parametric numerical analysis was performed concerning different PCM melting temperatures, amount of PCM, convective heat transfer capacity, and equivalent thermal conductivity. Moreover, daytime was considered the period with a higher probability of power cuts. The results showed how integrating PCM-based ceiling panels with geothermal heat dissipation can mitigate discomfort hours by 28 % in extremely hot climates, 55 % in very hot climates, and 91 % in hot climate areas with intermittent access to electricity. Latent heat storage maximised the benefits of geothermal heat dissipation by extending thermal comfort periods by 13 % and 18 % in extremely hot and very hot climates compared to the scenario without PCM. This low-energy resilient cooling solution, integrating PCM as a cool battery, can keep the home cool for longer when electricity is unavailable. This study demonstrates the importance of considering the specific climate-related disruptions from these extremely hot regions in building design, such as extreme heat events or power cuts, to enhance the heat resilience capacity of cities

Impact of CPEC on Pakistan’s Economic Outlook

Pakistan‟s vital geopolitical position is an advantage for this South Asian nation. It is located at the apex of the Arabian Peninsula. Thus, the People‟s Republic of China has setup the Belt and Road Initiative (BRI) with a futuristic strategy to gain long-term benefits. This planning is not random at all. It is a cohesive plan to revitalize the financial system of its long-standing collaborator and ally through the China-Pakistan Economic Corridor (CPEC) which is currently the talk of the town. The present study analyzes how Pakistan‟s conventional economic outlook can be transformed through the CPEC. While harnessing the power of Pakistan as a &bdquo;trade route‟, the CPEC has the potential to reshape transport &amp; security options, increase the cost-effectiveness of goods, and widen the scope for new and existing businesses. it will develop a networking coherence among agricultural &amp; industrial hubs and connect special economic zones (SEZs) with the rest of the country and beyond. This paper evaluates the CPEC‟s fiscal footprint on Pakistan‟s economy and examines the correlation between overcoming economic shortcomings and increasing future gains through a cause-and-effect relationshi

The impact of human capital outsourcing on human capital management practices in Karachi pharmaceutical industry

Purpose: The aim of this research is to examine relationship between Human Capital Management (HRM) and Human Resource (HR) Outsourcing in the Pharmaceutical sector. The specific objective is to find out that how important is HRM for an Organization to perform its operations more efficiently, and at what level Human Resource Outsourcing is affecting it. Literature review: Literature review shows that HR outsourcing has positive impact on HRM for an Organization to perform its operations more efficiently. Methods: In order to conduct this research the methodology that has been used is quantitative in nature and closed ended Questionnaire was used to collect data. The universe of study was the employees of Pharmaceutical industry in Karachi Pakistan. The responses of each respondent were thoroughly analyzed by using SPSS software, and the results show that there is a negative relationship between the Human Capital Management (Gaining Knowledge, Current Trend of Business Environment, Organization Managing Their Human Asset and Practices and Policies Regarding Human Resource) and HR Outsourcing. Conclusions: It is concluded that all Independent Variables have the strongest Positive correlation with each other. There are lots of constraints, which any organization faces in terms of time, finance and, in some cases factors like strategic focus.Human Capital Management, Karachi, Pharmaceutical, Outsourcing