Muhammad Tariq

Modeling surface water quality using soft computing techniques is essential for the effective management of scarce water resources and environmental protection. The development of accurate predictive models with significant input parameters and inconsistent datasets is still a challenge. Therefore, further research is needed to improve the performance of the predictive models. This study presents a methodology for dataset pre-processing and input optimization for reducing the modeling complexity. The objective of this study was achieved by employing a two-sided detection approach for outlier removal and an exhaustive search method for selecting essential modeling inputs. Thereafter, the adaptive neuro-fuzzy inference system (ANFIS) was applied for modeling electrical conductivity (EC) and total dissolved solids (TDS) in the upper Indus River. A larger dataset of a 30-year historical period, measured monthly, was utilized in the modeling process. The prediction capacity of the develo...

Alzheimer’s disease (AD) causes dementia and continuous damage to brain cells. Cholinesterase inhibitors can alleviate the condition by increasing communication between the nerve cells and reducing the risk of dementia. In an effort to treat Alzheimer’s disease, we synthesized flurbiprofen-based diamines (1,2 diaminoethane and 1,3 diaminopropane) Zn(II), Cu(II) metal complexes and characterized them by single-crystal X-ray analysis, NMR, (FT)-IR, UV-Vis, magnetic susceptibility, elemental analysis and conductivities measurements. Synthesized diamine metal complexes appeared in ionic forms and have distorted octahedral geometry based on conductivity studies, magnetic susceptibility and electronic studies. Single crystal X-ray diffraction analysis confirmed (2b) Cu(H2O)2(L1)2(L2)2 complex formation. Moreover, we tested all synthesized metal complexes against the cholinesterase enzyme that showed higher inhibition potential. In general, copper metal complexes showed higher inhibitory a...

Synthesis of C-2 N-substituted anthranilamide derivatives was carried out in a straight forward manner, utilizing 2-aminobenzamide and benzyl chloride as starting materials. Their crystal structures have been established by single crystal X-ray crystallographic method. In the molecules of 2-benzylamino-benzamide (3a), intramolecular hydrogen bonding b/w O atom and proton of –NH and classical intermolecular hydrogen bonding of the type N–H · · · O forming eight membered rings in R42(8) pattern. In both molecules of 2-(dibenzylamino)benzamide (3b), unlike the molecule in 3a, each H atoms is pointed towards N atom causing intramolecular hydrogen bonding interactions, resulting in S(6) motifs. However, it is interesting to note that both molecules in 3b are lying about inversion centres and form dimers in R42(8) motifs; the two dimers are linked via non-classical intermolecular hydrogen bonds C–H · · · O resulting in clusters of four molecules in the structure. In vitro assay results re...

Few data exist in the literature regarding outcomes of men with prostate cancer (CaP) who are receiving immunosuppression from prior organ transplantation. The aim of this study was to evaluate biochemical disease-free survival, distant metastasis-free survival, overall survival, and toxicity in patients with organ transplants who were later treated with definitive radiotherapy for CaP. Our institutional CaP registry was reviewed to identify patients who had undergone an organ transplantation before CaP diagnosis. Between 1999 and 2013, a total of 28 organ transplant recipients treated with definitive radiotherapy for CaP were identified. Treatment consisted of either I-125 low-dose-rate brachytherapy or external-beam radiotherapy. All patients were receiving immunosuppressive medications. The median age was 66 years. Median follow-up time was 30 months. Twenty-four patients (86%) were treated with brachytherapy, and 4 patients (14%) were treated with external-beam radiotherapy. Nine patients (32%) had low-risk CaP, 14 (50%) had intermediate-risk CaP, and 5 (18%) had high-risk CaP. At the time of last follow-up, 2 patients had died, 1 from metastatic CaP and 1 from other causes. The 3-year biochemical disease-free survival was 95.8%. The 3-year distant metastasis-free survival was 93.1%. The 3-year overall survival was 93.8%. One patient developed grade 3 late gastrointestinal toxicity. This represents one of the largest reported series of outcomes in patients with organ transplantation and CaP. Organ transplant recipients treated with prostate radiotherapy have excellent 3-year outcomes.

Gastric cancer is one of the most prevalent tumor types in the world. Chemotherapy is the most common choice for cancer treatment. However, chemotherapy resistance and adverse side effects limit its clinical applications. Aberrant expression of long noncoding RNAs (lncRNAs) has been found in various stages of gastric cancer development and progression. In this study, we identified that an oncogenic lncRNA, long intergenic non-protein-coding RNA D63785 (lncR-D63785), is highly expressed in gastric cancer tissues and cells. Silencing of lncR-D63785 inhibited cell proliferation, cell migration and invasion in gastric cancer cell lines and reduced tumor volume and size in mice. We found that the expression of lncR-D63785 was inversely correlated with microRNA 422a (miR-422a) expression, which was involved in the downregulation of expression of myocyte enhancer factor-2D (MEF2D) and drug sensitivity. Knockdown of lncR-D63785 increased the expression of miR-422a and the sensitivity of gas...

Waardenburg syndrome (WS) is a rare genetic disorder. It is caused by multiple mutations affecting the melanocytes, leading to a multitude of skin, hair, and eye symptoms. It is an autosomal dominant disease with four subtypes, each presenting with varying degrees of sensorineural hearing loss along with a constellation of other symptoms. Hirschsprung disease is unique to Waardenburg-Shah syndrome subtype 4 and is not associated with any other subtype. We present a case of this subtype 4 that presented with a bilateral sensorineural hearing loss, mutism, delayed milestones, white forelock, Hirschsprung disease, and bilateral blue homochromatic irises, a finding which is not typical for this subtype. This is the first case of WS with homochromatic irises and the fourth case to be reported from Pakistan.

The prolonged use of levodopa for treating Parkinson's disease is associated with motor and nonmotor complications. These include wearing-off, delayed-on, partial-on, no-on, and on-off phenomena. In the wearing-off effect, symptoms return before a patient's next scheduled dose of levodopa. Patients may present with motor, sensory, or autonomic fluctuations. In this report, we present a female patient experiencing numbness of lips and slurred speech as a symptom of wearing-off effect. The major differential for sudden numbness of lips and slurred speech includes transient ischemic attacks. Therefore, it is imperative to identify the cause of these episodes so that appropriate treatment can be initiated. Our patient underwent extensive cardiac and neurological investigations, the findings of which were unremarkable. Her symptoms were likely due to levodopa wearing-off. Her condition improved on changing her levodopa to a sustained release form with more frequent dosing along w...

Investigators are using checkpoint inhibitors (CPI) to treat aggressive hematologic malignancies before patients undergo allogeneic hematopoietic stem cell transplantation (allo-HSCT) and in some patients with relapsed disease after allo-HSCT. CTLA-4 inhibitors and PD-1 inhibitors are two main types of CPI, which work through activation of the immune system. On one hand CPI can achieve graft versus tumor (GVT) effect, and on the other hand there is risk of graft versus host disease (GVHD). After a comprehensive literature review we included data (n=283) from twenty-four studies (11 original manuscripts, 13 case reports or case series) and evaluated the results to assess the safety and efficacy of CPI use in conjunction with allo-HSCT. One hundred seven patients received CPI before allo-HSCT and one hundred seventy-six patients received CPI after allo-HSCT. The most common indication for CPI use was for Hodgkin lymphoma. The CPIs used in various studies included ipilimumab, nivolumab...

R-CHOP has been the standard of care for diffuse large B cell lymphoma (DLBCL), curing approximately 60% of patients for more than 2 decades. However, the optimal treatment of patients who are too frail to tolerate this regimen and/or are not candidates for anthracycline therapy continues to be debated. MInT and GELA trials established addition of rituximab to CHOP in DLBCL but excluded patients older than 80 years. Multiple regimens have been tried with varying success in the very elderly, including R-mini-CHOP, R-mini CEOP, R-split CHOP, pre-phase strategies, and R-GCVP. However, there has not been a randomized trial among these strategies. Although addition of novel agents including ibrutinib, brentuximab vedotin, lenalidomide, and many others on the horizon holds promise in this population, none have been tested in a randomized setting or have results awaited. There is also a lack of a validated and easy to use clinical tool in this population to predict patients who will not to...

The OrthoMiDaS (Orthopedic Minimal Data Set) Episode of Care (OME) database was developed in an effort to advance orthopedic outcome measurements on a national scale. This study was designed to evaluate if the OME data capture system would increase the quality of data collected in the context of primary and revision total hip arthroplasty (THA) compared to conventional operative notes. This study includes data from the first 100 primary THAs and 100 revision THAs performed by 15 surgeons at a single institution from January through April 2016. Surgeons prospectively entered procedural details into OME following surgery. The OME database and operative notes were compared to evaluate completion rates and agreement. Completion rates were compared using McNemar's test (with continuity correction), while agreement was analyzed using Cohen's kappa (κ) and concordance correlation coefficient. The OME database had significantly higher completion rates for 41% (39/96) of the variable...

Continuous assessment tests influence the learning needs of medical students at particular times but are also beneficial in scheduled learning, and act as motivating tool. These tests drive them to study by developing competition and optimism regarding the forthcoming result. This study has been designed to evaluate the role of these tests for medical students by learning about their motivation. This study was conducted on 150 medical students. The students selected a continuous testing system or a classical system. Those who selected the continuous system had six assessment tests each, after completion of a curriculum block, usually 45 days apart. The motivation of the students in both the groups was assessed by asking them for their expected results just before the final examination. Statistical analysis was performed using Superior Performance Statistical Software (SPSS) version 20. The students' final results showed that almost half of the students who adopted the continuous...

Coronary heart disease (CHD) is one of the leading disorders with the highest mortality rate. Percutaneous angioplasty and stent implantation are the currently available standard methods for the treatment of obstructive coronary artery disease. However, the stent being an exogenous substance causes several complications by promoting the proliferation of vascular smooth muscle cells, immune responses and neointima formation after implantation, leading to post-stent restenosis (ISR) and late thrombosis. The prevention of these adverse vascular events is important to achieve long-term proper functioning of the heart after stent implantation. Non-coding ribonucleic acids (ncRNAs) are RNA molecules not translated into proteins, theyhave a great potential in regulating endothelial cell and vascular smooth muscle function as well as inflammatory reactions. In this review, we outline the regulatory functions of different classes of ncRNA in cardiovascular disease and propose ncRNAs as new t...

Gastric cancer is one of the most common cancers and is the second leading cause of cancer mortality worldwide. Therefore, it is urgent to explore new molecular biomarkers for early diagnosis, early treatment and prognosis for gastric cancer patients. Recently, increasing evidence has shown that epigenetic changes, such as aberrant DNA methylation, histone modifications, and noncoding RNAs (ncRNAs) expression, play substantial roles in the development and progression of malignancies. Among these changes, long non-coding RNAs (lncRNAs), a novel class of ncRNAs, are emerging as highly versatile actors in a variety of cellular processes by regulating gene expression at the epigenetic level as well as at the transcriptional and post-transcriptional levels. Hundreds of lncRNAs become dysregulated in the various pathological processes of gastric cancer, and multiple lncRNAs have been reported to function as tumor-suppressors or oncogenes, although the underlying mechanisms are still under...

Routine preoperative blood testing has become a dogma. The general practice is to order preoperative work up as a knee jerk response rather than individualize it for each patient. The fact that the bleeding brain tends to swell, which coupled with limited options for proximal control, packing and overall hemostasis, leads to an over emphasis on preoperative coagulation profile. This is a retrospective review of the medical records of patients admitted at Aga Khan University Hospital from January 2010 to December 2015 for an elective craniotomy. The hospital registry was used to identify files for review. Data was collected on a predefined proforma. A nationwide survey was performed and 30 neurosurgery centers were contacted across Pakistan to confirm the practice of preoperative workup. The survey revealed that all centers had a similar practice of preoperative workup. This included CBC, serum electrolytes and coagulation profile; including PT, aPTT and INR. A total of 1800 files we...

To determine the effect of lower limb ergometric training on echocardiographic parameters of left ventricle in dilated cardiomyopathy (DMC) patients. Randomized control trial. Rawalpindi Institute of Cardiology, Rawalpindi, Pakistan, from September 2016 to February 2017. Clinically stable patients with DCM (n=60), were randomly allocated into an interventional group with two-month interventional program and a non-trained control group (n=30 each). Treatment protocol for interventional group was lower limb ergometer exercise for 8 weeks, 4 days/week. Pre and post-treatment echocardiography was done in both groups at baseline and after 8 weeks. SPSS 21 was used for data analysis. The median (IQR) age of the patients was 51 (18) years in interventional group and 62 (11) years in control group. Male to female ratio was 18:9 in control group and 17:12 in Interventional group. Statistically significant results were detected within the groups regarding ejection fraction (EF), left ventricu...

Necrosis is an ancient topic which gains new attraction in the research area these years. There is no doubt that some necrosis can be regulated by genetic manipulation other than an accidental cell death resulting from physical or chemical stimuli. Recent advances in the molecular mechanism underlying the programmed necrosis show a fine regulation network which indicates new therapy targets in human diseases. Heart diseases seriously endanger our health and have high fatality rates in the patients. Cell death of cardiac myocytes is believed to be critical in the pathogenesis of heart diseases. Although necrosis is likely to play a more important role in cardiac cell death than apoptosis, apoptosis has been paid much attention in the past 30 years because it used to be considered as the only form of programmed cell death. However, recent findings of programmed necrosis and the related signalling pathways have broadened our horizon in the field of programmed cell death and promote new...

Spine stereotactic radiosurgery (SRS) offers excellent radiographic and pain control for patients with spine metastases. We created a prognostic index using recursive partitioning analysis (RPA) to allow better patient selection for spine SRS. Patients who underwent single-fraction spine SRS for spine metastases were included. Primary histologies were divided into favorable (breast/prostate), radioresistant (renal cell/sarcoma/melanoma) and other. Cox proportional hazards regression was done to identify factors associated with overall survival (OS). RPA was performed to identify factors to classify patients into distinct risk groups with respect to OS. A total of 444 patients were eligible. Median dose was 16 Gy (range 8-18) in 1 fraction and median follow-up was 11.7 months. At time of analysis, 103 (23.1%) patients were alive. Median OS was 12.9 months. RPA identified three distinct classes. Class 1 was defined as KPS > 70 with controlled systemic disease (n = 142); class 3 was...

Circular RNAs (circRNAs) are a newly discovered type of RNAs generated by back-splicing of precursor mRNA (pre-mRNA) and found in many species. They are, expressed in a tissue-specific manner and fulfill regulatory activities in many biological processes. Recent research revealed that circRNAs play critical roles in the development and pathologies of the cardiovascular system. Some of these circRNAs showed aberrant expression and regulatory activities during heart disease including heart failure and cardiac infarction and hypertrophy. These findings suggest that circRNAs might be a suitable target for the treatment and prevention of heart disease. In this review, we summarize the latest research on the biogenesis and functions of circRNAs with emphasis on the regulatory roles of circRNAs in the development and pathologies of the cardiovascular system. This article is protected by copyright. All rights reserved.

We tested the hypothesis that the early improvement in mood after the first hour of bright light treatment compared to control dim-red light would predict the outcome at six weeks of bright light treatment for depressed mood in patients with Seasonal Affective Disorder (SAD). We also analyzed the value of Body Mass Index (BMI) and atypical symptoms of depression at baseline in predicting treatment outcome. Seventy-eight adult participants were enrolled. The first treatment was controlled crossover, with randomized order, and included one hour of active bright light treatment and one hour of control dim-red light, with one-hour washout. Depression was measured on the Structured Interview Guide for the Hamilton Rating Scale for Depression-SAD version (SIGH-SAD). The predictive association of depression scores changes after the first session. BMI and atypical score balance with treatment outcomes at endpoint were assessed using multivariable linear and logistic regressions. No signific...

Immune dysfunction and a higher risk of uterine infections are characteristics of the transition into lactation in dairy cows. The supply of complexed trace minerals, which are more bioavailable, could help overcome the greater needs of these nutrients in tissues around parturition and early lactation. Twenty Holstein cows received an oral bolus with a mix of inorganic trace minerals (INO) or complexed trace minerals (AAC) to achieve 75, 65, 11, and 1 ppm supplemental Zn, Mn, Cu, and Co, respectively, in the total diet dry matter from -30 d through +30 d relative to parturition. Blood for polymorphonuclear leukocyte (PMNL) isolation was collected at -30, -15, +10, and + 30 d relative to parturition, whereas endometrium biopsies were performed at +14 and +30 d. Feeding AAC led to greater PMNL expression of genes related with inflammation response (DDX58), oxidative stress response (MPO), eicosanoid metabolism (PLA2G4A and ALOX5AP), transcription regulation (PPARG), and cellular adhes...

Micromonas is a unicellular marine green alga that thrives from tropical to polar ecosystems. We investigated the growth and cellular characteristics of acclimated mid-exponential phase Micromonas commoda RCC299 over multiple light levels and over the diel cycle (14:10 hour light:dark). We also exposed the light:dark acclimated M. commoda to experimental shifts from moderate to high light (HL), and to HL plus ultraviolet radiation (HL+UV), 4.5 hours into the light period. Cellular responses of this prasinophyte were quantified by flow cytometry and changes in gene expression by qPCR and RNA-seq. While proxies for chlorophyll a content and cell size exhibited similar diel variations in HL and controls, with progressive increases during day and decreases at night, both parameters sharply decreased after the HL+UV shift. Two distinct transcriptional responses were observed among chloroplast genes in the light shift experiments: i) expression of transcription and translation-related gen...

The purpose of this work was to evaluate measures of increased departmental workload in relation to the occurrence of physician-related errors and incidents reaching the patient in radiation oncology. All data were collected for the year 2013. Errors were defined as forms received by our departmental process improvement team; of these forms, only those relating to physicians were included in the study. Incidents were defined as serious errors reaching the patient requiring appropriate action; these were reported through a separate system. Workload measures included patient volumes and physician schedules and were obtained through departmental records for daily and monthly data. Errors and incidents were analyzed for relation with measures of workload using logistic regression modeling. Ten incidents occurred in the year. The number of patients treated per day was a significant factor relating to incidents (P < 0.003). However, the fraction of department physicians off-duty and th...

A disintegrin and metalloproteinase 33 (ADAM33) gene has been considered as an asthma susceptibility gene due to its possible role in airway remodeling, abnormal cell proliferation and differentiation. Association of this gene with asthma has been reported in several genetic studies on various populations. The current study aims to evaluate the association of ADAM33 gene polymorphisms with the risk of asthma in the Punjabi population of Pakistan. A total of 101 asthma patients and 102 age-matched healthy controls from Lahore, a city in Punjab, were recruited. ADAM33 single nucleotide polymorphisms (SNPs) T+1(rs2280089), T2(rs2280090), T1(rs2280091), ST+5(rs597980), ST+4(rs44707), S2(rs528557), Q-1(rs612709) and F+1(rs511898) were genotyped in both patients and controls using single base extension and capillary electrophoresis-based genetic analyzer. The basic allelic and genotypic model was analyzed for association of the SNPs with asthma using SHEsis software. Haploview software was used to calculate pairwise linkage disequilibrium (LD) among six of the genotyped SNPs. Of the 8 SNPs genotyped, only S2(rs528557) showed significant association with asthma (Allele p value=0.0189, Genotype p value= 0.021). SNPs T+1(rs2280089), T2(rs2280090), T1(rs2280091), ST+4(rs44707), S2(rs528557) and Q-1(rs612709) were found to be in moderate to strong LD. The significantly higher frequency of haplotype "AAGTCG" in healthy controls suggests a protective effect against asthma risk in the studied population (p value=0.0059). These findings suggest that genetic variants of ADAM33 gene may play important roles in asthma susceptibility in the Punjabi population of Pakistan.

Drosophila melanogaster larvae are classified as herbivores and known to feed on non-carnivorous diet under normal conditions. However, when nutritionally challenged these larvae exhibit cannibalistic behaviour by consuming a diet composed of larger conspecifics. Herein, we report that cannibalism in Drosophila larvae is confined not only to scavenging on conspecifics that are larger in size, but also on their eggs. Moreover, such cannibalistic larvae develop as normally as those grown on standard cornmeal medium. When stressed, Drosophila melanogaster larvae can also consume a carnivorous diet derived from carcasses of organisms belonging to diverse taxonomic groups, including Musca domestica, Apis mellifera, and Lycosidae sp. While adults are ill-equipped to devour conspecific carcasses, they selectively oviposit on them and also consume damaged cadavers of conspecifics. Thus, our results suggest that nutritionally stressed Drosophila show distinct as well as unusual feeding behav...

Abstract. In the present work we report some results based on the study of mean multiplicities, multiplicity distributions of various charged secondaries and some of their correlations along with angular distributions of the target fragments produced in the ...

Email: The effect of triflumuron and diafenthuron (LC , LC , LC) on total and differential 40 50 60 rd th haemocyte was evaluated on 3 and 5 instar larvae of Helicoverpa armigera. The total rd haemocyte count just after the application of LC of triflumuron in 3 instar larvae increased 50 3 3 (78900cells/mm), while decreased (83800 cells/mm) after half an hour, and increased again 3 3 (90200 cells/mm) after one hour of application from the normal count (68175 cells/mm). The percentage of prohaemocytes decreased from normal (42% to 26%), whereas the percentage of plasmatocytes, spherulocytes, cystocytes, and granulocytes increased from normal (18%, 29%, 2.75% and 8.25% to 29%, 32%, 4% and 10% respectively after the th application of insecticide. Similar results were recorded with 5 instar larvae. The total rd haemocyte count just after the application of LC of diafenthuron in 3 instar larvae 50 3 3 increased (82400 cells/mm) from the normal count, while decreased (79900 cells/mm) 3 af...

Background/Question/Methods Climate change has the potential to disrupt trophic interactions between plants, primary and secondary consumers, which may lead to a change in the structure of terrestrial communities. The present study examines the effects of drought on an above/below-ground system involving a Brassica plant, a generalist and a specialist aphid species (foliar herbivores), their parasitoids, and a dipteran species (root herbivore). While a number of studies have examined the effects of above/below-ground interactions in multitrophic systems, there have been very few studies on the effects of abiotic factors on systems involving both above- and below-ground interactions. Experiments were conducted under controlled environment conditions. In the drought treatment, the quantity of water added per plant per week was 50 % of the full (control) water regime. We examined the effect of drought, with and without root herbivory, on the olfactory response of parasitoids (preferenc...

Correlations between particles produced in the interactions of 28 Si and 12 C nuclei with emulsion nuclei at 4.5A GeV/c has been investigated. 701 events of 28 Si and 844 of 12 C interactions have been analysed. A method which combines techniques from the method of using the two-particle correlation functions and from rapidity-gap distributions is applied. This method has been used successfully by others to study the correlation in P-Em and light-ion interactions. However, we have applied it to the heavy-ion collision data. Small but significant departure from zero-correlation is observed.

This article reviews the most prevalent sensory illness of mammals especially humans – Genetic Deafness or hearing loss (HL). For genetic hearing loss more than 100 candidate genes have been discovered. The most common candidate gene of these all that is found all around the world is GJB2 gene. Different types of mutations are found in GJB2 gene. Some of these mutations are non-sense while some are sense mutations. This study is focus on mutation in GJB2 gene and its prevalence in different region of the world.

The involvement of smart grid in home and building automation systems has led to the development of diverse standards for interoperable products to control appliances, lighting, energy management and security. Smart grid enables a user to control the energy usage according to the price and demand. These standards have been developed in parallel by different organizations, which are either open or proprietary. It is necessary to arrange these standards in such a way that it is easier for potential readers to easily understand and select a suitable standard according to their functionalities without going into the depth of each standard. In this paper, we review the main smart grid standards proposed by different organizations for home and building automation in terms of different function fields. In addition, we evaluate the scope of interoperability, benefits and drawbacks of the standard.

ABSTRACT Cancer recurrence and metastatic tumors might arise not only from residual primary tumor cells but even from precancerous cells that are able to spread and seed distant organs. Thus, residual pre-neoplastic and neoplastic cells that persist following treatment constitute an ideal evolutionary niche for cancer evolution. We have investigated the role of the TGF-beta; signaling pathway, which is widely known as a pro-metastatic in late stages of tumor progression, in the context of the cellular response to genotoxic stress induced by chemotherapy drugs. We identified that TGF-beta signaling contribute to drug resistance by repressing the DNA damage response through a coordinate repression of transcription and translation of p53 and the stress response in precancerous and cancer cells. Indeed, TGF-beta/Smad signaling enacts an intrinsic survival pathway in metastatic cancer cells. However, the molecular events accompanying the evolution towards a drug tolerant phenotype are not well understood. Indeed, severe cellular stress might generate or select a subpopulation of reversibly stress-tolerant cells under conditions that are lethal to the majority of the population. Thus, drug tolerance could be attributed to heterogeneity of gene expression within the population to ensure survival of a minority under stress. To address these questions, we developed an experimental paradigm to generate and propagate populations of paclitaxel tolerant precancerous (MCF10A) and metastatic cancer (MDA-MB-231) cells that can resume proliferation after 1 week of consecutive treatment with lethal doses of the drug. We found that drug-tolerant cells reacquired Paclitaxel-sensitivity after expansion. Then we performed whole transcriptome sequencing to identify single nucleotide variants (SNVs) and gene expression profiles at the single-cell level associated with the evolution towards a reversible drug tolerant state in cancer cells. We evaluated untreated, stress-arrested and proliferating drug-tolerant cells from a small (n<64) clonal population. In addition to sequencing the mRNA of single cells, we also performed DNA and RNA sequencing of populations of untreated and drug-tolerant cells to aid in the identification of RNA variants. We performed differential gene expression profiling for single cells and population cells of the three groups to identify the transcriptional stress response and cytotoxic effects of Paclitaxel on gene expression. We find that within untreated, stress-arrested and drug-tolerant cell groups, specific transcriptional programs were enacted while generating high heterogeneity between single cells within and between groups. Drug-tolerant cells contained specific RNA variants encoded by genes involved in microtubule organization and stabilization as well as cell adhesion and cell surface signaling. Unexpectedly, Drug-tolerant cells from a single progenitor cell rapidly reacquired high degree of heterogeneity in gene expression similar to untreated cells, within a few doublings, while uniquely expressing SNVs and genes such as Integrin alpha 6, the histone demethylase KDM5A, and the IGF-1 receptor. Interestingly, despite of the high degree of heterogeneity, the whole gene expression profiles, of each cell rather than small gene sets can identify the response of cells to taxol. Thus, single cell analyses reveal the dynamics of the response to stress in terms of cell-specific SNVs driving heterogeneity, the survival of a minority population through generation of specific genes and RNA variants and the efficient reconversion of drug-tolerant cells back to normalcy, suggesting that such heterogeneity within cancer cell populations might provide evolutionary advantage to increase the pool of drug tolerant cells poising a prospective path towards drug resistance. Citation Format: Fernando Lopez-Diaz, Mei-Chong Wendy Lee, Muhammad Tariq, Shahid Khan, Yelena Dayn, Charlie Vaske, Nader Pourmand, Beverly M. Emerson. Single-cell RNA sequencing reveals phenotypic plasticity of drug tolerant, clonal populations of cancer cells. [abstract]. In: Proceedings of the AACR Precision Medicine Series: Drug Sensitivity and Resistance: Improving Cancer Therapy; Jun 18-21, 2014; Orlando, FL. Philadelphia (PA): AACR; Clin Cancer Res 2015;21(4 Suppl): Abstract nr A09.

The present study was based on the general hypothesis that boron may affect the accumulation and utilization of other micronutrients in plants. A field experiment was conducted to find the effect of boron on yield, quality and micronutrients content of flue cured virginia tobacco (Nicotiana tabacum L.) at Tobacco Research Station Khan Garhi, Mardan-Pakistan, during 2010-11. Two varieties TM-2008 and Speight G-28 were tested and six levels of boron (0, 0.5, 1, 2.0, 3.0 and 5.0 kg ha-1 ) in the form of boric acid, in RCB design in split plot arrangement and replicated thrice. A basal dose of 70 kg ha- 1 each N, P2O5 and K2O were applied. Recommended levels of micronutrients (Zn, Cu, Fe and Mn) were applied in sulphate form. Results indicated that the yield of tobacco crop significantly increased at 1 kg B ha-1 and then decreased linearly in both varieties. In variety Speight G-28 a maximum leaf area, green leaf weight, cured leaf weight and grade index were recorded as 800.9 cm2 , 156...

Hepatitis C virus (HCV) infection is a worldwide health problem affecting about 300 million individuals. HCV causes chronic liver disease, liver cirrhosis, hepatocellular carcinoma, and death. Many side effects are associated with the current treatment options. Natural products that can be used as anti-HCV drugs are thus of considerable potential significance. NS3 serine protease (NS3-SP) is a target for the screening of antiviral activity against HCV. The present work explores plants with anti-HCV potential, isolating possible lead compounds. Ten plants, used for medicinal purposes against different infections in rural areas of Pakistan, were collected. The cellular toxicity effects of methanolic extracts of the plants on the viability of Huh-7 cells were studied through the Trypan blue dye exclusion method. Following this, the anti-HCV potential of phytoextracts was assessed by infecting liver cells with HCV-3a-infected serum inoculum. Only the methanolic extract of Portulaca oleracea L. (PO) exhibited more than 70% inhibition. Four fractions were obtained through bioassay-guided extraction of PO. Subsequent inhibition of all organic extract fractions against NS3 serine protease was checked to track the specific target in the virus. The results showed that the PO methanolic crude and ethyl acetate extract specifically abridged the HCV NS3 protease expression in a dose-dependent fashion. Hence, PO extract and its constituents either alone or with interferon could offer a future option to treat chronic HCV.

To evaluate the clinical characteristics and predictors of in-hospital mortality in patients with infective endocarditis at a tertiary care centre in Pakistan. The cross-sectional study was conducted at the Aga Khan University Hospital, Karachi, from January 1, 2002, to December 31, 2006, and comprised 84 consecutive patients hospitalised with infective endocarditis,. All patients underwent verification of the diagnosis according to the Modified Duke criterion. Data was collected through a questionnaire and analysed using Student's t test, Chi square and Fisher's exact test. Univariate and multivariate logistic regression analysis was performed to assess predictors of mortality. Of the total, 53(63%) patients were male and 31(37%) female. The mean age of the patients was 42+17 years. Overall, 34(41%) patients had rheumatic valve disease as a predisposing condition. The most commonly affected valve was mitral in 43(51%) patients, and the most commonly isolated organism was me...