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Small interfering RNAs (siRNAs) are a new class of drugs, exhibiting sequence-driven, potent, and sustained silencing of gene expressionin vivo. We recently demonstrated that siRNA chemical architectures can be optimized to provide efficient delivery to the CNS. Many genetically-defined neurodegenerative disorders are autosomal dominant favoring selective silencing of the mutant allele. In some cases, successful targeting of the mutant allele requires targeting of a single nucleotide polymorphism (SNP) heterozygosity. Using Huntington’s disease as a model, we demonstrate allele-specific RNAi-based silencing of gene expressionin vivoand in neurons differentiated from HD patient-derived iPSCs. A series ofin vitroscreens, with chemical and thermodynamic optimization, identified compounds with >50-fold selectivity for the mutant HD-causing allele, based on a single nucleotide difference. The optimized compound exhibits selective silencing of mutant huntingtin (HTT) protein in patient derived cells and throughout the HD mouse brain, providing a demonstration of SNP-based allele-specific RNAi silencing of gene expressionin vivoin the CNS. The ability to target a disease-causing allele using RNAi-based therapies could be applied to a wide range of dominant CNS disorders, where maintenance of wild-type expression is essential.

With the increased competitiveness and significance of the workforce, the responsibility of organizational leaders has been increased to behave ethically and lead their followers in the best ethical way. This study aims to explore how the perception and trust of followers of their middle-level managers can shape the ethical behavior of middle managers and their bottom-line mentality. This qualitative study was conducted using semi-structured interviews from 10 employees of two Pakistani textile organizations-selecting five employees from each. Thematic analysis was used for data analysis. The findings reported that the bottom-line mentality demands are given priority. Thus, to achieve these demands, ethical values are being ignored while the nature of the task and attitude of the supervisor leads towards the social undermining of the employees. Furthermore, it has been found that leaders' behavior and personality are more important in building trust and perception of employees, and this perception does not entail that leader will be acting ethically in real, but they are perceived to be. This study can provide valuable implications for policymakers, especially HR personnel, to device policies by considering ethical leadership practices. The findings of this research recommend that better performance and profit maximization by employees can be enhanced by reducing the bottom-line mentality of top management. Few scholars have elaborated on ethical leadership, the complexity of the leader-follower relationship, and individual perceptions. Behavioral aspects, bottom-line mentality, and trust from employees' perspective in ethical leadership have received little attention. In addition, this research has taken a step forward by exploring the collectivist country of Pakistan.

We report on three Zn(II) coordination frameworks based on benzobisimidazole which were prepared utilizing organic ligands containing methyl groups in the 2-position of the imidazole rings. The molecular structure of the prepared coordination frameworks was revealed by single crystal X-ray structure analysis. The influence of the methyl group on the crystal packing motifs of the materials was investigated and compared to structurally related compounds (which were prepared under the same or very similar reaction conditions) containing no methyl groups in the 2-position of the imidazole rings. Additionally, the thermal stability of the prepared coordination frameworks investigated by variable temperature XRPD and thermogravimetric analysis, and their photoluminescence properties are reported.

The old female population of Pakistan is suffering more from diabetes as this is may be due to eating habits and obesity. The main objective of the study is to find the relationship of obesity, and diabetes in old female population of Pakistan. This cross sectional study was conducted in CIMS, Bahawalpur during January 2019 to October 2019. This study was based on local female population of Lahore, age range from 30 to 50 who was suffering from diabetes and they are also obese. This study was done with the permission of hospital ethical committee and with the written consent of patients. First of all we collect the demographic data of all females, it includes living habits, eating habits, social and economic back ground. The mean age (±SD) was 40 ± 10 years. Mean duration of diabetes was 5 years, mean HbA1c was 8.1% and 53.7% were on oral agents and rest was on insulin with or without oral agents. Hypertension was present in 65.7%, 13.7% had known coronary artery disease and 2.3% had a cerebrovascular accident previously. According to the analysis of data there is a positive correlation between obesity and diabetes in the environment like Pakistan. Because female suffer from hypertension, weight gain and due to this from diabetes.

The main objective of the study is to find the role of antioxidants in diabetic HCV patients in Pakistan. This cross sectional study was conducted in CIMS, Bahawalpur during January 2019 to October 2019. This study was conducted according to the rules and regulations of authority. For this research purpose we selected 50 individuals of both genders. This study was carried out on 50 patients who were categorized into three groups i.e., control, HCV patients and HCV/diabetes patients. The blood was collected from a cuboital vein of patients and serum was separated within one hour ny centrifugation. Our results shows that antioxidants are the important biomarkers for the diagnosis of liver problems in diabetic patients. The level of SOD, CAT, GSH and MDA were decreases in diabetic HCV patients as compared to normal and simple HCV patients. The important biomarker is MDA and SOD. It is concluded that antioxidants levels have been related to various disease processes and play a significant role in the pathogenesis of diabetic complications. Their plasma levels are usually used as a marker of lipid peroxidation. Plasma MDA, SOD, GSH and CAT was elevated in chronic hepatitis C and liver cirrhosis patients.

Zora Neale Hurston's (1891-1960) is an outstanding African American novelist, playwright, autobiographer and essayists. Her work is considered as an important part of the African American and Harlem Literature.**** It represents a milestone and a keystone in the African-American literary canon because it breaks from the style of the previous works and makes a beginning of a new style. Hurston shifts from the black works that stick to racial themes and sheds the light on new aspects and themes in blacks' life especially on feminist themes. Her exceptional fame culminates in her novel Their Eyes Were Watching God (1937). 1 Their Eyes Were Watching God examines with a great deal of artistry the struggle of a black woman named Janie Crawford to escape the fetters of the traditional concept about love and marriage and the narrow social restrictions of her class and sex. She neglects others' judgment on her and is brave enough to strive for her dream.2 The paper concentrates on this novel to show the concept of love and marriage through the story of Janie's Crawford, the novel's protagonist. In Janie's plight towards liberty and recognition, love and happiness, Hurston reflects the colored women's thrives and experiences in the American black society. Janie, who has the concept that marriage must involve love and happiness, goes for a search of unconditional and fulfilling love which she finally finds with her third husband Tea Cake, but only after she has passed through the wasteland of being a possession before entering the pear tree garden of her actualized dreams of love and happiness.

The effects of ajmaline on human platelet aggregation, arachidonate metabolism and platelet activating factor (PAF)-induced lethality in rabbits were examined. Platelet aggregation induced by several stimuli (ADP, collagen, and PAF) was inhibited by increasing concentrations of ajmaline. The potency of ajmaline was higher when PAF was employed as stimulating agent in comparison with other agonists (IC50 70, 270 and 380 μm for PAF, ADP and collagen, respectively) whereas ajmaline had no effect against arachidonic acid-induced aggregation. In contrast however, ajmaline inhibited arachidonate metabolism by platelet homogenates. The formation of both thromboxane A2 and 12-hydroxy-eicosatetraenoic acid was inhibited by ajmaline with comparable potencies. Pretreatment of rabbits with ajmaline (50 mg kg−1) completely abolished the lethal effects of PAF (11 μg kg−1) given intravenously (P < 0·001). In addition, ajmaline at doses ranging from 50 to 100 mg kg−1 inhibited carrageenan-induced rat paw oedema (P < 0·001). In this test ajmaline was three times more potent than aspirin. In the light of these results we conclude that ajmaline, a known anti-arrhythmic agent is a PAF antagonist and a dual inhibitor of platelet cyclo-oxygenase and lipoxygenase enzymes with anti-inflammatory properties.

In open multiagent systems, individual components act in an autonomous and uncertain manner, thus making it difficult for the participating agents to interact with one another in a reliable environment. Trust models have been devised that can create level of certainty for the interacting agents. However, trust requires reputation information that basically incorporates an agent’s former behaviour. There are two aspects of a reputation model i.e. reputation creation and its distribution. Dissemination of this reputation information in highly dynamic environment is an issue and needs attention for a better approach. We have proposed a swarm intelligence based mechanism whose self-organizing behaviour not only provides an efficient way of reputation distribution but also involves various sources of information to compute the reputation value of the participating agents. We have evaluated our system with the help of a simulation showing utility gain of agents utilizing swarm based reputation system. We have utilized an ant net simulator to compute results for the reputation model. The ant simulator is written in c

In this paper we have analyzed and developed a formal specification of a Trust Model in Semantic Grid Registry. This paper formalizes the basic requirements of a trust model in case of semantic grid registry. We have described the flow of operations of our system through links and processes in the system architecture. The system is formally modeled in Pi-Calculus. Finally we transformed the specification to Pi- ADL and generated code using Archware tool. We have already developed a Semantic Grid Registry.

In Open Multiagent systems, individual components act in an autonomous and uncertain manner, thus making it difficult for the participating agents to interact with one another in a reliable environment. Trust models have been devised that can create level of certainty for the interacting agents. However trust requires reputation information that basically incorporates an agent's former behavior. Dissemination of this reputation information in highly dynamic environment is an issue. We have proposed a swarm intelligence based mechanism; whose self-organizing behavior provides an efficient way of reputation distribution.

Organizations and individuals have been facing disasters globally and locally since hundreds of years. Increasing number of natural disasters has demonstrated the paramount importance of the natural hazards subject for the protection of environment and the citizens. Now more than ever, designing an efficient traffic system, moving vast amounts of helping goods quickly and safely across great distances is one of our most pressing needs. Satellite navigation systems are changing the way in which we travel from place to place whether by land, sea or air and whether in remote areas or through congested city streets. Global positioning system (GPS) and its role in advanced transportation projects is inseparable and become a synonym. The management and operations of vehicles and giving real-time information to users that will lead to cost-effective and satisfied service to passengers is possible nowadays using a GPS based vehicle navigation system and communication via remote sensing. This paper describes how the already developed fleet management and remote sensing technologies can be merged together to form an efficient disaster management system.