پروفیسر حامد حسن قادری
افسوس ہے کہ ادھر چند مہینوں کے اندر دنیائے علم و ادب کی کئی نامور ہستیوں، پروفیسر حامد حسن صاحب قادری، سید ہاشمی صاحب فرید آبادی اور مولانا صلاح الدین احمد نے انتقال کیا، پروفیسر حامد حسن صاحب قادری ہماری پرانی علمی بزم کی یادگار تھے، اردو اور فارسی زبان و ادب اور اس کی تاریخ پر ان کی نظر بڑی گہری اور وسیع تھی، تاریخ داستان اردو ان کی وسعت نظر کی شاہد ہے، وہ عرصہ تک سینٹ جانس کالج آگرہ میں اردو اور فارسی کے استاد رہے، ریٹائر ہونے کے بعد کراچی چلے گئے تھے، اور وہیں وفات پائی، ان کی وفات سے ایک پرانی علمی و تہذیبی یادگار مٹ گئی۔
(شاہ معین الدین ندوی، اگست ۱۹۶۴ء)
In Pakistan, the financial issues of married working women are rarely discussed. There is an absence of literature on the subject. Nevertheless, the social sciences literature has been debating financial aspect of gender, either from the perspective of employer or employee; ignoring the working women’s reservations regarding their financial contribution in their marital life, particularly with reference to spouse and in-laws expectations. This issue becomes more acute when it comes to patriarchal conservative developing societies. This study is a delicate attempt to understand the magnitude of financial support of Pakistani married working women for spouse and in-laws, in the city of Lahore. In routine, the husband as well as the in-laws expect that a working wife should surrender her income, in entirety or partially towards the household budget, thus taking the financial responsibility of her spouse along with his extended family. Such financial misgivings create tensions and pressure for the already burdened woman having a disadvantaged status. In certain cases, the contribution is by free will of the wife, as well. This research will make an attempt through a survey with 50 married working women of different social classes, residing in Lahore. The purpose is to understand the rationale of approval or disapproval of this practice. Refusal for cooperation often create problems for the earning woman, even at the risk of separation or divorce, or at the least, tensions in the married life. At the end, the study will debate over possible adjustments and compromises, which could reduce tense situation for the married working woman, and at the same time maintaining her financial independence.
In this thesis, the medical condition of sepsis is considered at molecular level (signalling pathways) using computational systems-level approaches in order to get insights into the mechanism of disease progression. Sepsis is the pathological condition provoked due to the presence of bacterial endotoxin in the bloodstream. Subsequently Toll like receptors (TLR)4 and JAK/STAT signalling pathways attempt to reduce the pathogen burden by inducing pro- and anti-inflammatory innate immune responses. However, in some instances, an overwhelmed immune system could not properly regulate the balance between infection and inflammation that may ultimately lead to organ damage and consequently to death. In recent years, there has been an increasing amount of literature on the pattern of pro- and anti-inflammatory response elicited during sepsis, though; there has been a little agreement on the roles of pro- and antiinflammatory cytokines (AiCyts) in sepsis. This study mainly aims to address the controversy behind roles of pro- and anti-inflammatory cytokines in sepsis by modelling the signalling pathway of TLR4 and one of the connected signalling cascades of JAK/STAT using qualitative modelling approach introduced by René Thomas’. The possible system dynamics of TLR4-JAK/STAT signalling pathways are produced for two medical conditions i.e. non-sepsis (type of infections that generally do not cause sepsis) and sepsis along with perturbations in these two cases. As a result, recurrent induction and inactivation of pro-inflammatory cytokines is found as the basic feature associated with sepsis. Besides AiCyts, IFN-β and SOCS-1 are found to mediate down-regulation of pro-inflammatory cytokines at different stages of signalling which cause variation of pro-inflammatory cytokines levels. It is observed that intervention in IFN-β mediated down-regulation of pro-inflammatory cytokines at earlier stages of system dynamics, while intervening the SOCS-1 mediated down-regulation of proinflammatory cytokines at later stages ensures hyper-inflammatory condition. On the other hand, interventions in TLR4, NFκB (transcription factor involved in the TLR4 1 Abstract signalling pathway) and JAK/STAT signalling are good choices for supporting the anti-inflammatory immune responses. Thus only possible protein-protein interactions involved in the initial downstream interactions of TLR4 signalling are studied in order to predict a more appropriate target in these interactions. Previous studies indicated that MyD88 adaptor-like protein (MAL) is an endogenous adaptor protein recognized as an important protein involved in the induction of TLR4 mediated downstream signalling pathway. Moreover, it has also been demonstrated that BTK and PKCδ phosphorylate MAL (positions Tyr86 and Tyr106) which ultimately activates MAL. Thus the modelling of PKCδ and protein-protein interactions of both BTK and PKCδ with MAL is performed in order to explore their competitive interaction. Molecular docking and physicochemical analysis reveals that PKCδ may phosphorylate only Tyr106 of MAL, while BTK may phosphorylate MAL at both positions. Interestingly, the charge and hydrophobicity at interfaces of PKCδ and BTK are found different in nature yet well-compatible with the individual positions of Tyr86 and Tyr106 of MAL. The most prominent findings emerged from this analysis is that position Tyr86 of MAL may explicitly be phosphorylated by BTK, while position Tyr106 of MAL may be phosphorylated by the competing interest of both PKCδ and BTK. In conclusion, this thesis will enhance our understanding about the signalling and protein-protein interactions involved in sepsis which will contribute to the development of drugs and vaccines against the medical condition of sepsis.