Rethinking connectivity as interactivity: a case study of Pakistan

Connectivity in developing countries has traditionally been viewed in terms of investment in transport and communications. This papers makes an effort to go beyond this traditional view and conceptualizes connectivity as networks between people and places. We split the overall national reforms agenda for connectivity into three prongs: a) transportation and related services, b) ICT, and c) social capital. We try to see the state of each of these three in case of Pakistan and then propose reforms keeping in view the current political economy milieu.Connectivity; Economic Growth; Transport; Communications; Social Capital

A Possible Explanation of the Missing Deflation Puzzle

Following the Great Recession, despite large and persistent slowdown in economic activity, the fall in inflation was modest. This is known as the missing deflation puzzle. In this paper, we develop and estimate a New Keynesian model to provide an explanation for the puzzle. The new model allows for time-varying volatility in cross-sectional idiosyncratic uncertainty and accounts for changes in intermediate input prices. We show that inflation did not fall much because intermediate input prices were increasing

Virulence factors in Streptococcus pyogenes

Während meiner Dissertation lag mein Interesse in der Erweiterung des Verständnisses der Pathogenität des bekannten humanen Pathogens Streptococcus pyogenes, auch bekannt als Gruppe A Streptococcus (GAS). Dieses Manuskript ist in vier Teile unterteilt: 1) die Rolle von Superantigen-codierenden lysogenen Bakteriophagen in Erwerb und Verbreitung von Virulenzgenen in Streptococci, 2) der Identifikation von small RNAs mit potentiellen regulatorischen Funktionen in GAS, 3) der Rolle des interspezifischen Kommunikationssystems luxS/AI-2 in GAS Metabolismus und Überleben unter Stresskonditionen und 4) der Rolle von Streptolysinen in der angeborenen Immunantwort von Makrophagen auf GAS Infektion. 1) Seit den späten 1980er Jahren, war ein signifikanter Anstieg von schweren Formen durch GAS verursachter Krankheiten im Menschen zu beobachten. Eine Hypothese um dieses Phänomen zu erklären, beruht auf einer gesteigerten Virulenz des Pathogens selbst. In GAS codieren Prophagen für einen oder mehr putative oder bekannte Virulenzfaktoren, einschließlich Superantigenen. Im ersten Teil meiner Dissertation wird die Identifikation des induzierbaren Prophagen F149, welcher für das Superantigen SSA in einem klinischen Isolat von GAS des Serotyps M12 codiert, beschrieben. Durch lysogene Konversion war der Phage zwischen klinischen Isolaten von verschiedenen GAS M-Serotypen (M1, M3, M5, M12, M19, M28 und M94), als auch in Gruppe C Streptococcus equisimilis (GCSE), ex-vivo transferierbar. Unsere Ergebnisse zeigen, dass horizontaler Transfer von lysogenen Phagen zwischen GAS durch die M-Typ-Barriere möglich ist und unterstützen das Konzept der interspezifischen lysogenen Toxin-Konversion. Somit würde lysogene Konversion es GAS ermöglichen, sich effizienter an die wechselnden Bedingungen im Wirt anzupassen, was wiederum zu potentiell konkurrenzfähigeren, virulenteren Klonen führen würde. 2) Kürzlich erschienene Studien zeigen, dass small RNAs (sRNAs) in Bakterien eine signifikante Rolle in der Regulation der Genexpression spielen. Jedoch sind Informationen über die Rolle von sRNAs in S. pyogenes relativ begrenzt. Aus diesem Grund war unser Ziel im zweiten Abschnitt meiner Arbeit die Identifikation neuer sRNAs in S. pyogenes. Zu diesem Zweck wurde ein in silico Verfahren angewandt, fokussierend auf die intergenen Regionen des Genoms von M1-Serotyp GAS. Von 178 identifizierten putativen Loci wurden 90 zur weiteren Analyse ausgewählt, wobei 29 (32%) dieser sRNAs unter normalen Wachstumsbedingungen exprimiert werden. Die Expression der Kandidaten wurde verifiziert in den Serotypen M1, M3, M5 und M49, ihre 5’ und 3’ Enden wurden determiniert, ihre Stabilität bestimmt und ihre in silico Sekundärstruktur wurde vorhergesagt. Gefunden wurden 5 Riboswitches, 6 leader elements, 4 funktionelle RNAs, 8 T-Boxen und 5 neue sRNAs. Zwei dieser sRNA Kandidaten befinden sich in der 5’ UTR von Riboflavin- und Tryptophan- Transportergenen und scheinen diese Gene durch trankriptionelle oder translationelle Attenuierungsmechansimen zu kontrollieren. Das zeigt die Wichtigkeit von sRNAs in der Kontrolle der Aufnahme essentieller Metaboliten in Bakterien durch regulatorische Genexpression. Zusätzlich wurde eine in der intergenen Region identifizierte sRNA SpyRNA049 auf ihre potentielle Rolle in GAS-Pathogenität weiter analysiert. 3) Frühere Studien zeigten, dass das interspezifische Zell-Zell-Kommunikationssystem luxS/AI-2 eine Rolle in Metabolismus und Pathogenität spielt. Im dritten Abschnitt meiner Dissertation war das Ziel, die Rolle des luxS/AI-2 Systems in den S. pyogenes Serotypen M1 und M19 zu verstehen. Unsere Ergebnisse lassen auf eine limitierte Rolle von luxS/AI-2 im S-Adenosylmethioninzyklus schließen. Überlebensassays mit luxS-Mutanten sowie luxS-Expression und AI-2-ähnliche Aktivitätsassays im leicht sauren Milieu demonstrierten die Beteiligung des luxS/AI-2 Systems in der Stressadaptation von GAS. Interaktionsanalyse mit Wirtszellen zeigte, dass die luxS-Mutanten im Vergleich zum Wildtyp in höherem Ausmaß in Epithelzellen und Makrophagen überlebten. Alles in allem zeigen unsere Daten, dass das luxS/AI-2 System nicht nur in die Regulation der Virulenzfaktorexpression involviert ist, sondern auch für Bakterien einen Vorteil darstellt, in herausfordernden Wirtsumgebungen zu überleben. 4) Im Allgemeinen werden Bakterien von den Immunzellen des Wirts durch pattern recognition receptors, wie Toll-like receptors (TLRs), erkannt. Über die Erkennung von GAS durch Makrophagen ist jedoch wenig bekannt. Die Ergebnisse, die im vierten Teil meiner Dissertation beschrieben werden, lassen darauf schließen, dass Makrophagen S. pyogenes unabhängig von den TLRs die typisch für gram-positive Pathogene sind (TLR2, TLR4 und TLR9 sowie ihre Kombinationen), erkennen. Jedoch waren die in Makrophagen beobachteten Signalereignisse auf GAS-Infektion immer noch abhängig vom TLR-Adaptor MyD88. Überraschenderweise war die IFN-Produktion unabhängig von den GAS-Cytolysinen SLS und SLO, die oft von anderen gram-positiven Bakterien benötigt werden. Alles in allem lassen unsere Ergebnisse darauf schließen, dass GAS durch einen MyD88-abhängigen Rezeptor, anders als die üblicherweise verwendeten, erkannt wird und lassen einen neuen Typ der bakteriellen Erkennung für die Produktion von TypI IFN erkennen.During my thesis work, I have been interested in extending our understanding of the pathogenicity of the notorious human pathogen Streptococcus pyogenes, also called group A streptococcus (GAS). This thesis manuscript is divided into four parts: 1) role of superantigen-encoding lysogenic bacteriophages in the acquisition and spread of virulence genes among streptococci, 2) the identification of small RNAs with potential regulatory functions in GAS, 3) the role of the interspecies communication system luxS/AI-2 in GAS metabolism and survival under stress conditions and 4) the role of streptolysins in the innate immune responses of macrophages upon GAS infection. 1) Since the late 1980s, there has been a significant reemergence of severe forms of human diseases caused by GAS. One hypothesis to explain this phenomenon has focused on an enhanced virulence of the pathogen itself. In GAS, prophages encode one or more putative or established virulence factors including superantigens. The first part of my thesis describes the identification of an inducible prophage F149 encoding superantigen SSA in an M12 GAS clinical isolate. By lysogenic conversion the phage was transferable ex-vivo among GAS clinical isolates of various M serotypes (M1, M3, M5, M12, M19, M28 and M94) as well as of Group C Streptococcus equisimilis (GCSE). Our data indicate that horizontal transfer of lysogenic phage among GAS can occur across the M-type barrier and provide further support for the concept of interspecies lysogenic toxin-conversion. Therefore, lysogenic conversion would allow GAS to more efficiently adapt to the changing host conditions, thus potentially leading to fitter and more virulent clones. 2) Recent studies show that in bacteria small RNAs (sRNAs) play a significant role in the regulation of gene expression. However, information regarding sRNAs in S. pyogenes is rather limited. Thus, in the second part of my thesis, our aim was to identify novel sRNAs in S. pyogenes. For this purpose, we used an in silico approach focusing on the intergenic regions of the GAS M1 serotype genome. From 178 identified putative loci, 90 were further selected for analysis and 29 (32%) of these sRNAs showed expression under normal growth conditions. Expression of the candidates was verified in M1, M3, M5 and M49 serotypes, their 5’ and 3’ ends were mapped, their stability was determined and their in silico secondary structures were predicted. We found 5 riboswitches, 6 leader elements, 4 functional RNAs, 8 T-boxes and 5 novel sRNAs. Two of the sRNA candidates residing in the 5’ UTR of the riboflavin and tryptophan transporter genes seemed to control the transporter genes via transcriptional or translational attenuation mechanisms. This shows the importance of sRNAs in the control of the uptake of essential metabolites by regulating gene expression in bacteria. In addition, one sRNA SpyRNA049 identified in the intergenic region, was further analyzed for its potential role in GAS pathogenicity. 3) Previous studies showed that the interspecies luxS/AI-2 cell-cell communication system plays a role in metabolism and pathogenicity. In the third part of my thesis we aimed at understanding the role of the luxS/AI-2 system in S. pyogenes serotypes M1 and M19. Our results indicated a limited role of luxS/AI-2 in the activated methyl cycle metabolism. Survival assays with luxS mutants as well as luxS expression and AI-2 like activity assays under low acidic conditions demonstrated the involvement of luxS/AI-2 system in the adaptation of GAS to stress. Interaction analysis with host cells showed that the luxS mutants survived in epithelial cells and macrophages to a higher degree compared to the wild-type. Overall, our data show that the luxS/AI-2 system is not only involved in the regulation of virulence factor expression but also provides bacteria an advantage to survive in challenging host environments. 4) Bacteria are generally recognized by host immune cells by the pattern recognition receptors like toll-like receptors (TLRs). However, little is known about the recognition of GAS by macrophages. Data described in the fourth part of my thesis suggest that S. pyogenes is recognized by macrophages independently of the most commonly TLRs used to recognize gram-positive pathogens, TLR2, TLR4 and TLR9 and their combination. However, the signaling events observed in macrophages upon GAS infection were still dependent on the TLR-adaptor MyD88. Surprisingly, IFN production was independent of the GAS cytolysins, SLS and SLO, often required in other gram-positive bacteria. Overall our data indicate that GAS is recognized by a MyD88-dependent receptor other than those commonly used to detect bacteria and reveal a new type of bacterial recognition for the production of type I IFN

Role of simulation in open varicose veins surgery: A systematic review

Objective: To assess the types and effectiveness of simulators present for open varicose vein surgery. Methods: The systematic review was conducted at The Aga Khan University Hospital Karachi and comprised studies published from 1st January 2000 to 30th June 2020 related to open varicose vein surgical procedures done on simulators. Databases searched were PubMed, Medline, Google Scholar, Cochrane and Scopus using appropriate key words. The primary outcome of the review was to assess the effectiveness of different types of simulators used for varicose vein surgery. Results: Of the 286 articles found, 6(2%) were included. A variety of simulators ranging from animal models, homemade simulators and commercially designed models with high fidelity options had been used. Technical competence was the major domain assessed in most of the studies 5(83.3%), while 1(16.6%) study focussed on self-assessment. Blinding was done in 4(66.6%) studies for assessment purpose, and videorecording of the trainees\u27 performance was done in 5(83.3%) studies. Most studies 4(66.6%) found the use of simulation to be an effective tool in achieving technical competence. Conclusion: The use of simulation in the training of surgical residents for open varicose vein surgery was found to be beneficial, but most studies were heterogeneous in terms of design, simulator types and study participants. This makes it difficult to establish the superiority of any one type of simulator over the rest. Further research is needed to develop and validate simulators in open varicose vein surgery procedures

Rethinking connectivity as interactivity: a case study of Pakistan

Connectivity in developing countries has traditionally been viewed in terms of investment in transport and communications. This papers makes an effort to go beyond this traditional view and conceptualizes connectivity as networks between people and places. We split the overall national reforms agenda for connectivity into three prongs: a) transportation and related services, b) ICT, and c) social capital. We try to see the state of each of these three in case of Pakistan and then propose reforms keeping in view the current political economy milieu

Rethinking connectivity as interactivity: a case study of Pakistan

Connectivity in developing countries has traditionally been viewed in terms of investment in transport and communications. This papers makes an effort to go beyond this traditional view and conceptualizes connectivity as networks between people and places. We split the overall national reforms agenda for connectivity into three prongs: a) transportation and related services, b) ICT, and c) social capital. We try to see the state of each of these three in case of Pakistan and then propose reforms keeping in view the current political economy milieu

Export-led or household consumption-led growth in China: An empirical analysis

Abstract. GDP growth dependence on various factors of the country during (1980-2013) 34 years has been estimated. Ordinary Least Squares Technique of regression is applied here. The results are indicative of incidence of devaluation in the Yuan taking real effective and nominal exchange rate. Further, incidence of systematic impact of capital formation on GDP growth is greater than that of the international trade and domestic household consumption expenditure. That signifies the importance of domestic economy in contrast to the general belief of external sector dependence of the Chinese growth.Keywords. Currency devaluation, GDP growth, Regression.JEL. F13, F43, O47, E21

Aligning Corporate Strategies with the Sustainable Development Goals

The preceding three decades have been characterised by several social, technological, and environmental changes, which have customized the operational environment of corporations. One of those changes is the emergence of green sustainability (Gray, 1994; Abbas, 2019), which has an interlacing effect on creating customer value and sustaining companies’ environmental, social, and financial performance. The responses to these important issues are gaining relevance, increasing the impetus for companies to develop new business models consistent with this paradigm and share this information with external stakeholders, including the public. Such an approach will help create a holistic, integrated view of implementing sustainable development practices and foster a new culture consistent with a large-scale transition to a green sustainable future

Corporate strategies for sustainable development and adoption of new technologies

Technological advancements might have positive or negative impacts on sustainability. It’s essential to understand the adoption of these technologies to achieve better sustainability. The United Nations 2030 Agenda and the associated SDGs have been promoted as tools suitable to alleviate poverty, protect Planet Earth, and contribute to worldwide prosperity (UN, 2015; Tsalis, 2020). But governments alone cannot achieve sustainable development; they must be supported by the private sector, which plays a colossal role in advancing and achieving the SDGs. Specifically, the private sector can integrate the ‘green’ principles into their corporate strategies. This integration depends on, and requires, an effective approach to green development and the knowledge generation of SDGs as embedded in the companies’ functions, values, and day-to-day operations. The papers in this special issue investigate the role of corporate strategies for sustainable green development and knowledge generation in the implementation of the SDGs or principles by Asian and Eastern European companies from Malaysia, Vietnam, Indonesia, Emirates, Zimbabwe and Russia. Hence, there is a need to expand the research in further studies to gauge the contribution of corporate strategies towards the achievement of the SDGs in a wider group of countries. These further studies could also focus on a comparative cross-country analysis to provide insights into how institutional differences among countries influence the implementation and achievement of the SDGs. In addition, there is also a need to understand the role of other corporate strategies, including integrated reporting and long-term value, in the achievement of the SDGs. It is a matter of great importance for companies to explain how businesses create value for their key stakeholders in the long term by implementing the SDGs. The insights drawn from this special issue contribute to the existing literature and provide valuable practical information for practitioners, policymakers, and developers. Practitioners can rely on the insights provided in this special issue to make informed decisions that consider both the short-term and long-term impacts of technology solutions and their adoption in organizations. They need to consider the opportunities and challenges associated with technology adoption and develop plans to mitigate the negative impacts and maximize the positive effects of technology adoption. Additionally, policymakers can use the findings of the eight papers to establish policies and regulations that encourage the adoption of sustainable technologies that serve society while minimizing the negative impacts on the environment, economy, and the general public. Further, developers can consider the barriers identified in the analysis to develop more effective solutions. They can also incorporate sustainable practices into the development process to ensure their technologies align with sustainable development principles

Determinants and cost of production of dates in Pakistan: An analytical study

Abctract. Present study is an attempt to analyse the production determinants and the cost of production of dates using causal approach of Ordinary Least Squares Methods using secondary data. The costs associated with the agriculture production are computed from labour costs, expenses incurring on the pesticides and fertilizers and the cost of seeds and amount of rent when the piece of land is acquired on contract basis. Provision of credit facility to the farmers and growers can play a major role in softening the constraints of the farmers and motivate them to enhance production of dates. Moreover, technical and technological advancement and adoption of the cost saving technology by farmers can also help farmers improve quality and per acre yield of their production. The findings of the study suggest that the employment in agriculture sector is the most important factor affecting production of dates followed by mechanization and technological advancement and third is the credit to the farmers. All coefficients have significance of less than 0.05 with substantially large generalizability power.Keywords. Production, Technology, Credit, Dates, Finance, Growers, Labour, Costs, Fertilizers, Pesticides, Seeds.JEL. D24, J08, Q16, H81