Miracle-dz/UniFAR-FTUs huggingface dataset:
miR-15a/16 Regulates Macrophage Phagocytosis after Bacterial Infection

Bacterial infection and its associated sepsis are devastating clinical entities that lead to high mortality and morbidity in critically ill patients. Phagocytosis, along with other innate immune responses, exerts crucial impacts on the outcomes of these patients. MicroRNAs (miRNAs) are a novel class of regulatory noncoding RNAs that target specific mRNAs for modulation of translation and expression of a targeted protein. The roles of miRNAs in host defense against bacterial sepsis remain unclear. We found that bacterial infections and/or bacterial-derived LPS enhanced the level of miR-15a/16 in bone marrow–derived macrophages (BMDMs). Deletion of miR-15a/16 (miR-15a/16−/−) in myeloid cells significantly decreased the bacterial infection–associated mortality in sepsis mouse models. Moreover, miR-15a/16 deficiency (miR-15a/16−/−) resulted in augmented phagocytosis and generation of mitochondrial reactive oxygen species in BMDMs. Supportively, overexpression of miR-15a/16 using miRNA mimics led to decreased phagocytosis and decreased generation of mitochondrial reactive oxygen species. Mechanistically, deletion of miR-15a/16 upregulated the expression of TLR4 via targeting the principle transcriptional regulator PU.1 locating on the promoter region of TLR4, and further modulated the downstream signaling molecules of TLR4, including Rho GTPase Cdc 42 and TRAF6. In addition, deficiency of miR-15a/16 also facilitated TLR4-mediated proinflammatory cytokine/chemokine release from BMDMs at the initial phase of infections. Taken together, miR-15a/16 altered phagocytosis and bacterial clearance by targeting, at least partially, on the TLR4-associated pathways, subsequently affecting the survival of septic mice.
Lymphocyte Targeting of the Central Nervous System: A Review of Afferent and Efferent CNS‐Immune Pathways

The central nervous system (CNS) is considered to be an immunological privileged site. However, inflammatory reactions in response to virus infections, in multiple sclerosis (MS) and in experimental autoimmune encephalomyelitis (EAEl suggest that there are definite connections between the CNS and the immune system. In this review, we examine evidence for afferent and efferent pathways of communication between the CNS and the immune system, the pivotal role of regional lymph nodes in T‐cell mediated autoimmune disease of the CNS, and the factors involved in lymphocyte targeting of the CNS. Afferent pathways of lymphatic drainage of the brain are well established in a variety of species, especially rodents. Fluid and antigens appear to drain along perivascular spaces populated by immunocompetent perivascular cells. Drainage pathways connect directly via the cribriform plate to nasal lymphatics and cervical lymph nodes. Soluble antigens draining from the brain induce antibody production in the cervical lymph nodes. Using a model of cryolesion‐enhanced EAE, we review the role of lymphatic drainage and cervical lymph nodes in the enhancement of cerebral EAE. If a brain wound in the form of a cryolesion is produced 8 days post inoculation (dpi) of antigen in the induction of acute EAE, there is a 6‐fold increase in severity of cerebral EAE by 15 dpi. Removal of the cervical lymph nodes significantly reduces such enhancement of EAE. These findings suggest that drainage of antigens from the brain to the cervical lymph nodes, in the presence of activated lymphocytes in the meninges or CNS, resuIts in an enhanced second wave of lymphocytes targeting the brain. In examining the efferent immune pathway by which lymphocytes home to the CNS, several studies have characterized the phenotype of infiltrating T lymphocytes by the use of immunocy‐tochemistry or FACS analysis. T‐cells infiltrating the CNS are recently activated/memory lymphocytes typified by their high expression of CD44, LFA‐1 and ICAM‐1 and low expression of CD45RB in the mouse. Following the induction of EAE in susceptible mice, ICAM‐1 and VCAM‐1 are dramatically upregulated on CNS vessels; lymphocytes bind to such vessels via the interaction of their known ligands, LFA‐1/Mac‐1 and 1times4‐integrins, at least in vitro. It appears that 1times4‐integrin plays a key role in lymphocyte recruitment across the blood‐brain barrier and may be a major factor in lymphocyte targeting of the CNS. Definition of factors involved in the afferent and efferent connections between the CNS and the immune system may clarify mechanisms involved in immune privilege of the CNS and may open significant therapeutic opportunities for multiple sclerosis.
Estimation of Short-Run and Long-Run Elasticities of Energy Demand From Panel Data Using Shrinkage Estimators

This paper discusses the problem of obtaining short-run and long-run elasticities of energy demand for each of forty-nine states in the United States using data for twenty-one years. Estimation using the time-series data by each state gave several wrong signs for the coefficients. Estimation using pooled data was not valid because the hypothesis of homogeneity of the coefficients was rejected. Shrinkage estimators gave more reasonable results. The paper presents, in a unified framework, the classical, empirical Bayes, and Bayes approaches for deriving these estimators. Coauthors are Robert P. Trost, Hongyi Li, and Frederick Joutz.
Marked Decline in Atmospheric Carbon Dioxide Concentrations During the Paleogene

The relation between the partial pressure of atmospheric carbon dioxide (pCO2) and Paleogene climate is poorly resolved. We used stable carbon isotopic values of di-unsaturated alkenones extracted from deep sea cores to reconstruct pCO2 fromthe middle Eocene to the late Oligocene (∼45 to 25 million years ago). Our results demonstrate that pCO2 ranged between 1000 to 1500 parts per million by volume in the middle to late Eocene, then decreased in several steps during the Oligocene, and reached modern levels by the latest Oligocene. The fall in pCO2 likely allowed for a critical expansion of ice sheets on Antarctica and promoted conditions that forced the onset of terrestrial C4 photosynthesis.
Client perceived value within ISO 9000 consultancy projects

For many small and medium‐sized enterprises (SMEs), quality systems, and ISO 9000 (BS EN, ISO 9000‐1, 1994) in particular, are a fact of life. Quality systems are seen as a necessary qualification for trading in certain markets. This can encourage businesses to think of quality only in terms of the cheapest way to obtain a certificate, thereby failing to appreciate the organisational benefits which could be obtained if more resources were applied to the development of effective quality systems. The use of quality consultants is widespread as a means of implementing ISO 9000. The selection and use of consultants can have a major influence on the commercial impact of quality systems developed through their work. Clients do not always appreciate differences between consultants, who all promise registration. As a consequence, a client often places its trust in the cheapest consultant, the first one to come along, or a friend. This paper, which is based on a survey of SMEs registered to ISO 9000, and will be presented at the Small Business and Enterprise Development Conference, 22nd and 23rd March, 1999, explores clients’ perceptions of value through the development of a model of client‐consultant relationships. It is argued that both clients and consultants need to have awareness of these perceptions at different project stages in order to realise the benefits of consultancy relationships. Clients’ perceptions of value are identified in both the experience of the consultancy relationships as well as the outputs. By viewing client‐consultant relationship development as a process, key activities within a project can be investigated, such as initial contracting and ultimate project outputs. The paper concludes that ISO 9000 can act as a bureaucratic constraint on improvement activities, but can also provide an opportunity to develop structures and processes that help to achieve improvements in a controlled manner. It is argued that the achievement of third‐party registration is largely irrelevant to the effectiveness of a quality system in bringing about improvements, although the prospect of registration is often a necessary driver towards instigating a system. It is shown that quality consultancy relationships are perceived by clients as having widely differing outcomes. These can be both favourable and unfavourable, whilst still meeting the objective of registration.
The Path to European Integration

Observers of the European Community have criticized “intergovernmentalist” accounts for exaggerating the extent of member-state control over European integration. This article grounds these criticisms in a historical institutionalist analysis, stressing the need to study European integration as a process that unfolds over time. Losses of control result not only from the autonomous actions of supranational organizations, but from member-state preoccupation with short-term concerns, the ubiquity of unintended consequences, and the instability of member-state policy preferences. Once gaps in control emerge, change-resistant decision rules and sunk costs associated with societal adaptations make it difficult for member states to reassert their authority. Brief examination of the evolution of EC social policy suggests the limitations of treating the EC as an instrument facilitating collective action among sovereign states. Rather, integration should be viewed as a path-dependent process producing a fragmented but discernible multitiered European polity.
Epidemics of invasive Salmonella enterica serovar enteritidis and S. enterica Serovar typhimurium infection associated with multidrug resistance among adults and children in Malawi.

BACKGROUND Nontyphoidal salmonellae (NTS) have become the most common cause of bacteremia in tropical Africa, particularly among susceptible children and HIV-infected adults. METHODS We describe 4956 episodes of NTS bacteremia (2439 episodes in adults and 2517 episodes in children) that occurred in Blantyre, Malawi, during the 7-year period 1998-2004. RESULTS A total of 75% of the cases of NTS bacteremia were due to Salmonella enterica serovar Typhimurium, and 21% were due to S. enterica serovar Enteritidis. Epidemic increases in the incidence of NTS bacteremia were seen sequentially, occurring first among cases caused by S. Enteritidis and then among cases caused by S. Typhimurium. Increased incidence of bacteremia was temporally associated with the acquisition of multidrug resistance to ampicillin, cotrimoxazole, and chloramphenicol by each serovar and occurred while the incidence of infection due to other common bloodstream pathogens remained constant. These epidemics were observed among adults and children. A seasonal pattern was also seen, with increased incidence during and after the rainy season. The median age of the patients was 32 years among adults and 22 months among children. Acquisition of multidrug-resistant infection was not associated with an increased case-fatality rate among children (22%), and the case-fatality rate among adults showed a significant trend toward decreasing (from 29% to 20%). CONCLUSIONS These data have important implications for the treatment of severe febrile illness in adults and children in tropical Africa. Further understanding of the molecular basis of these epidemics of multidrug-resistant NTS infection, including ongoing whole-genome sequencing of multidrug-resistant isolates, will yield important tools for the study of NTS pathogenesis, transmission, epidemiology, and prevention.
A randomised controlled trial of postural interventions for prevention of musculoskeletal symptoms among computer users

Aims: To examine the effect of two workstation and postural interventions on the incidence of musculoskeletal symptoms among computer users. Methods: Randomised controlled trial of two distinct workstation and postural interventions (an alternate intervention and a conventional intervention) among 376 persons using computer keyboards for more than 15 hours per week. The incidence of neck/shoulder symptoms and hand/arm symptoms during six months of follow up among individuals in the intervention groups was compared to the incidence in computer users who did not receive an intervention (comparison group). For individuals in the intervention groups, study staff adjusted workstations, where possible, and trained individuals to assume the intervention postures. Individuals reported musculoskeletal symptoms in a weekly diary. Participants who reported discomfort intensity of 6 or greater on a 0–10 visual analogue scale or who reported musculoskeletal symptoms requiring use of analgesic medication were considered symptomatic. Results: There were no significant differences in the incidence of musculoskeletal symptoms among the three intervention groups. Twenty two (18.5%) participants in the alternate intervention group, 25 (20.2%) in the conventional intervention group, and 25 (21.7%) in the comparison group developed incident arm or hand symptoms. Thirty eight (33.3%) participants in the alternate intervention group, 36 (31.0%) in the conventional intervention group, and 33 (30.3%) in the comparison group developed incident neck or shoulder symptoms. Compliance with all components of the intervention was attained for only 25–38% of individuals, due mainly to the inflexibility of workstation configurations. Conclusions: This study provides evidence that two specific workplace postural interventions are unlikely to reduce the risk of upper extremity musculoskeletal symptoms among computer users.
A comparison of the forecasting ability of ARIMA models

– ARIMA models have been extensively examined in the context of the real estate market. The purpose of this paper is to examine issues relating to their application in a forecasting context. Specifically, the paper seeks to examine whether in‐sample measures of best‐fit and also past forecasting accuracy bear any relation to future forecasting performance. , – The forecasting performance of alternative ARIMA specifications are compared over rolling estimation and forecasting windows. The forecasting accuracy of the alternative specifications is compared with specific attention placed on the accuracy of the respective specification that in‐sample provides the best fitting model. , – The results highlight the limitations in using the conventional approach to identifying the best‐specified ARIMA model in sample, when the purpose of the analysis is to provide forecasts. The results show that while ARIMA models can be useful in anticipating broad market trends, there are substantial differences in the forecasts obtained using alternative specifications. The use of conventional measures of best‐fit provide little indication as to future forecasting ability, nor does the forecasting performance of a specification in previous periods. , – ARIMA modelling has frequently been highlighted as a useful forecasting approach. This paper illustrates that care needs to be paid in their use in a forecasting context and full appreciation of the strengths and limitations of the ARIMA approach.
Country Effects and Sector Effects on the Harmonization of Accounting Policy Choice

This study assesses the extent of accounting harmony in Europe prior to the recent switch to IFRS, by presuming that accounting is harmonized when ‘all firms operating in similar circumstances adopt the same accounting treatment for similar transactions regardless of their domicile’. The policies studied concern inventory, depreciation and goodwill, and the odds of using alternative accounting methods are predicted by logistic regression. The empirical results suggest that, while international exposure and firm size are significant factors, country effects are considerably greater than sector effects, which is inconsistent with harmonized accounting.
THE PURE CONVERGENCE OF KNOWLEDGE AND RIGHTS IN ECONOMIC ORGANIZATION: THE CASE OF OPEN SOURCE SOFTWARE DEVELOPMENT

The work looks at a new organization of work: open source software development. It uses a comparative analysis of institutions in conjunction with a specialization of knowledge - or competence - approach to explain the phenomenon. It mostly focuses on the stability, rather than on the existence, of the organization. It finds that open source organization can be explained by using the reasoning of the Coase Theorem; it shows that there is no empty core. Yet, what also emerges at the theoretical level is that this reasoning is, in this case, not compatible with Coase's other contribution, "The Nature of the Firm. "
Convergence of the discrete variance swap in time-homogeneous diffusion models

In stochastic volatility models based on time-homogeneous diffusions, we provide a simple necessary and sufficient condition for the discretely sampled fair strike of a variance swap to converge to the continuously sampled fair strike. It extends Theorem 3.8 of Jarrow et al. [Discretely sampled variance and volatility swaps versus their continuous approximations. Financ. Stoch. , 2013, 17(2), 305–324]. In particular, it gives an affirmative answer to a problem posed in that paper in the case of the stochastic volatility model. We also give precise conditions (not based on asymptotics) when the discrete fair strike of the variance swap is higher than the continuous one and discuss the convex order conjecture proposed by Griessler and Keller-Ressel [Convex order of discrete, continuous and predictable quadratic variation and applications to options on variance. SIAM J. Financ. Math., 2014, 5(1), 1–19] in this context.
The Prince and the Pauper? CEO Pay in the United States and United Kingdom

We document differences in CEO pay and incentives in the United States and the United Kingdom for 1997. After controlling for size, sector and other firm and executive characteristics, CEOs in the US earn 45% higher cash compensation and 190% higher total compensation. The calculated effective ownership percentage in the US implies that the median CEO receives 1.48% of any increase in shareholder wealth compared to 0.25% in the UK The differences, can be largely attributed to greater share option awards in the US arising from, institutional and cultural differences between the two countries.
Kicking the Habit

Our collective bias has been to study large, publicly traded companies. Not only do these behemoths represent a tiny fraction of organizations, but they have also served as uninspiring role models driven by the short-run objectives of managers and owners alike. By contrast, outstanding family-owned or family-controlled businesses, to which we have devoted relatively little attention, often outperform by marching to the beat of a different drum. They are managed for the long run. Among the most durable and best performing family businesses, this long-run approach shows up as four priorities: continuity and persistence in pursuing a substantive rather than a financial mission, exceptional attention to the internal community of employees, unusually close connection to key external stakeholders, and courageous commanding leadership that resists pressures from shortsighted owners. We would do well to learn more about these types of organizations.
The Microbial Resource Research Infrastructure MIRRI: Strength through Coordination

Microbial resources have been recognized as essential raw materials for the advancement of health and later for biotechnology, agriculture, food technology and for research in the life sciences, as their enormous abundance and diversity offer an unparalleled source of unexplored solutions. Microbial domain biological resource centres (mBRC) provide live cultures and associated data to foster and support the development of basic and applied science in countries worldwide and especially in Europe, where the density of highly advanced mBRCs is high. The not-for-profit and distributed project MIRRI (Microbial Resource Research Infrastructure) aims to coordinate access to hitherto individually managed resources by developing a pan-European platform which takes the interoperability and accessibility of resources and data to a higher level. Providing a wealth of additional information and linking to datasets such as literature, environmental data, sequences and chemistry will enable researchers to select organisms suitable for their research and enable innovative solutions to be developed. The current independent policies and managed processes will be adapted by partner mBRCs to harmonize holdings, services, training, and accession policy and to share expertise. The infrastructure will improve access to enhanced quality microorganisms in an appropriate legal framework and to resource-associated data in a more interoperable way.
Schattschneider in Brussels: How Policy Conflict Reshaped the Biotechnology Agenda in the European Union

This article asks why the European Commission lost control over the policy process in one of the most contested areas of policy-making in the European Union in recent years. The article finds that after years of vigorous political controversy over the framing of the issues at stake, the EU finally shifted into a Schattschneiderian mode of politics. The policy conflict expanded dramatically and a previously unrelated set of actors and interests united along new lines of policy debate. The analysis underscores how the political mode of EU decision-making can shift during the process of policy-making. In particular, it stresses how policy conflicts affect the mobilisation and demobilisation of political contestants and the realignment of political actors in the European Union.
Work Organization, Control and the Experience of Work in Call Centres

Despite the integration of telephone and VDU technologies, call centres are not uniform in terms of work organization. It is suggested that diversity can best be understood by reference to a range of quantitative and qualitative characteristics. Consequently, perspectives that treat all call centres as if they were the same hybrids of customization and routinization are rejected, along with over-optimistic interpretations of labour control over work organization. Empirical evidence from nine `workflows' in two call centres - an established financial sector organization and a rapidly growing outsourced operation - provide excellent grounds for an examination of similarity and difference. A picture emerges of workflows which are volume-driven and routinized, involving low levels of employee discretion, and, by contrast, those less dominated by quantitative criteria offering higher levels of operator discretion and an emphasis on the quality of customer service. Despite these distinctions, larger numbers of operators report an experience of work which is driven by quantitative imperatives, most manifest in the pervasive implementation of targets. Targets are also used increasingly to assess and mould the quality of the call centre operator's interaction with the customer. Overall, the evidence casts doubt on the optimistic perspective that call centre work, in time, will come to resemble `knowledge work'.
Promoting Resilient Livelihoods Through Adaptive Social Protection: Lessons from 124 Programmes in South Asia

Adaptive Social Protection refers to efforts to integrate social protection (SP), disaster risk reduction (DRR) and climate change adaptation (CCA), the need for which is increasingly recognised by practitioners and academics. Relying on 124 agricultural programmes implemented in five countries in Asia, this article considers how these elements are being brought together, and explores the potential gains of these linkages. It shows that full integration is still relatively limited but that, when it occurs, it helps to shift the time horizon beyond short-term interventions aimed at supporting peoples’ coping strategies and/or graduation objectives, towards longer-term interventions that can help promote transformation towards climate and disaster resilient livelihood options.