104 research outputs found

    Toward a Clearer Understanding of Privatization

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    The trend toward privatization in higher education is clearly accelerating, as evidenced in both the scholarly and popular presses. It remains unclear whether governments cannot, or choose not to, provide sufficient resources to public postsecondary education, but intelligence points to a myriad of possible points of contention. For instance, the subprime mortgage crisis, downturns on Wall Street, declining state tax bases, and other recently emerging trends suggest little relief is in sight. Furthermore, higher education and the states most likely won\u27t be relieved by other long-term fiscal pressures. K-12 education and Medicare are frequently factors behind funding shortages. State policy continues to encourage competition not only with private institutions but also with other public institutions on a mounting set of issues. For example, Ohio created a program in which its public institutions compete for a $150 million pot of research funding (Richards, 2007). Institutions continue to compete for students and their mi tion dollars, particularly those students who have the means to pay or to use their state-based merit dollars. The competition for students will be especially acute in states, such as Colorado, that have adopted a voucher-style funding structure. Tuition and vouchers, not state block grants, have become an increasingly important source of revenue for some public research universities. States too are recognizing the funding problem and realize that if they cannot provide the resources for their institutions, they should allow them the autonomy and flexibility to set and keep their tuition and to compete for students, investments, and faculty with little state intervention

    Predictive Features of a Cockpit Traffic Display: A Workload Assessment

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    Eighteen pilots flew a series of traffic avoidance maneuvers in an experiment designed to assess the support offered and workload imposed by different levels of traffic display information in a free flight simulation. Three display prototypes were compared which differed in traffic information provided. A BASELINE (BL) display provided current and (2nd order) predicted information regarding ownship and current information of an intruder aircraft, represented on lateral and vertical displays in a coplanar suite. An INTRUDER PREDICTOR (IP) display, augmented the baseline display by providing lateral and vertical prediction of the intruder aircraft. A THREAT VECTOR (TV) display added to the IP display a vector that indicates the direction from ownship to the intruder at the predicted point of closest contact (POCC). The length of the vector corresponds to the radius of the protected zone, and the distance of the intersection of the vector with ownship predictor, corresponds to the time available till POCC or loss of separation. Pilots time shared the traffic avoidance task with a secondary task requiring them to monitor the top of the display for faint targets. This task simulated the visual demands of out-of-cockpit scanning, and hence was used to estimate the head-down time required by the different display formats. The results revealed that both display augmentations improved performance (safety) as assessed by predicted and actual loss of separation (i.e., penetration of the protected zone). Both enhancements also reduced workload, as assessed by the NASA TLX scale. The intruder predictor display produced these benefits with no substantial impact on the qualitative nature of the avoidance maneuvers that were selected. The threat vector produced the safety benefits by inducing a greater degree of (effective) lateral maneuvering, thus partially offsetting the benefits of reduced workload. The three displays did not differ in terms of their effect on performance of the monitoring task, used to infer head-down time, nor in the extent of vertical or airspeed maneuvering. The results are discussed in terms of their implications for 19 cognitive engineering design features

    In silico characterisation of the complete Ly6 protein family in Fasciola gigantica supported through transcriptomics of the newly-excysted juveniles

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    Fasciola gigantica is one of the aetiological trematodes associated with fascioliasis, which heavily impacts food-production systems and human and animal welfare on a global scale. In the absence of a vaccine, fascioliasis control and treatment is restricted to pasture management, such as clean grazing, and a limited array of chemotherapies, to which signs of resistance are beginning to appear. Research into novel control strategies is therefore urgently required and the advent of ‘omics technologies presents considerable opportunity for novel drug and vaccine target discovery. Here, interrogation of the first available F. gigantica newly excysted juvenile (NEJ) transcriptome revealed several protein families of current interest to parasitic flatworm vaccine research, including orthologues of mammalian complement regulator CD59 of the Ly6 family. Ly6 proteins have previously been identified on the tegument of Schistosoma mansoni and induced protective immunity in vaccination trials. Incorporating the recently available F. gigantica genome, the current work revealed 20 novel Ly6 family members in F. gigantica and, in parallel, significantly extended the F. hepatica complement from 3 to 18 members. Phylogenetic analysis revealed several distinct clades within the family, some of which are unique to Fasciola spp. trematodes. Analysis of available proteomic databases also revealed three of the newly discovered FhLy6s were present in extracellular vesicles, which have previously been prioritised in studying the host-parasite interface. The presentation of this new transcriptomic resource, in addition to the Ly6 family proteins here identified, represents a wealth of opportunity for future vaccine research

    Evidence of Immune Modulators in the Secretome of the Equine Tapeworm Anoplocephala perfoliata

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    Anoplocephala perfoliata is a neglected gastro-intestinal tapeworm, commonly infecting horses worldwide. Molecular investigation of A. perfoliata is hampered by a lack of tools to better understand the host–parasite interface. This interface is likely influenced by parasite derived immune modulators released in the secretome as free proteins or components of extracellular vesicles (EVs). Therefore, adult RNA was sequenced and de novo assembled to generate the first A. perfoliata transcriptome. In addition, excretory secretory products (ESP) from adult A. perfoliata were collected and EVs isolated using size exclusion chromatography, prior to proteomic analysis of the EVs, the EV surface and EV depleted ESP. Transcriptome analysis revealed 454 sequences homologous to known helminth immune modulators including two novel Sigma class GSTs, five α-HSP90s, and three α-enolases with isoforms of all three observed within the proteomic analysis of the secretome. Furthermore, secretome proteomics identified common helminth proteins across each sample with known EV markers, such as annexins and tetraspanins, observed in EV fractions. Importantly, 49 of the 454 putative immune modulators were identified across the secretome proteomics contained within and on the surface of EVs in addition to those identified in free ESP. This work provides the molecular tools for A. perfoliata to reveal key players in the host–parasite interaction within the horse host

    Proteomics and in silico approaches to extend understanding of the glutathione transferase superfamily of the tropical liver fluke Fasciola gigantica

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    Fasciolosis is an important foodborne, zoonotic disease of livestock and humans, with global annual health and economic losses estimated at several billion US$. Fasciola hepatica is the major species in temperate regions, while F. gigantica dominates in the tropics. In the absence of commercially available vaccines to control fasciolosis, increasing reports of resistance to current chemotherapeutic strategies and the spread of fasciolosis into new areas, new functional genomics approaches are being used to identify potential new drug targets and vaccine candidates. The glutathione transferase (GST) superfamily is both a candidate drug and vaccine target. This study reports the identification of a putatively novel Sigma class GST, present in a water-soluble cytosol extract from the tropical liver fluke F. gigantica. The GST was cloned and expressed as an enzymically active recombinant protein. This GST shares a greater identity with the human schistosomiasis GST vaccine currently at Phase II clinical trials than previously discovered F. gigantica GSTs, stimulating interest in its immuno-protective properties. In addition, in silico analysis of the GST superfamily of both F. gigantica and F. hepatica has revealed an additional Mu class GST, Omega class GSTs, and for the first time, a Zeta class member

    University rankings:What do they really show?

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    University rankings as developed by the media are used by many stakeholders in higher education: students looking for university places; academics looking for university jobs; university managers who need to maintain standing in the competitive arena of student recruitment; and governments who want to know that public funds spent on universities are delivering a world class higher education system. Media rankings deliberately draw attention to the performance of each university relative to all others, and as such they are undeniably simple to use and interpret. But one danger is that they are potentially open to manipulation and gaming because many of the measures underlying the rankings are under the control of the institutions themselves. This paper examines media rankings (constructed from an amalgamation of variables representing performance across numerous dimensions) to reveal the problems with using a composite index to reflect overall performance. It ends with a proposal for an alternative methodology which leads to groupings rather than point estimates

    What Counts as ‘World Class’? : Global University Rankings and Shifts in Institutional Strategies

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    Global university rankings have emerged as a benchmark of institutional success, setting standards for higher education policymaking and institutional practices. Nevertheless, only a marginal share of higher education institutions (HEI) are in a realistic position to be ranked as a ‘world-class’ institutions. In the European context, the global rankings have been used to highlight a performance gap between European and North American institutions. Here the focus has been on the HEIs in the top-100 positions, causing concerns over European higher education. This has also become a marker of world-class university. We analyze the strategies of 27 Northern European universities in different tiers to learn how they have adjusted to the reality of ranking. We conclude that the references to global rankings have increased between 2014 and 2018. At the same time, the references to rankings have become more implicit in nature. Nevertheless, we find that the discourse of global comparison and excellence has become more common in the strategies. There are also emerging references to the regional role of universities, which are apparent in the strategies of universities that are clearly outside the top-100 ranked institutions. However, this is also a reflection of the discourse of world-class university.Peer reviewe

    The Importance of pH in Regulating the Function of the Fasciola hepatica Cathepsin L1 Cysteine Protease

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    The helminth parasite Fasciola hepatica secretes cathepsin L cysteine proteases to invade its host, migrate through tissues and digest haemoglobin, its main source of amino acids. Here we investigated the importance of pH in regulating the activity and functions of the major cathepsin L protease FheCL1. The slightly acidic pH of the parasite gut facilitates the auto-catalytic activation of FheCL1 from its inactive proFheCL1 zymogen; this process was ∼40-fold faster at pH 4.5 than at pH 7.0. Active mature FheCL1 is very stable at acidic and neutral conditions (the enzyme retained ∼45% activity when incubated at 37°C and pH 4.5 for 10 days) and displayed a broad pH range for activity peptide substrates and the protein ovalbumin, peaking between pH 5.5 and pH 7.0. This pH profile likely reflects the need for FheCL1 to function both in the parasite gut and in the host tissues. FheCL1, however, could not cleave its natural substrate Hb in the pH range pH 5.5 and pH 7.0; digestion occurred only at pH≤4.5, which coincided with pH-induced dissociation of the Hb tetramer. Our studies indicate that the acidic pH of the parasite relaxes the Hb structure, making it susceptible to proteolysis by FheCL1. This process is enhanced by glutathione (GSH), the main reducing agent contained in red blood cells. Using mass spectrometry, we show that FheCL1 can degrade Hb to small peptides, predominantly of 4–14 residues, but cannot release free amino acids. Therefore, we suggest that Hb degradation is not completed in the gut lumen but that the resulting peptides are absorbed by the gut epithelial cells for further processing by intracellular di- and amino-peptidases to free amino acids that are distributed through the parasite tissue for protein anabolism

    Development of Functional Genomic Tools in Trematodes: RNA Interference and Luciferase Reporter Gene Activity in Fasciola hepatica

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    The growing availability of sequence information from diverse parasites through genomic and transcriptomic projects offer new opportunities for the identification of key mediators in the parasite–host interaction. Functional genomics approaches and methods for the manipulation of genes are essential tools for deciphering the roles of genes and to identify new intervention targets in parasites. Exciting advances in functional genomics for parasitic helminths are starting to occur, with transgene expression and RNA interference (RNAi) reported in several species of nematodes, but the area is still in its infancy in flatworms, with reports in just three species. While advancing in model organisms, there is a need to rapidly extend these technologies to other parasites responsible for several chronic diseases of humans and cattle. In order to extend these approaches to less well studied parasitic worms, we developed a test method for the presence of a viable RNAi pathway by silencing the exogenous reporter gene, firefly luciferase (fLUC). We established the method in the human blood fluke Schistosoma mansoni and then confirmed its utility in the liver fluke Fasciola hepatica. We transformed newly excysted juveniles of F. hepatica by electroporation with mRNA of fLUC and three hours later were able to detect luciferase enzyme activity, concentrated mainly in the digestive ceca. Subsequently, we tested the presence of an active RNAi pathway in F. hepatica by knocking down the exogenous luciferase activity by introduction into the transformed parasites of double-stranded RNA (dsRNA) specific for fLUC. In addition, we tested the RNAi pathway targeting an endogenous F. hepatica gene encoding leucine aminopeptidase (FhLAP), and observed a significant reduction in specific mRNA levels. In summary, these studies demonstrated the utility of RNAi targeting reporter fLUC as a reporter gene assay to establish the presence of an intact RNAi pathway in helminth parasites. These could facilitate the study of gene function and the identification of relevant targets for intervention in organisms that are by other means intractable. More specifically, these results open new perspectives for functional genomics of F. hepatica, which hopefully can lead to the development of new interventions for fascioliasis
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