5,781 research outputs found
Disruption of the developmental programme of Trypanosoma brucei by genetic ablation of TbZFP1, a differentiation-enriched CCCH protein
No full textThe regulation of differentiation is particularly important in microbial eukaryotes that inhabit multiple environments. The parasite Trypanosoma brucei is an extreme example of this, requiring exquisite gene regulation during transmission from mammals to the tsetse fly vector. Unusually, trypanosomes rely almost exclusively on post-transcriptional mechanisms for regulated gene expression. Hence, RNA binding proteins are potentially of great significance in controlling stage-regulated processes. We have previously identified TbZFP1 as a trypanosome molecule transiently enriched during differentiation to tsetse midgut procyclic forms. This small protein (101 amino acids) contains the unusual CCCH zinc finger, an RNA binding motif. Here, we show that genetic ablation of TbZFP1 compromises repositioning of the mitochondrial genome, a specific event in the strictly regulated differentiation programme. Despite this, other events that occur both before and after this remain intact. Significantly, this phenotype correlates with the TbZFP1 expression profile during differentiation. This is the first genetic disruption of a developmental regulator in T. brucei. It demonstrates that programmed events in parasite development can be uncoupled at the molecular level. It also further supports the importance of CCCH proteins in key aspects of trypanosome cell function
Do rules control power? GATT articles and arrangements in the Uruguay Round
No full textMany complain and offer evidence that in recent years the GATT system has become more power-oriented, less stable, and less equitable. A concern to reverse this drift was one of the motives that brought the international community to agree to undertake the Uruguay Round. Rules control power, assumed the signers of the Punte del Este declaration, therefore elaborating and extending GATT rules would move the international community toward a fairer, more stable international trading system. Finger and Dhar contend that the opposite is true. Particularly in the 1980s, the elaboration and application of GATT rules has been an exercise in the application of economic and political power, not in its control. GATT rules, in theory, are there to limit national trade restrictions. Finger and Dhar contend that in fact things work the other way around: national practice comes first, and determines what the GATT rules mean. GATT's rules do not put limits on national practices, but provide international santion for these practices. Such rules are not part of the thereforelution but are part of the problem. Theirs is a situation-specific argument, say Finger and Dhar, not a generic one. Their target is not"rules", nor is it"GATT". Rather, it is the GATT rules.Rules of Origin,TF054105-DONOR FUNDED OPERATION ADMINISTRATION FEE INCOME AND EXPENSE ACCOUNT,Common Carriers Industry,Transport and Trade Logistics,Trade Policy
The unbalanced Ururguay Round outcome : the new areas in future WTO negotiations
No full textThe Uruguay Round involved a grand North-South bargain: The North reduced import barriers, particularly in textiles and agriculture. The South adopted new domestic regulations in such areas as services and intellectual property-changes that would lead to increased purchases from the North. In mercantilist economics, apples for apples-imports for imports. In real economics, apples for oranges. The authors argue that while the North's reduction of import barriers benefits both the North and the South, the new domestic regulations adopted by countries of the South could prove costly to those countries. To begin with, the regulations will be expensive to implement. And while the cost side of their impact is secured by a legal obligation (in the case of intellectual property rights, for example, the cost is higher prices for patented goods), the benefits side is not so secured.Environmental Economics&Policies,Economic Theory&Research,Payment Systems&Infrastructure,Decentralization,Rules of Origin,Economic Theory&Research,Environmental Economics&Policies,TF054105-DONOR FUNDED OPERATION ADMINISTRATION FEE INCOME AND EXPENSE ACCOUNT,Trade and Regional Integration,World Trade Organization
Mobility of the SecA 2-helix-finger is not essential for polypeptide translocation via the SecYEG complex
No full textThe bacterial ATPase SecA and protein channel complex SecYEG form the core of an essential protein translocation machinery. The nature of the conformational changes induced by each stage of the hydrolytic cycle of ATP and how they are coupled to protein translocation are not well understood. The structure of the SecA-SecYEG complex revealed a 2-helix-finger (2HF) of SecA in an ideal position to contact the substrate protein and push it through the membrane. Surprisingly, immobilization of this finger at the edge of the protein channel had no effect on translocation, whereas its imposition inside the channel blocked transport. This analysis resolves the stoichiometry of the active complex, demonstrating that after the initiation process translocation requires only one copy each of SecA and SecYEG. The results also have important implications on the mechanism of energy transduction and the power stroke driving transport. Evidently, the 2HF is not a highly mobile transducing element of polypeptide translocation
On the probability of extinction of the Haiti cholera epidemic
No full textMore than three years after its appearance in Haiti, cholera has already caused more than 8,500 deaths and 695,000 infections and it is feared to become endemic. However, no clear evidence of a stable environmental reservoir of pathogenic Vibrio cholerae, the infective agent of the disease, has emerged so far, suggesting the possibility that the transmission cycle of the disease is being maintained by bacteria freshly shed by infected individuals. Should this be the case, cholera could in principle be eradicated from Haiti. Here, we develop a framework for the estimation of the probability of extinction of the epidemic based on current information on epidemiological dynamics and health-care practice. Cholera spreading is modeled by an individual-based spatially-explicit stochastic model that accounts for the dynamics of susceptible, infected and recovered individuals hosted in different local communities connected through hydrologic and human mobility networks. Our results indicate that the probability that the epidemic goes extinct before the end of 2016 is of the order of 1 %. This low probability of extinction highlights the need for more targeted and effective interventions to possibly stop cholera in Haiti. © 2014 The Author(s)
Increased enslaving in elderly is associated with changes in neural control of the extrinsic finger muscles
No full textAging has consequences for hand motor control, among others affecting finger force enslaving during static pressing tasks. The aim of this study was to assess whether the extent of finger force enslaving changes with aging during a task that involves both static and dynamic phases. Ten right-handed young (22–30 years) and ten elderly subjects (67–79 years) were instructed to first exert a constant force (static phase) and then flex their index finger while counteracting constant resistance forces orthogonal to their fingertips (dynamic phase). The other fingers (non-instructed) were held in extension. EMG activities of the flexor digitorum superficialis (FDS) and extensor digitorum (ED) muscles in the regions corresponding to the index, middle and ring fingers together with their forces and position of index finger were measured. In both elderly and young, forces exerted by the non-instructed fingers increased (around 0.6 N for both young and elderly) during isotonic flexion of the index finger, but with a different delay of on average 100 ± 72 ms in elderly and 334 ± 101 ms in young subjects. Results also suggest different responses in activity of FDS and ED muscle regions of the non-instructed fingers to index finger flexion between elderly and young subjects. The enslaving effect was significantly higher in elderly than in young subjects both in the static (12% more) and dynamic (14% more) phases. These differences in enslaving can at least partly be explained by changes in neuromuscular control.Biomechatronics & Human-Machine Contro
The measurement of vascular and neurological function in workers exposed to hand-transmitted vibration
No full textFour methods for measuring disorders of vascular function and neurological function associated with occupational exposure to hand-transmitted vibration have been defined by reference to the available literature. For measuring vascular function the methods are: i) measures of the finger systolic blood pressure (FSBP) response to local cooling and ii) measures of the finger skin temperature (FST) response to local cooling. For measuring neurological function the methods are: i) measures of vibrotactile thresholds at the fingertips and ii) measures of thermal thresholds at the fingertips.Measures of the FSBP and the FST response to cold provocation were appraised in 109 dockyard workers. The FST test did not differentiate between 82 healthy subjects and 27 subjects with vibration-induced white finger (VWF) whilst the FSBP test was found to be sensitive, specific and responsive to VWF. Vibrotactile and thermal thresholds were found to be sensitive, specific and responsive to symptoms of numbness in another study of 104 dockyard workers, of whom 67 reported neurological disorders. It was concluded that whilst the above tests could be useful for monitoring the vascular and neurological disorders, a number of improvements to the measurement methods could be worthwhile. Further experiments were carried out to investigate these improvements.The simultaneous measurement of FSBPs on multiple test fingers was developed to improve the practicality of this test when measuring FSBPs on more than one test finger. Increased central sympathetic activity was hypothesised to result from increasing the stimulus by cooling more fingers. In two experiments on 12 healthy subjects, it was found that FSBPs measured simultaneously on four test fingers gave similar results to FSBP measurements on one test finger. Simultaneous FSBP measurements on four test fingers had comparable repeatability to measurements on one test finger. It was concluded that measuring FSBPs on multiple test fingers is a useful improvement to this test.When measuring FSBPs, changing the order of presentation and the period of recovery between thermal stimuli was hypothesised to influence the results by altering central sympathetic activity. In 12 healthy subjects it was found that the order of presentation of thermal stimuli was not important but that inter-subject variability increased when recovery was allowed between thermal stimuli. It was concluded that minimising the time interval between successive applications of thermal provocation reduces undesirable inter-subject variability. Another study on 12 healthy subjects showed that different reference measurement locations give different results. It was concluded that the thumb is suitable location for making reference measurements.The FSBP test and the FST test both involve application of cold provocation. The two tests are sometimes performed in succession but multiple thermal provocations may have cumulative effects on central sympathetic activity. When the two vascular tests were performed in succession on 36 subjects, including 12 subjects with VWF, any effects of the order of test presentation were small although a test performed first tended to be more repeatable. It was concluded that if both tests are performed consecutively, greater emphasis should be placed on the test performed first. The data for the FST test were reanalysed and showed that the sensitivity and specificity to VWF of this test is improved by changing the method of interpreting the results. Three methods of interpreting the FST response to cold provocation that represent an improvement to the test are suggested.The two vascular tests have been shown in the literature to be repeatable for healthy subjects but not for subjects with VWF. The repeatability of the vascular tests was assessed in 36 subjects (12 manual workers, 12 office workers and 12 subjects with VWF). The repeatability of both tests was found to be low amongst workers with VWF; some of these subjects showed a negative test result on one occasion and a positive test result on another occasion. It was concluded that a repeat test may be required when a false negative result is obtained.For the vibrotactile threshold test, the skin-stimulus contact force is usually controlled. Controlling the skin indentation would simplify measurement equipment. An experiment on ten healthy subjects investigated the relationship between skin-stimulus contact force, skin indentation and vibrotactile thresholds. It was concluded that the vibrotactile threshold test could be improved by implementing control of skin-indentation. Skin indentations giving comparable vibrotactile thresholds to those obtained using controlled contact forces were identified.It is concluded that a test battery comprising the four test methods identified from the literature and subsequently developed during the course of this research can be used to monitor disorders of both vascular and neurological function associated with occupational exposure to hand-transmitted vibration. A number of recommendations are made for further improvements that might be achievable as a result of further work
Indirect sensing method for contact location and force in a compliant finger
No full textThis research presents a measurement method for a compliant gripper finger, whereby the location of the contact with an object and the exerted grasp force are measured indirectly, instead of directly on the contacting surface. For this purpose, the deformation is measured using strain gauges at two locations on the inside structure of the finger, where high deformations occur. The finger is modeled using a Finite Element Analysis, whereby strain data at the two sensor locations is gathered for a set of different contact locations. Now, by matching the measured data to a modeled scenario, both the actual contact location in this scenario and the accompanying contact force can be determined. For the experimental validation, the compliant finger embedded with the two strain gauges is manufactured and an experimental setup has been built. The results show that the contact location can be inferred from strain measurement and contact force is determined accurately up to order of magnitude of 10-1 newton. Comparing the force-deformation behavior of the original and the embedded finger, a maximum difference of 6% in actuation force was observed. Hence, the sensing method is useful to indirectly measure contact location and force for a compliant finger in contact with an object, while having a minor influence on the grasping performance of the original design.Mechanical Engineerin
The development of an endoprosthesis for the metacarpophalangeal joint
No full textRheumatoid arthritis is a painful and debilitating disease which often afflicts the key joint of the hand, the metacarpophalangeal joint. In the worst cases the diseased joint has to be replaced with an artificial joint or prosthesis. The development of the Durham metacarpophalangeal prosthesis as it was taken from prototypes through to production samples, is described in this thesis. Testing of several Durham prostheses to over 70 million cycles has been carried out on a finger function simulator and consistent wear factors of the order of 0.4 x 10(^-) (^6)mm(^3)/Nm have been measured. These wear factors for the prosthesis were also significantly lower than any found previously. Production samples of the prosthesis have been manufactured together with appropriate surgical instrumentation. Tests of the prosthesis material, cross-linked polyethylene, rubbing against itself, have been undertaken on reciprocating pin on plate rigs and again show total wear factors of the order of 0.4 x lO(^-6)mm(^3)/Nm. Interestingly, it was found that pin wear was very much less than plate wear. The pin on plate tests were extended to include ultra-high molecular weight polyethylene (UHMWPE) rubbing against UHMWPE, as well as both polyethylenes against hard counterfaces and the results are reported. A new finger function simulator has been designed, manufactured and a validation test undertaken. Having written the necessary protocol, in conjunction with clinicians and the prosthesis manufacturer, ethical approval was obtained from the local research ethics committee and the Medical Devices Agency, to permit implantation of the prosthesis in human subjects. Lastly a hand strength measurement device for pre and post operation assessment of patients has been developed and manufactured
Market access advances and retreats : the Uruguay Round and beyond
No full textIn the Uruguay Round negotiations, trade distorting agricultural policies were taken up substantively for the first time in any round of multi-lateral trade negotiations. Voluntary export restraints outside the Multifibre Arrangement (MFA) were in fact eliminated. Developing countries became equal partners with developed countries. Their tariff cuts covered as large a share of imports as those of the developed countries and were deeper. Because developing country tariffs were higher to start with, their cuts will save importers more (perdollar of imports covered) than will cuts by developed countries. Tariff bindings for most developing countries, although often above applied rates, were extended to 90 percent or more of imports. Few countries agreed to give foreigners unlimited market access in services, or full national treatment in more than a few service activities. But developed countries agreed to some liberalization of cross-border provision for 70 percent of service activities (compared with 25 percent in developing countries). Less positively, although trade restrictions on agricultural products were converted to tariffs, border protection was reduced less on agricultural than on industrial products, and there was little agreement on reducing trade-affecting subsidies. The textiles and clothing agreement binds developed countries to eliminate all MFA-sanctioned restriction but allows them to largely put off doing so until 2005. Concessions to which developing countries agreed are due now. Reciprocal concessions of particular interest are due in the future (elimination of the MFA) or yet to be negotiated (liberalization of agricultural trade). Also disquieting, since the Uruguay Round, developing countries have undertaken anti-dumping cases at a rate (per dollar of imports) three times higher than that for the United States--mostly against other developing countries.Economic Theory&Research,Rules of Origin,Export Competitiveness,Environmental Economics&Policies,Globalization and Financial Integration,TF054105-DONOR FUNDED OPERATION ADMINISTRATION FEE INCOME AND EXPENSE ACCOUNT,Environmental Economics&Policies,Rules of Origin,Export Competitiveness,World Trade Organization
- …
