123,217 research outputs found
Zinc finger recombinases with adaptable DNA sequence specificity
No full textSite-specific recombinases have become essential tools in genetics and molecular biology for the precise excision or integration of DNA sequences. However, their utility is currently limited to circumstances where the sites recognized by the recombinase enzyme have been introduced into the DNA being manipulated, or natural 'pseudosites' are already present. Many new applications would become feasible if recombinase activity could be targeted to chosen sequences in natural genomic DNA. Here we demonstrate efficient site-specific recombination at several sequences taken from a 1.9 kilobasepair locus of biotechnological interest (in the bovine beta-casein gene), mediated by zinc finger recombinases (ZFRs), chimaeric enzymes with linked zinc finger (DNA recognition) and recombinase (catalytic) domains. In the "Z-sites" tested here, 22 bp casein gene sequences are flanked by 9 bp motifs recognized by zinc finger domains. Asymmetric Z-sites were recombined by the concomitant action of two ZFRs with different zinc finger DNA-binding specificities, and could be recombined with a heterologous site in the presence of a third recombinase. Our results show that engineered ZFRs may be designed to promote site-specific recombination at many natural DNA sequence
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
A finger mechanism for adaptive end effectors
No full textThis paper presents design and analysis of a rigid link finger, which may be suitable for a number of adaptive end effectors. The design has evolved from an industrial need for a tele-operated system to be used in nuclear environments. The end effector is designed to assist repair work in nuclear reactors during retrieval operation, particularly for the purpose of grasping objects of various shape, size and mass. The work is based on the University of Southampton's Whole Arm Manipulator, which has a special design consideration for safety and flexibility. The paper discusses kinematic issues associated with the finger design, and to the end of the paper specifies the limits of finger operating parameters for implementing control law
SoftGlove: Finger Vibrotactile Feedback
No full textIn this report the finger vibrotactile subsystem of the SoftGlove wearable haptic feedback glove is discussed. This system is an upgrade over the vibrotactile feedback that the current SenseGlove haptic feedback glove provides. The designed system consists of a linear resonant actuator (LRA) on each finger, which is controlled by a dedicated LRA driver over I2C. To overcome addressing limitations of the drivers, an I2C switch is used to be able to communicate with each driver individually. The system is characterized both in terms of latency and vibration strength. The peak-to-peak vibration strength is measured to be 1.44 G and a 10 % to 90 % rise and fall time of 44 ms from rest to the maximum vibration strength. Furthermore, the system is integrated with the other subsystems of the SoftGlove on a PCB.SoftgloveElectrical Engineerin
Vibration-induced white finger in dockyard employees
No full textVibration-induced white finger (VWF) is a vascular condition associated with occupational exposure to hand-transmitted vibration. The fingers are prone to intermittent blanching attacks which may be triggered by cold conditions and are usually accompanied by numbness and tingling or pain. VWF has been associated with the use of various tools and processes, among which are the percussive and rotary metal-working tools used in ship repair work. This thesis describes a study of dose-effect relationships for VWF in dockyard employees.A review of the literature revealed more than 40 epidemiological studies of VWF in workers using hand-held metal-working tools. Measurements of tool vibration have also been reported, but few researchers have combined epidemiological studies of VWF with measurements of the vibration exposures Involved. Some dose-effect relationships have been suggested and current standards contain tentative dose effect guidance. Some recent authors have suggested that the frequency weighting and time-dependencies assumed In current standards are inadequate.Methods for the measurement of hand-transmitted vibration were assessed. The vibration characteristics of sixteen pneumatic tools commonly used in dockyard work were measured in the laboratory. Repeated measurements were made In three axes at each hand position and analysis included the computation of narrow-band spectra, acceleration magnitudes in octave bands and overall frequency-weighted and unweighted acceleration magnitudes.A survey of vibration-exposed employees in a dockyard was conducted by questionnaire. Information related to symptoms of VWF, and the history of use of vibrating tools was obtained from each individual. The severity of blanching in each affected individual was recorded using a scoring system.The severity and prevalence of symptoms were related to various measures of vibration 'dose' (i.e. combinations of measured vibration magnitudes and reported exposure times) by logistic regression and survival analysis. A highly significant relationship between VWF severity and exposure time was demonstrated. However, the use of frequency-weighted acceleration in dose calculations reduced the goodness of fit, while unweighted acceleration gave a small improvement in some cases. This suggests that higher frequencies in the range 6.3 Hz to 1250 Hz are of greater Importance than current standards imply. The effect of vibration magnitude was found to be small compared with that of exposure time and no clear effect of vibration direction or vibration frequency was demonstrated.No evidence was found for a time-dependency of the form assumed in current standards. It is possible that the risk of VWF may not be directly related to the vibration magnitude, but that a 'threshold' magnitude exists, below which the hazard is small and above which it is proportional to a function of the exposure time. Further Investigation of this hypothesis is recommended
Pacinian channel mediated vasoconstriction in the fingers during vibration exposure
No full textA review of the literature showed that acute vascular responses to hand-transmitted vibration depend on the magnitude, the frequency, and the duration of the vibration but the mechanisms involved in the immediate vasoconstriction on exposure to vibration are not clear. This research was designed to advance understanding of the relation between the characteristics of vibration and changes in vascular circulation on exposed hands, and to develop a model of the mechanoreceptor channel involved in mediating vascular changes during vibration.Study 1 was designed to determine an appropriate temperature for investigating changes in finger circulation induced by hand-transmitted vibration. Subjects were exposed to vibration with two room temperatures (20°C and 28°C). The reduction in absolute finger blood flow was greater with the higher room temperature, but the percentage reduction in finger blood flow relative to FBF during pre-exposure to vibration was similar. The room temperature was then setting up at 25°C to maintain suitable absolute finger blood flow value and obtain clear reduction pattern for digits circulation during vibration exposure.Three experiments were designed to investigate the role of the Pacinian channel in mediating vasoconstriction in the fingers during exposure to 125-Hz vibration. In study 2, the association between vibration-induced reductions in finger blood flow and vibrotactile perception thresholds was investigated. Thresholds for the perception of 125-Hz vibration were measured on the thenar eminence of the right hand and then changes in finger blood flow were measured when exposed to vibration (125-Hz at 0.5 and 1.5 ms-2 r.m.s.). When the vibration magnitude was greater than individual vibration thresholds, vasoconstriction was correlated with thresholds at both vibration magnitudes. In study 3, the relation between thresholds and vasoconstriction was investigated with 125-Hz vibration and two contactors: 3-mm and 6-mm diameter probes. Subjects provided thresholds for perceiving vibration with both contact areas. With the magnitude of vibration 15 dB above each individual’s threshold with the 3-mm probe, the reduction in FBF with the 6-mm probe was greater than with the 3-mm probe. There were similar reductions in finger circulation when vibration was presented by the two sizes of contactor at the same sensation level. In study 4, the relationship between 125-Hz perception thresholds and vascular changes was investigated by applying vibration to different body locations. Vibration (125-Hz 15 dB above the individual threshold at the right thenar eminence) was applied to three body locations: right index finger, right thenar eminence, and left thenar eminence. Differences in reductions in finger blood flow caused by vibration at each location were correlated with differences in thresholds: subjects with a greater difference in threshold between fingertip and thenar eminence showed a greater difference in the vascular changes when vibration was applied to the fingertip and the thenar eminence.Study 5 investigated the role of the Pacinian channel in mediating vascular responses to vibration at different frequencies of vibration. Subjects were exposed to 10 magnitudes of vibration (from -10 dB to 40 dB sensation level) at 8, 16, 31.5, 63, 125, and 250 Hz . Finger blood flow was reduced by 63-, 125-, and 250-Hz vibration when the vibration magnitude reached a sensation level of 10 dB. With 8-, 16- and 31.5-Hzvibration, 25 dB sensation level was required to cause vasoconstriction .It is concluded that acute reductions in finger blood flow during vibration are mediated by the Pacinian channel through the sympathetic nervous reflex. The differences in the reductions in finger blood flow induced by vibration when exposed to different contact areas, body locations, and frequencies reflect the variation of the sensitivity of the Pacinian channel due to its characteristics (i.e., spatial summation, receptor density, frequency-dependent sensitivity)
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
Relation between vibrotactile perception thresholds and reductions in finger blood flow induced by vibration of the hand at frequencies in the range 8–250 Hz
No full textPurpose: this study investigated how the vasoconstriction induced by vibration depends on the frequency of vibration when the vibration magnitude is defined by individual thresholds for perceiving vibration [i.e. sensation levels (SL)].Methods: fourteen healthy subjects attended the laboratory on seven occasions: for six vibration frequencies (8, 16, 31.5, 63, 125, or 250 Hz) and a static control condition. Finger blood flow (FBF) was measured in the middle fingers of both hands at 30-second intervals during five successive periods: (i) no force or vibration, (ii) 2-N force, no vibration, (iii) 2-N force, vibration, (iv) 2-N force, no vibration, (v) no force or vibration. During period (iii), vibration was applied to the right thenar eminence via a 6-mm diameter probe during ten successive 3-min periods as the vibration magnitude increased in ten steps (?10 to +40 dB SL).Results: with vibration at 63, 125, and 250 Hz, there was vasoconstriction on both hands when the vibration magnitude reached 10 dB SL. With vibration at 8, 16, and 31.5 Hz, there was no significant vasoconstriction until the vibration reached 25 dB SL. At all frequencies, there was greater vasoconstriction with greater magnitudes of vibration.Conclusions: it is concluded that at the higher frequencies (63, 125, and 250 Hz), the Pacinian channel mediates vibrotactile sensations near threshold and vasoconstriction occurs when vibration is perceptible. At lower frequencies (8, 16, and 31.5 Hz), the Pacinian channel does not mediate sensations near threshold and vasoconstriction commences at greater magnitudes when the Pacinian channel is activate
Cut-based abduction
No full textIn this paper we explore a generalization of traditional abduction which as simultaneously perform two different tasks: (i) given an unprovable sequent Gamma proves G, find a sentence II such that Gamma, II proves G is provable (hypothesis generation); (ii) given a provable sequent Gamma proves G, find a sentence II such that Gamma proves II and the proof of Gamma, II proves G is simpler than the proof of Gamma proves G (lemma generation). We argue that the two tasks should not be distinguished, and present a general procedure for finding suitable hypotheses or lemmas. When the original sequent is provable, the abduced formula can be seen as a cut formula with respect to Gentzen's sequent calculus, so the abduction method is cut-based. Our method is based on the tablean-like system KE and we argue for its advantages over existing adduction methods based on traditional Smullyan-style Tableaux
Design of a flat dynamic hand orthosis finger for DMD patients
No full textPeople with Duchenne muscular dystrophy (DMD) will suffer from a limited hand function. Therefore, a dynamic hand orthosis could be one of the solutions to improve their hand function and quality of life. However, at this moment, none of the obtainable hand orthoses fits their special needs. The goal of this research is to design a flat dynamic hand orthosis finger for DMD patients with Brooke scale grades 4, 5, or 6 and to test its functioning. The design consists of a silicone outer part, and an inner part from polylactic acid. The presented prototype is small, can generate a flexion movement and has a finger mass of 20 g. Output forces were tested in horizontal and vertical direction and different designs were compared in relation to the bending angle. The reached output forces in horizontal and vertical direction with a certain pressure were 3.4 N (10.5 N target) at 1.75 bar and 0.6 N at 2 bar, respectively. The bending angles were 35◦ for the MCP joint, 78◦ for the PIP joint, and 58◦ for the DIP joint. To conclude, this paper presented a new design of a finger for a hand orthosis. The prototype is flat, can generate flexion movements and has a finger mass of 20 g. Except for the MCP joint, the bending angles meet the requirements. Only the output forces were too low. An outer structure of another material might solve this.Biomedical Engineerin
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