335,483 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
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
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
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
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)
Going Beyond Counting First Authors in Author Co-citation Analysis
No full textThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
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
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No full textEste texto tem por objetivo estudar aproximações de lógicas, um procedimento que tem interesse tanto filosófico quanto computacional. No primeiro capítulo, é apresentado o conceito geral de aproximações. Nos três capítulos seguintes, diferentes abordagens encontradas na literatura são discutidas. Primeiro, o procedimento de Cadoli-Schaerf, que foi um dos primeiros e ainda é um dos mais importantes métodos de aproximações de lógicas, tendo servido de base para os outros dois aqui analisados. Cadoli e Schaerf trabalham com sentenças no formato normal clausal e normal negativo. O trabalho de Cadoli-Schaerf apresenta procedimentos de aproximações para lógicas proposicionais clássicas, formaliza esses procedimentos em uma lógica modal do conhecimento e os estende para modais. O segundo procedimento, de Fabio Massacci, estende Cadoli-Schaerf para sentenças proposicionais quaisquer e para sentenças modais, todas assinaladas, além disso, apresenta uma teoria da prova a partir de tableaux semânticos, também utilizando sentenças assinaladas. O terceiro procedimento, devido a Finger e Wassermann, generaliza Cadoli-Schaerf para sentenças proposicionais quaisquer não-assinaladas, empregando sentenças assinaladas apenas nos tableaux de prova. Nos dois capítulos que se seguem, é apresentada uma extensão de Finger-Wasermann para lógicas modais - c0m semântica e teoria da prova - e formaliza-se esse procedimento em uma lógica modal do conhecimento. Na conclusão, analisam-se os resultados obtidos e discutem-se possíveis direções para trabalhos futuros.not availabl
The electrified artist: Edvard Munch’s demons, treatments, and sketch of an electrotherapy session (1908–1909)
No full textIn 1908–1909, Norwegian artist Edvard Munch (1863–1944), best remembered for The Scream (1893), spent eight months under Daniel Jacobson’s care in a private nerve clinic in Copenhagen. Munch was suffering from alcohol abuse, and his signs and symptoms included auditory hallucinations, persecutory delusions, paresthesias, paralyses, violent mood swings, depression, loss of control, fatigue, and the loss of his basic ability to take care of himself. He was treated with rest, a fortifying diet, massages, baths, fresh air, limited exercise, and nonconvulsive electrotherapy. After he had settled in, Jacobson allowed Munch to draw, paint, and engage in photography. Munch responded with a portrait of Jacobson and a small but intriguing sketch of himself at one of his electrotherapy sessions. In this article, we examine the circumstances that brought Munch to Jacobson’s clinic and his therapies, with particular attention to electrotherapies. In so doing, we hope to provide a more complete picture of Munch’s crisis in 1908, his nerve doctor, the rationales for medical electricity and other treatments he endured, and Scandinavian psychiatry at this moment in time
Dispelling the Myths Behind First-author Citation Counts
No full textWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
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