353,506 research outputs found
Finger-tapping movements.
(A) A tapping action with the left thumb and index finger is performed. (B) A tapping action with the right thumb and index finger is performed. (C) Tapping with the in-phase task is performed. (D) Tapping with the anti-phase task is performed. The distance between the thumb and index finger is kept between 3 and 4 cm, and movement was performed as fast as possible for 15 s.</p
Zinc finger recombinases with adaptable DNA sequence specificity
Site-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
The 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
This 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
Shocking Fish and the Revolution They Inspired: The Birth of Modern Neurophysiology.
The books deals with the history of the research on electric fish, and particulalry with the researche that in the 18th century, from the discovery of the electric nature of the shock produced by these fish, lead to the foundation of modern electrophysiology (mainly through the work of Luigi Galvani) and to the invention of the electric battery (through Alessandro Volta
The electrified artist: Edvard Munch’s demons, treatments, and sketch of an electrotherapy session (1908–1909)
In 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
Vibration-induced white finger in dockyard employees
Vibration-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
Snake three-finger α-neurotoxins and nicotinic acetylcholine receptors: molecules, mechanisms and medicine.
Snake venom three-finger α-neurotoxins (α-3FNTx) act on postsynaptic nicotinic acetylcholine receptors (nAChRs) at the neuromuscular junction (NMJ) to produce skeletal muscle paralysis. The discovery of the archetypal α-bungarotoxin (α-BgTx), almost six decades ago, exponentially expanded our knowledge of membrane receptors and ion channels. This included the localisation, isolation and characterization of the first receptor (nAChR); and by extension, the pathophysiology and pharmacology of neuromuscular transmission and associated pathologies such as myasthenia gravis, as well as our understanding of the role of α-3FNTxs in snakebite envenomation leading to novel concepts of targeted treatment. Subsequent studies on a variety of animal venoms have yielded a plethora of novel toxins that have revolutionized molecular biomedicine and advanced drug discovery from bench to bedside. This review provides an overview of nAChRs and their subtypes, classification of α-3FNTxs and the challenges of typifying an increasing arsenal of structurally and functionally unique toxins, and the three-finger protein (3FP) fold in the context of the uPAR/Ly6/CD59/snake toxin superfamily. The pharmacology of snake α-3FNTxs including their mechanisms of neuromuscular blockade, variations in reversibility of nAChR interactions, specificity for nAChR subtypes or for distinct ligand-binding interfaces within a subtype and the role of α-3FNTxs in neurotoxic envenomation are also detailed. Lastly, a reconciliation of structure-function relationships between α-3FNTx and nAChRs, derived from historical mutational and biochemical studies and emerging atomic level structures of nAChR models in complex with α-3FNTxs is discussed.No Full Tex
Computational Methods for Analysis of the DNA-Binding Preferences of Cys2His2 Zinc-Finger Proteins
Cys(2)His(2) zinc-finger proteins (C2H2-ZFPs) constitute the largest class of human transcription factors (TFs) and also the least characterized one. Determining the DNA sequence preferences of C2H2-ZFPs is an important first step toward elucidating their roles in transcriptional regulation. Among the most promising approaches for obtaining the sequence preferences of C2H2-ZFPs are those that combine machine--learning predictions with in vivo binding maps of these proteins. Here, we provide a protocol and guidelines for predicting the DNA-binding preferences of C2H2-ZFPs from their amino acid sequences using a machine learning-based recognition code. This protocol also describes the tools and steps to combine these predictions with ChIP-seq data to remove inaccuracies, identify the zinc-finger domains within each C2H2-ZFP that engage with DNA in vivo, and pinpoint the genomic binding sites of the C2H2-ZFPs
Studium procesu Drell-Yan v experimentu Compass s využitím polarizovaného terče
Název práce: Studium procesu Drell-Yan v experimentu Compass s využitím polarizovaného terče Autor: Markéta Pešková Katedra / Ústav: Katedra fyziky nízkých teplot Vedoucí bakalářské práce: M.Sc. Michael Finger, CSc. Abstrakt: Tato práce se snaží poskytnout úvod do studií spinové struktury nukleonu. Poznání struktury nukleonu se za posledních několik desetiletí prohloubilo, ale jeho spinová struktura je stále záhadou. Polarizovaný Drell-Yan proces je jedním z konceptů, které by mohly pomoci vyřešit otázku spinu nukleonu. Měřením spinových asymetrií v tomto procesu můžeme určit spinově závislé strukturní funkce nukleonu. Následující text obsahuje úvod do teorie semi-inklusivního hlubokého nepružného rozptylu a Drell-Yan procesu. Popisuje partonové distribuční funkce (PDF) a PDF související s příčným momentem hybnosti partonů (TMD). Dále je stručně popsán způsob, jak lze pomocí Drell- Yanova procesu nalézt TMD, což je cílem Drell-Yan programu na experimentu COMPASS s použitím transverzálně polarizovaného terče a pionového svazku v letech 2014 a 2015. Práce dále popisuje spektrometr COMPASS a systém sběru a zpracování dat. Předkládáme podmínky měření při testovacím runu Drell-Yan programu v roce 2009 a při pilotním runu v roce 2014. Z těchto dat jsme zanalyzovali produkci mionového páru a kinematické...Title: Studies of Drell-Yan process with polarized target at COMPASS Author: Markéta Pešková Department / Institute: Department of Low Temperature Physics Supervisor of the bachelor thesis: M.Sc. Michael Finger, CSc. Abstract: The presented thesis intends to give an introduction into the studies of the spin structure of a nucleon. The knowledge about the structure of nucleon has grown in the last few decades; however, its spin structure is still a mystery. One of the concepts that might help solving this spin puzzle is the polarized Drell-Yan process. This process can give us the access to the spin-dependent structure functions of a nucleon via measuring spin asymmetries. In the following text, an outline of the theoretical background of the semi- inclusive Deep Inelastic Scattering and the Drell-Yan is given. The Parton Distribution Functions (PDFs) and the transverse-momentum-dependent PDFs (TMDs) are discussed. And the way of accessing the TMDs via polarized Drell-Yan process is briefly described. This is the goal of the Drell-Yan program at COMPASS experiment, using the transversely polarized target and pion beam in 2014-15. The description of experimental apparatus is given and the system of collecting and processing data is outlined. The data-taking conditions of the 2009 DY beam test and the 2014 DY...Department of Low Temperature PhysicsKatedra fyziky nízkých teplotFaculty of Mathematics and PhysicsMatematicko-fyzikální fakult
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