bluuebunny/crossref_metadata_2025 huggingface dataset:
Contribution of phosphatidylserine to membrane surface charge and protein targeting during phagosome maturation
Authors: Yeung Tony , Heit Bryan , Dubuisson Jean-Francois , Fairn Gregory D. , Chiu Basil , Inman Robert , Kapus Andras , Swanson Michele , Grinstein Sergio
Published: June 2009

During phagocytosis, the phosphoinositide content of the activated membrane decreases sharply, as does the associated surface charge, which attracts polycationic proteins. The cytosolic leaflet of the plasma membrane is enriched in phosphatidylserine (PS); however, a lack of suitable probes has precluded investigation of the fate of this phospholipid during phagocytosis. We used a recently developed fluorescent biosensor to monitor the distribution and dynamics of PS during phagosome formation and maturation. Unlike the polyphosphoinositides, PS persists on phagosomes after sealing even when other plasmalemmal components have been depleted. High PS levels are maintained through fusion with endosomes and lysosomes and suffice to attract cationic proteins like c-Src to maturing phagosomes. Phagocytic vacuoles containing the pathogens Legionella pneumophila and Chlamydia trachomatis, which divert maturation away from the endolysosomal pathway, are devoid of PS, have little surface charge, and fail to recruit c-Src. These findings highlight a function for PS in phagosome maturation and microbial killing.
Epigenetics, Wnt signaling, and stem cells: the Pygo2 connection
Authors: Horsley Valerie
Published: June 2009

Stem cells use both transcriptional and epigenetic mechanisms to control gene expression and regulate tissue development and homeostasis. In this issue, Gu et al. (Gu, B., P. Sun, Y. Yuan, R.C. Moraes, A. Li, A. Teng, A. Agrawal, C. Rhéaume, V. Bilanchone, J.M. Veltmaat, et al. 2009. J. Cell Biol. 185:811–826) reveal an important link between these two mechanisms in mammary epithelial stem cells by showing that transcriptional activation of β-catenin downstream of Wnt signaling can be regulated epigenetically through a chromatin remodeling factor, Pygo2.
Subjective Improvement in Proprioception in 2 Patients With Atypical Friedreich Ataxia Treated With Varenicline (Chantix)
Authors: Zesiewicz Theresa A , Sullivan Kelly L , Gooch Clifton L , Lynch David R
Published: June 2009

Two patients with atypical Friedreich ataxia (heterozygotes for a GAA expansion and a G130V point mutation) experienced modest proprioceptive improvements in their extremities within a month of taking varenicline (Chantix), a drug approved for smoking cessation.
Demyelinating Findings in Typical and Atypical Chronic Inflammatory Demyelinating Polyneuropathy: Sensitivity and Specificity
Authors: De Sousa Eduardo A , Chin Russell L , Sander Howard W , Latov Norman , Brannagan Thomas H
Published: June 2009

Objective:

The objective of this study was to evaluate how the number of demyelinating findings (DF) on nerve conductions affects sensitivity and specificity of electrodiagnostic criteria for chronic inflammatory demyelinating polyneuropathy (CIDP).

Methods:

Electrodiagnostic findings of 26 consecutive patients with CIDP were compared with amyotrophic lateral sclerosis (ALS) and diabetic polyneuropathy controls. Patients with CIDP were divided into typical and atypical CIDP, as defined elsewhere.

Results:

Depending on the minimal required number (MRN) of DF on nerve conductions, sensitivities decreased from an arbitrary 100% to 58% and 54%, for an MRN of 1, 2, and 3, respectively, as specificities increased, from 48% to 81% and 95%, respectively. The number of DF per patient was higher in typical CIDP than in atypical CIDP.

Conclusions:

The considerable gap between specificity and sensitivity is the reason for controversy regarding the MRN for the diagnosis of CIDP. Requiring 2 or more DFs to identify CIDP increases specificity from 48% to 81% but lowers sensitivity from 100% to 58%. For patients with other potential causes of neuropathy, the requirement of 2 or more DFs could further increase specificity.
Rituximab for the Treatment of Thymoma-Associated and De Novo Myasthenia Gravis: 3 Cases and Review
Authors: Nelson Robert P , Pascuzzi Robert M , Kessler Kenneth , Walsh Laurence E , Faught Phillip P , Ramanuja Srinivasan , Pescovitz Mark D , Loehrer Patrick J
Published: June 2009

Objectives:

Myasthenia gravis (MG) is an immune-mediated disorder associated with autoantibodies against postsynaptic nicotinic acetylcholine receptors at neuromuscular junctions. Rituximab, a monoclonal antibody specific for CD20, is used primarily to treat B-cell non-Hodgkin lymphoma. Although it has been used for treatment of a number of autoimmune diseases, there is limited experience in MG.

Methods:

Three patients with refractory MG (2 with concurrent thymoma) were given rituximab.

Results:

Symptoms stabilized and reductions in immunosuppressive medications were tolerated for extended periods, without adverse effects or infectious complications.

Conclusions:

These observations support the concept that rituximab may be helpful for the treatment of MG. Remissions in patients with or without thymoma are achievable with rituximab given in combination with commonly used modalities. Furthermore, rituximab is not necessarily contraindicated for the treatment of MG in patients being treated for thymoma. Controlled studies are called for to define its role in the treatment of refractory MG.
Facial and Trigeminal Neuropathies as the Initial Manifestation of Chronic Inflammatory Demyelinating Polyradiculopathy
Authors: Varela Heber , Rubin Devon I
Published: June 2009

Objective:

To report the clinical and electrophysiological features of a patient who presented with facial weakness and numbness as the initial manifestation of Chronic inflammatory demyelinating polyradiculopathy (CIDP).

Case Report:

An 83-year-old woman presented with facial numbness and weakness. Examination demonstrated mild facial weakness with no other cranial abnormalities. Blink and jaw-jerk reflex latencies were prolonged bilaterally; myokymic discharges were seen in the right frontalis. Cerebrospinal fluid demonstrated an elevated protein. After 3 weeks of intravenous immunoglobulin treatment, the symptoms and electrophysiological findings improved but the symptoms recurred and became more generalized after cessation of intravenous immunoglobulin.

Conclusions:

This case represents a patient with an unusual initial presentation of cranial nerve involvement in CIDP. Blink reflexes may be a useful electrophysiological technique to assess for peripheral nerve demyelination in patients with suspected CIDP.
Improvement in Aerobic Capacity After an Exercise Program in Sporadic Inclusion Body Myositis
Authors: Johnson Liam G , Collier Kelly E , Edwards Dylan J , Philippe Danielle L , Eastwood Peter R , Walters Susan E , Thickbroom Gary W , Mastaglia Frank L
Published: June 2009

Objectives:

The study aimed to investigate the effects of a combined functional and aerobic exercise program on aerobic capacity, muscle strength, and functional mobility in a group of patients with sporadic inclusion body myositis (IBM).

Methods:

Aerobic capacity, muscle strength, and functional capacity assessments were conducted on 7 participants with sporadic IBM before and after a 12-week exercise program, which included resistance exercises and aerobic stationary cycling 3 times per week on alternative days.

Results:

Aerobic capacity of the group increased significantly by 38%, and significant strength improvements were observed in 4 of the muscle groups tested (P < 0.05). The exercise program was well tolerated, and there was no significant change in the serum creatine kinase level after the exercise period.

Conclusions:

An aerobic exercise program can be safely tolerated by patients with sporadic IBM and can improve aerobic capacity and muscle strength when combined with resistance training. These findings indicate that aerobic and functional muscle strengthening exercise should be considered in the management of patients with IBM.
Multiple Cranial Neuropathy Associated With Herpes Simplex Virus Infection and Anti-GM2 Immunoglobulin M Antibodies
Authors: Santos-García Diego , Llaneza M , Macias M , Fuente-Fernández R de la
Published: June 2009

Antiganglioside antibodies can appear after several acute infections and are often associated with various clinical patterns of Guillain-Barré syndrome. Thus, for example, cytomegalovirus infection has been associated with anti-GM2 antibodies and Guillain-Barré syndrome variants with severe sensory loss and cranial nerve involvement. We report on a patient who developed multiple cranial neuropathy associated with herpes simplex virus infection and anti-GM2 immunoglobulin M antibodies.
Myasthenia Gravis With Presynaptic Electrophysiologic Abnormalities
Authors: Callaghan Brian , Moster Mark L , Bird Shawn J
Published: June 2009

Objectives:

To describe the clinical, serologic, and electrophysiologic features of 2 patients with myasthenia gravis (MG), who also had presynaptic electrophysiologic abnormalities.

Methods:

Case reports.

Results:

Two patients developed clinical symptoms consistent with MG. They lacked autonomic symptoms or signs, and their reflexes were not absent. Acetylcholine receptor antibody studies were positive, but assays for voltage-gated calcium channel antibodies were negative. Low-amplitude baseline compound muscle action potentials combined with large incremental responses immediately after exercise were consistent with a presynaptic disorder. Thymic pathology in 1 patient was characteristic of autoimmune MG showing lymphoid follicular hyperplasia. No underlying malignancy was found in either patient.

Conclusions:

Patients with MG may rarely have presynaptic electrophysiologic abnormalities. This may occur even in the absence of the typical clinical and serologic features of the Lambert-Eaton syndrome. It is possible that there is another antibody present that is modulating presynaptic acetylcholine release.
Information security: where computer science, economics and psychology meet
Authors: Anderson Ross , Moore Tyler
Published: June 2009

Until ca. 2000, information security was seen as a technological discipline, based on computer science but with mathematics helping in the design of ciphers and protocols. That perspective started to change as researchers and practitioners realized the importance of economics. As distributed systems are increasingly composed of machines that belong to principals with divergent interests, incentives are becoming as important to dependability as technical design. A thriving new field of information security economics provides valuable insights not just into ‘security’ topics such as privacy, bugs, spam and phishing, but into more general areas of system dependability and policy. This research programme has recently started to interact with psychology. One thread is in response to phishing, the most rapidly growing form of online crime, in which fraudsters trick people into giving their credentials to bogus websites; a second is through the increasing importance of security usability; and a third comes through the psychology-and-economics tradition. The promise of this multidisciplinary research programme is a novel framework for analysing information security problems—one that is both principled and effective.
Using high-resolution displays for high-resolution cardiac data
Authors: Goodyer Christopher , Hodrien John , Wood Jason , Kohl Peter , Brodlie Ken
Published: June 2009

The ability to perform fast, accurate, high-resolution visualization is fundamental to improving our understanding of anatomical data. As the volumes of data increase from improvements in scanning technology, the methods applied to visualization must evolve. In this paper, we address the interactive display of data from high-resolution magnetic resonance imaging scanning of a rabbit heart and subsequent histological imaging. We describe a visualization environment involving a tiled liquid crystal display panel display wall and associated software, which provides an interactive and intuitive user interface. TheoViewsoftware is an OpenGL application that is written for theVR Jugglerenvironment. This environment abstracts displays and devices away from the application itself, aiding portability between different systems, from desktop PCs to multi-tiled display walls. Portability between display walls has been demonstrated through its use on walls at the universities of both Leeds and Oxford. We discuss important factors to be considered for interactive two-dimensional display of large three-dimensional datasets, including the use of intuitive input devices and level of detail aspects.
Engineering design optimization using services and workflows
Authors: Crick Tom , Dunning Peter , Kim Hyunsun , Padget Julian
Published: June 2009

Multi-disciplinary design optimization (MDO) is the process whereby the often conflicting requirements of the different disciplines to the engineering design process attempts to converge upon a description that represents an acceptable compromise in the design space. We present a simple demonstrator of a flexible workflow framework for engineering design optimization using an e-Science tool. This paper provides a concise introduction to MDO, complemented by a summary of the related tools and techniques developed under the umbrella of the UK e-Science programme that we have explored in support of the engineering process. The main contributions of this paper are: (i) a description of the optimization workflow that has been developed in theTavernaworkbench, (ii) a demonstrator of a structural optimization process with a range of tool options using common benchmark problems, (iii) some reflections on the experience of software engineering meeting mechanical engineering, and (iv) an indicative discussion on the feasibility of a ‘plug-and-play’ engineering environment for analysis and design.
Multi-objective optimization of GENIE Earth system models
Authors: Price Andrew R. , Myerscough Richard J. , Voutchkov Ivan I. , Marsh Robert , Cox Simon J.
Published: June 2009

The tuning of parameters in climate models is essential to provide reliable long-term forecasts of Earth system behaviour. We apply a multi-objective optimization algorithm to the problem of parameter estimation in climate models. This optimization process involves the iterative evaluation of response surface models (RSMs), followed by the execution of multiple Earth system simulations. These computations require an infrastructure that provides high-performance computing for building and searching the RSMs and high-throughput computing for the concurrent evaluation of a large number of models. Grid computing technology is therefore essential to make this algorithm practical for members of the GENIE project.
MoSeS: Modelling and Simulation for e-Social Science
Authors: Townend Paul , Xu Jie , Birkin Mark , Turner Andy , Wu Belinda
Published: June 2009

MoSeS (Modelling and Simulation for e-Social Science) is a research node of the National Centre for e-Social Science. MoSeS uses e-Science techniques to execute an events-driven model that simulates discrete demographic processes; this allows us to project the UK population 25 years into the future. This paper describes the architecture, simulation methodology and latest results obtained by MoSeS.
Federating distributed clinical data for the prediction of adverse hypotensive events
Authors: Stell Anthony , Sinnott Richard , Jiang Jipu , Donald Rob , Chambers Iain , Citerio Giuseppe , Enblad Per , Gregson Barbara , Howells Tim , Kiening Karl , Nilsson Pelle , Ragauskas Arminas , Sahuquillo Juan , Piper Ian
Published: June 2009

The ability to predict adverse hypotensive events, where a patient's arterial blood pressure drops to abnormally low (and dangerous) levels, would be of major benefit to the fields of primary and secondary health care, and especially to the traumatic brain injury domain. A wealth of data exist in health care systems providing information on the major health indicators of patients in hospitals (blood pressure, temperature, heart rate, etc.). It is believed that if enough of these data could be drawn together and analysed in a systematic way, then a system could be built that will trigger an alarm predicting the onset of a hypotensive event over a useful time scale, e.g. half an hour in advance. In such circumstances, avoidance measures can be taken to prevent such events arising. This is the basis for the Avert-IT project (http://www.avert-it.org), a collaborative EU-funded project involving the construction of a hypotension alarm system exploiting Bayesian neural networks using techniques of data federation to bring together the relevant information for study and system development.
HIV decision support: from molecule to man
Authors: Sloot P.M.A. , Coveney Peter V. , Ertaylan G. , Müller V. , Boucher C.A. , Bubak M.
Published: June 2009

Human immunodeficiency virus (HIV) is recognized to be one of the most destructive pandemics in recorded history. Effective highly active antiretroviral therapy and the availability of genetic screening of patient virus data have led to sustained viral suppression and higher life expectancy in patients who have been infected with HIV. The sheer complexity of the disease stems from the multiscale and highly dynamic nature of the system under study. The complete cascade from genome, proteome, metabolome and physiome to health forms a multidimensional system that crosses many orders of magnitude in temporal and spatial scales. Understanding, quantifying and handling this complexity is one of the biggest challenges of our time, which requires a highly multidisciplinary approach. In order to supply researchers with an interactive framework and to provide the medical professional with appropriate tools and information for making a balanced and reliable clinical decision, we have developed ‘ViroLab’, a collaborative decision-support system (http://www.virolab.org/). ViroLab contains computational models that cover various spatial and temporal scales from atomic-level interactions in nanoseconds up to sociological interactions on the epidemiological level, spanning years of disease progression. ViroLab allows forpersonalizeddrug ranking. It is on trial in six hospitals and various virology and epidemiology laboratories across Europe.
A user-orientated approach to provenance capture and representation forin silicoexperiments, explored within the atmospheric chemistry community
Authors: Martin Chris J. , Haji Mohammed H. , Jimack Peter K. , Pilling Michael J. , Dew Peter M.
Published: June 2009

We present a novel user-orientated approach to provenance capture and representation forin silicoexperiments, contrasted against the more systems-orientated approaches that have been typical within the e-Science domain. In our approach, we seek to capture the scientist's reasoning in the form of annotations as an experiment evolves, while using the scientist's terminology in the representation of process provenance. Our user-orientated approach is applied in a case study within the atmospheric chemistry domain: we consider the design, development and evaluation of an electronic laboratory notebook, a provenance capture and storage tool, for iterative model development.
Bringing simulation to engineers in the field: a Web 2.0 approach
Authors: Haines Robert , Khan Kashif , Brooke John
Published: June 2009

Field engineers working on water distribution systems have to implement day-to-day operational decisions. Since pipe networks are highly interconnected, the effects of such decisions are correlated with hydraulic and water quality conditions elsewhere in the network. This makes the provision of predictive decision support tools (DSTs) for field engineers critical to optimizing the engineering work on the network. We describe how we created DSTs to run on lightweight mobile devices by using the Web 2.0 technique known as Software as a Service. We designed our system following the architectural style of representational state transfer. The system not only displays static geographical information system data for pipe networks, but also dynamic information and prediction of network state, by invoking and displaying the results of simulations running on more powerful remote resources.
Dancing on the Grid: using e-Science tools to extend choreographic research
Authors: Bailey Helen , Bachler Michelle , Buckingham Shum Simon , Le Blanc Anja , Popat Sita , Rowley Andrew , Turner Martin
Published: June 2009

This paper considers the role and impact of new and emerging e-Science tools on practice-led research in dance. Specifically, it draws on findings from the
e-Dance
project. This 2-year project brings together an interdisciplinary team combining research aspects of choreography, next generation of videoconferencing and human–computer interaction analysis incorporating hypermedia and nonlinear annotations for recording and documentation.
Adaptation and development of software simulation methodologies for cardiovascular engineering: present and future challenges from an end-user perspective
Authors: Díaz-Zuccarini V. , Narracott A.J. , Burriesci G. , Zervides C. , Rafiroiu D. , Jones D. , Hose D.R. , Lawford P.V.
Published: June 2009

This paper describes the use of diverse software tools in cardiovascular applications. These tools were primarily developed in the field of engineering and the applications presented push the boundaries of the software to address events related to venous and arterial valve closure, exploration of dynamic boundary conditions or the inclusion of multi-scale boundary conditions from protein to organ levels. The future of cardiovascular research and the challenges that modellers and clinicians face from validation to clinical uptake are discussed from an end-user perspective.
The OptIPuter microscopy demonstrator: enabling science through a transatlantic lightpath
Authors: Ellisman M. , Hutton T. , Kirkland A. , Lin A. , Lin C. , Molina T. , Peltier S. , Singh R. , Tang K. , Trefethen A.E. , Wallom D.C.H. , Xiong X.
Published: June 2009

The OptIPuter microscopy demonstrator project has been designed to enable concurrent and remote usage of world-class electron microscopes located in Oxford and San Diego. The project has constructed a network consisting of microscopes and computational and data resources that are all connected by a dedicated network infrastructure using the UK Lightpath and US Starlight systems. Key science drivers include examples from both materials and biological science. The resulting system is now a permanent link between the Oxford and San Diego microscopy centres. This will form the basis of further projects between the sites and expansion of the types of systems that can be remotely controlled, including optical, as well as electron, microscopy. Other improvements will include the updating of the Microsoft cluster software to the high performance computing (HPC) server 2008, which includes the HPC basic profile implementation that will enable the development of interoperable clients.
Data protection in grid-based multicentric clinical trials: killjoy or confidence-building measure?
Authors: Arning Marian , Forgó Nikolaus , Krügel Tina
Published: June 2009

In order to protect the privacy of participating patients in multicentric genetic research projects and to improve the working conditions for researchers in such projects a data protection framework needs to be installed. In the first place, all genetic data processed in the project has to be pseudonymized. In addition to that, contracts have to be concluded between the project and each project partner to guarantee that genetic data are used only within the project and that each partner complies with data security standards. Furthermore, a central data protection authority has to be installed in the project to control the partners' compliance with these contracts and to serve as a central contact point for participants. If these conditions are fulfilled, only (de facto) anonymous data are used in the project, so that data protection legislation is not directly applicable. Second, each participant has to sign a special consent form for ethical reasons and as a fallback solution if the pseudonymization of the genetic data fails. With this safety net it is possible to protect the participants' privacy and to improve the working conditions for researchers.
The inner experience of time
Authors: Wittmann Marc
Published: June 2009

The striking diversity of psychological and neurophysiological models of ‘time perception’ characterizes the debate onhowandwherein the brain time is processed. In this review, the most prominent models of time perception will be critically discussed. Some of the variation across the proposed models will be explained, namely (i) different processes and regions of the brain are involved depending on the length of the processed time interval, and (ii) different cognitive processes may be involved that are not necessarily part of a core timekeeping system but, nevertheless, influence the experience of time. These cognitive processes are distributed over the brain and are difficult to discern from timing mechanisms. Recent developments in the research on emotional influences on time perception, which succeed decades of studies on the cognition of temporal processing, will be highlighted. Empirical findings on the relationship between affect and time, together with recent conceptualizations of self- and body processes, are integrated by viewing time perception as entailing emotional and interoceptive (within the body) states. To date, specific neurophysiological mechanisms that would account for the representation of human time have not been identified. It will be argued that neural processes in the insular cortex that are related to body signals and feeling states might constitute such a neurophysiological mechanism for the encoding of duration.
Emotional moments across time: a possible neural basis for time perception in the anterior insula
Authors: Craig A.D. (Bud)
Published: June 2009

A model of awareness based on interoceptive salience is described, which has an endogenous time base that might provide a basis for the human capacity to perceive and estimate time intervals in the range of seconds to subseconds. The model posits that the neural substrate for awareness across time is located in the anterior insular cortex, which fits with recent functional imaging evidence relevant to awareness and time perception. The time base in this model is adaptive and emotional, and thus it offers an explanation for some aspects of the subjective nature of time perception. This model does not describe the mechanism of the time base, but it suggests a possible relationship with interoceptive afferent activity, such as heartbeat-related inputs.
The time–emotion paradox
Authors: Droit-Volet Sylvie , Gil Sandrine
Published: June 2009

The present manuscript discusses the time–emotion paradox in time psychology: although humans are able to accurately estimate time as if they possess a specific mechanism that allows them to measure time (i.e. an internal clock), their representations of time are easily distorted by the context. Indeed, our sense of time depends on intrinsic context, such as the emotional state, and on extrinsic context, such as the rhythm of others' activity. Existing studies on the relationships between emotion and time suggest that these contextual variations in subjective time do not result from the incorrect functioning of the internal clock but rather from the excellent ability of the internal clock to adapt to events in one's environment. Finally, the fact that we live and move in time and that everything, every act, takes more or less time has often been neglected. Thus, there is no unique, homogeneous time but instead multiple experiences of time. Our subjective temporal distortions directly reflect the way our brain and body adapt to these multiple time scales.
Impulsiveness as a timing disturbance: neurocognitive abnormalities in attention-deficit hyperactivity disorder during temporal processes and normalization with methylphenidate
Authors: Rubia Katya , Halari Rozmin , Christakou Anastasia , Taylor Eric
Published: June 2009

We argue that impulsiveness is characterized by compromised timing functions such as premature motor timing, decreased tolerance to delays, poor temporal foresight and steeper temporal discounting. A model illustration for the association between impulsiveness and timing deficits is the impulsiveness disorder of attention-deficit hyperactivity disorder (ADHD). Children with ADHD have deficits in timing processes of several temporal domains and the neural substrates of these compromised timing functions are strikingly similar to the neuropathology of ADHD. We review our published and present novel functional magnetic resonance imaging data to demonstrate that ADHD children show dysfunctions in key timing regions of prefrontal, cingulate, striatal and cerebellar location during temporal processes of several time domains including time discrimination of milliseconds, motor timing to seconds and temporal discounting of longer time intervals. Given that impulsiveness, timing abnormalities and more specifically ADHD have been related to dopamine dysregulation, we tested for and demonstrated a normalization effect of all brain dysfunctions in ADHD children during time discrimination with the dopamine agonist and treatment of choice, methylphenidate. This review together with the new empirical findings demonstrates that neurocognitive dysfunctions in temporal processes are crucial to the impulsiveness disorder of ADHD and provides first evidence for normalization with a dopamine reuptake inhibitor.
Pre-semantically defined temporal windows for cognitive processing
Authors: Pöppel Ernst
Published: June 2009

Neuronal oscillations of different frequencies are hypothesized to be basic for temporal perception; this theoretical concept provides the frame to discuss two temporal mechanisms that are thought to be essential for cognitive processing. One such mechanism operates with periods of oscillations in the range of some tens of milliseconds, and is used for complexity reduction of temporally and spatially distributed neuronal activities. Experimental evidence comes from studies on temporal-order threshold, choice reaction time, single-cell activities, evoked responses in neuronal populations or latency distributions of oculomotor responses. The other mechanism refers to pre-semantic integration in the temporal range of approximately 2–3 s. Experimental evidence comes from studies on temporal reproduction, sensorimotor synchronization, intentional movements, speech segmentation, the shift rate of ambiguous stimuli in the visual or auditory modality or the temporal modulation of the mismatch negativity. These different observations indicate the existence of a universal process of temporal integration underlying the mental machinery. This process is believed to be basic for maintenance and change of perceptual identity. Owing to the omnipresence of this kind of temporal segmentation, it is suggested to use this process for a pragmatic definition of the states of being conscious or the ‘subjective presence’.
Neural networks engaged in milliseconds and seconds time processing: evidence from transcranial magnetic stimulation and patients with cortical or subcortical dysfunction
Authors: Koch Giacomo , Oliveri Massimiliano , Caltagirone Carlo
Published: June 2009

Here, we review recent transcranial magnetic stimulation studies and investigations in patients with neurological disease such as Parkinson's disease and stroke, showing that the neural processing of time requires the activity of wide range-distributed brain networks. The neural activity of the cerebellum seems most crucial when subjects are required to quickly estimate the passage of brief intervals, and when time is computed in relation to precise salient events. Conversely, the circuits involving the striatum and the substantia nigra projecting to the prefrontal cortex (PFC) are mostly implicated in supra-second time intervals and when time is processed in conjunction with other cognitive functions. A conscious representation of temporal intervals relies on the integrity of the prefrontal and parietal cortices. The role of the PFC becomes predominant when time intervals have to be kept in memory, especially for longer supra-second time intervals, or when the task requires a high cognitive level. We conclude that the contribution of these strongly interconnected anatomical structures in time processing is not fixed, depending not only on the duration of the time interval to be assessed by the brain, but also on the cognitive set, the chosen task and the stimulus modality.
Influence of the interstimulus interval on temporal processing and learning: testing the state-dependent network model
Authors: Buonomano Dean V. , Bramen Jennifer , Khodadadifar Mahsa
Published: June 2009

The ability to determine the interval and duration of sensory events is fundamental to most forms of sensory processing, including speech and music perception. Recent experimental data support the notion that different mechanisms underlie temporal processing in the subsecond and suprasecond range. Here, we examine the predictions of one class of subsecond timing models: state-dependent networks. We establish that the interval between the comparison and the test interval, interstimulus interval (ISI), in a two-interval forced-choice discrimination task, alters the accuracy of interval discrimination but not the point of subjective equality—i.e. while timing was impaired, subjective time contraction or expansion was not observed. We also examined whether the deficit in temporal processing produced by short ISIs can be reduced by learning, and determined the generalization patterns. These results show that training subjects on a task using a short or long ISI produces dramatically different generalization patterns, suggesting different forms of perceptual learning are being engaged. Together, our results are consistent with the notion that timing in the range of hundreds of milliseconds is local as opposed to centralized, and that rapid stimulus presentation rates impair temporal discrimination. This interference is, however, decreased if the stimuli are presented to different sensory channels.
The precision of temporal judgement: milliseconds, many minutes, and beyond
Authors: Lewis P.A. , Miall R.C.
Published: June 2009

The principle that the standard deviation of estimates scales with the mean estimate, commonly known as the scalar property, is one of the most broadly accepted fundamentals of interval timing. This property is measured using the coefficient of variation (CV) calculated as the ratio between the standard deviation and the mean. In 1997, John Gibbon suggested that different time measurement mechanisms may have different levels of absolute precision, and would therefore be associated with different CVs. Here, we test this proposal by examining the CVs produced by human subjects timing a broad range of intervals (68 ms to 16.7 min). Our data reveal no evidence for multiple mechanisms, but instead show a continuous logarithmic decrease in CV as timed intervals increase. This finding joins other recent reports in demonstrating a systematic violation of the scalar property in timing data. Interestingly, the estimated CV of circadian judgements fits onto the regression of decreasing CV, suggesting a link between short interval and circadian timing mechanisms.
Relative time sharing: new findings and an extension of the resource allocation model of temporal processing
Authors: Buhusi Catalin V. , Meck Warren H.
Published: June 2009

Individuals time as if using a stopwatch that can be stopped or reset on command. Here, we review behavioural and neurobiological data supporting the time-sharing hypothesis that perceived time depends on the attentional and memory resources allocated to the timing process. Neuroimaging studies in humans suggest that timekeeping tasks engage brain circuits typically involved in attention and working memory. Behavioural, pharmacological, lesion and electrophysiological studies in lower animals support this time-sharing hypothesis. When subjects attend to a second task, or when intruder events are presented, estimated durations are shorter, presumably due to resources being taken away from timing. Here, we extend the time-sharing hypothesis by proposing that resource reallocation is proportional to the perceived contrast, both in temporal and non-temporal features, between intruders and the timed events. New findings support this extension by showing that the effect of an intruder event is dependent on the relative duration of the intruder to the intertrial interval. The conclusion is that the brain circuits engaged by timekeeping comprise not only those primarily involved in time accumulation, but also those involved in the maintenance of attentional and memory resources for timing, and in the monitoring and reallocation of those resources among tasks.
Minding time in an amodal representational space
Authors: van Wassenhove Virginie
Published: June 2009

How long did it take you to read this sentence? Chances are your response is a ball park estimate and its value depends on how fast you have scanned the text, how prepared you have been for this question, perhaps your mood or how much attention you have paid to these words. Time perception is here addressed in three sections. The first section summarizes theoretical difficulties in time perception research, specifically those pertaining to the representation of time and temporal processing. The second section reviews non-exhaustively temporal effects in multisensory perception. Sensory modalities interact in temporal judgement tasks, suggesting that (i) at some level of sensory analysis, the temporal properties across senses can be integrated in building a time percept and (ii) the representational format across senses is compatible for establishing such a percept. In the last section, a two-step analysis of temporal properties is sketched out. In the first step, it is proposed that temporal properties are automatically encoded at early stages of sensory analysis, thus providing the raw material for the building of a time percept; in the second step, time representations become available to perception through attentional gating of the raw temporal representations and via re-encoding into abstract representations.
Evaluating dedicated and intrinsic models of temporal encoding by varying context
Authors: Spencer Rebecca M.C. , Karmarkar Uma , Ivry Richard B.
Published: June 2009

Two general classes of models have been proposed to account for how people process temporal information in the milliseconds range. Dedicated models entail a mechanism in which time is explicitly encoded; examples include clock–counter models and functional delay lines. Intrinsic models, such as state-dependent networks (SDN), represent time as an emergent property of the dynamics of neural processing. An important property of SDN is that the encoding of duration is context dependent since the representation of an interval will vary as a function of the initial state of the network. Consistent with this assumption, duration discrimination thresholds for auditory intervals spanning 100 ms are elevated when an irrelevant tone is presented at varying times prior to the onset of the test interval. We revisit this effect in two experiments, considering attentional issues that may also produce such context effects. The disruptive effect of a variable context was eliminated or attenuated when the intervals between the irrelevant tone and test interval were made dissimilar or the duration of the test interval was increased to 300 ms. These results indicate how attentional processes can influence the perception of brief intervals, as well as point to important constraints for SDN models.
The experience of time: neural mechanisms and the interplay of emotion, cognition and embodiment
Authors: Wittmann Marc , van Wassenhove Virginie
Published: June 2009

Time research has been a neglected topic in the cognitive neurosciences of the last decades: how do humans perceive time? How and where in the brain is time processed? This introductory paper provides an overview of the empirical and theoretical papers on the psychological and neural basis of time perception collected in this theme issue. Contributors from the fields of cognitive psychology, psychiatry, neurology and neuroanatomy tackle this complex question with a variety of techniques ranging from psychophysical and behavioural experiments to pharmacological interventions and functional neuroimaging. Several (and some new) models of
how
and
where
in the brain time is processed are presented in this unique collection of recent research that covers experienced time intervals from milliseconds to minutes. We hope this volume to be conducive in developing a better understanding of the sense of time as part of complex set of brain–body factors that include cognitive, emotional and body states.
Is subjective duration a signature of coding efficiency?
Authors: Eagleman David M. , Pariyadath Vani
Published: June 2009

Perceived duration is conventionally assumed to correspond with objective duration, but a growing literature suggests a more complex picture. For example, repeated stimuli appear briefer in duration than a novel stimulus of equal physical duration. We suggest that such duration illusions appear to parallel the neural phenomenon of repetition suppression, and we marshal evidence for a new hypothesis: the experience of duration is a signature of the amount of energy expended in representing a stimulus, i.e. the coding efficiency. This novel hypothesis offers a unified explanation for almost a dozen illusions in the literature in which subjective duration is modulated by properties of the stimulus such as size, brightness, motion and rate of flicker.
The parietal cortex and the representation of time, space, number and other magnitudes
Authors: Bueti Domenica , Walsh Vincent
Published: June 2009

The development of sub-disciplines within cognitive neuroscience follows common sense categories such as language, audition, action, memory, emotion and perception among others. There are also well-established research programmes into temporal perception, spatial perception and mathematical cognition that also reflect the subjective impression of how experience is constructed. There is of course no reason why the brain should respect these common sense, text book divisions and, here, we discuss the contention that generalized magnitude processing is a more accurate conceptual description of how the brain deals with information about time, space, number and other dimensions. The roots of the case for linking magnitudes are based on the use to which magnitude information is put (action), the way in which we learn about magnitudes (ontogeny), shared properties and locations of magnitude processing neurons, the effects of brain lesions and behavioural interference studies. Here, we assess this idea in the context of a theory of magnitude, which proposed common processing mechanisms of time, space, number and other dimensions.
Hyphal content determines the compression strength of Candida albicans biofilms
Authors: Paramonova Ekaterina , Krom Bastiaan P. , van der Mei Henny C. , Busscher Henk J. , Sharma Prashant K.
Published: June 2009

Candida albicans is the most frequently isolated human fungal pathogen among species causing biofilm-related clinical infections. Mechanical properties of Candida biofilms have hitherto been given no attention, despite the fact that mechanical properties are important for selection of treatment or dispersal of biofilm organisms due to a bodily fluid flow. The aim of this study was to identify the factors that determine the compression strength of Candida biofilms. Biofilms of C. albicans wild-type parental strain Caf2-1, mutant strain Chk24 lacking Chk1p [known to be involved in regulation of morphogenesis (yeast-to-hyphae transition)] and gene-reconstructed strain Chk23 were evaluated for their resistance to compression, along with biofilms of Candida tropicalis GB 9/9 and Candida parapsilosis GB 2/8, derived from used voice prosthetic biofilms. Additionally, cell morphologies within the biofilm, cell-surface hydrophobicities and extracellular polymeric substance composition were determined. Our results suggest that the hyphae-to-yeast ratio influences the compression strength of C. albicans biofilms. Biofilms with a hyphal content >50 % possessed significantly higher compressive strength and were more difficult to destroy by vortexing and sonication than biofilms with a lower hyphal content. However, when the amount of extracellular DNA (eDNA) in biofilms of C. albicans Caf2-1 and Chk24 increased, biofilm strength declined, suggesting that eDNA may influence biofilm integrity adversely.
Removal of multi-heavy metals using biogenic manganese oxides generated by a deep-sea sedimentary bacterium – Brachybacterium sp. strain Mn32
Authors: Wang Wenming , Shao Zongze , Liu Yanjun , Wang Gejiao
Published: June 2009

A deep-sea manganese-oxidizing bacterium,Brachybacteriumsp. strain Mn32, showed high Mn(II) resistance (MIC 55 mM) and Mn(II)-oxidizing/removing abilities. Strain Mn32 removed Mn(II) by two pathways: (1) oxidizing soluble Mn(II) to insoluble biogenic Mn oxides – birnessite (δ-MnO2group) and manganite (γ-MnOOH); (2) the biogenic Mn oxides further adsorb more Mn(II) from the culture. The generated biogenic Mn oxides surround the cell surfaces of strain Mn32 and provide a high capacity to adsorb Zn(II) and Ni(II). Mn(II) oxidation by strain Mn32 was inhibited by both sodium azide ando-phenanthroline, suggesting the involvement of a metalloenzyme which was induced by Mn(II). X-ray diffraction analysis showed that the crystal structures of the biogenic Mn oxides were different from those of commercial pyrolusite (β-MnO2group) and fresh chemically synthesized vernadite (δ-MnO2group). The biogenic Mn oxides generated by strain Mn32 showed two to three times higher Zn(II) and Ni(II) adsorption abilities than commercial and fresh synthetic MnO2. The crystal structure and the biogenic MnO2types may be important factors for the high heavy metal adsorption ability of strain Mn32. This study provides potential applications of a new marine Mn(II)-oxidizing bacterium in heavy metal bioremediation and increases our basic knowledge of microbial manganese oxidation mechanisms.
The relevance of carbon dioxide metabolism in Streptococcus thermophilus
Authors: Arioli Stefania , Roncada Paola , Salzano Anna Maria , Deriu Francesca , Corona Silvia , Guglielmetti Simone , Bonizzi Luigi , Scaloni Andrea , Mora Diego
Published: June 2009

Streptococcus thermophilus is a major component of dairy starter cultures used for the manufacture of yoghurt and cheese. In this study, the CO2 metabolism of S. thermophilus DSM 20617T, grown in either a N2 atmosphere or an enriched CO2 atmosphere, was analysed using both genetic and proteomic approaches. Growth experiments performed in a chemically defined medium revealed that CO2 depletion resulted in bacterial arginine, aspartate and uracil auxotrophy. Moreover, CO2 depletion governed a significant change in cell morphology, and a high reduction in biomass production. A comparative proteomic analysis revealed that cells of S. thermophilus showed a different degree of energy status depending on the CO2 availability. In agreement with proteomic data, cells grown under N2 showed a significantly higher milk acidification rate compared with those grown in an enriched CO2 atmosphere. Experiments carried out on S. thermophilus wild-type and its derivative mutant, which was inactivated in the phosphoenolpyruvate carboxylase and carbamoyl-phosphate synthase activities responsible for fixing CO2 to organic molecules, suggested that the anaplerotic reactions governed by these enzymes have a central role in bacterial metabolism. Our results reveal the capnophilic nature of this micro-organism, underlining the essential role of CO2 in S. thermophilus physiology, and suggesting potential applications in dairy fermentation processes.