Statistical inference of the generation probability of T-cell receptors from sequence repertoires

Stochastic rearrangement of germline DNA by VDJ recombination is at the origin of immune system diversity. This process is implemented via a series of stochastic molecular events involving gene choices and random nucleotide insertions between, and deletions from, genes. We use large sequence repertoires of the variable CDR3 region of human CD4+ T-cell receptor beta chains to infer the statistical properties of these basic biochemical events. Since any given CDR3 sequence can be produced in multiple ways, the probability distribution of hidden recombination events cannot be inferred directly from the observed sequences; we therefore develop a maximum likelihood inference method to achieve this end. To separate the properties of the molecular rearrangement mechanism from the effects of selection, we focus on non-productive CDR3 sequences in T-cell DNA. We infer the joint distribution of the various generative events that occur when a new T-cell receptor gene is created. We find a rich picture of correlation (and absence thereof), providing insight into the molecular mechanisms involved. The generative event statistics are consistent between individuals, suggesting a universal biochemical process. Our distribution predicts the generation probability of any specific CDR3 sequence by the primitive recombination process, allowing us to quantify the potential diversity of the T-cell repertoire and to understand why some sequences are shared between individuals. We argue that the use of formal statistical inference methods, of the kind presented in this paper, will be essential for quantitative understanding of the generation and evolution of diversity in the adaptive immune system.Comment: 20 pages, including Appendi

Event timing in human vision : Modulating factors and independent functions

Essential for successful interaction with the environment is the human capacity to resolve events in time. Typical event timing paradigms are judgements of simultaneity (SJ) and of temporal order (TOJ). It remains unclear whether SJ and TOJ are based on the same underlying mechanism and whether there are fixed thresholds for resolution. The current study employed four visual event timing task versions: horizontal and vertical SJ and TOJ. Binary responses were analysed using multilevel binary regression modelling. Modulatory effects of potential explanatory variables on event timing perception were investigated: (1) Individual factors (sex and age), (2) temporal factors (SOA, trial number, order of experiment, order of stimuli orientation, time of day) and (3) spatial factors (left or right stimulus first, top or bottom stimulus first, horizontal vs. vertical orientation). The current study directly compares for the first time, performance on SJ and TOJ tasks using the same paradigm and presents evidence that a variety of factors and their interactions selectively modulate event timing functions in humans, explaining the variance found in previous studies. We conclude that SJ and TOJ are partially independent functions, because they are modulated differently by individual and contextual variables.Peer reviewe

Sintering and concomitant crystallization of bioactive glasses

The official meeting minutes of Bowling Green State University\u27s Board of Trustees

Is there a generalized timing impairment in Autism Spectrum Disorders across time scales and paradigms?

Individuals with ASD have abnormal motor and perceptual functions that do not currently form diagnostic criteria of ASD, but nevertheless may affect everyday behaviour. Temporal processing seems to be one of such non-diagnostic yet impaired domains, although the lack of systematic studies testing different aspects of timing in the same sample of participants prevents a conclusive assessment of whether there is a generalized temporal deficit in ASD associated with diagnostic symptoms. 17 children diagnosed with ASD and 18 typically developing age- and IQ-matched controls carried out a set of motor and perceptual timing tasks: free tapping, simultaneity judgment, auditory duration discrimination, and verbal duration estimation. Parents of participants filled in a questionnaire assessing the sense and management of time. Children with ASD showed faster and more variable free tapping than controls. Auditory duration discrimination thresholds were higher in the ASD group than controls in a sub-second version of the task, while there were no group differences in a supra-second discrimination of intervals. Children with ASD showed more variable thresholds of simultaneity judgment, and they received lower parental scores for their sense and management of time. No group differences were observed in the verbal duration estimation task in the minute-range. Different timing functions were correlated in the ASD group but not among controls, whilst several timing measures correlated with ASD symptoms. We conclude that children with ASD show a broad range of abnormalities in temporal processing tasks including motor timing, perceptual timing, and temporal perspective.</p

Is there a generalized timing impairment in Autism Spectrum Disorders across time scales and paradigms?

Individuals with ASD have abnormal motor and perceptual functions that do not currently form diagnostic criteria of ASD, but nevertheless may affect everyday behaviour. Temporal processing seems to be one of such non-diagnostic yet impaired domains, although the lack of systematic studies testing different aspects of timing in the same sample of participants prevents a conclusive assessment of whether there is a generalized temporal deficit in ASD associated with diagnostic symptoms. 17 children diagnosed with ASD and 18 typically developing age- and IQ-matched controls carried out a set of motor and perceptual timing tasks: free tapping, simultaneity judgment, auditory duration discrimination, and verbal duration estimation. Parents of participants filled in a questionnaire assessing the sense and management of time. Children with ASD showed faster and more variable free tapping than controls. Auditory duration discrimination thresholds were higher in the ASD group than controls in a sub-second version of the task, while there were no group differences in a supra-second discrimination of intervals. Children with ASD showed more variable thresholds of simultaneity judgment, and they received lower parental scores for their sense and management of time. No group differences were observed in the verbal duration estimation task in the minute-range. Different timing functions were correlated in the ASD group but not among controls, whilst several timing measures correlated with ASD symptoms. We conclude that children with ASD show a broad range of abnormalities in temporal processing tasks including motor timing, perceptual timing, and temporal perspective

Ni+-irradiated InGaAs/GaAs quantum wells: picosecond carrier dynamics

Room-temperature carrier dynamics as functions of heavy-ion implantation and subsequent thermal annealing were investigated for technologically important InGaAs/GaAs quantum wells (QWs) by means of a time-resolved up-conversion method. Sub-picosecond lifetimes were achieved at 10 MeV Ni+ doses of (20-50) x 1010 ions cm-2. The decay rates reached a maximum at the highest irradiation dose, yielding the shortest lifetime of the confined QW states of 600 fs. A simple theoretical model is proposed for the photodynamics of the carriers. The relaxation rate depended on the irradiation dose according to a power law of 1.2, while the irradiated and subsequently annealed samples exhibited a power law of 0.35. The results are qualitatively interpreted.Room-temperature carrier dynamics as functions of heavy-ion implantation and subsequent thermal annealing were investigated for technologically important InGaAs/GaAs quantum wells (QWs) by means of a time-resolved up-conversion method. Sub-picosecond lifetimes were achieved at 10 MeV Ni+ doses of (20-50) x 1010 ions cm-2. The decay rates reached a maximum at the highest irradiation dose, yielding the shortest lifetime of the confined QW states of 600 fs. A simple theoretical model is proposed for the photodynamics of the carriers. The relaxation rate depended on the irradiation dose according to a power law of 1.2, while the irradiated and subsequently annealed samples exhibited a power law of 0.35. The results are qualitatively interpreted.Room-temperature carrier dynamics as functions of heavy-ion implantation and subsequent thermal annealing were investigated for technologically important InGaAs/GaAs quantum wells (QWs) by means of a time-resolved up-conversion method. Sub-picosecond lifetimes were achieved at 10 MeV Ni+ doses of (20-50) x 1010 ions cm-2. The decay rates reached a maximum at the highest irradiation dose, yielding the shortest lifetime of the confined QW states of 600 fs. A simple theoretical model is proposed for the photodynamics of the carriers. The relaxation rate depended on the irradiation dose according to a power law of 1.2, while the irradiated and subsequently annealed samples exhibited a power law of 0.35. The results are qualitatively interpreted.Peer reviewe

Measurement of complement receptor 1 on neutrophils in bacterial and viral pneumonia

BACKGROUND: A reliable prediction of the causative agent of community-acquired pneumonia (CAP) is not possible based on clinical features. Our aim was to test, whether the measurement of the expression of complement receptors or Fcγ receptors on neutrophils and monocytes would be a useful preliminary test to differentiate between bacterial and viral pneumonia. METHODS: Sixty-eight patients with CAP were studied prospectively. Thirteen patients had pneumococcal pneumonia; 13 patients, influenza A pneumonia; 5 patients, atypical pneumonia, and 37 patients, aetiologically undefined pneumonia. Leukocyte receptor expression was measured within 2 days of hospital admission. RESULTS: The mean expression of complement receptor 1 (CR1) on neutrophils was significantly higher in the patients with pneumococcal pneumonia than in those with influenza A pneumonia. The mean expression of CR1 was also significantly higher in aetiologically undefined pneumonia than in influenza A pneumonia, but there was no difference between pneumococcal and undefined pneumonia. CONCLUSION: Our results suggest that the expression of CR1 is higher in classical bacterial pneumonia than in viral pneumonia. Determination of the expression of CR1 may be of value as an additional rapid tool in the aetiological diagnosis, bacterial or viral infection, of CAP. These results are preliminary and more research is needed to assess the utility of this new method in the diagnostics of pneumonia