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The Cryogenic Underground Observatory for Rare Events (CUORE) is a ton-scale cryogenic experiment designed to search for neutrinoless double-beta decay of 130 Te and other rare events. The CUORE detector consists of 988 TeO 2 bolometers operated underground at 10 mK in a dilution refrigerator at the Laboratori Nazionali del Gran Sasso. Candidate events are identified through a precise measurement of their energy. The absolute energy response of the detectors is established by the regular calibration of each individual bolometer using gamma sources. The close-packed configuration of the CUORE bolometer array combined with the extensive shielding surrounding the detectors requires the placement of calibration sources within the array itself. The CUORE Detector Calibration System is designed to insert radioactive sources into and remove them from the cryostat while respecting the stringent heat load, radiopurity, and operational requirements of the experiment. This paper describes the design, commissioning, and performance of this novel source calibration deployment system for ultra-low-temperature environments. [ABSTRACT FROM AUTHOR]

We consider weighted graphs with an infinite set of vertices. We show that boundedness of all functions of finite energy can be seen as a notion of ‘relative compactness’ for such graphs and study sufficient and necessary conditions for this property in terms of various metrics. We then equip graphs satisfying this property with a finite measure and investigate the associated Laplacian and its semigroup. In this context, our results include the trace class property for the semigroup, uniqueness and existence of solutions to the Dirichlet Problem with boundary arising from the natural compactification, an explicit description of the domain of the Dirichlet Laplacian, convergence of the heat semigroup for large times as well as stochastic incompleteness and transience of the corresponding random walk in continuous time. [ABSTRACT FROM AUTHOR]

Abstract: Previous studies showed higher gamma-band responses (GBRs, ≈40Hz) of the electroencephalogram (EEG) for moving compared to stationary stimuli. However, it is unclear whether this modulation by motion reflects a special responsiveness of the GBR to the stimulus feature “motion,” or whether GBR enhancements of similar magnitude can be elicited also by a salient change within a static stimulus that does not include motion. Therefore, we measured the EEG of healthy subjects watching stationary square wave gratings of high contrast that either started to move or reversed their black and white pattern shortly after their onset. The strong contrast change of the pattern reversal represented a salient but motionless change within the grating that was compared to the onset of the stationary grating and the motion onset. Induced and evoked GBRs were analyzed for all three display conditions. In order to assess the influenceof fixational eye movements on the induced GBRs, we also examined the time courses of microsaccade rates during the three display conditions. Amplitudes of both evoked and induced GBRs were stronger for pattern reversal than for motion onset. There was no significant amplitude difference between the onsets of the stationary and moving gratings. However, mean frequencies of the induced GBR were ~10Hz higher in response to the onsets of moving compared to stationary gratings. Furthermore, the modulations of the induced GBR did not parallel the modulations of microsaccade rate, indicating that our induced GBRs reflect neuronal processes. These results suggest that, within the gamma-band range, the encoding of moving gratings in early visual cortex is primarily based on an upward frequency shift, whereas contrast changes within static gratings are reflected by amplitude enhancement. [Copyright &y& Elsevier]

Abstract: The current study investigated the relevance of semantic processing and stimulus salience for memory performance in young ADHD patients and healthy control participants. 18 male ADHD patients and 15 healthy control children and adolescents participated in an ERP study during a visual memory paradigm with two different encoding tasks requiring either perceptual or semantic processing of neutral and emotional pictures. ADHD patients and healthy controls both showed a more negative slow-wave in response to task cues signalling semantic as compared to perceptual stimulus processing. In contrast to ADHD patients, healthy control children showed a larger increase in memory performance for deeply processed neutral pictures which was accompanied by a more positive mid-latency ERP component (so-called P300) after stimulus onset. Our results demonstrate that ADHD patients succeeded in allocating neural resources in preparation of different task demands. However, this increase in preparatory activation to the semantic task cue did not suffice to support successful processing and encoding of neutral stimuli to the same extent as in healthy controls. These findings provide evidence that ADHD patients show deficits in translating pre-stimulus mobilization of neural resources to successful memory formation in the absence of salient stimulus material. [Copyright &y& Elsevier]

Abstract: Gamma-band responses (GBRs) are associated with Gestalt perception processes. In the present EEG study, we investigated the effects of perceptual grouping on the visual GBR in the perimetrically intact visual field of patients with homonymous hemianopia and compared them to healthy participants. All observers were presented either random arrays of Gabor elements or arrays with an embedded circular arrangement. For the hemianopic patients, the circle was presented in their intact hemifield only. For controls, the hemifield for the circle presentation was counterbalanced across subjects. The participants were instructed to detect the circle by pressing a corresponding button. A wavelet transform based on Morlet wavelets was employed for the calculation of oscillatory GBRs. The early evoked GBR exhibited a larger amplitude and shorter latency for the healthy group compared to hemianopic patients and was associated with behavioral measures. The late total GBR between 200 and 400ms after stimulus onset was significantly increased for Gestalt-like patterns in healthy participants. This effect was not manifested in patients. The present findings indicate deficits in the early and late visual processing of Gestalt patterns even in the intact hemifield of hemianopic patients compared to healthy participants. [Copyright &y& Elsevier]

Abstract: The simultaneous recording of EEG and fMRI offers the advantage of combining precise spatial information about neuronal processing obtained by fMRI data with the high temporal resolution of EEG data. One problem for the analysis of auditory processing, however, is the noisy environment during fMRI measurements, especially when EPI sequences are employed. While EEG studies outside an MRI scanner repeatedly demonstrated a clear sound level-dependent increase of N1 amplitude, this finding was less obvious in simultaneous recordings inside a scanner. Based on the assumption that this inconsistency might be due to the confounding effect of the rather loud EPI noise, we employed a low-noise fMRI protocol. This method was previously used to reveal level-dependent fMRI activation in auditory cortex areas. We combined this method with simultaneous EEG recordings to investigate the effect of different sound intensities on the auditory evoked potentials. Eight participants without hearing deficits took part in our experiment. Frequency modulated tones (FM) were presented monaurally with two sound intensities (60 and 80 dB HL). The task of the participants was to categorize the FM-direction (rising vs. falling). Our results inside the scanner replicate the sound level dependence of AEPs from previous EEG studies outside the scanner. The data analysis revealed a significant shortening of N1 latency and an increase in the N1–P2 peak-to-peak amplitude for the higher sound intensity. On a descriptive level, the 80 dB HL stimulation yielded more activated voxels in fMRI and stronger activations. This effect was pronounced over the right hemisphere. Our results suggest that low-noise sequences might be advantageous for the examination of auditory processing in simultaneous EEG and fMRI recordings. [Copyright &y& Elsevier]

Abstract: This study proposes a standard paradigm for the investigation of visual information processing by means of gamma activity and presents a novel set of stimuli with a broad range of complex, coloured familiar real world and unfamiliar nonsense objects which are well matched with respect to physical stimulus properties. In order to demonstrate that the paradigm and stimulus set yield reliable results both were employed in two electrophysiological investigations in two independent laboratories. Participants were required to discriminate familiar from unfamiliar stimuli. The pattern of results was very consistent across laboratories. Early event-related potentials were not influenced by the stimulus type suggesting that physical stimulus properties did not confound object familiarity. Induced gamma band activity was stronger for familiar than for unfamiliar objects, supporting the notion of gamma activity as a signature of cortical networks underlying object representations. [Copyright &y& Elsevier]

The third edition of Flow Cytometry Guidelines provides the key aspects to consider when performing flow cytometry experiments and includes comprehensive sections describing phenotypes and functional assays of all major human and murine immune cell subsets. Notably, the Guidelines contain helpful tables highlighting phenotypes and key differences between human and murine cells. Another useful feature of this edition is the flow cytometry analysis of clinical samples with examples of flow cytometry applications in the context of autoimmune diseases, cancers as well as acute and chronic infectious diseases. Furthermore, there are sections detailing tips, tricks and pitfalls to avoid. All sections are written and peer-reviewed by leading flow cytometry experts and immunologists, making this edition an essential and state-of-the-art handbook for basic and clinical researchers., (© 2021 Wiley-VCH GmbH.)

Studies in animal models have shown that skin tissue-resident memory T (T RM ) cells provide enhanced and immediate effector function at the site of infection. However, analyses of skin T RM cells in humans have been hindered by the lack of an optimized isolation protocol. Here, we present a combinatorial strategy-the 6-h collagenase IV digestion and gentle tissue dissociation - for rapid and efficient isolation of skin T RM cells with skin tissue-specific immune features. In comparison with paired blood circulating memory T cells, these ex vivo isolated skin T cells express typical T RM cell markers and display higher polyfunctional properties. Moreover, these isolated cells can also be assessed for longer periods of time in ex vivo cultures. Thus, the optimized isolation protocol provides a valuable tool for further understanding of human skin T RM cells, especially for direct comparison with peripheral blood T cells at the same sample collection time., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Du, Lenz, Köhler, Zhang, Cendon, Li, Massoud, Wachtlin, Bodo, Hauser, Radbruch and Dong.)

Evoked gamma-band responses (GBRs) were shown to be involved in different aspects of human cognition and behavior. They have been linked to the integration and processing of incoming information leading to an adequate behavioral outcome. Consequently, altered evoked GBRs have been associated with impaired cognitive and behavioral states present in a variety of psychiatric disorders. However, to the best of our knowledge, there are no reports directly comparing evoked GBRs of different clinical groups in the same experimental setting. Thus, the purpose of the present study was to shed light on the question, whether evoked GBRs, as a kind of a neurophysiological biomarker of pathological states, might serve for characterization and distinguishing of groups suffering from diverse psychiatric disorders. We measured EEG during a passive auditory oddball-paradigm. Participants were patients diagnosed with schizophrenia, mood disorder, and personality disorders as well as a fourth group consisting of healthy participants. Our results indicate that evoked GBRs significantly differed from healthy participants only in schizophrenic patients whereas no difference could be observed for the other clinical groups. Our findings support the notion that early evoked GBRs could be indeed a trait variable of schizophrenia and are not a general marker of pathological brain states., (Copyright © 2010 Elsevier B.V. All rights reserved.)

Gamma-band oscillations (roughly 30-100 Hz) in human and animal EEG have received considerable attention in the past due to their correlations with cognitive processes. Here, we want to sketch how some of the higher cognitive functions can be explained by memory processes which are known to modulate gamma activity. Especially, the function of binding together the multiple features of a perceived object requires a comparison with contents stored in memory. In addition, we review recent findings about the actual behavioral relevance of human gamma-band activity. Interestingly, rather simple models of spiking neurons are not only able to generate oscillatory activity within the gamma-band range, but even show modulations of these oscillations in line with findings from human experiments., (Copyright (c) 2009 Elsevier Ltd. All rights reserved.)

Neurophysiological studies yield contrary results whether attentional problems of patients with attention-deficit/hyperactivity disorder (ADHD) are related to early visual processing deficits or not. Evoked gamma-band responses (GBRs), being among the first cortical responses occurring as early as 90ms after visual stimulation in human EEG, have been assigned a pivotal role in early visual processing. In particular, they are involved in memory matching processes and are enhanced when known stimuli are processed. The current study examined whether evoked GBR patterns during early memory matching processes could be indicative of an early visual processing deficit in ADHD patients. EEG was recorded from 13 young ADHD patients as well as 13 age-matched healthy participants. Both groups performed a simple forced choice reaction task employing line drawings of either known real-world items with representations in long-term memory or physically similar unknown items without such representations. Evoked GBRs of ADHD patients did not differentiate between known and unknown items. However, in healthy children, evoked GBRs were enhanced when stimuli matched a representation stored in memory. This finding indicates disadvantages at early visual processing stages in ADHD patients: In contrast to healthy participants, ADHD children lack an early memory based classification, possibly resulting in an impaired ability to rapidly reallocate attentional resources to relevant stimuli. These findings suggest that impaired early automatic stimulus classification in ADHD patients could be involved in deficits of selective and sustained attention., (Copyright 2010 Elsevier Ltd. All rights reserved.)

For efficient and fast encoding of our complex acoustic environment, not only aspects of bottom-up processing are significant, but rather top-down influences such as attention, memory, and anticipation promote specific behavior and perception. Neural oscillatory activity in the gamma-range (30-80 Hz) is discussed as a conceivable candidate to represent very rapid modulations of top-down factors. We investigated effects of anticipation on early gamma-band responses (GBRs) of the EEG and event-related potentials (ERPs) in response to tone sequences. These sequences were composed of six sinusoidal tones, which could be either regularly ascending or descending in frequency. Thus, the sequences reflected a good continuation of pitch, which also resulted in the buildup of strong expectancies for the upcoming stimulus within the sequence. However, some of the tone sequences contained a violation of the good continuation of pitch at the third or fifth tone position. The early phase-locked portion of the gamma-band activity was significantly increased when tones were in line with the good continuation of sequences compared to deviant tones. Further, a pronounced early negative ERP response, starting at 150 ms, was elicited by deviant tones at the third and fifth position. Our results support the notion that gamma-band oscillations reflect perceptual grouping processes of concurrent sounds and anticipatory top-down modulation, which involves some of the first stages of auditory information processing.

Gamma-hydroxybutyric acid is an emerging drug of abuse. Beside relaxation and euphoria it causes hypnosis and unconsciousness. Therefore the substance is misused as recreational drug and at drug-facilitated sexual assaults. An automated and effortless method for quantitation of gamma-hydroxybutyric acid in serum and urine was optimized and validated. Five hundred microliters sample volume are used for both matrices. The acid catalyzed conversion of gamma-hydroxybutyric acid to the corresponding gamma-butyrolactone is applied. Furthermore the method is based on headspace solid-phase dynamic extraction coupled with gas chromatography-mass spectrometry. The extraction process is performed by repeated aspiration and ejection of the headspace through a steel cannula which is coated on the inside with a polydimethylsiloxane sorbent. Thus absorption of analyte molecules by the sorbent is achieved. The influence of parameters as sorbent type, incubation temperature, number of extraction strokes, injection port temperature and injection flow speed on extraction recovery was investigated. The validation revealed good accuracy with a bias less than +/-5%. Intra- and interday precision determined at 10, 50 and 150 microg/ml for each matrix were in following ranges: 1.96-3.49% (intraday, serum), 2.38-4.31% (intraday, urine), 2.33-5.13% (interday, serum) and 2.53-5.64% (interday, urine). The method provided good linearity between 2 and 200 microg/ml yielding coefficients of determination R(2) > or = 0.9985. Limit of detection were determined at 0.16 microg/ml for serum and 0.17 microg/ml for urine, respectively. This method exhibits a fast, solvent-free and widely automated extraction process. It has been applied to toxicological routine analysis and therapeutic drug monitoring successfully.

In Europe, the misuse of gamma-hydroxybutyric acid (GHB) and its analogues has increased within the recent years. Here, 2 fatalities and 1 nonfatal intoxication resulting from ingestion of gamma-butyrolactone (GBL), a precursor of GHB, are presented. GHB was quantified involving the conversion to GBL by application of a gas chromatography-mass spectrometry (GC/MS) method. Besides quantitation of GHB equivalents ("total GBL"), all specimens of case 1 were analyzed for the metabolic precursor GBL itself (absolute GBL). The cause of death in each case was attributed to GHB intoxication; the manner of death was suicide in the first case and accidental in the second one. Another yet nonfatal GHB intoxication was reported by an emergency department concerning a 36-year-old woman who was hospitalized due to her comatose state and loss of adverse effects reflexes. Here nail polish remover pads were used as source for GBL.

We studied the effect of different contrast levels on the visual evoked gamma-band response (GBR) in order to investigate whether the GBR is modulated in a similar manner as previously reported for visual evoked potentials. Previous studies showed that the GBR can be modulated by individual characteristics (age) and experimental conditions (task difficulty, attention). However, stimulus properties, such as size and spatial frequency, also have a large impact on the GBR, which necessitates identification and control of relevant stimulus properties for optimal experimental setups. Twenty-one healthy participants were investigated during a forced-choice discrimination task. Sinusoidal gratings were presented at three contrast levels with a constant spatial frequency of 5 cycles per degree visual arc (cpd). The present data replicate the results reported for visual evoked potentials and exhibit a contrast dependent modulation of the GBR. Gamma activity is increased for higher contrast levels. These results demonstrate the importance of stimulus contrast for evoked gamma activity. Thus, it appears meaningful to control the contrast of stimuli in experiments investigating the role of gamma activity in perception and information processing.

We studied the effect of different sound intensities on the auditory evoked gamma-band response (GBR). Previous studies observed oscillatory gamma activity in the auditory cortex of animals and humans. For the visual modality, it has been demonstrated that the GBR can be modulated by top-down (attention, memory) as well as bottom-up factors (stimulus properties). Therefore, we expected to find a sound intensity modulation for the auditory GBR. 21 healthy participants without hearing deficits were investigated in a forced-choice discrimination task. Sinusoidal tones were presented at three systematically varied sound intensities (30, 45, 60 dB hearing level). The results of the auditory evoked potentials were predominantly consistent with previous studies. Furthermore, we observed an augmentation of the evoked GBR with increasing sound intensity. The analysis indicated that this intensity difference in the GBR amplitude most likely arises from increased phase-locking. The results demonstrate a distinct dependency between sound intensity and gamma-band oscillations. Future experiments that investigate the relationship between auditory evoked GBRs and higher cognitive processes should therefore select stimuli with an adequate sound intensity and control this variable to avoid confounding effects. In addition, it seems that gamma-band activity is more sensitive to exogenous stimulus parameters than evoked potentials.

Human subjects typically keep about seven items (plus or minus two) in short-term memory (STM). A theoretical neuronal model has been proposed to explain this phenomenon with physiological parameters of brain oscillations in the gamma and theta frequency range, i.e., roughly 30-80 and 4-8 Hz, respectively. In that model, STM capacity equals the number of gamma cycles (e.g., 25 ms for 40 Hz), which fit into one theta cycle (e.g., 166 ms for 6 Hz). The model is based on two assumptions: (1) theta activity should modulate gamma activity; and (2) the theta/gamma ratio should correlate with human STM capacity. The first assumption is supported by electrophysiological data showing that the amplitude of gamma oscillations is modulated by the phase of theta activity. However, so far, this has only been demonstrated for intracranial recordings. We analyzed human event-related EEG oscillations recorded in a memory experiment in which 13 subjects perceived known and unknown visual stimuli. The paradigm revealed event-related oscillations in the gamma range, which depended significantly on the phase of simultaneous theta activity. Our data are the first scalp-recorded human EEG recordings revealing a relationship between the gamma amplitude and the phase of theta oscillations, supporting the first assumption of the above-mentioned theory. Interestingly, the involved frequencies revealed a 7:1 ratio. However, this ratio does not necessarily determine human STM capacity. Since such a correlation was not explicitly tested in our paradigm, our data are not conclusive about the second assumption. Instead of theta phase modulating gamma amplitude, it is also conceivable that focal gamma activity needs to be downsampled to theta activity, before it can interact with more distant brain regions.

In recent years the cognitive functions of human gamma-band activity (30-100 Hz) advanced continuously into scientific focus. Not only bottom-up driven influences on 40 Hz activity have been observed, but also top-down processes seem to modulate responses in this frequency band. Among the various functions that have been related to gamma activity a pivotal role has been assigned to memory processes. Visual experiments suggested that gamma activity is involved in matching visual input to memory representations. Based on these findings we hypothesized that such memory related modulations of gamma activity exist in the auditory modality, as well. Thus, we chose environmental sounds for which subjects already had a long-term memory (LTM) representation and compared them to unknown, but physically similar sounds. 21 subjects had to classify sounds as 'recognized' or 'unrecognized', while EEG was recorded. Our data show significantly stronger activity in the induced gamma-band for recognized sounds in the time window between 300 and 500 ms after stimulus onset with a central topography. The results suggest that induced gamma-band activity reflects the matches between sounds and their representations in auditory LTM.