dataesr/scientific-paragraphs-categorization huggingface dataset:
Rat Paradoxical Sleep deprivation One Sprague Dawley adult rat (male, 270g) was used. The surgical procedure was the same as previously described. Briefly, four screws for EEGs were fixed on the skull bilaterally over parietal and frontal cortices and two screws over the cerebellum for references. Two EMG and two EOG electrodes, and brain and body thermistors were also implanted. At the end of the implantation procedure, the rat received a non-steroidal antiinflammatory injection (carprofene, 5mg. kg-1, S. C. ) and was allowed to recover for 7 days, during which it was weighed and monitored daily. The rat was first placed in the recording chamber for baseline recording. Data were sampled at 128 Hz except for temperature and accelerometry which were sampled at 64 Hz. The baseline signals were scored and template parameters for each state were extracted from the EEG and EMG for online sleep scoring  (Libourel et al.
The aviary was equipped with an infrared camera for video monitoring (Axis M20 Network Camera Series). The EEG, EMG, EOG and 3-axis accelerometry were recorded in logger mode at 256 Hz for 24 hours. At the end of the recordings, the bird was recaptured, the device was removed and the data collected from the SD card. All animals had ad libitum access to food and water. The aviary had a 12h/12h light-dark cycle and an ambient temperature of 20°C.
Embedded system for data acquisition ONEIROS was designed to provide a flexible set of tools, fitting in a tiny device, for the analysis of sleep in small animals. It includes an integrated, low-power electrophysiology frontend to measure up to 26 biosignals, 3 temperature signals, and 3 accelerometer axes. An additional vibrating motor can be connected to the system and controlled using either real-time or predefined sequences of variable durations and intensities of vibration to assess arousal thresholds or prevent sleep. The system can be used either as a data logger, by using an embedded media storage, or as a telemetry device for real-time monitoring and analysis of the signals. The overall hardware architecture and software embedded on the system were developed to ensure that it would match the requirements (number of channels needed and bandwidth) of various possible experimental conditions and animal species.
Software embedded on the microcontroller The software embedded on the microcontroller was developed using the Code Composer Studio integrated development environment (Texas Instrument, Inc. ). The software was written in C language, compiled using the TI compiler and transferred to the microcontroller with an EZ-FET programmer for the MSP430 microcontroller family. The role of this software is to provide flexibility and adaptability of the instrumentation to the specific needs of each experiment (i. e. the number of channels used among the 32 channels available, and a dedicated sampling frequency for each individual channel). As a result, this method of acquisition has the advantage of minimizing the power consumption of the entire system when less channels or lower sampling rates are required, thus extending the autonomy of the device for longer experiments.
At startup, the first task of the software is to detect whether the telemetry or the logger board is used for recording data and to configure the peripherals accordingly. Then the program enters an infinite loop where three different states are executed sequentially: a) retrieving the sampling rate of each channel, b) generating an acquisition sequence based on the table of sampling frequencies, and then c) indefinitely acquiring and transferring samples (following the generated sequence) until the system is stopped by power down or configuration change. If using a telemetry configuration, where data are transmitted to a remote computer, the software is able to receive real-time orders to control the vibration motor. In that case, an algorithm executed on the remote computer can automatically use the data received from the system to, for example, classify awake or sleep states of the animal and then send back vibration commands to induce sleep deprivation or to assess arousal threshold.
Based on the sampling rate defined for each channel individually, the embedded software automatically generates a sequence of acquisition at a fixed clock rate with respect to every channel frequencies. For timing precision, a 32. 768 kHz crystal oscillator is used with a drift of only 20 ppm or less. Then every possible sampling frequency that is an integer divisor of this clock  (8192, 4096, 2048, 1024, etc. ) can be set. When sent using wireless communication, data are collected using a RF remote receiver connected to a remote computer using a USB connection. The remote receiver is composed of the same transceiver chip (nRF24L01p) as the transmitter, and is associated to a PSoC 5LP (Cypress Semiconductors) microcontroller unit which transmits sampling rate configurations to the system and collects data frames which are subsequently sent to the computer through USB port.
Multiple parameters recorded in baseline condition with ONEIROS (telemetric version) in a rat To validate the design of our system (size, weight, signal quality, and autonomy), we first monitored a rat in standard lab conditions. Here, for the first time we were able to record at the same time most of the electrophysiological parameters that covary with the different states of vigilance. Fig. 9. A. illustrates 90s of raw signal recorded with ONEIROS and Fig. 9. B. shows 10s of each state. The characteristics and quantity of each state were consistent with previously published data (Fig. 10. ). During active wake (AW: dark blue), EEG and hippocampal activity is desynchronized, with the later also showing a sustained theta frequency (around 6Hz, see time frequency plot) characteristic of periods of locomotion (see also  Fig.
To our knowledge, in contrast to other commercial and/or published devices, ONEIROS is the only one that provides such flexibility in the configuration of the channels number and sampling rate, allowing users to completely customize data acquisition according to their needs. In terms of limitation, while the system is small enough to be worn by rats, it is too large to be used on smaller animals such as mice. We estimate that the device is only suitable for animals over 100g. Future efforts should be directed toward reducing the size and weight of the device further, maybe with some compromises in term of capability and flexibility. Regarding the fields of application, although the system was designed for recording sleep, it could be used for other neuroscience applications. Behavioral tasks such as mazes, novel object recognition, and fear conditioning that require freely moving animals, might also benefit from the use of ONEIROS.
Recording sleep in semi natural environment with ONEIROS By changing the wireless transmission stack to the logger stack, the device can be quickly transformed from a lab-based device to a logger suitable for recording sleep in the field. In this regard, ONEIROS does not need any additional systems to store the data (receiver, computer), as the signals are stored directly on an integrated SD card. In the logger configuration, sleep can be recorded in wild using methods previously employed with data loggers having fewer capabilities  (Rattenborg et al. , 2016). To demonstrate the feasibility of recording sleep in the field, we implanted a pigeon and recorded its vigilance states in an aviary where other birds were also housed. The instrumented bird displayed normal behavior including short flights in the 2 x 2 x 2 m aviary.
V. CONCLUSION ONEIROS was developed to record multiple aspects of sleep  (behavior, electrophysiology, metabolism)  from animals in the lab and the wild. The goal was to provide researchers with a tool that overcomes the limitations of existing wireless devices. The system provides high flexibility in terms of number of channels and sampling rate with low power consumption, allowing long-term recordings in small animals (from 100g). By wirelessly recording a rat under baseline conditions, performing a paradoxical sleep deprivation experiment in a rat, and logging data under semi-natural conditions in a pigeon, we demonstrated that ONEIROS is a useful tool for recording sleep under diverse conditions. For the first time EEG, EMG, EOG, ECG, LFPs, 3D acceleration, brain, body and ambient temperature recording, as well as homeostatic and arousal threshold experiments, can be conducted with the same system in the lab and in the wild on small animals.
Standard surgery procedures were performed by a well-experienced neurosurgeon (H. D. ,  Duffau et al. 2002 Duffau et al. , 2005)). Prior to and 3 months after surgery, functional MRI resting-state images and picture naming scores were collected. Picture naming was evaluated by a senior speech-language therapist (S. M. G. ). All participants benefited from systematic post-operative speech-language therapy during the three months post-surgery (three to five sessions per week). Patients imaging data was compared with that of 19 healthy controls (12 male, 42. 4 ± 12. 1 years; 13. 0 ± 3. 11 years of education, 18 right-handed), with no history of neurological, psychiatric or orthopedic disease, and that was comparable to the patient group in age (p = =0. 18), years of education (p = =0. 31) and gender (p = =0.
Picture naming Participants performed a picture naming task outside of the scanner. The test consists of overtly naming 80 black and white images representing various living and manufactured semantic categories (DO80,  Metz-Lutz et al. , 1991). Both categories include a comparable number of high and low frequency words, as well as an equal representation of 1 to 4 syllable words. All images are to be found in the  Snodgrass and Vanderwart picture database (1980).
Preprocessing The first five volumes of the resting state acquisitions were discarded to allow for equilibration of the magnetic field as well as patients habituation to the scanning environment. Images were preprocessed using SPM12 (http://www. fil. ion. ucl. ac. uk/spm) in MATLAB (R2012a, The Mathworks). Images were reoriented to the anterior commissure, slice-time corrected, unwrapped, realigned to the first volume, motion corrected, co-registered to the 3DT1, normalized and smoothed (FWHM 6mm filter). Note that normalization of the brain to MNI (Montreal Neurological Institute) stereotactic space is critical in the presence of tumors or resection cavities. Based on experience and previous studies a DARTEL approach was applied without tumor masking  (Ripollés et al. , 2012). Each normalized image was subsequently reviewed to detect inconsistent deformations.
Functional connectivity The functional connectivity of the resting-state network ROI that showed a correlation between change in disconnectivity and change in picture naming was evaluated using a seed-to-voxel analysis. The ROI were taken as seed, and the whole-brain was used as target (T-threshold p<0. 001, corrected at cluster level p<0. 05). Clusters were identified with the AAL toolbox (local maximum analysis,  Tzourio-Mazoyer et al. , 2002). Next, functional connectivity within each predefined resting state network was addressed using a ROI-to-ROI connectivity analysis, evaluating connectivity compared to controls, and within patients over time in relation to change in picture naming performance with the CONN functional connectivity toolbox (16a; https://www. nitrc. org/ projects/conn; Whitfield-Gabrieli and Nieto-Castanon, 2012) in Matlab R2102a, including denoising with a band-pass filter [0.
Picture naming Performance scores were collected for 34/39 participants at both time points. Of those, 16 participants decreased in performance, 11 improved and 7 showed no change after surgery. Overall, participants performed slightly worse on the picture naming test post-surgery (WSRT, p = =0. 038), with a mean score of 78. 9/80 before and 77. 4/ 80 after surgery. Unfortunately, the five patients with missing picture naming data were all left-handed. Any questions about the influence of hemispheric dominance on resting state plasticity in relation to picture naming remained unanswered.
[66] [67] [68]  Indeed, when we examined the FBR of monocytes derived from three different donors, it was found that, interestingly, different individuals exhibited varying degrees of immune responses to the same Ti microbeads (Figure  4d ). While two donors (Donors B and C) did not exhibit noticeable difference in M1/M2 differentiation of their PBMC-derived monocytes, one donor (Donar A) had strong pro-inflammatory reaction to the Ti microbeads (Figure  4e ,f), clearly indicating that there is likely a "population spectrum" of responses to the same implant possibly due to differences in receptor expressions and cytokine profiles of the immune cells. [32, 33] It should be noted that, this dataset achieved with human primary monocytes from healthy donors was different from that observed when human THP-1 monocyte cell line was used (which always showed pro-inflammatory phenotype).
Acknowledgements F. S. , M. R. , H. L. , and S. S. H. contributed equally to this work. The authors acknowledge funding from the  National Institutes of Health  ( AR057837 ,  DE021468 ,  AR068258 ,  AR066193 , and  EB022403 ). Y. S. Z. acknowledges funds from the  National Institutes of Health  ( CA201603 ,  EB026175 , and  EB025270 ) and the  New England Anti-Vivisection Society (NEAVS). This project further received funding from the  European Union 's  FP7 and Horizon 2020 research and innovation programme  under grant agreement no. 602694  (IMMODGEL) and no. 760921  (PANBioRA). S. S. R. acknowledges funding from the  National Institutes of Health  ( EB026824  and  AR074234 ). S. M. acknowledges  NEAVS  and the  American Fund for Alternatives to Animal Research (AFAAR)  for Postdoctoral Fellowship.
It applies to both somatic and gametic selection. The advantage of the population-genetics formalism is that it is less dependent on the assumption made above that a and b cells grow exponentially. Indeed, it assumes that the processes regulating population size affect both genotypes similarly. Let us apply the population genetics formalism to the normal loss of the Y chromosome with age (Figure  3 ). As mentioned above, the initial segment of the logistic curve is basically exponential. In the present context, as P 0 is close to 0 and the extent of the increase of P is small (<1. 5%), the logistic function reduces to P = P 0 e st. If we explore the same dataset as in  Veitia (2018b) , we obtain P 0 = 0. 0018 and s = 0. 024. Now, we can also compare this value of s with the difference between the specific rates of proliferation and death of X0 versus XY cells calculated according to a formalism based on ad hoc differential equations similar to those described in the Supplementary material (see details in  Veitia, 2018b).
Ethics and dissemination This study is approved by relevant institutional review boards/independent ethics committees and is conducted in accordance with the ethical principles of the Declaration of Helsinki, the European Medicines Agency guidelines of Good Clinical Practice and all other applicable regulations. Results of this study will be published in a peer-reviewed scientific journal. trial registration number NCT03085758; Pre-results. strengths and limitations of this study ► Patient selection is guided by clinical parameters, and biomarkerguided by measurement of circulating biologically active plasma adrenomedullin, allowing to select patients with an impaired outcome who may benefit most from adrecizumab therapy. ► Patients will be recruited in medical, surgical and mixed intensive care units at approximately 30 sites across four countries in Europe, promoting the studies generalisability.
MEthods And AnAlysIs design and setting AdrenOSS-2 is a phase II, randomised, double-blind, placebo-controlled, biomarker-guided, proof-of-concept and dose-finding clinical trial that is currently being conducted in patients with early septic shock and elevated concentration of circulating bio-ADM (>70 pg/mL). A total of 300 patients will be recruited in medical, surgical and mixed intensive care units (ICU) at approximately 30 sites across Belgium, France, Germany, the Netherlands and Italy (see clinicaltrials. gov of a list of current centres). Patient selection is guided by clinical parameters as well as by biomarker concentrations, by measuring circulating bio-ADM (sphingotest bio-ADM, sphingotec GmbH, Hennigsdorf, Germany). 25 Based on preclinical studies, two dosages of adrecizumab will be investigated (2 and 4 mg/kg body weight), in addition to a placebo control arm.
Patient selection A total of 300 adult patients with early septic shock and elevated bio-ADM concentration will be randomised. Early septic shock is defined as sepsis with hypotension (mean arterial pressure<65 mm Hg) refractory to fluid Open access resuscitation and requiring vasopressor therapy. 4 Patients with a measurement of circulating bio-ADM >70 pg/mL will be eligible to be randomised. The cut-off point for bio-ADM of 70 pg/mL was selected based on the specific needs and purpose of this study. Per patient data available for this evaluation included data from the Albumin Replacement in Patients with Severe Sepsis or Septic Shock (ALBIOS), Frog-ICU and AdrenOSS-1 studies, to name the largest and most relevant, as well as data from healthy normal individuals. Specific needs to be met for the study were that patients with normal bio-ADM, as well as low severity and low expected mortality were to be excluded, to maximise the observable treatment effect, while keeping the eligible population as large as possible.
Withdrawal Participation is strictly voluntary and a patient or their legal representative may withdraw the patient from the study at any time without providing an explanation. This will not affect his/her right for future medical care. If a patient would withdraw from the study, the date, circumstances and any reason provided will be documented on the withdrawal page of the eCRF. No study-specific data or patient material will be collected after withdrawal of consent. No data obtained after withdrawal of consent will be recorded on eCRFs, unless the patient consents to the use thereof. For safety analysis, the patient's outcome status (dead or alive) at day 90 will be collected. For the main efficacy analysis, these patients will be excluded. In order to rule out that patient withdrawal is linked to treatment, a sensitivity analysis will be conducted assigning missing end point data with the worst possible value (ie, worst possible value for patients in the treatment group, the best possible value for patients in the control group).
Behavioral testing: open field test (OF) We evaluated the drug (S 47445 or fluoxetine) effects on the OB-induced hyperactivity (to assess antidepressant-like effects) and central ambulation (to assess anxiolytic-like effects)  (Linge et al. , 2016). The open field test was performed during the light phase (between 8 and 11 a. m. ). Animals were transported to the experimental room 1 h before the start of the experiment to acclimatize, and 24 h after drug administration. The open field apparatus was a brightly lit (350 lx) white wooden box (50 cm × 50 cm × 30 cm) with white floor and bright walls. Mice were placed in the center of the apparatus for 5 min, and behavior was videotracked using a computerized system (Any-maze Video-Tracking software, Stoelting Co. , U. S. A. ). Total, peripheral and central distances travelled were measured.
(USA), overnight. After extensive washings in TBS-T (TBS, 0. 05% Tween 20) membranes were incubated with horseradish peroxidase conjugated secondary antibodies. Specific signal was detected using ECL Advance kit (GE Healthcare Europe GmbH, Munich, Germany). Blots quantitation was performed by densitometric analysis using Scion Image Software. The densitometry values were normalized with respect to β-tubulin. Those values were used to calculate p-mTOR/mTOR and p-4EBP1/4EBP1 ratios.
ACKNOWLEDGEMENTS This research was supported by the  Institut de Recherches Internationales Servier , the  Spanish Ministry of Economy and Competitiveness  ( SAF2015-67457-R ),  Instituto de Salud Carlos III  ( FIS Grant   PI13-00038 ) co-funded by the  European Regional Development Fund  ('A way to build Europe') and  Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM). We thank the technical assistance of  Dr. Raquel Linge ,  Beatriz Romero ,  Raquel Gutierrez-Lanza  and  Alicia Martín. The authors would like to thank  Professor Elsa Valdizán  for her contribution.
Structure and division of the mouse brain model The model is based on the Allen Brain Atlas (ABA), which compiles tracer injections, selectively sampling mice brain volumes, to map axonal projections of different areas within the adult mouse brain (see Figure  1 ). The database of the Allen Brain Atlas was spatially sampled with a resolution of 50 µm (voxel of 50 (µm) 3 isotopically sample the volume). In this way, the model distinguishes between 512 distinct brain areas. The smooth surface of the isocortex was reconstructed from the ABA, approximated by a regular mesh of 27,554 triangles with 41,524 edges (88 µm is the length of the shortest edge, 190 µm is the longest edge, with a mean edge length of 125 µm) between 13,972 vertices (Figure  11 ), and spatially divided into 84 cortical areas given by the ABA.
e. , whisker, auditory, forelimb, hindlimb, and visual). These locations were used to find a projection plane (size given by the camera sensor used for the VSD imaging) in the model that best corresponds to the VSD imaging data (see Figure  15 ). This mapping provides then a direct link of the local PSP in the model to the measured VSD images. The isocortical areas, captured by the VSD imaging setup (see, for more details,  Mohajerani et al. , 2013) , are listed in Table  6. Simulated and measured activity can thus be compared on the imaging level as well as by the region mapping.
DISCUSSION Brain network dynamics can be systematically explored only in silico. To explore the mouse brain dynamics in silico, we built a high-resolution whole mouse brain model. The model structure is based on the database Allen Brain Atlas (ABA) comprising tracer studies. We investigated the network behavior by assuming simple oscillatory but canonical dynamics at each brain region, that is, a network node. Each region had the same local dynamics, only differentiated by the ABA connectome from one to the other. We simulated the whole-brain mouse model on a computer using the neuroinformatics platform The Virtual Brain (TVB). To test whether the mouse brain activity can be exclusively inferred from the underlying connection topology, we performed graph theoretic analysis of the model structure.
Modeling results The structure of the model (Figure  1 ) based on the database of the Allen Brain Atlas comprising tracer studies was coregistered with the anatomy of the mouse brain (see  Oh et al. , 2014). We spatially sampled the brain volume given by the ABA and obtained a network model composed of 512 distinct brain areas. The model incorporates the smooth surface of the isocortex that we reconstructed from the ABA using a regular mesh of 27,554 triangles with 41,524 edges between 13,972 vertices (Figure  11 ) and the spatial extent of the 84 cortical areas given by the ABA. The 512 distinct brain areas contain the 84 isocortical areas (42 per hemisphere) and 428 non-isocortex areas (see Table  1  for the division, Table  2  and Table 3  for a complete list of area names). These 428 sub-isocortical areas are lumped in the model to a point in physical space (i.