dataesr/scientific-paragraphs-categorization huggingface dataset:
Fold change values are associated with an adjusted value of statistical significance (p adj ) where p<0. 01 is considered significant. In all, 235 genes were significantly upregulated in vivo and 264 genes were downregulated in vivo. These values represent 17% upregulated genes and 20% downregulated genes, thus demonstrating substantial transcriptional differences between in vitro and in vivo Rickettsia rickettsii. Validation of RNAseq by quantitative RT-PCR 16 genes were chosen for individual analysis in order to validate the RNAseq data by an independent experimental method. To this aim, both RNA and gDNA were re-isolated from the RNAseq source material. The isolated RNA samples were subjected to DNAase treatment, reverse transcription, and quantitative PCR (qRT-PCR) to determine cDNA concentration for each of the 16 genes.
In order to control for rickettsial nucleotide concentration in the PCR reaction, we utilized gDNA copies present in the biological sample. The concentration of R. rickettsii sca1 copies per murine actin gDNA was determined in each sample, with a sca1/actin ratio of 3. 27 for the in vivo infected liver sample and 78. 32 in the in vitro sample. By adding equal amounts of cDNA and dividing the calculated cDNA concentration by the gDNA ratio, we are able to properly control for changes to the quantity of input Rickettsia RNA. This data transformation allows for accurate determination of the fold change in expression of each of the tested genes despite the contaminating host RNA. The qRT-PCR data for the 16 analyzed genes was compared to the fold change values obtained by RNAseq (Fig  1 ). Logically, if the two data acquisition mechanisms produce consistent results, then the two data sets should have a strong linear correlation.
Discussion Herein, we describe the use of RNAseq technology to ascertain quantity of and changes to R. rickettsii RNA content in vivo compared to in vitro. The in vitro RNA samples are prepared from R. rickettsii in routine Vero cell culture at the point of maximal bacterial burden. The transcriptome of those bacterial samples is compared to in vivo R. rickettsii derived from infected murine liver at the point of maximum morbidity. As such, comparison of these samples establishes adjustments made by the bacterium in response to the challenges of mammalian infection. The RNAseq data was validated by qRT-PCR to establish the validity of the The high bacterial load in the liver in this mouse model of R. rickettsii infection is different than occurs in the well-known guinea pig model of infection.
Acknowledgments These studies were aided by the  Gene Lab unit of the Center for Experimental Infectious Disease and Research at the Louisiana State University School of Veterinary Medicine. We would like to particularly acknowledge the efforts of  Vladimir Chouljenko  and  John Caskey  in completion of this study. The authors would like to thank  Pedro Curto ,  Isaura Simões ,  Abigail Fish , and  Daniel Garza  for helpful suggestions in completion of this study and preparation of this manuscript.
ABSTRACT We present a new catalogue of solar energetic particle events near the Earth, covering solar cycle 23 and the majority of solar cycle 24 , based on the 55-80 MeV proton intensity data gathered by the SOHO/ERNE experiment. In addition to ERNE proton and heavy ion observations, data from the ACE/EPAM (near-relativistic electrons), SOHO/EPHIN (relativistic electrons), SOHO/LASCO (coronal mass ejections, CMEs), and GOES soft X-ray experiments are also considered and the associations between the particle and CME/X-ray events deduced to obtain a better understanding of each event. A total of 176 SEP events have been identified as having occurred during the time period of interest; their onset and solar release times have been estimated using both velocity dispersion analysis (VDA) and time-shifting analysis (TSA) for protons, as well as TSA for near-relativistic electrons.
SOHO/ERNE proton data and event selection The ERNE experiment  (Torsti et al. 1995)  aboard the SOHO spacecraft served as the primary instrument in this study. ERNE consists of two particle telescopes, the Low-Energy Detector (LED) and the High-Energy Detector (HED), which together are designed to cover the nominal energy range of some 1 MeV/nucleon to a few hundred MeV/nucleon for ions. For protons and helium ions, the upper limit of the energy range is about 140 MeV/nucleon. For the reasons explained in the previous chapter, the proton energy channel of 54. 8-80. 3 MeV (average energy 67. 7 MeV) was chosen as the principal channel to be investigated. To identify the SEP events that had occurred during the time of interest, we scanned visually through SOHO/ERNE intensity data collected during the period between May 1996 and December 2016.
Onset, solar release, and event end time determination The proton event onset times as observed by SOHO/ERNE were determined using the so-called Poisson-CUSUM method. This essentially measures the statistical quality of a process to decide whether or not the process is under control and determines the moment of time of a failure occurring. Here, the pre-event background level proton flux is analogous to a controlled process, while a flux Table  1. Major (longer than ∼ 18 h) continuous ERNE data gaps. All times are UT. 28-31-May-1996  28-29-Jul-2001  26-27-Sep-2010  14-15-Oct-2013  03-Jun-1996  10-17-Aug-2001  10-15-Dec-2010  29-Oct-04-Dec-2013 e  15-16-Feb-1997  01-03-Jan-2002  09-13-Jan-2011  29-31-Jan-2014  25-Feb-04-Mar-1997  24-25-Jan-2002  13-14-Jan-2011  21-Mar-2014  25-28-Oct-1997  05-12-Feb-2002  07-Apr-2011  21-Sep-2014  19-21-Nov-1997  24-May-2002  17-Jul-2011  02-03-Nov-2014  27-Nov-1997  01-02-Jul-2003  21-Jul-2011  17-19-Dec-2014  11-12-Dec-1997  14-15-Jan-2003 30-Nov-2011-05-Jan-2012 b 09-15-Jan-2015 04-05-  Feb-1998 28-Feb-11-Mar-2003 22-24-Jan-2012 24-26-Jan-2015 25-28-Feb-1998 05-Jul-2003 25-27-Jan-2012  12-14-Feb-2015 a 24-Jun-09-Oct-1998 09-10-Jul-2003 28-Jan-10-Feb-2012 c 14-Feb-2015 14-21-  Nov-1998 22-24-Oct-2003 15-16-Feb-2012 23-24-Mar-2015 01-03-Dec-1998 19-22-Jan-2004 04-May-2012 05-Jun-2015 21-Dec-1998 -08-Feb-1999 26-Mar-2004  07-May-2012  (a) Some data are available during this period.
1998 ; http: //www. srl. caltech. edu/ACE/ASC/level2/lvl2DATA_SWEPAM. html), with Wind/SWE data  (Ogilvie et al. 1995 ; http://omniweb. gsfc. nasa. gov/ftpbrowser/wind_swe_2m. html) substituted for the events for which the former were not available. In each case the data were averaged over a 12-hour period, centered on t onset for 54. 8-80. 3 MeV protons observed by ERNE; in cases where the precise t onset for protons was unknown but known for electrons, the UT calendar day (24 hours) during which the onset had most likely occurred was used to obtain L for electron TSA. The Earth-Sun and Earth-spacecraft distances were averaged over the period of interest in the same manner. In addition to proton data, we examined electron intensity data recorded by both ACE/EPAM (near-relativistic electrons) and SOHO/EPHIN (relativistic electrons).
These were analysed for onset times, and ACE/EPAM data additionally for maximum intensities during the events as well as particle release times, so as to form a more complete picture of each event than would be possible by relying on proton data alone. By default, the ACE/EPAM data  (Gold et al. 1998 ) used in our analysis were sectored one-minute intensities observed by the LEFS60 3  (Low-Energy Foil Spectrometer) telescope. These data were checked for ion contamination by comparing them visually with proton intensities recorded by the LEMS120 (Low-Energy Magnetic Spectrometer) telescope, as well as with electron intensities recorded by DE30 (Deflected Electrons). If any indications of possible ion contamination were detected in the LEFS60 intensity data, DE30 data were used instead. While ion contamination occasionally presents an issue for electron data recorded by LEFS60, it has the advantage of having a larger geometric factor than DE30 (∼ 0.
40 cm 2 sr for electrons for the former, compared to ∼ 0. 14 cm 2 sr for the latter) and was for this reason preferred in our study. A similar electron intensity profile comparison to determine possible ion contamination is described in  Malandraki et al. (2000). The authors performed their comparison on data recorded during an SEP event by the Ulysses/HI-SCALE instrument which is virtually identical to ACE/EPAM (the latter being the flight spare of Ulysses/HI-SCALE). The electron event onset times for ACE/EPAM were determined by first estimating the yearly background intensity (I bg ), calculating the sliding time-average intensity I av (t) over 60 minutes, and then comparing I av (t) and the corresponding standard deviation to data points following the time window by another 60 minutes. When five consecutive data points all showed an intensity equalling or exceeding I av (t) + nσ, where n was a user-defined constant (with the default value of 2.
The principal ACE/EPAM energy channel used for determining the onsets was 0. 18-0. 31 MeV. However, in five cases (events 1, 10, 41, 118, and 141) it was deemed necessary to resort to the 0. 10-0. 18 MeV energy channel so as to obtain a clear result, due to an elevated pre-event background or weak enhancement of the intensity in the higher energy channel. The energy ranges correspond to mean electron energies of 0. 23 MeV and 0. 13 MeV and thus mean speeds of 0. 73 c and 0. 61 c, respectively. These speeds are so high, and the number of available energy channels (four) so small, that attempting to perform VDA for ACE/EPAM electron data was not expected to produce reliable results in most cases. Instead, the onset times were determined for each event and, after discarding cases where no reasonable result for t onset could be obtained, only TSA was performed.
Near-relativistic electron event information derived from ACE/EPAM observations is complemented by event onset times determined from SOHO/EPHIN electron data  (Müller-Mellin et al. 1995). The energy channel of interest was 0. 7-3. 0 MeV. The onset was defined in a similar, but slightly simpler, manner as for ACE/EPAM data: the average intensity over a specified time window I av and the corresponding standard deviation σ multiplied by a user-defined constant n were compared to immediately following data points, and the time stamp of the first data point to exceed the intensity value of I av + nσ (where in this case n = 4. 0) was taken as the time of onset. No detrending or release time analysis was performed for these electron observations, but they are included in this article to continue the analysis of the datasets used in  Vainio et al.
(2013). The durations of the SEP events were estimated according to the basic criteria explained in 2. 1 in the following manner. The preliminary event end times were derived by locating the time point where the proton intensity in the 12. 6-13. 8 MeV energy channel first fell below the pre-defined threshold value (2. 0 × the pre-event average background intensity or the quiet time background intensity, if the former was substantially elevated) after the 55-80 MeV proton event onset. The period between the onset and the preliminary event end was then scanned visually for data gaps and new low-energy SEP events not visible in high energies. If any were found, the event ending time was shifted to the nearest noon or midnight UT before the next low-energy event or to the beginning of an extensive-i.
Ion fluences and iron-to-oxygen ratios Fluences (i. e. , differential particle intensities integrated over a given range of energy and time, expressed here in cm -2 sr -1 ) of energetic protons and oxygen ions, as well as iron/oxygen ratios, were calculated for each event using ERNE data. For protons, the energy range of interest was from ∼ 10 MeV to 140  MeV (prior to 19 April 2000)  or 131  MeV (after 19 April 2000) ; the two different upper limits follow from a modification to the ERNE onboard software with a data format change on the date given above. As the bulk of the ion fluence is expected to occur at low energies, however, this difference is unlikely to have a large impact on the results. The estimated quiet-time background was first subtracted from the intensities of each energy channel.
Soft X-ray and CME data The tabulated information regarding X-ray flare events is based on GOES satellite data made available by the United States National Oceanic and Atmospheric Administration (NOAA; http://www. ngdc. noaa. gov/stp/space-weather/solar-data/solar-features/ solar-flares), with the flare/SEP event association deduced by us. The electromagnetic (EM) wavelength band of interest was 0. 1-0. 8 nm, i. e. soft X-rays. However, only flares with NOAA/GOES magnitude classification of C1. 0 or greater (peak flux at least 10 -6 W/m 2 ) were taken into consideration. Flare onset, classification, and location were in the majority of cases provided directly by NOAA listings, and the time derivative maximum of the soft X-ray flux was calculated based on the flux data smoothed with five-minute sliding average for use in the particle injection time estimation.
If the listing included a CME with an estimated solar surface departure time differing from the radio and flare activity by less than ∼ one hour, it was analysed further and then selected for our catalogue, if its association with the SEP event appeared reasonably certain in light of other evidence (see 2. 5 for an example). We list the first detection of the CME as observed on the SOHO/LASCO C2 coronagraph, with the time figure rounded to the nearest minute. In a few cases, the CME was not observed on C2; for these events, the first observation is recorded for the C3 (see notes for Table  4 ). For a detailed introduction to the CME Catalog and discussion, see  Gopalswamy et al. (2009). While radio frequency observations are not included in the tables presented in this article, spectral plots of Wind/WAVES data 6  were scanned visually during periods of SEP, CME, and flare X-ray activity to find out whether or not type III microwave bursts were detected close in time to both the onset of the candidate flare and the surface lift-off of the candidate CME.
A linear fit to observation data points presented in the SOHO LASCO CME Catalog gives the speed of the CME as 1556 km/s and the departure time from the solar surface as 11:30. This is corroborated by a visual scan of Wind/WAVES data, which indicates considerable type III radio burst activity beginning at circa 11:52. NOAA listings show that during a few hours within noon of 6 November 1997, two soft Xray flares with NOAA classification greater than C1. 0 were detected by GOES: a C4. 7 class flare, beginning at 11:31 and ending at 11:44; and an X9. 4 class flare, beginning at 11:49 and ending at 12:01. The location of the X9. 4 class flare is given in the listing as 18S 63W, and our analysis indicates the maximum of the time derivative of the soft X-ray flux as having occurred at 11:53. The larger and later of the two flares coincides with the estimated departure from the solar surface of the CME, as well as the derived particle release times for both 55-80 MeV protons and 0.
This leaves 128 events for which at least some information of the associated GOES flare is available and the flare identification is relatively secure. Thirteen of these flares certainly or very likely occurred at or immediately behind the solar limb; thus, full flare information (time of the maximum of the intensity time derivative, classification, location) is listed for 115 events  (72 during 1996-2008, 43 events during 2009-2016). Independent longitude estimation was not attempted for the farside flares. The observation that SEP events and CMEs are associated and that the peak intensities of the events are correlated with CME speed is well established (see e. g. Kahler et al. 1984 , Kahler 2001). It is therefore unsurprising that in our data set, virtually every SEP event that extended to proton energies above 55 MeV was accompanied by an identifiable CME.
In addition to these two outstanding cases, SOHO/LASCO data are missing for five events, and there are otherwise insufficient data to make a positive determination as to the particle eventassociated CME in three cases. All the other 166 events exhibit unambiguous CME activity. Of these,  136 (91 in 1996-2008, 45 in 2009-2016)  were also known to be associated with a GOES flare on the visible solar disk or over the western solar limb (the cases of missing X-ray intensity data are excluded from these figures). Estimates for both the speed and apparent angular size are available for all CMEs listed in our catalogue, aside from seven in 1996-2008, for which the SOHO LASCO Catalog only reports a lower limit for the size, in addition to the estimated speed.
Unphysical results may be caused by one or a few onset times given by the algorithm, which are clearly erroneous. Removing these data points from the VDA may give physically more significant results, but of course also makes these particular results more subjective in the sense that one has to decide which data points to remove from the analysis. The cases with no VDA result were omitted from consideration. Additionally, there were nine cases of very long (> 5 AU) and seven cases of very short (< 1 AU) apparent path lengths among the 161 events. In four of the former and two of the latter events, at least three energy channels were discarded from the VDA, and in three cases the proton intensity measured by ERNE increased very slowly at event onset. However, it is noteworthy that redoing the VDA with a more critical view on the goodness of the data points has decreased the number of the unphysically short apparent path lengths: in  Vainio et al.
(2013) , a path length of less than 1 AU is reported to have resulted in eight of 111 events. The distributions of apparent path lengths are shown in Figure  2. When all events are considered as one set, the distribution is somewhat reminiscent of a Gaussian one with its peak at ∼ 1. 6 AU, but its symmetry is broken by a second local maximum at ∼ 2. 2 AU and a third, somewhat weaker one at ∼ 2. 8 AU, as well as an apparent gap at 3. 0 AU. The 1. 6 AU peak is close to typical calculated values of the Parker spiral length. The corresponding 0. 2 AU-wide bins contain 19, 19, and 13 events, respectively. Apart from the first one, these maxima may result from the poor statistics and they do not necessarily have any physical significance. The 1996-2008 (solar cycle 23) and 2009-2016 (solar cycle 24) datasets, considered separately, present broadly similar distributions that would nevertheless seem to exhibit some difference in details.
For the former, the first maximum occurs at 1. 4 AU, and the third maximum at 2. 8 AU is comparatively weak; the greatest number of events (17) falls into the 2. 2 AU bin. In contrast, for the 2008-2016 events, the 1. 6 AU bin dominates (9 events), and there is no clear maximum at 2. 2 AU, while one possibly appears at 2. 8 AU (and perhaps another at 3. 2 AU). However, this set suffers from particularly poor statistics, and these features are unlikely to be of actual significance. For the same reason, the observations regarding the solar cycle 23 dataset must be considered with due caution. The average apparent path lengths (and their standard errors of the mean) are 2. 47±0. 20 AU for the 1996-2008 events, 2. 60±0. 22 AU for the 2009-2016 events, and 2. 51±0. 15 AU for the entire data set.
Taking l = L, we can express the effective value for µ as µ eff = μ = L/s. Figure  4  represents the distribution of L/s. Omitting the cases for which L/s > 1 as unphysical, the mean and standard deviation, respectively, are for the datasets as follows: 0. 54 and 0. 20 (all events), 0. 55 and 0. 20 (the 1996-2008 events), and 0. 52 and 0. 20 (the 2009-2016 events). This result is in good agreement with the results given in  Vainio et al. (2013). It also underscores the fact, earlier found in simulation studies and pointed out by e. g. Lintunen and Vainio (2004)  and  Sáiz et al. (2005) , that even the earliest-arriving particles cannot be regarded as moving directly along the magnetic field line, challenging one of the basic assumptions of VDA. Overall, the mean and standard deviation values as such do not reveal any remarkable changes between the solar cycles.
To investigate quantitatively the level of correlation between the longitudinal distance and the time difference, a regression line was fitted to both solar cycle 23 and 24 data sets. When only the core population, shown in Figure  8 , is considered in the fit, the results are similar for both cycles. While the statistical significance of the fit is not particularly great in either of these instances, and a lot of scatter is present in the data, the slopes and the intercepts of the lines are nevertheless sensible in that both are greater than zero and the latter lie in the range of 15-20 minutes. This indicates that in a very well connected event, the maximum energy release in the flare/CME, as estimated from the X-ray intensity time derivative maximum 9  , would tend to occur some twenty minutes or less before the electron release, as estimated from TSA.
However, it is noteworthy that the available evidence points to a clear decrease of SEP events with hard spectrum during solar cycle 24, as compared to cycle 23 (see, e. g. ,  Mewaldt et al. 2015  for an in-depth discussion). In our data, the seven-year period from 1996 to 2003 contains 92 proton events in the 55-80 MeV energy range, while only 62 are recorded for 2009-2016. (Both of these figures probably somewhat underestimate the respective numbers of actual SEP events, owing to gaps in the ERNE data. ) Furthermore, only one ground level enhancement (GLE) event has so far occurred during solar cycle 24, whereas there were 13 in the first eight years  (1996) (1997) (1998) (1999) (2000) (2001) (2002) (2003)  of solar cycle 23 (as per the GLE database, http://gle. oulu. fi/); the corresponding numbers of sub-GLE events 10  for these time periods are 11 and 10  (Vainio et al.
Conclusions and outlook Studying SOHO/ERNE data, we identified 176 55-80 MeV proton events that occurred during 1996-2016. We determined their onset times at 1 AU, their maximum intensities, proton and oxygen fluences, and Fe/O ratio, and performed VDA and TSA for the events. The associated energetic electron events were also identified from ACE/EPAM data and their onsets determined. TSA was then performed for the electron events. Lastly, we attempted to identify X-ray flares and CMEs corresponding to the particle events, obtaining estimates for particle solar release times from the maxima of the time derivative of the soft X-ray intensity. This accumulated information is presented in the form of an event catalogue, in two parts (Tables  3  and 4 ). In all but a few cases, the identification and subsequent analysis of the electron event accompanying the proton event was successful.
Acknowledgements. The research described in this paper was supported by  ESA  contract  4000113187/15/D/MRP. We would like to acknowledge and express our gratitude to the organizations and teams responsible for maintaining the data sources used in this article ( SEPServer, SOHO LASCO CME Catalog, SolarSoft Latest Events Archive, NOAA/Solar-Terrestrial Physics  at the  National Centers for Environmental Information , Coordinated Data Analysis Web, the  ACE Science Center , and the GLE database). SOHO LASCO CME Catalog: this CME catalog is generated and maintained at the CDAW Data Center by  NASA  and  The Catholic University of America  in cooperation with the  Naval Research Laboratory. SOHO is a project of international cooperation between  ESA  and  NASA. O. R. wishes to thank the  Vilho, Yrjö  and  Kalle Väisälä foundation  for financial support.