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High-precision pulsar timing observations are limited in their accuracy by the jitter noise that appears in the arrival time of pulses. Therefore, it is important to systematically characterise the amplitude of the jitter noise and its variation with frequency. In this paper, we provide jitter measurements from low-frequency wideband observations of PSR J0437$-$4715 using data obtained as part of the Indian Pulsar Timing Array experiment. We were able to detect jitter in both the 300–500 MHz and 1 260–1 460 MHz observations of the upgraded Giant Metrewave Radio Telescope (uGMRT). The former is the first jitter measurement for this pulsar below 700 MHz, and the latter is in good agreement with results from previous studies. In addition, at 300–500 MHz, we investigated the frequency dependence of the jitter by calculating the jitter for each sub-banded arrival time of pulses. We found that the jitter amplitude increases with frequency. This trend is opposite as compared to previous studies, indicating that there is a turnover at intermediate frequencies. It will be possible to investigate this in more detail with uGMRT observations at 550–750 MHz and future high-sensitive wideband observations from next generation telescopes, such as the Square Kilometre Array. We also explored the effect of jitter on the high precision dispersion measure (DM) measurements derived from short duration observations. We find that even though the DM precision will be better at lower frequencies due to the smaller amplitude of jitter noise, it will limit the DM precision for high signal-to-noise observations, which are of short durations. This limitation can be overcome by integrating for a long enough duration optimised for a given pulsar.
A novel excretory–secretory (ES) protein of Trichinella pseudospiralis was produced. A cDNA library was constructed from mRNA of muscle larvae at 30 days post infection (p.i.) and immunoscreened with the antibody against ES products. A clone, designated Tp22-3, contained a cDNA transcript of 815 bp in length with a single open reading frame which encoded 244-amino acids (28407 Da in the estimated molecular mass). A database search revealed that no sequences had a homology to this predicted protein. The recombinant protein was produced in an Escherichia coli expression system. Stage specific expression of this protein was suggested from the following experiments. An antibody against the recombinant protein could stain proteins migrating at about 28 kDa (which is the expected size from the sequence) on Western blotting of crude extracts or ES products from 30 days p.i. muscle larvae, but failed to stain any proteins in crude extracts from newborn larvae or 15 days p.i. muscle larvae. The antibody reacted to the stichocytes of larvae at 30 days p.i., but did not react to 15 days p.i. muscle larvae. The production of an mRNA transcript for Tp22-3 gene was restricted largely to the 30 days p.i. muscle larvae and adult worms.
Recombinant protein was produced from the cDNA library of Trichinella pseudospiralis, which seemed to form part of the excretory–secretory (ES) products. The library was constructed from cDNA of muscle larvae at 1 month post-infection, and immunoscreened with antibody against T. pseudospiralis ES products. A clone, designated Tp21-3, contained a cDNA transcript of 657 bp in length with a single open reading frame, which encoded 172 amino acids (19617 Da in the estimated molecular mass). The predicted amino acid sequence of clone Tp21-3 had a similarity of 76% to that of clone ORF 17.20 (GenBank under accession number U88239) from T. spiralis. The recombinant fusion proteins encoded by clone Tp21-3 were produced in an Escherichia coli expression system and affinity purified. On Western blotting analysis, Tp21-3 recombinant proteins migrated at 40 kDa and reacted to antibody against T. pseudospiralis ES products and T. pseudospiralis-infected sera. Sera were developed against Tp 21-3 recombinant proteins, which reacted to a single band migrating at 21 kDa in crude worm extract and ES products from T. pseudospiralis on Western blotting analysis, and reacted with stichocytes of T. pseudospiralis on immunohistochemical staining.
The nurse cell in the cyst of Trichinella spiralis comprises at least two kinds of cytoplasm, derived from muscle or satellite cells, as indicated by the pattern of staining using regular dye (haematoxylin and eosin, or toluidine blue), alkaline phosphatase (ALP) expression, acid phosphatase (ACP) expression and immunostaining with an anti-intermediate filament protein (desmin or keratin). Muscle cells undergo basophilic changes following a T. spiralis infection and transform to the nurse cells, accompanied by an increase in ACP activity and the disappearance of desmin. Satellite cells are activated, transformed and joined to the nurse cells but remain eosinophilic. The eosinophilic cytoplasm is accompanied by an increase in desmin and ALP expression but not an increase in ACP activity. Differences in the staining results for ALP or ACP suggest that the two kinds of cytoplasm have different functions. Trichinella pseudospiralis infection results in an increase of ACP activity at a later stage than T. spiralis. There is also a difference in the location pattern of ACP in the cyst of T. spiralis compared with T. pseudospiralis. In T. spiralis, ACP is diffused within the cell, but in T. pseudospiralis, ACP distribution is spotty corresponding to the location of the nucleus. Trichinella pseudospiralis infection is accompanied by a slight increase in ALP activity. Activated satellite cells following a T. pseudospiralis infection exhibit an increase in desmin expression. The present study therefore reveals that nurse cell cytoplasm differs between the two Trichinella species and between the two origins of cytoplasm in the cyst of T. spiralis.
A clone, designated as TsTM, was selected from the cDNA library of newborn larvae (NBL) of Trichinella spiralis through immunoscreening against infected sera. The clone contained a cDNA transcript of 855 bp in length with a single open reading frame, which encoded 285-amino acids (33 kDa in the estimated molecular weight). A sequence analysis revealed that the clone TsTM encoded the full-length of tropomyosin gene. The phylogenetic analysis of the tropomyosin gene was in good agreement with the classical taxonomical position of T. spiralis. The fusion proteins encoded by the clone TsTM were produced in an Escherichia coli expression system and affinity purified, and the antibody was raised against the protein for the following studies. The antibody against the fusion protein positively bound to the hypodermal muscle layer in immunolocalization analysis, and the 35 kDa band in crude extracts of muscle larvae but not in excretory and secretory (ES) products on Western blots. The antigenicity of the clone TsTM was recognized by host mice but exhibited little species specificity.
We present the pulse arrival times and high-precision dispersion measure estimates for 14 millisecond pulsars observed simultaneously in the 300$-$500 MHz and 1260$-$1460 MHz frequency bands using the upgraded Giant Metrewave Radio Telescope. The data spans over a baseline of 3.5 years (2018-2021), and is the first official data release made available by the Indian Pulsar Timing Array collaboration. This data release presents a unique opportunity for investigating the interstellar medium effects at low radio frequencies and their impact on the timing precision of pulsar timing array experiments. In addition to the dispersion measure time series and pulse arrival times obtained using both narrowband and wideband timing techniques, we also present the dispersion measure structure function analysis for selected pulsars. Our ongoing investigations regarding the frequency dependence of dispersion measures have been discussed. Based on the preliminary analysis for five millisecond pulsars, we do not find any conclusive evidence of chromaticity in dispersion measures. Data from regular simultaneous two-frequency observations are presented for the first time in this work. This distinctive feature leads us to the highest precision dispersion measure estimates obtained so far for a subset of our sample. Simultaneous multi-band upgraded Giant Metrewave Radio Telescope observations in 300$-$500 MHz and 1260$-$1460 MHz are crucial for high-precision dispersion measure estimation and for the prospect of expanding the overall frequency coverage upon the combination of data from the various Pulsar Timing Array consortia in the near future. Parts of the data presented in this work are expected to be incorporated into the upcoming third data release of the International Pulsar Timing Array.
First responders to disasters are at risk of developing post-traumatic stress disorder (PTSD). The trajectories of post-traumatic stress symptom severity differ among individuals, even if they are exposed to similar events. These trajectories have not yet been reported in non-Western first responders.
Objectives
We aimed to explore post-traumatic stress symptom severity trajectories and their risk factors in first responders to the 2011 Great East Japan Earthquake (GEJE)— a historically large earthquake that resulted in a tsunami and a nuclear disaster.
Methods
56 388 Japan Ground Self-Defense Force (JGSDF) personnel dispatched to the GEJE were enrolled in this seven-year longitudinal cohort study. PTSD symptom severity was measured using the Impact of Event Scale-Revised (IES-R). Trajectories were identified using latent growth mixture models (LGMM). Nine potential risk factors for the symptom severity trajectories were analyzed using multinomial logistic regression.
Results
Five symptom severity trajectories were identified: “resilient” (54.7%), “recovery” (24.5%), “incomplete recovery” (10.7%), “late-onset” (5.7%), and “chronic” (4.3%). The main risk factors for the four non-resilient trajectories were older age, personal disaster experiences, and working conditions. These working conditions included duties involving body recovery or radiation exposure risk, longer deployment length, later or no post-deployment leave, and longer post-deployment overtime.
Conclusions
The majority of first responders to GEJE were resilient and developed few or no PTSD symptoms. A substantial minority experienced late-onset and chronic symptom severity trajectories. The identified risk factors can inform policies for prevention, early detection, and intervention in individuals at risk of developing symptomatic trajectories.
With an annual growth in travel demand of about 5% globally, managing the environmental impact is a challenge. In 2019, the International Civil Aviation Organisation (ICAO) issued emission reduction targets, including well-to-wake greenhouse gas (GHG) emissions reduced at least 50% from 2005 levels by 2050. This discusses several technologies from an aircraft design perspective that can contribute to achieving these targets. One thing is certain: aircraft will look different in the future. The Transonic Truss-Braced Wing and Flying V configurations are promising significant efficiency improvements over conventional configurations. Electric propulsion, in various architectures, is becoming a feasible option for general aviation and commuter aircraft. It will be a growing field of aviation with zero-emissions flight and opportunities for special missions. Lastly, this paper discusses methods and design processes that include all relevant disciplines to ensure that the aircraft is optimised as a complete system. While empirical methods are essential for initial design, Multidisciplinary Design Optimisation (MDO) incorporates models and simulations integrated in an optimisation environment to capture critical trade-offs. Concurrent design places domain experts in one site to facilitate collaboration, interaction, and joint decision-making, and to ensure all disciplines are equally considered. It is supported by a Collaborative Design Facility (CDF), an information technology facility with connected hardware and software tools for design analysis.
In the present study, compressible low-Reynolds-number flow past a stationary isolated sphere was investigated by direct numerical simulations of the Navier–Stokes equations using a body-fitted grid with high-order schemes. The Reynolds number based on free-stream quantities and the diameter of the sphere was set to be between 250 and 1000, and the free-stream Mach number was set to be between 0.3 and 2.0. As a result, it was clarified that the wake of the sphere is significantly stabilized as the Mach number increases, particularly at the Mach number greater than or equal to 0.95, but turbulent kinetic energy at the higher Mach numbers conditions is higher than that at the lower Mach numbers conditions of similar flow regimes. A rapid extension of the length of the recirculation region was observed under the transitional condition between the steady and unsteady flows. The drag coefficient increases as the Mach number increases mainly in the transonic regime and its increment is almost due to the increment in the pressure component. In addition, the increment in the drag coefficient is approximately a function of the Mach number and independent of the Reynolds number in the continuum regime. Moreover, the effect of the Mach and Reynolds numbers on the flow properties such as the drag coefficient and flow regime can approximately be characterized by the position of the separation point.
Recent research on Flight-deck Interval Management (FIM), a modern technology for increasing safety and improving airspace and runway utilisation through self-spacing, has led to the development of a new rule-based logic for FIM, namely Interval Management – Speed Planning (IM-SP). In an initial benchmark study, IM-SP showed good spacing performance with a significant reduction in speed commands, a major area of concern with previous FIM logics, resulting in a lower burden on the flight crew during FIM operation. Nevertheless, there remains scope for improvement in other aspects, such as fuel burn. In this study, the internal cost function of IM-SP is further analysed and optimised using speed-constrained multi-objective particle swarm optimisation to improve the performance of IM-SP under the multiple objectives of FIM. The optimisation renders new settings that address the problem areas, improve the speed commands and enhance the overall quality of IM-SP. Two distinctive solutions, viz. a spacing performance optimised setting and a fuel burn optimised setting, are further analysed and discussed, and directions for follow-up research are explored.
The authors evaluated cerebral blood flow response in schizophrenia patients during face perception to test the hypothesis of diminished limbic activation related to emotional relevance of facial stimuli.
Method
Thirteen patients with schizophrenia and 17 comparison subjects viewed facial displays of happiness, sadness, surprise, anger, fear, and disgust as well as neutral faces using the Japanese and Caucasian Facial Expressions of Emotion and Neutral Faces (Matsumoto and Ekman, 1988). Functional magnetic resonance imaging was used to measure blood-oxygen-level-dependent signal changes as the subjects alternated between tasks of discriminating sex with an interleaved reference condition.
Results
The groups did not differ in performance on the task. Healthy participants showed activation in the bilateral fusiform gyrus, medial temporal structures, occipital lobe, and inferior frontal cortex relative to the baseline condition. The increase was greater these regions in the right hemisphere than those in the left hemisphere. In the patients with schizophrenia, minimal focal response in the right fusiform gyrus, medial temporal structures, and occipital lobe was observed for the facial perception task relative to the baseline condition. Contrasting patients and comparison subjects revealed voxels in the left medial temporal structures, occipital lobe in which the healthy comparison subjects had significantly greater activation.
Conclusions
Impaired activation was seen in patients with schizophrenia for detection of facial attributes such as sex. Impairment in the medial temporal structure such as amygdale may lead to misunderstanding of social communication and may underlie difficulties in social adjustment experienced by people with schizophrenia.
Studies on community-acquired pneumonia (CAP) and pneumococcal pneumonia (PP) related to the 13-valent pneumococcal conjugate vaccine (PCV13) introduction in Asia are scarce. This study aimed to investigate the epidemiological and microbiological determinants of hospitalised CAP and PP after PCV13 was introduced in Japan. This observational hospital-based surveillance study included children aged ⩽15 years, admitted to hospitals in and around Chiba City, Japan. Participants had bacterial pneumonia based on a positive blood or sputum culture for bacterial pathogens. Serotype and antibiotic-susceptibility testing of Streptococcus pneumoniae and Haemophilus influenzae isolates from patients with bacterial pneumonia were assessed. The CAP hospitalisation rate per 1000 child-years was 17.7, 14.3 and 9.7 in children aged <5 years and 1.18, 2.64 and 0.69 in children aged 5–15 years in 2008, 2012 and 2018, respectively. There was a 45% and 41% reduction in CAP hospitalisation rates, between the pre-PCV7 and PCV13 periods, respectively. Significant reductions occurred in the proportion of CAP due to PP and PCV13 serotypes. Conversely, no change occurred in the proportion of CAP caused by H. influenzae. The incidence of hospitalised CAP in children aged ⩽15 years was significantly reduced after the introduction of PCV13 in Japan. Continuous surveillance is necessary to detect emerging PP serotypes.
Although longitudinal magnetic resonance imaging (MRI) studies have shown that various brain regions undergo progressive tissue loss during the early phases of schizophrenia, regional pattern of these changes remain unclear.
Methods
Longitudinal MRI data were obtained from 18 (12 males and 6 females) patients with first-episode schizophrenia and 20 (11 males and 9 females) healthy controls and at baseline and follow-up with mean scan interval of 2.7 years. To compare gray matter changes over time between patients and controls were evaluated with voxel-based morphometry (VBM) using SPM8 following the longitudinal DARTEL protocol.
Results
In both groups of patient and control longitudinal gray mater reduction was observed in various brain regions including lateral and medial frontal regions and superior temporal region. Excessive decrease in gray matter was found in patients as compared to healthy controls in the left superior temporal region and right inferior frontal region.
Discussion
Our findings suggest that there are differing longitudinal gray matter changes in patients with schizophrenia during the early phases of the illness as compared to healthy individuals.
Research has shown that ADHD symptoms and functional impairment often persist beyond childhood into adulthood. Thus an effective therapy that can be tolerated over long-term use in adults is needed. This is the first long term safety and tolerability study of an adult ADHD medication in Asia.
Objectives:
Assess long-term safety, tolerability, and efficacy of atomoxetine (ATX) in adult Japanese ADHD patients.
Aims:
Demonstrate the safety and tolerability of long-term ATX.
Methods:
ATX (40-120 mg/day) was evaluated based on integrated analyses of a 10 week double-blind (DB) study and a 48 week open-label long term (LT) extension study. Long-term safety and tolerability were assessed by adverse events, discontinuation rate, and vital-signs. Efficacy measures included change from baseline in Conners’ Adult ADHD Rating Scale- Investigator Rated (CAARS-Inv:SV) total symptoms score, behavior Rating Inventory of Executive Function (BRIEF-A), and Adult ADHD/QoL Measure (AAQoL).
Results:
233 patients took ATX (LT mean final prescribed dose: 108.3 mg/day). AEs leading to discontinuations were seen in 37 (15.9%) patients, the most common being nausea in 10 (4.3%) patients. Statistically significant baseline-to-endpoint reductions in mean CAARS-Inv:SV total symptoms score during in the DB study continued throughout the LT study. Similar reductions were seen in BRIEF-A Self Report scores. These findings along with AAQoL results indicated that patients perceived improvements in both QoL and Executive Function.
Conclusions:
Long-term ATX treatment was shown to be generally safe and tolerable in Japanese adult ADHD patients. Results also suggested ATX improved ADHD core symptoms, QoL and Executive Functions.
Reduced white matter integrity in the corpus callosum (CC) has been reported in treatment-resistant depression (TRD). rTMS is assumed to have remote effect on interconnected area with the stimulation site, and this effect is speculated to be one of the therapeutic mechanisms of rTMS treatment. In this preliminary study, we examined changes of callosal fiber integrity in 5 segments of the CC before and after rTMS treatment for TRD.
Methods:
The subjects were 2 patients with treatment-resistant unipolar depression and 1 patient with treatment-resistant bipolar depression, and 24 healthy controls (HC group). The patients underwent 4-week high frequency rTMS to their left DLPFC. In diffusion tensor imaging (DTI) tractography, the CC was divided into 5 segments (orbital, frontal, parietal, temporal, and occipital) based on their cortical projection zones, and fractional anisotropy (FA) value of each segment was estimated. We compared FA in the CC between the patients and the HC groups, and examined changes of FA in the CC after rTMS treatment in the patients.
Results:
The patients showed reduced FA in the frontal, parietal, temporal, and occipital-callosal segments compared to the HC group. All patients responded to the rTMS treatment, and FA in the orbital, frontal, parietal, temporal-callosal segments increased after the rTMS treatment.
Conclusions:
Our results suggest that white matter integrity in the CC is reduced in TRD and that increased white matter integrity in the CC might be related with the therapeutic mechanisms of rTMS treatment.
Impaired self-awareness has been noted as a core feature of schizophrenia. Recent neuroimaging studies examining self-referential process in schizophrenia have yielded inconsistent results. We aimed to examine the self-referential neural network using the self- and other-evaluation tasks in schizophrenia.
Methods
Fifteen schizophrenia patients and fifteen age-, sex- and parental education-matched healthy subjects underwent functional magnetic resonance imaging. Subjects were required to make a decision whether the sentence described their own personal trait (self-evaluation) and that of their close friends (other-evaluation).
Results
Both patients and healthy groups showed significant activation in multiple brain regions including the medial- and lateral-prefrontal, temporal and parietal cortices during self- and other-evaluation tasks. The control subjects showed higher activations in left posterior cingulate and parahippocampal gyri during self-evaluation than other-evaluation, whereas there was no difference in activated regions between self- and other-conditions in the patients. As compared with the controls, the patients showed higher activations in the right superior frontal and right supramarginal gyri during self-evaluation.
Conclusions
These findings provide evidence for neural basis for deficits in self-awareness in schizophrenia and may underlie core clinical symptomatology of schizophrenia.
In bipolar disorder (BD), reduced white matter (WM) integrity in the corpus callosum has been reported, but its detailed localization difference has not been clarified. In this study, we examined fiber integrity in 7 segments of the corpus callosum and their relationships with clinical symptoms in BD.
Methods:
Patients with BD (BD group, n = 17) and age-matched healthy controls (HC group, n = 24) were examined using diffusion tensor imaging tractography. The corpus callosum was divided into 7 segments (orbital frontal, anterior frontal, superior frontal, superior parietal, posterior parietal, temporal, and occipital) based on their cortical projection zones, and fractional anisotropy (FA) value of each segment was estimated. Differences in FA of each segment between the groups were examined using ANOVA with repeated measures. Correlations between FA of each segment and clinical symptoms (HAM-D, YMRS) were assessed using Spearman's rank correlation test in the BD group.
Results:
The BD group showed reduced FA in the orbital frontal, superior frontal, and posterior parietal-callosal segments compared to the HC group. In addition, the BD group showed a significant negative correlation between FA in the orbital frontal-callosal segment and HAM-D scores.
Conclusions:
Our results suggest that WM integrity in the anterior part of the corpus callosum is reduced in BD and that orbital frontal-callosal disintegrity may be related with severity of bipolar depression.
The Murchison Widefield Array (MWA) is an open access telescope dedicated to studying the low-frequency (80–300 MHz) southern sky. Since beginning operations in mid-2013, the MWA has opened a new observational window in the southern hemisphere enabling many science areas. The driving science objectives of the original design were to observe 21 cm radiation from the Epoch of Reionisation (EoR), explore the radio time domain, perform Galactic and extragalactic surveys, and monitor solar, heliospheric, and ionospheric phenomena. All together $60+$ programs recorded 20 000 h producing 146 papers to date. In 2016, the telescope underwent a major upgrade resulting in alternating compact and extended configurations. Other upgrades, including digital back-ends and a rapid-response triggering system, have been developed since the original array was commissioned. In this paper, we review the major results from the prior operation of the MWA and then discuss the new science paths enabled by the improved capabilities. We group these science opportunities by the four original science themes but also include ideas for directions outside these categories.
Flight-deck Interval Management (FIM) is a modern airborne self-spacing technology that improves arrival route throughput and runway utilisation and increases hourly arrival capacity by up to four aircraft per hour and per runway, compared to conventional air traffic controller guided arrivals. The National Aeronautics and Space Administration (NASA) has been the leader in FIM research and formulated a logic that was put to an actual flight test in 2017. Despite the overall success of the project, operational deficiencies concerning the number of speed commands, which led to several recommendations for future research before operational implementation, were discovered. In this study, a new logic that implements a two-stage rule-based selection algorithm was developed to overcome those deficiencies. The proposed logic was compared to NASA’s logic on an arrival in Tokyo International Airport with multiple induced error patterns. The results indicate that the new logic significantly decreases the number of speed commands with only minor aggravations in spacing performance. The results that highlight the strengths and weaknesses of both concepts are discussed, and an outlook on and ideas for future research on FIM and the proposed logic are presented.