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In recent years, studies on circadian control in immunity have been actively conducted in mammals, but little is known about circadian rhythms in the field of fish immunology. In this study, we aimed to analyse the regulation of the diel oscillation of inflammatory cytokine interleukin-1β (il1b) gene expression by core components of the circadian clock in Japanese medaka (Oryzias latipes). The expression of il1b and clock genes (bmal1 and clock1) in medaka acclimated to a 12:12 light (L): dark (D) cycle showed diel rhythm. Additionally, higher expression of il1b was detected in medaka embryo cells (OLHdrR-e3) overexpressing bmal1 and clock1. A significant decrease in il1b expression was observed in OLHdrR-e3 cells after bmal1 knockdown using morpholino oligos. These changes may be mediated by transcriptional regulation via clock proteins, which target the E-box sequence in the cis-element of il1b as identified using luciferase reporter assays. Moreover, LPS stimulation and pathogenic bacterial infection at different zeitgeber time (ZT) under LD12:12 conditions affected the degree of il1b expression, which showed high and low responsiveness to both immuno-stimulations at ZT2 and ZT14, respectively. These results suggested that fish IL-1β exhibited diel oscillation regulated by clock proteins, and its responsiveness to immune-stimulation depends on the time of day.

Background: This study aimed to examine whether robotic self-training improved upper-extremity function versus conventional self-training in mild-to-moderate hemiplegic chronic stroke patients. Methods: Study design was a multi-center, prospective, randomized, parallel-group study comparing three therapist-guided interventions (1-hour sessions, 3×/wk, 10 weeks). We identified 161 prospective patients with chronic, poststroke, upper-limb hemiplegia treated at participating rehabilitation centers. Patients were enrolled between November 29, 2016, and November 12, 2018 in Japan. A blinded web-based allocation system was used to randomly assign 129 qualifying patients into 3 groups: (1) conventional self-training plus conventional therapy (control, N=42); (2) robotic self-training (ReoGo-J) plus conventional therapy (robotic therapy [RT], N=44); or (3) robotic self-training plus constraint-induced movement therapy (N=43). Primary outcome: Fugl-Meyer Assessment for upper-extremity. Secondary outcomes: Motor Activity Log-14 amount of use and quality of movement; Fugl-Meyer Assessment shoulder/elbow/forearm, wrist, finger, and coordination scores; Action Research Arm Test Score; Motricity Index; Modified Ashworth Scale; shoulder, elbow, forearm, wrist, and finger range of motion; and Stroke Impact Scale (the assessors were blinded). Safety outcomes were adverse events. Results: Safety was assessed in 127 patients. An intention-to-treat full analysis set (N=121), and a per-protocol set (N=115) of patients who attended 80% of sessions were assessed. One severe adverse event was recorded, unrelated to the robotic device. No significant differences in Fugl-Meyer Assessment for upper-extremity scores were observed between groups (RT versus control: −1.04 [95% CI, −2.79 to 0.71], P =0.40; RT versus movement therapy: −0.33 [95% CI, −2.02 to 1.36], P =0.90). The RT in the per-protocol set improved significantly in the Fugl-Meyer Assessment for upper-extremity shoulder/elbow/forearm score (RT versus control: −1.46 [95% CI, −2.63 to −0.29]; P =0.037). Conclusions: Robotic self-training did not improve upper-limb function versus usual self-training, but may be effective combined with conventional therapy in some populations (per-protocol set). Registration: URL: https://www.umin.ac.jp/ctr ; Unique identifier: UMIN000022509.

A pseudotuberculosis pathogen, Photobacterium damselae subsp. piscicida (Pdp), has caused enormous economic damage to yellowtail aquaculture in Japan. The Ivy gene has been discovered in plasmid of Pdp, and it has been proposed that it may help bacteria evade lysozyme-mediated lysis during interaction with an animal host. However, the lysozyme-inhibiting activity of Pdp-derived Ivy (Ivy-Pdp) is unknown, and it is unclear whether it acts as a virulence factor for host biophylaxis. In this study, the inhibitory effect of Ivy-Pdp on lysozyme was evaluated by expressing and purifying the recombinant Ivy-Pdp protein (rIvy-Pdp). The rIvy-Pdp protein inhibited hen egg white lysozyme activity in an rIvy-Pdp-concentration-dependent manner, and its inhibitory effect was similar under different temperature and pH conditions. The serum and skin mucus of the yellowtail (which is the host species of Pdp), Japanese flounder, and Nile tilapia showed bacteriolytic activity. In contrast, the addition of rIvy-Pdp inhibited the lytic activity in the serum of these fish species. In particular, it significantly inhibited lytic activity in the serum and skin mucus of Nile tilapia. On the basis of these results, we suggest that Ivy-Pdp is a temperature- and pH-stable lysozyme inhibitor. Additionally, Ivy-Pdp inhibited the lytic activity of lysozyme, which is involved in host biophylaxis. In summary, we inferred that Ivy-Pdp is an important factor that diminishes the sterilization ability of C-type lysozyme when Pdp infects the host.

Capsizing is one of the worst scenarios in oceangoing vessels. It could lead to a high number of fatalities. A considerable number of studies have been conducted until the 1980s, and one of the discoveries is the weather criterion established by the International Maritime Organization (IMO). In the past, one of the biggest difficulties in revealing the behavior of ship-roll motion was the nonlinearity of the governing equation. On the other hand, after the mid-1980s, the complexity of the capsizing problem was uncovered with the aid of computers. In this study, we present the theoretical backgrounds of the capsizing problem from the viewpoint of nonlinear dynamics. Then, we discuss the theoretical conditions and mechanisms of the bifurcations of periodic solutions and numerical attempts for the bifurcations and capsizing.

Background Hypertensive emergency is a critical disease that causes multifaceted sequelae, including end-stage kidney disease and cardiovascular disease. Although the renin-angiotensin-aldosterone (RAA) system is enormously activated in this disease, there are few reports that attempt to characterize the effect of early use of RAA inhibitors (RASi) on the temporal course of kidney function. Methods This retrospective cohort study was conducted to clarify whether the early use of RASi during hospitalization offered more favorable benefits on short-term renal function and long-term renal prognosis in patients with hypertensive emergencies. We enrolled a total of 49 patients who visited our medical center with acute severe hypertension and multiple organ dysfunction between April 2012 and August 2020. Upon admission, the patients were treated with intravenous followed by oral antihypertensive drugs, including RASi and Ca channel blockers (CCB). Kidney function as well as other laboratory and clinical parameters were compared between RASi-treated and other antihypertensive drugs-treated group over 2 years. Results Antihypertensive treatment effectively reduced blood pressure from 222 ± 4/142 ± 3 to 140 ± 3/87 ± 2 mmHg at 2 weeks and eGFR was gradually restored from 33.2 ± 3.3 to 41.1 ± 4.1mL/min/1.73m2 at 1 year. The renal effect of antihypertensive drugs was particularly conspicuous when RASi was started in combination with other conventional antihypertensive drugs at the early period of hospitalization (2nd day [IQR: 1-5.5]) and even in patients with moderately to severely diminished eGFR (2) on admission. In contrast, CCB modestly restored eGFR during the observation period. Furthermore, renal survival probabilities were progressively deteriorated in patients who had manifested reduced eGFR (2) or massive proteinuria (urine protein/creatinine ≥ 3.5 g/gCr) on admission. Early use of RASi was associated with a favorable 2-year renal survival probability (0.90 [95%CI: 0.77-1.0] vs. 0.63 [95%CI: 0.34–0.92] for RASi(+) and RASi(-), respectively, p = 0.036) whereas no apparent difference in renal survival was noted for CCB, β-blocker, α-blockers, or diuretics. Conclusions Early use of RASi contributes to the renal functional recovery from acute reduction in eGFR among patients with hypertensive emergencies. Furthermore, RASi offers more favorable effect on 2-year renal survival, compared with other antihypertensive drugs.

The time derivative of acceleration is called a jerk, which is an important property to evaluate ride comfort in elevators, cars, and so on. Likewise, evaluation of motion sickness or ride comfort on a vessel could be achieved by this jerk property in the future. In this paper, we utilize the PDF Line Integral Method (PLIM), which was newly contrived in our previous research, for calculating not only roll angular acceleration but also roll angular jerk. The derivation of this theory, as well as numerical comparison with Monte Carlo simulation (MCS) results, are presented. Although the utilized restoring curve (GZ curve) exhibits strong asymmetricity, the proposed method successfully calculates roll angular jerk for such a condition. Since roll angular jerk is a high-order differential property, the biggest advantage of PLIM is that it only requires the information of roll and roll rate joint probability density function (PDF) to provide the PDF of jerk.

A methodology for predicting the probability density function of roll motion for irregular beam seas is developed in the author’s previous research. In this paper, two methods for the prediction of the probability density function (PDF) of the rolling amplitude are examined. One of these methods is an approach based on a non-Gaussian PDF with the use of the equivalent linearization and the moment method, which has been used by Maki in the field of naval architecture. In the framework of this method, the instantaneous joint PDF of the roll and roll rate can be calculated. Thereby, the transformation from the joint PDF to the PDF of the total energy H is necessary. In this paper, the transformation from the joint PDF of instantaneous roll and rate to the PDF of H was conducted. The other method is the energy-based stochastic averaging method, whereby the PDF of the total energy H is determined from which the roll amplitude is calculated. It is noteworthy that the proposed theory aims to predict the PDF of the amplitude of the vessel due to wind or flooding. For such conditions, the restoring curve (GZ curve) has asymmetricity. To take into account this asymmetricity, a new theory for the transform of the PDF of the total energy H to the PDFof amplitude is proposed. The obtained theoretical results show almost complete agreement, and both of the two theoretical methods i.e., the energy-based stochastic averaging method and the non-Gaussian PDF method with the use of the equivalent linearization and moment method, show equivalent prediction performance even in the asymmetric condition.

Background: Although anti-TNF-α monoclonal antibody (BP) agents are widely used as an established treatment tool for refractory ulcerative colitis (UC), whether leukocytapheresis/granulocytapheresis (L/G-CAP) has similar beneficial impact on the disease activity remains undetermined. Furthermore, the costs defrayed for the treatment with these two modalities have not been compared. Methods: We retrospectively evaluated whether L/G-CAP offered sustained beneficial effects over 2-year period. The patients who had moderately to severely active UC (Rachmilewitz Clinical Activity Index (CAI)≧5) and were treated with a series (10 sessions) of L/G-CAP (n=19) or BP (n=7) as an add-on therapy to conventional medications were followed. Furthermore, the cost-effectiveness pertaining to the treatment with L/G-CAP and BP was assessed over 12 months. Results: At baseline, L/G-CAP and BP groups manifested similar disease activity (CAI, L/G-CAP; 7.0 [6.0-10.0], BP; 10.0 [6.0-10.0], p=0.207). The L/G-CAP and BP treatment suppressed the activity, with CAI 1 or less attained on day 180. When the L/G-CAP group was dichotomized into L/G-CAP-high and L/G-CAP-low group based on CAI values (≥3 or Conclusions: L/G-CAP is as effective as BP in a substantial number of patients over two years. The cost for the treatment of UC favors L/G-CAP although the correction of anemia may prefer BP. Thus, L/G-CAP can effectively manage the disease activity with no additional implementation for two years although further therapeutic modalities might be required in a certain population with high CAI observed on day 365. Trial registration: This study is a retrospective analysis evaluating the long-term efficacy of L/G-CAP and anti-TNF-α monoclonal antibody agents on the disease activity during a total of two years, and also assessing the costs of the treatment for UC over 12-month period (UMIN trial No. 000036954). The study was approved by the Ethics Committee of Tokyo Bay Urayasu Ichikawa Medical Center (Chiba, institutional approval No. 376) and Keiyu Hospital (Yokohama, Kanagawa, institutional approval No. R3-26) with waiver of the requirement for obtaining informed consent, and was conducted in accordance with the Declaration of Helsinki. Information from medical records was anonymized and de-identified prior to final analysis.

Coral reef aorta (CRA), a rare disease, is characterized by severe calcification of the juxta-renal and suprarenal aorta that grows into the lumen and leads to severe stenosis. A 70-year-old woman with refractory hypertension and lower limb claudication presented with hypertension and congestive heart failure. Treatment with vasodilators and diuresis led to oliguria and exacerbated kidney function, while her congestion remained. Abdominal computerized tomography showed a bulky, irregular localized supra-renal aortic calcification with stenosis. A peripheral artery ultrasound and angiography showed no occlusive lesions in the distal run-off vessels. Based on her medical history and the unique aspects of the localized calcified lesion, CRA was diagnosed. We suspected that the congestive heart failure, refractory hypertension, and renal failure resulted from the supra-renal aortic stenosis. Because she developed oliguria with diuretics and vasodilators, we performed an open graft replacement with a thoracoabdominal approach. The reddish-brown calcified mass came off easily and was very fragile. The postoperative course was uneventful, and her heart and renal failure were completely resolved. This is the first report showing the fragility of CRA. Considering its fragility, catheter treatment may need to be avoided to prevent distal embolism.

The prevention of excessive roll acceleration is one of the fundamental requirements of an oceangoing vessel at sea. In this paper, aiming at this requirement, we propose a new theoretical method for calculating roll angular acceleration, called “PDF line integral method.”. This paper presents the derivation of this method and a numerical comparison with Monte Carlo simulation (MCS) results; also, its validity is shown. Although the utilized GZ curve (restoring curve) exhibits strong asymmetricity, the proposed method can provide for such a condition. With only the information of roll and roll rate joint probability density function (PDF), this method can approximately calculate the roll angular acceleration, which is a high-order differential property. In addition, a relatively good agreement is achieved between the theory and MCS results.

Interleukin (IL)-17 is a proinflammatory cytokine and plays essential roles in adaptive and innate immune responses against bacterial and fungal infections. Especially in mammalian mucosal tissues, it is well known that innate immune responses via IL-17A and IL-17F, such as the production of antimicrobial peptides, are very important for microbiota control. In contrast, interesting insights into the functions of IL-17 have recently been reported in several teleost species, although little research has been conducted on teleost IL-17. In the present review, we focused on current insights on teleost IL-17 and speculated on the different or consensus parts of teleost IL-17 signaling compared to that of mammals. This review focuses on the role of teleost IL-17 in intestinal immunity. We expect that this review will encourage a further understanding of the roles and importance of IL-17 signaling in teleosts.

Mucosal tissue forms the first line of defense against pathogenic microorganisms. Cellular damage in the mucosal epithelium may induce the interleukin (IL)-22-related activation of many immune cells, which are essential for maintaining the mucosal epithelial barrier. A previous study on mucosal immunity elucidated that mammalian IL-22 contributes to mucus and antimicrobial peptides (AMPs) production and anti-apoptotic function. IL-22 has been identified in several teleost species and is also induced in response to bacterial infections. However, the roles of IL-22 in teleost immunity and mucus homeostasis are poorly understood. In this study, Japanese medaka (Oryzias latipes) was used as a model fish. The medaka il22, il22 receptor A1 (il22ra1), and il22 binding protein (il22bp) were cloned and characterized. The expression of medaka il22, il22ra1, and il22bp in various tissues was measured using qPCR. These genes were expressed at high levels in the mucosal tissues of the intestines, gills, and skin. The localization of il22 and il22bp mRNA in the gills and intestines was confirmed by in situ hybridizations. Herein, we established IL-22-knockout (KO) medaka using the CRISPR/Cas9 system. In the IL-22-KO medaka, a 4-bp deletion caused a frameshift in il22. To investigate the genes subject to IL-22-dependent regulation, we compared the transcripts of larval medaka between wild-type (WT) and IL-22-KO medaka using RNA-seq and qPCR analyses. The comparison was performed not only in the naïve state but also in the dextran sulfate sodium (DSS)-exposed state. At the transcriptional level, 368 genes, including immune genes, such as those encoding AMPs and cytokines, were significantly downregulated in IL-22-KO medaka compared that in WT medaka in naïve states. Gene ontology analysis revealed that upon DSS stimulation, genes associated with cell death, acute inflammatory response, cell proliferation, and others were upregulated in WT medaka. Furthermore, in DSS-stimulated IL-22-KO medaka, wound healing was delayed, the number of apoptotic cells increased, and the number of goblet cells in the intestinal epithelium decreased. These results suggested that in medaka, IL-22 is important for maintaining intestinal homeostasis, and the disruption of the IL-22 pathway is associated with the exacerbation of inflammatory pathology, as observed for mammalian IL-22.

UVSOR is a Japanese low-energy synchrotron light source that has been operational since 1983. It has 750 MeV electron beam energy and a circumference of 53 m. The machine has undergone two major upgrades and is now called UVSOR-III, with a moderately small emittance of 17 nm·rad and is operated in the top-up mode at 300 mA. It has six undulators. Three in-vacuum undulators provide high-brightness VUV-SX light to the beamlines BL3U, BL4U, and BL6U. BL3U and BL4U are actively used for chemistry and life sciences using in situ and operando measurements, such as soft X-ray absorption and photoelectron spectroscopy. Since 2020, a unique photoelectron analyzer called the Momentum Microscope has been in operation in BL6U. Two variable polarization undulators provide high-brightness VUV light to the beamlines, BL5U and BL7U, which are used for solid-state physics through angle- and spin-resolved photoelectron spectroscopy. BL1U is equipped with two APPLE-II undulators in tandem and is used for various research purposes, including laser Compton scattering gamma rays. In addition to these beamlines, eight beamlines are operational which use bending magnet radiation, ranging from THz to tender X-rays. In 38 years of operation, we have dealt with and properly resolved machine problems, such as water leakage from magnet coils and cooling water flow paths in ultrahigh vacuum. Considering the machine’s declining competitiveness as a light source due to its aging and emerging demands in the low-energy area, we have started a design study on the future plan, as well as discussing it closely with the user community.

Rhodococcus equi was isolated from the gastrointestinal contents of earthworms (family Megascolecidae) and their surrounding soil collected from pastures of two horse-breeding farms in Aomori Prefecture, outdoor pig pens, forest in Towada campus, orange groves and forest where wild boars (Sus scrofa) are established in Tanabe, Wakayama Prefecture. The number of R. equi in the lower gastrointestinal contents of 23 earthworms collected from our campus was significantly larger than that of the upper gastrointestinal content. The mean numbers of R. equi from the gastrointestinal contents of earthworms collected from the various places were 2·3-fold to 39·7-fold more than those of the surrounding soil samples. In all, 1771 isolates from the earthworms and 489 isolates from the soil samples were tested for the presence of vapA and vapB genes using polymerase chain reaction. At the horse-breeding farm N, 9 of the 109 isolates (8·3%) from the earthworms and 7 of the 106 isolates (6·6%) from the soil samples were positive for the vapA gene. At the University's forest, one of the 250 isolates (0·4%) from the gastrointestinal contents of the earthworm was positive for the vapB gene. These results revealed that R. equi can be found in significant quantities in the gastrointestinal contents of earthworms, suggesting that they act as an accumulator of R. equi in the soil environment and as a source or reservoir of animal infection.

The development of the second generation intact stability criteria is ongoing in the International Maritime Organization, and the level 1 and 2 criteria are almost agreed. However, validation/verification studies of the level 2 criteria remain to be insufficient. Herein, the mean frequencies of Grim's effective waves are used and compared with the draught of the second check of the level 2 criteria for parametric roll. Therefore, the encounter frequency assumption used in the draught second check is verified. Additionally, it is shown that the number of samples of operational conditions should be at least 24.

To date, little information is available on the effects of circadian oscillation on immune regulation in lower vertebrates, such as teleost fish. In the present study, regulation of circadian oscillation of inflammatory cytokine TNF-α gene expression by clock gene was investigated using model fish medaka (Oryzias latipes). Firstly, structural analysis of clock genes was performed, which revealed that medaka BMAL1 and CLOCK1 conserve functionally important domains, such as basic helix-loop-helix (bHLH) and period-aryl hydrocarbon receptor nuclear translocator-single-minded (PAS), seen in their counterparts in other vertebrates. Expression of medaka Bmal1, Clock1, and Per1 genes was confirmed in central and peripheral tissues. Moreover, the expression of these clock genes and TNF-α genes in medaka acclimated to a 12:12 light (L) - dark (D) cycle showed circadian oscillation. In addition, higher expression of TNF-α gene was detected in medaka embryo cells (OLHdrR-e3) overexpressing Bmal1 and Clock1 genes. It was suggested that this increase was mediated by transcriptional regulation by clock proteins, which target E-box sequence in the cis-element of TNF-α gene as was detected by luciferase reporter gene assay. Moreover, in vitro head kidney stimulation with LPS at different zeitgeber time (ZT) under LD12:12 condition affected the degree of TNF-α gene expression, which shows high and low responsiveness to LPS stimulation at ZT18 and ZT10, respectively. These results suggested that fish TNF-α exhibited circadian oscillation regulated by clock proteins and its responsiveness against immune-stimulation depends on time zone.

Photoluminescence (PL) emission of colloidal PbSe/CdSe core/shell quantum dots (QDs, CdSe shell thickness: 0.2 nm) at the lowest exciton state was investigated at room temperature and varying inter-QD distance (L = 7-240 nm) by changing the QD concentration. A distinct enhancement of the valley splitting of PbSe QDs was observed upon reducing L. Simultaneously, there was a redshift in the emission due to Forster resonance energy transfer (FRET), when the L value was still sufficiently large (7 nm ≤ L ≤ 50 nm) so that the wave functions of different QDs do not overlap. The enhanced valley splitting under no apparent external field is quite interesting as a method to control the valley splitting. The electronic coupling leading to FRET may enhance the valley splitting, because it occurs in an identical range of L.

In the intestine, the host must be able to control the gut microbiota and efficiently absorb transiently supplied metabolites, at the risk of enormous infection. In mammals, the inflammatory cytokine interleukin (IL)-17A/F is one of the key mediators in the intestinal immune system. However, many functions of IL-17 in vertebrate intestines remain unclarified. In this study, we established a gene-knockout (KO) model of IL-17 receptor A1 (RA1), an IL-17A/F receptor, in Japanese medaka (Oryzias latipes) using genome editing technique and the phenotypes were compared to wild type (WT) based on transcriptome analyses. Upon hatching, homozygous IL-17RA1-KO medaka mutants showed no significant morphological abnormality. However, after 4 months, significant weight decreases and reduced survival rates were observed in IL-17RA1-KO medaka. Comparing gene-expression patterns in WT and IL-17RA1-KO medaka revealed that various metabolism- and immune-related genes were significantly down-regulated in IL-17RA1-KO medaka intestine, particularly genes related to mevalonate metabolism (mvda, acat2, hmgcs1, and hmgcra) and genes related to IL-17 signaling (such as il17c, il17a/f1, and rorc) were found to be decreased. These findings show that IL-17RA regulated immune- and various metabolism-related genes in the intestine for maintaining the health of Japanese medaka.

Recent randomized trials demonstrating the beneficial effects of sodium-glucose cotransporter 2 inhibitors (SGLT2is) in type 2 diabetes suggest that early reductions in eGFR upon initiation of SGLT2i therapy are associated with improved renal outcomes. Multiple concomitant medications, including antidiabetic and antihypertensive agents, are commonly used, however, which may modify the renal hemodynamic action of SGLT2is. Here we found that background treatment with metformin diminished the SGLT2i-induced reductions in eGFR after 3 months of SGLT2i therapy in patients with type 2 diabetes and hypertension (−2.29 ± 0.90 vs −5.85 ± 1.27 mL/min/1.73 m2 for metformin users (n = 126) and nonusers (n = 97), respectively). Other antidiabetic agents (DPP4 inhibitors, sulfonylureas and insulin) had no effect on the eGFR response to SGLT2is. Antihypertensive drugs, including calcium channel blockers (CCBs) and β blockers, did not affect the SGLT2i-induced changes in eGFR, whereas renin-angiotensin system inhibitors (RASis) tended to enhance this response (p = 0.059). Next, we evaluated the interaction between metformin and RASis in the eGFR responses to SGLT2is. Under no background treatment with RASis, metformin abrogated the eGFR response to SGLT2is, but this response was preserved when RASis had been given along with metformin (decreases of 0.75 ± 1.28 vs. 4.60 ± 1.15 mL/min/1.73 m2 in eGFR, p = 0.028). No interaction between metformin and insulin or between metformin and DPP4 inhibitors was observed. In conclusion, metformin blunts the SGLT2i-induced decrease in eGFR, but coadministration of RASis ameliorates this response. Furthermore, the inability of CCBs to modify the SGLT2i-induced reduction in eGFR suggests that the SGLT2i-induced renal microvascular action is mediated predominantly by postglomerular vasodilation rather than preglomerular vasoconstriction.

The growing interest in deep learning has created a demand to compile computation graphs to accelerate execution and to deploy applications on various devices. Modern deep learning frameworks construct computation graphs dynamically. This gives rise to the problem of inferring types of dynamic computation graphs. Two approaches are known. One of them is a dynamic approach that constructs the computation graph from the execution trace of an actual input. While this approach is straightforward, the results of the shape inference will consist of only concrete values and is often difficult for users to interpret. The other one performs static analysis over the source program. This method can produce symbolic shape inference results but suffers from the dynamic nature of the host programming language Python. In this paper, we propose a novel approach for type, shape, and symbolic shape inference of dynamic computation graphs as a mixture of the above two methods. We present results of applying our prototype inference engine for networks written with PyTorch and demonstrate its effectiveness for nontrivial networks.