Discrimination of object information by bat echolocation deciphered from acoustic simulations.

High-precision visual sensing has been achieved by combining cameras with deep learning. However, an unresolved challenge involves identifying information that remains elusive for optical sensors, such as occlusion spots hidden behind objects. Compared to light, sound waves have longer wavelengths and can, therefore, collect information on occlusion spots. In this study, we investigated whether bats could perform advanced sound sensing using echolocation to acquire a target's occlusion information. We conducted a two-alternative forced choice test on Pipistrellus abramus with five different targets, including targets with high visual similarity from the front, but different backend geometries, i.e. occlusion spots or textures. Subsequently, the echo impulse responses produced by these targets, which were difficult to obtain with real measurements, were computed using three-dimensional acoustic simulations to provide a detailed analysis consisting of the acoustic cues that the bats obtained through echolocation. Our findings demonstrated that bats could effectively discern differences in target occlusion spot structure and texture through echolocation. Furthermore, the discrimination performance was related to the differences in the logarithmic spectral distortion of the occlusion-related components in the simulated echo impulse responses. This suggested that the bats obtained occlusion information through echolocation, highlighting the advantages of utilizing broadband ultrasound for sensing.

Incidence of Bowel Wall Swelling Induced by Iodine-Contrast Media and Its Association With Gastrointestinal Manifestation.

PURPOSE: The aim of this study was to investigate the incidence of bowel wall swelling after iodine-contrast media injection and its relationship with gastrointestinal symptoms. METHODS: The incidence of bowel wall swelling was examined in 75 patients who showed adverse reactions to iodine-contrast media (AR[+] group) and 75 controls without adverse reactions (AR[-] group). Bowel wall swelling was identified if there was increased wall thickness on postcontrast computed tomography when compared with precontrast computed tomography. Swelling less than 2-fold of the original wall thickness was defined as grade 1 bowel angioedema, and swelling more than 2-fold was defined as grade 2. RESULTS: The incidence of bowel wall swelling was significantly higher in the AR(+) group (26.6%) than in the AR(-) group (10.6%) ( P = 0.01). Grade 1 bowel wall swelling was observed in 12.0% and 10.7% of AR(+) and AR(-) groups, respectively, whereas grade 2 was observed in 14.7% and 0%, respectively. Bowel wall swelling was observed in the duodenum and jejunum but not in the stomach, ileum, or colon in any patient in either group. In the AR(+) group, nausea and/or vomiting was observed in 15 patients, among whom bowel wall swelling was observed in 9 patients (60%). The frequency of nausea and/or vomiting was significantly higher in the patients with bowel wall swelling (45.0%, 9/20) compared with those without (10.9%, 6/55). CONCLUSION: Bowel wall swelling was more frequent and severe in patients with adverse reactions to iodine-contrast media than those without and was associated with nausea and/or vomiting.

Simulation of ultrasonically induced electrical potentials in bone.

Low-intensity pulsed ultrasound treatment is known to shorten the healing period of bone fractures by 30%-40%, but the initial mechanism of the healing process remains unknown. One possible mechanism is related to the piezoelectricity of bone. However, the complex geometry of bones results in inherent challenges to evaluating electric fields induced therein. Therefore, in this study, we investigate the piezoelectric responses of bones by using simulations to study the wave propagation and induced potentials in bone, according to the piezoelectric finite-difference time-domain (PE-FDTD) method. First, we verify the suitability of the PE-FDTD method by comparing the simulated electric field results with the experimental data obtained by an ultrasound receiver using bone as the piezoelectric element. Next, ultrasound irradiation into a real bone model (the radius of a 66-year-old woman) is simulated at different incident angles. At normal incidence and off-axis incidence (45°), the maximum electric field strength was 4.3 and 5.6 mV/cm, respectively. We also present evidence of significant shear wave contribution to the induced potential. The results of this study confirm the existence of ultrasonically induced potentials in heterogenous bones with complex shapes, equal in magnitude to potentials generated in electrically stimulated bone healing.

Effect of bat pinna on sensing using acoustic finite difference time domain simulation.

The practicality of the finite-difference time-domain (FDTD) method was confirmed by comparing head-related transfer functions obtained from a three-dimensional (3D) digital model of a bat (Rhinolophus ferrumequinum nippon) head with acoustic experiments using a 3D printed physical model. Furthermore, we simulated the auditory directionality using a 3D digital model that was modified based on the pinna movement of a bat during echolocation and found that the alternating movements of the left and right pinna result in a binaural sound pressure difference for vertical sources. Using the FDTD method, suitable for simulating acoustics in large spaces, we could analyze in detail the binaural echoes that bats receive and the acoustic cues they use for echolocation.

Reconstruction of echoes reaching bats in flight from arbitrary targets by acoustic simulation.

Echolocating bats perceive their environment by emitting ultrasonic pulses and listening to echoes that are reflected back from their surroundings. Behavioral decisions of bats are mainly dependent on echo information, and acoustical analysis of echoes is useful for understanding their behavioral decisions. To date, echoes have been measured using a telemetry microphone mounted on the bat's head; however, due to technical difficulties, it was not enough to measure all the echoes reaching the bats in flight. In this paper, we propose an approach to reconstruct the echoes of bats in flight using finite-difference time-domain (FDTD) method simulations based on the measured flight path, speed, and sound information from behavioral experiments. As a result, echoes from any target in flight can be correctly reconstructed, including the Doppler effect. We also analyzed the spatiotemporal transition among attended walls for Doppler shift compensation (DSC) during circling flight in the context of DSC behavior and found that the bats switch their attention to different walls and focus on the wall ahead of them in the direction of flight.

Analysis of echolocation behavior of bats in "echo space" using acoustic simulation.

BACKGROUND: Echolocating bats use echo information to perceive space, control their behavior, and adjust flight navigation strategies in various environments. However, the echolocation behavior of bats, including echo information, has not been thoroughly investigated as it is technically difficult to measure all the echoes that reach the bats during flight, even with the conventional telemetry microphones currently in use. Therefore, we attempted to reproduce the echoes received at the location of bats during flight by combining acoustic simulation and behavioral experiments with acoustic measurements. By using acoustic simulation, echoes can be reproduced as temporal waveforms (including diffracted waves and multiple reflections), and detailed echo analysis is possible even in complex obstacle environments. RESULTS: We visualized the spatiotemporal changes in the echo incidence points detected by bats during flight, which enabled us to investigate the "echo space" revealed through echolocation for the first time. We then hypothesized that by observing the differences in the "echo space" before and after spatial learning, the bats' attentional position would change. To test this hypothesis, we examined how the distribution of visualized echoes concentrated at the obstacle edges after the bats became more familiar with their environment. The echo incidence points appeared near the edge even when the pulse direction was not toward the edge. Furthermore, it was found that the echo direction correlated with the turn rate of the bat's flight path, revealing for the first time the relationship between the echo direction and the bat's flight path. CONCLUSIONS: We were able to clarify for the first time how echoes space affects echolocation behavior in bats by combining acoustic simulations and behavioral experiments.

Simulation of pulsed ultrasonic diffraction in viscous fluids using transmission line matrix method.

Ultrasonic fields propagating in viscous media undergo changes in shape due to diffraction, attenuation, and dispersion. Until now, some implementations in the transmission line matrix (TLM) method has been developed to simulate either diffraction or attenuation but never both. In this work, the quadratic frequency dependence of the absorption coefficient as well as the dispersive effect of a viscous fluid are introduced in the TLM method. The idea is to decompose the emitted wave into its components at different frequencies using Fourier transform. Then, dispersion and attenuation effects are considered for each wave component separately before superposing them to get the required acoustic response. This is possible because each one of them is characterized by a constant absorption coefficient and propagates at a single speed. This TLM model has been applied to the diffracted ultrasonic field by a circular transducer radiating a short pulse in a viscous fluid. The obtained waveforms are interpreted in terms of plane and edge waves. A study of the influence of the most important parameters on the waveform of the detected ultrasonic pulses is performed. The numerical results obtained highlight the attenuation effect on the waves' shapes and the influence of the dispersion on their arrival times.

A Molecularly Modulated Mode-Locked Laser.

A mode-locked laser operating at a frequency over 10 THz is reported, which is three orders of magnitude greater than a standard mode-locked laser. The system used molecules with a Raman gain as an amplifier, while coherent molecular motions were used for optical modulation. Molecules in a high-finesse optical cavity modulated a continuous-wave beam to produce a train of ultrashort optical pulses at a repetition rate corresponding to the frequency of molecular motion. Phase-locking was achieved by an appropriate compensation of the total dispersion of the optical cavity. Thus, the oscillating multiple longitudinal modes were all coupled under phase-matching conditions of parametric four-wave mixing.

M1 macrophage infiltrations and histological changes in the liver after portal vein embolization using fibrinogen and OK432 in the rat.

The mechanism of anti-tumor effect of transarterial Immuno-Embolization (TIE) using OK-432 has not been well elucidated. In this study, we aimed to investigate the tissue injury and immune response after portal venous embolization (PVE) with/without OK-432. Embolic materials (L group: lipiodol, LF group: lipiodol+fibrinogen, LO group: lipiodol+OK-432, LFO group: lipiodol+fibrinogen+OK-432) were administered via the right portal vein in Wistar rats. The histological findings in LFO group demonstrated liver damage with severe architectural changes. The concentrations of CD68(+) cells were observed in a time-dependent manner; it was significantly increased in the LO group on day 1 and in the LFO group on day 3. CD68(+)CD163(-) macrophages significantly increased in the LFO group on day 7 (P<0.05). In conclusion, PVE with fibrinogen and OK-432 markedly increased the CD68(+)CD163(-) infiltrating macrophages around the peri-portal area in the liver. This novel technique could be applied as immune-enhanced chemo-embolization of liver tumors.

Role of intratumoral infiltrating macrophages after transarterial immunoembolization for hepatocellular carcinoma.

BACKGROUND: Preoperative transarterial immunoembolization (TIE) for hepatocellular carcinoma (HCC) is effective for preventing recurrence. We aimed to investigate the intratumoral and peritumoral M1 macrophage-induced immune response following TIE treatment. METHODS: We compared 13 patients treated with TIE between 2003 and 2009 (TIE group) and 13 patients treated with surgery alone during the same period of time at our institute (control group) using an immunohistological study with CD68 and CD163 antibodies. RESULTS: No significant differences in clinicopathological characteristics, except for surgical time, were observed between the two groups. The 3-year recurrence-free survival outcome of the TIE group was quite different from that of the control group (100% vs. 38.5%, P = 0.034). In the histological investigation, lytic necrosis and coagulation necrosis of the main tumor along with the presence of multinuclear giant cells were observed in 10 of the 13 patients in the TIE group. The immunohistological study showed that not only the numbers of intratumoral CD68(+) cells, but also the numbers of intratumoral and peritumoral CD8(+) cells were significantly increased in the TIE group. CONCLUSIONS: The suppression of tumor recurrence induced by preoperative TIE might be induced by intratumoral M1 macrophages that are activated by OK-432 and fibrinogen.

Continuous-wave phase-matched molecular optical modulator.

In optical modulation, the highest available modulation rate is basically limited to the GHz frequency range at best. This is because optical modulation is often performed using electro-optic or acousto-optic effects that require application of an external signal to solid-state nonlinear optical materials. Here we describe optical modulation of continuous-wave radiation at frequencies exceeding 10 THz based on ultrafast variation of molecule polarizability arising from coherent molecular motion. The optical modulation efficiency is extensively enhanced by fulfilling phase-matching conditions with the help of dispersion control of the optical cavity, generating sidebands with a highest ratio of 7.3 × 10(-3). These results will pave the way for development of versatile optical modulation-based techniques in a wide range of research fields in optical sciences, such as mode-locked lasers operating in the THz range.

[Pancreatic Adenosquamous Carcinoma That Developed after Resection of IPMA in the Pancreatic Tail].

Pancreatic adenosquamous carcinoma coexisting with intraductal papillary mucinous neoplasm(IPMN)is extremely rare. We report a rare case of pancreatic adenosquamous carcinoma that developed after resection of intraductal papillary mucinous adenoma(IPMA). A 67-year-old man was suspected of having a pancreatic cystic lesion. MRCP demonstrated a cystic lesion measuring 25mm in the pancreatic tail, which had an enhanced nodule. We therefore diagnosed branch duct type IPMN of the pancreas. Although pancreatic juice cytology did not indicate malignancy, we performed laparoscope-assisted distal pancreatectomy. The reason why the IPMN lesion had an enhanced nodule. The histopathological diagnosis was IPMA without malignancy. One year and 5 months after surgery, blood analysis showed an elevated tumor marker level, and abdominal CT demonstrated a pancreatic head tumor with lymphadenopathy. EUS-FNA was performed and the patient was diagnosed with pancreatic adenosquamous carcinoma based on immunohistochemical staining. We administered chemotherapy with gemcitabine and S-1. After 3 courses of this chemotherapy, the size of the pancreatic tumor and the tumor marker level decreased. The patient achieved a partial response. He is still receiving chemotherapy after 7 courses.

Remnant left lobe torsion causing hepatic venous outflow obstruction after hepatic right lobectomy for giant hepatocellular carcinoma: report of a case.

We report the case of a 67-year-old man with remnant left liver torsion causing acute hepatic venous outflow obstruction after right hepatectomy for giant hepatocellular carcinoma, which was successfully treated with surgery. After the primary surgery, he developed significant liver dysfunction and renal failure. Doppler ultrasonography disclosed gradual reduction of hepatic perfusion. Abdominal computed tomography revealed that the swollen remnant liver was dislocated in the right subphrenic space. After surgical repositioning of the left lobe into its anatomical position, the hepatic congestion immediately disappeared, and the hemodynamic parameters improved. The falciform and round ligaments were fixed to the anterior abdominal wall to keep the remnant liver in the anatomical position. His postoperative course was uneventful. Doppler ultrasonography was useful to assess hepatic perfusion for screening of acute hepatic venous outflow obstruction and abdominal computed tomography is definitive for diagnosis. Fixation of remnant liver may be effective for preventing hepatic venous outflow obstruction after right hepatectomy, particularly for giant tumor.

[A case of two re-resections for peritoneal recurrence of pancreatic cancer].

A 63-year-old man underwent subtotal stomach-preserving pancreaticoduodenectomy and intraoperative radiation therapy for pancreatic head cancer (Stage IVa, JPS). Subsequently, he received adjuvant chemotherapy including gemcitabine (GEM). A peritoneal recurrence appeared adjacent to the right colon and the lower pole of the right kidney. He received chemotherapy including S-1 and GEM+S-1. Since the recurrent lesions were localized, he underwent resection for the recurrence lesions 2 years and 9 months after surgery. The resection was R1, and re-recurrence appeared in the lower pole of the right kidney. After chemotherapy and chemoradiotherapy, he underwent re-resection for the recurrence 4 years and 3 months after the first surgery. Three months after re-resection, multiple liver metastases appeared in the bilateral lobes. Reoperation can be one of the multidisciplinary management options for local recurrence of pancreatic cancer under specific conditions.

Increased IL-17 production correlates with immunosuppression involving myeloid-derived suppressor cells and nutritional impairment in patients with various gastrointestinal cancers.

Although a causal relationship between inflammation and innate immunity of cancer is more widely accepted today, many of the precise cell mechanisms mediating this relationship have not been elucidated. Th17 cells, which produce the proinflammatory cytokine interleukin 17 (IL-17), have been recognized as one of the key factors in the regulation of inflammatory bowel disease and rheumatoid arthritis. This study demonstrated that, in patients with various types of gastrointestinal cancer, IL-17 production was correlated with myeloid-derived suppressor cell (MDSC) levels and with markers for nutritional impairment, immune suppression and chronic inflammation. IL-17 was significantly higher in patients with various types of gastrointestinal cancer compared to normal volunteers. In addition, IL-17 levels were significantly correlated with neutrophil counts and the neutrophil/lymphocyte ratio (NLR) and significantly inversely correlated with cell-mediated immune response indicators [lymphocyte phytohemagglutinin (PHA)-blastogenesis and IL-12 induction] and patient nutritional status (prealbumin levels). Circulating MDSC levels were significantly correlated with IL-17 production. These results suggest that, in human gastrointestinal cancers, chronic inflammation involving IL-17 may be an important mechanism contributing to disease progression through enhancement of immune suppression or cachexia. Controlling the activation of Th17 cells may prove to be a valuable strategy for the treatment of gastrointestinal cancer patients.

Hepatocellular carcinoma that relapsed 54 months after living donor liver transplantation.

We report the case of a 41-year-old woman with hepatocellular carcinoma (HCC). She received living donor liver transplantation (LDLT) from her husband for HCC at 36 years of age. She had few risk factors for HCC recurrence, such as elevated alpha-fetoprotein (AFP), protein induced by vitamin K absence (PIVKA) II, vascular invasion, and number, size of tumors. However, recurrent tumors were found in the graft at 54 months after LDLT. Although we examined the sex chromosomes of the HCC by fluorescence in situ hybridization (FISH) methods, the origin of the HCC was unclear. This is a very rare case of recurrent HCC appearing more than 4 years after LDLT in the absence of risk factors for recurrence.

Phase I trial of preoperative intratumoral injection of immature dendritic cells and OK-432 for resectable pancreatic cancer patients.

PURPOSE: To determine the feasibility, safety and histological change of preoperative endoscopic ultrasound-guided fine-needle injection (PEU-FNI) of immature DCs (iDCs) with OK-432 in pancreatic cancer patients. METHODS: Nine patients enrolled in the trial (DC group) and were compared with 15 patients operated on without iDC injection (non-DC group). Adverse events of PEU-FNI and postoperative complications were evaluated according to CTC-AE ver.3.0 and the Clavien-Dindo classification/ISGPF definition, respectively. Histological changes within the tumor and lymph nodes were evaluated by immunohistochemical examination of infiltrating inflammatory cells (CD4+, CD8+, Foxp3+ and CD83+). RESULTS: There were no severe toxicities following PEU-FNI, except for one transient grade 3 fever, and there were no significant differences in the incidence of postoperative complications between the two groups. Colliquative necrosis and diffusely scattered TUNEL-positive cells were observed at the injection sites. CD83+ cells significantly accumulated in the regional lymph nodes of the DC group as well as Foxp3+ cells in the regional and distant lymph nodes. The two DC group patients, one of which was stage IV with distant lymph node metastasis, survived more than 5 years without requiring adjuvant theraphy. CONCLUSION: PEU-FNI was feasible and safe, and further study needs to confirm and enhance antitumor responses.

Improved islet yield and function by use of a chloride channel blocker during collagenase digestion.

BACKGROUND: Protection of pancreatic islets during isolation procedures is mandatory for successful islet transplantation. Chloride channel inhibition has been reported to prevent cell death induced by various stimuli. We examined the effects of the chloride channel blocker, 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid disodium salt (DIDS) and extracellular Cl(-)-free conditions on islet isolation outcomes. METHODS: Experimental groups were created based on the collagenase solutions used for Wistar rat islet isolation: control group, Hanks' balanced salt solution; DIDS group, 200 µM DIDS; and Cl(-)-free group, sodium gluconate substituted for sodium chloride. We determined whether collagenase digestion induced the death of islet cells through Cl(-) influx into the cells. We then assessed islet yield and the viability of isolated islets. RESULTS: We observed an increase in intracellular Cl(-) concentration under collagenase digestion conditions using a Cl(-)-sensitive fluorescent dye and subsequent rupture of islet cells. Consequently, islet yields were significantly higher in the DIDS and Cl(-)-free groups than in the control group, and islet morphology of the former groups was preserved. Of streptozotocin-induced diabetic severe combined immunodeficiency mice transplanted with a marginal dose of islets, all seven mice in the DIDS group and six of the seven mice in the Cl(-)-free group became normoglycemic, compared with two of seven mice in the control group (control vs. DIDS, P=0.010; control vs. Cl(-) free, P=0.051). CONCLUSION: Our results indicate that DIDS inhibition of Cl(-) influx into islets protects islets during digestion procedures, offering a new strategy for the improvement of islet isolation outcomes.

Gene expression analysis for predicting gemcitabine resistance in human cholangiocarcinoma.

BACKGROUND: Gemcitabine is a promising drug for cholangiocarcinoma treatment. However, the kinetics and metabolism of this drug in cholangiocarcinoma treatment are not well defined. We aimed to investigate the potential clinical role of gemcitabine metabolism-related genes in the gemcitabine sensitivity of cholangiocarcinoma and identify and characterize novel gemcitabine resistance-related genes. METHODS: Expressions of genes related to gemcitabine sensitivity and gemcitabine metabolism were measured in 10 cholangiocarcinoma cell lines, and the association between gene expression and gemcitabine sensitivity was evaluated. Furthermore, gemcitabine-resistant cell lines were established from YSCCC cells and subjected to genome-wide microarray analysis. The 2-fold upregulated and downregulated genes were then subjected to pathway analysis. RESULTS: p53R2 mRNA expression was significantly higher in gemcitabine-resistant cell lines (IC(50) > 1000 nM), and all subunits of ribonucleotide reductase were upregulated in the established gemcitabine-resistant cell lines. Microarray analysis revealed that the upregulated genes in the resistant cells belonged to the glutathione and pyrimidine metabolism pathways, and that the downregulated genes belonged to the N-glycan biosynthesis pathway. CONCLUSIONS: Increased expression of p53R2 may predict gemcitabine resistance, and upregulated RNR activity may influence gemcitabine resistance in cholangiocarcinoma cells. Glutathione pathway-related genes were induced by continuous exposure to gemcitabine and may contribute to gemcitabine resistance.