Adaptive Dynamics Simulation of Interference Phenomenon for Physical and Biological Systems.

Biological systems have been shown to have quantum-like behaviors by applying the adaptive dynamics view on their interaction networks. In particular, in the process of lactose-glucose metabolism, cells generate probabilistic interference patterns similarly to photons in the two-slit experiment. Such quantum-like interference patterns can be found in biological data, on all scales, from proteins to cognitive, ecological, and social systems. The adaptive dynamics approach covers both biological and physical phenomena, including the ones which are typically associated with quantum physics. We guess that the adaptive dynamics can be used for the clarification of quantum foundations, and the present paper is the first step in this direction. We suggest the use of an algorithm for the numerical simulation of the behavior of a billiard ball-like particle passing through two slits by explicitly considering the influence of the two-slit environment (experimental context). Our simulation successfully mimics the interference pattern obtained experimentally in quantum physics. The interference of photons or electrons by two slits is known as a typical quantum mechanical effect. We do not claim that the adaptive dynamics can reproduce the whole body of quantum mechanics, but we hope that this numerical simulation example will stimulate further extensive studies in this direction-the representation of quantum physical phenomena in an adaptive dynamical framework.

Acute peritonitis caused by the acute pancreatitis of an ectopic pancreas in a jejunal duplication, in an adult with intestinal malrotation: a case report.

BACKGROUND: Intestinal duplication and ectopic pancreas are two rare independent congenital anomalies. Few reports describe cases of patients with ectopic pancreas in an intestinal duplication causing acute peritonitis. CASE PRESENTATION: A 31-year-old man was admitted to the hospital for epigastric pain. The patient was diagnosed with acute peritonitis caused by the acute pancreatitis of an ectopic pancreas in a jejunal duplication, with intestinal malrotation. The patient underwent the partial resection of the jejunum and Ladd's procedure. The histopathological findings indicated ectopic pancreatitis in the jejunal duplication. CONCLUSIONS: We presented the case of acute peritonitis caused by the acute pancreatitis of an ectopic pancreas in a jejunal duplication in an adult with intestinal malrotation. Surgery is the primary treatment and is necessary for a definitive diagnosis.

Giant splenic artery aneurysm rupture into the stomach that was successfully managed with emergency distal pancreatectomy.

BACKGROUND: Splenic artery aneurysms usually rupture into the free peritoneal space and rarely into the gastrointestinal tract. We report the case of a patient with a giant splenic artery aneurysm that ruptured in to the stomach with hemorrhagic shock and was successfully treated with emergency surgery. CASE PRESENTATION: A 59-year-old man presented to the emergency department with chest pain and syncope. Contrast-enhanced computed tomography showed splenic artery aneurysm with active contrast extravasation. He developed upper gastrointestinal (UGI) bleeding and hypovolemic shock. We diagnosed a splenic artery aneurysm ruptured in to the stomach, performed emergency distal splenopancreatectomy including the aneurysm and partial gastric resection, and could prevent patient death. CONCLUSIONS: This report shows that splenic artery aneurysm can cause UGI bleeding. Thus, clinicians should be alert about this condition when managing patients with UGI bleeding and/or splenic artery aneurysm.

An affinity change model to elucidate the rotation mechanism of V1-ATPase.

V-ATPases are ubiquitous proton-transporting ATPases of eukaryotic and prokaryotic membranes that utilize energy from ATP hydrolysis. The hydrophilic catalytic part called V1-ATPase is composed of a ring-shaped hexametric A3B3 complex and a central DF shaft. We previously proposed a rotation mechanism of the Enterococcus hirae V1-ATPase based on the crystal structures of the V1 and A3B3 complexes. However, the driving force that induces the conformational changes of A3B3 and rotation of the DF shaft remains unclear. In this study, we investigated the binding affinity changes between subunits of V1-ATPase by surface plasmon resonance analysis. The binding of ATP to subunit A was found to considerably increase the affinity between the A and B subunits, and thereby ATP binding contributes to forming the A1B1 tight conformation. Furthermore, the DF shaft bound to the reconstituted A1B1 complex with high affinity, suggesting that the tight A1B1 complex is a major binding unit of the shaft in the A3B3 ring complex. Based on these results, we propose that rotation of the V1-ATPase is driven by affinity changes between each subunit via thermal fluctuations.

Metastable asymmetrical structure of a shaftless V1 motor.

V1-ATPase is an ATP-driven rotary motor that is composed of a ring-shaped A3B3 complex and a central DF shaft. The nucleotide-free A3B3 complex of Enterococcus hirae, composed of three identical A1B1 heterodimers, showed a unique asymmetrical structure, probably due to the strong binding of the N-terminal barrel domain, which forms a crown structure. Here, we mutated the barrel region to weaken the crown, and performed structural analyses using high-speed atomic force microscopy and x-ray crystallography of the mutant A3B3. The nucleotide-free mutant A3B3 complex had a more symmetrical open structure than the wild type. Binding of nucleotides produced a closely packed spiral-like structure with a disrupted crown. These findings suggest that wild-type A3B3 forms a metastable (stressed) asymmetric structure composed of unstable A1B1 conformers due to the strong constraint of the crown. The results further the understanding of the principle of the cooperative transition mechanism of rotary motors.

Rotational Mechanism Model of the Bacterial V1 Motor Based on Structural and Computational Analyses.

V1-ATPase exemplifies the ubiquitous rotary motor, in which a central shaft DF complex rotates inside a hexagonally arranged catalytic A3B3 complex, powered by the energy from ATP hydrolysis. We have recently reported a number of crystal structures of the Enterococcus hirae A3B3DF (V1) complex corresponding to its nucleotide-bound intermediate states, namely the forms waiting for ATP hydrolysis (denoted as catalytic dwell), ATP binding (ATP-binding dwell), and ADP release (ADP-release dwell) along the rotatory catalytic cycle of ATPase. Furthermore, we have performed microsecond-scale molecular dynamics simulations and free-energy calculations to investigate the conformational transitions between these intermediate states and to probe the long-time dynamics of the molecular motor. In this article, the molecular structure and dynamics of the V1-ATPase are reviewed to bring forth a unified model of the motor's remarkable rotational mechanism.

Quantum probability in decision making from quantum information representation of neuronal states.

The recent wave of interest to modeling the process of decision making with the aid of the quantum formalism gives rise to the following question: 'How can neurons generate quantum-like statistical data?' (There is a plenty of such data in cognitive psychology and social science). Our model is based on quantum-like representation of uncertainty in generation of action potentials. This uncertainty is a consequence of complexity of electrochemical processes in the brain; in particular, uncertainty of triggering an action potential by the membrane potential. Quantum information state spaces can be considered as extensions of classical information spaces corresponding to neural codes; e.g., 0/1, quiescent/firing neural code. The key point is that processing of information by the brain involves superpositions of such states. Another key point is that a neuronal group performing some psychological function F is an open quantum system. It interacts with the surrounding electrochemical environment. The process of decision making is described as decoherence in the basis of eigenstates of F. A decision state is a steady state. This is a linear representation of complex nonlinear dynamics of electrochemical states. Linearity guarantees exponentially fast convergence to the decision state.

A model of differentiation in quantum bioinformatics.

Differentiation is a universal process found in various phenomena of nature. As seen in the example of cell differentiation, the creation diversity on individual's character is caused by environmental interactions. In this paper, we try to explain its mechanism, which has been discussed mainly in Biology, by using the formalism of quantum physics. Our approach known as quantum bioinformatics shows that the temporal change of statistical state called decoherence fits to describe non-local phenomena like differentiation.

Energy and information flows in biological systems: Bioenergy transduction of V1-ATPase rotary motor and dynamics of thermodynamic entropy in information flows.

We classify research fields in biology with respect to flows of materials, energy, and information. We investigate energy transducing mechanisms in biology, using as a representative the typical molecular rotary motor V1-ATPase from a bacterium Enterococcus hirae. The structures of several intermediates of the rotary motor are described and the molecular mechanism of the motor converting chemical energy into mechanical energy is discussed. Comments and considerations on the information flows in biology, especially on the thermodynamic entropy in quantum physical and biological systems, are presented in section 3 in a biologist friendly manner.

Rotation Mechanism of Molecular Motor V1-ATPase Studied by Multiscale Molecular Dynamics Simulation.

Enterococcus hirae V1-ATPase is a molecular motor composed of the A3B3 hexamer ring and the central stalk. In association with ATP hydrolysis, three catalytic AB pairs in the A3B3 ring undergo conformational changes, which lead to a 120° rotation of the central stalk. To understand how the conformational changes of three catalytic pairs induce the 120° rotation of the central stalk, we performed multiscale molecular dynamics (MD) simulations in which coarse-grained and all-atom MD simulations were combined using a fluctuation matching methodology. During the rotation, a catalytic AB pair spontaneously adopted an intermediate conformation, which was not included in the initial inputs of the simulations and was essentially close to the "bindable-like" structure observed in a recently solved crystal structure. Furthermore, the creation of a space between the bindable-like and tight pairs was required for the central stalk to rotate without steric hindrance. These cooperative rearrangements of the three catalytic pairs are crucial for the rotation of the central stalk.

Intraarterial Therapy Using Micellar Nanoparticles Incorporating SN-38 in a Rabbit Liver Tumor Model.

PURPOSE: To evaluate the pharmacokinetics of intraarterial (IA) administration of micellar nanoparticles incorporating SN-38 injection compared with intravenous (IV) administration in a rabbit liver tumor model. MATERIALS AND METHODS: In this animal care committee-approved study, 18 rabbits (mean weight, 3.89 kg; range, 3.20-4.70 kg) with VX2 liver tumors were divided into two groups (IA and IV). Micellar nanoparticles incorporating SN-38 (30 mg/kg) were injected through the left hepatic artery in the IA group and the right femoral vein in the IV group. NK012 and free SN-38 in the plasma, liver parenchyma, and tumors were measured within 24 hours. Histologic examinations were conducted at 2 and 24 hours. RESULTS: There were no significant differences in the serum area under the concentration-time curve (0-24 h) for free SN-38, at 1,500 and 1,310 µg∙min/mL in the IA and IV groups, respectively (P = .152). The IA group showed significantly higher free SN-38 concentrations in tumor tissues at all time points compared with the IV group (P = .002 at 3 min, P = .011 at 2 h, and P = .047 at 24 h). Histologic findings showed that significantly higher tumor necrosis ratios were observed in the IA group compared with the IV group at 24 hours (P = .028). CONCLUSIONS: Micellar nanoparticles could be a promising IA drug delivery system to achieve high tumor tissue concentrations of SN-38.

The Administration of Celecoxib as an Analgesic after Liver Resection Is Safe.

BACKGROUND: There are a few studies that have evaluated postoperative analgesia. The aim of this study was to evaluate the safety of administering celecoxib to manage postoperative pain after liver surgery. METHODS: The cases of patients who underwent liver resection at Nara Medical University from April 2008 to December 2015 were retrospectively analyzed. From January 2013 to December 2015, celecoxib was routinely administered (600 mg/day on postoperative day (POD) 2 and 400 mg/day from POD 3-7), whereas celecoxib was not administered from April 2008 to December 2012. The patients' baseline characteristics, the operative procedures, and postoperative complications were analyzed. RESULTS: In total, 207 patients were administered celecoxib (celecoxib group), whereas 246 were not (non-celecoxib group). The preoperative serum total bilirubin and creatinine levels and indocyanine green retention rate at 15 min values of the 2 groups were similar. Similar incidences of overall and major complications (Clavien-Dindo classification ≥grade IIIa) were seen in both groups (33.8 vs. 36.2%, p = 0.601 and 12.1 vs. 12.6%, p = 0.866, respectively). No significant differences in the incidences of gastrointestinal bleeding, acute renal failure, or portal vein thrombosis were observed between the groups. CONCLUSIONS: The use of celecoxib for postoperative analgesia in the early period after liver resection is safe.

Pharmacokinetics and Histopathological Findings of Chemoembolization Using Cisplatin Powder Mixed with Degradable Starch Microspheres in a Rabbit Liver Tumor Model.

PURPOSE: The purpose of this study is to evaluate the pharmacokinetics and histopathological findings of transarterial chemoembolization (TACE) using cisplatin powder mixed with degradable starch microspheres (DSM) (Cis/DSM-TACE) compared with cisplatin arterial infusion (Cis-AI). MATERIALS AND METHODS: Eighteen rabbits with VX2 liver tumors were divided into two groups: Cis/DSM-TACE (n = 9) and Cis-AI (n = 9) groups. In the Cis/DSM-TACE group, a mixture of cisplatin powder and DSM was injected until stasis of hepatic arterial flow was achieved. In the Cis-AI group, cisplatin solution was infused. RESULTS: The platinum concentrations in VX2 tumors in the Cis/DSM-TACE group at 24 and 72 h were significantly elevated compared with those in the Cis-AI group (P = .016 and .019, respectively). There were no significant differences in the platinum concentrations in plasma. Histopathological examination revealed the presence of several microspheres inside the tumors at 1 h, which completely disappeared at 24 h. Tumor cell apoptosis at 1 h in the Cis/DSM-TACE group was more frequently observed compared with that in the Cis-AI group (P = .006). CONCLUSIONS: TACE using cisplatin powder mixed with DSM provides a higher drug concentration in tumors, thereby achieving stronger antitumor effects compared with arterial infusion of cisplatin solution.

Operating principles of rotary molecular motors: differences between F1 and V1 motors.

Among the many types of bioenergy-transducing machineries, F- and V-ATPases are unique bio- and nano-molecular rotary motors. The rotational catalysis of F1-ATPase has been investigated in detail, and molecular mechanisms have been proposed based on the crystal structures of the complex and on extensive single-molecule rotational observations. Recently, we obtained crystal structures of bacterial V1-ATPase (A3B3 and A3B3DF complexes) in the presence and absence of nucleotides. Based on these new structures, we present a novel model for the rotational catalysis mechanism of V1-ATPase, which is different from that of F1-ATPases.

Crystal structures of the ATP-binding and ADP-release dwells of the V1 rotary motor.

V1-ATPases are highly conserved ATP-driven rotary molecular motors found in various membrane systems. We recently reported the crystal structures for the Enterococcus hirae A3B3DF (V1) complex, corresponding to the catalytic dwell state waiting for ATP hydrolysis. Here we present the crystal structures for two other dwell states obtained by soaking nucleotide-free V1 crystals in ADP. In the presence of 20 µM ADP, two ADP molecules bind to two of three binding sites and cooperatively induce conformational changes of the third site to an ATP-binding mode, corresponding to the ATP-binding dwell. In the presence of 2 mM ADP, all nucleotide-binding sites are occupied by ADP to induce conformational changes corresponding to the ADP-release dwell. Based on these and previous findings, we propose a V1-ATPase rotational mechanism model.

The prognosis of liver resection for patients with four or more colorectal liver metastases has not improved in the era of modern chemotherapy.

BACKGROUND AND OBJECTIVES: The impact of perioperative chemotherapy on patients with multiple colorectal liver metastases (CRLM) remains unclear. We attempted to examine whether the introduction of modern chemotherapies has improved the prognosis of patients that undergo liver resection for ≥4 CRLM. METHODS: Between January 1990 and December 2013, 194 patients underwent liver resection for CRLM at our institution. The outcomes of the patients with ≥4 and 1-3 CRLM were compared before and after 2005, when modern chemotherapies were introduced to Japan. RESULTS: There were 50 and 144 patients with ≥4 (Group 1) and 1-3 (Group 2) CRLM, respectively. The overall survival (OS) rate of Group 1 was significantly worse than that of Group 2 (P = 0.0007). The OS rate of Group 2 was significantly better after 2005 than before 2004 (P = 0.039), while no such differences were observed in Group 1. Multivariate analysis identified three prognostic factors in Group 1: a serum carcinoembryonic antigen level of ≥20 ng/ml (P = 0.018), a serum cancer antigen 19-9 level of ≥100 U/ml (P = 0.018), and a primary colorectal cancer N factor of ≥N2 (P = 0.023). CONCLUSIONS: The prognosis of patients with ≥4 CRLM that undergo liver resection has not improved despite the development of modern chemotherapies. J. Surg. Oncol. 2016;114:959-965. © 2016 Wiley Periodicals, Inc.

Laparoscopic resection of a hepatic mucinous cystic neoplasm: A case report.

INTRODUCTION: We aimed to present a case of hepatic mucinous cystic neoplasm (MCN-H) that was completely resected by laparoscopy. PRESENTATION OF CASE: A 47-year-old female exhibited mild elevation of serum liver enzyme levels. Abdominal computed tomography revealed a 45-mm multilocular cystic tumor in segment IV of the liver, along with intermittent border calcification and minimal wall thickness. Magnetic resonance imaging revealed fluid-to-fluid level in the cystic tumor, thereby increasing the suspicion of a mild hemorrhage. The patient underwent laparoscopic liver resection (LLR) with a diagnosis of suspected mucinous cystic neoplasm of the liver. The entire tumor was successfully resected with a laparoscopic approach. The resected specimen was a 4.2×3.3×2.2-cm cystic tumor. Histological findings revealed mucin-producing singular epithelium and ovarian-like stroma. The tumor was diagnosed as a MCN-H with no malignancy. DISCUSSION: This is the first report in which a MCN-H was completely resected by laparoscopy. MCN-H is rare and is observed in only<5% of liver cystic tumors. MCN-H has been reported to have the malignant potential. And complete resection might be a good treatment option. Along with technical development, LLR has been indicated for benign liver tumors to date. Benign liver tumors are commonly observed in young females. The smaller incisions of the laparoscopic approach might provide cosmetic advantages for patients. CONCLUSION: We presented the first case of a MCN-H completely resected by laparoscopy. Benign tumors and tumors with malignant potential might be good indications for a laparoscopic surgery.

Three-body system metaphor for the two-slit experiment and Escherichia coli lactose-glucose metabolism.

We compare the contextual probabilistic structures of the seminal two-slit experiment (quantum interference experiment), the system of three interacting bodies andEscherichia colilactose-glucose metabolism. We show that they have the same non-Kolmogorov probabilistic structure resulting from multi-contextuality. There are plenty of statistical data with non-Kolmogorov features; in particular, the probabilistic behaviour of neither quantum nor biological systems can be described classically. Biological systems (even cells and proteins) are macroscopic systems and one may try to present a more detailed model of interactions in such systems that lead to quantum-like probabilistic behaviour. The system of interactions between three bodies is one of the simplest metaphoric examples for such interactions. By proceeding further in this way (by playing withn-body systems) we shall be able to find metaphoric mechanical models for complex bio-interactions, e.g. signalling between cells, leading to non-Kolmogorov probabilistic data.