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Mathematical modeling of the fermentation process is useful for understanding the influence of operating parameters on target production and control performance, depending on the situation, to stabilize the target production at a high-level. However, the previous approaches using physical modeling methods and traditional knowledge-based methods are difficult to apply on working fermentors at a commercial plant scale because they have unknown and unmeasured parameters involved in target production. This study focused on developing an ensemble learning model that can predict the amino acid fermentation process behavior based on observation values, which can be obtained from fermentation tanks and future control input. The results revealed the influence of each control input on lysine production during the culturing period. Furthermore, high-order stability, which achieved the target trajectory for lysine production, was realized using dynamic fermentation controls. Additionally, this study demonstrates that the fermentation behavior on a commercial plant scale is reproduced using the ensemble device. The ensemble learning model will provide novel control system with data-science based model of Industry 4.0 in the field of biotechnological processes.

Monitoring cell growth and target production in working fermentors is important for stabilizing high level production. In this study, we developed a novel soft sensor for estimating the concentration of a target product (lysine), substrate (sucrose), and bacterial cell in commercially working fermentors using machine learning combined with available on-line process data. The lysine concentration was accurately estimated in both linear and nonlinear models; however, the nonlinear models were also suitable for estimating the concentrations of sucrose and bacterial cells. Data enhancement by time interpolation improved the model prediction accuracy and eliminated unnecessary fluctuations. Furthermore, the soft sensor developed based on the dataset of the same process parameters in multiple fermentor tanks successfully estimated the fermentation behavior of each tank. Machine learning-based soft sensors may represent a novel monitoring system for digital transformation in the field of biotechnological processes.

Fracture tests and finite element analysis were conducted to evaluate the temperature dependence of the effective surface energy γ mm corresponding to microcrack propagation across the grain boundary of steels. Steels containing coarse cementite particles were prepared to enable γ mm evaluation. The critical fracture stress of microcrack propagation across the grain boundary is considered larger than the critical fracture stress of microcrack propagation across the interface between a cementite particle and a ferrite grain in these steels because of the large cementite particles; therefore, local fracture stress estimated by finite element analysis and fracture initiation site obtained by fractography reflect the critical fracture stress of microcrack propagation across the grain boundary. Thus, the accuracy of γ mm calculated from local fracture stress is observed to be enhanced by employing the steels prepared for the present study. In addition, the effect of nickel on γ mm was studied using steels containing different concentrations of nickel. Values of γ mm were evaluated considering both the direction of a neighboring facet relative to the crack initiation facet and the mixed mode stress intensity factors. The authors proposed a new temperature dependence of γ mm . Additionally, the negligible effect of nickel addition on γ mm was observed. The results of the present study can be used effectively to develop a probabilistic cleavage fracture model based on microstructural information.

We developed the first model to evaluate unstable ductile crack arrestability in offshore pipelines. The proposed model is an integrated one-dimensional model with four sub-models to calculate (a) pipe deformation, (b) gas flow inside pipe, (c) bubble growth, and (d) crack propagation. We validated the proposed model by applying it to two types of tests: laboratory scale underwater rupture tests and existing data of a full-scale burst test of an offshore pipeline. In addition, the calculation results of the proposed model showed that a deep water depth results in increased unstable crack arrestability of the pipeline.

Prevention of unstable ductile crack propagation has been a great issue in pipeline industry. For appropriate pipe design, the authors developed a numerical model to predict unstable ductile crack propagation/arrest using finite difference method. The features of the model are as follows: (1) pipe deformation and gas decompression are formulated based on one-dimensional partial differential equations; (2) the interaction among pipe deformation, gas decompression and crack propagation is considered; (3) soil backfill effect, which constrains pipe deformation, is considered as added density. In this paper, the model is described in detail, and applied to full-scale natural gas pipe burst tests.

In this research, atmospheric and underwater small-scale pipe rupture disk tests were conducted. Tested pipes with rupture disk were pressurized by pure nitrogen, in which internal pressure changes and external pressure changes were measured by pressure transducers. By comparing results of the underwater tests with results of the atmospheric tests, water effects were clarified: (1) gas decompression in the underwater tests delays due to constrained gas leak by bubble generation and growth as compared to gas decompression in the atmospheric tests, and (2) larger external pressure changes were measured in the underwater tests. In addition, 1D finite-difference based coupled model for gas decompression, in which gas flow inside a pipe and bubble growth are considered, was developed. In the model, governing equations for gas flow inside a pipe and a bubble are derived from mass conservation law and momentum conservation law assuming isentropic changes of gas. Bubble growth is formulated based on Rayleigh-Plesset equation. The calculated results for the rupture disk tests using the model showed good agreements with the experimental results, which analytically clarified the above stated water effects. This research reveals an importance of considering the water effects in evaluating fractures in offshore pipelines. In the future, it is expected that the model is extended to incorporate crack propagation and pipe deformation together with gas decompression and bubble growth.

Intramural duodenal haematoma (IDH) is a rare condition forming haematoma within the wall of the duodenum, which was first reported in 1838 by MacLauchlan.1 IDH derived from acute or chronic pancreatitis is rarely described, the mechanism remaining unknown. A 65-year-old man with history of heavy drinking and chronic hepatitis was admitted to our hospital with sudden vomiting and right-lateral abdominal pain. Abdominal pain and vomiting continued after admission, so a nasogastric tube was inserted. Contrast-enhanced CT scans of the abdomen found a 60×80 mm heterogeneous mass with intraluminal leakage of contrast agent-like bleeding along the second portion of the duodenum, diffuse expansion of the pancreatic duct with pancreatic stone and ascites on the surface of the liver (figure 1). We first considered whether …

Critical CTOD is widely used as a fracture toughness parameter for structural steels. Critical CTOD often has a scatter of more than one order of magnitude. To explain this scatter, Beremin proposed a model called Weibull stress or Beremin model, but some researches cast doubts on the model. Some models were proposed so that they consider microcrack nucleation by taking plastic strain into account. However, these models cannot completely describe experiments, nor did they calculate the scatter of fracture initiation points. The aim of the present paper is to propose a new model which more precisely predict fracture toughnesses as well as fracture initiation points.

In the present study, three-dimensional cleavage crack path prediction model is proposed. The model is based on the local fracture stress criterion in which three candidates for a cleavage plane in a computational element is assumed and the one which has maximum value of normal stress divided by local fracture stress is selected. In this model, normal stress acting on each plane is obtained by local stress intensity factor which is calculated by combination of approximate solutions where crack front non-straightness, crack surface irregularity and crack closing force acting at ridges between crack planes are considered. The model also incorporates multiaxial stress field and non-uniform toughness distribution. Therefore, this model is applied to welded joint of ESSO test where welding residual stress and non-uniform toughness distribution exist, and the predicted results of crack paths show a general agreement with the test results. Parametric study is also conducted in order to discuss the effects of applied stress, welding residual stress, toughness distribution and type of welding groove on brittle crack path behavior.

症例は63歳の女性で，閉塞性黄疸で当院に入院となった．黄疸は保存的治療にて軽快するも，腹部CTで肝側の胆嚢内に淡く造影効果を受ける45×50 mmの乳頭型腫瘍とNo.12c，No.13aに著明に腫大したリンパ節を認め，胆嚢癌の診断で手術を施行した．膵頭部領域のリンパ節は膵実質との線維性癒着のみで剥離が容易であった．胆嚢床切徐を伴う胆嚢摘出術，肝外胆管切徐とD2リンパ節郭清，肝管空腸吻合術を施行した．胆嚢内には多量の粘液を認め，病理組織学的には，pap，mp，medullary type，INFα，ly0，v0，pn0，pHinf0，pBinf0，pPV0，pA0，pBM0，pHM0，pEM0，n2（＋），（2/13，No12c，13a），fStageIIIであった．消長した閉塞性黄疸は産生された粘液によるものと考えた．粘液産生胆嚢癌はまれであり，文献的考察を加えて報告する．

n° spécial Full-field Measurements in Composites Testing and Analysis; International audience; Meso-scale (unit cell of an impregnated textile reinforcement) finite element (FE) modelling of textile composites is a powerful tool for homogenisation of mechanical properties, study of stress–strain fields inside the unit cell, determination of damage initiation conditions and sites and simulation of damage development and associated deterioration of the homogenised mechanical properties of the composite. Validation of meso-FE modelling requires registration of details of the deformed state on the scale of individual yarns inside the textile, registered using full-field strain measurements on the surface of the sample. The paper presents examples of such a validation of meso-FE models of woven (carbon/epoxy and glass/polypropylene) and braided (carbon/epoxy) composites. Digital image correlation and digital phase shifting grating shearography are used for full-field strain registration. The resolution of the strain field during elastic deformation is improved and damage onset is identified using time-dependent linear regression of the registered field.

We developed an image recognition processor, “Visconti,” based on a configurable processor. Three VLIW processors that execute three instructions in parallel are integrated into a single chip with peripheral modules such as video I/Os and an SDRAM controller. Each VLIW processor has a RISC processor core and a VLIW coprocessor dedicated to image processing. The coprocessor executes SIMD instructions such as 8-parallel byte. Visconti was fabricated using 0.13μm CMOS technology, operates at 150MHz, and consumes about 1W. We present actual application examples of Visconti, onboard surveillance for automobiles and face recognition. Compared to cases in which only the processor core is used, execution speed per one processor increases about 16 times for onboard surveillance and about five times per three processors for face recognition. These applications can be processed in real time.

A service load like random load has been analyzed by the rain flow method extensively. When the reliability of a structure is estimated, mean stresses on fatigue life are probably ignored because it is not easy to measure. The purpose of this study is to propose a practical estimation method of a structural reliability for fatigue under service loads by Miner's law. In addition, the fatigue tests to obtain S-N curve is carried out under constant amplitude loading. However, the each stress ratio of cyclic stress counted with rain flow method is different. In the proposed method, the effect of stress ratio has been considered by fatigue limit diagram with failure probability. On this diagram, the increment of cumulative cycle ratio ΔDpf for each cyclic stress can be calculated with failure probability by a computer program. The expected life Npf is defined as the period when Dpf reaches 1.0. If we assume the ergodicity of the sampling time T, Npf is T/Dpf. It gives fatigue life distribution, when a structure is under service loads. In conclusion, we have got a reliability curve of the structure for fatigue life. This curve can be obtained with service load or design stress easily by using our developed program. This proposed method is practical and the industrial applicability is wide.

It is very important for the damage tolerance design of a structure to reveal the behavior of fatigue cracks of the used material. They have some uncertainties, the random applied loads or the residual strength caused by manufacturing process and so on. It is difficult to evaluate the behaviors of real fatigue cracks. In this paper, an evaluation method for fatigue life based on fatigue crack length has been proposed. Fokker-Planck equation, which can describe fatigue crack propagation under random load and random propagation resistance, has been proposed. The distribution of fatigue life has been analyzed by combining both of the distribution of crack initiation life and the distribution of propagation life.

Diaphragms made of a stainless steel plates are widely used as switching parts in electronic devices. Due to the cyclic loading applied to these diaphragms, the estimation of the lives of diaphragms is important to decide that of the electronic devices. The fatigue characteristic of the diaphragm must be discussed with considering the large scatter of material properties induced by the anisotropy. In this study, the tensile and the fatigue tests have been carried out some specimens with a direction to cold rolling direction. A pulley driving system was adopted as a fatigue testing apparatus because the load can be easily applied even when the thickness of the specimen is less than 0.1mm. From the experimental results, we have decided the S-N curve by applying large scatter of fatigue lives to the probability distribution based on reliability, and drew the Goodman diagram to avoid the effect of the mean stress. The obtained results can be used for fatigue design considering the anisotropy in the case of high cycle fatigue for diaphragms.

Fatigue characteristics of a metal diaphragm in a light touch switch are evaluated with experimental approach considering a cyclic load acting on it. The approach consumes much time and costs for evaluation. In previous paper, we have described that the mechanical properties of stainless steel have anisotropy and the fatigue characteristic must be discussed with considering the large scatter of material properties induced by the anisotropy. Therefore, the purpose of this study is to establish a simple method to evaluate the reliability of diaphragms with the consideration of anisotropy. The proposed approach consists of three procedures. Firstly, residual stress after press forming is evaluated by FEM, and feeling curves when the pushing load by is applied on the diaphragm are also analyzed. And, the stress amplitude and the mean stress at every point on the diaphragm can be calculated. Secondly, the experimental database about S-N curve and Goodman diagram considering the effect of anisotropy have been prepared. Finally, the fatigue lives considering failure probability on the diaphragm can be estimated by comparison of Goodman diagram and numerical results. From the obtained results, it is revealed that the proposed approach is very useful for the reliability evaluation of the diaphragm.

Diaphragms made of stainless steel plates are widely used as switching parts in electrical devices. Since the cyclic loading is applied to these diaphragms by the repeated switching mode of on/off, the estimation of the fatigue life of diaphragms is very important. The fatigue characteristics of the diaphragm must be discussed considering the large scatter of material properties induced by the anisotropy. In this study, the tensile and the fatigue tests have been carried out for some specimens with a direction to cold rolling direction. A pulley driving system has been adopted as a fatigue testing apparatus because the load can be applied even when the thickness of the specimen is less than 0.1mm. From the experiment, it is recognized that the experimental data is scattered largely. In addition, the residual stress is generated by a press forming process and the stress acts on the diaphragm as a mean stress. In order to estimate the reliability of a diaphragm, therefore, the Goodman diagram with a design margin which can be considered the mean stress for fatigue can be obtained. We have proposed the method which can evaluate the reliability of a diaphragm to design life by Goodman diagram.

Fatigue characteristics of a metal diaphragm in a light touch switch are evaluated with experimental approach considering cyclic load acting on it. The approach consumes much time and costs for evaluation. In previous paper, we have described that the mechanical properties of stainless steel have anisotropy and the fatigue characteristics must be discussed considering the large scatter of material properties induced by the anisotropy. Therefore, the purpose of this study is to establish a simple method to evaluate the reliability of diaphragms with the consideration of anisotropy. The proposed approach consists of three procedures. Firstly, residual stress after press forming is evaluated by finite element method (FEM), and response curves when the pushing load is applied on the diaphragm are also analyzed. And, the stress amplitude and the mean stress at every point on the diaphragm can be calculated. Secondly, the experimental database about S-N curve and Goodman diagram considering the effect of anisotropy have been prepared. Finally, the fatigue lives considering failure probabilities on the diaphragm can be estimated by comparison of Goodman diagram with numerical results. Obtained results revealed that the proposed approach is very useful for the reliability evaluation of the diaphragm.

Factor VIII (FVIII) inhibitor alloantibodies react with combinations of the A2, C2 and A3-C1 domains of the FVIII molecule. Some inhibitors block binding of FVIII to both von Willebrand factor (VWF) and phospholipid, and recognize a C2 domain epitope which overlaps both binding sites. In order to determine the essential binding regions for alloantibodies inhibitory for FVIII activity, we have performed inhibitor neutralization assays and competitive inhibition assays using 10 overlapping synthetic peptides spanning the carboxy-terminal region of the C2 domain (residues 2288–2332). We found one peptide (2315–2330, L9) which neutralized the anti-FVIII activity of four out of five different C2 alloantibodies by 50%, 39%, 47% and 57%, respectively. Neutralization of these alloantibodies by recombinant C2 domain (residues 2173–2332) was 68%, 50%, 59%, 86% and >95%, respectively. The inhibitor which was not neutralized by L9 peptide and reacted by immunoblotting with peptide 2218–2307, did not prevent binding of FVIII to VWF and only partially inhibited binding of FVIII to phosphatidylserine. Mutants of the L9 peptide were prepared in which each residue from 2315–2330 was sequentially substituted by glycine. Inhibitor neutralization experiments using these peptides demonstrated that Arg2320 and Cys2326 or Glu2327 are important for the effect of L9 peptide, since their substitution by glycine reduced its neutralizing effect by 60% to >90%, suggesting that they are crucial for formation of the one of the C2 inhibitor epitopes.

We have developed Visual Sensing System that monitors respiration for 24 hours non-restrictively. The principle of this system is inter-image subtraction. The gray scale levels of pixels on a ROI (region of interest) of a current frame are subtracted from those of a previous frame to make respiration patterns in time domain. Compared with conventional restrictive methods, this method is more convenient for long respiration monitoring since it does not restrain patients' bodies. In this paper, we explain some methods to enhance the system performance. We first explain methods that improve accuracy of detecting respiration patterns by setting a threshold and an interval for inter-image subtraction most adaptively. We then explain an authenticity judgement method that judges the authenticity of respiration patterns by comparing frequency characteristics of current periodic movements with those of normal respiration using Fast Fourier Transform and by comparing gray scale histograms of the current and the previous frames. We lastly explain an emergency message and a data sending method that sends emergency messages and respiration data to host computers using a socket function when abnormality in respiration is detected. Though the algorithms are simple, we achieved a high precision in extracting respiration patterns and also satisfied the needs of patients living at distant places.

Approximately 25% of hemophilia A patients infused with factor VIII (fVIII) mount an immune response, which leads to its inactivation. Anti-fVIII autoantibodies are also seen rarely in individuals with normal fVIII. We have previously demonstrated that some anti-A2 and anti-C2 domain antibodies are fVIII inhibitors and that many patients have additional inhibitors with a fVIII light chain (LCh) epitope outside C2. Because the contribution of the different antibodies to the plasma inhibitor titer had been examined in a limited number of patients (14), we report in this study a more extensive analysis of 55 plasmas. The dominant inhibitors in 62% (13 of 21) of autoantibody plasmas were directed only against C2 or A2, but not both, whereas this pattern was found in only 15% (5 of 34) of hemophilic plasmas. In addition, anti-A2 inhibitors were present in 71% (24 of 34) of hemophilic plasmas, but only 33% (7 of 21) of autoantibody plasmas. These results demonstrated that the inhibitor response in hemophiliacs was more complex and the epitope specificity was somewhat different. A comparison of hemophiliacs treated only with plasma fVIII or recombinant fVIII showed no significant differences in the complexity of the inhibitor response, as ≥ 2 different inhibitor antibodies were present in 78% (18 of 23) of the former and 82% (9 of 11) of the latter. In contrast, the major inhibitors in 35% (8 of 23) of hemophiliacs treated with plasma fVIII were directed against C2 and another LCh epitope within residues 1649-2137, but not A2, while none (0 of 11) treated with recombinant fVIII had this pattern.

Activated prothrombin complex concentrate (APCC), a by-passing hemostatic preparation for hemophilia A patients with a high titer of factor VIII inhibitors, often has an unpredictable hemostatic effect and occasionally results in severe thromboembolic complications. A clinical trial was conducted on 3 hemophilic patients with a high titer of factor VIII inhibitors to evaluate the safety and efficacy of a recombinant factor VIIa (rFVIIa; NN-007), an alternative by-passing preparaton. At the same time thrombelastgram (TEG) was evaluated to be better than activated-partial thromboplastin time (APTT) as a monitor of hemostatic effects when using rFVIIa. TEG was more suitable than APTT, because r, r+k and ma values of TEG were normalized at least for 4 hours after the infusion, whereas APTT was variably shortened and was not always maintained at a normal level for 4 hours. Sixty five μg/kg to 80μg/kg of rFVIIa was administered on demand once to 12 times per one bleeding episode. Eighty bleeding episodes were assessed during the 36-week treatment period. The efficacy rate of the hemostatic effect was confirmed to be 97.5%. No adverse reactions including laboratory or clinical DIC were observed in a total of 123 infusions. No anamnestic response of the factor VIII inhibitor developed. Vital signs and laboratory findings showed no significant changes attributable to rFVIIa. These findings suggest that rFVIIa is safe and efficacious as a by-passing hemostatic preparation for hemophilia A patients with a high titer of factor VIII inhibitors.

The rates of degradation of cyanuric acid, a key intermediate in a metabolic pathway of s-triazine herbicides, were measured for Pseudomonas sp. NRRL B-12227. The rate of degradation was affected by the rate of cyanuric acid transport through cell membranes and the activity of cyanuric acid amidohydrolase inside the cells. At low concentrations of cyanuric acid, the acclimation of cells to cyanuric acid and/or added nutrients effectively enhanced the degradation rate. The strain was also applied to bioremediation using a Bioremediation with Self-Immobilization System (BSIS), in which Pseudomonas sp. NRRL B-12227 cells were co-immobilized with Bacillus subtilis, the latter of which secretes a viscous polymer, in a shallow layer of soil packed in a column. More than 70% of the Pseudomonas sp. NRRL B-12227 cells were co-immobilized with the B. subtilis in a 7.5 cm layer of the packed soil by self-aggregation. More than 60% of the 1 mM cyanuric acid supplied to the packed soil was degraded in this layer during a 72 h period.

The A2 domain (residues 373-740) of human blood coagulation factor VIII (fVIII) contains a major epitope for inhibitory alloantibodies and autoantibodies. We took advantage of the differential reactivity of inhibitory antibodies with human and porcine fVIII and mapped a major determinant of the A2 epitope by using a series of active recombinant hybrid human/porcine fVIII molecules. Hybrids containing a substitution of porcine sequence at segment 410-508, 445-508, or 484-508 of the human A2 domain were not inhibited by a murine monoclonal antibody A2 inhibitory, mAb 413, whereas hybrids containing substitutions at 387-403, 387-444, and 387-468 were inhibited by mAb 413. This indicates that the segment bounded by Arg484 and Ile508 contains a major determinant of the A2 epitope. mAb 413 did not inhibit two more hybrids that contained porcine substitutions at residues 484-488 and 489-508, indicating that amino acid side chains on both sides of the Ser488-Arg489 bond within the Arg484-Ile508 segment contribute to the A2 epitope. The 484-508, 484-488, and 489-508 porcine substitution hybrids displayed decreased inhibition by A2 inhibitors from four patient plasmas, suggesting that there is little variation in the structure of the A2 epitope in the inhibitor population.

The authors propose a new model on cleavage fracture toughness of steels. Fracture toughness of steels is controlled by the weakest link mechanism, so it has intrinsic scatter. Beremin proposed Weibull stress through probabilistic fracture initiation model based on the weakest link theory, and it has been widely used for describing fracture toughness scatter. In his model, only propagation of micro crack is considered. However, micro crack nucleation should also be incorporated in order to estimate fracture toughness distribution more accurately. Bordet introduced micro crack initiation to the Beremin model, in which probability of micro crack nucleation is assumed proportional to plastic strain. Some previous studies have shown, however, that micro crack nucleation probability increases non-linearly with plastic strain. Then, we developed a new probabilistic model by introducing micro crack nucleation probability as a non-linear function of plastic strain. Furthermore, the authors developed a new method for obtaining Weibull parameters, in which not only distribution of fracture toughness values but also location of fracture initiation sites are considered through a newly developed likelihood function. We conducted fracture toughness tests with different specimen configurations and carried out convergence calculation for determining Weibull parameters by applying the likelihood function mentioned above. As a result of the calculation, the authors confirmed that the present model can obtain the Weibull parameters less sensitive to the specimen configurations and simulate distribution of fracture toughness more accurately than the previous models.

We isolated a highly transformable thermophile, Bacillus stearothermophilus SIC1, which exhibited the following features. The growth temperature ranged from 45 to 65°C in L broth. The maximum cell concentration in 2L broth (2% tryptone, 1% yeast extract, 0.5% NaCl, pH 7.2) was determined as an optical density at 660 nm of 7.8, and the generation time was 11 min at 60°C. Strain SIC1 was a prototroph and was transformed by the protoplast procedure not only with repB plasmids (high-copy-number plasmids such as pTB913 and pUB110) but also with repA plasmids (low-copy-number plasmids such as pTB53). Transformation efficiencies with repB and repA plasmids were about 2 × 10 6 to 5 × 10 6 and 5 × 10 4 transformants per μg of DNA, respectively. The transformant carrying plasmid pTB913Y/K could grow at 63°C in the presence of kanamycin. The regeneration frequency of protoplasts was 60%, and only 1 day was needed for regeneration at 55°C.