Integrated Metabolomics and Proteomics Analyses in the Local Milieu of Islet Allografts in Rejection versus Tolerance

An understanding of the immune mechanisms that lead to rejection versus tolerance of allogeneic pancreatic islet grafts is of paramount importance, as it facilitates the development of innovative methods to improve the transplant outcome. Here, we used our established intraocular islet transplant model to gain novel insight into changes in the local metabolome and proteome within the islet allograft’s immediate microenvironment in association with immune-mediated rejection or tolerance. We performed integrated metabolomics and proteomics analyses in aqueous humor samples representative of the graft’s microenvironment under each transplant outcome. The results showed that several free amino acids, small primary amines, and soluble proteins related to the Warburg effect were upregulated or downregulated in association with either outcome. In general, the observed shifts in the local metabolite and protein profiles in association with rejection were consistent with established pro-inflammatory metabolic pathways and those observed in association with tolerance were immune regulatory. Taken together, the current findings further support the potential of metabolic reprogramming of immune cells towards immune regulation through targeted pharmacological and dietary interventions against specific metabolic pathways that promote the Warburg effect to prevent the rejection of transplanted islets and promote their immune tolerance.     

Reliability design of structural system with cost effectiveness during life cycle

This study deals with an economic analysis of structural systems using a reliability-based design method. In this paper, a new expected total cost concept, which includes initial cost, cost of reliability test, annual maintenance cost, penalty cost for designer's faults and losses by structural failure is proposed. In the proposed formulation, the minimum expected total cost during the life duration with the capital rate of interest and rate of price fluctuations could be evaluated by calculating the present currency and annual prediction procedure.     

Trial of new intraocular lens power calculation following phototherapeutic keratectomy]

Thirty-one men (age range, 46-76 years; mean age, 64.8 years) with intrathoracic masses suggesting possible malignancy on the basis of chest radiography or CT underwent preoperative Tc-99m MIBI SPECT examinations. Diagnosis was confirmed on pathologic examinations of samples obtained either at thoracotomy, esophagectomy, or by biopsy. Twenty-five patients had primary lung cancer, including squamous cell carcinoma, large cell carcinoma, adenocarcinoma, and small cell carcinoma. Two patients had lymphomas with spread to the mediastinum, and three patients had extrathoracic primary cancers (one squamous cell carcinoma of esophagus, one squamous cell carcinoma originating from a head and neck tumor, and one metastatic mediastinal leiomyosarcoma). One patient with a tuberculoma had negative results of the Tc-99m MIBI examination. Tc-99m MIBI had a 86.7% sensitivity rate, a 0% false-positive rate, and a 100% positive predictive value to detect malignant intrathoracic masses. There was a 13% false-negative rate, however, suggesting that MIBI-SPECT may underdiagnose malignant lesions. SPECT findings of these 31 patients can be classified as 1) mass with increased uptake, n = 23; 2) ring-like appearance of increased uptake, n = 3; 3) mass with absent uptake, n = 4; and 4) photon-deficient mass, n = 1. Absent uptake in patients with mass lesions could be explained by necrosis of the lesion (caseation necrosis or massive tumor necrosis with or without bleeding). Most malignant intrathoracic masses are Tc-99m MIBI avid and may be detected with a high degree of sensitivity and with an excellent positive predictive value. A positive MIBI scan may help in the clinical diagnosis of malignancy. The use of Tc-99m MIBI could serve not only as a tumor imaging agent, but also may be used to determine the extent of spread and potentially the chemotherapeutic responsiveness of a tumor.     

An emergency aircraft evacuation simulation considering passenger emotions

The evacuation behavior of passengers was formulated as an autonomous agent and multi-agent model (AAMAS) evolving over a two-dimensional grid cell that represents aircraft cabins and passengers. In this model, the autonomous agents are initially placed in seat squares and move toward an emergency exit after an aircraft accident occurs. The autonomous agent mimics the behavior of passengers in the cabin, who must not only view their surroundings to collect the useful information but also select a route to an emergency exit. As the situation evolves, the agents feel the mental stress or strong fear or anxiety; thereby reacting unfavorably in the situation that they panic at. This abnormal evacuation behavior of panic agents generates time delays in the evacuation flow towards the exits. Therefore, such panic and its effect on evacuation behavior should be considered as an important factor in evacuation simulations. In this paper, it is supposed that the level of panic depends on three factors: remaining time, frequency of waiting and the difficulty of finding an exit. The dependencies of these factors on the time needed to complete an evacuation and the number of the panic agents in the aircraft were determined by the simulation. Considering the simulation results and situations of the actual aircraft accident “Garuda Indonesia Airways Accident”, it was possible to develop aircraft evacuation scenarios that considered passenger emotions.     

Characterization of the PP2A alpha gene mutation in okadaic acid-resistant variants of CHO-K1 cells

Okadaic acid (OA)-resistant variants of Chinese hamster ovary cells, clones CHO/OAR6-6 and CHO/OAR2-3, were isolated from a CHO-K1 culture. These variant cells were 17- to 26-fold more resistant to OA than the parental cells. The phosphorylase phosphatase activity of the variant cell extracts was 2- to 4-fold more resistant to OA than that of the parental cells in the presence of inhibitor 2, a specific inhibitor of type 1 protein serine/threonine phosphatase (PP1). Nucleotide sequencing of PP2A alpha (an isotype of PP2A catalytic subunit) cDNA demonstrated that both variants have a T-->G transversion at the first base of codon 269 (805 nt), which results in substitution of glycine for cysteine. We expressed in COS-1 cells a mutant PP2A alpha tagged with the influenza hemagglutinin epitope. The recombinant mutant PP2A alpha protein immunoprecipitated with an anti-influenza hemagglutinin antibody was more resistant than the wild type to OA, their IC50 values being 0.65 nM and 0.15 nM, and their IC80 values being 4.0 nM and 0.45 nM, respectively. The cysteine at residue 269 present only in highly OA-sensitive protein serine/threonine phosphatase catalytic subunit isozymes, PP2A alpha, PP2A beta, and PPX, is suggested to be involved in the binding of OA. CHO/OAR6-6 and CHO/OAR2-3 cells also overexpressed the P-glycoprotein, and the efflux of OA was more rapid. It is suggested that the PP2A alpha mutation in cooperation with a high level of P-glycoprotein makes the CHO-K1 variants highly resistant to OA.     

Development of the radiation-hardened Magnetically Suspended Compound Molecular Pump

The Magnetically Suspended Compound Molecule Pump is used for the vacuum pumping system in the 3 GeV Rapid Cycle Synchrotron (3 GeV-RCS) at Japan Proton Accelerator Research Complex (J-PARC). Due to the radiation environment it is used under, the pump must be resistant to at least 10 MGy of radiation. The standard Magnetically Suspended Compound Molecular Pump is only capable of withstanding up to 3.5 MGy under the radiation environment. For this reason, the radiation-hardened Magnetically Suspended Compound Molecular Pump was developed based on the gamma-ray irradiation examination results for the standard Magnetically Suspended Compound Molecular Pump, and an irradiation test was performed. The radiation-hardened Magnetically Suspended Compound Molecular Pump got a sensor tuning error when the accumulative radiation dose reached to 73.8 MGy. As a result of a disassembly check, cause of the failure was determined to be a decreased movement of the shaft due to the deformation of epoxy resin for the mandrel. However, all other parts such as the position sensor, the electromagnet and the motor, were no problem.     

Study of the pharmacological effect of the bile salt, sodium scymnol sulfate, from Rhizoprionodon acutus. II. Prophylactic effect of scymnol on lesion development in a rat peripheral arterial occlusion model

OBJECTIVE: To determine the rate of late complications following first implantation or elective unit replacement of a permanent pacemaker system. DESIGN: Analysis of pacemaker data and complications prospectively acquired on a computerised database. Complications were studied over an 11 year period from January 1984 to December 1994. SETTING: Tertiary referral cardiothoracic centre. PATIENTS: Records of 2621 patients were analysed retrospectively. MAIN OUTCOME MEASURES: Complications requiring repeat procedures occurring more than six weeks after pacemaker implantation or elective unit replacement. RESULTS: The overall rate of late complications was significantly lower after first implantation of a permanent pacemaker (34 cases, complication rate 1.4%, 95% confidence interval 0.9% to 1.9%) than after elective unit replacement (16 cases, complication rate 6.5% (3.3% to 9.7%). There were 20 cases of erosion, 18 infections, five electrode problems, and seven miscellaneous problems. Complications were more common with inexperienced operators (18.9% (6.0% to 31.8%)) than with experienced operators (0.9% (0.3% to 1.5%). CONCLUSIONS: The incidence of late complications following pacemaker implantation is low and compares favourably with early complication rates. The majority are caused by erosion and infection. Patients who have undergone elective unit replacement are at particular risk.     

A comparative study of failure criteria in probabilistic fields and stochastic failure envelopes of composite materials

One of the major objectives of this paper is to offer a practical tool for materials design of unidirectional composite laminates under in-plane multiaxial load. Design-oriented failure criteria of composite materials are applied to construct the evaluation model of probabilistic safety based on the extended structural reliability theory. Typical failure criteria such as maximum stress, maximum strain and quadratic polynomial failure criteria are compared from the viewpoint of reliability-oriented materials design of composite materials. The new design diagram which shows the feasible region on in-plane strain space and corresponds to safety index or failure probability is also proposed. These stochastic failure envelope diagrams which are drawn in in-plane strain space enable one to evaluate the stochastic behavior of a composite laminate with any lamination angle under multi-axial stress or strain condition. Numerical analysis for a graphite/epoxy laminate of T300/5208 is shown for the comparative verification of failure criteria under the various combinations of multi-axial load conditions and lamination angles. The stochastic failure envelopes of T300/5208 were also described in in-plane strain space.     

Local Chemical Bonding around Rare-Earth Ions in α- and ß-Si3N4

First-principles molecular-orbital calculations of α- and ß-Si₃N₄ with a trivalent lanthanide (Ln³⁺) ion at the interstitial site are conducted using model clusters that are composed of 41-43 atoms, neglecting lattice relaxation effects. When an interstitial Ln³⁺ ion is present, strong antibonding between the Ln³⁺ ion and Si₃N₄ is found. The magnitude of the antibonding is almost the same between the alpha- and ß-Si₃N₄ matrices. On the other hand, the Si-N bond around the Ln³⁺ ion is notably reinforced in alpha-Si₃N₄ but not so much in ß-Si₃N₄. The different electronic response to the presence of the Ln³⁺ ion for the Si-N bond is concluded to be the origin of the different solubilities of interstitial Ln³⁺ ions between alpha- and ß-SiAlONs that are reported experimentally. The contribution of the electric field that is induced by the presence of a trivalent charge at the interstitial site is examined in detail; we have found that the Si-N bond strength is not simply determined by the electric field but rather in a more complex manner.