Mie University

Abstract A description of the ab initio quantum chemistry package GAMESS is presented. Chemical systems containing atoms through radon can be treated with wave functions ranging from the simplest closed‐shell case up to a general MCSCF case, permitting calculations at the necessary level of sophistication. Emphasis is given to novel features of the program. The parallelization strategy used in the RHF, ROHF, UHF, and GVB sections of the program is described, and detailed speecup results are given. Parallel calculations can be run on ordinary workstations as well as dedicated parallel machines. © John Wiley & Sons, Inc.

The small guanosine triphosphatase Rho is implicated in myosin light chain (MLC) phosphorylation, which results in contraction of smooth muscle and interaction of actin and myosin in nonmuscle cells. The guanosine triphosphate (GTP)-bound, active form of RhoA (GTP.RhoA) specifically interacted with the myosin-binding subunit (MBS) of myosin phosphatase, which regulates the extent of phosphorylation of MLC. Rho-associated kinase (Rho-kinase), which is activated by GTP.RhoA, phosphorylated MBS and consequently inactivated myosin phosphatase. Overexpression of RhoA or activated RhoA in NIH 3T3 cells increased phosphorylation of MBS and MLC. Thus, Rho appears to inhibit myosin phosphatase through the action of Rho-kinase.

autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.

The small GTPase Rho is implicated in physiological functions associated with actin-myosin filaments such as cytokinesis, cell motility, and smooth muscle contraction. We have recently identified and molecularly cloned Rho-associated serine/threonine kinase (Rho-kinase), which is activated by GTP Rho (Matsui, T., Amano, M., Yamamoto, T., Chihara, K., Nakafuku, M., Ito, M., Nakano, T., Okawa, K., Iwamatsu, A., and Kaibuchi, K. (1996) EMBO J. 15, 2208-2216). Here we found that Rho-kinase stoichiometrically phosphorylated myosin light chain (MLC). Peptide mapping and phosphoamino acid analyses revealed that the primary phosphorylation site of MLC by Rho-kinase was Ser-19, which is the site phosphorylated by MLC kinase. Rho-kinase phosphorylated recombinant MLC, whereas it failed to phosphorylate recombinant MLC, which contained Ala substituted for both Thr-18 and Ser-19. We also found that the phosphorylation of MLC by Rho-kinase resulted in the facilitation of the actin activation of myosin ATPase. Thus, it is likely that once Rho is activated, then it can interact with Rho-kinase and activate it. The activated Rho-kinase subsequently phosphorylates MLC. This may partly account for the mechanism by which Rho regulates cytokinesis, cell motility, or smooth muscle contraction.

There is accumulating evidence that T-cell-mediated dominant control of self-reactive T-cells contributes to the maintenance of immunologic self-tolerance and its alteration can cause autoimmune disease. Efforts to delineate such a regulatory T-cell population have revealed that CD25+ cells in the CD4+ population in normal naive animals bear the ability to prevent autoimmune disease in vivo and, upon antigenic stimulation, suppress the activation/proliferation of other T cells in vitro. The CD25+ CD4+ regulatory T cells, which are naturally anergic and suppressive, appear to be produced by the normal thymus as a functionally distinct subpopulation of T cells. They play critical roles not only in preventing autoimmunity but also in controlling tumor immunity and transplantation tolerance.

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MALE accessory sex glands such as the prostate, seminal vesicle, and bulbourethral gland have served in various capacities as models for investigating the action of androgens in regulating epithelial growth, RNA and protein synthesis, and secretory activity. The most extensively studied gland of this group is the prostate. This gland is found exclusively in mammals and produces many components of semen such as fructose, zinc ions, and various proteins important for the formation of the copulatory plug in rodents. The impetus for investigating regulation of prostatic growth and function stems in part from the many pathological complications which affect this gland. The prostate is the site of various types of inflammatory and infectious conditions (1) as well as benign and malignant proliferative changes in aging males. Despite extensive research, little of the pathogenesis or natural history of these diseases has been elucidated (2). Benign prostatic hypertrophy (BPH), a disease in which the prostate resumes growth late in life, is the most common nonmalignant proliferative abnormality found in any internal organ (2). The incidence of BPH rises from 23% in men at 40 yr of age to 88% by the ninth decade (3). Adenocarcinoma of the prostate is the third leading cause of cancer deaths among men. Approximately 69 cases/100,000 men are diagnosed each year in the United States. It remains an intriguing paradox that malignant prostatic tumors are among the most prevalent neoplasms in men, while the seminal vesicles and bubulbourethral gland remain nearly immune to neoplastic change (<1 case of carcinoma of the seminal vesicle per year) (4).

A 5 year research on concrete-filled steel tubular (CFT) column system was carried out as a part of the fifth phase of the U.S.–Japan Cooperative Earthquake Research Program, and the tests of centrally loaded short columns were finished. The objectives of these tests were to clarify the synergistic interaction between steel tube and filled concrete, and to derive methods to characterize the load–deformation relationship of CFT columns. A total of 114 specimens was fabricated and tested in the experimental phase of investigations on centrally loaded hollow and CFT short columns. Parameters for the tests are as follows: (1) tube shape, (2) tube tensile strength, (3) tube diameter-to-thickness ratio, and (4) concrete strength. In determining the range of parameters, the emphasis was placed on obtaining a wide range of test data for establishing a generally applicable design method of CFT column systems. Design formulas to estimate the ultimate axial compressive load capacities are proposed for CFT columns with both circular and square sections based on tests results described in this paper.

The mammalian nervous system constantly evaluates internal and environmental temperatures to maintain homeostasis and to avoid thermal extremes. Several members of the transient receptor potential (TRP) family of ion channels have been implicated as transducers of thermal stimuli, including TRPV1 and TRPV2, which are activated by heat, and TRPM8, which is activated by cold. Here we demonstrate that another member of the TRP family, TRPV4, previously described as a hypo-osmolarity-activated ion channel, also can be activated by heat. In response to warm temperatures, TRPV4 mediates large inward currents in Xenopus oocytes and both inward currents and calcium influx into human embryonic kidney 293 cells. In both cases these responses are observed at temperatures lower than those required to activate TRPV1 and can be inhibited reversibly by ruthenium red. Heat-evoked TRPV4-mediated responses are greater in hypo-osmotic solutions and reduced in hyperosmotic solutions. Consistent with these functional properties, we observed TRPV4 immunoreactivity in anterior hypothalamic structures involved in temperature sensation and the integration of thermal and osmotic information. Together, these data implicate TRPV4 as a possible transducer of warm stimuli within the hypothalamus.

We made a series of improved Gateway binary vectors (pGWBs) for plant transformation. Fifteen different reporters and tags, sGFP, GUS, LUC, EYFP, ECFP, G3GFP, mRFP, 6xHis, FLAG, 3xHA, 4xMyc, 10xMyc, GST, T7, and TAP, were employed. Some vectors carry the 2x35S-Omega promoter for higher-level expression. The kanamycin- and hygromycin-resistant markers are independently available for each of the 43 types of vectors, thus an additional transformation of once-transformed plants can be carried out easily. Their small size and high-copy number in Escherichia coli make possible easier handling at plasmid preparation and sequencing. Improved pGWBs should be a powerful tool for transgenic research in plants.

Recent studies have revealed that Foxp3(+)CD25(+)CD4(+) regulatory T cells (Tregs), which are physiologically engaged in the maintenance of immunological self-tolerance, play critical roles for the control of antitumor immune responses. For example, a large number of Foxp3(+)Tregs infiltrate into tumors, and systemic removal of Foxp3(+)Tregs enhances natural as well as vaccine-induced antitumor T-cell responses. Tregs are recruited to tumor tissues via chemokines, such as CCL22 binding to CCR4 expressed by Tregs. They appear to expand and become activated in tumor tissues and in the draining lymph nodes by recognizing tumor-associated antigens as well as normal self-antigen expressed by tumor cells. These results indicate that cancer vaccines targeting tumor-associated self-antigens may potentially expand/activate Tregs and hamper effective antitumor immune responses, and that tumor immunity can therefore be enhanced by depleting Tregs, attenuating Treg suppressive function, or rendering effector T cells refractory to Treg-mediated suppression. Recent attempts have indeed demonstrated that combinations of monoclonal antibodies capable of modulating Treg functions synergistically enhance antitumor activity and are more effective than a single monoclonal antibody therapy. Combination therapy targeting a variety of molecules expressed in antigen-presenting cells, effector T cells and Tregs is envisaged to be a promising anticancer immunotherapy.

Abstract Crystallinity was measured by X‐ray diffraction method and water‐saturated state was determined by means of the moisture contents calculated from the crystallinity for moistened cellulose and potato starch. In the X‐ray diffractograms the upper areas which were separated by the straight line joined the points of intensity at 37° and 4° (8°) of diffraction angle was the relative reflection area in the crystalline and amorphous portions, and the lower area was the background of the non‐relative reflection area. The upper area separated by the smooth curve joined the minimum intensity at 4° to 37° of diffraction angle corresponded to the crystalline portion and the lower area to the amorphous one. The ratio of the crystalline portion to sum of the crystalline and amorphous portions was considered to be crystallinity. Crystallinity of the air‐dried and the moisture‐saturated (28%) samples of cellulose were 0.68 and 0.71, resp. The crystallinity of the air‐dried and water‐saturated (49%) samples of potato starch were 0.24 and 0.32, resp.

Pulsed laser vaporization of a heated, Fe/Ni or Co/Ni catalyzed, carbon target in argon gas has been used to synthesize single-wall carbon nanotubes (SWNTs). Electron microscopy, x-ray diffraction, and Raman spectroscopy were all used to study the effect of the catalyst on the tube yield, and the evolution of the tube diameter distribution with increasing growth environment temperature $T$. By controlling the temperature in the range $780&lt;T&lt;1050\ifmmode^\circ\else\textdegree\fi{}\mathrm{C}$, we have been able to tune the diameter of the tubules from $\ensuremath{\sim}0.81$ to $\ensuremath{\sim}1.51\mathrm{nm}$. The threshold temperature for significant SWNT production was found to be $\ensuremath{\sim}850\ifmmode^\circ\else\textdegree\fi{}\mathrm{C}$.

During the last decade, many sensorless control methods have been proposed for surface permanent-magnet synchronous motors (SPMSMs) based on the estimation of electromotive force (EMF) in which the motor's position information is contained. However, these methods cannot be applied to interior PMSMs (IPMSMs) directly, because the position information is contained in not only the EMF, but also the inductance of stators. In this paper, a new mathematical model for IPMSMs is proposed and an extended EMF is defined, which includes both position information from the EMF and the stator inductance. By using the newly proposed model, sensorless controls proposed for SPMSMs can easily be applied to IPMSMs. As an example, a disturbance observer is studied and the experimental results show that the proposed method on the proposed model is very effective.

There are T cells within normal, noninflamed skin that most likely conduct immunosurveillance and are implicated in the development of psoriasis. We isolated T cells from normal human skin using both established and novel methods. Skin resident T cells expressed high levels of CLA, CCR4, and CCR6, and a subset expressed CCR8 and CXCR6. Skin T cells had a remarkably diverse TCR repertoire and were mostly Th1 memory effector cells with smaller subsets of central memory, Th2, and functional T regulatory cells. We isolated a surprising number of nonexpanded T cells from normal skin. To validate this finding, we counted T cells in sections of normal skin and determined that there are approximately 1 x 10(6) T cells/cm(2) normal skin and an estimated 2 x 10(10) T cells in the entire skin surface, nearly twice the number of T cells in the circulation. Moreover, we estimate that 98% of CLA(+) effector memory T cells are resident in normal skin under resting conditions. These findings demonstrate that there is a large pool of memory T cells in normal skin that can initiate and perpetuate immune reactions in the absence of T cell recruitment from the blood.

This statement was developed to promote international consensus on the definition of borderline resectable pancreatic ductal adenocarcinoma (BR-PDAC) which was adopted by the National Comprehensive Cancer Network (NCCN) in 2006, but which has changed yearly and become more complicated. Based on a symposium held during the 20th meeting of the International Association of Pancreatology (IAP) in Sendai, Japan, in 2016, the presenters sought consensus on issues related to BR-PDAC. We defined patients with BR-PDAC according to the three distinct dimensions: anatomical (A), biological (B), and conditional (C). Anatomic factors include tumor contact with the superior mesenteric artery and/or celiac artery of less than 180° without showing stenosis or deformity, tumor contact with the common hepatic artery without showing tumor contact with the proper hepatic artery and/or celiac artery, and tumor contact with the superior mesenteric vein and/or portal vein including bilateral narrowing or occlusion without extending beyond the inferior border of the duodenum. Biological factors include potentially resectable disease based on anatomic criteria but with clinical findings suspicious for (but unproven) distant metastases or regional lymph nodes metastases diagnosed by biopsy or positron emission tomography-computed tomography. This also includes a serum carbohydrate antigen (CA) 19-9 level more than 500 units/ml. Conditional factors include the patients with potentially resectable disease based on anatomic and biologic criteria and with Eastern Cooperative Oncology Group (ECOG) performance status of 2 or more. The definition of BR-PDAC requires one or more positive dimensions (e.g. A, B, C, AB, AC, BC or ABC). The present definition acknowledges that resectability is not just about the anatomic relationship between the tumor and vessels, but that biological and conditional dimensions are also important. The aim in presenting this consensus definition is also to highlight issues which remain controversial and require further research.

Exosomes are a valuable biomaterial for the development of novel nanocarriers as functionally advanced drug delivery systems. To control and modify the performance of exosomal nanocarriers, we developed hybrid exosomes by fusing their membranes with liposomes using the freeze-thaw method. Exosomes embedded with a specific membrane protein isolated from genetically modified cells were fused with various liposomes, confirming that membrane engineering methods can be combined with genetic modification techniques. Cellular uptake studies performed using the hybrid exosomes revealed that the interactions between the developed exosomes and cells could be modified by changing the lipid composition or the properties of the exogenous lipids. These results suggest that the membrane-engineering approach reported here offers a new strategy for developing rationally designed exosomes as hybrid nanocarriers for use in advanced drug delivery systems.

BACKGROUND: Olfactory dysfunction is an increasingly recognised condition, associated with reduced quality of life and major health outcomes such as neurodegeneration and death. However, translational research in this field is limited by heterogeneity in methodological approach, including definitions of impairment, improvement and appropriate assessment techniques. Accordingly, effective treatments for smell loss are limited. In an effort to encourage high quality and comparable work in this field, among others, we propose the following ideas and recommendations. Whilst the full set of recommendations are outlined in the main document, points include the following: - Patients with suspected olfactory loss should undergo a full examination of the head and neck, including rigid nasal endoscopy with small diameter endoscopes. - Subjective olfactory assessment should not be undertaken in isolation, given its poor reliability. - Psychophysical assessment tools used in clinical and research settings should include reliable and validated tests of odour threshold, and/or one of odour identification or discrimination. - Comprehensive chemosensory assessment should include gustatory screening. - Smell training can be helpful in patients with olfactory loss of several aetiologies. CONCLUSIONS: We hope the current manuscript will encourage clinicians and researchers to adopt a common language, and in so doing, increase the methodological quality, consistency and generalisability of work in this field.

The controlled-valence properties of ${\mathrm{La}}_{1\mathrm{\ensuremath{-}}\mathit{x}}$${\mathrm{Sr}}_{\mathit{x}}$${\mathrm{FeO}}_{3}$ and ${\mathrm{La}}_{1\mathrm{\ensuremath{-}}\mathit{x}}$${\mathrm{Sr}}_{\mathit{x}}$${\mathrm{MnO}}_{3}$ are studied by means of soft-x-ray absorption spectroscopy. A comparison between the transition-metal 2p spectra and atomic-multiplet calculations is used to determine the 3d count. The O 1s spectrum is used to characterize changes in unoccupied states that contain oxygen p character. The results indicate that the holes induced by substitution for both series are located in states of mixed metal 3d--oxygen 2p character. The ground state of ${\mathrm{LaFeO}}_{3}$ is mainly 3${\mathit{d}}^{5}$ and becomes 3${\mathit{d}}^{5}$L (where L denotes a ligand hole) in the ${\mathrm{La}}_{1\mathrm{\ensuremath{-}}\mathit{x}}$${\mathrm{Sr}}_{\mathit{x}}$${\mathrm{FeO}}_{3}$ series for low Sr concentration. The main component of the ground state of ${\mathrm{LaMnO}}_{3}$ is 3${\mathit{d}}^{4}$ and becomes a mixture of 3${\mathit{d}}^{3}$ and 3${\mathit{d}}^{4}$L in the ${\mathrm{La}}_{1\mathrm{\ensuremath{-}}\mathit{x}}$${\mathrm{Sr}}_{\mathit{x}}$${\mathrm{MnO}}_{3}$ series. The trends in controlled- valence properties of similar oxides across the transition-metal series can be rationalized within the framework of the Zaanen-Sawatzky-Allen model.

BACKGROUND: Chronic rhinosinusitis (CRS) can be classified into CRS with nasal polyps (CRSwNP) and CRS without nasal polyps (CRSsNP). CRSwNP displays more intense eosinophilic infiltration and the presence of Th2 cytokines. Mucosal eosinophilia is associated with more severe symptoms and often requires multiple surgeries because of recurrence; however, even in eosinophilic CRS (ECRS), clinical course is variable. In this study, we wanted to set objective clinical criteria for the diagnosis of refractory CRS. METHODS: This was a retrospective study conducted by 15 institutions participating in the Japanese Epidemiological Survey of Refractory Eosinophilic Chronic Rhinosinusitis (JESREC). We evaluated patients with CRS treated with endoscopic sinus surgery (ESS), and risk of recurrence was estimated using Cox proportional hazard models. Multiple logistic regression models and receiver operating characteristics curves were constructed to create the diagnostic criterion for ECRS. RESULTS: We analyzed 1716 patients treated with ESS. To diagnose ECRS, the JESREC scoring system assessed unilateral or bilateral disease, the presence of nasal polyps, blood eosinophilia, and dominant shadow of ethmoid sinuses in computed tomography (CT) scans. The cutoff value of the score was 11 points (sensitivity: 83%, specificity: 66%). Blood eosinophilia (>5%), ethmoid sinus disease detected by CT scan, bronchial asthma, aspirin, and nonsteroidal anti-inflammatory drugs intolerance were associated significantly with recurrence. CONCLUSION: We subdivided CRSwNP in non-ECRS, mild, moderate, and severe ECRS according to our algorithm. This classification was significantly correlated with prognosis. It is notable that this algorithm may give useful information to clinicians in the refractoriness of CRS before ESS or biopsy.