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Abstract. In this paper, we give a new proof of Iv´ady double inequality: for x > 0, we have √1 − exp − x²/ (1 + x²) 1/2 < tanh x < ³√ 1 − exp − x³/ (1 + x³) 1/2. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study is to estimate the extent to which the implementation of deep learning reconstruction (DLR) may reduce the risk of radiation-induced cancer from CT examinations, utilizing real-world clinical data.We retrospectively analyzed scan data of adult patients who underwent body CT during two periods relative to DLR implementation at our facility: a 12-month pre-DLR phase (n = 5553) using hybrid iterative reconstruction and a 12-month post-DLR phase (n = 5494) with routine CT reconstruction transitioning to DLR. To ensure comparability between two groups, we employed propensity score matching 1:1 based on age, sex, and body mass index. Dose data were collected to estimate organ-specific equivalent doses and total effective doses. We assessed the average dose reduction post-DLR implementation and estimated the Lifetime Attributable Risk (LAR) for cancer per CT exam pre- and post-DLR implementation. The number of radiation-induced cancers before and after the implementation of DLR was also estimated.After propensity score matching, 5247 cases from each group were included in the final analysis. Post-DLR, the total effective body CT dose significantly decreased to 15.5 ± 10.3 mSv from 28.1 ± 14.0 mSv pre-DLR (p < 0.001), a 45% reduction. This dose reduction significantly lowered the radiation-induced cancer risk, especially among younger women, with the estimated annual cancer incidence from 0.247% pre-DLR to 0.130% post-DLR.The implementation of DLR has the possibility to reduce radiation dose by 45% and the risk of radiation-induced cancer from 0.247 to 0.130% as compared with the iterative reconstruction.QuestionCan implementing deep learning reconstruction (DLR) in routine CT scans significantly reduce radiation dose and the risk of radiation-induced cancer compared to hybrid iterative reconstruction?FindingsDLR reduced the total effective body CT dose by 45% (from 28.1 ± 14.0 mSv to 15.5 ± 10.3 mSv) and decreased estimated cancer incidence from 0.247 to 0.130%.Clinical relevanceAdopting DLR in clinical practice substantially lowers radiation exposure and cancer risk from CT exams, enhancing patient safety, especially for younger women, and underscores the importance of advanced imaging techniques.Methods: The purpose of this study is to estimate the extent to which the implementation of deep learning reconstruction (DLR) may reduce the risk of radiation-induced cancer from CT examinations, utilizing real-world clinical data.We retrospectively analyzed scan data of adult patients who underwent body CT during two periods relative to DLR implementation at our facility: a 12-month pre-DLR phase (n = 5553) using hybrid iterative reconstruction and a 12-month post-DLR phase (n = 5494) with routine CT reconstruction transitioning to DLR. To ensure comparability between two groups, we employed propensity score matching 1:1 based on age, sex, and body mass index. Dose data were collected to estimate organ-specific equivalent doses and total effective doses. We assessed the average dose reduction post-DLR implementation and estimated the Lifetime Attributable Risk (LAR) for cancer per CT exam pre- and post-DLR implementation. The number of radiation-induced cancers before and after the implementation of DLR was also estimated.After propensity score matching, 5247 cases from each group were included in the final analysis. Post-DLR, the total effective body CT dose significantly decreased to 15.5 ± 10.3 mSv from 28.1 ± 14.0 mSv pre-DLR (p < 0.001), a 45% reduction. This dose reduction significantly lowered the radiation-induced cancer risk, especially among younger women, with the estimated annual cancer incidence from 0.247% pre-DLR to 0.130% post-DLR.The implementation of DLR has the possibility to reduce radiation dose by 45% and the risk of radiation-induced cancer from 0.247 to 0.130% as compared with the iterative reconstruction.QuestionCan implementing deep learning reconstruction (DLR) in routine CT scans significantly reduce radiation dose and the risk of radiation-induced cancer compared to hybrid iterative reconstruction?FindingsDLR reduced the total effective body CT dose by 45% (from 28.1 ± 14.0 mSv to 15.5 ± 10.3 mSv) and decreased estimated cancer incidence from 0.247 to 0.130%.Clinical relevanceAdopting DLR in clinical practice substantially lowers radiation exposure and cancer risk from CT exams, enhancing patient safety, especially for younger women, and underscores the importance of advanced imaging techniques.Results: The purpose of this study is to estimate the extent to which the implementation of deep learning reconstruction (DLR) may reduce the risk of radiation-induced cancer from CT examinations, utilizing real-world clinical data.We retrospectively analyzed scan data of adult patients who underwent body CT during two periods relative to DLR implementation at our facility: a 12-month pre-DLR phase (n = 5553) using hybrid iterative reconstruction and a 12-month post-DLR phase (n = 5494) with routine CT reconstruction transitioning to DLR. To ensure comparability between two groups, we employed propensity score matching 1:1 based on age, sex, and body mass index. Dose data were collected to estimate organ-specific equivalent doses and total effective doses. We assessed the average dose reduction post-DLR implementation and estimated the Lifetime Attributable Risk (LAR) for cancer per CT exam pre- and post-DLR implementation. The number of radiation-induced cancers before and after the implementation of DLR was also estimated.After propensity score matching, 5247 cases from each group were included in the final analysis. Post-DLR, the total effective body CT dose significantly decreased to 15.5 ± 10.3 mSv from 28.1 ± 14.0 mSv pre-DLR (p < 0.001), a 45% reduction. This dose reduction significantly lowered the radiation-induced cancer risk, especially among younger women, with the estimated annual cancer incidence from 0.247% pre-DLR to 0.130% post-DLR.The implementation of DLR has the possibility to reduce radiation dose by 45% and the risk of radiation-induced cancer from 0.247 to 0.130% as compared with the iterative reconstruction.QuestionCan implementing deep learning reconstruction (DLR) in routine CT scans significantly reduce radiation dose and the risk of radiation-induced cancer compared to hybrid iterative reconstruction?FindingsDLR reduced the total effective body CT dose by 45% (from 28.1 ± 14.0 mSv to 15.5 ± 10.3 mSv) and decreased estimated cancer incidence from 0.247 to 0.130%.Clinical relevanceAdopting DLR in clinical practice substantially lowers radiation exposure and cancer risk from CT exams, enhancing patient safety, especially for younger women, and underscores the importance of advanced imaging techniques.Conclusion: The purpose of this study is to estimate the extent to which the implementation of deep learning reconstruction (DLR) may reduce the risk of radiation-induced cancer from CT examinations, utilizing real-world clinical data.We retrospectively analyzed scan data of adult patients who underwent body CT during two periods relative to DLR implementation at our facility: a 12-month pre-DLR phase (n = 5553) using hybrid iterative reconstruction and a 12-month post-DLR phase (n = 5494) with routine CT reconstruction transitioning to DLR. To ensure comparability between two groups, we employed propensity score matching 1:1 based on age, sex, and body mass index. Dose data were collected to estimate organ-specific equivalent doses and total effective doses. We assessed the average dose reduction post-DLR implementation and estimated the Lifetime Attributable Risk (LAR) for cancer per CT exam pre- and post-DLR implementation. The number of radiation-induced cancers before and after the implementation of DLR was also estimated.After propensity score matching, 5247 cases from each group were included in the final analysis. Post-DLR, the total effective body CT dose significantly decreased to 15.5 ± 10.3 mSv from 28.1 ± 14.0 mSv pre-DLR (p < 0.001), a 45% reduction. This dose reduction significantly lowered the radiation-induced cancer risk, especially among younger women, with the estimated annual cancer incidence from 0.247% pre-DLR to 0.130% post-DLR.The implementation of DLR has the possibility to reduce radiation dose by 45% and the risk of radiation-induced cancer from 0.247 to 0.130% as compared with the iterative reconstruction.QuestionCan implementing deep learning reconstruction (DLR) in routine CT scans significantly reduce radiation dose and the risk of radiation-induced cancer compared to hybrid iterative reconstruction?FindingsDLR reduced the total effective body CT dose by 45% (from 28.1 ± 14.0 mSv to 15.5 ± 10.3 mSv) and decreased estimated cancer incidence from 0.247 to 0.130%.Clinical relevanceAdopting DLR in clinical practice substantially lowers radiation exposure and cancer risk from CT exams, enhancing patient safety, especially for younger women, and underscores the importance of advanced imaging techniques.Key Points: The purpose of this study is to estimate the extent to which the implementation of deep learning reconstruction (DLR) may reduce the risk of radiation-induced cancer from CT examinations, utilizing real-world clinical data.We retrospectively analyzed scan data of adult patients who underwent body CT during two periods relative to DLR implementation at our facility: a 12-month pre-DLR phase (n = 5553) using hybrid iterative reconstruction and a 12-month post-DLR phase (n = 5494) with routine CT reconstruction transitioning to DLR. To ensure comparability between two groups, we employed propensity score matching 1:1 based on age, sex, and body mass index. Dose data were collected to estimate organ-specific equivalent doses and total effective doses. We assessed the average dose reduction post-DLR implementation and estimated the Lifetime Attributable Risk (LAR) for cancer per CT exam pre- and post-DLR implementation. The number of radiation-induced cancers before and after the implementation of DLR was also estimated.After propensity score matching, 5247 cases from each group were included in the final analysis. Post-DLR, the total effective body CT dose significantly decreased to 15.5 ± 10.3 mSv from 28.1 ± 14.0 mSv pre-DLR (p < 0.001), a 45% reduction. This dose reduction significantly lowered the radiation-induced cancer risk, especially among younger women, with the estimated annual cancer incidence from 0.247% pre-DLR to 0.130% post-DLR.The implementation of DLR has the possibility to reduce radiation dose by 45% and the risk of radiation-induced cancer from 0.247 to 0.130% as compared with the iterative reconstruction.QuestionCan implementing deep learning reconstruction (DLR) in routine CT scans significantly reduce radiation dose and the risk of radiation-induced cancer compared to hybrid iterative reconstruction?FindingsDLR reduced the total effective body CT dose by 45% (from 28.1 ± 14.0 mSv to 15.5 ± 10.3 mSv) and decreased estimated cancer incidence from 0.247 to 0.130%.Clinical relevanceAdopting DLR in clinical practice substantially lowers radiation exposure and cancer risk from CT exams, enhancing patient safety, especially for younger women, and underscores the importance of advanced imaging techniques. [ABSTRACT FROM AUTHOR]

Various program verification problems for functional programs can be reduced to the validity checking problem for formulas of a fixpoint logic. Recently, Kobayashi et al. have shown that the unfold/fold transformation originally developed for logic programming can be extended and applied to prove the validity of fixpoint logic formulas. In the present paper, we refine their unfold/fold transformation, so that each predicate can be unfolded a different number of times in an asynchronous manner. Inspired by the work of Lee et al. on size change termination, we use a variant of size change graphs to find an appropriate number of unfoldings of each predicate. We have implemented an unfold/fold transformation tool based on the proposed method, and evaluated its effectiveness. [ABSTRACT FROM AUTHOR]

In 1970's, Nivat studied recursive program schemes (a.k.a order-1 higher-order recursion schemes in modern terminology), first-order tree grammars for generating possibly infinite trees. We consider the inclusion problem between the frontier language of a non-deterministic recursive program scheme (equivalently, an order-2 word language or indexed language) and the Dyck language, and prove that it is undecidable by a reduction from the undecidability of Hilbert's 10th problem. Essentially the same result has recently been proved by Uezato and Minamide, but our proof is arguably more direct, demonstrating the expressive power of higher-order grammars. [ABSTRACT FROM AUTHOR]

Examines surface diffusion and step-bunching mechanisms by high-vacuum scanning tunneling microscopy. Overview of gallium arsenide growth by metalorganic vapor-phase epitaxy; Value of the surface diffusion coefficient and surface diffusion length; Details of the two dimensional formed at different temperatures.

Focuses on a study which determined the catalytic fractional conversion required for the stable closed-cycle operation of the transversely excited atmospheric carbon dioxide laser under a wide range of operational conditions. Model description; Computational approach; Results and discussion.

Presents an analysis of the photoluminescence of AlAs-GaAs ultrashort superlattices grown by flow-rate modulation epitaxy. Overview of previous studies on the electronic structure of the AlAs-Gaas short period superlattices; Details of experimental techniques used; Reason behind the relation between lower-energy lines and phonon replicas.

Presents a study which described the growth of flow-rate modulation epitaxy (FME) conditions and electrical and optical properties of FME-grown gallium arsenide, AlGaAs layers and GaAs/AlGaAs single-quantum-well heterostructures. Difference between FME and atomic layer epitaxy; Growth conditions of FME; Properties of FME grown layers.

Focuses on a study which described the electronic transport characteristics of silicon atomic-layer-doped gallium arsenide grown by flowrate modulation epitaxy. Discussion of the parallel conduction model; Interpretation of the activation energy.

In the countries sailing with an economic tailwind, many skyscrapers are going up. These buildings require systems of high-speed, safety, and comfortable elevators for its speedy vertical transportation. If the drives of elevator fail, an emergency stop device is supposed to work immediately for saving passengers lives in the elevator cage, because the elevator has outrageous potential energy to the ground level and kinetic energy. Its dangerousness is nothing compared to that in railways as surface transport. In order to reduce impact force to passengers in emergency stoppage, the authors had already proposed a safe and dependable magnetorheological fluid (MRF) semi-active damper (i.e., MRF damper) put between an emergency stop device and an elevator cage. In this paper, in order to evaluate the effects of the MRF damper, we would like to make up a test installation, which is composed of an MRF damper, a spring, an elevator cage, linear servo mechanics with a ball screw for generating the brake force of emergency stop device, sensors, and a digital controller with Labview. In addition, we would like to verify the validity of our system by many experiments. [ABSTRACT FROM AUTHOR]

Novel 6 H -cyclohepta[ c ]furan derivatives possessing aryl groups on 1,3-position were synthesized, and their photophysical behavior were investigated. 1,3-Diphenyl-5,7-difomyl derivative showed solvatochromism. As the electron donating ability at 1,3-positions and the electron withdrawing ability at 5,7-positions increased, the absorption and emission wavelengths were bathochromically shifted. Theoretical calculations revealed that their photophysical behaviors are reproduced. [ABSTRACT FROM AUTHOR]

This report describes a novel, comprehensive approach to identifying a fragment peak of monoclonal antibody-A (mAb-A), detected by sodium dodecyl sulfate-capillary gel electrophoresis (SDS-cGE). The fragment migrated close to the internal standard (10 kDa marker) of SDS-cGE and increased about 0.5% under a 25 °C condition for 6 months. Generally, identification of fragments observed in SDS-cGE is challenging to carry out due to the difficulty of collecting analytical amounts of fractionations from the capillary. In this study, in-gel digestion peptide mapping and reversed phase liquid chromatography-mass spectrometry (RPLC–MS) were employed to elucidate the structure of the fragment. In addition, a Gelfree 8100 fractionation system was newly introduced to collect the fragment and the fraction was applied to the structural analysis of a mAb for the first time. These three analytical methods showed comparable results, proving that the fragment was a fraction of heavy chain HC1-104. The fragment contained complementarity determining regions (CDRs), which are significant to antigen binding, and thus would affect the efficacy of mAb-A. In addition, SDS-cGE without the 10 kDa marker was demonstrated to clarify the increased amount of the fragment, and the experiment revealed that the fragment increases 0.2% per year in storage at 5 °C. The combination of the three analytical methodologies successfully identified the impurity peak detected by SDS-cGE, providing information critical to assuring the quality and stability of the biotherapeutics. [ABSTRACT FROM AUTHOR]

Deadlock detection in concurrent programs that create networks with arbitrary numbers of nodes is extremely complex and solutions either give imprecise answers or do not scale. To enable the analysis of such programs, (1) we define an algorithm for detecting deadlocks of a basic model featuring recursion and fresh name generation: the lam programs , and (2) we design a type system for value-passing CCS that returns lam programs. We show the soundness of the type system, and develop a type inference algorithm for it. The resulting algorithm is able to check deadlock-freedom of programs that cannot be handled by previous analyses, such as those that build unbounded networks. [ABSTRACT FROM AUTHOR]

New 2,3-naphthalimide derivatives bearing phenyl substituents on the naphthalene skeleton were synthesized, and their UV/vis absorption and fluorescence properties were investigated. The fluorescence intensity of the short wavelength emission was strengthened as the increase in the number of the phenyl groups on the naphthalene skeleton. [ABSTRACT FROM AUTHOR]

Acquisition of cis-regulatory elements is a major driving force of evolution, and there are several examples of developmental enhancers derived from transposable elements (TEs). However, it remains unclear whether one enhancer element could have been produced via cooperation among multiple, yet distinct, TEs during evolution. Here we show that an evolutionarily conserved genomic region named AS3_9 comprises three TEs (AmnSINE1, X6b_DNA and MER117), inserted side-by-side, and functions as a distal enhancer for wnt5a expression during morphogenesis of the mammalian secondary palate. Functional analysis of each TE revealed step-by-step retroposition/transposition and co-option together with acquisition of a binding site for Msx1 for its full enhancer function during mammalian evolution. The present study provides a new perspective suggesting that a huge variety of TEs, in combination, could have accelerated the diversity of cis-regulatory elements involved in morphological evolution. [ABSTRACT FROM AUTHOR]

To elucidate the effect of fungal hyphae on the behaviour of Shiga toxin-producing Escherichia coli ( STEC) O157, the spread and change in stress resistance of the bacterium were evaluated after coculture with 11 species of food-related fungi including fermentation starters. Spread distances of STEC O157 varied depending on the co-cultured fungal species, and the motile bacterial strain spread for longer distances than the non-motile strain. The population of STEC O157 increased when co-cultured on colonies of nine fungal species but decreased on colonies of Emericella nidulans and Aspergillus ochraceus. Confocal scanning microscopy visualization of green fluorescent protein-tagged STEC O157 on fungal hyphae revealed that the bacterium colonized in the water film that existed on and between hyphae. To investigate the physiological changes in STEC O157 caused by co-culturing with fungi, the bacterium was harvested after 7 days of co-culturing and tested for acid resistance. After co-culture with eight fungal species, STEC O157 showed greater acid resistance compared to those cultured without fungi. Our results indicate that fungal hyphae can spread the contamination of STEC O157 and can also enhance the stress resistance of the bacteria. [ABSTRACT FROM AUTHOR]

Abstract: The prognosis for adult T cell leukemia/lymphoma (ATL) is very poor, and only allogeneic hematopoietic stem cell transplantation (allo-SCT) has been considered to be a curative treatment for ATL. In this study, we retrospectively analyzed data for patients who had received allo-SCT for ATL in Hokkaido, the northernmost island of Japan, to determine prognostic factors. Fifty-six patients with a median age of 57 years received allo-SCT. Twenty-eight (50.0%) patients had acute type and 22 (46.4%) had lymphoma type. Twenty-three (41.1%) patients received allo-SCT in complete remission (CR), whereas the others were in non-CR. Seventeen (30.4%) patients received myeloablative conditioning and the others received reduced-intensity conditioning. With a median follow-up period of 48 months (range, 17 to 134 months), 1-year overall survival (OS) and 5-year OS rates were 55.4% and 46.1%, respectively. The survival curve reached a plateau at 22 months after stem cell transplantation (SCT). Male sex, high level of serum soluble interleukin-2 receptor (sIL-2R) at SCT, and non-CR at SCT were determined to be significant risk factors for OS. A high level of sIL-2R at SCT was a risk factor for poor OS in patients with non-CR at SCT by univariate analysis (P = .02), and it remained significant after adjustment by sex (hazard ratio, 2.73 [95% confidence interval, 1.07 to 7.90]). A high level of sIL-2R at SCT was also determined to be a risk factor for disease progression (P = .02). This region-wide study showed encouraging results for survival after allo-SCT for ATL and demonstrated for the first time that a high level of sIL-2R at SCT predicts worse SCT outcome. [Copyright &y& Elsevier]

Abstract: Sphingosine 1-phosphate (S1P) is a lipid mediator that plays important roles in diverse cellular functions such as cell proliferation, differentiation and migration. S1P is synthesized inside the cells and subsequently released to the extracellular space, where it binds to specific receptors that are located on the plasma membranes of target cells. Accumulating recent evidence suggests that S1P transporters including SPNS2 mediate S1P release from the cells and are involved in the physiological functions of S1P. In this review, we discuss recent advances in our understanding of the mechanism and physiological functions of S1P transporters. This article is part of a Special Issue entitled New Frontiers in Sphingolipid Biology. [Copyright &y& Elsevier]

Lamb waves of the Earth's atmosphere in the millihertz band have been considered as transient phenomena excited only by large events. Here, we show the first evidence of background Lamb waves in the Earth's atmosphere from 0.2 to 10 mHz, based on the array analysis of microbarometer data from the USArray in 2012. The observations suggest that the probable excitation source is atmospheric turbulence in the troposphere. Theoretically, their energy in the troposphere tunnels into the thermosphere at a resonant frequency via thermospheric gravity wave, where the observed amplitudes indeed take a local minimum. The energy leak through the frequency window could partly contribute to thermospheric wave activity. [ABSTRACT FROM AUTHOR]

A series of [core+exo]-type Au8 clusters bearing two alkynyl ligands on the exo gold atoms ([Au8(dppp)4(C=CR)2]2+, 2-6) were synthesized by the reaction of [Au8(dppp)4]2+ (1) with alkynyl anions. Although the C=C moieties directly attached to the Au8 units did not affect the optical properties arising from intracluster transitions, the pyridylethynyl-bearing clusters (4-6) exhibited reversible visible absorption and photoluminescence responses to protonation/deprotonation events of the terminal pyridyl moieties. The chromism behaviors and proton-binding constants of these clusters were highly dependent on the relative position of the pyridine nitrogen atom, such that the 2-pyridyl (4) and 4-pyridyl (6) isomers showed more pronounced responses than the 3-pyridyl isomer (5). These results suggest that the resonance-coupled movement of the positive charge upon protonation is involved in the optical responses, where the formation of extended charged resonance structures causes significant perturbation effects on the electronic properties of the Au8 unit and also contributes to the high binding affinities. [ABSTRACT FROM AUTHOR]

Enzymes are mainly extracted from the culture broth of microorganisms. Various commercially available enzyme preparations (EPs) are derived from different microorganisms, and the source of the EP should be the same as that mentioned in the manufacture's information. The development of analytical methods that can determine the origin of the final products is important for ensuring that the EPs are nontoxic, especially when used as food additives. In this study, various EPs were subjected to SDS-PAGE, and the main protein bands were excised. After in-gel digestion, the generated peptides were analysed using MALDI-TOF MS, and protein identification was performed by searching the set of peptide masses against protein databases. In total, 36 EPs including amylase, β-galactosidase, cellulase, hemicellulase and protease were analysed, and the information about the enzyme sources was obtained for 30 EPs. Among these, the biological sources determined for 25 EPs were consistent with the manufacturer's information; for the remaining five, enzymes produced by closely-related species were shown as matching proteins due to high sequence similarity. Six enzymes derived from four microorganisms could not be identified because their protein sequences were not registered in the database. As these databases are expanded, this approach of using SDS-PAGE and peptide mass fingerprinting (PMF) can determine the biological origin of enzymes rapidly and contribute to ensuring the safety of EPs. [ABSTRACT FROM AUTHOR]

Transposable elements, including short interspersed repetitive elements (SINEs), comprise nearly half the mammalian genome. Moreover, they are a major source of conserved non-coding elements (CNEs), which play important functional roles in regulating development-related genes, such as enhancing and silencing, serving for the diversification of morphological and physiological features among species. We previously reported a novel SINE family, AmnSINE1, as part of mammalian-specific CNEs. One AmnSINE1 locus, named AS071, showed an enhancer property in the developing mouse diencephalon. Indeed, AS071 appears to recapitulate the expression of diencephalic fibroblast growth factor 8 (Fgf8). Here we established three independent lines of AS071-transgenic mice and performed detailed expression profiling of AS071-enhanced lacZ in comparison with that of Fgf8 across embryonic stages. We demonstrate that AS071 is a distal enhancer that directs Fgf8 expression in the developing diencephalon. Furthermore, enhancer assays with constructs encoding partially deleted AS071 sequence revealed a unique modular organization in which AS071 contains at least three functionally distinct sub-elements that cooperatively direct the enhancer activity in three diencephalic domains, namely the dorsal midline and the lateral wall of the diencephalon, and the ventral midline of the hypothalamus. Interestingly, the AmnSINE1-derived sub-element was found to specify the enhancer activity to the ventral midline of the hypothalamus. To our knowledge, this is the first discovery of an enhancer element that could be separated into respective sub-elements that determine regional specificity and/or the core enhancing activity. These results potentiate our understanding of the evolution of retroposon-derived cis-regulatory elements as well as the basis for future studies of the molecular mechanism underlying the determination of domain- specificity of an enhancer. [ABSTRACT FROM AUTHOR]

Sphingosine-1-phosphate (S1P), a sphingolipid metabolite that is produced inside the cells, regulates a variety of physiological and pathological responses via S1P receptors (S1P1-5). Signal transduction between cells consists of three steps; the synthesis of signaling molecules, their export to the extracellular space and their recognition by receptors. An S1P concentration gradient is essential for the migration of various cell types that express S1P receptors, such as lymphocytes, pre-osteoclasts, cancer cells and endothelial cells. To maintain this concentration gradient, plasma S1P concentration must be at a higher level. However, little is known about the molecular mechanism by which S1P is supplied to extracellular environments such as blood plasma. Here, we show that SPNS2 functions as an S1P transporter in vascular endothelial cells but not in erythrocytes and platelets. Moreover, the plasma S1P concentration of SPNS2-deficient mice was reduced to approximately 60% of wild-type, and SPNS2-deficient mice were lymphopenic. Our results demonstrate that SPNS2 is the first physiological S1P transporter in mammals and is a key determinant of lymphocyte egress from the thymus. [ABSTRACT FROM AUTHOR]

We aimed to detect physiological characteristics that clearly varied among the closely-related Cladosporium sphaerospermum-like species. We isolated the fungi identified as C. sphaerospermum s.l. based on traditional morphological criteria from various locations and substrata, and redefined this initial identification by the molecular phylogenetic methods. The isolates were identified as only C. sphaerospermum and C. halotolerans. We analyzed the substrate-utilization of 95 carbon sources using the Biolog system and made statistical comparisons of isolates by their abilities to grow at different osmolarities. The substrate-utilization patterns separated the isolates into two groups corresponding to the molecular data, and the osmotolerance was different between the species. We first showed that C. sphaerospermum and C. halotolerans were diverse not only at the molecular level but also at the ecological and the physiological levels, by analyzing substrate-utilization patterns and osmotolerance. Furthermore, we showed the potential utility of the Biolog system for discriminating among closely-related fugal species. [ABSTRACT FROM AUTHOR]

Obesity and insulin resistance, the key features of metabolic syndrome, are closely associated with a state of chronic, lowgrade inflammation characterized by abnormal macrophage infiltration into adipose tissues. Although it has been reported that chemokines promote leukocyte migration by activating class lB phosphoinositide-3 kinase (PI3K7) in inflammatory states, little is known about the role of PI3Kγ in obesity-induced macrophage infiltration into tissues, systemic inflammation, and the development of insulin resistance. In the present study, we used murine models of both diet-induced and genetically induced obesity to examine the role of Pi3Kγ in the accumulation of tissue macrophages and the development of obesity-induced insulin resistance. Mice lacking pilOy (Pik3cg-1-), the catalytic subunit of PI3Ky, exhibited improved systemic insulin sensitivity with enhanced insulin signaling in the tissues of obese animals. In adipose tissues and livers of obese Pik3cg' mice, the numbers of infiltrated proinflammatory macrophages were markedly reduced, leading to suppression of inflammatory reactions in these tissues. Furthermore, bone marrow-specific deletion and pharmacological blockade of Pi3Kγ also ameliorated obesity-induced macrophage infiltration and insulin resistance. These data suggest that Pi3Kγ plays a crucial role in the development of both obesity-induced inflammation and systemic insulin resistance and that Pi3K&#x03B3 can be a therapeutic target for type 2 diabetes. [ABSTRACT FROM AUTHOR]

FTY720 is a novel immunomodulating drug that can be phosphorylated inside cells; its phosphorylated form, FTY720-P, binds to a sphingosine 1-phosphate (S1P) receptor, S1P1, and inhibits lymphocyte egress into the circulating blood. Although the importance of its pharmacological action has been well recognized, little is known about how FTY720-P is released from cells after its phosphorylation inside cells. Previously, we showed that zebrafish Spns2 can act as an S1P exporter from cells and is essential for zebrafish heart formation. Here, we demonstrate that human SPNS2 can transport several SiP analogues, including FTY720-P. Moreover, FTY720-P is transported by SPNS2 through the same pathway as S1P. This is the first identification of an FTY720-P transporter in cells; this finding is important for understanding FTY720 metabolism. [ABSTRACT FROM AUTHOR]

Developing a theory of bisimulation in higher-order languages can be hard. Particularly challenging can be: (1) the proof of congruence, as well as enhancements of the bisimulation proof method with "up-to context" techniques, and (2) obtaining definitions and results that scale to languages with different features. To meet these challenges, we present environment bisimulations, a form of bisimulation for higher-order languages, and its basic theory. We consider four representative calculi: pure λ-calculi (call-by-name and call-by-value), call-by-value λ-calculus with higher-order store, and then Higher-Order p-calculus. In each case: we present the basic properties of environment bisimilarity, including congruence; we show that it coincides with contextual equivalence; we develop some up to techniques, including up-to context, as examples of possible enhancements of the associated bisimulation method. Unlike previous approaches (such as applicative bisimulations, logical relations, Sumii-Pierce-Koutavas-Wand), our method does not require induction/indices on evaluation derivation/steps (which may complicate the proofs of congruence, transitivity, and the combination with up-to techniques), or sophisticated methods such as Howe's for proving congruence. It also scales from the pure λ-calculi to the richer calculi with simple congruence proofs. [ABSTRACT FROM AUTHOR]

We propose a type system for lock-freedom in the p-calculus, which guarantees that certain communications will eventually succeed. Distinguishing features of our type system are: it can verify lock-freedom of concurrent programs that have sophisticated recursive communication structures; it can be fully automated; it is hybrid, in that it combines a type system for lock-freedom with local reasoning about deadlock-freedom, termination, and confluence analyses. Moreover, the type system is parameterized by deadlock-freedom/termination/confluence analyses, so that any methods (e.g. type systems and model checking) can be used for those analyses. A lock-freedom analysis tool has been implemented based on the proposed type system, and tested for nontrivial programs. [ABSTRACT FROM AUTHOR]

Sphingosine 1-phosphate (SIP) is a bioactive lipid signal transmitter present in blood. Blood plasma SIP is supplied from erythrocytes and plays an important role in lymphocyte egress from lymphoid organs. However, the SIP export mechanism from erythrocytes to blood plasma is not well defined. To elucidate the mechanism of SIP export from erythrocytes, we performed the enzymatic characterization of SIP transporter in rat erythrocytes. Rat erythrocytes constitutively released SIP without any stimulus. The SIP release was reduced by an ABCA1 transporter inhibitor, glyburide, but not by a multidrug resistance-associated protein inhibitor, MK571, or a multidrug resistance protein inhibitor, cyclosporine A. Furthermore, we measured SIP transport activity using rat erythrocyte insideout membrane vesicles (IOVs). Although the effective SIP transport into IOVs was observed in the presence of ATP, this activity was also supported by dATP and adenosine 5'-(β, γ-imido)triphosphate. The rate of SlP transport increased depending on SIP concentration, with an apparent Km value of 21 μM. Two phosphorylated sphingolipids, dihydrosphingosine 1-phosphate and ceramide 1-phosphate, did not inhibit SIP transport. Similar to the intact erythrocytes, the uptake of SIP into IOVs was inhibited by glyburide and vanadate but not by the other ABC transporter inhibitors. These results suggest that SIP is exported from the erythrocytes by a novel ATP-dependent transporter. [ABSTRACT FROM AUTHOR]

Abstract: Lake Victoria harbors hundreds of cichlid species, which have aggressively developed their morphological features through their evolution. In particular, the shapes of jaws and teeth have diverged markedly, and correlate with feeding ecology. These species are believed to have explosively arisen within the last 15,000 years and are therefore of particular interest to evolutionary biologists. Previously, we reported expressed sequence tags (ESTs) from two cichlid species, Haplochromis chilotes and H. sp. “redtailsheller”, and provided a comparative EST analysis. In this study, we further examined the molecular basis for diversification of Lake Victoria cichlids by generating EST from another cichlid species, H. sp. “Matumbi hunter”; 9,219 clones were applied for sequence determination and 16,795 sequences were newly obtained from this EST set. Comparative analysis of the 68 genes common to the three cichlid species revealed that the degrees of genetic distance and the degrees of genetic polymorphism were highly similar for each pair-wise comparison, suggesting that the protein coding regions of the three cichlid genomes are essentially the same. Because the three species used for the comparative analysis were particularly diverged from each other in morphological and also ecological features, we concluded that the uniformity of transcript sequences among cichlid species in Lake Victoria is a global feature. [Copyright &y& Elsevier]

Abstract: The trace equivalence of BPP was shown to be undecidable by Hirshfeld. We show that all the preorders and equivalences except bisimulation in Glabbeek’s linear time-branching time spectrum are undecidable for BPP. The results are obtained by extending Hirshfeld’s encoding of Minsky machines into BPP. We also show that those preorders and equivalences are undecidable even for a restriction of BPP to 2-labels. [Copyright &y& Elsevier]

Abstract: The objective was to optimize and evaluate the in vivo activities of our novel bifunctional peptide inhibitor (BPI), which alters immune response in autoimmune diseases by modulating the immunological synapse formation. Previously, we have designed PLP-BPI and GAD-BPI by conjugating myelin proteolipid protein (PLP)139–151 and glutamic acid decarboxylase (GAD)208–217, respectively, with CD11a237–246 via a spacer peptide. PLP-BPI and GAD-BPI suppressed the disease progression in experimental autoimmune encephalomyelitis (EAE) and in type-1 diabetes, respectively. In this study, various PLP-BPI derivatives were synthesized and evaluated in the EAE model. Intravenous injections of PLP-BPI derivatives prevented the disease progression more efficiently than did unmodified PLP-BPI. Production of IL-17, a potent proinflammatory cytokine found commonly among MS patients, was significantly low in Ac-PLP-BPI-NH2-2-treated mice. Treatment given after the disease onset could dramatically ameliorate the disease. BPI induced anaphylactic responses at a lower incidence than PLP139–151. In conclusion, PLP-BPI derivatives can effectively suppress the disease severity and morbidity of EAE by post-onset therapeutic treatment as well as prophylactic use. [Copyright &y& Elsevier]

Abstract: The identification of HIV-1 cytotoxic T lymphocyte (CTL) epitopes presented by each HLA allele and the characterization of their CTL responses are important for the study of pathogenesis of AIDS and the development of a vaccine against it. In the present study, we focused on identification and characterization of HIV-1 epitopes presented by HLA-B*5401, which is frequently found in the Asian population, because these epitopes have not yet been reported. We identified these epitopes by using 17-mer overlapping peptides derived from HIV-1 Gag, Pol, and Nef. Seven of these 17-mer peptides induced HLA-B*5401-restricted CD8+ T cell responses. Only five HLA-B*5401-restricted Pol- or Nef-specific CD8+ T cell responses were detected in the analysis using 11-mer overlapping peptides. Three Pol and two Nef optimal peptides were identified by further analysis using truncated peptides. These epitope-specific CTLs effectively killed HLA-B*5401-expressing target cells infected with HIV-1 recombinant vaccinia virus, indicating that these peptides were naturally processed by HLA-B*5401 in HIV-1-infected cells. These epitope-specific CD8+ T cells were elicited in more than 25% of chronically HIV-1-infected individuals carrying HLA-B*5401. Therefore, these epitopes should prove useful for studying the pathogenesis of AIDS in Asia and developing a vaccine against HIV-1. [Copyright &y& Elsevier]

Agonism of peroxisome proliferator-activated receptor (PPAR) a, a key regulator of lipid metabolism, leads to amelioration of lipid abnormalities in dyslipidemic patients. However, whether PPARa agonism is an effective form of therapy for obesity-related insulin resistance associated with lipid abnormalities is unclear. The present study investigated the effects of a potent and subtype-selective PPARct agonist, KRP-lol, in a nonrodent insulin-resistant animal model under pair-fed conditions. Beagle dogs were fed a high-fat diet for 24 wk to induce insulin resistance. During the final 12 wk, 0.03 mgkg~.day~ KRP-I0I (n = 5) or vehicle (n = 5) was administered orally once a day. KRP-l0l administration resulted in a significantly lower weight of overall visceral fat, which is associated with increased adiponectin and decreased leptin in serum. KRP-lOl administration improved hyperglycemia and hyperinsulinemia as well as dyslipidemia in dogs fed a high-fat diet. Oral glucose tolerance test showed that KRP-I0I administration improved glucose intolerance. The KRP-lOl group showed a markedly lower hepatic triglyceride concentration. Lipid oxidation was increased in the liver and skeletal muscles of the KRP-l0l group. These findings in the dog model suggest that the use of potent and subtype-selective PPARcS agonists as a potentially relevant therapeutic approach to treat human insulin resistance associated with visceral obesity. [ABSTRACT FROM AUTHOR]

A bytecode verifier for the Java virtual machine language (JVML) statically checks that hytecode does not cause any fatal error. However, the present verifier does not check correctness of the usage of lock primitives. To solve this problem, we extend Stata and Abadi's type system for JVML by augmenting types with information about how each object is locked and unlocked. The resulting type system guarantees that when a thread terminates, it has released all the locks it has acquired and that a thread releases a lock only if it has acquired the lock previously. We have implemented a prototype Java bytecode verifier based on the type system. We have tested the verifier for several classes in the Java run time library and confirmed that the verifier runs efficiently and gives correct answers. [ABSTRACT FROM AUTHOR]

Abstract: Diacylglycerol kinase (DGK) plays a pivotal role in cellular signal transduction through regulating levels of the second messenger diacylglycerol (DG). Previous studies have revealed that DGK is composed of a family of isozymes that show remarkable heterogeneity in terms of molecular structure, functional domains, tissue and cellular gene expression. Recently, it has been shown that DG is produced in various subcellular compartments including the plasma membrane, internal membranes, cytoskeleton, and nucleus. However, it remains unclear how DG is regulated at distinct subcellular sites. To address this point, we have used an epitope-tag expression system in cultured cells and investigated the subcellular localization of DGK isozymes under the same experimental conditions. We show here that DGK isozymes are targeted differentially to unique subcellular sites in transfected COS7 cells, including the cytoplasm, actin stress fibers, Golgi complex, endoplasmic reticulum, and nucleus. It is also shown that among the isozymes overexpression of DGKβ causes fragmentation of actin stress fibers while a kinase-dead mutant of DGKβ abolishes its colocalization with actin stress fibers. These data strongly suggest that each isozyme may be responsible for the metabolism of DG that is produced upon stimulation at a different and specific subcellular site and that DGKβ activity might have effects on the reorganization of actin stress fibers in transfected COS7 cells. [Copyright &y& Elsevier]

We developed a new method to calculate normal modes of the Earth and planets. It can treat anelasticity directly as imaginary parts of elastic constants and leaky modes due to the open boundary condition set at the upper atmosphere. The eigenvalue problem is described in complex numbers. It is formulated based on a similar treatment of the global matrix governing the system of oscillations to that in the Henyey-type relaxation method used in solar seismology. In our method, the complex eigenvalue problem of a large system is reduced to an eigenvalue problem of a quite small size matrix. The eigenvalue of the small problem is a correction of an assumed complex eigenfrequency and components of the eigenvector are values of eigenfunctions at the outer boundary. Starting from an arbitrary complex frequency around the eigenfrequency of a target mode, we can arrive there within, at most, a dozen of steps of iterative calculations. We compared the results of our method with those calculated by DISPER80, and found good agreement between them. The rate of convergence of the method depends on the linearity of the correction around the eigenfrequency. A numerical example shows good behaviour of them. Even for a model with an atmosphere in which the fundamental spheroidal mode and the fundamental acoustic mode nearly degenerate, we can easily reach the eigenfrequency of and distinguish it from that of without any confusion. And we found that the eigenfrequency of calculated for a realistic atmospheric model which varies annually, most approaches the solid mode in August. The behaviour of can be interpreted with the aid of an acoustic potential which characterizes vertical propagation of sound waves. In addition to the efficiency in the convergence to the eigenfrequencies, numerical tests show strong numerical stability of the method. It stems from the stability in the relaxation method because of the similarity in algebraic structure. For those reasons, we propose the method as an efficient way in calculating synthetic sesimograms, barograms and ionograms for recently observed phenomena relating with coupling between the solid earth, the oceans and the atmosphere. [ABSTRACT FROM AUTHOR]

In order to obtain a design guideline related to the optimum allocation of decoupling capacitor to reduce unwanted electromagnetic wave radiation due to voltage variation and to supply the charge needed for chip operation in a multilayered printed circuit board, the equivalent inductance of the power distribution system is quantitatively analyzed. The power distribution system is represented by a two-dimensional equivalent circuit network and is analyzed. It is found that the parasitic inductance becomes smaller as the distance between the power distribution plane and the ground plane decreases. Further, this result is applied to optimum allocation of the capacitor near the LSI power distribution pin for suppression of LSI malfunctions and to quantification of the radiation suppression effect of capacitor allocation near the via hole that is generated in the interconnect processing of the signal pattern through the power distribution plane and the ground plane. The relationship of the spacing between the planes to the distance between the power distribution pin and the capacitor is formulated so as to keep the power distribution voltage variations within a certain range. Also formulated is the relationship of the radiation suppression effect to the distance between the via hole and the capacitor location in order to obtain constant radiation suppression efficiency. In this way, specific design values of capacitor allocation are obtained for suppression of LSI malfunctions and unwanted electromagnetic radiation. © 2006 Wiley Periodicals, Inc. Electron Comm Jpn Pt 2, 89(10): 27–35, 2006; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/ecjb.20154 [ABSTRACT FROM AUTHOR]

Abstract: Lake Victoria harbors more than 300 species of cichlid fish, which are adapted to a variety of ecological niches with various morphological species-specific features. However, it is believed that these species arose explosively within the last 14,000 years and transcripts among Lake Victoria cichlid species are almost identical in sequence. These data prompted us to develop a DNA chip assay to compare patterns of gene expression among cichlid species. We prepared a DNA chip spotted with 6240 elements derived from cichlid expressed sequence tag (EST) clones and successfully characterized gene expression differences between the cichlid species Haplochromis chilotes and Haplochromis sp. “rockkribensis”. We identified 14 transcripts that were differentially expressed between these species at an early developmental stage, 15 days post-fertilization (dpf), and several were further analyzed using quantitative real-time PCR (qPCR). One of these differentially expressed transcripts was a homolog of microfibril-associated glycoprotein 4 (magp4), a putative causative gene for the human inherited disease, Smith–Magenis syndrome (SMS), for which facial defects are among the phenotypic features. Further analysis of magp4 expression showed that magp4 was expressed in the jaw portion of cichlid fry and that expression profiles between Haplochromis chilotes and Haplochromis sp. “rockkribensis” differed during development. These data suggest that the differential expression of a gene associated with human cranial morphogenesis may be involved in the diversification of cichlid jaw morphs. [Copyright &y& Elsevier]

We propose a new type system for information flow analysis for the π-calculus. As demonstrated by recent studies, information about whether each communication succeeds is important for precise information flow analysis for concurrent programs. By collecting such information using ideas of our previous type systems for deadlock/livelock-freedom, our type system can perform more precise analysis for certain communication/synchronization patterns (like synchronization using locks) than previous type systems. Our type system treats a wide range of communication/synchronization primitives in a uniform manner, which enabled development of a clear proof of type soundness and a sound and complete type inference algorithm. [ABSTRACT FROM AUTHOR]

Abstract: To modulate the immune responses of DNA vaccine, it is very important to control the disposition and gene expression of plasmid DNA (pDNA) after local administration. We chose methylated bovine serum albumin (mBSA), a cationic macromolecule, as a carrier of pDNA. We examined the effects of complexation of pDNA with mBSA on the disposition and gene expression in mice after intramuscular administration. The elimination from injection site was retarded and the accumulation to lymph nodes was increased at the positively charged mBSA/pDNA complexes. As the charge ratios of mBSA/pDNA complexes were higher, the levels of gene expression were reduced. Antigen specific immune responses were evaluated using pDNA encoding ovalbumin (OVA), pCMV-OVA, as a model antigen-expressing pDNA. However, significant levels of production of anti-ovalbumin IgG antibody were obtained in mice immunized with a positively charged complex, mBSA/pCMV-OVA (8:1) (weight ratio). In vitro experiments using DC2.4 cells, a murine dendritic cell line, demonstrated that the levels of gene expression and cytokine release were increased by complexation. These results suggest that the immune responses might be manipulated by complexation presumably due to the altered disposition and gene expression of pDNA. [Copyright &y& Elsevier]

Abstract: Hydrodynamics-based gene delivery, involving a large-volume and high-speed intravenous injection of naked plasmid DNA (pDNA), gives a significantly high level of transgene expression in vivo. This has attracted a lot of attention and has been used very frequently as an efficient, simple and convenient transfection method for laboratory animals. Until recently, however, little information has been published on the pharmacokinetics of the injected DNA molecules and of the detailed mechanisms underlying the efficient gene transfer. We and other groups have very recently demonstrated that the mechanism for the hydrodynamics-based gene transfer would involve, in part, the direct cytosolic delivery of pDNA through the cell membrane due to transiently enhanced permeability. Along with the findings in our series of studies, this article reviews the cumulative reports and other intriguing information on the controlled pharmacokinetics of naked pDNA in the hydrodynamics-based gene delivery. In addition, we describe various applications reported so far, as well as the current attempts and proposals to develop novel gene medicines for future gene therapy using the concept of the hydrodynamics-based procedure. Furthermore, the issues associated with the clinical feasibility of its seemingly invasive nature, which is probably the most common concern about this hydrodynamics-based procedure, are discussed along with its future prospects and challenges. [Copyright &y& Elsevier]

It is an important criterion of program correctness that a program accesses resources in a valid manner. For example, a memory region that has been allocated should eventually be deallocated, and after the deallocation, the region should no longer be accessed. A file that has been opened should be eventually closed. So far, most of the methods to analyze this kind of property have been proposed in rather specific contexts (like studies of memory management and verification of usage of lock primitives), and it was not clear what the essence of those methods was or how methods proposed for individual problems are related. To remedy this situation, we formalize a general problem of analyzing resource usage as a resource usage analysis problem, and propose a type-based method as a solution to the problem. [ABSTRACT FROM AUTHOR]

Proinflammatory cytokinemia and subsequent endothelial cell activation are the major pathological features of Kawasaki disease (KD), which progresses to systemic vasculitis and results in coronary artery lesions (CALs). We studied the serum levels of proinflammatory cytokines and of the soluble receptors before and after intravenous gamma-globulin (IVGG) treatment to investigate whether the anti-inflammatory effect of IVGG was due to the reduction of increased serum levels of their cytokines and soluble receptors. In the acute phase of KD, the serum levels of interleukin (IL)-2 and IL-5, as well as those of IL-6, IL-10, and interferon-?, were markedly higher than those in controls. The level of tumor necrosis factor-a was higher than that in the control, but the difference was slight and not significant. The soluble IL-6 receptor levels were lower than those of the controls. After IVGG administration, the increased levels of these cytokines and soluble receptors were abruptly down-regulated to within their normal ranges. The patients enrolled in the present study were all effectively treated with IVGG, without a steroid, and improved without any residual CALs. Overall, IVGG administration to patients with KD was found to be effective in reducing inflammatory processes and in preventing CALs, and was followed by reduction of the serum levels of the proinflammatory cytokines and their receptors. [ABSTRACT FROM AUTHOR]

Abstract: The Lake Victoria Cichlid fishes have diverged very rapidly. The estimated 500 species inhabiting the lake are believed to have arisen within the last 14,000 years. The fishes'' jaws and teeth have diverged markedly to adapt to different feeding behaviors and environments. To examine how the genomes of these fishes differentiated during speciation, we performed comparative analysis of expressed sequenced tag (EST) sequences. We constructed cDNA libraries derived only from the jaw portions of two cichlid species endemic to Lake Victoria. We sequenced 17,280 cDNA clones from Haplochromis chilotes and 9600 cDNA clones from Haplochromis sp. “Redtailsheller” and obtained 543 different genes common to both species. Of these genes, 441 were essentially identical between species and 102 contained base replacements in their open reading frame (ORF) or untranslated (UTR) regions. Comparative analysis of 71selected sequences has revealed that while the degree of polymorphism is 0.0054/site for H. chilotes and 0.0047/site for H. sp. “Redtailsheller”, genetic distance between the two species is 0.0031/site. The genetic distance particularly indicates that the two species diverged about 890,000 years ago. [Copyright &y& Elsevier]

We propose a general, powerful framework of type systems for the π-calculus, and show that we can obtain as its instances a variety of type systems guaranteeing non-trivial properties like deadlock-freedom and race-freedom. A key idea is to express types and type environments as abstract processes: We can check various properties of a process by checking the corresponding properties of its type environment. The framework clarifies the essence of recent complex type systems, and it also enables sharing of a large amount of work such as a proof of type preservation, making it easy to develop new type systems. [Copyright &y& Elsevier]

We have grown a high-crystalline-quality homoepitaxial diamond (001) layer by using microwave plasma chemical vapor deposition. We did not detect any impurities, such as H, B, N and O, in the homoepitaxial layer by secondary ion-mass spectroscopy. The full width at half maximum of the Raman diamond-related peak was as low as 2.35 cm−1. The Raman results showed that in the growth temperature range, Tg, from 650 to 730 °C, local crystalline quality deteriorated with the Tg and that for Tg>730 °C, it improved with the Tg. However, as the Tg was increased to above 780 °C, almost all the surface became covered with unepitaxial crystals, which obstructed hole conduction on the H-terminated surface. Consequently, we obtained high Hall mobility at a Tg''s of approximately 660 and 766 °C. At room temperature, we obtained a Hall mobility of 814 cm2/Vs in the air. [Copyright &y& Elsevier]

Interferons (IFNs) exhibit pleiotropic biological activities that are considered to play important roles in tumor suppression and rejection. Therefore, IFN genes are promising for in vivo cytokine gene therapy targeted against tumors. In the present study, we evaluated the efficacy of hydrodynamics-based IFN gene transfer for tumor treatment, in which the naked pDNA encoding IFN-β or IFN-γ was administered into the tail vein of mice following portal vein (liver metastasis), tail vein (lung metastasis), or subcutaneous injection (subcutaneous tumor) of mouse colon carcinoma CT-26 cells. A substantial amount of IFN was soon markedly expressed in the liver and a transient increase in IFN activity was detected in the circulation. This procedure caused transgene-specific IFN production with little induction of other proinflammatory cytokines. In the liver metastasis experiment, the mice treated with IFN-expressing pDNA displayed a profound reduction in liver metastasis and a prolonged survival. Administration of the pDNA at an earlier stage of metastasis was more crucial for the antitumor effect. Similar tumor suppression was seen in the lung metastasis experiment. These therapeutic effects were more marked with IFN-β-expressing pDNA treatment than with IFN-γ-expressing pDNA treatment. On the other hand, subcutaneous CT-26 tumor growth was hardly affected by pDNA administration. These results suggest that the hydrodynamics-based transfer of naked pDNA is a convenient and efficient method of IFN gene therapy against metastatic tumors. [Copyright &y& Elsevier]

Advanced type systems for the π-calculus have recently been proposed to guarantee deadlock-freedom in the sense that certain communications will eventually succeed unless the whole process diverges. Although such guarantees are useful for reasoning about the behavior of concurrent programs, there still remains the weakness that the success of a communication is not completely guaranteed due to the possibility of divergence. For example, although a server process that has received a request message cannot discard the request, it is allowed to infinitely delegate the request to other processes, causing a livelock. In this paper, we present a type system which guarantees that certain communications will eventually succeed under fair scheduling, regardless of whether processes diverge. We also present a variant of the type system which guarantees that a communication will succeed within a given number of reduction steps. [Copyright &y& Elsevier]