RustHorn: CHC-based Verification for Rust Programs (full version)

Reduction to the satisfiability problem for constrained Horn clauses (CHCs) is a widely studied approach to automated program verification. The current CHC-based methods for pointer-manipulating programs, however, are not very scalable. This paper proposes a novel translation of pointer-manipulating Rust programs into CHCs, which clears away pointers and memories by leveraging ownership. We formalize the translation for a simplified core of Rust and prove its correctness. We have implemented a prototype verifier for a subset of Rust and confirmed the effectiveness of our method.Comment: Full version of the same-titled paper in ESOP202

Borrowable Fractional Ownership Types for Verification

Automated verification of functional correctness of imperative programs with references (a.k.a. pointers) is challenging because of reference aliasing. Ownership types have recently been applied to address this issue, but the existing approaches were limited in that they are effective only for a class of programs whose reference usage follows a certain style. To relax the limitation, we combine the approaches of ConSORT (based on fractional ownership) and RustHorn (based on borrowable ownership), two recent approaches to automated program verification based on ownership types, and propose the notion of borrowable fractional ownership types. We formalize a new type system based on the borrowable fractional ownership types and show how we can use it to automatically reduce the program verification problem for imperative programs with references to that for functional programs without references. We also show the soundness of our type system and the translation, and conduct experiments to confirm the effectiveness of our approach.Comment: An extended version of the paper to appear in Proceedings of VMCAI 202

Detection of Excess Hard X-ray Emission from the Group of Galaxies HCG62

From the group of galaxies HCG62, we detected an excess hard X-ray emission in energies above $\sim 4$ keV with \A SCA. The excess emission is spatially extended up to $\sim10'$ from the group center, and somewhat enhanced toward north. Its spectrum can be represented by either a power-law of photon index 0.8-2.7, or a Bremsstrahlung of temperature $>6.3$ keV. In the 2-10 keV range, the observed hard X-ray flux, $(1.0\pm0.3)\times10^{-12}$ erg cm$^{-2}$ s$^{-1}$, implies a luminosity of $(8.0\pm2.0)\times10^{41}$ erg s$^{-1}$ for a Hubble constant of 50 km s$^{-1}$ Mpc$^{-1}$. The emission is thus too luminous to be attributed to X-ray binaries in the memb er galaxies. We discuss possible origin of the hard X-ray emission.Comment: 6 pages, 3 Postscript figures, uses emulateapj.sty. Accepted for publication in the Astrophysical Journal Letter

A Splice Variant of ASC Regulates IL-1β Release and Aggregates Differently from Intact ASC

The apoptosis-associated speck-like protein containing a caspase recruit domain (ASC) is involved in apoptosis and innate immunity and is a major adaptor molecule responsible for procaspase-1 activation. ASC mRNA is encoded by three exons: exons 1 and 3 encode a pyrin domain (PYD) and caspase recruit domain (CARD), respectively, and exon 2 encodes a proline and glycine-rich (PGR) domain. Here, we identified a variant ASC protein (vASC) lacking the PGR domain that was smaller than full length ASC (fASC) derived from fully transcribed mRNA and searched for differences in biochemical and biological nature. Both fASC and vASC were found to activate procaspase-1 to a similar degree, but the efficiency of IL-1β excretion was significantly higher for vASC. There was also a marked structural difference observed in the fibrous aggregates formed by fASC and vASC. These results suggest that although the PGR domain is dispensable for procaspase-1 activation, it plays an important role in the regulation of the molecular structure and activity of ASC

Phase I clinical trial of the vaccination for the patients with metastatic melanoma using gp100-derived epitope peptide restricted to HLA-A*2402

<p>Abstract</p> <p>Background</p> <p>The tumor associated antigen (TAA) gp100 was one of the first identified and has been used in clinical trials to treat melanoma patients. However, the gp100 epitope peptide restricted to HLA-A*2402 has not been extensively examined clinically due to the ethnic variations. Since it is the most common HLA Class I allele in the Japanese population, we performed a phase I clinical trial of cancer vaccination using the HLA-A*2402 gp100 peptide to treat patients with metastatic melanoma.</p> <p>Methods</p> <p>The phase I clinical protocol to test a HLA-A*2402 gp100 peptide-based cancer vaccine was designed to evaluate safety as the primary endpoint and was approved by The University of Tokyo Institutional Review Board. Information related to the immunologic and antitumor responses were also collected as secondary endpoints. Patients that were HLA-A*2402 positive with stage IV melanoma were enrolled according to the criteria set by the protocol and immunized with a vaccine consisting of epitope peptide (VYFFLPDHL, gp100-in4) emulsified with incomplete Freund's adjuvant (IFA) for the total of 4 times with two week intervals. Prior to each vaccination, peripheral blood mononuclear cells (PBMCs) were separated from the blood and stored at -80°C. The stored PBMCs were thawed and examined for the frequency of the peptide specific T lymphocytes by IFN-γ- ELISPOT and MHC-Dextramer assays.</p> <p>Results</p> <p>No related adverse events greater than grade I were observed in the six patients enrolled in this study. No clinical responses were observed in the enrolled patients although vitiligo was observed after the vaccination in two patients. Promotion of peptide specific immune responses was observed in four patients with ELISPOT assay. Furthermore, a significant increase of CD8⁺gp100-in4⁺CTLs was observed in all patients using the MHC-Dextramer assay. Cytotoxic T lymphocytes (CTLs) clones specific to gp100-in4 were successfully established from the PBMC of some patients and these CTL clones were capable of lysing the melanoma cell line, 888 mel, which endogenously expresses HLA-restricted gp100-in4.</p> <p>Conclusion</p> <p>Our results suggest this HLA-restricted gp100-in4 peptide vaccination protocol was well-tolerated and can induce antigen-specific T-cell responses in multiple patients. Although no objective anti-tumor effects were observed, the effectiveness of this approach can be enhanced with the appropriate modifications.</p

Suzaku Observation of HCG 62: Temperature, Abundance, and Extended Hard X-ray Emission Profiles

We present results of 120 ks observation of a compact group of galaxies HCG~62 ($z=0.0145$) with Suzaku XIS and HXD-PIN\@. The XIS spectra for four annular regions were fitted with two temperature {\it vapec} model with variable abundance, combined with the foreground Galactic component. The Galactic component was constrained to have a common surface brightness among the four annuli, and two temperature {\it apec} model was preferred to single temperature model. We confirmed the multi-temperature nature of the intra-group medium reported with Chandra and XMM-Newton, with a doughnut-like high temperature ring at radii 3.3--6.5$'$ in a hardness image. We found Mg, Si, S, and Fe abundances to be fairly robust. We examined the possible ``high-abundance arc'' at $\sim 2'$ southwest from the center, however Suzaku data did not confirm it. We suspect that it is a misidentification of an excess hot component in this region as the Fe line. Careful background study showed no positive detection of the extended hard X-rays previously reported with ASCA, in 5--12 keV with XIS and 12--40 keV with HXD-PIN, although our upper limit did not exclude the ASCA result. There is an indication that the X-ray intensity in $r<3.3'$ region is $70\pm 19$% higher than the nominal CXB level (5--12 keV), and Chandra and Suzaku data suggest that most of this excess could be due to concentration of hard X-ray sources with an average photon index of $\Gamma=1.38\pm 0.06$. Cumulative mass of O, Fe and Mg in the group gas and the metal mass-to-light ratio were derived and compared with those in other groups. Possible role of AGN or galaxy mergers in this group is also discussed.Comment: 29 pages with 9 figures, accepted for publication in PASJ Vol 60, second Suzaku special issu

Suzaku Observation of the Metallicity in the Interstellar Medium of NGC 4258

The Suzaku X-ray satellite observed the nearby spiral galaxy NGC 4258 for a total good exposure time of 100 ks. We present an analysis of the Suzaku XIS data, in which we confirm that the 0.5--2 keV spectra of the interstellar medium (ISM) are well-represented by a two-temperature model. The cool and hot ISM temperatures are 0.23+-0.02 and 0.59 +-0.01 keV, respectively. Suzaku's excellent spectral sensitivity enables us to measure the metal abundances of O, Ne, Mg, Si and Fe of the ISM for the first time. The resultant abundance pattern of O, Mg, Si, and Fe is consistent with that of the new solar abundance table of Lodders (2003), rather than Anders & Grevesse (1989). This suggests that the metal enrichment processes of NGC 4258 and of our Galaxy are similar.Comment: 9 pages, 4 figure

Suzaku diagnostics of the energetics in the lobes of the giant radio galaxy 3C 35

The Suzaku observation of a giant radio galaxy 3C 35 revealed faint extended X-ray emission, associated with its radio lobes and/or host galaxy. After careful subtraction of the X-ray and non-X-ray background and contaminating X-ray sources, the X-ray spectrum of the faint emission was reproduced by a sum of the power-law (PL) and soft thermal components. The soft component was attributed to the thermal plasma emission from the host galaxy. The photon index of the PL component, $\Gamma = 1.35_{-0.86}^{+0.56}$$_{-0.10}^{+0.11}$ where the first and second errors represent the statistical and systematic ones, was found to agree with the synchrotron radio index from the lobes, $\Gamma_{\rm R} = 1.7$. Thus, the PL component was attributed to the inverse Compton (IC) X-rays from the synchrotron electrons in the lobes. The X-ray flux density at 1 keV was derived as $13.6\pm 5.4_{-3.6}^{+4.0}$ nJy with the photon index fixed at the radio value. The X-ray surface brightness from these lobes ($\sim 0.2$ nJy arcmin$^{-2}$) is lowest among the lobes studied through the IC X-ray emission. In combination with the synchrotron radio flux density, $7.5 \pm 0.2$ Jy at 327.4 MHz, the electron energy density spatially averaged over the lobes was evaluated to be the lowest among those radio galaxies, as $u_{\rm e} = (5.8 \pm 2.3 _{-1.7}^{+1.9}) \times 10^{-14}$ ergs cm$^{-3}$ over the electron Lorentz factor of $10^{3}$ -- $10^{5}$. The magnetic energy density was calculated as $u_{\rm m}=(3.1_{-1.0}^{+2.5}$$_{-0.9}^{+1.4}) \times 10^{-14}$ ergs cm$^{-3}$, corresponding to the magnetic field strength of $0.88_{-0.16}^{+0.31}$$_{-0.14}^{+0.19}$ $\mu$G. These results suggest that the energetics in the 3C 35 lobes are nearly consistent with equipartition between the electrons and magnetic fields.Comment: 10 pages, 8 figures, accepted for Ap

J-CKD-DB: a nationwide multicentre electronic health record-based chronic kidney disease database in Japan

The Japan Chronic Kidney Disease (CKD) Database (J-CKD-DB) is a large-scale, nation-wide registry based on electronic health record (EHR) data from participating university hospitals. Using a standardized exchangeable information storage, the J-CKD-DB succeeded to efficiently collect clinical data of CKD patients across hospitals despite their different EHR systems. CKD was defined as dipstick proteinuria ≥1+ and/or estimated glomerular filtration rate <60 mL/min/1.73 m² base on both out- and inpatient laboratory data. As an initial analysis, we analyzed 39, 121 CKD outpatients (median age was 71 years, 54.7% were men, median eGFR was 51.3 mL/min/1.73 m²) and observed that the number of patients with a CKD stage G1, G2, G3a, G3b, G4 and G5 were 1, 001 (2.6%), 2, 612 (6.7%), 23, 333 (59.6%), 8, 357 (21.4%), 2, 710 (6.9%) and 1, 108 (2.8%), respectively. According to the KDIGO risk classification, there were 30.1% and 25.5% of male and female patients with CKD at very high-risk, respectively. As the information from every clinical encounter from those participating hospitals will be continuously updated with an anonymized patient ID, the J-CKD-DB will be a dynamic registry of Japanese CKD patients by expanding and linking with other existing databases and a platform for a number of cross-sectional and prospective analyses to answer important clinical questions in CKD care