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Sodium–glucose co-transporter-2 (SGLT2) inhibitors reduce progression of chronic kidney disease and the risk of cardiovascular morbidity and mortality in a wide range of patients. However, their effects on kidney disease progression in some patients with chronic kidney disease are unclear because few clinical kidney outcomes occurred among such patients in the completed trials. In particular, some guidelines stratify their level of recommendation about who should be treated with SGLT2 inhibitors based on diabetes status and albuminuria. We aimed to assess the effects of empagliflozin on progression of chronic kidney disease both overall and among specific types of participants in the EMPA-KIDNEY trial.

The EMPA-KIDNEY trial showed that empagliflozin reduced the risk of the primary composite outcome of kidney disease progression or cardiovascular death in patients with chronic kidney disease mainly through slowing progression. We aimed to assess how effects of empagliflozin might differ by primary kidney disease across its broad population.

Mountains are the water towers of the world, supplying a substantial part of both natural and anthropogenic water demands1,2. They are highly sensitive and prone to climate change3,4, yet their importance and vulnerability have not been quantified at the global scale. Here we present a global water tower index (WTI), which ranks all water towers in terms of their water-supplying role and the downstream dependence of ecosystems and society. For each water tower, we assess its vulnerability related to water stress, governance, hydropolitical tension and future climatic and socio-economic changes. We conclude that the most important (highest WTI) water towers are also among the most vulnerable, and that climatic and socio-economic changes will affect them profoundly. This could negatively impact 1.9 billion people living in (0.3 billion) or directly downstream of (1.6 billion) mountainous areas. Immediate action is required to safeguard the future of the world’s most important and vulnerable water towers.

During the 2020–2021 winter season, we detected 6 gamma‐ray glows at Kanazawa University, Japan. Negative surface electric fields (E‐fields; in the sign convention of atmospheric electricity) were observed by a field mill during all the glow cases. In five of the six cases, the peak E‐field reached around −12 kV m−1, and the E‐field during the glow detection was the strongest in the interval including 3 hr before and after the detection time. Therefore, negative charges should have been dominant in the thunderclouds that produced the gamma‐ray glows, and electrons were probably accelerated and multiplied by the E‐fields between a predominantly negative charge layer and a localized positive charge layer below. In addition, we extracted 8 non‐detection cases in the 2020–2021 winter season, in which surface E‐fields were stronger than −12 kV m−1. In 5 of the 8 cases, radar echoes were inadequately developed, suggesting insufficient charge accumulation. On the other hand, the remaining 3 cases had well‐developed radar echoes, and there was no significant difference from the detection cases. Gamma‐ray glow is a minute‐lasting burst of high‐energy photons associated with thunderclouds. High‐energy photons are considered to originate from high‐energy electrons accelerated and multiplied in strong electric fields inside thunderclouds. When a gamma‐ray glow is detected on the ground, electrons are considered to be accelerated downward by upward electric fields. In the 2020–2021 winter season, we detected a total of 6 gamma‐ray glows during winter thunderstorms at Kanazawa University, Japan. An electric‐field monitor recorded negative electric fields at the surface during all the glow detections, indicating negative charges overhead. It suggests that the thunderclouds that produced the gamma‐ray glows were strongly charged negatively, and a localized positive charge layer existed in the lower part to produce an upward electric field for downward electron acceleration. In the 2020–2021 winter season, 6 gamma‐ray glows were detected at Kanazawa University, Japan, with electric‐field measurementSurface electric fields were negative during the detection of all the gamma‐ray glowsHigh‐energy electrons seemed to be produced between a well‐developed negative charge region and a localized positive charge region below In the 2020–2021 winter season, 6 gamma‐ray glows were detected at Kanazawa University, Japan, with electric‐field measurement Surface electric fields were negative during the detection of all the gamma‐ray glows High‐energy electrons seemed to be produced between a well‐developed negative charge region and a localized positive charge region below

Relativistic Runaway Electrons Avalanches (RREAs) development depends on the applied electric field and the environment's air density. This dependency controls the RREA exponential growth length scale. The RREA development affects the bremsstrahlung excess occurring due to the passage of charged particles through the thundercloud's electric fields, the gamma‐ray glow. We used Monte Carlo simulations to develop an empirical model showing the RREA behavior in a realistic atmospheric density profile. The new formulation shows how the density variation modulates the electron population under electric field strengths near the RREA electric field threshold. The model limits the initial RREA altitude range as a function of the electric field strength. The new model is valid between ∼0.6 and ∼18 km, covering the relevant heights to investigate the generation of ground‐detected gamma‐ray glows. Thunderclouds are energy sources for trespassing charged particles from cosmic rays. This extra energy gain may induce electron avalanches, known as Relativistic Runaway Electron Avalanches (RREAs), resulting in an enhanced gamma‐ray flux via bremsstrahlung, the gamma‐ray glow. Recent studies relate this enhancement to electric field strengths close to the RREA requirement. The atmospheric density variations affect avalanche development by modifying the RREA requirement, resulting in isolated avalanches by imposing limits to the avalanche's initial altitude. We show how RREAs develop in a realistic atmospheric density profile. We present a modification on the characteristic avalanche length under this condition. The initial avalanche altitude is crucial because it completely modifies the density profile trespassed by a downward electron shower. Finally, we discuss the consequences of isolated RREAs for high‐energy emissions and show that the electric field strength constrains the possible initial altitudes for the gamma‐ray glow. A new empirical model quantifies how electron avalanches vanish because of atmospheric density variations with ∼10% accuracyThe model limits the initial altitude of electron avalanche development for electric field strengths near the avalanche thresholdWe narrow the possible gamma‐ray glow source height range with the new model which is valid through ∼0.6–18 km A new empirical model quantifies how electron avalanches vanish because of atmospheric density variations with ∼10% accuracy The model limits the initial altitude of electron avalanche development for electric field strengths near the avalanche threshold We narrow the possible gamma‐ray glow source height range with the new model which is valid through ∼0.6–18 km

A gamma‐ray glow, a minute‐lasting burst of high‐energy photons from a thundercloud, was detected by ground‐based apparatus at Kanazawa University, Japan, in a winter thunderstorm on 18 December 2018. The gamma‐ray glow was quenched by a lightning flash within a brief time window of 40 ms. The lightning flash produced several low‐frequency (LF) E‐change pulses that were temporally coincident with the termination of the gamma‐ray glow, and that were located within 0.5 km from the observation site by the Fast Antenna Lightning Mapping Array. The LF pulses had the same polarity as a positive cloud‐to‐ground current and a normal‐polarity in‐cloud current. Since this polarity is against the upward electric field for producing the gamma‐ray glow (accelerating electrons to the ground), we infer that the glow was terminated by a normal‐polarity in‐cloud discharge activity between a middle negative layer and an upper positive layer. Strong electric fields inside thunderclouds may accelerate electrons to relativistic energy, and cause a burst of high‐energy photons called gamma‐ray glow. Gamma‐ray glows are sometimes terminated with a lightning flash as it discharges electric fields responsible for electron acceleration. In this study, we observed the termination of a gamma‐ray glow with a detailed lightning mapping observation in the radio‐frequency band. An in‐cloud lightning flash between two charge layers inside a thundercloud reduced an electric field that accelerated electrons. Radio‐frequency observations of glow termination are a powerful tool to investigate the charge structure associated with electron acceleration. A gamma‐ray glow was terminated by a lightning flash within a brief time window of 40 msPositive‐polarity low‐frequency pulses were located within 0.5 km of the detection siteThe glow was ceased by a normal‐polarity in‐cloud discharge activity between a middle negative layer and an upper positive layer A gamma‐ray glow was terminated by a lightning flash within a brief time window of 40 ms Positive‐polarity low‐frequency pulses were located within 0.5 km of the detection site The glow was ceased by a normal‐polarity in‐cloud discharge activity between a middle negative layer and an upper positive layer

An on‐ground observation program for high‐energy atmospheric phenomena in winter thunderstorms along the Japan Sea has been performed via measurements of gamma ray radiation, atmospheric electric field, and low‐frequency radio band. On 11 February 2017, the radiation detectors recorded gamma ray emission lasting for 75 s, and then abruptly terminated with a nearby lightning discharge. The gamma ray spectrum extended up to 20 MeV and was reproduced by a cutoff power law model with a photon index of 1.36−0.04+0.03, being consistent with Bremsstrahlung radiation from a thundercloud (known as a gamma‐ray glow or a thunderstorm ground enhancement). The low‐frequency radio monitors, installed ∼50 km away from the gamma ray observation site recorded leader development of an intracloud/intercloud discharge spreading over ∼60 km area with a ∼300‐ms duration. The timing of the gamma ray termination coincided with the moment when the leader development of the intracloud/intercloud discharge passed 0.7 km horizontally away from the radiation monitors. The intracloud/intercloud discharge started ∼15 km away from the gamma ray observation site. Therefore, the glow was terminated by the leader development, while it did not trigger the lightning discharge in the present case. This study presents high‐energy radiation, atmospheric electric field and low‐frequency radio measurements of winter thunderstorms in Japan. Long‐duration gamma ray bursts, called “gamma ray glows,” are thought to originate from electrons accelerated and multiplied by strong electric fields in thunderclouds. There are unsolved questions such as electron‐acceleration mechanisms, position of the acceleration site, lifetime, and life cycle of the bursts. We observed a gamma ray burst lasting for ∼75 s from a thundercloud abruptly terminated with a lightning discharge. The gamma ray source was destroyed by a cloud‐to‐cloud discharge over the gamma ray observation site but not related to the triggering of the discharge in the present case. A gamma ray glow and its termination with a lightning discharge was observed in a Japanese winter thunderstormThe glow was terminated by leader development of a horizontally long intracloud/intercloud discharge passing nearby overheadThe intracloud/intercloud discharge was not triggered by the glow in the present case because it started far from the gamma ray glow site

Seven subunits of the mitochondrial contact site and cristae junction (CJ) organizing system (MICOS) in humans have been recently described in function and structure. QIL1 (also named MIC13) is a small complex that is crucial for the maintenance and assembling of MICOS. A novel mutation of an essential splice site in the C19orf70gene encoding QIL1 induces severe mitochondrial encephalopathy, hepatopathy and lactate acidosis consistent with psychomotor retardation. In addition, bilateral kidney stones were observed. Disassembly of MICOS complex subunits displays lack of MIC10-MIC26-MIC27-QIL1 subcomplex, resulting in aberrant cristae structure and a loss of cristae junctions and contact sites. In liver and muscle tissue, the activity of the respiratory chain complexes (OXPHOS) was severely impaired. Defects in MICOS complex do not only affect mitochondrial architecture, but also mitochondrial fusion, metabolic signalling, lipid trafficking and cellular electric homeostasis.

Oligonucleotides are key elements of nucleic acid therapeutics such as small interfering RNAs (siRNAs). Influenza and Ebolaviruses are zoonotic RNA viruses mutating very rapidly, and their sequence changes must be characterized intensively to design therapeutic oligonucleotides with long utility. Focusing on a total of 182 experimentally validated siRNAs for influenza A, B and Ebolaviruses compiled by the siRNA database, we conducted time-series analyses of occurrences of siRNA targets in these viral genomes. Reflecting their high mutation rates, occurrences of target oligonucleotides evidently fluctuate in viral populations and often disappear. Time-series analysis of the one-base changed sequences derived from each original target identified the oligonucleotide that shows a compensatory increase and will potentially become the ‘awaiting-type oligonucleotide’; the combined use of this oligonucleotide with the original can provide therapeutics with long utility. This strategy is also useful for assigning diagnostic reverse transcription-PCR primers with long utility.

Electric field of thunderclouds modifies components and energy spectra of the cosmic‐ray air shower. In particular, thunderstorms accelerate charged particles, resulting in an enhancement of gamma‐ray fluxes on the ground, known as a gamma‐ray glow. This phenomenon has been observed in recent years by the Gamma‐Ray Observation of Winter THunderclouds collaboration from winter thunderstorms in the Hokuriku area of Japan. The present work examines the ambient conditions required to produce spectral features of the previously detected gamma‐ray glows, by using Monte Carlo simulations of particle interactions in the atmosphere. We focus on three parameters, the strength and length of the electric field, and the length of a null‐field attenuation region below the electrified region. The average spectrum of observed gamma‐ray glows in winter thunderstorms of Japan requires an electric field intensity close to 0.31 MV/m, slightly exceeding the Relativistic Runaway Electron Avalanche threshold of 0.284 MV/m. The vertical size of the electric field region should be comparable to 1 km. The estimated attenuation region size is 300–500 m, necessary to reduce the low‐energy photon flux of the average gamma‐ray glows. There is still a wide range of acceptable parameter sets with degeneracy to make a similar spectrum. Thunderclouds modify the incident cosmic‐ray flux due to their electric field. In particular, thunderstorms accelerate charged particles inducing enhancement of the gamma‐ray flux at the ground, known as the gamma‐ray glow. Throughout recent years, the community observes gamma‐ray glows on the Japanese Hokuriku coast. This paper examines the ambient conditions required to produce the characteristic gamma‐ray glow spectrum using Monte Carlo simulation. We focus on the electric field strength, and electric field length and introduced a null‐field attenuation region following previously reported features of Japanese winter thunderclouds. We conclude that most observed gamma‐ray glows at the Hokuriku region require electric fields close to 0.32 MV/m along approximately 1 km and an attenuation region of 300–500 m to reproduce the observations. Finally, the three studied variables can be differently combined to generate similar spectra regarding a space of phase of three coordinates being electric field strength, electric field length, and attenuation space length. We use Monte Carlo simulations of electron and gamma‐ray interactions in thunderstorms to explain observed gamma‐ray glowsWe successfully simulated gamma‐ray glow spectra and extracted an acceptable set of ambient atmospheric factors of the glowFit configurations have electric fields as ∼0.30 MV/m with a ∼1 km size scale and a null field region of ∼0.5 km below that We use Monte Carlo simulations of electron and gamma‐ray interactions in thunderstorms to explain observed gamma‐ray glows We successfully simulated gamma‐ray glow spectra and extracted an acceptable set of ambient atmospheric factors of the glow Fit configurations have electric fields as ∼0.30 MV/m with a ∼1 km size scale and a null field region of ∼0.5 km below that

Gamma‐ray glows associated with thunderclouds have been observed since the 1980s, however it remains unclear how, and at which thunderstorms gamma‐ray glows are generated in dense atmospheres. In this study, we report the first Compton camera imaging of a gamma‐ray glow from a winter thundercloud. On 14 January 2022, using two identical Bi4Ge3O12scintillators in energy range of 0.05–5 MeV, we detected two gamma‐ray glows lasting ∼4 min in a mountain area 25 km from the Japan Sea and 410 m above sea level. The same events were also observed by the Compton camera, where the first glow we observed suggested statistically significant (4.0 and 5.9 σlevel) signals of two enhanced concentrations in gamma‐ray photon images in a range of 0.15–1.5 MeV. These concentrations were most clearly observed in a time window of Δt= 50 s around the peak intensity of the gamma‐ray glow. Observations of gamma rays from thunderclouds started in 1980s, leading to intensive studies in the last 40 years. However, the question of where and how such gamma rays are produced in thunderclouds remains unclear, as no gamma‐ray images have been obtained to date. This paper presents the first successful gamma‐ray imaging of a thundercloud in a winter of Japan. In particular, we installed a Compton camera of 10 × 10 cm2in size, that is a compact but high sensitivity camera originally developed in the field of astronomy to observe gamma‐ray sky. At the peak of a gamma‐ray emission, we detected significant enhancements in the gamma‐ray photon image. The image provides the source position and beam pattern of the gamma‐ray emission, thus may be connected to highly electrified region and electron acceleration inside thunderclouds. Gamma‐ray glows were observed in a mountainous area 25 km from the Japan Sea and 410 m above sea level on 14 January 2022, during winterOne of the glows suggested two enhanced concentrations in gamma‐ray images, which was taken for the first time with a Compton cameraThe first successful gamma‐ray imaging provides a new means of investigating radiation beam pattern of gamma‐ray glows in thunderclouds Gamma‐ray glows were observed in a mountainous area 25 km from the Japan Sea and 410 m above sea level on 14 January 2022, during winter One of the glows suggested two enhanced concentrations in gamma‐ray images, which was taken for the first time with a Compton camera The first successful gamma‐ray imaging provides a new means of investigating radiation beam pattern of gamma‐ray glows in thunderclouds

Aim:The aim of this study was to determine the correlation between the growth hormone (GH)-insulin-like growth factor-I (IGF-I) axis and glucose intolerance in acromegaly during the early postoperative period. Subjects and Methods:The study included 20 patients with acromegaly caused by GH-secreting pituitary adenoma who received transsphenoidal surgery in our hospital. Glucose tolerance was evaluated with oral glucose tolerance tests (OGTTs) performed during pre- and early postoperative periods (9 [7–18] days after surgery). Homeostasis model assessment of insulin resistance (HOMA-IR) and insulinogenic index (IGI) were calculated, and correlation analyses were performed between these values and the GH-IGF-I axis. Patients were divided according to postoperative changes of the axis, and glucose tolerance was compared between the groups. Results:In preoperative OGTTs, nine patients had impaired glucose tolerance and two had diabetes mellitus patterns. Postoperatively, significant reduction was observed both in fasting plasma glucose levels (p<0.01) and in HOMA-IR (p<0.01), whereas IGI showed no significant change. HOMA-IR was significantly correlated with serum IGF-I levels both before (r=0.83, p<0.01) and after (r=0.57, p<0.01) surgery, although it was not correlated with serum GH levels. Patients who achieved more than 50% postoperative reduction in serum IGF-I levels showed significant improvement in OGTTs results (p<0.05). Conclusions:In patients with acromegaly, serum IGF-I levels, but not GH levels, were significantly correlated with insulin resistance. Early postoperative improvement of glucose tolerance is observed in patients who achieved postoperative reduction in serum IGF-I levels.

Winter thunderstorms in Japan have been recognized as an ideal target to observe high‐energy atmospheric phenomena thanks to low‐charge‐center cloud structures. During four winter seasons in Japan (from 2016 October to 2020 March), seven downward terrestrial gamma‐ray flashes (TGFs) were detected by gamma‐ray and broadband low‐frequency (LF: 0.8–500 kHz) monitors. All the detected TGFs took place at the initial stage of lightning flashes. Based on the LF observation, the seven downward TGFs in the present study can be classified into two types: energetic‐bipolar and small‐bipolar types. Three of them are energetic‐bipolar events, coincident with a high peak‐current LF pulse that originates from a negative return stroke with a peak current larger than 100 kA. The others are small‐bipolar events, followed by a negative bipolar LF pulse with a moderate peak current. Three of the four small‐bipolar events are multi‐pulse TGFs, while all of the energetic‐bipolar events in this study are single‐pulse TGFs. Terrestrial gamma‐ray flashes (TGFs) are a transient high‐energy emission from lightning discharges. While a lot of upward TGFs have been detected by satellites, a few downward TGF have been detected by ground‐based experiments. Our detection network in Japan has detected seven downward TGFs in winter thunderstorms for 4 years. Lightning discharges associated with the downward TGFs were also monitored in the low‐frequency radio band. The low‐frequency pulses associated with the downward TGFs can be classified into two types. Correlation analysis of downward TGFs with gamma‐ray and low‐frequency observations is a powerful approach to reveal the production mechanism of TGFs. Downward terrestrial gamma‐ray flashes (TGFs) in winter thunderstorms of Japan can be classified into two types based on low‐frequency (LF) observationsThree events were single‐pulse TGFs coincident with high peak‐current LF pulses of return strokesFour events were followed by moderate peak‐current LF pulses, and three of them are multi‐pulse TGFs Downward terrestrial gamma‐ray flashes (TGFs) in winter thunderstorms of Japan can be classified into two types based on low‐frequency (LF) observations Three events were single‐pulse TGFs coincident with high peak‐current LF pulses of return strokes Four events were followed by moderate peak‐current LF pulses, and three of them are multi‐pulse TGFs

Cosmic‐ray shower, hitting the atmosphere all the time, includes high‐energy electrons. Electric fields in thunderstorms accelerate these electrons so that they can reach farther distances with producing secondary electrons. The strong field above 0.284 MV m−1causes the Relativistic Runaway Electron Avalanches (RREA) process with an exponential increase of electrons. Even with lower electric fields below this RREA threshold which are usually measured in thunderstorms, an increase in electrons' kinetic energy and production of secondary electrons can occur without avalanche processes, known as Modification Of Spectra (MOS) of the cosmic‐ray shower. Both phenomena are related to observed gamma ray glow, which is bremsstrahlung emission from accelerated electrons in thunderstorms. We calculate an extended range and kinetic energy of electrons below the RREA threshold using an analytical evaluation and Geant4 Monte Carlo simulations. For example, at 0.280 MV m−1slightly below the RREA threshold, 3 MeV electrons gain 100% of their original kinetic energy through the passage of the continuous slowing down approximation (CSDA) range defined at the null electric field, which is consistent with results in previous studies as the transition to the RREA process. Even at a lower field of 0.260 MV m−1, the energy recovery by the field allows an injected 20 MeV electron beam to extend its average electron range from 73 m, in the null field configuration, to 562 m. We have performed analytical calculation and Geant4 simulations of atmospheric electron behavior for initial electron energy of 0.1–100 MeV and an electric field below 0.290 MV m−1. We develop calculations for e−spatial range with electric fields up to the avalanche threshold, 0.284 MV/m, related to gamma ray glowOur particle simulation shows that thunderstorm fields below avalanche level extend the range of 1–100 MeV electrons by a factor of 2–10The calculations indicate a transition to avalanche regime with 3 MeV electron under 0.280 MV/m that extends the spatial range to infinity We develop calculations for e−spatial range with electric fields up to the avalanche threshold, 0.284 MV/m, related to gamma ray glow Our particle simulation shows that thunderstorm fields below avalanche level extend the range of 1–100 MeV electrons by a factor of 2–10 The calculations indicate a transition to avalanche regime with 3 MeV electron under 0.280 MV/m that extends the spatial range to infinity

Background:Recently, it has been reported that the incidence of primary aldosteronism (PA) among patients with hypertension is much more frequent than previously reorted. Aim:In the present study, we investigated the frequency and features of PA associated with subclinical Cushing syndrome (SCS). Material and methods:Subjects included consecutive patients (no.=39) who were diagnosed as PA and performed adrenal venous sampling between 2003 and 2011 in our institute. Results:In 39 subjects who were diagnosed as PA, 29 patients were operated and 5 cases (12.8%) showed no suppression in low-dose dexamethasone suppression test. Four cases of them were demonstrated to be associated with SCS, and one was associated with overt Cushing syndrome (CS). Post-operatively, 3 cases received replacement therapy of hydrocortisone, while others did not. Pathological findings indicated the diagnosis of aldosterone-producing adenoma in 4 cases associated with SCS, and of idiopathic hyperaldosteronismin in one case associated with overt CS. In all 5 cases, immunohistochemical analysis demonstrated the immunoreactivities of both 3βHSD and P450c17 in the adrenocortical tumors, the marked cortical atrophy in the zona fasciculataand reticularis, the decreased dehydroepiandrosterone sulfotransferase expression, and suppression of hypothalamo-pituitary-adrenal axis indicating the autonomous secretion of cortisol from the tumor. Conclusions:The present study suggests that PA is frequently associated with SCS with prevalence of more than 10%, justifying the routine examinations for SCS in PA cases.

To minimise the volume of argon required for on-site tungsten inert gas welding of titanium plate, the authors investigated the behaviour of argon flow in a trailing–shielding box by means of computational fluid dynamics (CFD) simulations. In this study, a solid rectangular shielding box consisting of 9·5×105tetrahedral elements was modelled. Then, argon flow was simulated for two shielding parameters, namely, the argon supply rate and the gap between the box and the floor. In the experiment, the relation between the oxygen content in the shielding box and the shielding parameters was studied. The experimental results show that the simulation model used in the CFD simulations can predict the behaviour of argon. It is concluded that the simulation model is useful for improving the structure of the shielding box.

Alveolar macrophages (AMs) exposed to asbestos are well known to produce TNF-α, which induces the production of TGF-β1, leading to lung fibrogenesis. The present study examines the production of TGF-β1 by AMs exposed to chrysotile B asbestos (CH) in vivoor in vitroand the relationship between TGF-β1 production and apoptosis in cultures of AMs. Rats instilled with CH via the trachea showed increases in TNF-α, IL-1β and IL-6 in the bronchoalveolar lavage fluid (B ALF) 1 day after the instillation, followed by increases in TGF-β1 and apoptotic cells 5 days after. The AMs from these BALFs produced a significantly increased amount of TGF-β1 in culture compared to those from the control rats. The addition of 2.5 μg/cm2of CH augmented the production of TGF-β1 by the AMs from the control to the same level as produced by the AMs from the CH-treated rats. The apoptosis of AMs was not induced at 2.5 μg/cm2of CH, but was drastically induced at over 12.5 μg/cm2. In contrast, the production of TGF-β1 by AMs peaked at around 2.5 μg/cm2of CH, and it lasted for 11 days. In addition, Bcl-2 and Bcl-xLincreased in the AMs surviving under the exposure to CH. Taken together, these results indicate that AMs can autonomously, without other pulmonary cells, acquire the lasting ability to produce TGF-β1 independently of apoptosis under low exposure to CH. The AMs with the lasting production of TGF-β1 may contribute not only to lung fibrosis but also to immune suppression.

BACKGROUND AND STUDY AIMS: A newly designed magnifying endoscope featuring an endocytoscopy function provided by ultrahigh magnification was evaluated in a pilot study in patients with various types of benign and malignant pathology in the esophagus. PATIENTS AND METHODS: Seventy-five consecutive patients were included in the study from 15 March to 21 December 2005. Twenty-nine patients with specific esophageal lesions that had been detected by regular or narrow-band imaging, or both, were further evaluated using endocytoscopy, followed by tissue biopsy or resection. During the endocytoscopic examinations, the esophageal mucosa was stained with 0.5 % methylene blue. The endocytoscopic findings were graded from 1 to 5 in an endocytoscopic atypia (ECA) classification. The final histopathological diagnoses based on biopsies or resected specimens were as follows: category 1 in the Vienna classification, n = 4; category 2, n = 6; category 3, n = 1; category 4, n = 10; and category 5, n = 7. The endocytoscopic diagnoses were compared with the histopathological diagnoses. RESULTS: Clear endocytoscopic images were obtained in all cases. In definitely malignant lesions, the cell nuclei had an enlarged and irregularly arranged appearance (grade ECA 5). The positive predictive value for malignancy (grades ECA 4 and 5) was 94 %; the false-negative rate was 16.7 %, and the false-positive rate was 6.3 %. The overall accuracy of endocytoscopy for differentiating between nonmalignant tissue (categories 1 - 3 in the Vienna classification) and malignant tissue (categories 4 and 5) was 82 %. CONCLUSIONS: These preliminary results suggest that incorporating endocytoscopy facilities into a standard endoscope may be helpful in characterizing tissue in a variety of esophageal lesions. The potential clinical impact of this method in relation to other gastrointestinal organs requires further study.

BACKGROUND: Postoperative respiratory failure is often encountered in patients suffering from acute aortic dissection (AAD) and is believed to be influenced by release of neutrophil elastase after cardiopulmonary bypass. Sivelestat is a specific neutrophil elastase inhibitor, and this study aims to evaluate the effects of sivelestat on postoperative respiratory failure due to AAD. METHODS AND RESULTS: Patients who were operated for AAD from January 2000 to April 2005 and who had less than 300 mmHg initial postoperative PaO 2/FiO 2 were investigated retrospectively and divided into two groups. Group 1 (n = 9) received intravenous administration of sivelestat immediately after the operation, while Group II (n = 9) received no sivelestat. There were no significant differences between Group I and II with respect to patients' characteristics or background (age, body weight, operating time, cardiopulmonary bypass time, amount of bleeding, preoperative WBC number and initial PaO 2/FiO 2). Though patients in Group I showed a subtle improvement in certain parameters such as PaO 2/FiO 2, A-aDO 2 and respiratory index (RI) over a 3-day observation period compared to those of Group II, there were no significant differences. Neither postoperative mechanical ventilation time nor ICU stay differed between Group I and II. However, Group I showed a significantly greater improvement in the ratio of RI to initial RI on the 3POD compared to that of Group II (61.6 44.2 % vs. 111.9 40.9 %, P = 0.02). CONCLUSION: Inhibiting the activity of the neutrophil elastase may attenuate the postoperative respiratory complications of patients with AAD.

Abstract: Artificial hybridization studies have been carried out between plants with different photosynthetic types to study the genetic mechanism of photosynthetic types. However, there are only few reports describing the possibility of natural hybridization between plants with different photosynthetic types. A previous cytological and morphological study suggested that a cruciferous allotetraploid species, Diplotaxis muralis(L.) DC. (2n = 42), originated from natural hybridization between D. tenuifolia(L.) DC. (2n = 22) and D. viminea(L.) DC. (2n = 20). These putative parents have recently been reported to be a C3‐C4intermediate and a C3species, respectively. If this hybridization occurred, D. muralisshould have characteristics intermediate between those of the C3‐C4intermediate and C3types. We compared leaf structures and photosynthetic characteristics of the three species. The bundle sheath (BS) cells in D. tenuifoliaincluded many centripetally located chloroplasts and mitochondria, but those of D. vimineahad only a few organelles. The BS cells in D. muralisdisplayed intermediate features between the putative parents. Glycine decarboxylase P protein was confined to the BS mitochondria in D. tenuifolia,but accumulated mainly in the mesophyll mitochondria in D. viminea. In D. muralis,it accumulated in both the BS and the mesophyll mitochondria. Values of CO2compensation point and its response to changing light intensity were also intermediate between the putative parents. These data support the theory that D. muraliswas created by natural hybridization between species with different photosynthetic types.

To measure electron diffusion coefficients (D) and electron lifetimes (τ) of dye-sensitized solar cells (DSC), we introduced stepped light-induced transient measurements of photocurrent and voltage (SLIM-PCV), which can simplify the optical setup and reduce measurement time in comparison to conventional time-of-flight and frequency-modulated measurements. The method was applied to investigate the influence of the viscosity of a thermally stable high-boiling-point solvent on the energy conversion efficiency of DSCs. By systematic study of the influence of the viscosity, the species of cations as the counter charge of I^-/I3^-, and the concentrations of electrolytes, we concluded that a lower dye cation reduction rate due to slower iodine diffusion is a limiting factor for a highly viscous electrolyte system. On the other hand, comparable values of D and increased values of τ were observed in a highly viscous electrolyte. By employing 0.5 M TBAI and 0.05 M I2 in propylene carbonate, the efficiency of the DSC became comparable to that of a DSC using conventional electrolytes consisting of LiI, imidazolium iodide, and 4-tert-butylpyridine in methoxyacetonitrile. The simultaneous evaluation of D and τ through the appropriately simple measurement realizes fast optimization of the efficient and reliable DSC composed of thermally stable but often viscous electrolytes.

Current−voltage characteristics, electron lifetimes (τ), and electron diffusion coefficients (D) of dye-sensitized TiO2 solar cells (DSCs) composed of liquid electrolytes were repeatedly measured over a period of time. It was found that the energy conversion efficiency of the DSCs using electrolytes composed of Li⁺ or tetrabutylammonium cation as the counter charges of I^-/I3^- redox couples decreased with the lapse of time. On the other hand, such a decrease was not observed for the DSC consisting of 1,2-dimethyl-3-propylimidazolium cation or of Li⁺ coupled with the addition of tert-butylpyridine. The decrease of the efficiency was in accordance with a decreased electron lifetime. The notable decrease in the presence of Li⁺ is probably caused by the excess amount of Li⁺ adsorption on the TiO2 surface.

Abstract: Nano-structured TiO2 electrodes, suitable for dye sensitized solid-state solar cells were prepared by a new simple spraying technique (SPT). Physical properties of these electrodes were compared with the electrodes prepared by the ‘doctor blade’ technique (typical sliding method, DB). Dye sensitized solid-state solar cells, comprising of CuI as the hole conductor, were fabricated with these electrodes and enhanced photo responses were obtained with SPT electrodes. The effects of additives, either to the spray solution or to the hole conductor on the photoresponses of the above devices were also studied. The cells fabricated with SPT electrodes containing Al(BuiO)3 showed ∼ 2.4% efficiency and addition of 1-ethyl-3-methyl imidazolium thiocyanate into CuI layer further enhanced the efficiency up to 2.75% under the irradiance of 100 mW cm−2 (AM 1.5).

No Heading We have developed a new technique to study the transverse acoustic properties of superfluid 3He, employing a shear horizontal surface acoustic wave (SH-SAW) sensor. The transverse acoustic impedance can be obtained from the velocity and damping of SH-SAW which acoustically couples with liquid 3He all the interface. Since ultrasonic measurements provide the information about superfluid order-parameter through the excitation of collective modes, the SH-SAW sensor is expected to be a useful tool to study the boundary effect of superfluid 3He. Preliminary measurements were carried out at pressures of 17 and 23 bar, by the pulse transmission method at a frequency of 70 MHz. At 17 bar, imaginary squashing mode was observed as the sharp drop of the imaginary part of acoustic impedance. At 23 bar, the supercooled A-B phase transition was observed, as a jump of the real part of acoustic impedance, which was not observed in the warming process.

No Heading The transverse acoustic response in the B phase of superfluid 3He has been measured using an AC-cut quartz transducer at a pressure of 17.0 bar. The measurements were performed by a CW bridge method at a frequency of 9.3 MHz utilizing a quadrature hybrid and a high-frequency lock-in amplifier. By sweeping frequency around the resonance frequency of the transducer, in-phase and quadrature responses of the resonance were obtained from the output of the lock-in amplifier. We successfully separated the quality factor and the resonance frequency. Quality factor of the transducer had a small dip just below Tc and increased as ?n by cooling, while its resonance frequency decreased sharply at Tc and gradually recovered to the normal state value in the low temperature limit.

Many pseudotachylytes and their related fault rocks are found in the Hidaka metamorphic belt representing an ancient crustal section. On the basis of field observations of the pseudotachylytes and related fault rocks, nature of seismogenic faulting in the Hidaka crust is examined. The field observations suggest the following conclusions. (1) Two structural types of pseudotachylytes are distinguished: layer-parallel and layer-oblique. The latter are scattered in the metamorphic belt, but the former occur only in the southern part of the metamorphic belt. (2) An abundance of the layer-parallel pseudotachylytes suggests that earthquakes occurred repeatedly and frequently in the southern part, where complicated and duplicated crustal structures occur with many low-temperature thin mylonite zones. The southern part with such crustal structures was an ancient seismogenic area containing asperities and having a radius of a few tens of kilometers in the Hidaka crust. In the seismogenic area, the layer-parallel pseudotachylytes resulted from seismic slip on the mylonitic foliation within the low-temperature mylonite zones with strong preferred orientation of micas. (3) The layer-parallel pseudotachylytes and the subsequent layer-oblique pseudotachylytes post-date the latest and very-low-temperature mylonitization in the metamorphic belt. The former pseudotachylytes formed just above the upper side of the brittle-plastic transition zone.

The reactions of (phenylsulfinyl)furans or -thiophenes with carbon nucleophiles in the presence of trifluoroacetic anhydride allowed the nucleophilic installation of carbon functional groups on the furan and thiophene nuclei with complete regioselectivity.

Neonatal diarrhea occurred at two swine breeding farms in Hokkaido. Ten piglets aged 2 to 4 days were examined. Grossly, significant changes were confined to the small intestine. The mucous membrane was muddy and thickened. The intraluminal contents from the jejunum to the colon were liquid and yellow. In the small intestine, numerous Gram-negative bacilli preferentially adhered to the apex of villi. The mucosa was erosive with villous atrophy. There were bacilli also in the lamina propria and in the cytoplasm of degenerated enterocytes. Nonhemolytic Escherichia colistrains, belonging to serogroup E. coliO18 and possessing K88 fimbriae, were isolated from the small intestine. They could not be classified into any of the diarrheagenic E. coligroups because of the absence of genes of LT, STh, STp, VT1, VT2, eae, invE, and ipaH.After inoculation of the isolates on HEp-2 cells, some bacilli were engulfed by cytoplasmic projections resembling membrane ruffles and subsequently were localized in cytoplasmic vacuoles or free in the cytoplasm. These findings support the view that the present E. coliO18 is a new invasive strain enteropathogenic to piglets.

Transcripts that specifically accumulate in transgenic tobacco plants expressing an anti-sense construct for a tobacco type I DNA methyltransferase, NtMET1, were screened by the differential display method. Of the 31 genes identified, 16 encoded proteins with known functions; ten of these were related to biotic and abiotic stress responses, and the other six to cellular functions. In order to examine whether expression of these genes is correlated with DNA methylation status under natural stress conditions, a pathogen-responsive gene ( NtAlix1) was selected as representative, and assayed for transcript induction and genomic methylation in tobacco plants infected with tobacco mosaic virus (TMV). In inoculated leaves of wild-type plants, NtAlix1 transcripts began to accumulate 12 h after the onset of the hypersensitive response (HR), and levels remained high for up to 24 h. Changes in the methylation status at the locus became obvious 24 h later, as detected by digestion of genomic DNA with a methylation-sensitive restriction enzyme. The results suggest that the level of DNA methylation may change in response to external stresses, and that this is closely related to the activation of stress-responsive genes.

AbstractObjectives: We investigated the development of clinically overt nephritis in patients with silent lupus nephritis in an effort to determine predictors of onset. Methods: We selected 31 patients with systemic lupus erythematosus (SLE) who were diagnosed as having silent lupus nephritis between 1985 and 1995. Urinalysis, blood cell count, serum creatinine, complement levels, and anti-double-stranded DNA antibody (anti-dsDNA antibody) levels were followed retrospectively for at least 60 months in each patient. Results: During the follow-up period, 8 patients developed clinical renal disease and 23 had no renal impairment. The mean time of overt nephritis onset was 58 months and renal function deteriorated mildly in 3 patients. Although clinical and laboratory findings were not significantly different at SLE onset, patients with overt nephritis showed both persistent elevation of anti-dsDNA antibodies and persistently low levels of serum C3 and CH50 for at least 24 months before the onset of overt nephritis. Conclusions: Although the renal prognosis was relatively favorable, 25.8% of patients developed overt nephritis during the follow-up period. Elevation of anti-dsDNA antibodies with hypocomplementemia was persisted in these patients, suggesting the utility of these factors as predictors of clinical renal involvement in silent lupus nephritis.Copyright © 2004 S. Karger AG, Basel