Parametric attosecond pulse amplification far from the ionization threshold from high order harmonic generation in He.

Parametric amplification of attosecond coherent pulses around 100 eV at the single-atom level is demonstrated for the first time by using the 3D time-dependent Schrödinger equation in high-harmonic generation processes from excited states of He+. We present the attosecond dynamics of the amplification process far from the ionization threshold and resolve the physics behind it. The amplification of a particular central photon energy requires the seed XUV pulses to be perfectly synchronized in time with the driving laser field for stimulated recombination to the He+ ground state and is only produced in a few specific laser cycles in agreement with the experimental measurements. Our simulations show that the amplified photon energy region can be controlled by varying the peak intensity of the laser field. Our results pave the way to the realization of compact attosecond pulse intense XUV lasers with broad applications.

Nosocomial BK Polyomavirus Infection Causing Hemorrhagic Cystitis Among Patients With Hematological Malignancies After Hematopoietic Stem Cell Transplantation.

BK polyomavirus (BKPyV) is recognized as a pathogen that causes diseases such as hemorrhagic cystitis and nephritis after allogeneic hematopoietic stem cell transplantation (HSCT) or renal transplantation. BKPyV-associated disease is thought to occur through reactivation under immunosuppression. However, the possibility of its nosocomial transmission and the clinical significance of such transmission have not been elucidated. During a 6-month period, nine adult patients (median age: 47 years) who had hematological disorders and who were treated with HSCT (n = 7) or chemotherapy (n = 2) in a single hematology department developed hemorrhagic cystitis due to BKPyV infection. The polymerase chain reaction products of BKPyV DNA obtained from each patient were sequenced. Of the nine patients, six had subtype I, 2 had subtype IV, and 1 had subtype II or III. In the alignment of sequences, four and two of the six subtype I strains were completely homologous (100%). These results strongly suggest that BKPyV has the potential to cause nosocomial infection within a medical facility, especially among recipients of HSCT. Further studies are clearly warranted to elucidate the route(s) of BKPyV transmission in order to establish optimal infection control.

Spin injection into a superconductor with strong spin-orbit coupling.

We demonstrate spin injection into superconducting Nb by employing a spin absorption technique in lateral spin valve structures. Spin currents flowing in a nonmagnetic Cu channel are preferably absorbed into Nb due to its strong spin-orbit interaction, the amount of which dramatically changes below or above the superconducting critical temperature (TC). The charge imbalance effect observed in the Cu/Nb interface ensures that superconducting Nb absorbs pure spin currents even below TC. Our analyses based on the density of states calculated using the Usadel equation can well reproduce the experimental results, implying that the strong spin-orbit interaction of Nb is still effective for the spin absorption even below TC. Most importantly, our method allows us to determine the intrinsic spin relaxation time in the superconducting Nb, which reaches more than 4 times greater than that in the normal state.

Prevalence of delirium among outpatients with dementia.

BACKGROUND: Delirium and dementia are highly interrelated. However, few comprehensive epidemiological studies have examined this altered state of consciousness superimposed on dementia. We investigated the frequency of delirium in patients with dementia, its prevalence in patients with each dementia type, and its association with cerebrovascular disease (CVD) in patients with neurodegenerative dementias. METHODS: We studied 261 consecutive outpatients in the memory clinic of a psychiatric hospital between April 2010 and September 2011. All patients underwent routine laboratory tests and computed tomography (CT), and their Mini-Mental State Examination, Neuropsychiatric Inventory (NPI), Physical Self-Maintenance Scale (PSMS), and Delirium Rating Scale - Revised 98 scores were recorded. The diagnosis of delirium was based on the Diagnostic and Statistical Manual of Mental Disorders, fourth edition, text revision. CVD was detected by CT. RESULTS: Among the 206 patients with dementia, delirium was present in 40 (19.4%). The proportion of patients who experienced episodes of delirium was 14.7% in the Alzheimer's disease, 34.4% in the vascular dementia, 31.8% in the dementia with Lewy bodies, and none in frontotemporal lobar degeneration. Delirium was frequently observed in patients with dementia and CVD. The NPI total and agitation subscale scores were significantly higher in dementia patients with delirium than in those without delirium. PSMS scores were significantly lower for patients with delirium than for patients without delirium. CONCLUSIONS: The frequency of delirium varies with each dementia type. In addition, delirium decreases activities of daily living, exaggerates behavioral and psychological symptoms dementia, and is associated with CVD in patients with neurodegenerative dementias.

Prognostic significance of hypoxia-inducible factor-1α expression in advanced pharyngeal cancer without human papillomavirus infection.

OBJECTIVE: This study aimed to clarify the association between both hypoxia-inducible factor-1α and glucose transporter type-1 expression and survival outcome in advanced pharyngeal cancer without human papillomavirus infection. METHOD: Twenty-five oropharyngeal and 55 hypopharyngeal cancer patients without human papillomavirus infection were enrolled. All patients had stage III-IV lesions and underwent concurrent chemoradiotherapy or surgery. Hypoxia-inducible factor-1α and glucose transporter type-1 expression were investigated in primary lesions by immunohistochemistry. RESULTS: There were 41 and 39 cases with low and high hypoxia-inducible factor-1α expression, and 28 and 52 cases with low and high glucose transporter type-1 expression, respectively. There was no significant correlation between hypoxia-inducible factor-1α and glucose transporter type-1 expression. In univariate analysis, nodal metastasis, clinical stage and high hypoxia-inducible factor-1α expression, but not glucose transporter type-1 expression, predicted significantly worse prognosis. In multivariate analysis, hypoxia-inducible factor-1α overexpression was significantly correlated with poor overall survival, disease-specific survival and recurrence-free survival. CONCLUSION: High hypoxia-inducible factor-1α expression was an independent risk factor for poor prognosis for advanced human papillomavirus-unrelated pharyngeal cancer.

Metallic ground states of undoped Ti2O3 films induced by elongated c-axis lattice constant.

Ti2O3 exhibits unique metal-insulator transition (MIT) at ~ 450 K over a wide temperature range of ~ 150 K. The close relationship between MIT and crystal deformation has been proposed. However, as physical properties are governed by the thermodynamic equilibrium in bulk systems, conducting experimental studies under different lattice deformations remains challenging. Epitaxial thin films can offer high flexibility to accommodate adaptive crystal lattices and provide efficient platforms for investigating the MIT. In this study, we report the synthesis of corundum-type Ti2O3 films on various growth temperatures. We found that the metallic ground states appeared in the films grown at low temperatures. The electronic ground states were further investigated by the electronic-structure calculations. Results suggest that the electrical properties of Ti2O3 films were governed by the c/a ratio of the crystal structure, and the absence of the MIT was attributed to the lattice deformation characterized by an elongated c lattice constant.

Nosocomial infection by human bocavirus and human rhinovirus among paediatric patients with respiratory risks.

BACKGROUND: Nosocomial infections by respiratory viruses undetected by rapid tests are not often diagnosed. For paediatric patients with background diseases, nosocomial infection could be fatal. AIM: To determine the relationship between developing symptoms by respiratory viruses undetectable by rapid tests and respiratory risks and to improve the management of infection control. METHODS: Two episodes of nosocomial infection by human bocavirus (HBoV) and human rhinovirus (HRV) were retrospectively investigated in a tertiary hospital paediatric ward in Japan. Viruses were identified by polymerase chain reaction to determine infection control management. When viruses of the same species were detected from different patients, the virus homology was investigated. The relationship between respiratory risks and developing symptoms was statistically investigated. FINDINGS: Three and four patients with respiratory risks in the HBoV and HRV outbreaks, respectively, developed respiratory symptoms. The nucleotide sequences of two patients in the HBoV outbreak and all four patients in the HRV outbreak were phylogenetically close. In both outbreaks, the patients with respiratory risks developed significantly more symptoms than those without any risk (P = 0.035 and 0.018, respectively). After the patients with respiratory infection were separated from those with respiratory risks, no additional nosocomial infection occurred. CONCLUSION: Patients with respiratory risks easily develop respiratory symptoms and acquire severe symptoms of nosocomial infection by those viruses. In a paediatric ward, we should adopt not only standard precautions but also isolation management of the patients with respiratory symptoms, even if they have negative results in rapid tests.

First report of hepatobiliary Mycobacterium avium infection developing obstructive jaundice in a patient with neutralizing anti-interferon-gamma autoantibodies.

This study describes a patient who experienced hepatobiliary Mycobacterium avium infection associated with neutralizing anti-interferon gamma (IFN-γ) autoantibodies during treatment for disseminated M. avium disease. Hepatobiliary M. avium infection should be considered in jaundiced patients with neutralizing anti-IFN-γ autoantibodies, including those receiving antimycobacterial therapy for disseminated M. avium disease.

Accuracy of an interferon-gamma release assay to detect active pulmonary and extra-pulmonary tuberculosis.

OBJECTIVE: To examine the performance of an interferon-gamma (IFN-gamma) release assay (QuantiFERON-TB 2G assay [QFT-G]) to detect Mycobacterium tuberculosis infection in a Japanese general hospital, for the diagnosis of active pulmonary tuberculosis (PTB) and extra-pulmonary tuberculosis (EPTB). DESIGN: We prospectively examined the performance of QFT-G in 194 patients suspected of active TB. Diagnosis was confirmed by 1) positive M. tuberculosis cultures, or 2) clinical manifestations or laboratory or pathological findings consistent with active TB and response to specific therapy. RESULTS: Three patients with indeterminate QFT-G results were excluded. Among the remaining 191 patients, 77 had active TB. When the cut-off concentration of IFN-gamma was set at 0.35 IU/ml, as recommended by the manufacturer, the assay was positive in 69 patients and negative in 122. The sensitivity of the assay was 76.6% in all patients, 74.5% in the 47 patients with PTB and 80.0% in the 30 patients with EPTB. The overall specificity of the assay was 91.2%. CONCLUSION: Although the specificity of the QFT-G to detect active TB was high and its sensitivity low, it was as accurate for the detection of active EPTB as for PTB when the 0.35 IU/ml INF-gamma cut-off concentration was used.

Health-related QOL of elderly patients with pulmonary M. avium complex disease in a university hospital.

BACKGROUND: Little is known about the clinical characteristics and health-related quality of life (HQOL) of elderly patients with pulmonary Mycobacterium avium complex (pMAC) disease. OBJECTIVES: To evaluate HQOL using the 36-Item Short-Form Health Survey and St George's Respiratory Questionnaire (SGRQ) and to investigate the predictors of HQOL changes among elderly patients with pMAC disease. METHODS: This prospective cohort registry was conducted at Keio University Hospital, Tokyo, Japan, between May 2012 and July 2015 and included 84 patients with pMAC disease aged 75 years who had completed the HQOL questionnaire and 48 patients with pMAC disease who had been followed up and completed the HQOL questionnaire in cross-sectional and longitudinal analyses, respectively. RESULTS: In cross-sectional analyses, elderly patients with pMAC disease had significantly lower role-physical, general health, vitality, social functioning, role-emotional and role/social component scores than the general Japanese elderly population. Analysis of covariance revealed that patients with cavitary lesions had significantly worse physical functioning and SGRQ scores (P < 0.05). Longitudinal analysis showed that under-treatment, short duration of disease and positive sputum smear at baseline were predictors of worse HQOL at 12 months. CONCLUSIONS: Elderly patients with pMAC disease have reduced HQOL. Further large studies on HQOL are required to refine the use of this parameter in the treatment of these patients.

Enhancement of double auger decay probability in xenon clusters irradiated with a soft-x-ray laser pulse.

The interaction of large Xe clusters with a soft x-ray laser pulse having a wavelength of 13.9 nm and an intensity of up to 2x10(10) W/cm2 was investigated using a time-of-flight ion mass spectrometer. The corresponding laser photon energy was sufficiently high to photoionize Xe 4d innershell electrons. It was found that Xe3+ ions (which result from double Auger decay of 4d vacancies) became the dominant final ionic product with increasing cluster size and x-ray intensity. This is in contrast to the results of synchrotron radiation experiments involving free Xe atoms, in which Xe2+ is the dominant resultant ion species. Possible mechanisms responsible for the enhancement of the double Auger transition probability in x-ray laser and cluster interaction are discussed.

Impact of combinatorial dysfunctions of Tet2 and Ezh2 on the epigenome in the pathogenesis of myelodysplastic syndrome.

Somatic inactivating mutations in epigenetic regulators are frequently found in combination in myelodysplastic syndrome (MDS). However, the mechanisms by which combinatory mutations in epigenetic regulators promote the development of MDS remain unknown. Here we performed epigenomic profiling of hematopoietic progenitors in MDS mice hypomorphic for Tet2 following the loss of the polycomb-group gene Ezh2 (Tet2KD/KDEzh2Δ/Δ). Aberrant DNA methylation propagated in a sequential manner from a Tet2-insufficient state to advanced MDS with deletion of Ezh2. Hyper-differentially methylated regions (hyper-DMRs) in Tet2KD/KDEzh2Δ/Δ MDS hematopoietic stem/progenitor cells were largely distinct from those in each single mutant and correlated with transcriptional repression. Although Tet2 hypomorph was responsible for enhancer hypermethylation, the loss of Ezh2 induced hyper-DMRs that were enriched for CpG islands of polycomb targets. Notably, Ezh2 targets largely lost the H3K27me3 mark while acquiring a significantly higher level of DNA methylation than Ezh1 targets that retained the mark. These findings indicate that Ezh2 targets are the major targets of the epigenetic switch in MDS with Ezh2 insufficiency. Our results provide a detailed trail for the epigenetic drift in a well-defined MDS model and demonstrate that the combined dysfunction of epigenetic regulators cooperatively remodels the epigenome in the pathogenesis of MDS.

Burst intensification by singularity emitting radiation in multi-stream flows.

Burst Intensification by Singularity Emitting Radiation (BISER) is proposed. Singularities in multi-stream flows of emitting media cause constructive interference of emitted travelling waves, forming extremely localized sources of bright coherent emission. Here we for the first time demonstrate this extreme localization of BISER by direct observation of nano-scale coherent x-ray sources in a laser plasma. The energy emitted into the spectral range from 60 to 100 eV is up to ~100 nJ, corresponding to ~1010 photons. Simulations reveal that these sources emit trains of attosecond x-ray pulses. Our findings establish a new class of bright laboratory sources of electromagnetic radiation. Furthermore, being applicable to travelling waves of any nature (e.g. electromagnetic, gravitational or acoustic), BISER provides a novel framework for creating new emitters and for interpreting observations in many fields of science.

Effects of habitual aerobic exercise on the relationship between intramyocellular or extramyocellular lipid content and arterial stiffness.

The accumulation of intramyocellular lipid (IMCL) and extramyocellular lipid (EMCL) is associated with arterial stiffness in middle-aged and older adults. Habitual aerobic exercise induces the improvement of arterial stiffness with reduction in fat accumulation. However, the relationship between aerobic exercise-induced changes in muscular lipids and arterial stiffness remains unclear. The purpose of this study was to investigate whether habitual aerobic exercise-induced changes in IMCL and EMCL content would lead to an improvement of arterial stiffness. First, in a cross-sectional study, we investigated whether cardiorespiratory fitness level affects the association between IMCL or EMCL content and arterial stiffness in 60 middle-aged and older subjects (61.0±1.3 years). Second, in an intervention study, we examined whether aerobic exercise training-induced changes in IMCL and EMCL content are associated with a reduction in arterial stiffness in 18 middle-aged and older subjects (67.0±1.7 years). In the cross-sectional study, IMCL content was negatively correlated with brachial-ankle pulse wave velocity (baPWV) (r=-0.47, P<0.05), whereas EMCL content was positively correlated with baPWV (r=0.48, P<0.05) in the low-fitness group, but was not correlated in the high-fitness group. Furthermore, 8-week aerobic exercise training in older adults increased IMCL content and reduced EMCL content. The training-induced change in baPWV was negatively correlated with training-induced changes in IMCL but was positively correlated with training-induced changes in EMCL. These findings suggest that aerobic exercise training-induced changes in IMCL and EMCL content may be related to a reduction in arterial stiffness in middle-aged and older adults.

Elevated pentraxin 3 level at the early stage of exercise training is associated with reduction of arterial stiffness in middle-aged and older adults.

Regular exercise improves aging-induced deterioration of arterial stiffness, and is associated with elevated production of pentraxin 3 (PTX3) and anti-inflammatory as well as anti-atherosclerotic effects. However, the time-dependent effect of exercise training on arterial stiffness and PTX3 production remains unclear. The purpose of this study was to investigate the time course of the association between the effects of training on the circulating PTX3 level and arterial stiffness in middle-aged and older adults. Thirty-two healthy Japanese subjects (66.2±1.3 year) were randomly divided into two groups: training (exercise intervention) and sedentary controls. Subjects in the training group completed 8 weeks of aerobic exercise training (60-70% peak oxygen uptake (VO2peak) for 45 min, 3 days per week); during the training period, we evaluated plasma PTX3 concentration and carotid-femoral pulse wave velocity (cfPWV) every 2 wk. cfPWV gradually declined over the 8-week training period, and was significantly reduced after 6 and 8 week of exercise intervention (P<0.05). Plasma PTX3 level was significantly increased after 4 weeks of the intervention (P<0.05). In addition, the exercise training-induced reduction in cfPWV was negatively correlated with the percent change in plasma PTX3 level after 6 week (r=-0.54, P<0.05) and 8 weeks (r=-0.51, P<0.05) of the intervention, but not correlated at 4 weeks. Plasma PTX3 level was elevated at the early stage of the exercise training intervention, and was subsequently associated with training-induced alteration of arterial stiffness in middle-aged and older adults.

Nonlinear increase of X-ray intensities from thin foils irradiated with a 200 TW femtosecond laser.

We report, for the first time, that the energy of femtosecond optical laser pulses, E, with relativistic intensities I > 10(21) W/cm(2) is efficiently converted to X-ray radiation, which is emitted by "hot" electron component in collision-less processes and heats the solid density plasma periphery. As shown by direct high-resolution spectroscopic measurements X-ray radiation from plasma periphery exhibits unusual non-linear growth ~E(4-5) of its power. The non-linear power growth occurs far earlier than the known regime when the radiation reaction dominates particle motion (RDR). Nevertheless, the radiation is shown to dominate the kinetics of the plasma periphery, changing in this regime (now labeled RDKR) the physical picture of the laser plasma interaction. Although in the experiments reported here we demonstrated by observation of KK hollow ions that X-ray intensities in the keV range exceeds ~10(17) W/cm(2), there is no theoretical limit of the radiation power. Therefore, such powerful X-ray sources can produce and probe exotic material states with high densities and multiple inner-shell electron excitations even for higher Z elements. Femtosecond laser-produced plasmas may thus provide unique ultra-bright X-ray sources, for future studies of matter in extreme conditions, material science studies, and radiography of biological systems.

Epidermal growth factor suppresses in vitro senescence in the ability of human umbilical vein endothelial cells to proliferate, but not in the ability to produce prostacyclin.

Addition of epidermal growth factor (EGF) to culture medium extended the replicative life span of human umbilical vein endothelial (HUVE) cells in culture. In brief, EGF suppresses the age-related decrease (in vitro senescence) in cell proliferative ability. However, the addition of EGF did not extend the culture period in which prostacyclin (PGI2) is actively produced by the cells. Therefore, EGF does not suppress the age-related decrease (in vitro senescence) in the ability of cultured HUVE cells to produce PGI2. These results suggest that the process of in vitro senescence in the cell proliferative ability is not necessarily correlated with that of in vitro senescence in the ability to produce PGI2.

No relationship between the age-related decrease in prostacyclin production and the level of intracellular lipid peroxidation in human umbilical vein endothelial cells in culture.

Some investigators have speculated that a decrease in prostacyclin production observed during ageing of endothelial cells is caused by an increase in intracellular lipid peroxide. We checked this speculation using an in vitro model to study the ageing of human vascular endothelial cells. For this purpose we determined the levels of intracellular lipid peroxide of endothelial cells at various culture ages, and found that the level of intracellular lipid peroxidation did not increase during in vitro ageing. Amounts of intracellular lipid peroxide also differed depending on the growth phase, the addition of heparin and the strain of endothelial cells, but the cells producing prostacyclin at a low level did not necessarily contain larger amounts of intracellular lipid peroxide. Therefore, we postulate that the age-related decrease in prostacyclin production is not due to an increase in the amount of intracellular lipid peroxide as a function of age.

A step in the process of prostacyclin production whose decline leads to the age-related decrease in production by human umbilical vein endothelial cells in culture.

Human umbilical vein endothelial (HUVE) cells were examined at various culture ages for four steps of prostacyclin (PGI2) production ((1) incorporation of exogenous arachidonic acid into the cell membrane, (2) loss of arachidonic acid from the cell membrane to the cytoplasm, (3) conversion of arachidonic acid to PGI2 in the cytoplasm, (4) release of PGI2 to the outside of the cell) to determine the step whose decline leads to the age-related decrease in PGI2 production. Only conversion to PGI2 (step 3) showed the age-related decrease. Judging from these results, the authors conclude that the age-related decrease in PGI2 production is mainly due to the decrease in the ability of HUVE cells to convert arachidonic acid to PGI2 in the cytoplasm.