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Second harmonic generation (SHG) spectroscopy in the visible and infrared regions has been a useful tool to selectively probe electronic properties at surfaces and interfaces. By examining variation of SHG under a magnetic field, one can also evaluate magnetic properties at the surfaces/interfaces. When multiple elements are involved in SHG, however, it is difficult to separate their contributions. In order to meet the demand of studying increasingly complex magnetic multilayer materials, element selectivity is desired. Here, using an Fe-based multilayer sample with broken inversion symmetry, we present observation of magnetization-induced SHG in the soft x-ray regime around the Fe M-shell absorption edge. Significant variation of SHG signal was captured depending on the direction of the magnetic moment, assuring sensitivity of the measurement likely enhanced by the Fe M-edge inner-shell resonance. The present methodology paves the way for element specific studies of magnetic properties at buried interfaces.

Objectives The aim of this AFIRE (Atrial Fibrillation and Ischemic Events With Rivaroxaban in Patients With Stable Coronary Artery Disease) trial subgroup analysis was to examine rivaroxaban monotherapy benefits and their relation to the time between stenting and enrollment among patients after coronary stenting. Background Of 2,215 patients with atrial fibrillation and stable coronary artery disease in the AFIRE trial, rivaroxaban monotherapy was noninferior to rivaroxaban plus antiplatelet therapy (combination therapy) in terms of efficacy and superior for safety endpoints. However, thrombotic risk after antiplatelet therapy cessation remained a concern among 1,444 patients who had undergone coronary stenting >1 year before enrollment. Methods The benefits of rivaroxaban monotherapy in coronary stenting subgroups were assessed for efficacy (a composite of stroke, systemic embolism, myocardial infarction, unstable angina requiring revascularization, or death of any cause), safety (major bleeding defined according to International Society on Thrombosis and Haemostasis criteria), ischemic endpoints, net adverse clinical event, and time between stenting and enrollment. Results Efficacy and safety endpoints for monotherapy were superior to combination therapy, with HRs of 0.70 for efficacy (95% CI: 0.50-0.98; P = 0.036) and 0.55 for safety (95% CI: 0.33-0.92; P = 0.019). For ischemic endpoints, the HR was 0.82 (95% CI: 0.58-1.15; P = 0.240). The HR became smaller with longer time between stenting and enrollment (efficacy, P for interaction = 0.158; safety, P = 0.097). Conclusions In patients with atrial fibrillation after coronary stenting, the benefits of rivaroxaban monotherapy for efficacy and safety endpoints were consistent with those in the whole AFIRE trial population. The benefits became apparent with longer time between stenting and enrollment. (Atrial Fibrillation and Ischemic Events With Rivaroxaban in Patients With Stable Coronary Artery Disease Study [AFIRE]; UMIN000016612 , NCT02642419 )

Funding Acknowledgements Type of funding sources: None. Background In patients with sludge or severe spontaneous echo contrast (SEC) in the left atrial appendage (LAA), isoproterenol loading transesophageal echocardiography (ISP-TEE) has been reported to check the presence of thrombus in the LAA, as the sludge or severe SEC disappears (Figure 1). Purpose The aim of this study was to assess the safety of ISP-TEE for the identification of LAA thrombus and the hemodynamic changes in the LAA caused by ISP loading. Methods We prospectively enrolled 25 patients with atrial fibrillation (AF) and sludge or SEC in the LAA who underwent ISP-TEE from April 2020 to July 2021. ISP was administered intravenously to achieve the target heart rate (HR) defined as follows: Max HR [beats per minutes: bpm] = 220 – age (years), Target HR [bpm] = Max HR × 0.8. Patients with tachycardia exceeding Max HR before ISP administration, hemodynamic instability, and other contraindications to ISP were excluded from the study. To assess the safety of ISP-TEE, we evaluated patients’ condition, changes in systolic blood pressure (sBP) and HR before and after ISP loading. We also assessed the presence or absence of worsening heart failure, new arrhythmias other than atrial fibrillation, and cerebral infarction or transient ischemic attack during the examination, and after 24 hours. Hemodynamic evaluation was performed using LAA blood flow velocity, LAA tissue Doppler imaging (TDI) velocity, and LAA volume fraction (LAAVF) defined as follows: LAAVF (%) = (Max LAA volume – Min LAA volume) / Max LAA volume × 100. Quantification of LAA volume was performed using the stacked-contour method of a 3-dimensional TEE full-volume acquisition. Results Among 25 patients, 13 patients had sludge or grade3 SEC, 7 patients had grade2 SEC, 5 patients had grade1 SEC. HR after ISP loading was significantly higher than before loading, but sBP did not change significantly before and after ISP loading. No complications due to ISP loading were observed during examination and after 24 hours. After ISP loading, there were 18 patients with grade 1 SEC or no SEC (classified as Group1), 7 patients had residual sludge or grade 2 to 3 SEC (classified as Group2). The differences in LAA blood flow velocity between before and after ISP loading was faster in Group1 than in Group2: 13.0 ± 10.5 vs 2.6 ± 4.2. p = 0.019. The differences in TDI velocity was also faster in Group1 than in Group2: 1.46 ± 1.14 vs 0.19 ± 0.50, p = 0.010. The differences in LAAVF was higher in Group1 than in Group2: 13.7 ± 10.3 vs 2.2 ± 2.0, p = 0.009. Conclusions In our study, no complications were observed in ISP-TEE for the identification of LAA thrombus. Patients with grade 1 SEC or no SEC, the LAA function was increased by ISP loading. These results may provide insights into the mechanisms of ISP loading on SEC in the LAA. Abstract Figure.

Background Early detection of pulmonary hypertension (PH) is crucial to ensure that patients receive timely treatment for the progressive clinical course. The chest X-ray (CXR), a routine method at hospitals, has recommended in order to reveal features supportive of a diagnosis of PH. However, it is well known that the sensitivity and specificity are low. Purpose We tested the hypothesis that application of artificial intelligence (AI) to the CXR could identify PH. Methods We retrospectively enrolled 900 data with paired CXR and right heart catheter (RHC), including the pulmonary artery pressure, from October 2009 to December 2018. We trained a convolutional neural network to identify patients with PH as actual value of pulmonary artery pressure, using the CXR alone (Figure). The diagnosis of PH was performed using hemodynamic measurements according to the most recent World Symposium standards: mean PAP ≥20 mmHg. We have compared the area under the curve (AUC) by human observers, measurements of CXR images, and AI for detection of PH. Results Subjects were divided into two groups with PH (439 patients; mean age, 66±14 years; 233 male) and without PH (461 patients; mean age, 68±12 years; 278 male). In an independent set, AI was the highest diagnostic ability for detection of PH (AUC: 0.71). The AUC by the AI algorithm was significantly higher than the AUC by measurements of CXR images and human observers (0.71 vs. 0.60 and vs. 0.63, all compared p Conclusion Applying AI to the CXR (a classical, universal, low-cost test) permits the CXR images to serve as a powerful tool to screen for PH. Neural network Funding Acknowledgement Type of funding source: None

Intraparticle charge delocalization occurs when metal nanoparticles are functionalized with organic capping ligands through conjugated metal-ligand interfacial bonds. In this study, metal nanoparticles of 5d metals (Ir, Pt, and Au) and 4d metals (Ru, Rh, and Pd) were prepared and capped with ethynylphenylacetylene and the impacts of the number of metal d electrons on the nanoparticle optoelectronic properties were examined. Both FTIR and photoluminescence measurements indicate that intraparticle charge delocalization was enhanced with the increase of the number of d electrons in the same period with palladium being an exception.

Background: As was reported, gefitinib (Iressa®) showed a strong growth inhibitory effect on non-small-cell lung cancer PC-9 cells with mutant EGFR, but did not so much on A549 cells with wild-type EGFR. Observation: We here demonstrated by isobolograms and combination index analyses that the paired combinations of gefitinib with flavonoids from Wogon (Scutellaria baicalensis root): wogonin, oroxylin A and chrysin exerted synergistic anti-tumor effects against A549 cells. Result: The cell cycle analyses revealed that the combination of gefitinib and oroxylin A in A549 cells induced more apoptotic cells than other paired combinations as well as gefitinib alone. Thus, it is anticipated that oroxylin A could help to enhance the remission rate in the gefitinib therapy for the patients with non-small cell cancer cells with wild-type EGFR which provide a poor prognosis. Conclusion: Since the Wogon flavonoids, wogonin, oroxylin A and chrysin, accelerated the acetylation of Lysine residues of histone proteins, it is suggested that they put forth anti-tumor activities through inhibition of histone deacetylases which mediated the post-translational modification of histones.

Background Lambl’s excrescences (LEs), filiform strands that occur at sites of cardiac valves, have been suggested the cause cryptogenic stroke. The diagnosis is primarily based upon the echocardiographic study, but conventional two-dimensional transthoracic echocardiography has limitation to detect such as small strands. Latest three dimensional-transesophageal echocardiography (3D-TEE) have high-resolution images with many slices, so small structures are able to be clearly visible and detected. Purpose The aim of this study was to assess the prevalence of LEs using the latest 3D-TEE images. Methods We retrospectively reviewed consecutive 140 patients who underwent 3D-TEE from November 2018 to May 2019. Forty-seven patients were excluded due to unmeasurable, such as mitral valve prolapse, severe aortic stenosis, prosthetic valves and poor-quality images. We carefully evaluated the mitral and aortic valve leaflets in order to find mobile string structure (diameter Results Among 93 patients, 83 patients (89%) was detected the presence of LEs. No difference in age and gender were found between patients with LEs and patients without LEs. Of the total 83 patients, there were 35 patients with strands on mitral valve, 32 patients with strands on aortic valve, and 16 patients with strands on both valves. Distribution of LEs at each valve leaflet were shown in Figure. Right coronary cusp of aortic valve (42%) and P2 of mitral valve (35%) were high prevalence among leaflets. Conclusions 3D-TEE provides an update prevalence of LEs. The prevalence of LEs might be potentially high in the real world. Abstract P1526 Figure.

Background Precise and reliable echocardiographic assessment of LVEF is needed for clinical decision-making. LVEF is currently determined through an observer dependent process that requires manual tracing. To remove this manual tracing step, which is both time-consuming and user dependent, automatic computer aided diagnosis systems may be useful in the clinical setting. Purpose The aim of this study was to evaluate whether a 3-dimensional convolutional neural networks (3DCNN) could estimate left ventricular ejection fraction (LVEF) and differentiate types of heart failure (preserved EF/reduced EF) using conventional 2-dimensional echocardiographic images. Methods We developed a deep learning model to automatically estimate LVEF from echocardiographic data. The 3DCNN model was trained on a dataset of 340 patients. The dataset creation consisted of three main steps: firstly, for each exam, cine-loops showing the parasternal and apical views were manually selected; then, 10 sequential frames were extracted from each 1 beat and; finally, each frame was pre-processed to fit the learning model. Each patient has 2 views, resulting in a total of 6,800 images. Reference LVEF measurement was calculated by two highly experienced readers in each case. Results A good correlation was found between estimated LVEF based on apical 2 and 4 chamber views and reference LVEF (r =0.88, p Conclusions The 3DCNN can be applied to estimate and classify the LVEF in the clinical setting. Furthermore, this work will serve as a driver for future research using million image databases. Abstract 540 Figure.

Background Epicardial adipose tissue (EAT) locates anatomically and functionally contiguous to the myocardium and coronary arteries. It has been suggested that EAT accumulation is associated with cardiac remodeling and impaired cardiac performance. However, its role in left ventricular (LV) wall strain remains unclear. Purpose In this study, we aimed to clarify: whether EAT accumulation is related to global longitudinal (GLS), circumferential (CS) and radial strain (RS); and if so, in which extent or by which amount of EAT are required to deteriorate these strain. Methods Total 180 patients who had no obstructive coronary artery disease (CAD) on multi-detector computed tomography (MDCT) coronary angiography and normal left ventricular ejection fraction (LVEF) on conventional echocardiography were recruited. Cardiac CT was used to quantify EAT volume (EATV) and echocardiographic speckle tracking was used to measure the GLS, CS and RS. EATV index (EATV/Body surface area) was determined as: EAT volume, the sum of the EAT area from the base to the apex of the heart (cm3)/body surface area (m2). Adipose tissue was determined as the density range between −190 and −30 Hounsfield unit. According to the median value (68 cm3/m2), patients were divided into lower and higher EATV index two groups. Results In higher EATV index group (95±19 cm3/m2), mean age, body mass index (BMI), prevalence of hyperlipidemia and prevalence of CAD were larger than in lower EATV index group (48±14 cm3/m2). Male gender, hypertension, diabetes, smoking and LV mass index were comparable between two groups. Patients in higher EATV index had lower GLS than those in lower EATV index (−19.4±1.2% vs. −18.8±1.3%, p=0.002). However, there were no significant difference between two groups regarding to the CS and RS. Linear regression analysis showed that there was strong correlation between EATV index and GLS (R=0.216, p=0.004); whereas, both RS and CS were strongly associated with the interventricular septum thickness (RS: R=0.248, p=0.003; CS: R= −0.192, p=0.023) and relative wall thickness (RS: R=0.178, p=0.036; CS: R= −0.184, p=0.030) but not with EATV; on multiple regression analysis, EATV was a predictor of GLS independent of age, male gender, BMI, diabetes, hyperlipidemia, hypertension and CAD (Adjusted R2=0.238, p Conclusion EATV is independently associated with GLS despite the preserved LVEF and lacking of obstructive CAD, and may play a significant role in estimating impaired longitudinal LV performance.

Ethynylferrocene-functionalized titanium dioxide nanoparticles (TiO 2 -eFc) were synthesized, for the first time ever, by a modified two-phase hydrothermal method. Transmission electron microscopic measurements showed that the nanoparticles were rather uniform in size, with an average diameter of 4.0 ± 0.5 nm and well-defined lattice fringes that were consistent with those of anatase TiO 2 . 1 H NMR, FTIR and XPS measurements confirmed the attachment of the ferrocenyl ligands onto the nanoparticle surface, most likely forming Ti−C C−Fc interfacial bonds. The resulting nanoparticles exhibited a bandgap of ca. 3.3 eV, and two emission bands in photoluminescence measurements at 351 and 460 nm, with the former due to the TiO 2 cores whereas the latter from intraparticle charge delocalization between the nanoparticle-bound acetylene moieties under UV photoirradiation. In electrochemical measurements, only one pair of voltammetric peaks were observed in the dark, due to the redox reactions of the nanoparticle-bound ferrocenyl groups. However, when subject to photoirradiation with UV lights (254 and 365 nm), two pairs of voltammetric peaks appeared, with a respective peak spacing of 174 and 198 mV, suggesting intervalence charge transfer (IVCT) between the ferrocenyl moieties bound on the nanoparticle surface. This arose from photo-enhanced electrical conductivity of the TiO 2 cores that served as part of the chemical linkage bridging the ferrocenyl moieties. Significantly, such photo-gated IVCT varied with the photoexcitation energy that dictated the intraparticle charge transfer pathways.

Pulmonary lymphoepithelioma-like carcinoma is a rare type of non–small cell lung cancer. The tumor is usually discovered in young, nonsmoking Asian populations. The patients are diagnosed at an earlier stage and have a better prognosis than those with other non–small cell lung cancers. Histologically, the tumor morphology is indistinguishable from undifferentiated carcinoma of the nasopharynx. It is characterized by nests or diffuse sheets of syncytial tumor cells, which show round to oval vesicular nuclei with prominent nucleoli, along with an admixed heavy lymphocytic and plasma cell infiltrate. The presence of Epstein-Barr virus in the tumor cells is crucial for the diagnosis. The differential diagnoses include lymphoepithelioma-like carcinoma from other sites and pulmonary involvement of lymphoma. EGFR mutations and ALK rearrangements are not commonly found in lymphoepithelioma-like carcinoma, in contrast to programmed death ligand-1 expression, which is shown in a majority of cases.

Highlights • A synthetic support-bound FRET peptide library was constructed. • This was used to investigate the substrate specificity of recombinant human mitochondrial intermediate peptidase (hMIP). • Polar uncharged residues at P1 and P1′ are preferred by this enzyme. • hMIP can hydrolyse peptides shorter than 8 residues. • The importance of F/L/I at P8 and T/S/G at P5, in natural substrates of hMIP was not seen with this peptide library., The substrate specificity of recombinant human mitochondrial intermediate peptidase (hMIP) using a synthetic support-bound FRET peptide library is presented. The collected fluorescent beads, which contained the hydrolysed peptides generated by hMIP, were sequenced by Edman degradation. The results showed that this peptidase presents a remarkable preference for polar uncharged residues at P1 and P1′ substrate positions: Ser = Gln > Thr at P1 and Ser > Thr at P1′. Non-polar residues were frequent at the substrate P3, P2, P2′ and P3′ positions. Analysis of the predicted MIP processing sites in imported mitochondrial matrix proteins shows these cleavages indeed occur between polar uncharged residues. Previous analysis of these processing sites indicated the importance of positions far from the MIP cleavage site, namely the presence of a hydrophobic residue (Phe or Leu) at P8 and a polar uncharged residue (Ser or Thr) at P5. To evaluate this, additional kinetic analyses were carried out, using fluorogenic substrates synthesized based on the processing sites attributed to MIP. The results described here underscore the importance of the P1 and P1′ substrate positions for the hydrolytic activity of hMIP. The information presented in this work will help in the design of new substrate-based inhibitors for this peptidase.

Somatic angiotensin-I converting enzyme (sACE) is a broadly distributed peptidase which plays a role in blood pressure and electrolyte homeostasis by the conversion of angiotensin I into angiotensin II. N-domain isoforms (nACE) with 65 and 90 kDa have been described in body fluids, tissues and mesangial cells (MC), and a 90 kDa nACE has been described only in spontaneously hypertensive rats. The aim of this study was to investigate the existence of proteolytic enzymes that may act in the hydrolysis of sACE generating nACEs in MC. After the confirmation of the presence of ACE sheddases in Immortalized MC (IMC), we purified and characterized these enzymes using fluorogenic substrates specifically designed for ACE sheddases. Purified enzyme identified as a serine protease by N-terminal sequence was able to generate nACE. In the present study, we described for the first time the presence of ACE sheddases in IMC, identified as serine proteases able to hydrolyze sACE in vitro. Further investigations are necessary to elucidate the mechanisms responsible for the expression and regulation of ACE sheddases in MC and their roles in the generation of nACEs, especially the 90 kDa form possibly related to hypertension.

In order to realize superconductivity in cuprates with the T^{'}-type structure, not only chemical substitution (Ce doping) but also postgrowth reduction annealing is necessary. In the case of thin films, however, well-designed reduction annealing alone without Ce doping can induce superconductivity in the T^{'}-type cuprates. In order to unveil the origin of superconductivity in the Ce-undoped T^{'}-type cuprates, we have performed bulk-sensitive hard x-ray photoemission and soft x-ray absorption spectroscopy on superconducting and nonsuperconducting Nd_{2-x}Ce_{x}CuO_{4} (x=0, 0.15, and 0.19) thin films. By postgrowth annealing, core-level spectra exhibited dramatic changes, which we attributed to the enhancement of core-hole screening in the CuO_{2} plane and the shift of chemical potential along with changes in the band filling. The result suggests that the superconducting Nd_{2}CuO_{4} film is doped with electrons despite the absence of the Ce substitution.

Nonlinear optical frequency conversion has been challenged to move down to the extreme ultraviolet and x-ray region. However, the extremely low signals have allowed researchers to only perform transmission experiments of the gas phase or ultrathin films. Here, we report second harmonic generation (SHG) of the reflected beam of a soft x-ray free-electron laser from a solid, which is enhanced by the resonant effect. The observation revealed that the double resonance condition can be met by absorption edges for transition metal oxides in the soft x-ray range, and this suggests that the resonant SHG technique can be applicable to a wide range of materials. We discuss the possibility of element-selective SHG spectroscopy measurements in the soft x-ray range.

The spin states of Co^{3+} ions in perovskite-type LaCoO_{3}, governed by the complex interplay between the electron-lattice interactions and the strong electron correlations, still remain controversial due to the lack of experimental techniques which can directly detect them. In this Letter, we revealed the tensile-strain dependence of spin states, i.e., the ratio of the high- and low-spin states, in epitaxial thin films and a bulk crystal of LaCoO_{3} via resonant inelastic soft x-ray scattering. A tensile strain as small as 1.0% was found to realize different spin states from that in the bulk.

Problem Ureaplasma species occasionally cause chorioamnionitis and premature labor. We developed a novel assay employing a loop-mediated isothermal amplification (LAMP) method to detect Ureaplasma parvum and Ureaplasma urealyticum. Method of study Loop-mediated isothermal amplification primers were designed to amplify Ureaplasma-specific ureaseB genes. Four U. parvum strains, 5 U. urealyticum strains and 14 reference bacterial species were evaluated. Forty-six vaginal swab samples were analyzed by LAMP, culture, and PCR. Results Our LAMP primers were specific to each species and had no cross-reaction. Of 46 clinical specimens, the sensitivity, specificity, and positive and negative predictive values of the LAMP method were 100% (12/12), 100% (34/34), 100% (12/12), and 100% (34/34), respectively, whereas those of PCR were 66.7% (8/12), 100% (34/34), 100% (8/8), and 89.5% (34/38), respectively, compared to culture-based detection. Conclusion The LAMP detection method outperformed the culture and PCR methods. Early detection enables appropriate antibiotic selection for improved prenatal outcomes.

At the Heavy Ion Medical Accelerator in Chiba (HIMAC), more than 8000 patients have been successfully treated by carbon ion beams since 1994. The successful results of treatments have led us to construct a new treatment facility equipped with a 3-D pencil beam scanning irradiation system. For the implementation of this irradiation technique, we developed a fast scanning magnet and its power supply, which are required to have field ramp rate of more than 250 T/s. The scanning magnets set at the entrance of the irradiation system are two dipole magnets to scan the beam in both horizontal and vertical directions and used to form the irradiation field to be tumor shape. Before the installation, performance test including both static and dynamic field measurement was carried out. Severe delay of the field and temperature rise were not observed as expected. Measured field ramp rate reached up to 300 T/s. After the installation, we verified the accuracy and stability of the scanned ion beam through the commissioning with the beam. As a successful result of the commissioning, treatment using the new scanning system was started in 2011.

Excessive gingival display (EGD) has a negative impact on a pleasant smile. Minimally invasive therapeutic modalities have become the standard treatment in many dentistry fields. Therefore, the aim of this study is to compare the clinical outcomes of open-flap (OF) and minimally invasive flapless (FL) esthetic crown lengthening (ECL) for the treatment of EGD.A split-mouth randomized controlled trial was conducted in 28 patients presenting with EGD. Contralateral quadrants received ECL using OF or FL techniques. Clinical parameters were evaluated at baseline and 3, 6, and 12 months post-surgery. The local levels of receptor activator of nuclear factor-κB ligand (RANKL) and osteoprotegerin (OPG) were assessed by enzyme-linked immunosorbent assay at baseline and 3 months. Patients' perceptions regarding morbidity and esthetic appearance were also evaluated. Periodontal tissue dimensions were obtained by computed tomography at baseline and correlated with the changes in the gingival margin (GM).Patients reported low morbidity and high satisfaction with esthetic appearance for both procedures (P0.05). RANKL and OPG concentrations were increased in the OF group at 3 months (P0.05). Probing depths were reduced for both groups at all time points, compared with baseline (P0.05). There were no differences between groups for GM reduction at any time point (P0.05).FL and OF surgeries produced stable and similar clinical results up to 12 months. FL ECL may be a predictable alternative approach for the treatment of EGD.

Malaria is a disease caused by Plasmodium parasites and remains one of the most prevalent and persistent maladies, affecting hundreds of millions of people. In the present work, we evaluated the capability of Plasmodium falciparum proteases to hydrolyze the multifunctional protein plasminogen, which is implicated in angiogenesis and coagulation processes by the generation of angiostatin and plasmin, respectively. Using fluorescence microscopy, we visualized the internalization of FITC-labeled plasminogen in erythrocytes infected by P. falciparum and showed that the parasites are able to hydrolyze the protein. The cleavage of plasminogen by the P. falciparum proteases was also observed by SDS-PAGE, followed by immunoblotting with anti-angiostatin antibody. N-terminal sequencing of the main generated fragments indicated that they are comprised in the five plasminogen kringle domains, suggesting as being angiostatin-like peptides. This assumption was reinforced by the demonstration that the products of plasminogen processing mimic angiostatin functions, including the capability to inhibit angiogenesis and to stimulate calcium response in endothelial cells in vitro. However, no plasmin activity was detected after plasminogen hydrolysis by P. falciparum. Nonetheless, exogenous tissue plasminogen activator (tPA) activated plasmin in infected erythrocytes, suggesting that the uptake of plasminogen by P. falciparum may be modulated by the vertebrate host. Taken together, the data presented here provide evidence for the processing of host plasminogen by malaria parasites to generate active fragments that may modulate host physiology events during malaria infection.

We present the case of a 64-year-old male with painful swelling of the bilateral testes and epididymides, high fever, leukocytosis, and an elevated C-reactive protein (CRP) level. This is the first case report of testicular diffuse large B-cell lymphoma, not otherwise specified (DLBCL, NOS) immunostained for multiple cytokines and their receptors, which clearly demonstrates that tumor cells express multiple cytokines [interleukin-6 (IL-6) and granulocyte colony-stimulating factor (G-CSF)] and their receptors [IL-6 receptor (IL-6R) and G-CSF receptor (G-CSFR)]. The clinical course showed that the reduction in tumor size was accompanied by a corresponding improvement in clinical symptoms and peripheral blood findings. Such clinical investigation may lead clinicians to misdiagnose inflammatory disease rather than neoplastic disease. Recognizing this paraneoplastic phenomenon associated with some cases of testicular DLBCL, NOS is important. In addition, this case suggests that the growth of tumor cells may be promoted through autocrine mechanisms of IL-6 and G-CSF, which are produced by tumor cells. The possibility that these cytokines can be produced by tumor cells and can accelerate tumor proliferation should be considered to be a cause of severe clinical symptoms, an aggressive clinical course, and an indication of the necessity of treatment. Certain cytokines may be used as tumor markers in some cases of DLBCL, NOS.

Made available in DSpace on 2014-12-03T13:08:43Z (GMT). No. of bitstreams: 0 Previous issue date: 2013-04-01Bitstream added on 2014-12-03T13:24:38Z : No. of bitstreams: 1 WOS000320413900012.pdf: 489453 bytes, checksum: e93398e5a4e4947d5719e007fbb9b25e (MD5) Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Miliin is a serine protease purified from the latex of Euphorbia milii. This work reports the effect of pH and temperature on the catalytic activity of miliin, using fluorescence resonance energy transfer (FRET) substrates. Miliin displayed the highest activity at pH 9 and 35 degrees C. Subsite mapping shows that subsites S-2 to S-2' prefer uncharged residues. The S-2 subsite prefers hydrophobic aliphatic amino acids (Val, Pro and Ile) and defines the cleavage site. This work is the first one that reports subsite mapping of Euphorbiacea proteases. The N-terminal sequence showed higher similarity (40%) with the serine protease LIM9 isolated from Lilium. The presence of Tyr, Pro and Lys at positions 2, 5 and 10 respectively, were observed for most of the serine proteases used for comparison. The N-terminal sequence has striking differences with those reported previously for milin and eumiliin, other serine proteases isolated from the latex of E. milii. (C) 2013 Elsevier Ltd. All rights reserved. State Univ Sao Paulo, IBILCE UNESP, Sao Jose Do Rio Preto, SP, Brazil Univ Sao Paulo, USP, BR-14049 Ribeirao Preto, SP, Brazil Univ Fed Sao Paulo, UNIFESP, Sao Paulo, Brazil State Univ Sao Paulo, IBILCE UNESP, Sao Jose Do Rio Preto, SP, Brazil

The ν1, ν2, and ν3 bands of H2F(+) were observed with a Fourier transform absorption spectroscopic technique in the 3 and 7 μm regions. The ion was produced with a hollow cathode discharge in a F2, He, and H2 gas mixture. A simultaneous analysis of FT data combined with laser spectroscopic data was carried out using the Watson's A-reduced Hamiltonian to determine molecular constants in vibrationally excited states. The effect of the vibration-rotation interaction between the ν1 and ν3 states was found to be small compared with the case of H2O. The vibration-rotation transitions of the ν2 band were first identified and analyzed to obtain molecular constants in the ν2 state, and the band origin was determined to be 1370.5236 (7) cm(-1) with one standard deviation in parentheses. Determined molecular constants can be used to derive the re structure of H2F(+) as re(H-F) = 0.9608(6) Å, ∠e(H-F-H) = 112.2(2)° with the error corresponding to the uncertainty of the assumed vibration rotation constant γ2(a) and the range of the values derived from three pairs of rotational constants.

A thermostable alkaline peptidase was purified from the processing waste of cobia (Rachycentron canadum) using bovine pancreatic trypsin inhibitor (BPTI) immobilized onto Sepharose. The purified enzyme had an apparent molecular mass of 24kDa by both sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and mass spectrometry. Its optimal temperature and pH were 50°C and 8.5, respectively. The enzyme was thermostable until 55°C and its activity was strongly inhibited by the classic trypsin inhibitors N-ρ-tosyl-l-lysine chloromethyl ketone (TLCK) and benzamidine. BPTI column allowed at least 15 assays without loss of efficacy. The purified enzyme was identified as a trypsin and the N-terminal amino acid sequence of this trypsin was IVGGYECTPHSQAHQVSLNSGYHFC, which was highly homologous to trypsin from cold water fish species. Using Nα-benzoyl-dl-arginine ρ-nitroanilide hydrochloride (BApNA) as substrate, the apparent km value of the purified trypsin was 0.38mM, kcat value was 3.14s(-1), and kcat/km was 8.26s(-1)mM(-1). The catalytic proficiency of the purified enzyme was 2.75×10(12)M(-1) showing higher affinity for the substrate at the transition state than other fish trypsin. The activation energy (AE) of the BApNA hydrolysis catalyzed by this enzyme was estimated to be 11.93kcalmol(-1) while the resulting rate enhancement of this reaction was found to be approximately in a range from 10(9) to 10(10)-fold evidencing its efficiency in comparison to other trypsin. This new purification strategy showed to be appropriate to obtain an alkaline peptidase from cobia processing waste with high purification degree. According with N-terminal homology and kinetic parameters, R. canadum trypsin may gathers desirable properties of psychrophilic and thermostable enzymes.

We present the case of an 81-year-old man with primary clear cell sarcoma (CCS) of the pubic bone with an associated aggressive clinical course. The patient's laboratory tests showed marked leukocytosis, elevated levels of C-reactive protein and multiple cytokines, including interleukin-6 (IL-6) and granulocyte colony-stimulating factor (G-CSF). Histological examination showed monomorphic small cells predominantly arranged as a diffuse sheet with morphological features of a small round cell tumor (SRCT). Immunohistochemical staining indicated that the tumor cells were positive for HMB45, S100, Melan A, IL-6, IL-6 receptor, G-CSF, and G-CSF receptor and negative for cytokeratin (AE1/AE3) and epithelial membrane antigen. To the best of our knowledge, this is the first case report of aggressive primary CCS of the pubic bone with features of SRCT showing the production and co-expression of multiple cytokines and their receptors. Thus, we suggest that proliferation through an IL-6- and G-CSF-associated autocrine mechanism may play an important role in the aggressive clinical course and poor prognosis of some CCSs showing features of SRCT.

The objective of this study was to develop a tree mortality predic- tion model using a semi-parametric survival model based on lon- gitudinal data derived from permanent plots. Here, tree mortality data derived from four permanent plots of Cryptomeria japonica planted forest and the Cox proportional hazards model was applied to this data using two time-independent covariates and seven time- dependent covariates. Relative spacing, which is a time-dependent covariate, was selected as the best single predictor for the tree mor- tality model, while, site index, which is a time-independent covari- ate, was better single predictors than other time-dependent variables. Through a model selection procedure, the tree mortality model that included site index (time-independent) and stand density and cumu- lative number of decreased trees (time-dependent) was selected as the best model.