We explored the Zr1-xHfxB2 system with first-principles cluster expansion and thermodynamic analysis of possible reactions targeting the synthesis in vacuum-thermal conditions. The results suggest that the system may have a slight tendency to ordering but at high temperatures the formation of solid solutions is driven by the entropy of mixing. We realized the synthesis of an equimolar composition (x = 0.5) by sintering of ZrB2 and HfB2 and reduction from oxides by boron with varying homogenization of the reacting mixtures. The temperature of the complete transformation strongly depended on the reactants homogeneity and was 1900 degrees C for more coarse raw materials and below 1700 degrees C for a fine hydrothermal mixture of oxides. The possibility of producing nonequimolar compositions of the solid solutions by the same method was also experimentally demonstrated.
The article is dedicated to the study of wetting and specifics of interaction between phases on the "drop-substrate" interface in the AIB(12)-Al system. Contact angles between an aluminum melt and an aluminum dodecaboride ceramic substrate were studied using the sessile drop method. It was found that upon aluminum melting at 660 degrees C, contact angles are Theta > 90 deg. Intensive spreading of the aluminum melt starts at 1200 degrees C with contact angles Theta approximate to 15 deg. The X-ray spectral microanalysis showed that AIB(12) grains recrystallized through the aluminum melt on the interface. In addition, due to the absence of active chemical interaction, the AIB(12)-Al system can be recommended for the development of new composite materials.
The European XFEL is a hard X-ray free-electron laser (FEL) based on a high-electron-energy superconducting linear accelerator. The superconducting technology allows for the acceleration of many electron bunches within one radio-frequency pulse of the accelerating voltage and, in turn, for the generation of a large number of hard X-ray pulses. We report on the performance of the European XFEL accelerator with up to 5,000 electron bunches per second and demonstrating a full energy of 17.5 GeV. Feedback mechanisms enable stabilization of the electron beam delivery at the FEL undulator in space and time. The measured FEL gain curve at 9.3 keV is in good agreement with predictions for saturated FEL radiation. Hard X-ray lasing was achieved between 7 keV and 14 keV with pulse energies of up to 2.0 mJ. Using the high repetition rate, an FEL beam with 6 W average power was created. The first operation of the European X-ray free-electron laser facility accelerator based on superconducting technology is reported. The maximum electron energy is 17.5 GeV. A laser average power of 6 W is achieved at a photon energy of 9.3 keV.
Reactions of aluminum dodecaboride synthesis from oxygen free industrially available boron compounds by interaction of condensed and gaseous aluminum with boron nitride and carbide were the subject of thermodynamic analysis in this work. It was shown, that both reactions are thermodynamically advantageous at low temperatures rather than at high and the probability of their occurrence rises significantly for gaseous aluminum in comparison with condensed aluminum. Calculated values of Gibbs’ free energy and equilibrium constants and the analysis of contributions into them clearly demonstrate the advantages of reaction with boron nitride. The probability of polyphase product composition imposes minimum temperature restrictions on the synthesis; it should be carried out at temperatures above 1000 ℃. Hypothetical mechanisms of reactions between aluminum and boron containing compounds differ by the place of interaction — any place on the surface of each layer of BN and only open surface of B4C — and by the transport of reaction participants in the reaction zone. From the results of analysis, we suggest indicative synthesis conditions: vacuum thermal synthesis to provide oxygen free environment and temperature above 1000 ℃ to avoid aluminum diboride formation.
Sarcoidosis is a systemic, inflammatory disorder, which in a proportion of patients runs a chronic progressive course despite immunosuppressive treatment. Therapeutic granulocyte and monocyte apheresis (GMA) has been shown to be an effective treatment option for other systemic inflammatory disorders, but has not yet been investigated in sarcoidosis. The aim of this study was to evaluate the response to GMA in sarcoidosis. Seven patients with sarcoidosis refractory to standard immunosuppressive therapy received 10 GMA sessions. All patients underwent chest X-ray, spirometry, a Chronic Respiratory Disease Questionnaire (CRQ-SAS), blood tests and bronchoscopy with bronchoalveolar lavage (BAL) before treatment and at 2-4 weeks and 3 months (except bronchoscopy) after the last treatment session. Bronchoalveolar lavage fluid (BALF) cell differential counts were recorded and T cells from blood and BALF were analysed for markers of activity, differentiation and T regulatory function. Compared to baseline, five of seven patients reported an improvement in dyspnoea score. In BALF there was an increase in the percentage of macrophages and a decrease in the percentage of lymphocytes and CD4(+) /FoxP3(+) T cells. Furthermore, the decrease in BALF CD4(+) /FoxP3(+) T cells correlated significantly with an improvement in dyspnoea score. In peripheral blood there was a statistically significant increase in the percentage of CD4(+) /CD27(-) T cells and a trend towards an initial increase in the percentage of CD4(+) /FoxP3(+) T cells, followed by a statistically significant decrease. The effects of GMA on regulatory T cells are consistent with those observed in other inflammatory disorders and could potentially translate into a clinical benefit.
Leukocyte apheresis primarily used for treatment of inflammatory diseases such as inflammatory bowel disease (IBD). Beside an effect of the apheresis column, the plastic lines in the apheresis system might also have an effect due to interaction between the plastic surfaces and circulating leukocytes and plasma proteins. We recently reported generation of LL‐37 in the plastic lines during leukocyte adsorbing apheresis. This generation might have a positive impact on the immunologic tolerance and therefore be one operational mechanism by which the apheresis treatment executes its effect. In the present study, we report a significant generation of sIL‐1RI in the apheresis lines that is initially absorbed by the LCAP device. This finding, together with our previous data on IL‐1Ra indicate that important members of the IL‐1 family are significantly altered during the LCAP treatment of patients with IBD. Since IL‐1 and its antagonists are important for regulation of inflammatory processes in IBD, we speculate that the LCAP related changes in sIL‐1RI and IL‐1Ra might impact the clinical outcome. These findings have to be taken into consideration when designing new apheresis techniques as well as sham‐controlled studies. J. Clin. Apheresis, 2012. © 2012 Wiley Periodicals, Inc.
Cellsorba™ is a medical device for leukocytapheresis (LCAP) treatment of ulcerative colitis (UC). Cellsorba™ EX Global type has been developed from Cellsorba E for intended use with ACD‐A as anticoagulant. We evaluated safety and efficacy of the modified Cellsorba using ACD‐A in a pilot trial comprising patients with active UC, despite receiving 5‐ASA. A total of 10 LCAP treatments/patients were administered. Safety assessment focused on clinical signs and symptoms, hematological variables, as well as levels of bradykinin and IL‐6. Efficacy was determined using the Mayo clinical/endoscopic scoring index as well histological assessment of biopsies. Additional aim was to evaluate the impact of apheresis system lines and filter on selected regulatory molecules. All six subjects completed the trial without any serious adverse events. WBC, platelet counts, and levels of bradykinin and IL‐6 were not significantly affected. The median Mayo score decreased from 8.0 to 3.5 at week 8 (and to 2 at week 16 for the responders). Four patients were responders, of whom two patients went into remission. Median histological scores decreased from 3.5 to 2.0 in these four patients. Concentration of LL‐37 increased within the apheresis system lines. LCAP with Cellsorba EX using ACD‐A as anticoagulant was found to be a safe and well‐tolerated procedure in patients with active UC. The positive impact on efficacy parameters merits further evaluation in a controlled fashion. J. Clin. Apheresis, 2010. © 2010 Wiley‐Liss, Inc.
Experimental study results of silica glass luminescence in optical range under bombardment by molecular hydrogen ions owith energy 420 keV are presented. The effect of H-2(+) dose absorbed in the silica sample on the luminescence spectrum shape has been studied. A calibrating curve for remote control of absorbed dose in the silica glass has been obtained.
We have studied a role of immunological balance in connection to allergen challenge in asthma patients and in connection to apheresis treatment in inflammatory bowel disease (IBD) patients. It has been suggested that T-helper type 2 cells become recruited into the bronchial mucosa and regulate allergic asthma reaction. Patients who mounted a late-phase reaction in connection to allergen challenge were designated dual responders opposite to single responders. Our finding that IL4+CD4+ cells decreased in the patient group and IFN-γ + CD4+ cells decreased in the single responders after allergen challenge suggests the active traffic of both Th1 and Th2 cells into bronchial mucosa. A diminished capacity to down-regulate the Th2 response by recruitment of sufficient number of IFN-γ positive CD4+ lymphocytes was suggested as explanation to the late phase symptoms in the dual responders. A previously proposed mechanism of granulocyteand monocyte adsorbing apheresis (GMA) is that in removing activated granulocytes and monocytes the production of pro-inflammatory cytokines, predominantly TNF-α will be reduced. Following GMA in patients with chronic, active IBD, IFN-γ-positive lymphocytes decreased in post-treatment biopsies in responders and appeared to predict the maintenance of long-term remission or response after 12 months. The finding of down regulation of IFN-γ+CD4+ cells in post-treatment blood samples and IFN-γ+ cells in post-treatment biopsies indicates that the mechanisms of GMA are complex and may influence the Th-balance. Given that FoxP3+ T regulatory cells and Toll Like Receptor (TLR) expression are key actors in mucosal immunoregulation we extended the previous study to identify the dynamics of these actors in the intestinal mucosa in relation to clinical improvement following GMA. The number of FoxP3+ cells and TLR-2 expression significantly decreased in post-treatment biopsies. The down regulation of FoxP3+ cells and TLR-2 expression mirrored clinical improvement in patients with active IBD after GMA. The results suggest a potential role of these cells in the pathogenesis of IBD and the induction of immunological tolerance in the mucosa. The effect of apheresis system lines on soluble regulatory molecules (which are important for the immunological balance) has not been studied before, but was assessed on selected regulatory molecules during a safety study on a modified Cellsorba (device for leukacytapheresis (LCAP)). An important observation was that LL-37 increased at all apheresis sessions within the apheresis plastic lines. LL-37 is a major constituent of neutrophil granules. The peptide mediates a wide range of immunomodulatory actions (microbicidal and chemokine for granulocytes, monocytes, mastcells and T lymphocytes, it suppresses TLR-induced secretion of proinflammatory cytokines) and may therefore have a positive impact on the immunological tolerance and which may contribute to LCAP efficacy on UC. In summary: We have suggested that differences in response to allergen can depend on different capacity to maintain and restore the immunological balance in bronchial mucosa, the Th-balance. Diminished capacity to recruit IFN-γ+ CD4+ lymphocytes is associated with development of an additional so called late-phase reaction. We have demonstrated that one plausible mechanism of GMA are immunomodulating involving down regulation of IFN-γ+ lymphocytes hereby influencing the Th-balance. The clinical improvement in IBD after GMA was associated with improved immunological tolerance mirrored by down regulation of FoxP3+ cells and TLR-2 expression. And finally, we have described generation of LL-37 in the plastic lines of apheresis system, which may also have a positive effect on the immunologic tolerance. The results emphasize that the restoration of the immunological tolerance can be a key to future successful therapeutic strategy. LIST OF PUBLICATIONS I. Muratov V, Barck C, Bylin G, Kallstrom E, Hallden G, van Hage M, Elvin K, Lundahl J. Allergen challenge alters intracellular cytokine expression. Scand J Immunol. 2005; 62(2):161-7. II. Muratov V, Lundahl J, Ulfgren AK, Elvin K, Fehrman I, Ost A, Hittel N, Saniabadi A, Lofberg R. Downregulation of Interferon-γ Parallels Clinical Response to Selective Leukocyte Apheresis in Patients with Inflammatory Bowel Disease. A 12-Month Follow-up Study. Int J Colorectal Dis 2006; 21: 493-504. III. Muratov V, Ulfgren A-K, Engstrom M, Elvin K, Winqvist O, Lofberg R, Lundahl J. Decreased numbers of FoxP3 positive and TLR-2 positive cells in intestinal mucosa are associated with improvement in patients with active inflammatory bowel disease following selective leukocyte apheresis. J Gastroenterology 2008; 43:277-282. IV. Muratov V, Lundahl J, Mandic-Havelka A, Elvin K, Ost A, Shizume Y, Furuya K, Lofberg R. Safety and tolerability of a modified filter-type device for leukocytapheresis using ACD-A as anticoagulant in patients with mild to moderately active ulcerative colitis. Results of a pilot study. J Clin Apheresis 2010; 25(5):287-293.
BACKGROUND:Impaired immunological tolerance to commensal enteric flora is considered one possible pathogenic mechanism of inflammatory bowel disease (IBD). Given that regulatory T cells and Toll-like receptor (TLR)-positive cells are key actors in mucosal immune regulation, we aimed to identify the dynamics of these actors in the intestinal mucosa in relation to clinical improvement following selective leukapheresis treatment.METHODS:Ten patients with active IBD despite treatment with corticosteroids, immunomodulators, or anti-tumor necrosis factor therapy were assessed by immunohistochemical staining of colorectal mucosal biopsies obtained before and after five sessions (week 7) of granulocyte and monocyte adsorption apheresis (GCAP). The presence of FoxP3-positive regulatory T cells, macrophages, dendritic cells, and TLR-2 and-4 positive cells was determined in relation to short-(week 7) and long-term (week 52) clinical outcome data.RESULTS:Following GCAP, the number of FoxP3-(P = 0.012) and TLR-2 (P = 0.008)-positive cells significantly decreased in biopsies after 7 weeks, in parallel with both clinical improvement at week 7 and a longstanding response after 12 months.CONCLUSIONS:Downregulation of FoxP3 and TLR-2 cells in the colorectal mucosa mirrors both short-and long-term improvement in patients with active IBD responding to GCAP. This observation suggests a potential role of these cells in the pathogenesis of IBD and the induction of immunological tolerance in the mucosa.
A capacitor cell of a capacitive energy storage designed for operating with an arc load is described. The cell that stores an energy of 64 kJ is based on a high-voltage (18 kV) capacitor and allows formation of current pulses with an amplitude of up to 60 kA. The discharge circuit of the cell contains a semiconductor switch in the form of an assembly of reverse switch-on dynistors (RSDs) connected in series, a crowbar diode switch, and a replaceable toroidal inductor. An assembly of protecting diodes connected in series to the RSD switch excludes the possibility of a flow of reverse-current pulses through dynistors. All elements of the cell are mounted on the capacitor and occupy a volume of 120 dm3.
Summary form only given. The capacitor cell of the large energy storage intended tor operation into the arc load is considered. The 64 kJ capacitor cell made on the basis of the 400muF, 18kV capacitor of the AVX company' (TPC, France) makes it possible to generate current pulses with an amplitude up to 60 kA. The cell discharge circuit is arranged as a pulse forming network composed of a semiconductor switch made as a connected-in- series reversal switched dynistor (RSD), a crowbar diode switch and a replaceable toroidal inductor of 25 muH, 40 muH or 80 muH inductance. An assembly of powerful protecting diodes is connected in series with the RSD switch to prevent the passing of the reverse current through the RSD switch. All components of the cell (the semiconductor switches, the ballast and the grounding resistors, the replaceable inductor, the elements of the control system, etc.) are assembled on the top cover of the capacitor. The description of the RSD trigger circuit is presented. The generation of output current pulses is considered for synchronous triggering of the cells and non-simultaneous triggering in the programmable discharge mode. The protection elements of the semiconductor switches are considered. The results of the cell testing are presented.
Forward and backward secondary electron emission induced by normal incidence of 1.5 MeV protons from 5 mu m copper foil was experimentally studied. Measurements were carried out by means of two low-aperture retarding field energy analyzers. Electron distribution functions were measured in 0...90 eV energy interval. The comparative analysis of electron distribution for forward and backward cases was performed and possible reasons for the differences observed were discussed.
Pilot studies have indicated a therapeutic role for an apheresis device (Adacolumn) that selectively adsorbs leukocytes in patients with inflammatory bowel diseases. It may also exert immunoregulatory effects contributing to its clinical efficacy. This study aimed to correlate the clinical response to leukocyte apheresis with the expression of key cytokines in mucosal tissue, in peripheral leukocytes, and in plasma.
The work has been carried out at the Efremov Institute according to the new PETRA-III machine optics. Normal-conducting magnets (quadrupole, dipole and corrector magnets) for the PETRA-III project were designed and calculated. Prototypes were built and magnetic measurements were carried out. Two precision quadrupole magnets with asymmetrical yoke lengths were developed. Their apertures are 70 mm and their design gradients 21.5 T/m. The integral field nonlinearity in the good field region (GFR), r o < 25 mm should be less than 0.0005. The new dipole magnets for the PETRA-III project have a H-shaped magnetic yoke with a length of 1 m. In the GFR area of 60 mm times 36 mm a magnetic field of B max = 1 T should be obtained. Within the GFR limits the integral field nonlinearity should be less than 0.0005, which is achieved by profiling the poles (longitudinal chamfers, slants and shims). The vertical correction dipole magnet has a horizontal magnetic field of B X = 0.062 T, its aperture is 112 mm times 50 mm and its total length, including the coil end parts, is limited to L = 200 mm. The authors have designed two versions one with air-cooling and one with water-cooling. Results of the magnetic measurements are given and compared with the simulation
Three versions of hybrid quadrupoles 2a0=15mm in aperture with shunting elements made of soft magnetic material (SMM) are analyzed. It is shown that Version 1 allows for gradient variation in the range of G=40-90 T/m and the regulation of magnetic center at Gmax during the rotation of external ring with shunting inserts. Authors have also analyzed the possibility to regulate the position of quadrupole magnetic axis by rotating additional rods made of hard magnetic material (HMM). The analysis has revealed that in Version 2 the radial displacement of shunts and components of their sections affect the magnetic parameters of the quadrupole. Finally, Version 3 of hybrid yokeless quadrupole is considered. The gradient variation and magnetic center regulation are provided by the radial displacement of HMM pole parts
The pathophysiology of asthma is complex and engages cascades of events in the cytokine network. We, therefore, investigated the impact of bronchial allergen challenge in humans on the cytokine profile of circulating lymphocytes. Peripheral blood samples from 10 patients with allergic asthma were collected before and 24 h after allergen provocation. Patients who mounted a late-phase reaction were designated dual responders opposite to single responders. Whole blood cells were stimulated by mitogen and intracellular interleukin (IL)-4 and interferon (IFN)-gamma were detected by flow cytometry. The allergen challenge induced a decrease in IL-4(+)CD4(+) cells in the patients (P = 0.05), and a significant decrease (P < 0.05) in IFN-gamma(+)CD4(+) cells was noted in single, but not dual, responders. In addition, there was a significant difference (P < 0.01) with respect to the changes in the IFN-gamma(+)CD4(+) cells comparing dual and single responders. No corresponding changes were observed in CD8(+) cells. The data suggest a possible on-going traffic of IFN-gamma and IL-4(+)CD4(+) lymphocytes into the bronchial mucosa in relation to an allergen challenge and generate the hypothesis that a difference exists between single and dual responders in this respect. Because the CD4(+)IFN-gamma-producing cells have the capacity to downregulate the T-helper type 2 response, a reduced capacity in this aspect might contribute to the pathophysiology in dual responders.