ANALYTIC SOLUTION FOR SELF-REGULATED COLLECTIVE ESCAPE OF COSMIC RAYS FROM THEIR ACCELERATION SITES.

Supernova remnants (SNRs), as the major contributors to the galactic cosmic rays (CRs), are believed to maintain an average CR spectrum by diffusive shock acceleration regardless of the way they release CRs into the interstellar medium (ISM). However, the interaction of the CRs with nearby gas clouds crucially depends on the release mechanism. We call into question two aspects of a popular paradigm of the CR injection into the ISM, according to which they passively and isotropically diffuse in the prescribed magnetic fluctuations as test particles. First, we treat the escaping CR and the Alfvén waves excited by them on an equal footing. Second, we adopt field-aligned CR escape outside the source, where the waves become weak. An exact analytic self-similar solution for a CR "cloud" released by a dimmed accelerator strongly deviates from the test-particle result. The normalized CR partial pressure may be approximated as P ( p , z , t ) = 2 [ | z | 5 / 3 + z dif 5 / 3 ( p , t ) ] - 3 / 5  exp [ - z 2 / 4 D ISM ( p ) t ] , where p is the momentum of CR particle, and z is directed along the field. The core of the cloud expands as z dif ∝ D NL ( p ) t and decays in time as P ∝ 2 z dif - 1 ( t ) . The diffusion coefficient D NL is strongly suppressed compared to its background ISM value D ISM: D NL ~ D ISM exp (-Π) ≪ D ISM for sufficiently high field-line-integrated CR partial pressure, Π. When Π â‰« 1, the CRs drive Alfvén waves efficiently enough to build a transport barrier ( P ≈ 2 / | z | - "  pedestal " ) that strongly reduces the leakage. The solution has a spectral break at p = p br, where p br satisfies the equation D NL ( p br ) ≃ z 2 / t .

Proton-helium spectral anomaly as a signature of cosmic ray accelerator.

The much-anticipated proof of cosmic ray (CR) acceleration in supernova remnants must hinge on the full consistency of acceleration theory with the observations; direct proof is impossible because of CR-orbit scrambling. Recent observations indicate deviations between helium and proton CR rigidity spectra inconsistent with the theory. By considering an initial (injection) phase of the diffusive shock acceleration, where elemental similarity does not apply, we demonstrate that the spectral difference is, in fact, a unique signature of the acceleration mechanism. Collisionless shocks inject more He(2+) when they are stronger and so produce harder He(2+) spectra. The injection bias is due to Alfvén waves driven by the more abundant protons, so the He(2+) ions are harder to trap by these waves. By fitting the p/He ratio to the PAMELA data, we bolster the diffusive shock acceleration case for resolving the century-old mystery of CR origin.

Mechanism for spectral break in cosmic ray proton spectrum of supernova remnant W44.

Recent observations of supernova remnant W44 by the Fermi spacecraft observatory support the idea that the bulk of galactic cosmic rays is accelerated in such remnants by a Fermi mechanism, also known as diffusive shock acceleration. However, the W44 expands into weakly ionized dense gas, and so a significant revision of the mechanism is required. Here, we provide the necessary modifications and demonstrate that strong ion-neutral collisions in the remnant surrounding lead to the steepening of the energy spectrum of accelerated particles by exactly one power. The spectral break is caused by Alfven wave evanescence leading to the fractional particle losses. The gamma-ray spectrum generated in collisions of the accelerated protons with the ambient gas is calculated and successfully fitted to the Fermi Observatory data. The parent proton spectrum is best represented by a classical test particle power law ∝E(-2), steepening to E(-3) at E(br)≈7 GeV due to deteriorated particle confinement.

[Effect of inoculum parameters on the specificity of secondary synthesis in cultures producing novobiocin and mycoheptin]. / Vliianie kharakteristik posevnogo materiala na napravlennost' vtorichnogo sinteza produtsentov novobiotsina i mikogeptina.

The impact of the vegetative inoculum parameters on specificity of the secondary synthesis in the cultures producing novobiocin and mycoheptin was studied. During the study the fermentation conditions were varied by using the vegetative inoculum differing in the respiration rate after its transfer to the fermentation medium. To show the decisive role of the inoculum parameters in regulation of the specificity of the secondary synthesis, the dynamics of accumulation of certain metabolites forming from glucose along with the main antibiotic and the activity of the key enzymes of the carbohydrate metabolism during the culture growth in the fermentation media were studied. It was found that the specificity of the secondary synthesis with respect to certain metabolites was defined by the intensity of carbohydrate metabolism, i. e. the ratio of the activity of enzymes of glycolysis and the pentosephosphate pathway. In this regard, the inoculum with the maximum respiration rate in an amount of 10 to 20 per cent promoted the highest productivity of the mycelium by the synthesis of novobiocin and mycoheptin while the rate of accumulation of fatty acids, carbohydrates and phenol compounds (for Streptomyces spheroides) and mycopentene (for Streptoverticillium mycoheptinicum) decreased.

[Study of biosynthesis of mycoheptin, mycopentene and fatty acids by Streptoverticillium mycoheptinicum strain 255 in various conditions of its cultivation]. / Issledovanie biosinteza mikogeptina, mikopentena i zhirnykh kislot v razlichnykh usloviiakh kul'tivirovaniia Streptoverticillium mycoheptinicum shtamm 255.

The effect of the fat content in the medium for cultivation of Streptoverticillium mycoheptinium-255 and the effect of glucose intake on the rate of carbohydrate utilization and intensity of incorporation of labeled sodium acetate and propionate to mycoheptin, mycopentene and fatty acids were studied. It was shown that a lower fat content in the medium in comparison with the optimal one resulted in intensification carbohydrate catabolism during an idiophase, increased production rates of mycopentene, an accompanying antibiotic, and fatty acids and a decrease in the heptaene/pentaene ratio. The optimal contents of the oil in the medium provided a decrease in the rate of the carbohydrate consumption and preferable production of the required antibiotic or mycoheptin accompanied by a decrease in the synthesis rate of mycopentene and fatty acids.

[Effect of the producer type on the nature of antibiotic fermentation]. / Vliianie tipa produtsenta na kharakter fermentatsii antibiotikov.

Fermentation processes in production of bacitracin, a polypeptide antibiotic by Bacillus licheniformis, and oleandomycin, a macrolide antibiotic by Streptomyces antibioticus, were studied comparatively. It was shown that the antibiotic-producing actinomycete was characterized by a prolonged phase of growth retardation. The highest efficiency of the control actions was observed at the beginning of the fermentation. They were aimed at intensifying the substrate usage during the growth phase and activation of cell metabolism. Controlled cultivation of the Bacillus representative was based on its capacity of achieving the maximum growth rate possible under the certain conditions. Therefore, an increase in the quantity of the synthesized antibiotic was due, under such conditions, to inhibition of the culture growth by various means including lower mass exchange intensity.

[Application of a method of material-energy balance for controlling the process of microbiological synthesis of riboxin]. / Primenenie metoda material'no-énergeticheskogo balansa dlia upravleniia protsessom mikrobiologicheskogo sinteza riboksina.

Possible control of riboxin biosynthesis on the basis of the information provided with the method of material-energy balance was studied. Correspondence of the cultivation conditions to the directed biosynthesis was established by comparing the experimental values of the respiration coefficient delta CO2/delta O2, the coefficient of constructive and energy metabolism conjugate Cc/e and the ratio of the consumed amounts of glucose and ammonium nitrogen delta S/delta NH4+ with the theoretical values of these parameters. The control principle included changing of the process operation parameters for providing cultivation conditions approximating the experimental values of Cc/e, delta CO2/delta O2 and delta S/delta NH4+ to their theoretical values. It was shown possible to control directed aerobic growth of the culture by changing the aeration conditions. A decrease in the initial aeration rate promoted more rapid transition of the microbial population to the exponential growth phase and provided for a certain period cultivation conditions corresponding to the conditions of conjugate metabolism. It was found that the respiration coefficient could be used not only as a parameter reflecting one of the forms of the cell physiological activity manifestation but also as an optimization criterion in development of a controlled cultivation process.

[Influence of the intensity of oxygen mass transfer on the biosynthesis of amphotericin B]. / Vliianie intensivnosti massoperedachi kisloroda na biosintez amfoteritsina B.

Influence of oxygen mass transfer intensity characterized by the rate of oxygen dissolution (S) and the agitation rate (n), as well as influence of dissolved oxygen concentration on the process of amphotericin B biosynthesis was studied. It was shown that S = 40 and 110 mg/l. min and n = 450 and 800 min-1 were respectively the lower and the upper levels of the optimal conditions by oxygen mass transfer during amphotericin B biosynthesis. When biosynthesis of amphotericin B was conducted under conditions of the optimal oxygen mass transfer, the dissolved oxygen concentration of about 12 to 15 per cent of the saturation level was critical for the culture respiration. Inhibition of the culture respiration and antibiotic synthesis was induced under conditions of increased oxygen mass transfer intensity (S greater than 110 mg/l. min and n greater than 800 min-1) by high intensity mechanical agitation of the fermentation broth. Under conditions of decreased oxygen mass transfer (S less than 40 mg/l. min and n = less than 450 min-1) it was induced by insufficient supply of oxygen to the culture. On the basis of the results it was shown possible to control the aeration and agitation conditions by the rate of oxygen uptake and dissolved oxygen concentration. The data should be considered in optimization of aeration and agitation conditions in biosynthesis of amphotericin B in large fermenters.

[Effect of surface-active agents (tween-21) on indices of energy metabolism in oleandomycin producers]. / Vliianie poverkhnostno-aktivnykh veshchestv (tvina-21) na pokazateli énergeticheskogo obmena u produtsenta oleandomitsina.

The specific growth rate of Streptomyces antibioticus, a producer of oleandomycin, and the specific rate of the antibiotic accumulation in the culture medium during fermentation were investigated. On the basis of the results obtained the fermentation period was divided into 7 phases of development. The culture treated with the surfactant (Tween-21) is characterized by a higher specific growth rate during the whole fermentation and a higher specific rate of the antibiotic accumulation at the stage of the highest production as compared to the control. The ATP content, the value of the adenylate energy charge and the contents of high-molecular weight polyphosphates in the mycelium were examined. In the phase of the intensive growth St. antibioticus was characterized by a higher ATP level and a higher energy charge. More active accumulation of polyphosphates was observed in the late intensive growth phase. It was also found that after the treatment of the culture with Tween-21 it utilized polyphosphates more actively during the antibiotic biosynthesis.

[Effect of surface-active substances on carbohydrate metabolism in the producer of oleandomycin]. / Vliianie poverkhnostno-aktivnykh veshchestv na metabolizm uglevodov u produtsenta oleandomitsina.

Activity of glucose-6-phosphate dehydrogenase (I), fructose diphosphate aldolase (II) and succinate dehydrogenase (III) and content of pyruvate (IV) in the mycelium of the oleandomycin-producing organism were studied during increased intensity of the antibiotic synthesis. The increase in the intensity of the antibiotic synthesis was induced by exposure of the spores to a surface active substance, twin-21. After the exposure a rise in the activity of all the three enzymes in the phase of the culture intensive growth was observed. During the antibiotic intensive production the cultures with increased antibiotic production levels were characterized by significantly higher activity of I as compared to the control while the activity levels of II and III were approximately the same. It was shown that concentration of IV in the mycelium during the antibiotic intensive biosynthesis decreased and the decrease was more pronounced after exposure to twin-21.

[Characteristics of the oleandomycin producer inoculum at various levels of antibiotic biosynthesis]. / Kharakteristika posevnogo materiala produtsenta oleandomitsina pri razlichnoi intensivnosti biosinteza antibiotika.

Parameters of the oleandomycin-producing organism metabolism were studied at the stage of inoculum when intensity of the antibiotic biosynthesis was increased by treating the spores with a surface active substance (twin-21). It was shown that the inoculum producing later at the stage of fermentation higher quantities of the antibiotic was characterized by certain peculiarities. In particular, there were observed a shorter lag phase, a higher specific growth rate and a higher rate of accumulating the medium components at lower pyruvate levels in the exponential phase, higher activity of succinate dehydrogenase and higher levels of ATP in the mycelium during this period.

[Assessment by the material and energy balance method of the directed biosynthesis of riboxin by altering the external culture conditions]. / Otsenka metodom material'no-énergeticheskogo balansa napravlennogo biosinteza riboksina pri izmenenii vneshnikh uslovii kul'tivirovaniia.

The effect of various agitation conditions on growth of the cell population of Bacillus subtilis and production of riboxin was studied. The physiological state of the culture was estimated by the relations for the respiration coefficient CO2/O2, the yield of the constructive metabolism products (X + P) by oxygen Yx + p/O2, the ratio of consumed glucose to ammonium nitrogen S/NH4+, the coefficient of the cell biosynthetic activity Yp/x and the parameter of the energetic efficiency of the substrate usage (eta). It was shown that the maximum biosynthetic activity was mainly defined by the culture state in the trophophase. The growth of the cell population in this case should proceed under conditions of conjugated aerobic metabolism. It was found that directed biosynthesis of riboxin could be provided by changing the cultivation conditions and estimation of the culture physiological state by the parameters of the material and energy balance.

[Oxidation-reduction status of the culture medium during the biosynthesis of amphotericin B]. / Izuchenie okislitel'no-vosstanovitel'nogo sostoianiia kul'tural'noi zhidkosti v protsesse biosinteza amfoteritsina B.

The possibility of potentiometric estimation of the oxidation-reduction state of the fermentation broth during production of amphotericin B was studied. It was shown that the reduction capacity of the fermentation broth was high and did not change significantly during the antibiotic biosynthesis. It contained electrochemically active compounds in amounts providing stable potentials on the indicator electrodes. Both the platinum and the glass redoxmetric electrodes not sensitive to changes in the level of oxygen dissolved in the fermentation broth might be used for measuring the oxidation potential of the fermentation broth. Investigation of the dynamics of the oxidation potential changing revealed that during the process of amphotericin B biosynthesis the potential changed within wide ranges and every stage of the culture development was characterized by particular direction of the potential changing. This allowed, in combination with other parameters of the process, estimation of physiological activity of the culture at any moment of its growth.

[Cyclic adenosine-3',5-monophosphate in Streptomyces antibioticus and its possible role in regulating oleandomycin biosynthesis and the growth of the culture]. / Tsiklicheskaia adenozin-3',5-monofosfornaia kislota u Strptomyces antibioticus i ee vozmozhnaia rol' v reguliatsii biosinteza oleandomitsina i rosta kul'tury.

When glucose is substituted for sucrose in the fermentation medium for Streptomyces antibioticus, the pH of the cultural broth becomes more acidic, the rate of protein synthesis in the mycelium rises, and the rate of oleandomycin synthesis decreases abruptly. The dynamics of cAMP (cyclic monophosphate) accumulation was studied in the process of biosynthesis by the culture in different media. Most of the synthesized cAMP (80-90%) was shown to be excreted into the medium. Glucose stimulates cAMP synthesis and excretion from the mycelium by a factor of 1.5-3. No distinct correlation was found between cAMP content in S. antibioticus cells and the level of oleandomycin biosynthesis. A correlation between changes in the concentration of exocellular cAMP and protein synthesis in the mycelium suggests that the excreted cAMP may be involved in regulating the growth of the culture producing the antibiotic.

[Inhibition of oleandomycin biosynthesis by glucose]. / Podavlenie biosinteza oleandomitsina gliukozoi.

The results of the study on the effect of glucose and various carbohydrates on biosynthesis of oleandomycin by Streptomyces antibioticus are presented. It was found that glucose added at the beginning or by the 48th hour of the fermentation process on the complex medium inhibited oleandomycin biosynthesis. To investigate the mechanism of the glucose effect, a fermentation medium was developed. It provided variation of the carbohydrate composition, determination of the protein content in the culture and evaluation of the mycelium productivity. With the use of this medium it was shown that monosaccharides such as galactose, fructose and glucose significantly activated the mycelium growth as compared to lactose and sucrose. At the same time glucose completely inhibited oleandomycin biosynthesis when added either as an only carbohydrate component or in combination with galactose or fructose, while the presence of the other two monosaccharides did not prevent antibiotic production, though the mycelium productivity was lowered as compared to that with the use of the disaccharide. Therefore, the inhibitory effect of glucose on biosynthesis of oleandomycin was not connected with activation of the culture growth by it. Acidification of the medium on cultivation of the streptomycete in the presence of glucose only partially explained its inhibitory effect, since inhibition was maintained on the medium with addition of CaCO3 which stabilizes pH. Addition of 2-deoxy-D-glucose, a nonmetabolized glucose analog, to the fermentation medium retarded antibiotic production. It is possible that the inhibitory effect of glucose on biosynthesis of oleandomycin is not associated with its metabolism.

[Dynamics of the biosynthesis of nystatin components by Act. noursei, strain 153 under controlled culture conditions]. / Dinamika biosinteza komponentov nistatina v upravliaemykh usloviiakh kul'tivirovaniia Act. noursei, shtamm 153.

The ratio of the nystatin components produced under various cultivation conditions was studied. It was found to change during the greater part of the fermentation period and depend on the carbohydrate content in the medium. Under the conditions of the uncontrolled batch process the ratio of components A1 and A2 during the first 36 hours of the cultivation changed from 7.2 to 6.2. When the rate of the antibiotic synthesis was maximum (42 - 72 hours), the ratio of A1 and A2 components was practically constant and equal to 5.5 - 5.2. Beginning from the 72nd hour, when the rate of nystatin synthesis decreased, the ratio of A1 and A2 components increased up to 6.6 - 9.0. Periodical addition of high amounts of glucose during the idiophase promoted activation of the synthesis of the less active A1 component. On momentous addition of glucose in the amounts of 1, 2 and 3 per cent the ratio of A1 and A2 components increased by the end of the process up to 14.3, 16.6 and 22.4 respectively. The data suggest that the nystatin components and especially the active A2 component which is more stable on storage are sensitive to accumulation of glucose catabolites.

[Biosynthesis of the components of levorin and fatty acids in the process of Str. levoris cultivation]. / Izuchenie biosinteza komponentov levorina i zhirnykh kislot v protsesse kul'tivirovaniia Str. levoris.

The rate of incorporation of the labeled precursors, acetate and propionate, into levorin components and fatty acids was studied. It was shown that within the first 12 hours of cultivation the rate of labeled precursors incorporation into levorin components A2, A3, A0 and A1 was low. In this period the acetate and propionate labeled with respect to the methyl and carboxyl groups mainly incorporated into fatty acids. A higher rate of acetate incorporation as compared to propionate at the beginning of cultivation suggested that acetate was the first link of the chain. At the beginning of the idiophase, i.e. during the period of 36 to 48 hours of cultivation, the rate of incorporation of the carboxyl and methyl groups of the labeled precursors into the levorin components increased. The rate of incorporation of the radioactive precursors into components A2 and A3 markedly increased after 72 hours of cultivation. The maximum rate of incorporation of the carboxyl and methyl groups of acetate and propionate into components A0 and A1 was observed somewhat earlier, i. e. by the 48th hour of cultivation. During the period from 72 to 96 hours of cultivation the incorporation rate of the labeled precursors for components A2 and A3 was constant and then gradually decreased. The radioactivity of components A0 and A1 was constant during the period of 48 to 72 hours of cultivation and then gradually decreased. Beginning from the 24th hour of cultivation the level of 14C-propionate incorporated into all levorin components was higher than that of 14C-acetate incorporation. After 96 hours of cultivation the rate of 2-14C-propionate incorporation into the levorin components was higher than that of 1-14C-propionate incorporation.

[Effect of carbon and nitrogen source additions on the development of a productive strain of P. nigricans Thom and on the level of adenylates in its mycelium]. / Vliianie dobavok istochnikov ugleroda i azota na razvitie produktivnogo shtamma P. nigricans Thom i uroven' adenilatov v ego mitselii.

Growth of the cultured strain og P. nigricans and dynamics of the adenylate levels in its mycelium on mineral media with 2 per cent of glucose were studied in relation to the means and time of addition of glucose, NaNO3 or their mixture to the medium. It was shown that the maximum yield of the mycelium could be obtained with addition of glucose once at the moment of inoculation. The mixture of glucose with NaNO3 provided even higher yields of the biomass but only with its fractional addition. Introduction of additional amounts of NaNO3 at the moment of inoculation and during the growth phase (5 days) inhibited the subsequent development of the culture providing stable levels of ATP and ADP, while introduction of NaNO3 on the 7th day stimulated the culture growth and the antibiotic yield. The use of NaNO3 in the mixture with glucose eliminated inhibition and increased the ratio of ATP to ADP and the antibiotic yield.

[Adenylate level in the mycelium of Penicillium nigricans Thom. grown on various carbon sources]. / Uroven' adenilatov v mitselii shtammov Penicillium nigricans Thom., vyrashchivaemykh na raznykh istochnikakh ugleroda.

Concentrations of ATP and ADP and their dynamics during cultivation (2, 5, 9 and 13 days) of a highly productive strains of P. nigricans on a mineral medium in the presence of various carbon sources, such as glucose, succinate or acetate were studied. It was shown that the levels of ATP and ADP in the mycelium depended on the carbon source: the maximum and minimum ATP concentrations were found on the glucose and acetate media respectively, the maximum and minimum ADP concentrations showed inverse dependence. The concentrations of both adenylates on the same carbon source depended on the strain. The dynamics of the adenylates levels during cultivation showed an analogous dependence on the carbon source and the strain. Thus, the highly productive strain was characterized by a constant ATP level on glucose and succinate and variation on acetate, while the ADP level was characterized by a decrease by the 9th day of cultivation on any of the carbon sources. The low productive strain was characterized by variations in the level of ATP in any media used, stability of the ADP level by the 2nd--9th day of cultivation on the glucose medium and by the 2nd--5th day of cultivation on the succinate medium and a decrease by the 9th day of cultivation on the acetate and succinate media. The ratio of ATP/ADP at the phase of griseofulvin biosynthesis (9 days) markedly increased in both the strains when cultivated on the media with any of the carbon sources.