J Bacteriol 2001, 183:5334–5342 PubMedCrossRef 6 Deakin WJ, Park

J Bacteriol 2001, 183:5334–5342.PubMedCrossRef 6. Deakin WJ, Parker VE, Wright EL, Ashcroft KJ, Loake GJ, Shaw CH: Agrobacterium tumefaciens possesses a fourth flagelin gene located in a large gene cluster concerned

with flagellar structure, assembly and motility. Microbiology 1999,145(Pt 6):1397–1407.PubMedCrossRef 7. Chesnokova O, Coutinho JB, Khan IH, Mikhail MS, Kado CI: Characterization of flagella genes of Agrobacterium tumefaciens , and the effect of a bald strain on virulence. Mol Microbiol 1997,23(4):579–590.PubMedCrossRef 8. Götz R, Limmer N, Ober K, Schmitt R: Motility and chemotaxis in two strains of Rhizobium with complex Caspase phosphorylation flagella. J Gen Microbiol 1982,128(4):789–798. 9. Pleier E, Schmitt R: Expression of two Rhizobium meliloti flagellin genes and their contribution to the complex filament structure. J Bacteriol 1991,173(6):2077–2085.PubMed 10. Bergman K, Nulty E, Su LH: Mutations in the two flagellin genes of Rhizobium meliloti . J Bacteriol 1991,173(12):3716–3723.PubMed 11. Cohen-Krausz S, Trachtenberg S: The axial alpha-helices and radial spokes in the core of the cryo-negatively stained complex flagellar filament of Pseudomonas rhodos : recovering high-resolution details from a flexible helical assembly. J Mol Biol 2003,331(5):1093–1108.PubMedCrossRef CT99021 supplier 12. Cohen-Krausz S, Trachtenberg S: Helical perturbations of the

flagellar filament: Rhizobium lupini H13–3 at 13 A resolution. J Struct Biol 1998,122(3):267–282.PubMedCrossRef 13. Namba K, Yamashita I, Vonderviszt F: Structure of the core and central channel of bacterial flagella. Nature 1989,342(6250):648–654.PubMedCrossRef 14. Samatey FA, Imada K, Nagashima S, Vonderviszt F, Kumasaka T, Yamamoto M, Namba K: Structure of the bacterial flagellar protofilament and implications for a switch for supercoiling. Nature 2001,410(6826):331–337.PubMedCrossRef 15. Mimori Y, Yamashita I, Murata K, Fujiyoshi Y, Yonekura K, Toyoshima C, Namba K: The structure of the R-type

straight flagellar filament of Salmonella at 9 A resolution by electron cryomicroscopy. J Mol Biol 1995,249(1):69–87.PubMedCrossRef Thymidylate synthase 16. Mimori-Kiyosue Y, Yamashita I, Fujiyoshi Y, Yamaguchi S, Namba K: Role of the outermost subdomain of Salmonella flagellin in the filament structure revealed by electron cryomicroscopy. J Mol Biol 1998,284(2):521–530.PubMedCrossRef 17. Morgan DG, Owen C, Melanson LA, DeRosier DJ: Structure of bacterial flagellar filaments at 11 A resolution: packing of the alpha-helices. J Mol Biol 1995,249(1):88–110.PubMedCrossRef 18. Hyman HC, Trachtenberg S: Point mutations that lock Salmonella typhimurium flagellar filaments in the straight right-handed and left-handed forms and their relation to filament superhelicity. J Mol Biol 1991,220(1):79–88.PubMedCrossRef 19. Mimori-Kiyosue Y, Vonderviszt F, Namba K: Locations of terminal segments of flagellin in the filament structure and their roles in polymerization and polymorphism. J Mol Biol 1997,270(2):222–237.

Agric Ecosyst Environ 102:175–183 Traill WB, Arnoult MHP, Chamber

Agric Ecosyst Environ 102:175–183 Traill WB, Arnoult MHP, Chambers SA et al (2008) The potential for competitive and healthy food chains of benefit to the countryside. Trends Food Sci Technol 19:248–254 Utsumi SA, Cangiano CA, Gallo JR et al (2009) Resource heterogeneity and foraging behaviour of cattle across spatial scales. BMC Ecol 9. doi:10.​1186/​1472-6785-1189-1189 Vallentine JF (2001) Grazing management, 2nd edn. Academic Press, San Diego

van Groenigen JW, Velthof GL, van der Bolt FJE et al (2005) Seasonal variation in N2O emissions from urine patches: effects of urine concentration, soil compaction and dung. Plant Soil 273:15–27 van Peer L, Nijs I, Reheul D et al (2004) Species richness and susceptibility to heat and drought extremes in synthesized selleck chemical grassland ecosystems: compositional vs physiological effects. Funct Ecol 18:769–778 van Ruijven J, Berendse F (2003) Positive effects of plant species diversity on productivity in the absence of legumes. Ecol Lett 6:170–175 van Wieren SE, Bakker JP (1998) Grazing for conservation in the twenty-first century. In: WallisDeVries MF, Bakker JP, Van Wieren SE (eds) Grazing and conservation management. Kluwer, Dordrecht Villalba JJ, Provenza FD (2009) Learning and dietary choice in herbivores.

Rangel Ecol Manag 62:399–406 Wales WJ, Doyle PT, Dellow DW (1998) Dry matter intake and nutrient selection by lactating cows grazing irrigated pastures at different

pasture allowance in summer and autumn. Aust J Exp Agric 38:451–460 Wang L, Wang D, He Z et al (2010) Mechanisms linking plant species richness to foraging of a large herbivore. J Appl Ecol 47:868–875 Weigelt selleck chemicals A, Bol R, Bardgett RD (2005) Preferential uptake of soil nitrogen forms by grassland plant species. Oecologia 142:627–635PubMed Weigelt A, Weisser WW, Buchmann N et al (2009) Biodiversity for multifunctional grasslands: equal productivity in high-diversity low-input and low-diversity high-input systems. Biogeosciences 6:1695–1706 White SL, Sheffield RE, Washburn SP et al (2001) Spatial and time distribution of dairy cattle excreta in an intensive pasture system. J Environ Qual 30:2180–2187PubMed Whitehead DC (1995) Grassland nitrogen. CAB International, Oxon Whitehead DC (2000) Nutrient elements in grassland. CAB International, Wallingford Wilmshurst Farnesyltransferase JF, Fryxell JM, Bergman CM (2000) The allometry of patch selection in ruminants. Proc R Soc Lond B Biol Sci 267:345–349 Yachi S, Loreau M (1999) Biodiversity and ecosystem productivity in a fluctuating environment: the insurance hypothesis. Proc Natl Acad Sci USA 96:1463–1468PubMed”
“Introduction The spruce bark beetle, Ips typographus (Col., Curculionidae, Scolytinae), is an important insect species of Picea abies in Europe. The estimation of I. typographus population density is of high theoretical and practical significance for nature conservation and forestry. I.

The DNA region containing the final 121 bp of the ftsZ ORF and 28

The DNA region containing the final 121 bp of the ftsZ ORF and 28 bp after the termination codon (coordinates 7267 to 7415) was amplified with the primers Eco3 and Bam3 (Table 1) that carry EcoRI and BamHI sites, respectively, and was restricted. Plasmid pJPR1 [9] (‘amyE cat P xyl amyE’ bla, a gift from J. Rawlings) was digested with HindIII and BamHI in the polylinker region, ligated to the prepared DNA fragments and transformed into E. coli Hb101. The correct recombinant plasmid was chosen by sequencing and used to transform competent B. subtilis 168. The ftsZ minigene

became integrated at the amyE site as a result of a double crossing-over event between the 5’ and 3’ amyE regions carried upstream and downstream

of the cloning site in pJPR1. Integration was controlled by sequencing. RNA transcribed from the minigene in the recombinant B. subtilis 168 was detected by primer extension Poziotinib with primer Amy5 (Table 1) annealing to the 5’ region of the amyE locus, 245 nucleotides downstream of the inserted minigene. Induction of the pxyl promoter by 5% xylose in TS was for 18 h and 3 h. Termination sequences The putative B. mycoides termination sequences were detected on the basis of their identity to those predicted for B. weihenstephanensis at the TransTerm-HP site (http://​transterm.​cbcb.​umd.​edu .). The region of the B. weihenstephanensis KBAB4 genome considered was from coordinates 3780796 to 3790953 (Accession NC_010184), containing the genes of the dcw cluster from murD to ftsZ and the following spoIIG operon. Sequence data Sequences of the B. mycoides

SIN and DX partial learn more dcw clusters are deposited as GenBank AY129554 (SIN) and AY129555 (DX). Acknowledgements This work was supported by the Italian Space Agency with ASI contract n° 1/R/290/02 and ASI-MoMa project 2006–2009 to EB. Institutional funds for EB came from the CNR Istituto di Biologia e Patologia Molecolari IBPM. Science Faculty funds from the Sapienza University of Rome supported CDF. We thank Giuseppe Pisaneschi for his valuable technical assistance. Electronic supplementary material Additional file 1: Putative initiation sites of ftsQ , ftsA and ftsZ Florfenicol RNA as determined by primer extension. The gene sequences are those of the B. mycoides DX strain (accession AY12555.2). The DNA complementary to the PE primers is highlighted in turquoise, as are the nucleotides of RNA start. Initiation and termination codons of the ORFs are in red. The hexamers corresponding to consensus TATA-box promoter motifs (17) and the ribosome binding sites are underlined. (PPTX 142 KB) Additional file 2: Determination of SpoIIGA RNA 5’ ends by Primer Extension. The three genes of the SpoIIG cluster are encoded downstream of the dcw cluster, by the same DNA strand. The distance between the two clusters is 415 bp in DX and 260 bp in SIN.

We decided not to compare the findings obtained in our study sinc

We decided not to compare the findings obtained in our study since it resulted from a different experimental procedure. Russian authors [36] demonstrated that intensification of the training regimes in an Olympic judo team with the exercise of anaerobic

character leads to a significant development of special endurance, accompanied by a reduction in aerobic capacity. The judoists training, with fighting bouts of intermittent character, caused integration of anaerobic and aerobic capacity. According to Thomas et al. [10] “judo may be a unique sport in that not only must effort be required equally of upper and lower body, but the training process must require a fine integration between aerobic and anaerobic training.” Based on the Autophagy Compound Library evaluation of energy consumption during performing the SJFT test, with its temporal structure and character of movements imitating a fight, the energy cost depends on utilization of the alactic and lactic anaerobic systems and the aerobic system. The alactic

energy system presented a higher contribution when compared with both aerobic and lactic energy systems, and the lactic energy system had a lower contribution compared to the aerobic system [37]. Therefore, it seems undisputable that training regimes should periodically incorporate an improvement in a variety of aspects of physical capacity in judoists. Conclusions The multifaceted judo training Protein Tyrosine Kinase inhibitor is conducive to the development of both FM and FMI. Use of supplementation of the diets with creatine malate does not cause an increase in body mass greater than in the control group. Shorter time to obtain peak power toPP is conducive to faster execution of rapid planned actions in attack or defense. Pre and post-training aerobic power did not change so it was not supplementation-dependent. Creatine malate did not affect the results in SJFT. There are many determinants of the judo fight results e.g. technical,

tactical, physiological and psychological factors, one of them could be supplementation but it can not be treated as a separate improving factor. The significant improvement in Total Throws in SJFT with the unchanged Index in SJFT suggests better neuromuscular adaptations Edoxaban compared to those occurring in circulatory and respiratory systems. The results obtained during the SJFT test depend not only on energy resources but also on the exercises which improve the technique of performing typical grip-and-throw judo actions, despite the ensuing fatigue. References 1. Warchała A, Kucia K, Małecki A: Znaczenie kinazy kreatynowej w psychiatrii – prawda i mity. Wiadomości Lekarskie. LIX 2006,3(4):255–260. 2. Baird MF, Graham SM, Baker JS, Bickerstaff GF: Creatine-kinase-and exercise-related muscle damage implications for muscle performance and recovery. J Nut Met 2012, 1–13. http://​www.​hindawi.​com/​journals/​jnume/​2012/​960363/​ 3. Clark JF: Creatine and phosphocreatine: a review of their use in exercise and sport.

Despite the fact

Despite the fact learn more that the authors used another mosquito strain in their studies, they also used a non-EGFP expressing virus and higher virus concentrations in their bloodmeals, ranging from 108-109 pfu/ml. In our study the virus concentrations in bloodmeals ranged from 1.7-2.7 × 107 pfu/ml. In the presence

of a functional RNAi mechanism as in HWE mosquitoes, the lower virus concentration in the bloodmeal was probably approaching the threshold for midgut infection. In the RNAi pathway impaired Carb/dcr16 mosquitoes however, this virus concentration was sufficient to cause productive midgut infections. Between 7 and 14 days pbm a strong reduction of virus infection intensity was observed in midguts of Carb/dcr16 mosquitoes, causing

a decrease in average SINV titers from 14,000 to 2400 pfu/ml. Such strong reduction of virus infection intensity was not observed in the RNAi pathway competent HWE control. After 7 days pbm Autophagy signaling pathway inhibitors the RNAi pathway in Carb/dcr16 mosquitoes was no longer compromised as it was during virus acquisition. It appears that the RNAi mechanism, when functional, down-regulated the unusually high SINV concentration in midguts of the transgenic mosquitoes to levels similar to those of the HWE control. This strongly suggests that the task of the RNAi pathway in the mosquito midgut is to keep arbovirus replication at a level that can be tolerated by the mosquito. Modulation of arbovirus infections in mosquitoes has been reported for several virus-vector combinations and research of the last

few years eventually confirmed that the RNAi pathway of the mosquito is a major driving force behind this modulation [2, 3, 6, 14, 16, 32]. Nevertheless, recent studies indicate that other innate immune pathways, such as JAK-STAT and/or Toll also contribute to the modulation of arbovirus infections in insects [33–37]. Since a proposed role for the RNAi pathway in mosquitoes is to protect the insect selleckchem from pathogenic effects of replicating arboviruses [4–6], we investigated whether SINV-TR339EGFP causes such effects in HWE or Carb/dcr16 mosquitoes. Our survival curve data indicate that the initial increase in virus titer in Carb/dcr16 females did not cause obvious pathogenic effects. It needs to be pointed out that after 7 days pbm the RNAi pathway was no longer impaired in midguts of Carb/dcr16 mosquitoes and the intensity of infection was strongly modulated. Thus, the RNAi pathway activation in the transgenic mosquito line could have been similar to that in the control for the latter 21 days of the survival study. Our observations confirm those by Campbell and co-workers [3] that transient silencing of the RNAi pathway in Ae. aegypti did not affect longevity of the mosquitoes for seven days after infection with SINV. However, several authors have described pathological effects caused by alphaviruses in mosquito midguts and salivary glands, claiming that these effects could be virus dose-dependent [38–41].

Some of these transcription factors are known to be involved in p

Some of these transcription factors are known to be involved in positive regulation of gene expression (LuxR, AraC). Others are involved in repression (DeoR, MerR), while members of IclR and LysR families could be activators or repressors of gene expression [22]. Nevertheless, the contribution of these regulators and

their targets to B. melitensis internalization epithelial cells has not been fully examined. The locus encoding the alternative sigma 32 factor (BMEI0280) that allows Brucella to survive under general stress situations was up-regulated in stationary phase cultures. The BMEI1789 locus that encodes a subunit of the other alternative sigma 54 factor (rpoN), which allows transcription of those genes involved in utilization Y-27632 in vivo of nitrogen and carbon sources and energy metabolism, was up-regulated in late-log phase cultures compared to stationary phase cultures. Two-component transcriptional regulators are comprised of a cytoplasmic membrane-located sensor protein and a cytoplasmic response regulator protein [23]. Eight ORFs encoding for two-component response regulators have been identified in the B. melitensis 16 M genome [19]. Raf inhibitor review One of the signal transduction-encoded genes up-regulated in late-log phase cultures (vsr; BMEI1606), was previously identified in B. melitensis attenuated mutants [24]. The other

(hprK; BMEI2034) is a central regulator of carbohydrate metabolism genes and also plays a role in virulence development of certain pathogens [25]. Although the molecular regulation Acyl CoA dehydrogenase of these response regulators in B. melitensis is currently unknown, understanding how vsr, hprK and others are regulated, could offer insight into B. melitensis virulence. Identifying the target genes of these transcriptional regulators would significantly clarify the role of growth-phase in Brucella physiology, metabolism and virulence regulation. Almost all differentially expressed genes encoding cell envelope and outer membrane components were up-regulated in late-log phase cultures The ability of Brucella to invade cells has been linked to its outer membrane (OM) properties, as well as to structures built within

the cell envelope [26, 27]. Twenty-six genes directly involved in cell envelope and outer membrane biogenesis were differentially expressed at late-log compared to stationary phase of growth. These included genes that encode outer membrane proteins (BMEI0402, BMEI0786), lipoproteins (BMEI0991, BMEI1079), LPS (BMEI0418, BMEI0586, BMEI0833, BMEI1414), and peptidoglycan biosynthesis (BMEI0271, BMEI0576). The main COGs functional category of genes that were up-regulated in B. melitensis cultures at late-log compare to stationary phase of growth were ORFs encoding membrane transport proteins. These included genes encoding transporters specific for amino acids (BMEI0263–0264, BMEII0098–9 and BMEII0861 to II0864), carbohydrates (BMEI1580, BMEI1713, BMEII0621–2 and II0624) and uncharacterized transporters (BMEI1554, BMEII0481, BMEII0483, BMEII0662).

2 nd, not determined; alphanumeric nomenclature as defined by Pav

2 nd, not determined; alphanumeric nomenclature as defined by Pavlik et al., 1999 [17], alphabetic nomenclature correspond to new profiles identified in this study. 3 Nomenclature as defined by Stevenson et al., 2002 [8]. 4 Nomenclature as defined by Thibault et al., 2007 [11]. 5 Number of repeats at locus 292-X3-25-47-3-7-10-32

defined by Thibault et al., 2007 [11]. 6 +, presence; -, absence. IS900-RFLP method Map strains were typed by IS900-RFLP as Temsirolimus mouse described previously [11]. Profiles were designated according to nomenclature previously described [17, 20–22]. Profiles were analysed using Bionumerics™ software version 6.5 (Applied Maths, Belgium). PFGE analysis PFGE analysis was carried out using SnaBI and SpeI according to the published standardized procedure of Stevenson et al. [8] with the following modifications. Plugs were prepared to yield a density of 1.2 × 1010 cells ml-1 and the incubation time in lysis buffer was increased to 48 hr. The concentration of lysozyme was increased to 4 mg ml-1. Incubation with proteinase K was carried out for a total of seven days and the enzyme was refreshed after four days. Restriction of plug DNA by SpeI was performed with 10U overnight after which the enzyme was refreshed

and incubated for a further 6 hr. The parameters for electrophoresis of SpeI restriction X-396 mw fragments were changed to separate fragments of between 20 and 250Kb as determined by the CHEF MAPPER and electrophoresis was performed for 40 hr. Gel images were captured using an Alphaimager 2200 (Alpha Innotech). Profiles were analysed using Bionumerics™ software version 6.5 (Applied Maths, Belgium). SNP analysis of gyrA and gyrB genes Primers (Additional file 2: Table S2) were designed for both gyrA (GenBank accession no. 2720426

[Genome number: NC_002944.2]) and gyrB genes (GenBank accession no. 2717659 [Genome number: NC_002944.2]). The PCR mixture was composed as follows using the GoTaq Flexi DNA polymerase (Promega). Two microliters of DNA Tau-protein kinase solution was added to a final volume of 50 μl containing 0.2 μl of GoTaq Flexi DNA polymerase (5 U/μl), 2 mM (each) dATP, dCTP, dGTP, and dTTP (Promega); 10 μl of 5x PCR buffer supplied by the manufacturer; 1 μM of each primers; and 1.5 mM of MgCl2. The reactions were carried out using a TC-512 thermal cycler (Techne). PCR conditions were as follows: 1 cycle of 5 min at 94°C; 30 cycles of 30 s at 94°C, 30 s at 58°C, and 30 s at 72°C; and 1 cycle of 7 min at 72°C. PCR products were visualized by electrophoresis using 1.5% agarose gels (agarose electrophoresis grade; Invitrogen), purified using NucleoSpin® Extract II (Macherey-Nagel) and sequenced by GenomExpress (Grenoble, France). Sequence analysis and SNP detection were performed by using the Bionumerics™ software version 6.5 (Applied Maths, Belgium). LSP analysis Primers were used according to Semret et al.

The extreme N-terminal region of FliH is very poorly conserved, b

The extreme N-terminal region of FliH is very poorly conserved, but some sequence conservation is evident in the various bacterial groups (e.g. enterobacteria, epsilon proteobacteria),

but not the YscL protein family. A GxxxG segment of variable length follows, then a poorly conserved segment likely to be helical in structure, followed by a well-conserved C-terminal domain known to be responsible for Fostamatinib manufacturer the interaction with the N-terminus of the flagellar/Type III ATPase (Figures 1, 2 and 3). When we noticed the presence of conserved consecutive GxxxG repeats in FliH/YscL, we asked if this motif had been previously observed in other types of proteins. Lemmon et al. [22] first discovered that specific interactions are required for the transmembrane helix-helix dimerization of glycophorin A. It was later shown that dimerization was mediated by a GxxxG-containing motif [23]. The GxxxG motif has been identified as the dominant motif in the transmembrane regions of hundreds of proteins [24, 25], and appears to play a critical role in the stabilization of helix-helix interactions. Such motifs were subsequently observed in many soluble proteins [26]. The amino acid composition of the variable positions in the glycine repeats of soluble proteins is certain to be very different from that of transmembrane proteins; transmembrane proteins would contain mostly hydrophobic residues in the variable positions of the repeats, while the variable

positions in soluble proteins would contain mostly find more hydrophilic residues. As such, the only commonality between glycine repeats in transmembrane proteins and glycine repeats in soluble proteins is likely to be the glycines found

at every fourth residue. As glycine lacks a side chain, it is suitable for allowing the close packing of helices, and could hence facilitate helix-helix dimerization. Most annotated FliH sequences contain a segment of repeats of the form AxxxG(xxxG) m xxxA, where m can vary on average between 2 and 10 depending on the bacterial Rebamipide species. While there is some variation to this pattern, not all sequences contain the N-terminal-side Axxx or the C-terminal-side xxxA, and FliH proteins from some species have no GxxxG repeats at all. Nevertheless, a significant proportion (44% in our set of sequences) of FliH proteins extracted from the non-redundant sequence database (see Methods) do exhibit the AxxxG(xxxG)mxxxA pattern. In addition to this long AxxxG(xxxG) m xxxA repeat segment, most FliH proteins also contain one or more shorter repeat segments elsewhere in the primary sequence (Figures 1, 2 and 3), which usually contain just a single AxxxG, GxxxG, or GxxxA. These shorter repeat segments are very poorly conserved, do not contain an obvious preference for particular amino acids at any of the three middle non-glycine positions, and often contain proline. Hence, these non-conserved GxxxG segments are unlikely to be either helical or biologically significant.

In the Fracture Intervention study, alendronate was shown to redu

In the Fracture Intervention study, alendronate was shown to reduce the incidence of vertebral, wrist and hip fractures by approximately half in women with prevalent vertebral fractures [173–175]. In women without prevalent vertebral fractures,

there was no significant decrease in clinical fractures in the overall population, but the reduction was significant in one third of patients that had a baseline hip BMD T-score lower than −2.5 SD [176]. Risedronate in women with prevalent vertebral fractures has been shown to reduce the incidence of vertebral and non-vertebral fractures by 40–50 and 30–36 %, respectively [177, 178]. In a large population of elderly women, risedronate decreased significantly the risk of hip fractures (by 30 %), an effect that was greater in osteoporotic women aged EMD 1214063 supplier 70–79 years (−40 %), while the decrease was not significant in women over the age of Epacadostat clinical trial 80 years without documented evidence of osteoporosis [71]. Ibandronate given daily (2.5 mg) reduces the risk of vertebral fractures by 50–60 %, whereas an effect on non-vertebral fractures was only demonstrated in a post hoc analysis of women with a baseline of BMD T-score below −3 SD [179–181]. Bridging studies have shown that oral ibandronate 150 mg once monthly is equivalent or superior to

daily ibandronate in increasing BMD and decreasing biochemical markers of bone turnover, giving rise to its approval for the prevention of vertebral fracture in postmenopausal osteoporosis [182]. Similarly, bridging studies comparing intermittent intravenous

ibandronate to daily oral treatment C-X-C chemokine receptor type 7 (CXCR-7) have led to the approval of intravenous ibandronate 3 mg every 3 months for the same indication [183]. Based on the result of a phase II study [184], a large phase III trial in over 7,700 postmenopausal osteoporotic patients assessed the efficacy of yearly infusion of zoledronic acid 5 mg over 3 years. As compared to the placebo group, zoledronic acid was found to reduce the incidence of vertebral fractures by 70 % and that of hip fractures by 40 % [185], and is now available for the treatment of postmenopausal osteoporosis. Intravenous zoledronic acid has also been shown to decrease the risk of fracture and mortality when given shortly after a first hip fracture [186]. The overall safety profile of bisphosphonates is favourable. Oral bisphosphonates are associated with mild gastrointestinal disturbances, and some aminobisphosphonates (alendronate and pamidronate) can rarely cause oesophagitis. Intravenous amino-bisphosphonates can induce a transient acute-phase reaction with fever and bone and muscle pain that ameliorates or disappears after subsequent courses [187]. Osteonecrosis of the jaw has been described in cancer patients receiving high doses of intravenous pamidronate or zoledronate.

We suppose that the formation of such directed microstructure on

We suppose that the formation of such directed microstructure on a surface of samples will create conditions when closed vacuum valleys in the contact zone either will not be formed at all or will be easily and quickly devacuumized. As a result, it should lead to substantial reduction friction force and surface wear. Figure 3 Special surface structure consisting of parallel grooves proposed for wear reduction. Experimental study Ball-bearing

steel grade ShH15 (according find more to the standard GOST 801-78) produced by electroslag remelting has been chosen as a material for fabrication of samples. It has international analogues: American AISI Type E52100, UNS G52986, European 100Сr6, and Japanese JIS SUJ2. This high-carbon chromium steel features high hardness, high mechanical strength, and dimensional stability. Tribological tests were carried out on the friction machine with a fixed flat-surface sample and a rotating cylindrical counterface sample. The oil IMP-10 was used as a lubricant. A special technique for forming grooves on a sample surface with specified 3D geometry was developed. Initially, the surface of the sample was polished to a level of roughness with Ra about 0.02 μm. Then, diamond paste with size of a grain corresponding to the desired depth of grooves

was applied. Movement BAY 73-4506 of a polishing plane with diamond paste was performed only in one direction. Polishing with the paste actually led to controllable scratching of the surface. Polishing movements were repeated only a few times to preserve the initial nano-topography of the surface between grooves. Intermediate results were checked by the laser differential phase profilometer [10] and scanning electron microscope. As a result, ten flat samples with directional grooves had been fabricated. The depth of grooves was varied in the range

Fluorouracil nmr from 0.3 to 2.6 μm. Rotating cylindrical counterface had no grooves on it, and surface roughness was the same as the initial roughness of samples Ra = 0.02 μm. A multistage testing technique which mimics operation conditions of real friction units was developed. The testing procedure of each sample included the following: (1) three initial run-in stages, in which the formation of secondary structures on friction surfaces occurred; (2) the final test stage, during which tribological and rheological characteristics of a friction samples and lubricant were estimated. Each of the initial three stages was run until a length of friction equals L = 500 m. The final measurement stage had a length of friction L = 3,000 m. Ambient temperature was 20°С. Axial load 1,250 N was big enough to maintain permanent wear but not to allow plastic deformation of material.