Regional and widespread outbreaks were reported in the Republic of Korea and Japan in January. Low-level activity was reported in Europe from September to November but increased during December and January in many countries. In northern Africa, activity increased in January with widespread outbreaks reported in Algeria. Sporadic and localised A(H3N2) activity was also reported in Oceania, central (Cameroon) and southern Africa and a number of countries in South America. Influenza B virus activity increased in North America from November with regional outbreaks reported by Mexico and the United States of America

and was predominant in Mexico. In Europe, widespread outbreaks were reported in many countries in January. In Asia activity was generally low. Localised and sporadic B activity Stem Cells inhibitor was also reported by a number of countries in Africa, Oceania and South America. Influenza activity maps (maximum level of activity shown) for the period August 2012–January 2013 along with graphs showing the number of influenza viruses detected, typed and subtyped by the GISRS laboratories from 2010 to 2013 are presented in Fig. 1. At the time of the VCM, data collected from the GISRS laboratory network showed

that, of the influenza viruses collected from September 2012 to February 2013, SB203580 in vivo approximately 92,298 (77%) were type A and 27,695 (23%) type B; of the type A viruses 14,306 (15.5%) were A(H1N1)pdm09, 47,213 (51.2%) were A(H3N2) and 30,779 (33.3%) were not subtyped. For the Consultation, WHO CCs performed detailed antigenic analyses on 3147 influenza viruses (Table 1). Viruses were collected from September 2012 to the beginning of February 2013 and recovered from either clinical specimens or virus isolates provided by NICs and other laboratories within and outside GISRS. Antigenic characterisation was carried out predominantly by haemagglutination inhibition (HI) assays using viruses isolated and propagated in either mammalian

tissue culture cells (most frequently Madin-Darby canine kidney cells not (MDCK) or MDCK-SIAT-1 cells, the latter engineered to express increased levels of α-2,6 sialyl transferase [2]) or in embryonated hens’ eggs. HI assays using turkey or guinea pig red blood cells (RBC) were performed to compare the reactivity of cultured viruses with post-infection ferret antisera raised against egg- or cell-propagated reference viruses [3]. A subset of viruses also underwent genetic characterisation. Genetic analyses were focused on the sequencing of the haemagglutinin (HA) and neuraminidase (NA) genes, with matrix (M) gene or full genome sequencing performed on a smaller subset of viruses.

used poxvirus Crizotinib for boosting and the soluble factor(s) secreted by MVA may not or less affect the expression of

poxvirus itself. Viral interference was discovered several decades ago. Co-infection of cells with two replication-competent viruses results in suppression of replication of both viruses. The Ad and MVA vectors used in this study were not capable of replicating in mice and human. Therefore, we infected A549 cells (a human epithelial cell line, which can be infected by both Ad and MVA vectors without viral replication) with a GFP-expressing MVA vector and an mCherry-expressing Ad vector. We found that most of the cells were infected with only an individual virus (Fig. 3d), indicating that interference caused by the co-administration of the Ad vector and MVA vector may be different from that caused by dual replication-competent find more viral infection. To explore transgene expression, we co-infected A549 cells with a SEAP-expressing Ad vector and a GFP-expressing MVA vector. As shown in Fig. 3a and b, the MVA vector down-regulated the transgene expression produced by the Ad vector. Furthermore,

similar results were observed when the Ad-SEAP-infected A549 cells were incubated with a supernatant of the MVA-GFP-infected cells (Fig. 3c). This indicated that MVA vector-infected A549 may secrete soluble factor(s) that would cause suppression of Ad vector transgene expression. Recent studies have shown that bacterial and viral infection in cells results in the secretion of type I IFN via toll-like receptor, dependant or independent of the innate immune pathway [31], [32] and [33]. To explore whether innate immunity is involved in viral interference, we infected the A549 cells with Ad or MVA and detected the mRNA of IFNα, IFNβ, and IFNγ at various time points between 0 and 96 h post infection (Fig. 4a). The mRNA of IFNα and IFNγ MycoClean Mycoplasma Removal Kit was not detected at any point of time; however, only a small amount of IFNβ mRNA was detected after 40 cycles of PCR, indicating that type I IFN may have not had much influence on our results. A further study confirmed our conclusion, since blocking of IFNβ in the supernatant of the MVA-infected cells did not bring about recovery of Ad transgene expression

(Fig. 4b). In summary, we co-administered Ad-HIV and MVA-HIV or their mock vectors to mice, and observed the suppression of HIV-specific effector T-cell responses and a part of memory T cell responses, compared to vaccination with either of the vaccines alone. An in vitro experiment indicated that viral interference may involve other soluble factor(s) besides type I IFN. Our study may help in designing a vaccination regimen and in investigating viral interference in the future. We thank NIH Tetramer Core Facility (Atlanta, GA) for tetramers. This work was partially supported by a Grant-in-Aid from the Ministry of Education, Science, Sports and Culture of Japan. “
“The past 5 years have been a period of extraordinary achievement in the rotavirus field.

Mammary carcinoma results from the undifferentiated growth of mammary cells associated with different conditions

such as disturbances in TCA cycle i.e. down regulation of TCA cyclic enzymes, non-glycolytic enzymes and up regulations of glycolytic enzymes. These 2 factors produce HIF-ALPHA and leads to induction of anti apoptotic genes in the cell nucleus, also cause the hypoxia condition to the cell. It causes activation of angiogenesis by activation if VEGF at the same time oxidative stress and free radical reactions. With these consequences finally lead to oxidative stress resulting in increase resistance to therapy has been seen in breast cancer. Hence Trametinib the present study was concerned on the synthesis of the quinazolinone-4-one derivatives for a potent active. The melting point and Rf value of the synthesized compound conformed the purity and reaction completion. Then the compounds were subjected to spectral analysis the analytical data showed satisfactory results. The in-vitro antioxidant activity of quinazolinone derivative was assessed carried by different methods. DPPH radical is scavenged by antioxidants through the donation of proton forming the reduced DPPH. 12 Electrons become paired off and the solution loses color stoichiometrically depending on the number of electrons taken up. The radical scavenging activity of the newly synthesized quinazolinone derivative was evident at

all the concentrations but only at moderate level not as significant as that of standard much quercetin. The scavenging activity of the compound was increased LY2157299 mw with increase in concentration of quinazolinone-4-one derivative and that of the standard. The ABTS method is based on the technique that ABTS react with potassium per sulfate and produces a blue green color due to the formation of ABTS radical

cation (ABTS+). 13 The nitric oxide generated from sodium nitroprusside, when reacted with oxygen forms nitrite which is inhibited by antioxidants by competing with oxygen for nitric oxide14 which then interacts with oxygen to produce nitrate ions that can be estimated. The % inhibition showed an increase as the concentration increases. The tested compound Qc showed a potent scavenging activity than other compounds while others showed a moderate activity. Super oxides are produced from molecular oxygen due to oxidative enzymes of body as well as non-enzymatic reaction such as autoxidation by catecholamine. In this study super oxide radical reduced from NBT to a blue color compound formazan. The decreased absorbance indicates the consumption of super oxide anion in the reaction mixture. Free radicals induce lipid peroxidation in polyunsaturated lipid rich areas like brain and liver. In this study in-vitro lipid peroxidation was induced to rat liver by using the thiobarbituric acid assay is based on the reaction of TBA with malondialdehyde MDA, one of the aldehyde products of lipid peroxidation.

Amphoterecin-B and Ketoconazole were used as the reference antifungal agent. The result revealed that most of newly synthesised 3,4,5-triarylisoxazole compounds exhibited good antifungal activities against F. oxysporus and C. albicans. We synthesised a series of Novel 3,4,5-triarylisoxazoles derivatives in high yields. The advantages are the usage of low cost starting selleck compound chemicals and simple experimental

procedure. These derivatives are having good antifungal activity. All authors have none to declare. The authors express their thanks to Islamiah College, Vaniyambadi for the laboratory facilities provided to carry out the research work. “
“La dystrophie myotonique de type 1 est la myopathie la plus fréquente chez l’adulte. Le risque de développer une tumeur est plus élevé chez les patients atteints de dystrophie myotonique que dans la population générale. “
“Although most pharmacognostic studies focus on plants, other types of organisms are also regarded as pharmacognostically interesting. Euglena gracilis is a microalgae member of the Euglenoids,

that can grow autotrophically, heterotrophically or Compound Library myxotrophically that it has been extensively studied, 1 and 2 mainly on primary metabolites production, 3, 4 and 5 but little is known about secondary metabolites biosynthesis. The most startling findings about this species concern to 4α-methylsterols, detected in trace amounts. 6 and 7E. gracilis has a wide range of nutritional requirements, suggesting the existence Isotretinoin of diverse physiological patterns, generating different metabolites and/or variation in the proportion they are biosynthesised. The aim of this work is to carry out a preliminary study on two strains of E. gracilis cultured in vitro,

both in their photosynthetic and bleached forms, on their exponential and stationary growth phase. The Euglena reserve polysaccharide paramylon has been previously shown to have general antitumoral properties and reduce the negative effects of stressors. 8 and 9 Since paramylon precipitates in ethanol, our work explores the antioxidant and antitumoral in vitro effect of the extracts in its absence. Two E. gracilis strains were used: a commercial (UTEX-753) and a wild type strain (MAT) isolated from Matanza River. 10 Studies were performed on the photosynthetic (ph) strains and their bleached (b) counterparts, obtained by treatment with streptomycin. The cultures were grown in a growth chamber at 24 ± 1 °C, with 12:12 cool-white fluorescent light (150 μE m−2 s−1 irradiance) in EGM medium. 11 Cells were quantified with Neubauer’s chambers and biomass was obtained via centrifugation at 4 °C after 72 h (exponential phase, -EX) and 144 h of growth (stationary phase, -ST). Biomass was washed four times with distilled water at 4 °C, and then dried by lyophilisation. A general extraction was performed in all dried samples obtained with ethanol 96° and fractionated by pH changes, and partitioned with different polarity solvents (Fig.

Furthermore, the radiolabel showed stability as predicted from the previous radiolabel stability experiment (Fig. 3), and the pertechnetate remained at the injection site bound to the NFC hydrogel. 123I-NaI was mostly distributed into the thyroid glands and stomach, in addition to being excreted to urine. 5 h post injection, no trace of 123I-NaI was found at the injection site. To explore the use of the NFC hydrogel as a drug release matrix, we selected a small drug (123I-β-CIT) and a large protein drug (99mTc-HSA) to evaluate the effect of molecule size on the rate of release from the NFC hydrogel. The in vivo release and

distribution of 123I-β-CIT and 99mTc-HSA were investigated after injecting the NFC hydrogels imbedded with the study compounds. The study compound and saline solution mixtures were used as controls (injections without the NFC hydrogel). The differences between the HSA–NFC hydrogel “implants” and saline injections

selleck kinase inhibitor were observed as 99mTc-HSA expressed a delayed release from the NFC hydrogel and 41% of the injected dose remained within the hydrogel 5 h post injection (Fig. 5a). Linear release was observed in the beginning of the study, and release AZD6244 rates calculated from the early time points (from first to 5 h) resulted in −0.0233 μg/h and −0.0139 μg/h for saline solution and hydrogel injections, respectively. Release of 99mTc-HSA was steady during the whole study. In addition, a large distribution of 99mTc-HSA was shown in the subcutaneous tissue surrounding the injection site indicating a very poor absorption of 99mTc-HSA into the circulatory system (Fig. 5b). Slight activity was detected within the bloodstream, as indicated by the radioactivity in heart and left kidney (Fig. 6). However, the distinctions between the compound itself and its metabolites cannot be made, as it is well known that 99mTc-HSA does not pass the glomerular filtration under normal renal activity. Slow absorption is probably due to the large protein size and low enzymatic activity within the subcutaneous tissue. It was shown that injections given with NFC hydrogel retained

99mTc-HSA in a smaller area within or around the hydrogel than saline solution injections (Fig. 5b), therefore 99mTc-HSA did not freely distribute into the subcutaneous tissue. This might indicate that rate of release from the hydrogel Dipeptidyl peptidase is limiting 99mTc-HSA absorption. Heart and the left kidney were selected to estimate the 99mTc-HSA absorption into the cardiovascular system. No apparent accumulation of 99mTc-HSA to any other organ was detected. No differences between the saline and hydrogel injections were observed in blood pool activity, i.e. heart (Fig. 6a). However, slight differences were detected in the left kidney of the study animals (Fig. 6b). The amount accumulated in the left kidney during the study period was low in addition to some of the activity might be due to metabolized 99mTc-HSA.

5 μl, 1 μl,

2 μl, and 4 μl) DMSO solution of 100 mM NHS-dPEG12-biotin. 100 μl of the suspension was kept for auto fluorescence reference. The cells in each tube were washed with 150 μl of PBS buffer three times, suspended in 20 μl of PBS and supplemented with 15 μl of 5 μM AV – Probe 1-Eu3+. After incubation at room temperature for 20 min, the cells were washed with 100 μl of PBS buffer and suspended in 50 μl of the same buffer. One microliter of Poly-l-lysine was spread onto a fused silica microscope substrate into an area of 0.3 cm2 and removed. One microliter of the cell suspension of labeled cells (E. coli or CHO cells) containing 109–1010 cells cm−3 in PBS buffer was spread into the same area and left to air dry for 15 min. Excitation and emission fluorescence spectra in the continuous excitation mode were recorded using QuantaMaster 1 (Photon Technology International) digital fluorometer at ambient temperature. Time-resolved MDV3100 solubility dmso and gated luminescence KPT-330 concentration measurements were performed using the previously described home-built experimental set-up [13]. A Hacker Instruments Zetopan microscope was equipped with an ICCD Camera (PI-MAX, Princeton Instruments). In the experiments, the images were taken in luminescence light using evanescent wave excitation at 351 nm as well as in scattered light using standard top illumination by xenon lamp. In the evanescent excitation, a right angle fused silica prism was illuminated

with laser light (351 nm) from a XeF laser (OPTEX, Lambda Physik). The sample was located on the hypotenuse side of the prism positioned horizontally. Images taken in scattered light from a xenon lamp were taken before and after Org 27569 the luminescent images collected in the photon counting mode. Online thresholding mode was used to discriminate photon pulses from the readout noise as well as the “cosmic events”. The 1024 × 1024 camera pixels were 8 × 8 binned resulting in 128 × 128 pixel2 images.

The microscope used an objective with the magnification of ×56 and the numerical aperture of 0.90. Combined with the intermediate “ocular” lens with the magnification of ×10 it provided the field of view of 14 × 14 μm2. In some experiments, an ×5 intermediate “ocular” lens was used resulting in the 28 × 28 μm2 field of view. The cells labeled with avidin carrying multiple probes (Probe 1-Eu3+ and Probe 4-Tb3+) were placed on the hypotenuse side of the prism mounted at the microscope base. The excitation of probes occurred in the evanescent wave by laser light totally internally reflected from the hypotenuse side inside the prism. The probes with Eu3+ have emission lifetime of ca. 0.5 ms, while the probes with Tb3+ have emission lifetime of ca. 1.5 ms. Therefore, for samples labeled with Eu3+ probes we used a gate width of 1 ms and the gate delay of 50 μs and for samples labeled with Tb3+ probes 2 ms gate width and 100 μs gate delay were used.

The work was funded by a grant to SGUL by the Bill & Melinda Gates Foundation and the Wellcome Trust, under the Grand Challenges in Global Health Initiative and by a grant to Harvard Medical School by the Bill & Melinda Gates Foundation’s Collaboration for AIDS Vaccine Discovery/Comprehensive Antibody–Vaccine Immune Monitoring Consortium, grant number 38619. We thank Professors Ralf Wagner and Hans Wolf, University of Regensburg and GENEART AG for the p97CN54-expressing plasmid and Mark Robinson and William Elsley, NIBSC for assistance. The study was integrated with efforts to standardise HIV vaccine development through the EUROPRISE Network of Excellence on Microbicides and Vaccines.

MPC

and PFM are supported by the Sir Joseph Hotung Trust. “
“In Bortezomib mw April 2009 a new influenza A/H1N1 virus strain was detected in two GDC-0068 children in Southern California, both suffering from respiratory disease [1]. Full sequence analysis showed that this new influenza strain, currently named “pandemic (H1N1) 2009” (H1N1v), is likely a reassortant between North American and Eurasian swine influenza strains [2] and [3]. Unlike most other introductions of swine influenza strains in the human population, this strain was successful in human-to-human transmission. The virus spread quickly to other countries and continents and finally, on the 11th June 2009, the WHO declared this outbreak to be a pandemic, the first one since 1968 (Hong Kong flu). On 28 April 2009, the Canadian Food Inspection Agency became involved Parvulin in the first field infection of swine with this H1N1v [4]. Introduction of the virus through an infected human was suspected, but could not be proven. On the 25th June, a second swine herd, in Argentina, was reported to the World Organization for Animal Health (OIE) as being infected [5]. Also in this case, introduction through infected humans was suspected, but could not be confirmed. In both cases the clinical symptoms in the pigs were rather mild and recovery of the pigs was

uneventful. Many more such cases in swine herds have since been detected, in countries all over the world. The susceptibility of pigs to this particular virus strain has been confirmed in several experimental studies [6], [7] and [8]. Clinical symptoms in pigs were shown to be similar to those caused by endemic swine influenza strains. It was also shown that virus transmission to susceptible pigs, at least those naïve for antibodies against any swine influenza viruses, readily occurs. Whether the H1N1v is able to outcompete endemic H1N1 and/or H1N2 strains, or whether it would be able to co-exist with these endemic strains in swine, is as yet unknown. In such cases pigs may become a reservoir from which repeated introductions into the human population could occur.

The ATA consensus emphasises the importance of comprehensive and reliable clinical pathways with clear communication. New technologies can potentially reduce the occurrence of complications and improve detection of impending life threatening postoperative emergencies, for example recurrent laryngeal nerve injury by endotracheal nerve monitoring and pre-empting of significant postoperative hypocalcaemia Doxorubicin nmr from parathyroid hormone measurement.

Postoperative haemorrhage is the critical factor determining risk acceptability for day case thyroid surgery. Whilst it is unrealistic to expect to be able to eliminate the occurrence of bleeding from the day case pathway the reduction of a significant adverse consequence may be possible with the appropriate set-up. Postoperative haemorrhage occurs between 0.9%–1.25% [3], [10], [13] and [25] and 2.1% Compound C chemical structure [11] of all thyroidectomies. The frequency of life threatening airway obstruction (due to local compression and laryngeal oedema) however is much less clear. The incidence of patients requiring tracheostomy may be a surrogate marker. Of 10, 201 thyroidectomies performed over a 40-year period at the Royal North Shore hospital 124 (1.2%) required re-operation for haemorrhage

with 31 (0.3%) requiring a tracheostomy [26]. This is comparable to Burkey’s data with a quarter requiring bedside decompression [25]. In Promberger’s series of over 30,000 thyroidectomies [24], there were 3 fatal outcomes (1 per 10,000 surgeries) and 9 of 591 (1.5%) bleeds requiring tracheostomy. Thirty-day mortality following thyroid surgery in the UK is 1 in 500 [10] and at least some of these deaths will be secondary to a postoperative haemorrhage. Incidence of fatal haematoma has not been reported in the large US studies. A postoperative thyroid bleed needs urgent assessment and at least a quarter require immediate perhaps even bedside intervention [3], [25] and [26]. Intuitively, a post-thyroidectomy haemorrhage occurring

at home would increase the mortality the risk but there is no data to prove this. In Promberger’s series, patients requiring tracheostomy had a three-fold longer interval between skin closure and recognition of symptoms/re-operation indicating that delay in diagnosis leads to laryngeal/supraglottic oedema and increased morbidity [24]. This infers that a patient bleeding at home would fare worse due to inevitable delays in intervention, but this may not necessarily be so if such bleeds were not life threatening. To assure against an increased risk from the day case setting, a reliable form of risk stratification to identify patients with a minimal bleed risk is required. Unfortunately, even with experienced clinical judgement, there is no reliable and reproducible patient and disease specific criteria to risk stratify patients for postoperative haemorrhage. A large retrospective review of 7921 thyroidectomies and 5896 parathyroidectomies over 25 years compared 21 (0.26%) and 21 (0.

Although the effects were small, the intervention is quick to apply, is maintained in situ for one week, and does not require ongoing commitment of time and effort, as do some other physiotherapy interventions (eg, exercises). Therefore, some patients may consider that the costs and inconvenience involved are small and that a combination of small reductions in pain and disability may make taping worthwhile overall. The borderline effect on lumbar flexion range of motion

is interesting. Kinesio Taping on the lower trunk increased active lower trunk flexion range of motion in healthy subjects (Yoshida and Kahanov 2007). Although various mechanisms

selleck chemical were postulated to explain this, some of which could apply in our participants, we must also consider that the mild reduction in pain could explain the greater range in our participants. The mild analgesic effect may also explain the greater performance of the trunk muscles on the McQuade test. Unfortunately, we did not record whether pain or fatigue was the limiting factor for participants during this test. Another possibility is that the presence of the taping led to greater awareness and, in turn, greater muscular activation around the area during the intervention period. This may have introduced a mild endurance training effect on the trunk musculature. The precise mechanisms underlying the effect of Kinesio

Taping on musculoskeletal pain are not yet clear. Some authors have RO4929097 hypothesised that pain is relieved by Kinesio Taping because sensory modalities operate within interconnecting, intermodal and cross-modal networks (McGlone and Reilly 2010). Others have suggested that keratinocytes of may be non-neural primary transducers of mechanical stimuli, probably via a signal transduction cascade mechanism (eg, intracellular Ca2+ fluxes) to evoke a response on adjacent C-fibres (Lumpkin and Caterina 2007). Another hypothesis is that the cutaneous stretch stimulation provided by Kinesio Taping may interfere with the transmission of mechanical and painful stimuli, delivering afferent stimuli that facilitate pain inhibitory mechanisms (gate control theory) and pain reduction (DeLeo 2006, Paolini et al 2011). A further possible mechanism by which Kinesio Taping induced these changes may be related to the neural feedback received by the participants, which may improve their ability to reduce the mechanical irritation of soft tissues when moving the lumbar spine (Kase et al 2003). Furthermore, Kase and colleagues (1996) proposed a theoretical framework to explain the decrease in lumbar pain-associated disability observed immediately after Kinesio Taping.

It has been shown previously that intranasal administration of c-di-GMP as an adjuvant for influenza vaccines can induce multifunctional influenza-specific

CD4+ Th1 cells in the spleen of immunized mice [8] and [9]. Furthermore, multifunctional Th1 cells have also been shown to be present in the blood of vaccinated human volunteers and in the non-inflamed normal VE-822 in vivo human lung tissue, as determined by their potential to produce IL-2, IFN-γ and/or TNF-α upon re-activation [31] and [32]. Consistent with the cytokine profile of influenza-specific multifunctional Th1 cells, our study showed increased IL-2 and IFN-γ levels in antigen re-stimulated PCLS of mice vaccinated with HAC1/c-di-GMP. The induction of Th1 cytokines in re-stimulated PCLS indicates that the antigen was recognized by HAC1-specific memory T-cells. These results are in line with the hypothesis by Jul-Larsen and colleagues DAPT research buy who discussed that addition of an adjuvant improves the efficacy of HAC1 toward the induction of a robust T-cell response [32]. Additionally, our results aligned with previous studies on intranasally administered c-di-GMP showing an induction of a

Th1-biased cytokine profile in re-stimulated splenocytes against target antigen [8], [9] and [33]. Yet, our study also showed a mild induction of the Th2 cytokine IL-5 and the anti-inflammatory cytokine IL-10 in re-stimulated PCLS of intratracheally c-di-GMP-vaccinated mice. The fold induction of the Th1 cytokines for the double-adjuvanted vaccinated mice, however, far exceeded the level of Th2 cytokines that were induced (IFN-γ:IL-5, about 119-fold; IFN-γ:IL-10, about 39-fold). Nevertheless, the double-adjuvanted vaccine, as well as the c-di-GMP admixed antigen, induced IL-10 secretion in PCLS upon antigenic re-stimulation which exceeded the non-stimulated IL-10 baseline level. Among other cytokines, IL-10 can be released 3-mercaptopyruvate sulfurtransferase by influenza-specific

CD4+ memory T-cells and has been described as having a putatively crucial role in regulating inflammation during acute influenza infection [34]. The fact that the double-adjuvanted vaccine induced IL-10-competent cells might also contribute to a reduced level of inflammation in the lungs with repeated exposure to the virus post vaccination. Overall, the data presented in the current study demonstrate that the double-adjuvanted HAC1 vaccine is immunogenic in the mouse model when administered intratracheally. Even though the protective efficacy of the double-adjuvanted HAC1 vaccine needs to be evaluated in a relevant animal model, the present study demonstrates that the double-adjuvanted HAC1 induces systemic functional antibody response as well as local humoral and cellular immune responses when administered via the respiratory tract, indicating potential for future needle-free vaccine applications. The authors would like to thank Olaf Macke, Sabine Schild, Sarah Dunker and Olga Danov for their technical assistance. The authors would like to thank Dr.