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International cohort study of 73 anti-Ku-positive patients: association of p70/p80 anti-Ku antibodies with joint/bone features and differentiation of disease populations by using principal-components analysis
Katja Lakota1,
Gerhard G Thallinger2,
Snezna Sodin-Semrl1,
Blaz Rozman1,
Ales Ambrozic1,
Matija Tomsic1,
Sonja Praprotnik1,
Sasa Cucnik1,
Katjusa Mrak-Poljsak1,
Angela Ceribelli3,
Ilaria Cavazzana3,
Franco Franceschini3,
Jiri Vencovsky4,
Laszlo Czirják5,
Cecilia Varjú5,
Gunther Steiner6,
Martin Aringer6,
Bojana Stamenkovic7,
Oliver Distler8,
Marco Matucci-Cerinic8 &
Tanja Kveder1
An international cohort study of 73 anti-Ku-positive patients with different connective tissue diseases was conducted to differentiate the anti-Ku-positive populations of patients based on their autoantibody profile and clinical signs/symptoms and to establish possible correlations between antibodies against Ku p70 and Ku p80 with autoimmune diseases.
Sera of anti-Ku-positive patients were collected from six European centers and were all secondarily tested (in the reference center); 73 were confirmed as positive. Anti-Ku antibodies were detected with counter-immunoelectrophoresis (CIE), line immunoassay (LIA), and immunoblot analyses. All clinical and laboratory data were follow-up cumulative data, except for anti-Ku antibodies. Statistical analyses were performed by using R (V 2.12.1). The Fisher Exact test was used to evaluate the association between anti-Ku antibodies and diagnosis, gender, clinical signs, and other observed antibodies. The P values were adjusted for multiple testing. Separation of disease populations based on the presence of antibodies and clinical signs was investigated by principal-components analysis, which was performed by using thr// R's prcomp function with standard parameters.
A 16% higher prevalence of anti-Ku p70 was found over anti-Ku p80 antibodies. In 41 (57%) patients, a combination of both was detected. Five (7%) patients, who were CIE and/or LIA anti-Ku positive, were negative for both subsets, as detected with the immunoblot; 31% of the patients had undifferentiated connective tissue disease (UCTD); 29% had systemic sclerosis (SSc); 18% had systemic lupus erythematosus (SLE); 11% had rheumatoid arthritis; 7% had polymyositis; and 3% had Sjögren syndrome.
A significant positive association was found between female patients with anti-Ku p70 and joint/bone features, and a significant negative association was found between female patients with anti-Ku p80 only and joint/bone features (P = 0.05, respectively). By using the first and the third components of the principal-component analysis (PCA) with 29 parameters evaluated, we observed that the anti-Ku-positive population of UCTD patients had overlapping parameters, especially with SLE, as opposed to SSc, which could be helpful in delineating UCTD patients.
The Ku complex is a heterodimer made of p70 and p80 subunits that play major roles in DNA repair, transcriptional regulation, and replication and have also been involved in telomere maintenance, V(D)J recombination, and development of the brain. Ku is ubiquitously found in the nucleus; however, it has also been localized in the cytoplasm, as well as on cellular surfaces [1–3]. In humans, Ku p70 and Ku p80 genes are localized on different chromosomes (22q13 and 2q33, respectively). Their proteins share sequence homologies, as well as display marked structural homologies. Ku p70 and Ku p80 are generally believed to form and function as a heterodimer, but each also has its own unique activities. Whereas p70 resembles a transcriptional activator, and its DNA-binding domain has been localized to its C-terminus, p80 does not seem to bind DNA and may be involved in interactions with other proteins [4]. The differences also extend to knockout mice models. Ku70-knockout mice showed deficiencies in subgroups of mature T lymphocytes and a significant incidence of thymic lymphoma, whereas Ku p80-knockout mice had arrested T-and B-cell development at early stages and caused growth retardation [5, 6].
Although antibodies against Ku antigen (anti-Ku) were originally described in patients with scleroderma-polymyositis overlap syndrome, reports showed that anti-Ku antibodies are found also in many diseases, in particular, in patients with systemic lupus erythematosus (SLE), systemic sclerosis (SSc), and undifferentiated connective tissue disease (UCTD) [7]. The prevalence of anti-Ku antibodies has recently been evaluated in a European EUSTAR-initiated multicenter case-controlled study with 625 SSc patients in whom a clinically distinct subset resulted in 14 anti-Ku-positive patients (2.2%) [8]. The presence of anti-Ku antibodies in the study of Rozman et al. [8] was reported to be associated with synovitis, joint contractures, and clinical features of myositis, and negatively associated with vascular manifestation of disease. Cavazzana et al. [7] retrospectively analyzed the prevalence and clinical signs of anti-Ku antibodies in patients affected by different autoimmune diseases. Most of anti-Ku-positive patients were found to be affected by UCTD and overlap syndromes, including polymyositis, SSc, and SLE. Interstitial lung disease, myositis, articular symptoms, Raynaud phenomenon, and sicca syndrome represented the main clinical features detected in this cohort. Both recent studies give a broad overview of anti-Ku antibodies and clinical, serologic, and diagnostic correlations.
In 1989, Reeves et al. [9] reported on levels of antibodies against Ku p70 and Ku p80 longitudinally over a period of 70 months in sera of patients with SLE (n = 2), mixed connective tissue disease (n = 1), and Sjögren syndrome (n = 1). Their study suggested that anti-Ku p70/anti-Ku p80 antibodies are generated by a selective antigen-driven mechanism; however, polyclonal activation also frequently accompanied autoantibody production. Human Ku autoantibodies are thought to react with at least eight different epitopes of the human complex [10]. SLE sera reacted on immunoblots with at least three epitopes of p70 (aa 560-609, 506-535, and 115-467), and three epitopes of p80 (aa 682-732, 558-681, and 1-374); one strong antigenic region (immunodominant epitope of p70) was revealed near the C-termini of p70 (conformational or discontinuous epitope) and p80 [11].
Yaneva and Arnett [12] examined anti-Ku p70/anti-Ku p80 antibodies with quantitative immunoblotting and found that all positive sera (from mixed ethnic patients with SLE (n = 13), SSc (n = 9), myositis (n = 2), and Sjögren syndrome (n = 2)) had antibodies against Ku p80, and only one serum (from a dermatomyositis patient) did not react with Ku p70. Only anti-Sm antibodies appeared to be associated with anti-Ku antibodies.
The aim of our study was to examine whether disease populations, with special emphasis on UCTD, could be depicted based on their associated clinical and laboratory data by using principal-component analysis (PCA). Further, we aimed to investigate the association of anti-p70 and/or anti-p80 antibodies with the presence of clinical signs, autoimmune diseases, and their respective autoantibodies. Therefore, we evaluated the largest European cohort study to date with 73 anti-Ku-positive patients.
Sera of anti-Ku-positive patients were collected from six European centers (Ljubljana, Brescia, Pécs, Prague, Nis, and Vienna) and were all secondarily tested; 73 were confirmed as positive in Ljubljana. Among them were 61 female and 12 male subjects. Their mean age was 57.8 years, ranging from 16 to 86 years. Anti-Ku positivity was determined with counter-immunoelectrophoresis (CIE)/line immunoassay (LIA) in the Immunological Laboratory of the Department of Rheumatology, University Medical Center, Ljubljana. Among these, only one patient was LIA but not CIE positive. The diagnoses of SSc, SLE, rheumatoid arthritis, polymyositis, and Sjögren syndrome were defined in the participating centers according to well-established criteria [13–17]. The criteria for UCTD were used, as suggested by Distler et al. [18] because this disease has no uniformly accepted diagnostic criteria. The overlaps were gathered under the diagnosis, which represented the leading clinical symptoms and signs of the disease.
Because of the large amount of clinical and laboratory data, besides some single clinical and laboratory features, a more simplified version of presenting the compilation of data was used.
SLE skin" is defined by the presence of one or more of the following: malar rash, discoid rash, photosensitivity
Joint and bone" is defined by the presence of one or more of the following: Joint features were evaluated clinically (synovitis and joint contractions) and by radiographic examination (erosive arthritis, acro-osteolysis)
Muscle" is defined by the presence of one or more of the following: weakness or atrophy of muscles, serum CK elevation, EMG, and muscle biopsy in line with the appropriate criteria for inflammatory myopathy
Neurology" is defined by the presence of one or more of the following: seizures, psychosis, or peripheral neuropathy
Gastrointestinal" is defined by the presence of one or more of the following: dysphagia, gastroesophageal reflux, or early satiety
Pulmonary" is defined by the presence of one or more of the following: dyspnea, NYHA I/II, fibrosis (plain radiograph), restrictive defect, or pleuritis
Heart" is defined by the presence of one or more of the following: palpitations, conduction blocks, or abnormal diastolic function
Renal" is defined by the presence of one or more of the following: proteinuria (more than 0.5 g/day), renal insufficiency, or renal crisis
Antiphospholipid antibodies" are defined by the presence of one or more of the following: anticardiolipin antibodies, or anti-β2-glycoprotein antibodies, lupus anticoagulant, detected at least on two occasions, as defined by APS criteria [19]
Cytopenia" means a low number of leukocytes and/or erythrocytes and/or thrombocytes
All clinical and laboratory data are follow-up cumulative data, except for anti-Ku antibodies, as determined with CIE/LIA and anti-p70/anti-p80 immunoblot detection. Informed consent was obtained, and the study was approved by the Ethics Committee of the Slovenian Ministry of Health.
Stored sera were sent on dry ice to the reference center (Department of Rheumatology, Ljubljana), where they were tested. Antibodies against soluble nuclear antigens (anti-ENA): Ro/SS-A, La/SS-B, Sm, U1RNP, PCNA, SL, Scl-70, PM/Scl, Jo-1, and Ku were screened with CIE, as described [20], which show conformational epitopes and are not able to discriminate between anti-Ku p70 and/or anti-Ku p80.
Sera from the aforementioned centers were additionally tested in the same reference center for antinuclear antibodies (ANAs) with indirect immunofluorescence on HEp-2 cell-line substrate (Immunoconcepts, Sacramento, CA, USA) and with LIA for autoantibodies present in myositis, which detects, besides anti-Ku, also antibodies against Jo-1, Mi-2, PM/Scl, and U1-snRNP (Imtec-Myositis-LIA; Imtec, Immunodiagnostika, Berlin, Germany). The Ku antigen on Imtec-Myositis-LIA is a human recombinant Ku p70/p80, which also does not distinguish between the two subunits. Hep-2 patterns were detected with indirect immunofluorescence, rheumatoid factor, with latex fixation test and Waaler Rose reaction, anti-cyclic citrullinated protein antibodies with enzyme-linked immunosorbent assay (ELISA; Immunoscan CCPlus, Euro-Diagnostica AB, Malmö, Sweden), aPL with an in-house ELISA (for anti-aCL IgG and IgM isotypes and for anti-β2-GPI, IgG, IgM, and IgA have been measured) and anti-dsDNA antibodies with an in-house FARR-RIA assay.
To detect anti-p70 and anti-p80 antibodies, immunoblotting was used. Nuclear extracts were prepared from THP-1 (human acute monocytic leukemia cell line). Centrifuged THP-1s were washed with PBS, and protease inhibitors (Halt Protease Inhibitor Cocktail Kit; Pierce, Rockford, IL, USA) were added. Extraction was done according to instructions (NE-PER Nuclear and Cytoplasmic Extraction Reagents; Pierce), and protein concentration in nuclear extract was measured with the Bio-Rad Protein Assay (Bio Rad, Munich, Germany). The immunoblot method included an initial immunoprecipitation step, which was performed with Protein A/G PLUS-Agarose Immunoprecipitation Reagent; Santa Cruz, Santa Cruz, CA, USA): 500 μg of proteins from the nuclear extract was mixed with 2 μg mouse monoclonal antibody Ku-3 (clone 162) (NeoMarkers, Fremont, CA) and incubated 2 hours at 4°C. Then 20 μl of resuspended A/G Agarose was added, and the mixture was incubated another 2 hours at 4°C. Washing of pellet was done with PBS for 4 times, each time followed by centrifugation. After the final wash, pellets were resuspended in PBS and electrophoresis SDS-sample buffer and boiled for 3 minutes for protein elution. Sample volume corresponding to 50 μg of primary nuclear extract/cm of gel length was analyzed on 10% SDS-polyacrylamide gels in Tris/glycine buffer in BioRad Mini Protean apparatus and transferred to nitrocellulose (BA 85; Schleicher & Schuell, Munich, Germany) at 100 V, 250 mA for 45 minutes. The dry membrane was blocked with TBS/0.05% Tween buffer with 5% milk. Patient sera were diluted 1:50 and incubated 2 hours, followed by washing and 40 minutes of goat anti-human IgG-HRP (1:1,000) (BioRad) incubation. Detection was done with luminol (Western Blotting Luminol Reagent, Santa Cruz, CA, USA) in G:box (Syngene, Cambridge, UK) with chemiluminescence. As positive controls, monoclonal goat antibodies (Ku-86 (C-20), Santa Cruz; Ku-70 (C-19), Santa Cruz, diluted 1:500) and donkey anti-goat IgG-HRP conjugate (diluted 1:1,000, Santa Cruz) were used. All samples were tested also for colorimetric determination, and the secondary antibodies used were rabbit anti-human alkaline phosphatase (Bio Rad) followed by the substrate NBT/BCIP (Pierce).
Statistical analyses were performed by using R (V 2.12.1) [21]. The Fisher Exact test was used to evaluate the association between anti-Ku antibodies and diagnosis, gender, clinical signs, and other observed antibodies. The P values were adjusted for multiple testing by using the approach of Benjamini and Hochberg [22]. An adjusted P value below or equal to 0.05 was considered statistically significant. Separation of disease populations based on the presence of antibodies and clinical signs were investigated with PCA. PCA was performed by using the R prcomp function with standard parameters. PCA allows the identification of latent variables (principal components) in the data based on observed variables (in our case, 29 parameters, the presence of those autoantibodies and clinical signs that show five or more observations).
Anti-Ku p70/80 prevalence
Within our anti-Ku-positive population (n = 73), 60 (83%) anti-Ku p70-positive patients were found, whereas 48 (67%) patients were anti-Ku p80 positive. This represents a 16% higher prevalence of anti-Ku p70 over anti-Ku p80. For one UCTD patient, the immunoblot p70/p80 differentiation was not able to be performed. Nineteen (26%) patients had only anti-Ku p70, whereas seven (10%) patients had only anti-Ku p80 antibodies detected (Table 1). In 41 (57%) patients, a combination of both anti-p70/anti-p80 antibodies was seen. Only five (7%) patients who were CIE anti-Ku positive were negative for both subsets of antibodies in the immunoblot (Table 1). Twenty anti-Ku-negative controls (blood donors) were tested only in the immunoblots and did not show any reactivity (data not shown).
Table 1 Prevalence of anti-Ku p70/p80 in patient groups as detected with immunoblot analysis
Anti-Ku p70/80 association with clinical signs, symptoms, and diagnosis
We next analyzed associations with clinical symptoms and presentations. An overview of associations between anti-Ku-positive patients, as determined by CIE/LIA, with clinical signs and symptoms is given in Figure 1. When looking specifically at anti-Ku p70 and/or anti-Ku p80, a significantly positive association between anti-Ku p70 antibodies was exclusively found with joint/bone features (synovitis, erosive arthritis, joint contractures, and acro-osteolysis) (P = 0.05), whereas a significant negative correlation was found between anti-Ku p80 antibodies only and joint/bone features, even after adjustment of the P value for multiple testing. Both findings were in female patients. No significant associations were found between the presence of anti-Ku p70 and/or anti-Ku p80 antibodies and any of the diagnoses, even when sex or age-related associations were considered.
The number of total patients is 73, except for the columns with not determined (ND) samples. For a detailed overview of the clinical signs and symptoms, please refer to the Materials and methods Subjects section. ND, the data are not available because of missing procedures necessary to define the particular parameter.
Anti-Ku p70/80 association with other autoantibodies
A summary of the percentage of anti-Ku-positive patients, as determined by CIE/LIA to all autoantibodies measured in this study, is shown in Figure 2. A single anti-Ku positive (positive for both anti-Ku p70 and anti-Ku p80 antibodies) anti-centromere antibodies (ACA)-positive case was found, and this patient was clinically diagnosed as having SLE/Sjögren syndrome. All but one anti-Ku-positive patients were ANA positive, showing mostly a speckled or a speckled plus nucleolar immunofluorescence pattern in all groups.
The total number of patients is 73, except for the columns with not determined (ND) samples. ACAs, anticentromere antibodies; ANAs, antinuclear antibodies; anti-CCPs, antibodies to cyclic citrullinated peptide; anti-SL (sicca/lupus), anti-Scl-70 (DNA topoisomerase I), anti-dsDNA, antibodies against double stranded DNA; aPLs, antiphospholipid antibodies; ND, data are not available, because of missing procedures necessary to define the particular parameter; PCNA, proliferating cell nuclear antigen; RF, rheumatoid factor; UDA-HSE and UDA-RTE, undefined antibodies as detected with CIE by using human spleen and rabbit thymus, respectively, as sources of antigens.
No significant associations were found between the presence of anti-Ku p70 and/or anti-Ku p80 antibodies and any autoantibodies, when sex- or age-related associations were considered. However, before adjustment of the P value, a significant positive association was found between antiphospholipid antibodies and anti-Ku p80 antibodies only, in both the overall and female populations.
Patient stratification based on presence of clinical signs and antibodies
To investigate whether it is possible to stratify the patients diagnosed with SLE, UCTD, and SSc based on their autoantibody status and clinical signs/symptoms, we used PCA (Figure 3). The principal components (PCs) are ordered according to the amount of variance in the data they explain, with PC1 being the most informative.
Principal-component analysis of the presence of 10 antibodies and 19 clinical signs for 57 patients diagnosed with SSc, SLE, or UCTD. The plot is based on principal components 1 and 3, which explain 18.96% and 8.74% of the total variance of the data, respectively. The individual disease populations are circumscribed by an ellipse representing an 87% confidence level.
By using PC1 and PC3 for the PCA, we observed that the anti-Ku-positive SLE and SSc populations had little overlap, whereas the anti-Ku-positive UCTD patients in our cohort had a greater overlap with anti-Ku-positive SLE patients than with anti-Ku-positive SSc patients.
A significant association was recently demonstrated between the presence of anti-Ku antibodies and musculoskeletal features in SSc [8]. The current study focuses on the differences between the clinical presentation of anti-Ku p70- and anti-Ku p80-positive patients, regardless of their diagnoses. The study included six European centers, all known for their expertise in the field of systemic autoimmune diseases. With a total of 73 patients, this cohort is the largest to date and showed an overall 16% higher prevalence of antibodies detected against the Ku p70 subunit as compared with Ku p80, which is a novel finding. These data differ from those of a study by Wang et al. [23], in which they showed a 28% higher prevalence of autoantibodies against p80 on a total of 58 systemic autoimmune patients; however, this population was examined in the United States and presumably differs from our European cohort. Additionally, the anti-Ku antibodies were detected with ELISA or immunoprecipitation by using K562 cell Ku antigen, and the clinical diagnoses and disease definitions differed from those used in our study, which could have also influenced the results. The same report also indicates the presence of stabilizing autoantibodies (in terms of stabilizing intermolecular contacts between the p70 and p80 Ku subunits) against both recombinant antigens. In the current study, UCTD and SSc patients were the most prevalent in the anti-Ku-positive group, whereas in the Wang et al. [21] study, SLE and mixed connective tissue disease overlap patients were highest in number.
Epitope mapping has identified at least eight autoepitopes on the Ku antigen, located on p70, p80, or both subunits, suggesting strongly that an antigenic conformational epitope exists on the C-terminus of p70 and p80 [11]. In our case, five of the patients (7%) who were anti-Ku positive by CIE/LIA were negative for both subsets of antibodies in the immunoblot assay and could be implied to recognize a conformational epitope.
No significant association was found between anti-Ku p70 and/or anti-Ku p80 and any of the diagnoses, even when looking for sex- and/or age-related associations. However, a significant positive correlation (P = 0.05) was found between anti-Ku p70 and joint/bone features, and a significantly negative correlation was shown between anti-Ku p80 and joint/bone features (in the female population of anti-Ku-positive patients, representing 84% of the overall population). The correlation is evidently not strong; however, looking at the typical inflammatory joint disease, such as RA, it is worth mentioning the main characteristics of our eight RA patients showing relatively mild joint affliction. The disease activity (by ESR and CRP) was (looking longitudinally) described as high in two patients, medium in two patients, and low in the rest. The radiographic examination of the diseased joints was reported as highly destructive with deformations in one patient and rather mild with slight narrowing of the joint space and few erosions in the rest. The immunoserology showed five seropositive patients (RF-latex and Waaler Rose test and/or anti-CCP-ELISA) and three seronegative patients for both. Furthermore, they typically had high titers of anti-nuclear antibodies. As expected, four patients had anti-Ro, and two patients had anti-La antibodies.
These results might provide the basis for further studies of anti-Ku-related pathogenesis, particularly with respect to joint/bone features. Of interest, Ku p70-knockout mice have increased rates of primary mouse ear fibroblast transformation [24], and embryonic fibroblasts from Ku 80-knockout mice have a prolonged G2 phase after H2O2 treatment [5, 25]. It would be interesting to determine the specific roles of the antigens Ku p70/p80 in synovial fibroblasts, especially in DNA-dependent protein kinase catalytic subunit independent processes.
The compilation of specific clinical signs/symptoms and the diagnoses-related prevalence of certain organs/tissues being affected could have introduced a certain bias in the analyses, because of this targeted approach, as described in Materials and Methods. Also, patient diagnoses and clinical signs coming from many different centers and evaluated by different clinicians could result in variations of interpretation, and we do not exclude some possible bias arising from this. However, the representatives from each center were instructed to reevaluate the clinical charts of all patients included. Concerning the CIE/LIA anti-Ku-positive group, the lack of ACA (which had been previously shown [8]) was now confirmed in our larger anti-Ku-positive SSc group. Just one anti-Ku-positive case (with antibodies against both subunits) was ACA positive and diagnosed as having SLE/Sjögren syndrome.
To compare UCTD with SLE and SSc, and to understand the complexity of clinical features in systemic autoimmune diseases, we stratified anti-Ku-positive patients by using PCA. The analysis showed a clear differentiation of anti-Ku-positive SLE and SSc patients, whereas anti-Ku-positive UCTD patients were positioned in between, with a tendency for greater overlap of UCTD with SLE than with SSc. In our Caucasian population of patients, this could imply that the detection of anti-Ku antibodies might help in stratifying UCTD.
In conclusion, anti-Ku p70/p80 antibodies are not representative markers of a single systemic autoimmune disease. In our study, we showed a higher prevalence of antibodies against Ku p70 as compared with anti-Ku p80. PCA analysis showed that anti-Ku-positive UCTD patients in our cohort had a greater overlap with anti-Ku-positive SLE patients than with SSc patients. Therefore the finding of anti-Ku positivity in UCTD patients might indicate the progression to SLE.
Anti-Ku p70 was positively and anti-Ku p80 was negatively associated (even after adjustment of the P value) with joint/bone features, irrespective of diagnosis within connective tissue diseases, which could be an indication of the p70 Ku antigen potential speculative protective role in joint pathophysiology.
ACAs:
anticentromere antibodies
ANAs:
antinuclear antibodies
anti-CCPs:
antibodies to cyclic citrullinated peptide
anti-dsDNAs:
antibodies against double-stranded DNA
aPLs:
antiphospholipid antibodies; anti-Scl-70 (DNA topoisomerase I); anti-SL (sicca/lupus)
PCNA:
proliferating cell nuclear antigen
PM/DM:
polymyositis/dermatomyositis
SLE:
SS:
SSc:
UCTD:
undifferentiated connective tissue disease
UDA-HSE and UDA-RTE:
undefined antibodies as detected with CIE by using human spleen and rabbit thymus: respectively: as sources of antigens.
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Support for this study was obtained from the Ministry of High Education, Science and Technology of Slovenia by grant P3 0314 and the Austrian Ministry of Science (GEN-AU project BIN to GGT). JV obtained support MSM 0021620812 from the Ministry of Education, Youth and Sports of the Czech Republic.
Department of Rheumatology, University Medical Centre, Ljubljana, Slovenia
Katja Lakota, Snezna Sodin-Semrl, Blaz Rozman, Ales Ambrozic, Matija Tomsic, Sonja Praprotnik, Sasa Cucnik, Katjusa Mrak-Poljsak & Tanja Kveder
Institute for Genomics and Bioinformatics, Graz University of Technology, Graz, Austria
Gerhard G Thallinger
Rheumatology & Clinical Immunology Unit, Spedali Civili, Brescia, Italy
Angela Ceribelli, Ilaria Cavazzana & Franco Franceschini
Institute of Rheumatology, Prague, Czech Republic
Jiri Vencovsky
Department of Immunology and Rheumatology, Medical School, University of Pécs, Pécs, Hungary
Laszlo Czirják & Cecilia Varjú
Department of Rheumatology, Internal Medicine III, Medical University of Vienna, Vienna, Austria
Gunther Steiner & Martin Aringer
Department for Rheumatology, Institute for Treatment and Rehabilitation of Rheumatic and Cardiovascular diseases, Niska Banja, Serbia
Bojana Stamenkovic
Department of BioMedicine, Division of Rheumatology AOUC, Denothe Center, University of Florence, Florence, Italy
Oliver Distler & Marco Matucci-Cerinic
Katja Lakota
Snezna Sodin-Semrl
Blaz Rozman
Ales Ambrozic
Matija Tomsic
Sonja Praprotnik
Sasa Cucnik
Katjusa Mrak-Poljsak
Angela Ceribelli
Ilaria Cavazzana
Franco Franceschini
Laszlo Czirják
Cecilia Varjú
Gunther Steiner
Martin Aringer
Oliver Distler
Marco Matucci-Cerinic
Tanja Kveder
Correspondence to Snezna Sodin-Semrl.
KL was involved in manuscript writing, data generation (immunoblot assays and compilation of the data in table form), and data analysis. GGT performed the statistical analysis, including the principal-component analysis, and was involved in critical data interpretation and manuscript editing. SS-S was involved in study planning and design, interpretation of results, and manuscript writing/editing. BR was in charge of the overall clinical data, their interpretation, and critical review. SC took part in the autoantibody measurements, interpretation of the results, and manuscript writing. KM-P was involved in immunoassays and manuscript drafting. AA, MT, SP, AC, IC, FF, JV, LC, CV, GS, MA, BS, OD, and MM-C all contributed sera samples, clinical data from their centers, and critical manuscript editing and review. TK provided mentorship and was involved in planning of the study and manuscript editing. All authors read and approved the final manuscript.
Katja Lakota, Gerhard G Thallinger contributed equally to this work.
Lakota, K., Thallinger, G.G., Sodin-Semrl, S. et al. International cohort study of 73 anti-Ku-positive patients: association of p70/p80 anti-Ku antibodies with joint/bone features and differentiation of disease populations by using principal-components analysis. Arthritis Res Ther 14, R2 (2012). https://doi.org/10.1186/ar3550
Systemic Lupus Erythematosus Patient
Mixed Connective Tissue Disease


For those of us on New Years resolutions, there are several Weight Watchers Recipe Books available right now to download to your Kindle.
If you don't have a Kindle, remember you can read these books on your computer or other mobile devices.
There are a number of other books that are free for prime members only.


text:
Shantell Martin (1 de octubre de 1980) es una artista visual británica conocida por sus dibujos de flujo de consciencia y proyecciones de luz. Vive y trabaja en Nueva York pero participa en proyectos comerciales, privados y públicos a nivel internacional.

Años tempranos
Shantell Martin nació en Londres del Este y estudió en Bexleyheath School al sureste Londres. Después de cursar un año en Camberwell College of Arts, también al sureste Londres, Reino Unido (1991-1999), Martin fue admitida a Central Saint Martin's College of Art and Design en Londres, Inglaterra. Se graduó con honores en 2003.

Ha dibujado desde que era una niña y vivía en el complejo de viviendas públicas Thamesmead en Londres. Como no la dejaban dibujar en las paredes,  tomaba un bolígrafo y dibujaba personajes debajo de su cama y dentro de las cortinas en su dormitorio. Fue entonces cuando desarrolló las figuras de línea que aparecen en su trabajo hasta el día de hoy. " Hay dos tipos de hombres de palo, los que jalan y empujan y mantienen el trabajo junto," dice Martin, "y los hombres de palo que juegan y son perezosos. Es para recordarnos que tenemos que trabajar y tenemos que divertirnos."

Siendo la única niña de raza mixta dentro de una familia de rubios con ojos azules, siempre se sintió diferente. Quizás es por eso que desde una edad temprana, Martin se ha hecho la misma pregunta: ¿Quién eres? La angustia existencial la siguió a Central Saint Martins, donde  estudió diseño gráfico. Fue una época en la que se describe como una estudiante universitaria enojada y confundida. "El crecer en un entorno de gente blanca de clase media sin sentirte en control de tu futuro, del ambiente o de tu potencial, puede ser frustrante" comenta Martin. Para expresarse, la artista desarrolló un personaje llamado Hangman (Verdugo). "Es un personaje con forma de robot que pintaba en todas partes Londres,"  explica. "El verdugo era un hombre de negocios en su vida anterior y decidió cortar la horca—el ambiente casero, el sistema de clase, el prejuicio y las expectativas bajas de las personas."

Después de su graduación vivió en Japón donde primero experimentó con el performance. De 2006 a 2009, Martin desarrolló sus habilidades de dibujo a través de "Liveography"—el proceso de proyectar dibujos en vivo con acompañamiento de sonido, música u otra experiencia. Participó en conciertos de música, festivales de diseño y en espacios públicos de manera internacional. También creó una serie de dibujos micro detallados en una serie de 27 libretas que más tarde se convertirían en el tema de un libro.

Trabajo actual
En 2009 Martin se mudó a Nueva York. Este periodo marcó la próxima fase de su carrera donde comenzó a enfocarse principalmente en dibujo físico. En Nueva York, Martin continuó enfocándose en varios proyectos personales, comerciales y colaborativos. Ha experimentado con diferentes técnicas y medios, incluyendo textiles, cerámica, circuitos electrónicos y el bordado. El trabajo actual de Martin explora temas de transparencia, identidad y experiencia.

Su primera exposición individual Continuous Line (Línea Continua), se llevó a cabo en Black and White Gallery en Brooklyn, Nueva York, y su primera exposición en un museo titulada ARE YOU YOU ocurrió en el Museum of the Contemporary African Diaspora (Museo de la Diáspora Africana Contemporánea) en Brooklyn. A esto le siguió Black and White (Negro y Blanco), una colaboración en bordado con su abuela que se presentó como parte de la exposición colectiva Crossing Brooklyn que se presentó en el Museo de Brooklyn del 3 octubre al 4 de enero de 2015.

Además de su producción artística, Martin es una figura pública. En 2012, su obra y dormitorio en Bed-Stuy fueron incluidos en la sección Casa y Jardín del New York Times.  Su estilo personal ha sido documentado en la revista Vogue, y New Yorker Magazine creó un video corto sobre su proceso creativo en 2014, llamado Follow the Pen (Sigue el Bolígrafo).

Exposiciones
The Rise of Sneaker Culture, Exposición Colectiva, Brooklyn Museum (Nueva York) (10 de julio - 4 de octubre de 2015)

New Idols, Exposición colectiva, Studio 301  (Nueva York) (5 de septiembre - 5 de octubre de 2015)

Crossing Brooklyn, exposición colectiva, Brooklyn Museum (Nueva York) (3 de octubre - 4 de enero de 2015)

Are You You, Museum of the Contemporary African Diaspora (Nueva York) (26 de abril - 27 de julio de 2014)

Instalación exterior, Out of the Box: The Rise of Sneaker Culture, Bata Shoe Museum, (Toronto) (mayo de 2013 - junio de 2014)

Continuous Line, exposición individual, Black and White Gallery, Brooklyn Nueva York (21 de septiembre @– 28 de octubre de 2012)

Mix Tape en Milk Gallery (Nueva York) (15 de junio de 2012)

Message in a Bottle, exposición individual en World Six (Florida) (2011)

Signal to Noise (performance en vivo), Museum of the Moving Image (Nueva York) (15 de enero de 2011)

Residencies y otras posiciones
Profesora Adjunta en ITP, Tisch School of the Arts de la Universidad de Nueva York (2013@–presente)

Académica visitante en el grupo de Informática Social del Laboratorio de Medios de Comunicación del Massachusetts Institute of Technology (2014–presente)

Miembro de consejo consultivo, Climate Museum (2015)

Artista Residente de P3 Studio, Cosmopolitan Hotel en Las Vega, NV (14 de septiembre - 10 de octubre de 2015)

Artista Residente en Summit Series (16 al 18 de abril de 2015)

Artista de la Nueva Frontera, Sundance Institute (2014)

Embajadora, Proyecto de Pobreza Global (2013)

Artista Residente en Clark College (Vancouver, Washington) (26 de abril - 6 de mayo de 2013)

Referencias

Dibujantes del Reino Unido
Personas vivas
Nacidos en Londres

redpajama_set_name: RedPajamaWikipedia


text:
package ru.job4j.jmm;

import org.junit.Test;

/**
 * Рассмотрение проблемы видимости общих ресурсов для потоков.
 */
public class VisibilityProblemTest {
	/**
	 * Рассмотрение проблемы видимости общих ресурсов для потоков.
	 */
	@Test
	public void test() {
		SharedObject sharedObject = new SharedObject();
		Thread writerThread = new WriterThread(sharedObject);
		Thread readerThread1 = new ReaderThread(sharedObject);
		Thread readerThread2 = new ReaderThread(sharedObject);
		writerThread.start();
		readerThread1.start();
		readerThread2.start();
		try {
			writerThread.join();
			readerThread1.join();
			readerThread2.join();
		} catch (InterruptedException e) {
			e.printStackTrace();
		}
	}
}

redpajama_set_name: RedPajamaGithub


The main 2017-18 Upper Deck Series 2 Hockey set adds another 250 cards.
The first 200 are veterans while the final 50 are Young Guns Rookie Cards.
Inserted 1:4 packs, each hobby box has six Young Guns. The checklist includes second overall pick in the 2017 draft, Nolan Patrick. It's normal for Upper Deck to balance out some of the top rookies each year when it comes to the popular subset.
2017-18 Upper Deck Series 2 Hockey has some familiar parallels. The acetate Clear Cut cards return as hobby exclusives. Veterans (#251-450) are 1:90 packs. Young Guns land 1:360.
Serial-numbered parallels include Exclusives (/100) and High Gloss (/10). Printing Plates are also randomly inserted in packs.
UD Portraits has 50 top rookies at 1:6 packs. Additionally, these can be found in Gold (#/99) and Platinum Blue (#/25) parallels. Also for the first-year players, the die-cut Rookie Breakouts (#/100) set utilizes acetate card stock.
Find clear cut PETG Parallels of the complete Series 2 Base Set, falling approximately 1 in 3 boxes featuring all the 50 young guns.
Collect the entire UD Portraits Rookie Set, featuring 50 Top-Tier Rookies, Hitting 4 Per Hobby Box.
Look for UD Canvas Young Guns, Falling 1 in 48 Packs.


text:
Advanced Tuning
SQL Tuning
Perform Tuning
Tuning Instance
Data Structures «Prev Next»
Data Blocks
Oracle Segment Header Internals
PCtfree Optimal Performance
PCtused Optimal Performance
Water Mark Active
Object Oriented Database
Abstract Data Types
Oracle Data Dictionary
Sending DBA Alert Output
Partitioned Tuning
DBA Tab Partitions View
Partitioned Index Maintenance
Data Base Objects
DBA Partition Views
Index Techniques
Star Query Process
Function Based Indexes
Bitmap Indexes
Using Concatenated Indexes
Oracle Database Tuning
Oracle Tuning - Glossary
Introduction to Tuning with Oracle Data Structures and Advanced Tuning Concepts
This module deals with the new data type structures and explains their performance implications for Oracle databases. Prior to the introduction of Oracle, critics were comparing the added functionality of the new object-oriented databases with the traditional relational database model.
With Oracle we see several new object-oriented data structures that promise faster performance. In this module, we will take a closer look at these new features. The next lesson reviews the new Oracle data structures.
Oracle includes numerous data structures to improve the speed of Oracle SQL queries. Taking advantage of the low cost of disk storage, Oracle includes indexing algorithms that dramatically increase the speed with which Oracle queries are serviced. This module explores the internals of Oracle indexing and reviews the standard
b-tree index,
bitmap indexes,
function-based indexes, and
index-only tables (IOTs); and
demonstrates how these indexes may dramatically increase the speed of Oracle SQL queries.
Oracle uses indexes to avoid the need for large-table, full-table scans and disk sorts, which are required when the SQL optimizer cannot find an efficient way to service the SQL query.
Module Objectives
By the time you finish this module, you will be able to:
List the functionality of each of the Oracle data structures
Create an Abstract Data Type (ADT)
Create a nested table
Define a table with a VARRAY
Every organization has information that it must store and manage to meet its requirements. For example, a corporation must collect and maintain human resources records for its employees. This information must be available to those who need it. An information system is a formal system for storing and processing information.
An information system could be a set of cardboard boxes containing manila folders along with rules for how to store and retrieve the folders. However, most companies today use a database to automate their information systems. A database is an organized collection of information treated as a unit. The purpose of a database is to collect, store, and retrieve related information for use by database applications.
Database Management System (DBMS)
A database management system (DBMS) is software that controls the storage, organization, and retrieval of data. Typically, a DBMS has the following elements:
Kernel code: This code manages memory and storage for the DBMS.
Repository of metadata: This repository is usually called a data dictionary.
Query language: This language enables applications to access the data.
A database application is a software program that interacts with a database to access and manipulate data. The first generation of database management systems included the following types:
Hierarchical: A hierarchical database organizes data in a tree structure. Each parent record has one or more child records, similar to the structure of a file system.
Network: A network database is similar to a hierarchical database, except records have a many-to-many rather than a one-to-many relationship. The preceding database management systems stored data in rigid, predetermined relationships. Because no data definition language existed, changing the structure of the data was difficult and these systems lacked a simple query language, which hindered application development.

redpajama_set_name: RedPajamaCommonCrawl


text:
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Hajiyev: Azerbaijan continued its successful foreign policy under President Aliyev's leadership this year too
Hajiyev: Azerbaijan continued its successful foreign policy under President Aliyev's leadership this year too Political and military events
Azerbaijan has continued its successful foreign policy under President Ilham Aliyev`s leadership this year too, reads an article headlined "Strategic diplomacy pursued by President Ilham Aliyev and achievements of our foreign policy" by head of the Department of Foreign Policy Affairs of the Azerbaijani Presidential Administration Hikmat Hajiyev.
"The head of state pays constant attention to foreign policy issues, defines priority tasks facing our diplomacy, and ensures their planned and continued implementation. Not every state on the world map is able to pursue an independent foreign policy like Azerbaijan," said Hajiyev.
The article reads:
Addressing the January 2018 meeting of the Cabinet of Ministers dedicated to results of socio-economic development of 2017 and objectives for future, President Ilham Aliyev said: "Azerbaijan is today one of the countries on a global scale that pursues an independent policy. There are not too many countries like that. In particular, it is not typical of small countries in terms of population and territory. We are following the path of independence. A free and independent life is above everything for us."
It is President Ilham Aliyev's firm will, strong personality, deep and strategic vision, balanced and agile decisions and farsighted policy that allow Azerbaijan, a relatively small state, to pursue an independent foreign policy.
Azerbaijan is pursuing its independent foreign policy confronted by Armenia's ongoing military aggression, aggravation of contradictions and escalation of tension in international relations, activities accompanied by a gross violationof norms and principles of international law, emergence of new conflict zones in the regions close to Azerbaijan, growing threat of international terrorism and attempts to interfere in internal affairs of states as well as geopolitical difficulties of our region. Our country also faces continued disinformation campaigns and hybrid war.
As President Ilham Aliyev noted, there are no sources of internal threats in our country. Potential dangers are formed outside our country. The flexible, pragmatic and balanced multifaceted foreign policy pursued by the head of state serves to build a goodwill environment around the country and prevent and neutralize the threats and dangers coming from abroad. Azerbaijan is therefore today recognized as an island of stability and security in the region.
President Ilham Aliyev's meetings, high-level dialogue and discussions with the heads of neighboring and other states are of exceptional importance in pursuing an independent and flexible foreign policy based on Azerbaijan`s national interests. The head of state's foreign schedule is as tough and intense as in domestic policy and includes numerous visits and meetings. President Ilham Aliyev has paid 16 official and working visits to foreign countries in 2018, including Turkey, Russia, United Kingdom, Switzerland, France, Croatia, Belgium, Kazakhstan, Kyrgyzstan, Belarus and Turkmenistan. The presidents of Turkey, Iran, Russia, Italy, Tajikistan, Macedonia, Mongolia, Albania, Chancellor of the Federal Republic of Germany, prime ministers of Bulgaria, Georgia and Slovakia, member of the Presidency of Bosnia and Herzegovina made official and working visits to Azerbaijan as well.
Each visit on President Ilham Aliyev's agenda is of result-oriented and practical nature, and serves to develop mutually beneficial cooperation based on strategic interests.
President Ilham Aliyev's meetings with the heads of state of neighboring Turkey, Russia and Iran, which are held in a friendly atmosphere, his reciprocal visits and sincere dialogue with them are of crucial importance in developing our good neighborly relations. President Ilham Aliyev's visit to the European Union (EU) headquarters, his meeting with the President of the European Council Donald Tusk in Brussels and the conclusion of thePartnership Priorities document with the EU, as well as letters sent by the U.S. President to the head of state, and visits of the US high-ranking delegations to Azerbaijan have given impetus to the development of Azerbaijan's cooperation with the EU and the United States.
More than 90 agreements, joint declarations and other similar documents have been signed with foreign countries with the participation of Azerbaijani President Ilham Aliyev in 2018. These documents essentially contribute to expanding the legal basis of bilateral cooperation with other countries. Among the documents signed between President Ilham Aliyev and other heads of state were:
- The Convention on the legal status of the Caspian Sea;
- "Protocol of the seventh meeting of Azerbaijan-Turkey High-Level Strategic Cooperation Council";
- "The Joint ActionPlan for the Strategic Partnership between the Republic of Azerbaijan and the Republic of Serbia";
- The Joint Declaration of the President of the Republic of Azerbaijan and the President of the Republic of Tajikistan;
- "The Joint Declaration on priority areas of economic cooperation between Azerbaijan and Russia";
- The Joint Declaration of the President of the Republic of Azerbaijan and the President of the Republic of Belarus;
- The Joint Declaration of the President of the Republic of Azerbaijan and the President of Turkmenistan.
The signing of the Convention on the legal status of the Caspian Sea in 2018 is a joint achievement of both Azerbaijan and all the Caspian littoral states. Although the regional nations have been benefiting from the Caspian Sea and its resources for centuries, there had been no document regulating the legal status of the Caspian Sea. That's why the Convention, which was signed by the heads of state of the Caspian littoral states at the 5th Summit in Aktau on August 12, 2018, for the first time defined the legal status of the Caspian Sea and stipulated the rights and obligations of the littoral states in relation to the sea. As the head of state noted at the 5th Summit of the heads of state of the Caspian littoral states, the Convention defined the overall legal regime in the Caspian Sea.
Ensuring that Azerbaijan`s just position on the Armenia-Azerbaijan Nagorno-Karabakh conflict is set out in the signed documents is one of the top priority issues in President Ilham Aliyev's policy. Therefore, apart from defining the priority areas of bilateral cooperation, the documents reiterated support for the inviolability of the territorial integrity, sovereignty and internationally recognized borders of Azerbaijan and the settlement of the conflict on the basis of these principles, including the relevant resolutions of the UN Security Council.
Throughout the year, President Ilham Aliyev has held more than 230 meetings with foreign delegations in the country and abroad. But this doesn't include meetings with delegations from the cultural, social and sports fields. In his speeches at influential multilateral platforms such as Davos Economic Forum, which plays a crucial role in shaping the global economic, political and financial agenda, at the NATO Summit in Brussels as well as at summits of the Cooperation Council of Turkic-speaking States, Mid-Term Ministerial Conferences of the Non-Aligned Movement held in Baku and other prestigious events, the head of state has put forward Azerbaijan's fundamental vision for global and regional problems.
Diplomatic correspondence is an integral component of diplomatic relations. President Ilham Aliyev`s correspondence with world's leaders has included more than 750 letters and other diplomatic messages this year.
The year 2018 was also remarkable for the fall of the military junta led by Serzh Sargsyan in Armenia. The policy pursued by Azerbaijan under President Ilham Aliyev`s leadership, Armenia's isolation became crucial factors that brought about the collapse of Serzh Sargsyan's regime.
Azerbaijan, in the person of President Ilham Aliyev, has demonstrated strategic patience and high-level political culture in view of the political crisis in Armenia. The Armenian new political leadership`s attempts to change the format of the negotiation process and lay political claims have been prevented. The talk held between President Ilham Aliyev and Armenian Prime Minister Nikol Pashinyan on the sidelines of the CIS Summit in Dushanbe once again stipulated that Armenia and Azerbaijan are the parties to the conflict and the two parties will continue the negotiations. The Azerbaijani President`s next talk with the Armenian prime minister took place on the sidelines of an informal CIS summit held in Saint Petersburg. The Joint Statement adopted by the foreign ministers of Azerbaijan and Armenia together with the OSCE Minsk Group Co-Chairs at the OSCE Ministerial Council Meeting in Milan reaffirmed the continuation of the negotiations on the basis of the existing format and demonstrated the triumph of President Ilham Aliyev's diplomacy.
In this regard, President Ilham Aliyev`s constructive policy and commitment to solving the conflict through substantial negotiations is supported by the international community, and this support is openly expressed through public statements and during meetings.
The policy towards strengthening support for Azerbaijan`s fair position on the Armenia-Azerbaijan Nagorno-Karabakh conflict has continued this year. The Partnership Priorities Document signed between President Ilham Aliyev and President of the European Council Donald Tusk in Brussels emphasized support for the territorial integrity, sovereignty and inviolability of the internationally recognized borders of Azerbaijan.
The final communique adopted at the NATO Summit Meeting in Brussels with the participation of President Ilham Aliyev reiterated continuous support for Azerbaijan's territorial integrity and sovereignty and called for the settlement of the conflict on the basis of these principles.
President Ilham Aliyev pays constant attention to the release and return of our fellow countrymen Dilgam Asgarov and Shahbaz Guliyev to the motherland and continuously discusses this issue with the OSCE Minsk Group co-chairs, Personal Representative of the OSCE Chairperson-in-Office and other official delegations. All members of the international community, including the OSCE Minsk Group co-chairs, support the Azerbaijani President's humane proposal concerning the exchange of hostages between Armenia and Azerbaijan on the basis of "all-for-all" principle.
President Ilham Aliyev`s resolute and consistent policy also brought about Armenia`s marginalization in the Collective Security Treaty Organization. Although Azerbaijan is not a member of this organization, our country could not have remained indifferent to the policy pursued by Armenia, which abuses its status in the organization. This resulted in the dismissal of the Armenian representative, who was undermining the organization`s status, from his post of secretary general, and Armenia was not allowed to keep this office.
It is President Ilham Aliyev`s strategic diplomacy and logical foreign policy that ensures the improvement and strengthening of Azerbaijan`s international influence and weight, and its regional leadership role.
In his speech at the openingof the 5th Global Baku Forum, President Ilham Aliyev said: "All our initiatives aim at regional cooperation, stability and predictability, as well as the strengthening of peaceful coexistence and understanding among nations."
Azerbaijan is today contributing actively to addressing regional and global problems. With transregional transport and energy projects, Azerbaijan is assisting considerably the efforts to strengthen peace and stability both in the region and beyond. Guided by the principles of regional affiliation and responsibility, the country is cementing peace, stability and cooperation in the region through bilateral and trilateral cooperation mechanisms.
Azerbaijan stands for the establishment of the rule of law-based economic and political order in the international relations.
In accordance with the head of state`s strategic instructions, Azerbaijan will chair Non-Aligned Movement, which includes 120 countries, in 2019-2022. In his speech at the opening ceremony of Mid-Term Ministerial Conference of Non-Aligned Movement in Baku in April, 2018, President Ilham Aliyev outlined Azerbaijan`s presidency priorities in compliance with Bandung principles – the core principles of the organization – and the country`s vision for the strengthening of international peace and security.
The policy pursued by the head of state also transformed Azerbaijan into a globally important platform for strategic dialogue. Baku has been hosting regular meetings between the military leadership of the U.S. and Russia, NATO and Russia since 2017. In February, 2017, Baku hosted a meeting between the chairman of the Joint Chiefs of Staff of the United States and the chief of the General Staff of the Armed Forces of the Russian Federation. In September, 2017, the capital of Azerbaijan hosted a meeting between the chairman of the NATO Military Committee and the chief of the General Staff of the Russian Armed Forces.
There are nearly 200 countries in the world, which are members of the United Nations. But this meeting is held in Azerbaijan. There are nearly 50 countries in Europe. But this meeting is held in Azerbaijan. President Ilham Aliyev explained this: "There are several reasons for that. First of all, we enjoy trust. Azerbaijan is a very reliable partner, our words are complemented by our deeds, we fulfill all our promises and stand behind our words. On the other hand, there is respect for us. The policy we are pursuing today has earned us tremendous respect. Azerbaijan is treated with great sympathy. By pursuing an independent policy, we have been able to assert ourselves as an independent country in the true sense of the word. The third reason is that we have close ties with both Russia and NATO."
By hosting meetings in this format, Azerbaijan – as a worthy and responsible member of the international community – is making its contribution to strengthening global peace and security, arms control, reducing international tension and building strategic dialogue and mutual confidence.
Azerbaijan is making diverse contributions to international cooperation. Among them are our efforts to build cultural bridges, which encourages a better understanding between Asia and Europe, between Europe and the Muslim world.
At the conference of the Council of Europe Ministers responsible for Culture under the motto "Intercultural dialogue as a basis for peace and sustainable development in Europe and its neighboring regions", which was held in Baku in December, 2008, the President of the Republic of Azerbaijan put forward "Baku Process" initiative aimed at developing dialogue and cooperation between the Islamic and Western civilizations as well as between nations and cultures. "Baku Process", which celebrates its 10th anniversary this year, has already become an influential platform that plays a crucial role in intercultural and intercivilizational dialogue. The Humanitarian Forum, which is held regularly in Azerbaijan, including in 2018, is an important international format for discussing and addressing global humanitarian issues.
As a foreign policy sets a longer term strategy and objectives, the people of Azerbaijan will see the results and successes of someof the initiatives, which the head of state put forward in 2018, in the years to come.
Like previous years, 2018 has seen Azerbaijan`s independence and sovereignty strengthen under President Ilham Aliyev`s leadership. As the head of state said: "Present-day Azerbaijan is yet another evidence that independence is our greatest asset. Indeed, it is. Independence is our greatest asset, our greatest blessing, our greatest happiness. Azerbaijan`s independence is eternal."
source: Trend
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FrontPageMe.com is now not only able to offer you prints of your front pages but we have also enabled high resolution downloads. Now you can purchase a high resolution download and print your front page at home or take it to your local photo lab for printing. The resolution for a magazine is 3000 x 2400 pixels and will produce a 12x15 inch print.
The resolution for a newspaper is 3600 x 2400 pixels and will produce a 12x18 inch print.
Post to your Myspace, Facebook, blog etc.
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Home » Reviews » CD » T » Tommy Vitaly - Indivisible
Tommy Vitaly - Indivisible
Tommy Vitaly
by Daniel Stefanov at 31 May 2017, 7:48 AM
I grew envious of people who can still listen to symphonic, neoclassical or progressive metal. While I personally passed this stage a while ago, I vividly remember the year in which NIGHTWISH and AVANTASIA were the be-all end-all of my music taste. But I will not try to sell you the familiar bullshit story of how I "grew up", and began listening to thrash and black, because melodic metal was too "childish" or too "soft" for me. People don't stop listening to good music because they grow and pass onto something "better". They do it because the world makes them sad and angry with age, and in the rage of daily struggle, they lose the sensitivity to detail, and the patience required to appreciate it. And a SODOM song can much more easily find its way into that state of mind, than the tranquil, intricate and incantatory work of art, hereby under review.
Tommaso Vitali was not a musician that I was familiar with prior to being tasked with this review. I can say that I am closely familiar with the type: Luca Turilli, Axel Rudi Pell, Arjen Lucassen, Yngwie Malmsteen. Bearing the name of a famous 17th century classical composer, and hailing from roughly the same region in Italy, Tommaso Vitali does not disappoint, as he is a virtuoso with the guitar, up to the talent of the aforementioned legends, if not exceeding, and his compositions should really be reviewed by a more knowledgeable connoisseur of the fine arts than myself, as I can hardly do them justice. Now all those introductory words and disclaimers aside, let's dive into the album. The cover art is an underwhelming image of an "angel of death"-like figure with wing ornaments, over a cracked abstract black background. Something we could expect from an entry-level band, afraid to step too far from the approved metal tropes, not to scare the potential impulse buyers away. At first glance nothing in the image remotely resembles the essence of the music, or could be associated with the otherwise memorable and strong title.
The disc opens on the title song, "Indivisible", which eases the listener into the album with a generic intro, making a sharp turn into brave originality about 45 seconds in. The song definitely grabs the attention and raises the expectations for the rest of the album. Very prominent guitars and vocals carry the song, however often overshadowing the very pleasant drumming. Carsten Schulz does a lovely job carrying the vocal duties, however at some points feels a bit stretched during the verses. The backing vocals on the track add great depth, and combined with the tempo of the drums, constitute to creating the perfect opener for the album. "The Lodge" opens with an organ, immediately raising very pleasant associations with one of my favorite songs - HAMMERFALL's "Between Two Worlds". However, that's where the similarities end, as "The Lodge" is not a soft and melancholic ballad, but a pounding metal epic with great heavy guitars and exceptionally pleasant vocals by Apollo Papathanasio, whose style of singing immediately transported me back to 1975, when Ronnie Dio left his mark on the legendary titular album for RAINBOW. And though nobody can come close to Dio's extraterrestrial vocal capabilities, I can never not like something that so much reminds me of him.
"Duel" is an instrumental, and I really have nothing to say about it. Yes, it's technically impressive and I suppose compositionally worthy of note, however since I lack the musical education to appreciate either of those two aspects, I have to judge it as a simple listener, and to that ear it feels more like a "look what I can do" than an actual "I have something important to share and I'll do it in musical form", which instrumentals should be, in order to grab my attention. And I may ruffle a few feathers, but for an instrumental that gets my passing grade, look no further than MANOWAR's "Today is a Good Day to Die". "Macabradanza" immediately fixes the bad taste I was left with after "Duel", and yet again I am impressed. The song is a chemical perfection of so many distinct elements, that Tommy masterfully juggles with and manages to mix in an amazing melody and strong presence, further enhanced by the brilliant vocals of Roberto Tiranti and Chiara Manese. An amazing and memorable song with operatic elements and beautifully complementing voices. "Forever Lost" is slow and beautiful acoustic ballad. Can't really review a ballad, it's a song of the soul more than any other - every person has his own frequency of resonance, to which a ballad either adheres, or does not. To me personally, "Forever Lost" is brilliant and emotional, although some others may consider it nothing special, or even boring. Perfect vocals by Henrik Brockmann.
"Wings of Doom" is a typical fast power metal song, also heavily dominated by guitars. Very pleasant to listen to, if not too original, and again raising strong associations, this time to the style of early RHAPSODY OF FIRE. "Coraline" is a uniquely beautiful song, seemingly inspired by "Phantom of the Opera", among others. The song is rich and complex, moody like an AVANTASIA track, brilliantly performed by Jan Manenti, eerie, emotional and soaring - a true masterpiece in my eyes, and the second song on this album after "Macabradanza" that any band would be proud to have. "La Bestia" is another instrumental, this time slower and more atmospheric at start, and more rhythmic and energetic later on, definitely giving off more pleasant vibes than "Duel". "Sinner" is a fast and hard power metal track, bearing the familiar voice of Fabio Lione. As a fan of RHAPSODY, I was looking forward to Fabio's song, and was left a bit underwhelmed by the fact that he was given the only simplistic typical hard song on the album. It is a decent, energetic and powerful song, however I believe Fabio should have switched places with Carsten for "Indivisible", where his abilities would shine instead of being limited by "Sinner". Speaking of Carsten, he is back to finish what he started with the final track on the album - "Joan of Arc" - an anthem for our favorite badass lady of history. Again a very pleasant song, with just the right proportions of fast, epic, hard, and melodic. The back vocals reminded me of 90's ICED EARTH, while the very beginning bought me to another favorite song of mine - WASP's "Widowmaker". After an emotional mid-section, the song is very rhythmic and captivating and I can't help instinctively headbanging to it, which, after all, is the idea behind every metal album, right?
"Indivisible" definitely brought TOMMY VITALY on my radar. It is a very rich, very solid and complete release, that beams with inspiration, energy, complexity and emotion. "Indivisible", "Macabradanza" and "Coraline" are the high points of the album, and by high I mean truly soaring high - they far surpass the quality of material I have come to expect from some previously legendary bands. The album plays around familiar neoclassical and symphonic power metal, and develops a new meaning, utilizing the talents of a small army of guest vocalists, each performing admirably. This album makes me wish I could listen to music like that for days on end, like I used to in the old times. Alas, a new dawn rises and I feel compelled to blast OVERKILL. But "Indivisible" is an album I will be getting back to, and you should too.
Songwriting: 10
1. Indivisible
2. The Lodge
3. Duel (instrumental)
4. Macabradanza
5. Forever Lost (acoustic)
6. Wings of Doom
7. Coraline
8. La Bestia (instrumental)
9. Sinner
10. Joan of Arc
Andrea Torricini - Bass
Tommaso Vitali - Guitars, Keyboards
Alessandro Bissa - Drums
Carsten "Lizard" Schulz, Apollo Papathanasio, Gabriels, Roberto Tiranti, Chiara Manese, Henrik Brockmann, Alessio Gori, Jan Manenti, Fabio Lione - Vocals
Record Label: SG Records


Syrian Meal at Torridon Community Centre, February 2017 | Take One Action!
Living on the West Coast of Scotland, the word most people use is 'remote' and yes, it is remote physically but also you do feel less connected and affected by the wider world. This feeling made me realise that I had to be creative to ensure that issues that I care about did not get lost or ignored. The plight of Syrian refugees is one such issue. I wanted to somehow share concern and give people an opportunity to explore new things as well as discuss issues. A meal of Syrian food then was the obvious way and seeing the approach of Cook for Syria provided a bit more inspiration.
Adverts were placed in An Carranach based in Lochcarron and Gairloch News to spread the word, then Facebook and emails did the rest and the numbers started rolling in. I wondered if I could manage everyone and so appealed for some help and local cooks rose to the challenge of cooking a wide variety of Syrian food from chicken with freekeh and cod with zaatar to ma'amoul biscuits and baklava. The spread ended up being fantastic and almost all the 50 plus people who came had never eaten Syrian food before. The talk on the night was about the food, the event, the issues and challenges faced by refugees and ways in which a community like ours could support them.
People came from Torridon, Shieldaig, Lochcarron, Arrina, Gairloch and Kinlochewe. This diversity made people comment, " I usually know everyone who attends events at Torridon Community Centre, but I certainly don't know everyone here." New friends were made. A friend I see every week to play badminton, discussed aid and development in a way that we have never had the opportunity to before. A man visiting from Shetland (who turned out to be the locum minister) won a ma'amoul mould in the raffle and changed his whole sermon the next day to discuss Syria and passed the mould round to give everyone an opportunity to reflect on the plight of the refugees.
People are still coming up to me and telling me about Syrian food they have explored and tried to cook afterwards. So, in the end, raising nearly £1000 for Oxfam Syrian Appeal and Highland Supports Refugees was not the only outcome There was debate, shared food, new tastes, challenges and a shared sense that we are not necessarily powerless, even though we may still be 'remote'.


This is priceless!!! I love it. Did you shoot this on your D7000? The picture quality is fabulous.
Christine, I shot this on my little Flip video cam. I'd rather get watermelon juice on it instead of the good camera.
After your last watermelon post, I was in the grocery store and they had a pile of them right up front so I bought one for Emma. I was feeling quite pleased with myself when I headed out to the barn with it. Emma took one little nibble of it, wrinkled her nose and spit it out. I tried offering her a different piece and she actually scowled at me and left! Maybe it's real proof that you really can't buy good fruit in NY.
One of my favorite videos! I love the closeups of the equine muzzles (Wynonna's, not so much - sorry, Princess!). I feel as though I could touch them on my monitor and feel the softness.
I thought about your equipment, too. You had to be sticky. My Mom would "let" us go outside to eat watermelon. Then we "got to go swimming" in a big wash tub before we came back in the house. It took me years to figure it out. This music would have made it a party. This video makes me happy.


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Hands-on Review:
US Optics SVS 1-6x24mm Full Review
We test the new SPR style SVS scope from US Optics
By Melvin Ewing December 7, 2018
Manufacturer: US Optics
Model: SVS
Finish: Matte Black
Magnification Range: 1-6x
Objective: 24mm
Tube Diameter: 34mm
Eye Relief: 3.5" (89mm)
Click Value: .2 MIL
FOV: 107.5' - 18.65' @ 100 yards
Reticle: SVS MIL Scale
Focal Plane: 2nd
Weight: 22.2 oz (629gr)
Overall Length: 10.23" (260mm)
List Price: $ 1299.00
Street Price: $ 1150
Buy Here:
Earlier this year when we paid a visit to US Optics we were impressed with where the new company was going and we liked their new facility up in Kalispell Montana. We have since reviewed their B-Series B-17 scope and liked the new design, but that was not their latest scope. For that, you have to turn to the SVS 1-6x24mm scope that we have here for review. The SVS is a scope intended for an SPR (Special Purpose Rifle) and not a true sniper focused scope. But here at Sniper Central we do cover SPR, DMR, SSR and other rifles that may not be sniper rifles directly, but they relate to the sniping role and felt that this scope would be a worthwhile review. The scope we have for our evaluation is the SVS 1-6x with the SVS MIL Scale reticle.
As we mentioned in the B-17 review, the US Optics scopes arrive in a plain and simple white box with some basic documentation, an Allen wrench and a US Optics sticker. Nothing fancy, but everything you need. Our test scope also came already mounted in a ZroDelta mount which sets it up nicely for any of the MSR/AR rifles may want to use it on. Typically on a SPR the scope tend to be more compact, the initial impressions of the SVS are that it is large for its purpose, and seems to carry some weight to it as well.
The eyepiece is very large, both in diameter and in length and is very similar to the eyepiece on the B-17. The rear has the fast focus eyepiece that will cover the entire diopter range in about 1.3 rotations. It rotates smooth through that range, but becomes more stiff the further "in" the eyepiece is rotated and there is no indicator mark to keep track of where the lens is in that adjustment range. There is also no rubber ring to help protect the eye in case of a scope kiss. Though on a light recoiling SPR rifle this should not be a problem, and the 3.5″ of eye relief should be enough.
At the front of the large eyepiece is the zoom magnification adjustment ring which covers about the first half of the eyepiece in terms of length. There are some knurling indentions in the ring, but the large throw lever style tab is what will get used the most when adjusting the zoom power. The zoom goes from 1x through 6x and it is smooth through the entire range with moderate force required to rotate it. It is interesting to see that there literally are only two markings on the ring, 1 and 6. There are no numbers in between, so it is just a matter of guessing what the zoom power is on, which typically the guess will be off since scopes will have different spacing between each zoom power as you go up the scale. The reticle is also a 2nd focal plan reticle, which means it does matter what power you are set on for the MIL SVS reticle to be accurate. The good part is that for this scope, it is calibrated to be accurate on the highest magnification setting of 6x. So it makes it easy to just crank it up to the max power and use it there for the MIL markings.
The SVS is intended to be a compact SPR style scope, and with the large eyepiece, it reduces the amount of available tube in front of the eyepiece to be a relatively short 1.80″ to use for locating the rear scope mounting ring. The tube is 34mm diameter, which is perhaps a bit of overkill for a scope that is not intended to use or need a lot of dial in adjustments, which is what the larger tubes really give you. Of course, you do get some added weight, size, and heft with the larger tube as well. But there are no other advantages beyond "maybe" being a little stronger and providing a larger housing for which to place the objective lens while keeping a straight tube at the front.
The shoulder where the controls are located is a rounded design with elongated large flat spots on top of each location. The knobs for both the elevation and windage have dust caps on them, and like we have indicated already, an SPR optic is intended to use the reticle for most of its adjustments by holding off of the point of aim. This means after the initial zero is set on the knobs, they are generally left alone. This is good because the knobs on the SVS are not setup for pure sniping work.
Under the dust cap, the elevation knob is a flat design that is finger adjustable, though the setting cannot be seen from behind the scope. Additionally there are no indicator arrows showing which way is up, but just follow the numbers, they count up. There is some mild serrations on the knob to help with grip in inclement weather and there are markings on the very top of the knob. Each click is .2 MIL, which is an odd number, but again, the scope is not intended to have precision knobs for accuracy work. Just zero and then wing it from there. The clicks themselves have no slop, though each one is perhaps not at pronounced as we would normally like, but they are muted and should not accidentally move, especially with the cap on. Obviously, there is no need for a zerostop capability.
The windage knob is identical to the elevation knob, just mounted on the side. The clicks have the same feel and the markings are even the same. They likely are interchangeable in every way. Again, there is no direction indicator and we guessed that counting up was "RIGHT", and we were correct in that assumption. There really is not much more to report than that. The knob works, and it is simple. The scope is a non-adjustable parallax scope, so there is no focus control.
Instead of a focus control on the left, there is an illumination control knob. The scope features an illuminated 2 MOA dot at the very center of the reticle. The controls for the brightness is a rheostat style control. The control does not have specific clicks for brightness but rather just clicks in the off position and then rotates freely without clicks up to the highest brightness, which is visible in full daylight. It is a pain to have to rotate the knob all the way to where you want it every time you want to use the illuminated reticle, but the control is very smooth through its entire adjustment range. There is a cap on the very top of the knob that is the battery cover.
In front of the shoulders the tube is straight until the very end, which is what we prefer for these SPR style scopes. The tube extends another 3.00″ that can be used for locating the forward mounting ring. As we mentioned, the scope is somewhat large with its 34mm tube and large eyepiece and the weight is a substantial 1.4 lbs, but the construction quality appears to be high and the size and weight gives the impression that the scope is very durable. Sitting on top of a small carbine length M4, it looks rather significant, but sitting on a long gun with 26″ barrel, not so much.
Because this scope is not a true sniper type optic, our normal testing procedure, which you can read about here, is not as relevant. But we needed a way to test the quality of the manufacturing so we decided to move forward with the same lineup of tests, but somewhat abbreviated since the intended use of the scope is different. Keeping in mind the designed purpose of the scope is to zero, and then hold off for engagements, we tried to tailor our testing for that mission. Since the reticle plays a prominent role in this scope, let us take a moment to discuss it.
With the SVS MIL scale reticle, each of the hash marks on the left and right stadia represent 1 MIL increments. Extending down below the horizontal stadia the first two hashes do the same, representing 1 MIL each. Then the next hash down is an additional 2 MIL, making it 4 MIL down from the horizontal crosshair. Finally, there is another 2 MIL before the fat part of the stadia begins, giving 6 MIL of total vertical measurement that can be used. This allows for some basic MIL ranging capability if needed, but the full intent is to use those MIL marks for holding off if you know your ballistics. Additionally, the width of the two hashes below the horizontal stadia is to hold off in a 5 MPH or 10 MPH wind, though US Optics does not indicate what cartridge those wind hold offs are for. In reality, the reticle does not offer any real advantages over a basic reticle and we would probably even recommend the MIL Type 2 reticle that is also offered on this scope.
With the reticle being located on the 2nd focal plane, it means it must be set at 6x to be accurate. For a scope that is intended to be used in a SPR role where a rifle can be used for close-in engagements where you will want a lower magnification, and then may be used for holding off using the reticle at distance, it probably really should be located on the first focal plane where the magnification setting would not matter. A scenario where the rifle is being used during a patrol and the zoom is set at 2x or 3x and then a target pops up at 400 meters out and needs an immediate engagement, you would want to just use the optic without changing anything and hold your 3 MIL mark and engage. You may not have the time to change the power, or even may not remember to do it in a stressful environment.
For our shooting evaluations we used the scope on two different rifles to determine suitability. We used our normal 700P test rifle to do the testing of tracking and we mounted it to a M4 style platform to see how it worked on a more appropriate platform for what the optic was designed for. Our testing was done on a cold Montana morning with clear skies and the temps 5 above zero (Fahrenheit). The tracking on the scope worked well and showed good repeatability, but the knobs continued to baffle us a bit. Not only are there no direction indicators, but the markings on the scope did not correspond to the amount of adjustments being dialed in. The knobs showed 5 hash marks between each number, which in our mind seemed logical as each click was .2 MIL. The problem was that there were actually two clicks per hash, putting 10 clicks between each whole number. Obviously, doing the math, there were 2 full MILs of adjustment between each whole number, making the those numbers pretty much irrelevant.
Once we figured out the clicks per number, we fired one group, measuring about .75 MOA, and then dialed in 6 MILs of left and fired our second group, which was about the same size. Finally we dialed in 6 MIL of right and fired a confirming shot showing the tracking came back to where it was originally, which it did. Measuring the distance between the two groups we came up with 23.3″. At 100 yards, 6 MILs comes to 21.6″ which means we had 7.9% of error for the click sizes. This is larger than we like to see on a scope used for sniping, but for a scope designed for this application where it is zeroed and then left alone, it is not nearly as important, but still not the results we like to see either. To be transparent with the results, the group sizes were a bit larger than we typically see, which was likely due to the lower magnification, so there was certainly some added error in the results.
The optics on the scope are actually quite nice. We were able to see bullet holes on paper at 100 yards with only 6x of magnification and the glass was clear and bright from edge to edge. Mounting the scope to an M4 style rifle proved trickier than it should have been due to the attached rear sight aperture and the very large eyepiece on the SVS. We had to move it forward one additional notch on the rail than we would have liked, but that did give a micrometer of clearance to allow the rear sight to remain attached as well as the SVS. In this capacity, the scope does work well with good capability and durability. The built in throw lever is nice for quick magnification adjustments from just about any position. With the scope on lower magnifications, the front sight post of our test rifle does appear, but it is not a distraction and can aide in rapid target engagement.
With the SVS being the first of the new scopes designed under the new US Optics company, we wanted to see a solid design matched with excellent quality. The price puts this scope into a field with very strong competition and it needs to stand out in order to impress us. While the scope is well made, we see room for improvement in the design decisions. The SFP scope, knob layout and markings, illumination control and even the large size of the scope could all use improvement. Functionally, the scope will get the job done, we were just hoping it would lead off the new US Optics with some more wow than it did.
Sniper Central 2018
Tags: tactical scope, us optics
Darrin October 24th, 2019
I just picked one up secondhand. I am very excited to try it out compared to the razor as I've heard some say its clearer and lighter and others say differently.
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What is the Sexiest Cartridge of 2020? (Purely Based on how it Looks, not performance)
.308 Win (The 'girl next door')
.338 Lapua (Bold and Dangerous)
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Biografia
Si è laureata al DAMS dell'Università degli Studi di Torino, e poi diplomata alla Scuola Holden, fondata nel 1994 da Alessandro Baricco. Nel 2015 è stata tra gli autori della serie teatrale 6Bianca, realizzata dal Teatro Stabile di Torino. Tiene corsi di narrazione alla Scuola Holden di Torino. È rappresentata da Andrew Wylie, un famoso agente letterario statunitense, che ha conosciuto in occasione di una lezione da lui tenuta presso la Scuola Holden. Alcuni suoi lavori sono stati pubblicati su Linus e sul Corriere della Sera. Afferma di essere stata influenzata dal minimalismo di Raymond Carver.

La sua prima raccolta di racconti Un buon posto dove stare ha vinto il Premio Campiello nella sezione Opera Prima 2017. Nel 2019 pubblica il suo primo romanzo, L'impero della polvere, edito da La nave di Teseo.

Opere
 2017 - Un buon posto dove stare, Milano, La nave di Teseo, ISBN 978-88-93441-82-7
 2018 - Ora di cena, Milano, De Piante Editore, ISBN 8894228681
 2019 - L'impero della polvere, Milano, La nave di Teseo,  ISBN 8893448130

Note

Altri progetti

Collegamenti esterni

Studenti dell'Università degli Studi di Torino


Digg's Kevin Rose: "One Of Us Has To Leave"
Last summer we'd heard that the Digg board of directors was considering terminating Digg cofounder and CEO Jay Adelson. But everything was fine, said senior Digg employees, and the fact that the company moved Adelson out to California from New York at about that time was shown as evidence that the rumors were false. But one ominous conversation I had with Kevin Rose a couple of months later stuck with me. "One of us will leave the company," he told me, venting some frustration he had with Jay.
And that frustration led Kevin to slowly withdraw from Digg. He hasn't been seen regularly around the office "in about a year" says a source inside the company, and he had no specific job duties. Product had largely been taken over by Keval Desai, who joined the company from Google last November.
But Kevin's and investor's frustration over the direction of the company grew. V4 of Digg, which was supposed to launch in 2009, is only now being finalized.
So the board made their move, and Kevin is back at Digg in a full time role. Today the company announced that Jay has left the company, and Kevin Rose, who hasn't been completely focused on Digg day to day, is taking the acting CEO role.
Kevin is unsatisfied with V4 of Digg, we've heard, and plans to change it dramatically (look for more delays on the launch). Other minor frustrations also bubbled up, like the fact that Digg has no iPad strategy while other media companies are jumping in head first.
Still, it's an odd move. Even though Digg is clearly not on the same trajectory as Twitter and some other companies, they are profitable and are on track to hit $30 million in revenue this year. So whatever happened at Digg seems to be largely a personal issue between Kevin and Jay, and the board had to make a decision. They apparently made the decision they had to make. Digg without Kevin Rose isn't really Digg any more. But it may be hard for the company to find a high quality CEO to take Jay's spot, knowing that Kevin is really the guy who runs the company.
phase, I feel that now is the right time.
are today if it wasn't for you.
apps for the iPhone and Android.
excited about the next five years, big things coming!