text:
Endothelial progenitor cells: a new player in lupus?
DOI: 10.1186/ar3700
© BioMed Central Ltd 2012
Published: 20 February 2012
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DOI: 10.1186/ar3700
© BioMed Central Ltd 2012
Published: 20 February 2012
Patients with systemic lupus erythematosus (SLE) have a greatly increased risk of cardiovascular disease. There is growing interest in the link between vascular damage and lupus-specific inflammatory factors. Impaired endothelial repair could account for the endothelial dysfunction in this patient group. This review describes the contribution that endothelial progenitor cells could play in the pathogenesis of premature vascular damage in this disease. The methods of isolation, detection, and characterization of endothelial progenitor cells, together with their potential role in repair of the endothelium and as a therapeutic target in SLE, are discussed.
Accelerated atherosclerosis is well recognized in systemic lupus erythematosus (SLE). The striking incidence of mortality associated with coronary heart disease (CHD) in SLE was first reported over 30 years ago by Urowitz and colleagues [1]. This observation has since been confirmed in several studies, and, overall, women with SLE have a fivefold to sixfold increased risk of CHD in comparison with women in the general population [2]. In addition to having an increased overall risk, patients with SLE are susceptible to CHD at a younger age than would be expected [2, 3]. The exact etiology of arthrosclerosis in SLE remains poorly understood, and while traditional cardiovascular risk factors are likely to be contributory, they do not appear to fully explain the excess clinical CHD observed [4].
SLE has been shown to be an independent risk factor for endothelial dysfunction [5]. The vascular endothelium is the largest organ of the body and comprises a highly dynamic single layer of endothelial cells (ECs) that are pivotal in the regulation of vascular tone and that have essential anti-thrombotic and barrier functions. Endothelial dysfunction represents a state of deviation from normal to a vasoconstrictive, procoagulant, platelet-activating, and anti-fibrinolytic state and is thought to have a key role in atherosclerosis and related diseases. Though found to be present in all stages of plaque progression, endothelial dysfunction is believed to be the key triggering factor in the initiation of atherosclerosis [6].
Endothelial progenitor cells (EPCs) represent a heterogeneous group of cells that are released from the bone marrow into the circulation and are thought to contribute to vascular homeostasis and endothelial repair. Although modulation of EPC numbers has been identified with cardiovascular disease or vascular trauma (which appears to be predictive of clinical coronary events in the general population), there is still much controversy regarding their true identity and role [7]. Mechanisms by which vascular damage is repaired are not well understood, but previous reports have suggested that two groups of ECs can be detected in the peripheral circulation of individuals with vascular damage. The first, a population of EPCs, is thought to be bone marrow-derived and involved in the repair of the endothelium. In addition, the vessel wall itself may be a source of progenitor cells involved in the repair process [8]. A second population of 'inflammatory' or 'activated' ECs is thought to have been shed from the endothelium following an insult and this population may generate endothelial microparticles derived from damaged ECs and have a potential role in cell signaling [9]. It is therefore believed that damage to ECs can result in endothelial dysfunction and this is thought to be critical in the formation of atheroma [6]. Understanding endothelial repair is a vital step toward developing targeted therapies for this organ system and will enhance our understanding of the mechanisms of atherosclerosis in SLE. EPC quantification may provide a useful marker to aid risk stratification within the context of SLE, in which the Framingham risk prediction model would appear to underestimate the risk of clinical CHD. The purpose of this review is to highlight the controversy surrounding the current nomenclature and definitions used in this field, so that we can strive toward reaching a consensus on the true identity and the role of this circulating cell type. We will focus on what is known about EPCs in the context of SLE and discuss how we may move toward exploiting this knowledge to reduce vascular complications in SLE.
EPCs were first reported by Asahara and colleagues [10] in the late 1990s as CD34+ mononuclear cells with the ability to form island-like colonies in culture. These bone marrow-derived cells were shown in a mouse model, under the influence of vascular endothelial growth factor, to have the ability to incorporate into blood vessels with experimentally induced ischemia [11]. These landmark experiments have given an important insight into circulating angiogenic cells and the biology of vascular repair. Two key methods have been used to identify EPCs. The first aims to identify cells with specific surface markers for EPCs by using flow cytometry, and the second addresses in vitro cell culture characteristics.
Flow cytometry has been shown to have good sensitivity, specificity, and reproducibility [12], and several groups have used fluorescently conjugated antibodies to specific cell surface markers for analysis and identification of EPCs. The choice of surface markers for this cell type is the subject of much debate, and a variety of surface markers to identify EPCs have been used by different groups, as reviewed by Timmermans and colleagues [13]. The majority of studies using flow cytometry have used at least one surface marker to identify a cell of immaturity (from the broad hematopoietic cell lineage) and at least one marker to identify a cell from the EC lineage. Additionally, markers to identify cells originating from a myeloid lineage have been studied.
The most widely used marker to identify immaturity is C34 positivity. CD34 is a 110-kDa surface marker expressed on hematopoietic stem cells; however, the exact origin and signals for differentiation of these cells remain unclear. CD34 can be detected on approximately 0.1% of circulating mononuclear cells and is thought to act as an adhesion molecule related to endothelial and hematopoietic cells [14]. CD133 is a 120-kDa glycoprotein expressed on progenitor and hematopoietic stem cells [15]. The exact function of CD133 is not clearly understood; however, the protein is thought to identify an immature population of EPCs. CD133 has been detected on a subpopulation of CD34+/VEGFR2+ cells in the immature phase and has been shown to be no longer expressed on mature CD34+/VEGFR2+ in vitro, leading to the conclusion that CD34+/CD133−/VEGFR2+ cells represent a more mature differentiated population of ECs and that CD133 is a marker of 'early' EPCs [16]. It is possible that CD34+/VEGFR2+ and CD133+/VEGFR2+ represent different subtypes of EPCs and that CD34+/CD133+/VEGFR2+ can be used as a restricted EPC phenotype. One major disadvantage is that these triple-labeled cells represent a population of cells that are very small and therefore difficult to quantify reliably.
It is widely accepted that EPCs express vascular endothelial growth factor receptor-2 (VEGFR2) - or kinase insert domain receptor (KDR) in humans - and the roles of the VEGF receptor family in angiogenesis and vasculogenesis are well recognized [17]. Other endothelial antigens include CD31 and von Willebrand factor. CD31 or platelet endothelial cell adhesion molecule-1 (PECAM-1) is known to have roles in angiogenesis, platelet function, thrombosis, and regulation of leukocyte migration through vascular walls [18]. von Willebrand factor has a role in platelet adhesion to the vascular wall injury and is a carrier protein of coagulation factor VIII [19].
Subsets of CD14+ mononuclear cells have been shown to express EC markers such as CD31 [20] and, following stimulation by angiogenic factors, express von Willebrand factor and KDR [21]. CD14+/CD34+ cells display clonogenic properties in vitro, and importantly several recent studies have shown that CD14+ cells contribute to vasculogenesis [22, 23]. Additionally, clinical correlations of CD14+ subsets suggest a reduction in the number of patients with left ventricular dysfunction [24]. However, in contrast to CD34+/CD133+ cell numbers, CD14+ cell numbers appear not to be reduced in patients with clinical CHD or related risk factors [25]. While myeloid progenitor cells are detected in the circulation and appear to share many EPC characteristics, preliminary clinical studies would suggest a functional distinction between these subsets.
Another important factor to consider is the units in which cell populations are expressed. Some studies have favored expression of cells as a count per unit of volume of blood. EPCs are estimated to represent between 0.0001% and 0.01% of peripheral cells, making them a 'rare event' in flow cytometric analysis. Given the rarity of these events in peripheral blood and the variations in hemodilution between individuals (particularly in patients with cardiovascular disease), this measure can be misleading. Others have identified the proportion of total cytometry events acquired. This approach allows the enumeration of a proportion of a consistent number of cells counted by using flow cytometry (for example, proportion of 500,000 labeled cells analyzed). Quantifying the total number of cells may better take into account the potential for lymphopenia in patients with SLE.
Identification and quantification of EPCs by using flow cytometry can be challenging. Despite this, associations with disease states, including coronary heart disease, have been reported [7]. Specific and sensitive markers and properties to discriminate and definitively distinguish subsets of EPCs within the hierarchy of progenitor cells from mature ECs are beginning to emerge, and it has been wisely suggested that the field should adopt alternative terms for each specific subset. An alternative approach has been to identify viable cells with proliferative capacity in culture.
Early- and late-outgrowth cells share a number of features, including uptake of Dil-acLDL and expression of CD31, but differ with regard to surface expression of CD133. They are likely to represent EPCs at differing stages of maturation. It should be noted that EPCs identified by using cell culture are unlikely to represent the same cells identified by using flow cytometry; however, with the aid of proteomic studies, knowledge of the precise nature of these differing EPC subtypes is becoming more refined [28]. The ultimate aim of understanding EPC biology rests with elucidating their role in vivo and whether they might be prognostic or diagnostic factors. Several groups have successfully used CFU number as a biomarker in several different disease states, including CHD-related diseases [29] and inflammatory rheumatic diseases [30], so furthering our understanding of the in vivo role of these subsets of circulating progenitor cells holds considerable promise for their clinical application.
The observations reported by Asahara and colleagues [10] undeniably resulted in a paradigm shift within the field of vasculogenesis by highlighting the role of EPCs in vascular repair. Prior to experiments conducted by Asahara and colleagues in 1997, it was largely believed that 'vasculogenesis' or the de novo formation of vessels from uncommitted precursor cells occurred only in the developing fetus. However, more than a decade after the initial landmark experiments, there remains a lack of standardization regarding the identification and definition of EPCs. The use of differing surface markers and cell culture techniques between studies makes comparison of results difficult. Many groups have used CD34, CD133, and VEGFR2 surface markers in various combinations and successfully identified inverse correlations to disease states; however, recent reports have challenged the origin of cells with these markers and provide evidence that some of these cell populations, initially described as EPCs, are in fact myeloid-derived hematopoetic precursors [31]. Some investigators have advocated the incorporation of a common leukocyte marker CD45 within flow cytometric analysis and suggested that EPCs can be identified only within the CD45− fraction of cells [32].
Cells enumerated by using flow cytometry are insufficient in number to allow the biology of the EPCs to be examined. Culture methods provide a means by which a large number of cells can be isolated but may not be an accurate reflection of EPCs in the in vivo situation. In addition, recent studies have demonstrated that other immune cell types may have the ability to mimic the morphological characteristics of EPCs in culture [33, 34]. A degree of plasticity at the progenitor cell level in response to differing biological signals may explain some of these findings. It is possible that cells identified as EPCs are not directly incorporated into the regenerating endothelium but exert indirect but equally important angiogenic paracrine effects that result in endothelial repair [35]. Clearly, there is a need for studies to examine the biology of EPCs as well as elucidation of homing and differentiation signals to enable a better understanding of this unique cell type and the role of EPCs in health and disease. More methodological consistency and evidence of robust reproducibility and reliability of techniques are needed in future studies with clinical outcomes.
Within the human clinical setting, a recent study has demonstrated positive outcomes in seven out of nine patients who have critical limb ischemia and who were able to avoid amputation following the intramuscular injection of autologous CD133+ cells into the affected limb [36]. Similar results have been observed by other groups that used autologous peripheral stem cells or unselected bone marrow mononuclear cells [37, 38]. Importantly, these studies have demonstrated the safe use of cell therapy methods. Within the context of CHD, several clinical trials in the last 5 years have assessed the effectiveness of cell therapy as an adjunct to best-available care after an acute myocardial infarction. A controlled trial demonstrated short-term improvement of left ventricular function following intracoronary infusions of autologous bone marrow progenitor cells and sustained clinical benefit with reduced rates of death, clinical coronary event, and heart failure at 2 years of follow-up [39]. One small controlled study undertook intracoronary infusions of enriched CD133+ cells and demonstrated a small short-term (4 months) benefit of left ventricular function but noted an increase in coronary events (11 compared with four in the control group) [40].
Cell therapy is a growing and intriguing field, and there is evidence in several animal models that stem cell transfusion and systemic transfusion of expanded ex vivo EPCs can induce functionally intact endothelial regeneration [41]. Future studies need to consider source, purification methods, timing, and dosing of cell infusions. The sample sizes to date have been too small to assess the influence of baseline infarct size or severity of left ventricular dysfunction. Although the benefits observed to date have been modest, cell therapy in the context of acute myocardial infarction appears to be safe and shows much promise. The long-term efficacy and safety require further clarification. Whether stem cells do indeed contribute to vasculogenesis directly or result in cardiomyocyte replenishment or mediate an effect indirectly via trophic effects is not clear from clinical cell therapy studies in CHD but may be elucidated by taking a step back to laboratory experiments.
Endogenous factors that influence the number and function of EPCs are of much interest. Exposure to different lifestyle factors and several pharmacological agents has been shown to influence EPC levels. Both smoking cessation and increased physical activity have been shown to be beneficial to EPC number [42, 43]. Studies have demonstrated an increase in EPC number following administration of HMG-CoA (3-hydroxy-3-methylglutaryl-coenzyme A) reductase inhibitors independently of cholesterol reduction and this might be another mechanism by which statin medications exert a cardioprotective effect [44]. Angiotensin-converting enzyme inhibiting agents and angiotensin 2 receptor blockers have also been shown to have a positive effect on EPC number and function in the clinical setting [45]. Other pharmacological strategies that have been shown to enhance EPC number include chemokines and cytokines such as erythropoietin and VEGF [46, 47].
Endothelial progenitor cell measurement in systemic lupus erythematosus
Number of patients
with SLE
EPC definition
Main findings
15 with SLE
↓ CD34+, ↓ CD34+KDR+ in SLE
Westerweel et al. [49], 2005
15 controls
EPCs inversely correlated with cholesterol
↑ EPCs in hydroxychloroquine users
↑ CD34+ apoptotic cells in SLE
135 with SLE
(95% were women)
↓ CD34/CD133+ in SLE
Denny et al. [50], 2007
EPCs correlated with disease activity
60 controls
(55% were women)
Impaired differentiation to EC
EPCs have increased IFN-α expression in SLE
44 with SLE
↓ CD34+, CD133+, CD34/CD133+ in SLE
Moonen et al. [51], 2007
35 controls
↓ CFUs in SLE
No correlation with SLE factors
70 with SLE
↓ CFU-Hill in SLE
Lee et al. [56], 2007
31 controls
↓ CD34/KDR+ in SLE
EPCs inversely correlated with hsCRP
No correlation with CHD risk factors or SLE factors
High IFN-I levels associated with impaired endothelial function in SLE
31 with SLE
Grisar et al. [54], 2008
14 controls
↔ CFU-Hill
28 with SLE
↔ CFU-Hill
Ablin et al. [55], 2010
50 controls
No correlation with CHD risk factors or SLE factors
19 with SLE
↓ CD34/KDR+ in SLE
Ebner et al. [57], 2010
19 controls
Late-outgrowth colonies
↑ KDR/CD133+ in SLE
↔ Late-outgrowth colonies
17 with SLE
(100% were women)
↓ CD34/CD133/KDR+ in SLE
Baker et al. [52], 2011
13 controls
(38% were women)
No correlation with coronary artery calcification score in SLE
35 with active SLE
Late-outgrowth colonies
↔ CD34/Dil-acLDL/UEA
Deng et al. [53], 2010
35 controls
↓ proliferation, adhesion, and migration in SLE
No correlation with SLE factors
Other groups have also shown that EPC number, as measured by flow cytometry, is similar in SLE and controls and therefore focused on CFU formation. Grisar and colleagues [54] studied 31 females who had SLE and who were 35 (± 2) years old and compared them with 14 healthy female controls who were 39 (± 5) years old. The authors found no difference in CD34+/CD133+/KDR+ cells between SLE and controls. EPCs did appear to correlate with previous renal disease but not with other clinical parameters. The authors also reported on CFU number in 13 patients with SLE and 12 controls (ages were not reported in this subgroup) and found that CFU number was similar between the two groups. However, the authors reported a reduction in migratory and adhesive properties of cells in patients with SLE [54]. Ablin and colleagues [55] reported no significant difference in CFU number of 28 patients who had SLE and who were 38 (± 15) years old and 50 controls who were 43 (± 18) years old. Patients with SLE included males, and patients with a history of high-dose steroid, cyclophosphamide, or mycophenolate mofetil use were excluded, suggesting that the group studied may have been of a 'milder' phenotype. The authors did note an impaired adhesion of cells to fibronectin in patients with SLE, and this was interpreted as a marker of impaired function. CFU number or adhesion scores did not vary with disease activity. Similarly, Lee and colleagues [56] enumerated CFUs from 70 patients with SLE and 31 controls who had median (interquartile range) ages of 35 (27 to 45) and 36 (26.5 to 44) years, respectively. Ninety-two percent of patients with SLE and 84% of the controls were female. The authors demonstrated that the significantly reduced number of CFUs in SLE compared with controls was independent of leukopoenia. The authors also quantified CD34+/KDR+ cells by using flow cytometry and demonstrated a reduction in patients with SLE compared with controls. Neither CD34+/KDR+ cells nor CFUs were found to have any significant correlation to disease-related factors or CHD risk factors. However, CFUs did have an inverse correlation with C-reactive protein [56]. Ebner and colleagues [57] measured EPCs in 19 women who had SLE and who were 36 (± 6) years old and in 19 female controls who were 37 (± 8) years old. The authors demonstrated reduced CD34+/KDR+ cells in SLE but an increased level of CD133+/KDR+ cells in comparison with controls. Clinical correlates were not analyzed. The authors suggested that low levels of endothelial damage may result in increased mobilization of immature CD133+/KDR+ cells.
Overall, studies of EPCs measured by using flow cytometry have consistently demonstrated a reduction in CD34+/KDR+ cells in comparison with controls [49, 56, 57]. Two studies have also demonstrated a reduction in CD34/CD133+ cells [50, 51]. Grisar and colleagues [54] measured the smaller population of CD34+/CD133+/KDR+ cells and found no difference between SLE and controls. It may be that CD133 expression is rapidly lost in this population of cells. Similarly, our group found no difference in the number of CD34+/CD133+ cells between 56 patients with SLE and 48 healthy matched controls (0.03% (± 0.02%) versus 0.02% (± 0.02%), P = not significant) but did demonstrate a significant reduction of CFUs in patients with SLE (7 (± 6) versus 12 (± 12), P = 0.05). Neither CFUs nor CD34+/CD133+ cells were related to SLE or CHD risk factors [58].
Possible explanations for the discrepancy of the findings between different studies may be related to small sample sizes, differences within the study population, or method of EPC isolation and identification. A crucial consideration is the difference in the methodology used by different groups to quantify cells. Some groups have included absolute counts per volume of blood [49], whereas others have measured percentage of the mononuclear cell population [54]. Most EPC quantification methods using flow cytometry identify cells within the lymphocyte gate or involve a lymphocyte separation step. However, lymphopenia among patients with SLE may possibly result in an over- or underestimation of EPCs in this condition. In contrast, it is also possible that cytopenias may result in bone marrow stimulation and the increased production of progenitor cells.
The results of culture studies have been more consistent, and whereas some studies have had small sample sizes, the larger of these studies [56] demonstrated a reduction in CFUs in SLE compared with controls. The smallest of the studies [51] included patients with a mild phenotype and did not find any difference in CFU number in patients with SLE, suggesting that CFU number may be related to overall inflammatory burden over time. The discordance between findings using CFUs and EPCs may provide complementary rather than contradictory results. It is likely that CFUs measure a distinct myeloid-derived cell (now termed early-outgrowth EPC) compared with the population of CD34+ or CD133+ cells measured by using flow cytometry, and this may explain the discrepancy observed when these two measures were used. CFU measures are also likely, to some extent, to be a reflection of EPC functional ability to migrate to a cluster of cells and adhere to fibronectin. It may well be that, while progenitors are generated in adequate numbers by patients with SLE, their ability to mature and function differs from healthy individuals, resulting in fewer effective cells in patients with SLE and thus contributing to increased endothelial dysfunction. This hypothesis is supported by the observation that the migratory and proliferative capacities of EPCs are both reduced in SLE [54, 57].
Studies in SLE to date have been too small to detect clinical correlates to EPCs or CFUs. All studies have been cross-sectional and primarily included patients with quiescent disease, although some groups have selected patients with active disease for study; however, the influence of inflammatory burden over time or vasculitic manifestations remains unclear. The effect of anti-metabolite therapies such as azathioprine and mycophenolate remains unclear, and it is possible that these drugs may be toxic to CD34+ cells. Furthermore, Grisar and colleagues [54] documented EPC dysfunction in patients receiving anti-malarial therapy, although the small sample size makes robust conclusions difficult.
An interesting link between interferon-alpha (IFN-α) and EPCs is emerging within the SLE literature and may provide a mechanistic explanation for some observations. IFN-α is a member of the type 1 IFN cytokine family. These proteins have a role in immune defense, and increased levels are observed in the context of viral infections. They also have a role in physiological growth and differentiation [59]. IFN-α has been demonstrated to inhibit angiogenesis and vascular tumor growth [60]. Increased levels of IFN-α can be detected during a flare in SLE and have a central role in SLE pathogenesis [61]. Direct quantification assays of IFN are unreliable, and therefore downstream effects of IFN are used as surrogate markers. Lee and colleagues [56] demonstrated a reduction of CFU formation in those SLE patients with high expression of the IFN-I-stimulated gene MX1 (n = 19) and an inverse correlation of MXI with CFUs. Importantly, high IFN-I levels were associated with impaired endothelial function as measured by using peripheral arterial plathysmography [56]. Similarly, Denny and colleagues [50] demonstrated that supernatant from SLE ECs caused increased induction of IFN-inducible genes in comparison with healthy controls. Furthermore, the addition of recombinant IFN-α had a toxic effect on CD133+ cells in culture, resulting in CD133/CD34+ apoptosis. The authors used an anti-IFN-α monocloncal antibody to block IFN pathways in SLE EPCs in culture and demonstrated a normalization of function [50]. In addition, studies from the Kaplan laboratory [62] enabled the proposal of an interesting concept by using data from NZB/W lupus-prone mice: the authors showed that type I IFNs may play an important role in premature vascular damage and, potentially, atherosclerosis development in SLE. Based on the findings from a study by Lian and colleagues [63], they suggest that the bone marrow niche may be exposed to elevated levels of IFN more than other peripheral compartments and that this, in turn, could effect EPC properties with regard to their mobilization and homing to damaged tissue [63]. These early observations require further investigation as they may provide a pathway to restoration of EC function in SLE.
Initial findings from studies suggest the potential use of EPCs as a novel biomarker in risk stratification of CHD or some insight into future organ-specific therapeutic targets in SLE. However, many questions remain unanswered. Larger studies are required to verify these preliminary results and provide robust conclusions, in particular, to ascertain the influence of drugs such as statins. Longitudinal studies that focus on assessment before and after commencement of anti-metabolite therapies are needed. Given the low prevalence of SLE and diversity of clinical manifestations and therefore exposures, it is envisaged that multi-center collaborations should be encouraged.
Several groups have demonstrated reduced EPCs as measured by culture methods in SLE, but the precise characterization of EPCs requires further clarification of the mechanisms underpinning abnormalities in EC function (for example, homing signals to sites of damaged endothelium require further investigation). To date, studies have compared patients with SLE with healthy controls. However, a more relevant comparison group may be a cohort with another chronic inflammatory condition to elucidate the relative contribution to atherosclerosis in SLE.
Studies have suggested that type I IFN may contribute to EPC dysfunction in SLE and may suggest a potential role for their rescue by type I IFN-blocking agents (either IFN-antagonizing antibodies or receptor blockers) currently under development. Implications of promoting vasculogenesis/blocking type I IFN, however, need to be considered in the wider clinical context. There is potential for exacerbation of viral diseases or retinopathies. Also, the effect on tumor formation in this vulnerable patient group or the effect on manifestations such as inflammatory arthritis, in which it is thought that pathological angiogenesis occurs, is unknown.
Laboratory observations to date would suggest that there is an excess of EPC dysfunction in SLE, and clinical studies in the 'general' population would suggest that this can be of relevance to clinical coronary events. However, within SLE, prospective studies using clinical outcomes are required (a) to determine the consequence of low EPC number, (b) to establish whether the ex vivo situation is of relevance and reflects in vivo effects, (c) to determine whether low EPC number does contribute to an excess of CHD, and (d) to assess whether therapeutic targeting of EPCs will enhance vascular repair and improve long-term outcomes in SLE.
colony-forming unit
coronary heart disease
Dil-labeled acetylated low-density lipoprotein
endothelial cell
endothelial progenitor cell
kinase insert domain receptor
systemic lupus erythematosus
vascular endothelial growth factor
vascular endothelial growth factor receptor-2.


text:
On August 8th, at 6:59pm, the homicide suspect, Matthew Clement Bell, was taken into custody without incident. A citizen called the police stating he was at the Lake Morton Coin Laundry, 815 E. Palmetto Street. Uniformed patrol officers checked the location and arrested Bell. No additional information at this time.
On Friday, August 7, 2015, at approximately 10:57 p.m. the Lakeland Police Department responded to a disturbance at 720 Johnson Avenue, Lakeland, Polk County, Fl. Uniform officers discovered that two individuals had been stabbed, and the known suspect had fled the scene.
Peter Latoski, 44 years old, suffered a single stab wound and his injury was serious, but not life threatening. Mr. Latoski identified the suspect as Mathew Bell, 44 years old. He indicated that a disturbance occurred at the rooming house and Bell was asked to leave the property. When Bell refused, the second victim, Mario Acosta attempted to escort Bell off of the property. That led to a fist fight at which time Bell introduced a knife and stabbed Acosta. Mr. Latoski attempted to intervene and was stabbed once by Bell. Bell then fled the scene on foot and was not apprehended.
Mr. Latoski and Mr. Acosta were transported to Lakeland Regional Health Hospital and Acosta later died from his injuries. Detectives from the Violent Crimes Unit responded to investigate and they obtained a warrant for Bells arrest on 1st Degree Murder & Attempted 1st Degree Murder. Bell's has not permanent address and is listed at large at this time.
Victim: Peter Latoski, 44 yrs old, 720 Johnson Avenue, Lakeland, Fla.
Decedent: Mario Acosta, 58 yrs old, 720 Johnson Avenue, Lakeland, Fla.
Suspect: Matthew Clement Bell, 44 yrs old, No permanent address. Hgt. 5'07", WGT 160, Brown hair, blue eyes. Bell was last seen wearing blue jeans with a black and white shirt. There is an active warrant for his arrest on 1st Degree Murder & Attempted 1st Degree Murder.
Anyone with information on the whereabouts of Matthew Bell is asked to contact the Lakeland Police Department at 863-834-6900 or Crime Stoppers at 1-800-226-8477. To remain anonymous and be eligible for a cash reward, you must contact Crime Stoppers.
At approximately 6:45pm on Saturday, March 21, 2015, the victim, Shavar Lewis, 37 yrs old, and two other arrived at 1135 Martin Luther King Avenue in search of a subject. At this time, Lewis and witness Antonio Callaway became involved in a physical altercation. Diedre Callaway exited the residence with a steak knife swinging her arms and stabbed Shavar Lewis as he was fighting with Antonio Callaway on the ground. Lewis was heard by a witness saying, "She's stabbing me!" A witness, Jerreail McLeod, retrieved a handgun from within his vehicle and fired several rounds into the air to get the crowd to scatter.
McLeod then drove Lewis to Lakeland Regional Health to be treated. On Sunday, March 22, Lewis was pronounced deceased by LRH staff at 4:22 pm. On Monday, March 23rd, an autopsy was performed on Lewis and the Medical Examiner concluded that Lewis died as a result of a single stab wound to the left side of his back. The wound was consistent with that having been caused by a steak knife with a 5" to 6"" blade.
On March 21st, the Violent Crimes Unit responded to 1135 Martin Luther King Ave and to the hospital to investigate the stabbing. Detectives continued to follow-up with leads and interviews on Sunday and Monday and they identified Diedre Payne Callaway, 52 years of age as the suspect.
On Monday, March 23, 2015, Detectives obtained an arrest warrant for Diedre Payne Callaway for 2nd Degree Murder in the stabbing death of Shavar Lewis. At approximately 9:28 p.m. Diedre Payne Callaway was taken into custody at her residence located at 3120 Santa Fe Trail, Polk City, Florida. The PCSO assisted with the arrest which was uneventful.
Tyrone Sedgewick Davis
The Lakeland Police Department needs help in locating Tyrone Davis.
On February 18, 2012 at 11:23 p.m., Lakeland Police responded to 1202 Jewel Avenue in reference to a person being shot. Upon arrival, officers found Daylon Oshae Easton, 17, (b/m 05/05/1994) on a living room couch with a gunshot wound to the head. Several individuals were in the home at the time, however no one could provide information on the shooting.
Daylon Easton died Monday, February 20, 2012 as a result of his injuries.
If in contact with the subject approach with caution he is known to be armed with a firearm.
If anyone has information on the location of Tyrone Davis, please contact the Lakeland Police Department at 863-834-6900, or Crime Stoppers at 1-800-226-8477. To remain anonymous and be eligible for a cash reward, you must contact Crime Stoppers.
On Monday, December 29, 2014, at 11:12 a.m., the Lakeland Police Department responded to 1935 Crystal Grove Drive #53 to assist PCEMS call of a child not breathing. The baby, Princeton Graham, 5 months old, was in the custodial care of his biological father, Robert Graham and Graham's girlfriend.
Graham was in apartment #61, babysitting other children and his baby. Graham advised he was attempting to feed the baby formula and the baby began to choke. Graham said he turned the baby over and administered several back blows to the baby's back to stop it from choking. Graham then took the baby to apartment #53 were the resident there called 911.
On December 31, the baby, Princeton Graham, succumbed to his injuries at St. Joseph's Hospital in Tampa, Florida.
On January 2nd, an autopsy was performed and the findings of the medical examiner were that Princeton Graham died as a result of "Shaken Baby" caused by blunt force head trauma from assault.
Detectives stated that the father had admitted to overly rough playing with the baby on December 28th by slamming the baby on the bed, bouncing it on his knee and shaking the baby for about four minutes.
The father, Robert Graham knowingly and willfully abused the baby which resulted in his death. He was arrested on January 8th, without incident at his residence and charged with Aggravated Child Abuse, F1 and Manslaughter, F2.
Arrested: Robert Donte Graham, DOB 11/3/91, 8128 Simpson Lane, Lakeland, Fla.

subset: commoncrawl


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Publisher's Description
Over 16.5 million Americans practice some form of yoga. Many are Christians who are looking for a Christcentered alternative to their exercise routine.
From the creator of the popular PraiseMoves--The Christian Alternative to Yoga DVD, Laurette Willis offers three new 20minute workouts. In just 20 minutes a day, viewers can strengthen, tone, and increase flexibility while renewing their minds and nourishing their spirits on God's Word. Each posture is linked to Scripture to transform workouts into times of worship.
This new program offers ways to--
- reduce stress, improve circulation, and lose weight
- energize to optional Walkin' Wisdom Warmups
- learn God's Word through beautifully flowing Scripture Sequences
20 Minute PraiseMoves also includes an instructional segment with exercise tips, detailed posture moves, and postures for the beginner as well as the advanced PraiseMover.
Author Bio
Editorial Reviews
--Linda Stamps-Dissmore, director of women's ministries, Oklahoma District Council Assemblies of God
Product Reviews
susieqAge: 45-54Gender: female5 Stars Out Of 520 minute Praise MovesOctober 24, 2014susieqAge: 45-54Gender: femaleJust what I needed to help limber me up and get my arthritic body moving. The beginner moves are good for me. (Just for 'kicks' I tried the next level, no way! Will be awhile for me.) I enjoy it and is just the right amount of time for my schedule.
Tracy4 Stars Out Of 5May 18, 2010TracyIf you are looking for an aerobic workout, this is not. It is an excellent workout for developing flexibility, strength, and balance, things we often neglect or don't realize we are missing. I have used it as a warm up to my aerobic workouts and have been happy with the results.
Glenda Kilpatrick5 Stars Out Of 5April 21, 2010Glenda KilpatrickA much needed adaptation to the first Praise Moves DVD for working women who may not have a full hour for exercise. Very inspirational and spirit-lifting.
Kellie Miller4 Stars Out Of 5April 9, 2010Kellie MillerWhile I agree that this product may not impress those who regularly workout, it has been a wonderful find for me. Recently diagnosed with MS, this is one of the few workouts I can do without feeling ill afterward. This workout keeps me focused on the real "MS" (My Savior) rather than the frustrating "MS" (multiple sclerosis) that threatens to limit my preferred daily activities.
Ann Swanson3 Stars Out Of 5March 4, 2010Ann SwansonWhile this product is satisfactory, I was a bit disappointed. It is not what I expected. I did like the part where they quoted scripture along with the exercise, otherwise there was too much talking to suit me. I need a source with more exercise moves! I will not purchase any more of these.


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Thu., August 22, 2013 2:43pm
Safety Citations Issued At GA Manufacturing Plant
Federal officials have issued safety citations at a manufacturing plant in northern Georgia. Department of Labor officials announced Thursday that they've issued seven safety and health violations to a Dayton Superior Corp. plant in Braselton.
Full Story
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Come closer by BioHazardSystemWatch
©2012-2016 BioHazardSystem
Maki catta
My favourite animal...!
Amazing shot. I saw lemurs today and they were wild, I think they were only young
Lemurs! I love lemurs
adorable excellent photo
How adorable. Great shot.
awww it's sooooo adorable! I love lemurs!
almost looks like he's taking a self portrait! love it!! where was this taken??
Hey let go of my computer screen.
Great pic and very cute
Great pic and very cute
Hi Five to you too! LOL
Great shot!
Great shot!
Oh, hello there
I love this! ^_^
That's a really adorable piece.


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Noreen ONeill Foundation for Melanoma Research
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Jump to navigation
The Ocean Foundation is proud to be a part of the 1% for the Planet network, which connects businesses and nonprofits for a better world. If you own a business, consider joining 1% for the Planet, naming The Ocean Foundation as your beneficiary. Everyone wins!
For more information please visit www.onepercentfortheplanet.org.
The Ocean Foundation and Absolut Vodka began a corporate partnership in 2008 as part of Absolut's Global Cooling™ campaign. The multi-year green marketing campaign encouraged consumers to reduce effects of global warming and register to give one dollar of every bottle purchased to an eco charity. The proceeds were directed to restore seagrass beds around major metropolitan coastal areas. This partnership restored more than 4,000 square feet of damaged seagrass located at Knight's Key Bank in the NOAA Florida Keys National Marine Sanctuary.
Alaskan Brewing Co. (ABC) is dedicated to crafting really good beer, and really good philanthropy. ABC began a corporate partnership with The Ocean Foundation in 2007 to create the Coastal CODE Fund. 1% of all proceeds from their Alaskan IPA provide grants that promote the health of the Pacific Ocean, its coasts, and the waterways that lead to it. The Fund is made up of ABC employees who meet four times a year to review incoming grant proposals. Together, we have generated over $146,000 in grants.
From 2006 to 2010, our consultation led to the creation of the St. Kitts Foundation, a fund within The Ocean Foundation that dedicated 1% of gross sales from the South Peninsula Resort back into the community. On March 31, 2008, we completed our 18-month Phase One contract to design, create, and prepare the St. Kitts Foundation for full operations. This included the finalization of the formation of our St. Kitts Foundation as a charitable foundation under the law of the Federation.
Columbia's focus on outdoor conservation and education make them a leading innovator in outdoor apparel. This corporate partnership began in 2008, with a contribution to TOF's SeaGrass Grow Campaign, planting and restoring seagrass in Florida. For the past 6 years, Columbia has provided high quality in-kind gear that our projects rely on to perform field work critical to ocean conservation.
A foundation partnership was formed in 2010 to create the ISSF Sea Turtle Fund. This fund supports grassroots, science-based sea turtle conservation programs and emphasizes the critical need for social change for the recovery of a species. Together, we have raised over $306,000 to support protection of critical nesting sites for endangered Western Pacific Leatherbacks, recovery of foraging and nesting populations of the critically endangered Eastern Pacific Hawksbill, and reduce bycatch of turtles in Peru.
The Ocean Foundation partnered with jetBlue Airways in 2013 to focus on the long-term health of the Caribbean's oceans and beaches. This corporate partnership sought to determine the economic value of clean beaches to strengthen protection of destinations and ecosystems upon which travel and tourism depend. TOF provided expertise in environmental data collection while jetBlue provided their proprietary industry data. jetBlue named the concept "EcoEarnings: A Shore Thing" after their belief that business could be positively tied to shorelines.
The Ocean Foundation worked with Kerzner International in the design and creation of the Kerzner Marine Foundation, its grantmaking strategy and procedures, and in hiring their first CEO. The Blue Project, part of the Kerzner Marine Foundation, has provided over $1 million in grants to support marine science in the Bahamas.
The Ocean Foundation created a Resort Partnership Lasting Legacy Model, designing and consulting for the philanthropy arms of the sustainable resort developments in Loreto Bay, Mexico. Our resort partnership model provides a turn-key meaningful and measurable Community Relations platform for resorts. This public-private partnership provides a lasting environmental legacy for the local community for future generations.
The Ocean Foundation (TOF) served on the Environmental Program Advisory Group for the Margaret A. Cargill Foundation to design and develop its environment grantmaking program.


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Melted Metal, you know.
what can i say,perfect.
ficou muito bom, gostei das formas abstratas e das cores! parabéns
Great composition
Perfeito, conceito e concepção excelente, uma arte verdadeira e mereçedora de milhões de fav's
I love this kind of style of art. The colours and the simply yet intricate peices make it. Very nice.
uh.. wasn't this for oxy?
great colors, depth, and it's just impressive to have all that in vector form ;]
looks nice.
That looks great, and it does seem like metal melting..except for the gears or circles there..lol.
nice dont like the left but the right side is cool
got damn it looks like some wax melted!!
and you tell me its not hard. All Illustrator
God, I wanna learn to make this crazy 2d
muito boa essa eim mano. as cores tao muito boas
parabens vekin ;]
parabens vekin ;]
Excellent man, love the colors. Awesome job.
all illy?
essa paguei pau
achei bem tezão, curti as cores e as shapes
parabéns vekin
essa paguei pau
achei bem tezão, curti as cores e as shapes
parabéns vekin
Lovely stuff man
nice, but it looks like most sharpened.


text:
Just a quick update for everyone. I received confirmation last Friday that our excellent attorney's at DWT (http://www.dwt.com/) had filed our 1023 with the IRS. I will work on getting that up on the website shortly. Apparently the IRS still requires the 1023 to be filed via dead trees; the document is large and will need to be scanned.
The board has been busy prepping for the 1023 filing and part of that filing is to determine how we will be providing grants to members. This is the first run of how those grants will be allocated.
Grant types:
- There will be two types of grants:
- General grants - General grants are those that we don't plan for. It may be for a someone to give a talk at a show or to write a HOWTO.
In a recent post made to pgus-general [1], Josh Berkus makes an interesting point about the PgUS grant process. The PgUS grant process is currently designed in a way that restricts the benefits of the grants to PgUS members. It was designed like this on purpose (and currently being verified as acceptable via our attorney).
There are several reasons we decided to do it this way and here are my own (why I voted for it):
- PgUS is all about PostgreSQL in the U.S.
- Those who pay to participate should receive the benefits of the corporation first.
Just a small update, the bylaws [1] have been approved by the board. That was a major hurdle now crossed. Now our main focus is the 1023. The 1023 is the IRS form that allows us to claim 501c3 status.
The good news is, its mostly done. With the major outstanding issue being the process for applying for and receiving grants from PgUS. We will make sure and get that posted.
It has been a little quiet on the PgUS front of late but that doesn't mean work isn't happening. We have a new feature on the website that allows anyone to view resolutions that have been brought before the board. You can view those that have passed, failed or all at once. We have also received back what we hope is the last revision of the bylaws from our attorney. Lastly we have also determined our initial member benefits and dues.
Spoke with our Attorney today (Greg Hitchcock) he says, "I will try to get you a draft of the IRS application by the last week of April". We have already filed with the State of Oregon, this is the for the Federal 501c3 classification. This is great news because it means we could potentially be done with all of this before OSCON or LWE. At a maximum we will be done by West!


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Richard Nagle, the academy director for the state office of fire prevention, will portray Nick. Before becoming the academy director, Nagle was a lieutenant in the New York City Fire Department.
His former company, Engine Company 26, in the garment district of midtown Manhattan, lost its captain and four firefighters on Sept. 11, 2001.
"There was little I could do at the time, other than mourn their loss," Nagle said. "However, when Anne Nelson's play opened, I determined that by playing the captain, I could help to maintain the memory of those 343 brave men who were lost that day."
Nagle played the part of the captain on the second anniversary of the terrorist attacks at the Newman Theater, in Westchester County. Since then, he has recreated the role at the national fire academy, in Emmitsburg, Md., and the state fire academy, in Montour Falls. He has also performed the play for the Massachusetts Association of Fire Chiefs, the Virginia State Fire Chiefs Association and at the Consalati Theater, in Sheffied, Mass.
Playing Joan will be WNYT news anchor and health reporter Benita Zahn. In addition to covering health issues for the local NBC affiliate, she has performed many times in theater productions at the Albany civic theater, Schenectady civic theater, Schenectady light opera, and the Park Playhouse.
The show will be performed at 7:30 p.m., Sept. 11, at the Capital Repertory Theatre, 111 N. Pearl St., Albany. Tickets are available on a first-come, first-served basis for $10.
Firefighters and Capital Rep donors of $100 or more receive free admission. Seats are available by calling the box office at 445-7469.""
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Towards the unknown. by MarioGutiWatch
©2013-2016 MarioGuti
Vega de Pas, Cantabria, Spain.
awesome mountains
Interesting to see half the road covered by earth! Makes for a very interesting drive I would venture. Great shot!
I don't think half pf the road is covered. It is just a very narrow road (I think).
Great shot anyways!
Great shot anyways!
Wow, very narrow. Yes, it is a great shot!
We have roads like that here in norway too. Glad I don't need (and can't ) drive Thanks for the watch by the way.
True guys, it's a really narrow road crossing a mountains range (you couldn't cross all of it now because of the snow though), not half of it eaten by the Earth But it's a huge pleasure driving over here, no cars, nice curves...it's like being a participant of a rally. Plus I had to go a bit fast because it started snowing and I had no chains to put in my wheels!
You're very welcome


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Howard Tupper
Village Party
Baldwinsville resident since 1941
Political experience:
Trustee since 1995
Village representative for Canton Woods Senior Center for four years
Member of the department of public works, labor relations and tree committees, NW Human Services and inter-municipal consortium
Community involvement:
American Legion, Beauchamp Historical Club, McHarries Legacy and CNY Waterways association
Military experience:
Honorable discharge, US Army as a Spec/5 during the Vietnam era.
How do you envision Baldwinsville's future?
Let's be realistic. We have built a tremendous momentum for economic development in the past decade through careful planning and direct village action. None of this happened by itself. I'm a capitalist, not a utopian, so I believe private investment is the key to long term future success. We have a couple of very important specific projects to resolve -- Harrington Firehouse and the DPW facility on Lock Street. We should be open to the creativity of the private sector. The public interest will be taken care of by planning board oversight using bold new tools such as overlay districts and other zoning regulations, as well as the EDR consultant's report as a guide. It is a dynamic, evolutionary process that builds on itself, and any changes in our form of government should only enhance those capabilities.
Increasing property taxes and the current effort to consolidate seem to be two issues at the forefront. What is your take on these issues?
Consolidation is only one of the means that should be looked at to save taxes. It is not an end in itself. An easy target for consolidation would be the parks and recreation departments, since the village does not have a recreation staff, but our residents pay for town departments through whole-town taxes. A combined department would have a lot more real estate and a smaller administration.
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Is your favorite show in top? Which comedies are soaring, and which dramas are tanking? Did anyone watch that over-hyped new reality show? Keep up with the Nielsens here. The ratings system is complicated; we understand it so you don't have to.
TV Ratings: 2015 Academy Awards numbers appear to be down
Type: Post | Date: Monday, Feb 23, 2015Overnight time period data is off double-digits from last year
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Type: Post | Date: Thursday, Oct 30, 2014Final numbers won't be in until later, but America loved Madison Bumgarner
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Type: Post | Date: Monday, Oct 27, 2014On a night with two NFL games and a World Series matchup, the Peacock appears to have the edge
Tuesday Ratings: 'Hollywood Game Night' return caps NBC win, 'Zoo' is steady
Type: Post | Date: Wednesday, Jul 8, 2015'America's Got Talent' leads Tuesday in all measures
Sunday Ratings: How many people watched Team USA's World Cup win?
Type: Post | Date: Monday, Jul 6, 2015'Big Brother' and 'Celebrity Family Feud' still draw on Sunday
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Type: Post | Date: Thursday, Oct 16, 2014'Black-ish' viewing continues to fluctuate
Wednesday Ratings: 'Celebrity Wife Swap' tops 'Extant' among young viewers
Type: Post | Date: Thursday, Jul 2, 2015'MasterChef' helps FOX also tie for the key demo lead
TV Ratings: NBC wins Monday, 'Jane the Virgin' debuts well for CW
Type: Post | Date: Tuesday, Oct 14, 2014No big drops, with 'Scorpion' and 'Gotham' stabilizing
TV Ratings: Super Bowl XLIX eyes new record in early figures
Type: Post | Date: Monday, Feb 2, 2015Patriots-Seahawks thriller will likely be the most watched program in TV history
Thursday Ratings: Viewers orbit 'Astronaut Wives Club' premiere but CBS leads
Type: Post | Date: Friday, Jun 19, 2015'Big Bang Theory' repeat is Thursday's top show in most measures


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University of Redlands > Prospective Students >
International Students >
Undergraduate International Students >
Adult and Working Professionals >
Advisors & Assistance
International Student Services
University of Redlands welcomes students from more than 23 nations. These students are supported by the International Student Analyst. Services include orientation for new students, information and assistance on visa, employment, change of status, reinstatement issues and advising.
Contact Information:
Miral Charabi
International Student Analyst
(909) 748-8716
Our office is in the Campus Diversity and Inclusion Office located in the Hunsaker Center.
Office of Admissions
For assistance with the admissions or application process, please contact our International Admissions Advisor
In April 2010, it was designated a Tree Campus USA by the Arbor Day Foundation. Redlands is among just three other colleges or universities in California to receive this designation.
© 2015 University of Redlands. All Rights Reserved.


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text: STEM education Manor New Tech High School Takes Project-Based Learning to Thailand By Syeda Hasan • Nov 19, 2013 twitter.com/ManorNewTech For students at Manor New Technology High School, lectures and homework assignments are a foreign concept. Tablets take the place of textbooks, and many classes are taught by a team of instructors. This fall, a group of students is working to bring their school's innovative learning system abroad. The school exclusively utilizes project-based learning, a process that teaches course concepts through hands-on projects and presentations which students design themselves. Steve Zipkes, Manor New Tech's principal, says it's a more engaging and up-to-date learning system. "Student these days are digital natives," Zipkes says. "We're using technology as the invisible tool. It's not what makes teaching and learning, but it certainly enhances it. With our students today, it's almost a necessity." Report: More than 1 in 5 Austin Area Jobs Require STEM Skills By Laura Rice • Jun 10, 2013 Caleb Bryant Miller for KUT News More than 22 percent of Austin area jobs require specialized STEM skills. STEM stands for Science, Technology, Engineering and Math. A study released by the Brookings Institution today shows Austin's percentage of STEM jobs in 2011 was slightly higher than the national average of 20 percent. As Obama's High School Visit Nears, Education Advocates Question Emphasis on STEM By Kate McGee • May 9, 2013 flickr.com/amylovesyah Listen Listening... / 3:27 Story as it aired on KUT News 90.5 FM President Obama is visiting Manor New Tech High School, which has a STEM-based education program. But some experts question is there's too much emphasis on STEM. Brenda Ramlow's daughter Paige is a junior at Manor New Tech, the high school President Barack Obama is visiting this afternoon. She says her daughter is interested in a career in video graphics.


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Litinterp Guesthouse Vilnius Reviews
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The location was probably the best part - right in the centre of the old town. The room is fairly basic but it has everything you need. I really appreciated being given a shampoo sachet and having a hairdryer to use after staying in hostels before! For the price it's really great... but if you are looking to meet people or have any interaction it's no good for that.
- Novice Nomad
- Anonymous
- England
- Female, 18-24
- (2 reviews)
we stayed only for the week-end and tis hostel is a very good place to put our stuff and to sleep. It is very quiet!
- Novice Nomad
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- France
- Female, 31-40
- (1 review)
The location is perfect; in the heart of Vilnius. I would say such a warm welcome that I received the first time I entered the hostel. The building is quite old of which it adds unique value of the hostel. Model of the room is like in flat, one room in one flat. Tidy and clean :) Finally, I must not forget the impression that the owner made. The owner (I think) mentioned how I was the first person from my country, Indonesia who has ever stayed in the place. What a delightful welcome, indeed.
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To be violent to everyone in sight ._.
Best Answer
An urge pushed to its limit is an urge towards death
Best Answer
An urge pushed to its limit is an urge towards death
Best Answer
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Music Recorder 14.0.56300
Instantly stream your favorite songs and music videos. Automatically record albums or entire discographies from over 100,000 radio stations as free MP3s. Discover new artists with similar music and complement your music library. Automatically generate playlists and copy your favorite music to your smartphone or burn an audio CD.
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Zulu DJ Software Free 3.66
Zulu DJ software is the complete DJ solution. An easy-to-use interface makes mixing your favorite tracks easy. Apply effects on the fly while mixing your favorite music. Zulu DJ supports all of the latest audio file formats so playing and mixing your favorite songs is simple and fun. Automatic beat detection ensures that your tracks will be perfectly synced.
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Crescendo Music Notation Editor Free 1.66
Crescendo Free Music Notation Editing Software is perfect for composing original songs, music, scores, and soundtracks. The program features a wide variety of text, key signatures, time signatures, and notation symbols all on a free-form layout to give you complete control over your music creation. With Crescendo you can compose music for film, a band, a score, or just for fun!
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Aiseesoft FoneTrans 8.2.12
Aiseesoft FoneTrans is the first-granted iPhone Transfer software, which does well in file transfer between iOS devices and computer. It can transfer video, music, photo and many other multimedia files from computer to iOS device, including iPhone 6s/6s Plus/6/6 Plus, iPad mini 4, iPad pro, etc. Even if the video/audio files are incompatible with your devices, FoneTrans can convert these video/audio files automatically before transferring. In addition, it enables you to backup Contacts and SMS to your computer and make files transfer between any iOS devices. Key Features 1. Transfer file between iOS device and PC FoneTrans can help you import video, music, photo and other media files from computer to iPhone/iPad/iPod for enjoyment anywhere and anytime. It also allows you to export files from iOS devices to computer/iTunes for backup. 2. Share files between iPhone/iPod/iPad Apart from transferring files between computer and iOS devices, you are enabled to transfer files between any iOS devices for f ...
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Happy Photo Viewer 1.0
View your photos on screen with the information when and where the photos were taken. Simply point to the folder of the photos, and enjoy a dynamic slideshow with 256 transition effects, which can be random, fixed, or sequential. It's up to you to decide how fast your photos are displayed in the slideshow, and how your photos are fit to screen. You can create your customized playlist to play only your preferred songs as the background music.
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Guitar Chords Library 5.1
Guitar Chords Library. Novel tool for people who want to learn to play guitar. With this program you can create sheets based on your favorite songs and melodies. Store and unpack the collections at will. The program visually displays and stores tabulations which can be used by a novice. Beginners can learn to play chords and melodies. This full version supports Russian and the English languages, no registration required!
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Power Music Essentials 126.96.36.199
Management and software for musicians - display music on screen like a digital music stand. No more paper, fast search of your songs and instant display. Create playlists (set lists). Powerful chord sheet editor. Transpose chords. Scan music directly into the software or import from PDF. Multiple page per screen display, easy page turning with one tap or use a foot pedal.
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Xnotika Player 184.108.40.206
Listen for free Italian rock songs with an innovative player software. Xnotika player is a unique audio software that embodies a real musical disc with an introspective and sharp taste. Realized from the namesake Italian rock band, the Software contains less than 5 songs to enjoy for free including text , photos and information , links to the Rock Band Official Website and a specific section for donations to the musical project.
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Virtual Drum And Piano 3.6
Behold out new Virtual Drum And Piano simulator. You don't have the instruments or means to buy them? Then Virtual Drum And Piano is just for you. You can produce REAL MUSIC on the drums, songs played with real rhythm and inspiration. Add in some piano to brighten the mood. Controls are simple using the keyboard and mouse. Feel good about what you are playing with this software and maybe even produce a hit song!
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Seascape 3D Screensaver 1.01.5
This screensaver conveys the whole atmosphere of the seaside with the murmur of the ocean, the cries of seagulls and the songs of the wind. Listen to these calming sounds and watch the eye-pleasing scenery! Forget about all you problems and dive into this world of relaxation and meditation.
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AnyMP4 iPhone Transfer Pro for Mac 8.3.62
AnyMP4 iPhone Transfer Pro for Mac enables you to transfer photos, video, music and many other multimedia files from iPhone/iPad/iPod such as iPhone 6s/6s Plus, iPhone 6/6 Plus, iPhone 5s/5c, iPad Air, iPad pro, iPad mini 4 and iPod, etc to Mac for backup. It also allows you to import Mac/iTunes files to iPhone/iPad/iPod. It can also convert the incompatible video/audio to iPhone/iPad/iPod supported format. Key Features 1. Transfer files from iPhone/ iPad/ iPod to Mac This iPhone to Mac Transfer can help you transfer photo, video, music and other media files from iPhone 6s/6s Plus, iPhone 6/6 Plus/ 5s/5c, iPad pro, iPad mini 4/3/2, iPod and more digital devices to Mac/iTunes for backup. 2. Import files from Mac to iPhone/ iPad/ iPod With this Mac to iPhone Transfer, you can convert photo, video, music and others to iPhone/iPad/iPod. As for the unsupported video/audio files, this software will convert them into compatible formats before transferring. 3. Transfer files between iPhone/ iPad/ iPod ...
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Replay Music 7.1
Replay Music is the best streaming audio recorder available. It records streaming music online from any music site or streaming service (Spotify, Pandora, and more) without capturing system sounds, giving you a clean recording. Plus, find any song with the built-in Media Guide. Save your recorded songs as MP3, FLAC, OGG, WMA, M4A or WAV, perfectly separated into individual tracks & correctly tagged.
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AV Voice Changer Software 7.0.62
Change your voice over IP and PC to phone; change voice's gender and age to have fun in online voice chat; create different voices for dubbing; morph songs and voices in songs; record voice chat, phone conversation, Internet radio, and music from online sites; add audio and background; compare changed voice to another's voice for simulation purposes; compatible with most instant messengers, PC to phone clients, game servers, and media players.
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Song Sergeant 1.7
Song Sergeant intelligently identifies and removes duplicates, renames inconsistently named artists and albums, reunites orphaned song files to your library, and deals with missing song files. • Finds and removes duplicate song files • Intelligently merges the best song information with the best audio data • Preserves your playlists while removing duplicates • Identifies inconsistently named artists and albums • Discovers orphaned song files within your music folder but not seen in iTunes • Reunites missing library songs with orphaned files • Fix problems quickly and automatically or with great manual control • Detailed 'related songs' section helps you make decisions
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FreeGamia Mus Rif 1.0
Music Riffter is a new and easy system to create your own musical compositions. Have you always wanted to make music, but don't have the time or money? Problem solved! With Music Riffter you can create songs without leaving your home with its huge number of tools. This program is for people who do not know anything about music and also for professional musicians. No strings or keys, just buttons that create a melody. Enjoy the simple interface an
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FreeGamia Virtual Drum And Piano 1.0
Behold out new Virtual Drum And Piano simulator. You don't have the instruments or means to buy them? Then Virtual Drum And Piano is just for you. You can produce REAL MUSIC on the drums, songs played with real rhythm and inspiration. Add in some piano to brighten the mood. Controls are simple using the keyboard and mouse. Feel good about what you are playing with this software and maybe even produce a hit song!
Download now
FreeGamia Guitar Chords Library 1.0
Guitar Chords Library. Novel tool for people who want to learn to play guitar. With this program you can create sheets based on your favorite songs and melodies. Store and unpack the collections at will. The program visually displays and stores tabulations which can be used by a novice. Beginners can learn to play chords and melodies. This full version supports Russian and the English languages, no registration required!
Download now
Mus Rif 1.8
Music Riffter is a new and easy system to create your own musical compositions. Have you always wanted to make music, but don't have the time or money? Problem solved! With Music Riffter you can create songs without leaving your home with its huge number of tools. This program is for people who do not know anything about music and also for professional musicians. No strings or keys, just buttons that create a melody. Enjoy the simple interface an
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MelodyBuilder 6
Create awesome chord progressions and melodies MelodyBuilder allows you to quickly try out chord progressions, experiment with new song ideas, create arpeggios and melodies, even if you don't know much about music theory. Everything you create in MelodyBuilder can be exported to midi files and imported in your songs in your favourite sequencer software.
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Video Screensaver 1.0
Put your favorite videos/mp3 songs as screensaver. This software plays videos/mp3 songs as screensaver. It supports hotkeys for all operations. It can be protected by password. Once activated it can be closed only if correct password is entered. It contains a play list and database in which multiple videos/mp3 songs can be loaded and stored. Videos and mp3 songs in the play list can be either played randomly or in a sequence .
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Sofonica Shutdown Timer 1.0
Free Shutdown timer is the software which can automate Shutdown,restart,log off,lock,Hibernate and Standby operations.This can be very helpful if some activity is being performed on your system and you want to shut down pc after a time period.This helps in saving electricity bills.If you are habituated of listening to songs while sleeping,this software can help you.Start a song and set the interval after which shutdown should be automated.
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Broadcast Equalizer Limiter 2015
When Auto Correct is enabled, it will scan all selected frequencies in the WAV file to determine the minimum and maximum amplitudes. It will then correct these variations by automatically increasing or decreasing the levels of attenuation at specific frequency intervals (usually 1/3 octave). The result is a nearly linear frequency response. For the listener, this creates more consistent sounding audio. A typical application that would benefit from this tool is an internet radio station. A common problem that many of these stations experience is an inconsistency in true audio reproduction (i.e., different songs sound different). By utilizing this function, one may be assured that there will be an average and consistent degree of bass and treble response, independent of a specific song title or artist.
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KaraokeMedia Home 18.104.22.168
Full player all in one, audio and video, specially dedicated to karaoke. Plays all video and audio formats includes KM3. Key Change. Record your song in audio. Record you songs in video. Karaokemedia Store: similar to itunes but in karaoke. Sound Effects. Complete Song List. Playlist. Favorite Songs. Complete Information of songs. Grafic Equalizer 10 bands. Complete Stats. Include Several Songs in new km3 format.
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Karaokemedia Home 3 184.108.40.206
Full player all in one, audio and video, specially dedicated to karaoke. -Plays all video and audio formats such as: MPG1, MPG2, MPG4, AVI, Divx, Vob, Cdg, Mp3+g, WMV, WMA, WMA+G, MP3, ASF, Midi, Ogg, MOV, MP4, Aac, SWF, FLV. The new format also reproduces KARAOKE KM3 It has all the important functions karaoke: -KEY CHANGE -5/0/+5. To adapt the music to your voice. -MULTIPLEX Void voice in the karaoke tracks with voice track. -RECORD YOUR SONGS IN AUDIO. Edit and prepare your recordings with your voice. -RECORD YOUR SONG IN VIDEO. With your image and your webcam -SHARE YOUR VIDEOS. Upload your recordings to the Internet directly. -COMPLETE SONG LIST , By artist, by title,number,style, format, and export to PDF, Word, excel, html, bmp, jpg etc. -KARAOKEMEDIA STORE: Buy your songs karaoke in KM3 format, Playbacks or Wmw with a single click, and you'll be singing it in 5 seconds. Is similar to itunes but in karaoke. -PLAYLIST, choose your songs, take the microph ...
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Radiola 2.0.1
Radiola is a reliable software that enables you to listen to online radio stations, right from your desktop. The software features a list of musical genres and offers you several radio stations that play your favorite type of music. It can display a history of rendered songs and supports adding extra playlists from local files. Listen to online radio with one mouse click
Download now
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Round-Up - The End of Fortune Brands?
Fortune Brands has confirmed today (8 December) that it will split its three businesses but hold on to Beam Global Spirits & Wine. just-drinks' coverage of the situation is all here.
US: Diageo and Bacardi to team up for Beam Global? 17 Dec 2010
Bacardi could emerge as the supporting actor for Diageo's tilt at Beam Global Spirits & Wine, according drinks analysts.
In the Spotlight - A Fortune in three independent divisions? 10 Dec 2010
Fortune Brand's decision to split into three independent businesses is the first step to unlocking the full value of the firm's portfolio, however it seems investors may need patience if they are to understand the true value of the separation, analysts wrote this week.
Comment - Can Fortune Brands hold its drink? 9 Dec 2010
The writing has been on the walls of Fortune Brands' offices in Illinois for about two months. The conglomerate's confirmation yesterday that it will split up its three business units was clear to see back in October, when hedge fund firm Pershing Square Capital Management announced it had upped its stake in Fortune to 11%. Considering Pershing's previous history of pushing companies to sell off corporate divisions, one can understand that the countdown on Fortune began very soon after Pershing's announcement.
just the Facts - Beam Global Wine & Spirits 8 Dec 2010
Fortune Brands this morning (8 December) confirmed that it will break up its three business units and will look to become "focused solely" on its Beam Global Spirits & Wine division. Here just-drinks takes a closer look at the firm's wine and spirits division.
US: Fortune Brands separates units, holds on to Beam Global 8 Dec 2010
Fortune Brands has confirmed that it will break up its three business units and will look to become "focused solely" on its Beam Global Spirits & Wine division.
Update - US: Fortune Brands silent on break-up talks 15 Nov 2010
Fortune Brands has declined to comment on whether it has held talks with activist shareholder Bill Ackman on splitting and selling the group's spirits, golf and home businesses.
US: Fortune Brands facing break-up - report 15 Nov 2010
The owner of Beam Global Spirits & Wine, Fortune Brands, is facing pressure from an activist shareholder to split and sell its drinks, golf and home businesses, according to a report.
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The Red Sox walked off with a victory over the Mariners in the 15th inning on July 31. Before doing so, Jonny Gomes completed a sensational — and very unique — double play to squash a Seattle rally.
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