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The long lifespan and low turnover of human islet beta cells estimated by mathematical modelling of lipofuscin accumulation
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Defects in pancreatic beta cell turnover are implicated in the pathogenesis of type 2 diabetes by genetic markers for diabetes. Decreased beta cell neogenesis could contribute to diabetes. The longevity and turnover of human beta cells is unknown; in rodents <1 year old, a half-life of 30 days is estimated. Intracellular lipofuscin body (LB) accumulation is a hallmark of ageing in neurons. To estimate the lifespan of human beta cells, we measured beta cell LB accumulation in individuals aged 1–81 years.
LB content was determined by electron microscopical morphometry in sections of beta cells from human (non-diabetic, n = 45; type 2 diabetic, n = 10) and non-human primates (n = 10; 5–30 years) and from 15 mice aged 10–99 weeks. Total cellular LB content was estimated by three-dimensional (3D) mathematical modelling.
LB area proportion was significantly correlated with age in human and non-human primates. The proportion of human LB-positive beta cells was significantly related to age, with no apparent differences in type 2 diabetes or obesity. LB content was low in human insulinomas (n = 5) and alpha cells and in mouse beta cells (LB content in mouse <10% human). Using 3D electron microscopy and 3D mathematical modelling, the LB-positive human beta cells (representing aged cells) increased from ≥90% (<10 years) to ≥97% (>20 years) and remained constant thereafter.
Human beta cells, unlike those of young rodents, are long-lived. LB proportions in type 2 diabetes and obesity suggest that little adaptive change occurs in the adult human beta cell population, which is largely established by age 20 years.
KeywordsAgeing Human Islet Longevity Mathematical modelling Monkey Mouse Neogenesis Pancreatic beta cell Type 2 diabetes
Electron microscopy
Lipofuscin body
The aetiology of type 2 diabetes includes both genetic and environmental factors that affect the production of insulin from pancreatic islet beta cells and the sensitivity of peripheral tissues to insulin. Many of the new genetic markers for type 2 diabetes implicate aberrant development or production of beta cells in utero or in later life, or are associated with cell turnover/regeneration [1, 2, 3]. It has been hypothesised that the beta cell population flexibly adapts to insulin requirements and is normally determined by an equilibrium of apoptosis and neogenesis and/or replication of beta cells [4, 5, 6, 7]. This recent concept of islet cell plasticity replaces the long-held view that cell number is largely established during embryogenesis and early life and remains relatively unchanged thereafter. Increased demand for insulin with increased insulin resistance/obesity would lead to a larger beta cell population; failure to expand beta cell number by replication and neogenesis and/or increased apoptosis would result in type 2 diabetes [8, 9]. An increase in the beta cell population with increased demand for insulin in obesity is very evident in rodents [10] but is smaller and variable in obese humans [11, 12]. The half-life of beta cells has been estimated to be 30–60 days in young rodents (<1 year old) on the basis of histological quantification of apoptotic and neogenic cells [9]. Using similar techniques, replication of human adult beta cells has been estimated to be tenfold less than that in adult mice [4, 11] and to be highest in children <5 years old [13]. Incorporation of BrdU into mouse islet cells decreases with age and becomes very low in animals at age 1 year [14], suggesting that the beta cell population becomes largely post-mitotic by 12 months. Nevertheless, extrapolation of cellular turnover and neogenesis in relation to onset of type 2 diabetes continues to be based on young mouse models [15].
Insulin secretion in non-diabetic humans decreases with age in vivo [16]. Ageing of tissues involves insulin/IGF-I signalling [17], and the 'free radical theory of ageing' [18] is supported by evidence of an age-related decrease in mitochondrial function [19]. Understanding the ageing of beta cells, which are highly dependent on ATP production for insulin secretion, is therefore of importance.
Few methods exist to determine the lifespan of cells. Telomere length is a marker for the number of cell divisions and is shorter in proliferative cells [20] compared with those of the brain, liver, kidney and heart, which are considered to be post-mitotic [21]. Recent innovative experiments to determine cell age by radiocarbon dating indicate that cortical neuronal life equals the life of the individual but intestinal cells are younger [22]. Lipofuscin bodies (LBs) are storage organelles of the lysosomal system and their accumulation in the cell is a feature of ageing in post-mitotic cells in mammalian and other species, particularly in neurons [23] and cardiac myocytes [24, 25]. An increase of 'lipid-storing vesicles' in beta cells with age has been described [26] but these were not identified as lipofuscin. The aims of this study were to determine if lipofuscin accumulation in human and non-human primate beta cells and other pancreatic cell types is age-related and could be used as a marker for longevity. These data were compared with that of aged mice. Using mathematical simulations we modelled the accumulation of LB in three dimensions (3D) and estimated the degree of ageing vs neogenesis and replication of beta cells over a wide age range in humans. The modelling was evaluated by quantitative volumetric morphometry of 3D electron microscopy (EM) of a human islet.
Human pancreatic tissue
Human pancreatic tissue was obtained from the pancreatic islet donor programmes centred in Leiden and Brussels and from the Islet Transplant Unit in Oxford. Protocols were approved by Local and Regional Ethics Committees in Holland, Belgium and the UK. Human islets were prepared by collagenase digestion. Islet tissue was obtained from individuals aged 1–81 years (n = 55). Donor BMI was known for 36 samples (mean 25.6 ± 0.9 [SE] kg/m2; range 16–36 kg/m2). Cause of death of the donors was trauma or cardiovascular disease and 45 donors had no history of diabetes; ten had documented evidence for type 2 diabetes. This large cohort includes data from 11 non-diabetic patients originating from the Brussels' cohort, which has been reported previously [26]. Human, non-malignant insulinoma specimens were obtained from surgical resections in Oxford and Brussels with permission from the Local Ethical Committees and the patients (individuals aged 32–79 years, n = 5).
Non-human primate pancreatic tissue
Non-human primate pancreatic tissue was resected immediately post-mortem from macaque monkeys; animals aged 5–30 years had been bred and maintained in captivity according to US animal regulations, and the Institutional Animal Care and Use Committees.
Mouse islets
Pancreatic tissue was prepared for EM from C57BL/6 mice aged 10–99 weeks (n = 15). Animal care conformed to the UK and Belgian regulations for care of laboratory animals and investigations conformed to the Guide for the Care and Use of Laboratory Animals published by the US National Institutes of Health (NIH publications No. 85-23, revised 1985). Mouse islets and tissue was processed for EM as described for human samples.
Electron microscopy
Islet and pancreatic tissue was fixed in either 4.5% glutaraldehyde (wt/vol.) in cacodylate buffer (pH 7.3) or in 2.5% glutaraldehyde in phosphate buffer (pH 7.2), post-fixed in osmium tetroxide (1% wt/vol.) and embedded in Spurr's resin (Agar Scientific, Stansted, UK). Some specimens were embedded in LRGold resin (Agar Scientific) for immunolabelling for transmission EM. Acid phosphatase was localised using a modified Gomori reaction, as previously described [26]. Ultrathin sections were cut onto nickel grids and contrast enhanced with uranyl acetate and lead citrate. Immunogold localisation of the lysosomal enzyme cathepsin D was made using antibodies raised in rabbits (1:5,000) (DAKO, High Wycombe, UK) and Protein A gold 15 nm (Biocell, Cardiff, UK).
Quantification of LBs was made on EM images of 20–50 beta cells per specimen independently in Brussels and Oxford; in embedded pancreatic specimens beta cells were selected at random from cross-sections of at least two or three different islets having the typical islet structure of the 'dorsal pancreas' with very few cells containing pancreatic polypeptide. Thirty-five samples collected for EM in Brussels consisted of 100,000 dispersed islet cells obtained following islet isolation. Therefore, in these samples cells were derived from far more than two or three islets. LBs were defined as multivesicular structures, bounded by a membrane and containing both electron-lucent (lipid-like material) and a more electron-dense (pigmented) rim. Smaller (<6 mm diameter) secondary lysosomes containing homogeneous electron-dense material were not included in the analyses. The cross-sectional areas of the LBs were expressed in relation to the measured area of the cell cytoplasm and the number and size of LBs recorded for each cell.
Validation of the sampling of islet cells for LB content was done by assessing the reproducibility of the measurements in different batches of islet cells that were maintained in vitro for 2–8 days or for 10 weeks in vivo in a model of transplantation in nude mice (see Electronic Supplementary Material [ESM] for methods). For the alpha and beta cells, 60% of replicate measures had a CV < 10% and 90% had a CV < 20% (ESM Fig. 1). These data suggest that the method is robust and reproducible.
For 3D EM, fixed and osmicated islets from a human donor (aged 40 years) were embedded in Spurr's resin and prepared for serial sectioning and 3D imaging by scanning EM [27] (see ESM for methods).
Statistical analyses
Statistical associations were made using linear or logarithmic regression (loge) (correlation coefficient r). Multiple regression analysis was used to examine the association between accumulation of LBs (dependent variable) and age, BMI, sex or diabetes (independent variables).
Modelling the number and size of LBs in the beta cell
Probability theory and mathematical formulas do not allow derivation of information in 3D from a two-dimensional (2D) picture. We therefore estimated the proportion of lipofuscin-containing beta cells and the number and size of LBs in 3D and their distribution throughout the cell by building a simplified 3D model in the program Mathematica (ESM Model 1 and Simulations 1–3). The programming characteristics of Mathematica allow rapid generation of a very large number of simulations, thus yielding high statistical confidence. These data were compared with micrographic images and morphometric data obtained from patients of different age categories. The input variables were adjusted until the output data fitted with the morphometric data. Volumetric data from the 3D EM analysis were compared with data predicted by mathematical modelling for that age.
LB content of beta cells increases with age
LB area proportion in mouse beta cells was low (<0.4%) (ten times less than that in human beta cells) and stable in animals <1 year old, but there was an increase in content in mice >1 year old (Fig. 3b; r = 0.77, p < 0.001). The proportion of LB-positive cells increased with age in mice, reaching a maximum of 65% (aged >1 year) (Fig. 3c; r = 0.50, p = 0.055).
The number of LBs per cell section also increased with age in both human (Fig. 2d) and non-human primates. These variables were not apparently different in the type 2 diabetic patients (aged 29–75 years) compared with non-diabetic participants (Fig. 2). When analysed separately, LB area proportion from the ten type 2 diabetic patients was also correlated with age (r = 0.64, p = 0.04). There was no relationship of sex (data not shown) or BMI to LB area proportion or LB-positive cell proportion by linear regression (ESM Fig. 3). Using age and BMI as independent variables in a multiple regression model, age was strongly correlated with LB number, LB area proportion or LB-positivity (standardised coefficients 0.74–0.85, p < 0.0001) but BMI was not (coefficients 0.07–0.12, p > 0.3). Similarly, in a multiple-regression model with age, BMI, sex and diabetic status as independent variables, LB content was correlated with age (standardised coefficients 0.74–0.85, p < 0.0001), while none of the other variables showed significant association (with standardised coefficients for diabetic status 0.02–0.08, p > 0.5).
In human insulinoma cells, both LB area proportion and percentage of LB-positive cell sections were clearly different from that in human beta cells of donors at equivalent ages (Fig. 2a, c). The area proportion in insulinoma cells was low (<2%) at all ages of patients examined (32–79 years at surgery). At aged 80, the area proportion was 1% in insulinoma cells compared with 14% in normal beta cells, and the fraction of LB-positive cell sections was 31% in insulinoma compared with 94% in normal beta cells. In one patient (aged 47), both tumour and pancreatic islet cells were examined and the LB area proportion in insulinoma cells was 40% of that found in beta cells.
The LB population distribution changed in beta cells with ageing (ESM Fig. 4a, b). The likelihood of detecting a human beta cell with few and small LBs in the section became low after the second decade; in insulinoma cells both LB area proportion and percentage of LB-positive cell sections were clearly different from those in beta cells of donors at equivalent ages and resembled more closely those of donors <10 years old (Fig. 2a, c; ESM Fig. 4).
Mathematical modelling demonstrated that the beta cell population is established by age 20
The modelled data corresponded well with the observed logarithmic increase in the percentage of LB-positive human beta cell sections per age category (Fig. 5c, d); the number of LBs per cell section (2D) increased progressively with age from 0.2 to 5 (Fig. 5f). This fitted with the measured data, which were more variable (Figs. 2d and 5e). According to the model, the total number of LBs per cell in 3D does not increase very much with age, from ten per cell at young ages to about 25 per cell in the older age groups (ESM Table 1); the increased probability of sectioning lipofuscin results largely from the increased size of the bodies. The model showed that the percentage of beta cells containing LBs in 3D is 89% at aged 1 year, 95% at 5 years, 97% from 20 years on and 98% after 50 (Fig. 5d). This suggests that a very high proportion of beta cells are long-lived even in teenagers and young adults.
Preliminary 3D modelling of the data from five older mice where the LBs were larger and more numerous demonstrated that after 12 months, a mouse beta cell contains approximately seven LBs (compared with 25 in human beta cells after age 50 years and between two and four in human insulinomas). These LBs occupy 2–4% of the cytoplasmic volume of a mouse beta cell (compared with 20% in human beta cells and 0.5–4% in insulinomas).
Validation of the mathematical model from 3D EM
Comparisons were made of the mathematical predictions and area and volume proportion derived from the 3D EM. LB area proportion (in 2D) was estimated by automatic imaging in scanned serial images. LB area proportion was 5.5%, and LB volume proportion was 9.4% in a specimen from a 40-year-old individual. These 3D imaging data are very similar to the values for this age predicted by mathematical modelling (Fig. 5 and ESM Table 1).
Estimation of LB-positive cell proportion in 3D was made using the images in Fig. 4c. These images represent a traverse of ~50% of a beta cell diameter (8 μm) and demonstrate that measurements made from a single cell section underestimate LB content. In one section (Fig. 4c), 42% of cells were LB-positive. However, LBs could be identified in the other cells in consecutive images (Fig. 4d–j), resulting in a total LB-positive cell proportion of 98%, which is directly comparable to the mathematical prediction (Fig. 5).
The positive linear correlation between age and the LB area proportion in human and non-human primate beta cells is similar to data derived from LB distribution in post-mitotic cells in other organs such as the human brain [23, 29, 30] and rat cardiac myocytes and neurons [24, 31, 32] and extends the observations made previously on 'lipid-storing vesicles' [26]. Lipofuscin is similar in appearance to ceroid, which accumulates rapidly as a result of pathological conditions such as neurodegenerative and genetic diseases but is not age-related [33]. LBs in beta cells were immunopositive for the lysosomal proteases cathepsins B and D, indicating their relationship with the lysosomal system. Lipofuscin represents the end stage of intracellular lysosomal degradation; senescent or damaged mitochondria, membranes and secretory granules are incorporated into lysosomes by autophagy [34, 35], but increased peroxidation and cross-linking renders lipids and proteins in the lysosomes resistant to lipases and proteases. This results in formation of LBs as waste-storage organelles [34], which, in many non-proliferating cell types, cannot be exported. Lipofuscin content was low and unrelated to age in the proliferating human insulinoma cells, demonstrating continuous dilution of LBs into daughter cells, and a short age-span of these cells. Our data from primate beta cells suggest that, like cardiac and skeletal muscle and neurons, human islet beta cells are post-mitotic and have a very long lifespan. Alpha cells and non-granulated ductal cells also exhibited an age-related increase in LB population. However, the rate of accumulation was lower. The LB proportion in mouse beta cells, even at ages >12 months, was very low (one-tenth of that found in primate cells). It remains to be conclusively determined whether this is merely because of the different lifespans of the mouse and man, or whether beta cells in the two species have different intrinsic characteristics contributing to LB formation and accumulation, with cell replication and neogenesis counteracting the latter.
The low proportion of human beta cells containing no LBs, implying a short life history (11% at aged 1 year, 5% at 5 years and 2–3% in adult life), suggests that neogenesis or transdifferentiation of beta cells from ductal or other precursors is uncommon in normal, obese and type 2 diabetic human pancreas. Dividing beta cells are most numerous in children <5 years of age [13]. Our data on longevity are derived from viable cells in human islets in situ in the pancreas or in vitro following islet isolation; apoptotic or damaged cells were not included in our analyses and no marker for cell division was available for use with EM. Thus, information relating to cell death cannot be derived. The higher rate of LB accumulation with age in beta cells compared with alpha cells in the same individual could represent differences in cell turnover or result from different degrees of lipid uptake [26, 36], mitochondrial turnover or disposal of autophagic lysosomal material in the two cell types [30]. The number and size of LBs in murine beta cells at 12 months old was substantially lower than those of beta cells of humans aged 50 years; this would be consistent with a lower proliferation rate in humans compared with that in mice <12 months old [37, 38, 39]. Evidence for a post-mitotic and non-regenerative population of adult human beta cells is provided from observations that human beta cells are resistant to proliferation in vitro compared with rodent cells under the same conditions [38]. Furthermore, there was no evidence for islet neogenesis in man following partial pancreatectomy [40], in contrast to increased beta cell proliferation following pancreatectomy or pancreatic injury in younger rodents [7, 15, 41]. However, this plasticity is altered in older mice (>12 months) where beta cell proliferative responses to pancreatectomy, glucagon-like peptide-1 analogue administration and high-fat diet were reduced compared with younger animals [39, 42]. In human islets, there is an age-related decreased expression of the beta cell master transcription factor pancreatic duodenal homeobox factor (donors aged 17–74 years), indicating both a decreased capacity with age for cellular proliferation (decreased plasticity) and reduced insulin formation and secretion [43].
Increased islet size (but not islet number) is associated with obesity in rodents [10] and a small increase in the beta cell population in humans is proposed [4, 12, 44], implicating increased cell proliferation. However, in the present data, there was no relationship of donor BMI (range 16–36 kg/m2) to LB distribution. Similarly, LB accumulation was similar in men and women; pregnancy in rodents is associated with increased beta cells [45]. Our observations do not exclude the potential of ageing beta cells for division, which could be activated by external stimuli, as demonstrated in young rodents [15, 46, 47]. However, if in vivo the increased demand for insulin in obesity or the stimulus of hyperglycaemia in diabetes had resulted in activation of beta cell neogenesis [46] or beta cell division [7], a population of younger cells with lower LB content in obese and diabetic patients should have been apparent. Equally, if normally there was a small (2% is predicted by the mathematical model) but constant turnover of beta cells that was reduced in diabetes, our hypothesis would predict an increased population of aged viable cells with higher than expected LB content. However, no major difference of LB population in diabetes was apparent. Evidence for an age-related decrease in an adaptive proliferative response in islets of mice >2 months old has been described [39]. Similarly, in human organ donors, an age-related decrease of replicating cells has been interpreted as evidence of decreased adaptability [48]. These data taken together suggest that, whereas the population of islet cells is established and not plastic in man after about age 20 years, this point is reached in mice at approximately 1 year; adaptability of young mice to obesity, pregnancy and pancreatic damage may model the potential plasticity of human islets in individuals <20 years of age and not the relatively stable condition in adults.
Whilst incorporation of damaged or senescent cellular material into lysosomes and lipofuscin is a protective cellular response for the ageing cell, accumulation of metals, reactive oxygen species and degradation products of autophaged mitochondria in the lysosomal system may not be entirely a bystander activity [49]; slow accumulation of lipofuscin in the ageing beta cells, whilst not toxic to the cells, could progressively create an increased sensitivity to oxidative damage and contribute to cytotoxic events.
The regulation of insulin secretion is highly dependent on ATP production and there is an age-related decline in both mitochondrial function [19, 50] and glucose-stimulated insulin secretion [16, 50]. Many of the susceptibility genes associated with type 2 diabetes by genome-wide investigations are identified by cancer research as regulators of cell turnover or regeneration [1], but the function of most of these factors in the beta cell are unknown and could be unrelated to cell proliferation, or they might only play a role early in life when the islet cell population is established [3]. Our data suggest that, as with neurons, adult human beta cells are long lived and there is little evidence for substantial islet cell turnover or plasticity in response to insulin demand. This differs from the situation in the commonly used model for diabetes, young rodents. The cellular longevity has implications for determination of causal factors for onset of type 2 diabetes in susceptible individuals and development of therapies.
We are grateful to the following for funding this study: The Wellcome Trust (A. Clark, J. H. Gunter.), Diabetes UK (A. Clark), the European Union (Integrated Project EuroDia LSHM-CT-2006-518153 in the Framework Programme 6 (FP6) and Collaborative Project CEED3 in the Framework Programme 7 (FP7), to M. Cnop), the Fonds National de la Recherche Scientifique (FNRS) and Fonds de la Recherche Scientifique Médicale (FRSM) (M. Cnop), Diabetes Research and Wellness Foundation (S. J. Hughes) and the National Institute on Aging NO1 AG-3-1012 (BH). G. V. Walls is supported by an MRC Clinical Training Fellowship, and provision of old mice was supported by an MRC Programme Grant to R. Thakker (OCDEM, Oxford, UK) and by a grant to A. Clark from the Wellcome Trust. We thank L. Scott and S. Rodgers (Department of Physiology, Anatomy and Genetics, Oxford, UK) for technical assistance with EM, J.-C. Hannaert (Diabetes Research Centre, Vrije Universiteit Brussel, Belgium) for help with morphometry, N. Bodkin (Physiology, Obesity, and Diabetes Research Center, University of Maryland, Baltimore, MD, USA) for assistance with non-human primate samples, P. Rorsman (OCDEM) for critical comments on the manuscript, and F. Grandsard (Department of Mathematics, Vrije Universiteit Brussel, Brussels, Belgium) for discussions on mathematics and probability theory. Part of this work was included in the PhD thesis of M. Cnop whilst working in the Diabetes Research Center, Vrije Universiteit, Brussel, under the supervision of D. Pipeleers and supported by a Fonds voor Wetenschappelijk Onderzoek Aspirant fellowship. We are grateful to C. Genoud and S. Monteith of Gatan, Pleasanton, CA, USA for their considerable help in preparation and interpretation of the 3D EM.
Duality of interest
The authors declare that there is no duality of interest associated with this manuscript.


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J.W. Kuo, "Practical Aspects of Hyaluronan Based Medical Products"
2005 | ISBN-10: 0849333245 | 240 pages | PDF | 1,4 MB
The ballooning body of research devoted to hyaluronan (HA) reflects its enormous potential for various medical applications. There have been many successes of varying degrees in the development of medical products based on HA, but also some setbacks. While there is obviously ample information available on the chemistry and various properties of this macromolecule, is the first book devoted to systematically applying this knowledge to product development.
Based on the author's extensive experience working with HA, this book explores in detail the chemistry, composition, formulation, testing, safety, effectiveness, quality control, and regulatory approval of HA medical products. It begins with a survey of the historical development and recent products based on hyaluronan. Subsequent chapters detail the rheological properties of the molecule and explore the chemical principles and methods forming the technical basis of product development, illustrated by more than 50 figures of chemical structures, reaction schemes, and rheological properties. Individual chapters then consider standards, tests, and analytical methods; safety of HA-based products for their indicated applications; and clinical performance, mechanism of action, and product characteristics.
surveys FDA review documents as well as peer-reviewed journal articles to identify the elements essential to successful product development, namely, understanding the critical issues in the regulatory path and linking clinical performance of the products to their original design.
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Links are Interchangeable - No Password - Single Extraction


text:
I just read about the blame on this site from that highlighted forum post and on the article posted up. That's... sad. But horror doesn't cause bad things to happen, it just gives bad things creative ideas. If you read the second to last chapter of Stephen King's Danse Macabre, you'd know what I mean. I recommend that book, too; it may help a lot with your creative horror stories.
I know crazy things like that stabbing happen every day... and it's hard to imagine that so many people are sociopathic or just crazy. But I guess this site is all about "exposing the werewolf," if I may be so metaphoric, and bringing out the bad before it can do any major harm. Sort of like, "Check yo'self before you wreck yo'self," except you might wreck everybody else, too. Or maybe horror shows us the monster we need to fight to preserve ourselves. And, sometimes, that monster is, well, you. You can take the same theory when it comes to driving and apply it to life: Expect that everyone is out to kill you; whether it's because they make a mistake, because they mean it, or because the conditions are just right to go wrong, expect to die.
But I just got way out of the ball field. I just wanted to say that I will be posting up my story Serenity in White in the next few days. I've got most of it done and an idea of how I want it to end, I just need to write in a few more things.
Happy Hauntings!


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Look at other dictionaries:
vibrancy — [vī′brən sē] n. a vibrant state or quality * * * See vibrant. * * * … Universalium
vibrancy — [vī′brən sē] n. a vibrant state or quality … English World dictionary
vibrancy — vibrant ► ADJECTIVE 1) full of energy and enthusiasm. 2) (of sound) strong or resonant. 3) (of colour) bright or bold. DERIVATIVES vibrancy noun vibrantly adverb. ORIGIN from Latin vibrare shake to and fro … English terms dictionary
vibrancy — noun Date: circa 1890 the quality or state of being vibrant … New Collegiate Dictionary
vibrancy — noun The quality of being vibrant. Syn: vibrance … Wiktionary
vibrancy — Synonyms and related words: bassness, deepness, fluctuation, frequency, frequency band, frequency spectrum, fullness, harmonic motion, hollowness, libration, lowness, mellowness, nutation, oscillation, pendulation, periodicity, plangency,… … Moby Thesaurus
vibrancy — vi·bran·cy || vaɪbrÉ™nsɪ n. vitality, essentiality, powerfulness, vigorousness … English contemporary dictionary
vibrancy — vi·bran·cy … English syllables
vibrancy — See: vibrant … English dictionary
vibrancy — noun having the character of a loud deep sound; the quality of being resonant (Freq. 1) • Syn: ↑plangency, ↑resonance, ↑reverberance, ↑ringing, ↑sonorousness, ↑sonority • Derivationally related forms … Useful english dictionary


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Trimax IT Infra provides cloud computing services, data centre services, IT infrastructure solutions with on-site support across India
Trimax IT Infrastructure & Services has filed a draft red herring prospectus (DRHP) with the Securities and Exchange Board of India (SEBI) for an initial public offering (IPO) of 1.19 crore equity shares of face value of Rs10 each for cash at a price to be decided through the book-building process. The issue comprises a fresh issue of 95.85 lakh equity shares and an offer for sale of 23.91 lakh equity shares by BanyanTree Growth Capital LLC. The issue shall constitute 25.07% of the post-issue paid-up capital of the company.
Trimax IT Infrastructure & Services provides cloud computing services, data centre services, IT infrastructure solutions and turnkey solutions coupled with on-site support across India.
The price band and the minimum bid lot size will be decided by the company and the selling shareholder in consultation with the book running lead managers (BRLMs) and will be advertised at least two working days prior to the bid opening date. The BRLMs to the issue are Kotak Mahindra Capital, Religare Capital Markets and SBI Capital Markets.
Banks will have to credit the wrongly debited amount to the customer's account due to failed ATM transactions within seven days of the complaint from Friday onwards, as against the current norm of 12 days
As per an RBI (Reserve Bank of India) directive, banks will have to credit the wrongly debited amount to the customer's account due to failed ATM transactions within seven days of the complaint from Friday onwards, as against the current norm of 12 days.
However, the number of free transactions allowed at ATMs of banks other than where a customer holds the account would now also comprise non-financial transactions like balance inquiry.
Currently, customers are allowed a limited number of free transactions, generally five, for cash withdrawal and other financial transactions from other bank ATMs, while there is no cap on number of free non-financial transactions like balance inquiry, PIN change and mini statement.
This will change with effect from 1 July 2011, as RBI has allowed the number of free transactions permitted per month at other bank ATMs to be inclusive of all types of transactions, financial or non-financial.
Besides, these free transactions would be available to only the savings bank account holders. The banks have started informing their respective customers about the proposed changes from 1 July 2011.
In one such notification, HDFC Bank said it would charge Rs20 per financial transaction such as cash withdrawal beyond five free ones.
Besides, it would charge Rs8.50 for every non-financial transaction such as balance inquiry, PIN change and mini statement after the five free transactions a month.
At the same time, HDFC Bank said that it "will credit such wrongly debited amounts within a period of 7 working days from the date of the complaint".
As per RBI guidelines, the banks would have to pay Rs100 per day beyond 7 working days, but only if the complaint is lodged within 30 days of the date of the transaction.
In another measure to check any fraudulent use of bank accounts, the banks have also been told by RBI to provide SMS and email alerts to the customers for every transaction from tomorrow, as against the current practice of alerts for only select transactions beyond a certain amount.
Market experts believe many companies were averse to hitting the market because of the subdued market conditions, as well as the fact that firms that did implement their public stake sale plans are trading below the issue price
As many as 15 companies, including Anil Ambani Group's Reliance Infratel, have refrained from bringing out their IPOs so far this year despite obtaining the go-ahead from market regulator SEBI to collectively raise an estimated Rs25,000 crore.
The companies which have let their regulatory approvals lapse since January this year also include Jindal Power, Lodha Developers, Sterlite Energy, BPTP Ltd, Ambience Ltd and Gujarat State Petroleum Corp Ltd.
The list of 15 companies mostly comprises entities from the real estate and power sectors. Reliance Infratel was the first company that failed to launch its Rs5,000 crore IPO before the regulatory approval lapsed on 11 January 2011, while Jindal Power is the latest addition to the list after the approval for its Rs7,200 crore public issue expired on 27 May 2011.
Market experts believe many companies were averse to hitting the market because of the subdued market conditions, as well as the fact that firms that did implement their public stake sale plans are trading below the issue price.
"As the first half of 2011 has seen missing FII inflows, resulting in lukewarm market sentiment, it is surely taking a toll on the IPO market," SMC Global Securities strategist and head of research Jagannadham Thunuguntla said.
In all, 15 public issues were planned with the objective of raising about Rs25,186 crore. Other companies that axed their IPO plans at the last minute include Glenmark Generics, Neptune Developers, Kumar Urban Developers, AMR Constructions, Asian Business Exhibition & Conferences, Kabirdass Motor Company, PCI Ltd and Ankita Knitwear.
"This list is featured largely with real estate and power industries. That may be because real estate is completely out of favour of the market. And power has also become out of favour of the market because of the fact that several IPOs from the power industry in the past have given dismal returns to the investors," he added.
Besides volatile market conditions, a high interest rate regime and a slew of recent scams involving real estate companies are also said to have contributed to the failure of realty players to successfully tap the market to raise funds.


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A decidedly different collection of brilliantly paired fragrance notes housed in an alluring glass bottle decorated with a vintage image of a botanic watercolour flower.
14 customer reviews
beautiful summer scent but can be worn throughout the year. lovely fresh citrus but not too sweet yet very feminine and you then get the undertones of the rosewood. i was expecting to smell like a lush bb that was recently disconned when i looked at the ingredients but it doesnt but that doesnt matter as it smells divine! one spritz seems to last a whlie too. i think i have just found my signiture scent! thanks for stocking this brand B&U


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- 53 total posts
- 2 reviews
- 49 comments
- 2 questions
Reviews & Stories
consultation for facial mole. Philadelphia, PA
Doctor Sobanko apparently does not provide cosmetic mole removal. I wish the info is up to date on this site. Also consultation is not free when you mention Realself, they never heard of it. It's $100.00. I'm pretty confused cause I'm trying to find the best doctor in Philly area to get my mole removed from my face, so I'm spending a lot of time researching. And it's a bit frustrating when... READ MORE
36. Philadelphia, PA
Had a modified wedge this morning. So far so good. I have 9 free days for rest and I'm definitely going to take it. No long walks, only laying down and walking around the house. Bleeding is already slowing down. I had general anesthesia, which at the beginning I didn't want, cause I've been reading many reviews and I thought it's not necessary. But my doctor is doing under it so that's what... READ MORE
Questions from Miramara
Why are edges so bumpy and uneven after labiaplasty and will it change? (Photo)
My doctor said she did a modified wedge labiaplasti. Procedure was 5 days ago. Will this look better and is this how it should look like? READ MORE
Recommendation for mole removal (Photo)
I'm wondering about the best technique and scaring. Thanks in advance READ MORE
Recent comments from Miramara
I got my mole excised by another doctor, I'm trying to write a review but your site doesn't let me cause I already wrote the review?? There can only be one facial mole removal review and one medical provider per face? READ COMMENT
What if you don't have an insurance? READ COMMENT
Thanks. Results are good! READ COMMENT
Can you explain the procedure a bit? Thanks READ COMMENT
It also seems that a doctor didn't do well, cost aside. READ COMMENT


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Senators Coburn, Burr and Sessions Call for More Equitable Ryan White CARE Act HIV/AIDS Funding
September 15, 2006
(WASHINGTON, D.C.) - U.S. Senators Richard Burr (R-NC), Jeff Sessions (R-AL), and Tom Coburn, MD (R-OK) today called for more equitable distribution of Ryan White CARE Act funds, saying the funding disparities and the elevated rate of new HIV/AIDS infections among Southern rural and minority populations must be addressed. Currently, Southern states, which now account for a majority of HIV/AIDS cases in the nation, are being shortchanged in Ryan White CARE Act funding.
The three senators raised the issue at a news conference sponsored by the National Minority Health Month Foundation and the Southern AIDS Coalition.
Ryan White CARE Act funding provides medical care, anti-retroviral treatments, counseling and testing, and other services for HIV/AIDS patients.
"Ryan White CARE Act funding must be distributed more equally among states. North Carolina's waiting list for the AIDS Drug Assistance Program has been close to 1,000 in recent years. This is unacceptable," Burr said. "The Ryan White CARE Act exists to protect and support those living with HIV and AIDS. In North Carolina, we have approximately 18,900 residents living with HIV and AIDS. It is time for Ryan White funds to be distributed more evenly so all patients, not just those living in New York, San Francisco and Boston, can receive the care they need."
A recent Government Accountability Office (GAO) investigation found that several funding schemes in the current Ryan White CARE Act program discriminate against rural and Southern states. States with large metropolitan areas benefit from "double counting" in which those with AIDS who live in cities are counted twiceonce under title I (large metropolitan area CARE Act funding) and again under title II (state CARE Act funding). Funds are currently being distributed based upon cases of AIDS, the end stage of HIV infection, rather than cases of HIV and AIDS. Those living with HIV in Southern states represent the emerging epidemic and therefore are not counted in CARE Act federal funding formulas. Finally, while shortchanged Southern states have been forced to implement waiting lists and other restrictions for AIDS drugs, GAO found that at least one metropolitan areaSan Franciscoreceives funding for dead people and is provided twice the amount of funding per AIDS cases as every other area.
"It is time for HIV and AIDS patients to receive equitable treatment regardless of where they live," Sessions said. "Geography should not be a death sentence, and the South in particular has gotten the short end of the stick. Right now Alabama's patients receive far less assistance than those in big cities, even though Alabama's HIV rate is above the national HIV rate. Lives are on the line and I am committed to moving this legislation forward so that patients in Alabama and every state receive fair funding."
Senator Coburn, a physician who has treated patients with HIV over the past two decades, stated "Congress should put the lives of all those living with HIV ahead of petty parochial and political interests that have stalled the CARE Act reauthorization for the past year and pass the compromise bill before October 1. It is unacceptable that federal funding is being allocated for dead people in one area, while patients in other areas are literally dying on waiting lists for AIDS drugs. The CARE Act must be updated to ensure access to treatment for all Americans living with HIV, promote early diagnosis, and provide more equitable funding that reflects the face of HIV/AIDS today. The discrimination that renders Americans living with HIV in rural and Southern states as having only a fraction of the worth of those living elsewhere must end."
The South has been particularly hard hit in recent years, with seven of the nation's 10 highest AIDS rates located in the region. Most of the growth is occurring in the African American population, especially among African American women. The Centers for Disease Control and Prevention estimates about 40,000 people in the United States become infected with HIV each year, and more than 1 million Americans currently have HIV/AIDS. Over 500,000 Americans have died as a result of AIDS.
The Ryan White CARE Act Reauthorization (S. 2823) legislation was favorably voted out of the Senate HELP Committee in May with only a single dissenting vote. It is awaiting action by the full Senate.


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Go Italy Reds Case
Your Go Italy Reds Case includes four bottles each of
Della Flora Chianti D.O.C.G.
Located inside of Tuscany, Chianti is the home of regal, sought-after wines like this offering from Della Flora, with flavors of tart cherry, red plum, and fresh strawberries that mingle with hints of tobacco, oregano, clay, and dried roses. The Italian government has honored this wine with Denominazione di Origine Controllata e Garantita (DOCG), one of their highest ratings, ensuring that this is one elegant and delicious Sangiovese.
Abbazia Barbera d' Asti D.O.C.G.
Located in the rolling hills between Milan and Genoa, Asti is known for some of the world's best wines and cuisine. The Barbera made in Asti is second to none. This elegant wine is full and dry, with firm tannins and ripe red berry flavors. While Barbera ages well, its youthful nature is especially exciting during the young stages of its bottle life.
Multiple Award Winner: 92-point Gold Medal, Critics Challenge Wine Competition 2016; 87-point Silver Medal, Monterey Wine Competition 2016; Bronze Medal, International Eastern Wine Competition 2016
Bertoli Sangiovese di Puglia I.G.T.
Classics started off great, and developed into something respected, excellent, refined, and reliable. Think gourmet grilled cheese, your favorite singer's surprising 10th album, or Sangiovese wine--the most famous Italian grape, known for its delicate and elegant fruitiness. Bertoli Sangiovese di Puglia IGT croons from the glass with supple berry flavors, silky mouth feel, and a lively encore.


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Meaning and Origin of: Dudley
Search for Names & Meanings Top 100 Names for Boys Top 100 Names for Girls Last Name History & Meaning Name Popularity Tracker Celebrity Names Search for Names by Trait Browse First Names A-Z Browse Last Names A-Z Browse First Names by Origin Browse Last Names by Origin Baby Name Lists How to Choose a Name
Save Name
Boy name origins & meanings:
- Old English : People's meadow
Family name origins & meanings:
- English and Irish : habitational name from Dudley in the West Midlands, named from the Old English personal name Dudda (see Dodd) + Old English lēah 'woodland clearing'.
- Irish (County Cork) : English name adopted by bearers of Gaelic Ó Dubhdáleithe 'descendant of Dubhdáleithe', a personal name composed of the elements dubh 'black' + dá 'two' + léithe 'sides'.
- Thomas Dudley (1576–1653), born at Northampton, England, sailed on the Arbella to Salem, MA, in 1630 with the chief men of the Massachusetts Bay Company. They first settled at Newtown. Dudley subsequently moved to Ipswich but then permanently settled at Roxbury. He was elected four times as governor of the Massachusetts Bay Colony and as one of the two commissioners for the colony when the New England Confederation was formed in 1643. He was one of the first overseers of Harvard University, and in 1650, as governor, signed the charter for that institution. Dudley's seventh and most noted child, Joseph (1647–1720) was also governor of MA (1702–15).


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On the DVD
On the DVD
Linux Mint 16 "Petra"
This month's DVD brings you two great versions of the Ubuntu derivative Mint on a double-sided Live DVD. Linux Mint 16 Mate and Cinnamon are two notable alternatives to the Ubuntu desktop.
Linux Mint 16 "Petra"
This month's DVD brings you two great versions of the Ubuntu derivative Mint on a double-sided Live DVD. Linux Mint 16 Mate and Cinnamon are two notable alternatives to the Ubuntu desktop.
Mate debuts a new, speedier login screen that lets you switch easily between users; a new tool formats USB sticks in FAT32, ext4, and NTFS, and several performance improvements make the user experience more pleasant. The Software Manager delivers software quicker, easier, and with a more informative user interface. System improvements include better support for EFI and Steam, secure search engines, and better help support.
Cinnamon 2.0 adds configurable sound effects for system events, improved user and password management, better edge tiling and edge snapping, and MIME improvements that make it easier to associate applications with file types.
Defective disc?
Defective discs will be replaced. Please send an email to mailto:firstname.lastname@example.com.
- Linux Mint: http://www.linuxmint.com/
- Cinnamon: http://blog.linuxmint.com/?p=2489
- Mate: http://blog.linuxmint.com/?p=2493
- User Guide: http://www.linuxmint.com/documentation.php
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Kolab Now Integrates Collabora Online
Kolab Now subscribers now have access to Collabora Online.
Endless OS, a Distribution Without Internet
A new version of Endless OS has been released.
GitHub Announces Open Source Friday Program
They encourage people to take time out and work on open source projects on Friday.
System76 Announces Their Own Distro, Pop!_OS
Pop!_OS is based on Ubuntu and uses the Gnome stack.
Linus Torvalds Talks About His Motivation
He never tires of working on the Linux kernel.
Debian 9 Stretches Its Wings
The new release of Debian has a very strong focus on security.
Trojan Turns Raspberry Pi into a Cryptocurrency Mining Device
Two trojans in the wild are targeting Linux machines.
Fedora 26 Beta Comes with New Features
The workstation comes with the latest Gnome desktop environment and support for many application build systems.
Raspberry Pi Foundation Merges with CoderDojo Foundation
The two foundations join forces to expand their efforts to reach young people.
Samba Security Hole Patched but Risk is Bigger
Millions of devices that use Samba Server are vulnerable to attacks.


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It only takes a minute to get started. Fill out our uncomplicated sign up form and login to the website.
This step is voluntary but will drastically boost your chances of having members look at your profile. Write a little about yourself, your pasttimes and upload a nice photo of yourself.
Utilise our website's cutting-edge search to pinpoint members who meet your criteria. Or just flip through listings and pinpoint folks that attract you.
Found someone who you're attracted to? Send them a word or two or just a wink and see what develops from there. With a little luck you'll be on your way to a once in a lifetime experience.
You won't regret it


text:
M.Sc. in NGO ManagementThe Global Open University
Price on request
M.Sc. in NGO Management
M.Sc. in NGO Management
M.Sc. in NGO Management
M.Sc. in NGO Management
Important information
|Distance learning
|2 Years
- Master
- Distance learning
- Dimapur
- Duration:
2 Years
Frequent Asked Questions
· Requirements
Graduates of any discipline
Course programme
The two years Distance Learning Master of Science (M.Sc.) in NGO Management conducted by
The Global Open University, Nagaland has been designed for meeting the demand of the growing needs of experts in the fields of grassroot level development, social engineering, rural and urban development, poverty alleviation, health and family welfare, voluntary action and social welfare.
Subjects : First Year
Nationalism and Indian Society
NGO Development
Fund Raising
NGOs and Social Development
Voluntary Organisations : Past, Present & Future
Subjects : Second Year
Resource Management for NGOs
State, Civil Society and NGOs
United Nations and NGOs
Future of NGO Management
Master's Thesis


text:
(Regular POV)
"I told you we should have just gone to the doctors" Rainbow Dash told Twilight as the seven of them (the six ponies, plus Spike) walked through town. They were heading to said doctors, actually.
"Well, you can't really blame her for coming to that conclusion. She doesn't know us that well and our symptoms do match those of
pregnancy" the purple unicorn said, hesitating before saying the last word.
It seemed her hesitation was needed, as the moment she said that word, everyone became oddly quiet.
It was a truth that none of them could deny, but no-pony wanted to admit it.
Based solely on the symptoms, the mares could easily believe that they could be pregnant. But, that was impossible. None of them had been with any stallions, ever.
So, there had to be something else wrong with them-some illness that just happened to have the same symptoms as pregnancy.
Though, if they did have some rare illness, they would have a lot more problems to deal with.
-Ponyville Medical-
Nurse Redheart ushered the six ponies into the room where the doctor was waiting for them, leaving Spike in a play-area with a couple few young colts and their "sitter", much to the baby dragon's chagrin.
The room wasn't very large, so there wasn't a lot of room to stand. Thankfully, the floor was covered with carpeted mats
for some reason, so the girls decided to rest for a few moments before the doctor came in to diagnose them. It was quiet.
A crunching noise broke the silence.
"Pinkie Pie, are you eating a tongue depressor?" Rarity questioned, staring at the pink earth pony as though believing she had lost her mind completely.
Pinkie spat out the half-eaten wooden tongue depressor that was in her mouth and shook her head before returning to the mat she had previously been lying on.
Moments after she sat down, two doctors, an earth pony with a blue-grey coat, a dark grey mane, glasses, and a syringe for a cute mark, the other a black unicorn with green eyes, a white mane, and a cutie mark of what seemed to be the outline of an unborn foal.
"Now, ladies" began the earth pony, "how far along are you?"
Immediately the six mares began to deny that there were pregnant, stating they had actually come to the clinic because Zecora had told them they were expecting foals, something that they knew was impossible.
The doctor chuckled slightly before speaking again.
"I'm sorry, and I mean no offense, but it really is obvious," he told them apologetically.
Almost immediately, Applejack was on her feet.
"Well, no offense to you, but I ain't believin' what you're saying without any proof" she informed the doctor (named Dr. Needles if his nametag was to be believed), who simply smiled and turned his head to the unicorn.
He didn't speak, but the unicorn doctor nodded as though he had.
The black unicorn nodded, and then walked over to Pinkie Pie, who seemed to barely notice him coming towards her.
Silently, he tilted his head towards her swollen stomach, his now glowing horn just barely touching her skin. Pinkie giggled; apparently the magic was tickling her, somehow.
Suddenly, what appeared to be a three-dimensional hologram of an earth pony fetus appeared a few inches away from Pinkie's stomach. The unborn foal appeared to be attempting to suck on something thin and flat.
"Hey, that's the tongue depressor I ate earlier!" Pinkie exclaimed.
The other five sat in stunned silence while Pinkie continued to babble on, even after the doctor moved away from her and the image vanished. One by one, he went to the five other mares, using the same spell on each of them. And, sure enough, the same image appeared each time, with the only changes being that the images for Fluttershy and Rainbow Dash had small nubs where the wings would be on a fully-developed pegasus.
He finished and returned to his place beside Dr. Needles.
"Thank you for your assistance, Dr. Phantom" Dr. Needles said, dismissing the other doctor.
Dr. Phantom nodded and left the room.
It was silent for several moments before Dr. Needles handed each of the girls a small cloth bag containing what he said were some vitamins they would need to take over the course of their pregnancies.
"I'm honestly amazed none of you realized it. I mean, by twelve weeks, an expectant mare can usually tell she's due to have a foal" he said in a tone that sounded somewhat confused.
No-pony responded. Assumedly they were still in shock from the news they had just received.
Deciding it would be best to let them deal with the life-changing news in the comfort of their own homes, he instructed them to leave, saying he would schedule appointments for them.
(Twilight's POV)
-Twilight's Library-
Spike went to bed hours ago.
I really should be asleep, myself. It's already past midnight and I'm still wide awake.
can't believe it. I don't want to believe it. But, I have to. I saw it with my own eyes. My friends saw it, too, so it couldn't have just been my eyes playing tricks on me.
I've been up for hours trying to figure out how it could be possible.
I know I haven't been mounted by any stallions, so how am I pregnant?
I've looked through so many books. I'm on my seventy-eighth one and I'm still not any closer. I'm tired.
What day is it? I use my magic to bring my calendar over to me.
It's Tuesday.
The day I used to send my friendship reports to Princess Celestia, before she changed the rules.
Princess Celestia
Should I tell her?
No, I can't. Not now.
How would I even tell her?
Besides, it's not like she would believe it. I can't even believe it.
And, even if she did, she wouldn't believe me.
She wouldn't believe that I had gotten pregnant without the help of a stallion.
She would be so disappointed.
I can't handle that.
I'll just go to bed. Try and get some sleep.
(Pinkie Pie's POV)
-Pinkie's Loft, Sugar Cube Corner-
Well, it's not all the sweets that are making me fat. It's just a baby.
That's good.
I don't want to get too fat from sweets, but sweets never make me fat, so that's not a problem. I can even eat more sweets, if I want them!
I'll still get fat. That's okay.
It's the baby making me fat, not the sweets.
Baby wants the sweets.
Baby can't get the sweets himself, or herself, or whatever-they-are-self.
I gotta eat the sweets so Baby can have them.
I love making other ponies happy. If Baby needs sweets to be happy, I'm gonna give Baby sweets.
Besides, I like how they taste, too.
(Fluttershy's POV)
-Fluttershy's Cottage-
I'm having a baby. I'm actually having a baby.
I'm so happy.
I know I should be worried about how I'm going to do this on my own. I know I should be wondering how I got pregnant when I've never been with a stallion. But, I'm not worried and I'm not too concerned with how this happened.
I love babies, both baby animals and baby ponies.
I had always hoped to be a mother someday, ever since I was a filly. But, I'm too shy.
I've never been able to talk to a stallion without beginning to shake because of my nerves less than halfway through the conversation. If a stallion ever mounted me, I would probably pass out. I had figured that this meant I would never be able to have a baby of my own.
Now I'm pregnant.
My foal is healthy. I don't know where he or she came from, but it doesn't matter. As long as the foal is healthy, I'm happy.
I'll do whatever I have to do keep them strong and healthy. I already eat healthy, so that won't be a problem.
I haven't told Angel yet.
He has a bit of a cold, so he's been very tired today. If he feels better, I'll tell him tomorrow.
He's been so worried about me since my symptoms began to show.
He must have thought something was horribly wrong with me. He'll be so happy to hear that there's nothing wrong with me.
I can't wait to share the good news with him.
(Rarity's POV)
-Carousel Boutique-
I have to contact Rose and tell her I cannot attend the party that she and her cousins invited me to.
I don't know how I'll explain my sudden cancellation.
Maybe I'll just say that I don't feel well. It is true, after all.
I don't know what I'll do with the dress I had made, however.
It was designed specifically for this party, and there was no way I would be able to fit into it, even if I was to attend the party.
Maybe I'll send it to Rose or Lily. It would look lovely on either of them. I would consider sending it to Daisy, but it would clash too much with her hair.
But, that's nothing I have to decide this instant. I have much more pressing matters to attend to.
I use my magic to bring a small box of sugar cubes to my side, along with a small bowl of rose petal soup. I drop at least a dozen sugar cubes into the soup before beginning to eat. It tastes horrible. I hate the way it tastes. But, I can't stop eating it. Is this what it's like to have a craving? Am I going to spend the time left before I give birth with the desire to eat things that I would normally avoid putting anywhere near my mouth?
Well, I suppose it could be worse. I could want to eat wood and paper like Pinkie Pie.
I also don't have to worry about my business failing as my stomach grows.
Yes, trying to design the perfect dress for some-pony can be stressful, but creating a dress is far from strenuous. So, I'll still be able to make money, which is important.
Now, I know money isn't everything, but I do need to make sure I can purchase food and keep a roof over my head. Especially now.
I lift my head and look around the room. Nothing is where it was this morning. Why did I move all the furniture around? Everything had been perfectly organized before.
I'll have to wake up bright and early in order to reorganize everything again.
Maybe I'll just do the reorganization now.
I doubt I'll be getting any sleep tonight, no matter what I do.
(Applejack's POV)
-Sweet Apple Acres-
Well, guess I can't really deny it. Hard to deny that something exist when you actually see it.
Guess I always sorta knew.
Suppose it's part of holding the element of honesty. I can't lie, even to myself.
This isn't so bad, really.
Least I have my family to help out.
Well, Granny Smith is getting a might too old to be chasing a foal around, but Big Mac and Apple Bloom will help me. I know it.
First I gotta tell 'em, though. I'm gonna tell 'em, soon.
Just not tonight.
Still gotta get used to the idea myself.
Maybe tomorrow, if I'm ready.
If they ask what's wrong with me, I'll tell them.
Even if I'm not totally ready, I'll tell them. I can't lie, not to my family, about something like this.
(Rainbow Dash's POV)
-Rainbow Dash's Cloud-
What am I supposed to do with a foal? I don't even like kids, really.
I don't have any problems with them, but it's not like I'd want to spend a day babysitting. Now I'm going to be stuck babysitting for years.
The thing's not even going to be able to fly until it's already been to school.
I'm going to have to carry it whenever I go to Ponyville and back.
Not like I'm scared.
I've taken care of Scootaloo for a week before. I'm still not entirely sure how she convinced me to let her spend the week at my house
Doesn't matter, though.
That filly is one of the most wild fillies I've seen since, well, I was a filly.
She's calmed down since she and the other Cutie Mark Crusaders finally earned their cutie marks, but she's still pretty wild. I would know.
Ever since she started really flying (she's still not great at it, but I'm not gonna tell her that), she's been spending even more time with me. No idea why she doesn't want to go home.
Anyway, what was I saying? Oh, right.
If I can handle Scootaloo, a foal isn't going to be any problem at all. I can handle this.
Wish I didn't have to, but I can.
Friendship is Magic: Discord Did It Chapter 2 by DarkMasterofCupcakesWatch
©2011-2017 DarkMasterofCupcakes
Disclaimer: I'm not Lauren Faust or Hasbro. Honestly, I'm glad I'm not the latter, since I don't really want to be a company. But, because I'm not either Lauren Faust or Hasbro, I don't own My Little Pony or Friendship is Magic, including any characters from the series. I own this plot, the foals of the Mane Six, and my two doctor OCs in this chapter: Dr. Needles and Dr. Tom Phantom. Anyone who can tell where Tom Phantom's name comes from gets internet cookies.
Sorry this chapter seemed a little jumpy. I wanted to show how each of the girls was handling the news. In order of who is taking it the best to who is taking it the best, I'd say it's Fluttershy, Pinkie, Applejack, Twilight, Rarity, and Rainbow Dash. You could possibly switch Twilight and Rarity, but other than that, it's the right order, I think.
By the way, Dr. Needles saying that the girls are twelve weeks along isn't me forgetting how long ago the prologue took place. The girls have only been pregnant for six weeks, but the foals are as developed as a baby foal at twelve weeks gestation.
Also, before you ask how Pinkie's foal got the piece of the tongue depressor they're Pinkie's foal.
Finally, yes, Apple Bloom, Sweetie Belle, and Scootaloo do have cutie marks in this story.
Sorry this chapter seemed a little jumpy. I wanted to show how each of the girls was handling the news. In order of who is taking it the best to who is taking it the best, I'd say it's Fluttershy, Pinkie, Applejack, Twilight, Rarity, and Rainbow Dash. You could possibly switch Twilight and Rarity, but other than that, it's the right order, I think.
By the way, Dr. Needles saying that the girls are twelve weeks along isn't me forgetting how long ago the prologue took place. The girls have only been pregnant for six weeks, but the foals are as developed as a baby foal at twelve weeks gestation.
Also, before you ask how Pinkie's foal got the piece of the tongue depressor they're Pinkie's foal.
Finally, yes, Apple Bloom, Sweetie Belle, and Scootaloo do have cutie marks in this story.
rarity: Well gotta tell my friends bout how I cant come to the party, not gonna find out how i got pregnant in the first place.
Me: Mmmm. That logic.
Me: Mmmm. That logic.
Dr.Phantom's name comes from the images he projects of the foals.
At Pinkie Pie's POV I started laughing.
Dr. Needles, What a lovely name for a Doctor. XD For some reason, Needles from Back to the Future popped into my head, and I honestly don't know why.
Three doctors in this story: Dr. Needles, Dr. Phantom, and Dr. Castaway. Yeah, I wouldn't trust a guy named Dr. Needles myself, since his talent is apparently sticking people with needles. He is a good doctor, though.
It's kind of strange Pinkie Pie and Fluttershy weren't worried. And I can't blame Twilight for what went though her mind. But why didn't she mention her owl? I remember his name, but can't spell it.
Fluttershy isn't worried for the reason she said: she's wanted a baby for some time and now she's actually getting one. Pinkie is just being Pinkie Pie.
As for Owlysius, I figured he comes and goes, since we don't usually see him at the library.
As for Owlysius, I figured he comes and goes, since we don't usually see him at the library.
Another good one. ^^
More surprises to come then
More surprises to come then
Next chapter is going to be at least some of the girl's families learning about their pregnancies. I know for sure that I'm doing Pinkie Pie with her family on the rock farm and Twilight's parents.
Cool ^^, this'll be good
(sorry for the late reply, it didn't show up on my alerts)
(sorry for the late reply, it didn't show up on my alerts)
Let me put it this way: Pinkie basically uses the worst way to tell your parents that you're pregnant. Basically, tell them you did something bad, like you failed a test, then say, "Also, I'm pregnant."
Sounds like Pinkie Pie.
Bet Clyde's gonna go balistic.
Bet Clyde's gonna go balistic.
He's going to want to meet the stallion who got Pinkie pregnant.


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WASHINGTON – U.S. intelligence officials told Congress on Thursday that disclosure of once-classified projects like President Bush's no-warrant eavesdropping program have undermined their work.
"The damage has been very severe to our capabilities to carry out our mission," CIA Director Porter Goss told the Senate Intelligence Committee, citing disclosures about a variety of CIA programs that he suggested may have been compromised.
Goss said a federal grand jury should be empaneled to determine "who is leaking this information."
But Democratic members of the panel accused the Bush administration of wanting to have it both ways.
"The president has not only confirmed the existence of the program, he has spoken at length about it repeatedly," while keeping Congress in the dark, said Sen. Jay Rockefeller of West Virginia, the panel's senior Democrat.
Rockefeller suggested that such "leaks" most likely "came from the executive branch" of the government.
That brought a terse response from FBI Director Robert Mueller, who said, "It's not fair to point a finger as to the responsibility of the leak."
The sometimes pointed exchanges came as leaders of the nation's intelligence agencies appeared before the panel in a rare public session to give a rundown on threats facing the world.
Committee Democrats sought to change the focus to the president's decision to authorize the National Security Agency to eavesdrop — without first obtaining warrants — on communications to and from those in the United States and terror suspects abroad.
National Intelligence Director John Negroponte, who oversees all intelligence activities, strongly defended the program, calling it crucial for protecting the nation against its most menacing threat.
"This was not about domestic surveillance," he said.
As an indication of how closely the administration held the NSA program, Paul McNulty, the acting deputy attorney general since October, said Thursday he learned of it only when he read about it in The New York Times.
Testifying at his Senate confirmation hearing, McNulty said he does not know whether information gathered through the warrantless surveillance has been used in prosecutions in the Alexandria, Va.-based federal judicial district where he has been the chief federal prosecutor since Sept. 2001.
Two defendants in terrorism cases in Virginia have asked a federal judge to determine whether any evidence against them resulted from NSA eavesdropping.
Goss complained that leaks to the news media about classified CIA programs — such as reported CIA secret prisons abroad — had damaged his own agency's work.
"I use the words 'very severe' intentionally. And I think the evidence will show that," he said.
Goss cited a "disruption to our plans, things that we have under way." Some CIA sources and "assets" had been rendered "no longer viable or usable, or less effective by a large degree," he said.
The revelations have also made intelligence agencies in other countries mistrustful of their U.S. counterparts, Goss said.
"I'm stunned to the quick when I get questions from my professional counterparts saying, 'Mr. Goss, can't you Americans keep a secret?"
Goss, when pressed, said he was speaking of programs run by the CIA, and would let NSA officials speak for themselves.
Gen. Michael Hayden, the principal deputy director of national intelligence and a former NSA director, said it was hard to characterize any damage done to his agency in an open session.
But, he said, "Some people claim that somehow or another our capabilities are immune to this kind of information going out into the public domain."
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Negroponte said great strides had been made in fighting global terrorism.
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But, Negroponte added, the terror organization's core elements still plot and make preparations for terrorist strikes.
He suggested that "high impact attacks" would continue, and said Al Qaeda continues to pursue chemical, biological and atomic weapons in hopes of attacking the United States.
After a public session lasting just under four hours, the committee and its witnesses went into a closed-door session.


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My Witnesses (1 of 14) by Joe Alain
This content is part of a series.My Witnesses (1 of 14)
Series: Acts
Joe Alain
Acts 1:8
Waiting on God
Luke tells of a meeting with the disciples that he also records in Luke 24:48. The message was "Do not leave Jerusalem, but wait for the gift my Father promised" (v.4). The disciples are in an in-between place. They are in a holding pattern. They have seen the resurrected Jesus, but they don't know what all of that exactly means for them. Now Jesus is giving them a mission, a purpose but instead of sending them right out, he tells them to "wait."
It's hard to wait and yet life is full of waiting. At times you may feel as if you're in a waiting pattern flying around in circles wondering when you're going to land. It's frustrating not to know, to have to wait. Maybe you feel that way today. You're life seems to be in a holding pattern. You're waiting for a healing, a spiritual breakthrough, the light to break through your darkness. And yet you are consigned for a time to wait.
That's where the disciples are. They are to "wait" on the Lord and there waiting will be rewarded for in just a few days they will receive the gift of the Holy Spirit, the very presence of God with them, the power to live. But for now they wait and they pray (2:14). There are many times in our journey where we will have to wait patiently on God, and as we do we too will discover that our spiritual breakthrough is right around the corner.
"Wait on the Lord; be of good courage, and he shall strengthen your heart; wait, I say, on the Lord!" (Ps. 27:14)
"Be still before the Lord and wait patiently for him; do not fret when men succeed in their ways, when they carry out their wicked schemes" (Ps. 37:7).
"I waited patiently for the Lord; he turned to me and heard my cry" (Ps. 40:1).
"But those who hope [wait] in the Lord will renew their strength. They will soar on wings like eagles; they will run and not grow weary, they will walk and not be faint" (Isa. 40:31).
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text: Since 'New' is a word which means a time relative to now, it's not an appropriate title to use indefinitely. Should new members be automatically promoted to Member after a certain amount of time? Problem with this is that there is no incentive to participate in the forums to progress from new member to member. Does anyone have any alternative methods of titling members?


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