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Although the HPV-16/18 vaccine is licenced in accordance with a t
Although the HPV-16/18 vaccine is licenced in accordance with a three-dose schedule (Months 0, 1 and 6), a two-dose schedule is under evaluation in clinical trials (Month 0 and 6 or 12). In one recent clinical trial, the feasibility of adopting a two-dose (Month 0 and 6) schedule for 9–14 year olds has been supported on the basis of vaccine-specific antibody selleck inhibitor responses, as assessed by ELISA and on the basis of safety during 24 months of follow-up [6]. Furthermore, two doses of the vaccine appeared as protective as three doses over the four years of follow-up, in one clinical trial where some vaccine recipients did not complete the three-dose schedule [23]. The aim of this study was to
compare the quality of antibody responses in clinical trial recipients of two-doses (Months 0 and 6 in 9–14 year olds) or three-doses (Months 0, 1 and 6 in 15–25 year olds) of the HPV-16/18 vaccine by measuring antigen-specific antibody avidities. An initial step in this study was to characterise a modified ELISA for measuring avidity using the chaotropic agent NaSCN together with samples taken from other clinical trials of the HPV-16/18 vaccine using a three-dose (Months 0, 1 and 6) schedule. In Studies 1 and 2, serum samples were collected at 1-month post-Dose 2 (Month 2) and post-Dose ERK inhibitor 3 (Month 7)
from healthy female human subjects who had received three intramuscular injections (Months 0, 1 and 6) of the HPV-16/18 vaccine from clinical trials NCT00196924 (N = 30, 10–14 years old) and NCT00196937 (N = 35, 15–28 years old; N = 21, 29–41 years old; and N = 34, 42–55 years old) [24] and [25]. In Study 3, serum samples were collected at 1, 18, or 42-months post-last dose (Months 7, 24 and 48) from human why healthy female subjects from clinical trial NCT00541970 who either had received the HPV-16/18 vaccine as two intramuscular injections (Months 0 and 6, N = 30, 9–14 year olds), or three intramuscular injections (Months 0, 1 and 6, N = 30, 15–25 year olds) [6]. The serum samples for the study were randomly selected
from what was available in the clinical trial archives and with respect to the trial participants' identification numbers. All serum samples were stored at −20 °C. All trials were approved by research ethics committees of the respective participating countries and conducted in accordance with the Declaration of Helsinki and Good Clinical Practice guidelines. Written informed consent was obtained from each trial participant who was at least the age of consent. Written informed assent was obtained from each trial participant below the age of consent in addition to written informed consent from her parent/guardian. One Cervarix® dose contains 20 μg of HPV16 Ll VLP, 20 μg of HPV18 Ll VLP, 50 μg 3-O-desacyl-4′-monophosphoryl lipid A (MPL) and 500 μg aluminium hydroxide.
Serum samples, collected on days 0, 21, 42, 64 and 70 were stored
Serum samples, collected on days 0, 21, 42, 64 and 70 were stored at −80 °C until analysis. Sera were tested in HI and VN assays as previously described [31] and [32] against H1N1 A/The Netherlands/602/2009 virus and the two distant swine viruses H1N1 A/Swine/Ned/25/80 and H1N1 A/Swine/Italy/14432/76. In addition
HI serum antibody titers against the distant virus H1N1 A/New Jersey/08/76 were determined (VN assay for this strain was not possible due to insufficient amount of serum). The antigenic distance from H1N1 A/Netherlands/602/2009 to A/swine Netherlands/25/1980, A/swine/Italy/14432/76 and A/New Jersey/08/1976 is Small molecule library high throughput 2.3, 4.4 and 7.7 antigenic units, respectively (unpublished data), on basis of antigenic cartography LY2109761 which allows to quantify HI assay data made with ferret post-infection sera, where 1 antigenic unit corresponds with a 2-fold difference in HI assay titer [33]. On days 0, 1, 2, 3 and 4 after challenge, nose and throat swabs were taken from the animals under anesthesia. Four days after challenge, the ferrets were euthanized by exsanguination under anesthesia after which full-body gross-pathology was performed and tissues were collected. Samples of the right nose turbinate and of all lobes of the right lung and the accessory lobe were collected and stored at −80 °C until further processing. Turbinate and lung samples
were weighed and subsequently homogenized with a FastPrep-24 (MP Biomedicals, Eindhoven, The Netherlands) in Hank's balanced salt solution containing 0.5% lactalbumin, 10% glycerol, 200 U/ml penicillin, 200 μg/ml streptomycin, 100 U/ml polymyxin B sulfate, 250 μg/ml gentamycin, and 50 U/ml nystatin (ICN Pharmaceuticals, Zoetermeer, The Netherlands) and centrifuged briefly before dilution. After collection, nose and throat swabs were stored at −80 °C in the same medium as used for the processing of the tissue samples. Quadruplicate 10-fold serial dilutions of lung and swab supernatants were used to determine the virus titers in confluent MycoClean Mycoplasma Removal Kit layers of MDCK cells as described previously [34]. The animals were necropsied according to a standard
protocol, as previously described [35]. In short, the trachea was clamped off so that the lungs would not deflate upon opening the pleural cavity allowing for an accurate visual quantification of the areas of affected lung parenchyma. Samples for histological examination of the left lung were taken and stored in 10% neutral-buffered formalin (after slow infusion with formalin), embedded in paraffin, sectioned at 4 μm, and stained with hematoxylin and eosin (HE) for examination by light microscopy. Samples were taken in a standardized way, not guided by changes observed in the gross pathology. Semi-quantitative assessment of influenza virus-associated inflammation in the lung was performed as described previously (Table 1) [30]. All slides were examined without knowledge of the identity or treatment of the animals.
As a result, the introduction of this vaccine targeting an infect
As a result, the introduction of this vaccine targeting an infection (HPV) transmitted through sex has been highly problematic in a number of settings – as we explore below. Nonetheless, there is an increasing demand for information about the vaccine
and accessible and affordable http://www.selleckchem.com/products/Gefitinib.html services to deliver it. In the following sections we review the introduction of HPV vaccines in a variety of settings in order to examine what lessons can be learnt for future vaccines targeting STIs. We focus predominantly on the battle of ideas around HPV vaccines, but refer to entrenched interests and stakeholder institutions where these have influenced policy. Human rights laws and principles apply directly in the provision of HPV vaccines. The right to the highest attainable standard of health requires governments to progressively take steps necessary to make services accessible and available, without discrimination, to the maximum of their available resources, and to reduce health inequities [24]. Given the problems with alternative
STI prevention measures, such as screening programmes [25], the benefits of vaccine programmes (in conjunction with other public health approaches) become more clear: vaccines may place considerably fewer demands on health systems than other interventions, Screening Library cost by utilizing established infrastructure, logistics networks and information systems of immunization service delivery [22]. Moreover, studies indicate that HPV vaccines, if made available and accessible to adolescent girls in developing countries, would help prevent a large proportion of cases of cervical cancer in the next decade [26] – and may reduce the burden of other cancers and genital warts too. Thus, the benefits of HPV vaccines are clear from
a human rights perspective, and similar arguments about efficacy and cost effectiveness would need to be made for future STI vaccines. However, vaccines specifically targeted at young adolescents (as these vaccines are and are likely to be in of the future), raise particular issues under human rights law. Introduction of the HPV vaccine or any STI vaccine to young people faces a variety of challenges. The first challenge is ensuring that vaccine delivery is not a stand-alone effort, but supported by engaging young people with comprehensive and appropriate information, including on sexuality [27] and [28]. Cultural and religious norms and taboos in many settings, however, prohibit the exchange of information about sexuality, particularly for unmarried adolescents and young people – often with the effect of limiting care-seeking in this age group [29].
The extract has been used as a pink and purple food coloring agen
The extract has been used as a pink and purple food coloring agent as well as a spice to give a sore-sweet taste. Its syrup is consumed as a soft drink during summer. In addition to food usage, it has also been used as a cosmetic ingredient, as well as a traditional medicine for treatment of inflammation and other disorders. In spite of its wide economical importance, a rapid and efficient method for its identification and quantification is lacking. In addition garcinol is always present along with another compound isogarcinol in kokum fruit. 1, 2, 3, 4, 5, 6, 7 and 8 Hence
a new HPLC 9, 10 and 11 analysis method for simultaneous analysis of garcinol and isogarcinol was developed. The aim of the Selleckchem Nintedanib present study was to develop a rapid, economical, precise and accurate reversed-phase HPLC method with wide linear range and a good sensitivity for Lapatinib the determination of garcinol and isogarcinol. In this study, HPLC instrumentation with UV detection, which is readily available in most analytical and pharmaceutical laboratories, was used. The analytical method was
validated as per current International Conference on Harmonization (ICH) guidelines.12 Acetonitrile (HPLC grade, MERCK), Water (HPLC grade, Thomas Baker) and orthophosphoric acid (AR grade), di-n-butyl phthlate (AR grade), G. indica fruit rind, garcinol and isogarcinol are procured from local analytical laboratories. HPLC is a chromatographic technique STK38 used to separate a mixture of compounds in analytical chemistry and biochemistry with the purpose of identifying, quantifying & purifying the individual components of the mixture. The HPLC system consisted of Agilent 1200 and equipped with quaternary pump G1331A connected with G1314B variable wavelength detector, G1316A thermostatted column compartment, G1329A ALS autosampler. The data acquisition was performed by
Agilent Chemstation software. The chromatographic separation was achieved on Zorbax SB C-8 (150 mm × 4.6 mm i.d., 3.5 μm) column. The elution was isocratic with mobile phase of 0.1% orthophosphoric acid in water and acetonitrile (20:80, v/v). The flow rate was 1.0 mL/min and yielded a backpressure of about 57 bar. The column temperature was maintained at 40 °C, the detection was monitored at a wavelength of 215 nm and injection volume was 5 μL. HPLC is suitable for simultaneous separation of garcinol and isogarcinol with di-n-butyl phthlate as internal standard. The standard stock and sample solutions were prepared with di-n-butyl phthlate in acetonitrile to give the final concentration of 250 μg/mL concentration of both garcinol and isogarcinol. The working standard solution of garcinol and isogarcinol were prepared by taking suitable dilutions. For the analysis of garcinol and isogarcinol in G. indica 200 g of fruit rind was powdered and extracted in methanol.
The larger size particles (0 5–5 μm) are uptaken by macropinocyto
The larger size particles (0.5–5 μm) are uptaken by macropinocytosis, while particles greater than 0.5 μm are predominantly taken up by phagocytosis, and primarily ingested by macrophages [28]. The crystal size of sHZ can be adjusted by the modification of synthetic method, and smaller size sHZ (diameter range; 50 nm–1 μm, peak of the frequency distribution; 50–200 nm) exhibits higher adjuvanticity than larger size sHZ (>5 μm) in mice when immunized with ovalbumin antigen [4]. This size-dependent adjuvanticity of sHZ is considered as the result from the manner of uptake of APCs. In this study, we demonstrated
the potent adjuvanticity of sHZ, which contains approximately 1–2 μm particles. In the present study, we demonstrated that sHZ could enhance the protective efficacy of SV against influenza virus check details in ferrets without causing a pyrogenic reaction. The findings of
this study indicate that sHZ is safe and has great potential for use as an adjuvant for human SV. This study was financially supported by Shionogi & Co., Ltd. a contrated collaboration between NIBIO and Shionogi & Co., Ltd. M.O., M. Kitano, K.T., T.H., M. Kobayashi, A.S., and K.J.I. designed research; M.O., M. Kitano, K.T., T.H., and M. Kobayashi performed research; M.O., M. Kitano, and K.T. analyzed data; M.O. drafted the article; T.H., C.C. and K.J.I. revised the article critically for important intellectual Stem Cell Compound Library purchase content. CC and KJI hold a patent related to synthetic hemozoin. The other authors declare no conflict of interest. We thank Tetsuo Kase from the Osaka Prefectural Institute of Public Health for providing B/Osaka/32/2009 and Makoto Kodama from Shionogi & Co., Ltd. for help
with the animal care and experiments. "
"Streptococcus pneumoniae, a leading cause of bacterial pneumonia and invasive disease, is responsible for approximately 11% of mortality in children under 5 years old worldwide [1] and [2]. Currently available pneumococcal conjugate vaccines (PCVs) contain capsular polysaccharides of the most prevalent pneumococcal serotypes, conjugated to a carrier protein (PS-conjugates). Widespread use of these PCVs has significantly decreased over the incidence of pneumococcal disease [3], [4] and [5]. However, shifts in serotype epidemiology have been noted [4], [5] and [6]. Additionally, an increase in serotype 19A invasive pneumococcal disease (IPD) has been observed in some countries, partly due to multiple antibiotic resistance of this serotype [7], [8] and [9] and no effective control after the introduction of a 7-valent PCV. A substantial disease burden thus remained, necessitating the development of new vaccines that could provide broader protection.
N-glycation is a protein modification that occurs more often in,
N-glycation is a protein modification that occurs more often in, for example, antibodies [20]. Alternatively it could represent heterogeneity of VP1 due to N-terminal proteolysis. A 48-kDa VP1-VP2 dimer was observed in strain O1 Manisa but not in strains of other serotypes. This must represent a disulfide-bonded dimer since only O serotype strains contain a disulfide bond between cysteine 134 of VP1 and cysteine 130 of VP2 [14]. This is confirmed by analysis of tryptic digestion fragments. Trypsin treatment of FMDV strain
O1 Kaufbeuren results in cleavage of the VP1 C-terminus after residue 200 and cleavage in an exposed loop of Volasertib molecular weight VP1, known as the GH-loop, after residues 145 and 154 [17]. We observed cleavages at the same positions in SELDI-TOF-MS experiments of trypsin-treated FMDV O1 Manisa. We also observed a tryptic digestion fragment of 40.0 kDa corresponding to a VP1 degradation product linked to VP2. This confirms the presence of a VP1–VP2 dimer. The spectral peak corresponding to VP2 was predominantly identified based on its mass and because of its specific presence after immunocapture with FMDV specific VHHs. In trypsin digestion experiments we observed two peaks that suggested partial cleavage after VP2 residue 167 both in its single and its VP1 disulfide-bonded form. VP2 cleavage at this position is to our knowledge not observed before. The spectral learn more peak corresponding
to VP3 is more difficult to identify since it is predicted to have a mass intermediate between VP1 and VP2. Occasionally a peak of low height that could represent VP3 is detectable in SELDI-TOF-MS profiles (e.g. Fig. 2c). Furthermore, when the VP1 peaks until are absent due to trypsin treatment a peak at 24.0 kDa that could represent VP3 is visible. However, this peak has a lower height than the VP1 and VP2 peaks. This is unexpected since VP1–VP3 are present in equimolar amounts in FMDV particles [1]. VP3 of all FMDV serotypes is known to form disulfide bonds to other VP3 molecules [1]. Peaks that could
represent multimerized VP3 are readily visible in the spectra of all three FMDV strains, which could explain the low height of the putative VP3 monomer peak. Alternatively, the low height of the putative VP3 peak could be due to less efficient ionization of VP3. We used SELDI-TOF-MS analysis for the characterization of FMDV antigen during various stages of vaccine preparation. In FMDV antigen preparations we could readily detect PEG6000 and BSA as well as many other proteins that presumably originate from the BHK-21 cells used for viral propagation. Especially the ability to detect PEG6000 could be of use since this non-protein compound is more difficult to detect by other methods. We also observed some limited proteolytic degradation of VP1 when FMDV antigen was stored at the elevated temperature of 35 °C, but not when antigens were properly stored at 4 °C.
Consistent with our results, both of these studies confirmed the
Consistent with our results, both of these studies confirmed the high case fatality of IPD due to serotype 3 and 19F. However, many other studies which analyzed death due to individual serotypes were done before the introduction selleck chemicals of PCV7 making a comparison with our study challenging [18] and [30]. As for our setting, considering that the serotypes 3, 19A
and 19F are associated with the highest case fatality, the PCV13 vaccination might be indeed of advantage for adults at increased risk for IPD in Switzerland as those serotypes are included in PCV13. However it can also be expected that the introduction of PCV13 within infants will affect the epidemiology of pneumococcal serotypes within adults which has already been noted within other countries but not yet Switzerland. Our study has several limitations. By including only serotypes with an overall proportion of ≥1% (with the exception of serotype 6C), some serotypes see more were neglected which have also significantly risen but have just not yet reached large enough numbers. In addition, data about case fatality may be incomplete as the physicians have to report IPD to the FOPH within one week after IPD confirmation but some IPD patients may die after reporting. No patient follow up took place. In general, no validation of the
quality of data was performed for this study. Therefore, variation in the definition criteria to report e.g., a chronic lung disease, diabetes or nicotine abuse could have biased our results. A random misclassification would have produced an underestimation of a true association while selective misclassification could have induced a bias in both directions. Finally, the multivariable logistic regression analyses we performed allow to adjust for possible confounding by age, sex and comorbidities of the association
of serotype/serogroup with the analyzed outcomes, but are not capturing the more complex biological interactions between host and bacterial factors in shaping the likelihood of the analyzed outcomes. However, our results are comparable with similar studies from different settings [2], [4], [6] and [20] In conclusion, this is a very detailed population based IPD surveillance study Phosphoprotein phosphatase in adults. It documents that IPD case fatality, age (≥65 years), type of manifestation (pneumonia, meningitis and bacteremia without focus), number (≥1) and type of comorbidities (immunosuppression) are significantly and independently associated with serotype. It furthermore identifies the single serotypes driving these observations (e.g., 3, 19A and 19F for case fatality). The results may therefore help as an epidemiological basis for future vaccination recommendations to prevent IPD in distinct adult groups at risk in Switzerland. We thank Dr. Andrea Endimiani for his critical reading of the manuscript and Chantal Studer for her help with the serotyping.
Eight to ten week old female New Zealand White (NZW) rabbits were
Eight to ten week old female New Zealand White (NZW) rabbits were immunized subcutaneously with saline (naïve) or 1/4th (5 μg each HPV16 and HPV18 VLP) the human dose equivalent of Cervarix® at W0, W4 and W12. Eight to ten week old female NZW rabbits were selleck kinase inhibitor immunized subcutaneously with 5 μg each of the indicated in
house L1 VLP (or 5 μg each of HPV16, HPV18, HPV39 and HPV58 for the tetravalent preparation). VLP were absorbed onto 3% alhydrogel (250:1 (v/v), Superfos Biosector) for 1–2 h at room temperature under gentle rotation. For the final preparation of the rabbit inoculum, the VLP-alhydrogel mix was diluted in sodium phosphate buffer pH 6.5 (final concentration 2.7 mM NaH2PO4 and 3.3 mM Na2HPO4) with 150 mM NaCl, alhydrogel (250 μg/mL Al3+), Sigma Adjuvant System (25 μg/mL monophosphoryl lipid), and incubated with gentle rotation at room temperature for a minimum of 15 min. Rabbits received additional immunizations at W4 and W12. In all cases, serum samples were collected prior to the first immunization (pre-immunization) and two weeks Selleck BMS777607 following both the second and third doses. All animal husbandry and
regulated procedures were carried out in strict accordance with UK Home Office guidelines and governed by the Animals (Scientific Procedures) Act 1986 which complies with the EC Directive 2010/63/EU and performed under licences PPL 80/2537 and PPL 70/6562-3 granted only after review of all the procedures in the licence by the local Animal Welfare and Ethical Review Bodies. L1L2 pseudoviruses representing Alpha-7 and Alpha-9 HPV genotypes and BPV, and carrying a luciferase reporter, were expressed from transiently transfected 293TT cells, purified and characterized as previously described [20] and [36]. The equivalent of a Tissue Culture Infectious Dose 50% (TCID50) was estimated using the Spearman-Karber equation and a standardized input of 300 TCID50 was used for all pseudoviruses. Serum samples were
else serially diluted and the 80% reciprocal neutralization titer estimated by interpolation. Heparin (H-4784; Sigma–Aldrich, UK) was included as a positive inhibitor control and as an indicator of inter-assay reproducibility. The median (Inter-quartile range, IQR) inhibitory concentrations (μg/mL) were as follows: HPV16 11.9 (9.5–22.3; n = 7), HPV31 5.1 (3.3–8.1; 6), HPV33 13.1 (7.4–19.4; 6), HPV35 3.1 (2.9–4.9; 6), HPV52 25.2 (13.6–31.9; 6), HPV58 8.2 (3.6–19.4; 6), HPV18 3.9 (3.4–5.0; n = 6) HPV39 5.8 (4.0–7.2; 5), HPV45 3.7 (3.5–3.9; 6), HPV59 13.6 (11.7–16.3; 6), HPV68 7.0 (6.5–12.1; 6) and BPV 73.5 (59.1–75.9; 5). Serial dilutions of selected final bleed rabbit sera were pre-incubated for 1hr at room temperature with 2 μg of L1 VLP (HPV16, HPV31, HPV33 or HPV58), followed by addition of 300 TCID50 of L1L2 pseudoviruses representing the same HPV genotypes for 1 h at room temperature, before being transferred to 293TT cells for 72 h at 37 °C.
For example, Kaltoft et al [48] demonstrated that a serum broth
For example, Kaltoft et al. [48] demonstrated that a serum broth (beef infusion supplemented with horse serum and blood) improved the ability of traditional methods to detect multiple serotypes. Similarly, Carvalho et al. [49] found that an enrichment step in Todd Hewitt broth supplemented with yeast extract and rabbit serum increased NLG919 concentration the proportion of specimens with pneumococcus identified, as well as increasing the detection of multiple serotypes by culture and molecular methods. However, there are some remaining
concerns with broth culture-amplification. The pneumococci may be overgrown by other species, and not all pneumococcal strains or serotypes grow at the same rate in vitro [50], [51] and [52]. Moreover, broth culture enrichment may reduce detection of co-colonization of other species [53], or may not be appropriate for all sample types. In addition, some media components (such as animal serum) may be difficult to access in developing countries. There is insufficient evidence to make a recommendation regarding inclusion of a broth culture-based enrichment
step for the detection of pneumococci. Quantification of pneumococcal load should not be determined using samples that have undergone MLN0128 in vivo broth enrichment. Whole-genome amplification methods may overcome limitations of low amounts of DNA. It would be useful to optimize broth culture-amplification (e.g. by including a selective agent), and to test the effects of broth-culture amplification on culture and molecular-based identification and serotyping methods. These recommendations establish the minimum set of criteria to determine the presence of pneumococci, Sodium butyrate and the dominant pneumococcal serotype, in order to ascertain the prevalence of pneumococcal carriage and the serotypes present in the overall population under study. Given this objective, there are two main issues to consider: how many colonies to
pick, and how to select them. Detecting multiple serotype carriage is important for some epidemiologic questions, but serotyping a few colonies is an insensitive method to detect the true prevalence of multiple serotype carriage [54], [55] and [56]. For colony selection, the truly random approach (e.g. where the STGG medium is diluted and spread on agar plates to obtain single colonies, then all the colonies are numbered and selected using a list of random numbers) may be optimal statistically, but is considered impractical for routine use. Choosing colonies based on morphology is more efficient [54], but leads to a bias towards detecting those that are morphologically distinct such as serotype 3 or nontypeable (NT) pneumococci [57]. Select one colony from the selective plate. If more than one morphology is present, this colony should be from the predominant morphology.
55 The two key regulatory enzymes that
55 The two key regulatory enzymes that selleck kinase inhibitor catalyze glycogenesis and glycogenolysis are glycogen synthase and glycogen phosphorylase. Glycogen synthase is the rate-limiting
enzyme in glycogen metabolism which catalyzes the transfer of glucose from UDP-glucose to glycogen in animal cells. Because of its central role in glucose homeostasis, glycogen synthase is responsive to endocrine factors, including insulin, glucagon, and catecholamine, as well as to metabolic status, such as the concentration of the allosteric activator glucose-6-phosphate (G6P). Further, the decreased glycogen content in diabetic disorder is due to the increased activity of glycogen phosphorylase and decreased activity of glycogen synthase.56 Glycogen phosphorylase, a rate-limiting enzyme of glycogenolysis, cleaves α (1, 4) linkage to remove glucose molecules from the glycogen. During diabetic conditions, the glycogen levels, glycogen synthase activity and www.selleckchem.com/products/SB-431542.html sensitivity to insulin signaling are lessened and glycogen phosphorylase activity is significantly amplified.57 Oral administration of fruit extract to diabetic rats regulated the activity of glycogen metabolizing enzymes thereby alleviated the altered glycogen content. The activities of citric acid cycle enzymes such as isocitrate dehydrogenase,
α-ketoglutarate dehydrogenase, succinate dehydrogenase and malate dehydrogenase in the liver and kidney of control and experimental groups of rats were significantly (p < 0.001) low in the liver and 17-DMAG (Alvespimycin) HCl kidney of STZ induced diabetic rats when compared with those in control rats. The activities of these enzymes were found to be significantly increased to near normalcy in MFE as well as gliclazide treated diabetic rats. The normal β cell, highly dependent on mitochondrial energy is the only cell, which increases its function (energy production) during hyperglycemia.
During diabetic condition, the activity of the enzyme glucokinase is found to be lessened due to defective insulin release. This in turn affects phosphorylation, the first step in glycolysis which is glucokinase dependent. 58 Thus, glucokinase mutations can directly impair glucose sensing, while mitochondrial DNA mutations can indirectly impair glucose sensing by reducing intracellular concentrations of ATP, oxidation of glucose derived acetyl residues increases in a time related and concentrations dependent manner when islet or purified β-cells are exposed to a rise in hexose concentration.59 It was proposed that the increased oxidations of glucose derived acetyl residues is attributed to Ca2+dependent activation of NAD-isocitrate dehydrogenase and α-ketoglutarate dehydrogenase. In pancreatic β cell, redox imbalance is reported to potentiate apoptosis.60 Apoptosis or programmed cell death has also been implicated in diabetic retinopathy and neuropathy due to abnormalities in mitochondrial function.


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I think most of us kind of resist change. Even if we want change, we know that it takes work or entails something irksome like a rumbling stomach. People seem to get upset or just complain at the slightest changes, like the weather. But we should know that it is only temporary. Feelings are temporary, the way our body feels is temporary, and our interests can even be temporary.
It is drastic change that often disrupts us and leaves us shaken. People entering and leaving our personal life, moving homes or to a new city, our body's condition and tolerance. We all have witnessed people who have gone through forced change or chosen change. Sometimes our course is to change a little bit over time, or through one big herculean effort. Underneath everything anyone ever does, even the stupidest of things, there is belief it is going to make things better.
If we ever follow any artist, we usually notice how their work changes over time and in much correlation with what is going on event wise. Lately the word, metamorphosis, has sprung into my mind. I began thinking about this oboe work I once played called Six Metamorphoses Over Ovid by Britten written in 1951, which is based on the books written by the Roman poet Ovid in AD 8. Many works of music, literature, and art have been based on Ovid's piece including Shakespeare's Romeo & Juliet. Metamorphoses means 'transformations' and we often think of it when we think about caterpillars changing into butterflies.
The season is transforming into spring. Even though it snowed today in my city, people are beginning to think about spring fashions, spring cleaning the house, doing a detox diet, and embellishing on outdoor activities. But we can also think about what we do on a daily basis those 360 days. It can be hard to break habits of spending too much time with television, the internet, toxic people, shopping, or sitting and doing nothing. I know I have felt this way as of late. Really, I would like to spend more time creating. I know I must change my habits. We can always initiate change instead of waiting for it to just happen. Sometimes we just get tired and we have to push ourselves to do something different. Somehow, our minds tie change & risk. We will never get anything different if we don't do different. There are a few significant areas in our life that we often witness change.
People come and go in our lives. This is often a signal of change, and that we must learn something from it. Even if we know some of them a very long time, we can always count on meeting new people and loosing some. You make new friends when you're out in new places. You may stay friends forever, or one may take a different direction in life. People change, and therefore relationships with people will usually change too. This doesn't always mean you take separate paths, it just means the relationship changes. Just because there is change, doesn't mean you have to give up a relationship. However, sometimes the change in people is so great that the relationship must fade and the person moves on to something else needed.
People are having to reinvent themselves all over again. People are tired of red tape, crappy bosses, stress, and the doing the same repetitive thing everyday. We are dynamic creatures and we are learning that more worthy it to do what we like instead of slaving. Our jobs, careers, employment, are temporary. What we do becomes who we are. Sometimes our job doesn't keep up with who we are.
At the core, our lifestyle equals all the time we spend. Living life is an art form. Some do it in an eclectic manner, some gracefully, some just disjunctive. We constitute our lifestyle by how we spend our time through our career, through our fellow humans, what we eat, if we keep things tidy or messy, where we prefer to live, what type of transportation we take, what activities we do. How we spend our time tells us what we value. It's time to question what you're valuing. Society makes certain lifestyles appealing because it helps society fit into a defining flow. This flow makes it easy for the rest of society to determine what we want and need. What does it mean to have a lifestyle that doesn't fit into society? How are we living and conforming to what we believe we should be doing just because that is normal? Changes in our lifestyle happens when our body and mind is out of the rhythm of flow. Many of us don't realize how far we are from flow because it has just been too long.
I hear a lot about how our environment shouldn't influence how we feel or think. I think that's crap, especially as a designer. There are all kinds of studies about how our environment influences our work productivity. Maybe a zen master can be in peace anywhere, but the typical person is going to be influenced by what their senses are determining as pleasing or uncomfortable. Why else do we listen to music, go see art, go on vacation, toss leftovers after a few days, and decorate our homes. We can learn from the zen, by not letting every little thing bother us. However, we need contrast in our lives to witness the good. Change is all about having contrast. We are on a constant search for something fresh. How we go about that determines our character.
"Change is all about having contrast." Love it. I think a big part, too, is accepting opposites, or perhaps moving beyond the illusion of opposites. This is a recent thought. I have to think through it. This post got me thinking even more.
I like how you address environments and lifestyle. I think it would be difficult to be a prisoner in a plain gray cell, for instance, and still be free in your mind. It would take a very strong, as you say, "zen master" mind. Mind/body are really not separable so making positive spaces that provide enough contrast (unlike say, cubicle work environments) is important. I think that's one reason I need consistent breaks to get out of my workplace or take a walk on campus. Meditation isn't enough. And the busier the week, the more necessary it is.


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Home → Kansas
Peek-A-Boo, Kansas Gov't Pensions-We See You!
By temp-admin on February 29, 2012 / Kansas, Latest, News Releases, Pension Reform
Click here to view as a PDF
KANSAS – Taxpayers United of America has released the top pension estimates for Kansas government teachers and employees. "We are shedding light at last, on the problems with Kansas' government pension system," said Christina Tobin, Vice President of Taxpayers United of America (TUA), and founder and President of Free and Equal Elections. "Minimal reform has occurred in Kansas as legislators consider measures that do little to actually solve the problem. Much more pressure is needed from taxpayers," she said.
"Kansas' government pension system desperately needs reform. Releasing the specific names and pension amounts would show who's really benefitting," said Tobin. "But Kansas refuses to release actual individual pension payments and that really raises questions when estimates range to nearly $8 million. So, why won't the Governor let Kansans see the facts?"
"There is no fair representation of taxpayers. This is a nationwide problem that burdens the Left and Right alike, and has fueled the financial crisis facing taxpayers and retirees. The urgency of this crisis is illustrated by the extensive press coverage that our government pension reports have received throughout Kansas."
Tobin, who toured through Kansas towns revealing top government pension estimates to the public, received coverage from KSN News Wichita, KWCH 12 Eyewitness News, Salina Journal News, KSALLink.com, Wichita Business Journal, Kansas City Business Journal, and Fox 4 Kansas City.
TUA will be exploring all options to get the information still being withheld by the government bureaucrats of Kansas, released. "I have written letters to Governor Brownback and the members of the Kansas Legislature, asking for transparency. As long as taxpayers feel the pain of the hefty bill for these pensions, those payments should be available for public review." Tobin plans to work with legislators but does not exclude the possibility of filing a lawsuit to obtain the information.
TUA will be revealing more States' pensions across the nation, including those of Pennsylvania, New York, and Arizona in the coming weeks.
KSN News Wichita | Grassroots group brings pension reform message to Kansas
By temp-admin on February 24, 2012 / Kansas, Press
Findings from TUA's pension project on Wichita, Kansas, are featured in this story from KSN News Wichita.
WICHITA, Kansas (KSN) — A grassroots group took their message of pension reform to Wichita hoping to shock citizens into action by releasing some stunning figures showing their estimates of what some city employees will make during their retirements from government pensions.
"We do intend to sensationalize the numbers and we do intend to outrage taxpayers," said Raeann McNeilly with Taxpayers United of America.
McNeilly and the organizations vice president, Christina Tobin, have been traveling the nation by car and stopping in cities like Wichita with their message of pension reform. They say it's the top challenge facing states looking to balance their budgets.
"This is serious," said Tobin. "This means these checks will stop coming if we don't have real reform here in Kansas."
Pension reform was a goal of the legislature this year in Topeka but efforts to reform KPERS have stalled.
They were also critical of Kansas officials for refusing to release the firm figures on pensions. Taxpayers United used salary figures from 2010 to estimate what city employees will make in pensions based on a life expectancy of 85.
"They release the pension numbers but not the names next to the pensions", Tobin complained. "It's the first state we've ever encountered like this."
A spokesperson for City Hall says the numbers provided by Taxpayers United are "generally misleading, taken out of context and in some cases inaccurate".
KWCH 12 Eyewitness News | Taxpayer group releases local officials' salaries and estimated pensions
Findings from TUA's pension project on Wichita, Kansas, are featured in this story from KWCH 12 Eyewitness News.
(WICHITA, Kan.)—Wichita City Manager Robert Layton, Police Chief Norman Williams, and Fire Chief Ron Blackwell are a just a few of the city employees Taxpayers United of America use as examples.
The group, based in Chicago, was in Wichita Thursday to bring awareness to public pension funds.
It wants the current system changed so new public employees pay into a private retirement system and current employees pay more into the system which it says is unsustainable.
"We want all of the current employees to put more in…10 percent more. If they don't the system will collapse and they will get nothing," says Christina Tobin with Taxpayers United of America.
The group lists the top 25 "estimated" pensions of city, county, and state employees. It wants Kansas to release the actual pension amounts of current and retired employees.
"We're here to shed a light on the need for transparency in Kansas." says Tobin.
Tobin says the group can only estimate pensions based on the state formula and 2010 salaries.
"We're here to urge Governor Brownback to release the pensions with the names."
The group would not disclose its donors.
It says it names employees to get attention and admits the numbers are only estimates and are at the high end.
"If I don't see the names with the numbers I can't relate to what they meet. Yes, we do intend to sensationalize the numbers and we intend to outrage taxpayers. It's the outrage with taxpayers that's going to cause them to contact legislators and bring about change," Rae Ann McNeilly, director of outreach with Taxpayers United of America.
It says it wants to introduce legislation in Kansas to change the current formula, but says it's still searching for a lawmaker to sponsor the bill.
Attached are links of public employee salaries and estimates by Taxpayers United. The group says it did not attempt to contact any of the employees on the list.
Below are formulas used by the group to estimate pensions:
For non-police/fire
((2010 Gross x 0.6125) x (24 years)
For police and fire
((2010 Gross x .80) x (30 years)
Taxpayers United Of America: (TUA). is a nonpartisan, 501(c)(4) taxpayer advocacy group. Founded June 27, 1976 in Chicago, Illinois by activist and economist Jim Tobin, TUA works on behalf of taxpayers to reduce local, state, and federal taxes. In the past forty years, TUA has saved taxpayers more than $200 billion n taxes and has become one of the largest taxpayer organizations in America. Check All posts. s.
Chicago, IL 60606 205 W. Randolph Street, Suite 1305
Website: https://taxpayersunitedofamerica.org
Email: info@taxpayersunited.org
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Welcome to the 23rd Annual Bell Harbor Classic Weekend!
Online registrations are now being accepted for the largest event on the PNW Classic Yacht Association calendar. Space is limited so please register soon.
Registration and moorage for participating CYA member classics is complimentary Friday and Saturday nights. Registrants will receive final information in early June, and slip assignments shortly before the event. You must contact Bell Harbor Marina (206-787-3952) to reserve a slip if you plan to arrive before June 14 AND contact CYA Dock Master Bob Irving, (bobI@legacy towers.com) to coordinate and confirm that slip assignment.
A formal "Sail-In" takes place on Friday afternoon 6/14. Classics will gather off Elliott Bay Marina near Pier 91 at 2pm and parade along the Seattle waterfront to Bell Harbor. Parade logistics and instructions will follow at a later date.
Friday evening: The arrival ceremony will commence at 5:30pm with an official welcome followed by a wine tasting sponsored by Structure Cellars. There will be light snacks and dessert from member BJ Last's Bakery, Borro Bay.
Saturday morning 6/15: Pastries, coffee and juice provided from 8am to 9:30. The public will be invited to tour the docks and board open vessels from 10am to 4pm on Saturday. Boarding is optional at owner's discretion. Attendees will be provided a Rendezvous window sign describing their yacht and its history, as well as an open/closed window sign.
Saturday evening - 6pm: Catered steak and salmon dinner on the plaza, $30 per person. Payment for the dinner must be received when you register. Please bring at least $5.00 per person to tip the caterers.
Father's Day Sunday morning 6/16: Omelet breakfast provided from 8am to 9:30. Vessels open to the public 10am-4pm on Sunday.
Visitors to the show will be receiving the customary printed program listing participating vessels. First-time attendees, please provide a brief description of your boat and its history for the printed program, You can do it in the registration form which allows 100 words maximum. All participants' information will be posted on line prior to printing for your approval and/or comments.
Program questions? Contact: Jim Paynton, maranee1940@comcast.net or phone: 206-708-9508.
We expect all participating vessels will allow rafting, if necessary, and will remain in their slips until the show closes at 4 pm on Sunday. Moorage is available for Thursday and/or Sunday night by arrangement with the Harbormaster's office. If you choose to stay extra nights, please coordinate your slip assignment with CYA Dock Master Bob Irving.
To register, follow the link below. To assure your boat is listed in the printed program, please submit the online registration form no later than May 24th.
Please refer to this page for ongoing updates and announcements.


Here is another trait incorporated into the nature of the virtuous woman, who is being described throughout the majority of this chapter. This is the Lord's definition of a virtuous woman, and is good for all women to glean from.
That being said, it isn't a good thing for the guys to be found without the majority of the traits demonstrated through these verses. Also, keep in mind of the spiritual side of these scriptures, which is the Lord's intended nature of the Church at large.
We've talked about her diligence toward her family and properties. We've observed the richness of her ways while tending to the needs of not just her family, but those of her servants as well. Now in the verse above, we get a glimpse of an outward expression of charity.
Above, we see another side to this magnificent woman. One of charity, kindness, and meekness.
There's more going on here than having money and giving some of it to those in need. Yes, the expressions above do represent giving, but certainly is not limited to that category.
There's no showing of recoil as it relates to interaction with the poor, just the opposite.Meekness is a heart condition that the Lord favors. This is one of those traits that when openly expressed, is an active weapon against pride.
The perfect example of meekness, is the Lord God Almighty – Creator of Heaven and earth and all which is in-between, taking the time to remove himself from his throne of glory, and rolling around in the dirt in order to play with his children.
In a sense, he did so in the person of Christ Jesus. I don't know about you, but I can't think of a greater expression of meekness than those performed by Jesus, from birth to resurrection.
Perhaps the strongest act of meekness was allowing his love and obedience to the will of the Lord. These kept him on task while in agony on the cross.
Rather than having enough of the torment, and doing what you or I would do… Get off the cross, kick gluteus maximus and take names. If he did so then, where would you and I be today? He had to stay on that cross – Meekness at work.
The virtuous woman is outwardly expressing an act of meekness by outstretched hands toward the poor and needy. She's not placing herself above anyone, or "giving down" to anybody.
Have you ever seen that? Someone pridefully giving, making the needy person feel ashamed for being needy, and receiving what was given?
Honestly, this is a great example of what Jesus described as being a whitewashed tomb. Giving the appearance of Godliness yet inside are full of dead men's bones.
Self-righteousness kicks in when true righteousness is wanting.
Meekness is a powerful display of righteousness when coming straight from the condition of the heart. That, along side charity and good will, is what's being displayed by the outstretched hands of the woman of virtue.
22 But the fruit of the Spirit is love, joy, peace, longsuffering, gentleness, goodness, faith, 23 Meekness, temperance: against such there is no law. 24 And they that are Christ's have crucified the flesh with the affections and lusts.
4 I therefore, the prisoner of the Lord, beseech you that ye walk worthy of the vocation wherewith ye are called, 2 With all lowliness and meekness, with longsuffering, forbearing one another in love; 3 Endeavoring to keep the unity of the Spirit in the bond of peace.
12 Put on therefore, as the elect of God, holy and beloved, bowels of mercies, kindness, humbleness of mind, meekness, longsuffering; 13 Forbearing one another, and forgiving one another, if any man have a quarrel against any: even as Christ forgave you, so also do ye.
Thank you for your Word, and for leading us through it by your Spirit. Help us to do the things you say to do, and change our hearts to be pleasing in your sight. Change us from the inside out concerning meekness, charity, love of the brethren, obedience to you and your Word, and our overall day to day actions. May the contents of our hearts be purified, and those of you magnified. In the name of the Lord Jesus Christ we pray.
When coming across the poor and the needy, do you do so with outstretched hands?


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Whitsunday Coast Guardian Digital Edition
Girl shocked by tap has brain damage
Denishar Woods remains in a critical condition after being electrocuted by a garden tap. Picture: 7 News
by Ben Graham
7th Mar 2018 11:57 AM
DOCTORS have confirmed that Perth schoolgirl Denishar Woods sustained brain damage after being shocked by a tap.
Her mother now says she doesn't know if or when her 11-year-old daughter will wake up after the freak accident on Saturday - when Denishar was tragically electrocuted by the outdoor tap at her family's public housing property in Beldon.
And now a potential multimillion-dollar claim against the West Australian government looms, a prominent lawyer told AAP.
Denishar is in a critical condition at Princess Margaret Hospital after touching the tap and her mother Lacey Harrison, who was also jolted by the current when she pulled her daughter out of the electrified water, told reporters she couldn't explain how she feels.
"Doctors don't know how bad the damage is and couldn't say if or when Denishar will wake up," Ms Harrison told Perth Now.
"There's no words to explain what I feel. My girl's not my girl any more. I thought she was just going to wake up."
Lawyer John Hammond said the Department of Housing's responsibility to ensure the safety of public housing was clear.
"If the young girl dies, the mother and all the siblings who were present would have a claim against the state for nervous shock," Mr Hammond told AAP.
"If she survives with horrendous injuries, then as a minor, she will have a massive claim against the state as well. It would be a multimillion-dollar claim."
In addition to offering counselling, the state government should also agree to pay for all medical costs, which could be done without admitting liability, he said.
Denishar Woods suffered an electric shock after using a garden tap. Picture: 9 News
Ms Harrison told ABC that her daughter's organs reached 38C and she was on a cooling pad in hospital to try to limit the damage.
"There's no signs of whether or not she's going to pull through. They're just keeping her organs cool," Ms Harrison said.
Housing minister Peter Tinley told reporters on Monday responsibility for the incident would only be established once an investigation was complete.
Mr Hammond also said all public housing should be immediately checked in light of the incident.
Michael Bunko, a director at WA's electricity regulator, believes the tragedy was likely caused by a fault in the neutral conductor supplying power to the property.
An upstream "open circuit neutral" could be caused by corrosion, a loose connection and in some cases, poor workmanship, Mr Bunko said, and residual current devices would not protect against them.
"If you get a fault upstream, generally before the main switchboard where the electricity is coming in, the RCD can't see it and won't operate," he said. Mr Bunko said the girl likely suffered a shock up to 230 volts AC and anything above 50 volts AC was dangerous.
A spokesman for Mr Tinley said safety devices fitted to electrical systems at public housing properties were checked annually at inspections.
Mr Tinley said the family would be immediately accommodated elsewhere if they didn't want to remain at the property, where the power has been cut off to make it safe.
"If we have to put them in a hotel or a motel, then we'll do that," he said. "Clearly, they wouldn't have a lot of faith in the property. They won't be expected to move back into it."
He said he was not aware of the family's claims they had complained more than once about short-circuiting.
Mr Bunko said open circuit neutrals were less common in new houses because they had a lot of plastic pipework.
"If you do get electric shocks off taps or you notice that your lights are dimming for no good reason, then you need to report it to the network operator," he said.
- with AAP and Megan Palin
Teen dies after headphones 'melt in her ears'
Pregnant wife's heartfelt tribute after workplace tragedy
Kevin Rudd, Gillard warned on home insulation risks: ABC
Woman's shock as lightning hits transformer
Electric shock victim's emotional return home
brain damage electrocuted millionaire
premium_icon Memorial unveiled to honour victims of Cyclone Ada
News A memorial was unveiled on the Airlie Foreshore, on Saturday, to honour those who lost their lives in the terrible disaster, in January 1970.
Weather A mini bus has been swept away and cars, caravans and tents are underwater after flash flooding swept through a popular family caravan park on the Gold Coast.
premium_icon 'Notorious' bikie's new life revealed
Crime A former bikie who spent Christmas in jail has told his massive social media following about his big plans to reinvent himself in 2020.
premium_icon Clipper crews slip lines, and get ready to set off to Sanya, in...
premium_icon Hero's welcome home for our returned firefighters
People and Places Bittersweet moment as firefighters return from NSW inferno. 'It just about brings a tear to your eye'
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News A man has been airlifted to hosptial following a two-vehicle crash, in which one...
premium_icon Man killed in Bruce Highway crash identified
Breaking The Bruce Highway has reopened after an earlier crash
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Bwahahaha! This is turning into equal parts Ducati and Honda now. Congrats!
Chip, the track day looks like fun!
I think the float valve in one of my carbs got stuck last night. Every time I turn on the petcock gas just dumps out of the overflow. Guess it's time to finally break it down and clean them.
Thanks for the tip! Even a quick fix would be preferable right now. I plan to tear it all down this winter and wasn't really looking forward to working on it in this heat.
Hopefully the XS400 will be back on the road this weekend. Waiting on parts to arrive and finding time to work on it has delayed me more than expected. At least it's getting some upgrades along the way. New pics coming soon!
I've made some progress getting the XS400 back on the road. I wish I had more time so this would get finished up quicker! The seat got cut down a little and recovered. Not the best job, but it'll do for now. I removed the rear fender and came up with a custom setup for the rear light and plate bracket. It's not in the final location, but close.
That tail light looks OEM, nice job!
That's pretty amazing. It's not cheap, but when you consider the advantages and what it could prevent in terms of safety it would pay for itself very quickly. I wonder how long it will take for the big name brands in the helmet industry to start offering competitive products. I'd bet 5-10 years from now this type of helmet will be a common item on the shelf.
Yeah super expensive, but I can't imagine how much safer it would be. That rear-view camera + HUD is brilliant.
Plus it has that amazing technology where you can switch from tinted to non-tinted shield with the click of a button. Mercedes uses that in their SL's these days.
Last edited by VicSkimmr; 08-18-2014 at 03:19 PM..
It looks better than Google Glass too. You could just get it in white and pretend to be the Stig all day.


a. 1. Without color; not distinguished by any hue; transparent; as, colorless water; a colorless gas.
Adj. 1. colorless - lacking in variety and interest; "a colorless and unimaginative person"; "a colorless description of the parade"
colorful - striking in variety and interest; "a colorful period of history"; "a colorful character"; "colorful language"


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Home Blog 'My life flashed before my eyes" – Benny Blanco recalls the awkward...
'My life flashed before my eyes" – Benny Blanco recalls the awkward moment he accidentally kissed Beyonce in front of Jay-Z
American record producer/DJ/ songwriter, Benny Blanco has revealed the awkward moment he accidentally kissed Beyonce in the presence of Jay-Z from about 10 years ago.
The "Lonely" producer, 33, did an interview with Zane Lowe on Apple Music on Wednesday Marcg 24, to celebrate the release of his forthcoming album FRIENDS KEEP SECRETS 2, the follow-up to his 2018 album.
During the interview, he shared a story about being a guest at Beyoncé's house in the Hamptons with other producers for a beat battle and accidentally kissing her.
"Beyonce had a house in the Hamptons, okay? She would invite people up there, and you'd stay there. This was so many albums ago. This is like 2011, maybe 2010. So, you're sitting there, and it's Jay-Z and Beyoncé and you're playing Would You Rather, asking Beyonce if she'd rather have constipation or diarrhea for her life. Or you're sitting there asking Jay-Z if he likes Girls, like the show Girls. One night we're chilling… This will probably get ripped down off the internet. I'm probably not supposed to say any of this. Probably going to be like a sniper who's going to shoot me through this window right now," he started narrating the story.
"But you're sitting there, and Beyoncé's like, "Let's have a beat battle." I'm sitting there. It's like me, Hit-Boy, a few other guys, and we were playing beats back and forth. I'm playing beats, and Jay-Z is there and we're just drinking, chilling. He comes up to me and he's freestyling in my ear. And I'm like, Jay-Z is sitting here, getting drunk with me while Beyonce is singing little riffs, and he's freestyling in my ear. And we're about to all go in the pool after. It's these moments, I'm like, "How is this my life?" End of the night, one night. This is the craziest story. We're sitting there. It's the end of the night. It's like the third night I'm there, okay? Everyone's drunk. We're having fun. It's the best time ever,"
he continued.
Benny then reveals that he ended up accidentally kissing Queen Bey while saying goodbye.
"We're saying, "Good night." And it's at that point where I'm like… Okay, I haven't yet. Do I hug Beyoncé? Like, what's the protocol? What do you do? Are you just like, "Bye." For the first night or so, it's like, we're not close yet. And so I'm like, "Hey, bye" at the end of the night. But it's like, we're all getting to know each other, and normally in that time I'd be like, "Ah, great to hang." So I'm like, do I go in for the hug? And you're like a little-Dude. Okay. You're with Jay-Z and Beyoncé. You're at their house. They're in shorts and a t-shirt. You're sitting there. And I remember I go in for the hug, okay? And then, I'm like, oh, I'm going to kiss her on the cheek. That's what you do. Yeah, you do. Everyone does that. Like, if I see someone… I'm very European. You go- You go in and you do that. This is years ago. I was even more European. So, you go in. And I went to do like, kiss on the cheek, and I guess we just missed a little bit. And just like, I definitely hit the corner of some sort of lip. I'm like, "Oh, my God. This is the worst thing in my life." And I'm sitting there, and as I'm doing it, out of the corner of my eye, Jay-Z is right there looking at me. And I'm just like, my lip is here. Hers is there, and there's definitely some corner things are happening."
"And I look at Jay and I'm like, "Oh, okay. I'm dead. My life is over. It was great. Nice knowing you guys." And like- This man is going to be in a coffin tomorrow. My life flashed before my eyes. And I'm sitting there, and I look. And then, he's like, "All right, bro. See you tomorrow." Like, no one noticed… She didn't… This is where my neuroses comes in. But the crazy thing is, these things … Look. You go and you look."
Benny said the music he made with Beyonce never came out but he is thankful for the experience.
"That's a situation where I never made music with Beyoncé that came out, but that moment in my life, going there, learning from them, I learned so much from her, learned so much from him. Just, that experience is the best to me. It's not about … To me, it's about the journey. Again, just about … I don't give a f-k what happens. I don't … I just got to have a coolest two months of my life."
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Fauci: US could face 'fifth wave' of Covid as Omicron variant nears
Victoria Bekiempis in New York
Collins and Fauci emphasise need for vaccines and boosters
Canada confirms first variant cases in North America
Coronavirus: live coverage
Joe Biden's chief medical adviser, Anthony Fauci, said on Sunday the US has "the potential to go into a fifth wave" of coronavirus infections amid rising cases and stagnating vaccination rates. He also warned that the newly discovered Omicron variant shows signs of heightened transmissibility.
Related: Israel seals borders and Morocco bans flights as Omicron Covid fears rise
As Fauci toured the political talkshows, countries around the world including the US scrambled to guard against Omicron, which has stoked fears of vaccine resistance.
On Sunday evening, shortly after the first Omicron cases in North America were confirmed in Canada, the White House said Biden met Fauci and other advisers on returning to Washington from holiday in Nantucket.
Fauci, a statement said, "informed the president that while it will take approximately two more weeks to have more definitive information on the transmissibility, severity, and other characteristics of the variant, he continues to believe that existing vaccines are likely to provide a degree of protection against severe cases of Covid".
The statement also said those already vaccinated should receive booster shots. Biden would "provide an update about the new variant and the US response on Monday", the White House said.
Earlier, Fauci discussed why Omicron has raised such alarm.
"Right now we have the window into the mutations that are in this new variant," he told NBC, "and they are troublesome in the fact that there are about 32 or more variants in that very important spike protein of the virus, which is the business end of the virus.
"In other words, the profile of the mutations strongly suggest that it's going to have an advantage in transmissibility and that it might evade immune protection that you would get, for example, from the monoclonal antibody or from the convalescent serum after a person's been infected and possibly even against some of the vaccine-induced antibodies.
"So it's not necessarily that that's going to happen, but it's a strong indication that we really need to be prepared for that."
Fauci also pointed to how Covid case numbers shifted dramatically in South Africa, where Omicron was discovered, over a short period.
"You were having a low level of infection, and then all of a sudden there was this big spike … and when the South Africans looked at it, they said, 'Oh my goodness. This is a different virus than we've been dealing with.'
"So it clearly is giving indication that it has the capability of transmitting rapidly. That's the thing that's causing us now to be concerned, but also to put the pressure on ourselves now to do something about our presentation for this."
The federal Centers for Disease Control and Prevention (CDC) has said no Omicron cases have been discovered in the US.
Fauci said: "As we all know, when you have a virus that has already gone to multiple countries, inevitably, it will be here."
On CBS, Fauci said any fifth wave of cases "will really be dependent upon what we do in the next few weeks to a couple of months".
"We have now about 62 million people in the country who are eligible to be vaccinated," he said, "who have not yet gotten vaccinated.
"Superimpose upon that the fact that, unquestionably, the people who got vaccinated six, seven, eight, nine, 10 months ago, we're starting to see an understandable diminution in the level of immunity. It's called waning immunity, and it was seen more emphatically in other countries before we saw it here."
Fauci said an increase in immunization rates and booster shots might prevent another surge – but the US had to act fast.
"So if we now do what I'm talking about in an intense way, we may be able to blunt that," he said. "If we don't do it successfully, it is certainly conceivable and maybe likely that we will see another bit of a surge. How bad it gets is dependent upon us and how we mitigate."
Politically charged resistance would seem to make a rapid increase in vaccination rates unlikely. While more than 70% of US adults are fully vaccinated, the most recent CDC data indicated cases up 16% over the previous week. By Sunday there had been 48,202,506 cases in the US with 776,537 deaths, according to Johns Hopkins University.
Francis Collins, director of the National Institutes of Health, also discussed the Omicron variant on Sunday.
"I think the main thing that has us focused on this," he told CNN, "… is that it has so many mutations."
Collins also said there were "good reasons to think it will probably be OK but we need to know the real answers to that and that's going to take two or three weeks".
On Friday, Biden said the US would join other countries and impose restrictions on travel from southern Africa from Monday.
Collins said: "I know, America, you're really tired of hearing these things, but the virus is not tired of us and it's shape-shifting itself. If you imagine we're on a racetrack here … it's trying to catch up with us, and we have to use every kind of tool in our toolbox to keep that from getting into a situation that makes this worse.
Related: Boris Johnson 'ignored' my plan to tackle deadly Covid variants – senior official
"We can do this but we have to do it all together."
On CBS, Fauci was also asked about Republican attacks over federal research prior to the pandemic and his role in the Trump administration.
"Anybody who's looking at this carefully realizes that there's a distinct anti-science flavor to this," he said. "They're really criticizing science because I represent science. That's dangerous. To me, that's more dangerous than the slings and the arrows that get thrown at me."
Asked if he thought attacks were meant to scapegoat him and deflect attention from Donald Trump's failures, Fauci said: "You have to be asleep not to figure that one out."
"I'm just going to do my job and I'm going to be saving lives and they're going to be lying," he said.
"If he was on my team I'd have to put hands on him," the NBA legend said of the Brooklyn Nets star's refusal to received the coronavirus shot.
Here's a look at every 2022 event announced by the MMA promotion so far
Man United XI vs West Ham: Confirmed team news, predicted lineup, Covid and injury latest for Premier League
Ralf Rangnick must decide whether to shake up his Manchester United lineup after a midweek victory over Brentford in which they were hardly convincing as his side take on West Ham this afternoon. Clearly, there's still a long way to go but United can at least take heart that their attacking players can interlink to devastating effect while live safe in the knowledge David De Gea is in the best form he's been in for years. United have confirmed Aaron Wan-Bissaka will likely miss the game through illness (though refused to confirm he was suffering from Covid-19) and that Scott McTominay should be fit for the game despite coming off injured on Wednesday.
Everything you need to know about the first UFC pay-per-view of the year


reseda noun (n.) A genus of plants, the type of which is mignonette.
noun (n.) A grayish green color, like that of the flowers of mignonette.
veda noun (n.) The ancient sacred literature of the Hindus; also, one of the four collections, called Rig-Veda, Yajur-Veda, Sama-Veda, and Atharva-Veda, constituting the most ancient portions of that literature.


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Q: How to add a "type here" message to a WPF TextBox? If the text box has no keyboard focus and no text, then show italic gray "type here" text "inside" it. How? What doesn't work:

*

*Setting the Text property - it messes up data binding.

*Overriding the template - it's messy and overridden already anyway.

Preferably, I'd like the solution to be as much XAML and as little C# as possible. Perhaps I could create an attached property that would do some magic?

A: What you're looking for is known as a Watermark.  I'm unfamiliar with WPF, but searching WPF & Watermark on "the google" returns a ton of results.

A: The best solution I've seen till now, is InfoTextBox from Kevin's WPF Bag-o-Tricks library. Check it out.

A: Create a style for your TextBox. It's one of the easiest ways to add a 'watermark' to your TextBox. The code creates a simple style and binds it to a TextBox.
(Code extracted from: http://social.msdn.microsoft.com/Forums/vstudio/en-US/d565c79e-6b4a-44e2-a566-a4a622eab22f/how-to-set-watermark-for-textbox-in-simple-way?forum=wpf)
<Window.Resources>
    <Style x:Key="MyWaterMarkStyle" TargetType="{x:Type TextBox}">
        <Setter Property="Template">
            <Setter.Value>
                <ControlTemplate TargetType="{x:Type TextBox}">
                    <Grid>
                        <Border Background="White" BorderBrush="#FF7D8683" BorderThickness="1"/>
                        <ScrollViewer x:Name="PART_ContentHost" Margin="5,0,0,0" VerticalAlignment="Center" />
                        <Label Margin="5,0,0,0" x:Name="WaterMarkLabel" Content="{TemplateBinding Tag}" VerticalAlignment="Center"
                           Visibility="Collapsed" Foreground="Gray" FontFamily="Arial"/>
                    </Grid>
                    <ControlTemplate.Triggers>
                        <MultiTrigger>
                            <MultiTrigger.Conditions>
                                <Condition Property="Text" Value=""/>
                            </MultiTrigger.Conditions>
                            <Setter Property="Visibility" TargetName="WaterMarkLabel" Value="Visible"/>
                        </MultiTrigger>
                        <Trigger Property="IsEnabled" Value="False">
                            <Setter Property="Foreground" Value="DimGray"/>
                        </Trigger>
                    </ControlTemplate.Triggers>
                </ControlTemplate>
            </Setter.Value>
        </Setter>
    </Style>
</Window.Resources>

...

<TextBox Style="{StaticResource MyWaterMarkStyle}" Height="25" Tag="Water mark"/>

A: Not the cleanest solution, but you could always add a TextBlock overlaying the TextBox and change it's Visible property when the TextBox gains or loses focus.
Nasty hack, but somewhat innovative? Do I get brownie points for that? ;-)

A: I recommend you to use Syncfusion for WPF.
It contains the SfTextBoxExt which supports watermark and other features.
Look here

redpajama_set_name: RedPajamaStackExchange


Deadly antipsychotic drugs make work easier for nursing home | Law Offices of Brian H. Fant, P.C.
On behalf of Law Offices of Brian H. Fant, P.C. on Tuesday, September 18, 2018.
Placing your loved one in a nursing home was not an easy decision. You may have tried as long as possible to be available to help your loved one at home, or perhaps you even moved him or her into your own home. However, if your loved one suffers from symptoms of Alzheimer's disease or another form of dementia, the situation likely became increasingly difficult to manage.
Whether it was an overload of little details or one terrifying moment that made you realize you were not qualified to provide the kind of care your loved one needed, you gave every effort to finding a facility that seemed staffed and capable to protect your family member. Since then, you may be noticing unsettling changes in your loved one, and it is not something you should dismiss too easily.
A recent report by a national human rights organization found that nearly 200,000 residents in long-term care facilities in Texas and across the country receive antipsychotic drugs that the FDA does not recommend for their conditions. In fact, many of the drugs have "black box" warnings because they carry a high risk for death. Nevertheless, nursing home staffs regularly use them to medicate residents whose conditions may make them challenging to manage.
You understand that the degeneration of your loved one's mental state results in behavior that is difficult to manage. This is why you opted to place him or her with trained professionals who can deal with such issues. Like other families, you may be shocked to learn that, without your knowledge or permission, the staff has dosed your loved one with medications that are inappropriate and potentially lethal.
Is there a good excuse?
Antipsychotic drugs have a sedating side effect.
Nursing homes are often understaffed, and employees do not have time to deal with the time-consuming needs of a dementia patient.
Patients taking antipsychotic drugs are easier to handle and tend to wander less frequently.
Antipsychotic drugs can bring calm to a dementia patient who is feeling agitated or aggressive.
While some of these reasons may seem like rational excuses, elder care experts say there is never a reason to sedate an Alzheimer's or dementia patient with antipsychotic drugs that pose a serious health risk. There are numerous ways to manage dementia patients, including keeping them comfortable and engaged in stimulating activities. If your loved one has suffered ill effects from antipsychotic medication in a nursing facility, you have the right to seek advice about your legal options for pursuing justice.


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The Istana Negara (Malay for National Palace) along Jalan Istana was the previous official residence of the Yang di-Pertuan Agong of Malaysia.
In June 2011, it was replaced by a new, extravagant RM800 million palace near Jalan Duta, Kuala Lumpur. So in 2013 , this lovely old Istana Negara was converted into the Royal Museum.
The history of the palace began as a double-storey mansion which called The Big House built in 1928 by a local Chinese millionaire, Chan Wing. During the Japanese occupation, it was the residence of the Japanese Governor.
When the Federation of Malaya was formed in 1950, the Selangor State Government rented the residence from the owners for Straits Dollars 5,000 a month until Malaysia reached Independence in 1957. It was then renovated to become the palace of His Majesty the Sultan of Selangor. In 1957, the owners sold the property of 13 acres to the Federal Government at an agreed valuation of Straits Dollars 1.4 Million.
The Federal Government converted the residence into the Istana Negara for the newly created sovereign post of Yang di-Pertuan Agong . Since then it has undergone several renovations and extensions. But the most extensive upgrading was carried out in 1980, as it was the first time that the Installation Ceremony of His Majesty DYMM Seri Paduka Baginda Yang di-Pertuan Agong was held at the Istana Negara.
The whole area is fenced up and the Royal Insignia of His Majesty is placed on each steel bar between two pillars of the fence. At the front of the Istana Negara, there is the main entrance which resembles an arch. On each side of the arch, are two guard posts for two members of the royal cavalry in their full dress uniform quite similar to the ones at Buckingham Palace, London. From 2013 onwards, the full dress uniform will be in Malay traditional attire as it was during the Malay Sultanate era.
In the grounds of the palace is a guard house for the members of the Royal Malay Regiment, one of the two Household Division units in the Malaysian Armed Forces (the other one is the Malaysian Royal Armored Corps Mounted Ceremonial Squadron). There is also a six hole golf course, tennis courts and a lake in the far end of the grounds.
The driveway, lined with cypresses and casuarinas, leads to two entrances – an entrance to the West Wing and the other to the East Wing.
The Istana Negara lama is now opened to public.
To see more gorgeous and beautiful photos of the old Istana Negara , do check out my friend, Tatie's blog (In Bahasa Malaysia) as she was one of the privileged few who got to go in and take photos. At other time, no photography is allowed inside the palace.....
INSIDE THE FORMER MALAYSIAN ROYAL PALACE


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Deputy Project Director, BSB Yamoussa Project
Publiée le: 17 décembre 2017
The Wildlife Conservation Society saves wildlife and wild lands through careful science, international conservation, education, and the management of the world's largest system of urban wildlife parks. These activities change attitudes toward nature and help people imagine wildlife and humans living in sustainable interaction on both a local and a global scale. WCS is committed to this work because we believe it essential to the integrity of life on Earth.
WCS in collaboration with the Ministry of Forests and Wildlife of the Republic of Cameroon, and the Ministry of the Environment and Fisheries of the Republic of Chad, under the coordination of the Commission of Forests of Central Africa (COMIFAC) has been charged with implementing the project 'BSB Yamoussa' thanks to funding from the financial cooperation of the Federal Republic of Germany (KfW). WCS is seeking a candidate for the position of Deputy Project Director, who will be based in Chad and responsible for the Chad sector of the project.
The transboundary protected area complex Binational Sena Oura – Bouba Ndjida (BSB Yamoussa), is made up of the Sena Oura National Park in Chad, Bouba Ndjida National Park in Cameroon, and peripheral areas (hunting zone around Bouba Ndjida NP, transition zone around Sena Oura NP).
Summary of Position Responsibilities:
•	The Deputy project Director is particularly responsible for management and implementation of project activities planned in the Chad sector of the project which include Park management, infrastructure development, planning, anti-poaching, community based livelihoods.
•	The Deputy Project Director reports to the Project Director.
•	Represent WCS with Chad authorities, and work in close collaboration with relevant administrations both at local and national level.
•	He/she will participate in the planning and drafting of project activities including anti-poaching, anti-trafficking outreach and support to livelihood strategies and will oversee their implementation in the project area in Chad.
•	Technical reporting and overseeing financial management
•	Assist with the recruitment and management of project staff based in Chad
Qualification requirements:
•	Strong commitment to conservation
•	Masters degree or equivalent training and experience in conservation, natural resource management and protected area management.
•	Minimum 5 years of proven track record on protected area management in Africa
•	Fluent French language skills, both written and verbal, and high level of English preferred, German also helpful
•	Ability to thrive in multicultural living and working environment
•	Willingness to live and work in multicultural environment in isolated area
Interested candidates, who meet the above qualifications, should kindly apply by sending an application letter and CV together with the names and contact information of three references to the addresses below no later than December 31, 2017. Please include "Deputy Project Director, BSB Yamoussa Project" in the subject line of your email. Send to: [email protected] and [email protected] Only short-listed candidates will be contacted for interviews.


text:
Q: soatest with maven having configuration issue I have created a new maven project and I have added soatest in it. Now when I am trying to execute the test, it seems it is deleting the workspace before executing the soatest as a result it is unable to fetch the excel datasource.
My project in jave perspective:
enter image description here
Command I am using to execute the test:

mvn clean test -Dparasoft.soatest.home="C:\Program Files
  (x86)\Parasoft\SOAtest\9.10" -Dparasoft.localsettings="C:\Program
  Files (x86)\Parasoft\SOAtest\localsettings"

my pom

A: Why do you use clean option for maven?
By default
mvn clean

will attempts to clean the files and directories generated by Maven during its build inside the target directory.
Parasoft SOAtest will not delete your workspace, but maven will do if you ask for it.