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Int. J. Mol. Sci. 2013, 14(10), 19911-19922; doi:10.3390/ijms141019911
Abstract: Diallyl trisulfide (DATS), an organosulfur compound in garlic, possesses pronounced anti-cancer potential. However, the anti-invasive mechanism of this compound in human bladder carcinoma is not fully understood. In this study, we evaluated the anti-invasive effects of DATS on a human bladder carcinoma (5637) cell line and investigated the underlying mechanism. The results indicated that DATS suppressed migration and invasion of 5637 cells by reducing the activities and expression of matrix metalloproteinase (MMP)-2 and MMP-9 at both the protein and mRNA levels. DATS treatment up-regulated expression of tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2 in 5637 cells. The inhibitory effects of DATS on invasiveness were associated with an increase in transepithelial electrical resistance and repression of the levels of claudin family members. Although further studies are needed, our data demonstrate that DATS exhibits anti-invasive effects in 5637 cells by down-regulating the activity of tight junctions and MMPs. DATS may have future utility in clinical applications for treating bladder cancer.
Bladder cancer is a prevalent malignancy worldwide and the ninth most common type of cancer. It affects three times as many men as women [1,2]. Bladder cancer presents as a non-muscle-invasive, chronically relapsing form, a high-risk non-muscle-invasive carcinoma, or a muscle-invasive form with strong potential to metastasize. High-grade non-muscle-invasive cancers frequently progress, and muscle-invasive cancers are often lethal and have the highest recurrence rate of any malignancy. Although systemic chemotherapy has improved the duration and the quality of life of patients with bladder cancer, long-term survival rates are poor, and the most common cause of mortality is recurrence with metastasis [3–5]. Therefore, development of new agents and more efficient treatment modalities for this disease are needed.
Several epidemiological studies have revealed that dietary intake of Allium vegetables is protective against the risk of various types of malignancies including bladder cancer [6,7]. Among Allium spp., garlic is a plant commonly used for seasoning food in many different cultures, particularly in Asian countries. As major organosulfur compounds (OSCs) derived from garlic, diallyl sulfide (DAS), diallyl disulfide (DADS), and diallyl trisulfide (DATS) are well-characterized flavor components. These garlic-derived allylsulfides induce cell cycle arrest and apoptosis, as well as inhibit cell invasion by many types of human cancer cell lines. Of them, DATS possesses the most potent cancer activity [8–10]. We have reported recently that DATS-induced apoptosis in human leukemia cells is mediated by the generation of reactive oxygen species (ROS) and subsequent activation of the ROS-dependent caspase pathway . In addition, DATS suppresses cancer cell proliferation and inhibits the growth of transplanted tumor xenografts by inducing apoptosis and/or by blocking abnormal cell cycle progression at the G2/M phase [10,12–16]. However, this effect is selective for cancer cells, as normal cell lines are resistant to cell cycle arrest and apoptosis by DATS [9,12]. Moreover, DATS also inhibits migration and invasion of highly metastatic colon cancer cells via down-regulation of matrix metalloproteinases (MMPs) and inhibition of the nuclear factor-kB signaling pathway .
However, no reports address whether DATS affects migration and invasion of human bladder carcinoma cells in vitro. Thus, the purpose of this study was to investigate the effects of DATS on cell migration and invasion of the human bladder carcinoma cell line 5637 and to explore the potential mechanisms of the effects. The results indicated that DATS inhibited the migration and invasion of 5637 cells in vitro and demonstrated that DATS could serve as a potential anti-metastatic agent.
2. Results and Discussion
2.1. DATS Inhibits 5637 Cell Migration and Invasion
Because cell migration is essential for invasion and metastasis of cancer cells, we first examined the effect of DATS on migration and invasion of 5637 cells. A scratch wound healing assay was used for the migration assay. The results showed that DATS significantly inhibited migration of 5637 cells compared to that of the control group in a time- and concentration-dependent manner (Figure 1B). DATS also inhibited cell invasion in a concentration-dependent manner (Figure 2A), as measured by a Matrigel invasion assay. The viability of cells grown under the same conditions was measured by the MTT assay to exclude the cytotoxic effects of DATS on 5637 cell growth. As indicated in Figure 1A, the DATS concentrations used to inhibit cell migration and invasion did not affect cell viability. These results clearly indicate that the inhibition of cell migration and invasion was not due to a cytotoxic action of DATS, and that DATS is an effective anti-migratory and anti-invasive compound in 5637 cells.
2.2. DATS Inhibits MMP Expression and Activity
One of the most important characteristics of a metastatic cell is the ability to degrade the extracellular matrix (ECM), as this enables the cell to invade through the basement membrane [18,19]. MMPs, a family of zinc-dependent endopeptidases, play a critical role in ECM degradation, which is the starting point of cancer invasion and metastasis. Among MMPs, MMP-2 and MMP-9, which are the gelatinase type of MMPs, promote tumor cell invasion in various cancer cell lines because of their capability to degrade various types of collagens [20,21]. In addition, the activity of MMPs is tightly controlled by transcriptional activation, by a complex proteolytic activation cascade, and by an endogenous system of tissue inhibitors of metalloproteinases (TIMPs). TIMPs inhibit MMPs by forming stoichiometric complexes to regulate matrix turnover [22,23]. Therefore, we determined whether or not the anti-invasive activity of DATS was associated with modulation of TIMP and MMP expression. As shown in Figure 2B,C, DATS markedly inhibited the expression of MMP-2 and MMP-9 mRNA and protein; however, the transcriptional and translational levels of both TIMP-1 and TIMP-2 showed concentration-dependent up-regulation in response to DATS treatment. We next determined whether DATS-induced down-regulation of MMP expression was associated with the inhibition of MMP activities using a zymography analysis and an in vitro matrix degradation activity assay. As expected, the gelatinolytic activities of MMP-2 and MMP-9 in 5637 cells decreased significantly following DATS treatment (Figure 3A). Additionally, similar inhibition was observed in the MMP-2 matrix degradation activity assay as well as that for MMP-9 (Figure 3B). Therefore, our results suggest that DATS induced an increase in the TIMP/MMP ratio as a key factor in the regulation of the anti-metastatic process, which subsequently blocked degradation of the ECM and lead to inhibited cell invasion.
2.3. DATS Enhances the Transepithelial Electrical Resistance (TER)
Several specialized and distinct intercellular structures in epithelial cells, including gap junctions, tight junctions (TJ), adherens junctions, and desmosomes are responsible for establishing contact between neighboring cells. These junctions mechanically link normal epithelial cells, and they generate signals that are sent to the interior of the cell to report on the extent of contact with neighbors and the ECM. Another hallmark of malignant transformation of epithelia is that these connections, particularly TJs, are lost [24,25]. In precancerous lesions of the epithelia and cancerous epithelia, TJ strands become disassembled and disorganized or lost altogether, and the TJs cause loss of cell polarity and an increase in motility and invasiveness. Thus, there is an association between the loss of cell-cell adhesion structures and metastasis in many epithelial cancers, as indicated by decreased resistance to electrical current (measured by TER) and increased markers of paracellular permeability. TER values were measured to further examine the relationship between TJ remodeling and the anti-invasive activity of 5637 cells treated with DATS. As shown in Figure 4, incubating 5637 cells with DATS concentration-dependently increased TER, suggesting that DATS increases tightening of the TJs in 5637 cells.
2.4. DATS Inhibits Claudin Family Member Expression
Many TJ proteins (claudins, occludins, and junctional adhesion molecules) are linked to the actin cytoskeleton through cytoplasmic accessory proteins to tighten the cell structure and maintain a barrier. Among them, claudin family proteins comprise a multi-gene family of 27 species and are major integral membrane proteins forming the backbone of TJs that are directly implicated in the barrier and adhesive functions of endothelial and epithelial cells . A growing body of evidence reveals the highly contextual up-regulation of claudin expression in certain cancer types, and, moreover, the relevance of claudins in promoting cancer cell invasion, and metastatic progression [27–29]. For example, overexpression of claudin-3 and -4 has been demonstrated in several tumors, including breast and ovarian cancers [30,31]; however, knockdown of these two claudins inhibits cancer cell invasiveness . Yoon et al.  showed that claudin-1 plays a causal role in acquisition of invasive capacity in human liver cells, which is associated with increased expression of MMP-2. In the present study, we found that DATS concentration-dependently inhibited expression of claudins-1–5 at the transcriptional and translational levels in 5637 cells (Figure 4B,C). However, unlike the result attained in this research, it has been reported that the increase of expression for some types of claudins can promote the increase and spread of cancer cells. For instance, when the expression of claudin-3 or claudin-4 was suppressed, it not only caused the increase and spread of ovarian cancer, but it facilitated an epithelial-to-mesenchymal transition [31,34]. Additionally, there was no significant change in TER, but there was an increased activation in β-catenin signaling or PI3K/Akt signaling. When differentiated embryo-chondrocyte expressed gene 1 (the basic helix-loop-helix transcriptional regulator in breast cancer cell) was knocked down, the invasive capacity increased. It was reported that this is associated with the increase of transcription activation in claudin-1 . Although future studies will need to clarify the precise mechanism and signal transduction pathway for the relationship between the increased TER values and claudin down-regulation, these results demonstrate that the loss of claudins contributes to TJ tightening. Furthermore, the laboratory recently utilized AGS human gastric carcinoma cells and researched the anti-invasive activity of DADS. The OSCs contained two sulfurs . According to precedent research, the suppression of invasion due to the DADS is associated with the increase of tightening in TJs, but the invasion-suppressed effects of cancer cells resulting from DATS was much more effective in the low concentration treatment group compared to DADS. Even though the types of cancer cells used in the two experiments were different, DATS had a more outstanding antioxidant, anti-inflammatory, and cancer cell extinction effect of the three kinds of OSCs. DAS presented as the lowest [9,37,38]. These results signify how the number of sulfur atoms is an important factor that decides the biological activation of OSCs.
In summary, we demonstrated the anti-invasive effects of DATS on 5637 human bladder carcinoma for the first time: (1) DATS inhibited cell migration and invasion; (2) DATS inhibited MMP-2 and MMP-9 activity and expression by up-regulating TIMP-1 and TIMP-2 expression; and (3) DATS increased TJ tightening associated with down-regulating claudin expression. Overall, our data provide a new experimental basis for the clinical application of DATS in cancer treatment.
3. Experimental Section
3.1. Cell Culture and Growth Inhibition Assay
Human bladder carcinoma 5637 cells were purchased from the American Type Culture Collection (Rockville, MD, USA) and cultured in RPMI 1640 medium supplemented with 10% (v/v) fetal bovine serum (FBS), 1 mM glutamine, 100 U/mL penicillin, and 100 μg/mL streptomycin (Gibco BRL, Grand Island, NY, USA) at 37 °C in a humidified atmosphere of 95% air and 5% CO2. The colorimetric 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) viability assay (Sigma-Aldrich Chemical Co., St Louis, MO, USA) was used to assess growth according the manufacturer’s instructions.
3.2. Wound Healing Assay
The 5637 cells were grown to confluence on 35-mm cell culture dishes coated with 20 μg/mL rat tail collagen (BD Biosciences, Bedford, MA, USA) and wounded by scraping the cells with a pipette tip. The cells were then cultured in the presence or absence of DATS in serum-free media for the indicated times. Wound closure of cells was observed and photographed under a microscope at ×40 magnification. Experiments were repeated three times.
3.3. Cell Invasion Assay
Matrigel invasion assays were used to assess the ability of 5637 cells to penetrate the ECM in the presence or absence of DATS. Briefly, 5637 cells were cultured in serum-free media overnight. The cells (5 × 104 cells) were loaded on pre-coated Matrigel 24-well invasion chambers (BD Biosciences) in the presence or absence of DATS. Then 20% FBS medium was added to the wells of the plate to serve as a chemoattractant for the cells. The cells in the Matrigel invasion chambers were incubated for 48 h. The invading cells were fixed with 10% formalin, stained with Harris modified hematoxylin and eosin Y (Sigma-Aldrich, St. Louis, MO, USA) and counted (three fields of each triplicate filter) using an inverted microscope .
3.4. Western Blot Analysis
The cells were harvested, lysed, and protein concentrations were quantified using a Bio-Rad protein assay (Bio-Rad Lab., Hercules, CA, USA), according to the manufacturer’s procedure. Antibodies against MMPs and TIMPs were purchased from Santa Cruz Biotechnology Inc. (Santa Cruz, CA, USA), and those for the claudins were obtained from Invitrogen Corp. (Carlsbad, CA, USA). An antibody against actin was purchased from Sigma-Aldrich. Peroxidase-labeled donkey antirabbit immunoglobulin and peroxidase-labeled sheep antimouse immunoglobulin were purchased from Amersham Corp. (Arlington Heights, IL, USA). An equal amount of protein was separated by 8%–10% sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and then electrotransferred to a nitrocellulose membrane (Schleicher & Schuell, Keene, NH, USA) for Western blot analysis. The blots were probed with the desired antibodies for 1 h, incubated with diluted enzyme-linked secondary antibodies, and visualized by enhanced chemiluminescence according to the manufacturer’s procedure (Amersham, Arlington Heights, IL, USA).
3.5. RNA Extraction and Reverse Transcription-Polymerase Chain Reaction (PCR)
Total RNA was isolated from cells using an RNeasy kit (Qiagen, La Jolla, CA, USA) and primed with random hexamers to synthesize complementary DNA using AMV Reverse Transcriptase (Amersham, Arlington Heights, IL, USA). The PCR was carried out in a Mastercycler (Eppendorf, Hamburg, Germany) using primers. Conditions for the PCR reactions were 1× (94 °C for 3 min), 35× (94 °C for 45 s; 58 °C for 45 s; and 72 °C for 1 min), and 1× (72 °C for 10 min). Amplification products obtained by PCR were electrophoretically separated on a 1% agarose gel and visualized by ethidium bromide (Sigma-Aldrich, St. Louis, MO, USA) staining .
3.6. Gelatin Zymography
The gelatinolytic activities of MMP-2 and MMP-9 in the conditioning culture medium were assayed by electrophoresis on 10% polyacrylamide gels containing 1 mg/mL gelatin at 4 °C. After electrophoresis, the gels were washed in 2.5% Triton X-100 for 1 h and incubated at 37 °C for 24 h in activation buffer (50 mM Tris-HCl, pH 7.5, 150 mM NaCl, 10 mM CaCl2, and 0.02% NaN3). After staining with Coomassie Blue R-250 (10% glacial acetic acid, 30% methanol, and 1.5% Coomassie Brilliant Blue) for 2 h, the gels were destained with a solution of 10% glacial acetic acid and 30% methanol without Coomassie Blue for 1 h. White lysis zones, indicating gelatin degradation, were revealed by staining with Coomassie Brilliant Blue R-250.
3.7. In Vitro MMP Activity Assay
MMP activity in the supernatant was measured using the MMP Gelatinase Activity Assay Kit (Chemicon International Inc., Temecula, CA, USA), according to the manufacturer’s instructions. Briefly, aliquots of culture media were incubated with biotinylated gelatinase substrates provided by the manufacturer to cleave active MMP-2 and MMP-9 in the culture media. The fragments were then added to a biotin-binding 96-well plate and incubated for 30 min at 37 °C to allow the biotin-containing fragments to bind to the plate while digestion continued. The digested but unbound fragments were removed by repeated washing, whereas the undigested biotin-labeled gelatinase that bound to the plate was detected by adding a streptavidin–enzyme complex that resulted in a colored product measured at a wavelength of 540 nm with a microplate reader (Molecular Devices, Palo Alto, CA, USA).
3.8. TER Measurements
TER (a measure of TJ formation) was measured with an EVOM Epithelial Tissue Voltohmmeter (World Precision Instruments, New Haven, CT, USA), equipped with a pair of STX-2 chopstick electrodes. Briefly, 1 × 105 cells in 0.5 mL of complete medium were seeded into 12-mm Transwell inserts with a membrane pore size of 0.45 μm (Corning Costar Corp., Corning, NY, USA), placed in 24-well plate containing 0.75 mL of growth medium, and allowed to reach full confluence, after which fresh medium was replaced for further experiments. Inserts without cells, inserts with cells in medium, and inserts with cells with DATS were treated. Readings were taken 2 days after seeding the cells. The TER values were calculated by subtracting the blank values from the sample values and then normalizing those values to the growth area of the monolayer.
Each experiment was performed in triplicate. Results are expressed as means ± standard deviations. Significant differences were determined using Student’s t-test. A p < 0.05 was considered significant.
In this study, we have suggested the mechanism of DATS-induced inhibition of cell motility and invasiveness in human bladder carcinoma 5637 cells. The results indicated that DATS exposure caused inactivation of MMP-2 and -9 by reducing their expressions at both the protein and mRNA levels, and the up-regulation of TIMP-1 and TIMP-2 expression. The increased TJ tightening by DATS treatment was associated with the marked inhibition of claudins, major components of TJs. Although further controlled trials are warranted, these results provide evidence that DATS inhibits the metastasis of human bladder cancer in vitro.
This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (2012-0000476) and a grant (Code #7–19-42) from Rural Development Administration, Republic of Korea.
Conflicts of Interest
The authors declare no conflict of interest.
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Renewed battle over using fetal tissue in medical research
WASHINGTON (AP) — Lawmakers clashed over science, ethics and politics at a House hearing Thursday on using fetal tissue in critically important medical research, as the Trump administration reviews the government’s ongoing support for such studies.
Research fields in which fetal tissue is used include HIV, childhood cancers, treatments that enlist the body’s immune system to battle cancer, and the hunt for a vaccine against the Zika virus, a cause of birth defects.
Republicans said alternatives to fetal tissue are available and should be used instead. Democrats said that view is at odds with science. Each side called on expert witnesses.
“Most of my constituents don’t understand when you harvest baby parts, why that is OK,” said Rep. Mark Meadows, R-N.C., who chaired the hearing by the Oversight and Government Reform Committee. Meadows, leader of the conservative House Freedom Caucus, is one of President Donald Trump’s biggest allies in Congress.
But Rep. Gerry Connolly, D-Va., responded, “The consensus in the scientific community is that there is currently no adequate substitute for fetal tissue in all of the cutting-edge research for which it is used today.”
The government has funded research using fetal tissue for decades, under administrations of both political parties. Trump has gone out of his way to court social and religious conservatives among his staunchest supporters.
The administration’s new review of whether taxpayer dollars are being properly spent on fetal tissue research has raised alarms among medical investigators, who fear their work will be stopped to satisfy anti-abortion activists.
Under Secretary Alex Azar, the Health and Human Services Department says it is trying to balance “pro-life” and “pro-science” imperatives in its ongoing audit of fetal tissue research.
Azar’s office said in a statement that the National Institutes of Health put a pause on procurement of new human fetal tissue in the fall, after the audit was announced. The department says research with fetal tissue already on hand was allowed to proceed, and that it never intended to stop research. The HHS statement left open the possibility of procuring new fetal tissue to prevent research projects from being interrupted.
Research involving fetal tissue accounted for $98 million in NIH grants and projects during the 2017 fiscal year, a small fraction of the agency’s overall research budget. NIH said that $98 million figure represents the entire budget for the grants at issue, even if only a portion of a particular grant was devoted to fetal tissue research.
HHS has not announced a timeline for completing its audit.
Fetal tissue is used to produce research mice that model how the human immune system works. The tissue, from elective abortions, would otherwise be discarded.
Biochemist Tara Sander Lee told the committee that alternatives to fetal tissue are available and can be used.
“We do not need fetal body parts from aborted babies to achieve future scientific and medical advancements,” said Sander Lee, with the Charlotte Lozier Institute, which is opposed to abortion. Tissues from infants who have to undergo heart surgery are among the alternatives, she said.
But neuroscientist Sally Temple, testifying on behalf of the International Society for Stem Cell Research, told lawmakers that alternatives to fetal tissue are simply not suitable for every disease and condition being studied.
“The consensus opinion is that those alternatives are not sufficient,” she said.
Temple explained that tissue samples from different stages of the life cycle are not interchangeable. “It is not the same material,” she said. “It is a different developmental stage. It has unique properties.”
Temple said researchers would readily use alternatives to fetal tissue if that was suitable.


An Annoying and Alarming Trend
The latest trend in dieting is alternate-day fasting, which essentially involves a feast-and-famine approach. Advocates of this method claim that it can lead to weight loss and various other benefits. However, as a physician-researcher, I find this trend both annoying and alarming. I firmly believe in the importance of sensibly consuming real foods as part of a lifelong commitment to health. Moreover, I rely on scientific evidence to guide my counseling. That's why I welcomed a yearlong study that compared alternate-day fasting with the more commonly practiced calorie restriction method.
Data and Insights
In this study, 100 obese participants, mostly African-American women without major medical issues, were divided into three groups. The first group followed an alternate fasting plan, where they consumed only 25% of their daily caloric needs on fasting days and slightly more (125% of their caloric needs) on non-fasting days. The second group ate 75% of their daily caloric needs consistently every day. The third group served as a control and ate according to their typical dietary habits for the duration of six months.
Both diet groups experienced a weight loss of approximately 5.5% of their body weight (equivalent to 12 pounds) by the sixth month. However, by the twelfth month, they regained about 1.8% (four pounds) of their initial weight. Importantly, both groups showed significant improvements in blood pressure, blood sugar, insulin levels, and inflammatory proteins compared to those in the control group.
One notable difference between the two diet groups emerged at the end of the study. The alternate fasting day group experienced a significant increase in low-density lipoprotein (LDL) cholesterol, which rose by 11.5 mg/dl compared to the daily calorie restriction group. Since high LDL cholesterol is considered a risk factor for heart attacks and strokes, this finding raises concerns.
The Real-life Implications and Limitations
While the study sheds light on alternate-day fasting, it is important to recognize its limitations. Firstly, the study had a small sample size and a relatively high dropout rate, with only 69% of participants completing the full duration. This dropout rate reduces the statistical power of the findings. Interestingly, almost half of the dropouts from the alternate-day fasting group cited dissatisfaction with the diet. In contrast, the daily calorie restriction group experienced fewer dropouts, with reasons unrelated to the diet itself.
It is not surprising that individuals disliked alternate-day fasting, as previous research has shown that it often leads to hunger and irritability on fasting days. Furthermore, participants in the fasting group tended to consume more food on fasting days and less on feasting days over time. By the end of the study, their eating patterns resembled those of the calorie restriction group.
The authors also acknowledge additional limitations. The control group did not receive any food or counseling, and they did not receive the same attention from the study personnel. These additional factors could potentially influence their results beyond their dietary choices. It is worth noting that the study did not include individuals with high blood pressure, high cholesterol, or diabetes, so we cannot draw conclusions regarding the potential benefits of alternate-day fasting for these groups.
The Bottom Line
In conclusion, rather than suggesting the need for further studies on alternate-day fasting, I emphasize the existing evidence supporting a common-sense lifestyle approach to weight loss. A balanced diet consisting of ample fruits and vegetables, healthy fats, lean proteins, and regular exercise remains the most effective and sustainable method. The variety of "real" foods available, from apples to zucchini, exceeds a hundred options that can be enjoyed while promoting weight loss.
Instead of wasting money on fad diet books or processed carbohydrates, I recommend exploring the fresh or frozen produce aisle, or visiting your local farmer's market, to embrace a healthier dietary approach. Combine this with regular exercise throughout your life, and you will be on the right track. Remember, nobody became overweight from eating broccoli. However, if you struggle with binge eating or stress-eating sugary or starchy foods and feel unable to control these habits, I encourage you to consult your doctor, as this presents a separate issue that should be addressed.
1. Effect of Alternate-Day Fasting on Weight Loss, Weight Maintenance, and Cardioprotection Among Metabolically Healthy Obese Adults: A Randomized Clinical Trial. JAMA Internal Medicine, Published online May 1, 2017.


text:
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Our commercial lyophilizers are utilized for a range of applications from tiny pilot study plants to large commercial multi-dryer industrial operations. When it comes to the dietary value of preserved food, commercial lyophilizer shines bright. It is approximated that a commercial lyophilizer can protect around 97% of the first value of a food, which means that freeze-dried food can be just as nourishing as fresh food.

domain: agronomy


text:
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We can help right away. Chat with a jewelry expert now!

domain: artistic


India-Pakistan talk: NSAs of both countries to decide if it is quick fix or honest talks
The test now rests on NSA Ajit Doval, who has agreed to become the first Indian NSA to establish a dialogue with his Pakistan counterpart.
Let’s start with January 2004, when former Prime Minister Atal Bihari Vajpayee visited Islamabad for the SAARC Summit. It was the first after the hiatus that followed the 2001 Parliament Attack, quiet back channel talks had set up the meeting, which eventually ended Operation Parakaram and unlocked the dialogue process. The magic line that did the job rested in the middle of the fourth paragraph of the joint statement dated January 6, 2004: “President Musharraf reassured Prime Minister Vajpayee that he will not permit any territory under Pakistan’s control to be used to support terrorism in any manner.”
Follow @ETDefence Twitter handle for comprehensive coverage on other buzzing Defence stories
This reopened the dialogue process, Vajpayee lost power in the next few months and this line, which was the basis to resume the dialogue process, became a number. How? All subsequent joint statements, September 2004 when Manmohan Singh met Pervez Musharraf for the first time, February 2005 when the Foreign Ministers met, April 2005 when Musharraf came to Delhi to watch an Indo-Pak cricket match and all other engagements which followed simply recalled the assurances given in January 2006 joint statement – the assurance by itself was never repeated. South Block has a perfect reason for this. Once done, why keep repeating the line? Just refer to the date. That’s how it’s done in officialese.
The only problem is that terror did not abate, it returned through the July 2006 local train bombings in Mumbai. The jury is still out on whether investigators could establish an evidence connect to Pakistan, but the fact is that was the GoI’s official stand. So, India and Pakistan go into another dialogue freeze phase. No talks, means no progress on not just peace talks, but everything else. Just a dead phone line.
So, very quickly in two months, another quick fix becomes necessary. In far-flung Havana, Cuba, on the margins of a NAM (Non-Aligned Meet) Summit in September 2006, India and Pakistan come up with the idea of an anti-terror mechanism through another joint statement that listed more dates from the past -- January 2004, September 2004 and April 2005 as a librarian’s reference to commitments made and assurances given. The new innovative fix was called the Joint Anti-Terrorism Mechanism (JATM).
Yes, saving the dialogue was important, so allowance must be given to diplomatswhomustfindwaystokeep the larger picture intact. But the problem was with reliability and credibility of these ideas, hence on the hindsight they look like quick fixes.
The JATM is the perfect example. It was coordinated by respective foreign ministries but had officials from intelligence agencies on both sides. The idea was to let spooks, cops and terror-sponsors talk directly to each other and reach some deal.
They ended up talking past each other, blaming and discrediting each other’s claims, reaching nowhere close to what the idea intended.
The Mechanism met just twice and then fell by the wayside though the peace dialogue picked up steam until November 26, 2008. The Mumbai attacks changed it all, FBI’s involvement ensured an evidenceconnect with Pakistan for the first time. US pressure was at an all time high as Islamabad was forced to take investigations further, nab and punish the perpetrators.
But within a year, another fix was attempted at another NAM meet in Sharm-el-Sheikh that sough to delink terror from dialogue. “Action on terrorism should not be linked to the Composite Dialogue process and these should not be bracketed.”
This one boomeranged politically for then PM Manmohan Singh but the principle that engagement cannot be stopped because of terrorism was not exactly thrown out of window. Pakistan made a strong case of being a victim of terror itself, which found its own resonance.
India launched a concerted diplomatic effort, inserting action against those behind the 26/11 attacks in joint statements with every important world power. It turned into a political red line on which all progress hinged. While Zaki-urrehman Lakhvi has got bail, sources say, they expect Islamabad to show some significant progress in the coming weeks on the terror front, including the 26/11 case.
While that wait continues, another fix has been found by ways of a dialogue between the National Security Advisors on terrorism. Though the idea has its origins in Islamabad, the fact that the dialogue would have had to be conducted by Sartaj Aziz who was also Foreign Minister did raise concerns with the Pakistan Military. As the role is now split and Rawalpindi has an ex-military man Lt Gen (retd) Nasir Khan Janjua as NSA, the dialogue is well on its way, starting with Bangkok. But the question remains on whether this will go down as another innovative quick-fix to resume the peace process or as a start of a new progressive engagement on terror.
The test of this now rests on NSA Ajit Doval, who has taken the onus on himself by agreeing to become the first Indian NSA to establish a formal official dialogue with his Pakistan counterpart. “Now, it should not fail,” said a South Block official.


TC VP of DP “UkrNDIV” is always aiming at ensuring the high quality of the services rendered, that is, testing of the products samples providing accuracy, credibility and objectivity of tests results in accordance with regulations and design documentation.
TC PV would not have achieved such significant results if the team didn’t consolidate their efforts to reach the goal, i.e.“to guarantee the high quality of services for its customers” by ensuring the credibility,objectivity and accuracy of test results.
Objects of experimental research of TC PV are:
-all types of main-line freight wagons;
– freight wagons for manufacturing industry;
-mainline locomotive-hauled passenger cars, diesel multiple-unit cars, electric trains, urban rail cars;
-electric and climate control equipment of the rolling stock;
-escalators and travolators;
-assembly units and components of the rolling stock;
TC PV was successfully accredited by the National Accreditation Agency of Ukraine (NAAU) for compliance with ДСТУ ISO / IEC 17025: 2006, as an independent and technically competent center.


At about 1020 eastern time, a Cessna 152 was substantially damaged in a hard landing at Ormond Beach Airport. The student pilot, who was on her first unsupervised solo, was not injured. The pilot said she had flown the traffic pattern twice, and had made two uneventful landings. During preparations for her third landing, another pilot suggested on the Unicom frequency that all aircraft switch to a different runway. The student pilot said that switching runways in flight caused confusion for her. The airplane porpoised as she was executing the landing flare and touchdown of her third landing, and she was unable to gain control. The nose gear collapsed, the propeller contacted the runway, and firewall was damaged.


text:
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domain: entertainment


text:
Chromosome polymorphism due to pericentric inversion in Zonotrichia capensis (Emberizidae-Passeriformes-Aves)
- Cite this article as:
- Rocha, G.T., De Lucca, E.J. & De Souza, E.B. Genetica (1990) 80: 201. doi:10.1007/BF00137327
- 44 Downloads
Chromosomal polymorphism involving chromosome pairs 3 and 5 problably due to a pericentric inversion is reported for 60 specimens of Zonotrichia capensis (Passeriformes-Aves). The frequency of seven different karyotypes, due to the fact that chromosome 3 is present in the 3st and 3sm conditions and chromosome 5 in the 5st and 5m conditions, and the significance of this polymorphism are discussed for the genus Zonotrichia and for other genera from the same family (Emberizidae).

domain: literature


People who live in Beverly Hills are probably better known for their glamorous lifestyles than their righteous moral compasses. Yet some financial advisors have found beneath the glossy exterior of the legendarily materialistic enclave a sizable niche of people looking to invest in line with ethical, religious or environmental beliefs.
Mary King, a Merrill Lynch vice president and wealth manager, is one of those advisors. Working out of her Orange County home and Merrill's Beverly Hills office, she serves 50 clients and manages some $250 million in assets in accordance with those clients' ethical guidelines. "I could probably expand my client base more, but I'm putting my career on cruise control right now because I have a young child," says King, whose client base consists mainly of those interested in faith-based investing.
About 400 miles up the California coast in San Francisco, Merrill Lynch private wealth advisor Hilary Giles helps people who want to invest all or part of their portfolios along environmental and social guidelines. A good number of these clients have built their fortunes in technology and biotechnology stocks, among other industries in that area. "Many of my clients drive hybrids and have solar panels on their homes, so their interest in environmental investing isn't too surprising," she says.
The notion that advisors like Giles and King have built thriving practices around values-based investing might seem at odds with their employer's recent financial woes and ethical lapses. Just two years ago, Merrill Lynch had billions of dollars in toxic debt on its balance sheet and played no small role in helping ignite the Great Recession. Stories about former Merrill CEO John Thain's $87,000 office rug and his last-minute handout of billions in bonuses while the company was struggling to survive did little to help Merrill Lynch's reputation. Soon after Bank of America acquired the company in September 2008, the bank's stock suffered crushing losses, and skeptics said that the $29 per share purchase price, a 70% premium over Merrill Lynch's pre-acquisition value, was too high for a firm with such huge liabilities.
Yet even in the heat of the turmoil, Merrill's field force tried to contain the damage its reputation had suffered among clients. "We emphasized that client assets at Merrill Lynch were safe and in no way co-mingled with the firm's assets," says Rehana Farrell, a managing director at the firm's Managed Solutions group. As for socially responsible investors' concern about Merrill's recent malaise, Farrell says, "It really hasn't been a hindrance at all. The subject doesn't come up."
Back On Track
With both the stock market back on track and real estate perking up, things have improved considerably for both Bank of America and its new brokerage. Contributing to that growth is Merrill's value investing business, which has grown steadily and become more organized over the last few years. That growth didn't start with dictates from company headquarters, but with grassroots efforts by the firm's advisors.
The most cohesive and well-organized group in the values-based investment area is Merrill's Christian Focus Group. Established four years ago by two advisors with Christian clients, it has expanded to 650 advisors throughout the country, and more than 300 of them have joined in the last year alone. Advisors in the group come from Houston, Tennessee, Beverly Hills, Chicago, Boston, New York and other areas of the country.
Besides their religious directives, these clients might also ask their advisors to take into account concerns such as the environment.
"This isn't only about Christian values, but about values in general," says Farrell. "We even have some Jewish advisors in the group who want to understand their Christian clients better."
In the last year, the firm has stepped up its efforts to educate advisors in the field about what's available to investors who want ethical, environmental or religious screens, says Jay Morrison, a vice president at the Managed Solutions group. While there are no figures on how many investor dollars are allocated to socially responsible or ethically screened investing, Morrison says that about 10% of those clients who use separately managed accounts, (those with a $250,000 investment minimum) have identified social or religious values as important. Besides the selling agreements Merrill has with some 60 values-oriented mutual funds, the company also offers socially responsible separately managed account platforms guided by religious values.
SRI clients run the gamut from small investors to the ultra-wealthy. "We have Bible Belt investors with a few thousand dollars, people with multimillion dollar accounts, and everything in between," says Farrell. "These are all people who want the opportunity to advance philosophical and moral ideals and influence outcomes through investment."


text:
BERNE – A 30-foot boat sailed off its trailer early Saturday afternoon crashing into the trees along Helderberg Trail spreading debris along the road, Albany County Sheriff Craig Apple said.
Deputies responded to a “report of a watercraft that fell off of a trailer” at 12:08 p.m. near 382 Helderberg Trail.
When the deputies arrived, they discovered the smashed cruiser resting on its port side with its bow pointed into the woods. The vessel was heavily damaged with windows popped out, the top ripped off and pieces of the boat strewn along the road.
Deputies determined that the boat came off the trailer as a result of being improperly secured.
Scott Lendin, 57, of Westerlo, was towing the boat. He was cited for having an unsecured load and an expired trailer registration.

domain: news


'They scoffed at a "Barbie" wanting to join': Blonde bombshell who enlisted in the Marines at age 19 has visited over 100 countries with the military after graduating at the top of her class
MSNBC’s Lawrence O’Donnell: ‘Donald Trump Is a Russian Operative’
"Donald Trump is a Russian operative — if tonight’s reporting by The Washington Post and The New York Times is true."
Yeah. The NYT and WaPo never make up stories, right? Must be true.
Soon they will also tell you Putin will be vice president next term, replacing Pence.
They will never end the Russia bullshit no matter how many Mueller reports, Ukraine transcripts and sanctions against Russia there are
National security official discredits New York Times report on Russia helping Trump in 2020
The older people in my high end west side LA area are starting to vent on the neighborhood board about the homelessness population, no police reaction to safety, higher taxes, misuse of taxes, safely, cost of living (insurance, water, electrical, parking meters, etc). They are overtly blaming it on the demo politicians. Police stand down on robberies. Just paper shuffle. Wait until they find out about attack on prop 13 and inheritance tax on the ballot 40% over 3.5 million.
One of the best from U2.
U2 - I Still Haven't Found What I'm Looking For
The Navy Has Installed the First Drone-Stopping Laser on a Destroyer
The logic is clear. If Sanders is now Russia's puppet, then the left must vote for Donald J. Trump.
Re-electing him is the only way to thwart Putin.
Biden’s Losing His Faculties: Says His Son ‘Was Attorney General of the United States’
Dementia Is A Cruel Disease And He Shouldn't Have To Go Through It Publicly
by Jeff Dunetz | Feb 21, 2020 | Politics
Trump: Jared Kushner is the ‘father of criminal justice reform’
A White House official on Monday sued Politico and one of its reporters over stories and tweets that he says falsely accuse him of “lying, deceit and unethical conduct.”
Kash Patel, the National Security Council’s senior counterterrorism director, is seeking more than $25 million in damages in the suit filed in Virginia. *** The drama is amazing ***
For those who have visited the lowest point on the face of the earth, Ezekiel’s end-of-days prophecy of the Dead Sea coming to life seems impossible, yet recently, scientists have been shocked to discover that the sinkholes appearing around the sea are quickly filling up with fish and other forms of life previously unseen in the inhospitable region.
Trump's new intel chief makes immediate changes, ousts top official
"Pres Trump's new acting director of natl intel, Richard Grenell, has already made major changes at the agency, including ousting the No. 2 official.
Former acting Dir of Natl Intel Joseph Maguire & his deputy, Andrew Hallman, resigned on Friday. According to The New York Times, Grenell told Hallman, who has worked for natl intel & the CIA for three decades, that his service was no longer needed. ..."
These Bloomberg signs are epic cringe.
They're designed to win over undecided Dems in the primary. However outside the leftist bubble, everyone is laughing at how bad they are.
Trump is so powerful that his opponents now try to mimic him. Even then they still fail. In this case, Mini-Mike is trying to troll like Trump, but ends up trolling himself.
@Cameron_Gray: "Indiana: A couple allegedly drove two teenage boys off a roadway because they had flags supporting President Trump attached to their bicycles
(H/T @JackPosobiec RT )
South Korean 'Cult' Linked to Coronavirus Outbreak
The group is an offshoot of Christianity founded in 1984 by a man claiming to be a prophet sent by Jesus Christ
Masked anti-Trump protesters were arrested in Colorado Springs. Some of them had been blocking the street to protest the Trump rally.
Pretty impressive, as I wasn't aware that Grindr would work in China. They block a whole lot of western sites.
@JackPosobiec RT: "A 4chan user spoofed his location on Grindr to China to talk to people in Wuhan and ask them what is really going on over there and obtain accurate death counts
Is 4chan America’s leading intelligence agency?"
Those who label words as violence do so with the sole purpose of justifying violence against words.


A must have first dress for every mini girl! This dress is made with an envelope neck to provide a larger neck opening to make changing your newborn a breeze. Pair this dress with a pair of leggings, tights or bloomers.
- GOTS 100% Organic Cotton
- Ethically Produced
- Machine Wash Cold
Please allow 2-3 business days to process your order. Final sale.


text:
Thomas Toppler, born 1985, started
to play the drums at the age of 6 and
began his studies at the University of
Graz in Austria at the age of 14.
Thomas completed his degree in
Classical Percussion and has since
played with many different Orchestras
worldwide, including the Vienna
Symphony Orchestra, Chamber
Orchestra Vienna, Volksoper Wien and Concentus Musicus.
He is also a founding member of The Erlkings


text:
We served tea sandwiches, asparagus and mushroom tartlets, proscuitto wrapped cantaloupe, fruit cups, cake, raspberry white chocolate chip mini scones and macarons.
my friend over at Pickwick Baking made the scones and macarons. YUM!
My friend's sister made the cake. Isn't it great?
I had the diaper cake made by a great place on etsy (here)
and the sock monkeys came from Amazon. We just added the teal ribbon collars :)
My friend found this little notebook (for baby advice) in the $1 bin at Michaels. We just added the monkey from the invitations (found here).
These are the cookies I made as favors.
And here the cookies are all packaged up. :)

domain: hobby


text:
Vegan food company an Irish success
01 Jul 2020 By Jodie Gilpin
What’s in a name for plant-based food retailer? Fiid ‘kissed a lot of frogs’ before finding success
New Frontiers Alumni Shane Ryan launches his new product range FIID:
Click here to read the Sunday Business Post Article.
Inaugural European University General Assembly takes place in Ireland hosted by TUS
16 Nov 2021

domain: food


text:
Photo by Chelsea Kyle, Food Styling by Olivia Mack Anderson
There may be more sauce than you need to serve with the chicken. Use the leftovers on mashed potatoes or simply freeze for another time.
- 4–6 servings
- Active Time
- 45 minutes
- Total Time
- 1/2 hours
- 1/4 cup vegetable oil
- 1 (3 1/2- to 4-lb) free-range chicken, cut into 8 serving pieces
- 2 teaspoons salt
- 1 teaspoon black pepper
- 3/4 cup plus 2 tablespoons all-purpose flour
- 3 carrots, chopped
- 2 onions, chopped
- 5 garlic cloves, chopped
- 2 cups heavy cream
- 1 1/4 cups dry white wine
- 1/4 cup fresh lemon juice
- 1/4 cup Dijon mustard
- 1 teaspoon fresh thyme leaves
- 1 Turkish or 1/2 California bay leaf
- 1/2 cup water
- 3 tablespoons unsalted butter
- Put oven rack in middle position and preheat oven to 500°F.
- Heat oil in a 12-inch heavy skillet over moderate heat until hot but not smoking. While oil is heating, sprinkle chicken with 1 teaspoon salt and 1/2 teaspoon pepper, then dredge, 1 piece at a time, in 3/4 cup flour (total), knocking off excess. Brown in 4 batches, turning over occasionally, until golden, 5 to 6 minutes per batch. Transfer to a platter as browned.
- Stir together carrots, onions, garlic, cream, wine, lemon juice, mustard, thyme, bay leaf, and remaining teaspoon salt and 1/2 teaspoon pepper in a 5- to 6-quart heavy pot, then bring to a gentle boil over moderate heat, stirring occasionally. Add chicken (chicken will not be completely submerged) and partially cover pot, then braise in oven 25 minutes.
- Reduce oven temperature to 350°F and braise 20 minutes more. Transfer chicken to a clean platter and keep warm, loosely covered with foil.
- Pour cooking liquid through a sieve into a bowl, discarding solids, then stir in water. Melt butter in a 2 1/2- to 3-quart heavy saucepan over moderately low heat, then whisk in remaining 2 tablespoons flour and cook roux, whisking constantly, 3 minutes. Add cooking liquid in a fast stream, whisking vigorously, then cook at a bare simmer, whisking constantly, 5 minutes.
- Serve chicken with sauce.


text:
by Robert Vivian, from his collection of essays, Cold Snap as Yearning (University of Nebraska Press, 2002). photos by me.
…I went out the garage and, where the door lifted, met a foot of snow shelved perfectly crystalline and pure, as cut off from its natural bent as I was. I stared at it long enough to notice its perfect glazed angle, the weightlessness of its glide, like a different kind of wave caught midsurge before it crested, arched where the pearl white of drift was severed by the metal dungeon of the garage door. Humbled, I stepped clean over it before the door closed behing me without a sound except the pulling groan and settle of its chain.
I trudge across an open field that is endless for its blankness, each rabbit hole or declivity settled over in one smooth curve. My breath blossoms raggedly in the air, a ring of ice forming where my mouth is covered by wool.
The earth lifts before me like a great veil of white holding up its immaculate vision, a table set with fine white linen as far as I can see, except the trees that rattle and shake their brittle arms. I am a speck on the board, a tiny insect making its way over a blown anthill. At eight I am looking for God, or what passes for divinity in blown snow and nothingness. I walk on and on, the crunch of my boots magnified in the cold.
Where I am going is difficult to say. Each boot comes down in a place not touched before. I move off into another distance. I notice my breathing, the buffeted feel of my body against the cold. The wind holds me, then pushes against me form all directions, as I sway like a staggerer lost to visions of wagons going by. The world has shut down and thrown away the keys. The earth has stopped pretending, the owls have stepped over the last bones of the field mice. I am marching toward eternity in a suburban neighborhood that is no longer well kept and friendly: it is an outpost winnowed out of the cold wind, plopped randomly here in the snow in the middle of the plains…
…I am eight years old and know nothing, and it takes my breath away; and then something is revealed to me in the cusp of cold wind through branches, though I cannot say what it is. Silence and cold and wind blowing, the via negativa of coming briefly to the end of my chain, not straining at all in felt emotion: the zero where I become nothing in watching the blanked-out sky, the whisper of the wind through branches that are the difference between seeing and being.
Then it is over…Whatever I was looking for was lost long ago. Whatever I find is gone the moment I find it. Whatever I love is with me always.


text:
Welcome to South Dakota!
The service industry of retail, health and finance is one of the state’s largest economic contributors. In the rural areas, agriculture is very important. Tourism and gambling, especially at Mt. Rushmore and Black Hills sites, are also huge sources of income in South Dakota. Let’s not forget that within the Black Hills, you will find the country’s leading gold mining center.
Due to its proximity to Canada to the north and its rocky land masses and sweeping plains, South Dakota’s climate includes four distinct seasons, ranging from extremely cold, dry winters to hot and semi-humid summers. Because of its varying landscapes, you can travel to different regions of the state and experience different weather conditions.
Ranked #1 in “Business Friendliness”, South Dakota is an ideal place for business opportunities. Come be a part of the American journey and take your business to the next level while experiencing the State’s serenity, wide-opened spaces and awe-inspiring beauty.
Major cities in South Dakota include Sioux Falls, Rapid City, Aberdeen, Watertown, Brookings, and Mitchell.

domain: economics


Less equipment for more money is hardly a new concept in the car industry. Numerous lightweight specials over the years have been sold at a premium, and the genre has enjoyed something of a renaissance in recent years, too, with manufacturers realizing that a market exists for simpler, more analog cars at a time of radical technological advance: see Porsche 911 R, Aston Vantage V 12 S manual, Audi R8 RWS and so on (the latter not even more expensive, granted).
One manufacturer yet to embrace the trend is BMW, with M cars now heavier and more complex than they’ve ever been. Even M2 Competition, one of the best in the latest history, is heavier than the standard M2 because of its fresh engine. However, that may all be about to change with the next generation of M3.
If Car is usually to be believed, there will be a ‘Pure’ version of the upcoming car, available exclusively with a manual gearbox and rear-wheel drive, while the regular model gets all-wheel travel and an automatic transmission as standard. While that might seem a wee bit cynical, it might also become the best way of preserving right-drive and the fast-fading prospect of the third pedal.
Think from the 911R argument: if options like the single-mass flywheel, manual gearbox, titanium exhaust, and 500hp GT3 engine were quietly introduced to the Carrera choices list, they might possess received quite the same attention as a bespoke, stripey, homage-happy model. Manual M3s have got not really been popular with brand-new buyers ever since any kind of automatic offers been obtainable – look at how many SMG E 46s are still around – therefore the logic of combining the option with a designated trim level makes sense.
The early intel also suggests that the Pure M3 and M4 will possess less power than the flagship version — 460hp against 480hp – and probably reduced torque as well because BMW doesn’t have a manual that can handle even more than 480lb ft. The 3. 0-liter straight six will become bolstered with water injection such as the Yards 4 GTS and renamed because ‘S58’, said to end up being the most sophisticated inline 6 BMW has ever made.
The regular M3 is definitely thought to inherit a version in the M xDrive all-wheel get from the M5, along with an eight-speed auto replacing the DCT — BMW having hinted previously at automatics taking the place once occupied by dual-clutches. Expect acceleration and lap times to improve with the additional ratio and traction, with the Pure – or whatever its production name is usually – there to cater for those who feel the M3 is definitely all getting a bit much.
The following generation of M3 and M4 can be due in Frankfurt in September, BMW naturally using its home show to make the big reveal. Naturally all, of this can be informed conjecture intended for now, though rumours of any rear-drive only, manual-only M3 ought to appease those who experience AS BMW HYBRID have got abandoned their illustrious heritage to some extent. With a dedicated model, they might even put the effort into making the manual nicer to use – let’s wait and observe. And hope. More news no doubt pursuing soon!


text:
We have added famous Abbey map to the CTF map rotation by request.
Because we thought this map is too small for CTF play, we haven’t put this map on CTF rotation.
We are worrying that some players might block the exit of spawn room or narrow paths.
Actually, on TDM, we have received a report that someone had blocked the exit of blue spawn room intentionally.
(We have already banned him)
Anyway, we will try and see what happens a little more.


text:
Herbert Jefferis Pennock (February 10, 1894 January 30, 1948) was an American professional baseball pitcher. He played in Major League Baseball from 1912 through 1933. He is best known for his time spent with the star-studded New York Yankee teams of the mid to late 1920s and early 1930s. He batted and threw left-handed.
Contributions by Muboshgu, Soxrock, and McGrupp10799.

domain: history


text:
Thomas Sabo Bead Lion
- Expressive look
- Filigree design
- Powerful animal Strength and courage: this lion’s head bead should transfer its positive characteristics to the wearer. Please note: This Bead cannot be combined with the following article: KH0001
- Material925 Sterling silver, blackened, cold enamel
- Stoneszirconia black
- Colourblack, silver-coloured
- Heightapprox 1,32 cm
- Widthapprox 1,15 cm
- Item codeK0245-691-21
(For Demonstration purpose only)
925 Sterling silver
For its jewellery items, THOMAS SABO uses the highest-quality and most popular alloy in the jewellery sector: 925 Sterling silver. This is nickel-free and thus suitable for wear by allergy sufferers.
Zirconia (imitation diamond)
Zirconia is an artificially manufactured stone. It offers high scratch resistance and is shaped using a brilliant cut of the sort typical for diamonds. This provides its characteristic, dazzling look.

domain: design


Ondo State governor Rotimi Akeredolu has disclosed that he made a wrong choice by picking Agboola Ajayi as his running mate in the last governorship election.
Akeredolu said this Sunday in Igbekebo, the headquarters of Ese-Odo Local Government Area during his “meet the delegates” tour ahead of the Monday governorship primary election of the All Progressives Congress (APC).
He said despite the criticisms and attacks from various quarters alleging that Ajayi, who recently defected to Peoples Democratic Party (PDP), is his cousin, he felt that he had made a choice but a wrong choice.
According to him, he was happy that Ajayi showed his true colour at this period. He described his exit from the party as a cleansing for the better performance of the party.
Akeredolu thanked members and leaders of the party in Ese-Odo for standing firm and not leaving the APC with Ajayi, adding that it showed that his…
Source: Guardian Newspaper


text:
You can never go wrong with adorable ghosts, especially glow-in-the-dark ones! This crewneck is perfect for haunted houses, pumpkin patches, and anywhere dark so you can show off your glow.
- Sizing is UNISEX. Ladies: size down for a regular fit, order your normal size for a loose fit, size up for an oversized fit.
- Model is 5’5” and normally wears a Women’s Medium. Model is wearing a Unisex XL for an oversized fit.
- See photos for a size chart with measurements.
Additional Product Details:
- Color is black.
- Crewneck is embroidered and design glows in the dark.
- 50% cotton/50% polyester fleece blend. Very soft and comfortable feel.
- Double-needle stitching throughout for added quality.
There are no inquiries yet.


text:
Are you ready for canal rock? Alice McLaughlin recently joined the London houseboat community and with every day seemingly producing another hopeful lady with tender insights and guitar, she needs something to set her apart. Here she depicts a potential lover who has built a boat out of a lady’s hair. Rivulets of guitar, a pulsing drum machine and low-level siren create an uneasy mood, and there’s a rampaging fiddle heightening the turmoil at the end.
Review: Alice & The Majesty - I Could Love You
Are you ready for canal rock?


text:
Offering piano lessons on a one-to-one basis, taught in English.
Piano instructor with over 30 years of teaching experience. Well-versed with the ABRSM (Associated Board of the Royal Schools of Music) UK syllabus. I am equally proficient with higher grade students as well as beginners. I also enjoy teaching music theory.
My qualifications include: LTCL, FTCL, B. Music (University of Arizona, USA) I have taught in the US, Malaysia and Hong Kong.
I am also a solo pianist with over 30 years of playing experience. My repertoire is wide and varied, ranging from light classics to Jazz standards and Contemporary. I play at hotels and other social events.


text:
Features:Small body with 10000mAh large capacity. The super compact design makes it very convenient to carry aroundJust plug in and the phone will be charged, no need to worry about cables anymore (type c port devices)3 Outputs, it can charge 3 devices at the same timeDigital display screen to show ..
46+ Hours of Extra Power
Charge the Latest iPhone From 0 to 50% in 30 Mins
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Product name: Chinen Series 20W+22.5W Outdoor Power Bank with LED Light
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Features:USB-C 18W two-way fast chargeCan charge three devices at the same timeHigh quality lithium ion polymer batteryIntelligent adjust power outputDouble pressure for low power chargingSpecification:Brand: XiaomiBattery capacity: 20000mAh 3.7V (74W)Battery type: Li-polymer BatteryRated power..
Mini and Compact: Fit right into your hand, easy to carry around22.5W Super-Fast Charging: Compatible with Huawei 5A 22.5W super fast charge, and in QC, PD, SCP, FCP, AFC certified, fast charging for Huawei, for Xiaomi, for Samsung phonesSimultaneous Charging for 3 Devices: 3 devices charging at the..
Lesu Series 2A Cabled Power Bank 10000mAhCapacity: 10000mAhType-C input 5V-2AUSB1 output 5V-2ASize: 142*68*20mmBattery display: LED digital displayModel: RPP-93Rated capacity: 6250mAhMicro input 5V-2AUSB2 output 5V-2AWeight: 230g..
Features:Two-way fast charge: QC input 18W, PD output 20WTwo-port input, three-port output, can be used by several people at the same timeFast charge icon + digital display design, clear and accurate battery power displayUltra-thin 12.48mm power bank, comfortable to handle, easy to carry2USB + 1Micr..


Ruffle trim traces the split neckline of this fuchsia blouse, accentuation the femininity of the puffed-shouldered silhouette. Lightweight and airy with a softly crinkled texture, the style works equally well tucked into a pair of jeans or a skirt.
- 100% Polyester
- Hand wash cold
- Shown in XS
- Runs true- XS=0, S=2-4, M=6-8, L=10


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A different Antibiotic Exits the Consumer MarketTequin, an antibiotic which might bring about significant blood sugar troubles, is becoming pulled from the marketplace by manufacturer Bristol-Myers Squibb.
In February of the yr, the U.S. FDA expected amplified warnings within the label with the drug. It's most unsafe to diabetics, the aged, and those with kidney condition.
A Remember Urged
However, even though Bristol-Myers Squibb will quit earning and offering the drug, available shares will not be recalled.
There are already twenty deaths and more than one hundred fifty hospitalizations connected to Tequin considering that January 2000. The public curiosity group Public Citizen has petitioned for that drug to get fully recalled from the marketplace.
MSNBC May one, 2006
Dr. Mercola's Remark:Right after much information with regards to the deadly results of your antibiotic Tequin previously this year, the drug is finally staying pulled from the industry, at least partially. Ideally, the initiatives by Community Citizen should help get this fatal drug off the industry fully.
The vast majority of health and fitness harm attributable to Tequin could have been avoided if folks recognized that antibiotics are usually broadly overused. Like a make a difference of simple fact, two away from 3 babies obtain antibiotics by their initial birthday.
Ought to antibiotics be employed in any respect? Totally. I am not against their use in every circumstance, only towards the reliance on them in scenarios the place They may be of course of little if any use. As well as in my knowledge, which is effectively above 95 % of the time They are really prescribed.
When you imagined that pulling prescription drugs off the marketplace can be a uncommon party, you may review one other sixteen medication that were pulled since I have been publishg the e-newsletter.
* Vioxx. The king of withdrawn prescription drugs and very well documented in earlier chapters for causing sixty,000 deadly heart assaults and strokes and as numerous as a hundred and sixty,000 coronary heart attacks and strokes all by alone.
* Bextra Related drug to Vioxx, withdrawn for comparable explanations.
* Rezulin: Presented quickly-track acceptance from the Food stuff and Drug Administration (FDA), Rezulin was connected to 63 confirmed deaths and doubtless hundreds additional. "We've genuine trouble," a Food items and Drug Administration (FDA) medical doctor wrote in 1997, just a few months just after Rezulin's approval. The drug was not taken off the marketplace till 2000.
* Baycol (produced by Bayer AG) - a cholesterol-reducing drug taken by 700,000 People - was pulled off the market on Wednesday, August 8th. It were connected to 31 U.S. deaths. A minimum of 9 much more fatalities overseas are acknowledged.
* Lotronex: Versus considerations of 1 of its own officers, the Foods and Drug Administration (FDA) authorised Lotronex in February 2000. By the time it had been withdrawn nine months later, the Foodstuff and Drug Administration (FDA) had acquired experiences of 93 hospitalizations, a number of crisis bowel surgeries, and five deaths.
* Propulsid: A major-promoting drug for a few years, this drug was connected to many hundreds of instances of heart arrhythmias and about 100 deaths.
* Redux: Taken by numerous men and women for weightloss following its Optimizacija sajta approval in April 1996, Redux was shortly associated with coronary heart valve damage as well as a disabling, normally lethal pulmonary condition. Taken off the marketplace in September 1997.
* Pondimin: A ingredient of Fen-Phen, the diet plan fad drug. Permitted in 1973, Pondimin's link to heart valve hurt in addition to a lethal pulmonary disorder wasn't regarded till shortly just before its withdrawal in 1997.
* Duract: This painkiller was taken off the marketplace when it had been connected to significant, from time to time lethal liver failure.
* Seldane: The us's and the world's leading-offering antihistamine for a decade, it took the Foodstuff and Drug Administration (FDA) five yrs to acknowledge that Seldane was producing cardiac arrhythmias, blackouts, hospitalizations, and deaths, and another eight years to take it off the market.
* Hismanal: Authorized in 1988 and soon recognized to trigger cardiac arrhythmias, the drug was ultimately taken off the market in 1999.
* Posicor: Utilized to treat hypertension, the drug was linked to lifestyle-threatening drug interactions and greater than 100 deaths.
* Raxar: Linked to cardiac toxicities and deaths.
* Cylert FDA received thirteen experiences of pemoline-involved hepatic failure bringing about liver transplantation or Demise, symbolizing an incidence fee 10 to 25 times greater than that of the final inhabitants.
* Palladone Withdrawn resulting from a substantial chance of accidental overdose when administered with Liquor
* Tysabri Was anticipated to become the globe's top treatment for MS, but was pulled from the industry after a patient died from the exceptional central nervous method an infection.So Exactly what are Your Options to Dangerous Medicine?
Most of the time, you'll want to bolster your immune technique using the most effective and many all-natural solutions:
* Consume a healthy diet regime based on Your entire body's special metabolic style.
* Decrease, While using the intend to reduce, your consumption of sugar and grains.
* Get the ideal volume of sleep.
* Tackle anxiety properly by Understanding an energy psychology Resource just like the Psychological Freedom Procedure.Should you utilize these Fundamentals Your entire body has no option but to remain healthy and recover. It is Optimizacija za pretrazivace actually my robust perception and frequent observation in my clinical exercise that every of us is furnished with a massive array of biochemical mechanisms which can be built to deliver well being.
Many of us really have to frequently violate these rules for quite some time just before we experience the fruits of our harmful decisions.

domain: health


text:
IBT-AU Have Twitter, Follow Pope Francis, Receive Church Absolution, Pardon, Forgiveness from Sins During World Youth Day 2013, An Act of Many Firsts
Pope Francis has led what could be the largest inter-faith rally against the planned U.S. military strike launch on Syria. At least 100,000 attended the peace vigil he had called on Saturday in Rome.
Spending most of the four-hour Syria peace vigil in silent prayer, Pope Francis plead on global leaders to always strive for peace and condemn "the idols of dominion and power," tools which effectively destroy God's creation through war.
"This evening, I ask the Lord that we, Christians, and our brothers and sisters of other religions, and every man and woman of goodwill, cry out forcefully: Violence and war are never the way to peace!" he said.
"May the noise of weapons cease!" he said. "War always marks the failure of peace, it is always a defeat for humanity."
Before the start of the vigil, the gathering emitted a political tone when anti-war protesters joined the vigil attendees, waving banners that read "Don't attack Syria" and "Obama you don't have a dream, you have a nightmare." Others waved Syrian flags as well as a few rainbow "Peace" flags.
"This is already a success, the fact that all of us are here, Hindus, Christians, Buddhists, atheists," a Hindu believer named Anata told AP. Pilgrims "made an effort to fast, not to do many things, and come here from all over Italy and Europe. This is already a success."
In the U.S., specifically in Washington, 150 protesters demonstrated in front of the White House to voice their opposition to a U.S. military strike in Syria. Similar anti-war protests were also held in other parts of the country, such as in Times Square in New York City. A prayer vigil in Boston was likewise held.
In Argentina, Pope Francis' home country, inter-religious groups and human rights conducted a vigil in Plaza de Mayo in Buenos Aires as well as in other cities across the country.
Similar peace vigils were also held in Italy and in Cuba.
A number of Syrian Christians, right in the center of battle-stricken Damascus, attended a service in al-Zaytoun Church, presided by Greek Catholic Patriarch Gregorios III Laham of Antioch and All East.
"This is the start of the victory," the AP quoted him as telling the Damascus faithful. "No to war. Yes for peace."
"When man thinks only of himself, his own interests and places himself in the centre, when he permits himself to be captivated by the idols of dominion and power, when he puts himself in God's place, then all relationships are broken and everything is ruined," Pope Francis said. "Then the door opens to violence, indifference and conflict."
The Roman Catholic spiritual leader reminded everyone of Cain's famous question to God - "Am I my brother's keeper?"
"Yes, you are your brother's keeper! To be human means to care for one another," Pope Francis said.
"We bring about the rebirth of Cain in every act of violence and in every war," he said. "All of us!"
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domain: sociology


text:
DescriptionTilly wonders what to do when the TV is turned off. A whole new world is opened up for her when a little bird helps her discover the garden is one big toy box. Nature's Toy Box is an uplifting book which shows an emotional journey from boredom to adventure and the ability of a young girl to lose herself in a world of nature and imagination.
4 March 2021
Earn By Promoting Books
Earn money by sharing your favourite books through our Affiliate programme.Become an Affiliate

domain: library


text:
Radiotherapy aims to delivery a high dose of ionizing radiation to the tumour while minimizing irradiation of surrounding healthy tissues. In sites affected by respiratory motion, precise dose delivery is challenged by the motion of the tumour. To compensate for the tumour motion it has been proposed that the radiation beam be adapted in real-time to follow the tumour.
The goal of this project is to evaluate a previously developed respiratory-phase adapted radiotherapy technique. Evaluation of the technique will be performed by simulating delivery to computational patient phantoms for a variety of tumour sizes, tumour locations, and respiratory patterns. The simulated delivered dose will be compared with that obtained for conventional delivery methods.
Prospective students should be comfortable with basic programming tasks.

domain: medical


Above The Clouds Turin Brakes
I love this song went to see turin brakes not long ago amasing! wanted 2 learn this so i sat down looked onlne found it was in D and throught id figure out the rest! so thats to the person who tabed the intro out! i figured this out for my missis! so play it to you missis its a lovley song :) main riff is: D, D/F#, G D/F# is the chord D with the root note of F# so: e 2 B 3 G 2 D x A x E 2 use thumb to hit f# on the E string! One, two, three, four D, D/F#, G D, D/F#, G Up above the clouds, it is always a blue sky D, D/F#, G D, D/F#, G Some will try to trick, but you just look them in the eyes D, D/F#, G D, D/F#, G What will they do, when the money runs dry? D, D/F#, G D, D/F#, G Where will they go, when the jet planes can't fly? C G D D/F#, G When all is said and done I will love----] you---] (words sustained) C G D D/f# G When all is said and done I'll still love---] you----] D, D/F#, G x2 Starring out at the stars, you feel helpless and so small Nothing but closed down bars, no one helps you when you fall One day this world will be returning to this prime We'll all be gone, there'll be no more roads to find When all is said and done I will love you When all is said and done I'll still love you Em The rain came again, Em D D/F# G Cleaning the dream and it always makes me cry---], oh my---] Something about the rain, it sends memories through my veins Memories always stain, you can't wash them down the drain Where will I go when my broken body dies? And what will I know when I look up to the skies? When all is said and done will you love me? (x2) from G go:- e 3 2 0 E 3 2 0 at the same time in the formation of G you you cant do that then just follow it on the E string not the little e string! (Em same as before!) The rain came again, cleaning the dream And it always makes me cry, oh my Up above the clouds, it is always a blue sky - Tabbed my me! Joey!
This song is displayed as text-only. Transposing and tuning is only available for chordpro-songs.


Nummer’s raw drum work, emotive atmospheres and enigmatic collages present a bold debut. Stream the EP and watch ‘Ethereality’ music video.
ItaloJohnson announce their 8th release
ItaloJohnson‘s identity is yet to be revealed, and perhaps it never will. With this they retain simple principles in their sound design and philosophy and their 8th
Rezzett returns to The Trilogy Tapes with ‘Zootie’
Following Rezzett’s debut self titled EP, released in 2013 on Will Bankhead’s Trilogy Tapes imprint, the label has uploaded a new track by Rezzett to their Soundcloud page entitled ‘Zootie’.
Joshua Eustis of Telefon Tel Aviv announces new ‘Sons Of Magdalene’ album
Joshua Eustis, of Telefon Tel Aviv, has revealed details about his forthcoming 9 track album ‘Move To Pain‘ under his new guise ‘Sons Of Magdalene‘. Following
Farben Presents James DIN A4 – New Album Out In April
Farben has announced the release of his new 10 track album ‘Farben presents James DIN A4’ to be released on 18th April 2014 via his Fatiche imprint.
John Roberts To Release ‘Ausio’ EP On Dial
John Roberts returns to Dial Records with ‘Ausio’, his fourth EP for the Berlin based record label. ‘Ausio’ features three tracks that display a slight step away
Sula Bay: Odabo EP
Welsh born Sula Bay’s debut EP throws us deep into the mind of a 19 year-old girl living in London. With a passion for experimentation and the overt desire to express through sound, Sula’s music contains poetic mutterings of past and present experiences, coupled with purposefully disorientated synths.
Raster-Noton To Release Kyoka’s New Album ‘is (Is Superpowered)’ In May
From Tokyo to Berlin via L.A., Kyoka‘s glitch and techno indebted experimentation finds its spiritual home on Raster-Noton. Following up on 2012’s ‘iSH’, also on r-n,
Circuit Diagram Release Follow Up ‘Motown’ EP On No Counter Records
Circuit Diagram are a live act and production duo fusing hypnotic psychedelic and krautrock tendencies with live drums and electronics.
SBTRKT Announces New Instrumental Project ‘Transitions’ On Young Turks
Today SBTRKT announced the launch of his new musical project ‘Transitions’, a collection of six instrumentals written and produced over the past year that reference the creative
Irish Record Label ‘Mines Clarence’ Launches With Übung Rashida EP
The debut release of Mines Clarence comes in the form of a four track EP by Wicklow producer Ubung. With warm and dubby house vibes the
Roman Flügel & Robag Wruhme Remix DJ Koze
Following remixes from Matthew Herbert and Efdemin, Pampa Records serve up the second instalment of remixes from Roman Flügel and Robag Wruhme. Words below are by Joey Hansom: First up
Minor Science To Release ‘Noble Gas EP’ via The Trilogy Tapes
London based record label The Trilogy Tapes, run by Will Bankhead (perhaps known his design work on the Honest Jon’s and Mo Wax’s sleeves), began life
Label Debut: Gauss ‘Braunschweig EP’
New label ‘Gauss‘ is set for its first release next week and gets the label off to a flying start. Inspired by the mathematic works of


text: This pilot project aims to determine the interplay between arsenic‐induced redistribution of DNA methylation sites and NRF2 activation, and how these interactions promote the associated cellular transformation. The completion of this project will not only provide a better understanding of the roles of NRF2 in arsenic‐ induced cellular transformation, it will also provide insights into how NRF2 induction by chemopreventive compounds differs from that by carcinogens. The project exploits the latest in genomic techniques to perform high‐resolution characterization of NRF2 binding sites. The requested funds will be used for the following experiments to generate preliminary data for the proposed project: 1. Model arsenic-induced cellular transformation in vitro and run a parallel control experiment using sulforaphane in place of arsenic. 2. Perform chromatin‐immunoprecipitation‐exonuclease‐sequencing (ChIP‐ Exo‐Seq) and bisulfite sequencing on the arsenic transformed and the passaged matched sulforaphane treated cells, to identify NRF2 targets that are specific to each of those NRF2 inducers. 3. Perform molecular validations (qPCR, bisulfite‐PCR‐sanger sequencing, and luciferase reporter assay) on the identified sulforaphane specific and arsenic specific NRF2 targets. An R01 (ES 024846-01; “The interplay between NRF2 activation and DNA methylation change in arsenic-induced carcinogenesis”) was reviewed and additional preliminary data are required to support a resubmission.

domain: chemistry


text:
Welcome to Burn City Disco Thirteen!
It's simple, we want to disco and you want to disco so - LET'S DISCO!
$15 - On the door all night long
For this edition Burn City Disco present to you Disco Derby!
All your favourite resident disco DJs will be playing back to back and versing each other in a disco battle royale. This will be one for the history books!
DJ Mitchell Gee VS Lachie Spurling
Dan Bentley VS Asher Jonas
Stevie H VS Jim Paradise
The MilkMan VS Mick Bowl
Finn OD VS Billy Sun
Followed by Discovery - A Disco Recovery!
We encourage you to be yourself and to have fun. The dress code is YOU so wear what makes you happy and let's dance!


Source: Vientiane Times
Champassak provincial authorities will soon order an inspection of Road No. 16 including accurate details on the construction budget as the government contemplates plans to purchase the project rights from the private construction company.
The government signed a concession with Duangdy Bridge-Road Construction Company allowing the company to collect fees for a period of 45 years. Yet road users are not happy about the tolls being collected on this road, which they say are relatively expensive. There are two points for collecting tolls, according to an official.
The Prime Minister’s Office issued a notice recently requiring the Ministry of Public Works and Transport to set task force team with related sectors to the inspection of Road No. 16 and detailed budget for construction for send to the government as it contemplates buying out rights in the project from the Duangdy Bridge-Road Construction Company.
We are offering the highest and best coverage for cars & motorbikes in Laos !
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“We have already received notice from the government and are waiting for agreement from the taskforce”, Public Works and Transport Department of Champassak province director Mr Soukkaseum Pakdimanivong told Vientiane Times yesterday.
“We expect to start the inspection and negotiation with the company next week. The operation of inspection and negotiation is expected to finish soon after and is expected to be presented to the government before the end of this year,” he said.
“In recent years, many people have complained about the toll fees being so expensive,” Mr Soukkaseum said. Motorists began being charged toll fees on August 17, 2016, with the toll payable varying depending on the type of vehicle they are driving, according to officials.
Based on the fee schedule, cars drivers are required to pay 20,000kip, and mini-bus operators 25,000-30,000.
Meanwhile, 35-seat buses are charged 40,000 kip and heavy trucks or trailers 80,000 kip per one way on this route from the Lao-Japan Bridge to Vangtao-Chongmek International Border Checkpoint.
Southern road users are complaining about the imposition of tolls at two points along the road in Champassak province which runs over a distance of 42 kilometres from the Lao-Japan Mekong Bridge to Vangtao-Chongmek International Border Checkpoint between Laos and Thailand.
Just after the Lao-Japan Mekong Bridge, there is a toll booth while the second is located near the Lao-Thai border.


text:
Finding a bus ticket from Madrid to Seville is not so simple because many bus companies do not offer direct trips to every destination. Fortunately, Kombo has developed a search engine that can combine routes of different buses from different bus operators to generate a map to a specific destination. The good news for you is that you will be able to find cheap bus tickets between Madrid and Seville.
For this trip, bus stops are mainly in Nice. There is only one city in which bus stops are possible. In the best-case scenarios,bus transfers will be at Nice, for a 50h35min trip for a minimum budget of 102,44USD.
To go from Madrid to Seville, the bus is the best choice if you want a cheaper fare, with an average price of %averagePrice% euros. This coach trip on 393 km will allow you to be quiet at least during 50h35min, which is the ideal time to have a good nap. Compared to the train, the bus is often longer but the free WiFi connection will make the time much shorter, especially with its unbeatable price! However, Blablacar's carpooling is often comparable in price and duration to the bus trip. But once again, free WiFi and the comfort of a modern coach will make you prefer the bus.
To pay for your bus ticket to Seville cheaper, we recommend booking directly on Kombo. First of all, here, you are guaranteed to have a seat because many buses can attain their fullest capacity on some roads. Also, you can find the cheapest bus tickets and travel at a lower fare, as we compare ticket prices from several bus and coach operating companies. Finally, you can sometimes take advantage of coupon codes available, either for National Express, Ouibus, Flixbus, Eurolines or Alsa. So our advice to you is to book earlier, it's always cheaper!
Once you have your bus ticket, no need to print it. However, remember to fully charge your phone, as you will need to show the ticket on the screen of your smartphone.
From Madrid, you will leave from the following bus stations:
You will arrive at this bus station To Seville:

domain: geography