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- Open Access
Novel autoantigens immunogenic in COPD patients
Respiratory Research volume 10, Article number: 20 (2009)
Chronic obstructive pulmonary disease (COPD) is a respiratory inflammatory condition with autoimmune features including IgG autoantibodies. In this study we analyze the complexity of the autoantibody response and reveal the nature of the antigens that are recognized by autoantibodies in COPD patients.
An array of 1827 gridded immunogenic peptide clones was established and screened with 17 sera of COPD patients and 60 healthy controls. Protein arrays were evaluated both by visual inspection and a recently developed computer aided image analysis technique. By this computer aided image analysis technique we computed the intensity values for each peptide clone and each serum and calculated the area under the receiver operator characteristics curve (AUC) for each clone and the separation COPD sera versus control sera.
By visual evaluation we detected 381 peptide clones that reacted with autoantibodies of COPD patients including 17 clones that reacted with more than 60% of the COPD sera and seven clones that reacted with more than 90% of the COPD sera. The comparison of COPD sera and controls by the automated image analysis system identified 212 peptide clones with informative AUC values. By in silico sequence analysis we found an enrichment of sequence motives previously associated with immunogenicity.
The identification of a rather complex humoral immune response in COPD patients supports the idea of COPD as a disease with strong autoimmune features. The identification of novel immunogenic antigens is a first step towards a better understanding of the autoimmune component of COPD.
Chronic obstructive pulmonary disease (COPD) is a common pulmonary affection, which is characterized by a range of pathophysiological changes including airflow limitation based on an obstructive bronchiolitis and persistent inflammation with neutrophils, macrophages, B and T lymphocytes and dendritic cells, a mucociliary dysfunction, apoptosis, and on structural changes in the airways causing emphysema, and by extrapulmonary systemic effects [1–3]. The overall global prevalence of COPD in adults that are 40 years or older is approximately 10% . While COPD is currently the fourth leading cause of death worldwide it is expected to be the third leading cause of death in 2020 . Besides, COPD is a major factor for disease-related loss of quality of life, health expenditure and loss of productivity.
Various host and environmental risk factors are supposed to contribute to the development of COPD. Host factors include airway hyperresponsiveness and aberrant lung growth. Several candidate genes are found to contribute to the individual risk. Environmental risk factors include smoking as the first cause followed by air pollution and occupational dust or chemicals .
COPD shares many clinical and pathophysiological features with autoimmune diseases . There is strong evidence for an active adaptive T-cell response in COPD patients . Antielastin antibody and T-helper type 1 responses characterize emphysema as an autoimmune disease . The most recent evidence for a prevalence of IgG autoantibodies in COPD patients further supports the idea of a strong autoimmune component in COPD . However, there is rather limited information on the nature of antigens reacting with autoantibodies in COPD patients. In this study we identified a large number of different antigens immunogenic in COPD patients and determined how many antigens reacted with each COPD serum. Likewise, we determined how many COPD sera reacted with each antigen. Additionally, we compared the reactivity of each antigen between COPD sera and control sera of healthy individuals. The identification of novel immunogenic antigens that allow differentiation of COPD patients from controls is a first step towards the development of new diagnostics and therapies as recently suggested .
Blood samples were obtained from the Departments of Pneumology and Hemostaseology of the Saarland University with patients' informed consent. Serum was isolated from the blood samples and stored as aliquots at -70°C. The patient sera stem from 17 patients with COPD. Spirometrical data and data on smoking behavior are summarized in Table 1. Control sera were obtained from 60 healthy blood donors. None of the included blood donors suffered from pre-existing diseases according to their medical records and as determined by medical examination prior to blood drawing. Information on gender and age of all blood donors is given in Table 2.
Protein macroarray screening
We assembled 1827 different immunogenic clones from high-density protein macroarrays consisting of 38,016 E. coli expressed proteins from the hex1 library  by carrying out a pre-screening with sera of patients with different human diseases. These 1827 E. coli expressed proteins were screened in duplicates with 17 COPD sera and 60 normal control sera. In brief, macroarrays were washed twice with TBSTT (TBS, 0.05% Tween 20, 0.5% Triton X-100) and 4 times with TBS. After blocking with 3% non-fat dry milk powder in TBST (TBS, 0.05% Tween 20), macroarrays were incubated over night with sera 1:1000 diluted in blocking solution (3% non-fat dry milk powder in TBST). After the incubation, sera were stored for the second incubation round. Three washing steps with TBST were followed by incubation with stripping solution at 70°C. Macroarrays were washed twice with TBST and 4 times with TBS. Incubation with blocking solution was followed by a second round of serum incubation over night. Macroarrays were washed three times with TBST, and incubated with secondary antibody (rabbit anti-human IgG, IgA, IgM-Cy5 (H+L)) 1:1000 diluted in blocking solution. Macroarrays were washed four times with TBST, twice with TBS and scanned by the GE Healthcare Typhoon 9410 scanner. The evaluation of the scanned protein arrays was carried out by the image analyzing software tool AIDA version 4.15 and by a newly developed computer-aided analysis procedure.
Computational analysis of seroreactivity patterns
Since manual inspection offers only a subjective and binary analysis of reacting clones, we developed an automated image analysis procedure. After hybridizing the arrays with the different sera, our approach computes the intensity value for each clone on the arrays. Since all clones were spotted in duplicates, the mean value of the two replicates was assigned to each clone. The evaluated antibody profiles were normalized using quantile normalization to minimize between-array-effects. To access the "value" of an antigen with respect to its ability to separate COPD sera from control sera, we calculated the area under the Receiver Operator Characteristics curve (AUC) for each antigen A as follows: the normalized intensities of all control and COPD sera were used as threshold values. For all thresholds t, we considered COPD sera with intensity value above t as true positives (TP), COPD sera with intensity value below t as false negatives (FN), control sera with intensity value below t as true negatives (TN), and control sera with intensity value above t as false positives (FP). Likewise for all thresholds, specificity (TN/(TN+FP)) and sensitivity (TP/(TP+FN)) were computed. Please note that in some cases the classification has to be inverted. In these cases, diseased sera with intensity value below t are considered as 'true positives' (TP). The Receiver Operator Characteristics (ROC) curve shows the specificity as function of one minus the sensitivity. AUC values can range from 0 to 1. An AUC of 0.5 for a spot means that the distribution of intensity values of COPD sera and control sera can not be distinguished. The more the AUC value of an antigen differs from 0.5, the better this antigen is suited to separate between the two serum groups COPD and control. AUCs of 1 or 0 correspond to a perfect separation of spots generated by COPD and control sera. Antigens with AUC values > 0.5 show higher intensity values in COPD sera than in control sera. Antigens with AUC values < 0.5 show higher intensity values in control sera than in COPD sera. A graphical representation of the AUC value computation is provided in Figure 1.
Visual analysis of protein macroarrays
Out of a fetal brain cDNA expression library encompassing more than 38,000 different peptide clones, we compiled a set of 1827 immunogenic clones by screening serum pools of various human diseases. To identify antigens reactive with COPD sera, these peptide clones were screened with 17 sera of patients with COPD and a control group of 60 sera of healthy blood donors. An example of a protein macroarray analyzed with serum is shown in Figure 2. The reactivity of each peptide clone was analyzed by visual evaluation utilizing the image analyzing software AIDA. Each COPD serum detected on average 63 peptide clones. The six most reactive sera identified more than 70 peptide clones per serum and the three least reactive sera identified less than 40 peptide clones per serum. In total, all 17 sera together detected 381 different peptide clones that reacted with autoantibodies of COPD patients.
Next, we asked how frequent does any of the peptide clones react with sera of COPD patients. We detected 17 clones that reacted with more than 60% of all tested COPD sera and seven clones that reacted with more than 90% of all tested COPD sera.
Computational comparison between COPD sera and controls
Autoantibodies are not only found in diseased persons but are also common in healthy individuals. Therefore we analyzed the seroreactivity of antigens not only for COPD patients, but also for healthy blood donors as controls. To perform a low biased evaluation of the arrayed antigens, we utilized our newly developed computer-aided image analysis procedure. This automated evaluation approach allows to compare the seroreactivity of COPD and controls for each antigen. We computed the area under the Receiver Operator Characteristics curve (AUC) by comparing seroreactivity (intensity values) of COPD and control sera for each clone. The overall distribution of AUC values for all 1827 clones is shown in Figure 3. In the following we only examined clones with AUC values < 0.3 or > 0.7 because these clones are best suited to separate COPD from control sera. We found 212 peptide clones, including 67 clones that represent in frame sequences and 145 peptide clones that represent out of frame sequences. The 67 in frame clones represent 58 different genes. Comparison of the autoantibody profiles between male and female controls did not show a statistically significant influence of gender. Likewise, we did not find a significant influence of the age on the autoantibody profiles of normal controls (data not shown).
The best clone (AUC = 0.10) showed sequence homology to FAM36A but represents an out of frame sequence. The spot intensities of clone FAM36A for all sera and the distribution (frequency) of seroreactivity signals according to the spot intensities are shown in Figure 4. The best in frame clone (AUC = 0.87) showed sequence homology to MCM3 that has been identified as immunogenic antigen in colon and prostate cancer. The above mentioned clone FAM36A showed higher immunogenicity in control sera than in COPD sera. Clone MCM3, the best in frame clone, showed higher immunogenicity in COPD sera than in control sera (see Figure 5). In total, 40 of the 67 in frame clones showed higher immunogenicity in COPD sera than in control sera, whereas only 27 of the 67 in frame clones showed higher immunogenicity in control sera than in COPD sera. In addition, 17 clones showed homology to proteins that were identified as immunogenic antigens in various human cancers http://ludwig-sun5.unil.ch/CancerImmunomeDB/. These proteins included NME2, CDC42BPB, RPS2, PTBP1, SON, MCM3, CD320, VIM, CENPB, PDE4DIP, CCNL2, HMG-14, HSPD1, MAZ, RPL6, STUB1, and MBTPS1. Antigens YBX1, HMG-14, and CENPB which showed also informative AUC values are involved in the autoimmune disease systemic sclerosis. CENPB was additionally associated with the autoimmune diseases lupus erythematosus and rheumatoid arthritis [12–15]. Clones with homology to TRAF4 and NME2 have previously been associated with non-cancer lung diseases. More information on all 67 clones is summarized in Additional file 1.
In silico analysis of the in frame peptide clones
Sequence motives like coiled coil, ELR, RGD, and granzyme B cleavage sites can be characteristic for autoantigens [16–18]. We analyzed the 58 different genes with the statistical gene analysis tool "GeneTrail" . Our analysis revealed that 20.7% of the 58 sequences are containing coiled coil motives, whereas only 11.3% of all human gene sequences show such motives. We found approximately 10% more sequences with ELR motives in our test set, i.e. the 58 genes, as compared to the training set. Predicted granzyme B cleavage sites were found in 43.1% of the sequences in our test set and in 40.4% of the sequences in the reference set. In contrast, RGD motives were found in only 5.2% of the sequences in our test set but in 7.5% of the sequences in the reference set.
Out of the 58 genes, eight genes namely RPL37, RPL35, RPS27A, RPL23A, RPL6, RPS2, RPS6, and LOC388720are involved in the KEGG (Kyoto Encyclopaedia of Genes and Genomes) ribosome pathway. RPS6 is also involved in the insulin signalling and the mTOR signalling pathway. MCM3 and VIM are involved in the pathways cell cycle and cell communication, respectively. GTF2B, also known as TFIIB, is a member of the pathway basal transcription factors. HSPD1 is involved in the two pathways Prion disease and Type I diabetes mellitus.
The concept of COPD as an autoimmune disease is supported by the recent findings of frequent IgG autoreactive antibodies in COPD patients [7–10]. In our study, we identified 381 antigens that are immunogenic in COPD patients by screening protein macroarrays with patients' sera followed by a visual evaluation. We identified seven clones that were reactive in more than 90% of all COPD sera. To overcome a bias possibly caused by visual evaluation of the protein macroarrays, we additionally evaluated the macroarrays with a computer aided image analysis procedure that ensures a standardized evaluation of the arrays. Here, we identified 212 peptide clones with informative AUC values < 0.3 and > 0.7 by comparing seroreactivities of COPD patients and healthy controls. Clones with informative AUC values offer themselves as future biomakers for COPD. The identification of biomarkers is however not the focus of our study. Biomarker evaluation requires a study design that tests antigens with informative AUC values for their reactivity against a large number of patients' sera and control sera in a prospective manner. The identified peptide clones provide the basis for such a prospective study. The clones with AUC < 0.3 and > 0.7 included 67 in frame clones, representing 58 different genes and 145 out of frame clones that are termed mimotopes. Mimotopes are defined as peptides capable of binding to the antibody but unrelated in sequence to the natural protein that the antibody recognizes . Since some of the mimotopes yielded rather informative AUC values as for example clone FAM36A, it will be worthwhile to reveal the nature of the natural protein that react in vivo with autoantibodies of COPD patients.
As indicated above a larger number of clones identified in this study were previously associated with an immune response in cancer or with autoimmune diseases. In addition, the two genes TRAF4 and NME2 have been associated with non-cancer lung diseases. TRAF4 deficiency leads to tracheal malformation resulting in airflow limitations in TRAF4-deficient mice . NME2 negatively regulates Rho activity through interactions with other proteins involved in the Rho pathway . In embryonic mouse lungs, the inhibition of the Rho pathway leads in vitro to reduced lung bud formation after 48 hours . Since none of the clones identified in our study has previously been associated with the development or progression of COPD, the newly identified antigens may give leads to as of yet not analyzed cellular processes underlying COPD. Several of the identified antigens are currently discussed as biomarkers including HSP1, MAZ, and RPS2 that are up-regulated in colorectal cancer, acute myeloid leukaemia, and astrocytoma, respectively [24–26]. In addition, future biomarkers may be identified among the antigens NME2, CDC42BPB, RPS2, PTBP1, SON, MCM3, CD320, VIM, CENPB, PDE4DIP, CCNL2, HMG-14, HSPD1, MAZ, RPL6, STUB1, and MBTPS1 all of which have been associated with different human cancers. However, none of the identified antigens has been introduced into clinical practice.
It remains to elucidate what mechanisms contribute to the immunogenicity of each antigen in COPD patients. One hypothesis is that the humoral immune response against disease associated antigens results from overexpression. Although there is some evidence for an association of overexpression and immunogenicity of antigens [27, 28], conclusive experimental proof for a causative role of overexpression has still to be provided. Posttranslational modifications including altered protein folding and processing may also cause a humoral immune response against disease-associated antigens. In addition, mutations are discussed as cause for the humoral immune response against immunogenic antigens . However, we analyzed the reactivity of COPD sera using a cDNA library expressed in E. coli that lack the post-translational modification machinery. In addition, the sequences are highly unlikely to contain specific COPD mutations. Several sequence motives including coiled coil, RGD, ELR and granzyme B cleavage sites have previously been associated with the immunogenicity of antigens [16–18]. We found a slightly elevated percentage of coiled coil motives, ELR motives, and granzyme B cleavage sites in COPD associated antigens. Single analysis of each of these antigens will be required to elucidate the contribution of these motives and other factors to the immunogenicity of the antigens.
Our study provides clear evidence that COPD shows strong autoimmune features. In contrast to previous studies, we not only demonstrated the prevalence of IgG autoantibodies but determined the nature of antigens reacting with autoantibodies in COPD patients. The identification of novel immunogenic antigens that allow differentiation of COPD patients from healthy controls will help to contribute to improved diagnostics and therapies.
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This work was funded by Homburger Forschungsförderungsprogramm (HOMFOR) and by Globus Baumarkt.
The authors declare that they have no competing interests.
PL and EM conceived the study. PL, SH, NL, SR, and VK carried out the macroarray screening. AK and CA did all computational and statistical analysis of the protein macroarrays. PL, AK, HPL, and EM wrote the manuscript. HH, BS, JH, and IS supplied all tested sera and revised this manuscript critically. All authors read and approved the final manuscript.
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Cite this article
Leidinger, P., Keller, A., Heisel, S. et al. Novel autoantigens immunogenic in COPD patients. Respir Res 10, 20 (2009). https://doi.org/10.1186/1465-9921-10-20
- Chronic Obstructive Pulmonary Disease
- Chronic Obstructive Pulmonary Disease Patient
- Control Seron
- Group Chronic Obstructive Pulmonary Disease
- Image Analysis Procedure

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BY Reporters Without Borders
Posted by Bulatlat.com
* 63 journalists and 5 media assistants were killed
* at least 807 journalists were arrested
* 1,308 physically attacked or threatened
* and 1,006 media outlets censored
On 1 January 2006, 126 journalists and 70 cyber-dissidents were in jail around the world
*3 journalists and 15 media assistants were killed
*at least 907 journalists were arrested
* at least 1,146 physically attacked or threatened
*and 622 media outlets censored
The deadliest year for a decade
At last 63 journalists were killed in 2005 while doing their job or for expressing their opinions, the highest annual toll since 1995 (when 64 were killed, 22 of them in Algeria). Five media assistants (fixers, drivers, translators, technicians, security staff and others) were also killed.
For the third year running, Iraq was the world’s most dangerous country for the media, with 24 journalists and 5 media assistants killed. 76 journalists and media assistants have been killed there since the start of fighting in March 2003, more than in the 1955-75 Vietnam War. Terrorist strikes and Iraqi guerrilla attacks were the main cause but the US army killed three of them. Iraqi TV producer Wael al-Bakri, 30, was shot dead by US troops on 28 June. A US Third Infantry Division spokesman admitted the next day in Baghdad that a US unit was involved in his death and said an enquiry had been opened. No result has been announced, nor in the other investigated killings.
In the Philippines too, journalists were killed while trying to inform the public. Their enemies were no longer armed groups but politicians, businessmen and drug-traffickers ready to silence journalists who exposed their crimes. Despite the conviction during the year of the killer of journalist Edgar Damalerio, murdered in 2002 on the island of Mindanao, impunity remained the rule. Journalists in other Asian countries (Afghanistan, Bangladesh, Nepal, Pakistan and Sri Lanka) were also killed because of their work.
Physical attacks on politicians and journalists rocked Lebanon during the year and two leading journalists were killed – Samir Kassir (in June) and Gebran Tueni (December). Kassir was a columnist for the daily An-Nahar and Tueni was the paper’s publisher. May Chidiac, a well-known TV presenter with the station LBC, survived a bomb attack on her car in September but lost a hand and a leg.
Violence against journalists also increased in Africa, with journalists murdered in the Democratic Republic of Congo, Sierra Leone and Somalia and their killers (some of them known) going unpunished. The investigation of the December 2004 murder of Gambian journalist Deyda Hydara, the local correspondent of Agence France-Presse and Reporters Without Borders, made no progress because the authorities did all they could to prevent those responsible from being identified and to ensure they escaped punishment.
In the Americas, two journalists were killed in Mexico for investigating drug smuggling and petrol racketeering.
Several journalists were murdered in Russia and Belarus in shady circumstances and some apparently because of their work. Official investigations there, often biased and politically-influenced, hardly ever produce results.
Physical attacks and threats keep on growing
More than 1,300 physical attacks and threats were recorded by Reporters Without Borders during the year – more than in the previous one.
These occurred almost daily in Bangladesh and Nepal and came from all sides – police, government or opposition party activists and members of armed groups. The attackers are very rarely punished and can thus continue to target journalists undeterred.
Journalist Manjur Morshed was seriously injured when he was badly beaten with a bamboo stick in the southern Bangladeshi town of Baufal in August by a pro-government MP he had accused of corruption. Local journalists demonstrated in protest against the attack.
Election campaigns often bring violence against the media and national votes in Egypt and Azerbaijan saw dozens of physical attacks on journalists reporting on demonstrations and the actual voting.
About 50 journalists were beaten up by police, soldiers or henchmen of local politicians in Nigeria and Peru and accused of not minding their own business. Such violence was worse in the provinces and the journalists were mostly punched or hit with sticks.
Other people attack journalists too and the Peruvian ambassador to Spain, during a trip home to Lima in April, physically attacked a radio journalist who wanted to interview him. The right arm of the reporter, Bettina Mendoza, of the station CPN, was injured. The diplomat later apologized.
Prisons still full of journalists
JOURNALISTS IN JAIL
The same countries are still the world’s biggest prisons for journalists, whose detention there gets ever longer. On 1 January 2006, 126 journalists and 3 media assistants were being held in 23 countries (for the complete list, see www.rsf.org).
In China, journalist and art critic Yu Dongyue has been in prison since the Tiananmen Square massacre in 1989, serving an 18-year sentence for “counter-revolutionary propaganda.” He has gone mad as a result of torture.
Cuba is still the world’s second-biggest prison for journalists and 20 of the 27 journalists arrested in the spring 2003 crackdown are serving sentences of between 14 and 27 years. Four others were jailed in summer 2005 and two of them have still to be tried.
In Burma, the country’s best-known journalist/democrat, Win Tin, entered his 17th year in prison. The ruling generals stubbornly refused to release the 75-year-old former editor of the newspaper Hanthawathi.
Libyan writer Abdullah Ali al-Sanussi al-Darrat is the journalist who has been in prison the longest of anyone He was arrested in 1973, very little is known about him and Libyan officials have never answered repeated requests for information by Reporters Without Borders. It is not known whether he is still alive.
The privately-owned press was abolished in Eritrea in autumn 2001 and its former editors and publishers are still in prison. A hunger strike by them in 2002 had no effect. Their place of detention remains unknown and their families are still not allowed to visit them.
The only figure that has fallen in the past year is the number of journalists arrested (807 compared with 907 in 2004). But this is not good enough, because every day an average of two journalists are arrested somewhere in the world just for trying to do their job.
Cases of censorship up by more than half
At least 1,006 cases of censorship were recording in 2005 (622 the previous year). The big rise was mostly due to the much worse situation in Nepal, where more than half (567) of all cases worldwide were recorded. Since the state of emergency declared by King Gyanendra on 1 February, the media has receiving a battering which is getting harsher. This has included a ban on FM radio stations broadcasting news, blocking of websites, seizure of equipment and politically-inspired distribution of government advertising.
In China, the “broadcasting Great Wall” had new victims, with Voice of Tibet, the BBC, Sound of Hope and Radio Free Asia among the radio stations jammed by the regime with equipment from the French firm Thalès. Media and website editors and publishers get an almost daily list from the government’s propaganda department of topics to avoid.
Censorship continues to rule in Belarus, Kazakhstan and most of Central Asia and newspapers there are still shut down just for criticising the government. Printers and distributors are often used to exert pressure on independent or opposition publications.
The Internet under surveillance
CYBER-DISSIDENTS IN PRISON
The Internet is still tightly controlled by some repressive governments and Reporters Without Borders has drawn up a list of 15 “enemies of the Internet” (Belarus, Burma, China, Cuba, Iran, Libya, the Maldives, Nepal, North Korea, Saudi Arabia, Syria, Tunisia, Turkmenistan, Uzbekistan, Vietnam).
These are the harshest towards online freedom of expression and censor independent news websites and opposition publications, spy on Internet traffic to silence dissident voices and harass, threaten and sometimes throw in prison Internet users and bloggers who deviate from the government line.
In Tunisia, for example, the family of President Zine el-Abidine Ben Ali controls national access to the Internet and he has built up very effective censorship, with the websites of all opposition publications and many news sites blocked. The regime also dissuades people from using webmail, which is harder to monitor than standard e-mail such as Outlook. The Reporters Without Borders website also cannot be seen inside Tunisia. The authorities imprison Internet users who defy them and pro-democracy lawyer Mohammed Abbou was given a three-and-a-half-year jail sentence in April 2005 for criticizing the president online.
The information ministry in Iran boasts that it blocks access to hundreds of thousands of websites. The ruling ayatollahs target any kind of sexual content and also independent news sites. Iran has the grim distinction of having arrested and jailed the most bloggers – a score of them were thrown in prison between autumn 2004 and summer 2005. Mojtaba Saminejad, a 23-year-old blogger, has been in jail since February 2005. He was given a two-year sentence in June for insulting the country’s Supreme Guide. Bulatlat.com

domain: news


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Singapore is not just a paradise of beautiful views and fun activities but is also a paradise to the Indian Cuisines. There is no fact in the doubt that Indians seek for Indian cuisine wherever they go, and availability of great Indian food is one of the specialities of the Singapore city that is known as Little India. Just a walk around Race Course Road will prepare a list of Indian restaurants to dine in. The food is quite cheap, and yes, it is delicious at the same time. Amidst the bustling atmosphere of the city, you get to ease your hunger at the affordable restaurants offering great Indian food. If you are planning to travel to Singapore, you can find the cheapest air ticket fare from Bangalore to Singapore. You can web check-in to save your time.
Some of the famous Indian Restaurants in Singapore include:
Muthu’s Curry: The restaurants situated on the Race Course Road fire up your taste buds with the delectable and spicy food offered. Since 1969, Muthu’s Curry satisfies the hunger and taste buds of many. The restaurant offers most popular fish head curry that you may get addicted to it. The place has an open kitchen situated in the middle of the restaurant that not only adds to the ambience of the place but also gives an assurance to the customers that their food is on the way. It is also noteworthy that it has also won Makansutra Award for 2 consecutive years.
Tandoori Corner on Boon Tat Street: One of the good Indian food venues in the town, Tanddori Corner on Boon Tat Street offers amazing North Indian food at affordable prices. Its Chicken Tikka has already captured many hearts and is bound to capture more. Not just this, you will also be attracted to the aroma of the chicken curry and the ultimate bread corner where you can catch best butter chicken and butter naan of the town. You can also get some of the complementary foods at the restaurant and jazz up your time.
Samy’s Curry: You do not ask for more when you get affordable and tasty food at the classy restaurant. Situated amidst the lush greenery of Dempsey, Samy’s Curry has been described as the curry oasis served in Singapore. The luxurious location of the restaurant offers amazing views that makes dining more enjoyable. Samy’s Curry is one of the finest curry houses in Singapore which serves dishes with a perfect balance of spices.
Gayatri Restaurant: Gayatri Restaurant is another spot on Race Course Road and offers both vegetarian and non-vegetarian options with various specializations from the North and South India. The food is served in generous portions and celebrates the presence of each customer by making dining time an utterly amazing one. On Mondays and Wednesdays, the restaurant offers special hot Fishhead Curry which you can enjoy in the hot curry pot and notice yourself dragging to its fragrance.
Along with the all the above restaurants, there are many others which offer great food at reasonable prices. Khansama Tandoori restaurant, Casuarina Curry Restaurant, MTR 1924, Zaffron Kitchen, Gajalee, Bismillah Biryani Restaurant and many more are on the list. All the restaurants offer great specialities from North and South India that you can lay back in any one of them and savour a casual meal with your family and friends. If you are travelling from Bangalore, you can find cheap air ticket fare from Bangalore to Singapore that would not burn a hole in your pocket for sure.

domain: food


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handprint kids crafts. for longevity or laminate paper hand prints. Christmas craft to create a reindeer picture frame - What a great parent gift idea to make in. 15 Handprint and Footprint Crafts for the Holidays Heather Sokol One of my favorite parts of the holiday season is the kid crafts& projects tucked away among our Christmas decorations.
There are also some cheeky footprints and fingerprints thrown in for good measure. There is something super special about handprint crafts, especially whilst their little hands and feet are still tiny. and believe you me, the “tiny phase” does not last long! 30+ of The BEST Hand and Footprint Art Ideas! Kids crafts with homemade cards, canvas, art, paintings, keepsakes using hand and foot prints!
Handprints and footprints for Christmas keepsakes Posted on December 14, 2017 | 3 Comments Before having kids, Christmas was that glamorous night full of festivities and gifts, delicious food and lots of booze, and back home for the family gathering. Just a few weeks ago, I made the Christmas tree canvas using the hand prints.
I wanted to create this craft with my nieces and nephew (10 y/o, 8 y/o, 7 y/o) and made it for my brother to give to him at Christmas.
Page 2 | Baby footprints are a keepsake that lasts a lifetime. A lasting reminder of those precious days of little feet and hands. BabySakes offers a wide selection of baby footprint kits and baby handprint kits including baby footprint frames for wall hanging or display.
Baby footprints also make great gifts for family members! More Handprint Poems. Contributed by Leanne Guenther and lots of viewers. Thanks everyone!. Footprint Poem. The pitter patter of little feet. Sharon wrote: " I did this with my middle school kids for their moms for Christmas! (next to last line for the boys is I've grown into a young man)" handprint kids crafts. App to digitally capture kids' hand or foot prints to use for diy art and memory books iPad app for storing baby's handprints and footprints!.
for longevity or laminate paper hand prints. Christmas craft to create a reindeer picture frame - What a great parent gift idea to make in the classroom during December!. But, the hand prints and foot prints I have a really hard time throwing away.
There is something about a tiny handprint that gets me every time. So, because I love to encourage hoarding, here are 60 adorable handprint art ideas for kids! Do you remember being young and painting with your hands? What kid doesn’t love it!. about the project at Handprint and Footprint Art. fun to track a child's growth with a new Christmas. Here are 10 creative footprint Christmas crafts to help get you ready for all the holiday season brings, such as festive decorations!
Oct 8, 2016. I've rounded up some of our favorites that are on our craft to-do list for this year. Check out the 21 Christmas handprint and footprint crafts below. Dec 15, 2016. I originally planned on gathering a handful of ideas but as I was searching I kept finding tons of cute Christmas handprint crafts. Needless to say. Preserve your child's hand or footprint with 15 holiday-themed crafts for kids. season is the kid crafts& projects tucked away among our Christmas decorations.
Kid's hand print/foot print crafts for Christmas and winter! Christmas Crafts. Easy Christmas Handprint Footprint Art Ideas | The WHOot by ora. More information. DIY Christmas Hand Print and Foot Print Art - The Perfect DIY. Holiday Handprint and Footprint Art: Handprint Reindeer Art with Footprint - Sleigh did the foot. Find handprint, footprint, & fingerprint crafts for holidays around the world! Also find handprint art for Spring, Summer, Fall, & Winter.
Christmas Crafts, Easter. Reindeer hand& footprint art. More information. Twelve Days of Christmas Handprints and Footprints. See more. Christmas hand& foot Prints for family gifts. Nov 30, 2017. Unleash their inner artist with these fun ideas for Christmas Handprint and Footprint Crafts. My favorite is the Holiday Handprint Charms; I can't.

domain: artistic


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The increased resistance of hypoxic cells to all forms of cancer therapy presents a major barrier to the successful treatment of most solid tumors. Inhibition of the essential kinase Checkpoint kinase 1 (Chk1) has been described as a promising cancer therapy for tumors with high levels of hypoxia-induced replication stress. However, as inhibition of Chk1 affects normal replication and induces DNA damage, these agents also have the potential to induce genomic instability and contribute to tumo...Expand abstract
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CH-01 is a hypoxia-activated prodrug that sensitizes cells to hypoxia/reoxygenation through inhibition of Chk1 and Aurora A.
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domain: medical


British Energy Minister Brian Wilson was concluded a three-day visit to Algeria last week to discuss the possibility of importing liquefied natural gas (KNG) from the North African producer to the UK in the future. Algeria is the EU’s second largest oil and gas supplier, after Russia.
Wilson met President Abdelaziz Bouteflika and Prime Minister Ali Benflis, while an accompanying commercial mission, including representatives from 20 British companies, held talks with officials at Sonatrach, the Algerian state oil and gas company.
© 2003 Mena Report (www.menareport.com)
© 2000 - 2022 Al Bawaba (www.albawaba.com)


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There are few things cuter than a roly-poly Pug or chubby Dachshund feet. Problems start to form when those few extra pounds morph from adorable love handles to debilitating animal obesity. Animals are not immune to obesity or the health problems that come along with the extra poundage. Obesity is a tough battle, especially when you aren’t able to control your own food intake. The animals below each went on the journey to battle their obesity and come out on the other side; no small feat when you don’t have opposable thumbs.
10. Daisy the Bulldog
Daisy the Bulldog from Middlesborough, England was up to sixty-two pounds when her owner Gillian Turrell decided it was time for Daisy to get back her girlish figure. Turrell noted Daisy had been struggling to get up the stairs with her old vigor and the car harness could not longer fit around her ample figure. When the Middleborough Pet Fit Club challenge came about, it was the perfect opportunity for Turrell to get Daisy back into shape under vet supervision. Turrell made previous attempts to motivate Daisy into diet and exercise, but Daisy’s bulldog craftiness prevented any progress, going so far as to jump into strangers’ cars in an effort to get a ride home from the park. Through the Pet Fit Club, Daisy managed to lose seventeen and a half pounds and gain back her waistline along with increased life expectancy and more energy.
9. Kale Chips the Beagle
At his heaviest, Kale Chips the beagle had reached an unbelievable eighty-five pounds. Since his breed is expected to be in the twenty-eight pound range, Kale Chips qualified as wildly obese. Knowing Kale Chips’ situation needed immediate attention, the Chicago, Illinois shelter workers contacted One Tail at a Time Dog Rescue; the volunteers at the rescue took on the challenge and optimistically gave him the Kale Chips name to mark the start of his weight loss journey. In order to transport Kale Chips to the rescue without damaging his joints, the volunteers used a wagon to get him from shelter to rescue. Teaming up with Honest Kitchen for a healthy diet and getting Kale Chips exercising with an underwater treadmill, One Tail at a Time got Kale Chips on his way to a better, healthier life. As of January 2015 Kale Chips had lost twenty-three pounds, with roughly thirty more pounds to go. Kale Chips has inspired The Team Kale Chips Challenge, motivating people to get into a more active lifestyle. In addition, Kale Chips is ready for adoption! See his adoption page here and his photo updates so far.
8. Fifi the Cat
You’d never know from seeing Fifi’s before picture that she used to be a kitten starving on the streets. Before entering her weight loss program, she was quite a formidable looking woman with a sneaky snack streak. Stealing bird food, conning neighbors into free meals, and gorging herself on her owner’s food were just some of the ways Fifi managed to pack on weight to reach twenty-one pounds. Even though Fifi was agile enough when it came to food, her owners knew they needed to help her before it was too late. They joined the UK Pet Fit Club and after restricting her eating habits with a veterinarian’s help, Fifi was able to lose 22% of her body weight. She is now much more active and playful, though her owners have noted she’s much more sassy as well.
7. Rocco the English Bull Terrier
You’d never know that English Bull Terriers are capable of the “Bully Dance” when looking at Rocco back in 2009. His posture and ample belly were enough to bum you out and were proof positive what being overweight feels like for both pets and humans. After attending the prestigious Royal Canin Weight Management Clinic in Liverpool, England with his owners, Rocco has lost a significant amount of weight and now stands tall (and his collar is finally visible!)
6. Ruby the Jack Russell
Before Ruby was the 2013 Pet Slimming Champion of the year, she was a lone Jack Russell stray on the streets of England without a home. When she initially arrived at the shelter, she was underweight with little other backstory. Her new owners adopted her and her worry about where her next meal was coming from was well in the past. Understandably, Ruby’s new family found her hard to resist and made sure she was well fed to a fault. Before they knew it, Ruby was having difficulty getting around and could no longer jump up onto the sofa unassisted. The weight gain happened slowly and before they knew it, Ruby had reached just over twenty pounds. On her small Jack Russell frame, the extra weight was quite stunning. It was at this time that Ruby joined the Pet Fit Club challenge. Over the course of six months, Ruby successfully lost one-third of her bodyweight through simple diet and exercise. Her owner noted, “…now she’s like a puppy again and loves to run on the beach.” Now Ruby has the good life along with a healthy waist!
5. Skinny the cat
A stray Texas tabby cat managed to beef up on the streets of Dallas without an owner. Surviving on the streets, Skinny had made it up to forty-two pounds before a Dallas shelter scooped him up. Initially Skinny lost seven pounds through a special diet to increase his metabolism and he was ready for a family. While he was up for adoption, the vet treating Skinny realized she had become attached to Skinny and made their connection official. She adopted Skinny and continued to treat him for his weight, bringing him down to an amazing twenty-two pounds, nearly to his goal weight. Because Skinny’s love of food lives on, his new owner, Barton, keeps up his diet and exercise regimen. Skinny is now a twenty-two pound city kitty living in Dallas with a whole family to keep track of. Skinny now tends to Barton, her husband, three children, dog, and additional cat now and continues to live the good life while staying truly Skinny.
4. Stone Head the Cat
Former Turkish fat cat Stone Head had reached his literal tipping point. His owner realized Stone Head was in serious need of professional medical attention and brought him to a veterinarian for treatment. Put on a strict protein based diet and trimming down to one meal per day, Stone Head began to shed the pounds. No longer living off high fat foods and eating three times a day, Stone Head is down eleven pounds in four months, with about six pounds left until he reaches his ideal weight. Although his name, Stone Head, refers to a Turkish expression for a dumb person, he is well on his way to being a bright and healthier cat.
3. Dennis the Dachshund
There is something particularly alarming about seeing an obese dachshund and Dennis the dachshund is no exception. Since the ideal weight for a miniature dachshund is in the seven to twelve pound range, Dennis’ fifty-six pound body weight was quite shocking. When Dennis’ new owner Brooke Burton first saw Dennis at his incredible weight, she wasn’t even sure what breed of dog he was; weight had completely obscured any recognizable traits. Burton took ownership of Dennis at that time, determined to get him healthy and off his previous diet of White Castle burgers and pizza that had led to his debilitating condition. Previous to his diet, Dennis was having trouble walking and even breathing; dachshund’s short legs make any weight gain particularly brutal on their tiny joints, making his obesity life-threatening. Burton quickly put Dennis on a dry food diet devoid of fast food and made sure he had a steady exercise routine. After that, Dennis started dropping the pounds, breathing easier, and the standard dachshund sassiness began to appear. Due to the weight loss, Dennis began to trip over his own skin folds and was experiencing infections as a result of the dragging skin. Three surgeries and two years later, Dennis is now an unrecognizable twelve pounds total!
2. Obie the Dachshund
Not to be outdone, Obie is also a dachshund with an incredible weight loss story. A standard dachshund weighing seventy-seven pounds at his heaviest, this big man could barely walk. His extremely large belly and chest would drag on the ground when he waddled, leading to infections on his skin among his already existing walking and breathing issues. Obie also lived off a fast food human diet and quickly packed on the pounds. His owners relinquished him for a better, healthier life and Obie headed to Oregon for his fresh start. After starting a high protein dog food diet Obie began to slowly lose weight. Due to his extremely large size, Obie had to lose weight strictly from diet before safely beginning an exercise regimen. Months went by and Obie faithfully shed the weight. Forty pounds later, Obie was ready for his skin reduction surgery and nearly at his goal weight. At his last weigh-in, Obie was down to an impressive twenty-nine pounds, which is the sweet spot for standard dachshunds. Obie is now active, healthy, and sassy!
1. Poppy the Rabbit
Turns out that it’s not just cats and dogs that have weight issues; Poppy the rabbit from the United Kingdom had ballooned up to over seven pounds. While this may not seem like a hefty weight even for a rabbit, Poppy was still one third heavier than she should be for her breed. Like any pet, Poppy was susceptible to over-treating, with the main culprit being her love of popcorn. Her owner, Donna Manson, said that she especially liked to provide extra treats during cold winter months. Now that Poppy has committed to a healthy rabbit diet, she has slimmed down to a healthy weight.
Whether it’s a rabbit that loses a handful of pounds or a dachshund that sheds the equivalent of a small child, all these animals could definitely give The Biggest Losers a run for their money. All are equally impressive and took initiative from both owners and animal; sometimes it’s hard to resist those big round animal eyes but it can quickly turn into an obesity problem when left unchecked. Luckily these animals dodged an unfortunate, overweight end and can live healthier, happier lives.

domain: pet


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- A promising biotechnology company secures €5M additional funding to advance its therapeutic platform.
- The focus is on developing treatments for neurodegenerative diseases and AL amyloidosis.
- The investment is a testament to the confidence in the company’s innovative approach and potential impact on health care.
Introduction: A Leap Forward in Biomedical Research
In an exciting development for the biotechnology sector, a pioneering preclinical stage biotechnology company has secured an additional €5M in funding. This investment marks a significant endorsement of the company’s innovative approach to tackling some of the most challenging diseases facing humanity today.
The Investment: Catalyst for Advanced Research
A Diverse and Strong Investor Base
The recent financial boost comes from a combination of long-term investors and new stakeholders, showcasing a broad base of support for the company’s vision and scientific approach. This diverse investment portfolio is crucial for the company’s long-term success and stability.
Enhancing Therapeutic Platform Development
The additional €5M funding is earmarked to accelerate the development of the company’s technology platform. This platform is uniquely positioned to address a wide range of amyloid fibril-related diseases, including various neurodegenerative disorders.
Addressing Neurodegenerative Diseases
Novel Approach to Complex Challenges
Neurodegenerative diseases, such as Alzheimer’s and Parkinson’s, pose significant challenges to the medical community. The company’s innovative approach involves developing molecules that bind to amyloid folds in toxic protein aggregates, a promising strategy that could lead to breakthrough treatments.
Expanding the Horizons of Treatment
With this fresh infusion of capital, the company is poised to make significant advances in its preclinical proof-of-concept for leading therapeutic candidates. These developments could pave the way for new, effective treatments for neurodegenerative diseases.
Battling AL Amyloidosis
A Focus on Systemic Pathologies
Apart from neurodegenerative diseases, the company is also making strides in treating systemic amyloidosis, particularly AL amyloidosis. This condition, which affects vital organs and has limited treatment options, represents a significant unmet medical need.
Preparing for Clinical Development
The funding will also support the company’s transition towards clinical development in AL amyloidosis. This step is crucial for bringing these potential treatments from the laboratory to patients who need them.
The Road Ahead: Series B Funding and Clinical Trials
Anticipating the Next Phase
Looking ahead, the company is actively preparing for its Series B funding round in 2024. This future funding is expected to finance phase 1 clinical trials of its lead compound and develop molecules for other indications.
Establishing a New Headquarters
In March 2024, the company plans to establish its headquarters in Liège, Belgium. This new base will not only facilitate laboratory work but also create a modern working environment for its growing team.
Understanding Amyloid-Related Disorders
The Complexity of Neurodegenerative Disorders
Amyloid-related neurodegenerative disorders are characterized by the accumulation of amyloid aggregates in the central nervous system, leading to progressive neurological decline. Current treatments are limited and often target only one protein, whereas the company’s approach is more comprehensive.
Systemic Amyloidosis: A Rare But Serious Condition
Amyloidosis, including AL amyloidosis, is a group of rare diseases where protein aggregates form deposits in various organs. With thousands of new cases diagnosed annually, the development of effective treatments for these conditions is of paramount importance.
About Amyl Therapeutics
Founded in November 2020, Amyl Therapeutics is at the forefront of developing treatments for amyloid-related neurodegenerative and systemic diseases. With a strong foundation of scientific research and a dedicated team, the company is making significant strides in biotechnology.
Conclusion: A Beacon of Hope in Biotechnology
This investment in a leading biotech company represents more than just financial support; it’s a beacon of hope for patients suffering from neurodegenerative diseases and systemic amyloidosis. With a unique approach to treatment and a strong foundation in scientific research, the company is well-positioned to make a significant impact in the healthcare sector.
[For more details on Amyl Therapeutics and its groundbreaking work, visit their website at www.AmylTx.com.]
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domain: economics


A joyous Neil Arce took to social media to express his gratitude to his now fiancee, Angel Locsin, for making a dream of his a reality when she accepted his marriage proposal.
It was on Saturday, June 29, when the couple shocked the public with news of their engagement after more than a year of relationship.
"Thank you for allowing me to be with you, take care of you and most of all love you for the rest of my life," he wrote on Instagram.
Shortly after making the announcement, Angel, in a series of Instagram Stories, thanked fans for their support and shared that she and Arce have yet decide on a date, a venue, and a wedding planner.
It remains unclear as to how, when, and where Neil had popped the question, although it has been revealed that fellow actress Dimples Romana has had a hand in planning the affair when the former publicly thanked her for getting Angel's ring size for him.
Prior to making things official in February the past year, Angel and Neil have been friends for roughly seven years. In a previous interview, the actress said that, although it took some time before she considered a relationship with him, falling in love with the film producer has been the "best part" of her life.


Don Marrazzo – voice
Charikleia Glavopoulou – voice
Dimitris Chandrakis – violin
Chara Sira – viola
Dimitris Patras – violoncello
Nikos Kyriosoglou – piano
Don Marrazzo possesses extensive experience as a voice teacher and arts management professional in the areas of executive management; artistic administration; programming and casting; young artist program development; and community and educational engagement. Mr. Marrazzo has maintained a voice teaching studio since 2002, and his students have performed with opera companies; orchestras; concert venues, and Broadway and Off-Broadway theaters internationally including the Metropolitan Opera; the Lyric Opera of Chicago; The Dallas Opera; The Glimmerglass Festival; the Santa Fe Opera; Staatsoper Stuttgart; Staatstheater Nürnberg, Opéra de Lyon; Oper Bonn; Festival d’Aix-en-Provence; the Dutch National Opera; Tiroler Festspiele Erl; The Grote Zangers Series at the Muziekgebouw; the Cincinnati Symphony Orchestra, the Concertgebouw Orchestra; the Philadelphia Orchestra; the Muziekgebouw; the American Globe Theatre; and the Richard Rodgers Theatre. They have won awards and honors from the Metropolitan Opera National Council Auditions; the George London Foundation; the Sullivan Awards; The Hnatyshyn Foundation; the Sylva Gelber Music Foundation, the Ferruccio Tagliavini International Competition for Opera Singers; the Alumni Enterprise Awards from The Music Academy of the West; the International Vocal Competition of s’Hertogenbosch (IVC); the Fritz and Lavinia Jensen Foundation Competition; the Schuyler Foundation for Career Bridges; the Anna Sosenko Assist Trust; the Canada Council for the Arts; the VSB Fonds; the Joop VandenEnde Foundation; and Classical Young Masters. They have been accepted into prestigious opera studio and training programs including the Lyric Opera of Chicago’s Ryan Opera Center, Santa Fe Opera’s Apprentice Artist Program, the Equilibrium Young Artists Program, and The Opera Academy at the Royal Danish Opera.
Prior to joining The Musical Horizons Conservatory as Head of Vocal Studies and Professor of Voice, Mr. Marrazzo was Head of the Classical Voice Department and Professor of Voice at the Conservatorium van Amsterdam (CvA). Under his leadership, the curriculum, level of student achievement, and international profile of the CvA’s Classical Voice Department grew exponentially. Before his work at the CvA, Mr. Marrazzo was the Executive Director of Astral Artists, an organization committed to the discovery, development, and promotion of the nation’s most gifted emerging classical musicians. Prior to his tenure at Astral Artists, Mr. Marrazzo was the Director of Casting & Artistic Operations for Glimmerglass Opera in Cooperstown, New York. He revitalized Glimmerglass’ mainstage casting, raised its acclaimed Young American Artists Program to an unprecedented level of achievement, and created and fostered collaborations with a number of renowned organizations, companies, and artists including the New York Festival of Song (NYFOS), The Morgan Library and Museum, the Bavarian State Opera, and baritones Håkan Hagegård and François Le Roux. Mr. Marrazzo first joined Glimmerglass as its Director of Public Relations, serving as chief representative to the local, regional, national, and international media, and liaison to the local community. A strong advocate of arts education, Mr. Marrazzo created numerous educational outreach initiatives during his tenure at Glimmerglass.
Mr. Marrazzo has served as a judge for the Metropolitan Opera National Council Auditions, presented seminars and masterclasses for the Graduate Vocal Arts Program at Bard College Conservatory of Music; the National Association of Teachers of Singing (NATS); Opera Viva! In Verona, Italy; Red River Lyric Opera; Penn State University; and Temple University and has served as a presenter and panelist for singer training forums with OPERA America.
A native of Bucks County, Pennsylvania, Mr. Marrazzo holds degrees in vocal performance from the Curtis Institute of Music and the Sweelinck Conservatorium, as well as an M.M. in Classical Voice Pedagogy and Performance and an M.F.A in Voice Pedagogy for Musical Theatre from Penn State University.
Soprano Charikleia Glavopoulou was born in Drama, Greece. She studied at the New Conservatory of Thessaloniki under Varvara Tsampali and graduated with a First Class Solo Diploma. She has attended masterclasses and lessons with Costas Pashalis, Nikos Zahariou, Eleni Karouso, Gabriella Ravazzi, Gabriele Pisani, Sergio Magli, F.M. Carminatti, Czaba Vegvary, George Hadjinikos, Daphne Evaggelatou, Mirella Freni and Cheryl Studer.
She went on to study at postgraduate level in Genova, Italy, with Gabriella Ravazzi and later in Athens with Varvara Gavakou.
Her Italian debut was in the lead role of Silvia in Mascagni’s Zanetto at the Teatro Mancinelli in Orvieto. In Italy, she gave vocal recitals in many cities and also toured with Gruppo Caronte. She also performed themed recitals with works by Greek composers at Teatro Carlo Felice Auditorium in Genova and at the Fiera Internazionale Di Milano.
In Greece she has collaborated with the Thessaloniki Municipal and State Orchestras, Thessaloniki Concert Hall, Thessaloniki Opera and other cultural institutions interpreting roles in Purcell’s Dido and Aeneas, Mozart’s Requiem, Menotti’s O Pulchritudo, Puccini’s Gianni Schicchi, Humperdinck’s Hansel and Gretel, Verdi’s La Traviata and Rigoletto. She has sung under the direction of distinguished maestros such as Loukas Karytinos, Nikos Athinaios, Dimitris Agrafiotis, Viron Fydetzis, Alkis Baltas and Luciano Di Martino.
Mrs Glavopoulou has performed in many music festivals around Greece as well as in solo and chamber music recitals. She performed Respighi’s Il Tramonto with the Aimilios Riadis Quartet at the Dimitria festival; she has also premiered works by Nicolaou with the Macedonian Saxophone Quartet at the Greek Composers Forum as part of the Dimitria festival. She interpreted the lead role of Margarita in the music-theatre show The story of Margarita…by Faust performing works by Schubert, Gounod, Verdi, Boito, Berlioz at the Centre for Drama Research. In 2013 she appeared at the Rhodes and Milos festivals and recently made a guest appearance at an Opera Gala homage to Verdi at the Tellogleio Cultural Centre.
She has been active as a singing teacher since 2000 and has worked at the New Conservatory of Thessaloniki, Music College, National Conservatory and the Municipal Conservatories of Lamia, Drama and Kavala. Since 2012 she has been teaching at the Summer Academy organized by the Municipal Conservatories Network.
Her students have excelled in competitions and have participated by means of audition in masterclasses organized by the Thessaloniki and Athens Megaron as well as other institutions. They have collaborated as soloists with the Thessaloniki State and Municipal orchestras and have performed at the Thessaloniki Megaron amongst distinguished singers under conductors such as Nikos Athinaios, Carolos Trikolidis, Miltos Logiadis and Andreas Tselikas. They have performed at the Centre for Music, the Municipal Theatres of Mitilini, Corfou, Lefkada, the Vafopoulos Cultural Centre of Thessaloniki and the Veria Megaron. In December 2012 her students performed three lead roles at Leoncavallo’s I Pagliacci at Aneton Municipal Theatre of Thessaloniki.
Mrs Glavopoulou is also a graduate of the Law School of the Aristotle University of Thessaloniki.
Born in Thessaloniki-Greece in 1965.
Founder member of the New Hellenic Quartet, he studied the violin at the Thessaloniki State Conservatory under Kosmas Galileas and at the Vienna Music Academy under G. Pichler. He graduated in 1988.
He has appeared as a soloist with all major Greek orchestras.
From 1996 until 2003, he was konzertmeister of the Thessaloniki State Orchestra.
His discography includes all string quartets by Nikos Skalkottas, Giorgos Sicilianos, Mikis Theodorakis, Filippos Tsalachouris as well as the early string quartets by Carl Nielsen and the main chamber music works for string quartet by O.Respighi .
He has been teaching for 20 years at the Thessaloniki State Conservatory. In 2002 he was appointed as a full time professor for violin at the University “Makedonia” of Thessaloniki.
Chara Sira, born in Athens-Greece, studied at the Hellenic Conservatory under Sofia Pimenides and Stelios Kafandaris and at the Conservatoire National Supérieur de Paris under Jean Sulem and Bruno Pasquier. She was awarded a unanimous First Prize with a special distinction in viola in 1994, and went on to complete her training at the Bordeaux Conservatory under Tasso Adamopoulos.
Member of the New Hellenic Quartet from 2001 to 2007, she has recorded works from Skalkotas, Respighi, Nielsen and Koshkin for BIS and has appeared in several chamber music festivals in Europe, the US and Asia.
As a soloist she has appeared with the Thessaloniki State Symphony Orchestra, the Athens Camerata, the National Radio Orchestra and the “Orchestra of Colours”.
A former principal violist of the National Radio Orchestra and the ‘Orchestra of Colours’ in Athens, she now holds the same position in the State Orchestra of Thessaloniki.
She has been teaching the viola for several years at the National Conservatory and the Macedonia University of Thessaloniki.
She is a member of the “A. Riadis” quartet and the “DissonArt Ensemble”.
Born in Thessaloniki, Greece in 1960. At the age of 6 he attended the State Conservatory of Thessalonica where he studied the cello. In 1980, after he received his cello diploma with honors, he earned the scholarship of the german state DAAD and he continued his studies in the “Hochschüle für Musik und Theater” in Hanover, Germany in the class of prof. F.J.Sellheim. He received the diploma of the soloist class in 1986 with honors. The same year, he continued his postgraduate studies in the Vienna Music Academy with André Navarra.
Dimitris Patras has performed as a soloist with all the greek symphony orchestras, with the Hannover Chamber Orchestra, with the french chamber orchestra “Helios’ and he has made many cello and chamber music recitals in music festivals in Greece, Germany, Austria, France, Denmark, Switzerland and Great Britain. He has performed many works of contemporary greek composers, some of which were written especially for him. He has also recorded his performances for the greek, german, danish and french radio and television.
He has taught in numerous international music seminars in Greece and in southern France. From 1989 to 2003 he was the principal solo cellist of the Thessalonica State Symphony Orchestra. He is the cellist of the chamber ensemble “Trio Salonique”. He is cello professor at the University of Macedonia and teaches cello at the Thessalonica State Conservatory.
Nikos Kyriosoglou was born in Serres, Northertn Greece, where he started the piano of twelve. His efforts were so fruitful that three years later he was accepted as a student of Niko Tasopoulo at the State Conservatory of Thessaloniki and later he earned a bachelor’s degree in music from the University of Macedonia-Department of Music Science and Art under the tutelage of the Russian pianist Tatiana Popandopulo. Following his graduation,in 2002, Nikos Kyriosoglou did postgraduate studies at the University of Music in Freiburg, Germany with renowned Professors Gilead Mishory and Pi-Hsien Chen and at the Lemmens Institute in Belgium with Professor Alan Weiss, his principal mentor. Other pianists who had a great influence in his artistic taste include Lazar Berman, Hans Leygraf, Roberto Szidon. .Kyriosoglou has been awarded first prizes and honors in several internationalcompetitions, such as the Thymis Piano Competition, the Muse International Piano Competition and the EPTA Piano Competition. He is also a very active chamber musician, appearing frequently in the most prestigious concert halls of Greece (AthensMegaron, Stavros Niarchos Foundation Cultural Center, Thessaloniki Concert Hall) and throughout Europe (Cyprus, Germany, France, Switzerland, Portugal, Bulgaria, U.K.),making him one of the most celebrated pianists of his generation in Greece. An avid chamber musician, Nikos Kyriosoglou has partnered with renowned peers including Rainer Moog, Rudolf Koelman, Geza Hosszu Legocky, Adriana Contino, Young-Chang Cho, Denis Bouriakov and Christoph Henkel and has performed on virtually every important concert series in Greece. He continuously presents masterclasses and has appeared as a collaborative pianist in the Porto Carras Music Masterclasses, the Montpellier International Summercourses and the Courchevel International Music Academy am ong others.As a soloist, Nikos Kyriosoglou has concertized extensively, performing with all the major Greek orchestras, successfully exploring a repertory that exceeds 17 major concertos, ranging from Haydn, Mozart, Beethoven, Saint-Saens and Liszt to Gershwin,Cage and other masters of the 20thcentury. He has also participated in numerous summer festivals, including the Aegina International Music Festival, Nafplion International Music Festival, Rhodes Festival, and many others. Kyriosoglou maintains active involvement with works of the 20thand 21stcenturies,performing solo and chamber music concerts in his home country, Cyprus, Germany and France.A recording artist, Kyriosoglou joined musical partner Malwina Sosnowski in Montpellier for a recital that was broadcasted by Radio France and Mezzo in 2008. Two years later, Radio BBC 3 selected his recording sand rebroadcasted it to Radio Polskie, NRK, Sveriges Radio, MR3-Bartók Rádió, Radio Romania.His various interests for the piano repertory range from baroque music and early classical period to the late romantic and contemporary period. His interpretation seeks to serve the composers’ demands with clarity and precision, as well as to bring out passion and commitment by using the piano as an instrument of expression and deepening the audience’s connection to music. Kyriosoglou continually explores the boundaries of the repertory and uses it as a vehicle to experiment with the contemporary and unexplored.
Parallel to his busy schedule of concert engagements, Nikos Kyriosoglou devotes much time to teaching, working alongside young talents to foster the next generation of classical music ambassadors and continues to serve as collaborative pianist at the State Conservatory.


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Requiem Gameplay – First Look January 2010
To Learn More About the Game, Check out our Requiem Page.
Requiem Memento Mori is a 3D Horror MMORPG by Gravity, the same studio behind Ragnarok Online and Rose Online. Requiem offers four races and eight 1st jobs to chose from. The game’s most impressive features are the unique environment and high quality graphics & interface. Control your character via WASD, no click-to-move here. In this video I create a Bartuk Warrior but decide to play my Cruxena Rogue instead. The game has a very fast experience rate, I hit level 5 after killing only five monsters. Each class has a unique skill tree and plenty of varied moves including buffs & combat moves. To learn more about Requiem, check out the official MMOHuts Requiem page, which includes a detailed review, tons of screenshots, and additional videos.
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domain: game


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In this month's elections, Washington state, the land of Starbucks and grunge, elected to legalize same-sex marriage. Washington is also home to Microsoft and Bill Gates (who by the way, gave a total of $600,000 to the Washington fight for same-sex marriage) and a bevy of companies and other executives.
The company is in the middle of contract negotiations with its bargaining with the union that represents its engineers, technicians, and clerical workers, SPEEA. Things are are not going so well. The union just rejected the company's second proposal and a strike-authorization vote is now looming in the distance.
Boeing is also getting some negative press over reports that they plan to refuse equal pension benefits to married same-sex couples. In Boeing's ideal world: when an old dorky gay engineer dies, his husband will have to scrape by on his own just to get by.
Ray Goforth, the executive director of Boeing's union, told The Stranger that Boeing is claiming that "pensions are governed by federal law, which doesn't recognize same-sex marriage, thereby trumping the state law on the matter."
This is why the supreme court needs to rule on Prop 8 already. It'll decide if companies can continue to skate around laws, or if they should just shut up and give fair pay to their loyal employees. Hoping for the latter here obviously.

domain: law


"These nutty experiments in privatization are predestined to fail."
BY JOHN BENDEL
Asbury Park Press
Sell New Jersey's toll roads? Toll road privatization is all the rage in state capitals around here.
Pennsylvania speculates it could net from $3 billion to $10 billion from a Pennsylvania Turnpike lease to a private operator. Delaware is considering a lease of the Delaware Turnpike for as much as $4 billion. Indiana actually did it, recently leasing the Indiana Toll Road — its Turnpike — to an Australian/Spanish consortium for 75 years for $3.8 billion.
Here in New Jersey, Gov. Corzine expects to net up to $10 billion for New Jersey's toll roads. It's part of his plan to reduce property taxes, he says.
Privatization advocates claim toll road sales or leases raise cash for new infrastructure and that private ownership will be more efficient. Private owners will run roads like businesses, they say.
Well, private owners might try, but these nutty experiments in privatization are predestined to fail. The reason is simple: Politics always trumps economics.
A privately owned New Jersey Turnpike or Garden State Parkway will lead first to higher tolls, then to lower maintenance and perhaps public subsidy. Ultimately, the state will be compelled to buy back what it should never have sold in the first place. The cost in the end will be enormous.
The future should be clear to anyone willing to look beyond the numbers on the table today.
First, it will be impossible for any privately run toll road to gain and maintain public support. Proponents of private toll roads acknowledge that operators will raise tolls — something politicians haven't the nerve to do. That's the point, they admit with a grin.
But tolls will always have political consequences, no matter who imposes them. In this age of regular E-ZPass statements, the cost of tolls is very visible to all. No public relations strategy, no brilliant marketing plan, no free coffee, no toll-plaza lottery will ease resentment of higher tolls and the company that exacts them.
As tolls rise, we will see more traffic on alternate roads. Look at the record here: after steep Turnpike toll hikes pushed truck traffic onto alternate roads in the early 1990s, New Jersey towns urged the state to impose truck restrictions. Trenton obliged in 1999.
Those rules were overturned by a federal court last February, but the state is now vetting new truck-restriction regulations designed to pass constitutional muster.
That ongoing effort reflects serious political might. Those same local governments will fight overload on "their" roads — even if the traffic is not primarily big trucks. They will push for lower tolls, or at least for tighter control over increases.
On their side of the equation, toll operators will trim expenses. That's what private businesses do. That's how private owners are expected to generate a profit.
But we're talking about fewer employees and less maintenance. Even if maintenance stays the same qualitatively — a questionable proposition — toll payers will perceive cutbacks in every overflowing trash can, tire-busting pothole and snow-covered traffic lane.
How long will it be before accidents are blamed on cutbacks — real or perceived? The bereaved will demand maintenance standards. Editorial writers and commentators will be right behind them. Toll road operators, no matter what they do, will become public villains.
Of course, if tolls and maintenance standards are imposed by law, the private toll road operator will demand subsidies. Talk about a politically distasteful turn of events.
But even if subsidies are not provided, state government will find itself over time pressed to buy the roads back — at a substantial profit for the owners, of course.
What makes politicians, of all people, believe that privately owned public toll roads will function beyond the reach of politics? Nothing is beyond the reach of government — certainly not highways that people perceive to be public property. No contract, no lease, no deed will change that central, altogether reasonable assumption.
Despite what the governor or the lawyers say now, legal agreements cannot protect private toll road operators from future political interference — not even the most ironclad franchises and absolute guarantees.
When a toll road deal goes bad politically — as it has to — politicians in power then will change the law. And if they can't do that, they will find ways to harass toll road owners to achieve the same ends. You'd be amazed how creative politicians can be when it comes to the exercise of power.
No private toll road operator will be able to blow off the Legislature and/or a determined future governor. In the real political world, it will be very popular for an elected official to move against an unpopular toll road operator.
Could there possibly be any other kind?
John Bendel is a former newspaper reporter who covered transportation issues. He is a former member of the Island Heights Borough Council.
© 2007 Asbury Park Press:


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This is how the idea of this drawing came about. I wanted to make a sort of, movie cover of the two of them as grown adults. On a scale of 1-10...I'd rate this a 5. While the drawing, to me, looks good overall, there are a few things I just couldn't fix. One being the angle of "Lex's" head isn't turned correctly. It doesn't look proportioned right to her body. Another thing I don't like is, for the life of me, I COULD NOT get Ariana Richards' likeness in this drawing!!! I tried so hard to make them look just like the actors but I just couldn't get her to work, so I was finally done fiddling with it and decided to move on.
Other than that, I think it looks pretty cool. Not my best but hey, I am still learning! ;) Anyway...here is my finished drawing. I hope you enjoy!!! :)

domain: hobby


Torpedo Spread and Transphasics
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Cryptic Studios Team
Join Date: Jun 2012
02-26-2013, 08:56 AM
Originally Posted by
If a 'phasic torp does 10k dmg and hits a shield..
40% of that damage bleeds through. So 4000.
That 4k damage.. is it then mitigated by armor kinetic resists or is it applied to hull directly, bypassing kinetic resists?
Any damage that penetrates a shield is still subject to resistance scores. In this example, the 4000 that penetrates the target's shield will be reduced according to their Kinetic Resistance Rating.
And actually... I don't have the figures in front of me at the moment to verify, but I'm fairly certain that T-phasics do 40%
bleedthrough. Non-resilient shield arrays already allow 10% through, resulting in a total of 50%. Resilient shields would let through 45% from a T-phasic.
As for the concern that special Torpedo Modes benefit Quantums disproportionately... there is some merit to that claim. And it is, as another poster pointed out, because amplifying a large number by a set percentage yields a larger benefit than amplifying a smaller number by the same percentage. It's possible that those figures could use another review, but it's also possible that they are fine where they are due to the additional benefits/drawbacks of using different types of torpedoes.
Cryptic - Staff Systems Designer
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A Widow and A Friend by Stella Stella
A Widow and A Friend follows Tina Mason at 61, navigating life after the sudden death of her husband of 36 years. The day of his funeral brings a surprising turn with a knock at her door, offering Tina a different way to grieve and an unexpected friendship.
This story gently explores the journey of loss, love, and finding connection in the most unexpected places. Tina, now facing the world as a widow, learns that the process of healing can take many forms and sometimes, support comes from where we least expect it.
As Tina opens her door to new experiences, she discovers that life still holds moments of joy and opportunities for growth. A Widow and A Friend is a heartfelt look at the complexities of starting over and the strength found in companionship. Through Tina’s story, the book invites readers to see grief and healing in a new light, reminding us of the resilience within and the power of a simple act of kindness.Amazon
Excerpt from A Widow and A Friend © Copyright 2024 Stella Stella
SATURDAY Evening, around 7:30pm
It was another mild day in Oakland, California. The temperature had been averaging seventy-five degrees which was nice weather for May.
Tina was experiencing another failed attempt at getting used to the new sound of quietness in her and Mitchell's home. Finally, tired from mindless pacing around the house, she went into the living room, sat in the recliner, and laid her head back. Potential tears welled up in her eyes, but not fully enough to form and roll down her cheeks. She had probably exhausted whatever tears she had left in her. She was just there, in deep thoughts, alone, sad, and distraught. Her entire world had gone somber.
Tina couldn't help thinking about a simple assessment of her life right now. It was a thought that had become an auto-replay over the past few days. She and Mitchell lived in this bi-level Tudor style house for their entire thirty-six years of marriage. It was a well-built craftsman with three bedrooms, all of which were upstairs on the second level. When they originally bought the house, it had two bathrooms, one full bathroom off the master bedroom, and the second bathroom was more of a powder room downstairs at the bottom of the stairs. When Tina became pregnant, they added a second full bathroom upstairs between the other two bedrooms in Jack-and-Jill style.
Just off the front door was a small foyer area leading straight into the living room. At the back of the living room there was a wall separating it from the large, updated chef's kitchen, where they also added a small den area. The entire house was nice and comfortable yet not extravagant. Tina decorated in warm colors, so it always felt updated and homey.
Over the years they had renovated the house twice. The second update was primarily to add a screened deck which they used regularly to host backyard Barbecue’s.
Tina was sixty-one. She was in good shape with no health issues. She had perfect coffee brown skin, like the color of a latte. Her bright brown eyes and short black and grey peppered afro further complimented her complexion. She had soft features and a nice smile that together made her an attractive mature woman. She had always been a curvy size eight, or ten, depending on the outfit.
Aside from her recent sadness, much of her beauty held up well. She was just an older version of the same attractive woman she had always been.
Tina looked like a woman who was kindhearted, and who had lots of love in her life. It was that love and the fulfillment of having been loved that reflected in her face. When she smiled, the only wrinkles were gentle laugh lines around her eyes. She wondered a bit about how she looked at this moment right now. She guessed not very good, considering all that had happened. She sat there and wondered about the next few days, and then what about after that. What would her life become?
Now, it was just her, and the quiet of the home that was usually filled with sounds of her and Mitchell doing their life. Sounds that can easily be taken for granted. Like the sounds of the television, food cooking, dishes clinging and so on. When she was downstairs, she could always hear Mitchell moving around upstairs. The familiar creeks from movement on the hardwood floors was comforting.
My profession is online marketing and development (10+ years experience), check my latest mobile app called Upcoming or my Chrome extensions for ChatGPT. But my real passion is reading books both fiction and non-fiction. I have several favorite authors like James Redfield or Daniel Keyes. If I read a book I always want to find the best part of it, every book has its unique value.

domain: literature


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Folic Acid: Birth Defects COUNT Questions and Answers
What is folic acid?
- Folic acid is a B vitamin. If a woman gets enough folic acid before and during early pregnancy, it can help prevent neural tube defects (major defects of the baby’s brain or spine). Women need 400 micrograms of folic acid every day. Women can get folic acid by taking a vitamin with 400 micrograms of folic acid in it or eating food that is fortified with folic acid (such as some breakfast cereals and foods made with flour enriched with vitamins).
What are neural tube defects?
- Neural tube defects are serious birth defects of the brain and spine. They develop very early in pregnancy when the neural tube, which becomes the brain and the spine, does not close properly. Folic acid is needed for the neural tube to close properly. Starting folic acid intake after the time in development that the neural tube should have closed (after 6 weeks of pregnancy) will not prevent neural tube defects.
- The two most common neural tube defects are spina bifida (affects the spine) and anencephaly (affects the brain).
Who needs folic acid?
- CDC urges all women capable of becoming pregnant to take 400 micrograms of folic acid every day to help prevent neural tube defects (major birth defects of the baby’s brain or spine).
Is folic acid the same as folate?
- The terms ‘folic acid’ and ‘folate’ are often used interchangeably. However, folate is a general term used to describe vitamin B9 which comes in different forms. These include: folic acid, dihydrofolate (DHF), tetrahydrofolate (THF), 5’ 10’ methylenetetrahydrofolate (5’ 10’ MTHF), and 5’ methyltetrahydrofolate (5-MTHF) .
- Folic acid is the synthetic (man-made) form that is used in vitamin supplements and in fortified foods such as rice, pasta, bread and some breakfast cereals. Folic acid has been shown to be effective in preventing neural tube defects in many scientific studies and in countries around the world [2-6].
- Folate can be found in foods such as leafy green vegetables, citrus fruits, and beans. Women should eat a balanced diet of food rich in natural folate. However, it is very difficult for most women to get the daily recommended amount of folate through food alone .
- The effectiveness of supplements containing some form of folate other than folic acid (such as 5-MTHF, or labeled “Natural Folate”) for preventing neural tube defects has not been studied.
Why is folic acid used in food fortification instead of other folate forms?
- Folate in food is easily broken down by heat and light. Folic acid is the more heat-stable form of vitamin B9 and is, therefore, better suited for food fortification since many fortified products, such as bread, are baked .
- Folic acid has been shown to be effective in preventing neural tube defects in randomized control trials, community intervention programs, and food fortification programs. [2-6]
- Folic acid is easily absorbed in the body and studies have shown that it can increase blood folate concentrations across populations (including those with the MTHFR TT variant-see below for addition information) [9, 10].
What is a blood folate concentration?
- Blood folate concentration is the amount of folate measured in the blood. When a woman gets folic acid through foods or supplements, her blood folate concentration increases. When blood folate concentration is too low, there can be medical issues. Very low blood folate concentrations can cause a form of anemia called megaloblastic anemia. Having enough folate in the blood can help improve a woman’s health and can reduce her risk of having a pregnancy affected by a neural tube defect .
- Once a woman starts taking 400 micrograms of folic acid every day it can take several months to reach a blood folate concentration that is high enough to help prevent neural tube defects.
- The amount of folic acid and/or food folate and the length of time it is consumed before pregnancy are the most important factors in achieving a blood folate concentration that is high enough to help prevent neural tube defects.
My doctor has told me I have a variant in MTHFR. Will folic acid work for me?
- Yes. All women, including those who have the MTHFR TT or CT genotype , can benefit from getting 400 micrograms of folic acid each day, especially before and during early pregnancy.
- MTHFR (methyltetrahydrofolate reductase) is an enzyme that plays a role in how people process folate. A common variant of the MTHFR enzyme (also known as the MTHFR TT or CT genotypes) determines how fast certain people can process folate. Even though women with the MTHFR TT or CT genotype process folate more slowly, they can increase their blood folate concentrations enough to help prevent neural tube defects by taking the recommended daily amount (400 micrograms) of folic acid .
- Research studies have shown that in populations with high levels of the MTHFR TT or CT genotype, getting 400 micrograms of folic acid daily before and during early pregnancy can reduce the risk of neural tube defects by up to 85% [5, 11].
- Many studies have shown that consuming folic acid increases blood folate concentrations. For example a research study showed that after three months of consuming 400 micrograms folic acid, blood folate concentrations increased over 250% among women with the MTFHR TT genotype .
- Crider, K.S., L.B. Bailey, and R.J. Berry, Folic acid food fortification-its history, effect, concerns, and future directions. Nutrients, 2011. 3(3): p. 370-84.
- De Wals, P., et al., Reduction in neural-tube defects after folic acid fortification in Canada. N Engl J Med, 2007. 357(2): p. 135-42.
- De Wals, P., et al., Spina bifida before and after folic acid fortification in Canada. Birth Defects Res A Clin Mol Teratol, 2008. 82(9): p. 622-6.
- Czeizel, A.E. and I. Dudas, Prevention of the first occurrence of neural-tube defects by periconceptional vitamin supplementation. N Engl J Med, 1992. 327(26): p. 1832-5.
- Berry, R.J., et al., Prevention of neural-tube defects with folic acid in China. China-U.S. Collaborative Project for Neural Tube Defect Prevention. N Engl J Med, 1999. 341(20): p. 1485-90.
- Prevention of Neural Tube Defects: Results of the Medical Research Council Vitamin Study., in Lancet. 1991. p. 131-7.
- Tinker, S.C., et al., Usual folic acid intakes: a modelling exercise assessing changes in the amount of folic acid in foods and supplements, National Health and Nutrition Examination Survey, 2003-2008. Public Health Nutr, 2012. 15(7): p. 1216-27.
- Seyoum, E. and J. Selhub, Properties of food folates determined by stability and susceptibility to intestinal pteroylpolyglutamate hydrolase action. J Nutr, 1998. 128(11): p. 1956-60.
- Crider, K.S., et al., MTHFR 677C->T genotype is associated with folate and homocysteine concentrations in a large, population-based, double-blind trial of folic acid supplementation. Am J Clin Nutr, 2011. 93(6): p. 1365-72.
- Shelnutt, K.P., et al., Methylenetetrahydrofolate reductase 677C–>T polymorphism affects DNA methylation in response to controlled folate intake in young women. J Nutr Biochem, 2004. 15(9): p. 554-60.
- Crider, K.S., et al., Population red blood cell folate concentrations for prevention of neural tube defects: bayesian model. BMJ, 2014. 349: p. g4554.


Amos Lee Extends US Tour 2022 & Shares ‘See The Light’ Single
Watch the video for "See The Light," the latest preview of the singer-songwriter's upcoming 'Dreamland' album.
Amos Lee added 15 new tour dates to his upcoming 2022 U.S. Tour. Lee will hit the road in support of Dreamland, a new studio album due out via Dualtone Records on February 11 that includes the just-released single “See The Light.”
The singer-songwriter follows a string of 17 previously announced April concerts in the East Coast and Midwest with an appearance at BottleRock in Napa, California on May 29 and a headlining show at Los Angeles’ The Theatre at Ace Hotel on May 31. Amos Lee then hits San Diego on June 3, Tucson on June 4, Mesa on June 5 and Santa Fe on June 7.
A trip to Texas comes next featuring performances in San Antonio on June 9, Houston on June 10 and Austin on June 11. The tour continues with stops in Indianapolis on June 19 and two nights at the famed Ryman Auditorium in Nashville on June 20 and 21. Amos Lee ends the excursion with shows in Chattanooga, Tennessee on June 23; Charleston, South Carolina on June 24 an Durham, North Carolina on June 25.
Neal Francis will open select dates in June. Tickets for the newly added Amos Lee concerts go on sale this Friday, January 21 at 10 a.m. local time. A Tickets Today presale starts tomorrow (Wednesday, January 19) at 10 a.m. local time.
Dreamland contains 11 new songs. The singer-songwriter previously previewed the Christian “Leggy” Langdon-produced follow-up to 2018’s My New Moon with tracks “Shoulda Known Better,” “Into The Clearing” and “Worry No More.” Amos Lee tackles mental health issues on “See The Light.” Watch the video directed by GOODNICETHANKS and featuring Shaina Cardwell and Emerson Davis below:
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