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Expert reveals surprising snacking tips to fuel weight loss – Express

Weight loss can be a daunting journey for many and some may find that they are not losing as much weight as they should be. Many people find themselves mindlessly snacking because of certain emotions or situations like boredom. However an expert has revealed some snacking tips that people should be mindful of when they are trying to achieve weight loss.

Nutrition expert Dr Michael Mosley told theExpress.co.uk: At the heart of weight gain is the hormone, insulin. One of the main reasons why so many people struggle to lose weight is not because they are idle or greedy but because their muscles have become resistant to insulin.

Insulin is a hormone produced by your pancreas. It controls your blood sugar levels, but it does far more than that. It also controls fat storage.

When you eat a meal, particularly one that is rich in sugary carbs, your insulin levels go up.

Also another reason why many people are not seeing weight loss results as quick as they wish to is because regular snacking builds up your calorie intake.

READ MORE:Top tips to lose weight by improving your digestive system

People often find themselves snacking without thinking because of certain emotions or situations like boredom.

Dr Mosely added: When you eat a bit too much and do too little exercise, fat builds up inside your muscles. This is why we strongly encourage people to also increase their activity levels alongside the diet and move more, as this will enhance the improvement in blood sugar levels.

He explains that there are a number of low calorie foods that can be used to increase your overall food volume.

It is also possible to find low calorie snacks (between 50-100 calories a serving) which means you can supplement your three small meals with a couple of extra snacks if you need something to keep you going throughout the day.

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Here are some low fat snacks that could help you last from meal to meal.

Miso soup

Dr Mosely said: At 21 calories a serving, miso soup is very nutritious, warming, tasty and comforting. It is a great way to fill up between meals. It is also very convenient to pop a sachet into a work bag - as all you need to do is add boiling water.

Chopped vegetable sticks

The nutrition expert explains how vegetable sticks are a great option to snack on.

He says: There are so many varieties to opt for too - so you could vary your snacks to avoid boredom. Try slices of a tricolour of peppers; carrot batons; celery sticks; or florets of cauliflower, and because they are fibrous too, they will make you feel fuller between meals.

Berries

Dr Mosely explains how a serving of 100g of blueberries comes in at around 57 calories but can satisfy a sweet craving.

They are also a superfood and have many health benefits like being high in antioxidants.

Nuts

Dr Mosely said: Nuts are a great source of protein and fibre. However, I would advise avoiding salted or sweetened nuts, which can be moreish. 2 almonds equals 28 calories while 7 walnut halves equal 90 calories.

Staying hydrated is really important when trying to lose weight, it will not only keep you hydrated but can also keep hunger at bay.

Dr Mosely also recommends brushing your teeth as soon as you have had your last meal of the day. He says it will help you keep away from all the snacks and it indicates that it is the end of the day.

When trying to achieve weight loss, many people often do it through a diet.

Dr Micheal Mosely founded the healthy lifestyle plan known as The Fast 800. There are three different lifestyle plans which he recommends trying to achieve weight loss.

The first way is known as The Very Fast 800. This involves eating 800 calories a day for a minimum of two weeks.

However it is important to consult a doctor or dietician before undertaking any major diet as everyones body is different and requires a different amount of calories. It may not be healthy for your body to have a sudden decrease in calorie intake so quickly.

One way is the 5:2 diet. This is known as intermittent fasting. For two days a week, you can eat 800 calories, these are known as fasting days. For the other five, you can eat what you wish, sticking to a healthy balanced diet.

One is the Way of Life. This involves eating a healthy Mediterranean-style diet. This doesnt involve calorie counting, just portion control. Portion control will help reduce your daily calorie intake while still eating the same foods.

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How to live longer – the spice you should add to your shopping list to prevent early death – Express

The key to living longer could be to eat a healthy, balanced diet - including at least five portions of fruit and vegetables every day - as well as regular exercise. But you could boost your life expectancy by regularly eating turmeric, it's been claimed.

Maintaining a healthy lifestyle, including a well-rounded diet is crucial to prolonging your lifespan.

You could also boost your lifespan by doing regular exercise. Its the miracle cure weve all been waiting for, according to the NHS.

Making some small diet or lifestyle changes could help to increase your life expectancy and avoid an early death.

Adding more turmeric to your diet could protect against some types of cancer, experts revealed.

READ MORE: How to live longer - the best drink for boosting your life expectancy

"Several spices have been linked to protecting against cancer, including ginger and black pepper.

"But the strongest evidence so far is for turmeric. Several lab-based studies show that curcumin in turmeric seems to be able to kill cancer cels, particularly in the breast, bowel, stomach and skin, plus it even seems to prevent more from growing.

Eating turmeric could also help to protect against dementia, they added.

Curcumin may prevent plaques forming in the brain, which are one of the hallmarks of Alzheimers disease.

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Taking a different path: Health issues have forced Reagan OGrady to retire as a player, but the former Sudbury Wolves defenceman isnt done with hockey…

Reagan OGradys easy smile and affable manner were fixtures at Sudbury Community Arena for roughly two and a half years.

And though he received some difficult news recently, the former Sudbury Wolves defenceman is pressing on with the same positive outlook that helped define his time in the Nickel City.

A recent graduate from the OHL who had plans to attend university and potential to play professionally, OGrady nonetheless announced his retirement earlier this week, following a diagnosis of transverse myelitis, a rare neurological disorder in which the spinal cord becomes inflamed, causing numbness, pain and other, potentially serious complications.

The toughest thing about this happening is I cant go out on my own terms, OGrady, 21, told The Sudbury Star. Its kind of tough to sit here and say that hockey has been taken from me, because I thought I had some stuff left to prove.

OGrady capped his junior career last spring with the Saginaw Spirit, helping them reach the Western Conference final despite playing two rounds with an injured shoulder. He underwent surgery soon after and was staying in Pittsburgh when his father Brendan, was hired to coach his hometown Lindsay Muskies. OGrady returned home to help out behind the bench, and to work occasionally with the local minor midget squad.

He began to feel run down as early as last June, but didnt sense anything was seriously wrong until early February of this year.

We were on the bus back from Trenton and all of a sudden, my legs and my feet started to go numb, OGrady recalled. Im like, this is strange, like that feeling you get when youre lying on your arm and it goes numb, but I didnt think too much of it.

I went to my usual spin class and the next day, I went to practice and I had been wearing my full gear at the time, to get ready for the upcoming season, and about 25 minutes into practice, I skated up to my dad and I was like hey, I think theres legit something wrong here. He said go to the hospital, see whats going on.

I went in on Tuesday and I was released on Friday afternoon, two MRIs later, a CT scan later and a spinal tap later. It was a lot comprehend, what was going on, and they didnt know what was wrong. They said you have to see a neurologist, but its not going to be until September.

He had returned to Pittsburgh, where he was staying with a local family and training for a return to the ice with the University of Prince Edward Island Panthers, hosts of the 2021 University Cup tournament, but continued to have symptoms.

Then, last Thursday, came the news that will forever change my life, in that theres a lot of things Im going to have to change to live a healthy lifestyle now, OGrady said.

That includes giving up hockey, and contact sports in general. People with transverse myelitis sometimes develop multiple sclerosis, and the risk can be higher if they suffer an injury.

He plans to be physically active, but hell have to carefully monitor his condition, with the help of his doctors, especially for the next couple of years.

Like I have said to all the people who have reached out to me, I have always been a competitor, always been a warrior, and I have been through some up and downs and I have overcome some adversity through my career and through my life in general, OGrady said. This is a bump in the road, but at the end of the day, Im going to land on my feet. The NHL was obviously my dream job and my goal, but at the end of the day, I cant sit here and say I cant reach it, because theres different avenues through hockey that are going to take me down my path now.

Hes still determined to work in the game, whether as a coach, manager, in player development or scouting.

I have just taken some time to process what has gone on and find some positives through all these negatives that have come up and have been a road block for me.

Despite his youth, OGrady can look back on a long list of accomplishments in the sport. A first-round pick in the 2014 OHL Priority Selection, he went on to play 285 regular-season games for Kingston, Sudbury, Mississauga and Saginaw, collecting 23 goals and 49 assists. He won gold at the OHL Cup minor midget showcase and silver at the OHL Gold Cup tournament, before representing Canada in the World Under-17 Hockey Challenge in 2014.

He went on a deep run in 2019 with the Spirit, who pushed the eventual-champion Guelph Storm to seven games before finally bowing out. Despite his injury, he had two goals and two assists in the series.

Those things cant be taken from me, OGrady said. I can sit here and wonder what if with a bunch of different scenarios, but my mentality is Im going to get back on my feet and figure out my next steps and work towards another goal that I have set for myself.

Being a hockey player, the hockey community really rallies around you, and I have found that through all the support I have received (this week) and Im very thankful for everybody I have crossed paths with. For me, its all about giving back and I think the reason a lot of people have reached out to me is because of the type of person that I am, always giving back. I have always been told by mentors and role models, people who have played in the OHL or played professional when I was a little kid, that those things go a long way, and I think that has really been ingrained in me and its something I want to do now, to continue the tradition, continue to give back as much as I can.

Reagan OGrady of the Sudbury Wolves helps out at the clubs summer hockey camp in Sudbury, Ont. on Tuesday August 15, 2017.Gino Donato/Sudbury Star/Postmedia Network

A winner of community service awards in both Sudbury and Saginaw, hes proud of his work with children who are sick or have special needs, and treasures the relationships that were kindled as a result.

He has fond memories of visiting Nicholas Fex, a Sudbury youngster who was born with tracheoesophageal fistula and needed several surgeries as a child and teenager.

It brought me joy when I went to see him in the hospital and gave him that jersey and we sat there and played NHL, OGrady recalled. It really brought me back to what life could be like. I cant play hockey any longer, but Im happy that I have done these things and its not about giving me credit, its just about trying to be a good person. I cant instill that enough in people if youre a good teammate, a good friend, a good kid, life after hockey is going to be set up for you, based on the connections and relationships.

Those connections have only been strengthened in recent days, since OGradys announcement.

I met a lot of great guys in Sudbury and I still chat with them, my billets were awesome and I still go up to see them, and its so awesome to see, even after not being in Sudbury for a couple of years, guys are still reaching out to me today. Its a special feeling. I have heard from parents of guys on my team, some billets from Sudbury, people I went to high school with up there. It gives you a greater appreciation for life.

bleeson@postmedia.com

Twitter: @ben_leeson

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The activity of sulfono–AApeptide helical foldamers that mimic GLP-1 – Science Advances

Abstract

Existing long -helix mimicking necessitates the retention of most natural amino acid residues to maintain their biological activity. Here, we report the exploration of helical sulfono--AApeptides with entire unnatural backbones for their ability to structurally and functionally mimic glucagon-like peptide 1 (GLP-1). Our findings suggest that efficient construction of novel GLP-1 receptor (GLP-1R) agonists could be achieved with nanomolar potencies. In addition, the resulting sulfono--AApeptides were also proved to display remarkable stability against enzymatic degradation compared to GLP-1, augmenting their biological potential. This alternative strategy of -helix mimicking, as a proof of concept, could provide a new paradigm to prepare GLP-1R agonists.

The glucagon-like peptide 1 receptor (GLP-1R) (14) belongs to the class B family of G proteincoupled receptors, and its incretin helical peptide ligand GLP-1 (57) analogs are a promising drug candidate for treating type 2 diabetes and obesity. However, the half-life of GLP-1 is very short owing to rapid degradation by proteases (812). Stabilizing GLP-1 is critical in the development of drugs to treat diabetes. Side-chain cross-linking strategies have been used for conformational and metabolic stabilization of GLP-1 (1315). However, unintended contacts between the cross-links and GLP-1R may occur, and the extent of proteolytic stabilization may be limited. It is conceivable that helical foldamers may provide an alternative strategy to develop proteolytically stable GLP-1R agonists. Gellman et al. (16, 17) reported beautiful work mimicking endogenous GLP-1 using conformationally constrained amino acid residues to replace some native residues. The properly designed /-peptides displayed potent and prolonged activity in vivo. Goudreau et al. recently reported the use of oligourea moieties in GLP-1 sequence to improve the pharmaceutical properties of GLP-1 (18). Very recently, Levine et al. (19) used the O-GlcNAcylation to GLP-1 to improve the stability and in vivo activity. However, to the best of our knowledge, there is no report on mimicking GLP-1 using entire unnatural backbones. Mimicking a long -helix by unnatural peptidomimetics is highly challenging owing to the difference in helicity between -helix and helical foldamers yet appealing because complete unnatural backbone could be more resistant to proteolysis than peptide hybrids.

Sulfono--AApeptides are recently introduced as a new class of helical mimetics to address some enduring challenges in disrupting -helixmediated protein-protein interactions (2027). As proteolytically stable peptidomimetics, sulfono--AApeptides exhibit unusual folding stability by adopting a series of helical structures with well-defined hydrogen bonding patterns (21). Half of the residues are introduced by sulfonyl chlorides in sulfono--AApeptides (Fig. 1A), providing enormous chemical diversity. Furthermore, the single crystal of the homogeneous sulfono--AA foldamers reveals a precise three-dimensional (3D) arrangement of their side functional groups and the helical pitch (5.1 versus 5.4 of -helix) (21), leading to helical mimetics for targeting various -helixinteracting proteins (Fig. 1, B and C) (23, 24). We were intrigued whether this -helixmimicking strategy could be used to mimic GLP-1, a very long helical peptide. Functionally, it was unclear whether native GLP-1 could be mimicked by sulfono--AApeptide-based helical foldamers to form potent GLP-1R agonists. Could the critical residues in native GLP-1 still play an important role in sulfono--AApeptides? Additional questions could arise from the monolithic helix structure of sulfono--AApeptides instead of peptide hybrids that may pose extra challenges in interacting with GLP-1R. Without mimicking the exact structure of GLP-1, would the sulfono--AApeptide be capable of mimicking residues on multiple faces of GLP-1 helix? If successful, it would provide a general strategy for the development of GLP-1R agonists with chemically diverse functional groups based on sulfono--AApeptides. This mode of -helix mimicking would offer a new paradigm for mimicking a myriad of long and complex helical peptides. Here, as a proof of concept, we report the first example of foldameric peptidomimetics with entire unnatural residues for GLP-1 mimicking.

(A) The chemical structure of sulfono--AApeptides. a and b denote the chiral side chain and the sulfonamido side chain from the building block, respectively. (B) The crystal structure of a sulfono--AApeptide; the cartoon structure was drawn by PyMoL. (C) Top view of (B). (D and E) Schematic representation of distribution of side chains from sulfono--AApeptides. (D) Side view. (E) Top view, helical wheel.

Analysis of GLP-1/GLP-1R interaction reveals the critical residues on GLP-1 that are responsible for tight binding to GLP-1R (4, 28). Briefly, GLP-1 engages both its N-terminal domain and C-terminal domain to interact with GLP-1R (Fig. 2A). Of the N-terminal domain, interaction of the polar residues H7, E9, T11, T13, and S17 with the seven-transmembrane domain of the receptor is the most crucial (Fig. 2B). Truncated N-terminal domain GLP-1 peptide derivatives are agonists of GLP-1R at nanomolar concentrations in a cyclic adenosine monophosphate (cAMP) assay (29). Sometimes, such N-terminal truncation results in GLP-1R antagonists like GLP-1(9-36) and exendin (9-39) (30, 31). In contrast, hydrophobic residues F28 and L32 dominate the interaction of C-terminal -helix of GLP-1 with the extracellular domain of GLP-1R. Cryotransmission electron microscopy studies indicate that the entire GLP-1 peptides form a fairly straight -helix (4) instead of the G22-kinked helix (2), suggesting that the kink at G22 may be due to the artifact of crystal packing, which alleviates the challenge to mimic both N- and C-terminal domains of GLP-1 simultaneously. A close view of the critical residues on GLP-1 (Fig. 2, B and C) reveals that H7 and T11 are on the same face (X) of the helix, whereas F28 and L32 are on face Y; E9, T13, and T11 are on face Z (X, Y, and Z are designated arbitrarily).

(A) GLP-1 binds to GLP-1R (Protein Data Bank: 5VAI). GLP-1 (7-36) is shown in blue and GLP-1R is represented in green cartoon. (B) The helical domain of GLP-1 with critical residues showing as sticks. (C) Design of sulfono--AApeptide 3, with side chains mimicking the important residues in B. (The helix was built on the crystal structure shown in Fig. 1. X, Y, and Z were designated to indicate the face of residues on the helix, respectively.)

The preliminary analysis prompted our design of helical sulfono--AApeptides that potentially mimic GLP-1. As shown in Fig. 1 (D and E), chiral side chains and sulfonyl sides are distributed perfectly on four faces of helical scaffold, which could be used to mimic critical residues of a native GLP-1 helical domain that interact with GLP-1R. An intimate comparison suggests that side chains 1a and 3a could mimic residues on the X face of GLP-1, 11b and 13b could potentially reproduce the functionality of residues on the Y face of GLP-1, whereas 2a, 4a, and 6a were speculated to capture the ability of E9, T13, and S17. This strategy led to the synthesis of series of sulfono--AApeptides (Table 1, 3 to 16). For comparison purposes, the native GLP-1 peptides were also synthesized (Table 1 and Fig. 3, 1 and 2). The agonistic activity of these peptides was obtained by measuring the receptor-mediated cAMP production in the Chinese hamster ovary (Chok1) cells overexpressed with the hGLP-1R (14, 32). The N-terminal capped and uncapped sulfono--AApeptides 3 and 4 contain desired side chains shown in Fig. 2C. The potency of sulfono--AApeptide 3 is only two orders of magnitude lower than that of GLP-1 1 (39.79 nM versus 0.11 nM) and ~10-fold lower than that of the capped GLP-1 2 (39.79 nM versus 3.33 nM, respectively).

Our findings demonstrate that the design of full-length unnatural peptidomimetics of GLP-1 is viable. The acetyl capped sulfono--AApeptides displayed more potent agonistic effects than those with an unmodified N terminus. The opposite effect was observed for the regular GLP-1 peptides 1 and 2 (Table 1) where acetylation of the N terminus reduced the agonistic potency of GLP-1 (16, 17). These observations are consistent with different helical scaffolds in GLP-1 and the sulfono--AApeptides.

The functional group on position 6b is not highly critical, as the change of methyl group (3 and 4) to a bulky anisole group only resulted in a fourfold decrease in binding affinity (Table 1 and Fig. 3, 5 and 6). Consistent with previous findings, the C-terminal domain is less important than the N-terminal domain, as replacement of the benzyl group on position 11b with a methyl group (7 and 8) only resulted in a twofold decrease in activity compared with 5 and 6. It is known that H7 is a critical residue for both receptor binding and activation, and replacement of H7 with other aromatic groups, such as Phe, virtually retains the same biological function of GLP-1, implying that aromaticity is critical at the N-terminal end (5). This is similarly observed in sulfono--AApeptides (3 and 4). Substitution of phenyl group for Lys side chain resulted in complete loss of activity (9 and 10). As expected, the side chain on position 4a is highly critical. Replacement of the 2-hydroxylpropyl group (the side chain to mimic T13) with a benzyl group led to completely inactive sequences 11 and 12 (Table 1). It is intriguing that the first side chain preferred is the aromatic group, as the longer sequences (13 to 16) completely abolished the activity to activate cAMP release. Overall, these studies revealed excellent structure-activity relationship for sulfono--AApeptides to mimic GLP-1.

To obtain further structural information and assess any conformational changes resulting from chemical modifications, we investigated the secondary structure of homogeneous sulfono--AApeptides 3 to 16 and compared it with that of regular GLP-1 peptides 1 and 2. Circular dichroism (CD) spectra were recorded between 190 and 270 nm in phosphate-buffered saline (PBS). As anticipated, the regular GLP-1 peptides 1 and 2 adopted a right-handed helical conformation, whereas sulfono--AApeptides 3 to 16 reveal a strong cotton effect with a positive maximum at around 208 nm, which is a characteristic of a well-defined left-handed 414 helix (Fig. 4) (21) similar to previously reported homogeneous sulfono--AApeptides.

A major problem limiting the use of GLP-1 analogs is their instability due to the rapid degradation by proteases. Having found peptides 3 and 5 as the lead candidates based on their in vitro potency, we next examined their enzymatic stability in comparison to the regular GLP-1 peptides. The assays were performed by incubating 0.1 mg/ml of peptides 3 and 5 and the regular peptides (1 and 2) with pronase (0.1 mg/ml) in 100 mM ammonium bicarbonate buffer (pH 7.8) at 37C for 24 hours. High-performance liquid chromatography (HPLC)mass spectrometry was then used to analyze the stability of the examined peptides. Unlike the regular GLP-1 peptides 1 and 2, which degraded completely with no intact peptide remaining, sulfono--AApeptides 3 and 5 showed no detectable degradation (Fig. 5A). These results display notable enhancement in the stability of the sulfono--AApeptides against enzymatic degradation, augmenting their potential in therapeutic application. In addition, peptides 3 and 5 also showed remarkable stability in the presence of serum for 24 hours (Fig. 5B), whereas peptides 1 and 2 had more than 60% degradation under the same condition.

(A) Analytic HPLC traces of 1, 2, 3, and 5 before and after incubation with Pronase (0.1 mg/ml). (B) The serum stability of 1, 2, 3, and 5 was determined in 25% serum (v/v) at 37C for 24 hours. (C and D) Pharmacodynamics of the GLP-1 mimic peptides in mice. A Single dose of peptides was intraperitoneally administered into mice 1 hour before the oral glucose tolerance test (OGTT) (2 g/kg glucose). (C) Blood glucose concentrations were monitored for up to 120 min after oral glucose challenge. (D) Average area under the curve (AUC) calculated from OGTT data. Results show mean SEM of six mice per treatment group; *P < 0.05 versus vehicle; t test.

Next, we examined the blood glucoselowering effect of the lead sulfono--AApeptide 3 in comparison to native GLP-1 (Fig. 5, C and D). The peptides were administered as single doses intraperitoneally to C57BL/6 mice (overnight fasted; n = 6 per group) 60 min before a glucose challenge. Two doses of sulfono--AApeptide 3 (4 and 40 mg/kg) were tested, and their efficacies were compared with native GLP-1 (1 mg/kg) and vehicle control. At both doses, sulfono--AApeptide 3 markedly decreased blood glucose levels at the time points of 30 and 45 min with the dose of 40 mg/kg showing a more pronounced effect, suggesting good pharmacodynamic effect in vivo (Fig. 5C). A dose-related decrease in glucose clearance was observed for 3 at both 4 and 40 mg/kg doses (Fig. 5D), consistent with the abovementioned results of the cell-based assay.

In conclusion, we have developed a series of helical sulfono--AApeptides that can structurally and functionally mimic residues on the multiple faces of the -helical domain of GLP-1. These unnatural helical peptidomimetics display potent GLP-1R agonistic activity in cell-based assay and oral glucose tolerance test (OGTT). To the best of our knowledge, this work represents the first example of foldameric peptidomimetics based on an entire unnatural backbone for GLP-1 mimicking. The excellent proteolytic stability of these helical sulfono--AApeptides augments their biological potential. This alternative strategy of -helix mimicking based on sulfono--AApeptides provides a new paradigm for the preparation of GLP-1R agonists. Exploration of this new strategy for the development of more potent GLP-1R agonists is currently underway.

The resin was swelled in N,N-dimethylformamide (DMF) for 5 min before use, followed by treatment with 20% piperidine/DMF solution (2 ml) for 15 min (2) to remove an Fmoc (9-fluorenyl methoxycarbonyl) protecting group, and washed with DCM (3) and DMF (3) afterward. A premixed solution of the Fmoc protected regular amino acid/sulfono--AApeptide building block (2 eq), HOBt (4 eq), and dissolved inorganic carbon (4 eq) in 2 ml of DMF was added to the resin and shaken for 4 hours to complete the coupling reaction. After washing with DCM and DMF, the resin was treated with 20% piperidine/DMF solution for 15 min (2). Another Fmoc protected regular amino acid/sulfono--AApeptide building block (2 eq) was attached on the resin following the procedure in the first coupling step, and the Fmoc protecting group was removed after the coupling reaction was done. The reaction cycles were repeated until the desired sulfono--AApeptides were synthesized. For the capped sequence, the N terminus was treated with acetic anhydride (1 ml) in pyridine (2 ml) (15 min 2). The final sequence was cleaved using trifluoroacetic acid (TFA)/DCM (3 ml, 1:1, v/v) for 3 hours. The cleavage solution was collected, and the beads were washed with DCM (3 ml 2). The solution was combined and evaporated under air flow to give the crude product, which was analyzed and purified by the Water Alliance HPLC System, at flow rates of 1 and 16 ml/min for analytic and preparative HPLC, respectively. The gradient elution method of 5 to 100% of solvent B [0.1% TFA in acetonitrile (MeCN)] in A (0.1% TFA in H2O) over 50 min was performed. All the sulfono--AApeptides were obtained with a purity >95% after prep-HPLC purification.

CD spectra were measured on an Aviv 215 CD spectrometer using a 1-mm path length quartz cuvette, and compound solutions in PBS buffer were prepared using dry weight of the lyophilized solid followed by dilution to give the desired concentration (100 M) and solvent combination (23, 24). Ten scans were averaged for each sample, three times of independent experiments were conducted, and the spectra were averaged. The final spectra were normalized by subtracting the average blank spectra. Molar ellipticity [] (degcm2dmol1) was calculated using the equation[]=obs/(nlc10)where obs is the measured ellipticity in millidegrees, while n is the number of side groups, l is path length in centimeters (0.1 cm), and c is the concentration of the sulfono--AA peptide in molar units.

Chok1 cells overexpressed with GLP-1R were incubated with increased concentration of tested compounds for 30 min at 37C. The dose response is plotted as the HTRF ratio (EM665/615 nm). Data points are the mean SEM of 3 independent experiments with duplicate measurements for each experiment. Half maximal effective concentration (EC50) values were calculated for each duplicate and the mean values for cAMP EC50 SEM are reported in the table (15).

Lead compounds (3 and 5) and regular GLP-1 peptides (1 and 2) (0.1 mg/ml) were incubated with protease (0.1 mg/ml) in 100 mM ammonium bicarbonate buffer (pH 7.8) at 37C for 24 hours (23, 24). Then, the reaction mixtures were concentrated in a speed vacuum at medium temperature to remove water and ammonium bicarbonate. The resulting residues were redissolved in H2O/MeCN and analyzed on a Waters Alliance HPLC system with a flow rate of 1 ml/min and 5 to 100% linear gradient of solvent B (0.1% TFA in MeCN) in A (0.1% TFA in H2O) over a duration of 50 min. The ultraviolet detector was set to 215 nm.

The serum stabilities of peptides were determined in 25% (v/v) aqueous pooled serum from human male AB plasma (Sigma-Aldrich, Milan, Italy) (33). Peptides were dissolved in H2O/MeCN (70:30 v/v) and then diluted in serum and incubated at 37C for 24 hours. Fifty microliters of solution was added to 50 l of MeCN on ice for 20 min and then was centrifuged at 4C for 15 min. The supernatant was diluted with H2O (0.1% TFA) at a final concentration of 0.1 mg/ml analyzed by reversed-phase HPLC. The amount of intact peptide was estimated by integrating the area under the corresponding elution peak monitored at 215 nm.

All animal care and experimental procedures were approved by the Institutional Animal Care and Use Committee of California Institute for Biomedical Research (Calibr) and strictly followed the NIH guidelines for humane treatment of animals. Female Charles River C57BL/6 mice were fasted overnight and then intraperitoneally administered with 100 l of each peptide in PBS (pH 8.2) containing 1% dimethyl sulfoxide. After 60 min, mice were orally or intraperitoneally administered with 2 g of glucose solution per kilogram of body weight and their tail blood glucose levels were measured before (0 min) and after glucose challenge for 2 to 3 hours.

This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license, which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited.

Acknowledgments: Funding: This work was supported by NSF1351265 and NIH1R01GM112652-01A1. Author contributions: W.S. and J.C. designed research; P.S., Z.Z., Y.S., and Z.A. performed research; P.S., C.L., D.H., T.O., V.T.B.N.-T., W.S., and J.C. analyzed data; and P.S., W.S., and J.C. wrote the paper. Competing interests: The authors declare that they have no competing interests. Data and materials availability: All data needed to evaluate the conclusions in the paper are present in the paper and/or the Supplementary Materials. Additional data related to this paper may be requested from the authors.

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The activity of sulfono--AApeptide helical foldamers that mimic GLP-1 - Science Advances

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Japanese politicians and whalers ignore criticism as whaling industry is revived – Japan Today

Japan has a long history of whaling, purportedly dating back to the 12th century. Historically, whale meat was a dietary staple. The nutritious and protein-rich meat-fed families and comprised school lunches throughout the nation for centuries. Nevertheless, the practice is considered barbaric by many members of the larger community. After announcing the end of the 30-year-old moratorium of its whaling program, government officials are facing complaints from numerous global leaders and activist groups. Unshaken,whalers are excitedto revive the practice they consider a part of their cultural heritage.

The History of Whaling In Japan

Japan's history of whaling dates back to the Jomon period (14,000 300 BCE) when stranded whales were harvested for community consumption. Other early accounts of the practice stem from the spirituality and folklore of the Ainu, the native ethnic group of Japan. Yet, the practice did not begin to reflect the modern industry until the use of harpoons in the 12th century.

By the 16th century, whaling was highly organized with open-boat expeditions beginning in the 1570s. As the industry continued to mature throughout the 17th century, fisheries and organized hunting groups developed netting techniques. Hunting groups would spot whales offshore, quickly dispatch, and harvest their catch immediately upon returning to shore. The entire carcass was harvested for meat as well as for making lamp oils, fertilizers, folding fans, and many other products.

The Meiji period of Japan saw the introduction of the expeditious Norwegian-style of whaling. This industrialized technique relied heavily on power-driven vessels, munitions, and other imported expertise.

Whaler Juro Oka benefited greatly during this period. Considered the "father of modern Japanese whaling," he established the first modern Japanese whaling company in 1899. Under his dominance, the industry grew in size.

Although historians and authors had historically lamented the effect of whaling on whale populations, the industry began to face significant blowback during the 20th century. Confrontations erupted with local Japanese communities adversely affected by runoff and other oceanic pollution. Throughout the 1970s and the 1980s, a whaling moratorium was fiercely debated by the international community. Despite political resistance, the government was eventually forced to concede to the ban in 1988 under the threat of United States sanctions.

Whaling Nationalism and Lifting the Moratorium

Like all nations, Japan has a nationalist streak. Writing in the Japan Times,Shaun O'Dwyer suggestedthat a resurging cultural nostalgia has reignited a Japanese interest in its unique whaling culinary culture. Indeed, certain whaling communities and whalers themselves maintain interest in a practice that many considered anachronistic and unethical.

Politicians like Shintaro Maeda, mayor of the whaling city Shimonoseki, have aggressively campaigned for the resurgence. According to the above-mentioned Japan Times article, Maeda suggested at a public forum that an official declaration of whaling history and culture as Japanese Heritage' be made through the Cultural Affairs Agency, a special body of the Ministry of Education, Culture, Sports, Science and Technology that promotes arts and culture. The initiative implies state subsidies be allocated to reinvigorate the industry.

Maeda is not alone. Shigeto Hase, head of the fisheries ministry, has also championed a resurgence of whaling. Hetold the BBC, "the resumption of commercial whaling has been an ardent wish for whalers across the country." He continued, "the culture and way of life will be passed on to the next generation.

It would appear that the LDP and Prime Minister Shinzo Abe were sensitive to such nostalgia. In December 2018, the Japanese government withdrew from the IWC. Previously limited to scientific research, commercial whaling reconvened in the country in 2019.

Domestic and International Outcry

Unsurprisingly, the decision was met with widespread criticism. Conservation groups and numerous governments were forced to denounce reinvigorating the industry. Australialabeled the decision "regrettable,"while others called on the country to realign with international standards. Sam Annesley, executive director at Greenpeace Japan,saidthe move was "out of step with the international community, let alone the protection needed to safeguard the future of our oceans and these majestic creatures." He also called on the Japanese government to conserve marine ecosystems.

Perhaps such criticisms are easy to support. Prior to 1987, whale meat was widely served in Japanese schools for lunch. Since its removal following the moratorium, the consumption of the meat has dropped precipitously as many now consider it an uncommon delicacy popular with a minority of residents. Reports of mercury contamination makes matters worse.

Observations such as these have inspired a burgeoning sense of domestic activism in Japan. Angered by how the industry distorts the image of their country abroad, opponents like Takayo Yamaguchihave launched online campaigns in defense of marine mammals. Members of Greenpeace, on the other hand, have worked aggressively to blow the whistle on whalers operating under the guise of scientific research.

Activists do this because the Japanese public is sensitively poised when it comes to the legality of the traditional marine stock. As mentioned, interest in whale meat has in general declined. Nevertheless, many residents do not want to appear complicit or be seen as folding to unruly international pressure.

Their unease is justifiable. Actors such as Sea Shepherd and Australian anti-whalers have instigated confrontations with whalers, and perhaps unwittingly, undermined their cause in terms of domestic support. Others still cringe when outlets such as theNew York Times suggestthat whales are highly intelligent and implies that their slaughter is tantamount to murder.

Nevertheless, criticism comes easily. Celebrities likely Ricky Gervais and Joanna Lumley havespoken out. In an open letter, the two, among other personalities, attempted to shame Japanese politicians. Others still called for an "international whaling intervention" to be staged at G20 summit meetings.

However, Japanese officials appear unsympathetic. Riding a wave of nationalism, they are likely uninterested in denying cultural and nationalist initiatives. After all, whale meat helped the nation survive post-WWII poverty, and the moratorium was essentially a foreign intervention. Folding to foreign intervention again would not serve nationalist sentiment.

Nevertheless, if Japan continues with commercial whaling, it will be forced to endure calls of "barbarism" and "anti-environmentalism" from the larger community.

Read more stories from grape Japan.

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SOLIUS Announces Investment from Human Longevity Inc. to Support Mission of Improving Health, Performance, and Longevity. – PRNewswire

SEATTLE, May 13, 2020 /PRNewswire/ --SOLIUS, a developer of innovative light therapy technologies focused on mitigating vitamin D deficiency, today announced investment from Human Longevity, Inc. (HLI) into its Series B financing.

The SOLIUS technology stimulates the production of vitamin D in the skin using a narrow spectrum of ultraviolet B (UVB) light. Vitamin D has a wide range of impact on systemic health, and supports physical, mental and immune function. SOLIUS delivers safe and effective light therapy using a personalized dosing system while filtering out nearly all other ultraviolet light. The SOLIUS technology can produce 10x more vitamin D than the sun, using 100x less ultraviolet energy. This technology is also an effective solution for at risk populations unable to absorb vitamin D orally.

HIL is a pioneer and leader in the delivery of data-driven, predictive precision health intelligence. Wei-Wu He, PhD, Executive Chairman, HLI stated: "We are excited to invest in SOLIUS as its mission is to provide the benefits of the sun without the harmful rays to unlock the healing powers of the human body. Investing in SOLIUS is another example of HLI's expertise in aggregating and leveraging technologies designed to demonstrably increase health, performance and lifespan. I welcome SOLIUS to our emerging ecosystem of longevity and performance-focused companies."

Bob Wise, SOLIUS CEO, said "Humans need sun exposure to stay healthy, and the benefits of the sun cannot be fully replicated with hormone replacement, such as oral vitamin D supplements. We are excited to partner with HLI in developing technologies that prevent disease and improve human health."

ABOUT SOLIUSSOLIUS was founded to advance the understanding of photobiology and the impact that ultraviolet light has on the human body. SOLIUS is dedicated to developing light therapies that stimulate the production of hormones via the skin. The SOLIUS products aim to improve health for people affected by conditions scientifically correlated with a reduction in sun exposure and vitamin D deficiency. For more information, visit http://www.solius.com.

About HLIHuman Longevity, Inc. (HLI) is a genomics-based, health intelligence company empowering proactive healthcare and enabling a life better lived. HLI's business focus includes the Health Nucleus, a genomic-powered, precision medicine center which uses whole-genome sequencing analysis, advanced imaging, and blood analytics, to deliver the most complete picture of individual health.

Contact: [emailprotected]

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Expert Jason Hope on using AI to learn from pandemic – Augusta Free Press

Published Thursday, May. 14, 2020, 8:33 pm

Front Page Business Expert Jason Hope on using AI to learn from pandemic

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Since the initial recognition of COVID-19, and throughout the remarkable trajectory of the global pandemic to date, the scientific community has sought to garner unprecedented insight regarding the connection between Coronavirus, and a myriad of human connections. From the Epidemiologists investigating patterns of infection throughout the world to the Biologists seeking an effective vaccination, the scientific community is brimming with brilliant minds searching for ways to gain an understanding of the pandemic, the human body, modern disease mitigation, and the impacts of COVID-19 on other aspects of the general lifespan. For Jason Hope, along with researchers in the niche field of longevity studies, the Coronavirus pandemic has opened a breadth of new considerations, topics of study, and important connections that could impact the quest for long-term wellness and preservation.

As a widely renowned thought leader and champion within the realm of human longevity research, expert Jason Hope has dedicated his breadth of time, experience, and knowledge to propel technology, public understanding, and research needed to propel the field. With a firm belief in the potential benefits that a broader understanding of human longevity can provide, the entrepreneur and mentor, who previously developed a successful mobile communications company, now focuses on leveraging his skills to drive the field forward. Recently, shed light on the connection between artificial intelligence, human longevity, and the COVID-19 pandemic.

In discussing the impact of COVID-19 within the field of longevity studies, Hope sat down with the Director of Aging Research at Kings College London, Dr. Richard Siow. After his own firsthand experience with battling Coronavirus-like symptoms, Siow spoke at length about the experience, his understanding of the pandemic as it related to human longevity, and what the scientific community can learn from the current Coronavirus pandemic.

In speaking about his experience, Siow shared that he did stop taking the immunosuppressives for the two weeks to try and recover, so Ive also had an increase in my arthritis symptoms. So you can see that there are consequences for my Longevity by having an underlying health condition. According to Hope, it can be surmised that individuals who test positive for COVID-19 may experience a myriad of symptoms, potentially more difficult to deal with in the presence of other already present healthcare conditions. Thus, when utilizing medications or treatments to combat the symptoms of Coronavirus, these individuals may experience a resurgence of symptoms related to their other existing conditions, sparked by medication interaction, or a push-and-pull effect of the human body. In this sense, the presence of COVID-19 in any individual can directly impact overall wellness, the aging of the body, and the prospect of increasing longevity.

With these vastly important conclusions in play, it is important for professionals within the field of anti-aging and human longevity to research ways to mitigate the negative impacts of infectious diseases like COVID-19 in terms of longevity. While Dr. Siows previous studies focused primarily on cardiovascular aging, the current pandemics interference with human longevity has motivated him to pivot his studies. Dr. Siow has stated, my interest now is to align my research background and the longevity consequences of COVID-19 and see how my research might be able to mitigate and prevent some of these long term impacts on health and wellness and also future infections. As a trusted thought provider in the field, Hope touts that this increased focus on maintaining longevity efforts for individuals affected by infectious conditions like COVID-19 will undoubtedly create a much more informed, efficient, and successful blueprint for action, in the event of a future pandemic outbreak.

While the presence of Coronavirus presents immediate risks and dangers to individuals, it also poses long-term concerns and can exacerbate conditions that may remain dangerous long after the virus leaves the individual. While a full recovery may signal the disappearance of immediately related COVID-19 symptoms, it doesnt account for the potentially grim aftermath that the presence of Coronavirus may leave behind. Experts like Jason Hope ponder the notion that COVID-19 could potentially predispose individuals to the future emergence of age-related conditions, including dementia, heart disease, and other serious medical considerations. Thus, increasing overall human resilience may be the key to boost overall wellness, longevity, and health, which could minimize the seriousness of symptoms for future outbreaks.

In seeking scientifically backed answers to these very current considerations, Dr. Siow looks to personalization, technology, and artificial intelligence to customize prevention to meet the needs of every individual. At the Longevity AI Consortium, a Kings College initiative focused on marrying industry and academic personnel to create personalized aging insights, garnering insight from healthy individuals is the first step to creating a roadmap for maintaining wellness. To do this, Dr. Siow looks at specific biomarkers for wellness to create proactive planning to retain health and wellness through positive intervention. Championing the potential impact of this proactive approach, Hope notes that creating a bespoke and effective proactive regimen for individuals to follow could greatly impact their ability to harness an efficient immune system and be best prepared to stave off potential complications throughout another outbreak like the current Coronavirus pandemic.

Bridging the tech-based advancements with the practical consumer-facing application will be the key to generating universal data sets that can then be analyzed, and utilized to create trustworthy statistics, recommendations, and information that can undoubtedly help individuals across the globe. While this sector remains fragmented, philanthropists and investors like Jason Hope believe that through constant advancement, the marriage of AI, technology, science, and medicine, will be able to propel the field of anti-aging and human longevity forward. With broad considerations for the myriad of ways that different facets of human functionality impact longevity on a long-term basis, growth within the field can unlock answers that can help countless individuals to remain healthy well into the geriatric age. Furthermore, in times of a global healthcare crisis, the field of longevity can offer unparalleled insight into how conditions like COVID-19 can impede longevity, exacerbate tertiary conditions, and create long-term negative effects.

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Longevity and Anti-senescence Therapy Market Projected to Experience Major Revenue Boost During the Forecast Period Between 2020-2026 | Covid-19…

ReportsnReports recently added a detailed overview and industry professional survey report on the global Longevity and Anti-senescence Therapy Market. In this report, titled Longevity and Anti-senescence Therapy Market Size, Share and Industry Analysis by Technologies, By Product, By Application, By Distribution Channel, and Regional Forecast 2019-2026.

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The scope of the report encompasses the major types of Longevity and Anti-senescence Therapy Market that have been used, as well as the major applications being developed by industry, academic researchers and their commercialization offices, and government agencies. It analyzes the current market status, examines future market drivers, and presents forecasts of growth over the next five years. Technology developments, including the latest trends, are discussed. Other influential factors such as screening strategies for pharmaceuticals have also been included.

The global Longevity and Anti-senescence Therapy Market is comprehensively profiled in the report, including a detailed study of the markets key drivers and restraints, major market players, and leading segments.

Report Scope:

The scope of this report is broad and covers various therapies currently under trials in the global longevity and anti-senescence therapy market. The market estimation has been performed with consideration for revenue generation in the forecast years 2018-2023 after the expected availability of products in the market by 2023. The global longevity and anti-senescence therapy market has been segmented by the following therapies: Senolytic drug therapy, Gene therapy, Immunotherapy and Other therapies which includes stem cell-based therapies, etc.

Revenue forecasts from 2028 to 2023 are given for each therapy and application, with estimated values derived from the expected revenue generation in the first year of launch.

The report also includes a discussion of the major players performing research or the potential players across each regional longevity and anti-senescence therapy market. Further, it explains the major drivers and regional dynamics of the global longevity and anti-senescence therapy market and current trends within the industry.

The report concludes with a special focus on the vendor landscape and includes detailed profiles of the major vendors and potential entrants in the global longevity and anti-senescence therapy market.

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Report Includes:

71 data tables and 40 additional tables An overview of the global longevity and anti-senescence therapy market Analyses of global market trends, with data from 2017 and 2018, and projections of compound annual growth rates (CAGRs) through 2023 Country specific data and analysis for the United States, Canada, Japan, China, India, U.K., France, Germany, Spain, Australia, Middle East and Africa Detailed description of various anti-senescence therapies, such as senolytic drug therapy, gene therapy, immunotherapy and other stem cell therapies, and their influence in slowing down aging or reverse aging process Coverage of various therapeutic drugs, devices and technologies and information on compounds used for the development of anti-ageing therapeutics A look at the clinical trials and expected launch of anti-senescence products Detailed profiles of the market leading companies and potential entrants in the global longevity and anti-senescence therapy market, including AgeX Therapeutics, CohBar Inc., PowerVision Inc., T.A. Sciences and Unity Biotechnology

Summary:

Global longevity and anti-senescence therapy market deals in the adoption of different therapies and treatment options used to extend human longevity and lifespan. ?Human longevity is typically used to describe the length of an individuals lifetime and is sometimes used as a synonym for ?life expectancy in the demography. ?Anti-senescence is the process by which cells stop dividing irreversibly and enter a stage of permanent growth arrest, eliminating cell death. Anti-senescence therapy is used in the treatment of senescence induced through unrepaired DNA damage or other cellular stresses.

Global longevity and anti-senescence market will witness rapid growth over the forecast period (2018-2023) owing to an increasing emphasis on Stem Cell Research and an increasing demand for cell-based assays in research and development.

An increasing geriatric population across the globe and a rising awareness of antiaging products among generation Y and later generations are the major factors expected to promote the growth of global longevity and anti-senescence market. Factors such as a surging level of disposable income and increasing advancements in anti-senescence technologies are also providing traction to the global longevity and anti-senescence market growth over the forecast period (2018-2023).

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According to the National Institutes of Health (NIH), the total geriatric population across the globe in 2016 was over REDACTED. By 2022, the global geriatric population (65 years and above) is anticipated to reach over REDACTED. An increasing geriatric population across the globe will generate huge growth prospectus to the market.

Senolytics, placenta stem cells and blood transfusions are some of the hot technologies picking up pace in the longevity and anti-anti-senescence market. Companies and start-ups across the globe such as Unity Biotechnology, Human Longevity Inc., Calico Life Sciences, Acorda Therapeutics, etc. are working extensively in this field for the extension of human longevity by focusing on study of genomics, microbiome, bioinformatics and stem cell therapies, etc. These factors are poised to drive market growth over the forecast period.

Global longevity and anti-senescence market is projected to rise at a CAGR of REDACTED during the forecast period of 2018 through 2023. In 2023, total revenues are expected to reach REDACTED, registering REDACTED in growth from REDACTED in 2018.

The report provides analysis based on each market segment including therapies and application. The therapies segment is further sub-segmented into Senolytic drug therapy, Gene therapy, Immunotherapy and Others. Senolytic drug therapy held the largest market revenue share of REDACTED in 2017. By 2023, total revenue from senolytic drug therapy is expected to reach REDACTED. Gene therapy segment is estimated to rise at the highest CAGR of REDACTED till 2023. The fastest growth of the gene therapy segment is due to the Large investments in genomics. For Instance; The National Human Genome Research Institute (U.S.) had a budget grant of REDACTED for REDACTED research projects in 2015, thus increasing funding to REDACTED for approximately REDACTED projects in 2016.

The latest Longevity and Anti-senescence Therapy Market report provides readers with a deeper understanding of potential target consumers to create a lucrative marketing strategy for the 2019-2026 forecast period. For entrepreneurs seeking information about potential customers, it will be particularly helpful. Selective statements provided by leading vendors would allow entrepreneurs to gain a deeper understanding of the local market and prospective customers.

Table of Contents:

Chapter 1 Introduction

Study Background

Study Goals and Objectives

Reasons for Doing This Study

Scope of Report

Methodology and Information Sources

Geographic Breakdown

Market Breakdown

Analysts Credentials

.Continued

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Eight O&M steps to extend the longevity of hydropower plants – ESI Africa

The cost of implementing a robust operations and maintenance (O&M) strategy for hydropower accounts for a relatively small percentage of the value of electricity generated. However, failure to implement adequate and sufficient O&M can result in very high costs due to increased losses of production (direct and indirect) and higher needs for rehabilitation and equipment replacement.

This article first appeared inESI AfricaIssue 2-2020.Read thefulldigimaghereorsubscribe to receive a print copy here.

The development of hydropower continues throughout the world, with some 22GW of hydropower being added in 2018, bringing the worlds hydropower capacity to around 1,290GW. In 2018, the estimated generation from these facilities amounted to 4,200TWh, or some 16% of the worlds electricity production.

A key distinguishing feature of hydropower is its potential longevity. A hydropower facility can operate for 100 years or more, compared with 20-30 years for most other generation technologies. This article outlines the best O&M strategies that can be applied to maintain the longevity of hydropower plants through a step-by-step approach.

Step 1: Diagnose existing O&M arrangements, budgets and owner/operator capabilities

For existing hydropower fleets, assess the condition and performance of theassets and services, including risks related to major equipment and need for replacement and repairs. The intended outcome of the diagnosis is toidentify what aspects of O&M need to be improved, and to establish whether the owner needs external assistance for operation of its assets.

Carrying out the diagnosis is also a good preliminary tool for assessing the status of the existing equipment, prioritising rehabilitation and, if needed, launching related feasibility studies to improve performance and ensure future safe operation. Diagnosis of an existing fleets performance can focus on contractual or standard industry key performance indicators (KPIs).

When financing a new facility to be added to an existing fleet, considerationshould be given to the current fleets O&M performance record. This will help guide the O&M strategy for the new facility, and possibly trigger changes to the O&M strategy for the existing fleet. Where the new project is a stand-alone facility, including those developed by an independent power producer (IPP), the same KPIs can be assessed on past or existing facilities for which the IPP team has or had responsibility.

Step 2: Define the objectives to be achieved through the implementation of the O&M strategy

Meeting the define objectives based on the diagnosis in Step 1 should be seen as a long-term goal that may require multiple iterations, such as changes in the operational management of facilities, short- and medium-term maintenance, and refurbishment, or the upgrading of the facilities. In order to ensure that a companys business plan does not become too focused on only one or two performance areas (such as finance or reliability), multiple goals and objectives are required.

The objectives of the strategy must be defined by indicators to be applied at all levels, including technical, financial, human resource services, and management, among others. Vision and mission statements may be used, if they exist, or formulated, if they do not, as an anchor point for the O&M strategy. Their primary objective is to communicate the companys strategic goals and is often linked to operational performance. Such vision and mission statements only have value if they are used by management as guiding principles for the business.

Step 3: Explore various activities to be undertaken to achieve these objectives

Considerations to be addressed while preparing the list of activities for the O&M strategy should go beyond assessment of asset repairs and refurbishment to examining root causes and long-term and sustainable solutions. The output from this step includes identification of the core activities and measures required in order to achieve the strategic objectives established in Step 2, based on the diagnosis completed in Step 1.

Step 4: Examination of O&M contractual models

Depending on the capabilities identified in Step 1, along with the activities selected in Step 3, explore O&M contractual models to identify which activities will be implemented internally and which will be outsourced. This can be broken down into three models to identify which model works best, namely:

Model one: Owner retains sole responsibility for O&M. Model two: Owner outsources some O&M responsibilities to consultants, contractors, or suppliers. Model three: Owner outsources all O&M responsibility to an independent operator.

Step 5: Training and human resources management

Explore organisation and staffing options (and organograms) according to owner capacity and requirements for external training and human resources. The success of the organisation depends on the quality of its employees (skills, knowledge, and experience) at all levels of the company and how well the human resources are selected, trained, and managed.

The differences between the performance of well-run and poorly performing utility fleets are evident at multiple levels. The greatest responsibility rests at the senior and management levels. Shortcomings should be identified during the diagnosis in Step 1 and through a more detailed operational audit.

Step 6: Financing for the implementation of the O&M strategy

Estimate financial resources required for implementing the selected model, including any external contracting. For the purposes of validating the O&M strategy, the costs are often estimated in USD. However, local or other international currencies may also be used, matching the currency that was adopted for estimating the benefits in Step 2. The costs of hydropower facility O&M vary considerably due to a range of factors including:

Nature of the facilities: complex facilities with multiple units, extensive civil works, and extensive associated infrastructure cost more to operate than simple compact facilities.

Age: older hydropower facilities with manual controls, analogue systems, and outdated equipment cost more to operate than modern, fully automated, remotely operated digitalised plants.

Condition: facilities in poor condition requiring continuous attention and suffering frequent failures cost more to operate than facilities in good condition. Facilities in poor condition are likely to require significant capital investment programmes.

Location: facilities in remote locations, especially where accommodation, utilities, and other facilities need to be provided for O&M staff, cost more than hydropower facilities in urban locations.

Country: since staff costs form a significant portion of OPEX, the labour costs and available skill levels in the country have a significant impact on O&M costs, especially if lack of skills means that expatriates are required. Some other input costs (vehicles, fuel, etc.) also vary by country.

Regulatory regime: the cost of permits, licences, registrations, rents, and other administrative outgoings varies from facility to facility and by country.

Owners approach to staffing: many traditional public utilities carry larger staff resources than commercial organisations with leaner operations.

The cost schedules from this Step will be used in the cost-benefit analysis to validate the strategy and check whether the proposed strategy is sustainable and bankable.

Step 7: Cost-benefit analysis of proposed strategy

Carry out cost-benefit analysis to assess the economic viability of the proposed strategy. If the strategy does not pass the test for economic viability, it may be necessary to go back to Step 2 to adjust objectives, activities, and resources. Once financial viability of the proposed strategy is achieved, internal and external validation can be sought. This Step also includes a check that adequate funding will be available.

Step 8: Monitoring and key performance indicators

Implement the strategy and prepare annual and rolling five-year operating plans and longer-term capital programmes. Overall performance of the strategy will be monitored through KPIs specified in appropriate agreements and contractual arrangements. The terms and conditions in the O&M contract will need to reflect the obligations of the owner under its concession agreement and PPA in the case of an IPP, or the requirements of the electricity regulator in the case of a public utility.

Model 3 case study: Nalubaale-Kiira Hydropower Complex, Uganda

The Ugandan government, working with the Uganda Electricity Generation Company (UEGCL), awarded a 20-year operational, management and maintenance concession to Eskom Uganda Limited (EUL), a subsidiary of Eskom, to cover both the Nalubaale Power Station and the adjacent Kiira Power Station.

The concession agreement commenced in 2003, with the electricity generated being sold to UETCL; the agreement expires on April 1, 2023. In this Model 3 concession arrangement, all O&M responsibilities are assumed by EUL, the private operator, for a fixed duration. UEGCL supervises the asset health and assumes all risks that are deemed to be catastrophic in nature. The owner reports to Electricity Regulatory Authority (ERA) to enforce performance standards, especially during the periodic renewal of generation licence performance targets.

EUL, the O&M operator, assumes all operational risks and mobilises all the required capital funding to keep the assets in good condition under an investment incentive structure, based on a 12% return on investment on all verified investments (any capital replacement made by EUL is recovered through asset depreciation plus a 12% ROI) during the contract period. Utility Prudent Practices are generally the yardstick by which the assets are to be maintained. So far, no specific details of these practices have been defined in the existing contract between EUL and UEGCL due to the broad definition of prudent practices.

Under the current 20-year O&M contract with Eskom Uganda, UEGCL hasexperienced challenges and successes, which include:

Transfer of knowledge Eskom Uganda has facilitated knowledge and skills transfer to a number of trainees from academic institutions as part of the usual industrial practice of internship programmes.

Modernisation the operator has modernised some of the critical plantsystems, albeit at a slower pace than what was anticipated at contractsigning. These improvements reduced the number of forced outages at the Nalubaale Power Plant.

Due to the generic definition of prudent practices, the success of the O&M contractual arrangement with Eskom Uganda cannot be fully appraised in the absence of appropriate qualitative or quantitative assessment. Discussions are ongoing to amend the contract to improve the contractual performance measures with a focus on asset management.

Due to rapidly advancing technologies and long procurement lead times, there is an ongoing requirement to stock spare components to avoid loss ofgeneration due to forced outages.

Alkali Silicate Reaction (concrete expansion) at the Nalubaale HPP has been (and continues to be) a technical issue since 1964 when the first crack appeared, resulting in a significant reduction in the expected life of the civil structure. Therefore, a programme has been undertaken to carry out a comprehensive rehabilitation of the power station, beginning with the feasibility study already underway.

Skills retention continues to be a challenge due to ongoingindustrialisation where skilled staff are in high demand by competitors.Therefore, there is a need to continuously provide on-board training and competitive salaries to retain skilled workers.

In general, the emergence of private sector-led investment in other forms ofrenewable energy, mainly from solar PV and other small hydropower projects on seasonal rivers, has resulted in an increase in peaking requirements and start/stop cycles for the large hydropower projects on the Nile River.

This additional demand for peaking will ultimately lead to a reduction in the design life of the hydro units, particularly for Kiira HPP which was designed for baseload conditions. The impact on Nalubaale units is not seen to be as significant because the units are Kaplans and can easily follow demand; i.e., each unit has an operating range from as low as 6MW up to 18MW, providing a healthy margin of spinning reserve.

In view of these challenges, a modernisation plan for the Nalubaale-Kiira Hydropower Complex is in preparation, focusing mainly on the optimisation of the two power plants to improve their plant factor, and to find a permanent solution to concrete expansion problems at Nalubaale Power Plant. ESI

This is article is based on an adaption of the Operation and MaintenanceStrategies for Hydropower handbook, compiled by the World Bank with thesupport of the Swiss State Secretariat for Economic Affairs and in collaboration with the International Hydropower Association. License: CC BY 3.0 IGO.

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Column: Why Ahmaud Arbery deserved to live – The Augusta Chronicle

I write in response to Matthew Hutchersons letter to the editor published in The Augusta Chronicle on May 12 titled Black racism murdered Arbery.

It is indubitable that many have been stirred to emotion at the very unfortunate and equally untimely death of Ahmaud Arbery in the Satilla Shores neighborhood of Brunswick. I know I was. Nevertheless, there is absolutely nothing to doubt about the cause of his death and why it took over two months to make an arrest after his death, and I can note without fear of contradiction that what Dr. Hutcherson candidly delineates as being black racism is, in no way, responsible for the death of Ahmaud.

The letter suggests that any attempt to perpetuate black culture as a part of the pluralistic beauty of the American fabric - by way of being visible in the media and on television, while exposing the truths of the black experience in America in all facets of society - in some way fosters black racism. Stating such is both an insult and is stupefyingly color-blind to the struggles of the past that black people in America had to overcome to foster a sense of belonging and community in a country that we were forcefully brought to commencing in 1619, enslaved in, helped build and invent, defend in arms, and of which we have been fortunate as a result of the bloodshed, marches, sweat, prayers and tears of many to rise to the upper echelons of leadership.

Dr. Hutchersons comments are supremely out-of-touch with black American reality, white American reality, and reality in general in allowing the past struggles and triumphs to be our collective impetus to unite as a human race with no consideration of skin complexion and move forward. His attempts in his letter to provide an apology of Ahmauds pursuit and murder, be it an endeavor to foster unity, sows remarkable divide and refutes the beauty of the Rev. Martin Luther Kings egalitarian dream.

Dr. Hutcherson pitiably confuses his contrived black racism with what is actually black exceptionalism, which is allowed under the auspices of the Declaration of Independence of this country in its opening statements that all men are created equal and are permitted the God-given rights of life, liberty and the pursuit of happiness. How we as black people express our culture allows us to fulfill that and in no way poses a threat, as Dr. Hutcherson attempts to convey, to our individual and collective longevity as an ethnicity of people. Our culture gives us pride. Our culture gives us purpose. Our culture gives us power.

Let me tell you what killed Ahmaud. Two shotgun wounds to the chest facilitated by one also to his wrist killed Ahmaud. That ammunition was employed by two men, and they allowed their implicit biases; their mistaken knowledge of how and when to execute an antiquated citizens arrest statute; a dash of mistaken identity; and a generous helping of racism, whatever color it be, to influence them. They viewed Ahmaud as different. They viewed him as other. They viewed him as not belonging, and therein lies the notion of why they chose to take control of his body, and that they did. They construed him to be out-of-place, stood as impromptu judge and jury, and together decided a verdict for an unarmed young American male merely getting some exercise.

To suggest otherwise or falsely denote premises that Ahmaud was a victim of his own ethnicitys attempts to be a visible component of the American experience is to suggest that he had no business there anyway. It is to condone what the McMichaels did as OK. It is to permit Ahmaud Arberys death or that of any other young black person in this country going out for an innocent jog close to home.

My point is just like every other American who is entitled to life, Ahmaud too was entitled to life. Just like every other American who is entitled to liberty, Ahmaud too was entitled to liberty. Just like every other American who is entitled to the pursuit of happiness, Ahmaud too was entitled to the pursuit of happiness.

To suggest otherwise is un-American, egregious and an utter disgrace to how far weve come in the struggle of our people to achieve equality in every respect and the fullness of the American dream.

The writer is a physician who lives in Atlanta and Augusta, his hometown, part-time.

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Column: Why Ahmaud Arbery deserved to live - The Augusta Chronicle

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