The alpha/beta-hydrolase fold family of enzymes is rapidly becoming one of the largest group of structurally related enzymes with diverse catalytic functions. Members in this family include acetylcholinesterase, dienelactone hydrolase, lipase, thioesterase, serine carboxypeptidase, proline iminopeptidase, proline oligopeptidase, haloalkane dehalogenase, haloperoxidase, epoxide hydrolase, hydroxynitrile lyase and others. The enzymes all have a Nucleophile-His-Acid catalytic triad evolved to efficiently operate on substrates with different chemical composition or physicochemical properties and in various biological contexts. For example, acetylcholine esterase catalyzes the cleavage of the neurotransmitter acetylcholine, at a rate close to the limits of diffusion of substrate to the active site of the enzyme. Dienelactone hydrolase uses substrate-assisted catalysis to degrade aromatic compounds. Lipases act adsorbed at the water/lipid interface of their neutral water-insoluble ester substrates. Most lipases have their active site buried under secondary structure elements, a flap, which must change conformation to allow substrate to access the active site. Thioesterases are involved in a multitude of biochemical processes including bioluminiscence, fatty acid- and polyketide biosynthesis and metabolism. Serine carboxypeptidases recognize the negatively charged carboxylate terminus of their peptide substrates. Haloalkane dehalogenase is a detoxifying enzyme that converts halogenated aliphatics to the corresponding alcohols, while haloperoxidase catalyzes the halogenation of organic compounds. Hydroxynitrile lyase cleaves carbon-carbon bonds in cyanohydrins with concomitant hydrogen cyanide formation as a defense mechanism in plants. This paper gives an overview of catalytic activities reported for this family of enzymes by discussing selected examples. The current state of knowledge of the molecular basis for catalysis and substrate specificity is outlined. Relationships between active site anatomy, topology and conformational rearrangements in the protein molecule is discussed in the context of enzyme mechanism of action.

Read this article:

Alpha/Beta-hydrolase fold enzymes: structures, functions and mechanisms ...

Elche, Spain. April 26, 2016: Selective focus of a Rubik's cube on a computer

A hallmark of the Covid-19 pandemic is the successive waves of infection with one variant after another. Each variant appears more fit than its predecessor in terms of its ability to infect and spread in a population.

FIGURE 1: Successive waves of SARS-CoV-2 variants in the Covid-19 pandemic.

The ability of one virus to replace another is determined by its ability to evade the immune system of those previously infected or vaccinated, as well as intrinsic replication properties. It is essential to distinguish between these two properties as they work cooperatively to determine how fast a variant spreads through a population.

Most studies throughout the pandemic have focused on the ability of the virus to evade the immune system because of the importance of prior immunity. However, a few studies have investigated the intrinsic replication properties of the virus. Two recent studies have revealed previously unknown epidemiological properties.

The first by Wu et al. revealed that the incubation periods of successive variants are growing shorter. Their meta-analysis of 141 studies throughout the pandemic showed that the average incubation period of all cases was 6.57 days. For the Alpha variant specifically, the period was 5.00 days. For Beta, it was 4.50 days. For Delta, it was 4.41 days. For Omicron, it was only 3.42 days. This means later variants get the host sick sooner after the initial infection, and the virus moves much quicker from host to host.

A second paper by Reuschl et al. demonstrated that the ability of the virus to suppress interferon, the first line of defense for innate immunity, is increased amongst the latest variants.

These two properties are most likely associated with proteins other than the Spike. Specifically, the non-Spike structural proteins, namely E, M, and N, and the accessory proteins Orf3a through Orf10.

In a series of elegant experiments described by Syed et al., the Gladstone Institutes have examined the intrinsic replicative properties of the virus in the absence of the Orf proteins using a simplified virus-like particle. Virus-like particles are constructed only to contain specific proteins, allowing isolated testing of viral characteristics such as replication using luciferase enzymes to measure results.

In a previous study, the same group of researchers found that the N protein was critical to the virus replication of the Alpha variant. They found that the four mutations in most natural variants increase mRNA delivery and expression by about 10-fold, whereas other mutations such as R203M increase virus production between 50 to 150-fold, displaying the significant role the structural proteins can play in transmission pathogenesis.

Syed et al.

FIGURE 2: N Protein Enhanced Replication. (A) Map of SARS-CoV-2 N domains showing the locations of ... [+] observed mutations. Mutations that were observed to enhance signal are shown in bold. (B) RT-qPCR of supernatant collected from A549-ACE2 cells infected with WT and mutant SARS-CoV-2 at MOI of 0.1 at 24, 48, and 72 hours after infection.

In their recent study, they expand to analyze more recent variants and look at the effects of other proteins on replication outcomes, specifically, the structural proteins E, M, N, and S.

Using virus-like particles, they could individually examine the impact of mutations in each structural protein. First investigating the S protein, they found that the infectivity of the Delta Spike drops significantly compared to the ancestral B.1, whereas the Omicron Spike is roughly equivalent.

Next, they examined the N protein of the three viruses and B.1.1, which includes mutations R203K and G204R. The B.1.1 N is roughly six-fold more infectious than B.1, Delta N is 23.5-fold more infectious, and Omicron N is 26-fold more infectious, indicating the heavily mutated Delta and Omicron N proteins contribute significantly to virus infectivity.

Syed et al. then tested the M and E proteins, which is conjunction drop infectivity of both Delta and Omicron four-fold as compared to B.1. However, the Omicron M protein on its own remained as infectious as the B.1 isolate, indicating that the Omicron E protein contributes dropping infectivity.

Finally, they analyzed the different viruses with a complete set of S, N, E, and M proteins. B.1.1 was 5.3-fold more infectious than the ancestral B.1 strain, whereas Delta was only 3.7-fold more infectious, and Omicron was 4.6-fold more infectious (Figure 2).

FIGURE 3: Omicron structural gene variants alter the infectivity of SC2-VLPs. SC2-VLPs assembled in ... [+] packaging cells transformed with plasmids encoding S, E, M, and N genes and a luciferase mRNA fused to the SARS-CoV-2 packaging signal are tested for receptor-mediated cell transduction using a luciferase detection assay.

They also found that the cleavage and processing of Spike varied both between different S variants and when coexpressed with differing M and N variants. For example, Spike was less efficiently cleaved when all S, N, M, and E, were Omicron variants rather than an isolated Omicron Spike (Figure 3).

FIGURE 4: Western blot of cell lysates from cells transfected to generate VLPs stained for N, S, and ... [+] GAPDH as a loading control.

These results amplify the notion that N protein mutations play an essential role in the increased fitness of the virus. They also reveal complex interactions between the structural proteins, suggesting epistatic effects of mutated viral proteins working together to create a more infectious virus. For instance, introducing E, M, and N to an S protein may increase overall viral expression, or in some cases, it may even reduce the replication level.

These experiments add substantially to our understanding of the fitness of variants and how one virus can displace another. It involves not only immune evasion but also the ability of the virus to replicate and compensatory mutations throughout the genome that contribute to the viruss ability to spread throughout a population.

To solve a Rubik's Cube, you must have the nine pieces of each of the six sides correctly aligned. This is a good analogy for viral fitness. In addition to having optimal mutations in the Spike protein, there must also be optimal mutations in the E, M, and N proteins as well. In addition, there are many more dimensions to consider, as SARS-CoV-2 has roughly 30 proteins throughout the genome, akin to an immensely complicated 30-sided Rubiks Cube.

We await further studies that include the effects of accessory genes that are well known to play a role in the ability of the virus to counteract the immune system and possibly increase the rate of virus spread. This information would be critical to understanding current variants and what to expect from future iterations that may be more fit and possibly more dangerous or virulent.

Full coverage and live updates on the Coronavirus

Read the original post:

Solving The Question Of Covid Variant Increased Fitness Is Like Deciphering A Rubik's Cube - Forbes

This offer has expired!Be sure to follow us on Twitter for the latest deals and more. Sign-up for our newsletters and have our best offers delivered to your inbox daily.

This afternoons collection of the best Android game and app deals is now ready to go down below the fold. Our software discounts are joined by notable deals on Samsungs new GalaxyZ Fold 4 and Flip 4 as well as its Galaxy S22 Ultra LED View and Flip Covers, but for now we are focused on the Google Play price drops. Our collection is headlined by titles like Limbo, Battle Chasers: Nightwar, Legacy 2 and 3, Alpha Launcher Prime, and YoWindow Weather. Hit the jump for a complete look at todays best Android app deals.

Todays Android hardware deals are headlined by Samsungs new GalaxyZ Fold 4 and Flip 4 at up to $160 off alongside ongoing price drops on Googles all-new Pixel 6a. Just make sure you also scope out Samsungs Galaxy S22 Ultra LED View and Flip Covers while they are 25% off before you dive into deals on theSanDisk 2TB Extreme Portable Solid-State Drive and everything in our smartphone accessories roundup.

Limbo is an award-winning indie adventure, critically acclaimed for its captivating puzzle design and immersive sound and visuals. Its dark, misty spaces and haunting narrative will stay with you forever.

Add 9to5Toys to your Google News feed.Google News

FTC: 9to5Toys is reader supported, we may earn income on affiliate links

Subscribe to the 9to5Toys YouTube Channel for all of the latest videos, reviews, and more!

See the original post here:

Android app deals of the day: Limbo, Battle Chasers, Legacy 2 and 3, more - 9to5Toys

DeLorean Motor Company is back in business, announcing new vehicles for the first time in over 40 years. And of course they come with some of the styling we know and love from the Back to the Future trilogys time travel device. The Omega 2040 is a concept car that looks a lot like a spaceship version of the classic DeLorean. But on monster truck wheels. Or maybe theyre more like a Mars rover. Its a two-seater four-wheel drive electric vehicle. There are solar panels on a large black windshield that runs over the top of the car and connects to the rear window. Like the DeLorean at the end ofBack to the Future, this concept car looks like it could fold its wheels right up and fly away.

DesignTAXI brought this beast to our attention and has a bunch more photos of the concept car. As does Yanko Design.Somehow not one of them shows whether or not the Omega 2040 has those iconic gull-winged doors though. Well just have to punch the year 2040 into the time machine to see if its for sale and take one for a test drive. Check out more images of the car here.

DeLorean also announced the Alpha 5, which looks more like the classic 80s car. Gull-wing doors and all. It debuted at a fancy car show recently but wont be ready to buy until 2024. Another concept car in the lineup is the Plasmatail, which sounds like Pokmon but actually looks to be a hatchback version of the Alpha 5.

If youre not interested in owning aluxury car, there are Playmobil andLEGO versions of the classic DeLorean. And also Gigawatt, a Transformer/DeLorean/time machine combination keeping all of space and time safe from Biff Tannen and his relatives.

Melissa is Nerdists science & technology staff writer. She also moderates science of panels at conventions and co-hosts Star Warsologies, a podcast about science and Star Wars. Follow her on Twitter @melissatruth.

Excerpt from:

DeLorean's 2040 Concept Car Is Ready to Go Back to the Future - Nerdist

VANCOUVER, CANADA TheNewswire - July 07, 2022: Sitka Gold Corp. (Sitka'' or the Company) (CSE:SIG) (FSE:1RF) (OTCQB:SITKF) is pleased to provide an update on its recently initiated drill program at the Companys Alpha Gold Project (Alpha Gold or the Project), located at the southeast end of the Cortez Trend approximately 40 kilometres southeast of the Barrick/Newmont Cortez gold mine complex in Nevada.

AG22-09 and 10 have both now defined a new zone of strong alteration in a North to NNW structure. Both holes hit strong silicification in Horse Canyon equivalent stratigraphy with zones of 5 - 10+ percent pyrite, including dark, discolored, potentially arsenic-rich pyrite. Originally calcareous rocks near the fault zone are decalcified to completely karsted. AG22-10 encountered an 11.5 metre cavity. Drill results in combination with surface mapping indicate significant offset on this fault along at least two strands. AG22-10 started in the footwall of the fault and tested altered Horse Canyon equivalent there from 149 to 175 metres. The hole then crossed the fault into the down-dropped hanging wall and is now in a repeated section of strongly silicified, decalcified, pyritic Horse Canyon stratigraphy from about 232 metres. The hole remains in progress with the objective of reaching the upper Devils Gate Limestone.

Drilling at Alpha Gold continues to rapidly advance our knowledge of the Carlin-type gold system we discovered last year, stated Cor Coe, P.Geo., CEO and Director of Sitka. Visual observation of the new structural zone intersected in holes AG22-09 and -10 has us very excited as it appears to be the primary mineral control at Alpha Gold with the most robust alteration and Carlin-type mineralization observed to date. We eagerly await the results from these drill holes as we continue to vector toward the high-grade core of this Carlin-type gold system.

Shallower depths to the Horse Canyon equivalent unit confirm that this structure lies closer to the Alpha anticline axis. AG22-09 hit the target stratigraphy at 113 metres, and AG22-10 hit it at 149 metres, compared to 335 metres in AG21-08, farther east. Alteration encountered thus far in 2022 has been very robust, emphasizing the importance of this new structural zone and the company looks forward to receiving the assay results. All samples for AG22-09 and samples to 247 metres in AG22-10 have been delivered to ALS Global Labs in Elko, Nevada for analysis.

Increased alteration, greater offset, and proximity to the anticlinal crest suggest that the structure presently being tested may be the primary mineral control and the eastern structure tested last year by AG21-08 may be secondary. It also appears that AG21-06, the weakest hole in the area was well into the footwall of both structures and off target where it tested the Horse Canyon equivalent strata. Mineralization is believed to continue southward, west of that hole. Upon completion of AG22-10, the next hole will be a 950-metre southward offset to test the new structural zone near the next major E-W cross-structure (Figure 1). Confidence for this aggressive offset comes from a better understanding of the mineralization controlling fault system and definition of the anticline crest, both of which appear to be farther west than previously thought. The proposed hole will be drilled WSW, should have a favorable angle to bedding and is anticipated to hit the Horse Canyon equivalent unit at a depth of about 350 metres.

Figure 1 Location of Drill Holes -05 to -10 and Proposed Hole AG22-11

The Company is very excited to be continuing its exploration efforts at Alpha Gold, where drilling completed in 2021 discovered a new Carlin-type gold system. Valuable knowledge gained from the previous drill campaigns, along with additional mapping and other recent information gathered in the area, have been incorporated into the latest generation of priority drill targets for this current phase of exploration. All previous holes drilled to date have intersected gold mineralization associated with strong Carlin-Type pathfinder elements in a zone of strong alteration at surface that extends for approximately 7 kilometres along major fold structures that have been mapped in the area. Sitka intends to drill a minimum of 1,500 metres during this phase of exploration.

About Alpha Gold

Sitka Gold has acquired a 100% interest in the Alpha Gold Project, located along the southeast projection of the prolific Cortez Gold Trend in Eureka County, approximately 135 kilometres southwest of Elko, Nevada. The Project is comprised of 1 claim block totaling 239 lode claims covering an area of approximately 4,780 acres (1,934 hectares) and is accessible via a dirt road, approximately 2 km west of Nevada State Highway 278.

The Project was initially staked after the location was recognized as the intersection of the regional-scale Pine Valley anticline with northeasterly fold trends exposed in the Roberts Mountains. Overprinting NNW folds coincident with the projection of the Cortez Trend were subsequently recognized and found to be important alteration and mineralization controls. Of primary importance at the Alpha Gold location is that the rocks have been down-dropped significantly by late extensional faulting. Prior to extension, and during the critical 36-42 Ma Carlin-type mineralization event, the fold crest at Alpha Gold would have been a regional highpoint among nearby mountain ranges. Well exposed lower plate windows near Alpha Gold have been extensively explored for Carlin-type gold deposits with a number of deposits found along the limbs.

Three drill programs totaling 2604 meters in 8 holes have been completed at Alpha Gold since its acquisition and have advanced the Property from an undrilled geologic concept with a surface alteration and pathfinder element anomaly, to a large wide-open Carlin-type gold system with thick, low-grade gold intercepts, from wide-spaced drilling.

About Sitka Gold Corp.

Sitka Gold Corp. is a well-funded mineral exploration company headquartered in Canada. The Company is managed by a team of experienced industry professionals and is focused on exploring for economically viable mineral deposits with its primary emphasis on gold, silver and copper mineral properties of merit. Sitka currently has an option to acquire a 100% interest in the RC, Barney Ridge, Clear Creek and OGI properties in the Yukon and the Burro Creek Gold property in Arizona. Sitka owns a 100% interest in its Alpha Gold property in Nevada, its Mahtin Gold property in the Yukon and its Coppermine River project in Nunavut.

Sitka currently has three diamond drill rigs operating at its RC Gold Project in the Yukon where it is focused on step out drilling at the newly discovered Blackjack Zone (see news release dated December 13, 2021) and to date has completed 12 drill holes in 2022 totalling approximately 3600 metres. Drilling is also currently underway at the Companys Alpha Gold Property in Nevada where up to 1500 metres of drilling is planned.

*For more detailed information on Sitka and its underlying properties please visit http://www.sitkagoldcorp.com

The scientific and technical content of this news release has been reviewed and approved by Cor Coe, P.Geo., Director and CEO of the Company, and a Qualified Person (QP) as defined by National Instrument 43-101.

ON BEHALF OF THE BOARD OF DIRECTORS OF

SITKA GOLD CORP.

Donald Penner

President and Director

For more information contact:

Donald Penner

President & Director

778-212-1950

dpenner@sitkagoldcorp.com

or

Cor Coe

CEO & Director

604-817-4753

ccoe@sitkagoldcorp.com

Cautionary and Forward-Looking Statements

This news release contains forwardlooking statements and forwardlooking information within the meaning of applicable securities laws. These statements relate to future events or future performance. All statements other than statements of historical fact may be forwardlooking statements or information. Forwardlooking statements and information are often, but not always, identified by the use of words such as appear, seek, anticipate, plan, continue, estimate, approximate, expect, may, will, project, predict, potential, targeting, intend, could, might, should, believe, would and similar expressions.

Forward-looking statements and information are provided for the purpose of providing information about the current expectations and plans of management of the Company relating to the future. Readers are cautioned that reliance on such statements and information may not be appropriate for other purposes, such as making investment decisions. Since forwardlooking statements and information address future events and conditions, by their very nature they involve inherent risks and uncertainties. Actual results could differ materially from those currently anticipated due to a number of factors and risks. These include, but are not limited to, the expected timing and terms of the private placement, use of proceeds, anticipated work program, required approvals in connection with the work program and the ability to obtain such approvals. Accordingly, readers should not place undue reliance on the forwardlooking statements, timelines and information contained in this news release. Readers are cautioned that the foregoing list of factors is not exhaustive.

The forwardlooking statements and information contained in this news release are made as of the date of this news release and no undertaking is given to update publicly or revise any forwardlooking statements or information, whether as a result of new information, future events or otherwise, unless so required by applicable securities laws or the CSE. The forward-looking statements or information contained in this news release are expressly qualified by this cautionary statement.

Neither the CSE nor its Regulation Services Provider (as that term is defined in the policies of the CSE) accepts responsibility for the adequacy or accuracy of this release. No stock exchange, securities commission or other regulatory authority has approved or disapproved the information contained herein.

Read more:

Sitka Gold Provides Update on Drilling at its Alpha Gold Project in Nevada - TheNewswire.ca

BA.2.75 as a dark horse.

Far from concluding, the Covid pandemic seems to be picking up speed with new variants. The BA.5 variant is spreading rapidly in Europe and North America, potentially infecting as many or more people as the original Omicron virus from which it is derived. A second variant, BA.2.75, has been detected in India and is rising quickly. We have previously described BA.4 and BA.5; here, we focus on the novel BA.2.75.

Omicron BA.1 variant emerged in late 2021 with substantial genetic and virological differences. BA.1 was quickly followed by the genetically distinct descendant BA.2. Figure one denotes the initial rise of BA.1, quickly followed by BA.2. These represented the bulk of cases during the winter months of early 2022 when confirmed cases in the United States peaked at around 1 million per day. BA.4 and BA.5, which are very similar, derive from BA.2, as does BA.2.75, although independently. There is no relation between Omicron BA.1 and the other major variants, Alpha, Beta, Gamma, Delta, etc. BA.4/BA.5 is the dominating strain of Covid-19 today, and we believe BA.2.75 may join them.

FIGURE 1: BA.2.75 was independently derived from BA.2, significantly differing from BA.4 and BA.5.

FIGURE 2: Cases in the United States designated by variant type.

Later Omicron variants, such as the currently dominating BA.4 and BA.5 strains, appear capable of reinfection of those previously infected with an earlier strain. Those infected with BA.1 were susceptible to BA.2, and so on. One report indicates that BA.5 was between 14.3 and 16.8-fold more resistant to Evusheld and Sotrovimab antibody treatments than previous variants. This resistance, in addition to new mutations, is likely related to sensitivity to a membrane protease, TMPRSS2, that is associated with cell membrane infectivity. BA.5 has a greater sensitivity to TMPRSS2 inhibitor Nafamostat, meaning that BA.5 is slightly less infectious relative to BA.1 and BA.2, but could be more virulent and immune evasive, akin to the Delta variant of 2021.

FIGURE 3: (A) Shift in linear regression between virus infectivity and diagnostic PCR Ct values ... [+] gives a measure of TMPRSS2 use by individual variants (B-D) Primary nasopharyngeal swabs were used to inoculate the HAT-24 cell line. Cultures of (B) AY39.1 (one of the last detected Delta lineages), (C) BA.2 and (D) BA.5 imaged 72 hours post-infection. (D) Infectivity for BA.2 and BA.5. (F) Virion particle counts for three early clade variants (A.2.2, Beta and Delta) and three Omicron sub-lineages (G) Schematic showing the effect of TMPRSS2 inhibitor Nafamostat on virus entry at the cell membrane. (H) The efficiency of TMPRSS2 usage by the virus.

The latest in the line of Omicron variants is BA.2.75, which has a distinct set of Spike mutations in addition to those found in BA.2, BA.4, BA.5, and other mutations outside the Spike protein, indicating it was independently derived from BA.2.

BA.4 and BA.5 are very similar, differing by only a few mutations in the structural proteins N and M, nonstructural protein NSP4, and accessory proteins Orf6 and Orf7b, as described in a previous discussion (Figure 3). These differences seem to grant BA.5 a replication advantage, outpacing BA.4 in North America and Europe (Figure 2). Both silent and amino acid altering mutations in the Orf1ab replication complex, structural proteins, and accessory genes can increase the viral fitness of SARS-CoV-2. It remains to be determined which mutation grants BA.5 the replication advantage it possesses.

FIGURE 4: Non-Spike protein mutations in BA.4 and BA.5

BA.2.75 is still very new. It was recently discovered in India, followed by ten countries soon after. The World Health Organization has already warned about BA.2.75 and continues to monitor the variant as it spreads to more regions of the globe. While confirmed cases due to BA.2.75 are relatively low, numbers are expected to increase in the coming weeks.

Not only is BA.2.75 a derivative of BA.2, but it is distinct from BA.4 and BA.5.

FIGURE 5: Venn diagram comparison of BA.4/BA.5 mutations versus BA.2.75. Those on the left are ... [+] unique to BA.4 and/or BA.5, those on the right are unique to BA.2.75, and those in the middle are shared between the two strains.

The Spike is the most heavily mutated protein in the Omicron family of variants. This pattern holds with BA.2.75. There are 36 mutated amino acids in the BA.2.75 Spike protein. Some early variants, such as Alpha, did not even carry 36 amino acid mutations in the entirety of their genome. BA.2.75 has this amount in the Spike protein, which accounts for roughly 10% of the SARS-CoV-2 genome.

FIGURE 6: BA.2.75 Spike protein mutations. Those in red are found in BA.2.75. Those in blue are ... [+] unique to BA.2.75, meaning they are not in BA.2. The sole mutation highlighted in green indicates that the position was reverted from Q493R back to Q493 in BA.2.75. Those in black are not found in BA.2.75 or BA.2 but are found in other Omicron strains.

The unique mutations of the BA.2.75 Spike protein are isolated to the N-terminal and receptor-binding domains. These are regularly the most heavily mutated regions of the virus as they are typical targets for neutralizing antibodies derived from infection, vaccines, and monoclonal treatments, meaning mutations may allow the virus to overcome neutralization. These regions also play a significant role in the viruss transmissibility, speaking to how later variants grow more infectious.

The new additions fall into two categories: new mutations and reversions. We only find one reversion in BA.2.75, which is Q493. In BA.2, this position was mutated from glutamine to an arginine (Q493R), a common mutation in circulating variants throughout the pandemic. Reversions are uncommon, as a mutation often confers some virological advantage over the original amino acid. However, this reversion may interact complimentarily with a new unique mutation to confer a more significant advantage than Q493R could have on its own.

Aside from the reversion, there are eight mutations in the BA.2.75 Spike that are unique from BA.2. In addition, all but one of these eight mutations (K147E, W152R, F157L, I210V, G257S, G339H, and N460K) are uncommon in any previous variant of concern or interest.

We note that F157L was previously detected in a minor African strain A.23.1. Mutations occur at position I210 in the African A.30 and French B.1.640 strains but to different mutations (I210N and I210T, respectively). Additionally, position W152 is mutated in the Epsilon strain of 2021, but to W152C.

To have such unique mutations at this stage of the pandemic when the virus has mutated into hundreds, even thousands of competing strains is astounding. These mutations likely have health officials on high alert, as a wealth of new mutations could indicate increased transmissibility or immune evasion if the variant catches fire like its predecessor.

The new lineage also has five new additions outside of the Spike protein. Four lie in the Orf1ab replication-transcription complex, and the last lies in the Envelope protein.

FIGURE 7: BA.2.75 mutations outside the Spike protein. Those in red are found in BA.2.75. Those in ... [+] blue are unique to BA.2.75, meaning they are not in BA.2. Those in black are not found in BA.2.75 or BA.2 but are found in other Omicron strains.

Two of the unique mutations, S403L and P822S, lie in NSP3. This protein is involved in the formation of the structure of the double-membrane vesicle replication compartment. It also inhibits interferon activity by direct cleavage of IRF3 and antagonizing MDA5 activation. These mutations could therefore be involved in virus replication and immune evasion activities.

We additionally note N118S in NSP8, G671S in NSP12, and T11A in the Envelope protein. NSP12 is the RNA polymerase that drives viral replication and transcription, while NSP8 is a structural cofactor for that machinery. The Envelope is involved in viral assembly, budding, and viral porin activity. More research is needed on these unique mutations to determine their exact advantages, but they are likely involved in these processes. You can read more about the functions of each protein in our book Natural Immunity.

There may be several mutations that do not change amino acids in the coding sequence, known as synonymous mutations, but we do not have access to those at this time.

Even as we write this article, the Omicron family is ever-evolving. In addition to BA.2.75, recent reports from India suggest that there are accompanying lineages BA.2.74 and BA.2.76 that are circulating concurrently with BA.2.75. As of yet, the exact sequences are unavailable to view on the GISAID SARS-CoV-2 database, though the researchers suggest they share the same Spike protein, implying that differences lie outside the Spike just as BA.2.75 differs from earlier variants.

To summarize, having just recovered from the first Omicron wave of BA.1 and BA.2 at the start of the year, as well as the BA.2.12.1 wave in the United States and elsewhere, the world is now facing two additional variants, which may individually or collectively surpass the first wave in magnitude. In the United Kingdom epidemic alone, infections jumped several hundred thousand in previous weeks due to the new strains. Were the US to face similar increases, daily rates could be in the millions, exceeding the peak of the Omicron wave in mid-January. The impact of BA.5 and BA.2.75 on health outcomes, hospitalization, and death remains to be seen. All countries but China have abandoned public mitigation measures, meaning Covid safety now falls on the individual, which is a sorry state of affairs in the face of the continued onslaught of SARS-CoV-2.

Full coverage and live updates on the Coronavirus

More here:

BA.2.75: A Dark Horse In The Covid Pandemic - Forbes

Amicus Therapeutics, Inc. (NASDAQ:FOLD Get Rating) CEO John F. Crowley sold 11,346 shares of the businesss stock in a transaction on Friday, July 1st. The stock was sold at an average price of $10.78, for a total transaction of $122,309.88. Following the completion of the sale, the chief executive officer now directly owns 910,993 shares of the companys stock, valued at $9,820,504.54. The transaction was disclosed in a legal filing with the Securities & Exchange Commission, which can be accessed through this hyperlink.

FOLD opened at $11.19 on Friday. The firm has a market capitalization of $3.14 billion, a price-to-earnings ratio of -11.54 and a beta of 1.07. Amicus Therapeutics, Inc. has a one year low of $5.91 and a one year high of $12.63. The business has a 50 day simple moving average of $8.48 and a two-hundred day simple moving average of $9.09. The company has a debt-to-equity ratio of 1.63, a current ratio of 4.00 and a quick ratio of 3.81.

Amicus Therapeutics (NASDAQ:FOLD Get Rating) last announced its quarterly earnings results on Monday, May 9th. The biopharmaceutical company reported ($0.30) EPS for the quarter, missing analysts consensus estimates of ($0.24) by ($0.06). The business had revenue of $78.72 million during the quarter, compared to analysts expectations of $76.97 million. Amicus Therapeutics had a negative return on equity of 95.05% and a negative net margin of 84.97%. During the same period in the previous year, the business earned ($0.25) EPS. As a group, sell-side analysts expect that Amicus Therapeutics, Inc. will post -0.89 EPS for the current fiscal year.

Several research analysts have recently commented on the company. StockNews.com assumed coverage on Amicus Therapeutics in a report on Thursday, March 31st. They issued a hold rating on the stock. The Goldman Sachs Group started coverage on Amicus Therapeutics in a research note on Wednesday, April 13th. They set a neutral rating for the company. Two investment analysts have rated the stock with a hold rating and five have assigned a buy rating to the stock. According to MarketBeat, the company presently has a consensus rating of Moderate Buy and a consensus target price of $15.20.

About Amicus Therapeutics (Get Rating)

Amicus Therapeutics, Inc, a biotechnology company, focuses on discovering, developing, and delivering medicines for rare diseases. Its commercial product and product candidates include Galafold, an oral precision medicine for the treatment of adults with a confirmed diagnosis of Fabry disease and an amenable galactosidase alpha gene variant based on in vitro assay data.

Featured Articles

Receive News & Ratings for Amicus Therapeutics Daily - Enter your email address below to receive a concise daily summary of the latest news and analysts' ratings for Amicus Therapeutics and related companies with MarketBeat.com's FREE daily email newsletter.

See original here:

Amicus Therapeutics, Inc. (NASDAQ:FOLD) CEO Sells $122309.88 in Stock - Defense World

You knowwhat would be a better title, Joe Jaffe says to me after I tell him I might use that headline for an article about him, The Second Life Of Joe Jaffe.

Jaffe wasright. For two reasons.

The first is because its about Jaffe getting a second chance at life after undergoing a series of life-threatening events (open-heart surgery that ledto multiple infections and hospitalizations, and then a serious case of COVID-19) that led to a business-ending one causing him to fold brand consultancy HMS Beagle, which ironically was supposed to help brands learn how tosurvive.

The other reason its a better headline for this story, is because Second Life works as a double entendre, because Jaffes next new thing is a lotlike an old new thing the Second Life virtual reality platform that was supposed to help launch brands into the metaverse.

Jaffe, if you dont recall, was a consultant15 years ago that helped develop a Virtual Thirst presence for Coca-Cola on Second Life that led to an article in Wired magazine criticizing big brands for pouring money into avirtual reality platform that had virtually no people on it.

But this time around, the main brand Jaffe is promoting in the metaverse and vis a vis other Web3 incarnations is his own.

Im all in on Web3, he says, adding, The only way you can buy my time is through an NFT.

Jaffe, who has beenminting himself via a Rally.io creator coin aptly named Jaffe Coin, is in the process of creating what he says is his biggest idea ever, and which all his past incarnations his books about multiple next new things, his public speaking, his pioneering agency (Crayon), and serial big idea consultingprojects.

Jaffe is in the process of minting a 1,000 NFTs that will be the only way anyone can access a new premium subscription service dubbed Alpha Collectivelaunching Sept. 12 that will include a weekly series of mastermind talks connecting big brands with big Web3 ideas, and the people developing them, as well as a a variety of premiumevents virtually and in real life as well as still undisclosed premium swag for participating as founding members.

True to his promise of being all in on Web3, Jaffesays the NFTs can be redeemed as long as owners want to access Alpha Collective, but can also be resold in secondary markets based on what those markets can yield.

Imbasically using the NFTs as a digital membership pass to an exclusive premium community, he explains.

Jaffe is offering 1,000 NFTs for $2,500, which if you do the mathis $2.5 million, he says, adding that it isnt all going to his personal bottom line, but will be reinvested in various parts of the Alpha Collective community, including producing thein-real-life events, other premium swag and experiences, as well as 100 ETH (Ethereum coins, which currently fetch more than $1,000 on crypto exchanges) that he will use to pay back the community andfund various projects developed through it.

After Sept. 12, the only way youll be able to buy my time is via an NFT, he says, adding, Im giving upspeaking. Im giving up consulting. Im all in on Web3.

Jaffe is so in, that owners of those NFTs can sell them to others giving them access to Jaffe for otherprojects they want to work on.

There are more moving pieces to the Web3 versioning of Jaffe, who says that except for some college classes he teaches, is basically destitute and insearch of new revenue.

The truth is he has other projects in the works, including his weekly podcast Joseph Jaffe Is Not Famous, which he calls The Daily Showfor Business, and has high hopes of licensing to a big video platforms such as Hulu, HBO Max, CNBC or Cheddar.

But other than that, his teaching gigs, andwhatever else might come along IRL, Jaffe says the only way to access his mastermind is by owning and NFT giving people access to the Alpha Collective.

Jaffeacknowledges that the timing of his launch coming amid a cryptocurrency crash, and a mounting backlash to some forms of initial Web3 marketing, including branded NFTs isntnecessarily the best, but he says the ideas underlying it are sustainable, and only a matter of time before they manifest and begin to scale for marketers.

Web3 has turnedover more in a year than social has done in 10 and digital has done in 25, he asserts, noting that he began predicting the emergence of universal brand currency more than a decadeago, and envisioned a time when Nike would have a swoosh coin and Coca-Cola would have a ribbon token, which is the way many marketers are experimenting with NFTs now in order to giveconsumers access to exclusive, premium brand experiences.

The new permission marketing is an NFT, because once you buy into that, you are all in, Jaffe says about thevalue those smart contracts can create for the marketer, not just the consumer. And the minute you sell that NFT, you are opting out.

During a series of Zoom-basedinterviews with Jaffe, he repeated how everything he has done has led up to Alpha Collective, and how it is his biggest idea, and I remind him that he has said the samething about most of the previous projects Ive interviewed him on in his past.

And I was right almost every time, he says, then corrects himself: Maybeevery time.

See the original post:

The Second Coming Of Joe Jaffe 07/11/2022 - MediaPost Communications

Sometimes, being the top player at a position on your team is more of a reflection of your teams lacking talent versus your abilities. Thats certainly the case every year in the NFL, specifically at the wide receiver position. While its great to target top options in offenses, sometimes its more fruitful to draft secondary targets on good offenses versus primary targets on bad offenses. Lets take a look at WR2s that are currently being drafted ahead of the last WR1 in 2022 fantasy football rankings (Jakobi Meyers).

Tee Higgins (CIN)

Tee Higgins 23% target rate per route run was higher than JaMarr Chases 21% during the 2021 regular season as was his 25% target share in the games they played together when healthy.

Theres no denying that WR1 overall upside exists with Chase in 2022, but Higgins constant command of targets in a loaded Cincinnati offense will make him a screaming value in 2022 fantasy drafts.

Jaylen Waddle (MIA)

Jaylen Waddle looked primed to make the leap into the top-12 conversation after a stellar rookie season. Along with breaking Anquan Boldins rookie reception record, Waddle commanded a 22% target share and 24% target rate per route run 18th-best in the NFL.

But with the expensive addition of veteran Tyreek Hill, it is less likely that Waddle is the clear-cut No. 1 receiver in Miami. Hill is coming off a season where he commanded the leagues seventh-highest target rate per route run (27%). The trade moves Waddle down from a fringe WR1 to mid-range fantasy WR2 after seeing almost zero target competition last season.

Mike Williams (LAC)

Mike Williams had the opportunity to take his talents elsewhere this offseason in free agency, but decided to stay in Los Angeles with quarterback Justin Herbert. Hard to argue with the choice to sign a three-year deal worth $60M attached to a young superstar quarterback, especially when that quarterback fueled a career year.

He stormed out the gate in 2021 as the WR2 in fantasy through the first five weeks of the season, averaging 94.2 receiving yards and 1.2 receiving touchdowns per game.

Big Mike finished the season as the WR23 in fantasy points per game despite cooling off considerably in the later weeks in addition to leaving a boatload of touchdown production on the table.

He finished sixth in end-zone targets (16) but caught only five for touchdowns.

With positive TD regression on his side, Williams looks like a sneaky candidate to repeat his WR12 overall finish in the half-point scoring format.

Jerry Jeudy (DEN)

Entering Year 3, Jerry Jeudy finally has a quarterback who can take full advantage of his ability to separate from defenders 96th percentile separation percentage in 2021 with Russell Wilson taking the reins.

With Courtland Sutton and Tim Patrick operating from the outside, Jeudy figures to become Wilsons go-to target in the slot unless K.J. Hamler pushes him out. Jeudys efficiency metrics should also see a massive boost now that hes catching passes from a future Hall-of-Fame quarterback, but it remains to be seen if Jeudy will play an ancillary role as a red-zone threat.

Upgrading from Drew Lock and Teddy Bridgewater to Wilson is great for Jeudy, but we have to remember that he is still an unproven fantasy commodity. Great route-running and separation skills aside, he hasnt scored many fantasy points the last two seasons.

And thats not the case with every Denver receiver, because Patricks production last two seasons earned him a three-year, $34.5 million contract extension.

Even so, Jeudy should easily experience his best NFL season to date in 2022, but it may not be as great as some die-hard Jeudy stans would care to admit. There are a lot of weapons in Denver, and predicting Wilsons best option on a week-to-week basis was often a challenge when it was only between DK Metcalf and Tyler Lockett.

As with those Seahawks receivers, there are going to be inconsistent weeks from Jeudy. And his lack of red-zone usage makes him more susceptible to bust games without having a touchdown opportunity to fall back on.

Allen Robinson II (LAR)

Before Robert Woods hit the IR, he was the WR17 in half-PPR scoring per game. Van Jefferson saw elite usage playing on every down as the No. 3 receiver but didnt follow up his playing time with any worthwhile production. Jefferson was WR35 overall on the season and outside the top 40 in points per game despite a top-tier 86% route participation.

The likely scenario for Allen Robinson is that he steps up into the No. 2 role behind Cooper Kupp and operates the way Woods started the year and/or by how Odell Beckham Jr. ended the season.

Down the playoff stretch, Beckham Jr. averaged a 19% target share and 12.4 fantasy points per game from Week 12 through the divisional round (fantasy WR2).

Chris Godwin(TB)

Chris Godwin posted another stellar season last year as the WR7 in fantasy football. He set opposing defenses on fire as Tom Bradys underneath weapon, ranking eighth in YAC per reception and fifth in overall YAC yardage. The biggest question for Godwin in 2022 isnt talent but his recovery from an ACL and MCL tear sustained in Week 15 of last season. If Godwin is good to go, hes a top 15 fantasy wideout, but tempering expectations early on if hes limited or starts on the PUP pushes him into WR2/WR3 territory based on possible time missed.

Gabriel Davis (BUF)

Gabriel Davis averaged 19.8 fantasy points per game (PPR) and 16.0 expected fantasy points per game in his last six games while running a route on 88% of dropbacks as the Bills finally emphasized his playing time in the offense.

As a strong bet to earn the No. 2 wide receiver job come opening day, Davis has a legitimate shot to be a reliable fantasy option in a Josh Allen-led offense in 2022.

Adam Thielen (MIN)

The 32-year-old wideout has made his hay in fantasy because of his ability to find the end zone 24 times since the start of 2020, but its something that just isnt sustainable in the long term. Based on Thielens targets and yardage totals, his total TD number should be closer to 16.

Justin Jefferson is an ascending rocketship that will only see his TDs rise entering Year 3, most likely coming at the detriment of Thielen. Not to mention, ATs age may finally be catching up to him after he posted his lowest PFF receiving grade and yards per route run since he first became a starter back in 2016.

DeVonta Smith (PHI)

DeVonta Smith didnt have the record-breaking rookie seasons like JaMarr Chase or Jaylen Waddle, but he was still extremely solid. He finished 10th in overall team air yards share and top-20 in PFF receiving grade among WRs with at least 100 targets.

So Smiths WR29 finish and WR42 standing in points per game hardly does the rookie justice while playing in a run-heavy offensive attack. From Week 7 onward, Smith never saw more than six targets in any game.

I dont necessarily believe that Smiths targets per game will increase substantially after the team added A.J. Brown this offseason; that puts Smith firmly in the fantasy WR3 tier.

Tyler Lockett (SEA)

I cant cultivate a likely scenario where the Seattle Seahawks wide receiver accrues any type of worthwhile fantasy value in 2021.

He is turning 30 years old this season and finds him in a situation with Geno Smith/Drew Lock at quarterback. Locketts infamous for his roller-coaster production four top-5 finishes, seven outside the top-36 in 2021 and I expect no less based on his current situation in 2022. The major difference is the bad games will be more frequent than ever with the massive QB downgrade.

Lockett averaged just 9.0 fantasy points per game (47th) without Wilson last season.

With Lockett competing for targets alongside Metcalf in a run-heavy offense, he looks like a straight-up fade unless his ADP falls dramatically.

Hunter Renfrow (LV)

Theres really not much left to say when it comes to Hunter Renfrow. The kids a certified stud and doesnt get the respect he deserves. The Raiders slot receiver hung a WR13 overall finish last season due to a spectacular late-season surge.

He went over 100 receiving yards in three straight games (Weeks 12-14) while maintaining a 25% target share.

From Week 12 onward, his production generated a WR8 standing in half-point scoring.

Renfrow made the most of the opportunities he got in 2021, and that wont change in 2022. Adding Davante Adams and Darren Waller will make targets for Renfrow harder to come by, but stay rest assured that the shifty wideout will perform if either guy is forced to miss time.

DeAndre Hopkins (ARI)

DeAndre Hopkins wasnt completely washed last season, but his days as an elite alpha wide receiver could be over. Last season he was the WR21 in fantasy points per game as he logged his first season since 2017 outside the top 20 in targets per snap. Hopkins only commanded a 20.5% target share which was good for 35th among wideouts. While the suspension should ensure that Hopkins will return fully healthy, its not a sure thing that we dont see his numbers decline further in 2022. He ranked 31st in yards per route run last season (minimum 50 targets, per PFF).

Brandon Aiyuk (SF)

Fantasy managers are still trying to figure out what went wrong with Brandon Aiyuk during the first half of last season. He was hyped up after an impressive rookie campaign but suffered a hamstring injury during training camp that made him unreliable in the starting offense. Through Weeks 1-7, Aiyuk had just one weekly finish inside the top-25. He also averaged an abysmal 0.63 yards per route run a mark that ranked 98th out of 102 qualifying WRs. Woof.

But give credit to Aiyuk for turning his season around during the second half. His yards per route run increased substantially (2.16, 13th) and he averaged 13.1 PPR fantasy points per game as the WR24.

If Aiyuk can roll over his second-half production into 2022, he could end up as a smashing fantasy value in a similar way that Deebo Samuel was viewed in 2021.

Robert Woods (TEN)

Robert Woods was traded to the Titans after the Rams signed Allen Robinson in free agency. The move was less about Woods ability, but rather his salary cap hit that the Rams were looking to free themselves from.

Still, entering his age 30-season fantasy managers should question whether Woods has the juice left to continue producing for fantasy. Often viewed as a safe fantasy WR2 during his time in L.A. he was WR17 before his injury in 2021 Woods might be subject to some poor game conditions in the Titans run-heavy approach that could nuke his weekly fantasy appeal.

Hes got a chance to be the No. 1 receiver if rookie Treylon Burks fails to hit the ground running, but anything less will not be fruitful for the seasoned veteran.

Over the past two seasons, production has not been kind to WRs over 30 years old. Only three receivers over 30 Cole Beasley, Adam Thielen, and Marvin Jones Jr. finished as top-40 fantasy options. If he stays healthy, Woods could easily beat his ADP.

But Im just not sure how high his fantasy ceiling is based on the situation.

Chase Claypool (PIT)

Chase Claypools second-year breakout was inevitably halted by Ben Roethlisbergers lack of downfield throwing ability: On throws with 20-plus air yards, Big Ben graded 31st out of 38 qualifying QBs.

Claypool commanded a 27% air yards share on the season and led the team in the metric over the final four weeks. Better days should be ahead of the Notre Dame product if Pittsburgh can get better downfield quarterback play from Kenny Pickett/Mitchell Trubisky.

Claypool is also due for positive touchdown regression after catching just one of his 12 end-zone targets last season. The 6-foot-5 monster is no stranger to hitting paydirt, after being one of eight wide receivers to score double-digit touchdowns as rookies since 1998.

However, Claypools range of outcomes is quite wide heading into his third season with 2022 second-round pick George Pickens, chomping at the bit to be the No. 2 on the offense behind Diontae Johnson.

Garrett Wilson (NYJ)

After enjoying a breakout sophomore campaign in 2020 that saw Garrett Wilson earn a 34% dominator rating which considers the number of touchdowns and receiving yards a player commands within their offense at 20 years old, the Ohio State product ran it back in impressive fashion in 2021.

The Buckeye scored 12 receiving touchdowns, compiled over 1,000 receiving yards and generated the FBS 12th-highest passer rating when targeted (141.7).

He also proved to NFL teams that he was more than just a shifty slot receiver, averaging 3.00 yards per route run despite operating on the outside on 83% of his routes run, which nearly matched his same yards per route run average from 2020 when he spent most of his time inside.

And although Wilsons 2021 24% dominator rating was less than his sophomore campaign, thats really due to Ohio States talent in the wide receiver room. He was competing for targets with senior Chris Olave and sophomore standout Jaxon Smith-Njigba, who led the nation in PFF receiving grade (91.7).

Going beyond the box score reveals that Wilson is a versatile route runner who can align anywhere on the field and still win.

He was selected by the New York Jets 10th overall and joins a somewhat crowded WR room. And nobody can be sure Zach Wilson can support one or multiple fantasy assets. There are definitely question marks.

However, Wilson is worth betting on because hes shown the ability at Ohio State to command targets and produce in an offense littered with other elite talents. Doesnt hurt his chance that he was deemed open on 84% of his targets last season.

Michael Gallup (DAL)

Michael Gallups late-season injury will almost certainly hurt his chances of being available for Week 1, with some diagnoses saying the Cowboys WR wont be ready until October.

The 2018 third-rounder averaged just 10.2 fantasy points per game in 2021 (47th), less than his 2020 season (10.8).

It doesnt help Gallups case either that the team re-signed tight end Dalton Schultz, who figures to compete for top targets with CeeDee Lamb. Third-round rookie Jalen Tolbert also figures to get plenty of reps in training camp with Gallup rehabbing.

Be careful to not overinvest in Gallup for fear that youll be wasting a roster spot for a player that falls into the fantasy WR3 with upside tier, that just doesnt move the needle.

Chris Olave (NO)

Even with Michael Thomas presumably back in the fold, there was still a gaping hole at the wide receiver position in the Big Easy. Long-time general manager Mickey Loomis has had zero issues spending high-end draft capital on WRs in the past, so its not surprising the Saints traded up to draft Chris Olave at No. 11.

The former Buckeye doesnt offer the same skill set as Thomas, but he can separate from defenders at an elite level downfield. Olave wrapped up his 2021 season in the 96th percentile in separation versus single coverage and caught seven touchdowns on throws of 20-plus air yards.

Olave draws parallels to Calvin Ridley with his impressive route running ability. But like Ridley coming out of school, Olave doesnt offer much after the catch.

His forced broken and missed tackle rate ranked 43rd among 43 qualifying wide receivers in the class. His yards after the catch per reception (4.2) ranked 37th.

Without much YAC-ability in an offense that ranked fifth in that YAC/reception last season and a firm seat in the WR2 chair behind a healthy Thomas, I have trouble getting overly excited for Olave in New Orleans as nothing more than a boom-or-bust WR4.

Subscribe: Apple Podcasts | Spotify | Google Podcasts | Stitcher | SoundCloud | iHeartRadio

If you want to dive deeper into fantasy football, be sure to check out our award-winning slate of Fantasy Football Tools as you navigate your season. From our Start/Sit Assistant which provides your optimal lineup based on accurate consensus projections to our Trade Analyzer which allows you to instantly find out if a trade offer benefits you or your opponent weve got you covered this fantasy football season.

View original post here:

WR2s Drafted Ahead of WR1s (2022 Fantasy Football) - FantasyPros

The Hubbis Asian Wealth Solutions event took place in Singapore on June 8, during which Christopher Tanchou and Claire Tan, both Business Development Directors of Swiss Life Global Solutions, offered delegates an interesting presentation on how wealth management advisors can help create awareness of life insurance solutions to add extra value to their relationships. They explained how these RMs and advisors can help by discussing real-life scenarios on how insurance solutions meet evolving clients needs and can help guide those clients towards working with the experts that will curate and deliver the best solutions. They focused their attention largely on Variable Universal Life and its particular advantages.

Claire Tan opened the presentation by explaining that Swiss Life is one of the largest companies in Europe, with a history of over 165 years and in 2021 produced net profits of CHF1.2 billion from some 17000 advisors and had more than CHF102 billion of client assets under management. Moreover, the company is very robust financially, with a well-performing share price over the past decade plus, and a credit rating of A+ stable from S&P.

Chris and I come from the Swiss Life Singapore entity, which focuses solely on creating life insurance solutions tailored to high-net-worth individuals, Claire reported. We have three flagship solutions. The first is VUL called Alpha Plus. Then we have our PPLI, which is called Life Asset Portfolio or LAP in short. And last but not least, we have our hybrid solution, which is basically a life insurance policy with a flexible coverage. Each of these solutions are for clients with different needs and concerns.

Christopher then explained that client needs continually evolve and regulation constantly changes, always becoming more intensive. He particularly highlighted the tightening around CFC and CRS, both of which developments have further encouraged private clients to take out new life structures for transparency and protection.

He addressed the main concerns amongst clients, including the vital reporting obligations, so often linked to tax and income. Reporting can be actually a nightmare for some clients, for example Indonesia has a worldwide taxation system so imagine those clients having to report line by line across assets and accounts worldwide, he said.

Cross border compliance is another major concern. Mobility is very important, and we see that many clients are actually moving from one country to another, with a lot in this region relocating to Singapore, for example, he observed.

You don't want your clients to set up a structure or to buy a policy or solution which is not sustainable, may not be efficient, or even well organised for the future, he cautioned delegates. You want something that can last actually for the next 20, 30, 40 years.

Succession planning is another key concern and objective, he noted, explaining how effective life solutions can be in effecting smooth transitioning of wealth and control amongst the generations.

And simplicity is a major appeal, he reported. Clients are not looking for anything complex anymore, they are not looking at several layered structures these days, he explained. They want something which is actually straightforward, easy to understand, but also easy to explain.

Claire then mined down into the advantages of VUL. She said VUL is a well-recognised life insurance policy across every jurisdiction around the world, regardless of whether the jurisdiction is based on common or civil laws.

VUL provides robust asset protection from creditors and helps with succession and efficient wealth transfer. Clients can maintain control over investment strategies, they can defer taxation until distribution to provide efficient portfolio growth, and the structure offers simplified reporting, especially in the brave new world of CRS.

Christopher then focused on how the wealth industry incumbents can help their clients by bringing VUL to the conversations. Engaging your clients with these types of ideas is essential, he said.

Claire explained: We like to position VUL with clients as a multipurpose vehicle that not only offers wealth accumulation benefits but also wealth protection benefits in the form of high death coverage, and not forgetting, there's also the benefit of wealth distribution, because the policy allows the client to nominate beneficiaries in a private confidential manner, as mentioned earlier, and therefore bypassing probate.

Christopher added that he likes to present VUL as a safety hedge against market volatility and asset price rises and falls. Without VUL, a client owning a USD20 million portfolio today, if the client passes away, the estate value will simply actually follow the market trend, and either be up or down based on market prices. So, the estate is completely affected and impacted by the markets. But with a well-designed VUL structure acquired with Swiss Life, for example, the client is always more covered and more protected. The beneficiaries will always end up getting more, regardless of the market trends. So, you can use these ideas to engage your clients.

He added that it is also possible to connect to clients via alignment with ESG-centric objectives they might have. You can nicely combine insurance with ESG mandates, to give wealth to the next generations in an ESG compliant manner, he explained. That makes a nice story.

Another advantage is, for example, using low LTV assets that are not truly optimised. Those types of lowly geared assets are often just sitting idle, so they could instead be used as assets by Swiss Life to offer substantial coverage, he explained. Claire added that such assets might often include founder shares of their businesses that if unleveraged or with very low LTVs could be plugged into a VUL structure to obtain high death benefit for the next generations. This will also help ensure that the founder shares are transferred seamlessly and smoothly to the next generations because probate is bypassed, she noted.

She also referred to work they had conducted for banks to wrap clients Discretionary Portfolio Mandates within a VUL. This idea is gaining so much traction recently because the benefits are multi-fold, she said, not just for the client, but also for the banks. The clients can use the DPM to fund the premium of the policy, and the bank retains the existing AUM, and even become stickier as the client is then less inclined to transfer the assets out to another bank.

Moreover, they added that the wealth accumulation is still provided, but the clients also obtain the two additional pieces easy wealth distribution with the nomination of beneficiaries, and also wealth protection, thanks to cover given by Swiss Life.

They closed the presentation by reiterating the value of engaging clients in these discussions and reminded delegates of the close relationships Swiss Life has long enjoyed with major financial intermediaries across the globe.

See the original post here:

Swiss Life on Capturing Untapped HNW Sales Opportunities in Asia -Asian Wealth Management and Asian Private Banking - Hubbis

More than two years into the pandemic, SARS-CoV-2, the virus that causes COVID-19, continues to challenge us. Its ability to rapidly mutate has seen the evolution of increasingly infectious variants that are getting better at hiding from our immune response.

Vaccines are a huge achievement of modern-day science and have played a crucial role in reducing the very worst impacts of COVID. But are the vaccines we currently have able to deal with the newest COVID variants?

The current COVID vaccines are all based on the genetic building blocks, or the DNA sequence, of the original ancestral strain of SARS-CoV-2. The majority of these vaccines target the spike protein the part of the virus that attaches to our cells to gain entry.

The vaccines work by enabling our immune cells to mount a targeted response to the spike protein, including generating antibodies known as neutralising antibodies. These stop viruses getting into our cells, and help other immune cells find and destroy any viral intruders.

But SARS-CoV-2 is a slippery customer and has been mutating with notable changes to the spike protein. That means those vaccine-induced neutralising antibodies are less effective than they once were.

The idea to vaccinate against variants rather than the ancestral strain is gaining traction. This is not a new concept in vaccine development. Our annual flu shots, for example, target circulating variants.

One approach is to create whats called a bivalent vaccine that targets the spike protein from omicron (BA.1) as well as the ancestral strain. Moderna is currently testing this option in combined phase 2 and 3 human trials. Data yet to be peer-reviewed suggests this results in around a two-fold increase in neutralising antibodies against BA.1, compared with the original COVID vaccines.

Other Moderna trials are looking at different bivalent combinations, including vaccines that target the ancestral and beta strains, which look promising.

Pfizer has also released trial data on its booster candidate specifically tailored against BA.1. The company says this reformulation induced an immune response to BA.1 superior to that produced by its original COVID vaccine.

So should we be investing in these new vaccine candidates? The US Food and Drug Administration seems to think so, having recently approved the use of these omicron-specific shots later this year.

However, investing in and rolling out new vaccines is not cheap, and there are important questions we need to address. As we know, SARS-CoV-2 is ever mutating and changing. It was less than a year ago that the delta strain dominated around the world, and before that we had alpha and beta. So are omicron variants the right ones to be targeting? Will they still be dominant a year from now? We simply dont know.

Even with omicron strains there is variation. The BA.1 variant that these new vaccine candidates target has recently been outcompeted by BA.4 and BA.5. The BA.4 and BA.5 variants are even more resistant to neutralising antibodies, typically three- or four-fold, than BA.1. So the question is, if omicron pervades, would these omicron BA.1 vaccines work better against BA.4 and BA.5 than the original vaccines? Data still to be peer reviewed suggests the bivalent vaccines may be a little better than the original vaccines.

However, omicron may be a poor vaccine candidate as recent data shows that omicron infection doesnt produce robust immunity and is characterised by low levels of neutralising antibodies, which need to be higher and more persistent to prevent rapid reinfection. This could go a long way to explaining why so many of us are catching COVID multiple times. If we see the same thing with our vaccine-induced immunity to omicron, omicron-specific vaccines may not be a worthwhile investment.

None of this means we should stop looking for long-term protective vaccines. But perhaps theres scope to focus on different strategies. Two exciting avenues are emerging.

The first is vaccines that target other parts of the viral structure that are more stable, or vaccines that target multiple parts of the virus. This might not result in a vaccine that can fully prevent infection, but may be more durable than the current vaccines.

Another avenue involves capitalising on the ability of neutralising antibodies in the nose and throat to target SARS-CoV-2 at its point of entry. These antibodies create a barrier that stops the virus getting into the body, so a vaccine that generates neutralising antibodies in the nose and throat could stop the virus in its tracks. Studies trialling nasal vaccines look promising, although these are still at early stages.

Where does this leave us now? An ideal vaccine candidate would elicit long-lived neutralising antibodies and give us life-long immunity. Instead, weve learnt that for COVID, our immune system needs boosters to top up those neutralising antibodies and bolster the numbers of memory cells that support immunity.

The last UK-wide booster campaign was in December 2021. Studies had shown that COVID vaccination followed by infection lead to months of immunity, but this was before omicron, which we now know doesnt produce robust immunity. Against omicron, many of us will have minimal neutralising antibodies left.

With the high likelihood of another variant in the autumn, alongside fears of a bad flu season, it would seem prudent to embark on an autumn booster campaign with much wider coverage than the spring campaign. This means not just targeting over 65s and others at higher risk as is currently planned, but extending eligibility to younger age groups.

Crucially we must reach those who are not fully vaccinated, so any campaign should include targeted community education. This should also happen alongside other mitigation strategies like mask-wearing to keep us safe and allow us to live with COVID.

Sheena Cruickshank, Professor in Biomedical Sciences, University of Manchester

This article is republished from The Conversation under a Creative Commons license. Read the original article.

Sheena Cruickshank does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.

University of Manchester provides funding as a member of The Conversation UK.

More here:

COVID vaccines: our current shots could soon be updated to target new variants an immunology expert explains - Gavi, the Vaccine Alliance