Abstract: A method of immunizing against COVID-19 by administering a recombinant SARS-CoV2 protein-based vaccine, developed by either embedding the epitopes/domains, or chemically attaching, to an already established vaccine candidate, e.g., a detoxified recombinant tetanus neurotoxin (DrTeNT). The developed vaccine will have three novel contributions compared to the present vaccine technology: a) providing a novel and very effective vaccine platform; b) priming with DrTeNT will prepare the host immune system for better response; and c) oral delivery of the vaccine candidate with a group of neurotoxin binding proteins (NAPs) from Clostridium sp. A Detoxified recombinant tetanus neurotoxin (DrTeNT) is prepared by mutation of the active site amino acid residues is an effective vaccine candidate, and is used for embedding epitopes of SARS-CoV-2 virus protein for vaccination against Covid-19. DrTeNT is a risk-free vaccine, free of formalin or any other chemical adjuvants.

Abstract: Methods of making the M or L complex of the botulinum neurotoxin E with its associated neurotoxin binding protein(s) (NBP), and methods of using to treat pain and wrinkles by injecting locally. Methods of making and isolating the L and M complex comprise a multi-step process of: providing a bacterial cultured media comprising the complex of botulinum neurotoxin E and neurotoxin binding proteins; centrifuging and pelletizing the cultured media; stirring the pelletized culture at 0 to 10° C. over a period of 4 to 24 hours; centrifuging the stirred solution to obtain a supernatant; precipitating the supernatant and filtering to obtain the precipitate; and dissolving the precipitate, centrifuging and filtering to obtain a solution comprising M complex and/or L complex of botulinum neurotoxin E and its NBP; and passing the solution through a functionalized sephadex ion exchange column to isolate the complex.

Abstract: The present invention is directed to a composition, mammalian cell and vector, and a method for the production of, and method of treatment with, a recombinant protein vaccine in a mammalian cell line. The methods and compositions are particularly useful for generating the stable expression of a recombinant protein vaccine of interest. The invention is particularly useful for the production of vaccines to aid in protection against viral pathogens for vertebrates, in particular mammalians, especially humans. The mammalian cell for producing a protein of interest comprises: a plasmid encoded with a nucleotide sequence encoding one or more epitopes or subunits of the SARS-CoV-2 that are embedded in the nucleotide sequence encoding a detoxified recombinant tetanus toxin (DrTeNT).

Abstract: The present invention describes a second-generation tetanus toxoid vaccine and a process for the preparation thereof, comprising the steps of: inducing an E. coli culture OD600=0.5 by adding 0.2 mM IPTG; growing the culture at 14-16° C. for 14 to 20 hours; suspending the culture in 25 mM phosphate buffer containing 200 mM sodium chloride; adding 1% of triton-X-100 to the phosphate buffer, and adding the buffer to the culture; sonicating the culture for a period of 3 minutes (at 5 sec on/off pulse) at 4° C. on cold beads; centrifuging the culture for 60 to 90 minutes; collecting and purifying a supernatant using Ni-NTA affinity column with an eluant; and combining the supernatant into a pool with contaminated bands and concentrating using Centriprep-30 centrifuge filters (30 kDa pores).

Abstract: A pharmaceutical composition, method of making and treating, comprising one or more proteins of Clostridium botulinum in a nano-emulsion for topical delivery to treat primarily skin disorders. In an embodiment, the nano-emuslisons are encapsulated microspheres and nanospheres comprising: propylene glycol, phenoxyethanol, sodium hyaluronate, caprylic/capric triglyceride, hydrogenated castor oil, span-80, and saponin, with water. A method of making the nanoemulsions, comprises: (1) preparing a solution A by mixing sodium hyaluronate, propylene glycol, Tween-80 and saponin in water by continuous stirring; (2) preparing a solution B by mixing phenoxy ethanol and carylic acid, or capric triglyceride, together; (3) mixing B into A by continuous stirring for 15 minutes to form solution C; (4) mixing Botulinum toxin and 10 mM Sodium Phosphate buffer to a pH of 7.1, and adding to solution C; and (5) stirring solution C at room temperature for 15-20 minutes.

Abstract: A recombinant SARS-CoV2 protein-based vaccine, and method of immunizing, is developed by either embedding the epitopes/domains, or chemically attaching, to an already established vaccine candidate, such as a detoxified recombinant tetanus neurotoxin (DrTeNT), to develop a novel vaccine to immunize against SARS-CoV2. The developed vaccine will have three novel contributions compared to the present vaccine technology; a) providing a novel and very effective vaccine platform; b) priming with DrTeNT will prepare the host immune system for better response; and c) oral delivery of the vaccine candidate with a group of neurotoxin binding proteins (NAPs) from Clostridium sp. A Detoxified recombinant tetanus neurotoxin (DrTeNT) is prepared by mutation of the active site amino acid residues is an effective vaccine candidate, and is to be used for embedding epitopes of SARS-CoV-2 virus protein for vaccination against Covid-19. DrTeNT is a risk-free vaccine, free of formalin or any other chemical adjuvants.

Abstract: The present invention comprises of a vaccine technology to produce one or more novel vaccine compositions, method of making, and administering, for protecting against at least two of the four serotypes of the dengue virus. The vaccine technology is based on four important ideas: a) using a backbone for a vaccine candidate comprising detoxified tetanus neurotoxin—DrTeNT; b) selecting epitopes that can activate both B-cells and T-cells in a patient to whom the vaccine is administered to provide long term immunity; c) immunizing against all the four serotypes of dengue; and d) an oral/sublingual/buccal/nasal delivery platform and formulation.

Abstract: The present invention describes a second-generation tetanus toxoid vaccine and a process for the preparation thereof, comprising the steps of: inducing an E. Coli culture OD 600=0.5 by adding 0.2 mM IPTG; growing the culture at 14-16° C. for 14 to 20 hours; suspending the culture in 25 mM phosphate buffer containing 200 mM sodium chloride; adding 1% of triton-X-100 to the phosphate buffer, and adding the buffer to the culture; sonicating the culture for a period of 3 minutes (at 5 sec on/off pulse) at 4° C. on cold beads; centrifuging the culture for 60 to 90 minutes; collecting and purifying a supernatant using Ni-NTA affinity column with an eluant; and combining the supernatant into a pool with contaminated bands and concentrating using Centriprep-30 centrifuge filters (30 kDa pores).

Abstract: Methods of making the M or L complex of the botulinum neurotoxin E with its associated neurotoxin binding protein(s) (NBP), and methods of using to treat pain and wrinkles by injecting locally. Methods of making and isolating the L and M complex comprise a multi-step process of: providing a bacterial cultured media comprising the complex of botulinum neurotoxin E and neurotoxin binding proteins; centrifuging and pelletizing the cultured media; stirring the pelletized culture at 0 to 10° C. over a period of 4 to 24 hours; centrifuging the stirred solution to obtain a supernatant; precipitating the supernatant and filtering to obtain the precipitate; and dissolving the precipitate, centrifuging and filtering to obtain a solution comprising M complex and/or L complex of botulinum neurotoxin E and its NBP; and passing the solution through a functionalized sephadex ion exchange column to isolate the complex.

Abstract: Techniques for continuous lock-minimal checkpointing and recovery with a distributed log-based datastore are described. A continuous, fault-tolerant checkpoint process is run on a node in a cluster in a compute-optimized or memory-optimized manner, thereby checkpointing the in-memory replica state of the node to a durable checkpoint datastore. A node can partially restore its replica state by obtaining checkpoint data, which includes an identifier of a low-water mark in a journal shard. The node can attach to the journal shard using the low-mater mark as the point of attachment, enabling the node to finalize the restoration of the replica state to be current.

Abstract: The present invention describes a second-generation tetanus toxoid vaccine and a process for the preparation thereof, comprising the steps of: inducing an E. Coli culture OD 600=0.5 by adding 0.2 mM IPTG; growing the culture at 14-16° C. for 14 to 20 hours; suspending the culture in 25 mM phosphate buffer containing 200 mM sodium chloride; adding 1% of triton-X-100 to the phosphate buffer, and adding the buffer to the culture; sonicating the culture for a period of 3 minutes (at 5 sec on/off pulse) at 4° C. on cold beads; centrifuging the culture for 60 to 90 minutes; collecting and purifying a supernatant using Ni-NTA affinity column with an eluant; and combining the supernatant into a pool with contaminated bands and concentrating using Centriprep-30 centrifuge filters (30 kDa pores).

Abstract: Compositions comprising the L complex or the M complex of the botulinum neurotoxin E with its associated neurotoxin binding protein(s) (NBP), methods of making, and methods of use to treat pain and wrinkles by injecting locally. Methods of making and isolating the L and M complex comprise a multi-step process of: providing a bacterial cultured media comprising the complex of botulinum neurotoxin E and neurotoxin binding proteins; centrifuging and pelletizing the cultured media; stirring the pelletized culture at 0 to 10° C. over a period of 4 to 24 hours; centrifuging the stirred solution to obtain a supernatant; precipitating the supernatant and filtering to obtain the precipitate; and dissolving the precipitate, centrifuging and filtering to obtain a solution comprising M complex and/or L complex of botulinum neurotoxin E and its NBP; and passing the solution through a functionalized sephadex ion exchange column to isolate the complex.

Abstract: Techniques for multi-stream transactional event processing under ACID semantics in a distributed log-based append-only datastore are described. A transaction coordinator writes events that are part of a transaction to a transaction buffer, where the events can be made visible to clients involved in the transaction while other clients are not aware. Upon committing the transaction, an optimistic concurrency control based technique is utilized to attempt to obtain locks on all events involved in the transaction across one or multiple shards by one or multiple designated writer nodes. When all involved writer nodes indicate that they are able to commit their events, the transaction can be committed.

Abstract: In one aspect, an example methodology implementing the disclosed techniques includes, by an order prioritization service, receiving information regarding orders that need to be fulfilled and determining, for each one of the orders, one or more relevant features from the information regarding the order, the one or more relevant features influencing prediction of an order priority. The method also includes, by the order prioritization service, predicting, using a machine learning (ML) model, a priority score for each one of the orders based on the determined one or more relevant features, and ranking the orders based on their respective priority scores.

Abstract: The present invention describes a neurotoxin associated protein from botulinum neurotoxin complex used as an oral or nasal delivery system for a vaccine. The vaccine is selected from tetanus, diphtheria and pertussis alone or in combination. Further the oral or nasal delivery of tetanus vaccine in combination with other drug molecules.

Abstract: A recombinant SARS-CoV2 protein-based vaccine, and method of immunizing, is developed by either embedding the epitopes/domains, or chemically attaching, to an already established vaccine candidate, such as a detoxified recombinant tetanus neurotoxin (DrTeNT), to develop a novel vaccine to immunize against SARS-CoV2. The developed vaccine will have three novel contributions compared to the present vaccine technology; a) providing a novel and very effective vaccine platform; b) priming with DrTeNT will prepare the host immune system for better response; and c) oral delivery of the vaccine candidate with a group of neurotoxin binding proteins (NAPs) from Clostridium sp. A Detoxified recombinant tetanus neurotoxin (DrTeNT) is prepared by mutation of the active site amino acid residues is an effective vaccine candidate, and is to be used for embedding epitopes of SARS-CoV-2 virus protein for vaccination against Covid-19. DrTeNT is a risk-free vaccine, free of formalin or any other chemical adjuvants.

Abstract: An example methodology implementing the disclosed techniques includes receiving a parts configuration specified for a product and generating a first feature vector that represents features from the product. The method also includes predicting, using a trained quote-time issue prediction module, whether the parts configuration specified for the product will or will not result in issues based on the first feature vector and, responsive to a prediction that the parts configuration specified for the product will not result in issues, accepting an order for the product. The method may further include receiving manufacturing details selected for the product, generating a second feature vector that represents features from the product and the selected manufacturing details, and predicting, using a trained manufacture-time issue prediction module, whether producing the product in accordance with the selected manufacturing details will or will not result in issues based on the second feature vector.

Abstract: In one aspect, an example methodology implementing the disclosed techniques includes receiving a corpus of historical order fulfillment data regarding a plurality of completed orders for one or more products, the historical order fulfillment data including an actual delivery time for each product in a completed order, and identifying, from the corpus of historical order fulfillment data, a plurality of features for a product, the plurality of features correlated with an actual delivery time for the product. The method also includes generating a training dataset using the identified plurality of features, the training dataset including a plurality of training samples, each training sample of the plurality of training samples corresponding to a product and including one or more identified features and the actual delivery time for the product. The method may include training the delivery time prediction module using the plurality of training samples.

Abstract: The present invention provides a method for detecting and assaying Clostridium neurotoxins and identification of serotypes of botulinum neurotoxins in various food matrices and clinical samples. This method is also used for detection of BoNT inside the neuronal and epithelial cells. The method comprises detecting and assaying the presence of a Clostridium neurotoxin in a sample by: exposing the sample containing a Clostridium neurotoxin to a sample comprising a novel SNAMPXIN/SNAMP universal recombinant substrate fusion protein capable of producing a detectable FRET, following cleavage; detecting and assaying the presence of the Clostridium neurotoxin by measuring a change in the energy transfer or the luminescence signal; and detecting and assaying an electrophoretic mobility pattern of one or more cleaved protein bands or a degraded protein, using a high throughput automated system to identify the different serotypes of the Clostridium neurotoxin.

Abstract: Compositions comprising the L complex or the M complex of the botulinum neurotoxin E with its associated neurotoxin binding protein(s) (NBP), methods of making, and methods of use to treat pain and wrinkles by injecting locally. Methods of making and isolating the L and M complex comprise a multi-step process of: providing a bacterial cultured media comprising the complex of botulinum neurotoxin E and neurotoxin binding proteins; centrifuging and pelletizing the cultured media; stirring the pelletized culture at 0 to 10° C. over a period of 4 to 24 hours; centrifuging the stirred solution to obtain a supernatant; precipitating the supernatant and filtering to obtain the precipitate; and dissolving the precipitate, centrifuging and filtering to obtain a solution comprising M complex and/or L complex of botulinum neurotoxin E and its NBP; and passing the solution through a functionalized sephadex ion exchange column to isolate the complex.