The invention relates to a chimeric antigen receptor comprising an antigen-binding domain, wherein said antigen-binding domain comprises a single chain variable fragment; an ectodomain spacer; a synthetic GLUT4 transmembrane peptide composed of 19 to 23 amino acids; and an endodomain. Said chimeric antigen receptor is remarkable in that the synthetic GLUT4 transmembrane peptide yields increased recruitment of signaling partners and tumor clearing properties.
Disclosed herein are lipid nanoparticles comprising one or more neutral lipid, one or more sterol, one or more cationic lipid, one or more ionizable lipid, and one or more PEG- modified lipid; in particular, the lipid nanoparticles comprising 1,2-dioleoyl-sn-glycero- 3-phosphocholine (DOPC), 1,2-Dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE), 1,2-Dioleoyl-3-trimethylammoniumpropane (DOTAP), 6-((2-hexyldecanoyl)oxy)-N-(6- ((2-hexyldecanoyl)oxy)hexyl)-N-(4-hydroxybutyl)hexan-1 aminium (ALC-0315), and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[maleimide(polyethylene glycol)- 2000] (DSPE-PEG2000); compositions comprising such lipid nanoparticles, and methods of using such lipid nanoparticles and compositions.
A61K 31/685 - Diesters of a phosphorus acid with two hydroxy compounds, e.g. phosphatidylinositols one of the hydroxy compounds having nitrogen atoms, e.g. phosphatidylserine, lecithin
A61K 31/7105 - Natural ribonucleic acids, i.e. containing only riboses attached to adenine, guanine, cytosine or uracil and having 3'-5' phosphodiester links
A61K 47/54 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound
3.
METHODS FOR THE IDENTIFICATION AND CHARACTERIZATION OF DOUBLE-STRAND BREAK SITES AND COMPOSITIONS AND USES THEREOF
Methods and compositions are provided for the identification, detection, characterization, and/or utilization of double strand breaks in a target polynucleotide; the identification, detection, characterization, and/or utilization of cutting sites for double-strand-break-inducing agents; and the identification, detection, characterization, and/or utilization of double-strand-break-inducing agents.
The present invention concerns a method comprising co-encapsulating a microcapsule and a particle in a droplet, the microcapsule comprising a semi-permeable shell and a core, wherein the core comprises a nucleic acid for processing, and wherein the particle comprises a reagent for use in the processing of the nucleic acid.
The present invention concerns a method of performing one or more reactions on a biological entity, the method comprising: (i) isolating the biological entity in a microcapsule comprising a core and a semi-permeable shell; and (ii) performing the one or more reactions on the biological entity in the microcapsule.
The present invention concerns new subtype V-U1 CRISPR-Cas effector proteins. The invention further relates to the methods of repressing or interfering with the expression of target gene sequences and base editing in cells or in any nucleic acid in vitro.
A method is disclosed for chemo-enzymatic production of the functionally active stereoisomer of S-adenosyl-L-methionine analogs with extended transferable moieties of formula (I) and (II) from corresponding alkylbromides and S-adenosyl-L-homocysteine.
C12P 19/40 - Nucleosides having a condensed ring system containing a six-membered ring having two nitrogen atoms in the same ring, e.g. purine nucleosides
C12N 15/11 - DNA or RNA fragmentsModified forms thereof
C12P 19/34 - Polynucleotides, e.g. nucleic acids, oligoribonucleotides
C07H 19/167 - Purine radicals with ribosyl as the saccharide radical
9.
TARGETED COVALENT INHIBITORS FOR CARBONIC ANHYDRASES
This invention teaches a class of fluorinated benzenesulfonamides of general structure I, as shown:
This invention teaches a class of fluorinated benzenesulfonamides of general structure I, as shown:
This invention teaches a class of fluorinated benzenesulfonamides of general structure I, as shown:
which are useful for binding and inhibiting carbonic anhydrases irreversibly. The compounds taught can be used in pharmaceutical compositions in effective amounts to treat diseases/disorders responsive to the inhibition of human carbonic anhydrases.
C07C 317/32 - SulfonesSulfoxides having sulfone or sulfoxide groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton with sulfone or sulfoxide groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton
10.
EX VIVO CELLULAR MODEL SYSTEM COMPRISING HETEROGENOUS CELLS FROM HUMAN LUNG TUMOR FOR THE EVALUATION OF DRUG CYTOTOXICITY IN VITRO AND METHOD THEREOF
The invention is a model of research and methodology to explore the treatment options for a particular case of lung cancer as an adjuvant therapy after surgical removal of a lung tumor. In practice, the excised/removed tumor is usually examined in the pathology laboratory for revision of the diagnosis, but no functional testing is performed for its sensitivity to subsequent adjuvant 5 therapy. In addition, the tumor is disposed of as unnecessary waste. Our proposal is that the tumor remains should be harvested for cellular studies and, using the model and methodology developed and described herein, preliminary answers can be obtained within 2-3 weeks, predicting which chemotherapeutic agents are likely to have a stronger effect and which therapy is likely to be ineffective for an individual lung cancer patient.
Rapid, sensitive and cost-efficient detection and characterization method for in vitro double strand breaks produced by CRISPR-Cas9 nucleases from human genomic DNA samples.
The present invention concerns a method for cleaving polynucleotides with an effector complex comprising an RNA and a protein comprising a TnpB protein, and related methods and products.
The present invention concerns a method for sequentially attaching a plurality of oligonucleotides to nucleic acids to produce barcoded nucleic acids, wherein the nucleic acids are obtained from a plurality of cells, wherein the plurality of cells are in a plurality of microcapsules, each microcapsule comprising a semi-permeable shell and a core.
This invention relates to methods and systems for isolation of species in semi-permeable capsules and processing of encapsulated species through series of steps and/or reactions. To produce capsules, first aqueous two-phase system (ATPS) droplets are generated using microfluidics system. Then the hydrogel shell layer is hardened by inducing polymerization. As exemplified in this invention to achieve concentric ATPS droplet formation density-matched PEGDA and Dextran polymer solutions can be used. Once a capsule is formed, its composition can be changed by adding new reagents or replacing out old ones (e.g. by resuspending capsules in desired aqueous solution). The hydrogel shell of semi-permeable capsules can be dissolved at selected step during multi-step procedures to release the encapsulated species. This invention exemplifies isolation of individual cells within capsules and using the encapsulated cells for genotypic and phenotypic analysis. This invention also exemplifies use of capsules in multi-step procedures to perform complex biological reactions.
The present invention relates to amphiphiles and specifically the amphiphiles that can be used as cell lysis reagents. The invention reveals the amphiphiles as well as their combinations for efficiently lysing the mammalian cells under relatively mild conditions that are compatible with a reverse transcription and polymerase chain reaction. The invention reveals the use of mixture of amphiphiles to improve the cell lysis and obtain increased yields of copy DNA during the reverse transcription reaction. The invention also provides a method for increasing the diversity of gene and transcript capture during single-cell RNA-sequencing using droplet microfluidics.
This invention relates to a field of novel multi-headed compounds capable of binding and inhibiting the catalytic activity of human carbonic anhydrases for diagnostic, visualization, and treatment purposes. A series of compounds containing two or more of carbonic anhydrase inhibitors are linked together via short or long linker molecular moieties. Such dimeric or multimeric inhibitors are designed in such a way that one inhibitor molecule is able to reach several CA IX molecules on the surface of cancer cells. Such compounds are expected to have a significantly more powerful therapeutic effect and may be used for various strategies of specific compound deliveries to the desired site.
A61K 47/54 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound
A61K 47/60 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
This invention teaches a class of fluorinated benzensulfonamides of general structure I, as shown:
which are useful for inhibiting protein amyloid aggregation. The compounds taught can be used in pharmaceutical compositions in effective amounts to treat illnesses that result from protein amyloid aggregation.
A61K 31/196 - Carboxylic acids, e.g. valproic acid having an amino group the amino group being directly attached to a ring, e.g. anthranilic acid, mefenamic acid, diclofenac, chlorambucil
A61K 31/195 - Carboxylic acids, e.g. valproic acid having an amino group
A61K 31/63 - Compounds containing para-N-benzene- sulfonyl-N-groups, e.g. sulfanilamide, p-nitrobenzenesulfonohydrazide
A61P 25/28 - Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
19.
System for visual data analysis of ultrasound examinations with and without a contrast medium, for early automated diagnostics of pancreatic pathologies
We present a system and method for analysis of image and data of ultrasound and ultrasound with contrast medium of human pancreatic tissues to automatically diagnose acute pancreatitis of the pancreas and identify pancreatic non-viable tissues at an early stage. The system consists of a diagnostic ultrasound system with specialized software for contrast studies (ultrasound) for in vivo ultrasound examinations of human internal organs, recording reflected ultrasound signals from pancreatic tissues (without contrast material and when contrast material is injected) and an image and data processing algorithm with artificial intelligence (neural network) elements providing a diagnostic estimate of a recommendatory nature.
Isolation or in vitro assembly of the Cas9-crRNA complex of the Streptococcus thermophilus CRISPR3/Cas system and use for cleavage of DNA bearing a nucleotide sequence complementary to the crRNA and a proto-spacer adjacent motif. Methods for site-specific modification of a target DNA molecule in vitro or in vivo using an RNA-guided DNA endonuclease comprising RNA sequences and at least one of an RuvC active site motif and an HNH active site motif; for conversion of Cas9 polypeptide into a nickase cleaving one strand of double-stranded DNA by inactivating one of the active sites (RuvC or HNH) in the polypeptide by at least one point mutation; for assembly of active polypeptide-polyribonucleotides complex in vivo or in vitro; and for re-programming a Cas9-crRNA complex specificity in vitro and using a cassette containing a single repeat-spacer-repeat unit.
The present disclosure provides in one aspect a microcapsule comprising: (a) a core comprising a polyhydroxy compound and/or an antichaotropic agent; and (b) a semi-permeable shell surrounding the core; wherein the semi-permeable shell comprises a gel formed from a polyampholyte, wherein the polyampholyte in the gel is covalently cross-linked. The present disclosure provides further aspects relating to a method of making a microcapsule, methods of using the microcapsule and kits for making a microcapsule.
The present invention concerns a method of performing one or more reactions on a biological entity, the method comprising: (i) isolating the biological entity in a microcapsule comprising a core and a semi-permeable shell; and (ii) performing the one or more reactions on the biological entity in the microcapsule.
The present invention concerns a method for sequentially attaching a plurality of oligonucleotides to nucleic acids to produce barcoded nucleic acids, wherein the nucleic acids are obtained from a plurality of cells, wherein the plurality of cells are in a plurality of microcapsules, each microcapsule comprising a semi-permeable shell and a core.
The present invention concerns a method comprising co-encapsulating a microcapsule and a particle in a droplet, the microcapsule comprising a semi-permeable shell and a core, wherein the core comprises a nucleic acid for processing, and wherein the particle comprises a reagent for use in the processing of the nucleic acid.
This invention relates to a method that covalently modifies unmodified and hydroxymethylated genomic sites in fetal specific genetic material present in maternal blood DNA samples and produce the adjacent genomic regions for detecting fetal aneuploidies and fetal gender using quantitative real time PCR or sequencing. A large panel of differently labeled sites and regions between maternal and fetal genetic material has been identified and they validity for diagnostic purposes of fetal trisomy of chromosome 21 has been demonstrated.
Isolation or in vitro assembly of the Cas9-crRNA complex of the Streptococcus thermophilus CRISPR3/Cas system and use for cleavage of DNA bearing a nucleotide sequence complementary to the crRNA and a proto-spacer adjacent motif. Methods for site-specific modification of a target DNA molecule using an RNA-guided DNA endonuclease comprising at least one RNA sequence and at least one of an RuvC active site motif and an HNH active site motif; for conversion of Cas9 polypeptide into a nickase cleaving one strand of double-stranded DNA by inactivating one of the active sites (RuvC or HNH) in the polypeptide by at least one point mutation; for assembly of active polypeptide-polyribonucleotides complex in vivo or in vitro; and for re-programming a Cas9-crRNA complex specificity in vitro or using a cassette containing a single repeat-spacer-repeat unit.
The Brigham and Women's Hospital, Inc., Boston, MA; (USA)
President and Fellows of Harvard College (USA)
Vilnius University (Lithuania)
Inventor
Italiano, Joseph
Mazutis, Linas
Thon, Jonathan N.
Weitz, David A.
Abstract
A system and method are provided for harvesting target biological substances. The system includes a substrate and a first and second channel formed in the substrate. The channels longitudinally extending substantially parallel to each other. A series of gaps extend from the first channel to the second channel to create a fluid communication path passing between a series of columns with the columns being longitudinally separated by a predetermined separation distance. The system also includes a first source configured to selectively introduce into the first channel a first biological composition at a first channel flow rate and a second source configured to selectively introduce into the second channel a second biological composition at a second channel flow rate. The sources are configured to create a differential between the first and second channel flow rates to generate physiological shear rates along the second channel that are bounded within a predetermined range.
The present invention concerns a method for cleaving polynucleotides with an effector complex comprising an RNA and a protein comprising a TnpB protein, and related methods and products.
The invention generally relates to the field of protein sequences and of generation of functional protein sequences. More particularly, the invention concerns a method for generating functional protein sequences with generative adversarial networks. The described method for functional sequence generation comprises plurality of steps, each of which is crucial to ensure the high percentage of functional sequences in the final sequence set: selecting a plurality of existing protein sequences to define the approximate sequence space for the later generated synthetic sequences, processing the selected protein sequences, approximating the unknown true distribution of amino acids of the pre-processed sequences using a variation of generative adversarial networks, obtaining protein sequences from the approximated distribution, processing of the obtained protein sequences. The described method provides a resource (e.g. time, cost) efficient way of producing synthetic protein sequences which have a high probability of being functional experimentally.
The present invention—PROMESYS—relates to methods and tools for diagnosis and prognosis of prostate cancer, patient monitoring/follow-up and prediction of response to treatment of patients with confirmed diagnosis of prostate cancer. The methods conducted in vitro comprise the steps of providing a tissue and/or a body fluid sample, obtained from an individual, and determining DNA methylation status and/or level of one or more genes selected from the group consisting of PRKCB, ADAMTS12, NAALAD2, FILIP1L, ZMIZ1 and KCTD8 in a sample. Additionally, methylation status and/or level of CCDC181, MT1E, APC and/or RASSF1 can be included in the biomarker panel for improved performance. Furthermore, the present invention refers to kits and oligonucleotides for use in such a method.
C12Q 1/6886 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
31.
CLEAR CELL RENAL CELL CARCINOMA BIOMARKERS AND USES THEREFOR
The present invention refer to biomarkers, methods and tools for the detection, diagnosis, prognosis and monitoring/active surveillance of the individuals having clear cell renal cell carcinoma or small renal masses. The methods consist of obtainment of biological sample (tissues or urine) and determination of the DNA methylation status and/or methylation level of at least one of biomarkers, including ZNF677, FBN2, PCDH8, TFAP2B, TAC1, FLRT2, SFRP1, ADAMTS19, BMP7 and SIM1. Moreover the described invention provides the kits, primers and probes for use in such a method.
C12Q 1/6886 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
32.
CARBONIC ANHYDRASE INHIBITORS SYNTHESIZED ON INTERCONNECTING LINKER CHAINS
This invention relates to a field of novel multi-headed compounds capable of binding and inhibiting the catalytic activity of human carbonic anhydrases for diagnostic, visualization, and treatment purposes. A series of compounds containing two or more of carbonic anhydrase inhibitors are linked together via short or long linker molecular moieties. Such dimeric or multimeric inhibitors are designed in such a way that one inhibitor molecule is able to reach several CA IX molecules on the surface of cancer cells. Such compounds are expected to have a significantly more powerful therapeutic effect and may be used for various strategies of specific compound deliveries to the desired site.
C07C 311/29 - Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound oxygen atoms having the sulfur atom of at least one of the sulfonamide groups bound to a carbon atom of a six-membered aromatic ring
We present a new method to automatically sample the tumour/stroma interface zone (IZ) from microscopy image analysis data. It first delineates the tumour edge using a set of explicit rules in grid-subsampled tissue areas; then the IZ of controlled width is sampled and ranked by the distance from the edge to compute TIL density profiles across the IZ. From this data, a set of novel Immunogradient indicators are computed to reflect TIL “gravitation” towards the tumour. We applied the method on CD8 immunohistochemistry images of surgically excised breast and colorectal cancers to predict overall patient survival. In both patient cohorts, we found strong and independent prognostic value of the Immunogradient indicators, outperforming methods currently available. We conclude that data-driven, automated, human operator-independent IZ sampling enables precise spatial immune response measurement in the tumour/host interaction frontline for prediction of disease and therapy outcomes.
A SYSTEM FOR VISUAL DATA ANALYSIS OF ULTRASOUND EXAMINATIONS WITH AND WITHOUT A CONTRAST MEDIUM, FOR EARLY AUTOMATED DIAGNOSTICS OF PANCREATIC PATHOLOGIES
in vivoin vivo ultrasound examinations of human internal organs, recording reflected ultrasound signals from pancreatic tissues (without contrast material and when contrast material is injected) and an image and data processing algorithm with artificial intelligence (neural network) elements providing a diagnostic estimate of a recommendatory nature.
The method of remotely interfering with electronic equipment of a target having electronic equipment, comprising generating of more than one signal, and emitting it through one or more antennas. One or more antennas emit signals of different frequencies that reach the target unchanged and excite non-linear frequency mixing processes in the target electronic components that generate at least one signal whose frequency differs from the frequencies of the signals emitted from one or more antennas and corresponds to the operating frequencies of the target electronic equipment.
This invention describes a method for early diagnostics of severe pancreatitis using cell membrane damage detection mechanisms. The method involves a non-invasive testing of human urine or other body fluids samples of patients that are suspected to be affected by acute pancreatitis. The invention is based on heat shock protein HSP-70, 90, 60, and 27 role of action in disease progression.
The present invention generally relates to microfluidics and labeled nucleic acids. For example, certain aspects are generally directed to systems and methods for labeling nucleic acids within microfluidic droplets. In one set of embodiments, the nucleic acids may include “barcodes” or unique sequences that can be used to distinguish nucleic acids in a droplet from those in another droplet, for instance, even after the nucleic acids are pooled together. In some cases, the unique sequences may be incorporated into individual droplets using particles and attached to nucleic acids contained within the droplets (for example, released from lysed cells). In some cases, the barcodes may be used to distinguish tens, hundreds, or even thousands of nucleic acids, e.g., arising from different cells or other sources.
The present invention relates to catalytic biomolecule characterization and microfluidics. It is used for identification of nucleic acids encoding active catalytic molecules in the plurality of nucleic acids and for gathering information about catalytic biomolecule activity. It can also be used for exploring different properties of regulating sequences that modulate expression of catalytic biomolecules by recording that information into the DNA sequence of the same catalytic biomolecule using microfluidic techniques.
This invention relates to a method that covalently modifies unmodified and hydroxymethylated genomic sites in fetal specific genetic material present in maternal blood DNA samples and produce the adjacent genomic regions for detecting fetal aneuploidies and fetal gender using quantitative real time PCR or sequencing. A large panel of differently labeled sites and regions between maternal and fetal genetic material has been identified and they validity for diagnostic purposes of fetal trisomy of chromosome 21 has been demonstrated.
C12Q 1/6827 - Hybridisation assays for detection of mutation or polymorphism
C12Q 1/6853 - Nucleic acid amplification reactions using modified primers or templates
C12Q 1/6883 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
40.
Methods for the identification and characterization of double-strand break sites and compositions and uses thereof
Methods and compositions are provided for the identification, detection, characterization, and/or utilization of double strand breaks in a target polynucleotide; the identification, detection, characterization, and/or utilization of cutting sites for double-strand-break-inducing agents; and the identification, detection, characterization, and/or utilization of double-strand-break-inducing agents.
A method of synthetizing cyclic oligoadenylates using a novel catalytic activity of a protein possessing the Palm domain, such as the Cas10 protein, and using such compounds for activation of proteins possessing the CARF doman, such as the Csm6 protein.
The invention generally relates to the field of protein sequences and of generation of functional protein sequences. More particularly, the invention concerns a method for generating functional protein sequences with generative adversarial networks. The described method for functional sequence generation comprises plurality of steps, each of which is crucial to ensure the high percentage of functional sequences in the final sequence set: selecting a plurality of existing protein sequences to define the approximate sequence space for the later generated synthetic sequences, processing the selected protein sequences, approximating the unknown true distribution of amino acids of the pre-processed sequences using a variation of generative adversarial networks, obtaining protein sequences from the approximated distribution, processing of the obtained protein sequences. The described method provides a resource (e.g. time, cost) efficient way of producing synthetic protein sequences which have a high probability of being functional experimentally.
PRKCB, ADAMTS12, NAALAD2, FILIP1L, ZMIZ1CCDC181, MT1E, APCRASSF1RASSF1 can be included in the biomarker panel for improved performance. Furthermore, the present invention refers to kits and oligonucleotides for use in such a method.
C12Q 1/6886 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
44.
Systems and methods for encapsulation and multi-step processing of biological samples
The present invention relates to methods and systems for isolation of species in semi-permeable capsules and processing of encapsulated species through series of steps and/or reactions. To produce capsules, first aqueous two-phase system (ATPS) droplets are generated using microfluidics system and then the hydrogel shell layer is hardened by inducing polymerization. As exemplified in this invention to achieve concentric ATPS droplet formation density-matched PEGDA and Dextran polymer solutions can be used. Once a capsule is formed, its composition can be changed by adding new reagents or replacing out old ones (e.g. by resuspending capsules in desired aqueous solution). The hydrogel shell of semi-permeable capsules can be dissolved at selected step during multi-step procedures in order to release the encapsulated species. The present invention exemplifies the isolation of individual cells within capsules and using the encapsulated cells for genotypic and phenotypic analysis. Finally, the present invention also exemplifies the use of capsules in multi-step procedures to perform complex biological reactions.
The present invention relates to methods and systems for isolation of species in semi-permeable capsules and processing of encapsulated species through series of steps and/or reactions. To produce capsules, first aqueous two-phase system (ATPS) droplets are generated using microfluidics system and then the hydrogel shell layer is hardened by inducing polymerization. As exemplified in this invention to achieve concentric ATPS droplet formation density-matched PEGDA and Dextran polymer solutions can be used. Once a capsule is formed, its composition can be changed by adding new reagents or replacing out old ones (e.g. by resuspending capsules in desired aqueous solution). The hydrogel shell of semi-permeable capsules can be dissolved at selected step during multi-step procedures in order to release the encapsulated species. The present invention exemplifies the isolation of individual cells within capsules and using the encapsulated cells for genotypic and phenotypic analysis. Finally, the present invention also exemplifies the use of capsules in multi-step procedures to perform complex biological reactions.
We present a new method to automatically sample the tumour/stroma interface zone (IZ) from microscopy image analysis data. It first delineates the tumour edge using a set of explicit rules in grid-subsampled tissue areas; then the IZ of controlled width is sampled and ranked by the distance from the edge to compute TIL density profiles across the IZ. From this data, a set of novel Immunogradient indicators are computed to reflect TIL "gravitation" towards the tumour. We applied the method on CD8 immunohistochemistry images of surgically excised breast and colorectal cancers to predict overall patient survival. In both patient cohorts, we found strong and independent prognostic value of the Immunogradient indicators, outperforming methods currently available. We conclude that data-driven, automated, human operator-independent IZ sampling enables precise spatial immune response measurement in the tumour/host interaction frontline for prediction of disease and therapy outcomes.
A system and method are provided for harvesting target biological substances. The system includes a substrate and a first and second channel formed in the substrate. The channels longitudinally extending substantially parallel to each other. A series of gaps extend from the first channel to the second channel to create a fluid communication path passing between a series of columns with the columns being longitudinally separated by a predetermined separation distance. The system also includes a first source configured to selectively introduce into the first channel a first biological composition at a first channel flow rate and a second source configured to selectively introduce into the second channel a second biological composition at a second channel flow rate. The sources are configured to create a differential between the first and second channel flow rates to generate physiological shear rates along the second channel that are bounded within a predetermined range.
Disclosed are W-position modified cytidine nucleotides of formula (I). Provided herein are methods of chemical synthesis of AP-modified cytidine nucleoside triphosphates and their applications as well as uses of the cytidine analogues for the synthesis of modified nucleic acids. The nucleic acid molecule includes DNA, RNA or a combination of DNA/RNA. One of many applications of modified cytidine nucleotides described herein is enzyme selection, when an enzyme of interest bears an activity of an esterase, amidase, oxidoreductase, lyase, ligase or other enzymatic activity, formula (I) wherein the substituants are as defined in the appended claims.
C07H 19/10 - Pyrimidine radicals with the saccharide radical being esterified by phosphoric or polyphosphoric acids
C12Q 1/68 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions involving nucleic acids
C07H 21/04 - Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids with deoxyribosyl as saccharide radical
C12N 15/10 - Processes for the isolation, preparation or purification of DNA or RNA
49.
Systems and methods for biomimetic fluid processing
Systems and methods generating physiologic models that can produce functional biological substances are provided. In some aspects, a system includes a substrate and a first and second channel formed therein. The channels extend longitudinally and are substantially parallel to each other. A series of apertures extend between the first channel and second channel to create a fluid communication path passing through columns separating the channels that extends further along the longitudinal dimension than other dimensions. The system also includes a first source configured to selectively introduce into the first channel a first biological composition at a first channel flow rate and a second source configured to selectively introduce into the second channel a second biological composition at a second channel flow rate, wherein the first channel flow rate and the second channel flow rate create a differential configured to generate physiological shear rates within a predetermined range in the channels.
This invention describes a method for early diagnostics of severe pancreatitis using cell membrane damage detection mechanisms. The method involves a non-invasive testing of human urine or other body fluids samples of patients that are suspected to be affected by acute pancreatitis. The invention is based on heat shock protein HSP-70, 90, 60, and 27 role of action in disease progression.
The present invention relates to catalytic biomolecule characterization and microfluidics. It is used for identification of nucleic acids encoding active catalytic molecules in the plurality of nucleic acids and for gathering information about catalytic biomolecule activity. It can also be used for exploring different properties of regulating sequences that modulate expression of catalytic biomolecules by recording that information into the DNA sequence of the same catalytic biomolecule using microfluidic techniques.
C12Q 1/34 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions involving hydrolase
C12Q 1/44 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions involving hydrolase involving esterase
C12Q 1/6806 - Preparing nucleic acids for analysis, e.g. for polymerase chain reaction [PCR] assay
C12N 15/10 - Processes for the isolation, preparation or purification of DNA or RNA
52.
METHODS FOR THE IDENTIFICATION AND CHARACTERIZATION OF DOUBLE-STRAND BREAK SITES AND COMPOSITIONS AND USES THEREOF
Methods and compositions are provided for the identification, detection, characterization, and/or utilization of double strand breaks in a target polynucleotide; the identification, detection, characterization, and/or utilization of cutting sites for double-strand-break-inducing agents; and the identification, detection, characterization, and/or utilization of double-strand-break-inducing agents.
Methods and compositions are provided for the identification, detection, characterization, and/or utilization of double strand breaks in a target polynucleotide; the identification, detection, characterization, and/or utilization of cutting sites for double-strand-break-inducing agents; and the identification, detection, characterization, and/or utilization of double-strand-break-inducing agents.
A system and method are provided for harvesting target biological substances. The system includes a substrate and a first and second channel formed in the substrate. The channels longitudinally extending substantially parallel to each other. A series of gaps extend from the first channel to the second channel to create a fluid communication path passing between a series of columns with the columns being longitudinally separated by a predetermined separation distance. The system also includes a first source configured to selectively introduce into the first channel a first biological composition at a first channel flow rate and a second source configured to selectively introduce into the second channel a second biological composition at a second channel flow rate. The sources are configured to create a differential between the first and second channel flow rates to generate physiological shear rates along the second channel that are bounded within a predetermined range.
Streptococcus thermophilus CRISPR3/Cas system and use for cleavage of DNA bearing a nucleotide sequence complementary to the crRNA and a proto-spacer adjacent motif. Methods for site-specific modification of a target DNA molecule using an RNA-guided DNA endonuclease comprising at least one RNA sequence and at least one of an RuvC active site motif and an HNH active site motif; for conversion of Cas9 polypeptide into a nickase cleaving one strand of double-stranded DNA by inactivating one of the active sites (RuvC or HNH) in the polypeptide by at least one point mutation; for assembly of active polypeptide-polyribonucleotides complex in vivo or in vitro; and for re-programming a Cas9-crRNA complex specificity in vitro or using a cassette containing a single repeat-spacer-repeat unit.
The present invention describes W-position modified cytidine nucleotides of formula (I). Provided herein are methods of chemical synthesis of ΛΡ-modified cytidine nucleoside triphosphates and their applications as well as uses of the cytidine analogues for the synthesis of modified nucleic acids. The nucleic acid molecule comprises DNA, RNA or a combination of DNA/RNA. One of many applications of modified cytidine nucleotides described herein is enzyme selection, when an enzyme of interest bears an activity of an esterase, amidase, oxidoreductase, lyase, ligase or other enzymatic activity, formula (I) wherein the substituants are as defined in the appended claims.
C07H 19/10 - Pyrimidine radicals with the saccharide radical being esterified by phosphoric or polyphosphoric acids
C07H 21/04 - Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids with deoxyribosyl as saccharide radical
C12N 15/00 - Mutation or genetic engineeringDNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purificationUse of hosts therefor
57.
System and method for synthesis of DNA particles and use thereof
Disclosed is a system and method for production of DNA particles and use thereof. The DNA particles can be produced by amplification of nucleic acid molecule(s). Alternatively, DNA particles can be prepared by condensing multiple DNA molecules. The DNA condensation into a particle is mainly triggered by pyrophosphate and positively charged cations (e.g. magnesium). DNA particles can be applied for numerous biological applications but not limited to directed evolution, proteomics, drug delivery and imaging. DNA particles can be used to synthesize proteins using in vitro transcription/translation reaction.
Purpose of the invention is to obtain distance and altitude data of an object position in 3D space by using conventional radar hardware including at least an antenna, a transmitter, a receiver and other devices and equipment required for operation of conventional radars, as well as an additional device for processing and presenting information obtained by the radar.
A method of synthetizing cyclic oligoadenylates using a novel catalytic activity of a protein possessing the Palm domain, such as the Cas10 protein, and using such compounds for activation of proteins possessing the CARF doman, such as the Csm6 protein.
C07H 21/00 - Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
The present invention generally relates to microfluidics and labeled nucleic acids. For example, certain aspects are generally directed to systems and methods for labeling nucleic acids within microfluidic droplets. In one set of embodiments, the nucleic acids may include “barcodes” or unique sequences that can be used to distinguish nucleic acids in a droplet from those in another droplet, for instance, even after the nucleic acids are pooled together. In some cases, the unique sequences may be incorporated into individual droplets using particles and attached to nucleic acids contained within the droplets (for example, released from lysed cells). In some cases, the barcodes may be used to distinguish tens, hundreds, or even thousands of nucleic acids, e.g., arising from different cells or other sources.
Provided is a method for modifying a ssRNA at the 3′ end, the method including contacting the strand with a ssRNA 2′-O-methyltransferase in the presence of a co-factor, under conditions which allow for the transfer by the ssRNA 2′-O-methyltransferase of a part of the co-factor onto the 3′ end of the ssRNA to form a modified ssRNA, wherein the ssRNA bears 2′-OH group at 3′ terminal nucleotide and wherein the part of the co-factor transferred includes a reporter group or a functional group.
Disclosed are novel compounds—benzenesulfonamides of general formulas (I) and (II)
The compounds can be used in biomedicine as active ingredients in pharmaceutical formulations, because they inhibit enzymes which participate in disease progression. Also disclosed are method of treatment using such compounds.
C07C 311/16 - Sulfonamides having sulfur atoms of sulfonamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the sulfonamide groups bound to hydrogen atoms or to an acyclic carbon atom
C07D 215/08 - Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to the ring carbon atoms with acylated ring nitrogen atom
C07D 235/08 - Radicals containing only hydrogen and carbon atoms
C07D 233/58 - Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring nitrogen atoms
C07D 209/08 - IndolesHydrogenated indoles with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to carbon atoms of the hetero ring
C07C 321/28 - Sulfides, hydropolysulfides, or polysulfides having thio groups bound to carbon atoms of six-membered aromatic rings
C07D 265/30 - 1,4-OxazinesHydrogenated 1,4-oxazines not condensed with other rings
Streptococcus thermophilus CRISPR3/Cas system and use for cleavage of DNA bearing a nucleotide sequence complementary to the crRNA and a proto-spacer adjacent motif. Methods for site-specific modification of a target DNA molecule in vitro or in vivo using an RNA-guided DNA endonuclease comprising RNA sequences and at least one of an RuvC active site motif and an HNH active site motif; for conversion of Cas9 polypeptide into a nickase cleaving one strand of double-stranded DNA by inactivating one of the active sites (RuvC or HNH) in the polypeptide by at least one point mutation; for assembly of active polypeptide-polyribonucleotides complex in vivo or in vitro; and for re-programming a Cas9-crRNA complex specificity in vitro and using a cassette containing a single repeat-spacer-repeat unit.
An antenna is made from strips of a shape-memory alloy or other resilient material acting as a spring with attached branches that constitute individual monopole antennas. In the folded state, the antenna looks like a strip roll and can be placed on a satellite. When in orbit, the antenna unfolds after the roll retention mechanism is released and orderly unfolds unrolling from a support frame or otherwise extends. The proposed design of monopole branches utilizes conductors of minimum length and achieves maximum directivity. Each monopole branch is connected to the signal receiver/transmitter by signal conduit elements. A system may include at least two such unfolding antennas thus achieving even greater operational effectiveness in regard to signal steerability, interference suppression and reduced moment of the satellite inertia. To prevent problems, additional measures are used that prevent unwinding of inner layers of the roll before the outer layer is extended.
H01Q 1/28 - Adaptation for use in or on aircraft, missiles, satellites, or balloons
H01Q 19/04 - Means for collapsing H-antennas or Yagi antennas
H01Q 21/12 - Parallel arrangements of substantially straight elongated conductive units
H01Q 3/26 - Arrangements for changing or varying the orientation or the shape of the directional pattern of the waves radiated from an antenna or antenna system varying the relative phase or relative amplitude of energisation between two or more active radiating elementsArrangements for changing or varying the orientation or the shape of the directional pattern of the waves radiated from an antenna or antenna system varying the distribution of energy across a radiating aperture
The compact lamp consists of a light source, a focusing lens, a specially shaped secondary lens with a saddle-shaped output surface, a light transmitting element, a battery holding chamber with an electrical control circuit connected to a button for control of the lamp source via a magnetic contact. Some of these elements are placed inside the lamp housing, mounted on an end of a handlebar or another suitable lighting device, and some other elements, including the battery and the magnetic control circuit, are installed inside the handlebar tube or the housing of the lighting device. The compact optical layout enables a beam, which is sharply limited in the vertical plane and sufficiently wide in the horizontal plane and is suitable for daytime running lamps, night headlamps or position lights. When at least two light sources are used in one lamp, beams of different light dispersion patterns can be electrically toggled.
The present invention generally relates to microfluidics and labeled nucleic acids. For example, certain aspects are generally directed to systems and methods for labeling nucleic acids within microfluidic droplets. In one set of embodiments, the nucleic acids may include “barcodes” or unique sequences that can be used to distinguish nucleic acids in a droplet from those in another droplet, for instance, even after the nucleic acids are pooled together. In some cases, the unique sequences may be incorporated into individual droplets using particles and attached to nucleic acids contained within the droplets (for example, released from lysed cells). In some cases, the barcodes may be used to distinguish tens, hundreds, or even thousands of nucleic acids, e.g., arising from different cells or other sources.
A system and method are provided for harvesting target biological substances. The system includes a substrate and a first and second channel formed in the substrate. The channels longitudinally extending substantially parallel to each other. A series of gaps extend from the first channel to the second channel to create a fluid communication path passing between a series of columns with the columns being longitudinally separated by a predetermined separation distance. The system also includes a first source configured to selectively introduce into the first channel a first biological composition at a first channel flow rate and a second source configured to selectively introduce into the second channel a second biological composition at a second channel flow rate. The sources are configured to create a differential between the first and second channel flow rates to generate physiological shear rates along the second channel that are bounded within a predetermined range.
The present invention relates to system and method for production of DNA particles and use thereof. The DNA particles can be produced by amplification of nucleic acid molecule(s). Alternatively, DNA particles can be prepared by condensing multiple DNA molecules. The DNA condensation into a particle is mainly triggered by pyrophosphate and positively charged cations (e.g. magnesium). DNA particles can be applied for numerous biological applications but not limited to directed evolution, proteomics, drug delivery and imaging. DNA particles can be used to synthesize proteins using in vitro transcription/translation reaction.
Streptococcus thermophilus comprising crRNA, Csm4, and Csm3 and use for cleavage of RNA bearing a nucleotide sequence complementary to the crRNA, in vitro or in vivo. Methods for site-specific cleavage/shredding of a target RNA molecule using an RNA-guided RNA endonuclease comprising a minimal complex of crRNA, Csm4, and Csm3, and methods of RNA knock-down and RNA knock-out are disclosed.
C07K 14/315 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from bacteria from Streptococcus (G), e.g. Enterococci
70.
Systems and methods for biomimetic fluid processing
Systems and methods generating physiologic models that can produce functional biological substances are provided. In some aspects, a system includes a substrate and a first and second channel formed therein. The channels extend longitudinally and are substantially parallel to each other. A series of apertures extend between the first channel and second channel to create a fluid communication path passing through columns separating the channels that extends further along the longitudinal dimension than other dimensions. The system also includes a first source configured to selectively introduce into the first channel a first biological composition at a first channel flow rate and a second source configured to selectively introduce into the second channel a second biological composition at a second channel flow rate, wherein the first channel flow rate and the second channel flow rate create a differential configured to generate physiological shear rates within a predetermined range in the channels.
Invention is related to novel compounds – benzenesulfonamides of general formulas (I) and (II). The compounds can be used in biomedicine as active ingredients in pharmaceutical formulations, because they inhibit enzymes which participate in disease progression. Acknowledgements: This research was funded by the European Social Fund under the Global Grant measure (no. VP1-3.1.-SMM-07-K-02-009).
C07D 215/08 - Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to the ring carbon atoms with acylated ring nitrogen atom
C07D 233/58 - Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring nitrogen atoms
C07C 311/16 - Sulfonamides having sulfur atoms of sulfonamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the sulfonamide groups bound to hydrogen atoms or to an acyclic carbon atom
C07D 235/08 - Radicals containing only hydrogen and carbon atoms
C07D 265/30 - 1,4-OxazinesHydrogenated 1,4-oxazines not condensed with other rings
C07D 209/08 - IndolesHydrogenated indoles with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to carbon atoms of the hetero ring
A method for producing a nucleic acid molecule from a template nucleic acid sequence and a linking unit attached to a primer, which method comprises a step of contacting the template nucleic acid sequence with a nucleic acid polymerase under conditions which allow the nucleic acid polymerase to produce the nucleic acid molecule from the primer based on the template nucleic acid sequence, wherein the linking unit is attached to a target site in the template nucleic acid sequence with a covalent linkage.
The compact lamp (1) consists of at least one light source (2), at least one focusing lens (3), a specially shaped secondary lens (4) with a saddle-shaped output surface, at least one light transmitting element (6), a battery holding chamber (8) with an electrical control circuit (9), which is connected to a button (11) for control of the lamp source via a magnetic contact (10). Some of these elements are placed inside the lamp housing, which is mounted on an end of a handlebar or another suitable lighting device, and some other elements, including the battery (7) and the magnetic control circuit, are installed inside the handlebar tube or the housing of the lighting device. The compact optical layout allows obtaining a beam, which is sharply limited in the vertical plane and sufficiently wide in the horizontal plane and is suitable for daytime running lamps, night headlamps or position lights.
The proposed antenna can be made from strips of a shape-memory alloy or other resilient material acting as a spring with attached branches that constitute individual monopole antennas. In the folded state, the antenna looks like a strip roll and can be placed on a satellite. When in orbit, the antenna automatically unfolds after the roll retention mechanism is released and orderly unfolds unrolling from a support frame or otherwise extends. The proposed design of monopole branches utilizes conductors of minimum length and achieves maximum directivity. Each monopole branch is connected to the signal receiver/transmitter by means of signal conduit elements. A system may include at least two such unfolding antennas thus achieving even greater operational effectiveness in regard to signal steerability, interference suppression and reduced moment of the satellite inertia. To prevent chaotic deployment of the antenna, additional measures are used that prevent unwinding of inner layers of the roll before the outer layer is extended.
Provided is a method for modifying a ssRNA at the 3' end, said method comprising contacting the strand with a ssRNA 2'-O-methyltransferase in the presence of a co-factor, under conditions which allow for the transfer by the ssRNA 2'-O-methyltransferase of a part of the co-factor onto 3' end of the ssRNA to form a modified ssRNA, wherein the ssRNA bears 2'-OH group at 3' terminal nucleotide and wherein the part of the co-factor transferred comprises a reporter group or a functional group.
A Type III-A CRISPR-Cas (St Csm) complex of Streptococcus thermophilus comprising crRNA, Csm4, and Csm3 and use for cleavage of RNA bearing a nucleotide sequence complementary to the crRNA, in vitro or in vivo. Methods for site-specific cleavage/shredding of a target RNA molecule using an RNA-guided RNA endonuclease comprising a minimal complex of crRNA, Csm4, and Csm3, and methods of RNA knock-down and RNA knock-out are disclosed. 999211.
C12N 15/11 - DNA or RNA fragmentsModified forms thereof
C07K 14/315 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from bacteria from Streptococcus (G), e.g. Enterococci
C12N 9/16 - Hydrolases (3.) acting on ester bonds (3.1)
The present invention generally relates to microfluidics and labeled nucleic acids. For example, certain aspects are generally directed to systems and methods for labeling nucleic acids within microfluidic droplets. In one set of embodiments, the nucleic acids may include "barcodes" or unique sequences that can be used to distinguish nucleic acids in a droplet from those in another droplet, for instance, even after the nucleic acids are pooled together. In some cases, the unique sequences may be incorporated into individual droplets using particles and attached to nucleic acids contained within the droplets (for example, released from lysed cells). In some cases, the barcodes may be used to distinguish tens, hundreds, or even thousands of nucleic acids, e.g., arising from different cells or other sources.
The present invention generally relates to microfluidics and labeled nucleic acids. For example, certain aspects are generally directed to systems and methods for labeling nucleic acids within microfluidic droplets. In one set of embodiments, the nucleic acids may include "barcodes" or unique sequences that can be used to distinguish nucleic acids hi a droplet from those in another droplet, for instance, even after the nucleic acids are pooled together. In some cases, the unique sequences may be incorporated into individual droplets using particles and attached to nucleic acids contained within the droplets (for example, released from lysed cells). In some cases, the barcodes may be used to distinguish tens, hundreds, or even thousands of nucleic acids, e.g., arising from different cells or other sources.
Systems and methods generating physiologic models that can produce functional biological substances are provided. In some aspects, a system includes a substrate and a first and second channel formed therein. The channels extend longitudinally and are substantially parallel to each other. A series of apertures extend between the first channel and second channel to create a fluid communication path passing through columns separating the channels that extends further along the longitudinal dimension than other dimensions. The system also includes a first source configured to selectively introduce into the first channel a first biological composition at a first channel flow rate and a second source configured to selectively introduce into the second channel a second biological composition at a second channel flow rate, wherein the first channel flow rate and the second channel flow rate create a differential configured to generate physiological shear rates within a predetermined range in the channels.
The goal is the improvement of technologies of modification of material properties by decreasing expenditures of energy and time and extending possibilities for modification of the materials by creating and maintaining a metastable state, which is characterized by a change in the structure of the material. The invention belongs to the technological field of manufacturing materials with desired properties, and in part to the field of methods of defect generation in crystals, and it can be applied in industries that apply the process of material doping with impurities in order to manufacture materials having a desired concentration of defects and an increased concentration of charge carriers, to create a metastable structural state of the material, as well as to measure energy and doses of radio waves.
H01L 21/00 - Processes or apparatus specially adapted for the manufacture or treatment of semiconductor or solid-state devices, or of parts thereof
H01L 21/268 - Bombardment with wave or particle radiation with high-energy radiation using electromagnetic radiation, e.g. laser radiation
H01L 21/263 - Bombardment with wave or particle radiation with high-energy radiation
H01L 21/326 - Application of electric currents or fields, e.g. for electroforming
H01L 31/068 - SEMICONDUCTOR DEVICES NOT COVERED BY CLASS - Details thereof adapted as photovoltaic [PV] conversion devices characterised by at least one potential-jump barrier or surface barrier the potential barriers being only of the PN homojunction type, e.g. bulk silicon PN homojunction solar cells or thin film polycrystalline silicon PN homojunction solar cells
H01L 31/18 - Processes or apparatus specially adapted for the manufacture or treatment of these devices or of parts thereof
H01L 21/22 - Diffusion of impurity materials, e.g. doping materials, electrode materials, into, or out of, a semiconductor body, or between semiconductor regionsRedistribution of impurity materials, e.g. without introduction or removal of further dopant
81.
METHOD FOR PRODUCTION OF BIOPOLYMER-BASED DROPLETS AND PARTICLES IN A MICROFLUIDIC SYSTEM
The present invention relates to micro-systems and methods for production of biopolymer-based droplets and particles. These particles can be used for encapsulation of biochemical, biological and/or therapeutic compounds. The encapsulated molecules can be released from particles into surrounding fluid over time and therefore potentially can be used as vesicles for drug transport and release. ˙
The proposed low correlated colour temperature phosphor converted LED is characterized by a small non-visual photobiological action to humans, which manifests itself as the suppression of melatonin secretion in the pineal gland, and can be used for the illumination of streets, car parking lots, pedestrian and bicycle tracks, building facades, monuments, parks and house yards that only slightly disrupts the circadian rhythm of humans. The LED has a semiconductor chip that emits short wavelength light in the blue, violet or near UV region due to the injection electroluminescence and a wavelength converter which converts the said short wavelength light due to photoluminescence to longer wavelength light having an orange component with the spectrum peaking in the range of about from 570 nm to 600 nm. In the case of partial conversion LED, the chip generates blue light that is partially converted to orange light by one phosphor (for instance, yttrium magnesium aluminium silicon garnet activated by trivalent cerium ions (Y3Mg2AISi2012:Ce3+), barium strontium silicon nitride activated by divalent europium ions ((Ba,Sr)2Si5N8:Eu2+), barium strontium orthosilicate, activated by divalent europium ions ((Ba,Sr)SiO4:Eu2+), calcium - alpha silicon aluminium oxynitride, activated by divalent europium ions (Ca-α-SiAlON:Eu2+), or calcium strontium selenide, activated by divalent europium ions ((Ca,Sr)Se:Eu2+)) contained in the converter. In the case of complete conversion LED, the chip generates near UV light that is completely absorbed in the converter and converted by a blue phosphor (for instance, CaMgSi2O6:Eu2+, Ba5SiO4Cl6:Eu2+, Mg3Ca3(PO4)4:Eu2+, (Ca,Sr,Ba)5(PO4)3CI :Eu2+, Ca2B5O9(Br,Cl):Eu2+, BaMgAl10O17:Eu2+,Mn2+, BaMg2Al16O27:Eu2+, (Lu,Gd)2SiO5:Ce3+, Sr2P2O7:Sn2+, SrSiAI2O3N2:Ce3+ or La3Si6N11 :Ce3+) and the orange phosphors mentioned above.
Streptococcus thermophilus CRISPR3/Cas system and use for cleavage of DNA bearing a nucleotide sequence complementary to the crRNA and a proto-spacer adjacent motif. Methods for site-specific modification of a target DNA molecule using an RNA-guided DNA endonuclease comprising at least one RNA sequence and at least one of an RuvC active site motif and an HNH active site motif; for conversion of Cas9 polypeptide into a nickase cleaving one strand of double-stranded DNA by inactivating one of the active sites (RuvC or HNH) in the polypeptide by at least one point mutation; for assembly of active polypeptide-polyribonucleotides complex in vivo or in vitro; and for re-programming a Cas9-crRNA complex specificity in vitro or using a cassette containing a single repeat-spacer-repeat unit.
A general method is proposed that permits incorporation of a photocaged selenocysteine residue in any desired position(s) of a protein utilizing UAG codon suppression by a genetically modified yeast strain. The protein carrying the selenocysteine residue(s) caged with a photoreactive nitrobenzyl group is expressed and purified from the yeast cells. The caging group is removed by illumination with UV light leaving the selenocysteine in place (inside cells or in purified protein preparation). The proposed method has a potential to simplify the synthesis of selenoproteins and therefore expand their biotechnological and biopharmaceutical utilization.˙
The present invention is related to polychromatic light sources of white light, which have spectral power distributions composed of at least three different components, such as clusters of coloured light-emitting diodes (LEDs) or LEDs with partial or complete conversion in phosphors. Disclosed are the peak wavelengths and relative partial radiant fluxes of the spectral components that allow rendering certain fractions of an extended colour palette with high fidelity and with increased chromatic saturation, respectively, and hence meeting subjective preferences to colour quality of illumination.
H05B 33/08 - Circuit arrangements for operating electroluminescent light sources
H01L 25/13 - Assemblies consisting of a plurality of individual semiconductor or other solid-state devices all the devices being of a type provided for in a single subclass of subclasses , , , , or , e.g. assemblies of rectifier diodes the devices having separate containers the devices being of a type provided for in group
H01L 25/075 - Assemblies consisting of a plurality of individual semiconductor or other solid-state devices all the devices being of a type provided for in a single subclass of subclasses , , , , or , e.g. assemblies of rectifier diodes the devices not having separate containers the devices being of a type provided for in group
86.
SYSTEM AND METHOD FOR A BIOMIMETIC FLUID PROCESSING
A system and method are provided for harvesting target biological substances. The system includes a substrate and a first and second channel formed in the substrate. The channels longitudinally extending substantially parallel to each other. A series of gaps extend from the first channel to the second channel to create a fluid communication path passing between a series of columns with the columns being longitudinally separated by a predetermined separation distance. The system also includes a first source configured to selectively introduce into the first channel a first biological composition at a first channel flow rate and a second source configured to selectively introduce into the second channel a second biological composition at a second channel flow rate. The sources are configured to create a differential between the first and second channel flow rates to generate physiological shear rates along the second channel that are bounded within a predetermined range.
G01N 33/48 - Biological material, e.g. blood, urineHaemocytometers
G06F 19/12 - for modelling or simulation in systems biology, e.g. probabilistic or dynamic models, gene-regulatory networks, protein interaction networks or metabolic networks
87.
SYSTEM AND METHOD FOR A BIOMIMETIC FLUID PROCESSING
A system and method are provided for harvesting target biological substances. The system includes a substrate and a first and second channel formed in the substrate. The channels longitudinally extending substantially parallel to each other. A series of gaps extend from the first channel to the second channel to create a fluid communication path passing between a series of columns with the columns being longitudinally separated by a predetermined separation distance. The system also includes a first source configured to selectively introduce into the first channel a first biological composition at a first channel flow rate and a second source configured to selectively introduce into the second channel a second biological composition at a second channel flow rate. The sources are configured to create a differential between the first and second channel flow rates to generate physiological shear rates along the second channel that are bounded within a predetermined range.
Invention is related to novel compounds - fluorinated benzenesulfonamides of general formula (I). The compounds can be used in biomedicine as active ingredients in pharmaceutical formulations, because they inhibit enzymes which participate in disease progression. ˙
C07D 295/096 - Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings
C07C 311/29 - Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound oxygen atoms having the sulfur atom of at least one of the sulfonamide groups bound to a carbon atom of a six-membered aromatic ring
C07C 311/39 - Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound nitrogen atoms, not being part of nitro or nitroso groups having the sulfur atom of at least one of the sulfonamide groups bound to a carbon atom of a six-membered aromatic ring having sulfur atoms of sulfonamide groups and amino groups bound to carbon atoms of six-membered aromatic rings of the same carbon skeleton having the nitrogen atom of at least one of the sulfonamide groups bound to hydrogen atoms or to an acyclic carbon atom
C07C 317/14 - SulfonesSulfoxides having sulfone or sulfoxide groups bound to carbon atoms of six-membered aromatic rings
C07C 317/18 - SulfonesSulfoxides having sulfone or sulfoxide groups and singly-bound oxygen atoms bound to the same carbon skeleton with sulfone or sulfoxide groups bound to acyclic carbon atoms of the carbon skeleton
C07C 317/36 - SulfonesSulfoxides having sulfone or sulfoxide groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton with sulfone or sulfoxide groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton having sulfone or sulfoxide groups and amino groups bound to carbon atoms of six-membered aromatic rings being part of the same non-condensed ring or of a condensed ring system containing that ring with the nitrogen atoms of the amino groups bound to hydrogen atoms or to carbon atoms
C07C 323/67 - Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and sulfur atoms, not being part of thio groups, bound to the same carbon skeleton containing sulfur atoms of sulfonamide groups, bound to the carbon skeleton
The goal of the invention is improvement of technologies of modification of material properties by decreasing expenditures of energy and time and extending possibilities for modification of materials by creating and maintaining a metastable state, which is characterized by a change in the structure of the material. The invention belongs to the technological field of manufacturing materials with desired properties, in part - to the field of methods of defect generation in crystals, and it can be applied in industries that apply the process of material doping with impurities in order to manufacture materials having a desired concentration of defects and an increased concentration of charge carriers, to create a metastable structural state of the material, as well as to measure energy and doses of radio waves.
H01L 21/428 - Bombardment with radiation with high-energy radiation using electromagnetic radiation, e.g. laser radiation
H01L 21/38 - Diffusion of impurity materials, e.g. doping materials, electrode materials, into, or out of, a semiconductor body, or between semiconductor regions
Provided is a method for modifying a strand of RNA at the 3' end, said method comprising contacting the strand with a RNA 2'-0-methyltransferase in the presence of a co-factor, under conditions which allow for the transfer by the RNA 2'-0-methyltransferase of a part of the co-factor onto the 3' end of the RNA strand to form a modified RNA strand, wherein the strand of RNA is comprised in a duplex, and wherein the part of the co-factor transferred comprises a reporter group or a functional group.
Isolation or in vitro assembly of the Cas9-crRNA complex of the Streptococcus thermophilus CRISPR3/Cas system and use for cleavage of DNA bearing a nucleotide sequence complementary to the crRNA and a proto-spacer adjacent motif. Methods for site-specific modification of a target DNA molecule in vitro or in vivo using an RNA-guided DNA endonuclease comprising RNA sequences and at least one of an RuvC active site motif and an HNH active site motif; for conversion of Cas9 polypeptide into a nickase cleaving one strand of double-stranded DNA by inactivating one of the active sites (RuvC or HNH) in the polypeptide by at least one point mutation; for assembly of active polypeptide-polyribonucleotides complex in vivo or in vitro; and for re-programming a Cas9-crRNA complex specificity in vitro and using a cassette containing a single repeat-spacer-repeat unit.
Isolation or in vitro assembly of the Cas9-crRNA complex of the Streptococcus thermophilus CRISPR3/Cas system and use for cleavage of DNA bearing a nucleotide sequence complementary to the crRNA and a proto-spacer adjacent motif. Methods for site-specific modification of a target DNA molecule using an RNA-guided DNA endonuclease comprising at least one RNA sequence and at least one of an RuvC active site motif and an HNH active site motif; for conversion of Cas9 polypeptide into a nickase cleaving one strand of double-stranded DNA by inactivating one of the active sites (RuvC or HNH) in the polypeptide by at least one point mutation; for assembly of active polypeptide-polyribonucleotides complex in vivo or in vitro; and for re-programming a Cas9-crRNA complex specificity in vitro or using a cassette containing a single repeat-spacer-repeat unit.
Isolation or in vitro assembly of the Cas9-crRNA complex of the Streptococcus thermophilus CRISPR3/Cas system and use for cleavage of DNA bearing a nucleotide sequence complementary to the crRNA and a proto-spacer adjacent motif. Methods for site-specific modification of a target DNA molecule in vitro or in vivo using an RNA-guided DNA endonuclease comprising RNA sequences and at least one of an RuvC active site motif and an HNH active site motif; for conversion of Cas9 polypeptide into a nickase cleaving one strand of double-stranded DNA by inactivating one of the active sites (RuvC or HNH) in the polypeptide by at least one point mutation; for assembly of active polypeptide-polyribonucleotides complex in vivo or in vitro; and for re-programming a Cas9-crRNA complex specificity in vitro and using a cassette containing a single repeat-spacer-repeat unit.
Isolation or in vitro assembly of the Cas9-crRNA complex of the Streptococcus thermophilus CRISPR3/Cas system and use for cleavage of DNA bearing a nucleotide sequence complementary to the crRNA and a proto-spacer adjacent motif Methods for site- specific modification of a target DNA molecule in vitro or in vivo using an RNA-guided DNA endonuclease comprising RNA sequences and at least one of an RuvC active site motif and an HNH active site motif; for conversion of Cas9 polypeptide into a nickase cleaving one strand of double-stranded DNA by inactivating one of the active sites (RuvC or HNH) in the polypeptide by at least one point mutation; for assembly of active polypeptide- polyribonucleotides complex in vivo or in vitro; and for re-programming a Cas9-crRNA complex specificity in vitro and using a cassette containing a single repeat-spacer-repeat unit.
A method for producing a nucleic acid molecule from a template nucleic acid sequence and a linking unit attached to a primer, which method comprises a step of contacting the template nucleic acid sequence with a nucleic acid polymerase under conditions which allow the nucleic acid polymerase to produce the nucleic acid molecule from the primer based on the template nucleic acid sequence, wherein the linking unit is attached to a target site in the template nucleic acid sequence with a covalent linkage.
Provided is a method for producing a nucleic acid molecule from a template nucleic acid sequence and a linking unit attached to a primer, which method comprises a step of contacting the template nucleic acid sequence with a nucleic acid polymerase under conditions which allow the nucleic acid polymerase to produce the nucleic acid molecule from the primer based on the template nucleic acid sequence, wherein the linking unit is attached to a target site in the template nucleic acid sequence with a covalent linkage.
patents
