Boston Medical Center Corporation

Seragen, Inc.

Cadence Design Systems, Inc.

Bayer Healthcare LLC

The University Hospital

John R Murphy

Diane P Williams

Joydeep Mitra

Taylor Elsom Hogan

Luke Roberto

Zachary Joseph Zumbo

Ryan Ratts

Terry Hermiston

Zhuozhi Wang

Ye Jin

Robert J Harrison

Shang Li

Ruth Winter

Li Sun

The present disclosure relates to electronic circuit design, and more specifically, to training a neural network to serve as the reward function for optimization-based approaches to PCB design automation. Embodiments may include generating, using a processor, one or more placed designs using a genetic optimization methodology including a reward function and adjusting the one or more placed designs and the reward function during the generating. Embodiments may further include routing the one or more placed designs using an auto-router to assign a routability score label and training a neural network, using the one or more placed designs and the routability score label, to extract one or more intermediate features from the one or more placed designs. Embodiments may also include predicting a routability of the PCB design based upon, at least in part, the one or more intermediate features.

System, method, and computer program product for optimization-based printed circuit board design

The present disclosure relates to systems and methods for floorplanning using machine learning techniques. Embodiments may include receiving an electronic design and analyzing the electronic design using a reinforcement learning agent. Embodiments may further include recommending a first action wherein the first action includes at least one of a place agent action, a via agent action, or a route agent action. Embodiments may also include updating the electronic design based upon, at least in part, the first action to generate an updated electronic design. Embodiments may further include analyzing the updated electronic design using the reinforcement learning agent and recommending a second action wherein the second action includes at least one of a place agent action, a via agent action, or a route agent action. Embodiments may also include updating the updated electronic design based upon the second action to generate a second updated electronic design.

System and method for autonomous printed circuit board design using machine learning techniques

Provided herein are protein biomarkers for NETosis related diseases, including proteases. Also provided are substrate sequences of such proteases and uses thereof.

Application of N-terminomics to NETosis in inflammation

Antibodies are disclosed that bind to and inhibit the anti-coagulant function of TFPI and have a lower affinity for TFPI at pH 6.0 than at pH 7.4. The lower affinity at pH 6 improves circulating half-life (T&#xbd;) due to reduced target mediated clearance, a process by which an antibody/antigen complex is endocytosed and trafficked to the lysosome where both components are degraded. The lower affinity at pH 6.0 results in disruption of the complex prior to lysosome targeting and allows for re-circulation of the antibody. Specific modifications to antibody binding by histidine residue substitution are disclosed along with methods of use.

Anti-TFPI antibody variants with differential binding across PH range for improved pharmacokinetics

The invention features methods for identifying compounds that inhibit cell death, and methods for identifying compounds that promote cell death, by blocking or accelerating, respectively, the translocation of the catalytic domain of toxins or transcription factors through the endosomal membrane into the cytosol of a cell. Also featured are methods for inhibiting cell death that include the administration of polypeptides that include a toxin consensus sequence recognized by one or more components of the cytosolic translocation factor complex.

Viral/bacterial toxin polypeptides and methods of using same

Disclosed is a therapeutic peptide useful in the treatment or prevention of infection caused by Gram-positive bacteria such as

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In vitro delivery of the diphtheria toxin (DT) catalytic (C) domain from the lumen of purified early endosomes to the external milieu requires the addition of both ATP and a cytosolic translocation factor (CTF) complex. The results presented here demonstrate that &#x3b2;-COP plays an essential role in the cytosolic release of the C-domain and is mediated by a consensus peptide sequence found on several bacterial toxins and in HIV-1 reverse transcriptase. The invention features methods for inhibiting cell death that include the administration of compounds based on this consensus sequence that inhibit the translocation of the catalytic domain of toxins or transcription factors. Also featured are methods for identifying compounds that inhibit cell death, and methods for identifying compounds that promote cell death by blocking or accelerating, respectively, the rate of toxin/factor endosomal translocation.

Methods for promoting, inhibiting and detecting toxin entry into cells

Disclosed is a method for identifying activators of a transition metal-dependent repressor of virulence gene expression in infectious prokaryotic pathogens. The method utilizes genetic circuitry that represents the response of a given prokaryote to nutritional stress and the expression of genes that contribute to the establishment of the infectious process. The exposure of recombinant cells or a cell-free system containing the genetic circuitry to a non-metal ion test substance that activates the repressor produces a detectable response. The method is applicable for any prokaryote employing metal ion-dependent repressors to regulate specific gene expression, specifically as it pertains to virulence determinant expression.

Identification of virulence determinants activators in prokaryotic pathogens

Disclosed is a hybrid molecule comprising a first part, a second part, and a third part connected by covalent bonds,

Hybrid molecules having translocation region and cell-binding region

Disclosed is a recombinant DNA molecule encoding a hybrid protein comprising a first part, a second part, and a third part,

Recombinant DNAS encoding three-part hybrid proteins

A chimeric toxin comprising protein fragments joined together by peptide bonds, the chimeric toxin comprising, in sequential order, beginning at the amino terminal end of the chimeric toxin,

DNA encoding chimeric toxin

A chimeric toxin comprising protein fragments joined together by peptide bonds, the chimeric toxin comprising, in sequential order, beginning at the amino terminal end of the chimeric toxin, (a) the enzymatically active Fragment A of diphtheria toxin, (b) a first fragment including the cleavage domain 1.sub.1 adjacent the Fragment A of diphtheria toxin, (c) a second fragment comprising at least a portion of the hydrophobic transmembrane region of Fragment B of diphtheria toxin, the second fragment having a deletion of at least 50 diphtheria toxin amino acid residues, the deletion being C-terminal to the portion of the transmembrane region, and the second fragment not including domain 1.sub.2, and (d) a third fragment comprising a portion of a cell-specific polypeptide ligand, the portion including at least a portion of the binding domain of the polypeptide ligand, the portion of the binding domain being effective to cause the chimeric toxin to bind selectively to a predetermined class of cells to be attacked by the enzymatically active Fragment A.

Chimeric toxins

A chimeric toxin comprising protein fragments joined together by peptide bonds, the chimeric toxin comprising, in sequential order, beginning at the amino terminal end of the chimeric toxin, (a) the enzymatically active Fragment A of diphtheria toxin, (b) a first fragment including the cleavage domain 1.sub.1 adjacent the Fragment A of diphtheria toxin, (c) a second fragment comprising at least a portion of the hydrophobic transmembrane region of Fragment B of diphtheria toxin, the second fragment having a deletion of at least 50 diphtheria toxin amino acid residues, the deletion being C-terminal to the portion of the transmembrane region, and the second fragment not including domain 1.sub.2, and (d) a third fragment comprising a portion of a cell-specific polypeptide ligand, the portion including at least a portion of the binding domain of the polypeptide ligand, the portion of the binding domain being effective to cause the chimeric toxin to bind selectively to a predetermined class of cells to be attacked by the enzymatically active Fragment A, the chimeric toxin possessing any of, greater toxicity than that of a toxin comprised of DAB.sub.486 fused to the third fragment, a lower K.sub.d for the sites on cells of the predetermined class to which the chimeric toxin binds than that of a toxin comprised of DAB.sub.486 fused to the third fragment, greater resistance to proteolytic degradation than that exhibited by a toxin comprised of DAB.sub.486 fused to the third fragment, greater resistance to the inhibition of its cytotoxicity by the cell-specific polypeptide ligand than that exhibited by DAB.sub.486 fused to the third fragment, the ability to inhibit protein synthesis to a given degree by a period of exposure that is shorter than the period of exposure required by DAB.sub.489 fused to the third fragment to inhibit protein synthesis to the same degree, or the ability to effect a more rapid onset of the inhibition of protein synthesis than that exhibited by DAB.sub.486 fused to the third fragment.

A hybrid molecule including a first part and a second part connected by a covalent bond,

Growing community of inventors

Boston, MA, United States of America

John R Murphy