Abstract: Among other things, the present disclosure provides technologies for altering splicing, particularly for increasing inclusion of exons in splicing products. In some embodiments, the present disclosure provides SMN2 oligonucleotides, compositions, and methods thereof. In some embodiments, the present disclosure provides chirally controlled SMN2 oligonucleotide compositions. In some embodiments, provided oligonucleotides and compositions can increase level of an exon 7-containing SMN2 splicing product and/or a gene product thereof. In some embodiments, the present disclosure provides methods for treatment of splicing-related conditions, disorders and diseases. In some embodiments, the present disclosure provides methods for treating SMN2-related conditions, disorders and diseases such as SMA (spinal muscular atrophy) and ALS (amyotrophic lateral sclerosis).

Abstract: Among other things, the present disclosure provides designed APOC3 oligonucleotides, compositions, and methods thereof. In some embodiments, provided oligonucleotide compositions provide improved single-stranded RNA interference and/or RNase H-mediated knockdown. Among other things, the present disclosure encompasses the recognition that structural elements of oligonucleotides, such as base sequence, chemical modifications (e.g., modifications of sugar, base, and/or internucleotidic linkages) or patterns thereof, conjugation with additional chemical moieties, and/or stereochemistry [e.g., stereochemistry of backbone chiral centers (chiral internucleotidic linkages)], and/or patterns thereof, can have significant impact on oligonucleotide properties and activities, e.g., RNA interference (RNAi) activity, stability, delivery, etc.

Abstract: The present disclosure pertains to the recognition that immune responses mediated by CpG oligonucleotides can be affected by the stereochemistry of modified internucleotidic linkages such as phosphorothioates. In some embodiments, the present disclosure relates to chirally controlled CpG oligonucleotide compositions comprising CpG oligonucleotides comprising multiple modified internucleotidic linkages such as phosphorothioate linkages, wherein the oligonucleotides comprise one or more CpG region motifs having defined stereochemistry patterns of chiral internucleotidic linkages. In some embodiments, CpG oligonucleotides comprising one or more CpG region motifs are capable of agonizing an immune response. In some embodiments, CpG oligonucleotides comprising one or more CpG region motifs are antagonistic. Methods for making and using chirally controlled CpG oligonucleotide compositions are also described.

Abstract: A fuel cell reversal event is diagnosed by integrating current density via a controller in response to determine an accumulated charge density. The controller executes a control action when the accumulated charge density exceeds a threshold, including recording a diagnostic code indicative of event severity. The control action may include continuing stack operation at reduced power capability when the accumulated charge density exceeds a first threshold and shutting off the stack when the accumulated charge density exceeds a higher second threshold. The event may be detected by calculating a voltage difference between an average and a minimum cell voltage, and then determining if the difference exceeds a voltage difference threshold. The charge density thresholds may be adjusted based on age, state of health, and/or temperature of the fuel cell or stack. A fuel cell system includes the stack and controller.

Abstract: The present disclosure discloses a display device. The display device includes an interface wherein the interface obtains content to be displayed, and a plurality of display components each having a front display surface to output sub-content. The sub-content is a portion of the content to be displayed. The display device further includes an adjustment assembly. The adjustment assembly moves one or more of the display components in a direction perpendicular to a front display plane.

Abstract: Among other things, the present disclosure provides oligonucleotides, compositions, and methods thereof. Among other things, the present disclosure encompasses the recognition that structural elements of oligonucleotides, such as base sequence, chemical modifications (e.g., modifications of sugar, base, and/or internucleotidic linkages) or patterns thereof, conjugation with additional chemical moieties, and/or stereochemistry [e.g., stereochemistry of backbone chiral centers (chiral internucleotidic linkages)], and/or patterns thereof, can have significant impact on oligonucleotide properties and activities, e.g., knockdown ability, stability, delivery, etc. In some embodiments, the oligonucleotides decrease the expression, activity and/or level of a C9orf72 gene, including but not limited to, one comprising a repeat expansion, or a gene product thereof.

Abstract: Among other things, the present disclosure provides oligonucleotides, compositions, and methods thereof. Among other things, the present disclosure encompasses the recognition that structural elements of oligonucleotides, such as base sequence, chemical modifications (e.g., modifications of sugar, base, and/or internucleotidic linkages) or patterns thereof, conjugation with additional chemical moieties, and/or stereochemistry [e.g., stereochemistry of backbone chiral centers (chiral internucleotidic linkages)], and/or patterns thereof, can have significant impact on oligonucleotide properties and activities, e.g., knockdown ability, stability, delivery, etc. In some embodiments, the oligonucleotides decrease the expression, activity and/or level of a C9orf72 gene, including but not limited to, one comprising a repeat expansion, or a gene product thereof.

Abstract: A controller-executed method for conditioning a membrane electrode assembly (MEA) in a fuel cell for use in a fuel cell stack includes humidifying a fuel inlet to the stack to a threshold relative humidity level, and maintaining a current density and cell voltage of the fuel cell at a calibrated current density level and hold voltage level, respectively, via the controller in at least one voltage recovery stage. The recovery stage has a predetermined voltage recovery duration. The method includes measuring the cell voltage after completing the predetermined voltage recovery duration, and executing a control action with respect to the fuel cell or fuel cell stack responsive to the measured cell voltage exceeding a target voltage, including recording a diagnostic code via the controller indicative of successful conditioning of the MEA. A fuel cell system includes the fuel cell stack and controller.

Abstract: Among other things, the present disclosure provides designed PNPLA3 oligonucleotides, compositions, and methods thereof. In some embodiments, provided oligonucleotide compositions provide improved single-stranded RNA interference and/or RNase H-mediated knockdown. Among other things, the present disclosure encompasses the recognition that structural elements of oligonucleotides, such as base sequence, chemical modifications (e.g., modifications of sugar, base, and/or internucleotidic linkages) or patterns thereof, conjugation with additional chemical moieties, and/or stereochemistry [e.g., stereochemistry of backbone chiral centers (chiral internucleotidic linkages)], and/or patterns thereof, can have significant impact on oligonucleotide properties and activities, e.g., RNA interference (RNAi) activity, stability, delivery, etc.

Abstract: Among other things, the present disclosure provides designed oligonucleotides, compositions, and methods thereof. In some embodiments, provided oligonucleotide compositions provide improved single-stranded RNA interference and/or RNase H-mediated knockdown. Among other things, the present disclosure encompasses the recognition that structural elements of oligonucleotides, such as base sequence, chemical modifications (e.g., modifications of sugar, base, and/or internucleotidic linkages) or patterns thereof, conjugation with additional chemical moieties, and/or stereochemistry [e.g., stereochemistry of backbone chiral centers (chiral internucleotidic linkages)], and/or patterns thereof, can have significant impact on oligonucleotide properties and activities, e.g., RNA interference (RNAi) activity, stability, delivery, etc.

Abstract: A fuel cell system that includes a component for removing anionic contaminants is provided. The fuel system including a fuel cell stack, a fuel gas feed subsystem in communication with fuel cell anodes in the fuel cell stack, an oxygen-containing gas feed subsystem system in communication with fuel cell cathodes in the fuel cell stack, and an anionic scavenging subsystem in communication with the fuel gas feed subsystem and/or the an oxygen-containing gas feed subsystem.

Abstract: Among other things, the present disclosure relates to designed oligonucleotides, compositions, and methods thereof. In some embodiments, provided oligonucleotide compositions provide altered splicing of a transcript. In some embodiments, provided oligonucleotide compositions have low toxicity. In some embodiments, provided oligonucleotide compositions provide improved protein binding profiles. In some embodiments, provided oligonucleotide compositions have improved delivery. In some embodiments, provided oligonucleotide compositions have improved uptake. In some embodiments, the present disclosure provides methods for treatment of diseases using provided oligonucleotide compositions.

Abstract: Among other things, the present disclosure relates to designed oligonucleotides, compositions, and methods thereof. In some embodiments, provided oligonucleotide compositions provide altered splicing of a transcript. In some embodiments, provided oligonucleotide compositions have low toxicity. In some embodiments, provided oligonucleotide compositions provide improved protein binding profiles. In some embodiments, provided oligonucleotide compositions have improved delivery. In some embodiments, provided oligonucleotide compositions have improved uptake. In some embodiments, the present disclosure provides methods for treatment of diseases using provided oligonucleotide compositions.

Abstract: A method for reducing fuel cell voltage loss in a fuel cell that includes an anode catalyst layer including an anode catalyst and a cathode catalyst layer including a cathode catalyst with a proton exchange layer interposed between the anode catalyst layer and the cathode catalyst layer. The method includes a step of initiating shutdown of the fuel cell. Carbon monoxide or carbon monoxide-like species contaminating the anode catalyst is oxidized during shutdown such that carbon monoxide or carbon monoxide-like species is removed from the anode catalyst.

Abstract: In some embodiments, the present disclosure pertains to compositions and methods related to delivery of a biologically active agent, wherein the compositions comprise a biologically active agent and a lipid. In various embodiments, the lipid is selected from: lauric acid, myristic acid, palmitic acid, stearic acid, oleic acid, linoleic acid, alpha-linolenic acid, gamma-linolenic acid, docosa-hexaenoic acid (cis-DHA), turbinaric acid and dilinoleyl. In some embodiments, a composition and method are useful for delivery of a biologically active agent to a particular cell or tissue, e.g., a muscle cell or tissue.

Abstract: The present disclosure pertains to the recognition that immune responses mediated by CpG oligonucleotides can be affected by the stereochemistry of modified internucleotidic linkages such as phosphorothioates. In some embodiments, the present disclosure relates to chirally controlled CpG oligonucleotide compositions comprising CpG oligonucleotides comprising multiple modified internucleotidic linkages such as phosphorothioate linkages, wherein the oligonucleotides comprise one or more CpG region motifs having defined stereochemistry patterns of chiral internucleotidic linkages. In some embodiments, CpG oligonucleotides comprising one or more CpG region motifs are capable of agonizing an immune response. In some embodiments, CpG oligonucleotides comprising one or more CpG region motifs are antagonistic. Methods for making and using chirally controlled CpG oligonucleotide compositions are also described.

Abstract: A fuel cell reversal event is diagnosed by integrating current density via a controller in response to determine an accumulated charge density. The controller executes a control action when the accumulated charge density exceeds a threshold, including recording a diagnostic code indicative of event severity. The control action may include continuing stack operation at reduced power capability when the accumulated charge density exceeds a first threshold and shutting off the stack when the accumulated charge density exceeds a higher second threshold. The event may be detected by calculating a voltage difference between an average and a minimum cell voltage, and then determining if the difference exceeds a voltage difference threshold. The charge density thresholds may be adjusted based on age, state of health, and/or temperature of the fuel cell or stack. A fuel cell system includes the stack and controller.

Abstract: The present disclosure discloses a display device. The display device includes an interface wherein the interface obtains content to be displayed, and a plurality of display components each having a front display surface to output sub-content. The sub-content is a portion of the content to be displayed. The display device further includes an adjustment assembly. The adjustment assembly moves one or more of the display components in a direction perpendicular to a front display plane.

Abstract: A controller-executed method for conditioning a membrane electrode assembly (MEA) in a fuel cell for use in a fuel cell stack includes humidifying a fuel inlet to the stack to a threshold relative humidity level, and maintaining a current density and cell voltage of the fuel cell at a calibrated current density level and hold voltage level, respectively, via the controller in at least one voltage recovery stage. The recovery stage has a predetermined voltage recovery duration. The method includes measuring the cell voltage after completing the predetermined voltage recovery duration, and executing a control action with respect to the fuel cell or fuel cell stack responsive to the measured cell voltage exceeding a target voltage, including recording a diagnostic code via the controller indicative of successful conditioning of the MEA. A fuel cell system includes the fuel cell stack and controller.

Abstract: Among other things, the present disclosure relates to designed oligonucleotides, compositions, and methods thereof. In some embodiments, provided oligonucleotide compositions provide altered splicing of a transcript. In some embodiments, provided oligonucleotide compositions have low toxicity. In some embodiments, provided oligonucleotide compositions provide improved protein binding profiles. In some embodiments, provided oligonucleotide compositions have improved delivery. In some embodiments, provided oligonucleotide compositions have improved uptake. In some embodiments, the present disclosure provides methods for treatment of diseases using provided oligonucleotide compositions.