Abstract: We evaluated the antibacterial activity of synthetic short proline-rich lipopeptides (SPRLPs) against clinically-relevant Gram-positive and Gram-negative pathogens. The short peptide sequence of SPRLPs were inspired by the repeating PXP motif apparent in longer PRAMPs. We assessed the potential of these SPRLPs to serve as adjuvants in combination with clinically-used antibiotics against P. aeruginosa. Our results revealed an amphiphilic non-hemolytic non-cytotoxic L-lipopeptide lead sequence that strongly potentiates minocycline and rifampicin against MDR/XDR P. aeruginosa. Furthermore, the adjuvant potency is retained in its enantiomeric D-SPRLP counterpart.

Abstract: Low permeability across the outer membrane is a major reason why most antibiotics are ineffective against Gram-negative bacteria. Agents that permeabilize the outer membrane are typically toxic at their effective concentrations. Here, we report the development of a broad-spectrum homodimeric tobramycin adjuvant that is non-toxic and more potent than the gold standard permeabilizing agent, polymyxin B nonapeptide. In pilot studies, the adjuvant confers potent bactericidal activity on novobiocin against Gram-negative bacteria, including carbapenem-resistant and colistin-resistant strains bearing plasmid-borne mcr-1 genes. Resistance development to the combination was significantly reduced, relative to novobiocin alone, and there was no induction of cross-resistance to other antibiotics, including the gyrase-acting fluoroquinolones. Tobramycin homodimer may allow the use of lower doses of novobiocin, overcoming its twin-problem of efficacy and toxicity.

Abstract: A method for controlling an SCR catalytic converter (20, 30), comprising detecting (200) concentration values (314, 324; 414, 424) in the exhaust gas downstream of the catalytic converter (20), wherein at least one concentration value for NH3 and one concentration value for NOx is detected; calculating (202) modeled concentration values (316, 322; 416, 422) for NH3 and NOx downstream of the catalytic converter on the basis of a catalytic converter model, wherein the model comprises an aging parameter (342, 442) which at least partially describes aging of the modeled catalytic converter; comparing (208) the detected concentration values with the modeled concentration values; and, in a manner dependent on the result of the comparison, changing the aging parameter (342, 442) of the model and/or changing a predefined dosing quantity for a reducing agent in the SCR catalytic converter.

Abstract: Glycosylated antitumor ether lipids (GAELs) are effective cytotoxic agents against cancer stem cells. Furthermore, combining GAELs which kill cells by a caspase-independent pathway with agents that kill cells by apoptosis will lead to elimination of the differentiated tumor cells and the undifferentiated cancer stem cells leading to an elimination of the tumor and preventing recurrence.

Abstract: Herein, we describe the development of non-?-lactam-based potentiator molecules that synergize with ?-lactam antibiotics and ?-lactam-?-lactamase inhibitor combinations against MDR/XDR P. aeruginosa phenotypes. The compound comprises a chemical structure or chemical formula of Formula (A) or a suitable salt form thereof, wherein “n” is a carbon tether having a length of between about 2-18 carbons.

Abstract: A secondary fatty acyl component of varying length was added onto the polymyxin structure at the amine side-chain of L-diaminobuytric acid at position 1, resulting to the development of dilipid polymyxins. The incorporation of an additional lipid was found to confer to polymyxin activity against Gram-positive bacteria, to which polymyxins are inherently inactive against The dilipid polymyxins showed selective antibacterial activity against Pseudomonas aeruginosa. Moreover, dilipid polymyxin 1 that consists of four carbon-long aliphatic lipids displayed the ability to enhance the antibacterial potency of other antibiotics in combination against P. aeruginosa, thereby resembling the adjuvant activity of the well-known outer membrane permeabilizer polymyxin B nonapeptide (PMBN).

Abstract: A method for controlling an SCR catalytic converter (20, 30), comprising detecting (200) concentration values (314, 324; 414, 424) in the exhaust gas downstream of the catalytic converter (20), wherein at least one concentration value for NH3 and one concentration value for NOx is detected; calculating (202) modeled concentration values (316, 322; 416, 422) for NH3 and NOx downstream of the catalytic converter on the basis of a catalytic converter model, wherein the model comprises an aging parameter (342, 442) which at least partially describes aging of the modeled catalytic converter; comparing (208) the detected concentration values with the modeled concentration values; and, in a manner dependent on the result of the comparison, changing the aging parameter (342, 442) of the model and/or changing a predefined dosing quantity for a reducing agent in the SCR catalytic converter.

Abstract: The invention concerns a method for controlling an SCR catalytic converter. A first modelled level of ammonia (NH3_mod1) and a second modelled level of ammonia (NH3_mod2) of the SCR catalytic converter are determined from two different models. The second modelled level of ammonia (NH3_mod2) is assessed by comparing it with the first modelled level of ammonia (NH3_mod1).

Abstract: We evaluated the antibacterial activity of synthetic short proline-rich lipopeptides (SPRLPs) against clinically-relevant Gram-positive and Gram-negative pathogens. The short peptide sequence of SPRLPs were inspired by the repeating PXP motif apparent in longer PRAMPs. We assessed the potential of these SPRLPs to serve as adjuvants in combination with clinically-used antibiotics against P. aeruginosa. Our results revealed an amphiphilic non-hemolytic non-cytotoxic L-lipopeptide lead sequence that strongly potentiates minocycline and rifampicin against MDR/XDR P. aeruginosa. Furthermore, the adjuvant potency is retained in its enantiomeric D-SPRLP counterpart.

Abstract: Glycosylated Antitumor Ether Lipids (GAELs) kill cancer cells by a nonapoptotic pathway which is an attractive strategy to avoid resistance. To further optimize the antitumor effect, we prepared various analogs of di-, and tri-cationic GAEL analogs differing in the nature of the sugar (D-glucose or L-glucose), the anomeric linkage as well as position of the glycerolipid moiety. The di- and tri-cationic GAELs were synthesized and their in vitro anticancer properties were evaluated against drug resistant and aggressively growing cancer cell lines derived from human breast, prostate, pancreatic and ovarian cancers. The most potent dicationic GAEL analogs were also studied against cancer stem cells obtained from breast BT 474, prostate DU145 and ovarian A2780cp cell lines. Our results indicate that the number of positive charges, the position of the amino substituents and the nature of the sugar have significant effects on the anticancer activities of these compounds.

Abstract: A method (300) for operating an SCR catalytic converter system which has a first SCR catalytic converter (12) and a second SCR catalytic converter, characterized by a step of controlling (310) an NH3 mass flow after the first SCR catalytic converter (12).

Abstract: A method for determining a mass flow of ammonia between two SCR catalytic converters disposed one after the other in an SCR catalytic converter system in an exhaust system, which comprises only one reduction agent dosing unit upstream of the first SCR catalytic converter, characterized in that the determination is carried out from the signal of a NOx sensor disposed between the two SCR catalytic converters and the signal of a NOx sensor disposed downstream of the second SCR catalytic converter.

Abstract: The invention concerns a method for controlling an SCR catalytic converter. A first modelled level of ammonia (NH3_mod1) and a second modelled level of ammonia (NH3_mod2) of the SCR catalytic converter are determined from two different models. The second modelled level of ammonia (NH3_mod2) is assessed by comparing it with the first modelled level of ammonia (NH3_mod1).

Abstract: A method (300) for operating an SCR catalytic converter system which has a first SCR catalytic converter (12) and a second SCR catalytic converter, characterized by a step of controlling (310) an NH3 mass flow after the first SCR catalytic converter (12).

Abstract: A method for determining a mass flow of ammonia between two SCR catalytic converters disposed one after the other in an SCR catalytic converter system in an exhaust system, which comprises only one reduction agent dosing unit upstream of the first SCR catalytic converter, characterized in that the determination is carried out from the signal of a NOx sensor disposed between the two SCR catalytic converters and the signal of a NOx sensor disposed downstream of the second SCR catalytic converter.

Abstract: Glycosylated Antitumor Ether Lipids (GAELs) kill cancer cells by a nonapoptotic pathway which is an attractive strategy to avoid resistance. To further optimize the antitumor effect, we prepared various analogs of di-, and tri-cationic GAEL analogs differing in the nature of the sugar (D-giucose or L-glucose), the anomeric linkage as well as position of the glycerolipid moiety. The di- and tri-cationic GAELs were synthesized and their in vitro anticancer properties were evaluated against drug resistant and aggressively growing cancer cell lines derived from human breast, prostate, pancreatic and ovarian cancers. The most potent dicationic GAEL analogs were also studied against cancer stem cells obtained from breast BT 474, prostate DU145 and ovarian A2780cp cell lines. Our results indicate that the number of positive charges, the position of the amino substituents and the nature of the sugar have significant effects on the anticancer activities of these compounds.

Abstract: In a method for operating an SCR catalytic converter provided for the reduction of NOx in exhaust gases of an internal combustion engine, which SCR catalytic converter is operated with a reagent which can be stored in the SCR catalytic converter such that there is a certain reagent fill level in the SCR catalytic converter, wherein the actual NOx concentration downstream of the SCR catalytic converter is monitored on the basis of the signal of a sensor, which is arranged downstream of the SCR catalytic converter and which is sensitive at least with respect to NOx, in comparison with a calculated NOx concentration downstream of the SCR catalytic converter, it is provided according to the invention that, in the case of a comparison result which represents a conversion deficit as a difference between the measured actual NOx concentration and the previous calculated reagent fill level in the SCR catalytic converter is corrected to a new calculated reagent fill level, whereby an immediate dosing of reagent takes p

Abstract: In some aspects, the present invention provides aminoglycoside derivatives thereof that exhibit antibacterial activity. In some aspects, the aminoglycoside derivatives comprise compounds consisting of (a) an ammoglycoside group and (b) at least one hydrophobic carbamate and alkoxy group to the primary or secondary hydroxy position of the aminolvcoside group and salts thereof. Additionally, methods of treating and preventing bacterial infections using the aminoglycoside derivatives are also provided.

Abstract: Glycosylated antitumor ether lipids (GAELs) are effective cytotoxic agents against cancer stem cells. Furthermore, combining GAELs which kill cells by a caspase-independent pathway with agents that kill cells by apoptosis will lead to elimination of the differentiated tumor cells and the undifferentiated cancer stem cells leading to an elimination of the tumor and preventing recurrence.

Abstract: Hydrophobically enhanced aminoglycosides have been prepared and shown to be effective antibacterial agents. These agents may be used in the treatment or prevention of various bacterial infections. Methods of preparing these agents also permit facile synthetic access. Formula (I).