Abstract: A two-chain insulin analogue contains an A chain modified by (i) a monomeric glucose-binding element at or near its N terminus and (ii) a B chain modified by at or near its C terminus by an element that reversibly binds to the monomeric glucose-binding element such that this linkage is displaceable by glucose. The monomeric glucose-binding element may be phenylboronic acid derivative (optionally halogenated). The B chain may be modified by a diol-containing element derived from a monosaccharide, disaccharide or oligosaccharide, a non-saccharide diol-containing moiety or a ?-hydroxycarboxylate-containing moiety. The analogue can be manufactured by trypsin-mediated semi-synthesis. Formulations can be at strengths U-10 to U-1000 in soluble solutions at pH 7.0-8.0 with or without zinc ions at a molar ratio of 0.0-3.0 ions per insulin analogue monomer.

Abstract: An insulin analogue comprises an insulin B-chain polypeptide containing a Trp substitution at position B26 relative to the sequence of wild-type insulin. The insulin analogue may additionally comprise an OrnB29 substitution, a C-terminal extension of one or two basic amino acids such as Arg-Arg, a GlnB13 substitution, a GlyA21 substitution, a HisA8 or ArgA8 substitution, or a combination thereof. The insulin analogue may be formulated in the presence of zinc ions at a molar ratio of 2.2-10 zinc ions per six insulin analogue monomers. The molecular design is believed to stabilize the dimer interface of insulin (and its stable formulation as a zinc insulin hexamer) by means of aromatic amino-acid substitutions at position B26 of the B chain. The insulin analogs of the present invention may have two chains (A and B) as in mammalian insulins or may be engineered with a C domain (4-12 amino acids in length) to provide a single-chain.

Abstract: The present invention provides rapid-acting insulin and insulin analogue formulations. The invention further provides delivery devices, particularly infusion sets, which allow for the rapid absorption of insulin and insulin analogues, as well as other active agents. Methods of using the insulin and insulin analogue formulations as well as the insulin delivery devices for treating subjects with diabetes mellitus are also provided.

Abstract: The present invention relates to a method for producing a subassembly having a form-fitting connection with a precipitation-hardened form-fitting region as well as a corresponding subassembly, wherein at least two components of a subassembly are provided that are connected together in form-fitting manner, wherein each of the components has a form-fitting region that can come in contact with at least one other form-fitting region of the other component to be connected, in order to produce a form-fitting connection by limiting at least one degree of freedom of movement of the connected components relative to one another, wherein at least one of the components has at least one deformation form-fitting region for providing the form-fitting connection that is reshaped for producing the form-fitting connection after arranging the components to be connected relative to one another, in order to produce the form-fitting connection.

Abstract: A sensor arrangement for determining at least one measurand of a measuring medium includes at least one first sensor with a first sensing element used to record measured values of a first measurand of the measuring medium, a housing having a housing wall which surrounds a housing interior containing the first sensing element, wherein the housing interior contains a medium in particular, a liquid which has a predetermined value of the first measurand.

Abstract: An insulin analogue comprises an insulin A-chain polypeptide and an insulin B-chain polypeptide. The A-chain polypeptide contains a Glu substitution at a position corresponding to position A8, and an Ala, Glu, Gln, His, Tyr, Phe or Trp substitution at a position A13, relative to wild type insulin. The B-chain polypeptide contains a cyclohexanylalanine substitution at position B24, relative to wild type insulin. The analogue may be an analogue of a mammalian insulin, such as human insulin. A nucleic acid encoding such an insulin analogue is also provided. A method of lowering the blood sugar of a patient comprises administering a physiologically effective amount of the insulin analogue or a physiologically acceptable salt thereof to a patient.

Abstract: A single-chain insulin comprises a C-domain of 6 to 11 amino acid residues comprising at least two acidic residues at the N-terminal side of the C-domain and at least two basic residues at the C-terminal side of the C-domain peptide, a basic amino acid residue at the position corresponding to A8 of human insulin, and an acidic amino acid residue at the position corresponding to A14 of human insulin. The C-domain may contain a 2 to 4 amino acid joint region between the acidic and basic residues. Residues C1 and C2 may have a net negative charge of ?1 or ?2; and the remaining C-domain segment may culminates with two basic residues. A pharmaceutical composition comprises the single-chain insulin, formulated at a pH within the range 7.0 to 8.0, and may be formulated at a concentration of 0.6 mM to 5.0 mM and/or at a strength of U-100 to U-1000.

Abstract: A two-chain insulin analogue contains Aspartic Acid at position B10 and penta-fluoro-Phenylalanine at position B24, optionally Histidine or Glutamic Acid at position A8, optionally additional substitutions or modifications at positions A13 and/or A14 and/or B28 and/or B29. The analogue may be an analogue of a mammalian insulin, such as human insulin, may optionally include (i) N-terminal deletion of one, two or three residues from the B chain, (ii) a mono-peptide or dipeptide C-terminal extension of the B-chain containing at least one acidic residue, and (iii) other modifications known in the art to enhance the stability of insulin. Formulations of the above analogues at successive strengths U-100 to U-1000 in soluble solutions at at least pH value in the range 7.0-8.0 in the absence or presence of zinc ions at a molar ratio of 0.00-0.10 zinc ions per insulin analogue monomer.

Abstract: A heater comprising: (a) a film; (b) one or more coverings that extends along one or more sides of the film; and (c) one or more power application portions that apply power to the film so that the film heats up; wherein the film is a graphite film.

Abstract: A two-chain insulin analog contains Aspartic Acid at position B10 and penta-fluoro-Phenylalanine at position B24, optionally Histidine or Glutamic Acid at position A8, optionally additional substitutions or modifications at positions A13 and/or A14 and/or B28 and/or B29. The analog may be an analog of a mammalian insulin, such as human insulin, may optionally include (i) N-terminal deletion of one, two or three residues from the B chain, (ii) a mono-peptide or dipeptide C-terminal extension of the B-chain containing at least one acidic residue, and (iii) other modifications known in the art to enhance the stability of insulin. Formulations of the above analogs at successive strengths U-100 to U-1000 in soluble solutions at least pH value in the range 7.0-8.0 in the absence or presence of zinc ions at a molar ratio of 0.00-0.10 zinc ions per insulin analog monomer.

Abstract: A two-chain insulin analogue contains a modified A-chain polypeptide and a modified B-chain polypeptide. The A-chain polypeptide comprises one or more of: a His or Glu substitution at position A8, a Glu substitution at position A14; and a Gln or Arg substitution at positon A17. The B-chain polypeptide comprises one or more of: a deletion of the amino acids at position B1, B1-B2, B1-B3, B30 or a combination thereof; an Ala or Glu substitution at position B2; a Glu substitution at position B3. The analogue exhibits thermodynamic stability in a zinc-free solution, decreased self-association, maintains biological potency, and no increased mitogenicity. The analogue exhibits resistance to chemical degradation and physical degradation. A method of treating a patient with diabetes mellitus or obesity comprises administering a physiologically effective amount of the insulin analogue or a physiologically acceptable salt thereof to a patient.

Abstract: A sensor arrangement for determining at least one measurand of a measuring medium includes at least one first sensor with a first sensing element used to record measured values of a first measurand of the measuring medium, a housing having a housing wall which surrounds a housing interior containing the first sensing element, wherein the housing interior contains a medium in particular, a liquid which has a predetermined value of the first measurand.

Abstract: The present disclosure relates to a spectrometric measuring device for a process measuring point including a housing, a radiation source arranged in the housing, a coupling and decoupling optical system to direct radiation from the radiation source into a measuring region and to couple measuring radiation from the measuring region into the housing, a spectrograph arranged in the housing and aligned such that the measuring radiation is detected by the spectrograph with a detector, an electronic device arranged in the housing and connected to the detector and configured to detect a spectrum from the spectrograph and to process it to determine a concentration of an analyte in the measuring medium or a value derived therefrom, and a connection connected to the housing for connecting the housing to a process container, wherein the measuring region is located within a volume of the process container, said volume containing the measuring medium.

Abstract: A single-chain insulin comprises a C-domain of 6 to 11 amino acid residues comprising at least two acidic residues at the N-terminal side of the C-domain and at least two basic residues at the C-terminal side of the C-domain peptide, a basic amino acid residue at the position corresponding to A8 of human insulin, and an acidic amino acid residue at the position corresponding to A14 of human insulin. The C-domain may contain a 2 to 4 amino acid joint region between the acidic and basic residues. Residues C1 and C2 may have a net negative charge of ?1 or ?2; and the remaining C-domain segment may culminates with two basic residues. A pharmaceutical composition comprises the single-chain insulin, formulated at a pH within the range 7.0 to 8.0, and may be formulated at a concentration of 0.6 mM to 5.0 mM and/or at a strength of U-100 to U-1000.

Abstract: A hand-held power-tool device includes at least one coupling device, which has at least one contact receiving region, and which is configured to couple an optional additional module to at least one energy supply unit, in at least one operating state. The at least one contact receiving region has (i) at least one receiving opening configured to receive a corresponding contact element of the optional additional module, and (ii) at least one dirt removal opening.

Abstract: A coolant pump (1) of an internal combustion engine, having a pump casing (2), in which a pump shaft (3) is rotatably supported by a water pump bearing assembly (4) and an impeller (6) connected in a rotationally fixed manner to the pump shaft (3) is associated with an intake space (7). During a rotation of the impeller (6) together with associated blades (8), a coolant as a working medium is pumped from the intake space (7), via a coolant outlet of the coolant pump (1), into a cooling system of the internal combustion engine. A dirt trap is associated as a functional module (12a) with the impeller (6) on a side facing away from the intake space (7), wherein the working medium flows into the functional module (12a) from the intake space via at least one opening (13) introduced into the impeller and emerges via a flow outlet (15a).

Abstract: An insulin analogue comprises a B-chain polypeptide containing a cyclohexanylalanine substitution at position B24 and optionally containing additional amino-acid substitutions at positions A8, B28, and/or B29. A proinsulin analogue or single-chain insulin analogue contains a B domain containing a cyclohexanylalanine substitution at position B24 and optionally contains additional amino-acid substitutions at positions A8, B28, and/or B29. The analogue may be an analogue of a mammalian insulin, such as human insulin. A nucleic acid encoding such an insulin analogue is also provided. A method of lowering the blood sugar of a patient comprises administering a physiologically effective amount of the insulin analogue or a physiologically acceptable salt thereof to a patient. A method of semi-synthesis using an unprotected octapeptide by means of modification of an endogenous tryptic site by non-standard amino-acid substitutions.

Abstract: A power-tool cooling apparatus for a portable power tool comprises at least one cooling unit configured to generate a cooling fluid flow to cool a drive unit of the portable power tool, and at least one further cooling unit configured to generate a further cooling fluid flow. The at least one further cooling unit is designed to differ from the at least one cooling unit.

Abstract: A connection fitting (8) of a heat management module (1) of an internal combustion engine can be inserted into a receptacle hole (9) in a housing (2) of the heat management module. The aim is to be able to bias a sealing ring (16) of the nozzle against a rotary valve (3) using a compression spring element (13). The connection fitting is to be provided with a stop (24) that limits the longitudinal movement of the sealing ring in the direction of the rotary valve.

Abstract: A contact holder device for a hand-held power tool includes at least one main body that is disposed inside a housing unit of the hand-held power tool. The main body accommodates or fixes contact elements configured to transmit data signals and/or electrical energy. The main body has at least one disposition plane and at least one group of contact elements are disposed in the disposition plane. The main body has at least one further disposition plane and at least one further group of contact elements are disposed in the further disposition plane. The further disposition plane is disposed in an offset manner in relation to the disposition plane.