Abstract: A method for a gradual credential disablement is provided. The method includes receiving, at data processing hardware, a request for access to a resource. The request includes a request authenticator. The method also includes comparing, by the data processing hardware, the request authenticator against a security credential associated with the resource. The method further includes determining, by the data processing hardware, whether the request authenticator satisfies the security credential. When the request authenticator satisfies the security credential, the method includes granting or denying, by the data processing hardware, access to the resource based on a request failure rate associated with the security credential.

Abstract: A method for a gradual credential disablement is provided. The method includes receiving, at data processing hardware, a request for access to a resource. The request includes a request authenticator. The method also includes comparing, by the data processing hardware, the request authenticator against a security credential associated with the resource. The method further includes determining, by the data processing hardware, whether the request authenticator satisfies the security credential. When the request authenticator satisfies the security credential, the method includes granting or denying, by the data processing hardware, access to the resource based on a request failure rate associated with the security credential.

Abstract: A method for a gradual credential disablement is provided. The method includes receiving, at data processing hardware, a request for access to a resource. The request includes a request authenticator. The method also includes comparing, by the data processing hardware, the request authenticator against a security credential associated with the resource. The method further includes determining, by the data processing hardware, whether the request authenticator satisfies the security credential. When the request authenticator satisfies the security credential, the method includes granting or denying, by the data processing hardware, access to the resource based on a request failure rate associated with the security credential.

Abstract: A method for a gradual credential disablement is provided. The method includes receiving, at data processing hardware, a request for access to a resource. The request includes a request authenticator. The method also includes comparing, by the data processing hardware, the request authenticator against a security credential associated with the resource. The method further includes determining, by the data processing hardware, whether the request authenticator satisfies the security credential. When the request authenticator satisfies the security credential, the method includes granting or denying, by the data processing hardware, access to the resource based on a request failure rate associated with the security credential.

Abstract: Novel compounds of Formula (I) or pharmaceutically acceptable salts, prodrugs and biologically active metabolites thereof of Formula (I) wherein the substituents are as defined herein, which are useful as therapeutic agents.

Abstract: A compound or pharmaceutically acceptable salts thereof of Formula (I) wherein the substituents are as defined herein, which are useful as kinase inhibitors.

Abstract: Disclosed are compounds of formula(I): wherein Ar1, Ar2, R1, R2, R3, R4 and Xa are defined herein. The compounds of the invention inhibit Itk kinase and are therefore useful for treating diseases and pathological conditions involving inflammation, immunological disorders and allergic disorders. Also disclosed are processes for preparing these compounds and to pharmaceutical compositions comprising these compounds.

Abstract: Disclosed are substituted benzimidazole compounds of formula (I): wherein R1, R2, R3, R4 and Xa are defined herein. The compounds of the invention inhibit Itk kinase and are therefore useful for treating diseases and pathological conditions involving inflammation, immunological disorders and allergic disorders. Also disclosed are processes for preparing these compounds and to pharmaceutical compositions comprising these compounds.

Abstract: Disclosed are ketone substituted benzimidazole compounds of formula(I): wherein R1, R2, R3, R4 and Xa are defined herein. The compounds of the invention inhibit Itk kinase and are therefore useful for treating diseases and pathological conditions involving inflammation, immunological disorders and allergic disorders. Also disclosed are processes for preparing these compounds and to pharmaceutical compositions comprising these compounds.

Abstract: An catalytic converter is integrated with a flexible endcone to form an assembly. The assembly comprises a catalytic converter with a flexible endcone integrated connected to one end of the catalytic converter, which is optionally attached to a mounting flange or exhaust pipe. The endcone comprises a flexible bellow containing a plurality of undulating ribs. The flexible bellow is secured to an end of the catalytic converter at one or more interface points along the periphery of the flexible endcone assembly.

Abstract: Disclosed is an apparatus for automated synthesis containing a shaker deck with a plurality of reaction blocks containing a plurality of reaction wells, an arm containing an array of extending units capable of actuating physical steps along a plurality of axes of each reaction block, each reaction block being situated on a turntable, each turntable being further capable of rotating the reaction block along a central axis. Also disclosed are methods of preparing a peptide, oligonucleotide an small molecules using the apparatus.

Abstract: This invention relates to process for asymmetrically producing enantiomerically pure .alpha.-cycloalkylalkyl substitututed methanamines from .alpha.-pinene. One key step of the process of this invention utilizes the oxidation product of .alpha.-pinene, hydroxy pinanone, as a chiral auxiliary to direct the stereoselective alkylation of the corresponding ketimine. This invention also relates to key intermediates useful in the processes referred to herein.

Abstract: The present invention provides paclitaxel derivatives of formula I ##STR1## and pharmaceutical compositions.

Abstract: The present invention provides paclitaxel derivatives of formula I ##STR1## in which R.sup.1 is --COR.sup.z, in which R.sup.z is RR.sup.o N--, RHN--, RO-- or R;R.sup.2 is C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, C.sub.3-6 cycloalkyl, or a radical of the formula --W--R.sup.x in which W is a bond, C.sub.2-6 alkenediyl, or --(CH.sub.2).sub.t --, in which t is one to six; and R.sup.x is naphthyl, phenyl, or heteroaryl, and furthermore R.sup.x can be optionally substituted with one to three same or different C.sub.1-6 alkyl, C.sub.1-6 alkoxy, halogen or --CF.sub.3 groups;R and R.sup.o are independently C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.3-6 cycloalkyl, C.sub.2-6 alkynyl, or phenyl, optionally substituted with one to three same or different C.sub.1-6 alkyl, C.sub.1-6 alkoxy, halogen or --CF.sub.3 groups.Also provided by this invention are pharmaceutical formulations (compositions) and a method of treating mammalian tumors with a compound of formula I.

Abstract: The present invention provides paclitaxel derivatives of formula I ##STR1## in which R.sup.1 is --COR.sup.z in which R.sup.Z is RO-- or R;R.sup.2 is C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, C.sub.3-6 cycloalkyl, or a radical of the formula --W--R.sup.x in which W is a bond, C.sub.2-6 alkenediyl, or --(CH.sub.2).sub.t --, in which t is one to six; and R.sup.x is naphthyl, phenyl, or heteroaryl, and furthermore R.sup.x can be optionally substituted with one to three same or different C.sub.1-6 alkyl, C.sub.1-6 alkoxy, halogen or --CF.sub.3 groups;R.sup.a is --OCOR, H, OH, --OR, --OSO.sub.2 R, --OCONR.sup.o R, --OCONHR, --OCOO(CH.sub.2).sub.t R, or --OCOOR;R.sup.b and R.sup.c are both hydroxy or together form a bond with the carbon atoms to which they are attached; andR and R.sup.o are independently C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.3-6 cycloalkyl, C.sub.2-6 alkynyl, or phenyl, optionally substituted with one to three same or different C.sub.1-6 alkyl, C.sub.1-6 alkoxy, halogen or --CF.sub.