Biochemical basis of 5-aminolaevulinic acid-induced protoporphyrin IX accumulation: a study in patients with (pre)malignant lesions of the oesophagus.

Administration of 5-aminolaevulinic acid (ALA) leads to porphyrin accumulation in malignant and premalignant tissues, and ALA is used as a prodrug in photodynamic therapy (PDT). To understand the mechanism of porphyrin accumulation after the administration of ALA and to investigate whether ALA-induced protoporphyrin IX might be a suitable photosensitizer in Barrett's oesophagus and adenocarcinoma, we determined the activities of porphobilinogen deaminase (PBG-D) and ferrochelatase (FC) in various malignant and premalignant as well as in normal tissues of the human oesophagus. A PDT power index for ALA-induced porphyrin accumulation, the ratio of PBG-D to FC normalized for the normal squamous epithelium of the oesophagus, was calculated to evaluate intertissue variation in the ability to accumulate porphyrins. In malignant and premalignant tissue a twofold increased PBG-D activity and a marginally increased FC activity was seen compared with normal squamous epithelium. A significantly increased PDT power index in Barrett's epithelium and adenocarcinoma was found. Our results suggest that, after the administration of ALA, porphyrins will accumulate in a greater amount in Barrett's epithelium and adenocarcinoma of the oesophagus because of an imbalance between PBG-D and FC activities. The PDT power index here defined might be a useful indicative parameter for predicting the susceptibility of these tissues to ALA-PDT

Porphyrin biosynthesis in human Barrett's oesophagus and adenocarcinoma after ingestion of 5-aminolaevulinic acid

5-Aminolaevulinic acid (ALA)-induced porphyrin biosynthesis, which is used for ALA-based photodynamic therapy (ALA-PDT), was studied in tissues of 10 patients with Barrett’s oesophagus (BE) and adenocarcinoma of the oesophagus (AC) undergoing oesophagectomy at a mean time interval of 6.7 h after the ingestion of ALA (60 mg kg–1). In BE, AC, squamous epithelium (SQ) and gastric cardia, the activities of the haem biosynthetic enzymes porphobilinogen deaminase (PBG-D) and ferrochelatase (FC) and the PDT power index – the ratio between PBG-D and FC in BE and AC in comparison with SQ – were determined before ALA ingestion. Following ALA administration, ALA, porphobilinogen, uroporphyrin I and PPIX were determined in tissues and plasma. The PDT power index did not predict the level of intracellular accumulation of PPIX found at 6.7 h. In BE, there was no selectivity of PPIX accumulation compared to SQ, whereas in half of patients with AC selectivity was found. Higher haem biosynthetic enzyme activities (i.e. PBG-D) and lower PPIX precursor concentrations were found in BE and AC compared to SQ. It is therefore possible that PPIX levels will peak at earlier time intervals in BE and AC compared to SQ. © 2000 Cancer Research Campaig

Heights of pre-special points of Shimura varieties

Let s be a special point on a Shimura variety, and x a pre-image of s in a fixed fundamental set of the associated Hermitian symmetric domain. We prove that the height of x is polynomially bounded with respect to the discriminant of the centre of the endomorphism ring of the corresponding ZZ -Hodge structure. Our bound is the final step needed to complete a proof of the André–Oort conjecture under the conjectural lower bounds for the sizes of Galois orbits of special points, using a strategy of Pila and Zannier

Key Rotation for Authenticated Encryption

A common requirement in practice is to periodically rotate the keys used to encrypt stored data. Systems used by Amazon and Google do so using a hybrid encryption technique which is eminently practical but has questionable security in the face of key compromises and does not provide full key rotation. Meanwhile, symmetric updatable encryption schemes (introduced by Boneh et al. CRYPTO 2013) support full key rotation without performing decryption: ciphertexts created under one key can be rotated to ciphertexts created under a different key with the help of a re-encryption token. By design, the tokens do not leak information about keys or plaintexts and so can be given to storage providers without compromising security. But the prior work of Boneh et al. addresses relatively weak confidentiality goals and does not consider integrity at all. Moreover, as we show, a subtle issue with their concrete scheme obviates a security proof even for confidentiality against passive attacks. This paper presents a systematic study of updatable Authenticated Encryption (AE). We provide a set of security notions that strengthen those in prior work. These notions enable us to tease out real-world security requirements of different strengths and build schemes that satisfy them efficiently. We show that the hybrid approach currently used in industry achieves relatively weak forms of confidentiality and integrity, but can be modified at low cost to meet our stronger confidentiality and integrity goals. This leads to a practical scheme that has negligible overhead beyond conventional AE. We then introduce re-encryption indistinguishability, a security notion that formally captures the idea of fully refreshing keys upon rotation. We show how to repair the scheme of Boneh et al., attaining our stronger confidentiality notion. We also show how to extend the scheme to provide integrity, and we prove that it meets our re- encryption indistinguishability notion. Finally, we discuss how to instantiate our scheme efficiently using off-the-shelf cryptographic components (AE, hashing, elliptic curves). We report on the performance of a prototype implementation, showing that fully secure key rotations can be performed at a throughput of approximately 116 kB/s

Three-dimensional bone kinematics in an anterior laxity test of the ankle joint

Questions addressed in this in-vitro study are (1) what are the actual three-dimensional kinematics of talus and calcaneus during an anterior drawer test as performed with the quasi-static anterior ankle tester (QAAT) (2) does laxity measurement with the QAAT represent the true anterior translation of talus relative to the tibia?. Simultaneous measurements were made with the QAAT and a three-dimensional kinematics analysis system in five specimens. The three-dimensional translations and rotations on three axes were analysed at 25, 50 and 100 N of applied anterior load, with increased ligament damage. For four out of five remaining specimens, anterior translation values of talus and calcaneus and values as measured with the QAAT show a significant increase with growing ligament damage and with higher loads. Skeletal motions of talus and calcaneus show great similarity in three different motion axes, with increased ligament damage and at any given load. Skeletal translations and rotations of talus and calcaneus show great similarity during an anterior drawer movement of the ankle joint. Anterior skeletal translation of the talus and calcaneus show fair correlation with the anterior displacements measurements of the QAAT. These QAAT measurements show an overestimation of the laxity value by more than 200% irrespective of the load applied. © Springer-Verlag 2007

The Relationship Between Knee Motion and Articular Surface Geometry

No abstract