Erythrocytes as Carriers of Therapeutic Enzymes.

Therapeutic enzymes are administered for the treatment of a wide variety of diseases. They exert their effects through binding with a high affinity and specificity to disease-causing substrates to catalyze their conversion to a non-noxious product, to induce an advantageous physiological change. However, the metabolic and clinical efficacies of parenterally or intramuscularly administered therapeutic enzymes are very often limited by short circulatory half-lives and hypersensitive and immunogenic reactions. Over the past five decades, the erythrocyte carrier has been extensively studied as a strategy for overcoming these limitations and increasing therapeutic efficacy. This review examines the rationale for the different therapeutic strategies that have been applied to erythrocyte-mediated enzyme therapy. These strategies include their application as circulating bioreactors, targeting the monocyte-macrophage system, the coupling of enzymes to the surface of the erythrocyte and the engineering of CD34+ hematopoietic precursor cells for the expression of therapeutic enzymes. An overview of the diverse biomedical applications for which they have been investigated is also provided, including the detoxification of exogenous chemicals, thrombolytic therapy, enzyme replacement therapy for metabolic diseases and antitumor therapy

Should insurance risk avoidance be reformed and would reform be of a right of equitable rescission or a right sui generis?

This article explores the distinction between the alternative explanations for the remedy of insurance risk avoidance in the event of breach of the duty of utmost good faith. It asks whether the remedy is an avoidance of a void contract, or a rescission of a voidable contract. The article then considers the general significance of that distinction to the capacity of a party to exercise its primary right of avoidance, and to the secondary rights of the contracting parties - arising in consequence of the avoidance - to prevent unjust enrichment or achieve restitution. Before considering the potential for - and the desirability of - further reform in the area, the article evaluates the importance of the legal characterisation of insurance risk avoidance in the particular context of insurance contracts affording indemnity to multiple insured parties

Work

Job postings that explicitly encourage “people with migration backgrounds” or those who “experience discrimination” to apply, were a good start once. But they do not solve the problem. Sure, an injustice is being identified here that is imperative to counteract. Unless rules like quotas are established, however, such postings ultimately peter out as a merely symbolic gesture. In the end, it is not the well-intended statement that counts, but who is being hired. And who isn’t

Complexities associated with expression of Epstein-Barr virus (EBV) lytic origins of DNA replication.

EBV has two lytic origins (oriLyt) of DNA replication lying at divergent sites on the viral genome within a duplicated sequence (DS). The latter contains potential hairpin loops, ‘hinge’ elements and the promoters for transcripts from viral genes BHLF1 and LF3. These genes themselves consist largely of 125 and 102 bp repetitive sequences, respectively, and encode basic proteins. We have examined these genomic regions in detail in attempts to understand why lytic replication—necessary for virus survival—is so inefficient, and to identify controlling elements. Our studies uncovered a diverse family of promoters (P) for BHLF1 and LF3, only one pair of which (P1) proved sensitive to chemical inducing agents. The others (P2–P3/4), abutting the replication ‘core’ origin elements in DS and extending into 50-unique sequences, may play roles in the maintenance of viral latency. We further identified a family of overlapping small complementary-strand RNAs that transverse the replication ‘core’ origin elements in a manner suggesting a role for them as ‘antisense’ species and/or DNA replication primers. Our data are discussed in terms of alternative lytic replication models. We suggest our findings might prove useful in seeking better control over viral lytic replication and devising strategies for therapy

Evaluation of touch trigger probe measurement uncertainty using FEA

Evaluation of measurement uncertainty is an essential subject in dimensional measurement. It has also become a dominant issue in coordinate measuring machine (CMM) even though its machine performance has been well accepted by many users. CMM probes, especially touch trigger probes which are commonly used, have been acknowledged as a key error source, largely due to pre-travel variations. The probe errors result in large measurement uncertainty in CMM measurement. Various methods have been introduced to estimate measurement uncertainty, but they tend to be time consuming and necessarily require a large amount of experimental data for analyzing the uncertainty. This paper presents the method of evaluation of CMM probe uncertainty using FEA modeling. It is started with the investigation of the behavior of probe by recording stylus displacement with vary triggering force. Then, those displacement results will be analyzed with sensitivity analysis technique to estimate the uncertainty of recorded results

Acoustic emission and vibration for tool wear monitoring in single-point

This paper proposes an implementation of calibrated acoustic emission (AE) and vibration techniques to monitor progressive stages of flank wear on carbide tool tips. Three cutting conditions were used on workpiece material, type EN24T, in turning operation. The root-mean-square value of AE (AErms) and the coherence function between the acceleration signals at the tool tip in the tangential and feed directions was studied. Three features were identified to be sensitive to tool wear: AErms, coherence function in the frequency ranges 2.5-5.5 kHz and 18-25 kHz. Belief network based on Bayes’ rule was used to integrate information in order to recognise the occurrence of worn tool. The three features obtained from the three cutting conditions and machine time were used to train the network. The set of feature vectors for worn tools was divided into two equal sub-sets: one to train the network and the other to test it. The AErms in term of AE pressure equivalent was used to train and test the net work to validate the calibrated acoustic. The overall success rate of the network in detecting a worn tool was high with low error rate

Hydrocarbon emissions from a modern commercial airliner

We report selected carbon species emission indices (EIs) for a Rolls Royce RB211-535-E4 turbofan engine that were acquired during the NASA EXperiment to Characterize Aircraft Volatile Aerosol and Trace-species Emissions (EXCAVATE). Conducted during winter 2002, the mission focused upon characterizing the exhaust constituents of the NASA Boeing 757 aircraft during ground-based operation. Carbon species concentrations were determined by chromatographic analyses of whole air samples collected 10 m behind the engine exit plane as engine power was varied from ground idle to about 60% of maximum rated thrust. Ambient air samples were also collected and analyzed to facilitate correction of calculated EIs for background concentrations. Results are consistent with previous observations and indicate that, on a relative basis, turbine engines emit considerable amounts of light hydrocarbon species at idle, but significantly lesser amounts at higher engine powers. © 2005 Elsevier Ltd. All rights reserved

The EC REACH Regulation and contractual supply obligations

REACH, as an EC legislative instrument in the form of a community regulation, is directly applicable in the national domestic laws of each of the 30 states in the European Economic Area (EEA). REACH now takes effect within the context of the Treaty on the Functioning of the European Union (TFEU) and the Treaty on European Union (TEU), both of which entered into force under the Treaty of Lisbon on December 1, 2009 and replace, as from that date, the prior governing Treaties of the European Union (EU). REACH prohibits the placing of registrable substances, on their own, or in preparations or articles, on the market in the EEA unless they have been registered and, when required, their use authorised in accordance with REACH. It also places obligations on sellers and buyers of such substances (or of preparations--and in certain circumstances even articles containing them) to pass product, risk and use information both up and down the supply chain and also to the European Chemicals Agency (ECHA), which is effectively responsible for managing the registration, authorisation and restriction process across the EEA and for co-ordinating the implementation of REACH by the EEA states. REACH has the capacity to have direct effects on the rights and duties of parties buying and selling within, and into, the EEA