Mass spectrometric immunoassay and MRM as targeted MS-based quantitative approaches in biomarker development: Potential applications to cardiovascular disease and diabetes

Type 2 diabetes mellitus (T2DM) is an important risk factor for cardiovascular disease (CVD)—the leading cause of death in the United States. Yet not all subjects with T2DM are at equal risk for CVD complications; the challenge lies in identifying those at greatest risk. Therapies directed toward treating conventional risk factors have failed to significantly reduce this residual risk in T2DM patients. Thus newer targets and markers are needed for the development and testing of novel therapies. Herein we review two complementary MS-based approaches—mass spectrometric immunoassay (MSIA) and MS/MS as MRM—for the analysis of plasma proteins and PTMs of relevance to T2DM and CVD. Together, these complementary approaches allow for high-throughput monitoring of many PTMs and the absolute quantification of proteins near the low picomolar range. In this review article, we discuss the clinical relevance of the high density lipoprotein (HDL) proteome and Apolipoprotein A-I PTMs to T2DM and CVD as well as provide illustrative MSIA and MRM data on HDL proteins from T2DM patients to provide examples of how these MS approaches can be applied to gain new insight regarding cardiovascular risk factors. Also discussed are the reproducibility, interpretation, and limitations of each technique with an emphasis on their capacities to facilitate the translation of new biomarkers into clinical practice.     

A Trustworthy Proof Checker

Proof-carrying code (PCC) and other applications in computer security require machine-checkable proofs of properties of machine-language programs. The main advantage of the PCC approach is that the amount of code that must be explicitly trusted is very small: it consists of the logic in which predicates and proofs are expressed, the safety predicate, and the proof checker. We have built a minimal proof checker, and we explain its design principles and the representation issues of the logic, safety predicate, and safety proofs. We show that the trusted computing base (TCB) in such a system can indeed be very small. In our current system the TCB is less than 2,700 lines of code (an order of magnitude smaller even than other PCC systems), which adds to our confidence of its correctness.     

Matched asymptotic expansions for bent and twisted rods: applications for cable and pipeline laying

The geometrically exact theory of linear elastic rods is used to formulate the general three-dimensional problem of a twisted, clamped rod hanging under gravity and subject to buoyancy forces from a fluid. The resulting boundary-value problem is solved by the method of matched asymptotic expansions. The truncated analytical solution is compared with results obtained from a numerical scheme and shows good agreement. The method is used to consider the near-catenary application of a clamped pipeline. Key words: rod theory, matched asymptotic expansions, boundary layers, catenary, heavy cables, pipelines, buoyancy forces     

The Auer and Herzog collections: Two encyclopaedic projects in Switzerland

Abstract

‘Made in Switzerland. The Photography Collections of the Swiss Confederation’ was an exhibition organized by the Swiss Federal Office of Culture and hosted by the Musee de l'Elysee in Lausanne in 1997. The exhibition officially confIrmed that the Swiss are at last beginning to recognize the value of their national photographic heritage. Official efforts concerning the conservation of photographs have until recently consisted of the preservation of architectural documents by the Federal Archive for the Protection of Monuments in Bern and of the rather limited activities of the Swiss Foundation of Photography, located in Zurich since 1971, which has primarily focused on professional reportage. Two private collectors, however, have been discreetly active for over three decades amassing thousands of photographs, albums, cameras, and books on photography, thus safeguarding material that might have been lost or destroyed due to the general lack of interest shown by public institutions. Michele and Michel Auer, two photography encyclopaedists living in Hermance on Lake Geneva, and Ruth and Peter Herzog in Basle have assembled the two largest private photography collections in Switzerland. But whereas collecting is an extension of the professional work of the Auers, Ruth Herzog-Wyss, a book dealer, and Peter Herzog, a lawyer and art expert, are amateur collectors.     

Intellectual performance in multi-infarct dementia and Alzheimer''s disease a replication study

A comparative study was conducted to evaluate the efficacy of a metal or flexible plastic 8 mm cannula for artificial abortion by vacuum aspiration for patients at six to 10 weeks' gestation. Complication rates, amounts of retained tissue (obtained with a curette check), frequencies of cannula obstructions and procedure times were used as criteria for determining the efficacy of the two types of cannulae. Two physicians participated in the study: one was responsible for the preliminary examination and performance of the abortion, and the other physician, who was kept unaware of the type of cannula used, was responsible for patient care after completions of the abortion to the time of the follow-up visit. Paracervical block anesthesia was used in all cases. Differences in complication rates (controlled for gestational age) between groups of subjects aborted with either the metal or flexible plastic cannula were not significantly different (p less than .05). For both patient groups shock was the most frequently reported immediate complication (2.7% in the metal cannula group, 4,7% in the flexible plastic cannula group), and leukorrhea was the most frequently reported complication at the time of follow-up (3.3% metal, 5.3% flexible plastic). Amounts of retained tissue and frequency of cannulae obstruction were similar for both groups. Procedure times were also similar for both groups (means of 5.7 minutes and 5.5 minutes, respectively, for procedures performed with the metal and flexible plastic cannulae).     

The systemic arterial pattern of the guinea pig: the pelvis and pelvic limb

The changes of heart rate in response to i.v. administration of methylatropine (0.5 mg/kg) and/or propranolol (2 mg/Kg) or practolol (2.5 mg/Kg) were studied in conscious trained dogs. Cholinergic blockade alone or combined blockade of sympathetic and parasympathetic effector systems resulted in cardiac acceleration. Conversely, beta-adrenoceptor antagonism with either propranolol or practolol reduced heart rate. The data were analysed by means of a new method, whereby the heart (HRN) of the dog is considered to be the product of the intrinsic heart rate (HR0) and 3 further factors: HRN-HR0 times S times V times W (Multiplicative model). 2 of these factors represent the tonic sympathetic (S) and parasympathetic (V) influences, whereas the third (W) represents the sympathetic-parasympathetic interaction. This type of analysis reveals that W was approximately 1, i.e., the sympathetic-parasympathetic interaction did not play any significant role in determining the heart rate of conscious resting dogs (HRN = HRO-S-V-W = HRO-S-V). The change of heart rate due to the action of parasympathetic system (-53% of the intrinsic heart rate) was more important than the change caused by the action of the sympathetic system (26% of the intrinsic heart rate).