Implementation of a protein profiling platform developed as an academic-pharmaceutical industry collaborative effort

As much attention has devoted to the proteome research during the last few years, biomarker discovery has become an increasingly hot area, potentially enabling the development of new assays for diagnosis and prognosis of severe diseases. This is the field of research interest where efforts originating from both academic and industrial groups should jointly work on solutions. In this paper, we would like to demonstrate the fruitful combination of both research domains where the scientific crossroads sprout fresh ideas from the basic research domain and how these are refined and tethered to industrial standards. We will present an approach that is based on novel microfluidic devices, utilizing their benefits in processing small-volume samples. Our biomarker discovery strategy, built around this platform, involves optimized samples processing (based on SPE and sample enrichment) and fast MALDI-MS readout. The identification of novel biomarkers at low-abundance level has been achieved by the utilization of a miniaturized sample handling platform, which offers clean-up and enrichment of proteins in one step. Complete automation has been realized in the form of a unique robotic instrumentation that is able to extract and transfer 96 samples onto standard MALDI target plates with high throughput. The developed platform was operated with a 60 sample turnaround per hour allowing sensitivities in femtomol regions of medium- and low-abundant target proteins from clinical studies on samples of multiple sclerosis and gastroesophageal reflux disease. Several proteins have been identified as new biomarkers from cerebrospinal fluid and esophagus epithelial cells.     

Derivations, isomorphisms, and second cohomology of generalized Witt algebras

Generalized Witt algebras, over a field of characteristic , were defined by Kawamoto about 12 years ago. Using different notations from Kawamoto's, we give an essentially equivalent definition of generalized Witt algebras over , where the ingredients are an abelian group , a vector space over , and a map which is linear in the first variable and additive in the second one. In this paper, the derivations of any generalized Witt algebra
, with the right kernel of being , are explicitly described; the isomorphisms between any two simple generalized Witt algebras are completely determined; and the second cohomology group for any simple generalized Witt algebra is computed. The derivations, the automorphisms and the second cohomology groups of some special generalized Witt algebras have been studied by several other authors as indicated in the references.

     

Revisiting Consistency Conditions for Quantum States of Systems on Closed Timelike Curves: An Epistemic Perspective

There has been considerable recent interest in the consequences of closed timelike curves (CTCs) for the dynamics of quantum mechanical systems. A vast majority of research into this area makes use of the dynamical equations developed by Deutsch, which were developed from a consistency condition that assumes that mixed quantum states uniquely describe the physical state of a system. We criticize this choice of consistency condition from an epistemic perspective, i.e., a perspective in which the quantum state represents a state of knowledge about a system. We demonstrate that directly applying Deutsch’s condition when mixed states are treated as representing an observer’s knowledge of a system can conceal time travel paradoxes from the observer, rather than resolving them. To shed further light on the appropriate dynamics for quantum systems traversing CTCs, we make use of a toy epistemic theory with a strictly classical ontology due to Spekkens and show that, in contrast to the results of Deutsch, many of the traditional paradoxical effects of time travel are present.     

Temperature dependence of the penetration depth in Sr2RuO4: evidence for nodes in the gap function

We report measurements of the magnetic penetration depth in single crystals of Sr2RuO4 down to 0.04 K using a tunnel-diode based, self-inductive technique. We observe a power law temperature dependence below 0.8 K, with no sign of a second phase transition nor of a crossover predicted for a multiband superconductor. A power law dependence suggests that the gap function has nodes, inconsistent with candidate p-wave states. We argue that nonlocal effects, rather than impurity scattering, can explain the observed T2 dependence instead of the T-linear behavior expected for line nodes.     

The onset of coulomb explosions in polyatomic molecules

With the development of high intensity femtosecond lasers, the ionisation and dissociation dynamics of molecules has become an area of considerable interest. Using the technique of femtosecond laser mass spectrometry (FLMS), the molecules carbon disulphide, pyrimidine, toluene, cyclohexanone and benzaldehyde are studied with pulse widths of 50 fs in the near infrared (IR) wavelength region (790 nm). Results are presented and contrasted for laser beam intensities around 10(15) and 10(16) W cm(-2). For the lower intensities, the mass spectra yield dominant singly charged parent ions. Additionally, the appearance of doubly charged parent ions is evident for carbon disulphide, toluene and benzaldehyde with envelopes of doubly charged satellite species existing in these local regions. Carbon disulphide also reveals a small triply charged component. Such atomic-like features are thought to be a strong fingerprint of FLMS at these intensities. However, upon increasing the laser intensity to approximately 10(16) W cm(-2), parent ion dominance decreases and the appearance of multiply charged atomic species occurs, particularly carbon. This phenomenon has been attributed to Coulomb explosions in which the fast absorption of many photons may produce transient highly ionised parent species which can subsequently blow apart. Copyright 1999 John Wiley & Sons, Ltd.     

Uniform molecular analysis using femtosecond laser mass spectrometry

The potential of femtosecond laser time-of-flight mass spectrometry (FLMS) for uniform quantitative analysis of molecules has been investigated. Various samples of molecular gases and vapours have been studied, using ultra-fast ( approximately 50 fs) laser pulses with very high intensity (up to 1.6 x 10(16) Wcm(-2)) for non-resonant multiphoton ionisation/tunnel ionisation. Some of these molecules have high ionisation potentials, requiring up to ten photons for non-resonant ionisation. The relative sensitivity factors (RSF) have been determined as a function of the laser intensity and it has been demonstrated that for molecules with very different masses and ionisation potentials, uniform ionisation has been achieved at the highest laser intensities. Quantitative laser mass spectrometry of molecules is therefore a distinct possibility. Copyright 1999 John Wiley & Sons, Ltd.