Identification of thymidine-5'-aldehyde at DNA strand breaks induced by neocarzinostatin chromophore

Snake venom phosphodiesterase or endonuclease S1 digestion of neocarzinostatin chromophore-treated DNA, labeled in its thymidine residues, liberates an unusual labeled nucleoside from the 5′ end of a drug-induced break. This substance, isolated by reverse-phase HPLC, possesses carbons from both the thymine and the deoxyribose moieties of thymidine in the DNA but, unlike thymidine, is readily degraded at pH 12 to thymine and a sugar fragment. The altered nucleoside was shown to contain a carbonyl group by its reduction with NaBH₄ to form a substance that has the chromatographic properties of thymidine and by its reaction with various hydrazines to form the respective hydrazone derivatives; the carbonyl exists as the 5′ aldehyde as shown by its mild chemical oxidation to the carboxylic acid with simultaneous loss of the 5′ ³H. Mass spectral analysis showed a fragmentation pattern compatible with the structure thymidine-5′-aldehyde. These data indicate that the nonprotein chromophore of neocarzinostatin, in the presence of a reducing substance (2-mercaptoethanol) and molecular oxygen, selectively oxidizes the 5′ carbon of nucleosides in DNA to the aldehyde, resulting in a strand break and a DNA fragment bearing nucleoside-5′-aldehyde at its 5′ end.     

Real time ultrasonic imaging with a hand-held scanner Part I—Technical description

Full integration of all necessary components of a real time linear array scanner into a small hand-held imaging device is possible. The instrument widely expands the clinical application of present ultrasound techniques. The total weight of the prototype instrument is 1.5 kg and battery power allows approximately 1.5 hr operation. The principles and design considerations are described.     

Learning in higher order Boltzmann machines using linear response.

We introduce an efficient method for learning and inference in higher order Boltzmann machines. The method is based on mean field theory with the linear response correction. We compute the correlations using the exact and the approximated method for a fully connected third order network of ten neurons. In addition, we compare the results of the exact and approximate learning algorithm. Finally we use the presented method to solve the shifter problem. We conclude that the linear response approximation gives good results as long as the couplings are not too large.     

Roles of chromophore and apo-protein in neocarzinostatin action.

The methanol-extractable, nonprotein chromophore of the antitumor, protein antibiotic neocarzinostatin (NCS) has at least the full activity of the parent compound in inhibiting DNA synthesis and growth of HeLa cells and in causing DNA strand breaks in vivo and in vitro. In vitro DNA strand scission by the chromophore is markedly stimulated by 2-mercaptoethanol and is inhibited by guanidine hydrochloride and alpha-tocopherol. By high-pressure liquid chromatography, this activity has been localized to fractions eluting at greater than 90% methanol and having fluorescence emission at 420 nm (excitation at 340 nm). The apo-protein of NCS is inactive by itself but complexes with the chromophore so as to regulate its availability during the in vitro reaction. In DNA strand scission the chromophore acts rapidly at both 0 and 37 degrees C, whereas native and reconstituted NCS are inactive at 0 degrees C and slowly active at 37 degrees C. Complex formation with apo-NCS stabilizes the chromophore. Reconstitution of NCS (pI 3.3) from chromophore and apo-protein (pI 3.2) was shown by both activity studies and isoelectric focusing on polyacrylamide gels. "Pre-NCS," the biosynthetic precursor of NCS, is identical to apo-NCS in amino acid composition, spectral properties, isoelectric focusing on polyacryl-amide gels, and ability to complex with isolated chromophore to form material with all the properties of native NCS.     

On the use of interaction error potentials for adaptive brain computer interfaces

We propose an adaptive classification method for the Brain Computer Interfaces (BCI) which uses Interaction Error Potentials (IErrPs) as a reinforcement signal and adapts the classifier parameters when an error is detected. We analyze the quality of the proposed approach in relation to the misclassification of the IErrPs. In addition we compare static versus adaptive classification performance using artificial and MEG data. We show that the proposed adaptive framework significantly improves the static classification methods.     

Delirium in neurosurgery: a systematic review and meta-analysis

Delirium is a frequent occurring complication in surgical patients. Nevertheless, a scientific work-up of the clinical relevance of delirium after intracranial surgery is lacking. We conducted a systematic review (CRD42020166656) to evaluate the current diagnostic work-up, incidence, risk factors and health outcomes of delirium in this population. Five databases (Embase, Medline, Web of Science, PsycINFO, Cochrane Central) were searched from inception through March 31st, 2021. Twenty-four studies (5589 patients) were included for qualitative analysis and twenty-one studies for quantitative analysis (5083 patients). Validated delirium screening tools were used in 70% of the studies, consisting of the Confusion Assessment Method (intensive care unit) (45%), Delirium Observation Screening Scale (5%), Intensive Care Delirium Screening Checklist (10%), Neelon and Champagne Confusion Scale (5%) and Nursing Delirium Screening Scale (5%). Incidence of post-operative delirium after intracranial surgery was 19%, ranging from 12 to 26% caused by variation in clinical features and delirium assessment methods. Meta-regression for age and gender did not show a correlation with delirium. We present an overview of risk factors and health outcomes associated with the onset of delirium. Our review highlights the need of future research on delirium in neurosurgery, which should focus on optimizing diagnosis and assessing prognostic significance and management.