On-chip laser-induced DNA dehybridization.

Detection of pathogens and relevant genetic markers using their nucleic acid signatures is extremely common due to the inherent specificity genomic sequences provide. One approach for assaying a sample simultaneously for many different targets is the DNA microarray, which consists of several million short nucleic acid sequences (probes) bound to an inexpensive transparent substrate. Typically, complex samples hybridize to the microarray and the pattern of fluorescing probes on the microarray's surface identifies the detected targets. In the case of evolving or newly emergent organisms, a hybridization pattern can occur that differs from any previously known sources. When this happens it can be useful to recover the hybridized DNA from the binding locations of interest for sequencing. Here we present the novel utilization of a focused Infrared (IR) laser to heat user-selected spots on the DNA microarray surface, causing only localized dehybridization and recovery of the desired DNA into an elution buffer where it is available for subsequent amplification or sequencing. The introduction of a focused dehybridization method for spots of interest suppresses the amount of background DNA to be analyzed from downstream processes, and should reduce subsequent sequence assembly errors. This technique could also be applied to high-density protein microarrays where the desire to locally heat spots for release of bound molecules is desired.

Subthalamic deep brain stimulation and impulse control in Parkinson's disease.

BACKGROUND AND PURPOSE: Experimental studies suggest that deep brain stimulation (DBS) of the subthalamic nucleus (STN) induces impulsivity in patients with Parkinson's disease (PD). The purpose of this study was to assess various measures of impulse control in PD patients with STN DBS in comparison to patients receiving medical therapy. METHODS: In a cross-sectional evaluation, 53 consecutively eligible patients were assessed for impulsivity with the Barratt Impulsiveness Scale, for impulse control disorders (ICDs) using the Minnesota Impulsive Disorders Interview, and for obsessive-compulsive symptoms using the Maudsley Obsessional-Compulsive Inventory. RESULTS: Independent samples t-tests revealed that compulsivity scores were not different between DBS patients and patients without DBS. However, impulsivity scores were significantly higher in DBS patients. Additionally, ICDs were observed in 3 of 16 (19%) DBS patients and in 3 of 37 (8%) medically treated patients. No association was found between the use of dopamine agonists and impulsivity in DBS patients. CONCLUSIONS: Our data suggest that screening for impulsivity and ICDs should be performed prior to DBS, and that patients should be monitored for these problems during follow-up. Prospective trials are needed to confirm the findings of this exploratory study and to elucidate the reasons of a possible induction of impulsivity by STN DBS.

Irreversible enzyme inhibitors. 202. Candidate active-site-directed irreversible inhibitors of 5-fluoro-2'-deoxyuridine phosphorylase from Walker 256 rat tumor derived from 1-benzyl-5-(3-ethoxybenzyl)uracil.

Six candidate irreversible inhibitors of uridine--deoxyuridine phosphorylase (EC 2.4.2.3) from Walker 256 rat tumor were synthesized. These compounds connect a terminal sulfonyl fluoride group to the 1-benzyl moiety of 1-benzyl-5-(3-ethoxybenzyl)uracil (9). Although none of the compounds were irreversible inhibitors, the four 3-[(fluorosulfonyl)benzamido] analogues (14-17) of 9 were good reversible inhibitors of the enzyme which were complexed from 125- to 360-fold better than the substrate, 5-fluoro-2'-deoxyuridine.

Mental state and other prognostic factors in femoral fractures of the elderly.

Fifty elderly patients with fractured femurs were followed up for six months. A hospital stay of less than 28 days and a good prefracture mental state were such important favourable prognostic factors that their absence made the outlook poor and carried clear implications concerning management.

The patient's greatest hazard.

To reduce the patient's hazard in the dental office, the dentist must take a medical history, perform a limited medical examination, order and interpret laboratory tests when indicated, initiate medical consultation when necessary, and evaluate the data obtained in order to make appropriate treatment modifications for high risk patients. The current status of health which our population enjoys must not be confused with a status of robustness. An apparently well patient may be in great jeopardy while you are delivering the most skillful dental care unless adequate precautions are taken.

Irreversible enzyme inhibitors. 200. Active-site-directed inhibitors of deoxycytidine kinase.

Forty-three pyrimidine derivatives, mainly containing the 4-aminopyrimidine system, have been prepared and evaluated as inhibitors of deoxycytidine kinase. The most effective inhibitors were 2-alkylthio-4-aminopyrimidines and 1-alky-1-cytosines. The best inhibitors in both groups were those with large alkyl substituents, which indicate that hydrophobic bonding is occurring, possibly in the same area adjacent to the active site.

Irreversible enzyme inhibitors. Inhibitors of guinea pig complement derived by quaternization of substituted pyridines with benzyl halides.

A series of 83 compounds derived from hydrocarbon-substituted pyridines by quaternization with PhCH2Br usually containing a 2-SO2F or 6-Cl-2-SO2F group was synthesized and evaluated as inhibitors of guinea pig complement and in most cases its C1 component. The most active compounds were 3-(4-phenylphenylbutyl)-N-(6-choro-2-fluorosulfonylbenzyl) pyridinium bromide (43) and 3-(4-phenylphenylbutyl)-N-(2-fluorosulfonylbenzyl) pyridinium bromide (44), each showing 50% inhibition at 7.8 muM. The most effective irreversible inhibitor of the C1 component was N-(6-chloro-2-fluorosulfonylbenzyl)-5,6-benzoquinolinium bromide (87), which showed 50% inhibition at 4 muM.

Scan line filters for optical spectral analysis.

A class of filters is studied for applications in optical spectrum analyzers. The output device of the analyzer is a masked vidicon. Consequently the design criteria differ from those for filters commonly used in digital data processing, radar antenna shading, and conventional apodization. It is shown that crosstalk or interlocus interference can be reduced for practical geometries to a level about 20-30 dB lower than that of an unshaded aperture.