Magnetic Resonance Force Microscopy with a One-Dimensional Resolution of 0.9 Nanometers.

Magnetic resonance force microscopy (MRFM) is a scanning probe technique capable of detecting MRI signals from nanoscale sample volumes, providing a paradigm-changing potential for structural biology and medical research. Thus far, however, experiments have not reached sufficient spatial resolution for retrieving meaningful structural information from samples. In this work, we report MRFM imaging scans demonstrating a resolution of 0.9 nm and a localization precision of 0.6 nm in one dimension. Our progress is enabled by an improved spin excitation protocol furnishing us with sharp spatial control on the MRFM imaging slice, combined with overall advances in instrument stability. From a modeling of the slice function, we expect that our arrangement supports spatial resolutions down to 0.3 nm given sufficient signal-to-noise ratio. Our experiment demonstrates the feasibility of subnanometer MRI and realizes an important milestone toward the three-dimensional imaging of macromolecular structures.

Nanoladder Cantilevers Made from Diamond and Silicon.

We present a "nanoladder" geometry that minimizes the mechanical dissipation of ultrasensitive cantilevers. A nanoladder cantilever consists of a lithographically patterned scaffold of rails and rungs with feature size ∼100 nm. Compared to a rectangular beam of the same dimensions, the mass and spring constant of a nanoladder are each reduced by roughly 2 orders of magnitude. We demonstrate a low force noise of 158-42+62 zN and 190-33+42 zN in a 1 Hz bandwidth for devices made from silicon and diamond, respectively, measured at temperatures between 100-150 mK. As opposed to bottom-up mechanical resonators like nanowires or nanotubes, nanoladder cantilevers can be batch-fabricated using standard lithography, which is a critical factor for applications in scanning force microscopy.

Permanent reduction of dissipation in nanomechanical Si resonators by chemical surface protection.

We report on mechanical dissipation measurements carried out on thin (∼100 nm), single-crystal silicon cantilevers with varying chemical surface termination. We find that the 1-2 nm-thick native oxide layer of silicon contributes about 85% to the friction of the mechanical resonance. We show that the mechanical friction is proportional to the thickness of the oxide layer and that it crucially depends on oxide formation conditions. We further demonstrate that chemical surface protection by nitridation, liquid-phase hydrosilylation, or gas-phase hydrosilylation can inhibit rapid oxide formation in air and results in a permanent improvement of the mechanical quality factor between three- and five-fold. This improvement extends to cryogenic temperatures. Presented recipes can be directly integrated with standard cleanroom processes and may be especially beneficial for ultrasensitive nanomechanical force- and mass sensors, including silicon cantilevers, membranes, or nanowires.

Biochemical compared to molecular diagnosis in acute intermittent porphyria.

The biochemical and the molecular diagnoses of an inherited porphyria require experience. False positive or negative screening tests and the low penetrance of the disease make a correct diagnosis difficult.The biochemical and the molecular procedures for the diagnosis of acute intermittent porphyria were applied to five unrelated patients suffering from acute intermittent porphyria. All patients were shown to be gene carriers of acute intermittent porphyria by both methods. The two different possibilities of the diagnosis corresponded well. In a family definitively identified by molecular diagnosis of one of the patients and his relatives, the patient's two children were asymptomatic. His son was shown to be a gene carrier of the father's deficiency by biochemical as well as molecular analysis, whereas his daughter was not affected by acute intermittent porphyria.

[Subacute thoracic pain]. / Subakuter Thoraxschmerz.

A 75-year old woman with essential hypertension presented two days after the onset of a sudden and strong thoracic pain. The pain did neither increase during breathing nor decrease after the ingestion of nitroglycerine, and could not be triggered by physical manipulation of the thoracic wall. Electrocardiogram showed a left bundle branch block, chest X-ray showed a widened upper mediastinum. Rupture/dissection of an aberrant right subclavian artery (a. lusoria) could be diagnosed by computed tomography. Successful implantation of an endovascular stent-graft was carried out. Evaluation of (sub)acute thoracic pain should include two-plane chest X-ray and, in case of a widened mediastinum, further investigation by computed tomography. In case of highly suspected rupture/dissection of an intrathoracic artery, a specific imaging procedure such as computed tomography is crucial.

Late oesophageal perforation after intraoperative transoesophageal echocardiography.

Serious haemodynamic instability occurred during emergency surgery for a perforated duodenal ulcer in a 72-year-old man with acute myocardial infarction. Intraoperative transoesophageal echocardiography was crucial for diagnosis of the location of myocardial infarction in the right ventricle and the subsequent haemodynamic management. Postoperatively, a thrombus in the right coronary artery was removed by coronary angiography. The patient's trachea was extubated on the fourth postoperative day. Another 4 days later a leak in the lower oesophagus was suspected because of pleural empyema, and verified. The patient's trachea had to be re-intubated and an oesophageal stent was inserted. The patient was discharged, fully recovered, 2 months after the operation.

Probability of occurrence of specific oligomers.

We improved an already existing formula for calculating the probability of occurrence of specific oligomers (Grob & Stüber, 1987) by taking into account unequal base distribution. This method identifies specific oligomers in a given sequence as candidates for biological signals.

SQUIRREL: Sequence QUery, Information Retrieval and REporting Library. A program package for analyzing signals in nucleic acid sequences for the VAX.

A computer tool is described for comparison, analysis and search of genetic signals. The method is based on sequence consensus matrices. It assumes that a genetic signal (such as a promoter, enhancer or whatever) is composed of several signal blocks separated from each other by variable distances. A set of programs is presented to perform the analysis. The result of such an analysis is a description of the investigated signal including matrices for each signal block, distances between each block and distribution of the values. Programs are provided to search for a signal using results from previous analysis. The method is able to align large sets of sequences within a few minutes and to check the quality of the alignment. An analysis of E.coli promoters is provided as an example.

A menu-shell for the GCG programs.

We provide a menu-driven integration of the genetic programs of the Genetics Computer Group (GCG). This allows in-experienced users a very simple access to all GCG programs regardless of the system environment. No modifications to the GCG package are necessary.

COOL--a VAX program for finding COmmon OLigomers in nucleic acid sequences. Thyroid hormone receptor sequences used as an example.

COOL is a program designed to find COmmon OLigomers in a number of nucleic acid sequences. The results of COOL serve as starting points in sequence analysis investigations as well as suggestions for polymerase chain reaction probes. As an example we analyzed thyroid hormone receptor genes and found two oligomers which are characteristic of almost all those genes.

Statistical analysis of nucleotide sequences.

In order to scan nucleic acid databases for potentially relevant but as yet unknown signals, we have developed an improved statistical model for pattern analysis of nucleic acid sequences by modifying previous methods based on Markov chains. We demonstrate the importance of selecting the appropriate parameters in order for the method to function at all. The model allows the simultaneous analysis of several short sequences with unequal base frequencies and Markov order k not equal to 0 as is usually the case in databases. As a test of these modifications, we show that in E. coli sequences there is a bias against palindromic hexamers which correspond to known restriction enzyme recognition sites.

Recognition of ill-defined signals in nucleic acid sequences.

A set of programs has been developed for the definition and handling of nucleic acid sequence consensus information. The sequences of known genetic control signals are combined in a matrix. The origins and positions of the signals are recorded. Old matrices can be updated dynamically: new signals are included and obsolete ones deleted. Matrices of several different types are computed optionally. Several of these matrices can be combined to find possible new signals. The use of matrices allows the exact quantification of signal qualities. The described programs are part of a program library named GENEXPERT. Application examples given are the search for tRNA genes and the search for promoters in the bacteriophage lambda genome.

Discrimination of phytochrome dependent light inducible from non-light inducible plant genes. Prediction of a common light-responsive element (LRE) in phytochrome dependent light inducible plant genes.

We aligned 14 5'-leading sequences of small subunit ribulose-1,5-bisphosphate carboxylase (rbcS) genes. A strong consensus sequence ("CCTTATCAT") was located directly upstream of the TATA-box. The occurrence of this motif in other light dependent phytochrome regulated plant genes led to the calculation of two consensus matrices. With these two matrices we are able to distinguish almost all known light induced plant genes which are phytochrome regulated from non-light induced plant genes indicating, that all these genes share a common light-responsive element (LRE). The results obtained by computer analysis are discussed with regard to experimental data.

GENEXPERT, a program system for nucleic acid sequence structural interpretation.

A program system for nucleic acid sequence analysis has been developed. The detection and prediction of secondary structures in nucleic acids have been especially emphasized. The system is able to handle most of the common problems found with nucleic acid sequencing like testing homologies, searching for reading frames and signals etc., but in addition it is able to locate and predict secondary structures. The predicted structures can either be printed on normal line printers or displayed on drawing devices like plotters or video screens. Another special feature is the data base-like handling of consensus sequence matrices by the programs DYCOM and EAGLE. Detailed descriptions of the programs have been published elsewhere (Stüber, 1985, 1986).

[Recurring tumors of the parotid gland with special reference to pleomorphic adenoma]. / Die Rezidivtumoren der Glandula parotis unter besonderer Berücksichtigung des pleomorphen Adenoms.

161 patients with parotid tumors seen between 1974 and 1980 are analyzed. A recurrence rate of 20% was found for both benign and malignant tumors. 76% of the recurrent tumors were judged to have been inadequately excised at the first operation. Pleomorphic adenomas had a recurrence rate of 25%. More than half these tumors exhibited multinodular patterns of recurrence. Therefore, a recurrent pleomorphic adenoma should not be reoperated upon for at least one year.