Indirect Processing Research Articles

HSQC-1,n -ADEQUATE: a new approach to long-range 13 C13 C correlation by covariance processing

Long-range, two-dimensional heteronuclear shift correlation NMR methods play a pivotal role in the assembly of novel molecular structures. The well-established GHMBC method is a high-sensitivity mainstay technique, affording connectivity information via (n)J(CH) coupling pathways. Unfortunately, there is no simple way of determining the value of n and hence no way of differentiating two-bond from three- and occasionally four-bond correlations. Three-bond correlations, however, generally predominate. Recent work has shown that the unsymmetrical indirect covariance or generalized indirect covariance processing of multiplicity edited GHSQC and 1,1-ADEQUATE spectra provides high-sensitivity access to a (13)C-(13) C connectivity map in the form of an HSQC-1,1-ADEQUATE spectrum. Covariance processing of these data allows the 1,1-ADEQUATE connectivity information to be exploited with the inherent sensitivity of the GHSQC spectrum rather than the intrinsically lower sensitivity of the 1,1-ADEQUATE spectrum itself. Data acquisition times and/or sample size can be substantially reduced when covariance processing is to be employed. In an extension of that work, 1,n-ADEQUATE spectra can likewise be subjected to covariance processing to afford high-sensitivity access to the equivalent of (4)J(CH) GHMBC connectivity information. The method is illustrated using strychnine as a model compound.

Using indirect covariance processing for structure elucidation of small molecules in cases of spectral crowding

Indirect and unsymmetrical indirect covariance NMR provide powerful tools to compute and visualize correlation information by transforming component spectra into combined spectral data matrices. Sensitive component spectra such as TOCSY, HSQC and NOESY can be quickly converted into experimentally insensitive or time-consuming correlation spectra such as HSQC-NOESY. The comparison of illustrative series of spectra from four steroids, dexamethasone, testosterone, allylestrenol and tibolone, renders the effects of resonance overlap on the ease of interpretation visible. The compounds are selected such that signal overlap increases systematically in the proton and carbon domain. Spectra are defined as light, moderate and heavy signal overlap, based on signal density. The investigation suggests that moderate spectral congestion in either proton or carbon domain leads to a number of artifacts that does not hamper signal assignment but lowers the level of confidence on de novo structure elucidation. Since the number of correlations usually increases through covariance processing, component spectra with severe spectral congestion in both dimensions are not suitable for covariance processing and the resulting spectra do not support structure confirmation or structure elucidation. The calculated spectra are compared with the corresponding experimental spectra with respect to their application in structure elucidation laboratory environments.

Brain activation during direct and indirect processing of positive and negative words

The effects of task conditions on brain activation to emotional stimuli are poorly understood. In this event-related fMRI study, brain activation to negative and positive words (matched for arousal) and neutral words was investigated under two task conditions. Subjects either had to attend to the emotional meaning (direct task) or to non-emotional features of the words (indirect task). Regardless of task, positive vs. negative words led to increased activation in the ventral medial prefrontal cortex, while negative vs. positive words induced increased activation of the insula. Compared to neutral words, all emotional words were associated with increased activation of the amygdala. Finally, the direct condition, as compared to the indirect condition, led to enhanced activation to emotional vs. neutral words in the dorsomedial prefrontal cortex and the anterior cingulate cortex. These results suggest valence and arousal dependent brain activation patterns that are partially modulated by participants’ processing mode of the emotional stimuli.

HSQC–ADEQUATE correlation: a new paradigm for establishing a molecular skeleton

Various experimental methods have been developed to unequivocally identify vicinal neighbor carbon atoms. Variants of the HMBC experiment intended for this purpose have included 2J3J-HMBC and H2BC. The 1,1-ADEQUATE experiment, in contrast, was developed to accomplish the same goal but relies on the (1) J(CC) coupling between a proton-carbon resonant pair and the adjacent neighbor carbon. Hence, 1,1-ADEQUATE can identify non-protonated adjacent neighbor carbons, whereas the 2J3J-HMBC and H2BC experiments require both neighbor carbons to be protonated to operate. Since 1,1-ADEQUATE data are normally interpreted with close reference to an HSQC spectrum of the molecule in question, we were interested in exploring the unsymmetrical indirect covariance processing of multiplicity-edited GHSQC and 1,1-ADEQUATE spectra to afford an HSQC-ADEQUATE correlation spectrum that facilitates the extraction of carbon-carbon connectivity information. The HSQC-ADEQUATE spectrum of strychnine is shown and the means by which the carbon skeleton can be conveniently traced is discussed.

A Covariance NMR Toolbox for MATLAB and OCTAVE

The Covariance NMR Toolbox is a new software suite that provides a streamlined implementation of covariance-based analysis of multi-dimensional NMR data. The Covariance NMR Toolbox uses the MATLAB or, alternatively, the freely available GNU OCTAVE computer language, providing a user-friendly environment in which to apply and explore covariance techniques. Covariance methods implemented in the toolbox described here include direct and indirect covariance processing, 4D covariance, generalized indirect covariance (GIC), and Z-matrix transform. In order to provide compatibility with a wide variety of spectrometer and spectral analysis platforms, the Covariance NMR Toolbox uses the NMRPipe format for both input and output files. Additionally, datasets small enough to fit in memory are stored as arrays that can be displayed and further manipulated in a versatile manner within MATLAB or OCTAVE.

Auditory Warning Signals Affect Mechanisms of Response Selection

Irrelevant tone (accessory) stimuli facilitate performance in simple and choice reaction time tasks. In the present study, we combined accessory stimulation with a selective attention paradigm in order to investigate its influence on mechanisms of response selection. In the framework of a spatial stimulus-response compatibility task (Simon task), we tested whether accessory stimuli selectively affect bottom up triggered response activation processes (e.g., direct route processing), processing of task-relevant stimulus features (indirect route processing), or both/none. Results suggest a two-component effect of accessory stimuli within this selective attention task. First, accessory stimuli increased the Simon effect due to beneficial direct route processing. Second, accessory stimuli generally decreased reaction times indicating facilitation of indirect route processing.

Direct versus indirect processing changes the influence of color in natural scene categorization

We examined whether participants would use a negative priming (NP) paradigm to categorize color and grayscale images of natural scenes that were presented peripherally and were ignored. We focused on (1) attentional resources allocated to natural scenes and (2) direct versus indirect processing of them. We set up low and high attention-load conditions, based on the set size of the searched stimuli in the prime display (one and five). Participants were required to detect and categorize the target objects in natural scenes in a central visual search task, ignoring peripheral natural images in both the prime and probe displays. The results showed that, irrespective of attention load, NP was observed for color scenes but not for grayscale scenes. We did not observe any effect of color information in central visual search, where participants responded directly to natural scenes. These results indicate that, in a situation in which participants indirectly process natural scenes, color information is critical to object categorization, but when the scenes are processed directly, color information does not contribute to categorization.

Isoflavones, Flavan-3-ols, Phenolic Acids, Total Phenolic Profiles, and Antioxidant Capacities of Soy Milk As Affected by Ultrahigh-Temperature and Traditional Processing Methods

The objectives of this work were to assess antioxidant activities and phenolic compounds of soy milk as affected by traditional and ultrahigh-temperature (UHT) processing. Three soybean varieties were processed into raw soy milk and then cooked soy milk by indirect and direct UHT methods (both at 143 degrees C for 60 s) and traditional cooking (stove cooking and steam injection) methods (both at 100 degrees C for 20 min). Total phenolic content (TPC), total flavonoid content (TFC), phenolic acids, isoflavones, flavan-3-ols, and anthocyanins were quantified. DPPH free radical scavenging activity, ferric reducing antioxidant power (FRAP), and oxygen radical absorbance capacity (ORAC) were analyzed. As compared to the raw soy milk, all thermal processing significantly (p < 0.05) reduced TPC values and significantly (p < 0.05) increased TFC values for all soybean varieties. All processing methods significantly (p < 0.05) increased DPPH and FRAP values in the soy milk processed from yellow soybean varieties Proto and IA 2032. UHT processing increased their ORAC values, but traditional and steam processing reduced their ORAC values. However, in the case of the soy milk from black soybean, all processing reduced ORAC values as compared to the raw soy milk. None of processing affected total phenolic acids, chlorogenic, and trans-cinnamic acid, as well as (+)-catechin. However, all processing significantly (p < 0.05) affected contents of total isoflavones and individual isoflavones. Thermal processing caused significant (p < 0.05) increases in 7-O-beta-glucosides and acetylglucosides, but caused significant (p < 0.05) decreases in malonylglucosides and aglycones. Indirect UHT processing transformed more isoflavones from malonylglucosides into 7-O-beta-glucosides than the direct UHT did.

Fatigue behaviour of dental composite materials

Objective The intent of the project was to evaluate the fatigue behavior of particle and fiber filled dental composites that are fabricated either directly or indirectly using a notched specimen with respect to the number of cycles until failure. Methods The materials were five dental composites, three normally cured in the oral cavity (Restolux, Renew and Filtek Supreme), direct processing, and two laboratory produced (BelleGlass, and Tescera), indirect processing. The specimens were 3 mm × 3 mm × 25 mm bars with a 0.75 or 1.0 mm notch in the mid-span of the bars, polished with 320 grit SiC paper and aged for 6 months in air, distilled water, artificial saliva, and a 50/50 mixture of ethanol and distilled water. Testing was performed with a stress mean range of 5–49 MPa, the maximum number of cycles was 100,000, and the number of cycles to failure was recorded. Results For the specimens that failed, BelleGlass, Restolux, and Tescera were able to withstand a higher cyclic loaded stress than Renew and Filtek. The 50/50 by volume mixture of water and ethanol resulted in the lowest resistance to fatigue for all materials. Conclusions Of the dental composite materials investigated, the indirect processed and those with large particle fillers (higher weight percent filler) had better cyclic fatigue resistance than micro- and nano-particle fillers (lower weight percent filler).

Unsymmetrical indirect covariance processing of hyphenated and long‐range heteronuclear 2D NMR spectra ‐ Enhanced visualization of 2JCH and 4JCH correlation responses

Abstractmagnified imageRecent reports have demonstrated the unsymmetrical indirect covariance combination of discretely acquired 2D NMR experiments into spectra that provide an alternative means of accessing the information content of these spectra. The method can be thought of as being analogous to the Fourier transform conversion of time domain data into the more readily interpreted frequency domain. Hyphenated 2D‐NMR spectra such as GHSQC‐TOCSY, when available, provide an investigator with the means of sorting proton‐proton homonuclear connectivity networks as a function of the 13C chemical shift of the carbon directly bound to the proton from which propagation begins. Long‐range heteronuclear chemical shift correlation experiments establish proton‐carbon correlations via heteronuclear coupling pathways, most commonly across three bonds (3JCH), but in more general terms across two (2JCH) to four bonds (4JCH). In many instances 3JCH correlations dominate GHMBC spectra. We demonstrate in this report the improved visualization of 2JCH and 4JCH correlations through the unsymmetrical indirect covariance processing of GHSQC‐TOCSY and GHMBC 2D spectra.

Development of Aberration-Corrected Electron Microscopy

The successful correction of spherical aberration is an exciting and revolutionary development for the whole field of electron microscopy. Image interpretability can be extended out to sub-Angstrom levels, thereby creating many novel opportunities for materials characterization. Correction of lens aberrations involves either direct (online) hardware attachments in fixed-beam or scanning TEM or indirect (off-line) software processing using either off-axis electron holography or focal-series reconstruction. This review traces some of the important steps along the path to realizing aberration correction, including early attempts with hardware correctors, the development of online microscope control, and methods for accurate measurement of aberrations. Recent developments and some initial applications of aberration-corrected electron microscopy using these different approaches are surveyed. Finally, future prospects and problems are briefly discussed.

Designing Structure of Operations of Technological Ppocess of Machining Shafts in CIM Considering the Technological Inheritance

The article presents the mechanism of residual stress force appearance at individual stages of the manufacturing process, which is one of main causes of processing inaccuracy. A mathematical description of the phenomenon of operation inheritance and gradual accumulation of errors is introduced. The influence of the technological inheritance on the final processing accuracy is discussed on the example of precise parts manufacturing. A new order of processing is suggested, excluding a number of indirect thermal processing operations. Proposal of comprehensive solution for low stiffness shaping accuracy control unit is presented in the article. Solving the problem is not easy due to the fact that during every part process, the part successively inherits and accumulates errors from previous operations, which is hard do estimate. Two shafts processing technologies - base and recommended - are described. The base variant contains 15 basic operations. The recommended variant is expected to decrease the cycle count as a result of applying new technical solutions. Applying analytical relations leads to increase of processing accuracy while making the process less labour-intensive and producing parts with better outer layer quality.

Using indirect covariance spectra to identify artifact responses in unsymmetrical indirect covariance calculated spectra

Several groups of authors have reported studies in the areas of indirect and unsymmetrical indirect covariance NMR processing methods. Efforts have recently focused on the use of unsymmetrical indirect covariance processing methods to combine various discrete two-dimensional NMR spectra to afford the equivalent of the much less sensitive hyphenated 2D NMR experiments, for example indirect covariance (icv)-heteronuclear single quantum coherence (HSQC)-COSY and icv-HSQC-nuclear Overhauser effect spectroscopy (NOESY). Alternatively, unsymmetrical indirect covariance processing methods can be used to combine multiple heteronuclear 2D spectra to afford icv-13C-15N HSQC-HMBC correlation spectra. We now report the use of responses contained in indirect covariance processed HSQC spectra as a means for the identification of artifacts in both indirect covariance and unsymmetrical indirect covariance processed 2D NMR spectra.

13C−15N Correlation via Unsymmetrical Indirect Covariance NMR: Application to Vinblastine

Unsymmetrical indirect covariance processing methods allow the derivation of hyphenated 2D NMR data from the component 2D spectra, potentially circumventing the acquisition of the much lower sensitivity hyphenated 2D NMR experimental data. Calculation of HSQC-COSY and HSQC-NOESY spectra from GHSQC, COSY, and NOESY spectra, respectively, has been reported. The use of unsymmetrical indirect covariance processing has also been applied to the combination of (1)H- (13)C GHSQC and (1)H- (15)N long-range correlation data (GHMBC, IMPEACH, or CIGAR-HMBC). The application of unsymmetrical indirect covariance processing to spectra of vinblastine is now reported, specifically the algorithmic extraction of (13)C- (15)N correlations via the unsymmetrical indirect covariance processing of the combination of (1)H- (13)C GHSQC and long-range (1)H- (15)N GHMBC to produce the equivalent of a (13)C- (15)N HSQC-HMBC correlation spectrum. The elimination of artifact responses with aromatic solvent-induced shifts (ASIS) is shown in addition to a method of forecasting potential artifact responses through the indirect covariance processing of the GHSQC spectrum used in the unsymmetrical indirect covariance processing.

The Effects of Mass Flow Rate in an Indirect Ultra-High Temperature Processing System

The Effects of Mass Flow Rate in an Indirect Ultra-High Temperature Processing System

Residual water suppression by indirect covariance NMR

Residual water solvent signals in 2D NMR experiments adversely affect appearance and subsequent analysis of spectra. A method for water suppression that is based on indirect covariance processing is described. It produces a symmetric spectrum with a water signal that is substantially decreased or completely absent. The method, which can be combined with other water suppression schemes, is demonstrated for 2D TOCSY, NOESY, and ROESY spectra of the protein, ubiquitin in aqueous solution.

Application of unsymmetrical indirect covariance NMR methods to the computation of the 13C↔15N HSQC‐IMPEACH and 13C↔15N HMBC‐IMPEACH correlation spectra

Utilization of long-range (1)H--(15)N heteronuclear chemical shift correlation has continually grown in importance since the first applications were reported in 1995. More recently, indirect covariance NMR methods have been introduced followed by the development of unsymmetrical indirect covariance processing methods. The latter technique has been shown to allow the calculation of hyphenated 2D NMR data matrices from more readily acquired nonhyphenated 2D NMR spectra. We recently reported the use of unsymmetrical indirect covariance processing to combine (1)H--(13)C GHSQC and (1)H--(15)N GHMBC long-range spectra to yield a (13)C--(15)N HSQC-HMBC chemical shift correlation spectrum that could not be acquired in a reasonable period of time without resorting to (15)N-labeled molecules. We now report the unsymmetrical indirect covariance processing of (1)H--(13)C GHMBC and (1)H--(15)N IMPEACH spectra to afford a (13)C--(15)N HMBC-IMPEACH spectrum that has the potential to span as many as six to eight bonds. Correlations for carbon resonances long-range coupled to a protonated carbon in the (1)H--(13)C HMBC spectrum are transferred via the long-range (1)H--(15)N coupling pathway in the (1)H--(15)N IMPEACH spectrum to afford a much broader range of correlation possibilities in the (13)C--(15)N HMBC-IMPEACH correlation spectrum. The indole alkaloid vincamine is used as a model compound to illustrate the application of the method.

Using Unsymmetrical Indirect Covariance Processing to Calculate GHSQC-COSY Spectra

GHSQC-TOCSY experiments allow sorting of proton-proton connectivity information as a function of (13)C chemical shift. GHSQC-TOCSY is a relatively insensitive 2D NMR experiment. Given two coherence transfer experiments, A --> B and A --> C, it is possible to indirectly determine B <--> C. Unsymmetrical indirect covariance processing of a (1)H- (13)C GHSQC and a GCOSY spectrum afforded a GHSQC-COSY spectrum, with an information content analogous to a GHSQC-TOCSY experiment. However, GHSQC-TOCSY is of significantly lower sensitivity and the data require considerably more time to acquire than either of the component experiments. Investigators needing access to GHSQC-TOCSY type data can, in principle, access it from more readily acquired 2D NMR data. Strychnine ( 1) was used as a model compound to illustrate this capability.

Utilizing unsymmetrical indirect covariance processing to define 15N13C connectivity networks

There has been considerable interest over the past decade in the utilization of direct and long-range 1H- 15N heteronuclear shift correlation methods at natural abundance to facilitate the elucidation of small molecule structures. Recently, there has also been a high level of interest in the exploration of indirect covariance NMR methods. Our initial explorations in this area led to the development of unsymmetrical indirect covariance methods, which allow the calculation of hyphenated 2D NMR spectra such as 2D GHSQC-COSY and GHSQC-NOESY from the discrete component 2D NMR experiments. We now wish to report the utilization of unsymmetrical indirect covariance NMR methods for the combination of 1H- 13C GHSQC and 1H- 15N long-range (GHMBC, IMPEACH-MBC, CIGAR-HMBC, etc.) heteronuclear chemical shift correlation spectra to determine 15N- 13C correlation pathways.

Image enhancement – An emergent pattern formation approach via decentralised multi-agent systems

A multi-agent framework inspired by natural and physical systems is presented for data discovery and image enhancement. The input image is represented as a topographic landscape upon which a large population of independent simple, reactive, mobile agents resides. The local landscape configuration presents stimuli to each agent, influencing agent behaviour and resulting in changes in agent orientation and movement. Individual agents deposit a trail as they move and leave specific marks in response to stimuli above a certain threshold. The parallel interactions of the agent population and the image landscape result in emergent patterns of trails and marks being generated, corresponding to global (population level) perception of the original image. The emergent patterns exhibit image feature extraction and represent an indirect processing of the input image. External environmental pressures may be applied to the emergent patterns to further amplify the feature extraction. The framework represents a decentralised approach to image enhancement which is extensible. Different types of agent may be developed to perform different image processing functions, or other problems whose definition and solution may be represented as spatial patterns. Results including binary image processing, greyscale enhancement, colour image processing and related spatial processing problems are presented.