True chemical shift correlation maps:a TOCSY experiment with pure shifts in both dimensions

Signal resolution in H NMR is limited primarily by multiplet structure. Recent advances in pure shift NMR, in which the effects of homonuclear couplings are suppressed, have allowed this limitation to be circumvented in 1D NMR, gaining almost an order of magnitude in spectral resolution. Here for the first time an experiment is demonstrated that suppresses multiplet structure in both domains of a homonuclear two-dimensional spectrum. The principle is demonstrated for the TOCSY experiment, generating a chemical shift correlation map in which a single peak is seen for each coupled relationship, but the principle is general and readily extensible to other homonuclear correlation experiments. Such spectra greatly simplify manual spectral analysis and should be well-suited to automated methods for structure elucidation. © 2010 American Chemical Society.

Serial correlation in the returns of UK capitalization based portfolios

This article examines whether UK portfolio returns are time varying so that expected returns follow an AR(1) process as proposed by Conrad and Kaul for the USA. It explores this hypothesis for four portfolios that have been formed on the basis of market capitalization. The portfolio returns are modelled using a kalman filter signal extraction model in which the unobservable expected return is the state variable and is allowed to evolve as a stationary first order autoregressive process. It finds that this model is a good representation of returns and can account for most of the autocorrelation present in observed portfolio returns. This study concludes that UK portfolio returns are time varying and the nature of the time variation appears to introduce a substantial amount of autocorrelation to portfolio returns. Like Conrad and Kaul if finds a link between the extent to which portfolio returns are time varying and the size of firms within a portfolio but not the monotonic one found for the USA. © 2004 Taylor and Francis Ltd.

Measuring the spatial extent of texture pooling using reverse correlation

The local image representation produced by early stages of visual analysis is uninformative regarding spatially extensive textures and surfaces. We know little about the cortical algorithm used to combine local information over space, and still less about the area over which it can operate. But such operations are vital to support perception of real-world objects and scenes. Here, we deploy a novel reverse-correlation technique to measure the extent of spatial pooling for target regions of different areas placed either in the central visual field, or more peripherally. Stimuli were large arrays of micropatterns, with their contrasts perturbed individually on an interval-by-interval basis. By comparing trial-by-trial observer responses with the predictions of computational models, we show that substantial regions (up to 13 carrier cycles) of a stimulus can be monitored in parallel by summing contrast over area. This summing strategy is very different from the more widely assumed signal selection strategy (a MAX operation), and suggests that neural mechanisms representing extensive visual textures can be recruited by attention. We also demonstrate that template resolution is much less precise in the parafovea than in the fovea, consistent with recent accounts of crowding. © 2014 The Authors.

Long-range and high-resolution correlation optical time-domain reflectometry utilizing an all optical chaotic source

A high resolution optical time domain reflectometry (OTDR) based on an all-fiber chaotic source is demonstrated. We analyze the key factors limiting the operational range of such an OTDR, e.g., integral Rayleigh backscattering and the fiber loss, which degrade the optical signal to noise ratio at the receiver side, and then the guideline for counter-act such signal fading is discussed. The experimentally demonstrated correlation OTDR presents ability of 100km sensing range and 8.2cm spatial resolution (1.2 million resolved points), as a verification of the theoretical analysis. To the best of our knowledge, this is the first time that correlation OTDR measurement is performed over such a long distance with such high precision.

Long-range and high-precision correlation optical time-domain reflectometry utilizing an all-fiber chaotic source

We propose a long range, high precision optical time domain reflectometry (OTDR) based on an all-fiber supercontinuum source. The source simply consists of a CW pump laser with moderate power and a section of fiber, which has a zero dispersion wavelength near the laser's central wavelength. Spectrum and time domain properties of the source are investigated, showing that the source has great capability in nonlinear optics, such as correlation OTDR due to its ultra-wide-band chaotic behavior, and mm-scale spatial resolution is demonstrated. Then we analyze the key factors limiting the operational range of such an OTDR, e. g., integral Rayleigh backscattering and the fiber loss, which degrades the optical signal to noise ratio at the receiver side, and then the guideline for counter-act such signal fading is discussed. Finally, we experimentally demonstrate a correlation OTDR with 100km sensing range and 8.2cm spatial resolution (1.2 million resolved points), as a verification of theoretical analysis.

Correlation of detector dog alerts to cocaine decomposition products found in illicit forensic specimens

The volatile chemicals which comprise the odor of the illicit drug cocaine have been analyzed by adsorption onto activated charcoal followed by solvent elution and GC/MS analysis. A series of field tests have been performed to determine the dominant odor compound to which dogs alert. All of our data to date indicate that the dominant odor is due to the presence of methyl benzoate which is associated with the cocaine, rather than the cocaine itself. When methyl benzoate and cocaine are spiked onto U.S. currency, the threshold level of methyl benzoate required for a canine to signal an alert is typically 1-10 $\mu$g. Humans have been shown to have a sensitivity similar to dogs for methyl benzoate but with poorer selectivity/reliability. The dominant decomposition pathway for cocaine has been evaluated at elevated temperatures (up to 280$\sp\circ$C). Benzoic acid, but no detectable methyl benzoate, is formed. Solvent extraction and SFE were used to study the recovery of cocaine from U.S. currency. The amount of cocaine which could be recovered was found to decrease with time. ^

Signal processing of physiological signals for automated assessment of stress in computer users

The need to provide computers with the ability to distinguish the affective state of their users is a major requirement for the practical implementation of affective computing concepts. This dissertation proposes the application of signal processing methods on physiological signals to extract from them features that can be processed by learning pattern recognition systems to provide cues about a person's affective state. In particular, combining physiological information sensed from a user's left hand in a non-invasive way with the pupil diameter information from an eye-tracking system may provide a computer with an awareness of its user's affective responses in the course of human-computer interactions. In this study an integrated hardware-software setup was developed to achieve automatic assessment of the affective status of a computer user. A computer-based "Paced Stroop Test" was designed as a stimulus to elicit emotional stress in the subject during the experiment. Four signals: the Galvanic Skin Response (GSR), the Blood Volume Pulse (BVP), the Skin Temperature (ST) and the Pupil Diameter (PD), were monitored and analyzed to differentiate affective states in the user. Several signal processing techniques were applied on the collected signals to extract their most relevant features. These features were analyzed with learning classification systems, to accomplish the affective state identification. Three learning algorithms: Naïve Bayes, Decision Tree and Support Vector Machine were applied to this identification process and their levels of classification accuracy were compared. The results achieved indicate that the physiological signals monitored do, in fact, have a strong correlation with the changes in the emotional states of the experimental subjects. These results also revealed that the inclusion of pupil diameter information significantly improved the performance of the emotion recognition system. ^

Microfluidics-based single-cell functional proteomics microchip for portraying protein signal transduction networks within the framework of physicochemical principles, with applications in fundamental and translational cancer research

Single-cell functional proteomics assays can connect genomic information to biological function through quantitative and multiplex protein measurements. Tools for single-cell proteomics have developed rapidly over the past 5 years and are providing unique opportunities. This thesis describes an emerging microfluidics-based toolkit for single cell functional proteomics, focusing on the development of the single cell barcode chips (SCBCs) with applications in fundamental and translational cancer research.

The microchip designed to simultaneously quantify a panel of secreted, cytoplasmic and membrane proteins from single cells will be discussed at the beginning, which is the prototype for subsequent proteomic microchips with more sophisticated design in preclinical cancer research or clinical applications. The SCBCs are a highly versatile and information rich tool for single-cell functional proteomics. They are based upon isolating individual cells, or defined number of cells, within microchambers, each of which is equipped with a large antibody microarray (the barcode), with between a few hundred to ten thousand microchambers included within a single microchip. Functional proteomics assays at single-cell resolution yield unique pieces of information that significantly shape the way of thinking on cancer research. An in-depth discussion about analysis and interpretation of the unique information such as functional protein fluctuations and protein-protein correlative interactions will follow.

The SCBC is a powerful tool to resolve the functional heterogeneity of cancer cells. It has the capacity to extract a comprehensive picture of the signal transduction network from single tumor cells and thus provides insight into the effect of targeted therapies on protein signaling networks. We will demonstrate this point through applying the SCBCs to investigate three isogenic cell lines of glioblastoma multiforme (GBM).

The cancer cell population is highly heterogeneous with high-amplitude fluctuation at the single cell level, which in turn grants the robustness of the entire population. The concept that a stable population existing in the presence of random fluctuations is reminiscent of many physical systems that are successfully understood using statistical physics. Thus, tools derived from that field can probably be applied to using fluctuations to determine the nature of signaling networks. In the second part of the thesis, we will focus on such a case to use thermodynamics-motivated principles to understand cancer cell hypoxia, where single cell proteomics assays coupled with a quantitative version of Le Chatelier's principle derived from statistical mechanics yield detailed and surprising predictions, which were found to be correct in both cell line and primary tumor model.

The third part of the thesis demonstrates the application of this technology in the preclinical cancer research to study the GBM cancer cell resistance to molecular targeted therapy. Physical approaches to anticipate therapy resistance and to identify effective therapy combinations will be discussed in detail. Our approach is based upon elucidating the signaling coordination within the phosphoprotein signaling pathways that are hyperactivated in human GBMs, and interrogating how that coordination responds to the perturbation of targeted inhibitor. Strongly coupled protein-protein interactions constitute most signaling cascades. A physical analogy of such a system is the strongly coupled atom-atom interactions in a crystal lattice. Similar to decomposing the atomic interactions into a series of independent normal vibrational modes, a simplified picture of signaling network coordination can also be achieved by diagonalizing protein-protein correlation or covariance matrices to decompose the pairwise correlative interactions into a set of distinct linear combinations of signaling proteins (i.e. independent signaling modes). By doing so, two independent signaling modes – one associated with mTOR signaling and a second associated with ERK/Src signaling have been resolved, which in turn allow us to anticipate resistance, and to design combination therapies that are effective, as well as identify those therapies and therapy combinations that will be ineffective. We validated our predictions in mouse tumor models and all predictions were borne out.

In the last part, some preliminary results about the clinical translation of single-cell proteomics chips will be presented. The successful demonstration of our work on human-derived xenografts provides the rationale to extend our current work into the clinic. It will enable us to interrogate GBM tumor samples in a way that could potentially yield a straightforward, rapid interpretation so that we can give therapeutic guidance to the attending physicians within a clinical relevant time scale. The technical challenges of the clinical translation will be presented and our solutions to address the challenges will be discussed as well. A clinical case study will then follow, where some preliminary data collected from a pediatric GBM patient bearing an EGFR amplified tumor will be presented to demonstrate the general protocol and the workflow of the proposed clinical studies.

High Diagnostic Accuracy And Reproducibility Of Fine-needle Aspiration Cytology For Diagnosing Salivary Gland Tumors: Cytohistologic Correlation In 182 Cases.

The purpose of this study was to assess the efficacy and reproducibility of the cytologic diagnosis of salivary gland tumors (SGTs) using fine-needle aspiration cytology (FNAC). The study aimed to determine diagnostic accuracy, sensitivity, and specificity and to evaluate the extent of interobserver agreement. We retrospectively evaluated SGTs from the files of the Division of Pathology at the Clinics Hospital of São Paulo and Piracicaba Dental School between 2000 and 2006. We performed cytohistologic correlation in 182 SGTs. The sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy were 94%, 100%, 100%, 100%, and 99%, respectively. The interobserver cytologic reproducibility showed significant statistical concordance (P < .0001). FNAC is an effective tool for performing a reliable preoperative diagnosis in SGTs and shows high diagnostic accuracy and consistent interobserver reproducibility. Further FNAC studies analyzing large samples of malignant SGTs and reactive salivary lesions are needed to confirm their accuracy.

Core-valence Correlation Effects On Ir Calculations: The Bf3 And Bcl3 Cases.

The first theoretical results of core-valence correlation effects are presented for the infrared wavenumbers and intensities of the BF3 and BCl3 molecules, using (double- and triple-zeta) Dunning core-valence basis sets at the CCSD(T) level. The results are compared with those calculated in the frozen core approximation with standard Dunning basis sets at the same correlation level and with the experimental values. The general conclusion is that the effect of core-valence correlation is, for infrared wavenumbers and intensities, smaller than the effect of adding augmented diffuse functions to the basis set, e.g., cc-pVTZ to aug-cc-pVTZ. Moreover, the trends observed in the data are mainly related to the augmented functions rather than the core-valence functions added to the basis set. The results obtained here confirm previous studies pointing out the large descrepancy between the theoretical and experimental intensities of the stretching mode for BCl3.

Measuring The Hydrodynamic Radius Of Quantum Dots By Fluorescence Correlation Spectroscopy.

Fluorescence Correlation Spectroscopy (FCS) is an optical technique that allows the measurement of the diffusion coefficient of molecules in a diluted sample. From the diffusion coefficient it is possible to calculate the hydrodynamic radius of the molecules. For colloidal quantum dots (QDs) the hydrodynamic radius is valuable information to study interactions with other molecules or other QDs. In this chapter we describe the main aspects of the technique and how to use it to calculate the hydrodynamic radius of quantum dots (QDs).

Correlation Between Cephalometric Data And Severity Of Sleep Apnea.

Obstructive sleep apnea syndrome has a high prevalence among adults. Cephalometric variables can be a valuable method for evaluating patients with this syndrome. To correlate cephalometric data with the apnea-hypopnea sleep index. We performed a retrospective and cross-sectional study that analyzed the cephalometric data of patients followed in the Sleep Disorders Outpatient Clinic of the Discipline of Otorhinolaryngology of a university hospital, from June 2007 to May 2012. Ninety-six patients were included, 45 men, and 51 women, with a mean age of 50.3 years. A total of 11 patients had snoring, 20 had mild apnea, 26 had moderate apnea, and 39 had severe apnea. The distance from the hyoid bone to the mandibular plane was the only variable that showed a statistically significant correlation with the apnea-hypopnea index. Cephalometric variables are useful tools for the understanding of obstructive sleep apnea syndrome. The distance from the hyoid bone to the mandibular plane showed a statistically significant correlation with the apnea-hypopnea index.

Histologic Correlation Of Expression Of Ki-67 In Squamous Cell Carcinoma Of The Glottis According To The Degree Of Cell Differentiation.

Squamous cell carcinoma is the most common neoplasm of the larynx and glottis, and its prognosis depends on the size of the lesion, level of local invasion, cervical lymphatic spread, and presence of distant metastases. Ki-67 (MKI67) is a protein present in the core, whose function is related to cell proliferation. To evaluate the expression of marker Ki-67 in squamous cell carcinoma of the larynx and glottis and its correlation to pathological findings. Experimental study with immunohistochemistry analysis of Ki-67, calculating the percentage of the cell proliferation index in glottic squamous cell carcinomas. Sixteen cases were analyzed, with six well-differentiated and 10 poorly/moderately differentiated tumors. There was a correlation between cell proliferation index and degree of cell differentiation, with higher proliferation in poorly/moderately differentiated tumors. The cell proliferation index, as measured by Ki-67, may be useful in the characterization of histological degree in glottic squamous cell tumors.

Correlation Between Testosterone And Psa Kinetics In Metastatic Prostate Cancer Patients Treated With Diverse Chemical Castrations.

To assess total testosterone and prostatic-specific antigen (PSA) kinetics among diverse chemical castrations, advanced-stage prostate cancer patients were randomized into three groups of 20: Group 1, Leuprolide 3.75 mg; Group 2, Leuprolide 7.5 mg; and Group 3, Goserelin 3.6 mg. All groups were treated with monthly application of the respective drugs. The patients' levels of serum total testosterone and PSA were evaluated at two time periods: before the treatment and 3 months after the treatment. Spearman's rank correlation coefficient was utilized to verify the hypothesis of linear correlation between total testosterone and PSA levels. At the beginning the patients' age, stage, grade, PSA, and total testosterone were similar within the three groups, with median age 72, 70, and 70 years in Groups 1, 2, and 3, respectively. Three months after the treatment, patients who received Leuprolide 7.5 mg presented significantly lower median total testosterone levels compared with Goserelin 3.6 mg and Leuprolide 3.75 mg (9.5 ng/dL vs. 20.0 ng/dL vs. 30.0 ng/dL, respectively; p = .0072), while those who received Goserelin 3.6 mg presented significantly lower PSA levels compared with Leuprolide 7.5 mg and Leuprolide 3.75 mg (0.67 vs. 1.86 vs. 2.57, respectively; p = .0067). There was no linear correlation between total testosterone and PSA levels. Overall, regarding castration levels of total testosterone, 28.77% of patients did not obtain levels ≤50 ng/dL and 47.80% did not obtain levels ≤20 ng/dL. There was no correlation between total testosterone and PSA kinetics and no equivalence among different pharmacological castrations.

Human Herpesvirus-6 And Cytomegalovirus Dna In Liver Donor Biopsies And Their Correlation With Hla Matches And Acute Cellular Rejection.

Herpesvirus reactivation is common after liver transplantation. Analyze the presence of cytomegalovirus (HCMV) and human herpesvirus-6 (HHV-6) DNA in liver donor biopsies, seeking to better understand issues involving human donor leukocyte antigens (HLA)-A, B and DR, as well as correlations with acute cellular rejection. Fifty-nine liver transplantation patients were investigated for the presence of HCMV and HHV-6 DNA in liver donor biopsies, using the Nested-PCR technique. The clinical donor information and HLA matches were obtained from the São Paulo State Transplant System. The recipients' records regarding acute cellular rejection were studied. Seven (11.8%) biopsies were positive for HCMV DNA and 29 (49%) were positive for HHV-6 DNA. In 14 donors with HLA-DR 15 nine had HHV-6 DNA positive liver biopsy with a tendency for significant association (p=0.09), 22 recipients developed acute cellular rejection and 9/22 were positive for HLA-DR 15 (p=0.03; χ(2)=4.51), which was statistically significant in univariate analysis and showed a tendency after multivariate analysis (p=0.08). HHV-6 DNA was prevalent in liver donors studied as well as HLA-DR 15. These findings suggest that patients with HLA-DR 15 in liver donor biopsies develop more rejection after liver transplantation.