gebhart/patrepeval huggingface dataset:
Classified biomarker panel with tau microtubule binding regions identifies pathophysiological changes in Alzheimer’s disease continuum (2021)

Abstract Background Accumulations of tau aggregates and amyloid plaques in brain are hallmarks of Alzheimer’s disease (AD). Recent studies in characterizing tau species, especially phosphorylated tau‐181 (p‐tau181) and p‐tau217 in AD brain and biofluids suggested that these species start increasing at preclinical stage, correlate with amyloid plaques, and improve the diagnosis. However, it is still unclear if these changes in p‐tau reflect tau pathology in AD. Recently, we identified truncated tau species containing microtubule binding regions, e.g., residues 243‐254 (MTBR‐tau243) and 299‐317 (MTBR‐tau299), associate with tau pathology in AD brain. In this study, we show how these MTBR‐tau change and correlate with p‐tau species in AD cerebrospinal fluid (CSF). We discuss the potential use of these composite biomarker panel to understand whole AD continuum. Method We established methods to quantify more than dozen of CSF tau species including MTBR‐tau and p‐tau, using immunoprecipitation or chemical extraction followed by mass spectrometry analysis. These methods were applied to CSF analyses of several sporadic AD cohorts. Subsets of the participants were assessed for brain tau aggregation measured by positron emission tomography (PET) to investigate the correlations with various CSF tau biomarkers. Result CSF MTBR‐tau were specifically increased in amyloid positive group. Especially, MTBR‐tau299 showed the most significant increase even in preclinical stage and discriminated amyloid status (AUC=0.923), whereas the correlation with tau‐PET measure was moderate (Spearman r=0.458) and the increase was saturated at high tau‐PET measure. MTBR‐tau243 showed the best correlation with tau‐PET measure (Spearman r=0.759) in all tau species quantified in this study and no saturation was observed. MTBR‐tau299 was the most highly correlated with p‐tau217 (Spearman r=0.849), suggesting MTBR‐tau299 is highly corresponding to amyloid pathology. Notably, the phosphorylation occupancy at p‐tau217 was also saturated at high tau‐PET measure as seen in MTBR‐tau299. Conclusion MTBR‐tau complement p‐tau to classify biomarker panel to stage AD, reflecting tau as well as amyloid pathology in whole AD continuum. Of note, it remains to be addressed if p‐tau217 increases in response to amyloid plaques rather than tau tangles.
Integration of programmable microfluidics and on-chip fluorescence detection for biosensing applications (2014)

We describe the integration of an actively controlled programmable microfluidic sample processor with on-chip optical fluorescence detection to create a single, hybrid sensor system. An array of lifting gate microvalves (automaton) is fabricated with soft lithography, which is reconfigurably joined to a liquid-core, anti-resonant reflecting optical waveguide (ARROW) silicon chip fabricated with conventional microfabrication. In the automaton, various sample handling steps such as mixing, transporting, splitting, isolating, and storing are achieved rapidly and precisely to detect viral nucleic acid targets, while the optofluidic chip provides single particle detection sensitivity using integrated optics. Specifically, an assay for detection of viral nucleic acid targets is implemented. Labeled target nucleic acids are first captured and isolated on magnetic microbeads in the automaton, followed by optical detection of single beads on the ARROW chip. The combination of automated microfluidic sample preparation and highly sensitive optical detection opens possibilities for portable instruments for point-of-use analysis of minute, low concentration biological samples.
Laser-induced transepidermal elimination of dermal content by fractional photothermolysis (2006)

The wound healing process in skin is studied in human subjects treated with fractional photothermolysis. In-vivo histological evaluation of vacuoles formed over microthermal zones (MTZs) and their content is undertaken. A 30-W, 1550-nm single-mode fiber laser system delivers an array of 60 microm or 140 microm 1e2 incidence microbeam spot size at variable pulse energy and density. Treatments span from 6 to 20 mJ with skin excisions performed 1-day post-treatment. Staining with hematoxylin and eosin demonstrates an intact stratum corneum with vacuolar formation within the epidermis. The re-epithelialization process with repopulation of melanocytes and keratinocytes at the basal layer is apparent by 1-day post-treatment. The dermal-epidermal (DE) junction is weakened and separated just above zones of dermal coagulation. Complete loss of dermal cell viability is noted within the confines of the MTZs 1-day post-treatment, as assessed by lactate dehydrogenase. All cells falling outside the irradiation field remain viable. Content within the epidermal vacuoles stain positively with Gomori trichrome, suggesting a dermal origin. However, the positive staining could be due to loss of specificity after thermal alteration. Nevertheless, this dermal extrusion hypothesis is supported by very specific positive staining with an antihuman elastin antibody. Fractional photothermolysis creates microthermal lesions that allow transport and extrusion of dermal content through a compromised DE junction. Some dermal material is incorporated into the microepidermal necrotic debris and shuttled up the epidermis to eventually be exfoliated through the stratum corneum. This is the first report of a nonablative laser-induced transport mechanism by which dermal content can be predictably extruded biologically through the epidermis. Thus, treatment with the 1550-nm fiber laser may provide the first therapeutic option for clinical indications, including pigmentary disorders such as medically recalcitrant melasma, solar elastosis, as well as depositional diseases such as mucinosis and amyloidosis.
Capillary pressure model predicts distance to gas/water, oil/water contact (1993)

Gas/water and oil/water contacts can be predicted by a method based on a new capillary pressure model that relates four quantities: porosity, water saturation, air permeability, and capillary pressure. This advanced capillary pressure method, Adcap, provides integration of laboratory-measured capillary pressure (P[sub c]) data with routine log and core analysis. In the absence of laboratory P[sub c] data, the model depends on correlations from data obtained worldwide. Water levels are predicted through regression analysis using porosity and water saturation from log and/or core analysis. An important statistical result of the regression analysis is that an error range can be assigned to the predicted water level.
Detection of ultrarare somatic mutation in the human<i>TP53</i>gene by bidirectional pyrophosphorolysis-activated polymerization allele-specific amplification (2006)

The detection of ultra-rare mutation in the presence of excess amounts of normal genomic DNA is highly advantageous in a number of circumstances, including: 1) identification of minimal residual disease for improved cancer chemotherapy; 2) measurement of mutation load to assess environmental mutagen exposure or endogenous DNA repair; and 3) prenatal diagnosis of paternally-derived mutations within fetal cells in the maternal circulation. Bidirectional pyrophosphorolysis activated polymerization allele-specific amplification (Bi-PAP-A) utilizes two opposing 3'-terminal blocked oligonucleotides (P(*)s) with 1 nucleotide overlap at their 3' termini. The selectivity of Bi-PAP-A derives from the serial coupling of pyrophosphorolysis and DNA polymerization. A total of 13 Bi-PAP-A assays were developed and validated for the human p53 gene (TP53). The sensitivity and specificity of each assay were determined with mutated and wild-type DNA templates, respectively. Bi-PAP-A has a sensitivity of one molecule for most assays and a selectivity (sensitivity:specificity) greater than 1:10(7)-1:10(9) for four of all six mutation types. Four assays with high selectivity were used to detect rare somatic mutations in blood white cells. The silent g.13147C>G (p.R156) mutation was present at an estimated frequency of 1.1 x 10(-7). The g.14523A>T (p.E285V), g.14487G>C (p.R273P), and g.14060G>C (p.G245R) mutations were undetectable with frequencies less than 2.0 x 10(-8). We conclude that Bi-PAP-A is a general and rapid method for detecting ultra-rare mutations.
A 60 GHz 25% tuning range frequency generator with implicit divider based on third harmonic extraction with 182 dBc/Hz FoM (2015)

A 60 GHz frequency generator with implicit ÷3 divider is proposed in this work to improve the system-level efficiency and phase noise. A third-harmonic boosting technique is utilized to simultaneously generate 20GHz and sufficiently strong 60 GHz signals in order to avoid any divider operating at 60 GHz. The prototype is fabricated in 40nm CMOS and exhibits a phase noise of -100 dBc/Hz at 1MHz offset from 60 GHz carrier and 25% tuning range. The phase noise and FoM <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">T</sub> (figure-of-merit with tuning range) are improved by 5 dB and 4.6 dB, respectively, compared to state-of-the-art.
Multi-Dimensional Feature Merger for Question Answering (2012)

In this paper, we introduce new features for question-answering systems. These features are inspired by the fact that justification of the correct answer (out of many candidate answers) may be present in multiple passages. Our features attempt to combine evidence from multiple passages retrieved for a candidate answer. We present results on two data-sets: Jeopardy! and Doctor’s Dilemma. In both data-sets, our features are ranked highest in correlation with gold class (in the training data) and significantly improve the performance of our existing QA system, Watson.
Polystyrene‐supported metallocene catalysts for olefin polymerizations (1995)

Abstract Several kinds of polystyrene‐supported metallocene catalysts were prepared and used in the polymerizations of propylene and ethylene with methylaluminoxane (MAO) as cocatalyst. It was found that these catalysts are stable even at 70°C. They display fairly high activities when the polymerizations are conducted at high temperatures.
Accumulation of Single-Stranded DNA and Destabilization of Telomeric Repeats in Yeast Mutant Strains Carrying a Deletion of <i>RAD27</i> (1999)

The Saccharomyces cerevisiae RAD27 gene encodes the yeast homologue of the mammalian FEN-1 nuclease, a protein that is thought to be involved in the processing of Okazaki fragments during DNA lagging-strand synthesis. One of the predicted DNA lesions occurring in rad27 strains is the presence of single-stranded DNA of the template strand for lagging-strand synthesis. We examined this prediction by analyzing the terminal DNA structures generated during telomere replication in rad27 strains. The lengths of the telomeric repeat tracts were found to be destabilized in rad27 strains, indicating that naturally occurring direct repeats are subject to tract expansions and contractions in such strains. Furthermore, abnormally high levels of single-stranded DNA of the templating strand for lagging-strand synthesis were observed in rad27 cells. Overexpression of Dna2p in wild-type cells also yielded single-stranded DNA regions on telomeric DNA and caused a cell growth arrest phenotype virtually identical to that seen for rad27 cells grown at the restrictive temperature. Furthermore, overexpression of the yeast exonuclease Exo1p alleviated the growth arrest induced by both conditions, overexpression of Dna2p and incubation of rad27 cells at 37 degrees C. However, the telomere heterogeneity and the appearance of single-stranded DNA are not prevented by the overexpression of Exo1p in these strains, suggesting that this nuclease is not simply redundant with Rad27p. Our data thus provide in vivo evidence for the types of DNA lesions predicted to occur when lagging-strand synthesis is deficient and suggest that Dna2p and Rad27p collaborate in the processing of Okazaki fragments.
Long-term monitoring of acute wound healing from beneath the primary wound dressings (2018)

Our group has developed a quasimonopolar bioimpedance measurement-based method and a measurement system to determine the status of wound healing. So far, we have shown that the bioimpedance method is a prospective tool for assessment of wound healing by monitoring the healing of both acute wounds and venous ulcers at discrete time points. The objective of this study was to demonstrate that the method is capable for monitoring wound healing also long-term while the wound is covered by the primary dressings. For this purpose we arranged a follow-up study of a single acute wound. The purpose-built multi-electrode dressing was applied on the wound and left under the primary dressings until the complete re-epithelization was achieved. The bioimpedance of the wound and surrounding skin area was measured regularly during a 120 hours study. Based on the results, we can confirm that the method applies for long-term monitoring of acute wound healing without necessity to remove the primary dressings.
Discrete Multi-Tone for 100 Gb/s Optical Access Networks (2014)

Discrete Multi-Tone (DMT) is an attractive technology for short reach optical transmission systems. We have reported several results on transmission experiments using DMT. In this paper we review this technology and these experimental results.
High-performance long wavelength superlattice infrared detectors (2010)

The nearly lattice-matched InAs/GaSb/AlSb (antimonide) material system offers tremendous flexibility in realizing high-performance infrared detectors. Antimonide-based superlattice (SL) detectors can be tailor-made to have cutoff wavelengths ranging from the short wave infrared (SWIR) to the very long wave infrared (VLWIR). SL detectors are predicted to have suppressed Auger recombination rates and low interband tunneling, resulting in the suppressed dark currents. Moreover, the nearly lattice-matched antimonide material system, consisting of InAs, GaSb, AlSb and their alloys, allows for the construction of superlattice heterostructures. In particular, unipolar barriers, which blocks one carrier type without impeding the flow of the other, have been implemented in the design of SL photodetectors to realize complex heterodiodes with improved performance. Here, we report our recent efforts in achieving state-of-the-art performance in antimonide superlattice based infrared photodetectors.
An Operator Formulation of the Multiscale Finite-Volume Method with Correction Function (2009)

The multiscale finite-volume (MSFV) method has been derived to efficiently solve large problems with spatially varying coefficients. The fine-scale problem is subdivided into local problems that can be solved separately and are coupled by a global problem. This algorithm, in consequence, shares some characteristics with two-level domain decomposition (DD) methods. However, the MSFV algorithm is different in that it incorporates a flux reconstruction step, which delivers a fine-scale mass conservative flux field without the need for iterating. This is achieved by the use of two overlapping coarse grids. The recently introduced correction function allows for a consistent handling of source terms, which makes the MSFV method a flexible algorithm that is applicable to a wide spectrum of problems. It is demonstrated that the MSFV operator, used to compute an approximate pressure solution, can be equivalently constructed by writing the Schur complement with a tangential approximation of a single-cell overlapping grid and incorporation of appropriate coarse-scale mass-balance equations.
The effect of manganese and sulfur on the development of orientation (110) [001]-oriented low-alloy iron (1981)

An investigation was made to determine the role of manganese and sulfur concentration on the development of (110) [001] orientation in low-alloy iron specimens by primary recrystallization and normal grain growth. Fifteen heats, containing nominally 0.8% Si and 0.6% Cr with varying Mn and S contents, were used for the study, with three-stage processing to 0.15 mm thick strip. The manganese content was varied between 0 and 0.15% with nominal sulfur contents of 0.001, 0.006, and 0.012%. Torque and magnetic properties, as well as X-ray pole figures, were used to evaluate the orientation after final annealing. The low-sulfur alloys (0.001% S) did not develop the best (110) [001] orientations. Those specimens containing the higher sulfur concentrations (0.012% were poorly oriented, except for one specimen which contained essentially zero Mn (&lt;0.01%). All the specimens with nominal 0.006% S content developed strong (110) [001] textures with B10 values of up to 1.93 T and 60 Hz core losses at 1.7T as low as 1.5 W/kg.
Vascular Deformation Mapping (VDM) of Thoracic Aortic Enlargement in Aneurysmal Disease and Dissection (2017)

Thoracic aortic aneurysm is a common and lethal disease that requires regular imaging surveillance to determine timing of surgical repair and prevent major complications such as rupture. Current cross-sectional imaging surveillance techniques, largely based on computed tomography angiography, are focused on measurement of maximal aortic diameter, although this approach is limited to fixed anatomic positions and is prone to significant measurement error. Here we present preliminary results showing the feasibility of a novel technique for assessing change in aortic dimensions, termed vascular deformation mapping (VDM). This technique allows quantification of 3-dimensional changes in the aortic wall geometry through nonrigid coregistration of computed tomography angiography images and spatial Jacobian analysis of aortic deformation. Through several illustrative cases we demonstrate that this method can be used to measure changes in the aortic wall geometry among patients with stable and enlarging thoracic aortic aneurysm and dissection. Furthermore, VDM results yield observations about the presence, distribution, and rate of aortic wall deformation that are not apparent by routine clinical evaluation. Finally, we show the feasibility of superposing patient-specific VDM results on a 3-dimensional aortic model using color 3D printing and discuss future directions and potential applications for the VDM technique.
Medical image segmentation using analysis of isolable-contour maps (2000)

A common challenge for automated segmentation techniques is differentiation between images of close objects that have similar intensities, whose boundaries are often blurred due to partial-volume effects. We propose a novel approach to segmentation of two-dimensional images, which addresses this challenge. Our method, which we call intrinsic shape for segmentation (ISeg), analyzes isolabel-contour maps to identify coherent regions that correspond to major objects. ISeg generates an isolabel-contour map for an image by multilevel thresholding with a fine partition of the intensity range. ISeg detects object boundaries by comparing the shape of neighboring isolabel contours from the map. ISeg requires only little effort from users; it does not require construction of shape models of target objects. In a formal validation with computed-tomography angiography data, we showed that ISeg was more robust than conventional thresholding, and that ISeg's results were comparable to results of manual tracing.
Active multi-mode-interferometer semiconductoroptical amplifier (2000)

A new type of semiconductor optical amplifier (SOA), consisting of a singlemode waveguide with a 1 × 1 multimode-interferometer (MMI) section, is proposed and experimental results presented. Maintaining single lobed outputs, these new MMI amplifiers show improvements of 2 dB in gain and 5 dB in saturation output compared to regular single-stripe SOAs.
Experimental and Modeling Studies of Metal Halide Catholyte and Cathode Materials to Enable Low-temperature Molten Sodium Batteries. (2021)

Abstract not provided.
Optimizing a Waveguide-Based Sandwich Immunoassay for Tumor Biomarkers: Evaluating Fluorescent Labels and Functional Surfaces (2009)

The sensor team at the Los Alamos National Laboratory has developed a waveguide-based optical biosensor for the detection of biomarkers associated with disease. We have previously demonstrated the application of this technology to the sensitive detection of carcinoembryonic antigen in serum and nipple aspirate fluid from breast cancer patients. In this publication, we report improvements to this technology that will facilitate transition to a point-of-care diagnostic system and/or robust research tool. The first improvement involved replacing phospholipid bilayers used for waveguide functionalization with self-assembled monolayers. These thin films are stable, specific, and robust silane-based surfaces that reduce nonspecific binding and enhance the signal to background ratio. Second, we have explored four different fluorescent labeling paradigms to determine the optimal procedure for use in the assay. Labeling the detector antibody with an organic dye (AlexaFluor 647) in the hinge region allows for unusual signal enhancement with repeat excitation (at 635 nm) in our assay format, thereby facilitating a better signal resolution at lower concentrations of the antigen. We have also labeled the detector antibody with photostable quantum dots through either the amine groups of lysine (Fc, NH) or using a histidine tag in the hinge region of the antibody (Hinge, H). Both labeling strategies allow for acceptable signal resolution, but quantum dots show much greater resistance to photobleaching than organic dyes.
Purification and Characterization of a Recombinant Human Cripto-1 Protein (1998)

Cripto-1 (CR-1) is a novel protein that contains a modified EGF-like motif and that does not directly bind to any of the known erb B type-1 receptor tyrosine kinase receptors. To more clearly define the biological effects of CR-1 and to more adequately compare the structure-function relationships of CR-1 with other members of the EGF family of growth factors, we have expressed a modified, full-length recombinant human CR-1 protein (rhCR-1) in E. coli and have devised a procedure for the solubilization, refolding and purification of a biologically active form of this protein. We have generated the mature form of hCR-1 from computer assisted predictions of potential signal peptide cleavage sites. Expression of the modified rhCR-1 protein in E. coli was limited to the inclusion bodies. The rhCR-1 protein was found to be expressed at high levels in bacterial cells when fused to a histidine-tag sequence. Refolding of rhCR-1 was found to be difficult because of the large number of cysteine residues in the protein which results in protein aggregation. By chemically modifying the cysteine residues in the rhCR-1 protein with 3-trimethylammoniopropyl methanethiosulfonate, additional positive charges have been introduced into the protein by this disulfiding reagent. This modification facilitates solubilization of the protein when rhCR-1 is denatured. The solubilized, denatured protein was then purified by CM cation exchange and C4 reverse phase HPLC chromatography and refolded in a redox buffer. The refolded, modified rhCR-1 protein was found to be biologically active by its ability to inhibit beta-casein expression, to stimulate the tyrosine phosphorylation of Shc and the activation of MAPK and by its capacity to facilitate branching growth of mouse mammary epithelial cells in type I collagen gels.