gebhart/patrepeval huggingface dataset:
Directional genomic hybridization for chromosomal inversion discovery and detection (2013)

Chromosomal rearrangements are a source of structural variation within the genome that figure prominently in human disease, where the importance of translocations and deletions is well recognized. In principle, inversions-reversals in the orientation of DNA sequences within a chromosome-should have similar detrimental potential. However, the study of inversions has been hampered by traditional approaches used for their detection, which are not particularly robust. Even with significant advances in whole genome approaches, changes in the absolute orientation of DNA remain difficult to detect routinely. Consequently, our understanding of inversions is still surprisingly limited, as is our appreciation for their frequency and involvement in human disease. Here, we introduce the directional genomic hybridization methodology of chromatid painting-a whole new way of looking at structural features of the genome-that can be employed with high resolution on a cell-by-cell basis, and demonstrate its basic capabilities for genome-wide discovery and targeted detection of inversions. Bioinformatics enabled development of sequence- and strand-specific directional probe sets, which when coupled with single-stranded hybridization, greatly improved the resolution and ease of inversion detection. We highlight examples of the far-ranging applicability of this cytogenomics-based approach, which include confirmation of the alignment of the human genome database and evidence that individuals themselves share similar sequence directionality, as well as use in comparative and evolutionary studies for any species whose genome has been sequenced. In addition to applications related to basic mechanistic studies, the information obtainable with strand-specific hybridization strategies may ultimately enable novel gene discovery, thereby benefitting the diagnosis and treatment of a variety of human disease states and disorders including cancer, autism, and idiopathic infertility.
A method for using a time interval counter to measure frequency stability (1987)

It is shown how a commercial time interval counter can be used to measure the relative stability of two signals that are offset in frequency and mixed down to a beat note of about 1 Hz. To avoid the dead-time problem, the counter is set up to read the time interval between each beat note upcrossing and the next pulse of a 10 Hz reference pulse train. The actual upcrossing times are recovered by a simple algorithm whose outputs can be used for computing residuals and Allan variance. A noise floor-test yielded a delta f/f Allan deviation of 1.3 times 10 to the minus 9th power/tau relative to the beat frequency.
Mapping Brain Glucose Uptake with Chemical Exchange-Sensitive Spin-Lock Magnetic Resonance Imaging (2014)

Uptake of administered D-glucose (Glc) or 2-deoxy-D-glucose (2DG) has been indirectly mapped through the chemical exchange (CE) between glucose hydroxyl and water protons using CE-dependent saturation transfer (glucoCEST) magnetic resonance imaging (MRI). We propose an alternative technique-on-resonance CE-sensitive spin-lock (CESL) MRI-to enhance responses to glucose changes. Phantom data and simulations suggest higher sensitivity for this 'glucoCESL' technique (versus glucoCEST) in the intermediate CE regime relevant to glucose. Simulations of CESL signals also show insensitivity to B0-fluctuations. Several findings are apparent from in vivo glucoCESL studies of rat brain at 9.4 Tesla with intravenous injections. First, dose-dependent responses are nearly linearly for 0.25-, 0.5-, and 1-g/kg Glc administration (obtained with 12-second temporal resolution), with changes robustly detected for all doses. Second, responses at a matched dose of 1 g/kg are much larger and persist for a longer duration for 2DG versus Glc administration, and are minimal for mannitol as an osmolality control. And third, with similar increases in steady-state blood glucose levels, glucoCESL responses are ∼2.2 times higher for 2DG versus Glc, consistent with their different metabolic properties. Overall, we show that glucoCESL MRI could be a highly sensitive and quantifiable tool for glucose transport and metabolism studies.
Towards the Design of 3D Fiber-Deposited Poly( -caprolactone)/Iron-Doped Hydroxyapatite Nanocomposite Magnetic Scaffolds for Bone Regeneration (2014)

In the past few years, researchers have focused on the design and development of three-dimensional (3D) advanced scaffolds, which offer significant advantages in terms of cell performance. The introduction of magnetic features into scaffold technology could offer innovative opportunities to control cell populations within 3D microenvironments, with the potential to enhance their use in tissue regeneration or in cell-based analysis. In the present study, 3D fully biodegradable and magnetic nanocomposite scaffolds for bone tissue engineering, consisting of a poly(ε-caprolactone) (PCL) matrix reinforced with iron-doped hydroxyapatite (FeHA) nanoparticles, were designed and manufactured using a rapid prototyping technique. The performances of these novel 3D PCL/FeHA scaffolds were assessed through a combination of theoretical evaluation, experimental in vitro analyses and in vivo testing in a rabbit animal model. The results from mechanical com- pression tests were consistent with FEM simulations. The in vitro results showed that the cell growth in the magnetized scaffolds was 2.2-fold greater than that in non-magnetized ones. In vivo experiments further suggested that, after only 4 weeks, the PCL/FeHA scaffolds were completely filled with newly formed bone, proving a good level of histocompatibility. All of the results suggest that the introduction of magnetic features into biocompatible materials may confer significant advantages in terms of 3D cell assembly.
O16.4 Structural similarity of<i>treponema pallidum</i>protein Tp0225 with human toll-like receptor 2 (2019)

<h3>Background</h3> The causative agent of syphilis, <i>Treponema pallidum</i>, is a highly invasive chronic pathogen. Here we used bioinformatics and structural biology to characterize the sole LRR-containing protein in <i>T. pallidum</i>, Tp0225. In other bacterial pathogens, Leucine-Rich Repeat (LRR)-containing proteins contribute to chronicity by mediating attachment, invasion and immune evasion. <h3>Methods</h3> A phylogenetic tree was constructed to determine the evolutionary relationship between Tp0225 and LRR homologs from pathogenic and non-pathogenic treponemes. The size and organization of Tp0225 protein domains were analyzed by comparing them to the domains of the treponemal homologs. For structure determination, the full-length recombinant protein was purified, crystallized, and the three dimensional structure determined using X-ray crystallography. <h3>Results</h3> Bioinformatic analyses showed that Tp0225 has diverged more from non-pathogens compared to pathogens during evolution. The structure of Tp0225 demonstrated that the protein adopts a non-classical LRR fold and contains a hydrophobic pocket on the surface of the structure. This unusual LRR characteristic is similar to the hydrophobic pocket found on the surface of the human Toll-like Receptor 2 (TLR2) LRR domain that recognizes <i>T. pallidum</i> during infection. <h3>Conclusion</h3> We have determined the structure of the only LRR-containing protein in <i>T. pallidum</i> and have shown that it contains an unusual LRR structural feature that is shared with the host innate immune signaling molecule TLR2. This structural mimicry may be involved in subversion of normal host processes during <i>T. pallidum</i> infection. <h3>Disclosure</h3> No significant relationships.
Enzyme-responsive progelator cyclic peptides for minimally invasive delivery to the heart post-myocardial infarction (2019)

Injectable biopolymer hydrogels have gained attention for use as scaffolds to promote cardiac function and prevent negative left ventricular (LV) remodeling post-myocardial infarction (MI). However, most hydrogels tested in preclinical studies are not candidates for minimally invasive catheter delivery due to excess material viscosity, rapid gelation times, and/or concerns regarding hemocompatibility and potential for embolism. We describe a platform technology for progelator materials formulated as sterically constrained cyclic peptides which flow freely for low resistance injection, and rapidly assemble into hydrogels when linearized by disease-associated enzymes. Their utility in vivo is demonstrated by their ability to flow through a syringe and gel at the site of MI in rat models. Additionally, synthetic functionalization enables these materials to flow through a cardiac injection catheter without clogging, without compromising hemocompatibility or cytotoxicity. These studies set the stage for the development of structurally dynamic biomaterials for therapeutic hydrogel delivery to the MI.
Precision Extrusion Deposition With Integrated Assisting Cooling to Fabricate 3D Scaffolds (2010)

As the field of Tissue Engineering advances to its ultimate goal of engineering a fully functional organ, there’s an increase need for enabling technologies and integrated system. Important roles in scaffold guided tissue engineering are the fabrication of extra-cellular matrices (ECM) that have the capabilities to maintain cell growth, cell attachment, and ability to form new tissues. Three-dimensional scaffolds often address multiple mechanical, biological and geometrical design constraints. With advances of technologies in the recent decades, Computer Aided Tissue Engineering (CATE) has much development in solid freeform fabrication (SFF) process, which includes but not limited to the fabrication of tissue scaffolds with precision control. Drexel University patented Precision Extrusion Deposition (PED) device uses computer aided motion and extrusion to precisely fabricate the internal and external architecture, porosity, pore size, and interconnectivity within the scaffold. The high printing resolution, precision, and controllability of the PED allows for closer mimicry of tissues and organs. Literatures have shown that some cells prefer scaffolds built from stiff material; stiff materials typically have a high melting point. Biopolymers with high melting points are difficult to manipulate to fabricate 3D scaffold. With the use of the PED and an integrated Assisting Cooling (AC) device; high melting points of biopolymer should no longer limit the fabrication of 3D scaffold. The AC device is mounted at the nozzle of the PED where the heat from the material delivery chamber of the PED has no influence on the AC fluid temperature. The AC has four cooling points, located north, south, east, and west; this allows for cooling in each direction of motion on a XY plane. AC uses but not limited to nitrogen, compressed air, and water to cool polymer filaments as it is extruded from the PED and builds scaffolds. Scaffolds fabricated from high melting point polymers that use this new integrated component to the PED should illustrate good mechanical properties, structural integrity, and precision of pore sizes and interconnectivity.
Imaging performance of a LaBr<inf>3</inf>-based time-of-flight PET scanner (2008)

There has recently been renewed interest in time-of-flight (TOF) PET due to the availability of fast scintillators that also have high light output and high stopping power, as well as cost-effective fast photomultiplier tubes and stable electronics. Early results with these TOF-PET systems have shown both an improved contrast/noise trade-off and faster convergence compared with reconstructions without TOF information. Simulations have predicted further improvement in imaging performance with better timing resolution. A prototype whole-body PET scanner incorporating Ce-doped LaBr <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">3</inf> crystals and specialized timing circuitry to take advantage of the scintillator’s fast timing characteristics has recently been completed. The intrinsic performance of the scanner has been measured. The average energy resolution over all crystals is 6.5%, and the system timing resolution is 375 ps. The scatter fraction for 20-, 27-, and 35-cm diameter cylinders is 21, 27, and 32%, respectively, for a 485-keV lower energy threshold. The average spatial resolution is 5.8 mm at 1 cm and 6.5 mm at 10 cm. Resolution modeling has been incorporated into the list-mode TOF iterative algorithm. Simulation studies were carried out to measure the relative impact of timing resolution, energy resolution and lower energy threshold, and spatial resolution modeling on TOF-PET imaging performance as characterized by the contrast/noise trade-off. It was found that improved timing resolution leads to faster, more uniform convergence with less variability in quantification as a function of either radial position or local activity environment. Better energy resolution allows for the use of a tighter energy window, which leads to fewer accepted scatter events and improved quantitative accuracy. Resolution modeling improves contrast recovery at the cost of slower convergence; further work is needed to define an accurate model of the point spread function for the LaBr <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">3</inf> system. The superior timing and energy resolutions appear to mitigate the loss of spatial resolution that arises from the lower stopping power of the crystal.
INDUCTION OF ATL-LIKE LYMPHOPROLIFERATIVE DISEASE AND ITS PREVENTION BY ADOPTIVE IMMUNOTHERAPY IN T-CELL DEFICIENT NUDE RATS INOCULATED WITH SYNGENIC HTLV-I-IMMORTALIZED CELLS (1999)

SP-09 Human T-cell leukemia virus type I (HTLV-I) has been shown to be the oncogenic agent of adult T cell leukemia (ATL), but the in vivo mechanism by which the virus causes the malignant transformation is largely unknown. In this study, we developed a rat model system in which ATL-like disease was reproducibly observed, following inoculation of various rat HTLV-I immortalized cell lines. When we inoculated previously established cell lines, some of them developed systemic multiple tumors in adult nude (nu/nu) rats. FPM1 cells, newly established from a hetero (nu/+) rat syngenic to nude rats, caused transient tumors only at the injection site in adult nu/nu rats, but could progressively grow in new born nu/nu rats and metastasize in lymph nodes. The derivative cell line (FPM1-V1AX) serially passed through newborn nu/nu rats acquired the potency to grow in adult nu/nu rats. These results indicated that only some with additional changes but not all the in vitro HTLV-I immortalized cell lines possessed in vivo tumorigenicity. Using the syngenic system, we further showed the inhibition of tumor development by transferring splenic T cells from immunized rats, suggesting the involvement of T cells in the regression of tumor. This nude rat model of human ATL will be useful for further investigation of both leukemogenesis and anti-tumor immune responses in HTLV-I infection.
Pyrimidines. 17. Novel pyrimidine to pyridine transformation reaction. One-step synthesis of pyrido[2,3-d]pyrimidines (1981)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTPyrimidines. 17. Novel pyrimidine to pyridine transformation reaction. One-step synthesis of pyrido[2,3-d]pyrimidinesKosaku Hirota, Yukio Kitade, Shigeo Senda, Michael J. Halat, Kyoichi A. Watanabe, and Jack J. FoxCite this: J. Org. Chem. 1981, 46, 5, 846–851Publication Date (Print):February 1, 1981Publication History Published online1 May 2002Published inissue 1 February 1981https://pubs.acs.org/doi/10.1021/jo00318a004https://doi.org/10.1021/jo00318a004research-articleACS PublicationsRequest reuse permissionsArticle Views551Altmetric-Citations41LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
2‐Substituted 6‐(Het)aryl‐7‐deazapurine Ribonucleosides: Synthesis, Inhibition of Adenosine Kinases, and Antimycobacterial Activity (2015)

A series of 6-(hetero)aryl- or 6-methyl-7-deazapurine ribonucleosides bearing a substituent at position 2 (Cl, F, NH2, or CH3) were prepared by cross-coupling reactions at position 6 and functional group transformations at position 2. Cytostatic, antiviral, and antimicrobial activity assays were performed. The title compounds were observed to be potent and selective inhibitors of Mycobacterium tuberculosis adenosine kinase (ADK), but not human ADK; moreover, they were found to be non-cytotoxic. The antimycobacterial activities against M. tuberculosis, however, were only moderate. The reason for this could be due to either poor uptake through the cell wall or to parallel biosynthesis of adenosine monophosphate by the salvage pathway.
An analysis of heat removal during cryogen spray cooling and effects of simultaneous airflow application (2001)

Background and Objective Cryogen spray cooling (CSC) is a method used to protect the epidermis from non-specific thermal injury that may occur as a result of various dermatological laser procedures. However, better understanding of cryogen deposition and skin thermal response to CSC is needed to optimize the technique. Study Design/Materials and Methods Temperature measurements and video imaging were carried out on an epoxy phantom as well as human skin during CSC with and without simultaneous application of airflow which was intended to accelerate cryogen evaporation from the substrate surface. An inverse thermal conduction model was used to estimate heat flux and total heat removed. Results Lifetime of the cryogen film deposited on the surface of skin and epoxy phantom lasted several hundred milliseconds beyond the spurt, but could be reduced to the spurt duration by application of airflow. Values over 100 J/cm3 were estimated for volumetric heat removed from the epidermis using CSC. Conclusions “Film cooling” instead of “evaporative cooling” appears to be the dominant mode of CSC on skin. Estimated values of heat removed from the epidermis suggest that a cryogen spurt as long as 200 milliseconds is required to counteract heat generated by high laser fluences (e.g., in treatment of port wine stains) in patients with high concentration of epidermal melanin. Additional cooling beyond spurt termination can be avoided by simultaneous application of airflow, although it is unclear at the moment if avoiding the additional cooling would be beneficial in the actual clinical situation. Lasers Surg. Med. 39:477–486, 2001. © 2001 Wiley-Liss, Inc.
Mechanisms of protective immunity against <i>Schistosoma mansoni</i> infection in mice vaccinated with irradiated cercariae. II. Analysis of immunity in hosts deficient in T lymphocytes, B lymphocytes, or complement. (1982)

Laboratory mice with genetic or induced immunodeficiencies were vaccinated with irradiated cercariae of Schistosoma mansoni and assayed 4 wk later for their resistance to challenge infection. Athymic nude mice failed to develop immunity to challenge or detectable antibody responses to schistosomula, whereas heterozygote (nu/+) controls and nude mice with thymus grafts displayed highly significant levels of resistance and anti-schistosomulum antibody. Similarly, no resistance or antibody production as observed in vaccinated mice that had been made deficient in B lymphocytes by the injection of anti-mu-chain antisera from birth. In contrast, normal levels of vaccine-induced resistance were observed in mice genetically deficient in the fifth component of complement (C5) and in mice decomplemented before challenge by treatment with cobra venom factor. These results indicate that the resistance to challenge infection induced by irradiated cercariae is both thymus and B lymphocyte dependent and therefore is likely to result from specific immune responses directed against schistosome worms. The data also argue against a role for complement in the effector mechanism of vaccine-induced immunity.
Platinum vapor deposition surface‐assisted laser desorption/ionization for imaging mass spectrometry of small molecules (2012)

A solvent-free approach involving the direct deposition of Pt on samples (SALDI-IMS) is effective for the analysis of inkjet-printed papers and various analytes separated by TLC. This method would be useful in imaging analyses of various insulating materials such as polymers and biological materials.
Restoration of images scanned in the presence of vibrations (1996)

Images scanned in the presence of mechanical vibration are subject to artifacts such as brightness fluctuation and geometric warping. The goal of the present study is to characterize these distortions and develop a restoration algorithm to invert them, hence producing an output digital image consistent with a scanner operating under ideal uniform motion conditions. The image restoration algorithm described in this paper makes use of the instantaneous velocity of the linear sensor array to reconstruct an underlying piecewise constant or piecewise linear model of the image irradiance profile. That reconstructed image is then suitable for resampling under ideal scanning conditions to produce the restored output digital image. We demonstrate the algorithm on simulated scanned imagery with typical operating parameters.
Illuminating Illumination (2001)

We introduce an active imaging method to measure scene illumination. The system implementation is divided into four steps. First, the system acquires two images: one is an ordinary image of the scene under ambient light and the other is a corresponding image in which light from the camera flash is added to the scene. Second, the image pair is analyzed to obtain an image that represents the scene as if it had been illuminated by the flash alone. Third, the flash-only image is used to estimate object reflectance functions. Fourth, using the estimated reflectance functions, the ambient illumination spectral power distribution is estimated. We present results that evaluate the method's stability with respect to changes in the mean reflectance function of the scene. Finally, we discuss limitations of the current implementation and alternative implementations.