gebhart/patrepeval huggingface dataset:
Heart Protection Using a New Approach - Antisense to Angiotensin Converting Enzyme Mrna (2000)

P200 Introduction. Angiotensin converting enzyme (ACE), plays a major role in many cardiovascular pathophysiological conditions, such as hypertension, heart failure and myocardial ischemia. Currently used ACE inhibitors have some adverse effects and non-compliance problem. Therefore, our lab has been developing an antisense approach to inhibit the renin-angiotensin system at the gene expression level. The present study had three aims: 1. Design antisense oligodeoxynucleotide (AS-ODN) directed at ACE mRNA 2. Check tissue distribution of AS after iv injection 3. Test AS for heart protection in ischemia- reperfusion injury Methods. Epifluorescent and confocal laser-scanning microscopy, immunohistochemistry, Western blotting. Animals : mice, males, 20 g and Sprague-Dawley rats, males, 200-250 g. AS 5’ -ATTTCGTGGTGGG-3’ , inverted control (INV) 5’ -GGGTGGTGCTTTA-3’, phosphorothioates mixed with liposomes and injected iv 0.04 mg/mouse and 0.2 mg/rat. Captopril dose was 5 mg/kg. Isolated perfused heart function recordings : coronary perfusion pressure (CPP), left ventricular end-diastolic (LVEDP) and systolic pressures (LVSP). Results. Based on the rat ACE cDNA sequence, the AS was designed as 13-mer directed to the second zinc-binding domain (2998-3010 bp). Tissue distribution of phosphorothioated, fluorescein isothiocyanate (FITC)-labeled AS, 4h after iv injection, showed its presence in the lung, spleen, liver and heart, but absence in the brain. Immunostaining of the parallel heart slices with anti sarcomeric alpha-actinin antibody indicated AS localization within cardiomyocytes. ACE AS injected iv to the rats 24 h before excising the heart, which was then subjected to 25 min ischemia and 30 min reperfusion, preserved heart function. Increase in CPP and LVEDP during reperfusion was attenuated by AS as compared to INV or saline treatment (n=8 in each group, p&lt;0.05). Moreover, ACE protein was not upregulated, as it was in the captopril-treated group. Conclusion. ACE AS is taken up by the heart tissue and provides cardioprotection by effectively preventing myocardial dysfunction caused by ischemia-reperfusion injury.
The use of solid-state lasers to replace traditional UV photon sources in medical device manufacturing (1997)

Traditional Excimer Laser UV photon sources are used in the manufacture of many medical devices including angioplasty balloons, catheters and other disposable devices made from plastics. These sources provide fairly stable, high energy radiation with reasonably short pulse lengths (about 20 ns) that are ideal for processing materials with high UV absorptions cleanly and economically. There are, however, several drawbacks to using excimer lasers in production including the capital and operating costs, the poor beam utilization efficiency of many hole drilling applications, the physical size and the relatively low pulse repetition rates (normally only a few hundred Hz). New diode pumped solid state lasers, incorporating efficient non-linear conversion to the ultraviolet, provide an attractive alternative to traditional sources and minimize some of the difficulties mentioned above. Compact systems with pulse-to-pulse energy variations of a few percent and repetition rates of several tens of kHz are now available which will both replace excimers in some application areas and open new application areas. This paper will discuss both the new laser sources and their direct application to the manufacture of medical devices.
Identification of an HLA-A*0201-restricted epitopic peptide from human dystrophin: application in duchenne muscular dystrophy gene therapy (2003)

Dystrophin-based gene therapy treatments aimed at correcting the Duchenne muscular dystrophy phenotype require stable expression of normal dystrophin (DYST) protein in myocytes without immune responses, which would compromise long-term expression. To predict cytotoxic T-cell-mediated responses elicited by transgenes, we used here H-2-negative HLA-A*0201 transgenic mice and identified human DYST epitopes, which elicit HLA-A*0201-restricted cytotoxic T cell activities. Among a series of eight peptides predicted from the human DYST sequence, not shared with the endogenous mouse DYST sequence, four of them were able to bind to HLA-A*0201 molecules and to induce cytotoxic T lymphocyte (CTL) responses. After human DYST DNA transfer in muscle of HLA-A*0201 mice, only the human DYST1281 epitope, located in the spectrin-like repeat 9 domain, induced strong CD8(+) CTL responses. Using the corresponding human DYST1281 peptide/HLA-A*0201 tetramer, we detected human DYST1281-specific CD8(+) T cells in peripheral lymphoid organs and blood of HLA-A*0201 mice injected with human DYST DNA. Our results demonstrate that muscle injection with human DYST DNA systematically triggers CTL responses against this HLA-A*0201-restricted human DYST1281 peptide, which is present in long human DYST isoforms. Identification of such immunodominant human DYST epitopes and use of peptide/HLA tetramers will allow the immunomonitoring of CTL responses in HLA-phenotyped Duchenne muscular dystrophy patients undergoing gene therapy. Finally, the knowledge of HLA-A*0201-restricted human DYST peptides will be of importance to test, in mouse models, new immunomodulatory interventions allowing long-term engraftment of human dystrophin.
Unprecedented Sequence Control and Sequence‐Driven Properties in a Series of AB‐Alternating Copolymers Consisting Solely of Acrylamide Units (2020)

Abstract Herein, we report a method to synthesize a series of alternating copolymers that consist exclusively of acrylamide units. Crucial to realizing this polymer synthesis is the design of a divinyl monomer that contains acrylate and acrylamide moieties connected by two activated ester bonds. This design, which is based on the reactivity ratio of the embedded vinyl groups, allows a “selective” cyclopolymerization, wherein the intramolecular and intermolecular propagation are repeated alternately under dilute conditions. The addition of an amine to the resulting cyclopolymers afforded two different acryl amide units, i.e., an amine‐substituted acryl amide and a 2‐hydroxy‐ethyl‐substituted acryl amide in alternating sequence. Using this method, we could furnish ten types of alternating copolymers; some of these exhibit unique properties in solution and in the bulk, which are different from those of the corresponding random copolymers, and we attributed the differences to the alternating sequence.
Influence of acute selective endothelin-receptor-A blockade on renal hemodynamics in a rat model of chronic allograft rejection (2003)

Abstract We have recently demonstrated up-regulation of renal endothelin (ET) synthesis in a rat model of chronic renal allograft rejection. Treatment with a selective ET-A receptor antagonist improved survival and reduced functional and morphological kidney damage. However, the underlying mechanisms have not yet been elucidated, as ET exhibits both hemodynamic and inflammatory properties. Therefore, in the present study we investigated acute hemodynamic effects of the selective ET-A receptor antagonist LU 302146 (LU) on chronic renal allograft rejection in rats. Experiments were performed in the Fisher-to-Lewis model of chronic renal allograft rejection. Lewis-to-Lewis isografts served as controls. After 2, 12, and 24 weeks, hemodynamic measurements were performed on anesthetized animals. Measurement of mean arterial pressure (MAP) was performed via a catheter in the femoral artery. Renal blood flow (RBF) was measured by an ultrasonic flow probe placed around the renal transplant artery. Medulla blood flow (MBF) and cortex blood flow (CBF) were determined with laser Doppler probes. Hemodynamic response upon intravenous bolus injection of LU (50 mg/kg) was investigated. The application of LU was followed by a decline in MAP that reached statistical significance only in isografts (ISOs) after 12 weeks and allografts (ALLOs) after 24 weeks. RBF slightly decreased in all groups; however, without reaching statistical significance. MBF showed a small incrase in ALLO12 and ALLO24 whereas CBF slightly decreased in all groups. Acute ET-A receptor blockade does not induce important hemodynamic effects in kidneys undergoing chronic rejection. The lack of response to ET-A receptor blockade suggests that the beneficial effect of ET receptor antagonists in this model is likely to be due to improvement of renal morphology.
Nuclear compartmentalization of TERT mRNA and TUG1 lncRNA transcripts is driven by intron retention: implications for RNA-directed therapies (2020)

Abstract Numerous global connections have been made between splicing and other layers of gene regulation, including the spatial partitioning of the transcriptome in the cell. Yet, there has been surprisingly little analysis of the spatio-temporal regulation of individual protein-coding and non-coding RNA molecules in single cells. Here we address how intron retention influences the spatio-temporal dynamics of transcripts from two clinically relevant genes: TERT (Telomerase Reverse Transcriptase) pre-mRNA and TUG1 (Taurine-Upregulated Gene 1) lncRNA. Single molecule RNA FISH revealed that nuclear TERT transcripts uniformly and robustly retain two specific introns whose splicing occurs during mitosis. In contrast, TUG1 has a bimodal distribution of fully spliced cytoplasmic and intron-retained nuclear transcripts. We further test the functionality of intron-retention events using RNA-targeting thiomorpholino antisense oligonucleotides to block intron excision. We show that intron retention is the driving force for the nuclear compartmentalization of these RNAs. For both RNAs, altering this splicing-driven subcellular distribution had significant effects on cell growth. Together, these findings show that stable retention of specific introns can orchestrate spatial compartmentalization of RNAs within the cell; this process reveals new targets for RNA-based therapies.
Cross-species blastocyst chimerism between nonhuman primates using iPSCs (2019)

Summary Through the production of chimeric animals, induced pluripotent stem cells (iPSCs) can generate personalized organs with diverse applications for both basic research and translational medicine. This concept was first validated in rodents by forming a rat pancreas in mice and vice versa. However, the potential use of human iPSCs to generate xenogenic organs in other species is technically and ethically difficult. Recognizing these concerns, we explored the generation of chimeric nonhuman primates (NHP) embryos, by injecting either chimpanzee or pig-tailed macaque iPSCs into rhesus macaque embryos. We first derived iPSCs from chimpanzees and pig-tailed macaques. We found that the chimpanzee iPSCs mixed well with human iPSCs during in vitro co-culture and differentiation. The differentiation of mixed human and chimpanzee iPSCs formed functioning cardiomyocyte layers in vitro, whereas human or chimpanzee iPSC mixed with pig-tailed macaque or mouse cells do not; these results indicate that chimpanzee and human cells are closely related in function. Considering the ethical aspects of injecting human iPSCs into nonhuman primate blastocysts, we tested whether chimpanzee iPSCs injected into 99 macaque 5-day-old embryos formed cross-species chimeras two days after injection. Strikingly, the chimpanzee iPSCs survived, proliferated and integrated near the inner cell mass (ICM) of rhesus macaque embryos. These findings highlight the broad potential of primate iPSCs in forming cross-species chimeras beyond rodents and provides a foundational basis for organ generation using human iPSCs.
Mechanochemically Induced sp3-Bond-Associated Reconstruction of Single-Wall Carbon Nanohorns (2008)

Single-wall carbon nanohorns (SWCNHs) and partially oxidized SWCNHs (ox-SWCNHs) were mechanochemically treated for the elucidation of their unique chemical bonding state. The mechanochemical treatment promoted the transformation from sp2 to sp3 bonding from XPS, leading to an increase and decrease in the micropore volume for SWCNHs and ox-SWCNHs, respectively. The changes in the micropore volume and the electrical conductivity responses on CO2 adsorption indicate the occurrence of tubulite-to-tubulite reconstruction in SWCNH through unstable sp3 bonding.
Adenosine A2A Receptor Ligand Binding Experiments by Using Real-time Single-cell FRET (2014)

We designed a fluorescence resonance energy transfer (FRET)-based approach to study the ligand binding constants of the adenosine A2A receptor (A2AR). Our assay is based in the interaction of a fluorescent A2AR agonist ligand (MRS5424) with an A2AR tagged with the cyan fluorescent protein (CFP) at the N-terminus (i.e. A2ARCFP) and expressed in living cells. Thus, upon fast superfusion of the A2ARCFP expressing cells with MRS5424, the ligand-receptor interaction is determined by single-cell FRET in a real-time mode. Accordingly, our approach allowed immediate ‘real-time’ readout of the ligand-receptor interaction, thus allowing kinetic binding experiments, a feature impossible to achieve using conventional radioisotope-labelled ligands. In addition, since our assay permitted the visual confirmation of receptor localization it also allowed localized saturation binding experiments.
ChemInform Abstract: New Cytotoxic Sesterterpenes from the New Caledonian Marine Sponge Petrosaspongia nigra (Bergquist) (1997)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Use of a composite nonlinear model including microbubbles and tissue to examine effects for ultrasonic propagation and backscatter in complex tissues - nonlinear ultrasonic waves in composite tissues (2005)

Several numerical modeling studies have examined nonlinear propagation of ultrasound in tissue (KZK equation). Similarly, other investigations have studied nonlinear backscatter characteristics from ultrasound contrast microbubbles (RP equation). However, very few reports on combined tissue-bubble models are available, especially in the area of nonlinear contribution of microbubbles to ultrasonic propagation and backscatter in complex tissue where both blood vessels and surrounding soft tissue are incorporated. Results from such studies should contribute further to the continuing optimization of harmonic imaging techniques. In this study, the well-known KZK equation is adapted to include tissue and blood vessels with microbubbles. A composite approach utilizing the equivalent nonlinearity and attenuation parameters for the blood vessel with varying amount of contrast (volume fraction of bubbles to blood: 10/sup -8/ to 10/sup -6/) provides the resultant equation which is then solved using a time-domain finite difference technique. Harmonic analysis of tissue propagation shows that the microbubbles induce significant nonlinearity in the propagating wave, which influences both harmonic generation and waveform distortion by causing spatial shifts of the harmonic focal points (2/sup nd/ and 3/sup rd/ harmonics) and production of higher amplitude harmonic wave components. Wave-diffraction patterns of the multi-harmonic components varied mainly as a function of bubble concentration within the local blood vessel. These results provide a means for understanding harmonic effects in a realistic composite tissue-blood vessel model and should provide pathways to improve signal-to-noise ratio in harmonic imaging.
Modeling and performances of a polarization active imager at <inline-formula>λ=806 <roman>nm</roman></inline-formula> (2000)

We present the modeling and the performance of a polarization active imager at l5806 nm. The device operates in a monostatic configuration, using a semiconductor laser to illuminate the target and a telescope to create the image on a CCD matrix. Dual images (intensity and polarization degree) of different scenes are obtained by a new method (only two images acquired) and analyzed, showing the experimental validation of this concept. An application of this active imager to the detection of a target buried in the background (same reflectivity but different polarization degree) is proposed. Field experiment results are reported.
Minimum Rail Height and Design Impact Load for Longitudinal Barriers that Meet Test Level 4 of Manual for Assessing Safety Hardware (2012)

In 2009, the Manual for Assessing Safety Hardware (MASH) was adopted as an updated replacement of NCHRP Report 350. Under MASH, the impact severity of Test Level 4 (TL-4) (Test 4–12) was increased by 56%. Test vehicle mass was increased from 17,640 to 22,050 lb. Impact speed was increased from 50 to 56 mph. Although this is a significant increase in the amount of lateral energy imparted to the barrier, the 54-kip design impact load currently suggested by the AASHTO load and resistance factor design (LRFD) bridge specifications has not been updated to meet MASH TL-4 requirements. Similarly, the AASHTO LRFD specifications require all TL-4 railings to have a minimum height of 32 in. However, because of the increase in test vehicle mass and impact velocity under MASH, the minimum height for TL-4 railings is expected to be greater than 32 in. This height was verified by a recent unsuccessful MASH Test 4–12 of a New Jersey profile rigid concrete barrier 32 in. tall. The research presented in this paper used finite element analysis and subsequent crash testing to determine the minimum rail height for MASH TL-4 impact conditions. The researchers also determined the appropriate lateral impact design load for use with AASHTO LRFD bridge specifications for the design of TL-4 bridge rails.
Cellular Factors Required for Lassa Virus Budding (2006)

It is known that Lassa virus Z protein is sufficient for the release of virus-like particles (VLPs) and that it has two L domains, PTAP and PPPY, in its C terminus. However, little is known about the cellular factor for Lassa virus budding. We examined which cellular factors are used in Lassa virus Z budding. We demonstrated that Lassa Z protein efficiently produces VLPs and uses cellular factors, Vps4A, Vps4B, and Tsg101, in budding, suggesting that Lassa virus budding uses the multivesicular body pathway functionally. Our data may provide a clue to develop an effective antiviral strategy for Lassa virus.
A novel web-based tool for risk quantification and objectification of treatment of renal cell carcinoma. (2011)

382 Background: Despite the development of treatment guidelines, the management of renal cell carcinoma (RCC) remains overly subjective. Nomograms and statistical algorithms promise more objective decision making by patients and physicians by quantifying risk. Unfortunately, these tools remain underutilized in daily clinical practice because they are both cumbersome and time-consuming. We sought to create a novel website where all the available and relevant nomograms for RCC could be easily accessible for patients and practitioners, minimizing the subjectivity associated with clinical risk stratification and decision-making. Methods: The existing literature was reviewed to identify published nomograms relevant to RCC. Nomograms were grouped by defining characteristics (preoperative versus postoperative predictive models, predictive models for metastatic disease, etc). Additional operationalized models included staging tools, surveillance models and cancer statistics. Nomograms were selected based on predictive accuracy, applicability, and ability to objectify risk stratification. Only nomograms with an AUC of greater than 0.7 were operationalized. The times required to extract clinical metrics for four hypothetical clinical scenarios were compared between the original paper version and our web-based model. Results: www.cancernomograms.com organizes and operationalizes interactive predictive models for RCC for both physicians and patients. Each model was developed as an independent software program and deployed as an interactive flash object embedded in an HTML page allowing point of care risk calculation. In an initial sample of 15 subjects, the website decreased nomogram metric output from minutes to seconds, proving that utilization of a computer-based platform for these nomograms is faster (p=0.0003). Conclusions: www.cancernomograms.com is a novel website that allows point of care risk quantification and objectified decision making using published statistical models. This web tool may help improve physician and patient communication and clinical care. No significant financial relationships to disclose.
Quantitative and qualitative retinal microvascular characteristics and blood pressure (2011)

Elevated blood pressure is associated with a spectrum of quantitative and qualitative retinal vascular signs, with the number of signs increasing with higher blood pressure levels.
Barriers to adoption of biological control agents and biological pesticides (2008)

According to the Biopesticide, Pollution, Prevention Division (BPPD) at the US Environmental Protection Agency (EPA), which registers biological pesticides for sale, biological pesticides or biopesticides are certain types of pesticides derived from such natural materials as animals, plants, bacteria and certain minerals. Biopesticides fall into three major classes: microbial pesticides, plant-incorporated-protectants (PIPs) or biochemical pesticides.
Exceptional nexus with a hybrid topological invariant (2020)

Branch-point singularities known as exceptional points (EPs), which carry a nonzero topological charge, can emerge in non-Hermitian systems. We demonstrate with both theory and acoustic experiments an "exceptional nexus" (EX), which is not only a higher-order EP but also the cusp singularity of multiple exceptional arcs (EAs). Because the parameter space is segmented by the EAs, the EX possesses a hybrid topological invariant (HTI), which consists of distinct winding numbers associated with Berry phases accumulated by cyclic paths on different complex planes. The HTI is experimentally characterized by measuring the critical behaviors of the wave functions. Our findings constitute a major advance in the fundamental understanding of non-Hermitian systems and their topology, possibly opening new avenues for applications.
string2string: A Modern Python Library for String-to-String Algorithms (2023)

We introduce string2string, an open-source library that offers a comprehensive suite of efficient algorithms for a broad range of string-to-string problems. It includes traditional algorithmic solutions as well as recent advanced neural approaches to tackle various problems in string alignment, distance measurement, lexical and semantic search, and similarity analysis -- along with several helpful visualization tools and metrics to facilitate the interpretation and analysis of these methods. Notable algorithms featured in the library include the Smith-Waterman algorithm for pairwise local alignment, the Hirschberg algorithm for global alignment, the Wagner-Fisher algorithm for edit distance, BARTScore and BERTScore for similarity analysis, the Knuth-Morris-Pratt algorithm for lexical search, and Faiss for semantic search. Besides, it wraps existing efficient and widely-used implementations of certain frameworks and metrics, such as sacreBLEU and ROUGE, whenever it is appropriate and suitable. Overall, the library aims to provide extensive coverage and increased flexibility in comparison to existing libraries for strings. It can be used for many downstream applications, tasks, and problems in natural-language processing, bioinformatics, and computational social sciences. It is implemented in Python, easily installable via pip, and accessible through a simple API. Source code, documentation, and tutorials are all available on our GitHub page: https://github.com/stanfordnlp/string2string.