gebhart/patrepeval huggingface dataset:
Oligo(2′‐O‐methyl)ribonucleotides Effective probes for duplex DNA (1992)

To find novel probes for duplex DNA, we prepared four types of triplexes containing a homopurine-homopyrimidine 15-mer duplex DNA, and examined their thermal stabilities (Tm values). The single strand used for triplex formation were a DNA 15-mer having a defined C-T mixed sequence, and its sugar-modified analogs, namely 2'-fluoro DNA, RNA, and 2'-O-methyl RNA. The 2'-O-methyl RNA and the RNA-containing triplexes were similar in their enhanced stabilities at pH 6.1 and, amongst the four triplexes, the 2'-O-methyl was the most stable at pH 5.0. Furthermore, an experiment using a 34-mer duplex DNA suggested that the 2'-O-methyl RNA-triplex was destabilized, mostly as a result of the incorporation of a mismatched triplet, as compared to the DNA triplex counterpart. Thus, 2'-O-methyl RNA can serve as an effective probe for duplex DNA.
Real-Time Imaging of Electrical Signals with an Infrared FDA-Approved Dye (2014)

Clinical methods used to assess the electrical activity of excitable cells are often limited by their poor spatial resolution or their invasiveness. One promising solution to this problem is to optically measure membrane potential using a voltage-sensitive dye, but thus far, none of these dyes have been available for human use. Here we report that indocyanine green (ICG), an infrared fluorescent dye with FDA approval as an intravenously administered contrast agent, is voltage-sensitive. The fluorescence of ICG can follow action potentials in artificial neurons and cultured rat neurons and cardiomyocytes. ICG also visualized electrical activity induced in living explants of rat brain. In humans, ICG labels excitable cells and is routinely visualized transdermally with high spatial resolution. As an infrared voltage-sensitive dye with a low toxicity profile that can be readily imaged in deep tissues, ICG may have significant utility for clinical and basic research applications previously intractable for potentiometric dyes.
Capture of Escherichia coli O157:H7 Using Immunomagnetic Beads of Different Size and Antibody Conjugating Chemistry (2009)

Immunomagnetic beads (IMB) were synthesized using anti-Escherichia coli O157 antibodies and magnetic beads of two different sizes (1 μm and 2.6 to 2.8 μm) that contained a streptavidin coating, activated carboxyl groups or tosylated surfaces. The synthesized IMB, together with a commercially available IMB, were used to capture different strains of E. coli O157:H7 and E. coli O157:NM. The E. coli capture was measured by the time resolved fluorescence (TRF) intensity using a sandwich assay which we have previously demonstrated of having a sensitivity of 1 CFU/g after 4.5 hour enrichment [1]. The analyses of measured TRF intensity and determined antibody surface concentration indicated that larger beads provided higher response signals than smaller beads and were more effective in capturing the target of interest in pure culture and ground beef. In addition, while each type of IMB showed different favorable capture of E. coli O157:H7, streptavidin-coated IMB elicited the highest response, on average. Streptavidin-coated IMB also provided an economic benefit, costing less than $0.50 per assay. The results could be used to guide the proper choice of IMB for applications in developing detection processes for E. coli O157:H7.
A novel Sin Nombre virus DNA vaccine and its inclusion in a candidate pan-hantavirus vaccine against hantavirus pulmonary syndrome (HPS) and hemorrhagic fever with renal syndrome (HFRS) (2013)

Sin Nombre virus (SNV; family Bunyaviridae, genus Hantavirus) causes a hemorrhagic fever known as hantavirus pulmonary syndrome (HPS) in North America. There have been approximately 200 fatal cases of HPS in the United States since 1993, predominantly in healthy working-age males (case fatality rate 35%). There are no FDA-approved vaccines or drugs to prevent or treat HPS. Previously, we reported that hantavirus vaccines based on the full-length M gene segment of Andes virus (ANDV) for HPS in South America, and Hantaan virus (HTNV) and Puumala virus (PUUV) for hemorrhagic fever with renal syndrome (HFRS) in Eurasia, all elicited high-titer neutralizing antibodies in animal models. HFRS is more prevalent than HPS (>20,000 cases per year) but less pathogenic (case fatality rate 1-15%). Here, we report the construction and testing of a SNV full-length M gene-based DNA vaccine to prevent HPS. Rabbits vaccinated with the SNV DNA vaccine by muscle electroporation (mEP) developed high titers of neutralizing antibodies. Furthermore, hamsters vaccinated three times with the SNV DNA vaccine using a gene gun were completely protected against SNV infection. This is the first vaccine of any kind that specifically elicits high-titer neutralizing antibodies against SNV. To test the possibility of producing a pan-hantavirus vaccine, rabbits were vaccinated by mEP with an HPS mix (ANDV and SNV plasmids), or HFRS mix (HTNV and PUUV plasmids), or HPS/HFRS mix (all four plasmids). The HPS mix and HFRS mix elicited neutralizing antibodies predominantly against ANDV/SNV and HTNV/PUUV, respectively. Furthermore, the HPS/HFRS mix elicited neutralizing antibodies against all four viruses. These findings demonstrate a pan-hantavirus vaccine using a mixed-plasmid DNA vaccine approach is feasible and warrants further development.
Advances in molecular diagnostics of myeloproliferative disorders (2007)

Incremental advances in the molecular pathogenesis of myeloproliferative disorders (MPDs) have had a substantial impact on clinical practice in terms of both diagnosis and treatment. An array of novel molecular methods are being developed and integrated into the current battery of tests for diagnosis and monitoring of treatment response. Primarily, subjective clinico-histologic approaches to diagnosis are being replaced by more objective semimolecular diagnostic algorithms. Furthermore, identification of disease-specific molecular markers has facilitated the development of small-molecule drugs for targeted therapy. This review provides an overview of MPDs with emphasis on molecular diagnostic tests and their incorporation into contemporary diagnostic and therapeutic algorithms.
Emerging gene editing strategies for Duchenne muscular dystrophy targeting stem cells (2014)

The progressive loss of muscle mass characteristic of many muscular dystrophies impairs the efficacy of most of the gene and molecular therapies currently being pursued for the treatment of those disorders. It is becoming increasingly evident that a therapeutic application, to be effective, needs to target not only mature myofibers, but also muscle progenitors cells or muscle stem cells able to form new muscle tissue and to restore myofibers lost as the result of the diseases or during normal homeostasis so as to guarantee effective and lost lasting effects. Correction of the genetic defect using oligodeoxynucleotides (ODNs) or engineered nucleases holds great potential for the treatment of many of the musculoskeletal disorders. The encouraging results obtained by studying in vitro systems and model organisms have set the groundwork for what is likely to become an emerging field in the area of molecular and regenerative medicine. Furthermore, the ability to isolate and expand from patients various types of muscle progenitor cells capable of committing to the myogenic lineage provides the opportunity to establish cell lines that can be used for transplantation following ex vivo manipulation and expansion. The purpose of this article is to provide a perspective on approaches aimed at correcting the genetic defect using gene editing strategies and currently under development for the treatment of Duchenne muscular dystrophy (DMD), the most sever of the neuromuscular disorders. Emphasis will be placed on describing the potential of using the patient own stem cell as source of transplantation and the challenges that gene editing technologies face in the field of regenerative biology.
Klotho Gene Delivery Prevents the Progression of Spontaneous Hypertension and Renal Damage (2009)

Klotho is a recently discovered antiaging gene. The objective of this study was to test the hypothesis that klotho gene delivery attenuates the progression of spontaneous hypertension and renal damage in spontaneous hypertensive rats (SHRs). An adeno-associated virus (AAV) carrying mouse klotho full-length cDNA (AAV.mKL) was constructed for in vivo expression of klotho. Four groups of male SHRs and 1 group of sex- and age-matched Wistar-Kyoto rats (5 rats per group) were used. Blood pressure was measured twice in all of the animals before gene delivery. Four groups of SHRs received an IV injection of AAV.mKL, AAV.LacZ, AAV.GFP, and PBS, respectively. The Wistar-Kyoto group received PBS and served as a control. AAV.mKL stopped the further increase in blood pressure in SHRs, whereas blood pressures continued to increase in other SHR groups. One single dose of AAV.mKL prevented the progression of spontaneous hypertension for at least 12 weeks (length of the study). Klotho expression and production were suppressed in SHRs, which were reverted by AAV.mKL. AAV.mKL increased plasma interleukin 10 levels but decreased Nox2 expression, NADPH oxidase activity, and superoxide production in kidneys and aortas in SHRs. AAV.mKL abolished renal tubular atrophy and dilation, tubular deposition of proteinaceous material, glomerular collapse, and collagen deposition seen in SHRs, indicating that klotho gene delivery attenuated renal damage. Therefore, the suppressed klotho expression may play a role in the progression of spontaneous hypertension and renal damage in SHRs. AAV delivery of klotho may offer a new approach for the long-term control of hypertension and for renoprotection.
Cyclosporin A: antiparasite drug, modulator of the host-parasite relationship and immunosuppressant (1992)

Cyclosporin A (CsA), a cyclic undecapeptide with powerful properties of immunosuppression, acts on parasitic infections in laboratory animals in various ways. The outcome of drug administration in vivo varies with timing of treatment relative to infection, route of administration, dose and number of treatments applied. CsA is clearly antiparasitic against malaria, schistosomes, adult tapeworms, metacestodes and filarial nematodes. By contrast, it acts as an immunomodulator against trypanosomes and Giardia, by exacerbating infection; in the case of Leishmania spp. the drug acts variously. In some other infections CsA acts both as an antiparasite drug and as an immunosuppressant (Toxoplasma, avian coccidiosis and gastrointestinal nematodes). This range of activities is reviewed and possible modes of action discussed in the light of emerging data on in vitro drug activity and on putative receptor binding. The potential value of a non-immunosuppressive analogue of CsA in the control of parasitic infections of humans and domestic animals is considered but this paper lays particular stress on the seminal role of CsA as a laboratory tool.
Synthetic Amebicides. VIII. 7,7′‐[Iminobis(alkyleneimino) [bis[benz[c] acridines] and Congeneric 9‐Aminoacridines, 12‐Aminobenz[a] acridines, [2‐Aminobenz[b] acridines, and 4‐Aminoquinolines (1968)

Abstract Thirty‐five 7,7′‐(iminodialkylenediimino))bis[benz[ c ]acridines] (VII), 7,7′‐(alkylene‐ and phenylenediimino)bis[benz[ c ]acridines] (VIII and IXa‐c), [iminobis(alkyleneimino)]bis[acridines, benz[ a ]acridines, benz[ b ]acridines, and quinolines] (X, Xla‐c, XII, XIII, and XIVa‐c), and [alkylenebis(iminoalkyleneimino)]bis[acridines, benz[ c ]acridines, and quinolincs] (XVI, XVII, XVIIIa and b, and XIXa‐c) were synthesized by the condensation of one equivalent of the appropriate alkylenediamine with two equivalents of the requisite chloroheterocycle in phenol. Many of the bis(aminoheterocyclic) compounds are highly active against Entamoeba histolytica in vitro and in experimental animals.
Effects of transdermal testosterone gel on bone turnover markers and bone mineral density in hypogonadal men (2001)

Transdermal testosterone gel application for 6 months decreased bone resorption markers and increased osteoblastic activity markers for a short period, which resulted in a small but significant increase in BMD. Ongoing long-term studies should answer whether the observed increases in BMD are sustained or continue to be dependent on the dose of testosterone administered.
Isolation and Characterization of Chlorella Virus from Fresh Water in Korea and Application in Chlorella Transformation System (2005)

Chlorella viruses are large icosahedral, plaque-forming, dsDNA viruses that infect certain unicellular, chlorellalike green algae. The genomic DNA of over 300 kb contains many useful genes and promoters. Over 40 chlorella viruses have been isolated from fresh water in Korea since 1998. The viruses were amplified initially in chlorella strain NC64A, and pure isolates were obtained by repeated plaque isolation. SDS-PAGE analysis revealed similar but distinct protein patterns, both among the group of purified viruses and in comparison with the prototype chlorella virus PBCV-1. Digestions of the 330- to 350-kb genomic DNAs with 10 restriction enzymes revealed different restriction fragment patterns among the isolates. The tRNA-coding regions of 8 chlorella viruses were cloned and sequenced. These viruses contain 14-16 tRNA genes within a 1.2- to 2-kb region, except for the SS-1 isolate, which has a 1039-bp spacer in a cluster of 11 tRNA genes. Promoter regions of several early genes were isolated and their activities were analyzed in transformed chlorella. Some promoters showed stronger activity than commonly used CaMV 35S promoter and chlorella transformation vectors for heterologous protein are beings constructed using these promoters.
Lactic acid as a platform chemical in the biobased economy: the role of chemocatalysis (2013)

Upcoming bio-refineries will be at the heart of the manufacture of future transportation fuels, chemicals and materials. A narrow number of platform molecules are envisioned to bridge nature's abundant polysaccharide feedstock to the production of added-value chemicals and intermediate building blocks. Such platform molecules are well-chosen to lie at the base of a large product assortment, while their formation should be straightforward from the refined biomass, practical and energy efficient, without unnecessary loss of carbon atoms. Lactic acid has been identified as one such high potential platform. Despite its established fermentation route, sustainability issues – like gypsum waste and cost factors due to multi-step purification and separation requirements – will arise as soon as the necessary orders of magnitude larger volumes are needed. Innovative production routes to lactic acid and its esters are therefore under development, converting sugars and glycerol in the presence of chemocatalysts. Moreover, catalysis is one of the fundamental routes to convert lactic acid into a range of useful chemicals in a platform approach. This contribution attempts a critical overview of all advances in the field of homogeneous and heterogeneous catalysis and recognises a great potential of some of these chemocatalytic approaches to produce and transform lactic acid as well as some other promising α-hydroxy acids.
Inhibition of ErbB3 by a monoclonal antibody that locks the extracellular domain in an inactive configuration (2015)

ErbB3 (HER3) is a member of the EGF receptor (EGFR) family of receptor tyrosine kinases, which, unlike the other three family members, contains a pseudo kinase in place of a tyrosine kinase domain. In cancer, ErbB3 activation is driven by a ligand-dependent mechanism through the formation of heterodimers with EGFR, ErbB2, or ErbB4 or via a ligand-independent process through heterodimerization with ErbB2 overexpressed in breast tumors or other cancers. Here we describe the crystal structure of the Fab fragment of an antagonistic monoclonal antibody KTN3379, currently in clinical development in human cancer patients, in complex with the ErbB3 extracellular domain. The structure reveals a unique allosteric mechanism for inhibition of ligand-dependent or ligand-independent ErbB3-driven cancers by binding to an epitope that locks ErbB3 in an inactive conformation. Given the similarities in the mechanism of ErbB receptor family activation, these findings could facilitate structure-based design of antibodies that inhibit EGFR and ErbB4 by an allosteric mechanism.
Gold nanoparticle ensembles as heaters and actuators: melting and collective plasmon resonances (2006)

Abstract We describe the peculiar conditions under which optically driven gold nanoparticles (NPs) can significantly increase temperature or even melt a surrounding matrix. The heating and melting processes occur under light illumination and involve the plasmon resonance. For the matrix, we consider water, ice, and polymer. Melting and heating the matrix becomes possible if a nanoparticle size is large enough. Significant enhancement of the heating effect can appear in ensembles of NPs due to an increase of a volume of metal and electric-field amplification.
Excitation of surface waves (1958)

It is shown how to locate a dipole source above a dielectric surface so as either to produce as pure a surface wave as possible or to maximize the amount of energy carried by the surface wave.
Global and targeted gene expression and protein content in skeletal muscle of young men following short-term creatine monohydrate supplementation (2007)

Creatine monohydrate (CrM) supplementation has been shown to increase fat-free mass and muscle power output possibly via cell swelling. Little is known about the cellular response to CrM. We investigated the effect of short-term CrM supplementation on global and targeted mRNA expression and protein content in human skeletal muscle. In a randomized, placebo-controlled, crossover, double-blind design, 12 young, healthy, nonobese men were supplemented with either a placebo (PL) or CrM (loading phase, 20 g/day x 3 days; maintenance phase, 5 g/day x 7 days) for 10 days. Following a 28-day washout period, subjects were put on the alternate supplementation for 10 days. Muscle biopsies of the vastus lateralis were obtained and were assessed for mRNA expression (cDNA microarrays + real-time PCR) and protein content (Kinetworks KPKS 1.0 Protein Kinase screen). CrM supplementation significantly increased fat-free mass, total body water, and body weight of the participants (P < 0.05). Also, CrM supplementation significantly upregulated (1.3- to 5.0-fold) the mRNA content of genes and protein content of kinases involved in osmosensing and signal transduction, cytoskeleton remodeling, protein and glycogen synthesis regulation, satellite cell proliferation and differentiation, DNA replication and repair, RNA transcription control, and cell survival. We are the first to report this large-scale gene expression in the skeletal muscle with short-term CrM supplementation, a response that suggests changes in cellular osmolarity.
β2‐Adrenergic receptor regulates Toll‐like receptor‐4‐induced nuclear factor‐κB activation through β‐arrestin 2 (2008)

Toll-like receptors (TLRs) play an important role in innate immunity while, beta(2)-adrenergic receptors (beta(2)AR) provide the key linkages for the sympathetic nervous system to regulate the immune system. However, their role in macrophages remains uncertain. Here, we demonstrate the cross-talk between beta(2)AR and TLR signalling pathways. Expression of beta(2)AR was down-regulated by TLR4 ligand lipopolysaccharide (LPS) stimulation. To investigate the physiological consequence of this down-regulation RAW264 cells, a macrophage cell line, were transfected with a beta(2)AR expression vector (RAWar). Both LPS-stimulated inducible nitric oxide synthase (NOS II) expression and NO production were markedly suppressed in the RAWar cells. The activation of nuclear factor-kappaB (NF-kappaB) and degradation of the inhibitor of NF-kappaB (IkappaBalpha) in response to LPS were markedly decreased in these cells. The level of beta-arrestin 2, which regulates beta(2)AR signalling, was also reduced in RAW264 cells after stimulation with LPS, but not in RAWar cells. Overexpression of beta-arrestin 2 (RAWarr2) also inhibited NO production and NOS II expression. Furthermore, we demonstrated that beta-arrestin 2 interacted with cytosolic IkappaBalpha and that the level of IkappaBalpha coimmunoprecipitated by anti-beta-arrestin 2 antibodies was decreased in the RAW264 cells but not in RAWar or RAWarr2 cells. These findings suggest that LPS-stimulated signals suppress beta(2)AR expression, leading to down-regulation of beta-arrestin 2 expression, which stabilizes cytosolic IkappaBalpha and inhibits the NF-kappaB activation essential for NOS II expression, probably to ensure rapid and sufficient production of NO in response to microbial attack.
Time Course of Lung Changes at Chest CT during Recovery from Coronavirus Disease 2019 (COVID-19) (2020)

Background Chest CT is used to assess the severity of lung involvement in coronavirus disease 2019 (COVID-19). Purpose To determine the changes in chest CT findings associated with COVID-19 from initial diagnosis until patient recovery. Materials and Methods This retrospective review included patients with real-time polymerase chain reaction-confirmed COVID-19 who presented between January 12, 2020, and February 6, 2020. Patients with severe respiratory distress and/or oxygen requirement at any time during the disease course were excluded. Repeat chest CT was performed at approximately 4-day intervals. Each of the five lung lobes was visually scored on a scale of 0 to 5, with 0 indicating no involvement and 5 indicating more than 75% involvement. The total CT score was determined as the sum of lung involvement, ranging from 0 (no involvement) to 25 (maximum involvement). Results Twenty-one patients (six men and 15 women aged 25-63 years) with confirmed COVID-19 were evaluated. A total of 82 chest CT scans were obtained in these patients, with a mean interval (±standard deviation) of 4 days ± 1 (range, 1-8 days). All patients were discharged after a mean hospitalization period of 17 days ± 4 (range, 11-26 days). Maximum lung involved peaked at approximately 10 days (with a calculated total CT score of 6) from the onset of initial symptoms (<i>R</i><sup>2</sup> = 0.25, <i>P</i> < .001). Based on quartiles of chest CT scans from day 0 to day 26 involvement, four stages of lung CT findings were defined. CT scans obtained in stage 1 (0-4 days) showed ground-glass opacities (18 of 24 scans [75%]), with a mean total CT score of 2 ± 2; scans obtained in stage 2 (5-8 days) showed an increase in both the crazy-paving pattern (nine of 17 scans [53%]) and total CT score (mean, 6 ± 4; <i>P</i> = .002); scans obtained in stage 3 (9-13 days) showed consolidation (19 of 21 scans [91%]) and a peak in the total CT score (mean, 7 ± 4); and scans obtained in stage 4 (≥14 days) showed gradual resolution of consolidation (15 of 20 scans [75%]) and a decrease in the total CT score (mean, 6 ± 4) without crazy-paving pattern. Conclusion In patients recovering from coronavirus disease 2019 (without severe respiratory distress during the disease course), lung abnormalities on chest CT scans showed greatest severity approximately 10 days after initial onset of symptoms. © RSNA, 2020.