gebhart/patrepeval huggingface dataset:
Multilayer DNA Origami Packed on a Square Lattice (2009)

Molecular self-assembly using DNA as a structural building block has proven to be an efficient route to the construction of nanoscale objects and arrays of increasing complexity. Using the remarkable "scaffolded DNA origami" strategy, Rothemund demonstrated that a long single-stranded DNA from a viral genome (M13) can be folded into a variety of custom two-dimensional (2D) shapes using hundreds of short synthetic DNA molecules as staple strands. More recently, we generalized a strategy to build custom-shaped, three-dimensional (3D) objects formed as pleated layers of helices constrained to a honeycomb lattice, with precisely controlled dimensions ranging from 10 to 100 nm. Here we describe a more compact design for 3D origami, with layers of helices packed on a square lattice, that can be folded successfully into structures of designed dimensions in a one-step annealing process, despite the increased density of DNA helices. A square lattice provides a more natural framework for designing rectangular structures, the option for a more densely packed architecture, and the ability to create surfaces that are more flat than is possible with the honeycomb lattice. Thus enabling the design and construction of custom 3D shapes from helices packed on a square lattice provides a general foundational advance for increasing the versatility and scope of DNA nanotechnology.
Cleavage of p220 by Purified Poliovirus 2Apro in Cell-Free Systems:  Effects on Translation of Capped and Uncapped mRNAs (1997)

Poliovirus protease 2A(pro) has been obtained in soluble form as a fusion protein with maltose binding protein (MBP). Addition of MBP-2A(pro) to rabbit reticulocyte cell-free systems gives rise to efficient cleavage of the initiation factor of translation p220 (eIF-4G). Translation of capped mRNA encoding the influenza virus NP protein is severely impaired in lysates in which p220 has been proteolytically cleaved. This inhibition is dependent on the concentration of mRNA added to the lysate. Thus, increasing the concentrations of mRNA substantially overcomes the blockade of NP synthesis after p220 cleavage. Notably, translation of uncapped NP mRNA is also compromised in p220-deficient rabbit reticulocyte lysates, suggesting that p220 participates in the translation of both capped and uncapped NP mRNAs. The effects of p220 proteolysis by poliovirus 2A(pro) have also been assayed on luciferase mRNA translation. Three types of mRNAs encoding for luciferase have been examined: capped, uncapped, and mRNA bearing the poliovirus 5' leader region (leader luc mRNA). Synthesis of luciferase directed by any of these mRNAs was inhibited after cleavage of p220 in rabbit reticulocyte lysates. Interestingly, supplementation of the lysate with HeLa cell extracts stimulates leader luc mRNA translation by poliovirus 2A(pro). These results indicate that activation of translation of mRNAs bearing the poliovirus leader region promoted by this poliovirus protease requires a factor present in HeLa cell extracts. These findings agree well with recent experiments implicating p220 not only in protein synthesis directed by capped mRNAs but also in the translation of naturally uncapped mRNAs.
Lycium Barbarum Polysaccharides Reduce Neuronal Damage, Blood-Retinal Barrier Disruption and Oxidative Stress in Retinal Ischemia/Reperfusion Injury (2011)

Neuronal cell death, glial cell activation, retinal swelling and oxidative injury are complications in retinal ischemia/reperfusion (I/R) injuries. Lycium barbarum polysaccharides (LBP), extracts from the wolfberries, are good for "eye health" according to Chinese medicine. The aim of our present study is to explore the use of LBP in retinal I/R injury. Retinal I/R injury was induced by surgical occlusion of the internal carotid artery. Prior to induction of ischemia, mice were treated orally with either vehicle (PBS) or LBP (1 mg/kg) once a day for 1 week. Paraffin-embedded retinal sections were prepared. Viable cells were counted; apoptosis was assessed using TUNEL assay. Expression levels of glial fibrillary acidic protein (GFAP), aquaporin-4 (AQP4), poly(ADP-ribose) (PAR) and nitrotyrosine (NT) were investigated by immunohistochemistry. The integrity of blood-retinal barrier (BRB) was examined by IgG extravasations. Apoptosis and decreased viable cell count were found in the ganglion cell layer (GCL) and the inner nuclear layer (INL) of the vehicle-treated I/R retina. Additionally, increased retinal thickness, GFAP activation, AQP4 up-regulation, IgG extravasations and PAR expression levels were observed in the vehicle-treated I/R retina. Many of these changes were diminished or abolished in the LBP-treated I/R retina. Pre-treatment with LBP for 1 week effectively protected the retina from neuronal death, apoptosis, glial cell activation, aquaporin water channel up-regulation, disruption of BRB and oxidative stress. The present study suggests that LBP may have a neuroprotective role to play in ocular diseases for which I/R is a feature.
Plasmapheresis Eliminates the Negative Impact of AAV Antibodies on Microdystrophin Gene Expression Following Vascular Delivery (2013)

Duchenne muscular dystrophy is a monogenic disease potentially treatable by gene replacement. Use of recombinant adeno-associated virus (AAV) will ultimately require a vascular approach to broadly transduce muscle cells. We tested the impact of preexisting AAV antibodies on microdystrophin expression following vascular delivery to nonhuman primates. Rhesus macaques were treated by isolated limb perfusion using a fluoroscopically guided catheter. In addition to serostatus stratification, the animals were placed into one of the three immune suppression groups: no immune suppression, prednisone, and triple immune suppression (prednisone, tacrolimus, and mycophenolate mofetil). The animals were analyzed for transgene expression at 3 or 6 months. Microdystrophin expression was visualized in AAV, rhesus serotype 74 sero-negative animals (mean: 48.0 ± 20.8%) that was attenuated in sero-positive animals (19.6 ± 18.7%). Immunosuppression did not affect transgene expression. Importantly, removal of AAV binding antibodies by plasmapheresis in AAV sero-positive animals resulted in high-level transduction (60.8 ± 18.0%), which is comparable with that of AAV sero-negative animals (53.7 ± 7.6%), whereas non-pheresed sero-positive animals demonstrated significantly lower transduction levels (10.1 ± 6.0%). These data support the hypothesis that removal of AAV binding antibodies by plasmapheresis permits successful and sustained gene transfer in the presence of preexisting immunity (natural infection) to AAV.
Blue Light Eliminates Community-Acquired Methicillin-Resistant Staphylococcus aureus in Infected Mouse Skin Abrasions (2013)

There exists a therapeutic window of blue light for bacterial infections where bacteria are selectively inactivated by blue light while host tissue cells are preserved. Blue light therapy has the potential to rapidly reduce the bacterial load in SSTI.
Electronic Measurements of Single-Molecule Processing by DNA Polymerase I (Klenow Fragment) (2013)

Bioconjugating single molecules of the Klenow fragment of DNA polymerase I into electronic nanocircuits allowed electrical recordings of enzymatic function and dynamic variability with the resolution of individual nucleotide incorporation events. Continuous recordings of DNA polymerase processing multiple homopolymeric DNA templates extended over 600 s and through >10,000 bond-forming events. An enzymatic processivity of 42 nucleotides for a template of the same length was directly observed. Statistical analysis determined key kinetic parameters for the enzyme's open and closed conformations. Consistent with these nanocircuit-based observations, the enzyme's closed complex forms a phosphodiester bond in a highly efficient process >99.8% of the time, with a mean duration of only 0.3 ms for all four dNTPs. The rate-limiting step for catalysis occurs during the enzyme's open state, but with a nearly 2-fold longer duration for dATP or dTTP incorporation than for dCTP or dGTP into complementary, homopolymeric DNA templates. Taken together, the results provide a wealth of new information complementing prior work on the mechanism and dynamics of DNA polymerase I.
A realistic simulation framework to evaluate ionospheric tomography (2019)

Observation of the 3-dimensional (3-D) electron density of the ionosphere is useful to study large-scale physical processes in space weather events. Ionospheric data assimilation and ionospheric tomography are methods that can create an image of the 3-D electron density distribution. While multiple techniques have been developed over the past 30 years, there are relatively few studies that show the accuracy of the algorithms. This paper outlines a novel simulation approach to test the quality of an ionospheric tomographic inversion. The approach uses observations from incoherent scatter radar (ISR) scans and extrapolates them spatially to create a realistic ionospheric representation. A set of total electron content (TEC) measurements can then be simulated using real geometries from satellites and ground receivers. This data set, for which the ‘truth’ ionosphere is known, is used as input for a tomographic inversion algorithm to estimate the spatial distribution of electron density. The reconstructed ionospheric maps are compared with the truth ionosphere to calculate the difference between the images and the truth. To demonstrate the effectiveness of this simulation framework, an inversion algorithm called MIDAS (Multi-Instrument Data Analysis Software) is evaluated for three geographic regions with differing receiver networks. The results show the importance of the distribution and density of GPS receivers and the use of a realistic prior conditioning of the vertical electron density profile. This paper demonstrates that when these requirements are met, MIDAS can reliably estimate the ionospheric electron density. When the region under study is well covered by GPS receivers, as in mainland Europe or North America, the errors in vertical total electron content (vTEC) are smaller than 1 TECu (2–4%) . In regions with fewer and more sparsely distributed receivers, the errors can be as high as 20–40%. This is caused by poor data coverage and poor spatial resolution of the reconstruction, which has an important effect on the calibration process of the algorithm.
Analysis of differential gene expression by display of 3' end restriction fragments of cDNAs. (1996)

We have developed an approach to study changes in gene expression by selective PCR amplification and display of 3' end restriction fragments of double-stranded cDNAs. This method produces highly consistent and reproducible patterns, can detect almost all mRNAs in a sample, and can resolve hidden differences such as bands that differ in their sequence but comigrate on a gel. Bands corresponding to known cDNAs move to predictable positions on the gel, making this a powerful approach to correlate gel patterns with cDNA data bases. Applying this method, we have examined differences in gene expression patterns during T-cell activation. Of a total of 700 bands that were evaluated in this study, as many as 3-4% represented mRNAs that are upregulated, while approximately 2% were down-regulated within 4 hr of activation of Jurkat T cells. These and other results suggest that this approach is suitable for the systematic, expeditious, and nearly exhaustive elucidation of subtle changes in the patterns of gene expression in cells with altered physiologic states.
Information capacity and power control in single-cell multiuser communications (2002)

We consider a power control scheme for maximizing the information capacity of the uplink in single-cell multiuser communications with frequency-flat fading, under the assumption that the users attenuations are measured perfectly. Its main characteristics are that only one user transmits over the entire bandwidth at any particular time instant and that the users are allocated more power when their channels are good, and less when they are bad. Moreover, these features are independent of the statistics of the fading. Numerical results are presented for the case of single-path Rayleigh fading. We show that an increase in capacity over a perfectly-power controlled (Gaussian) channel can be achieved, especially if the number of users is large. By examining the bit error-rate with antipodal signalling, we show the inherent diversity in multiuser communications over fading channels.
Critical Involvement of OX40 Ligand Signals in the T Cell Priming Events During Experimental Autoimmune Encephalomyelitis (2001)

OX40 ligand (OX40L) expressed on APCs, and its receptor, OX40 present on activated T cells, are members of the TNF/TNFR family, respectively, and have been located at the sites of inflammatory conditions. We have observed in OX40L-deficient mice (OX40L(-/-)) an impaired APC capacity and in our recently constructed transgenic mice expressing OX40L (OX40L-Tg), a markedly enhanced T cell response to protein Ags. Using these mice, we demonstrate here the critical involvement of the OX40L-OX40 interaction during the T cell priming events in the occurrence of experimental autoimmune encephalomyelitis (EAE). In OX40L(-/-) mice, abortive T cell priming greatly reduced the clinical manifestations of actively induced EAE, coupled with a reduction in IFN-gamma, IL-2, and IL-6 production in vitro. Adoptive transfer experiments however revealed an efficient transfer of disease to OX40L(-/-) mice using wild-type donor T cells, indicating an intact capacity of OX40L(-/-) mice to initiate effector responses. On the other hand, OX40L(-/-) donor T cells failed to transfer disease to wild-type recipient mice. Furthermore, OX40L-Tg mice developed a greater severity of EAE despite a delayed onset, while both OX40L-Tg/CD28(-/-) and OX40L-Tg/CD40(-/-) mice failed to develop EAE demonstrating a requisite for these molecules. These findings indicate a pivotal role played by OX40L in the pathogenesis of EAE.
Reexamination of the mechanism of hydroxyl radical adducts formed from the reaction between familial amyotrophic lateral sclerosis-associated Cu,Zn superoxide dismutase mutants and H 2 O 2 (1998)

Amyotrophic lateral sclerosis (ALS) involves the progressive degeneration of motor neurons in the spinal cord and motor cortex. Mutations to Cu,Zn superoxide dismutase (SOD) linked with familial ALS are reported to increase hydroxyl radical adduct formation from hydrogen peroxide as measured by spin trapping with 5, 5'-dimethyl-1-pyrrolline N-oxide (DMPO). In the present study, we have used oxygen-17-enriched water and H2O2 to reinvestigate the mechanism of DMPO/.OH formation from the SOD and SOD mutants. The relative ratios of DMPO/.17OH and DMPO/.16OH formed in the Fenton reaction were 90% and 10%, respectively, reflecting the ratios of H217O2 to H216O2. The reaction of the WT SOD with H217O2 in bicarbonate/CO2 buffer yielded 63% DMPO/.17OH and 37% DMPO/.16OH. Similar results were obtained from the reaction between familial ALS SOD mutants and H217O2: DMPO/.17OH (64%); DMPO/.16OH (36%) from A4V and DMPO/.17OH (62%); and DMPO/.16OH (38%) from G93A. These results were confirmed further by using 5-diethoxyphosphoryl-5-methyl-1-pyrroline N-oxide spin trap, a phosphorylated analog of DMPO. Contrary to earlier reports, the present results indicate that a significant fraction of DMPO/.OH formed during the reaction of SOD and familial ALS SOD mutants with H2O2 is derived from the incorporation of oxygen from water due to oxidation of DMPO to DMPO/.OH presumably via DMPO radical cation. No differences were detected between WT and mutant SODs, neither in the concentration of DMPO/.OH or DEPMPO/.OH formed nor in the relative incorporation of oxygen from H2O2 or water.
Suppression of Philadelphia1 leukemia cell growth in mice by BCR-ABL antisense oligodeoxynucleotide. (1994)

When injected into SCID mice, the Philadelphia chromosome-positive chronic myeloid leukemia-blast crisis cell line BV173 induces a disease process closely resembling that seen in leukemia patients. At 1 and 3 weeks after injection of 10(6) BV173 cells, CD10+ cells were detected in the bone marrow of the mice, leukemic colonies grew from bone marrow and spleen cell suspensions, and BCR-ABL transcripts were detectable in bone marrow, spleen, peripheral blood, liver, and lungs. Systemic treatment of the leukemic mice with a 26-mer BCR-ABL antisense oligodeoxynucleotide (1 mg/day for 9 days) induced disappearance of CD10+ and clonogenic leukemic cells and a marked decrease in BCR-ABL mRNA in mouse tissues. Untreated mice or mice treated with a BCR-ABL sense oligodeoxynucleotide or a 6-base-mismatched antisense oligodeoxynucleotide oligodeoxynucleotide were dead 8-13 weeks after leukemia cell injection; in marked contrast, mice treated with BCR-ABL antisense oligodeoxynucleotide died of leukemia 18-23 weeks after injection of leukemic cells. These findings provide evidence for the in vivo effectiveness of an anticancer therapy based on antisense oligodeoxynucleotides targeting a tumor-specific gene.
The eICU: It’s not just telemedicine (2001)

Intensive care units (ICUs) are major sites for medical errors and adverse events. Suboptimal outcomes reflect a widespread failure to implement care delivery systems that successfully address the complexity of modern ICUs. Whereas other industries have used information technologies to fundamentally improve operating efficiency and enhance safety, medicine has been slow to implement such strategies. Most ICUs do not even track performance; fewer still have the capability to examine clinical data and use this information to guide quality improvement initiatives. This article describes a technology-enabled care model (electronic ICU, or eICU) that represents a new paradigm for delivery of critical care services. A major component of the model is the use of telemedicine to leverage clinical expertise and facilitate a round-the-clock proactive care by intensivist-led teams of ICU caregivers. Novel data presentation formats, computerized decision support, and smart alarms are used to enhance efficiency, increase effectiveness, and standardize clinical and operating processes. In addition, the technology infrastructure facilitates performance improvement by providing an automated means to measure outcomes, track performance, and monitor resource utilization. The program is designed to support the multidisciplinary intensivist-led team model and incorporates comprehensive ICU re-engineering efforts to change practice behavior. Although this model can transform ICUs into centers of excellence, success will hinge on hospitals accepting the underlying value proposition and physicians being willing to change established practices.
Ruxolitinib: A New JAK1/2 Inhibitor That Offers Promising Options for Treatment of Myelofibrosis (2011)

Ruxolitinib (INCB018424) is the first potent, selective, oral inhibitor of JAK1 and 2 being developed for clinical use. Its major cellular and systemic effects are proliferation inhibition, apoptosis induction and reduction in cytokine plasma levels, all mediated by the drug's inhibition of JAKs' ability to phosphorylate STAT. In initial clinical trials of its use in myelofibrosis, ruxolitinib exhibited durable efficacy in reduction of splenomegaly and alleviation of constitutional symptoms. Patients also showed weight gain and improvement in general physical condition. The dose-limiting toxicity was thrombocytopenia. In preliminary findings of a Phase III trial in patients with primary, postpolycythemia-vera, or postessential-thrombocythemia myelofibrosis, administration at an initial dosage of 15 or 20 mg twice daily led to a spleen-volume response rate (≥ 35% reduction at 24 weeks) of 41.9 versus 0.7% for placebo (p < 0.0001); furthermore, 45.9% of the ruxolitinib recipients had ≥ 50% improvement in symptom score (on the modified Myelofibrosis Symptom Assessment Form version 2.0) versus 5.3% for placebo (p < 0.0001). Ruxolitinib recipients also showed improvement in parameters of quality of life.
Pseudoprogression of Glioblastoma after Chemo- and Radiation Therapy: Diagnosis by Using Dynamic Susceptibility-weighted Contrast-enhanced Perfusion MR Imaging with Ferumoxytol versus Gadoteridol and Correlation with Survival (2012)

Ferumoxytol as a blood pool agent facilitates differentiation between tumor progression and pseudoprogression, appears to be a good prognostic biomarker, and unlike gadoteridol, does not require contrast agent leakage correction.
Abnormal Proteins Serve as Eukaryotic Stress Signals and Trigger the Activation of Heat Shock Genes (1986)

Heat shock protein (hsp) genes, a group of ubiquitous genes, are activated by various metabolic stresses. The suggestion that denaturation of intracellular proteins may be produced by the metabolic stresses and then signal the activation of the hsp genes was examined by co-injection of purified proteins and hsp genes into frog oocytes. Activation of hsp genes was observed if the proteins were denatured prior to injection but not if they were introduced in their native form. Furthermore, the activation of hsp genes by abnormal proteins and by heat shock appears to occur by a common mechanism. A model for the transcriptional regulation of the genes is based on competition for degradation between abnormal intracellular proteins and a labile regulatory factor.
A 0.13-$\mu{\hbox {m}}$ 1-GS/s CMOS Discrete-Time FFT Processor for Ultra-Wideband OFDM Wireless Receivers (2011)

A discrete-time (DT) fast Fourier transform (FFT) processor is presented as an architectural approach to Fourier transform processing multigigahertz of spectral bandwidth. The processor is considered with the specific application of demodulating orthogonal frequency-division multiplexing (OFDM) modulation. The processor enables increased receiver linearity beyond that which is typically limited by the signal-to-noise-and-distortion ratio of high sample rate ADCs by performing OFDM demodulation in the DT domain. The circuit design of the prototype DT-FFT processor is presented and measurement results from the CMOS 0.13-μm test chip are shown. Results show that the processor demodulates OFDM at 1 GS/s with an accuracy better than 2.8% error vector magnitude while drawing 25 mW from a 1.2-V power supply. The processor demonstrates a measured dynamic range of 49 dB, a 13-dB improvement over that of a 6-bit quantization limited all-digital FFT processor and ADC pair. The DT-FFT is also shown to better tolerate large blocking signals with an 8-dB dynamic range improvement. The DT-FFT core area is 450 μm × 450 μm.
Urinary Metabolomics on the Biochemical Profiles in Diet-Induced Hyperlipidemia Rat Using Ultraperformance Liquid Chromatography Coupled with Quadrupole Time-of-Flight SYNAPT High-Definition Mass Spectrometry (2014)

Ultraperformance liquid chromatography coupled with quadrupole time-of-flight synapt high-definition mass spectrometry metabolomics was used to characterize the urinary metabolic profiling of diet-induced hyperlipidaemia in a rat model. Analysis was done by orthogonal partial least squares discriminant analysis, correlation analysis, heat map analysis, and KEGG pathways analysis. Potential biomarkers were chosen by S-plot and were identified by accurate mass, isotopic pattern, and MS/MS fragments information. Significant differences in fatty acid, amino acid, nucleoside, and bile acid were observed, indicating the perturbations of fatty acid, amino acid, nucleoside, and bile acid metabolisms in diet-induced hyperlipidaemia rats. This study provides further insight into the metabolic profiling across a wide range of biochemical pathways in response to diet-induced hyperlipidaemia.