gebhart/patrepeval huggingface dataset:
In vitro evolution of a neutralizing human antibody to human immunodeficiency virus type 1 to enhance affinity and broaden strain cross-reactivity. (1994)

A method is described that allows for the improvement of antibody affinity. This method, termed complementary-determining region (CDR) walking, does not require structural information on either antibody or antigen. Complementary-determining regions are targeted for random mutagenesis followed by selection for fitness, in this case increased binding affinity, by the phage-display approach. The current study targets a human CD4-binding-site anti-gp120 antibody that is potently and broadly neutralizing. Evolution of affinity of this antibody demonstrates in this case that affinity can be increased while reactivity to variants of human immunodeficiency virus type 1 is broadened. The neutralizing ability of this antibody is improved, as assayed with laboratory and primary clinical isolates of human immunodeficiency virus type 1. The ability to produce human antibodies of exceptional affinity and broad neutralizing ability has implications for the therapeutic and prophylactic application of antibodies for human immunodeficiency virus type 1 infection.
Hartwig–Buchwald Amination on Solid Supports: a Novel Access to a Diverse Set of 1H-Benzotriazoles (2007)

Hartwig-Buchwald amination reactions of bromo- and chloroarenes were performed on solid supports with triazene-linked arenes. Immobilized 2-haloarenes were treated with diverse primary amines and anilines at 100 degrees C under palladium catalysis to yield N-substituted 2-aminoarenes. The latter were alternatively formed through reaction of bromo- and chloroarenes with immobilized primary 2-aminobenzenes. Subsequent acidic cleavage furnished 1H-benzotriazoles in high purities. The two described routes allow a broad range of the substitution pattern of N-substituted 1H-benzotriazoles.
Adenovirus-mediated gene delivery into mouse spermatogonial stem cells (2007)

Spermatogonial stem cells represent a self-renewing population of spermatogonia, and continuous division of these cells supports spermatogenesis throughout the life of adult male animals. Previous attempts to introduce adenovirus vectors into spermatogenic cells, including spermatogonial stem cells, have failed to yield evidence of infection, suggesting that male germ cells may be resistant to adenovirus infection. In this study we show the feasibility of transducing spermatogonial stem cells by adenovirus vectors. When testis cells from ROSA26 Cre reporter mice were incubated in vitro with a Cre-expressing adenovirus vector, Cre-mediated recombination occurred at an efficiency of 49-76%, and the infected spermatogonial stem cells could reinitiate spermatogenesis after transplantation into seminiferous tubules of infertile recipient testes. No evidence of germ-line integration of adenovirus vector could be found in offspring from infected stem cells that underwent Cre-mediated recombination, which suggests that the adenovirus vector infected the cells but did not stably integrate into the germ line. Nevertheless, these results suggest that adenovirus may inadvertently integrate into the patient's germ line and indicate that there is no barrier to adenovirus infection in spermatogonial stem cells.
Learning Systems for Electric Consumption of Buildings (2009)

Individual appliances' electricity consumption is automatically disaggregated from a single custom metering system on the main feed to an occupied residential building. A data acquisition system samples voltage and current at 100 kHz, then calculates real and reactive power, harmonics, and other features at 20Hz. A probabilistic eventdetector using the generalized likelihood ratio (GLR) matches human-labeled events to the time-series of features. Machine-learning classification was most successful with the 1-nearest-neighbor algorithm, correctly identifying 90% of the laboratory-generated training events and 79% of validation examples. The challenge of obtaining adequate training data for the real-world home leads to the development of the Wire Spy, a wirelessly-networked event detector with an inductive sensor which clamps to the cable of an appliance.
[Quantitative myocardial perfusion assessment with magnetic resonance imaging in patients with coronary artery disease]. (2004)

Absolute MBF and MBFR calculation by first-pass contrast perfusion MRI are feasible in patients with CAD before and after revascularization.
Whole-Genome Characterization of Human and Simian Immunodeficiency Virus Intrahost Diversity by Ultradeep Pyrosequencing (2010)

Rapid evolution and high intrahost sequence diversity are hallmarks of human and simian immunodeficiency virus (HIV/SIV) infection. Minor viral variants have important implications for drug resistance, receptor tropism, and immune evasion. Here, we used ultradeep pyrosequencing to sequence complete HIV/SIV genomes, detecting variants present at a frequency as low as 1%. This approach provides a more complete characterization of the viral population than is possible with conventional methods, revealing low-level drug resistance and detecting previously hidden changes in the viral population. While this work applies pyrosequencing to immunodeficiency viruses, this approach could be applied to virtually any viral pathogen.
Photocleavable biotin phosphoramidite for 5'-end-labeling, affinity purification and phosphorylation of synthetic oligonucleotides (1996)

We report the design, synthesis and evaluation of a non-nucleosidic photocleavable biotin phosphoramidite (PCB-phosphoramidite) which provides a simple method for purification and phosphorylation of oligonucleotides. This reagent introduces a photocleavable biotin label (PCB) on the 5'-terminal phosphate of synthetic oligonucleotides and is fully compatible with automated solid support synthesis. HPLC analysis shows that the PCB moiety is introduced predominantly on full-length sequences and is retained during cleavage of the synthetic oligonucleotide from the solid support and during subsequent deprotection with ammonia. The full-length 5-PCB-labeled oligonucleotide can then be selectively isolated from the crude oligonucleotide mixture by incubation with immobilized streptavidin. Upon irradiation with 300-350 nm light the 5'-PCB moiety is cleaved with high efficiency in <4 min, resulting in rapid release of affinity-purified 5'-phosphorylated oligonucleotides into solution. 5'-PCB-labeled oligonucleotides should be useful in a variety of applications in molecular biology, including cassette mutagenesis and PCR. As an example, PCB-phosphoramidite has been used for the synthesis, purification and phosphorylation of 50-and 60mer oligonucleotides.
Beyond the Treatment of Epilepsy: New Applications of Vagus Nerve Stimulation in Psychiatry (2003)

Vagus nerve stimulation (VNS) in humans generally refers to stimulation of the left vagus nerve at the cervical level VNS is an established treatment largely devoid of severe side effect for medically refractory partial onset seizures and has been used in more than 16,000 patients. Over the past 5 years, applications in other neuropsychiatric disorders have been investigated with a special emphasis on depression. Recent data from an open-label, multi-center pilot study involving 60 patients suggest a potential clinical usefulness in the acute and maintenance treatment of drug-resistant depressive disorder. The perspective of VNS as along-term treatment with the advantage of assured compliance makes it an interesting technique to potentially treat drug-resistant depression. However, definite therapeutic effects of clinical significance remain to be confirmed in large placebo-controlled trial. Results of clinical pilot studies involving patients suffering from obesity and Alzheimer's disease indicate that VNS might induce weight loss and improve cognition. Besides its clinical usefulness, VNS can be used as a research tool, allowing neurophysiologic investigations of the parasympathetic system and its interactions with other parts of the central nervous system.
Chemical Nanosensors Based on Composite Molecularly Imprinted Polymer Particles and Surface‐Enhanced Raman Scattering (2010)

Chemical nanosensors with a submicrometer core–shell composite design, based on a polymer core, a molecularly imprinted polymer (MIP) shell for specific analyte recognition, and an interlayer of gold nanoparticles for signal amplification, are described. SERS measurements on single nanosensors yield detection limits of 10−7 M for the β-blocker propranolol, several orders of magnitude lower than on plain MIP spheres. Detailed facts of importance to specialist readers are published as ”Supporting Information”. Such documents are peer-reviewed, but not copy-edited or typeset. They are made available as submitted by the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Reducing the Effects of PCR Amplification and Sequencing Artifacts on 16S rRNA-Based Studies (2011)

The advent of next generation sequencing has coincided with a growth in interest in using these approaches to better understand the role of the structure and function of the microbial communities in human, animal, and environmental health. Yet, use of next generation sequencing to perform 16S rRNA gene sequence surveys has resulted in considerable controversy surrounding the effects of sequencing errors on downstream analyses. We analyzed 2.7×10(6) reads distributed among 90 identical mock community samples, which were collections of genomic DNA from 21 different species with known 16S rRNA gene sequences; we observed an average error rate of 0.0060. To improve this error rate, we evaluated numerous methods of identifying bad sequence reads, identifying regions within reads of poor quality, and correcting base calls and were able to reduce the overall error rate to 0.0002. Implementation of the PyroNoise algorithm provided the best combination of error rate, sequence length, and number of sequences. Perhaps more problematic than sequencing errors was the presence of chimeras generated during PCR. Because we knew the true sequences within the mock community and the chimeras they could form, we identified 8% of the raw sequence reads as chimeric. After quality filtering the raw sequences and using the Uchime chimera detection program, the overall chimera rate decreased to 1%. The chimeras that could not be detected were largely responsible for the identification of spurious operational taxonomic units (OTUs) and genus-level phylotypes. The number of spurious OTUs and phylotypes increased with sequencing effort indicating that comparison of communities should be made using an equal number of sequences. Finally, we applied our improved quality-filtering pipeline to several benchmarking studies and observed that even with our stringent data curation pipeline, biases in the data generation pipeline and batch effects were observed that could potentially confound the interpretation of microbial community data.
Overweight, Obesity, and Depression (2010)

This meta-analysis confirms a reciprocal link between depression and obesity. Obesity was found to increase the risk of depression, most pronounced among Americans and for clinically diagnosed depression. In addition, depression was found to be predictive of developing obesity.
An Endocytosed TGN38 Chimeric Protein Is Delivered to the TGN after Trafficking through the Endocytic Recycling Compartment in CHO Cells (1998)

To examine TGN38 trafficking from the cell surface to the TGN, CHO cells were stably transfected with a chimeric transmembrane protein, TacTGN38. We used fluorescent and 125I-labeled anti-Tac IgG and Fab fragments to follow TacTGN38's postendocytic trafficking. At steady-state, anti-Tac was mainly in the TGN, but shortly after endocytosis it was predominantly in early endosomes. 11% of cellular TacTGN38 is on the plasma membrane. Kinetic analysis of trafficking of antibodies bound to TacTGN38 showed that after short endocytic pulses, 80% of internalized anti-Tac returned to the cell surface (t1/2 = 9 min), and the remainder trafficked to the TGN. When longer filling pulses and chases were used to load anti-Tac into the TGN, it returned to the cell surface with a t1/2 of 46 min. Quantitative confocal microscopy analysis also showed that fluorescent anti-Tac fills the TGN with a 46-min t1/2. Using the measured rate constants in a simple kinetic model, we predict that 82% of TacTGN38 is in the TGN, and 7% is in endosomes. TacTGN38 leaves the TGN slowly, which accounts for its steady-state distribution despite the inefficient targeting from the cell surface to the TGN.
Apolipoprotein E ϵ4 Count Affects Age at Onset of Alzheimer Disease,but Not Lifetime Susceptibility (2004)

The APOE epsilon4 allele acts as a potent risk factor for AD by accelerating onset. However, the risk of AD appears heterogeneous in ways independent of APOE. Some individuals seem destined to escape AD, even over an extended lifespan. Their relative invulnerability may reflect other genes or environmental factors that can be investigated.
11 Protein Synthesis and Translational Control in Saccharomyces cerevisiae (1991)

I. INTRODUCTION The process of translation in Saccharomyces cerevisiae does not appear to differ fundamentally from the way it occurs in other organisms. Thus, much of what follows represents a comparison of the components and reactions of the protein synthetic machinery in yeast with their counterparts in other organisms, both prokaryotic and eukaryotic. For example, aminoacylation of tRNA and polypeptide chain elongation appear to be very similar in yeast and Escherichia coli, and, although the mechanism of translation initiation in Saccharomyces differs importantly from that described for bacteria, it closely resembles the process elucidated for plants and animals. Despite these similarities with other well-studied systems, the powerful genetic techniques developed for Saccharomyces make it very worthwhile to study protein synthesis in this organism. As described below, the genes encoding many components of the translational apparatus have been isolated from yeast and are being manipulated with genetic techniques to learn the complete functions of their gene products in vivo. This enterprise is particularly important for the reactions involved in translation initiation for which many differences exist between eukaryotes and prokaryotes. Mutational analysis of yeast should indicate whether the large number of proteins implicated in the process of initiation in eukaryotes from biochemical studies of in vitro systems is actually required for translation in vivo. This approach is extremely difficult for the multicellular organisms used most frequently to study eukaryotic protein synthesis. In addition, the isolation of mutations that alter the efficiency or fidelity of protein synthesis in yeast is likely to...
Highly infiltrative brain tumours show reduced chemosensitivity associated with a stem cell‐like phenotype (2009)

Aims: Cancer stem‐like cells might have important functions in chemoresistance. We have developed a model where highly infiltrative brain tumours with a stem‐like phenotype were established by orthotopic transplantation of human glioblastomas to immunodeficient rats. Serial passaging gradually transformed the tumours into a less invasive and more angiogenic phenotype (high‐generation tumours). The invasive phenotype (low‐generation tumours) was characterized by an increase in stem cell markers and increased phosphorylation of kinases in the phosphatidylinositol 3‐kinase (PI3K)/AKT pathway. These markers were reduced in the serially passaged vascular tumours. The present study was aimed at investigating how the two phenotypes responded in vitro to doxorubicin, a clinically potent cytotoxic drug for solid tumours. Methods: Biopsy spheroids were implanted and passaged intracranially in nude rats. Gene expression and protein analyses were performed, and drug sensitivity was assessed. Results: Microarray analysis revealed gene ontology categories connected to developmental aspects and negative regulators of differentiation, especially in the infiltrative stem cell‐like tumours. The highly invasive stem‐like phenotype was chemoresistant compared with the angiogenic phenotype. By interfering with the PI3K it was possible to sensitize tumour spheroids to chemotherapy. Real‐time quantitative polymerase chain reaction showed downregulation of the stem cell markers Nestin and Musashi‐1 in low‐generation biopsy spheroids following PI3K inhibition. Conclusions: Highly invasive tumours with a stem‐like phenotype are more chemoresistant than angiogenic tumours derived from the same patients. We suggest that treatment resistance in glioblastomas can be related to PI3K/AKT activity in stem‐like tumour cells, and that targeted interference with the PI3K/AKT pathway might differentiate and sensitize this subpopulation to chemotherapy.
A Novel Acetylenic Tricyclic bis-(Cyano Enone) Potently Induces Phase 2 Cytoprotective Pathways and Blocks Liver Carcinogenesis Induced by Aflatoxin (2008)

A novel acetylenic tricyclic bis-(cyano enone), TBE-31, is a lead compound in a series of tricyclic compounds with enone functionalities in rings A and C. Nanomolar concentrations of this potent multifunctional molecule suppress the induction of the inflammatory protein, inducible nitric oxide synthase, activate phase 2 cytoprotective enzymes in vitro and in vivo, block cell proliferation, and induce differentiation and apoptosis of leukemia cells. Oral administration of TBE-31 also significantly reduces formation of aflatoxin-DNA adducts and decreases size and number of aflatoxin-induced preneoplastic hepatic lesions in rats by >90%. Because of the two cyano enones in rings A and C, TBE-31 may directly interact with DTT and protein targets such as Keap1 that contain reactive cysteine residues. The above findings suggest that TBE-31 should also be tested for chemoprevention and chemotherapy in relevant models of cancer and against other chronic, degenerative diseases in which inflammation and oxidative stress contribute to disease pathogenesis.
High Performance Lithography Hotspot Detection With Successively Refined Pattern Identifications and Machine Learning (2011)

Under the real and evolving manufacturing conditions, lithography hotspot detection faces many challenges. First, real hotspots become hard to identify at early design stages and hard to fix at post-layout stages. Second, false alarms must be kept low to avoid excessive and expensive post-processing hotspot removal. Third, full chip physical verification and optimization require very fast turn-around time. Last but not least, rapid technology advancement favors generic hotspot detection methodologies to avoid exhaustive pattern enumeration and excessive development/update as technology evolves. To address the above issues, we propose a high performance hotspot detection methodology consisting of: 1) a fast layout analyzer; 2) powerful hotspot pattern identifiers; and 3) a generic and efficient flow with successive performance refinements. We implement our algorithms with industry-strength engine under real manufacturing conditions and show that it significantly outperforms state-of-the-art algorithms in false alarms (2.4X to 2300X reduction) and runtime (5X to 237X reduction), meanwhile achieving similar or better hotspot accuracies. Compared with pattern matching, our method achieves higher prediction accuracy for hotspots that are not previously characterized, therefore, more detection generality when exhaustive pattern enumeration is too expensive to perform a priori. Such high performance hotspot detection is especially suitable for lithography-friendly physical design.
Performance of diffused indoor optical wireless links employing neural and adaptive linear equalizers (2007)

This paper presents a comparative study of two equalizers, the adaptive linear and the neural equalizer for indoor optical wireless (OW) links. Three modulation schemes representative of a range of modulation techniques widely adopted in indoor OW systems are chosen to investigate the effectiveness of the proposed equalizers. It is shown that on-off keying (OOK) modulation technique is least affected by the multipath induced intersymbol interference (ISI), while the pulse position modulation (PPM) scheme is the most severely affected. In case of highly diffused channel, the equalized digital pulse interval modulation (DPIM) outperforms the equalized PPM and there is little or no gain in using PPM compared to OOK.
Inhibition of DNA hybridization following partial dUTP substitution. (1993)

Carry-over contamination from PCR products can yield persistent false-positive results leading to significant problems in the resolution of true positive results. Commercial kits used in many laboratories help prevent carry-over contamination. We present data on the effects of dUTP substitution on the hybridization properties of amplified DNA using alkaline phosphatase conjugated oligonucleotide probes. We observe a pronounced depression in hybridization signal intensity in some dUTP-substituted PCR products. The magnitude of the decreased hybridization signal intensity appears proportional to both the dUTP concentration in the amplification reaction and the fraction of thymidylate residues in the probe binding site. The hybridization signal is nearly eliminated from PCR products synthesized in the presence of dUTP only and where the probe binding site is particularly rich in thymidylate residues. The decrease in hybridization signal is not always restored with less stringent hybridization conditions. Conditions that permit efficient hybridization and detection of bound probe but do not compromise carry-over protection are discussed.
The Type 1 Insulin-Like Growth Factor Receptor Pathway (2008)

Research conducted over the past two decades has shown the importance of the type 1 insulin-like growth factor receptor (IGF1R) in tumorigenesis, metastasis, and resistance to existing forms of cancer therapy. The IGF1R itself has only recently been accepted as a credible treatment target, however, perhaps reflecting the potential problems for drug design posed by normal tissue IGF1R expression, and close homology with the insulin receptor. Currently approximately 12 anti-IGF1R therapeutics are undergoing clinical evaluation, including blocking antibodies and tyrosine kinase inhibitors. This review will summarize the principal signaling pathways activated by IGF1R and the preclinical data that validated this receptor as a treatment target. We will review clinical progress in the testing of IGF1R inhibitory drug candidates, the relative benefits and potential toxicities of coinhibition of the insulin receptor, and the rationale for combining IGF1R blockade with other cancer treatments. An understanding of IGF1R signaling is important because it will guide the incorporation of appropriate molecular markers into clinical trial design. This will be key to the identification of patients most likely to benefit, and so will influence the ability of IGF1R inhibition to make the transition from experimental intervention to clinical therapy.
Acidic Oligosaccharides from Pectin Hydrolysate as New Component for Infant Formulae: Effect on Intestinal Flora, Stool Characteristics, and pH (2005)

There was no difference in growth, crying, vomiting, and regurgitation patterns between the groups. In summary, acidic oligosaccharides from pectin hydrolysate are well tolerated as ingredient in infant formulae but do not affect intestinal microecology.