gebhart/patrepeval huggingface dataset:
High-Speed Atomic Force Microscopy for Studying the Dynamic Behavior of Protein Molecules at Work (2006)

In the quest for the mechanism of protein functions, various key techniques and instruments have been developed. This is an era when scrutinizing a certain protein from various angles is becoming possible through combined knowledge of its structure and function. However, it is necessary to link these different aspects of a protein along a time axis, but no technology is available for tracing a protein in action, at high spatial and temporal resolutions. Atomic force microscopy made it possible for the first time to view a nanometer-scale world in an aqueous environment. In 2001, we developed the first-generation high-speed atomic force microscope (AFM) that could capture moving protein molecules on video at 80 ms/frame. Since then, we have been carrying out various efforts to increase its scan rate as well as to substantially reduce tip–sample interaction force. The reduction in this force is a key to making the high-speed AFM practically useful in life sciences. Various new techniques and devices developed in the past four years have brought the AFM to its second-generation stage. It can now capture weakly interacting protein molecules successively without disturbing their physiological function. Here, we report our efforts made over the past four years, the present capacity of the high-speed AFM, and our preliminary work on the next generation of the instrument.
Innovations in time (2007)

Victor Aarre, Henrik Juhl Hansen, Jörg Herwanger, Julie Marshall, Jens Olav Paulsen, Stephen Pickering, and Michael Tang of WesternGeco describe the company’s experience with time-lapse (4D) seismic using its proprietary Q-Marine technology. Time-lapse or 4D seismic technology has existed for quite some time; the first 4D seismic survey was acquired in 1981 onshore Canada. Today, 16% of Q-Marine single-sensor seismic surveys are related to the monitoring of reservoir production. One reason for the growth of seismic reservoir monitoring programmes is that, in the last five years, the industry has responded to 4D seismic imaging challenges through a number of significant enhancements in repeatability. This, combined with innovations in 4D analysis and interpretation, has caused time-lapse seismic technology to become an integral part of the business process of many oil companies.
The ubiquitin‐proteasome pathway and proteasome inhibitors (2001)

The ubiquitin-proteasome pathway has emerged as a central player in the regulation of several diverse cellular processes. Here, we describe the important components of this complex biochemical machinery as well as several important cellular substrates targeted by this pathway and examples of human diseases resulting from defects in various components of the ubiquitin-proteasome pathway. In addition, this review covers the chemistry of synthetic and natural proteasome inhibitors, emphasizing their mode of actions toward the 20S proteasome. Given the importance of proteasome-mediated protein degradation in various intracellular processes, inhibitors of this pathway will continue to serve as both molecular probes of major cellular networks as well as potential therapeutic agents for various human diseases.
Spin Echoes (1950)

Intense radiofrequency power in the form of pulses is applied to an ensemble of spins in a liquid placed in a large static magnetic field ${H}_{0}$. The frequency of the pulsed r-f power satisfies the condition for nuclear magnetic resonance, and the pulses last for times which are short compared with the time in which the nutating macroscopic magnetic moment of the entire spin ensemble can decay. After removal of the pulses a non-equilibrium configuration of isochromatic macroscopic moments remains in which the moment vectors precess freely. Each moment vector has a magnitude at a given precession frequency which is determined by the distribution of Larmor frequencies imposed upon the ensemble by inhomogeneities in ${H}_{0}$. At times determined by pulse sequences applied in the past the constructive interference of these moment vectors gives rise to observable spontaneous nuclear induction signals. The properties and underlying principles of these spin echo signals are discussed with use of the Bloch theory. Relaxation times are measured directly and accurately from the measurement of echo amplitudes. An analysis includes the effect on relaxation measurements of the self-diffusion of liquid molecules which contain resonant nuclei. Preliminary studies are made of several effects associated with spin echoes, including the observed shifts in magnetic resonance frequency of spins due to magnetic shielding of nuclei contained in molecules.
Haptoglobin improves shock, lung injury, and survival in canine pneumonia (2018)

During the last half-century, numerous antiinflammatory agents were tested in dozens of clinical trials and have proven ineffective for treating septic shock. The observation in multiple studies that cell-free hemoglobin (CFH) levels are elevated during clinical sepsis and that the degree of increase correlates with higher mortality suggests an alternative approach. Human haptoglobin binds CFH with high affinity and, therefore, can potentially reduce iron availability and oxidative activity. CFH levels are elevated over approximately 24-48 hours in our antibiotic-treated canine model of S. aureus pneumonia that simulates the cardiovascular abnormalities of human septic shock. In this 96-hour model, resuscitative treatments, mechanical ventilation, sedation, and continuous care are translatable to management in human intensive care units. We found, in this S. aureus pneumonia model inducing septic shock, that commercial human haptoglobin concentrate infusions over 48-hours bind canine CFH, increase CFH clearance, and lower circulating iron. Over the 96-hour study, this treatment was associated with an improved metabolic profile (pH, lactate), less lung injury, reversal of shock, and increased survival. Haptoglobin binding compartmentalized CFH to the intravascular space. This observation, in combination with increasing CFHs clearance, reduced available iron as a potential source of bacterial nutrition while decreasing the ability for CFH and iron to cause extravascular oxidative tissue injury. In contrast, haptoglobin therapy had no measurable antiinflammatory effect on elevations in proinflammatory C-reactive protein and cytokine levels. Haptoglobin therapy enhances normal host defense mechanisms in contrast to previously studied antiinflammatory sepsis therapies, making it a biologically plausible novel approach to treat septic shock.
CCAAT/Enhancer Binding Protein α (C/EBPα) in Adipose Tissue Regulates Genes in Lipid and Glucose Metabolism and a Genetic Variation in C/EBPα Is Associated with Serum Levels of Triglycerides (2008)

Adipose tissue C/EBPalpha regulates several genes in glucose and lipid metabolism, and a genetic variation in C/EBPalpha is associated with triglycerides in two independent populations.
Determination of a Track's Edge by Differential Power Spectrum (1992)

We show experimentally that the transverse edge of recorded data can be determined by spatially differentiating the readback power spectrum with respect to the displacement of the recording head. This was accomplished using straightforward signal processing described here as the differential power spectrum. This technique can be applied to data tracks having pseudorandom data even in systems not possessing guard bands. We describe a multi-element head structure which may be used to exploit this phenomenon to realize a new continuously monitored track following servo system.
ChemInform Abstract: Conformationally Restricted Amino Acids and Dipeptides, (non) Peptidomimetics and Secondary Structure Mimetics (1994)

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.
Secure short-cut routing for mobile IP (1994)

This paper describes the architecture and implementation of a mobile IP system. It allows mobile hosts to roam between cells implemented with 2-Mbps radio base stations, while maintaining Internet connectivity. The system is being developed as part of a course on wireless networks at Harvard and has been operational since March 1994. The architecture scales well, both geographically and in the number of mobile hosts supported. It supports secure short-cut routing to mobile hosts using the existing Internet routing system without change. The implementation demonstrates a robust, low complexity realization of the architecture, and provides trade-off opportunities between efficiency and cost. Measured performance of the mobile system is generally excellent. The system can handle a high rate of location updates, and routes packets almost as efficiently for mobile hosts as the Internet does for stationary hosts. We observe reasonable TCP behavior during hand-offs. 1.
Antibody-mediated Remyelination: Relevance to Multiple Sclerosis (2000)

Intravenous immunoglobulin (IVIG) is widely used for treatment of autoimmune neurological disorders and is currently in clinical trials as a therapy for multiple sclerosis. We have previously demonstrated that certain mouse monoclonal antibodies of the IgM isotype, promote significant remyelination when administered to mice with chronic Theiler's murine encephalomyelitis virus-induced demyelinating disease. These IgM antibodies bind to antigens expressed on oligodendrocytes. We now demonstrate that polyclonal human IgG (IVIG) and polyclonal human IgM also promote remyelination in this system. Although both polyclonal human IgG and IgM promote remyelination, IgM is more potent. Polyclonal human IgM also differs from human IgG in its ability to bind strongly to antigens expressed in the CNS and by oligodendrocytes. We propose that polyclonal IgG and polyclonal IgM may function to promote remyelination by different mechanisms. IVIG may function based on its immunomodulatory activity, while the activity of IgM is critically dependent upon its reactivity with CNS antigens. This possibility has clear relevance to the use of antibodies as a therapy for multiple sclerosis, suggesting that combined treatment with antibodies exerting immunomodulatory activity, in concert with antibodies that function through direct binding to CNS antigens, may synergize to enhance the efficacy of the therapy.
A New Tri-Fab Bispecific Antibody for Pretargeting Trop-2–Expressing Epithelial Cancers (2012)

TF12 was retained sufficiently on the cell surface in several epithelial cancers, thereby making it suitable for pretargeted imaging and therapy of various Trop-2-expressing carcinomas.
Self-Assembly and Mineralization of Peptide-Amphiphile Nanofibers (2001)

We have used the pH-induced self-assembly of a peptide-amphiphile to make a nanostructured fibrous scaffold reminiscent of extracellular matrix. The design of this peptide-amphiphile allows the nanofibers to be reversibly cross-linked to enhance or decrease their structural integrity. After cross-linking, the fibers are able to direct mineralization of hydroxyapatite to form a composite material in which the crystallographic c axes of hydroxyapatite are aligned with the long axes of the fibers. This alignment is the same as that observed between collagen fibrils and hydroxyapatite crystals in bone.
The Toxicology of Interleukin-12: A Review (1999)

Recombinant murine interleukin (IL)-12 (rmIL-12) exhibits antitumor, antiviral, and antimicrobial activities and can modify allergic inflammatory reactions in animal models. Recombinant human IL-12 (rhIL-12) is currently in clinical trials for treatment of cancer, asthma, and viral hepatitis. Principally a phagocyte-derived cytokine, IL-12 targets natural killer cells and T lymphocytes, stimulating their activity and the secretion of interferon (IFN)-gamma. An understanding of the toxicology of IL-12, due in part to effects mediated by IFN-gamma, has emerged from preclinical safety and mechanistic studies and initial clinical trials. Target organs common to several animal species and humans include the lymphohematopoietic system, intestines, liver, and lung.
Independence of cyclic AMP and relA gene stimulation of glycogen synthesis in intact Escherichia coli cells (1985)

Previous studies from our laboratory established that in Escherichia coli, glycogen synthesis is regulated by both the relA gene, which mediates the stringent response, and by cyclic AMP. However, those studies raised the question of whether this dual regulatory system functions in an independent or a dependent manner. We show here that this regulation is independent, i.e., each regulatory process can express its action in the absence of the other. Triggering the stringent response by amino acid starvation increased glycogen synthesis even in mutants lacking the ability to synthesize cyclic AMP or lacking cyclic AMP receptor protein; and cyclic AMP addition stimulated glycogen synthesis in relA mutant strains. We also show that physiological concentrations of GTP inhibit ADP-glucose synthetase (glucose-1-phosphate adenylyltransferase, EC 2.7.7.27), the rate-limiting enzyme of bacterial glycogen synthesis, in vitro. Because the stringent response is known to cause an abrupt decrease in the cellular level of GTP, modulation of ADP-glucose synthetase activity by this nucleotide could account for a substantial portion of the step-up in the cellular rate of glycogen synthesis observed when the stringent response is triggered.
Insertional inactivation of staphylococcal methicillin resistance by Tn551 (1983)

Transposon Tn551 was translocated into the chromosome of a methicillin-resistant (mec) strain of Staphylococcus aureus by heat inactivation of a thermo-sensitive plasmid carrying Tn551 and selection for erythromycin-resistant (Emr) survivors. Two independent chromosomal insertions of Tn551 were obtained which reduced the level of the methicillin resistance by a factor of 50 to 100, making the strains phenotypically methicillin sensitive (Mecs). Each of the Tn551 insertions was on the largest fragment produced by EcoRI digestion of the chromosomal DNA of these strains. The integration sites lie about 1 kilobase apart. These Mecs strains reverted to Mecr at frequencies of 2.4 X 10(-8) and 3.6 X 10(-5), respectively. The majority of Mecr revertants still were Emr; only a few lost the Emr phenotype concomitantly with reversion to the Mecr phenotype. Hybridization data with labeled Tn551 showed complex rearrangements and deletions in the region of the insertion. These two Tn551 insertions do not lie on the same linkage group, II, as the mec determinant. The phenotypic expression of methicillin resistance, therefore, is also dependent upon a chromosomal genetic marker not physically linked to the mec determinant.
Feeding suppression by fibroblast growth factor‐1 is accompanied by selective induction of heat shock protein 27 in hypothalamic astrocytes (2001)

It has been suggested that fibroblast growth factor (FGF)-1 serves as a physiological satiety factor in the hypothalamus, although the molecular mechanism underlying such a function is poorly understood. To gain additional insight into this issue, we used a Sendai virus (SeV) gene expression system in rats to explore genes differentially expressed subsequent to expression of FGF-1. Using cDNA arrays, we determined that infusion of FGF-1/SeV into one lateral ventricle induced selective expression of heat shock protein (HSP) 27 in the hypothalamus. Whereas FGF-1 expression was restricted to the ependymal cell layer of the cerebral ventricles, HSP27 was more widely expressed in astrocytes residing in the surrounding periventricular region. Similarly, infusion of FGF-1 polypeptide into a lateral ventricle induced dose-dependent HSP27 expression in periventricular astrocytes surrounding the third ventricle, with maximum mRNA levels being attained 6 h after infusion. This induction of HSP27 was accompanied by a significant suppression of feeding behaviour. Interestingly, suppression of feeding caused by intracerebro ventricular infusion of ciliary neurotrophic factor was also accompanied by induction of HSP27 in periventricular astrocytes, but suppression of feeding caused by infusion of leptin was not. It therefore appears that suppression of feeding by FGF-1 is accompanied by selective induction of HSP27 expression in hypothalamic astrocytes surrounding the third ventricle, and that this response may be a key component of the mechanism by which appetite is regulated by FGF-1.
Pathways of Degradation and Mechanism of Action of Antisense Oligonucleotides in Xenopus laevis Embryos (1991)

Recently, we described a new class of antisense oligonucleotides that can be used to direct the cleavage of mRNAs in Xenopus laevis embryos by RNase H (Dagle et al., Nucleic Acids Res. 18, 4751-4757). In this study, we have examined several factors that determine the activity of these derivatives. In embryos, oligodeoxyribonucleotides were found to be rapidly degraded by a 3' exonuclease. Modification of 3'-terminal phosphodiester linkages as phosphoramidates blocks this activity. The predominant sites of endonucleolytic cleavage within the embryo are localized close to the 5' termini demonstrating the necessity of multiply modifying phosphodiester linkages at each end of the molecule. A stretch of at least six consecutive phosphodiester linkages is required to form an effective substrate for Xenopus RNase H; mRNA degradation with an oligonucleotide containing fewer than six contiguous unmodified internucleoside linkages is greatly diminished. Injection of an anti-cyclin B oligonucleotide containing eight unmodified residues results in degradation of cyclin B mRNAs and subsequent inhibition of embryonic cell division. An oligonucleotide with the same sequence but containing four consecutive phosphodiesters has no observable effect on the cell cycle. This last observation suggests that, in Xenopus embryos, hybridization alone has a limited role, if any, in oligonucleotide-mediated inhibition of gene expression.
Combined gamma-tocotrienol and erlotinib/gefitinib treatment suppresses Stat and Akt signaling in murine mammary tumor cells. (2010)

Combined treatment of gamma-tocotrienol with erlotinib or gefitinib prevents ErbB receptor heterodimer cooperation and inhibits EGF-dependent mitogenic signaling in +SA murine mammary tumor cells. These findings strongly suggest that combination treatment may significantly improve therapeutic responsiveness in breast cancer patients.
Cell-free DNA fragment-size distribution analysis for non-invasive prenatal CNV prediction (2016)

Our source code is available on GitHub at https://github.com/compbio-UofT/FSDA CONTACT: : brudno@cs.toronto.edu.
Bacterial abundance and diversity in pond water supplied with different feeds (2016)

Abstract The abundance and diversity of bacteria in two types of ponds were investigated by quantitative PCR and Illumina MiSeq sequencing. The results revealed that the abundance of bacterial 16S rRNA genes in D ponds (with grass carp fed sudan grass) was significantly lower than that in E ponds (with grass carp fed commercial feed). The microbial communities were dominated by Proteobacteria , Cyanobacteria , Bacteroidetes , and Actinobacteria in both E and D ponds, while the abundance of some genera was significantly different between the two types of ponds. Specifically, some potential pathogens such as Acinetobacter and Aeromonas were found to be significantly decreased, while some probiotics such as Comamonadaceae unclassified and Bacillales unclassified were significantly increased in D ponds. In addition, water quality of D ponds was better than that of E ponds. Temperature, dissolved oxygen and nutrients had significant influence on bacterial communities. The differences in bacterial community compositions between the two types of ponds could be partially explained by the different water conditions.
A viral member of the ERV1/ALR protein family participates in a cytoplasmic pathway of disulfide bond formation (2000)

Proteins of the ERV1/ALR family are encoded by all eukaryotes and cytoplasmic DNA viruses for which substantial sequence information is available. Nevertheless, the roles of these proteins are imprecisely known. Multiple alignments of ERV1/ALR proteins indicated an invariant C-X-X-C motif, but no similarity to the thioredoxin fold was revealed by secondary structure predictions. We chose a virus model to investigate the role of these proteins as thiol oxidoreductases. When cells were infected with a mutant vaccinia virus in which the E10R gene encoding an ERV1/ALR family protein was repressed, the disulfide bonds of three other viral proteins-namely, the L1R and F9L proteins and the G4L glutaredoxin-were completely reduced. The same outcome occurred when Cys-43 or Cys-46, the putative redox cysteines of the E10R protein, was mutated to serine. These two cysteines were disulfide bonded during a normal virus infection but not if the synthesis of other viral late proteins was inhibited or the E10R protein was expressed by itself in uninfected cells, suggesting a requirement for an upstream viral thiol oxidoreductase. Remarkably, the cysteine-containing domains of the E10R and L1R viral membrane proteins and the glutaredoxin are in the cytoplasm, in which assembly of vaccinia virions occurs, rather than in the oxidizing environment of the endoplasmic reticulum. These data indicated a viral pathway of disulfide bond formation in which the E10R protein has a central role. By extension, the ERV1/ALR family may represent a ubiquitous class of cellular thiol oxidoreductases that interact with glutaredoxins or thioredoxins.
Multifunctional Polymeric Micelles as Cancer-Targeted, MRI-Ultrasensitive Drug Delivery Systems (2006)

We describe the development of multifunctional polymeric micelles with cancer-targeting capability via alpha(v)beta(3) integrins, controlled drug delivery, and efficient magnetic resonance imaging (MRI) contrast characteristics. Doxorubicin and a cluster of superparamagnetic iron oxide (SPIO) nanoparticles were loaded successfully inside the micelle core. The presence of cRGD on the micelle surface resulted in the cancer-targeted delivery to alpha(v)beta(3)-expressing tumor cells. In vitro MRI and cytotoxicity studies demonstrated the ultrasensitive MRI imaging and alpha(v)beta(3)-specific cytotoxic response of these multifunctional polymeric micelles.