gebhart/patrepeval huggingface dataset:
Primary structure of beta-galactoside alpha 2,6-sialyltransferase. Conversion of membrane-bound enzyme to soluble forms by cleavage of the NH2-terminal signal anchor. (1987)

This report describes the primary structure of a rat liver beta-galactoside alpha 2,6-sialyltransferase (EC 2.4.99.1), a Golgi apparatus enzyme involved in the terminal sialylation of N-linked carbohydrate groups of glycoproteins. The complete amino acid sequence was deduced from the nucleotide sequence of cDNA clones of the enzyme. The primary structure suggests that the topology of the enzyme in the Golgi apparatus consists of a short NH2-terminal cytoplasmic domain, a 17-residue hydrophobic sequence which serves as the membrane anchor and signal sequence, and a large lumenal, catalytic domain. NH2-terminal sequence analysis of a truncated form of the enzyme, obtained by purification from tissue homogenates, reveals that it is missing a 63-residue NH2-terminal peptide which includes the membrane binding domain. These and supporting results show that soluble forms of the sialyltransferase can be generated by proteolytic cleavage between the NH2-terminal signal-anchor and the catalytic domain.
Trinucleotide cassettes increase diversity of T7 phage-displayed peptide library (2007)

The combination of T7 phage display and trinucleotide cassette randomization resulted in a novel resource for the potential isolation of binding peptides for new and previously studied molecular targets.
Understanding and detecting real-world performance bugs (2012)

Developers frequently use inefficient code sequences that could be fixed by simple patches. These inefficient code sequences can cause significant performance degradation and resource waste, referred to as performance bugs. Meager increases in single threaded performance in the multi-core era and increasing emphasis on energy efficiency call for more effort in tackling performance bugs.
Recombinant DNA-produced alpha 1-antitrypsin administered by aerosol augments lower respiratory tract antineutrophil elastase defenses in individuals with alpha 1-antitrypsin deficiency. (1989)

Alpha 1-Antitrypsin (alpha 1AT) deficiency is characterized by insufficient amounts of alpha 1AT to protect the lower respiratory tract from neutrophil elastase, resulting in emphysema. Yeast-produced recombinant alpha 1AT (rAAT) has normal antielastase function but is associated with high renal clearance, thus obviating chronic intravenous administration. As an alternative, we evaluated aerosol administration of rAAT to alpha 1AT-deficient individuals. After aerosol administration of single doses of 10-200 mg of rAAT, epithelial lining fluid (ELF) alpha 1AT antineutrophil elastase defenses were augmented in proportion to the dose of rAAT administered. ELF alpha 1AT levels and antineutrophil elastase capacity 4 h after 200 mg rAAT aerosol were increased 40-fold over preaerosol levels, and were fivefold increased over baseline at 24 h after aerosol administration. rAAT was detectable in serum after aerosol, indicating that the lower respiratory tract epithelium may be permeable to rAAT, and that aerosolized rAAT is capable of gaining access to lung interstitium. No adverse clinical effects were noted. These observations demonstrate that aerosol administration of rAAT is safe and results in significant augmentation of lung antineutrophil elastase defenses, suggesting this method is a feasible approach to therapy. Because this approach is clinically unproven, further studies will be necessary to establish the long-term clinical efficacy of aerosol therapy in alpha 1AT deficiency.
Stimulation of rabbit synoviocyte prostaglandin e2 SYNTHESIS BY LIPOPOLYSACCHARIDES AND THEIR SUBUNIT STRUCTURES (1988)

Lipopolysaccharides (LPS) induce synoviocyte activation and may lead to destruction of synovial joint tissues. We assessed the production of prostaglandin E2 (PGE2) as a measure of synoviocyte activation by LPS and their subunit structures. Diphosphoryl lipid A was the smallest portion of lipid A tested that stimulated PGE2 production. The polysaccharide fraction of LPS, containing the O antigen, was also active. Intraarticular injections of the polysaccharide resulted in a synovitis very similar to that found in association with the intact LPS molecule. These observations suggest that both parts of LPS might be involved in gram-negative, organism-associated synovitis.
Surgical Techniques for Implanting the Automatic Implantable Defibrillator (1984)

Since February 1980, the automatic defibrillator was implanted in 77 survivors of multiple cardiac arrest. The subxiphoid technique was used in 28 patients and the thoracotomy technique was used in 20 patients with previous cardiac surgery. Median sternotomy was used in 29 patients undergoing open heart procedures as well as defibrillator implantation. While the subxiphoid is the most benign procedure employed, all are safe and well tolerated. The method used is determined by the clinical picture. Survival studies indicate improved survival in this high risk population.
Cosignaling Complexity Gets More Convoluted: The Emerging Importance of the B7-Like Butyrophilin Family of Immune Regulators (2008)

Activation of T cells is known to be modulated by positive or negative co-signaling molecules. The B7-family of costimulatory molecules has received the greatest attention in the past, and intervention in B7-family signaling pathways has proven to be an efficacious strategy for treating autoimmune diseases in the clinic. In recent months a new family of molecules has garnered interest -- the butyrophilins -- and early data is suggesting that these butyrophilin and butyrophilin- like molecules have the potential for influencing the nature of immune and inflammatory responses. In vitro studies have revealed that butyrophilins, such as butyrophilin-like 2 (BTNL2), can negatively regulate T cell proliferation and cytokine production. Additionally, genetic studies have described polymorphisms in BTNL2 which are reported to be associated with disorders such as sarcoidosis, myositis and ulcerative colitis. The potential for interdicting the butyrophilin pathways highlights potential opportunities for developing new therapeutic strategies for treating autoimmune and inflammatory disorders. This review will focus on the emerging information of this new class of regulatory molecules.
P-glycoprotein (1995)

P-glycoprotein consists of two homologous halves, each composed of a transmembrane domain and a nucleotide-binding domain. In order to understand how the domains interact in P-glycoprotein, we expressed each domain as a separate polypeptide and tested for associations using coimmunoprecipitation assays. We found that the interactions between the two halves of P-glycoprotein were mediated through associations between the two transmembrane domains as well as through the nucleotide-binding domains. In addition, the nucleotide-binding domain also associated with the transmembrane domain in each half of the molecule. By contrast, we could not detect any association either between the first nucleotide-binding domain and the second transmembrane domain, or between the second nucleotide-binding domain and the first transmembrane domain. We then tested whether individual domains associated with molecular chaperones, since biogenesis of P-glycoprotein appears to involve the chaperones calnexin and Hsc70. We found that calnexin associated only with the transmembrane domains, while Hsc70 associated only with the nucleotide-binding domains. These results suggest that noncovalent interaction between the domains of P-glycoprotein can contribute to structure and function of P-glycoprotein and that chaperones may participate in the folding of each domain.
Short antibacterial peptides and erythromycin act synergically against Escherichia coli (2001)

Five different peptides (6-18 residues) with chain lengths shorter than the required minimum to span the bacterial cell membrane as monomeric helices were designed in order to elucidate whether variation in chain length exerted differences in their mode of action. To gain a better understanding of the possible mode of action of these peptides, they were studied in combination with clinically used antibiotics with different targets. Antibiotic-peptide combinations were tested against Escherichia coli ATCC 25922 and Staphylococcus aureus ATCC 25923. No synergy was observed between the peptides and antibiotics when tested against S. aureus. Synergic interactions between all peptides and erythromycin were observed when tested against E. coli. Synergy was also observed with rifampicin and two peptides against E. coli. There was no clear-cut correlation between the ability to interact synergically or antagonistically and the number of residues. We further investigated the combined action of our peptides and PGLa, to elucidate peptide-peptide interactions. In contrast to previously reported synergy between magainin 2 and PGLa, our peptides did not show any synergy when combined with PGLa. Thus, our results indicate an alternative mode of action of these antibacterial peptides as compared with peptides such as magainin 2.
Large Magnetoresistance at Room Temperature in Ferromagnetic Thin Film Tunnel Junctions (1995)

Ferromagnetic-insulator-ferromagnetic tunneling has been measured in CoFe $/$A${\mathrm{l}}_{2}$${\mathrm{O}}_{3}$ $/$Co or NiFe junctions. At 295, 77, and 4.2 K the fractional change in junction resistance with magnetic field, $\ensuremath{\Delta}R/R$, is 11.8%, 20%, and 24%, respectively. The value at 4.2 K is consistent with Julliere's model based on the spin polarization of the conduction electrons of the magnetic films. $\ensuremath{\Delta}R/R$ changes little with a small voltage bias, whereas it decreases significantly at higher bias $(&gt;0.1\mathrm{V})$, in qualitative agreement with Slonczewski's model. These junctions have potential use as low-power field sensors and memory elements.
Power Spectrum of Light Scattered by Two-Level Systems (1969)

The power spectrum of the light scattered by a two-level atom driven near resonance by a monochromatic classical electric field is evaluated. The atom is assumed to relax to equilibrium with the driving field via radiation damping, which is treated by explicitly coupling the atom to the quantized electromagnetic field modes. The power spectrum of the scattered field is directly obtainable from the two-time atomic dipole moment correlation function, which is evaluated by a method based on a Markoff-type assumption analogous to that used to evaluate the time evolution of single-time atomic expectation values.
Charge-Transporting Molecular Glasses (2002)

Among organic materials vitrification for many years was regarded mainly as a privilege of polymers. However, recently a lot of attention is paid to organic low molar mass compounds that readily form glasses above room temperature. Such compounds are called molecular glasses or amorphous molecular materials. Among these materials the most widely studied are charge-transporting molecular glasses used in copiers and laser printers, organic light-emitting diodes, photovoltaic devices, and as photorefractive materials. Two types of molecular glasses, i.e., p-type (hole-transporting), and n-type (electron-transporting) are discussed. Work of the laboratories of the authors is emphasized. In addition, an overview of current and potential applications for these materials is presented.
Smooth muscle stem cells (2003)

Vascular smooth muscle cells (SMCs) originate from multiple types of progenitor cells. In the embryo, the most well studied SMC progenitor is the cardiac neural crest stem cell. Smooth muscle differentiation in the neural crest lineage is controlled by a combination of cell intrinsic factors, including Pax3, Tbx1, FoxC1, and serum response factor, interacting with various extrinsic factors in the local environment such as bone morphogenetic proteins (BMPs), Wnts, endothelin (ET)-1, and FGF8. Additional sources of multipotential cells that give rise to vascular SMCs in the embryo include proepicardial cells and possibly endothelial progenitor cells. In the adult, vascular SMCs must continually repair arterial injuries and maintain functional mass in response to changing demands upon the vessel wall. Recent evidence suggests that this is accomplished, in part, by recruiting multipotential vascular progenitors from bone marrow-derived stem cells as well as from less well defined sources within adult tissues themselves. This article will review our current understanding of the origins of vascular SMCs from multipotential stem and progenitor cells in developing as well as adult vasculature.
Clinical efficacy and safety of statins in managing cardiovascular risk (2008)

Since their introduction in the 1980s, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) have emerged as the one of the best-selling medication classes to date, with numerous trials demonstrating powerful efficacy in preventing cardiovascular outcomes. As our understanding of low-density lipoprotein cholesterol (LDL-C) and atherosclerosis continues to grow, the concept of 'lower is better' has corresponded with a more is better' approach to statin-based therapy. This review provides a detailed understanding of the clinical efficacy and safety of statins with a particular emphasis on the third generation drug, rosuvastatin.
In vivo maturation of human frataxin (2007)

The defective expression of frataxin causes the hereditary neurodegenerative disorder Friedreich's ataxia (FRDA). Human frataxin is synthesized as a 210 amino acid precursor protein, which needs proteolytic processing into mitochondria to be converted into the functional mature form. In vitro processing of human frataxin was previously described to yield a 155 amino acid mature form, corresponding to residues 56-210 (frataxin(56-210)). Here, we studied the maturation of frataxin by in vivo overexpression in human cells. Our data show that the main form of mature frataxin is generated by a proteolytic cleavage between Lys80 and Ser81, yielding a 130 amino acid protein (frataxin(81-210)). This maturation product corresponds to the endogenous frataxin detected in human heart, peripheral blood lymphocytes or dermal fibroblasts. Moreover, we demonstrate that frataxin(81-210) is biologically functional, as it rescues aconitase defects in frataxin-deficient cells derived from FRDA patients. Importantly, our data indicate that frataxin(56-210) can be produced in vivo when the primary 80-81 maturation site is unavailable, suggesting the existence of proteolytic mechanisms that can actively control the size of the mature product, with possible functional implications.
Interaction of cytopathogenic toxin from Clostridium difficile with cells in tissue culture. (1980)

Partially purified cytopathogenic toxin from Clostridium difficile induced morphological changes in five cell lines in tissue culture. The relative sensitivity scale of the cell lines was human lung and intestinal fibroblasts greater than Chinese hamster ovary cells much greater than mouse adrenal cells greater than mouse neuroblastoma cells. The cytopathogenic effect did not occur in toxin-treated lung fibroblasts incubated at 0 degree C. Pre-incubation of lung fibroblasts with 2,4-dinitrophenol prevented the cytopathogenic effect. The toxin bound to as yet unidentified receptors at the surface of human lung and intestinal fibroblasts. The toxin-induced morphological (actinomorphic) changes in lung and intestinal fibroblasts closely resembled the effects induced by the fungal metabolite cytochalasin B (CB), which is known to disrupt microfilaments reversibly. Indirect immunofluorescence with anti-actin antiserum demonstrated that the C. difficile toxin disrupted the straight actin filament bundles seen in normal fibroblasts. The cytopathogenic effect became apparent 3--5 h after exposure to toxin. However, irreversible intoxication occurred already within 20 min of exposure, as toxin-treated fibroblasts which were trypsinized and reseeded were not able to attach to the solid substratum and regenerate their typical shape, a process requiring reorganization of actin into microfilament bundles. Two possible different modes of action of the toxin, leading to microfilament disruption, are suggested: 1) Transmembrane signal by surface-bound toxin via microfilament-linked integral membrane protein(s) and 2) Penetration of surface-bound whole toxin or an active fragment, followed by its intracellular action. The experimental evidence so far is consistent with either of these mechanisms.
Flagellin A is essential for the virulence of Vibrio anguillarum (1996)

A flagellin gene from the fish pathogen Vibrio anguillarum was cloned, sequenced, and mutagenized. The DNA sequence suggests that the flaA gene encodes a 40.1-kDa protein and is a single transcriptional unit. A polar mutation and four in-frame deletion mutations (180 bp deleted from the 5' end of the gene, 153 bp deleted from the 3' end of the gene, a double deletion of both the 180- and 153-bp deletions, and 942 bp deleted from the entire gene) were made. Compared with the wild type, all mutants were partially motile, and a shortening of the flagellum was seen by electron microscopy. Wild-type phenotypes were regained when the mutations were transcomplemented with the flaA gene. Protein analysis indicated that the flaA gene corresponds to a 40-kDa protein and that the flagellum consists of three additional flagellin proteins with molecular masses of 41, 42, and 45 kDa. N-terminal sequence analysis confirmed that the additional proteins were flagellins with N termini that are 82 to 88% identical to the N terminus of FlaA. Virulence studies showed that the N terminal deletion, the double deletion, and the 942-bp deletion increased the 50% lethal dose between 70- and 700-fold via immersion infection, whereas infection via intraperitoneal injection showed no loss in virulence. In contrast, the polar mutant and the carboxy-terminal deletion mutant showed approximately a 10(4)-fold increase in the 50% lethal dose by both immersion and intraperitoneal infection. In summary, FlaA is needed for crossing the fish integument and may play a role in virulence after invasion of the host.
Human chronic myelogenous leukemia cell-line with positive Philadelphia chromosome (1975)

A cell-line derived from a patient with chronic myelogenous leukemia (CML) is described. The new cell-line, which has over 175 serial passanges in a 3 1/2-yr period, has the following characteristics: (1) CML cells started to proliferate actively since they were first incubated in culture media. A threefold increase in the total number of cells was observed during the first seven passages; the cell population increased by a factor of 10 to 20 every 7 days from passage 8 through 85; from 20 to 40 times from passage 86 through 150, and more than 40 times after 150 passages. (2) The majority of the nononucleated cells are undifferentiated blasts. (3) The karyotype of all the cells examined show the Philadelphia (Ph1) chromosome and a long acrocentric marker plus aneuploidy. The Giemsa-banding studies identified the Ph1 chromosome as a terminal deletion of the long arm of chromosome 22:del(22)(q12) and the long acrocentric marker as an unbalanced reciprocal translocation of one chromosome 17 and the long arm of one chromosome 15. (4) The CML cells do not produce immunoglobulins, are free of mycoplasma, Epstein-Barr virus, and herpes-like virus particles. (5) CML cells have no alkaline phosphatase and myeloperoxidase activities and did not engulf inert particles. (6) Cultured CML cells provide a constant source of a specific antigen. This CML cell-line represents a unique source of CML cells with meaningful indicators of malignancy for clinical and experimental studies.
731. High-Fidelity CRISPR-Cas9 Nucleases with No Detectable Genome-Wide Off-Target Effects (2016)

CRISPR-Cas9 nucleases are widely used for genome editing but can induce unwanted off-target mutations at genomic locations that resemble the intended target. These so-called off-target effects can confound research applications and are important considerations for potential therapeutic use. Existing strategies for reducing genome-wide off-targets of the broadly used Streptococcus pyogenes Cas9 (SpCas9) have thus far proven to be imperfect by possessing only partial efficacy and/or other limitations that constrain their use. Here we describe a high-fidelity variant of SpCas9, called SpCas9-HF1, that contains alterations in the amino acid sequence designed to reduce non-specific contacts to the target strand DNA. SpCas9-HF1 retains on-target activities comparable to wild-type SpCas9 with >85% of the 37 single-guide RNAs (sgRNAs) tested in human cells. Strikingly, with eight different sgRNAs targeted to standard non-repetitive sequences in human cells, SpCas9-HF1 rendered all or nearly all off-target events imperceptible by genome-wide break capture and targeted sequencing methods. Even for atypical, repetitive target sites, the vast majority of off-targets induced by SpCas9-HF1 were not detected. With its exceptional precision, SpCas9-HF1 provides an important and easily employed alternative to wild-type SpCas9 that can eliminate off-target effects when using CRISPR-Cas9 for research and therapeutic applications. Our findings also suggest a general strategy for improving or optimizing the genome-wide specificities of other Cas9 orthologues and engineered variants.
Urinary p75ECD (2017)

The assay for urinary p75<sup>ECD</sup> is analytically robust and shows promise as an ALS biomarker with prognostic, disease progression, and potential pharmacodynamic application. Baseline urinary p75<sup>ECD</sup> provides prognostic information and is currently the only biological fluid-based biomarker of disease progression.
Minimizing Estimation Runtime on Noisy Quantum Computers (2021)

The number of measurements demanded by hybrid quantum-classical algorithms such as the variational quantum eigensolver (VQE) is prohibitively high for many problems of practical value. For such problems, realizing quantum advantage will require methods that dramatically reduce this cost. Previous quantum algorithms that reduce the measurement cost (e.g., quantum amplitude and phase estimation) require error rates that are too low for near-term implementation. Here we propose methods that take advantage of the available quantum coherence to maximally enhance the power of sampling on noisy quantum devices, reducing the measurement number and runtime compared to the standard sampling method of the VQE. Our scheme derives inspiration from quantum metrology, phase estimation, and the more recent "alpha-VQE" proposal, arriving at a general formulation that is robust to error and does not require ancilla qubits. The central object of this method is what we call the "engineered likelihood function" (ELF), used for carrying out Bayesian inference. We show how the ELF formalism enhances the rate of information gain in sampling as the physical hardware transitions from the regime of noisy intermediate-scale quantum computers to that of quantum error-corrected ones. This technique speeds up a central component of many quantum algorithms, with applications including chemistry, materials, finance, and beyond. Similar to the VQE, we expect small-scale implementations to be realizable on today's quantum devices.