gebhart/patrepeval huggingface dataset:
Parallel analysis of oligodeoxyribonucleotide (oligonucleotide) interactions. I. Analysis of factors influencing oligonucleotide duplex formation (1992)

A novel method for the analysis of oligonucleotide-oligonucleotide interactions is described. Oligonucleotides of different sequence are synthesised in situ as stripes on the surface of a glass slide (see accompanying paper). Multiple hybridizations are then carried out on each oligonucleotide simultaneously to determine the dependence of oligonucleotide duplex formation on duplex length, base composition, hybridisation solvent and sequence complexity.
Engineering stability into Escherichia coli secreted Fabs leads to increased functional expression (2006)

The recombinant expression of immunoglobulin domains, Fabs and scFvs in particular, in Escherichia coli can vary significantly from antibody to antibody. We hypothesized that poor Fab expression is often linked to poor intrinsic stability. To investigate this further, we applied a novel approach for stabilizing a poorly expressing anti-tetanus toxoid human Fab with a predisposition for being misfolded and non-functional. Forty-five residues within the Fab were chosen for saturation mutagenesis based on residue frequency analysis and positional entropy calculations. Using automated screening, we determined the approximate midpoint temperature of thermal denaturation (TM) for over 4000 library members with a maximum theoretical diversity of 855 unique mutations. This dataset led to the identification of 11 residue positions, primarily in the Fv region, which when mutated enhanced Fab stability. By combining these mutations, the TM of the Fab was increased to 92 degrees C. Increases in Fab stability correlated with higher expressed Fab yields and higher levels of properly folded and functional protein. The mutations were selected based on their ability to increase the apparent stability of the Fab and therefore the exact mechanism behind the enhanced expression in E.coli remains undefined. The wild-type and two optimized Fabs were converted to an IgG1 format and expressed in mammalian cells. The optimized IgG1 molecules demonstrated identical gains in thermostability compared to the Fabs; however, the expression levels were unaffected suggesting that the eukaryotic secretion system is capable of correcting potential folding issues prevalent in E.coli. Overall, the results have significant implications for the bacterial expression of functional antibody domains as well as for the production of stable, high affinity therapeutic antibodies in mammalian cells.
Analysis of Pars Plana Vitrectomy for Optic Pit–Related Maculopathy With Intraoperative Optical Coherence Tomography (2011)

Optimal management of optic pit-related maculopathy remains to be determined. The fluid source for the maculopathy also remains controversial. In this article, we present a unique surgical technique for internal drainage of the intraretinal fluid and describe the intraoperative use of spectral-domain optical coherence tomography to assist in the surgical management of this condition. Pars plana vitrectomy was performed with elevation of the posterior hyaloid. Following an air-fluid exchange, aspiration over the optic nerve pit was performed. Following aspiration, intraoperative spectral-domain optical coherence tomography demonstrated collapse of the retinoschisis, strongly suggesting a connection between the vitreous cavity and the intraretinal fluid.
Systematic approaches to identify E3 ligase substrates (2016)

Protein ubiquitylation is a widespread post-translational modification, regulating cellular signalling with many outcomes, such as protein degradation, endocytosis, cell cycle progression, DNA repair and transcription. E3 ligases are a critical component of the ubiquitin proteasome system (UPS), determining the substrate specificity of the cascade by the covalent attachment of ubiquitin to substrate proteins. Currently, there are over 600 putative E3 ligases, but many are poorly characterized, particularly with respect to individual protein substrates. Here, we highlight systematic approaches to identify and validate UPS targets and discuss how they are underpinning rapid advances in our understanding of the biochemistry and biology of the UPS. The integration of novel tools, model systems and methods for target identification is driving significant interest in drug development, targeting various aspects of UPS function and advancing the understanding of a diverse range of disease processes.
Roles of FGFs as Adipokines in Adipose Tissue Development, Remodeling, and Metabolism (2014)

White and brown adipose tissues (BATs), which store and burn lipids, respectively, play critical roles in energy homeostasis. Fibroblast growth factors (FGFs) are signaling proteins with diverse functions in development, metabolism, and neural function. Among 22 FGFs, FGF1, FGF10, and FGF21 play roles as adipokines, adipocyte-secreted proteins, in the development and function of white and BATs. FGF1 is a critical transducer in white adipose tissue (WAT) remodeling. The peroxisome proliferator-activated receptor γ-FGF1 axis is critical for energy homeostasis. FGF10 is essential for embryonic white adipocyte development. FGF21 activates BAT in response to cold exposure. FGF21 also stimulates the accumulation of brown-like cells in WAT during cold exposure and is an upstream effector of adiponectin, which controls systemic energy metabolism. These findings provide new insights into the roles of FGF signaling in white and BATs and potential therapeutic strategies for metabolic disorders.
Differential Expression of the Urokinase Receptor in Fibroblasts from Normal and Fibrotic Human Lungs (1996)

Binding of urokinase-type plasminogen activator (uPA) to a specific receptor (uPAR) on human lung fibroblasts enables it to regulate cellular proteolysis and remodeling of the extracellular matrix. Binding studies with radiolabeled uPA indicated that both normal and fibrotic lung fibroblasts express the receptor, but cells from fibrotic tissues bound significantly more uPA (P < 0.001). Phorbol myristate acetate, lipopolysaccharide, transforming growth factor-beta (TGF-beta), and tumor necrosis factor-alpha (TNF-alpha) increased uPA binding and plasminogen activation at the cell surface, with a greater maximal effect on fibrotic than on normal fibroblasts. Excess unlabeled uPA, specific antibody, or antisense oligonucleotides inhibited uPA binding. Ribonuclease (RNase) protection assays showed higher levels of uPAR messenger ribonuleic acid (mRNA) in each of the five fibrotic cell lines than in normal fibroblasts. uPA was mitogenic for normal as well as fibrotic fibroblasts, indicating that receptor binding concurrently localizes cellular proteolytic activity and stimulates mitogenesis. Morphometry and immunohistochemical analysis showed that uPAR, as well as uPA, was increased in fibroblasts in fibrotic lung tissue. Increased expression of uPAR by fibrotic lung fibroblasts and enhanced urokinase binding induced by proinflammatory cytokines suggest a novel mechanism by which fibroblast-mediated matrix remodeling and proliferation may be regulated in interstitial lung diseases.
Structure-function studies of arginine at position 276 in CTX-M -lactamases (2008)

Arg-276 in CTX-M-type beta-lactamases is not equivalent to Arg-244 in IRT-type enzymes. Position Arg-276 appears to be important for cefotaxime hydrolysis in CTX-M-type enzymes, although different effects were obtained regarding the replaced amino acid.
Treatment of Generalized Hyperhidrosis with Oxybutynin in Postmenopausal Patients (2010)

Postmenopausal hyperhidrosis is a form of secondary hyperhidrosis, and hormone-replacement therapy is a commonly used therapeutic option. However, some women do not benefit from this treatment, and oral anticholinergics are a logical alternative for reducing generalized sweating in these patients. Twenty-one patients were medicated with 5 or 10 mg of oxybutynin per day. After a 3-month follow-up period, efficacy was assessed with the Hyperhidrosis Disease Severity Scale (HDSS) and the Dermatology Life Quality Index (DLQI) was used to assess the improvement in patients' quality of life. The HDSS score was 3.2 +/- 0.4 (mean +/- SD) before medication and 1.9 +/- 0.4 after 3 months. The baseline DLQI score of 8.4 +/- 1.0 was reduced to 4.4 +/- 0.9. No serious side-effects or adverse events resulted from treatment. Oxybutynin was a well-tolerated, effective, and safe method for treating postmenopausal sweating. However, long-term medication and the limited effects of the treatment were disadvantages.
Nanoscale Ion Beam Sculpting (2001)

meters is animportant scientific endeavor from which many future electronic, chemical andbiological advances are anticipated. We report on a method to fashionmaterials with nanoscale dimensions that is based on a new use of low energyion beams. The method is applied to the problem of fabricating a molecularscale hole, or nanopore, in a thin insulating solid-state membrane. Wedemonstrate that this new approach enables nanometer control of structuraldimensions and simultaneously provides a new tool for studying ion inducedmaterials phenomena on this length scale. We refer to the methodology asion beam sculpting and present data and a physical model explaining thefundamental mechanisms that are involved. We conclude with ademonstration of a nanoscale device fashioned by the method: a moleculedetector consisting of a single solid-state nanopore.
Specific Correction of Alternative Survival Motor Neuron 2 Splicing by Small Molecules: Discovery of a Potential Novel Medicine To Treat Spinal Muscular Atrophy (2016)

Spinal muscular atrophy (SMA) is the leading genetic cause of infant and toddler mortality, and there is currently no approved therapy available. SMA is caused by mutation or deletion of the survival motor neuron 1 (SMN1) gene. These mutations or deletions result in low levels of functional SMN protein. SMN2, a paralogous gene to SMN1, undergoes alternative splicing and exclusion of exon 7, producing an unstable, truncated SMNΔ7 protein. Herein, we report the identification of a pyridopyrimidinone series of small molecules that modify the alternative splicing of SMN2, increasing the production of full-length SMN2 mRNA. Upon oral administration of our small molecules, the levels of full-length SMN protein were restored in two mouse models of SMA. In-depth lead optimization in the pyridopyrimidinone series culminated in the selection of compound 3 (RG7800), the first small molecule SMN2 splicing modifier to enter human clinical trials.
Image capture and automatic identification of vehicle registration plates (1995)

This paper provides a summary of the work we have undertaken to date in the application of automatic number plate reading using image recognition techniques. It will chart progress from the early site trials to the latest application involving the production of a full violation record, its transmission to a remote centre and interface to an established account management facility able to process high volumes of violation records. (4 pages)
Phase I Cancer Clinical Trials: A Practical Guide (2006)

1. Introduction 2. Preclinical data and requirements 3. Basics of Phase I Design: first-in-man studies 4. Ethical issues in Phase I Cancer Trials 5. Phase I Trials in special populations 6. Statistical designs for Phase I Trials 7. Writing the protocol 8. Before you begin 9. Practical aspects of pharmacokinetics and pharmacodynamics 10. Running the study 11. Reporting and interpreting results Appendices
One-Step Synthesis of Silver Nanoparticles, Nanorods, and Nanowires on the Surface of DNA Network (2005)

Here, we describe a one-step synthesis of silver nanoparticles, nanorods, and nanowires on DNA network surface in the absence of surfactant. Silver ions were first adsorbed onto the DNA network and then reduced in sodium borohydride solution. Silver nanoparticles, nanorods, and nanowires were formed by controlling the size of pores of the DNA network. The diameter of the silver nanoparticles and the aspect ratio of the silver nanorods and nanowires can be controlled by adjusting the DNA concentration and reduction time.
Enhanced long-term predictor for Unified Speech and Audio Coding (2011)

Unified Speech and Audio Coding (USAC) is an emerging MPEG audio standard striving for efficiently representing both speech and music signals even in very low bitrate ranges. The reference codec takes an approach of unifying two state-of-the-art speech and audio coding structures in a single platform. This paper proposes an enhanced long term predictor (eLTP) that effectively utilizes periodic redundancies of inter- and intra- time frames. Experimental results with various types of input signals confirm the superiority of the proposed algorithm compared to the reference codec.
Polyurethane Ionomers, a New Class of Block Polymers (1970)

Abstract Linear polyurethanes containing ionic centers at wide intervals are heteropolymers having a pronounced segment structure, i.e. ionomers. As a result of interactions between chains (Coulomb forces and hydrogen bonds), their properties are similar to those of crosslinked elastomers. They are strongly associated both in organic and in aqueous solutions. Polyurethane ionomers in polar organic solvents spontaneously form stable aqueous dispersions on addition of water, with the ionomer as the disperse phase. The particle size can be varied between 20 nm and 1 mm.
Fetal valproate syndrome and autism: additional evidence of an association (2001)

Autism has been described in association with a variety of medical and genetic conditions. We previously reported on a patient whose clinical phenotype was compatible with both fetal valproate syndrome (FVS) and autism. Here we present five additional patients with FVS and autism. In all five of our patients, there was evidence of cognitive deficits, manifestations of autism, and typical phenotypic characteristics of FVS. The association between this known teratogen and autism has both clinical and research implications.
Sickle Cell Anemia: Targeting the Role of Fetal Hemoglobin in Therapy (2007)

Sickle cell anemia results from the single amino acid substitution of valine for glutamic acid in the beta-chain owing to a nucleotide defect that causes the production of abnormal beta-chains in hemoglobin S. Abnormal hemoglobin chains form polymers in the deoxygenated state, leading to the characteristic sickle cells. The polymerization of deoxygenated hemoglobin S accounts for the pathologic changes in sickle cell disease. The main-stay of therapy in sickle cell disease aims to reduce the amount of sickled hemoglobin present through the prevention of polymerization and reversal of this process. One way of discouraging polymerization is to increase the level of fetal hemoglobin, which because of its high oxygen affinity, does not participate in the polymerization process. Fetal hemoglobin production may be induced pharmacologically or by the use of gene therapy and genetic engineering techniques.
Graph-Based Algorithms for Boolean Function Manipulation (1986)

In this paper we present a new data structure for representing Boolean functions and an associated set of manipulation algorithms. Functions are represented by directed, acyclic graphs in a manner similar to the representations introduced by Lee [1] and Akers [2], but with further restrictions on the ordering of decision variables in the graph. Although a function requires, in the worst case, a graph of size exponential in the number of arguments, many of the functions encountered in typical applications have a more reasonable representation. Our algorithms have time complexity proportional to the sizes of the graphs being operated on, and hence are quite efficient as long as the graphs do not grow too large. We present experimental results from applying these algorithms to problems in logic design verification that demonstrate the practicality of our approach.
The Product of the HO Gene Is a Nuclease: Purification and Characterization of the Enzyme (1984)

Haploid cells of the yeast Saccharomyces cerevisiae exist as either of two mating types, a or α (Lindegren and Lindegren 1943). The two mating types are determined by two alleles of a single genetic locus, MAT, which maps to chromosome III. Cells of opposite mating types can mate (fuse) to form a/α diploids, which differ from haploid cells in two respects: Diploids are incapable of mating with either a or α cells (Roman et al. 1955), and they are able to undergo meiosis and sporulation (Roman and Sands 1953).
An empirical analysis of web page revisitation (2005)

There is a surprising lack of empirical research into user interaction with the web. This paper reports the results of an analysis of four months of logged data describing web use. The results update and extend earlier studies carried out in 1994 and 1995. We found that web page revisitation is a much more prevalent activity than previously reported (approximately 80% of pages have been previously visited by the user), that most pages are visited for a surprisingly short period of time, and that users maintain large (and possibly overwhelming) bookmark collections.
Epidermal growth factor-activated calcium and potassium channels. (1991)

The earliest responses to activation of the epidermal growth factor (EGF) receptor include a transient increase in calcium influx and a transient membrane hyperpolarization. The underlying mechanisms are, however, not well understood as yet. In the present study, we have applied patch clamp recording in the cell-attached and the outside-out mode, and fluorimetric cytosolic Ca2+ determinations, to identify the nature of the ion channels involved, to characterize their properties at the level of single channels, and to unravel their mechanism of activation. We provide evidence that activation of the EGF receptor results initially in the activation of voltage-independent Ca2+ channels that can be defined as direct receptor-operated channels. This in turn causes the activation of Ca(2+)-dependent K+ channels, which results in a (delayed) membrane hyperpolarization and then leads to the activation of a second class of Ca2+ channels that are sensitive to hyperpolarization. An autocatalytic generation of further hyperpolarization and Ca2+ influx is the predicted outcome of this ionic cascade. Based on the observed inhibitory effects of protein kinase C activation on the activity of Ca(2+)-dependent K+ channels, we propose that protein kinase C is involved in the negative regulation of this cascade, which explains the transient nature of these responses.
Real-Time Multi-Directional Data Compression Of Full Motion Video (1988)

There are a number of applications that necessitate the transmission of real-time images over a narrow bandwidth channel. These applications must utilize effective data compression algorithms in order to achieve their goals. Scientists have struggled to make quality video images over narrow channels utilizing a number of techniques. Many approaches tend to dissect images, exploiting both the temporal and spatial aspects of input sequences, and then to encode the transformed sections in a convenient and efficient approach. The Pyramid Algorithm performs spatial spectral decomposition so that high frequency information can be separated from its lower frequency components. This spatial pyramid transform is integrated into a system which utilizes both spatial and temporal correlation of real-time video sequences; the result is a robust system configuration that meets the required compression. The best acceptable image, given a specific data rate, is achieved by adaptively selecting either a spatial or a temporal algorithm on a pixel-by-pixel basis. Aspects of moving sequences can be classified so as to choose the best algorithm to minimize visible disturbances for that particular class.
Detergent-assisted oxidative folding of delta-conotoxins (2003)

Conotoxins comprise a diverse group of disulfide-rich peptides found in venoms of predatory Conus species. The native conformation of these peptides is marginally stable in comparison with alternative conformations, often resulting in low folding yields. The oxidative folding of hydrophobic delta-conotoxins was found to produce less than 1% of the native peptide [Bulaj, G. et al. (2001) Biochemistry 40, 13201]. In order to identify factors that might improve folding yields, we screened a number of additives including water-soluble polymers, detergents and osmolytes for their ability to increase steady-state accumulation of the native delta-conotoxin PVIA. The presence of a non-ionic detergent Tween and low temperature appeared to be the most effective factors in improving the oxidative folding. The detergent was also effective in promoting folding of other hydrophobic delta-conotoxins. Based on our findings, we discuss a possible mechanism for detergent-assisted folding and the general applicability of this mechanism to facilitating the proper folding of hydrophobic, cysteine-rich peptides.
Phenotypic Analysis of Antigen-Specific T Lymphocytes (1996)

Identification and characterization of antigen-specific T lymphocytes during the course of an immune response is tedious and indirect. To address this problem, the peptide-major histocompatability complex (MHC) ligand for a given population of T cells was multimerized to make soluble peptide-MHC tetramers. Tetramers of human lymphocyte antigen A2 that were complexed with two different human immunodeficiency virus (HIV)-derived peptides or with a peptide derived from influenza A matrix protein bound to peptide-specific cytotoxic T cells in vitro and to T cells from the blood of HIV-infected individuals. In general, tetramer binding correlated well with cytotoxicity assays. This approach should be useful in the analysis of T cells specific for infectious agents, tumors, and autoantigens.
Origin of the nonexponential thermal emission kinetics of D X centers in GaAlAs (1986)

Direct evidence has been found, via hydrostatic pressure experiments, that the random distribution of Al and Ga atoms (alloy broadening) is the main cause of the nonexponential behavior of thermal emission processes from DX centers in Ga1−xAlxAs alloys (0.19≤x≤0.74). Isothermal single-shot emission transients at constant capacitance were used to measure the nonexponential behavior. Experimental values of the degree of nonexponentiality at ambient pressure, as a function of the Al content, are in good agreement with an alloy broadening model. When hydrostatic pressure up to 11 kbar is applied, the nonexponential behavior does not change, confirming its independence from variations in the conduction-band structure.
Raised maternal serum placenta growth factor concentration during the second trimester is associated with Down syndrome (2002)

Maternal serum placenta growth factor concentration was elevated in Down syndrome pregnancies during the early second trimester. Placenta growth factor might be a novel marker for maternal serum Down syndrome screening.