gebhart/patrepeval huggingface dataset:
Lessons from the lysozyme of phage T4 (2010)

An overview is presented of some of the major insights that have come from studies of the structure, stability, and folding of T4 phage lysozyme. A major purpose of this review is to provide the reader with a complete tabulation of all of the variants that have been characterized, including melting temperatures, crystallographic data, Protein Data Bank access codes, and references to the original literature. The greatest increase in melting temperature (T(m)) for any point mutant is 5.1 degrees C for the mutant Ser 117 --> Val. This is achieved in part not only by hydrophobic stabilization but also by eliminating an unusually short hydrogen bond of 2.48 A that apparently has an unfavorable van der Waals contact. Increases in T(m) of more than 3-4 degrees C for point mutants are rare, whereas several different types of destabilizing substitutions decrease T(m) by 20 degrees C or thereabouts. The energetic cost of cavity creation and its relation to the hydrophobic effect, derived from early studies of "large-to-small" mutants in the core of T4 lysozyme, has recently been strongly supported by related studies of the intrinsic membrane protein bacteriorhodopsin. The L99A cavity in the C-terminal domain of the protein, which readily binds benzene and many other ligands, has been the subject of extensive study. Crystallographic evidence, together with recent NMR analysis, suggest that these ligands are admitted by a conformational change involving Helix F and its neighbors. A total of 43 nonisomorphous crystal forms of different monomeric lysozyme mutants were obtained plus three more for synthetically-engineered dimers. Among the 43 space groups, P2(1)2(1)2(1) and P2(1) were observed most frequently, consistent with the prediction of Wukovitz and Yeates.
Filgrastim (r-metHuG-CSF): the first 10 years (1996)

T HAS BEEN KNOWN for at least three decades that very specific factors control hematopoiesis, acting on early cells in the hematopoietic system to produce mature, functional cells. The isolation, purification, and cloning of these factors has lead to a new class of therapeutic agents, including the colony-stimulating factors and interleukins. This review is devoted to granulocyte colony-stimulating factor (G-CSF), specifically Filgrastim (r-metHuG-CSF), the bacterially synthesized recombinant protein form of GCSF, that acts on neutrophils, the body's major defense against infections. The purification and molecular cloning of Filgrastim were performed between 1984 and 1986,L-3 and the clinical development of Filgrastim commenced in 1986, with approval for clinical use in cancer patients treated with chemotherapy4 obtained in the United States in February 1991. In the 5 years since its approval, 1.2 million patients have been treated with Filgrastim (Amgen [Thousand Oaks, CA], data on file). Filgrastim was initially used as an adjunct to chemotherapy for ameliorating neutropenia, one of the major side effects of cancer chemotherapy. Its use has led to reduced infections and hospital admissions for patients with cancer. Besides chemotherapy-induced neutropenia, Filgrastim has been approved in more than 70 countries for the treatment of myelosuppression after bone marrow transplantation, severe chronic neutropenia (SCN), acute leukemia, aplastic anemia (AA), myelodysplastic syndromes (MDS), and mobilization of peripheral blood progenitor cells (PBPCs) for transplantation. The use of Filgrastim has made possible delivery of full-dose chemotherapy and high-dose chemotherapy and has benefited patients who are immunocompromised. A second form of rHuG-CSF (lenograstim) received approval in Europe in 1993. The biologic properties of Filgrastim and lenograstim are similar and are given in Table 1. This review focuses on Filgrastim and reviews the first 10 years of clinical development and the first 5 years of postapproval use as well as additional potential clinical applications. PHARMACOLOGY OF FlLGRASTlM The pharmacodynamics and pharmacokinetics of Filgrastim were studied in rodents',' and primates. and then in normal volunteers and in patients with malignant disease. The results of these studies indicated that Filgrastim had a consistent and predictable pharmacologic profile when ad
Characterization of a core α1→3‐fucosyltransferase from the snail Lymnaea stagnalis that is involved in the synthesis of complex‐type N‐glycans (1999)

We have identified a core alpha1-->3-fucosyltransferase activity in the albumin and prostate glands of the snail Lymnaea stagnalis. Incubation of albumin gland extracts with GDP-[(14)C]Fuc and asialo/agalacto-glycopeptides from human fibrinogen resulted in a labeled product in 50% yield. Analysis of the product by 400 MHz (1)H-NMR spectroscopy showed the presence of a Fuc residue alpha1-->3-linked to the Asn-linked GlcNAc. Therefore, the enzyme can be identified as a GDP-Fuc:GlcNAc (Asn-linked) alpha1-->3-fucosyltransferase. The enzyme acts efficiently on asialo/agalacto-glycopeptides from both human fibrinogen and core alpha1-->6-fucosylated human IgG, whereas bisected asialo/agalacto-glycopeptide could not serve as an acceptor. We propose that the enzyme functions in the synthesis of core alpha1-->3-fucosylated complex-type glycans in L. stagnalis. Core alpha1-->3-fucosylation of the asparagine-linked GlcNAc of plant- and insect-derived glycoproteins is often associated with the allergenicity of such glycoproteins. Since allergic reactions have been reported after consumption of snails, the demonstration of core alpha1-->3-fucosylation in L. stagnalis may be clinically relevant.
Modular control of multiple pathways using engineered orthogonal T7 polymerases (2012)

Synthetic genetic sensors and circuits enable programmable control over the timing and conditions of gene expression. They are being increasingly incorporated into the control of complex, multigene pathways and cellular functions. Here, we propose a design strategy to genetically separate the sensing/circuitry functions from the pathway to be controlled. This separation is achieved by having the output of the circuit drive the expression of a polymerase, which then activates the pathway from polymerase-specific promoters. The sensors, circuits and polymerase are encoded together on a 'controller' plasmid. Variants of T7 RNA polymerase that reduce toxicity were constructed and used as scaffolds for the construction of four orthogonal polymerases identified via part mining that bind to unique promoter sequences. This set is highly orthogonal and induces cognate promoters by 8- to 75-fold more than off-target promoters. These orthogonal polymerases enable four independent channels linking the outputs of circuits to the control of different cellular functions. As a demonstration, we constructed a controller plasmid that integrates two inducible systems, implements an AND logic operation and toggles between metabolic pathways that change Escherichia coli green (deoxychromoviridans) and red (lycopene). The advantages of this organization are that (i) the regulation of the pathway can be changed simply by introducing a different controller plasmid, (ii) transcription is orthogonal to host machinery and (iii) the pathway genes are not transcribed in the absence of a controller and are thus more easily carried without invoking evolutionary pressure.
Inhibition of tumor angiogenesis mediated by cartilage. (1975)

Capillary proliferation induced by tumor is shown to be inhibited by neonatal scapular cartilage. Using the rabbit cornea as an assay, the cartilage implant decreased the rate of capillary growth, induced by tumor, by an average of 75%. Vascularization was prevented completely in 28% of tumors. The inhibitory effect of small cartilage implants operates over distances of up to 2.0 mm and displays a gradient from the cartilage source. The experiments suggest that the cartilage inhibitor does not antagonize tumor angiogenesis factor, but appears to inhibit capillary proliferation directly. The inhibitory material does not elicit an inflammatory response in either the rabbit cornea or in the chick chorioallantoic membrane. Thus with further purification, it may prove useful as a means of maintining tumor dormancy by "antiangiogenesis."
Compelling intelligent user interfaces---how much AI? (1997)

Article Compelling intelligent user interfaces—how much AI? Share on Authors: Larry Birnbaum ILS/Northwestern, 1890 Maple Avenue, Evanston IL ILS/Northwestern, 1890 Maple Avenue, Evanston ILView Profile , Eric Horvitz Microsoft Research, One Microsoft Way, Redmond WA Microsoft Research, One Microsoft Way, Redmond WAView Profile , David Kurlander Microsoft Research, One Microsoft Way, Redmond WA Microsoft Research, One Microsoft Way, Redmond WAView Profile , Henry Lieberman MIT Media Laboratory, 20 Ames Street, Cambridge MA MIT Media Laboratory, 20 Ames Street, Cambridge MAView Profile , Joe Marks MERL, 201 Broadway, Cambridge MA MERL, 201 Broadway, Cambridge MAView Profile , Steve Roth Robotics Institute, Carnegie Mellon University, Pittsburgh PA Robotics Institute, Carnegie Mellon University, Pittsburgh PAView Profile Authors Info & Claims IUI '97: Proceedings of the 2nd international conference on Intelligent user interfacesJanuary 1997 Pages 173–175https://doi.org/10.1145/238218.238319Online:06 January 1997Publication History 16citation637DownloadsMetricsTotal Citations16Total Downloads637Last 12 Months41Last 6 weeks3 Get Citation AlertsNew Citation Alert added!This alert has been successfully added and will be sent to:You will be notified whenever a record that you have chosen has been cited.To manage your alert preferences, click on the button below.Manage my AlertsNew Citation Alert!Please log in to your account Save to BinderSave to BinderCreate a New BinderNameCancelCreateExport CitationPublisher SiteGet Access
Room temperature lasing from InGaAs quantum dots (1996)

Alternating molecular beam epitaxy is used to form InGaAs quantum dots by utilising the two-dimensional to three-dimensional Stranski-Krastanow growth transition. The quantum dots are embedded in a separate confinement heterostructure to form laser diodes. Lasing is observed from excited states in the quantum dots from room temperature down to 80 K. Pronounced state-filling is observed in the quantum dot lasers at room temperature. As the temperature is decreased, the state-filling becomes less pronounced, which compensates for the bandgap increase and leads to lasers whose lasing wavelength is very weakly dependent on temperature.
Repetitive Strain Injury (2001)

Repetitive Strain Injury is a serious condition that is painful and often debilitating. Also known as Cumulative Trauma Disorder, RSI occurs from physical movements that are repeated with a high rate of frequency.
Hyperopt: A Python Library for Optimizing the Hyperparameters of Machine Learning Algorithms (2013)

Sequential model-based optimization (also known as Bayesian optimization) is one of the most efficient methods (per function evaluation) of function minimization. This efficiency makes it appropriate for optimizing the hyperparameters of machine learning algorithms that are slow to train. The Hyperopt library provides algorithms and parallelization infrastructure for performing hyperparameter optimization (model selection) in Python. This paper presents an introductory tutorial on the usage of the Hyperopt library, including the description of search spaces, minimization (in serial and parallel), and the analysis of the results collected in the course of minimization. The paper closes with some discussion of ongoing and future work.
Chimeric T-Cell Receptors for the Targeting of Cancer Cells (2003)

Genetic engineering of human T lymphocytes to express tumor antigen-specific chimeric immune receptors is an attractive means for providing large numbers of effector cells for adoptive immunotherapy. Major mechanisms of tumor escape from immune recognition are efficiently bypassed. Although adoptive transfer of chimeric receptor-expressing peripheral blood-derived T lymphocytes has produced some anti-tumor activity in mice, the first clinical studies have revealed a disappointing lack of correlation between in vitro cytotoxicity and therapeutic efficacy. The most pertinent issue is that chimeric T cells fail to expand and rapidly lose their function in vivo. Potential strategies to enhance the therapeutic value of chimeric receptor-modified cells by preventing their functional inactivation in vivo are currently being investigated.
Target Identification by Diazirine Photo‐Cross‐Linking and Click Chemistry (2009)

Target identification of biologically active small-molecules is often the rate-determining step in forward chemical genetics. Photo-affinity labeling (PAL) represents a useful biochemical strategy for target identification in complex protein mixtures. This unit describes the use of alkyl diazirine-based photo-affinity probes and Cu(I)-catalyzed click chemistry to covalently label and visualize the targets of biologically active small-molecules. A general method for affinity purification of probe-modified proteins, useful for identification of protein targets, is also described.
Epidemiology of Idiosyncratic Drug-Induced Liver Injury (2009)

Idiosyncratic drug-induced liver injury (DILI) is a significant health problem because of its unpredictable nature, poorly understood pathogenesis, and potential to cause fatal outcomes. It is also a significant hurdle for drug development and marketing of safe prescription medications. Idiosyncratic DILI is generally rare, but its occurrence is likely underappreciated due to the lack of active reporting or surveillance systems and substantial challenges involved in its recognition and diagnosis. Nonetheless, DILI is a common cause of potentially serious and fatal acute liver failure in both children and adults. Population-based studies that accurately estimate the incidence and full spectrum of DILI are limited. However, using a prospective, population-based French study with an annual estimated incidence of 13.9 +/- 2.4 DILI cases per 100,000 inhabitants, it has been extrapolated that nearly 44,000 individuals in the United States will suffer from DILI each year. Although increasing numbers of patients are also being seen with DILI due to herbal and dietary supplements, the epidemiology of this entity requires further investigation. In this article, the epidemiology of DILI, both in the general population and in potentially high-risk subgroups, is reviewed.
Catchment scale patterns of aquatic hyphomycetes. The role of physicochemical variables and substrate composition in structuring conidial communities (2003)

Spatial dynamics of aquatic hyphomycete species were studied in four streams of a catchment in Hungary. Conidial pools at 11 sites were sampled by membrane filtration of stream water. Spatial relationships of the studied stream sites based on conidial communities were demonstrated by minimum spanning tree analyses. Metric multidimensional scaling was used to represent the similarity structure of the sites based on different sets of data. The evaluation of the results by procrustes analyses suggested that the effect of abiotic variables and the substrate composition on the structure of hyphomycete communities were both important, but not to the same degree. Ordination based on abiotic habitat variables showed somewhat higher similarity to ordination based on the hyphomycetes data than to ordination based on leaf litter data. The relationships between environmental variables and aquatic hyphomycete species were analysed by canonical correspondence analysis. The results suggested that altitude, water hardness and conductivity were the major factors correlated with the distribution of individual species. An alternative sampling technique for analysis of leaf litter composition in streams is discussed.
Use of Non-crystallographic Symmetry in Protein Structure Refinement (1996)

Several methods to assess the (dis)similarity of protein structures objectively are described, some of which, when applied to non-crystallographically related protein models, are able to discriminate between significant differences and 'random noise'. Some of these methods have been used to investigate a sample of several hundred protein structures which have been solved by means of X-ray crystallography in order to investigate the extent to which non-crystallographically related protein models differ from one another. It is shown that the extent of such differences is largely dependent on the resolution of the data used for the determination and refinement of the structure and, measured by some statistics, even varies essentially linearly with the resolution. The implications of these findings for the strategies used to refine structures with non-crystallographic symmetry, in particular at low resolution, are discussed. Finally, two examples are given of recent structure determinations from this laboratory in which the presence (and employment) of non-crystallographic symmetry was crucial to the solution and refinement of the structure.
Signal processing on the focal plane array: an overview (2000)

Raytheon's Infrared Operations (RIO) has invented and developed a new class of focal plane arrays; the Adaptive IR Sensor (AIRS) and Thinfilm Analog Image Processor (TAIP). The AIRS FPA is based upon biologically inspired on-focal- plane circuitry, which adaptively removes detector and optic temperature drift and l/f induced fixed pattern noise. This third-generation multimode IRFPA, also called a Smart FPA, is a 256x256-array format capable of operation in four modes: 1) Direct Injection (DI), 2) Adaptive Non-uniformity Correction (NUC), 3) Motion/Edge Detection, and 4) Subframe Averaging. Also the 320x240 TAIP results have shown excellent image processing in the form of Spatial and Temporal processing.
Th17 cells in cancer: help or hindrance? (2011)

The role of CD4+ T helper (Th) 17 cells in malignancy is currently under debate. However, upon closer scrutiny, it becomes apparent that this discussion includes not only evaluations of Th17 cells but also IL-17+ cells from other immune populations, the cytokine interleukin (IL)-17 itself (both endogenous and exogenous) and IL-23. Further complicating the matter are occasionally conflicting results of studies in humans versus those in mice and contradictory data from immunocompetent versus immunodeficient mice. To better understand the role of Th17 cells in the tumor-bearing host, we focus first upon those studies investigating Th17 cells in patients and then those in mice, all the while keeping in mind that variables such as tumor-initiating agents, a pre-existing inflammatory environment and the immune competence of the host may have direct effects upon this T-cell subset. In this review, we will describe the phenotype of tumor-associated Th17 cells, review those studies that have examined the population directly, and finally, briefly discuss the studies involving Th17-associated signature cytokines.
The Nature of Neural Invasion by Pancreatic Cancer (2007)

Neural invasion is a common, but not a specific, feature of pancreatic cancer. Tumor cells in the perineural space grow in a continuous fashion and may be responsible for some cases of lymphatic spread.
YMDD motif in hepatitis B virus DNA polymerase influences on replication and lamivudine resistance: a study by in vitro full-length viral DNA transfection (1999)

Recently, lamivudine used to treat patients with hepatitis B virus (HBV) infection was revealed to have potent antiviral activity. However, HBV resistance to lamivudine has been reported and shown to have amino acid substitutions in the methionine residue of the conserved tyrosine (Y), methionine (M), aspartate (D), aspartate (D) motif of RNA-dependent DNA polymerase. To explore the consequences of substitutions in this motif (YMDD), we made 7 variants by substituting the methionine of the YMDD motif with isoleucine (I), valine (V), alanine (A), leucine (L), lysine (K), arginine (R), and threonine (T). Replication ability of these variants was evaluated by transfection into human hepatoma cells. Sensitivity to lamivudine was tested for replication-competent variants. Four variants with hydrophobic substitutions (I, V, A, and L) remained replication-competent, whereas 3 others with hydrophilic substitutions (K, R, and T) exhibited impaired replication. Of the 4 replication-competent variants, 2 (I and V) were resistant, and 2 (A and L) were sensitive to lamivudine. Because the polymerase and the surface gene overlap, the introduction of these mutations affected the secretion of hepatitis B surface antigen (HBsAg), namely 4 variants (I, V, L, and R) secreted HBsAg, whereas 3 variants (A, K, and T) did not. Our study elucidated that only one amino acid substitution in the YMDD motif was sufficient to cause lamivudine resistance in vitro. As a result of replication competence and lamivudine sensitivity, only viruses having YIDD or YVDD sequences may appear during treatment with lamivudine. This in vitro system could be used to study HBV mutations, replication competence, and their susceptibility to antivirals.
A new hemoglobin gene from soybean: a role for hemoglobin in all plants. (1996)

We have isolated a new hemoglobin gene from soybean. It is expressed in cotyledons, stems of seedlings, roots, young leaves, and in some cells in the nodules that are associated with the nitrogen-fixing Bradyrhizobium symbiont. This contrasts with the expression of the leghemoglobins, which are active only in the infected cells of the nodules. The deduced protein sequence of the new gene shows only 58% similarity to one of the soybean leghemoglobins, but 85-87% similarity to hemoglobins from the nonlegumes Parasponia, Casuarina, and barley. The pattern of expression and the gene sequence indicate that this new gene is a nonsymbiotic legume hemoglobin. The finding of this gene in legumes and similar genes in other species strengthens our previous suggestion that genomes of all plants contain hemoglobin genes. The specialized leghemoglobin gene family may have arisen from a preexisting nonsymbiotic hemoglobin by gene duplication.
Mechanism of the urokinase-catalyzed activation of human plasminogen. (1976)

When human plasminogen (Glu-Pga) is activated by urokinase in the presence of pancreatic trypsin inhibitor, the plasmin produced (Glu-Pma) exclusively contains a heavy chain (Glu-Ha) derived intact from the original NH2 terminus of Glu-Pga. Similar activations, utilizing a low molecular weight synthetic plasmin acylating agent, p-nitrophenyl-p-(pyridiniummethyl) benzoate, still result in a plasmin molecule with approximately 50% of the plasmin heavy chain containing the intact NH2 terminus of the original Glu-Pga. Activations performed at high levels of urokinase in the absence of any inhibitors initially produce Glu-Pma. However, the final stable plasmin, Lys-Pmb, which is obtained contains a heavy chain (Lys-Hb) which arises by plasminolysis of a small peptide from the NH2 terminus of Glu-Ha. Alternatively, Lys-Pmb can be formed in a separate series of reactions initially involving plasminolysis of Glu-Pga to yield Lys-Pgb. The peptide removed in this step is identical to the peptide removed in the Glu-Ha to Lys-Hb reaction. Next, urokinase catalyzes the conversion of Lys-Pgb to Lys-Pmb without further loss of peptide material. This latter pathway involving Lys-Pgb is probably the major pathway for human Lys-Pmb generation. These studies support a mechanism of activation of human plasminogen which involves at least two bond cleavages in Glu-Pga. However, these same studies strongly indicate that the Nh2-terminal peptide need not be released from Glu-Pga prior to plasmin formation. Further, we feel that plasmin and not urokinase catalyzes cleavage of the NH2-terminal peptide bond from Glu-Pga and the Glu-Ha heavy chain of Glu-Pma.