gebhart/patrepeval huggingface dataset:
Design of a switchable eliminase (2011)

The active sites of enzymes are lined with side chains whose dynamic, geometric, and chemical properties have been finely tuned relative to the corresponding residues in water. For example, the carboxylates of glutamate and aspartate are weakly basic in water but become strongly basic when dehydrated in enzymatic sites. The dehydration of the carboxylate, although intrinsically thermodynamically unfavorable, is achieved by harnessing the free energy of folding and substrate binding to reach the required basicity. Allosterically regulated enzymes additionally rely on the free energy of ligand binding to stabilize the protein in a catalytically competent state. We demonstrate the interplay of protein folding energetics and functional group tuning to convert calmodulin (CaM), a regulatory binding protein, into AlleyCat, an allosterically controlled eliminase. Upon binding Ca(II), native CaM opens a hydrophobic pocket on each of its domains. We computationally identified a mutant that ( i ) accommodates carboxylate as a general base within these pockets, ( ii ) interacts productively in the Michaelis complex with the substrate, and ( iii ) stabilizes the transition state for the reaction. Remarkably, a single mutation of an apolar residue at the bottom of an otherwise hydrophobic cavity confers catalytic activity on calmodulin. AlleyCat showed the expected pH-rate profile, and it was inactivated by mutation of its active site Glu to Gln. A variety of control mutants demonstrated the specificity of the design. The activity of this minimal 75-residue allosterically regulated catalyst is similar to that obtained using more elaborate computational approaches to redesign complex enzymes to catalyze the Kemp elimination reaction.
AutoCAD 2008 For Dummies (2005)

A gentle, humorous introduction to this fearsomely complex software that helps new users start creating 2D and 3D technical drawings right awayCovers the new features and enhancements in the latest AutoCAD version and provides coverage of AutoCAD LT, AutoCAD''s lower-cost siblingTopics covered include creating a basic layout, using AutoCAD DesignCenter, drawing and editing, working with dimensions, plotting, using blocks, adding text to drawings, and drawing on the InternetAutoCAD is the leading CAD software for architects, engineers, and draftspeople who need to create detailed 2D and 3D tech
A novel hard magnetic material for sintering permanent magnets (1994)

We have discovered that the substitution of Ga or Si for Fe in Sm2Fe17Cx helps the formation of high-carbon rare-earth iron compounds with 2:17-type structure. We have succeeded in preparing Sm2Fe15M2Cx (M=Ga, x=0, 1.0, 2.0, and 3.0; M=Si, x=0, 0.5, 1.0, and 1.5) compounds with Th2Zn17-type structure by arc melting. The carbides are single phase except for Sm2Fe15Ga2C3.0, which contains a few percent of α-Fe. The Curie temperature TC of Sm2Fe15Si2Cx compounds is found to increase from 550 to 590 K, as x increases from 0 to 1.5. For Sm2Fe15Ga2Cx, TC increases with x from 565 K for x=0 to 635 K for x=2.0, and then decreases with x. Room-temperature saturation magnetization of these carbides is in excess of 100 emu/g and has a small dependence on carbon content. All compounds of Sm2Fe15M2Cx studied in this work except for Sm2Fe15Si2 exhibit an easy c-axis anisotropy at room temperature and show an anisotropy field of higher than 90 kOe for x≥1.0. The present work suggests the possibility of producing high-performance 2:17-type sintering permanent magnets.
Synthesis of Benzimidazole Ketene<b><i>N</i></b>,<b><i>S</i></b>-Acetals and Their Reactions with Nucleophiles (2003)

Abstract The novel ketene thioacetal 4 and ketene N,S-acetal 5 were readily prepared by the reaction of 2-cyanomethylbenzimidazole with either carbon disulfide or phenyl isothiocyanate in the presence of a base, followed by alkylation of the produced salts with methyl iodide. The reaction of compounds 4 and 5 with hydrazines afforded different benzimidazolyl substituted pyrazoles.
Interleukin 13 Mediates Signal Transduction through Interleukin 13 Receptor α2 in Pancreatic Ductal Adenocarcinoma: Role of IL-13 <i>Pseudomonas</i> Exotoxin in Pancreatic Cancer Therapy (2010)

These results indicate that IL-13Ralpha2 is a functional receptor as IL-13 mediates signaling in human pancreatic cancer cell lines. IL-13 causes transforming growth factor-beta activation via AP-1 pathway, which may cause tumor induced immunosuppression in the host. In addition, IL13-PE cytotoxin may be an effective therapeutic agent for the treatment of pancreatic cancer.
Guidelines on the Diagnosis and Management of Pericardial Diseases Executive SummaryThe Task Force on the Diagnosis and Management of Pericardial Diseases of the European Society of Cardiology (2004)

Guidelines and Expert Consensus documents aim to present all the relevant evidence on a particular issue in order to help physicians to weigh the benefits and risks of a particular diagnostic or therapeutic procedure.They should be helpful in everyday clinical decision-making.A great number of Guidelines and Expert Consensus Documents have been issued in recent years by different organisations, the European Society of Cardiology (ESC) and by other related societies.By means of links to web sites of National Societies several hundred guidelines are available.This profusion can put at stake the authority and validity of guidelines, which can only be guaranteed if they have been developed by an unquestionable decisionmaking process.This is one of the reasons why the ESC and others have issued recommendations for formulating and issuing Guidelines and Expert Consensus Documents.In spite of the fact that standards for issuing good quality Guidelines and Expert Consensus Documents are well defined, recent surveys of Guidelines and Expert Consensus Documents published in peer-reviewed journals between 1985 and 1998 have shown that methodological standards were not complied within the vast majority of cases.It is therefore of great importance that guidelines and recommendations are presented in formats that are easily interpreted.Subsequently, their implementation programmes must also be well conducted.Attempts have been made to determine whether guidelines improve the quality of clinical practice and the utilisation of health resources.The ESC Committee for Practice Guidelines (CPG) supervises and coordinates the preparation of new Guidelines and Expert Consensus Documents produced by Task Forces, expert groups or consensus panels.The Committee is also responsible for the endorsement of these Guidelines and Expert Consensus Documents or statements.
Exploration of the active center structure of nitrogen-doped graphene-based catalysts for oxygen reduction reaction (2012)

We present two different ways to fabricate nitrogen-doped graphene (N-graphene) and demonstrate its use as a metal-free catalyst to study the catalytic active center for the oxygen reduction reaction (ORR). N-graphene was produced by annealing of graphene oxide (G-O) under ammonia or by annealing of a N-containing polymer/reduced graphene oxide (RG-O) composite (polyaniline/RG-O or polypyrrole/RG-O). The effects of the N precursors and annealing temperature on the performance of the catalyst were investigated. The bonding state of the N atom was found to have a significant effect on the selectivity and catalytic activity for ORR. Annealing of G-O with ammonia preferentially formed graphitic N and pyridinic N centers, while annealing of polyaniline/RG-O and polypyrrole/RG-O tended to generate pyridinic and pyrrolic N moieties, respectively. Most importantly, the electrocatalytic activity of the catalyst was found to be dependent on the graphitic N content which determined the limiting current density, while the pyridinic N content improved the onset potential for ORR. However, the total N content in the graphene-based non-precious metal catalyst does not play an important role in the ORR process.
Evaluation of Physical Examination Tests for Thumb Basal Joint Osteoarthritis (2016)

The lever test was the diagnostic test that best reproduced the pain caused by thumb basal joint osteoarthritis. We recommend using the lever physical examination test when evaluating the patient with suspected basal joint osteoarthritis. The often-quoted grind test is of limited diagnostic value.
Nanoscale Metal–Organic Frameworks for Therapeutic, Imaging, and Sensing Applications (2018)

Nanotechnology has played an important role in drug delivery and biomedical imaging over the past two decades. In particular, nanoscale metal-organic frameworks (nMOFs) are emerging as an important class of biomedically relevant nanomaterials due to their high porosity, multifunctionality, and biocompatibility. The high porosity of nMOFs allows for the encapsulation of exceptionally high payloads of therapeutic and/or imaging cargoes while the building blocks-both ligands and the secondary building units (SBUs)-can be utilized to load drugs and/or imaging agents via covalent attachment. The ligands and SBUs of nMOFs can also be functionalized for surface passivation or active targeting at overexpressed biomarkers. The metal ions or metal clusters on nMOFs also render them viable candidates as contrast agents for magnetic resonance imaging, computed tomography, or other imaging modalities. This review article summarizes recent progress on nMOF designs and their exploration in biomedical areas. First, the therapeutic applications of nMOFs, based on four distinct drug loading strategies, are discussed, followed by a summary of nMOF designs for imaging and biosensing. The review is concluded by exploring the fundamental challenges facing nMOF-based therapeutic, imaging, and biosensing agents. This review hopefully can stimulate interdisciplinary research at the intersection of MOFs and biomedicine.
Repression of FLOWERING LOCUS T Chromatin by Functionally Redundant Histone H3 Lysine 4 Demethylases in Arabidopsis (2009)

FLOWERING LOCUS T (FT) plays a key role as a mobile floral induction signal that initiates the floral transition. Therefore, precise control of FT expression is critical for the reproductive success of flowering plants. Coexistence of bivalent histone H3 lysine 27 trimethylation (H3K27me3) and H3K4me3 marks at the FT locus and the role of H3K27me3 as a strong FT repression mechanism in Arabidopsis have been reported. However, the role of an active mark, H3K4me3, in FT regulation has not been addressed, nor have the components affecting this mark been identified. Mutations in Arabidopsis thaliana Jumonji4 (AtJmj4) and EARLY FLOWERING6 (ELF6), two Arabidopsis genes encoding Jumonji (Jmj) family proteins, caused FT-dependent, additive early flowering correlated with increased expression of FT mRNA and increased H3K4me3 levels within FT chromatin. Purified recombinant AtJmj4 protein possesses specific demethylase activity for mono-, di-, and trimethylated H3K4. Tagged AtJmj4 and ELF6 proteins associate directly with the FT transcription initiation region, a region where the H3K4me3 levels were increased most significantly in the mutants. Thus, our study demonstrates the roles of AtJmj4 and ELF6 as H3K4 demethylases directly repressing FT chromatin and preventing precocious flowering in Arabidopsis.
Privacy Preserving for Tagging Recommender Systems (2013)

Tagging recommender systems allow Internet users to annotate resources with personalized tags. The connection among users, resources and these annotations, often called afolksonomy, permits users the freedom to explore tags, and to obtain recommendations. Releasing these tagging datasets accelerates both commercial and research work on recommender systems. However, adversaries may re-identify a user and her/his sensitivity information from the tagging dataset using a little background information. Recently, several private techniques have been proposed to address the problem, but most of them lack a strict privacy notion, and can hardly resist the number of possible attacks. This paper proposes an private releasing algorithm to perturb users' profile in a strict privacy notion, differential privacy, with the goal of preserving a user's identity in a tagging dataset. The algorithm includes three privacy preserving operations: Private Tag Clustering is used to shrink the randomized domain and Private Tag Selection is then applied to find the most suitable replacement tags for the original tags. To hide the numbers of tags, the third operation, Weight Perturbation, finally adds Lap lace noise to the weight of tags We present extensive experimental results on two real world datasets, Delicious and Bibsonomy. While the personalization algorithmis successful in both cases.
Possible role for cell-surface carbohydrate-binding molecules in lymphocyte recirculation. (1983)

We are investigating the hypothesis that carbohydrate-binding molecules on the cell surface are involved in the recirculation of lymphocytes from the bloodstream into lymphoid organs. This phenomenon requires the specific attachment of circulating lymphocytes to the endothelial cells of postcapillary venules. Using an in vitro assay to measure the adhesive interaction between lymphocytes and postcapillary venules, we have found that L-fucose, D mannose, and the L-fucose-rich, sulfated polysaccharide fucoidin specifically inhibit this binding interaction. L-fucose shows stereo-selective inhibitory activity at concentrations greater than 18 mM while fucoidin produces 50% inhibition at approximately 1-5 X 10(-8) M. Fucoidin appears to interact with the lymphocyte, and not the postcapillary venule, to inhibit binding. These data suggest that cell surface carbohydrates (fucoselike) and carbohydrate-binding molecules (cell surface lectins) may contribute to the specific attachment of lymphocytes to postcapillary venules.
[Neurosurgical embryology. Part 1: Cell differentiation]. (2003)

In pluricellular organisms, cell differentiation helps to decrease the total amount of energy needed for life. These differentiations can be evidenced at the tissular, the cellular or the molecular levels. Cell differentiation is a progressive process achieved during embryogenesis; different steps in the program can be described. One of the explanations to account for cell differentiation is the specific expression of proteins, called transcription factors, that can control the expression of selected genes. These factors are classified according to their biochemical pattern allowing description of several families of transcription factors. One of the salient questions during embryogenesis is to understand the mechanisms involved in cell differentiation. The first event is due to asymmetry of mitosis leading to the generation of two cell lineages. This is favored by the initial ovocyte polarization. The second event is due to cell interactions (namely inductions). These inductions may be explained either by cell-cell contact (favored by cell adhesion molecules) or by secreting factors that can be either hydrophilic or lipophilic.
<i>In Vivo</i> Consequences of Putative Active Site Mutations in Yeast DNA Polymerases α, ε, δ, and ζ (2001)

Several amino acids in the active site of family A DNA polymerases contribute to accurate DNA synthesis. For two of these residues, family B DNA polymerases have conserved tyrosine residues in regions II and III that are suggested to have similar functions. Here we replaced each tyrosine with alanine in the catalytic subunits of yeast DNA polymerases alpha, delta, epsilon, and zeta and examined the consequences in vivo. Strains with the tyrosine substitution in the conserved SL/MYPS/N motif in region II in Pol delta or Pol epsilon are inviable. Strains with same substitution in Rev3, the catalytic subunit of Pol zeta, are nearly UV immutable, suggesting severe loss of function. A strain with this substitution in Pol alpha (pol1-Y869A) is viable, but it exhibits slow growth, sensitivity to hydroxyurea, and a spontaneous mutator phenotype for frameshifts and base substitutions. The pol1-Y869A/pol1-Y869A diploid exhibits aberrant growth. Thus, this tyrosine is critical for the function of all four eukaryotic family B DNA polymerases. Strains with a tyrosine substitution in the conserved NS/VxYG motif in region III in Pol alpha, -delta, or -epsilon are viable and a strain with the homologous substitution in Rev3 is UV mutable. The Pol alpha mutant has no obvious phenotype. The Pol epsilon (pol2-Y831A) mutant is slightly sensitive to hydroxyurea and is a semidominant mutator for spontaneous base substitutions and frameshifts. The Pol delta mutant (pol3-Y708A) grows slowly, is sensitive to hydroxyurea and methyl methanesulfonate, and is a strong base substitution and frameshift mutator. The pol3-Y708A/pol3-Y708A diploid grows slowly and aberrantly. Mutation rates in the Pol alpha, -delta, and -epsilon mutant strains are increased in a locus-specific manner by inactivation of PMS1-dependent DNA mismatch repair, suggesting that the mutator effects are due to reduced fidelity of chromosomal DNA replication. This could result directly from relaxed base selectivity of the mutant polymerases due to the amino acid changes in the polymerase active site. In addition, the alanine substitutions may impair catalytic function to allow a different polymerase to compete at the replication fork. This is supported by the observation that the pol3-Y708A mutation is recessive and its mutator effect is partially suppressed by disruption of the REV3 gene.
The Histopathology of Vulvar Vestibulitis Syndrome (1988)

Forty-one cases of vulvar vestibulitis syndrome are presented. All cases were studied to provide a histopathological description of this condition in terms of location, intensity, and characterization of the inflammatory response. Alterations of the normal histology of minor vestibular glands forming vestibular clefts are described. The association of this condition with other disease processes, and special studies done to elucidate an etiology, are discussed.
Frequency Doubling in Ferrites (1956)

The torque equation for the motion of the magnetization in a magnetized ferrite yields a component along the direction of the applied dc magnetic field. The time dependent part of this component is of second order in rf quantities and has previously been neglected. With high incident powers an observable double frequency output is predicted. A high intensity microwave magnetic field and an orthogonal dc magnetic field were applied to a ferrite body. Double frequency magnetic fields were generated in the same direction as the dc magnetizing field. A primary frequency of 3175 mc was used with peak powers up to 200 watts. The peak output power at 6350 mc was found to increase linearly with the square of the peak input power over a range of 42 db. Reasonable agreement was found between theory and experiment.
Birth of Cloned Calves Derived from Cultured Oviductal Epithelial Cells of a Dairy Cow (1999)

The present study aims to examine the effects of the use of two kinds of somatic cells from a single adult cow on fusion rate, cleavage rate, developmental rate into blastocysts of nuclear transplant oocytes, and pregnancy potential of reconstituted blastocysts. Oviductal epithelial cells and mammary gland cells from a single adult Jersey cow with a milking record were used in the present experiment. No significant differences were observed in the in vitro criteria described above between two cell types used as a source of donor nucleus. Although pregnancies were obtained from both cell types, live calves resulted only from embryos cloned from oviductal epithelial cells. Using oviductal epithelial cells, three out of ten recipients became pregnant. Two carried to full term and delivered one female calf each at day 285 of gestation. The birth weights of two live female calves were 27.5kg and 30.0kg. The third aborted at day 251 of gestation. On the other hand, using mammary gland cells, one out of six recipients became pregnant but aborted at day 81 of gestation. Genomic DNA analyses confirmed that the calves are all genetically identical to the nuclear donor cell.
Systemic Gene Transfer of a Hexosaminidase Variant Using an scAAV9.47 Vector Corrects G <sub>M2</sub> Gangliosidosis in Sandhoff Mice (2016)

GM2 gangliosidosis is a group of neurodegenerative diseases caused by β-hexosaminidase A (HexA) enzyme deficiency. There is currently no cure. HexA is composed of two similar, nonidentical subunits, α and β, which must interact with the GM2 activator protein (GM2AP), a substrate-specific cofactor, to hydrolyze GM2 ganglioside. Mutations in either subunit or the activator can result in the accumulation of GM2 ganglioside within neurons throughout the central nervous system. The resulting neuronal cell death induces the primary symptoms of the disease: motor impairment, seizures, and sensory impairments. This study assesses the long-term effects of gene transfer in a Sandhoff (β-subunit knockout) mouse model. The study utilized a modified human β-hexosaminidase α-subunit (μ-subunit) that contains critical sequences from the β-subunit that enables formation of a stable homodimer (HexM) and interaction with GM2AP to hydrolyze GM2 ganglioside. We investigated a self-complementary adeno-associated viral (scAAV) vector expressing HexM, through intravenous injections of the neonatal mice. We monitored one cohort for 8 weeks and another cohort long-term for survival benefit, behavioral, biochemical, and molecular analyses. Untreated Sandhoff disease (SD) control mice reached a humane endpoint at approximately 15 weeks, whereas treated mice had a median survival age of 40 weeks, an approximate 2.5-fold survival advantage. On behavioral tests, the treated mice outperformed their knockout age-matched controls and perform similarly to the heterozygous controls. Through the enzymatic and GM2 ganglioside analyses, we observed a significant decrease in the GM2 ganglioside level, even though the enzyme levels were not significantly increased. Molecular analyses revealed a global distribution of the vector between brain and spinal cord regions. In conclusion, the neonatal delivery of a novel viral vector expressing the human HexM enzyme is effective in ameliorating the SD mouse phenotype for long-term. Our data could have implications not only for treatment of SD but also for Tay-Sachs disease (α-subunit deficiency) and similar brain disorders.
Generic Modulation Adaptive LINC Transmitter (2002)

A novel generic LINC topology with multiple digital modulation capability is introduced. It uses two pairs of phase conjugated signals in quadrature to form any of the commonly used data communications modulation schemes, namely BPSK, QPSK, OQPSK, 8PSK, 16PSK, 8QAM, 16 QAM, etc. Due to the constant envelope of the composite signals forming each of the two signal pairs the requirements for linear amplification normally associated with these modulation schemes are removed, hence highly DC to RF efficient non-linear amplifiers can be used. In addition the system is shown to have natural harmonic suppression. Further, output power control, e.g. required for CDMA, can be executed without the need for amplifler level/bias control or attenuators.
Time-dependent learning (2004)

Traditional learning systems work offline. Their output acquired after some unknown long time delay is a comprehensive instruction. However, the utility of such knowledge reduces in a time-constrained environment where instruction has to be completed by a certain deadline. As learning material scale up and longer instruction times become common, knowledge acquisition become time-dependent and is increasingly acquired on the fly due to considerable changes in today's know-how economy requirements. In this paper, we propose a procedural tradeoff between the time allocated to an instruction and the quality of the corresponding knowledge volume.