gebhart/patrepeval huggingface dataset:
Measures for Corpus Similarity and Homogeneity (1998)

How similar are two corpora? A measure of corpus similarity would be very useful for NLP for many purposes, such as estimating the work involved in porting a system from one domain to another. First, we discuss difficulties in identifying what we mean by &amp;apos;corpus similariti: human similarity judgements are not finegrained enough, corpus similarity is inherently multidimensional, and similarity can only be interpreted in the light of corpus homogeneity. We then present an operational definition of corpus similarity \\vhich addresses or circumvents the problems, using purpose-built sets of aknown-similarity corpora&amp;quot;. These KSC sets can be used to evaluate the measures. We evaluate the measures described in the literature, including three variants of the information theoretic measure &amp;apos;perplexity&amp;apos;. A x 2-based measure, using word frequencies, is shnwn to be the best of those tested. The Problem How similar arc two corpora? The question arises on many occasions. In NLP, many useful results can be generated from corpora, but when can the results developed using one corpus be applied to another? How much will it cost to port an NLP application from one domain, with one corpus, to another, with another? For linguistics, does it matter whether language researchers use this corpora or that, or are they similar enough for it to mal&amp;lt;e no difference? There are also questions of more general interest. Looking at British national newspapers: is the Independent more like the Guardian or the Telegraph?&amp;apos; What are the constraints on a measure for corpus similarity? The first is simply that its findings correspond to unequivocal human judgements. It must
Nano-Welding by Scanning Probe Microscope (2005)

A novel method, nano-welding, analogous to spot welding at the nanoscale level using scanning probe microscopy (SPM) is presented. Using SPM oxidation of the underlying silicon, single-walled carbon nanotubes (SWNTs) have been immobilized to the surface at point sites along their lengths by the nano-welding. It is shown that this nano-welding process nearly has no structural damage to the SWNTs. This immobilization makes the SPM manipulation of SWNTs controllable and desirable, which is helpful for the construction of SWNT-based nanodevices.
Three phase emulsions for controlled delivery in the cosmetic field (1992)

Synopsis Adding perfluoropolymethylisopropylether (Fomblin HC) to conventional cosmetic emulsion, causes the physicochemical and applicative properties of the formulation to be deeply modified, the main feature being the formation of three phase systems. The in vitro effects on percutaneous absorption of adding Fomblin HC to a cosmetic emulsion of three model compounds was assessed using caffeine, testosterone and tritiated water as model compounds. In vitro experiments were carried out through human skin using static and flow-through diffusion cells. The presence of Fomblin HC (1, 3, 5%) in the emulsion decreased the percutaneous absorption of testosterone (0.01%) but increased water permeation. These effects were dependent on Fomblin HC concentration. On the contrary, caffeine flux through the skin was not affected by Fomblin addition to the emulsion.
l-Cysteine, a Versatile Source of Sulfenic Acids. Synthesis of Enantiopure Alliin Analogues (2004)

[reaction: see text] l-Cysteine is a stimulating starting product for the generation of transient sulfenic acids, such as 4, 6, 9, and 15, which add to suitable acceptors, allowing formation of sulfoxides showing a biologically active residue. These sulfoxides are easily isolated in enantiomerically pure form. For instance, N-(tert-butoxycarbonyl)-l-cysteine methyl ester (1a) furnished in few steps sulfenic acid 9a, which was readily converted into (R,S(S))-(2-tert-butoxycarbonylamino-2-methoxycarbonyl-ethylsulfinyl)ethene (22), the methyl ester of Boc-protected nor-alliin. Moreover, the addition of 9a to 2-methyl-1-buten-3-yne has led to a sulfur epimeric and separable mixture of (R)-2-(2-tert-butoxycarbonylamino-2-methoxycarbonyl-ethylsulfinyl)-3-methyl-buta-1,3-dienes 10a and 11a, still possessing a "masked" sulfenic acid function, producible from their cysteine moieties once the dienes have been converted into the desired derivatives.
Enhancing the genome editing toolbox: genome wide CRISPR arrayed libraries (2017)

CRISPR-Cas9 technology has accelerated biological research becoming routine for many laboratories. It is rapidly replacing conventional gene editing techniques and has high utility for both genome-wide and gene-focussed applications. Here we present the first individually cloned CRISPR-Cas9 genome wide arrayed sgRNA libraries covering 17,166 human and 20,430 mouse genes at a complexity of 34,332 sgRNAs for human and 40,860 sgRNAs for the mouse genome. For flexibility in generating stable cell lines the sgRNAs have been cloned in a lentivirus backbone containing PiggyBac transposase recognition elements together with fluorescent and drug selection markers. Over 95% of tested sgRNA induced specific DNA cleavage as measured by CEL-1 assays. Furthermore, sgRNA targeting GPI anchor protein pathway genes induced loss of function mutations in human and mouse cell lines measured by FLAER labelling. These arrayed libraries offer the prospect for performing screens on individual genes, combinations as well as larger gene sets. They also facilitate rapid deconvolution of signals from genome-wide screens. This set of vectors provide an organized comprehensive gene editing toolbox of considerable scientific value.
Columbia Classification Algorithm of Suicide Assessment (C-CASA): Classification of Suicidal Events in the FDA’s Pediatric Suicidal Risk Analysis of Antidepressants (2007)

Objective: To evaluate the link between antidepressants and suicidal behavior and ideation (suicidality) in youth, adverse events from pediatric clinical trials were classified in order to identify suicidal events. The authors describe the Columbia Classification Algorithm for Suicide Assessment (C-CASA), a standardized suicidal rating system that provided data for the pediatric suicidal risk analysis of antidepressants conducted by the Food and Drug Administration (FDA). Method: Adverse events (N=427) from 25 pediatric antidepressant clinical trials were systematically identified by pharmaceutical companies. Randomly assigned adverse events were evaluated by three of nine independent expert suicidologists using the Columbia classification algorithm. Reliability of the C-CASA ratings and agreement with pharmaceutical company classification were estimated. Results: Twenty-six new, possibly suicidal events (behavior and ideation) that were not originally identified by pharmaceutical companies were identified in the C-CASA, and 12 events originally labeled as suicidal by pharmaceutical companies were eliminated, which resulted in a total of 38 discrepant ratings. For the specific label of “suicide attempt,” a relatively low level of agreement was observed between the C-CASA and pharmaceutical company ratings, with the C-CASA reporting a 50% reduction in ratings. Thus, although the C-CASA resulted in the identification of more suicidal events overall, fewer events were classified as suicide attempts. Additionally, the C-CASA ratings were highly reliable (intraclass correlation coefficient [ICC]=0.89). Conclusions: Utilizing a methodical, anchored approach to categorizing suicidality provides an accurate and comprehensive identification of suicidal events. The FDA’s audit of the C-CASA demonstrated excellent transportability of this approach. The Columbia algorithm was used to classify suicidal adverse events in the recent FDA adult antidepressant safety analyses and has also been mandated to be applied to all anticonvulsant trials and other centrally acting agents and nonpsychotropic drugs.
Matrix Proteins and Mineralization: An Overview (1996)

There is a wealth of information on the mineral and matrix components in bones and teeth, in the exoskeletons of invertebrates, and in dystrophic calcific deposits. This information includes detailed characterization of their physical and chemical composition and details on the gene localization and regulation of gene expression for the major and minor protein constituents. The reason that mineral deposition occurs in some tissues and not in others remains unclear. In this review, studies in solution, cell culture studies, and investigations in mutant animals will be surveyed to indicate which matrix proteins may affect mineralization. Most of the molecules that appear to be involved in initiation and regulation of biological mineral formation are anionic; they have structural features that facilitate interaction with mineral, cells, and other matrix molecules, and they can have more than one function. Despite extensive data it is not yet clear which of these molecules is absolutely essential for physiologic calcification in each of the calcified tissues.
Adrenodoxin Reductase Homolog (Arh1p) of Yeast Mitochondria Required for Iron Homeostasis (2001)

Arh1p is an essential mitochondrial protein of yeast with reductase activity. Here we show that this protein is involved in iron metabolism. A yeast strain was constructed in which the open reading frame was placed under the control of a galactose-regulated promoter. Protein expression was induced by galactose and repressed to undetectable levels in the absence of galactose, although cells grew quite well in the absence of inducer. Under noninducing conditions, cellular iron uptake was dysregulated, exhibiting a failure to repress in response to medium iron. Iron trafficking within the cell was also disturbed. Exposure of Arh1p-depleted cells to increasing iron concentrations during growth led to drastic increases in mitochondrial iron, indicating a loss of homeostatic control. Activity of aconitase, a prototype Fe-S protein, was deficient at all concentrations of mitochondrial iron, although the protein level was unaltered. Heme protein deficiencies were exacerbated in the iron-loaded mitochondria, suggesting a toxic side effect of accumulated iron. Finally, a time course correlated the cellular depletion of Arh1p with the coordinated appearance of various mutant phenotypes including dysregulated cellular iron uptake, deficiency of Fe-S protein activities in mitochondria and cytoplasm, and deficiency of hemoproteins. Thus, Arh1p is required for control of cellular and mitochondrial iron levels and for the activities of Fe-S cluster proteins.
Structural and Functional Basis of Resistance to Neuraminidase Inhibitors of Influenza B Viruses (2010)

We have identified a virus, B/Perth/211/2001, with a spontaneous mutation, D197E in the neuraminidase (NA), which confers cross-resistance to all NA inhibitors. We analyzed enzyme properties of the D197 and E197 NAs and compared these to a D197N NA, known to arise after oseltamivir treatment. Zanamivir and peramivir bound slowly to the wild type NA, but binding of oseltamivir was more rapid. The D197E/N mutations resulted in faster binding of all three inhibitors. Analysis of the crystal structures of D197 and E197 NAs with and without inhibitors showed that the D197E mutation compromised the interaction of neighboring R150 with the N-acetyl group, common to the substrate sialic acid and all NA inhibitors. Although rotation of the E275 in the NA active site occurs upon binding peramivir in both the D197 and E197 NAs, this does not occur upon binding oseltamivir in the E197 NA. Lack of the E275 rotation would also account for the loss of slow binding and the partial resistance of influenza B wild type NAs to oseltamivir.
Bacterial strain‐specific induction of Foxp3+ T regulatory cells is protective in murine allergy models (2010)

Bacterial strain-specific induction of Foxp3(+) T regulatory cells in vivo is associated with protection from respiratory and oral allergy.
Digital manipulatives (1998)

In many educational settings, manipulative materials (such as Cuisenaire Rods and Pattern Blocks) play an important role in children's learning, enabling children to explore mathematical and scientific concepts (such as number and shape) through direct manipulation of physical objects. Our group at de MJT Media Lab has developed a new generation of "digital manipulatives"-computationallyenhanced versions of traditional children's toys. These new manipulatives enable children to explore a new set of concepts (im particular, "systems concepts" such as feedback and emergence) that have previously been considered "too advanced" for children to learn. In this paper, we discuss four of our digital manipulatives-computationallyaugmented versions of blocks, beads, balls, and badges.
Protein kinase C substrate and inhibitor characteristics of peptides derived from the myristoylated alanine-rich C kinase substrate (MARCKS) protein phosphorylation site domain (1991)

The phosphorylation sites in the myristoylated alanine-rich C kinase substrate or MARCKS protein consist of four serines contained within a conserved, basic region of 25 amino acids, termed the phosphorylation site domain. A synthetic peptide comprising this domain was phosphorylated by both protein kinase C and its catalytic fragment with high affinity and apparent positive cooperativity. Tryptic phosphopeptides derived from the peptide appeared similar to phosphopeptides derived from the phosphorylated intact protein. The peptide was phosphorylated by cAMP- and cGMP-dependent protein kinases with markedly lower affinities. In peptides containing only one of the four serines, with the other three serines replaced by alanine, the affinities for protein kinase C ranged from 25 to 60 nM with Hill constants between 1.8 and 3.0. The potential pseudosubstrate peptide, in which all four serines were replaced by alanines, inhibited protein kinase C phosphorylation of histone or a peptide substrate with an IC50 of 100-200 nM with apparently non-competitive kinetics; it also inhibited the catalytic fragment of protein kinase C with a Ki of 20 nM, with kinetics of the mixed type. The peptide did not significantly inhibit the cAMP- and cGMP-dependent protein kinases. It inhibited Ca2+/calmodulin-dependent protein kinases I, II, and III by competing with the kinases for calmodulin. In addition, the peptide inhibited the Ca2+/calmodulin-independent activity of a proteolytic fragment of Ca2+/calmodulin protein kinase II, with an IC50 approximately 5 microM. Thus, the phosphorylation site domain peptide of the MARCKS protein is a high affinity substrate for protein kinase C in vitro; the cognate peptide containing no serines is a potent but not completely specific inhibitor of both protein kinase C and its catalytic fragment.
Fusogenic Alzheimer's peptide fragment Aβ (29–42) in interaction with lipid bilayers: Secondary structure, dynamics, and specific interaction with phosphatidyl ethanolamine polar heads as revealed by solid‐state NMR (2005)

The interaction of the native Alzheimer's peptide C-terminal fragment Abeta (29-42), and two mutants (G33A and G37A) with neutral lipid bilayers made of POPC and POPE in a 9:1 molar ratio was investigated by solid-state NMR. This fragment and the lipid composition were selected because they represent the minimum requirement for the fusogenic activity of the Alzheimer's peptide. The chemical shifts of alanine methyl isotropic carbon were determined by MAS NMR, and they clearly demonstrated that the major form of the peptide equilibrated in membrane is not in a helical conformation. (2)H NMR, performed with acyl chain deuterated POPC, demonstrated that there is no perturbation of the acyl chain's dynamics and of the lipid phase transition temperature. (2)H NMR, performed with alanine methyl-deuterated peptide demonstrated that the peptide itself has a limited mobility below and above the lipid phase transition temperature (molecular order parameter equal to 0.94). MAS (31)P NMR revealed a specific interaction with POPE polar head as seen by the enhancement of POPE phosphorus nuclei T(2) relaxation. All these results are in favor of a beta-sheet oligomeric association of the peptide at the bilayer interface, preferentially recruiting phosphatidyl ethanolamine polar heads.
Dynamic email organization via relevance categories (2003)

Many researchers have proposed classification systems that automatically classify email in order to reduce information overload. However, none of these systems are in use today. This paper examines some of the problems with classification technologies and proposes Relevance Categories as a method to avoid some of these problems. In particular, the dynamic nature of email categories, the cognitive overhead, required training categories, and the high costs of classification errors are hurdles for many classification algorithms. Relevance Categories avoid some of these problems through their simplicity; they are merely relevance-ranked lists of email messages that are similar to a set of query messages. by displaying messages as the result of a dynamic query in lieu of fixed categories, we hypothesize that users will be less sensitive to errors using the Relevance Categories scheme than to errors using a fixed categorization scheme. To study the effectiveness of the Relevance Categories concept, we devised a performance metric for relevance ranking and used it to test an inverted index implementation on the Reuter-21578 test collection. The promising test results indicate the need for further work.
Interleukin 1 alpha causes rapid activation of cytosolic phospholipase A2 by phosphorylation in rat mesangial cells. (1994)

We have shown previously that interleukin 1 (IL-1) stimulates eicosanoid production in glomerular mesangial cells (MC) by de novo synthesis of a 14-kD, group II phospholipase A2 (PLA2). IL-1-stimulated prostaglandin E2 synthesis precedes expression of this enzyme, suggesting that another PLA2 isoform must be more rapidly activated. In the presence but not absence of calcium inophore, [3H]arachidonate release is increased significantly as early as 5 min after addition of IL-1, and IL-1 concurrently stimulates a Ca(2+)-dependent phospholipase activity, which was characterized as the cytosolic form of PLA2 (cPLA2). IL-1 does not alter either cPLA2 mRNA expression or mass in serum-stimulated MC, suggesting that cPLA2 activity is increased by a posttranslational modification. IL-1 treatment for 30 min doubles 32P incorporation into immunoprecipitable cPLA2 protein, concordant with the increase in enzyme activity. Immunoblot analysis of extracts derived from IL-1-treated (30 min) cells demonstrates a decreased mobility of cPLA2, and treatment of MC lysates with acid phosphatase significantly reduces cytokine-activated cPLA2 activity, further indicating that IL-1 stimulates phosphorylation of the enzyme. IL-1 treatment (24 h) of serum-deprived MC doubled cPLA2 mRNA, protein, and activity. In summary, IL-1 increases cPLA2 activity in a biphasic, time-dependent manner both by posttranslational modification and de novo synthesis. We consider cPLA2 activation a key step in IL-1-stimulated synthesis of pro-inflammatory, lipid mediators, and an integral event in the phenotypic responses induced in target cells by this cytokine.
Autoantibody Epitope Spreading in the Pre-Clinical Phase Predicts Progression to Rheumatoid Arthritis (2012)

Rheumatoid arthritis (RA) is a prototypical autoimmune arthritis affecting nearly 1% of the world population and is a significant cause of worldwide disability. Though prior studies have demonstrated the appearance of RA-related autoantibodies years before the onset of clinical RA, the pattern of immunologic events preceding the development of RA remains unclear. To characterize the evolution of the autoantibody response in the preclinical phase of RA, we used a novel multiplex autoantigen array to evaluate development of the anti-citrullinated protein antibodies (ACPA) and to determine if epitope spread correlates with rise in serum cytokines and imminent onset of clinical RA. To do so, we utilized a cohort of 81 patients with clinical RA for whom stored serum was available from 1-12 years prior to disease onset. We evaluated the accumulation of ACPA subtypes over time and correlated this accumulation with elevations in serum cytokines. We then used logistic regression to identify a profile of biomarkers which predicts the imminent onset of clinical RA (defined as within 2 years of testing). We observed a time-dependent expansion of ACPA specificity with the number of ACPA subtypes. At the earliest timepoints, we found autoantibodies targeting several innate immune ligands including citrullinated histones, fibrinogen, and biglycan, thus providing insights into the earliest autoantigen targets and potential mechanisms underlying the onset and development of autoimmunity in RA. Additionally, expansion of the ACPA response strongly predicted elevations in many inflammatory cytokines including TNF-α, IL-6, IL-12p70, and IFN-γ. Thus, we observe that the preclinical phase of RA is characterized by an accumulation of multiple autoantibody specificities reflecting the process of epitope spread. Epitope expansion is closely correlated with the appearance of preclinical inflammation, and we identify a biomarker profile including autoantibodies and cytokines which predicts the imminent onset of clinical arthritis.
Immunoconjugates containing novel maytansinoids: promising anticancer drugs. (1992)

The potential of immunoconjugates of cytotoxic drugs for the treatment of cancer has not yet been realized owing to the difficulty of delivering therapeutic concentrations of these drugs to the target cells. In an effort to overcome this problem we have synthesized maytansinoids that have 100- to 1000-fold higher cytotoxic potency than clinically used anticancer drugs. These maytansinoids are linked to antibodies via disulfide bonds, which ensures the release of fully active drug inside the cells. The conjugates show high antigen-specific cytotoxicity for cultured human cancer cells (50% inhibiting concentration, 10 to 40 pM), low systemic toxicity in mice, and good pharmacokinetic behavior.
Mechanisms of Atrial Fibrillation (2003)

Mechanisms of Atrial Fibrillation. Based on experimental studies in the canine heart and an early computer model, atrial fibrillation (AF) has been thought to be due to multiple reentrant wavelets. However, subsequent studies in animal models are most consistent with a mechanism of AF due to a stable reentrant circuit of short cycle length or unstable reentrant circuits of short cycle length that drive the atria so fast that much or most of the atrial tissue manifests fibrillatory conduction. Limited mapping studies in patients during open heart surgery and during electrophysiologic studies using endocardial catheter electrodes also are most consistent with the concept of a driver, seemingly most often a focus in or near one or more of the pulmonary veins, precipitating and maintaining AF. However, a precise understanding of the mechanism(s) of AF in patients is not yet available.
Mifepristone, a Glucocorticoid Receptor Antagonist, Produces Clinical and Metabolic Benefits in Patients with Cushing's Syndrome (2012)

Mifepristone produced significant clinical and metabolic improvement in patients with CS with an acceptable risk-benefit profile during 6 months of treatment.