gebhart/patrepeval huggingface dataset:
Ligand-Mediated Protection against Phage Lysis as a Positive Selection Strategy for the Enrichment of Epitopes Displayed on the Surface of E. coli Cells (2001)

We present a novel strategy, termed CISTEM, which allows direct in vivo screening of polypeptides displayed on the surface of E. coli cells by a combination of ligand-mediated protection and phage-mediated selection. The effectiveness of this new approach was demonstrated by displaying the T7.tag on the surface of E. coli as a fusion with the outer membrane protein A, the receptor for bacteriophage K3. A monoclonal T7.tag antibody was used as protective ligand for T7.tag-displaying cells and phage K3 for the elimination of unprotected cells. When populations of bacteria, containing between 6 to 10,000 cells displaying the T7.tag and approximately 10(8) cells displaying an unrelated OmpA fusion protein, were infected with phage K3, specific and antibody-dependent survival of T7.tag displaying cells was observed, yielding an enrichment factor of up to 10(7)-fold. The CISTEM technology was used to select sequences from a T7.tag-based, randomised library and the results were compared to those obtained from selection by MACS with the same library. Together, these results reveal a novel in vivo screening strategy in which an E. coli phage receptor is used as display plafform and selection is performed in suspension upon addition of a protective ligand and a bacteriophage. Extentions and modifications of the basic strategy should lead to novel applications for the identification of protein-ligand interactions.
Fine-grained Analysis of Sentence Embeddings Using Auxiliary Prediction Tasks (2016)

There is a lot of research interest in encoding variable length sentences into fixed length vectors, in a way that preserves the sentence meanings. Two common methods include representations based on averaging word vectors, and representations based on the hidden states of recurrent neural networks such as LSTMs. The sentence vectors are used as features for subsequent machine learning tasks or for pre-training in the context of deep learning. However, not much is known about the properties that are encoded in these sentence representations and about the language information they capture. We propose a framework that facilitates better understanding of the encoded representations. We define prediction tasks around isolated aspects of sentence structure (namely sentence length, word content, and word order), and score representations by the ability to train a classifier to solve each prediction task when using the representation as input. We demonstrate the potential contribution of the approach by analyzing different sentence representation mechanisms. The analysis sheds light on the relative strengths of different sentence embedding methods with respect to these low level prediction tasks, and on the effect of the encoded vector's dimensionality on the resulting representations.
Coacervate delivery of HB‐EGF accelerates healing of type 2 diabetic wounds (2015)

Chronic wounds such as diabetic ulcers pose a significant challenge as a number of underlying deficiencies prevent natural healing. In pursuit of a regenerative wound therapy, we developed a heparin-based coacervate delivery system that provides controlled release of heparin-binding epidermal growth factor (EGF)-like growth factor (HB-EGF) within the wound bed. In this study, we used a polygenic type 2 diabetic mouse model to evaluate the capacity of HB-EGF coacervate to overcome the deficiencies of diabetic wound healing. In full-thickness excisional wounds on NONcNZO10 diabetic mice, HB-EGF coacervate enhanced the proliferation and migration of epidermal keratinocytes, leading to accelerated epithelialization. Furthermore, increased collagen deposition within the wound bed led to faster wound contraction and greater wound vascularization. Additionally, in vitro assays demonstrated that HB-EGF released from the coacervate successfully increased migration of diabetic human keratinocytes. The multifunctional role of HB-EGF in the healing process and its enhanced efficacy when delivered by the coacervate make it a promising therapy for diabetic wounds.
Complete sequence of the human tissue factor gene, a highly regulated cellular receptor that initiates the coagulation protease cascade (1989)

Tissue factor (TF) is the high-affinity receptor for plasma factors VII and VIIa. TF plays a role in normal hemostasis by initiating the cell-surface assembly and propagation of the coagulation protease cascade. Outside the vasculature, TF expression is highly dependent upon cell type. TF can also be induced by inflammatory mediators to appear on monocytes and vascular endothelial cells as a component of cellular immune responses. As an initial step toward elucidating the regulatory regions involved in control of TF gene expression, we have established the organization of the 12.4 kbp human TF gene and its complete DNA sequence. There are six exons separated by five introns. Within intron 5, we have mapped the single nucleotide difference which leads to the previously described MspI polymorphism; the same intron also contains an apparently polymorphic PstI site. The TF gene also contains three full-length Alu repeats and one partial Alu repeat. A single major transcription start site was identified 26 bp downstream from a TATA consensus promoter element. The putative promoter and first exon are located within a 1.2 kbp region of very high G + C content which fits the criteria of an HTF island. A cluster of predicted binding sites for a number of known transcription factors was found to coincide with this putative promoter region. These factors included AP-1 and AP-2 which can mediate the effects of phorbol esters, agonists known to induce TF expression in monocytes and vascular endothelial cells.
Atrial natriuretic peptide(31-67) inhibits Na+ transport in rabbit inner medullary collecting duct cells. Role of prostaglandin E2. (1992)

Atrial natriuretic peptide (ANP)(31-67), a portion of the atrial peptide prohormone, circulates in humans, and its plasma level varies with atrial pressure. Like the more widely studied carboxy-terminal fragment ANP(99-126), ANP(31-67) stimulates natriuresis and diuresis. We examined the mechanism of this natriuresis by measuring the effects of ANP(31-67) on Na+ transport in cells of the rabbit inner medullary collecting duct (IMCD). ANP(31-67) (10(-8) M) caused a 26 +/- 4% inhibition of oxygen consumption (QO2); half-maximal inhibition occurred at 10(-11) M, suggesting a physiologic effect. This effect was not additive with either ouabain or amiloride, suggesting that it reflected inhibition of Na+ transport-dependent QO2. ANP(31-67) reduced the amphotericin-induced stimulation of QO2 consistent with inhibition by this peptide of the Na(+)-K(+)-ATPase. In addition, ANP(31-67) reduced ouabain-sensitive 86Rb+ uptake under Vmax conditions. Several lines of evidence indicated that PGE2, a known endogenous IMCD Na(+)-K(+)-ATPase inhibitor, mediates pump inhibition by ANP(31-67). Thus, ANP(31-67) inhibits Na+ transport by inhibiting the Na(+)-K(+)-ATPase of IMCD cells, an effect mediated by the generation of PGE2.
How Important are Models to Operational Research? (1989)

This paper starts from the assumption that the use of models is central to the methodology of operational research (OR). The concept is clarified by reference to its formal use in mathematical logic. A justification for the use of models in decision making is given. This is contrasted with the reasons why traditional OR models are frequently not used by practising OR workers (let alone managers). An attempt is made to resolve this contrast between the practice of OR by academics with those closer to commercial decision making. The proper relationship between the two activities is suggested.
Presenilin-1 binds cytoplasmic epithelial cadherin, inhibits cadherin/p120 association, and regulates stability and function of the cadherin/catenin adhesion complex (2001)

Here we show that presenilin-1 (PS1), a protein involved in Alzheimer's disease, binds directly to epithelial cadherin (E-cadherin). This binding is mediated by the large cytoplasmic loop of PS1 and requires the membrane-proximal cytoplasmic sequence 604-615 of mature E-cadherin. This sequence is also required for E-cadherin binding of protein p120, a known regulator of cadherin-mediated cell adhesion. Using wild-type and PS1 knockout cells, we found that increasing PS1 levels suppresses p120/E-cadherin binding, and increasing p120 levels suppresses PS1/E-cadherin binding. Thus PS1 and p120 bind to and mutually compete for cellular E-cadherin. Furthermore, PS1 stimulates E-cadherin binding to beta- and gamma-catenin, promotes cytoskeletal association of the cadherin/catenin complexes, and increases Ca(2+)-dependent cell-cell aggregation. Remarkably, PS1 familial Alzheimer disease mutant DeltaE9 increased neither the levels of cadherin/catenin complexes nor cell aggregation, suggesting that this familial Alzheimer disease mutation interferes with cadherin-based cell-cell adhesion. These data identify PS1 as an E-cadherin-binding protein and a regulator of E-cadherin function in vivo.
Activity‐Based Near‐Infrared Fluorescent Probe for LMP7: A Chemical Proteomics Tool for the Immunoproteasome in Living Cells (2012)

Probing the unknown: The immunoproteasome, an alternative form of the constitutive proteasome, has been implicated in a number of pathological states such as cancer and autoimmune diseases. In an effort to understand the role of the immunoproteasome in cells, the first immunoproteasome-specific near-infrared fluorescent probe has been developed.
Anxiolytic-like effect of trans-2-decenoic acid ethyl ester in stress-induced anxiety-like model mice (2013)

Brain-derived neurotrophic factor (BDNF) is considered to be involved in the etiology and treatment of stress-related mood disorders including anxiety. However, application of BDNF itself has many technical and pharmacological problems such as instability and/or a lack of appropriate delivery systems. To overcome these, we developed trans-2-decenoic acid ethyl ester (DAEE) as a stable and small molecule with BDNF-like activities. In the present study, we tested the activities of DAEE on a stress-induced anxiety-like mouse model. Mice were kept in cages and subjected to 3 sets of sequential leaning, drenching, and rotation as chronic mild stresses applied for 1-2 days over a 3-week period; and the anxiety-like symptom (reduced time spent in open arm of the maze) was evaluated by use of the elevated plus-maze test. A daily intraperitoneal administration of DAEE competed against the expression of the anxiety-like symptom when administered during the stress-loading period, and became therapeutic when administered after the stress-loading. This activity was accompanied by amelioration of the stress-induced reduction in the levels of BDNF and neurotrophin-3 mRNAs and phosphorylated extracellular signal-regulated kinases (ERK) 1/2 in the hippocampus. These results demonstrated that DAEE behaved like an anxiolytic and ameliorated this characteristic anxiety-like symptom, suggesting that DAEE may be a promising candidate for a novel anxiolytic with a new mechanism of action.
A stochastic model of superstardom: evidence from institutional investor's All‐American Research Team (2000)

Abstract In this paper, we investigate the superstar phenomenon in the security analysis industry through an analysis of the probabilistic mechanism by which security analysts are selected for inclusion in Institutional Investor 's All‐American Research Team (II AART). Specifically, we examine whether the statistical distribution of the number of first team appearances by security analysts conforms to the Yule distribution, which implies that luck rather than differential talent explains success. This is an important issue since an analyst's position on the AART is an important determinant of the individual's pay and reputation. Our research results reject the Yule distribution. Thus, consistent with previous empirical studies by Stickel [Stickel, S. E. (1992). Reputation and performance among security analysis. J Finance 47, 1811–1836; Stickel, S. E. (1995). The anatomy of the performance of buy/sell recommendations. Financ Anal J 51, 25–39] and Brown and Chen [Brown, L. D., &amp; Chen, D.M. (1991). How good is the All‐American Research Team in forecasting earnings. J Bus Forecast 9, 14–18], we find that selection to the AART can be attributed to skill rather than luck.
Strain-Promoted 1,3-Dipolar Cycloaddition of Cycloalkynes and Organic Azides (2016)

A nearly forgotten reaction discovered more than 60 years ago-the cycloaddition of a cyclic alkyne and an organic azide, leading to an aromatic triazole-enjoys a remarkable popularity. Originally discovered out of pure chemical curiosity, and dusted off early this century as an efficient and clean bioconjugation tool, the usefulness of cyclooctyne-azide cycloaddition is now adopted in a wide range of fields of chemical science and beyond. Its ease of operation, broad solvent compatibility, 100 % atom efficiency, and the high stability of the resulting triazole product, just to name a few aspects, have catapulted this so-called strain-promoted azide-alkyne cycloaddition (SPAAC) right into the top-shelf of the toolbox of chemical biologists, material scientists, biotechnologists, medicinal chemists, and more. In this chapter, a brief historic overview of cycloalkynes is provided first, along with the main synthetic strategies to prepare cycloalkynes and their chemical reactivities. Core aspects of the strain-promoted reaction of cycloalkynes with azides are covered, as well as tools to achieve further reaction acceleration by means of modulation of cycloalkyne structure, nature of azide, and choice of solvent.
Metabolism of 10,11-dihydro-10-hydroxyimino-5H-dibenz/b, ƒ /azepine-5-carboxamide, a potent anti-epileptic drug (2002)

1. 10,11-Dihydro-10-hydroxyimino-5H-dibenzo/b, f/azepine-5-carboxamide (BIA 2-024) is a new anti-epileptic drug similar to oxcarbazepine (OXC) in structure and efficacy, but with a preferred pharmacodynamic profile. It possesses high in vitro activity, but since oximes are usually metabolized to their corresponding ketones, it is important to know whether its is vivo potency is a result of acting as a prodrug of OXC or if it is acting on its own. 2. The drug was given orally to rats, mice and rabbits, the metabolites identified and pharmacokinetic profiles compared between those species. Furthermore, the pharmacokinetic profile of the main metabolite was established in the rat. The results were compared to in vitro metabolism studies with liver microsomes from different mammalian species and humans. 3. In an atypical reaction for oximes, BIA 2-024 in rats was rapidly (t(max) = 2h) metabolized to the non-active 10-nitro-derivative (BIA 2-254), whereas rabbits and particularly mice oxidized the oxime moiety to a much lower extent. BIA 2-254 was then transformed to OXC and subsequently to the 10-hydroxy derivative and other minor metabolites. 4. In vitro data showed a very similar cross-species behaviour as the in vivo results; human liver microsomes catalysed the oxidation of BIA 2-024 to the nitro metabolite only at a low rate, and the same was observed for the subsequent metabolism to OXC. 5. The results allow prediction of the in vivo metabolism of BIA 2-024 in humans, where this drug is most likely absorbed efficiently and excreted mainly as the parent compound with a relatively low hepatic clearance. With the exception of rat, BIA 2-024 does not act as a prodrug of OXC.
Paclitaxel Encapsulated in Cationic Liposomes Increases Tumor Microvessel Leakiness and Improves Therapeutic Efficacy in Combination with Cisplatin (2008)

These data show that vascular targeting with EndoTAG-1 increases tumor microvessel leakiness probably due to vascular damage. This mechanism is not mediated by inflammatory leukocyte-endothelial cell interactions. Manipulating the blood-tumor barrier by repeated tumor microvessel targeting using EndoTAG-1 can effectively be combined with tumor cell-directed conventional cisplatin chemotherapy.
Detection of Calcified and Noncalcified Coronary Atherosclerotic Plaque by Contrast-Enhanced, Submillimeter Multidetector Spiral Computed Tomography (2003)

The results indicate the potential of MDCT to detect coronary atherosclerotic plaque in patients without significant coronary stenoses. However, further improvements in image quality will be necessary to achieve reliable assessment, especially of noncalcified plaque throughout the coronary tree.
Determination of thecis-trans isomerization barrier of severalL-peptidyl-L-proline dipeptides by dynamic capillary electrophoresis and computer simulation (2001)

Dynamic capillary electrophoresis (DCE) and computer simulation of the elution profiles with the theoretical plate and the stochastic model has been applied to determine the isomerization barriers of the three dipeptides L-alanyl-L-proline, L-leucyl-L-proline, and L-phenylalanyl-L-proline. The separation of the rotational cis-trans isomers has been performed in an aqueous 70 mM borate buffer at pH 9.5. Interconversion profiles featuring plateau formation and peak broadening were observed. To determine the rate constants k1 and k(-1) of the cis-trans isomerization in dynamic capillary electrophoresis, equations have been derived for the theoretical plate model and stochastic model. The electropherograms were simulated with the ChromWin software which uses the experimental data plateau height h(plateau), peak width at half height Wh, the total migration times of the cis-trans isomers tR and the electroosmotic break-through time t0 as well as the peak ratio [cis]/[trans]. From temperature-dependent measurements, the rate constants k1 and k(-1) and the kinetic activation parameters deltaG#, deltaH# and deltaS# of the cis-trans isomerization of the three dipeptides were obtained.
Cytologic differentiation between proliferative and nonproliferative breast disease in mammographically guided fine‐needle aspirates (1991)

Fine-needle aspiration biopsy (FNAB) is considered a valid diagnostic procedure in management of patients with breast lesions. It is also important to differentiate benign nonproliferative change from proliferative breast changes, since the risk of development of breast carcinoma in patients with atypical hyperplasia is 4-5 times that of general population. Therefore, the recognition of proliferative breast disease with atypia significantly impacts on the patient's subsequent management. To assess the feasibility of a cytologic grading system to further characterize benign breast lesions, cytologic preparation of 87 mammographically guided FNABs were studied. Cellular aspirates were evaluated for the cellular arrangement, the degree of cellular pleomorphism and anisonucleosis, presence of myoepithelial cells and nucleoli and the status of the chromatin pattern. Values ranging from 1 to 4 were assigned to each cytologic criterion, and a score based on the sum of the individual values was calculated for each case. The minimum score attainable was thus 6. In our chosen criteria cytologic diagnosis of nonproliferative disease was entertained when the total score ranged from 6 to 10. Proliferative disease without atypia was diagnosed with a total score ranging from 11 to 14. Atypical hyperplasia was reported when the total score ranged from 15 to 18. A cytologic diagnosis of malignancy was entertained when the total score ranged from 19 to 24. The cytologic diagnosis was then compared to the reported histologic diagnosis from the excisional biopsies and the data were statistically analysed. A high degree of concordance was found between the cytologic findings and the histologic diagnosis. This study suggests that it is possible to apply a cytologic grading system to further subclassify benign breast disease and distinguish these forms from neoplastic lesions.
A Unique Small Molecule Inhibitor of Enolase Clarifies Its Role in Fundamental Biological Processes (2013)

Enolase is a component of the glycolysis pathway and a "moonlighting" protein, with important roles in diverse cellular processes that are not related to its function in glycolysis. However, small molecule tools to probe enolase function have been restricted to crystallography or enzymology. In this study, we report the discovery of the small molecule "ENOblock", which is the first, nonsubstrate analogue that directly binds to enolase and inhibits its activity. ENOblock was isolated by small molecule screening in a cancer cell assay to detect cytotoxic agents that function in hypoxic conditions, which has previously been shown to induce drug resistance. Further analysis revealed that ENOblock can inhibit cancer cell metastasis in vivo. Moreover, an unexpected role for enolase in glucose homeostasis was revealed by in vivo analysis. Thus, ENOblock is the first reported enolase inhibitor that is suitable for biological assays. This new chemical tool may also be suitable for further study as a cancer and diabetes drug candidate.
The induction and suppression of prostaglandin H2 synthase (cyclooxygenase) in human monocytes. (1990)

We report here that the bacterial lipopolysaccharide endotoxin induces human blood monocytes in a time- and dose-dependent manner to release prodigious amounts of prostaglandins with thromboxane A2, the major metabolite formed. Cells responded to as little as 1 ng/ml lipopolysaccharide to release prostaglandin E2 and thromboxane A2 with maximal stimulation at 10 micrograms/ml. Lipopolysaccharide was found to induce increased activity of cyclooxygenase enzyme without affecting the activities of phospholipase and thromboxane synthase or the formation of 5-lipoxygenase products (e.g. leukotriene B4). The glucocorticoid dexamethasone completely blocked the lipopolysaccharide-induced prostanoid release by inhibiting the activity of monocyte cyclooxygenase. Dexamethasone did not affect phospholipase and thromboxane synthase activities or leukotriene formation. Immunoprecipitation of [35S]methionine-labeled cyclooxygenase confirmed that the effect of lipopolysaccharide and dexamethasone on the monocyte prostanoid production could be attributed to an increase or decrease, respectively, in cellular cyclooxygenase de novo synthesis.
DC++: distributed object-oriented system support on top of OSF DCE (1993)

The OSF Distributed Computing Environment (DCE) is becoming an industry standard for open distributed computing. DCE only supports client/server-style applications based on the remote procedure call (RPC) communication model. The authors describe the design and implementation of an extended distributed object-oriented environment, DC++, on top of DCE. As opposed to RPC, it supports a uniform object model, location independent invocation of fine-grained objects, remote reference parameter passing, dynamic migration of objects between nodes, and C++ language integration. Moreover, the implementation is fully integrated with DCE, using DCE UUIDs for object identification, DCE threads for interobject concurrency, DCE RPC for remote object invocation, and the DCE Cell Directory Service (CDS) for optional retrieval of objects by name. An additional stub compiler enables automatic generation of C++-based object communication interfaces. Low-level parameter encoding is done by DCE RPC's stub generation facility using the C-based DCE interface definition language (IDL).
The bHLH gene Hes1 is essential for expansion of early T cell precursors (1999)

Mice mutant for the bHLH gene Hes1, which is known to keep cells in a proliferative state, mostly lack thymus. Transfer of Hes1-null fetal liver cells into RAG2-null host mice normally reconstitutes B cells but fails to generate mature T cells in the thymus. In the reconstituted thymus, T cell differentiation is arrested at the CD4(-)CD8(-) double negative (DN) stage. Both the initial T cell receptor (TCR)-independent and the subsequent TCR-dependent selective expansion during the DN stage are severely affected. Thus, Hes1 is essential for the earliest thymocyte expansion in a cell-autonomous manner.