gebhart/patrepeval huggingface dataset:
Expression, purification and characterization of the second Kunitz‐type protease inhibitor domain of the human WFIKKN protein (2003)

Recently we have described a novel secreted protein (the WFIKKN protein) that consists of multiple types of protease inhibitory modules, including two tandem Kunitz-type protease inhibitor-domains. On the basis of its homologies we have suggested that the WFIKKN protein is a multivalent protease inhibitor that may control the action of different proteases. In the present work we have expressed the second Kunitz-type protease inhibitor domain of the human protein WFIKKN in Escherichia coli, purified it by affinity chromatography on trypsin-Sepharose and its structure was characterized by CD spectroscopy. The recombinant protein was found to inhibit trypsin (Ki = 9.6 nm), but chymotrypsin, elastase, plasmin, pancreatic kallikrein, lung tryptase, plasma kallikrein, thrombin, urokinase or tissue plasminogen activator were not inhibited by the recombinant protein even at 1 microm concentration. In view of the marked trypsin-specificity of the inhibitor it is suggested that its physiological target may be trypsin.
Constrained Delaunay triangulations (1987)

Given a set of n vertices in the plane together with a set of noncrossing edges, the constrained Delaunay triangulation (CDT) is the triangulation of the vertices with the following properties: (1) the prespecified edges are included in the triangulation, and (2) it is as close as possible to the Delaunay triangulation. We show that the CDT can be built in optimal Ο(n log n) time using a divide-and-conquer technique. This matches the time required to build an arbitrary (unconstrained) Delaunay triangulation and the time required to build an arbitrary constrained (nonDelaunay) triangulation. CDTs, because of their relationship with Delaunay triangulations, have a number of properties that should make them useful for the finite-element method. Applications also include motion planning in the presence of polygonal obstacles in the plane and constrained Euclidean minimum spanning trees, spanning trees subject to the restriction that some edges are prespecified.
Unfavorable cerebral venous outflow is associated with futile recanalization in acute ischemic stroke patients (2023)

We observe that unfavorable VO on admission CTA is a strong predictor of unfavorable functional outcomes despite successful vessel recanalization in AIS-LVO patients. Assessment of VO profiles could help as a pretreatment imaging biomarker to determine patients at risk for futile recanalization.
G-Quadruplex on Oligo Affinity Support (G4-OAS): An Easy Affinity Chromatography-Based Assay for the Screening of G-Quadruplex Ligands (2014)

A simple, cheap, and highly reproducible affinity chromatography-based method has been developed for the screening of G-quadruplex binders. The tested compounds were flowed through a polystyrene resin functionalized with an oligonucleotide able to form, in proper conditions, a G-quadruplex structure. Upon cation-induced control of the folding/unfolding processes of the immobilized G-quadruplex-forming sequence, small molecules specifically interacting with the oligonucleotide structure were first captured and then released depending on the used working solution. This protocol, first optimized for different kinds of known G-quadruplex ligands and then applied to a set of putative ligands, has allowed one to fully reuse the same functionalized resin batch, recycled for several tens of experiments without loss in efficiency and reproducibility.
Src family tyrosine kinases regulate adhesion-dependent tyrosine phosphorylation of 5′-inositol phosphatase SHIP2 during cell attachment and spreading on collagen I (2002)

Inositol phosphatases play an important role in regulation of cellular levels of lipid second messengers. Recently we have reported a novel function for SHIP2 in cell adhesion and spreading. In this study, we further characterize the adhesion-dependent tyrosine phosphorylation of SHIP2 and examine the role of Src family tyrosine kinases in the regulation of SHIP2 function. SHIP2 was tyrosine phosphorylated during cell attachment and spreading on collagen I, but not on fibronectin, collagen IV, laminin or poly-L-lysine. SHIP2 tyrosine phosphorylation, induced by plating on a collagen-I-coated surface but not by epidermal growth factor or insulin treatment of cells, was completely blocked by small molecule inhibitors of Src family kinases. SHIP2 could be phosphorylated in vitro by recombinant Src kinase and tyrosines 986-987 in the NPXY motif of SHIP2 appear to be the major sites of phosphorylation for Src both in vitro and in vivo. An activated form of Src induced strong tyrosine phosphorylation of SHIP2 while a dominant-negative form decreased collagen-I-dependent SHIP2 phosphorylation. SHIP2 associated with the adapter protein Shc via its NPXY motif during cell spreading on collagen I in a Src activity-dependent manner. Expression of SHIP2 with mutated NPXY motif caused deregulation of lamellipodia formation during spreading on collagen I. These observations indicate that SHIP2 is regulated by Src family kinases during cell attachment and spreading on collagen I and suggest an important role for SHIP2 as a part of a signaling pathway that regulates actin cytoskeleton remodeling.
InGaN-based 405 nm near-ultraviolet light emitting diodes on pillar patterned sapphire substrates (2010)

A study of GaN films and nitride based light emitting diodes (LEDs) grown on low density pillar structure (LDPS) and high density pillar structure (honeycomb like) sapphires patterned by chemical wet etching is described. Both types of patterned sapphire substrate (PSS) offered reduced defect density and improved performance of near-ultraviolet LED. In the case of LDPS patterned sapphire the correct choice of the pillar depth was found to be crucial for high quality crystal growth. A reduction of threading dislocation (TD) density from the level of 108 cm−2 down to the level of 2 × 109 cm−2 was observed. It was found that mostly enhanced light extraction rather than improved material quality caused the improvement of the LED performance.
Many-Body Quantum Calculations for Graphyne for Electronic Devices (2020)

Moving beyond traditional 2D materials is now desirable to have switching capabilities (e.g., transistors). Here we propose using graphyne because, as we will show in this letter, obtaining regions of the electronic bandstructure which act as valence and conduction bands, with an apparent bandgap, is found. Here for particular allotropes of graphyne, density of states (DOS) and electronic bandstructure diagrams with E(k) vs k are found for the graphyne allotropes graphyne-1 and graphyne-2 having, respectively, one and two triple C-C carbon-carbon bonds between adjoining benzene rings. The ab initio many-body quantum calculations were performed using both local density approximation (LDA) and generalized gradient approximation (GGA) for density functional theory (DFT).
[Intraoperative thermography--temperature range on the heart surface during cold cardioplegia]. (2003)

The paper presents the temperature analysis of the myocardial surface at the cohort of 11 patients with coronary artery disease, who underwent coronary artery bypass grafting with cardiopulmonary bypass. Left and right ventricle temperature changes were registered with Agema Thermovision 900 SW/TE system during cold cardioplegia infusion. Cardioplegia was delivered by the coronary sinus and by the aortic root. An individual pattern of cardioplegia distribution was found. The differences in the temperature of the right and left ventricle correlated with the presence of the critical coronary artery stenosis.
Connective tissue response to immobility (1975)

The biomechanical changes in rabbit knee contractures were measured after 9 weeks of immobilization. These results were correlated with the biochemical composition of periarticular connective knee tissue of the same knees. The loss of total hexosamine correlates significantly with joint stiffness on an animal-to-animal basis. Total hexosamine also correlates with the energy required cyclicly to flex and to extend the experimental joints. Of the individual glycosaminoglycan fractions, only hyaluronic acid showed significant correlation with the biomechanical data. The possible mechanism of contracture formation was postulated based on these results.
Broadband cw-terahertz spectroscopy for characterizing reactive plasmas (2019)

Abstract Terahertz spectroscopy is seeing increasing use in analytical chemistry because of its ability to access ground state molecular rotational and vibrational transitions. Experiments reported on the use of THz spectroscopy to the studies of low pressure plasmas have focused on the use of pulsed sources, which have limited spectral resolution. These are suitable in the characterization of plasma parameters such as electron density, but somewhat inadequate in the study of molecular absorption spectra. The recent commercial availability of continuous THz sources with much higher spectral resolution has afforded the detailed probing of molecular absorption features but they have not yet been exploited in studies of low pressure plasma chemistry. One of the major benefits of continuous-wave THz spectroscopy (cw-TS) compared to optical and infrared methods is its applicability to the study of both plasma chemistry as well as parameters, i.e. electron density and collision frequency. In this article, we provide first insights into the use of cw-TS as a plasma diagnostic, and demonstrate the opportunities and challenges by example measurements in a low-pressure argon-methanol radio frequency inductively coupled plasma in which we estimate both the plasma-induced dissociation in the precursor methanol concentration, as well as the electron density and momentum scattering collision frequency.
Coexpression of neuroendocrine markers and epithelial cytoskeletal proteins in bronchopulmonary neuroendocrine neoplasms. (1985)

Neuroendocrine (NE) neoplasms of the human bronchopulmonary tract were examined by electron microscopy, immunocytochemistry, and gel electrophoresis of cytoskeletal proteins from microdissected tissue samples. All samples (carcinoids, well-differentiated NE carcinoma, NE carcinomas of intermediate type, NE carcinomas of the small cell type) contained significant numbers of cells that immunostained for one or more of the following neuroendocrine markers tested: bombesin, calcitonin, ACTH, leu-enkephalin, gastrin, serotonin, somatostatin, alpha-melanocyte-stimulating hormone, vasoactive intestinal peptide, glucagon, insulin, substance P, and neuron-specific enolase. Electron microscopy revealed typical NE cell features, including variable abundant and frequently heterogeneous neurosecretory granules. Tumor cells contained filaments specifically stained with different conventional and monoclonal antibodies to cytokeratins and displayed punctate plasma membrane staining with antibodies to desmoplakins, in agreement with the electron microscopic demonstration of tonofilament bundles and desmosomes. Immunocytochemistry for NE markers and cytoskeletal proteins on consecutive sections revealed both cytokeratins and neuroendocrine substances in single cells. Using gel electrophoresis of cytoskeletal proteins of tissue regions extracted with high salt buffer and detergent, we could detect, in the tumors tested, appreciable amounts of cytokeratin polypeptides 8, 18, and 19, i.e., major cytokeratins also found in certain other lung carcinomas such as adenocarcinomas. Tumor cells were not significantly stained with antibodies to other intermediate filament proteins such as vimentin, desmin, glial filament protein, and neurofilament protein. The results show that NE substances can be synthesized in cells containing a typical epithelial cytoskeleton, i.e., cytokeratin filaments and desmosomes. These findings support the notion of an epithelial character of these tumors and appear in contrast with recent reports that neurofilaments are the only type of intermediate filaments present in carcinoids and other pulmonary NE tumors. These observations may have important implications for the histogenesis of NE carcinomas and for diagnostic pathology.
Phase II study of alemtuzumab in lymphoplasmacytic lymphoma: Results of WMCTG trial 02–079 (2006)

7523 Background: Alemtuzumab (Campath-1H) is a fully humanized anti-CD52 antibody used to treat B and T-cell disorders. CD52 is widely expressed on bone marrow lymphoplasmacytic cells and growth supporting mast cells in patients with lymphoplasmacytic lymphoma (LPL), including Waldenstrom’s macroglobulinemia (WM). We therefore examined the activity of alemtuzumab in LPL. Methods: 28 patients with LPL, including 27 WM patients were enrolled in this multicenter study. 23 patients were previously treated. Median age was 60 (range 33–75 years), median prior therapies was 2 (range 0–5), and median time from diagnosis was 2.9 (range 0.1–9.0 years). Baseline median bone marrow involvement was 30% (range 5–90%), median serum IgM was 3510 (range 622–12,000 mg/dL) and hematocrit was 35.1 (range 24.4–42.8%). Patients received 3 test doses of alemtuzumab (3, 10, and 30mg IV) followed by 30 mg TIW for up to 12 weeks. All patients received acyclovir and bactrim or equivalent prophylaxis. Results: Twenty-five patients are evaluable for response. 24/25 patients demonstrated a decrease in serum IgM levels (median change -40.5%), for an overall response rate of 76%, which included 8 (32%) partial responders (≤50% decrease in serum IgM), and 11 (44%) minor responders (≥25% decrease in serum IgM). Hematological toxicities were common among previously treated (but not untreated) patients and included G3/4 neutropenia 39%; thrombocytopenia 18%; anemia 7%. G3/4 non-hematological toxicity for all patients included dermatitis 11%; fatigue 7%; and infection 7%. CMV reactivation and infection was commonly seen among previously treated patients and may have been etiological for one death on study. Two other patients also succumbed on study, one related in part to drug therapy for CMV infection and another due to complications of therapy induced thrombocytopenia and Von Willebrand disease. With a median follow-up of 8.5+ months, 11/19 responding patients remain free of progression. Conclusions: Alemtuzumab is highly active in patients with LPL. Hematological and non-hematological toxicities, including CMV reactivation and infection are common among previously treated patients. Further exploration of this agent in LPL, including upfront therapy is warranted. No significant financial relationships to disclose.
Effects of pioglitazone on calcium channels in vascular smooth muscle. (1994)

Pioglitazone, an insulin-sensitizing, antidiabetic agent, has blood pressure-lowering effects in insulin-resistant hypertensive rats and attenuates growth factor-induced increases of intracellular Ca2+ in rat aortic vascular smooth muscle cells. To determine whether modulation of voltage-dependent Ca2+ channels plays a role in this association, we investigated the effects of pioglitazone on voltage-dependent current in cultured rat aortic (a7r5) and freshly dissociated rat tail artery vascular smooth muscle cells. Both cell types were studied with whole-cell patch-clamp techniques. Current through L-type Ca2+ channels was elicited with a voltage ramp in the presence of Ba2+ substituted for Ca2+. T-type Ca2+ current was studied using a two-pulse protocol that enabled the isolation of transient current. In a7r5 vascular smooth muscle cells, 2-minute application of pioglitazone (5 and 10 mumol/L) reduced L-type current by 7.9 +/- 1.0% (n = 8) (mean +/- SEM, number of cells) and 14.5 +/- 3.0% (n = 9) (P < .01, two-tailed paired t test), respectively. In contrast, 2-minute application of pioglitazone had no significant effect on T-type Ca2+ current. In freshly dissociated tail artery vascular smooth muscle cells, 2-minute application of 10 mumol/L pioglitazone had an insignificant effect (4.8 +/- 5.6% reduction); however, 25 mumol/L pioglitazone reduced L-type current by 27.3 +/- 7.2% (n = 5) (P < .01). Two-minute application of 0.1% or 0.2% dimethyl sulfoxide (vehicle) alone had no significant effects on currents in either type of vascular smooth muscle cell.(ABSTRACT TRUNCATED AT 250 WORDS)
<title>Improved instrumentation for photodynamic fluorescence detection of cancer</title> (1991)

A fluorescence-detection technique for cancer in human hollow organs has been developed based on endoscope-assisted two-wavelength excitation of the polyporphyrin Photofrin II in tissue. Due to the photosensitizing capability of the fluorescent tumormarket the applied dose is reduced to 0.4 mg/kg bw which avoids photosensitization of the patient''s skin. Fluorescence is detected either spectrally resolved by means of an optical multichannel analyzer or by imaging of diseased tissue areas with an intensified video system. The fluorescence pattern in the final image is presented with high contrast due to realtime subtraction of nonspecific background signals.
Genetic fusion of subunits of a dimeric protein substantially enhances its stability and rate of folding. (1993)

The gene V protein of bacteriophage f1 is a single-stranded DNA and RNA-binding protein composed of two identical subunits. We have constructed single-chain variants of the protein using short peptide linkers of five or six amino acids to connect the carboxyl terminus of one monomer to the amino terminus of the second monomer. The resulting subunit-fusion gene V proteins were found to bind single-stranded DNA nearly as tightly as the wild-type protein. Denaturation measurements show that the subunit-fusion gene V proteins are 5 kcal/mol (1 kcal = 4.18 kJ) more stable than the wild-type protein at a protein concentration of 10 microM. The rate of unfolding of the protein is essentially unaffected by the fusion of monomeric subunits, whereas the rate of folding is greatly enhanced. Our results suggest a simple way of obtaining a substantial thermodynamic stabilization for some oligomeric proteins.
Linkage of congenital isolated adrenocorticotropic hormone deficiency to the corticotropin releasing hormone locus using simple sequence repeat polymorphisms (1996)

Genetic screening techniques using simple sequence repeat polymorphisms were applied to investigate the molecular nature of congenital isolated adrenocorticotropic hormone (ACTH) deficiency. We hypothesize that this rare cause of hypocortisolism shared by a brother and sister with two unaffected sibs and unaffected parents is inherited as an autosomal recessive single gene mutation. Genes involved in the hypothalamic-pituitary axis controlling cortisol sufficiency were investigated for a causal role in this disorder. Southern blotting showed no detectable mutations of the gene encoding pro-opiomelanocortin (POMC), the ACTH precursor. Other candidate genes subsequently considered were those encoding neuroendocrine convertase-1, and neuroendocrine convertase-2 (NEC-1, NEC-2), and corticotropin releasing hormone (CRH). Tests for linkage were performed using polymorphic di- and tetranucleotide simple sequence repeat markers flanking the reported map locations for POMC, NEC-1, NEC-2, and CRH. The chromosomal haplotypes determined by the markers flanking the loci for POMC, NEC-1, and NEC-2 were not compatible with linkage. However, 22 individual markers defining the chromosomal haplotypes flanking CRH were compatible with linkage of the disorder to the immediate area of this gene on chromosome 8. Based on these data, we hypothesize that the ACTH deficiency in this family is due to an abnormality of CRH gene structure or expression. These results illustrate the useful application of high density genetic maps constructed with simple sequence repeat markers for inclusion/exclusion studies of candidate genes in even very small nuclear families segregating for unusual phenotypes.
ChemInform Abstract: PHOSPHORUS‐NITROGEN COMPOUNDS PART 18, HYDRAZIDES AND THIOSEMICARBAZIDES (1975)

Abstract Phosphon‐ und Phosphorsäure‐Derivate (I), (VI), (VIII) und (XI) reagieren mit Hydrazinen (II) und (IV) zu den Hydraziden (III), (V), (VII), (IX), (X), (XII) und (XIII).
Sensing Properties of Chipless RFID Tags Based on Nanomaterials (2011)

International audience
Let there be hair (2011)

The trademark look of Rapunzel in Disney's Tangled presented unique challenges in grooming, animation, rendering, and pipeline management. Her hair was highly art directed and seventy feet long. The length of the hair, the amount of screen space it occupied, and the role it played within the film necessitated advanced planning in order to treat it very much as if it were a character. This talk discusses the original hair roadmap and changes required during production.
Nicotinamide–Ponatinib Analogues as Potent Anti-CML and Anti-AML Compounds (2020)

Ponatinib is a multikinase inhibitor that is used to treat chronic myeloid leukemia patients harboring mutated ABL1(T315I) kinase. Due to the potent inhibition of FLT3, RET, and fibroblast growth factor receptors (FGFRs), it is also being evaluated against acute myeloid leukemia (AML), biliary, and lung cancers. The multikinase inhibition profile of ponatinib may also account for its toxicity, thus analogs with improved kinase selectivity or different kinase inhibition profiles could be better tolerated. The introduction of nitrogen into drug compounds can enhance efficacy and drug properties (a concept called "necessary nitrogen"). Here, we introduce additional nitrogen into the benzamide moiety of ponatinib to arrive at nicotinamide analogs. A nicotinamide analogue of ponatinib, HSN748, retains activity against FLT3, ABL1, RET, and PDGFRα/β but loses activity against c-Src and P38α. MNK1 and 2 are key kinases that phosphorylate eIF4E to regulate the protein translation complex. MNK also modulates mTORC1 signaling and contributes to rapamycin resistance. Inhibitors of MNK1 and 2 are being evaluated for anticancer therapy. Ponatinib is not a potent inhibitor of MNK1 or 2, but the nicotinamide analogs are potent inhibitors of MNKs. This illustrates a powerful demonstration of the necessary nitrogen concept to alter both the potency and selectivity of drugs.
Quantitative analysis of multivalent interactions of carbohydrate-encapsulated gold nanoparticles with concanavalin AElectronic supplementary information (ESI) available: detailed experimental procedures, SPR response curves and compound characterization data. See http://www.rsc.org/suppdata/cc/b3/b308995a/ (2003)

Multivalent interactions between carbohydrate-encapsulated gold nanoparticles and Con A are found with high affinity and specificity.
Mechanisms of lipid malabsorption in Cystic Fibrosis: the impact of essential fatty acids deficiency (2005)

Transport mechanisms, whereby alimentary lipids are digested and packaged into small emulsion particles that enter intestinal cells to be translocated to the plasma in the form of chylomicrons, are impaired in cystic fibrosis. The purpose of this paper is to focus on defects that are related to intraluminal and intracellular events in this life-limiting genetic disorder. Specific evidence is presented to highlight the relationship between fat malabsorption and essential fatty acid deficiency commonly found in patients with cystic fibrosis that are often related to the genotype. Given the interdependency of pulmonary disease, pancreatic insufficiency and nutritional status, greater attention should be paid to the optimal correction of fat malabsorption and essential fatty acid deficiency in order to improve the quality of life and extend the life span of patients with cystic fibrosis.