gebhart/patrepeval huggingface dataset:
Acquisition of transforming properties by FYN, a normal SRC-related human gene. (1988)

The SRC gene is the prototype for a family of closely related genes whose products have protein-tyrosine kinase activity. We recently described another member of this family, designated FYN, whose cDNA was isolated from normal human fibroblasts. To examine the possible role of FYN as an oncogene, we investigated the effects of FYN overexpression on NIH 3T3 cells. Our findings demonstrate that normal FYN overexpression induces morphologic transformation and anchorage-independent growth. In addition, at relatively low frequency, FYN acquired properties of a dominant-acting oncogene capable of inducing the fully tumorigenic phenotype. Genetic changes associated with the conversion of normal FYN cDNA into a transforming gene with high focus-forming activity were localized to the carboxyl-terminal region of its translational product.
Synthesis andin VitroEvaluation of Two Progressive Series of Bifunctional Polyhydroxybenzamide Catechol-O-methyltransferase Inhibitors (1997)

Two progressive series of molecules with two polyhydroxybenzamide substructures were synthesized and tested as potential inhibitors of catechol-O-methyltransferase (COMT). These compounds were designed for the purpose of enhanced enzyme binding with duplicated substructures separated by a linker section of various lengths. Our results show that potency and mode of inhibition observed with the "bifunctional" compounds were a reflection of their bifunctional nature. Furthermore, potency and mode of inhibition were dependent on the length of the linker section. Of the assayed compounds, the optimum linker was found to be diaminopropane. For example, N,N'-1,3-propanediylbis(3,4-dihydroxybenzamide) and N,N'-1,3-propanediylbis(3,4,5-trihydroxybenzamide) demonstrated strong inhibitory action against COMT, with apparent Ki values of 0.3 and 6.0 microM, respectively.
Image databases: a case study in Norwegian silver authentication (1996)

Establishing the identity of the craftsmen of old Norwegian silver objects can be accomplished through the recognition of master-marks. Manually searching through the 6000 master-marks and 250 city-marks is tedious and unreliable. Our-goal is to develop an efficient retrieval of images of master- and city-marks from large databases based on the shape content of the image. We are building an automatic retrieval system to browse through the entire database. The first step is to extract primitive visual features from the images and to retrieve images on the basis of these features. We have developed a prototype image database of master-marks from a catalog by scanning 171 of these marks which appear on silver tankards. We have successfully extracted shape features from these marks and matched master-marks in the database against the unknown query images. Initial experiments on master-marks are encouraging. The same shape-based matching techniques are used to match city-marks. Our future work will involve building an expert system for a stylistic analysis of the silver tankards.
Structural Coupling of SH2-Kinase Domains Links Fes and Abl Substrate Recognition and Kinase Activation (2008)

The SH2 domain of cytoplasmic tyrosine kinases can enhance catalytic activity and substrate recognition, but the molecular mechanisms by which this is achieved are poorly understood. We have solved the structure of the prototypic SH2-kinase unit of the human Fes tyrosine kinase, which appears specialized for positive signaling. In its active conformation, the SH2 domain tightly interacts with the kinase N-terminal lobe and positions the kinase alphaC helix in an active configuration through essential packing and electrostatic interactions. This interaction is stabilized by ligand binding to the SH2 domain. Our data indicate that Fes kinase activation is closely coupled to substrate recognition through cooperative SH2-kinase-substrate interactions. Similarly, we find that the SH2 domain of the active Abl kinase stimulates catalytic activity and substrate phosphorylation through a distinct SH2-kinase interface. Thus, the SH2 and catalytic domains of active Fes and Abl pro-oncogenic kinases form integrated structures essential for effective tyrosine kinase signaling.
Physically Unclonable Functions Constructions, Properties and Applications (2013)

Physically unclonable functions (PUFs) are innovative physical security primitives that produce unclonable and inherent instance-specific measurements of physical objects; in many ways they are the inanimate equivalent of biometrics for human beings. Since they are able to securely generate and store secrets, they allow us to bootstrap the physical implementation of an information security system. In this book the author discusses PUFs in all their facets: the multitude of their physical constructions, the algorithmic and physical properties which describe them, and the techniques required to deploy them in security applications. The author first presents an extensive overview and classification of PUF constructions, with a focus on so-called intrinsic PUFs. He identifies subclasses, implementation properties, and design techniques used to amplify submicroscopic physical distinctions into observable digital response vectors. He lists the useful qualities attributed to PUFs and captures them in descriptive definitions, identifying the truly PUF-defining properties in the process, and he also presents the details of a formal framework for deploying PUFs and similar physical primitives in cryptographic reductions. The author then describes a silicon test platform carrying different intrinsic PUF structures which was used to objectively compare their reliability, uniqueness, and unpredictability based on experimental data. In the final chapters, the author explains techniques for PUF-based entity identification, entity authentication, and secure key generation. He proposes practical schemes that implement these techniques, and derives and calculates measures for assessing different PUF constructions in these applications based on the quality of their response statistics. Finally, he presents a fully functional prototype implementation of a PUF-based cryptographic key generator, demonstrating the full benefit of using PUFs and the efficiency of the processing techniques described. This is a suitable introduction and reference for security researchers and engineers, and graduate students in information security and cryptography.
Enhanced Optical Transmission Mediated by Localized Plasmons in Anisotropic, Three-Dimensional Nanohole Arrays (2010)

This paper describes three-dimensional (3D) nanohole arrays whose high optical transmission is mediated more by localized surface plasmon (LSP) excitations than by surface plasmon polaritons (SPPs). First, LSPs on 3D hole arrays lead to optical transmission an order of magnitude higher than 2D planar hole arrays. Second, LSP-mediated transmission is broadband and more tunable than SPP-enhanced transmission, which is restricted by Bragg coupling. Third, for the first time, two types of surface plasmons can be selectively excited and manipulated on the same plasmonic substrate. This new plasmonic substrate fabricated by high-throughput nanolithography techniques paves the way for cutting-edge optoelectronic and biomedical applications.
Micro-invasive glaucoma surgery (MIGS): a review of surgical procedures using stents (2017)

Abstract: Over the last decade several novel surgical treatment options and devices for glaucoma have been developed. All these developments aim to cause as little trauma as possible to the eye, to safely, effectively, and sustainably reduce intraocular pressure (IOP), to produce reproducible results, and to be easy to adopt. The term “micro-invasive glaucoma surgery (MIGS)” was used for summarizing all these procedures. Currently MIGS is gaining more and more interest and popularity. The possible reduction of the number of glaucoma medications, the ab interno approach without damaging the conjunctival tissue, and the probably safer procedures compared to incisional surgical methods may explain the increased interest in MIGS. The use of glaucoma drainage implants for lowering IOP in difficult-to-treat patients has been established for a long time, however, a variety of new glaucoma micro-stents are being manufactured by using various materials and are available to increase aqueous outflow via different pathways. This review summarizes published results of randomized clinical studies and extensive case report series on these devices, including Schlemm’s canal stents (iStent ® , iStent ® inject, Hydrus), suprachoroidal stents (CyPass ® , iStent ® Supra), and subconjunctival stents (XEN). The article summarizes the findings of published material on efficacy and safety for each of these approaches. Keywords: glaucoma, micro-invasive glaucoma surgery, MIGS, iStent, iStent inject, CyPass, Hydrus, XEN Corrigendum for this paper has been published
Characterization of Scavengers of γ-Ketoaldehydes That Do Not Inhibit Prostaglandin Biosynthesis (2009)

Expression of cyclooxygenase-2 (COX-2) is associated with the development of many pathologic conditions. The product of COX-2, prostaglandin H(2) (PGH(2)), can spontaneously rearrange to form reactive gamma-ketoaldehydes called levuglandins (LGs). This gamma-ketoaldehyde structure confers a high degree of reactivity on the LGs, which rapidly form covalent adducts with primary amines of protein residues. Formation of LG adducts of proteins has been demonstrated in pathologic conditions (e.g., increased levels in the hippocampus in Alzheimer's disease) and during physiologic function (platelet activation). On the basis of knowledge that lipid modification of proteins is known to cause their translocation and to alter their function, we hypothesize that modification of proteins by LG could have functional consequences. Testing this hypothesis requires an experimental approach that discriminates between the effects of protein modification by LG and the effects of cyclooxygenase-derived prostanoids acting through their G-protein coupled receptors. To achieve this goal, we have synthesized and evaluated a series of scavengers that react with LG with a potency more than 2 orders of magnitude greater than that with the epsilon-amine of lysine. A subset of these scavengers are shown to block the formation of LG adducts of proteins in cells without inhibiting the catalytic activity of the cyclooxygenases. Ten of these selective scavengers did not produce cytotoxicity. These results demonstrate that small molecules can scavenge LGs in cells without interfering with the formation of prostaglandins. They also provide a working hypothesis for the development of pharmacologic agents that could be used in experimental animals in vivo to assess the pathophysiological contribution of levuglandins in diseases associated with cyclooxygenase up-regulation.
Interleukin 6 induces a liver-specific nuclear protein that binds to the promoter of acute-phase genes. (1989)

Interleukin 6 (IL-6) is responsible for a variety of biological effects related to the activation of defenses against infection or inflammation, including the immune response and the acute-phase reaction. Its mechanism of action is unknown. It has recently been shown to induce transcription of several genes encoding acute-phase proteins. Here we describe the identification of an IL-6 responsive element (IL-6RE) present in the promoter of the human hemopexin gene. This element is necessary and sufficient for the IL-6-dependent activation of transcription. The IL-6 effect does not require de novo protein synthesis. A liver-specific nuclear protein (IL-6DBP) binds to the hemopexin IL-6RE as well as to similar sequences on the promoter of other acute-phase genes. IL-6DBP DNA binding activity is induced by IL-6 via a posttranslational mechanism.
The contour of the femoral head-neck junction as a predictor for the risk of anterior impingement (2002)

Impingement by prominence at the femoral head-neck junction on the anterior acetabular rim may cause early osteoarthritis. Our aim was to develop a simple method to describe concavity at this junction, and then to test it by its ability to distinguish quantitatively a group of patients with clinical evidence of impingement from asymptomatic individuals who had normal hips on examination. MR scans of 39 patients with groin pain, decreased internal rotation and a positive impingement test were compared with those of 35 asymptomatic control subjects. The waist of the femoral head-neck junction was identified on tilted axial MR scans passing through the centre of the head. The anterior margin of the waist of the femoral neck was defined and measured by an angle (α). In addition, the width of the femoral head-neck junction was measured at two sites. Repeated measurements showed good reproducibility among four observers. The angle α averaged 74.0° for the patients and 42.0° for the control group (p &lt; 0.001). Significant differences were also found between the patient and control groups for the scaled width of the femoral neck at both sites. Using standardised MRI, the symptomatic hips of patients who have impingement have significantly less concavity at the femoral head-neck junction than do normal hips. This test may be of value in patients with loss of internal rotation for which a cause is not found.
The epidermal growth factor receptor family as a central element for cellular signal transduction and diversification. (2001)

Homeostasis of multicellular organisms is critically dependent on the correct interpretation of the plethora of signals which cells are exposed to during their lifespan. Various soluble factors regulate the activation state of cellular receptors which are coupled to a complex signal transduction network that ultimately generates signals defining the required biological response. The epidermal growth factor receptor (EGFR) family of receptor tyrosine kinases represents both key regulators of normal cellular development as well as critical players in a variety of pathophysiological phenomena. The aim of this review is to give a broad overview of signal transduction networks that are controlled by the EGFR superfamily of receptors in health and disease and its application for target-selective therapeutic intervention. Since the EGFR and HER2 were recently identified as critical players in the transduction of signals by a variety of cell surface receptors, such as G-protein-coupled receptors and integrins, our special focus is the mechanisms and significance of the interconnectivity between heterologous signalling systems.
Recognition and Pose Estimation of Rigid Transparent Objects with a Kinect Sensor (2012)

Recognizing and determining the 6DOF pose of transparent objects is necessary in order for robots to manipulate such objects. However, it is a challenging problem for computer vision. We propose new algorithms for segmentation, pose estimation and recognition of transparent objects from a single RGB-D image from a Kinect sensor. Kinect's weakness in the perception of transparent objects is exploited in their segmentation. Following segmentation, edge fitting is used for recognition and pose estimation. A 3D model of the object is created automatically during training and it is required for pose estimation and recognition.
Secondary injury mechanisms in acute spinal cord injury. (1993)

Experimental studies in animal spinal cord injury models suggest that preservation of a relatively small number of spinal axons can support neurological recovery. The second National Acute Spinal Cord Injury Study (NASCIS 2) was the first clinical trial to demonstrate that a treatment given after injury can enhance neurological recovery. In this trial, patients treated with high-dose methylprednisolone within 8 hours of spinal cord injury recovered more sensory and motor function than did those treated with placebo. In addition to demonstrating the first effective pharmacological intervention in central nervous system injury, NASCIS 2 identified several critical issues that must be investigated in future preclinical and clinical research. These include drug dose, initiation time, and duration of treatment, as well as combination therapy and injury severity. Addressing these issues systematically will require more reproducible animal models and more accurate outcome measures.
Performance of an Immobilized Trypsin System for Improving Oxidative Stability of Milk (1975)

Cold raw milk with .1 ppm of added copper was pumped at a rate of 2 liters/ h through a bed of 20 g of glass-bound trypsin for 5 h daily for 14 days. After each daily run the reactor was backwashed with distilled water, flooded with 20% ethanol in phosphate buffer, and refrigerated. Samples were pasteurized, stored 6 days, and tested for oxidation. All copper-containing samples were protected from oxidation by the treatment. The bound enzyme showed no loss of activity over the 14 days as determined by N-benzoyl-L-arginine ethyl ester hydrolysis. Standard plate counts ~ ethanol solution after storage, aqueous washing, and the milk before and after the treatment showed that 20% ethanol was effective in limiting microbial growth, that there was no microbial build-up in the reactor during the 5 h of continuous milk passage, and that milk was not substantially eontaminated by the treatment. Flow rate decreased with time whether the reactor was used as a packed column or a fluidized bed due to plugging of the column or the retaining screen. No increase in nonprotein nitrogen in the treated samples was detected. However, when casein was used as the substrate, increases in nonprotein nitrogen and free amino groups were appreciable.
Oleate Reverses Palmitate-induced Insulin Resistance and Inflammation in Skeletal Muscle Cells (2008)

Here we report that in skeletal muscle cells the contribution to insulin resistance and inflammation of two common dietary long-chain fatty acids depends on the channeling of these lipids to distinct cellular metabolic fates. Exposure of cells to the saturated fatty acid palmitate led to enhanced diacylglycerol levels and the consequent activation of the protein kinase C/nuclear factor kappaB pathway, finally resulting in enhanced interleukin 6 secretion and down-regulation of the expression of genes involved in the control of the oxidative capacity of skeletal muscle (peroxisome proliferator-activated receptor (PPAR)gamma-coactivator 1alpha) and triglyceride synthesis (acyl-coenzyme A: diacylglycerol acyltransferase 2). In contrast, exposure to the monounsaturated fatty acid oleate did not lead to these changes. Interestingly, co-incubation of cells with palmitate and oleate reversed both inflammation and impairment of insulin signaling by channeling palmitate into triglycerides and by up-regulating the expression of genes involved in mitochondrial beta-oxidation, thus reducing its incorporation into diacylglycerol. Our findings support a model of cellular lipid metabolism in which oleate protects against palmitate-induced inflammation and insulin resistance in skeletal muscle cells by promoting triglyceride accumulation and mitochondrial beta-oxidation through PPARalpha- and protein kinase A-dependent mechanisms.
Gut microbiome influences efficacy of PD-1–based immunotherapy against epithelial tumors (2017)

Immune checkpoint inhibitors (ICIs) targeting the PD-1/PD-L1 axis induce sustained clinical responses in a sizable minority of cancer patients. We found that primary resistance to ICIs can be attributed to abnormal gut microbiome composition. Antibiotics inhibited the clinical benefit of ICIs in patients with advanced cancer. Fecal microbiota transplantation (FMT) from cancer patients who responded to ICIs into germ-free or antibiotic-treated mice ameliorated the antitumor effects of PD-1 blockade, whereas FMT from nonresponding patients failed to do so. Metagenomics of patient stool samples at diagnosis revealed correlations between clinical responses to ICIs and the relative abundance of <i>Akkermansia muciniphila</i> Oral supplementation with <i>A. muciniphila</i> after FMT with nonresponder feces restored the efficacy of PD-1 blockade in an interleukin-12-dependent manner by increasing the recruitment of CCR9<sup>+</sup>CXCR3<sup>+</sup>CD4<sup>+</sup> T lymphocytes into mouse tumor beds.
High-Throughput Method for N-Terminal Sequencing of Proteins by MALDI Mass Spectrometry (2004)

A high-throughput method for sequencing of N termini of proteins by using postsource decay (PSD) of matrix-assisted laser desorption/ionization mass spectrometry has been developed. After a protein blotted on the PVDF membrane was successively reduced, S-alkylated, and guanidinated, its N-amino group was coupled to biotinylcysteic acid. The protein was then extracted from the membrane and digested with trypsin. The derivatized N-terminal fragment was then specifically isolated from the tryptic digest with avidin resins, and its de novo sequencing was successfully performed by PSD utilizing a sulfonic acid group introduced to the N terminus.
Treatment of acromegaly with octreotide‐LAR: extensive experience in a Brazilian institution (2005)

OCT-LAR is an effective agent in alleviating symptoms, suppressing GH, normalizing IGF-I and inducing tumour shrinkage in many acromegalic patients. Overall, OCT-LAR is well tolerated and should be recommended for nonsurgically cured acromegalics, and also be considered as primary therapy for selected cases, mainly for those with a low probability of surgical cure.
Intracerebral electrode implantation system (1983)

A new technique for deep-brain electrode implantation is described. A very flexible nontraumatic electrode guided by a central stylet and a new electrode head-fixation screw are the two unique features of this system. Electrodes can be guided precisely and their watertight fixation to the bone by means of the special screw is reliable and totally reversible. The system has been designed to fit most of the stereotaxic frames currently in use.
The Radius of Gyration of an Apomyoglobin Folding Intermediate (1995)

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Design of Benzamidine-Type Inhibitors of Factor Xa (1998)

A series of derivatives of rac-benzenesulfonyl-glycyl-phenylalanine or its ethyl ester with a combination of thioamido/amidino or amidino/amidino substituents in the benzene rings was synthesized as potential inhibitors of factor Xa (fXa). Among these, the racemic 4'-amidinobenzenesulfonyl-glycyl-4-amidinophenylalanine ethyl ester was found to exhibit the highest affinity for fXa despite the unfavored location of the amidino substituent in the para position. X-ray structural analysis of the trypsin complex with this bis-benzamidine compound revealed a retro-binding mode if compared to those of similar compounds, so far analyzed in complexes with trypsin or fXa. This noncanonical binding mode as well as its slow plasma clearance rates in rats, if compared to those of other benzamidine derivatives, suggests this compound as an interesting new lead structure for the design of fXa inhibitors.