gebhart/patrepeval huggingface dataset:
Activation of Raf as a Result of Recruitment to the Plasma Membrane (1994)

The small guanine nucleotide binding protein Ras participates in a growth promoting signal transduction pathway. The mechanism by which interaction of Ras with the protein kinase Raf leads to activation of Raf was studied. Raf was targeted to the plasma membrane by addition of the COOH-terminal localization signals of K-ras. This modified form of Raf (RafCAAX) was activated to the same extent as Raf coexpressed with oncogenic mutant Ras. Plasma membrane localization rather than farnesylation or the presence of the additional COOH-terminal sequence accounted for the activation of RafCAAX. The activation of RafCAAX was completely independent of Ras; it was neither potentiated by oncogenic mutant Ras nor abrogated by dominant negative Ras. Raf, once recruited to the plasma membrane, was not anchored there by Ras; most activated Raf in cells was associated with plasma membrane cytoskeletal elements, not the lipid bilayer. Thus, Ras functions in the activation of Raf by recruiting Raf to the plasma membrane where a separate, Ras-independent, activation of Raf occurs.
Diversity of polyproline recognition by EVH1 domains (2009)

Enabled/VASP Homology-1 (EVH1) domains function primarily as interaction modules that link signaling proteins by binding to proline-rich sequences. EVH1 domains are ~115 residues in length and adopt the pleckstrin homology (PH) fold. Four different protein families contain EVH1 domains: Ena/VASP, Homer, WASP and SPRED. Except for the SPRED domains, for which no binding partners are known, EVH1 domains use a conserved hydrophobic cleft to bind a four-residue motif containing 2-4 prolines. Conserved aromatic residues, including an invariant tryptophan, create a wedge-shaped groove on the EVH1 surface that matches the triangular profile of a polyproline type II helix. Hydrophobic residues adjacent to the polyproline motif dock into complementary sites on the EVH1 domain to enhance ligand binding specificity. Pseudosymmetry in the polyproline type II helix allows peptide ligands to bind in either of two N-to-C terminal orientations, depending on interactions between sequences flanking the prolines and the EVH1 domain. EVH1 domains also recognize non-proline motifs, as illustrated by the structure of an EVH1:LIM3 complex and the extended EVH1 ligands of the verprolin family.
Identification of phenyl-pyridine-2-carboxylic acid derivatives as novel cell cycle inhibitors with increased selectivity for cancer cells (2002)

Ro 41-4439, a phenyl-pyridine-2-carboxylic acid derivative, was identified by a cell-based screening approach that exploits the differences between normal and cancer cells in their sensitivity to cytotoxic agents. This compound showed low micromolar antiproliferative activity and cytotoxicity against a broad panel of human cancer cell lines in vitro, and over 10-fold selectivity to cancer cells when tested in parallel with a panel of proliferating normal human cells. Cytotoxicity of Ro 41-4439 is due to arrest of cell cycle progression in mitosis followed by induction of apoptosis. Four-week treatment of nude mice bearing established mammary tumor xenografts (MDA-MB-435) with well-tolerated doses of the compound showed 73% inhibition of tumor growth. Limited exploration of structure-activity relationships involving side chain length, and aryl and pyridine rings allowed for the identification of more potent analogs.
ULBPs, human ligands of the NKG2D receptor, stimulate tumor immunity with enhancement by IL-15 (2006)

ULBPs are human ligands for NKG2D, an activating receptor expressed on natural killer (NK) cells, NK1.1(+) T cells, and T cells. ULBPs are expressed by a variety of leukemias, carcinomas, melanomas, and tumor cell lines. ULBP expression correlates with improved survival in cancer patients, however, the nature of the immune response that ULBPs elicit is not well understood. We report that ectopic expression of ULBP1 or ULBP2 on murine EL4 or RMA tumor cells elicits potent antitumor responses in syngeneic C57BL/6 and SCID mice. Although binding of ULBP3 to murine NKG2D could not be demonstrated in vitro, ULBP3 can also stimulate antitumor responses, suggesting that ULBP3 binds to murine NKG2D or possibly another receptor in vivo. ULBP expression was found to recruit NK cells, NK1.1(+) T cells, and T cells to the tumor. IL-15 was found to strongly enhance the immune response directed against ULBP-expressing tumors. Tumors can evade NKG2D immunity by down-regulating expression of NKG2D. Our data suggest that IL-15 may be useful for overcoming this tumor-evasion strategy. Together, these results demonstrate that ULBP expression can elicit a potent immune response and suggest that ULBPs, alone or in combination with IL-15, can be exploited for antitumor therapy.
High performance CMOS position-sensitive photodetectors (PSDs) (2002)

Five different constructions of optical position-sensitive detectors (PSDs) implemented using standard CMOS technology are reported. The results show that CMOS technology provides means for implementing high performance PSDs.
Studies of Arginine–Arene Interactions through Synthesis and Evaluation of a Series of Galectin‐Binding Aromatic Lactose Esters (2007)

Aromatic lactose 2-O-esters were synthesized and used to probe arene-arginine interactions with the galectin family of proteins. They were found to be low microM inhibitors of galectin-1, -3, and -9N-terminal domain and moderate inhibitors of galectin-7, but not inhibitors of galectin-8N-terminal, which lacks an arginine residue close to the critical, esterified lactose 2-O-position. Molecular modeling of galectins in complex with aromatic lactose 2-O-esters, as well as binding studies with a galectin-3 R186S mutant, confirmed that the inhibitory efficiency of the lactose 2-O-esters was due to the formation of strong interactions between the aromatic ester moieties and the arginine guanidinium groups of galectin-1 and -3. An important common feature shared by galectin-1 and -3 was that the arginines formed in-plane ion pairs with two side-chain carboxylates, which resulted in extended planar pi-electron surfaces that did not require solvation by water; these surfaces were ideal for stacking with aromatic moieties of the ligands. The results provide a basis for the design of lectin inhibitors and drugs that exploit interactions with arginine side-chains via aromatic moieties, which are involved in intramolecular protein salt bridges.
Flagellar glycosylation – a new component of the motility repertoire? (2006)

The biosynthesis, assembly and regulation of the flagellar apparatus has been the subject of extensive studies over many decades, with considerable attention devoted to the peritrichous flagella of Escherichia coli and Salmonella enterica. The characterization of flagellar systems from many other bacterial species has revealed subtle yet distinct differences in composition, regulation and mode of assembly of this important subcellular structure. Glycosylation of the major structural protein, the flagellin, has been shown most recently to be an important component of numerous flagellar systems in both Archaea and Bacteria, playing either an integral role in assembly or for a number of bacterial pathogens a role in virulence. This review focuses on the structural diversity in flagellar glycosylation systems and demonstrates that as a consequence of the unique assembly processes, the type of glycosidic linkage found on archaeal and bacterial flagellins is distinctive.
Intensive Careof a Collapsed, Anorexic and Pyrexic Dog (2000)

A dog arrives at the practice in a collapsed state having been referred, with a history of anorexia and pyrexia. Stabilising the dog's condition is the first priority and is an area where the nurses take an active role. This case report, which formed part of the author's diploma casebook, charts the dog's progress
Neurotrophic factor therapy for nervous system degenerative diseases (1994)

The ability of neurotrophic factors to regulate developmental neuronal survival and adult nervous system plasticity suggests the use of these molecules to treat neurodegeneration associated with human diseases. Solid rationales exist for the use of NGF and neurotrophin-3 in the treatment of neuropathies of the peripheral sensory system, insulin-like growth factor and ciliary neurotrophic factor in motor neuron atrophy, and NGF in Alzheimer's disease. Growth factors have been identified for neurons affected in Parkinson's disease, Huntington's disease, and acute brain and spinal cord injury. Various strategies are actively pursued to deliver neurotrophic factors to the brain, and develop therapeutically useful molecules that mimic neurotrophic factor actions or stimulate their production or receptor mechanisms.
Can Combination Therapy Overcome Drug Resistance? (1993)

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Ultrasound Imaging of Acute Cardiac Transplant Rejection With Microbubbles Targeted to Intercellular Adhesion Molecule-1 (2003)

Background— Noninvasive techniques for detecting acute cardiac transplant rejection are limited. We hypothesized that ultrasound contrast microbubbles targeted to the endothelial cell (EC) inflammatory marker intercellular adhesion molecule-1 (ICAM-1) would selectively bind to rejecting versus nonrejecting myocardium and that myocardial contrast echocardiography can therefore detect acute rejection. Methods and Results— Lipid-based microbubbles were conjugated to anti-rat ICAM-1 (MB ICAM ) or isotype control antibody (MB Control ). In vitro MB ICAM adhesion to cultured rat ECs, as assessed in a parallel plate flow apparatus, was greater to inflammatory versus normal ECs (11±3 versus 3±2 microbubbles/EC, P &lt;0.005). In vivo abdominal heterotopic heart transplantation was performed in rats (rejection group: Brown Norway to Lewis strain; control group: Lewis to Lewis or Brown Norway to Brown Norway). Triggered myocardial contrast echocardiography was performed during intravenous MB ICAM or MB Control (2.5×10 6 ) injection on postoperative day 5. Myocardial videointensity from adhered MB ICAM was significantly higher in rejecting (n=8) versus control (n=7) rats (10±4 versus 1±4 U, P =0.01). Postmortem histology showed normal myocardium in control rats, whereas allograft myocardium demonstrated grade III to IV rejection and strong immunohistochemical ICAM-1 staining. Conclusions— Preferential adherence of ICAM-1-targeted microbubbles to rejecting versus nonrejecting rat cardiac transplant myocardium can be detected ultrasonically. Targeted microbubbles may thus offer a noninvasive ultrasound imaging technique for the detection of acute cardiac transplant rejection and other processes characterized by endothelial dysfunction.
Variability of response to antiplatelet therapy (2008)

The occurrence of ischaemic events despite aspirin therapy has been called ‘aspirin resistance’ but there is little evidence to support that concept. It has not been established that patients with low levels of response to aspirin treatment on platelet function tests are at increased risk for ischaemic events, and there is no evidence that changing therapy based on test results has any benefit. A subset of patients does appear to be resistant to clopidogrel, which apparently increases their risk for adverse cardiovascular outcomes. Increasing the dose of clopidogrel may improve outcomes. Resistance to newer antiplatelet agents such as prasugrel, cangrelor, and AZD6140 has not been described to date. Low response to glycoprotein (GP) IIb/IIIa inhibitors has been associated with increased incidence of myocardial infarction. Whether platelet function testing should be routinely performed in patients receiving these agents has not been fully assessed.
Dynamic Analysis of Consumer Response to Marketing Strategies (1982)

This paper develops a methodology for modeling consumer response that integrates previous research in stochastic brand selection, diffusion of innovation, test market analysis, and new product design. The methodology makes it practical to extend brand selection models to include diffusion phenomena such as awareness, trial, and information flow. Purchase timing and brand selection are interdependent and both phenomena depend jointly on managerial controls such as advertising, coupons, price-off promotion, product positioning, and consumer characteristics. Within this general structure, we provide practical estimation procedures (a least squares approximation to the maximum likelihood estimates) to determine the parameters which link managerial controls to consumer response. Closed form solutions are derived for cumulative awareness, cumulative trial, penetration, expected sales, and purchases due to promotion—all as a function of time. We also provide simplified expressions for equilibrium (t → ∞) market share. Tradeoffs among complexity of the diffusion process, number of managerial variables, nonstationarity, complexity of purchase timing, consumer segmentation, and sample size are made explicit so that the marketing scientist can customize his analyses to the managerial problems that he faces. The effects of sample size, data interval frequency, and collinearity in the explanatory variables are investigated with simulations based on a five-state consumer response process which depends on 8–10 marketing variables. The paper closes with a brief description of the application and predictive test of a consumer response model based on the methodology.
Identification of the Cystic Fibrosis Gene: Cloning and Characterization of Complementary DNA (1989)

Overlapping complementary DNA clones were isolated from epithelial cell libraries with a genomic DNA segment containing a portion of the putative cystic fibrosis (CF) locus, which is on chromosome 7. Transcripts, approximately 6500 nucleotides in size, were detectable in the tissues affected in patients with CF. The predicted protein consists of two similar motifs, each with (i) a domain having properties consistent with membrane association and (ii) a domain believed to be involved in ATP (adenosine triphosphate) binding. A deletion of three base pairs that results in the omission of a phenylalanine residue at the center of the first predicted nucleotide-binding domain was detected in CF patients.
Trends in Biorobotic Autonomous Undersea Vehicles (2005)

The emergence of biorobotic autonomous undersea vehicle (AUV) as a focus for discipline-integrated research in the context of underwater propulsion and maneuvering is considered within the confines of the Biorobotics Program in the Office of Naval Research. The significant advances in three disciplines, namely the biology-inspired high-lift unsteady hydrodynamics, artificial muscle technology and neuroscience-based control, are discussed in an effort to integrate them into viable products. The understanding of the mechanisms of delayed stall, molecular design of artificial muscles and the neural approaches to the actuation of control surfaces is reviewed in the context of devices based on the pectoral fins of fish, while remaining focused on their integrated implementation in biorobotic AUVs. A mechanistic understanding of the balance between cruising and maneuvering in swimming animals and undersea vehicles is given. All aquatic platforms, in both nature and engineering, except during short duration burst speeds that are observed in a few species, appear to lie within the condition where their natural period of oscillation equals the time taken by them to travel the distance of their own lengths. Progress in the development of small underwater experimental biorobotic vehicles is considered where the three aforementioned disciplines are integrated into one novel maneuvering device or propulsor. The potential in maneuvering and silencing is discussed.
The Clipper processor: instruction set architecture and implementation (1989)

Intergraph's CLIPPER microprocessor is a high performance, three chip module that implements a new instruction set architecture designed for convenient programmability, broad functionality, and easy future expansion.
Characterization of neo-centromeres in marker chromosomes lacking detectable alpha-satellite DNA (1997)

Recent studies have implicated alpha-satellite DNA as an integral part of the centromere, important for the normal segregation of human chromosomes. To explore the relationship between the normal functioning centromere and alpha-satellite DNA, we have studied eight accessory marker chromosomes in which fluorescence in-situ hybridization could detect neither pancentromeric nor chromosome-specific alpha-satellite DNA. These accessory marker chromosomes were present in the majority of or all cells analyzed and appeared mitotically stable, thereby indicating the presence of a functional centromere. FISH analysis with both chromosome-specific libraries and single-copy YACs, together with microsatellite DNA studies, allowed unequivocal identification of both the origin and structure of these chromosomes. All but one of the marker chromosomes were linear mirror image duplications, and they were present along with either two additional normal chromosomes or with one normal and one deleted chromosome. Indirect immunofluorescence analysis revealed that the centromere protein CENP-B was not present on these markers; however, both CENP-C and CENP-E were present at a position defining a 'neo-centromere'. These studies provide insight into a newly defined class of marker chromosomes that lack detectable alpha-satellite DNA. At least for such marker chromosomes, alpha-satellite DNA at levels detectable by FISH appears unnecessary for chromosome segregation or for the association of CENP-C and CENP-E at a functional centromere.
Catalytic Upgrading of Fermentation‐Derived Organic Acids (1999)

The production of organic acids in low-cost, high-efficiency fermentation processes makes available a new route to chemical production from biomass. Because of their multiple functional groups and high reactivity, organic acids can undergo a variety of reactions that are effectively catalyzed by inorganic heterogeneous or homogeneous catalysts. Lactic acid and succinic acid, in particular, are approaching large-scale production via fermentation and show excellent promise as feedstocks for catalytic conversion routes such as hydrogenation, dehydration, or condensation. A number of catalytic conversion pathways of organic acids are potentially competitive with petroleum-based routes in the current economic environment, particularly when integrated into existing biomass/crop processing schemes. This article reviews some of the key reaction pathways available using fermentation-derived organic acids as feedstocks and presents recent results from the authors' lab on succinate hydrogenation to 1,4-butanediol and tetrahydrofuran. By a judicious choice of support properties and reaction conditions, it is possible to achieve yields of either of these two products in excess of 80%.
Unique Single‐Crystalline Beta Carbon Nitride Nanorods (2003)

Growth of single crystal beta carbon nitride ( β ‐C 3 N 4 ) nanorods (see Figure) has been achieved for the first time through thermal annealing of nanosized carbon nitrides induced by high‐energy ball milling under a streaming flow of NH 3 . Most of the nanorods grow along the [001] direction, and the surfaces are defined by (011) and (010) specific crystallographic planes. A possible growth mechanism of the β ‐C 3 N 4 nanorods is discussed.
PROTEOMICS Reviews 2007 (2007)

In this issue of PROTEOMICS you will find the 2007 annual collection of Review articles covering various aspects of proteomics technology and their application in the biosciences.You will recall that in 2006, we had two issues (Volume 6, issues 14 and 20) that contained review articles.These issues were well received which helped us decide to publish a Reviews Issue of PROTEOMICS on an annual basis.We firmly believe that review articles are both an excellent way for the relative newcomer to proteomics to find a way into the literature and for the expert to form an overview of recent major advances in the field. TechnologyIn the area of new and emerging technology, Timothy Veenstra and colleagues discuss issues related to sample preparation for the isolation of protein complexes which remains a critical factor in determining the success of characterisation of protein complexes.Kris Gevaert and colleagues discuss different approaches for (multiplexed) gel-free proteome analysis as applied both for monitoring protein concentration changes and for the study of protein modifications, in particular protein phosphorylation, glycosylation and protein processing.Field-flow fractionation (FFF) methods represent a group of elution separation methods where external force fields act perpendicularly on analytes in a carrier liquid flow with non-uniform velocity profiles.In his review of FFF methods, Josef Chmelik describes selected applications of FFF to protein analysis and discusses future trends in application of FFF to proteomics.The complexity and diversity of tissue samples remains a major challenge in proteomics and Ferdinand von Eggeling and colleagues review the use of laser-based microdissection techniques to overcome this problem and discuss the compatibly of microdissected formalin and cryofixed tissue with different proteomic techniques such as 2-DE, mass spectrometry MS and protein microarrays.Comprehensive collections of specific affinity reagents directed against all human proteins, including splice variants and modifications, will be essential to realisation the ambition to characterise fully the human proteome and this important area is covered in the review by Mike Taussig and coworkers.Phosphorylation is probably the most intensively studied and common posttranslational modification of proteins.In their review, Mark Collins and colleagues addresses recent technological advances in the purification of phosphorylated proteins and peptides and current MS-based strategies used to qualitatively and quantitatively probe these enriched phosphoproteomes.They also describe the application of complementary array-based technologies to derive signalling networks from kinase-substrate interactions and discuss future challenges in the field. BioinformaticsAs proteomic mass spectrometry (MS) has increased in throughput, so has the demand to catalogue the increasing number of peptides and proteins observed by the EDITORIAL
Skin‐Level Gastrostomies and Jejunostomies for Long‐Term Enteral Feeding (1989)

Skin level gastrostomies and jejunostomies were used in 17 patients for long-term enteral feeding. These devices offer greater comfort to the patient and less potential complications and dysfunction compared to tube gastrostomies and jejunostomies. Placement of the skin level devices requires "mature" gastrocutaneous and jejunocutaneous fistulas. These fistulas can be created by initial placement of percutaneous endoscopic gastrostomies and jejunostomies.
Telecommunications applications of ferroelectric liquid-crystal smart pixels (1996)

Ferroelectric liquid crystal over silicon smart pixels offers potential advantages over conventional electronic and waveguide approaches to telecommunications switching. The role of such smart-pixel architectures in space/wavelength optical interconnect and in high-performance ATM switches based on interconnection of optically accessed memory is discussed.