gebhart/patrepeval huggingface dataset:
Characterization of three abnormal factor IX variants (Bm Lake Elsinore, Long Beach, and Los Angeles) of hemophilia-B. Evidence for defects affecting the latent catalytic site. (1985)

Abnormal factor IX variant proteins were isolated from the plasmas of three unrelated severe hemophilia-B families that had been previously shown to contain functionally impaired molecules immunologically similar to normal factor IX. The families studied were: (1) a patient with markedly prolonged ox brain prothrombin time, designated factor IX Bm Lake Elsinore (IXBmLE); (b) three patients (brothers) with moderately prolonged ox brain prothrombin time, designated factor IX Long Beach (IXLB); and (c) a patient with normal ox brain prothrombin time designated factor IX Los Angeles (IXLA). Each variant molecule comigrates with normal factor IX (IXN) both in the sodium dodecyl sulfate and in the nondenaturing alkaline gel electrophoresis. All three variant proteins are indistinguishable from IXN in their amino acid compositions, isoelectric points, carbohydrate distributions and number of gamma-carboxyglutamic acid residues. Each variant protein undergoes a similar pattern of cleavage by factor XIa/Ca2+ and by factor VIIa/Ca2+/tissue factor, and is activated at a rate similar to that observed for IXN. All of the three variant proteins also react with an anti-IXN monoclonal antibody that interferes with the binding of activated IXN(IXaN) to thrombin-treated factor VIIIC. However, in contrast to IXaN, the cleaved IXBmLE has negligible activity (approximately 0.2%), and cleaved forms of IXLA and IXLB have significantly reduced activity (approximately 5-6%) in binding to antithrombin-III/heparin, and in activating factor VII (plus Ca2+ and phospholipid) or factor X (plus Ca2+ and phospholipid) +/- factor VIII. These data, taken together, strongly indicate that the defect in these three variant proteins resides near or within the latent catalytic site. This results in virtually a complete loss of catalytic activity of the cleaved IXBmLE molecule and approximately 95% loss of catalytic activity of the cleaved IXLA and IXLB molecules.
Oral administration of antibodies as prophylaxis and therapy in Campylobacter jejuni-infected chickens (1997)

Passive immunity against gastrointestinal infections has recently been successfully applied as prophylaxis and therapy in patients in a variety of virally and bacterially induced infections. Campylobacter jejuni is frequently associated with acute diarrhoea in humans, and several species of animals have been shown to transmit the disease, although birds have been implicated as the main source of infection. We used bovine and chicken immunoglobulin preparations from the milk and eggs, respectively, of immunized animals for prophylactic and therapeutic treatment of chickens infected with C. jejuni. A marked prophylactic effect (a >99% decrease in the number of bacteria) was noted using either antibody preparation, whereas the therapeutic efficacy, i.e. when antibodies were given after the infection was established, was distinctly lower (80-95%) as judged by faecal bacterial counts. These observations may serve as a starting point for experiments aimed at elimination of the infection in an industrial or farm setting. It may also encourage future attempts to treat, prophylactically or therapeutically, patients with Campylobacter-induced diarrhoea.
Expression cloning of a human granulocyte colony-stimulating factor receptor: a structural mosaic of hematopoietin receptor, immunoglobulin, and fibronectin domains. (1990)

We report the isolation from a placental library, of two cDNAs that can encode high affinity receptors for granulocyte colony-stimulating factor (G-CSF) when expressed in COS-7 cells. The cDNAs are predicted to encode integral membrane proteins of 759 and 812 amino acids in length. The predicted extracellular and membrane spanning sequences of the two clones are identical, as are the first 96 amino acids of their respective cytoplasmic regions. Different COOH termini of 34 or 87 residues are predicted for the two cDNAs, due apparently to alternate splicing. The receptor with the longer cytoplasmic domain is the closest human homologue of the murine G-CSF receptor recently described by Fukunaga et al. (Fukunaga, R., E. Ishizaka-Ikeda, Y. Seto, and S. Nagata. 1990. Cell. 61:341). A hybridization probe derived from the placental G-CSF receptor cDNA detects a approximately 3-kb transcript in RNAs isolated from placenta and a number of lymphoid and myeloid cells. The extracellular region of the G-CSF receptors is composed of four distinct types of structural domains, previously recognized in other cell surface proteins. In addition to the two domains of the HP receptor family-defining region (Patthy, L. 1990. Cell. 61:13) it incorporates one NH2-terminal Ig-like domain, and three additional repeats of fibronectin type III-like domains. The presence of both an NH2-terminal Ig-like domain and multiple membrane-proximal FN3-like domains suggests that the G-CSF receptor may be derived from an ancestral NCAM-like molecule and that the G-CSF receptor may function in some adhesion or recognition events at the cell surface in addition to the binding of G-CSF.
The Functional Importance of Sympathetic Nerves to the Liver and Endocrine Pancreas (1979)

Sympathetic noradrenergic nerves, with their wellknown cardiovascular effects, have recently been found to influence several metabolic and hormone-releasing processes. Morphological investigations in man have revealed a dense sympathetic innervation of the liver parenchyma as well as sympathetic fibers among the endocrine cells in the islets of Langerhans. Functional studies both in animals and man have shown that electrical or reflex activation of the hepatic and pancreatic sympathetic nerve fibers causes an increased output of glucose from the liver as well as a stimulation of glucagon and an inhibition of insulin release from the pancreas. From these results we conclude that damage to sympathetic nerves should be avoided in abdominal surgery.
A Fullerene−Paclitaxel Chemotherapeutic:  Synthesis, Characterization, and Study of Biological Activity in Tissue Culture (2005)

A fullerene-paclitaxel conjugate has been synthesized as a slow-release drug for aerosol liposome delivery of paclitaxel for lung cancer therapy. The conjugate was designed to release paclitaxel via enzymatic hydrolysis and subsequently has shown a half-life of release of 80 min in bovine plasma. A liposome formulation of the conjugate has been prepared using dilauroylphosphatidylcholine (DLPC), and its IC50 is virtually identical to the IC50 for a paclitaxel-DLPC formulation in human epithelial lung carcinoma A549 cells. With both clinically relevant kinetics of hydrolysis and significant cytotoxicity in tissue culture, the conjugate holds promise for enhanced therapeutic efficacy of paclitaxel in vivo.
Introduction to ground-water tracers. Final report, September 1982-December 1984 (1985)

The general field of ground-water tracers is introduced along with some basic hydrogeologic principles used in planning and conducting tracer tests. The final chapter describes tracer types by category and provides information on specific field techniques, detection limits, laboratory analysis, etc.
Session-based Recommendations with Recurrent Neural Networks (2015)

We apply recurrent neural networks (RNN) on a new domain, namely recommender systems. Real-life recommender systems often face the problem of having to base recommendations only on short session-based data (e.g. a small sportsware website) instead of long user histories (as in the case of Netflix). In this situation the frequently praised matrix factorization approaches are not accurate. This problem is usually overcome in practice by resorting to item-to-item recommendations, i.e. recommending similar items. We argue that by modeling the whole session, more accurate recommendations can be provided. We therefore propose an RNN-based approach for session-based recommendations. Our approach also considers practical aspects of the task and introduces several modifications to classic RNNs such as a ranking loss function that make it more viable for this specific problem. Experimental results on two data-sets show marked improvements over widely used approaches.
Fructan of the inulin neoseries is synthesized in transgenic chicory plants (Cichorium intybus L.) harbouring onion (Allium cepa L.) fructan:fructan 6G‐fructosyltransferase (1997)

Fructan (polyfructosylsucrose) is an important storage carbohydrate in many plant families. fructan:fructan 6G-fructosyltransferase (6G-FFT) is a key enzyme in the formation of the inulin neoseries, a type of fructan accumulated by members of the Liliales. We have cloned the 6G-FFT from onion by screening a cDNA library using barley sucrose:fructan 6-fructosyltransferase (6-SFT) as a probe. The deduced amino acid sequence showed a high homology with plant invertases and 6-SFT. Incubation of protein extracts from transgenic tobacco plants with the trisaccharide 1-kestose and sucrose resulted in the formation of neokestose and fructans of the inulin neoseries with a degree of polymerization up to six. Introduction of the onion 6G-FFT into chicory resulted in the synthesis of fructan of the inulin neoseries, in addition to the synthesis of linear inulin.
Creating an Open Systems Compatible Message Queueing System (2005)

Complex long-lived distributed applications, such as Telecomniunications Provisioning Systems, have been built using the Queued Transaction Processing (QTP) model. Proprietary QTP systems were developed for some of these applications due to the unavailability of commercial systems which could address the requirements of these systems. These QTP systems interconnect various applications running on heterogeneous software and hardware platforms, and have processed large transaction volumes for more than two decades. These applications communicate using structured messages which describe units of work in the QTP system. Vendor-developed Message Queueing Systems are now entering the marketplace. As new systems are developed using vendor solutions, portability and inter-operability among new and existing systems become an issue, especially on platforms where no vendor solutions exist. In this paper, we argue for an Open Systems Compatible Message Queueing System and propose an Open Systems architecture using an asynchronous message-passing facility. This architecture masks choices of operating system from applications as well as masking the more traditional choices of hardware. For complex, long-lived applications, this architecture is a requirement to ensure the success of the application - across both hardware and software platforms updates.
Effects of Peptide YY and Neuropeptide Y on Gastric Emptying in Man (1984)

Neuropeptide Y (NPY) and peptide YY (PYY) are two structurally related peptides. PYY has been identified within endocrine cells and NPY within nerves of the gastrointestinal tract. Infusion of PYY at a low dose at a nominal rate of 2 pmol/kg/min resulted in an increment of 59.2 +/- 7.1 pmol/1 in plasma concentration and a significant delay in gastric emptying of glucose. Infusion of NPY at the same rate produced similar plasma concentrations (52.5 +/- 1.1 pmol/1) and had no significant effect on the rate of gastric emptying.
Identification of the High Affinity Receptor Binding Region in Human Immunoglobulin E (1996)

We have investigated the capacity of N- and C-terminally truncated and chimeric human (h) IgE-derived peptides to inhibit the binding of 125I-labeled hIgE, and to engage cell lines expressing high and low affinity receptors (Fc-epsilon-RI/II). The peptide sequence Pro343-Ser353 of the hC-epsilon-3 domain is common to all h-epsilon-chain peptides that recognize hFc-epsilon-RI. This region in IgE is homologous to the A loop in C-gamma-2 that engages the rat neonatal IgG receptor. Optimum Fc-epsilon-RI occupancy by hIgE occurs at pH 6.4, with a second peak at 7.4. N- or C-terminal truncation has little effect on the association rate of the ligands with this receptor. Dissociation markedly increases following C-terminal deletion, and hFc-epsilon-RI occupancy at pH 6.4 is diminished. His residue(s) in the C-terminal region of the epsilon-chain may thus contribute to the high affinity of interaction. Grafting the homologus rat epsilon-chain sequence into hIgE maintains hFc-epsilon-RI interaction without conferring binding to rat Fc-epsilon-RI. hFc-epsilon-RII interaction is lost, suggesting that these residues also contribute to hFc-epsilon RII binding. h-epsilon-chain peptides comprising only this sequence do not block hIgE/hFc-epsilon-RI interaction or engage the receptor. Therefore, sequences N- or C-terminal to this core peptide provide structures necessary for receptor recognition.
Contractarian Analysis, Ethics, and Emerging Economies (2001)

The transition from socialist to market economics is typically informed by outcomes-based social welfare theory (SWT). Institutionless, intentionally valuefree SWT is ill-suited to this enterprise. The only evaluative standard to which it gives rise—efficiency—is indeterminate, and the theory is not accommodative of other dimensions of moral evaluation. By contrast, the contractarian enterprise focuses on the role and importance of formal and informal institutions, including ethical norms. Given that individuals should be treated as moral equivalents, the project assigns lexical priority to rights and regards justice as impartiality. This explicitly normative, institutional approach permits analysis of potential conflicts between informal norms and prospective, formal rules of the games. Moreover, it underscores the instrumental and intrinsic value of rights in the transition process. Finally, the emphasis on impartiality—embodied in the generality principle—facilitates analysis of constitutional constraints on behavior that is inimical to the transition process. Timothy P. Roth, Contractarian Analysis, Ethics, and Emerging Economies, Journal of Markets & Morality 4, no. 1 (Spring 2001): 55-72
Prediction of Regulatory Interactions from Genome Sequences Using a Biophysical Model for the Arabidopsis LEAFY Transcription Factor (2011)

Despite great advances in sequencing technologies, generating functional information for nonmodel organisms remains a challenge. One solution lies in an improved ability to predict genetic circuits based on primary DNA sequence in combination with detailed knowledge of regulatory proteins that have been characterized in model species. Here, we focus on the LEAFY (LFY) transcription factor, a conserved master regulator of floral development. Starting with biochemical and structural information, we built a biophysical model describing LFY DNA binding specificity in vitro that accurately predicts in vivo LFY binding sites in the Arabidopsis thaliana genome. Applying the model to other plant species, we could follow the evolution of the regulatory relationship between LFY and the AGAMOUS (AG) subfamily of MADS box genes and show that this link predates the divergence between monocots and eudicots. Remarkably, our model succeeds in detecting the connection between LFY and AG homologs despite extensive variation in binding sites. This demonstrates that the cis-element fluidity recently observed in animals also exists in plants, but the challenges it poses can be overcome with predictions grounded in a biophysical model. Therefore, our work opens new avenues to deduce the structure of regulatory networks from mere inspection of genomic sequences.
Sulfated Tyrosines Contribute to the Formation of the C5a Docking Site of the Human C5a Anaphylatoxin Receptor (2001)

The complement anaphylatoxin C5a and its seven-transmembrane segment (7TMS) receptor play an important role in host defense and in a number of inflammation-associated pathologies. The NH(2)-terminal domain of the C5a receptor (C5aR/CD88) contributes substantially to its ability to bind C5a. Here we show that the tyrosines at positions 11 and 14 of the C5aR are posttranslationally modified by the addition of sulfate groups. The sulfate moieties of each of these tyrosines are critical to the ability of the C5aR to bind C5a and to mobilize calcium. A C5aR variant lacking these sulfate moieties efficiently mobilized calcium in response to a small peptide agonist, but not to C5a, consistent with a two-site model of ligand association in which the tyrosine-sulfated region of the C5aR mediates the initial docking interaction. A peptide based on the NH(2) terminus of the C5aR and sulfated at these two tyrosines, but not its unsulfated analogue or a doubly sulfated control peptide, partially inhibited C5a association with its receptor. These observations clarify structural and mutagenic studies of the C5a/C5aR association and suggest that related 7TMS receptors are also modified by functionally important sulfate groups on their NH(2)-terminal tyrosines.
Scalable 3D quantum memory (2018)

Superconducting 3D microwave cavities offer state-of-the-art coherence times and a well controlled environment for superconducting qubits. In order to realize at the same time fast readout and long-lived quantum information storage, one can couple the qubit both to a low-quality readout and a high-quality storage cavity. However, such systems are bulky compared to their less coherent 2D counterparts. A more compact and scalable approach is achieved by making use of the multimode structure of a 3D cavity. In our work, we investigate such a device where a transmon qubit is capacitively coupled to two modes of a single 3D cavity. The external coupling is engineered so that the memory mode has an about 100 times larger quality factor than the readout mode. Using an all-microwave second-order protocol, we realize a lifetime enhancement of the stored state over the qubit lifetime by a factor of $6$ with a $Z$-fidelity of $82\%$. We also find that this enhancement is not limited by fundamental constraints.
Improvements of the electro-optic properties of (Al,Ga)As lasers by means of reduced reflection dielectric facet coatings (1981)

We demonstrate that reduced reflectivity facet coatings of Al2O3 on both mirrors can increase the output power levels at which ’’kinks’’ in the light-current characteristics of proton-delineated 12-μm stripe-geometry (Al,Ga)As lasers occur without causing a significant softening of the ’’turn-on.’’ The dielectric coating is intermediate between half- and quarter-wavelength thicknesses. The advantage of this solution to the kink problem is that it can restore to usefulness lasers which had been previously rejected solely because their kinks occurred just at the power output desired for optical communication application. Although the spontaneous emission output just below threshold is increased somewhat, operation with an extinction ratio equal to 15:1 and reasonable limits on the amplitude of the modulating current is still quite possible. It is also found that reduced reflection coatings can decrease the depth of modulation of self-induced pulsations and decrease the effects of ’’light jumps.’’ The benefits previously connected with half-wavelength coatings should remain unaffected if reduced reflection coatings are deposited instead; such benefits are increased catastrophic-damage thresholds, suppression of light-jump development, suppression of an initially occurring temporally saturable mode of degradation, blocking in-diffusion of degradation-promoting copper, stabilization of self-induced pulsations, and retardation of facet erosion.
Identification of an intracellular receptor for lysophosphatidic acid (LPA): LPA is a transcellular PPARγ agonist (2002)

Lysophosphatidic acid (LPA) is a pluripotent lipid mediator acting through plasma membrane-associated LPA(x) receptors that transduce many, but not all, of its effects. We identify peroxisome proliferator-activated receptor gamma (PPARgamma) as an intracellular receptor for LPA. The transcription factor PPARgamma is activated by several lipid ligands, but agonists derived from physiologic signaling pathways are unknown. We show that LPA, but not its precursor phosphatidic acid, displaces the drug rosiglitazone from the ligand-binding pocket of PPARgamma. LPA and novel LPA analogs we made stimulated expression of a PPAR-responsive element reporter and the endogenous PPARgamma-controlled gene CD36, and induced monocyte lipid accumulation from oxidized low-density lipoprotein via the CD36 scavenger receptor. The synthetic LPA analogs were effective PPARgamma agonists, but were poor ones for LPA(1), LPA(2), or LPA(3) receptor transfected cells. Transfection studies in yeast, which lack nuclear hormone and LPA(x) receptors, show that LPA directly activates PPARgamma. A major growth factor of serum is LPA generated by thrombin-activated platelets, and media from activated platelets stimulated PPARgamma function in transfected RAW264.7 macrophages. This function was suppressed by ectopic LPA-acyltransferase expression. LPA is a physiologic PPARgamma ligand, placing PPARgamma in a signaling pathway, and PPARgamma is the first intracellular receptor identified for LPA. Moreover, LPA produced by stimulated plasma platelets activates PPARgamma in nucleated cells.
Heat production as a quantitative parameter for cell differentiation and cell function. (1990)

Heat production was measured in relation to cell differentiation and phagocytie function using cells of human monocyte-histiocyte cell line U937. U937 cells differentiated monocytic phagocytes when cultured with lymphokine. Heat production increased as result of differentiation and phagocytosis. An important finding was that the heat increase in differentiated cells and during phagocytosis was directly proportional to the concentration of lymphokine. This strongly suggested that heat production is a quantitative parameter not only for cell differentiation but also for phagocytic function. The measurement of heat produced by mammalian cells can therefore be used to quantitate the differentiation and function of cells.
A novel ternary content addressable memory design based on resistive random access memory with high intensity and low search energy (2018)

A novel ternary content addressable memory (TCAM) design based on resistive random access memory (RRAM) is presented. Each TCAM cell consists of two parallel RRAM to both store and search for ternary data. The cell size of the proposed design is 8F2, enable a ∼60× cell area reduction compared with the conventional static random access memory (SRAM) based implementation. Simulation results also show that the search delay and energy consumption of the proposed design at the 64-bit word search are 2 ps and 0.18 fJ/bit/search respectively at 22 nm technology node, where significant improvements are achieved compared to previous works. The desired characteristics of RRAM for implementation of the high performance TCAM search chip are also discussed.
A Spiroligomer α-Helix Mimic That Binds HDM2, Penetrates Human Cells and Stabilizes HDM2 in Cell Culture (2012)

We demonstrate functionalized spiroligomers that mimic the HDM2-bound conformation of the p53 activation domain. Spiroligomers are stereochemically defined, functionalized, spirocyclic monomers coupled through pairs of amide bonds to create spiro-ladder oligomers. Two series of spiroligomers were synthesized, one of structural analogs and one of stereochemical analogs, from which we identified compound 1, that binds HDM2 with a Kd value of 400 nM. The spiroligomer 1 penetrates human liver cancer cells through passive diffusion and in a dose-dependent and time-dependent manner increases the levels of HDM2 more than 30-fold in Huh7 cells in which the p53/HDM2 negative feed-back loop is inoperative. This is a biological effect that is not seen with the HDM2 ligand nutlin-3a. We propose that compound 1 modulates the levels of HDM2 by stabilizing it to proteolysis, allowing it to accumulate in the absence of a p53/HDM2 feedback loop.