gebhart/patrepeval huggingface dataset:
Analysis of the functions of the first epidermal growth factor-like domain of factor X. (1993)

Upon activation, factor X participates in the prothrombin activation complex. Similar to 4-carboxyglutamic acid (Gla)-domainless protein C, the Gla-domainless factor X (GDFX) contains a high affinity Ca(2+)-binding site critical for the function of these molecules. In the case of protein C, we recently demonstrated that the high affinity Ca(2+)-binding site critical for activation is outside the first epidermal growth factor (EGF) homology domain. To examine if this is also true for factor X, we have expressed in human 293 cells a deletion mutant of factor X (E2FX) which lacks the entire Gla region as well as the NH2-terminal EGF homology region of factor X. Direct binding studies by equilibrium dialysis indicate that E2FX contains a single Ca(2+)-binding site with a dissociation constant (Kd) of 154 +/- 48 microM. The functional properties of E2FX are equivalent or improved over those of GDFX. For instance, the factor X coagulant protein of Russell's viper venom activates E2FX three times faster than recombinant GDFX. Kinetic analysis of prothrombin activation in the absence of membranes indicates that activated GDFX and E2FX bind to factor Va with equal affinity (Kd = 4.1 microM). The Ca2+ concentration required for half-maximal prothrombin activation rates in the above activation system shifted from 721 +/- 113 microM for activated GDFX to 193 +/- 64 microM for activated E2FX. GDFX and E2FX activation rates with the soluble tissue factor-factor VIIa complex were identical as was the Ca2+ dependence of the reaction. We conclude that E2FX retains a high affinity Ca(2+)-binding site and that the first EGF homology domain does not appear to have a positive functional role in the GDFX molecule. However, Ca2+ occupancy of the Ca(2+)-binding site in the first EGF domain of intact factor X may be essential for optimal prothrombin activation.
High-performance ethernet-based communications for future multi-core processors (2007)

Data centers and HPC clusters often incorporate specialized networking fabrics to satisfy system requirements. However, Ethernet's low cost and high performance are causing a shift from specialized fabrics toward standard Ethernet. Although Ethernet's low-level performance approaches that of specialized fabrics, the features that these fabrics provide such as reliable in-order delivery and flow control are implemented, in the case of Ethernet, by endpoint hardware and software. Unfortunately, current Ethernet endpoints are either slow (commodity NICs with generic TCP/IP stacks) or costly (offload engines). To address these issues, the JNIC project developed a novel Ethernet endpoint. JNIC's hardware and software were specifically designed for the requirements of high-performance communications within future data-centers and compute clusters. The architecture combines capabilities already seen in advanced network architectures with new innovations to create a comprehensive solution for scalable and high-performance Ethernet. We envision a JNIC architecture that is suitable for most in-data-center communication needs.
Poly(L-lysine)-graft-dextran copolymer: amazing effects on triplex stabilization under physiological pH and ionic conditions (in vitro) (1998)

Triplex DNA formation involving unmodified triplex-forming oligonucleotides (TFOs) is very unstable under physiological conditions. Here, we report a novel strategy to stabilize both purine and pyrimidine motif triplex DNA within the rat α1 (I) collagen gene promoter under physiologically relevant conditions by a poly(l-lysine)-graft-dextran copolymer. Using an in vitro electrophoretic mobility shift assay, we show that the copolymer almost completely abrogates the inhibitory effects of physiological concentrations of monovalent cations, particularly potassium ion (K+), on purine motif triplex formation involving very low concentrations of an unmodified guanine-rich TFO. Of importance, pH dependency in pyrimidine motif triplex formation involving an unmodified cytosine-rich TFO is also significantly overcome by the copolymer. Finally, the triplex-stabilizing efficiency of the copolymer is remarkably higher than that of other oligocations, like spermine and spermidine. We suggest that the ability of the graft copolymer to stabilize triplex DNA under physiologically relevant pH and salt concentrations will be a cue for further progress in the antigene strategy.
In vitro comparison of two different methods of cell washing (2012)

The storage of red blood cells (RBC) results in increased concentrations of plasma free hemoglobin, potassium, glucose, and lactate, among other undesirable substances. These concentrations continue to increase as RBC products age and can cause deleterious effects to the patient. In the setting of cardiac surgery, the autotransfusion devices are routinely used to wash blood that is shed from the surgical site. These devices could also be used to wash stored RBC units obtained from the blood bank. The objective of this study was to compare the product created by washing a unit of RBCs with the AutoLog autotransfusion device in the operating room to the washed products from a standard cell washer in the blood bank. Eleven outdated RBC units (stored for >42 days at 4 °C) were split in half. One half was washed using the Medtronic AutoLog device; the other half was washed using the blood bank's Cobe 2991 Cell Processor. Analytes were measured on samples from the unwashed parent unit and from the washed daughter units. The parameters measured included hematocrit, free hemoglobin, lactate, lactate dehydrogenase (LDH), potassium, glucose, and pH. When compared to the original untreated RBCs, the glucose, lactate, and potassium levels were decreased when washed in an autotranfusion device. Additionally, the free hemoglobin and LDH levels were significantly lower with the Medtronic Autolog cell saver than in the COBE 2991 Cell Processor. Washing the RBC donor units in an autotransfusion device prior to transfusion can effectively attenuate the increases seen in glucose, potassium, free hemoglobin, and LDH associated with RBC storage lesion.
Europe’s Legitimacy in the Crisis (2015)

Abstract Economic governance and institutional transformation, the focus of the previous two parts of this volume, are not only interdependent but also inextricably intertwined with the legitimacy problématique of the European integration project. The functioning and governance of markets cannot be insulated from social concerns and the claims of citizens, while the functioning of the European Union’s institutional configuration depends on the integrity of these institutions and their trustworthiness in the minds of European citizens. ‘Legitimacy’ is a notion that reminds us of the need to fill the normative and empirical gaps exposed by the first two parts of this volume. This third part seeks, then, to provide an orientation for understanding legitimacy and its erosion, and to explore how legitimacy as an asset may regain strength.
Mechanisms and mediators of nasal symptoms in non‐allergic rhinitis (2008)

Non-allergic rhinitis may be a contributing factor in up to 60% of rhinitis patients and a sole contributor in a quarter. It is a highly heterogeneous condition with poorly understood pathophysiological mechanisms. Compelling evidence is emerging of a localized nasal mucosal allergic response in some non-allergic rhinitic subjects in the absence of systemic atopy. While the inflammatory disease pathway in non-allergic rhinitis may share some of the features of its allergic counterpart, overall the mechanisms remain unclear, and there are likely to be differences. In particular, symptoms of nasal congestion and rhinorrhoea tend to be more prominent and persistent in non-allergic rhinitic patients compared with allergic rhinitis. Our aim is to review the literature relating to mechanisms and mediators of nasal symptoms in non-allergic rhinitis. Better understanding of the underlying pathophysiological basis should enable the development of more accurate testing, and better targeted therapeutic options in the future.
A practical algorithm for constructing oblivious routing schemes (2003)

In a (randomized) oblivious routing scheme the path chosen for a request between a source s and a target t is independent from the current traffic in the network. Hence, such a scheme consists of probability distributions over s-t paths for every source-target pair s,t in the network.In a recent result [11] it was shown that for any undirected network there is an oblivious routing scheme that achieves a polylogarithmic competitive ratio with respect to congestion. Subsequently, Azar et al. [4] gave a polynomial time algorithm that for a given network constructs the best oblivious routing scheme, i.e. the scheme that guarantees the best possible competitive ratio. Unfortunately, the latter result is based on the Ellipsoid algorithm; hence it is unpractical for large networks.In this paper we present a combinatorial algorithm for constructing an oblivious routing scheme that guarantees a competitive ratio of O(log4n) for undirected networks. Furthermore, our approach yields a proof for the existence of an oblivious routing scheme with competitive ratio O(log3n), which is much simpler than the original proof from [11].
Non-Uniform Triple Helical Structure in Chick Skin Type I Collagen on Thermal Denaturation: Raman Spectroscopic Study (1998)

The individual chains in the triple helix of collagen occur in a conformation related to polyproline II because of the presence of large number of imino peptide bonds. However, these residues are not evenly distributed in the collagen molecule which also contains many non-imino residues. These non-imino regions of collagen may be expected to show preference for other than triple helical conformations. The appearance of several Raman bands in solution phase at 65 degrees C raises the possibility of non-uniform triple helical structure in collagen. Raman spectroscopic studies on collagen in the solid state and in solution at a temperature greater than its denaturation temperature, reported here suggest that denatured collagen may exhibit an ensemble of conformational states with yet unknown implications to the biochemical interactions of this important protein component of connective tissues.
Phase I Hepatic Immunotherapy for Metastases Study of Intra-Arterial Chimeric Antigen Receptor–Modified T-cell Therapy for CEA+ Liver Metastases (2015)

We have demonstrated the safety of anti-CEA CAR-T HAIs with encouraging signals of clinical activity in a heavily pretreated population with large tumor burdens. Further clinical testing of CAR-T HAIs for liver metastases is warranted.
The genomic context of natural killer receptor extended gene families (2001)

The two sets of inhibitory and activating natural killer (NK) receptor genes belong either to the Ig or to the C-type lectin superfamilies. Both are extensive and diverse, comprising genes of varying degrees of relatedness, indicative of a process of iterative duplication. We have constructed gene maps to help understand how and when NK receptor genes developed and the nature of their polymorphism. A cluster of over 15 C-type lectin genes, the natural killer complex is located on human chromosome 12p13.1, syntenic with a region in mouse that borders multiple Ly49 loci. The equivalent locus in man is occupied by a single pseudogene, LY49L. The immunoglobulin superfamily of loci, the leukocyte receptor complex (LRC), on chromosome 19q13.4, contains many polymorphic killer cell immunoglobulin-like receptor (KIR) genes as well as multiple related sequences. These include immunoglobulin-like transcript (ILT) (or leukocyte immunoglobulin-like receptor genes), leukocyte-associated inhibitory receptor genes (LAIR), NKp46, Fc alphaR and the platelet glycoprotein receptor VI locus, which encodes a collagen-binding molecule. KIRs are expressed mostly on NK cells and some T cells. The other LRC loci are more widely expressed. Further centromeric of the LRC are sets of additional loci with weak sequence similarity to the KIRs, including the extensive CD66(CEA) and Siglec families. The LRC-syntenic region in mice contains no orthologues of KIRs. Some of the KIR genes are highly polymorphic in terms of sequence as well as for presence/absence of genes on different haplotypes. Some anchor loci, such as KIR2DL4, are present on most haplotypes. A few ILT loci, such as ILT5 and ILT8, are polymorphic, but only ILT6 exhibits presence/absence variation. This knowledge of the genomic organisation of the extensive NK superfamilies underpins efforts to understand the functions of the encoded NK receptor molecules. It leads to the conclusion that the functional homology of human KIR and mouse Ly49 genes arose by convergent evolution. NK receptor immunogenetics has interesting parallels with the major histocompatibility complex (MHC) in which some of the polymorphic genes are ligands for NK molecules. There are hints of an ancient genetic relationship between NK receptor genes and MHC-paralogous regions on chromosomes 1, 9 and 19. The picture that emerges from both complexes is of eternal evolutionary restlessness, presumably in response to resistance to disease.
Activation of the ATM Kinase by Ionizing Radiation and Phosphorylation of p53 (1998)

The p53 tumor suppressor protein is activated and phosphorylated on serine-15 in response to various DNA damaging agents. The gene product mutated in ataxia telangiectasia, ATM, acts upstream of p53 in a signal transduction pathway initiated by ionizing radiation. Immunoprecipitated ATM had intrinsic protein kinase activity and phosphorylated p53 on serine-15 in a manganese-dependent manner. Ionizing radiation, but not ultraviolet radiation, rapidly enhanced this p53-directed kinase activity of endogenous ATM. These observations, along with the fact that phosphorylation of p53 on serine-15 in response to ionizing radiation is reduced in ataxia telangiectasia cells, suggest that ATM is a protein kinase that phosphorylates p53 in vivo.
Pharmacological activities of Genistein, an isoflavone from soy (Glycine max): part II--anti-cholesterol activity, effects on osteoporosis & menopausal symptoms. (2001)

Phytoestrogens represent a family of plant compounds such as isoflavones, flavones and lignans. A wide range of commonly consumed foods contains appreciable amounts of different phytoestrogens such as isoflavones and lignans. Soy and its products are particularly good sources of isoflavones and lignans. The evidence reviewed here represents the beneficial effects of most potential and promising isoflavone, Genistein in various types of diseases such as osteoporosis, cardiovascular diseases, menopausal symptoms by accumulating evidence from molecular and cellular biology experiments, animal studies, and, to a limited extent, human clinical trials. This review suggests that phytoestrogens may potentially confer health benefits related to various diseases such as cardiovascular disorder, menopausal symptoms, and osteoporosis.
Phase III Trial Comparing Carboplatin, Paclitaxel, and Bexarotene With Carboplatin and Paclitaxel in Chemotherapy-Naïve Patients With Advanced or Metastatic Non–Small-Cell Lung Cancer: SPIRIT II (2008)

Although the addition of bexarotene to chemotherapy did not improve survival in the overall study population, occurrence of high-grade hypertriglyceridemia in bexarotene-treated patients strongly correlated with increased survival, suggesting that bexarotene may benefit a segment of first-line NSCLC patients.
Oxcarbazepine in Affective and Schizoaffective Disorders (2001)

Anticonvulsants have been successfully used in pharmacopsychiatry after their therapeutic value in affective and schizoaffective disorders had been documented in several clinical trials. As the authorities in several countries registered newer anticonvulsants with fewer side effects, their therapeutic value in psychiatric disorders was studied. Clinical studies from the early 80's onward have demonstrated the efficacy of oxcarbazepine (OCBZ), a keto derivative of carbamazepine, in treating mania in affective and schizoaffective disorders. In addition, OCBZ has a distinct pharmacokinetic profile concerning drug-drug interactions compared to carbamazepine and other anticonvulsants. Therefore, the value of OCBZ in the treatment of affective and schizoaffective disorders needs to be evaluated. We reviewed the literature with regard to pharmacokinetic and pharmacodynamic characteristics of OCBZ, drug-drug interactions relevant in pharmacopsychiatry, and the clinical effects of OCBZ in the treatment of patients with affective and schizoaffective disorders. According to the literature, OCBZ is regarded as effective in acute mania and appears to reduce the dosage of neuroleptics required for the treatment of affective and schizoaffective disorders. In addition, it has a preferable pharmacokinetic profile with less severe side effects compared to carbamazepine and neuroleptics. Furthermore, since OCBZ does not interact substantially with the cytochrome P450 enzyme system, co-administration with neuroleptics or antidepressants appears to be well tolerated in affective disorders. However, despite promising effects of OCBZ, few clinical studies have been published in the last 15 years. We conclude that further studies should validate the efficacy of OCBZ in treating mania and evaluate possible pharmacopsychiatric indications as well as limitations for this psychotropic compound.
Contribution of Fluorine to Protein−Ligand Affinity in the Binding of Fluoroaromatic Inhibitors to Carbonic Anhydrase II (2000)

Carbonic anhydrase II (CAII) is a zinc metalloenzyme that catalyzes the hydration of CO2 to yield bicarbonate and a proton. N-(4-Sulfamylbenzoyl)benzylamine (SBB) is a tight-binding inhibitor of human CAII with Kd = 2.1 nM. Previous X-ray crystallographic work shows that the benzyl ring of SBB makes an edge-to-face interaction with Phe-131 in the enzyme active site. We have manipulated the electrostatics of this interaction by systematically substituting electronegative fluorine atoms for the benzyl ring hydrogens of SBB. Crystal structures of 10 enzyme−inhibitor complexes have been determined to atomic resolution. Analysis of these structures reveals that the main contributions to enzyme−inhibitor affinity can be approximated by a combination of dipole−induced dipole, dipole−quadrupole, and quadrupole−quadrupole interactions. Surprisingly, different electrostatic components dominate affinity in different enzyme−inhibitor pairs.
Combined use of in situ hybridization and unlabeled antibody peroxidase anti-peroxidase methods: simultaneous detection of type I procollagen mRNAs and factor VIII-related antigen epitopes in keloid tissue. (1991)

In this study, we developed methodology that allows the combined use of in situ hybridization and peroxidase anti-peroxidase techniques on the same tissue section. A human pro alpha 1(I) collagen cDNA and antibodies to factor VIII-related antigen were used on keloid tissue sections as a model for a fibrotic reaction. The basic protocols of the techniques were modified to obtain optimal results. The feasibility of this new method was demonstrated by elucidation of type I procollagen gene expression in the cells of blood vessel wall and the adjacent fibroblasts. In the case of capillaries, pro alpha 1(I) collagen mRNAs were detected within endothelial cells identified by the presence of factor VIII-related antigen. Pro alpha 1(I) collagen mRNAs were also found in close proximity of medium-size blood vessels, but in this context clearly outside the vessel wall. These results may contribute to the understanding of pathogenetic aspects of keloids and other fibrotic conditions. Thus, the combination of in situ hybridization and peroxidase anti-peroxidase techniques provides a useful tool to examine gene expression simultaneously both at mRNA and protein levels in fibrotic tissues. This methodology is also applicable to a variety of other biologic and pathologic situations.
Recombinant human erythropoietin treatment in cisplatin-associated anemia: a randomized, double-blind trial with placebo. (1994)

CDDP-induced anemia is corrected by rHuEPO, which results in reduced blood transfusion requirements.
The Preparation of a Pyrimidine Analog (Isostere) of Promizole and Other Substituted Pyrimidines (1952)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTThe Preparation of a Pyrimidine Analog (Isostere) of Promizole and Other Substituted PyrimidinesWilliam T. Caldwell and A. Nuri SayinCite this: J. Am. Chem. Soc. 1952, 74, 17, 4314–4317Publication Date (Print):September 1, 1952Publication History Published online1 May 2002Published inissue 1 September 1952https://pubs.acs.org/doi/10.1021/ja01137a019https://doi.org/10.1021/ja01137a019research-articleACS PublicationsRequest reuse permissionsArticle Views140Altmetric-Citations7LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
CD15 Expression in Mature Granulocytes Is Determined by α1,3-Fucosyltransferase IX, but in Promyelocytes and Monocytes by α1,3-Fucosyltransferase IV (2001)

The CD15 carbohydrate epitope is expressed in mature human neutrophils, monocytes, and promyelocytes. We aimed to determine the alpha1,3-fucosyltransferase responsible for the expression of CD15 in each subpopulation of leukocytes. Three alpha1,3-fucosyltransferases, FUT4, FUT7, and FUT9, are expressed in human leukocytes. We demonstrated that FUT9 exhibits 20-fold stronger activity for CD15 synthesis than FUT4, whereas FUT4 exhibits 4.5-fold stronger activity for CDw65 synthesis than FUT9. By competitive reverse transcriptase-polymerase chain reaction, FUT9 was found to be strongly expressed in mature granulocytes and peripheral blood mononuclear cell, but not in monocytes. CD34(+) and CD15(+) cells in cord blood and myeloid cell lines (HL-60 and U937) did not express FUT9 at all. FUT4 transcripts were ubiquitously expressed in all blood cells and all cultured cell lines, with HL-60 and U937 cells in particular expressing a number of FUT4 transcripts. Transfection of the FUT9 gene into Jurkat and U937 cells demonstrated that FUT9 has the potential to express CD15 in myeloid and lymphoid cells. These findings suggest that the expression of CD15 in mature granulocytes is directed by FUT9, whereas it is determined in promyelocytes and monocytes by FUT4. Measurement of CD15 synthesizing activity in cell homogenates of each cell population using the polylactosamine acceptor further supported these conclusions.