gebhart/patrepeval huggingface dataset:
Design and Synthesis of Novel Human Epidermal Growth Factor Receptor 2 (HER2)/Epidermal Growth Factor Receptor (EGFR) Dual Inhibitors Bearing a Pyrrolo[3,2-d]pyrimidine Scaffold (2011)

Dual inhibitors of human epidermal growth factor receptor 2 (HER2) and epidermal growth factor receptor (EGFR) have been investigated for breast, lung, gastric, prostate, and other cancers; one, lapatinib, is currently approved for breast cancer. To develop novel HER2/EGFR dual kinase inhibitors, we designed and synthesized pyrrolo[3,2-d]pyrimidine derivatives capable of fitting into the receptors' ATP binding site. Among the prepared compounds, 34e showed potent HER2 and EGFR (HER1) inhibitory activities as well as tumor growth inhibitory activity. The X-ray cocrystal structures of 34e with both HER2 and EGFR demonstrated that 34e interacts with the expected residues in their respective ATP pockets. Furthermore, reflecting its good oral bioavailability, 34e exhibited potent in vivo efficacy in HER2-overexpressing tumor xenograft models. On the basis of these findings, we report 34e (TAK-285) as a promising candidate for clinical development as a novel HER2/EGFR dual kinase inhibitor.
Peptide Mini-Vectors for Gene Delivery (1999)

The effective treatment of diseases by gene therapy may be a step nearer with the synthesis of two new peptide-based vectors for the delivery of genes to cells. A combination of two peptides—one containing an Arg-Gly-Asp integrin-binding motif, the other a fusogenic moiety—delivers genes almost as effectively as cationic liposomes.
The Compensated Balun (1966)

The compensated balun, first described by Marchand and later reinvented by Roberts, is found to have much broader band-widths than realized by either author. This balun is analyzed here and the parameters which determine its bandwidths are discussed. Curves are presented which allow the design of a balun having any bandwidth. The practical considerations which preclude realization of infinite bandwidths are pointed out. Since the balun is one-quarter wavelength long at center frequency, the balun can be less than one-twentieth wavelength at its lowest operating frequency. Because impedance transformation is generally required with balanced-to-unbalanced line transformation, two techniques including impedance transformation are discused. The reactance slope of the compensated balun is controllable, which allows the balun to directly compensate for the reactance slope of some loads. An example of the compensation of a dipole antenna over a 17-percent bandwidth is discussed. Finally, experimental verification of the balun theory is presented, along with an application to an S-band impedance-transforming compensated balun.
Fluorination of Single-Wall Carbon Nanotubes and Subsequent Derivatization Reactions (2002)

This Account focuses on the most recent and systematic efforts in the area of functionalization chemistry of the single-wall carbon nanotubes (SWNTs) which utilizes direct fluorination for the preparation of "fluoronanonotubes" and their subsequent derivatization. The results obtained prove that the addition of fluorine drastically enhances the reactivity of the nanotube side walls. The use of this strategy as a versatile tool for preparation and manipulation of SWNTs with variable side-wall functionalities has been demonstrated. The functionalized SWNTs have shown an improved solubility in selected solvents and significantly altered electrical, mechanical, and optical properties. An overview of new synthetic methods for preparation and a discussion of characterization data for the functionalized SWNTs are provided.
G‐Quartets 40 Years Later: From 5′‐GMP to Molecular Biology and Supramolecular Chemistry (2004)

Molecular self-assembly is central to many processes in both biology and supramolecular chemistry. The G-quartet, a hydrogen-bonded macrocycle formed by cation-templated assembly of guanosine, was first identified in 1962 as the basis for the aggregation of 5'-guanosine monophosphate. We now know that many nucleosides, oligonucleotides, and synthetic derivatives form a rich array of functional G-quartets. The G-quartet surfaces in areas ranging from structural biology and medicinal chemistry to supramolecular chemistry and nanotechnology. This Review integrates and summarizes knowledge gained from these different areas, with emphasis on G-quartet structure, function, and molecular recognition.
Impact of donor MHC class I or class II antigen deficiency on first‐ and second‐set rejection of mouse heart or liver allografts (1996)

The influence of donor major histocompatibility complex (MHC) class I- or class II-deficiency on the initiation of first- and second-set rejection of mouse heart and liver allografts was examined. C3H (H-2k) mice received heterotopic cardiac or orthotopic liver grafts from unmodified B10 (H-2b), B6 (H-2b), b2m (H-2b; class I deficient) or AB0 (H-2b; class II deficient) donors. Organ survival was also investigated in C3H recipients that had been presensitized by a normal B10 skin graft 2-3 weeks before heart or liver transplantation. The absence of cell surface MHC class I or class II resulted in significant prolongation of primary cardiac allograft survival. Three of seven (43%) MHC class I-deficient, and two of five (40%) class II-deficient heart grafts were accepted indefinitely (survival time > 100 days). Thus both MHC class I and class II molecules appear to be important for the elicitation of first-set rejection in the heart allograft model. All liver allografts survived > 100 days in normal recipients. In C3H recipients that had been presensitized by a B10 skin graft, however, both heart and liver grafts from AB0 (class II deficient) donors underwent accelerated rejection (median survival time [MST] 3 and 4 days, respectively). In contrast, liver grafts from class I-deficient mice (b2m) were still accepted indefinitely by B10 skin-presensitized C3H recipients, whereas class I-deficient hearts survived significantly longer than those from class II-deficient or normal donors. These data demonstrate that the expression of donor MHC class I, and not class II is crucial in initiating second-set organ allograft rejection. In vitro monitoring revealed that at the time of organ transplant, both splenocytes and serum of the skin-presensitized animals displayed high cytotoxicity against AB0 (class II-deficient) but not against b2m (class I-deficient) targets.
A quantitative analysis of lymphokine release from activated T cells. Evidence for a novel form of T-T collaboration in vitro. (1989)

We previously developed a simple mathematical model describing Ag-triggered lymphokine release from activated T cells. Previous test of this model revealed qualitative differences in the antigenic requirement for lymphokine release between activated T cell populations with the same apparent specificity when activated under different conditions. We now have found a case where class I MHC-reactive T cells (class I T cells) can modulate the nature of Ag-triggered lymphokine release from class II MHC-reactive T cells (class II T cells). Two significant requirements for this modulation event are: 1) Linked recognition/presentation of class I and class II Ag; that is, class I and class II MHC alloantigens must be presented on the same APC, and 2) active participation of the APC in this process; metabolic inactivation of the APC abrogates the class I T cell modulation of the class II activated T cell. These results suggest a novel form of T-T collaboration that involves the active participation of the APC, and provides evidence that T cells of one MHC specificity (class I) can influence the function of T cells of another MHC specificity (class II).
Antiretroviral Activity of Emtricitabine, a Potent Nucleoside Reverse Transcriptase Inhibitor (2001)

Several studies have been conducted to determine the relative potency of emtricitabine in human lymphoblastoid T-cell lines (MT-4, CEM, or HT4-6C) acutely infected with a standardized infectious dose of a laboratory-adapted strain of HIV-1 (HIV-1 IIIB or HIV-1 LAV ) or HIV-2 (HIV-2 ZY ) Against laboratoryadapted strains of HIV-1, the EC 50 ranges were 0.009-0.5 M (emtricitabine), 0.005-0.06 M (zidovudine), 0.07-3.2 M (lamivudine), 8.5-16.0 M (didanosine) and 0.03-0.05 M (zalcitabine) (Table Emtricitabine consistently exhibited up to 10-fold greater activity than lamivudine against all viruses tested in all T-cell lines.
Expert determination: a suitable dispute resolution technique for offshore construction project disputes? Part I (2003)

There is a current perception that dispute is an unavoidable feature of any contract for the construction or conversion of offsore units. Allocation of design responsibility amongst several parties, coupled with vessels’ increasing technological complexity and the tight timeframes within which building work must usually be completed, provide fertile ground for disputes to develop. Contracting parties therefore normally make contractual provision for a means of resolving any dispute which might arise. This article, which has been published in two parts, considers the suitability of expert determination – the means by which parties to a contract jointly instruct a third party to decide an issue in a manner not subject to the laws of arbitration – for resolution of the particular types of dispute arisign in offshore construction.
Modification of CD4 Immunoadhesin with Monomethoxypoly(Ethylene Glycol) Aldehyde via Reductive Alkylation (1994)

CD4 immunoadhesin (CD4-IgG) is a chimeric glycoprotein molecule comprised of the gp120-binding portion of human CD4 fused to the hinge and Fc portions of human IgG. As a candidate for human therapeutic use, CD4-IgG represents an important advance over soluble CD4, insofar as the systemic clearance in humans of CD4-IgG is significantly slower. In an effort to prolong its in vivo residence time even further, we have modified CD4-IgG chemically by attaching monomethoxypoly(ethylene glycol) (MePEG) moieties to lysine residues via reductive alkylation. We synthesized MePEG aldehyde and investigated reaction conditions for adding a range of MePEG moieties per protein molecule. At neutral pH in the presence of sodium cyanoborohydride, the reaction was sufficiently slow to allow for significant control over the extent of MePEGylation. Addition of 7.7 or 14.4 MePEG moieties to CD4-IgG resulted in an approximately 4- or 5-fold increase, respectively, in the persistence of the protein in rats, as compared with unmodified CD4-IgG. These results suggest that the therapeutic utility of a human receptor IgG chimera can be improved by MePEGylation technology, provided that the modified immunoadhesin retains its biological activity in vivo. Such modification can lead to a significant additional increase in the in vivo residence time of the protein.
Die Primärstruktur des kristallisierbaren monoklonalen Immunglobulins IgG1Kol. II. Aminosäuresequenz der L-Kette, λ-Typ, Subgruppe I (1989)

Article Die Primärstruktur des kristallisierbaren monoklonalen Immunglobulins IgG1 Kol. II. Aminosäuresequenz der L-Kette, λ-Typ, Subgruppe I was published on January 1, 1989 in the journal Biological Chemistry (volume 370, issue 1).
PROSPECTS FOR PLANT GENOME MODIFICATION BY NONCONVENTIONAL METHODS (1977)

INTRODUCTION 79 UPTAKE OF DNA BY PLANT TISSUES 80 UPTAKE OF DNA BY PLANT CELLS, PROTOPLASTS, AND POLLEN 83 UPTAKE OF PHAGE PARTICLES BY PLANT CELLS AND PROTOPLASTS .... 87 UPTAKE OF ORGANELLES BY PLANT PROTOPLASTS 89 HERITABLE CHANGE OF PLANT PHENOTYPE 91 SOMATIC CELL FUSION 93 CONCLUDING REMARKS 95
Mice Transgenic for Baff Develop Lymphocytic Disorders along with Autoimmune Manifestations (1999)

The cause of many autoimmune and inflammatory diseases is unresolved, although dysregulated production of tumor necrosis factor (TNF) family members appears to be important in many cases. BAFF, a new member of the TNF family, binds to B cells and costimulates their growth in vitro. Mice transgenic for BAFF have vastly increased numbers of mature B and effector T cells, and develop autoimmune-like manifestations such as the presence of high levels of rheumatoid factors, circulating immune complexes, anti-DNA autoantibodies, and immunoglobulin deposition in the kidneys. This phenotype is reminiscent of certain human autoimmune disorders and suggests that dysregulation of BAFF expression may be a critical element in the chain of events leading to autoimmunity.
Nascent helix in the multiphosphorylated peptide αS2‐casein(2–20) (2003)

Sequence-specific nuclear magnetic resonance (NMR) assignments have been determined for the peptide alphaS2-CN(2-20) containing the multiphosphorylated motif-8Ser(P)-Ser(P)-Ser(P)-Glu-Glu12- in the presence of molar excess Ca2+. The secondary structure of the peptide was characterized by sequential (i,i + 1), medium-range (i,i + 2/3/4) nOes and H alpha chemical shifts. Molecular modelling of the peptide based on these constraints suggests a nascent helix for residues Ser(P)9 to Glu12. The spectral data for alphaS2-CN(2-20) were compared with those of other casein phosphopeptides beta-CN(1-25) and alphaS1-CN(59-79) that also contain the multiphosphorylated motif. This comparison revealed a similar pattern of secondary amide chemical shifts in the multiphosphorylated motif. However, the patterns of medium-range nOe connectivities in the three peptides suggests they have distinctly different conformations in the presence of Ca2+ despite having a high degree of sequential similarity.
Trabeculectomy combined with beta irradiation for congenital glaucoma. (1991)

Sixty-six eyes with congenital glaucoma were subjected to trabeculectomy between July 1975 and June 1989 are presented. Thirty-one were treated with beta irradiation at the time of surgery with a strontium-90 applicator; 35 were not treated with beta irradiation. The usual dose was 750 rad. Analysis was limited to three years because of the shorter follow-up of the irradiated eyes. Failure in the two groups was compared statistically. When failure was categorised as IOP greater than 21 mm Hg, beta irradiation was found to be significantly protective with an adjusted risk ratio of 0.31 (95% confidence interval 0.11-0.90, p less than 0.05). Failure categorised as the need for additional medical treatment or further surgery showed significant protection with an adjusted risk ratio of 0.33 (confidence interval 0.12-0.94, p less than 0.05). Multiple regression models were used for the analysis of intraocular pressure; beta irradiation was associated with a significantly lower IOP at six months, one year, and three years (p less than 0.05). Other factors identified as being associated with a reduced failure rate or lower IOP were: no previous topical glaucoma medications: age over seven years; lack of previous surgery involving the conjunctiva. The results indicate that beta irradiation may have a beneficial effect on the prognosis of trabeculectomy in children with congenital glaucoma. However, because of the retrospective and observational nature of the study, the results must be regarded as tentative.
Protein‐bound crotonaldehyde accumulates in the spinal cord of superoxide dismutase‐1 mutation‐associated familial amyotrophic lateral sclerosis and its transgenic mouse model (2007)

Growing evidence documents oxidative stress involvement in ALS. We previously demonstrated accumulation of a protein-bound form of the highly toxic lipid peroxidation product crotonaldehyde (CRA) in the spinal cord of sporadic ALS patients. In the present study, to the determine the role for CRA in the disease processes of superoxide dismutase-1 (SOD1) mutation-associated familial ALS (FALS), we performed immunohistochemical and semi-quantitative cell count analyses of protein-bound CRA (P-CRA) in the spinal cord of SOD1-mutated FALS and its transgenic mouse model. Immunohistochemical analysis revealed increased P-CRA immunoreactivity in the spinal cord of the FALS patients and the transgenic mice compared to their respective controls. In the FALS patients, P-CRA immunoreactivity was localized in almost all of the chromatolytic motor neurons, neurofilamentous conglomerates, spheroids, cordlike swollen axons, reactive astrocytes and microglia, and the surrounding neuropil in the affected areas represented by the anterior horns. In the transgenic mice, P-CRA immunoreactivity was localized in only a few ventral horn glia in the presymptomatic stage, in almost all of the vacuolated motor neurons and cordlike swollen axons and some of the ventral horn reactive astrocytes and microglia in the onset stage, and in many of the ventral horn reactive astrocytes and microglia in the advanced stage. Cell count analysis on mouse spinal cord sections disclosed a statistically significant increase in the density of P-CRA-immunoreactive glia in the ventral horns of the young to old G93A mice compared to the age-matched control mice. The present results indicate that enhanced CRA formation occurs in motor neurons and reactive glia in the spinal cord of SOD1-mutated FALS and its transgenic mouse model as well as sporadic ALS, sug- gesting implications for CRA in the pathomechanism common to these forms of ALS.
End Groups in 1-Butene Polymerization via Methylaluminoxane and Zirconocene Catalyst (1995)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTEnd Groups in 1-Butene Polymerization via Methylaluminoxane and Zirconocene CatalystAlbert Rossi, George Odian, and Jianbin ZhangCite this: Macromolecules 1995, 28, 6, 1739–1749Publication Date (Print):March 1, 1995Publication History Published online1 May 2002Published inissue 1 March 1995https://pubs.acs.org/doi/10.1021/ma00110a003https://doi.org/10.1021/ma00110a003research-articleACS PublicationsRequest reuse permissionsArticle Views276Altmetric-Citations36LEARN 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
mRNA Silencing in Human Erythroid Cell Maturation (2008)

Erythroid precursor cells undergo nuclear extrusion and degradation of mitochondria when they mature to erythrocytes. It has been suggested before that the reticulocyte 15-lipoxygenase (r15-LOX) plays an important role in initiating the breakdown of mitochondria in rabbit reticulocytes. The expression of rabbit r15-LOX is regulated by the heterogeneous nuclear ribonucleoproteins (hnRNP) K and E1 at the translational level. However, this mechanism has never been confirmed in human erythropoiesis. Based on K562 cells we have set up an inducible human erythroid cell system. We show that, during induction, K562 cells exhibit changes in morphology and protein expression that are characteristic for terminal erythroid maturation: nuclear exclusion, expression of endogenous human r15-LOX regulated by hnRNP K and hnRNP E1, and loss of mitochondria. Importantly, induction of terminal erythroid maturation in primary human CD34(+) cells recapitulated the results obtained in K562 cells. Employing the physiologically relevant K562 cell system we uncovered a new mechanism of interdependent post-transcriptional regulation of gene expression. The timely expression of the tyrosine kinase c-Src, which phosphorylates hnRNP K in later stages, is controlled by hnRNP K in early stages of erythroid maturation. hnRNP K binds to the 3'-untranslated region of the c-Src mRNA and inhibits its translation by blocking 80 S ribosome formation. In premature erythroid cells, small interfering RNA-mediated knockdown of hnRNP K, but not of hnRNP E1, leads to the de-repression of c-Src synthesis.
Comparison of the allergenicity of ovalbumin and ovalbumin peptide 323-339. Differential expansion of V beta-expressing T cell populations. (1993)

We analyzed the effects of sensitization of BALB/c mice to the OVA peptide amino acids 323-339, on the development of an IgE response, immediate cutaneous hypersensitivity and airways responsiveness (AR). Daily aerosolization of OVA 323-339 for 20 min over a period of 10 days was as effective in the stimulation of a serum anti-OVA IgE antibody response as sensitization to native OVA by the same route. After sensitization to native OVA, the majority of the IgE anti-OVA response was directed against peptide 323-339. The antibody responses were paralleled by skin test responses in sensitized mice: 73% of OVA-sensitized mice developed immediate type reactions when tested with native OVA and 82% of the mice had positive immediate skin test responses to intradermal injection of peptide 323-339. After sensitization to the peptide, 69% of the mice had positive responses to native OVA and 77% responded to peptide 323-339. Aerosolization of OVA as well as OVA 323-339 led to a comparable increase in airway responsiveness as measured by electrical field stimulation of tracheal smooth muscle preparations. To characterize T cell subpopulations that were stimulated after allergen sensitization, the distribution of specific V beta-expressing T cells was analyzed in local draining lymph nodes of the airways and the lungs. These lymph nodes were found to be enlarged after both OVA and OVA peptide sensitization. Sensitization to native OVA resulted in an increased percentage of V beta 8.1 and V beta 8.2 T cells whereas selective stimulation of V beta 8.1 T cells was found after peptide sensitization. These data indicate that OVA peptide 323-339 represents a T and B cell epitope of OVA, which is important in the generation and development of immediate hypersensitivity responses in BALB/c mice.
Laminin, gamma 2 (LAMC2): A Promising New Putative Pancreatic Cancer Biomarker Identified by Proteomic Analysis of Pancreatic Adenocarcinoma Tissues (2013)

In pancreatic cancer, the incidence and mortality curves coincide. One major reason for this high mortality rate in pancreatic ductal adenocarcinoma (PDAC) patients is the dearth of effective diagnostic, prognostic, and disease-monitoring biomarkers. Unfortunately, existing tumor markers, as well as current imaging modalities, are not sufficiently sensitive and/or specific for early-stage diagnosis. There is, therefore, an urgent need for improved serum markers of the disease. Herein, we performed Orbitrap® mass spectrometry proteomic analysis of four PDAC tissues and their adjacent benign tissues and identified a total of 2190 nonredundant proteins. Sixteen promising candidates were selected for further scrutiny using a systematic scoring algorithm. Our preliminary serum verification of the top four candidates (DSP, LAMC2, GP73, and DSG2) in 20 patients diagnosed with pancreatic cancer and 20 with benign pancreatic cysts, showed a significant (p < 0.05) elevation of LAMC2 in pancreatic cancer serum. Extensive validation of LAMC2 in healthy, benign, and PDAC sera from geographically diverse cohorts (n = 425) (Japan, Europe, and USA) demonstrated a significant increase in levels in early-stage PDAC compared with benign diseases. The sensitivity of LAMC2 was comparable to CA19.9 in all data sets, with an AUC value greater than 0.85 in discriminating healthy patients from early-stage PDAC patients. LAMC2 exhibited diagnostic complementarity with CA19.9 by showing significant (p < 0.001 in two out of three cohorts) elevation in PDAC patients with clinically low CA19.9 levels.