gebhart/patrepeval huggingface dataset:
Selective N-terminal functionalization of native peptides and proteins (2017)

We report an efficient, highly selective modification on the N-terminal amines of peptides and proteins using aldehyde derivatives <i>via</i> reductive alkylation. After modification of a library of unprotected peptides XYSKEASAL (X varies over 20 natural amino acids) by benzaldehyde at room temperature, pH 6.1 resulted in excellent N-terminal selectivity (α-amino/ε-amino: >99 : 1) and high reaction conversion for 19 out of the 20 peptides. Under similar conditions, highly selective N-terminal modifications were achieved with a variety of aldehydes. Furthermore, N-termini of native peptides and proteins could be selectively modified under the same conditions to introduce bioorthogonal functional groups. Using human insulin as an example, we further demonstrated that preserving the positive charge in the N-terminus using reductive alkylation instead of acylation leads to a 5-fold increase in bioactivity. In summary, our reported method provides a universal strategy for site-selective N-terminal functionalization in native peptides and proteins.
The Synthesis of the Mono- and Dihydroxy Derivatives of 1,2,5,6-Dibenzanthracene Excreted by the Rabbit and of Other Hydroxylated Dibenzanthracene Derivatives1 (1958)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTThe Synthesis of the Mono- and Dihydroxy Derivatives of 1,2,5,6-Dibenzanthracene Excreted by the Rabbit and of Other Hydroxylated Dibenzanthracene Derivatives1John A. LaBudde and Charles HeidelbergerCite this: J. Am. Chem. Soc. 1958, 80, 5, 1225–1236Publication Date (Print):March 1, 1958Publication History Published online1 May 2002Published inissue 1 March 1958https://doi.org/10.1021/ja01538a052Request reuse permissionsArticle Views438Altmetric-Citations16LEARN 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 InReddit PDF (1 MB) Get e-Alertsclose Get e-Alerts
Structure of a Mouse Submaxillary Messenger RNA Encoding Epidermal Growth Factor and Seven Related Proteins (1983)

The structure of the messenger RNA (mRNA) encoding the precursor to mouse submaxillary epidermal growth factor (EGF) was determined from the sequence of a set of overlapping complementary DNA's (cDNA). The mRNA is unexpectedly large, about 4750 nucleotide bases, and predicts the sequence of preproEGF, a protein of 1217 amino acids (133,000 molecular weight). The EGF moiety (53 amino acids) is flanked by polypeptide segments of 976 and 188 amino acids at its amino and carboyxl termini, respectively. The amino terminal segment of the precursor contains seven peptides with sequences that are similar but not identical to EGF.
Schedulability Analysis and Optimal Scheduling of Dual-Arm Cluster Tools With Residency Time Constraint and Activity Time Variation (2011)

With wafer residency time constraint of cluster tools in semiconductor manufacturing, activity time variation can make an originally feasible schedule infeasible. Thus, it is difficult to schedule them and schedulability is a vitally important issue. With bounded activity time variation considered, this paper addresses their real-time scheduling issues and conducts their schedulability analysis. A Petri net (PN) model and a control policy are presented. Based on them, this paper derives closed-form schedulability conditions. If schedulable, an algorithm is developed to obtain an offline periodic schedule. This schedule together with the control policy forms a real-time schedule. It is optimal in terms of cycle time and can be analytically computed, which represents significant advance in this area.
Development of "Iodine Transfer Polymerization" and Its Applications to Telechelically Reactive Polymers. (1992)

ヨウ素化合物は炭素-ヨウ素結合の解離エネルギーが低いためラジカル的に活性で, ラジカル重合反応の過程では連鎖移動反応が関与する結果, ラジカル的連鎖再賦活化機構によるラジカルリビング重合の可能となることを見いだした. これを『ヨウ素移動重合』と称したが, 基本的に次のように総括することができる. 1) 重合系のポリマー分子数は系内に添加するヨウ素化合物分子数で決まる. 2) 分子量分布が狭いものを含め, 自由に調整できる. 3) ブロックポリマーの合成を含む遂次連鎖成長が可能である. 4) 分子末端を占めるヨウ素は反応性に富み, 種々のポリマーのテレキリックな架橋や末端反応性高分子の合成に利用できる. 5) 非対称モノマーでは付加配向性の変化が起こりうる. 6) ラジカル開始法として光 (レーザー) の利用が期待される. これらの知見より分子量が数十万に及ぶ高分子, 例えばフッ素ゴムを分子末端のみで架橋するテレキリックなパーオキサイド架橋法, 熱可塑性ゴムをはじめとする種々のブロックポリマー, 液状末端反応性ポリマーなどの開発が可能となった. 本稿では, このヨウ素移動重合の機構解明の結果と種々の利用について述べる。
4-Phenylpyrrolo[3,4-c]carbazole-1,3(2H,6H)-dione Inhibitors of the Checkpoint Kinase Wee1. Structure−Activity Relationships for Chromophore Modification and Phenyl Ring Substitution (2006)

High-throughput screening has identified a novel class of inhibitors of the checkpoint kinase Wee1, which have potential for use in cancer chemotherapy. These inhibitors are based on a 4-phenylpyrrolo[3,4-c]carbazole-1,3(2H,6H)-dione template and have been shown by X-ray crystallography to bind at the ATP site of the enzyme. An extensive study of the effects of substitution around this template has been carried out, which has identified substituents which lead to improvements in potency and selectivity for Wee1. While retention of the maleimide ring and pendant 4-phenyl group is necessary for potency, replacement of the carbazole nitrogen by oxygen is well tolerated and results in improved Wee1 selectivity against the related checkpoint kinase Chk1. Wee1 potency and selectivity are also enhanced by the incorporation of lipophilic functionality at the 2'-position of the 4-phenyl ring, and Wee1 selectivity against Chk1 is favored by C3-C5 alkyl substitution of the carbazole nitrogen. These studies provide a basis for the design of active analogues of the pyrrolocarbazole lead with improved physical properties.
Effects of Intravenous Polymaltose Iron on Oxidant Stress and Non-Transferrin-Bound Iron in Hemodialysis Patients (2005)

Although ESRD patients have a high prevalence of NTBI in their serum, no correlation could be established between the presence of NTBI and an increased oxidative stress. The slow infusion of maltofer does not promote a significant increase in the plasma concentration of oxidative stress markers. It may therefore be considered as a safe complement to erythropoietin therapy.
ELISPOT Assay for Monitoring Cytotoxic T Lymphocytes (CTL) Activity in Cancer Vaccine Clinical Trials (2012)

The profiling and monitoring of immune responses are key elements in the evaluation of the efficacy and development of new biotherapies, and a number of assays have been introduced for analyzing various immune parameters before, during, and after immunotherapy. The choice of immune assays for a given clinical trial depends on the known or suggested immunomodulating mechanisms associated with the tested therapeutic modality. Cell-mediated cytotoxicity represents a key mechanism in the immune response to various pathogens and tumors. Therefore, the selection of monitoring methods for the appropriate assessment of cell-mediated cytotoxicity is thought to be crucial. Assays that can detect both cytotoxic T lymphocytes (CTL) frequency and function, such as the IFN-γ enzyme-linked immunospot assay (ELISPOT) have gained increasing popularity for monitoring clinical trials and in basic research. Results from various clinical trials, including peptide and whole tumor cell vaccination and cytokine treatment, have shown the suitability of the IFN-γ ELISPOT assay for monitoring T cell responses. However, the Granzyme B ELISPOT assay and Perforin ELISPOT assay may represent a more direct analysis of cell-mediated cytotoxicity as compared to the IFN-γ ELISPOT, since Granzyme B and perforin are the key mediators of target cell death via the granule-mediated pathway. In this review we analyze our own data and the data reported by others with regard to the application of various modifications of ELISPOT assays for monitoring CTL activity in clinical vaccine trials.
A murine monoclonal antibody that completely blocks the binding of fibrinogen to platelets produces a thrombasthenic-like state in normal platelets and binds to glycoproteins IIb and/or IIIa. (1983)

To define better the role of the fibrinogen receptor in platelet physiology and to characterize it biochemically, a murine monoclonal antibody that completely blocks the binding of fibrinogen to the platelet surface was produced by the hybridoma technique with the aid of a functional screening assay. Purified F(ab')2 fragments and/or intact antibody completely blocked aggregation induced by ADP, thrombin, or epinephrine and the binding of radiolabeled fibrinogen to platelets induced by ADP. The antibody did not block agglutination of formaldehyde-fixed platelets by ristocetin or shape change induced by either ADP or thrombin. ADP- and epinephrine-induced release of ATP was completely inhibited by the antibody, but inhibition of release induced by collagen and thrombin was dose dependent and partial. The antibody also dramatically inhibited platelet retention in glass-bead columns, platelet adhesion to glass, and clot retraction. Thus, the antibody induced a thrombasthenic-like state. Immunofluorescent studies confirmed the specificity of the antibody for normal platelets and megakaryocytes and suggested that there is a marked decrease in detectable antigen in thrombasthenic platelets. Radiolabeled antibody bound to an average of approximately 40,000 sites on normal platelets but it bound to less than 2,000 sites on the platelets of a patient with thrombasthenia. The antibody immunoprecipitated both glycoproteins IIb and IIIa, and both glycoproteins bound to an affinity column of the antibody. These studies indicate that there is probably a single anatomic site that is crucial to the binding of all fibrinogen molecules and that this site is most likely on the glycoprotein IIb/IIIa complex. It also suggests that the thrombasthenic phenotype can be completely accounted for on the basis of the inhibition of fibrinogen binding to platelets.
The minCD locus of Bacillus subtilis lacks the minE determinant that provides topological specificity to cell division (1993)

A key event of the sporulation process in Bacillus subtilis is the asymmetric cell division that divides the developing cell into two unequal compartments. To examine the function of vegetative cell division genes in this developmental division, we isolated and characterized the B. subtilis counterpart to the Escherichia coli minicell operon minB, which governs correct placement of the division septum. Starting from the closely linked spoIVF locus, we used walking methods to isolate the region of the B. subtilis chromosome proximate to the divIVB minicell locus. DNA sequence analysis found two open reading frames whose predicted products had significant identity to the E. coli MinC cell division inhibitor and the MinD ATPase activator of MinC, and disruption of minCD function generated a minicell phenotype in B. subtilis. Notably, no homologue to the E. coli MinE topological specificity element was found in the B. subtilis minCD region. The B. subtilis min genes were part of an operon transcribed from a major promoter more than 2.5 kb upstream from minC. An internal promoter immediately upstream from minC was dependent on RNA polymerase containing sigma-H and was active at the onset of sporulation. However, neither minC nor minD function was absolutely required for sporulation and, by implication, for asymmetric septum formation.
Legged robots at MIT: what's new since Raibert? (2000)

The MIT Leg Lab is best known for the seminal work of Marc Raibert, who showed in the 1980s that robotic running could be accomplished using a few simple, decoupled control laws. Raibert had shown how to calculate the control effort required for the next step of a run based on the results of the previous step, using simple physics-based rules. But smoothly controlling joints in a continuous-time fashion to effect walking seemed more difficult, particularly for non-stead state conditions. It was unclear how to combine passive dynamics with active control. Other researchers were beginning to address robot walking, and the rich diversity of their approaches was very exciting. It thus seemed that walking was the next important area. We embarked on a two-pronged approach: one focusing on making improvements to electromechanical actuators and robot design, the other on walking algorithms and control.
In Vivo Toxicological Effects of rel A Antisense Phosphorothioates in CD-1 Mice (1994)

To characterize the in vivo toxicity of phosphorothioate antisense oligonucleotides against rel A (p65 subunit of NF-kappa B transcription factor), forty-eight 6-week-old CD-1 mice were split into 4 groups (6/sex/group) receiving vehicle (phosphate-buffered saline) or doses of 50, 100, and 150 mg/kg of rel A antisense oligonucleotides intraperitoneally 3 times weekly for 2 weeks. Clinical signs of toxicity included weakness, and decreased motor activity and food consumption with body weight loss. Mortality occurred in 7 of 12 mice in the 150-mg/kg group and in 2 of 12 mice in the 100-mg/kg group, most of which died within the first 2 to 4 days of treatment. The remaining mice were necropsied on day 15. The major hematological finding was severe dose-dependent thrombocytopenia. The liver enzyme levels were mildly elevated in the serum of mid- and high-dose animals. At necropsy, increased spleen and liver weights were observed in treated mice, some of which also had mild pleural and/or peritoneal effusions. Histopathological examination revealed the likely cause of death to be acute renal failure due to renal cortical or tubular necrosis. Treatment-related changes were also found in the liver, spleen, bone marrow, and several other organs. In summary, the kidney, liver, and bone marrow (megakaryocytic lineage) were identified as the major target organs for toxicity with rel A antisense therapy.
Retinal pigment epithelium cell culture on thin biodegradable poly(DL-lactic-co-glycolic acid) films (1998)

Thin films of 50:50 and 75:25 poly(DL-lactic-co-glycolic acid) (PLGA) were manufactured with a controlled thickness of less than 10 microm. The effect of PLGA copolymer ratio on in vitro cell attachment, proliferation, morphology, and tight junction formation was evaluated using a human D407 retinal pigment epithelium (RPE) cell line. Almost complete cell attachment was achieved on both PLGA films after 8 h of cell seeding, which was comparable to that on tissue culture polystyrene (TCPS) controls. The initial cell seeding density affected attachment, and the optimal value for 50:50 PLGA was 25000 cells cm(-2). After 7 days of in vitro culture, cell density on 50:50 and 75:25 PLGA films increased 45 and 40 folds, respectively, and a 34-fold increase was observed on TCPS. The RPE cells cultured on PLGA films at confluence had a characteristic cobblestone morphology. Confluent RPE cells also developed normal tight junctions in vitro which were concentrated mainly at the apical surfaces of cell-cell junctions. These results demonstrated that thin biodegradable PLGA films can provide suitable substrates for human RPE cell culture, and may serve as temporary carriers for subretinal implantation of organized sheets of RPE.
CVD 908, CVD 908-htrA, and CVD 909 Live Oral Typhoid Vaccines: A Logical Progression (2007)

Typhoid fever remains an important public health problem in many parts of the world. Despite the availability of oral Ty21a (Vivotif; Berna Biotech) and parenteral Vi polysaccharide vaccine (Typhim Vi; Aventis Pasteur), improved typhoid fever vaccines have been sought. These include a series of vaccine candidates developed at the Center for Vaccine Development, University of Maryland, based on attenuation of Salmonella enterica serovar Typhi by deletions in the aroC, aroD, and htrA genes. These vaccine candidates, designated "CVD 908," "CVD 908-htrA," and "CVD 909," have been developed and tested in volunteers with variable success. This review summarizes the clinical data that directed the logical progression of this vaccine development strategy.
Immunization with HIV-1 Gag Protein Conjugated to a TLR7/8 Agonist Results in the Generation of HIV-1 Gag-Specific Th1 and CD8+ T Cell Responses (2005)

One strategy to induce optimal cellular and humoral immune responses following immunization is to use vaccines or adjuvants that target dendritic cells and B cells. Activation of both cell types can be achieved using specific TLR ligands or agonists directed against their cognate receptor. In this study, we compared the ability of the TLR7/8 agonist R-848, which signals only via TLR7 in mice, with CpG oligodeoxynucleotides for their capacity to induce HIV-1 Gag-specific T cell and Ab responses when used as vaccine adjuvants with HIV-1 Gag protein in mice. Injection of R-848 and CpG oligodeoxynucleotides alone enhanced the innate immune responses in vivo as demonstrated by high serum levels of inflammatory cytokines, including IL-12p70 and IFN-alpha, and increased expression of CD80, CD86, and CD40 on CD11c(+) dendritic cells. By contrast, R-848 was a relatively poor adjuvant for inducing primary Th1 or CD8(+) T cell responses when administered with HIV-1 Gag protein. However, when a TLR7/8 agonist structurally and functionally similar to R-848 was conjugated to HIV-1 Gag protein both Th1 and CD8(+) T cells responses were elicited as determined by intracellular cytokine and tetramer staining. Moreover, within the population of HIV-1 Gag-specific CD8(+) CD62(low) cells, approximately 50% of cells expressed CD127, a marker shown to correlate with the capacity to develop into long-term memory cells. Overall, these data provide evidence that TLR7/8 agonists can be effective vaccine adjuvants for eliciting strong primary immune responses with a viral protein in vivo, provided vaccine delivery is optimized.
Fluorine containing C60 derivatives for high-performance electron transporting field-effect transistors and integrated circuits (2008)

We report on electron transporting organic transistors and integrated ring oscillators based on four different solution processible fluorine containing C60 derivatives. Electron mobilities up to 0.15cm2∕Vs are obtained from as-prepared bottom-gate, bottom-contact transistors utilizing gold source-drain electrodes. Despite the high mobility, no long-range structural order could be identified with the semiconductor films exhibiting amorphouslike characteristics. The good electron transport is attributed to the structural symmetry of the fullerene derivatives and the enhanced π-π interactions between C60 units even in the case of amorphouslike films. These advantageous characteristics make fluorine containing C60 derivatives attractive for application in high-performance, large-area organic electronics.
Factor X Deficiency (2009)

Factor X (FX) deficiency is a rare, recessively inherited bleeding disorder representing 10% of all rare bleeding diseases and affecting 1 in every 1,000,000 people. Its clinical presentation places FX deficiency among the most severe of the rare coagulation defects, typically including hemarthroses, hematomas, and umbilical cord, gastrointestinal, and central nervous system bleeding. Phenotype diagnosis is based on the concomitant prolongation of the prothrombin time and activated partial thromboplastin time. Through the measurement of plasma level of FX antigen and its coagulant activity, two main types of deficiency can be distinguished: type I (concomitantly low levels of activity and antigen) and type II (low coagulant activity, but normal or borderline antigen levels). FX protein is mainly synthesized by the liver and is encoded by a gene ( F10) of 27 kb located on chromosome 13, containing 8 exons. One hundred five mutations on F10 have been identified to date, 78% being missense mutations, with no hot-spot regions. There is no specific FX concentrate available, and current treatment includes the administration of fresh-frozen plasma or prothrombin complex concentrates (PCCs) containing FX in addition to other vitamin K-dependent factors. Administration of PCCs is associated with the risk of thromboembolic complication due to the unknown concentrations of other coagulant factors; however, to overcome this problem, a concentrate containing well-defined amounts of FX (and FIX) has recently been developed.
MEASURES AGAINST LEAKAGE AT TUNNEL BOTTOM SLAB CRACKS BY DRAINING PAVEMENT (1998)

Generally for the purpose of minimizing maintenance and repairs and of ensuring higher safety and repairs and better visibility, cement concrete and semi-flexible pavements are used extensively for road section in tunnels. However, the tunnel, which is the subject of the present investigation, inevitably suffers from reflective cracking by differential settlement of the ground or due to other causes and from leakage at the cracks of bottom slabs because it was built on a very weak ground. Under these unfavorable conditions., using a cement concrete pavement might result in early cracking. For this tunnnel, therefore, we investigated a pavement structure which is capable of reducing the occurrence of reflection cracks and of draining water leaking out at the bottom slab cracks. As a result, a mixture, which is used for draining type pavements, was applied for the layer being in contact with the bottom slabs. We confirmed the validity of this method from the result of the follow-up survey of five years.
Taxol (paclitaxel): mechanisms of action. (1994)

Paclitaxel, an antitumor drug that is demonstrating encouraging activity in human malignancies, is likely to play a major role in cancer chemotherapy. Paclitaxel has an unusual chemical structure--it is a complex diterpene having a taxane ring with a four-membered oxetane ring and an ester side chain at position C-13--and a unique mechanism of action. In vitro, paclitaxel enhances the polymerization of tubulin to stable microtubules and also interacts directly with microtubules, stabilizing them against depolymerization by cold and calcium, which readily depolymerize normal microtubules. The fact that the drug has a specific binding site on the microtubule polymer makes it unique among chemotherapeutic agents, and the ability of paclitaxel to polymerize tubulin in the absence of cofactors like guanosine triphosphate and microtubule-associated proteins is unusual. When paclitaxel and microtubule protein are irradiated with ultraviolet light, the drug preferentially binds covalently to the beta-subunit of tubulin. Paclitaxel binds to cells in a specific and saturable manner with a single set of high-affinity binding sites. The microtubule cytoskeleton is reorganized in the presence of paclitaxel and extensive parallel arrays or stable bundles of microtubules are formed in cells growing in tissue culture. Paclitaxel blocks cells in the G2/M phase of the cell cycle and such cells are unable to form a normal mitotic apparatus.(ABSTRACT TRUNCATED AT 250 WORDS)
Progressive Familial Intrahepatic Cholestasis Type 2 in an Indian Child (2017)

Progressive familial intrahepatic cholestasis (PFIC) is a chronic cholestasis syndrome that begins in infancy and usually progresses to cirrhosis within the first decade of life. There are three varieties of PFIC described: PFIC-1 occurs due to mutations in the <i>ATP8B1</i> gene mapped to 18q21.31, PFIC-2 due to mutations in <i>ABCB11</i> mapped to 2q24, and PFIC-3 due to mutations in <i>ABCB4</i> located on 7q21.12. We report an Indian child whose mutation analysis was suggestive of PFIC-2. He underwent a biliary diversion at 3½ years of age but subsequently died secondary to massive hematemesis.