gebhart/patrepeval huggingface dataset:
Solid phase peptide synthesis by oxidation-reduction condensation (1975)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSolid phase peptide synthesis by oxidation-reduction condensationRei Matsueda, Hiroshi Maruyama, Eiichi Kitazawa, Hidekuni Takahagi, and Teruaki MukaiyamaCite this: J. Am. Chem. Soc. 1975, 97, 9, 2573–2575Publication Date (Print):April 1, 1975Publication History Published online1 May 2002Published inissue 1 April 1975https://pubs.acs.org/doi/10.1021/ja00842a062https://doi.org/10.1021/ja00842a062research-articleACS PublicationsRequest reuse permissionsArticle Views181Altmetric-Citations21LEARN 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
Three Generations of Immunoglobulin G Preparations for Clinical Use (1986)

The first purified human immunoglobulin G (IgG) preparation used clinically was immune serum globulin (ISG), which was prepared in the 1940s by E. J. Cohn's group. It was originally formulated in water with 0.3 M glycine at pH 6.8 and was 70%-80% monomeric. ISG was safe when given intramuscularly and efficacious for measles and hepatitis prophylaxis. The next generation of purified IgG began in the 1960s with chemically modified preparations suitable for intravenous administration. The first such IgG intravenous preparation (IGIV) in the United States was IGIV pH 6.8 (Gamimune, Cutter Biological), in which the anticomplement activity found in ISG was removed by reduction and alkylation of disulfide bridges. This product was originally formulated as a 5% IgG solution in water (pH 6.8) with 0.2 M glycine in 10% maltose for stabilization. It remained stable for at least 2.5 years at 5 degrees C, was 80%-90% monomeric, had virtually no anticomplement activity, was safe given intravenously, and was efficacious for prophylaxis in agammaglobulinemic patients. A third generation of purified IgG has since been developed; IGIV pH 4.25, (Gamimune N, Cutter Biological), which was isolated by the Cohn method from human plasma and is safe for intravenous use, is a 5% solution of IgG in water (pH 4.25) with 10% maltose. The product is greater than 99% IgG, greater than 95% monomeric, and has greater than 90% less anticomplement activity than ISG.
Anti-Inflammatory Actions of Neuroprotectin D1/Protectin D1 and Its Natural Stereoisomers: Assignments of Dihydroxy-Containing Docosatrienes (2006)

Protectin D1, neuroprotectin D1 when generated by neural cells, is a member of a new family of bioactive products generated from docosahexaenoic acid. The complete stereochemistry of protectin D1 (10,17S-docosatriene), namely, chirality of the carbon-10 alcohol and geometry of the conjugated triene, required for bioactivity remained to be assigned. To this end, protectin D1/neuroprotectin D1 (PD1) generated by human neutrophils during murine peritonitis and by neural tissues was separated from natural isomers and subjected to liquid chromatography-tandem mass spectrometry and gas chromatography-mass spectrometry. Comparisons with six 10,17-dihydroxydocosatrienes prepared by total organic and biogenic synthesis showed that PD1 from human cells carrying potent bioactivity is 10R,17S-dihydroxy-docosa-4Z,7Z,11E,13E,15Z,19Z-hexaenoic acid. Additional isomers identified included trace amounts of Delta15-trans-PD1 (isomer III), 10S,17S-dihydroxy-docosa-4Z,7Z,11E,13Z,15E,19Z-hexaenoic acid (isomer IV), and a double dioxygenation product 10S,17S-dihydroxy-docosa-4Z,7Z,11E,13Z,15E,19Z-hexaenoic acid (isomer I), present in exudates. 18O2 labeling showed that 10S,17S-diHDHA (isomer I) carried 18O in the carbon-10 position alcohol, indicating sequential lipoxygenation, whereas PD1 formation proceeded via an epoxide. PD1 at 10 nM attenuated (approximately 50%) human neutrophil transmigration, whereas Delta15-trans-PD1 was essentially inactive. PD1 was a potent regulator of polymorphonuclear leukocyte (PMN) infiltration (approximately 40% at 1 ng/mouse) in peritonitis. The rank order at 1- to 10-ng dose was PD1 approximately PD1 methyl ester >> Delta15-trans-PD1 > 10S,17S-diHDHA (isomer I). 10S,17S-dihydroxy-docosa-4Z,7Z,11E,13E,15Z,19Z-hexaenoic acid (isomer VI) proved > or = PD1 in blocking PMN infiltration, but was not a major product of leukocytes. PD1 also reduced PMN infiltration after initiation (2 h) of inflammation and was additive with resolvin E1. These results indicate that PD1 is a potent stereoselective anti-inflammatory molecule.
KLOTHO SUPPLEMENTATION ATTENUATES BLOOD PRESSURE AND CYST GROWTH IN MOUSE POLYCYSTIC KIDNEY DISEASE (2018)

Objective: Klotho interacts with various membrane proteins such as receptors for transforming growth factor (TGF)-beta and insulin-like growth factor (IGF) to alter their function. Renal expression of klotho is diminished in chronic kidney disease. In the present study, the effects of klotho supplementation on polycystic kidney disease (PKD) model were assessed. Design and method: Recombinant human klotho protein (10 μg/kg/day) or vehicle was administered daily by subcutaneous injection to 6 week-old PKD (DBA/2-pcy) mice. Blood pressure was measured by tail-cuff methods. After 2 months, mice were killed by over-dose of anesthesia and the kidneys were harvested for the analysis. Results: Exogenous klotho protein supplementation reduced right (1.24 ± 0.10 vs. 0.84 ± 0.09 g, p < 0.01) and left kidney weight (1.19 ± 0.10 vs. 0.88 ± 0.06 g, p < 0.01), cystic area (51 ± 5 vs. 34 ± 4 %, p < 0.05), systolic blood pressure (110 ± 3 vs. 101 ± 2 mmHg, p < 0.05) and 8-epi-prostaglandin F2alpha excretion (354 ± 86 vs. 100 ± 35 ng/day, p < 0.01) without changes in body weight. Creatinine clearance in klotho-treated PKD mice was higher than the untreated (1.01 ± 0.08 vs. 0.51 ± 0.04 ml/min/g.kidney.wt, p < 0.01). Klotho supplementation reduced plasma angiotensin II levels (459 ± 76 vs 217 ± 31 fmol/ml, p < 0.05) without significant changes in renal angiotensin II concentrations. Exogenous klotho protein supplementation improved renal expression of superoxide dismutase (SOD), as well as renal klotho expression itself (p < 0.01 for each). Klotho supplementation reduced renal expressions of fibronectin and collagen I (p < 0.05 for each), and diminished renal abundance of phosphorylated Akt and mTOR (p < 0.05 for each). Pathological examination revealed that klotho reduced fibrosis index and nuclear staining of Smad3 in PKD kidneys. Conclusions: The present data indicate that klotho supplementation reduces blood pressure in association with ameliorating renin-angiotensin system in PKD mice. Furthermore, our results are consistent with the notion that klotho inhibits IGF signaling, inducing SOD to reduce oxidative stress and suppressing Akt-mTOR signaling to decrease abnormal cystic growth in PKD mice. Finally, the present findings suggest that klotho inhibits TGF-beta signaling through Smad to attenuate fibrosis. The present data provide translational evidence to examine whether klotho supplementation is the treatment of choice for PKD patients resistant to AVP antagonist.
Sensorimotor Transformations in the Posterior Parietal Cortex (2004)

The posterior parietal cortex (PPC) sits at the interface&#13;\nbetween sensory and motor areas and performs sensorimotor transformations.&#13;\nCurrent research is beginning to unravel the details of&#13;\nthis transformation process. The first part of this chapter focuses&#13;\non planning signals found in the PPC. Experiments show that the&#13;\nthought to reach can be read out from the parietal reach region of&#13;\nmonkeys and used to control the position of a computer cursor&#13;\nwithout any reach movements being made by the monkeys. The&#13;\nsecond section reviews recent studies of coordinate tral15formations,&#13;\nwhich are an important aspect of sensorimotor transformations&#13;\nand involve the PPC.
Dose‐dependent effects of the once‐daily GLP‐1 receptor agonist lixisenatide in patients with Type 2 diabetes inadequately controlled with metformin: a randomized, double‐blind, placebo‐controlled trial (2010)

Lixisenatide significantly improved glycaemic control in mildly hyperglycaemic patients with Type 2 diabetes on metformin. Dose-response relationships were seen for once- and twice-daily regimens, with similar efficacy levels, with a 20 microg once-daily dose of lixisenatide demonstrating the best efficacy-to-tolerability ratio. This new, once-daily GLP-1 receptor agonist shows promise in the management of Type 2 diabetes to be defined further by ongoing long-term studies.
RHAMM-R3 peptide vaccination in patients with acute myeloid leukemia, myelodysplastic syndrome, and multiple myeloma elicits immunologic and clinical responses (2007)

The receptor for hyaluronic acid-mediated motility (RHAMM) is an antigen eliciting both humoral and cellular immune responses in patients with acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), and multiple myeloma (MM). We initiated a phase 1 clinical trial vaccinating 10 patients with R3 (ILSLELMKL), a highly immunogenic CD8(+) T-cell epitope peptide derived from RHAMM. In 7 of 10 patients, we detected an increase of CD8(+)/HLA-A2/RHAMM R3 tetramer(+)/CD45RA(+)/CCR7(-)/CD27(-)/CD28(-) effector T cells in accordance with an increase of R3-specific CD8(+) T cells in enzyme linked immunospot (ELISpot) assays. In chromium release assays, a specific lysis of RHAMM-positive leukemic blasts was shown. Three of 6 patients with myeloid disorders (1/3 AML, 2/3 MDS) achieved clinical responses: one patient with AML and one with MDS showed a significant reduction of blasts in the bone marrow after the last vaccination. One patient with MDS no longer needed erythrocyte transfusions after 4 vaccinations. Two of 4 patients with MM showed a reduction of free light chain serum levels. Taken together, RHAMM-R3 peptide vaccination induced both immunologic and clinical responses, and therefore RHAMM constitutes a promising target for further immunotherapeutic approaches. This study is registered at http://ISRCTN.org as ISRCTN32763606 and is registered with EudraCT as 2005-001706-37.
The Impact of Cardiac Natriuretic Peptide Determination on the Diagnosis and Management of Heart Failure (2001)

The long-predicted endocrine function of the heart has been proven by the discovery of atrial natriuretic peptide (atrial natriuretic factor, A-type natriuretic peptide; ANP) 20 years ago. This subsequently led to the description of a whole family of structurally similar but genetically distinct peptides, the natriuretic peptide family, which contributes to cardiovascular homeostasis. These looped peptides promote natriuresis and diuresis, act as vasodilators, and exert antimitogenic effects on cardiovascular tissues. Two members, ANP and brain natriuretic peptide (B-type natriuretic peptide; BNP) are secreted by the heart mainly in response to myocardial stretch induced by volume load. The natriuretic peptides are synthesized as preprohormones. The C-terminal endocrinological active peptides (ANP, BNP) and their N-terminal prohormone fragments are found in plasma. The natriuretic peptide system is activated to its highest degree in ventricular dysfunction. However, natriuretic peptides are increased in all patients with edematous disorders which lead to an increase in atrial tension or central blood volume, such as renal failure or ascitic liver cirrhosis. It could be demonstrated that in chronic heart failure patients and during the subacute phase of myocardial infarction, of all tested neurohormones, the cardiac natriuretic peptides were best markers to identify heart failure and the most powerful predictors of morbidity and mortality. Natriuretic peptides are independent markers for risk assessment. In comparative studies BNP was superior to ANP and its N-terminal prohormone fragments in myocardial infarction as well as in chronic heart failure patients. Less data on N-terminal proBNP (NT-proBNP) is available, but BNP and NT-proBNP appear to be equivalent markers. For primary care physicians natriuretic peptide measurement is useful to decide which patient with suspected heart failure warrants further investigation, particularly when assessment of left ventricular function is not readily available. Natriuretic peptides have an excellent negative predictive value, particularly in high risk patients. An increase in BNP is serious enough to warrant follow-up examinations. For the cardiologists the natriuretic peptides are helpful for guidance of therapy and monitoring disease course in heart failure patients and for risk stratification in heart failure and myocardial infarction.
Phase I Trial of Intraperitoneal Injection of theE1B-55-kd-Gene–Deleted Adenovirus ONYX-015 (dl1520) Given on Days 1 Through 5 Every 3 Weeks in Patients With Recurrent/Refractory Epithelial Ovarian Cancer (2002)

PURPOSE: Resistance to chemotherapy in ovarian cancer is frequently associated with mutations in the p53 gene. The adenovirus dl1520 (ONYX-015) with the E1B 55-kd gene deleted, allowing selective replication in and lysis of p53-deficient tumor cells, has shown preclinical efficacy against p53-deficient nude mouse-human ovarian carcinomatosis xenografts. PATIENTS AND METHODS: We undertook a phase I trial of intraperitoneal dl1520 in patients with recurrent ovarian cancer. Sixteen women with recurrent/refractory ovarian cancer received 35 cycles (median, two cycles) of dl1520 delivered on days 1 through 5 in four dose cohorts: 1 × 10 9 plaque forming units (pfu), 1 × 10 10 pfu, 3 × 10 10 pfu, and 1 × 10 11 pfu. RESULTS: The most common significant toxicities related to virus administration were flu-like symptoms, emesis, and abdominal pain. One patient receiving 1 × 10 10 pfu developed common toxicity criteria grade 3 abdominal pain and diarrhea, which was dose-limiting. The maximum-tolerated dose was not reached at 10 11 pfu, and at this dose level patients did not experience significant toxicity. There was no clear-cut evidence of clinical or radiologic response in any patient. Blood samples were taken for adenovirus DNA and neutralizing antibodies. Polymerase chain reaction data indicating presence of virus up to 10 days after the final (day 5) infusion of dl1520 are suggestive of continuing viral replication. CONCLUSION: This article therefore describes the first clinical experience with the intraperitoneal delivery of any replication-competent/-selective virus in cancer patients.
Knowledge Transfer with Jacobian Matching (2018)

Classical distillation methods transfer representations from a "teacher" neural network to a "student" network by matching their output activations. Recent methods also match the Jacobians, or the gradient of output activations with the input. However, this involves making some ad hoc decisions, in particular, the choice of the loss function. In this paper, we first establish an equivalence between Jacobian matching and distillation with input noise, from which we derive appropriate loss functions for Jacobian matching. We then rely on this analysis to apply Jacobian matching to transfer learning by establishing equivalence of a recent transfer learning procedure to distillation. We then show experimentally on standard image datasets that Jacobian-based penalties improve distillation, robustness to noisy inputs, and transfer learning.
Shielding effect of monovalent and divalent cations on solid-phase DNA hybridization: surface plasmon resonance biosensor study (2010)

Solid-phase hybridization, i.e. the process of recognition between DNA probes immobilized on a solid surface and complementary targets in a solution is a central process in DNA microarray and biosensor technologies. In this work, we investigate the simultaneous effect of monovalent and divalent cations on the hybridization of fully complementary or partly mismatched DNA targets to DNA probes immobilized on the surface of a surface plasmon resonance sensor. Our results demonstrate that the hybridization process is substantially influenced by the cation shielding effect and that this effect differs substantially for solid-phase hybridization, due to the high surface density of negatively charged probes, and hybridization in a solution. In our study divalent magnesium is found to be much more efficient in duplex stabilization than monovalent sodium (15 mM Mg2+ in buffer led to significantly higher hybridization than even 1 M Na+). This trend is opposite to that established for oligonucleotides in a solution. It is also shown that solid-phase duplex destabilization substantially increases with the length of the involved oligonucleotides. Moreover, it is demonstrated that the use of a buffer with the appropriate cation composition can improve the discrimination of complementary and point mismatched DNA targets.
MIF Signal Transduction Initiated by Binding to CD74 (2003)

Macrophage migration inhibitory factor (MIF) accounts for one of the first cytokine activities to have been described, and it has emerged recently to be an important regulator of innate and adaptive immunity. MIF is an upstream activator of monocytes/macrophages, and it is centrally involved in the pathogenesis of septic shock, arthritis, and other inflammatory conditions. The protein is encoded by a unique but highly conserved gene, and X-ray crystallography studies have shown MIF to define a new protein fold and structural superfamily. Although recent work has begun to illuminate the signal transduction pathways activated by MIF, the nature of its membrane receptor has not been known. Using expression cloning and functional analysis, we report herein that CD74, a Type II transmembrane protein, is a high-affinity binding protein for MIF. MIF binds to the extracellular domain of CD74, and CD74 is required for MIF-induced activation of the extracellular signal-regulated kinase-1/2 MAP kinase cascade, cell proliferation, and PGE2 production. A recombinant, soluble form of CD74 binds MIF with a dissociation constant of approximately 9 x 10-9 Kd, as defined by surface plasmon resonance (BIAcore analysis), and soluble CD74 inhibits MIF-mediated extracellular signal-regulated kinase activation in defined cell systems. These data provide a molecular basis for MIF's interaction with target cells and identify it as a natural ligand for CD74, which has been implicated previously in signaling and accessory functions for immune cell activation.
Understanding Atom Transfer Radical Polymerization: Effect of Ligand and Initiator Structures on the Equilibrium Constants (2008)

Equilibrium constants in Cu-based atom transfer radical polymerization (ATRP) were determined for a wide range of ligands and initiators in acetonitrile at 22 degrees C. The ATRP equilibrium constants obtained vary over 7 orders of magnitude and strongly depend on the ligand and initiator structures. The activities of the Cu(I)/ligand complexes are highest for tetradentate ligands, lower for tridentate ligands, and lowest for bidentate ligands. Complexes with tripodal and bridged ligands (Me6TREN and bridged cyclam) tend to be more active than those with the corresponding linear ligands. The equilibrium constants are largest for tertiary alkyl halides and smallest for primary alkyl halides. The activities of alkyl bromides are several times larger than those of the analogous alkyl chlorides. The equilibrium constants are largest for the nitrile derivatives, followed by those for the benzyl derivatives and the corresponding esters. Other equilibrium constants that are not readily measurable were extrapolated from the values for the reference ligands and initiators. Excellent correlations of the equilibrium constants with the Cu(II/I) redox potentials and the carbon-halogen bond dissociation energies were observed.
Identification of the low density lipoprotein receptor-binding site in apolipoprotein B100 and the modulation of its binding activity by the carboxyl terminus in familial defective apo-B100. (1998)

Familial defective apolipoprotein B100 (FDB) is caused by a mutation of apo-B100 (R3500Q) that disrupts the receptor binding of low density lipoproteins (LDL), which leads to hypercholesterolemia and premature atherosclerosis. In this study, mutant forms of human apo-B were expressed in transgenic mice, and the resulting human recombinant LDL were purified and tested for their receptor-binding activity. Site-directed mutagenesis and other evidence indicated that Site B (amino acids 3,359-3,369) binds to the LDL receptor and that arginine-3,500 is not directly involved in receptor binding. The carboxyl-terminal 20% of apo-B100 is necessary for the R3500Q mutation to disrupt receptor binding, since removal of the carboxyl terminus in FDB LDL results in normal receptor-binding activity. Similarly, removal of the carboxyl terminus of apo-B100 on receptor-inactive VLDL dramatically increases apo-B-mediated receptor-binding activity. We propose that the carboxyl terminus normally functions to inhibit the interaction of apo-B100 VLDL with the LDL receptor, but after the conversion of triglyceride-rich VLDL to smaller cholesterol-rich LDL, arginine-3,500 interacts with the carboxyl terminus, permitting normal interaction between LDL and its receptor. Moreover, the loss of arginine at this site destabilizes this interaction, resulting in receptor-binding defective LDL.
Intraoperative Optical Biopsy of Breast Cancer (2007)

Optical coherence tomography (OCT) of breast tissue yields high-resolution optical biopsies that can be used to identify cancerous regions. We present intraoperative OCT studies of surgical margin scanning and biopsy needle guidance.
The Knowledge Weasel hypermedia annotation system (1993)

We describe the organization and implementation of the Knowledge Weasel (KW) Hypermedia Annotation System which we are using to explore knowledge structuring by collaborative annotation.
Methylthioadenosine reverses brain autoimmune disease (2006)

MTA has a remarkable immunomodulatory activity and may be beneficial for multiple sclerosis and other autoimmune diseases.