gebhart/patrepeval huggingface dataset:
beta-Endorphin omission analogs: dissociation of immunoreactivity from other biological activities. (1980)

An analog of human beta-endorphine with omission of four residues at positions 11, 14, 20, and 22 has been synthesized. This analog and other synthetic analogs with deletion of a single amino acid at position 2, 5, 6, 10, 11, 12, 13, 15, or 22 have been assayed for analgesic potency, ileal opiate activity,opiate receptor-binding activity, andimmunoreactivity. Results show that deletion of a single amino acid of the beta-endorphin molecule outside of the enkephalin segment to give des-Gln11-, des-Thr12, des-Pro13-, des-Leu14-, des-Val15-, des-Asn20-, or des-Ile22-beta-endorphin markedly reduced or abolished the immunoreactivity yet gave substantial retention of opiate potencies. Deletion of a single amino acid of beta-endorphin within the enkephalin segment (des-Gly3- or des-Met5-beta-endorphin) did not markedly affect the immunoactivity; however, the opiate activities were abolished or markedly reduced. The data indicate a clear dissociation of immunoactivity from analgesic, ileal-opiate, and opiate receptor-binding activities.
Single Molecule Raman Spectroscopy at the Junctions of Large Ag Nanocrystals (2003)

Molecular surface enhanced Raman scattering (SERS) in compact clusters of 30−70 nm Ag nanocrystals has shown single molecule Raman scattering cross sections that are orders of magnitude larger than free space single molecule luminescence cross sections. We analyze certain aspects of this phenomenon with new numerical electromagnetic calculations, and we also present new spectral depolarization data for single molecule rhodamine 6G scattering. We stress the central role of the Ag femtosecond radiative lifetime, and the spatial distribution of the excited Ag electrons, in the near field and far field optical properties. The fundamental nature of the Ag plasmon excited-electronic-state changes from a volume excitation to a surface junction excitation as two particles approach each other within 1 nm. Adsorbed molecules in the junction interact directly with the metallic excited-state wave function, showing electron-transfer-initiated photochemistry as well as enhanced Raman scattering. Depolarization studies show an uniaxial local electromagnetic symmetry at the junction site. Simultaneous intensity fluctuations in both the R6G molecular lines and the accompanying Ag electronic Raman continuum appear to reflect R6G adsorption−desorption kinetics. We outline the wavelength-dependent properties of a hybrid molecular-metallic wave function as the Raman resonant state.
Successful long-term treatment of systemic lupus erythematosus with rituximab maintenance therapy (2003)

Systemic lupus erythematosus (SLE) is a chronic, inflammatory autoimmune disease that may involve multiple organ systems. Treatment consists of immunosuppression, cytotoxic treatment, plasmapheresis and immunoglobuline therapy. Treatment of patients refractory to standard treatment approaches is difficult and results are poor. We describe a 39-year old patient with SLE suffering from grand mal epilepsy due to cerebral vasculopathy with positive lupus anticoagulant, who was refractory to standard treatment modalities. The patient was treated with the anti-CD20 monoclonal antibody rituximab (375 mg/m2 x 4, repeated at weekly intervals). Rituximab applications were delivered in October 2000, March 2001 and October 2001. Since March 2002 she has received maintenance therapy with rituximab 375 mg/m2 every three months. A second female with refractory SLE was treated successfully in April 2002 and receives maintenance therapy every three months. Both patients responded well to rituximab therapy. The first patient showed a major improvement of her clinical condition, and 30 months after the beginning of the rituximab therapy she is free of any symptoms. Inflammation parameters, ANA and lupus anticoagulant declined significantly after the treatment. The clinical condition of the second patient improved dramatically, all inflammation parameters normalized and her circulating immunocomplexes disappeared. In conclusion, rituximab maintenance treatment may be a new effective therapy in SLE.
Er-Coupled Si Nanocluster Waveguide (2006)

Rib-loaded waveguides containing Er <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">3+</sup> -coupled Si nanoclusters (Si-nc) have been produced to observe optical gain at 1535 nm. The presence of Si-nc strongly improves the efficiency of Er <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">3+ </sup> excitation but may introduce optical loss mechanisms, such as Mie scattering and confined carrier absorption. Losses strongly affect the possibility of obtaining positive optical gain. Si-nc-related losses have been minimized to 1 dB/cm by lowering the annealing time of the Er <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">3+</sup> -doped silicon-rich oxide deposited by reactive magnetron cosputtering. Photoluminescence (PL) and lifetime measurements show that all Er <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">3+</sup> ions are optically active while those that can be excited at high pump rates via Si-nc are only a small percentage. Er <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">3+</sup> absorption cross section is found comparable to that of Er <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">3+</sup> in SiO <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> . However, dependence on the effective refractive index has been found. In pump-probe measurements, it is shown how the detrimental role of confined carrier absorption can be attenuated by reducing the annealing time. A maximum signal enhancement of about 1.34 at 1535 nm was measured
Recombinant interferon alpha and gamma in combination as treatment for metastatic renal cell carcinoma. (1988)

Fifty-three patients with metastatic-renal cell carcinoma received treatment with combinations of recombinant alpha (rIFN-alpha-2a) and gamma (rIFN-gamma) interferons on three different treatment schedules. On treatment schedule A, 13 patients received i.m. rIFN-alpha-2a and rIFN-gamma simultaneously at a 1:1 ratio by dose units (2 X 10(6) U/m2), equivalent to a 1:10 ratio by protein weight. Results included severe constitutional symptoms in 62% of the patients and no partial remissions (PR) or complete remissions among 10 evaluable patients. On treatment schedule B, 25 patients received an i.m. injection of rIFN-alpha-2a and rIFN-gamma simultaneously at a 1:1 ratio by protein weight (2 X 10(6) U/m2 and 2 X 10(5) U/m2, respectively). This schedule was well tolerated, allowing a 25-50% increment in over 75% of the patients. Four patients (16%) achieved PR. On treatment schedule C, 15 patients received alternating weekly therapy: first rIFN-gamma (5 X 10(6) U/m2 daily for 7 days) followed by rIFN-alpha-2a (10 X 10(6) U/m2 daily for 7 days). One of 13 evaluable patients in treatment schedule C achieved an 80% tumor reduction and was rendered free of disease after the primary tumor was resected. Toxicity was similar in nature to that of rIFN-alpha-2a or rIFN-gamma separately. The toxicity of treatment schedule A suggested additive toxic effects. No distinct synergistic antitumor effect was observed.
Percutaneous laser discectomy with the Ho:YAG laser (1992)

A prototype Ho:YAG (2.15 microns) laser operating at 2-J/pulse, 3 Hz through a 600-microns fiber was employed to perform laser discectomies at the L3-4 disc through an 18G needle in five juvenile pigs. No temperature elevations were recorded in the posterior longitudinal ligament at the disc level and all animals recovered fully with no adverse sequelae, even immediately upon awakening from anesthesia. Pathologic examination demonstrated a wide swath of coagulation necrosis confined to the disc space. The Ho:YAG laser, owing to its close approximation to the intense 2.0 microns absorption band of water, appears to be a viable candidate for clinical trials of laser discectomy.
Molecular Insights into Aminoglycoside Action and Resistance (2004)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTMolecular Insights into Aminoglycoside Action and ResistanceSophie Magnet and John S. BlanchardView Author Information Department of Biochemistry, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York 10461 Cite this: Chem. Rev. 2005, 105, 2, 477–498Publication Date (Web):December 8, 2004Publication History Received20 April 2004Published online8 December 2004Published inissue 1 February 2005https://pubs.acs.org/doi/10.1021/cr0301088https://doi.org/10.1021/cr0301088research-articleACS PublicationsCopyright © 2005 American Chemical SocietyRequest reuse permissionsArticle Views5788Altmetric-Citations530LEARN 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 SUBJECTS:Bacteria,Carbohydrates,Genetics,Monomers,Peptides and proteins Get e-Alerts
Intrathecal Injection of the ς1Receptor Antagonist BD1047 Blocks Both Mechanical Allodynia and Increases in Spinal NR1 Expression during the Induction Phase of Rodent Neuropathic Pain (2008)

These results demonstrate that spinal Sig-1Rs play a critical role in both the induction of mechanical allodynia and the activation of spinal N-methyl-d-aspartate receptors in CCI rats and suggest a potential therapeutic role for the use of Sig-1R antagonists in the clinical management of neuropathic pain.
Temperature-responsive bioconjugates. 2. Molecular design for temperature-modulated bioseparations (1993)

We have synthesized carboxyl semitelechelic oligo(N-isopropylacrylamide) (OIPAAm) using radical telomerization with 3-mercaptopropionic acid. This telomerization is also effective for the synthesis of carboxyl semitelechelic co-oligomers of IPAAm with butyl methacrylate (BMA) as hydrophobic or N,N-dimethylacrylamide (DMAAm) as hydrophilic comonomers. All co-oligomers are highly water-soluble at lower temperatures and exhibit phase separation with increasing temperature. Pure OIPAAm exhibits a lower critical solution temperature (LCST) at 32 degrees C, and the LCST for co-oligomers can be controlled to increase over 32 degrees C with increasing DMAAm composition and to decrease below 32 degrees C with increasing BMA composition. OIPAAm was grafted to bovine serum albumin (BSA) and bovine plasma fibrinogen (BPF) by activated ester-amine coupling. These OIPAAm-biomolecule conjugates maintain their temperature responses, are soluble in cold water, and precipitate over a range of temperatures related to oligomer content. Conjugates could be selectively precipitated and independently separated from conjugate solution mixtures with increasing temperature. In this case, the number of OIPAAm molecules attached to a conjugate affects the aggregate sizes of precipitated conjugates in mixtures. Both conjugate mixture ratios and solution concentrations influence the contamination of oligo(IPAAm-co-DMAAm)-BSA conjugates in precipitated oligo(IPAAm-co-BMA)-BPF conjugates. Furthermore, precipitated conjugates separated using centrifugation and filtration redissolve in water and maintain their biofunctionality, indicating the potential of strategy in reversible bioreactors and protein separations.
Use of Drug Combinations in Treatment (1992)

During the last 10 years new approaches for rapid opioid detoxification have included drug combinations such as clonidine and naltrexone to speed and ease the transition from opioid agonist to antagonist maintenance. Other drug combinations include naloxone with midazolam or methohexitone for inpatients, but rapid outpatient methods are more desirable. Clonidine combined with naltrexone enables abrupt opioid withdrawal in 3-5 days in an outpatient/day setting. This approach can be further improved by transition to the partial agonist buprenorphine from either heroin or methadone followed by a 1 day detoxification using naltrexone precipitated withdrawal, ameliorated by clonidine.
High Affinity Binding of Inositol Phosphates and Phosphoinositides to the Pleckstrin Homology Domain of RAC/Protein Kinase B and Their Influence on Kinase Activity (1997)

The influence of inositol phosphates and phosphoinositides on the alpha isoform of the RAC-protein kinase B (RAC/PKB) was studied using purified wild type and mutant kinase preparations and a recombinant pleckstrin homology (PH) domain. Binding of inositol phosphates and phosphoinositides to the PH domain was measured as the quenching of intrinsic tryptophan fluorescence. Inositol phosphates and D3-phosphorylated phosphoinositides bound with affinities of 1-10 microM and 0.5 microM, respectively. Similar values were obtained using RAC/PKB expressed and purified from baculovirus-infected Sf9 cells in the fluorescence assay. The influence of synthetic dioctanoyl derivatives of phosphatidylinositol 3,4-bisphosphate and phosphatidylinositol 3,4,5-trisphosphate on the activity of RAC/PKB purified from transfected COS-1 cells was studied. Phosphatidylinositol 3,4,5-trisphosphate was found to inhibit the RAC/PKB kinase activity with half-maximal inhibition at 2.5 microM. In contrast, phosphatidylinositol 3, 4-bisphosphate stimulated kinase activity (half-maximal stimulation at 2.5 microM). A mutant RAC/PKB protein lacking the PH domain was not affected by D3-phosphorylated phosphoinositides. These results demonstrate that the PH domain of RAC/PKB binds inositol phosphates and phosphoinositides with high affinity, and suggest that the products of the phosphatidylinositide 3-kinase can act as both a membrane anchor and modulator of RAC/PKB activity. The data also provide further evidence for a link between phosphatidylinositide 3-kinase and RAC/PKB regulation.
A Polar Sulfamide Spacer Significantly Enhances the Manufacturability, Stability, and Therapeutic Index of Antibody–Drug Conjugates (2018)

Despite tremendous efforts in the field of targeted cancer therapy with antibody-drug conjugates (ADCs), attrition rates have been high. Historically, the priority in ADC development has been the selection of target, antibody, and toxin, with little focus on the nature of the linker. We show here that a short and polar sulfamide spacer (HydraSpace™, Oss, The Netherlands) positively impacts ADC properties in various ways: (a) efficiency of conjugation; (b) stability; and (c) therapeutic index. Different ADC formats are explored in terms of drug-to-antibody ratios (DAR2, DAR4) and we describe the generation of a DAR4 ADC by site-specific attachment of a bivalent linker-payload construct to a single conjugation site in the antibody. A head-to-head comparison of HydraSpace™-containing DAR4 ADCs to marketed drugs, derived from the same antibody and toxic payload components, indicated a significant improvement in both the efficacy and safety of several vivo models, corroborated by in-depth pharmacokinetic analysis. Taken together, HydraSpace™ technology based on a polar sulfamide spacer provides significant improvement in manufacturability, stability, and ADC design, and is a powerful platform to enable next-generation ADCs with enhanced therapeutic index.
Differential expression of difucosyl type 2 chain (LeY) defined by monoclonal antibody AH6 in different locations of colonic epithelia, various histological types of colonic polyps, and adenocarcinomas. (1986)

The expression of LeY (Fuc alpha 1----2Gal beta 1----4 [Fuc alpha 1----3]GlcNAc beta 1----R) (in which Fuc is fucose, Gal is galactose, and GlcNAc is N-acetylglucosamine) defined by monoclonal antibody AH6 in various locations of human colonic epithelia, colonic polyps, and adenocarcinomas has been studied. In normal colonic mucosa, strong staining by AH6 was observed in the proximal regions such as the terminal ileum and cecum. The staining was, however, greatly reduced in the epithelia of the ascending colon and became very weak in the epithelia of transverse, descending, and sigmoidal colon as well as the rectum. Of 481 crypts in 40 biopsy samples of the epithelia of normal sigmoidal colon, 421 crypts did not show any staining, and only a weak staining of the lowest crypt area was observed in 60 crypts (12%); of 474 crypts in 40 biopsy samples of normal rectal epithelia, 110 crypts (26%) showed a weak staining. At the fetal stage, the LeY staining was much more intense in all locations of the colon than in corresponding locations of adult epithelia, and staining was observed in the epithelia of the sigmoidal colon and rectum. A strong staining was observed in 24 of 25 cases of colorectal adenocarcinomas, irrespective of their original location. The expression of LeY in polyps was correlated with histological type as well as the degree of dysplasia of the polyps. Of various adenomas examined, tubular adenomas, many of which showed mild or moderate dysplasia and less malignant potentials, displayed the least LeY expression. Tubulovillous and villous adenomas, which have higher malignant potential and showed a higher incidence of severe dysplasia, showed a greater area and intensity of LeY expression. No LeY was detectable in juvenile polyps, and only a very weak staining was observed in the dysplastic area of hyperplastic polyps. The extent and intensity of staining in various adenocarcinomas and adenomas could not be correlated with blood group ABO status of the hosts nor with location of the tumors. These results suggest that LeY in colonic adenocarcinomas and polyps at the distal region of the colon and rectum is a typical oncofetal antigen and is a useful marker for diagnosis of colonic cancer. Its expression in colonic polyps can be correlated with the degree of dysplasia and may indicate the degree of malignant potential of the polyp. Thus, LeY expression in polyps may have prognostic value.
Device Layer Transfer Technique using Chemi-Mechanical Polishing (1984)

A device layer transfer technique, a new technique for transferring a thin device layer fabricated on the silicon wafer onto an insulating substrate, is described. The fundamental processes supporting this technique are wafer thinning using chemi-mechanical polishing and wafer fastening. A 2 µm-thick device layer with a 2 inch diameter is formed on a quartz glass substrate without significant degradation in transistor characteristics.
Learning Language in Logic - Genic Interaction Extraction Challenge (2005)

We describe here the context of the LLL challenge of Genic Interaction extraction, the background of its organization and the data sets. We discuss then the results of the participating systems.
Mechanisms of excitotoxicity in neurologic diseases (1992)

Excitotoxicity refers to neuronal cell death caused by activation of excitatory amino acid receptors. A substantial body of evidence has implicated excitotoxicity as a mechanism of cell death in both acute and chronic neurologic diseases. A major recent advance has been the successful cloning and expression of the N-methyl-D-aspartate (NMDA), non-NMDA, and metabotropic glutamate receptors. The cellular mechanisms responsible for cell death after activation of these receptors are still being clarified. In acute neurologic diseases such as stroke and head trauma, excitotoxicity may be related to excessive glutamate release. In chronic neurodegenerative diseases, however, a slow excitotoxic process is more likely to occur as a consequence of either a receptor abnormality or an impairment of energy metabolism. Recent therapeutic studies have demonstrated the efficacy of non-NMDA receptor antagonists in experimental studies of global ischemia.
The complete nucleotide sequence of PEBV RNA2 reveals the presence of a novel open reading frame and provides insights into the structure of tobraviral subgenomic promoters (1990)

The 3374 nucleotide sequence of RNA2 from the British PEBV strain SP5 has been determined. The RNA includes three open reading frames flanked by 5' and 3' noncoding regions of 509 and 480 nucleotides. The open reading frames specify coat protein, a 29.6K product homologous to the 29.1K product of TRV(TCM) RNA2 and a 23K product not homologous to any previously described protein. The homology demonstrated between the coat proteins of PRV, TRV and PEBV indicates a common evolutionary origin for these proteins. Upstream of each ORF are located sequences homologous to those with which subgenomic RNAs of other tobraviruses start. Subgenomic RNAs for the expression of the three ORFs may start at these points. On all five tobraviral RNA2 molecules sequenced to date, these sequences were found upstream of the coat protein ORF in association with a strongly-conserved potential secondary structural element. Similar potential structures were identified upstream of other tobraviral ORFs. These structures may contribute to the activity of the tobraviral subgenomic promoter.
Calcium-dependent protein kinase: widespread occurrence in various tissues and phyla of the animal kingdom and comparison of effects of phospholipid, calmodulin, and trifluoperazine. (1980)

A widespread occurrence of Ca2+-dependent protein kinase was shown in various tissues and phyla of the animal kingdom. Phosphatidylserine appeared to be more effective than calmodulin in supporting the Ca2+-dependent phosphotransferase activity. The phospholipid-sensitive Ca2+-dependent protein kinase activity, distributed in both the cytosolic and particulate fractions, was not inhibited by trifluoperazine, a specific inhibitor of calmodulin-sensitive, Ca2+-dependent reactions or processes. The enzyme activity levels, compared to those of cyclic AMP-dependent and cyclic GMP-dependent protein kinases, were exceedingly high in certain tissues (such as brain and spleen) and exhibited a much greater disparity among tissues. The Ka for Ca2+ was about 100 microM in the presence of phosphatidylserine; the value was as low as 2 microM in the presence of phosphatidylserine and diolein. It is suggested that phospholipid-sensitive Ca2+-dependent protein kinase may mediate certain actions of Ca2+ in tissues, acting independently or in a complementary manner with other protein phosphorylation systems stimulated by calmodulin-Ca2+, cyclic AMP, or cyclic GMP.