gebhart/patrepeval huggingface dataset:
Synthesis and Structure−Activity Relationships of Novel 7-Substituted 1,4-Dihydro-4-oxo-1-(2-thiazolyl)-1,8-naphthyridine-3-carboxylic Acids as Antitumor Agents. Part 2 (2004)

We have previously reported that a series of 7-substituted 6-fluoro-1,4-dihydro-4-oxo-1-(2-thiazolyl)-1,8-naphthyridine-3-carboxylic acids possess moderate cytotoxic activity. In a further attempt to find clinically useful antitumor agents, we investigated the structure-activity relationships (SARs) of a new series of compounds obtained by changing the C-6 position of the fluorine atom in addition to the C-5 and C-7 positions and evaluating their cytotoxic activity against several murine and human tumor cell lines. Our results showed that the 6-unsubstituted 1,8-naphthyridine structure had the most potent cytotoxic activity against murine P388 leukemia twice that of the 6-fluoro analogue. In addition, introduction of an amino group at the C-5 position did not have any substantial effect on the cytotoxic activity, while both the 5-chloro and 5-trifluoromethyl groups decreased the cytotoxic activity by 5- to 10-fold. Moreover, aminopyrrolidine derivatives at the C-7 position showed more potent cytotoxic activity than other amines or carbon derivatives. Among the 7-(3-aminopyrrolidinyl) derivatives, the trans-3-methoxy-4-methylaminopyrrolidinyl derivative (27l) was determined to have potent cytotoxic activity in both in vitro and in vivo assays and high water solubility. Finally, the (S,S)-isomer (AG-7352, 3) of 27l, with a cytotoxic activity against human tumor cell lines more potent than that of etoposide, was selected for further development.
Janusin: new molecular design for bispecific reagents. (1992)

It is well established that soluble CD4 (sCD4) inhibits HIV infection in vitro, regardless of the virus strain or genetic variant. Most effective molecules, thus far, based on sCD4 are those in which CD4 is combined with immunoglobulin constant regions (CD4-IgG or CD4-IgM). Such molecules maintained HIV-gp120 specificity mediated by CD4 and also antibody effector functions such as complement activation, Fc receptor binding, long serum half-life or transport across the placental barrier. We have now developed sCD4 molecules which are even more potent anti-HIV reagents. These molecules are based on the principle of bispecific antibodies and they have properties capable of retargeting cytotoxic T lymphocytes onto HIV-infected cells and inducing efficient killing. CD4 combined with anti-human CD3 (FvCD3) single-chain combining site has been produced (CD4-FvCD3-JANUSIN). This molecule shows the expected biological activities, namely, binding to the 2 ligands, human CD3 and gp120, also efficiently retargeting CTLs of any specificity onto HIV-infected cells. In addition, several advantages over classical bispecific antibodies can be achieved: only one polypeptide, not a mixture containing the desired product, is produced, thus simplifying the purification process. In addition, Janusin designs do not contain the Ig Fc portion, which could mediate illegitimate retargeting of T-cells. In addition to CD4-FvCD3-JANUSIN, receptor-Fv, Fv-Fv or ligand-Fv Janusins can be produced.
The Green ChemisTREE: 20 years after taking root with the 12 principles (2018)

A broad overview of the achievements and emerging areas in the field of Green Chemistry.
Successful treatment of severe psoriasis with basiliximab, an interleukin-2 receptor monoclonal antibody (2000)

T-cell mediated inflammation plays an important role in the aetiology of psoriasis. We describe a case of severe recalcitrant psoriasis responding well to combined cyclosporin and basiliximab (Simulect(R) Novartis Pharmaceuticals UK Ltd), an interleukin-2 receptor (IL-2R; CD25) chimeric monoclonal antibody.
Novel Strategy of High-Abundance Protein Depletion Using Multidimensional Liquid Chromatography (2006)

In this study, for the first time, a comprehensive two-dimensional (2D) liquid-phase separation system, coupling strong cation exchange chromatography (SCX) to reversed-phase high performance liquid chromatography (RPLC), instead of specificity depletion method, was developed at the intact protein level for depletion of high-abundance proteins from rat liver. Proteins were prefractionated by SCX in the first dimensional separation, followed by RPLC with high resolution separation. UV absorption intensity was used to differentiate high-abundance proteins. The proteins with the absorbance intensity above 0.1 AU were defined as high abundance proteins and depleted. After removal of high-abundance proteins; other proteins were pooled, digested, and subsequently separated by capillary liquid chromatography coupled with MALDI-TOF/TOF mass spectrometry analysis. The high efficiency of the strategy was demonstrated by analyzing the soluble protein extracted from rat liver tissue. In total, 77 high-abundance proteins were depleted in one experiment flow. The ratio of depleted content of high-abundance proteins to that of total proteins was about 34.5%. In total, 1530 proteins were identified using the depletion strategy. Quantitative estimation of high-abundance proteins through liquid chromatography combined with UV absorption spectra was achieved. On the basis of the reproducible experimental results, a rapid and high-throughput depletion protocol was put forward. Along with depletion of the most (79.1%) high-abundance proteins and the separation of digested peptides, the total separation time could be less than 30 h. This strategy has no bias for depleting high-abundance proteins and enhances the number of identified proteins; therefore, it can be widely used in the global proteins analysis.
Near-Infrared Fluorescent Immunoassays: A Novel Approach to Environmental Analysis (1997)

The near-infrared (NIR) region of spectrum provides many advantages over conventional UV-visible region and is particularly useful when background interference is the primary concern. Many NIR fluorophores have high molar absorptivities and fluorescence quantum yields. The use of laser diodes for excitation and photodiodes for detection makes the NIR fluorophores an ideal choice as tracers for various applications. NIR fluorescence immunoassays (NIRFIAs) for disease-related antigens have been developed and optimized in our laboratory during the past few years. NIRFIA can be used in both sandwich and competitive formats. We have successfully adapted the NIRFIA as both a microtiter plate assay and a fiber optic probe. This paper is focussed on the environmental analytical applications of this novel technique. Physical properties of ideal NIR labels and engineering problems of devising remote sensors are discussed.
Step and Flash Imprint Lithography: A Technology Review (2000)

The development of imprint lithography is an attempt by researchers to meet or exceed the size targets outlined in the SIA roadmap for semiconductors, while circumventing the expensive exposure sources and optics required by more conventional next generation lithographies, such as extreme UV, electron projection, and X-ray lithographies. There are promising applications in addition to the semiconductor arena, such as micro-electromechanical devices (MEMs), micro-optics, and patterned storage media. Imprint lithography has the advantage that it uses fundamental fluid displacement principles to define a pattern, rather than i mage reduction with diffraction corrections, but the temperatures required by the more traditional micromolding or hot embossing techniques may present insurmountable obstacles in overlay alignment accuracy, and for applications requiring high throughput. Step and Flash Imprint Lithography (SFIL), being developed primarily at the University of Texas at Austin, overcomes these issues by using a rigid, UV-transparent imprint template, and a bilayer resist scheme composed of an organic planarizing layer and a low viscosity, UV-curable organosilicon solution for imprint imaging. We describe the technology fundamentals here. We demonstrate a durable, low surface energy template release coating, a UV-curable organosilicon etch barrier that cures with low dosage, and the equipment that allows for the high-precision orientation of the template/substrate system necessary for imprint patterning. We have demonstrated printed features as small as 60 nm (not shown), compatibility with metal lift-off processing, functional optical devices including a micropolarizer array, and the ability to pattern high-aspect ratio, sub 0.25 micron features over a non-flat substrate.
Protection from anti-TCR/CD3-induced apoptosis in immature thymocytes by a signal through thymic shared antigen-1/stem cell antigen-2. (1996)

During T cell development in the thymus, the expression of thymic shared antigen-1 (TSA-1)/stem cell antigen-2 (Sca-2), a glycosylphosphatidylinositol (GPI)-anchored differentiation antigen, is developmentally regulated. The expression level of TSA-1 is the highest in most immature CD4- CD8- thymocytes, high in CD4+ CD8+ thymocytes, but barely detectable in mature CD4+ CD8- or CD4- CD8- thymocytes and peripheral T cells. We have previously shown that surface TSA-1 expression in peripheral T cells is induced upon activation and that anti-TSA-1 mAb inhibits the T cell receptor (TCR) signaling pathway in activated T cells. In the present study, we have analyzed a role of TSA-1 in thymic selection events, especially in TCR-mediated apoptosis. In in vitro experiments, anti-TSA-1 blocked anti-CD3-induced cell death of T cell hybridomas. When anti-TSA-1 was injected into newborn mice in vivo together with anti-CD3 epsilon or anti-TCR-beta, TCR/CD3-mediated apoptosis of thymocytes was almost completely blocked. The blockade of apoptosis was defined by the inhibition of, first, the decrease in total number of thymocytes; second, the decrease in percentages of CD4+ CD8+ thymocytes; and third, the induction of DNA fragmentation. However, anti-TSA-1 did not block either steroid- or radiation-induced apoptosis, indicating that a signal via TSA-1 does not inhibit a common pathway of thymocyte apoptosis. Since TCR-mediated apoptosis is pivotal in thymic ontogeny, these results suggest that TSA-1/Sca-2 is an important cell surface molecule regulating the fate of a developing T cell.
Proteasome inhibition causes nigral degeneration with inclusion bodies in rats (2002)

Structural and functional defects in 26/20S proteasomes occur in the substantia nigra pars compacta and may underlie protein accumulation, Lewy body formation and dopaminergic neuronal death in Parkinson's disease. We therefore determined the pathogenicity of proteasomal impairment following stereotaxic unilateral infusion of lactacystin, a selective proteasome inhibitor, into the substantia nigra pars compacta of rats. These animals became progressively bradykinetic, adopted a stooped posture and displayed contralateral head tilting. Administration of apomorphine to lactacystin-treated rats reversed behavioral abnormalities and induced contralateral rotations. Lactacystin caused dose-dependent degeneration of dopaminergic cell bodies and processes with the cytoplasmic accumulation and aggregation of alpha-synuclein to form inclusion bodies. These findings support the notion that failure of the ubiquitin-proteasome system to degrade and clear unwanted proteins is an important etiopathogenic factor in Parkinson's disease.
Synthesis of nanocrystals via microreaction with temperature gradient: towards separation of nucleation and growth (2008)

By utilizing the symmetrical temperature distribution in a tube furnace chamber, a capillary microreactor was designed with the microchannel passing two well-controlled, stable temperatures in steep temperature gradients. The two-temperature microreator, first developed and implemented by this research team, provides an opportunity to separate the nucleation and growth of semiconductor nanocrystals, leading to better control of nucleation and growth kinetics. For the synthesis of CdSe nanocrystals as a model system, we demonstrated the improved size uniformity achieved by the two-temperature approach, confirming the success of the use of high temperature to burst nucleation and low temperature to promote growth.
A Multi-Protocol Approach to Service Discovery and Access in Pervasive Environments (2006)

Pervasive computing environments bring new challenges for client/service interactions due to the heterogeneity of both the interconnected networks and the middleware platforms used. In order for clients to truly benefit from all the networked services embedded into the environment, an innovative solution is required that overcomes both the lack of interoperability of the existing discovery and access protocols, and the limited interconnectivity between the different networks available at a location. This paper introduces the MUSDAC middleware platform that interoperates with existing middleware protocols, and manages the dissemination of service information in dynamic multi-network environments. A generic service is thus provided that enables clients to discover and interact with services in the entire environment A prototype implementation of our platform is further presented, enabling us to demonstrate the flexibility of our approach
Enhanced in vitro induced production of interleukin 10 by peripheral blood mononuclear cells in rheumatoid arthritis is associated with clinical response to methotrexate treatment. (2001)

Enhanced ex vivo LPS induced IL-10 production by PBMC of patients with RA is associated with a favorable therapeutic response to MTX treatment, whereas reduced production coincides more closely with disease deterioration or insufficient response. This may reflect both disease outcome upon treatment and/or the mode of the antiinflammatory action of MTX in RA. Because the LPS--but not the PHA--induced ex vivo IL-10 production by PBMC was stimulated by MTX in vivo, monocytes seem to be the prominent target cells for this drug mediated antiinflammatory cytokine regulation.
Third complementarity‐determining region of mutated VH immunoglobulin genes contains shorter V, D, J, P, and N components than non‐mutated genes (2001)

The third complementarity-determining region (CDR3) of immunoglobulin variable genes for the heavy chain (VH) has been shown to be shorter in length in hypermutated antibodies than in non-hypermutated antibodies. To determine which components of CDR3 contribute to the shorter length, and if there is an effect of age on the length, we analysed 235 cDNA clones from human peripheral blood of VH6 genes rearranged to immunoglobulin M (IgM) constant genes. There was similar use of diversity (D) and joining (JH) gene segments between clones from young and old donors, and there was similar use of D segments among the mutated and non-mutated heavy chains. However, in the mutated heavy chains, there was increased use of shorter JH4 segments and decreased use of longer JH6 segments compared to the non-mutated proteins. The overall length of CDR3 did not change with age within the mutated and non-mutated categories, but was significantly shorter by three amino acids in the mutated clones compared to the non-mutated clones. Analyses of the individual components that comprise CDR3 indicated that they were all shorter in the mutated clones. Thus, there were more nucleotides deleted from the ends of VH, D, and JH gene segments, and fewer P and N nucleotides added. The results suggest that B cells bearing immunoglobulin receptors with shorter CDR3s have been selected for binding to antigen. A smaller CDR3 may allow room in the antibody binding pocket for antigen to interact with CDRs 1 and 2 as well, so that as the VDJ gene undergoes hypermutation, substitutions in all three CDRs can further contribute to the binding energy.
Drug-specific sites of topoisomerase II DNA cleavage in Drosophila chromatin: heterogeneous localization and reversibility. (1996)

DNA cleavage stimulated by different topoisomerase II inhibitors shows in vitro a characteristic sequence specificity. Since chromatin structure and genome organization are expected to influence drug-enzyme interactions and repair of drug-induced DNA lesions, we investigated topoisomerase II DNA cleavage sites stimulated by teniposide (VM-26), 4-demethoxy-3'-deamino-3'-hydroxy-4'-epi-doxorubicin (dh-EPI, a doxorubicin derivative), 4'-(9-acridinylamino)-methanesulfon-m-anisidide, and amonafide in the histone gene locus and satellite III DNA of Drosophila cells with Southern blottings and genomic sequencing by primer extension. VM-26 stimulated cleavage in the satellite III DNA, whereas the other studied drugs did not. All four drugs stimulated cleavage in the histone gene cluster, but they yielded drug-specific cleavage intensity patterns. Cleavage sites by dh-EPI and VM-26 were sequenced in the histone H2A gene promoter and were shown to be distinct. DNA cleavage analysis in cloned DNA fragments with Drosophila topoisomerase II showed that drugs stimulated the same sites in vivo and in vitro. Strand cuts were in vivo staggered by 4 bases, and base sequences at major dh-EPI and VM-26 sites completely agreed with known in vitro drug sequence specificities. Moreover, DNA cleavage reverted faster in the satellite III than in the histone repeats. While stimulating similar levels of DNA breakage in bulk genomic DNA, dh-EPI and VM-26 markedly differed for cleavage extent and reversibility in specific chromatin loci. The results demonstrate a high heterogeneity in the localization, extent, and reversibility of drug-stimulated DNA cleavage in the chromatin of living cells.
Reversion of the invasive phenotype of transformed human fibroblasts by anti-messenger oligonucleotide inhibition of urokinase receptor gene expression. (1995)

The receptors for urokinase plasminogen activator were studied in both normal human fibroblasts (WI-38 cells) and their SV40-transformed counterpart (VA-13 cells). We have shown that transformed cells expose 10 times more urokinase plasminogen activator receptors (u-PAR) than normal cells. By cross-linking aliquots of cell lysates with the aminoterminal fragment of the A chain of u-PA, containing the receptor-binding sequence, we have observed a u-PAR concentration at focal contacts in both cell lines. Only transformed cells were able to efficiently invade the basement membrane Matrigel. Switching off the receptor gene expression by the anti-messenger oligodeoxynucleotides strategy abolished the invasive properties of transformed cells. The anti-messenger oligodeoxynucleotide sequence we have designed inhibited the u-PAR gene expression, lowering both the receptor and the receptor mRNA. This indicates that overexpression of u-PAR gene is itself responsible for invasivity of transformed fibroblasts in our cell model system and that antisense compound therapy may prove to be of clinical interest in the control of cancer spreading.
Polar substituent effects in gas-phase Lewis acid-base equilibriums. I. Insrinsic basicity of amines (1968)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTPolar substituent effects in gas-phase Lewis acid-base equilibriums. I. Insrinsic basicity of aminesPeter Love, Ronald B. Cohen, and Robert W. TaftCite this: J. Am. Chem. Soc. 1968, 90, 10, 2455–2462Publication Date (Print):May 1, 1968Publication History Published online1 May 2002Published inissue 1 May 1968https://pubs.acs.org/doi/10.1021/ja01012a001https://doi.org/10.1021/ja01012a001research-articleACS PublicationsRequest reuse permissionsArticle Views331Altmetric-Citations27LEARN 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
Minimal Residual Disease in Hairy Cell Leukemia Patients Assessed by Clone-Specific Polymerase Chain Reaction (2006)

Cladribine induces long-term complete remission in hairy cell leukemia (HCL) patients but does not clear minimal residual disease (MRD) according to high-sensitivity PCR assays. To quantify MRD in patients after anti-CD22 recombinant immunotoxin BL22 and other agents, we used a relative quantitative PCR (RQ-PCR) assay using a primer and probe, both patient specific for the immunoglobulin heavy chain rearrangement. Using this method, we were able to detect one Bonna 12 HCL cell in either 10(6) Jurkat cells or in 10(6) normal mononuclear cells. We studied 84 samples from 10 patients, taken before or after treatment with BL22 and other agents. Patient-specific RQ-PCR was much more sensitive than flow cytometry, which in turn was (as recently reported) more sensitive than PCR using consensus primers. RQ-PCR was positive in 62 of 62 (100%) flow-positive samples in 10 patients and in 20 of 22 (91%) flow-negative samples in six patients. The relative level of MRD as quantified by RQ-PCR correlated with disease status and remission. Thus, patient-specific RQ-PCR is the most sensitive test for MRD in HCL patients and could be used to determine maximal response in patients obtaining multiple cycles of nonmyelotoxic biological treatment for this disease.
MIMO Ground-Radiation Antennas Using a Novel Closed-Decoupling-Loop for 5G Applications (2020)

This paper investigates the design of a compact multiple-input multiple-output (MIMO) ground-radiation antenna system for 5G terminal devices. Ground-radiation antennas are small loop-type resonators that can excite the ground plane as radiators while having advantages of small size and convenient tunability, but their compact MIMO systems remain as unsolved issues. In this study, a novel and straightforward decoupling technique based on a closed-decoupling-loop is presented for MIMO applications in the first of its kind. The proposed closed-decoupling loop can be viewed as a coupling transformer between two antenna elements by acting as a half-wavelength loop-type resonator and by introducing a current null at its center; in this way, a tremendous isolation improvement is accomplished even though the distance between two antennas is only 1 mm. Therefore, a compact 2 x 2 MIMO ground-radiation antenna system and its 8 × 8 MIMO system are demonstrated for 5G applications. Both simulation and measurement are taken to validate the proposed decoupling technique and the compact MIMO ground-radiation antenna system.